tbuckley/cabot-search huggingface dataset:
Wealth Disparities in End-of-Life Symptom Burden Among Older Adults
Authors: Irena Cenzer, Kenneth E. Covinsky, Sarah H. Cross, Claire K. Ankuda, Lauren J. Hunt, Melissa D. Aldridge, Krista L. Harrison
Journal: JAMA Network Open (2025)

Understanding how wealth influences the end-of-life experience is crucial for improving patient care and policy, particularly with regard to symptom burden. To examine the prevalence of 12 end-of-life symptoms by wealth categories; the association between wealth and a composite measure of high symptom burden; and whether this association is mediated by multimorbidity, functional impairment, or dementia. This cohort study used data from the Health and Retirement Study (HRS), a nationally representative survey of older adults in the US, on decedents who died between January 1, 2000, and February 28, 2021, from proxy-reported exit interviews through February 28, 2021. Decedents were HRS participants aged 65 years or older who had completed a core interview within 24 months before death and had a proxy-reported exit interview. The data analysis was performed from October 6, 2023, through November 26, 2024. Wealth (assets opposed to income) was categorized into low (bottom quartile, <$6000), medium (middle 2 quartiles, $6000-$120 000), and high (top quartile, >$120 000). The presence of 12 individual end-of-life symptoms and a composite measure of high symptom burden (≥7 symptoms) were analyzed using modified Poisson regression. Mediators included multimorbidity, functional impairment, and dementia. Models were adjusted for age, sex, marital status, race and ethnicity, education, childhood socioeconomic status, HRS proxy respondent relationship, location of death, survey timing, year of death, and private insurance. Of 8976 decedents (mean [SD] age, 81.3 [8.6] years; 4927 women [55.1%] women) in the cohort, 2197 (22.5%) were included in the low wealth category, 4534 (50.5%) in the medium wealth category, and 2245 (27.1%) in the high wealth category. Decedents with lower wealth had a higher prevalence of end-of-life symptoms. High symptom burden was most common in the low wealth group (800 decedents [37.0%]) vs the medium (1301 decedents [28.0%]) and high wealth (512 decedents [23.2%]) groups. Low wealth was associated with a significantly increased risk of high symptom burden vs medium wealth (adjusted risk ratio, 0.79; 95% CI, 0.73-0.87) and high wealth (adjusted risk ratio, 0.71; 95% CI, 0.63-0.79). Multimorbidity, functional impairment, and dementia were more common in the low wealth group and mediated this association, with functional impairment being the strongest mediator. This cohort study found that lower wealth was associated with a higher symptom burden at the end of life, mediated in part by higher rates of multimorbidity, functional impairment, and dementia. These findings highlight the need for policies and programs to support patients with lower financial resources to improve end-of-life experiences and mitigate wealth disparities.
Eating Disorders
Authors: Evelyn Attia, B. Timothy Walsh
Journal: JAMA (2025)

Eating disorders are characterized by disturbances in eating behavior and occur worldwide, with a lifetime prevalence of 2% to 5%. They are more common among females than males and may be associated with medical and psychiatric complications, impaired functioning, and decreased quality of life. Common eating disorders include anorexia nervosa, bulimia nervosa, binge-eating disorder, and avoidant/restrictive food intake disorder. These disorders may be associated with changes in weight, electrolyte abnormalities (eg, hyponatremia, hypokalemia), bradycardia, disturbances in reproductive hormones (eg, decreased estradiol levels in females), and decreased bone density. Individuals with anorexia nervosa, bulimia nervosa, and binge-eating disorder have high lifetime rates of depression (76.3% for bulimia nervosa, 65.5% for binge-eating disorder, and 49.5% for anorexia nervosa) and higher rates of suicide attempts than those without eating disorders. Anorexia nervosa is associated with a mortality rate of 5.1 deaths per 1000 person-years (95% CI, 4.0-6.1), nearly 6 times higher than that of individuals of the same age without anorexia nervosa; 25% of deaths among individuals with anorexia nervosa are from suicide. First-line treatments for eating disorders include nutritional support, psychotherapy, and pharmacotherapy. Behaviorally focused therapies, including cognitive behavioral therapy, may be effective, especially for bulimia nervosa and binge-eating disorder. Youth with anorexia nervosa benefit from family-based treatment with parental oversight of eating, resulting in a remission rate at 6 to 12 months of 48.6% vs 34.3% with individual treatment (odds ratio, 2.08; 95% CI, 1.07-4.03; P = .03). Fluoxetine and other antidepressants decrease episodes of binge eating in individuals with bulimia nervosa, even in those without depression (fluoxetine vs placebo, standardized mean difference = -0.24 [small effect size; 95% CI, -0.41 to -0.08]). Antidepressants and the central nervous system stimulant lisdexamfetamine reduce binge frequency in binge-eating disorder compared with placebo (antidepressants vs placebo, standardized mean difference = -0.29 [small effect size; 95% CI, -0.51 to -0.06]; lisdexamfetamine vs placebo, Hedges g = 0.57 [medium effect size; 95% CI, 0.28-0.86]). There are currently no effective medications for treatment of anorexia nervosa. Individuals with serious medical or psychiatric complications of eating disorders such as bradycardia or suicidality should be hospitalized for treatment. Globally, eating disorders affect 2% to 5% of individuals during their lifetime and are more common in females than males. In addition to weight changes, eating disorders may cause electrolyte abnormalities, bradycardia, disturbances in reproductive hormones, and decreased bone density, and are associated with increased risk of depression, anxiety, and suicide attempts. First-line treatments of eating disorders include nutritional support, psychotherapy, and pharmacotherapy.
Implementing Social Determinants of Health Screening in US Emergency Departments
Authors: Stephanie Loo, Melanie Molina, N. Jia Ahmad, Maeve Swanton, Olivia Chen, Krislyn M. Boggs, Carlos A. Camargo, Margaret Samuels-Kalow
Journal: JAMA Network Open (2025)

Screening for adverse social determinants of health (SDOH) in the emergency department (ED) may help reduce health disparities in underserved populations. To understand barriers and facilitators to screening, documenting, and addressing adverse SDOH in a diverse sample of US EDs. This qualitative study used in-depth interviews with leaders of a purposive sample of EDs across urban, rural, academic, and community settings who self-reported screening for adverse SDOH on a prior National Emergency Department Inventory (NEDI) USA survey. EDs that completed the 2022 NEDI-USA survey and reported adverse SDOH screening were eligible for recruitment. Eligible participants were interviewed in April to September 2023. Inductive thematic analysis was conducted from September 2023 to January 2024 to identify themes and concepts. Themes and concepts related to ED practices for adverse SDOH screening and referral. From 77 eligible EDs, 27 leaders agreed to be interviewed, (18 [66.7%] female; mean [range] age, 44 [30 to 63] years; mean [range] time in current role, 3.25 [<1 to 12] years). Participants worked in a variety of leadership roles (eg, chair or medical, nursing, or operations director). Findings centered around heterogeneity in ED adverse SDOH screening and documentation practices; skepticism of utility of ED adverse SDOH screening and referral; drivers of ED adverse SDOH screening, such as regulatory mandates for the expansion of adverse SDOH screening; resource, staffing, and time constraints in adverse SDOH screening and linkage to services processes; and recommendations and suggestions for improving the implementation of ED adverse SDOH screening, such as tailoring validated tools to the ED context and ED stakeholder engagement in designing the screening process. Other suggestions included having additional dedicated screening staff, particularly social workers, and strengthening relationships with existing non-ED SDOH initiatives and community resources dedicated to addressing adverse SDOH. This qualitative study of US EDs describes an overview of practices and challenges surrounding adverse SDOH screening and identified novel solutions and areas where more research is needed for the successful implementation of adverse SDOH screening in the ED setting. At the policy level, regulatory mandates instituting adverse SDOH screening should include provisions for funding to support patient needs identified by screening. Additional research on development and implementation of ED adverse SDOH screening programs is needed.
Hypoxia inducible factor-1α drives cancer resistance to cuproptosis
Authors: Zhou Yang, Wei Su, Xiyi Wei, Yitong Pan, Mengying Xing, Lili Niu, Baijie Feng, Weiyu Kong, Xiaohan Ren, Feng Huang, Jingwan Zhou, Wei Zhao, Yingyi Qiu, Tian Liao, Qi Chen, Shuang Qu, Yunjun Wang, Qing Guan, Duanshu Li, Ke Zen, Yun Chen, Chao Qin, Yu Wang, Xiang Zhou, Jun Xiang, Bing Yao
Journal: Cancer Cell (2025)
Divergent populations of HIV-infected naïve and memory CD4+ T-cell clones in children on antiretroviral therapy
Authors: Mary Grace Katusiime, Victoria Neer, Shuang Guo, Sean C. Patro, Wenjie Wang, Brian Luke, Adam A. Capoferri, Xiaolin Wu, Anna M. Horner, Jason W. Rausch, Ann Chahroudi, Maud Mavigner, Mary F. Kearney
Journal: Journal of Clinical Investigation (2025)

Naïve cells comprise 90% of the CD4+ T-cell population in neonates and exhibit distinct age-specific capacities for proliferation and activation. We hypothesized that HIV-infected naïve CD4+ T-cell populations in children on long-term antiretroviral therapy (ART) would thus be distinct from infected memory cells. Peripheral blood naïve and memory CD4+ T cells from 8 children with perinatal HIV on ART initiated at age 1.7-17 months were isolated by FACS. DNA was extracted from sorted cells and HIV proviruses counted, evaluated for intactness, and subjected to integration site analysis. Naïve CD4+ T cells containing HIV proviruses were detected in children with 95% statistical confidence. A median of 4.7% of LTR-containing naïve CD4+ T cells also contained HIV genetic elements consistent with intactness. Full-length proviral sequencing confirmed intactness of one provirus. In the participant with the greatest level of naïve cell infection, ISA revealed infected expanded cell clones in both naïve and memory T cells with no common HIV integration sites detected between subsets. Divergent integration site profiles reflected differential gene expression patterns of naïve and memory T cells. These results demonstrate that HIV persists in both naïve and memory CD4+ T cells that undergo clonal expansion and harbor intact proviruses, suggesting that infected memory T-cell clones do not frequently arise from naïve cell differentiation in children with perinatal HIV on long-term ART. Center for Cancer Research, NCI and Office of AIDS Research funding to MFK, NCI FLEX funding to JWR. Children's and Emory JFF pilot to MM.
Fragmentomics profiling and quantification of plasma Epstein-Barr virus DNA enhance prediction of future nasopharyngeal carcinoma
Authors: W K Jacky Lam, Guannan Kang, Charles M L Chan, Vicky C T Lee, Mary-Jane L Ma, Qing Zhou, Peiyong Jiang, Irene O L Tse, Ann D King, Kenneth C W Wong, Edwin P Hui, Brigette B Y Ma, Anthony T C Chan, K C Allen Chan, Y M Dennis Lo
Journal: Cancer Cell (2025)

Fragmentomics analysis of plasma autosomal DNA has shown promise in cancer diagnostics. Here we evaluated the clinical utility of plasma Epstein-Barr virus (EBV) DNA fragmentomics analysis for nasopharyngeal carcinoma (NPC) screening. Among our prospective cohort of approximately 20,000 subjects that underwent two rounds of screening, we analyzed the first-round blood samples of subjects who tested positive for EBV DNA via polymerase chain reaction (PCR) (n = 558). We found that those who subsequently developed NPC in the second round exhibited a distinctive mononucleosomal size pattern, an NPC-associated end motif (specifically, a depletion of CC-motif) and aberrations in methylation identified through fragmentomics-based methylation analysis (FRAGMA). Subjects with these aberrant fragmentomics features and higher quantity of EBV DNA had a relative risk of 87.1 times greater for developing NPC in the second round compared to subjects tested negative for EBV DNA on PCR. These results demonstrate plasma DNA fragmentomics could predict future cancer risk.
Epigenomic State Transitions Characterize Tumor Progression in Mouse Lung Adenocarcinoma
Authors: Lindsay M. LaFave, Vinay K. Kartha, Sai Ma, Kevin Meli, Isabella Del Priore, Caleb Lareau, Santiago Naranjo, Peter M.K. Westcott, Fabiana M. Duarte, Venkat Sankar, Zachary Chiang, Alison Brack, Travis Law, Haley Hauck, Annalisa Okimoto, Aviv Regev, Jason D. Buenrostro, Tyler Jacks
Journal: Cancer Cell (2025)
Self-assembled patient-derived tumor-like cell clusters for personalized drug testing in diverse sarcomas
Authors: Tian Gao, Xinyu He, Junyi Wang, Jiayong Liu, Xiongbing Hu, Chujie Bai, Shenyi Yin, Yunfei Shi, Yanmin Wang, Zhichao Tan, Fang Cao, Shu Li, Yan-Jie Shi, Ruifeng Xue, Juan Li, Yang He, Jiaxin Li, Huinan Lu, Hanshuo Zhang, Lu Zhang, Zhiwei Fang, Xinyu Wang, Mengmeng Liu, Wenjun Fu, Lei Tang, Buqing Ye, Zhengfu Fan, Jianzhong Jeff Xi
Journal: Cell Reports Medicine (2025)

Several patient-derived tumor models have emerged recently. However, soft tissue sarcomas (STSs) present a challenge in developing preclinical drug-testing models due to their non-epithelial and complex nature. Here, we report a model termed patient-derived tumor-like cell clusters (PTCs) derived from STS patients. PTCs result from the self-assembly and proliferation of mesenchymal stem cells (MSCs), epithelial cells, and immune cells, faithfully recapitulating the morphology and function of the original tumors. Through standardized culture and drug-response assessment protocols, PTCs facilitate personalized drug testing, evaluating hundreds of therapies within two weeks. Notably, PTCs exhibit 100% accuracy in distinguishing between complete or partial response and disease progression. We demonstrate the utility of PTCs in guiding chemotherapy selection for a patient with relapse and metastases following conventional therapy, who exhibited a positive response after non-conventional therapy identified through PTC. These findings underscore the potential of PTCs for prospective use in clinical decision-making regarding therapy selection.
Acute kidney injury triggers hypoxemia by lung intravascular neutrophil retention that reduces capillary blood flow
Authors: Yohei Komaru, Liang Ning, Carine Lama, Anusha Suresh, Eirini Kefaloyianni, Mark J. Miller, Shinichi Kawana, Hailey M. Shepherd, Wenjun Li, Daniel Kreisel, Andreas Herrlich
Journal: Journal of Clinical Investigation (2025)

Sterile acute kidney injury (AKI) is common in the clinic and frequently associated with unexplained hypoxemia that does not improve with dialysis. AKI induces remote lung inflammation with neutrophil recruitment in mice and humans, but which cellular cues establish neutrophilic inflammation and how it contributes to hypoxemia is not known. Here we report that AKI induces rapid intravascular neutrophil retention in lung alveolar capillaries without extravasation into tissue or alveoli, causing hypoxemia by reducing lung capillary blood flow in the absence of substantial lung interstitial or alveolar edema. In contrast to direct ischemic lung injury, lung neutrophil recruitment during remote lung inflammation did not require cues from intravascular non-classical monocytes or tissue-resident alveolar macrophages. Instead, lung neutrophil retention depended on neutrophil chemoattractant CXCL2 released by activated classical monocytes. Comparative single-cell RNA-sequencing analysis of direct and remote lung inflammation revealed that alveolar macrophages are highly activated and produce CXCL2 only in direct lung inflammation. Establishing a CXCL2 gradient into the alveolus by intratracheal CXCL2 administration during AKI-induced remote lung inflammation enabled neutrophils to extravasate. We thus discovered important differences in lung neutrophil recruitment in direct versus remote lung inflammation and identified lung capillary neutrophil retention that negatively affects oxygenation by causing a ventilation-perfusion mismatch as a driver of AKI-induced hypoxemia.
Lymph node macrophages drive immune tolerance and resistance to cancer therapy by induction of the immune-regulatory cytokine IL-33
Authors: Sara Lamorte, Rene Quevedo, Robbie Jin, Luke Neufeld, Zhe Qi Liu, M Teresa Ciudad, Sabelo Lukhele, Jessica Bruce, Shreya Mishra, Xin Zhang, Zaid Kamil Saeed, Hal Berman, Dana J Philpott, Stephen E Girardin, Shane Harding, David H Munn, Tak W Mak, Mikael C I Karlsson, David G Brooks, Tracy L McGaha
Journal: Cancer Cell (2025)
Phase 1 study of IMCnyeso, a T cell receptor bispecific ImmTAC targeting NY-ESO-1-expressing malignancies
Authors: Juanita S. Lopez, Mohammed Milhem, Marcus O. Butler, Fiona Thistlethwaite, Brian A. Van Tine, Sandra P. D’Angelo, Melissa L. Johnson, Takami Sato, Hendrik-Tobias Arkenau, Ramakrishna Edukulla, Jason Wustner, Shannon Marshall, Jordi Rodon
Journal: Cell Reports Medicine (2025)

IMCnyeso, an immune mobilizing monoclonal T cell receptor against cancer (ImmTAC) bispecific (New York esophageal squamous cell carcinoma [NY-ESO]×CD3) T cell engager, targets an NY-ESO-1/L-antigen family member-1 isoform A (LAGE-1A) peptide presented by histocompatibility leukocyte antigen (HLA)-A∗02:01. In this phase 1 study, 28 HLA-A∗02:01+ patients with advanced NY-ESO-1/LAGE-1A-positive advanced tumors (n = 28) receive IMCnyeso weekly intravenously (dose range: 3-300 μg; 7 dose-escalation cohorts). The primary objective is to identify the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D); additional objectives include preliminary anti-tumor activity, pharmacokinetics, immunogenicity, and pharmacodynamic changes. The study was terminated before fully enrolling dose escalation, and the MTD was not identified. There are no treatment-related discontinuations or deaths. The most common adverse events are grade 1/2 cytokine release syndrome and associated symptoms. Cytokine induction and transient lymphocyte count decreases are observed at doses 30-300 μg. At these doses, preliminary efficacy includes mixed response (2 patients) and a median overall survival of 12 months. IMCnyeso is well tolerated and, at doses ≥30 μg, induces pharmacodynamic changes consistent with T cell redirection. This study was registered at ClinicalTrials.gov (NCT03515551).
Deciphering immune predictors of immunotherapy response: A multiomics approach at the pan-cancer level
Authors: Xuexin Li, Lu Pan, Weiyuan Li, Bingyang Liu, Chunjie Xiao, Valerie Chew, Xuan Zhang, Wang Long, Florent Ginhoux, Joseph Loscalzo, Marcus Buggert, Xiaolu Zhang, Ren Sheng, Zhenning Wang
Journal: Cell Reports Medicine (2025)

Immune checkpoint blockade (ICB) therapy has transformed cancer treatment, yet many patients fail to respond. Employing single-cell multiomics, we unveil T cell dynamics influencing ICB response across 480 pan-cancer and 27 normal tissue samples. We identify four immunotherapy response-associated T cells (IRATs) linked to responsiveness or resistance and analyze their pseudotemporal patterns, regulatory mechanisms, and T cell receptor clonal expansion profiles specific to each response. Notably, transforming growth factor β1 (TGF-β1)+ CD4+ and Temra CD8+ T cells negatively correlate with therapy response, in stark contrast to the positive response associated with CXCL13+ CD4+ and CD8+ T cells. Validation with a cohort of 23 colorectal cancer (CRC) samples confirms the significant impact of TGF-β1+ CD4+ and CXCL13+ CD4+ and CD8+ T cells on ICB efficacy. Our study highlights the effectiveness of single-cell multiomics in pinpointing immune markers predictive of immunotherapy outcomes, providing an important resource for crafting targeted immunotherapies for successful ICB treatment across cancers.
The night’s watch: Exploring how sleep protects against neurodegeneration
Authors: Samira Parhizkar, David M. Holtzman
Journal: Neuron (2025)

Sleep loss is often regarded as an early manifestation of neurodegenerative diseases given its common occurrence and link to cognitive dysfunction. However, the precise mechanisms by which sleep disturbances contribute to neurodegeneration are not fully understood, nor is it clear why some individuals are more susceptible to these effects than others. This review addresses critical unanswered questions in the field, including whether sleep disturbances precede or result from neurodegenerative diseases, the functional significance of sleep changes during the preclinical disease phase, and the potential role of sleep homeostasis as an adaptive mechanism enhancing resilience against cognitive decline and neurodegeneration.
Type I interferon exposure of an implantation-on-a-chip device alters invasive extravillous trophoblast function
Authors: Michael K Simoni, Seble G Negatu, Ju Young Park, Sneha Mani, Montserrat C Arreguin, Kevin R Amses, Dan Dongeun Huh, Monica Mainigi, Kellie A Jurado
Journal: Cell Reports Medicine (2025)
A key role of PIEZO2 mechanosensitive ion channel in adipose sensory innervation
Authors: Yu Wang, Yunxiao Zhang, Verina H Leung, Saba Heydari Seradj, Utku Sonmez, M Rocio Servin-Vences, Shuke Xiao, Xiangyu Ren, Leon Wang, Sassan A Mishkanian, Sejal A Kini, Jonathan Z Long, Darren J Lipomi, Li Ye, Ardem Patapoutian
Journal: Cell Metabolism (2025)

Compared with the well-established functions of sympathetic innervation, the role of sensory afferents in adipose tissues remains less understood. Recent work has revealed the anatomical and physiological significance of adipose sensory innervation; however, its molecular underpinning remains unclear. Here, using organ-targeted single-cell RNA sequencing, we identified the mechanoreceptor PIEZO2 as one of the most prevalent receptors in fat-innervating dorsal root ganglia (DRG) neurons. PIEZO2 deletion in fat-innervating neurons induced transcriptional programs in adipose tissue resembling sympathetic activation, mirroring DRG ablation. Conversely, a gain-of-function PIEZO2 mutant shifted the adipose phenotypes in the opposite direction. These results indicate that PIEZO2 plays a major role in the sensory regulation of adipose tissues. This discovery opens new avenues for exploring mechanosensation in organs not traditionally considered mechanically active, such as adipose tissues, and therefore sheds light on the broader significance of mechanosensation in regulating organ function and homeostasis.