tbuckley/cabot-search huggingface dataset:
Impact of routine prophylaxis with monoclonal antibodies and maternal immunisation to prevent respiratory syncytial virus hospitalisations, Lombardy region, Italy, 2024/25 season
Authors: Francesco Menegale, Luigi Vezzosi, Marcello Tirani, Simona Scarioni, Stefano Odelli, Federica Morani, Catia Borriello, Elena Pariani, Ilaria Dorigatti, Danilo Cereda, Stefano Merler, Piero Poletti
Journal: Eurosurveillance (2025)

Background Respiratory syncytial virus (RSV) is a leading cause of hospitalisation in children worldwide. Recent regulatory approval of monoclonal antibody (mAb) nirsevimab for infants and the RSVpreF vaccine for pregnant women offers promising approaches to mitigate RSV-associated morbidity. Aim To evaluate potential impacts of routine prophylactic campaigns (mAbs targeting infants or maternal vaccination) introduced in the 2024/25 season on hospitalisations from RSV lower respiratory tract infections in Lombardy, Italy. Methods We used a catalytic model informed by data from pre-COVID-19 pandemic (before 2020) and post-pandemic periods (until 2022) to quantify the number of cases and hospitalisations that could be averted by seasonal nirsevimab administration to infants and RSVpreF maternal vaccination, considering changes in susceptibility caused by reduced RSV circulation during the pandemic. Results As a marked proportion of RSV hospitalisations occurs in infants aged ≤ 1 year, seasonal mAb administration to 80% of newborns (uptake levels observed in Spain) was estimated to avert 50.2% (95% CI: 43.5–55.8) of hospitalisations in the total population. Coverage levels close to those observed for childhood vaccines (95%) could result in an additional average 18% reduction in hospitalisations. Vaccination of 65% of pregnant women, resembling the diphtheria–tetanus–pertussis vaccine coverage in Lombardy for this population, was estimated to avert 30.5% (95% CI: 19.6–39.7) of hospitalisations. At influenza vaccine coverage (12%), less than 8% of hospitalisations could be averted by maternal immunisation. Conclusion Routine nirsevimab administration to infants demonstrates clear potential to reduce RSV-associated hospitalisations. Maternal immunisation can help in achieving high protection in at-risk populations.
Epidemiological characteristics and trends of notified enteric fevers in Germany, 2001 to 2023
Authors: Julia Enkelmann, Sandra Simon, Eva Trost, Klaus Stark, Christina Frank
Journal: Eurosurveillance (2025)

Background Enteric fevers (EF) are caused by infections with Salmonella Typhi (STY) or Salmonella Paratyphi (SP) A-C (except the SPB enteric pathovar) and exhibit increasing antimicrobial resistance (AMR). Notification is mandatory in Germany. Aim To describe characteristics and trends of notified EF cases in Germany. Methods We analysed German EF notifications 2001–2023 fulfilling the case definition. We calculated numbers of imported EF cases per 100,000 air travellers by country of exposure 2012–2023. Results In 2001–2023, 2,670 confirmed EF cases were notified: 56% (1,498/2,670) STY, 44% (1,172/2,670) SP, with seasonal peaks in April–May and August–September. Aside from years with COVID-19-related travel restrictions, STY notifications were stable, while SP notifications decreased. Median age of EF cases was 26 years (range: 0–93) and 55% (1,458/2,663) were male. Of cases with information, 93% (2,491/2,670) had fever, 71% (1,906/2,670) diarrhoea, 78% (2,033/2,607) were hospitalised (STY: 85% (1,234/1,459) vs SP: 70% (799/1,148), p &lt; 0.001) and four died (two STY, one SPA, one SPB). Of STY cases, 7% (88/1,221) reported vaccination. Overall, 86% (2,251/2,613) of cases acquired EF abroad, most commonly in India, Pakistan and Türkiye. Ciprofloxacin resistance was reported for 50/59 STY and 16/18 SPA cases and cefotaxime resistance for 10/57 STY cases (exposure: Pakistan (9/10), India (1/10)) with information since 2017. We also report outbreaks and incidence among travellers. Conclusions Most cases were imported and had high hospitalisation rates and AMR. Typhoid vaccination was underutilised, highlighting that additional ways to reach at-risk travellers with information and vaccination offers are needed.
Investigation of an outbreak of novel hepatitis of unknown aetiology in children and adolescents, Ireland, 2021 to 2023
Authors: Emer Liddy, Niamh Murphy, Jolita Mereckiene, Emer Fitzpatrick, Annemarie Broderick, Róisin Egan, Tiarnán Fallon Verbruggen, Julie-Anne Houlihan, Christine Campbell, Michael Carr, Gabriel Gonzalez, Jonathan Dean, Richard Hagan, Cillian De Gascun, Suzanne Cotter
Journal: Eurosurveillance (2025)

An outbreak of severe acute hepatitis of unknown aetiology in children (HUAC) was reported by the United Kingdom (UK) in spring 2022. Within days, a corresponding increase was identified in Ireland. A multi-agency incident management team (IMT), led by the Health Protection Surveillance Centre (HPSC), established a national case definition, trawling questionnaire, testing protocol and communications plan. Between 1 October 2021 and 12 May 2023, 44 probable and three possible cases of HUAC were identified in Ireland with a median age of 3 years. Adeno-associated virus 2 (AAV2), detected in 18 of 31 probable cases, and SARS-CoV-2 antibodies in 22 of 37 of probable cases were the most common infectious agents, followed by human herpes virus 7 (18/33) and adenovirus (20/44). Immunological findings included the human leukocyte antigen (HLA) class II HLA-DRB1*04:01 allele in 17 of 32 cases. Autoantibodies were found in 15 of 40 patients. Our findings corroborate those of the UK, which suggested a link between HUAC and AAV2 and another virus, in children predisposed due to presence of a particular HLA class II type. Close collaboration with the UK, the European Centre for Disease Prevention and Control (ECDC) and World Health Organization (WHO) was invaluable in the investigation.
Cholera due to exposure in Europe associated with consumption of holy water from Ethiopia, January to February 2025
Authors: Christina Frank, Claire Jenkins, Jana-Marie Weis, Anja Brilmayer, Anja Schoeps, Susann Dupke, Hendrik Wilking, Parisha Katwa, Satheesh Nair, Clare Barker, Derren Ready, Gauri Godbole, Susan Hopkins, Hilary Kirkbride
Journal: Eurosurveillance (2025)

In February 2025, public health agencies in Germany and the United Kingdom (UK) reported four cases of domestically acquired cholera caused by consumption of holy water imported from Ethiopia, and a further three cases in travellers to Ethiopia. Multidrug-resistant Vibrio cholerae O1, linked to recent outbreaks in Eastern and Middle Africa, was detected in clinical specimens and the holy water. In cholera-endemic regions, visitors should drink potable water and should not bring bottled water back from their travels.
Outbreak of Neisseria meningitidis serogroup B in Aragón, Spain, January to February 2025
Authors: Cristina Nicolau Cano, Alba Gallego-Royo, Esteban Estupiñan Valido, Alejandra Perez Perez, Teresa Gimenez Julvez, Berta Maria Pilar Vela Iglesia, Maria Carmen Montaño Remacha
Journal: Eurosurveillance (2025)

In January–February 2025, a community outbreak of Neisseria meningitidis serogroup B was reported in Aragón, Spain, with nine confirmed cases. This represents a 27-fold increase vs the previous 3 years. Five cases had respiratory co-infections; seven were attributed to complex CC213. Epidemiological investigations revealed a potential link to a school setting, though direct transmission could not be confirmed. These findings highlight the need to reinforce surveillance during periods of high respiratory virus circulation and in outbreaks involving non-4CMenB-covered variants.
Gut microbiota and epigenetic inheritance: implications for the development of IBD
Authors: Xue Guo, Jianhong Li, Jing Xu, Leiting Zhang, Chen Huang, Yuqiang Nie, Youlian Zhou
Journal: Gut Microbes (2025)

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is considered significant global health concerns worldwide. Many studies have demonstrated that environmental and dietary factors influence the gut microbiota, which in turn orchestrates the host immune responses. These interactions are also involved in complex metabolic processes that contribute to the pathogenesis of IBD. Furthermore, recent studies in genomics and metabolomics have unveiled the intricate relationship between microbial influencers and host epigenetics. The dynamics of gut microbiota and its metabolites intricately align with DNA methylation, histone methylation, lactylation, glycosylation, and non-coding RNAs, which are key players in epigenetics. Here, we summarize and discuss the complex interplay among gut microbiota, epigenetics, and environmental and dietary factors, and their impact on the pathogenesis of IBD. Furthermore, we highlight the importance of multi-omics technologies in dissecting the host-microbe interactions in IBD, potentially offering a framework for developing effective treatment strategies.
Clinical translation of microbiome research
Authors: Jack A Gilbert, Meghan B Azad, Fredrik Bäckhed, Martin J Blaser, Mariana Byndloss, Charles Y Chiu, Hiutung Chu, Lara R Dugas, Eran Elinav, Sean M Gibbons, Katharine E Gilbert, Matthew R Henn, Suzanne L Ishaq, Ruth E Ley, Susan V Lynch, Eran Segal, Tim D Spector, Philip Strandwitz, Jotham Suez, Carolina Tropini, Katrine Whiteson, Rob Knight
Journal: Nature Medicine (2025)
IVF versus ICSI in patients without severe male factor infertility: a randomized clinical trial
Authors: Sine Berntsen, Anne Zedeler, Bugge Nøhr, Morten Rønn Petersen, Marie Louise Grøndahl, Lars Franch Andersen, Kristine Løssl, Ellen Løkkegaard, Anne Lis Englund, Anette Vestergaard Gabrielsen, Lisbeth Prætorius, Ida Behrendt-Møller, Lea Langhoff Thuesen, Kilian Vomstein, Mette Petri Lauritsen, Aleksandra Ivanoska Trajcevski, Dea Frøding Skipper, David Westergaard, Anja Pinborg, Henriette Svarre Nielsen, Nina la Cour Freiesleben
Journal: Nature Medicine (2025)
Enterovirus circulation in the WHO European region, 2015–2022: a comparison of data from WHO's three core poliovirus surveillance systems and the European Non-Polio Enterovirus Network (ENPEN)
Authors: Heli Harvala, Caroline K Johannesen, Kimberley S M Benschop, Eugene V Saxentoff, Shahin Huseynov, José E Hagan, Thea K Fischer
Journal: The Lancet Regional Health - Europe (2025)
Interferon-γ-mediated selective inhibition of hematopoiesis and the clonal advantage of HLA-lacking hematopoietic stem progenitor cells in aplastic anemia
Authors: Rio Takahashi, Honoka Takahashi, Luna Seoka, Hiroka Iwasaki, Hiroyuki Takamatsu, Tatsuya Imi, Yoshitaka Zaimoku, Kohei Hosokawa, Takamasa Katagiri
Journal: Leukemia (2025)
Phase II study evaluating the safety and efficacy of neratinib and trastuzumab biosimilar in patients with <i>HER2</i> mutated advanced solid tumors: KCSG AL20‐17/KM23 trial
Authors: Kyoungmin Lee, Kyung‐Hun Lee, Dong‐Wan Kim, Jeesun Yoon, Yoon Ji Choi, Soohyeon Lee, Ju Won Kim, Kyong Hwa Park, Wonyoung Choi, Youngjoo Lee, Hyewon Ryu, Dong‐Hoe Koo, YunGyoo Lee, Hei‐Cheul Jeung, Min‐Young Lee, Namsu Lee, Myoung Joo Kang, Jieun Lee, Sook Hee Hong, Eun Joo Kang, In Hae Park
Journal: Cancer Communications (2025)
Microbiota-shaped neutrophil senescence regulates sexual dimorphism in bladder cancer
Authors: Qingchen Zhu, Guiheng Zhang, Ming Cao, Huan Huang, Dan He, Zhongsheng Zang, Jing Xing, Ming Zhan, Siyu Pei, Xiuyu Deng, Juan Li, Guangxun Meng, Jing Xu, Dongfang Dai, Guohong Hu, Mingyue Zheng, Chenli Liu, Jun Qin, Yichuan Xiao
Journal: Nature Immunology (2025)
Sacituzumab tirumotecan in previously treated metastatic triple-negative breast cancer: a randomized phase 3 trial
Authors: Yongmei Yin, Ying Fan, Quchang Ouyang, Lihua Song, Xiaojia Wang, Wei Li, Man Li, Xi Yan, Shusen Wang, Tao Sun, Yuee Teng, Xianjun Tang, Zhongsheng Tong, Zhengkui Sun, Junyou Ge, Xiaoping Jin, Yina Diao, Gesha Liu, Binghe Xu
Journal: Nature Medicine (2025)
NK cell-derived IFNγ mobilizes free fatty acids from adipose tissue to promote early B cell activation during viral infection
Authors: Mia Krapić, Inga Kavazović, Sanja Mikašinović, Karlo Mladenić, Fran Krstanović, Gönül Seyhan, Sabine Helmrath, Elena Camerini, Ilija Brizić, Fleur S Peters, Marc Schmidt-Supprian, Bojan Polić, Tamara Turk Wensveen, Felix M Wensveen
Journal: Nature Metabolism (2025)
Pre-symptomatic Parkinson’s disease blood test quantifying repetitive sequence motifs in transfer RNA fragments
Authors: Nimrod Madrer, Shani Vaknine-Treidel, Tamara Zorbaz, Yonat Tzur, Estelle R Bennett, Paz Drori, Nitzan Suissa, David S Greenberg, Eitan Lerner, Eyal Soreq, Iddo Paldor, Hermona Soreq
Journal: Nature Aging (2025)
Metal-Organic Frameworks as Therapeutic Chameleons: Revolutionizing the Cancer Therapy Employing Novel Nanoarchitectonics
Authors: Sajja Bhanu Prasad, Akshay Shinde, Dadi A. Srinivasrao, Paras Famta, Saurabh Shah, Tejaswini Kolipaka, Giriraj Pandey, Deelip Gaonker, Ganesh Vambhurkar, Pooja Khairnar, Rahul Kumar, Amol G Dikundwar, Vinaykumar Kanchupalli, Saurabh Srivastava
Journal: Asian Journal of Pharmaceutical Sciences (2025)
Modified mRNA Treatment Restores Cardiac Function in Desmocollin-2–Deficient Mouse Models of Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Yan Zou, Jing Lu, Zhipeng Lian, Jianguo Jia, Juan Shen, Qianhe Li, Jennifer Ming Jen Wong, Kejia Jin, Wendi Yan, Xinyue Ren, Yang Zhang, Chenxing Huang, Huanjie Yang, Feng Huang, Jun Li, Junyu Zhai, Yamei Xu, Xialian Xu, Hang Yu, Yi Jin, Hui Gong, Jinzhong Lin, Junbo Ge, Yuxiang Dai
Journal: Circulation (2025)

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart disease characterized by irregular rhythms and right ventricular dysplasia. Sequence variations in desmosomal protein-encoding genes are linked to ARVC development. Effective treatments for ARVC are lacking. Whereas mRNA-based therapies have shown efficacy in humans, their therapeutic potential for inherited cardiomyopathies remains unclear. METHODS: Whole-exome sequencing identified a novel DSC2 sequence variation causing autosomal recessive ARVC in a Chinese family with consanguineous marriage. Mouse models with Dsc2 sequence variation knock-in and constitutive knock-out were generated and analyzed using echocardiography and histology. Transcriptomic and biochemical analyses were conducted to explore ARVC mechanisms. Dsc2 mRNA delivered by intracardiac or transcoronary injection was assessed as a treatment for ARVC in Dsc2 knock-out mice. In addition, effects of Dsc2 mRNA were examined in a transverse aortic constriction mouse model with noninherited right ventricular systolic dysfunction. RESULTS: Dsc2 -deficient mice exhibited right ventricular dilation and dysfunction, mimicking human disease. Transcriptomic analysis identified Myl7 as the most downregulated gene in the right ventricles of Dsc2 -deficient mice, and its restoration by adeno-associated virus 9 rescued heart function. Dsc2 mRNA delivery, with or without lipid nanoparticle encapsulation, normalized heart size and function in Dsc2 -deficient mice. Reduced DSC2 and MLC2a expression was also noted in patients with noninherited dilated cardiomyopathy and in mice with transverse aortic constriction. A single dose of mRNA provided therapeutic effects lasting 2 to 3 months before declining. CONCLUSIONS: Our study reveals novel mechanisms of ARVC caused by DSC2 loss of function, supported by human and mouse data. Loss of Myl7 contributes to reduced cardiac contractility in ARVC and dilated cardiomyopathy with right ventricular systolic dysfunction. Dsc2 mRNA treatment demonstrated significant therapeutic potential in ARVC and transverse aortic constriction models, providing a basis for future clinical applications.
Chromatin Rewiring by SETD2 Drives Lipotoxic Injury in Cardiometabolic HFpEF
Authors: Sarah Costantino, Shafeeq A. Mohammed, Samuele Ambrosini, Marialucia Telesca, Alessandro Mengozzi, Kaivalya Walavalkar, Era Gorica, Melissa Herwig, Loek van Heerebeek, Junyan Xia, Gergely Karsai, Thorsten Hornemann, Omer Dzemali, Raffaella Santoro, Qian Li, Frank Ruschitzka, Nazha Hamdani, Francesco Paneni
Journal: Circulation Research (2025)

BACKGROUND: Cardiometabolic heart failure with preserved ejection fraction (cHFpEF) is a highly prevalent and deadly condition. Histone 3 trimethylation at lysine 36 (H3k36me3)—a chromatin signature induced by the histone methyltransferase SETD2 (SET domain containing 2)—correlates with changes in gene expression in human failing hearts; however, its role remains poorly understood. This study investigates the role of SETD2 in cHFpEF. METHODS: Chromatin immunoprecipitation sequencing and RNA sequencing were used to investigate H3k36me3-related transcriptional regulation. Mice with cardiomyocyte-specific deletion of SETD2 (c-SETD2 −/− ) were generated and subjected to high-fat diet feeding and L-NAME treatment for 15 weeks to induce cHFpEF. Cardiac function and exercise tolerance were assessed by echocardiography and treadmill exhaustion test. A selective pharmacological inhibitor of SETD2, EZM0414, was also tested in cHFpEF mice. Mechanistic experiments were performed in cultured cardiomyocytes exposed to palmitic acid. SETD2 signaling and the effects of EZM0414 were also investigated in cardiomyocytes from patients with cHFpEF and control donors. RESULTS: SETD2 was upregulated in cHFpEF mouse hearts, and its chromatin mark H3k36me3 was involved in lipid metabolism and highly enriched on the promoter of the Srebf1 gene, encoding for SREBP1 (sterol regulatory binding protein 1). SETD2 activation in cHFpEF led to SREBP1 upregulation, triglyceride accumulation, and lipotoxic damage. Of note, cardiomyocyte-specific deletion of SETD2 in mice prevented heart failure with preserved ejection fraction–related hypertrophy, diastolic dysfunction, and lung congestion while improving exercise tolerance. SETD2 deletion blunted H3K36me3 enrichment on Srebf1 promoter, thus leading to a marked rewiring of the cardiac lipidome and restoration of autophagic flux. In vivo treatment with the SETD2 inhibitor EZM0414 recapitulated the effects of SETD2 deletion. Silencing of SETD2 in palmitic acid–treated cardiomyocytes prevented SREBP1 upregulation, whereas SETD2 overexpression mirrored lipotoxic damage. Finally, SETD2 was upregulated in left ventricle specimens from patients with cHFpEF while EZM0414 attenuated cardiomyocyte stiffness. CONCLUSIONS: Targeting SETD2 might prevent lipotoxic injury in cHFpEF.
Heart Has Intrinsic Ketogenic Capacity that Mediates NAD <sup>+</sup> Therapy in HFpEF
Authors: Yen Chin Koay, Bailey McIntosh, Yann Huey Ng, Yang Cao, XiaoSuo Wang, Yanchuang Han, Saki Tomita, Angela Yu Bai, Benjamin Hunter, Ashish Misra, Christopher M. Loughrey, Paul G. Bannon, Sean Lal, Aldons J. Lusis, David M. Kaye, Mark Larance, John F. O’Sullivan
Journal: Circulation Research (2025)

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) has overtaken heart failure with reduced ejection fraction as the leading type of heart failure globally and is marked by high morbidity and mortality rates, yet with only a single approved pharmacotherapy: SGLT2i (sodium-glucose co-transporter 2 inhibitor). A prevailing theory for the mechanism underlying SGLT2i is nutrient deprivation signaling, of which ketogenesis is a hallmark. However, it is unclear whether the canonical ketogenic enzyme, HMGCS2 (3-hydroxy-3-methylglutaryl-coenzyme A synthase 2), plays any cardiac role in HFpEF pathogenesis or therapeutic response. METHODS: We used human myocardium, human HFpEF and heart failure with reduced ejection fraction transcardiac blood sampling, an established murine model of HFpEF, ex vivo Langendorff perfusion, stable isotope tracing in isolated cardiomyocytes, targeted metabolomics, proteomics, lipidomics, and a novel cardiomyocyte-specific conditional HMGCS2-deficient model that we generated. RESULTS: We demonstrate, for the first time, the intrinsic capacity of the human heart to produce ketones via HMGCS2. We found that increased acetylation of HMGCS2 led to a decrease in the enzyme’s specific activity. However, this was overcome by an increase in the steady-state levels of protein. Oxidized form of nicotinamide adenine dinucleotide repletion restored HMGCS2 function via deacetylation, increased fatty acid oxidation, and rescued cardiac function in HFpEF. Critically, using a conditional, cardiomyocyte-specific HMGCS2 knockdown murine model, we revealed that the oxidized form of nicotinamide adenine dinucleotide is unable to rescue HFpEF in the absence of cardiomyocyte HMGCS2. CONCLUSIONS: The canonical ketogenic enzyme, HMGCS2, mediates the therapeutic effects of the oxidized form of nicotinamide adenine dinucleotide repletion in HFpEF by restoring normal lipid metabolism and mitochondrial function.
Orally-Deliverable Liposome-Microgel Complexes Dynamically Remodel Intestinal Environment to Enhance Probiotic Ulcerative Colitis Therapy via TLR4 Inhibition and Tryptophan Metabolic Crosstalk
Authors: Yuanyuan Fu, Ting Wang, Xinyue Ge, Hong Wen, Yang Fei, Menghuan Li, Zhong Luo
Journal: Biomaterials (2025)
Multiplex imaging of murine bone marrow using Phenocycler 2.0™
Authors: Sonali J Karnik, Connor Gulbronson, Paige C Jordan, Rahul Kanumuri, Baskar Ramdas, Ramesh Kumar, Melissa L Hartman, Izza Khurram, Drew M Brown, Karen E Pollok, Pratibha Singh, Reuben Kapur, Melissa A Kacena
Journal: Leukemia (2025)
Estimating endurance training intensity prescription from the 6-minute stepper test in people with chronic obstructive pulmonary disease – a multicenter cross-sectional study with external validation
Authors: Tristan Bonnevie, Augustin Clet, Marc Beaumont, Pauline Smondack, Yann Combret, Clément Médrinal, Guillaume Prieur, Fairuz Boujibar, Jean-François Muir, Antoine Cuvelier, Jean-Marie Grosbois, David Debeaumont, Elise Artaud-Macari, Francis-Edouard Gravier
Journal: Pulmonology (2025)

Home-based pulmonary rehabilitation (PR) can enhance accessibility to PR, but no at-home field exercise test has been validated for individualized endurance training prescriptions. What is the accuracy of the six-minute stepper test (6MST) in estimating endurance training intensity as determined during cardiopulmonary exercise testing (CPET)? This multicenter (N = 3) cross-sectional study included individuals with COPD. Participants performed CPET and two 6MSTs to evaluate the 6MST's ability to estimate endurance training intensity based on CPET-derived heart rate at the first ventilatory threshold (HRvt1), the corresponding power output (Pvt1), and peak power output (Ppeak). Predictive equations were tested for external validity using data from two prior studies. 105 patients were included (mean age 61 (SD 9) years; mean FEV1 61 (SD 21) %). Predictive equations moderately predicted HRvt1 (r² = 0.38), strongly predicted Pvt1 (r² = 0.63) and very strongly predicted Ppeak (r² = 0.75). External validity was small to moderate for HRvt1 and Pvt1 but was strong for 60% of Ppeak (mean absolute difference: 10W, 95% CI 5 to 10). Passing and Bablok regression confirmed interchangeability for Pvt1 and 60% of Ppeak. The 6MST offers a reliable method to set initial training intensity when CPET is unavailable. NCT02842463.