tbuckley/cabot-search huggingface dataset:
Microbiome-Centered Therapies for the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease
Authors: Huma Saeed, Luis Antonio Díaz, Antonio Gil-Gómez, Jeremy Burton, Jasmohan Bajaj, Manuel Romero-Gomez, Marco Arrese, Juan Pablo Arab, Mohammad Qasim Khan
Journal: Clinical and Molecular Hepatology (2024)

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a significant global health issue, affecting over 30% of the population worldwide due to the rising prevalence of metabolic risk factors such as obesity and type 2 diabetes mellitus (T2DM). This spectrum of liver disease ranges from isolated steatosis to more severe forms such as steatohepatitis, fibrosis, and cirrhosis. Recent studies highlight the role of gut microbiota in MASLD pathogenesis, showing that dysbiosis significantly impacts metabolic health and the progression of liver disease. This review critically evaluates current microbiome-centered therapies in MASLD management, including prebiotics, probiotics, synbiotics, fecal microbiota transplantation (FMT), and emerging therapies such as engineered bacteria and bacteriophage therapy. We explore the scientific rationale, clinical evidence, and potential mechanisms by which these interventions influence MASLD. The gut-liver axis is crucial in MASLD, with notable changes in microbiome composition linked to disease progression. For instance, specific microbial profiles and reduced alpha diversity are associated with MASLD severity. Therapeutic strategies targeting the microbiome could modulate disease progression by improving gut permeability, reducing endotoxin-producing bacteria, and altering bile acid metabolism. Although promising, these therapies require further research to fully understand their mechanisms and optimize their efficacy. This review integrates findings from clinical trials and experimental studies, providing a comprehensive overview of microbiome-centered therapies' potential in managing MASLD. Future research should focus on personalized strategies, utilizing microbiome features, blood metabolites, and customized dietary interventions to enhance the effectiveness of these therapies.
Efficacy of pH‐Responsive Surface Functionalized Titanium Screws in Treating Implant‐associated <i>S. aureus</i> Osteomyelitis with Biofilms Formation
Authors: Hang Zhou, Youliang Ren, Kaixiong Zou, Ying Jin, Hang Liu, Haitao Jiang, Lei Shi, Xiaomin Sheng, Jason Weeks, Hannah Wang, Thomas Xue, Edward M. Schwarz, Chao Xie, Zhongliang Deng, Lin Wang, Lei Chu
Journal: Advanced Healthcare Materials (2024)

Abstract Implant‐associated Staphylococcus aureus (S. aureus) osteomyelitis (IASO) leads to high orthopedic implant failure rates due to the formation of Staphylococcal abscess community within the bone marrow and bacterial colonization in the osteocyte lacuno‐canalicular network (OLCN). To address this, antimicrobial peptides (HHC36)‐loaded titania nanotubes (NTs) are developed on titanium screws (Ti‐NTs‐P‐A), which integrate pH‐responsive polymethacrylic acid to control HHC36 release for eradicating bacteria in IASO. Colony‐forming unit assay confirmed that Ti‐NTs‐P‐A screws maintained sustainable antibacterial effectiveness, killing over 65% of S. aureus even after multiple bacterial solution replacements. Notably, Ti‐NTs‐P‐A screws exhibit significant pH‐responsive HHC36 release behavior and bactericidal activity, consistent with the phenotype of peptides‐killed bacteria from scanning electron microscopy. Transcriptome sequencing results reveal that Ti‐NTs‐P‐A screws interfered with ribosome formation and disrupted the arginine biosynthesis, which is crucial for bacterial survival in acidic environments. In the non‐infected implant model, the bone‐implant contact ratio of the Ti‐NTs‐P‐A screw is 2.3 times that of the clinically used titanium screw. In an IASO model, Ti‐NTs‐P‐A screws effectively eradicated bacteria within the OLCN, achieving an 80% infection control rate and desirable osteointegration. Collectively, Ti‐NTs‐P‐A screws with pH‐responsive antibacterial properties exhibit great potential for eradicating bacteria and achieving osseointegration in IASO.
Multifunctional Adhesive Hydrogels: From Design to Biomedical Applications
Authors: Shaoxin Tang, Keru Feng, Rui Yang, Yang Cheng, Meiyue Chen, Hui Zhang, Nianyuan Shi, Zhao Wei, Hui Ren, Yufei Ma
Journal: Advanced Healthcare Materials (2024)

Abstract Adhesive hydrogels characterized by structural properties similar to the extracellular matrix, excellent biocompatibility, controlled degradation, and tunable mechanical properties have demonstrated significant potential in biomedical applications, including tissue engineering, biosensors, and drug delivery systems. These hydrogels exhibit remarkable adhesion to target substrates and can be rationally engineered to meet specific requirements. In recent decades, adhesive hydrogels have experienced significant advancements driven by the introduction of numerous multifunctional design strategies. This review initially summarizes the chemical bond‐based design strategies for tissue adhesion, encompassing static covalent bonds, dynamic covalent bonds, and non‐covalent interactions. Subsequently, the multiple functionalities imparted by these diverse design strategies, including highly stretchable and tough performances, responsiveness to microenvironments, anti‐freezing/heating properties, conductivity, antibacterial activity, and hemostatic properties are discussed. In addition, recent advances in the biomedical applications of adhesive hydrogels, focusing on tissue repair, drug delivery, medical devices, and wearable sensors are reviewed. Finally, the current challenges are highlighted and future trends in this rapidly evolving field are discussed.
β<sub>3</sub>‐Adrenoceptor Agonism to Mimic the Biological Effects of Intrauterine Hypoxia: Taking Great Strides Toward a Pharmacological Artificial Placenta
Authors: Luca Filippi, Francesca Innocenti, Francesca Pascarella, Rosa Teresa Scaramuzzo, Riccardo Morganti, Paola Bagnoli, Maurizio Cammalleri, Massimo Dal Monte, Maura Calvani, Alessandro Pini
Journal: Medicinal Research Reviews (2024)

ABSTRACT At different stages of life, from embryonic to postnatal, varying oxygen concentrations modulate cellular gene expression by enhancing or repressing hypoxia‐inducible transcription factors. During embryonic/fetal life, these genes encode proteins involved in adapting to a low‐oxygen environment, including the induction of specific enzymes related to glycolytic metabolism, erythropoiesis, angiogenesis, and vasculogenesis. However, oxygen concentrations fluctuate during intrauterine life, enabling the induction of tissue‐specific differentiation processes. Fetal well‐being is thus closely linked to the physiological benefits of a dynamically hypoxic environment. Premature birth entails the precocious exposure of the immature fetus to a more oxygen‐rich environment compared to the womb. As a result, preterm newborns face a condition of relative hyperoxia, which alters the postnatal development of organs and contributes to prematurity‐related diseases. However, until recently, the molecular mechanism by which high oxygen tension alters normal fetal differentiation remained unclear. In this review, we discuss the research trajectory followed by our research group, which suggests that early exposure to a relatively hyperoxic environment may impair preterm neonates due to reduced expression of the β 3 ‐adrenoceptor. Additionally, we explore how these impairments could be prevented through the pharmacological stimulation of the remaining β3‐adrenoceptors. Recent preclinical studies demonstrate that pharmacological stimulation of the β 3 ‐adrenoceptor can decouple exposure to hyperoxia from its harmful effects, offering a glimpse of the possibility to recreating the conditions typical of intrauterine life, even after premature birth.
Advancing health and fostering community involvement in medical research through the Genes &amp; Health study
Authors: Marie Spreckley, Mehru Raza, Kamrul Islam, Jessry Russell, Karen Hunt, Ceri Durham, None Genes Health Research Team, David van Heel, Ahsan Khan, Sarah Finer, Moneeza K Siddiqui
Journal: Trends in Endocrinology and Metabolism (2024)
CD-19 CAR-T cells for polyrefractory rheumatoid arthritis
Authors: Merav Lidar, Doron Rimar, Paula David, Elad Jacoby, Ronnie Shapira-Frommer, Orit Itzhaki, Gleb Slobodin, Myriam D Stern, Iris Eshed, Tamer Sanalla, Ronit Marcus, Avichai Shimoni, Ronit Yerushalmi, Noga Shem Tov, Ivetta Danylesko, Abraham Avigdor
Journal: Annals of the Rheumatic Diseases (2025)
Contemporary menopausal hormone therapy and risk of cardiovascular disease: Swedish nationwide register based emulated target trial
Authors: Therese Johansson, Torgny Karlsson, Dana Bliuc, Daniel Schmitz, Weronica E Ek, Alkistis Skalkidou, Jacqueline R Center, Åsa Johansson
Journal: BMJ (2024)

To assess the effect of contemporary menopausal hormone therapy on the risk of cardiovascular disease according to the route of administration and combination of hormones.
Ivarmacitinib, a selective Janus kinase 1 inhibitor, in patients with moderate-to-severe active rheumatoid arthritis and inadequate response to conventional synthetic DMARDs: results from a phase III randomised clinical trial
Authors: Jinjing Liu, Ying Jiang, Shangzhu Zhang, Shengyun Liu, Jingbo Su, Changsong Lin, Xiaohong He, Rui Wu, Lei Yang, Huaxiang Liu, Xinwang Duan, Shengqian Xu, Hui Luo, Jing Liu, Qibing Xie, Cundong Mi, Lin Chen, Ning Zhang, Huiping Gong, Jing Zhu, Yasong Li, Hua Wei, Long Qian, Jian Wang, Xiaofei Shi, Hongtao Jin, Zhenyu Jiang, Xi Xie, Feng Zhan, Xiuqin Geng, Zhaohui Zheng, Zhengfu Du, Guangchao Dong, Yuqi Sun, Xiaofeng Zeng
Journal: Annals of the Rheumatic Diseases (2025)

To assess the efficacy/safety of ivarmacitinib, a selective Janus kinase (JAK) 1 inhibitor, in patients with moderate-to-severe active rheumatoid arthritis (RA) who had an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Patients were randomised (1:1:1) to receive either placebo (n=188), ivarmacitinib 4 mg (n=189) or ivarmacitinib 8 mg (n=189) once daily, with background csDMARDs allowed. After 24 weeks, patients on placebo switched to ivarmacitinib 4 mg for an additional 28 weeks, while those on ivarmacitinib continued their initial dosage. The primary endpoint was the proportion of patients achieving a 20% improvement in the American College of Rheumatology response criteria (ACR20) at week 24. At week 24, ACR20 response rates were significantly higher in the ivarmacitinib 4 mg (70.4%) and 8 mg (75.1%) groups compared with the placebo group (40.4%; both p<0.0001). Both ivarmacitinib doses achieved numerically higher Disease Activity Score 28-joint count C reactive protein of <2.6/≤3.2 response rates compared with placebo. Improvements in efficacy and patient-reported outcomes were sustained through 52 weeks and were noted in patients who switched from placebo after week 24. During the placebo-controlled period, treatment-emergent adverse events (TEAEs) occurred in 81.5% and 90.5% of patients in the ivarmacitinib 4 mg and 8 mg groups, versus 79.3% in the placebo group. Infection-related TEAEs were slightly higher in the ivarmacitinib groups. Ivarmacitinib may offer a potential therapeutic option for patients with RA who have an inadequate response to csDMARDs, with a safety profile that was generally manageable over 1 year of treatment and similar to other JAK inhibitors. NCT04333771.
Diabetes Body Project: Acute Effects of an Eating Disorder Prevention Program for Young Women With Type 1 Diabetes. A Multinational Randomized Controlled Trial
Authors: Mareille H.C.L. Hennekes, Severina Haugvik, Maartje de Wit, Elena Toschi, Christopher D. Desjardins, Torild Skrivarhaug, Knut Dahl-Jørgensen, Eric Stice, Line Wisting
Journal: Diabetes Care (2024)

Young women with type 1 diabetes are at risk to develop eating disorders (ED). We evaluated a novel ED prevention program in a multinational randomized controlled trial.
White paper: Understanding, informing and defining the regulatory science of microneedle-based dosage forms that are applied to the skin
Authors: Maria Dul, Mohammed Alali, Mahmoud Ameri, Matthew Douglas Burke, Benjamin Paul Creelman, Lisa Dick, Ryan F Donnelly, Michael N Eakins, Collrane Frivold, Angus Harry Forster, Philippe-Alexandre Gilbert, Stefan Henke, Sebastien Henry, Desmond Hunt, Hayley Lewis, Jessica Joyce Mistilis, Jung-Hwan Park, Mark R Prausnitz, David Kenneth Robinson, Carmen Amelia Rodriguez Hernandez, Juyeop Shin, Tycho Joseph Speaker, Caroline Strasinger, Kevin M G Taylor, Darin Zehrung, James C Birchall, Courtney Jarrahian, Sion A Coulman
Journal: Journal of Controlled Release (2024)

The COVID-19 pandemic has accelerated pre-clinical and clinical development of microneedle-based drug delivery technology. However the regulatory science of this emerging dosage form is immature and explicit regulatory guidance is limited. A group of international stakeholders has formed to identify and address key issues for the regulatory science of future products that combine a microneedle device and active pharmaceutical ingredient (in solid or semi-solid state) in a single entity that is designed for application to the skin. Guided by the principles of Quality by Design (QbD) and informed by consultation with wider stakeholders, this 'White Paper' describes fundamental elements of the work in an effort to harmonise understanding, stimulate discussion and guide innovation. The paper discusses classification of the dosage form (combination/medicinal product), the regulatory nomenclature that is likely to be adopted and the technical vocabulary that best describes its form and function. More than twenty potential critical quality attributes (CQAs) are identified for the dosage form, and a prioritisation exercise identifies those CQAs that are most pertinent to the dosage form and that will likely require bespoke test methods (delivered dose, puncture performance) or major adaptions to established compendial test methods (dissolution). Hopefully the work will provide a platform for the development of dosage form specific guidance (from regulatory authorities and/or international pharmacopoeias), that expedites clinical translation of safe and effective microneedle-based products.
Extracellular vesicles in cancers: mechanisms, biomarkers, and therapeutic strategies
Authors: Yuxi Ma, Xiaohui Zhang, Cuiwei Liu, Yanxia Zhao
Journal: MedComm (2024)

Abstract Extracellular vesicles (EVs) composed of various biologically active constituents, such as proteins, nucleic acids, lipids, and metabolites, have emerged as a noteworthy mode of intercellular communication. There are several categories of EVs, including exosomes, microvesicles, and apoptotic bodies, which largely differ in their mechanisms of formation and secretion. The amount of evidence indicated that changes in the EV quantity and composition play a role in multiple aspects of cancer development, such as the transfer of oncogenic signals, angiogenesis, metabolism remodeling, and immunosuppressive effects. As EV isolation technology and characteristics recognition improve, EVs are becoming more commonly used in the early diagnosis and evaluation of treatment effectiveness for cancers. Actually, EVs have sparked clinical interest in their potential use as delivery vehicles or vaccines for innovative antitumor techniques. This review will focus on the function of biological molecules contained in EVs linked to cancer progression and their participation in the intricate interrelationship within the tumor microenvironment. Furthermore, the potential efficacy of an EV‐based liquid biopsy and delivery cargo for treatment will be explored. Finally, we explicitly delineate the limitations of EV‐based anticancer therapies and provide an overview of the clinical trials aimed at improving EV development.
A call to innovate Antarctic avian influenza surveillance
Authors: Michelle Wille, Meagan L Dewar, Filip Claes, Peter Thielen, Erik A Karlsson
Journal: Trends in Ecology & Evolution (2024)

Highly pathogenic avian influenza (HPAI) viruses are increasingly spreading between birds and mammals globally, with sporadic transmission to humans. With recent emergence in Antarctica, traditional animal capture and influenza testing approaches have proven challenging and logistically impractical. Without reference laboratories in the region, responses are slow and few samples will ever be collected or tested from local outbreaks due to lack of infrastructure. We call for development of innovative data collection strategies that can be deployed for a diverse range of sample types for rapid, field-forward characterization. Policy shifts and enhanced biosecurity protocols are required to protect Antarctic biodiversity, and we advocate for global coordination and strengthened collaborations between national programs, tour operators, and scientists to establish a 'smart surveillance' network.
How might the provision of smoking cessation services be adapted to improve uptake and success for people in low socioeconomic groups? A qualitative study (PROCESS Study)
Authors: Pamela Smith, Lucia Dahlby, Evgeniya Plotnikova, Rebecca-Bell Williams, Rebecca Thorley, Fiona Dobbie, Tessa Langley, Ilze Bogdanovica, Kate Brain, Rachael Murray, Leah Jayes
Journal: The Lancet (2024)
The quantitative evaluation of the impact of a new outdoor advertising restrictions policy in Bristol: a natural experiment evaluation.
Authors: Genevieve Buckland, Zoi Toumpakari, Russell Jago, Sarah Harding, James Nobles, Jeremy Horwood, Carlos Sillero Rejon, William Hollingworth, Steve Cummins, Sarah Blake, Agnes Nairn, Frank de Vocht
Journal: The Lancet (2024)
Mixed-methods evaluation of a co-designed peer-led intervention to tackle barriers to early diagnosis of prostate cancer for Black men in North-East England and Scotland
Authors: Floor Christie-de Jong, Olugbenga Samuel Oyeniyi, Judith Eberhardt, John Kabuye, Martin Kalemba, Lawrence Nnyanzi, Marie Kotzur, Kathryn A Robb
Journal: The Lancet (2024)
Generative AI: ensuring transparency and emphasising human intelligence and accountability
Authors: Jessamy Bagenal, Christina Biamis, Morgane Boillot, Rob Brierley, Mabel Chew, Tim Dehnel, Helen Frankish, Emma Grainger, Jessica Pope, Jamie Prowse, Diana Samuel, Amy L Slogrove, Julie Stacey, Gita Thapaliya, Fio Trethewey, Helena Hui Wang, Joshua Varley-Reeves, Sabine Kleinert
Journal: The Lancet (2024)
Qualitative evaluation of the new outdoor advertising restrictions policy in Bristol: stakeholder perspectives on the policy implementation
Authors: Sarah Harding, James Nobles, Jeremy Horwood, Genevieve Buckland, Zoi Toumpakari, Russ Jago, William Hollingworth, Steve Cummins, Agnes Nairn, Carlos Sillero Rejon, Sarah Blake, Frank de Vocht
Journal: The Lancet (2024)
The role of primary care in hepatitis B elimination in the UK migrant context, a mixed-methods study
Authors: Jessica Carter, Kenneth Kabagambe, Joy Ko, Stuart Flanagan, Indrajit Ghosh, Kathryn Jack, Farah Seedat, Ahmed Elsharkawy, Philippa Harris, Binta Sultan, David Moore, Michael Brown, Philippa Matthews, Sally Hargreaves
Journal: The Lancet (2024)
How has local authority expenditure on public health services for 0 to 5-year-olds in England changed over time? An analysis of national administrative data from 2016/17 to 2022/23
Authors: Louise McGrath-Lone, Anjali Raman Middleton, Amanda Clery, Catherine Bunting, Eirini-Christina Saloniki, Jenny Woodman, Katie Harron
Journal: The Lancet (2024)
Increasing uptake of Live Attenuated Influenza Vaccination (LAIV) in two-year-olds through appointment times and dates: A pilot intervention in Cwm Taf Morgannwg University Health Board
Authors: Megan Elliott, Charlotte Todd, Caroline Harris, Rhian Meaden, Rhianydd Davey, Mark Gall, Hayley Gale, Hawys Youlden, Rosemary Jones, Simon Cottrell
Journal: The Lancet (2024)
National reporting on factors associated with health inequalities and infection, antimicrobial resistance and consumption rates in England: 2018–2022
Authors: Ellie L Gilham, Hannah Higgins, Emily Mason, Katherine L Henderson, Mariyam Mirfenderesky, Sabine Bou-Antoun, Alicia Demirjian, Russell Hope, Colin Brown, Diane Ashiru-Oredope
Journal: The Lancet (2024)
Treating eosinophilic exacerbations of asthma and COPD with benralizumab (ABRA): a double-blind, double-dummy, active placebo-controlled randomised trial
Authors: Sanjay Ramakrishnan, Richard E K Russell, Hafiz R Mahmood, Karolina Krassowska, James Melhorn, Christine Mwasuku, Ian D Pavord, Laura Bermejo-Sanchez, Imran Howell, Mahdi Mahdi, Stefan Peterson, Thomas Bengtsson, Mona Bafadhel
Journal: The Lancet Respiratory Medicine (2024)
Safety and efficacy of intravenous recombinant human prourokinase for acute ischaemic stroke within 4·5 h after stroke onset (PROST-2): a phase 3, open-label, non-inferiority, randomised controlled trial
Authors: Shuya Li, Hong-Qiu Gu, Baoyu Feng, Hao Li, Xuechun Wang, Qiang Dong, Dongsheng Fan, Yun Xu, Suiqiang Zhu, Hongguo Dai, Yan Wei, Ziran Wang, Guozhi Lu, Yutong Ma, Zixiao Li, Yilong Wang, Xia Meng, Xingquan Zhao, Liping Liu, Yongjun Wang
Journal: The Lancet Neurology (2024)
Global, regional, and national mortality burden attributable to air pollution from landscape fires: a health impact assessment study
Authors: Rongbin Xu, Tingting Ye, Wenzhong Huang, Xu Yue, Lidia Morawska, Michael J Abramson, Gongbo Chen, Pei Yu, Yanming Liu, Zhengyu Yang, Yiwen Zhang, Yao Wu, Wenhua Yu, Bo Wen, Yuxi Zhang, Simon Hales, Eric Lavigne, Paulo H N Saldiva, Micheline S Z S Coelho, Patricia Matus, Dominic Roye, Jochem Klompmaker, Malcolm Mistry, Susanne Breitner, Ariana Zeka, Raanan Raz, Shilu Tong, Fay H Johnston, Joel Schwartz, Antonio Gasparrini, Yuming Guo, Shanshan Li
Journal: The Lancet (2024)