tbuckley/cabot-search huggingface dataset:
The Role of Regional and Practice Trial Sites in Non-Representative Randomized Cancer Trial Enrollment
Authors: Sachin J Shah, Christopher R Manz, Brendan Balthis, Hari S Raman, Jason Abaluck, Nancy L Keating, Leila Agha
Journal: JNCI Journal of the National Cancer Institute (2025)

Representative trials are critical to advancing cancer treatment, yet little is known about how geographic siting contributes to non-representative enrollment. Using patient-level data, we determined how the choice of trial-enrolling regions and practices impacts representativeness. We created a SEER-Medicare cohort of people ≥65 years old with lung, breast, pancreatic, or renal cancer (2014-2019). We identified randomized cancer drug trial participants and determined the prevalence of age ≥75, sex, race, ethnicity, and rural residence in the full cohort, trial-enrolling regions, trial-enrolling practices, and trials. The choice of region and practice contributed to > 50% of the under-enrollment of Black, Hispanic, and rural patients. Cancer trials enrolled 45% fewer Black patients than expected with proportional representation. Trial recruitment in regions and practices with proportionately fewer Black patients accounted for 27% and 35% of this disparity, respectively. These findings suggest that diversifying cancer trials requires changing the regions and practices referring and enrolling patients.
Utilizing Patient Input in Rectal Cancer Trial Design
Authors: Janet Alvarez, Wini Zambare, Manju George, Reese Garcia, Phuong Gallagher, Caleah Kitchens, Aron Bercz, Min Jung Kim, Paul B Romesser, Andrea Cercek, Julio Garcia-Aguilar, Hanna Sanoff, Thomas J George, Theodore S Hong, Greg Yothers, Philip A Philip, Tareq Al Baghdadi, Olatunji B Alese, Ardaman Shergill, Eileen M O’Reilly, Jeffrey A Meyerhardt, Natally Horvat, Arvind Dasari, William A Hall, Qian Shi, Deborah Schrag, J Joshua Smith
Journal: JNCI Journal of the National Cancer Institute (2025)

The treatment of locally advanced rectal cancer now includes "watch-and-wait" (WW) management for patients who exhibit a clinical complete response (cCR) to total neoadjuvant therapy (TNT). We assessed patients' knowledge and preferences regarding WW with the goal of incorporating patient input into clinical trial design. Rectal cancer patients in advocacy groups (COLONTOWN/Rectalburgh and Fight CRC) were surveyed regarding perceptions about treatment strategies, tolerable risks of treatment failure, and preferences on clinical trial design. Surveys were initially distributed in 2019, with the shift toward WW prompting re-survey of select questions in 2023. All respondents preferred enrollment in trials that incorporated patient input. Most respondents (76%) preferred treatment that incorporated chemotherapy escalation over radiation escalation. Further, when presented with a hypothetical patient who developed a cCR after chemoradiation (without the option for WW), 58% of patients chose surgical treatment (with 100% risk of permanent ostomy and 80% chance of cure) over omission of surgery (with <80% chance of cure). In contrast, when the hypothetical patient developed a cCR after TNT (with an option for WW), 82% of patients opted for selective WW over surgery. This work successfully integrated patient advocacy groups as a resource for obtaining patient input. Surveys revealed patients had a strong preference for chemotherapy escalation, for selective WW when offered, and for incorporation of input into future clinical trial design. These findings describe how well-informed patients approach complex medical decision-making and serve as a starting point for future studies seeking to incorporate patient voices.
Area-level socioeconomic inequalities in activities of daily living disability-free life expectancy in England: a modelling study
Authors: Laurie E Davies, David R Sinclair, Christopher Todd, Barbara Hanratty, Fiona E Matthews, Andrew Kingston
Journal: The Lancet Healthy Longevity (2025)

More evidence of socioeconomic inequalities in disability-free life expectancy (DFLE) is needed to help develop approaches to narrow the gap between the most and least socioeconomically deprived people. Activities of daily living (ADL) disability represents the most severe and expensive disablement stage. Using combined longitudinal data, we aimed to quantify area-level socioeconomic inequalities in ADL-DFLE and the total person-years lived with ADL disability, in older men and women in England. In this modelling study, we harmonised data on ADL disability, area deprivation, age, and self-reported gender for individuals aged 50 years or older from three longitudinal studies in England: the English Longitudinal Study of Ageing (n=11 337), the Cognitive Function and Ageing Study II (n=7469), and the Newcastle 85+ Study (n=847). We used multistate modelling, and calculated the remaining life expectancy with and without ADL disability by gender and area-level socioeconomic status (<20%, 20-80%, and >80% of Index of Multiple Deprivation). From these data and Office for National Statistics population figures for the year 2024, we estimated the extra person-years lived with ADL disability by those aged 65 years from the most socioeconomically deprived areas. Those living in the least deprived areas had a reduced risk of ADL disability compared with those in the most deprived areas (hazard ratio [HR] 0·61 [95% CI 0·55-0·69]; p<0·0001), as did those in the middle area-level socioeconomic group (HR 0·76 [0·69-0·84]; p<0·0001). Increasing area-level socioeconomic disadvantage was associated with reduced life expectancy and more time spent with ADL disability, particularly for women. Living in the most disadvantaged areas was associated with people having ADL disability 11·0 years earlier for men and 12·0 years earlier for women, compared with living in the least deprived areas. An extra 59 000 person-years for men and 88 000 person-years for women were lived with ADL disability by those in the most deprived areas, at the population level, compared with the least deprived areas. Targeted policies to address underlying socioeconomic inequalities in health are likely to be the long-term definitive solution. National Institute for Health and Care Research Policy Research Unit in Healthy Ageing.
Direct-to-Physician Marketing and Uptake of Optimal Medical Therapy for Heart Failure With Reduced Ejection Fraction
Authors: Colette DeJong, Kosuke Inoue, Matthew S Durstenfeld, Anubha Agarwal, Justin C Chen, Chien-Wen Tseng, R Adams Dudley, Priscilla Y Hsue, Dhruv S Kazi
Journal: JACC Heart Failure (2025)
Credibility assessment of a mechanistic model of atherosclerosis to predict cardiovascular outcomes under lipid-lowering therapy
Authors: Yishu Wang, Eulalie Courcelles, Emmanuel Peyronnet, Solène Porte, Alizée Diatchenko, Evgueni Jacob, Denis Angoulvant, Pierre Amarenco, Franck Boccara, Bertrand Cariou, Guillaume Mahé, Philippe Gabriel Steg, Alexandre Bastien, Lolita Portal, Jean-Pierre Boissel, Solène Granjeon-Noriot, Emmanuelle Bechet
Journal: npj Digital Medicine (2025)

Demonstrating cardiovascular (CV) benefits with lipid-lowering therapy (LLT) requires long-term randomized clinical trials (RCTs) with thousands of patients. Innovative approaches such as in silico trials applying a disease computational model to virtual patients receiving multiple treatments offer a complementary approach to rapidly generate comparative effectiveness data. A mechanistic computational model of atherosclerotic cardiovascular disease (ASCVD) was built from knowledge, describing lipoprotein homeostasis, LLT effects, and the progression of atherosclerotic plaques leading to myocardial infarction, ischemic stroke, major acute limb event and CV death. The ASCVD model was successfully calibrated and validated, and reproduced LLT effects observed in selected RCTs (ORION-10 and FOURIER for calibration; ORION-11, ODYSSEY-OUTCOMES and FOURIER-OLE for validation) on lipoproteins and ASCVD event incidence at both population and subgroup levels. This enables the future use of the model to conduct the SIRIUS programme, which intends to predict CV event reduction with inclisiran, an siRNA targeting hepatic PCSK9 mRNA.
Development of an Electroconductive Heart-on-a-Chip Model to Investigate Cellular and Molecular Response of Human Cardiac Tissue to Gold Nanomaterials
Authors: Hamid Esmaeili, Yining Zhang, Kalpana Ravi, Keagan Neff, Wuqiang Zhu, Raymond Q Migrino, Jin G Park, Mehdi Nikkhah
Journal: Biomaterials (2025)
Endogenous dual-responsive and self-adaptive silk fibroin-based scaffold with enhancement of immunomodulation for skull regeneration
Authors: Xuewei Bi, Zhinan Mao, Yilin Zhang, Zeqi Ren, Kang Yang, Chunhao Yu, Lei Chen, Rui Zheng, Juan Guan, Zhenhai Liu, Binsheng Yu, Yongcan Huang, Xiong Shu, Yufeng Zheng
Journal: Biomaterials (2025)
Cross sectional pilot study on clinical review generation using large language models
Authors: Zining Luo, Yang Qiao, Xinyu Xu, Xiangyu Li, Mengyan Xiao, Aijia Kang, Dunrui Wang, Yueshan Pang, Xing Xie, Sijun Xie, Dachen Luo, Xuefeng Ding, Zhenglong Liu, Ying Liu, Aimin Hu, Yixing Ren, Jiebin Xie
Journal: npj Digital Medicine (2025)

As the volume of medical literature accelerates, necessitating efficient tools to synthesize evidence for clinical practice and research, the interest in leveraging large language models (LLMs) for generating clinical reviews has surged. However, there are significant concerns regarding the reliability associated with integrating LLMs into the clinical review process. This study presents a systematic comparison between LLM-generated and human-authored clinical reviews, revealing that while AI can quickly produce reviews, it often has fewer references, less comprehensive insights, and lower logical consistency while exhibiting lower authenticity and accuracy in their citations. Additionally, a higher proportion of its references are from lower-tier journals. Moreover, the study uncovers a concerning inefficiency in current detection systems for identifying AI-generated content, suggesting a need for more advanced checking systems and a stronger ethical framework to ensure academic transparency. Addressing these challenges is vital for the responsible integration of LLMs into clinical research.
Correction: WT1-mRNA dendritic cell vaccination of patients with glioblastoma multiforme, malignant pleural mesothelioma, metastatic breast cancer, and other solid tumors: type 1 T-lymphocyte responses are associated with clinical outcome
Authors: Zwi N. Berneman, Maxime De Laere, Paul Germonpré, Manon T. Huizing, Yannick Willemen, Eva Lion, Hans De Reu, Jolien Van den Bossche, Jan Van den Brande, Pol Specenier, Sevilay Altintas, Peter A. van Dam, Nathalie Cools, Griet Nijs, Barbara Stein, Kim Caluwaerts, Annemiek Snoeckx, Bart Op de Beeck, Kirsten Saevels, Lynn Rutsaert, Irma Vandenbosch, Gizem Oner, Martin Lammens, Pierre Van Damme, Sian Llewellyn-Lacey, David A. Price, Yoshihiro Oka, Yusuke Oji, Haruo Sugiyama, Marie M. Couttenye, Ann L. Van de Velde, Viggo F. Van Tendeloo, Marc Peeters, Sébastien Anguille, Evelien L. J. M. Smits
Journal: Journal of Hematology & Oncology (2025)
HemAtlas: A Multi-omics Hematopoiesis Database
Authors: Zhixin Kang, Tongtong Zhu, Dong Zou, Mengyao Liu, Yifan Zhang, Lu Wang, Zhang Zhang, Feng Liu
Journal: Genomics Proteomics & Bioinformatics (2025)

Abstract Advancements in high-throughput omics technologies have facilitated a systematic exploration of crucial hematopoietic organs across diverse species. A thorough understanding of hematopoiesis in vivo and facilitation of generating functional hematopoietic stem and progenitor cells (HSPCs) in vitro necessitate a comprehensive hematopoietic cross-stage developmental landscape across species. To address this need, we developed HemAtlas, a platform designed for the systematic mapping of hematopoiesis both in vivo and in vitro. HemAtlas features detailed analyses of multi-omics datasets from humans, mice, zebrafish, and HSPC in vitro culture systems. Utilizing literature curation and data normalization, HemAtlas integrates various functional modules, allowing interactive exploration and visualization of any collected omics data based on user-specific interests. Moreover, by applying a systematic and uniform integration method, we constructed organ-wide hematopoietic references for each species with manually curated cell annotations, enabling a comprehensive decoding of cross-stage developmental hematopoiesis at the organ level. Of particular significance are three distinctive functions–single-cell cross-stage, cross-species, and cross-model analysis–that HemAtlas employs to elucidate the hematopoietic development in zebrafish, mice, and humans, and to offer guidance on the generation of HSPCs in vitro. Simultaneously, HemAtlas incorporates a comprehensive map of HSPC cross-stage development to reveal HSPC stage-specific properties. Taken together, HemAtlas serves as a crucial resource to advance our understanding of hematopoiesis and is available at https://ngdc.cncb.ac.cn/hematlas/.
Population perspectives on benefits and harms of screening for metabolic dysfunction-associated steatotic liver disease
Authors: Alina M. Allen, W. Ray Kim, Patrizia Carrieri, Rachel Canning, Fang-Shu Ou, Joanne Benson, Jessica L. Olson, Sudhakar K. Venkatesh, Jiahui Li, Meng Yin, Maysa Eslami, Richard L. Ehman, Jennifer Hunter Berg, Jeffrey V. Lazarus
Journal: Hepatology (2025)

Screening for diseases can have psychological impacts, such as anxiety, and requires acceptability from the population to be effective. This study examined the perspectives on the benefits and harms of screening for metabolic dysfunction-associated steatotic liver disease (MASLD) among the general population to optimize screening practices. A survey was sent to participants enrolled between 2020-2024 in a prospective MASLD screening study in Olmsted County, MN. The survey assessed participants' perceived anxiety, stigma, quality of life, preferred screening methods, financial concerns, and lifestyle impacts following screening and diagnosis. Of the 461 participants, 342 (74%) completed the survey. Overall, 14% of participants reported screening-related anxiety and 14% were concerned about disclosing a potential MASLD diagnosis to others. Among those without a MASLD diagnosis, 99% felt reassured about their liver health, 48% reported an improved quality of life, and 25% made lifestyle changes pertaining to their diet, alcohol use, and physical activity. Of the 77 participants diagnosed with MASLD, 52% experienced some anxiety about their new diagnosis; however, 95% and 97% considered it important to receive an early MASLD diagnosis to mitigate the risk for cirrhosis and cardiovascular disease, respectively. Notably, 79% of diagnosed participants found the diagnosis beneficial in adopting healthier habits, with 30% achieving a >10% weight loss after screening. Conclusion: This population-based survey demonstrates that the perceived benefits of proactive MASLD screening, such as increased awareness, lifestyle changes, and early diagnosis, outweigh the harms. These findings highlight the importance of early screening through patient-centered protocols to improve health outcomes.
CAD-Driven pathways in hepatocellular carcinoma metastasis
Authors: Carmen Chak-Lui Wong, Chun-Ming Wong
Journal: Hepatology (2025)

1State Key Laboratory of Liver Research, the University of Hong Kong 2Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong 3Centre for Oncology and Immunology, Hong Kong Science Park, Hong Kong SAR, China Correspondence Carmen Chak-Lui Wong, Department of Pathology, T8-010, Block T, Queen Mary Hospital, 102 Pokfulam Road, Pokfulam, Hong Kong. Email: [email protected], [email protected] Chun-Ming Wong, State Key Laboratory, Rm 711, No. 5 Sassoon Road, Pokfulam, Hong Kong. Email: [email protected], [email protected]
Effect of albumin treatment duration on response rates and outcomes in patients with cirrhosis and acute kidney injury
Authors: Eva Maria Schleicher, Henrik Karbannek, Julia Weinmann-Menke, Peter Robert Galle, Andreas Stallmach, Simon Johannes Gairing, Alexander Zipprich, Cristina Ripoll, Christian Labenz
Journal: Journal of Hepatology (2025)

Guidelines recommended volume expansion with albumin for 48 hours for patients with cirrhosis and acute kidney injury (AKI) to correct hypovolemia and rule out prerenal AKI. A recent update in the Acute Disease Quality Initiative (ADQI)-International Club of Ascites (ICA) consensus guidelines suggested shortening this duration to 24 hours, primarily based on expert opinion. This study aimed to evaluate the response rates to albumin treatment after 24 and 48 hours and to compare and assess the prognostic significance of three different definitions of response to albumin therapy. Data from 127 prospectively recruited patients with cirrhosis and AKI from two German centers were analyzed. We examined three response definitions after 24 and 48 hours: (1) serum creatinine (SCr) decrease > 0.3 mg/dl, (2) SCr decrease >25 %, and (3) SCr decrease in at least one AKI stage. Follow-up was prolonged until liver transplantation, death or hemodialysis (HD). Overall, 30-54 % of the patients responded to albumin treatment depending on the definition, and response rates were balanced across AKI stages. Notably, a relevant number of patients who responded at 48 hours did not respond within the first 24 hours. Additional response to albumin during the second 24 hours were 38 %, 24 %, and 25 % (definitions 1, 2, and 3, respectively). Response according to definition 3 was associated with a better HD- and transplantation-free survival. A substantial proportion of patients requires 48 hours to respond to albumin treatment. Shortening time of albumin therapy may lead to overtreatment with terlipressin. This study provides valuable insights into the optimal duration of albumin treatment for patients with cirrhosis and acute kidney injury (AKI), challenging the recent recommendation of shortening the treatment period with albumin. Furthermore, the optimal definition for response to albumin (reduction of at least one AKI stage) has been assessed. The results of this study are highly clinically relevant since shortening albumin therapy may lead to overtreatment with terlipressin, and evidence to support the choice of the definition of response to albumin was lacking. Clinicians can use these findings to predict treatment outcomes better, avoid fluid overload, and improve patient prognosis while also considering the potential risks of early intervention with terlipressin.
Robust micelles formulation to improve systemic corticosteroid therapy in sepsis in multiple healthcare systems
Authors: Younes Louaguenouni, Qinglin Wang, Thomas Baticle, Catherine Cailleau, Elodie Lamy, Julie Mougin, David Chapron, Stanislas Grassin-Delyle, Juliette Vergnaud, Nicolas Tsapis, Elias Fattal, François Fay
Journal: Journal of Controlled Release (2025)
Sequential transitions of male sexual behaviors driven by dual acetylcholine-dopamine dynamics
Authors: Ai Miyasaka, Takeshi Kanda, Naoki Nonaka, Yuka Terakoshi, Yoan Cherasse, Yukiko Ishikawa, Yulong Li, Hotaka Takizawa, Arisa Hirano, Jun Seita, Masashi Yanagisawa, Takeshi Sakurai, Katsuyasu Sakurai, Qinghua Liu
Journal: Neuron (2025)

The neural mechanisms underlying the sequential transitions of male sexual behaviors, including mounting, intromission, and ejaculation, remain largely unexplored. Here, we report that acetylcholine (ACh)-dopamine (DA) dynamics in the ventral shell of the nucleus accumbens (vsNAc) regulate these sexual transitions in male mice. During intromission, the vsNAc displays a unique pattern of dual ACh-DA rhythms, generated by reciprocal regulation between ACh and DA signaling via nicotinic ACh receptors (nAChRs) and DA D2 receptors (D2Rs). Knockdown of choline acetyltransferase (ChAT) or D2R in the vsNAc diminishes the occurrence of intromission and ejaculation. Optogenetic manipulations demonstrated that DA signaling maintains sexual behaviors by suppressing D2RvsNAc neurons. Moreover, ACh signaling promotes the initiation of mounting and intromission and facilitates the intromission-ejaculation transition by inducing a slowdown in DA rhythm. Together, these findings reveal that coordinated ACh-DA dynamics in the vsNAc play a critical role in orchestrating the sequential transitions of male sexual behaviors.
A polygenic score for height identifies an unmeasured genetic predisposition among pediatric patients with idiopathic short stature
Authors: John P. Shelley, Mingjian Shi, Josh F. Peterson, Sara L. Van Driest, Jill H. Simmons, Jonathan D. Mosley
Journal: Genome Medicine (2025)

Abstract Background A subset of children with short stature do not have an identified clinical explanation after extensive diagnostic evaluation. We hypothesized that a polygenic score for height (PGS height ) could identify children with non-familial idiopathic short stature (ISS-NF) who carry a polygenic predisposition to shorter height that is not accounted for by existing measures. Methods We studied 534 pediatric participants in an electronic health record (EHR)-linked DNA biobank (BioVU) who had been evaluated for short stature by an endocrinologist. Participants were classified as having one of five short stature subtypes: primary growth disorders, secondary growth disorders, idiopathic short stature (ISS), which was sub-classified into familial (ISS-F) and non-familial (ISS-NF), and constitutional delay of puberty (ISS-DP). Differences in polygenic predisposition between subtypes were analyzed using a validated PGS height which was standardized to a standard deviation score (SDS). Adult height predictions were generated using the PGS height and mid-parental height (MPH). Within-child differences in height predictions were compared across subtypes. Logistic regression models and AUC analyses were used to test the ability of the PGS height to differentiate ISS-NF from growth disorders. The incremental improvement (ΔAUC) of adding the PGS height to prediction models with MPH was also estimated. Results Among the 534 participants, 29.0% had secondary growth disorders, 24.9% had ISS-F, 20.2% had ISS-NF, 17.2% had ISS-DP, and 8.6% had primary growth disorders. Participants with ISS-NF had similar PGS height values to those with ISS-F (difference [Δ] in PGS height SDS [95% CI] = 0.19 [− 0.31 to 0.70], p = 0.75). Predicted heights generated by the PGS height were lower than the MPH estimate for children with ISS-NF (Δ[PGS height − MPH] = − 0.37 SDS; p = 3.2 × 10 −9 ) but not for children with ISS-F (Δ = − 0.07; p = 0.56). Children with ISS-NF also had lower PGS height than children with primary growth disorders (ΔPGS height = − 0.53 [− 1.03 to − 0.04], p = 0.03) and secondary growth disorders (Δ = − 0.45 [− 0.80 to − 0.10], p = 0.005). The PGS height improved model discrimination between ISS-NF and children with primary (ΔAUC, + 0.07 [95% CI, 0.02 to 0.17]) and secondary growth disorders (ΔAUC, + 0.03 [95% CI, 0.01 to 0.10]). Conclusions Some children with ISS-NF have an unrecognized polygenic predisposition to shorter height, similar to children with ISS-F and greater than those with growth disorders. A PGS height could aid clinicians in identifying children with a benign, polygenic predisposition to shorter height.