tbuckley/cabot-search huggingface dataset:
Climatic drivers of infectious diarrheal disease epidemics in China: an empirical dynamic modeling analysis of 21 million cases
Authors: Jiayi Zhou, Yunchong Yao, Lingling Li, Xu Wang, Tingting Dai, Xiaoyan Cai, Lingxi Wang, Yueqin She, Xingxing Zhang, Jinhui Zhang, Haijian Zhou, Haisheng Wu, Pi Guo
Journal: Journal of Infection (2025)

Infectious diarrheal diseases continue to impose a heavy public health burden in China, despite significant advancements in sanitation and economic development. While existing evidence has linked climate factors to the dynamic of these diseases, the heterogeneous climatic conditions and complex nonlinear interactions among meteorological variables give rise to intricate epidemic patterns that complicate the identification of causal drivers underlying the observed spatial and temporal variability in disease incidence. To address this gap, we conducted a nationwide study across 365 city-level regions in China from 2005 to 2022. Based on high-resolution surveillance data and meteorological records, we applied an empirical dynamic modeling framework. We inferred causal links between climatic drivers and six notifiable infectious diarrheal diseases using convergent cross mapping, and further assessed the dynamic impacts of these drivers through multivariate forecast improvement and scenario exploration across different climatic zones. Our results reveal that, except for cholera, infectious diarrheal diseases are predominantly influenced by temperature, relative humidity, and sunshine-hour. Temperature generally promotes the incidence of typhoid fever, bacillary dysentery, and other infectious diarrhea, while the influence of relative humidity and sunshine-hour varies with environmental context. This study not only characterizes the epidemiological trends of infectious diarrhea over nearly two decades but also demonstrates the feasibility of using EDM to uncover dynamic nonlinear interactions in climate-disease systems. By integrating empirical dynamic modeling into public health frameworks, our approach provides a scalable and effective tool for disentangling complex climate-disease interactions in a warming world, thereby informing more tailored public health interventions in response to climate change.
A standardized framework for robust fragmentomic feature extraction from cell-free DNA sequencing data
Authors: Haichao Wang, Paulius D Mennea, Yu Kiu Elkie Chan, Zhao Cheng, Maria C Neofytou, Arif Anwer Surani, Aadhitthya Vijayaraghavan, Emma-Jane Ditter, Richard Bowers, Matthew D Eldridge, Dmitry S Shcherbo, Christopher G Smith, Florian Markowetz, Wendy N Cooper, Tommy Kaplan, Nitzan Rosenfeld, Hui Zhao
Journal: Genome biology (2025)

Abstract Fragmentomics features of cell-free DNA represent promising non-invasive biomarkers for cancer diagnosis. A lack of systematic evaluation of biases in feature quantification hinders the adoption of such applications. We compare features derived from whole-genome sequencing of ten healthy donors using nine library kits and ten data-processing routes and validated in 1182 plasma samples from published studies. Our results clarify the variations from library preparation and feature quantification methods. We design the Trim Align Pipeline and cfDNAPro R package as unified interfaces for data pre-processing, feature extraction, and visualization to standardize multi-modal feature engineering and integration for machine learning.
Successful treatment of pemphigus vulgaris with obinutuzumab
Authors: Colin Tang-Whitmore, Laureb Ostlund, Kati Munson, Brittney Schultz
Journal: British Journal of Dermatology (2025)

This letter highlights the successful use of obinutuzumab as an alternative therapy for a patient with pemphigus vulgaris who could not tolerate rituximab. Our findings suggest that obinutuzumab may offer a promising treatment option for patients with autoimmune skin diseases when first-line therapies fail.
Preclinical validation of PKC412 as a therapy candidate for epidermolysis bullosa simplex across multiple keratin pathogenic variants
Authors: Henriette Jopp, Alexander Kraft, Bernd Hoffmann, Rudolf Merkel, M Bishr Omary, Cristina Has, Thomas M Magin, Katrin Rietscher
Journal: British Journal of Dermatology (2025)

Abstract Background Epidermolysis bullosa simplex (EBS) is a hereditary skin fragility disorder caused by missense pathogenic variants in KRT5 or KRT14. These variants trigger the collapse of the cytoskeleton into cytoplasmic protein aggregates, which renders the epidermis highly susceptible to mechanical stress and leads to intraepidermal blistering and loss of intercellular cohesion. Currently, no molecular therapies for EBS exist. Objectives Characterization of K5 or K14 mutant keratinocytes, from patients with EBS, in response to PKC412 treatment in monolayer culture and in epidermal equivalents. This clarifies the potential of PKC412 as a drug repurposing therapy approach in EBS. Methods We conducted a comprehensive characterization of K5 and K14 mutant keratinocytes in response to PKC412, examining its effects on proliferation, wound closure, and apoptosis. Additionally, we evaluated the improvement of intercellular cohesion through stretch assays, epithelial sheet assays, and assessment of desmosomal organization. Finally, we investigated the efficacy of PKC412 application in both skin explants and EBS-derived epidermal equivalent cultures. Results We demonstrated that PKC412 is effective in various keratinocytes carrying pathogenic variants associated with localized, generalized, or intermediate forms of EBS. PKC412 enhanced intercellular adhesion in both immortalized normal and EBS keratinocytes, as well as normal primary keratinocytes, and under stretch conditions. Immunoblot analyses revealed a concentration-dependent reduction in desmoplakin phosphorylation, which remained stable over the course of three days at the sites investigated. Additionally, application of PKC412 in epidermal equivalent cultures restored desmoplakin distribution in the epidermal basal layer. Conclusions PKC412 markedly enhanced intercellular cohesion and stress resilience in patient-derived EBS keratinocytes, both in monolayer and 3D culture systems. These findings highlight PKC412 as a promising therapeutic candidate for the treatment of EBS.
Adjusting the scope of natural killer cells in cancer therapy
Authors: Zihen Shen, Xiangpeng Meng, Jai Rautela, Michael Chopin, Nicholas D Huntington
Journal: Cellular and Molecular Immunology (2025)

Abstract Natural killer (NK) cells have evolved to detect abnormalities in tissues arising from infection with pathogens, genomic damage, or transformation and respond rapidly to the production of potent proinflammatory and cytolytic mediators. While this acute proinflammatory response is highly efficient at orchestrating sterilizing immunity to pathogens in a matter of days, cellular transformation often avoids the innate detection mechanisms of NK cells. When cellular transformation results in malignancy, tumor cells and/or the tumor microenvironment can evolve additional mechanisms to circumvent NK cell responses, and cancer is now a dominant disease burden worldwide. Here, we review recent advances in our understanding of the combined relationship between malignancies and natural killer (NK) cells, learn from recent clinical efforts in therapeutically targeting natural killer (NK) cells in cancer and outline some emerging therapeutic concepts that aim to improve the innate immune response against cancer.
β-hydroxybutyrate inhibits Plasmodium falciparum development and confers protection against malaria in mice
Authors: Zhiming Wei, Ning Jiang, Yiwei Zhang, Qilong Li, Ziwei Su, Yanxin Zhang, Kunying Lv, Yixin Yang, Tong Liu, Lu Sun, Kexin Zheng, Ang Li, Anni Feng, Xiaoyu Sang, Ying Feng, Ran Chen, Qijun Chen
Journal: Nature Metabolism (2025)

Environmental factors restrict malaria parasite development, but the influence of host metabolic variations on the infectivity of the blood stage parasite is not fully understood. Here we show that mice on a ketogenic diet are completely protected from infection with the malaria parasite Plasmodium berghei. We further show that administration of the ketone body β-hydroxybutyrate (βOHB), but not of acetoacetate, increases survival of infected mice and inhibits proliferation of both P. berghei and Plasmodium falciparum in vitro. Administration of either a ketogenic diet or βOHB induces metabolic reprogramming in parasites, including reduced levels of nicotinamide adenine dinucleotide, which is associated with the downregulation of genes controlling parasite development, erythrocyte invasion and pathogenicity. Our data indicate that a ketogenic diet and the ketone body βOHB confer resistance to malaria in mice by causing developmental arrest of Plasmodium parasites, highlighting the potential of dietary and metabolic strategies to fight malarial infection.
Tension-induced directional migration of hepatic stellate cells potentially coordinates liver fibrosis progression
Authors: Lyu Zhou, Ziao Shi, Xuesi Yang, Jia'nan Zeng, Zhifeng You, Yuying Zhang, Zhiyue Zhu, Zhiqiang Liu, Yudi Niu, Hongsheng Yu, Jinliang He, Yi Long, Zhaozhao Wu, Yan Zhang, Cheng Lyu, Liping Deng, Yuan Wang, Congying Wu, Yanan Du
Journal: Nature Biomedical Engineering (2025)
Aberrant engagement of P-selectin drives hematopoietic stem cell aging in mice
Authors: Daozheng Yang, Natalia Skinder, Yun-Ruei Kao, Jiahao Chen, Victor Thiruthuvanathan, Arthur Flohr Svendsen, Chi Zhang, Bertien Dethmers-Ausema, Ellen Weersing, Maria Maryanovich, Britta Will, Gerald de Haan
Journal: Nature Aging (2025)
Impact of Conditioning Intensity on Clinical Outcomes of Second Allogeneic Hematopoietic Cell Transplantation for Relapse After First Transplantation
Authors: Kazuki Yoshimura, Hideki Nakasone, Masaharu Tamaki, Hiroki Hosoi, Kazuaki Kameda, Naoyuki Uchida, Noriko Doki, Takahiro Fukuda, Satoshi Yoshihara, Yasuo Mori, Hirohisa Nakamae, Masatsugu Tanaka, Yuta Katayama, Tetsuya Eto, Yuta Hasegawa, Shuichi Ota, Satoshi Takahashi, Makoto Yoshimitsu, Fumihiko Ishimaru, Junya Kanda, Yoshiko Atsuta, Kimikazu Yakushijin
Journal: American Journal of Hematology (2025)

ABSTRACT Although second allogeneic hematopoietic cell transplantation HCT (HCT2) is a potentially curative treatment for patients relapsing after their first HCT (HCT1), it is associated with higher non‐relapse mortality (NRM) compared with HCT1. Furthermore, while reduced‐intensity conditioning (RIC) in HCT2 might decrease NRM, there is no consensus on which patients may benefit from RIC. We retrospectively analyzed 2478 patients who underwent HCT2 for relapse of hematologic malignancies after HCT1. In a multivariate analysis, older recipient age, short duration between HCT1 and HCT2, RIC in HCT1, HCT‐CI ≥ 2, and ECOG PS ≥ 2 were associated with an increased risk of NRM. RIC in HCT2 was associated with better NRM compared to myeloablative conditioning (MAC) (hazard ratio [HR] 0.83, 95% confidence interval [CI]: 0.72–0.97; p = 0.018), but was not significantly associated with overall survival (OS) (HR 0.91, 95% CI: 0.82–1.01; p = 0.075). We observed a significant interaction for NRM between extensive cGVHD in HCT1 and the conditioning intensity of HCT2 (interaction p &lt; 0.001), meaning that the benefit of RIC in HCT2 was seen in patients with extensive cGVHD in HCT1, but not in those without cGVHD. RIC in HCT2 was also associated with superior OS in patients with extensive cGVHD in HCT1 (HR 0.68, 95% CI: 0.49–0.93; p = 0.02), with significant interaction between the conditioning intensity and the prior history of extensive cGVHD (interaction p = 0.01). This study suggests that RIC in HCT2 reduces NRM for HCT2 and improves OS, especially in patients with a history of extensive cGVHD.
Loss of SMARCA4 leads to Intron Retention and Generation of Tumor-Associated Antigens in Small Cell Carcinoma of the Ovary, Hypercalcemic Type
Authors: Elizabeth A. Raupach, Apurva M. Hegde, Krystine Garcia-Mansfield, Marice Alcantara, David L. Rose, Rebecca F. Halperin, Krystal A. Orlando, Jessica D. Lang, Ritin Sharma, Victoria David-Dirgo, Salvatore J. Facista, Rayvon Moore, Rochelle Kofman, Zoe N. Jensen, Victoria L. Zismann, Anthony N. Karnezis, Yemin Wang, Lynda B. Bennett, Timothy G. Whitsett, Marcin Kortylewski, William P.D. Hendricks, David Huntsman, Lorna Rodriguez-Rodriguez, Bernard E. Weissman, Jeffrey M. Trent, Patrick Pirrotte
Journal: Cancer Research (2025)

Abstract Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare, deadly form of ovarian cancer that uniformly harbors mutations in SMARCA4, a member of the SWI/SNF chromatin remodeling complex. SWI/SNF impacts RNA splicing, and dysregulation of splicing can generate immunogenic tumor antigens. Here, we explored the relationship between SMARCA4 loss and RNA splicing dysregulation. SCCOHT primary tumors harbored tumor-associated outlier splicing events compared to normal tissues. Many of the tumor events were retained introns encoding novel peptides predicted to bind to MHC-I complexes. Immune cells were observed in primary SCCOHT tumors, suggesting a potentially immune reactive tumor microenvironment. Mutations in several SWI/SNF subunits were associated with higher rates of outlier retained introns across tumor types in TCGA data. Interestingly, RNA sequencing of isogenic SCCOHT cell lines demonstrated a role for SMARCA4 in intron retention. Distinct protein-protein interactions between splicing factors identified in SCCOHT cell lines supported a role for SMARCA4 in splicing regulation. Further, SWI/SNF localized to genes which were differentially spliced. Mass spectrometry analyses confirmed expression of some of these novel peptides and a subset of these are predicted to bind to MHC-I complexes. A pool of these novel peptides derived from retained introns in SCCOHT triggered proliferation and expression of TNFa and INFb in primary human T cells. Together, these data suggest that SMARCA4 loss in SCCOHT leads to intron retention. Furthermore, T cell activation by novel peptides encoded by these tumor-specific splicing events suggests intron retention could be a source of tumor-associated antigens in SCCOHT.
DDX5 super-enhancer promotes vasculogenic mimicry formation and metastasis in nasopharyngeal carcinoma by enhancing ADAM10 transcription
Authors: Tian Xia, Haimeng Yin, Qingwen Zhu, Kaiwen Zhang, Haijing Xie, Ying Shan, Siyu Zhang, Rui Zhu, Keying Li, Mengyu Miao, Yingna Lu, Zhefang Wang, Jianmei Zhao, Yiwen You, Bo You
Journal: Cell Reports Medicine (2025)

Anti-angiogenic therapies (AATs) exhibit limited efficacy, as most patients with cancer inevitably develop resistance to them. In this study, data generated using a nasopharyngeal carcinoma orthotopic mouse model, combined with clinical data, reveal compensatory vasculogenic mimicry (VM) formation during AAT treatment and the association of VM with poor prognosis in nasopharyngeal carcinoma. Additionally, data-independent acquisition mass spectrometry-based proteomics shows that upregulation of a disintegrin And metalloprotease 10 (ADAM10) contributes to VM. Mechanistically, epigenetic and high-resolution chromatin interaction landscape analyses demonstrate that although ADAM10 does not interact with either the proximal or distal enhancers, DEAD-box helicase 5 (DDX5), a transcription factor of ADAM10, is regulated by long-range looping enhancer-promoter interactions. Further analyses identify transcription factors binding to critical constituents of the DDX5 super-enhancer. Ingenol mebutate, which docks excellently with DDX5, reverses ADAM10-mediated gene expression changes, thereby effectively suppressing compensatory VM formation and metastasis and improving prognosis. Collectively, these findings provide insights into the clinical application of AATs.
Minimally invasive diagnosis of precancerous cervical lesions using single-cell peripheral immune atlas
Authors: Junfen Xu, Qinghua Ji, Quanming Kong, Lijuan Lv, Bo Zhu, Xiufeng Huang, Zhengyun Chen, Ping Xu, Xiao Li, Weiwei Yin, Hui Wang
Journal: Cell Reports Medicine (2025)

Cervical cancer remains a major global health concern for women. Current screening methods are either invasive or lead to low participation and over-referral for colposcopy, particularly among high-risk human papillomavirus (HPV)-positive women. This study analyzes 613 participants with varying cervical lesions using mass cytometry by time-of-flight (CyTOF) to identify disease-specific peripheral immune signatures. A diagnostic model based on 23 immune features achieves ∼91% sensitivity and specificity for detecting precancerous and cancerous lesions. A separate model for HPV-positive women shows even higher accuracy (∼93% sensitivity, ∼95% specificity), especially in HPV16/18-positive cases (99% sensitivity, 100% specificity). In an independent validation cohort (n = 105), the model distinguishes cervical intraepithelial neoplasia (CIN) 2+ from ≤CIN1 with 86.5% sensitivity and 85.3% specificity (area under the curve [AUC] = 0.89). These findings support peripheral immune profiling as a minimally invasive and accurate biomarker strategy for early cervical cancer screening, particularly in HPV16/18-positive women.
Single-cell profiling of bone metastasis ecosystems from multiple cancer types reveals convergent and divergent mechanisms of bone colonization
Authors: Fengshuo Liu, Yunfeng Ding, Zhan Xu, Xiaoxin Hao, Tianhong Pan, George Miles, Siyue Wang, Yi-Hsuan Wu, Jun Liu, Igor L Bado, Weijie Zhang, Ling Wu, Yang Gao, Liqun Yu, David G Edwards, Hilda L Chan, Sergio Aguirre, Michael Warren Dieffenbach, Elina Chen, Yichao Shen, Dane Hoffman, Luis Becerra Dominguez, Charlotte Helena Rivas, Xiang Chen, Hai Wang, Zbigniew Gugala, Robert L Satcher, Xiang H-F Zhang
Journal: Cell Genomics (2025)

Bone is a common site for metastasis of solid cancers. The diversity of histological and molecular characteristics of bone metastases (BMs) remains poorly studied. Here, we performed single-cell RNA sequencing on 42 BMs from eight cancer types, identifying three distinct ecosystem archetypes, each characterized by an enrichment of specific immune cells: macrophages/osteoclasts, regulatory/exhausted T cells, or monocytes. We validated these archetypes by immunostaining on tissue sections and bioinformatic analysis of bulk RNA sequencing/microarray data from 158 BMs across more than 10 cancer types. Interestingly, we found only a modest correlation between the BM archetypes and the tissues of origin; BMs from the same cancer type often fell into different archetypes, while BMs from different cancer types sometimes converged on the same archetype. Additional analyses revealed parallel immunosuppression and bone remodeling mechanisms, some of which were experimentally validated. Overall, we discovered unappreciated heterogeneity of BMs across different cancers.
Multimodal fusion model for prognostic prediction and radiotherapy response assessment in head and neck squamous cell carcinoma
Authors: Ruxian Tian, Feng Hou, Haicheng Zhang, Guohua Yu, Ping Yang, Jiaxuan Li, Ting Yuan, Xi Chen, Ying Chen, Yan Hao, Yisong Yao, Hongfei Zhao, Pengyi Yu, Han Fang, Liling Song, Anning Li, Zhonglu Liu, Huaiqing Lv, Dexin Yu, Hongxia Cheng, Ning Mao, Xicheng Song
Journal: npj Digital Medicine (2025)

Accurate prediction of prognosis and postoperative radiotherapy response is critical for personalized treatment in head and neck squamous cell carcinoma (HNSCC). We developed a multimodal deep learning model (MDLM) integrating computed tomography, whole-slide images, and clinical features from 1087 HNSCC patients across multiple centers. The MDLM exhibited good performance in predicting overall survival (OS) and disease-free survival in external test cohorts. Additionally, the MDLM outperformed unimodal models. Patients with a high-risk score who underwent postoperative radiotherapy exhibited prolonged OS compared to those who did not (P = 0.016), whereas no significant improvement in OS was observed among patients with a low-risk score (P = 0.898). Biological exploration indicated that the model may be related to changes in the cytochrome P450 metabolic pathway, tumor microenvironment, and myeloid-derived cell subpopulations. Overall, the MDLM effectively predicts prognosis and postoperative radiotherapy response, offering a promising tool for personalized HNSCC therapy.
Relative Age in School and Initiation of Speech Therapy in Children
Authors: Sophie Billioti de Gage, Hugo Peyre, Martin Chalumeau, Yann Mikaeloff, Mahmoud Zureik, Alain Weill
Journal: JAMA Network Open (2025)

Importance In most countries, children in the same grade can be up to 12 months apart in age, which represents a considerable relative age difference, particularly in the early years. A relative age effect has been frequently reported in the diagnosis and treatment of attention-deficit/hyperactivity disorder and, more rarely, in the diagnosis of other neurodevelopmental disorders. The relative age effect has never been studied for speech therapy, which is frequently prescribed to treat specific language and learning disorders. Objective To quantify the association of relative age with the initiation of speech therapy. Design, Setting, and Participants This cohort study used data from the French National Health Data System and included all children born in France between 2010 and 2016 from September of the year of their 5th birthday until July of the year of their 10th birthday or July 31, 2022 (end of study). Exposure Children were categorized according to month of birth. Main Outcomes and Measures Risk of speech therapy initiation was estimated using Cox models adjusted for other known risk factors. Results In total, 4 188 985 children (mean [SD] age, 5.2 [0.3] years; 50.8% girls) were included. Speech therapy was initiated for 692 086 children (incidence rate, 53.1 per 1000 person-years, 54.5% boys) during a mean (SD) follow-up of 3.1 (1.6) years. Among children of the same schooling level, the risk of initiating speech therapy steadily increased according to quarter and month of birth, with adjusted hazard ratios of 1.51 (95% CI, 1.50-1.52) for children born in the last quarter vs the first quarter and 1.64 (95% CI, 1.62-1.66) for children born in December vs those born in January. The relative age effect observed for speech therapy was of the same magnitude as that observed for methylphenidate in attention-deficit/hyperactivity disorder (positive control outcome). No relative age effect was observed for the initiation of desmopressin for nocturnal enuresis (negative control outcome). Conclusions and Relevance This cohort study found that among children in the same grade, an age difference of a few months was associated with the frequency of initiation of speech therapy. These findings may be attributable to a mismatch between the expectations of the school system and the relative age and level of maturity of the children or earlier identification of neurodevelopmental disorders in the youngest children in each age group.