tbuckley/cabot-search huggingface dataset:
The Role of <scp>WNT5a</scp> and <scp>TGF</scp>‐β1 in Airway Remodelling and Severe Asthma
Authors: Tariq Daud, Sheree Roberts, Nazanin Zounemat Kermani, Matthew Richardson, Liam G. Heaney, Ian M. Adcock, Yassine Amrani, Peter Bradding, Salman Siddiqui
Journal: Allergy (2025)

ABSTRACT Background Airway remodelling is a feature of severe asthma with airway epithelial damage observed frequently. We evaluated the role of WNT5a and TGF‐β 1 in asthmatic airway biopsies and in sputum and bronchial brushings assessed their role in remodelling. Methods WNT5a and TGF‐β 1 protein expression were assessed in the lamina propria epithelium of people with asthma (GINA 1–3, n‐8 and GINA 4–5, n‐14) and healthy subjects (n‐9), alongside relevant remodelling markers. The effects of WNT5a and TGF‐β 1 on BEAS‐2B epithelial cell wound healing and differentiation were assessed in vitro. Replication was performed in the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U‐BIOPRED) study in sputum ( n = 120) and bronchial brushes ( n = 147). Results WNT5a and TGF‐β 1 protein expression were significantly increased in the airway epithelium and lamina propria in asthma patients with concurrent airflow limitation or severe disease. Furthermore, WNT5a protein expression in the lamina propria correlated with tissue eosinophils and vascular remodelling. Airway epithelial WNT5a was co‐localised predominantly to airway basal cells and correlated with Th17 gene expression ( r = 0.40, p = 0.025) and both the % intact ( r s = 0.54, p = 0.001) and % denuded epithelium ( r s = −0.39, p = 0.003). Experiments in BEAS‐2B cells confirmed that WNT5a at maximal physiological concentrations (1 μg/mL), promoted epithelial wound healing, independently of TGF‐β 1 , as well as induction of EMT‐like morphology. WNT5a mRNA was associated with severe asthma, airflow limitation, sputum eosinophilia and Th2, and Th17 and neutrophil activation transcriptomes in sputum in U‐BIOPRED. Conclusion WNT5a is associated with both airway remodelling and severe asthma. Trial Registration ClinicalTrials.gov identifier: NCT01982162
NUFIP1 integrates amino acid sensing and DNA damage response to maintain the intestinal homeostasis
Authors: Hui Ming, Jing Tan, Si-Yi Cao, Cheng-Ping Yu, Yu-Ting Qi, Chao Wang, Lei Zhang, Ying Liu, Jian Yuan, Miao Yin, Qun-Ying Lei
Journal: Nature Metabolism (2025)
Personalized, autologous neoantigen-specific T cell therapy in metastatic melanoma: a phase 1 trial
Authors: Jessica S. W. Borgers, Divya Lenkala, Victoria Kohler, Emily K. Jackson, Matthijs D. Linssen, Sebastian Hymson, Brian McCarthy, Elizabeth O’Reilly Cosgrove, Kristen N. Balogh, Ekaterina Esaulova, Kimberly Starr, Yvonne Ware, Sebastian Klobuch, Tracey Sciuto, Xi Chen, Gauri Mahimkar, Joong Hyuk F. Sheen, Suchitra Ramesh, Sofie Wilgenhof, Johannes V. van Thienen, Karina C. Scheiner, Inge Jedema, Michael Rooney, Jesse Z. Dong, John R. Srouji, Vikram R. Juneja, Christina M. Arieta, Bastiaan Nuijen, Claudia Gottstein, Olivia C. Finney, Kelledy Manson, Cynthia M. Nijenhuis, Richard B. Gaynor, Mark DeMario, John B. Haanen, Marit M. van Buuren
Journal: Nature Medicine (2025)
Resurgence of malaria and artemisinin resistance in Africa requires a concerted response
Authors: Nebiyu Dereje, Mosoka Papa Fallah, Tamrat Shaweno, Alemayehu Duga, Mazyanga Lucy Mazaba, Tajudeen Raji, Morenike O. Folayan, Ngashi Ngongo, Nicaise Ndembi, Jean Kaseya
Journal: Nature Medicine (2025)
Comprehensive genomic characterization of early-stage bladder cancer
Authors: Frederik Prip, Philippe Lamy, Sia Viborg Lindskrog, Trine Strandgaard, Iver Nordentoft, Karin Birkenkamp-Demtröder, Nicolai Juul Birkbak, Nanna Kristjánsdóttir, Asbjørn Kjær, Tine G. Andreasen, Johanne Ahrenfeldt, Jakob Skou Pedersen, Asta Mannstaedt Rasmussen, Gregers G. Hermann, Karin Mogensen, Astrid C. Petersen, Arndt Hartmann, Marc-Oliver Grimm, Marcus Horstmann, Roman Nawroth, Ulrika Segersten, Danijel Sikic, Kim E. M. van Kessel, Ellen C. Zwarthoff, Tobias Maurer, Tatjana Simic, Per-Uno Malmström, Núria Malats, Jørgen Bjerggaard Jensen, Kim E. M. van Kessel, Francisco X. Real, Lars Dyrskjøt
Journal: Nature Genetics (2025)
Analysis of multi-condition single-cell data with latent embedding multivariate regression
Authors: Constantin Ahlmann-Eltze, Wolfgang Huber
Journal: Nature Genetics (2025)

Abstract Identifying gene expression differences in heterogeneous tissues across conditions is a fundamental biological task, enabled by multi-condition single-cell RNA sequencing (RNA-seq). Current data analysis approaches divide the constituent cells into clusters meant to represent cell types, but such discrete categorization tends to be an unsatisfactory model of the underlying biology. Here, we introduce latent embedding multivariate regression (LEMUR), a model that operates without, or before, commitment to discrete categorization. LEMUR (1) integrates data from different conditions, (2) predicts each cell’s gene expression changes as a function of the conditions and its position in latent space and (3) for each gene, identifies a compact neighborhood of cells with consistent differential expression. We apply LEMUR to cancer, zebrafish development and spatial gradients in Alzheimer’s disease, demonstrating its broad applicability.
Refining breast cancer genetic risk and biology through multi-ancestry fine-mapping analyses of 192 risk regions
Authors: Guochong Jia, Zhishan Chen, Jie Ping, Qiuyin Cai, Ran Tao, Chao Li, Joshua A. Bauer, Yuhan Xie, Stefan Ambs, Mollie E. Barnard, Yu Chen, Ji-Yeob Choi, Yu-Tang Gao, Montserrat Garcia-Closas, Jian Gu, Jennifer J. Hu, Motoki Iwasaki, Esther M. John, Sun-Seog Kweon, Christopher I. Li, Koichi Matsuda, Keitaro Matsuo, Katherine L. Nathanson, Barbara Nemesure, Olufunmilayo I. Olopade, Tuya Pal, Sue K. Park, Boyoung Park, Michael F. Press, Maureen Sanderson, Dale P. Sandler, Chen-Yang Shen, Melissa A. Troester, Song Yao, Ying Zheng, Thomas Ahearn, Abenaa M. Brewster, Adeyinka Falusi, Anselm J. M. Hennis, Hidemi Ito, Michiaki Kubo, Eun-Sook Lee, Timothy Makumbi, Paul Ndom, Dong-Young Noh, Katie M. O’Brien, Oladosu Ojengbede, Andrew F. Olshan, Min-Ho Park, Sonya Reid, Taiki Yamaji, Gary Zirpoli, Ebonee N. Butler, Maosheng Huang, Siew-Kee Low, John Obafunwa, Clarice R. Weinberg, Haoyu Zhang, Hongyu Zhao, Michelle L. Cote, Christine B. Ambrosone, Dezheng Huo, Bingshan Li, Daehee Kang, Julie R. Palmer, Xiao-Ou Shu, Christopher A. Haiman, Xingyi Guo, Jirong Long, Wei Zheng
Journal: Nature Genetics (2025)
Updated analysis of EMN02 demonstrated overall survival benefit to early ASCT for multiple myeloma
Authors: Alfred L. Garfall
Journal: Blood Cancer Journal (2025)

Pawlyn et al. offer a thoughtful recent commentary in BloodCancer Journal on progression-free survival (PFS) as a surrogate endpoint for overall survival (OS) in multiple myeloma trials [1].In the section discussing "the issue of competing risks," authors discuss trials of autologous stem cell transplantation (ASCT).The authors write, "Prior studies of transplant have shown consistent PFS with ASCT, but OS benefit has been less clear."In support of this point, the authors write that the EMN02 study, which compared post-induction intensification with autologous stem cell transplant (ASCT) to bortezomib-melphalan-prednisone (VMP), demonstrated PFS benefit with ASCT but "no significant difference in OS." Authors cite the primary analysis of EMN02, which was published in June 2020 with median follow-up of 60.3 months [2].Longer follow-up of EMN02, however, did demonstrate a significant OS benefit with early ASCT after median follow-up of 75 months, as reported at the 2020 ASH Annual Meeting, with a hazard ratio of 0.81 (95% CI 0.66-0.98,p = 0.034) [3].The OS benefit with front-line ASCT in EMN02 is notable considering the substantial (63%) crossover to ASCT in later line therapy.EMN02 results therefore support an OS benefit to ASCT and a relationship between PFS and OS in ASCT trials.
The structural violence of cisgender norms: a participatory qualitative study of access to health and social welfare for older transgender women in Indonesia
Authors: Alegra Wolter, Benjamin Hegarty, Ika Susetyo, Lenny Sugiharto, Rully Mallay, Jaclyn Kaunang, Aditya Wardhana
Journal: International Journal of Transgender Health (2025)

Background Transgender women commonly experience poor health outcomes. However, little is known about older transgender women's experiences of government healthcare and social welfare programs in low and middle-income countries, in the context of discrimination and neglect.
Understanding sustainable return to work during gender transition, a (mixed method) diary-based single-case study of a transgender woman: spiegel im spiegel
Authors: Joy Van de Cauter, Joz Motmans, Dominique Van de Velde, Lutgart Braeckman
Journal: International Journal of Transgender Health (2025)

Background Psychosocial obstacles have been recognized as a significant factor in the return to work (RTW) for cisgender individuals with various health issues. RTW and sustained work participation of transgender and gender diverse (TGD) people during socio-medical transition have been sparsely investigated. Transgender women face multifaceted challenges in the workplace, in life, in social relations, and regarding their gender-affirming healthcare.
Coacervate‐Derived Assembly of Poly(ethylene glycol) Nanoparticles for Combinational Tumor Therapy
Authors: Hanru Liu, Dandan Ren, Huimin Geng, Yuan Tian, Mengqi Li, Ning Wang, Shiling Yuan, Jingcheng Hao, Jiwei Cui
Journal: Advanced Healthcare Materials (2025)

Coacervates have garnered significant attention as potential drug carriers. However, the instability resulting from their intrinsic membrane-free nature restricts the application of coacervates in drug delivery. Herein, the engineering of poly(ethylene glycol) nanoparticles (PEG NPs) is reported using coacervates composed of PEG and polyphenols as the templates, where PEG is subsequently cross-linked based on different chemistries (e.g., thiol-disulfide exchange, click chemistry, and Schiff base reaction). The reported assembly strategy avoids the template removal process and the resultant PEG NPs exhibit excellent stability in the physiological environment compared to coacervates. The presence of polyphenols in PEG NPs enables the loading of various cargos including metal ions (i.e., Ru, Gd, Mn, Fe) and drug molecules (i.e., doxorubicin), which demonstrates their promise in magnetic resonance imaging and combinational tumor therapy. This work provides a promising strategy to promote the development of coacervate-derived NPs as a drug delivery system for biomedical applications.
Microbial DNA Profiles of Bacterial Extracellular Vesicles from 3D Salivary Polymicrobial Biofilms – A Pilot Study
Authors: Chun Liu, Nadeeka S. Udawatte, Andrew Liaw, Reuben Staples, Carlos Salomon, Chaminda Jayampath Seneviratne, Sašo Ivanovski, Pingping Han
Journal: Advanced Healthcare Materials (2025)

Abstract With the advent of multi‐layered and 3D scaffolds, the understanding of microbiome composition and pathogenic mechanisms within polymicrobial biofilms is continuously evolving. A fundamental component in mediating the microenvironment and bacterial‐host communication within the biofilm are bilayered nanoparticles secreted by bacteria, known as bacterial extracellular vesicles (BEVs), which transport key biomolecules including proteins, nucleic acids, and metabolites. Their characteristics and microbiome profiles are yet to be explored in the context of in vitro salivary polymicrobial biofilm. This pilot study aimed to compare the profiles of BEVs from salivary biofilm cultured on a 2D tissue culture plate and 3D melt electrowritten medical‐grade polycaprolactone (MEW mPCL) scaffold. BEVs derived from MEW mPCL biofilm exhibited enhanced purity and yield without altered EV morphology and lipopolysaccharide (LPS) content, with enriched BEVs‐associated DNA from Capnocytophaga, porphyromonas, and veillonella genus. Moreover, compared to saliva controls, MEW mPCL BEVs showed comparable DNA expression of Tannerella forsythia , and Treponema denticola and significantly higher expression in Porphyromonas gingivalis, Eikenella corrodens and Lactobacillus acidophilus . Together, these findings highlight a more detailed microbial profile with BEVs derived from salivary biofilms cultured on 3D MEW PCL scaffolds, which facilitates an effective in vitro model with a greater resemblance to naturally occurring biofilms.
Nonviral targeted mRNA delivery: principles, progresses, and challenges
Authors: Xi He, Guohong Li, Letao Huang, Haixing Shi, Sha Zhong, Siyu Zhao, Xiangyu Jiao, Jinxiu Xin, Xiaoling Yin, Shengbin Liu, Zhongshan He, Mengran Guo, Chunli Yang, Zhaohui Jin, Jun Guo, Xiangrong Song
Journal: MedComm (2025)

Abstract Messenger RNA (mRNA) therapeutics have garnered considerable attention due to their remarkable efficacy in the treatment of various diseases. The COVID‐19 mRNA vaccine and RSV mRNA vaccine have been approved on the market. Due to the inherent nuclease‐instability and negative charge of mRNA, delivery systems are developed to protect the mRNA from degradation and facilitate its crossing cell membrane to express functional proteins or peptides in the cytoplasm. However, the deficiency in transfection efficiency and targeted biological distribution are still the major challenges for the mRNA delivery systems. In this review, we first described the physiological barriers in the process of mRNA delivery and then discussed the design approach and recent advances in mRNA delivery systems with an emphasis on their tissue/cell‐targeted abilities. Finally, we pointed out the existing challenges and future directions with deep insights into the design of efficient mRNA delivery systems. We believe that a high‐precision targeted delivery system can greatly improve the therapeutic effects and bio‐safety of mRNA therapeutics and accelerate their clinical transformations. This review may provide a new direction for the design of mRNA delivery systems and serve as a useful guide for researchers who are looking for a suitable mRNA delivery system.
A SARS‐CoV‐2 EG.5 mRNA vaccine induces a broad‐spectrum immune response in mice
Authors: Hongyu Wang, Qinhua Peng, Xinxian Dai, Zhifang Ying, Xiaohong Wu, Xinyu Liu, Hongshan Xu, Jia Li, Leitai Shi, Jingjing Liu, Yunpeng Wang, Danhua Zhao, Yanqiu Huang, Lihong Yang, Ren Yang, Guangzhi Yue, Yue Suo, Qiang Ye, Shouchun Cao, Yuhua Li
Journal: MedComm (2025)

Abstract The emerging of emergent SARS‐CoV‐2 subvariants has reduced the protective efficacy of COVID‐19 vaccines. Therefore, novel COVID‐19 vaccines targeting these emergent variants are needed. We designed and prepared CoV072, an mRNA‐based vaccine against SARS‐CoV‐2 Omicron (EG.5) and other emergent SARS‐CoV‐2 subvariants that encodes the EG.5 spike protein. Six‐week‐old female BALB/C mice were used to assess humoral and cellular immune responses and cross‐reactive neutralizing activity against various SARS‐CoV‐2 subvariants. Meanwhile different immunization strategies and doses were performed to detect the immunogenicity of this mRNA vaccine. Our results show that two doses of 5 µg CoV072 or a single dose of 15 µg CoV072 both induced broad‐spectrum cross‐protection ability in mice. Compared with a single dose of 15 µg CoV072, two doses of 5 µg COV072 exhibited higher levels of pseudovirus neutralizing antibody (PNAb) and cross‐reactive IgG responses to multiple variants. Moreover, higher levels of neutralizing antibody (NAb) against live XBB and EG.5 variants were also induced. Th1‐biased cellular immune response was induced in all vaccination groups. The antigen design and immunization strategy of this study have reference significance for the research of the next generation of COVID‐19 vaccine and other vaccines.
Impaired network organization in mild age‐related hearing loss
Authors: Zhaopeng Tong, Chunhua Xing, Xiaomin Xu, Jin‐Jing Xu, Yuanqing Wu, Richard Salvi, Xindao Yin, Fei Zhao, Yu‐Chen Chen, Yuexin Cai
Journal: MedComm (2025)

Abstract Age‐related hearing loss (ARHL) is considered one of the most common neurodegenerative disorders in the elderly; however, how it contributes to cognitive decline is poorly understood. With resting‐state functional magnetic resonance imaging from 66 individuals with ARHL and 54 healthy controls, group spatial independent component analyses, sliding window analyses, graph‐theory methods, multilayer networks, and correlation analyses were used to identify ARHL‐induced disturbances in static and dynamic functional network connectivity (sFNC/dFNC), alterations in global network switching and their links to cognitive performances. ARHL was associated with decreased sFNC/dFNC within the default mode network (DMN) and increased sFNC/dFNC between the DMN and central executive, salience (SN), and visual networks. The variability in dFNC between the DMN and auditory network (AUN) and between the SN and AUN was decreased in ARHL. The individuals with ARHL had lower network switching rates than controls among global network nodes, especially in the DMN. Some disturbances within DMN were associated with disrupted executive and memory performance. The prolonged loss of sensory information associated with ARHL‐induced compensatory within‐network segregations and between‐network integrations in the DMN might reduce network information processing and accelerate brain aging and cognitive decline.
Left ventricular trabecular complexity for risk stratification of cancer therapy–related cardiac dysfunction in breast cancer
Authors: Hesong Shen, Qian Xu, Chunrong Tu, Yangling Peng, Yuhang Xie, Zhiming Miao, Rui Yang, Jiuquan Zhang
Journal: MedComm (2025)

Abstract The left ventricular trabecular fractal dimension (LVTFD) derived from cardiac magnetic resonance reflects myocardial trabecular complexity, which is associated with cardiovascular disease risk. Baseline risk stratification of cancer therapy–related cardiac dysfunction (CTRCD) in patients with breast cancer who received anthracycline is a very important clinical issue. In this study, we used the Cox model to derive and validate a new score system based on LVTFD for baseline risk stratification of CTRCD in breast cancer patients receiving anthracycline. We also compare the performance of LVTFD‐based score with the Heart Failure Association‐International Cardio‐Oncology Society (HFA‐ICOS) score using C‐index. This study enrolled 370 participants, of whom 73 participants developed CTRCD. The C‐indices of LVTFD‐based score integrating age, hypertension, previous cardiovascular disease, and maximal apical fractal dimension were higher than those of HFA‐ICOS score for stratifying CTRCD (0.834 vs. 0.642 and 0.834 vs. 0.633, respectively, in derivation and validation cohort). LVTFD‐based score can stratify the CTRCD risk, but HFA‐ICOS score cannot. The above results reveal that the LVTFD‐based score is an alternative method for baseline risk stratification of CTRCD in breast cancer who received anthracycline.
Authors' reply: Which dose regimen for glucocorticoid pulse therapy in patients with severe refractory RA?
Authors: F Buttgereit, G Burmester, J W Bijlsma, P Durez, A Nzeusseu Toukap, B R Lauwerys, D H Manicourt, J-P Devogelaer, F A Houssiau, P Verschueren, R Westhovens
Journal: Annals of the Rheumatic Diseases (2005)
Immune Regulation of Goblet Cell and Mucus Functions in Health and Disease
Authors: Jenny K. Gustafsson, Gunnar C. Hansson
Journal: Annual Review of Immunology (2025)

The mucosal surfaces of the body are the most vulnerable points for infection because they are lined by single or multiple layers of very active epithelial cells. The main protector of these cells is the mucus system generated by the specialized goblet cells secreting its main components, the gel-forming mucins. The organization of the mucus varies from an attached mucus that is impenetrable to bacteria in the large intestine to a nonattached, more penetrable mucus in the small intestine and airways. The respiratory tract mucus system clears particles and microorganisms from healthy lungs but causes disease if reorganized to an attached mucus that cannot be efficiently transported. Similarly, transformation of large intestine mucus from impenetrable to penetrable causes chronic inflammation directed toward the intestinal microbiota. Mucus-producing goblet cells are regulated by and responsive to signals from immune cells and at the same time signal back to the immune system. In this review we focus on the relationship of immune cells with intestinal goblet cells and mucus, making parallels to the respiratory tract.
Trends in Screening for Social Risk in US Physician Practices
Authors: Amanda L. Brewster, Hector P. Rodriguez, Genevra F. Murray, Valerie A. Lewis, Karen E. Schifferdecker, Elliott S. Fisher
Journal: JAMA Network Open (2025)

A wealth of research on screening for social risks in health care has emerged, but evidence is lacking on how social risk screening among physician practices has changed over time.
Mental Disorders Among Offspring Prenatally Exposed to Systemic Glucocorticoids
Authors: Kristina Laugesen, Nils Skajaa, Irene Petersen, Marianne Skovsager Andersen, Ulla Feldt-Rasmussen, Sofie Kejlberg Al-Mashhadi, Paul Stewart, Jens Otto Lunde Jørgensen, Henrik Toft Sørensen
Journal: JAMA Network Open (2025)

Current evidence of the association between prenatal exposure to glucocorticoids and long-term mental disorders is scarce and has limitations.
Digital Health Technology Research Funded by the National Institutes of Health
Authors: Pablo Cure, Thomas Radman, Jamie Mihoko Doyle, Audie A. Atienza, Joshua P. Fessel, Christopher M. Hartshorn
Journal: JAMA Network Open (2025)

Importance Digital health in biomedical research and its expanding list of potential clinical applications are rapidly evolving. A combination of new digital health technologies (DHTs), novel uses of existing DHTs through artificial intelligence– and machine learning–based algorithms, and improved integration and analysis of data from multiple sources has enabled broader use and delivery of these tools for research and health care purposes. The aim of this study was to assess the growth and overall trajectory of DHT funding through a National Institutes of Health (NIH)–wide grant portfolio analysis. Observations This study used 21 preselected DHT search terms to identify the funding allocations in DHT research across a 9-year period between fiscal year 2015 and fiscal year 2023. A subset of grants were manually curated to confirm the search terms’ accuracy and ascertain the stage of development, focus, and types of tools or approaches. To understand the translation of DHTs from biomedical research to clinical application, common measures, such as digital health publications and clinical trials were included. The DHT portfolio represented 2.8% (US $7 628 967 500) of the overall NIH grants funded from 2015 to 2023. DHT research funding increased during this period from $348 725 600 to $1 533 281 000. DHT research publications and clinical trials using the same search terms increased from 3714 to 14 786 and from 89 to 240, respectively. More DHT research funding was used for research and development purposes (59.3%) than for clinical or regulatory purposes (41.0%) based on manual, second-level data curation. Conclusions and Relevance This study found that investments in DHT research at the NIH has increased over the past 9 years and that this increase has been steady since 2015, including during and even after the COVID-19 pandemic. Increased use of DHTs is expected to continue as these technologies become a more integral part of the biomedical research ecosystem.