@article {pmid40264918,
year = {2025},
author = {Ghosh, N and Bellasea, S and Li, H and Olszewski, AJ and Bryan, L and Danilov, A and Smith, S and LeBlanc, M and Friedberg, JW},
title = {SWOG 2308: Randomized Phase III Study of Mosunetuzumab Versus Rituximab for Low-Tumor Burden Follicular Lymphoma.},
journal = {JCO oncology advances},
volume = {2},
number = {1},
pages = {e2500037},
pmid = {40264918},
issn = {2994-9750},
}

@article {pmid40264148,
year = {2025},
author = {Montaño, MA and Chen, Y and Saldarriaga, EM and Thuo, N and Kiptinness, C and Stergachis, A and Mugambi, ML and Ngure, K and Ortblad, KF and Sharma, M},
title = {Willingness to pay for HIV pre- and post-exposure prophylaxis services delivered via an online pharmacy in Kenya.},
journal = {BMC health services research},
volume = {25},
number = {1},
pages = {576},
pmid = {40264148},
issn = {1472-6963},
support = {INV-037646/GATES/Gates Foundation/United States ; INV-037646/GATES/Gates Foundation/United States ; INV-037646/GATES/Gates Foundation/United States ; INV-037646/GATES/Gates Foundation/United States ; INV-037646/GATES/Gates Foundation/United States ; INV-037646/GATES/Gates Foundation/United States ; INV-037646/GATES/Gates Foundation/United States ; INV-037646/GATES/Gates Foundation/United States ; INV-037646/GATES/Gates Foundation/United States ; INV-037646/GATES/Gates Foundation/United States ; K99/R00 MH121166/MH/NIMH NIH HHS/United States ; },
mesh = {Humans ; Kenya ; *HIV Infections/prevention & control ; Male ; *Pre-Exposure Prophylaxis/economics ; Female ; Adult ; Surveys and Questionnaires ; *Post-Exposure Prophylaxis/economics ; *Pharmaceutical Services, Online/economics ; Young Adult ; Middle Aged ; Adolescent ; *Financing, Personal ; },
abstract = {BACKGROUND: HIV pre- and post-exposure prophylaxis (PrEP/PEP) provision via online pharmacies could expand reach of HIV prevention in Eastern and Southern Africa, but designing sustainable delivery models will require assessing the amount potential users are willing to pay for online PrEP/PEP provision.

METHODS: We administered willingness to pay (WTP) questionnaires to both potential online PrEP users and current online PrEP/PEP users in Nairobi, Kenya using a stated preference approach to measure the amount participants were willing to pay for PrEP/PEP service delivery components. Participants ≥ 18 years were recruited via banner ads on an online pharmacy website on pages displaying sexual health products. We used multivariable gamma regression models to assess characteristics associated with differences in mean WTP for a 30-day PrEP or 28-day PEP course (including HIV self-testing, remote clinical consultation, drugs, and delivery fees).

RESULTS: From May 2022 and December 2023, 1,512 participants completed WTP questionnaires: 772 potential online PrEP users and 740 current online PrEP/PEP users. Most participants (98.3%, 1486/1,512) were willing to pay some amount for online PrEP services. For a one-month PrEP supply, potential online PrEP users were willing to pay 1388 KSH ($11.77 USD) and current online PrEP/PEP users were willing to pay 1271.2 KSH ($10.77 USD) on average. Most current online PrEP/PEP users (81.4%, 602/740) were also willing to pay for online PEP services; for a 28-day PEP supply, they were willing to pay 812.9 KSH ($6.89 USD) on average. Among potential online PrEP users, male sex, current enrollment in school, high income, and a history of online pharmacy purchases were associated with higher WTP for PrEP. Among current online PrEP/PEP users, higher income and prior online pharmacy purchases were associated with higher WTP for PrEP, and older age (> 24) and prior online pharmacy purchases were associated with higher WTP for PEP.

CONCLUSION: Most potential and current online PrEP/PEP users in Nairobi were willing to pay for online pharmacy-based PrEP/PEP and demonstrated similar WTP. Providing PrEP/PEP through online pharmacies may sustainably expand coverage of these HIV prevention services.},
}

Humans
Kenya
*HIV Infections/prevention & control
Male
*Pre-Exposure Prophylaxis/economics
Female
Adult
Surveys and Questionnaires
*Post-Exposure Prophylaxis/economics
*Pharmaceutical Services, Online/economics
Young Adult
Middle Aged
Adolescent
*Financing, Personal

@article {pmid40262193,
year = {2025},
author = {Shigesi, N and Harris, HR and Fang, H and Ndungu, A and Lincoln, MR and , and , and Cotsapas, C and Knight, J and Missmer, SA and Morris, AP and Becker, CM and Rahmioglu, N and Zondervan, KT},
title = {The phenotypic and genetic association between endometriosis and immunological diseases.},
journal = {Human reproduction (Oxford, England)},
volume = {},
number = {},
pages = {},
doi = {10.1093/humrep/deaf062},
pmid = {40262193},
issn = {1460-2350},
support = {RG2031//Wellbeing of Women UK/ ; 101017562//EU Horizon 2020 funded project FEMaLe/ ; 32170663//National Natural Science Foundation of China/ ; },
abstract = {STUDY QUESTION: Is there an increased risk of immunological diseases among endometriosis patients, and does a shared genetic basis contribute to this risk?

SUMMARY ANSWER: Endometriosis patients show a significantly increased risk of autoimmune, autoinflammatory, and mixed-pattern diseases, including rheumatoid arthritis, multiple sclerosis, coeliac disease, osteoarthritis, and psoriasis, with genetic correlations between endometriosis and osteoarthritis, rheumatoid arthritis, and multiple sclerosis, and a potential causal link to rheumatoid arthritis.

WHAT IS KNOWN ALREADY: The epidemiological evidence for an increased risk of immunological diseases among women with endometriosis is limited in scope and has varied in robustness due to the opportunity for biases. The presence of a biological basis for increased comorbidity across immunological conditions has not been investigated. Here we investigate the phenotypic and genetic association between endometriosis and 31 immune conditions in the UK Biobank.

STUDY DESIGN, SIZE, DURATION: Phenotypic analyses between endometriosis and immune conditions (17 classical autoimmune, 10 autoinflammatory, and 4 mixed-pattern diseases) were conducted using two approaches (8223 endometriosis, 64 620 immunological disease cases): (i) retrospective cohort study design to incorporate temporality between diagnoses and (ii) cross-sectional analysis for simple association. Genome-wide association studies (GWAS) and meta-analyses for those immune conditions that showed phenotypic association with endometriosis (1493-77 052 cases) were conducted.

Comprehensive phenotypic association analyses were conducted in females in the UK Biobank. GWAS for immunological conditions were conducted in females-only and sex-combined study populations in UK Biobank and meta-analysed with existing largest available GWAS results. Genetic correlation and Mendelian randomization (MR) analyses were conducted to investigate potential causal relationships. Those immune conditions with significant genetic correlation with endometriosis were included in multi-trait analysis of GWAS to boost discovery of novel and shared genetic variants. These shared variants were functionally annotated to identify affected genes utilizing expression quantitative trait loci (eQTL) data from GTEx and eQTLGen databases. Biological pathway enrichment analysis was conducted to identify shared underlying biological pathways.

In both retrospective cohort and cross-sectional analyses, endometriosis patients were at significantly increased (30-80%) risk of classical autoimmune (rheumatoid arthritis, multiple sclerosis, coeliac disease), autoinflammatory (osteoarthritis), and mixed-pattern (psoriasis) diseases. Osteoarthritis (genetic correlation (rg) = 0.28, P = 3.25 × 10-15), rheumatoid arthritis (rg = 0.27, P = 1.5 × 10-5) and multiple sclerosis (rg = 0.09, P = 4.00 × 10-3) were significantly genetically correlated with endometriosis. MR analysis suggested a causal association between endometriosis and rheumatoid arthritis (OR = 1.16, 95% CI = 1.02-1.33). eQTL analyses highlighted genes affected by shared risk variants, enriched for seven pathways across all four conditions, with three genetic loci shared between endometriosis and osteoarthritis (BMPR2/2q33.1, BSN/3p21.31, MLLT10/10p12.31) and one with rheumatoid arthritis (XKR6/8p23.1).

We conducted the first female-specific GWAS analyses for immune conditions. Given the novelty of these analyses, the sample sizes from which results were derived were limited compared to sex-combined GWAS meta-analyses, which limited the power to use female-specific summary statistics to uncover the shared genetic basis with endometriosis in follow-up analyses. Secondly, the 39 genome-wide significant endometriosis-associated variants used as instrumental variables in the MR analysis explained approximately 5% of disease variation, which may account for the nominal or non-significant MR results.

Endometriosis patients have a moderately increased risk for osteoarthritis, rheumatoid arthritis, and to a lesser extent, multiple sclerosis, due to underlying shared biological mechanisms. Clinical implications primarily involve the need for increased awareness and vigilance. The shared genetic basis opens up opportunities for developing new treatments or repurposing therapies across these conditions.

We thank all the UK Biobank and 23andMe participants. Part of this research was conducted using the UK Biobank Resource under Application Number 9637. N.R. was supported by a grant from the Wellbeing of Women UK (RG2031) and the EU Horizon 2020 funded project FEMaLe (101017562). A.P.M. was supported in part by Versus Arthritis (grant 21754). H.F. was supported by the National Natural Science Foundation of China (grant 32170663). N.R., S.A.M., and K.T.Z. were supported in part by a grant from CDMRP DoD PRMRP (W81XWH-20-PRMRP-IIRA). K.T.Z. and C.M.B. reported grants in 3 years prior, outside the submitted work, from Bayer AG, AbbVie Inc., Volition Rx, MDNA Life Sciences, PrecisionLife Ltd., and Roche Diagnostics Inc. S.A.M. reports grants in the 3 years prior, outside this submitted work, from AbbVie Inc. N.R. is a consultant for Endogene.bio, outside this submitted work. The other authors have no conflicts of interest to declare.

TRIAL REGISTRATION NUMBER: N/A.},
}

@article {pmid40261872,
year = {2025},
author = {Unsworth, M and Fabens, I and Setswe, G and Moyo, K and Pienaar, J and Makhele, C and Phohole, M and Igaba, N and Hlongwane, S and Sardini, M and Dong, T and Sharma, M and Tweya, H and Ndebele, F and Holec, M and Feldacker, C},
title = {Expanding two-way texting for post-operative follow-up: A cost analysis of the implementation and scale-up in routine voluntary medical male circumcision settings in South Africa.},
journal = {PLOS global public health},
volume = {5},
number = {4},
pages = {e0004049},
pmid = {40261872},
issn = {2767-3375},
support = {P30 AI027757/AI/NIAID NIH HHS/United States ; R01 NR019229/NR/NINR NIH HHS/United States ; },
abstract = {Up to 98% of adult voluntary medical male circumcision (VMMC) clients heal without adverse events (AEs) in South Africa and in the sub-Saharan Africa region. Yet, all clients in South Africa are required to attend in-person reviews, creating added effort for providers and clients. A randomized controlled trial (RCT) using our fee-free, open-source, two-way texting (2wT) approach showed that males could independently monitor their healing with nurse-led telehealth support. 2wT was more cost-effective than routine visits for quality post-operative monitoring. The objectives of this study were:1) assess the additive cost of 2wT vs. standard of care (SoC) during a stepped wedge design (SWD) expansion trial; 2) determine the cost of augmenting 2wT implementation with dedicated personnel during peak VMMC periods; and 3) estimate the cost savings of 2wT from the payer perspective if scaled in routine settings. Data were collected from routine financial reports and complemented by previous RCT time-motion estimates. We conducted activity-based costing of SWD and peak season periods. Sensitivity analysis to estimates 2wT costs at scale. Data included 6,842 males; 2,586 (38%) opted for 2wT. 2wT participants attended an average of zero in-person visits; SoC males had an average of 2 in-person visits. Under 2wT, quality care improved: AE ascertainment increased while loss to follow-up decreased. Given a VMMC population of 10,000 adults, scenario analysis suggests that: 1) 2wT becomes cost neutral with 45% 2wT enrollment; 2) 2wT saves $0.29/client with 60% 2wT enrollment; and 3) 2wT saves $0.46/client with 80% 2wT enrollment. When scaled, 2wT appears to significantly reduce healthcare system costs while improving the quality of post-operative care without additional client costs. Further scale-up of 2wT for eligible males across VMMC and other post-operative contexts in South Africa would likely increase cost savings while dramatically reducing the burden of in-person visits on patients and clinics.},
}

@article {pmid40261064,
year = {2025},
author = {Žuštra, A and Leonard, VR and Holland, LA and Hu, JC and Mu, T and Holland, SC and Wu, LI and Begnel, ER and Ojee, E and Chohan, BH and Richardson, BA and Kinuthia, J and Wamalwa, D and Slyker, J and Lehman, DA and Gantt, S and Lim, ES},
title = {Longitudinal dynamics of the nasopharyngeal microbiome in response to SARS-CoV-2 Omicron variant and HIV infection in Kenyan women and their children.},
journal = {mSystems},
volume = {},
number = {},
pages = {e0156824},
doi = {10.1128/msystems.01568-24},
pmid = {40261064},
issn = {2379-5077},
abstract = {UNLABELLED: The nasopharynx and its microbiota are implicated in respiratory health and disease. The interplay between viral infection and the nasopharyngeal microbiome is an area of increased interest. The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of the coronavirus disease 2019 pandemic, on the nasopharyngeal microbiome among individuals living with HIV is not fully characterized. Here, we describe the nasopharyngeal microbiome before, during, and after SARS-CoV-2 infection in a longitudinal cohort of Kenyan women (21 living with HIV and 14 HIV-uninfected) and their children (18 HIV-exposed, uninfected and 7 HIV-unexposed, uninfected) between September 2021 and March 2022. We show using genomic epidemiology that mother and child dyads were infected with the same strain of the SARS-CoV-2 Omicron variant that spread rapidly across Kenya. We used metagenomic sequencing to characterize the nasopharyngeal microbiome of 20 women and children infected with SARS-CoV-2, six children negative for SARS-CoV-2 but experiencing respiratory symptoms, and 34 timepoint-matched SARS-CoV-2-negative mothers and children. Since individuals were sampled longitudinally before and after SARS-CoV-2 infection, we could characterize the short- (within a week of infection) and longer- (average of 38 days post-infection) term impact of SARS-CoV-2 infection on the nasopharyngeal microbiome. We found that mothers and children had significantly different microbiome composition and bacterial load (P-values < 0.0001). In both mothers and children, the nasopharyngeal microbiome did not differ before and after SARS-CoV-2 infection, regardless of HIV exposure status. Our results indicate that the nasopharyngeal microbiome is resilient to SARS-CoV-2 infection and was not significantly modified by HIV.

IMPORTANCE: The nasopharyngeal microbiome plays an important role in human health. The degree of impact that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has on the nasopharyngeal microbiome varies among studies and may be influenced by diverse SARS-CoV-2 variants and variations in the microbiome between individuals. Our results show that the nasopharyngeal microbiome was not altered substantially by SARS-CoV-2 infection nor by HIV infection in mothers or HIV exposure in children. Our findings highlight the resilience of the nasopharyngeal microbiome after SARS-CoV-2 infection. These findings advance our understanding of the nasopharyngeal microbiome and its interactions with viral infections.},
}

@article {pmid40261015,
year = {2025},
author = {Radford, CE and Bloom, JD},
title = {Comprehensive maps of escape mutations from antibodies 10-1074 and 3BNC117 for Envs from two divergent HIV strains.},
journal = {Journal of virology},
volume = {},
number = {},
pages = {e0019525},
doi = {10.1128/jvi.00195-25},
pmid = {40261015},
issn = {1098-5514},
abstract = {Antibodies capable of neutralizing many strains of HIV are being explored as prophylactic and therapeutic agents, but viral escape mutations pose a major challenge. Efforts have been made to experimentally define the escape mutations from specific antibodies in specific viral strains, but it remains unclear how much the effects of mutations on neutralization differ among HIV strains. Here, we use pseudovirus deep mutational scanning to comprehensively map escape mutations from the V3 loop targeting antibody 10-1074 and the CD4-binding site targeting antibody 3BNC117 for both a clade A (BF520) and a clade B (TRO.11) HIV Envelope (Env). Mutations that escape neutralization by antibody 10-1074 are largely similar for the two Envs, but mutations that escape 3BNC117 differ greatly between Envs. Some differences in the effects of mutations on escape between Envs can be explained by strain-to-strain variation in mutational tolerance or potential N-linked glycosylation motifs, but other mutations have different effects on escape for unclear reasons. Overall, the extent to which measurements of mutational effects on antibody neutralization can be generalized across HIV strains differs among antibodies 10-1074 and 3BNC117.IMPORTANCEBroadly neutralizing antibodies are promising candidates as prophylactics and therapeutics for HIV. This study uses pseudoviruses to map all escape mutations for antibodies 10-1074 and 3BNC117 for the Envelope proteins from two different HIV strains. These maps can inform analyses of viral mutations observed in clinical trials and help understand how the escape mutations from these antibodies differ across HIV strains.},
}

@article {pmid40260855,
year = {2025},
author = {Jatt, LP and Mgodi, NM and Buchbinder, SP and Gray, GE and Kublin, JG},
title = {An HIV Vaccine in the Era of Twice-Yearly Lenacapavir for PrEP - Essential or Irrelevant?.},
journal = {The New England journal of medicine},
volume = {392},
number = {16},
pages = {1561-1563},
doi = {10.1056/NEJMp2415893},
pmid = {40260855},
issn = {1533-4406},
}

@article {pmid40259184,
year = {2025},
author = {Zelaya, DG and Janssen, T and Windes, B and Wheeler, DP and Fields, SD and Beauchamp, G and Kahler, CW and Wilton, L and Mayer, KH},
title = {The Association of Positive Intersectionality Latent Classes with Psychosocial Factors and PrEP Outcomes in Black Men Who Have Sex with Men (HPTN 073).},
journal = {Journal of racial and ethnic health disparities},
volume = {},
number = {},
pages = {},
pmid = {40259184},
issn = {2196-8837},
support = {K23AA030339/AA/NIAAA NIH HHS/United States ; K01AA026335/AA/NIAAA NIH HHS/United States ; AA019072/AA/NIAAA NIH HHS/United States ; P30AI042853//Division of Intramural Research, National Institute of Allergy and Infectious Diseases/ ; UM1AI068619//Division of Intramural Research, National Institute of Allergy and Infectious Diseases/ ; UM1AI069412//Division of Intramural Research, National Institute of Allergy and Infectious Diseases/ ; },
abstract = {Experiences of discrimination and HIV risk in Black men who have sex with men (MSM) need to be examined from the perspective of strength and resilience and not just risk. Scholars have theorized that a strong connection with one's sociocultural identities may increase individuals' ability to cope with discrimination which has been related to positive health outcomes. Scholars have coined the term positive intersectionality to refer to how one's stigmatized identity(ies) can be used to draw strength and create a positive sense of self. The current study is a secondary data analysis of a study of 225 Black MSM. We utilized Latent Class Analysis to determine profiles of positive intersectionality measured by indicators of racial/ethnic identity, having an integrated sexual orientation and racial/ethnic identity, and levels of internalized homophobia. Fit indices suggested a five-latent class solution: low positive intersectionality (n = 3), ambivalent positive intersectionality (n = 19), moderate positive intersectionality (n = 66), salient/high positive intersectionality (n = 124), and conflict(ed) positive intersectionality (n = 13). Differences were found across classes on key outcomes, broadly individuals in classes with more positive intersectionality tended to report more positive psychosocial outcomes (i.e., more social support and less depression) than those in classes with lower positive intersectionality. Regarding PrEP outcomes, adherence (examined via a biomarker) was highest among those reporting ambivalent or conflict positive intersectionality compared to those with low positive intersectionality. Our findings underscore the need for the development of strengths-based and culturally tailored interventions may help to improve well-being for Black MSM.},
}

@article {pmid40255392,
year = {2025},
author = {Manghisi, B and Cotilli, G and Fedele, M and Perfetti, P and Terruzzi, E and Verga, L and Borin, LM and Carrer, A and Fumagalli, M and Ferrari, MB and Moretti, A and Rona, R and Benini, A and Vergnano, B and Palumbo, G and Zincone, A and Maglia, O and Scollo, C and Steidl, C and Iovino, L and Balduzzi, A and Piazza, R and Gambacorti-Passerini, C and Parma, M and Aroldi, A},
title = {Case Report: Successful use of emapalumab in adult B-cell acute lymphoblastic leukemia experiencing severe neurotoxicity and hemophagocytic lymphohistiocytosis-like features after CAR-T cell therapy.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1563736},
pmid = {40255392},
issn = {1664-3224},
mesh = {Adult ; Humans ; *Antibodies, Monoclonal/therapeutic use ; *Antibodies, Monoclonal, Humanized/therapeutic use ; Cytokine Release Syndrome ; *Immunotherapy, Adoptive/adverse effects ; *Lymphohistiocytosis, Hemophagocytic/etiology/drug therapy/diagnosis ; *Neurotoxicity Syndromes/etiology/drug therapy/diagnosis ; *Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy/immunology ; Receptors, Chimeric Antigen ; Treatment Outcome ; },
abstract = {Chimeric antigen receptor (CAR)-T cell therapy is a powerful adoptive immunotherapy associated with significant toxicity, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). As CAR-T usage expands, hyperinflammatory toxicities resembling hemophagocytic lymphohistiocytosis (HLH) syndrome are increasingly recognized. Immune effector cell-associated HLH-like syndrome (IEC-HS) describes HLH-like symptoms attributable to CAR-T cell therapy, often presenting as CRS resolves. Treatments for IEC-HS are adapted from primary HLH, including corticosteroids, the recombinant human interleukin (IL)-1 receptor antagonist anakinra and the Janus Kinase inhibitor ruxolitinib. Emapalumab, an anti-IFN-γ antibody, is promising but underexplored in adult IEC-HS cases. We report an adult B-cell acute lymphoblastic leukemia (B-ALL) patient treated with brexucabtagene autoleucel (brexu-cel). The patient developed CRS, refractory neurotoxicity, and IEC-HS with worsening multiorgan failure and hyperinflammatory markers. Treatment included tocilizumab, high-dose corticosteroids, anakinra, siltuximab, and ruxolitinib. Despite aggressive management, hyperinflammation and neurotoxicity persisted. Emapalumab was initiated on day +11, resulting in normalization of the biochemical parameters and full neurological recovery by day +21. The patient recovered from IEC-HS and underwent allogeneic stem cell transplantation. This case highlights the role of emapalumab in managing refractory IEC-HS and persistent neurotoxicity in adults, underscoring the need for targeted interventions in severe CAR-T complications.},
}

Adult
Humans
*Antibodies, Monoclonal/therapeutic use
*Antibodies, Monoclonal, Humanized/therapeutic use
Cytokine Release Syndrome
*Immunotherapy, Adoptive/adverse effects
*Lymphohistiocytosis, Hemophagocytic/etiology/drug therapy/diagnosis
*Neurotoxicity Syndromes/etiology/drug therapy/diagnosis
*Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy/immunology
Receptors, Chimeric Antigen
Treatment Outcome

@article {pmid40253488,
year = {2025},
author = {Li, X and Mamouni, K and Zhao, R and Bai, L and Chen, Y and Wu, Y and Xie, ZR and Sautto, GA and Liu, D and Bowen, NJ and Danaher, A and Li, D and Cook, N and Grayson, S and Zhu, J and Coleman, IM and Nelson, PS and Bao, Q and Zhou, J and Osunkoya, AO and Kucuk, O and Gera, L and Wu, D},
title = {Novel Skp1 inhibitor has potent preclinical efficacy against castration-resistant prostate cancer.},
journal = {British journal of cancer},
volume = {},
number = {},
pages = {},
pmid = {40253488},
issn = {1532-1827},
support = {R01CA256058//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; R42CA217491//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; R01 CA266452/CA/NCI NIH HHS/United States ; R21CA277368//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; P50CA097186//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; R50CA274336//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; R01 CA266452/CA/NCI NIH HHS/United States ; R21CA277368//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; P50CA097186//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; },
abstract = {BACKGROUND: Metastatic, castration-resistant prostate cancer (mCRPC) directly contributes to the mortality and morbidity of prostate cancer. It is imperative to identify new molecular targets and discover effective therapeutic agents against lethal mCRPC.

METHODS: The anticancer activities and mechanism of action of the small-molecule lead compound were investigated in preclinical models of human prostate cancer. Immunohistochemistry was employed to determine the expression of S-phase kinase-associated protein 1 (Skp1) in human prostate tissues.

RESULTS: GH501 demonstrates nanomolar potency in the NCI-60 human cancer cell panel and multiple mCRPC cell lines with diverse genetic backgrounds, including those resistant to androgen deprivation therapy drugs. Mechanistically, GH501 may bind Skp1 and disrupt the physical interaction between Skp1 and S-phase kinase-associated protein 2 (Skp2) within the Skp1-Cullin1-F-box protein ubiquitin ligase complexes (SCF), thereby affecting multiple oncogenic signals implicated in mCRPC progression, including p21, p27, β-catenin, cyclin D1, enhancer of zeste homolog 2 (EZH2), c-Myc, and survivin. GH501 exhibits excellent in vitro and in vivo safety pharmacology, and GH501 monotherapy effectively inhibits the in vivo growth of cell- and patient-derived xenografts in intraosseous and subcutaneous models. Skp1 expression is significantly increased in human prostate cancer specimens.

CONCLUSION: These results indicate that interrupting Skp1-Skp2 interaction is an effective approach to target mCRPC and warrant further preclinical development of GH501 as a promising therapeutic candidate.},
}

@article {pmid40251235,
year = {2025},
author = {Dimopoulou, O and Fuller, H and Richmond, RC and Bouras, E and Hayes, B and Dimou, N and Murphy, N and Brenner, H and Gsur, A and Le Marchand, L and Moreno, V and Pai, RK and Phipps, AI and Um, CY and van Duijnhoven, FJB and Vodicka, P and Martin, RM and Platz, EA and Gunter, MJ and Peters, U and Lewis, SJ and Cao, Y and Tsilidis, KK},
title = {Mendelian randomization study of sleep traits and risk of colorectal cancer.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {13478},
pmid = {40251235},
issn = {2045-2322},
support = {C18281/A29019/CRUK_/Cancer Research UK/United Kingdom ; },
mesh = {Humans ; *Mendelian Randomization Analysis ; *Colorectal Neoplasms/genetics/epidemiology ; Male ; Female ; *Sleep/genetics ; Genome-Wide Association Study ; Risk Factors ; Polymorphism, Single Nucleotide ; Genetic Predisposition to Disease ; Circadian Rhythm/genetics ; Sleep Initiation and Maintenance Disorders/genetics ; },
abstract = {A potential association of endogenous circadian rhythm disruption with risk of cancer development has been suggested, however, epidemiological evidence for the association of sleep traits with colorectal cancer (CRC) is limited and often contradictory. Here we investigated whether genetically predicted chronotype, insomnia and sleep duration are associated with CRC risk in males, females and overall and according to CRC anatomical subsites using Mendelian randomization (MR). The two-sample inverse variance weighted (IVW) method was applied using summary-level data in up to 58,221 CRC cases and 67,694 controls and genome-wide association data of genetic variants for self-reported sleep traits. Secondary analyses using alternative instruments and sensitivity analyses assessing potential violations of MR assumptions were conducted. Genetically predicted morning preference was associated with 13% lower risk of CRC in men (ORIVW = 0.87, 95% CI = 0.78, 0.97, P = 0.01), but not in women or in both sexes combined. Τhis association remained consistent in some, but not all, sensitivity analyses and was very similar for colon and rectal cancer. There was no evidence of an association for any other sleep trait. Overall, this study provides little to no evidence of an association between genetically predicted sleep traits and CRC risk.},
}

Humans
*Mendelian Randomization Analysis
*Colorectal Neoplasms/genetics/epidemiology
Male
Female
*Sleep/genetics
Genome-Wide Association Study
Risk Factors
Polymorphism, Single Nucleotide
Genetic Predisposition to Disease
Circadian Rhythm/genetics
Sleep Initiation and Maintenance Disorders/genetics

@article {pmid40250799,
year = {2025},
author = {Karvonen, KL and Anunwah, E and Gilmore, S and Griffiths-Randolph, U and Karvonen, KA and Moore, D and Miller, K and Overall, J and Wooten, L and Afulani, PA},
title = {Gaps, Successes, and Opportunities Related to Social Drivers of Health from the Perspectives of Black Preterm Infant Caregivers: A Qualitative Study.},
journal = {The Journal of pediatrics},
volume = {},
number = {},
pages = {114598},
doi = {10.1016/j.jpeds.2025.114598},
pmid = {40250799},
issn = {1097-6833},
abstract = {OBJECTIVE: To identify Black preterm infant caregiver experiences and institutional priorities regarding screening and addressing social drivers of health (SDH).

STUDY DESIGN: In the Centering Black Preterm Infant Caregiver Priorities (CENTER & CARE) study, Black female researchers conducted semi-structured interviews in 2024 with Black caregivers of preterm infants born in the San Francisco Bay Area of California. Transcripts were coded using a book generated from an interview guide and the resulting data were analyzed using thematic analysis. Themes were generated and refined through discussion.

RESULTS: Twenty socio-demographically diverse caregivers participated. Five themes were identified: (1) financial insecurity and inadequate access to resources for everyday social needs contribute negatively to caregiver and child health and well-being; (2) a trusted provider who takes a personal approach to screening and addressing SDH is needed in medical settings; (3) inequitably distributed, fragmented, and disorganized medical and social support systems in the transition to home period are burdensome and a source of stress; (4) community-based organizations centering Black families holistically address SDH and promote social well-being and connectedness; and (5) state and federal legislation, policies, and programs are critical opportunities to address SDH.

CONCLUSION: SDH are a significant source of stress for caregivers after preterm birth, and there are opportunities across state and federal legislative policies, community-based organizations, medical systems, and connections across the systems to address them.},
}

@article {pmid40249911,
year = {2025},
author = {Perales, MA and Riches, M and He, N and Martens, MJ and Chemaly, RF and Dandoy, CE and Hill, JA and Díaz, MA and Hashmi, S and Prockop, SE and Lazarus, HM and Beitinjaneh, AM and Hildebrandt, GC and Auletta, JJ and Szabolcs, P},
title = {Delayed T cell recovery after hematopoietic cell transplantation is associated with decreased overall survival in adults.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2024015288},
pmid = {40249911},
issn = {2473-9537},
abstract = {Allogeneic hematopoietic cell transplantation (alloHCT) can provide curative treatment for hematologic malignancies but is associated with prolonged lymphopenia that may contribute to an increased risk of infection and relapse, resulting in decreased survival. We hypothesized that patients with rapid and robust CD4 T and B cell recovery have improved survival and decreased treatment-related mortality (TRM). 2089 patients were included who underwent first alloHCT for AML/ALL/MDS from 2008 to 2019 reported to CIBMTR with available CD4 counts at days 100 (D100) and 180 (D180). Patients (median age 51, range 2-75) were categorized into four groups based on GVHD prophylaxis: ex-vivo T cell depletion (TCD/CD34), post-transplant cyclophosphamide (PTCy), calcineurin-inhibitor alone (CNI) or with anti-thymocyte globulin (CNI+ATG). Based upon survival we could identify optimal cut-points for CD4+ T cells in pediatric (age <20y) patients: 248 x 106/L and 420 x 106/L at D100 and D180, respectively; and in adult (age >20y) patients: 104 x 106/L and 115 x 106/L at D100 and D180, respectively. In adults, D100 CD4 count was associated with overall survival, progression-free survival (PFS) and TRM, but not relapse, incidence of infections, or chronic GVHD. Similarly, CD4 counts above the cut-point at D180 in adults were associated with improved OS, PFS, and TRM but no other outcomes. No clinical associations for CD4 counts were identifiable in pediatric patients. These findings underscore the importance of tailoring transplant strategies for adults to optimize immune recovery and improve patient outcomes.},
}

@article {pmid40196517,
year = {2025},
author = {Readshaw, JJ and Doyle, LA and Puiu, M and Kelly, A and Nelson, A and Kaiser, AJ and McGuire, S and Peralta-Acosta, J and Smith, DL and Stoddard, BL and Kaiser, BK and Blower, TR},
title = {PglZ from Type I BREX phage defence systems is a metal-dependent nuclease that forms a sub-complex with BrxB.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40196517},
issn = {2692-8205},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; R01 GM105691/GM/NIGMS NIH HHS/United States ; R01 GM129325/GM/NIGMS NIH HHS/United States ; R15 GM140375/GM/NIGMS NIH HHS/United States ; },
abstract = {BREX (Bacteriophage Exclusion) systems, identified through shared identity with Pgl (Phage Growth Limitation) systems, are a widespread, highly diverse group of phage defence systems found throughout bacteria and archaea. The varied BREX Types harbour multiple protein subunits (between four and eight) and all encode a conserved putative phosphatase (PglZ aka BrxZ) and an equally conserved, putative ATPase (BrxC). Almost all BREX systems also contain a site-specific methyltransferase (PglX aka BrxX). Despite having determined the structure and fundamental biophysical and biochemical behaviours for the PglX methyltransferase, the BrxL effector, the BrxA DNA-binding protein and the BrxR transcriptional regulator, the mechanism by which BREX impedes phage replication remains largely undetermined. In this study, we identify a stable BREX sub-complex of PglZ:BrxB, validate the structure and dynamic behaviour of that sub-complex, and assess the biochemical activity of PglZ, revealing it to be a metal-dependent nuclease. PglZ can cleave cyclic oligonucleotides, linear oligonucleotides, plasmid DNA and both non-modified and modified linear phage genomes. PglZ nuclease activity has no obvious role in BREX-dependent methylation, but does contribute to BREX phage defence. BrxB binding does not impact PglZ nuclease activity. These data contribute to our growing understanding of the BREX phage defence mechanism.},
}

@article {pmid40195998,
year = {2025},
author = {Kareithi, T and D Roche, S and Omollo, V and Ong'wen, PA and Kiptinness, C and Otieno, P and Juma, L and Malen, RC and Harkey, K and Anyona, MO and Curran, K and Banerjee, P and Gichuru, E and Asewe, M and Yu, K and Pintye, J and Mugambi, M and Shah, PD and Sharma, M and Meisner, A and Were, D and Ngure, K and Bukusi, EA and Ortblad, KF},
title = {Testing different models of pharmacy-based HIV pre- and post-exposure prophylaxis initiation and management in Kenya: protocol for a cluster-randomized controlled trial.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {40195998},
issn = {2693-5015},
support = {R00 MH121166/MH/NIMH NIH HHS/United States ; },
abstract = {BACKGROUND: In Kenya, as in many African countries, private pharmacies are ubiquitous, frequently accessed, and underutilized for the delivery of HIV prevention services. Whether enabling private pharmacies to initiate and manage clients on HIV pre- and post-exposure prophylaxis (PrEP and PEP) leads to greater uptake and continuation than the current standard-pharmacy referral to clinic-based PrEP/PEP-is unknown. To address this gap and inform how private pharmacies might partner with the public sector, we are testing several models of pharmacy-delivered PrEP/PEP in comparison to the current standard.

METHODS: The Pharm PrEP cRCT is a 60-pharmacy, four-arm cluster-randomized controlled trial ongoing in Central and Western Kenya (first enrollment: 26 June 2023). Eligible pharmacies were licensed by the government, had a private room, and were willing to complete research activities (including a three-day provider training). Study pharmacies were randomized 1:1:1:1 to: 1) client-sustained delivery, in which clients pay pharmacies 250 KES (~$2 USD) per PrEP/PEP visit, 2) implementor-sustained delivery, in which clients pay nothing and implementors pay pharmacies 250 KES per PrEP/PEP visit, 3) implementor-sustained + counselor-supported delivery, in which clients pay nothing, delivery is supported by an HIV testing services (HTS) counselor, and implementors pay pharmacies 100 KES (~$1 USD) per PrEP/PEP visit, or 4) referral (control), in which clients pay nothing and implementors pay pharmacies 100 KES per referral to clinic-based PrEP/PEP. Pharmacies delivering PrEP/PEP receive supporting commodities free from government stock. Primary outcomes are PrEP initiation and continuation (any refilling) reported by clients 60 days post-enrollment; secondary outcomes include PEP initiation, PEP-to-PrEP transition, repeat PEP use, PrEP/PEP initiation, and PrEP/PEP continuation at 60 and 270 days post-enrollment. Primary analyses will compare each intervention arm to the control; secondary analyses will compare intervention arms to one another. We will additionally assess implementation outcomes (e.g., acceptability, feasibility, cost) from client and provider perspectives.

DISCUSSION: This trial will generate evidence on the potential benefits of leveraging private pharmacies for delivery of PrEP and PEP and the relative effectiveness of pharmacy delivery when subsidized by clients, implementors, and/or supported by HTS counselors. The findings may inform enabling policy and approaches for scale-up.

TRIAL REGISTRATION: ClinicalTrials.gov: NCT05842122.},
}

@article {pmid40195984,
year = {2025},
author = {Fredericks, MN and Kolodner, Z and Waalkes, A and Sawatzki, K and Hao, L and Long, DR and Penewit, K and Midkiff, CC and McCormick, CJ and Beraki, S and Edlefsen, PT and Barrow, J and Greninger, AL and Gale, M and Blair, RV and Salipante, SJ and Fuller, DH and O'Connor, MA},
title = {SIV/SARS-CoV-2 co-infection in rhesus macaques impacts viral shedding, host immunity, the microbiome, and viral evolution.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {40195984},
issn = {2693-5015},
support = {K01 MH123258/MH/NIMH NIH HHS/United States ; P51 OD011104/OD/NIH HHS/United States ; S10 OD030347/OD/NIH HHS/United States ; },
abstract = {People living with HIV (PLWH) have an increased risk of severe COVID-19, including prolonged viral shedding and emergence of mutations. To investigate the simian immunodeficiency virus (SIV) macaque model for HIV/SARS-CoV-2 co-infection, seven SIV+ rhesus macaques were co-infected with SARS-CoV-2. COVID-19 in all macaques was mild. SARS-CoV-2 replication persisted in the upper, but not the lower respiratory tract for 14 days post-infection. Animals showed impaired generation of anti-SARS-CoV-2 antibodies and T-cells. Animals also displayed transient changes in microbial communities in the upper airway and gastrointestinal tract. Evidence of SARS-CoV-2 evolution was observed in the upper respiratory tract. This study demonstrates that SIV/SARS-CoV-2 co-infection in rhesus macaques recapitulates aspects of COVID-19 in PLWH. We show that SIV impairs anti-SARS-CoV-2 immunity, potentially leading to prolonged viral shedding, altered pathogenesis, and viral evolution. This highlights the importance of HIV status in COVID-19 and supports the use of this model for HIV/SARS-CoV-2 co-infection.},
}

@article {pmid40166161,
year = {2025},
author = {Wang, K and Saniei, S and Poddar, N and Autar, S and Carcamo, S and Sreenath, M and Peplinski, JH and Ries, RE and Martinez, IG and Chao, C and Mei, AH and Rahman, N and Mekerishvili, L and Quijada-Álamo, M and Freed, G and Zhang, M and Lachman, K and Diaz, Z and Gonzalez, MM and Zhang, J and Pham, G and Filipescu, D and Berisa, M and Balestra, T and Reisz, JA and D'Alessandro, A and Puleston, DJ and Bernstein, E and Chipuk, JE and Wunderlich, M and Tasian, SK and Marcellino, BK and Glass, IA and , and Sturgeon, CM and Landau, DA and Chen, Z and Papapetrou, EP and Izzo, F and Meshinchi, S and Hasson, D and Wagenblast, E},
title = {Ontogeny Dictates Oncogenic Potential, Lineage Hierarchy, and Therapy Response in Pediatric Leukemia.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40166161},
issn = {2692-8205},
support = {S10 OD026880/OD/NIH HHS/United States ; R01 CA290681/CA/NCI NIH HHS/United States ; R01 CA292503/CA/NCI NIH HHS/United States ; UL1 TR004419/TR/NCATS NIH HHS/United States ; R24 HD000836/HD/NICHD NIH HHS/United States ; S10 OD030463/OD/NIH HHS/United States ; P30 CA196521/CA/NCI NIH HHS/United States ; },
abstract = {Accumulating evidence links pediatric cancers to prenatal transformation events, yet the influence of the developmental stage on oncogenesis remains elusive. We investigated how hematopoietic stem cell developmental stages affect leukemic transformation, disease progression, and therapy response using a novel, humanized model of NUP98∷NSD1-driven pediatric acute myeloid leukemia, that is particularly aggressive with WT1 co-mutations. Fetal-derived hematopoietic stem cells readily transform into leukemia, and WT1 mutations further enhance stemness and alter lineage hierarchy. In contrast, stem cells from later developmental stages become progressively resistant to transformation. Single-cell analyses revealed that fetal-origin leukemia stem cells exhibit greater quiescence and reliance on oxidative phosphorylation than their postnatal counterparts. These differences drive distinct therapeutic responses, despite identical oncogenic mutations. In patients, onco-fetal transcriptional programs correlate with worse outcomes. By targeting key vulnerabilities of fetal-origin leukemia cells, we identified combination therapies that significantly reduce aggressiveness, highlighting the critical role of ontogeny in pediatric cancer treatment.},
}

@article {pmid40166020,
year = {2025},
author = {Peluso, MJ and Sandel, DA and Deitchman, AN and Kim, SJ and Dalhuisen, T and Tummala, HP and Tibúrcio, R and Zemelko, L and Borgo, GM and Singh, SS and Schwartz, K and Deswal, M and Williams, MC and Hoh, R and Shimoda, M and Narpala, S and Serebryannyy, L and Khalili, M and Vendrame, E and SenGupta, D and Whitmore, LS and Tisoncik-Go, J and Gale, M and Koup, RA and Mullins, JI and Felber, BK and Pavlakis, GN and Reeves, JD and Petropoulos, CJ and Glidden, DV and Spitzer, MH and Gama, L and Caskey, M and Nussenzweig, MC and Chew, KW and Henrich, TJ and Yukl, SA and Cohn, LB and Deeks, SG and Rutishauser, RL},
title = {Combination immunotherapy induces post-intervention control of HIV.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {40166020},
issn = {2693-5015},
support = {R01 DE032033/DE/NIDCR NIH HHS/United States ; K23 AI162249/AI/NIAID NIH HHS/United States ; UM1 AI164560/AI/NIAID NIH HHS/United States ; P30 AI027763/AI/NIAID NIH HHS/United States ; R01 AI170239/AI/NIAID NIH HHS/United States ; P30 AI152501/AI/NIAID NIH HHS/United States ; P01 AI169606/AI/NIAID NIH HHS/United States ; T32 GM136547/GM/NIGMS NIH HHS/United States ; K23 AI157875/AI/NIAID NIH HHS/United States ; K24 AA022523/AA/NIAAA NIH HHS/United States ; UL1 TR001872/TR/NCATS NIH HHS/United States ; T32 AI060530/AI/NIAID NIH HHS/United States ; P01 AI178375/AI/NIAID NIH HHS/United States ; },
abstract = {The identification of therapeutic strategies to induce sustained antiretroviral therapy (ART)-free control of HIV infection is a major priority.[1] Combination immunotherapy including HIV vaccination, immune stimulation/latency reversal, and passive transfer of broadly neutralizing antibodies (bNAbs) has shown promise in non-human primate models,[2-7] but few studies have translated such approaches into people. Here, we performed a single-arm, proof-of-concept combination study of these three approaches in ten people with HIV on ART that included (1) therapeutic vaccination with an HIV/Gag conserved element (CE)-targeted DNA+IL-12 prime/MVA boost regimen followed by (2) administration of two bNAbs (10-1074 and VRC07-523LS) and a toll-like receptor 9 (TLR9) agonist (lefitolimod) during ART suppression, followed by (3) repeat bNAb administration at the time of ART interruption. Seven of the ten participants exhibited partial (low viral load set point) or complete (aviremic) post-intervention control after stopping ART, independent of residual bNAb plasma levels. Robust expansion of activated CD8+ T cells early in response to rebounding virus correlated with lower viral load set points. These data suggest that combination immunotherapy approaches might prove effective to induce sustained control of HIV by slowing rebound and improving CD8+ T cell responses, and that these approaches should continue to be optimized.},
}

@article {pmid40161829,
year = {2025},
author = {Agrawal, P and Khechaduri, A and Salladay, KR and MacCamy, A and Ralph, DK and Riker, A and Stuart, AB and Siddaramaiah, LK and Shen, X and Matsen, FA and Montefiori, D and Stamatatos, L},
title = {Increased immunogen valency improves the maturation of vaccine-elicited HIV-1 VRC01-class antibodies.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40161829},
issn = {2692-8205},
support = {P01 AI138212/AI/NIAID NIH HHS/United States ; R01 AI143370/AI/NIAID NIH HHS/United States ; R01 AI146028/AI/NIAID NIH HHS/United States ; R01 AI177095/AI/NIAID NIH HHS/United States ; },
abstract = {Antibodies belonging to the VRC01-class display broad and potent neutralizing activities and have been isolated from several people living with HIV (PLWH). A member of that class, monoclonal antibody VRC01, was shown to reduce HIV-acquisition in two phase 2b efficacy trials. VRC01-class antibodies are therefore expected to be a key component of an effective HIV-1 vaccine. In contrast to the VRC01-class antibodies that are highly mutated, their unmutated forms do not engage HIV-1 envelope (Env) and do not display neutralizing activities. Hence, specifically modified Env-derived proteins have been designed to engage the unmutated forms of VRC01-class antibodies, and to activate the corresponding naïve B cells. Selected heterologous Env must then be used as boost immunogens to guide the proper maturation of these elicited VRC01-class antibodies. Here we examined whether and how the valency of the prime and boost immunogens influences VRC01-class antibody-maturation. Our findings indicate that, indeed the valency of the immunogen affects the maturation of elicited antibody responses by preferentially selecting VRC01-class antibodies that have accumulated somatic mutations present in broadly neutralizing VRC01-class antibodies isolated from PLWH. As a result, antibodies isolated from animals immunized with the higher valency immunogens display broader Env cross-binding properties and improved neutralizing potentials than those isolated from animals immunized with the lower valency immunogens. Our results are relevant to current and upcoming phase 1 clinical trials that evaluate the ability of novel immunogens aiming to elicit cross-reactive VRC01-class antibody responses.},
}

@article {pmid40161760,
year = {2025},
author = {Simonich, CAL and McMahon, TE and Ju, X and Yu, TC and Brunette, N and Stevens-Ayers, T and Boeckh, MJ and King, NP and Greninger, AL and Bloom, JD},
title = {RSV F evolution escapes some monoclonal antibodies but does not strongly erode neutralization by human polyclonal sera.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40161760},
issn = {2692-8205},
support = {K12 HD000850/HD/NICHD NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; R01 AI141707/AI/NIAID NIH HHS/United States ; U19 AI181767/AI/NIAID NIH HHS/United States ; },
abstract = {Vaccines and monoclonal antibodies targeting the respiratory syncytial virus (RSV) fusion protein (F) have recently begun to be widely used to protect infants and high-risk adults. Some other viral proteins evolve to erode polyclonal antibody neutralization and escape individual monoclonal antibodies. However, little is known about how RSV F evolution affects antibodies. Here we develop an experimental system for measuring neutralization titers against RSV F using pseudotyped lentiviral particles. This system is easily adaptable to evaluate neutralization of relevant clinical strains. We apply this system to demonstrate that natural evolution of RSV F leads to escape from some monoclonal antibodies, but at most modestly affects neutralization by polyclonal serum antibodies. Overall, our work sheds light on RSV antigenic evolution and describes a tool to measure the ability of antibodies and sera to neutralize contemporary RSV strains.},
}

@article {pmid40249804,
year = {2025},
author = {Bhattacharya, T and Alleman, EM and Freeman, TS and Noyola, AC and Emerman, M and Malik, HS},
title = {A conserved opal termination codon optimizes a temperature-dependent trade-off between protein production and processing in alphaviruses.},
journal = {Science advances},
volume = {11},
number = {16},
pages = {eads7933},
doi = {10.1126/sciadv.ads7933},
pmid = {40249804},
issn = {2375-2548},
mesh = {*Codon, Terminator/genetics ; Animals ; *Temperature ; *Alphavirus/genetics ; *Protein Biosynthesis ; Virus Replication/genetics ; *Sindbis Virus/genetics ; *Viral Proteins/genetics/metabolism ; Humans ; RNA, Viral/genetics ; Mutation ; Cell Line ; },
abstract = {Most mosquito-transmitted alphaviruses encode a premature opal termination codon upstream of their viral polymerase. We show that the Sindbis virus (SINV) opal codon outperforms other stop codons in primate cells at 37°C due to optimal translational readthrough. However, increased readthrough of all stop codons reduces opal preference at 28°C in primate and mosquito cells. Opal also outperforms all sense codons because opal-to-sense substitutions lead to excess polyprotein production at 37°C, disrupting orderly polyprotein processing and production of viral genomic RNAs (gRNAs) required for virus production. Increased readthrough at 28°C dampens the fitness advantages of opal codons. Unexpectedly, we find that a naturally occurring SINV mutation restores sense-codon fitness by further delaying polyprotein processing, allowing adequate time to produce gRNAs. Similar temperature-dependent mechanisms occur in the distantly related dual-host alphavirus, Ross River virus. Our work highlights sophisticated strategies dual-host alphaviruses use to optimize replication in divergent temperatures through a single codon.},
}

*Codon, Terminator/genetics
Animals
*Temperature
*Alphavirus/genetics
*Protein Biosynthesis
Virus Replication/genetics
*Sindbis Virus/genetics
*Viral Proteins/genetics/metabolism
Humans
RNA, Viral/genetics
Mutation
Cell Line

@article {pmid40249111,
year = {2025},
author = {Sievers, P and Arora, S and Hielscher, T and Savran, D and Schrimpf, D and Banan, R and Vonhören, D and Pusch, S and Sill, M and Appay, R and Wirsching, HG and Hortobagyi, T and Dohmen, H and Acker, T and Kohlhof-Meinecke, P and Schweizer, L and Wefers, AK and Harter, PN and Hartmann, C and Beschorner, R and Schittenhelm, J and Behling, F and Tabatabai, G and Mawrin, C and Snuderl, M and Maas, SLN and Wesseling, P and Brandner, S and Korshunov, A and Ratliff, M and Krieg, SM and Wick, W and Jones, DTW and Pfister, SM and Holland, EC and von Deimling, A and Szulzewsky, F and Sahm, F},
title = {Molecular signatures define BAP1-altered meningioma as a distinct CNS tumor with deregulation of Polycomb repressive complex target genes.},
journal = {Neuro-oncology},
volume = {},
number = {},
pages = {},
doi = {10.1093/neuonc/noaf105},
pmid = {40249111},
issn = {1523-5866},
abstract = {BACKGROUND: Meningiomas are the most common primary intracranial neoplasms, with highly variable patient outcomes. While most meningiomas are benign, a significant subset recurs postoperatively, presenting substantial treatment challenges. BAP1 gene inactivation has been suggested as a marker for aggressive meningiomas, although its precise molecular and clinical roles remain poorly understood.

METHODS: To comprehensively investigate BAP1-altered meningiomas, we used six meningiomas with known BAP1 alterations as a discovery set. Genome-wide DNA methylation profiling of these samples, along 11,151 reference meningiomas, identified a distinct molecular cluster (n = 42) using unsupervised visualization approaches. These tumors were further characterized by DNA/RNA sequencing, histopathological examination, and a retrospective review of clinical data, compared to reference meningioma cohorts, providing a thorough characterization of this rare tumor subtype.

RESULTS: Our integrative analysis revealed BAP1-altered meningiomas as a distinct CNS tumor subtype, characterized by recurrent loss of chromosome 3p21 and driven by various BAP1-inactivating alterations. Although rhabdoid morphology is present in some cases, it is not exclusive and should not be used as a grading criterion. Progression-free survival analysis showed a median of 21 months (95% CI: 12-NA), with a 2-year overall survival rate of 79% (95% CI: 60%-100%), highlighting the aggressive nature of these tumors. Gene expression profiling revealed upregulation of PRC target genes, dysregulated Polycomb signaling, and elevated expression in several cellular and growth factor pathways.

CONCLUSIONS: BAP1-altered meningiomas represent a distinct and aggressive CNS tumor subtype associated with PRC dysregulation and recurrent 3p chromosome loss. These findings support the designation "meningioma, BAP1-altered."},
}

@article {pmid40248714,
year = {2025},
author = {Girard, B and Figueroa, AL and De Rosa, SC and McElrath, MJ and Azzi, JR and Stolman, D and Siangphoe, U and de Windt, E and Miller, JM and Das, R and Priddy, F},
title = {mRNA-1273 COVID-19 vaccine induces CD4+ T-cell responses among solid organ transplant recipients.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1505871},
pmid = {40248714},
issn = {1664-3224},
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; 2019-nCoV Vaccine mRNA-1273/immunology ; *CD4-Positive T-Lymphocytes/immunology ; *COVID-19/prevention & control/immunology ; *COVID-19 Vaccines/immunology/administration & dosage ; Cytokines ; Immunity, Cellular ; Kidney Transplantation ; *Organ Transplantation ; *SARS-CoV-2/immunology ; Spike Glycoprotein, Coronavirus/immunology ; Transplant Recipients ; },
abstract = {BACKGROUND: Cell-mediated immunity may provide durable protection against severe COVID-19, including among solid organ transplant recipients (SOTRs). This exploratory analysis in the open-label phase 3b trial evaluated cell-mediated immunity of mRNA-1273 in a subset of participants (59 kidney and 33 liver SOTRs; 12 immunocompetent participants).

METHODS: In Part A, SOTRs received three 100-µg doses of mRNA-1273; immunocompetent participants received two doses. In Part B, an additional 100-µg dose was offered ≥4 months after the primary series. SARS-CoV-2 spike (S) protein-specific T-cell responses were measured by intracellular cytokine staining and polyfunctionality analyses.

RESULTS: The primary series and additional dose of mRNA-1273 induced S protein-specific CD4[+] T-cell responses exhibiting a Th-1-biased profile in both SOTRs and immunocompetent participants; however, response rates and magnitudes were lower among SOTRs. S protein-specific Th-2 CD4[+] T-cell responses were below those observed for Th-1; CD8[+] T-cell responses were not as robust among SOTRs compared with immunocompetent participants. Kidney SOTRs received multiple immunosuppressants and had lower cell-mediated immunity responses than liver SOTRs. Polyfunctional responses exhibited Th-1 cytokine signatures with ≤5 functional markers reported in SOTRs and immunocompetent participants.

CONCLUSION: Overall, a three-dose mRNA-1273 primary series elicited Th-1-biased CD4[+] T-cell responses among SOTRs that were improved with an additional dose.

CLINICAL TRIAL REGISTRATION: https://beta.clinicaltrials.gov/study/NCT04860297?term=NCT04860297%20&rank=1, identifier NCT04860297.},
}

Adult
Aged
Female
Humans
Male
Middle Aged
2019-nCoV Vaccine mRNA-1273/immunology
*CD4-Positive T-Lymphocytes/immunology
*COVID-19/prevention & control/immunology
*COVID-19 Vaccines/immunology/administration & dosage
Cytokines
Immunity, Cellular
Kidney Transplantation
*Organ Transplantation
*SARS-CoV-2/immunology
Spike Glycoprotein, Coronavirus/immunology
Transplant Recipients

@article {pmid40246795,
year = {2025},
author = {Szabados, BE and Guerrero-Ramos, F and Grande, E and Grivas, P and Grünwald, V and Miguel, MC and Hussain, SA and Kulkarni, GS and Wilson, AL and Shore, ND and Sridhar, SS and Hoyt, M and Strumeier, S and Sutton, J and Brinkmann, J and Teresi, RE and Todenhöfer, T},
title = {On the Horizon: A Global Multidisciplinary Perspective on Delivering Emerging Therapies for Patients with BCG-Naïve High-Risk NMIBC.},
journal = {Oncology and therapy},
volume = {},
number = {},
pages = {},
pmid = {40246795},
issn = {2366-1089},
abstract = {Patients with high-risk non-muscle invasive bladder cancer (NMIBC) are generally treated with transurethral resection of the bladder tumor followed by intravesical bacillus Calmette-Guérin (BCG), the current standard of care. However, recurrence or progression is common and may result in patients requiring radical cystectomy. Additionally, BCG continues to be in short supply worldwide. Therefore, there is an unmet need for new therapies that provide durable disease control and maintain quality of life. In the BCG-naïve high-risk NMIBC setting, potential new treatment options are emerging, with several regimens combining intravesical therapy with systemic PD-1 or PD-L1-directed immune checkpoint inhibitors (ICIs) currently under investigation in several Phase 3 trials. In routine clinical practice, NMIBC has traditionally been managed almost entirely by urologists. However, the introduction of systemic ICIs would likely require medical oncology expertise to help assess patients' fitness for these therapies and potentially for treatment administration and immune-related adverse event management. While multidisciplinary workflows are common practice for advanced bladder cancer, they would represent a paradigm shift in NMIBC. Based on current experience of managing patients with NMIBC across different countries and healthcare systems from our perspective as urologists, medical oncologists, and nurses, we discuss best practices for the potential integration of emerging therapies such as ICIs into the treatment of BCG-naïve high-risk NMIBC. We emphasize the need for multidisciplinary care, either through formalized multidisciplinary teams or cross-discipline collaborative workflows adapted to local needs, to ensure efficient coordination and sharing of responsibilities. Specialized nurses have the potential to play key roles across multiple aspects of patient care. We also highlight the crucial importance of effective communication across teams, increases in resourcing, and education for healthcare professionals, patients, and caregivers to enable eligible patients with high-risk NMIBC to benefit optimally from the introduction of these potential new treatment options.},
}

@article {pmid40245370,
year = {2025},
author = {Triplette, M},
title = {Do Differences in Comorbidity Explain Sex-based Differences in Lung Cancer Screening Outcomes?.},
journal = {Annals of the American Thoracic Society},
volume = {},
number = {},
pages = {},
doi = {10.1513/AnnalsATS.202504-391ED},
pmid = {40245370},
issn = {2325-6621},
}

@article {pmid40245079,
year = {2025},
author = {Trouth, A and Ravichandran, K and Gafken, PR and Martire, S and Boyle, GE and Veronezi, GMB and La, V and Namciu, SJ and Banaszynski, LA and Sarthy, JF and Ramachandran, S},
title = {The length of G1 phase is an essential determinant of H3K27me3 landscape across diverse cell types.},
journal = {PLoS biology},
volume = {23},
number = {4},
pages = {e3003119},
doi = {10.1371/journal.pbio.3003119},
pmid = {40245079},
issn = {1545-7885},
abstract = {Stem cells have lower facultative heterochromatin as defined by trimethylation of histone H3 lysine 27 (H3K27me3) compared to differentiated cells. However, the mechanisms underlying these differential H3K27me3 levels remain elusive. Because H3K27me3 levels are diluted 2-fold in every round of replication and then restored through the rest of the cell cycle, we reasoned that the cell cycle length could be a key regulator of total H3K27me3 levels. Here, we propose that a short G1 phase restricts H3K27me3 levels in stem cells. To test this model, we determined changes to H3K27me3 levels in mouse embryonic stem cells (mESCs) globally and at specific loci upon G1 phase lengthening - accomplished by thymidine block or growth in the absence of serum (with the "2i medium"). H3K27me3 levels in mESCs increase with G1 arrest when grown in serum and in 2i medium. Additionally, we observed via CUT&RUN and ChIP-seq that regions that gain H3K27me3 in G1 arrest and 2i media overlap, supporting our model of G1 length as a critical regulator of the stem cell epigenome. Furthermore, we demonstrate the inverse effect - that G1 shortening in differentiated human HEK293 cells results in a loss of H3K27me3 levels. Finally, in human tumor cells with extreme H3K27me3 loss, lengthening of the G1 phase leads to H3K27me3 recovery despite the presence of the dominant negative, sub-stoichiometric H3.K27M mutation. Our results indicate that G1 length is an essential determinant of H3K27me3 landscapes across diverse cell types.},
}

@article {pmid40243688,
year = {2025},
author = {Yap, TA and Goldman, JW and Vinayak, S and Tomova, A and Hamilton, E and Naito, Y and Giordano, A and Bondarenko, I and Yamashita, T and Zhou, L and Moreau, A and Neumann, H and Tougias, J and Liu, F and Park, J and Delioukina, M and Jhaveri, K},
title = {First-In-Human Phase 1/2a Study of the First-In-Class CDK2/4/6 Inhibitor PF-06873600 Alone or with Endocrine Therapy in Patients with Breast Cancer.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {},
number = {},
pages = {},
doi = {10.1158/1078-0432.CCR-24-2740},
pmid = {40243688},
issn = {1557-3265},
abstract = {PURPOSE: The discovery that cyclin E overexpression is a key CDK4/6 inhibitor resistance mechanism has reinvigorated interest in targeting CDK2, and simultaneous inhibition of CDK2/4/6 as a novel therapeutic approach. This first-in-human study assessed safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of PF-06873600, the first-in-class inhibitor of CDK2/4/6.

PATIENTS AND METHODS: Dose escalation included 78 patients with advanced breast cancer, triple negative breast cancer, or ovarian cancer who received oral PF-06873600 1-50 mg twice daily (BID) (Part 1A, n=51), or PF-06873600 with endocrine therapy (Part 1B, n=16; Part 1C n=11) to determine the recommended dose for expansion (RDE). Dose expansion (Part 2A, n=45; Part 2C, n=28) assessed preliminary antitumor activity, safety and tolerability at the RDE in combination with fulvestrant in patients with HR+/HER2- mBC. Pharmacodynamics and translational readouts were assessed by phosphorylated Rb and Ki67 in tumor biopsies and circulating tumor DNA (ctDNA).

RESULTS: The RDE of PF-06873600 was 25mg BID. During dose escalation, six of 42 (14.3%) evaluable patients had treatment-related dose-limiting toxicities. Most common all-causality adverse events (N=151) were nausea (62.9%), anemia (44.4%) and fatigue (43.7%). Reductions in Ki67-positive cells, pRb H-score, and ctDNA levels were observed. Three RECIST partial responses (PRs) were observed in Part 1. In Part 2A there were three PRs (objective response rate [ORR] 6.7%, 95% CI: 1.4-18.3%) and, in Part 2C, five PRs (ORR 22.7%, 95% CI: 7.8-45.4%).

CONCLUSIONS: PF-06873600 demonstrated a benefit-risk profile consistent with the CDK4/6 inhibitor class of drugs, with preliminary clinical activity in HR+/HER2- mBC.

CLINICALTRIALS: gov identifier: NCT03519178.},
}

@article {pmid40243533,
year = {2025},
author = {Thomas, CE and Takashima, Y and Buchanan, DD and Wesselink, E and Qu, C and Hsu, L and Dias Costa, A and Gallinger, S and Grant, RC and Huyghe, JR and Thomas, S and Ugai, S and Zhong, Y and Matsuda, K and Ugai, T and Peters, U and Ogino, S and Nowak, JA and Phipps, AI},
title = {Density of T cell subsets in colorectal cancer in relation to disease-specific survival.},
journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1158/1055-9965.EPI-25-0287},
pmid = {40243533},
issn = {1538-7755},
abstract = {BACKGROUND: Prior studies have demonstrated that the overall density of T cells in colorectal tumors is favorably associated with colorectal cancer (CRC) survival; however, few studies have considered the potentially distinct roles of heterogeneous T cell subsets in different tissue regions in relation to CRC outcomes.

METHODS: Including 1,113 CRC tumors from three observational studies, we conducted in-situ T cell profiling using a customized 9-plex [CD3, CD4, CD8, CD45RA, CD45RO, FOXP3, KRT (keratin), MKI67 (Ki-67), and DAPI] multispectral immunofluorescence assay. Multivariable-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of T cell subset densities in both epithelial and stromal tissue areas in CRC with disease-specific survival.

RESULTS: Higher CD3+CD4+ and CD3+CD8+ naive, memory, and regulatory T cell densities were significantly associated with better CRC-specific survival in both epithelial and stromal tissue areas (HRs highest quantile versus lowest quantile ranging 0.41-0.68). These associations persisted in models further adjusted for stage at diagnosis and were largely consistent when stratified by microsatellite instability (MSI) status. However, the further stratification into CD4+ or CD8+ T cell subsets beyond CD3+ subsets did not significantly improve how well our model explains CRC prognosis.

CONCLUSIONS: The density of T cells in CRC tissue, both overall and for several T cell subset populations, is significantly associated with CRC-specific survival independent of MSI status and stage at diagnosis.

IMPACT: Higher levels of T cell densities in different locations with different functions are associated with better CRC-specific survival.},
}

@article {pmid40241769,
year = {2025},
author = {Pang, Y and Li, Q and Sergi, Z and Yu, G and Kim, O and Lu, P and Chan, M and Sang, X and Wang, H and Ranjan, A and Robey, RW and Soheilian, F and Tran, B and Núñez, FJ and Zhang, M and Song, H and Zhang, W and Davis, D and Gilbert, MR and Gottesman, MM and Liu, Z and Thomas, CJ and Castro, MG and Gujral, TS and Wu, J},
title = {Exploiting the therapeutic vulnerability of IDH-mutant gliomas with zotiraciclib.},
journal = {iScience},
volume = {28},
number = {4},
pages = {112283},
pmid = {40241769},
issn = {2589-0042},
abstract = {Isocitrate dehydrogenase (IDH)-mutant gliomas have distinctive metabolic and biological traits that potentially render them susceptible to targeted treatments. Here, by conducting a high-throughput drug screen, we pinpointed a specific vulnerability of IDH-mutant gliomas to zotiraciclib (ZTR). ZTR exhibited selective growth inhibition across multiple IDH-mutant glioma in vitro and in vivo models. Mechanistically, ZTR at low doses suppressed CDK9 and RNA Pol II phosphorylation in IDH-mutant cells, disrupting mitochondrial function and NAD+ production, resulting in oxidative stress. Integrated biochemical profiling of ZTR kinase targets and transcriptomics unveiled that ZTR-induced bioenergetic failure was linked to the suppression of PIM kinase activity. We posit that the combination of mitochondrial dysfunction and an inability to adapt to oxidative stress resulted in significant cell death upon ZTR treatment, ultimately increasing the therapeutic vulnerability of IDH-mutant gliomas. These findings prompted a clinical trial evaluating ZTR in IDH-mutant gliomas (NCT05588141).},
}

@article {pmid40240612,
year = {2025},
author = {Nesselbush, MC and Luca, BA and Jeon, YJ and Jabara, I and Meador, CB and Garofalo, A and Binkley, MS and Hui, AB and van 't Erve, I and Xu, N and Shi, WY and Liu, KJ and Sugio, T and Kastelowitz, N and Hamilton, EG and Liu, CL and Olsen, M and Bonilla, RF and Wang, YP and Jiang, A and Lau, B and Eichholz, J and Banwait, M and Schroers-Martin, J and Boegeholz, J and King, DA and Luikart, H and Esfahani, MS and Mehrmohamadi, M and Stehr, H and Raclin, T and Tibshirani, R and Khush, K and Srinivas, S and Yu, H and Rogers, AJ and Nair, VS and Isbell, JM and Li, BT and Piotrowska, Z and Sequist, LV and Hata, AN and Neal, JW and Wakelee, HA and Gentles, AJ and Alizadeh, AA and Diehn, M},
title = {An ultrasensitive method for detection of cell-free RNA.},
journal = {Nature},
volume = {},
number = {},
pages = {},
pmid = {40240612},
issn = {1476-4687},
abstract = {Sensitive methods for detection of cell-free RNA (cfRNA) could facilitate non-invasive gene expression profiling and monitoring of diseases[1-6]. Here we describe RARE-seq (random priming and affinity capture of cfRNA fragments for enrichment analysis by sequencing), a method optimized for cfRNA analysis. We demonstrate that platelet contamination can substantially confound cfRNA analyses and develop an approach to overcome it. In analytical validations, we find RARE-seq to be approximately 50-fold more sensitive for detecting tumour-derived cfRNA than whole-transcriptome RNA sequencing (RNA-seq), with a limit of detection of 0.05%. To explore clinical utility, we profiled 437 plasma samples from 369 individuals with cancer or non-malignant conditions and controls. Detection of non-small-cell lung cancer expression signatures in cfRNA increased with stage (6 out of 20 (30%) in stage I; 5 out of 8 (63%) in stage II; 10 out of 15 (67%) in stage III; 80 out of 96 (83% sensitivity) in stage IV at 95% specificity) and RARE-seq was more sensitive than tumour-naive circulating tumour DNA (ctDNA) analysis. In patients with EGFR-mutant non-small-cell lung cancer who developed resistance to tyrosine kinase inhibitors, we detected both histological transformation and mutation-based resistance mechanisms. Finally, we demonstrate the potential utility of RARE-seq for determination of tissue of origin, assessing benign pulmonary conditions and tracking response to mRNA vaccines. These results highlight the potential value of ultrasensitive cfRNA analysis and provide proof of concept for diverse clinical applications.},
}

@article {pmid40240607,
year = {2025},
author = {Mahendrawada, L and Warfield, L and Donczew, R and Hahn, S},
title = {Low overlap of transcription factor DNA binding and regulatory targets.},
journal = {Nature},
volume = {},
number = {},
pages = {},
pmid = {40240607},
issn = {1476-4687},
abstract = {DNA sequence-specific transcription factors (TFs) modulate transcription and chromatin architecture, acting from regulatory sites in enhancers and promoters of eukaryotic genes[1,2]. How multiple TFs cooperate to regulate individual genes is still unclear. In yeast, most TFs are thought to regulate transcription via binding to upstream activating sequences, which are situated within a few hundred base pairs upstream of the regulated gene[3]. Although this model has been validated for individual TFs and specific genes, it has not been tested in a systematic way. Here we integrated information on the binding and expression targets for the near-complete set of yeast TFs and show that, contrary to expectations, there are few TFs with dedicated activator or repressor roles, and that most TFs have a dual function. Although nearly all protein-coding genes are regulated by one or more TFs, our analysis revealed limited overlap between TF binding and gene regulation. Rapid depletion of many TFs also revealed many regulatory targets that were distant from detectable TF binding sites, suggesting unexpected regulatory mechanisms. Our study provides a comprehensive survey of TF functions and offers insights into interactions between the set of TFs expressed in a single cell type and how they contribute to the complex programme of gene regulation.},
}

@article {pmid40240114,
year = {2025},
author = {Ebadi, M and Tseng, YD},
title = {Old but Gold Radiation.},
journal = {International journal of radiation oncology, biology, physics},
volume = {122},
number = {1},
pages = {7-8},
doi = {10.1016/j.ijrobp.2024.12.042},
pmid = {40240114},
issn = {1879-355X},
}

@article {pmid40241937,
year = {2024},
author = {Wright, C and Meng, Q and Breshock, MR and Atta, L and Taub, MA and Jager, LR and Muschelli, J and Hicks, SC},
title = {Open Case Studies: Statistics and Data Science Education through Real-World Applications.},
journal = {Journal of statistics and data science education : an official journal of the of the American Statistical Association},
volume = {32},
number = {4},
pages = {331-344},
pmid = {40241937},
issn = {2693-9169},
support = {U24 HG010263/HG/NHGRI NIH HHS/United States ; UE5 CA254170/CA/NCI NIH HHS/United States ; UL1 TR003098/TR/NCATS NIH HHS/United States ; },
abstract = {With unprecedented and growing interest in data science education, there are limited educator materials that provide meaningful opportunities for learners to practice statistical thinking, as defined by Wild and Pfannkuch, with messy data addressing real-world challenges. As a solution, Nolan and Speed advocated for bringing applications to the forefront in undergraduate statistics curriculum with the use of in-depth case studies to encourage and develop statistical thinking in the classroom. Limitations to this approach include the significant time investment required to develop a case study - namely, to select a motivating question and to create an illustrative data analysis - and the domain expertise needed. As a result, case studies based on realistic challenges, not toy examples, are scarce. To address this, we developed the Open Case Studies (opencasestudies.org) project, which offers a new statistical and data science education case study model. This educational resource provides self-contained, multimodal, peer-reviewed, and open-source guides (or case studies) from real-world examples for active experiences of complete data analyses. We developed an educator's guide describing how to most effectively use the case studies, how to modify and adapt components of the case studies in the classroom, and how to contribute new case studies (opencasestudies.org/OCS_Guide).},
}

@article {pmid40239994,
year = {2025},
author = {Shen, BW and Heiter, D and Yang, W and Xu, SY and Stoddard, BL},
title = {Cryo-EM structures of DNA-free and DNA-bound BsaXI: architecture of a Type IIB restriction-modification enzyme.},
journal = {Nucleic acids research},
volume = {53},
number = {7},
pages = {},
pmid = {40239994},
issn = {1362-4962},
support = {R01 GM049857/GM/NIGMS NIH HHS/United States ; R35 GM148166/GM/NIGMS NIH HHS/United States ; grid.436923.9//EMSL/ ; U24 GM129547/GM/NIGMS NIH HHS/United States ; U24GM129547/GF/NIH HHS/United States ; },
mesh = {Cryoelectron Microscopy ; *DNA/chemistry/metabolism ; *Deoxyribonucleases, Type II Site-Specific/chemistry/ultrastructure/genetics/metabolism ; Models, Molecular ; DNA Cleavage ; Protein Binding ; Binding Sites ; Protein Conformation ; },
abstract = {We have determined multiple cryogenic electron microscopy (cryo-EM) structures of the Type IIB restriction-modification enzyme BsaXI. Such enzymes cleave DNA on both sides of their recognition sequence and share features of Types I, II, and III restriction systems. BsaXI forms a heterotrimeric (RM)2S assemblage in the presence and absence of bound DNA. Two unique structural motifs-a multi-helical "knob" and a long antiparallel double-helical "paddle"-are involved in DNA binding and cleavage. Binding of the DNA target triggers a large conformational change from an 'open' to 'closed' configuration, resulting in a mixture of two different conformations with respect to the positioning of the S subunit and its target recognition domains on the enzyme's bipartite DNA target site. Structure-guided mutagenesis studies implicated two clusters of residues in the RM subunit as being critical for DNA cleavage, both are located proximal to a DNA cleavage site. One corresponds to a canonical PD-(D/E)xK endonuclease site in the N-terminal endonuclease domain, while the other corresponds to residues clustered within the paddle motif (near to the C-terminal end of the RM subunit). This analysis facilitates a comparison of three potential mechanisms by which such enzymes cleave DNA on each side of the bound target.},
}

Cryoelectron Microscopy
*DNA/chemistry/metabolism
*Deoxyribonucleases, Type II Site-Specific/chemistry/ultrastructure/genetics/metabolism
Models, Molecular
DNA Cleavage
Protein Binding
Binding Sites
Protein Conformation

@article {pmid40239646,
year = {2025},
author = {Zhu, Y and Balaji, A and Han, M and Andronov, L and Roy, AR and Wei, Z and Chen, C and Miles, L and Cai, S and Gu, Z and Tse, A and Yu, BC and Uenaka, T and Lin, X and Spakowitz, AJ and Moerner, WE and Qi, LS},
title = {High-resolution dynamic imaging of chromatin DNA communication using Oligo-LiveFISH.},
journal = {Cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cell.2025.03.032},
pmid = {40239646},
issn = {1097-4172},
abstract = {Three-dimensional (3D) genome dynamics are crucial for cellular functions and disease. However, real-time, live-cell DNA visualization remains challenging, as existing methods are often confined to repetitive regions, suffer from low resolution, or require complex genome engineering. Here, we present Oligo-LiveFISH, a high-resolution, reagent-based platform for dynamically tracking non-repetitive genomic loci in diverse cell types, including primary cells. Oligo-LiveFISH utilizes fluorescent guide RNA (gRNA) oligo pools generated by computational design, in vitro transcription, and chemical labeling, delivered as ribonucleoproteins. Utilizing machine learning, we characterized the impact of gRNA design and chromatin features on imaging efficiency. Multi-color Oligo-LiveFISH achieved 20-nm spatial resolution and 50-ms temporal resolution in 3D, capturing real-time enhancer and promoter dynamics. Our measurements and dynamic modeling revealed two distinct modes of chromatin communication, and active transcription slows enhancer-promoter dynamics at endogenous genes like FOS. Oligo-LiveFISH offers a versatile platform for studying 3D genome dynamics and their links to cellular processes and disease.},
}

@article {pmid40239400,
year = {2025},
author = {Shatila, M and Cruz, CC and Lu, L and Abdul-Baki, K and Baerman, E and Takigawa, K and Rivera, AU and Lee, IJ and Ngo, S and Sperling, G and Aleem, AS and Menon, R and Sullivan, A and Vemulapalli, V and Natha, C and Gupta, T and Khan, A and Mittal, N and Coleman, G and Salim, H and Wali, S and Varatharajalu, K and Kim, KC and Reddy, SA and Grivas, P and Thomas, AS and Wang, Y},
title = {The association between metformin use, immune mediated colitis and overall survival in patients treated with checkpoint inhibitor.},
journal = {European journal of cancer (Oxford, England : 1990)},
volume = {221},
number = {},
pages = {115405},
doi = {10.1016/j.ejca.2025.115405},
pmid = {40239400},
issn = {1879-0852},
abstract = {INTRODUCTION: Metformin is frequently prescribed to treat type 2 diabetes. Its primarily regulates hepatic and colonic glucose metabolism, but recent studies have suggested an anti-inflammatory effect, especially in colitis. It has been suggested that metformin may enhance immune checkpoint inhibition (ICI) efficacy for cancer treatment. Our study aims to explore the impact of metformin on ICI efficacy and the risk for colitis.

METHODS: This was a single center, retrospective analysis of consecutive patients at a tertiary cancer center who received ICI between 01/2010-12/2022 and developed immune-mediated colitis (IMC). Patients were screened for colitis based on stool tests, then divided into two groups depending on metformin use prior to colitis onset. We collected data on demographic and colitis clinical information including treatments, and outcomes.

RESULTS: A total of 953 patients were included. The incidence of IMC was higher among metformin users (7.6 %) than non-metformin users (4.9 %; p < 0.01). There were no significant differences in colitis features and outcomes, except for longer hospital stay among metformin users (8 days vs 6 for non-metformin users; p = 0.03). Metformin use was associated with shorter overall survival vs non-metformin users among patients with IMC (p = 0.03).

DISCUSSION: Our study is among the first to explore the impact of metformin on IMC and overall survival. We found that metformin use may be associated with higher risk of IMC. We also found an association between metformin use and shorter overall survival among patients who developed IMC. Larger studies with risk-stratified analysis are needed to validate our findings.},
}

@article {pmid40239123,
year = {2025},
author = {Giri, VN and Rumble, RB and Yu, EY and Lu, K},
title = {Germline and Somatic Genomic Testing for Metastatic Prostate Cancer: ASCO Guideline Clinical Insights.},
journal = {JCO oncology practice},
volume = {},
number = {},
pages = {OP2500186},
doi = {10.1200/OP-25-00186},
pmid = {40239123},
issn = {2688-1535},
}

@article {pmid40233328,
year = {2025},
author = {Annesley, C and Seidel, KD and Wu, Q and Summers, C and Wayne, AS and Pulsipher, MA and Agrawal, AK and Brown, CT and Mgebroff, S and Lindgren, CG and Rawlings-Rhea, SD and Huang, W and Wilson, A and Jensen, MC and Park, JR and Gardner, RA},
title = {Outcomes of PLAT-02 and PLAT-03: Evaluating CD19 CAR T-Cell Therapy and CD19-expressing T-APC Support in Pediatric B-ALL.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2025028359},
pmid = {40233328},
issn = {1528-0020},
abstract = {This study reports outcomes of PLAT-02, a phase 2 trial of SCRI-CAR19, a second-generation CAR T-cell product with FMC63 scFv and 41BB costimulation, in pediatric and young adult patients with B-cell acute lymphoblastic leukemia; and PLAT-03, a companion study evaluating exogenous CD19 antigen stimulation with serial infusions of T cells expressing truncated CD19, T-cell antigen presenting cells (T-APCs). The efficacy cohort of PLAT-02 (n=72 patients, median age 12.5 years) received fludarabine/cyclophosphamide lymphodepletion followed by a dose of 1X106 CAR+ T cells/kg. MRD-negative complete remission rate was 89%. Leukemia free survival (LFS) with 95% CI at 1 and 2 years was 0.71 (0.58, 0.81) and 0.64 (0.51, 0.75). Patients with low disease burden had significantly higher 1-year LFS (0.91 vs. 0.42). Rapid in vivo contraction of CAR T cells after infusion was associated with CAR loss within six months compared to those without rapid contraction (57% vs. 19%, respectively). Most common grade 3/4 adverse events included cytokine release syndrome in 13% and neurotoxicity in 16%. The companion pilot, PLAT-03, enrolled 26 patients, and 19 received T-APCs. Neither cytokine-release syndrome nor neurotoxicity were observed after T-APC infusion. T-APC infusion in patients improved persistence (P=0.03) with rapid CAR T-cell contraction was associated with decreased early CAR loss (20% with T-APC vs. 57% without). Further exploration of serial artificial CD19 antigen exposure is warranted based on these pilot results. PLAT-02 (NCT02028455) and PLAT-03 (NCT03186118).},
}

@article {pmid40228175,
year = {2025},
author = {Subbiah, V and Othus, M and Palma, J and Cuglievan, B and Kurzrock, R},
title = {Designing Clinical Trials for Patients With Rare Cancers: Connecting the Zebras.},
journal = {American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting},
volume = {45},
number = {3},
pages = {e100051},
doi = {10.1200/EDBK-25-100051},
pmid = {40228175},
issn = {1548-8756},
mesh = {Humans ; *Neoplasms/therapy/diagnosis/genetics ; *Clinical Trials as Topic/methods ; *Rare Diseases/therapy/diagnosis ; Precision Medicine ; *Research Design ; },
abstract = {The field of rare cancer research is rapidly transforming, marked by significant progress in clinical trials and treatment strategies. Rare cancers, as defined by the National Cancer Institute, occur in fewer than 150 cases per million people each year, yet they collectively represent a significant portion of all cancer diagnoses. Because of their infrequency, these cancers pose distinct challenges for clinical trials, including limited patient populations, geographical dispersion, and a general lack of awareness of treatment options. Economic limitations further complicate drug development, making initiatives such as the Orphan Drug Act essential for incentivizing research. The advent of next-generation sequencing (NGS) and precision medicine has been instrumental in identifying actionable genetic alterations in parallel with an explosion in the development of genomically targeted therapies, immunotherapies, and antibody drug conjugates. Advances in clinical NGS, precision medicine, and tumor-agnostic therapies have become central to the progress in rare cancer research. The development and approval of tumor-agnostic drugs, such as BRAF, NTRK, and RET inhibitors, and immunotherapy for mismatch repair deficient/microsatellite instability-high status cancers highlight the potential of personalized treatments across diverse cancer types and across the age spectrum. Collaborative trials from cooperative groups including SWOG DART, ASCO TAPUR, NCI-MATCH, pediatric COG-match, DRUP, IMPRESS, and innovative registrational basket and platform trials (eg, VE-Basket, ROAR, LIBRETTO-001, ARROW), along with patient advocacy group-run trials like TRACK, are enhancing access to clinical trials. In addition, artificial intelligence has the potential to improve the trial matching process. An integrated approach, combining these innovations in collaboration with multiple stakeholders, is crucial for advancing rare cancer research, offering hope for better patient outcomes and quality of life.},
}

Humans
*Neoplasms/therapy/diagnosis/genetics
*Clinical Trials as Topic/methods
*Rare Diseases/therapy/diagnosis
Precision Medicine
*Research Design

@article {pmid40227208,
year = {2025},
author = {Kaaks, R and Cooley, V and Mukama, T and Teras, LR and Patel, AV and Masala, G and Crous-Bou, M and Harris, HR and Langseth, H and Surcel, HM and Wentzensen, N and Terry, K and Sasamoto, N and Tworoger, S and Fortner, RT},
title = {A Prospective Study Consortium for the Discovery and Validation of Early Detection Markers for Ovarian Cancer ("PREDICT") - Baseline findings for CA125.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {},
number = {},
pages = {},
doi = {10.1158/1078-0432.CCR-24-1845},
pmid = {40227208},
issn = {1557-3265},
abstract = {PURPOSE: Epithelial ovarian cancer (EOC) is a lethal malignancy. CA125, the "best" available marker for detecting EOC, has insufficient sensitivity and specificity for earlier-stage disease and is not a meaningful screening tool, motivating the search for further biomarkers. Cancer biomarker discovery is enhanced by "omics" technologies. Discovery studies for EOC biomarkers should be conducted in pre-diagnosis blood samples from prospective cohorts to maximize likelihood of identifying markers that can detect disease before usual diagnosis and in earlier disease stage, while reducing methodologic biases.

EXPERIMENTAL DESIGN: Individual cohorts with pre-diagnosis blood samples have insufficient sample size for such studies. thus, we established "PREDICT" ("Prospective Early Detection Consortium for Ovarian Cancer")-a collaboration of nine prospective studies-to assemble a sufficient number of EOC cases with blood samples collected ≤18 months before diagnosis plus controls. The 457 cases and 1,687 controls have circulating CA125 measured using a clinical assay.

RESULTS: The discrimination capacity for single CA125 measurements in samples collected <6 months prior to diagnosis was high (area under the curve (AUC), PREDICT overall=0.92; range across cohorts of non-pregnant individuals=0.89-0.98), and declined with extended time between blood collection and diagnosis. Between-cohort variability in CA125 levels and predictive performance was observed.

CONCLUSIONS: Ongoing investigations in PREDICT are evaluating the early detection potential of tumor-associated autoantibodies and microRNAs, using CA125 as a benchmark. PREDICT is a well-characterized resource for identifying and validating detection markers for EOC that may then be used in multi-modal screening, as a complement to CA125 and combined with imaging.},
}

@article {pmid40226958,
year = {2025},
author = {Heng, AK and Gooley, T and Lo, SS and Yang, JT and Gillespie, EF and Halasz, LM and Tseng, YD},
title = {The Impact of Race and Ethnicity on Location and Delivery of Palliative Radiotherapy.},
journal = {American journal of clinical oncology},
volume = {},
number = {},
pages = {},
doi = {10.1097/COC.0000000000001202},
pmid = {40226958},
issn = {1537-453X},
abstract = {OBJECTIVES: Among patients that underwent palliative RT (pRT) at a single institution, we evaluated whether differences exist across race and ethnicity in location of pRT consultation and delivery of pRT.

METHODS: This retrospective study included cancer patients aged 18 years or older who received pRT between 10/2021 and 10/2022. Logistic regression models were used to examine univariable (UVA) and multivariable (MVA) associations between race and pRT consult in the inpatient (vs. outpatient) setting. A subset analysis of quality metrics for pRT delivery was limited to patients who had outpatient consults for pain.

RESULTS: Four hundred forty patients underwent 548 pRT consults (104 inpatient and 444 outpatient) followed by a course of pRT. Most patients were male (58.2%), White non-Hispanic (WNH) (72.6%), and English-speaking (92.9%). On MVA adjusting for histology, language, and insurance type, consults for Black/African American (BAA) patients had 2.92 higher odds of being performed in the inpatient setting compared with consults for WNH patients (95% CI: 1.28-6.70, P=0.011), although the global P-value was P=0.217. Among 290 outpatient consults for painful lesions, no differences in time to pRT start (global P=0.84), number of prescribed fractions of RT (global P=0.94), or new prescriptions for opioids (global P=0.69) were noted by race and ethnicity.

CONCLUSIONS: In this study, BAA race was associated with the location of pRT consultation, but no discernible differences were noted regarding the outpatient delivery of pRT for pain. These findings support the importance of inpatient pRT programs to ensure equitable access. More research is needed to understand barriers to outpatient consult.},
}

@article {pmid40231215,
year = {2023},
author = {He, B and Phipps, W and Aboulafia, DM},
title = {Engaging Resource-Constrained Countries in Research Trials of HIV and Cancer: Lessons from Sub-Saharan Africa and the AIDS Malignancy Consortium.},
journal = {International journal of cancer care and delivery},
volume = {3},
number = {2},
pages = {},
pmid = {40231215},
issn = {2770-3533},
support = {UM1 CA121947/CA/NCI NIH HHS/United States ; },
abstract = {HIV contributes significantly to the global burden of cancer. In developing countries, AIDS-defining cancers predominate due to inconsistent access to antiretroviral therapy (ART). Even though AIDS-defining cancers are now less common in developed countries, the prevalence of non-AIDS-defining cancers (NADCs) has increased due to longer life expectancy in a milieu of chronic immune activation, exposure to oncogenic viruses, lifestyle factors, and environmental variables. In resource-constrained countries with inconsistent access to ART, Kaposi sarcoma, aggressive B-cell lymphomas, and cervical cancer continue to be a large problem. Not only do people living with HIV (PLWH) face higher cancer incidence and mortality, but they also encounter persistent stigmatization and barriers to equitable access to cancer treatment. To bridge this gap, the United States National Cancer Institute (NCI) established the AIDS Malignancy Consortium (AMC) to evaluate novel treatments, preventive strategies, and clinical guidelines for PLWH by conducting both domestic and international research. The AMC also emphasizes the development of robust research infrastructure in resource-limited countries, training of researchers, and fair management of clinical trial specimens. Despite various challenges, the AMC has contributed significant insights to international cancer trials among PLWH, thereby transforming clinical practice in low-resource areas. The high global burden of HIV-associated cancer underscores the need for comprehensive research, improved healthcare access, and greater inclusion of PLWH in cancer clinical trials.},
}

@article {pmid40224258,
year = {2025},
author = {Tereshchenko, LG and Haq, KT and Howell, SJ and Mitchell, EC and Hyde, J and Martínez, J and Ahmed, CA and Briceno, G and Patel, H and Pena, J and Khan, A and Soliman, EZ and Lima, JAC and Kapadia, SR and Misra-Hebert, AD and Kansal, MM and Daviglus, ML and Kaplan, R},
title = {Sex differences in global electrical heterogeneity: The Hispanic Community Health Study/Study of Latinos.},
journal = {Heart rhythm O2},
volume = {6},
number = {1},
pages = {97-102},
pmid = {40224258},
issn = {2666-5018},
}

@article {pmid40222449,
year = {2025},
author = {Alver, SK and Peters-Samuelson, BA and Mossavar-Rahmani, Y and Qi, Q and McClain, AC and Van Horn, L and Burk, RD and Kaplan, RC},
title = {Association of meal timing with adiposity measures and gut microbiome characteristics in a cohort study: the Hispanic Community Health Study/Study of Latinos.},
journal = {The American journal of clinical nutrition},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajcnut.2025.04.003},
pmid = {40222449},
issn = {1938-3207},
abstract = {BACKGROUND: Time-restricted eating may help control weight through caloric restriction, circadian rhythm, or influence on the gut microbiome (GMB). Physical activity (PA) also plays a role, as people with a longer eating window (EW: time between first and last daily intake) may be more active. The associations between meal timing, adiposity, PA, sedentary behavior (SB) and GMB characteristics are of interest in Hispanic/Latino persons, who experience a high burden of cardiometabolic diseases.

OBJECTIVE: We explored the relationship of EW with energy intake and accelerometer-measured activity and assessed whether a longer EW and later midpoint of intake (MOI: midpoint time of intake) are associated with adiposity and GMB differences in Hispanic/Latino adults.

METHODS: Using data from the prospective Hispanic Community Health Study/Study of Latinos (n=11,778 participants with valid 24-hour dietary recall and accelerometer data, no unplanned weight loss, and BMI ≥18.5; n=1925 with GMB data) we explored the relationship between EW, SB and energy intake. We used multivariable linear regression models to study the relationship between EW or MOI and adiposity measures and GMB characteristics, adjusted for clinical, behavioral, and demographic characteristics.

RESULTS: Those with longer EW tended to have less SB and greater energy intake, suggesting that some individuals may balance greater intake with greater expenditure. After adjustments including energy balance, each hour of EW was associated with 0.29% higher BMI (95% CI 0.07, 0.51), p=0.011. Longer EW and caloric EW (EWC: EW, caloric meals only) were associated with several obesity-associated GMB taxa, such as Streptococcus (enriched, β [95% CI] 0.04 [0.01, 0.07] for EW). MOI was not significantly associated with adiposity or GMB characteristics.

CONCLUSIONS: Shorter EW may promote healthy weight, but some individuals with longer vs shorter EWs tend to have greater activity that could balance their greater energy intake. EW and EWC may influence GMB characteristics.},
}

@article {pmid40221882,
year = {2025},
author = {Dima, D and Goel, U and Ullah, F and Faiman, B and Basali, D and Mazzoni, S and Williams, LS and Samaras, C and Valent, J and Anwer, F and Khouri, J and Raza, S},
title = {Presentation and Outcomes of Localized Immunoglobulin Light Chain Amyloidosis: 14-Year Experience of an Academic Center.},
journal = {Hematological oncology},
volume = {43},
number = {3},
pages = {e70082},
pmid = {40221882},
issn = {1099-1069},
mesh = {Humans ; Male ; Female ; *Immunoglobulin Light-chain Amyloidosis/therapy/mortality/diagnosis/pathology ; Middle Aged ; Aged ; Retrospective Studies ; Adult ; Aged, 80 and over ; Prognosis ; Survival Rate ; Academic Medical Centers ; Follow-Up Studies ; Treatment Outcome ; },
abstract = {Localized light chain amyloidosis (loc-AL) is a rare disorder characterized by localized deposition of misfolded AL fibrils. There are limited data on patterns of disease presentation and long-term outcomes. In this study, we retrospectively reviewed 146 patients with loc-AL at our institution between January 1, 2010, and March 1, 2024. We excluded patients with evidence of systemic AL amyloidosis. We calculated local (PFSL) and systemic (PFSs) progression free survival (PFS) and overall survival (OS) using the Kaplan-Meier method. We found that loc-AL most commonly involved the respiratory (26%), gastrointestinal (17%), head and neck (17%) and genitourinary (10%) systems. Overall, 51% patients were asymptomatic at presentation, and 16% had a co-existent autoimmune disease. First line management included observation (52%), surgical resection (39%), chemotherapy (3%), and radiation (2%). Most patients (59%) had a response with first-line therapy. The median PFSL was ∼15 years (10-year PFSL 68%), and median OS was not reached (10-year OS 83%). None of the patients had progression to systemic amyloidosis. Seventeen patients had local recurrence and required second line therapy. In conclusion, loc-AL has an excellent prognosis and does not progress to systemic AL amyloidosis. Observation and/or surgical removal are usually adequate first-line approaches; however, a small proportion of patients can relapse locally requiring repeated interventions for symptom control.},
}

Humans
Male
Female
*Immunoglobulin Light-chain Amyloidosis/therapy/mortality/diagnosis/pathology
Middle Aged
Aged
Retrospective Studies
Adult
Aged, 80 and over
Prognosis
Survival Rate
Academic Medical Centers
Follow-Up Studies
Treatment Outcome

@article {pmid40221372,
year = {2025},
author = {Lawrence, MG and Keerthikumar, S and Townley, SL and Clark, AK and Cuffe, GB and Laven-Law, G and Hanson, AR and Shrestha, RK and Knutson, TP and Richards, MG and Teng, L and Choo, N and Crumbaker, M and Joshua, AM and Corey, E and Nelson, PS and Dehm, SM and Risbridger, GP and Tilley, WD and Hickey, TE and Taylor, RA and Selth, LA},
title = {Reprogramming of Androgen Receptor Activity in Castration-resistant Prostate Cancer is Shaped by Truncated Variants.},
journal = {European urology focus},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.euf.2025.03.017},
pmid = {40221372},
issn = {2405-4569},
abstract = {BACKGROUND AND OBJECTIVE: Under the selective pressure of treatment, prostate cancer cells express constitutively active androgen receptor (AR) variants. Whether AR variants mediate therapy resistance remains contested, because they are often coexpressed with abundant full-length AR. Therefore, we sought to determine how truncated variants shape AR chromatin occupancy and responses to treatments in both the presence and absence of full-length AR.

METHODS: We used a cohort of patient-derived xenografts of metastatic prostate cancer with diverse AR alterations. Chromatin immunoprecipitation and RNA sequencing were used to compare the landscape of AR binding and transcriptomic features. We assessed responses to castration by castrating host mice and evaluated responses to bipolar androgen therapy by administering testosterone cypionate.

KEY FINDINGS AND LIMITATIONS: By profiling the AR cistrome, we identified a distinct group of tumours defined by ARv567es expression, a variant arising due to structural rearrangements of the AR gene. ARv567es-positive tumours also had a distinct epigenomic profile and altered transcriptional features, including loss of canonical AR-regulated gene signatures and elevated expression of AR-repressed genes. ARv567es-positive tumours were resistant to castration and bipolar androgen therapy. In tumours that coexpress full-length AR, this involves dampened transcriptional responses and disruption of the autoregulatory loop that modulates AR levels. Study limitations include the need for additional models of AR-driven prostate cancer.

The emergence of ARv567es via gene rearrangements causes transcriptional reprogramming and therapy resistance. This highlights ARv567es as a potential as a marker to guide treatment decisions.},
}

@article {pmid40216759,
year = {2025},
author = {Zhang, X and Brody, JA and Graff, M and Highland, HM and Chami, N and Xu, H and Wang, Z and Ferrier, KR and Chittoor, G and Josyula, NS and Meyer, M and Gupta, S and Li, X and Li, Z and Allison, MA and Becker, DM and Bielak, LF and Bis, JC and Boorgula, MP and Bowden, DW and Broome, JG and Buth, EJ and Carlson, CS and Chang, KM and Chavan, S and Chiu, YF and Chuang, LM and Conomos, MP and DeMeo, DL and Du, M and Duggirala, R and Eng, C and Fohner, AE and Freedman, BI and Garrett, ME and Guo, X and Haiman, C and Heavner, BD and Hidalgo, B and Hixson, JE and Ho, YL and Hobbs, BD and Hu, D and Hui, Q and Hwu, CM and Jackson, RD and Jain, D and Kalyani, RR and Kardia, SLR and Kelly, TN and Lange, EM and LeNoir, M and Li, C and Le Marchand, L and McDonald, MN and McHugh, CP and Morrison, AC and Naseri, T and , and O'Connell, J and O'Donnell, CJ and Palmer, ND and Pankow, JS and Perry, JA and Peters, U and Preuss, MH and Rao, DC and Regan, EA and Reupena, SM and Roden, DM and Rodriguez-Santana, J and Sitlani, CM and Smith, JA and Tiwari, HK and Vasan, RS and Wang, Z and Weeks, DE and Wessel, J and Wiggins, KL and Wilkens, LR and Wilson, PWF and Yanek, LR and Yoneda, ZT and Zhao, W and Zöllner, S and Arnett, DK and Ashley-Koch, AE and Barnes, KC and Blangero, J and Boerwinkle, E and Burchard, EG and Carson, AP and Chasman, DI and Ida Chen, YD and Curran, JE and Fornage, M and Gordeuk, VR and He, J and Heckbert, SR and Hou, L and Irvin, MR and Kooperberg, C and Minster, RL and Mitchell, BD and Nouraie, M and Psaty, BM and Raffield, LM and Reiner, AP and Rich, SS and Rotter, JI and Benjamin Shoemaker, M and Smith, NL and Taylor, KD and Telen, MJ and Weiss, ST and Zhang, Y and Heard-Costa, N and Sun, YV and Lin, X and Cupples, LA and Lange, LA and Liu, CT and Loos, RJF and North, KE and Justice, AE},
title = {Whole genome sequencing analysis of body mass index identifies novel African ancestry-specific risk allele.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {3470},
pmid = {40216759},
issn = {2041-1723},
support = {U01 HL054472/HL/NHLBI NIH HHS/United States ; U19 CA203654/CA/NCI NIH HHS/United States ; R01 DK075787/DK/NIDDK NIH HHS/United States ; F32 HL085989/HL/NHLBI NIH HHS/United States ; U01 HL072524/HL/NHLBI NIH HHS/United States ; I01 BX003340/BX/BLRD VA/United States ; P20 GM109036/GM/NIGMS NIH HHS/United States ; P01 CA134294/CA/NCI NIH HHS/United States ; U01 HG009088/HG/NHGRI NIH HHS/United States ; T32 HL007055/HL/NHLBI NIH HHS/United States ; R01 DK122503/DK/NIDDK NIH HHS/United States ; R35 CA197449/CA/NCI NIH HHS/United States ; R01 HL104135/HL/NHLBI NIH HHS/United States ; I01 BX004821/BX/BLRD VA/United States ; R01 HL133040/HL/NHLBI NIH HHS/United States ; R01 HL120393/HL/NHLBI NIH HHS/United States ; R01 AR048797/AR/NIAMS NIH HHS/United States ; U01 HG007416/HG/NHGRI NIH HHS/United States ; U01 HL054509/HL/NHLBI NIH HHS/United States ; R01 DK 122503//U.S. Department of Health & Human Services | NIH | Office of Extramural Research, National Institutes of Health (OER)/ ; U01 HL120393/HL/NHLBI NIH HHS/United States ; U01 HL089897/HL/NHLBI NIH HHS/United States ; R01 HL113338/HL/NHLBI NIH HHS/United States ; R01 DK135938/DK/NIDDK NIH HHS/United States ; R01 AG058921/AG/NIA NIH HHS/United States ; R01 HL142302/HL/NHLBI NIH HHS/United States ; R01 DK110113/DK/NIDDK NIH HHS/United States ; R01 NS058700/NS/NINDS NIH HHS/United States ; R01 DK107786/DK/NIDDK NIH HHS/United States ; R01 HL119443/HL/NHLBI NIH HHS/United States ; R01 HL105756/HL/NHLBI NIH HHS/United States ; R01 AI114555/AI/NIAID NIH HHS/United States ; U01 HL089856/HL/NHLBI NIH HHS/United States ; T32 HL129982/HL/NHLBI NIH HHS/United States ; R01 HL067348/HL/NHLBI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01 HL104608/HL/NHLBI NIH HHS/United States ; R01 AI132476/AI/NIAID NIH HHS/United States ; K08 HL136928/HL/NHLBI NIH HHS/United States ; M01 RR007122/RR/NCRR NIH HHS/United States ; KL2 TR002490/TR/NCATS NIH HHS/United States ; R01 HL142825/HL/NHLBI NIH HHS/United States ; R01 DK124097/DK/NIDDK NIH HHS/United States ; R01 HL093093/HL/NHLBI NIH HHS/United States ; I01 BX003362/BX/BLRD VA/United States ; R01 HL068959/HL/NHLBI NIH HHS/United States ; U01 HL072507/HL/NHLBI NIH HHS/United States ; R01 DK071891/DK/NIDDK NIH HHS/United States ; P01 HL132825/HL/NHLBI NIH HHS/United States ; R01 HG010297/HG/NHGRI NIH HHS/United States ; U01 HL054495/HL/NHLBI NIH HHS/United States ; R01 HL055673/HL/NHLBI NIH HHS/United States ; R01 HL092301/HL/NHLBI NIH HHS/United States ; U01 HL054473/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *Body Mass Index ; Polymorphism, Single Nucleotide ; *Whole Genome Sequencing ; Genome-Wide Association Study ; *Obesity/genetics/ethnology ; Male ; Female ; Alleles ; Genetic Predisposition to Disease ; *Black People/genetics ; Adult ; Middle Aged ; },
abstract = {Obesity is a major public health crisis associated with high mortality rates. Previous genome-wide association studies (GWAS) investigating body mass index (BMI) have largely relied on imputed data from European individuals. This study leveraged whole-genome sequencing (WGS) data from 88,873 participants from the Trans-Omics for Precision Medicine (TOPMed) Program, of which 51% were of non-European population groups. We discovered 18 BMI-associated signals (P < 5 × 10[-9]), including two secondary signals. Notably, we identified and replicated a novel low-frequency single nucleotide polymorphism (SNP) in MTMR3 that was common in individuals of African descent. Using a diverse study population, we further identified two novel secondary signals in known BMI loci and pinpointed two likely causal variants in the POC5 and DMD loci. Our work demonstrates the benefits of combining WGS and diverse cohorts in expanding current catalog of variants and genes confer risk for obesity, bringing us one step closer to personalized medicine.},
}

Humans
*Body Mass Index
Polymorphism, Single Nucleotide
*Whole Genome Sequencing
Genome-Wide Association Study
*Obesity/genetics/ethnology
Male
Female
Alleles
Genetic Predisposition to Disease
*Black People/genetics
Adult
Middle Aged

@article {pmid40215224,
year = {2025},
author = {Fisher, LH and Lazarus, E and Yu, C and Moodie, Z and Stieh, DJ and Yates, N and Zhang, L and Sawant, S and De Rosa, SC and Cohen, KW and Morris, D and Grant, S and Randhawa, A and Miner, MD and Hendriks, J and Wegmann, F and Gill, KM and Laher, F and Bekker, LG and Gray, GE and Corey, L and McElrath, MJ and Martin, T and Gilbert, PB and Tomaras, G and Walsh, SR and Baden, LR and , },
title = {ALVAC-prime and monomeric gp120 protein boost induces distinct HIV-1 specific humoral and cellular responses compared with adenovirus-prime and trimeric gp140 protein boost.},
journal = {PLOS global public health},
volume = {5},
number = {4},
pages = {e0004250},
pmid = {40215224},
issn = {2767-3375},
abstract = {Although clade-specific and cross-clade mosaic prime-boost HIV-1 vaccine regimens were advanced to the HVTN 702 and HVTN 705 efficacy trials, neither regimen prevented HIV acquisition. The respective Phase 1/2a studies, HVTN 100 (NCT02404311) and HVTN 117/HPX2004 (NCT02788045), provided rich immunological data, including previously identified correlates of risk, for comparing immune responses elicited by these vaccine regimens over time. We analyzed antibody responses measured by binding antibody multiplex assay, and CD4+ and CD8+ T-cell responses measured by intracellular cytokine staining in per-protocol vaccinees in HVTN 100 (n=186) vs. HVTN 117/HPX2004 (n=99) after the months 6 and 12 vaccinations (months 6.5/7 and 12.5/13), and 6 months after the last vaccination (month 18). At month 12.5/13, both regimens induced similarly high IgG breadth against gp120, gp140, and V1V2 antigens, and similar IgG responses to gp70-BCaseA V1V2. IgG V1V2 responses were more durable in HVTN 117/HPX2004, with the largest difference in the gp70-BCaseA V1V2 IgG response rate at month 18 (17.8% in HVTN 100 vs 61.9% in HVTN 117/HPX2004, p<0.001). IgG3 responses to consensus Env antigens were higher and more durable in HVTN117/HPX2004; for example, IgG3 response rate to the consensus gp140 antigen was 65.9% in HVTN 117/HPX2004 vs 6.3% in HVTN 100 at month 18 (TMLE p<0.0001). At month 18, both regimens induced similar IgG3 responses to gp70-BCaseA V1V2 (3.2% in HVTN 100 vs 1.1% in HVTN 117/HPX2004). Polyfunctional CD4+ Env was significantly higher in HVTN 100, and polyfunctional CD4+ Gag was higher in HVTN 117/HPX2004. CD8+ T-cell responses were not seen in HVTN 100, while CD8+ T-cell response rates in HVTN 117/HPX2004 reached up to 42%. Despite the distinct immune responses induced by the two HIV vaccine regimens, the lack of demonstrated efficacy suggests that broader, higher magnitude, and possibly qualitatively different immune responses are needed for protection against HIV acquisition. Trial registration: ClinicalTrials.gov NCT02404311 and NCT02788045; South African National Clinical Trials Registry (DOH-27-0215-4796).},
}

@article {pmid40214435,
year = {2025},
author = {Ramani, H and Cleret-Buhot, A and Sylla, M and Bunet, R and Bertrand, F and Peet, MM and Chartrand-Lefebvre, C and Trottier, B and Thomas, R and Routy, JP and Fortin, C and Martel-Laferrière, V and Sadouni, M and Cloutier, G and Allard, L and Kizer, JR and Chomont, N and Ancuta, P and Hanna, DB and Kaplan, RC and Jenabian, MA and Landay, AL and Durand, M and El-Far, M and Tremblay, CL},
title = {Opposite Roles of IL-32α Versus IL-32β/γ Isoforms in Promoting Monocyte-Derived Osteoblast/Osteoclast Differentiation and Vascular Calcification in People with HIV.},
journal = {Cells},
volume = {14},
number = {7},
pages = {},
pmid = {40214435},
issn = {2073-4409},
support = {R01 AG054324/AG/NIA NIH HHS/United States ; 2R01AG054324-08A1/NH/NIH HHS/United States ; },
mesh = {Humans ; *Interleukins/metabolism ; *Monocytes/metabolism/pathology/cytology ; *Osteoblasts/metabolism/pathology ; *Cell Differentiation ; *HIV Infections/complications/pathology/metabolism ; *Vascular Calcification/metabolism/pathology/complications ; Protein Isoforms/metabolism ; *Osteoclasts/metabolism/pathology/cytology ; Male ; Calcium/metabolism ; Transforming Growth Factor beta/metabolism ; Middle Aged ; Female ; },
abstract = {People with HIV (PWH) have an increased risk of developing cardiovascular disease (CVD). Our recent data demonstrated that the multi-isoform proinflammatory cytokine IL-32 is upregulated in PWH and is associated with arterial stiffness and subclinical atherosclerosis. However, the mechanisms by which IL-32 contributes to the pathogenesis of these diseases remain unclear. Here, we show that while the less expressed IL-32α isoform induces the differentiation of human classical monocytes into the calcium-resorbing osteoclast cells, the dominantly expressed isoforms IL-32β and IL-32γ suppress this function through the inhibition of TGF-β and induce the differentiation of monocytes into the calcium-depositing osteocalcin+ osteoblasts. These results aligned with the increase in plasma levels of osteoprotegerin, a biomarker of vascular calcification, and its association with the presence of coronary artery subclinical atherosclerosis and calcium score in PWH. These findings support a novel role for the proinflammatory cytokine IL-32 in the pathophysiology of CVD by increasing vascular calcification in PWH.},
}

Humans
*Interleukins/metabolism
*Monocytes/metabolism/pathology/cytology
*Osteoblasts/metabolism/pathology
*Cell Differentiation
*HIV Infections/complications/pathology/metabolism
*Vascular Calcification/metabolism/pathology/complications
Protein Isoforms/metabolism
*Osteoclasts/metabolism/pathology/cytology
Male
Calcium/metabolism
Transforming Growth Factor beta/metabolism
Middle Aged
Female

@article {pmid40212049,
year = {2025},
author = {Onwuka, JU and Zahed, H and Feng, X and Alcala, K and Erhunmwunsee, L and Williams, RM and Aldrich, MC and Ahluwalia, JS and Albanes, D and Arslan, AA and Bassett, JK and Brennan, P and Cai, Q and Chen, C and Dimou, N and Ferrari, P and Freedman, ND and Huang, WY and Jones, ME and Jones, MR and Kaaks, R and Koh, WP and Langhammer, A and Liao, LM and Malekzadeh, R and Milne, RL and Rohan, TE and Sánchez, MJ and Sheikh, M and Sinha, R and Shu, XO and Stevens, VL and Tinker, LF and Visvanathan, K and Wang, Y and Wang, R and Weinstein, SJ and White, E and Yuan, JM and Zheng, W and Johansson, M and Robbins, HA},
title = {Association between socioeconomic position and lung cancer incidence in 16 countries: a prospective cohort consortium study.},
journal = {EClinicalMedicine},
volume = {82},
number = {},
pages = {103152},
pmid = {40212049},
issn = {2589-5370},
abstract = {BACKGROUND: Studies have reported higher lung cancer incidence among groups with lower socioeconomic position (SEP). However, it is not known how this difference in lung cancer incidence between SEP groups varies across different geographical settings. Furthermore, most prior studies that assessed the association between SEP and lung cancer incidence were conducted without detailed adjustment for smoking. Therefore, we aimed to assess this relationship across world regions.

METHODS: In this international prospective cohort consortium study, we used data from the Lung Cancer Cohort Consortium (LC3), which includes 20 prospective population cohorts from 16 countries in North America, Europe, Asia, and Australia. Participants were enrolled between 1985 and 2010 and followed for cancer outcomes using registry linkages and/or active follow-up. We estimated hazard ratios (HRs) for the association between educational level (our primary measure of SEP, in 4 categories) and incident lung cancer using Cox proportional hazards models separately for participants with and without a smoking history. The models were adjusted for age, sex, cohort (when multiple cohorts were included), smoking duration, cigarettes per day, and time since cessation.

FINDINGS: Among 2,487,511 participants, 53,830 developed lung cancer during a 13.5-year median follow-up (IQR = 6.5-15.0 years). Among participants with a smoking history, higher education was associated with decreased lung cancer incidence in nearly every cohort after detailed smoking adjustment. By world region, this association was observed in North America (HR per one-category increase in education [HRtrend] = 0.88, 95% CI = 0.87-0.89), Europe (HRtrend = 0.89, 95% CI = 0.88-0.91), and Asia (HRtrend = 0.91, 95% CI = 0.86-0.96), but not in the Australian study (HRtrend = 1.02, 95% CI = 0.95-1.09). By histological subtype, education associated most strongly with squamous cell carcinoma and more weakly with adenocarcinoma (p-heterogeneity < 0.0001). Among participants who never smoked, there was no association between education and lung cancer incidence in any cohort (all p-trend > 0.05), except the USA Southern Community Cohort Study (HRtrend = 0.75, 95% CI = 0.62-0.90).

INTERPRETATION: Based on longitudinal data from 2.5 million participants from 16 countries, our findings suggest that higher educational attainment was associated with lower lung cancer risk among participants with a smoking history, but not among participants who never smoked. Limitations of our study include that cohort participants cannot fully represent the general populations of the geographical regions included, and education was the only measure of SEP consistently available across our consortium.

FUNDING: This study was supported in part by the National Cancer Institute (NCI), the Lung Cancer Research Foundation (LCRF), and the World Cancer Research Fund (WCRF).},
}

@article {pmid40211539,
year = {2025},
author = {Jennewein, MF and Schultz, MD and Beaver, S and Battisti, P and Bakken, J and Hanson, D and Akther, J and Zhou, F and Mohamath, R and Singh, J and Cross, N and Kasal, DN and Ykema, MR and Reed, S and Kalange, D and Cheatwood, IR and Tipper, JL and Foote, JB and King, RG and Silva-Sanchez, A and Harrod, KS and Botta, D and Gerhardt, A and Casper, C and Randall, TD and Lund, FE and Voigt, EA},
title = {Intranasal replicon SARS-CoV-2 vaccine produces protective respiratory and systemic immunity and prevents viral transmission.},
journal = {Molecular therapy : the journal of the American Society of Gene Therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ymthe.2025.04.007},
pmid = {40211539},
issn = {1525-0024},
abstract = {While mRNA vaccines have been effective in combating SARS-CoV-2, waning of vaccine-induced antibody responses and lack of vaccine-induced respiratory tract immunity contribute to ongoing infection and transmission. In this work, we compare and contrast intranasal (i.n.) and intramuscular (i.m.) administration of a SARS-CoV-2 replicon vaccine delivered by a nanostructured lipid carrier (NLC). Both i.m. and i.n. vaccines induce potent systemic serum neutralizing antibodies, bone marrow-resident IgG-secreting cells, and splenic T cell responses. The i.n. vaccine additionally induces robust respiratory mucosal immune responses, including SARS-CoV-2-reactive lung-resident memory T cell populations. As a booster following previous i.m. vaccination, the i.n. vaccine also elicits the development of mucosal virus-specific T cells. Both the i.m. and i.n. administered vaccines durably protect hamsters from infection-associated morbidity upon viral challenge, significantly reducing viral loads and preventing challenged hamsters from transmitting virus to naïve cagemates. This replicon-NLC vaccine's potent systemic immunogenicity, and additional mucosal immunogenicity when delivered i.n., may be key for combating SARS-CoV-2 and other respiratory pathogens.},
}

@article {pmid40210677,
year = {2025},
author = {Petty, LE and Chen, HH and Frankel, EG and Zhu, W and Downie, CG and Graff, M and Lin, P and Sharma, P and Zhang, X and Scartozzi, AC and Roshani, R and Landman, JM and Boehnke, M and Bowden, DW and Chambers, JC and Mahajan, A and McCarthy, MI and Ng, MCY and Sim, X and Spracklen, CN and Zhang, W and Preuss, M and Bottinger, EP and Nadkarni, GN and Loos, RJF and Chen, YI and Tan, J and Ipp, E and Genter, P and Emery, LS and Louie, T and Sofer, T and Stilp, AM and Taylor, KD and Xiang, AH and Buchanan, TA and Roll, K and Gao, C and Palmer, ND and Norris, JM and Wagenknecht, LE and Nousome, D and Varma, R and McKean-Cowdin, R and Guo, X and Hai, Y and Hsueh, W and Sandow, K and Parra, EJ and Cruz, M and Valladares-Salgado, A and Wacher-Rodarte, N and Rotter, JI and Goodarzi, MO and Rich, SS and Bertoni, A and Raffel, LJ and Nadler, JL and Kandeel, FR and Duggirala, R and Blangero, J and Lehman, DM and DeFronzo, RA and Thameem, F and Wang, Y and Gahagan, S and Blanco, E and Burrows, R and Huerta-Chagoya, A and Florez, JC and Tusie-Luna, T and González-Villalpando, C and Orozco, L and Haiman, CA and Hanis, CL and Rohde, R and Whitsel, EA and Reiner, AP and Kooperberg, C and Li, Y and Duan, Q and Lee, M and Correa-Burrows, P and Fried, SK and North, KE and McCormick, JB and Fisher-Hoch, SP and Gamazon, ER and Morris, AP and Mercader, JM and Highland, HM and Below, JE and , and , },
title = {Large-scale multi-omics analyses in Hispanic/Latino populations identify genes for cardiometabolic traits.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {3438},
pmid = {40210677},
issn = {2041-1723},
support = {R56 DK062370/DK/NIDDK NIH HHS/United States ; U01 HG007416/HG/NHGRI NIH HHS/United States ; R01 DK107786/DK/NIDDK NIH HHS/United States ; R01 DK062370/DK/NIDDK NIH HHS/United States ; R56 HG010297/HG/NHGRI NIH HHS/United States ; U01 HG011723/HG/NHGRI NIH HHS/United States ; U01 DK062370/DK/NIDDK NIH HHS/United States ; R01 HL142302/HL/NHLBI NIH HHS/United States ; R01 DK110113/DK/NIDDK NIH HHS/United States ; R01 DK101855/DK/NIDDK NIH HHS/United States ; R01HL142302//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; },
mesh = {Humans ; *Diabetes Mellitus, Type 2/genetics/ethnology/blood ; Genome-Wide Association Study ; *Hispanic or Latino/genetics ; Mendelian Randomization Analysis ; Male ; Genetic Predisposition to Disease ; Female ; Proteomics ; Cholesterol, HDL/genetics/blood ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Lipids/blood/genetics ; Membrane Proteins/genetics ; Triglycerides/blood ; Multiomics ; White ; },
abstract = {Here, we present a multi-omics study of type 2 diabetes and quantitative blood lipid and lipoprotein traits conducted to date in Hispanic/Latino populations (nmax = 63,184). We conduct a meta-analysis of 16 type 2 diabetes and 19 lipid trait GWAS, identifying 20 genome-wide significant loci for type 2 diabetes, including one novel locus and novel signals at two known loci, based on fine-mapping. We also identify sixty-one genome-wide significant loci across the lipid/lipoprotein traits, including nine novel loci, and novel signals at 19 known loci through fine-mapping. Next, we analyze genetically regulated expression, perform Mendelian randomization, and analyze association with transcriptomic and proteomic measure using multi-omics data from a Hispanic/Latino population. Using this approach, we identify genes linked to type 2 diabetes and lipid/lipoprotein traits, including TMEM205 and NEDD9 for HDL cholesterol, TREH for triglycerides, and ANXA4 for type 2 diabetes.},
}

Humans
*Diabetes Mellitus, Type 2/genetics/ethnology/blood
Genome-Wide Association Study
*Hispanic or Latino/genetics
Mendelian Randomization Analysis
Male
Genetic Predisposition to Disease
Female
Proteomics
Cholesterol, HDL/genetics/blood
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Lipids/blood/genetics
Membrane Proteins/genetics
Triglycerides/blood
Multiomics
White

@article {pmid40208630,
year = {2025},
author = {Zhao, Y and Gulati, R and Lange, J and Olivas-Martinez, A and Raoof, S and Zheng, Y and Feng, Z and Etzioni, R},
title = {Sensitivity Measures in Studies of Cancer Early Detection Biomarkers.},
journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1158/1055-9965.EPI-24-1849},
pmid = {40208630},
issn = {1538-7755},
abstract = {BACKGROUND: The sensitivity of a cancer screening biomarker to detect prevalent preclinical cancer drives screening benefit. Studies estimate sensitivity at different points in the biomarker development process. We examine how closely these estimates reflect the sensitivity to detect preclinical cancer (preclinical sensitivity).

METHODS: We posit that preclinical sensitivity is inversely proportional to the preclinical sojourn time. We simulate studies and estimates of sensitivity corresponding to the Early Detection Research Network's Phases of Biomarker Development. Sensitivity estimates based on clinically diagnosed cases (Phase 2, clinical sensitivity), archived-sample studies (Phase 3, archived-sample sensitivity), and prospectively screened cohorts (Phases 4 and 5, prospective empirical sensitivity) are defined and compared against the corresponding expected preclinical sensitivity.

RESULTS: Clinical sensitivity is generally optimistic. Archived-sample sensitivity is optimistic near clinical diagnosis but may be pessimistic at longer look-back intervals, with bias dependent also on test specificity. Prospective empirical sensitivity is optimistic when the sojourn time is long relative to the screening interval. Bias in prospective empirical sensitivity depends also on the frequency and accuracy of confirmation testing following a positive screening test.

CONCLUSIONS: Sensitivity estimates from different phases of biomarker development should be distinguished and labeled accordingly to facilitate realistic assessment of diagnostic performance and prediction of potential benefit.

IMPACT: Our study highlights the need for clearer terminology to describe sensitivity of cancer early detection biomarkers. We introduce new labels, explain biases in sensitivity estimates, and advocate for improved communication to enhance understanding of diagnostic test performance.},
}

@article {pmid40207620,
year = {2025},
author = {Gray, CN and Ashokkumar, M and Janssens, DH and Kirchherr, JL and Allard, B and Hsieh, E and Hafer, TL and Archin, NM and Browne, EP and Emerman, M},
title = {Integrator complex subunit 12 knockout overcomes a transcriptional block to HIV latency reversal.},
journal = {eLife},
volume = {13},
number = {},
pages = {},
pmid = {40207620},
issn = {2050-084X},
support = {DP1 DA051110/DA/NIDA NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; R61 DA047023/DA/NIDA NIH HHS/United States ; R01 AI143381/AI/NIAID NIH HHS/United States ; T32 AI083203/AI/NIAID NIH HHS/United States ; T32 AI 083203//National Institute of Allergy and Infectious Diseases/ ; R56 AI170226/AI/NIAID NIH HHS/United States ; 1UM1-A1-164567//National Institute of Allergy and Infectious Diseases/ ; },
mesh = {*Virus Latency/drug effects/genetics ; Humans ; *HIV-1/physiology/drug effects/genetics ; Virus Activation/drug effects ; *HIV Infections/virology ; *Transcription, Genetic ; Gene Knockout Techniques ; Heterocyclic Compounds, 4 or More Rings/pharmacology ; CD4-Positive T-Lymphocytes/virology ; },
abstract = {The latent HIV reservoir is a major barrier to HIV cure. Combining latency reversal agents (LRAs) with differing mechanisms of action such as AZD5582, a non-canonical NF-kB activator, and I-BET151, a bromodomain inhibitor is appealing toward inducing HIV-1 reactivation. However, even this LRA combination needs improvement as it is inefficient at activating proviruses in cells of people living with HIV (PLWH). We performed a CRISPR screen in conjunction with AZD5582 & I-BET151 and identified a member of the Integrator complex as a target to improve this LRA combination, specifically Integrator complex subunit 12 (INTS12). Integrator functions as a genome-wide attenuator of transcription that acts on elongation through its RNA cleavage and phosphatase modules. Knockout of INTS12 improved latency reactivation at the transcriptional level and is more specific to the HIV-1 provirus than AZD5582 & I-BET151 treatment alone. We found that INTS12 is present on chromatin at the promoter of HIV and therefore its effect on HIV may be direct. Additionally, we observed more RNAPII in the gene body of HIV only with the combination of INTS12 knockout with AZD5582 & I-BET151, indicating that INTS12 induces a transcriptional elongation block to viral reactivation. Moreover, knockout of INTS12 increased HIV-1 reactivation in CD4 T cells from virally suppressed PLWH ex vivo, and we detected viral RNA in the supernatant from CD4 T cells of all three virally suppressed PLWH tested upon INTS12 knockout, suggesting that INTS12 prevents full-length HIV RNA production in primary T cells. Finally, we found that INTS12 more generally limits the efficacy of a variety of LRAs with different mechanisms of action.},
}

*Virus Latency/drug effects/genetics
Humans
*HIV-1/physiology/drug effects/genetics
Virus Activation/drug effects
*HIV Infections/virology
*Transcription, Genetic
Gene Knockout Techniques
Heterocyclic Compounds, 4 or More Rings/pharmacology
CD4-Positive T-Lymphocytes/virology

@article {pmid40205614,
year = {2025},
author = {Villalobos, A and Lipman, PD and Beebe-Dimmer, J and Borrayo, EA and Briant, KJ and Bruegl, A and Dee, C and Chavez, S and Drake, B and Johnson, SS and Kikuchi, K and Leeman, J and Lowery, J and Mendoza, JA and Parker, M and Purvis, L and Wells Sittig, K and Thompson, HS and Wangen, M and Wheeler, SB},
title = {Synergies, partnership outcomes, and lessons learned: A qualitative evaluation of cancer center-coalition engagement.},
journal = {JNCI cancer spectrum},
volume = {},
number = {},
pages = {},
doi = {10.1093/jncics/pkaf038},
pmid = {40205614},
issn = {2515-5091},
abstract = {BACKGROUND: Nine National Cancer Institute (NCI)-Designated Cancer Centers received supplemental funding to expand community outreach and engagement (COE) activities through a partnership with Centers for Disease Control and Prevention (CDC)-funded comprehensive cancer control coalitions. This article reports on an evaluation of these awards focused on organizational relationship synergies and partnership outcomes.

METHODS: NCI, COE, and coalition representatives co-designed the evaluation, which involved document review and 18 semi-structured interviews with 16 COE and 19 coalition representatives. AI-generated interview transcripts were dual-coded in NVivo 20/R1.

RESULTS: The funding generated a diverse collection of projects and partnerships. COE-coalition synergies and lessons learned were evident in the following domains: infrastructure, community and partner engagement, data monitoring, and intervention implementation, evaluation, and dissemination. Outcomes of this funding initiative were evident in the following domains: strengthened partnerships, expanded knowledge, improved health or healthcare programs and policies, and thriving communities.

CONCLUSIONS: Fostering COE-coalition partnerships created opportunities to leverage synergies and build capacity for engagement across multiple domains, contributing to enhanced trust and implementation of interventions across the cancer continuum. The findings provide examples and lessons about synergistic opportunities for cancer centers and coalitions to capitalize on. Successful collaborative relationships were based on identifying shared goals and complimentary expertise and roles, sharing of financial and other resources, and a commitment to authentic and open dialogue. While modest and short-term, supplemental funding can strengthen organizational relationships and promote effective collaboration on community-facing activities; it can also lead to improved research engagement and translation of evidence to practice.},
}

@article {pmid40205312,
year = {2025},
author = {Elbur, AI and Donnell, D and Hosek, S and Dye, B and Velloza, J and Delany-Moretlwe, S and Celum, C},
title = {The Association Between Use of Adherence Support Interventions and Adherence to HIV Preexposure Prophylaxis Among Young South African and Zimbabwean Women in HPTN 082.},
journal = {AIDS and behavior},
volume = {},
number = {},
pages = {},
pmid = {40205312},
issn = {1573-3254},
support = {UM1-AI068619//National Institute of Allergy and Infectious Diseases/ ; UM1-AI068617//National Institute of Allergy and Infectious Diseases/ ; UM1-AI068613//National Institute of Allergy and Infectious Diseases/ ; T32AI007433//National Institute of Allergy and Infectious Diseases/ ; },
abstract = {We assessed the association between PrEP adherence support interventions and intracellular tenofovir-diphosphate (TFV-DP) levels, a biomarker for PrEP adherence, using data from 368 South African and Zimbabwean adolescent girls and young women enrolled in the HIV Prevention Trials Network 082 trial from 2016 to 2018. Group-based trajectory modeling identified trajectories of TFV-DP levels and adherence support interventions, including weekly two-way SMS and optional monthly adherence clubs. Two trajectories of TFV-DP levels were identified: a consistently low trajectory (N = 248, 67.4%, with consistent TFV-DP levels of 100 fmol/punch) and a high-decreasing trajectory (N = 120, 32.6%, with TFV-DP levels decreasing from approximately 900 to 500 fmol/punch). Two trajectories were also observed for adherence club attendance: consistently moderate (N = 249, 67.7%, attended approximately two out of three clubs in a three-month period) and low-increasing (N = 119, 32.3%). Similarly, SMS response patterns included a consistently high engagement group (N = 222, 66.1%), who responded to approximately 90% of messages, and a consistently low engagement group (N = 114, 33.9%). Women with consistently high SMS responses had higher odds of being in the high-decreasing TFV-DP levels trajectory group (Adjusted Odds Ratio [AOR]: 6.6; 95% CI 2.8-15.5; p < 0.001), while those with a consistently moderate adherence club attendance trajectory had an AOR of 1.3 (95% CI 0.5-3.3, p = 0.620) for being in the same group. Use of PrEP was aligned with the higher response trajectories of SMS responses but not with attendance to adherence support clubs.},
}

@article {pmid40203876,
year = {2025},
author = {Gilligan, T and Lin, DW and Adra, N and Bagrodia, A and Feldman, DR and Yamoah, K and Aggarwal, R and Chandrasekar, T and Costa, D and Drakaki, A and Eggener, S and Emamekhoo, H and Geynisman, DM and Graham, L and Humphrey, P and Leuva, H and Levine, EG and Luckenbaugh, A and Maughan, BL and McGregor, B and Monk, P and Picus, J and Pierorazio, P and Rais-Bahrami, S and Reichert, Z and Rwigema, JC and Saylor, P and Shah, A and Shah, S and Singla, N and Sircar, K and VanderWeele, D and Zhumkhawala, A and Montgomery, S and Sliker, B},
title = {NCCN Guidelines® Insights: Testicular Cancer, Version 2.2025.},
journal = {Journal of the National Comprehensive Cancer Network : JNCCN},
volume = {23},
number = {4},
pages = {},
doi = {10.6004/jnccn.2025.0018},
pmid = {40203876},
issn = {1540-1413},
mesh = {Humans ; *Testicular Neoplasms/therapy/diagnosis ; Male ; *Neoplasms, Germ Cell and Embryonal/therapy/diagnosis ; Seminoma/therapy/diagnosis ; *Medical Oncology/standards ; Neoplasm Staging ; },
abstract = {The NCCN Guidelines for Testicular Cancer provide recommendations for the multidisciplinary approach to the diagnostic workup, treatment, and follow-up for testicular germ cell tumors, including both seminoma and nonseminoma. These NCCN Guidelines Insights discuss the current treatment recommendations and supporting clinical data for seminomas as presented in Version 2.2025 of the NCCN Guidelines for Testicular Cancer.},
}

Humans
*Testicular Neoplasms/therapy/diagnosis
Male
*Neoplasms, Germ Cell and Embryonal/therapy/diagnosis
Seminoma/therapy/diagnosis
*Medical Oncology/standards
Neoplasm Staging

@article {pmid40203873,
year = {2025},
author = {Biermann, JS and Hirbe, A and Ahlawat, S and Bernthal, NM and Binitie, O and Boles, S and Brigman, B and Callan, AK and Cipriano, C and Cranmer, LD and Davis, J and Donnelly, E and Ferguson, M and Graham, A and Groundland, J and Hess, M and Hiniker, SM and Hoover-Regan, ML and Hornick, JL and Jonard, B and Kuechle, JB and Lindskog, D and Mayerson, JL and McGarry, SV and Morris, CD and Olson, D and Rose, PS and Santana, VM and Satcher, RL and Schwartz, H and Shulman, RM and Thorpe, SW and Wilky, BA and Wustrack, RL and Yoon, J and Hang, LE and Jones, F and Sansone, N and Lyons, M},
title = {Bone Cancer, Version 2.2025, NCCN Clinical Practice Guidelines In Oncology.},
journal = {Journal of the National Comprehensive Cancer Network : JNCCN},
volume = {23},
number = {4},
pages = {},
doi = {10.6004/jnccn.2025.0017},
pmid = {40203873},
issn = {1540-1413},
mesh = {Humans ; *Bone Neoplasms/therapy/diagnosis/mortality/pathology ; *Medical Oncology/standards/methods ; Combined Modality Therapy/methods ; *Sarcoma, Ewing/therapy/diagnosis ; *Osteosarcoma/therapy/diagnosis ; },
abstract = {Ewing sarcoma and osteosarcoma constitute 36% of all primary bone cancers. However, these 2 subtypes represent the most commonly diagnosed bone cancer types in the pediatric and adolescent population. Although still largely unknown, certain genetic mutations, rearrangements, and/or predisposition syndromes likely play a role in the pathogenesis of bone cancer. Osteosarcoma may also develop as a direct result of the long-term side effects of radiation therapy. With the implementation of a multimodality approach to treatment, including multiagent neoadjuvant and adjuvant chemotherapy regimens, targeted therapy options, surgery, and radiation, individuals with Ewing sarcoma and osteosarcoma are showing higher cure rates and improved overall survival. The NCCN Guidelines for Bone Cancer provide a consensus and evidence-based framework for the workup, management, and surveillance of local and recurrent/metastatic disease.},
}

Humans
*Bone Neoplasms/therapy/diagnosis/mortality/pathology
*Medical Oncology/standards/methods
Combined Modality Therapy/methods
*Sarcoma, Ewing/therapy/diagnosis
*Osteosarcoma/therapy/diagnosis

@article {pmid40203872,
year = {2025},
author = {Lerner, BA and Gupta, S and Burke, CA and Kupfer, S and Katona, BW and Grady, WM and Samadder, JJ and Yurgelun, MB and Kelly, KJ and Moreno Prats, M and Joseph, N and Idos, GE and Swanson, BJ and Kieber-Emmons, A and Weiss, JM and Llor, X},
title = {Advancing the Evaluation and Management of CDH1-Associated Gastric Cancer.},
journal = {Journal of the National Comprehensive Cancer Network : JNCCN},
volume = {23},
number = {4},
pages = {},
doi = {10.6004/jnccn.2025.7006},
pmid = {40203872},
issn = {1540-1413},
mesh = {Humans ; *Stomach Neoplasms/genetics/diagnosis/therapy/surgery/pathology ; Gastrectomy/methods ; *Cdh1 Proteins/genetics ; *Antigens, CD/genetics ; *Carcinoma, Signet Ring Cell/genetics/diagnosis/surgery/pathology ; Genetic Predisposition to Disease ; Germ-Line Mutation ; Cadherins ; },
abstract = {Gastric cancer is a significant global health concern, with CDH1-associated gastric cancer representing a small but important subset of cases. Historically, individuals with CDH1 pathogenic germline variants were advised to undergo prophylactic total gastrectomy due to the high reported risk of gastric cancer and the limited sensitivity of upper endoscopy in detecting signet ring cell carcinoma (SRCC). However, emerging data suggest that the cumulative lifetime risk of advanced gastric cancer among CDH1 germline pathogenic variant carriers is lower than previously thought, and early-stage SRCC detected on endoscopy does not necessarily indicate imminent-or even eventual-progression to advanced cancer. The near-universal presence of T1a SRCC in gastrectomy specimens from asymptomatic CDH1 pathogenic variant carriers calls into question the reflexive recommendation for gastrectomy, including upon detection of SRCC during surveillance. Furthermore, the morbidity and quality-of-life impact associated with total gastrectomy require careful consideration. Active endoscopic surveillance has shown promise as an alternative management strategy for gastrectomy in patients lacking indicators of >T1a SRCC, though current data are limited by short follow-up periods and selection bias. This review synthesizes recent findings on the natural history of CDH1-associated gastric cancer and evaluates the risks and benefits of gastrectomy versus active endoscopic surveillance, with the goal of helping clinicians provide personalized and evidence-based recommendations for patients with CDH1 pathogenic variants.},
}

Humans
*Stomach Neoplasms/genetics/diagnosis/therapy/surgery/pathology
Gastrectomy/methods
*Cdh1 Proteins/genetics
*Antigens, CD/genetics
*Carcinoma, Signet Ring Cell/genetics/diagnosis/surgery/pathology
Genetic Predisposition to Disease
Germ-Line Mutation
Cadherins

@article {pmid40203277,
year = {2025},
author = {Shadman, M and Brown, JR and Mohseninejad, L and Yang, K and Burnett, H and Neupane, B and Williams, R and Lamanna, N and O'Brien, SM and Tedeschi, A and Tam, CS},
title = {Comparative efficacy of Bruton tyrosine kinase inhibitors in high-risk relapsed/refractory CLL: a network meta-analysis.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2024014523},
pmid = {40203277},
issn = {2473-9537},
abstract = {Bruton tyrosine kinase inhibitors (BTKis) have led to changes in the treatment algorithm for patients with high-risk relapsed/refractory chronic lymphocytic leukemia (R/R CLL), defined based on the presence of genetic mutations. Given the lack of head-to-head trials comparing next-generation BTKis used to treat high-risk R/R disease, a network meta-analysis (NMA) was performed to estimate their relative efficacy. High-risk populations were defined based on the pre-specified definitions within each trial, including patients with del(17p) and/or TP53 mutations in ALPINE (n=150), and ASCEND (n=86), and del(17p)/del(11q) in ELEVATE-RR (n=533). Bayesian NMAs found zanubrutinib to be the most efficacious treatment for high-risk patients, with significantly reduced risk of progression or death compared with ibrutinib (hazard ratio [95% credible interval (CrI)]: 0.49 [0.31, 0.78]), acalabrutinib (0.55 [0.32, 0.94]), and bendamustine + rituximab or idelalisib + rituximab (BR/IR) (0.12 [0.05, 0.26]). Differences in overall survival demonstrated a numerical trend favoring zanubrutinib (probability better ≥80%) compared to ibrutinib (hazard ratio [95% credible interval]: 0.59 [0.31, 1.11]), acalabrutinib (0.72 [0.35, 1.50]) and BR/IR (0.65 [0.23, 1.75]). Rates of response also demonstrated trends favoring zanubrutinib compared to acalabrutinib, with significant results compared to ibrutinib. The NMA suggests that the most efficacious BTKi for patients with high-risk R/R CLL is zanubrutinib.},
}

@article {pmid40203192,
year = {2025},
author = {Yegya-Raman, N and Plastaras, JP and Wright, CM and Chelius, MR and Zhang, S and Baron, JA and Hubbeling, H and Sim, AJ and Robinson, TJ and Jain, MD and Imber, BS and Fregonese, B and Yahalom, J and Ladbury, C and Dandapani, S and Pinnix, CC and Gunther, JR and Fang, PQ and Wu, SY and Dabaja, BS and Yang, JC and Chew, J and Braunstein, S and Sinha, S and Denlinger, N and Sun, S and Terezakis, SA and Sakthivel, G and Constine, LS and Chowdhry, AK and Reagan, PM and Burke, S and Tseng, YD and LaRiviere, MJ and Maity, A and Schuster, SJ and Chong, EA and Figura, NB},
title = {Bridging Radiotherapy Prior to Chimeric Antigen Receptor T-Cells for B-Cell Lymphomas: An ILROG Multicenter Study.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025015855},
pmid = {40203192},
issn = {2473-9537},
abstract = {Despite the increasing utilization of bridging radiotherapy (Br-RT), its impact on chimeric antigen receptor T-cell therapy (CAR-T) efficacy and toxicity remains poorly characterized. We retrospectively reviewed patients with relapsed/refractory B-cell lymphomas (r/r BCL) who received Br-RT followed by CAR-T from 2018-2020 across 10 institutions. Br-RT toxicities were graded per CTCAE v5.0, and cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) per ASTCT Consensus Guidelines. 172 patients (168 large BCL, 3 mantle cell, 1 Burkitt) received Br-RT prior to axicabtagene ciloleucel (73%), tisagenlecleucel (23%), or brexucabtagene autoleucel (2%). At leukapheresis, most patients (74%) had advanced-stage disease and 39% had bulky disease measuring ≥10cm. Comprehensive Br-RT was administered to 39% (n=67) and bridging systemic therapy to 35% (n=60). Among all patients, grade ≥3 Br-RT toxicity occurred in 2% [one grade 5 toxicity], grade ≥3 CRS in 9%, and grade ≥3 ICANS in 24%. Median follow-up was 31.3 months. Two-year PFS and OS were 38% and 53%, respectively. On multivariable analysis, comprehensive Br-RT was associated with superior PFS (HR 0.38, p<0.001) and OS (HR 0.48, p=0.011). Patients with LDH normalization following Br-RT (high pre-Br-RT LDH, normal post-Br-RT LDH) had superior PFS and OS compared to those with high post-Br-RT LDH, and similar PFS and OS compared to those with normal baseline LDH. In this particularly high-risk cohort, Br-RT prior to CAR-T demonstrates an acceptable toxicity profile with favorable clinical outcomes when compared to historical controls. Comprehensive Br-RT and LDH normalization post-Br-RT may be associated with superior PFS and OS.},
}

@article {pmid40203190,
year = {2025},
author = {Kampouri, E and Flaherty, PW and Xie, H and Sekhon, MK and Chalal, C and Stevens-Ayers, TL and Green, DJ and Gauthier, J and Shadman, M and Pérez-Osorio, AC and Jerome, KR and Leisenring, WM and Boeckh, MJ and Hill, JA},
title = {The Impact of CMV Reactivation on Mortality After Chimeric Antigen Receptor T-Cell Therapy.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2024015164},
pmid = {40203190},
issn = {2473-9537},
}

@article {pmid39951615,
year = {2025},
author = {Pierson, SK and Brandstadter, JD and Torigian, DA and Bagg, A and Lechowicz, MJ and Alapat, D and Casper, C and Chadburn, A and Chandrakasan, S and Dispenzieri, A and Fosså, A and Hoffmann, C and Ide, M and Kurzrock, R and Mukherjee, S and Nasta, S and Navarro, JT and Noy, A and Oksenhendler, E and Bustamante, MS and Shyamsundar, S and Streetly, M and Wong, RSM and Zhang, L and Lim, MS and Srkalovic, G and van Rhee, F and Fajgenbaum, DC},
title = {Characterizing the heterogeneity of Castleman disease and oligocentric subtype: findings from the ACCELERATE registry.},
journal = {Blood advances},
volume = {9},
number = {8},
pages = {1952-1965},
doi = {10.1182/bloodadvances.2024014391},
pmid = {39951615},
issn = {2473-9537},
support = {R01 FD007632/FD/FDA HHS/United States ; R01 HL141408/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *Castleman Disease/diagnosis/pathology/etiology/classification/epidemiology ; Registries ; Female ; Male ; Adult ; Middle Aged ; Phenotype ; Aged ; Young Adult ; Adolescent ; },
abstract = {Castleman disease (CD) describes a group of rare lymphoproliferative disorders that exhibit a wide range of symptomatology and degree of lymphadenopathy, particularly across the 2 forms of CD with unknown etiology, unicentric CD (UCD), and human herpesvirus-8-negative/idiopathic multicentric CD (iMCD). Whereas UCD cases typically present with localized lymphadenopathy and mild symptoms, iMCD involves multicentric lymphadenopathy and cytokine storm-driven symptoms with 3 recognized clinical phenotypes. Increasingly, there are anecdotal reports of cases that do not fit into this framework, but these cases have not been systematically described. Herein, we use the ACCELERATE natural history registry to characterize the spectrum of CD based on disease features, symptomatology, and severity. Our results characterize a cohort of 179 CD cases, which were reviewed and confirmed by an expert panel of clinicians and hematopathologists. We show that patients with CD present on a continuous spectrum of clinical phenotypes, and we describe oligocentric CD (OligoCD), an intermediate phenotype that does not fit the criteria for UCD or iMCD. These cases tend to have "oligocentric" lymphadenopathy (median [interquartile range] regions of lymphadenopathy, 3.0 [2.0-4.0]) in a regional pattern and exhibit a mild clinical phenotype that is more similar to UCD than iMCD. We also show that patients with OligoCD are inconsistently categorized as UCD vs iMCD, highlighting the need for this characterization. Future data collected through ACCELERATE may further elucidate the natural history and risk profile of these patients.},
}

Humans
*Castleman Disease/diagnosis/pathology/etiology/classification/epidemiology
Registries
Female
Male
Adult
Middle Aged
Phenotype
Aged
Young Adult
Adolescent

@article {pmid40202852,
year = {2025},
author = {McQuoid, J and Blackwell, M and Bradley, D and Durazo, A and Frank-Pearce, SG and Heffner, JL and Islam, S and Le, M and Ling, PM and Pan, S and Raye, T and Tan, ASL and Vogel, EA and Wilson, M and Kendzor, DE},
title = {"It took me on a journey other than just to stop smoking": Pilot trial outcomes of an Empowerment Theory-based smoking cessation intervention for sexual and/or gender minoritized people in Oklahoma.},
journal = {Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco},
volume = {},
number = {},
pages = {},
doi = {10.1093/ntr/ntaf080},
pmid = {40202852},
issn = {1469-994X},
abstract = {INTRODUCTION: Sexual and/or gender minoritized (SGM) people are more likely to smoke if they live where SGM stigma is high, and existing SGM-tailored cessation interventions do not address unique challenges of these environments. This paper reports outcomes from a single-arm pilot trial of an Empowerment Theory-based smoking cessation intervention for SGM people living in high-stigma environments.

METHODS: SGM adults willing to quit smoking (N=20; Oklahoma) participated in a 12-week intervention comprised of online SGM-serving volunteer activity sessions concurrent with remotely-delivered smoking cessation support (i.e., behavioral support plus combination nicotine replacement therapy [NRT]). Baseline and exit surveys and in-depth exit interviews addressed retention, acceptability, engagement, and adherence.

RESULTS: Study retention was 80.0% (16/20). Most exit survey respondents attended ≥4 volunteer activity sessions (62.5%; 10/16) and ≥4 cessation counseling sessions (87.5%; 14/16), had moderate/high NRT adherence (patch 84.6%; 11/13 and gum/lozenge 76.9%; 10/13), and would recommend the intervention (81.3%; 13/16). At exit, 7-day point prevalence abstinence was self-reported by 45.0% (9/20; missing=smoking) of all participants and 56.3% (9/16) of exit survey respondents. At least half of participants reported pre-post intervention increases in perceived assertiveness and/or decreases in sexual identity acceptance concerns, concealment concerns, and internalized transphobia. Interviews identified intervention endorsement reasons, including experiencing greater belonging and hope.

CONCLUSION: A novel approach to SGM-tailored smoking cessation treatment that leveraged Empowerment Theory was feasible and acceptable. Future work should refine and adapt this intervention for other high-stigma places, test its efficacy and treatment mechanisms, and measure organizational and individual-level outcomes.

IMPLICATIONS: This study adds to the literature on culturally tailored smoking cessation interventions as the first tobacco intervention tailored for SGM people in high-stigma environments. It used a novel application of Empowerment Theory to advance SGM smoking cessation and resilience in the face of minority stress. Findings from this pilot study in Oklahoma indicate promising feasibility and acceptability and will inform future interventions to address tobacco use disparities among SGM people in high-stigma environments.},
}

@article {pmid40201647,
year = {2025},
author = {Dickson, E and Kuhlemeier, A and Adsul, P and Sanchez-Youngman, S and Myers, K and Akintobi, TH and Rosas, LG and Mendoza, JA and Oetzel, J and Castro-Reyes, P and Alaniz, C and Jacquez, B and Wallerstein, N},
title = {Developing the engage for equity institutional multi-sector survey: Assessing academic institutional culture and climate for community-based participatory research (CBPR).},
journal = {Journal of clinical and translational science},
volume = {9},
number = {1},
pages = {e44},
pmid = {40201647},
issn = {2059-8661},
abstract = {INTRODUCTION: Community-engaged research/community-based participatory research/patient-engaged research (CEnR/CBPR/PEnR) are increasingly recognized as important approaches for addressing health equity. However, there is limited support for CEnR/CBPR/PEnR within Academic Health Centers (AHCs). It is important for AHCs to measure and monitor the context, process, and policies in support for CEnR/CBPR/PEnR. The Engage for Equity (E2) team developed the first Institutional Multi-Sector Survey (IMSS) instrument to assess and explore CEnR/CBPR/PEnR-related practices at three AHCs.

METHODS: Working with "champion teams" consisting of academic leaders, researchers, and patient/community partners at each AHC, we developed the IMSS to assess the following domains: institutional mission, vision, and values; CEnR/CBPR/PEnR policies/practices; community processes/structures; function of formal community advisory boards; climate/culture for CEnR/CBPR; perceptions of institutional leadership for CEnR/CBPR/PEnR. The survey was piloted to a convenience sample of CEnR/CBPR/PEnR participants at each AHC site.

RESULTS: A sample aggregated across all sites consisting of community (n = 49) and academic (n = 50) participants perceived high levels of advocacy for CEnR/CBPR/PEnR among their AHC research teams. Participants indicated that institutional leadership supported CEnR/CBPR/PEnR in principle, but resources to build CEnR/CBPR/PEnR capacity at their respective institutions were lacking. Differences in responses from community and academic partners are summarized.

CONCLUSIONS: While limited by survey length and question adaptation, the findings contribute to identification of institutional barriers and facilitators to CEnR/CBPR/PEnR in AHCs. These findings are critically important to support and improve CEnR/CBPR/PEnR practice in academic institutions and to elevate community partner voices and needs for advancing community and patient partners' research.},
}

@article {pmid40201643,
year = {2025},
author = {Aschbrenner, KA and Walsh-Bailey, C and Brown, MC and Khan, T and Baggett, TP and Jones, SMW and Levy, DE and Pace, LE and Winickoff, JP},
title = {Practical considerations for engaging staff in resource-constrained healthcare settings in implementation research: A qualitative focus group and consensus building study.},
journal = {Journal of clinical and translational science},
volume = {9},
number = {1},
pages = {e65},
pmid = {40201643},
issn = {2059-8661},
abstract = {BACKGROUND: The primary purpose of this study was to assess perceived burdens and benefits of participating in implementation research among staff employed in resource-constrained healthcare settings. Another objective was to use findings to generate considerations for engaging staff in research across different phases of implementation research.

METHODS: This qualitative focus group and consensus building study involved researchers affiliated with the National Cancer Institute Implementation Science Centers in Cancer Control program and nine Community Health Centers (CHCs) in Massachusetts. Six focus groups (n = 3 with CHC staff; n = 3 with researchers) assessed barriers and facilitators to staff participation in implementation research. During consensus discussions, we used findings to develop considerations for engaging staff as participants and partners throughout phases of implementation research.

RESULTS: Sixteen researchers and 14 staff participated in separate focus groups; nine researchers and seven staff participated in separate consensus discussions. Themes emerged across participant groups in three domains: (1) influences on research participation; (2) research burdens and benefits; and (3) ways to facilitate staff participation in research. Practical considerations included: (a) aligning research with organizational and staff values and priorities; (b) applying user-centered design to research methods; (c) building organizational and individual research capacity; and (d) offering equitable incentives for staff participation.

CONCLUSIONS: Engaging staff as participants and partners across different phases of implementation research requires knowledge about what contributes to research burden and benefits and addressing context-specific burdens and benefits.},
}

@article {pmid40201639,
year = {2025},
author = {Briant, KJ and Adsul, P and Carosso, EA and Chakoian, M and Mapes, D and Coutee, T and Hempstead, B and Hassell, L and Law, W and Mendoza, JA},
title = {Adoption of E2PLUS tools and resources to promote the development of institutional capacity for patient-centered and community-engaged research at a cancer center.},
journal = {Journal of clinical and translational science},
volume = {9},
number = {1},
pages = {e72},
pmid = {40201639},
issn = {2059-8661},
abstract = {INTRODUCTION: The Fred Hutch/University of Washington/Seattle Children's Cancer Consortium's (Consortium) Office of Community Outreach & Engagement (OCOE) joined Stanford Medicine and Morehouse School of Medicine in implementing Engage for Equity Plus (E2PLUS), a multi-institutional community of practice to learn and share patient-centered and community-engaged research (P/CEnR) practices. University of New Mexico (UNM) facilitated this collaboration.

METHODS: The Consortium formed a Champion Team of 12 people who participated in two virtual workshops facilitated by UNM. Consortium executive leadership (n = 4) participated in interviews, and investigators (n = 4) and community members/patient advocates (n = 8) participated in focus groups to provide institutional context regarding P/CEnR. This is a paper on the process and findings.

RESULTS: Through E2PLUS engagement, the Champion Team identified four strategies to address institutional health inequities: 1) increase participation of underrepresented groups at all levels of institutional leadership and advisory boards; 2) create an Office of Patient Engagement to train and support patients who participate in institutional initiatives and advise research teams; 3) expand community engagement training, resources, and institutional commitment to focus on community-identified social and health needs; and 4) establish an umbrella entity for health equity efforts across the Consortium.

CONCLUSION: While the Consortium had longstanding community advisory boards and faculty and staff with P/CEnR expertise, it did not have centralized and institutionally supported P/CEnR resources, policies, and infrastructure. By participating in E2PLUS, the Champion Team received technical assistance to leverage qualitative data to influence strategies to guide the development of Consortium health equity infrastructure and capacity for P/CEnR in Washington.},
}

@article {pmid40200765,
year = {2025},
author = {Macris, PC and McMillen, K},
title = {Nutrition issues in adult hematopoietic cell transplantation: A narrative review of latest advances.},
journal = {Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition},
volume = {},
number = {},
pages = {},
doi = {10.1002/ncp.11288},
pmid = {40200765},
issn = {1941-2452},
abstract = {Patients undergoing hematopoietic cell transplantation (HCT) are a highly heterogenous population with respect to their unique nutrient requirements and need for nutrition support. Dose-intensive conditioning regimens in addition to the debilitating effects of graft-vs-host disease impact and adversely affect the transplant recipient's nutrition status. Decreased oral intake, increased nutrient requirements, and impaired nutrient absorption and utilization often necessitate specialized nutrition support. The use of parenteral nutrition and enteral nutrition support, as well as dietary intervention strategies for immunocompromised patients, have varied over the past five decades and are highly dependent on the type of transplant used. This review highlights adult nutrition assessment components, nutrition support practices, and management of complex nutrition consequences associated with HCT.},
}

@article {pmid40199861,
year = {2025},
author = {Chunara, F and Lugo, C and Osinski, K and Shah, MR and Shah, N and Kent, J and Mohyuddin, GR and Radhakrishnan, SV and Kaur, G and Chakraborty, R and Banerjee, R and Rasche, L and Schinke, C and D'Souza, A and Szabo, A and Mohan, M},
title = {Real-world treatment patterns for teclistamab and talquetamab in multiple myeloma (MM): experience from 609 patients.},
journal = {Blood cancer journal},
volume = {15},
number = {1},
pages = {61},
pmid = {40199861},
issn = {2044-5385},
}

@article {pmid40198924,
year = {2025},
author = {Chen, Y and Montaño, MA and Naik, P and Thuo, N and Kiptinness, C and Rafferty, M and Stergachis, A and Mugambi, ML and Ngure, K and Ortblad, KF and Sharma, M},
title = {Incremental cost of pre- and post-exposure prophylaxis service provision via an online pharmacy in Kenya.},
journal = {Journal of acquired immune deficiency syndromes (1999)},
volume = {},
number = {},
pages = {},
doi = {10.1097/QAI.0000000000003680},
pmid = {40198924},
issn = {1944-7884},
abstract = {BACKGROUND: Online pharmacy HIV pre- and post-exposure prophylaxis (PrEP/PEP) provision is a novel strategy to expand HIV prevention coverage. In the ePrEP pilot study, we found online pharmacy PrEP/PEP was feasible and reached populations at HIV risk in Kenya. However, program costs data are lacking.

METHODS: We conducted a costing within the ePrEP pilot study in Nairobi from 11/01/2022-12/29/2023. We obtained costs from expense reports and conducted time-and-motion observations and staff interviews. We estimated total and unit costs in the first year of implementation, cost per client and per PrEP client-month (2023 US Dollars (USD)).

RESULTS: Overall, 229 clients initiated PrEP (507 months of PrEP coverage) and 1320 initiated PEP. Based on observed program volume, annual financial cost was $109,945 USD (PrEP: $19,456; PEP: $90,489). Cost per client was higher for PrEP than PEP ($85 vs $68.6), and cost per PrEP client-month was $38 (mean duration: 2.2 months). Main drivers of financial costs were courier-delivery of HIV testing kits and drugs (PrEP: 50.6%; PEP: 40.5%), demand generation (PrEP: 25.9%; PEP: 32.1%), and equipment, system development, and utilities (PrEP: 9.3%; PEP: 9.8%). Assuming a scaled-up client volume of 2500 (PrEP: 370; PEP: 2130) reduced per-client financial costs for PrEP ($65.5) and PEP ($56) and cost per PrEP client-month ($29.6).

CONCLUSIONS: Costs of online PrEP/PEP provision is likely higher than clinic-based PrEP. Implementing cost sharing models including charging clients for HIV testing and optimizing courier delivery routes can increase program efficiencies. Our cost estimates can inform economic evaluations of online PrEP/PEP delivery.},
}

@article {pmid40198877,
year = {2025},
author = {Tuazon, SA and Portuguese, AJ and Pont, MJ and Cowan, AJ and Cole, GO and Sather, BD and Song, X and Thomas, S and Wood, BL and Blake, ML and Works, MG and Shadman, M and Liang, EC and Wu, Q and Voutsinas, JM and Gooley, TA and Turtle, CJ and Till, BG and Coffey, DG and Maloney, DG and Riddell, SR and Green, DJ},
title = {A phase 1 trial of fully human BCMA CAR-T therapy for relapsed/refractory multiple myeloma with 5-year follow-up.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2024027681},
pmid = {40198877},
issn = {1528-0020},
abstract = {FCARH143, an autologous BCMA-targeted CAR-T therapy which incorporates a fully human BCMA-specific scFv and 4-1BB costimulatory domain, was evaluated in a phase 1 trial (NCT03338972) for relapsed/refractory multiple myeloma (RRMM). Patients were stratified by bone marrow (BM) plasma cell involvement (10-30% or >30%) and received lymphodepleting chemotherapy followed by escalating CAR-T cell doses (50×106 to 450×106). The primary endpoint was safety; secondary endpoints were overall response rate (ORR), duration of response (DOR), and progression-free survival (PFS). Among 28 enrolled patients, all underwent leukapheresis and successful CAR-T manufacturing, though three (11%) did not proceed to infusion. The 25 treated patients (median age 64 years) had a median of eight prior therapies, 80% were triple-class refractory, and 44% had extramedullary disease (EMD). Cytokine release syndrome (CRS) occurred in 84% (8% grade 3-4, no grade 5), and neurotoxicity in 24% (12% grade 3, no grade 4-5). No treatment-related deaths occurred. At a median follow-up of 67.3 months, treated patients had an ORR of 100%, including a stringent complete response in 64%. Median PFS and overall survival (OS) were 15.5 and 32.1 months, respectively. In an intention-to-treat analysis (median follow-up 69.6 months), the ORR was 89.3%, and OS was 30.2 months. FCARH143 demonstrated potent anti-myeloma activity with a 100% response rate and manageable toxicity, independent of disease burden or cytogenetic risk. Further evaluation in high-risk RRMM is warranted.},
}

@article {pmid40198850,
year = {2025},
author = {Li, YL and Langley, C and Emerman, M and Gross, JD},
title = {APOBEC3G Antagonism by Vif, or When Structure Meets Biological and Evolutionary Studies.},
journal = {Annual review of virology},
volume = {},
number = {},
pages = {},
doi = {10.1146/annurev-virology-092623-091351},
pmid = {40198850},
issn = {2327-0578},
abstract = {Restriction factors serve as innate host defenses against viruses and act as critical barriers to cross-species transmission. In response, viruses have evolved accessory proteins to counteract restriction factors, enabling evasion of innate immune responses. The interplay between primate APOBEC3G (A3G) and lentiviral virion infectivity factor (Vif) exemplifies a molecular arms race between a restriction factor and its viral antagonist. This review integrates evolutionary and functional analyses of this system, showing how genetic signatures of molecular arms races map onto high-resolution cryo-electron microscopy structures. However, A3G's interaction with Vif is not limited to the evolutionary dynamic interface, characterized by rapidly evolving residues under selective pressure, but also involves a conserved interface mediated by RNA binding that positions A3G for antagonism by Vif. These findings propose a model wherein Vif and potentially other viral antagonists target functional complexes using a dual strategy: leveraging both adaptive interfaces subject to evolutionary pressures and conserved interfaces that constrain host escape mechanisms.},
}

@article {pmid40198766,
year = {2025},
author = {Dima, D and Afrough, A and Goel, U and Grajales-Cruz, A and Khouri, J and Julian, K and Pasvolsky, O and Banerjee, R and Razzo, B and Ferreri, CJ and Vazquez Martinez, MA and Davis, JA and Sannareddy, A and Castaneda Puglianini, O and Raza, S and Portuguese, AJ and Gaballa, MR and Rana, M and Lieberman-Cribbin, A and DeJarnette, S and Gonzalez, R and Chen, A and Herr, MM and Mikkilineni, L and Hosoya, H and Ouchveridze, E and Kaur, G and Rossi, AC and Shune, L and Anwer, F and Lin, Y and Richard, S and Sborov, DW and Baz, RC and Garfall, A and Lee, HC and Anderson, LD and Cowan, AJ and Patel, KK and Voorhees, PM and Sidana, S and Hansen, DK and Atrash, S and Susanibar-Adaniya, SP},
title = {Teclistamab for Patients with Heavily Pretreated Relapsed/Refractory Multiple Myeloma and Renal Impairment.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025016059},
pmid = {40198766},
issn = {2473-9537},
abstract = {Outcomes of bispecific antibodies in patients with renal impairment (RI) are not well-characterized given the exclusion of these patients from clinical trials. Herein, we evaluated patients with relapsed/refractory multiple myeloma and RI treated with standard-of-care teclistamab. RI was defined as creatinine clearance (CrCl) <40mL/min. CrCl <30mL/min or dialysis dependence were defined as severe RI. Of the 384 included patients, 81 (21%) had RI, including 45 (18%) with severe RI, and 18 (5%) on dialysis. Patients with RI were more likely to be older (median age 71 vs. 67 years, p=0.002), and have a higher median number of prior lines of therapy (7 vs. 6, p=0.04). Rates and severity of cytokine release syndrome (51% vs. 59%, grade ≥3: 1.2% vs. 1%) and immune effector cell-associated neurotoxicity syndrome (16% vs. 13%; grade ≥3: 2.5% vs 2.6%) were similar in patients with and without RI, respectively. Patients with RI had higher baseline and day-30 post-teclistamab grade ≥3 anemia and grade ≥3 thrombocytopenia. Renal function did not worsen after teclistamab initiation in patients with RI outside of the context of disease progression. Overall response rate (52% vs. 56%, p=0.61) and survival outcomes (median progression-free survival: 4.6 vs. 6.5 months; p=0.62) were comparable in patients with and without RI, respectively, after a median follow-up of 9.9 months. No differences in overall survival or non-relapse mortality were noted. Our findings suggest that treatment with teclistamab is feasible in patients with RI including those on dialysis, with a similar safety and efficacy profile to patients without RI.},
}

@article {pmid40198713,
year = {2025},
author = {Ashokkumar, M and Hafer, TL and Felton, A and Archin, NM and Margolis, DM and Emerman, M and Browne, EP},
title = {A targeted CRISPR screen identifies ETS1 as a regulator of HIV-1 latency.},
journal = {PLoS pathogens},
volume = {21},
number = {4},
pages = {e1012467},
doi = {10.1371/journal.ppat.1012467},
pmid = {40198713},
issn = {1553-7374},
abstract = {Human Immunodeficiency virus (HIV) infection is regulated by a wide array of host cell factors that combine to influence viral transcription and latency. To understand the complex relationship between the host cell and HIV-1 latency, we performed a lentiviral CRISPR screen that targeted a set of host cell genes whose expression or activity correlates with HIV-1 expression. We further investigated one of the identified factors - the transcription factor ETS1, and found that it is required for maintenance of HIV-1 latency in both latently infected cell lines and in a primary CD4 T cell latency model. Interestingly, ETS1 played divergent roles in actively infected and latently infected CD4 T cells, with knockout of ETS1 leading to reduced HIV-1 expression in actively infected cells, but increased HIV-1 expression in latently infected cells, indicating that ETS1 can play both a positive and negative role in HIV-1 expression. CRISPR/Cas9 knockout of ETS1 in CD4 T cells from ART-suppressed people with HIV-1 (PWH) confirmed that ETS1 maintains transcriptional repression of the clinical HIV-1 reservoir. Transcriptomic profiling of ETS1-depleted cells from PWH identified a set of host cell pathways involved in viral transcription that are controlled by ETS1 in resting CD4 T cells. In particular, we observed that ETS1 knockout increased expression of the long non-coding RNA MALAT1 that has been previously identified as a positive regulator of HIV-1 expression. Furthermore, the impact of ETS1 depletion on HIV-1 expression in latently infected cells was partially dependent on MALAT1. Additionally, we demonstrate that ETS1 knockout resulted in enhanced abundance of activating modifications (H3K9Ac, H3K27Ac, H3K4me3) on histones located at the HIV-1 long terminal repeat (LTR), indicating that ETS1 regulates the activity of chromatin-targeting complexes at the HIV-1 LTR. Overall, these data demonstrate that ETS1 is an important regulator of HIV-1 latency that impacts HIV-1 expression through repressing MALAT1 expression and by regulating modification of proviral histones.},
}

@article {pmid40198382,
year = {2025},
author = {Jones, MK and Nicklawsky, A and Shortt, J and Pattee, J and Kennerley, V and Eule, CJ and Candelario, N and , and O'Donnell, PH and Flaig, TW},
title = {Pharmacogenomics of chemotherapy induced peripheral neuropathy using an electronic health record-derived definition: a genome-wide association study.},
journal = {Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer},
volume = {33},
number = {5},
pages = {362},
pmid = {40198382},
issn = {1433-7339},
support = {University of Colorado Cancer Center Support Grant P30CA04934//University of Colorado/ ; },
mesh = {Humans ; Genome-Wide Association Study ; *Peripheral Nervous System Diseases/chemically induced/genetics ; Female ; Male ; Electronic Health Records ; Middle Aged ; *Antineoplastic Agents/adverse effects/administration & dosage ; Aged ; Pharmacogenetics ; Genetic Predisposition to Disease ; Bridged-Ring Compounds/adverse effects/administration & dosage ; Taxoids/adverse effects/administration & dosage ; Adult ; *Neoplasms/drug therapy ; Polymorphism, Single Nucleotide ; Vinca Alkaloids/adverse effects/administration & dosage ; },
abstract = {PURPOSE: Prior studies evaluating the genetic predisposition to chemotherapy induced peripheral neuropathy (CIPN) have been limited by small populations due to difficulty with real-world data extraction. This genome-wide association study (GWAS) evaluates the genetic differences between patients who developed CIPN against those unaffected, using an electronic health record (EHR) definition of CIPN.

METHODS: This study included all patients who received chemotherapy associated with CIPN and had germline genetic data within the biobank at the Colorado Center for Personalized Medicine. CIPN was defined by a new neuropathic pain medication or an ICD-diagnosis of neuropathy after specified chemotherapy initiation. GWAS were stratified by (1) total population, (2) platinum chemotherapy, (3) taxane chemotherapy, and (4) vinca alkaloid chemotherapy. Genes previously associated with CIPN were analyzed within each GWAS.

RESULTS: Nine hundred fifteen patients received chemotherapy associated with CIPN, with 528 patients (57%) developing CIPN. Median age at chemotherapy initiation was 60.5 years; female sex (n = 517, 56.5%) and White or Caucasian race (n = 822, 89.8%) were most common. Among single nucleotide polymorphisms (SNPs) that reached suggestive levels of genome-wide significance (p < 1 × 10[-5]), 60 SNPs occurred within 11 genes that may play a role in the development of or protection against CIPN, including RCOR1, CLDN14, TRIM5, and TMC2. No SNPs previously associated with CIPN achieved genome-wide significance in this population.

CONCLUSION: This pharmacogenomic study suggests several genomic loci that may modulate the development of CIPN. This EHR-definition may allow for increased sample sizes and improved statistical power in future genetic studies of CIPN.},
}

Humans
Genome-Wide Association Study
*Peripheral Nervous System Diseases/chemically induced/genetics
Female
Male
Electronic Health Records
Middle Aged
*Antineoplastic Agents/adverse effects/administration & dosage
Aged
Pharmacogenetics
Genetic Predisposition to Disease
Bridged-Ring Compounds/adverse effects/administration & dosage
Taxoids/adverse effects/administration & dosage
Adult
*Neoplasms/drug therapy
Polymorphism, Single Nucleotide
Vinca Alkaloids/adverse effects/administration & dosage

@article {pmid40197896,
year = {2025},
author = {Kantarjian, H and Zhai, Y and Oehler, VG and Jamy, O and Koller, PB and Haddad, FG and Sasaki, K and Jabbour, EJ},
title = {Olverembatinib in chronic myeloid leukemia-Review of historical development, current status, and future research.},
journal = {Cancer},
volume = {131},
number = {8},
pages = {e35832},
doi = {10.1002/cncr.35832},
pmid = {40197896},
issn = {1097-0142},
support = {//Ascentage Pharma Group Corp Ltd. (Hong Kong)/ ; },
mesh = {Humans ; *Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy/genetics ; *Protein Kinase Inhibitors/therapeutic use/pharmacology ; Drug Resistance, Neoplasm/genetics/drug effects ; Fusion Proteins, bcr-abl/genetics/antagonists & inhibitors ; Mutation ; *Antineoplastic Agents/therapeutic use ; Clinical Trials as Topic ; },
abstract = {Once considered an incurable disease with a poor prognosis (median survival, 3-6 years), chronic myeloid leukemia (CML) is now managed with a diverse clinical armamentarium that includes BCR::ABL1 tyrosine kinase inhibitors (TKIs), which have largely normalized life expectancy in most patients in the chronic phase of the disease (CML-CP). Clinical challenges remain, including ABL1 mutation-driven treatment resistance (under the selection pressures exerted by TKIs), as well as treatment intolerance, which can involve potentially serious arterial occlusive events. Olverembatinib is a third-generation TKI approved in China for TKI-resistant CML-CP and accelerated-phase CML with the T135I mutation, as well as for CML-CP resistant to or intolerant of first- and/or second-generation TKIs. Olverembatinib exhibits a broad coverage of ABL1 mutants, including the gatekeeper T315I variant and compound mutations. In preclinical models, olverembatinib inhibited multiple downstream protein kinases, which has potentially opened avenues for future management of other malignancies, including acute myeloid and lymphoid leukemias, gastrointestinal tumors, and others. The pharmacokinetic profile of olverembatinib is compatible with alternate-day dosing. In clinical trials, olverembatinib exerted potent antileukemic effects in heavily pretreated patients with CML, including those with ponatinib or asciminib resistance or intolerance, and was well tolerated. Future studies include the phase 3 registrational POLARIS-1 (NCT06051409; in patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia), POLARIS-2 (NCT06423911; in patients with CML with or without the T315I mutation), and POLARIS-3 (NCT06640361; in patients with succinate dehydrogenase-deficient gastrointestinal stromal tumors) clinical trials.},
}

Humans
*Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy/genetics
*Protein Kinase Inhibitors/therapeutic use/pharmacology
Drug Resistance, Neoplasm/genetics/drug effects
Fusion Proteins, bcr-abl/genetics/antagonists & inhibitors
Mutation
*Antineoplastic Agents/therapeutic use
Clinical Trials as Topic

@article {pmid40195948,
year = {2025},
author = {Sandfort, TGM and Szydlo, D and Fogel, JM and Chimwaza, Y and Rinnooy Kan, CE and Hamilton, EL and Mudhune, V and Panchia, R and Reynolds, D},
title = {Gaps in HIV Treatment and Care Cascade Among Men and Transfeminine Persons Who Have Sex with Men in Kenya, Malawi, and South Africa: Findings from the HIV Prevention Trials Network 075 Study (2015-2017).},
journal = {AIDS patient care and STDs},
volume = {},
number = {},
pages = {},
doi = {10.1089/apc.2025.0028},
pmid = {40195948},
issn = {1557-7449},
abstract = {Improving HIV outcomes for men who have sex with men (MSM) in sub-Saharan Africa requires addressing gaps in the HIV treatment cascade. This study examined these gaps among 71 treatment-naive MSM with HIV in the HIV Prevention Trials Network 075, a 1-year prospective biobehavioral cohort study (2015-2017) across four sub-Saharan African sites. Following a positive diagnosis, 86% of participants sought HIV care. Reasons for not having sought care or delays included a lack of perceived health issues and practical challenges. Most participants (80%) who engaged in care were prescribed antiretroviral therapy (ART). Although self-reported adherence was high, over one-third of those prescribed ART had no detectable antiretroviral drugs (ARVs) at the study's conclusion. ARV detection was significantly associated with study site, higher income, and experienced homophobia. The highest adherence rates were observed at the site offering direct, integrated treatment, underscoring the potential of "one-stop shop" services to mitigate intra-, interpersonal, and structural barriers. Despite a supportive study environment, gaps remain in linking MSM and transfeminine individuals to sustained HIV care and ART adherence. Given the urgency of addressing HIV among these populations, targeted interventions that promote engagement in care and adherence to treatment are critical.},
}

@article {pmid40193202,
year = {2025},
author = {Zhang, X and Scadden, AW and Marthi, A and Buchanan, VL and Qu, Y and Ferrier, KR and Chen, BD and Graff, M and Avila, J and Boerwinkle, E and Buyske, S and Clish, CB and Cruz, D and Fornage, M and Gerzsten, RE and Gignoux, CR and Glover, L and Hou, L and Justice, AE and Kooperberg, C and Kramer, H and Lange, L and Loos, RJF and Matise, T and Mychaleckyj, JC and Olabisi, OA and Peters, U and Raffield, LM and Reiner, AP and Rich, SS and Rotter, JI and Taylor, KD and Yu, B and Zheng, Y and North, KE and Mottl, AK and Highland, HM and Stanislawski, MA},
title = {Alterations in DNA Methylation, Proteomic, and Metabolomic Profiles in African Ancestry Populations with APOL1 Risk Alleles.},
journal = {Journal of the American Society of Nephrology : JASN},
volume = {},
number = {},
pages = {},
doi = {10.1681/ASN.0000000688},
pmid = {40193202},
issn = {1533-3450},
abstract = {BACKGROUND: The APOL1 high-risk haplotype has been associated with chronic kidney disease (CKD) and the deterioration of kidney function, particularly in populations with West African ancestry. However, the mechanisms by which APOL1 risk variants increase the risk for kidney disease and its progression have not been fully elucidated.

METHODS: We compared methylation (N = 3,191; 715 [22%] carriers), proteomic (N = 1,240; 169 [14%] carriers), and metabolomic (N = 6,309; 674 [11%] carriers) profiles in African and Hispanic/Latino carriers of two APOL1 high-risk alleles (G1/G1, G2/G2, G1/G2) and non-carriers (G0/G0), excluding heterozygotes (G0/G1, G0/G2), from the PAGE Consortium and UK BioBank. In each study, the associations between the APOL1 high-risk haplotype and up to 722,719 CpG sites, 2,923 proteins, or 836 metabolites were estimated using covariate-adjusted linear regression models, followed by fixed-effects sample size weighted meta-analyses.

RESULTS: Significant associations were observed between APOL1 high-risk haplotype and methylation at 52 CpG sites, with 48 located on chromosome 22 and 18 in the vicinity of APOL1 - 4 and MYH9. All significant CpG sites near APOL2 were hypomethylated, whereas those near APOL3 and APOL4 were hypermethylated. APOL1-associated CpG sites were also identified in genes involved in ion transport and mitochondrial stress pathways. Sensitivity analyses indicated consistent yet attenuated effects among heterozygotes, supporting an additive effect of APOL1 risk alleles. Further analyses of the 52 CpG sites identified two near APOL4 exhibiting G1-specific effects, eight associated with CKD but none with eGFR, and three showing heterogeneity by CKD status. Additionally, carrying two APOL1 risk alleles was associated with higher plasma APOL1 protein (β = 1.12, PFDR = 2.26e-70) and lower C18:1 cholesteryl ester metabolite (Z = -4.50, PFDR = 4.83e-3).

CONCLUSIONS: Our results demonstrate differential methylation, proteomic, and metabolomic profiles associated with APOL1 high-risk haplotypes.},
}

@article {pmid40191562,
year = {2024},
author = {Chintsanya, M and Talham, C and Zhang, B and Taylor, TE and Seydel, KB},
title = {Vital Sign alterations within 24 hours prior to death in children with retinopathy-positive Cerebral Malaria at Queen Elizabeth Central Hospital Malawi.},
journal = {Malawi medical journal : the journal of Medical Association of Malawi},
volume = {36},
number = {2},
pages = {128-133},
pmid = {40191562},
issn = {1995-7270},
mesh = {Humans ; *Malaria, Cerebral/mortality/complications/diagnosis/physiopathology ; Male ; Female ; Malawi/epidemiology ; Retrospective Studies ; Case-Control Studies ; Child, Preschool ; *Vital Signs ; Infant ; Child ; *Malaria, Falciparum/mortality/complications ; *Retinal Diseases/parasitology/mortality ; Coma ; },
abstract = {BACKGROUND: Malaria is a significant obstacle to child health and survival. Plasmodium falciparum infections, especially in children under five, lead to high morbidity and mortality. Cerebral malaria (CM) is a life-threatening complication characterized by coma, and its diagnosis can be improved by observing malarial retinopathy in children. Monitoring vital signs is essential for managing patients with CM.

OBJECTIVES: To determine if changes in vital signs predict death in children with retinopathy positive cerebral malaria (RPCM).

METHODS: This was a retrospective case-control study using data collected from children admitted to the Paediatric Research Ward at Queen Elizabeth Central Hospital in Blantyre between 1997 and 2020. Patients who died 24 hours or more after admission were matched with control patients who survived. Linear regression analyses were used to assess the differential time trends of each vital sign in the survivor group and death group. Classification models were used to quantify various vital signs' predictive power of death.

RESULTS: Among the population that died, the estimated change in average respiratory rate per hour approaching death was 0.02 breaths per minute compared to -0.25 breaths per minute among those who survive (p < 0.001), and the estimated change in average BCS per hour approaching death was -0.01 compared to 0.06 among the survivors (p < 0.001). Changes in temperature and heart rate were not associated with clinical deterioration. Three models were developed, and the best receiver operating characteristic curve was 100% sensitive, the corresponding false positive rate was 75%.

CONCLUSION: Changes in respiratory rate and BCS have prognostic significance in the final 24 hours before death in children with cerebral malaria. Extra attention should be paid to these two vital signs as they may help to identify children who are at increased risk of deteriorating.},
}

Humans
*Malaria, Cerebral/mortality/complications/diagnosis/physiopathology
Male
Female
Malawi/epidemiology
Retrospective Studies
Case-Control Studies
Child, Preschool
*Vital Signs
Infant
Child
*Malaria, Falciparum/mortality/complications
*Retinal Diseases/parasitology/mortality
Coma

@article {pmid40190112,
year = {2025},
author = {Moodie, Z and Li, SS and Giorgi, EE and Williams, LD and Dintwe, O and Carpp, LN and Chen, S and Seaton, KE and Sawant, SS and Zhang, L and Heptinstall, J and Liu, S and Grunenberg, N and Tomaka, F and Rerks-Ngarm, S and Pitisuttithum, P and Nitayaphan, S and Ake, JA and Vasan, S and Pantaleo, G and Frank, I and Baden, LR and Goepfert, PA and Keefer, M and Chirenje, M and Hosseinipour, MC and Mngadi, K and Laher, F and Garrett, N and Bekker, LG and De Rosa, S and Andersen-Nissen, E and Kublin, JG and Lu, S and Gilbert, PB and Gray, GE and Corey, L and McElrath, MJ and Tomaras, GD},
title = {A polyvalent DNA prime with matched polyvalent protein/GLA-SE boost regimen elicited the most robust and broad IgG and IgG3 V1V2 binding antibody and CD4+ T cell responses among 13 HIV vaccine trials.},
journal = {Emerging microbes & infections},
volume = {14},
number = {1},
pages = {2485317},
doi = {10.1080/22221751.2025.2485317},
pmid = {40190112},
issn = {2222-1751},
mesh = {Humans ; *AIDS Vaccines/immunology/administration & dosage ; *CD4-Positive T-Lymphocytes/immunology ; *HIV Infections/prevention & control/immunology/virology ; *HIV Antibodies/immunology/blood ; Female ; *Immunoglobulin G/immunology/blood ; Adult ; Male ; Vaccines, DNA/immunology/administration & dosage ; *HIV-1/immunology ; Young Adult ; Middle Aged ; Immunization, Secondary ; Immunogenicity, Vaccine ; Adolescent ; },
abstract = {Developing an effective HIV vaccine is a momentous challenge. An exceptionally wide range of candidate HIV vaccines have been tested, yet many were poorly immunogenic, and of the select few that advanced into efficacy trials, only one demonstrated any efficacy. Here we report the results of the largest-scale cross-protocol immunogenicity comparison to date: 13 HIV vaccine trials (including 36 vaccine regimens) conducted across nine countries worldwide, strengthened by standardized trial designs, validated assays in centralized laboratories, and harmonized immunogenicity endpoints - providing an objective approach to identify the HIV vaccine candidate(s) with the best immunogenicity. A polyvalent DNA prime + protein boost regimen (HVTN 124) including Env immunogens of four subtypes, matched between prime and boost, achieved the best anti-V1V2 antibody responses by a large margin and also induced high CD4+ T-cell responses - two key immune responses implicated in HIV vaccine protection. Our results provide strong support to test this promising HIV vaccine design in more advanced phase clinical trials and will also guide the future design of additional HIV vaccines.Trial registration: ClinicalTrials.gov identifier: NCT01799954..Trial registration: ClinicalTrials.gov identifier: NCT02109354..Trial registration: ClinicalTrials.gov identifier: NCT02404311..Trial registration: ClinicalTrials.gov identifier: NCT02207920..Trial registration: ClinicalTrials.gov identifier: NCT02296541..Trial registration: ClinicalTrials.gov identifier: NCT03284710..Trial registration: ClinicalTrials.gov identifier: NCT02915016..Trial registration: ClinicalTrials.gov identifier: NCT02997969..Trial registration: ClinicalTrials.gov identifier: NCT03122223..Trial registration: ClinicalTrials.gov identifier: NCT03409276..Trial registration: ClinicalTrials.gov identifier: NCT02968849..Trial registration: ClinicalTrials.gov identifier: NCT03060629..Trial registration: ClinicalTrials.gov identifier: NCT00223080..},
}

Humans
*AIDS Vaccines/immunology/administration & dosage
*CD4-Positive T-Lymphocytes/immunology
*HIV Infections/prevention & control/immunology/virology
*HIV Antibodies/immunology/blood
Female
*Immunoglobulin G/immunology/blood
Adult
Male
Vaccines, DNA/immunology/administration & dosage
*HIV-1/immunology
Young Adult
Middle Aged
Immunization, Secondary
Immunogenicity, Vaccine
Adolescent

@article {pmid40190065,
year = {2025},
author = {Osei-Assibey, BA and Lewis, FM},
title = {Helping Her Heal-Ghana: A pilot feasibility study of a culturally adapted educational counseling intervention for spouse caregivers of women with breast cancer.},
journal = {Palliative & supportive care},
volume = {23},
number = {},
pages = {e88},
doi = {10.1017/S1478951524002153},
pmid = {40190065},
issn = {1478-9523},
mesh = {Humans ; Female ; Ghana ; *Breast Neoplasms/psychology/complications/therapy ; Middle Aged ; Feasibility Studies ; Pilot Projects ; *Caregivers/psychology/education ; Adult ; *Counseling/methods/standards ; *Spouses/psychology ; Aged ; Male ; Adaptation, Psychological ; },
abstract = {INTRODUCTION: Breast cancer is the leading cancer in Ghana, Africa, accounting for 31% of all cancers in women. The effects of breast cancer are not limited to the woman but also impact the spouse's anxiety, depressed mood, and coping behavior. Helping Her Heal (HHH)-Ghana is a culturally adapted evidenced-based intervention with potential to improve health outcomes of spouse caregivers.

OBJECTIVES: The purpose of the study was to ascertain the feasibility, acceptability, and short-term impact of HHH-Ghana, a culturally adapted evidenced-based intervention for spouses of women with breast cancer in Ghana.

METHODS: The study used a single group pre-post design. Participants (n = 14) were recruited from medical care providers and were eligible if they were spouse caregivers of wives with Stage I, II, or III breast cancer, were 18 years or older, and had been living with their wives for at least 6 months. Data were obtained by spouse self-report on standardized measures of depressed mood, anxiety, self-care skills, self-efficacy to support their wife, self-efficacy to carry out their own self-care, and the quality of marital communication about breast cancer. Exit interviews were additionally obtained to describe the gains spouses attributed to their participation in the study.

RESULTS: The HHH-Ghana study was feasible and acceptable. Spouses actively engaged in each intervention session and completed the at-home assignments; retention was 87.5%. Spouses significantly improved on standardized measures of anxiety (p = 0.010), depressed mood (p = 0.002), self-care skills (p = 0.006), and their self-efficacy in supporting their wife (p = 0.001) and in carrying out their own self-care (p = 0.011). Although there was no statistically significant change in marital communication, spouses reported in their exit interviews that the intervention enabled them to communicate better and be more attentive listeners to their wives.

SIGNIFICANCE OF RESULTS: Results warrant a larger clinical trial in Ghana.},
}

Humans
Female
Ghana
*Breast Neoplasms/psychology/complications/therapy
Middle Aged
Feasibility Studies
Pilot Projects
*Caregivers/psychology/education
Adult
*Counseling/methods/standards
*Spouses/psychology
Aged
Male
Adaptation, Psychological

@article {pmid40188457,
year = {2025},
author = {Sarchi, M and Clough, CA and Gallì, A and Picone, C and Ferrari, B and Crosse, EI and Baquero Galvis, LD and Fiducioso, C and Aydinyan, N and Creamer, JP and Pozzi, S and Molteni, E and Elena, C and Bradley, RK and Malcovati, L and Doulatov, S},
title = {Distinct routes of clonal progression in SF3B1-mutant myelodysplastic syndromes.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2024014965},
pmid = {40188457},
issn = {2473-9537},
abstract = {Myelodysplastic syndromes (MDS) are clonal stem cell disorders driven by heterogeneous genetic alterations leading to variable clinical course. MDS with splicing factor SF3B1 mutations is a distinct subtype with a favorable outcome. However, selected co-mutations induce poor prognosis and how these genetic lesions cooperate in human hematopoietic stem and progenitor cells (HSPCs) during disease progression is still unclear. Here, we integrated clinical and molecular profiling of patients with SF3B1 mutations with gene editing of primary and iPSC-derived human HSPCs to show that high-risk co-mutations impart distinct effects on lineage programs of SF3B1-mutant HSPCs. Secondary RUNX1 or STAG2 mutations were clinically associated with advanced disease and reduced survival. However, RUNX1 and STAG2 mutations induced opposing regulation of myeloid transcriptional programs and differentiation in SF3B1-mutant HSPCs. Moreover, high-risk RUNX1 and STAG2, but not low-risk TET2, mutations expanded distinct SF3B1-mutant HSPC subpopulations. These findings provide evidence that progression from low- to high-risk MDS involves distinct molecular and cellular routes depending on co-mutation patterns.},
}

@article {pmid40187495,
year = {2025},
author = {Guo, M and Keane, EP and Baliousis, M and Gudenkauf, LM and Mate-Kole, MN and Boardman, AC and Larizza, IS and Song, MT and Wolfe, ED and Schaefer, DA and Cutler, C and Jim, HS and Lee, SJ and El-Jawahri, A and Amonoo, HL},
title = {A Structured Peer Support Intervention for Patients with Hematologic Malignancies Undergoing Hematopoietic Stem Cell Transplantation: Peer Support Interventionists' Perspectives.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.03.017},
pmid = {40187495},
issn = {2666-6367},
abstract = {BACKGROUND: Peer support is emerging as an important component of supportive care for patients with hematologic malignancies, but it has not been robustly implemented in patients undergoing hematopoietic stem cell transplantation (HSCT).

OBJECTIVES: This qualitative study aimed to explore the experiences of peer support interventionists (participants) delivering a structured, five-session, phone-delivered peer support intervention, the Supporting Transplant Experiences with Peer Program (STEPP) for patients undergoing HSCT.

METHODS: Adult patients who underwent allogeneic or autologous HSCT for the treatment of a hematologic malignancy within the past three years were eligible to volunteer in this study as trained STEPP participants. Semi-structured qualitative interviews were conducted to explore participants' experiences, including their motivations for volunteering, reflections on intervention delivery and on the impact of peer support, and challenges faced while serving in this role. Interviews were deductively analyzed by two coders using framework-guided rapid analysis.

RESULTS: Twenty STEPP interventionists participated in this study. Participants were 65% men, with a median age of 63.5 years. 75% had undergone allogeneic HSCT. Emerging themes from the qualitative interviews highlighted that participants were motivated to serve as interventionists by a sense of gratitude for their transplant care and a desire to share their transplant experiences with others. The impact of the STEPP intervention on interventionists included opportunities to process their transplant journey while also providing support to their peers. Interventionists reported a preference for free-flowing conversations, which were still guided by the structured manual. Challenges included terminating the interventionist-patient relationship at the conclusion of STEPP.

CONCLUSION: Peer support interventions for patients undergoing HSCT have the potential to enhance well-being and provide meaning for both patients preparing to undergo HSCT and HSCT survivors who serve as interventionists. Large-scale randomized clinical trials are needed to test the efficacy of peer support interventions for improving health-related outcomes among patients undergoing HSCT and HSCT survivors serving as interventionists for these interventions.},
}

@article {pmid40187050,
year = {2025},
author = {Rajan, A and Karpac, J},
title = {Inter-organ communication in Drosophila: Lipoproteins, adipokines, and immune-metabolic coordination.},
journal = {Current opinion in cell biology},
volume = {94},
number = {},
pages = {102508},
doi = {10.1016/j.ceb.2025.102508},
pmid = {40187050},
issn = {1879-0410},
abstract = {Inter-organ communication networks are essential for maintaining systemic homeostasis in multicellular organisms. In Drosophila melanogaster, studies of adipokines and lipoproteins reveal evolutionarily conserved mechanisms coordinating metabolism, immunity, and behavior. This mini-review focuses on two key pathways: the adipokine Unpaired 2 (Upd2) and lipoprotein-mediated signaling. Upd2, a leptin analog, mediates fat-brain communication to regulate insulin secretion, sleep, and feeding behavior. Recent work has uncovered an LC3/Atg8-dependent secretion mechanism for Upd2, linking nutrient sensing to systemic adaptation. Lipoproteins, particularly ApoLpp and LTP, function beyond lipid transport, orchestrating neural maintenance and immune responses. During infection, macrophage-derived signals trigger lipoprotein-mediated lipid redistribution to support host defense. Additionally, muscle tissue emerges as an unexpected mediator of immune-metabolic coordination through inter-organ signaling. These findings highlight the intricate cross-talk between organs required for organismal survival and suggest therapeutic strategies for metabolic disorders.},
}

@article {pmid40186724,
year = {2025},
author = {Hopkins, T and Bell-Brown, A and Martinez-Pinto, P and Henderson, V and Ko, LK and Isler, A and Issaka, RB},
title = {A Video Decision Aid Decreases Fear of Colonoscopy After an Abnormal Fecal Immunochemical Test Result: A Pilot Study.},
journal = {Journal of cancer education : the official journal of the American Association for Cancer Education},
volume = {},
number = {},
pages = {},
pmid = {40186724},
issn = {1543-0154},
support = {2022 Health Equity Research Award//American College of Gastroenterology/ ; K08CA241296/CA/NCI NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; },
abstract = {Colonoscopy completion after abnormal fecal immunochemical test (FIT) results is inadequate, and patient fear is a commonly reported barrier. We developed and piloted a video decision aid that addresses fear of colonoscopy among patients with abnormal FIT results. We developed a video decision aid and, in a pilot study, randomized patients in a safety-net healthcare system with abnormal FIT results and no follow-up colonoscopy to the intervention or usual care. Both groups completed a baseline survey that measured fear of colonoscopy, knowledge about colorectal cancer (CRC), self-efficacy, and intent to complete a colonoscopy, and the intervention group repeated the survey after watching the video. Sixty patients were enrolled in the study. Participants that watched the video reported a 17.7% decrease in fear of colonoscopy (p < 0.01) across six domains, including fear of the bowel prep (p < 0.01), the actual colonoscopy procedure (p < 0.01), and possible complications from the procedure (p = 0.04). Participant CRC knowledge also increased across several measures, including a 43.5% decrease in the belief that it is difficult to know which CRC prevention recommendations to follow. Overall, 78.3% of participants found the video to be helpful, and 90.6% would recommend the video to other patients with abnormal FIT results. In a safety-net population with abnormal FIT results, a video decision aid decreased fear of colonoscopy and increased knowledge about CRC. The video decision aid was acceptable to participants and can be considered an additional tool to improve follow-up of abnormal FIT results.},
}

@article {pmid40186355,
year = {2025},
author = {Choe, M and Einav, T and Phillips, R and Titov, DV},
title = {Glycolysis model shows that allostery maintains high ATP and limits accumulation of intermediates.},
journal = {Biophysical journal},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.bpj.2025.03.037},
pmid = {40186355},
issn = {1542-0086},
abstract = {Glycolysis is a conserved metabolic pathway that produces ATP and biosynthetic precursors. It is not well understood how the control of mammalian glycolytic enzymes through allosteric feedback and mass action accomplishes various tasks of ATP homeostasis, such as controlling the rate of ATP production, maintaining high and stable ATP levels, ensuring that ATP hydrolysis generates a net excess of energy, and maintaining glycolytic intermediate concentrations within physiological levels. To investigate these questions, we developed a biophysical model of glycolysis based on enzyme rate equations derived from in vitro kinetic data. This is the first biophysical model of human glycolysis that successfully recapitulates the above tasks of ATP homeostasis and predicts absolute concentrations of glycolytic intermediates and isotope tracing kinetics that align with experimental measurements in human cells. We use the model to show that mass action alone is sufficient to control the ATP production rate and maintain the high energy of ATP hydrolysis. Meanwhile, allosteric regulation of hexokinase (HK) and phosphofructokinase (PFK) by ATP, ADP, inorganic phosphate, and glucose-6-phosphate is required to maintain high ATP levels and to prevent uncontrolled accumulation of phosphorylated intermediates of glycolysis. Allosteric feedback achieves the latter by maintaining HK and PFK enzyme activity at one-half of ATP demand and, thus, inhibiting the reaction of Harden and Young, which otherwise converts glucose to supraphysiological levels of phosphorylated glycolytic intermediates at the expense of ATP. Our methodology provides a roadmap for a quantitative understanding of how metabolic homeostasis emerges from the activities of individual enzymes.},
}

@article {pmid40184567,
year = {2025},
author = {Menon, MP and Ddungu, H and Mubiru, KR and Adams, SV and Asea, J and Namagembe, R and Namuli, P and Kambugu, J and Towlerton, AMH and Puronen, C and Uldrick, TS and Orem, J and Warren, EH},
title = {Phase I Study of Subcutaneous Rituximab Hyaluronidase Combined With CHOP Chemotherapy for the Treatment of Diffuse Large B-Cell Lymphoma in Uganda.},
journal = {JCO global oncology},
volume = {11},
number = {},
pages = {e2400489},
doi = {10.1200/GO-24-00489},
pmid = {40184567},
issn = {2687-8941},
mesh = {Humans ; *Rituximab/administration & dosage/therapeutic use/pharmacology ; *Lymphoma, Large B-Cell, Diffuse/drug therapy/pathology/mortality ; Male ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/pharmacology/administration & dosage ; Female ; Adult ; Uganda ; Vincristine/therapeutic use/administration & dosage/pharmacology ; Cyclophosphamide/therapeutic use/administration & dosage/pharmacology ; Doxorubicin/therapeutic use/administration & dosage ; Prednisone/therapeutic use/administration & dosage/pharmacology ; Middle Aged ; *Hyaluronoglucosaminidase/administration & dosage/therapeutic use ; Young Adult ; },
abstract = {PURPOSE: Patients with diffuse large B-cell lymphoma (DLBCL) who are treated in low-resource settings have inferior outcomes compared with those in high-resource settings. Rituximab, an anti-CD20 monoclonal antibody, when combined with chemotherapy, improves overall survival (OS) for DLBCL. However, in part due to the limited availability of infusion centers in low-resource countries, rituximab is rarely used. Subcutaneous rituximab (sqR) is a potential solution; however, its safety and efficacy have not been tested in low-income countries.

METHODS: This open-label phase I study enrolled patients 18 years or older with newly diagnosed DLBCL. The first cohort (n = 6) received intravenous rituximab plus CHOP. This cohort received sqR for subsequent cycles. The second cohort (n = 12) received sqR plus CHOP for all cycles. Safety and tolerability were evaluated; secondary outcomes included response rates and treatment completion.

RESULTS: Between October 25, 2019, and October 7, 2022, 18 patients, with a median age of 36.5 years, were enrolled; 10 were male, and 10 presented with advanced-stage disease. The most common hematologic toxicity was neutropenia (n = 9, 50%). Fifteen of the 18 participants completed treatment; 14 (93.3%) patients achieved a complete response, and one patient (6.7%) had a partial response. The OS and progression-free survival (PFS) at 12 months were 83% (95% CI, 68 to 100) and 67% (95% CI, 48 to 92), respectively. The OS and PFS at 24 months were 66% (95% CI, 47 to 92) and 67% (95% CI, 48 to 92), respectively.

CONCLUSION: As demonstrated in other parts of the world, sqR together with CHOP was safe, well-tolerated, and efficacious among Ugandan patients with DLBCL. The very high OS rates are nearly double those of historical controls and comparable with outcomes expected in resource-rich settings. This study demonstrated the feasibility, safety, and efficacy of sqR-CHOP, increased the research infrastructure in Uganda, and will improve care in other resource-limited settings.},
}

Humans
*Rituximab/administration & dosage/therapeutic use/pharmacology
*Lymphoma, Large B-Cell, Diffuse/drug therapy/pathology/mortality
Male
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use/pharmacology/administration & dosage
Female
Adult
Uganda
Vincristine/therapeutic use/administration & dosage/pharmacology
Cyclophosphamide/therapeutic use/administration & dosage/pharmacology
Doxorubicin/therapeutic use/administration & dosage
Prednisone/therapeutic use/administration & dosage/pharmacology
Middle Aged
*Hyaluronoglucosaminidase/administration & dosage/therapeutic use
Young Adult

@article {pmid40184428,
year = {2025},
author = {Reeves, DB and Litchford, M and Fish, CS and Farrell-Sherman, A and Poindexter, M and Ahmed, N and Cassidy, NAJ and Neary, J and Wamalwa, D and Langat, A and Chebet, D and Moraa, H and Antar, AAR and Slyker, J and Benki-Nugent, S and Cohn, LB and Schiffer, JT and Overbaugh, J and John-Stewart, G and Lehman, DA},
title = {Intact HIV DNA decays in children with and without complete viral load suppression.},
journal = {PLoS pathogens},
volume = {21},
number = {4},
pages = {e1013003},
doi = {10.1371/journal.ppat.1013003},
pmid = {40184428},
issn = {1553-7374},
abstract = {To inform cure in children living with HIV (CWH), we elucidated the dynamics and mechanisms underlying HIV persistence during antiretroviral therapy (ART). In 120 Kenyan CWH who initiated ART between 1-12 months of age, 55 had durable viral load suppression, and 65 experienced ART interruptions. We measured plasma HIV RNA levels, CD4+ T cell count, and levels of intact and defective HIV DNA proviruses via the cross-subtype intact proviral DNA assay (CS-IPDA). By modeling data from the durably suppressed subset, we found that during early ART (year 0-1 on ART), plasma RNA levels decayed rapidly and biphasically and intact and defective HIV DNA decayed with mean 3 and 9 month half-lives, respectively. After viral suppression was achieved (years 1-8 on ART), intact HIV DNA decay slowed to a mean 22 month half-life, whilst defective HIV DNA no longer decayed. In five CWH, we found individual CD4+ TCRβ clones wax and wane, but average kinetics resembled those of defective DNA and CD4 count, suggesting that differential decay of intact HIV DNA arises from selective pressures overlaying normal CD4+ T cell kinetics. Finally, by modeling HIV RNA and DNA in CWH with treatment interruptions, we linked temporary viremia to transient rises in HIV DNA, but long-term intact reservoirs were not strongly influenced, suggesting brief treatment interruptions may not significantly increase HIV reservoirs in children.},
}

@article {pmid40184422,
year = {2025},
author = {Nelson, CR and Mallett, DR and Biggins, S},
title = {Spindle integrity is regulated by a phospho-dependent interaction between the Ndc80 and Dam1 kinetochore complexes.},
journal = {PLoS genetics},
volume = {21},
number = {4},
pages = {e1011645},
doi = {10.1371/journal.pgen.1011645},
pmid = {40184422},
issn = {1553-7404},
abstract = {Faithful chromosome segregation depends upon kinetochores, large protein complexes that anchor chromosomes to dynamic microtubules, allowing for their movement at anaphase. Critical microtubule-coupling components of the budding yeast kinetochore, the Dam1 (Dam1c) and Ndc80 (Ndc80c) complexes, work cooperatively to ensure that kinetochores track with the plus-ends of microtubules. Additionally, the Dam1 complex plays a distinct role in ensuring the integrity of the mitotic spindle. However, the events required to orchestrate these diverse functions of Dam1c remain unclear. To identify regulatory events on kinetochores, we performed phosphoproteomics on purified kinetochore proteins and identified many previously unknown phosphorylation events. We demonstrate that Ndc80 is phosphorylated at Thr-248 and Thr-252 to promote the interaction between Ndc80 and the Dam1c. The phosphorylation of T248 is cell cycle regulated and depends on Mps1. Ndc80 phosphorylation at T248 and T252 does not appear to regulate kinetochore function and instead contributes to Dam1c localization to the anaphase spindle. A ndc80 phospho-deficient mutant exhibited a genetic interaction and altered spindle morphology when combined with dam1 mutant alleles. Taken together, we propose that Mps1-dependent phosphorylation of Ndc80 at T248 and T252 is removed at anaphase to allow Dam1c to help organize and stabilize the spindle.},
}

@article {pmid40180499,
year = {2025},
author = {Porter, J and Ward, LC and Nguo, K and Davidson, Z and Gibson, S and Prentice, R and Neuhouser, ML and Truby, H},
title = {Investigating the impact of body composition on the estimation of resting metabolic rate: new equations for adults aged ≥65 years developed using cross-sectional data.},
journal = {The American journal of clinical nutrition},
volume = {121},
number = {4},
pages = {795-803},
doi = {10.1016/j.ajcnut.2024.12.023},
pmid = {40180499},
issn = {1938-3207},
mesh = {Humans ; *Basal Metabolism ; *Body Composition ; Aged ; Male ; Female ; Cross-Sectional Studies ; Aged, 80 and over ; },
abstract = {BACKGROUND: Due to changes in body composition during aging, the inclusion of body composition measures as a variable within equations to predict resting metabolic rate (RMR) may improve their predictive accuracy.

OBJECTIVES: This analysis of cross-sectional data aimed to develop and validate new RMR equations for older adults (≥65 y) incorporating variables for body composition, to predict performance and accuracy, and to explore the relative contribution of body composition variables acting directly or potentially via fat-free mass (FFM) to RMR.

METHODS: Analyses were conducted utilizing a unique international dataset of gold standard measures developed for this purpose. RMR was predicted from potential predictive variables using stepwise multiple regression. Predictive performance of the final model was assessed using double cross-validation. The new prediction equation was compared with published prediction equations for similar populations and with previously published RMR prediction equations that did not include FFM. Direct associations between the determined predictor variables and RMR with indirect effects mediated via FFM were examined using mediation final (or pathway) analysis.

RESULTS: The dataset contained 1238 participants. The predictive equations {utilizing either FFM (Equation 1) or lean body weight [LBW](Equation 2)}
follow. Equation 1: RMR = 8.645 × height + 23.684 × weight - 29.717 × age + 38.213 × FFM + 209.637 × sex + 2693.223; Equation 2: RMR = -30.570 × age + 80.736 × LBW - 186.825 × sex + 3956.822 where RMR (kJ/d); height (cm); weight (kg); age (y); FFM (kg); LBW (kg); sex (M = 1, F = 0). The equation performed similarly to some anthropometric-based prediction equations. Predictors using FFM performed marginally better than those using LBW. All variables had significant (P < 0.001) direct effects upon RMR and significant (P < 0.001) indirect effects for sex, weight, and height.

CONCLUSIONS: New prediction equations predict RMR at the population level with minimal bias; however, the difference in performance with anthropometry-based equations is minimal. This may be explained by the contribution of FFM to weight, whereby equations that include weight are already accounting for FFM.},
}

Humans
*Basal Metabolism
*Body Composition
Aged
Male
Female
Cross-Sectional Studies
Aged, 80 and over

@article {pmid40180419,
year = {2025},
author = {Arias-Badia, M and Pai, CS and Lwin, YM and Chen, P and Srinath, A and Tanaka, M and Musser, E and Goodearl, A and Gorman, JV and Ritacco, W and Fong, L},
title = {Impact of tumor localization on antitumor immunity with conditionally activated CTLA-4 blockade.},
journal = {Journal for immunotherapy of cancer},
volume = {13},
number = {4},
pages = {},
pmid = {40180419},
issn = {2051-1426},
support = {P30 DK063720/DK/NIDDK NIH HHS/United States ; R35 CA253175/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; Mice ; *CTLA-4 Antigen/antagonists & inhibitors ; Humans ; *Immune Checkpoint Inhibitors/pharmacology/therapeutic use ; Male ; Cell Line, Tumor ; *Neoplasms/immunology/drug therapy ; *Immunotherapy/methods ; },
abstract = {BACKGROUND: Immune checkpoint blockade (ICB) can induce antitumor efficacy but also induces immune-related adverse events. Systemically administered ICB can activate immune cells throughout the host. Conditionally active ICB with proteolytically cleaved masking domains can potentially reduce the adverse events seen with anti-cytotoxic T-lymphocyte associated protein 4 (CTLA-4) antibody.

METHODS: We examined how different formats of a conditionally activated dual variable domain IgG (DVD) that binds CTLA-4 and the tumor-associated antigen prostate stem cell antigen (PSCA) can lead to efficacy in syngeneic subcutaneous and metastatic murine tumor models. We also defined the capacity of these DVDs to modulate immune responses by multiparameter flow cytometry.

RESULTS: Conditionally active DVDs can uncouple antitumor efficacy from toxicity. A fully cleavable construct (symmetric DVD, sDVD), which can be released from the target tumor cells, showed superior antitumor efficacy compared with asymmetric DVD, which retains its tumor antigen binding. The sDVD elicited the highest tumor-antigen-specific T-cell responses detected in tumors and tumor-draining lymph nodes, as well as presenting the highest rate of intratumoral and splenic "non-exhausted" antigen-specific CD8 T cells. SDVD also induced the highest degrees of T-cell memory and self-renewal potential. These effects were dependent on PSCA expression by the tumors.

CONCLUSIONS: These findings support the notion that ICB modulation of antitumor immunity away from the tumor cells is critically important for optimal antitumor immunity. The bispecific sDVD antibody design may enable improved systemic antitumor responses than traditional ICB in both primary tumors and metastases.},
}

Animals
Mice
*CTLA-4 Antigen/antagonists & inhibitors
Humans
*Immune Checkpoint Inhibitors/pharmacology/therapeutic use
Male
Cell Line, Tumor
*Neoplasms/immunology/drug therapy
*Immunotherapy/methods

@article {pmid40180180,
year = {2025},
author = {Diacova, T and Cifelli, CJ and Davis, CD and Holscher, HD and Kable, ME and Lampe, JW and Latulippe, ME and Swanson, KS and Karl, JP},
title = {Best Practices and Considerations for Conducting Research on Diet-Gut Microbiome Interactions and their Impact on Health in Adult Populations: An Umbrella Review.},
journal = {Advances in nutrition (Bethesda, Md.)},
volume = {},
number = {},
pages = {100419},
doi = {10.1016/j.advnut.2025.100419},
pmid = {40180180},
issn = {2156-5376},
abstract = {Diet modulates gut microbiome composition and function. However, determining causal links between diet-gut microbiome interactions and human health is complicated by inconsistencies in the evidence, arising partially from variability in research methods and reporting. Widespread adoption of standardized best practices would advance the field but requires those practices be identified, consolidated and discussed. This umbrella review aimed to identify recommended best practices, define existing gaps, and collate considerations for conducting research on diet-gut microbiome interactions and their impact on human health outcomes. Reviews meeting inclusion criteria and published after 2013 were identified using a systematic search. Recommendations, considerations and gaps relating to best practices associated with study design, participant selection, dietary intervention/assessment, biological sample collection, and data analysis and reporting were extracted and consolidated. Eight narrative reviews were included. Several general points of agreement were identified, and a recurring theme was that best practices are dependent upon the research aims, outcomes and feasibility. Multiple gaps were also identified. Some, such as suboptimal diet assessment methods and lack of validated dietary intake biomarkers, are particularly relevant to nutrition science. Others, including defining a "healthy" gut microbiome and the absence of standardized sample and data collection/analysis protocols were relevant specifically to gut microbiome research. Gaps specific to diet-gut microbiome research include the underrepresentation of microbiome-modulating dietary components in food databases, lack of knowledge regarding interventions eliciting changes in the gut microbiome to confer health benefits, lack of in situ measurement methods and the need to further develop and refine statistical approaches for integrating diet and gut microbiome data. Future research and cross-disciplinary exchange will address these gaps and evolve best practices. In the interim, the best practices and considerations discussed herein, and the publications from which that information was extracted, provide a roadmap for conducting diet-gut microbiome research. PROSPERO registration: CRD42023437645.},
}

@article {pmid40179338,
year = {2025},
author = {Wu, M and Russell, K and Shaw, CM and Halpern, AB and Ghiuzeli, C and Appelbaum, JS and Hendrie, P and Walter, RB and Percival, MM},
title = {Predictors of Cardiac Recovery in Adults With AML Who Develop Heart Failure During Treatment.},
journal = {JCO oncology practice},
volume = {},
number = {},
pages = {OP2400734},
doi = {10.1200/OP-24-00734},
pmid = {40179338},
issn = {2688-1535},
abstract = {PURPOSE: Heart failure is a leading cause of death in patients with AML, who face higher risks of cardiac complications than nonleukemic cancer patients treated with anthracyclines. This study examines factors associated with myocardial dysfunction and recovery occurring during treatment of AML.

METHODS: We retrospectively analyzed patients with AML who sustained reduced left ventricular ejection fraction (LVEF) during induction therapy at the University of Washington/Fred Hutchinson Cancer Center (2008-2022). Multivariable analysis compared characteristics between patients who eventually recovered LVEF and those who did not, with survival analysis performed by landmark censoring.

RESULTS: Of 86 patients with AML diagnosed with systolic dysfunction, 41 (48%) failed to recover LVEF. These patients were more frequently male, older than 60 years, had preexisting cardiovascular risk factors, and leukemias of higher risk. Ischemia-related systolic failure was associated with nonrecovery (B = -2.89, P = .005), whereas chemotherapy-related dysfunction was associated with eventual recovery (B = 1.15, P = .014). Frequent use and higher doses of guideline-directed medical therapy (GDMT) were found among patients who recovered LVEF. Failure to recover cardiac function was associated with a greater incidence of cardiac-specific mortality (51% v 23%, P = .042), although impact on overall survival was unclear.

CONCLUSION: Our retrospective single-center analysis suggests that approximately half of the patients with AML who experience LVEF decline during induction will not recover. Ischemic events during treatment were predictive of nonrecovery. The use of GDMT may improve prognosis for some patients. Given the impact of recovery, we propose the prospective verification and establishment of cardiac management algorithms in patients with AML.},
}

@article {pmid40178906,
year = {2025},
author = {Violari, A and Otwombe, K and Hahn, W and Chen, S and Josipovic, D and Baba, V and Angelidou, A and Smolen, KK and Levy, O and Mkhize, NN and Woodward Davis, AS and Martin, TM and Haynes, BF and Williams, WB and Sagawa, ZK and Kublin, JG and Polakowski, L and Brewinski Isaacs, M and Yen, C and Tomaras, G and Corey, L and Janes, H and Gray, GE},
title = {Safety and implementation of phase 1 randomized GLA-SE-adjuvanted CH505TF gp120 HIV vaccine trial in newborns.},
journal = {The Journal of clinical investigation},
volume = {},
number = {},
pages = {},
doi = {10.1172/JCI186927},
pmid = {40178906},
issn = {1558-8238},
abstract = {BACKGROUND: The neonatal immune system is uniquely poised to generate broadly neutralizing antibodies (bnAbs) and thus infants are ideal for evaluating HIV vaccine candidates. We present the design and safety of a new-in-infants glucopyranosyl lipid A (GLA)-stable emulsion (SE) adjuvant admixed with a first-in-infant CH505 transmitter-founder (CH505TF) gp120 immunogen designed to induce precursors for bnAbs against HIV.

METHODS: HVTN 135 is a phase I randomized, placebo-controlled trial of CH505TF+GLA-SE or placebo. Healthy infants aged ≤ 5 days, born to mothers living with HIV but HIV nucleic acid negative at birth were randomized to five doses of CH505TF + GLA-SE or placebo at birth and 8, 16, 32, and 54 weeks.

RESULTS: 38 infants (median age = 4 days; interquartile range 4, 4.75 days) were enrolled November 2020 to January 2022. Among 28 (10) infants assigned to receive CH505TF + GLA-SE (placebo), most (32/38) completed the 5-dose immunization series and follow-up (35/38). Solicited local and systemic reactions were more frequent in vaccine (8, 28.6% local; 16, 57.1% systemic) vs. placebo recipients (1, 10% local, P = 0.25; 4, 40.0% systemic, P = 0.38). All events were Grade 1 except two Grade 2 events (pain, lethargy). Serious vaccine-related adverse events were not recorded.

CONCLUSIONS: This study illustrates the feasibility of conducting trials of new-in-infants adjuvanted HIV vaccines in HIV-exposed infants receiving standard infant vaccinations. The safety profile of the CH505TF + GLA-SE vaccine was reassuring.

CLINICALTRIALS: gov NCT04607408.

FUNDING: The trial was funded through National Institute of Allergy and Infectious Disease of the National Institutes of Health under grants UM1 AI068614 (HVTN Leadership and Operations Center), UM1 AI068635 (HVTN Statistical and Data Management Center), and UM1 AI068618 (HVTN Laboratory Center).},
}

@article {pmid40176173,
year = {2025},
author = {Hu, Y and Haessler, J and Lundin, JI and Darst, BF and Whitsel, EA and Grove, M and Guan, W and Xia, R and Szeto, M and Raffield, LM and Ratliff, S and Wang, Y and Wang, X and Fohner, AE and Lynch, MT and Patel, YM and Lani Park, S and Xu, H and Mitchell, BD and Bis, JC and Sotoodehnia, N and Brody, JA and Psaty, BM and Peloso, GM and Tsai, MY and Rich, SS and Rotter, JI and Smith, JA and Kardia, SLR and Reiner, AP and Lange, L and Fornage, M and Pankow, JS and Graff, M and North, KE and Kooperberg, C and Peters, U},
title = {Methylome-wide association analyses of lipids and modifying effects of behavioral factors in diverse race and ethnicity participants.},
journal = {Clinical epigenetics},
volume = {17},
number = {1},
pages = {54},
pmid = {40176173},
issn = {1868-7083},
support = {N01HC95160/HL/NHLBI NIH HHS/United States ; 75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, 75N92021D00005, and S10OD028685/NH/NIH HHS/United States ; 75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, UL1-TR-000040, UL1-TR-001079, UL1-TR-001420, UL1TR001881, DK063491, HL148610, and R01HL105756/HL/NHLBI NIH HHS/United States ; R01 HL087652/HL/NHLBI NIH HHS/United States ; UL1 TR000040/TR/NCATS NIH HHS/United States ; HHSN268201800010I/HB/NHLBI NIH HHS/United States ; N01HC85081/HL/NHLBI NIH HHS/United States ; R01 HL103612/HL/NHLBI NIH HHS/United States ; 75N92020D00002/HL/NHLBI NIH HHS/United States ; 75N92021D00002/HL/NHLBI NIH HHS/United States ; HHSN268201500003C/HL/NHLBI NIH HHS/United States ; U01HG007397/HG/NHGRI NIH HHS/United States ; HHSN268201800012C/HL/NHLBI NIH HHS/United States ; 75N92020D00005/HL/NHLBI NIH HHS/United States ; 75N92021D00005/WH/WHI NIH HHS/United States ; U01HL054457, RC1HL100185, R01HL087660, R01HL119443, R01HL133221/HL/NHLBI NIH HHS/United States ; 75N92022D00001/NH/NIH HHS/United States ; N01HC95163/HL/NHLBI NIH HHS/United States ; U01 HL080295/HL/NHLBI NIH HHS/United States ; UL1 TR001079/TR/NCATS NIH HHS/United States ; DK063491//National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center/ ; HHSN268201800014I/HB/NHLBI NIH HHS/United States ; U01CA164973/CA/NCI NIH HHS/United States ; U01 HL130114/HL/NHLBI NIH HHS/United States ; R01 HL087660/HL/NHLBI NIH HHS/United States ; HHSN268200800007C/HL/NHLBI NIH HHS/United States ; S10 OD028685/OD/NIH HHS/United States ; 75N92020D00001/HL/NHLBI NIH HHS/United States ; N01HC95169/HL/NHLBI NIH HHS/United States ; N01HC95164/HL/NHLBI NIH HHS/United States ; UL1 TR000124/TR/NCATS NIH HHS/United States ; N01HC55222/HL/NHLBI NIH HHS/United States ; HHSN268201800014C/HL/NHLBI NIH HHS/United States ; N01HC95162/HL/NHLBI NIH HHS/United States ; N01HC85086/HL/NHLBI NIH HHS/United States ; 75N92020D00003/HL/NHLBI NIH HHS/United States ; R01 HL119443/HL/NHLBI NIH HHS/United States ; R01 HL105756/HL/NHLBI NIH HHS/United States ; N01HC95168/HL/NHLBI NIH HHS/United States ; K08 HL116640/HL/NHLBI NIH HHS/United States ; 75N92021D00001/HL/NHLBI NIH HHS/United States ; P30 DK063491/DK/NIDDK NIH HHS/United States ; RC1 HL100185/HL/NHLBI NIH HHS/United States ; HHSN268201200036C/HL/NHLBI NIH HHS/United States ; HHSN268201800001C/HL/NHLBI NIH HHS/United States ; HHSN268201800013I/MD/NIMHD NIH HHS/United States ; UL1TR000124/TR/NCATS NIH HHS/United States ; U01 HL054457/HL/NHLBI NIH HHS/United States ; N01HC95165/HL/NHLBI NIH HHS/United States ; N01HC95159/HL/NHLBI NIH HHS/United States ; HHSN268201800012I/HL/NHLBI NIH HHS/United States ; 75N92021D00003/WH/WHI NIH HHS/United States ; N01HC95161/HL/NHLBI NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; 75N92020D00004/HL/NHLBI NIH HHS/United States ; HHSN268201800011C/HL/NHLBI NIH HHS/United States ; 75N92020D00007/HL/NHLBI NIH HHS/United States ; R01AG023629/AG/NIA NIH HHS/United States ; HHSN268201800013I, HHSN268201800014I, HHSN268201800015I, HHSN268201800010I, HHSN268201800011I, and HHSN268201800012I/MD/NIMHD NIH HHS/United States ; HHSN268201500003I/HL/NHLBI NIH HHS/United States ; R01HL105756, HHSN268201200036C, HHSN268200800007C, HHSN268201800001C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, R01AG023629, 75N92021D00006, U01HL080295, U01HL130114, K08HL116640, R01HL087652, R01HL092111, R01HL103612, R01HL111089, R01HL116747 and R01HL120393/HL/NHLBI NIH HHS/United States ; R01 HL133221/HL/NHLBI NIH HHS/United States ; 75N92021D00006/HL/NHLBI NIH HHS/United States ; R01HG010297/HG/NHGRI NIH HHS/United States ; N01HC85082/HL/NHLBI NIH HHS/United States ; N01HC95167/HL/NHLBI NIH HHS/United States ; N01HC85083/HL/NHLBI NIH HHS/United States ; HHSN268201800015I/HB/NHLBI NIH HHS/United States ; 75N92020D00006/HL/NHLBI NIH HHS/United States ; N01HC85079/HL/NHLBI NIH HHS/United States ; N01HC95166/HL/NHLBI NIH HHS/United States ; R01 AG023629/AG/NIA NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; HHSN268201800011I/HB/NHLBI NIH HHS/United States ; N01HC85080/HL/NHLBI NIH HHS/United States ; R01 HG010297/HG/NHGRI NIH HHS/United States ; U01 CA164973/CA/NCI NIH HHS/United States ; 75N92021D00004/WH/WHI NIH HHS/United States ; R01 HL111089/HL/NHLBI NIH HHS/United States ; R01 HL116747/HL/NHLBI NIH HHS/United States ; R01 HL092111/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *Genome-Wide Association Study/methods ; Female ; Male ; *DNA Methylation/genetics ; Middle Aged ; CpG Islands ; Adult ; Alcohol Drinking/genetics ; *Lipids/blood/genetics ; Ethnicity/genetics ; Racial Groups/genetics ; Smoking/genetics ; White People/genetics ; Aged ; },
abstract = {Circulating lipid concentrations are clinically associated with cardiometabolic diseases. The phenotypic variance explained by identified genetic variants remains limited, highlighting the importance of searching for additional factors beyond genetic sequence variants. DNA methylation has been linked to lipid concentrations in previous studies, although most of the studies harbored moderate sample sizes and exhibited underrepresentation of non-European ancestry populations. In addition, knowledge of nongenetic factors on lipid profiles is extremely limited. In the Population Architecture Using Genomics and Epidemiology (PAGE) Study, we performed methylome-wide association analysis on 9,561 participants from diverse race and ethnicity backgrounds for HDL-c, LDL-c, TC, and TG levels, and also tested interactions between smoking or alcohol intake and methylation in their association with lipid levels. We identified novel CpG sites at 16 loci (P < 1.18E-7) with successful replication on 3,215 participants. One additional novel locus was identified in the self-reported White participants (P = 4.66E-8). Although no additional CpG sites were identified in the genome-wide interaction analysis, 13 reported CpG sites showed significant heterogeneous association across smoking or alcohol intake strata. By mapping novel and reported CpG sites to genes, we identified enriched pathways directly linked to lipid metabolism as well as ones spanning various biological functions. These findings provide new insights into the regulation of lipid concentrations.},
}

Humans
*Genome-Wide Association Study/methods
Female
Male
*DNA Methylation/genetics
Middle Aged
CpG Islands
Adult
Alcohol Drinking/genetics
*Lipids/blood/genetics
Ethnicity/genetics
Racial Groups/genetics
Smoking/genetics
White People/genetics
Aged

@article {pmid40014402,
year = {2025},
author = {Arias-Badia, M and Chen, P and Lwin, YM and Srinath, A and Lyu, A and Fan, Z and Kwek, SS and Luong, DN and Setayesh, A and Sakamoto, M and Clark, M and Lea, A and Wolters, RM and Goodearl, A and Harding, FA and Gorman, JV and Ritacco, W and Fong, L},
title = {Sequential JAK inhibition enhances antitumor immunity after combined anti-PD-1 and anti-CTLA4.},
journal = {JCI insight},
volume = {10},
number = {7},
pages = {},
doi = {10.1172/jci.insight.187921},
pmid = {40014402},
issn = {2379-3708},
mesh = {Animals ; Interferon-gamma/metabolism/immunology ; Female ; Humans ; Mice, Inbred C57BL ; Imidazoles/pharmacology ; },
abstract = {While immune checkpoint inhibition (CPI) has reshaped cancer treatment, the majority of patients with cancer do not benefit from this approach, which can also cause immune-related adverse events. Induction of IFN-γ responses is thought be necessary for antitumor immunity, but growing evidence also implicates IFN-γ as a tumor-intrinsic mediator of CPI resistance. CPI-induced IFN-γ mediates activation-induced cell death in T cells as an immune-intrinsic mechanism of resistance. In this study, we found that transient block of IFN-γ signaling through administration of the JAK1 inhibitor ABT-317 enhanced antitumor T cell responses with CPI in preclinical models. Importantly, sequential but not concomitant ABT-317 treatment led to significantly reduced toxicity and improved tumor efficacy. Sequential treatment reduced activation-induced T cell death and enhanced expansion of tumor-reactive T cell subsets with increased effector function in vivo and ex vivo. Only CPI in combination with ABT-317 also enhanced memory responses by protecting mice from tumor rechallenge. These results demonstrate that JAK inhibition within a discrete time window following CPI addresses an immune-intrinsic mechanism of therapeutic resistance.},
}

Animals
Interferon-gamma/metabolism/immunology
Female
Humans
Mice, Inbred C57BL
Imidazoles/pharmacology

@article {pmid40175263,
year = {2025},
author = {Chari, A and Bal, S and Ailawadhi, S and Krishnan, A and Patel, KK and Berdeja, JG and Garfall, A and Callander, N and Banerjee, R and Alsina, M and Nooka, AK and Dhakal, B and Gasparetto, C and Costello, C},
title = {Expert Perspectives on Current Challenges and Emerging Approaches for Multiple Myeloma: Narrative Review of an Inaugural Bridging the Gaps in Leukemia, Lymphoma, and Multiple Myeloma.},
journal = {Clinical lymphoma, myeloma & leukemia},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.clml.2025.03.008},
pmid = {40175263},
issn = {2152-2669},
abstract = {PURPOSE: The management of multiple myeloma (MM) is becoming increasingly more complex. The approval of novel treatment approaches provides much-needed opportunities but also raises questions and controversies about how to optimally sequence therapies and select treatments for individual patients.

METHODS AND RESULTS: A panel of experts assembled to discuss current controversies in the care of patients with MM across the disease continuum. Workshop topics included: management of smoldering MM; treatment selection for transplant-eligible and transplant-ineligible patients; risk assessment and the possibility of risk-adapted treatment; use of measurable residual disease (MRD) as a clinical trial end point and to guide treatment decisions; management of early relapse; management of triple class-refractory MM; treatment sequencing; and novel therapies.

CONCLUSION: Many controversies remain regarding the management of patients with MM related to risk assessment, treatment selection and sequencing, and the optimal use of current therapies while balancing efficacy, toxicity, patient considerations, and treatment logistics. Ongoing research efforts are needed to further define the optimal use of current therapies and to develop more efficacious therapies for all patients and for particular subset populations with unmet need.},
}

@article {pmid40173015,
year = {2025},
author = {Russell, ML and Trofimov, A and Bradley, P and Matsen Iv, FA},
title = {Statistical analysis of repertoire data demonstrates the influence of microhomology in V(D)J recombination.},
journal = {Nucleic acids research},
volume = {53},
number = {6},
pages = {},
pmid = {40173015},
issn = {1362-4962},
support = {R01 AI146028/GF/NIH HHS/United States ; //Mahan Fellowship/ ; /HHMI/Howard Hughes Medical Institute/United States ; },
mesh = {*V(D)J Recombination/genetics ; Humans ; High-Throughput Nucleotide Sequencing ; Receptors, Antigen, T-Cell, alpha-beta/genetics ; Animals ; },
abstract = {V(D)J recombination generates the diverse B and T cell receptors essential for recognizing a wide array of antigens. This diversity arises from the combinatorial assembly of V(D)J genes and the junctional deletion and insertion of nucleotides. While previous in vitro studies have shown that microhomology-short stretches of sequence homology between gene ends-can bias the recombination process, the extent of microhomology's impact in vivo, particularly in humans, remains unknown. In this paper, we assess how germline-encoded microhomology influences trimming and ligation during V(D)J recombination using statistical inference on previously published high-throughput TCRα repertoire sequencing data. We find that microhomology increases both trimming and ligation probabilities, making it an important predictor of recombination outcomes. These effects are consistent across other receptor loci and sequence types. Further, we demonstrate that accounting for germline microhomology effects significantly alters sequence annotation probabilities and rankings, highlighting its practical importance for accurately inferring the V(D)J recombination events that generated an observed sequence. Together, these results enhance our understanding of how germline-encoded microhomologous nucleotides shape the human V(D)J recombination process.},
}

*V(D)J Recombination/genetics
Humans
High-Throughput Nucleotide Sequencing
Receptors, Antigen, T-Cell, alpha-beta/genetics
Animals

@article {pmid40172323,
year = {2025},
author = {Milch, HS and Lee, CI},
title = {Establishing the Evidence Needed for AI-driven Mammography Screening.},
journal = {Radiology. Artificial intelligence},
volume = {7},
number = {3},
pages = {e250152},
doi = {10.1148/ryai.250152},
pmid = {40172323},
issn = {2638-6100},
}

@article {pmid40171709,
year = {2025},
author = {Nakamura, M and Parkhurst, SM},
title = {Septin complexes: Ahead of the curve.},
journal = {Cytoskeleton (Hoboken, N.J.)},
volume = {82},
number = {4},
pages = {229-233},
pmid = {40171709},
issn = {1949-3592},
support = {R01 GM111635/GM/NIGMS NIH HHS/United States ; },
mesh = {*Septins/metabolism ; Animals ; Actomyosin/metabolism ; Actin Cytoskeleton/metabolism ; Drosophila Proteins/metabolism ; Actins/metabolism ; Drosophila/metabolism ; },
abstract = {Individual cells have robust repair systems to survive cell cortex damage caused by mechanical and chemical stresses, allowing them to maintain the integrity of tissues and organs. The contraction of an actomyosin ring at the wound edge is a major mechanism for physically closing the cell wound. In contrast to polymerization and bundling of actin filaments, little is known about how linear actin filaments are bent to be integrated into the actin ring structure encircling the wound edge. We recently found that the five Drosophila Septins function simultaneously in the regulation of actomyosin ring assembly, contraction, and disassembly during cell wound repair. These Septins form two distinct complexes-Sep1-Sep2-Pnut and Sep4-Sep5-Pnut-composed of different subunits from the same groups. Strikingly, these two distinct Septin complexes have different degrees of F-actin bending activities that are consistent with their spatial recruitment: different degrees of curved actin filaments are required for the robust formation of different regions of the actomyosin ring. In addition, we found that the two Septin complexes are regulated by different molecular pathways as a loss of Anillin only affects Sep1-Sep2-Pnut complex recruitment. These findings open new directions for how individual Septin subunits form complexes and function differentially in cellular and developmental processes.},
}

*Septins/metabolism
Animals
Actomyosin/metabolism
Actin Cytoskeleton/metabolism
Drosophila Proteins/metabolism
Actins/metabolism
Drosophila/metabolism