tbuckley/cabot-search huggingface dataset:
CD44 in myEloid cells is a major driver of liver inflammation and injury in alcohol-related liver disease
Authors: Déborah Rousseau, Stéphanie Bonnafous, Frédéric Soysouvanh, Dorian Sarrail, Manon Bourinet, Axelle Strazzulla, Stéphanie Patouraux, Arnaud Borderie, Bastien Dolfi, Alexandre Gallerand, Marwin A Farrugia, Véronique Orian-rousseau, Yingzheng Xu, Jesse W. Williams, Stoyan Ivanov, Albert Tran, Rodolphe Anty, Carmelo Luci, Philippe Gual
Journal: Hepatology (2025)

Background and Aims: Alcohol-related liver disease (ALD) is one of the leading causes of severe liver disease with limited pharmacological treatments for alcohol-related steatohepatitis (ASH). CD44, a glycoprotein mainly expressed in immune cells, has been implicated in multiple inflammatory diseases but has never been studied in the ALD context. We therefore studied its contribution to ASH development in mice and its expression in ALD patients Approach and Results: Here, we report that liver CD44 expression is associated with liver injury and inflammation and its deficiency ( Cd44 -/- ) partially protected mice upon chronic plus binge ethanol feeding (CPB-EtOH). CD44 deletion in myeloid cells ( Cd44 myel-KO ) recapitulated the same protective effects associated with reduced inflammatory monocyte infiltration and neutrophil activation in the liver and diminished blood neutrophil-lymphocyte ratio (NLR). CD44-deficient neutrophils displayed reduced PMA-induced inflammatory mediator expression and increased phagocytosis of live bacteria. Cd44 myel-KO mice were also protected against hepatic steatosis mediated by CPB-EtOH or chronic ethanol feeding, due in part to increased SIRT1 mediated fatty acid beta-oxidation. CD44 neutralization with antibodies strongly decreased liver injury and inflammation (hepatic neutrophil frequency) and blood NLR upon CPB-EtOH. In samples from ALD patients, hepatic CD44 expression increased with ALD severity, correlated with hepatic TNFα and CD11b expression, and CD44-expressing neutrophils were enriched in alcohol-associated hepatitis. Conclusions: Human and experimental evidence supports CD44 as a marker of hepatic inflammation in ALD. In addition, CD44 modulates neutrophil mobilization and functions and its targeting partially prevents liver inflammation and injury in the context of acute-on-chronic alcohol drinking.
Genetically Reprogrammed Exosomes for Immunotherapy of Acute Myeloid Leukemia
Authors: Lei Zhang, Guoyun Kao, Yuanteng Zhao, Zeyu Zhang, Hyo Sun Kim, Xiaojing Shi, Qinqin Cheng, Tianling Hou, Heinz-Josef Lenz, Yong Zhang
Journal: Molecular Therapy (2025)
Can microbiota gut-brain axis reverse neurodegenerative disorders in human?
Authors: Yuan Xingxing, Serge Yannick Ouedraogo, Modou Lamin Jammeh, Lucette Simbiliyabo, John Nute Jabang, Mariam Jaw, Alansana Darboe, Yurong Tan, Ousman Bajinka
Journal: Ageing Research Reviews (2025)
Salvage Autologous Transplant in Relapsed Multiple Myeloma: Long-Term Follow-Up of the Phase 3 GMMG ReLApsE Trial
Authors: Marc-Andrea Baertsch, Jana Schlenzka, Thomas Hielscher, Marc S. Raab, Sandra Sauer, Maximilian Merz, Elias K Mai, Carsten Müller-Tidow, Steffen Luntz, Anna Jauch, Peter Brossart, Martin Goerner, Stefan Klein, Bertram Glass, Peter Reimer, Ullrich Graeven, Roland Fenk, Mathias Haenel, Ivana von Metzler, Hans-Walter Lindemann, Christof Scheid, Igor-Wolfgang W. Blau, Hans J Salwender, Richard Noppeney, Britta Besemer, Katja C. Weisel, Hartmut Goldschmidt
Journal: Blood (2025)

The multicenter, phase III GMMG ReLApsE trial (EudraCT-No:2009-013856-61) randomized relapsed and/or refractory multiple myeloma (RRMM) patients equally to lenalidomide/dexamethasone (LEN/DEX, 25mg days 1-21/40mg weekly, 4-week cycles) re-induction, salvage high dose chemotherapy (sHDCT, melphalan 200mg/m2), autologous stem cell transplantation (ASCT) and LEN maintenance (10mg/day; transplant arm, n=139) versus continuous LEN/DEX (control arm, n=138). Ninety-four percent of patients had received frontline HDCT/ASCT. We report an updated analysis of survival endpoints with a median follow-up of 99 months. Median progression-free survival (PFS) was 20.5 and 19.3 months in the transplant and control arm, respectively (HR 0.98; 95% CI 0.76-1.27; p=0.9). Median overall survival (OS) was 67.1 and 62.7 months (HR 0.89; 95% CI 0.66-1.20; p=0.44). Landmark analyses from sHDCT and the contemporaneous LEN/DEX cycle 5 were performed due to dropout of 29% of patients before sHDCT/ASCT in the transplant arm but did not reveal significant differences in PFS (23.0 vs. 20.3 months; HR 0.91; 95% CI 0.68-1.22; p=0.52) or OS (76.3 vs. 66.0 months; HR 0.8; 95% CI 0.56-1.13; p=0.2). Time to progression after frontline HDCT/ASCT (TTP1) was a prognostic factor but did not predict benefit from sHDCT/ASCT. The GMMG ReLApsE trial does not support use of sHDCT/ASCT in RRMM after frontline HDCT/ASCT. EudraCT-No: 2009-013856-61.
Screening for Osteoporosis to Prevent Fractures
Authors: Leila C. Kahwati, Christine E. Kistler, Graham Booth, Nila Sathe, Rachel D’Amico Gordon, Ebiere Okah, Roberta C. Wines, Meera Viswanathan
Journal: JAMA (2025)

Fragility fractures result in significant morbidity. To review evidence on osteoporosis screening to inform the US Preventive Services Task Force. PubMed, Embase, Cochrane Library, and trial registries through January 9, 2024; references, experts, and literature surveillance through July 31, 2024. Randomized clinical trials (RCTs) and systematic reviews of screening; pharmacotherapy studies for primary osteoporosis; predictive and diagnostic accuracy studies. Two reviewers assessed titles/abstracts, full-text articles, study quality, and extracted data; when at least 2 similar studies were available, meta-analyses were conducted. Hip, clinical vertebral, major osteoporotic, and total fractures; mortality; harms; accuracy. Three RCTs and 3 systematic reviews reported benefits of screening in older, higher-risk women. Two RCTs used 2-stage screening: Fracture Risk Assessment Tool estimate with bone mineral density (BMD) testing if risk threshold exceeded. One RCT used BMD plus additional tests. Screening was associated with reduced hip (pooled relative risk [RR], 0.83 [95% CI, 0.73-0.93]; 3 RCTs; 42 009 participants) and major osteoporotic fracture (pooled RR, 0.94 [95% CI, 0.88-0.99]; 3 RCTs; 42 009 participants) compared with usual care. Corresponding absolute risk differences were 5 to 6 fewer fractures per 1000 participants screened. The discriminative accuracy of risk assessment instruments to predict fracture or identify osteoporosis varied by instrument and fracture type; most had an area under the curve between 0.60 and 0.80 to predict major osteoporotic fracture, hip fracture, or both. Calibration outcomes were limited. Compared with placebo, bisphosphonates (pooled RR, 0.67 [95% CI, 0.45-1.00]; 6 RCTs; 12 055 participants) and denosumab (RR, 0.60 [95% CI, 0.37-0.97] from the largest RCT [7808 participants]) were associated with reduced hip fractures. Compared with placebo, no statistically significant associations were observed for adverse events. Screening in higher-risk women 65 years or older was associated with a small absolute risk reduction in hip and major fractures compared with usual care. No evidence evaluated screening with BMD alone or screening in men or younger women. Risk assessment instruments, BMD alone, or both have poor to modest discrimination for predicting fracture. Osteoporosis treatment with bisphosphonates or denosumab over several years was associated with fracture reductions and no meaningful increase in adverse events.
Screening for Osteoporosis to Prevent Fractures
Authors: Wanda K. Nicholson, Michael Silverstein, John B. Wong, David Chelmow, Tumaini Rucker Coker, Esa M. Davis, Carlos Roberto Jaén, Marie Krousel-Wood, Sei Lee, Li Li, Carol M. Mangione, Gbenga Ogedegbe, Goutham Rao, John M. Ruiz, James Stevermer, Joel Tsevat, Sandra Millon Underwood, Sarah Wiehe
Journal: JAMA (2025)

Osteoporotic fractures are associated with psychological distress, subsequent fractures, loss of independence, reduced ability to perform activities of daily living, and death. The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the evidence on the benefits and harms of screening for osteoporosis to prevent fractures in adults 40 years or older with no known diagnosis of osteoporosis or history of fragility fracture. Adults 40 years or older without known osteoporosis or history of fragility fractures. The USPSTF concludes with moderate certainty that screening for osteoporosis to prevent osteoporotic fractures in women 65 years or older has moderate net benefit. The USPSTF concludes with moderate certainty that screening for osteoporosis to prevent osteoporotic fractures in postmenopausal women younger than 65 years at increased risk has moderate net benefit. The USPSTF concludes that the evidence is insufficient and the balance of benefits and harms for screening for osteoporosis to prevent osteoporotic fractures in men cannot be determined. The USPSTF recommends screening for osteoporosis to prevent osteoporotic fractures in women 65 years or older. (B recommendation) The USPSTF recommends screening for osteoporosis to prevent osteoporotic fractures in postmenopausal women younger than 65 years who are at increased risk for an osteoporotic fracture as estimated by clinical risk assessment. (B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for osteoporosis to prevent osteoporotic fractures in men. (I statement).
Error in Results and Discussion
Journal: JAMA Network Open (2025)

In the Original Investigation titled "Patterns in California Ambulance Patient Offload Times by Local Emergency Medical Services Agency," 1 published December 16, 2024, the Results and Discussion incorrectly stated that among 13 emergency medical services agencies with an APOT-1 weighted mean of more than 30 minutes for all 3 years of the study period, 7 were among the top 10 APOT-1 weighted means for all 3 years; in reality, 8 of the 13 were among the top 10 for all 3 years.This article has been corrected. 1
Digital Meditation to Target Employee Stress
Authors: Rachel M. Radin, Julie Vacarro, Elena Fromer, Sarah E. Ahmadi, Joanna Y. Guan, Sarah M. Fisher, Sarah D. Pressman, John F. Hunter, Kate Sweeny, A. Janet Tomiyama, Lauren Tiongco Hofschneider, Matthew J. Zawadzki, Larisa Gavrilova, Elissa S. Epel, Aric A. Prather
Journal: JAMA Network Open (2025)

Importance Mindfulness meditation may improve well-being among employees; however, effects of digital meditation programs are poorly understood. Objective To evaluate the effects of digital meditation vs a waiting list condition on general and work-specific stress and whether greater engagement in the intervention moderates these effects. Design, Setting, and Participants This randomized clinical trial included a volunteer sample of adults (aged ≥18 years) employed at a large academic medical center who reported mild to moderate stress, had regular access to a web-connected device, and were fluent in English. Exclusion criteria included being a regular meditator. Participants were recruited from May 16, 2018, through September 28, 2019, and completed baseline, 8-week, and 4-month measures assessing stress, job strain, burnout, work engagement, mindfulness, depression, and anxiety. Data were analyzed from March 2023 to October 2024. Intervention Participants were randomized 1:1 to a digital meditation program or the waiting list control condition. Participants in the intervention group were instructed to complete 10 minutes of meditation per day for 8 weeks. The control group was instructed to continue their normal activities and not add any meditation during the study period. Main Outcomes and Measures The primary outcome measure was change in Perceived Stress Scale (PSS) score at 8 weeks. Secondary outcome measures included changes in job strain, measured as work effort-reward imbalance. Results A total of 1458 participants (mean [SD] age, 35.54 [10.30] years; 1178 [80.80%] female) were included. Those randomized to meditation (n = 728) vs waiting list (n = 730) showed improvements in PSS (Cohen d , 0.85; 95% CI, 0.73-0.96) and in all secondary outcome measures (eg, job strain: Cohen d , 0.34; 95% CI, 0.23-0.46) at 8 weeks. These improvements were maintained at 4 months after randomization (PSS: Cohen d , 0.71; 95% CI, 0.59-0.84; job strain: Cohen d , 0.37; 95% CI, 0.25-0.50). Those using the app from 5 to 9.9 min/d vs less than 5 min/d showed greater reduction in stress (mean PSS score difference, −6.58; 95% CI, −7.44 to −5.73). Conclusions and Relevance The findings suggest that a brief, digital mindfulness-based program is an easily accessible and scalable method for reducing perceptions of stress. Future work should seek to clarify mechanisms by which such interventions contribute to improvements in work-specific well-being. Trial Registration ClinicalTrials.gov Identifier: NCT03527303
Esophageal <i>Candida</i> Infection and Esophageal Cancer Risk in Patients With Achalasia
Authors: Xiaopei Guo, Suk Yee Lam, Vincent T. Janmaat, Pieter Jan F. de Jonge, Bettina E. Hansen, Ivonne Leeuwenburgh, Maikel P. Peppelenbosch, Manon C. W. Spaander, Gwenny M. Fuhler
Journal: JAMA Network Open (2025)

Patients with achalasia face a higher risk of developing esophageal cancer (EC), but the surveillance strategies for these patients remain controversial due to the long disease duration and the lack of identified risk factors. To investigate the prevalence of esophageal Candida infection among patients with achalasia and to assess the association of Candida infection with EC risk within this population. This retrospective cohort study included patients with achalasia diagnosed at or referred for treatment and monitoring to the Erasmus University Medical Center in Rotterdam, the Netherlands, between January 1, 1980, and May 31, 2024. Data analysis was conducted from August 1 to October 31, 2024. Esophageal Candida infection. The primary outcomes were the prevalence of esophageal Candida infection and its association with EC development among patients with achalasia. Associations were estimated using time-dependent Cox proportional hazards regression models with esophageal Candida infection as a time-varying covariate, adjusting for age at diagnosis and sex. This study included 234 patients with achalasia (median [IQR] age at diagnosis, 45 [32-63] years; 117 [50%] male), with a median follow-up time of 13 (4-22) years. Esophageal Candida infection was identified in 29 patients (12%), while EC was observed in 24 patients (10%). Esophageal cancer risk analysis was performed for 207 patients with 2 or more consecutive endoscopy follow-up visits (median [IQR] age at diagnosis, 43 [32-60] years; 104 [50%] male). The median (IQR) follow-up time for this subgroup was 16 (9-26) years. Among these patients, esophageal Candida infection was independently associated with an increased risk of EC (adjusted hazard ratio [AHR], 8.24 [95% CI, 2.97-22.89]). Additionally, age at diagnosis (AHR, 1.06 [95% CI, 1.03-1.10]) and male sex (AHR, 3.34 [95% CI, 1.08-10.36]) were independently associated with EC risk. This retrospective cohort study found that prior esophageal Candida infection, older age at diagnosis, and male sex were associated with increased risk of EC among patients with achalasia. These findings provide an important rationale for optimizing the monitoring of patients with achalasia.
Dopamine D1 receptor activation in the striatum is sufficient to drive reinforcement of anteceding cortical patterns
Authors: Nuria Vendrell-Llopis, Jonathan Read, Samantha Boggiano, Belinda Hetzler, Zisis Peitsinis, Cherise Stanley, Meike Visel, Dirk Trauner, Prashant Donthamsetti, Jose Carmena, Stephan Lammel, Ehud Y Isacoff
Journal: Neuron (2025)
Use and Costs of Supplemental Benefits in Medicare Advantage, 2017-2021
Authors: Christopher L. Cai, Sonia Iyengar, Steffie Woolhandler, David U. Himmelstein, Kavya Kannan, Lisa Simon
Journal: JAMA Network Open (2025)

Importance Nearly all Medicare Advantage (MA) plans offer dental, vision, and hearing benefits not covered by traditional Medicare (TM). However, little is known about MA enrollees’ use of those benefits or how much they cost MA insurers or enrollees. Objective To estimate use, out-of-pocket (OOP) spending, and insurer payments for dental, hearing, and vision services among Medicare beneficiaries. Design, Setting, and Participants This cross-sectional analysis used pooled 2017-2021 Medical Expenditure Panel Survey (MEPS) and Medicare Current Beneficiary Survey (MCBS) data for MA and TM beneficiaries (excluding those also covered by Medicaid). The analysis was performed from September 10, 2023, to June 30, 2024. Exposures MA compared with TM coverage. Main Outcomes and Measures The main outcome was receipt of eye examinations, corrective lenses, hearing aids, optometry and dental visits, and MA and TM enrollees’ and insurers’ spending for such services. MEPS and MCBS data were weighted to be nationally representative. Results We included 76 557 non–dually eligible Medicare beneficiaries, including 23 404 from the MEPS and 53 153 from the MCBS. Weighted demographic characteristics of MA and TM beneficiaries were similar (54.7% and 51.9% female; 39.8% and 35.2% older than 75 years, respectively). Only 54.2% (95% CI, 52.4%-55.9%) and 54.3% (95% CI 52.2%-56.3%) of MA beneficiaries were aware of having MA dental and vision coverage, respectively. MA enrollees were no more likely to receive eye examinations, hearing aids, or eyeglasses than TM enrollees. After adjustment for demographic differences, MA and TM enrollees paid OOP $205.86 (95% CI, $192.44-$219.27) and $226.12 (95% CI, $212.02-$240.23), respectively, for eyeglasses (MA − TM difference, −$20.27 [95% CI, −$33.77 to −$6.77] or −9.0% [95% CI, −14.9% to −3.0%]); $226.82 (95% CI, $202.24-$251.40) and $249.98 (95% CI, $226.22-$273.74) for dental visits, respectively (MA − TM difference, −$23.16 [95% CI, −$43.15 to −$3.17] or −9.3% [95% CI, −17.3% to −1.3%]); and no less for optometry visits or durable medical equipment (a proxy for hearing aids). Nationwide, MA plans’ annual spending on vision, dental services, and durable medical equipment totaled $3.9 billion (95% CI, $3.3-$4.4 billion), while enrollees spent OOP $9.2 billion (95% CI, $8.2-$10.2 billion) annually for these services and other private insurers covered $2.8 billion (95% CI, $2.7-$3.0 billion). Conclusions and Relevance In this cross-sectional study of 2 nationally representative surveys, MA beneficiaries did not receive more supplemental services than TM beneficiaries, possibly because of cost-sharing and limited awareness of benefit coverage.
TP53 germline testing and hereditary cancer: how somatic events and clinical criteria affect variant detection rate
Authors: Paula Rofes, Carmen Castillo-Manzano, Mireia Menéndez, Álex Teulé, Sílvia Iglesias, Elisabet Munté, Mireia Ramos-Muntada, Carolina Gómez, Eva Tornero, Esther Darder, Eva Montes, Laura Valle, Gabriel Capellá, Marta Pineda, Joan Brunet, Lidia Feliubadaló, Jesús del Valle, Conxi Lázaro
Journal: Genome Medicine (2025)
Preferred and Actual Location of Death in Adolescents and Young Adults With Cancer
Authors: Oreofe O. Odejide, Colin Cernik, Hajime Uno, Lauren Fisher, Lanfang Xu, Cecile A. Laurent, Nancy Cannizzaro, Julie Munneke, Robert M. Cooper, Joshua R. Lakin, Corey M. Schwartz, Mallory Casperson, Andrea Altschuler, Lori Wiener, Lawrence Kushi, Chun R. Chao, Jennifer W. Mack
Journal: JAMA Network Open (2025)

Importance Adolescent and young adult (AYA) patients with advanced cancer often die in hospital settings. Data characterizing the degree to which this pattern of care is concordant with patient goals are sparse. Objective To evaluate the extent of concordance between the preferred and actual location of death among AYA patients with cancer. Design, Setting, and Participants This multicenter retrospective cohort study included AYA patients (aged 12-39 years) with cancer who died between January 1, 2003, and December 31, 2019, after receiving care at Dana-Farber Cancer Institute and Kaiser Permanente Northern California or who died between January 1, 2009, and December 31, 2019, after receiving care at Kaiser Permanente Southern California. Data were analyzed from January 12 to July 1, 2024. Exposure Death due to cancer. Main Outcomes and Measures Medical record documentation of discussions about preferred location of death, actual location of death, and concordance between preferred and actual location of death. Results The analytic population included 1929 AYA decedents, of whom 1049 (54.4%) were female; 227 (11.8%), Asian; 157 (8.1%), Black; 514 (26.6%), Hispanic; and 1184 (61.4%), White. Median age at death was 32 (IQR, 25-37) years. A total of 1226 AYA patients (63.6%) had a documented discussion about preferred location of death. Among those with a documented discussion, 594 (48.5%) did not have a documented preference, 402 (32.8%) wanted to die at home, 177 (14.4%) preferred a hospital death, and 48 (3.9%) desired inpatient hospice. Eight hundred and thirty patients (43.0%) died in acute care settings (256 [13.3%] intensive care unit [ICU], 548 [28.4%] hospital [non-ICU], and 26 [1.3%] emergency department), while 643 (33.3%) died at home and 47 (2.4%) in an inpatient hospice. Among the 528 patients with both a documented preferred death location of home, hospital, or inpatient hospice and documented death in one of these locations, the concordance between preferred and actual location of death was 401 (75.9%). One hundred and sixty-four of 172 patients (95.3%) who preferred a hospital death died there; 224 of 317 (70.7%) who preferred a home death died at home, and 13 of 39 (33.3%) who desired to die in inpatient hospice did so. Conclusions and Relevance Although many AYA patients with cancer died in their preferred location, over one-quarter of those who desired to die at home did not realize this goal. These findings highlight the need for effective solutions to enable goal-concordant care for this population.
CRISPRi-based screens in iAssembloids to elucidate neuron-glia interactions
Authors: Emmy Li, Camila Benitez, Steven C Boggess, Mark Koontz, Indigo V L Rose, Delsy Martinez, Nina Dräger, Olivia M Teter, Avi J Samelson, Na'im Pierce, Erik M Ullian, Martin Kampmann
Journal: Neuron (2025)

The complexity of the human brain makes it challenging to understand the molecular mechanisms underlying brain function. Genome-wide association studies have uncovered variants associated with neurological phenotypes. Single-cell transcriptomics have provided descriptions of changes brain cells undergo during disease. However, these approaches do not establish molecular mechanism. To facilitate the scalable interrogation of causal molecular mechanisms in brain cell types, we developed a 3D co-culture system of induced pluripotent stem cell (iPSC)-derived neurons and glia, termed iAssembloids. Using iAssembloids, we ask how glial and neuronal cells interact to control neuronal death and survival. Our CRISPRi-based screens identified that GSK3β inhibits the protective NRF2-mediated oxidative stress response elicited by high neuronal activity. We then investigate the role of APOE-ε4, a risk variant for Alzheimer's disease, on neuronal survival. We find that APOE-ε4-expressing astrocytes may promote neuronal hyperactivity as compared with APOE-ε3-expressing astrocytes. This platform allows for the unbiased identification of mechanisms of neuron-glia cell interactions.
Maternal circadian rhythms during pregnancy dictate metabolic plasticity in offspring
Authors: Na Yao, Kenichiro Kinouchi, Manami Katoh, Kousha Changizi Ashtiani, Sherif Abdelkarim, Hiroyuki Morimoto, Takuto Torimitsu, Takahide Kozuma, Akihide Iwahara, Shotaro Kosugi, Jin Komuro, Kyosuke Kato, Shun Tonomura, Toshifumi Nakamura, Arata Itoh, Shintaro Yamaguchi, Jun Yoshino, Junichiro Irie, Hisayuki Hashimoto, Shinsuke Yuasa, Akiko Satoh, Yohei Mikami, Shusaku Uchida, Takatoshi Ueki, Seitaro Nomura, Pierre Baldi, Kaori Hayashi, Hiroshi Itoh
Journal: Cell Metabolism (2025)