tbuckley/cabot-search huggingface dataset:
Hospitalisation due to respiratory syncytial virus in a population-based cohort of older adults in Spain, 2016/17 to 2019/20
Authors: Noelia Vera-Punzano, Camino Trobajo-Sanmartín, Ana Navascués, Aitziber Echeverria, Itziar Casado, Carmen Ezpeleta, Jesús Castilla, Iván Martínez-Baz
Journal: Eurosurveillance (2025)

Background Respiratory syncytial virus (RSV) is a major cause of acute respiratory infection that can lead to complications in risk groups. Aim We aimed to estimate the incidence of RSV hospitalisation in adults, determine the risk factors and characterise priority groups for prevention. Methods This population-based cohort study included adults 60 years and older in Navarre, Spain, in seasons 2016/17 to 2019/20. We estimated the rate of RSV hospitalisation confirmed by PCR and evaluated risk factors using Poisson regression. Results Within 642,622 person-years analysed, we detected 544 RSV hospitalisations (average annual rate: 84.7/100,000). The rate varied among seasons between 59.7 and 95.6 per 100,000. The rate ratio of hospitalisation was higher than 3 from the age of 75 years and around 7 in the 85–94 years age group compared with those aged 60–64 years. Nursing home residence, functional dependence, haematological cancer, chronic obstructive pulmonary disease (COPD), asthma, cardiovascular disease, severe obesity, diabetes and chronic kidney disease were independent risk conditions. Rate of RSV hospitalisation was higher than 300 per 100,000 among people with haematological cancer or nursing home residence, those aged ≥ 75 years with COPD or functional dependence, and those aged ≥ 85 years with asthma or cardiovascular disease. These groups represented 13.2% of all adults aged ≥ 60 years and 50.7% of their RSV hospitalisations. On average, these groups had one RSV hospitalisation per 307 person-years. Conclusion Advanced age, in addition to nursing home residence, functional dependence and some comorbidities define priority groups for RSV vaccination.
Case series of the first five human infections with monkeypox virus clade Ib and report on the public health response, United Kingdom, October to November 2024
Authors: Muhammad Ibaad Alvi, Merav Kliner, William Welfare, N Claire Gordon, Sherine Thomas, Simon Padfield, Hannah E Emmett, Ellen Heinsbroek, Gareth J Hughes, Natalie Groves, Eileen Gallagher, Steven Pullan, Amy Belfield, Catherine F Houlihan, Tommy Rampling, Geraldine O’Hara, Anne Tunbridge, Jake Dunning, Elizabeth Whittaker, Alejandra Alonso, Mike Beadsworth, Brendan AI Payne, Meera Chand, Susan Hopkins, Gillian Armstrong
Journal: Eurosurveillance (2025)

We report two importations of monkeypox virus clade Ib infection to the United Kingdom in 2024. The first was a traveller returning from Tanzania, Rwanda and Uganda, the second from Uganda. Both presented with fever and typical skin lesions; 147 contacts were followed up, 19 vaccinated with MVA-BN. Three household contacts of the first individual, including two children, became infected. These are the first reported autochthonous transmissions of clade Ib in Europe, and first paediatric cases outside the African continent.
Quasi-species prevalence and clinical impact of evolving SARS-CoV-2 lineages in European COVID-19 cohorts, January 2020 to February 2022
Authors: Matilda Berkell, Anna Górska, Mathias Smet, Delphine Bachelet, Elisa Gentilotti, Mariana Guedes, Anna Maria Franco-Yusti, Fulvia Mazzaferri, Erley Lizarazo Forero, Veerle Matheeussen, Benoit Visseaux, Zaira R. Palacios-Baena, Natascia Caroccia, Aline-Marie Florence, Charlotte Charpentier, Coretta van Leer, Maddalena Giannella, Alex W. Friedrich, Jesús Rodríguez-Baño, Jade Ghosn, Samir Kumar-Singh, Cedric Laouénan, Evelina Tacconelli, Surbhi Malhotra-Kumar
Journal: Eurosurveillance (2025)

Background Evolution of SARS-CoV-2 is continuous. Aim Between 01/2020 and 02/2022, we studied SARS-CoV-2 variant epidemiology, evolution and association with COVID-19 severity. Methods In nasopharyngeal swabs of COVID-19 patients (n = 1,762) from France, Italy, Spain, and the Netherlands, SARS-CoV-2 was investigated by reverse transcription-quantitative PCR and whole-genome sequencing, and the virus variant/lineage (NextStrain/Pangolin) was determined. Patients’ demographic and clinical details were recorded. Associations between mild/moderate or severe COVID-19 and SARS-CoV-2 variants and patient characteristics were assessed by logistic regression. Rates and genomic locations of mutations, as well as quasi-species distribution (≥ 2 heterogeneous positions, ≥ 50× coverage) were estimated based on 1,332 high-quality sequences. Results Overall, 11 SARS-CoV-2 clades infected 1,762 study patients of median age 59 years (interquartile range (IQR): 45–73), with 52.5% (n = 925) being male. In total, 101 non-synonymous substitutions/insertions correlated with disease prognosis (severe, n = 27; mild-to-moderate, n = 74). Several hotspots (mutation rates ≥ 85%) occurred in Alpha, Delta, and Omicron variants of concern (VOCs) but none in pre-Alpha strains. Four hotspots were retained across all study variants, including spike:D614G. Average number of mutations per open-reading-frame (ORF) increased in the spike gene (average &lt; 5 per genome in January 2020 to &gt; 15 in 2022), but remained stable in ORF1ab, membrane, and nucleocapsid genes. Quasi-species were most prevalent in 20A/EU2 (48.9%), 20E/EU1 (48.6%), 20A (38.8%), and 21K/Omicron (36.1%) infections. Immunocompromised status and age (≥ 60 years), while associated with severe COVID-19 or death irrespective of variant (odds ratio (OR): 1.60–2.25; p ≤ 0.014), did not affect quasi-species’ prevalence (p &gt; 0.05). Conclusion Specific mutations correlate with COVID-19 severity. Quasi-species potentially shaping VOCs’ emergence are relevant to consider.
A case report of a cat infected with European bat lyssavirus type 1, the Netherlands, October 2024
Authors: Phaedra Eblé, Aldo Dekker, Sanne van den End, Vanessa Visser, Marc Engelsma, Frank Harders, Lucien van Keulen, Erik van Weezep, Melle Holwerda
Journal: Eurosurveillance (2025)

In October 2024, an infection of European bat lyssavirus type 1 was confirmed in a domestic cat in the Netherlands. Several weeks before, the owners had found a dead bat considered to be caught by the cat. Nine persons exposed to the cat received post-exposure prophylaxis and four domestic animals from the same household were quarantined. This report stresses the need for vigilance for rabies in domestic animals in countries where lyssavirus infections in bats are endemic.
Impact of SARS-CoV-2 variant mutations on susceptibility to monoclonal antibodies and antiviral drugs: a non-systematic review, April 2022 to October 2024
Authors: Maja Vukovikj, Angeliki Melidou, Priyanka Nannapaneni, Tanja Normark, Annette Kraus, Eeva K Broberg
Journal: Eurosurveillance (2025)

Background Monoclonal antibodies (mAbs) and antiviral drugs have emerged as additional tools for treatment of COVID-19. Aim We aimed to review data on susceptibility of 14 SARS-CoV-2 variants to mAbs and antiviral drugs authorised in the European Union/European Economic Area (EU/EEA) countries. Methods We constructed a literature review compiling 298 publications from four databases: PubMed, Science Direct, LitCovid and BioRxiv/MedRxiv preprint servers. We included publications on nirmatrelvir and ritonavir, remdesivir and tixagevimab and cilgavimab, regdanvimab, casirivimab and imdevimab, and sotrovimab approved by the European Medicines Agency (EMA) by 1 October 2024. Results The mutations identified in the open reading frame (ORF)1ab, specifically nsp5:H172Y, nsp5:H172Y and Q189E, nsp5:L50F and E166V and nsp5:L50F, E166A and L167V, led to a decrease in susceptibility to nirmatrelvir and ritonavir, ranging from moderate (25-99) to high reductions (&gt; 100). Casirivimab and imdevimab exhibited highly reduced neutralisation capacity across all Omicron sub-lineages. Sub-lineages BA.1, BA.2 and BA.5 had decreased susceptibility to regdanvimab, while sotrovimab showed decreased efficacy for BA.2, BA.4, BQ.1.1 and BA.2.86. Tixagevimab and cilgavimab exhibited highly reduced neutralisation activity against BQ.1, BQ.1.1, XBB, XBB.1.5 and BA.2.86 sub-lineages. Conclusions The emergence of new variants, some with altered antigenic characteristics, may lead to resistance against mAbs and/or antiviral drugs and evasion of immunity induced naturally or by vaccination. This summary of mutations, combination of mutations and SARS-CoV-2 variants linked to reduced susceptibility to mAbs and antiviral drugs, should aid the selection of appropriate treatment strategies and/or phasing out therapies that have lost their effectiveness.
Hospital admissions attributable to reduced air pollution due to clean-air policies in China
Authors: Huimeng Liu, Jian Lei, Yuewei Liu, Tong Zhu, Kahung Chan, Xi Chen, Jing Wei, Furong Deng, Ge Li, Yunxing Jiang, Lijun Bai, Kai Wang, Juan Chen, Yang Lan, Xi Xia, Jinxi Wang, Chen Wei, Yinxiang Li, Renjie Chen, Jicheng Gong, Xiaoli Duan, Kai Zhang, Haidong Kan, Xiaoming Shi, Xinbiao Guo, Shaowei Wu
Journal: Nature Medicine (2025)
Composition of plant-based diets and the incidence and prognosis of inflammatory bowel disease: a multinational retrospective cohort study
Authors: Jie Chen, Yuhao Sun, Lintao Dan, Judith Wellens, Shuai Yuan, Hong Yang, Tammy Y N Tong, Amanda J Cross, Nikos Papadimitriou, Antoine Meyer, Christina C Dahm, Susanna C Larsson, Alicja Wolk, Jonas F Ludvigsson, Kostas Tsilidis, Edward Giovannucci, Jack Satsangi, Xiaoyan Wang, Evropi Theodoratou, Simon S M Chan, Xue Li
Journal: The Lancet Regional Health - Europe (2025)
Proteogenomic characterization of molecular and cellular targets for treatment-resistant subtypes in locally advanced cervical cancers
Authors: Do Young Hyeon, Dowoon Nam, Hye-Jin Shin, Juhee Jeong, Eunsoo Jung, Soo Young Cho, Dong Hoon Shin, Ja-Lok Ku, Hye Jung Baek, Chong Woo Yoo, Eun-Kyung Hong, Myong Cheol Lim, Sang-Jin Lee, Young-Ki Bae, Jong Kwang Kim, Jingi Bae, Wonyoung Choi, Su-Jin Kim, Seunghoon Back, Chaewon Kang, Inamul Hasan Madar, Hokeun Kim, Suhwan Kim, Duk Ki Kim, Jihyung Kang, Geon Woo Park, Ki Seok Park, Yourae Shin, Sang Soo Kim, Keehoon Jung, Daehee Hwang, Sang-Won Lee, Joo-Young Kim
Journal: Molecular Cancer (2025)

We report proteogenomic analysis of locally advanced cervical cancer (LACC). Exome-seq data revealed predominant alterations of keratinization-TP53 regulation and O-glycosylation-TP53 regulation axes in squamous and adeno-LACC, respectively, compared to in early-stage cervical cancer. Integrated clustering of mRNA, protein, and phosphorylation data identified six subtypes (Sub1-6) of LACC among which Sub3, 5, and 6 showed the treatment-resistant nature with poor local recurrence-free survival. Elevated immune and extracellular matrix (ECM) activation mediated by activated stroma (PDGFD and CXCL1high fibroblasts) characterized the immune-hot Sub3 enriched with MUC5AChigh epithelial cells (ECs). Increased epithelial-mesenchymal-transition (EMT) and ECM remodeling characterized the immune-cold squamous Sub5 enriched with PGK1 and CXCL10high ECs. We further demonstrated that CIC mutations could trigger EMT activation by upregulating ETV4, and the elevation of the immune checkpoint PVR and neutrophil-like myeloid-derived suppressive cells (FCN1 and FCGR3Bhigh macrophages) could cause suppression of T-cell activation in Sub5. Increased O-linked glycosylation of mucin characterized adeno-LACC Sub6 enriched with MUC5AChigh ECs. These results provide a battery of somatic mutations, cellular pathways, and cellular players that can be used to predict treatment-resistant LACC subtypes and can serve as potential therapeutic targets for these LACC subtypes.
Nanotechnology-leveraged CRISPR/Cas systems: icebreaking in trace cancer-related nucleic acids biosensing
Authors: Weipan Peng, Mengting Shi, Bin Hu, Jingyu Jia, Xinyue Li, Nan Wang, Shuli Man, Shengying Ye, Long Ma
Journal: Molecular Cancer (2025)

As promising noninvasive biomarkers, nucleic acids provide great potential to innovate cancer early detection methods and promote subsequent diagnosis to improve the survival rates of patient. Accurate, straightforward and sensitive detection of such nucleic acid-based cancer biomarkers in complex biological samples holds significant clinical importance. However, the low abundance creates huge challenges for their routine detection. As the next-generation diagnostic tool, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein (Cas) with their high programmability, sensitivity, fidelity, single-base resolution, and precise nucleic acid positioning capabilities are extremely attractive for trace nucleic acid-based cancer biomarkers (NABCBs), permitting rapid, ultra-sensitive and specific detection. More importantly, by combing with nanotechnology, it can solve the long-lasting problems of poor sensitivity, accuracy and simplicity, as well as to achieve integrated miniaturization and portable point-of-care testing (POCT) detection. However, existing literature lacks specific emphasis on this topic. Thus, we intend to propose a timely one for the readers. This review will bridge this gap by providing insights for CRISPR/Cas-based nano-biosensing development and highlighting the current state-of-art, challenges, and prospects. We expect that it can provide better understanding and valuable insights for trace NABCBs detection, thereby facilitating advancements in early cancer screening/detection/diagnostics and win practical applications in the foreseeable future.
Social disadvantage accelerates aging
Authors: Mika Kivimäki, Jaana Pentti, Philipp Frank, Fangyu Liu, Acer Blake, Solja T. Nyberg, Jussi Vahtera, Archana Singh-Manoux, Tony Wyss-Coray, Keenan A. Walker, Linda Partridge, Joni V. Lindbohm
Journal: Nature Medicine (2025)

Abstract Social disadvantage, like advanced age, is a risk factor for a broad range of health conditions; however, whether it influences the aging process remains unclear. Here, using a multicohort approach, we investigated the associations of social disadvantage with age-related plasma proteins and age-related diseases. We found proteomic signatures of accelerated immune aging and 14 specific age-related proteins linked to social disadvantage during both early and later life. Individuals experiencing social disadvantage had an increased risk of 66 age-related diseases, with up to 39% of these associations mediated by the 14 age-related proteins (for example, DNAJB9, F2, HSPA1A, BGN). The main enriched pathway involved the upregulation of the pro-inflammatory regulator NF-κB24 and its downstream factor interleukin-8. Our findings support the hypothesis that social disadvantage throughout the life course may accelerate aging, a biological mechanism that could explain why social stratification plays such a fundamental role in determining human health.
Human gut microbial aromatic amino acid and related metabolites prevent obesity through intestinal immune control
Authors: Zengliang Jiang, Liuqing He, Diyin Li, Laibao Zhuo, Lingjun Chen, Rui-Qi Shi, Jianhua Luo, Yuhui Feng, Yuhui Liang, Danyang Li, Xiao Congmei, Yuanqing Fu, Yu-ming Chen, Ju-Sheng Zheng, Liang Tao
Journal: Nature Metabolism (2025)

Obesity affects millions of people in the world. The gut microbiome influences body fat accumulation, but the mechanisms remain to be investigated. Here, we show an association between microbial aromatic amino acid metabolites in serum and body fat accumulation in a large Chinese longitudinal cohort. We next identify that 4-hydroxyphenylacetic acid (4HPAA) and its analogues effectively protect male mice from high-fat-diet-induced obesity. These metabolites act on intestinal mucosa to regulate the immune response and control lipid uptake, which protects against obesity. We further demonstrate that T cells and B cells are not vital for 4HPAA-mediated obesity prevention, and innate lymphoid cells have antagonistic roles. Together, these findings reveal specific microbial metabolites as pivotal molecules to prohibit obesity through immune control, establishing mechanisms of host modulation by gut microbial metabolites. The gut-microbiota-derived aromatic amino acid metabolite 4-hydroxyphenylacetic acid (4HPAA) and its analogues have been shown to protect against obesity. In mice, 4HPAA exerts anti-obesogenic effects by modulating mucosal immunity and lipid uptake in the intestine.
SIRT5 safeguards against primate skeletal muscle ageing via desuccinylation of TBK1
Authors: Qian Zhao, Ying Jing, Xiaoyu Jiang, Xin Zhang, Feifei Liu, Haoyan Huang, Zhihua Zhang, Haijun Wang, Shuhui Sun, Shuai Ma, Weiqi Zhang, Yang Yu, Xiaobing Fu, Guoguang Zhao, Jing Qu, Si Wang, Guang-Hui Liu
Journal: Nature Metabolism (2025)
Effects of secukinumab on enthesiophyte and erosion progression in psoriatic arthritis –a one‐year double‐blind, randomized, placebo‐controlled trial utilizing high‐resolution peripheral quantitative computed tomography
Authors: Yingzhao Jin, Isaac T Cheng, Ho So, Billy T Lai, Shirley K. Ying, Kitty Y. Kwok, James Griffith, Vivian Hung, Cheuk‐Chun Szeto, Jack J. Lee, Ling Qin, Lai‐Shan Tam
Journal: Arthritis & Rheumatology (2025)

Objectives This study aimed to ascertain the effect of secukinumab on erosion and enthesiophyte progression in psoriatic arthritis (PsA) by high‐resolution peripheral quantitative computed tomography (HR‐pQCT). Methods This was a phase 4, double‐blind, randomized, placebo‐controlled trial. Patients with active PsA and ≥ 1 erosion in the metacarpophalangeal joints (MCPJ) 2‐4 were randomised in a 1:1 ratio to subcutaneous secukinumab or placebo. HR‐pQCT of the MCPJ 2‐4 were performed at baseline, week 24 and week 48 The primary outcome was the changes in the volume of erosions on MCPJ 2‐4 measured by HR‐pQCT at 24 and 48 weeks. Results Forty patients (age: 51.9±13.4 years, 20 [50%] male, disease duration: 4.7±6.7years) were recruited. Thirty‐four patients who completed study treatment were included in the per‐protocol analysis. At baseline, week 24 and week 48, the secukinumab group showed a significant reduction in erosion volume, whereas no changes were observed in the placebo group (change in the secukinumab group: ‐0.1 (‐0.5, 0.0) vs: 0.0 (‐0.2, 0.4) in the placebo group, p=0.004). A similar trend was observed for enthesiophyte volume changes in the secukinumab group, while no differences were noted in the placebo group (change in the secukinumab group: ‐0.1 (‐0.8, 0.0) vs 0.0 (‐0.4, 1.3) in the placebo group, p=0.067). GEE results showed that the odds ratio (OR) for enthesiophyte progression in the secukinumab group was 0.264 (95% CI: 0.080‐0.878, p=0.030), while the OR for partial erosion healing in the secukinumab group was 2.882 (95% CI: 1.130 to 7.349, p=0.027). Conclusions Secukinumab demonstrates a potential benefit in facilitating partial erosion repair and preventing enthesiophyte progression in PsA. image
Designing clinical trials for the treatment of membranous nephropathy in the anti-PLA2R era: results of a Nephcure membranous nephropathy workshop
Authors: Marco Prunotto, Patrick H Nachman, Barbara S Gillespie, Laurence H Beck, Aliza M Thompson, Austin H Hu, Elizabeth A Stafford, Josh M Tarnoff, Brad H Rovin
Journal: Kidney International (2025)

Primary membranous nephropathy is a common cause of adult-onset nephrotic syndrome, with an overall incidence of 12 cases per million per year. Primary membranous nephropathy is an autoimmune kidney disease; however, primary membranous nephropathy autoantigens remained elusive until 2009 when the M-type phospholipase A2 receptor 1 (PLA2R) was identified as a disease autoantigen. This was followed relatively rapidly by identification of several other autoantigens. Autoantibodies against PLA2R are detectable in ≈75% of patients with primary membranous nephropathy. The discovery of circulating and deposited autoantibodies against PLA2R offers an opportunity in nephrology to personalize disease management. On January 14, 2023, Nephcure Kidney International convened a scientific workshop in Arlington, Virginia, to discuss the state of the science on autoantibodies against PLA2R and considerations related to the incorporation of autoantibodies against PLA2R in drug development programs for membranous nephropathy. The present report captures the discussion that occurred at the Membranous Nephropathy Scientific Workshop.
Dual Inhibition of MAPK and TORC1 Signaling Retards Development of Radiation Resistance in Pediatric <i>BRAF</i> <i>V600E</i> Glioma Models
Authors: Fuyang Li, Kathryn M Bondra, Hanzhou Wang, Dias Kurmashev, Bipasha Mukherjee, Suman Kanji, Amyn A Habib, Yidong Chen, Siyuan Zheng, Sandeep Burma, Peter J Houghton
Journal: Neuro-Oncology (2025)

Abstract Background MAPK pathway inhibitors (MAPKi) have shown significant efficacy in treating childhood BRAF-activated brain tumors. For tumors harboring BRAFV600E mutations, the drugs are rarely curative, and patients can become refractory to treatment. MAPKi combining X-radiation therapy (XRT) may improve cure rate, but development of XRT-resistance is a challenge. Methods XRT-resistance was induced by multiple XRT cycles in pediatric BRAFV600E glioma patient-derived xenograft (PDX) models. RNA sequencing was performed to identify differentially expressed genes and pathways potentially contributing to XRT-resistance. Cells isolated from PDXs were used to test the contribution of specific genes and pathways to XRT-resistance. PDX models were used to evaluate the efficacy of targeted treatments combined with XRT. Results Tumors developed resistance after multiple cycles of XRT. MEK inhibition combining XRT significantly improved tumor control, compared to XRT alone, but resistance to combined therapy developed rapidly. RNA-sequencing analysis revealed up-regulation of MAPK and PI3K-mTOR signaling in the XRT-resistant tumors. Isolated cells showed in vitro resistance to XRT, which was partially reversed by inhibiting PI3K-mTOR. Up-regulation of TORC1 signaling in XRT naïve tumor cells, via constitutively active AKT or TSC2 deletion, conferred in vitro XRT-resistance.The pro-survival gene BIRC5 (Survivin), a target of TORC1 signaling, contributed to XRT-resistance. Combining trametinib-rapamycin with XRT significantly enhanced therapeutic efficacy in PDX models and prevented or delayed resistance development. Conclusion PI3K-mTOR activation promotes the development of XRT-resistance in pediatric BRAFV600E glioma. Dual targeting of MAPK and TORC1 signaling significantly enhances the therapeutic efficacy of XRT, and can potentially prevent the development of XRT-resistance. (250 words)