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{"title":"The role of wild birds in pathogen dynamics: Ecological hotspots, surveillance strategies, and global health implications.","authors":"Mohamed A Bakheet, Justin Bahl","doi":"10.1016/j.medj.2025.100606","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100606","url":null,"abstract":"<p><p>Wild birds spread pathogens that threaten animals and humans, acting as reservoirs and vectors. Qiu et al.¹ analyzed 1,834 studies, identifying 760 pathogens in 1,438 bird species, including zoonotic and emerging threats. Their research highlights global hotspots, showing that migratory birds aid dispersal while resident birds drive local transmission, emphasizing the need for enhanced surveillance to mitigate zoonotic and pandemic risks.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 4","pages":"100606"},"PeriodicalIF":12.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AAV gene therapy for mucopolysaccharidoses.","authors":"Shaukat Khan, Yasuhiko Ago, Shunji Tomatsu","doi":"10.1016/j.medj.2025.100609","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100609","url":null,"abstract":"<p><p>Adeno-associated viral (AAV) vectors emerge as a promising treatment option for genetic diseases. They are recognized as the most effective in vivo gene therapy due to their safety, efficacy, and ability to provide long-term therapeutic transgene expression.¹^,²^,³ Rossi et al.¹ have demonstrated that AAV gene therapy is effective and safe for treating patients with mucopolysaccharidosis VI, paving the way for potential treatments for mucopolysaccharidoses.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 4","pages":"100609"},"PeriodicalIF":12.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144031359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UV1 vaccination in pembrolizumab-treated patients with recurrent or metastatic head and neck cancer: A randomized multicenter phase 2 trial.","authors":"Anna Brandt, Konrad Klinghammer, Christoph Schultheiss, Lisa Paschold, Claudia Wickenhauser, Marcus Bauer, Anna Bergqvist, Dennis Hahn, Philippe Schafhausen, Mareike Tometten, Markus Blaurock, Henrike Barbara Zech, Chia-Jung Busch, Andreas Dietz, Urs Müller-Richter, Jürgen Alt, Andreas Boehm, Simone Kowoll, Jörg Steighardt, Alexander Lasch, Ingunn Hagen Westgaard, Marita Westhrin, Alexander Stein, Axel Hinke, Mascha Binder","doi":"10.1016/j.medj.2025.100647","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100647","url":null,"abstract":"<p><strong>Background: </strong>Human telomerase reverse transcriptase is highly expressed in head and neck squamous cell carcinoma (HNSCC). The FOCUS study examines the role of the telomerase-directed vaccine UV1 in combination with pembrolizumab in patients with recurrent or metastatic (R/M) HNSCC.</p><p><strong>Methods: </strong>The FOCUS trial, a two-armed, open-label, randomized, multicenter phase 2 study, was designed to assess the efficacy and feasibility of UV1 as an add-on to pembrolizumab in the first-line treatment of patients with R/M PD-L1⁺ HNSCC. A progression-free survival (PFS) rate at 6 months of 40% was deemed promising for further development in a phase 3 setting. The trial was conducted in 10 centers in Germany (this study was registered at ClinicalTrials.gov: NCT05075122).</p><p><strong>Findings: </strong>From August 2021 to July 2023, 25 patients were enrolled in the pembrolizumab arm and 50 patients in the pembrolizumab + UV1 arm. The PFS rate at 6 months was 40% in the pembrolizumab arm and 30% in the pembrolizumab + UV1 arm. No specific safety signals were observed in the pembrolizumab + UV1 arm apart from a reversible allergic reaction that appeared in one patient. At a median follow-up of 11.3 months, median overall survival was 13.1 months in the pembrolizumab arm and 12.6 months in the pembrolizumab + UV1 arm.</p><p><strong>Conclusions: </strong>The addition of UV1 to pembrolizumab was safe but did not show an efficacy signal in this study population.</p><p><strong>Funding: </strong>The legal sponsor of the trial was the University Medical Center Halle (Saale), Germany and was funded by a grant from Ultimovacs.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100647"},"PeriodicalIF":12.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144031625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"No association between the early-life gut microbiota and childhood body mass index and body composition.","authors":"Christina Egeø Poulsen, Rebecca Vinding, Morten A Rasmussen, Shiraz Shah, Urvish Trivedi, Cristina Leal Rodriguez, Michael L Widdowson, Jie Jiang, Casper S Poulsen, Anders Eliasen, Bo Chawes, Klaus Bønnelykke, Camilla H F Hansen, Søren J Sørensen, Jonathan Thorsen, Jakob Stokholm","doi":"10.1016/j.medj.2024.10.015","DOIUrl":"10.1016/j.medj.2024.10.015","url":null,"abstract":"<p><strong>Background: </strong>The gut microbiota has been implicated in adult obesity, but the causality is still unclear. It has been hypothesized that an obesity-prone gut microbiota can be established in infancy, but only few studies have examined the early-life gut microbiota in relation to obesity in childhood, and no consistent associations have been reported. Here, we examine the association between the early-life gut microbiota and body mass index (BMI) development and body composition throughout childhood.</p><p><strong>Methods: </strong>Gut microbiota from stool were collected from 700 children in the Copenhagen Prospective Studies on Asthma in Childhood₂₀₁₀ (COPSAC₂₀₁₀) cohort at ages of 1 week, 1month, 1 year, 4 years, and 6 years and analyzed by 16S rRNA gene sequencing. Outcomes included BMI World Health Organization (WHO) Z scores (zBMI), overweight (zBMI > 1.04) and obesity (zBMI > 1.64) (0-10 years), and adiposity rebound and body composition from dual-energy X-ray absorptiometry at 6 years.</p><p><strong>Findings: </strong>The early-life gut microbiota diversity, overall composition, and individual taxon abundances in unsupervised and supervised models were not consistently associated with either current or later BMI Z scores, overweight, obesity, adiposity rebound, or body composition in childhood.</p><p><strong>Conclusions: </strong>In a deeply characterized longitudinal birth cohort, we did not observe any consistent associations between the early-life gut microbiota and BMI or risk of obesity in later childhood. While this does not conclusively rule out a relationship, it suggests that if such associations exist, they may be more complex and potentially influenced by factors emerging later in life, including lifestyle changes.</p><p><strong>Funding: </strong>COPSAC is funded by private and public research funds (all listed on www.copsac.com).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100538"},"PeriodicalIF":12.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hb Monza: A novel extensive HBB duplication with preserved α-β subunit interaction and unstable hemoglobin phenotype.","authors":"Ivan Civettini, Arianna Zappaterra, Paola Corti, Amedeo Messina, Andrea Aroldi, Andrea Biondi, Fabrizio Cavalca, Valentina Crippa, Francesca Crosti, Giulia Maria Ferrari, Federica Malighetti, Luca Mologni, Alberto Piperno, Daniele Ramazzotti, Chiara Scollo, Alfonso Zambon, Fabio Rossi, Carlo Gambacorti-Passerini","doi":"10.1016/j.medj.2024.11.007","DOIUrl":"10.1016/j.medj.2024.11.007","url":null,"abstract":"<p><strong>Background: </strong>Unstable hemoglobins are caused by single amino acid substitutions in the HBB gene, often affecting key histidine residues, leading to protein destabilization and hemolytic crises. In contrast, long HBB variants, exceeding 20 bp, are rare and associated with a β-thalassemia phenotype due to disrupted α-β chain interactions. We describe a family wherein four of six members carry a novel 23-amino-acid in-frame duplication of HBB (c.176_244dup), named hemoglobin (Hb) Monza. Despite its length, this duplication manifests as an unstable hemoglobin variant rather than a β-thalassemia phenotype.</p><p><strong>Methods: </strong>A static 3D model of the Hb Monza β chain was generated using AlphaFold and SWISS-MODEL. Molecular dynamics (MD) simulations were performed with the Generalized Born implicit solvent model. After energy minimization and heating to 311 K (38°C), a 40 ns production run was conducted.</p><p><strong>Findings: </strong>3D modeling of Hb Monza revealed minimal structural changes in the Hb β chain, particularly in the key histidine residues and their interaction with the iron atom. Additionally, the static 3D model showed a preserved α-β interaction, explaining the absence of a β-thalassemia clinical phenotype. MD simulations under thermal stress revealed a notable increase in root-mean-square deviation compared to the wild-type β subunit, along with a loss of contacts with the heme, explaining the hemolytic crises during febrile episodes.</p><p><strong>Conclusion: </strong>Despite the long duplication in HBB, Hb Monza retains functional α-β interaction while demonstrating instability under stressful conditions. This unique variant presents with an unstable Hb phenotype rather than a β-thalassemia phenotype.</p><p><strong>Funding: </strong>No financial funding was received.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100554"},"PeriodicalIF":12.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The global distribution and diversity of wild-bird-associated pathogens: An integrated data analysis and modeling study.","authors":"Yunbo Qiu, Chenlong Lv, Jinjin Chen, Yanqun Sun, Tian Tang, Yuanyuan Zhang, Yufeng Yang, Guolin Wang, Qiang Xu, Xiaoai Zhang, Feng Hong, Simon I Hay, Liqun Fang, Wei Liu","doi":"10.1016/j.medj.2024.11.006","DOIUrl":"10.1016/j.medj.2024.11.006","url":null,"abstract":"<p><strong>Background: </strong>Wild birds are significant vectors in global pathogen transmission, but the diversity and spatial distribution of the pathogens detected in them remain unclear. Understanding the transmission dynamics and hotspots of wild-bird-associated pathogens (WBAPs) is crucial for early disease prevention.</p><p><strong>Methods: </strong>We compiled an up-to-date dataset encompassing all WBAPs by conducting an extensive search of publications from 1959 to 2022, mapped their diversity and global distribution, and utilized three machine learning algorithms to predict geospatial hotspots where zoonotic and emerging WBAPs were prevalent.</p><p><strong>Findings: </strong>Based on 1,834 selected studies, a total of 760 pathogens associated with 1,438 wild bird species were identified, including 387 emerging and 212 zoonotic pathogens. Migratory birds exhibited higher pathogen richness (593 species) but a lower proportion of zoonotic pathogens (27.2%) compared to resident birds (303 species and 39.3%, both p < 0.01). When comparing different ecological groups, waterfowl had the highest richness of zoonotic pathogens (128 species), followed by songbirds (76 species). The distribution of WBAPs was significantly influenced by the habitat suitability index of wild birds, mammalian richness, and climatic factors. The potential geographical hotspots of zoonotic and emerging WBAPs were widely distributed in tropical areas of Asia, Africa, and South America, with zoonotic WBAPs having a wider distribution in South America.</p><p><strong>Conclusions: </strong>Our study illustrates that the geographical hotspots of WBAPs are more widespread than reported, especially in low-income areas, and that the identification, surveillance, and prevention of WBAP infections should be prioritized.</p><p><strong>Funding: </strong>This work was funded by the National Key Research and Development Program of China.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100553"},"PeriodicalIF":12.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"eNRGy: Making progress toward a future for NRG1 fusion-positive cancer.","authors":"Lucia Anna Muscarella, Massimo Di Maio","doi":"10.1016/j.medj.2025.100641","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100641","url":null,"abstract":"<p><p>The eNRGy trial demonstrated zenocutuzumab's efficacy in advanced cancer with NRG1 fusion, mainly non-small cell lung and pancreatic cancers.¹ Responses were observed across multiple tumor types identified through RNA-based next-generation sequencing, with low-grade adverse events. This suggests a potentially agnostic role of NRG1 fusions in solid tumors and underscores the need for comprehensive gene fusion testing in patients with cancer.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 4","pages":"100641"},"PeriodicalIF":12.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging the gaps: Overcoming challenges of implementing AI in healthcare.","authors":"Xiaoyun Huang, Lei Gu, Jian Sun, Roland Eils","doi":"10.1016/j.medj.2025.100666","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100666","url":null,"abstract":"<p><p>Artificial intelligence (AI) in healthcare promises transformative advancements, from enhancing diagnostics to optimizing personalized treatments. Realizing its full potential, however, requires addressing key challenges, including explainability, bias & fairness, infrastructure, privacy, security, as well as ethical, regulatory and educational challenges. Bridging these gaps is essential to ensure AI's equitable and effective integration into clinical practice.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 4","pages":"100666"},"PeriodicalIF":12.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AMPLIFY: A second-generation BTK inhibitor for fixed-duration therapy in chronic lymphocytic leukemia.","authors":"Stefano Molica","doi":"10.1016/j.medj.2025.100665","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100665","url":null,"abstract":"<p><p>Recent advancements in chronic lymphocytic leukemia (CLL) treatment emphasize fixed-duration (FD) strategies, notably venetoclax with obinutuzumab or ibrutinib, now endorsed by ESMO guidelines. The AMPLIFY phase 3 trial highlights acalabrutinib-venetoclax combinations, demonstrating superior progression-free survival and manageable safety.¹ These findings support FD regimens as a paradigm shift, optimizing efficacy, safety, and patient convenience in frontline CLL therapy.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 4","pages":"100665"},"PeriodicalIF":12.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144049853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"B cell depletion in lupus nephritis: From disappointments to hopes, despite some concerns.","authors":"Antoine Enfrein, Frédéric A Houssiau","doi":"10.1016/j.medj.2025.100640","DOIUrl":"https://doi.org/10.1016/j.medj.2025.100640","url":null,"abstract":"<p><p>Lupus nephritis is the most common severe manifestation of systemic lupus erythematosus. B cells are key drivers of the disease as they produce autoantibodies that deposit in the kidneys, triggering inflammatory response and damage. The REGENCY trial¹ demonstrates that addition of the anti-CD20 monoclonal antibody obinutuzumab on top of standard-of-care significantly improves complete renal remission rate.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 4","pages":"100640"},"PeriodicalIF":12.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}