@article {pmid41152111,
year = {2025},
author = {Jindal, T and Jiang, CY and Alhalabi, O and Davidsohn, M and Freeman, D and Epstein, IY and Bakaloudi, DR and Talukder, R and Nizam, A and Nguyen, CB and Oh, E and Tsung, I and Glover, MJ and Khaki, AR and Taylor, AK and Jaime-Casas, S and Jang, A and Lemke, E and Pywell, C and Evans, ST and Shin, D and Bilen, MA and Basu, A and Kilari, D and Tripathi, A and Brown, J and Emamekhoo, H and Davis, NB and Shah, S and Gupta, S and Grivas, P and Bellmunt, J and Alva, A and Campbell, MT and Koshkin, VS},
title = {Efficacy of sacituzumab govitecan after enfortumab vedotin in advanced urothelial carcinoma: Analysis of the UNITE study.},
journal = {Urologic oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.urolonc.2025.09.025},
pmid = {41152111},
issn = {1873-2496},
abstract = {BACKGROUND: Sacituzumab govitecan (SG) is an antibody-drug conjugate used for advanced urothelial carcinoma (aUC) refractory to platinum-based chemotherapy and immune checkpoint inhibitors (ICI). Real-world data are needed to better define SG outcomes, particularly following treatment with enfortumab vedotin (EV). In this analysis, we aim to evaluate efficacy of SG after EV and assess putative biomarkers associated with outcomes.

METHODS: In the UNITE retrospective study, we identified patients who received ≥1 SG cycle after therapy with EV. Observed response rate (ORR) was assessed in evaluable patients and correlated with baseline clinical characteristics and biomarkers. ORRs were compared using logistic regression, while progression free survival (PFS) and overall survival (OS) from SG start were estimated via Kaplan-Meier and Cox proportional hazard (PH) model. Biomarkers of response were evaluated in multivariate Cox PH models after accounting for relevant clinical variables.

RESULTS: Among 107 patients treated with SG after EV, 97 (91%) had NGS data. Median age was 69 years, 73% were male, 33% had ≥4 prior lines of therapy, and 42% received G-CSF. ORR was 18% (95% CI: 10%-26%), median PFS 3.2 months, and median OS 6.0 months. In patients with disease control on EV, ORR was 22% compared to 8% in primary progressors on EV. No significant associations were found between molecular biomarkers and SG outcomes in the multivariate analysis.

CONCLUSION: SG showed modest activity after EV in heavily pretreated patients with aUC. ORR with SG after EV was lower than reported in phase 2 and phase 3 clinical trials for SG in the postplatinum/ICI setting.},
}

@article {pmid41149505,
year = {2025},
author = {Rios-Doria, E and Reichel, JB and Radke, MR and Manhardt, E and Rubin-Saika, M and Lockwood, C and Swisher, EM and Banda, K},
title = {Dynamic Monitoring of Recurrent Ovarian Cancer Using Serial ctDNA: A Real-World Case Series.},
journal = {Current oncology (Toronto, Ont.)},
volume = {32},
number = {10},
pages = {},
pmid = {41149505},
issn = {1718-7729},
support = {0000//Brotman Baty Institute/ ; },
mesh = {Humans ; Female ; *Ovarian Neoplasms/genetics/blood/pathology ; *Circulating Tumor DNA/blood/genetics ; *Neoplasm Recurrence, Local/blood/genetics ; Middle Aged ; Aged ; *Biomarkers, Tumor/blood/genetics ; Adult ; CA-125 Antigen/blood ; },
abstract = {Recurrent ovarian cancer (OC) is challenging to detect early using current methods like CA-125 and imaging. Circulating tumor DNA (ctDNA) may improve disease monitoring. Here, we assess the real-world clinical utility of serial ctDNA analyses in patients with recurrent OC. We analyzed serial plasma samples (N = 23) from six patients with recurrent OC using a tumor-informed next-generation sequencing assay targeting 68 cancer-related genes developed at the University of Washington. ctDNA variant allele frequencies (VAFs) were correlated with CA-125 levels, radiographic findings, and clinical outcomes. ctDNA levels generally reflected clinical status, accurately mirroring disease progression and therapeutic response. In one patient, rising ctDNA preceded clinical recurrence by four months, despite normal CA-125 and imaging, highlighting its potential advantage. Conversely, some patients exhibited clinical progression with undetectable ctDNA, indicating limitations in assay sensitivity, biological factors, or metastatic sites (e.g., brain metastases). ctDNA and CA-125 showed complementary value in most cases, suggesting potential combined use in clinical monitoring. Our findings demonstrate that ctDNA is a promising biomarker to complement existing monitoring approaches for recurrent OC. In some cases, capable of predicting relapse and treatment response ahead of current clinical indicators. However, identified discordances underscore technical and biological challenges that warrant further investigation. Larger prospective studies are necessary to refine ctDNA's clinical utility and integration into personalized OC care.},
}

Humans
Female
*Ovarian Neoplasms/genetics/blood/pathology
*Circulating Tumor DNA/blood/genetics
*Neoplasm Recurrence, Local/blood/genetics
Middle Aged
Aged
*Biomarkers, Tumor/blood/genetics
Adult
CA-125 Antigen/blood

@article {pmid41147516,
year = {2025},
author = {Thomas, AB and Matthews, AL and Brooks, O and Winquist, A and Nelson, LA and Arias-Fontenot, R and Buchwald, D and Casaletto, KB and Weintraub, S and Heaton, RK and French, BF and Suchy-Dicey, A and Barbosa-Leiker, C},
title = {Psychometric properties of the NIH Toolbox Cognition Battery composites in older adults at risk for Alzheimer's disease and related dementias: A systematic review.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21},
number = {10},
pages = {e70673},
pmid = {41147516},
issn = {1552-5279},
support = {1RF1AG071677-01//National Institute of Health/National Institute on Aging/ ; },
mesh = {Humans ; *Alzheimer Disease/diagnosis/psychology ; *Psychometrics ; United States ; National Institutes of Health (U.S.) ; *Neuropsychological Tests ; *Dementia/diagnosis/psychology ; Aged ; *Cognition ; },
abstract = {This systematic review evaluated the psychometric performance of the National Institutes of Health's Toolbox Cognition Battery (NIHTB-CB) composite scores in older adults with and without Alzheimer's disease and related dementias (ADRD). A systematic literature search was conducted using MEDLINE, Embase, PsycINFO, and CINHAL databases. The evidence quality of NIHTB-CB measurement properties was assessed using integrated Consensus-based Standards for the Selection of Health Measurement Instrument (COSMIN) methodology and the Interpretation/Use Argument framework. Fourteen studies met inclusion criteria for this review of the NIHTB-CB. Evidence supporting the scoring, generalization, and extrapolation inferences of the Total, Crystallized, and Fluid composite scores in older adults ranged from developing through exemplary ratings. Findings indicate additional research is warranted on the NIHTB-CB in older adult and ADRD populations. The present study highlights the importance of continued use and research of the NIHTB-CB in diverse, older populations who are at risk for ADRD. HIGHLIGHTS: Limited research focuses on the National Institutes of Health's Toolbox Cognition Battery (NIHTB-CB) composites in older adults. The general psychometric robustness of the NIHTB-CB has been es. The Crystallized composite shows proficient psychometric evidence. The psychometric evidence of Fluid composite is developing due to limited data.},
}

Humans
*Alzheimer Disease/diagnosis/psychology
*Psychometrics
United States
National Institutes of Health (U.S.)
*Neuropsychological Tests
*Dementia/diagnosis/psychology
Aged
*Cognition

@article {pmid41146877,
year = {2025},
author = {Kuhlmann, AS and Madkhali, N and Moskovitz, E and Parrott, JE and Raman, SS and Riker, AO and Martinez-Reyes, J and Gupta, M and Jang, RA and Nelson, V and Gray, MD and Taylor, JJ and Peterson, CW and Kiem, HP},
title = {Heavy-chain immunoglobulin locus editing in rhesus macaque B cells to confer antibody production.},
journal = {Molecular therapy. Methods & clinical development},
volume = {33},
number = {4},
pages = {101598},
pmid = {41146877},
issn = {2329-0501},
abstract = {Antibody-based immunotherapies are promising; however, their application remains limited to acute diseases due to rapid clearance of antibodies in vivo. Some chronic conditions could benefit from sustained therapeutic antibody expression. One such instance is human immunodeficiency virus type 1 (HIV-1), where the efficiency of broadly neutralizing antibodies by passive immunization has been limited in clinical trials. B cell editing to enable sustained production of an antibody of interest in vivo could address this issue. However, the long-term potential of this approach and feasibility to perform editing in B cells from people living with HIV remain to be determined. We investigated editing of rhesus macaque B cells from healthy or simian/human immunodeficiency virus (SHIV)-infected animals to model this approach. An antibody-encoding cassette was inserted in the immunoglobulin locus by CRIPSR-Cas9-mediated ex vivo B cell editing. Similar indel efficiencies were achieved in B cells from both uninfected and infected animals, and expression of the antibody of interest was detected in up to 10% of uninfected B cells. This study paves the way for future in vivo work to assess the long-term potential of this approach and its impact on B cell development and function in an immunocompetent in vivo nonhuman primate model of HIV persistence and cure.},
}

@article {pmid41145253,
year = {2025},
author = {Kataria, I and Selmouni, F and Duggan, C and Sullivan, R and Purushotham, A and Sankaranarayanan, R and Taghavi, K and Basu, P},
title = {Application of implementation science methods and theories for cancer control planning in low-income and middle-income countries: a scoping review.},
journal = {BMJ open},
volume = {15},
number = {10},
pages = {e108755},
doi = {10.1136/bmjopen-2025-108755},
pmid = {41145253},
issn = {2044-6055},
mesh = {Humans ; *Neoplasms/prevention & control/therapy ; *Developing Countries ; *Implementation Science ; Health Policy ; Delivery of Health Care/organization & administration ; *Health Planning ; },
abstract = {INTRODUCTION: Implementation science (IS) is increasingly recognised as vital in cancer control planning and integrating evidence-based interventions across the cancer care continuum. Contextual differences often cause variability in delivering optimised healthcare, which IS approaches could mitigate. While IS improves planning effectiveness, many programme and policy planners remain unaware of its benefits. To address this, we examined IS theories applied to national cancer control plans (NCCPs)/strategies across five domains: stakeholder engagement, situational analysis, capacity assessment, economic evaluation and impact assessment.

METHODS: We conducted a scoping review using the Arksey and O'Malley framework to analyse NCCPs and strategies from 16 and 17 countries belonging to low and medium categories of Human Development Index (HDI), focusing on resource-constrained settings. We identified plans through the International Cancer Control Partnership portal, categorised them by WHO region and included only those available in English or French. We extracted data into a Microsoft Excel database and performed thematic analysis across five IS domains. Multiple IS experts, selected purposively based on their familiarity with resource-constrained settings, validated the findings, assessed policy relevance and helped develop a pathway for integrating IS into national cancer control planning. They reviewed structured questions in advance and provided feedback on analyses, practical utility, dissemination and simplifying IS application, which was used to refine the pathway and reach consensus.

RESULTS: While many NCCPs incorporated key IS elements such as stakeholder engagement, situational analysis and impact measurement, these often needed to be more explicit and consistently applied. None of the plans assessed health system capacity to determine readiness for implementing new interventions. Although most plans described stakeholder engagement, it was typically unstructured and incomplete. Four low HDI and nine medium HDI countries included costed plans, generally using an activity-based approach. All plans included impact measures (eg, key performance indicators), but five lacked mechanisms for engaging stakeholders or responsible entities to achieve the targets. These findings informed a proposed pathway to integrate IS principles into cancer control planning.

CONCLUSION: Integrating IS into national cancer control planning offers a structured framework for achieving equitable and feasible cancer control policies, particularly in resource-constrained settings, by enabling realistic goal setting and benchmarking against regional and global standards.},
}

Humans
*Neoplasms/prevention & control/therapy
*Developing Countries
*Implementation Science
Health Policy
Delivery of Health Care/organization & administration
*Health Planning

@article {pmid41143136,
year = {2025},
author = {Tanaka, K and Chikowore, TJB and Deeks, SG and Estes, JD and Ho, YC and Jiang, S and Lee, MJ and Li, C and Machinda, A and Martins, M and Mdletshe, P and Ndhlovu, ZM and Neogi, U and Ott, MM and Rasmussen, TA and Reddy, K and Rutishauser, RL and Farrell-Sherman, A and Tiemessen, CT and Voss, JE and Kityo, C and Lewin, SR and Ndung'u, T and McCune, JM},
title = {Meeting Summary for Keystone Symposia on HIV Cure: Antiretroviral Therapy (ART)-Free Control of HIV Infection in Durban, South Africa, 2025.},
journal = {Pathogens & immunity},
volume = {10},
number = {2},
pages = {196-229},
pmid = {41143136},
issn = {2469-2964},
abstract = {Antiretroviral therapy (ART) can effectively control human immunodeficiency virus (HIV) replication; however, lifelong treatment is required due to viral reservoirs, which fuel viral rebound. This necessitates curative interventions that can achieve either eradication of the reservoir or durable remission off ART. Advances in technology have fostered development of multi-omic techniques encompassing molecular tools, proteomic analyses, imaging, and artificial intelligence (AI)-driven data analysis to understand HIV reservoir biology and persistence. These have informed the investigation of therapeutic interventions such as broadly neutralizing antibodies, latency reversal, immune cell augmentation, antivirals, and gene therapy. From April 7-10, 2025, experts in the field convened at the Keystone Symposia conference, HIV Cure: Antiretroviral Therapy (ART)-Free Control of HIV Infection in Durban, South Africa, to discuss novel strategies for eradication and/or durable ART-free control of HIV.},
}

@article {pmid41141451,
year = {2025},
author = {Reed, JC and Hall, L and McKhann, A and Kwak, G and Goecker, EA and Coombs, RW and Chen, H and Roa, J and Vecchio, A and Daar, ES and Hunt, PW and Marra, CM and Campbell, TB and Ma, Q and Swaminathan, S and Macatangay, BJC and Morse, GD and Miller, T and Rusin, D and Ha, B and Alston-Smith, B and Paul, R and Letendre, SL and Spudich, SS and Greninger, AL},
title = {Antiretroviral Therapy Intensification With Dolutegravir and/or Maraviroc Did Not Affect HIV-1 Cell-Associated DNA, RNA, and 2--LTR Circles Over 12 Weeks.},
journal = {Open forum infectious diseases},
volume = {12},
number = {10},
pages = {ofaf594},
pmid = {41141451},
issn = {2328-8957},
abstract = {BACKGROUND: Neurocognitive impairment (NCI) among people living with human immunodeficiency virus (HIV; PWH) on antiretroviral therapy (ART) may result from residual viral replication. The A5324 trial found that ART intensification with dolutegravir (DTG) with or without maraviroc (MVC) did not affect NCI in PWH. We evaluated the impact of ART intensification on peripheral virological measures during the first 12 weeks of intensification.

METHODS: The A5324 study was a randomized, double-blind, placebo (PBO)-controlled, 96-week trial of ART intensification with either dual PBO, DTG + PBO, or DTG + MVC in PWH with NCI on ART who were naive to integrase strand transfer inhibitors and MVC. At baseline and weeks 2, 4, and 12, HIV-1 RNA was measured in plasma with a low-copy assay, while HIV-1 cell-associated DNA (caDNA), cell-associated unspliced RNA (caRNA), and cell-associated 2-long terminal repeat circles (ca2LTR) were quantified from peripheral blood mononuclear cells using droplet digital polymerase chain reaction.

RESULTS: Of the 171 participants, 59 were randomized to dual PBO, 57 to DTG + PBO, and 55 to DTG + MVC. Changes in caDNA and caRNA and detection of plasma RNA did not differ between treatment arms over 12 weeks (P > 0.05). Detection of ca2LTR was less frequent at weeks 2-4 in the DTG + MVC arm (40.4%) than in the dual-PBO (70.7%; P =0 .02) and DTG + PBO (68.4%; P = 0.03) arms. However, this difference diminished by week 12, and baseline ca2LTR detection in the DTG + MVC arm was lower than in the other groups.

CONCLUSIONS: DTG intensification had no effect on peripheral markers of HIV-1 persistence. DTG + MVC intensification reduced ca2LTR detection at weeks 2-4, though this effect did not persist through week 12. These findings indicate the minimal impact of intensification on the HIV-1 peripheral reservoir, consistent with prior studies.},
}

@article {pmid41141393,
year = {2026},
author = {Choudhury, SR and Kaushal, A and Biswas, P and Padilla, C and Sarthy, JF and Chavan, A and Gonzalez, GA and Meshinchi, S and Farrar, JE},
title = {Transcriptional rewiring by enhancer methylation in CBFA2T3-GLIS2-driven pediatric acute megakaryoblastic leukemia.},
journal = {Genes & diseases},
volume = {13},
number = {1},
pages = {101843},
pmid = {41141393},
issn = {2352-3042},
abstract = {Resistance to chemotherapy and subsequent relapse remain the primary challenge in pediatric acute myeloid leukemia (pAML), particularly in CBFA2T3-GLIS2 (C/G) fusion-positive acute megakaryoblastic leukemia. Here we demonstrate that the C/G fusion drives extensive DNA methylation changes and oncogenic enhancer activation at cis-regulatory elements (CREs), reshaping gene expression. This multi-omics analysis reveals a distinct hypermethylation pattern at promoters of up-regulated genes in C/G[+] pAML across patient samples (n = 24) and representative cell lines, notably enriched in adhesion-related, TGFβ, or Wnt signaling pathways. Hypermethylated regions adjacent to transcription start sites (TSS) maintain open chromatin with H3K27ac enrichment, supporting a mechanism of de novo chromatin looping and active transcription in a non-canonical manner. Additionally, C/G fusion binding near the DNA methyltransferase 3B (DNMT3B) promoter correlates with elevated DNMT3B expression, implicating its role in aberrant DNA methylation changes at CREs. This study elucidates the epigenetic mechanisms driving C/G[+] pAML, showing how the fusion reshapes chromatin and DNA methylation landscapes by impacting the expression (and likely activity) of epigenetic modifiers like DNMT3B. Functionally, DNMT3B inhibition enhances apoptotic sensitivity to BCL2 blockade, indicating that targeting DNMT3B may overcome apoptotic resistance in C/G[+] leukemic cells and offer a therapeutic strategy for this high-risk subtype.},
}

@article {pmid41141367,
year = {2025},
author = {Wick, BJ and Kluesner, MG and Slipek, NJ and Skeate, JG and Niemeyer, EM and Webber, BR and Moriarity, BS},
title = {Installation of dominant-negative mutations in FAS and TGFβR2 via base editing in primary T cells.},
journal = {Molecular therapy. Oncology},
volume = {33},
number = {4},
pages = {201063},
pmid = {41141367},
issn = {2950-3299},
abstract = {Adoptive cell transfer (ACT) of engineered T cells is effective against B cell malignancies but has faltered against solid tumors due to the immunosuppressive tumor microenvironment (TME). FAS ligand (FASL) and transforming growth factor β (TGF-β) are key mediators of T cell dysfunction in the TME and overexpressing dominant negative (dn) forms of their receptors in T cells increases anti-tumor efficacy in solid tumor models. However, an approach that directly targets the endogenous genes would be more amenable to multiplex editing and reduce competition with WT alleles. Here, we employ base editing (BE) in primary human T cells to install naturally occurring dominant negative FAS and TGFβR2 mutations. In vitro survival and proliferation assays demonstrate that BE T cells are resistant to pro-apoptotic and anti-proliferative effects of FAS and TGF-β signaling. Chimeric antigen receptor (CAR)-T cells with BE-installed dn TGFβR2 or dn FAS exhibit improvements in cytotoxicity, while dn TGFβR2 CAR T demonstrate increased persistence and reduced expression of phenotypic markers of exhaustion compared to controls. Moreover, BE-engineered dn CAR T outperform lentiviral-engineered cDNA over expression counterparts in several functional assays. Considering the efficiency of BE and its amenability for multiplex editing, our approach lends itself to engineering strategies necessary to overcome T cell dysfunction in solid tumors.},
}

@article {pmid41138914,
year = {2025},
author = {Zhang, Y and Alver, S and Shan, Z and Mossavar-Rahmani, Y and Hu, J and Zhang, J and St-Onge, MP and Kaplan, R and Xue, X and Qi, Q},
title = {The timing of macronutrient and major food group intake and associations with mortality among US adults, 1999-March 2020: a serial cross-sectional study.},
journal = {The American journal of clinical nutrition},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajcnut.2025.10.014},
pmid = {41138914},
issn = {1938-3207},
abstract = {BACKGROUND: Eating timing has been increasingly linked to health, yet national trends in macronutrient/food group timing and their health implications remain unclear.

OBJECTIVE: To characterize trends in timing of energy, macronutrient, and food group intake among US adults and examine their associations with mortality.

METHODS: In this serial cross-sectional study of adults aged ≥20 years with ≥1 valid 24-hour dietary recall (National Health and Nutrition Examination Survey, 1999-March 2020), we examined secular trends in timing of energy, macronutrients, and major food group intake. Associations with mortality (through December 2019) were examined using Cox models.

RESULTS: Among 50,264 adults, evening (6-10pm) accounted for the highest daily energy intake (weighted mean proportions across years, 31.9%-33.3%), followed by noon (10am-2pm, 24.7%-26.8%), afternoon (2-6pm, 19.9%-21.8%), morning (6-10am, 13.5%-14.9%), and overnight (10pm-6am, 5.6%-6.5%); midnight (10-2am) eating occurred in 23.4%-28.0% of the population. Macronutrient and food groups followed similar patterns, except whole grain (peaked in the morning) and fruit, egg, and dairy intake (more evenly distributed). Over years, noon and midnight energy intake proportions declined, while afternoon proportion increased; secular trends varied by macronutrients/food groups. Fasting started at 8:34-8:51pm and ended at 8:41-8:52am; intake midpoint was 2:38-2:48pm; intake duration was 11.9-12.2 hours. Male, non-Hispanic black, and socioeconomically disadvantaged groups had greater midnight intake proportions and later intake midpoints. Reallocating 5% of daily energy to midnight was associated with higher cardiovascular mortality (HR, 1.09; 95% CI, 1.02,1.17), driven by carbohydrates; reallocating 5% to predawn (2-6am) was associated with higher cancer mortality (1.22;1.05,1.41), driven by proteins. Each 1-hour delay in fasting and intake midpoint was associated with an 8%-9% higher cardiovascular mortality.

CONCLUSION: Overnight intake and delayed eating timing are prevalent among US adults, especially among socioeconomically disadvantaged groups, and were associated with higher mortality, particularly for specific macronutrients/foods, supporting eating timing recommendations integrating food composition.},
}

@article {pmid41138816,
year = {2025},
author = {Shadman, M and Ahmed, S and Byrne, MT and Chavez, JC and Kamdar, M and Sorror, ML and Perales, MA and Hill, JA and Moslehi, J and Miklos, DB},
title = {Who Is Eligible for CAR T-Cell Therapy? Expert Perspectives on Overcoming Referral Barriers.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.10.025},
pmid = {41138816},
issn = {2666-6367},
abstract = {BACKGROUND: CD19-directed chimeric antigen receptor (CAR) T-cell therapies, including lisocabtagene maraleucel, axicabtagene ciloleucel, and tisagenlecleucel, have revolutionized the treatment landscape for patients with hematologic malignancies. However, identification and referral of patients who could benefit from treatment remains a significant challenge.

OBJECTIVE: To report expert recommendations for CAR T-cell therapy referral.

METHODS: Recommendations were gathered from 10 experts in oncology, hematology, cardiology, and infectious disease from a roundtable meeting and/or subsequent reviews from November 13, 2024, to June 9, 2025.

RESULTS: The authors considered the following potential factors: age, performance status, disease status, cardiovascular function, pulmonary function, renal function, hepatic function, infections, and psychological health. Based on existing evidence, the authors agreed that none of the factors discussed should preclude patients from receiving referrals/further evaluation for CAR T-cell therapy, particularly with current advances in supportive care and integration of services from other specialties. Timely referral should be made by the patient's primary oncologist to specialists as early as the disease is deemed relapsed or refractory, and preferably before the subsequent line of therapy is started to allow better access to care and to improve treatment outcomes. Before CAR T-cell therapy, holding therapy (before leukapheresis) and/or bridging therapy (after leukapheresis) may be given to patients with high-volume disease, in consultation with CAR T-cell therapy specialists. Based on the safety profile of CAR T-cell therapies, experts recommended flexible monitoring and transfer of care back to primary/community oncology physicians, starting from 2 weeks after infusion to improve access to this potentially curative therapy. Adaptations to clinical practice based on the most recent regulations, policy requirements, and institutional guidelines should be made as needed.

CONCLUSIONS: In summary, a panel of 10 experts provided recommendations for timely patient referral for CAR T-cell therapy upon occurrence of relapsed or refractory disease and before initiation of subsequent line of therapy to improve care access and treatment outcomes. Experts noted that with close collaboration between CAR T-cell therapy specialists and other medical disciplines, CAR T-cell therapy remains a feasible option for most patients despite their comorbidities.},
}

@article {pmid41138741,
year = {2025},
author = {Anderson, BO and Duggan, C},
title = {Lessons from CONCORD and VENUSCANCER: closing global gaps in cancer care for women.},
journal = {Lancet (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.1016/S0140-6736(25)01580-6},
pmid = {41138741},
issn = {1474-547X},
}

@article {pmid41137757,
year = {2025},
author = {Fong, Y and Huang, Y and Huang, Y and Woo, W and McGarry, A and Áñez, G and Dunkle, LM and Cho, I and Houchens, CR and Martins, K and Jayashankar, L and Castellino, F and Petropoulos, CJ and Leith, A and Haugaard, D and Webb, W and Lu, Y and Yu, C and Carpp, LN and Randhawa, AK and Andrasik, MP and Kublin, JG and Hutter, J and Keshtkar-Jahromi, M and Beresnev, TH and Rodriguez, CA and Tapia, M and Turley, CB and Zorrilla, CD and Cohen, SH and Kline, SE and Barranco, E and Corey, L and Neuzil, KM and Follmann, D and Ake, JA and Gay, CL and Kotloff, KL and Jones, T and Koup, RA and Donis, RO and Gilbert, PB},
title = {Analysis of antibody markers as immune correlates of risk of severe COVID-19 in the PREVENT-19 efficacy trial of the NVX-CoV2373 recombinant protein vaccine.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {},
number = {},
pages = {},
doi = {10.1093/cid/ciaf558},
pmid = {41137757},
issn = {1537-6591},
abstract = {BACKGROUND: We previously showed that ancestral-specific anti-Spike binding IgG concentration and 50% inhibitory dilution neutralizing antibody titer (nAb-ID50) measured at 2 weeks post-dose 2 (∼peak) were inverse correlates of risk (CoRs) of COVID-19 over 2 months post ∼peak in the PREVENT-19 trial of the NVX-CoV2373 vaccine; there were not sufficient data to assess CoRs of severe COVID-19.

METHODS: Here we assessed, in the same vaccinated cohort, Delta- and ancestral-specific Spike IgG and nAb-ID50 at ∼peak and over time as CoRs of severe COVID-19 and of Delta COVID-19 over 3.5-10 months post ∼peak (287 breakthrough Delta cases, including 8 severe; 446 non-cases).

RESULTS: ∼Peak antibody levels were much higher for non-cases vs. severe cases (all inferred Delta), with nAb-ID50 Delta geometric mean 209.5 arbitrary units (AU)/mL (95% CI: 176.1, 249.1) vs. 9.6 AU/mL (95% CI: 2.4, 38.6), respectively. Frequency of detectable nAb-ID50 titer was 98.3% (97.2, 99.0) for non-cases vs. 62.5% (22.3, 93.9) for severe cases. All markers were inverse CoRs of severe COVID-19, with a ∼peak hazard ratio (HR) of 0.13 (95% CI: 0.03, 0.57) per 10-fold nAb-ID50 Delta increase. Severe COVID-19 risk through 305 days post-Day 35 was 0.0338 (0.0043, 0.206) at the nAb-ID50 Delta 2.5th percentile (8.4 AU/ml), and 0.002 (0.0000, 0.0108) and 0.0002 (0.0000, 0.0035) at the 50th and 95th percentiles (210, 2522 AU/ml).

CONCLUSIONS: Post-vaccination NVX-CoV2373 antibody levels are stronger predictors of severe COVID-19 than any-severity Delta COVID-19. Low antibody responses indicate vulnerability to severe COVID-19.},
}

@article {pmid41136629,
year = {2025},
author = {Corey, L and Ratevosian, J and Beyrer, C and Currier, J and Eron, J and Cohen, MS and Deeks, SG},
title = {How HIV research drives health innovation in multiple diseases.},
journal = {Nature medicine},
volume = {},
number = {},
pages = {},
pmid = {41136629},
issn = {1546-170X},
support = {UM1 AI068614/AI/NIAID NIH HHS/United States ; UM1AI068636//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; UM1AI068636//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; UM1AI068619//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; },
}

@article {pmid41136348,
year = {2025},
author = {Duran, MC and Shah, PD and Bell-Brown, AM and Rojina, J and Glascock, M and Ramirez, M and Ibarra, G and Garza, L and Linde, S and Bishop, S and Garrison, MM and Pascoe, KM and Drain, PK and Zhou, C and Ko, LK},
title = {Back to school: a qualitative study evaluating a community-informed COVID-19 risk communication intervention for rural elementary school children and their families.},
journal = {Translational behavioral medicine},
volume = {15},
number = {1},
pages = {},
pmid = {41136348},
issn = {1613-9860},
support = {OT2 HD107544/GF/NIH HHS/United States ; },
mesh = {Humans ; *COVID-19/prevention & control ; Child ; Qualitative Research ; Female ; Male ; Rural Population ; Focus Groups ; Schools ; Parents/psychology ; SARS-CoV-2 ; *Students/psychology ; *Return to School ; Communication ; School Health Services ; Health Knowledge, Attitudes, Practice ; Adult ; },
abstract = {BACKGROUND: ReOpening Schools Safely and Educating Youth (ROSSEY) was a cluster randomized controlled trial of a risk communication intervention for COVID-19 prevention to promote safe return to school among students in a rural, agricultural community.

PURPOSE: This qualitative study evaluated the implementation of a risk communication intervention and a school district's COVID-19 testing program through parent focus groups and interviews with school staff and students.

METHODS: Parents (n = 37), students (n = 19), and school staff (n = 14) from seven schools that received the intervention shared their experience via focus groups and interviews informed by the RE-AIM framework. Deductive and inductive coding was conducted by four data analysts. Themes were validated with community members.

RESULTS: Parent focus groups, student and staff interviews provided insight into the ROSSEY study implementation. We identified five main themes: (i) social and financial drivers of participation; (ii) personal beliefs and unique challenges to research participation; (iii) intervention reinforced knowledge and shifted behavior; (iv) the appeal of comic books and videos supported adoption; and (v) multimodal communication and partnerships enhanced implementation.

CONCLUSIONS: The risk communication intervention was deemed culturally appropriate, reinforced previous knowledge, and encouraged adoption of preventive behaviors. The partnership with the school district and collaboration with the district's COVID-19 testing program ensured success of recruitment, study implementation, and adoption of preventive behaviors.},
}

Humans
*COVID-19/prevention & control
Child
Qualitative Research
Female
Male
Rural Population
Focus Groups
Schools
Parents/psychology
SARS-CoV-2
*Students/psychology
*Return to School
Communication
School Health Services
Health Knowledge, Attitudes, Practice
Adult

@article {pmid41135920,
year = {2025},
author = {Medlin, AR and Abrams, HR and Kent, EE and Ogunjesa, BA and Park, S and Tan, KR},
title = {Variations in mental distress among caregivers of individuals with chronic illnesses and comorbid cognitive impairment.},
journal = {American journal of preventive medicine},
volume = {},
number = {},
pages = {108165},
doi = {10.1016/j.amepre.2025.108165},
pmid = {41135920},
issn = {1873-2607},
abstract = {OBJECTIVES: To examine rates of mentally unhealthy days (MUDs) and frequent mentally unhealthy days (FMUDs) among caregivers of cancer, heart disease, mental illness, and ADRD based on caregiving intensity, and how cognitive impairment (CI) in non-ADRD caregiving moderates these relationships.

METHODS: Data from 22,550 caregivers in the 2019-2023 Behavioral Risk Factor Surveillance System were used to explore the relationship between caregiving intensity, MUDs, and the presence of CI. Zero-inflated negative binomial regressions assessed associations of caregiving intensity on MUDs, and logistic regressions examined patterns in FMUDs, controlling for demographics and survey weighting.

RESULTS: Caregivers of individuals with mental illness reported the highest FMUDs (27.53%) followed by cancer (20.3%), heart disease (18.57%), and ADRD (17.82%). Increased caregiving intensity correlated with higher MUD rates, particularly among cancer, heart disease, and ADRD caregivers. Cancer caregivers showed increased MUDs when moderating for CI. Higher caregiving intensity was linked to increased FMUDs in cancer and ADRD caregivers, with cancer caregivers showing more FMUDs when moderating for CI.

CONCLUSIONS: Caregiving intensity affects mental health outcomes differently across illnesses. Tailored support is needed for caregivers, especially those providing care for individuals with comorbid cognitive impairment.},
}

@article {pmid41135058,
year = {2025},
author = {Adesina, O and Voutsinas, JM and Wu, QV and Teos, LY and Rokni, M and Nalbant, H and Nardo, L and Wun, T and Zemel, BS},
title = {Low bone mineral density and pain impact in adults with sickle cell disease.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025015957},
pmid = {41135058},
issn = {2473-9537},
abstract = {Low bone mineral density (BMD) is prevalent skeletal finding in people with sickle cell disease (SCD), but its clinical consequences are poorly understood. We hypothesized that low BMD, independent of osteonecrosis (ON), would associate with worse pain in SCD adults. In the SCD Bone Pain study, 53 ambulatory adults (64% females, mean age 38±11years, 66% Hb SS/Sβ0 thalassemia) underwent dual-energy X-ray absorptiometry (DXA) scans of the lumbar spine, hip, forearm, and whole body. They also completed the Adult Sickle Cell Quality of Life Measurement Information System pain impact questionnaire. Twenty-three participants (43%) had low bone mass, defined as lumbar spine, total hip, or femoral neck BMD Z-scores ≤ -2. In multivariate linear regression, lumbar spine BMD Z-scores significantly changed by +0.31, -0.29, -0.14, and -1.3 for every unit increase in hemoglobin, indirect bilirubin, and white blood cell count, and with Crizanlizumab use, respectively. Pain impact T-scores significantly decreased (worsened) by 6.0 and 6.5 with reduced estimated glomerular filtration rate and chronic opioid therapy, respectively, but increased (improved) by 3.8 for every unit increase in serum phosphate. Median [interquartile range] pain impact T-scores were significantly lower in participants with low BMD and ON (38.3 [37.4, 40.1]), compared to those with either low BMD (49.5 [43.6, 54.4), p=3x10-5 or ON (52.7 [45.3, 57]), p=2x10-4 alone. Whether sickle cell-related low BMD results from impaired bone formation and/or accelerated bone loss remains unclear. Understanding how low bone density, with or without osteonecrosis, mediates SCD pain warrants further investigation. NCT05283148.},
}

@article {pmid41134118,
year = {2025},
author = {Chua, KJ and Quilang, RC and Sallinger, K and Aktipis, CA and Arck, P and Bianchi, DW and Chang, HD and Cleaves, HJ and Eikmans, M and Fjeldstad, HES and Haig, D and Harrington, WE and Horsnell, W and Jacobsen, DP and Kamper-Jørgensen, M and Kanaan, SB and Khosrotehrani, K and Lambert, NC and Nelson, JL and Olsen, MB and Pan, TD and Prins, JR and Schildberg, FA and Staff, AC and Ståhlberg, A and Stelzer, IA and Urbschat, C and Way, SS and Wilson, MA and Ye, J and Kroneis, T and Boddy, AM},
title = {Identifying Key Questions and Challenges in Microchimerism Biology.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e14969},
doi = {10.1002/advs.202514969},
pmid = {41134118},
issn = {2198-3844},
support = {62214//John Templeton Foundation/ ; //Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health/ ; },
abstract = {Microchimerism research has recently gained renewed attention despite known existence of these rare cells for decades. Fetal and maternal microchimeric-derived cells may have functional capabilities, and are increasingly associated with both beneficial and adverse health outcomes. Yet, establishing the role of microchimerism in health has been largely constrained methodologically and theoretically. The Microchimerism, Human Health, and Evolution Project address these challenges by calling on 29 leading microchimerism experts to put forth key research questions that can substantially advance the field. Seven major categories are identified: function and mechanism; microchimerism in interventions, treatment, and transplant; mapping "generational microchimerism"; evolution; microchimerism detection; appropriate experimental model systems; and definition of microchimerism. Identifying these questions - and continuing to find answers - will be crucial for advancing the knowledge of microchimerism in health and disease.},
}

@article {pmid41130408,
year = {2025},
author = {Le, X and Baik, C and Cho, BC and Riess, JW and Piotrowska, Z and Johannes de Langen, A and Goldberg, SB and Goldman, JW and Reguart, N and Shiraishi, Y and Ambrose, H and Fraenkel, PG and Ruiz, BM and Smith, PE and Tang, KH and Yu, HA},
title = {Osimertinib Plus Savolitinib in Patients With EGFR-Mutated Advanced NSCLC With MET Alterations After First-Line Osimertinib: Clinical Outcomes, Safety, and Biomarker Analysis: A Brief Report.},
journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtho.2025.10.009},
pmid = {41130408},
issn = {1556-1380},
abstract = {INTRODUCTION: The ORCHARD (NCT03944772) study was conducted to characterize resistance mechanisms and identify optimal treatments following progressive disease (PD) on first-line osimertinib. We report results from the osimertinib plus savolitinib module.

METHODS: Patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) with PD on first-line osimertinib with MET gene amplification (≥4 copies of MET over tumor ploidy) per next-generation sequencing of a post-progression biopsy received osimertinib plus savolitinib. Primary endpoint was investigator-assessed objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), duration of response (DoR) and overall survival (OS), and safety. Correlation of ORR with baseline molecular alterations was an exploratory analysis.

RESULTS: Thirty-two patients were enrolled; all had tumors with MET amplification. At primary analysis cutoff (January 2023), confirmed ORR was 47% (80% confidence interval [CI]: 35-60). Median DoR was 14.5 months (95% CI: 5.6-18.7). Median PFS was 7.6 months (95% CI: 3.2-15.9). There was a trend towards increased ORR in patients with high MET gene copy number (≥10 versus <10). Fourteen patients (44%) had grade ≥3 treatment-emergent adverse events; most commonly pneumonia (n = 3; 9%). At final database lock (May 2024), 20 patients (63%) had died; median OS was 20.7 months (95% CI: 9.9-34.8).

CONCLUSIONS: Osimertinib plus savolitinib demonstrated encouraging clinical benefit in patients with EGFR-mutated advanced NSCLC and MET amplification following PD on first-line osimertinib. Safety was consistent with profiles of the individual drugs.},
}

@article {pmid41129763,
year = {2025},
author = {Einstein, DJ and Abel, ML and Aragon-Ching, JB and Arlen, PM and Autio, KA and Bilusic, M and Carducci, MA and Choyke, PL and Citrin, DE and Figg, WD and Graff, JN and Gulley, JL and Halabi, S and Karzai, F and Lindenberg, L and Markowski, MC and Marshall, CH and McNeel, DG and Mena, E and Moon, H and Pachynski, RK and Paller, CJ and Patel, KR and Posadas, EM and Pienta, KJ and Regan, MM and Sena, LA and Walmsley, CS and Wei, XX and Yu, EY and Tran, PT and Madan, RA},
title = {National Cancer Institute's Working Group on Biochemically Recurrent Prostate Cancer: Clinical Trial Design Considerations.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2501693},
doi = {10.1200/JCO-25-01693},
pmid = {41129763},
issn = {1527-7755},
abstract = {PURPOSE: Biochemical recurrence (BCR) of prostate cancer (PCa) after definitive surgery and/or radiation (including salvage strategies) is a burgeoning area of clinical research inspired by ultrasensitive next-generation imaging. Most phase III trials in PCa have focused on metastatic disease, defined by conventional imaging. Despite the emergence of new imaging, clinical trial principles from metastatic studies will not optimize future BCR trials.

METHODS: A Working Group convened at the National Cancer Institute on November 13, 2024 (NCI BCR WG). Key areas of discussion included nomenclature, baseline criteria for data capture, imaging considerations, delineation of high-risk populations to be targeted for trial development, requirements of metastasis-directed therapy (MDT) or hormonal therapy, quality-of-life considerations, and potential study end points.

RESULTS: The NCI BCR WG defined the novel term "prostate-specific membrane antigen (PSMA)+BCR" to identify the emerging concept of recurrent PCa identifiable only on PSMA positron emission tomography (PET), overlapping with BCR and distinct from metastatic hormone-sensitive PCa as traditionally defined by conventional imaging. The WG suggested defining high-risk BCR with a prostate-specific antigen doubling time of ≤6 months, regardless of PET findings. The WG provided recommendations for baseline data capture and imaging requirements. Neither systemic therapy nor MDT were considered mandatory for control arms. The WG also discussed novel end points and quality-of-life metrics in this disease space.

CONCLUSION: These discussions should inform future clinical BCR trials in this distinct disease space relative to metastatic disease defined by conventional imaging. The NCI BCR WG strongly advocates that future trials explore deintensification of treatment to minimize toxicity in this relatively indolent disease state.},
}

@article {pmid41129758,
year = {2025},
author = {Bagshaw, P and Potter, JD and Griffiths, N and Hornblow, A and Cox, B and Gower, K},
title = {Nurse endoscopists: a rational response to rising rates of young-onset colorectal cancer in Aotearoa New Zealand.},
journal = {The New Zealand medical journal},
volume = {138},
number = {162},
pages = {76-86},
doi = {10.26635/6965.7100},
pmid = {41129758},
issn = {1175-8716},
mesh = {Humans ; New Zealand/epidemiology ; *Colorectal Neoplasms/epidemiology/diagnosis/nursing ; Middle Aged ; *Colonoscopy/nursing ; *Early Detection of Cancer ; Sigmoidoscopy/nursing ; Age of Onset ; Incidence ; *Mass Screening ; Aged ; Adult ; Female ; Male ; },
abstract = {Young-onset (<50 years) colorectal cancer (YOCRC) has been increasing in Aotearoa New Zealand since the birth cohort born around the mid-1950s. Possible responses include education and public health measures, none of which are likely to make a major impact in the foreseeable future. Many YOCRCs are presenting at late stages with predominantly distal cancers. Our current National Bowel Screening Programme (NBSP), screening people 60-75 years, was introduced with inadequate resources; as a result, some colonoscopy services have been moved from symptomatic cases to screening, resulting in diagnostic delays and poorer outcomes. Extending screening to 40 or 45 years will markedly increase the need for follow-up colonoscopies and stretch services beyond breaking point. Sigmoidoscopy is associated with a substantial and sustained reduction in risk of distal colorectal cancer incidence and mortality. As there are too few endoscopists for the existing workload, increasing the nurse endoscopist workforce is a rational step. Initial training would focus on flexible sigmoidoscopy (FS) and concentrate on symptomatic patients <50 years. Steadily increasing nurse endoscopist numbers will contribute to management of the rising incidence of YOCRC. Without disrupting the NBSP or putting much extra strain on need for follow-up colonoscopies, nurse-led FS clinical services can expand to anyone with relevant symptoms and, as a longer-term goal, eventually become part of an expanded screening programme that could include one-off FS at age 50. If we are agreed that this is essential, training and service must be adequately funded and accompanied by a public advocacy campaign to ensure sufficient resources.},
}

Humans
New Zealand/epidemiology
*Colorectal Neoplasms/epidemiology/diagnosis/nursing
Middle Aged
*Colonoscopy/nursing
*Early Detection of Cancer
Sigmoidoscopy/nursing
Age of Onset
Incidence
*Mass Screening
Aged
Adult
Female
Male

@article {pmid41129365,
year = {2025},
author = {Watling, CZ and Campbell, PT and Graubard, BI and Wang, Y and Gewirtz, AT and Zhang, X and Barnett, MJ and Buring, JE and Chen, Y and Eliassen, AH and Gaziano, JM and Hofmann, JN and Huang, WY and Kang, JH and Koshiol, J and Loftfield, E and Lee, IM and Moore, SC and Mucci, LA and Neuhouser, ML and Newton, CC and Purdue, MP and Sesso, HD and Shrubsole, M and Sinha, R and Tinker, L and Triplette, M and Um, CY and Visvanathan, K and Watts, EL and Wactawski-Wende, J and Willett, W and Wu, F and Zheng, W and Barupal, D and Petrick, JL and McGlynn, KA},
title = {Pre-diagnostic immunological markers of bacterial translocation and liver cancer risk: A nested case-control analysis of 12 prospective cohorts.},
journal = {International journal of cancer},
volume = {},
number = {},
pages = {},
doi = {10.1002/ijc.70201},
pmid = {41129365},
issn = {1097-0215},
support = {//American Cancer Society/ ; //National Institutes of Health Intramural/ ; 75N92021D00001/NH/NIH HHS/United States ; 75N92021D00002/NH/NIH HHS/United States ; 75N92021D00003/NH/NIH HHS/United States ; 75N92021D00004/NH/NIH HHS/United States ; 75N92021D00005/NH/NIH HHS/United States ; CA047988/NH/NIH HHS/United States ; CA182913/NH/NIH HHS/United States ; HL043851/NH/NIH HHS/United States ; HL080467/NH/NIH HHS/United States ; HL09935/NH/NIH HHS/United States ; CA34944/NH/NIH HHS/United States ; CA40360/NH/NIH HHS/United States ; CA097193/NH/NIH HHS/United States ; HL26490/NH/NIH HHS/United States ; HL34595/NH/NIH HHS/United States ; NCI U01 167552/NH/NIH HHS/United States ; U01CA202979/NH/NIH HHS/United States ; U01CA164974/NH/NIH HHS/United States ; U01CA63673/NH/NIH HHS/United States ; UM1CA167462/NH/NIH HHS/United States ; U01CA167462/NH/NIH HHS/United States ; U24ES035386/NH/NIH HHS/United States ; UM1CA186107/NH/NIH HHS/United States ; 187861/CAPMC/CIHR/Canada ; },
abstract = {The gut-liver axis may play an important role in hepatocarcinogenesis. However, limited prospective research has explored associations with liver cancer risk. We conducted a nested case-control study based in 12 prospective cohort studies from across the United States, which included 867 cases of liver cancer and 867 matched controls. We measured bacterial translocation markers, specifically immunoglobulin (Ig) A, IgG, and IgM against lipopolysaccharide and flagellin; soluble CD14 (a co-receptor for lipopolysaccharide); and lipopolysaccharide-binding protein. Multivariable conditional logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) between bacterial translocation marker concentrations per doubling in concentrations and liver cancer risk. Lipopolysaccharide-binding protein concentrations were most strongly associated with higher liver cancer risk (OR per doubling in concentrations: 1.48, 95% CI: 1.23-1.79). Concentrations of anti-flagellin IgA (1.13, 1.01-1.28) and IgG (1.13, 1.01-1.28), anti-lipopolysaccharide IgG (1.20, 1.01-1.42), and soluble CD14 (1.12, 1.01-1.24) were also associated with liver cancer risk. When analyses were separated into hepatocellular carcinoma (HCC, N = 436 cases) and intrahepatic cholangiocarcinoma (ICC, N = 110 cases), no evidence of heterogeneity was observed except for lipopolysaccharide-binding protein concentrations, which were positively associated with HCC (1.77, 1.34-2.33) but not ICC (0.67, 0.37-1.22; p-heterogeneity = .003). Associations did not differ by time to liver cancer diagnosis or other subgroups. These findings support the role of gut barrier dysfunction in hepatocarcinogenesis, necessitating further research to understand the complex interplay among the mechanisms and risk factors disrupting the gut barrier, microbiota, and liver cancer.},
}

@article {pmid41129142,
year = {2025},
author = {Jani, S and Bencomo, T and Shasha, C and Pulliam, T and Jojic, A and Church, CD and Gooley, TA and Koelle, DM and Newell, EW and Nghiem, P},
title = {Circulating neoantigen- and viral oncoprotein-specific CD8+ T cells share a transcriptional signature.},
journal = {Cancer immunology research},
volume = {},
number = {},
pages = {},
doi = {10.1158/2326-6066.CIR-25-0082},
pmid = {41129142},
issn = {2326-6074},
abstract = {Tumor-specific CD8+ T cells in blood appear to be important for and predictive of response to anti-PD-1 therapies. However, as most tumor antigens are unique to a given patient, identification of tumor-specific CD8+ T cells is not routinely feasible. Here, we characterized polyomavirus-specific CD8+ T cells from blood of 17 patients with virus-driven Merkel cell carcinoma (MCC). We identified a 98-gene signature, SPoTT (Signature of Peripheral Tumor-specific CD8+ T cells), that discriminated circulating tumor-specific CD8+ T cells from other T cells in immunotherapy-naïve patients. We observed profound transcriptomic differences among tumor-specific CD8+ T cells from blood versus from tumor. In validation cohorts of MCC, as well as neoantigen-driven cancers, SPoTT was able to identify viral oncoprotein- and neoantigen-specific CD8+ T cells with both sensitivity and specificity above 75%. We also tested a previously described 151-gene signature (NeoTCR_PBL) trained on neoantigen-specific CD8+ T cells and found it was able to recognize MCPyV-specific T cells with sensitivity of 66% and a specificity of 88%. These findings show that circulating tumor-specific CD8+ T cells share fundamental characteristics across diverse tumor antigen types. More broadly, insights into antitumor T cells gained from virus-driven cancers are also likely to be relevant in mutationally-driven cancers.},
}

@article {pmid41129124,
year = {2025},
author = {Su, CT and Ramsey, SD and Shankaran, V},
title = {Can We Use Credit Data to Assess Cancer Financial Hardship?.},
journal = {JAMA oncology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaoncol.2025.4371},
pmid = {41129124},
issn = {2374-2445},
}

@article {pmid41128595,
year = {2025},
author = {Albirair, M and Nyame, Y and Gulati, R and Etzioni, R},
title = {Age-Specific racial disparities in the incidence of fatal prostate cancer: an analytic deconstruction.},
journal = {JNCI cancer spectrum},
volume = {},
number = {},
pages = {},
doi = {10.1093/jncics/pkaf103},
pmid = {41128595},
issn = {2515-5091},
abstract = {BACKGROUND: Black men in the United States bear a disproportionate share of the prostate cancer (PCa) burden, with more than 50% higher incidence and double the mortality compared with White men. Previous studies have examined racial disparities in the incidence of fatal PCa (fPCa), defined as diagnosis leading to disease-specific death within 10 years and found that they are greater in younger versus older men. However, the extent to which these trends are driven by disparities in incidence or survival is unknown.

METHODS: We conduct a retrospective analysis of data from the Surveillance, Epidemiology, and End Results program over the period 1980-2009 to decompose the incidence of fPCa into incidence and 10-year probability of death and quantify the relative disparities in these metrics by age at diagnosis.

FINDINGS: We find that relative PCa incidence for Black versus White men significantly decreases by 0.116 units with each successive five-year age group (95% CI = -0.183 to -0.049) but the relative probability of death within 10 years does not differ significantly by age (slope = -0.012, 95% CI = -0.060 to 0.035). Further, this deconstruction is similar before and after the introduction of prostate-specific antigen screening.

CONCLUSION: We conclude that higher relative incidence of fPCa in young Black men vs young White men appears to be largely driven by their significantly increased incidence of disease. This finding supports investigating targeted screening of Black men beginning at younger ages than White men.},
}

@article {pmid41125870,
year = {2025},
author = {Sasaki, K and Bhatia, V and Asano, Y and Bakhtiari, J and Kaur, P and Wang, C and Matsuo, T and Dubois, O and Chiu, PC and Gun, D and Singh, C and Panagi, I and Noblecourt, L and Nikolaidi, M and Chong, T and Javier, G and Priceman, SJ and Chapuis, AG and Lee, JK and Ishihara, J},
title = {Collagen-binding IL-12-armoured STEAP1 CAR-T cells reduce toxicity and treat prostate cancer in mouse models.},
journal = {Nature biomedical engineering},
volume = {},
number = {},
pages = {},
pmid = {41125870},
issn = {2157-846X},
support = {W81XWH-21-1-0581//U.S. Department of Defense (United States Department of Defense)/ ; HT9425-23-1-0089//U.S. Department of Defense (United States Department of Defense)/ ; W81XWH-21-1-0581//U.S. Department of Defense (United States Department of Defense)/ ; SBF007\100097/AMS_/Academy of Medical Sciences/United Kingdom ; RIA21-ST2-010/PCUK_/Prostate Cancer UK/United Kingdom ; TLD-CAF24-006/PCUK_/Prostate Cancer UK/United Kingdom ; RIA21-ST2-010/PCUK_/Prostate Cancer UK/United Kingdom ; 202160429//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; ALTF 56-2022//European Molecular Biology Organization (EMBO)/ ; Prostate Cancer Foundation Young Investigator Awards//Prostate Cancer Foundation (PCF)/ ; },
abstract = {Immunosuppressive microenvironments, the lack of immune infiltration, and antigen heterogeneity pose challenges for chimaeric antigen receptor (CAR)-T cell therapies applied to solid tumours. Previously, CAR-T cells were armoured with immunostimulatory molecules, such as interleukin 12 (IL-12), to overcome this issue, but faced high toxicity. Here we show that collagen-binding domain-fused IL-12 (CBD-IL-12) secreted from CAR-T cells to target human six transmembrane epithelial antigen of prostate 1 (STEAP1) is retained within murine prostate tumours. This leads to high intratumoural interferon-γ levels, without hepatotoxicity and infiltration of T cells into non-target organs compared with unmodified IL-12. Both innate and adaptive immune compartments are activated and recognize diverse tumour antigens after CBD-IL-12-armoured CAR-T cell treatment. A combination of CBD-IL-12-armoured CAR-T cells and immune checkpoint inhibitors eradicated large tumours in an established prostate cancer mouse model. In addition, human CBD-IL-12-armoured CAR-T cells showed potent anti-tumour efficacy in a 22Rv1 xenograft while reducing circulating IL-12 levels compared with unmodified IL-12-armoured CAR-T cells. CBD fusion to potent payloads for CAR-T therapy may remove obstacles to their clinical translation towards elimination of solid tumours.},
}

@article {pmid41124669,
year = {2025},
author = {Berman, JN and Verma, A and Viola, SA and Alonzo, T and Wang, YC and Brodersen, LE and Loken, MR and Beckman, AK and Hirsch, BA and Raimondi, S and Chisholm, KM and Ma, X and Ries, RE and Meshinchi, S and Gamis, AS and Schore, RJ and Taub, JW and Kolb, EA and Cooper, TM and Hitzler, JK},
title = {Molecular Risk Markers Define Risk of Relapse in Myeloid Leukemia of Down syndrome Beyond Measurable Residual Disease.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025017837},
pmid = {41124669},
issn = {2473-9537},
abstract = {Myeloid leukemia of Down syndrome (ML-DS) is a distinct form of pediatric acute myeloid leukemia (AML) that responds to reduced intensity chemotherapy as compared to non-DS AML that requires intensive chemotherapy and often stem cell transplant. While most patients with ML-DS have a favorable prognosis, outcomes for those with refractory or relapsed disease are dismal. Children's Oncology Group (COG) study AAML1531 introduced the use of minimal residual disease measured by multi-parameter flow cytometry at the end of the first course of induction therapy (EOI-1 MRD) for risk stratification of treatment intensity. Of 280 ML-DS patients enrolled, 41 were classified as high risk (HR) due to positive EOI-1 MRD and treated with intensified chemotherapy similar to that used for pediatric non-DS AML. Treatment intensification did not improve the 2-year event-free survival compared to MRD-positive patients treated with reduced intensity therapy in predecessor study AAML0431(80.5 + 12.4% vs. 76%, p=0.247) or overall survival (80.5 + 12.4% vs. 76.2 + 18.6%, p=0.819), but significantly increased the frequency of febrile neutropenia and sepsis events. While stratification of treatment intensity based on MRD was not beneficial, molecular markers of relapse risk proposed by the Japan Children's Cancer Group for ML-DS (alterations of CDKN2A, ZBTB7A, JAK2, TP53) proved prognostic. Relapse risk was 50% in AAML1531 HR patients with any high risk molecular marker compared to 6.7% in those without. Similar relapse results were obtained in the MRD-negative AAML1531 group, suggesting molecular risk markers can predict outcome and thus be used to stratify therapy in ML-DS. https://clinicaltrials.gov/study/NCT02521493.},
}

@article {pmid41124233,
year = {2025},
author = {Cortés, J and Punie, K and Barrios, C and Hurvitz, SA and Schneeweiss, A and Sohn, J and Tokunaga, E and Brufsky, A and Park, YH and Xu, B and Hegg, R and Oliveira, M and Fabi, A and Vaksman, N and Valdez, T and Zhang, X and Lai, C and Tolaney, SM and , },
title = {Sacituzumab Govitecan in Untreated, Advanced Triple-Negative Breast Cancer.},
journal = {The New England journal of medicine},
volume = {},
number = {},
pages = {},
doi = {10.1056/NEJMoa2511734},
pmid = {41124233},
issn = {1533-4406},
abstract = {BACKGROUND: Patients with previously untreated, locally advanced, unresectable or metastatic triple-negative breast cancer who are not candidates for inhibitors of programmed cell death protein 1 (PD-1) or programmed death ligand 1 (PD-L1) have limited treatment options.

METHODS: In this international, phase 3, open-label, randomized trial, we enrolled patients with previously untreated, advanced triple-negative breast cancer who were not candidates for PD-1 or PD-L1 inhibitors owing to previous use or coexisting conditions. Patients had either PD-L1-negative tumors with a combined positive score (CPS; the number of PD-L1-staining tumor cells, lymphocytes, and macrophages divided by the total number of viable tumor cells, multiplied by 100) of less than 10 or PD-L1-positive tumors with a CPS of 10 or higher and were assigned in a 1:1 ratio to receive sacituzumab govitecan or chemotherapy (paclitaxel, nanoparticle albumin-bound paclitaxel, or gemcitabine plus carboplatin). The primary end point was progression-free survival, assessed by blinded independent central review. Secondary end points included overall survival, objective response, the duration of response, and safety.

RESULTS: Among 558 patients, median progression-free survival was 9.7 months (95% confidence interval [CI], 8.1 to 11.1) with sacituzumab govitecan and 6.9 months (95% CI, 5.6 to 8.2) with chemotherapy (stratified hazard ratio for disease progression or death, 0.62; 95% CI, 0.50 to 0.77; P<0.001). An objective response was confirmed in 48% of patients (95% CI, 42 to 54) who received sacituzumab govitecan and 46% (95% CI, 40 to 52) who received chemotherapy; the median response duration was 12.2 months (95% CI, 9.7 to 13.8) and 7.2 months (95% CI, 5.7 to 8.4), respectively. Adverse events of grade 3 or higher occurred in 66% of patients who received sacituzumab govitecan (most frequently neutropenia [in 43%], diarrhea [in 9%], and leukopenia [in 7%]) and in 62% of patients who received chemotherapy (most frequently neutropenia [in 41%], anemia [in 16%], and leukopenia [in 13%]). The incidence of adverse events that led to discontinuation of sacituzumab govitecan or at least one chemotherapy drug was 4% and 12%, respectively.

CONCLUSIONS: Sacituzumab govitecan led to significantly longer progression-free survival than chemotherapy among patients with advanced triple-negative breast cancer who were not candidates for treatment with PD-1 or PD-L1 inhibitors. The incidence of adverse events of grade 3 or higher with sacituzumab govitecan was similar to that with chemotherapy, but adverse events were common. (Funded by Gilead Sciences; ASCENT-03 ClinicalTrials.gov number, NCT05382299.).},
}

@article {pmid41124032,
year = {2025},
author = {Panian, J and Henderson, NC and Herchenhorn, D and Barata, PC and Bilen, MA and Graham, L and Heath, E and Hwang, C and Supernois, A and Kilari, D and Thapa, B and Koshkin, VS and Jindal, T and Nauseef, JT and Sokolova, A and Amery, T and Zakharia, Y and Schweizer, MT and Raychaudhuri, R and Reichert, ZR and Dorff, T and Armstrong, AJ and Wang, J and Alva, A and McKay, RR},
title = {Genomic Alterations and Associated Outcomes in Patients with PSMA-Positive Metastatic Castration-Resistant Prostate Cancer treated with 177Lu-PSMA-617.},
journal = {The oncologist},
volume = {},
number = {},
pages = {},
doi = {10.1093/oncolo/oyaf358},
pmid = {41124032},
issn = {1549-490X},
abstract = {BACKGROUND: 177Lu-PSMA-617 is approved for patients with metastatic castration-resistant prostate cancer (mCRPC). Although treatment is associated with improved outcomes, not all patients benefit and response is heterogeneous. We aim to characterize genomic alterations associated with benefit to 177Lu-PSMA-617.

METHODS: This study used the Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort (PROMISE) clinical-genomic database (n = 2445). The primary endpoint was ≥50% PSA decline (PSA50) from baseline with 177Lu-PSMA-617 in molecular subgroups. Secondary endpoints included 90% PSA decline (PSA90). Associations were assessed using Fisher's exact test and Cox regression in multivariable analysis.

RESULTS: We identified 183 mCRPC patients treated with 177Lu-PSMA-617. Median number of prior lines of mCRPC therapy was three. Overall, PSA50 was 49%, median progression-free survival was 7.6 months, and median overall survival was 13.9 months. NF1 (n = 8) and FOXA1 alterations (n = 5) were associated with increased PSA50 (88% vs. 47%, p = 0.03 for NF1; 100% vs. 47%, p = 0.03 for FOXA1). Among CRPC sequenced tumors (n = 119), androgen receptor (AR) alterations (n = 58) were associated with lower PSA50 (38% vs. 60%, p = 0.03). While any tumor suppressor genes (TSG) (PTEN, TP53, RB1) (n = 109) or TP53 (n = 83) alteration were associated with lower PSA90 (p = 0.02 for both), NF1 (n = 8) and FOXA1 alterations were associated with higher PSA90 (p = 0.03 and p = 0.003, respectively).

CONCLUSIONS: This analysis identifies potential genomic predictors of response to 177Lu-PSMA-617, with NF1 and FOXA1 alterations associated with favorable outcomes and AR and TSG alterations with diminished response. These hypothesis-generating findings suggest genomic profiling may inform selection for PSMA-targeted therapy and warrant prospective validation in larger cohorts.

IMPLICATIONS OF PRACTICE: In this study, we evaluate the use of genetic markers to predict response to treatment with 177Lu-PSMA-617 in patients with metastatic prostate cancer. We identified that alterations in the androgen receptor (AR) and tumor suppressor genes (TSG) were associated with a worse response to 177Lu-PSMA-617, which FOXA1 and NF1 alterations were associated with improved outcomes. These data are hypothesis generating and warrant validation in larger studies. Identifying predictive markers to 177Lu-PSMA-617 can better optimize treatment selection for this therapy.},
}

@article {pmid41120126,
year = {2025},
author = {Patel, SP and Othus, M and Chae, YK and Azenkot, T and Wagner, MJ and Threlkel, S and Farley, JH and Magner, CM and Chen, HX and Sharon, E and Ryan, CW and Blanke, C and Kurzrock, R},
title = {Multicenter phase II trial of ipilimumab and nivolumab in metastatic or unresectable perivascular epithelioid cell tumor (PEComa): a substudy of Dual Anti-CTLA-4 and Anti-PD-1 blockade in Rare Tumors (DART) SWOG S1609 (Cohort 38).},
journal = {Journal for immunotherapy of cancer},
volume = {13},
number = {10},
pages = {},
pmid = {41120126},
issn = {2051-1426},
mesh = {Humans ; Female ; *Nivolumab/pharmacology/therapeutic use ; Middle Aged ; Male ; *Ipilimumab/pharmacology/therapeutic use ; Adult ; Aged ; *Perivascular Epithelioid Cell Neoplasms/drug therapy/pathology/mortality ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/pharmacology/adverse effects ; Young Adult ; *CTLA-4 Antigen/antagonists & inhibitors ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; *Programmed Cell Death 1 Receptor/antagonists & inhibitors ; },
abstract = {BACKGROUND: Malignant perivascular epithelioid cell tumors (PEComas) are ultra-rare, aggressive mesenchymal neoplasms associated with poor outcomes. Standard-of-care systemic therapy includes mammalian target of rapamycin (mTOR) inhibition and chemotherapy. Immune checkpoint inhibition has not been previously studied in patients with advanced PEComas in a prospective clinical trial.

METHODS: This is an open-label phase 2 trial of ipilimumab (1 mg/kg intravenously every 6 weeks) plus nivolumab (240 mg intravenously every 2 weeks) in rare tumors; here we report the cohort of patients with advanced malignant PEComa recruited from >1,000 sites across the USA. Primary end point was objective response rate, with progression-free survival, overall survival, and toxicity as secondary end points.

RESULTS: 17 patients were enrolled (N=16 evaluable). Median age was 59.5 years (range, 22-77 years) and the majority were female (81%). Best responses included partial response (18.8%), stable disease for <6 months (25.0%), and progressive disease (56.3%). Median OS was 7.5 months (95% CI 3.4 to 34.6) and median PFS was 1.9 months (95% CI 1.8 to 11.8). PFS in responding patients was 11.8, 18.9, and 34.6 months. Available genomic sequencing showed TSC, ATRX, and TP53 mutations; no TFE3 fusions were identified (N=7). Nearly all patients experienced a treatment-related adverse event (AE) of any grade, while 37.5% experienced a grade 3-4 AE. Most common AEs were fatigue (43.8%), pruritus (37.5%), rash (25.0%), and aspartate aminotransferase increase (25.0%). There were no grade 5 AEs.

CONCLUSIONS: The combination of ipilimumab and nivolumab demonstrated responses in 18.8% of patients with advanced malignant PEComas. Dual immunotherapy may be an alternative treatment option for certain patients, including those who are unable to tolerate or do not desire prolonged treatment with chemotherapy or mTOR inhibition or have failed to respond to other therapies. Ipilimumab and nivolumab warrants further investigation in this and other rare soft tissue sarcomas.},
}

Humans
Female
*Nivolumab/pharmacology/therapeutic use
Middle Aged
Male
*Ipilimumab/pharmacology/therapeutic use
Adult
Aged
*Perivascular Epithelioid Cell Neoplasms/drug therapy/pathology/mortality
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use/pharmacology/adverse effects
Young Adult
*CTLA-4 Antigen/antagonists & inhibitors
*Immune Checkpoint Inhibitors/therapeutic use/pharmacology
*Programmed Cell Death 1 Receptor/antagonists & inhibitors

@article {pmid41118367,
year = {2025},
author = {Carter, JJ and Hurlburt, NK and Scherer, EM and Singh, S and Rodarte, JV and Smith, RA and Lewis, P and Kinzelman, R and Kieltyka, J and Cabãn, ME and Wipf, GC and Pancera, M and Galloway, DA},
title = {Human monoclonal antibodies to HPV16 show evidence for common developmental pathways and public epitopes.},
journal = {PLoS pathogens},
volume = {21},
number = {10},
pages = {e1013086},
doi = {10.1371/journal.ppat.1013086},
pmid = {41118367},
issn = {1553-7374},
mesh = {*Antibodies, Monoclonal/immunology ; Humans ; *Human papillomavirus 16/immunology ; *Antibodies, Viral/immunology ; *Epitopes/immunology ; Capsid Proteins/immunology ; Antibodies, Neutralizing/immunology ; *Papillomavirus Infections/immunology/prevention & control ; Papillomavirus Vaccines/immunology ; Oncogene Proteins, Viral/immunology ; },
abstract = {Antibodies to human papillomavirus (HPV) primarily recognize surface exposed residues on five loops of the major capsid protein (L1) that vary significantly among HPV types. We determined which loops were required for neutralization for 68 HPV16 specific human monoclonal antibodies (mAbs) cloned from participants who received an HPV vaccine and describe molecular features of those antibodies. Chimeric HPV16 pseudovirus (cpsV), each having one surface loop bearing multiple amino acid substitutions, were used to determine neutralization specificity. The HPV16-FG-loop was the loop most frequently required for neutralization (42 of 68, 61.8%), however, all surface loops were required for neutralization by multiple mAbs: HI (13, 19.1%), DE (15, 22.1%), EF (five, 7.4%), BC (four, 5.9%). Antibodies that required multiple loops were common (17, 25.0%). Three mAbs (4.4%) required sequences on the c-terminus of L1 and for another three mAbs the neutralization specificity could not be determined. Two types of mAbs appeared to be overrepresented: ten mAbs used immunoglobin heavy chain variable region 2-70 (IGHV2-70) with immunoglobin light chain variable region 1-40 (IGLV1-40), having characteristic mutations in complementarity determining region two (CDRL2) of the light chain. Cryogenic electron microscopy (Cryo-EM) revealed that two of these antibodies bound five Fabs per capsomer interacting with all five L1-surface loops. The other type of mAbs that appeared to be overrepresented were nine mAbs using IGHV4-34, six of which also used DH3-16*02 with conserved CDRH3 sequences. Cryo-EM for one of these mAbs, that required the FG-loop for neutralization, was shown to bind one Fab per capsomer at the apex, interacting with the DE- and FG-loops, with sequences of the Fab CDRH3 inserted between the DE- and FG-loops from two L1 proteins. These two types of mAbs were found in the four participants suggesting that these antibodies shared developmental pathways and bound to similar immunodominant epitopes on the virus.},
}

*Antibodies, Monoclonal/immunology
Humans
*Human papillomavirus 16/immunology
*Antibodies, Viral/immunology
*Epitopes/immunology
Capsid Proteins/immunology
Antibodies, Neutralizing/immunology
*Papillomavirus Infections/immunology/prevention & control
Papillomavirus Vaccines/immunology
Oncogene Proteins, Viral/immunology

@article {pmid41117775,
year = {2025},
author = {Lai, Y and Song, D and Xia, L and Li, JJ},
title = {PseudotimeDE-fast: fast testing of differential gene expression along cell pseudotime.},
journal = {Bioinformatics (Oxford, England)},
volume = {},
number = {},
pages = {},
doi = {10.1093/bioinformatics/btaf573},
pmid = {41117775},
issn = {1367-4811},
abstract = {SUMMARY: Identifying differentially expressed (DE) genes along cell pseudotime is crucial for understanding dynamic biological processes captured by single-cell RNA sequencing. However, existing DE methods either produce invalid p-values by ignoring the uncertainty in pseudotime inference or struggle to scale with the growing size of modern datasets. To address these limitations, we introduce PseudotimeDE-fast, a scalable method for detecting DE genes along pseudotime with well-calibrated p-values. Through comprehensive simulations and real-data analyses, we demonstrate that PseudotimeDE-fast delivers comparable or superior performance to existing approaches while offering substantial improvements in computational efficiency.

AVAILABILITY: PseudotimeDE-fast is implemented in R with Rcpp acceleration and released under the MIT license. The source code is available at: https://github.com/dsong-lab/PseudotimeDE.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.},
}

@article {pmid41117635,
year = {2025},
author = {Davis, JW and Aragaki, AK and Harrington, LB and Rossouw, JE and Wells, G and Shadyab, A and Schnatz, PF and Shufelt, CL and Warsinger-Martin, L and Wild, RA and Manson, JE},
title = {Baseline use of aspirin or statins with oral estrogen and progestogens to prevent incident arterial or venous thrombotic events: a secondary analysis of the Women's Health Initiative trial.},
journal = {Menopause (New York, N.Y.)},
volume = {},
number = {},
pages = {},
pmid = {41117635},
issn = {1530-0374},
abstract = {OBJECTIVE: To evaluate whether effects of oral hormone therapy (HT) on risks of venous and arterial vascular events differ by baseline statin or aspirin use.

METHODS: We performed time-to-event analysis using data from the Women's Health Initiative menopausal HT randomized trials to assess risk of thrombotic events. Women were randomized to oral conjugated equine estrogens (CEEs) alone or placebo among women with prior hysterectomy (n = 10,739), and CEE with medroxyprogesterone acetate (MPA) or placebo among women with an intact uterus (n = 16,608), stratified by baseline personal use of statins and aspirin. We evaluated risk of prespecified, adjudicated thrombotic events, including coronary heart disease, stroke, venous thromboembolism, and/or composite major adverse cardiovascular events, at 2 and 5 years.

RESULTS: Baseline statin use (n = 827 in CEE-alone trial; n = 1,115 in CEE+MPA trial) or aspirin use (n = 2,212; n = 3,431) was limited. At 5-year follow-up, coronary heart disease risk for CEE-alone versus placebo was hazard ratio (HR) = 0.81 (95% CI: 0.44-1.49) in statin users, similar to nonusers, HR = 1.07 (95% CI: 0.82-1.40). For CEE+MPA, there was also no difference by statin use, HR = 1.02 (95% CI: 0.55-1.89) and HR = 1.47 (95% CI: 1.13-1.90), respectively. Neither statin nor aspirin exposure significantly modified effects of HT on any arterial or venous thrombotic outcome at 2 or 5 years.

CONCLUSIONS: In this secondary randomized clinical trial analysis, neither statins nor aspirin significantly modified effects of oral HT on key arterial or venous thrombotic outcomes at 2 or 5 years. Results, however, may be underpowered given low baseline exposure prevalence for both statins and aspirin.},
}

@article {pmid41117594,
year = {2025},
author = {Bacsik, DJ and Mills, MG and Monroe, LD and Spring, C and Perez-Osorio, AC and Reed, JC and Fang, FC and Bourassa, L and Roychoudhury, P and Crawford, KHD and Snekvik, K and Greninger, AL},
title = {Validation of H5 influenza virus subtyping RT-qPCR assay and low prevalence of H5 detection in 2024-2025 influenza virus season.},
journal = {Journal of clinical microbiology},
volume = {},
number = {},
pages = {e0041525},
doi = {10.1128/jcm.00415-25},
pmid = {41117594},
issn = {1098-660X},
abstract = {A sustained outbreak of H5N1 influenza virus among wild fowl and domestic livestock has caused more than 70 zoonotic infections in humans in North America, including two deaths. The United States Centers for Disease Control and Prevention has recommended rapid H5 subtyping for all hospitalized cases with influenza A virus infection to enable prompt initiation of antiviral treatment, as well as infection prevention and implementation of public health measures to control spread. To address these needs, we developed a qualitative multiplex RT-qPCR assay to subtype H5 influenza virus in nasal, nasopharyngeal, and conjunctival specimens with a limit of detection of 250 copies/mL. No cross-reactivity was observed with other common respiratory viruses, including seasonal H3N2 and H1N1 influenza A viruses. We retrospectively subtyped 590 influenza A virus-positive clinical specimens with Ct values less than 31 processed by University of Washington labs between March 2024 and February 2025, including 512 specimens collected during the 2024-2025 influenza season, and detected no H5 positives. After clinical implementation, we performed 150 clinically ordered H5 subtyping tests between February and April 2025 and again detected no positives. This work enhances clinical pandemic preparedness activities and highlights the exceedingly low prevalence of H5N1 influenza virus during the 2024-2025 respiratory season.IMPORTANCEThe spread of H5N1 influenza virus in the United States has led to the culling of almost 200 million birds, infected cow herds across 17 states, and resulted in 70 human infections as of July 2025. Rapid PCR subtyping of H5 influenza virus is critical to inform hospital infection prevention and public health to enable containment of viral transmission. Here, we report the design, validation, and clinical implementation of a qualitative multiplex H5-subtyping RT-qPCR assay for nasopharyngeal, nasal, and conjunctival swab specimens. Additionally, we offer the largest reported study of H5 subtyping of influenza A virus-positive specimens in the United States to date. No H5 infections were detected in 740 samples collected between March 2024 and April 2025 from patients with confirmed influenza A virus infection in a large academic medical system in Seattle, WA.},
}

@article {pmid41117001,
year = {2025},
author = {Gunn, CM and Boyer, N and Sheikh, S and Lee, JM and Woloshin, S and Specht, JM and Hubbard, RA and Bowles, EJA and Su, YR and Tosteson, ANA},
title = {Patient and Physician Perspectives on Using Risk Prediction to Support Breast Cancer Surveillance Decision Making.},
journal = {Medical decision making : an international journal of the Society for Medical Decision Making},
volume = {},
number = {},
pages = {272989X251379888},
doi = {10.1177/0272989X251379888},
pmid = {41117001},
issn = {1552-681X},
abstract = {IntroductionBreast cancer survivors have a higher risk of interval cancers relative to the screening population. Patient characteristics including features of the primary cancer and its treatment can help predict interval second breast cancer risk, but patient and physician perspectives on how risk prediction tools might enhance surveillance decision making are not well characterized.DesignWe conducted a qualitative study of women with breast cancer who had completed primary treatment and multispecialty physicians recruited through Breast Cancer Surveillance Consortium registries. We conducted semi-structured focus groups with 5 to 7 breast cancer survivors and individual physician interviews. All participants were presented with information about an interval cancer risk prediction tool. We elicited participant perspectives on aspects of the tool's design, relevance, and use for surveillance decision making. Data coding, thematic analysis, and interpretation were guided by the principles of theoretical thematic analysis.ResultsForty physician interviews and 4 focus groups involving 23 breast cancer survivors were analyzed. Two prominent areas of focus emerged: 1) perspectives on how a risk prediction tool would enhance and add value to patient-centered care and 2) risk prediction tools can be a means to improve communication about risk of in-breast recurrence or new breast cancer.ConclusionsThis study provides data on breast cancer survivor and physician perceptions of a new risk prediction tool to support surveillance imaging decisions among breast cancer survivors.ImplicationsAn interval second breast cancer risk prediction tool may promote evidence-based care across an array of physicians and different clinical settings. Future research should identify care delivery settings and features that promote adoption and support use in ways that improve shared decision making and patient outcomes.HighlightsThis qualitative study of breast cancer survivors and physicians found that risk prediction tools to support surveillance decisions were perceived positively when positioned as a supplement to the patient-physician relationship.Both patients and physicians said that a tool supported by strong evidence and accessible outputs would be valuable for shared decision making.},
}

@article {pmid41116172,
year = {2025},
author = {Hemberg, M and Marini, F and Ghazanfar, S and Al Ajami, A and Abassi, N and Anchang, B and Benayoun, BA and Cao, Y and Chen, K and Cuesta-Astroz, Y and DeBruine, Z and Dendrou, CA and De Vlaminck, I and Imkeller, K and Korsunsky, I and Lederer, AR and Li, JJ and Meysman, P and Miller, CL and Mullan, KA and Ohler, U and Panwar, P and Patikas, N and Schuck, J and Siu, JHY and Triche, TJ and Tsankov, A and van der Laan, SW and Yajima, M and Yang, J and Zanini, F and Jelic, I},
title = {Insights, opportunities, and challenges provided by large cell atlases.},
journal = {Genome biology},
volume = {26},
number = {1},
pages = {358},
pmid = {41116172},
issn = {1474-760X},
mesh = {*Single-Cell Analysis/methods ; Humans ; Animals ; *Computational Biology/methods ; *Atlases as Topic ; Databases, Genetic ; },
abstract = {The field of single-cell biology is growing rapidly, generating large amounts of data from a variety of species, disease conditions, tissues, and organs. Coordinated efforts such as CZI CELLxGENE, HuBMAP, Broad Institute Single Cell Portal, and DISCO allow researchers to access large volumes of curated datasets, including more than just scRNA-seq data. These resources have created an opportunity to build and expand the computational biology ecosystem to develop tools necessary for data reuse and for extracting novel biological insights. We highlight achievements made so far, areas where further development is needed, and specific challenges that need to be overcome.},
}

*Single-Cell Analysis/methods
Humans
Animals
*Computational Biology/methods
*Atlases as Topic
Databases, Genetic

@article {pmid41116168,
year = {2025},
author = {Gramatges, MM and Sanclemente, LN and Hall, L and Taylor, OA and Nuño, MM and Bhatia, S and Chow, EJ and Getz, KD and Hitzler, JK and Li, AM and McCloskey, K and Nathan, PC and O'Brien, MM and Patel, S and Verma, A and Yarbrough, AR and Richard, MA and Rosser, TC and Jacola, LM and Lupo, PJ and Rabin, KR},
title = {A multicenter observational cohort study in survivors of Down Syndrome-associated acute leukemia (ALTE22C1): a report from the Children's Oncology Group.},
journal = {BMC cancer},
volume = {25},
number = {1},
pages = {1611},
pmid = {41116168},
issn = {1471-2407},
support = {R01CA263000/CA/NCI NIH HHS/United States ; R03HD108261//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; },
abstract = {BACKGROUND: Down syndrome (DS) is a common genetic disorder resulting from an extra copy of genetic material from all or part of chromosome 21. Individuals with DS have a higher burden of co-occurring structural birth defects, neurocognitive delay, and chronic health conditions when compared to those without DS, as well as a 10 to 20-fold excess risk for acute leukemia (AL). Few studies have reported the late effects of cancer treatment in DS-AL survivors, and even fewer have compared outcomes to children with DS and no cancer history. The Children’s Oncology Group study ALTE22C1 was developed to address this knowledge gap.

METHODS: This study leverages both registry and site-based DS-AL survivor recruitment and a prospective/retrospective cohort design to compare chronic health conditions and neurocognitive outcomes experienced by DS-AL survivors to age and sex-matched individuals enrolled to a DS cohort for which cancer is exclusionary. Survivors 6–39 years old, ≥ 3 years from end of AL treatment, and in remission are eligible. Participants complete a medical conditions survey and neuropsychological battery by parent proxy and may also participate in an in-person physical and neurocognitive assessment. Biological samples are collected to evaluate molecular features associated with outcomes.

DISCUSSION: This cooperative group study will identify the prevalence and severity of medical and neurocognitive outcomes in DS-AL survivors compared with non-DS AL and DS controls without cancer history. Results are anticipated to inform clinical practice guidelines for DS-AL survivors and improve survivor outcomes through mitigation of outcome disparities in this vulnerable population.

TRIAL REGISTRATION: Children’s Oncology Group study ALTE22C1 is registered under the ClinicalTrials.gov identifier NCT05702645.},
}

@article {pmid41109336,
year = {2025},
author = {Batista, MV and Chaer, FE and Englund, JA and Boeckh, M and Carpenter, PA and Dadwal, SS and Waghmare, A and Navarro, D and Hirsch, HH and Piñana, JL and Papanicolaou, GA and Chemaly, RF},
title = {Corrigendum to 'American Society for Transplantation and Cellular Therapy Series #10: Management of Parainfluenza and Human Metapneumovirus Infections in Hematopoietic Cell Transplantation and Cellular Therapy Recipients' [Transplantation and Cellular Therapy 31 (2025) 624-638/ https://doi.org/10.1016/j.jtct.2025.06.016].},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.09.027},
pmid = {41109336},
issn = {2666-6367},
}

@article {pmid41108951,
year = {2025},
author = {Park, VY and Hippe, DS and Kazerouni, AS and Biswas, D and Bryant, ML and Li, I and Javid, SH and Kilgore, M and Kim, J and Kim, AG and Scheel, JR and Lowry, KP and Lam, DL and Partridge, S and Rahbar, H},
title = {Multiparametric breast MRI to problem-solve mammographically detected suspicious calcifications.},
journal = {European journal of radiology},
volume = {194},
number = {},
pages = {112467},
doi = {10.1016/j.ejrad.2025.112467},
pmid = {41108951},
issn = {1872-7727},
abstract = {OBJECTIVE: To evaluate the performance of multiparametric breast MRI to problem-solve mammographically-detected suspicious calcifications.

MATERIALS AND METHODS: Participants with mammographically-detected suspicious calcifications were prospectively enrolled between August 2017 to May 2023. Pre-biopsy multiparametric MRI (standard and high-temporal resolution dynamic contrast enhanced [DCE]-MRI acquisitions and diffusion-weighted imaging [DWI]) was performed. The associations of MRI features with outcomes - (1) any malignancy and (2) invasive or high-grade ductal carcinoma in situ [DCIS] only - were analyzed using univariable logistic regression. Multivariable models, sequentially incorporating clinical/mammographic, qualitative, and quantitative features, were developed using penalized logistic regression with the least absolute shrinkage and selection operator. Area under the receiver operating characteristic curves (AUC) were estimated via cross-validation and compared between models using bootstrap methods.

RESULTS: 81 women (mean age, 55 years ± 10 [standard deviation]) with 86 calcifications were included; 29 % (25/86) were malignant. Malignancy rates for non-enhancing mammographic Breast Imaging Reporting and Data System (BI-RADS) category 4a and 4b calcifications were 3.8 % (1/26) and 8.7 % (2/23), respectively, with no invasive cancer or high-grade DCIS. Mammographic BI-RADS category, MRI BI-RADS category, visibility on DWI, peak percent enhancement, functional tumor volume, and K[trans] values were associated with both outcomes (all p < 0.05). Multivariable models, including qualitative DCE-MRI assessments, showed higher AUCs (malignancy: 0.71-0.76; invasive cancer or high-grade DCIS: 0.78-0.91) than when including only clinical and mammographic features (malignancy: 0.57; invasive cancer or high-grade DCIS: 0.61, all p < 0.05). Further incorporation of DWI or quantitative MRI features did not improve AUCs (all ΔAUC ≤ 0).

CONCLUSION: Breast DCE-MRI aids in evaluating mammographic BI-RADS category 4a/4b calcifications without biopsy. DWI or quantitative MRI features may not further improve diagnostic performance.},
}

@article {pmid41108673,
year = {2025},
author = {Gogebakan, KC and Elsisi, Z and Montano-Campos, F and Owens, L and Zhao, Y and Gulati, R and Ferdinandus, J and Fendler, WP and Calais, J and Hope, TA and Carlsson, S and Fainberg, J and Laudone, V and Kunst, N and Berlin, A and Schipper, M and Barbour, A and Iravani, A and Etzioni, R},
title = {Prostate-specific membrane antigen positron emission tomography/computed tomography imaging as a precision diagnostic at prostate cancer recurrence after radical prostatectomy: Modeling long-term survival.},
journal = {Cancer},
volume = {131},
number = {21},
pages = {e70131},
doi = {10.1002/cncr.70131},
pmid = {41108673},
issn = {1097-0142},
support = {R35 CA274442/CA/NCI NIH HHS/United States ; CA097186/CA/NCI NIH HHS/United States ; CA253915/CA/NCI NIH HHS/United States ; R50:CA 221836/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Male ; *Prostatic Neoplasms/diagnostic imaging/mortality/surgery/pathology/therapy ; Prostatectomy ; *Positron Emission Tomography Computed Tomography/methods ; *Neoplasm Recurrence, Local/diagnostic imaging/mortality ; *Glutamate Carboxypeptidase II/metabolism ; *Antigens, Surface/metabolism ; Salvage Therapy ; Aged ; Middle Aged ; },
abstract = {BACKGROUND: Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT) is affecting the management of patients with prostate cancer with biochemical recurrence after radical prostatectomy. The long-term outcomes of tailoring salvage treatment on the basis of PSMA-PET/CT status remain to be determined.

METHODS: A decision-analytic model was developed to project incremental life-years of strategies that allocate treatments at biochemical recurrence after radical prostatectomy on the basis of PSMA-PET/CT status (PSMA-metastatic vs. PSMA-nonmetastatic). Modeled treatments are local/regional (radiation) or systemic (hormone therapy and doublet therapy), administered immediately or delayed. PSMA-metastatic status was assumed to lead to treatment intensification, whereas PSMA-nonmetastatic status would lead to deintensification. To project survival, data on progression to metastasis from a clinical cohort were combined with registry data on postmetastasis survival. Because of the lack of data on long-term treatment benefits by PSMA status, survival was projected by varying the hazard ratio (HR) for disease-specific death among PSMA-metastatic versus PSMA-nonmetastatic patients under delayed or local/regional regimens (HR1) and under immediate systemic regimens (HR2).

RESULTS: Mean life-years are projected to be 15.5 under the non-PSMA-tailored strategy, and mean incremental life-years range from 0.38 to 0.81 depending on HR1 and HR2. A greater benefit is projected when PSMA-metastatic status is more adverse under salvage regimens that do not include systemic agents.

CONCLUSIONS: This decision-analytic modeling study projects that PSMA-PET/CT-guided management at biochemical recurrence after radical prostatectomy yields a modest survival benefit under the specified model inputs and assumptions regarding treatment distributions. These findings may complement emerging data on the corresponding economic costs and health-related quality of life.},
}

Humans
Male
*Prostatic Neoplasms/diagnostic imaging/mortality/surgery/pathology/therapy
Prostatectomy
*Positron Emission Tomography Computed Tomography/methods
*Neoplasm Recurrence, Local/diagnostic imaging/mortality
*Glutamate Carboxypeptidase II/metabolism
*Antigens, Surface/metabolism
Salvage Therapy
Aged
Middle Aged

@article {pmid41108088,
year = {2025},
author = {Hurvitz, S and Simonelli, M and Yarza, R and Berz, D and Kitano, S and Del Conte, G and Acosta Eyzaguirre, D and Doger de Speville Uribe, BG and Maier, D and Erzen, D and Aykut Yazgili, S and Curigliano, G and Deng, T and Yan, M and Zhang, Q and Wang, X and Nakayama, I and Shitara, K},
title = {Beamion BCGC-1: phase Ib/II trial of zongertinib for advanced HER2-positive breast or gastroesophageal cancers.},
journal = {Future oncology (London, England)},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/14796694.2025.2569553},
pmid = {41108088},
issn = {1744-8301},
abstract = {BACKGROUND: Overexpression and/or amplification of human epidermal growth factor receptor 2 (HER2) is a recognized oncogenic driver in metastatic breast cancer (mBC) and metastatic gastric, gastroesophageal junction, or esophageal adenocarcinomas (mGEAC). Although HER2-directed monoclonal antibodies, antibody - drug conjugates (ADCs), and tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of HER2-positive tumors, additional combination regimens and/or novel agents are needed to expand sequential therapy options and improve patient outcomes - particularly following treatment with trastuzumab deruxtecan (T-DXd). Zongertinib is a novel, irreversible, HER2-selective TKI that spares EGFR.

STUDY DESIGN: Here, we detail the rationale and design of Beamion BCGC-1 (NCT06324357), an international Phase Ib/II open-label trial in which patients with previously treated HER2-positive mBC or mGEAC will receive zongertinib alone or in combination. Phase Ib (dose escalation) will determine the maximum tolerated dose of zongertinib plus trastuzumab emtansine (T-DM1), T-DXd, or trastuzumab ± capecitabine, in patients with HER2-positive mBC, and plus T-DXd in patients with HER2-positive mGEAC. Phase II (dose optimization) will assess two doses of zongertinib in combination regimens, or as monotherapy, in patients with mBC or mGEAC. The trial is actively recruiting in six countries globally.

CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT06324357.},
}

@article {pmid40789020,
year = {2025},
author = {Stolla, M and Cap, AP and Spinella, PC},
title = {Chilling controversy: cold-stored platelets for prophylactic transfusions.},
journal = {Blood},
volume = {146},
number = {17},
pages = {2023-2028},
doi = {10.1182/blood.2025029252},
pmid = {40789020},
issn = {1528-0020},
mesh = {Humans ; *Platelet Transfusion/methods ; *Blood Preservation/methods ; *Blood Platelets/cytology ; Cold Temperature ; *Hemorrhage/prevention & control/therapy ; Thrombocytopenia/therapy ; *Cryopreservation/methods ; Platelet Count ; },
abstract = {The US Food and Drug Administration recently licensed 14-day cold-stored platelets for bleeding patients. This policy change represents a reversal from the 1970s when cold-stored platelets were discontinued because of their short circulation time in healthy humans. This change will increase their availability in US hospitals with large trauma populations and in remote and rural settings in the United States. In some of these hospitals, cold-stored platelets will be the only platelets available. It is currently unclear whether patients with hypoproliferative thrombocytopenia who need platelet transfusion for prophylaxis benefit from cold-stored platelets. However, it is noteworthy that in recent clinical trials using room temperature-stored platelets, the transfusion interval in patients with hematologic and oncologic conditions can be as short as 1 transfusion per day, very similar to what one would expect to achieve with cold-stored platelets. Furthermore, the emphasis on the posttransfusion count increment and the platelet count as a transfusion trigger per se is questionable. In the PLADO trial, there was only a poor correlation between the morning platelet count and bleeding events, implicating other factors, such as red blood cells, coagulation factors, and vascular health, as possible culprits. In this perspective article, we review the history of cold platelets and the reason for their discontinuation, focus on recent clinical trial data using room temperature-stored platelets, and review the platelet count as a transfusion trigger. Overall, using cold platelets for prophylaxis may seem counterintuitive, but a closer look at the available data suggests that the indication expansion may hold more promise.},
}

Humans
*Platelet Transfusion/methods
*Blood Preservation/methods
*Blood Platelets/cytology
Cold Temperature
*Hemorrhage/prevention & control/therapy
Thrombocytopenia/therapy
*Cryopreservation/methods
Platelet Count

@article {pmid40729699,
year = {2025},
author = {Shadman, M and Davids, MS},
title = {How I treat patients with CLL after prior treatment with a covalent BTK inhibitor and a BCL-2 inhibitor.},
journal = {Blood},
volume = {146},
number = {17},
pages = {2029-2036},
doi = {10.1182/blood.2024025482},
pmid = {40729699},
issn = {1528-0020},
mesh = {Humans ; *Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy/therapy ; *Agammaglobulinaemia Tyrosine Kinase/antagonists & inhibitors ; *Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors ; *Protein Kinase Inhibitors/therapeutic use ; Male ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use ; Female ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Sulfonamides ; },
abstract = {The treatment landscape for chronic lymphocytic leukemia (CLL) has been transformed by the advent of covalent Bruton tyrosine kinase (BTK) inhibitors (cBTKis) and B-cell lymphoma 2 (BCL-2) inhibitors, leading to markedly improved outcomes and, for many, near-normal life expectancy. However, patients progressing after both classes of therapy (double-refractory) have limited options and poor prognoses. This review outlines a practical approach to managing double-exposed or double-refractory CLL, incorporating clinical cases, trial data, and expert perspectives. For cBTKi intolerance, second-generation agents may remain effective. Venetoclax retreatment is reasonable after prior fixed-duration use. In true double-refractory disease, noncovalent BTK inhibitors (eg, pirtobrutinib) and CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy (lisocabtagene maraleucel) are standard-of-care options. Pirtobrutinib induces rapid responses, though often of limited duration, underscoring the need for early consolidation planning with CAR-T or allogeneic stem cell transplant. Persistent disease after CAR-T therapy warrants close monitoring and timely transplant referral in eligible patients. Phosphoinositide 3-kinase inhibitors remain available but are limited by toxicity and modest benefit. Emerging agents, including BTK degraders, bispecific antibodies, and novel cellular therapies, offer promising future directions. Optimizing outcomes in double-refractory CLL requires an individualized, nuanced strategy integrating available treatments with innovative approaches under investigation.},
}

Humans
*Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy/therapy
*Agammaglobulinaemia Tyrosine Kinase/antagonists & inhibitors
*Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors
*Protein Kinase Inhibitors/therapeutic use
Male
Bridged Bicyclo Compounds, Heterocyclic/therapeutic use
Female
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use
Sulfonamides

@article {pmid41107551,
year = {2025},
author = {Prodanov, T and Plender, EG and Seebohm, G and Meuth, SG and Eichler, EE and Marschall, T},
title = {Locityper enables targeted genotyping of complex polymorphic genes.},
journal = {Nature genetics},
volume = {},
number = {},
pages = {},
pmid = {41107551},
issn = {1546-1718},
support = {R01 HG002385/HG/NHGRI NIH HHS/United States ; R01 HG002385/HG/NHGRI NIH HHS/United States ; },
abstract = {The human genome contains many structurally variable polymorphic loci, including several hundred disease-associated genes, almost inaccessible for accurate variant calling. Here we present Locityper, a tool capable of genotyping such challenging genes using short-read and long-read whole-genome sequencing. For each target, Locityper recruits and aligns reads to locus haplotypes, for instance, extracted from a pangenome, and finds the likeliest haplotype pair by optimizing read alignment, insert size and read depth profiles. Across 256 challenging medically relevant loci, Locityper achieves a median quality value (QV) above 35 from both long-read and short-read data, outperforming state-of-the-art Illumina and PacBio HiFi variant calling pipelines by 10.9 and 1.7 points, respectively. Furthermore, Locityper provides access to hyperpolymorphic HLA genes and other gene families, including KIR, MUC and FCGR. With its low running time of 1 h 35 m per sample at eight threads, Locityper is scalable to biobank-sized cohorts, enabling association studies for previously intractable disease-relevant genes.},
}

@article {pmid41107178,
year = {2025},
author = {Vigneswaran, HT and Palsdottir, T and Micoli, C and Tilki, D and Lin, D and Cooperberg, M and Eggener, S and Falagario, UG and Möller, A and Aly, M and Akre, O and Wiklund, P and Egevad, L and Grönberg, H and Nordström, T and Eklund, M},
title = {Stockholm3 Versus Prostate-specific Antigen in Prostate Cancer Screening: 9-year Outcomes Demonstrating Improved Detection of Aggressive Cancers and Reduced Overdiagnosis from the STHLM3 Trial.},
journal = {European urology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.eururo.2025.10.001},
pmid = {41107178},
issn = {1873-7560},
abstract = {BACKGROUND AND OBJECTIVE: Prostate-specific antigen (PSA) thresholds (≥3 or 4 ng/ml) are used to balance prostate cancer (PCa) detection against false positives; yet, aggressive PCa can occur at a low PSA and indolent tumors at a high PSA level. Long-term data clarifying aggressiveness across PSA thresholds are limited.

METHODS: The STHLM3 screening trial enrolled 59 088 men. All received PSA testing; those with PSA ≥1 ng/ml underwent the multianalyte Stockholm3 blood test. We analyzed men treated with radical prostatectomy or radiotherapy (n = 968). Outcomes were any biochemical recurrence (BCR), high-risk BCR, and PCa-specific mortality. Incidence across four baseline groups-(1) elevated PSA (≥3 ng/ml) and Stockholm3 (≥11), (2) elevated Stockholm3 alone (≥11), (3) elevated PSA alone (≥3 ng/ml), and (4) neither elevated PSA (<3 ng/ml) nor elevated Stockholm3 (<11)-was compared using Gray's test and competing-risk regression.

KEY FINDINGS AND LIMITATIONS: Follow-up was 8.9 yr. The 5-yr cumulative rates of any/high-risk BCR were as follows: 13%/9.0% for both elevated Stockholm3 (≥11) and elevated PSA (≥3 ng/ml), 9.4%/5.3% for elevated Stockholm3 alone, 1.5%/0% for elevated PSA alone, and 0%/0% for nonelevated results on both tests (p < 0.001). Compared with PSA-only elevation, Stockholm3-only elevation showed a hazard ratio (HR) of 1.8 (95% confidence interval 0.8-3.9; p = 0.2) for any BCR and an HR of 8.8 (1.06-72; p = 0.044) for high-risk BCR.

Some men with PSA <3 ng/ml harbor aggressive PCa with a substantial risk of recurrence after upfront curative treatment. Risk predictive blood tests, such as Stockholm3, used at lower PSA thresholds, can identify these men, while few clinically important cancers are missed when biopsy is deferred with PSA ≥3 ng/ml but low Stockholm3 scores.},
}

@article {pmid41106548,
year = {2025},
author = {Khor, S and Basu, A and Shankaran, V and Lee, K and Haupt, EC and Hahn, EE and Carlson, JJ and Bansal, A},
title = {Evaluating Long-term Health Disparity Impacts of Clinical Algorithms Using a Patient-level Simulation Framework.},
journal = {Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jval.2025.09.3066},
pmid = {41106548},
issn = {1524-4733},
abstract = {OBJECTIVE: This study applies a simulation framework to evaluate the long-term effects of omitting race from a colon cancer decision algorithm for adjuvant chemotherapy, assessing impacts on health outcomes, costs, and disparities while accounting for measurement errors across racial groups.

METHODS: We developed a patient-level state-transition model using electronic health records from a large Southern California health system to project outcomes for 4,839 adults with stage II and III colon cancer post-surgery. We compared 30-year quality-adjusted life-years (QALYs), healthcare costs, and QALY distribution among racial groups under three chemotherapy treatment scenarios: 1) current practice, 2) treatment guided by an algorithm that includes race, and 3) the same algorithm with race omitted. An additional health state addressed racial bias in cancer recurrence ascertainment, and probabilistic sensitivity analysis (PSA) assessed uncertainty.

RESULTS: The clinical algorithm, compared to current practice, could improve average health by 0.048 QALYs and reduce racial health disparity by 0.20 QALYs at an incremental cost of $3,221, with the disparity gap decreasing in 96% of PSA iterations. Omitting race showed minimal effects on overall health or costs but resulted in 13% fewer Black patients receiving treatment, decreasing their QALYs by 0.07 and widening the disparity gap by 0.13 QALY. Health disparity increased in 94% of PSA iterations.

CONCLUSIONS: A cancer decision algorithm can improve population health and reduce health disparities, but omitting race may harm disadvantaged groups and limit reductions in disparities. Patient-level simulations can be routinely used to evaluate the potential health disparity impacts of algorithms before implementation.},
}

@article {pmid41106476,
year = {2025},
author = {Chowdhury, S and Gasper, C and Lazar, AA and Allaire, K and Darragh, TM and Fong, L and Palefsky, JM},
title = {Expression of programmed death ligand-1 and programmed cell death-1 across the anal neoplasia disease continuum and association with survival in anal cancer.},
journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc},
volume = {},
number = {},
pages = {100918},
doi = {10.1016/j.modpat.2025.100918},
pmid = {41106476},
issn = {1530-0285},
abstract = {High-risk human papillomavirus (HPV) is associated with anal high-grade intraepithelial lesion (aHSIL) and anal squamous cell carcinoma (aSCC). The prognostic significance of PD-L1 expression in aSCC and its impact on overall survival (OS) is controversial. ASCC can evade immune surveillance by co-opting the PD-L1/PD-1 immune checkpoint pathway, enhancing tumorigenesis. To assess the potential role of the PD-L1/PD-1 axis on tumor progression, we assessed PD-L1 and PD-1 expression on epithelial cells and immune cells by immunohistochemistry in non-lesional anal tissue (n=22), aHSIL (n=22), and aSCC (n=52) from HIV-negative participants and people living with HIV. PD-L1 expression on epithelial cells was restricted to tumor cells with no expression in non-lesional and HSIL tissues, while PD-L1-positive immune cells were present across all three diagnostic stages. PD-1 expression was absent on epithelial cells whereas PD-1-positive immune cells increased along the disease continuum from non-lesional to aSCC. The overall PD-L1 expression on epithelial cells and immune cells measured by the combined positive score (CPS) in aSCC and the aggregate PD-L1 score in non-lesional and HSIL showed a substantial increase from non-lesional to aHSIL to aSCC. In aSCC, PD-L1 expression on immune cells was more prominent than in tumor cells and correlated with increased immune cell infiltration and interferon-gamma secretion. 92% of aSCC exhibited an adaptive PD-L1 expression pattern characterized by PD-L1 expression on tumors cells, immune cells or both. HIV status did not affect PD-L1/PD-1 expression in non-lesional, aHSIL or aSCC. PD-L1 expression in treatment naïve aSCC was associated with improved OS. Those with CPS of 0 had a higher risk of death [Hazard ratio 15.2 (95% CI: 3.3-69, p=0.0004; log-rank p<0.0001)] compared to those with CPS > 0. CPS may indicate the presence of immune activation and serve as a potential prognostic marker.},
}

@article {pmid41106380,
year = {2025},
author = {Galeano Niño, JL and Ponath, F and Ajisafe, VA and Becker, CR and Kempchinsky, AG and Zepeda-Rivera, MA and Gomez, JA and Wu, H and Terrazas, JG and Bouzek, H and Cromwell, E and Chanana, P and Wong, M and Damania, A and White, MG and You, YN and Kopetz, S and Ajami, NJ and Wargo, JA and Johnston, CD and Bullman, S},
title = {Tumor-infiltrating bacteria disrupt cancer epithelial cell interactions and induce cell-cycle arrest.},
journal = {Cancer cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ccell.2025.09.010},
pmid = {41106380},
issn = {1878-3686},
abstract = {Tumor-infiltrating bacteria are increasingly recognized as modulators of cancer progression and therapy resistance. We describe a mechanism by which extracellular intratumoral bacteria, including Fusobacterium, modulate cancer epithelial cell behavior. Spatial imaging and single-cell spatial transcriptomics show that these bacteria predominantly localize extracellularly within tumor microniches of colorectal and oral cancers, characterized by reduced cell density, transcriptional activity, and proliferation. In vitro, Fusobacterium nucleatum disrupts epithelial contacts, inducing G0-G1 arrest and transcriptional quiescence. This state confers 5-fluorouracil resistance and remodels the tumor microenvironment. Findings were validated by live-cell imaging, spatial profiling, mouse models, and a 52-patient colorectal cancer cohort. Transcriptomics reveals downregulation of cell cycle, transcription, and antigen presentation genes in bacteria-enriched regions, consistent with a quiescent, immune-evasive phenotype. In an independent rectal cancer cohort, high Fusobacterium burden correlates with reduced therapy response. These results link extracellular bacteria to cancer cell quiescence and chemoresistance, highlighting microbial-tumor interactions as therapeutic targets.},
}

@article {pmid41106280,
year = {2025},
author = {Tower, A and Owens, K and Esmaeili, S and Schiffer, JT and Reeves, DB and Schwartz, EJ},
title = {Quantitative viral dynamics: Methods for parameter estimation.},
journal = {Virology},
volume = {613},
number = {},
pages = {110631},
doi = {10.1016/j.virol.2025.110631},
pmid = {41106280},
issn = {1096-0341},
abstract = {Fitting mathematical models of viral dynamics to serial, quantitative viral load data provides inferences on the mechanisms in virus infection. This process can reveal the speed and magnitude of viral replication, cell proliferation and death, immune responses, and/or treatment efficacy. Viral dynamics modeling involves developing conceptual models, translating them into equations, and applying the appropriate statistical tools to determine the optimal parameters such that the model recapitulates observations from human and animal infections. In this review, we outline the theoretical foundations needed to understand model fitting, parameter estimation, and what it means to achieve a good fit. We provide examples and explain the strengths and limitations of three commonly used model fitting approaches: individual fitting, population mixed effects fitting, and feature fitting. We briefly review fitting algorithms and highlight powerful available computer software packages that can be used for fitting and parameter estimation. We discuss different model types, parameter identifiability, and how future modeling efforts can leverage advances in multi-dimensional data. Finally, we conclude with simple guidelines for choosing the best approach based on available data and scientific questions.},
}

@article {pmid41105919,
year = {2025},
author = {Ji, X and Hu, X and Nathan, PC and Leisenring, WM and Armstrong, GT and Castellino, SM and Kirchhoff, AC},
title = {Changes in Medicaid Enrollment Among Adult Survivors of Childhood Cancer After Medicaid Expansion: A Report From the Childhood Cancer Survivor Study.},
journal = {JCO oncology practice},
volume = {},
number = {},
pages = {OP2401056},
doi = {10.1200/OP-24-01056},
pmid = {41105919},
issn = {2688-1535},
abstract = {PURPOSE: Little is known about whether Medicaid expansion under the Affordable Care Act affects insurance coverage among adult survivors of childhood cancer, a high-risk population requiring lifetime follow-up care. We examined the association of Medicaid expansion with Medicaid enrollment among participants in the Childhood Cancer Survivor Study.

METHODS: We identified 13,355 adult survivors (age 18-64 years) diagnosed with cancer at age <21 years between 1970 and 1999 and linked these survivors to Medicaid administrative data from 2010 to 2019. Outcomes included the percentage of survivors with any Medicaid enrollment and Medicaid-covered days (total number of days when a survivor was enrolled in Medicaid) each year. Multivariable difference-in-differences (DD) models were used to examine outcome changes (post- v pre-expansion) in expansion versus nonexpansion states.

RESULTS: Medicaid enrollment rates among survivors increased in expansion states (17.1% pre-expansion to 22.8% postexpansion) but decreased in nonexpansion states (16.6%-15.7%), leading to a net increase of 7.1 percentage points (ppts; 95% CI, 6.1 to 8.1). The DD model also showed a net mean increase of 18.7 days/year (95% CI, 15.0 to 22.4) in Medicaid-covered days in expansion relative to nonexpansion states. The expansion-associated increase in enrollment was greatest among survivors who were age 18-29 years (11.2 ppts; 95% CI, 8.3 to 14.1), non-Hispanic Black (13.6 ppts, 95% CI, 8.8 to 18.4) or Hispanic (13.4 ppts, 95% CI, 7.0 to 19.8), with <$20K in US dollars (USD) self-reported household income (13.5 ppts, 95% CI, 10.7 to 16.3), and noncollege graduates (9.3 ppts, 95% CI, 7.7 to 10.9). Similar patterns were observed when examining Medicaid-covered days.

CONCLUSION: To our knowledge, we provide the first evidence of increased Medicaid enrollment and longer coverage duration among adult survivors of childhood cancer after Medicaid expansion. Greater increases were seen among survivors from underrepresented racial/ethnic backgrounds, young adult survivors, and those with lower socioeconomic status, providing a mechanism to reduce disparities and ensure long-term medical care for childhood cancer survivors.},
}

@article {pmid41105890,
year = {2025},
author = {Zwaan, CM and Tasian, SK and Aplenc, R and Brodersen, LE and Buldini, B and De Moerloose, B and Dworzak, MN and Fogelstrand, L and Gibson, BE and Goemans, BF and Hasle, H and Hirsch, BA and Kaspers, GJ and Klusmann, JH and Kutny, MA and Lehrnbecher, T and Locatelli, F and Meshinchi, S and Petit, A and Pigazzi, M and Tierens, A and Kolb, EA and Reinhardt, D and Tomizawa, D and Cooper, TM},
title = {Diagnosis and Management of AML in Pediatric Patients: Consensus Recommendations from an International Expert Panel.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2024027904},
pmid = {41105890},
issn = {1528-0020},
abstract = {The European LeukemiaNet has periodically issued guidelines for the diagnosis and management of acute myeloid leukemia (AML) in adults. These consensus recommendations, most recently updated in 2022, incorporate recent advances in genomic testing, disease detection methods, target identification, and response assessment. Whilst similarities exist between AML in children and adults, pediatric AML is frequently characterized by unique cytogenetic and molecular features, which require distinct genetic and immunophenotypic diagnostics, therapeutic approaches, response assessment criteria, and supportive care strategies. To address these specific needs, an international panel of pediatric hematologist-oncologists, biologists, geneticists, and laboratory medicine scientists convened to develop recommendations for the diagnosis and management of AML in children, adolescents, and young adults (hereafter termed pediatric AML) that are discussed in this special report.},
}

@article {pmid41105630,
year = {2025},
author = {Beyrer, C and Remien, RH and Eshleman, SH and Gamble, TR and De Dieu Tapsoba, J and Labbett, RL and Sullivan, PA and Laeyendecker, O and Anderson, PL and Agravat, D and Hughes, JP and Driffin, DD and Hutchinson, CS and Hucks-Ortiz, C and Adair, M and Curry, M and Jones, SB and Haddock, IL and Boyd, D and Burwen, DR and Johnson, AS and Nelson, LE and , },
title = {Investigating the HIV epidemic among Black gay and bisexual men in the Southern United States: Results of the HPTN 096 pilot cross-sectional assessment.},
journal = {PloS one},
volume = {20},
number = {10},
pages = {e0334031},
pmid = {41105630},
issn = {1932-6203},
mesh = {Humans ; Male ; *HIV Infections/epidemiology/prevention & control/drug therapy ; Cross-Sectional Studies ; Adult ; *Homosexuality, Male/statistics & numerical data ; Pilot Projects ; *Black or African American/statistics & numerical data ; Middle Aged ; United States/epidemiology ; Pre-Exposure Prophylaxis ; *Bisexuality/statistics & numerical data ; Young Adult ; Adolescent ; Incidence ; *Epidemics ; White ; },
abstract = {BACKGROUND: The HIV Prevention Trials Network (HPTN) 096 study was designed to address the markedly higher rates of HIV incidence among Black men who have sex with men (MSM) in the Southern United States (US). A cross-sectional assessment was conducted during the pilot phase of the study to determine its feasibility and collect key HIV-related metrics for the study population.

METHODS AND FINDINGS: Four hundred and twenty-two Black MSM, ≥ 15 years old and living in the four pilot communities (Dallas, TX; Houston, TX; Montgomery, AL; Greenville, SC), were enrolled via starfish sampling into the cross-sectional assessment. Each participant completed two questionnaires and had blood samples collected at a single study visit. Laboratory testing was performed to determine HIV status and use of oral pre-exposure prophylaxis (PrEP). HIV drug resistance and viral suppression were also assessed for two of the four pilot communities (Dallas and Houston). Categorical variables were summarized using frequency and percentage. Continuous variables were summarized using mean, standard deviation, median and interquartile range. Univariable and multivariable logistic regression models were used to assess various associations. HIV status was determined for 403 of the 422 participants (95.5%); 212 (52.6%) men were living with HIV, including one with acute HIV. For these participants, 163 (76.9%) reported that they were in HIV care. In Dallas and Houston, 71 of the 101 living with HIV (70.3%) were virally suppressed. Of the 191 not living with HIV, 57 (29.8%) reported ever taking PrEP, 41 (21.5%) reported being currently on PrEP, and eight (4.2%) reported never having heard of PrEP. PrEP use was documented through laboratory testing in 36 (19.1%) of 188 participants tested; of the 41 participants reporting current PrEP use, five did not have laboratory evidence of PrEP use.

CONCLUSION: During the pilot, we successfully recruited Black MSM using starfish sampling and demonstrated the feasibility of collecting primary study outcomes using a cross-sectional assessment. We found a high burden of HIV and those living with HIV had only a moderate rate of viral suppression. In addition, PrEP use was uncommon among the men living without HIV. Reducing HIV incidence in Black MSM remains a key element to addressing the HIV epidemic in the US.},
}

Humans
Male
*HIV Infections/epidemiology/prevention & control/drug therapy
Cross-Sectional Studies
Adult
*Homosexuality, Male/statistics & numerical data
Pilot Projects
*Black or African American/statistics & numerical data
Middle Aged
United States/epidemiology
Pre-Exposure Prophylaxis
*Bisexuality/statistics & numerical data
Young Adult
Adolescent
Incidence
*Epidemics
White

@article {pmid41105497,
year = {2025},
author = {Gavate, R and Zepeda-Rivera, MA and Jones, DS and LaCourse, KD and Bullman, S and Johnston, CD},
title = {Complete genome sequence of Peptostreptococcus anaerobius SB204, isolated from a human colonic adenocarcinoma.},
journal = {Microbiology resource announcements},
volume = {},
number = {},
pages = {e0080425},
doi = {10.1128/mra.00804-25},
pmid = {41105497},
issn = {2576-098X},
abstract = {We report the complete genome sequence of Peptostreptococcus anaerobius SB204, a strain isolated from the resected tumor of a treatment-naive patient with colorectal cancer. The genome comprises a single chromosomal contig of 2.15 Mbp with an overall GC content of 36.1%.},
}

@article {pmid41104107,
year = {2025},
author = {Tom, A and Gomez-Acosta, C and Henderson, V and McDougall, J and Mendoza, JA and Carosso, E and Cohn, EB and Barrington, WE and Bigelow-Chavez, L and Nyame, YA and Lion, KC},
title = {Advancing equity in cancer care: a pilot explanatory mixed methods study of a racially, ethnically, and linguistically concordant model of patient navigation.},
journal = {Journal of health equity},
volume = {2},
number = {1},
pages = {},
pmid = {41104107},
issn = {2994-4694},
support = {F31 CA157045/CA/NCI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; T32 CA092408/CA/NCI NIH HHS/United States ; },
abstract = {Disparities in cancer outcomes persist among systemically marginalized patients. A new racially, ethnically, or linguistically concordant (RELC) model of patient navigation (PN) was piloted at Fred Hutchinson Cancer Center in 2019. An explanatory mixed-methods observational study assessed patient-centered outcomes of RELC PN, traditional PN, and no PN. Patients from these models completed surveys at baseline and follow-up to measure changes in satisfaction, discrimination, resilience, stress, trust, and discussion of clinical trials. Interviews with patients receiving RELC PN were analyzed using thematic analysis. A total of 118 participants completed surveys. Satisfaction with care improved by 4.2 points (SD 7.0) on an 18-item 5-point Likert scale for those receiving RELC navigation, with no change in traditional or no PN groups. Discrimination based on race dropped from 40% (n = 2) to 20% (n = 1) in the RELC model. A higher proportion of RELC PN patients (80%; n = 4) discussed clinical trials compared to traditional PN (17%; n = 3) and no PN (20% n = 19). Thematic analysis of 29 interviews indicated the model was crucial in overcoming racism, improving trust, and empowering patients. This study highlights the potential of RELC PN to improve patient satisfaction, increase participation in clinical trials, and reduce experiences of discrimination.},
}

@article {pmid41103457,
year = {2025},
author = {Zhu, K and Zheng, Y and Chan, KCG},
title = {Weighted Brier Score - an Overall Summary Measure for Risk Prediction Models with Clinical Utility Consideration.},
journal = {Statistics in biosciences},
volume = {},
number = {},
pages = {},
pmid = {41103457},
issn = {1867-1764},
support = {R01 CA236558/CA/NCI NIH HHS/United States ; U24 CA086368/CA/NCI NIH HHS/United States ; },
abstract = {As advancements in novel biomarker-based algorithms and models accelerate their use in disease risk prediction, it is crucial to evaluate these models within the context of their intended clinical application. Prediction models output the absolute risk of disease; subsequently, patient counseling and shared decision-making are based on the estimated individual risk and cost-benefit assessment. The overall impact of the application is referred to as clinical utility, which received significant attention and desire to incorporate into model assessment lately. The classic Brier score is a popular measure of prediction accuracy; however, it is insufficient for effectively assessing clinical utility. To address this limitation, we propose a class of weighted Brier scores that aligns with the decision-theoretic framework of clinical utility. Additionally, we decompose the weighted Brier score into discrimination and calibration components, and we link the weighted Brier score to the H measure, which has been proposed as an alternative to the area under the receiver operating characteristic curve. This theoretical link to the H measure further supports our weighting method and underscores the essential elements of discrimination and calibration in risk prediction evaluation. The practical use of the weighted Brier score as an overall summary is demonstrated using data from a prostate cancer study.},
}

@article {pmid41102612,
year = {2025},
author = {Heldman, MR and Boeckh, MJ and Ison, MG},
title = {Influenza Antivirals for Prevention and Treatment in Immunocompromised People.},
journal = {The Journal of infectious diseases},
volume = {232},
number = {Supplement_3},
pages = {S243-S253},
doi = {10.1093/infdis/jiaf217},
pmid = {41102612},
issn = {1537-6613},
mesh = {Humans ; *Immunocompromised Host ; *Influenza, Human/prevention & control/drug therapy ; *Antiviral Agents/therapeutic use ; Dibenzothiepins/therapeutic use ; Neuraminidase/antagonists & inhibitors ; Pyridones/therapeutic use ; Thiepins/therapeutic use ; Morpholines ; Pyridines/therapeutic use ; Drug Resistance, Viral ; Triazines ; },
abstract = {Antivirals form a foundation for protecting immunocompromised individuals (ICIs) from influenza complications. Neuraminidase inhibitors have demonstrated benefit for both prophylaxis and treatment in ICIs, including when given >48 hours after symptom onset. Baloxavir is a newer antiviral that has potent effects on viral kinetics in immunocompetent people, but data on baloxavir in ICIs are currently limited. Optimization of antiviral therapy to minimize viral replication within ICIs and reduce the risk of treatment-emergent antiviral resistance (eg, through combination regimens) may prevent viral evolution within ICIs and mitigate transmission of virulent or resistant variants to the general public. Unfortunately, ICIs have been excluded from most clinical trials evaluating novel influenza preventive and therapeutic strategies. Inclusion of ICIs in such clinical trials is essential to facilitate acquisition of clinical and virologic data in patients with specific immunocompromising conditions and ensure that ICIs have equitable access to valuable interventions.},
}

Humans
*Immunocompromised Host
*Influenza, Human/prevention & control/drug therapy
*Antiviral Agents/therapeutic use
Dibenzothiepins/therapeutic use
Neuraminidase/antagonists & inhibitors
Pyridones/therapeutic use
Thiepins/therapeutic use
Morpholines
Pyridines/therapeutic use
Drug Resistance, Viral
Triazines

@article {pmid41102222,
year = {2025},
author = {Ellison, ST and Hayman, I and Derr, K and Derr, P and Frebert, S and Itkin, Z and Shen, M and Jones, A and Olson, W and Corey, L and Wald, A and Johnston, C and Fong, Y and Ferrer, M and Zhu, J},
title = {Limitations of acyclovir and identification of potent HSV antivirals using 3D bioprinted human skin equivalents.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {9200},
pmid = {41102222},
issn = {2041-1723},
support = {U18 TR0033208//U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS)/ ; T32 AI007140/AI/NIAID NIH HHS/United States ; U18 TR003208/TR/NCATS NIH HHS/United States ; T32 AI07140//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; R01 AI143773/AI/NIAID NIH HHS/United States ; },
mesh = {Humans ; *Antiviral Agents/pharmacology ; *Acyclovir/pharmacology ; Keratinocytes/drug effects/virology ; *Skin/cytology/drug effects/virology ; Fibroblasts/drug effects/virology ; Printing, Three-Dimensional ; *Herpes Simplex/drug therapy/virology ; Bioprinting/methods ; *Simplexvirus/drug effects ; Virus Replication/drug effects ; },
abstract = {Herpes simplex virus (HSV) infection poses global public health concerns with lifelong impacts. Acyclovir, the standard therapy, has limited efficacy in preventing subclinical shedding, and drug resistance occurs in immunocompromised patients, highlighting the need for novel therapeutics. Here we show that acyclovir is significantly less effective in skin-derived keratinocytes than donor-matched fibroblasts. Using 3D bioprinted human skin equivalents (HSEs) in a 96-well plate format, we have screened 738 compounds with broad targets and mechanisms of action, identifying potent antivirals, including 23 known or experimental HSV treatments. Unlike acyclovir, antivirals against HSV helicase/primase or host replication pathways display similar potency across cell types and donor sources in both 2D and 3D models. The reduced potency in keratinocytes may explain acyclovir's limited clinical efficacy. Our 3D bioprinted HSE assay platform enables the integration of patient-derived cells early in drug development and offers a physiologically relevant approach for HSV drug discovery.},
}

Humans
*Antiviral Agents/pharmacology
*Acyclovir/pharmacology
Keratinocytes/drug effects/virology
*Skin/cytology/drug effects/virology
Fibroblasts/drug effects/virology
Printing, Three-Dimensional
*Herpes Simplex/drug therapy/virology
Bioprinting/methods
*Simplexvirus/drug effects
Virus Replication/drug effects

@article {pmid41102182,
year = {2025},
author = {Weinstock, JS and Chaudhry, SA and Ioannou, M and Viskadourou, M and Reventun, P and Jakubek, YA and Liggett, LA and Laurie, C and Broome, JG and Khan, A and Taylor, KD and Guo, X and Peyser, PA and Boerwinkle, E and Chami, N and Kenny, EE and Loos, RJ and Psaty, BM and Tracy, RP and Brody, JA and Yun, JH and Cho, MH and Vasan, RS and Kardia, SL and Smith, JA and Raffield, LM and Bidulescu, A and O'Brien, EC and de Andrade, M and Rotter, JI and Rich, SS and Tracy, RP and Chen, YI and Gu, CC and Hsiung, CA and Kooperberg, C and Haring, B and Nassir, R and Mathias, R and Reiner, A and Sankaran, VG and Lowenstein, CJ and Blackwell, TW and Abecasis, GR and Smith, AV and Kang, HM and Natarajan, P and Jaiswal, S and Bick, A and Post, WS and Scheet, P and Auer, P and Karantanos, T and Battle, A and Arvanitis, M},
title = {Genetic determinants and genomic consequences of non-leukemogenic somatic point mutations.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {9194},
pmid = {41102182},
issn = {2041-1723},
support = {R01 HL120393/HL/NHLBI NIH HHS/United States ; K08 HL166690/HL/NHLBI NIH HHS/United States ; U01 HL120393/HL/NHLBI NIH HHS/United States ; R35 GM139580/GM/NIGMS NIH HHS/United States ; R01 HL117626/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *Point Mutation/genetics ; Genome-Wide Association Study ; *Clonal Hematopoiesis/genetics ; Genomics/methods ; Germ-Line Mutation ; },
abstract = {Clonal hematopoiesis (CH) is defined by the expansion of a lineage of genetically identical cells in blood. Genetic lesions that confer a fitness advantage, such as leukemogenic point mutations or mosaic chromosomal alterations (mCAs), are frequent mediators of CH. However, recent analyses of both single cell-derived colonies of hematopoietic cells and population sequencing cohorts have revealed CH frequently occurs in the absence of known driver genetic lesions. To characterize CH without known driver genetic lesions, we use 51,399 deeply sequenced whole genomes from the NHLBI TOPMed sequencing initiative to perform simultaneous germline and somatic mutation analyses among individuals without leukemogenic point mutations (LPM), which we term CH-LPMneg. We quantify CH by estimating the total mutation burden. Because estimating somatic mutation burden without a paired-tissue sample is challenging, we develop a novel statistical method, the Genomic and Epigenomic informed Mutation (GEM) rate, that uses external genomic and epigenomic data sources to distinguish artifactual signals from true somatic mutations. We perform a genome-wide association study of GEM to discover the germline determinants of CH-LPMneg. We identify seven genes associated with CH-LPMneg (TCL1A, TERT, SMC4, NRIP1, PRDM16, MSRA, SCARB1).Functional analyses of SMC4 and NRIP1 implicated altered hematopoietic stem cell self-renewal and proliferation as the primary mediator of mutation burden in blood. We then perform comprehensive multi-tissue transcriptomic analyses, finding that the expression levels of 404 genes are associated with GEM. Finally, we perform phenotypic association meta-analyses across four cohorts, finding that GEM is associated with increased white blood cell count, but is not significantly associated with incident stroke or coronary disease events. Overall, we develop GEM for quantifying mutation burden from WGS and use GEM to discover the genetic, genomic, and phenotypic correlates of CH-LPMneg.},
}

Humans
*Point Mutation/genetics
Genome-Wide Association Study
*Clonal Hematopoiesis/genetics
Genomics/methods
Germ-Line Mutation

@article {pmid41101975,
year = {2025},
author = {Miller, SR and Chung, DH and Gonzalez, RT and Jackson, WC and Caram, MEV and Tsao, PA and Stensland, K and Gulati, R and Shah, Y and Wale, D and Elliott, D and Caverly, T and Hofer, TP and Saini, S and Green, MD and Schipper, M and Dess, RT and Bryant, AK},
title = {Impact of PSMA PET Staging on Initial Treatment in Newly Diagnosed Prostate Cancer.},
journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine},
volume = {},
number = {},
pages = {},
doi = {10.2967/jnumed.125.270825},
pmid = {41101975},
issn = {1535-5667},
abstract = {Prostate-specific membrane antigen (PSMA) PET/CT has become a common staging modality for newly diagnosed high-risk and unfavorable intermediate-risk prostate cancer after showing improved sensitivity and specificity compared with conventional imaging in clinical trials. We aimed to assess the causal impact of PSMA PET staging on initial treatment selection in real-world practice. Methods: We used observational data from the U.S. Veterans Health Administration to emulate a randomized controlled trial in which patients with newly diagnosed, unfavorable intermediate-, high-, and very-high-risk prostate cancer from January 2022 to December 2023 would have been randomized to undergo either upfront [18]F- or [68]Ga-PSMA PET staging or conventional imaging ([99m]Tc bone scan and pelvic CT or MRI). Outcomes of interest included use of frontline androgen deprivation therapy (ADT), second-generation androgen receptor pathway inhibitors (ARPIs), radiotherapy, and radical prostatectomy. Weighted univariable Cox regression was performed to assess the effect of treatment group on each outcome, and 95% CIs were generated from 1,000 bootstrap replicates. Results: In total, 9,049 patients met the criteria for inclusion. PSMA PET staging was associated with higher rates of any ADT use relative to conventional staging (adjusted hazard ratio [aHR], 1.26; 95% CI, 1.19-1.44), higher rates of ARPI use (aHR, 1.52; 95% CI, 1.33-1.78), lower rates of prostatectomy (aHR, 0.69; 95% CI, 0.56-0.83), and no significant effect on the use of radiotherapy (aHR, 1.10; 95% CI, 0.99-1.25). Compared with patients with PSMA stage N0M0, ARPI use was more common in patients with PSMA stage N1M0 (aHR, 6.87; 95% CI, 5.41-8.73) and PSMA stage M1 (aHR, 10.13; 95% CI, 8.16-1.2.58). Patients with PSMA N1M0 disease were much less likely to undergo prostatectomy compared with PSMA N0M0. Conclusion: PSMA PET staging may be leading to fewer prostatectomies and higher use rates of ADT and ARPIs in the Veterans Health Administration.},
}

@article {pmid41101869,
year = {2025},
author = {Apisarnthanarax, S and Kim, EY},
title = {SBRT: The Most Precise and Least Invasive Tool in the Liver Cancer Toolbox.},
journal = {International journal of radiation oncology, biology, physics},
volume = {123},
number = {4},
pages = {919},
doi = {10.1016/j.ijrobp.2025.08.023},
pmid = {41101869},
issn = {1879-355X},
}

@article {pmid41101390,
year = {2025},
author = {Chen, J and Belew, MD and Wei, J and Chow, EJ and Cheng, Z},
title = {Pediatric doxorubicin exposure induces persistent pathological changes in mice.},
journal = {Toxicology and applied pharmacology},
volume = {505},
number = {},
pages = {117600},
doi = {10.1016/j.taap.2025.117600},
pmid = {41101390},
issn = {1096-0333},
abstract = {Over 50 % of pediatric cancer patients undergo treatment with chemotherapy regimens containing anthracyclines, such as doxorubicin (DOX). However, the long-term effects of childhood DOX exposure remain poorly understood, and protective strategies are limited. To establish a mouse model that recapitulates the chronic health conditions in adult survivors of childhood cancer, 14-day-old C57BL/6N mice received DOX (2.5 mg/kg, twice weekly for 2 weeks, i.p.) and were monitored for 32 weeks. Pediatric DOX injection induced late cardiotoxicity including systolic and diastolic dysfunction, cardiac fibrosis and cardiomyocyte atrophy, which were alleviated by treatment with the CDK7/12/13 inhibitor THZ1. Pediatric DOX also reduced heart, liver and spleen weight, while sparing the lung and kidney. Mechanistically, DOX induced persistent activation of p38 in the heart and diminished physiological cardiomyocyte hypertrophy. Pediatric DOX caused slow body weight gain and late mortality, which were surprisingly exacerbated by THZ1. Notably, pediatric THZ1 exposure also hindered body weight gain and reduced heart and liver weight. In conclusion, pediatric DOX exposure resulted in chronic cardiac dysfunction, underweight and premature death during adulthood in mice. Pharmacologic inhibition of CDK7/12/13 with THZ1 partially protected against pediatric DOX-induced cardiotoxicity, but aggravated growth delay and accelerated mortality.},
}

@article {pmid41100801,
year = {2025},
author = {Neelapu, SS and Chavez, JC and Sehgal, AR and Epperla, N and Ulrickson, ML and Bachy, E and Munshi, PN and Casulo, C and Maloney, DG and de Vos, S and Reshef, R and Leslie, LA and Oluwole, OO and Yakoub-Agha, I and Khanal, R and Rosenblatt, JD and Wulff, J and Shen, RR and Zhang, W and Poddar, S and Miao, H and Nikolajeva, O and Jacobson, CA},
title = {Five-Year Follow-Up Analysis of ZUMA-5: Axicabtagene Ciloleucel in Relapsed/Refractory Indolent Non-Hodgkin Lymphoma.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2500668},
doi = {10.1200/JCO-25-00668},
pmid = {41100801},
issn = {1527-7755},
abstract = {Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) follicular lymphoma (FL). Here, we report updated clinical outcomes from ZUMA-5 in 159 enrolled patients with R/R indolent non-Hodgkin lymphoma (iNHL; 127 with FL and 31 with marginal zone lymphoma) after a median follow-up of 64.6 months. Patients underwent leukapheresis and received lymphodepleting chemotherapy and axi-cel (2 × 10[6] CAR T cells/kg). The overall response rate was 90% (75% complete response rate). The median duration of response was 60.4 months, and the median progression-free survival (PFS) was 62.2 months; median time to next treatment and overall survival were not reached (NR). At data cutoff, 55% of patients were alive without requiring subsequent anticancer therapy. Median lymphoma-specific PFS in patients with FL was NR; 34% had progression or death due to lymphoma or study treatment. Notably, after 30 months postinfusion, progression or lymphoma-related deaths were rare. Late-onset toxicities were infrequent and largely unrelated to axi-cel. Durable response and prolonged survival in FL were associated with robust early CAR T-cell expansion and naïve product phenotype. These findings confirm sustained responses and manageable safety with axi-cel in the long term among patients with R/R iNHL and its potential as a curative therapy in FL.},
}

@article {pmid41100668,
year = {2025},
author = {Visani, GM and Pun, MN and Minervina, AA and Bradley, P and Thomas, PG and Nourmohammad, A},
title = {T cell receptor specificity landscape revealed through de novo peptide design.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {42},
pages = {e2504783122},
doi = {10.1073/pnas.2504783122},
pmid = {41100668},
issn = {1091-6490},
support = {R35GM142795//HHS | National Institutes of Health (NIH)/ ; R35 GM141457/GM/NIGMS NIH HHS/United States ; AI136514//HHS | National Institutes of Health (NIH)/ ; A153352//UW | Office of Research Central, University of Washington (ORC)/ ; 2045054//National Science Foundation (NSF)/ ; PHY-2210452//National Science Foundation (NSF)/ ; PHY-2309135//National Science Foundation (NSF)/ ; 2919.02//Gordon and Betty Moore Foundation (GBMF)/ ; },
mesh = {*Receptors, Antigen, T-Cell/immunology/metabolism/chemistry ; *Peptides/immunology/chemistry ; Humans ; Machine Learning ; T-Lymphocytes/immunology ; Major Histocompatibility Complex ; Histocompatibility Antigens Class I/immunology ; Protein Binding ; },
abstract = {T cells play a key role in adaptive immunity by mounting specific responses against diverse pathogens. Effective bindings between T cell receptors (TCRs) and pathogen derived peptides presented on major histocompatibility complexes (MHCs) mediate immune responses. However, predicting these interactions remains challenging due to limited functional data on T cell reactivities. Here, we introduce a computational approach to predict TCR interactions with peptides presented on MHC-I alleles, and to design immunogenic peptides for specified TCR-MHC complexes. Our method leverages HERMES, a structure-based machine learning model trained on the protein universe to predict amino acid preferences based on local structural environments. Despite no direct training on TCR-pMHC data, HERMES's implicit physical reasoning enables us to make accurate predictions of both TCR-pMHC binding affinities and T cell activities across diverse viral and cancer epitopes, achieving up to 0.72 correlation with experimental data. Leveraging our TCR recognition model, we develop a computational protocol for de novo design of immunogenic peptides. Through experimental validation in three TCR-MHC systems, we demonstrate that our designs-with up to five substitutions from the native sequence-activate T cells at success rates of up to 50%. Last, we use our generative framework to quantify the diversity of the peptide recognition landscape for various TCR-MHC's, offering key insights into T cell specificity. Our approach provides a platform for immunogenic peptide and neoantigen design, as well as for evaluating TCR specificity, offering a computational framework to inform design of engineered T cell therapies and vaccines.},
}

*Receptors, Antigen, T-Cell/immunology/metabolism/chemistry
*Peptides/immunology/chemistry
Humans
Machine Learning
T-Lymphocytes/immunology
Major Histocompatibility Complex
Histocompatibility Antigens Class I/immunology
Protein Binding

@article {pmid41099706,
year = {2025},
author = {Hu, C and Popchock, AR and Latino, AA and Asbury, CL and Biggins, S},
title = {Direct observation of interdependent and hierarchical kinetochore assembly on individual centromeres.},
journal = {Nucleic acids research},
volume = {53},
number = {19},
pages = {},
pmid = {41099706},
issn = {1362-4962},
support = {P30 CA015704/CA/NCI/HH/HHS/United States ; R35 GM149357/GM/NIGMS/NH/NIH HHS/United States ; F32GM136010/NH/NIH HHS/United States ; //Jane Coffin Childs Memorial Fund/ ; /HHMI/Howard Hughes Medical Institute/United States ; },
mesh = {*Kinetochores/metabolism ; *Saccharomyces cerevisiae Proteins/metabolism/genetics ; *Centromere/metabolism/genetics ; Saccharomyces cerevisiae/genetics/metabolism ; DNA-Binding Proteins/metabolism/genetics ; Chromosomal Proteins, Non-Histone/metabolism/genetics ; Microtubules/metabolism ; Protein Binding ; Cell Cycle Proteins ; },
abstract = {Kinetochores are megadalton protein machines that harness microtubules to segregate chromosomes during cell division. The kinetochores must assemble after DNA replication during every cell cycle onto specialized regions of chromosomes called centromeres, but the order and regulation of their assembly remains unclear due to the complexity of kinetochore composition and the difficulty resolving individual kinetochores in vivo. Here, by adapting a prior single-molecule method for monitoring kinetochore assembly in budding yeast lysates, we identify a sequential order of assembly and uncover previously unknown interdependencies between subcomplexes. We show that inner kinetochore assembly depends partly on outer kinetochore components, and that outer kinetochore branches do not assemble independently of one another. Notably, Mif2 assembly is a rate-limiting step that can be accelerated by binding to the Mtw1 subcomplex, thereby promoting rapid assembly of many inner and outer kinetochore components. The importance of controlling kinetochore assembly kinetics is supported by a Mif2 mutant lacking both autoinhibition and Mtw1 subcomplex binding activity, which leads to defective kinetochore-microtubule attachments when the centromeric histone variant Cse4 is overexpressed. Altogether, our work provides a direct view of kinetochore assembly and reveals highly interdependent regulatory events that control its order and timing.},
}

*Kinetochores/metabolism
*Saccharomyces cerevisiae Proteins/metabolism/genetics
*Centromere/metabolism/genetics
Saccharomyces cerevisiae/genetics/metabolism
DNA-Binding Proteins/metabolism/genetics
Chromosomal Proteins, Non-Histone/metabolism/genetics
Microtubules/metabolism
Protein Binding
Cell Cycle Proteins

@article {pmid41099265,
year = {2025},
author = {McKenney, JK and Brooks, JD and Nguyen, JK and Ding, CKC and Newcomb, LF and Myles, JL and Alaghehbandan, R and Przybycin, CG and Chan, E and Simko, JP and Greenland, NY and Schwen, Z and Weight, CJ and Cooperberg, MR and Carroll, PR},
title = {In reply to: 'Prostate cancer with favorable histology is not synonymous with prostate cancer indolence'.},
journal = {Histopathology},
volume = {},
number = {},
pages = {},
doi = {10.1111/his.70023},
pmid = {41099265},
issn = {1365-2559},
}

@article {pmid41098153,
year = {2025},
author = {Ikoma-Colturato, MRV and Magalhães Furtado, F and Bertolucci, CM and Severino, AR and Souto, EX and Ferreira Dos Santos, TC and Dametto, APF and Beltrame, MP and Bacal, NS and Avelar, DMV and Fernandes, RA and Gomes, BE and da Costa, ES and Santos, BEFDS and Mendonça de Pontes, R and Périco, MDH and Gevert, F and de Siqueira, PFR and Marquezotti, F and Wagner, AOM and Soares, ACCV and Duarte, FB and Flowers, ME and Vigorito, AC},
title = {Standardization of Measurable Residual Disease in Acute Myeloid Leukemia by Flow Cytometry: A Multicenter Study.},
journal = {EJHaem},
volume = {6},
number = {5},
pages = {e70163},
pmid = {41098153},
issn = {2688-6146},
abstract = {INTRODUCTION: Measurable residual disease (MRD) is a strong predictor of the risk of relapse of acute myeloid leukemia (AML). Therefore, for use in clinical decision-making, methods for MRD assessment must achieve adequate accuracy, sensitivity, specificity, and reproducibility. Multiparametric flow cytometry (MFC) is the most widely used method for assessing AML-MRD, but its sensitivity varies considerably due to the differing approaches used across centers, in addition to the different experiences of flow cytometrists, especially during clonal evolution. This study aimed to standardize AML-MRD by MFC in a multicenter project involving 16 Brazilian laboratories.

METHODS: In the first phase, specialists were trained in pre-analytical standard operating procedures (SOPs) and analysis strategies of pre-validated 8- and 10-color protocols, followed by a data-only, that is, a Dry Phase of flow cytometry standard (FCS) file exchange by the coordinating laboratory in a comparability assessment. In the second or Wet Phase, laboratories prepared and analyzed their samples, and the FCS files were submitted for central analysis.

RESULTS: The agreement of MRD results was 81% and 80% between laboratories and central analysts in the Dry and Wet Phases, respectively. However, non-suitable application of pre-analytical SOPs hampered MRD interpretation for 30% of the laboratories in the Wet Phase.

CONCLUSIONS: This study demonstrated that standardized flow cytometry protocols are reproducible as long as rigorous SOPs are implemented. The project's results underscore that continuous education and external quality control are essential to build expertise and ensure reliable AML-MRD results in clinical practice. Trial Registration:The authors have confirmed clinical trial registration is not needed for this submission.},
}

@article {pmid41096533,
year = {2025},
author = {Munarriz, D and López-Godino, O and Martinez-Cibrian, N and Albiol, N and Brillembourg, H and Navarro-Velázquez, S and Español-Rego, M and Casanueva, S and García-Tomás, L and Muñoz-Sanchez, G and Alserawan, L and Benitez-Ribas, D and Magnano, L and Correa, JG and Rivero, A and Mozas, P and Gine, E and Rodríguez-Lobato, LG and Martínez-Roca, A and Montoro-Lorite, M and Ayora, P and Esteve, J and Frutos, L and Balagué-Ponz, O and Urbano-Ispizua, A and González-Navarro, EA and Juan, M and Delgado, J and Ortiz-Maldonado, V},
title = {Combining CAR T-Cell Therapy and Nivolumab to Overcome Immune Resistance in THRLBCL: A Case Report.},
journal = {International journal of molecular sciences},
volume = {26},
number = {19},
pages = {},
pmid = {41096533},
issn = {1422-0067},
mesh = {Humans ; Female ; Adult ; *Nivolumab/therapeutic use ; *Lymphoma, Large B-Cell, Diffuse/therapy/immunology/pathology ; *Immunotherapy, Adoptive/methods ; *Antineoplastic Agents, Immunological/therapeutic use ; Antigens, CD19/immunology ; B7-H1 Antigen/metabolism ; Combined Modality Therapy ; Drug Resistance, Neoplasm ; Tumor Microenvironment ; },
abstract = {T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a rare, aggressive subtype of diffuse large B-cell lymphoma characterized by a profoundly immunosuppressive tumor microenvironment. PD-L1 overexpression by tumor cells is a recognized immune escape mechanism and may underlie resistance to cellular therapies, including CAR T-cell therapy. We report a case of a 29-year-old woman with refractory stage IV-B THRLBCL treated with anti-CD19 CAR T-cell therapy (varnimcabtagene autoleucel), who achieved an initial response (day +28) but experienced disease progression by day +100 despite robust CAR T-cell expansion. Peripheral blood analysis revealed persistent absolute B-cell aplasia, while bone marrow biopsy confirmed CD19-positive disease. Comparative immunohistochemistry demonstrated markedly increased PD-L1 expression in post-CAR T-cell samples, suggesting adaptive immune resistance via PD-1/PD-L1-mediated CAR T-cell inhibition. Nivolumab was initiated at month +4 to overcome this checkpoint-mediated resistance. Notably, a complete metabolic response was documented on PET/CT after four doses of nivolumab (month +6). The patient remains in sustained remission, with persistent B-cell aplasia, four years post-intervention. This case provides clinical and pathological evidence supporting the use of immune checkpoint blockade to rescue CAR T-cell efficacy, highlighting the potential of this synergistic approach in THRLBCL and possibly other B-cell malignancies exhibiting similar immune evasion.},
}

Humans
Female
Adult
*Nivolumab/therapeutic use
*Lymphoma, Large B-Cell, Diffuse/therapy/immunology/pathology
*Immunotherapy, Adoptive/methods
*Antineoplastic Agents, Immunological/therapeutic use
Antigens, CD19/immunology
B7-H1 Antigen/metabolism
Combined Modality Therapy
Drug Resistance, Neoplasm
Tumor Microenvironment

@article {pmid41093689,
year = {2025},
author = {Goetz, MP and Toi, M and Huober, J and Sohn, J and Trédan, O and Park, IH and Campone, M and Chen, SC and Manso, LM and Paluch-Shimon, S and Freedman, OC and O'Shaughnessy, J and Pivot, X and Tolaney, SM and Hurvitz, SA and Llombart-Cussac, A and André, V and Saha, A and van Hal, G and Shahir, A and Iwata, H and Johnston, SRD},
title = {Corrigendum to "Abemaciclib plus a nonsteroidal aromatase inhibitor as initial therapy for HR+, HER2- advanced breast cancer: final overall survival results of MONARCH 3": [Ann Oncol 2024; 35: 718-727].},
journal = {Annals of oncology : official journal of the European Society for Medical Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.annonc.2025.07.002},
pmid = {41093689},
issn = {1569-8041},
}

@article {pmid41092928,
year = {2025},
author = {, },
title = {Global burden of 292 causes of death in 204 countries and territories and 660 subnational locations, 1990-2023: a systematic analysis for the Global Burden of Disease Study 2023.},
journal = {Lancet (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.1016/S0140-6736(25)01917-8},
pmid = {41092928},
issn = {1474-547X},
abstract = {BACKGROUND: Timely and comprehensive analyses of causes of death stratified by age, sex, and location are essential for shaping effective health policies aimed at reducing global mortality. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides cause-specific mortality estimates measured in counts, rates, and years of life lost (YLLs). GBD 2023 aimed to enhance our understanding of the relationship between age and cause of death by quantifying the probability of dying before age 70 years (70q0) and the mean age at death by cause and sex. This study enables comparisons of the impact of causes of death over time, offering a deeper understanding of how these causes affect global populations.

METHODS: GBD 2023 produced estimates for 292 causes of death disaggregated by age-sex-location-year in 204 countries and territories and 660 subnational locations for each year from 1990 until 2023. We used a modelling tool developed for GBD, the Cause of Death Ensemble model (CODEm), to estimate cause-specific death rates for most causes. We computed YLLs as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. Probability of death was calculated as the chance of dying from a given cause in a specific age period, for a specific population. Mean age at death was calculated by first assigning the midpoint age of each age group for every death, followed by computing the mean of all midpoint ages across all deaths attributed to a given cause. We used GBD death estimates to calculate the observed mean age at death and to model the expected mean age across causes, sexes, years, and locations. The expected mean age reflects the expected mean age at death for individuals within a population, based on global mortality rates and the population's age structure. Comparatively, the observed mean age represents the actual mean age at death, influenced by all factors unique to a location-specific population, including its age structure. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 250-draw distribution for each metric. Findings are reported as counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2023 include a correction for the misclassification of deaths due to COVID-19, updates to the method used to estimate COVID-19, and updates to the CODEm modelling framework. This analysis used 55 761 data sources, including vital registration and verbal autopsy data as well as data from surveys, censuses, surveillance systems, and cancer registries, among others. For GBD 2023, there were 312 new country-years of vital registration cause-of-death data, 3 country-years of surveillance data, 51 country-years of verbal autopsy data, and 144 country-years of other data types that were added to those used in previous GBD rounds.

FINDINGS: The initial years of the COVID-19 pandemic caused shifts in long-standing rankings of the leading causes of global deaths: it ranked as the number one age-standardised cause of death at Level 3 of the GBD cause classification hierarchy in 2021. By 2023, COVID-19 dropped to the 20th place among the leading global causes, returning the rankings of the leading two causes to those typical across the time series (ie, ischaemic heart disease and stroke). While ischaemic heart disease and stroke persist as leading causes of death, there has been progress in reducing their age-standardised mortality rates globally. Four other leading causes have also shown large declines in global age-standardised mortality rates across the study period: diarrhoeal diseases, tuberculosis, stomach cancer, and measles. Other causes of death showed disparate patterns between sexes, notably for deaths from conflict and terrorism in some locations. A large reduction in age-standardised rates of YLLs occurred for neonatal disorders. Despite this, neonatal disorders remained the leading cause of global YLLs over the period studied, except in 2021, when COVID-19 was temporarily the leading cause. Compared to 1990, there has been a considerable reduction in total YLLs in many vaccine-preventable diseases, most notably diphtheria, pertussis, tetanus, and measles. In addition, this study quantified the mean age at death for all-cause mortality and cause-specific mortality and found noticeable variation by sex and location. The global all-cause mean age at death increased from 46·8 years (95% UI 46·6-47·0) in 1990 to 63·4 years (63·1-63·7) in 2023. For males, mean age increased from 45·4 years (45·1-45·7) to 61·2 years (60·7-61·6), and for females it increased from 48·5 years (48·1-48·8) to 65·9 years (65·5-66·3), from 1990 to 2023. The highest all-cause mean age at death in 2023 was found in the high-income super-region, where the mean age for females reached 80·9 years (80·9-81·0) and for males 74·8 years (74·8-74·9). By comparison, the lowest all-cause mean age at death occurred in sub-Saharan Africa, where it was 38·0 years (37·5-38·4) for females and 35·6 years (35·2-35·9) for males in 2023. Lastly, our study found that all-cause 70q0 decreased across each GBD super-region and region from 2000 to 2023, although with large variability between them. For females, we found that 70q0 notably increased from drug use disorders and conflict and terrorism. Leading causes that increased 70q0 for males also included drug use disorders, as well as diabetes. In sub-Saharan Africa, there was an increase in 70q0 for many non-communicable diseases (NCDs). Additionally, the mean age at death from NCDs was lower than the expected mean age at death for this super-region. By comparison, there was an increase in 70q0 for drug use disorders in the high-income super-region, which also had an observed mean age at death lower than the expected value.

INTERPRETATION: We examined global mortality patterns over the past three decades, highlighting-with enhanced estimation methods-the impacts of major events such as the COVID-19 pandemic, in addition to broader trends such as increasing NCDs in low-income regions that reflect ongoing shifts in the global epidemiological transition. This study also delves into premature mortality patterns, exploring the interplay between age and causes of death and deepening our understanding of where targeted resources could be applied to further reduce preventable sources of mortality. We provide essential insights into global and regional health disparities, identifying locations in need of targeted interventions to address both communicable and non-communicable diseases. There is an ever-present need for strengthened health-care systems that are resilient to future pandemics and the shifting burden of disease, particularly among ageing populations in regions with high mortality rates. Robust estimates of causes of death are increasingly essential to inform health priorities and guide efforts toward achieving global health equity. The need for global collaboration to reduce preventable mortality is more important than ever, as shifting burdens of disease are affecting all nations, albeit at different paces and scales.

FUNDING: Gates Foundation.},
}

@article {pmid41091803,
year = {2025},
author = {Wiley, HS and Lopez, CF and Rodin, AS and Rockne, RC and Yankeelov, TE and Sauro, HM and Hassan, G and Prabhakaran, S and Demir, E and Hu, M and Fuxman Bass, J and Luddy, KA and Newman, H and Mochel, JP and Costello, JC and Xing, J and Afify, SM and Acar, A and Hayden Gephart, M and Feng, S and Banks, O and Banerjee, J and Clayton, A and Hill, DE and Sweis, RF and Umeh-Garcia, MC and Su, Y and Meyer, AS},
title = {A Roadmap for the Future of Systems Biology in Cancer Research.},
journal = {Cancer research},
volume = {},
number = {},
pages = {},
doi = {10.1158/0008-5472.CAN-25-0700},
pmid = {41091803},
issn = {1538-7445},
abstract = {Cancer systems biology seeks to understand how cancer arises as a system of interconnected molecules, cells, and tissues, with the goal of understanding, predicting, and controlling the disease. In the last decade, the field has rapidly grown as advances in experimental, computational, and analytical technologies have improved our ability to capture and recapitulate the complexities of cancer at multiple scales. However, the field's promise to understand how specific molecular changes give rise to altered cancer outcomes remains incompletely fulfilled. Fortunately, an opportunity exists to accelerate progress by better coordinating modeling and data-gathering efforts across the cancer systems biology community. This will create the foundation for building accurate, multiscale cancer models that can better predict and identify improved therapeutic interventions. Here, we outline some of the current challenges in cancer systems biology research, how they can be addressed, and actions that the community can take to accelerate progress in the field.},
}

@article {pmid41088800,
year = {2025},
author = {Fuhrman, J and Yun, J and Indorf, A},
title = {Practical considerations and emerging approaches for the management of vasomotor and sexual symptoms in breast cancer patients on endocrine therapies.},
journal = {Expert review of clinical pharmacology},
volume = {},
number = {},
pages = {},
doi = {10.1080/17512433.2025.2573780},
pmid = {41088800},
issn = {1751-2441},
abstract = {INTRODUCTION: Vasomotor symptoms (VMS) and decreased libido are common menopausal symptoms. Patients with breast cancer receiving endocrine therapy experience new or worsening menopausal symptoms. Pharmacologic therapy for VMS has been centered on selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors, gabapentin, and clonidine. These therapeutic options fall short in obtaining adequate symptom relief, illustrating a therapeutic gap in efficacious treatment modalities. There are no historical systemic treatment options for low libido.

AREAS COVERED: This review summarizes the current pharmacologic therapy for VMS, focusing on the practical considerations for use of the novel VMS (fezolinetant, elinzanetant) and libido agents (flibanserin, bremelanotide). Literature search was completed with PUBMED, Cochrane Library, and Web of Science. Fezolinetant is a novel neurokinin 3 receptor antagonist that has demonstrated clinical benefit in patients without a history of breast cancer. For libido management, flibanserin and bremelanotide act as serotonin/dopaminergic modulators and melanocortin receptor agonists, respectively.

EXPERT OPINION: These novel agents are eagerly awaited therapeutic options; however, clinical trials excluded breast cancer patients. This review provides clinicians with relevant considerations to assess when recommending these therapies for patients with breast cancer, while awaiting ongoing research to give additional insights for best tailoring therapy for this patient population.},
}

@article {pmid41087806,
year = {2025},
author = {Yi, JC and Lee, E and Duggan, C and Baker, KS and Blythe, N and Cole, AM and Cushing-Haugen, KL and Gutierrez, AI and Linden, H and Mendoza, JA and Ohlsen, TJD and Ortblad, KF and Schwartz, SM and Yung, R and Ceballos, R and Chow, EJ},
title = {Perspective of Hispanic Cancer Survivors on Survivorship Care Plans: A Qualitative Study.},
journal = {Journal of immigrant and minority health},
volume = {},
number = {},
pages = {},
pmid = {41087806},
issn = {1557-1920},
support = {75N91020C00005/NH/NIH HHS/United States ; HHSN261201800004I/NH/NIH HHS/United States ; R21 CA258105/NH/NIH HHS/United States ; R21 CA258105/NH/NIH HHS/United States ; },
abstract = {Explore Hispanic cancer survivors' thoughts about survivorship care plans (SCPs), lay health educator (LHE)-delivered survivorship information, and general survivorship care among Hispanic cancer survivors. A subset of N = 95 participants (≥ 18 years) enrolled in a randomized controlled trial (RCT; March 2023 to August 2023) assessing the feasibility of LHE-delivered survivorship information completed phone-based interviews in which semi-structured guides probed their views on SCPs, the LHE call, and survivorship more broadly. Twenty participants (21% of the total enrolled) completed interviews (11 in English, 9 in Spanish). Most participants were female (70%), half were born in the United States (50%), and the majority had breast cancer (55%); the remaining had colorectal (5%), lymphoma (15%), and prostate cancers (25%). The average time since cancer diagnosis was 3.1 years (SD 1.8). Participants reported few issues transitioning from oncology to primary care and perceived that this transition was supported by easily accessible medical records that also help delineate the care responsibilities of different providers. Most participants thought the SCPs were easy to understand and helped them manage their survivorship care with confidence. They also found information on nutrition and physical activity helpful. Participants liked the LHE call but did not necessarily think it assisted with care coordination. Hispanic cancer survivors reported that the SCPs were helpful and easy to understand but that benefits of a survivorship-focused LHE session were less clear. Additional research may help to determine how best to utilize SCPs and LHEs for these survivors and their providers. Clinical Trials Registration: clinicaltrials.gov NCT04081779.},
}

@article {pmid41087744,
year = {2025},
author = {Abu-Shmais, AA and Freeman, G and Creanga, A and Vukovich, MJ and Malla, T and Mantus, GE and Shimberg, GD and Gillespie, RA and Guerra Canedo, V and Dadonaite, B and Rodgers, MD and Chopde, AJ and Bardwil-Lugones, E and Bylund, T and Henry, AR and Roberts-Torres, J and Johnston, TS and Smith, S and Yang, ES and Cheng, C and Walker, EL and Ravichandran, M and Gordon, IJ and Dittakavi, TS and Reed, DS and Pierson, TC and Dropulic, L and Bloom, JD and Tsybovsky, Y and Boritz, EA and Douek, DC and Zhou, T and Kanekiyo, M and Andrews, SF},
title = {Cross-neutralizing and potent human monoclonal antibodies against historical and emerging H5Nx influenza viruses.},
journal = {Nature microbiology},
volume = {},
number = {},
pages = {},
pmid = {41087744},
issn = {2058-5276},
support = {R01 AI141707/AI/NIAID NIH HHS/United States ; 75N93021C00015/AI/NIAID NIH HHS/United States ; UC7AI180311//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; UC7AI180311//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; R01 AI141707/AI/NIAID NIH HHS/United States ; 75N93021C00015/AI/NIAID NIH HHS/United States ; },
abstract = {Highly pathogenic avian influenza H5Nx viruses are an emerging threat for global health, especially clade 2.3.4.4b H5N1 virus which causes panzootic infections. Here we describe the isolation and characterization of broadly cross-neutralizing monoclonal antibodies (mAbs) against diverse H5Nx viruses from individuals who received a monovalent H5N1 vaccine 15 years ago. By screening over 500 mAbs, we identified 5 mAbs that neutralized the majority of H5 clades including 2.3.4.4b and target three distinct conserved epitopes within the HA globular head. Cryo-electron microscopy structures of these mAbs in complex with HA, deep mutational scanning and neutralization escape studies define the sites of vulnerability of H5 HA. These mAbs mediated stronger prophylactic protection against clade 2.3.4.4b H5N1 infection in mice than the best-in-class mAb targeting the HA stem. Our study identified several highly potent broadly neutralizing H5 mAbs from humans that either alone or in combination provide a pragmatic pandemic preparedness option against the threat of panzootic H5N1 influenza.},
}

@article {pmid41087376,
year = {2025},
author = {Edge, R and Matthews, S and Ahani, B and Aksyuk, AA and Clegg, L and Perez, JL and Esser, MT and Chang, LJ and Hirsch, I and Villafana, T and Pura, J and Stepanov, O and Streicher, K and White, T and Cohen, TS and Follmann, D and Gilbert, PB and Seegobin, S},
title = {A SARS-CoV-2 variant‑adjusted threshold of protection model for monoclonal antibody pre-exposure prophylaxis against COVID-19.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {9101},
pmid = {41087376},
issn = {2041-1723},
support = {Not applicable//AstraZeneca/ ; },
mesh = {Humans ; *COVID-19/prevention & control/immunology/virology ; *SARS-CoV-2/immunology/genetics/drug effects ; *Pre-Exposure Prophylaxis/methods ; *Antibodies, Monoclonal/immunology/therapeutic use/administration & dosage ; *Antibodies, Viral/immunology/blood ; Antibodies, Neutralizing/immunology/blood ; COVID-19 Drug Treatment ; Female ; Male ; Middle Aged ; Proportional Hazards Models ; Antibodies, Monoclonal, Humanized ; },
abstract = {Clinical development of monoclonal antibodies (mAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is challenging due to rapid changes in the variant landscape. This study identified a threshold model for neutralising antibody (nAb) titres associated with clinically relevant protection against symptomatic COVID-19 for vulnerable populations. Using efficacy data from the phase 3 PROVENT pre-exposure prophylaxis trial of tixagevimab-cilgavimab (NCT04625725), individual nAb ID50 titres were predicted by dividing serum mAb concentration by prevalence-adjusted tixagevimab-cilgavimab potency (from in vitro IC50 values combined with viral surveillance data) and related to efficacy with a Cox model. The Threshold of Protection (ToP) Cox model was externally validated using data from the phase 3 SUPERNOVA trial (NCT05648110), which assessed sipavibart efficacy against symptomatic COVID-19 in immunocompromised participants. The PROVENT ToP model estimated the variant-specific observed efficacies from SUPERNOVA for 3 and 6 months post any dose with Lin's concordance of 0.86 and 0.75, respectively. This approach integrates predicted nAb ID50 titres against multiple SARS-CoV-2 variants into a ToP model that can be applied across different variants and could serve as a surrogate endpoint in immunobridging studies to expedite clinical evaluation and regulatory approval for mAbs targeting SARS-CoV-2.},
}

Humans
*COVID-19/prevention & control/immunology/virology
*SARS-CoV-2/immunology/genetics/drug effects
*Pre-Exposure Prophylaxis/methods
*Antibodies, Monoclonal/immunology/therapeutic use/administration & dosage
*Antibodies, Viral/immunology/blood
Antibodies, Neutralizing/immunology/blood
COVID-19 Drug Treatment
Female
Male
Middle Aged
Proportional Hazards Models
Antibodies, Monoclonal, Humanized

@article {pmid40763278,
year = {2025},
author = {Simonin, M and Boissel, N and Petit, A and Mullighan, CG and Hunger, SP and Loh, ML and Winter, SS and Macintyre, E and Teachey, DT and Baruchel, A and Asnafi, V},
title = {Prognostic impact of the PredicT-ALL classifier in the AALL0434 trial: a model combining NGS, MRD, and WBC at diagnosis.},
journal = {Blood advances},
volume = {9},
number = {20},
pages = {5323-5326},
doi = {10.1182/bloodadvances.2025017399},
pmid = {40763278},
issn = {2473-9537},
}

@article {pmid41085624,
year = {2026},
author = {Finton, KAK and Foote-McNabb, UN and Wilcox, EC and Jones, LA and Gafken, PR and Strong, RK},
title = {Artemis: Mass Spectrometry-Based Identification of MHC-Presented Peptides Across Alleles, Classes, and Species Using Soluble Single-Chain MHC Constructs.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2980},
number = {},
pages = {231-250},
pmid = {41085624},
issn = {1940-6029},
mesh = {Humans ; *Peptides/immunology/genetics ; Alleles ; *Mass Spectrometry/methods ; *Antigen Presentation/immunology ; Animals ; *Major Histocompatibility Complex ; },
abstract = {The current "gold standard" for the identification of MHC-restricted peptides is conventional immunoprecipitation/mass spectrometry (MS); however, this approach requires a relatively large amount of sample, complex purification procedures, and computational analyses to assign peptides to individual alleles. Here, we provide instructions for the expression, purification, and MS identification of MHC-presented peptides of human and non-human, classical and non-classical, class I and class II proteins using a readily expressible, soluble, and easily purifiable single-chain dimer construct. This procedure enables the identification of up to tens of thousands of allele-specific peptides per run for peptidomics, ligandomics, therapeutic targeting, and motif analyses. Also included are instructions for construct design, streamlined lentiviral transfection and transduction, and computational methods for high-throughput processing of MS results, yielding high confidence peptide lists, motifs, and multiple analytics.},
}

Humans
*Peptides/immunology/genetics
Alleles
*Mass Spectrometry/methods
*Antigen Presentation/immunology
Animals
*Major Histocompatibility Complex

@article {pmid41085561,
year = {2025},
author = {Fryer, E and Bishop, DT and Campbell, PT and Chan, AT and Le Marchand, L and Li, CI and Moreno, V and Gunter, MJ and Phipps, AI and Grant, RC and Schmit, SL and Martin, RM and Yarmolinsky, J and Haycock, P},
title = {Investigating the causal effect of potential therapeutic agents for colorectal cancer prevention: a Mendelian randomization analysis.},
journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1158/1055-9965.EPI-25-0875},
pmid = {41085561},
issn = {1538-7755},
abstract = {BACKGROUND: Conventional observational studies have identified several potential therapeutic agents that may lower risk of colorectal cancer development. However, these studies are susceptible to unmeasured and residual confounding and reverse causation, undermining robust causal inference.

METHODS: We used Mendelian randomization (MR), a genetic epidemiological method that can strengthen causal inference, to evaluate the effect of previously reported therapeutic agents on colorectal cancer risk, including medications, dietary micronutrients, and exogenous hormones. Genetic instruments were constructed using genome-wide association studies (GWASs) of molecular traits (e.g. circulating levels of protein drug targets, blood-based biomarkers of micronutrients, circulating levels of endogenous hormones). Using summary statistics from these GWASs and a colorectal cancer risk GWAS (cases=78,473, controls=107,143), we employed Wald ratios and inverse-variance weighted models to estimate causal effects.

RESULTS: We found evidence for associations of genetically-proxied elevated omega-3 fatty acids (OR 1.10; 95% CI 1.03, 1.18; p=6.20x10-3) and reduced plasma ACE levels (OR 1.08; 95% CI 1.03, 1.13; p=9.36x10-4) with colorectal cancer risk. Findings for ACE inhibition were consistent across sensitivity analyses.

CONCLUSIONS: Reduced plasma ACE levels were robustly linked to increased colorectal cancer risk. Further work is required to better understand the mechanism behind this finding and whether this translates to adverse effects via medication use (i.e. ACE inhibitors).

IMPACT: These findings provide updated evidence on the role of previously reported therapeutic agents in colorectal cancer risk, helping to prioritise further evaluation of those agents with potential aetiological roles in cancer development.},
}

@article {pmid41084890,
year = {2025},
author = {Fitzgerald, L and Ghosh, S and Bokun, A and Lax, A and Mu, F and Wu, E and Lin, Y and Shi, L and Qureshi, ZP and Graf, SA},
title = {Healthcare cost comparison between first-line ibrutinib and acalabrutinib in chronic lymphocytic leukemia patients in the Veterans Affairs.},
journal = {Journal of comparative effectiveness research},
volume = {},
number = {},
pages = {e250084},
doi = {10.57264/cer-2025-0084},
pmid = {41084890},
issn = {2042-6313},
abstract = {Aim: Bruton's tyrosine kinase inhibitors (BTKis), including ibrutinib and acalabrutinib, transformed the treatment landscape of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) by improving outcomes compared with chemoimmunotherapy. Real-world economic comparisons between BTKis are needed in diverse populations. This study aimed to compare healthcare costs in the Veterans Health Administration (VHA) among patients with CLL/SLL treated with, and remaining persistent on, first-line (1L) ibrutinib versus acalabrutinib monotherapy for 12 months. Materials & methods: This retrospective study used VHA electronic medical record data from January 2006 to July 2024. Eligible patients initiated 1L ibrutinib or acalabrutinib monotherapy on or after November 2019 and remained on continuous treatment for ≥12 months. All-cause and CLL/SLL-related costs were assessed over 12 months of follow-up. Generalized linear models were used to estimate adjusted costs and compare differences between treatment cohorts. Results: A total of 1059 patients were included (ibrutinib: n = 732; acalabrutinib: n = 327). During the 12-month follow-up of continuous 1L treatment, the annual adjusted all-cause total healthcare cost difference between ibrutinib and acalabrutinib was -$2422 (p = 0.46) (adjusted medical cost difference: $5259, p = 0.03; adjusted pharmacy cost difference: -$5886, p = 0.02). The annual adjusted CLL/SLL-related total healthcare cost difference between ibrutinib and acalabrutinib was -$3793 (p = 0.15) (adjusted medical cost difference: $2085, p = 0.05; adjusted pharmacy cost difference: -$5860, p = 0.02). Conclusion: Among VHA patients with CLL/SLL who initiated and remained on treatment with 1L BTKi monotherapy for 12 months, annual all-cause and CLL/SLL-related total healthcare costs were similar between ibrutinib and acalabrutinib. Pharmacy costs were lower for ibrutinib, while medical costs were lower for acalabrutinib, resulting in overall comparable total costs.},
}

@article {pmid41084727,
year = {2025},
author = {Özcan, M and Cassaday, RD and Zarzycka, E and Vandendries, E and Zhang, F and Chen, Y and Nieto, A and Demirkan, F and Montesinos, P and Altuntas, F},
title = {Comparing two different doses of inotuzumab ozogamicin treatment in adult patients with acute lymphoblastic leukemia: a plain language summary of publication.},
journal = {Therapeutic advances in medical oncology},
volume = {17},
number = {},
pages = {17588359251370948},
doi = {10.1177/17588359251370948},
pmid = {41084727},
issn = {1758-8340},
abstract = {What is this summary about? This summary describes the results of a clinical study that compared two different doses of a treatment, called inotuzumab ozogamicin (inotuzumab for short), for acute lymphoblastic leukemia (ALL for short). This summary describes the results for people aged 18 years and older who took part in the study. Why was this study done? People who took part in the study had a higher risk of developing a side effect called sinusoidal obstruction syndrome (SOS for short), also known as veno-occlusive disease (VOD for short), which is a rare condition where some of the small blood vessels in the liver become blocked. Researchers wanted to find out if receiving a lower dose than the recommended dose of inotuzumab reduced the likelihood of people developing SOS after a stem cell transplant. Researchers wanted to find out if a lower dose of inotuzumab would also impact the efficacy (how well inotuzumab works to treat ALL) in people with ALL and what other side effects occurred.},
}

@article {pmid41083679,
year = {2025},
author = {Salit, RB and Hexner, EO and Gagelmann, N and Kröger, N and McLornan, DP and Jain, T and Gupta, V and Hobbs, GS and Tamari, R and Robin, M and Scott, B and Saber, W},
title = {Defining remission following hematopoietic cell transplant for myelofibrosis: an international expert panel consensus.},
journal = {Leukemia},
volume = {},
number = {},
pages = {},
pmid = {41083679},
issn = {1476-5551},
}

@article {pmid41082548,
year = {2025},
author = {Matsuno, A and Tollefson, D and Cover, J and Obong'o, C and Gamba, H and Chen, YQ and Duerr, A},
title = {What drives adolescent girls and young women's decisions to persist on PrEP? Results of a comparative qualitative study from a DREAMS program in western Kenya.},
journal = {AIDS care},
volume = {},
number = {},
pages = {1-11},
doi = {10.1080/09540121.2025.2570098},
pmid = {41082548},
issn = {1360-0451},
abstract = {Oral pre-exposure prophylaxis (PrEP) is a valuable tool to help end HIV, but persistent PrEP use is low amongst adolescent girls and young women (AGYW) in sub-Saharan Africa (SSA), who are at high risk for HIV. To improve persistent PrEP use in AGYW, more research is needed to understand what drives their decisions to continue with PrEP. We conducted a thematic, comparative qualitative analysis of in-depth interviews with 32 AGYW who participated in PEPFAR's DREAMS program in western Kenya: 16 were randomly sampled among those who persisted with PrEP and 16 among those who discontinued. We compared results between these groups to explore drivers for the decision to persist with PrEP. We interpreted findings using the Integrated Behavior Model, which posits that the decision to persist is influenced by attitudes, social norms and personal agency. Three themes emerged that illuminated AGYW's decision to persist with PrEP. First, having positive attitudes towards PrEP was insufficient to ensure persistence in absence of correct knowledge. All AGYW were positive about PrEP, but those who discontinued often had insufficient/misinformation about PrEP, specifically on its appropriate use during pregnancy/breastfeeding. Second, support from family and friends was critical to overcome societal stigma and could counter lack of support from romantic partners. Third, strong mentors supported PrEP persistence by increasing self-agency, but this was secondary in importance to the need for robust knowledge and social support. To improve PrEP persistence amongst AGYW in SSA, PrEP programs may benefit from increasing education delivered to AGYWs and their communities, specifically family and friends. In particular, messages that PrEP may be used when pregnant/breastfeeding should be reinforced. Other health programs for AGYWs may also benefit from an increased focus on educational messaging to program recipients and people in their existing social networks.},
}

@article {pmid41081510,
year = {2025},
author = {Dadonaite, B and Harari, S and Larsen, BB and Kampman, L and Harteloo, A and Elias-Warren, A and Chu, HY and Bloom, JD},
title = {Spike mutations that affect the function and antigenicity of recent KP.3.1.1-like SARS-CoV-2 variants.},
journal = {Journal of virology},
volume = {},
number = {},
pages = {e0142325},
doi = {10.1128/jvi.01423-25},
pmid = {41081510},
issn = {1098-5514},
abstract = {SARS-CoV-2 is under strong evolutionary selection to acquire mutations in its spike protein that reduce neutralization by human polyclonal antibodies. Here, we use pseudovirus-based deep mutational scanning to measure how mutations to the spike from the recent KP.3.1.1 SARS-CoV-2 strain affect cell entry, binding to the ACE2 receptor, RBD up/down motion, and neutralization by human sera and clinically relevant antibodies. The spike mutations that most affect serum antibody neutralization sometimes differ between sera collected before versus after recent vaccination or infection, indicating that these exposures shift the neutralization immunodominance hierarchy. The sites where mutations cause the greatest reduction in neutralization by post-vaccination or infection sera include receptor-binding domain (RBD) sites 475, 478, and 487, all of which have mutated in recent SARS-CoV-2 variants. Multiple mutations outside the RBD affect sera neutralization as strongly as any RBD mutations by modulating the RBD up/down movement. Some sites that affect RBD up/down movement have mutated in recent SARS-CoV-2 variants. Finally, we measure how spike mutations affect neutralization by three clinically relevant SARS-CoV-2 antibodies: VYD222, BD55-1205, and SA55. Overall, these results illuminate the current constraints and pressures shaping SARS-CoV-2 evolution and can help with efforts to forecast possible future antigenic changes that may impact vaccines or clinical antibodies.IMPORTANCEThis study measures how mutations to the spike of a SARS-CoV-2 variant that circulated in early 2025 affect its function and recognition by both the polyclonal antibodies produced by the human immune system and monoclonal antibodies used as prophylactics. These measurements are made with a pseudovirus system that enables safe study of viral protein mutations using virions that can only infect cells once. The study identifies mutations that decrease recognition by current human antibody immunity; many of these mutations are increasingly being observed in new viral variants. It also shows the importance of mutations that move the spike's receptor-binding domain up or down. Overall, these results are useful for forecasting viral evolution and assessing which newly emerging variants have reduced recognition by immunity and antibody prophylactics.},
}

@article {pmid41081432,
year = {2025},
author = {Avanessian, SC and van den Bijgaart, RJE and Chew, NW and Supper, VM and Tang, TT and Zhang, Y and Zhao, YQ and Abe, K and Gauthier, J and Barry, KC},
title = {IL-2/IL-15 signaling induces NK cell production of FLT3LG augmenting anti-PD-1 immunotherapy.},
journal = {Cancer immunology research},
volume = {},
number = {},
pages = {},
doi = {10.1158/2326-6066.CIR-24-1259},
pmid = {41081432},
issn = {2326-6074},
abstract = {Natural killer (NK) cells play a critical role in anti-cancer immunity through their direct cytotoxicity and production of cytokines, such as Flt3L. NK cell production of Flt3L controls conventional type I dendritic cell (cDC1) abundance in the tumor and promotes protective immune responses. Here, we show that NK cell production of Flt3l in the tumor is regulated by activation, and that activation by IL-2 and IL-15 uniquely induced Flt3L expression in NK cells. In melanoma, IL-2 signaling in NK cells led to increased Flt3L production, which boosted cDC1 abundance in the tumor and improved anti-PD-1 immunotherapy response. Further, NK cell subsets differentially regulated Flt3L in the tumor, with CD11b-CD27+ NK cells in mouse tumors enriched for IL-2-family signaling and upregulated Flt3l upon activation. Consistently, human CD56brightCD16- NK cells more strongly correlated with cDC1 and FLT3LG expression than other NK cell subsets across multiple human melanoma datasets and cancer indications. This mechanistic study of NK cell regulation of FLT3LG and control of the NK cell-cDC1 axis provides insights and strategies for the development of more effective cancer immunotherapies.},
}

@article {pmid41077138,
year = {2025},
author = {Akaike, T and Thakuria, M and Silk, AW and Hippe, DS and Ch'en, PY and Park, SY and Urman, NM and Chiu, MW and Kim, H and Kim, EY and Hall, ET and Bhatia, S and Reddy, S and Krainock, M and Aleshin, A and Choi, JS and Tsai, K and Yom, SS and Yu, SS and Choi, J and Chandra, S and Nghiem, PT and Zaba, LC},
title = {Circulating tumor DNA level is associated with time to clinical recurrence in Merkel cell carcinoma: Implications for patient management.},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.10.032},
pmid = {41077138},
issn = {1097-6787},
abstract = {BACKGROUND: Merkel cell carcinoma (MCC) recurs in 40% of patients. Circulating tumor DNA (ctDNA) is an emerging blood-based biomarker for early MCC recurrence detection.

OBJECTIVE: To evaluate the timing and prognostic significance of ctDNA levels relative to clinical recurrence.

METHODS: This multicenter prospective study analyzed 669 tumor-informed ctDNA tests from 215 MCC patients (stage I-IV) without clinically evident disease after treatment.

RESULTS: Patients with at least one positive ctDNA test were more likely to experience recurrence compared to ctDNA-negative patients (hazard ratio: 18.1, 95% CI: 8.9-36.7), with 77% developing clinically evident disease by one year. The median interval between the first positive ctDNA and clinical recurrence was 2.7 months. Clinical recurrences usually occurred within 3 months for ctDNA levels above 10 molecules/mL, within 6 months for levels between 1-10 molecules/mL, and within 9 months for levels below 1 molecule/mL.

LIMITATIONS: In this real-world study, there was variability in timing and frequency of follow-up examinations, imaging, and ctDNA testing, although most patients were followed with both ctDNA and imaging.

CONCLUSIONS: A positive ctDNA test detects MCC recurrence approximately 3 months earlier than imaging. Negative ctDNA can help reduce imaging frequency through serial ctDNA monitoring, while positive ctDNA warrants closer patient follow-up.},
}

@article {pmid41076992,
year = {2025},
author = {Bouras, E and Yu, R and Kim, AE and Markozannes, G and Murphy, N and Albanes, D and Anderson, LN and Barry, EL and Berndt, SI and Bishop, DT and Brenner, H and Burnett-Hartman, A and Campbell, PT and Carreras-Torres, R and Chan, AT and Cheng, I and Devall, MA and Diez-Obrero, V and Dimou, N and Drew, DA and Gruber, SB and Gsur, A and Hoffmeister, M and Hsu, L and Huyghe, JR and Kawaguchi, E and Keku, TO and Kundaje, A and Küry, S and Le Marchand, L and Lewinger, JP and Li, L and Lynch, BM and Moreno, V and Morrison, JL and Newton, CC and Obón-Santacana, M and Palmer, JR and Papadimitriou, N and Pellatt, AJ and Peoples, AR and Pharoah, PDP and Platz, EA and Qu, C and Ruiz-Narvaez, E and Mendez, JS and Schoen, RE and Stern, MC and Thomas, CE and Tian, Y and Um, CY and Visvanathan, K and Vodicka, P and Vymetalkova, V and White, E and Wolk, A and Woods, MO and Wu, AH and Gunter, MJ and Gauderman, WJ and Peters, U and Evangelou, M and Tsilidis, KK},
title = {Using gene-environment interactions to explore pathways for colorectal cancer risk.},
journal = {EBioMedicine},
volume = {121},
number = {},
pages = {105964},
doi = {10.1016/j.ebiom.2025.105964},
pmid = {41076992},
issn = {2352-3964},
abstract = {BACKGROUND: Colorectal cancer (CRC) is a significant public health concern, highlighting the critical need for identifying novel intervention targets for its prevention.

METHODS: We conducted genome-wide interaction analyses for 15 exposures with established or putative CRC risk [body mass index (BMI), height, physical activity, smoking, type 2 diabetes, use of menopausal hormone therapy, non-steroidal anti-inflammatory drugs, and intake of alcohol, calcium, fibre, folate, fruits, processed meat, red meat, and vegetables], and used interaction estimates to explore pathways and genes underlying CRC risk. The adaptive combination of Bayes Factors (ADABF), and over-representation analysis (ORA) were used for pathway analyses, and findings were further investigated using publicly available resources [hallmarks of cancer, Open Targets Platform (OTP)].

FINDINGS: A total of 1973 pathways using ADABF, and 840 pathways using ORA, out of the 2950 analysed, were enriched (P < 0.05) for at least one exposure, as well as 1227 genes within the enriched pathways. Data were available for 811/1227 coding genes in the OTP, 241 of which were supported by strong relative abundance of prior evidence (overall OTP score > 0.05). Fifty percent of the genes (617/1227) mapped to at least one hallmark of cancer, most of which (388/617) pertained to the Sustaining Proliferative Signalling hallmark. Our findings reflect previously established pathways for CRC risk and highlight the emerging importance of several less studied genes. Common pathways were found for several combinations of exposures, potentially suggesting common underlying mechanisms.

INTERPRETATION: The results of the present analysis provide a basis for further functional research. If confirmed, they may help elucidate the etiological associations between risk factors and CRC risk and ultimately inform personalized prevention strategies.

FUNDING: This study was funded by Cancer Research UK (CRUK; grant number:PPRCPJT∖100005) and World Cancer Research Fund International (WCRF; IIG_FULL_2020_022). Funding for grant IIG_FULL_2020_022 was obtained from Wereld Kanker Onderzoek Fonds (WKOF) as part of the World Cancer Research Fund International grant programme. Full funding details for the individual consortia are provided in the acknowledgements.},
}

@article {pmid41076366,
year = {2025},
author = {Li, R and Hensley, PJ and Babjuk, M and Bukavina, L and Psutka, SP and Lerner, SP and O'Donnell, MA and Lotan, Y and Bree, KK and Redorta, JP and McConkey, DJ and Lee, BH and Mariappan, P and Mertens, LS and Soloway, MS and Svatek, RS and Tan, WS and Williams, SB and Gupta, S and Buckley, R and Kamat, AM},
title = {Intermediate-risk Non-muscle-invasive Bladder Cancer: Recommendations for Definitions, Risk Stratification, Management Strategies, and Clinical Trial Design from the International Bladder Cancer Group.},
journal = {European urology oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.euo.2025.08.003},
pmid = {41076366},
issn = {2588-9311},
abstract = {BACKGROUND AND OBJECTIVE: Intermediate-risk (IR) non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease, and standardized definitions and risk-guided management are critical for appropriate patient care and clinical trial development.

METHODS: A global committee of bladder cancer experts developed IR-NMIBC recommendations. Working groups reviewed literature and drafted recommendations, which were voted on by International Bladder Cancer Group (IBCG) members using a modified Delphi process. During an August 2024 meeting, voting results and evidence were presented, and recommendations were refined. Final recommendations achieved >75% agreement.

KEY FINDINGS AND LIMITATIONS: The IBCG recommends inclusion of only low-grade (LG; G1 and G2) tumors in the IR-NMIBC category, risk stratified using the IBCG IR-NMIBC risk scoring system. Given the relatively indolent course and treatment burden of IR-NMIBC, therapeutic deintensification with active surveillance or office-based ablation is appropriate for select patients. Morbidity related to transurethral resection of a bladder tumor can be mitigated by forgoing restaging resection in completely resected LG tumors and not mandating muscularis propria sampling. Perioperative chemotherapy reduces recurrences, and additional adjuvant intravesical treatment should be risk stratified. Clinical trials evaluating novel IR-NMIBC therapies, including adjuvant and ablative designs, should incorporate patient-reported outcomes and risk-stratified controls. Ablative trials, as proof-of-concept studies for efficacy, require randomized controlled studies in the adjuvant setting to confirm superiority over the standard of care.

The IBCG consensus recommendations provide practical guidance for clinical care and clinical trial design for patients with IR-NMIBC.},
}

@article {pmid41076116,
year = {2025},
author = {Louie, T and Snidarich, M and Hippe, DS and Wernli, KJ and Palazzo, L and Hansell, L and Brown, M and Coronado, GD and Lodhi, S and Leone, R and DeCell, K and Mardesich, K and Wysham, N and Triplette, M},
title = {A pragmatic pre-post intervention trial to address adherence to lung cancer screening follow-up in community settings (the ACCELL trial): Study protocol.},
journal = {Contemporary clinical trials},
volume = {},
number = {},
pages = {108106},
doi = {10.1016/j.cct.2025.108106},
pmid = {41076116},
issn = {1559-2030},
abstract = {BACKGROUND: Lung cancer remains the leading cause of cancer death in the United States. Annual lung cancer screening (LCS) with low-dose chest CT (LDCT) can prevent lung cancer deaths in high-risk individuals; However, these benefits are tempered by low adherence to annual screening and low rates of follow-up for those with abnormal findings.

OBJECTIVE: To evaluate the impact of centralized approaches to care coordination on LCS follow-up in community settings through a hybrid implementation-effectiveness trial.

METHODS: This is a pre-post intervention trial of a pragmatic and flexible approach to LCS care coordination delivered at the system-level at two community LCS programs based at regional hospitals in Washington state. Care coordination approaches include standardized LCS follow-up workflows incorporating universal tracking of LCS results, universal results delivery to patients, stepped approaches to follow-up reminders and personalized approaches to positive findings. Participants who are eligible for and undergo LCS during either period (n ~ 6750) will be included. Primary outcomes include adjusted changes in screening adherence to annual follow-up and follow-up for positive findings between the pre- (August 2022-January 2025) and post- (January 2025-July 2027) intervention period. Secondary outcomes include assessing the impact of interventions by community site, patient ethnicity, socioeconomic status, and rurality. We will also assess the implementation of the intervention with attention to adaptation, sustainability and equity.

DISCUSSION: Implementing centralizing care coordination models may decrease barriers and improve adherence to LCS in community settings and serve as a model to improve LCS follow-up in clinical care settings.

REGISTRATION: ClinicalTrials.gov ID NCT06324110.},
}

@article {pmid41075386,
year = {2025},
author = {Minnie, SA and Berrien-Elliott, MM and Smith, M and Biernacki, MA and Bleakley, M},
title = {Optimizing post-transplantation cell therapies to enhance graft-versus-leukemia effects in hematological malignancies.},
journal = {Current opinion in immunology},
volume = {97},
number = {},
pages = {102675},
doi = {10.1016/j.coi.2025.102675},
pmid = {41075386},
issn = {1879-0372},
abstract = {Allogeneic hematopoietic cell transplantation (HCT) can cure patients with high-risk hematologic malignancies. Donor T and natural killer (NK) cells contribute to graft-versus-leukemia (GVL) effects that provide relapse protection. Post-HCT relapses often represent inadequate GVL, but alloreactive lymphocytes that confer GVL may also cause graft-versus-host-disease (GVHD). Here, we review recent developments to selectively augment GVL while minimizing GVHD. Insights into the unique mechanisms of post-HCT T cell dysfunction highlight interventions to enhance GVL-mediating T cells. Early clinical data suggest that adoptive transfer of engineered donor T cells, expressing either transgenic T cell receptors specific for minor histocompatibility antigens presented exclusively on recipient hematopoietic cells or chimeric antigen receptors binding surface proteins on malignant cells, can mitigate post-HCT relapse. NK cells, key GVL mediators after haploidentical HCT, can be induced into a highly functional memory-like state and administered to HCT recipients to enhance GVL. These innovations promise much-needed improvements in post-HCT outcomes.},
}

@article {pmid41074700,
year = {2025},
author = {Aldoss, I and Ali, A and Cassaday, RD and Curran, EK and Luskin, MR and Maese, LD and Orgel, E and Douer, D},
title = {Optimizing Asparaginase Treatment for Adolescent and Young Adult (AYA) Patients With Acute Lymphoblastic Leukemia: US Consensus Panel Recommendations.},
journal = {American journal of hematology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ajh.70103},
pmid = {41074700},
issn = {1096-8652},
support = {//Jazz Pharmaceuticals/ ; },
abstract = {Asparaginase is an integral component of therapy for pediatric patients with acute lymphoblastic leukemia/lymphoblastic lymphoma. The success of asparaginase-containing regimens has led to trials of pediatric/pediatric-inspired regimens incorporating asparaginase for treating adolescent and young adult (AYA) and adult populations with acute lymphoblastic leukemia/lymphoblastic lymphoma. While treatment of AYA patients with these regimens is associated with improved clinical outcomes compared with adult-specific protocols, AYA patients face unique challenges with these treatments, further complicated by a rapidly evolving therapeutic landscape. In this article, we identify barriers and other feasibility issues associated with administering asparaginase-based treatment to AYA patients and provide recommendations from a consensus panel of experts to optimize AYA patient outcomes and experiences. Barriers identified include the limited access to clinical trials and specialized expertise in pediatric-inspired regimens for AYA patients compared with pediatric patients, the complex management of asparaginase toxicities, limited medical facilities and experienced staff to administer and manage pediatric-inspired regimens, and reduced AYA patient access/adherence to treatment due to lifestyle-related or psychosocial challenges. Recommendations are provided on addressing and managing these challenges to improve asparaginase-based treatment accessibility and safety in AYA patients, including specific recommendations for high-risk populations. Trial Registration: ClinicalTrials.gov: NCT04817761.},
}

@article {pmid41074685,
year = {2025},
author = {Banerjee, R and Kaur, G and Razzo, BM and Portuguese, AJ and Sidana, S and Richards, T and Grajales-Cruz, A and Richard, S and Shune, L and Khouri, J and Dima, D and Lee, HC and Patel, KK and Pasvolsky, O and Vazquez-Martinez, M and Hansen, DK and Afrough, A and Davis, JA and Hashmi, H and Atrash, S and Ferreri, CJ and Julian, KL and Herr, MM and Midha, S and Costello, P and Forsberg, P and de Menezes Silva Corraes, A and Lin, Y and Cowan, AJ and Anderson, LD and Garfall, AL},
title = {Predictors of Delayed Responses to Teclistamab in Multiple Myeloma After Initial Non-Response.},
journal = {American journal of hematology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ajh.70108},
pmid = {41074685},
issn = {1096-8652},
support = {//Leukemia and Lymphoma Society (Blood Cancer United)/ ; },
}

@article {pmid41073880,
year = {2025},
author = {Koufigar, S and Ford, E and He, Y and Olsen, S and Fagerstrom, JM},
title = {A case study on SSD to SAD linear acceleartor calibration transition.},
journal = {Journal of applied clinical medical physics},
volume = {26},
number = {10},
pages = {e70298},
pmid = {41073880},
issn = {1526-9914},
mesh = {Calibration/standards ; Humans ; *Radiotherapy Planning, Computer-Assisted/methods/standards ; *Particle Accelerators/instrumentation/standards ; Radiotherapy Dosage ; *Quality Assurance, Health Care/standards ; *Neoplasms/radiotherapy ; *Radiotherapy, Intensity-Modulated/methods ; Retrospective Studies ; *Phantoms, Imaging ; },
abstract = {PURPOSE: Modifying calibration conditions of linear accelerators is infrequent and potentially a high-risk procedure. This study outlines a systematic approach used to transition a linear accelerator's calibration condition in an active clinical environment from source-to-surface (SSD) to source-to-axis (SAD), while maintaining treatment accuracy and avoiding interruption of clinical operations.

METHODS: A satellite clinic within a university radiation oncology service operated an Elekta Versa HD linear accelerator with SSD calibration, while other system C-arm accelerators used SAD. With a single installation of the treatment planning system used across all sites, it was decided to convert the machine to SAD calibration. Representative plans with diverse delivery techniques were comprehensively evaluated in advance. Over a single weekend, beams were recommissioned in the treatment planning system (TPS), and output was adjusted per AAPM's TG-51 protocol. Monitor units (MUs) for on-treatment patients were scaled manually in the oncology information system, MOSAIQ. Quality assurance (QA) checks, as well as independent peer-reviewing of each field, were performed to ensure safety and quality for this high-risk procedure. A retrospective failure modes and effects analysis (FMEA) was subsequently conducted. To evaluate the clinical relevance and broader impact of this work, a targeted survey was conducted via the Wayne State MedPhysUSA LISTSERV.

RESULTS: As a result of the change in output calibration condition, field MU required scaling, ranging from 2.7% to 6.4%. Patient-specific QA measurements demonstrated consistent gamma pass rates, and both solid-water phantom and external audit results verified machine output accuracy within 2%. No patient treatments were interrupted during the process. The FMEA identified insufficient expertise and staffing as the highest-risk failure mode. Survey results indicated that 80% of respondents had never personally performed a calibration transition with patients on treatment, and the majority of respondents characterized the procedure as extremely rare and of higher risk than standard TG-51 annual QA.

CONCLUSIONS: The absolute output calibration condition was successfully transitioned from SSD to SAD without interruptions of patient treatments. Multiple verification steps were implemented to ensure quality and safety. This project contributed to improved standardization across multiple sites of practice.},
}

Calibration/standards
Humans
*Radiotherapy Planning, Computer-Assisted/methods/standards
*Particle Accelerators/instrumentation/standards
Radiotherapy Dosage
*Quality Assurance, Health Care/standards
*Neoplasms/radiotherapy
*Radiotherapy, Intensity-Modulated/methods
Retrospective Studies
*Phantoms, Imaging

@article {pmid41073857,
year = {2026},
author = {Cannon, V and Wright, JH and Yeung, CCS and Grady, WM and Yu, M},
title = {Multiplex Digital PCR Assay Targeting DNA Methylation for Early Detection of Cancer.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2969},
number = {},
pages = {29-42},
pmid = {41073857},
issn = {1940-6029},
mesh = {*DNA Methylation ; Humans ; *Multiplex Polymerase Chain Reaction/methods ; *Early Detection of Cancer/methods ; *Esophageal Neoplasms/genetics/diagnosis ; Biomarkers, Tumor/genetics ; *Adenocarcinoma/genetics/diagnosis ; },
abstract = {Digital PCR has been demonstrated to enable the precise nucleic acid absolute quantification across a wide range of applications. Historically, dPCR technology was limited to two channels for fluorescence detection. Recent advances in digital PCR have made it possible to multiplex and allow for simultaneous analysis of multiple targets within a PCR reaction. Here, we describe a multiplex dPCR assay for the detection and quantification of methylated DNA (also known as DNA-methylation-specific multiplex digital PCR, or DNA-methylation specific dPCR). We also demonstrate the application of this technology for the development of a candidate DNA methylation-based biomarker panel for the early detection of high-grade dysplasia and esophageal adenocarcinoma. Further, we discuss common technical challenges and troubleshooting for performing successful DNA-methylation-specific MS-dPCR assays.},
}

*DNA Methylation
Humans
*Multiplex Polymerase Chain Reaction/methods
*Early Detection of Cancer/methods
*Esophageal Neoplasms/genetics/diagnosis
Biomarkers, Tumor/genetics
*Adenocarcinoma/genetics/diagnosis

@article {pmid41072416,
year = {2025},
author = {Di Meo, F and Albano, F and Cesarano, A and Wang, Y and Kale, B and Shain, K and Silva, A and Kurihara, N and Tenshin, H and Jellyman, D and Song, X and Ghaffari, S and Mesa, H and Creelan, B and Freeman, C and Zhao, X and Meads, MB and Rodriguez, PC and Marino, S and Locke, F and Hwu, P and Roodman, D and Mansilla-Soto, J and Perna, F},
title = {Developing SEMA4A-directed CAR T cells to overcome low BCMA antigen density in multiple myeloma.},
journal = {Cancer cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ccell.2025.09.007},
pmid = {41072416},
issn = {1878-3686},
abstract = {Chimeric antigen receptor (CAR) T cell therapy targeting B cell maturation antigen (BCMA) for multiple myeloma (MM) is effective, but relapses associated with low-to-negative BCMA expression are common, indicating the need for additional targets. We quantitatively profile antigen density in a cohort of patients relapsed after BCMA CAR T therapy, showing high number of SEMA4A molecules/cell where BCMA density is low. SEMA4A deletion limits MM cell growth, migration, tissue infiltration, and osteoclast formation, while extending mouse survival. We generate monoclonal antibodies targeting SEMA4A-extracellular domain for CAR construction, screen engineered T cells for expansion, cytokine release, and cytotoxicity against MM cells. Lead constructs lack reactivity against normal non-hematopoietic tissues. SEMA4A CAR T cells show superior efficacy than BCMA CAR T cells eliminating patient-derived BCMA[low] tumors and MM cells progressing under suboptimal doses of BCMA CAR T cells. This study prepares for a phase 1 clinical trial with SEMA4A-directed CAR T cells for MM.},
}

@article {pmid41071904,
year = {2025},
author = {Malladi, SK and Jaiswal, D and Ying, B and Alsoussi, WB and Darling, TL and Dadonaite, B and Civljak, A and Horvath, SC and Zhou, JQ and Kim, W and Turner, JS and Schmitz, AJ and Han, F and Scheaffer, SM and Farnsworth, CW and Nachbagauer, R and Nestorova, B and Chalkias, S and Klebert, MK and Edwards, DK and Paris, R and Strnad, BS and Middleton, WD and O'Halloran, JA and Presti, RM and Bloom, JD and Boon, ACM and Diamond, MS and Bajic, G and Ellebedy, AH},
title = {Germinal center-mediated broadening of B cell responses to SARS-CoV-2 booster immunization.},
journal = {Science immunology},
volume = {10},
number = {112},
pages = {eadu4107},
doi = {10.1126/sciimmunol.adu4107},
pmid = {41071904},
issn = {2470-9468},
mesh = {*Germinal Center/immunology ; *SARS-CoV-2/immunology ; Humans ; Animals ; *B-Lymphocytes/immunology ; Immunization, Secondary ; *COVID-19/immunology/prevention & control ; Spike Glycoprotein, Coronavirus/immunology ; *COVID-19 Vaccines/immunology ; Antibodies, Viral/immunology ; Adult ; Antibodies, Neutralizing/immunology ; Cricetinae ; Antibodies, Monoclonal/immunology ; Male ; Female ; },
abstract = {Germinal centers (GCs) are key sites for antibody diversification and affinity maturation. SARS-CoV-2 messenger RNA (mRNA) vaccines elicit robust GC B cell responses in humans, but how these responses influence the breadth of immunity against viral variants remains unclear. We analyzed GC B cell responses in nine healthy adults after mRNA booster immunization. We show that 77.8% of the B cell clones in the GC expressed representative monoclonal antibodies (mAbs) recognizing the spike protein, with 37.8% of these targeting the receptor binding domain (RBD). One RBD-targeting mAb, mAb-52, neutralized all tested SARS-CoV-2 strains, including the recent XEC variant. mAb-52 used the IGHV3-66 public clonotype, protected hamsters challenged against the EG.5.1 variant, and targeted the class I/II RBD epitope, closely mimicking the binding footprint of ACE2. Its broad reactivity was driven by extensive somatic hypermutation, underscoring the critical role of GC reactions in shaping cross-variant B cell immunity after SARS-CoV-2 booster vaccination.},
}

*Germinal Center/immunology
*SARS-CoV-2/immunology
Humans
Animals
*B-Lymphocytes/immunology
Immunization, Secondary
*COVID-19/immunology/prevention & control
Spike Glycoprotein, Coronavirus/immunology
*COVID-19 Vaccines/immunology
Antibodies, Viral/immunology
Adult
Antibodies, Neutralizing/immunology
Cricetinae
Antibodies, Monoclonal/immunology
Male
Female

@article {pmid41071741,
year = {2025},
author = {Dionne, JA and Campbell, JD and Salim, J and Atmar, RL and Healy, CM and Posavad, CM and Flach, B and Brown, ER and Farley, MM and Stephens, DS},
title = {Baptism in a Pandemic: Infectious Diseases Clinical Research Consortium Network Design for Readiness and Response.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {81},
number = {Supplement_2},
pages = {S109-S116},
doi = {10.1093/cid/ciaf419},
pmid = {41071741},
issn = {1537-6591},
}

@article {pmid41071598,
year = {2025},
author = {Corvera, S and Rajan, A and Townsend, KL and Shamsi, F and Wu, J and Svensson, KJ and Zeltser, LM and Collins, S and Reis, T and Tseng, YH and Goodyear, LJ},
title = {Advances in Adipose Tissue Biology.},
journal = {Endocrine reviews},
volume = {},
number = {},
pages = {},
doi = {10.1210/endrev/bnaf032},
pmid = {41071598},
issn = {1945-7189},
abstract = {Adipose tissue has emerged as a central regulator of human physiology, with its dysfunction driving the global rise in obesity-associated diseases, such as type 2 diabetes, cardiovascular and liver diseases, and several cancers. Once thought to be inert, adipocytes are now recognized as dynamic, responsive cells essential for energy homeostasis and interorgan communication, including the brain. Distinct adipose depots support specialized functions across development, sex, and aging. Technologies like single-cell RNA sequencing are unraveling depot-specific mechanisms, with the potential of identifying new therapeutic targets. This review highlights major scientific advancements leading to our current appreciation of the pivotal role of adipose tissue in health and disease. Many key discoveries in this field have been catalyzed by National Institutes of Health funding, particularly through the National Institute of Diabetes, Digestive and Kidney Diseases, now celebrating its 75th anniversary.},
}

@article {pmid38978671,
year = {2025},
author = {Blechter, B and Wang, X and Dai, J and Karsonaki, C and Shi, J and Shiraishi, K and Choi, J and Matsuo, K and Chen, TY and Hung, RJ and Chen, K and Shu, XO and Kim, YT and Choudhury, PP and Williams, J and Landi, MT and Lin, D and Zheng, W and Yin, Z and Zhou, B and Wang, J and Seow, WJ and Song, L and Chang, IS and Hu, W and Chien, LH and Cai, Q and Hong, YC and Kim, HN and Wu, YL and Wong, MP and Richardson, BD and Li, S and Zhang, T and Breeze, C and Wang, Z and Bassig, BA and Kim, JH and Albanes, D and Wong, JY and Shin, MH and Chung, LP and Yang, Y and Zheng, H and Dai, H and Yatabe, Y and Zhang, XC and Kim, YC and Caporaso, NE and Chang, J and Man Ho, JC and Daigo, Y and Momozawa, Y and Kamatani, Y and Kobayashi, M and Okubo, K and Honda, T and Hosgood, HD and Kunitoh, H and Watanabe, SI and Miyagi, Y and Matsumoto, S and Horinouchi, H and Tsuboi, M and Hamamoto, R and Goto, K and Takahashi, A and Goto, A and Minamiya, Y and Hara, M and Nishida, Y and Takeuchi, K and Wakai, K and Matsuda, K and Murakami, Y and Shimizu, K and Suzuki, H and Saito, M and Ohtaki, Y and Tanaka, K and Wu, T and Wei, F and Machiela, MJ and Kim, YH and Oh, IJ and Fun Lee, VH and Chang, GC and Chen, KY and Su, WC and Chen, YM and Seow, A and Park, JY and Kweon, SS and Gao, YT and Liu, J and Schwartz, AG and Houlston, R and Gorlov, IP and Wu, X and Yang, P and Lam, S and Tardon, A and Chen, C and Bojesen, SE and Johansson, M and Risch, A and Bickeböller, H and Ji, BT and Wichmann, HE and Christiani, DC and Rennert, G and Arnold, SM and Brennan, P and McKay, J and Field, JK and Davies, MPA and Shete, SS and Le Marchand, L and Liu, G and Andrew, AS and Kiemeney, LA and Zienolddiny-Narui, S and Grankvist, K and Cox, A and Taylor, F and Yuan, JM and Lazarus, P and Schabath, MB and Aldrich, MC and Jeon, HS and Jiang, SS and Chen, CH and Hsiao, CF and Hu, Z and Burdett, L and Yeager, M and Hutchinson, A and Hicks, B and Liu, J and Berndt, SI and Wu, W and Wang, J and Li, Y and Choi, JE and Park, KH and Sung, SW and Kang, CH and Wang, WC and Xu, J and Guan, P and Tan, W and Yu, CJ and Yang, G and Loon Sihoe, AD and Choi, YY and Park, IK and Hung, HH and Vermeulen, RCH and Cheng, I and Wu, J and Tsai, FY and Chan, JKC and Li, J and Lin, HC and Liu, J and Song, B and Sawada, N and Yamaji, T and Wyatt, K and Ma, H and Zhu, M and Wang, Y and Qi, T and Li, X and Ren, Y and Chao, A and Iwasaki, M and Zhu, J and Wu, G and Chen, CY and Chen, CJ and Yang, PC and Stevens, VL and Fraumeni, JF and Lin, K and Walters, RG and Chen, Z and Chatterjee, N and Gorlova, OY and Amos, CI and Shen, H and Hsiung, CA and Chanock, SJ and Rothman, N and Kohno, T and Lan, Q and Zhang, H},
title = {Stratifying Lung Adenocarcinoma Risk with Multi-ancestry Polygenic Risk Scores in East Asian Never-Smokers.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {38978671},
abstract = {BACKGROUND: Lung adenocarcinoma (LUAD) in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve LUAD risk prediction.

METHODS: PRSs were developed using genome-wide association study summary statistics from East Asian (8,002 cases; 20,782 controls) and European (2,058 cases; 5,575 controls) populations. Single-ancestry models included PRS-25, PRS-CT, and LDpred2; multi-ancestry models included LDpred2+PRS-EUR128, PRS-CSx, and CT-SLEB. Performance was evaluated in independent East Asian data from the Female Lung Cancer Consortium (FLCCA) and externally validated in the Nanjing Lung Cancer Cohort (NJLCC). We assessed predictive accuracy via AUC, with 10-year and (age 30-80) absolute risks estimates.

RESULTS: The best multi-ancestry PRS, using East Asian and European data via CT-SLEB (clumping and thresholding, super learning, empirical Bayes), outperformed the best East Asian-only PRS (LDpred2; AUC=0.629, 95% CI:0.618,0.641), achieving an AUC of 0.640 (95% CI:0.629,0.653) and odds ratio of 1.71 (95% CI:1.61,1.82) per SD increase. NJLCC Validation confirmed robust performance (AUC =0.649, 95% CI: 0.623, 0.676). The top 20% PRS group had a 3.92-fold higher LUAD risk than the bottom 20%. Further, the top 5% PRS group reached a 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year LUAD risk at age 50 (0.42%) by age 41, nine years earlier.

CONCLUSIONS: Multi-ancestry PRS approaches enhance LUAD risk stratification in East Asian never-smokers, with consistent external validation, suggesting future clinical utility.},
}

@article {pmid41071311,
year = {2025},
author = {Carballo, EV and Gonzalez-Ericsson, P and Lehmann, BD and Taylor, BC and Wulfkuhle, JD and Ocampo, A and Gallagher, RI and Huang, DS and Maxey, C and Steele, JA and Kleinberg, K and Sun, X and Marshall, JL and Sanchez, V and Opalenik, SR and Petricoin, E and Rimel, BJ and Balko, JM and Penn, CA},
title = {The impact of JAK1 pathogenic variants and MHC-I expression on response to immune checkpoint inhibition in endometrial cancer.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {},
number = {},
pages = {},
doi = {10.1158/1078-0432.CCR-25-1442},
pmid = {41071311},
issn = {1557-3265},
abstract = {PURPOSE: Immune checkpoint inhibitors (ICI) have increasing application in endometrial cancer, underscoring the need for robust biomarkers for patient selection. JAK1 pathogenic variants (PV) have previously been implicated in immune evasion. Here, we identify biomarkers predictive of ICI response in endometrial cancer and the implications of JAK1 PV in this context.

EXPERIMENTAL DESIGN: This is a translational study of tumors from 84 endometrial cancer patients treated with ICI. High-throughput proteomic-based profiling was used to quantify 193 phospho-/protein expression levels, including key JAK/STAT signaling pathway components. Associations with clinical outcomes were assessed using multivariate regression analysis. The functional consequences of JAK1 PV were explored through in vitro signaling assays and analyses of TCGA database.

RESULTS: MHC-I expression correlated with improved progression-free survival (p = 0.035), validated in orthogonal approaches. Notably, a subset of patients harboring JAK1 PVs demonstrated exceptional survival on ICI. In TCGA cohort of microsatellite instability-high (MSI-H) and DNA polymerase epsilon (POLE)-mutated tumors, homozygous loss of JAK1 (JAK1Hom) trended toward decreased survival, whereas heterozygous loss of JAK1 (JAK1Het) was associated with significantly improved survival (p = 0.026), suggesting partial retention of antigen presentation pathways. Among our ICI-treated MSI-H tumor samples, NK cell marker NCAM1 was associated with improved survival (p=0.02).

CONCLUSIONS: These data support MHC-I as a potential predictive biomarker for ICI response in endometrial cancer. Additionally, we show that partial retention of JAK1 signaling in JAK1Het tumors is associated with improved survival, potentially attributable to enhanced NK cell activity in tumors with low MHC-I expression.},
}

@article {pmid41070684,
year = {2025},
author = {Lynch, RC and Cassaday, RD and Smith, SD and Cowan, AJ and Warren, EH and Shadman, MS and Till, BG and Ujjani, CS and Morris, K and Rasmussen, H and Voutsinas, J and Gopal, AK},
title = {Long-term follow-up of dose-dense brentuximab vedotin, ifosfamide, carboplatin and etoposide in second-line treatment of relapsed/refractory classical Hodgkin lymphoma.},
journal = {British journal of haematology},
volume = {207},
number = {4},
pages = {1599-1603},
doi = {10.1111/bjh.70052},
pmid = {41070684},
issn = {1365-2141},
support = {//Seagen/ ; P30 CA015704/CA/NCI NIH HHS/United States ; K24 CA184039/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Hodgkin Disease/drug therapy/mortality/therapy ; Brentuximab Vedotin/administration & dosage/adverse effects ; Etoposide/administration & dosage/adverse effects ; Carboplatin/administration & dosage/adverse effects ; Ifosfamide/administration & dosage/adverse effects ; Female ; Male ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects/administration & dosage ; Adult ; Middle Aged ; Follow-Up Studies ; Adolescent ; Aged ; Young Adult ; Recurrence ; Salvage Therapy ; },
abstract = {This study presents the 5-year outcomes of a phase 1/2 trial (NCT02227199) evaluating dose-dense brentuximab vedotin (BV) combined with ifosfamide, carboplatin and etoposide (ICE) as second-line therapy in patients with relapsed classic Hodgkin lymphoma (cHL). Forty-five patients received at least one dose of BV-ICE, with the intention to proceed to autologous stem cell transplantation (ASCT). At a median follow-up of over 5 years, the progression-free survival was 77% (95% CI, 66%-91%) and overall survival was 91% (95% CI, 82%-100%). Of 37 patients who underwent ASCT, five relapsed; two received subsequent allogeneic transplantation and remain alive. Among eight patients who did not proceed to ASCT, four remain in complete remission long-term. Second malignancies developed in five patients post-ASCT, including two localized skin cancers and three non-skin cancers. These findings highlight BV-ICE as a highly active salvage regimen for relapsed cHL, with durable remissions in a majority of patients. The regimen may be especially relevant in the modern era for patients who relapse after Programmed Cell Death Protein 1 (PD-1) inhibitor-based front-line therapy and require additional treatment prior to planned ASCT.},
}

Humans
*Hodgkin Disease/drug therapy/mortality/therapy
Brentuximab Vedotin/administration & dosage/adverse effects
Etoposide/administration & dosage/adverse effects
Carboplatin/administration & dosage/adverse effects
Ifosfamide/administration & dosage/adverse effects
Female
Male
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects/administration & dosage
Adult
Middle Aged
Follow-Up Studies
Adolescent
Aged
Young Adult
Recurrence
Salvage Therapy

@article {pmid41068949,
year = {2025},
author = {Cao, J and Ferguson, M and Sun, J and Shen, M and Small, R and Hippe, DS and Zhao, X and Zhang, D and Watase, H and Yuan, C and Gao, P and DeMarco, JK and Nicosia, RF and Wang, Y and Li, H and Li, Z and Wang, Y and Kohler, T and Hatsukami, T and Sui, B},
title = {Composition of carotid plaques differs between Chinese and US patients: a histology study.},
journal = {Chinese neurosurgical journal},
volume = {11},
number = {1},
pages = {23},
pmid = {41068949},
issn = {2057-4967},
support = {81361120402 and 62271061//National Natural Science Foundation of China/ ; R01 NS083503, R01 HL61851, R01-HL60213, RO1 HL073401, and R01 HL103609/NH/NIH HHS/United States ; L232130//Beijing Natural Science Foundation/ ; },
abstract = {BACKGROUND: The clinical manifestations of cerebrovascular disease are known to differ between the Chinese and United States (US) populations as do the plaque features on imaging.

OBJECTIVES: The aim of this study was to investigate and compare the histological features of excised carotid plaques from Chinese and US patients.

METHODS: Carotid endarterectomy specimens collected from two prospective studies were included. The entire plaque was serially sectioned (10-µm thickness) at 0.5-1 mm intervals. Hematoxylin and eosin staining and Mallory's trichrome staining were performed. The morphology and components of the plaques were measured and compared between the two groups.

RESULTS: A total of 1152 histological sections from 75 Chinese patients and 1843 sections from 111 US patients were analyzed. The Chinese group had significantly smaller minimum lumen diameters (median: 1.1 vs. 1.3 mm, p = 0.046) and a larger percent wall volume (median: 74% vs. 70%, p = 0.018) than the US group. After adjusting for confounding factors, carotid plaques in the Chinese population had larger lipid pools (β = 10.0%, 95% CI: 4.9 to 15.9%), more recent intraplaque hemorrhage (IPH; β = 8.4%, 95% CI: 4.5 to 12.7%), less late IPH (β = - 8.2%, 95% CI: - 11.3 to - 5.4), and fewer fibrous cap disruptions (45% vs. 67%, p = 0.061). Chinese plaques were more homogeneous and had a higher percentage of plaques with features of xanthomas than did US plaques (20% vs 2.7%, p < 0.001).

CONCLUSIONS: The histology of Chinese plaques differs significantly from that of U.S. plaques, suggesting substantial differences in the pathophysiology of atherosclerotic cerebrovascular disease between Chinese and North American populations, which indicates a need for a different management approach.},
}