tbuckley/cabot-search huggingface dataset:
External Validation of a 5-Factor Risk Model for Breast Cancer–Related Lymphedema
Authors: Cherie Lin, Jie Su, Alison J. Wu, Neil Lin, Madison-Shira Hossack, Wei Shi, Wei Xu, Fei-Fei Liu, Jennifer Y. Y. Kwan
Journal: JAMA Network Open (2025)

Importance Secondary lymphedema is a common, harmful side effect of breast cancer treatment. Robust risk models that are externally validated are needed to facilitate clinical translation. A published risk model used 5 accessible clinical factors to predict the development of breast cancer–related lymphedema; this model included a patient’s mammographic breast density as a novel predictive factor. Objective To investigate the external validity of a previously reported 5-factor model by applying it to an independent cohort of patients with breast cancer. Design, Setting, and Participants This prognostic study collected data on a longitudinal cohort of patients with predominantly early-stage breast cancer treated with curative intent at the Princess Margaret Cancer Centre in Toronto, Canada between February 1, 2010, and July 31, 2014, with a median (IQR) follow-up of 4.3 (2.4-7.6) years. The 5 factors (age, body mass index, breast density, nodal burden, and use of axillary lymph node dissection [ALND]) were used as input into the established regression-based model. The analysis was performed from July 2 through August 29, 2024. Exposure Lymphedema after breast cancer treatment. Main Outcomes and Measures Lymphedema-free survival (LFS) was analyzed using Kaplan-Meier analysis, and sensitivity, specificity, and accuracy performance metrics of predicting breast cancer–related lymphedema were calculated. Results A total of 101 female patients (median [IQR] age, 54.8 [48.8-62.3] years) were included in the analysis. These patients had localized or locoregional breast cancer treated with primary lumpectomy (90 [89%]) or mastectomy (11 [11%]); 75 (74%) had no axillary biopsy or sentinel lymph node biopsy; 26 (26%) had undergone ALND; and 38 (38%) had received chemotherapy, 101 (100%) received radiotherapy, and 64 (63%) received hormone therapy. Kaplan-Meier analysis showed a 2-year LFS of 97.5% (95% CI, 94.0%-100.0%) vs 65.0% (95% CI, 47.1%-89.7%) for the low- vs high-risk groups as defined by the 5-factor model ( P &amp;amp;lt; .001). The model sensitivity was 0.83 (95% CI, 0.52-0.98), specificity was 0.89 (95% CI, 0.80-0.94), and accuracy was 0.88 (95% CI, 0.80-0.94) for predicting breast cancer–related lymphedema. Conclusions and Relevance These findings validate the performance of a 5-factor risk model for its prediction of 2-year LFS. Future clinical translation of this model can help with identifying patients at the highest risk of breast cancer–related lymphedema to facilitate closer surveillance and/or preventive management to improve health outcomes and quality of life.
Effect of Pediatric Obesity Treatment on Long-Term Health
Authors: Resthie R. Putri, Pernilla Danielsson, Nils Ekström, Åsa Ericsson, Louise Lindberg, Claude Marcus, Emilia Hagman
Journal: JAMA Pediatrics (2025)

IMPORTANCE Data regarding the long-term impact of treating childhood obesity on the risk of obesity-related events, including premature mortality, are limited. OBJECTIVE To evaluate the long-term effect of different responses to pediatric obesity treatment on critical health outcomes in young adulthood. Design, Setting, and Participants The study included a dynamic prospective cohort of children and adolescents with obesity within The Swedish Childhood Obesity Treatment Register (BORIS) and general population comparators, linked with national registers. Baseline data were collected between 1996 and 2019. Formal analyses for this study was conducted in 2023. Outcomes were assessed from individuals aged 18 to 30 years (2005 to 2020). Participants included children and adolescents aged 6 to 17 years receiving at least 1 year of obesity treatment. General population comparators were matched on a ratio of 1:5 on sex, year of birth, and geographical area. EXPOSURE Pediatric obesity treatment response was based on changes in body mass index standard deviation score and categorized as poor, intermediate, and good response and obesity remission. MAIN OUTCOMES Obesity-related events included type 2 diabetes (T2D), dyslipidemia, hypertension, depression or anxiety, and weight-loss bariatric surgery. Additionally, mortality was assessed. RESULTS Of 6713 individuals (3777 male [56%] and 2936 female [44%]), the median age at obesity treatment initiation was 12.1 (quartile 1; quartile 3: 10.1; 14.3) years and treatment duration was 3.0 (1.8; 4.9) years. For T2D, hypertension, dyslipidemia, weight-loss bariatric surgery, and depression or anxiety outcomes, unadjusted incidence rates tended to decrease with better treatment response and the lowest estimate was observed among general population comparators. Compared with poor response, obesity remission or a good response in obesity treatment was associated with reduced risk of mortality (adjusted hazard ratio [HR], 0.12; 95% CI, 0.03-0.46). Good response was also associated with lower risk of TD2 (HR, 0.42; 95% CI, 0.23-0.77), dyslipidemia (HR, 0.31; 95% CI, 0.13-0.75), and bariatric surgery (HR, 0.42; 95% CI, 0.30-0.58). Obesity remission showed similar reduced risk, but also a reduced risk of hypertension (HR, 0.40; 95% CI, 0.24-0.65). Treatment response was not associated with depression or anxiety. CONCLUSIONS AND RELEVANCE In this study, beneficial pediatric obesity treatment response yielded enduring health benefits, markedly lowering future morbidity and mortality risks in young adulthood.
A change in voice
Authors: Chris Hogan, Marion Alston, Andrew Costerton, Bengi Beyzade, Nick J I Hamilton
Journal: BMJ (2025)

### What you need to know A 45 year old man presents to his general practitioner with a three month history of hoarse voice. The onset was over a short time and was predated by five days of coryzal symptoms. He has no past medical history, takes no regular medications, and smokes 10 cigarettes a day. A change in voice, or dysphonia, describes a perceived alteration in vocal function and can include changes in voice clarity, pitch, loudness, and fatigueability. This term is preferred to vocal hoarseness, which refers to a change in the clarity of the voice only. Dysphonia can have a substantial impact on social and professional quality of life leading to anxiety, depression, social isolation, and inability to work or attend education.1 Dysphonia is common, and in one large retrospective analysis of US insurance claims data, prevalence was 1% of people aged up to 65 years old, with a lifetime incidence of about 30%.2 Clinical assessment of the dysphonic patient can be challenging for a clinician who is unable to visualise the larynx. Here, we aim to help healthcare practitioners working in primary care and the non-specialist setting to understand the clinical features of benign (non-malignant) disease and features that warrant onward referral to ear, nose, throat specialists. ### History
Author Correction: The ZmCPK39–ZmDi19–ZmPR10 immune module regulates quantitative resistance to multiple foliar diseases in maize
Authors: Mang Zhu, Tao Zhong, Ling Xu, Chenyu Guo, Xiaohui Zhang, Yulin Liu, Yan Zhang, Yancong Li, Zhijian Xie, Tingting Liu, Fuyan Jiang, Xingming Fan, Peter Balint-Kurti, Mingliang Xu
Journal: Nature Genetics (2025)
Travel Time as an Indicator of Poor Access to Care in Surgical Emergencies
Authors: Nina M. Clark, Alexandra H. Hernandez, Mia S. Bertalan, Virginia Wang, Sarah L. M. Greenberg, Andrew M. Ibrahim, Barclay T. Stewart, John W. Scott
Journal: JAMA Network Open (2025)

Importance Timely access to care is a key metric for health care systems and is particularly important in conditions that acutely worsen with delays in care, including surgical emergencies. However, the association between travel time to emergency care and risk for complex presentation is poorly understood. Objective To evaluate the impact of travel time on disease complexity at presentation among people with emergency general surgery conditions and to evaluate whether travel time was associated with clinical outcomes and measures of increased health resource utilization. Design, Setting, and Participants This retrospective cohort study used administrative statewide inpatient and emergency department databases with linkage across encounters, including nearly every inpatient or emergency department encounter in the states of Florida and California in 2021. Participants included adult patients who presented to an emergency department with 1 of 5 common emergency surgical conditions. Data were collected from January to December 2021 and analyzed from June to December 2023. Exposure The primary exposure was travel time from the patient’s home to the facility where they initially received emergency care. Main Outcomes and Measures The primary outcome of interest was surgical disease complexity at the time of presentation to emergency care. Secondary outcomes included inpatient complications, mortality, and indicators of health system resource utilization. Multivariable logistic regression models were used, and adjusted odds ratios (aOR) and 95% CIs were reported. Results Among 190 311 adults with emergency general surgery conditions, 7138 (3.8%) lived further than 60 minutes from the facility where they sought emergency care. Longer travel times were associated with higher odds of complex disease presentation for travel time of more than 120 minutes vs 15 minutes or less (aOR, 1.28; 95% CI, 1.17-1.40). Patients with a travel time 60 minutes or more were more likely to require operative intervention (aOR, 1.17; 95% CI, 1.10-1.26), inpatient admission (aOR, 1.41; 95% CI, 1.33-1.50), interfacility transfer (aOR, 1.32; 95% CI, 1.15-1.51), and longer inpatient stay (adjusted mean difference, 0.47 days; 95% CI, 0.35-0.59), and had higher charges (adjusted mean difference, $8284; 95% CI, $5532-$11 035). Conclusions and Relevance In this cohort study of patients with emergency surgical conditions, travel time to emergency care was associated with markers of delayed presentation and increased facility resource utilization. As opposed to static measures, such as rurality, travel time may serve as a more useful metric to inform policy efforts aimed at preserving access to care amidst rural hospital closures and regionalization.
Contraceptive Prescribing Among People Treated for Opioid Use Disorder
Authors: Carrie E. Fry, Yixuan Li, Manuel Horta, Ashley A. Leech
Journal: JAMA Internal Medicine (2025)

This cross-sectional study examines prescription claims for contraceptives and medications for opioid use disorder among commercially insured women in the US from 2016 to 2021.
Effectiveness and Safety of Dupilumab for Prurigo Nodularis in China: A Multicentric and Observational Study
Authors: Zuotao Zhao, Xiaoting Song, Yuanyuan Shang, Lijuan Liu, Rui Zheng, Jianxin Xia, Qiang Liu, Guodong Hao, Jie Li, Songmei Geng, Jingang An, Qiang Wang, Xiaoyan Liu, Jianping Tang, Yizhu Xiao, Litao Zhang
Journal: Allergy (2025)

The efficacy and safety of dupilumab in patients with refractory prurigo nodularis (PN) is well established in clinical trials, but there is a lack of multicenter data regarding its effectiveness and safety in real-world settings. Patients with moderate-to-severe PN who initiated dupilumab treatment between July 2023 and January 2024, with a follow-up period of at least 16 weeks at 10 hospitals in China were included. We used peak pruritus numeric rating scale (PP-NRS), investigator global assessment (IGA) for PN, and dermatology life quality index for adults or children (DLQI/CDLQI) to assess disease control status and quality of life impairment, and monitored adverse events to assess the safety. A total of 73 PN patients (33 female, 40 male; mean age 45.9 ± 21.5 years) were included. A clinically meaningful improvement of ≥ 4 points in PP-NRS (PP-NRS4) was achieved in 84.9% of patients at Week 12. The percentage of patients achieving IGA 0/1 significantly increasing from 0% to 37.0% and 46.6% at Week 12 and 16, respectively. Patient-reported quality of life outcomes showed substantial improvement, with decreasing from 16.6 ± 6.8 at baseline to 7.2 ± 4.9 at Week 12, 6.4 ± 4.5 at Week 16. The safety profile of dupilumab was favorable, with one patient reporting dry eyes. Dupilumab can effectively improve the pruritus, nodular lesions and quality of life for PN in real-world settings.
Inhibition of DEK restores hematopoietic stem cell function in Fanconi anemia
Authors: Zhe Chen, Feng Wu, Yan Li, Lei Li, Yufei Lei, Siwei Gao, Tao Chen, Yuxin Xie, Jianwen Xiao, Hanqing Zeng, Jianchuan Deng, Xueya Zhao, Yu Hou
Journal: The Journal of Experimental Medicine (2025)

Hematopoietic stem cells (HSCs) are susceptible to replication stress, which is a major contributor to HSC defects in Fanconi anemia (FA). Here, we report that HSCs relax the global chromatin by downregulating the expression of a chromatin architectural protein, DEK, in response to replication stress. DEK is abnormally accumulated in bone marrow (BM) CD34+ cells from patients with FA and in Fancd2-deficient HSCs. DEK haploinsufficiency promotes chromatin relaxation, replication stress relief, and function recovery of Fancd2-deficient HSCs. Furthermore, inhibition of DEK restores the proliferation of FA CD34+ cells in vitro and enhances their engraftment in vivo. Mechanistically, the activating transcription factor 2 (ATF2), specifically phosphorylated ATF2 at Thr69/71, was identified as a promoter of DEK transcription. Fancd2 deficiency results in p38 hyperphosphorylation, which in turn phosphorylates ATF2 at Thr69/71, leading to DEK accumulation in HSCs. In conclusion, our findings establish a functional link between chromatin relaxation and replication stress tolerance in HSCs and highlight DEK as a target for FA.
Bone-Induced Her2 Promotes Secondary Metastasis in HR+/Her2- Breast Cancer
Authors: Rahat Alam, Anna Reva, David G. Edwards, Bree M. Lege, Laura S. Munoz-Arcos, Carolina Reduzzi, Swarnima Singh, Xiaoxin Hao, Yi-Hsuan Wu, Zeru Tian, Laura M. Natalee, Gargi Damle, Deniz Demircioglu, Yixian Wang, Ling Wu, Elisabetta Molteni, Dan Hasson, Bora Lim, Zbigniew Gugala, Jerry E. Chipuk, Julie E. Lang, Joseph A. Sparano, Chonghui Cheng, Massimo Cristofanilli, Han Xiao, Xiang H.-F. Zhang, Igor L. Bado
Journal: Cancer Discovery (2025)

Abstract Bone metastases can disseminate to secondary sites and promote breast cancer progression creating additional clinical challenges. The mechanisms contributing to secondary metastasis are barely understood. Here, we evaluate the prediction power of Her2-expressing (Her2E) circulating tumor cells (CTCs) after analyzing over 13,000 CTCs from a cohort of 137 metastatic breast cancer (MBC) patients with initial HR+/Her2- status and employ preclinical models of bone metastasis (BM) to validate the role of Her2E CTCs in multi-organ metastases. While Her2 expression was higher in patients with bone metastasis, experimental analyses revealed that Her2E CTCs derived from bone lesions were more dependent on Her2 activity and more susceptible to anti-Her2 therapy. Targeting the bone-mediated Her2 induction reduces CTC detection and abrogates secondary metastasis from bone. Overall, we elucidate that Her2E CTCs can serve as a non-invasive biomarker for BM formation with high therapeutic benefit for HR+ MBC patients.
Metacognition in the listening brain
Authors: Jonas Obleser
Journal: Trends in Neurosciences (2025)

How do you know you have heard right? Metacognition, the ability to assess and monitor one's own cognitive state, is key to understanding human communication in complex environments. However, the foundational role of metacognition in hearing and communication is only beginning to be explored, and the neuroscience behind it is an emerging field: how does confidence express in neural dynamics of the listening brain? What is known about auditory metaperceptual alterations as a hallmark phenomenon in psychosis, dementia, or hearing loss? Building on Bayesian ideas of auditory perception and auditory neuroscience, 'meta-listening' offers a framework for more comprehensive research into how metacognition in humans and non-humans shapes the listening brain.
Elucidating hemodynamics and neuro-glio-vascular signaling using rodent fMRI
Authors: Xiaoqing Alice Zhou, Yuanyuan Jiang, Lidia Gomez-Cid, Xin Yu
Journal: Trends in Neurosciences (2025)

Despite extensive functional mapping studies using rodent functional magnetic resonance imaging (fMRI), interpreting the fMRI signals in relation to their neuronal origins remains challenging due to the hemodynamic nature of the response. Ultra high-resolution rodent fMRI, beyond merely enhancing spatial specificity, has revealed vessel-specific hemodynamic responses, highlighting the distinct contributions of intracortical arterioles and venules to fMRI signals. This 'single-vessel' fMRI approach shifts the paradigm of rodent fMRI, enabling its integration with other neuroimaging modalities to investigate neuro-glio-vascular (NGV) signaling underlying a variety of brain dynamics. Here, we review the emerging trend of combining multimodal fMRI with opto/chemogenetic neuromodulation and genetically encoded biosensors for cellular and circuit-specific recording, offering unprecedented opportunities for cross-scale brain dynamic mapping in rodent models.
Leveraging community engagement to shape biomedical research priorities
Authors: Sara Suliman, Lillian Agyei, Shaista A Afzal, Shanell Williams
Journal: Trends in Immunology (2025)

Community engagement is essential for shaping equitable biomedical research priorities, but it is often underutilized, especially for marginalized populations. To integrate community feedback from the public into research, herein we describe a collaborative pilot funded by the Chan Zuckerberg Initiative which pairs the University of California San Francisco (UCSF) with the Rafiki Coalition for Health and Wellness. Utilizing focus groups modeled on Research Prioritization by Affected Communities, participants identified themes that included mistrust in healthcare, representation gaps, and the need for culturally responsive research. Priorities such as mental health, chronic disease, and access to black providers were highlighted. The findings emphasize the need for sustained, grassroots partnerships to drive inclusive research agendas.
Shared selection and genetic architecture drive strikingly repeatable evolution in long-term experimental hybrid populations
Authors: Gregory L Owens, Celine Caseys, Nora Mitchell, Sariel Hübner, Kenneth D Whitney, Loren H Rieseberg
Journal: Molecular Biology and Evolution (2025)

Abstract The degree to which evolution repeats itself has implications regarding the major forces driving evolution and the potential for evolutionary biology to be a predictive (versus solely historical) science. To understand the factors that control evolutionary repeatability, we experimentally evolved four replicate hybrid populations of sunflowers at natural sites for up to 14 years and tracked ancestry across the genome. We found that there was very strong negative selection against introgressed ancestry in several chromosomes, but positive selection for introgressed ancestry in one chromosome. Further, the strength of selection was influenced by recombination rate. High recombination regions had lower selection against introgressed ancestry due to more frequent recombination away from incompatible backgrounds. Strikingly, evolution was highly parallel across replicates, with shared selection driving 88% of variance in introgressed allele frequency change. Parallel evolution was driven by both high levels of sustained linkage in introgressed alleles and strong selection on large-effect quantitative trait loci. This work highlights the repeatability of evolution through hybridization and confirms the central roles that natural selection, genomic architecture, and recombination play in the process.
Deciphering Plant NLR Genomic Evolution: Synteny-Informed Classification Unveils Insights into TNL Gene Loss
Authors: Bo-Cheng Guo, Yi-Rong Zhang, Zhi-Guang Liu, Xin-Chu Li, Ze Yu, Bo-Ya Ping, Ya-Qiang Sun, Harrold van den Burg, Feng-Wang Ma, Tao Zhao
Journal: Molecular Biology and Evolution (2025)

Abstract Nucleotide-binding leucine-rich repeat receptor (NLR) genes encode a pivotal class of plant immune receptors. However, their rampant duplication and loss have made inferring their genomic evolutionary trajectory difficult, exemplified by the loss of TNL family genes in monocots. In this study, we introduce a novel classification system for angiosperm NLR genes, grounded in network analysis of micro-synteny information. This refined classification categorizes these genes into five classes: CNL_A, CNL_B, CNL_C, TNL, and RNL. Compared to the previous classification, we further subdivided CNLs into three subclasses. The credibility of this classification is supported by phylogenetic analysis and examination of protein domain structures. Importantly, this classification enabled a model to explain the extinction of TNL genes in monocots. Compelling micro-synteny evidence underscores this revelation, indicating a clear synteny correspondence between the non-TNLs in monocots and the extinct TNL subclass. Our study provides crucial insights into the genomic origin and divergence of plant NLR subfamilies, unveiling the malleability-driven journey that has shaped the functionality and diversity of plant NLR genes.
MaveDB 2024: a curated community database with over seven million variant effects from multiplexed functional assays
Authors: Alan F. Rubin, Jeremy Stone, Aisha Haley Bianchi, Benjamin J. Capodanno, Estelle Y. Da, Mafalda Dias, Daniel Esposito, Jonathan Frazer, Yunfan Fu, Sally B. Grindstaff, Matthew R. Harrington, Iris Li, Abbye E. McEwen, Joseph K. Min, Nick Moore, Olivia G. Moscatelli, Jesslyn Ong, Polina V. Polunina, Joshua E. Rollins, Nathan J. Rollins, Ashley E. Snyder, Amy Tam, Matthew J. Wakefield, Shenyi Sunny Ye, Lea M. Starita, Vanessa L. Bryant, Debora S. Marks, Douglas M. Fowler
Journal: Genome biology (2025)

Abstract Multiplexed assays of variant effect (MAVEs) are a critical tool for researchers and clinicians to understand genetic variants. Here we describe the 2024 update to MaveDB ( https://www.mavedb.org/ ) with four key improvements to the MAVE community’s database of record: more available data including over 7 million variant effect measurements, an improved data model supporting assays such as saturation genome editing, new built-in exploration and visualization tools, and powerful APIs for data federation and streamlined submission and access. Together these changes support MaveDB’s role as a hub for the analysis and dissemination of MAVEs now and into the future.
Viremic non-progression in HIV/SIV infection: A tied game between virus and host
Authors: Ángel Bayón-Gil, Javier Martinez-Picado, Maria C Puertas
Journal: Cell Reports Medicine (2025)

High-efficacy antiretroviral treatment (ART) has been a game-changer for HIV/AIDS pandemic, but incomplete CD4+ T cell recovery and persistent chronic immune activation still affect HIV-suppressed people. Exceptional cases of HIV infection that naturally exhibit delayed disease progression provide invaluable insights into protective biological mechanisms with potential clinical application. Viremic non-progressors (VNPs) represent an extremely rare population of individuals with HIV, characterized by preservation of the CD4+ T cell compartment despite persistent high levels of viral load (>10,000 copies/mL). While only a few studies have investigated the immunovirological characteristics of adult and pediatric VNPs, most of our knowledge about this phenotype stems from its non-human-primate counterpart, the natural simian immunodeficiency virus (SIV) hosts. In this review, we synthesize the insights gained from recent studies of natural SIV hosts and VNPs and evaluate the potential similarities and differences in the mechanisms that underlie the absence of pathogenesis, with special focus on the control of immune activation.