@article {pmid42845279,
year = {2026},
author = {Varnum-Finney, B and Heck, AM and Srivatsan, SR and Dozono, S and Wellington, R and Chankhunthod, AB and Nourigat-McKay, C and Dignum, T and Trapnell, C and Hadland, B},
title = {Multiplexed single cell transcriptomics optimizes mesodermal patterning and hemogenic endothelial output from murine embryonic stem cells.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42845279},
issn = {2692-8205},
abstract = {BACKGROUND: Early patterning of mesodermal precursor populations is a key step of hematopoietic development in the embryo. To better understand this process, we employed sci-Plex, a high-throughput method of measuring multiplexed perturbations at the single-cell level, to evaluate the transcriptional response of mouse embryonic stem cells subjected to a gradient of two key morphogens in early mesoderm/hematopoietic development, Activin and BMP4.

RESULTS: sci-Plex revealed varying combinations of Activin and BMP4 temporally influenced mesoderm patterning in vitro and subsequent production of cell types reflecting their in vivo counterparts. We leveraged sci-Plex data to further optimize the generation of intraembryonic-like hemogenic endothelial cells that serve as the precursors of definitive hematopoietic lineages, including hematopoietic stem cells.

CONCLUSIONS: This study highlights the utility of sci-Plex to dissect how dose and temporal integration of interacting signal pathways determines cell fates and serves as a resource to analyze cell fate choices in early mesoderm patterning at single cell resolution.},
}

@article {pmid42845533,
year = {2026},
author = {Bussey-Sutton, CR and Gray, CN and Wu, BJ and Peterson, JJ and Burgos, SD and Mills, CA and Herring, LE and Browne, EP and Turner, AW and Margolis, DM and Emerman, M and Strahl, BD},
title = {RelB proximity proteomics and CRISPR screening define chromatin regulators of noncanonical NF-κB control of HIV latency and reactivation.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42845533},
issn = {2692-8205},
abstract = {Activation of the non-canonical NF-κB pathway via RelB/p52 signaling by SMAC mimetics such as AZD5582 is a promising strategy to induce HIV expression from latency, but the chromatin mechanisms linking RelB/p52 to proviral regulation remain poorly defined. Here, we combine RelB BioID proteomics, targeted HIV-CRISPR screening, and pharmacologic validation to identify ncNF-κB-associated regulators of HIV expression. RelB BioID revealed an extensive interaction network of chromatin and transcriptional regulators in basal and AZD5582-activated states. Basally associated RelB proteins included NSD2, SWI/SNF components, UHRF1, and DNMT1, while AZD5582-enriched proteins included p300, USP7, LSD1/KDM1A, NuRD components, SIN3A, and HBO1/KAT7. Functional screening using a custom guide RNA library targeting all BioID-identified factors identified regulators that promote HIV reactivation, including HBO1/KAT7, NSD2, and SIN3A, and regulators that restrict HIV expression, including p300, CHD4, and USP7. Because KAT7/HBO1 and p300 encode acetyltransferases with opposing screen phenotypes, we tested whether their catalytic activities contribute to HIV transcriptional regulation and found that, consistent with the CRISPR screen, KAT7/HBO1 inhibition reduced AZD5582-induced reactivation, whereas p300 inhibition enhanced it. Together, these data define a resource linking the RelB-associated chromatin landscape to HIV latency and reactivation.},
}

@article {pmid42880233,
year = {2026},
author = {Sohn, MH and Dubocanin, D and Vollger, MR and Kwon, Y and Minkina, A and Munson, KM and Hart, SFM and Ranchalis, JE and Parmalee, NL and Sedeño-Cortés, AE and Ou, J and Neph, SJ and Au, NYT and Bohaczuk, S and Carroll, B and Frazar, CD and Harvey, WT and Hoekzema, K and Huang, MF and Jacques, CN and Jensen, DM and Kolar, JT and Lee, R and Lin, J and Loy, K and Mack, T and Mao, Y and Mitchell, MW and Pham, MM and Scheinfeldt, LB and Smith, G and Ryke, E and Smith, JD and Sutherlin, L and Swanson, EG and Weiss, JM and , and Carvalho, CMB and Coorens, THH and Harris, K and Wei, CL and Eichler, EE and Altemose, N and Bennett, JT and Stergachis, AB},
title = {A telomere-to-telomere map of somatic mutation burden and functional impact in a cancer.},
journal = {Cell},
volume = {189},
number = {21},
pages = {6630-6647.e8},
doi = {10.1016/j.cell.2026.09.033},
pmid = {42880233},
issn = {1097-4172},
support = {DP5 OD029630/OD/NIH HHS/United States ; T32 GM007454/GM/NIGMS NIH HHS/United States ; U01 HG013744/HG/NHGRI NIH HHS/United States ; UM1 DA058220/DA/NIDA NIH HHS/United States ; },
mesh = {Humans ; *Telomere/genetics/metabolism ; *Mutation ; *Melanoma/genetics/pathology ; Epigenesis, Genetic ; Centromere/metabolism ; Telomerase/metabolism ; },
abstract = {Cancer genomes harbor extensive somatic genetic and epigenetic variation, yet large portions of the genome remain inaccessible to conventional reference-based analyses. Here, we demonstrate that pairing a near-telomere-to-telomere (near-T2T) diploid assembly of a donor with deep short- and long-read sequencing of their melanoma reveals that 16% of somatic variants localize to sequences absent from GRCh38, with satellite repeats acting as hotspots for UV-associated mutagenesis. Centromere kinetochore binding domains emerge as focal sites of chromosome arm aneuploidy breakpoints and somatic genetic variation, features we further demonstrate are also present in non-cancerous tissues. By contrast, extensive epigenetic remodeling of kinetochore binding domains appears specific to oncogenesis. Single-molecule telomere analyses reconstruct the cycle of telomere erosion and telomerase-mediated extension during tumor evolution, while haplotype-resolved chromatin maps reveal widespread somatic epimutations impacting regulatory elements. Together, these findings define previously inaccessible dimensions of somatic variation and establish a framework for telomere-to-telomere studies of human mosaicism.},
}

Humans
*Telomere/genetics/metabolism
*Mutation
*Melanoma/genetics/pathology
Epigenesis, Genetic
Centromere/metabolism
Telomerase/metabolism

@article {pmid42880546,
year = {2026},
author = {Iovino, L and Ma, N and Davis, C and Glockling, L and Basom, R and Milano, F and Gauthier, J and Ali, N and Gooley, T and Mielcarek, MB and Sandmaier, BM and Wu, QV and Sorror, ML},
title = {Comprehensive, simplified, and objective comorbidity assessment before allogeneic hematopoietic cell transplantation: a comparative cohort study.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2026.10.022},
pmid = {42880546},
issn = {2666-6367},
abstract = {BACKGROUND: Pretransplant comorbidity assessment informs risk stratification before allogeneic hematopoietic cell transplantation (allo-HCT), but the optimal balance among comprehensiveness, simplicity, and objectivity of the information captured under the available comorbidity indices (CI) remains uncertain.

OBJECTIVE(S): Here, we are comparing the performance of different CIs of assessing pre-HCT comorbidities and predicting outcomes.

STUDY DESIGN: We calculated the HCT-CI, the augmented HCT-CI (augHCT-CI), and the recently proposed simplified comorbidity index (SCI) based on a set of fewer comorbidities. We generated a fourth, objective HCT-CI (objHCT-CI), constructed from the measurable components of the augHCT-CI. We analyzed data from 3,473 consecutive single-center allo-HCT recipients transplanted from 2008-2022. We estimated the Harrell's C-index of the four CIs, their time-dependent ROC (Receiver Operating Characteristic) curve, and their ability of stratifying cumulative incidence of non-relapse mortality (NRM) and overall survival (OS).

RESULTS: All four indices significantly stratified NRM and OS (P<0.001). C-indices for NRM were 0.600 for HCT-CI, 0.632 for augHCT-CI, 0.628 for SCI, and 0.610 for objHCT-CI; corresponding C-indices for OS were 0.584, 0.612, 0.587, and 0.591. On the question on comprehensiveness versus simplicity, among 951 patients classified as SCI score 0, the augHCT-CI identified additional risk heterogeneity: 1-year NRM was 5.4%, 8.1%, and 10.9% for augHCT-CI scores 0, 1-2, and ≥3, respectively (Gray P=0.025), and OS differed significantly across these groups (P<0.0001).

CONCLUSION(S): Performance of all indices was comparable. SCI offers simplicity, but may lose prognostic granularity among patients classified as lowest risk. Future tools should improve reproducibility and automation without sacrificing clinically meaningful comorbidity information.},
}

@article {pmid42523218,
year = {2026},
author = {Bauer, MS and Kumar, S and Donald-Paladino, M and Li, D and Klupt, KA and Glögl, M and Escamilla, AMF and Schlichthaerle, T and Muratspahić, E and Wang, X and Schmiderer, L and Kenny, S and Coventry, B and Faezov, B and Chen, W and Shida, AF and Lee, GR and Hsia, Y and Kibler, RD and Elowitz, MB and Lietha, D and Nabet, B and Baker, D},
title = {De novo design of selective kinase modulators.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42523218},
issn = {2692-8205},
abstract = {Protein kinases are critical regulators of cellular signaling, but precise modulation of their activity remains challenging due to their high structural conservation. Here, we present de novo designed genetically encoded miniproteins capable of activating or inhibiting focal adhesion kinase (FAK) by directly targeting the kinase domain itself. Among 96 binders designed to stabilize distinct conformational states of FAK, 33 modulated kinase activity. Biochemical characterization of the four most potent modulators revealed that two designs inhibit FAK with low-nanomolar IC50 values while the remaining two potentiated FAK activity by more than two-fold. When expressed in cells, the modulators preserved the same inhibitory and activating effects observed in vitro, establishing that designed conformational binders can directly tune FAK signaling in living cells. Taking advantage of the high similarity between kinases, we redesigned the FAK inhibitors to inhibit Src kinase. Our approach establishes a versatile platform for selective and genetically encoded kinase control as a way to rewire cell signaling and as a starting point for the discovery of novel modulatory sites of kinases.},
}

@article {pmid42873797,
year = {2026},
author = {Saini, J and Wong, T and Schwarz, M and McClure, R and Shepherd, A and Zeng, J and Rengan, R},
title = {An operational key performance indicator framework and reference data from a multi-room pencil beam scanning proton therapy center.},
journal = {PloS one},
volume = {21},
number = {10},
pages = {e0360926},
pmid = {42873797},
issn = {1932-6203},
mesh = {Longitudinal Studies ; *Proton Therapy/standards ; Facility Design and Construction ; Health Facility Size ; Quality Improvement ; Workflow ; Humans ; Retrospective Studies ; *Quality Indicators, Health Care/standards/statistics & numerical data ; Radiotherapy Planning, Computer-Assisted ; Efficiency, Organizational/standards/statistics & numerical data ; Reference Values ; *Health Facilities ; *Health Facility Administration/standards/statistics & numerical data ; },
abstract = {PURPOSE: Multi-room proton therapy centers face unique operational challenges related to shared beam delivery systems, extended treatment hours, and high clinical complexity. This study presents a structured framework of key performance indicators (KPIs) and reports longitudinal single-institution operational reference data from a multi-room proton therapy center to support operational assessment and continuous quality improvement.

METHODS AND MATERIALS: Operational KPIs were retrospectively evaluated for calendar year 2024 at a three-room proton therapy center utilizing pencil beam scanning. KPIs were categorized into three areas: beam performance, treatment planning and pre-treatment workflow, and treatment room operations. Beam performance metrics included site- and room-specific uptime and beam pauses. Treatment planning metrics quantified CT simulation-to-patient scheduling timelines with attribution to physician, dosimetry, and physics components. Treatment room operations metrics included appointment variance, slot utilization, and waiting-for-beam (WFB) time. Data were collected automatically using a commercial analytics platform integrating radio-frequency identification tracking and oncology information system. Metrics were analyzed longitudinally and stratified by treatment room, disease site, and workflow component.

RESULTS: For calendar year 2024, aggregate site uptime was 95.3%, weighted according to clinical operating time across the three treatment rooms; individual room uptimes ranged from 91.8% to 97.2%. Beam pauses were frequent but brief, resulting in 2,238 minutes of cumulative lost treatment time across 2024, equivalent to approximately 0.5% of total clinical operating time. Annual mean treatment planning time was 8.5 business days, with physician-related activities contributing the greatest variability across disease sites. Monthly average appointment variance ranged from 5 to 11 minutes, with most treatments initiated within 10 minutes of scheduled time. Across 2024, slot utilization was stable, with 73% of fractions completed within scheduled slots. Mean overrun and underrun durations were modest, although P90 overrun durations exceeded 10 minutes throughout the year. Mean WFB times were low and consistent, ranging from 1.5 to 2.3 minutes.

CONCLUSIONS: This study presents a practical KPI framework and a single-institution operational reference data for multi-room proton therapy center. These metrics may support longitudinal monitoring, identification of workflow inefficiencies, data-driven decision-making, and future multi-institutional benchmarking efforts.},
}

Longitudinal Studies
*Proton Therapy/standards
Facility Design and Construction
Health Facility Size
Quality Improvement
Workflow
Humans
Retrospective Studies
*Quality Indicators, Health Care/standards/statistics & numerical data
Radiotherapy Planning, Computer-Assisted
Efficiency, Organizational/standards/statistics & numerical data
Reference Values
*Health Facilities
*Health Facility Administration/standards/statistics & numerical data

@article {pmid42875015,
year = {2026},
author = {Amaravadi, H and Prusynski, RA and Fishman, P and Phipps, AI and Leland, NE and Mroz, TM},
title = {Incentives for Access: Changes in Admissions and Care Delivery for Metastatic Cancer Patients in Medicare Skilled Nursing Facilities, After the Patient-Driven Payment Model.},
journal = {Journal of applied gerontology : the official journal of the Southern Gerontological Society},
volume = {},
number = {},
pages = {7334648261494384},
doi = {10.1177/07334648261494384},
pmid = {42875015},
issn = {1552-4523},
abstract = {BackgroundCancer patients experience suboptimal care in skilled nursing facilities (SNFs). Medicare's Patient-Driven Payment Model (PDPM) incentivized SNFs to admit complex patients, potentially promoting admissions without appropriate changes in care delivery.ObjectiveTo evaluate changes in SNF admissions, rehabilitation therapy volume, and chemotherapy/radiation around admission or discharge, following PDPM and COVID-19.MethodsAdjusted interrupted time series examining 1,125,782 hospital stays from metastatic cancer patients, using 100% Traditional Medicare claims (2018-2021).ResultsPDPM was associated with increased SNF admissions (0.47 pp/month; 95% CI: [0.17, 0.76]) and an immediate reduction in therapy volume (-24.95 minutes per day, 95% CI: [-26.40, -23.48]). Chemotherapy use remained low, but increased by 21% at PDPM implementation, without subsequent slope change (RR: 1.21; 95% CI: [1.01, 1.46]); radiation was unchanged. COVID-19 reversed admission gains. SNF admissions for metastatic cancer patients increased without sustained changes in cancer-relevant care delivery, warranting investigation of health outcomes and outcome-driven policy.},
}

@article {pmid42878338,
year = {2026},
author = {Houghton, AM},
title = {Analytical and technical advances collide to produce novel insights into the tumor immune microenvironment.},
journal = {American journal of respiratory and critical care medicine},
volume = {},
number = {},
pages = {},
doi = {10.1093/ajrccm/aamag447},
pmid = {42878338},
issn = {1535-4970},
}

@article {pmid42878707,
year = {2027},
author = {Lakkaraja, M and Schmitt, EG and Sood, AK and Chen, K and Modi, AJ and Verbsky, JW and Torgerson, T and Wahbeh, G and Petrovic, A and Baker, KS and Cooper, MA and Burroughs, LM},
title = {Hematopoietic cell transplantation using treosulfan-based conditioning for IL-10 receptor deficiency.},
journal = {Journal of human immunity},
volume = {3},
number = {1},
pages = {},
pmid = {42878707},
issn = {3065-8993},
support = {1K08AI182483/NH/NIH HHS/United States ; P30CA015704/NH/NIH HHS/United States ; //Children's Discovery Institute of Washington University's Center for Pediatric Immunology/ ; //St. Louis Children's Hospital/ ; //American Society of Hematology/ ; //Cancer and Blood Disorders Center/ ; /CA/NCI NIH HHS/United States ; },
abstract = {IL-10 receptor deficiency is a life-threatening inborn error of immunity associated with early-onset inflammatory bowel disease. Hematopoietic cell transplantation (HCT) using treosulfan-based conditioning resulted in excellent survival with full donor engraftment. Importantly, anakinra effectively served as a bridge to HCT.},
}

@article {pmid42879280,
year = {2026},
author = {Greene, JE and Ahmad, K and Henikoff, S},
title = {Histone H3K27 methylation states are sequentially catalyzed in cycling cells.},
journal = {Cell reports},
volume = {45},
number = {10},
pages = {118149},
doi = {10.1016/j.celrep.2026.118149},
pmid = {42879280},
issn = {2211-1247},
abstract = {Polycomb domains form at silenced genes and are marked by histone H3 lysine 27 tri-methylation, but it is unclear how this methylation is maintained following DNA replication in proliferating cells. Here, we use CUT&Tag chromatin profiling to track the dynamics of H3K27 methylation in human cells. We find that tri-methylation in Polycomb domains is maintained by stepwise methylation after DNA replication. Outside of Polycomb domains, thousands of transcriptionally inactive genes gain histone H3K27 di-methylation hours after DNA replication. Acute treatment with small-molecule inhibitors of the Polycomb repressive complex 2 (PRC2) histone methyltransferase slows H3K27 methylation during S-phase of the cell cycle and increases acetylation of the residue. This effect is most pronounced at Polycomb domains replicating in early S-phase, thereby suggesting that early replication and slow histone methylation confer plasticity to developmentally silenced genes. Together, our results explain how H3K27 modification patterns are faithfully duplicated in rapidly proliferating cells.},
}

@article {pmid42879732,
year = {2026},
author = {Vo, PT and Walter, RB and Gooley, TA and Hamlin, DK and Haaf, R and Wong, R and Matesan, M and Santos, EB and Dorman, E and Lewis, DH and Behnia, S and Emery, RC and Li, Y and Orozco, JJ and Vesselle, H and Wilbur, DS and Storb, R and Sandmaier, BM},
title = {First-In-Human Study of [211]At-CD45 Radioimmunotherapy With Nonmyeloablative Conditioning Hematopoietic Cell Transplantation for Adults With Hematologic Malignancies.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2600877},
doi = {10.1200/JCO-26-00877},
pmid = {42879732},
issn = {1527-7755},
abstract = {PURPOSE: Relapse is the dominant cause of failure after allogeneic hematopoietic cell transplantation (HCT) for aggressive hematologic malignancies. CD45-directed radioimmunotherapy (RIT) has been investigated to intensify conditioning and augment antitumor efficacy. After gaining clinical experience with β-emitting radionuclides, attention is now shifting toward α-emitters, such as astatine-211 ([211]At), for their more potent and precise radiation delivery with minimized toxicity to surrounding tissues.

PATIENTS AND METHODS: To our knowledge, in this first-in-human, two-stage dose-finding study, we administered a single infusion of [211]At-labeled anti-CD45 monoclonal antibody before nonmyeloablative conditioning with fludarabine/2-3 Gy total body irradiation and allografting from HLA-matched or single-allele-mismatched donors in 45 adults (38-74 years of age) at a high relapse risk from myeloid malignancies or acute leukemia.

RESULTS: Seventeen patients were treated in stage I with 85-591 μCi/kg of [211]At. The patient receiving 591 μCi/kg developed veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS), thereby establishing 500 μCi/kg as the protocol-defined maximum tolerated dose and prompting initiation of stage II at that dose in 28 patients. Infusion reactions were mild. [211]At-CD45 RIT did not delay hematopoietic recovery, impair donor chimerism, or increase graft-versus-host disease (GVHD) rates. In stage II, six patients (all receiving sirolimus as part of GVHD prophylaxis for unrelated donor HCT) experienced VOD/SOS. Among the 13 patients with circulating blasts at baseline, blasts cleared in 12 before initiation of fludarabine/total body irradiation, demonstrating immediate cytotoxic activity. Estimated 1-year relapse-free and overall survival were 42% (95% CI, 28%-56%) and 49% (34%-62%), respectively.

CONCLUSION: [211]At-CD45 RIT can be incorporated into nonmyeloablative conditioning, with liver toxicity defining activity limits. Evidence of antitumor efficacy supports phase II evaluation.},
}

@article {pmid42856697,
year = {2026},
author = {Yaseen, F and Hippe, DS and Cui, S and Fu, J and Wang, S and Deng, L and Ye, T and Kinahan, PE and Zeng, J and Gennari, JH and Bowen, SR},
title = {Uncertainty-Aware Multiscale Treatment Response Forecasting in Advanced Non-Small Cell Lung Cancer Using Residual-Variance Conformal Prediction.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {42856697},
support = {R01 CA204301/CA/NCI NIH HHS/United States ; R01 CA258997/CA/NCI NIH HHS/United States ; },
abstract = {Voxel-level prediction of treatment response from longitudinal Fluorodexoyglucose (FDG) positron emission tomography / computed tomography (PET/CT) can enable spatially adaptive dose planning in advanced non-small cell lung cancer (NSCLC), but point predictions alone lack the uncertainty quantification needed for safe clinical decision-making. Standard conformal prediction (CP) provides distribution-free coverage but yields spatially uniform intervals and assumes exchangeability-an assumption violated by intra-tumoral spatial correlation. We propose a multiscale CP framework built on a re-optimized VoxelForecast generalized least squares model that explicitly captures voxel-level covariance. Variogram sensitivity analysis identified the Stable model as significantly superior to previouly used Matérn family. The framework combines hierarchical nested leave-one-patient-out calibration, which restores exchangeability for valid voxel-level coverage, with residual-variance CP (VarCP), which learns a heteroscedastic, location-dependent scale to produce adaptive intervals while preserving finite-sample marginal coverage guarantees. On two prospective NSCLC trial cohorts-FLARE-RT (N=25 locally advanced, chemoradiotherapy; 11,100 voxels) and BRIGHT (N=19 metastatic, chemoimmunotherapy; 26,980 voxels)-multiscale feature integration reduced voxel-level prediction error by 35% and 31%, respectively. VarCP maintained nominal coverage while producing 7-18% (FLARE-RT) and 4-8% (BRIGHT) narrower voxel-level intervals than a hierarchically calibrated standard CP baseline (paired Wilcoxon signed-rank, significant at most miscoverage levels), with comparable lesion-level gains (7-18% and 6-10%) via median-based aggregation of voxel residuals. VarCP delivers tighter yet mathematically guaranteed spatial uncertainty maps, supporting both voxel-level dose-adjustment and whole-lesion treatment planning in advanced NSCLC.},
}

@article {pmid42859918,
year = {2026},
author = {Domingues, A and Spector, LG and Tettamanti, G and Feychting, M and Nikkilä, A and Auvinen, A and Alimam, W and Abuhamed, J and Scheuer, ME and Lupo, PJ and Heck, JE and Hansen, J and Mueller, BA and Nelson, H and MacLehose, R and Marcotte, E},
title = {Maternal smoking and risk of childhood cancer: a report from the Childhood Cancer and Leukemia International Consortium.},
journal = {International journal of epidemiology},
volume = {55},
number = {5},
pages = {},
pmid = {42859918},
issn = {1464-3685},
support = {R01 CA286051/CA/NCI NIH HHS/United States ; 5R01CA286051/CA/NCI NIH HHS/United States ; T32 CA099936/CA/NCI NIH HHS/United States ; T32 ES010957/ES/NIEHS NIH HHS/United States ; //T32 ES010957/ ; },
mesh = {Humans ; Female ; Pregnancy ; *Prenatal Exposure Delayed Effects/epidemiology ; *Smoking/epidemiology/adverse effects ; Case-Control Studies ; Child ; *Neoplasms/epidemiology ; Risk Factors ; Male ; Child, Preschool ; Logistic Models ; Infant ; United States/epidemiology ; Odds Ratio ; Sweden/epidemiology ; Adult ; Adolescent ; Infant, Newborn ; *Maternal Exposure ; Finland/epidemiology ; },
abstract = {BACKGROUND: Although tobacco is an established carcinogen and components of tobacco smoke may cross the placental membrane, past studies of maternal prenatal smoking and childhood cancer have resulted in mixed or null results. However, many studies have relied on case-control methods and may be susceptible to various biases. We aimed to elucidate the nature of the relationship between maternal prenatal smoking and childhood cancer through a multinational analysis of prospectively recorded record-linkage studies with probabilistic bias methods.

METHODS: Data for this analysis came from existing population-based case-control record-linkage studies in the Childhood Cancer and Leukemia International Consortium, with studies from the USA, Sweden, Finland, and Denmark, including more than 20 000 cases and 300 000 controls. We assessed the association between maternal prenatal smoking and childhood cancer using logistic regression. Additionally, we conducted probabilistic bias analysis to investigate the effect of exposure misclassification using sensitivities and specificities from biomarker-based validation studies.

RESULTS: Both before and after bias adjustment, maternal smoking was not found to be associated with most cancers investigated. Maternal prenatal smoking was inversely associated with paediatric melanoma [bias-adjusted odds ratio (OR) 0.68, 95% simulation interval (SI): 0.47-0.98] and skin carcinomas and other/unspecified carcinomas (bias-adjusted OR: 0.72, 95% SI: 0.52-0.96), and positively associated and unspecified malignant tumours (bias-adjusted OR: 1.50, 95% SI: 1.21-1.84).

CONCLUSIONS: This analysis supports previous findings that there is little evidence of an effect of maternal prenatal smoking on childhood cancer risk, with few potential exceptions. However, due to numerous other detrimental effects, public health efforts should continue to further reduce its prevalence.},
}

Humans
Female
Pregnancy
*Prenatal Exposure Delayed Effects/epidemiology
*Smoking/epidemiology/adverse effects
Case-Control Studies
Child
*Neoplasms/epidemiology
Risk Factors
Male
Child, Preschool
Logistic Models
Infant
United States/epidemiology
Odds Ratio
Sweden/epidemiology
Adult
Adolescent
Infant, Newborn
*Maternal Exposure
Finland/epidemiology

@article {pmid42860034,
year = {2026},
author = {Lo, E and Clein, A and Tam, M and Trimble, S and Hardin, M and Ramirez, A and Kaldjian, E and Yu, EY and Cheng, HH and Yezefski, TA and Hsieh, AC and Grivas, P and Montgomery, B and Nelson, PS and Schweizer, MT and Sabath, DE and Blinka, S},
title = {Circulating Tumor Cell Synaptophysin and Androgen Receptor Expression Reflect Prostate Cancer Phenotypes in Metastatic Disease.},
journal = {The Prostate},
volume = {},
number = {},
pages = {},
doi = {10.1002/pros.70267},
pmid = {42860034},
issn = {1097-0045},
support = {R37 CA230617/CA/NCI NIH HHS/United States ; R01 GM135362/GM/NIGMS NIH HHS/United States ; R01 CA276308/CA/NCI NIH HHS/United States ; P50CA097186/CA/NCI NIH HHS/United States ; R37CA268450/CA/NCI NIH HHS/United States ; P30CA015704/CA/NCI NIH HHS/United States ; T32CA009515/CA/NCI NIH HHS/United States ; P01CA163227/CA/NCI NIH HHS/United States ; P01CA298991/CA/NCI NIH HHS/United States ; R01CA266452/CA/NCI NIH HHS/United States ; //Prostate Cancer Foundation/ ; DBG-25-1373505-01-RMC//American Cancer Society/ ; //Seattle Translational Tumor Research/ ; //Nancy & Dick Bernheimer/ ; //Matthews Family/ ; //Thomas & Patricia Wright Memorial Funds/ ; //Larry & Virginia Gordon Endowed Chair in Prostate and Bladder Cancer Research/ ; PC230420//CDMRP/ ; W81XWH-17-2-0043//DOD/ ; },
abstract = {BACKGROUND: Chronic exposure to androgen receptor (AR)-targeted therapies can drive lineage plasticity, leading to treatment resistance and neuroendocrine prostate cancer (NEPC), characterized by loss of AR expression and acquisition of neuroendocrine (NE) markers including synaptophysin (SYP). We evaluated concordance between circulating tumor cell (CTC) AR and SYP expression patterns and evidence of NE differentiation defined by clinical, pathologic, and genomic features.

METHODS: CTCs from patients with metastatic castration-resistant prostate cancer (mCRPC) were analyzed using the RareCyte platform with quantitative immunofluorescence imaging for SYP and AR. In patients with ≥ 5 CTCs, associations of CTC phenotype with PSA at collection and overall survival (OS) were assessed using the Wilcoxon rank-sum test, Fisher's exact test, and Kaplan-Meier analysis. Patients were retrospectively classified as AR-positive adenocarcinoma or NE-differentiated based on clinical, pathologic, and genomic data.

RESULTS: The AR/SYP CTC assay was analytically validated using cell-line spike-in models, achieving > 90% accuracy for both biomarkers. Of 52 patients with mCRPC, 27 had ≥ 5 evaluable CTCs and were included in the primary CTC phenotype analyses. The NE-differentiated cohort had a higher fraction of SYP-positive CTCs (median 28.6% vs 0.0%, p = 0.0084), whereas the AR-positive adenocarcinoma cohort had a higher fraction of AR-positive CTCs (median 96.7% vs 0.0%, p = 0.0004). Classification based on high AR or SYP expression (≥ 80% of CTCs positive) significantly distinguished cohorts and was associated with tissue histology (p = 0.0048). PSA at CTC collection was lower in the NE-differentiated cohort (median 3.83 vs 486.89 ng/mL; 95% CI: -1016 to -190.9). OS did not significantly differ between groups.

CONCLUSION: SYP and AR CTC expression showed strong concordance with tissue histology and clinical features of NE differentiation and AR-positive adenocarcinoma. These findings support the feasibility of CTC immunophenotyping to characterize lineage-associated phenotypes including SYP-expressing NE differentiation in mCRPC. Prospective validation in larger cohorts with matched tissue biopsies is needed to define the clinical utility of this approach.},
}

@article {pmid42860046,
year = {2026},
author = {Mongiovi, JM and Prince, N and Pacheco, JA and Lin, N and Townsend, MK and Trabert, B and Wentzensen, N and Lasky-Su, JA and Eliassen, AH and Clish, CB and Tworoger, SS and Zeleznik, OA and Sasamoto, N},
title = {Plasma metabolomic profiles associated with breastfeeding history and subsequent ovarian cancer risk.},
journal = {JNCI cancer spectrum},
volume = {},
number = {},
pages = {},
doi = {10.1093/jncics/pkag108},
pmid = {42860046},
issn = {2515-5091},
abstract = {BACKGROUND: Breastfeeding reduces ovarian cancer risk, but the underlying biological mechanisms remain unclear.

METHODS: We examined the association between a previously reported metabolite-based breastfeeding score with incident epithelial ovarian cancer risk in case-control studies nested within the Nurses' Health Studies (NHS/NHSII, n = 436) and Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO, n = 300) using conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for each study and conducted a meta-analysis. We investigated 606 individual breastfeeding-metabolite associations among 9,904 mid-life parous women in NHS/NHSII and 663 one-year postpartum women in the Vitamin D Antenatal Asthma Reduction Trial (VDAART). Metabolites associated with breastfeeding at p ≤ 0.05 after multiple testing correction for number of effective tests (NEF) were then assessed for their associations with ovarian cancer. Metabolite set enrichment analysis using Normalized Enrichment Score (NES) identified metabolite classes associated with breastfeeding using false discovery rate (FDR) were used for multiple testing correction.

RESULTS: The highest quartile of metabolite-based breastfeeding score was inversely associated with ovarian cancer risk (meta-analyzed odds ratio [OR]=0.62, 95%CI=0.39-0.99). Of the 14 individual metabolites associated with breastfeeding in NHS/NHSII and also measured in VDAART, similar direction of associations was observed for 11 metabolites. Phosphatidylcholines (PCs; NES=1.94; FDR=0.004) and phosphatidylethanolamines (PEs; NES=1.82; FDR=0.01) were positively enriched with increased breastfeeding duration. Ten metabolites including PCs and PEs were positively associated with breastfeeding and inversely associated with ovarian cancer.

CONCLUSION(S): Our results suggest alterations of systemic metabolism, particularly among PC and PE pathways, provide insight into biological pathways underlying the inverse breastfeeding-ovarian cancer association.},
}

@article {pmid42862393,
year = {2026},
author = {Zhu, A and Schenk, JM and Gulati, R and Beatty, SJ and VanDoren, M and Lin, DW and Porter, MP and Morrissey, C and Dash, A and Gore, JL and Etzioni, R and Plymate, SR and Neuhouser, ML and Wright, JL},
title = {Impact of a dietary and exercise intervention on health-related quality of life of prostate cancer patients on active surveillance with overweight/obesity: a secondary analysis of a randomized controlled trial.},
journal = {Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer},
volume = {34},
number = {11},
pages = {},
pmid = {42862393},
issn = {1433-7339},
mesh = {Humans ; Male ; *Prostatic Neoplasms/therapy/psychology/complications ; *Quality of Life ; Middle Aged ; Aged ; *Overweight/therapy/complications ; *Obesity/therapy/complications ; Surveys and Questionnaires ; *Exercise ; Weight Loss ; *Watchful Waiting ; *Exercise Therapy/methods ; },
abstract = {PURPOSE: Quality of life (QOL) is important for men on active surveillance (AS) for prostate cancer (PCa). To improve QOL, interventions such as those focused on diet and exercise have been proposed. However, their effectiveness remains unclear, especially in individuals with overweight/obesity.

METHODS: We previously conducted and published a randomized controlled trial of a lifestyle intervention for PCa patients on AS with overweight/obesity. Men were randomized to as follows: (1) 6-month diet and exercise intervention with a 7% weight loss goal vs (2) provided US Dietary and Physical Activity Guidelines. Herein, we report the secondary QOL findings from the trial. QOL was assessed at baseline and conclusion of the intervention via four validated questionnaires. Linear regression and two-sided t-tests evaluated mean differences. Subset analyses of the questionnaires were performed using cut-points correlating with clinical assessments.

RESULTS: Between 2016 and 2020, 100 men completed the trial. The intervention group had a mean weight loss of 7.1% vs 1.8% in controls. Despite this, no significant difference was observed between groups in general QOL (EQ-5D-5L), urinary QOL (IPSS), PCa-related QOL (EPIC-26), or PCa specific anxiety (MAX-PC). However, exploratory subgroup analyses demonstrated that participants with poor "bowel function," low "sexual bother," and good "sexual function" had clinically significant improvements of 12 (95% CI 0.1-24.0), 22 (95% CI 4.2-39.0), and 19 points (95% CI 4.4-34.0) on the EPIC-26.

CONCLUSION: In this secondary analysis of a previously published randomized trial, a 6-month diet and exercise intervention did not improve overall QOL among men with overweight/obesity on AS for PCa. While diet and exercise interventions may not universally improve QOL in this population, they remain important for broader health benefits and may offer targeted value for certain patients.},
}

Humans
Male
*Prostatic Neoplasms/therapy/psychology/complications
*Quality of Life
Middle Aged
Aged
*Overweight/therapy/complications
*Obesity/therapy/complications
Surveys and Questionnaires
*Exercise
Weight Loss
*Watchful Waiting
*Exercise Therapy/methods

@article {pmid42862790,
year = {2026},
author = {Younes, S and Chinyengetere, F and Russell, V and Thakkar, D and Mason, EF and Juskevicius, R and Kovach, AE and Li, S and Yin, CC and O'Malley, DP and Koff, JL and Jaye, DL and Love, C and Shingleton, JR and Owusu, D and Batra, A and Biral, LPA and Thacker, E and Parker, C and Happ, L and Chapman Fredricks, J and Lossos, IS and Ondrejka, SL and Hsi, E and Tse, E and Au-Yeung, RKH and Bhagat, G and Leeman-Neill, RJ and Chadburn, A and Czader, M and Fedoriw, Y and Naresh, KN and Dave, SS and Natkunam, Y},
title = {Elucidating the Gene Expression Signature of Rosai-Dorfman Disease: A Study from the Atlas of Blood Cancer Genomes Initiative.},
journal = {Cancer research communications},
volume = {},
number = {},
pages = {},
doi = {10.1158/2767-9764.CRC-25-0834},
pmid = {42862790},
issn = {2767-9764},
abstract = {Rosai-Dorfman disease (RDD) is a rare histiocytic disorder characterized by accumulation of large histiocytes in nodal and/or extranodal sites. The underlying biology of RDD and factors that distinguish it from the other histiocyte disorders are poorly understood. To better understand the disease biology, we employed whole transcriptome RNA sequencing to study the gene expression profiles of RDD as part of the Atlas of Blood Cancer Genomes (ABCG) initiative. Gene expression profiles of RDD (N=23) were then compared to two other histiocytoses (Langerhans cell histiocytosis (LCH, N=15) and Erdheim-Chester disease (ECD, N=4), which are most often considered in the clinicopathologic differential diagnosis of RDD. We found that gene expression levels by RNA sequencing correlated well with known immunohistochemistry results for diagnostic markers for all three diseases, highlighting the ability to use RNA-based approaches for diagnosis of these tumors. RDD samples showed enrichment of gene sets related to B cells and the IL27 pathway. In contrast, LCH showed enrichment of gene sets related to resting dendritic cells and the HNF3A pathway. We found significant differences in the composition of the microenvironment with an enrichment of memory B cells, plasma cells and CD8 T cells in the RDD microenvironment and enrichment of dendritic cells in the LCH microenvironment. In summary, our study demonstrates unique gene expression signatures in RDD that show overlap as well as distinctive patterns from LCH or ECD. These novel gene expression signatures encompass pathways that could potentially contribute to the pathogenesis and targeted treatment of this rare histiocytic entity.},
}

@article {pmid42868246,
year = {2026},
author = {Kalyan, A and Bradford, MC and Dubnicka, A and Terrones, I and Yao, K and Runco, DV and Pihoker, C and Baker, KS and Ronsley, R},
title = {Body Composition Assessment and Correlation to Metabolic Profile in Survivors of Childhood Brain Tumors.},
journal = {Journal of pediatric hematology/oncology},
volume = {},
number = {},
pages = {},
doi = {10.1097/MPH.0000000000003300},
pmid = {42868246},
issn = {1536-3678},
abstract = {INTRODUCTION: Survivors of childhood brain tumors (CBT) are at increased risk for metabolic syndrome, contributing to long-term cardiometabolic morbidity. BMI may underestimate risk by failing to capture altered body composition in this population. More precise tools such as air displacement plethysmography (ADP) may improve early risk detection. This study aimed to identify ADP-derived markers of adiposity and characterize early metabolic abnormalities at the end of cancer therapy.

METHODS: This was a prospective, single-visit study enrolling pediatric survivors of high-grade CBT aged 2 to 21 years, off therapy for <5 years. Data included anthropometric measurements, metabolic markers (glucose, insulin, lipids, adiponectin, leptin, IL-6), and body composition (fat mass, fat-free mass, percent fat, measured by ADP). Descriptive statistics were used to summarize demographics and clinical characteristics, and categorical variables were presented as counts and percentages. Pearson correlation coefficients were calculated for log adiponectin versus percent body fat and BMI z-score.

RESULTS: Thirty survivors of CBT (n=30; age: 6 to 23 y) were evaluated a median of 0.3 years after treatment. Over half were normal weight (53%), and 47% were overweight or obese; 20% had hypertension and 23% had elevated waist circumference. Body composition (n=29) showed high adiposity, with a mean fat mass of 33% and 59% having elevated fat percentage. Metabolic assessment demonstrated early cardiometabolic dysfunction: insulin resistance and significant insulin resistance by HOMA-IR were seen in 50% and 33%, respectively, and lipid abnormalities and the metabolic syndrome were seen in 27% and 15%, respectively. Higher adiposity was associated with worse metabolic health, with greater fat mass percentage in insulin-resistant patients (P<0.01) and higher BMI z-score (P=0.02). Adiponectin was inversely correlated with fat mass% (r=-0.72), but not with BMI z-score.

CONCLUSION: Childhood brain tumor survivors demonstrated a high prevalence of metabolic abnormalities and excess adiposity shortly after therapy completion. BMI underestimated abnormal adiposity compared with ADP-derived body composition assessment, supporting the need for comprehensive metabolic screening and early intervention during survivorship.},
}

@article {pmid42868995,
year = {2026},
author = {Newell, EW},
title = {The narrow path to CD8[+] T cell recognition of mutant p53.},
journal = {Immunity},
volume = {59},
number = {10},
pages = {2617-2619},
doi = {10.1016/j.immuni.2026.09.020},
pmid = {42868995},
issn = {1097-4180},
mesh = {Humans ; *Tumor Suppressor Protein p53/genetics/immunology ; *CD8-Positive T-Lymphocytes/immunology ; Mutation ; Animals ; *Neoplasms/immunology/genetics/therapy ; Antigen Presentation/immunology ; Antigens, Neoplasm/immunology ; Immunotherapy ; },
abstract = {Shared cancer driver mutations offer attractive targets for cancer immunotherapy, but their expression does not necessarily put them within the reach of a T cell response. In this issue of Immunity, Haratani et al. identify distinct barriers to the processing, presentation, and recognition of neoantigens generated from mutant p53 that help explain this gap.},
}

Humans
*Tumor Suppressor Protein p53/genetics/immunology
*CD8-Positive T-Lymphocytes/immunology
Mutation
Animals
*Neoplasms/immunology/genetics/therapy
Antigen Presentation/immunology
Antigens, Neoplasm/immunology
Immunotherapy

@article {pmid42870635,
year = {2026},
author = {Nixon, AB and Enserro, DM and Bender, DP and Liu, Y and Starr, MD and Brady, JC and Gonzalez Bosquet, J and Rimel, BJ and Holman, LL and Rivard, C and Veljovich, DS and Fehniger, J and Moroney, JW and Backes, FJ and Cadungog, M and Powell, MA and Castellano, T and Secord, AA and MacKay, HJ},
title = {Blood-based biomarkers in patients with recurrent, persistent, or metastatic endometrial cancer treated with olaparib and cediranib: Results from NRG-GY012.},
journal = {Cancer},
volume = {132},
number = {20},
pages = {e70649},
doi = {10.1002/cncr.70649},
pmid = {42870635},
issn = {1097-0142},
support = {1U10 CA180822//BIQSFP Funding and National Cancer Institute/ ; U10CA180868//BIQSFP Funding and National Cancer Institute/ ; },
mesh = {Humans ; Female ; Phthalazines/administration & dosage ; *Endometrial Neoplasms/drug therapy/blood/pathology/mortality ; *Biomarkers, Tumor/blood ; Indoles ; Piperazines/administration & dosage ; Quinazolines/administration & dosage ; *Neoplasm Recurrence, Local/drug therapy/blood/pathology ; Prognosis ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Interleukin-6/blood ; Middle Aged ; Aged ; Progression-Free Survival ; },
abstract = {BACKGROUND: The NRG-GY012 phase 2 trial evaluated olaparib, cediranib, and the combination in 120 patients with recurrent, persistent, or metastatic endometrial cancer (EC). Predictive and prognostic associations between blood-based biomarkers and clinical outcomes were assessed.

METHODS: Plasma samples collected at baseline, cycle 4 day 1, and disease progression were analyzed for circulating protein biomarkers (Angiome). The primary analysis evaluated the predictive impact of IL-6 on progression-free survival (PFS) and overall survival (OS). The predictive and prognostic impact of all other markers on PFS and OS were also evaluated.

RESULTS: Ninety-six baseline plasma samples were included in this analysis. Results from GOG-218 identified IL-6 was predictive of clinical benefit using a threshold of 2.9 pg/mL. Although the 2.9 pg/mL cut point did not validate in GY012, IL-6 associated with OS using the median level of 4.2 pg/mL as the cut point. Although patients with >4.2 pg/mL IL-6 had worse prognosis, higher IL-6 levels were associated with longer OS benefit in the cediranib arms (pintx = .085). In secondary analyses, osteopontin (OPN) and placental growth factor (PlGF) potentially predicted benefit. Patients with higher OPN levels had shorter OS in the olaparib arm, whereas patients with lower OPN had longer OS in the cediranib arms (pintx = .035). Patients with higher PlGF benefited more from cediranib (PFS, pintx = .030; OS, pintx = .024). Multiple prognostic markers were also identified.

CONCLUSIONS: IL-6 may be predictive of outcome; OPN and PlGF represent novel potential predictive biomarkers, in EC patients receiving anti-angiogenic therapy. Further evaluation is warranted.},
}

Humans
Female
Phthalazines/administration & dosage
*Endometrial Neoplasms/drug therapy/blood/pathology/mortality
*Biomarkers, Tumor/blood
Indoles
Piperazines/administration & dosage
Quinazolines/administration & dosage
*Neoplasm Recurrence, Local/drug therapy/blood/pathology
Prognosis
*Antineoplastic Combined Chemotherapy Protocols/therapeutic use
*Interleukin-6/blood
Middle Aged
Aged
Progression-Free Survival

@article {pmid42871344,
year = {2026},
author = {Bulstra, CA and Dai, X and Ngure, K and Rosenberg, MS and Wamuti, BM and Hontelez, JAC and Salomon, JA and Ortblad, KF and Bärnighausen, T},
title = {The impact of male circumcision on risk of HIV infection in sub-Saharan Africa: a household fixed-effects analysis of 279,351 men from 29 countries.},
journal = {Frontiers in public health},
volume = {14},
number = {},
pages = {1810573},
pmid = {42871344},
issn = {2296-2565},
support = {K99 MH121166/MH/NIMH NIH HHS/United States ; R00 MH121166/MH/NIMH NIH HHS/United States ; },
mesh = {Humans ; *Circumcision, Male/statistics & numerical data ; Male ; *HIV Infections/epidemiology/prevention & control ; Africa South of the Sahara/epidemiology ; Cross-Sectional Studies ; Adult ; Adolescent ; Young Adult ; Middle Aged ; Health Surveys ; Family Characteristics ; Risk Factors ; },
abstract = {INTRODUCTION: While voluntary medical male circumcision (VMMC) reduces the individual-level risk of HIV acquisition by approximately 60% in randomised-controlled trials, little is known about the 'real-world' long-term effect of medical and traditional male circumcision on the cumulative risk of HIV infection. We estimate the association between these for the first time using a quasi-experimental study design-a household fixed-effects analysis-for sub-Saharan Africa, the global region with the largest HIV burden.

METHODS: We pooled individual-level cross-sectional data from the nationally-representative Demographic and Health Surveys and AIDS Indicator Surveys across all sub-Saharan African countries in which the surveys included data on both male circumcision and HIV status. We estimated the association between male circumcision and HIV status using modified Poisson regression models with household fixed-effects-which control for unobserved and observed confounding shared by men living in the same household-and included additional individual-level controls for demographic characteristics, socio-economic factors, and sexual behaviour.

RESULTS: We included individual data from 279,351 male participants in 48 nationally-representative surveys conducted in 29 countries between 2003 and 2018. The mean survey-level prevalence of male circumcision was 65.9% (median 84.5%, IQR 28.8-68.1%) and HIV was 5.6% (median 2.5%, IQR 1.2-10.2%). We estimated that male circumcision was associated with a significant nearly one-fifth reduction in the cumulative risk of HIV infection (adjusted risk ratio 0.81, 95% CI 0.73-0.89).

CONCLUSION: Male circumcision was associated with a significant reduction in the risk of HIV infection in sub-Saharan Africa over the past two decades. Increased political and financial commitment to VMMC could likely lead to further reductions in HIV prevalence, especially when rolled out as a HIV prevention option in combination with other interventions.},
}

Humans
*Circumcision, Male/statistics & numerical data
Male
*HIV Infections/epidemiology/prevention & control
Africa South of the Sahara/epidemiology
Cross-Sectional Studies
Adult
Adolescent
Young Adult
Middle Aged
Health Surveys
Family Characteristics
Risk Factors

@article {pmid42872245,
year = {2026},
author = {Gupta, H and Allison, MA and Mossavar-Rahmani, Y and Perreira, KM and Gallo, LC and Oelsner, EC and Evenson, KR and Daviglus, M and Garcia-Bedoya, O and Sotres-Alvarez, D and Isasi, CR and Kaplan, R and Matsushita, K and Schrack, JA and Martinez-Amezcua, P},
title = {Association of psychological and financial distress with physical activity among Hispanic/Latino populations during the COVID-19 lockdowns in the United States.},
journal = {Journal of health equity},
volume = {3},
number = {1},
pages = {2712532},
pmid = {42872245},
issn = {2994-4694},
support = {R01 HL146132/HL/NHLBI NIH HHS/United States ; N01 HC065233/HL/NHLBI NIH HHS/United States ; N01 HC065236/HL/NHLBI NIH HHS/United States ; N01 HC065235/HL/NHLBI NIH HHS/United States ; N01 HC065234/HL/NHLBI NIH HHS/United States ; N01 HC065237/HL/NHLBI NIH HHS/United States ; OT2 HL156812/HL/NHLBI NIH HHS/United States ; },
abstract = {We examined the links between COVID-19-related concerns, psychological distress, material hardship, and physical activity (PA) among Hispanic/Latino adults in the U.S. during the pandemic. We conducted a cross-sectional analysis of data from 243 participants in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), collected between January and July 2021. Participants underwent phone interviews assessing COVID-19 concerns, psychological distress via the PHQ-4, and material hardship. PA was measured with wrist-worn accelerometers over seven days, tracking total activity counts/day, active minutes/day, and activity fragmentation (active-to-sedentary transition probability, ASTP). We used regression models adjusted for demographic, behavioral, and health covariates. Participants (mean age = 62; 67% female) showed high psychological distress (63%) and material hardship (33%), with 39% reporting COVID-19 concerns. Concerns were linked to lower total activity counts (β = -231, 95% CI: [-459, -3]) and active minutes/day (β = -42.1, 95% CI: [-76.7, -7.4]) in adjusted models. While ASTP was higher among individuals with COVID-19 concerns, this association diminished after full adjustment. No significant links were found between material hardship or distress and PA. COVID-19-related concerns were associated with reduced and fragmented physical activity, suggesting that addressing psychosocial stressors may help improve health behaviors in this population during public health emergencies.},
}

@article {pmid42873652,
year = {2026},
author = {Pulvino, AT and Sardaro, MLS and Quinn, WG and Christopher, ER and Koenig, S and Lucore, JM and Vidal-Cruchez, O and Mallott, EK and Kuthyar, S and Lee, W and Chitta, S and Gray, S and Williams, LE and Curley, JP and Liechty, ER and Ben-Sahra, I and Amato, KR},
title = {Bile, sulphur and carbohydrate metabolic variation co-occur with host adiposity in mice colonized with primate microbiota.},
journal = {Microbial genomics},
volume = {12},
number = {10},
pages = {},
doi = {10.1099/mgen.0.001848},
pmid = {42873652},
issn = {2057-5858},
mesh = {Animals ; Mice ; Humans ; *Adiposity ; *Bile/metabolism ; Macaca mulatta ; *Sulfur/metabolism ; *Carbohydrate Metabolism ; Multiomics ; Feces/microbiology ; *Gastrointestinal Microbiome ; Cecum/microbiology ; Liver/metabolism ; Metagenomics ; Primates/microbiology ; Microbiota ; },
abstract = {Although mechanistic links between the microbiome and chronic disease are increasingly well defined, how microbiomes facilitate normal variation in host metabolism remains less clear. Building on our recent demonstration that pooled faecal inocula from different primate species can cause relative differences in mouse host adiposity, we define potential mechanisms by which this could occur. Using existing samples from germ-free mice inoculated with faecal samples from humans (Homo sapiens), rhesus macaques (Macaca mulatta) and squirrel monkeys (Saimiri boliviensis), we integrate shotgun metagenomics of caecal contents, liquid chromatography-MS-MS metabolomics of serum and caecal contents and hepatic RNA-sequencing. Our multi-omic analysis reveals that the relative increase in adiposity previously observed in macaque-donor mice is associated with differences in hepatic cysteine catabolism and bile metabolism pathway features. These data suggest that bile and sulphur co-metabolic variation may mediate increased bile pool hydrophobicity. We also observed variation in caecal microbiome composition as well as host hepatic retinol signalling and lipid metabolism between treatments. When considered together with the observation that macaque-donor mice consumed less food than the other treatment groups, our results support the hypothesis that increased bile pool hydrophobicity results in increased dietary energy extraction. Our findings provide a foundation for future mechanistic testing of new hypotheses for understanding how the intestinal microbiomes of different primate species regulate lipid homeostasis in a mouse host.},
}

Animals
Mice
Humans
*Adiposity
*Bile/metabolism
Macaca mulatta
*Sulfur/metabolism
*Carbohydrate Metabolism
Multiomics
Feces/microbiology
*Gastrointestinal Microbiome
Cecum/microbiology
Liver/metabolism
Metagenomics
Primates/microbiology
Microbiota

@article {pmid41808993,
year = {2026},
author = {Chen, X and Argos, M and Yu, B and Boerwinkle, E and Qi, Q and Kaplan, R and Franceschini, N and Sofer, T},
title = {Explaining the unexplained admixture mapping signals via rare variants: the HCHS/SOL.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41808993},
issn = {2692-8205},
support = {R01 HG013163/HG/NHGRI NIH HHS/United States ; R01 HL141824/HL/NHLBI NIH HHS/United States ; R56 HG013163/HG/NHGRI NIH HHS/United States ; },
abstract = {In admixed populations, formed by a mixing of two or more previously isolated populations, genomic segments can be traced to their ancestral populations ("ancestries"). Admixture mapping (AM) associates local ancestry with outcomes in admixed populations, detecting signals when causal variants differ in frequency or effect across ancestral populations. Prior work showed that adjusting for nearby GWAS-identified common variants does not fully explain some AM signals. Here, we assessed two approaches to explain the previously unexplained AM signal: (1) including sets of rare variants; (2) increasing the genomic region considered when searching for common variants. We studied these hypotheses comprehensively using a whole-genome sequencing dataset coupled with metabolomics from the Hispanic Community Health Study/Study of Latinos. We detected multiple sets of rare variants with replicated association with metabolite levels. Yet these rare variants appear to explain only a small fraction of the AM signal, while inclusion of common variants from a larger genomic region appears to explain the majority of the AM signals.},
}

@article {pmid42845382,
year = {2026},
author = {Schuerger, C and Biswas, S and Ng, KP and Cardone, L and Gu, X and Ganguly, S and Tohme, R and Durmaz, A and Stich, M and Lindner, DJ and Jha, B and Mian, OY and Saunthararajah, Y},
title = {Urothelial-lineage master transcription factor hub proteomics shows mechanisms impeding urothelial cancer cell differentiation.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42845382},
issn = {2692-8205},
support = {R21 CA263430/CA/NCI NIH HHS/United States ; P30 CA043703/CA/NCI NIH HHS/United States ; S10 OD018205/OD/NIH HHS/United States ; U54 CA274513/CA/NCI NIH HHS/United States ; R01 CA204373/CA/NCI NIH HHS/United States ; P01 HL146372/HL/NHLBI NIH HHS/United States ; R01 CA190578/CA/NCI NIH HHS/United States ; },
abstract = {Urothelial cancer (UC) cells of the luminal subtype exhibit partial, incomplete differentiation towards umbrella cells that line bladder lumen, seen by morphology and gene expression. Differentiation is stalled even though the cells express master transcription factors (MTFs) that drive luminal urothelial differentiation, e.g., FOXA1 and CEBPB, at levels seen in normal differentiated urothelium. We therefore analyzed the FOXA1/CEBPB MTF hub by mass spectrometry. SWI/SNF coactivator complex (CoA) components, e.g., SMARCA4, ARID1A, that read the epigenetic activation mark histone 3 lysine 27 acetylation (H3K27ac) and use ATP-hydrolysis to 'open' chromatin, were the most abundant proteins pulled-down with FOXA1/CEBPB. However, genes for these and other CoA, e.g., CREBBP, EP300 that write H3K27ac, were mutated/deleted in >95% of UCs in clinical series. Also contained in the hub were corepressors (CoR) that erase H3K27ac and 'close' chromatin, e.g., HDAC1, CHD4 - genes for these CoR were recurrently gained in UCs. Chromatin analyses showed H3K27ac-centered remodeling was needed to activate umbrella but not constitutively accessible cell growth/division/housekeeping genes. Restoring ARID1A into ARID1A-mutated UC cells using lentiviral transduction, or inhibiting CoR with siRNA or small molecules, activated umbrella genes and terminated replications. In summary, UC-genesis selects for loss- and gain-of-function of CoA and CoR respectively in the urothelial-lineage MTF hub; small molecule CoR-inhibitors are candidate remedies to renew maturation towards terminal differentiated-fates.},
}

@article {pmid42853487,
year = {2026},
author = {Collienne, L and Matsen Iv, FA},
title = {Tree Rearrangement Graphs Admit Paths of Decreasing Robinson-Foulds Distance.},
journal = {Bulletin of mathematical biology},
volume = {88},
number = {11},
pages = {},
pmid = {42853487},
issn = {1522-9602},
support = {R01 AI162611/AI/NIAID NIH HHS/United States ; R01-AI162611/NH/NIH HHS/United States ; DMS-1929284//National Science Foundation/ ; },
mesh = {*Phylogeny ; Mathematical Concepts ; *Models, Genetic ; Computer Simulation ; Computational Biology ; Algorithms ; },
abstract = {Tree rearrangements such as Nearest Neighbor Interchange (NNI) and Subtree Prune and Regraft (SPR) are commonly used to explore phylogenetic treespace. Computing distances based on them, however, is often intractable, so the efficiently computable Robinson-Foulds (RF) distance is used in practice. We investigate how the RF distance behaves along paths in the NNI and SPR graphs, where trees are nodes and edges represent single rearrangements. We show that any two trees are connected by a path along which the RF distance to the target decreases monotonically in the NNI graph and strictly in the SPR graph; we also show that a strictly decreasing NNI path does not always exist.},
}

*Phylogeny
Mathematical Concepts
*Models, Genetic
Computer Simulation
Computational Biology
Algorithms

@article {pmid42854111,
year = {2026},
author = {Hurvitz, SA and Layman, RM and Curigliano, G and Pistilli, B},
title = {Reply to: When PIK3CA Wild-Type Becomes a Biomarker Blind Spot.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2601653},
doi = {10.1200/JCO-26-01653},
pmid = {42854111},
issn = {1527-7755},
}

@article {pmid42854752,
year = {2026},
author = {McDougall, RP and Mattes, MD and Tseng, YD and Martin, EJ and Simone, CB and Robbins, JR},
title = {Assessing palliative care education and attitudes among radiation oncology residents.},
journal = {Annals of palliative medicine},
volume = {15},
number = {5},
pages = {71},
doi = {10.21037/apm-2026-0037},
pmid = {42854752},
issn = {2224-5839},
mesh = {Humans ; *Radiation Oncology/education ; *Palliative Care ; *Internship and Residency ; Male ; Cross-Sectional Studies ; Female ; *Attitude of Health Personnel ; United States ; Surveys and Questionnaires ; Adult ; Curriculum ; },
abstract = {BACKGROUND: Palliative care (PC) plays a vital role in radiation oncology (RO), but the breadth, quality, and effectiveness of formal PC education and radiation-specific palliative care (RSPC) during residency vary widely. A better understanding of how RO residents view their current training and where they see room for improvement can help guide future educational efforts. The study aims to evaluate RO residents' experiences with and attitudes toward PC and RSPC education, identify perceived gaps in training, gather suggestions for important topics, and determine preferred ways to optimally incorporate PC teaching into the existing resident schedule framework.

METHODS: From January through May 2025, a national cross-sectional survey was sent to 552 PGY-3 to PGY-5 U.S. RO residents using a REDCap-based online platform. The anonymous survey collected demographic information and inquired about the adequacy of current PC education, areas of additional instruction, and preferred learning formats and scheduling. Quantitative data were summarized descriptively, and mapped to the corresponding structured categories where relevant.

RESULTS: A total of 110 responses were received (response rate 19.9%). Most respondents identified as White (60.9%) and male (65.4%) from programs with 5-9 (40.7%) or 10-14 (35.2%) residents. While 89.0% reported access to a dedicated PC specialist, only 27.5% reported access to an RSPC specialist. Nearly all respondents supported the need for formal training in RSPC (96.0%) and general PC (84.2%). Although 45.5% reported faculty-led instruction in PC or RSPC, 15.8% indicated receiving no formal training in either area. Topics of greatest interest included symptom management, hospice care, ethical issues for PC, spinal stereotactic body radiation therapy (SBRT), and on-call management for RSPC. Residents preferred case-based, quarterly modules lasting 30-60 minutes as the most feasible educational format.

CONCLUSIONS: RO residents widely recognize the importance of structured PC and RSPC training but report significant variability in current educational offerings. Programs may enhance preparedness and patient care by integrating concise, case-based, and specialty-relevant PC content into existing curricula. These findings highlight the need for standardized national efforts to strengthen PC education within RO training.},
}

Humans
*Radiation Oncology/education
*Palliative Care
*Internship and Residency
Male
Cross-Sectional Studies
Female
*Attitude of Health Personnel
United States
Surveys and Questionnaires
Adult
Curriculum

@article {pmid42855271,
year = {2026},
author = {Sanchez-Vizcaino, C and Hippe, DS and Safwat, AA and Kharaji, M and Wang, M and Cheng, D and Canton, G and Pimentel, KD and Klein-Murrey, L and Hatsukami, TS and Yuan, C and Akoum, NW and Balu, N and Tirschwell, DL and Mossa-Basha, M},
title = {The Added Value of Vessel Wall MRI Over CTA for Differentiating Large-Artery Atherosclerotic and Cardioembolic Stroke in the Anterior and Posterior Circulations.},
journal = {AJNR. American journal of neuroradiology},
volume = {},
number = {},
pages = {},
doi = {10.3174/ajnr.A9664},
pmid = {42855271},
issn = {1936-959X},
abstract = {BACKGROUND AND PURPOSE: Differentiation between stroke etiologies is essential for secondary prevention; however, etiologic classification remains challenging in many ischemic strokes. We evaluated whether magnetic resonance vessel wall imaging (VWI) plaque markers improve computed tomography angiography (CTA)-based differentiation between cardioembolic (CE) and large-artery atherosclerotic (LAA) stroke in the anterior and posterior circulations, as a step toward improving etiologic classification beyond current criteria.

METHODS: We retrospectively included patients with unilateral anterior or posterior circulation ischemic stroke between June 2022 and April 2024 across an academic health system, classified as LAA or CE according to modified TOAST criteria. Imaging markers included CTA-derived noncalcified plaque extent (>30% stenosis), VWI-derived intracranial plaque enhancement (IPE) extent, and intraplaque hemorrhage (IPH) presence, restricted to arterial segments upstream from the infarct. Given potential territory-specific plaque differences, analyses were stratified by circulation. Multivariable logistic regression models assessed associations of CTA and VWI markers with stroke etiology. Associations with LAA were summarized using adjusted odds ratios (aOR; plaque extent variables per 1-SD increase). Overall performance for discriminating between LAA and CE etiologies was assessed using the area under the receiver operating characteristic curve (AUC).

RESULTS: Among 193 patients (median age, 70 years; 60% male), 137 had anterior circulation strokes (65 LAA, 72 CE) and 56 had posterior circulation strokes (38 LAA, 18 CE). In anterior circulation strokes, VWI markers improved discrimination over CTA alone (AUC, 0.57 for CTA alone vs 0.76 for CTA+VWI; p<0.001); CTA-derived noncalcified plaque extent (aOR, 1.7; p=0.02), IPH (aOR, 7.0; p<0.001), and IPE extent (aOR, 1.9; p=0.005) were independently associated with LAA. In posterior circulation strokes, IPE extent improved discrimination over CTA alone (AUC, 0.77 for CTA alone vs 0.84 for CTA+VWI; p=0.02); IPE extent (aOR, 2.2; p=0.02) and CTA-derived noncalcified plaque extent (aOR, 5.9; p=0.002) were independently associated with LAA. IPH was not significantly associated with posterior circulation stroke etiology (p=0.26).

CONCLUSIONS: VWI adds complementary value for differentiating LAA and CE stroke etiologies in both vascular territories, supporting a pragmatic CTA-VWI approach for etiologic characterization beyond stenosis assessment alone.},
}

@article {pmid42856579,
year = {2026},
author = {Govande, AA and Ramsey, B and Unlu, I and Amundsen, SK and Nagy, TA and Hassan, A and Smiley, M and Trautman, C and Whiteley, AT and Smith, GR and Kim, S and Lim, HC},
title = {RecBCD Prevents Bacterial Autoimmunity by Clearing Self-DNA Ends Produced During Replication Termination.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42856579},
issn = {2692-8205},
support = {R35 GM118120/GM/NIGMS NIH HHS/United States ; R35 GM143203/GM/NIGMS NIH HHS/United States ; },
abstract = {Viral-induced DNA damage triggers both eukaryotic and prokaryotic innate immunity. Here, we report that self-DNA ends generated routinely during normal termination of bacterial replication suffice to trigger the P2-encoded OLD antiphage system. Normally, these physiological triggers are cleared by the dual helicase-nuclease activities of the conserved RecBCD enzyme, which acts as an immune safeguard analogous to mammalian TREX1 exonuclease and plant DBR1 debranching enzyme. However, when this clearance fails, the transient self-DNA ends persist and are recognized by ATP-bound OLD dimers via a positively charged channel across their ATPase subunits. ATP hydrolysis then activates OLD to cleave tRNAs, causing cytotoxicity. Single-cell microscopy reveals that dozens of OLD molecules associate with kilobases of adjacent DNA, amplifying the sparse physiological DNA end signal. Our findings reveal how an endogenous byproduct poses a constant autoimmune threat in bacteria, highlighting a universal molecular conflict across kingdoms and the convergent solutions evolved to resolve it.},
}

@article {pmid42856585,
year = {2026},
author = {Merino-Galan, L and Arora, S and Glatzer, G and Jensen, M and Rajendran, A and Holland, EC and Pattwell, SS},
title = {Transcriptomic analysis reveals differential regulation of synaptic components in pediatric and adult brain tumors.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42856585},
issn = {2692-8205},
support = {K22 CA258953/CA/NCI NIH HHS/United States ; R35 CA253119/CA/NCI NIH HHS/United States ; },
abstract = {Neuronal-cancer cell interactions are a key component of brain tumor pathophysiology, yet many fundamental questions remain unanswered - with even more remaining unasked. Here, we present a comprehensive brain tumor reference map generated from bulk RNA-seq data of ~4,300 adult and pediatric brain tumors-including various glioma subtypes, medulloblastomas, ependymomas, and meningiomas-alongside ~1,400 healthy brain samples. By analyzing synaptic processes and synaptic gene expression across tumor types, we reveal the complexity of neuron-tumor crosstalk and its potential impact on patient survival. Our findings identify key synaptic signaling pathways and dysregulated patterns in brain tumors, including HNRNPH2 upregulation, a key factor in RNA processing and metabolism, in gliomas and medulloblastomas. Additionally, we highlight the role of cholinergic signaling, particularly CHRNA9, as a driver of glioma progression, which is also upregulated in WNT and Group 4 medulloblastomas, ependymomas, and meningiomas. Furthermore, P2 purinergic signaling emerges as a key player in glioma progression. These insights lay the groundwork for future studies exploring whether targeting these pathways could reprogram the tumor microenvironment toward an anti-tumor state, ultimately leading to novel therapeutic strategies and improved patient outcomes.},
}

@article {pmid42858234,
year = {2026},
author = {Becker, H and Walter, B and Haeusser, LA and Trampert, J and Zago, M and Surender, S and Maise, L and Volos, P and Erdmann, S and Kuhlburger, L and Falkner, A and Tsiami, F and Dörner, L and Maric, M and Skotnicki, A and Jägle, H and Echeverria, D and Jackson, S and Tripathi, A and Segarra-Visent, X and Bhandari, A and Beck, S and Tatagiba, M and Nahnsen, S and Claassen, M and Haraszti, R and Szulzewsky, F and Holland, EC and Merk, DJ and Tabatabai, G},
title = {Fanconi anemia pathway disruption drives lomustine sensitivity in glioma.},
journal = {Neuro-oncology},
volume = {},
number = {},
pages = {},
doi = {10.1093/neuonc/noag254},
pmid = {42858234},
issn = {1523-5866},
abstract = {BACKGROUND: Therapeutic options for progressive glioblastoma remain limited, with chlorethyl-cyclohexyl-nitrosourea (CCNU, lomustine) among the approved treatments. Beyond MGMT gene promoter methylation, molecular determinants of CCNU sensitivity or resistance are ill- defined.

METHODS: We employed genome-wide functional knockout screening using the CRISPR-Cas9 technology to identify and subsequently validate modulators of response to CCNU in experimental glioma. We established an immunocompetent glioma mouse model to enable functional interrogation of Fanconi anemia pathway (FA) genes in tumor growth and synthetic lethal interactions in vivo using the RCAS/tv-a somatic gene delivery system.

RESULTS: Multiple FA pathway members recurrently emerged as potent synthetic lethal interactors of CCNU treatment. In vivo knockdown of Fancm accelerated tumor onset and significantly increased CCNU sensitivity. Consistently, FA pathway inhibition enhanced CCNU efficacy across in vitro, ex vivo and in vivo models.

CONCLUSION: Together, these findings identify FA pathway components as key synthetic lethal interactors of CCNU response and reveal a therapeutically actionable vulnerability in glioblastoma.},
}

@article {pmid42858314,
year = {2026},
author = {Applin, SN and Andrasik, MP and Hawes, SE and Dickson, K and Blakey, W},
title = {Meeting patients where they are: The Tacoma MAX clinic's collaborative low-barrier approach to HIV care.},
journal = {AIDS care},
volume = {},
number = {},
pages = {1-11},
doi = {10.1080/09540121.2026.2744848},
pmid = {42858314},
issn = {1360-0451},
abstract = {In Tacoma, Washington, people with HIV (PWH) face significant barriers to care. This study compares viral suppression and patient-centered outcome effectiveness of co-located Ryan White (RW) and MAX (low-barrier, walk-in, engaging previously disengaged PWH with unsuppressed viral loads (VL) clinics.Mixed-methods, prospective cohort study of MAX/RW participants surveyed/interviewed at baseline, 6 and 12 months, assessing VL suppression (86 qualitative interviews coded thematically across six health/medical care domains). Eligibility criteria: VL >200 copies/mL (last 12 months), out of care ≥12 months, or facing engagement barriers. EMR VL data were collected between January 2020 and February 2025.Participants enrolled: 30 MAX and 70 RW. Viral suppression by timeline: -6 months (69.6% MAX, 78.4% RW; p = 0.4). -2.5 years (60.0% MAX, 92.1% RW; p = 0.003). MAX had higher baseline rates of housing instability (p = 0.11) and mental illness (p = 0.02) but cited immediate access, non-judgmental care, and wraparound services as being "lifesaving", with fewer unmet mental health needs and greater care access and education.Low-barrier models play a vital role in re-engaging PWH facing barriers. While RW achieved higher long-term viral suppression, MAX achieved improved trust, health literacy, and retention-foundations for long-term health. Integrated, patient-centered approaches can complement traditional care and address service gaps.},
}

@article {pmid42848909,
year = {2026},
author = {Yu, Q and Kim, H and Seidel, S and Acosta-Clark, JF and Martin, BK and O'Connor, K and Daza, RM and Gasperini, M and Nathans, JF and Lam, M and Gamo, E and Vijay Kumar, S and Kuo, L and Lalanne, JB and Simeonov, KP and Pepper, M and Trapnell, C and Gray, JM and Choi, J and Qiu, C and Shendure, J},
title = {A DNA Typewriter records the cell lineage history of a mouse, from zygote to late organogenesis.},
journal = {Science (New York, N.Y.)},
volume = {},
number = {},
pages = {eael0508},
doi = {10.1126/science.ael0508},
pmid = {42848909},
issn = {1095-9203},
abstract = {Mammalian biology unfolds over time, within tissues and organs opaque to our eyes and instruments. We applied DNA Typewriter, a sequential molecular recorder, to record the cell lineage of a mouse over nearly two weeks of development. From one embryo, we reconstruct a time-calibrated, parsimony-supported, zygote-rooted phylogeny of 1.28 million transcriptionally profiled cells. A burst of editing unequivocally marks the daughters of the first cleavage, which serve as inline replicates. We quantify clonal dominance arising during gastrulation. Tree siblings share cell type far above chance; heterotypic siblings mark terminal differentiations. Temporal sweeps of clade co-occurrence recover a dated hierarchy of cell-type couplings; imputed labels for internal nodes recapitulate known state paths. A lineage-anchored ontogeny of mammalian development, long out of reach, is coming into view.},
}

@article {pmid42852882,
year = {2026},
author = {Gómez-Garzón, C and O'Brien, VP and Chen, Q and Garman, KS and Salama, NR},
title = {Metaplasia creates a permissive niche for select Fusobacterium species in the stomach.},
journal = {mBio},
volume = {},
number = {},
pages = {e0174726},
doi = {10.1128/mbio.01747-26},
pmid = {42852882},
issn = {2150-7511},
abstract = {Infection with Helicobacter pylori is the major risk factor for gastric cancer worldwide; yet the exact mechanisms behind this link remain unclear. H. pylori-associated tissue changes often disrupt the gastric microbiome, enabling secondary gastric colonization by oral bacteria. Among these secondary colonizers, Fusobacterium species have documented associations with several gastrointestinal cancers. We found that both F. animalis and F. nucleatum invade cultured human gastric adenocarcinoma cells, but F. animalis exhibited higher adherence and invasion, and hypoxic conditions promoted higher bacterial survival. Both adherence and invasion were inhibited by exogenous GalNAc, a glycan commonly observed in membrane glycoproteins of adenocarcinoma cells and a target of the fusobacterial adhesin Fap2. Using a mouse model of stomach metaplasia, we found that F. animalis colonized gastric tissue only after metaplasia onset, growing in multispecies biofilms in the mucus layer, while F. nucleatum colonized neither healthy nor metaplastic gastric tissue. Metaplasia led to upregulation of Gal-GalNAc in the stomach, and reduced gastric acidity allowed higher F. animalis loads in this model. By contrast, inflammation and the presence of H. pylori did not significantly influence stomach colonization by F. animalis. Further assessment of additional Fusobacterium species and strains revealed that whereas all tested species can invade gastric cancer cells in vitro, only F. animalis and F. polymorphum robustly colonize the metaplastic gastric tissue of the mouse model similar to F. animalis. Overall, our data support a model in which H. pylori-induced metaplasia makes the stomach susceptible to secondary infection by other cancer-associated microbes, including some Fusobacterium species.IMPORTANCEHelicobacter pylori infection is the primary risk factor for gastric cancer worldwide, yet the underlying cancer-promoting mechanisms are not fully defined. Our study shows that metaplasia, a precancerous condition typically triggered by H. pylori and characterized by specific changes in gene expression and tissue remodeling, can enable secondary infection by other cancer-associated bacteria. Specifically, we found that certain species of the genus Fusobacterium, linked to several gastrointestinal cancers, colonize the stomach only after the onset of metaplasia. Metaplasia-associated changes in the stomach include altered surface sugars and reduced acidity, which together may create a more permissive environment for bacterial growth. Our findings support a model in which disruptions of gastric tissue architecture induced by chronic H. pylori infection facilitate colonization by other cancer-related bacteria, contributing to the growing body of evidence highlighting the role of bacteria in cancer development.},
}

@article {pmid42844522,
year = {2026},
author = {Bhatia, S and D'Angelo, S and Nghiem, P},
title = {Perspectives on 10 years of Immune Checkpoint Inhibitors in Merkel Cell Carcinoma: A Podcast.},
journal = {Targeted oncology},
volume = {},
number = {},
pages = {},
pmid = {42844522},
issn = {1776-260X},
abstract = {Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer with a poor prognosis, particularly in patients with advanced disease. The introduction of immune checkpoint inhibitors (ICIs) approximately 10 years ago has dramatically improved outcomes for patients with advanced MCC. Current US Food and Drug Administration-approved ICIs in this setting include the PD-L1 inhibitor avelumab and PD-1 inhibitors pembrolizumab and retifanlimab. In this podcast, we summarize key studies of ICIs in advanced MCC, including clinical trials and real-world studies, and discuss clinical evidence related to practical considerations, such as elective discontinuation of ICI treatment, and treatment of patients with immunocompromised or immunosuppressed status. We also discuss initial findings from studies of ICI-based combinations in patients with advanced MCC and ICI treatment in earlier stages of MCC, and highlight the emerging role of circulating tumor DNA for predicting disease recurrence. Overall, these developments demonstrate the positive impact of ICIs in the treatment of MCC and illustrate ongoing efforts to further improve patient outcomes.},
}

@article {pmid42845039,
year = {2026},
author = {Torka, P and Bock, AM and Hao, P and Xu, Y and Thiruvengadam, SK and Luttwak, E and Sekaran, K and Sano, D and Vaughn, J and Sharp, J and Major, A and Patel, V and Smilnak, G and Araujo, N and Mynam, R and Reef, D and Palmeri, M and Gerber, D and Lee, C and Baek, G and Falade, A and Iqbal, M and Shah, HR and Geethakumari, PR and Durani, U and Di, M and Niu, A and Cherng, HJ and Rhodes, JM and Grover, N and Pophali, P and Feldman, T and Shanmugasundaram, K and Svoboda, J and Voorhees, T and Diefenbach, C and Karimi, Y and Karmali, R and Herrera, A and Epperla, N},
title = {Nivolumab with doxorubicin, vinblastine, and dacarbazine in older adults with classic Hodgkin lymphoma: do S1826 results hold up in the real world?.},
journal = {Haematologica},
volume = {},
number = {},
pages = {},
doi = {10.3324/haematol.2026.301545},
pmid = {42845039},
issn = {1592-8721},
abstract = {Older adults (OA, ≥60 years) with classic Hodgkin lymphoma (cHL) have historically experienced inferior outcomes compared to younger patients. Nivolumab in combination with doxorubicin, vinblastine, and dacarbazine (NAVD) has demonstrated high efficacy in clinical trials, but real-world data in OA are limited. We conducted a multicenter retrospective study across 20 centers in patients with newly diagnosed advanced stage cHL treated with NAVD and analyzed outcomes in OA across the aging spectrum. Among 327 total patients, 81 (25%) were ≥60 years, with most OA presenting with stage IV disease (58%) and B symptoms (57%). Anygrade and ≥grade 3 AEs occurred in 88% and 67% of OA, respectively. Prophylactic growth factors were used in most OA (82%) which led to low rates of febrile neutropenia (12%) and infection (12%) despite 52% ≥grade 3 neutropenia. Immune-related AEs occurred in 29% (12% ≥grade 3) and treatment was discontinued due to toxicity in 10% of OA. Interim overall (ORR) and complete response rates (CRR) were 100% and 81.6%, end-of-treatment rates were 88% and 82.6%, respectively. At a median follow-up of 12.6 months, 1-year progression-free survival (PFS) and overall survival (OS) in OA were 91.5% and 98.6%, respectively. OS was inferior in OA compared with patients.},
}

@article {pmid42845905,
year = {2026},
author = {Alsulami, A and Bogdani, M and MacLean, EL and Keene, CD and McGrath, S and , and Latimer, CS and Moreno, JA},
title = {Alzheimer's disease neuropathological characterization of the dog brain and relationship to biofluid biomarkers and cognitive function.},
journal = {NPJ dementia},
volume = {2},
number = {1},
pages = {88},
pmid = {42845905},
issn = {3005-1940},
support = {P30 AG066509/AG/NIA NIH HHS/United States ; R24 AG073137/AG/NIA NIH HHS/United States ; U19 AG057377/AG/NIA NIH HHS/United States ; },
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting more than 55 million people worldwide and is characterized by cognitive decline, amyloid-beta (Aβ) plaques, and neurofibrillary tangles. Although transgenic rodent models have advanced understanding of AD, they do not fully replicate the spontaneous, age-related nature of human disease. Companion dogs naturally develop age-associated cognitive decline and AD-like neuropathology, making them a valuable translational model. This study characterized Aβ deposition, phosphorylated tau (pTau181) pathology, and neuritic plaque pathology in aged canine brains using neuropathologic assessment methods adapted from human AD frameworks (Thal, Braak, and CERAD), and examined associations with cognitive status and plasma biomarkers. Postmortem brain tissues from 24 client-owned senior dogs were evaluated and integrated with antemortem Canine Cognitive Dysfunction Rating (CCDR) scores and plasma biomarker measurements. Senior dogs exhibited Aβ deposition consistent with early Thal-like regional involvement, variable regionally restricted pTau181 pathology, and an absence of neuritic plaques. Quantitative analyses showed greater Aβ burden in cognitively impaired dogs, while age was the strongest predictor of regional Aβ accumulation. Plasma glial fibrillary acidic protein (GFAP) concentrations were positively correlated with Aβ plaque burden, whereas other biomarkers were not. These findings indicate that aged dogs develop early-stage AD-like pathology and support their utility as a naturally aging model for studying preclinical AD mechanisms and translational biomarkers.},
}

@article {pmid42846115,
year = {2026},
author = {Palazzo, L and Luce, C and Vasavada, A and Mettert, K and Gao, H and Ralston, JD and Bezman, N and Green, BB and Rogers, K and Anderson, ML and Su, YR and Triplette, M and Carter-Bawa, L and Wernli, KJ},
title = {I need it. Without it, I wouldn't have gone, and I do want to go: patient perspectives on the acceptability and appropriateness of two patient-centered interventions to improve adherence to annual lung cancer screening.},
journal = {Frontiers in health services},
volume = {6},
number = {},
pages = {1810956},
pmid = {42846115},
issn = {2813-0146},
support = {R01 CA262015/CA/NCI NIH HHS/United States ; },
abstract = {INTRODUCTION: Low adherence to annual lung cancer screening (LCS) has tempered mortality benefits in clinical practice. Herein, we assessed the acceptability and appropriateness of two patient-centered interventions addressing adherence barriers to annual LCS.

METHODS: Participants were Kaiser Permanente Washington members, aged 50-78 years, who participated in a pragmatic randomized trial ("The Larch Trial"). The trial tested: (1) health communication including a video to improve patient knowledge of timeliness to return; and (2) outreach reminders to patients to schedule annual screenings after their primary care provider (PCP) ordered a scan without an appointment. Participants, randomly sampled on sex, race/ethnicity, tobacco status, and trial arm, completed semistructured, virtual interviews that lasted for 60 min. The interviews explored intervention acceptability and appropriateness, and barriers and facilitators to both. Transcripts were analyzed using a rapid group analysis process informed by the Consolidated Framework for Implementation Research. Identified themes were second-coded for acceptability and appropriateness in accordance with the Implementation Outcomes Framework.

RESULTS: A total of 32 participants were interviewed; 66% were non-Hispanic white, 53% male, and 53% currently use tobacco. The participants found the interventions acceptable and appropriate with variations by LCS history and information needs. Some participants found the video helpful and comforting, especially first-time screeners. Other participants, particularly those engaged in annual LCS, found that the video lacked new information. The participants strongly endorsed the reminder intervention for encouraging LCS and clarifying the timing of repeat screening. Most participants endorsed the annual screening scan ordered without a PCP visit. The participants preferred the multimodal delivery of reminders for reinforcement. Facilitators of acceptability and appropriateness included video design and perceived educational value, and an electronic health record ecosystem supporting communication aligned with routine practice. Barriers included content perceived as not novel, lack of information to address specific needs, and excessive reminders.

DISCUSSION: Video-based content in LCS is generally acceptable and appropriate to patients if tailored by LCS history. Patient outreach reminders are acceptable and appropriate when mirroring other healthcare system communications. Participants already engaged in LCS did not feel they needed to see their PCP one year later for repeat screening (within 1 year). Future studies should test interventions in other populations and healthcare systems using different communication strategies.

CLINICAL TRIAL REGISTRATION: clinicaltrials.gov, identifier #NCT05747443.},
}

@article {pmid42847095,
year = {2026},
author = {Fox, JW and Roble, G},
title = {Regional Consortia of Cancer Center Shared Resources: Models for Collaborative Infrastructure and the Emergence of a National Alliance.},
journal = {Journal of biomolecular techniques : JBT},
volume = {37},
number = {3},
pages = {7-12},
pmid = {42847095},
issn = {1943-4731},
mesh = {Humans ; National Cancer Institute (U.S.) ; United States ; Cooperative Behavior ; *Cancer Care Facilities/organization & administration/economics ; *Neoplasms ; Interinstitutional Relations ; },
abstract = {Shared resource facilities are foundational to the scientific productivity of National Cancer Institute (NCI)-designated cancer centers, yet institutional silos frequently constrain member access to specialized instrumentation and expertise. Interinstitutional consortia of shared resources offer a pragmatic solution, enabling reciprocal service access at internal rates while preserving institutional autonomy. Here we describe two established regional consortia, the Mid-Atlantic Cancer Center Shared Resource Consortium (MACCSRC) and the Fred Hutchinson/University of Washington/Seattle Children's NCI Comprehensive Cancer Center Consortium-examining their organizational frameworks, operational outcomes, and lessons learned. Finally, we introduce the recently organized National Alliance for Cancer Center Shared Resources and discuss how it may serve as an integrating infrastructure connecting regional networks on a national scale. Key considerations for consortium formation, including governance, intellectual property, pricing harmonization, and cost allocation, are addressed.},
}

Humans
National Cancer Institute (U.S.)
United States
Cooperative Behavior
*Cancer Care Facilities/organization & administration/economics
*Neoplasms
Interinstitutional Relations

@article {pmid42844260,
year = {2026},
author = {Eichholz, K and Okoye, AA and Varco-Merth, BD and Gong, J and Bui, J and Hou, J and Kiem, HP and Hayball, D and Hoenerhoff, M and Robinson, ST and Peterson, CW and Corey, L and Corey, D},
title = {Safety of Autologous Infusion of CER T Cells in Nonhuman Primates.},
journal = {AIDS research and human retroviruses},
volume = {},
number = {},
pages = {8892229261490969},
doi = {10.1177/08892229261490969},
pmid = {42844260},
issn = {1931-8405},
abstract = {Cellular immunotherapies have shown great promise in the treatment of various diseases. Chimeric engulfment receptor (CER)-engineered T cells were developed to utilize the extracellular T-cell immunoglobulin and mucin domain-containing 4 (TIM-4) domain and intracellular engulfment signaling domains to target and enhance phagocytosis and T-cell cytotoxic function. These processes are activated through TIM-4 binding with phosphatidylserine (PS), a pro-phagocytic "eat me" signal. HIV infection has been shown to induce extracellular PS exposure shortly after infection, and engineered CER T cells have been shown to kill CD4[+] T cells infected with simian immunodeficiency virus (SIV) in vitro. In this study, we infused two rhesus macaques (RMs) with CER-1236 T cells (the iteration of CER T cells currently moving forward in human clinical trials for cancer) and evaluated safety, the tissue distribution of the CER-1236 T cells, and antiviral activity against SIV (SIVmac239). Prior to infusions, RMs underwent SIV infection, antiretroviral therapy (ART), and ART cessation. The infusions were well tolerated. Neither of the macaques exhibited clinical evidence of illness nor changes in vital signs, serum chemistry, hematology, or other evaluated physiological parameters beyond what is typically observed with SIV infection. Post-infusion proliferation of CER T cells in PBMC was limited and seen with cells manufactured by the Prodigy system. Histologic and flow cytometry evaluation from post-infusion tissue biopsies and necropsy revealed tissue detection of CER T cells in bronchoalveolar lavage fluid with intermittent detection of infused cells in lymphoid tissue in concert with the limited expansion of T cells in PBMC. No laboratory or clinical evidence of hepatic, splenic, bone marrow, or CNS alterations was noted, and no evidence of in vivo suppression of SIVmac239 was observed as a result of the infusions. The CER-1236 T cell infusions were not associated with any discernable histopathological toxicity. This safety profile of CER-1236 T cells in nonhuman primates portends well for its potential for clinical development, especially for tumors with high expression of the tissue damage receptor PS. Optimization of in vivo functionality will be required for CER T cells to be effective against HIV infection.},
}

@article {pmid42844465,
year = {2026},
author = {Kim, YS and Arora, S and Young, D and Tsou, A and Shiuan, A and Wladyka, CL and Rudoy, D and Kim, JY and Waters, JA and Schuster, SL and Coleman, IM and Kapur, M and Sobczyk, M and Katanski, CD and Bayat Tork, AM and Zhang, W and Nelson, PS and Ha, G and Haffner, MC and Corey, E and Morrissey, C and Wang, Y and Subramaniam, AR and Lee, JK and Ackerman, SL and Pan, T and Hsieh, AC},
title = {tRNA dosage regulates lineage dependency and resistance in prostate cancer.},
journal = {Nature},
volume = {},
number = {},
pages = {},
pmid = {42844465},
issn = {1476-4687},
abstract = {Lineage plasticity underlies therapeutic resistance in cancer[1,2], yet the translational mechanisms that enable this phenotypic flexibility remain largely unknown. Here using prostate cancer as a model of lineage dependence, we performed unbiased small RNA sequencing and identified tRNA1[Arg](UCU) as a regulator of lineage transitions and therapy resistance. tRNA1[Arg](UCU) is capable of reprogramming lineage dependence, which can be tuned to restore sensitivity to therapies that target the androgen receptor. We identify TARDBP and ZSCAN29 as DNA-binding proteins that directly engage the genomic locus of tRNA1[Arg](UCU) to regulate its expression, a result that highlights the importance of non-canonical tRNA-specific gene regulation. Mechanistically, tRNA1[Arg](UCU) controls a translational program centred on SWI/SNF chromatin remodellers, which is necessary to maintain lineage fidelity. In patients, tRNA1[Arg](UCU) is downregulated in neuroendocrine prostate cancer and its loss is associated with accelerated metastasis and poor survival. These findings uncover a previously unrecognized tRNA-specific regulatory axis that links codon biology to lineage dependence and therapy resistance in prostate cancer.},
}

@article {pmid42327143,
year = {2026},
author = {Xia, P and Li, H and Ji, Y and Ju, CW and Pan, Y and Mo, J and Zhu, X and Zhao, L and Lv, R and Niewold, E and Fernandez, M and Ai, Y and Wei, J and Bradley, RK and Wang, L and Abdel-Wahab, O and Liu, B and He, C},
title = {A U1-U3 snRNA-snoRNA interaction couples SF3B1 mutation to chromatin-state rewiring and genome instability.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42327143},
issn = {2692-8205},
abstract = {Mutations in spliceosome factors such as SF3B1 are recurrent across human diseases, including myelodysplastic syndromes and leukemia[1-4], yet splicing defects alone do not fully explain the widespread chromatin alterations and genome instability in mutant cells[5]. Here, by comprehensively mapping snRNA-directed RNA-RNA interactions, we identify two previously unrecognized interaction motifs in U1 snRNA beyond canonical 5' splice-site pairing[6,7]. These motifs enable U1 RNA to i) bind intronic and other chromatin-associated RNA (caRNA) regions outside of splice sites, and ii) base pair specifically with snoRNA. We uncover a U1-U3 snRNA-snoRNA interaction that recruits the H3K36 methyltransferase SETD2 to caRNA, promoting gene-body H3K36me3 and antagonizing H3K27me3 to modulate chromatin accessibility. The snRNA-snoRNA interface is essential for this previously unrecognized layer of chromatin and transcriptional regulation mediated through SETD2. SF3B1 mutation enhances U1-U3 binding and increases the association of the U1-U3 complex with caRNA, driving chromatin-accessibility remolding, R-loop formation, DNA damage, and copy-number abnormalities that promote tumorigenesis. A U1-specific 2'-O-methoxyethyl antisense oligonucleotide that selectively blocks U1-U3 pairing suppresses these genomic abnormalities, reduces leukemic infiltration, and prolongs survival in xenograft and patient-derived models, establishing pathological snRNA-snoRNA rewiring as a critical driver of SF3B1-mutant leukemogenesis.},
}

@article {pmid42327147,
year = {2026},
author = {de Los Rios Kobara, I and Mangalanathan, UM and Deline-Caballero, S and Pinedo, K and Stabile, M and Bernal, CE and Itell, HL and Chohan, V and McClelland, RS and Mandaliya, K and Overbaugh, J and Blish, CA},
title = {Viral load-driven systemic immune exhaustion is an enabler of antibody breadth in HIV infection.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42327147},
issn = {2692-8205},
abstract = {A broadly neutralizing response to a human immunodeficiency virus (HIV) vaccine is a major goal of the field, yet the determinants of antibody breadth remain poorly defined. Antibody responses to HIV evolve over years of infection, developing unusual features such as high mutation rates in the subset of individuals that acquire breadth. Using single-cell RNA sequencing, single-cell proteomics, and plasma neutralization assays in a longitudinal Kenyan cohort of treatment-naive women living with HIV, we identify systems-level immune correlates of antibody breadth. Broad and narrow neutralizers diverge early in infection along a viral load-driven axis with broad neutralizers exhibiting greater viral loads and CD4 T cell decline; concurrently, NK cells, CD8 T cells, and monocytes, broad neutralizers displayed greater magnitude of immune activation in early infection, followed by exhaustion in late infection. This functional decline may dampen NK cell-mediated pruning of T follicular helper cells, creating a permissive environment for sustained germinal center activity and antibody maturation. Narrow neutralizers, by contrast, maintain functional cellular immunity but lack the antigenic pressure and permissive exhaustive state associated with breadth. Together, these findings suggest that antibody breadth in HIV infection reflects failed viral control rather than a successful antiviral response with implications for vaccination and cure strategies that must balance cellular and humoral immunity.},
}

@article {pmid42842874,
year = {2026},
author = {Adderley, NA and Turner, J and Carpenter, PA and Cheng, GS},
title = {Interpreting pulmonary function tests in allogeneic hematopoietic cell transplant recipients.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2026022101},
pmid = {42842874},
issn = {2473-9537},
abstract = {Pulmonary complications are a significant cause of non-relapse mortality in allogeneic hematopoietic cell transplant (HCT) recipients. Pulmonary function tests (PFTs) are recommended to screen for asymptomatic lung function decline that precedes overt disease. HCT clinicians must understand the critical importance of PFTs in the post-HCT context and be able to identify abnormalities for timely intervention. This article provides a concise summary of contemporary PFT interpretation practices, tailored to clinicians caring for this complex patient population. Key principles, including comparison of pre-transplant and routine post-transplant studies, the importance of longitudinal assessments, and consideration of the clinical context of the HCT survivor, are illustrated through case vignettes. We review remaining fundamental questions about the application of PFTs post-transplant and suggest a path towards improved implementation and utilization of PFT data to guide clinical decision-making.},
}

@article {pmid42842904,
year = {2026},
author = {Hurvitz, SA},
title = {Advances in Systemic Treatment of Breast Cancer.},
journal = {The New England journal of medicine},
volume = {395},
number = {14},
pages = {1409-1425},
doi = {10.1056/NEJMra2500695},
pmid = {42842904},
issn = {1533-4406},
mesh = {Female ; Humans ; *Antineoplastic Agents/pharmacology/therapeutic use ; Biomarkers, Tumor/antagonists & inhibitors/blood/genetics/metabolism ; *Breast Neoplasms/genetics/mortality/pathology/therapy ; Erb-b2 Receptor Tyrosine Kinases/analysis/antagonists & inhibitors/metabolism ; Immunoconjugates/pharmacology/therapeutic use ; *Molecular Targeted Therapy/methods ; Precision Medicine/methods ; Immune Checkpoint Inhibitors/pharmacology/therapeutic use ; Circulating Tumor DNA/blood ; Neoplasm Staging ; *Antineoplastic Combined Chemotherapy Protocols/pharmacology/therapeutic use ; Protein Kinase Inhibitors/pharmacology/therapeutic use ; Receptors, Estrogen/analysis/antagonists & inhibitors/metabolism ; Receptors, Progesterone/analysis/antagonists & inhibitors/metabolism ; Antineoplastic Agents, Hormonal/pharmacology/therapeutic use ; Class I Phosphatidylinositol 3-Kinases/antagonists & inhibitors/genetics/metabolism ; Progression-Free Survival ; Neoadjuvant Therapy/methods ; Chemotherapy, Adjuvant/methods ; },
abstract = {Systemic therapy for breast cancer has evolved rapidly since 2020, driven by the expansion of targeted therapies, antibody-drug conjugates, and immunotherapy across biologic subtypes. The integration of tumor molecular profiling and germline testing has enabled increasingly personalized, biomarker-guided treatment strategies. In hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative disease, cyclin-dependent kinase 4 and 6 inhibitors remain foundational, whereas phosphatidylinositol 3-kinase pathway inhibitors, oral selective estrogen-receptor degraders, and antibody-drug conjugates have transformed disease management after endocrine resistance. In HER2-positive disease, antibody-drug conjugates - particularly trastuzumab deruxtecan - have improved outcomes and are being used in earlier lines of therapy, a development that is reshaping treatment paradigms. In triple-negative breast cancer, immune checkpoint inhibitors have improved outcomes in both metastatic and early-stage disease. Across subtypes, advances in curative therapy increasingly emphasize risk-adapted escalation and de-escalation of treatment. Ongoing challenges include improving treatment sequencing, identifying predictive biomarkers, integrating emerging tools such as analysis of circulating tumor DNA, and ensuring equitable access to high-cost therapies.},
}

Female
Humans
*Antineoplastic Agents/pharmacology/therapeutic use
Biomarkers, Tumor/antagonists & inhibitors/blood/genetics/metabolism
*Breast Neoplasms/genetics/mortality/pathology/therapy
Erb-b2 Receptor Tyrosine Kinases/analysis/antagonists & inhibitors/metabolism
Immunoconjugates/pharmacology/therapeutic use
*Molecular Targeted Therapy/methods
Precision Medicine/methods
Immune Checkpoint Inhibitors/pharmacology/therapeutic use
Circulating Tumor DNA/blood
Neoplasm Staging
*Antineoplastic Combined Chemotherapy Protocols/pharmacology/therapeutic use
Protein Kinase Inhibitors/pharmacology/therapeutic use
Receptors, Estrogen/analysis/antagonists & inhibitors/metabolism
Receptors, Progesterone/analysis/antagonists & inhibitors/metabolism
Antineoplastic Agents, Hormonal/pharmacology/therapeutic use
Class I Phosphatidylinositol 3-Kinases/antagonists & inhibitors/genetics/metabolism
Progression-Free Survival
Neoadjuvant Therapy/methods
Chemotherapy, Adjuvant/methods

@article {pmid42840237,
year = {2026},
author = {Omame, A and Xiao, Y and Han, Q and Iyaniwura, SA},
title = {Editorial: Mathematical Modelling and data analysis in infectious diseases.},
journal = {Frontiers in public health},
volume = {14},
number = {},
pages = {1975806},
pmid = {42840237},
issn = {2296-2565},
}

@article {pmid42840270,
year = {2023},
author = {Henikoff, S},
title = {The epigenetic landscape: An evolving concept.},
journal = {Frontiers in epigenetics and epigenomics},
volume = {1},
number = {},
pages = {1176449},
pmid = {42840270},
issn = {2813-706X},
abstract = {The epigenetic landscape was a visual metaphor introduced in the mid-twentieth century to illustrate the genetic control of embryonic differentiation. Although the popular understanding of epigenetics has since expanded to include gene and chromosomal mechanisms in all contexts, the landscape metaphor provides a unifying concept centered around processes that establish and maintain cellular memory. However, over the decades the term epigenetics has been also used to describe some non-genetic processes that bear little or no resemblance to the traditional concept of an epigenetic landscape. By establishing Frontiers in Epigenetics and Epigenomics, we aim to provide authors and readers a forum and an outlet for research that is centered around the original concept of an epigenetic landscape. Thanks in large part to exciting advances in epigenomic technologies, we expect that a deeper understanding of cellular memory will translate into new strategies for medicine, agriculture, and environmental health.},
}

@article {pmid42840546,
year = {2025},
author = {Xu, Y and Henikoff, S and Ahmad, K},
title = {Chromatin profiling for everyone: FFPE-CUTAC for the theory and practice of modern molecular biology.},
journal = {Frontiers in epigenetics and epigenomics},
volume = {3},
number = {},
pages = {1753710},
pmid = {42840546},
issn = {2813-706X},
abstract = {In 2025, together with the Fred Hutch Summer Undergraduate Research and Summer High School Internship programs, we developed and implemented a laboratory genomics research experience to introduce students to modern molecular biology techniques and bioinformatics. The course centered around using a new method we had developed in 2023 that uses readily available fixed tissue sections on glass slides. Students performed a series of steps to tagment genomic locations of RNA Polymerase II and then used PCR to enrich libraries for next-generation sequencing in a core facility. Students then visualized their data in genomic browser tracks and assessed the results. At the end of the summer, students prepared and presented their work and experiences in seminar format to their cohorts. Overall, the technical simplicity of on-slide chromatin profiling introduced the students to laboratory practice and current techniques in genomics, bioinformatics, and medical sciences.},
}

@article {pmid42840830,
year = {2026},
author = {Morales, J and Zablocki, RW and Hartman, SJ and Kumar, A and Kumar, A and Carlson, JA and Greenwood-Hickman, MA and Hibbing, PR and Staudenmayer, J and Di, C and Zou, J and Nguyen, S and LaCroix, AZ and Dillon, L and Ryu, H and Shao, L and Shi, W and Tuz-Zahra, F and Natarajan, L},
title = {Validating the Longitudinal Assessment of Sedentary Behavior in a Randomized Controlled Trial via a Deep Learning Algorithm.},
journal = {Journal for the measurement of physical behaviour},
volume = {9},
number = {},
pages = {},
pmid = {42840830},
issn = {2575-6613},
support = {P01 AG052352/AG/NIA NIH HHS/United States ; R01 DK114945/DK/NIDDK NIH HHS/United States ; R01 HL130483/HL/NHLBI NIH HHS/United States ; R01 HL168535/HL/NHLBI NIH HHS/United States ; },
abstract = {BACKGROUND: Sedentary behavior (SB) is a risk factor for cardiometabolic disease. Existing cut-points of hip-worn accelerometers to quantify SB underestimate sedentary bout durations by ignoring posture. To address this, we previously developed CHAP, Convolutional Neural Network Hip Accelerometer Posture, a deep learning algorithm that predicts sitting and breaks from sitting. In this study, we applied CHAP to a randomized controlled trial to externally validate its accuracy for classifying sitting versus non-sitting and estimating intervention-related changes in SB.

METHODS: CHAP was applied to 30Hz-tri-axial hip-worn ActiGraph-GT3X+ (AG) accelerometer data from free-living postmenopausal women who are overweight (≥55-yrs) in the Rise for Health RCT(n=406). CHAP-predicted SB accuracy (e.g., sensitivity) and daily pattern metrics (e.g., total sedentary time) were compared to a ground-truth device activPAL (AP) and standard cut-point method (AG100), at two timepoints for intervention arms-Healthy Living (control), Reduce Sitting, and Increase Transitions.

RESULTS: CHAP's SB accuracy metrics were above 84.8%. Mean (SE, p) intervention effect estimates (mean change, intervention minus controls) from generalized estimating equation models for (I) total sedentary time were AP 65.1 min/day (16.2, p<0.001), CHAP 38.2 min/day (15.4, p=0.013), and AG100 0.28 min/day (13.9, p=0.98) (Reduce Sitting); (II) breaks from SB were AP 22/day (4.3, p<0.001), CHAP 4/day (1.5, p=0.003), and AG100 <1/day (2.1, p=0.860) (Increase Transitions).

CONCLUSIONS: This study validated CHAP on an independent cohort. CHAP exhibited high prediction accuracy, and although less sensitive than AP, CHAP detected changes in SB more effectively than AG100. Thus, CHAP could make a strong contribution to SB intervention research.},
}

@article {pmid42841240,
year = {2026},
author = {Thomas, PG},
title = {Entering the Age of Specificity in T Cell Immunity.},
journal = {Immunological reviews},
volume = {343},
number = {1},
pages = {e70184},
pmid = {42841240},
issn = {1600-065X},
support = {75N93021C00016//National Institute of Allergy and Infectious Diseases/ ; 75N93021C00016/OD/NIH HHS/United States ; 75N93019C00052/OD/NIH HHS/United States ; 75N93019C00052//National Institute of Allergy and Infectious Diseases/ ; AI136514//National Institute of Allergy and Infectious Diseases/ ; R01 AI136514/AI/NIAID NIH HHS/United States ; },
mesh = {Humans ; Animals ; *T-Lymphocytes/immunology/metabolism ; Receptors, Antigen, T-Cell/metabolism/genetics ; *Epitopes, T-Lymphocyte/immunology/genetics ; Epitope Mapping ; Major Histocompatibility Complex ; *T-Cell Antigen Receptor Specificity/immunology ; Neoplasms/immunology ; *Immunity, Cellular ; },
abstract = {The discovery of MHC restriction, the resolution of peptide-MHC structure, and the identification of the T cell receptor gene quickly centered epitope-level specificity as a core concern of T cell biology. Epitope mapping culminated in functional peptide-based stimulation assays and tetramer staining, which together provide exquisite resolution of individual responses. Despite these tools, quantitative assessment of epitope-resolved responses in complex human infections and tumors has rarely been applied at scale. As a result, no epitope-aware correlates of protection or risk have been established for major infections, and most human T cell profiling still occurs at the level of representative epitopes or bulk assays. In this review, I propose that variation in specificity, defined as distinct epitope-level responses across individuals, represents a largely untested critical element in our assessment of anti-pathogen and antitumor immunity. Advances in TCR repertoire profiling and reverse epitope discovery now make formal tests of this hypothesis tractable, and I discuss approaches to determine the extent to which epitope variation underlies the noise and variation of human immune phenotypes.},
}

Humans
Animals
*T-Lymphocytes/immunology/metabolism
Receptors, Antigen, T-Cell/metabolism/genetics
*Epitopes, T-Lymphocyte/immunology/genetics
Epitope Mapping
Major Histocompatibility Complex
*T-Cell Antigen Receptor Specificity/immunology
Neoplasms/immunology
*Immunity, Cellular

@article {pmid42841375,
year = {2026},
author = {Pu, KS and Fernández-Viña, N and Martin-Villa, BC and Ramirez, D and Lewinsohn, RM and Smith, M and Boynton, H and Schapira, L and Smith, SM},
title = {"We Cannot Talk as a Family": Complexities of Survivorship Communication Among Hispanic/Latino Young Adult Survivors of Childhood Cancer, Parents, and Clinicians.},
journal = {Pediatric blood & cancer},
volume = {},
number = {},
pages = {e70739},
doi = {10.1002/1545-5017.70739},
pmid = {42841375},
issn = {1545-5017},
support = {K08 CA285829/CA/NCI NIH HHS/United States ; //Conquer Cancer-Janssen Research & Development/ ; //Stanford Pediatrics Residency Program/ ; /NH/NIH HHS/United States ; //LLC Career Development Award in Health Equity/ ; K08CA285829/CA/NCI NIH HHS/United States ; },
abstract = {BACKGROUND: Young adult childhood cancer survivors (YA-CCS) have an increased risk of treatment-related health complications throughout their lives. Lifelong survivorship care is recommended, yet many YA-CCS experience disruptions in care during pediatric-to-adult transitions and do not receive recommended survivorship care. Effective communication among YA-CCS, parents, and clinicians is essential for YA-CCS to understand their cancer history and survivorship care needs. However, families who use languages other than English, including Hispanic/Latino (H/L) families, often face barriers to effective communication and experience lower quality of care. With the long-term goal of improving communication and health outcomes, this study aimed to characterize communication related to survivorship care among H/L YA-CCS, their parents, and clinicians.

PROCEDURE: We conducted individual and small-group interviews with H/L YA-CCS (age 18-25, ≥5 years post-cancer diagnosis) and parents of YA-CCS to describe their experiences with posttreatment cancer-related communication, inside and outside the clinic. We analyzed qualitative data with applied thematic analysis.

RESULTS: Twenty YA-CCS and 18 parents participated at a median of 10 years post-diagnosis. Our results identified factors that influence cancer-related communication including family dynamics, language preferences, past experiences, and enduring emotional responses, which in turn shape YA-CCS' attitudes and beliefs about health risks.

CONCLUSIONS: In this study of H/L YA-CCS and parents, we observed a diverse range of communication preferences among participants. To promote more effective survivorship care, clinical communication should be tailored based on each family's informational needs, familial communication dynamics, language preferences, and attitudes toward survivorship health risks.},
}

@article {pmid42842684,
year = {2026},
author = {Chang, CH and A de la Cruz, AF and Lai, HY and Mejia Natividad, I and Noyola, A and Angelo Magsino Abellanosa, E and Lee, ND and Malik, HS},
title = {Rapid protamine evolution suppresses meiotic drive in Drosophila.},
journal = {Science advances},
volume = {12},
number = {41},
pages = {eaeb5514},
pmid = {42842684},
issn = {2375-2548},
support = {P40 OD018537/OD/NIH HHS/United States ; R01 GM074108/GM/NIGMS NIH HHS/United States ; U41 HG000739/HG/NHGRI NIH HHS/United States ; },
mesh = {Animals ; *Meiosis/genetics ; Male ; *Protamines/genetics/metabolism ; *Drosophila melanogaster/genetics ; *Drosophila Proteins/genetics/metabolism ; *Evolution, Molecular ; X Chromosome/genetics ; Female ; Spermatogenesis/genetics ; Fertility/genetics ; Spermatozoa/metabolism ; Sex Ratio ; Histones ; },
abstract = {Many animal species replace histones with protamines during spermatogenesis. Although essential for sperm function, protamines evolve rapidly for reasons that remain unknown. Using in vivo gene replacement, we examined the causes and consequences of the rapid evolution of Mst77F, a protamine essential for male fertility in Drosophila melanogaster (D. melanogaster). Replacing Mst77F with divergent orthologs caused DNA compaction defects in X-bearing sperm, resulting in fewer mature X-bearing sperm and male-biased progeny. Reducing D. melanogaster Mst77F dosage caused the same bias, whereas increasing the dosage of Mst77F orthologs rescued it. Engineered sex chromosome fusions revealed that Mst77F protects the D. melanogaster X chromosome from a killer-target meiotic drive system in a dosage- and sequence-dependent manner. Unlike in D. melanogaster, Mst77F was dispensable for fertility in Drosophila yakuba (D. yakuba) but remained important for suppressing sex ratio distortion. Our findings show that relentless pressure to suppress sex chromosome meiotic drive underlies the rapid evolution of protamines.},
}

Animals
*Meiosis/genetics
Male
*Protamines/genetics/metabolism
*Drosophila melanogaster/genetics
*Drosophila Proteins/genetics/metabolism
*Evolution, Molecular
X Chromosome/genetics
Female
Spermatogenesis/genetics
Fertility/genetics
Spermatozoa/metabolism
Sex Ratio
Histones

@article {pmid42842867,
year = {2026},
author = {Woodcock, J and Pierce, AJ and Drescher, CW and Leib, JR and Jafri, MS and Rader, DJ and Schreier, J and Ramage, J and Ramsey, SD and Dumanois, R and Davar, D and Mihajlovic, A and Giani, AM and Musa, FB and Montano-Campos, JF and Orr, MCM and Anderson Brooks, M and Emery, L and Powell, SS and Sholler, GS and Schadt, E and Paulovich, AG},
title = {Strengthening Individual-Patient Treatment Prediction in Precision Oncology: The Case for a National Evidence Infrastructure.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2600797},
doi = {10.1200/JCO-26-00797},
pmid = {42842867},
issn = {1527-7755},
}

@article {pmid42837156,
year = {2026},
author = {Yabroff, KR and Noone, AM and Mariotto, A and Shankaran, V and Ward, KC and Schwartz, SM and Wu, XC and Warren, JL},
title = {Court-Documented Adverse Financial Events Before Cancer Diagnosis and Mortality Risk.},
journal = {JAMA network open},
volume = {9},
number = {10},
pages = {e2637677},
pmid = {42837156},
issn = {2574-3805},
}

@article {pmid42837634,
year = {2026},
author = {Shih, L and Arnold, KB and Bansal, A and Bell-Brown, A and Watabayashi, K and Hershman, DL and Ramsey, SD},
title = {Impact of Primary Prophylactic Colony-Stimulating Factor Delivery Method on Febrile Neutropenia: Secondary Analysis of a Pragmatic Cluster Randomized Clinical Trial.},
journal = {JCO oncology practice},
volume = {},
number = {},
pages = {OP2600296},
pmid = {42837634},
issn = {2688-1535},
support = {T32 CA009515/CA/NCI NIH HHS/United States ; U10 CA180819/CA/NCI NIH HHS/United States ; UG1 CA189974/CA/NCI NIH HHS/United States ; },
abstract = {PURPOSE: Primary prophylactic colony-stimulating factor (PP-CSF) is recommended for patients receiving chemotherapy with high risk of febrile neutropenia (FN). The impact of PP-CSF delivery method on FN is unknown. We performed a secondary analysis of SWOG S1415CD (Trial Assessing CSF Prescribing Effectiveness and Risk), a pragmatic, cluster-randomized trial evaluating a guideline-informed standing order system to improve PP-CSF use, to evaluate associations between PP-CSF delivery method and FN.

METHODS: Female patients with breast cancer receiving first-line chemotherapy and PP-CSF with a known delivery method (administration in-clinic [IC], home delivery via an on-body device [OBD], or home self-injection [SI]) were included. The primary outcome was FN within 6 months of chemotherapy initiation, defined per the Common Terminology Criteria for Adverse Events.

RESULTS: Among 1,713 patients, the median age was 55 years (IQR, 46-64). By stage, 566 (33%) were local, 709 (41%) regional, 41 (2%) distant, and 397 (23%) unknown. PP-CSF was delivered IC in 773 (45%), OBD in 862 (50%), and SI in 78 (5%). Most received high-risk FN regimens. Pegfilgrastim use was nearly exclusive in IC and OBD (98% and 99%), versus 29% in SI. FN incidence was low: IC 3.8% (95% CI, 2.5 to 5.3), OBD 5.0% (95% CI, 3.6 to 6.6), and SI 6.4% (95% CI, 2.1 to 14.3; P = .29). FN was associated with high-risk FN regimens (odds ratio [OR], 2.97 [95% CI, 1.2 to 9.9]; P = .04) and Zubrod performance status ≥2 (OR, 4.99 [95% CI, 1.12 to 15.9]; P = .01), but not with delivery method or PP-CSF agent.

CONCLUSION: Women with breast cancer receiving chemotherapy and PP-CSF had low rates of FN regardless of PP-CSF delivery method or agent. Delivery decisions may be guided by patient-centered factors including cost, convenience, and access.},
}

@article {pmid42837666,
year = {2026},
author = {Bajaj, P and Abelman, DD and Luo, P and Ceccarelli, M and Schatz, JH and Watson, DC and Baker, CN and Amidei, A and Warren, EH and Diamond, BT and Lesokhin, AM and Korde, NS and Shah, UA and Mailankody, S and Hassoun, H and Smith, EL and Kazandjian, D and Gnjatic, S and Pugh, TJ and Green, DJ and Landgren, O and Coffey, DG},
title = {Chromatin-informed cell-free DNA approach for detection of clinically measurable disease in multiple myeloma.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2026022335},
pmid = {42837666},
issn = {2473-9537},
abstract = {Multiple myeloma (MM) is monitored using bone marrow-based minimal residual disease (MRD) assays, which provide high sensitivity but require repeated invasive sampling and are limited to a single anatomical site. Cell-free DNA (cfDNA) offers a minimally invasive alternative, yet most cfDNA approaches rely on prior tumor profiling to identify patient-specific genomic alterations for subsequent tracking in plasma. Here, we developed MATADOR, a myeloma-specific, tumor-agnostic framework that leverages cfDNA fragmentation patterns at a fixed set of myeloma-specific chromatin-accessible regulatory regions. These regions were defined using single-nucleus ATAC-seq data from an independent MM cohort and used to quantify plasma cfDNA fragmentation at these loci without patient-specific tumor profiling. Using these locus-specific features alone, MATADOR distinguished clinically measurable from unmeasurable disease in a held-out test set with an area under the receiver operating characteristic curve (AUROC) of 0.94. These findings establish chromatin-informed cfDNA fragmentomics as a minimally invasive approach for disease assessment in MM without individualized tumor profiling, enabling blood-based assessment of disease beyond the constraints of bone marrow sampling.},
}

@article {pmid42839961,
year = {2025},
author = {Henikoff, S and Dent, SYR and Mostoslavsky, R and Wang, T and Comai, L},
title = {Editorial: Current insights in Epigenetics and Epigenomics.},
journal = {Frontiers in epigenetics and epigenomics},
volume = {3},
number = {},
pages = {1566501},
pmid = {42839961},
issn = {2813-706X},
support = {R01 CA279173/CA/NCI NIH HHS/United States ; },
}

@article {pmid42839978,
year = {2025},
author = {Henikoff, S and Ahmad, K},
title = {Hansemann's anaplastic theory of cancer after 135 years.},
journal = {Frontiers in epigenetics and epigenomics},
volume = {3},
number = {},
pages = {1607433},
pmid = {42839978},
issn = {2813-706X},
abstract = {The term "anaplasia" was coined in 1890 to describe chromosomal changes common to primordial cancer cells, but ever since the mechanisms whereby a cell becomes anaplastic has been the subject of much speculation. Recent results based on genomic and epigenomic profiles of cancer patient samples provide a glimpse into early events that lead to aneuploidy, the original defining feature of an anaplastic cell. We propose that the anaplastic cell is one in which RNA Polymerase II hypertranscribes S-phase-dependent histone genes, and the resulting histone excess facilitates DNA replication while competing for CENP-A, causing centromere breaks that initiate whole-arm aneuploidy.},
}

@article {pmid42840153,
year = {2026},
author = {Gasperetti, T and Kandhavelu, J and Jayatilake, M and Kanholm, T and Wang, S and Bansal, S and Low, SWY and Fish, BL and Omari, E and Araujo, YS and Chaurasia, SS and Argento, D and Stewart, RD and Cheema, AK and Boerma, M and Himburg, HA},
title = {Corrigendum to "Multi-organ acute and delayed effects following exposure to neutron radiation" [iScience 29 (2026) 116380].},
journal = {iScience},
volume = {29},
number = {10},
pages = {117641},
doi = {10.1016/j.isci.2026.117641},
pmid = {42840153},
issn = {2589-0042},
abstract = {[This corrects the article DOI: 10.1016/j.isci.2026.116380.].},
}

@article {pmid42818493,
year = {2026},
author = {Varnum-Finney, B and Heck, A and Srivatsan, S and Dozono, S and Wellington, R and Chankhunthod, A and Nourigat-McKay, C and Dignum, T and Trapnell, C and Hadland, B},
title = {Multiplexed single cell transcriptomics optimizes mesodermal patterning and hemogenic endothelial output from murine embryonic stem cells.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {42818493},
issn = {2693-5015},
abstract = {BACKGROUND: Early patterning of mesodermal precursor populations is a key step of hematopoietic development in the embryo. To better understand this process, we employed sci-Plex, a high-throughput method of measuring multiplexed perturbations at the single-cell level, to evaluate the transcriptional response of mouse embryonic stem cells subjected to a gradient of two key morphogens in early mesoderm/hematopoietic development, Activin and BMP4.

RESULTS: sci-Plex revealed varying combinations of Activin and BMP4 temporally influenced mesoderm patterning in vitro and subsequent production of cell types reflecting their in vivo counterparts. We leveraged sci-Plex data to further optimize the generation of intraembryonic-like hemogenic endothelial cells that serve as the precursors of definitive hematopoietic lineages, including hematopoietic stem cells.

CONCLUSIONS: This study highlights the utility of sci-Plex to dissect how dose and temporal integration of interacting signal pathways determines cell fates and serves as a resource to analyze cell fate choices in early mesoderm patterning at single cell resolution.},
}

@article {pmid42832384,
year = {2026},
author = {Pilcher, WC and Tang, H and Ferguson, K and Foltz, SM and Michaud, ME and Satpathy, S and Shah, NN and Jin, Y and Ohlstrom, D and Bakhtiari, M and Acharya, CR and Consortium, IA and Gout, AM and Keats, J and Dhodapkar, MV and Avigan, DE and Vij, R and Kumar, SK and Cho, HJ and Vlachos, IS and Ding, L and Gnjatic, S and Cole, CE and Nooka, AK and Lonial, S and Carpten, J and Mulligan, G and Baughn, LB and Bhasin, M},
title = {African Genetic Similarity Is Associated with Reduced Inflammation and Enhanced Adaptive Immunity in Multiple Myeloma.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2026033999},
pmid = {42832384},
issn = {1528-0020},
abstract = {The bone marrow immune microenvironment (BMME) is a critical factor in multiple myeloma (MM) pathogenesis. Despite higher incidence of MM among self-identified African Americans, the relationship between African genetic similarity and the BMME remains unclear. We present the largest analysis to date assessing the impact of Ancestry on the BMME in myeloma (N=320, including 64 with ≥50% African genetic similarity, AFR-High) leveraging our recently generated Immune Atlas. AFR-High was associated with enrichment of late T-effector cells, driven by rare cytotoxic CD4[+] T cells, suggesting a distinct adaptive BMME. AFR-High exhibited expansion of late-differentiated adaptive NK cells with high cytotoxic GNLY and GZMH expression. AFR-High depicted reduced CD14[+] monocytes, increased CD16[+] non-classical monocytes, and expansion of macrophage-like monocyte populations with enrichment of metabolic adaptation, efferocytosis and phagocytic clearance programs, and immunoregulatory pathways. These findings reveal a shift from an innate inflammatory immune landscape toward adaptive cytotoxic and immunoregulatory remodeling associated with African genetic similarity in MM.},
}

@article {pmid42833596,
year = {2026},
author = {Walker, R and Dowty, JG and Pearlman, R and Latham, A and , and Jenkins, MA and Buchanan, DD},
title = {Cancer risks for first-degree relatives of people with double somatic DNA mismatch repair mutations.},
journal = {Gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.1053/j.gastro.2026.09.015},
pmid = {42833596},
issn = {1528-0012},
}

@article {pmid42834086,
year = {2026},
author = {Bhakuni, R and Lee, JH and Goff, P and Jones, D and Nguyen, L and Lin, R and Newell, EW and Garman, KA and Hall, ET and Gilad, O and Brownell, I and Brown, EJ and Nghiem, P},
title = {ATR inhibition induces NF-κB-dependent immunogenicity in Merkel cell carcinoma independent of cGAS-STING.},
journal = {NPJ precision oncology},
volume = {10},
number = {1},
pages = {},
pmid = {42834086},
issn = {2397-768X},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; P01 CA225517//NIH / NCI Research Program Project Grant/ ; P30 CA015704//NIH / NCI Cancer Center Support Grant/ ; P01 CA225517/CA/NCI NIH HHS/United States ; 22-003-AS//The Mark Foundation for Cancer Research/ ; #15CHAS04//Kelsey Dickson Team Science Courage Research Team Award/ ; },
abstract = {There is a major unmet need to develop therapies for patients whose tumors do not respond to PD-1 blockade. Inhibition of the ATR-mediated DNA replication checkpoint has been reported to augment antitumor immunity, although the underlying mechanisms remain poorly understood, particularly in cGAS-STING-deficient tumors. Here, we investigated the effects of ATR inhibition (ATRi) on tumor immunogenicity in Merkel cell carcinoma (MCC), an aggressive skin cancer commonly driven by Merkel cell polyomavirus (MCPyV). Among 92 primary MCC tumors, Ki-67 positivity was observed in 50% of MCPyV-positive and 83% of MCPyV-negative tumor cells, suggesting reliance on ATR-mediated replication stress responses. Notably, MCC frequently exhibits cGAS-STING deficiency, especially in MCPyV-positive tumors. In representative MCPyV-positive and -negative MCC cell lines, ATRi enhanced cytotoxicity and, alone or combined with low-dose radiation, induced proinflammatory NF-κB transcriptional programs. These included increased expression of MHC class I, antigen-processing machinery, interleukins, chemokines, and interferon-related genes. ATRi also increased surface calreticulin exposure and subsequent phagocytosis by human monocyte-derived macrophages. These findings support ATRi-mediated immune reprogramming in MCC cells through an NF-κB signaling cascade, regardless of cGAS-STING functional status. These observations support clinical evaluation of ATR inhibitors in immunotherapy-refractory disease (NCT05947500) and suggest candidate biomarkers of therapeutic response.},
}

@article {pmid42834094,
year = {2026},
author = {Gang, M and Gale, RP and Walter, RB},
title = {Recombinant hematopoietic growth factors in acute myeloid leukemia.},
journal = {Leukemia},
volume = {},
number = {},
pages = {},
pmid = {42834094},
issn = {1476-5551},
}

@article {pmid42836651,
year = {2026},
author = {Berkman, AM and Teachey, DT and Ehrhardt, MJ and Pui, CH and Inaba, H and Karol, SE and Castellino, SM and Dixon, SB and Yang, JJ and Gross, TG and Federico, SM and Packer, RJ and Pappo, AS and Qaddoumi, I and Salloum, R and Smith, SM and Cooper, T and Henderson, TO and Hawkins, DS and Nathan, PC and Chow, EJ and Fox, E and Armstrong, GT},
title = {Late effects after novel therapies for childhood cancer: Anticipating the future landscape of health outcomes for survivors.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djag371},
pmid = {42836651},
issn = {1460-2105},
abstract = {Five-year survival rates for childhood cancer now exceed 85%, with recent improvements driven by advances in understanding of tumor biology allowing for molecular risk stratification. The introduction of novel therapies, including antibodies, antibody-drug conjugates, immune checkpoint inhibitors, cellular therapy, and targeted small molecule inhibitors into early-phase and pivotal trials has the potential to further improve survival. Although these agents have transformed outcomes for some children with cancer, their long-term toxicity profiles remain poorly defined. Large cohort studies have characterized the late effects of conventional cytotoxic chemotherapies and radiation, informing survivorship guidelines and risk-based surveillance strategies. In contrast, the distinct mechanisms of action of targeted and immune-based therapies introduce new and potentially persistent toxicities affecting cardiovascular, neurologic, endocrine, gastrointestinal, and immune systems. This review synthesizes current evidence on acute toxicities of novel therapies and summarizes available data about persistent long-term toxicities and new onset late effects outcomes, including growth impairment, persistent immune dysfunction, and subsequent malignancies in children treated with these agents. We focus on therapies with U.S. Food and Drug Administration approval for pediatric indications. Current evidence from acute toxicity profiles, limited pediatric long-term follow-up, and emerging data from adult populations highlights the urgent need for systematic evaluation of long-term outcomes in children treated with these therapies. As the use of novel agents continues to expand, extending established survivorship cohorts to include children exposed to novel therapies, while developing complementary approaches to detect previously unrecognized toxicities, will be essential for defining late effects and informing evidence-based surveillance and intervention strategies.},
}

@article {pmid42327168,
year = {2026},
author = {Sokabe, M and Alvarado, C and Lapointe, CP and Villa, N and Puglisi, JD and Fraser, CS},
title = {A ribosomal kinetic checkpoint governs selective mRNA recruitment.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42327168},
issn = {2692-8205},
abstract = {Translation initiation begins with recruitment of mRNA to the ribosome, yet how mRNA engagement is converted into productive initiation remains unclear. Using real-time fluorescence assays with purified components, we show that mRNA recruitment proceeds through a branched kinetic pathway on the 40S subunit. Following rapid sampling, mRNAs partition into either a productive accommodated state or an arrested state that stabilizes ribosome binding before accommodation. mRNA structure, eIF3, and eIF3j bias recruitment toward arrest, whereas eIF4F promotes accommodation in an ATP-dependent manner coupled to displacement of eIF3j from the mRNA entry channel. Unstructured mRNAs accommodate independently of eIF4E, whereas structured mRNAs require an upstream eIF4E-dependent step, enabling selective recruitment under limiting eIF4E. Arrested complexes can convert directly into the accommodated state without dissociation, revealing a reversible standby intermediate poised for activation. Together, our findings establish mRNA accommodation as a ribosome-intrinsic checkpoint governing initiation and provide a framework for selective translation.},
}

@article {pmid42830144,
year = {2026},
author = {Benetton, M and Da Ros, A and Peloso, A and Longo, G and Perpinello, S and Frasson, C and Branco Fonseca, T and Varotto, E and Bresolin, S and Tregnago, C and Scorrano, L and Huang, BJ and Meshinchi, S and Locatelli, F and Pigazzi, M},
title = {Reactive oxygen species define leukemia stem cell identity in pediatric acute myeloid leukemia.},
journal = {Cancer letters},
volume = {},
number = {},
pages = {218866},
doi = {10.1016/j.canlet.2026.218866},
pmid = {42830144},
issn = {1872-7980},
abstract = {Standard chemotherapy effectively induces complete remission in most children with acute myeloid leukemia (AML), however relapse remains the main cause of treatment failure. Leukemia stem cells (LSCs) are proposed to constitute a therapy-resistant reservoir driving disease recurrence, but their reliable identification remains unresolved. We explored intracellular reactive oxygen species (ROS) levels in pediatric AML at diagnosis and sorted ROS-low (RL) and ROS-high (RH) cell fractions. We found that RL cells exhibited increased quiescence, sustained serial colony-forming capacity and engraftment in mice when compared to the RH fraction. Moreover, in a 3D niche model, RL cells preferentially localized to hypoxic regions and were resistant to cytarabine, altogether indicating enrichment for functional LSCs. Transcriptomic analyses revealed enrichment of stemness, adhesion and niche-interaction programs in RL cells, alongside downregulation of mitochondrial and oxidative phosphorylation pathways. Consistently, RL cells displayed reduced oxygen consumption and ATP production, together with remodeled cristae structure despite preserved mitochondrial mass. Paradoxically, complex I inhibition selectively impaired RL cell viability, indicating a dependency on oxidative phosphorylation. Using RL transcriptome, we derived a gene signature that, when applied to single-cell RNA-sequencing data of pediatric AML cases, identified LSCs within the bulk regardless of differentiation status, and showed significant prognostic value. Finally, transcriptional program trajectory indicated that RL fraction contributed to generate the whole AML bulk, whereas gene mutations were maintained in RL and RH cells. Overall, this ROS-based strategy represents a new tool to isolate stem cells transcending traditional markers, and identifies novel clinically relevant vulnerabilities to target LSCs.},
}

@article {pmid42831003,
year = {2026},
author = {Stone, D and Jerome, KR},
title = {Deceiving HIV: Engineered erythrocytes as cellular decoys.},
journal = {Molecular therapy. Advances},
volume = {34},
number = {4},
pages = {201849},
pmid = {42831003},
issn = {3117-387X},
}

@article {pmid42538935,
year = {2026},
author = {Dadonaite, B and Dosey, A and Ahn, JJ and Yu, TC and Sunshine, SA and Farrell, AG and King, NP and Bloom, JD},
title = {Defining the molecular interaction between influenza hemagglutinin and MHC-II.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42538935},
issn = {2692-8205},
abstract = {The hemagglutinin (HA) of some influenza viruses can interact with major histocompatibility complex class II (MHC-II), but how these proteins interact is unclear. Here we demonstrate that diverse H5 HAs can use MHC-II to enter cells, with avian MHC-II enabling more efficient entry than human MHC-II for most H5 HAs. To define the molecular interface, we use pseudovirus deep mutational scanning to measure how mutations to H5 HA affect its interaction with tufted duck MHC-II, and identify mutations that restrict HA to exclusively MHC-II or sialic acid receptors. We leverage identification of H5 HA mutations that increase binding to tufted duck MHC-II to determine a 4.8 Å cryo-EM model of the complex. To support the structural model, we measure how all mutations to tufted duck MHC-II affect its interaction with H5 HA, and find the alpha chain is the dominant determinant but beta chain sites near the peptide-binding groove also contribute. To generalize these findings, we use deep mutational scanning to show that a H7 HA interacts with MHC-II similarly to H5 HA. Finally, we show that H1, H2, H3, and H9 HAs interact with avian or human MHC-II, although interactions vary among strains that evolved in different hosts.},
}

@article {pmid42818230,
year = {2026},
author = {Niu, Y and Xu, Q and Mak, CY and Xu, Y and Parmar, A and Zevin, A and Khyzha, N and Paranal, R and Holland, E and Ahmad, K and Henikoff, S and Zheng, Y},
title = {FFPE-CUTAC: A Single Assay, Multiple Layers.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42818230},
issn = {2692-8205},
abstract = {BACKGROUND: Archival biobanks of formalin-fixed paraffin-embedded (FFPE) specimens represent a vast and underused resource for retrospective molecular studies linked to clinical follow-up. However, fixation-induced chemical modification and nucleic acid fragmentation limit scalable genomic and transcriptomic profiling. FFPE-CUTAC (Cleavage Under Targeted Accessible Chromatin) is an RNA polymerase II-targeted DNA assay specifically designed to profile regulatory activity in FFPE tissue. Here, we assess its archival robustness, information content, compatibility with RNA-seq, and ability to recover copy-number alterations.

RESULTS: In meningioma and breast cancer cohorts, we benchmarked FFPE-CUTAC against matched fresh-frozen RNA-seq, FFPE RNA-seq and FFPE whole-genome sequencing. For FFPE specimens spanning up to 25 years, FFPE-CUTAC showed no systematic collection-year-associated decline in library yield or signal-quality metrics. In contrast, FFPE RNA-seq is more affected by the FFPE tissue degradation and specimen age on read composition, gene-body coverage, and gene detection. By measuring RNA polymerase II occupancy on chromatin rather than mature RNA abundance, FFPE-CUTAC is less constrained by transcript half-life, polyadenylation or transcript-capture design. FFPE-CUTAC extends beyond gene regions to non-coding regulatory elements, while the shared gene-level signals supported its integration with existing RNA-seq cohorts for large-scale, long-term clinical association study. FFPE-CUTAC libraries also retain DNA dosage information and can be used to recover chromosome-arm gain, loss and intact states with 96% concordance to matched whole-genome sequencing.

CONCLUSIONS: By converting routinely preserved pathology sections into integrated regulatory and copy-number profiles, FFPE-CUTAC provides a practical foundation for constructing clinically annotated disease maps to support molecular stratification, prognostic modeling and treatment-association studies.},
}

@article {pmid42827221,
year = {2026},
author = {Grivas, P and Agarwal, PK and Al-Ahmadie, H and Friedlander, T and Geynisman, DM and Lotan, Y and Morgans, AK and Bianco, FJ and Chandana, S and Fang, B and Large, M and Meeks, JJ},
title = {Prevalence of PD-L1-High Tumor Expression and Association with First-Line Treatment Outcomes in Patients with Metastatic Urothelial Carcinoma: Results from a Prospective Observational Cohort Study.},
journal = {Targeted oncology},
volume = {},
number = {},
pages = {},
pmid = {42827221},
issn = {1776-260X},
abstract = {BACKGROUND: Programmed death-ligand 1 (PD-L1) expression has been studied extensively in clinical trials of metastatic urothelial carcinoma.

OBJECTIVE: We aimed to provide information on the prevalence of tumor PD-L1 expression and treatment outcomes in patients with metastatic urothelial carcinoma in a real-world setting.

METHODS: PREVAIL (NCT03788746) enrolled patients with metastatic urothelial carcinoma undergoing systemic first-line treatment at US community oncology practices. The primary endpoint was the prevalence of pretreatment tumor PD-L1-high expression using an immunohistochemistry antibody for PD-L1 (SP263) [Roche Diagnostics]. Secondary endpoints included treatment patterns and association between PD-L1 expression and objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).

RESULTS: Among 139 patients, the pretreatment prevalence of PD-L1-high expression was 53.2% (95% confidence interval 44.6-61.7). Forty-seven patients (33.8%) received anti-PD-L1/anti-programmed death 1 agents alone as first-line therapy. In all evaluable patients, ORR was 50.9%, median PFS was 15.1 months, and median OS was 25.4 months from the first dose of first-line therapy. There was no significant difference in PFS (hazard ratio 0.72; 95% confidence interval 0.34-1.52; p = 0.385) or OS (hazard ratio 0.71; 95% confidence interval 0.44-1.15; p = 0.164) in patients with pretreatment PD-L1-high versus PD-L1-low expression. Objective response rate was similar between patients with PD-L1-high (17/33; 51.5%) and PD-L1-low (12/24; 50.0%) expression.

CONCLUSIONS: In this observational study, more than half of patients had high pretreatment tumor PD-L1 expression. There was no significant association between PD-L1 status and ORR, PFS, or OS with any first-line therapy, although definitive conclusions cannot be made because of the limited sample size.},
}

@article {pmid42827867,
year = {2026},
author = {Shahamati, D and Yang, B and Liu, S and Odegaard, AO and Allison, M and Glenn, AJ and Jung, SY and Nudy, M and Schnatz, PF and Shadyab, AH and Shikany, JM and Tinker, LF and Wallace, RB and Wang, Y and Landry, MJ},
title = {Association between the planetary health diet index and risk of cardiovascular diseases in postmenopausal women: Findings from the Women's Health Initiative Observational Study.},
journal = {American journal of preventive cardiology},
volume = {30},
number = {},
pages = {101750},
pmid = {42827867},
issn = {2666-6677},
}

@article {pmid42326801,
year = {2026},
author = {Li, Q and Xu, L and Wang, J and Li, C and Wen, W and Shu, X and Yang, Y and Shu, XO and Cai, Q and Long, J and Singh, B and Lau, KS and Yin, Z and Casey, G and Song, M and Peters, U and Zheng, W and Guo, X},
title = {Deconvolution-based cell-type specific DNA methylation-wide and transcriptome-wide association studies identify risk CpG sites and genes associated with colorectal cancer risk.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {42326801},
abstract = {Bulk tissue-based DNA methylation-wide (MWAS) and transcriptome-wide association studies (TWAS) have identified CpG sites and genes associated with colorectal cancer (CRC) risk, but do not account for cellular heterogeneity. To address this, we developed a deconvolution-informed framework to infer cell-type specific DNA methylation and gene expression profiles from bulk normal colon tissues using reference single-cell epigenomic and transcriptomic datasets. We performed cell-type specific MWAS (ctMWAS) using deconvoluted DNA methylation data from 293 normal colon samples and conducted cell-type specific TWAS (ctTWAS) using deconvoluted gene expression data from 707 normal colon samples. Genetically predicted methylation and expression models were integrated with CRC GWAS summary statistics (78,473 cases and 107,143 controls) to identify risk-associated CpG sites and genes. Through ctMWAS, ctTWAS, and colocalization analyses, we identified 178 high-confidence cell-type-specific CpG sites and 68 genes associated with CRC across 26 previously unreported GWAS loci. Through additional integrative methylation-gene analysis, we prioritized 132 candidate risk genes, the majority of which were supported by multi-omics evidence and stage-specific dysregulation across the adenoma-carcinoma and serrated-carcinoma progression pathways. Pathway enrichment analyses implicated pathways involved in DNA double-strand break repair, TP53 regulation, TGF-β signaling, and innate immune responses. Among prioritized genes, 14 were identified as putative druggable targets linked to 90 FDA-approved or clinical-stage drugs. Experimental validation supports an oncogenic role for SF3A3. These findings demonstrate that deconvolution-informed integrative analyses enable cell-type-resolved identification of epigenetic and transcriptional mechanisms underlying CRC susceptibility and provide insights into disease biology, prevention, and therapeutic target discovery.},
}

@article {pmid42817947,
year = {2026},
author = {Oshiro, RT and Pratt, AA and Dunham, DT and Doyle, LA and Gill, C and Chouldjian, A and Higashi, KM and Acosta, JP and McGuire, SF and Nouwens, S and Kaiser, BK and Seed, KD},
title = {Surviving phage attack primes bacterial immunity to defeat counterdefenses.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42817947},
issn = {2692-8205},
abstract = {Transcriptional repressors with ligand-responsive WYL domains control diverse bacterial defense systems, yet the natural cues driving derepression and the physiological rationale for dynamic regulation in native host-phage contexts remain unknown. Here, we show that restricted phage infection, where defense clears a primary attack, serves as a natural cue for WYL-mediated derepression in Vibrio cholerae. Although not required to block the initial infection, this response increases defense protein abundance, shifting host-phage stoichiometry and priming surviving bacteria to overwhelm phage-encoded counterdefenses in subsequent attacks. We also find that restricted infection co-induces an unlinked anti-plasmid defense via its own WYL repressor, showing that parallel WYL sensors coordinate a broader immune response without regulatory crosstalk. In contrast, productive phage infection triggers horizontal transfer of the defense-encoding mobile element, ensuring its persistence in the population. Together, our work reveals that infection fate dictates divergent outcomes for the expression and dissemination of bacterial immunity.},
}

@article {pmid42818208,
year = {2026},
author = {Stoddard, CI and Litchford, ML and Sung, K and Hutcheson, RL and Marceau, J and Johnson, T and Ota, A and Baumgarten, NE and Gale, M and Overbaugh, J},
title = {A knockout screening platform for interferon-stimulated genes in respiratory cells identifies LY6E as a dominant antiviral effector against coronaviruses.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42818208},
issn = {2692-8205},
abstract = {Human coronaviruses (HCoVs) cause pathogenic outcomes ranging from mild illness to severe respiratory disease. Determining how respiratory cells coordinate an early antiviral response is necessary to understand successful control of HCoV replication. The Type I Interferon (IFN) response is a major component of innate viral immunity. IFN signaling leads to the upregulation of hundreds of interferon-stimulated genes (ISGs) that can have antiviral activity, though the individual ISGs that are responsible for restricting mildly pathogenic HCoVs in the respiratory epithelium are not clear. Here, we developed a targeted CRISPR-Cas9 knockout sgRNA library (termed the respISG library), focusing on ISGs that are upregulated across a panel of respiratory cells, to screen for innate host factors that restrict the mildly pathogenic human coronavirus, HCoV-OC43. We executed cell death-based screens in immortalized human small airway epithelial cells and identified lymphocyte antigen 6E (LY6E) as a top hit. We confirmed LY6E activity in validation studies and found it regulates entry of various SARS-CoV-2 Spike-pseudotyped lentiviruses. In addition to demonstrating a key role for LY6E in blocking a variety of HCoVs in small airway epithelial cells, this study establishes a loss-of-function CRISPR-Cas9 screening platform for identification of HCoV antiviral ISGs in respiratory cells.},
}

@article {pmid42818447,
year = {2026},
author = {Suger, AH and Harrison, TA and Haas, CB and Chen, H and Fan, S and Bolla, MK and Wang, Q and Dennis, J and Michailidou, K and Dunning, AM and Easton, DF and Southey, MC and Fasching, PA and Haeberle, L and Stone, J and Gago-Dominguez, M and Castelao, JE and Aronson, K and Murphy, RA and Evans, DG and Loi, S and , and Couch, FJ and Yadav, S and Milne, RL and Haiman, CA and Scott, CG and Norman, A and John, EM and Mulligan, AM and Kristensen, VN and Eliassen, AH and Andrulis, IL and Figueroa, JD and Astley, S and Czene, K and Pharoah, PDP and Antoniou, AC and García-Closas, M and Berrington, A and Gierach, GL and Vachon, CM and Tamimi, RM and Lindström, S},
title = {Circulating Inflammatory Markers and Mammographic Density Phenotypes: a Mendelian Randomization Analysis.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {42818447},
abstract = {Observational studies have identified associations between circulating inflammatory markers (CIMs) and mammographic density (MD) phenotypes, but whether these associations reflect causal effects remains unclear. We utilized two-sample Mendelian randomization (MR) to assess relationships between 60 CIMs and MD phenotypes in individuals of European genetic ancestry by examining associations between genetically predicted CIM concentrations and three MD phenotypes (dense area, DA: N = 13,965; non-dense area, NDA: N = 14,036; percent density, PMD: N = 17,841). Primary analyses were conducted using the inverse variance weighted MR method. No CIM-MD phenotype associations reached statistical significance after correction for multiple testing. At a nominal significance level of p < 0.05, we observed suggestive evidence for eight associations represented by six unique CIMs (MD phenotype/direction of association): CCL23 (DA/+), CD40 (NDA/-), GDNF (DA/+ & PMD/+), MMP-10 (DA/+ & PMD/+), TRANCE (DA/-), and TWEAK (NDA/+). In multivariable MR analyses accounting for body mass index (BMI), we observed six nominal associations represented by six unique CIMs, although most instruments demonstrated weak conditional instrument strength after inclusion of BMI. Overall, our comprehensive analysis of 60 CIMs provides limited evidence supporting broad causal effects of circulating inflammatory markers contributing to variation in MD phenotypes.},
}

@article {pmid42822323,
year = {2026},
author = {Habel, JR and Nguyen, THO and Allen, LF and Skinner, MJ and Kedzierski, L and Allen, EK and Li, S and de Alwis, N and Hagen, RR and Doggett, K and Jia, X and Tarasova, I and Minervina, AA and Pogorelyy, MV and Holloway, AI and Mathew, NL and Saunders, PM and Clatch, A and Evrard, M and Xu, C and Koay, HF and Abdullah-Al-Kamran Khan, M and Mackay, LK and Barrow, AD and Douros, C and Karapanagiotidis, T and Nicholson, S and Bond, K and Williamson, DA and Hui, L and Lappas, M and Walker, S and Nicholson, SE and Hannan, NJ and Brooks, AG and Schroeder, J and Crawford, JC and Thomas, PG and Rowntree, LC and Kedzierska, K},
title = {Multidimensional molecular profiling reveals decidual and circulating NK cell dynamics in early and late pregnancy.},
journal = {EBioMedicine},
volume = {132},
number = {},
pages = {106495},
doi = {10.1016/j.ebiom.2026.106495},
pmid = {42822323},
issn = {2352-3964},
abstract = {BACKGROUND: Human pregnancy presents a unique physiological state that allows for growth of an antigenically dissimilar foetus. The immune system plays a key role in establishing and maintaining successful pregnancy, yet detailed understanding of immunological responses in pregnancy is lacking.

METHODS: We defined the immunological landscape in pregnancy by screening >350 markers on NK cells, CD4[+], CD8[+] and γδ T cells, B cells and monocytes in third-trimester pregnancy peripheral blood, cord blood and decidua, and by performing single-cell RNA sequencing (scRNAseq), including 130 CITE-seq antibodies, on NK cells from the blood and decidua of third-trimester pregnancies. We validated our findings in additional blood and decidua samples from first- and third-trimester pregnancies. Blood samples from non-pregnant women were used as a control group for comparison.

FINDINGS: Our multiomic approaches revealed altered surface proteomes in lymphoid and myeloid immune subsets during third-trimester pregnancy, in comparison to non-pregnant women. In the blood during pregnancy, circulating NK cells displayed increased SOCS1 (FDR < 0.001) and AREG (FDR < 0.001), both involved in tightly regulating immune responses, as well as HLA-D family (FDR < 0.05-0.0001) gene expression, with increased CCR5 (p < 0.01-0.001) and HLA-DR (p < 0.01-0.001), and decreased CD9 (p < 0.001), CD36 (p < 0.05-0.001), and CX3CR1 (p < 0.05) at the protein level, validated in samples from first- and third-trimester pregnancies. Our analysis of decidual NK (dNK) cells demonstrated a decline in the dNK1 subset between first-trimester decidua and third-trimester decidua basalis (p < 0.0001) and parietalis (p < 0.01), and identified an adaptive-like subset with high expression of cytotoxic molecules, which could be distinguished from the previously described dNK1-3 subsets and was enriched in decidua from women with a history of cytomegalovirus infection (p < 0.05). Functionally, we observed enhanced control of IFN-γ secretion in response to proinflammatory IL-12/IL-18 cytokines in pregnancy (p < 0.05-0.01), however induction of SOCS1 protein expression remained similar between pregnant and non-pregnant women.

INTERPRETATION: Overall, our study provides key insights into immunity in pregnancy and reveals fundamental differences in the NK cell compartment. Understanding pregnancy-specific immunology fills important knowledge gaps to better inform the rational design of vaccines, immunotherapies and identification of biomarkers for safe pregnancy outcomes.

FUNDING: Australian National Health and Medical Research Council, Australian Medical Research Future Fund, and the National Institute of Allergy and Infectious Diseases.},
}

@article {pmid42822618,
year = {2026},
author = {Kelly, JJ and Chen, Z and Thalji, N and Zhang, B and Zhao, Y and Patrick, WL and Goel, NJ and Brown, CR and Lawrence, KM and Szeto, WY and Bavaria, JE and Desai, ND},
title = {Surgery for Acute Type A Aortic Dissection on Preoperative Anticoagulants and Antiplatelet Agents.},
journal = {The Annals of thoracic surgery},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.athoracsur.2026.08.029},
pmid = {42822618},
issn = {1552-6259},
abstract = {BACKGROUND: Patients taking direct oral anticoagulants (DOACs), warfarin, or dual antiplatelet therapy (DAPT) who present with acute Type A aortic dissection (ATAAD) are a unique challenge. Our objective was to investigate the surgical outcomes of this patient population.

METHODS: A retrospective cohort study was performed of 20,530 patients who underwent first-time sternotomy repair of ATAAD in the Society of Thoracic Surgeons Adult Cardiac Surgery Database from 2017 to 2022. Propensity score matching was used to pair each DOAC (n=625), warfarin (n=245), and DAPT (n=525) patient with 2 controls. Outcomes included operative mortality and reoperation for bleeding.

RESULTS: Compared to matched controls, mortality was higher for patients on DOACs (24.8% vs 17.9%, OR 1.50 [1.2,2.0], p<0.001), warfarin (26.7% vs 19.2%, OR 1.6 [1.1,2.4], p=0.02), or DAPT (27.4% vs 20.1%, OR 1.5 [1.2,2.0], p=0.001). Reoperation for bleeding was higher for DOACs (12.0% vs 7.0%, OR 1.8 [1.3,2.5], p=0.001) and DAPT (15.2% vs 7.3%, OR 2.2 [1.6,3.2], p<0.001), and trended that way for warfarin (11.4% vs 7.8%, OR 1.5 [0.9,2.6], p=0.11). Most DOAC (76.5% [478/625]) and DAPT (71.2% [374/525]) patients underwent surgery on the day of admission. While there was a non-significant difference toward lower mortality for DOAC patients who had surgery on day ≥1 (17.4% vs 25.0%, p=0.08), there was no difference for those on DAPT.

CONCLUSIONS: Patients undergoing first-time surgery for ATAAD on DOACs, DAPT, or warfarin preoperatively had increased mortality and bleeding complications. For those on DOACs or DAPT, further study is required to investigate whether delaying surgery impacts outcomes.},
}

@article {pmid42822697,
year = {2026},
author = {Brown, AD and Frongillo, EA and Flory, K and Lohman, M and Krobath, D and Julceus, EF and Wei, J and Reboussin, BA and Mendoza, JA and Bellatorre, A and Malik, F and Liese, AD},
title = {Discrimination and material-need insecurities intersect in association with poor mental health among youth and young adults with type 1 diabetes.},
journal = {Canadian journal of diabetes},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jcjd.2026.09.006},
pmid = {42822697},
issn = {2352-3840},
abstract = {OBJECTIVE: Little is known about how perceived discrimination and material-need insecurities jointly contribute to poor mental health among youth and young adults (YYA) with diabetes. We examined how these factors intersect to influence mental health among YYA with type 1 diabetes.

METHOD: Analyses included 829 YYA with type 1 diabetes from the SEARCH Food Security Cohort study. Classification tree analysis identified patterns among perceived discrimination, material-need insecurities, demographic, and socioeconomic characteristics that distinguish between moderate-to-severe and minimal-to-mild depressive and anxiety symptoms assessed using the Center for Epidemiological Studies-Depression and the 7-item Generalized Anxiety Disorder scales. Material-need insecurities included household food insecurity, housing, and transportation insecurity.

RESULTS: Overall, 35.6% of participants reported moderate-to-severe depressive symptoms and 27.6% reported moderate-to-severe anxiety symptoms. Discrimination intersected with food insecurity among YYA with type 1 diabetes such that 86% of those experiencing greater discrimination and food insecurity reported moderate-to-severe depressive symptoms compared to 47% among the food secure group. In those reporting less discrimination, 56% of those with food insecurity reported moderate to severe depressive symptoms compared to 17% among the food secure group. For anxiety, 56% of those with food insecurity reported moderate-to-severe symptoms among those who were food secure, 40.4% of those with greater discrimination and 16.8% of those with less discrimination reported moderate-to-severe anxiety symptoms. Adding discrimination to models which included food insecurity and demographic measures improved prediction accuracy (AUC=0.71 versus AUC=0.64 for depressive and AUC=0.68 versus AUC=0.64 for anxiety symptoms).

CONCLUSIONS: Addressing household food insecurity and discrimination may help to decrease mental health problems among YYA with type 1 diabetes.},
}

@article {pmid42823219,
year = {2026},
author = {Gulati, R and Etzioni, R},
title = {Re: Stockholm3 Versus Prostate-specific Antigen in Prostate Cancer Screening: 9 yr 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.2026.09.015},
pmid = {42823219},
issn = {1873-7560},
}

@article {pmid42826055,
year = {2026},
author = {Shen, BA and Asfahl, KL and Lim, B and Bertolli, SK and Minot, SS and Radey, MC and Penewit, KM and Ngo, B and Salipante, SJ and Johnston, CD and Peterson, SB and Goodman, AL and Mougous, JD},
title = {The type VI secretion system governs strain maintenance in a wild mammalian gut microbiome.},
journal = {eLife},
volume = {15},
number = {},
pages = {},
pmid = {42826055},
issn = {2050-084X},
support = {R35GM118159/NH/NIH HHS/United States ; R35 GM118159/GM/NIGMS NIH HHS/United States ; R01 DE027850/DE/NIDCR NIH HHS/United States ; F32 AI164853/AI/NIAID NIH HHS/United States ; DE027850/NH/NIH HHS/United States ; F32 AI164853/NH/NIH HHS/United States ; },
mesh = {Animals ; *Type VI Secretion Systems/metabolism/genetics ; Mice ; *Gastrointestinal Microbiome ; *Bacteroides/genetics/metabolism/growth & development ; },
abstract = {Bacteria inhabiting the mammalian gut coexist in dense communities where contact-dependent antagonism mechanisms are widespread. The type VI secretion system (T6SS) is an interbacterial toxin delivery pathway prevalent among gut Bacteroidales, yet its function in naturally evolved microbiomes remains poorly defined. Here, we examine the role of the T6SS in Bacteroides within a physiologically relevant gut community derived from wild mice (the WildR microbiome). Using newly developed genetic tools and a strategy for functional replacement of strains within the WildR community, we demonstrate that the WildR isolate B. acidifaciens employs a T6SS to antagonize co-resident Bacteroidales. We also show that loss of T6SS function compromises the long-term maintenance of B. acidifaciens in the community but not its initial colonization, establishing the system as a determinant of strain persistence. The T6SS we identified resides on an integrative and conjugative element (ICE). ICE-seq, a targeted sequencing approach, reveals that the T6SS-ICE is distributed among select Bacteroidales and Muribaculaceae species in the WildR microbiome, between which it appears to be recently exchanged. We also show that transfer of the T6SS-ICE to WildR isolate Phocaeicola vulgatus confers transient colonization benefits in mice, but is linked to eventual population decline. Our findings demonstrate that the T6SS can stabilize the presence of specific strains within a complex, co-evolved gut microbiome, yet its value is context dependent and constrained by the ecological and physiological landscape of the host community.},
}

Animals
*Type VI Secretion Systems/metabolism/genetics
Mice
*Gastrointestinal Microbiome
*Bacteroides/genetics/metabolism/growth & development

@article {pmid42327314,
year = {2026},
author = {Kanaan, SB and McDonough, A and Gentil, C and Ojemann, J and Heaton, H and Behboudi, R and Eisenberg, DTA and Furlan, SN and Geraghty, D and Rutledge, J and Urselli, F and Weinstein, JR and Nelson, JL},
title = {Microchimerism in the Human Brain, Quantitative Assessment and Single Nuclei Profiling Establish Cell Types and Diversity.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42327314},
issn = {2692-8205},
abstract = {Bi-directional maternal-fetal exchange during pregnancy creates a long-term microchimerism (Mc) legacy in both individuals, but its presence and cellular fate in human brain are largely unknown. We studied surgically resected epilepsy brain specimens with targetable maternal polymorphisms using polymorphism-specific quantitative PCR. Maternal Mc was prevalent, detectable in 70% of patients, and often at striking quantities spanning temporal, frontal, parietal, and hippocampal regions. Next, we employed single nucleus RNA profiling using cellector, a genetic demultiplexing tool designed to detect rare allogeneic cells. We identified Mc across major neural and glial populations. Finally, analysis of publicly available snRNA-seq datasets from neurotypical brains from gestation to late adulthood further revealed widespread Mc, persisting into advanced age, and preferentially adopting L2/3 intratelencephalic neuronal or microglial/macrophage-like fates. These data show that naturally acquired Mc is prevalent, diverse, and persistent in human brain, inviting reconsideration of what constitutes "self," with broad implications for health and disease.},
}

@article {pmid42821238,
year = {2026},
author = {, and Betts, AC and Baker, KS and Blaes, AH and Devine, KA and Hahn, EE and Miller, KA and Parsons, HM and Yi, JC},
title = {Understanding and advancing alignment of the national standards for cancer survivorship care for adolescents and young adults: challenges and opportunities.},
journal = {Journal of cancer survivorship : research and practice},
volume = {},
number = {},
pages = {},
pmid = {42821238},
issn = {1932-2267},
abstract = {PURPOSE: Adolescent and young adult (AYA) cancer survivors experience substantial late and long-term effects and require high-quality survivorship care. This work examines methodological challenges and related opportunities in assessing survivorship care availability, utilization, and key barriers and facilitators for AYAs, using the new National Standards for Cancer Survivorship Care as a guiding framework.

METHODS: Studies were conducted across nine geographically diverse health care systems in seven states (CA, FL, MN, NJ, NY, TX, WA), including seven NCI-designated comprehensive cancer centers, a large integrated health care system, and a county safety-net hospital. Designs included retrospective cohort and mixed methods approaches. Data collection methods comprised EHR abstraction; surveys of AYAs, clinicians, and administrators; and in-depth interviews and/or focus groups with AYAs, clinicians, and administrators. Across studies, AYAs were diagnosed between 2014 and 2024, were 15-44 years old at diagnosis, predominantly female, and racially and ethnically diverse, and had common AYA cancers.

RESULTS: Studies encountered challenges in defining survivorship care, accounting for AYA-specific factors, and addressing the complexity of survivorship care and the NCI Standards. First, we observed difficulties in defining and operationalizing survivorship care components, particularly in EHR data and across audiences who differed in how they understood survivorship care. Second, AYA-related factors such as geographic mobility, insurance changes, and fragmented care during young adulthood complicated assessment, especially for longitudinal analyses. Finally, the complexity of survivorship care and of the standards themselves posed substantial measurement challenges. In this context, collaboration and integration of data within and across AYA survivorship studies represent key research opportunities. Addressing known AYA barriers and priorities will be critical for guiding how the survivorship standards are evaluated and incorporated into clinical practice for AYAs.

Advancing the National Standards for Cancer Survivorship Care for AYAs requires nuanced approaches that integrate multiple perspectives, data sources, and care contexts.},
}

@article {pmid42821692,
year = {2026},
author = {Gan, Q and Li, W and Lex, RK and Ying, Z and Beronja, S},
title = {Loss of the tumor suppressor p53 generates a signaling gradient that drives epithelial clonal expansion.},
journal = {Science (New York, N.Y.)},
volume = {394},
number = {6819},
pages = {eaed3065},
doi = {10.1126/science.aed3065},
pmid = {42821692},
issn = {1095-9203},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; K99 DE029229/DE/NIDCR NIH HHS/United States ; R00 DE029229/DE/NIDCR NIH HHS/United States ; R01 DE034100/DE/NIDCR NIH HHS/United States ; R01 AR070780/AR/NIAMS NIH HHS/United States ; },
mesh = {Animals ; Mice ; Cell Differentiation ; Clone Cells ; *Epidermis/metabolism ; *Keratinocytes/cytology ; *Stem Cells/cytology ; *Tumor Suppressor Protein p53/genetics/metabolism ; Ubiquitin Thiolesterase/metabolism/genetics ; *Wnt Signaling Pathway ; Male ; Female ; Mice, Inbred C57BL ; },
abstract = {Although tumor protein p53 (TP53) mutations are among the most common lesions in epithelial cancers, how p53 loss drives unrestrained clonal expansion remains unclear. Working with mouse epidermis, we found that p53 suppresses clonal expansion by limiting progenitor self-renewal. Integrating chromatin immunoprecipitation sequencing, transcriptional analyses, and genetic screens, we identified a p53-dependent network controlling progenitor renewal and differentiation, in which secreted frizzled-related protein 1 (Sfrp1), low-density lipoprotein receptor-related protein 1 (Lrp1), and ubiquitin-specific peptidase 22 (Usp22) were direct targets of p53 and the most genetically upstream components. Their suppression after p53 loss generated a radial gradient of Wnt activity across mutant clones. Genetic manipulation showed that a Wnt activity gradient, rather than uniform elevation, was associated with sustained clonal expansion. These findings identify spatial organization as a determinant of clonal behavior and a mechanism by which TP53 inactivation drives tissue colonization.},
}

Animals
Mice
Cell Differentiation
Clone Cells
*Epidermis/metabolism
*Keratinocytes/cytology
*Stem Cells/cytology
*Tumor Suppressor Protein p53/genetics/metabolism
Ubiquitin Thiolesterase/metabolism/genetics
*Wnt Signaling Pathway
Male
Female
Mice, Inbred C57BL

@article {pmid42821736,
year = {2026},
author = {Grommes, C and Nayak, L and Kallam, A and Peereboom, D and Ambady, P and Mendez, JS and Aregawi, D and Sumrall, A and Omuro, A and Iwamoto, FM and Dietrich, J and Umemura, Y and Munker, R and Chukwueke, UN and Schaff, LR and Ip, A and Gupta, NK and Drappatz, J and Venur, VA and Peters, KB and Ho, KG and Merrell, R and Prados, S and Takazawa, A and Aoi, A and Batchelor, TT},
title = {Efficacy and safety of tirabrutinib monotherapy for relapsed/refractory primary CNS lymphoma: PROSPECT phase 2 trial.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2026034926},
pmid = {42821736},
issn = {1528-0020},
abstract = {Primary central nervous system lymphoma (PCNSL) is an aggressive subtype of non-Hodgkin lymphoma with a poor prognosis, high rate of refractory or relapsed (R/R) disease, and no established standard of care for R/R PCNSL. This phase 2 study evaluated the efficacy and safety of tirabrutinib, a potent, highly selective, second-generation Bruton tyrosine kinase inhibitor, in patients with R/R PCNSL in the US. In the open-label PROSPECT study, adults with R/R PCNSL whose disease progressed on or after ≥1 high-dose methotrexate-based therapy received once-daily oral tirabrutinib 480 mg. The primary endpoint was overall response rate (ORR), and secondary endpoints included complete response (CR) rate, duration of response (DOR), and time to response (TTR), as assessed by independent review committee. Safety was assessed by frequency and severity of treatment-emergent adverse events (TEAEs). Among 48 enrolled patients, median follow-up was 11.5 months, ORR was 67% (95% confidence interval [CI], 52-80), and CR rate was 44% (95% CI, 29-59). Median DOR was 9.3 months (95% CI, 4.6-14.6), and median TTR was 1.0 month (range, 0.9-3.7). Treatment-related TEAEs occurred in 36 patients (75%), most commonly anemia (19%), maculopapular rash (17%), fatigue (15%), neutropenia (15%), lymphocytopenia (15%), pruritus (15%), and other rash (15%). Grade ≥3 treatment-related TEAEs occurred in 13 patients (27%), most commonly neutropenia (8%) and maculopapular rash (6%). One death (bronchopulmonary aspergillosis) was treatment related. In patients with R/R PCNSL, once-daily oral tirabrutinib monotherapy resulted in rapid and durable responses and demonstrated a favorable safety profile. This trial was registered at www.clinicaltrials.gov as NCT04947319.},
}

@article {pmid42821836,
year = {2026},
author = {Nwogu, IB and Kreif, N and Khan, HM and Etzioni, R and Carlson, JJ},
title = {Real-World Comparative Effectiveness of Abiraterone, Apalutamide, Enzalutamide, and Docetaxel Doublets for Metastatic Hormone-Sensitive Prostate Cancer.},
journal = {JCO oncology practice},
volume = {},
number = {},
pages = {OP2600493},
doi = {10.1200/OP-26-00493},
pmid = {42821836},
issn = {2688-1535},
abstract = {PURPOSE: To evaluate the real-world comparative effectiveness of androgen receptor pathway inhibitors (ARPIs)-abiraterone, apalutamide, enzalutamide-and docetaxel, plus androgen-deprivation therapy (ADT) for metastatic hormone-sensitive prostate cancer (mHSPC).

METHODS: We identified US men with mHSPC who initiated ADT within 4 months of diagnosis and were treated with abiraterone, apalutamide, enzalutamide, or docetaxel within 4 months of ADT initiation between January 2019 and December 2023, with follow-up through June 2025. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Secondary outcomes included time to metastatic castration-resistant prostate cancer (mCRPC) progression (TTP) and time to new treatment initiation (TTNT). Cox proportional hazard and Fine-Gray models with overlapping propensity score weights were used to estimate primary and secondary outcomes, respectively. Subgroup analyses by timing of metastasis and sensitivity analyses using inverse probability of treatment weights were conducted for primary outcomes.

RESULTS: Among 9,141 US men with mHSPC, ARPI doublets demonstrated superior PFS versus docetaxel doublets (abiraterone: adjusted hazard ratio [aHR], 0.60 [95% CI, 0.55 to 0.66]; apalutamide: aHR, 0.64 [95% CI, 0.56 to 0.73]; enzalutamide: aHR, 0.57 [95% CI, 0.51 to 0.64]), with no significant differences among ARPI regimens. OS was comparable among all doublet regimens. Neither PFS nor OS differed by timing of disease. TTP (abiraterone: aHR, 0.52 [95% CI, 0.47 to 0.58]; apalutamide: aHR, 0.59 [95% CI, 0.52 to 0.68]; enzalutamide: aHR, 0.51 [95% CI, 0.45 to 0.57]) and TTNT (abiraterone: aHR, 0.46 [95% CI, 0.42 to 0.51]; apalutamide: aHR, 0.53 [95% CI, 0.46 to 0.61]; enzalutamide: aHR, 0.47 [95% CI, 0.42 to 0.53]) showed similar patterns favoring ARPI doublets. Sensitivity analyses showed consistent findings.

CONCLUSION: ARPI doublets demonstrated superior PFS but similar OS compared with docetaxel doublet, with no differences among individual ARPIs. Patients receiving ARPI doublets were less likely to progress to mCRPC or initiate new treatment.},
}

@article {pmid42690622,
year = {2026},
author = {Braun, KA and Garcia, NM and Ahmed, MA and Tu, DS and Walter, SI and Wrenn, ED and Dean, ME and Katiyar, N and Lawlor, ER},
title = {Menin inhibition impairs metastatic colonization of Ewing sarcoma.},
journal = {JCI insight},
volume = {11},
number = {19},
pages = {},
doi = {10.1172/jci.insight.202419},
pmid = {42690622},
issn = {2379-3708},
mesh = {*Proto-Oncogene Proteins/genetics/antagonists & inhibitors/metabolism ; *Sarcoma, Ewing/genetics/pathology/drug therapy/metabolism ; Animals ; Humans ; Mice ; Cell Line, Tumor ; Proto-Oncogene Proteins c-myc/metabolism/genetics ; Gene Expression Regulation, Neoplastic/drug effects ; Cell Proliferation/drug effects ; *Bone Neoplasms/genetics/pathology/drug therapy ; Female ; Neoplasm Metastasis ; },
abstract = {Menin is a scaffolding protein that interacts with context-specific partners to regulate gene expression. In rearranged mixed-lineage leukemia, Menin-MLL interactions drive leukemogenesis and Menin inhibitors have been FDA approved for these cancers. We previously reported that Menin promotes oncogenic phenotypes in Ewing sarcoma (EwS). Here, we sought to define EwS-specific functions of Menin and determine if Menin inhibitors could be therapeutically leveraged for these tumors. Genetic KO of Menin had no effect on EwS cell proliferation in vitro, but metastatic potential of Menin-depleted cells in vivo was impaired. Transcriptional profiling of Menin-KO cells in vitro showed reproducible downregulation of MYC signature genes and upregulation of developmental programs. Conversely, transcriptional rewiring of developmental genes and restoration of MYC target gene expression were evident in tumors that arose from Menin-KO cells. Exposing EwS cells to the Menin inhibitor VTP50469 (revumenib) inhibited expression of MYC targets, and coimmunoprecipitation studies detected Menin-MYC interactions that were partially disrupted by the drug. Metastatic colonization of disseminated EwS cells in vivo was significantly inhibited in mice fed VTP50469 chow. Together these findings implicate Menin as a mediator of EwS metastasis and suggest that Menin inhibitors warrant investigation as novel therapeutics for patients with high-risk disease.},
}

*Proto-Oncogene Proteins/genetics/antagonists & inhibitors/metabolism
*Sarcoma, Ewing/genetics/pathology/drug therapy/metabolism
Animals
Humans
Mice
Cell Line, Tumor
Proto-Oncogene Proteins c-myc/metabolism/genetics
Gene Expression Regulation, Neoplastic/drug effects
Cell Proliferation/drug effects
*Bone Neoplasms/genetics/pathology/drug therapy
Female
Neoplasm Metastasis

@article {pmid42816122,
year = {2026},
author = {Bry, V and Tran, A and Egan, T and Ford, E and Meyer, J},
title = {A technology-specific risk analysis of surface guided radiation therapy.},
journal = {Journal of applied clinical medical physics},
volume = {27},
number = {10},
pages = {e70837},
pmid = {42816122},
issn = {1526-9914},
mesh = {Humans ; *Radiotherapy Planning, Computer-Assisted/methods ; *Radiotherapy, Image-Guided/methods ; Radiotherapy Dosage ; Risk Assessment ; Workflow ; Patient Positioning ; Radiotherapy, Intensity-Modulated/methods ; *Radiosurgery/methods ; *Healthcare Failure Mode and Effect Analysis ; Patient Safety ; *Breast Neoplasms/radiotherapy ; },
abstract = {BACKGROUND: Surface Guided Radiation Therapy (SGRT) has become an increasingly important tool that complements x-ray imaging to improve patient safety for setup, respiratory tracking, and motion monitoring. As SGRT is integrated into clinical workflows, its complexity can introduce potential risk of process-related errors. These risks may depend on workflow design, system integration, equipment configuration, and technology specific features. As SGRT continues to expand across a wider range of treatment sites and clinical applications, comprehensive evaluation of institutional workflows is recommended to support safe and effective implementation.

PURPOSE: This study aimed to identify and evaluate safety risks associated with the clinical use of SGRT using Failure Mode and Effects Analysis (FMEA). Emphasis was placed on workflow processes, system integration, and equipment-specific characteristics within a clinical environment to inform risk mitigation strategies and support safe implementation.

METHODS: A multidisciplinary team performed an FMEA of SGRT related procedures and workflows. A process map was developed to define the scope of clinical applications, including tattoo free setup, free-breathing and deep-inspiration breath-hold (DIBH) breast treatments, prone patient positioning and real-time motion monitoring for stereotactic body radiation therapy (SBRT) patients across body sites. For each process step, team members identified potential failure modes associated with the clinical workflow and environment, including the integration of a C-RAD SGRT system with Elekta linear accelerators. Scoring was performed according to AAPM TG-100 guidelines, using severity (S), occurrence (O), and detectability (D) to calculate the Risk Priority Number (RPN). Failure modes were then ranked by RPN, and those with scores greater than or equal to 100 were selected for further analysis and development of mitigation strategies.

RESULTS: Thirty-eight failure modes were identified, with nine having RPN scores greater than or equal to 100 (S = 5-8, O = 2-5, and D = 5-9). High risk failure modes were most associated with the DIBH workflow, particularly respiratory trace acquisition, respiratory trace configuration, and x-ray image verification. Additional high risk failure modes were identified in treatment preparation and system quality assurance processes, including manual data import, template selection, calibration, and daily QA procedures. These risks were primarily associated with workflow-dependent processes involving user interaction and coordination between integrated clinical systems.

CONCLUSIONS: This FMEA identified workflow, system integration and equipment related vulnerabilities associated with SGRT implementation. The findings emphasize the importance of risk assessments tailored to specific clinical workflows and treatment environments and support the development of targeted mitigation strategies for safe clinical use.},
}

Humans
*Radiotherapy Planning, Computer-Assisted/methods
*Radiotherapy, Image-Guided/methods
Radiotherapy Dosage
Risk Assessment
Workflow
Patient Positioning
Radiotherapy, Intensity-Modulated/methods
*Radiosurgery/methods
*Healthcare Failure Mode and Effect Analysis
Patient Safety
*Breast Neoplasms/radiotherapy

@article {pmid42816564,
year = {2026},
author = {Lakkaraja, M and Mauguen, A and Hosszu, K and McAvoy, D and Stewart, V and Schmidt, G and Levine, JE and Perales, MA and Giralt, SA and Baker, KS and Boelens, JJ},
title = {ATG exposure in T replete transplant for hematological malignancies: Real world analysis from BMT CTN 1202.},
journal = {Bone marrow transplantation},
volume = {},
number = {},
pages = {},
pmid = {42816564},
issn = {1476-5365},
support = {NIH/NCI Cancer Center Support Grant P30 CA015704//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; NIH/NCI Cancer Center Support Grant P30 CA008748//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; NIH/NCI Cancer Center Support Grant P30 CA008748//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; NIH/NCI Cancer Center Support Grant P30 CA008748//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; NIH/NCI Cancer Center Support Grant P30 CA015704//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; NIH/NCI Cancer Center Support Grant P30 CA008748//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; ASH Scholar//American Society of Hematology (ASH)/ ; },
abstract = {Traditional weight-based dosing results in variable rabbit anti-thymocyte globulin (rATG) clearance, delaying CD4+Tcell-immune-reconstitution (CD4 + IR) and impacting outcomes. In a retrospective pharmacokinetic/pharmacodynamic analysis of patients undergoing first T-replete hematopoietic cell transplantation (HCT), enrolled on BMT CTN 1202, we estimated post-HCT rATG-exposures as area under the curve (arbitrary unit per day/milliliter [AUxd/mL]) using a validated pharmacokinetic-model. Results were compared to patients who did not receive rATG. Previously defined post-HCT rATG-exposure groups: A: < 30, B:30-55 and C: ≥ 55 AUxd/mL were correlated with outcomes of interest using cox-proportional-hazard and cause-specific-hazards models. 325 patients (median age 51 years) were included: 228 received rATG. Median post-HCT rATG-exposure was 44.1 (Range 6.2-125.0). Among patients who received rATG, higher exposure correlated with worse five-year overall survival (OS) (no-ATG:51%; group A:67%; B:49%; C:34%, p = 0.01), higher five-year relapse incidence (no-ATG:31%; A:27%; B: 42%; C: 58%, p < 0.001) and lower CD4 + IR (no-ATG:64%; A:73%; B:51%; C:19%, p = 0.001). Grade 2-4 acute graft versus host disease (GVHD) rates were: no-ATG:40% ; A:26%, B:39%, C:35%, (p = 0.44). Any rATG-exposure was associated with lower moderate/severe chronic GVHD (HR:0.63, p = 0.025). Low post-HCT rATG-exposure (< 30AUxd/mL) but not absent correlated with higher OS, lower relapse, and lower GVHD related deaths. Model-based-dosing could be used to target optimal post-HCT rATG-exposure and improve HCT outcomes.},
}

@article {pmid42816625,
year = {2026},
author = {Dai, A and Ballweg, A and Jogia, W and Rangesa, M and Adintori, PA and Baichoo, M and Funnell, T and Fei, T and Waters, NR and Swartz, A and Sahu, S and Gipson, B and Raj, SS and Hayase, E and Pierce, Z and Wu, K and Smith, N and Neuberger, J and Warren, A and da Silva, MB and Miltiadous, O and Zuanelli Brambilla, C and Buchan, ML and Peets, TK and Gradissimo, A and Amoretti, LA and Duan, C and Zhang, C and Matheis, F and Sullivan, AP and Slingerland, JB and Clurman, AG and Brereton, DG and Giardina, PA and Gomes, ALC and Johnson, AJ and Knights, D and Jenq, RR and Markey, KA and Perales, MA and Giralt, SA and van den Brink, MRM and Schluter, J and Peled, JU},
title = {Sugar-rich foods exacerbate antibiotic-induced microbiome disruption.},
journal = {Nature},
volume = {},
number = {},
pages = {},
pmid = {42816625},
issn = {1476-4687},
abstract = {Diet shapes the composition of the gut microbiota[1]; however, the specific effects of distinct food groups on microbiome dynamics are unclear, particularly in circumstances of extreme perturbation. Here we evaluated the relationship between diet and intestinal microbiome dynamics by precisely tracking 9,419 meals consumed by 173 patients who were hospitalized for haematopoietic cell transplantation and analysing subsequent microbiome changes. Bayesian inference applied to data from 158 patients with paired longitudinal microbiome samples revealed that the intake of sweets and sugars during antibiotic exposure predicted exacerbated microbial dysbiosis, manifesting as lowered α-diversity and greater expansion of the pathobiont Enterococcus. Experiments in mice also showed that sucrose supplementation increased and prolonged antibiotic-induced Enterococcus expansion. These data suggest that avoiding a diet rich in simple sugars during antibiotic treatment may mitigate microbiota disruption. Further studies in independent cohorts will offer opportunities to generalize these findings and evaluate microbiota-sparing interventions.},
}

@article {pmid42817751,
year = {2026},
author = {Mizuno, S and Gras, L and Baaij, LG and Koster, L and D'Souza, A and Hari, PN and Estrada-Merly, N and Saber, W and Cowan, AJ and Iida, M and Okamoto, S and Takamatsu, H and Kawamura, K and Kodera, Y and Hamad, N and Ko, BS and Liam, C and Ho, KW and Goh, AS and Keat, TS and Elhaddad, AM and Bazarbachi, A and Chaudhry, BQUN and Alfar, R and Bekadja, MA and Benakli, M and Ortiz, CAF and Riva, E and Verburgh, E and Galeano, S and Bass, F and Mian, H and McCurdy, A and Wang, FR and Neumann, D and Koh, MBC and Snowden, JA and Schönland, S and McLornan, DP and Hayden, PJ and Balari, AMS and Greinix, HT and Aljurf, M and Atsuta, Y and De Wreede, LC and Rondelli, D and Niederwieser, DW and Garderet, L},
title = {Erratum to: "The impact of age on survival and excess mortality after autologous hematopoietic cell transplantation in newly diagnosed multiple myeloma patients".},
journal = {Haematologica},
volume = {111},
number = {10},
pages = {3544-3545},
pmid = {42817751},
issn = {1592-8721},
}

@article {pmid42817823,
year = {2026},
author = {Yanagi, KS and Lin-Moore, AT and Gordon, NC and Lins, JJ and Coyne, EM and Meininger, KL and Moy, SL and Stinson, LA and Walsh, MB and Gallati, M and Mahapatra, A and Aderogba, R and Jaworski, A and Hart, AC},
title = {A genetic screen for suppressors of neuron degeneration in a C. elegans sod-1G85R model of Amyotrophic Lateral Sclerosis.},
journal = {G3 (Bethesda, Md.)},
volume = {},
number = {},
pages = {},
doi = {10.1093/g3journal/jkag281},
pmid = {42817823},
issn = {2160-1836},
abstract = {Genetic variants in superoxide dismutase 1 (SOD1) cause the progressive neurodegenerative disease Amyotrophic Lateral Sclerosis (ALS). Treatments for this disease are limited, and the unique vulnerability of cholinergic and glutamatergic motor neurons to degeneration seen in ALS patients is not clearly understood. Identifying genetic modifiers of neurodegeneration can provide insight into the selective vulnerability of motor neurons in ALS and may accelerate identification of novel therapeutic targets. Here, we describe a forward genetic screen for suppressors of the stress-induced glutamatergic neuron degeneration in a single-copy C. elegans model of sod-1G85R. Used two different screening strategies, we identified 53 suppressor lines that decreased glutamatergic neuron degeneration to varying degrees. To rapidly identify suppressor genes, we sequenced suppressor lines and identified candidate suppressor genes based on frequency of de novo exonic mutations and previously published work. Two candidates were tested and excluded as suppressor genes: erh-1 and imph-1. For a subset of unidentified suppressor lines, we determined if cholinergic neurodegeneration was also suppressed; roughly one-third of suppressor lines showed no corresponding cholinergic neuron rescue, suggesting that mechanisms involved in cholinergic and glutamatergic degeneration are at least partially divergent. This study outlines the first unbiased genetic screen in a knock-in model of SOD1 neurodegeneration, describes a cohort of candidate suppressor lines with decreased SOD1-dependent neurodegeneration, excludes two candidates and discusses approaches for suppressor mutation isolation and gene identification.},
}

@article {pmid42820607,
year = {2026},
author = {Wei, W and Basu, E and Kushner, BH and Lakkaraja, M and Kramer, K and Iglesias Cardenas, F and Cheung, NV and Pandit-Taskar, N and Modak, S},
title = {Single Autologous Stem Cell Rescue After Single or Tandem [131]I-Metaiodobenzylguanidine Therapy, With or Without Subsequent Chemotherapy, for Resistant Neuroblastoma: Feasibility, Toxicity, and Response.},
journal = {Pediatric blood & cancer},
volume = {},
number = {},
pages = {e70725},
doi = {10.1002/1545-5017.70725},
pmid = {42820607},
issn = {1545-5017},
abstract = {BACKGROUND: Myelosuppression is the principal toxicity of [131]I-metaiodobenzylguanidine (MIBG) therapy for neuroblastoma and can be mitigated with autologous stem cell rescue (ASCR). We evaluated whether sequential [131]I-MIBG therapy with chemotherapy could be supported by a single ASCR.

METHODS: This is a retrospective analysis of patients who completed a single-arm expanded access study (NCT00107289) in which 96 patients were treated with [131]I-MIBG therapy between 2008 and 2020 at Memorial Sloan Kettering Cancer Center. Patients could receive one or two [131]I-MIBG treatments, with or without chemotherapy. Myelosuppression was rescued with a single ASCR.

RESULTS: Fifty-three patients received single-MIBG therapy, 43 received tandem MIBG therapy, and 61 received chemotherapy following single (n = 33) or tandem (n = 28) MIBG. ASCR was required in 11, 8, and 58 patients after single MIBG therapy, tandem MIBG therapy, and chemotherapy, respectively. Hematologic recovery with a single ASCR was adequate, with neutrophil and platelet engraftment in 100% and 90% of patients. Anti-neuroblastoma activity was modest, with an overall objective response rate (complete/partial/minor response; ORR) of 15% after the first MIBG treatment. Tandem MIBG therapy did not meaningfully improve response (ORR; 21%), whereas chemotherapy after single MIBG therapy produced modest response improvement (ORR; 35%).

CONCLUSION: In selected patients with resistant neuroblastoma, sequential MIBG therapy with chemotherapy can be delivered with a single ASCR, potentially conserving stem cell aliquots. Given the modest responses and the toxicities encountered, novel agents rather than tandem MIBG therapy or chemotherapy should be considered to optimize the role of MIBG therapy.},
}

@article {pmid42820770,
year = {2026},
author = {Rogers, JR and Ward, ZJ and Feraco, AM and Castellino, SM and Stratton, KL and Leisenring, WM and Armstrong, GT and Chow, EJ and Howell, RM and Hudson, MM and Kelly, KM and Morton, LM and Oeffinger, KC and Smith, SA and Diller, L and Yeh, JM},
title = {Immunotherapy-Based Therapies in Pediatric Hodgkin Lymphoma: Potential to Narrow the Gap in Long-Term Survival.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djag353},
pmid = {42820770},
issn = {1460-2105},
support = {P30 CA021765/CA/NCI NIH HHS/United States ; R01 CA227576/CA/NCI NIH HHS/United States ; U24 CA055727/CA/NCI NIH HHS/United States ; },
abstract = {Pediatric advanced-stage Hodgkin lymphoma (HL) is highly curable, yet survivors treated with historical regimens face substantial late morbidity and excess mortality. Immunotherapy-based frontline therapies improve disease control, but late toxicities remain unknown. We developed a simulation model to project lifetime outcomes after contemporary brentuximab vedotin- or nivolumab-containing regimens using trial data (COG AHOD1331 and SWOG S1826), Childhood Cancer Survivor Study data, and national databases. We assessed how frontline and relapse therapy changes could influence long-term survival and late-effect outcomes, with sensitivity analyses to evaluate potential immunotherapy-related late mortality. Compared with expected survival at age 50 in the general population, HL survival was 86% at age 50 after historical regimens and 92-93% after contemporary immunotherapy-based therapies. Survival gains persisted unless immunotherapy-related late mortality exceeded approximately 8%. These projections suggest contemporary regimens may narrow the long-term survival gap while reducing late-effect burden.},
}

@article {pmid42821092,
year = {2026},
author = {Adamson, B and Gelderblom, HC and Miner, MD and Corey, L},
title = {On the economics of broadly neutralizing monoclonal antibodies for HIV prevention in high-income countries.},
journal = {Journal of comparative effectiveness research},
volume = {},
number = {},
pages = {e260120},
doi = {10.57264/cer-2026-0120},
pmid = {42821092},
issn = {2042-6313},
abstract = {Aim: To quantify the market opportunity and economic impact of broadly neutralizing monoclonal antibodies (bnAbs) as a novel HIV prevention modality in high-income countries. Materials & methods: Using a decision-tree and revenue model applied to an eligible US population of 1299,708 individuals and projecting to 2040, bnAbs are estimated to capture 1 in 8 PrEP users (12.5% of PrEP users, 95% credible interval 7.3% to 21.1%, equivalent to 8.0% of the prevention-eligible population) following assumed US FDA approval in 2030. All estimates are scenario based and conditional on assumed pricing, uptake and behavior; none are observed outcomes. Critically, roughly half of projected bnAb users, nearly 52,000 individuals, would not otherwise use any biomedical HIV prevention, representing a net expansion of PrEP users (95% credible interval: 21,859-95,581). US manufacturer revenue totaled $12.0 billion discounted at 3% per year to 2030 (95% credible interval $6.2 billion to $21.9 billion), equivalent to $14.5 billion undiscounted, over the 11 years from approval to 2040. Total US payer spending rose 3.6% ($463.6 million annually), though the credible interval crosses zero, and the mean cost per prevention user decreased provided bnAbs are priced at the modeled list price of $14,000 per year, below existing injectable PrEP options. Conclusion: Under the assumptions modeled here, bnAbs could reach roughly one in eight PrEP users in high-income countries, about half of them people not otherwise using biomedical prevention. Whether this translates into an attractive commercial opportunity, and whether per-user prevention costs fall or rise, depends principally on how bnAbs are priced relative to long-acting injectable PrEP. These are projections conditional on assumed efficacy, pricing and adoption behavior, not observed outcomes.},
}

@article {pmid42809774,
year = {2026},
author = {Laing, SS and Gallegos, D and Amberson, T and Sheffield, P and Shannon Dorcy, K},
title = {Community Health Center Staff Evaluation of the Acceptability, Usefulness and Ease of Implementation of Evidence-Based Organizational-Level Interventions to Promote Healthcare Workforce Well-Being.},
journal = {Journal of occupational and environmental medicine},
volume = {},
number = {},
pages = {},
doi = {10.1097/JOM.0000000000003896},
pmid = {42809774},
issn = {1536-5948},
abstract = {OBJECTIVE: Study examined community health center healthcare staff's assessment of the acceptability, usefulness and ease of implementation of evidence-based organizational-level strategies to reduce burnout and improve well-being.

METHODS: Four focus groups with a total of 22 healthcare professionals from four occupational domains: medical providers, medical support staff, dental staff and nursing staff. We analyzed the data using Rapid Qualitative Analysis enabling timely results to leaders.

RESULTS: Participants highlighted organizational strengths (culture of teamwork and collaboration), and challenges (increased workload and inconsistent workflow). Respondents identified (1) workflow redesign; (2) advanced team-based care; (3) person-centered leadership training; and (4) flexible work schedules as organizational-level interventions that are acceptable, useful, easy to implement and therefore feasible to support workforce wellness.

CONCLUSIONS: Staff engagement in identification and implementation of health promotive strategies is key to long-term burnout reduction and workplace health promotion.},
}

@article {pmid42809793,
year = {2026},
author = {Zeng, S and Owens, L and Liu, LJ and Carlsson, S and Fainberg, JS and Laudone, VP and Schoen, MW and Garraway, IP and Etzioni, R},
title = {TrajSurv-mPC: Learning From Prostate-Specific Antigen Trajectories for Interpretable and Generalizable Survival Prediction in Metastatic Prostate Cancer.},
journal = {JCO clinical cancer informatics},
volume = {10},
number = {3},
pages = {e2500328},
doi = {10.1200/CCI-25-00328},
pmid = {42809793},
issn = {2473-4276},
support = {I01 CX002946/CX/CSRD VA/United States ; },
mesh = {Humans ; Male ; *Prostatic Neoplasms/mortality/blood/pathology/therapy ; *Prostate-Specific Antigen/blood ; Prognosis ; Neoplasm Metastasis ; *Deep Learning ; Predictive Learning Models ; Biomarkers, Tumor ; Aged ; },
abstract = {PURPOSE: Conventional prognostic models for metastatic prostate cancer (mPC) typically rely on summary features like prostate-specific antigen (PSA) doubling time, often obscuring informative longitudinal dynamics. We developed TrajSurv-mPC, a flexible deep learning framework that analyzes full premetastasis patient trajectories-including serial PSA and treatments-to improve postmetastasis overall survival (OS) prediction.

METHODS: The TrajSurv-mPC framework was developed and evaluated using two independent cohorts: Memorial Sloan Kettering (MSK; n = 403) and Veterans Affairs (VA; n = 9,984). To demonstrate its architectural robustness, the framework's sequential modeling was implemented with both Long Short-Term Memory (LSTM) and Transformer backbones. The models used baseline characteristics alongside longitudinal PSA and treatment data to predict OS from the time of metastasis detection. Performance was compared against models using summary features. Generalizability was assessed via external validation (training on a harmonized VA subcohort; testing on MSK). Interpretability was explored through post hoc hidden state clustering, a simulation study, and a case study.

RESULTS: Compared with summary-feature models (C-indices: 0.650-0.677 internally; 0.635-0.651 externally), the TrajSurv-mPC framework achieved C-indices of 0.723-0.747 (MSK) and 0.711-0.754 (VA) in internal validations, and 0.693 (LSTM, P = .02) and 0.708 (Transformer, P = .008) in cross-cohort external validations across both architectures. Clustering stratified distinct prognostic groups (P < .001). Furthermore, simulation and case studies showed that predicted risk varied in clinically plausible directions across different treatment response trajectories.

CONCLUSION: By modeling the complete premetastasis PSA trajectory, the TrajSurv-mPC framework improves prognostic risk prediction in mPC. Its robust performance across different sequential backbones demonstrates the generalizable added value of dynamic patterns in distinct populations. Combining this framework with complementary measures based on imaging or genomics may enhance personalization of mPC management.},
}

Humans
Male
*Prostatic Neoplasms/mortality/blood/pathology/therapy
*Prostate-Specific Antigen/blood
Prognosis
Neoplasm Metastasis
*Deep Learning
Predictive Learning Models
Biomarkers, Tumor
Aged

@article {pmid42810513,
year = {2026},
author = {Shah, PD and Schwartz, J and Bacci, JL and Calo, WA and Li, L and Glascock, M and Ndugulile, M and Watabayashi, K},
title = {Pilot evaluation of a clinical decision support system package to facilitate proactive HPV vaccination in community pharmacies.},
journal = {Journal of the American Pharmacists Association : JAPhA},
volume = {},
number = {},
pages = {103533},
doi = {10.1016/j.japh.2026.103533},
pmid = {42810513},
issn = {1544-3450},
abstract = {BACKGROUND: Human papillomavirus (HPV) vaccine coverage among US adolescents remains below national targets. Community pharmacies are accessible vaccination sites, but proactive HPV vaccination is hindered by fragmented pharmacy management and immunization information system (IIS) workflows. Clinical decision support systems (CDSS) may reduce these workflow barriers, yet evidence for their utility in pharmacy-based HPV vaccination is limited.

OBJECTIVE: To pilot-test a CDSS package designed to support proactive adolescent HPV vaccination in community pharmacies and to assess early-phase implementation and behavioral outcomes.

METHODS: CDSS were co-designed with independent pharmacies and technology partners and implemented in a single arm pre/post pilot conducted between April-August 2024. Six pharmacies in Washington State deployed a CDSS package, integrating seven linked components spanning pharmacy-level planning, staff-level point-of-care supports, and parent/patient-level interactions. Pharmacy staff completed baseline and follow-up surveys assessing implementation outcomes (acceptability, appropriateness, feasibility) and targeted vaccination behaviors (recommendation practices, self-efficacy). Pre/post changes were evaluated using descriptive statistics and Wilcoxon signed-rank tests.

RESULTS: Eighteen staff completed surveys; 13 completed pre/post surveys. HPV vaccine recommendations increased from 77% to 100%. Routine recommendation at ages 9-10 increased from 15% to 46%, with fewer staff recommending vaccine at older ages. Self-efficacy for setting vaccination goals improved significantly (mean 3.4 to 4.2/5.0; p=0.012). Implementation outcomes met the threshold for high positive appraisals (mean ≥3.5/5.0) for acceptability (4.0), appropriateness (3.7), and feasibility (3.6). The most adopted CDSS components were the IIS-to-dispensing system data pull (78%), coverage/goal-setting report (72%), and eligibility screening template (72%). Vaccination audit data showed heterogeneous changes across sites.

CONCLUSIONS: A co-designed CDSS package was feasible to deploy in pharmacies and improved proactive HPV recommendation behaviors and goal-setting confidence. However, CDSS alone may be insufficient to drive meaningful increases in HPV vaccination rates, as workflow supports cannot substitute for strategies that actively bring adolescents to the pharmacy.},
}

@article {pmid42810586,
year = {2026},
author = {McDermott, DF and Signoretti, S and Lee, JL and Donskov, F and Tykodi, SS and Tomczak, P and Bjarnason, GA and Larkin, JMG and Kochenderfer, MD and Gafanov, RA and Cristescu, R and Markensohn, J and Nebozhyn, M and Zhang, Y and Peng, X and Rodriguez-Lopez, K and Burgents, J and Perini, RF and Atkins, MB},
title = {Final results and predictive biomarkers of response and long-term outcomes with first-line pembrolizumab monotherapy in advanced renal cell carcinoma in the phase II KEYNOTE-427 study.},
journal = {Annals of oncology : official journal of the European Society for Medical Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.annonc.2026.09.011},
pmid = {42810586},
issn = {1569-8041},
abstract = {BACKGROUND: Previous results from the single-arm, phase II KEYNOTE-427 study showed antitumor activity with first-line pembrolizumab monotherapy in advanced clear cell renal cell carcinoma (ccRCC) and non-clear cell RCC (nccRCC). We report results of the final efficacy and safety analyses and exploratory, predictive biomarker analysis of KEYNOTE-427.

PATIENTS AND METHODS: Eligible participants had histologically confirmed locally advanced, recurrent, or metastatic ccRCC (cohort A) or nccRCC (cohort B) with or without sarcomatoid features, measurable disease per RECIST v1.1, and no prior systemic therapy for advanced RCC. The primary end point was objective response rate (ORR) per RECIST v1.1 by blinded independent central review. Prespecified biomarker objectives were to evaluate the association of clinical outcomes with a T-cell-inflamed gene expression profile (TcellinfGEP), programmed cell death ligand 1 combined positive score (PD-L1 CPS), RCC driver gene mutations, and circulating tumor DNA (ctDNA; cohort A).

RESULTS: After a median (range) follow-up of 61.1 months (54.7-65.5) in cohort A and 56.7 months (47.9-64.0) in cohort B, ORRs were 36.4% and 26.7%, respectively. Continuous TcellinfGEP was positively associated with ORR in cohort A (P=0.0208) and cohort B (P=0.0021). Continuous PD-L1 CPS was positively associated with ORR (P=0.0195) and progression-free survival (PFS; P=0.0307) in cohort A and ORR (P <0.0001), PFS (P=0.0002), and overall survival (OS; P=0.0014) in cohort B. RCC driver gene mutations showed no consistent patterns with ORR in either cohort. In cohort A, participants with detectable ctDNA at baseline had a shorter OS than participants with a ctDNA-negative status (median: 30.5 months [95% CI 18.1-56.4] vs 53.7 months [28.7-not reached]).

CONCLUSIONS: These results show that pembrolizumab is a highly active agent in ccRCC and nccRCC. Insights from the comprehensive analysis of RCC tumor molecular components and ctDNA may facilitate progress toward effective, biomarker-driven precision treatment in advanced RCC.},
}