tbuckley/cabot-search huggingface dataset:
Dual modality feature fused neural network integrating binding site information for drug target affinity prediction
Authors: Haohuai He, Guanxing Chen, Zhenchao Tang, Calvin Yu-Chian Chen
Journal: npj Digital Medicine (2025)

Abstract Accurately predicting binding affinities between drugs and targets is crucial for drug discovery but remains challenging due to the complexity of modeling interactions between small drug and large targets. This study proposes DMFF-DTA, a dual-modality neural network model integrates sequence and graph structure information from drugs and proteins for drug-target affinity prediction. The model introduces a binding site-focused graph construction approach to extract binding information, enabling more balanced and efficient modeling of drug-target interactions. Comprehensive experiments demonstrate DMFF-DTA outperforms state-of-the-art methods with significant improvements. The model exhibits excellent generalization capabilities on completely unseen drugs and targets, achieving an improvement of over 8% compared to existing methods. Model interpretability analysis validates the biological relevance of the model. A case study in pancreatic cancer drug repurposing demonstrates its practical utility. This work provides an interpretable, robust approach to integrate multi-view drug and protein features for advancing computational drug discovery.
To close or not to close after colorectal endoscopic submucosal dissection: that is the question!
Authors: Jeremie Jacques
Journal: Endoscopy (2025)

En bloc resection by endoscopic submucosal dissection (ESD) is increasingly adopted worldwide as the first-line treatment for large (≥20 mm) superficial colorectal neoplasia. Its advantages include complete pathological analysis, the potential to cure selected T1 colorectal cancers, and single-session R0 resection that can obviate the need for early follow-up colonoscopies.
Surveillance of primary sclerosing cholangitis – a comparison of scheduled or on-demand ERCP with annual MRI surveillance: a multicenter study
Authors: Nina Barner-Rasmussen, Antonio Molinaro, Bregje Mol, Cyriel Ponsioen, Annika Bergquist, Hannu Kautiainen, Martti A. Färkkilä
Journal: Endoscopy (2025)

Abstract Primary sclerosing cholangitis (PSC) is associated with a high risk of hepatobiliary malignancy, especially cholangiocarcinoma (CCA). There are no good tumor markers to screen for CCA, and current recommendations for PSC monitoring are mainly based on expert opinions. The optimal strategy to assess disease progression and screen for CCA – the main cause of death of PSC patients – remains unclear. We aimed to compare three different surveillance strategies and their effect on patient outcomes. Data from three distinct PSC cohorts with different surveillance strategies – scheduled endoscopic retrograde cholangiopancreatography (ERCP), annual magnetic resonance imaging/cholangiopancreatography (MRI/MRCP) surveillance, and on-demand ERCP according to ESGE/EASL guidelines – was collected. Patients with PSC diagnosed in 1990 or later were included and the last day of follow-up was 31 December 2023. The composite end point consisted of hepatobiliary malignancy, liver transplantation, or liver-related death. 1629 PSC patients were included, with a median follow-up of 8–11 years. The cumulative incidence of the composite end point was lowest in the group undergoing scheduled ERCP (14.1%, 95%CI 12.0%–16.4%) and highest in the on-demand ERCP cohort (35.0%, 95%CI 28.4%–42.0%). Although the cumulative incidence of CCA was lower in the scheduled ERCP group than in the other groups, it did not differ statistically significantly from the MRI/MRCP surveillance group. No differences were seen in liver-related deaths between the surveillance strategies. In this study comparing scheduled ERCP, annual MRI/MRCP surveillance, and on-demand ERCP, the strategy based on scheduled ERCP using individual risk stratification is associated with better overall prognosis and outcome.
A phenotype-based AI pipeline outperforms human experts in differentially diagnosing rare diseases using EHRs
Authors: Xiaohao Mao, Yu Huang, Ye Jin, Lun Wang, Xuanzhong Chen, Honghong Liu, Xinglin Yang, Haopeng Xu, Xiaodong Luan, Ying Xiao, Siqin Feng, Jiahao Zhu, Xuegong Zhang, Rui Jiang, Shuyang Zhang, Ting Chen
Journal: npj Digital Medicine (2025)

Abstract Rare diseases, affecting ~350 million people worldwide, pose significant challenges in clinical diagnosis due to the lack of experienced physicians and the complexity of differentiating between numerous rare diseases. To address these challenges, we introduce PhenoBrain, a fully automated artificial intelligence pipeline. PhenoBrain utilizes a BERT-based natural language processing model to extract phenotypes from clinical texts in EHRs and employs five new diagnostic models for differential diagnoses of rare diseases. The AI system was developed and evaluated on diverse, multi-country rare disease datasets, comprising 2271 cases with 431 rare diseases. In 1936 test cases, PhenoBrain achieved an average predicted top-3 recall of 0.513 and a top-10 recall of 0.654, surpassing 13 leading prediction methods. In a human-computer study with 75 cases, PhenoBrain exhibited exceptional performance with a top-3 recall of 0.613 and a top-10 recall of 0.813, surpassing the performance of 50 specialist physicians and large language models like ChatGPT and GPT-4. Combining PhenoBrain’s predictions with specialists increased the top-3 recall to 0.768, demonstrating its potential to enhance diagnostic accuracy in clinical workflows.
Centrosome protein TAX1BP mediates STING-dependent immune response and potentiates anti-PD-1 efficacy in Hepatocellular Carcinoma
Authors: Qingmei Zhang, Wing-Lim Chan, Sin-Yee Fung, Li Pang, Tao Ding, Jia Ming Nickolas Teo, Yuan Zhou, Chung Ming Alex Wu, Kam-Leung Siu, Jiacheng Bi, Guang Sheng Ling, Dong-Yan Jin, Kwan Man, Yick Pang Ching
Journal: Molecular Therapy (2025)
Outcomes After Surgical Management of Early-Stage Lung Cancer in Octogenarians: An in-depth Analysis of a Nationally Representative Cohort
Authors: Ian C Bostock, Adam H Fox, Ralph C Ward, Kathryn E Engelhardt, Farhood Farjah, Chi-Fu Jeffrey Yang, Robert A Smith, Barry C Gibney, Gerard A Silvestri
Journal: Journal of Thoracic Oncology (2025)
Endothelial Colony-Forming Cells (ECFCs) in Cerebrovascular Aging: Focus on the Pathogenesis of Vascular Cognitive Impairment and Dementia (VCID), and Treatment Prospects
Authors: Sharon Negri, Zeke Reyff, Eva Troyano-Rodriguez, Madison Milan, Jennifer Ihuoma, Sherwin Tavakol, Helen Shi, Roland Patai, Raymond Jiang, Jonah Mohon, Jed Boma-Iyaye, Zoltan Ungvari, Anna Csiszar, Andriy Yabluchanskiy, Francesco Moccia, Stefano Tarantini
Journal: Ageing Research Reviews (2025)
Long-chain acylcarnitine deficiency promotes hepatocarcinogenesis
Authors: Kaifeng Wang, Zhixian Lan, Heqi Zhou, Rong Fan, Huiyi Chen, Hongyan Liang, Qiuhong You, Xieer Liang, Ge Zeng, Rui Deng, Yu Lan, Sheng Shen, Peng Chen, Jinlin Hou, Pengcheng Bu, Jian Sun
Journal: Acta Pharmaceutica Sinica B (2025)

Despite therapy with potent antiviral agents, chronic hepatitis B (CHB) patients remain at high risk of hepatocellular carcinoma (HCC). While metabolites have been rediscovered as active drivers of biological processes including carcinogenesis, the specific metabolites modulating HCC risk in CHB patients are largely unknown. Here, we demonstrate that baseline plasma from CHB patients who later developed HCC during follow-up exhibits growth-promoting properties in a case-control design nested within a large-scale, prospective cohort. Metabolomics analysis reveals a reduction in long-chain acylcarnitines (LCACs) in the baseline plasma of patients with HCC development. LCACs preferentially inhibit the proliferation of HCC cells in vitro at a physiological concentration and prevent the occurrence of HCC in vivo without hepatorenal toxicity. Uptake and metabolism of circulating LCACs increase the intracellular level of acetyl coenzyme A, which upregulates histone H3 Lys14 acetylation at the promoter region of KLF6 gene and thereby activates KLF6/p21 pathway. Indeed, blocking LCAC metabolism attenuates the difference in KLF6/p21 expression induced by baseline plasma of HCC/non-HCC patients. The deficiency of circulating LCACs represents a driver of HCC in CHB patients with viral control. These insights provide a promising direction for developing therapeutic strategies to reduce HCC risk further in the antiviral era.
Predictors of perceived stress, perceived stigmatization and body dysmorphia in patients with chronic prurigo/prurigo nodularis: results from an observational cross-sectional multicentre European Study in 17 countries
Authors: A S Ficheux, E Brenaut, C Schut, F J Dalgard, A Bewley, Henriet van Middendorp, U Gieler, L Lien, F Sampogna, S Ständer, L Tomas-Aragones, N Vulink, A Y Finlay, F J Legat, G Titeca, G B Jemec, C Szabó, V Grivcheva Panovska, S Spillekom van Koulil, F Balieva, J C Szepietowski, A Reich, B R Ferreira, A Lvov, D Romanov, S E Marron, T Gracia Cazaña, Å Svensson, I K Altunay, A R Thompson, C Zeidler, J Kupfer, L Misery
Journal: Journal of the American Academy of Dermatology (2025)
Solvent volatilization annealing-prepared Janus film with asymmetric bioadhesion and inherent biological functions to expedite oral ulcer healing
Authors: Yanlv Chen, Wanru Meng, Hailing Yu, Chuandong He, Meng Yu, Yitong Zhou, Yuhan Jiang, Liming Bian, Xin Peng
Journal: Biomaterials (2025)
Endoscopic ultrasound-guided drainage of bilomas in difficult-to-puncture locations using a sheath-assisted puncture technique
Authors: Kazuki Hama, Yukitoshi Matsunami, Takayoshi Tsuchiya, Reina Tanaka, Ryosuke Tonozuka, Shuntaro Mukai, Takao Itoi
Journal: Endoscopy (2025)

Biloma is a complication of transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) [1]. Despite being the first-line treatment for infected bilomas, percutaneous drainage can affect daily life and pose self-extraction risks, particularly in older patients [2]. Endoscopic ultrasound (EUS)-guided drainage offers a viable alternative for internal biliary drainage; however, it can be challenging for the right liver lobe because of its long distance from the gastrointestinal (GI) tract [3] [4] [5]. Here, we describe successful EUS-guided drainage of an infected biloma distant from the GI tract using a sheath-assisted puncture technique ([Fig. 1], [Video 1]).
‘I wish I had been better prepared’: a mixed-methods study of psychological reactions, perceptions and opinions of cardiovascular preparticipation screening among young competitive athletes
Authors: Nicholas Grubic, Matthew Fraser, Meghan K Ford, Braeden Hill, Laura E Mantella, Valentina Mihajlovic, Ryan Bennett, Rohaan Syan, Anhadh Law, Jane S Thornton, Amer M Johri
Journal: British Journal of Sports Medicine (2025)

Objective To evaluate the psychological reactions, perceptions and opinions of cardiovascular preparticipation screening (PPS) among young competitive athletes. Methods This convergent parallel mixed-methods study recruited 222 athletes (mean age: 18.7 years) who underwent PPS at a Canadian university. All athletes completed a cardiovascular history questionnaire, and a subgroup (n=165) additionally obtained an ECG and physical exam. On registering for PPS, athletes completed a psychological impact survey. Survey items were measured on a 5-point scale, ranging from −2 (strongly disagree) to 2 (strongly agree) and reported as means. After completing PPS, 18 athletes participated in focus groups or interviews to explore screening experiences. Qualitative data were analysed using reflexive thematic analysis, following an inductive and critical realist approach. Results Athletes reported minimal symptoms of anxiety (−1.29), stress (−1.41) or worry (−1.12) concerning their participation in PPS and agreed that screening was beneficial for their safety (1.25). Psychological symptoms were higher in athletes who reported cardiovascular symptoms or a family history than those who did not. Athletes required to undergo an ECG and physical exam were less anxious, stressed and worried about PPS but more interested in learning about their results than those screened with only a history questionnaire. Three themes described athletes’ responses to PPS: (1) importance of communication and service navigation; (2) distress surrounding the uncertainty of results and (3) screening as a non-disruptive and essential part of ‘being an athlete’. Conclusion The PPS process does not lead to excessive distress among young competitive athletes before, during or after screening. Athletes identified solutions to enhance the PPS experience, including tailored educational resources and an integrated support system to manage psychological symptoms.
The association between Guardian Cap use during practices and sport-related concussion risk in high school American football players
Authors: Erin Hammer, Sam Mosiman, Mikel R Joachim, Ethan Taylor, Adam Cordum, M Alison Brooks, Timothy McGuine
Journal: British Journal of Sports Medicine (2025)

Objective Guardian Caps (GCs) have been widely implemented at all levels of American football participation based on laboratory evidence that they may reduce head impact forces. The purpose of this study was to determine if GC use during practice was associated with a lower risk of sport-related concussion (SRC) during practices and games among high school football players. Methods Data were collected on 2610 athletes from 41 Wisconsin schools that self-selected into GC or Non-GC cohorts. Athletic trainers recorded practice and game exposures and SRCs through the 2023 season. Generalised linear mixed models were built to determine the effect of GC utilisation on SRC rates, accounting for school and player exposures. Results In the total cohort (Non-GC n=1188 (45.5%); GC n=1422 (54.5%)), 180 athletes (6.9%) sustained SRCs. 64 SRCs occurred during practice (GC n=33 (51.6%); Non-GC n=31 (48.4%)). GC use was not associated with a decreased risk of SRC during practice in the univariable analysis (relative risk (RR)=1.04, 95% CI 0.58 to 1.86, p=0.90) or after accounting for previous SRC within the last year (RR 1.01, 95% CI 0.57 to 1.79, p=0.97). No players of either cohort wore GCs during games. There were 116 SRCs sustained during games (GC n=68 (58.6%); Non-GC n=48 (41.4%)). GC use during practice was not associated with the risk of SRC during games in the univariable analysis (RR 1.13, 95% CI 0.72 to 1.78, p=0.60) or after accounting for previous SRC within the last year (RR 1.13, 95% CI 0.71 to 1.78, p=0.61). Conclusion GC use during practice in high school American football players was not associated with a decreased risk of sustaining SRC in practice or games.
Designer Organs: Ethical Genetic Modifications in the Era of Machine Perfusion
Authors: Irina Filz von Reiterdank, Raphaela Bento, Insoo Hyun, Rosario Isasi, Susan M. Wolf, J. Henk Coert, Aebele B. Mink van der Molen, Biju Parekkadan, Korkut Uygun
Journal: Annual Review of Biomedical Engineering (2025)

Gene therapy is a rapidly developing field, finally yielding clinical benefits. Genetic engineering of organs for transplantation may soon be an option, thanks to convergence with another breakthrough technology, ex vivo machine perfusion (EVMP). EVMP allows access to the functioning organ for genetic manipulation prior to transplant. EVMP has the potential to enhance genetic engineering efficiency, improve graft survival, and reduce posttransplant complications. This will enable genetic modifications with a vast variety of applications, while raising questions on the ethics and regulation of this emerging technology. This review provides an in-depth discussion of current methodologies for delivering genetic vectors to transplantable organs, particularly focusing on the enabling role of EVMP. Organ-by-organ analysis and key characteristics of various vector and treatment options are assessed. We offer a road map for research and clinical translation, arguing that achieving scientific benchmarks while creating anticipatory governance is necessary to secure societal benefit from this technology.
Cell-Instructive Biomaterials with Native-Like Biochemical Complexity
Authors: Tuba Marjan, Nuria Lafuente-Gómez, Akaansha Rampal, David J. Mooney, Shelly R. Peyton, Taimoor H. Qazi
Journal: Annual Review of Biomedical Engineering (2025)

Biochemical signals in native tissue microenvironments instruct cell behavior during many biological processes ranging from developmental morphogenesis and tissue regeneration to tumor metastasis and disease progression. The detection and characterization of these signals using spatial and highly resolved quantitative methods have revealed their existence as matricellular proteins in the matrisome, some of which are bound to the extracellular matrix while others are freely diffusing. Including these biochemical signals in engineered biomaterials can impart enhanced functionality and native-like complexity, ultimately benefiting efforts to understand, model, and treat various diseases. In this review, we discuss advances in characterizing, mimicking, and harnessing biochemical signals in developing advanced engineered biomaterials. An overview of the diverse forms in which these biochemical signals exist and their effects on intracellular signal transduction is also provided. Finally, we highlight the application of biochemically complex biomaterials in the three broadly defined areas of tissue regeneration, immunoengineering, and organoid morphogenesis.
Single-Session Interventions for Mental Health Problems and Service Engagement: Umbrella Review of Systematic Reviews and Meta-Analyses
Authors: Jessica L. Schleider, Juan Pablo Zapata, Andy Rapoport, Annie Wescott, Arka Ghosh, Benji Kaveladze, Erica Szkody, Isaac L. Ahuvia
Journal: Annual Review of Clinical Psychology (2025)

Most people with mental health needs cannot access treatment; among those who do, many access services only once. Accordingly, single-session interventions (SSIs) may help bridge the treatment gap. We conducted the first umbrella review synthesizing research on SSIs for mental health problems and service engagement in youth and adults. Our search yielded 24 systematic reviews of SSIs, which included 415 unique trials. Twenty reviews (83.33%) reported significant, positive effects of SSIs for one or more outcomes (anxiety, depression, externalizing problems, eating problems, substance use, treatment engagement or uptake). Across 12 reviews that meta-analytically examined SSIs’ effectiveness relative to controls, SSIs showed a positive effect across outcomes and age groups (standardized mean difference = −0.25, I 2 = 43.17%). Per AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews), some methodological concerns emerged across reviews, such as low rates of preregistration. Overall, findings support the clinical utility of SSIs for certain psychological problems and populations. Implementation research is needed to integrate effective SSIs into systems of care.
Emerging Technologies for Multiphoton Writing and Reading of Polymeric Architectures for Biomedical Applications
Authors: Jieliyue Sun, Sixian Jia, Chenhui Shao, Michelle R. Dawson, Kimani C. Toussaint
Journal: Annual Review of Biomedical Engineering (2025)

The rise in popularity of two-photon polymerization (TPP) as an additive manufacturing technique has impacted many areas of science and engineering, particularly those related to biomedical applications. Compared with other fabrication methods used for biomedical applications, TPP offers 3D, nanometer-scale fabrication dexterity (free-form). Moreover, the existence of turnkey commercial systems has increased accessibility. In this review, we discuss the diversity of biomedical applications that have benefited from the unique features of TPP. We also present the state of the art in approaches for patterning/writing and reading 3D TPP-fabricated structures. The reading process influences the fidelity for both in situ and ex situ characterization methods. We also review efforts to leverage machine learning to facilitate process control for TPP. Finally, we conclude with a discussion of both the current challenges and exciting opportunities for biomedical applications that lie ahead for this intriguing and emerging technology.
Integrin Trafficking, Fibronectin Architecture, and Glomerular Injury upon AdipoR1 Depletion
Authors: Sonja Lindfors, Constanze Schmotz, Dominik Lewandowski, Annika Hau, Leena Saikko, Eero Lehtonen, Ville Majaniemi, Minna Karhe, Jette-Britt Naams, Harry Nisen, Jukka Tienari, Moin A. Saleem, Katharina Pfeil, Heiko Bugger, Kirsi H. Pietiläinen, Tuomas Mirtti, Krzysztof Palczewski, Sanna Lehtonen
Journal: Journal of the American Society of Nephrology (2025)

Background: Deficiency of adiponectin and its downstream signaling may contribute to the pathogenesis of kidney injury in type 2 diabetes. Adiponectin activates intracellular signaling via adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2), but the role of AdipoR-mediated signaling in glomerular injury in type 2 diabetes remains unknown. Methods: The expression of AdipoR1 in the kidneys of people with type 2 diabetes and the expression of podocyte proteins or injury markers in the kidneys of AdipoR1-knockout (AdipoR1-KO) mice and immortalized AdipoR1-deficient human podocytes were investigated by immunohistochemistry and immunoblotting. The functional role of AdipoR1 was studied in AdipoR1-deficient podocytes by performing assays for apoptosis, cytokine secretion, mechanical stress, adhesion, and endocytic trafficking. Results: Glomerular AdipoR1 expression was lower in type 2 diabetes and associated kidney disease, correlating with higher BMI and podocyte loss. Male AdipoR1-KO mice showed typical signs of early diabetic kidney disease, including albuminuria, glomerular structural abnormalities, and lower expression of central podocyte proteins; females were less affected. Podocyte apoptosis increased in female and male AdipoR1-KO mice and excessive podocyte loss, potentially due to detachment, was detected in males. AdipoR1 deficiency impaired the YAP-mediated mechanoresponse and induced accumulation of the extracellular matrix (ECM) protein fibronectin in the glomeruli in vivo , and podocytes in vitro . Functionally, AdipoR1 deficiency impaired endocytosis of the ECM receptor active integrin β1, disturbed focal adhesion turnover, and remodulated podocyte-derived ECM, thereby reducing podocyte adhesion. Conclusions: AdipoR1 deficiency in mice resulted in the development of kidney injury predominantly in males. Mechanistically, AdipoR1 loss in podocytes impaired endocytosis of active integrin β1, which plausibly compromised focal adhesion dynamics, disturbed fibronectin matrix turnover, and hindered podocyte adhesion.