@article {pmid40016020,
year = {2025},
author = {Indorf, A and Kwok, M and Jao, M and Chen, A and Baek, GT and Banerjee, R and Cicero, KI and Cowan, AJ and Portuguese, AJ and Yoon, L and Segal, EM},
title = {Enhancing Multiple Myeloma Care: Implementation of Pharmacist-Led Prescribing of Immunomodulatory Drugs in an Academic Medical Setting.},
journal = {Clinical lymphoma, myeloma & leukemia},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.clml.2025.01.013},
pmid = {40016020},
issn = {2152-2669},
abstract = {BACKGROUND: The oncology healthcare landscape has transformed and has demonstrated the need for efficient care delivery models due to improved survival resulting in larger patient panels. Pharmacists can prescribe oral anticancer agents (OAA), laboratory orders, and supportive care treatments as licensed independent practitioners (LIP) under their pharmacist license. Using immunomodulators (IMiDs) for patients with multiple myeloma (MM) has complexities with regulatory requirements for prescribing. At our institution, the care team was spending about 240 hours per month satisfying regulatory activities. We aim to characterize the effectiveness of pharmacist LIPs for patients with MM receiving IMiD treatment.

METHODS: A multidisciplinary quality improvement team implemented a model for OAA management with pharmacist LIPs. Patients were evaluated for IMiD adherence. Medication possession ratios (MPR) were collected using fill history for patients with 6 months of fill history pre and postpharmacist LIPs involvement, and paired McNemar's Test assessed differences in adherence. A care team survey gauged satisfaction.

RESULTS: The pharmacist patient panel comprised 246 patients. There were similar adherence rates, with an MPR of 96% preintervention and 96.55% postintervention. All survey participants recommended the pharmacist prescriber for IMiDs and reported positive reviews of pharmacist involvement.

CONCLUSION: Management of OAAs by pharmacist LIPs is viable clinical model. The care team reduced their administrative burden while empowering pharmacists to practice at the top of their license. This framework serves as a guide for institutions to adapt and optimize OAA management in an increasingly complex therapeutic landscape.},
}

@article {pmid40015292,
year = {2025},
author = {Haidar, G and Thomas, S and Loubet, P and Baker, RI and Benfield, T and Boonyaratanakornkit, J and Kiertiburanakul, S and Kim, AHJ and Longbrake, EE and Molina, JM and Paredes, R and Tucker, D and Uriel, A and Weinmann-Menke, J and Aksyuk, AA and Clegg, LE and Currie, A and Yang, H and Flyrin, K and Gibbs, M and Shroff, M and Perez, JL and Chang, LJ and Cohen, TS and , },
title = {Efficacy and safety of sipavibart for prevention of COVID-19 in individuals who are immunocompromised (SUPERNOVA): a randomised, controlled, double-blind, phase 3 trial.},
journal = {The Lancet. Infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1016/S1473-3099(24)00804-1},
pmid = {40015292},
issn = {1474-4457},
abstract = {BACKGROUND: Sipavibart is an anti-spike monoclonal antibody that neutralises SARS-CoV-2 with exceptions, including Phe456Leu-containing variants (eg, KP.2* and KP.3*). This trial assessed sipavibart efficacy and safety for prevention of symptomatic COVID-19 in participants who are immunocompromised.

METHODS: In this ongoing, double-blind, international, phase 3 trial, we enrolled participants who were immunocompromised and aged 12 years or older at 197 hospitals, university health centres, and clinical trial units in 18 countries. Participants were randomly allocated 1:1 to a sipavibart group (intramuscular sipavibart 300 mg on days 1 and 181) or a comparator group (tixagevimab 300 mg-cilgavimab 300 mg on day 1 and placebo on day 181 or placebo on days 1 and 181), stratified by previous COVID-19 vaccination and infection status and use of tixagevimab-cilgavimab. The primary efficacy outcomes were symptomatic COVID-19 caused by any variant or symptomatic COVID-19 caused by non-Phe456Leu-containing variants within 181 days of dosing, assessed in the SARS-CoV-2-negative set, comprising all participants without a positive RT-PCR test for SARS-CoV-2 at baseline and who received at least one trial intervention dose. Safety outcomes for adverse events were assessed 90 days following the first dose and for serious adverse events throughout the study in the safety analysis set (ie, all participants who received at least one injection of sipavibart or comparator). This study is registered with ClinicalTrials.gov, NCT05648110.

FINDINGS: Participants were screened from March 31 to Oct 27, 2023; 3349 participants (56·8% female) were randomly assigned: 1674 to the sipavibart group (five no first dose; 1669 sipavibart) and 1675 to the comparator group (nine no first dose; 1105 tixagevimab-cilgavimab and 561 placebo). Within 181 days of dosing, 122 (7·4%) of 1649 participants in the sipavibart group and 178 (10·9%) of 1631 participants in the comparator group had symptomatic COVID-19 due to any variant (relative risk reduction [RRR] 34·9% [97·5% CI 15·0 to 50·1]; p=0·0006), 54 (3·3%) participants in the sipavibart group and 90 (5·5%) participants in the comparator group had symptomatic COVID-19 due to non-Phe456Leu-containing variants (RRR 42·9% [95% CI 19·9 to 59·3]; p=0·0012), and 47 (2·9%) participants in the sipavibart group and 64 (3·9%) participants in the comparator group had symptomatic COVID-19 due to Phe456Leu-containing variants (30·4% [-1·8 to 52·5]). Adverse events occurred in 833 (49·9%) of 1671 participants in the sipavibart group and 857 (51·5%) of 1663 participants in the comparator group within 3 months of the first dose. One COVID-19-related death occurred in the comparator group. Serious adverse events considered related to trial intervention occurred in two (0·1%) of 1671 participants in the sipavibart group and seven (0·4%) of 1663 participants in the comparator group (none fatal). No serious cardiovascular or thrombotic events were considered to be related to sipavibart.

INTERPRETATION: The primary analysis showed efficacy and safety of sipavibart in preventing symptomatic COVID-19 in participants who are immunocompromised when susceptible (ie, non-Phe456Leu-containing) variants dominated, although no efficacy was shown against resistant (ie, Phe456Leu-containing) variants that dominate as of November, 2024.

FUNDING: AstraZeneca.},
}

@article {pmid40014858,
year = {2025},
author = {Nudy, M and Aragaki, AK and Jiang, X and Manson, JE and Shadyab, AH and Jung, SY and Martin, LW and Wild, RA and Womack, C and Mouton, CP and Rossouw, JE and Schnatz, PF},
title = {Long-Term Changes to Cardiovascular Biomarkers After Hormone Therapy in the Women's Health Initiative Hormone Therapy Clinical Trials.},
journal = {Obstetrics and gynecology},
volume = {},
number = {},
pages = {},
pmid = {40014858},
issn = {1873-233X},
abstract = {OBJECTIVE: To assess the long-term changes in cardiovascular biomarkers during the WHI (Women's Health Initiative) hormone therapy (HT) clinical trials of conjugated equine estrogens (CEE) alone and CEE plus medroxyprogesterone acetate (MPA).

METHODS: HT trial participants from the CEE alone (n=1,188, 0.625 mg/d CEE or placebo) and the CEE+MPA (n=1,508, 0.625 mg/d CEE plus continuous 2.5 mg/d MPA or placebo) trials provided blood samples at baseline and after 1, 3, and 6 years. Low-density lipoprotein cholesterol (LDL-C; primary endpoint), high-density lipoprotein cholesterol (HDL-C), triglycerides, total cholesterol, lipoprotein(a), glucose, insulin, and homeostatic model assessment for insulin resistance were measured. Repeated-measures regression models estimated the geometric means of each log-transformed biomarker by restricted maximum likelihood. A constant treatment effect across visits was used to estimate the overall effect, expressed as a ratio of geometric means, and was complemented with geometric means (95% CIs) by randomization group and corresponding ratios of geometric means (95% CI; HT vs placebo) at each visit.

RESULTS: During the intervention phase of the CEE-alone trial, randomization to CEE reduced LDL-C by 11% over 6 years (ratio of geometric means 0.89, 95% CI, 0.88-0.91, P<.001). The overall reduction in LDL-C was similar for CEE+MPA relative to placebo (ratio of geometric means 0.88, 95% CI, 0.86-0.89, P<.001). Relative to placebo, HDL-C and triglycerides were 13.0% and 7.0% higher with CEE and CEE+MPA, respectively. The homeostatic model assessment for insulin resistance decreased by 14.0% and 8.0% for CEE-alone and CEE+MPA trial participants, respectively. Relative to placebo, lipoprotein(a) decreased by 15.0% and 20.0% for participants randomized to CEE alone and CEE+MPA, respectively.

CONCLUSION: Lipoprotein(a), LDL-C, and homeostatic model assessment for insulin resistance were lower and HDL-C levels were higher for HT compared with placebo. Triglycerides increased in both the CEE and CEE+MPA trials, however. Future research should assess whether other progestogens attenuate the effect of estrogen on HDL-C. These results may be used to counsel younger menopausal women with bothersome symptoms who are deciding whether to initiate oral HT within the context of published effects of oral HT on rates of cardiovascular events.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT00000611.},
}

@article {pmid40014323,
year = {2025},
author = {Hirayama, AV and Bleakley, M},
title = {Competition for CD19 binding may accelerate CAR efficacy.},
journal = {Blood},
volume = {145},
number = {9},
pages = {902-903},
doi = {10.1182/blood.2024027469},
pmid = {40014323},
issn = {1528-0020},
}

@article {pmid40013681,
year = {2025},
author = {Childers, CP and Petty, AM and Selzer, DJ and Senkowski, CK},
title = {Obesity and Work in Abdominal Surgery.},
journal = {Journal of the American College of Surgeons},
volume = {},
number = {},
pages = {},
doi = {10.1097/XCS.0000000000001367},
pmid = {40013681},
issn = {1879-1190},
abstract = {BACKGROUND: Recent analyses have shown that Modifier 22 does not reimburse surgeons for the increased work required to care for the most complex patients. New strategies are needed to identify patients that require additional work to create a financial system that ensures equitable access. Obesity has been identified as a growing and potentially reliable patient risk factor that could be used to identify cases that require additional work.

STUDY DESIGN: Using 2022 ACS NSQIP data, this study evaluated 10 common general surgery operations (appendectomy, cholecystectomy, colon/rectal operations, hernia repairs). The primary predictor was BMI category (Normal: 18.5-25, overweight: 25-29.9, class I obesity: 30-34.9, class II obesity: 35-39.9, class III obesity 40-49.9, extreme obesity >=50). Primary outcomes were operative time and composite measures of complications.

RESULTS: The final sample included 158,692 operations. Across the entire cohort, 22.2% were normal weight and 76.3% were overweight or obese. Overall, operative time was increased by 5.6% (95% CI 4.8-6.3%) for overweight, by 10.6% (CI 9.8-11.5%) for class I obesity, by 14.7% (CI 13.6-15.8%) for class II obesity, by 18.9% (CI 17.6-20.2%) for class III obesity, and by 26.8% (CI 14.1-29.6%) for extreme obesity compared to those with normal BMI. Obesity was associated with higher odds of any complication or serious complication, driven by wound complications, pulmonary emboli, and renal insufficiency.

CONCLUSION: Obesity is a growing challenge in abdominal surgery and is associated with increase operative time and risk of complications. The consistency of the magnitude of effect makes it an ideal target for a modifier or add-on code that could identify cases requiring additional work.},
}

@article {pmid40013392,
year = {2025},
author = {Haney, M and Ashraf, A and Lake, KE and Strecker, L and Myers, KC and Towe, C and Walkup, L and Woods, J and Edwards, SL and Cooper, R and Lehmann, LE and Cisneros, GS and Freedman, JL and Baker, KS and Doherty, E and MacMillan, ML and Goldfarb, SB and Davies, SM and Koo, J and Groups, T},
title = {Community respiratory viruses are generally well-tolerated in hematopoietic stem cell transplant recipients: a brief report from the TRANSPIRE study.},
journal = {Haematologica},
volume = {},
number = {},
pages = {},
doi = {10.3324/haematol.2024.287107},
pmid = {40013392},
issn = {1592-8721},
abstract = {Not available.},
}

@article {pmid40009771,
year = {2025},
author = {Collin, LJ and Cushing-Haugen, KL and Terry, KL and Goode, EL and Wu, AH and Harris, HR and Sasamoto, N and Cramer, DW and Modugno, F and Elishaev, E and Fu, Z and Moysich, KB and Fasching, PA and Pearce, CL and Menon, U and Gentry-Maharaj, A and Gayther, SA and Wentzensen, N and Goodman, MT and George, J and Talhouk, A and Anglesio, MS and Ramus, SJ and Bowtell, DD and Tworoger, SS and Schildkraut, JM and Webb, PM and Doherty, JA},
title = {Patterns of associations with epidemiologic factors by high grade serous ovarian cancer gene expression subtypes.},
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-24-1143},
pmid = {40009771},
issn = {1538-7755},
abstract = {BACKGROUND: Ovarian high-grade serous carcinomas (HGSC) comprise four distinct molecular subtypes based on mRNA expression patterns, with differential survival. Understanding risk factor associations is important to elucidate the etiology of HGSC. We investigated associations between different epidemiologic risk factors and HGSC molecular subtypes.

METHODS: We pooled data from 11 case-control studies with epidemiologic and tumor gene expression data from custom NanoString CodeSets developed through a collaboration within the Ovarian Tumor Tissue Analysis Consortium. The PrOTYPE validated NanoString-based 55 gene classifier was used to assign HGSC gene expression subtypes. We examined associations between epidemiologic factors and HGSC subtypes in 2,070 cases and 16,633 controls using multivariable-adjusted polytomous regression models.

RESULTS: Among the 2,070 HGSC cases, 556 (27%) were classified as C1.MES, 340 (16%) as C5.PRO, 538 (26%) as C2.IMM, and 636 (31%) as C4.DIF. Key factors, including oral contraceptive use, parity, breastfeeding, and family history of ovarian cancer, were similarly associated with all subtypes. Heterogeneity was observed for several factors. Former smoking (OR=1.25, 95%CI: 1.03, 1.51) and genital powder use (OR=1.42, 95%CI: 1.08, 1.86) were uniquely associated with C2.IMM. History of endometriosis was associated with C5.PRO (OR=1.46, 95%CI: 0.98, 2.16) and C4.DIF (OR=1.27, 95%CI: 0.94, 1.71) only. Family history of breast cancer (OR=1.44, 95%CI: 1.16, 1.78) and current smoking (OR=1.40, 95%CI: 1.11, 1.76) were associated with C4.DIF only.

CONCLUSIONS: This study observed heterogeneous associations of epidemiologic and modifiable factors with HGSC molecular subtypes.

IMPACT: The different patterns of associations may provide key information about the etiology of the four subtypes.},
}

@article {pmid40007996,
year = {2025},
author = {Crotty, EE and Sato, AA and Abdelbaki, MS},
title = {Integrating MAPK pathway inhibition into standard-of-care therapy for pediatric low-grade glioma.},
journal = {Frontiers in oncology},
volume = {15},
number = {},
pages = {1520316},
pmid = {40007996},
issn = {2234-943X},
abstract = {Pediatric low-grade gliomas (pLGG) are a group of tumors largely driven by alterations in a single genetic pathway, known as the RAS-RAF-mitogen-activated protein kinase (MAPK) pathway. Recent biologic insights and therapeutic targeting of MAPK-alterations have dramatically shifted the treatment approach in pLGG. While chemotherapy remains front-line therapy for unresectable pLGG in most scenarios (with the notable exception of BRAF [V600E]-altered tumors), many patients recur following cytotoxic agents and require further treatment. Inhibitors of the MAPK pathway, primarily MEK and RAF kinase inhibitors, have emerged as effective and tolerable second-line or later therapy for pLGG. As familiarity with these targeted agents increases, their indications for use continue to expand and Phase 3 clinical trials investigating their utility in the front-line setting are ongoing. We have adopted mitigation strategies for their associated toxicities; skin toxicity, in particular, is now managed by prevention strategies and early dermatologic intervention. This review highlights current approaches for the clinical implementation of MEK and RAF kinase inhibitors for pLGG, focusing on the practical aspects of drug administration, toxicity management, response monitoring, and distribution to patients experiencing geographic or financial barriers to care. Additionally, we review important considerations for the off-label use of these agents while contemporaneous clinical trials assessing front-line efficacy are ongoing. We discuss the potential for more expansive or histology-agnostic tumor targeting using MEK inhibitors, harnessing their biologic relevance for other RAS-altered conditions.},
}

@article {pmid40006680,
year = {2025},
author = {Shen, X and Korber, B and Spreng, RL and Sawant, SS and deCamp, A and McMillan, AS and Mathura, R and Zolla-Pazner, S and Pinter, A and Parks, R and Bowman, C and Sutherland, L and Scearce, R and Yates, NL and Montefiori, DC and Haynes, BF and Tomaras, GD},
title = {A Pentavalent HIV-1 Subtype C Vaccine Containing Computationally Selected gp120 Strains Improves the Breadth of V1V2 Region Responses.},
journal = {Vaccines},
volume = {13},
number = {2},
pages = {},
pmid = {40006680},
issn = {2076-393X},
support = {HHSN27201100016C/AI/NIAID NIH HHS/United States ; AI067854//Center for HIV/AIDS Vaccine Immunology/ ; AI100645//Duke Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery/ ; P30AI064518//Duke Center for AIDS Research/ ; },
abstract = {BACKGROUND: HIV-1 envelope (Env) variable loops 1 and 2 (V1V2) directed non-neutralizing antibodies were a correlate of decreased transmission risk in the RV144 vaccine trial. Thus, the elicitation and breadth of antibody responses against the V1V2 of HIV-1 Env are important considerations for HIV-1 vaccine candidates. The V1V2 region's highly variable nature and the extensive diversity of subtype C HIV-1 Envelopes (Envs) make the V1V2 response breadth a high priority for HIV-1 vaccine regimens aiming for V1V2-mediated protection in Southern Africa. Here, we determined whether the breadth of the anti-V1V2 vaccine response can be broadened by including HIV-1 Env strains computationally designed to enhance the coverage of subtype C V1V2 sequence diversity.

METHODS: Three subtype C Env strains were selected to maximize antibody binding coverage while complementing subtype C vaccine gp120s that were given in human clinical trials in South Africa, as well as to improve epitope accessibility. Humoral immunogenicity of a novel trivalent gp120 vaccine immunogen, a bivalent gp120 boost already in clinical trials (1086C and TV1), and a pentavalent (all five gp120s combined) were evaluated in a preclinical immunization study in guinea pigs. The pentavalent combination was further evaluated with alum versus glucopyranosyl lipid adjuvants formulated in squalene-in-water emulsion (GLA-SE) adjuvants in non-human primates. The breadth of the anti-V1V2 response was assessed using an array of cross-subtype variable loops 1&2 (V1V2) scaffold proteins and linear V2 peptides.

RESULTS: The breadth of the IgG response against V1V2 antigens of the trivalent and pentavalent groups was comparable, and both were greater than the breadth of the bivalent group. Linear epitope mapping showed that two linear epitopes in V2 were targeted by the vaccinated animals: the V2 hotspot focused at [169]K that potentially correlated with decreased HIV-1 risk in RV144 and the V2.2 site ([179]LDV/I[181]) that is part of the integrin α4β7 binding site. The bivalent vaccine elicited a significantly higher magnitude of binding to the V2 hotspot compared to the trivalent vaccine whereas the trivalent vaccine elicited significantly higher binding to the V2.2 epitope compared to the bivalent vaccine, while the pentavalent recognized both regions.

CONCLUSIONS: These results demonstrate that the three new computationally selected subtype C Envs successfully complemented 1086C and TV1 for broader V1V2 antibody responses, and, in concert with adjuvants that stimulate V1V2 responses, can be considered as part of a rationale immunogen design to improve V1V2 IgG coverage in future vaccine trials in South Africa.},
}

@article {pmid39990376,
year = {2025},
author = {Wang, Y and Gornalusse, GG and Siegel, DA and Barbehenn, A and Hoh, R and Martin, J and Hecht, F and Pilcher, C and Semenova, L and Murdoch, DM and Margolis, DM and Levy, CN and Jerome, KR and Rudin, CD and Hladik, F and Deeks, SG and Lee, SA and Browne, EP},
title = {NF-κB dependent gene expression and plasma IL-1β, TNFα and GCSF drive transcriptomic diversity and CD4:CD8 ratio in people with HIV on ART.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39990376},
issn = {2692-8205},
support = {R01 DA054994/DA/NIDA NIH HHS/United States ; K23 GM112526/GM/NIGMS NIH HHS/United States ; R01 AI143381/AI/NIAID NIH HHS/United States ; R01 AI184122/AI/NIAID NIH HHS/United States ; KL2 TR002317/TR/NCATS NIH HHS/United States ; P30 AI027757/AI/NIAID NIH HHS/United States ; UM1 AI164567/AI/NIAID NIH HHS/United States ; UM1 AI126623/AI/NIAID NIH HHS/United States ; },
abstract = {Despite antiretroviral therapy (ART), people with HIV (PWH) on ART experience higher rates of morbidity and mortality vs. age-matched HIV negative controls, which may be driven by chronic inflammation due to persistent virus. We performed bulk RNA sequencing (RNA-seq) on peripheral CD4+ T cells, as well as quantified plasma immune marker levels from 154 PWH on ART to identify host immune signatures associated with immune recovery (CD4:CD8) and HIV persistence (cell-associated HIV DNA and RNA). Using a novel dimension reduction tool - Pairwise Controlled Manifold Approximation (PaCMAP), we defined three distinct participant transcriptomic clusters. We found that these three clusters were largely defined by differential expression of genes regulated by the transcription factor NF-κB. While clustering was not associated with HIV reservoir size, we observed an association with CD4:CD8 ratio, a marker of immune recovery and prognostic factor for mortality in PWH on ART. Furthermore, distinct patterns of plasma IL-1β, TNF-α and GCSF were also strongly associated with the clusters, suggesting that these immune markers play a key role in CD4+ T cell transcriptomic diversity and immune recovery in PWH on ART. These findings reveal novel subgroups of PWH on ART with distinct immunological characteristics, and define a transcriptional signature associated with clinically significant immune parameters for PWH. A deeper understanding of these subgroups could advance clinical strategies to treat HIV-associated immune dysfunction.},
}

@article {pmid39975454,
year = {2025},
author = {Xie, T and Richman, H and Gao, J and Matsen, FA and Zhang, C},
title = {PhyloVAE: Unsupervised Learning of Phylogenetic Trees via Variational Autoencoders.},
journal = {ArXiv},
volume = {},
number = {},
pages = {},
pmid = {39975454},
issn = {2331-8422},
support = {R01 AI162611/AI/NIAID NIH HHS/United States ; },
abstract = {Learning informative representations of phylogenetic tree structures is essential for analyzing evolutionary relationships. Classical distance-based methods have been widely used to project phylogenetic trees into Euclidean space, but they are often sensitive to the choice of distance metric and may lack sufficient resolution. In this paper, we introduce phylogenetic variational autoencoders (PhyloVAEs), an unsupervissed learning framework designed for representation learning and generative modeling of tree topologies. Leveraging an efficient encoding mechanism inspired by autoregressive tree topology generation, we develop a deep latent-variable generative model that facilitates fast, parallelized topology generation. PhyloVAE combines this generative model with a collaborative inference model based on learnable topological features, allowing for high-resolution representations of phylogenetic tree samples. Extensive experiments demonstrate PhyloVAE's robust representation learning capabilities and fast generation of phylogenetic tree topologies.},
}

@article {pmid39975229,
year = {2025},
author = {Shi, Z and Tsuge, M and Collier, N and Takeuchi, Y and Uchida, T and Rutter, CM and Teraoka, Y and Uprichard, S and Ishida, Y and Tateno, C and Ozik, J and Dahari, H and Chayama, K},
title = {Modeling of hepatitis B virus infection spread in primary human hepatocytes.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39975229},
issn = {2692-8205},
support = {R01 AI144112/AI/NIAID NIH HHS/United States ; R01 AI146917/AI/NIAID NIH HHS/United States ; },
abstract = {Chronic hepatitis B virus (HBV) infection poses a significant global health threat, causing severe liver diseases including cirrhosis and hepatocellular carcinoma. We characterized HBV DNA kinetics in primary human hepatocytes (PHH) over 32 days post-inoculation (pi) and used agent-based modeling (ABM) to gain insights into HBV lifecycle and spread. Parallel PHH cultures were mock-treated or HBV entry inhibitor Myr-preS1 (6.25 μg/mL) was initiated 24h pi. In untreated PHH, 3 viral DNA kinetic patterns were identified: (1) an initial decline, followed by (2) rapid amplification, and (3) slower amplification/accumulation. In the presence of Myr-preS1, viral DNA and infected cell numbers in phase 3 were effectively blocked, with minimal to no increase. This suggests that phase 2 represents viral amplification in initially infected cells, while phase 3 corresponds to viral spread to naïve cells. The ABM reproduced well the HBV kinetic patterns observed and predicted that the viral eclipse phase lasts between 18 and 38 hours. After the eclipse phase, the viral production rate increases over time, starting with a slow production cycle of 1 virion per day, which gradually accelerates to 1 virion per hour after 3 days. Approximately 4 days later, virion production reaches a steady state production rate of 4 virions/hour. The estimated median efficacy of Myr-preS1 in blocking HBV spread was 91% (range: 90-92%). The HBV kinetics and the predicted estimates of the HBV eclipse phase duration and HBV production cycles in PHH are similar of those predicted in uPA/SCID mice with human livers.},
}

@article {pmid39975131,
year = {2025},
author = {Barrero, DJ and Hedouin, S and Mao, Y and Asbury, CL and Stergachis, A and O'Toole, E and Biggins, S},
title = {Centromeres in the thermotolerant yeast K. marxianus mediate attachment to a single microtubule.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39975131},
issn = {2692-8205},
support = {DP5 OD029630/OD/NIH HHS/United States ; R35 GM134842/GM/NIGMS NIH HHS/United States ; R35 GM149357/GM/NIGMS NIH HHS/United States ; },
abstract = {Eukaryotic chromosome segregation requires spindle microtubules to attach to chromosomes through kinetochores. The chromosomal locus that mediates kinetochore assembly is the centromere and is epigenetically specified in most organisms by a centromeric histone H3 variant called CENP-A. An exception to this is budding yeast which have short, sequenced-defined point centromeres. In S. cerevisiae, a single CENP-A nucleosome is formed at the centromere and is sufficient for kinetochore assembly. The thermophilic budding yeast Kluyveromyces marxianus also has a point centromere but its length is nearly double the S. cerevisiae centromere and the number of centromeric nucleosomes and kinetochore attachment sites is unknown. Purification of native kinetochores from K. marxianus yielded a mixed population, with one subpopulation that appeared to consist of doublets, making it unclear whether K. marxianus shares the same attachment architecture as S. cerevisiae. Here, we demonstrate that though the doublet kinetochores have a functional impact on kinetochore strength, kinetochore localization throughout the cell cycle appears conserved between these two yeasts. In addition, whole spindle electron tomography demonstrates that a single microtubule binds to each chromosome. Single-molecule nucleosome mapping analysis suggests the presence of a single centromeric nucleosome. Taken together, we propose that the K. marxianus point centromere assembles a single centromeric nucleosome that mediates attachment to one microtubule.},
}

@article {pmid39973981,
year = {2025},
author = {Gustav, M and van Treeck, M and Reitsam, NG and Carrero, ZI and Loeffler, CML and Meneghetti, AR and Märkl, B and Boardman, LA and French, AJ and Goode, EL and Gsur, A and Brezina, S and Gunter, MJ and Murphy, N and Hönscheid, P and Sperling, C and Foersch, S and Steinfelder, R and Harrison, T and Peters, U and Phipps, A and Kather, JN},
title = {Assessing Genotype-Phenotype Correlations with Deep Learning in Colorectal Cancer: A Multi-Centric Study.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {39973981},
support = {75N92021D00002/HL/NHLBI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; R01 CA107333/CA/NCI NIH HHS/United States ; S10 OD028685/OD/NIH HHS/United States ; U01 CA137088/CA/NCI NIH HHS/United States ; P20 CA252733/CA/NCI NIH HHS/United States ; 75N92021D00001/HL/NHLBI NIH HHS/United States ; 75N92021D00003/WH/WHI NIH HHS/United States ; 75N92021D00004/WH/WHI NIH HHS/United States ; HHSN268201700006C/HL/NHLBI NIH HHS/United States ; 75N92021D00005/WH/WHI NIH HHS/United States ; HHSN261201000032C/CA/NCI NIH HHS/United States ; },
abstract = {BACKGROUND: Deep Learning (DL) has emerged as a powerful tool to predict genetic biomarkers directly from digitized Hematoxylin and Eosin (H&E) slides in colorectal cancer (CRC). However, few studies have systematically investigated the predictability of biomarkers beyond routinely available alterations such as microsatellite instability (MSI), and BRAF and KRAS mutations.

METHODS: Our primary dataset comprised H&E slides of CRC tumors across five cohorts totaling 1,376 patients who underwent comprehensive panel sequencing, with an additional 536 patients from two public datasets for validation. We developed a DL model using a single transformer model to predict multiple genetic alterations directly from the slides. The model's performance was compared against conventional single-target models, and potential confounders were analyzed.

FINDINGS: The multi-target model was able to predict numerous biomarkers from pathology slides, matching and partly exceeding single-target transformers. The Area Under the Receiver Operating Characteristic curve (AUROC, mean ± std) on the primary external validation cohorts was: BRAF (0·78 ± 0·01), hypermutation (0·88 ± 0·01), MSI (0·93 ± 0·01), RNF43 (0·86 ± 0·01); this biomarker predictability was mirrored across metrics and co-occurrence analyses. However, biomarkers with high AUROCs largely correlated with MSI, with model predictions depending considerably on MSI-associated morphology upon pathological examination.

INTERPRETATION: Our study demonstrates that multi-target transformers can predict the biomarker status for numerous genetic alterations in CRC directly from H&E slides. However, their predictability is mainly associated with MSI phenotype, despite indications of slight biomarker-inherent contributions to a phenotype. Our findings underscore the need to analyze confounders in AI-based oncology biomarkers. To enable this, we developed a validated model applicable to other cancers and larger, diverse datasets.

FUNDING: The German Federal Ministry of Health, the Max-Eder-Programme of German Cancer Aid, the German Federal Ministry of Education and Research, the German Academic Exchange Service, and the EU.},
}

@article {pmid39786430,
year = {2025},
author = {Lee, SM and Hamid, O and Jotte, R and Zakharia, Y and Medina, T and Gillespie-Twardy, A and Mehmi, I and Chandra, S and Watson, G and Ward, P and Chaney, M and Lu, H and Berndt, J and O'Connor, BP and Rathi, K and Shaikh, E and Cowey, CL},
title = {Phase II Open-Label Trial of Brentuximab Vedotin with Pembrolizumab in PD-1-Pretreated Metastatic Non-Small Cell Lung Cancer and Metastatic Cutaneous Melanoma.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {31},
number = {5},
pages = {848-859},
doi = {10.1158/1078-0432.CCR-24-1478},
pmid = {39786430},
issn = {1557-3265},
support = {//Pfizer Foundation/ ; },
mesh = {Humans ; *Antibodies, Monoclonal, Humanized/administration & dosage/therapeutic use/adverse effects ; Female ; Male ; Middle Aged ; *Melanoma/drug therapy/pathology/mortality ; Aged ; *Carcinoma, Non-Small-Cell Lung/drug therapy/pathology/mortality ; Adult ; *Skin Neoplasms/drug therapy/pathology/mortality ; *Lung Neoplasms/drug therapy/pathology/secondary/mortality ; Aged, 80 and over ; *Brentuximab Vedotin/therapeutic use/administration & dosage ; *Programmed Cell Death 1 Receptor/antagonists & inhibitors ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects ; Melanoma, Cutaneous Malignant ; },
abstract = {PURPOSE: Brentuximab vedotin (BV) is hypothesized to selectively deplete T regulatory cells that express CD30 and resensitize tumors to anti-PD-1 therapy. This study evaluated responses to BV + pembrolizumab after PD-1 therapy and explored corresponding biomarkers.

PATIENTS AND METHODS: A total of 55 patients with metastatic non-small cell lung cancer and 58 patients with metastatic cutaneous melanoma received ≥1 dose of BV + pembrolizumab. Patients had received a median of 2.0 prior lines of systemic therapies (range, 1-7). The primary endpoint was confirmed objective response rate (ORR). Exploratory endpoints included overall survival (OS) and biomarker analysis in blood and tumor.

RESULTS: For the secondary refractory metastatic non-small cell lung cancer cohort (RECIST v1.1), the ORR was 14%, median progression-free survival (PFS) was 5.85 months, and median OS was 14.4 months. For the secondary refractory metastatic cutaneous melanoma cohort (immune RECIST), the ORR was 24%, median PFS was 4.44 months, and median OS was 21.9 months. Overall, the median duration of OS follow-up was 17.2 months (95% confidence interval, 14.62-22.87). No new safety signals were identified. No treatment-related grade 5 toxicity was seen. Longitudinal immune phenotyping in peripheral blood demonstrated a transient decrease in T regulatory cells. Paired tumor biopsies from baseline and cycle 3 day 1 showed a trend of increased CD8 T-cell infiltration, especially in responding patients.

CONCLUSIONS: BV + pembrolizumab in solid tumor malignancies resulted in clinically meaningful, durable responses with encouraging OS and PFS rates supportive of the immunomodulatory activity of this combination. Stronger antitumor activity was observed in secondary refractory cohorts. The safety profile of this combination was consistent with the individual drug risk profiles.},
}

Humans
*Antibodies, Monoclonal, Humanized/administration & dosage/therapeutic use/adverse effects
Female
Male
Middle Aged
*Melanoma/drug therapy/pathology/mortality
Aged
*Carcinoma, Non-Small-Cell Lung/drug therapy/pathology/mortality
Adult
*Skin Neoplasms/drug therapy/pathology/mortality
*Lung Neoplasms/drug therapy/pathology/secondary/mortality
Aged, 80 and over
*Brentuximab Vedotin/therapeutic use/administration & dosage
*Programmed Cell Death 1 Receptor/antagonists & inhibitors
Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects
Melanoma, Cutaneous Malignant

@article {pmid40006664,
year = {2025},
author = {Gwin, WR and Salazar, LG and Dai, JY and Higgins, D and Coveler, AL and Childs, JS and Blancas, R and Dang, Y and Reichow, J and Slota, M and Lu, H and Disis, ML},
title = {A Phase II Study of Denileukin Diftitox in Patients with Advanced Treatment Refractory Breast Cancer.},
journal = {Vaccines},
volume = {13},
number = {2},
pages = {},
pmid = {40006664},
issn = {2076-393X},
abstract = {Background/Objectives: Regulatory T cells (Treg) suppress immunity in the tumor microenvironment, are linked to poor prognosis across breast cancer subtypes, and suppress the cytolytic function of cytotoxic CD8+ T cells. Denileukin diftitox, a diphtheria toxin (DT)/IL-2 fusion protein, targets and depletes Tregs. This Phase II study aimed to assess the safety of denileukin diftitox and its effect on Tregs and tumor growth in patients with advanced breast cancer. Methods: This single-arm Phase II study of denileukin diftitox enrolled patients with refractory stage IV breast cancer. Patients received denileukin diftitox 18 mcg/kg/day IV for Days 1-5 every 21 days for up to six cycles. Toxicity was assessed using CTCAE v3.0 and tumor response was evaluated per RECIST criteria. Blood samples were collected to analyze Tregs by flow cytometry and anti-DT antibodies by ELISA. Results: Fifteen patients with stage IV breast cancer were enrolled. Four patients completed all planned denileukin diftitox infusions and achieved stable disease (27%, 95% CI [0.08, 0.55]). Two patients (13%) discontinued due to toxicity, and nine patients (60%) discontinued due to progressive disease. Eleven patients experienced at least one grade 3 or 4 adverse event. Although there was a general reduction in peripheral blood Tregs, the difference in CD4+CD25+FOXP3+ Tregs levels post-treatment was not statistically significant (p = 0.10). Six patients (40%) achieved ≥25% reductions in Tregs. A significant increase in anti-DT IgG antibodies was observed post-treatment (p < 0.005). Conclusions: Denileukin diftitox demonstrated moderate toxicity in this advanced breast cancer cohort. Denileukin diftitox modulated regulatory T cells. However, the majority of patients experienced disease progression in the study.},
}

@article {pmid40004846,
year = {2025},
author = {Costa, BA and Dima, D and Mark, T and Sadek, NL and Ijioma, S and Ray, D and Goel, U and Dranitsaris, G and Sheng, T and Moshier, E and Mouhieddine, TH and Khouri, J and Rossi, A},
title = {Impact of Prior Selinexor Exposure on Outcomes of Chimeric Antigen Receptor T-Cell Therapy for Relapsed/Refractory Multiple Myeloma: An Exploratory Analysis.},
journal = {Journal of clinical medicine},
volume = {14},
number = {4},
pages = {},
pmid = {40004846},
issn = {2077-0383},
support = {NA//Karyopharm Therapeutics/ ; },
abstract = {Background/Objectives: Chimeric antigen receptor T-cell therapy (CAR-T) has become a key treatment option for relapsed/refractory multiple myeloma (RRMM), but factors impairing T-cell fitness may diminish efficacy. Our exploratory analysis aimed to evaluate the impact of prior treatment with a selinexor-containing regimen on CAR-T outcomes for RRMM patients. Methods: Data for this retrospective cohort study were sourced from electronic medical records at two US academic centers. Kaplan-Meier estimates assessed duration of response (DOR), progression-free survival (PFS), and overall survival (OS), reported as medians with interquartile ranges (IQRs). Cox proportional hazards regression analyzed factors potentially associated with PFS and OS, reported as hazard ratios (HRs) with 95% confidence intervals (CIs). Results: Among 45 patients exposed to selinexor before undergoing BCMA-directed CAR-T, median therapy line numbers for selinexor use and CAR-T were 7 and 9, respectively, with 24.4% receiving selinexor as part of bridging. At median follow-up of 68 months, median PFS and OS post CAR-T were 8.0 (IQR 3.1-39.5) and 35.9 (IQR 14.2-NR) months, respectively. Overall response rate to CAR-T was 89%, with a median DOR of 8.1 months (IQR 2.9-39.0). In our multivariable model, patients who received a selinexor-based regimen in the line of therapy preceding CAR-T showed a trend toward reduced risk of death (HR = 0.08; 95% CI 0.02-0.46) and/or disease progression (HR = 0.40; 95% CI 0.14-1.09). Conclusions: Prior selinexor exposure does not appear to compromise CAR-T outcomes in heavily pretreated RRMM, suggesting potential T-cell sparing. Our findings warrant larger, prospective studies to determine whether preemptive selinexor treatment can optimize CAR-T efficacy.},
}

@article {pmid40000903,
year = {2025},
author = {Itkin, T and Houghton, S and Schreiner, R and Lin, Y and Badwe, CR and Voisin, V and Murison, A and Seyedhassantehrani, N and Kaufmann, KB and Garcia-Prat, L and Booth, GT and Geng, F and Liu, Y and Gomez-Salinero, JM and Shieh, JH and Redmond, D and Xiang, JZ and Josefowicz, SZ and Trapnell, C and Pietras, EM and Spencer, JA and Levine, R and Xiao, W and Zangi, L and Hadland, B and Dick, JE and Xie, SZ and Rafii, S},
title = {Transcriptional activation of regenerative hematopoiesis via microenvironmental sensing.},
journal = {Nature immunology},
volume = {},
number = {},
pages = {},
pmid = {40000903},
issn = {1529-2916},
abstract = {Transition between activation and quiescence states in hematopoietic stem and progenitor cells (HSPCs) is tightly governed by cell-intrinsic means and microenvironmental co-adaptation. Although this balance is fundamental for lifelong hematopoiesis and immunity, the underlying molecular mechanisms remain poorly defined. Multimodal analysis divulging differential transcriptional activity between distinct HSPC states indicates the presence of Fli-1 transcription factor binding motif in activated hematopoietic stem cells. We reveal that Fli-1 activity is essential during regenerative hematopoiesis in mice. Fli-1 directs activation programs while priming cellular sensory and output machineries, enabling HSPCs co-adoptability with a stimulated vascular niche through propagation of niche-derived angiocrine Notch1 signaling. Constitutively induced Notch1 signaling is sufficient to recuperate functional hematopoietic stem cells impairments in the absence of Fli-1, without leukemic transformation. Applying FLI-1 transient modified-mRNA transduction into latent adult human mobilized HSPCs, enables their niche-mediated expansion and superior engraftment capacities. Thus, decryption of stem cell activation programs offers valuable insights for immunological regenerative medicine.},
}

@article {pmid39999848,
year = {2025},
author = {Ugalde-Morales, E and Wilf, R and Pluta, J and Ploner, A and Fan, M and Damra, M and Aben, KK and Anson-Cartwright, L and Chen, C and Cortessis, VK and Daneshmand, S and Ferlin, A and Gamulin, M and Gietema, JA and Gonzalez-Niera, A and Grotmol, T and Hamilton, RJ and Harland, M and Haugen, TB and Hauser, R and Hildebrandt, MAT and Karlsson, R and Kiemeney, LA and Kim, J and Lessel, D and Lothe, RA and Loveday, C and Chanock, SJ and McGlynn, KA and Meijer, C and Nead, KT and Nsengimana, J and Popovic, M and Rafnar, T and Richiardi, L and Rocca, MS and Schwartz, SM and Skotheim, RI and Stefansson, K and Stewart, DR and Turnbull, C and Vaughn, DJ and Winge, SB and Zheng, T and Monteiro, AN and Almstrup, K and Kanetsky, PA and Nathanson, KL and Wiklund, F and , },
title = {Identification of genes associated with testicular germ cell tumor susceptibility through a transcriptome-wide association study.},
journal = {American journal of human genetics},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajhg.2025.01.022},
pmid = {39999848},
issn = {1537-6605},
abstract = {Transcriptome-wide association studies (TWASs) have the potential to identify susceptibility genes associated with testicular germ cell tumors (TGCTs). We conducted a comprehensive TGCT TWAS by integrating genome-wide association study (GWAS) summary data with predicted expression models from normal testis, TGCT tissues, and a cross-tissue panel that encompasses shared regulatory features across 22 normal tissues, including the testis. Gene associations were evaluated while accounting for variant-level effects from GWASs, followed by fine-mapping analyses in regions exhibiting multiple TWAS signals, and finally supplemented by colocalization analysis. Expression and protein patterns of identified TWAS genes were further examined in relevant tissues. Our analysis tested 19,805 gene-disease links, revealing 165 TGCT-associated genes with a false discovery rate of less than 0.01. We prioritized 46 candidate genes by considering GWAS-inflated signals, correlations between neighboring genes, and evidence of colocalization. Among these, 23 genes overlap with 22 GWAS loci, with 7 being associations not previously implicated in TGCT risk. Additionally, 23 genes located within 21 loci are at least 1 Mb away from published GWAS index variants. The 46 prioritized genes display expression levels consistent with expected expression levels in human gonadal cell types and precursor tumor cells and significant enrichment in TGCTs. Additionally, immunohistochemistry revealed protein-level accumulation of two candidate genes, ARID3B and GINM1, in both precursor and tumor cells. These findings enhance our understanding of the genetic predisposition to TGCTs and underscore the importance of further functional investigations into these candidate genes.},
}

@article {pmid39996762,
year = {2025},
author = {Gang, M and Othus, M and Walter, RB},
title = {Significance of Measurable Residual Disease in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia.},
journal = {Cells},
volume = {14},
number = {4},
pages = {},
pmid = {39996762},
issn = {2073-4409},
support = {T32-HL007093//NIH/NHLBI/ ; },
mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/methods ; *Leukemia, Myeloid, Acute/therapy ; *Neoplasm, Residual ; *Transplantation, Homologous ; },
abstract = {Allogeneic hematopoietic cell transplantation (HCT) remains an important curative-intent treatment for many patients with acute myeloid leukemia (AML), but AML recurrence after allografting is common. Many factors associated with relapse after allogeneic HCT have been identified over the years. Central among these is measurable ("minimal") residual disease (MRD) as detected by multiparameter flow cytometry, quantitative polymerase chain reaction, and/or next-generation sequencing. Demonstration of a strong, independent prognostic role of pre- and early post-HCT MRD has raised hopes MRD could also serve as a predictive biomarker to inform treatment decision-making, with emerging data indicating the potential value to guide candidacy assessment for allografting as a post-remission treatment strategy, the selection of conditioning intensity, use of small molecule inhibitors as post-HCT maintenance therapy, and preemptive infusion of donor lymphocytes. Monitoring for leukemia recurrence after HCT and surrogacy for treatment response are other considerations for the clinical use of MRD data. In this review, we will outline the current landscape of MRD as a biomarker for patients with AML undergoing HCT and discuss areas of uncertainty and ongoing research.},
}

Humans
*Hematopoietic Stem Cell Transplantation/methods
*Leukemia, Myeloid, Acute/therapy
*Neoplasm, Residual
*Transplantation, Homologous

@article {pmid39996711,
year = {2025},
author = {Morishita, T and Martin, PJ and Inamoto, Y},
title = {Treatment Response in Individual Organs Affected by Chronic Graft-Versus-Host Disease.},
journal = {Cells},
volume = {14},
number = {4},
pages = {},
pmid = {39996711},
issn = {2073-4409},
support = {22K08517//Japan Society for the Promotion of Science/ ; },
mesh = {*Graft vs Host Disease/therapy ; Humans ; Chronic Disease ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Treatment Outcome ; Organ Specificity ; },
abstract = {Chronic graft-versus-host disease (GVHD) occurs in 30-70% of patients after allogeneic hematopoietic cell transplantation (HCT) and increases the risks of morbidity and mortality. Systemic corticosteroids are the standard initial treatment, but one-third of patients require subsequent treatment with other systemic agents. Treatment decisions are often based on physicians' experience. The expected treatment response rates in specific organs affected by chronic GVHD may inform such decisions. In this review, we identify 20 studies reporting treatment response rates in individual organs according to objective criteria, summarize the results, discuss the caveats in data interpretation, identify the unmet needs, and suggest future directions in the field. For cutaneous sclerosis, we observed large discrepancies in organ response rates according to the current NIH criteria and patient-reported improvement, highlighting the need for better measurement tools. High response rates for lung involvement with certain novel drugs deserve further investigation.},
}

*Graft vs Host Disease/therapy
Humans
Chronic Disease
*Hematopoietic Stem Cell Transplantation/adverse effects
Treatment Outcome
Organ Specificity

@article {pmid39994463,
year = {2025},
author = {Banerjee, R and Fritz, AR and Akhtar, OS and Freeman, CL and Cowan, AJ and Shah, N and Landau, HJ and Kumar, SK and Vogl, DT and Efebera, YA and McCarthy, PL and Vesole, DH and Mendizabal, A and Krishnan, AY and Somlo, G and Stadtmauer, EA and Pasquini, MC},
title = {Urine-free response criteria predict progression-free survival in multiple myeloma: a post hoc analysis of BMT CTN 0702.},
journal = {Leukemia},
volume = {},
number = {},
pages = {},
pmid = {39994463},
issn = {1476-5551},
}

@article {pmid39992626,
year = {2025},
author = {Krishnamoorthy, GP and Glover, AR and Untch, BR and Sigcha-Coello, N and Xu, B and Vukel, D and Liu, Y and Tiedje, V and Pineda, JMB and Berman, K and Tamarapu, PP and Acuña-Ruiz, A and Saqcena, M and de Stanchina, E and Boucai, L and Ghossein, RA and Knauf, JA and Abdel-Wahab, O and Bradley, RK and Fagin, JA},
title = {RBM10 loss promotes metastases by aberrant splicing of cytoskeletal and extracellular matrix mRNAs.},
journal = {The Journal of experimental medicine},
volume = {222},
number = {5},
pages = {},
pmid = {39992626},
issn = {1540-9538},
support = {R01 CA50706-31/NH/NIH HHS/United States ; R01 CA255211/CA/NCI NIH HHS/United States ; RG183080//National Health and Medical Research Council/ ; //Marie-Josée and Henry R. Kravis Center for Molecular Oncology/ ; R01 CA050706/CA/NCI NIH HHS/United States ; P30 CA008748-58/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01 CA249663/CA/NCI NIH HHS/United States ; //Cycle for Survival/ ; //Royal Australasian College of Surgeons Foundation/ ; },
mesh = {Animals ; Humans ; Mice ; *Extracellular Matrix/metabolism ; *RNA-Binding Proteins/metabolism/genetics ; *rac1 GTP-Binding Protein/metabolism/genetics ; *Neoplasm Metastasis ; *Hyaluronan Receptors/metabolism/genetics ; *RNA, Messenger/genetics/metabolism ; Cytoskeleton/metabolism ; Thyroid Neoplasms/genetics/pathology/metabolism ; Cell Line, Tumor ; RNA Splicing/genetics ; Exons/genetics ; Alternative Splicing/genetics ; Gene Expression Regulation, Neoplastic ; Proto-Oncogene Proteins p21(ras)/genetics/metabolism ; Cell Movement/genetics ; },
abstract = {RBM10 modulates transcriptome-wide cassette exon splicing. Loss-of-function RBM10 mutations are enriched in thyroid cancers with distant metastases. Analysis of transcriptomes and genes mis-spliced by RBM10 loss showed pro-migratory and RHO/RAC signaling signatures. RBM10 loss increases cell velocity. Cytoskeletal and ECM transcripts subject to exon inclusion events included vinculin (VCL), tenascin C (TNC), and CD44. Knockdown of the VCL exon inclusion transcript in RBM10-null cells reduced cell velocity, whereas knockdown of TNC and CD44 exon inclusion isoforms reduced invasiveness. RAC1-GTP levels were increased in RBM10-null cells. Mouse HrasG12V/Rbm1OKO thyrocytes develop metastases that are reversed by RBM10 expression or by combined knockdown of VCL, CD44, and TNC inclusion isoforms. Thus, RBM10 loss generates exon inclusion in transcripts regulating ECM-cytoskeletal interactions, leading to RAC1 activation and metastatic competency. Moreover, a CRISPR-Cas9 screen for synthetic lethality with RBM10 loss identified NFκB effectors as central to viability, providing a therapeutic target for these lethal thyroid cancers.},
}

Animals
Humans
Mice
*Extracellular Matrix/metabolism
*RNA-Binding Proteins/metabolism/genetics
*rac1 GTP-Binding Protein/metabolism/genetics
*Neoplasm Metastasis
*Hyaluronan Receptors/metabolism/genetics
*RNA, Messenger/genetics/metabolism
Cytoskeleton/metabolism
Thyroid Neoplasms/genetics/pathology/metabolism
Cell Line, Tumor
RNA Splicing/genetics
Exons/genetics
Alternative Splicing/genetics
Gene Expression Regulation, Neoplastic
Proto-Oncogene Proteins p21(ras)/genetics/metabolism
Cell Movement/genetics

@article {pmid39991196,
year = {2025},
author = {Jefferson, JA and Chen, K and Hingorani, S and Malik, AB and Tykodi, SS and Keller, KH and Huang, Y and Smith, KD and Reed, RC and Weins, A and Akilesh, S},
title = {Genetic and Iatrogenic Defects in Peripheral Tolerance Associated with Anti-Nephrin Antibody-Associated Minimal Change Disease.},
journal = {Glomerular diseases},
volume = {5},
number = {1},
pages = {74-83},
pmid = {39991196},
issn = {2673-3633},
abstract = {INTRODUCTION: Minimal change disease (MCD) is a common cause of nephrotic syndrome in children and adults. Immune dysregulation is a contributor, but the relative roles of individual components of the immune system in MCD pathogenesis remain unclear.

CASE PRESENTATION: Here, we present 2 patients with defects in immune tolerance mechanisms that developed MCD associated with anti-nephrin antibodies. The first patient had a pathogenic deletion in FOXP3, leading to reduced regulatory T cells. Serum could not be obtained from this patient during the active phase of MCD to directly establish the presence of anti-nephrin antibodies. However, this patient demonstrated IgG dusting over podocyte cell bodies by immunofluorescence microscopy, as well as colocalization of IgG with nephrin in confocal microscopy. The second patient developed MCD in the context of immune checkpoint inhibitor treatment for metastatic carcinoma. Anti-nephrin antibodies were detected in this patient during active disease. The patient's kidney biopsy also showed evidence of binding of anti-nephrin antibodies within the glomeruli.

CONCLUSION: These cases demonstrate that genetic and iatrogenic mechanisms of breakdown in peripheral tolerance can lead to MCD.},
}

@article {pmid39990276,
year = {2025},
author = {Goel, U and Zanwar, S and Cowan, AJ and Banerjee, R and Khouri, J and Dima, D},
title = {Ciltacabtagene Autoleucel for the Treatment of Relapsed/Refractory Multiple Myeloma: Efficacy, Safety, and Place in Therapy.},
journal = {Cancer management and research},
volume = {17},
number = {},
pages = {357-372},
pmid = {39990276},
issn = {1179-1322},
abstract = {Idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) are two chimeric antigen receptor T cell (CAR T) therapies approved for use in patients with relapsed/refractory multiple myeloma (MM). Initially approved for late line MM (>4 prior lines), these were recently approved for use in MM with 1-2 prior lines of therapy in April 2024. As their use outside of the pivotal clinical trials continues to expand, it is important to critically evaluate the safety and efficacy of these therapies. Further, it is important to identify patients that would be most likely to benefit from the use of CAR T in earlier lines of therapy. Cilta-cel was initially studied in the phase-I LEGEND-2 study, followed by CARTITUDE-1 and CARTITUDE-4 trials, demonstrating remarkable efficacy. A recent large real-world study also demonstrated similar efficacy, in a mostly pivotal trial ineligible patient population. Based on these impressive results, cilta-cel is currently being studied in trials for newly diagnosed as well as smoldering multiple myeloma. Cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) are known toxicities of cilta-cel (and other CAR Ts), however movement and cognitive disorders (delayed neurotoxicity) and second primary malignancies are an evolving concern. In this article we discuss safety and efficacy data from existing cilta-cel studies. We propose that all patients with MM who have received ≥4 prior lines of therapy should be considered for CAR T. Earlier line use of CAR T should be restricted to patients with a high-risk disease phenotype (eg, functional high-risk disease). This disease phenotype has historically shown poor outcomes with standard triplet regimens and would be most likely to benefit from earlier use of CAR T: considering the availability of other safe and highly effective therapies, and potential high-risk toxicities of CAR T.},
}

@article {pmid39975072,
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 = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39975072},
issn = {2692-8205},
support = {R01 AI140891/AI/NIAID NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; S10 OD028685/OD/NIH HHS/United States ; S10 OD020069/OD/NIH HHS/United States ; U01 AI169385/AI/NIAID NIH HHS/United States ; },
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 glycosylation patterns, but other mutations have different effects on escape for unclear reasons. Overall, the extent that measurements of mutational effects on antibody neutralization can be generalized across HIV strains differs among antibodies.},
}

@article {pmid39974143,
year = {2025},
author = {Park, MS and Kumar, RD and Ovadiuc, C and Folta, A and McEwen, AE and Snyder, A and Fowler, DM and Rubin, AF and Shirts, BH and Starita, LM and Stergachis, AB},
title = {Insights on improving accessibility and usability of functional data to unlock its potential for variant interpretation.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {39974143},
support = {R01 HG013025/HG/NHGRI NIH HHS/United States ; UM1 HG011969/HG/NHGRI NIH HHS/United States ; },
abstract = {INTRODUCTION: Variant-level functional data is a core component of clinical variant classification and can aid in reinterpreting variants of uncertain significance (VUS). However, the usage of functional data by genetics professionals is currently unknown.

METHODS: An online survey was developed and distributed in spring of 2024 to individuals actively engaged in variant interpretation. Quantitative and qualitative methods were used to assess responses.

RESULTS: 190 eligible individuals responded, with 93% reporting interpreting 26 or more variants per year. The median respondent reported 11-20 years of experience. The most common professional roles were laboratory medical geneticists (23%) and variant review scientists (23%). 77% reported using functional data for variant interpretation in a clinical setting and overall respondents felt confident in assessing functional data. However, 67% indicated that functional data for variants of interest was rarely or never available, and 91% considered insufficient quality metrics or confidence in the accuracy of data as barriers to its use. 94% of respondents noted that better access to primary functional data and standardized interpretation of functional data would improve usage. Respondents also indicated that handling conflicting functional data is a common challenge in variant interpretation that is not performed in a systematic manner across institutions.

DISCUSSION: The results from this survey showed a demand for a comprehensive database with reliable quality metrics to support use of functional evidence in clinical variant interpretation. The results also highlight a need for guidelines regarding how putatively conflicting functional data should be used for variant classification.},
}

@article {pmid39990199,
year = {2025},
author = {Meehan, KA and Waters, AR and Wangen, M and Odebunmi, OO and Ferrari, RM and Marciniak, MW and Brenner, AT and Wheeler, SB and Shah, PD},
title = {Not just about pills: Findings from a national survey of pharmacists to understand their views on addressing social determinants of health.},
journal = {Preventive medicine reports},
volume = {51},
number = {},
pages = {102991},
pmid = {39990199},
issn = {2211-3355},
abstract = {OBJECTIVE: We evaluated community pharmacists' perspectives on addressing social determinants of health for their patients in the United States.

METHODS: From 9/2022-1/2023, we conducted a national, online survey of 578 pharmacists to evaluate their perspectives on social barriers affecting their patients, their pharmacy staff's ability to address these social barriers, and resources available or needed to address barriers.

RESULTS: Healthcare access and quality was perceived as the most addressable social barrier (59 %), while education (24 %) and neighborhood/built environment were perceived as the least addressable (14 %). Staff capacity to address social needs was significantly associated with increases in the pharmacy's ability to address social determinants of health across all five domains. Pharmacists were more likely to report adequate staff capacity if they practiced in independent community pharmacies.

CONCLUSIONS: Pharmacists commonly address social determinants of health of their patients, but most lack adequate staff capacity to address patient social barriers. Pharmacies with capacity can only address a portion of the social needs of their patient population. Greater access to resources and staffing support are needed to improve pharmacy's role in addressing patient unmet social needs.},
}

@article {pmid39989044,
year = {2025},
author = {Unger, JM and Mazza, GL and Elsaid, MI and Duan, F and Dressler, EV and Snavely, AC and Enserro, DM and Pugh, SL},
title = {When to adjust for multiplicity in cancer clinical trials.},
journal = {Journal of the National Cancer Institute. Monographs},
volume = {2025},
number = {68},
pages = {3-9},
pmid = {39989044},
issn = {1745-6614},
support = {UG1 CA189974/CA/NCI NIH HHS/United States ; //ECOG/ ; UG1CA189961//University of Rochester/ ; UG1 CA189823/CA/NCI NIH HHS/United States ; UG1CA189974/NH/NIH HHS/United States ; UG1CA189824//Wake Forest University/ ; UG1CA189961//Alliance NCORP Research Base/ ; U10 CA180794/CA/NCI NIH HHS/United States ; UG1CA189828//ACRIN/ ; U10 CA180819/CA/NCI NIH HHS/United States ; UG1CA189828//NRG Oncology/ ; 5UG1CA189955-11//Children's Oncology Group/ ; UG1 CA189867/CA/NCI NIH HHS/United States ; P30 CA016058-47S1//ACRIN/ ; UG1CA189974//SWOG/ ; UG1 CA189828/CA/NCI NIH HHS/United States ; UG1 CA189955/CA/NCI NIH HHS/United States ; UG1CA189823//SWOG Cancer Research Network/ ; U10CA180822//Wake Fores NCORP Research Base/ ; P30 CA016058/CA/NCI NIH HHS/United States ; UG1 CA189961/CA/NCI NIH HHS/United States ; UG1CA189867//NCI Community Oncology Research Program/ ; UG1 CA189824/CA/NCI NIH HHS/United States ; UG1CA189824//URCC NCORP Research Base/ ; },
mesh = {Humans ; *Neoplasms/therapy ; *Clinical Trials as Topic ; Research Design ; United States ; National Cancer Institute (U.S.) ; Data Interpretation, Statistical ; False Positive Reactions ; },
abstract = {Interpreting cancer clinical trial results often depends on addressing issues of multiplicity. When testing multiple hypotheses, unreliable findings can occur by chance due to the inflation of the type I error rate, the probability of mistakenly rejecting the null hypothesis when the null hypothesis is true. In this setting, researchers may often set the type I error rate (or the alpha level) low to limit false positive findings and the interpretation of a causal relationship where none exists. Conversely, overly conservative type I error control may result in declaring findings, that do not meet multiplicity-adjusted alpha levels, as false when they are actually true, reducing opportunities for new discovery. This presentation focuses on multiplicity adjustment in the context of clinical trials conducted within the NCI's Community Oncology Research Program (NCORP). Because federally sponsored trials often require long-term participation from patients and represent a substantial investment by taxpayers, striking the right balance between optimizing what is learned from these trials, while avoiding false positive results, should be a priority.},
}

Humans
*Neoplasms/therapy
*Clinical Trials as Topic
Research Design
United States
National Cancer Institute (U.S.)
Data Interpretation, Statistical
False Positive Reactions

@article {pmid39989043,
year = {2025},
author = {Mazza, GL and Culakova, E and Enserro, DM and Dignam, JJ and Unger, JM},
title = {Design and analysis considerations for investigating patient subgroups of interest within cancer clinical trials.},
journal = {Journal of the National Cancer Institute. Monographs},
volume = {2025},
number = {68},
pages = {22-29},
pmid = {39989043},
issn = {1745-6614},
support = {UG1CA189823/NH/NIH HHS/United States ; 5UG1CA189955-11//Children's Oncology Group/ ; //NCI Community Oncology Research Program/ ; UG1 CA189974/CA/NCI NIH HHS/United States ; //ECOG/ ; UG1CA189974//SWOG/ ; UG1CA189961//University of Rochester/ ; UG1 CA189823/CA/NCI NIH HHS/United States ; UG1 CA189961/CA/NCI NIH HHS/United States ; UG1 CA189824/CA/NCI NIH HHS/United States ; UG1CA189828//ACRIN/ ; U10 CA180822/CA/NCI NIH HHS/United States ; UG1 CA189828/CA/NCI NIH HHS/United States ; UG1 CA189955/CA/NCI NIH HHS/United States ; UG1CA189824//Wake Forest University/ ; UG1CA189867//NRG Oncology/ ; },
mesh = {Humans ; *Neoplasms/therapy ; *Clinical Trials as Topic ; *Research Design ; Precision Medicine/methods ; United States ; Patient Selection ; National Cancer Institute (U.S.) ; },
abstract = {Examining treatment effects in subgroups of patients defined by demographic, genetic, or clinical characteristics is increasingly of interest given the pursuit of personalized medicine and the importance of representation and equity in treatment decisions. The magnitude or even the direction of the treatment effect may vary across subgroups, and these differential treatment effects could have clinical implications. Subgroup analyses require caution in their interpretation, however, because of the high probability of a false-positive or false-negative conclusion. We outline study design and analysis considerations for responsibly investigating and reporting differential treatment effects across subgroups in oncology trials, with examples from the National Cancer Institute's National Clinical Trials Network and Community Oncology Research Program. Recommendations include ensuring appropriate representation of patients from subgroups of interest, recognizing power and multiplicity limitations, and treating exploratory subgroup analyses as hypothesis generating rather than practice changing.},
}

Humans
*Neoplasms/therapy
*Clinical Trials as Topic
*Research Design
Precision Medicine/methods
United States
Patient Selection
National Cancer Institute (U.S.)

@article {pmid39989038,
year = {2025},
author = {Bandos, H and Torres-Saavedra, PA and Culakova, E and Gunn, HJ and Lee, MK and Duan, F and Cecchini, RS and Unger, JM and Dueck, AC and Steingrimsson, JA},
title = {Best practices and pragmatic approaches for patient-reported outcomes and quality of life measures in cancer clinical trials.},
journal = {Journal of the National Cancer Institute. Monographs},
volume = {2025},
number = {68},
pages = {14-21},
pmid = {39989038},
issn = {1745-6614},
support = {5UG1CA189955-11//Children's Oncology Group/ ; //Community Oncology Research Program/ ; UG1 CA189974/CA/NCI NIH HHS/United States ; UG1CA189974//SWOG/ ; UG1CA189961//University of Rochester/ ; UG1 CA189823/CA/NCI NIH HHS/United States ; UG1 CA189824/CA/NCI NIH HHS/United States ; UG1CA189828//ACRIN/ ; U10 CA180819/CA/NCI NIH HHS/United States ; //ECOG/ ; U10CA180822/BC/NCI NIH HHS/United States ; UG1 CA189828/CA/NCI NIH HHS/United States ; UG1 CA189955/CA/NCI NIH HHS/United States ; UG1CA189824//Wake Forest University/ ; UG1CA189867//NRG Oncology/ ; /NH/NIH HHS/United States ; UG1 CA189961/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Quality of Life ; *Neoplasms/therapy/psychology ; *Patient Reported Outcome Measures ; *Clinical Trials as Topic ; Research Design ; },
abstract = {Patient-reported outcomes (PROs) are often collected in cancer clinical trials. Data obtained from trials with PROs are essential in evaluating participant experiences relating to symptoms, financial toxicity, or health-related quality of life. Although most features of clinical trial design, implementation, and analyses apply to trials with PROs, several considerations are unique. In this paper, we focus on specific issues such as selection of the tool, timing and frequency of assessments, and data collection methods. We discuss how the estimand framework can be used in connection with PROs, properties of common estimation methods, and handling of missing outcomes. With a plethora of literature available, we aim to summarize best practices and pragmatic approaches to the design and analysis of the studies incorporating PROs.},
}

Humans
*Quality of Life
*Neoplasms/therapy/psychology
*Patient Reported Outcome Measures
*Clinical Trials as Topic
Research Design

@article {pmid39989035,
year = {2025},
author = {Dressler, EV and Pugh, SL and Gunn, HJ and Unger, JM and Zahrieh, DM and Snavely, AC},
title = {Practical design considerations for cluster randomized controlled trials: lessons learned in community oncology research.},
journal = {Journal of the National Cancer Institute. Monographs},
volume = {2025},
number = {68},
pages = {56-64},
pmid = {39989035},
issn = {1745-6614},
support = {UG1 CA189974/CA/NCI NIH HHS/United States ; //ECOG/ ; R01CA207158/CA/NCI NIH HHS/United States ; UG1CA189824/CA/NCI NIH HHS/United States ; UG1CA189961//University of Rochester/ ; UG1 CA189823/CA/NCI NIH HHS/United States ; U10CA180822//Wake Forest NCORP/ ; //SWOG NCORP RB/ ; U10 CA180819/CA/NCI NIH HHS/United States ; 5UG1CA189955-11//Children's Oncology Group/ ; UG1 CA189867/CA/NCI NIH HHS/United States ; UG1 CA189828/CA/NCI NIH HHS/United States ; UG1 CA189955/CA/NCI NIH HHS/United States ; R01HS025194//Agency for Healthcare Research and Quality/ ; U10CA180882//NRG Oncology/ ; UG1CA189974//Alliance for Clinical Trials in Oncology/ ; UG1CA189824//Wake Forest University/ ; /NH/NIH HHS/United States ; UG1 CA189961/CA/NCI NIH HHS/United States ; UG1CA189867//NCI Community Oncology Research Program/ ; UG1 CA189824/CA/NCI NIH HHS/United States ; UG1CA189828//ACRIN/ ; R01 CA207158/CA/NCI NIH HHS/United States ; R01 HS025194/HS/AHRQ HHS/United States ; },
mesh = {Humans ; *Randomized Controlled Trials as Topic ; *Research Design ; *Medical Oncology/methods/standards ; *Neoplasms/therapy ; United States ; Cluster Analysis ; National Cancer Institute (U.S.) ; Sample Size ; Patient Selection ; },
abstract = {Cancer care delivery research trials conducted within the National Cancer Institute (NCI) Community Oncology Research Program (NCORP) routinely implement interventions at the practice or provider level, necessitating the use of cluster randomized controlled trials (cRCTs). The intervention delivery requires cluster-level randomization instead of participant-level, affecting sample size calculation and statistical analyses to incorporate correlation between participants within a practice. Practical challenges exist in the conduct of these cRCTs due to unique trial network infrastructures, including the possibility of unequal participant accrual totals and rates and staggered study initiation by clusters, potentially with differences between randomized arms. Execution of cRCT designs can be complex, ie, if some clusters do not accrue participants, unintended cluster-level crossover occurs, how best to identify appropriate cluster-level stratification, timing of randomization, and multilevel eligibility criteria considerations. This article shares lessons learned with potential mitigation strategies from 3 NCORP cRCTs.},
}

Humans
*Randomized Controlled Trials as Topic
*Research Design
*Medical Oncology/methods/standards
*Neoplasms/therapy
United States
Cluster Analysis
National Cancer Institute (U.S.)
Sample Size
Patient Selection

@article {pmid39988778,
year = {2025},
author = {Stamatatos, L},
title = {The Germline Targeting Vaccine Concept: Overview and Updates from HIV Pre-Clinical and Clinical Trials.},
journal = {Current HIV research},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570162X358302250206074255},
pmid = {39988778},
issn = {1873-4251},
abstract = {An effective HIV-1 vaccine should elicit diverse immune responses, including broadly neutralizing antibodies (bNAbs). Such antibodies recognize regions of the viral envelope glyco-protein (Env) that are conserved among the diverse HIV-1 clades and strains. They are isolated from people living with HIV-1 to protect animals from experimental viral exposure and reduce HIV-1 acquisition in clinical settings. However, despite efforts spanning several decades, bNAbs have not been elicited through immunization. The HIV Env efficiently binds bNAbs, but not their unmutated (germline, gl) precursors. In contrast, Env readily engages the germline precursors of antibodies with no, or very narrow, cross-neutralizing activities (non-neutralizing antibodies, nnAbs). That, in part, explains why Env-based immunogens consistently elicit nnAbs, but not bNAbs. In the past decade, Env-derived proteins have been specifically designed to engage the germline precursors of diverse bNAbs. These 'germline-targeting' Env immunogens activate the corresponding naive B cells in vivo, but are unable to guide their proper maturation towards their broadly neutralizing forms. For this, immunizations with currently not well-defined heterologous Envs are required. Here, we discuss the development of germline-targeting Env immunogens, their in vivo evaluation, and the strategies currently under evaluation that aim to rapidly guide the mat-uration of germline-precursor BCRs into their broadly neutralizing forms.},
}

@article {pmid39975340,
year = {2025},
author = {Jochim, BE and Topalidou, I and Lehrbach, NJ},
title = {Protein sequence editing defines distinct and overlapping functions of SKN-1A/Nrf1 and SKN-1C/Nrf2.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39975340},
issn = {2692-8205},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; P40 OD010440/OD/NIH HHS/United States ; R35 GM142728/GM/NIGMS NIH HHS/United States ; },
abstract = {The Nrf/NFE2L family of transcription factors regulates redox balance, xenobiotic detoxification, metabolism, proteostasis, and aging. Nrf1/NFE2L1 is primarily responsible for stress-responsive upregulation of proteasome subunit genes and is essential for adaptation to proteotoxic stress. Nrf2/NFE2L2 is mainly involved in activating oxidative stress responses and promoting xenobiotic detoxification. Nrf1 and Nrf2 contain very similar DNA binding domains and can drive similar transcriptional responses. In C. elegans, a single gene, skn-1, encodes distinct protein isoforms, SKN-1A and SKN-1C, that function analogously to mammalian Nrf1 and Nrf2, respectively, and share an identical DNA binding domain. Thus, the extent to which SKN-1A/Nrf1 and SKN-1C/Nrf2 functions are distinct or overlapping has been unclear. Regulation of the proteasome by SKN-1A/Nrf1 requires post-translational conversion of N-glycosylated asparagine residues to aspartate by the PNG-1/NGLY1 peptide:N-glycanase, a process we term 'sequence editing'. Here, we reveal the consequences of sequence editing for the transcriptomic output of activated SKN-1A. We confirm that activation of proteasome subunit genes is strictly dependent on sequence editing. In addition, we find that sequence edited SKN-1A can also activate genes linked to redox homeostasis and xenobiotic detoxification that are also regulated by SKN-1C, but the extent of these genes' activation is antagonized by sequence editing. Using mutant alleles that selectively inactivate either SKN-1A or SKN-1C, we show that both isoforms promote optimal oxidative stress resistance, acting as effectors for distinct signaling pathways. These findings suggest that sequence editing governs SKN-1/Nrf functions by tuning the SKN-1A/Nrf1 regulated transcriptome.},
}

@article {pmid39987960,
year = {2025},
author = {Ross, WL and Santiago-Rivera, Y and Tan, MT and Roy, MM and Bryant, S and Appel, BE and Casillas, J and Demedis, J and Smitherman, AB and Horwitz, LI and Hurtado-de-Mendoza, A and Mendoza, JA and Santacroce, SJ and Kadan-Lottick, NS},
title = {Design and methods of a multi-level intervention to improve adherence to childhood cancer survivorship care by partnering with primary care providers: The BRIDGES randomized controlled trial.},
journal = {Contemporary clinical trials},
volume = {},
number = {},
pages = {107859},
doi = {10.1016/j.cct.2025.107859},
pmid = {39987960},
issn = {1559-2030},
abstract = {BACKGROUND: Despite heightened risk of chronic health conditions, <20 % of childhood cancer survivors (CCS) receive guideline-recommended surveillance for late effects. Barriers include avoidance of reminders, lack of knowledge, and costs. The goal of the BRIDGES Study is to evaluate the effects of a multi-level, remote intervention on adherence to guideline-recommended surveillance among CCS by partnering with primary care providers (PCPs).

METHODS: This ongoing study is a multi-site, two-arm, prospective, parallel design, 1:1 randomized controlled non-inferiority trial (N = 240; n = 120/group). Eligibility criteria are: cancer diagnosis at age < 21 years, 2.0-4.0 years post-cancer therapy, and no previous specialty survivorship clinic care. The intervention includes: 1) patient survivorship education via telehealth with a cancer center nurse, including discussion of patient's individualized survivorship care plan (SCP), 2) ongoing patient-tailored health education within the electronic health record's patient portal, 3) a structured interactive phone call between the cancer center nurse and PCP, including discussion of patient's SCP, and 4) an in-person PCP visit for survivorship care. Patients randomized to the comparison group are contacted to schedule an in-person visit at their cancer center-based survivorship clinic. Adherence to guideline-recommended surveillance tests (primary outcome) is assessed at 1-year post-randomization (primary follow-up time point) and 2-years post-randomization (for durability). Patient knowledge, self-efficacy, and activation; PCP knowledge and self-efficacy; and process outcomes are also assessed.

CONCLUSION: Models of survivorship care that overcome existing barriers are needed. If efficacious, this scalable, remote intervention would be a valuable strategy to address barriers and bridge gaps in care to reach more CCS.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05448560.},
}

@article {pmid39986828,
year = {2025},
author = {Lange, PH and Schellhammer, PF},
title = {Tribute to Michael Droller MD.},
journal = {Urologic oncology},
volume = {43},
number = {2},
pages = {94},
doi = {10.1016/j.urolonc.2024.05.008},
pmid = {39986828},
issn = {1873-2496},
}

@article {pmid39985691,
year = {2025},
author = {Viskochil, RH and Lin, T and Gigic, B and Himbert, C and Bandera, VM and Skender, S and Holowatyj, AN and Schrotz-King, P and Steindorf, K and Strehli, I and Mutch, MG and Chao, D and Toriola, AT and Shibata, D and Siegel, EM and Li, CI and Hardikar, S and Peoples, AR and Figueiredo, JC and Schneider, M and Ulrich, CM and Ose, J},
title = {Sedentary behavior and physical activity one year after colorectal cancer diagnosis: results from the ColoCare Study.},
journal = {Journal of cancer survivorship : research and practice},
volume = {},
number = {},
pages = {},
pmid = {39985691},
issn = {1932-2267},
abstract = {PURPOSE: Physical activity plays key roles in colorectal cancer survivorship; however, the impact of different clinicodemographic outcomes on cross-sectional and longitudinal objectively measured physical activity 12 and 24 months post-diagnosis are unclear.

METHODS: ColoCare study participants (n = 165) wore an Actigraph GT3x accelerometer for 4-10 consecutive days to objectively assess activity levels 12 and 24 months after colorectal cancer diagnosis and resection. Associations between these clinical/demographic exposures and physical activity outcomes and longitudinal changes were determined using t-test, ANOVA F-test, and linear regression modeling, adjusting for common confounders (e.g., sex, age, stage).

RESULTS: Key physical activity and sedentary behavior variables significantly differed by demographic status, including minutes of weekly exercise by sex and age (age < 50: 364 min ± 303 min; age 50-70: 232 min ± 263 min; age > 70: 93 min ± 135 min, p < 0.001) and (%) daily sedentary time by age (age < 50: 64 ± 10%; age 50-70: 67 ± 7%; age > 70: 71 ± 7%, p = 0.003). Within the multivariate model, age was the primary measure consistently associated with activity differences. Participants who wore accelerometers 12- and 24-month post-resection (n = 52) significantly increased weekly exercise minutes (214 min ± 208 min vs. 288 min ± 316 min, p = 0.04).

CONCLUSION: Age is the primary clinicodemographic determinant separating physical activity levels in colorectal cancer survivors, and increases in exercise from 12 to 24 months are likely due to consolidation of sporadic daily physical activity into bouts of exercise.

Colorectal cancer survivors experience different volumes and changes in accelerometer-derived physical activity based on some (e.g., age) but not all (e.g., stage) clinicodemographic variables.},
}

@article {pmid39984572,
year = {2025},
author = {Ahmed, SR and Befano, B and Egemen, D and Rodriguez, AC and Desai, KT and Jeronimo, J and Ajenifuja, KO and Clark, C and Perkins, R and Campos, NG and Inturrisi, F and Wentzensen, N and Han, P and Guillen, D and Norman, J and Goldstein, AT and Madeleine, MM and Donastorg, Y and Schiffman, M and de Sanjose, S and Kalpathy-Cramer, J and , },
title = {Generalizable deep neural networks for image quality classification of cervical images.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {6312},
pmid = {39984572},
issn = {2045-2322},
mesh = {Humans ; Female ; *Uterine Cervical Neoplasms/diagnostic imaging/diagnosis/pathology ; *Neural Networks, Computer ; *Cervix Uteri/diagnostic imaging/pathology ; Image Processing, Computer-Assisted/methods ; Image Interpretation, Computer-Assisted/methods ; Deep Learning ; Artificial Intelligence ; },
abstract = {Successful translation of artificial intelligence (AI) models into clinical practice, across clinical domains, is frequently hindered by the lack of image quality control. Diagnostic models are often trained on images with no denotation of image quality in the training data; this, in turn, can lead to misclassifications by these models when implemented in the clinical setting. In the case of cervical images, quality classification is a crucial task to ensure accurate detection of precancerous lesions or cancer; this is true for both gynecologic-oncologists' (manual) and diagnostic AI models' (automated) predictions. Factors that impact the quality of a cervical image include but are not limited to blur, poor focus, poor light, noise, obscured view of the cervix due to mucus and/or blood, improper position, and over- and/or under-exposure. Utilizing a multi-level image quality ground truth denoted by providers, we generated an image quality classifier following a multi-stage model selection process that investigated several key design choices on a multi-heterogenous "SEED" dataset of 40,534 images. We subsequently validated the best model on an external dataset ("EXT"), comprising 1,340 images captured using a different device and acquired in different geographies from "SEED". We assessed the relative impact of various axes of data heterogeneity, including device, geography, and ground-truth rater on model performance. Our best performing model achieved an area under the receiver operating characteristics curve (AUROC) of 0.92 (low quality, LQ vs. rest) and 0.93 (high quality, HQ vs. rest), and a minimal total %extreme misclassification (%EM) of 2.8% on the internal validation set. Our model also generalized well externally, achieving corresponding AUROCs of 0.83 and 0.82, and %EM of 3.9% when tested out-of-the-box on the external validation ("EXT") set. Additionally, our model was geography agnostic with no meaningful difference in performance across geographies, did not exhibit catastrophic forgetting upon retraining with new data, and mimicked the overall/average ground truth rater behavior well. Our work represents one of the first efforts at generating and externally validating an image quality classifier across multiple axes of data heterogeneity to aid in visual diagnosis of cervical precancer and cancer. We hope that this will motivate the accompaniment of adequate guardrails for AI-based pipelines to account for image quality and generalizability concerns.},
}

Humans
Female
*Uterine Cervical Neoplasms/diagnostic imaging/diagnosis/pathology
*Neural Networks, Computer
*Cervix Uteri/diagnostic imaging/pathology
Image Processing, Computer-Assisted/methods
Image Interpretation, Computer-Assisted/methods
Deep Learning
Artificial Intelligence

@article {pmid39983446,
year = {2025},
author = {Ficarra, S and Kang, DW and Wilson, RL and Gonzalo-Encabo, P and Christopher, CN and Normann, AJ and Lopez, P and Lakićević, N and Dieli-Conwright, CM},
title = {Exercise medicine for individuals diagnosed with Lung Cancer: A systematic review and meta-analysis of health outcomes.},
journal = {Lung cancer (Amsterdam, Netherlands)},
volume = {201},
number = {},
pages = {108413},
doi = {10.1016/j.lungcan.2025.108413},
pmid = {39983446},
issn = {1872-8332},
abstract = {Consensus exists regarding the need to provide exercise interventions to individuals diagnosed with lung cancer (LC). Exercise interventions for this populations usually include multidisciplinary approaches, making the attempt to understand the effects of exercise a real challenge. Therefore, we designed a systematic review to identify the effects of exercise interventions among individuals with a LC diagnosis. Following the PRISMA guidelines, studies across 5 different databases were systematically screened. Eligible studies were randomised and non-randomised trials, including individuals with a LC diagnosis, administering exercise-only interventions. Three-level meta-analyses were performed for cardiorespiratory fitness, strength, physical function, anxiety, depression, and health-related quality of life. Differences between exercise types were also explored. The Cochrane Risk of Bias (RoB) II tool for randomised controlled trials and the RoB in non-randomised studies - of interventions were used to assess study quality. A total of 36,304 records were screened and 13 studies, including 547 LC survivors, were considered eligible. Randomised and non-randomised trials were mainly judged as "some concern" and at "serious" RoB, respectively. Meta-analyses reported significant improvements on physical function among exercise groups compared to control (ES = 0.62; 95 % CI: 0.10 to 1.15; p = 0.03), and no significant changes for all other variables. There is moderate evidence that exercise interventions appear to be an effective tool to improve physical function among individuals diagnosed with LC. Further studies are still needed to determine exercise prescription effectiveness on health outcomes, differences across exercise types and enhance individualized interventions.},
}

@article {pmid39982694,
year = {2025},
author = {Alduhayh, S and Laskar, RS and Jiang, X and Zhu, Z and Vincent, EE and Constantinescu, AE and Buchanan, DD and Grant, RC and Phipps, AI and Brenner, H and Huang, WY and Kweon, SS and Li, L and Pearlman, R and Castellví-Bel, S and Gruber, SB and Li, CI and Pellatt, A and Platz, EA and Van Guelpen, B and Zheng, W and Chan, AT and Figueiredo, JC and Ogino, S and Ulrich, CM and Gunter, MJ and Haycock, P and Severi, G and Murphy, N and Dimou, N},
title = {Association of genetic liability to allergic diseases with overall and early-onset colorectal cancer risk: a Mendelian randomization study.},
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-24-0970},
pmid = {39982694},
issn = {1538-7755},
abstract = {BACKGROUND: Tumor immunosurveillance theory supports that allergic conditions could decrease cancer risk. However, observational evidence yielded inconsistent results for the association between allergic diseases and colorectal cancer risk. We used Mendelian randomization (MR) to examine potential causal associations of allergies with risk of overall and early-onset colorectal cancer.

METHODS: Genome-wide association study summary statistic data were used to identify genetic variants associated with allergic diseases (Nvariants=65) and individual allergic conditions (asthma, hay fever/allergic rhinitis, eczema). Using two-sample MR, we examined these variants in relation to incident overall (Ncases=52,775 cases) and early-onset colorectal cancer (Ncases=6,176). The mediating role of white blood cells was examined using multivariable MR.

RESULTS: In inverse-variance weighted models, genetic liability to allergic diseases was inversely associated with overall (ORper log(odds)= 0.90 [95% CI= 0.85-0.96]; P< 0.01) and early-onset colorectal cancer (OR= 0.83 [95% CI= 0.73-0.95]; P= 0.01). Similar inverse associations were found for hay fever/allergic rhinitis or eczema, while no evidence of association was found between liability to asthma-related phenotypes and colorectal cancer risk. Multivariable MR adjustment for eosinophils weakened the inverse associations for liability to allergic diseases for overall (OR= 0.96 [95% CI= 0.89-1.03]; P= 0.26) and early-onset colorectal cancer (OR= 0.86 [95% CI= 0.73-1.01]; P= 0.06).

CONCLUSIONS: Our study supports a potential causal association between liability to allergic diseases, specifically hay fever/allergic rhinitis or eczema, and colorectal cancer, possibly at least in part mediated via eosinophil counts.

IMPACT: Our results provide evidence that allergic responses may also have a role in immunosurveillance against colorectal cancer.},
}

@article {pmid39982410,
year = {2025},
author = {Burfeind, KG and Funahashi, Y and Su, XT and Lackey, AE and Hagen, MW and Blanche, S and Emathinger, JM and Hebert, JF and McDonough, AA and Gurley, SB and Nelson, JW and Hutchens, MP},
title = {Kidney cell response to acute cardiorenal and isolated kidney ischemia-reperfusion injury.},
journal = {Physiological genomics},
volume = {},
number = {},
pages = {},
doi = {10.1152/physiolgenomics.00161.2024},
pmid = {39982410},
issn = {1531-2267},
support = {I01BX004288//U.S. Department of Veterans Affairs (VA)/ ; W81XWH2010196/PR191304//U.S. Department of Defense (DOD)/ ; 20CDA35320169//American Heart Association (AHA)/ ; K01DK121737//HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)/ ; //Collins Medical Trust (CMT)/ ; TL1TR002371//HHS | NIH | National Center for Advancing Translational Sciences (NCATS)/ ; KL2TR002370//HHS | NIH | National Center for Advancing Translational Sciences (NCATS)/ ; 24CDA1269598//American Heart Association (AHA)/ ; },
abstract = {Acute cardiorenal syndrome (CRS) represents a critical intersection of cardiac and renal dysfunction with profound clinical implications. Despite its significance, the molecular underpinnings that mediate cellular responses within the kidney during CRS remain inadequately understood. We employed single nucleus RNA sequencing (snRNAseq) to dissect the cellular transcriptomic landscape of the kidney following in a translational model of CRS, cardiac arrest/cardiopulmonary resuscitation (CA/PCR) in comparison to ischemia reperfusion injury (IRI). In each dataset, we found that proximal tubule (PT) cells of the kidney undergo significant gene expression changes, with decreased expression of genes critically important for cell identity and function, indicative of dedifferentiation. Based on this, we created a novel score to capture the dedifferentiation state of each kidney cell population and found that certain epithelial cell populations, such as the PT S1 and S2 segments, as well as the distal convoluted tubule, exhibited significant dedifferentiation response. Interestingly, the dedifferentiation response in the distal nephron differed in magnitude between IRI and CA/CPR. Gene set enrichment analysis (GSEA) of PT response to IRI and CA/CPR revealed similarities between the two models and key differences, including enrichment of immune system process genes. Transcriptional changes in both mouse models of AKI highly correlated with a dataset of human biopsies from patients diagnosed with acute kidney injury (AKI). This comprehensive single nucleus transcriptomic profiling provides valuable insights into the cellular mechanisms driving CRS.},
}

@article {pmid39981705,
year = {2025},
author = {Taylor, MR and Bradford, MC and Zhou, C and Fladeboe, KM and Wittig, JF and Baker, KS and Yi-Frazier, JP and Rosenberg, AR},
title = {Heart Rate Variability as a Digital Biomarker in Adolescents and Young Adults Receiving Hematopoietic Cell Transplantation.},
journal = {Cancer medicine},
volume = {14},
number = {4},
pages = {e70609},
pmid = {39981705},
issn = {2045-7634},
support = {//American Cancer Society/ ; },
mesh = {Humans ; Adolescent ; *Hematopoietic Stem Cell Transplantation ; *Heart Rate ; Male ; Female ; Young Adult ; *Quality of Life ; *Patient Reported Outcome Measures ; Anxiety ; Biomarkers ; Child ; Prospective Studies ; Depression ; Adult ; Autonomic Nervous System/physiopathology ; },
abstract = {INTRODUCTION: Adolescents and young adults (AYAs) receiving hematopoietic cell transplantation (HCT) are at high risk for poor psychosocial outcomes. Heart rate variability (HRV), a surrogate for autonomic nervous system activity, is a promising digital biomarker that has been linked to important outcomes. The objectives of this study were to prospectively describe the trajectory of HRV among AYAs receiving HCT and explore the association between HRV and patient-reported outcomes (PROs).

METHODS: This was a multi-site study embedded in a randomized trial among AYAs receiving HCT (NCT03640325). We collected sequential 24-h HRV metrics, including the standard deviation of normal-to-normal beats (SDNN), root-mean-square of successive differences (RMSSD), as well as frequency domain measures. PRO surveys queried anxiety, depression, quality of life, hope, and resilience at baseline and 3 months. We summarized outcomes using descriptive statistics, and Pearson correlation coefficients were used to examine the relationship between HRV and PROs.

RESULTS: Thirty-nine HRV recordings were collected from n = 16 participants aged 12-21 years. There was a moderately strong correlation between inferior baseline HRV and higher anxiety and depression (anxiety: r = -0.35 (p = 0.18) for SDNN, r = -0.47 (p = 0.07) for RMSSD; depression: r = -0.26 (p = 0.34) for SDNN, r = -0.39 (p = 0.14) for RMSSD). Among participants with elevated baseline anxiety, higher HRV suggested greater improvement in anxiety over time (r = -0.66 (p = 0.08) for SDNN, r = -0.31 (p = 0.45) for RMSSD).

CONCLUSIONS: There was a correlation between HRV and PROs in this study, and among those with elevated anxiety, HRV predicted improvement over time. Digital biomarkers may augment behavioral intervention design and implementation.},
}

Humans
Adolescent
*Hematopoietic Stem Cell Transplantation
*Heart Rate
Male
Female
Young Adult
*Quality of Life
*Patient Reported Outcome Measures
Anxiety
Biomarkers
Child
Prospective Studies
Depression
Adult
Autonomic Nervous System/physiopathology

@article {pmid39980037,
year = {2025},
author = {Nikolaienko, O and Anderson, GL and Chlebowski, RT and Jung, SY and Harris, HR and Knappskog, S and Lønning, PE},
title = {MGMT epimutations and risk of incident cancer of the colon, glioblastoma multiforme, and diffuse large B cell lymphomas.},
journal = {Clinical epigenetics},
volume = {17},
number = {1},
pages = {28},
pmid = {39980037},
issn = {1868-7083},
mesh = {Humans ; *Glioblastoma/genetics/epidemiology ; Female ; *Lymphoma, Large B-Cell, Diffuse/genetics/epidemiology ; *Tumor Suppressor Proteins/genetics ; *DNA Repair Enzymes/genetics ; *DNA Modification Methylases/genetics ; Case-Control Studies ; *DNA Methylation/genetics ; Aged ; Middle Aged ; *Promoter Regions, Genetic/genetics ; *Colonic Neoplasms/genetics/epidemiology ; Mutation ; Genetic Predisposition to Disease/genetics ; Epigenesis, Genetic/genetics ; Incidence ; },
abstract = {BACKGROUND: Constitutional BRCA1 epimutations (promoter hypermethylation) are associated with an elevated risk of triple-negative breast cancer and high-grade serous ovarian cancer. While MGMT epimutations are frequent in colon cancer, glioblastoma, and B-cell lymphoma, it remains unknown whether constitutional MGMT epimutations are associated with risk of any of these malignancies.

METHODS: We designed a nested case-control study, assessing potential associations between MGMT epimutations in blood from healthy individuals and subsequent risk of incident cancer. The study cohort was drawn from postmenopausal women, participating in the Women's Health Initiative (WHI) study, who had not been diagnosed with either colon cancer, glioblastoma, or B-cell lymphoma prior to study entry. The protocol included n = 400 women developing incident left-sided and n = 400 women developing right-sided colon cancer, n = 400 women developing diffuse large B-cell lymphomas, all matched on a 1:2 basis with cancer-free controls, and n = 195 women developing incident glioblastoma multiforme, matched on a 1:4 basis. All cancers were confirmed in centralized medical record review. Blood samples, collected at entry, were analyzed for MGMT epimutations by massive parallel sequencing. Associations between MGMT methylation and incident cancers were analyzed by Cox proportional hazards regression.

RESULTS: Analyzing epimutations affecting the key regulatory area of the MGMT promoter, the hazard ratio (HR) was 1.07 (95% CI 0.79-1.45) and 0.80 (0.59-1.08) for right- and left-sided colon cancer, respectively, 1.13 (0.78-1.64) for glioblastoma, and 1.11 (0.83-1.48) for diffuse large B-cell lymphomas. Sensitivity analyses limited to subregions of the MGMT promoter and to individuals with different genotypes of a functional SNP in the MGMT promoter (rs16906252), revealed no significant effect on HR for any of the cancer forms. Neither did we observe any effect of rs16906252 status on HR for any of the cancer forms among individuals methylated or non-methylated at the MGMT promoter.

CONCLUSIONS: Constitutional MGMT promoter methylation in normal tissue is not associated with an increased risk of developing colon cancer, glioblastoma, or B-cell lymphoma.},
}

Humans
*Glioblastoma/genetics/epidemiology
Female
*Lymphoma, Large B-Cell, Diffuse/genetics/epidemiology
*Tumor Suppressor Proteins/genetics
*DNA Repair Enzymes/genetics
*DNA Modification Methylases/genetics
Case-Control Studies
*DNA Methylation/genetics
Aged
Middle Aged
*Promoter Regions, Genetic/genetics
*Colonic Neoplasms/genetics/epidemiology
Mutation
Genetic Predisposition to Disease/genetics
Epigenesis, Genetic/genetics
Incidence

@article {pmid39979638,
year = {2025},
author = {Toghani, D and Gupte, S and Zeng, S and Mahammadov, E and Crosse, EI and Seyedhassantehrani, N and Burns, C and Gravano, D and Radtke, S and Kiem, HP and Rodriguez, S and Carlesso, N and Pradeep, A and Georgiades, A and Lucas, F and Wilson, NK and Kinston, SJ and Göttgens, B and Zong, L and Beerman, I and Park, B and Janssens, DH and Jones, D and Toghani, A and Nerlov, C and Pietras, EM and Mesnieres, M and Maes, C and Kumanogoh, A and Worzfeld, T and Cheong, JG and Josefowicz, SZ and Kharchenko, P and Scadden, DT and Scialdone, A and Spencer, JA and Silberstein, L},
title = {Author Correction: Niche-derived Semaphorin 4A safeguards functional identity of myeloid-biased hematopoietic stem cells.},
journal = {Nature aging},
volume = {},
number = {},
pages = {},
doi = {10.1038/s43587-025-00837-x},
pmid = {39979638},
issn = {2662-8465},
}

@article {pmid39979464,
year = {2025},
author = {Briney, CA and Henriksen, JC and Lin, C and Jones, LA and Benner, L and Rains, AB and Gutierrez, R and Gafken, PR and Rissland, OS},
title = {Muskelin is a substrate adaptor of the highly regulated Drosophila embryonic CTLH E3 ligase.},
journal = {EMBO reports},
volume = {},
number = {},
pages = {},
pmid = {39979464},
issn = {1469-3178},
support = {5T32GM136444//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; 5T32GM141742//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; R35GM128680//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; 2P40OD010949//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; CAREER 2056136//National Science Foundation (NSF)/ ; P30 CA015704/CA/NCI NIH HHS/United States ; S10 OD030225/CD/ODCDC CDC HHS/United States ; },
abstract = {The maternal-to-zygotic transition (MZT) is a conserved developmental process where the maternally-derived protein and mRNA cache is replaced with newly made zygotic gene products. We have previously shown that in Drosophila the deposited RNA-binding proteins ME31B, Cup, and Trailer Hitch are ubiquitylated by the CTLH E3 ligase and cleared. However, the organization and regulation of the CTLH complex remain poorly understood in flies because Drosophila lacks an identifiable substrate adaptor, and the mechanisms restricting the degradation of ME31B and its cofactors to the MZT are unknown. Here, we show that the developmental regulation of the CTLH complex is multi-pronged, including transcriptional control by OVO and autoinhibition of the E3 ligase. One major regulatory target is the subunit Muskelin, which we demonstrate is a substrate adaptor for the Drosophila CTLH complex. Finally, we find that Muskelin has few targets beyond the three known RNA-binding proteins, showing exquisite target specificity. Thus, multiple levels of integrated regulation restrict the activity of the embryonic CTLH complex to early embryogenesis, during which time it regulates three important RNA-binding proteins.},
}

@article {pmid38746305,
year = {2025},
author = {Ni, X and Richardson, RB and Godoy, AS and Ferla, MP and Kikawa, C and Scheen, J and Hannon, WW and Capkin, E and Lahav, N and Balcomb, BH and Marples, PG and Fairhead, M and Wang, S and Williams, EP and Tomlinson, CWE and Aschenbrenner, JC and Lithgo, RM and Winokan, M and Giroud, C and Chandran, AV and Walsh, M and Thompson, W and Bloom, JD and Barr, H and Kirkegaard, K and Koekemoer, L and Fearon, D and Evans, MJ and von Delft, F},
title = {Crystallographic fragment screening and deep mutational scanning of Zika virus NS2B-NS3 protease enable development of resistance-resilient inhibitors.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {38746305},
issn = {2692-8205},
support = {U19 AI171399/AI/NIAID NIH HHS/United States ; },
abstract = {The Zika viral protease NS2B-NS3 is essential for the cleavage of viral polyprotein precursor into individual structural and non-structural (NS) proteins and is therefore an attractive drug target. Generation of a robust crystal system of co-expressed NS2B-NS3 protease has enabled us to perform a crystallographic fragment screening campaign with 1076 fragments. 47 fragments with diverse scaffolds were identified to bind in the active site of the protease, with another 6 fragments observed in a potential allosteric site. To identify binding sites that are intolerant to mutation and thus suppress the outgrowth of viruses resistant to inhibitors developed from bound fragments, we performed deep mutational scanning of NS2B-NS3 protease. Merging fragment hits yields an extensive set of 'mergers', defined as synthetically accessible compounds that recapitulate constellations of observed fragment-protein interactions. In addition, the highly sociable fragment hits enable rapid exploration of chemical space via algorithmic calculation and thus yield diverse possible starting points that maximally explore the binding opportunities to NS2B-NS3 protease, facilitating its resistance-resilient antiviral development.},
}

@article {pmid39977705,
year = {2025},
author = {Boiko, JR and Ensbey, KS and Waltner, OG and Jenkins, IC and Bhise, SS and MacDonald, KP and Blazar, BR and Hall, AM and Gooley, TA and Minnie, SA and Lee, SJ and Furlan, SN and Hill, GR},
title = {Defining pathogenic IL-17 and CSF-1 gene expression signatures in chronic graft-versus-host disease.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2024025337},
pmid = {39977705},
issn = {1528-0020},
abstract = {Chronic graft-versus-host disease (cGVHD) remains the leading cause of non-relapse morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Effective therapeutics agents targeting dysregulated cytokines including IL-17 and CSF-1 have been defined in preclinical models of cGVHD, and efficacy in subsequent clinical trials has led to their recent FDA approval. Despite this, these agents are effective in only a subset of patients, expensive, difficult to access outside the US, and used in a trial-and-error fashion. The ability to readily discern druggable, dysregulated immunity in these patients is desperately needed to facilitate the selection of appropriate treatment and to potentially identify high-risk individuals for preemptive therapy. We used single cell sequencing-based approaches in our informative preclinical cGVHD models to "reverse engineer" temporal IL-17 and CSF-1 signatures in mouse blood that could be used to interrogate patients. We defined distinct, non-intuitive IL-17 and CSF-1 signatures in mouse blood monocytes that could be identified in relevant monocytes within 70% of patients at diagnosis of cGVHD and in half of patients at day +100 post-HCT who subsequently developed cGVHD. These signatures can now be evaluated prospectively in clinical studies to help delineate potential responder and non-responders to relevant therapeutics targeting these pathways.},
}

@article {pmid39976968,
year = {2025},
author = {Umoren, RA and Ezeaka, C and Berkelhamer, SK and Hippe, DS and Asangansi, IE and Cook, MW and Fajolu, IB and Olawuyi, O and Adeboboye, C and Ekhalufoh, OO and Fashola, OS and Feltner, J and Fisher, JD and James, JM and Imoukhuede, OM and Park, N and Quach, V and Stiffler, AK and Engmann, CM},
title = {Essential Newborn Care Virtual Simulations for Skills Retention in Newborn Care.},
journal = {JAMA network open},
volume = {8},
number = {2},
pages = {e2460565},
pmid = {39976968},
issn = {2574-3805},
mesh = {Humans ; Infant, Newborn ; Female ; *Clinical Competence/statistics & numerical data ; Nigeria ; *Simulation Training/methods ; Male ; Adult ; Infant Care/methods ; Cohort Studies ; Health Personnel/education ; },
abstract = {IMPORTANCE: Newborn mortality accounts for approximately 47% of all mortality of children under the age of 5 years. Virtual simulation may be a viable approach to support retention of essential newborn care knowledge and skills among health care professionals in low- and middle-income countries.

OBJECTIVE: To evaluate the association between mobile virtual simulation using Virtual Essential Newborn Care (vENC) and knowledge and skills retention in early newborn care in low-resource settings and to propose a frequency of virtual simulation use for among health care professionals who care for newborns in low-resource settings.

This cohort study was conducted at 23 primary, secondary, and tertiary health care facilities in Lagos, Nigeria, for 6 months between December 1, 2022, and June 30, 2023. Participants included nurses and midwives who participated in deliveries and provided newborn care. Potential participants who attended a Helping Babies Breathe or Essential Newborn Care (ENC) course within the past 1 year were excluded.

EXPOSURES: All participants received in-person training using the World Health Organization ENC 1 and ENC 2 curricula along with virtual simulation practice at variable recommended frequencies for 6 months after course completion.

MAIN OUTCOMES AND MEASURES: Primary outcomes included assessments of bag-valve-mask (BVM) ventilation skills, and performance on ENC 1 and ENC 2 case A and B scenarios conducted by trained research assistants before, immediately after, and 6 months after the in-person course. All scores ranged from 0% to 100%, with higher scores indicating better performance.

RESULTS: Of 70 enrolled participants (67 of 69 [97%] female), 62 (89%) completed the 6-month follow-up. Immediate posttraining performance (median [IQR] scores: BVM ventilation skills, 93% [86%-100%]; ENC 1 case scenario A, 72% [61%-78%]; ENC 1 case scenario B, 76% [68%-88%]; ENC 2 case scenario A, 80% [73%-87%]; and ENC 2 case scenario B, 88% [70%-95%]) improved compared with pretraining performance for all skill assessments (median [IQR] scores: BVM ventilation skills, 57% [29%-64%]; ENC 1 case scenario A, 39% [28%-50%]); ENC 2 case scenario A, 33% [20%-45%]) (all P < .001). There were further gains in performance at the 6-month follow-up assessment for BVM ventilation (median [IQR], 100% [86%-100%]; P = .04) and the ENC1 and ENC2 assessments by case scenario (case scenario A: ENC 1 median [IQR] score, 78% [72%-83%]; P = .001 and ENC 2 median [IQR] score, 87% [80%-93%]; P = .008; and case scenario B: ENC 1 median [IQR] score, 88% [76%-92%]; P = .009 and ENC 2 median [IQR] score, 93% [80%-100%]; P = .004) relative to the immediate postcourse assessment scores.

CONCLUSIONS AND RELEVANCE: Findings of this cohort study suggest that the app-based simulations may be effective in supporting the retention of knowledge and skills following ENC training and may contribute to further performance gains for health care professionals in low- and middle-income countries. More clinical and implementation research is needed to explore the impact of virtual simulations on health professionals' clinical practices and neonatal outcomes.},
}

Humans
Infant, Newborn
Female
*Clinical Competence/statistics & numerical data
Nigeria
*Simulation Training/methods
Male
Adult
Infant Care/methods
Cohort Studies
Health Personnel/education

@article {pmid39976936,
year = {2025},
author = {DeVine, A and Landier, W and Hudson, MM and Constine, LS and Bhatia, S and Armenian, SH and Gramatges, MM and Chow, EJ and Friedman, DN and Ehrhardt, MJ},
title = {The Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers: A Review.},
journal = {JAMA oncology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaoncol.2024.6812},
pmid = {39976936},
issn = {2374-2445},
abstract = {IMPORTANCE: Since 2003, the Children's Oncology Group (COG) has developed and disseminated the Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers. These guidelines have benchmarked the standard of care for long-term survivors of childhood cancer in North America and beyond. Since their inception, they have evolved in depth, scope, and contributors to maintain fidelity toward continually emerging evidence related to cancer survivorship. They are intended to inform care for individuals who survived 2 or more years from completion of childhood, adolescent, and young adult cancer-directed therapy and receiving care in either specialty or primary care environments. The guidelines are updated on a 5-year cycle, during which comprehensive literature searches pertaining to guideline-specific questions are performed, evidence abstracted from pertinent publications, and recommendations determined and scored following expert deliberation.

OBSERVATIONS: Version 6.0 of the guidelines, released in October 2023, comprised 165 sections and 45 health links and represents the cooperative efforts of 220 individuals. Major changes include the addition of recommendations regarding surveillance for genetic cancer predisposition, surveillance following the use of novel cancer treatment modalities, and routine vaccination practices during long-term follow-up. In addition, surveillance echocardiograms were omitted for those at low risk of cardiomyopathy.

CONCLUSIONS AND RELEVANCE: This narrative review outlines the historical evolution of the COG Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers, current methods guiding their development, and key recommendations from version 6.0. The guidelines are publicly available in their entirety online. The COG guidelines continue to set the standard for surveillance practices for long-term survivors of childhood, adolescent, and young adult cancer. The growing body of evidence supporting these recommendations will continue to guide their evolution to inform optimal survivorship care practices.},
}

@article {pmid39976415,
year = {2025},
author = {Dumm, W and Ralph, D and DeWitt, W and Vora, A and Araki, T and Victora, GD and Matsen Iv, FA},
title = {Leveraging DAGs to improve context-sensitive and abundance-aware tree estimation.},
journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences},
volume = {380},
number = {1919},
pages = {20230315},
doi = {10.1098/rstb.2023.0315},
pmid = {39976415},
issn = {1471-2970},
support = {/NH/NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; //James S. McDonnell Foundation/ ; /RI/ORIP NIH HHS/United States ; },
mesh = {*Phylogeny ; Models, Genetic ; Receptors, Antigen, B-Cell/genetics ; Software ; Likelihood Functions ; },
abstract = {The phylogenetic inference package GCtree uses abundance of sampled sequences to improve the performance of parsimony-based inference, using a branching process model. Our previous work showed that GCtree performs competitively on B-cell receptor data, compared with other similar tools. In this article, we describe recent enhancements to GCtree, including an efficient tree storage data structure that discovers additional diversity of parsimonious trees with negligible additional computational cost. We also describe a suite of new objective functions that can be used to rank these trees, including a Poisson context likelihood function that models sequence evolution in a context-sensitive way. We validate these additions to GCtree with simulated B-cell receptor data, and benchmark performance against other phylogenetic inference tools.This article is part of the theme issue '"A mathematical theory of evolution": phylogenetic models dating back 100 years'.},
}

*Phylogeny
Models, Genetic
Receptors, Antigen, B-Cell/genetics
Software
Likelihood Functions

@article {pmid39974149,
year = {2025},
author = {Bhardwaj, S and Galanter, N and Berenbrok, LA and Shah, PD and Bacci, JL},
title = {Pediatric vaccination in pharmacies is not associated with delayed well-child visits among commercially insured children.},
journal = {Health affairs scholar},
volume = {3},
number = {2},
pages = {qxaf028},
pmid = {39974149},
issn = {2976-5390},
abstract = {Pediatric vaccination rates in the United States lag national goals. Policies that expand pharmacy-based vaccinations among children could help improve vaccination rates. Opponents argue, however, that such policies will result in delayed or missed well-child visits as most children receive routine vaccinations in primary care settings. We evaluated the likelihood of having a timely well-child visit following a routine vaccination in pharmacies and primary care settings among children aged 4-17 years. We conducted a retrospective cohort analysis with commercial claims data from 2016-2019, using conditional logistic regression models. A timely well-child visit was defined as one within 12 months after a preceding well-child visit for primary analysis and 15 months for secondary analysis. Approximately 95% of the sample consisted of children with influenza among their index vaccine(s). The odds of having a timely well-child visit were similar between children who received vaccines in pharmacies and those who received them in primary care settings. Findings suggest that guardians or parents who choose pharmacy-based pediatric vaccinations for their commercially insured children do not forgo well-child visits and may actually be more likely to obtain a timely well-child visit. Extending pharmacy-based vaccinations to patients of all ages can help improve pediatric vaccination rates.},
}

@article {pmid39973814,
year = {2025},
author = {Landi, D and Navai, SA and Brock, RM and Fousek, K and Nawas, Z and Sanber, K and Chauvin-Fleurence, C and Bhat, RR and Xu, S and Krishnamurthy, P and Choe, M and Campbell, M and Morris, JS and Gad, AZ and Shree, A and Echeandia, A and Saadeldin, A and Matthew, PR and Mullikin, D and Bielamowicz, K and Kurenbekova, L and Major, AM and Salsman, VS and Byrd, TT and Hicks, MJ and Zhang, YJ and Yustein, J and Carisey, AF and Joseph, SK and Ahmed, N and Hegde, M},
title = {A checkpoint reversal receptor mediates bipartite activation and enhances CAR T-cell function.},
journal = {Cancer research communications},
volume = {},
number = {},
pages = {},
doi = {10.1158/2767-9764.CRC-24-0125},
pmid = {39973814},
issn = {2767-9764},
abstract = {The efficacy of CAR T-cells (CART) in solid tumors is limited by immune inhibition. In our study, we observed that effector cytokines mediated the upregulation of the PD-L1 immune-checkpoint in primary glioblastoma (GBM). To offset the PD-L1 inhibitory signal, we engineered PD-1 checkpoint reversal receptors (CPR) with a CD28 or 41BB co-stimulatory endodomain and co-expressed them with a first-generation or a CD28-containing second-generation HER2-specific CAR (CPR/CART) using bicistronic vectors. We found that bipartite T-cell activation, by CAR-generated signal 1 and CPR co-stimulation (signal 2), fine-tuned pro-inflammatory cytokine release and sustained antitumor activity. While both CPR28 and CPR41BB effectively counteracted the PD-1 signal in vitro, CPR41BB, when co-expressed with a first-generation CAR (CARζ/CPR41BB), promoted central memory differentiation following repeat antigenic stimulation. CARζ/CPR41BB T-cells formed a robust immune synapse with tumor targets, similar to a 4-1BB-containing second-generation CART, maintained the favorable metabolic parameters associated with 4-1BB co-stimulation, and demonstrated superior antitumor function after adoptive transfer in xenograft models of GBM and metastatic osteosarcoma. Thus, a CPR molecule with 4-1BB co-stimulation that curtails PD-1 inhibition and complements CAR signaling to optimize T-cell activation could enhance CART efficacy against solid tumors.},
}

@article {pmid39973220,
year = {2025},
author = {Meanley, S and Rodriguez Garcia, L and Lisha, NE and Ahmed, A and Korolkova, A and Figueroa, T and Nguyen, E and J Peluso, M and Cohn, LB and Deeks, S and Dubé, K and Sauceda, J},
title = {Exploring Stigma and Self-Image: Mixed-Methods Insights from HIV Cure-Related Research Participants Undergoing Analytical Treatment Interruptions.},
journal = {AIDS patient care and STDs},
volume = {},
number = {},
pages = {},
doi = {10.1089/apc.2024.0254},
pmid = {39973220},
issn = {1557-7449},
abstract = {This mixed-methods study explored self-image among people with HIV participating in an HIV cure-related study involving analytical treatment interruptions (ATIs). Using both quantitative and qualitative approaches, we described how self-image emerged across study participation, focusing on internalized stigma, emotional strengths, and the psychosocial dimensions of study participation. Data come from the SCOPE-ATI substudy (NCT00187512) of the University of California San Francisco SCOPE cohort (NCT04359186). Quantitative data were collected at three timepoints: pre-ATI (n = 15), post-ATI (n = 12), and end of the study (n = 14). We observed a general decline in self-image scores over time. However, participants maintained a moderately high agreement with statements about contributing to reducing HIV stigma through their involvement in the study. Qualitative interviews were collected pre-ATI (n = 11), during ATI (n = 8), and post-ATI (n = 6). Qualitative findings revealed two major themes shaping self-image: (1) experiencing and reconciling internalized HIV stigma and (2) self-evaluations in relation to life purpose. Many participants expressed disappointment at having to resume antiretroviral therapy, viewing it as a reminder of their HIV status and its associated stigma. Nevertheless, some found purpose and pride in their participation, motivated by altruistic contributions to improving future HIV control options. The findings highlight the emotional complexities of participating in HIV cure research and underscore the need for psychosocial support throughout ATI studies. While most participants experienced a decline in self-image, some derived meaning and empowerment from their involvement. This study suggests that addressing emotional well-being and reinforcing participants' contributions to science can enhance their experience in future research.},
}

@article {pmid39970314,
year = {2025},
author = {Theodore, DA and Neradilek, M and Gillespie, K and Edupuganti, S and Hinojosa, JC and Lama, JR and De La Grecca, R and Wu, YH and Davis, A and Mangini, D and Andrew, P and Marovich, MA and Zwerski, S and Broder, G and Andrasik, MP and Castor, D and Roxby, AC and Cohen, M and Huang, Y and Karuna, ST and Sobieszczyk, ME},
title = {Brief Report: Associations Between Gender and Solicited Adverse Events After Passive Infusion of VRC01 or Placebo in HVTN 704/HPTN 085.},
journal = {Journal of acquired immune deficiency syndromes (1999)},
volume = {98},
number = {4},
pages = {340-345},
doi = {10.1097/QAI.0000000000003582},
pmid = {39970314},
issn = {1944-7884},
support = {//HIV Vaccine Trials Network/ ; },
mesh = {Humans ; Male ; Female ; *HIV Infections/drug therapy ; Adult ; *Broadly Neutralizing Antibodies/therapeutic use/administration & dosage ; Transgender Persons ; Peru ; Young Adult ; Brazil ; Sexual and Gender Minorities ; Sex Factors ; Middle Aged ; United States ; Adolescent ; Antibodies, Monoclonal ; HIV Antibodies ; },
abstract = {BACKGROUND: Realizing the potential of HIV prevention options requires understanding product tolerability across diverse groups vulnerable to HIV acquisition. Gender minority (GM) individuals are understudied in clinical trials.

SETTING: HVTN 704/HIV Prevention Trials Network 085, a phase 2b randomized HIV prevention trial, enrolled MSM and transgender participants from Brazil, Peru, Switzerland, and the United States to receive an infusion every 8 weeks (10 total) of VRC01 30 mg/kg, VRC01 10 mg/kg, or placebo. Solicited adverse events (AEs) were recorded for 3 days after each infusion.

METHODS: Gender was defined by self-report and sex assigned-at-birth. Multivariate mixed logistic models were used to estimate the association between gender (cisgender men [CM] vs. GM participants [transgender women, transgender men, or another gender]) and solicited AE frequency and severity.

RESULTS: GM participants reported more solicited AEs than CM among all participants (adjusted OR 1.59, 95% CI: 1.20 to 2.10, P = 0.001) and among placebo recipients (1.72, 1.05 to 2.81, P = 0.031). The severity of solicited AEs (occurrence of grade 2 and higher event) did not significantly differ overall (1.83, 0.79 to 4.20, P = 0.174) or among placebo recipients (3.05, 0.76 to 12.32, P = 0.112). Grade 2 events were reported after 1% and 2% of total infusions among CM and GM participants, respectively. Grade 3-4 events were rare overall (<0.1%). Completion of 10 infusions was high (78.6%) and slightly higher in CM (79.2%) than GM participants (73%).

CONCLUSIONS: This is the first report of associations between gender and solicited AEs after monoclonal antibody infusion. GM participants reported more events; severity was low. HIV prevention trials must engage and support GM individuals to best evaluate tolerability of novel agents.},
}

Humans
Male
Female
*HIV Infections/drug therapy
Adult
*Broadly Neutralizing Antibodies/therapeutic use/administration & dosage
Transgender Persons
Peru
Young Adult
Brazil
Sexual and Gender Minorities
Sex Factors
Middle Aged
United States
Adolescent
Antibodies, Monoclonal
HIV Antibodies

@article {pmid39970310,
year = {2025},
author = {Sommers, J and Dizon, DS and Lewis, MA and Stone, E and Andreoli, R and Henderson, V},
title = {Assessing health information seeking behaviors among targeted social media users using an infotainment video about a cancer clinical trial: a Population-based Descriptive Study.},
journal = {JMIR cancer},
volume = {},
number = {},
pages = {},
doi = {10.2196/56098},
pmid = {39970310},
issn = {2369-1999},
abstract = {BACKGROUND: Lack of information, awareness, and misconceptions about clinical trials are major barriers to cancer clinical trial participation. Digital and social media are dominant sources of health information and offer optimal opportunities to improve public medical awareness and education by providing accurate and trust-worthy sources of health information from reliable sources. Infotainment, material intended to both entertain and inform, is an effective strategy for engaging and educating audiences that can be easily disseminated using social media and may be a novel way to improve awareness of and recruitment in clinical trials.

OBJECTIVE: The purpose of this study was to evaluate whether an infotainment video promoting a clinical trial, disseminated using social media, could drive health information seeking behaviors.

METHODS: As part of a video series, we created an infotainment video focused on promotion of a specific cancer clinical trial. We instituted a dissemination and marketing process on Facebook to measure video engagement and health information seeking behaviors among targeted audiences who expressed interest in breast cancer research and organizations. To evaluate video engagement, we measured reach, retention, outbound clicks, and outbound click-through rate. Frequencies and descriptive statistics were used to summarize each measure.

RESULTS: The video substantially increased health information seeking behavior by increasing viewership from 1 visitor one month prior to launch to 414 outbound clicks from the video to the clinical trial webpage during the 21-day social media campaign period.

CONCLUSIONS: Our study shows that digital and social media tools can be tailored for specific target audiences, are scalable, and can be disseminated at low cost, making it an accessible educational, recruitment, and retention strategy focused on improving awareness of clinical trials.

CLINICALTRIAL: ClinicalTrials.gov NCT03418961.},
}

@article {pmid39896663,
year = {2025},
author = {Dadonaite, B and Burrell, AR and Logue, J and Chu, HY and Payne, DC and Haslam, DB and Staat, MA and Bloom, JD},
title = {SARS-CoV-2 neutralizing antibody specificities differ dramatically between recently infected infants and immune-imprinted individuals.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39896663},
issn = {2692-8205},
abstract = {The immune response to viral infection is shaped by past exposures to related virus strains, a phenomenon known as imprinting. For SARS-CoV-2, much of the population has been imprinted by a viral spike from an early strain, either through vaccination or infection during the early stages of the COVID-19 pandemic. As a consequence of this imprinting, infection with more recent SARS-CoV-2 strains primarily boosts cross-reactive antibodies elicited by the imprinting strain. Here we compare the neutralizing antibody specificities of imprinted individuals versus infants infected with a recent strain. Specifically, we use pseudovirus-based deep mutational scanning to measure how spike mutations affect neutralization by the serum antibodies of adults and children imprinted by the original vaccine versus infants with a primary infection by a XBB* variant. While the serum neutralizing activity of the imprinted individuals primarily targets the spike receptor-binding domain (RBD), serum neutralizing activity of infants only infected with XBB* mostly targets the spike N-terminal domain (NTD). In these infants, secondary exposure to the XBB* spike via vaccination shifts more of the neutralizing activity towards the RBD, although the specific RBD sites targeted are different than for imprinted adults. The dramatic differences in neutralization specificities among individuals with different exposure histories likely impact SARS-CoV-2 evolution.},
}

@article {pmid39896535,
year = {2025},
author = {Verwimp, S and Wagoner, J and Arenas, EG and De Coninck, L and Abdelnabi, R and Hyde, JL and Schiffer, JT and White, JM and Matthijnssens, J and Neyts, J and Polyak, SJ and Delang, L},
title = {Combinations of approved oral nucleoside analogues confer potent suppression of alphaviruses in vitro and in vivo.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39896535},
issn = {2692-8205},
abstract = {Alphaviruses such as chikungunya virus (CHIKV) pose a significant threat to global health, yet specific antiviral therapies remain unavailable. In this study, we evaluated combinations of three approved oral directly acting antiviral (DAA) drugs (sofosbuvir (SOF), molnupiravir (MPV) and favipiravir (FAV)) against CHIKV, Semliki Forest virus (SFV), Sindbis virus (SINV), and Venezuelan Equine Encephalitis virus (VEEV) in vitro and in vivo. In human skin fibroblasts, synergistic antiviral effects were observed for the drug combinations MPV + SOF and FAV + SOF against CHIKV, and for FAV + SOF against SFV. In human liver Huh7 cells, the combinations of FAV + MPV conferred additive to synergistic activity against VEEV and SINV strains, while SOF synergized with FAV against SINV strains. In a mouse model of CHIKV arthritis, MPV improved CHIKV-induced foot swelling and reduced systemic infectious virus titers. Combination treatment with suboptimal doses of MPV and SOF significantly reduced foot swelling and decreased infectious virus titers in serum as compared to single doses of each drug. Sequencing of CHIKV RNA from mouse joint tissue revealed that MPV caused dose-dependent increases in mutations in the CHIKV genome. Upon combination therapy of MPV with SOF, the number of mutations was significantly lower compared to single treatment with several higher doses of MPV. In summary, combining approved oral nucleoside analogs confers potent suppression of multiple alphaviruses in vitro and in vivo with enhanced control of viral genetic evolution in the face of antiviral drug pressure. These drug combinations may ultimately lead to the development of potent combinations of pan-family alphavirus inhibitors.},
}

@article {pmid39868184,
year = {2025},
author = {Gen, R and Addetia, A and Asarnow, D and Park, YJ and Quispe, J and Chan, MC and Brown, JT and Lee, J and Campbell, MG and Lapointe, CP and Veesler, D},
title = {SARS-CoV-2 nsp1 mediates broad inhibition of translation in mammals.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {39868184},
issn = {2692-8205},
abstract = {SARS-CoV-2 nonstructural protein 1 (nsp1) promotes innate immune evasion by inhibiting host translation in human cells. However, the role of nsp1 in other host species remains elusive, especially in bats which are natural reservoirs of sarbecoviruses and possess a markedly different innate immune system than humans. Here, we reveal that SARS-CoV-2 nsp1 potently inhibits translation in bat cells from Rhinolophus lepidus, belonging to the same genus as known sarbecovirus reservoirs hosts. We determined a cryo-electron microscopy structure of SARS-CoV-2 nsp1 bound to the Rhinolophus lepidus 40S ribosome and show that it blocks the mRNA entry channel via targeting a highly conserved site among mammals. Accordingly, we found that nsp1 blocked protein translation in mammalian cell lines from several species, underscoring its broadly inhibitory activity and conserved role in numerous SARS-CoV-2 hosts. Our findings illuminate the arms race between coronaviruses and mammalian host immunity (including bats), providing a foundation for understanding the determinants of viral maintenance in bat hosts and spillovers.},
}

@article {pmid39969870,
year = {2025},
author = {Chen, J and Raymundo, C and Martinez, A and Lee, SJ and Stevenson, PA and Shinohara, MM},
title = {Histopathologic Grading of Acute Cutaneous Graft-vs-Host Disease and Nonrelapse Mortality.},
journal = {JAMA dermatology},
volume = {},
number = {},
pages = {},
pmid = {39969870},
issn = {2168-6084},
}

@article {pmid39969427,
year = {2025},
author = {Levy, C and Naik, H and Overbey, J and Hedstrom, K and Wang, K and McDonough, C and Freeman, M and Keel, SB and Erwin, AL and Dickey, AK and Leaf, RK and Quigley, J and Mazepa, M and Wang, B and Phillips, J and Parker, C and McGuire, B and Kazamel, M and Bonkovsky, H and Rudnick, S and Anderson, KE and Moghe, A and Thapar, M and Saberi, B and Wheeden, K and Desnick, R and Balwani, M and , },
title = {Liver involvement in a large cohort of patients with erythropoietic protoporphyria or X-linked protoporphyria.},
journal = {Hepatology communications},
volume = {9},
number = {3},
pages = {},
pmid = {39969427},
issn = {2471-254X},
mesh = {Humans ; Female ; *Protoporphyria, Erythropoietic/complications ; Male ; Adult ; Middle Aged ; *Liver/pathology ; Young Adult ; Adolescent ; Protoporphyrins/blood ; Genetic Diseases, X-Linked/complications ; Liver Diseases/etiology ; Child ; Longitudinal Studies ; Aged ; 5-Aminolevulinate Synthetase/deficiency ; },
abstract = {BACKGROUND: Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are characterized by the accumulation of protoporphyrin in the marrow, erythrocytes, plasma, skin, and liver, and present clinically with painful cutaneous phototoxicity. Liver abnormalities have been reported in over 25% of patients with EPP. Further characterization of liver involvement in protoporphyria is needed.

METHODS: Patients with EPP or XLP enrolled in the longitudinal studies of the NIH-supported Porphyrias Consortium were included. Medical history, laboratory, and liver histology data were abstracted and described.

RESULTS: A total of 322 patients were enrolled; 28 (8.7%) had XLP, 52% were female, and the median age at enrollment was 33.3 years. Liver chemistries were available for 235 patients, and 132 (56.2%) had abnormalities, mostly mild. Abnormal liver enzymes were associated with higher erythrocyte protoporphyrin levels. Eleven patients had advanced protoporphyric hepatopathy. In total, 54 (16.8%) underwent cholecystectomy, 8 (2.5%) had a liver transplant, 4 (1.2%) had a bone marrow transplant, and 8 (2.5%) died. At least 4 deaths were caused by liver failure due to protoporphyric hepatopathy, 2 were complications of bone marrow transplant, and 1 from HCC, which developed in a patient with EPP without cirrhosis. Patients with XLP were more likely to develop liver-related complications compared to EPP.

CONCLUSIONS: Liver abnormalities are common in patients with EPP and XLP. In this national registry, only 3.4% had protoporphyric hepatopathy, with most requiring a transplant. Of the deaths, 62.5% were attributable to liver disease. Further observations are needed for guiding hepatic evaluation and management of patients with protoporphyria with or without initial hepatic abnormalities.},
}

Humans
Female
*Protoporphyria, Erythropoietic/complications
Male
Adult
Middle Aged
*Liver/pathology
Young Adult
Adolescent
Protoporphyrins/blood
Genetic Diseases, X-Linked/complications
Liver Diseases/etiology
Child
Longitudinal Studies
Aged
5-Aminolevulinate Synthetase/deficiency

@article {pmid39969207,
year = {2025},
author = {Mehta, RS and Lee, SJ and Gooley, TA and Thur, L and Dahlberg, A and Delaney, C and Gyurkocza, B and Vo, PT and Deeg, HJ and Milano, F},
title = {Long-Term Outcomes and Quality of Life with Treosulfan-Based Conditioning in Hematological Malignancies.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2024015392},
pmid = {39969207},
issn = {2473-9537},
}

@article {pmid39966732,
year = {2025},
author = {Chawana, TD and Walsh, SR and Stranix-Chibanda, L and Chirenje, ZM and Yu, C and Zhang, L and Seaton, KE and Heptinstall, J and Zhang, L and Paez, CA and Gamble, T and Karuna, ST and Andrew, P and Hanscom, B and Sobieszczyk, ME and Edupuganti, S and Gay, CL and Mannheimer, SB and Hurt, CB and Stephenson, KE and Polakowski, LL and Spiegel, H and Yacovone, M and Regenold, S and Yen, C and Baumblatt, JA and Gama, L and Barouch, DH and Piwowar-Manning, E and Koup, RA and Tomaras, GD and Hyrien, O and Roxby, AC and Huang, Y and , },
title = {Pharmacokinetic interaction assessment of an HIV broadly neutralizing monoclonal antibody VRC07-523LS: a cross-protocol analysis of three phase 1 trials in people without HIV.},
journal = {BMC immunology},
volume = {26},
number = {1},
pages = {8},
pmid = {39966732},
issn = {1471-2172},
support = {UM1 AI068614/AI/NIAID NIH HHS/United States ; },
mesh = {Humans ; Adult ; *HIV Antibodies/immunology ; Female ; Male ; *Antibodies, Monoclonal/pharmacokinetics ; *HIV Infections/drug therapy/immunology ; Middle Aged ; Broadly Neutralizing Antibodies ; HIV-1/immunology ; Antibodies, Neutralizing/immunology ; Young Adult ; },
abstract = {VRC07-523LS is a safe and well-tolerated monoclonal antibody (mAb) targeting the CD4 binding site on the HIV envelope (Env) trimer. Efficacy of VRC07-523LS, in combination with mAbs targeting other HIV epitopes, will be evaluated in upcoming trials to prevent HIV acquisition in adults. However, differences in the pharmacokinetics (PK) of VRC07-523LS when administered alone vs. in combination with other mAbs have not been formally assessed. We performed a cross-protocol analysis of three clinical trials and included data from a total of 146 adults without HIV who received intravenous (n = 95) or subcutaneous (n = 51) VRC07-523LS, either alone ('single'; n = 100) or in combination with 1 or 2 other mAbs ('combined'; n = 46). We used an open, two-compartment population PK model to describe serum concentrations of VRC07-523LS over time, accounting for inter-individual variabilities. We compared individual-level PK parameters between the combined vs. single groups using the targeted maximum likelihood estimation method to adjust for participant characteristics. No significant differences were observed in clearance rate, inter-compartmental clearance, distribution half-life, or total VRC07-523LS exposure over time. However, for the combined group, mean central volume of distribution, peripheral volume of distribution, and elimination half-life were slightly greater, corresponding to slightly lower predicted concentrations early post-administration with high levels being maintained in both groups. These results suggest potential PK interactions between VRC07-523LS and other mAbs, but with small clinical impact in the context of HIV prevention. Our findings support coadministration of VRC07-523LS with other mAbs, and the use of the developed PK models to design future trials for HIV prevention.},
}

Humans
Adult
*HIV Antibodies/immunology
Female
Male
*Antibodies, Monoclonal/pharmacokinetics
*HIV Infections/drug therapy/immunology
Middle Aged
Broadly Neutralizing Antibodies
HIV-1/immunology
Antibodies, Neutralizing/immunology
Young Adult

@article {pmid39966627,
year = {2025},
author = {Bock, TJ and Colonne, CK and Fiorenza, S and Turtle, CJ},
title = {Outcome correlates of approved CD19-targeted CAR T cells for large B cell lymphoma.},
journal = {Nature reviews. Clinical oncology},
volume = {},
number = {},
pages = {},
pmid = {39966627},
issn = {1759-4782},
abstract = {CD19-targeted chimeric antigen receptor (CAR) T cells have provided a breakthrough in the treatment of patients with relapsed and/or refractory large B cell lymphoma (LBCL). Currently, three CD19-targeted CAR T cell products are approved by the FDA and various other regulators for the treatment of patients with LBCL: axicabtagene ciloleucel, tisagenlecleucel and lisocabtagene maraleucel. Response rates following infusion of these CD19-targeted CAR T cells have been promising; however, approximately half of treated patients show relapse within 2 years. Furthermore, receiving these agents can be associated with serious toxicities, including cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. In this Review, we summarize the factors associated with the efficacy, including response and survival outcomes, and toxicity of CD19-targeted CAR T cells in pivotal clinical trials and large real-world datasets describing the outcomes of patients with LBCL who received treatment with these products.},
}

@article {pmid39965886,
year = {2025},
author = {Attygalle, AD and Karube, K and Jeon, YK and Cheuk, W and Bhagat, G and Chan, JKC and Naresh, KN},
title = {The fifth edition of the WHO classification of mature T cell, NK cell and stroma-derived neoplasms.},
journal = {Journal of clinical pathology},
volume = {},
number = {},
pages = {},
doi = {10.1136/jcp-2025-210074},
pmid = {39965886},
issn = {1472-4146},
abstract = {The fifth edition of the WHO Classification of Haematolymphoid Tumors (WHO-HAEM5) introduces significant advancements in the understanding and diagnosis of mature T cell and NK cell, and stroma-derived neoplasms, and incorporates molecular and genetic data/findings accrued over the past years. The classification has been reorganised using a hierarchical system, employed across the fifth edition of the WHO classification of tumours of all organ systems. This review highlights recent developments, evolving concepts, and key updates since the revised fourth edition (WHO-HAEM4R). It enumerates the minimal/essential criteria necessary for diagnosis and classification, constituting not only the importance of clonality analysis in the workup of certain T cell neoplasms and the detection of infectious agents and specific genetic alterations in a subset of entities but also the applicability of these criteria in resource-constrained settings. 'Stroma-derived neoplasms of lymphoid tissues discussed in this review is a new category introduced in HAEM5 that encompasses mesenchymal tumours occurring exclusively in lymph nodes and spleen and mesenchymal dendritic cell neoplasms previously classified as 'histiocytic/dendritic cell neoplasms'.},
}

@article {pmid39965175,
year = {2025},
author = {Hansen, DK and Peres, LC and Dima, D and Richards, A and Shune, L and Afrough, A and Midha, S and Dhakal, B and Kocoglu, MH and Atrash, S and Ferreri, C and Castaneda, O and Davis, JA and Bhurtel, E and McGuirk, J and Wagner, C and Bansal, R and Costello, P and Smith, K and Lieberman-Cribbin, A and De Avila, G and Purvey, S and Hosoya, H and Mikkilineni, L and Oswald, LB and Kaur, G and Pasvolsky, O and Gaballa, M and Herr, MM and Forsberg, P and Janakiram, M and Htut, M and Asoori Maringanti, S and Kalariya, N and Hashmi, H and Reshef, R and Sborov, DW and Nadeem, O and Anwer, F and Khouri, J and Raza, S and Atanackovic, D and Alsina, M and Freeman, CL and Locke, FL and Voorhees, P and Anderson, LD and Richard, S and Martin, T and Lin, Y and Patel, KK and Sidana, S and , },
title = {Comparison of Standard-of-Care Idecabtagene Vicleucel and Ciltacabtagene Autoleucel in Relapsed/Refractory Multiple Myeloma.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2401730},
doi = {10.1200/JCO-24-01730},
pmid = {39965175},
issn = {1527-7755},
abstract = {PURPOSE: Idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), two B-cell maturation antigen-directed chimeric antigen receptor (CAR) T-cell therapies have demonstrated remarkable efficacy in relapsed/refractory multiple myeloma (RRMM). We compare safety, efficacy, and survival among patients with RRMM treated with standard-of-care (SOC) ide-cel or cilta-cel.

METHODS: Data were from a retrospective chart review of patients with RRMM leukapheresed by December 31, 2022, with the intent to receive SOC ide-cel or cilta-cel at 19 institutions. An inverse probability of treatment weighting (IPTW) approach was used to compare outcomes by therapy type.

RESULTS: A total of 641 patients were leukapheresed by December 31, 2022, with ide-cel (n = 386) and cilta-cel (n = 255). Five hundred eighty-six patients were infused (n = 350 for ide-cel; n = 236 for cilta-cel) with a median follow-up of 12.6 and 13.0 months for ide-cel and cilta-cel, respectively. After IPTW, patient characteristics were well balanced. Cilta-cel was associated with higher likelihood of grade ≥3 cytokine release syndrome (CRS; odds ratio [OR], 6.80 [95% CI, 2.28 to 20.33]), infections (OR, 2.03 [95% CI, 1.41 to 2.92]), second primary malignancies (OR, 1.77 [95% CI, 0.89 to 3.56]), and delayed neurotoxicity (OR, 20.07 [95% CI, 4.46 to 90.20]). Cilta-cel was also associated with better treatment responses (≥complete response: OR, 2.42 [95% CI, 1.63 to 3.60]), longer progression-free survival (hazard ratio [HR], 0.48 [95% CI, 0.36 to 0.63]), and longer overall survival (HR, 0.67 [95% CI, 0.46 to 0.97]). No associations were observed between therapy type and immune effector cell-associated neurotoxicity syndrome, any CRS, severe cytopenia at days 30 and 90, or nonrelapse mortality. We observed consistent findings when repeating the analyses restricting the ide-cel cohort to patients infused during the same time period as Food and Drug Administration approval for cilta-cel (≥March 2022).

CONCLUSION: Cilta-cel demonstrated superior efficacy and survival, with higher incidence of certain toxicities, compared with ide-cel.},
}

@article {pmid39964269,
year = {2025},
author = {Lawson, MB and Zhu, W and Miglioretti, DL and Onega, T and Henderson, LM and Rauscher, GH and Kerlikowske, K and Sprague, BL and Bowles, EJA and O'Meara, ES and Tosteson, ANA and diFlorio-Alexander, RM and Hubbard, RA and Lee, JM and Lee, CI},
title = {Disparities in Standard-of-Care, Advanced, and Same-Day Diagnostic Services among Patients with Abnormal Screening Mammography.},
journal = {Radiology},
volume = {314},
number = {2},
pages = {e241673},
doi = {10.1148/radiol.241673},
pmid = {39964269},
issn = {1527-1315},
mesh = {Humans ; Female ; *Mammography/statistics & numerical data/methods ; Middle Aged ; Aged ; Retrospective Studies ; *Breast Neoplasms/diagnostic imaging ; Adult ; *Healthcare Disparities/ethnology ; Aged, 80 and over ; *Early Detection of Cancer/methods ; United States ; Health Services Accessibility ; Biopsy/statistics & numerical data ; },
abstract = {Background Diagnostic imaging and biopsy are used to evaluate abnormal screening mammography. Differences in on-site availability and receipt of these diagnostic services may contribute to disparities in breast cancer outcomes across sociodemographic groups. Purpose To identify multilevel factors associated with on-site availability and receipt of diagnostic imaging and biopsy after screening mammography. Materials and Methods This retrospective study included female patients (age range, 40-89 years) who underwent screening mammography at 136 facilities in the United States from January 2010 to December 2020. The primary exposure variables were race and ethnicity and neighborhood-level educational attainment, household income, and rurality. The adjustment variables were age, breast density, breast biopsy history, personal and family history of breast cancer, time from prior mammographic examination to screening mammography, screening modality, facility academic affiliation, and screening examination year. The relative risk (RR) of factors for on-site availability at screening facilities and undergoing standard-of-care imaging (ie, mammography and/or US) and advanced diagnostic imaging (ie, digital breast tomosynthesis, MRI) and biopsy, and undergoing any same-day diagnostic service and biopsy were estimated using modified Poisson regression. Results In total, 1 123 177 female patients (median age, 59 years; IQR, 51-67 years) underwent 3 519 502 screening mammographic examinations: 10.3% Asian patients (362 440 of 3 519 502), 12.7% Black patients (447 777 of 3 519 502), 6.5% Hispanic patients (227 177 of 3 519 502), 68.3% White patients (2 403 159 of 3 519 502), and 2.2% all other races and ethnicities (78 949 of 3 519 502). In most fully adjusted models, race or ethnicity and neighborhood-level socioeconomic status were not associated with on-site diagnostic service availability. However, compared with White patients, patients belonging to racial and ethnic minority groups were less likely to undergo same-day diagnostic services after abnormal screening mammography (Asian patients: RR, 0.74 [95% CI: 0.64, 0.85]; Black patients: RR, 0.56 [95% CI: 0.49, 0.63]; Hispanic patients: RR, 0.61 [95% CI: 0.52, 0.71]). Black patients were less likely to undergo same-day biopsies after an abnormal diagnostic workup (RR, 0.46; 95% CI: 0.33, 0.65). Conclusion Although no evidence existed that on-site diagnostic service availability varied by race and ethnicity in most models, patients in racial and ethnic minority groups were less likely to be provided same-day diagnostic services and Black patients were less likely to undergo same-day biopsy. © RSNA, 2025 Supplemental material is available for this article. See also the editorial by Mullen in this issue.},
}

Humans
Female
*Mammography/statistics & numerical data/methods
Middle Aged
Aged
Retrospective Studies
*Breast Neoplasms/diagnostic imaging
Adult
*Healthcare Disparities/ethnology
Aged, 80 and over
*Early Detection of Cancer/methods
United States
Health Services Accessibility
Biopsy/statistics & numerical data

@article {pmid39963309,
year = {2025},
author = {Wadden, E and Lai, C and Grivas, P and Bhatia, S and Portuguese, AJ and Salem, JE and Moslehi, JJ and Cheng, RK},
title = {Successful treatment of immune checkpoint inhibitor-associated fulminant myocarditis with abatacept and ruxolitinib: a case report.},
journal = {European heart journal. Case reports},
volume = {9},
number = {2},
pages = {ytaf019},
pmid = {39963309},
issn = {2514-2119},
abstract = {BACKGROUND: Immune checkpoint inhibitors (ICIs) are a class of cancer immunotherapy with growing indications for treatment of various malignancies. Immune checkpoint inhibitors are monoclonal antibodies that block inhibitory pathways in immune cells, including cytotoxic T lymphocyte antigen-4 (CTLA4), programmed death 1 receptor (PD1), and programmed cell death ligand-1 (PDL1), to activate the immune system. However, these agents can disrupt self-tolerance and lead to immune-related adverse events. Fulminant myocarditis, a feared complication of ICIs, can be highly fatal, and there is a need for effective treatment options.

CASE SUMMARY: A 70-year-old patient with recurrent metastatic disease of urothelial carcinoma subsequently developed fulminant myocarditis after receiving eight cycles of pembrolizumab. He developed cardiogenic shock and required inotropes and a percutaneous microaxial flow pump placement for temporary mechanical circulatory support. He received methylprednisolone initially and then was started on second-line immunosuppression agents, ruxolitinib and abatacept, for steroid-refractory myocarditis. Abatacept is thought to inhibit activation of T-cell CTLA4 and PD1/PDL1 pathways and reverse ICI-activated pathways. Ruxolitinib is a Janus kinase inhibitor that impairs immune activation through suppressing cytokine sensing and production and T-cell activation. After these treatments, the patient subsequently clinically improved and his myocarditis resolved.

DISCUSSION: This case highlights ICI myocarditis refractory to corticosteroids leading to treatment with second-line immunosuppression. As immunotherapies are increasingly applied to a broader range of cancers, further research is needed to evaluate the optimal treatment strategy for ICI-related myocarditis and other immune-related adverse events.},
}

@article {pmid39962532,
year = {2025},
author = {Hunter, NB and Peterson, LM and Specht, JM and Mankoff, DA and Muzi, M and Chen, DL and Gwin, WR and Vinayak, S and Davidson, NE and Linden, HM},
title = {Fluoroestradiol (FES) and Fluorodeoxyglucose (FDG) PET imaging in patients with ER+, HER2-positive or HER2-negative metastatic breast cancer.},
journal = {Breast cancer research : BCR},
volume = {27},
number = {1},
pages = {23},
pmid = {39962532},
issn = {1465-542X},
support = {CA72064/NH/NIH HHS/United States ; CA42045/NH/NIH HHS/United States ; },
mesh = {Humans ; Female ; *Fluorodeoxyglucose F18 ; *Breast Neoplasms/pathology/metabolism/diagnostic imaging/drug therapy/mortality ; *Receptor, ErbB-2/metabolism ; *Receptors, Estrogen/metabolism ; Middle Aged ; *Positron-Emission Tomography/methods ; Retrospective Studies ; Aged ; Adult ; *Estradiol/analogs & derivatives ; Neoplasm Metastasis ; Radiopharmaceuticals ; Aged, 80 and over ; },
abstract = {BACKGROUND: [18]F-Fluorodeoxyglucose (FDG) and [18]F-Fluorestradiol (FES) have been FDA approved for measuring tumor glycolytic activity and estrogen receptor (ER) uptake, respectively, in clinical positron emission tomography (PET) imaging for patients with hormone-receptor (HR) positive metastatic breast cancer (MBC), but little is known about its utility in patients with breast tumors that overexpress human epidermal growth factor 2 (HER2). We hypothesize that comparing patterns of FDG and FES uptake in patients with HER2-positive versus HER2-negative MBC can guide further biologic and clinical studies into the HR/HER2-positive phenotype.

METHODS: We conducted a retrospective study examining uptake in matched lesions for FES and FDG-PET scans, assessing these parameters in 213 patients with ER-positive/HER2-positive (n = 33) versus ER-positive/HER2-negative MBC (n = 180). We employed log-rank and t-tests to assess the association of HER2 status with outcome variables and the hypotheses that patients expressing HER2-positive disease lived longer than patient with HER2-negative disease.

RESULTS: No difference in FES or FDG avidity was observed between patients with HER2-negative or HER2-positive tumor status. Limited data also suggests that patients with HER2-positive disease had better overall survival (p = 0.024), than those with HER2-negative disease, but not time-to-progression between the same patient cohorts.

CONCLUSION: This retrospective analysis suggests that there is a possible role for future trials using FES-PET in helping to select patients with ER+/HER2-positive primary tumors who retain ER expression at all sites of disease and may benefit from endocrine therapy.},
}

Humans
Female
*Fluorodeoxyglucose F18
*Breast Neoplasms/pathology/metabolism/diagnostic imaging/drug therapy/mortality
*Receptor, ErbB-2/metabolism
*Receptors, Estrogen/metabolism
Middle Aged
*Positron-Emission Tomography/methods
Retrospective Studies
Aged
Adult
*Estradiol/analogs & derivatives
Neoplasm Metastasis
Radiopharmaceuticals
Aged, 80 and over

@article {pmid39962220,
year = {2025},
author = {Gang, M and Othus, M and Sandmaier, BM and Davis, C and Basom, RS and Walter, RB},
title = {Modulators of relapse risk in adults allografted for acute myeloid leukemia in measurable residual disease-positive remission.},
journal = {Bone marrow transplantation},
volume = {},
number = {},
pages = {},
pmid = {39962220},
issn = {1476-5365},
support = {T32-HL007093//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; P01-CA078902//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; P01-CA018029//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; P30-CA015704//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; },
}

@article {pmid39961473,
year = {2025},
author = {Munshi, PN and Olin, RL and Wall, S and McCurdy, SR and Al-Juhaishi, T and Baker, J and Bhatt, VR and Chokr, N and Dahi, P and DeFilipp, Z and Espinoza-Gutarra, M and Farhan, S and Gowda, L and Hamilton, BK and Inamoto, Y and Jayani, R and Kharfan-Dabaja, MA and Lin, R and Meyers, G and Mishra, A and Murthy, HS and Nawas, M and Rosko, AE and Ruiz, M and Sorror, ML and Sung, AD and Carpenter, PA and Hamadani, M and Artz, AS},
title = {US Geriatric Assessment Practices for Older Adults Undergoing Hematopoietic Cell Transplantation or CAR T- cell therapy: An ASTCT Physician Survey from the Aging Special Interest Group and Committee on Practice Guidelines.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.02.014},
pmid = {39961473},
issn = {2666-6367},
abstract = {Geriatric assessment (GA) may identify vulnerabilities and promote risk-stratification in older adults predisposed to toxicities after autologous (auto), allogeneic (allo) hematopoietic cell transplantation (HCT) and chimeric antigen T-cell therapies (CAR T). With increased utilization cellular therapies for older adults the American Society for Transplantation and Cellular Therapy (ASTCT) Committee on Practice Guidelines and its Special Interest Group for Aging (SIG) conducted an online cross-sectional survey between April 2023 and August 2023 to determine transplantation and cellular therapy physicians' practice patterns regarding GA in older patients receiving HCT and CAR T-cell therapies. E-mail surveys were sent to 1168 ASTCT physician members and only 96 (8.2%) respondents completed the survey. Most (86%) were affiliated with university/teaching centers and 70% had a combined HCT and cellular therapy practice. More than 50% of respondents were interested in pursuing GA but 68% described barriers. The top two recognized barriers to GA were lack of time (96%) and clinical support staff (90%). Despite interest, only 15% respondents reported to know the domains of GA 'well'. Among those using GA, the minimum age used for routine GA was 65 years for allo-HCT and CAR T in over 91% respondents. Taken together, we recommend the HCT community leadership and GA experts combine efforts to address the gap in GA uptake and implementation.},
}

@article {pmid39960754,
year = {2025},
author = {Estevam, GO and Linossi, E and Rao, J and Macdonald, CB and Ravikumar, A and Chrispens, KM and Capra, JA and Coyote-Maestas, W and Pimentel, H and Collisson, EA and Jura, N and Fraser, JS},
title = {Mapping kinase domain resistance mechanisms for the MET receptor tyrosine kinase via deep mutational scanning.},
journal = {eLife},
volume = {13},
number = {},
pages = {},
pmid = {39960754},
issn = {2050-084X},
support = {GM145238/GM/NIGMS NIH HHS/United States ; R01 CA239604/CA/NCI NIH HHS/United States ; LM013434/NH/NIH HHS/United States ; S10 OD028511/OD/NIH HHS/United States ; R35 GM145238/GM/NIGMS NIH HHS/United States ; CA239604/CA/NCI NIH HHS/United States ; R01 LM013434/LM/NLM NIH HHS/United States ; },
mesh = {*Proto-Oncogene Proteins c-met/genetics/metabolism ; Humans ; *Protein Kinase Inhibitors/pharmacology ; *Mutation ; *Drug Resistance, Neoplasm/genetics ; Protein Domains ; DNA Mutational Analysis/methods ; },
abstract = {Mutations in the kinase and juxtamembrane domains of the MET Receptor Tyrosine Kinase are responsible for oncogenesis in various cancers and can drive resistance to MET-directed treatments. Determining the most effective inhibitor for each mutational profile is a major challenge for MET-driven cancer treatment in precision medicine. Here, we used a deep mutational scan (DMS) of ~5764 MET kinase domain variants to profile the growth of each mutation against a panel of 11 inhibitors that are reported to target the MET kinase domain. We validate previously identified resistance mutations, pinpoint common resistance sites across type I, type II, and type I ½ inhibitors, unveil unique resistance and sensitizing mutations for each inhibitor, and verify non-cross-resistant sensitivities for type I and type II inhibitor pairs. We augment a protein language model with biophysical and chemical features to improve the predictive performance for inhibitor-treated datasets. Together, our study demonstrates a pooled experimental pipeline for identifying resistance mutations, provides a reference dictionary for mutations that are sensitized to specific therapies, and offers insights for future drug development.},
}

*Proto-Oncogene Proteins c-met/genetics/metabolism
Humans
*Protein Kinase Inhibitors/pharmacology
*Mutation
*Drug Resistance, Neoplasm/genetics
Protein Domains
DNA Mutational Analysis/methods

@article {pmid39959858,
year = {2025},
author = {Ninga, X and Sun, Y and Pan, Y and Gilbert, PB},
title = {Regression analysis of semiparametric Cox-Aalen transformation models with partly interval-censored data.},
journal = {Electronic journal of statistics},
volume = {19},
number = {1},
pages = {240-290},
pmid = {39959858},
issn = {1935-7524},
support = {R37 AI054165/AI/NIAID NIH HHS/United States ; UM1 AI068635/AI/NIAID NIH HHS/United States ; },
abstract = {Partly interval-censored data, comprising exact and intervalcensored observations, are prevalent in biomedical, clinical, and epidemiological studies. This paper studies a flexible class of the semiparametric Cox-Aalen transformation models for regression analysis of such data. These models offer a versatile framework by accommodating both multiplicative and additive covariate effects and both constant and time-varying effects within a transformation, while also allowing for potentially time-dependent covariates. Moreover, this class of models includes many popular models such as the semiparametric transformation model, the Cox-Aalen model, the stratified Cox model, and the stratified proportional odds model as special cases. To facilitate efficient computation, we formulate a set of estimating equations and propose an Expectation-Solving (ES) algorithm that guarantees stability and rapid convergence. Under mild regularity assumptions, the resulting estimator is shown to be consistent and asymptotically normal. The validity of the weighted bootstrap is also established. A supremum test is proposed to test the time-varying covariate effects. Finally, the proposed method is evaluated through comprehensive simulations and applied to analyze data from a randomized HIV/AIDS trial.},
}

@article {pmid39956433,
year = {2025},
author = {Wilson, MH and Harrington, J and Suh, J and Fearon, C and Reavis, M and Srisatidnarakul, S and Swetky, M and Warren, N and Badalucco, A and Adams Barker, CM and Nandakumar, S and Pergam, SA},
title = {Isolation Precautions Associated with COVID-19 Infections Among Immunocompromised Populations: A Multi-Center Study of Nine National Cancer Institute-Designated Comprehensive Cancer Centers.},
journal = {American journal of infection control},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajic.2025.02.002},
pmid = {39956433},
issn = {1527-3296},
abstract = {BACKGROUND: Nine Comprehensive Cancer Centers sought to understand COVID-19 infection management experiences through the pandemic to improve future immunocompromised host guideline development.

METHODS: Volunteers from Comprehensive Cancer Center Infection Prevention and Control (C3IC) completed two surveys on COVID-19 practices from March 2020 to December 2023. Three reviewers independently validated qualitative analysis of findings. Virtual meetings were leveraged to review information gathered, discuss findings, and identify themes among respondents.

RESULTS: 100% (9/9) of respondents changed in COVID-19-associated isolation discontinuation guidance at least once. All (9/9) included patient immune status as criterion. All (9/9) required PCR clearance testing at some point in the pandemic, 6 of 9 (66%) continued to require clearance testing at the time of the survey; Only 1 of 9 (11%) allowed antigen testing to meet criteria. Cycle threshold (CT) values were inconsistently referenced and considered related to isolation management. Seven isolation titles were noted across 9 institutions, despite near agreement on measures employed.

DISCUSSION: Variability existed in COVID-19 management among study participants despite serving similar populations, which may stem from limited data supporting understanding of viral transmissibility in immunocompromised hosts.

CONCLUSIONS: Guideline development for immunocompromised hosts, potential drivers for viral evolution, can lack clarity for consistent management of the population. Engaging subject matters in these populations in future guideline development will improve infection prevention in healthcare settings.},
}

@article {pmid39955465,
year = {2025},
author = {Chow, EJ and Blythe, NA and Cushing-Haugen, KL and Duggan, C and Baker, KS and Cole, AM and Green, S and Guiterrez, AI and Lee, E and Linden, HM and Mendoza, JA and Ohlsen, TJD and Ortblad, KF and Schwartz, SM and Yung, RL and Ceballos, RM},
title = {Enhancing survivorship care among Hispanic/Latino cancer survivors via lay health educators: results of a pilot randomized trial.},
journal = {Journal of cancer survivorship : research and practice},
volume = {},
number = {},
pages = {},
pmid = {39955465},
issn = {1932-2267},
support = {CA015704/NH/NIH HHS/United States ; CA258105/NH/NIH HHS/United States ; CA258105/NH/NIH HHS/United States ; CA015704/NH/NIH HHS/United States ; CA015704/NH/NIH HHS/United States ; 75N91020C00005/NH/NIH HHS/United States ; CA258105/NH/NIH HHS/United States ; CA015704/NH/NIH HHS/United States ; HHSN261201800004I/NH/NIH HHS/United States ; CA258105/NH/NIH HHS/United States ; },
abstract = {PURPOSE: Assess the feasibility, acceptability, and preliminary efficacy of lay health educators to enhance Hispanic/Latino survivors' knowledge of their cancer history, screening needs, and health-related self-efficacy.

METHODS: Hispanic/Latino survivors diagnosed within 5 years were recruited from three clinics and a regional cancer registry. Survivors were randomized to receive a personalized survivorship care plan (SCP; control) or SCP plus telephone session with a bilingual-bicultural lay health educator (intervention). Survivors were reassessed after 3 months. Primary outcomes were feasibility (meeting accrual, n = 60-100) and acceptability of the SCP and education session. Secondary outcomes were changes in survivors' knowledge of their cancer history, screening needs, and health-related self-efficacy.

RESULTS: Ninety-fine survivors (median age 55 years, 78% female, 56% low/marginal health literacy) were randomized (n = 48 intervention). Seventy-nine completed the study; most found the SCP useful (82% intervention; 68% control); 84% of the intervention group rated the education session useful. Over time, both groups had improved knowledge of their cancer history (accuracy increased from 71.5 ± 16.4% to 73.8 ± 15.0%; p = 0.19) although differences over time and between groups were not statistically significant. At follow-up compared with baseline, participants were more likely to report plans for future screening: cervical (57% versus 31%, p = 0.002); colorectal (39% versus 26%, p = 0.10). Although the change in self-efficacy did not differ between study groups, self-efficacy significantly improved within the control group over time (0.3; 95% CI 0.1, 0.5).

CONCLUSIONS: Hispanic/Latino survivors found the SCP and education session acceptable. SCPs alone may improve knowledge and adherence to cancer screening.

Provision of a SCP may benefit Hispanic/Latino survivors.

CLINICAL TRIAL REGISTRATION: clinicaltrials.gov NCT04081779.},
}

@article {pmid39954698,
year = {2025},
author = {Ortblad, KF and Ngure, K},
title = {Safety of dapivirine vaginal rings during breastfeeding.},
journal = {The lancet. HIV},
volume = {},
number = {},
pages = {},
doi = {10.1016/S2352-3018(24)00342-4},
pmid = {39954698},
issn = {2352-3018},
}

@article {pmid39954697,
year = {2025},
author = {Noguchi, LM and Owor, M and Mgodi, NM and Gati Mirembe, B and Dadabhai, S and Horne, E and Gundacker, H and Richardson, BA and Bunge, K and Scheckter, R and Song, M and Marzinke, MA and Anderson, PL and Livant, E and Jacobson, C and Piper, JM and Chakhtoura, N and Hillier, SL and Balkus, JE and , },
title = {Safety and drug quantification of the dapivirine vaginal ring and oral pre-exposure prophylaxis in breastfeeding mother-infant pairs (MTN-043): a phase 3B, open-label, randomised trial.},
journal = {The lancet. HIV},
volume = {},
number = {},
pages = {},
doi = {10.1016/S2352-3018(24)00306-0},
pmid = {39954697},
issn = {2352-3018},
abstract = {BACKGROUND: In 2021, WHO recommended dapivirine vaginal rings (DVRs) for HIV prevention, but noted evidence gaps for breastfeeding populations. This trial aimed to describe safety profiles associated with DVRs and oral pre-exposure prophylaxis (PrEP) use during breastfeeding and to summarise study-drug quantification and concentrations for mothers and infants.

METHODS: Microbicide Trials Network (MTN)-043 was a phase 3b, open-label, randomised trial in which mother-infant pairs were recruited from local health facilities and enrolled at four HIV clinical trial sites in Malawi, South Africa, Uganda, and Zimbabwe. Eligible mothers (aged ≥18 years) were HIV-negative, exclusively breastfeeding one infant (aged 6-12 weeks, birthweight ≥2000 g), and had not been exposed to HIV post-exposure prophylaxis in the previous 6 months. Mother-infant pairs were randomly assigned (3:1) via a computer-generated sequence to 12 weeks of 25 mg monthly DVR or daily oral PrEP (200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate), with stratification by site using a permuted block design. Participants and staff were aware of study product assignment. Primary outcomes were maternal and infant safety (all serious adverse events and grade 3 or worse adverse events) and drug concentrations, which were measured in maternal plasma, maternal blood, breastmilk, infant plasma, and infant blood. All mother-infant pairs who received at least one dose of study product were included in the primary safety analysis, and those with at least one post-enrolment drug concentration result were included in the drug quantification analysis. The trial was registered at ClinicalTrials.gov (NCT04140266).

FINDINGS: Between Sept 24, 2020, and July 29, 2021, 197 mother-infant pairs enrolled (148 on DVR and 49 on PrEP), all of whom received at least one dose of study product and were included in the primary safety analysis. Two (1%) of 148 mothers in the DVR group had serious adverse events, and three (2%) in the DVR group and two (4%) in the oral PrEP group had a grade 3 or worse adverse event; four (3%) of 148 infants in the DVR group had a serious adverse event, and ten (7%) in the DVR group and one (2%) in the oral PrEP group had a grade 3 or worse adverse event. No mother or infant in the oral PrEP group had a serious adverse event. No HIV infections were detected. 144 participants in the DVR group and 48 in the oral PrEP group had at least one post-enrolment drug concentration result. Quantifiable median dapivirine concentrations ranged from 656·0 (IQR 407·0-878·0) pg/mL at week 1 to 558·5 (282·0-778·0) pg/mL at month 3, but were observed infrequently (5-15%) in specimens from infants, with median concentrations below the limit of quantification at all visits. Median tenofovir diphosphate concentrations ranged from 263·0 (193·0-363·0) fmol/punch at week 1 to 777·0 (381·0-1241·0) fmol/punch at month 3, but were not observed in specimens from infants, with all concentrations below the limit of quantification at all visits.

INTERPRETATION: Increased risk of HIV acquisition in the postnatal period, favourable product safety profile, and low drug exposures among infants support the recommendation for DVRs as an additional HIV prevention choice during breastfeeding.

FUNDING: US National Institutes of Health.},
}

@article {pmid39953849,
year = {2025},
author = {Dontchos, BN and Phelps, MD and Rahbar, H and Lam, DL},
title = {Pre-Treatment Breast MRI: Clinical Indications, Outcomes, and Future Directions.},
journal = {Journal of magnetic resonance imaging : JMRI},
volume = {},
number = {},
pages = {},
doi = {10.1002/jmri.29741},
pmid = {39953849},
issn = {1522-2586},
abstract = {Breast MRI is the most sensitive modality for assessing the extent of disease in patients with newly-diagnosed breast cancer because it identifies clinically- and mammographically-occult breast cancers. Though highly sensitive, breast MRI has lower specificity that may result in false positive findings and potential overestimation of disease if additional MRI findings are not biopsied prior to surgery. It had been anticipated that the superior cancer detection rate of pre-treatment MRI would translate to improved immediate (surgical re-excision) and long-term patient outcomes such as breast cancer recurrence and survival rates, but studies have not necessarily supported this assumption. In this review, current recommendations and utilization of breast MRI for pre-treatment local staging of breast cancer will be presented, with an emphasis on specific clinical scenarios for patient selection and its impact on short- and long-term patient clinical outcomes. We will also present new evidence that pre-treatment MRI may support de-escalation of treatment and discuss emerging advanced MRI techniques that may improve diagnostic performance.},
}

@article {pmid39953405,
year = {2025},
author = {Soussand, F and Abdou, AY and Sanchez, M and Huynh, BT and Giese, C and Tran-Kiem, C and Béraud, G and Guillemot, D and Cauchemez, S and Opatowski, L and Bosetti, P},
title = {Evolution of social contacts patterns in France over the SARS-CoV-2 pandemic: results from the SocialCov survey.},
journal = {BMC infectious diseases},
volume = {25},
number = {1},
pages = {224},
pmid = {39953405},
issn = {1471-2334},
mesh = {Humans ; *COVID-19/epidemiology/transmission/prevention & control ; France/epidemiology ; Adult ; Middle Aged ; Male ; Female ; Surveys and Questionnaires ; Aged ; Adolescent ; *SARS-CoV-2 ; Young Adult ; *Contact Tracing ; Child ; Pandemics ; Child, Preschool ; Infant ; Aged, 80 and over ; Quarantine ; },
abstract = {BACKGROUND: Non-pharmaceutical measures such as lockdowns, curfews and place closures were implemented in France during 2020-2022 to reduce contacts in the population, to limit the spread of SARS-CoV-2 and reduce COVID-19 healthcare burden. Individuals also changed their behaviours as a response to the pandemic. Here, we present the results of the SocialCov survey that characterise the evolution of contacts in France between December 2020 and May 2022 to better understand the short and long term impact of these interventions on social mixing.

METHODS: A questionnaire was advertised over six independent communication campaigns through the governmental application TousAntiCovid between December 2020 and June 2022. Participants were asked to detail social contacts in the previous day, including contact age, location, duration and type (physical/conversational).

RESULTS: Over the six distinct campaigns, 44,396 individuals participated in the survey, declaring 300,735 contacts in total. The patterns of contacts strongly evolved over time, along with the progressive easing of national mitigation measures. The number of contacts in the French population increased from 5.3 contacts per day on average in December 2020 to 9.7 in May 2022. Mixing patterns were affected by age of participants, holidays and weekends. Healthcare workers declared 18.4 contacts on average during working days, roughly twice more than other workers. Reported risk perception changed throughout the two year period.

CONCLUSIONS: Results provide a detailed picture of contact evolution over the years 2020-2022 in France. In addition to a major evolution of contact density over time, this study highlights strong heterogeneities in contact patterns according to age, employment and weekend/vacation periods. The contact matrices provided here can be used to inform age-stratified transmission models of respiratory pathogens in the context of implementation of multiple non-pharmaceutical measures.},
}

Humans
*COVID-19/epidemiology/transmission/prevention & control
France/epidemiology
Adult
Middle Aged
Male
Female
Surveys and Questionnaires
Aged
Adolescent
*SARS-CoV-2
Young Adult
*Contact Tracing
Child
Pandemics
Child, Preschool
Infant
Aged, 80 and over
Quarantine

@article {pmid39951468,
year = {2025},
author = {Chen, KY and Toro-Moreno, M and Subramaniam, AR},
title = {GitHub enables collaborative and reproducible laboratory research.},
journal = {PLoS biology},
volume = {23},
number = {2},
pages = {e3003029},
pmid = {39951468},
issn = {1545-7885},
mesh = {*Software ; Laboratories ; Reproducibility of Results ; Humans ; Cooperative Behavior ; Workflow ; },
abstract = {GitHub, a platform widely used in software development, offers a robust framework for documenting all activities of laboratory research projects. This Community Page highlights the benefits of, and provides guidance for, incorporating the GitHub ecosystem into "wet" lab workflows.},
}

*Software
Laboratories
Reproducibility of Results
Humans
Cooperative Behavior
Workflow

@article {pmid39951264,
year = {2025},
author = {Chung, DH and Caverly, TJ and Schipper, MJ and Hofer, TP and Gulati, R and Rose, BS and Caram, MEV and Tsao, PA and Stensland, KD and Elliott, D and Saini, SD and Bryant, AK},
title = {Prostate Cancer Mortality in Men Aged 70 Years Who Recently Underwent Prostate-Specific Antigen Screening.},
journal = {JAMA network open},
volume = {8},
number = {2},
pages = {e2459766},
pmid = {39951264},
issn = {2574-3805},
mesh = {Humans ; Male ; *Prostatic Neoplasms/mortality/diagnosis/blood ; *Prostate-Specific Antigen/blood ; Aged ; *Early Detection of Cancer/methods/statistics & numerical data ; Cohort Studies ; United States/epidemiology ; Risk Assessment/methods ; Mass Screening/methods/statistics & numerical data ; },
abstract = {IMPORTANCE: Continuing prostate-specific antigen (PSA) screening after age 70 years might benefit men at high risk of prostate cancer-specific mortality (PCSM) or metastatic prostate cancer (mPCa), but the relative value of clinical factors (race and ethnicity, competing mortality, and PSA history) in identifying men at higher vs lower risk is unknown.

OBJECTIVE: To examine the value of PSA levels, race and ethnicity, and competing mortality in risk stratification for PCSM and mPCa in men after age 70 years.

In this cohort study, clinical data of all men receiving health care through the Veterans Health Administration who turned age 70 years between 2008 and 2020 and had a normal screening PSA value between age 65 and 69 years (<4 ng/mL [baseline PSA]) and no prior history of prostate cancer or biopsy were examined. The data cutoff date was December 26, 2023.

EXPOSURE: The most recent screening PSA value from age 65 to 69 years, self-reported race and ethnicity, and competing mortality risk derived from a machine learning model.

MAIN OUTCOME AND MEASURES: The 10-year absolute risk of PCSM and mPCa were determined using regression modeling.

RESULTS: The cohort included 921 609 men who turned 70 years between 2008 and 2020; 11% of whom self-reported as Black and 82% as White race. Between age 65 and 70 years, 45% of patients had a baseline PSA of less than 1.00 ng/mL, and 32% had a baseline PSA of 1.00 to 1.99 ng/mL. Most patients (87%) continued to undergo screening past age 70 years, with little variation by competing mortality risk or race and ethnicity. The 10-year cumulative incidence of PCSM was 0.26% overall, and 95% of men had a 10-year risk less than 0.73%. Higher baseline PSA level between age 65 and 69 years was associated with 10-year PCSM risk (0.79% for 3.00-3.99 ng/mL vs 0.10% for 0.20-0.99 ng/mL), race and ethnicity (0.36% for Black vs 0.25% for White), and competing mortality (0.24% for the highest quintile vs 0.21% for the lowest quintile). Similar results were found for mPCa. Low PSA (0.20-0.99 ng/mL) was associated with very low PCSM and mPCa risk, even among Black men in the healthiest quintile of competing mortality risk (10-year PCSM risk, 0.08% [95% CI, 0.01%-0.44%]; 10-year mPCa risk 0.24% [95% CI, 0.10%-0.52%]).

CONCLUSIONS AND RELEVANCE: In this cohort study, the findings suggest that most men receiving care through the VHA continue PSA screening after age 70 years despite low absolute 10-year PCSM risks. The PSA values from age 65 to 69 years may be highly informative for adverse prostate cancer outcomes after age 70 years, with a PSA less than 1 ng/mL associated with a very low risk of long-term PCSM and mPCa.},
}

Humans
Male
*Prostatic Neoplasms/mortality/diagnosis/blood
*Prostate-Specific Antigen/blood
Aged
*Early Detection of Cancer/methods/statistics & numerical data
Cohort Studies
United States/epidemiology
Risk Assessment/methods
Mass Screening/methods/statistics & numerical data

@article {pmid39951243,
year = {2025},
author = {Javid, SH and Kazerouni, AS and Hippe, DS and Hirano, M and Schnuck-Olapo, J and Biswas, D and Bryant, ML and Li, I and Xiao, J and Kim, AG and Guo, A and Dontchos, B and Kilgore, M and Kim, J and Partridge, SC and Rahbar, H},
title = {ASO Visual Abstract: Preoperative MRI to Predict Upstaging of DCIS to Invasive Cancer at Surgery.},
journal = {Annals of surgical oncology},
volume = {},
number = {},
pages = {},
doi = {10.1245/s10434-025-16994-7},
pmid = {39951243},
issn = {1534-4681},
}

@article {pmid39950338,
year = {2025},
author = {Iyer, KR and Clarke, SL and Guarischi-Sousa, R and Gjoni, K and Heath, AS and Young, EP and Stitziel, NO and Laurie, C and Broome, JG and Khan, AT and Lewis, JP and Xu, H and Montasser, ME and Ashley, KE and Hasbani, NR and Boerwinkle, E and Morrison, AC and Chami, N and Do, R and Rocheleau, G and Lloyd-Jones, DM and Lemaitre, RN and Bis, JC and Floyd, JS and Kinney, GL and Bowden, DW and Palmer, ND and Benjamin, EJ and Nayor, M and Yanek, LR and Kral, BG and Becker, LC and Kardia, SLR and Smith, JA and Bielak, LF and Norwood, AF and Min, YI and Carson, AP and Post, WS and Rich, SS and Herrington, D and Guo, X and Taylor, KD and Manson, JE and Franceschini, N and Pollard, KS and Mitchell, BD and Loos, RJF and Fornage, M and Hou, L and Psaty, BM and Young, KA and Regan, EA and Freedman, BI and Vasan, RS and Levy, D and Mathias, RA and Peyser, PA and Raffield, LM and Kooperberg, C and Reiner, AP and Rotter, JI and Jun, G and de Vries, PS and Assimes, TL},
title = {Unveiling the Genetic Landscape of Coronary Artery Disease Through Common and Rare Structural Variants.},
journal = {Journal of the American Heart Association},
volume = {},
number = {},
pages = {e036499},
doi = {10.1161/JAHA.124.036499},
pmid = {39950338},
issn = {2047-9980},
support = {K26 DK138425/DK/NIDDK NIH HHS/United States ; R01 DK117445/DK/NIDDK NIH HHS/United States ; R01 HL163972/HL/NHLBI NIH HHS/United States ; R01 HL175681/HL/NHLBI NIH HHS/United States ; },
abstract = {BACKGROUND: Genome-wide association studies have identified several hundred susceptibility single nucleotide variants for coronary artery disease (CAD). Despite single nucleotide variant-based genome-wide association studies improving our understanding of the genetics of CAD, the contribution of structural variants (SVs) to the risk of CAD remains largely unclear.

METHOD AND RESULTS: We leveraged SVs detected from high-coverage whole genome sequencing data in a diverse group of participants from the National Heart Lung and Blood Institute's Trans-Omics for Precision Medicine program. Single variant tests were performed on 58 706 SVs in a study sample of 11 556 CAD cases and 42 907 controls. Additionally, aggregate tests using sliding windows were performed to examine rare SVs. One genome-wide significant association was identified for a common biallelic intergenic duplication on chromosome 6q21 (P=1.54E-09, odds ratio=1.34). The sliding window-based aggregate tests found 1 region on chromosome 17q25.3, overlapping USP36, to be significantly associated with coronary artery disease (P=1.03E-10). USP36 is highly expressed in arterial and adipose tissues while broadly affecting several cardiometabolic traits.

CONCLUSIONS: Our results suggest that SVs, both common and rare, may influence the risk of coronary artery disease.},
}

@article {pmid39660994,
year = {2025},
author = {Livingston, JA and Blay, JY and Trent, J and Valverde, C and Agulnik, M and Gounder, M and Le Cesne, A and McKean, M and Wagner, MJ and Stacchiotti, S and Agresta, S and Quintás-Cardama, A and Reilly, SA and Healy, K and Hickman, D and Zhao, T and Ballesteros-Perez, A and Khalil, A and Collins, MP and Piel, J and Horrigan, K and Lefkovith, A and Innis, S and Lazar, AJ and Cote, GM and Wagner, AJ},
title = {A Phase I Study of FHD-609, a Heterobifunctional Degrader of Bromodomain-Containing Protein 9, in Patients with Advanced Synovial Sarcoma or SMARCB1-Deficient Tumors.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {31},
number = {4},
pages = {628-638},
doi = {10.1158/1078-0432.CCR-24-2583},
pmid = {39660994},
issn = {1557-3265},
support = {//Foghorn Therapeutics Inc. (Foghorn)/ ; },
mesh = {Humans ; Male ; Female ; *Sarcoma, Synovial/drug therapy/genetics/pathology ; Middle Aged ; Adult ; Aged ; *Transcription Factors/genetics ; *Maximum Tolerated Dose ; *SMARCB1 Protein/genetics/deficiency ; Young Adult ; Treatment Outcome ; Antineoplastic Agents/adverse effects/administration & dosage/pharmacokinetics ; Bromodomain Containing Proteins ; },
abstract = {PURPOSE: FHD-609, a potent, selective, heterobifunctional degrader of bromodomain-containing protein 9 (BRD9), was evaluated for treating patients with advanced synovial sarcoma or SMARCB1-deficient tumors.

PATIENTS AND METHODS: In this multinational, open-label, phase I study (NCT04965753), patients received FHD-609 intravenously at escalating doses either twice weekly (5-80 mg; n = 40) or once weekly (40-120 mg; n = 15).

RESULTS: Fifty-five patients received FHD-609 for a median of 43 days. The maximum tolerated doses were 40 mg twice weekly and the equivalent weekly dose, 80 mg once weekly. Dose-limiting toxicities of QTc (heart rate-corrected QT interval) prolongation and syncope were observed at 40 and 60 mg twice weekly. Treatment-related adverse events were predominantly grades 1 to 2 in severity, most commonly dysgeusia (40%), dry mouth (29.1%), fatigue (27.3%), and anemia (25.5%). Eleven (20%) patients had treatment-emergent QTc (Fridericia formula) prolongation preceded by T-wave inversions; 21 (38.2%) patients had T-wave inversions without further cardiac events or ECG abnormalities. FHD-609 showed dose-dependent increases in pharmacokinetic exposure, with no substantial accumulation. Extensive BRD9 degradation in tumor tissue corresponded to the downregulation of cancer cell proliferation gene sets. One (2%) patient achieved a partial response; eight (15%) patients achieved stable disease, which lasted longer than 6 months in two patients.

CONCLUSIONS: FHD-609 showed dose-dependent increases in systemic FHD-609 exposure and pharmacodynamic response profiles. The maximum tolerated doses were identified (40 mg twice weekly/80 mg once weekly) and preliminary clinical activity was observed. Future studies of BRD9 degraders will require strict cardiac monitoring given the QTc prolongation observed in this study.},
}

Humans
Male
Female
*Sarcoma, Synovial/drug therapy/genetics/pathology
Middle Aged
Adult
Aged
*Transcription Factors/genetics
*Maximum Tolerated Dose
*SMARCB1 Protein/genetics/deficiency
Young Adult
Treatment Outcome
Antineoplastic Agents/adverse effects/administration & dosage/pharmacokinetics
Bromodomain Containing Proteins

@article {pmid39947884,
year = {2025},
author = {Chen, X and Patkar, N and Tembhare, P and Papagudi, S and Yeung, C and Kanagal Shamanna, R and Gujral, S and Wood, B and Naresh, KN},
title = {Fifth edition WHO classification: myeloid neoplasms.},
journal = {Journal of clinical pathology},
volume = {},
number = {},
pages = {},
doi = {10.1136/jcp-2024-210022},
pmid = {39947884},
issn = {1472-4146},
abstract = {The fifth edition of the WHO classification of haematolymphoid tumours (WHO-HEM5) introduces significant advancements in the understanding and diagnosis of myeloid neoplasms, emphasising molecular and genetic insights. This review highlights key updates from the revised fourth edition (WHO-HEM4R), particularly the integration of genetic criteria for disease classification. Many entities are now defined by specific genetic abnormalities, enhancing diagnostic precision and prognostic assessment. Notably, the elimination of the 20% blast threshold for acute myeloid leukaemia (AML) with specific defining genetic alterations reflects a shift towards genomic-driven diagnostics. Additional updates include the refined subclassification of myelodysplastic neoplasms (MDS) and MDS/myeloproliferative neoplasms, as well as the recognition of novel entities such as clonal haematopoiesis and MDS with biallelic TP53 inactivation, further expanding the spectrum of myeloid neoplasms. WHO-HEM5 illustrates the diagnostic utility of morphology, flow cytometry, immunohistochemistry and next-generation sequencing in resource-rich settings. However, its implementation in low-income and middle-income countries (LMICs) remains challenging due to limited access to advanced diagnostic tools. This review explores strategies to optimise diagnosis in resource-constrained environments, where morphology and immunophenotyping remain fundamental. By integrating molecular diagnostics with traditional methods, WHO-HEM5 aims to refine classification and facilitate risk stratification in the era of personalised medicine, providing haematopathologists and clinicians with an essential framework to navigate the complexities of myeloid neoplasms. The emphasis on advancing haematopathology practices worldwide, including in LMICs, demonstrates the ongoing commitment to improving global outcomes in haematological malignancies.},
}

@article {pmid39946483,
year = {2025},
author = {Henikoff, S and Zheng, Y and Paranal, RM and Xu, Y and Greene, JE and Henikoff, JG and Russell, ZR and Szulzewsky, F and Thirimanne, HN and Kugel, S and Holland, EC and Ahmad, K},
title = {RNA polymerase II at histone genes predicts outcome in human cancer.},
journal = {Science (New York, N.Y.)},
volume = {387},
number = {6735},
pages = {737-743},
doi = {10.1126/science.ads2169},
pmid = {39946483},
issn = {1095-9203},
mesh = {*RNA Polymerase II/metabolism ; Humans ; Animals ; Mice ; *Histones/metabolism ; Glioma/genetics ; Receptor, ErbB-2/genetics/metabolism ; Meningioma/genetics ; Breast Neoplasms/genetics ; Female ; S Phase ; Prognosis ; Chromatin/metabolism ; Aneuploidy ; Neoplasms/genetics ; Gene Expression Regulation, Neoplastic ; },
abstract = {Genome-wide hypertranscription is common in human cancer and predicts poor prognosis. To understand how hypertranscription might drive cancer, we applied our formalin-fixed paraffin-embedded (FFPE)-cleavage under targeted accessible chromatin method for mapping RNA polymerase II (RNAPII) genome-wide in FFPE sections. We demonstrate global RNAPII elevations in mouse gliomas and assorted human tumors in small clinical samples and discover regional elevations corresponding to de novo HER2 amplifications punctuated by likely selective sweeps. RNAPII occupancy at S-phase-dependent histone genes correlated with WHO grade in meningiomas, accurately predicted rapid recurrence, and corresponded to whole-arm chromosome losses. Elevated RNAPII at histone genes in meningiomas and diverse breast cancers is consistent with histone production being rate-limiting for S-phase progression and histone gene hypertranscription driving overproliferation and aneuploidy in cancer, with general implications for precision oncology.},
}

*RNA Polymerase II/metabolism
Humans
Animals
Mice
*Histones/metabolism
Glioma/genetics
Receptor, ErbB-2/genetics/metabolism
Meningioma/genetics
Breast Neoplasms/genetics
Female
S Phase
Prognosis
Chromatin/metabolism
Aneuploidy
Neoplasms/genetics
Gene Expression Regulation, Neoplastic

@article {pmid39943310,
year = {2025},
author = {Jyoti, D and Reeves, D and Gordon-Wylie, S and Eskey, C and Weaver, J},
title = {Improving Stroke Treatment Using Magnetic Nanoparticle Sensors to Monitor Brain Thrombus Extraction.},
journal = {Sensors (Basel, Switzerland)},
volume = {25},
number = {3},
pages = {},
pmid = {39943310},
issn = {1424-8220},
support = {1R43NS129419//1R43NS129419 and AI155224/ ; },
mesh = {Humans ; *Magnetite Nanoparticles/chemistry/therapeutic use ; *Thrombosis ; *Thrombectomy/methods/instrumentation ; *Stroke/therapy ; },
abstract = {(1) Background: Mechanical thrombectomy (MT) successfully treats ischemic strokes by extracting the thrombus, or clot, using a stent retriever to pull it through the blood vessel. However, clot slippage and/or fragmentation can occur. Real-time feedback to a clinician about attachment between the stent and clot could enable more complete removal. We propose a system whereby antibody-targeted magnetic nanoparticles (NPs) are injected via a microcatheter to coat the clot, oscillating magnetic fields excite the particles, and a small coil attached to the catheter picks up a signal that determines the proximity of the clot to the stent. (2) Methods: We used existing simulation code to model the signal from NPs distributed on a hemispherical clot with three orthogonally applied magnetic fields. An in vitro apparatus was built that applied fields and read out signals from a 1.5 mm pickup coil at a variable distance and orientation angle from a sample of 100 nm iron oxide core/shell NPs. (3) Results: Our simulations suggest that the sum of the voltages induced in the pickup coil from three orthogonal applied fields could localize a clot to within 180 µm, regardless of the exact orientation of the pickup coil, with further precision added via rotation-correction formulae. Our experimental system validated simulations; we estimated an in vitro distance recovery precision of 41 µm with a pickup coil 1 mm from the clot. (4) Conclusions: Magnetic NP sensing could be a safe and real-time method to estimate whether a clot is attached to the stent retriever during MT.},
}

Humans
*Magnetite Nanoparticles/chemistry/therapeutic use
*Thrombosis
*Thrombectomy/methods/instrumentation
*Stroke/therapy

@article {pmid39939790,
year = {2025},
author = {Adli, M and Przybyla, L and Burdett, T and Burridge, PW and Cacheiro, P and Chang, HY and Engreitz, JM and Gilbert, LA and Greenleaf, WJ and Hsu, L and Huangfu, D and Hung, LH and Kundaje, A and Li, S and Parkinson, H and Qiu, X and Robson, P and Schürer, SC and Shojaie, A and Skarnes, WC and Smedley, D and Studer, L and Sun, W and Vidović, D and Vierbuchen, T and White, BS and Yeung, KY and Yue, F and Zhou, T and , },
title = {MorPhiC Consortium: towards functional characterization of all human genes.},
journal = {Nature},
volume = {638},
number = {8050},
pages = {351-359},
pmid = {39939790},
issn = {1476-4687},
support = {U24 HG012674/HG/NHGRI NIH HHS/United States ; },
mesh = {Humans ; *Phenotype ; *Alleles ; *Genome, Human/genetics ; Genomics ; },
abstract = {Recent advances in functional genomics and human cellular models have substantially enhanced our understanding of the structure and regulation of the human genome. However, our grasp of the molecular functions of human genes remains incomplete and biased towards specific gene classes. The Molecular Phenotypes of Null Alleles in Cells (MorPhiC) Consortium aims to address this gap by creating a comprehensive catalogue of the molecular and cellular phenotypes associated with null alleles of all human genes using in vitro multicellular systems. In this Perspective, we present the strategic vision of the MorPhiC Consortium and discuss various strategies for generating null alleles, as well as the challenges involved. We describe the cellular models and scalable phenotypic readouts that will be used in the consortium's initial phase, focusing on 1,000 protein-coding genes. The resulting molecular and cellular data will be compiled into a catalogue of null-allele phenotypes. The methodologies developed in this phase will establish best practices for extending these approaches to all human protein-coding genes. The resources generated-including engineered cell lines, plasmids, phenotypic data, genomic information and computational tools-will be made available to the broader research community to facilitate deeper insights into human gene functions.},
}

Humans
*Phenotype
*Alleles
*Genome, Human/genetics
Genomics

@article {pmid39939524,
year = {2025},
author = {Adil, M and Kolarova, TR and Doebley, AL and Chen, LA and Tobey, CL and Galipeau, P and Rosen, S and Yang, M and Colbert, B and Patton, RD and Persse, TW and Kawelo, E and Reichel, JB and Pritchard, CC and Akilesh, S and Lockwood, CM and Ha, G and Shree, R},
title = {Preeclampsia risk prediction from prenatal cell-free DNA screening.},
journal = {Nature medicine},
volume = {},
number = {},
pages = {},
pmid = {39939524},
issn = {1546-170X},
support = {HL150169//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; HD086620//U.S. Department of Health & Human Services | NIH | NICHD | National Center for Medical Rehabilitation Research (NCMRR)/ ; T32GM007454//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; CA237746//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; CA280624//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; },
abstract = {Preeclampsia is characterized by placental dysfunction and results in significant morbidity, but reliable early prediction remains challenging. We investigated whether clinically obtained prenatal cell-free DNA (cfDNA) screening (PDNAS) using whole-genome sequencing (WGS) data can be leveraged to predict preeclampsia risk early in pregnancy (≤16 weeks). Using 1,854 routinely collected clinical PDNAS samples (median, 12.1 weeks) with low-coverage (0.5×) WGS data, we developed a framework to quantify maternal and fetal tissue signatures using nucleosome accessibility, revealing early placental and endothelial dysfunction. These signatures informed a prediction model for preeclampsia risk, which achieved a validation performance of 0.85 area under the receiver operating characteristic curve (AUC) (81% sensitivity at 80% specificity) for preterm phenotypes several months prior to disease onset in a separate cohort of 831 consecutively collected samples, and subsequently confirmed in an external cohort of 141 samples (AUC 0.84, 79% sensitivity). We demonstrate that assessment of cfDNA nucleosome accessibility from early-pregnancy cfDNA sequence data enables the detection of early placental and endothelial-tissue aberrations and may aid in the determination of preeclampsia risk.},
}

@article {pmid39939078,
year = {2025},
author = {Hsieh, RW and Symonds, LK and Siu, J and Cohen, SA},
title = {Identification of circulating tumor DNA as a biomarker for diagnosis and response to therapies in cancer patients.},
journal = {International review of cell and molecular biology},
volume = {391},
number = {},
pages = {43-93},
doi = {10.1016/bs.ircmb.2024.08.006},
pmid = {39939078},
issn = {1937-6448},
mesh = {Humans ; *Circulating Tumor DNA/blood ; *Biomarkers, Tumor/blood ; *Neoplasms/diagnosis/blood/therapy/genetics ; Treatment Outcome ; },
abstract = {The sampling of circulating biomarkers provides an opportunity for non-invasive evaluation and monitoring of cancer activity. In modern day practice, this has typically been in the form of circulating tumor DNA (ctDNA) detected in plasma. The field of ctDNA has been a burgeoning technology, with prominent applications for blood-based cancer screening and in disease status assessment, especially after curative-intent surgery to evaluate for minimal residual disease (MRD). Clinical applications for the latter show an incredibly high sensitivity in certain cancer types with a need for additional studies to determine how much clinical decision-making should be adapted based on ctDNA results and which cancer types, stages, and treatments are best informed by ctDNA results. This chapter provides an overview of ctDNA detection as tool for cancer screening, detecting MRD, and/or molecularly characterizing a cancer, highlighting the rapidly amassing research as a prognostic biomarker and emerging data on ctDNA as a predictive biomarker.},
}

Humans
*Circulating Tumor DNA/blood
*Biomarkers, Tumor/blood
*Neoplasms/diagnosis/blood/therapy/genetics
Treatment Outcome

@article {pmid39938471,
year = {2025},
author = {Colevas, AD and Cmelak, AJ and Pfister, DG and Spencer, S and Adkins, D and Birkeland, AC and Brizel, DM and Busse, PM and Caudell, JJ and Durm, G and Fakhry, C and Galloway, T and Geiger, JL and Gillison, ML and Glastonbury, C and Haddad, RI and Hicks, WL and Hitchcock, YJ and Jimeno, A and Juloori, A and Kase, M and Leizman, D and Maghami, E and Mell, LK and Mittal, BB and Pinto, HA and Price, K and Rocco, JW and Rodriguez, CP and Schwartz, D and Shah, JP and Sher, D and John, MS and Wang, H and Weinstein, G and Worden, F and Bruce, JY and Yom, SS and Zhen, W and Montgomery, S and Darlow, SD},
title = {NCCN Guidelines® Insights: Head and Neck Cancers, Version 2.2025.},
journal = {Journal of the National Comprehensive Cancer Network : JNCCN},
volume = {23},
number = {2},
pages = {2-11},
doi = {10.6004/jnccn.2025.0007},
pmid = {39938471},
issn = {1540-1413},
mesh = {Humans ; *Head and Neck Neoplasms/therapy/diagnosis/pathology ; Practice Guidelines as Topic ; Education, Medical, Continuing ; },
abstract = {The NCCN Guidelines for Head and Neck Cancers address tumors arising in the oral cavity (including mucosal lip), pharynx, larynx, and paranasal sinuses, as well as occult primary cancer, salivary gland cancer, and mucosal melanoma (MM). The specific site of disease, stage, and pathologic findings guide treatment (eg, the appropriate surgical procedure, radiation targets, dose and fractionation of radiation, indications for systemic therapy). The NCCN Head and Neck Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel's most recent recommendations regarding management of nasopharynx cancer and ongoing research in this area.},
}

Humans
*Head and Neck Neoplasms/therapy/diagnosis/pathology
Practice Guidelines as Topic
Education, Medical, Continuing

@article {pmid39938467,
year = {2025},
author = {Inaba, H and Teachey, D and Annesley, C and Batra, S and Beck, J and Colace, S and Cooper, S and Dallas, M and Oliveira, S and Kelly, K and Kitko, C and Kohorst, M and Kutny, M and Lacayo, N and Lee-Miller, C and Ludwig, K and Madden, L and Maloney, K and Mangum, D and Massaro, S and McCall, D and Morocco, P and Muller, B and Murphy, L and Nardi, V and Rossoff, J and Schuettpelz, L and Shah, B and Sun, J and Wong, V and Yanik, G and Awotiwon, A and Stehman, K},
title = {Pediatric Acute Lymphoblastic Leukemia, Version 2.2025, NCCN Clinical Practice Guidelines In Oncology.},
journal = {Journal of the National Comprehensive Cancer Network : JNCCN},
volume = {23},
number = {2},
pages = {41-62},
doi = {10.6004/jnccn.2025.0006},
pmid = {39938467},
issn = {1540-1413},
mesh = {Humans ; *Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy/diagnosis/genetics ; Child ; Medical Oncology/standards/methods ; Infant ; },
abstract = {The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pediatric Acute Lymphoblastic Leukemia (ALL) were developed as a result of meetings convened by a multidisciplinary panel of pediatric ALL experts, with the goal of providing recommendations on standard treatment approaches based on current evidence. The NCCN Guidelines for pediatric ALL focus on risk assessment and stratification of risk-adapted therapy; treatment strategies for BCR::ABL1 (Philadelphia chromosome [Ph])-negative and BCR::ABL1-positive B-cell lineage, T-cell lineage, and infant ALL; and supportive care considerations. This selection from the NCCN Guidelines for pediatric ALL focuses on the diagnosis of and management of pediatric T-ALL.},
}

Humans
*Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy/diagnosis/genetics
Child
Medical Oncology/standards/methods
Infant

@article {pmid39938019,
year = {2025},
author = {Chavez, JC and Dickinson, M and Munoz, J and Ulrickson, ML and Thieblemont, C and Oluwole, OO and Herrera, AF and Ujjani, C and Lin, Y and Riedell, PA and Kekre, N and de Vos, S and Wullf, J and Williams, CM and Winters, J and Kloos, IM and Xu, H and Neelapu, SS},
title = {Three-year follow-up analysis of first-line axicabtagene ciloleucel in high-risk large B-cell lymphoma (ZUMA-12).},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2024027347},
pmid = {39938019},
issn = {1528-0020},
abstract = {ZUMA-12 is a multicenter phase 2 study that evaluated axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, as part of first-line treatment in patients with high-risk large B-cell lymphoma (LBCL). In the primary efficacy analysis (n=37; 15.9 months median follow-up), axi-cel demonstrated a high rate of complete responses (CR; 78%) and a safety profile consistent with prior experience. Here, we assessed updated outcomes from ZUMA-12 in 40 treated patients after ≥3 years of follow-up. Eligible adults underwent leukapheresis, followed by lymphodepleting chemotherapy and a single axi-cel infusion of 2×106 CAR T cells/kg. Investigator-assessed CR, objective response, survival, safety, and CAR T-cell expansion were assessed. The CR rate among response-evaluable patients (n=37) increased after the primary analysis to 86% (95% CI, 71-95), with a 92% objective response rate. After a median follow-up of 47.0 months (range, 37.1-57.8), 36-month estimates (95% CI) of duration of response and event-free, progression-free, and overall survival in response-evaluable patients were 81.8% (63.9-91.4), 73.0% (55.6-84.4), 75.1% (57.5-86.2), and 81.1% (64.4-90.5), respectively. In total, 4 patients had new malignancies, 2 occurring after the data cutoff of the primary analysis, none were related to axi-cel. Eight patients died on study, 2 of whom died from non-relapse mortality causes. After ≥3 years of follow-up, axi-cel demonstrated a high cure rate in first-line high-risk LBCL, with no new safety signals after the primary analysis. Further assessments are needed to determine its benefit versus first-line standard-of-care. This trial was registered at clinicaltrials.gov, as #NCT03761056.},
}

@article {pmid39938007,
year = {2025},
author = {Samples, L and Sadrzadeh, H and Frigault, MJ and Jacobson, CA and Hamadani, M and Gurumurthi, A and Strati, P and Shouval, R and Noy, A and Riedell, PA and Dahiya, S and Maloney, DG and Till, BG and Hirayama, AV and Gauthier, J and Gopal, AK and Smith, SD and Poh, C and Lynch, RC and Ujjani, C and Di, M and Raghunathan, V and Shakib-Azar, M and Naresh, KN and Gooley, TA and Yared, JA and Jain, MD and Locke, FL and Leslie, LA and Epperla, N and Ghosh, M and Skarbnik, AP and Hill, BT and Kamdar, M and Ortiz-Maldonado, V and Martínez-Cibrian, N and Shune, L and Shadman, M},
title = {Outcomes Among Adult Recipients of CAR T-cell Therapy for Burkitt Lymphoma.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2024026831},
pmid = {39938007},
issn = {1528-0020},
abstract = {Burkitt lymphoma (BL) is an aggressive B-cell lymphoma associated with poor outcomes in patients with relapsed/refractory disease. This multicenter, retrospective study evaluated real-world CD19 CAR T-cell therapy outcomes in patients with relapsed/refractory BL using data abstracted from the medical records. In total, 31 patients received CAR T-cells after a median of 3 prior therapies (range 1-6). Patients received axi-cel (n = 19), liso-cel (n = 4), tisa-cel (n = 4) or other agents (n = 4). Grade 1-2 CRS occurred in 83.9% of patients (grade ≥3 6.5%), and grade 1-2 ICANS occurred in 29% of patients (grade ≥3 19.4%). Twenty-eight-day mortality was 16.1%, including one patient who died from grade 5 ICANS. The overall response rate at 1 month was 58.0% with a complete response (CR) rate of 41.9%, however the 6-month CR rate was only 25.8%. Median progression-free survival was 2.3 months (95% CI 1.0 - 9.0), and median overall survival was 6.0 months (95% CI 1.9 - 11.5). Three patients (9.7%) received consolidative allogeneic stem cell transplants, but all subsequently relapsed. In conclusion, CD19 CAR T-cell therapy infrequently delivers long term disease control in BL. Further investigation is needed to determine the most effective alternative management of these patients.},
}

@article {pmid39935960,
year = {2025},
author = {Zane, GK and Barbee, LA and Duerr, A and Golden, MR and Manhart, LE and Dimitrov, D and Khosropour, C},
title = {High Incidence and Duration of Antibiotic Use Among a Cohort of Men Who Have Sex With Men in Seattle, Washington.},
journal = {Open forum infectious diseases},
volume = {12},
number = {2},
pages = {ofaf051},
pmid = {39935960},
issn = {2328-8957},
support = {K23 AI113185/AI/NIAID NIH HHS/United States ; },
abstract = {BACKGROUND: Doxycycline postexposure prophylaxis (doxy-PEP) effectively prevents bacterial sexually transmitted infections (STIs) but may increase antibiotic pressure. Little is known about longitudinal antibiotic use among men who have sex with men (MSM), a key population for doxy-PEP.

METHODS: We analyzed data from a prospective cohort of MSM in Seattle, Washington, from 2016 to 2018, prior to the introduction of doxy-PEP. Antibiotic use and reason for prescription were self-reported in weekly surveys and extracted from medical records. We characterized antibiotic use across 49 weeks of follow-up, stratified by specific antibiotics of interest and reasons for prescription. Incidence rates (IRs) were calculated for the number of incident events of antibiotic initiation per 100 person-years (PY) at risk. We assessed factors associated with antibiotic initiation using negative binomial regression to estimate adjusted incidence rate ratios (IRRs).

RESULTS: Among 140 participants, 68.6% (n = 96) received at least 1 antibiotic during follow-up, resulting in an overall IR of 264.5 events of antibiotic initiation per 100 PY and 1696 total days of antibiotic use. STI treatment was the most common reason for antibiotic initiation (IR, 153.5 events per 100 PY; 462 days); however, treatment for other conditions contributed most to overall days of antibiotic use (IR, 42.6 events per 100 PY; 947 days). An age of 25-39 years (IRR, 1.54 [95% confidence interval {CI},
1.02-2.32]) and a history of bacterial STIs <12 months prior to enrollment (IRR, 1.81 [95% CI, 1.12-2.93]) were significantly associated with higher incidence of antibiotic initiation.

CONCLUSIONS: Antibiotic consumption among this population was very high. Our analysis provides a necessary foundation for assessing the potential impacts of doxy-PEP.},
}

@article {pmid39934055,
year = {2025},
author = {Powles, T and Tagawa, S and Vulsteke, C and Gross-Goupil, M and Park, SH and Necchi, A and De Santis, M and Duran, I and Morales-Barrera, R and Guo, J and Sternberg, CN and Bellmunt, J and Goebell, PJ and Kovalenko, M and Boateng, F and Sierecki, M and Wang, L and Sima, CS and Waldes, J and Loriot, Y and Grivas, P},
title = {Sacituzumab govitecan in advanced urothelial carcinoma: TROPiCS-04, a phase III randomized trial.},
journal = {Annals of oncology : official journal of the European Society for Medical Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.annonc.2025.01.011},
pmid = {39934055},
issn = {1569-8041},
abstract = {BACKGROUND: Sacituzumab govitecan (SG), a Trop-2-directed antibody-drug conjugate, demonstrated efficacy and manageable toxicity in the phase II TROPHY-U-01 study in pretreated advanced urothelial carcinoma (aUC). We report the results from final analysis of the global open-label randomized phase III TROPiCS-04 study (NCT04527991) in pretreated aUC.

PATIENTS AND METHODS: Patients with aUC whose disease had progressed on prior platinum-based chemotherapy and checkpoint inhibitor therapy were randomized 1 : 1 to receive SG or treatment of physician's choice (TPC; paclitaxel, docetaxel, or vinflunine). The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS) and objective response rate (ORR) by investigator and blinded independent committee review, as well as safety.

RESULTS: Overall, 711 patients were randomized. After a median follow-up of 9.2 months, the primary endpoint was not met [median OS for SG versus TPC: 10.3 months versus 9.0 months, hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.73-1.02, P = 0.087]. Median PFS with SG and TPC was 4.2 months and 3.6 months, respectively (HR 0.86, 95% CI 0.72-1.03); ORR (95% CI) was 23% (18% to 27%) and 14% (10% to 18%). The most common grade ≥3 treatment-related adverse event (TRAE) with SG was neutropenia (35%, including 12% with febrile neutropenia). Incidence of grade ≥3 TRAEs (67% versus 35%) and grade 5 treatment-emergent adverse events (TEAEs; 7% versus 2%) was higher with SG versus TPC. In the SG group, 16/25 grade 5 TEAEs were infections with neutropenia mostly occurring early in the treatment course of patients with multiple risk factors for febrile neutropenia. Primary prophylactic granulocyte colony-stimulating factor (G-CSF) usage with SG and TPC was 21% and 22%, respectively.

CONCLUSIONS: SG did not result in a significant improvement in OS or PFS compared with TPC in pretreated aUC, although SG activity was demonstrated by a higher ORR. Early toxicity-related complications with SG may have impacted efficacy outcomes.},
}

@article {pmid39932777,
year = {2025},
author = {Patel, SH and Colby, S and Sohal, D and Guthrie, KA and Kachnic, LA and Chiorean, EG and Lowy, AM and Rocha, FG and Hochster, HS and Philip, PA and Ahmad, SA},
title = {Chemotherapy dose density is prognostic for overall survival in patients with resectable pancreas cancer: A landmark analysis of SWOG 1505.},
journal = {Cancer},
volume = {131},
number = {4},
pages = {e35759},
pmid = {39932777},
issn = {1097-0142},
support = {U10 CA180819/CA/NCI NIH HHS/United States ; U10 CA180888/CA/NCI NIH HHS/United States ; U10CA180888/NH/NIH HHS/United States ; U10CA180819/NH/NIH HHS/United States ; },
mesh = {Humans ; *Pancreatic Neoplasms/surgery/mortality/drug therapy/pathology ; Male ; Female ; Aged ; Middle Aged ; *Carcinoma, Pancreatic Ductal/surgery/mortality/drug therapy/pathology ; Prognosis ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Deoxycytidine/analogs & derivatives/administration & dosage/therapeutic use ; Gemcitabine ; Fluorouracil/administration & dosage/therapeutic use ; Adult ; Oxaliplatin/administration & dosage/therapeutic use ; Pancreatectomy ; Leucovorin/administration & dosage/therapeutic use ; },
abstract = {BACKGROUND: Chemotherapy is required to improve the overall survival (OS) of patients with resectable pancreatic ductal adenocarcinoma (PDAC). Assessing the impact of chemotherapy dose density (DD) on survival is difficult as a result of confounding. The objective of this study was to determine the impact of chemotherapy DD on OS in patients with resectable PDAC.

METHODS: This was a secondary analysis of SWOG 1505, a randomized phase 2 trial of perioperative chemotherapy in resectable PDAC. DD was defined as the percentage of chemotherapy dose received of the total planned. Two landmark time points for OS were used: after surgery and at 40 weeks (which encompassed the entire treatment period).

RESULTS: Of the 102 eligible patients enrolled, 73 (71%) underwent surgery, and median preoperative chemotherapy DD was 89%. Patients with ≥85% DD had higher OS compared to those with <85% DD (median, 38.1 vs. 17.2 months; p = .039). Of the 82 patients who survived to 40 weeks postrandomization, 67 underwent surgery, and median DD for all perioperative chemotherapy was 67%. In this cohort, DD ≥70% was associated with better OS (median, 32.2 vs. 14.0 months; p = .017). Perioperative DD was not significantly associated with pathologic response, margin status, or lymph node negativity.

CONCLUSIONS: This is the first study to identify a prognostic association of chemotherapy DD with OS in patients undergoing perioperative chemotherapy and surgery for resectable PDAC. Patients who received ≥85% DD preoperatively and/or ≥70% DD perioperatively survived longer than those receiving a smaller proportion of protocol therapy.},
}

Humans
*Pancreatic Neoplasms/surgery/mortality/drug therapy/pathology
Male
Female
Aged
Middle Aged
*Carcinoma, Pancreatic Ductal/surgery/mortality/drug therapy/pathology
Prognosis
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use
Deoxycytidine/analogs & derivatives/administration & dosage/therapeutic use
Gemcitabine
Fluorouracil/administration & dosage/therapeutic use
Adult
Oxaliplatin/administration & dosage/therapeutic use
Pancreatectomy
Leucovorin/administration & dosage/therapeutic use

@article {pmid39930085,
year = {2025},
author = {Hoffmann, TJ and Graff, RE and Madduri, RK and Rodriguez, AA and Cario, CL and Feng, K and Jiang, Y and Wang, A and Klein, RJ and Pierce, BL and Eggener, S and Tong, L and Blot, W and Long, J and Goss, LB and Darst, BF and Rebbeck, T and Lachance, J and Andrews, C and Adebiyi, AO and Adusei, B and Aisuodionoe-Shadrach, OI and Fernandez, PW and Jalloh, M and Janivara, R and Chen, WC and Mensah, JE and Agalliu, I and Berndt, SI and Shelley, JP and Schaffer, K and Machiela, MJ and Freedman, ND and Huang, WY and Li, SA and Goodman, PJ and Till, C and Thompson, I and Lilja, H and Ranatunga, DK and Presti, J and Van Den Eeden, SK and Chanock, SJ and Mosley, JD and Conti, DV and Haiman, CA and Justice, AC and Kachuri, L and Witte, JS},
title = {Genome-wide association study of prostate-specific antigen levels in 392,522 men identifies new loci and improves prediction across ancestry groups.},
journal = {Nature genetics},
volume = {57},
number = {2},
pages = {334-344},
pmid = {39930085},
issn = {1546-1718},
mesh = {Humans ; Male ; *Genome-Wide Association Study ; *Prostate-Specific Antigen/blood/genetics ; *Prostatic Neoplasms/genetics/ethnology ; *Polymorphism, Single Nucleotide ; Middle Aged ; Aged ; Hispanic or Latino/genetics ; White People/genetics ; Genetic Predisposition to Disease ; Cohort Studies ; },
abstract = {We conducted a multiancestry genome-wide association study of prostate-specific antigen (PSA) levels in 296,754 men (211,342 European ancestry, 58,236 African ancestry, 23,546 Hispanic/Latino and 3,630 Asian ancestry; 96.5% of participants were from the Million Veteran Program). We identified 318 independent genome-wide significant (P ≤ 5 × 10[-8]) variants, 184 of which were novel. Most demonstrated evidence of replication in an independent cohort (n = 95,768). Meta-analyzing discovery and replication (n = 392,522) identified 447 variants, of which a further 111 were novel. Out-of-sample variance in PSA explained by our genome-wide polygenic risk scores ranged from 11.6% to 16.6% for European ancestry, 5.5% to 9.5% for African ancestry, 13.5% to 18.2% for Hispanic/Latino and 8.6% to 15.3% for Asian ancestry and decreased with increasing age. Midlife genetically adjusted PSA levels were more strongly associated with overall and aggressive prostate cancer than unadjusted PSA levels. Our study highlights how including proportionally more participants from underrepresented populations improves genetic prediction of PSA levels, offering potential to personalize prostate cancer screening.},
}

Humans
Male
*Genome-Wide Association Study
*Prostate-Specific Antigen/blood/genetics
*Prostatic Neoplasms/genetics/ethnology
*Polymorphism, Single Nucleotide
Middle Aged
Aged
Hispanic or Latino/genetics
White People/genetics
Genetic Predisposition to Disease
Cohort Studies

@article {pmid39929823,
year = {2025},
author = {Raeisi Dehkordi, S and Wong, IT and Ni, J and Luebeck, J and Zhu, K and Prasad, G and Krockenberger, L and Xu, G and Chowdhury, B and Rajkumar, U and Caplin, A and Muliaditan, D and Gnanasekar, A and Coruh, C and Jin, Q and Turner, K and Teo, SX and Pang, AWC and Alexandrov, LB and Chua, CEL and Furnari, FB and Maciejowski, J and Paulson, TG and Law, JA and Chang, HY and Yue, F and DasGupta, R and Zhao, J and Mischel, PS and Bafna, V},
title = {Breakage fusion bridge cycles drive high oncogene number with moderate intratumoural heterogeneity.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {1497},
pmid = {39929823},
issn = {2041-1723},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; U24 CA264379/CA/NCI NIH HHS/United States ; P50 CA168504/CA/NCI NIH HHS/United States ; R35 CA210057/CA/NCI NIH HHS/United States ; OT2 CA278635/CA/NCI NIH HHS/United States ; R01 GM114362/GM/NIGMS NIH HHS/United States ; OT2 CA278688/CA/NCI NIH HHS/United States ; P01 CA091955/CA/NCI NIH HHS/United States ; CGCATF-2021/100025//Cancer Research UK (CRUK)/ ; },
mesh = {Humans ; *Oncogenes/genetics ; Cell Line, Tumor ; *Gene Amplification ; *Neoplasms/genetics ; Animals ; Mice ; Algorithms ; Genetic Heterogeneity ; Whole Genome Sequencing ; },
abstract = {Oncogene amplification is a key driver of cancer pathogenesis. Both breakage fusion bridge (BFB) cycles and extrachromosomal DNA (ecDNA) can lead to high oncogene copy numbers, but the impact of BFB amplifications on intratumoral heterogeneity, treatment response, and patient survival remains poorly understood due to detection challenges with DNA sequencing. We introduce an algorithm, OM2BFB, designed to detect and reconstruct BFB amplifications using optical genome mapping (OGM). OM2BFB demonstrates high precision (>93%) and recall (92%) in identifying BFB amplifications across cancer cell lines, patient-derived xenograft models, and primary tumors. Comparisons using OGM reveal that BFB detection with our AmpliconSuite toolkit for short-read sequencing also achieves high precision, though with reduced sensitivity. We identify 371 BFB events through whole genome sequencing of 2557 primary tumors and cancer cell lines. BFB amplifications are prevalent in cervical, head and neck, lung, and esophageal cancers, but rare in brain cancers. Genes amplified through BFB exhibit lower expression variance, with limited potential for regulatory adaptation compared to ecDNA-amplified genes. Tumors with BFB amplifications (BFB(+)) show reduced structural heterogeneity in amplicons and delayed resistance onset relative to ecDNA(+) tumors. These findings highlight ecDNA and BFB amplifications as distinct oncogene amplification mechanisms with differing biological characteristics, suggesting distinct avenues for therapeutic intervention.},
}

Humans
*Oncogenes/genetics
Cell Line, Tumor
*Gene Amplification
*Neoplasms/genetics
Animals
Mice
Algorithms
Genetic Heterogeneity
Whole Genome Sequencing

@article {pmid39928955,
year = {2025},
author = {Petty, NE and Radtke, S and Kanestrom, G and Fields, E and Humbert, O and Fiorenza, S and Llewellyn, MJ and Laszlo, GS and Thomas, J and Burger, Z and Swing, K and Zhu, H and Jerome, KR and Turtle, CJ and Walter, RB and Kiem, HP},
title = {Protection of CD33-modified hematopoietic stem cell progeny from CD33-directed CAR T cells in nonhuman primates.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2024015016},
pmid = {39928955},
issn = {2473-9537},
abstract = {The treatment of monogenetic disorders, such as hemoglobinopathies and lysosomal storage diseases, has markedly improved with the advent of cell and gene therapies, particularly allogeneic or gene-modified autologous stem cell transplantations. However, therapeutic efficacy is reliant on maintaining engraftment above a critical threshold. To maintain such engraftment levels, we and others have pursued approaches to shield edited cells from antibody or CAR T-cell mediated selection. Here we focused on CD33, which is expressed early on hematopoietic stem and progenitor cells (HSPC) as well as on myeloid progenitors. Rhesus macaques were engrafted with HSPCs edited to ablate CD33 utilizing either CRISPR/Cas9 or adenine base editor. Both editing strategies showed similar post-transplant recovery kinetics and yielded equivalent levels of engraftment. We then created a V-set domain specific chimeric antigen receptor construct (CAR33), validated its functionality in vitro, and treated both animals with autologous CAR33 T cells. CAR33 T cells expanded after infusion and caused specific depletion of CD33WT but not CD33null progeny - leading to a transient enrichment for gene-edited cells in the blood. No depletion was seen in the bone marrow stem cell compartment with CD34+CD90+ HSCs expressing lower levels of CD33 in comparison to monocytes. Thus, we show proof of concept and safety of an epitope editing based enrichment/protection strategy in macaques.},
}

@article {pmid39928329,
year = {2025},
author = {Henderson, LM and Kim, RY and Tanner, NT and Tsai, EB and Begnaud, A and Dako, F and Gieske, M and Kallianos, K and Richman, I and Sakoda, LC and Schwartz, RG and Yeboah, J and Fong, KM and Lam, S and Lee, P and Pasquinelli, M and Smith, RA and Triplette, M and Tanoue, LT and Rivera, MP},
title = {Lung Cancer Screening and Incidental Findings: A Research Agenda. An Official American Thoracic Society Research Statement.},
journal = {American journal of respiratory and critical care medicine},
volume = {},
number = {},
pages = {},
doi = {10.1164/rccm.202501-0011ST},
pmid = {39928329},
issn = {1535-4970},
support = {K08 CA279881/CA/NCI NIH HHS/United States ; },
abstract = {BACKGROUND: Lung cancer screening with low-dose computed tomography (LDCT) may uncover incidental findings (IFs) unrelated to lung cancer. There may be potential benefits from identifying clinically significant IFs that warrant intervention and potential harms related to identifying IFs that are not clinically significant but may result in additional evaluation, clinician effort, patient anxiety, complications, and excess cost.

OBJECTIVES: To identify knowledge and research gaps and develop and prioritize research questions to address the approach to and management of IFs.

METHODS: We convened a multidisciplinary panel to review the available literature on IFs detected in lung cancer screening LDCT exams, focusing on variability and standardizing reporting, management of IFs, and evaluation of the benefits and harms of IFs, particularly cardiovascular-related IFs. We used a three-round modified Delphi process to prioritize research questions.

RESULTS: This statement identifies knowledge gaps in (1) reporting of IFs, (2) management of IFs, and (3) identifying and reporting coronary artery calcification found on lung cancer screening LDCT. Finally, we present the panel's initial 36 research questions and the final 20 prioritized questions.

CONCLUSIONS: This statement provides a prioritized research agenda to further efforts focused on evaluating, managing, and increasing awareness of IFs in lung cancer screening.},
}