tbuckley/cabot-search huggingface dataset:
Beneficial infections of the enterovirus genus in patients with liver cancer
Authors: Lichun Ma, Man Hsin Hung, Farid Rashidi Mehrabadi, Limin Wang, Qin Li, Marshonna Forgues, Kathy Cheng Wang, Anuradha Budhu, Julián Candia, Jittiporn Chaisaingmongkol, Siritida Rabibhadana, Benjarath Pupacdi, Mathuros Ruchirawat, Xin Wei Wang
Journal: Gut (2025)

Background Hepatocellular carcinoma (HCC) is a significant global cancer burden, with rising incidence and lacking a unified prevention strategy due to complex aetiologies. Viral exposures may shape host immunity via specific reactive viral antigens that could induce immune responses against hepatocarcinogenesis. Objective We aimed to characterise viral exposure differences between HCC patients and healthy individuals and identify potentially protective viral antigens against HCC. Design We profiled pan-viral serological antibody repertoires using a microbial phage library among 2647 study subjects and examined the biological activities of selective viral antigens on blood-derived immune cells from both healthy individuals and HCC patients. Result We identified 153 viral antigens with a significantly reduced serological response in HCC patients compared with healthy individuals. We also observed that a higher serological response to 153 viral antigens is associated with better clinical outcomes of patients with chronic liver diseases and HCC. These findings are consistent across different populations across sex, ethnicity and aetiology. We identified a common epitope (CE1) shared among 39% of reactive viral antigens that belong to the rhinovirus and enterovirus families. We demonstrated that CE1 could induce both CD4 + and CD8 + T-cell activation and CD8 + T-cell-mediated HCC cell killing. Conclusions Our results suggest that past exposures to members of the Enterovirus genus may be advantageous for cancer patients, highlighting the potential for a viral peptide-based HCC vaccine.
Therapeutic Unmet Needs in Brachioradial Pruritus
Authors: Giulia Coscarella, Yael Rosen, Nathanael Singer, Eli Eyal, Linor Haimson, Orna Goren, Esther Hagai, Manuel Pereira, Sonja Stander, Gil Yosipovitch
Journal: British Journal of Dermatology (2025)

Brachioradial pruritus (BRP) is a chronic, underdiagnosed neuropathic itch, with a majority of patients experiencing significant diagnostic delays, inadequate symptom relief, and limited access to mechanism-targeted therapies. Our global patient survey reveals critical gaps in awareness, diagnosis and treatment, highlighting the urgent need for interdisciplinary management strategies and standardized care pathways.
A Deep Learning Model for Classifying Left Ventricular Enlargement for both Transthoracic Echocardiograms and Handheld Cardiac Ultrasound
Authors: Jeffrey G Malins, D M Anisuzzaman, John I Jackson, Eunjung Lee, Jwan A Naser, Jared G Bird, Paul A Friedman, Christie C Ngo, Jae K Oh, Gal Tsaban, Patricia A Pellikka, Jeremy J Thaden, Francisco Lopez-Jimenez, Zachi I Attia, Sorin V Pislaru, Garvan C Kane
Journal:  (2025)

Abstract Aims To develop a deep learning model that: (1) utilizes transthoracic echocardiography (TTE) clips to detect LV enlargement without being provided information regarding a patient’s sex and body size; and (2) can be accurately applied to clips acquired using either standard comprehensive TTE or handheld cardiac ultrasound (HCU). Methods and Results Using retrospective TTE data (training: 8,722 patients; internal validation: 468 patients), we developed a deep learning model that estimates a patient’s end-diastolic LV volume (indexed to body surface area and normalized across the sexes), and then thresholds this estimate to perform the following classifications: (1) normally-sized LV vs. ≥ mild LV enlargement; (2) normal/mildly enlarged LV vs. ≥ moderate LV enlargement. For retrospective datasets, the model showed strong performance in TTE across three geographically distinct locations (Minnesota and Wisconsin: 1,082 patients, AUC = 0.925 and 0.953 for classifications 1 and 2, respectively; Arizona: 1,475 patients, AUC = 0.935 and 0.969; and Florida: 1,481 patients, AUC = 0.934 and 0.970). Additionally, performance was strong for both TTE and HCU clips collected from a prospective cohort of 410 patients who underwent HCU immediately following TTE (TTE: AUC = 0.925 and 0.971; HCU: AUC = 0.874 and 0.902, for classifications 1 and 2, respectively.). Conclusion An automated deep learning model applied to TTE or HCU images accurately categorizes LV volumes. These results lay a foundation for future work aimed at optimizing clinical outcomes for heart failure patients by enabling early detection of LV enlargement across various point-of-care settings.
Targeting the MAPK Pathway for NRAS Mutant Melanoma: From Mechanism to Clinic
Authors: Yi Wang, Guangchao Xu, Hongwei Xia
Journal: British Journal of Dermatology (2025)

Abstract Mutant NRAS is the second-most common type of mutation in melanoma. The prognosis is poor in the patients with NRAS mutant melanoma, and effective targeted treatment strategies are still lacking. Mutant NRAS mainly acts through activating the RAF-MEK-ERK signaling to promote the carcinogenesis in melanoma. In recent years, significant clinical advancements have been achieved by targeting the NRAS-MAPK pathway, with novel therapies such as the MEK inhibitor tunlametinib and the combination therapy of the pan-RAF inhibitor naporafenib with trametinib leading the way. In this review, we will systematically summarize the recent advances in the direct targeting of mutant NRAS proteins and their downstream RAF and MEK proteins, as well as targeting the MAPK pathway in combination with other therapeutic targets, including the immunotherapy, to treat NRAS mutant melanoma. Additionally, we will further discuss the current issues and emerging countermeasures related to targeted therapy for NRAS mutant melanoma.
SAT-239 Comparative study on the efficacy of TIPS versus Non-TIPS treatments for hepatic portal vein thrombosis complicated by upper gastrointestinal hemorrhage
Authors: Rongjiong Zheng, Tongtong Shao, Jingli Zhang, Li Yang, Xinting Li, Ziyi Zhang, Keying Xu, Xiaobo Lu
Journal: Journal of Hepatology (2025)
SAT-467 Fibroblast activation assessed by PRO-C3 and PRO-C6 is associated to accumulation of key bile acids - A hallmark of fibrosis initiation and mortality in alcohol-related liver disease
Authors: Andressa de Zawadzki, Maja Thiele, Stine Johansen, Peter Andersen, Ida Falk Villesen, Tommi Suvitaival, Morten Karsdal, Cristina Legido-Quigly, Diana Julie Leeming, Aleksander Krag
Journal: Journal of Hepatology (2025)
LBP-029-YI Spatial transcriptomics of the tumor microenvironment discriminates inflamed tumors responsive or resistant to atezolizumab + bevacizumab in patients with advanced HCC
Authors: Marta Piqué-Gili, Anna Vila-Escoda, Marta Casado-Pelaez, Roser Pinyol, Ana Hernandez de Sande, Verónica Davalos, Albert Gris-Oliver, Carla Montironi, Judit Peix, Eduard Porta-Pardo, Daniela Grases, Sarah Cappuyns, Ezequiel Mauro, Guillem Cano-Segarra, Igor Figueiredo, Giorgio Ioannou, Edgar Gonzalez-Kozlova, Tim Meyer, Anja Lachenmayer, Jens U. Marquardt, Helen Reeves, Julien Edeline, Fabian Finkelmeier, Jörg Trojan, Jean-Frédéric Blanc, Richard Hubner, Matthias Pinter, Tom Luedde, Arndt Vogel, Sacha Gnjatic, Daniela Sia, Vincenzo Mazzaferro, Jeroen Dekervel, Manel Esteller, Josep M. Llovet
Journal: Journal of Hepatology (2025)
Long-term efficacy and safety of upadacitinib in patients with moderately to severely active ulcerative colitis: an interim analysis of the phase 3 U-ACTIVATE long-term extension study
Authors: Remo Panaccione, Séverine Vermeire, Silvio Danese, Peter D R Higgins, Gary R Lichtenstein, Hiroshi Nakase, Sarah Glover, Jean-Frédéric Colombel, Jason Eccleston, Michelle Kujawski, Valencia Remple, Xuan Yao, Ziqian Geng, Hannah Palac, Dolly Sharma, Smitha Suravaram, Stefan Schreiber
Journal: The Lancet. Gastroenterology & hepatology (2025)
Spousal Support and Physician Work-Life Integration and Burnout
Authors: Ciara C. O’Sullivan, Sarah Jenkins, Andrea N. Leep Hunderfund, Kathryn J. Ruddy, Colin P. West, Ariela L. Marshall
Journal: JAMA Network Open (2025)

Importance Few studies have assessed whether factors outside the workplace, such as support from a spouse or partner, are associated with work-life integration (WLI) satisfaction and burnout among physicians. Evaluating such an association may help with developing novel strategies to address burnout and improve WLI satisfaction among this group. Objectives To compare spousal support among female and male physicians and explore associations of spousal support with WLI satisfaction and burnout. Design, Setting, and Participants This cross-sectional, multispecialty survey study was conducted among 661 faculty physicians employed at an academic medical center from March 26 to May 22, 2024. Main Outcomes and Measures Survey items measured spousal support (5 items), WLI satisfaction (1 item), and burnout (2 Maslach Burnout Inventory items). Associations of spousal support and gender with WLI and burnout were assessed using logistic regression analyses adjusting for age, race and ethnicity, weekly work hours, and weekly hours spent on household or childcare duties. Results Overall, 739 of 2103 faculty physicians (response rate, 35.1%) completed the survey, of whom 661 (89.4%) were currently married or partnered (359 of 661 men [54.3%]). In this subset, 322 of 351 male physicians (91.7%) and 276 of 298 of female physicians (92.6%) reported frequent career support (defined as often, most of the time, or always) over the last year from their spouse or partner. Physicians reporting high levels of career support from their spouse or partner had higher odds of WLI satisfaction (odds ratio [OR], 1.50 [95% CI, 1.22-1.86]; P &amp;amp;lt; .001) and lower odds of burnout (OR, 0.73 [95% CI, 0.61-0.87]; P &amp;amp;lt; .001), independent of gender and adjusted for age, race and ethnicity, weekly work hours, and weekly hours spent on household or childcare duties. Male physicians had higher odds of WLI satisfaction than female physicians (OR, 1.95 [95% CI, 1.32-2.90]; P &amp;amp;lt; .001), even after adjusting for spousal career support and other covariates listed, whereas odds of burnout did not significantly differ by gender (OR, 0.84 [95% CI, 0.57-1.23]; P = .37). Conclusions and Relevance This study suggests that the level of career support from a spouse or partner is associated with WLI satisfaction and burnout among physicians, independent of gender. Future studies should explore whether interventions designed to enhance career support can improve WLI and well-being among physicians.
Short-term versus long-term mentalization-based therapy for borderline personality disorder (MBT-RCT): 24 months follow-up of a randomized clinical trial
Authors: Sophie Juul, Janus Christian Jakobsen, Emilie Hestbaek, Caroline Barkholt Kamp, Markus Harboe Olsen, Marie Rishede, Frederik Weischer Frandsen, Sune Bo, Stig Poulsen, Per Sørensen, Anthony Bateman, Sebastian Simonsen
Journal: Psychotherapy and Psychosomatics (2025)

Introduction Borderline personality disorder (BPD) is a severe and prevalent psychiatric disorder. Mentalization-based therapy (MBT) is an evidence-based intervention for BPD, which is often delivered as a long-term psychotherapy program for BPD. We previously published a randomized clinical trial assessing short-term versus long-term MBT for BPD 16 months after randomization as the primary follow-up time-point. Objectives To assess the long-term (24 months) results of short-term versus long-term MBT for outpatients with BPD. Methods Adult outpatients (≥18 years) with subthreshold or diagnosed BPD were randomly assigned (1:1) to short-term MBT (5 months) or long-term MBT (14 months). The primary outcome was BPD symptoms assessed with the Zanarini Rating Scale for Borderline Personality Disorder. Secondary outcomes were level of functioning (assessed using the Work and Social Adjustment Scale), quality of life (assessed using Short Form Health Survey, SF-36), global functioning (assessed using the Global Assessment of Functionins scale, GAF), and severe self-harm. All outcomes were assessed at 24 months after randomization. Results Between October 4, 2018, and December 3, 2020, we randomly assigned 166 participants to short-term MBT (n=84) or long-term MBT (n=82). After 24 months, regression analyses showed no evidence of a difference when assessing the primary outcome, BPD symptoms (ZAN-BPD MD -0.56; 95% CI -2.67 to 1.54; p = 0.598), level of functioning (WSAS MD -1.42% CI -5.04 to 2.21; p = 0.440), global functioning (GAF MD 2.51 95% CI: -1.65 to 6.67; p = 0.234), or severe self-harm (RR 1.38; 95% CI 0.88 to 2.21; p = 0.149). Regression analyses showed evidence of a beneficial effect of long-term MBT when assessing
A Case of Cryptic CBFB::MYH11 Acute Myeloid Leukemia With Noncanonical Breakpoints Detected by Optical Genome Mapping
Authors: Eduardo Edelman Saul, Samuel Urrutia, Hui Yang, Guillermo Montalban-Bravo, Guilin Tang, Gokce Toruner, Keyur Patel, Rajyalakshmi Luthra, Carlos Bueso-Ramos, Sa A. Wang, Kelly Chien, Koji Sasaki, Himachandana Atluri, Hannah Goulart, Beenu Thakral, Guillermo Garcia-Manero, Rashmi Kanagal-Shamanna
Journal: Journal of the National Comprehensive Cancer Network (2025)

Accurate and timely detection of clinically relevant genetic abnormalities, such as CBFB::MYH11 or inversion(16) [inv(16)], is critical for the diagnosis and management of patients with acute myeloid leukemia (AML). Notably, CBFB::MYH11 is a disease-defining mutation in AML and is associated with a favorable prognosis. The current standard-of-care workup, which includes a combination of conventional G-banding karyotyping, fluorescence in situ hybridization (FISH), and/or reverse-transcriptase PCR, poses challenges in detecting variant CBFB::MYH11 translocations. High-resolution, genome-wide technologies capable of accurate and unbiased detection of chromosomal structural aberrations at the gene/exon level, such as optical genome mapping (OGM), will be helpful for the timely detection of clinically actionable abnormalities. This case report presents a patient initially diagnosed with therapy-related myelodysplastic syndrome (MDS) following cytotoxic therapy and treated with a hypomethylating agent, who later experienced progression to AML with CBFB::MYH11 . Retrospective analysis of the initial diagnostic sample using OGM revealed a cryptic CBFB::MYH11 abnormality at the time of the first presentation. Furthermore, OGM enabled comprehensive characterization of this novel CBFB::MYH11 transcript with noncanonical breakpoints, which were not detected by standard molecular techniques. This case highlights a critical diagnostic blind spot in the detection of CBF::MYH11 AML, representing a missed opportunity to offer effective frontline therapy to a patient with potentially curable AML—an aberration not recognized by conventional karyotype or FISH at the time of initial diagnosis. The implementation of genome-wide technologies such as OGM as a first-tier diagnostic tool in clinical laboratories for the workup of MDS/AML is essential for detecting clinically impactful cryptic genomic alterations. The discovery of this novel alternate CBFB::MYH11 transcript with noncanonical breakpoints underscores a major limitation in current standard-of-care techniques, warranting further prospective studies to evaluate its clinical actionability in guiding personalized therapies.
Identification of targetable vulnerabilities of PLK1-overexpressing cancers by synthetic dosage lethality
Authors: Chelsea E Cunningham, Frederick S Vizeacoumar, Yue Zhang, Liliia Kyrylenko, Simon Both, Vincent Maranda, He Dong, Jared D W Price, Peng Gao, Konrad Wagner, Yingwen Wu, Mary Lazell-Wright, Ashtalakshmi Ganapathysamy, Rithik Hari, Kalpana K Bhanumathy, Connor Denomy, Anjali Saxena, Jeff P Vizeacoumar, Alain Morejon Morales, Faizaan Khan, Shayla Mosley, Angie Chen, Tetiana Katrii, Ben G E Zoller, Karthic Rajamanickam, Prachi Walke, Lihui Gong, Hardikkumar Patel, Hussain Elhasasna, Renuka Dahiya, Omar Abuhussein, Anton Dmitriev, Tanya Freywald, Erika Prando Munhoz, Eytan Ruppin, Joo Sang Lee, Katharina Rox, Martin Koebel, Laura Hopkins, Cheng Han Lee, Sunil Yadav, Gilles Gasparoni, Jörn Walter, Anand Krishnan, Raju Datla, Behzad Toosi, Kristi Baker, Jalna Meens, David W Cescon, Laurie Ailles, Scot C Leary, Yuliang Wu, Martin Empting, Alexandra K Kiemer, Andrew Freywald, Franco J Vizeacoumar
Journal: Cell Genomics (2025)

Chromosomal instability (CIN) drives tumor heterogeneity, complicating cancer therapy. Although Polo-like kinase 1 (PLK1) overexpression induces CIN, direct inhibition of PLK1 has shown limited clinical benefits. We therefore performed a genome-wide synthetic dosage lethality (SDL) screen to identify effective alternative targets and validated over 100 candidates using in vivo and in vitro secondary CRISPR screens. We employed direct-capture Perturb-seq to assess the transcriptional consequences and viability of each SDL perturbation at a single-cell resolution. This revealed IGF2BP2 as a critical genetic dependency that, when targeted, downregulated PLK1 and significantly restricted tumor growth. Mechanistic analyses showed that IGF2BP2 loss disrupted cellular energy metabolism and mitochondrial ATP production by downregulating PLK1 levels as well as genes associated with oxidative phosphorylation. Consistent with this, pharmacological inhibition of IGF2BP2 severely impacts the viability of PLK1-overexpressing cancer cells addicted to higher metabolic rates. Our work offers a novel therapeutic strategy against PLK1-driven heterogeneous malignancies.
Suppressing proteasome activity enhances sensitivity to actinomycin D in diffuse anaplastic Wilms tumor
Authors: Patricia D B Tiburcio, Kenian Chen, Lin Xu, Kenneth S Chen
Journal: Cell Reports Medicine (2025)

Wilms tumor is the most common pediatric kidney cancer, and diffuse anaplastic Wilms tumor is the most chemoresistant subtype. Here, we explore how Wilms tumor cells evade the chemotherapy actinomycin D, which inhibits ribosomal RNA biogenesis. Using ribosome profiling, protein arrays, and a genome-wide knockout screen, we describe how actinomycin D disrupts protein homeostasis and blocks cell-cycle progression. When ribosomal capacity is limited by actinomycin D treatment, anaplastic Wilms tumor cells preferentially translate proteasome components. Next, we find that the proteasome inhibitor bortezomib sensitizes cells to actinomycin D treatment in vitro and prolongs survival in xenograft models. Lastly, increased levels of proteasome components are associated with anaplastic histology and worse prognosis in Wilms tumor patients. In sum, maintaining protein homeostasis is critical for Wilms tumor proliferation, and it can be therapeutically disrupted by blocking protein synthesis or turnover.
RNAi-mediated silencing of SOD1 profoundly extends survival and functional outcomes in ALS mice
Authors: Alexandra Weiss, James W Gilbert, Iris Valeria Rivera Flores, Jillian Belgrad, Chantal Ferguson, Elif O Dogan, Nicholas Wightman, Kit Mocarski, Dimas Echeverria, Ashley L Harkins, Ashley Summers, Brianna Bramoto, Nicholas McHugh, Raymond Furgal, Nozomi Yamada, David Cooper, Kathryn Monopoli, Bruno M D C Godinho, Matthew R Hassler, Ken Yamada, Paul Greer, Nils Henninger, Robert H Brown, Anastasia Khvorova
Journal: Molecular Therapy (2025)

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative condition, with 20% of familial and 2-3% of sporadic cases linked to mutations in the cytosolic superoxide dismutase (SOD1) gene. Mutant SOD1 protein is toxic to motor neurons, making SOD1 gene suppression a promising approach, supported by preclinical data and the 2023 FDA approval of the GapmeR ASO targeting SOD1, tofersen. Despite the approval of an ASO and the optimism it brings to the field, the pharmacodynamics and pharmacokinetics of therapeutic SOD1 modulation can be improved. Here, we developed a chemically stabilized divalent siRNA scaffold (di-siRNA) that effectively suppresses SOD1 expression in vitro and in vivo. With optimized chemical modification, it achieves remarkable CNS tissue permeation and SOD1 silencing in vivo. Administered intraventricularly, di-siRNASOD1 extended survival in SOD1-G93A ALS mice, increasing survival beyond that previously seen in these mice by ASO modalities, slowed disease progression according to the standard ALS preclinical endpoints, and attenuated ALS neuropathology. These properties offer an improved therapeutic strategy for SOD1-mediated ALS and may extend to other dominantly inherited neurological disorders.
Reply: Survival benefit of transarterial chemoembolization combined with tyrosine kinase and immune checkpoint inhibitors as conversion therapy for unresectable hepatocellular carcinoma needs more details
Authors: Da-Long Yang, Yi-Fan Li, Yao-Jie Li, Guo-Gao Qiu, Zhi-Dong Liu, Yi-Ge Zhang, Huan Chen, Jian-Hong Zhong
Journal: Hepatology (2025)
Neuronal-targeted gene replacement rescues multiple phenotypes of STXBP1-related disorders in mice and is well-tolerated in nonhuman primates
Authors: Rangoli Aeran, Annie Tanenhaus, Sheila M S Sears, Nathan Moerke, Adam Miller, Camille Artur, Yosr Bouhlal, Peter F Bove, Alexander Diaz de Arce, Saki Shimizu, Jason Le, Keith Place, Dixon Hoffelt, Tselmeg Amarlkhagva, Jennifer Su, Ming Chen, Brooke Babineau, John McLaughlin, Myat Soe, Warren Macdonald, I Winnie Lin, Dhruv Bole, Kristen Valentine, Elizabeth Hallam, Puja Dhanota, Serena Liu, Steven A Tan, Ben Zhao, Raghavendra Hosur, Maria Candida Vila, Suresh Poda, Archana Belle, Stephanie Tagliatela
Journal: Molecular Therapy (2025)

De novo heterozygous variants in the neuronal STXBP1 gene cause severe, early-onset developmental and epileptic encephalopathy. Adeno-associated virus (AAV)-based gene replacement therapy offers the potential for a one-time, disease-modifying approach for STXBP1-related disorders. However, off-target overexpression in the liver and dorsal root ganglion (DRG) are known potential toxicities of AAV vectors. In addition, while loss of STXBP1 in GABAergic interneurons contributes to disease pathogenesis, typical gene therapy promoters do not express well in these cell populations. We engineered novel promoter cassettes to drive potent, selective STXBP1 expression across both excitatory and inhibitory neurons, and a 3'UTR regulatory element to detarget expression in DRG. Bilateral intracerebroventricular (ICV) injection of these promoter candidates achieved robust neuronal expression of STXBP1 and rescued key behavioral phenotypes in Stxbp1+/- haploinsufficient mice. In nonhuman primates, widespread vector biodistribution and transgene expression were observed in the central nervous system after unilateral ICV administration of AAV9-STXBP1 vectors. The vectors were well-tolerated, and addition of the detargeting regulatory element significantly reduced expression in DRG while ameliorating histopathologic effects and functional nerve conduction alterations. Taken together, these data support the feasibility of a one-time AAV-based therapeutic approach for STXBP1-related disorders.