tbuckley/cabot-search huggingface dataset:
Carboplatin, etoposide, atezolizumab, and bevacizumab in the first-line treatment of patients with extensive stage small-cell lung cancer: the GOIRC-01-2019 CeLEBrATE study
Authors: Giuseppe Lamberti, Karim Rihawi, Francesca Mazzoni, Ferdinando Riccardi, Alessandro Follador, Marcello Tiseo, Antonio Frassoldati, Ida Colantonio, Andrea Bonetti, Carlo Genova, Donatella Giardina, Federica Bertolini, Saverio Cinieri, Giulia Pasello, Matteo Brighenti, Elisa Andrini, Michele Tognetto, Luca Boni, Andrea Ardizzoni
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background The addition of a programmed death-ligand 1 (PD-L1) inhibitor, either atezolizumab or durvalumab, to platinum-etoposide prolonged survival in a limited subset of patients with extensive-stage small-cell lung cancer (ES-SCLC). Preclinical studies demonstrated synergistic antitumor activity of combined vascular endothelial growth factor receptor and PD-L1 inhibition in SCLC. Since bevacizumab added to platinum-etoposide was safe and active in ES-SCLC, we investigated the efficacy of atezolizumab, bevacizumab, carboplatin, and etoposide as first-line treatment of ES-SCLC. Methods The CeLEBrATE study is an Italian multicentric single-arm phase II trial of carboplatin (area under the curve 5 ml/min), etoposide (100 mg/sqm), bevacizumab (7.5 mg/kg), and atezolizumab (1,200 mg) every 3 weeks (q3w) for four to six courses, followed by bevacizumab and atezolizumab maintenance q3w in patients with ES-SCLC and no contraindications to immunotherapy or antiangiogenic therapy. Patients with asymptomatic brain metastases were eligible. Prophylactic cranial irradiation and consolidation thoracic external radiotherapy were not permitted while on study treatment. Primary endpoint was overall survival (OS) rate at 1 year. Results 53 patients were enrolled (45.3% women, median age 65 years) and received at least one dose of study treatment. At a median follow-up time of 23.4 months (95% CI: 21.1 to 26.0), the 1-year OS rate was 61.8% (90% CI: 50.7% to 72.8%; p=0.04), with a median OS of 12.9 months (95% CI: 11.6 to 17.5). Median progression-free survival was 6.2 months (95% CI: 5.4 to 6.6) and objective response rate was 83.3% (95% CI: 69.8% to 92.5%). Grade 3–4 adverse events were reported in 34 patients (64.2%) leading to dose reductions in 24 (45.3%), and dose delays in 39 (73.9%) and 32 (69.6%) during the induction and maintenance phase, respectively. 19 (35.8%) treatment-related serious adverse events were reported. Conclusion The CeLEBrATE study met its primary objective demonstrating a signal of efficacy of bevacizumab, atezolizumab, carboplatin, and etoposide in the first-line treatment of patients with ES-SCLC. Trial registration number GOIRC-01–2019 ML41241, Eudract Number: 2019-003798-2.
Distinct gut microbiota and metabolome features of tissue-specific insulin resistance in overweight and obesity
Authors: Kelly M. Jardon, Alexander Umanets, Anouk Gijbels, Inez Trouwborst, Gabby B. Hul, Els Siebelink, Lars M.M. Vliex, Jacco J.A.J. Bastings, Rosa Argamasilla, Elodie Chenal, Koen Venema, Lydia A. Afman, Gijs H. Goossens, Ellen E. Blaak
Journal: Gut Microbes (2025)

Insulin resistance (IR) is an early marker of cardiometabolic deterioration which may develop heterogeneously in key metabolic organs, including the liver (LIR) and skeletal muscle (MIR). This tissue-specific IR is characterized by distinct metabolic signatures, but the role of the gut microbiota in its etiology remains unclear. Here, we profiled the gut microbiota, its metabolites and the plasma metabolome in individuals with either a LIR or MIR phenotype (n = 233). We observed distinct microbial community structures LIR and MIR, and higher short-chain fatty acid (SCFA) producing bacteria, fecal SCFAs and branched-chain fatty acids and a higher postprandial plasma glucagon-like-peptide-1 response in LIR. In addition, we found variations in metabolome profiles and phenotype-specific associations between microbial taxa and functional metabolite groups. Overall, our study highlights association between gut microbiota and its metabolites composition with IR heterogeneity that can be targeted in precision-based strategies to improve cardiometabolic health. Clinicaltrials.gov registration: NCT03708419.
Peripheral T‐ and natural killer‐cell lymphomas: ESMO‐EHA Clinical Practice Guideline for diagnosis, treatment, and follow‐up
Authors: Francesco d'Amore, Massimo Federico, Laurence de Leval, Fredrik Ellin, Olivier Hermine, Won Seog Kim, François Lemonnier, Joost S. P. Vermaat, Gerald Wulf, Christian Buske, Martin Dreyling, Mats Jerkeman
Journal: HemaSphere (2025)
Clinical assessment and interpretation of dysarthria in ALS using attention based deep learning AI models
Authors: Michele Merler, Carla Agurto, Julian Peller, Esteban Roitberg, Alan Taitz, Marcos A Trevisan, Indu Navar, James D Berry, Ernest Fraenkel, Lyle W Ostrow, Guillermo A Cecchi, Raquel Norel
Journal: npj Digital Medicine (2025)

Speech dysarthria is a key symptom of neurological conditions like ALS, yet existing AI models designed to analyze it from audio signal rely on handcrafted features with limited inference performance. Deep learning approaches improve accuracy but lack interpretability. We propose an attention-based deep learning AI model to assess dysarthria severity based on listener effort ratings. Using 2,102 recordings from 125 participants, rated by three speech-language pathologists on a 100-point scale, we trained models directly from recordings collected remotely. Our best model achieved R2 of 0.92 and RMSE of 6.78. Attention-based interpretability identified key phonemes, such as vowel sounds influenced by 'r' (e.g., "car," "more"), and isolated inspiration sounds as markers of speech deterioration. This model enhances precision in dysarthria assessment while maintaining clinical interpretability. By improving sensitivity to subtle speech changes, it offers a valuable tool for research and patient care in ALS and other neurological disorders.
Atrial remodelling and atrial fibrillation self-sustaining: the role of circulating circDGCR8
Authors: Yuanfeng Gao, Ying Dong, Nan Jiang, Hanrui Zhang, Zheng Liu, Qianhui Wang, Yuan Fu, Jing Li, Zhiqing Li, Huize Pan, Xianing Zheng, Lingyu Zhan, Xinchun Yang, Li Xu, Mulei Chen
Journal: Cardiovascular Research (2025)

Abstract Aims The prediction of atrial fibrillation (AF) progression and post-ablation recurrence is currently based on empirical estimates, leading to suboptimal predictive accuracy. This study investigates whether atrial remodelling, a key factor in the severity of atrial cardiomyopathy, could serve as a shared substrate influencing both AF progression and recurrence. We aimed to identify circular RNAs (circRNAs) associated with atrial remodelling and to evaluate their ability to predict AF progression and recurrence. Methods and results We assessed the differential expression of plasma circRNAs between paroxysmal (PAF) and persistent AF (PsAF) patients using microarray analysis. Selected candidate circRNAs were validated through qPCR following rigorous statistical and bioinformatics analysis. circDGCR8 was consistently found to be up-regulated in PsAF compared with PAF patients. Additionally, circDGCR8 was significantly up-regulated in human atrial fibroblasts treated with angiotensin II (AngII). Gain- and loss-of-function studies suggested that circDGCR8 could promote atrial remodelling at cellular level by enhancing collagen production and fibroblast proliferation. Overexpression of circDGCR8 in human cardiac fibroblasts significantly altered the gene expression spectrum, impacting pathways including IL-17 signalling and TNF signalling. Moreover, circDGCR8 levels were positively correlated with atrial fibrosis, as indicated by increased percentages of low voltage zones. The predictive value of circDGCR8 was evaluated in two cohorts: (i) PAF patients monitored for 36 months with progression to PsAF as the endpoint, and (ii) AF patients who underwent radiofrequency ablation followed for 12 months to assess recurrence. In both cohorts, higher level of circDGCR8 was associated with increased risks of AF progression and post-ablation recurrence. Conclusion Our results suggest that circDGCR8, associated with atrial remodelling, holds potential as a predictive biomarker for both AF progression and post-ablation recurrence.
Enhancing Attention Network Spatiotemporal Dynamics for Motor Rehabilitation in Parkinson's Disease
Authors: Guangying Pei, Mengxuan Hu, Jian Ouyang, Zhaohui Jin, Kexin Wang, Detao Meng, Yixuan Wang, Keke Chen, Li Wang, Li-Zhi Cao, Shintaro Funahashi, Tianyi Yan, Boyan Fang
Journal: Cyborg and Bionic Systems (2025)
Early-life and concurrent predictors of the healthy adolescent microbiome in a cohort study
Authors: Hannah E Laue, Amy D Willis, Fang Wang, Melinda C MacDougall, Yingying Xu, Margaret R Karagas, Juliette C Madan, Abby F Fleisch, Bruce P Lanphear, Kim M Cecil, Kimberly Yolton, Aimin Chen, Jessie P Buckley, Joseph M Braun
Journal: Genome Medicine (2025)

The microbiome of adolescents is poorly understood, as are factors influencing its composition. We aimed to describe the healthy adolescent microbiome and identify early-life and concurrent predictors of its composition. We performed metagenomic sequencing of 247 fecal specimens from 167 adolescents aged 11-14 years participating in the Health Outcomes and Measures of the Environment (HOME) Study, a longitudinal pregnancy and birth cohort (Cincinnati, OH). We described common features of the adolescent gut microbiome and applied self-organizing maps (SOMs)-a machine-learning approach-to identify distinct microbial profiles (n = 4). Using prospectively collected data on sociodemographic characteristics, lifestyle, diet, and sexual maturation, we identified early-life and concurrent factors associated with microbial diversity and phylum relative abundance with linear regression models and composition with Kruskal-Wallis and Fisher's exact tests. We found that household income and other sociodemographic factors were consistent predictors of the microbiome, with higher income associated with lower diversity and differential relative abundances of Firmicutes (increased) and Actinobacteria (decreased). Sexual maturation, distinct from chronological age, was related to higher diversity in females and differences in phylum relative abundances and compositional profiles in both males and females. Our study suggests that adolescence is a unique window for gut microbial composition and that it may be shaped by both early-life and concurrent exposures, highlighting its potential in future epidemiologic research.
Development of DNase‐1 Loaded Polymeric Nanoparticles Synthesized by Inverse Flash Nanoprecipitation for Neutrophil‐Mediated Drug Delivery to In Vitro Thrombi
Authors: Sophie Maiocchi, Erica E. Burnham, Ana Cartaya, Veronica Lisi, Nancy Buechler, Rachel Pollard, Danial Babaki, Wolfgang Bergmeier, Nathalie M. Pinkerton, Edward M. Bahnson
Journal: Advanced Healthcare Materials (2025)

Abstract Activated neutrophils release Neutrophil Extracellular Traps (NETs), comprising decondensed chromatin, peroxidases, and serine proteases, which aid in host defense but are also implicated in thrombosis and resistance to thrombolysis. Recombinant DNase 1, which degrades NETs, may aid in thrombus dissolution synergistically with fibrinolytics. However, its short half‐life and susceptibility to plasma proteases limit its therapeutic applicability. To address these limitations, DNase1 is encapsulated into polymeric nanoparticles (DNPs) using inverse Flash Nanoprecipitation (iFNP), a scalable nanoparticle synthesis technique. Previously only used with model proteins, the study demonstrates for the first time the feasibility of extending iFNP to the encapsulation of therapeutic proteins. Conditions that promote DNase1 solubility, preserve activity, and demonstrate release resulting in ex vivo NET degradation are detailed. Furthermore, the use of neutrophils, the source of NETs, as carriers for DNPs to enhance targeted delivery is investigated. These findings confirm that DNP‐loaded neutrophils maintain key functionalities, including viability and oxidative burst, and associate with in vitro blood clots to deliver nanoparticles, and DNase1 protein. This study not only extends the feasibility of applying iFNP to encapsulate therapeutic proteins into polymeric nanoparticles, a promising alternative to lipid nanoparticles, but also contributes to the emerging literature on neutrophils as delivery vectors for nanocarriers.
Regulation of H3K4me3 breadth and MYC expression by the SETD1B catalytic domain in MLL-rearranged leukemia
Authors: Shintaro Izumi, Ko Ohtani, Makoto Matsumoto, Seito Shibata, Bahityar Rahmutulla, Masaki Fukuyo, Mitsutaka Nishimoto, Hideo Miyagawa, Emiko Sakaida, Koutaro Yokote, Issay Kitabayashi, Kimi Araki, Atsushi Kaneda, Takayuki Hoshii
Journal: Leukemia (2025)

Abstract Histone H3 lysine 4 trimethylation (H3K4me3) is abundant in mixed-lineage leukemia-rearranged (MLL-r) acute myeloid leukemia (AML) cells; however, the responsible enzymes and their roles remain unclear. This study aimed to identify the modifier responsible for high H3K4me3 modification in MLL-r leukemia and its downstream targets essential for the cell proliferation. Here, we performed a CRISPR-tiling screen against known H3K4 methylation modifiers in an MLL-r AML model. Disrupting the SETD1B catalytic SET domain caused depletion of FLT3-ITD or Nras G12D -expressing AML cells, and gene expression downregulation, particularly in the MYC pathway. SETD1B SET domain loss results in a significant decrease in H3K4me3 breadth. Exogenous MYC expression or disrupting H3K4 demethylase KDM5C significantly restored growth defects in SETD1B SET domain-mutant cells. These data indicated that SETD1B was required for H3K4me3 breadth and MYC expression. Thus, a thorough understanding of SETD1B-mediated H3K4me3 breadth is critical for developing markers and therapies for MYC-dependent leukemia subtypes.
Peak analysis of cell-free RNA finds recurrently protected narrow regions with clinical potential
Authors: Pengfei Bao, Taiwei Wang, Xiaofan Liu, Shaozhen Xing, Hanjin Ruan, Hongli Ma, Yuhuan Tao, Qing Zhan, Efres Belmonte-Reche, Lizheng Qin, Zhengxue Han, Minghui Mao, Mengtao Li, Zhi John Lu
Journal: Genome biology (2025)

Cell-free RNAs (cfRNAs) can be detected in biofluids and have emerged as valuable disease biomarkers. Accurate identification of the fragmented cfRNA signals, especially those originating from pathological cells, is crucial for understanding their biological functions and clinical value. However, many challenges still need to be addressed for their application, including developing specific analysis methods and translating cfRNA fragments with biological support into clinical applications. We present cfPeak, a novel method combining statistics and machine learning models to detect the fragmented cfRNA signals effectively. When test in real and artificial cfRNA sequencing (cfRNA-seq) data, cfPeak shows an improved performance compared with other applicable methods. We reveal that narrow cfRNA peaks preferentially overlap with protein binding sites, vesicle-sorting sites, structural sites, and novel small non-coding RNAs (sncRNAs). When applied in clinical cohorts, cfPeak identified cfRNA peaks in patients' plasma that enable cancer detection and are informative of cancer types and metastasis. Our study fills the gap in the current small cfRNA-seq analysis at fragment-scale and builds a bridge to the scientific discovery in cfRNA fragmentomics. We demonstrate the significance of finding low abundant tissue-derived signals in small cfRNA and prove the feasibility for application in liquid biopsy.
Development of a whole-exome sequencing kit to facilitate porcine biomedical research
Authors: Vishwaarth Vijayakumar, Tanvi Joshi, Lobna Elkhadragy, Lawrence B Schook, Ron C Gaba, Mohammed El-Kebir, Kyle M Schachtschneider
Journal: Genome biology (2025)

Abstract Background It is important for porcine models to replicate gene mutations present in human diseases to improve the translatability of animal studies. In this study, the high efficacy of a whole exome sequencing kit was demonstrated for the improved pig reference genome ( Sus scrofa 11.1) to profile biomedically relevant swine breeds and enable high-depth sequencing required for intratumor heterogeneity profiling. Results We identify a total of 751,624 single nucleotide variants (SNVs) and 113,597 insertions and deletions (INDELs) across 93 samples from 12 porcine breeds. The identified mutations and affected pathways are correlated to muscle-to-fat ratios between different porcine breeds and further inform their utility as models of obesity and cardiovascular disease. Finally, 7935 SNVs and 358 INDELs are present in an Oncopig hepatocellular carcinoma (HCC) cell line and samples from a single Oncopig HCC tumor, with pathways related to hepatic fibrosis, WNT/B-catenin, ATM signaling, and p53 signaling enriched. Conclusions These results demonstrate the kit’s high efficacy and utility for identifying mutations in the context of obesity, cardiovascular disease, and cancer across a range of pig models used in biomedical research.
ONTraC characterizes spatially continuous variations of tissue microenvironment through niche trajectory analysis
Authors: Wen Wang, Shiwei Zheng, Sujung Crystal Shin, Joselyn Cristina Chávez-Fuentes, Guo-Cheng Yuan
Journal: Genome biology (2025)

Abstract Recent technological advances enable mapping of tissue spatial organization at single-cell resolution, but methods for analyzing spatially continuous microenvironments are still lacking. We introduce ONTraC, a graph neural network-based framework for constructing spatial trajectories at niche-level. Through benchmarking analyses using multiple simulated and real datasets, we show that ONTraC outperforms existing methods. ONTraC captures both normal anatomical structures and disease-associated tissue microenvironment changes. In addition, it identifies tissue microenvironment-dependent shifts in gene expression, regulatory network, and cell–cell interaction patterns. Taken together, ONTraC provides a useful framework for characterizing the structural and functional organization of tissue microenvironments.
Few‐Shot Identification of Active Therapeutic Peptide Networking with Gradient Dynamics against Cancer
Authors: Runzhi Xia, Wei Sun, Jiaming Liang, Shidong Wang, Fuqiang Gao, Yawei Liu, Liu Wang, Hongjie Zhang, Chao Ma, Kai Liu
Journal: Advanced Healthcare Materials (2025)

The treatment of osteosarcoma remains challenging due to limitations of chemotherapy. Anticancer peptides present a promising avenue as alternative therapeutic agents; however, they encounter significant drawbacks, including susceptibility to proteolytic degradation and constrained selectivity toward tumor. Herein, a few-shot peptide screening strategy is developed, yielding identification of RT2 (tumor-lytic peptide) and E16 (ionic-responsive self-assembling peptide). Their fusion E16-RT2 (ER) is engineered, exhibiting 175% enhanced tumor-selective cytotoxicity and cancer membrane targeting. By leveraging the dual functionality of ER, an injectable hydrogel encapsulating doxorubicin is developed, enabling gradient dynamics for tumor-specific drug release and sustained therapeutic efficacy (>9 d). Moreover, there is no systemic/organ toxicity in murine models dosed with the therapeutic network. The potential mechanism is proposed: charge-guided ER localization disrupts cancer membrane integrity, enabling therapeutics influx while sparing healthy cells, coupled with network degradation kinetics ensuring prolonged drug retention. This rational design paradigm establishes a clinically translatable platform combining tumor-perturbing peptides with smart biomaterials, effectively overcoming limitations of conventional agents. The demonstrated "safety-efficacy" profile positions this approach as a viable strategy for cancer treatment.
Tissue‐Microenvironment‐Responsive Self‐Assembling Peptide Nanoshells Boost Pirfenidone Efficacy in the Treatment of Liver Fibrosis
Authors: Ruifang Li, Yifan Tai, Xinyan Zhang, Zhen Liu, Haipeng Si, Deling Kong, Lili Zhao, Jia Li, Adam C. Midgley
Journal: Advanced Healthcare Materials (2025)

Chronic liver disease culminates in liver fibrosis, responsible for substantial worldwide morbidity and mortality. Traditional chemical drugs that have proven effective at treating other types of tissue fibrosis may be repurposed for treating liver fibrosis but face inefficient outcomes or elicit undesirable side effects. Hepatic-targeted drug nanocarriers offer a potential strategy for achieving localized drug release to effectively alleviate liver fibrosis while mitigating off-target effects. Elevated levels of fibroblast activation protein-α (FAP-α) have been associated with liver fibrosis and the presence of platelet-derived growth-factor-receptor-β-overexpressing activated hepatic stellate cells. Therefore, FAP-α-responsive nanoshells are developed from hepatic fibrosis targeting peptides to protect and transport pirfenidone (PFD) to fibrotic livers for potentiated therapeutic efficacy. In vitro experiments validate that PFD-loaded hepatic- and fibrosis-targeting nanoshells (PFD@ns) lessen transforming-growth-factor-β1-driven collagen production and activation of hepatic stellate cells. In animal models of liver fibrosis, PFD@ns increase the efficacy of PFD in preventing fibrosis, alleviating proinflammatory cell infiltration, and modulating the PI3K/AKT/mTOR signaling pathway. In conclusion, these findings suggest that the hepatic- and fibrosis-targeted PFD@ns can potentially serve as an effective tool in the treatment of liver fibrosis.
Micro/Nanofibrous Polycaprolactone Scaffolds Loaded with Gentamicin for Improved Antimicrobial Activities under Seawater Immersion
Authors: Kaili Liu, Yanwen Su, Boyuan Wei, Xiaoyu Guo, Yabo Zhang, Songlin Wang, Sirui Zhang, Yuming Kang, Xiaojing Yu, Hui Zhu, Jiankang He
Journal: Advanced Healthcare Materials (2025)

Marine open traumatic brain injuries (oTBI) face high infection risks due to seawater-borne pathogens, demanding dura scaffolds with dual antibacterial and osteogenic functions under seawater immersion. Conventional scaffolds lack this dual capacity. Here, a biomimetic triple-layer polycaprolactone (PCL)-based scaffold is developed. The cerebral-side electrospun layer incorporates gentamicin sulfate (GS) for antibacterial action, while the cranial-side electrohydrodynamically printed rhombic PCL layer contains nano-hydroxyapatite (nHA) to enhance osteogenesis. A middle GS/PCL electrospun layer reinforces mechanical strength. The PCL/GS/nHA scaffold demonstrates suitable mechanical properties, sustained GS release, and low hemolysis. After seawater immersion or direct S. aureus exposure, it maintains potent antibacterial efficacy and biocompatibility. Additionally, nHA promotes osteogenic differentiation of human bone marrow mesenchymal stem cells in vitro. This multi-functional scaffold combines seawater-resistant antimicrobial performance with osteogenic capacity, offering a promising solution for dura repair in marine environments.