tbuckley/cabot-search huggingface dataset:
Efficacy and Safety of Higher Doses of Levofloxacin for MDR-TB: A Randomized Placebo-controlled Phase 2 Trial
Authors: Patrick PJ Phillips, Charles A Peloquin, Timothy R. Sterling, Pawandeep Kaur, Andreas H. Diacon, Eduardo Gotuzzo, Debra Benator, Robin M. Warren, David Sikes, Leonid Lecca, Neel R Gandhi, Elizabeth M Streicher, Nancy Dianis, Kathleen Eisenach, Carole D. Mitnick, C. Robert Horsburgh
Journal: American Journal of Respiratory and Critical Care Medicine (2025)

Background: Evaluation of optimal dosing has generally been inadequate during TB drug development. Fluoroquinolones are central to TB treatment. We aimed to determine the dose of levofloxacin needed to achieve maximal efficacy and acceptable safety and tolerability as part of a multidrug TB regimen. Methods: Opti-Q was an international, multi-center, randomized, placebo-controlled, phase II trial. Eligible participants with TB resistant to isoniazid and rifampicin but susceptible to fluoroquinolones (MDR-TB) were randomized to receive one of four weight-adjusted once-daily doses of levofloxacin given for 24 weeks(168 doses): 11mg/kg(750mg), 14mg/kg(750mg/1000mg), 17 mg/kg(1000mg/1250mg) or 20mg/kg(1250mg/1500mg) alongside a multidrug regimen. The primary efficacy outcome was time to sputum culture conversion and the primary safety outcome was grade 3 or higher adverse events. Findings: 111 participants were randomized from three sites in South Africa and Peru. 83(75%) had cavities on chest x-ray, 55(50%) had a smear grading of 3+, median BMI was 20.4 kg/m2. Median levofloxacin AUC/MIC was 573, 633, 918 and 1343 across the four treatment arms. There was no difference in time to culture conversion on solid or liquid media by treatment arm (stratified log-rank p=0.282), by tertile of AUC/MIC (p=0.350), or by dose received (p=0.723); 69.3%, 74.8%, 70.6% and 78.3% achieved culture conversion after 8 weeks on solid media respectively across the treatment arms; 64.6%, 69.5%, 52.6% and 69.6% in liquid culture. More participants experienced a grade 3-5 adverse event by dose (37.0% and 16.0% in the highest and lowest dose groups respectively, p=0.042, Cochran-Armitage test for trend) and by tertile of AUC (p=0.011). Interpretation: As part of a multidrug regimen, doses of levofloxacin above 1000mg resulted in greater exposures and increased frequency of adverse events but did not result in faster time to sputum culture conversion. A dose of 1000mg daily can achieve the target exposure in nearly all adults and was well tolerated. Clinical trial registration available at www.clinicaltrials.gov, ID: NCT01918397
Letter to the Editor: Fiber and whole grain intakes in relation to liver cancer risk: An analysis in 2 prospective cohorts and systematic review and meta-analysis of prospective studies
Authors: Wang Huang, Hao Sun
Journal: Hepatology (2025)

Department of Gastrointestinal Surgery, Chongqing University Cancer Hospital, Chongqing, 400030, China Correspondence Hao Sun; No. 181 Hanyu Road, Shapingba District, Chongqing 400030, P.R. China. Email: [email protected].
Pre-B-Cell leukemia transcription factor 1 contributes to liver fibrosis by enabling IL-7 signaling in hepatic stellate cells
Authors: Qianwen Zhao, Hong Liu, Zhen Yang, Xingxing Han, Aoqi Kang, Hao Li, Wenjing Ren, Qianqian Chen, Yue Huan, Yong Xu, Jie Li, Ming Kong, Zilong Li
Journal: Hepatology (2025)

Background and Aims: Liver fibrosis, when dysregulated, contributes to irreversible loss of hepatic structure and function heralding end-stage liver diseases including cirrhosis and hepatocellular carcinoma. Hepatic stellate cells (HSCs) represent the common progenitor to myofibroblasts that produce extracellular matrix (ECM) proteins to mediate liver fibrosis. In the present study, we investigated the role of Pre-B-Cell leukemia transcription factor 1 (PBX1) in this process. Methods: Liver fibrosis was induced by CCl 4 injection or bile duct ligation (BDL). Cellular transcriptome was examined by RNA-seq and CUT&amp;Tag-seq. Results: PBX1 was screened out of mining through liver fibrosis-related single-cell RNA-seq datasets as the most prominently up-regulated transcription factor during HSC activation. Ingenuity pathway analysis (IPA) coupled with reporter assay and ChIP assay demonstrated that Notch3 mediated elevation of PBX1 expression at the transcriptional level in HSCs. PBX1 knockdown attenuated HSC-myofibroblast transition in vitro and liver fibrosis in mice. Integrated transcriptomic analysis suggested that PBX1 contributed to HSC activation by activating a host of pro-fibrogenic molecules including interleukin 7 receptor (IL7R/CD127). Consistently, exposure to recombinant IL-7 promoted HSC activation whereas IL7R knockdown hampered HSC activation. Mechanistically, IL7R interacted with TGF-β receptors (TβRI/II) to trigger a pro-fibrogenic signaling cascade. Importantly, blockade of the IL-7-IL7R signaling with neutralizing antibodies markedly ameliorated liver fibrosis in mice. Finally, a positive correlation between PBX1, IL7R and HSC activation was identified in cirrhotic patients. Conclusions: Our data uncover a previously unappreciated role for PBX1 in HSC activation and provide proof-of-concept for targeting IL-7 signaling in the intervention of liver fibrosis.
Global 10 year ecological momentary assessment and mobile sensing study on tinnitus and environmental sounds
Authors: Robin Kraft, Berthold Langguth, Jorge Simoes, Manfred Reichert, Winfried Schlee, Rüdiger Pryss
Journal: npj Digital Medicine (2025)

Abstract In most tinnitus patients, tinnitus can be masked by external sounds. However, evidence for the efficacy of sound-based treatments is scarce. To elucidate the effect of sounds on tinnitus under real-world conditions, we collected data through the TrackYourTinnitus mobile platform over a ten-year period using Ecological Momentary Assessment and Mobile Crowdsensing. Using this dataset, we analyzed 67,442 samples from 572 users. Depending on the effect of environmental sounds on tinnitus, we identified three groups (T-, T+, T0) using Growth Mixture Modeling (GMM). Moreover, we compared these groups with respect to demographic, clinical, and user characteristics. We found that external sound reduces tinnitus (T-) in about 20% of users, increases tinnitus (T+) in about 5%, and leaves tinnitus unaffected (T0) in about 75%. The three groups differed significantly with respect to age and hearing problems, suggesting that the effect of sound on tinnitus is a relevant criterion for clinical subtyping.
Holistic AI analysis of hybrid cardiac perfusion images for mortality prediction
Authors: Anna M. Marcinkiewicz, Wenhao Zhang, Aakash Shanbhag, Robert J. H. Miller, Mark Lemley, Giselle Ramirez, Mikolaj Buchwald, Aditya Killekar, Paul B. Kavanagh, Attila Feher, Edward J. Miller, Andrew J. Einstein, Terrence D. Ruddy, Joanna X. Liang, Valerie Builoff, David Ouyang, Daniel S. Berman, Damini Dey, Piotr J. Slomka
Journal: npj Digital Medicine (2025)

Abstract Low-dose computed tomography attenuation correction (CTAC) scans are used in hybrid myocardial perfusion imaging (MPI) for attenuation correction and coronary calcium scoring, and contain additional anatomic and pathologic information not utilized in clinical assessment. We seek to uncover the full potential of these scans utilizing a holistic artificial intelligence (AI) approach. A multi-structure model segmented 33 structures and quantified 15 radiomics features in each organ in 10,480 patients from 4 sites. Coronary calcium and epicardial fat measures were obtained from separate AI models. The area under the receiver-operating characteristic curves (AUC) for all-cause mortality prediction of the model utilizing MPI, CT, stress test, and clinical features was 0.80 (95% confidence interval [0.74–0.87]), which was higher than for coronary calcium (0.64 [0.57–0.71]) or perfusion (0.62 [0.55–0.70]), with p &lt; 0.001 for both. A comprehensive multimodality approach can significantly improve mortality prediction compared to MPI information alone in patients undergoing hybrid MPI.
Effect of computer aided detection system on esophageal neoplasm diagnosis in varied levels of endoscopists
Authors: Bing Li, Yan-Yun Du, Wei-Min Tan, Dong-Li He, Zhi-Peng Qi, Hon-Ho Yu, Qiang Shi, Zhong Ren, Ming-Yan Cai, Bo Yan, Shi-Lun Cai, Yun-Shi Zhong
Journal: npj Digital Medicine (2025)

A computer-aided detection (CAD) system for early esophagus carcinoma identification during endoscopy with narrow-band imaging (NBI) was evaluated in a large-scale, prospective, tandem, randomized controlled trial to assess its effectiveness. The study was registered at the Chinese Clinical Trial Registry (ChiCTR2100050654, 2021/09/01). Involving 3400 patients were randomly assigned to either routine (routine-first) or CAD-assisted (CAD-first) NBI endoscopy, followed by the other procedure, with targeted biopsies taken at the end of the second examination. The primary outcome was the diagnosis of 1 or more neoplastic lesion of esophagus during the first examination. The CAD-first group demonstrated a significantly higher neoplastic lesion detection rate (3.12%) compared to the routine-first group (1.59%) with a relative detection ratio of 1.96 (P = 0.0047). Subgroup analysis revealed a higher detection rate in junior endoscopists using CAD-first, while no significant difference was observed for senior endoscopists. The CAD system significantly improved esophageal neoplasm detection, particularly benefiting junior endoscopists.
Basophil-VAMP7 is A Vital Regulator of Skin Barrier Integrity and Chronic Itch
Authors: Wenhao Zhang, Xiaolong Dai, Weiwei Chen, Yanqing Li, Huiyuan Mei, Jorg Buddenkotte, Xingyun Zhu, Martin Steinhoff, Jiafu Wang, Jianghui Meng
Journal: Journal of Allergy and Clinical Immunology (2025)
Child Opportunity Index at Birth and Asthma with Recurrent Exacerbations in the U.S. ECHO Program
Authors: Rachel L Miller, Holly Schuh, Aruna Chandran, Rima Habre, Jyoti Angal, Izzuddin M Aris, Judy L Aschner, Casper G Bendixsen, Jeffrey Blossom, Michelle Bosquet-Enlow, Carrie V Breton, Carlos A Camargo, Kecia N Carroll, Sarah Commodore, Lisa A Croen, Dana M Dabelea, Sean C L Deoni, Assiamira Ferrara, Rebecca C Fry, Jody M Ganiban, Sarah D Geiger, James E Gern, Frank D Gilliland, Semsa Gogcu, Diane R Gold, Marion E Hare, Robyn N Harte, Tina V Hartert, Irva Hertz-Picciotto, Alison E Hipwell, Daniel J Jackson, Margaret K Karagas, Gurjit K Khurana Hershey, Haejin Kim, Augusto A Litonjua, Carmen J Marsit, Cynthia T McEvoy, Eneida A Mendonça, Paul E Moore, Anh P Nguyen, Flory L Nkoy, Thomas G O'Connor, Emily Oken, Dennis R Ownby, Matthew Perzanowski, Katherine Rivera-Spoljaric, Sheela Sathyanarayana, Anne Marie Singh, Joseph B Stanford, Annemarie Stroustrup, Nissa Towe-Goodman, Veronica A Wang, Tracey J Woodruff, Robert O Wright, Rosalind J Wright, Antonella Zanobetti, Edward M Zoratti, Christine C Johnson
Journal: Journal of Allergy and Clinical Immunology (2025)
Oral ADC189 for Adults and Adolescents with Uncomplicated Influenza
Authors: Jingya Zhao, Guoping Sheng, Yingqi Lyu, Yilan Sun, Sikui Wang, Xiaolin Chen, Feng Ye, Lin Chen, Xiaowei Xu, Hong Wang, Bin Wu, Chunxian Peng, Min Deng, Lihong Qu, Xuehong Jiang, Junyan Hu, Yan Feng, Yongzhong Li, Jie Peng, Weiyang Li, Lei Shao, Feng Gao, Dongbo Tian, Jie Tan, Huanwei Zheng, Meifang Chen, Hong Wu, Xiaoyun Zhu, Min Zhou, Jieming Qu
Journal: Journal of Infection (2025)

ADC189 is a novel anti-influenza virus inhibitor. In this study, we aimed to evaluated the safety and efficacy of ADC189 in outpatients with uncomplicated influenza infection. In the phase 2 trial, we assigned patients in a 2:2:1 ratio to receive either single dose 15-mg or 45-mg of ADC189 or placebo. In the phase 3 part, participants were randomized in a 2:1 ratio to receive 45-mg of ADC189 or placebo. The primary end point was the time to alleviation of influenza symptoms in the intention-to-treat infected population. In the phase 2 trial that had 150 participants, the median time for virus RNA clearance was shorter in both ADC189 groups (15-mg group, 50·7hours; 45 mg-group, 45·8hours) compared to the placebo group (73·4hours; p=0·69 and 0·016, respectively). 617 participants were enrolled in the phase 3 trial. The median time to symptom alleviation was 50·0hours (95% CI, 44·6 to 59·3) with ADC189, as compared with 68·1hours (95% CI, 62·8 to 84·4) with placebo (p<0·0001). By 1 day after initiation, the decrease in viral load from baseline was greater in the ADC189 group than in the placebo group (2·316 and 1·049 log10 virus copies per milliliter, respectively). Most adverse events were mild or moderate. A single-dose ADC189 shorten the time to the resolution of symptoms among adults and adolescents with uncomplicated influenza, without evident safety concerns. (Funded by Jiaxing AnDiCon Biotech Co., Ltd, Zhejiang, China; ChiCTR number, 20230137, and ClinicalTrials. gov number, NCT06342921.).
Safety and activity of talquetamab in patients with relapsed or refractory multiple myeloma (MonumenTAL-1): a multicentre, open-label, phase 1–2 study
Authors: Ajai Chari, Cyrille Touzeau, Carolina Schinke, Monique C Minnema, Jesus G Berdeja, Albert Oriol, Niels W C J van de Donk, Paula Rodríguez-Otero, Daniel Morillo, Carmen Martinez-Chamorro, María-Victoria Mateos, Luciano J Costa, Jo Caers, Leo Rasche, Amrita Krishnan, Jing Christine Ye, Lionel Karlin, Brea Lipe, Deeksha Vishwamitra, Sheri Skerget, Raluca Verona, Xuewen Ma, Xiang Qin, Hein Ludlage, Michela Campagna, Tara Masterson, Brandi Hilder, Jaszianne Tolbert, Thomas Renaud, Jenna D Goldberg, Colleen Kane, Christoph Heuck, Jesus San-Miguel, Philippe Moreau
Journal: The Lancet Haematology (2025)
Software-based versus visual assessment of the minimal ablative margin in patients with liver tumours undergoing percutaneous thermal ablation (COVER-ALL): a randomised phase 2 trial
Authors: Bruno C Odisio, Jessica Albuquerque, Yuan-Mao Lin, Brian M Anderson, Caleb S O'Connor, Bastien Rigaud, Maria Briones-Dimayuga, Aaron K Jones, Bryan M Fellman, Steven Y Huang, Joshua Kuban, Zeyad A Metwalli, Rahul Sheth, Peiman Habibollahi, Milan Patel, Ketan Y Shah, Veronica L Cox, HyunSeon C Kang, Van K Morris, Scott Kopetz, Milind M Javle, Ahmed Kaseb, Ching-Wei Tzeng, Hop-Tran Cao, Timothy Newhook, Yun Shin Chun, Jean-Nicolas Vauthey, Sanjay Gupta, Iwan Paolucci, Kristy K Brock
Journal: The Lancet. Gastroenterology & hepatology (2025)
Talicabtagene autoleucel for relapsed or refractory B-cell malignancies: results from an open-label, multicentre, phase 1/2 study
Authors: Hasmukh Jain, Atharva Karulkar, Devanshi Kalra, Smrithi Ravikumar, Shreshtha Shah, Afrin Firfiray, Juber Pendhari, Ankesh Kumar Jaiswal, Aalia Khan, Manivasagam Sundharam, Anand Vaibhaw, Ashish Saroha, Shreewardhan Rajyopadhye, Moumita Basu, Sweety Asija, Ambalika Chowdhury, Rohit Beher, Ankit Banik, Alka Dwivedi, Shalini Purwar, Gaurav Narula, Shripad Banavali, Nitin Jain, Steven L Highfill, David Stroncek, Terry Fry, Sameer Melinkeri, Lovin Wilson, Narendra Agarwal, Anil Aribandi, Pavan Kumar Boyella, Nirali N Shah, Sattva S Neelapu, Manju Sengar, Rahul Purwar
Journal: The Lancet Haematology (2025)
A call for health R&amp;D prioritisation and governance mechanisms in Africa
Authors: Mosoka Papa Fallah, Nebiyu Dereje, Elvis Temfack, Dathan M Byonanebye, Jacqueline Weyer, Polydor Ngoy Mutombo, Wayengera Misaki, Eastman Candace, Alhaji Njai, Nathalie Strub-Wourgaft, Nelson Sewankambo, Adu-Sarkodie Yaw, Placide Mbala-Kingebeni, Dougbeh-Chris Nyan, Birkneh Tilahun Tadesse, Christof Vinnemeier, Luis Sambo, Isaac Adewole, Raji Tajudeen, Jean Kaseya
Journal: The Lancet (2025)
Hepatitis B core-related antigen rapid diagnostic test for point-of-care identification of women at high risk of hepatitis B vertical transmission: a multicountry diagnostic accuracy study
Authors: Jeanne Perpétue Vincent, Olivier Ségéral, Dramane Kania, Laurence Borand, Jean-Pierre Adoukara, Adeline Pivert, Amariane Koné, Abdoul Salam Eric Tiendrebeogo, Haoua Tall, Laura Schaeffer, Muriel Vray, Armel Moumouni Sanou, Richard Njouom, Gavin Cloherty, Naofumi Hashimoto, Tetsuo Miura, Wataru Sugiura, Saren Sovann, Jee-Seon Yang, Gauthier Delvallez, Françoise Lunel-Fabiani, Yasuhito Tanaka, Yusuke Shimakawa
Journal: The Lancet. Gastroenterology & hepatology (2025)
Immunophenotype of CAR T-cells and associated apheresis products predicts clinical response in a single-center CD22 CAR T-cell therapy trial in B-cell acute lymphoblastic leukemia
Authors: Alexandra Dreyzin, Lipei Shao, Yihua Cai, Kyu Lee Han, Michaela Prochazkova, Michael Gertz, Bonnie Yates, Rongye Shi, Kathryn Martin, Naomi Taylor, Steven Highfill, Maura O'Neill, Thorkell Andresson, David Stroncek, Ping Jin, Nirali N Shah
Journal: Molecular Therapy (2025)
Proton Pump Inhibitors for Inducing and Maintaining Remission in Eosinophilic Esophagitis: An Updated Systematic Review and Meta-Analysis
Authors: Alfredo J Lucendo, Lucía Gutiérrez-Ramírez, Antonio Tejera-Muñoz, Javier Molina-Infante, Ángel Arias
Journal: Clinical Gastroenterology and Hepatology (2025)
Risk of age-related and disease-related complications and mortality in elderly-onset IBD - a population-based study
Authors: Dana Ben Hur, Guy Issaschar, Ran Moshe, Boris Lebedenko, Rona Lujan, Ziona Haklai, Yiska Loewenberg Weisband, Amir Ben-Tov, Natan Lederman, Eran Matz, Iris Dotan, Dan Turner, Gabriel D Pinto, Matti Waterman
Journal: Clinical Gastroenterology and Hepatology (2025)
Self-knowledge distillation-empowered directional connectivity transformer for microbial keratitis biomarkers segmentation on slit-lamp photography
Authors: Ziyun Yang, Maria A Woodward, Leslie M Niziol, Mercy Pawar, N Venkatesh Prajna, Anusha Krishnamoorthy, Yiqing Wang, Ming-Chen Lu, Suvitha Selvaraj, Sina Farsiu
Journal: Medical Image Analysis (2025)
CD47 Peptide-Cloaked Lipid Nanoparticles Promote Cell-Specific mRNA Delivery
Authors: Tyler Ellis Papp, Jianhao Zeng, Hamna Shahnawaz, Awurama Akyianu, Laura Breda, Amir Yadegari, Joseph Steward, Ruiqi Shi, Qin Li, Barbara L Mui, Ying K Tam, Drew Weissman, Stefano Rivella, Vladimir Shuvaev, Vladimir R Muzykantov, Hamideh Parhiz
Journal: Molecular Therapy (2025)
Long-term Cardiovascular Safety of Ustekinumab in Psoriasis and Psoriatic Arthritis: Results from an Observational Post-Authorization Safety Study Based on Swedish National Registers
Authors: Jonas Banefelt, Helena Skröder, Ahlem Azzabi, Anna Sheahan, Robert Suruki, Anja Geldhof
Journal: Journal of the American Academy of Dermatology (2025)
Codelivery Ce6 and curcumin in antibacterial poly(β-amino ester) for anti-inflammatory and photodynamic antimicrobial combination therapy
Authors: Chong Liu, Lei Guo, Penghan Yue, Dayang Xie, Jahui Gao, Yanwei Li, Cong Liu, Caina Xu, Yanhui Li, Huayu Tian
Journal: Journal of Controlled Release (2025)
Antibiotic chemoprophylaxis for close contacts of invasive group A streptococcus in community settings: evidence review
Authors: Vicky Watts, Martine Usdin, Rachel Mearkle, Shiranee Sriskandan, Rebecca Cordery, Sally Millership, Vanessa Saliba, Claire Edmundson, Anjali Pai, Colin S Brown, Sooria Balasegaram, Theresa Lamagni, Valerie Decraene
Journal: Journal of Infection (2025)
Long-term risk of psychiatric disorders in childhood and adolescence following neonatal invasive group B Streptococcus disease—a Danish cohort study
Authors: Malene Risager Lykke, Henrik Toft Sørensen, Joy Elisabeth Lawn, Erzsébet Horváth-Puhó
Journal: Journal of Infection (2025)

The long-term risk of child and adolescent psychiatric disorders (PDs) after neonatal invasive group B Streptococcus disease (iGBS) and the modifying factors are poorly understood. A population-based matched cohort study, including 1,548 infants with iGBS diagnosed during the first 3 months of life from 1997 through 2020 and follow-up until 2022, based on data from Danish national health and administrative registers. A general population comparison cohort of infants without iGBS was randomly sampled and matched 1:10 by sex, the child's birth year and month, and gestational age (n= 15,345). The cumulative incidence proportion (CIP) with 95% confidence intervals (CIs) of any PD was 21.1% (95% CI 18.7-23.7) in infants exposed to iGBS (88% sepsis, 12% meningitis) and 16.2% (95% CI 15.5-17.0) in the comparison cohort. The 18-year CIP of PD was higher for infants exposed to iGBS meningitis compared to iGBS sepsis. The adjusted hazard ratio for PD in infants with iGBS was 1.41 (95% CI 1.23-1.62). iGBS in early infancy is a risk factor for PDs, especially iGBS meningitis. Premature birth, gestational diabetes, and low maternal education increased the risk of any PD further. Group B Streptococcus (Streptococcus Agalactiae) remains the leading cause of neonatal, invasive disease and is associated with high mortality and risk of neurodevelopmental impairments. Scarce data exist regarding the long-term risk of psychiatric disorders following invasive group B Streptococcus disease in early infancy (iGBS), especially following sepsis. In this Danish national cohort study, we investigated the association of iGBS and the risk of psychiatric disorders until adolescence and early adulthood. We investigated to which extend premature birth, sex (at birth), maternal socioeconomic position or gestational diabetes were modifying the association between iGBS and psychiatric disorders. Our study found an increased risk of psychiatric disorders persisting into adolescence following iGBS, including both meningitis and sepsis. Specific psychiatric disorders with elevated risk included anxiety, obsessive compulsive disorder, autism, and attention deficit hyperactivity disorder. Premature birth, maternal gestational diabetes, and low maternal education further increased the risk of any psychiatric disorders, whereas the child's sex did not.