tbuckley/cabot-search huggingface dataset:
Integrative proteo-transcriptomic characterization of advanced fibrosis in chronic liver disease across etiologies
Authors: Hong Yang, Dila Atak, Meng Yuan, Mengzhen Li, Ozlem Altay, Elif Demirtas, Ibrahim Batuhan Peltek, Burge Ulukan, Buket Yigit, Tarik Sipahioglu, María Bueno Álvez, Lingqi Meng, Bayram Yüksel, Hasan Turkez, Hale Kirimlioglu, Burcu Saka, Cihan Yurdaydin, Murat Akyildiz, Murat Dayangac, Mathias Uhlen, Jan Boren, Cheng Zhang, Adil Mardinoglu, Mujdat Zeybel
Journal: Cell Reports Medicine (2025)

Chronic hepatic injury and inflammation from various causes can lead to fibrosis and cirrhosis, potentially predisposing to hepatocellular carcinoma. The molecular mechanisms underlying fibrosis and its progression remain incompletely understood. Using a proteo-transcriptomics approach, we analyze liver and plasma samples from 330 individuals, including 40 healthy individuals and 290 patients with histologically characterized fibrosis due to chronic viral infection, alcohol consumption, or metabolic dysfunction-associated steatotic liver disease. Our findings reveal dysregulated pathways related to extracellular matrix, immune response, inflammation, and metabolism in advanced fibrosis. We also identify 132 circulating proteins associated with advanced fibrosis, with neurofascin and growth differentiation factor 15 demonstrating superior predictive performance for advanced fibrosis(area under the receiver operating characteristic curve [AUROC] 0.89 [95% confidence interval (CI) 0.81-0.97]) compared to the fibrosis-4 model (AUROC 0.85 [95% CI 0.78-0.93]). These findings provide insights into fibrosis pathogenesis and highlight the potential for more accurate non-invasive diagnosis.
Suspected and confirmed mpox cases in DR Congo: a retrospective analysis of national epidemiological and laboratory surveillance data, 2010–23
Authors: Eugene Bangwen, Ruth Diavita, Elise De Vos, Emmanuel Hasivirwe Vakaniaki, Sabin Sabiti Nundu, Annie Mutombo, Felix Mulangu, Aaron Aruna Abedi, Emile Malembi, Thierry Kalonji, Cris Kacita, Eddy Kinganda-Lusamaki, Tony Wawina-Bokalanga, Cécile Kremer, Isabel Brosius, Christophe Van Dijck, Emmanuel Bottieau, Koen Vercauteren, Adrienne Amuri-Aziza, Jean-Claude Makangara-Cigolo, Elisabeth Muyamuna, Elisabeth Pukuta, Beatrice Nguete, Didine Kaba, Joelle Kabamba, Christine M Hughes, Olivier Tshiani-Mbaya, Anne W Rimoin, Nicole A Hoff, Jason Kindrachuk, Niel Hens, Martine Peeters, Nicola Low, Andrea M McCollum, Robert Shongo, Daniel Mukadi-Bamuleka, Jean-Jacques Muyembe-Tamfum, Steve Ahuka-Mundeke, Laurens Liesenborghs, Placide Mbala-Kingebeni
Journal: The Lancet (2025)
EULAR/ACR classification criteria for paediatric chronic nonbacterial osteomyelitis (CNO)
Authors: Yongdong Zhao, Melissa S Oliver, Anja Schnabel, Eveline Y Wu, Zhaoyi Wang, Achille Marino, Cassyanne L Aguiar, Jonathan D Akikusa, Ummusen Kaya Akca, Beverley Almeida, Simone Appenzeller, Erin Balay-Dustrude, Ozge Basaran, Matthew L Basiaga, Yelda Bilginer, David A Cabral, Martina Capponi, Nathan Donaldson, Bugra Han Egeli, Emily J Fox, Antonella Insalaco, Ramesh S Iyer, Annette F Jansson, Inna Kostik, Mikhail Kostik, Leonard K Kovalick, Katia Tomie Kozu, Sivia K Lapidus, Tzielan C Lee, Aleksander Lenert, Kamran Mahmood, Edoardo Marrani, Doaa Mosad Mosa, Ian Muse, Alexander Mushkin, Katherine D Nowicki, Farzana Nuruzzaman, Karen Onel, Manuela Pardeo, Trang Sophia Pham, Lauren Potts, Athimalaipet V Ramanan, Angelo Ravelli, Nathan D Rogers, Andrew W Grim, Micol Romano, Natalie Rosenwasser, Takashi Shawn Sato, Gabriele Simonini, Jennifer B Soep, Sara M Stern, Timmy Strauss, Angela Taneja Kohli, Alexander C Theos, Lori B Tucker, Leslie F Vogel, Shima Yasin, Stephen C Wong, Katerina Bouchalova, Alison M Hendry, Kevin C Cain, Hermann J Girschick, Fatma Dedeoglu, Christian M Hedrich, Ronald M Laxer, Polly J Ferguson, Raymond Naden, Seza Ozen
Journal: Annals of the Rheumatic Diseases (2025)

The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal.
Association of walking with incident knee osteoarthritis: a prospective cohort study using data from the UK Biobank
Authors: Hongyi He, Yilun Wang, David Hunter, Yuqing Zhang, Weiya Zhang, Michael Doherty, Daniel K White, Jie Wei, Chao Zeng, Guanghua Lei
Journal: Annals of the Rheumatic Diseases (2025)

Walking offers numerous health benefits, yet its association with symptomatic knee osteoarthritis (SKOA) remains uncertain. The conflation of purposeful walking and unintentional walking could contribute to this uncertainty. Therefore, we aimed to examine the association between daily purposeful walking steps, daily unintentional walking steps, and total daily steps with incident SKOA. We conducted a population-based cohort study using data from the UK Biobank. Of the participants who had valid accelerometer data at baseline but no history of SKOA (identified through primary care or hospitalisation records), 89,969 were included. Hazard ratios (HRs) for categories of daily purposeful walking steps (cadence ≥60 steps/min), daily unintentional walking steps (cadence <60 steps/min), and total daily steps were estimated using a Cox proportional hazard model. The dose-response relationship was assessed using restricted cubic spline regression. During a mean follow-up of 6.85 (SD, 1.14) years, 2711 participants developed SKOA. For daily purposeful walking steps, HRs (95% CIs) of incident SKOA were 0.84 (0.76-0.92), 0.81 (0.71-0.90), and 0.74 (0.64-0.85) for those walking 4000 to 5999, 6000 to 7999, and ≥8000 steps/d, respectively, compared with those walking <4000 steps/d. Restricted cubic spline regression analysis revealed a declining curve with a potential threshold near 8000 steps/d. Conversely, more daily unintentional walking steps were significantly associated with higher incident SKOA. No significant association was observed for total daily steps. More daily purposeful walking steps were associated with lower incident SKOA, suggesting that purposeful walking may promote musculoskeletal health and help inform future guidelines for knee osteoarthritis prevention.
LLDAS and remission attainment with anifrolumab treatment in patients with systemic lupus erythematosus: results from the TULIP and long-term extension randomised controlled trials
Authors: Eric F Morand, Ronald van Vollenhoven, Richard A Furie, Kenneth C Kalunian, Susan Manzi, Gabriel Abreu, Raj Tummala, Elizabeth A Duncan, Hussein Al-Mossawi, Catharina Lindholm
Journal: Annals of the Rheumatic Diseases (2025)

To investigate the long-term impact of anifrolumab versus placebo on lupus low disease activity state (LLDAS) and definition of remission in systemic lupus erythematosus (DORIS) attainment in patients with systemic lupus erythematosus (SLE). This post hoc analysis included patients with moderate to severe SLE who were randomly assigned to receive intravenous anifrolumab 300 mg or placebo (once every 4 weeks) in the 52-week, phase 3 TULIP-1/TULIP-2 trials and continued with the same treatment in the 3-year long-term extension. LLDAS/DORIS rates over time were analysed using a stratified Cochran-Mantel-Haenszel approach and logistic regression. Time to first LLDAS/DORIS was estimated using Cox regression. Cumulative time and percentage of time in LLDAS/DORIS were assessed using an analysis of covariance. All P values are nominal. This analysis included 369 patients (anifrolumab n = 257, placebo n = 112). After 4 years of treatment (at Week 208), 36.9% of anifrolumab-treated patients versus 17.1% of placebo-treated patients were in LLDAS (odds ratio [OR], 2.7; 95% CI, 1.3-5.5; P = .0081); 30.3% versus 18.3% were in DORIS (OR, 1.9; 95% CI, 1.0-3.9; P = .0663). Time to first LLDAS and DORIS favoured anifrolumab versus placebo (LLDAS: hazard ratio, 1.56; 95% CI, 1.18-2.09; P = .0024; DORIS: hazard ratio, 1.50; 95% CI, 1.04-2.22; P = .0373). Cumulative time in LLDAS and DORIS was greater with anifrolumab than that with placebo (P = .0004 and P = .0032, respectively). LLDAS and DORIS remission, which are associated with favourable outcomes such as reduced damage and mortality in patients with SLE, are attainable and sustainable treatment targets with long-term anifrolumab treatment.
Author Correction: In vivo base editing extends lifespan of a humanized mouse model of prion disease
Authors: Meirui An, Jessie R. Davis, Jonathan M. Levy, Fiona E. Serack, John W. Harvey, Pamela P. Brauer, Catherine P. Pirtle, Kiara N. Berríos, Gregory A. Newby, Wei-Hsi Yeh, Nikita Kamath, Meredith Mortberg, Yuan Lian, Michael Howard, Kendrick DeSouza-Lenz, Kenia Guzman, Aaron Thai, Samantha Graffam, Vanessa Laversenne, Alissa A. Coffey, Jeannine Frei, Sarah E. Pierce, Jiri G. Safar, Benjamin E. Deverman, Eric Vallabh Minikel, Sonia M. Vallabh, David R. Liu
Journal: Nature Medicine (2025)
Revolutionizing tuberculosis treatment: Breakthroughs, challenges, and hope on the horizon
Authors: Martin Kufa, Vladimir Finger, Ondrej Kovar, Ondrej Soukup, Carilyn Torruellas, Jaroslav Roh, Jan Korabecny
Journal: Acta Pharmaceutica Sinica B (2025)

Tuberculosis (TB), an infectious disease caused by the bacterium Mycobacterium tuberculosis (Mtb), was responsible for the deaths of approximately 1.3 million people in 2022. In addition, 7.5 million new cases of TB have been reported. Present-day treatments require a daily dosing of a multiple-drug regimen for a minimum of six-month, but poor adherence and other factors often lead to treatment failure. Consequently, drug-resistant TB strains have become a growing concern, leading to more complex and expensive treatments. Promising drugs such as bedaquiline, delamanid, and pretomanid have been recently released, and 19 drug candidates are currently at different phases of clinical trials, addressing the problem of drug-resistant TB. Notwithstanding recent advances, the development of effective and safe drugs with novel mechanisms of action remains a challenge due to the unique nature of Mtb. Despite the persistent need for new treatments, TB research remains underfunded, highlighting the importance of collaborations between academia and the private sector in the advancement of anti-TB drug development. This review provides a perspective on the dynamic landscape of anti-TB drug discovery in recent years, offering hope for a more effective approach to combat this persistent global health threat.
Standard enhancement settings used on endoscopy systems significantly impair performance of artificial intelligence systems in endoscopy.
Authors: Martijn R. Jong, Carolus H.J. Kusters, Querijn N.E. van Bokhorst, Jelmer B. Jukema, Rixta A.H. van Eijck van Heslinga, Kiki N. Fockens, Britt B.S.L. Houwen, Tim J.M. Jaspers, Tim G.W. Boers, Manon van der Vlugt, Evelien Dekker, Fons van der Sommen, Peter H.N. de With, Albert Jeroen De Groof, Jacques Bergman
Journal: Endoscopy (2025)

Background AI-systems in endoscopy are predominantly developed and tested using high-quality imagery from expert centers. Their performance may be different when applied on heterogeneous imagery in clinical practice. This is partially caused by the diversity in post-processing enhancement settings used in endoscopy units. We evaluated the impact of post-processing enhancement settings on AI performance and tested specific data augmentation strategies to mitigate performance loss. Methods We used a computer-aided detection (CADe) system for Barrett’s neoplasia (6,223 images, 906 patients) and a computer-aided diagnosis (CADx) system for colorectal polyps (3,288 images, 969 patients), both trained on datasets acquired with Olympus equipment. First, systems were trained using their original datasets, which were acquired with limited variability in enhancement settings. These CAD systems were then tested across a wide range of test sets, which comprised the same images, but displayed with different enhancement settings. Then, both CAD systems were retrained using image enhancement-based data augmentation. The performance of these adjusted CAD systems was then evaluated on the same array of test sets. Results When trained on their original training set and tested over a range of enhancement settings, both systems displayed substantial performance variability: 83-92% sensitivity and 84-91% specificity for CADe; 78-85% sensitivity and 45-63% specificity for CADx. After retraining CAD systems using image enhancement-based data augmentation, variability in sensitivity and specificity was reduced to 2% (p&gt;0.001) and 1% (p=0.003) for CADe and 2% (p=0.029) and 8% (p=0.190) for CADx. Conclusion This retrospective study indicates that performance of current endoscopic AI systems can substantially vary depending on the post-processing enhancement settings of the endoscopy unit. Specific data augmentation can mitigate this performance loss.
Discovery of a potential hematologic malignancies therapy: Selective and potent HDAC7 PROTAC degrader targeting non-enzymatic function
Authors: Yuheng Jin, Xuxin Qi, Xiaoli Yu, Xirui Cheng, Boya Chen, Mingfei Wu, Jingyu Zhang, Hao Yin, Yang Lu, Yihui Zhou, Ao Pang, Yushen Lin, Li Jiang, Qiuqiu Shi, Shuangshuang Geng, Yubo Zhou, Xiaojun Yao, Linjie Li, Haiting Duan, Jinxin Che, Ji Cao, Qiaojun He, Xiaowu Dong
Journal: Acta Pharmaceutica Sinica B (2025)

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.
Antibody-secreting cell repertoires hold high-affinity anti-rocuronium specificities that can induce anaphylaxis in vivo
Authors: Alice Dejoux, Qianqian Zhu, Adam Woolfe, Ophélie Godon, Sami Ellouze, Guillaume Mottet, Carlos Castrillon, Caitlin Gillis, Cyprien Pecalvel, Christelle Ganneau, Bruno Iannascoli, Frédéric Lemoine, Frederick Saul, Patrick England, Laurent L Reber, Aurélie Gouel-Chéron, Luc de Chaisemartin, Ahmed Haouz, Gaël A Millot, Sylvie Bay, Annabelle Gérard, Friederike Jönsson, Sylvie Chollet-Martin, Pierre Bruhns
Journal: Journal of Allergy and Clinical Immunology (2025)

Neuromuscular blocking agents (NMBA) are muscle relaxants used to assist mechanical ventilation but lead in 1/10,000 anesthesia to severe acute hypersensitivity reactions i.e., anaphylaxis. Incidences vary between types of NMBAs. Rocuronium, a widely used non-depolarizing aminosteroid NMBA, induces among the highest anaphylaxis rates. Rocuronium-induced anaphylaxis is proposed to rely on pre-existing rocuronium-binding antibodies, but no such antibodies have ever been identified. Identify rocuronium-specific antibody repertoires from plasma cells or plasmablasts of rocuronium-immunized mice, and determine the affinities, structures and anaphylactogenic potential of these antibodies for rocuronium. Herein, we engrafted rocuronium onto carrier proteins allowing immunization of mice against rocuronium, screening for rocuronium-specific antibody responses, and sorting of rocuronium-specific plasma cells using droplet microfluidics coupled to single-cell antibody gene (VH and VL) sequencing. The two different repertoires of >500 VH-VL pairs were oligoclonal, comprised of three major clonal families, and displayed convergence. Expressed as human IgG1, these antibodies demonstrated subnanomolar affinities for rocuronium with families either monospecific for rocuronium or cross-reactive only for closely-related NMBAs. Expressed as human IgE, they triggered human mast cell and basophil activation, and severe passive systemic anaphylaxis in mice humanized for the IgE receptor FcεRI. Co-crystal structures between rocuronium and antibody representatives of three different VH-VL families revealed distinct interaction modes with, however, the ammonium group involved systematically in the binding interface. This work identifies the epitopes of antibody reactivity to rocuronium, demonstrates anaphylactogenic potential of anti-rocuronium IgE and establishes the first mouse model of NMBA anaphylaxis.
MRD-guided zanubrutinib, venetoclax and obinutuzumab in relapsed CLL: primary endpoint analysis from the CLL2-BZAG trial
Authors: Moritz Fürstenau, Sandra Robrecht, Christof Schneider, Eugen Tausch, Adam Giza, Matthias Ritgen, Jörg T Bittenbring, Holger Hebart, Björn Schöttker, Anna Lena Lena Illert, Ullrich Graeven, Andrea Stoltefuss, Bernhard Heinrich, Robert Eckert, Anna-Maria Fink, Janina Stumpf, Kirsten Fischer, Othman Al-Sawaf, Florian Simon, Fanni Kleinert, Jonathan Weiss, Karl-Anton Kreuzer, Anke Schilhabel, Monika Brüggemann, Petra Langerbeins, Stephan Stilgenbauer, Barbara Eichhorst, Michael J Hallek, Paula Cramer
Journal: Blood (2025)
Bi-directional communication between intrinsic enteric neurons and ILC2s inhibits host defense against helminth infection
Authors: Yinsheng Wang, Xiaoyu Zhang, Shaorui Liu, Zhijie Gu, Zijia Sun, Yang Zang, Xiaobao Huang, Yi Wang, Qiang Wang, Qingxia Lin, Ruichao Liu, Suhua Sun, Hongkai Xu, Jiali Wang, Tao Wu, Yan Wang, Yu Li, Hui Li, Zirun Tang, Yifan Qu, Li Wu, Xiaoyu Hu, Xiaohuan Guo, Fang Wang, Lei Zhou, Danyang He, Hai Qi, Heping Xu, Coco Chu
Journal: Immunity (2025)
Digital twin driven electrode optimization for wearable bladder monitoring via bioimpedance
Authors: H Trask Crane, John A Berkebile, Samer Mabrouk, Nicholas Riccardelli, Omer T Inan
Journal: npj Digital Medicine (2025)

Monitoring fluid intake and output for congestive heart failure (CHF) patients is an essential tool to prevent fluid overload, a principal cause of hospital admissions. Addressing this, bladder volume measurement systems utilizing bioimpedance and electrical impedance tomography have been proposed, with limited exploration of continuous monitoring within a wearable design. Advancing this format, we developed a conductivity digital twin from radiological data, where we performed exhaustive simulations to optimize electrode sensitivity on an individual basis. Our optimized placement demonstrated an efficient proof-of-concept volume estimation that required as few as seven measurement frames while maintaining low errors (CI 95% -1.11% to 1.00%) for volumes ≥100 mL. Additionally, we quantify the impact of ascites, a common confounding condition in CHF, on the bioimpedance signal. By improving monitoring technology, we aim to reduce CHF mortality by empowering patients and clinicians with a more thorough understanding of fluid status.
GATA2 mutated allele specific expression is associated with a hyporesponsive state of HSC in GATA2 deficiency syndrome
Authors: Laetitia Largeaud, Vincent Fregona, Laura A Jamrog, Camille Hamelle, Stéphanie Dufrechou, Naïs Prade, Esmaa Sellam, Pauline Enfedaque, Manon Bayet, Sylvie Hébrard, Mathieu Bouttier, Christine Didier, Bastien Gerby, Eric Delabesse, Marlène Pasquet, Cyril Broccardo
Journal: Blood Cancer Journal (2025)

GATA2 germline mutations lead to a syndrome characterized by immunodeficiency, vascular disorders and myeloid malignancies. To elucidate how these mutations affect hematopoietic homeostasis, we created a knock-in mouse model expressing the recurrent Gata2 R396Q missense mutation. Employing molecular and functional approaches, we investigated the mutation's impact on hematopoiesis, revealing significant alterations in the hematopoietic stem and progenitor (HSPC) compartment in young age. These include increased LT-HSC numbers, reduced self-renewal potential, and impaired response to acute inflammatory stimuli. The mature HSPC compartment was primarily affected at the CMP sub-population level. In the mutant LT-HSC population, we identified an aberrant subpopulation strongly expressing CD150, resembling aging, but occurring prematurely. This population showed hyporesponsiveness, accumulated over time, and exhibited allele-specific expression (ASE) favoring the mutated Gata2 allele, also observed in GATA2 mutated patients. Our findings reveal the detrimental impact of a Gata2 recurrent missense mutation on the HSC compartment contributing to its functional decline. Defects in the CMP mature compartment, along with the inflammatory molecular signature, explain the loss of heterogeneity in HPC compartment observed in patients. Finally, our study provides a valuable model that recapitulates the ASE-related pathology observed in GATA2 deficiency, shedding light on the mechanisms contributing to the disease's natural progression.
Glucocorticoid receptor suppresses GATA6-mediated RNA polymerase II pause release to modulate classical subtype identity in pancreatic cancer
Authors: Thomas L Ekstrom, Raya M Rosok, Amro M Abdelrahman, Christina Parassiadis, Meghana Manjunath, Marianna Y Dittrich, Xin Wang, Ana P Kutschat, Akshay Kanakan, Ashish Rajput, Nadine Schacherer, Teodora Lukic, Danielle M Carlson, Julia Thiel, Waltraut Kopp, Philipp Stroebel, Volker Ellenrieder, Jochen Gaedcke, Meng Dong, Zeynab Najafova, Mark J Truty, Elisabeth Hessmann, Steven A Johnsen
Journal: Gut (2025)

Background Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer with a 5-year survival rate of 12%. It has two major molecular subtypes: classical and basal, regulated by the master transcription factors (MTFs) GATA6 and ΔNp63, respectively. Objective This study sought to uncover the transcriptional regulatory mechanisms controlling PDAC subtype identity. Design We integrated primary tumour single-cell RNA-seq, patient-derived xenograft RNA-seq and multispectral imaging to identify MTF-dependent, subtype-specific markers. We created subtype-specific fluorescent reporter systems and conducted drug screenings to find actionable targets. We analysed chromatin accessibility (ATAC-seq), genome-wide occupancy (ChIP-seq) for epigenetic status (H3K27ac), MTFs (GATA6, ΔNp63), RNA polymerase II (Pol II), H3K4me3-anchored chromatin topology (HiChIP) and nascent RNA capture sequencing (PRO-seq). Additionally, we used nuclease-dead Cas9 (dCas9) to manipulate transcriptional regulatory mechanisms. Results Our approach identified glucocorticoid receptor (GR) agonists as agents that suppress the classical transcriptional programme by interacting with GATA6. GATA6 regulates classical-specific transcription through promoter-proximal pause release. Depletion of GATA6 increased Pol II occupancy at GATA6-bound enhancers and transcriptional start sites, stabilising enhancer–promoter interactions. Artificially inducing pausing at GATA6-bound enhancers with dCas9 abrogated target gene expression and induced pausing at both the enhancer and target gene promoter. Conversely, in basal PDAC ΔNp63 promotes Pol II recruitment and stabilises enhancer–promoter interactions. Conclusion This study provides new insights into the transcriptional control and role of GR agonists in controlling PDAC molecular subtype identity.