tbuckley/cabot-search huggingface dataset:
Rapid and Accurate Diagnosis of Urinary Tract Infections Using Targeted Next-Generation Sequencing: A Multicenter Comparative Study with Metagenomic Sequencing and Traditional Culture Methods
Authors: Zhenglin Chang, Jiwang Deng, Jinhu Zhang, Haojie Wu, Yuanyuan Wu, Lai Bin, Danmei Li, Jingxing Liu, Rixia Yu, Huaming Lin, Lingyue An, Baoqing Sun
Journal: Journal of Infection (2025)

BACKGROUNDUrinary tract infections (UTIs) rank among the most prevalent bacterial infections globally. Traditional urine culture methods have significant limitations in detection time and sensitivity, prompting the need to evaluate targeted next-generation sequencing (tNGS) as a potential diagnostic tool.METHODSThe study included a discovery cohort of 400 suspected UTI patients (202 analyzed) and a validation cohort of 200 patients (110 analyzed). The study assessed detection time, concordance rates, ability to identify polymicrobial infections, and antibiotic resistance genes (ARGs). Both clear and turbid urine samples were evaluated across different clinical settings.RESULTSIn the discovery cohort, tNGS demonstrated 96.5% concordance with culture-positive samples, while showing superior specificity in culture-negative specimens (53.1% vs 28.1% for mNGS). Detection time for tNGS (12.89h) was notably shorter than mNGS (17.38h) and traditional culture (61.48h). tNGS exhibited remarkable capability in identifying polymicrobial infections (55.4% of samples), significantly outperforming both mNGS (27.7%) and traditional culture methods, which failed to detect any co-infections. The method showed particular strength in detecting fastidious organisms like Ureaplasma parvum and fungal species such as Candida tropicalis. For antibiotic resistance prediction, tNGS detected more ARGs (52.67% vs 41.22% for mNGS) and achieved 100% sensitivity for vancomycin and methicillin resistance in Gram-positive pathogens. The validation cohort confirmed tNGS's robust performance, maintaining high concordance rates for both culture-positive (90.00%) and culture-negative samples (55.00%), demonstrating consistent reliability across different clinical settingsCONCLUSIONStNGS demonstrates advantages in rapid and accurate UTI diagnosis, particularly in detecting polymicrobial infections and analyzing antibiotic resistance genes. It shows promise as an effective complementary tool for UTI diagnostics.
Human dirofilariasis - a potentially significant nematode zoonosis in an era of climate change
Authors: Stefan Momčilović, Andriana Jovanović, Robin B. Gasser
Journal: Journal of Infection (2025)

Highlights•The clinical diagnosis of human dirofilariasis is challenging.•Nodules caused by dirofilariasis can occur in various body locations and tissues.•These nodules are often misdiagnosed as neoplasms.•Molecular tools can assist significantly in the diagnosis of human dirofilariasis.•Treatment is usually achieved by surgical excision of nodules.AbstractDirofilariasis is a mosquito-borne zoonosis caused by several species of the genus Dirofilaria. This disease can manifest as nodular lesions in subcutaneous tissues, various structures of the eye, the lungs and/or visceral organs. The Dirofilaria species and the vectors responsible for transmitting infection differ among various geographical regions. The most competent reservoirs of infection are domestic and wild canids (for Dirofilaria repens and Dirofilaria immitis), raccoons (for Dirofilaria tenuis) and bears (for Dirofilaria ursi), and humans represent aberrant or accidental hosts. Recently, there has been an increasing number of reported clinical cases of dirofilariasis in both animals and humans. It is known that changes in climatic conditions, including increased temperature, relative humidity and rainfall, can contribute to favorable conditions for the development of mosquitoes and larval stages of filarial parasites within the vector. Despite advances in our knowledge of nematodes of the genus Dirofilaria and the pathological changes that they can induce in different hosts, many clinicians are unfamiliar with dirofilariasis. Thus, in clinical settings, nodules associated with dirofilariasis are often misdiagnosed as neoplastic lesions. Often, physicians surgically excise such nodules from affected patients, sometimes in very sensitive or difficult-to-reach anatomical locations, which may be accompanied by complications or serious consequences for the patients' health, including a stressful experience in the period from the discovery of a nodule to a definitive diagnosis.
Gut Microbiota in Advanced Non-small-cell Lung Cancer Receiving Chemo-immunotherapy: An Ancillary Biomarker Study from the Phase III trial JCOG2007 (NIPPON)
Authors: Taiki Hakozaki, Kentaro Tanaka, Yoshimasa Shiraishi, Yuta Sekino, Noriko Mitome, Yusuke Okuma, Tomoiki Aiba, Takahiro Utsumi, Junko Tanizaki, Koichi Azuma, Satoshi Hara, Ryo Morita, Seiji Niho, Toshihide Yokoyama, Ryo Toyozawa, Hidehito Horinouchi, Isamu Okamoto, Yukio Hosomi, Yuichiro Ohe
Journal: Journal of Thoracic Oncology (2025)
Local salient location-aware anomaly mask synthesis for pulmonary disease anomaly detection and lesion localization in CT images
Authors: Huaying Hao, Yitian Zhao, Shaoyi Leng, Yuanyuan Gu, Yuhui Ma, Feiming Wang, Qi Dai, Jianjun Zheng, Yue Liu, Jingfeng Zhang
Journal: Medical Image Analysis (2025)
Safe Activity participation Following Elective Total hip replacement: the SAFE-T investigation
Authors: Ajay Shah, Cari Whyne, Alex Kiss, Hans Kreder, Dawit Gulta, Stephen Chen, Harman Chaudhry
Journal: British Journal of Sports Medicine (2025)

Total hip replacement (THR) is one of the most common elective orthopaedic surgeries performed, with increasing demand among younger individuals. Few evidence-based guidelines exist on safe activity participation following THR, including whether high-intensity sport participation is safe for individuals. The purpose of this study was to identify if increased intensity of physical activity following THR was associated with increased activity-related pain and increased revision rates. Two groups undergoing THR were recruited: preoperative (cohort 1) and 5-7 years postsurgery (cohort 2); both followed for 5 years. Activity was self-reported through validated questionnaires and grouped into categories from 'A' (low intensity, eg, aquafit) to 'F' (high intensity, eg, tennis). The primary outcome was the presence of hip pain during activity (binary variable, Y/N), measured by the association between hip pain and intensity of activity (categories A-F). Secondary outcomes included activity duration, revision rate or a change in patient-reported outcome measures (PROMs). 1098 individuals were included in this study (cohort 1: n=588, cohort 2: n=510). Regression analysis showed no significant interaction between activity intensity and hip pain across all time points. Approximately 20.6% of all activity (11.0% of participants) occurred in the highest intensity categories (E and F); these subjects showed no decrease in activity duration, worsening PROMs or increased revision rates compared with lower intensity activity groups (all p>0.05). When analysing by individual activities, certain activities (eg, snowboarding, squash, tennis and backpacking) were more correlated with hip pain (r>0.60), while others (eg, snorkelling, swimming, home weights, aquafit, cross-country skiing and sledding) were less likely to have hip pain (r<-0.60). This study showed that higher-intensity activities do not lead to decreased activity duration, worsening patient-reported outcomes or increased revision rates following THR, although certain activities may be associated with increased pain. These findings can inform patient counselling after THR.
International Delphi study of clinical and exercise professionals’ opinion of physical activity prescreening and contraindications for participating in postpartum physical activity
Authors: Margie H Davenport, Shefali Christopher, Rita E Deering, Christina Prevett, Sinead Dufour, Milena Forte, Nicole Beamish, Kristi Adamo, Kari Bo, Emma Brockwell, Émilie Brunet-Pagé, Radha Chari, Marlize De Vivo, Karen Fleming, Amal Hassan, Melanie Hayman, Kirstin N Lane, Michelle F Mottola, Sarah E Neil-Sztramko, Rita A Santos-Rocha, Anna Szumilewicz, Stephanie-May Ruchat
Journal: British Journal of Sports Medicine (2025)

Objective To establish expert consensus on prescreening and contraindications to moderate-to-vigorous intensity physical activity (MVPA) during the first year postpartum. Methods A Delphi survey of clinical and exercise professionals working with postpartum women and people was conducted until consensus was reached (≥75% agreement). Round I consisted of questions about relative and absolute contraindications to MVPA. Rounds II and III included additional questions based on the thematic coding of open-ended responses from the previous rounds. The results were used to develop a postpartum MVPA preparticipation screening tool. Results 120 participants completed round I, 105 completed round II and 95 completed round III. Consensus was reached in 46/49 (94%) statements. Twenty-four relative contraindications to MVPA were identified: (loss of consciousness; neurological symptoms; kidney disease; calf pain or swelling suggestive of deep vein thrombosis; severe abdominal pain; vaginal bleeding not associated with menses; postpartum cardiomyopathy; caesarean section with symptoms that worsen with MVPA; unstable hypertension; eating disorder; malnutrition; anaemia; excessive fatigue; fractures or other significant musculoskeletal injuries; haemodynamic instability; breathing difficulties; acute systemic infection accompanied by fever, body aches, or swollen lymph glands; the new onset of chest pain, discomfort, and other angina-like symptoms with exertion; dizziness or lightheadedness during MVPA; new symptoms of heart disease, stroke; and other medical or physical conditions that may affect the ability to be physically active. Key biopsychosocial barriers to MVPA were identified. Conclusion This Delphi study recommends relative contraindications to MVPA for the first year postpartum that were incorporated into a postpartum MVPA pre-participation screening tool the Get Active Questionnaire for Postpartum.
Unregulated large language models produce medical device-like output
Authors: Gary E. Weissman, Toni Mankowitz, Genevieve P. Kanter
Journal: npj Digital Medicine (2025)

Large language models (LLMs) show considerable promise for clinical decision support (CDS) but none is currently authorized by the Food and Drug Administration (FDA) as a CDS device. We evaluated whether two popular LLMs could be induced to provide device-like CDS output. We found that LLM output readily produced device-like decision support across a range of scenarios, suggesting a need for regulation if LLMs are formally deployed for clinical use.
Identifying and forecasting importation and asymptomatic spreaders of multi-drug resistant organisms in hospital settings
Authors: Jiaming Cui, Jack Heavey, Eili Klein, Gregory R. Madden, Costi D. Sifri, Anil Vullikanti, B. Aditya Prakash
Journal: npj Digital Medicine (2025)

Healthcare-associated infections (HAIs) from multi-drug resistant organisms (MDROs) pose a significant challenge for healthcare systems. Patients can arrive at hospitals already infected ("importation") or acquire infections during their stay ("nosocomial infection"). Many cases, often asymptomatic, complicate rapid identification due to testing limitations and delays. Although recent advancements in mathematical modeling and machine learning have aimed to identify at-risk patients, these methods face challenges: transmission models often overlook valuable electronic health record (EHR) data, while machine learning approaches typically lack mechanistic insights into underlying processes. To address these issues, we propose NeurABM, a novel framework that integrates neural networks and agent-based models (ABM) to leverage the strengths of both methods. NeurABM simultaneously learns a neural network for patient-level importation predictions and an ABM for infection identification. Our findings show that NeurABM significantly outperforms existing methods, marking a breakthrough in accurately identifying importation cases and forecasting future nosocomial infections in clinical practice.
LTA4H improves the tumor microenvironment and prevents HCC progression via targeting the HNRNPA1/LTBP1/TGF-β axis
Authors: Shuai Yang, Xinyao Qiu, Yingcheng Yang, Jing Wu, Shan Wang, Bo Zheng, Jianmin Wu, Tao Zhou, Yangqianwen Zhang, Mixue Bai, Shuowu Liu, Zihan Zhao, Yani Zhang, Yixian Wang, Jinxia Bao, Mengye Wu, Dongdong Xue, Meiyu Bao, Ji Hu, Siyun Shen, Hongyang Wang, Lei Chen
Journal: Cell Reports Medicine (2025)

Highlights•Downregulated LTA4H promotes HCC occurrence and progression•LTA4H ablation fosters CD206+ macrophage via LTBP1-mediated TGF-β activation•LTA4H prevents LTBP1 mRNA maturation and processing in an HNRNPA1-dependent manner•TGF-β blockage sensitizes LTA4H-deficient HCC to immunotherapySummaryLeukotriene A4 hydrolase (LTA4H), an inflammatory mediator, has garnered attention for its role in the development of chronic lung diseases and various cancers. Our study highlights the protective role of LTA4H in hepatocellular carcinoma (HCC) occurrence and progression. LTA4H is downregulated in clinical and mouse HCC tumors. LTA4H deficiency exacerbates hepatocyte damage by restraining JNK activation and promotes CD206+ macrophage polarization through the upregulation of LTBP1 expression and downstream transforming growth factor β (TGF-β) secretion and activation. Mechanistically, LTA4H induces heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) phosphorylation, enhancing their interaction and leading to the functional inhibition of HNRNPA1 in regulating Ltbp1 mRNA maturation and processing in the nucleus. LTA4H-deficient patients exhibit poor prognosis and immunotherapy resistance. Combination therapy targeting TGF-β and PD-1 significantly improves the immunotherapy resistance of LTA4H-knockout Hepa1-6 tumors. Our findings reveal the previously unreported role of LTA4H in regulating the tumor microenvironment and provide insights into potential diagnostic and therapeutic strategies for patients with LTA4H-deficient HCC.Graphical abstract
Interferon-γ-stimulated antigen-presenting cancer-associated fibroblasts hinder neoadjuvant chemoimmunotherapy efficacy in lung cancer
Authors: Zhengqi Cao, Zhouwenli Meng, Jian Li, Yu Tian, Li Lu, Anni Wang, Jia Huang, Jingze Wang, Jing Sun, Lixuan Chen, Shun Lu, Ziming Li
Journal: Cell Reports Medicine (2025)

Highlights•apCAFs are associated with unfavorable outcomes in NSCLC patients receiving NCIT•apCAFs' expansion is triggered by IFN-γ via the JAK1/2-STAT1 pathway•apCAFs promote the formation of FOXP1+Tregs through the PD-L2-RGMB axis•Targeting apCAFs by the blockade of the PD-L2-RGMB axis improves immunotherapy efficacySummaryConventional neoadjuvant chemotherapy provides limited benefit for patients with resectable non-small cell lung cancer (NSCLC). Recently, neoadjuvant chemoimmunotherapy (NCIT) has transformed the perioperative management of NSCLC by priming systemic anti-tumor immunity before surgery, yet it remains ineffective for at least 50% of patients. Through single-cell sequencing analysis of our NCIT cohort, we identify that antigen-presenting cancer-associated fibroblasts (apCAFs) can impede the efficacy of NCIT. Using a custom cancer-associated fibroblast biobank, we uncover that interferon (IFN)-γ stimulates apCAF expansion via the JAK1/2-STAT1-IFI6/27 pathway. Mechanistically, apCAFs significantly contribute to PD-L2 expression in the tumor microenvironment (TME), triggering the accumulation of FOXP1+regulatory T cells (Tregs) through the PD-L2-RGMB axis. Reprogramming apCAFs by inhibiting the IFN-γ pathway or blocking the PD-L2-RGMB axis substantially mitigates apCAFs-mediated FOXP1+Tregs' expansion. In summary, we reveal the role of apCAFs in compromising NCIT efficacy and propose applications for anti-PD-L2/RGMB regimens to synergize with anti-PD1 therapies by targeting apCAFs.Graphical abstract
Engineered human myogenic cells in hydrogels generate innervated vascularized myofibers within dystrophic mouse muscle on long-term engraftment
Authors: Anna Kowala, James Boot, Jinhong Meng, Charles A. Mein, Olivier Pourquié, John T. Connelly, Jennifer E. Morgan, Yung-Yao Lin
Journal: Cell Reports Medicine (2025)

Highlights•A clinically relevant transplantation strategy without modulation of host muscles•Engineered human myogenic cells in hydrogels are engraftable and safe•Long-term engraftment with innervation and vascularization in dystrophic mice•Human PAX7+ cells populate the satellite cell nicheSummaryTransplantation of human myogenic progenitor cells (MPCs) is a promising therapeutic strategy for treating muscle-wasting diseases, e.g., Duchenne muscular dystrophy (DMD). To increase engraftment efficiency of donor stem cells, modulation of host muscles is required, significantly limiting their clinical translation. Here, we develop a clinically relevant transplantation strategy synergizing hydrogel-mediated delivery and engineered human MPCs generated from CRISPR-corrected DMD patient-derived pluripotent stem cells. We demonstrate that donor-derived human myofibers produce full-length dystrophin at 4 weeks and 5–6 months (long-term) after transplantation in the unmodulated muscles of the dystrophin-deficient mouse model of DMD. Remarkably, human myofibers are innervated by mouse motor neurons forming neuromuscular junctions and supported by vascularization after long-term engraftment in dystrophic mice. PAX7+ cells of human origin populate the satellite cell niche. There was no evidence of tumorigenesis in mice engrafted with hydrogel-encapsulated human MPCs. Our results provide a proof of concept in developing hydrogel-based cell therapy for muscle-wasting diseases.Graphical abstract
Primary ciliary protein kinase A activity in the prefrontal cortex modulates stress in mice
Authors: Jiajun Yang, Yingjie Dong, Jie Liu, Yuwei Peng, Ding Wang, Lei Li, Xiaoqing Hu, Jinfeng Li, Liang Wang, Jun Chu, Jian Ma, Hang Shi, Song-Hai Shi
Journal: Neuron (2025)
Neoadjuvant fuzuloparib combined with abiraterone for localized high-risk prostate cancer (FAST-PC): A single-arm phase 2 study
Authors: Tingwei Zhang, Beihe Wang, Yu Wei, Hualei Gan, Bangwei Fang, Xiaomeng Li, Junlong Wu, Xiaojie Bian, Jianfei Wang, Stephen J. Freedland, Shenglin Huang, Dingwei Ye, Yao Zhu
Journal: Cell Reports Medicine (2025)

Highlights•Neoadjuvant PARPi + ARSi shows efficacy with manageable toxicity in high-risk PCa•Biallelic HRR/BRCA2 alterations correlate with faster PSA decline•Post-treatment analysis reveals MYC suppression and reduced proliferation-related pathways•Drug-tolerant persister cells exhibit enhanced EMT and AP-1 activationSummaryPreclinical studies suggest synergistic effects between androgen receptor inhibitors and poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors. This phase 2 trial (NCT05223582) evaluates neoadjuvant fuzuloparib plus abiraterone in 35 treatment-naive men with localized high-risk prostate cancer. Patients receive six cycles of therapy followed by radical prostatectomy. Primary endpoints are pathological complete response (pCR) and minimal residual disease (MRD, ≤5 mm). The combined pCR/MRD rate is 46% (95% confidence interval [CI]: 29%–63%), with a 53% 2-year biochemical progression-free survival rate. Grade ≥3 adverse events occur in 23% of patients. Biallelic homologous recombination repair/BRCA2 alterations correlate with faster prostate-specific antigen decline. Post-treatment genomic analyses reveal reduced MYC amplification and proliferation markers, alongside activated epithelial-mesenchymal transition/activator protein 1 (AP-1) pathways. The trial meets its primary endpoint, demonstrating feasibility and preliminary efficacy, while exploratory biomarkers may guide future studies.Graphical abstract
Single extracellular vesicle detection assay identifies membrane-associated α-synuclein as an early-stage biomarker in Parkinson’s disease
Authors: Shijun Yan, Wenjing Zhang, Xinying Li, Suman Dutta, Andrew R. Castle, Yiming Liu, Anis Sahoo, Chor Lai Lam, Nicholas J.F. Gatford, Michele T. Hu, Chen-zhong Li, Cheng Jiang, Bowen Shu, George K. Tofaris
Journal: Cell Reports Medicine (2025)

Highlights•Droplet-based assay for precise multiplexed quantification of EV membrane proteins•α-Synuclein is associated with the membrane on the surface of L1CAM+ neuronal EVs•α-Synuclein L1CAM+ EV membrane association increases under pathological conditions•EV membrane α-synuclein is an improved biomarker for early Parkinson's diagnosticsSummaryAccurate diagnosis of early Parkinson's disease requires platforms suitable for detecting minute amounts of neuronally derived biomarkers in the massive protein excess of easily accessible biofluids such as blood. Here, we describe an on-chip droplet-confined fluorescence reporting assay that identified α-synuclein on the membrane of L1CAM+ extracellular vesicles (EVs) immunocaptured from human serum and corroborate this finding by super-resolution direct stochastic optical reconstruction microscopy (dSTORM) microscopy. Using conditioned media from neuroblastoma cells expressing α-synuclein mutants or patient-derived induced pluripotent stem cell (iPSC) neurons with α-synuclein gene triplication, we found that association of α-synuclein with the L1CAM+ EV surface is increased under pathological conditions. Accordingly, this readout, as measured by the droplet-based assay, is an improved predictive biomarker in the prodromal phase (area under the receiver operating characteristic curve [AUC] = 0.93) or diagnostic biomarker in the clinical phase (AUC = 0.95) of Parkinson's disease. More broadly, our platform will simplify the assessment of EV membrane proteins and facilitate their application as diagnostic biomarkers across diverse clinical indications.Graphical abstract
TRPM2 overactivation drives hyperlipidemia-induced dysfunction of myeloid cells and neurovascular units
Authors: Pengyu Zong, Cindy Li, Jianlin Feng, Zhichao Yue, Nicholas Legere, Albert S. Yu, Fahad Shah, Adrianna Perez, Zhu Li, Evan Jellison, Yasuo Mori, Barbara Miller, Rajkumar Verma, Bruce Liang, Lixia Yue
Journal: Cell Reports Medicine (2025)

Highlights•TRPM2 in peripheral leukocytes correlates with plasma lipid levels in humans•TRPM2 drives the abnormal activation of peripheral leukocytes induced by lipids•Hyperlipidemia upregulates TRPM2 expression, enhancing ischemic vulnerability•TRPM2 inhibition mitigates ischemic stroke aggravated by hyperlipidemiaSummaryHyperlipidemia induces cellular dysfunction and is strongly linked to various diseases. The transient receptor potential channel melastatin 2 (TRPM2) plays a critical role in endothelial injury, immune cell activation, and neuronal death. We reveal that TRPM2 expression in human peripheral leukocytes strongly correlates with plasma lipid levels. In middle-aged Apoe−/− mice, global, myeloid, and endothelial TRPM2 knockout or TRPM2 inhibition abolishes the hyperlipidemia-induced exacerbation of ischemic brain injury suggesting that TRPM2 overactivity caused by hyperlipidemia predisposes these cells to dysfunction during ischemia. Using a clinically relevant ischemic brain injury mouse model, we demonstrate TRPM2's pivotal role in mediating hyperlipidemia's detrimental effects on myeloid cells and neurovascular units. Our findings suggest that TRPM2 is a promising therapeutic target for alleviating neurodegenerative diseases exacerbated by hyperlipidemia, such as ischemic stroke. These results also highlight TRPM2 expression in peripheral blood as a potential biomarker for predicting stroke outcomes in hyperlipidemic patients.Graphical abstract