tbuckley/cabot-search huggingface dataset:
Erratum: Lipocalin-2 activates hepatic stellate cells and promotes nonalcoholic steatohepatitis in high-fat diet-fed Ob/Ob mice
Authors: Kyung Eun Kim, Jaewoong Lee, Hyun Joo Shin, Eun Ae Jeong, Hye Min Jang, Yu Jeong Ahn, Hyeong Seok An, Jong Youl Lee, Meong Cheol Shin, Soo Kyoung Kim, Won Gi Yoo, Won Ho Kim, Gu Seob Roh
Journal: Hepatology (2025)
Abnormal collagen deposition mediated by cartilage oligomeric matrix protein in the pathogenesis of oral submucous fibrosis
Authors: Yafei Xiong, Xuechun Li, Bincan Sun, Jie Zhang, Xiaoshan Wu, Feng Guo
Journal: International Journal of Oral Science (2025)

Abstract Abnormal accumulation of collagen fibrils is a hallmark feature of oral submucous fibrosis (OSF). However, the precise characteristics and underlying mechanisms remain unclear, impeding the advancement of potential therapeutic approaches. Here, we observed that collagen I, the main component of the extracellular matrix, first accumulated in the lamina propria and subsequently in the submucosa of OSF specimens as the disease progressed. Using RNA-seq and Immunofluorescence in OSF specimens, we screened the cartilage oligomeric matrix protein (COMP) responsible for the abnormal collagen accumulation. Genetic COMP deficiency reduced arecoline-stimulated collagen I deposition significantly in vivo. In comparison, both COMP and collagen I were upregulated under arecoline stimulation in wild-type mice. Human oral buccal mucosal fibroblasts (hBMFs) also exhibited increased secretion of COMP and collagen I after stimulation in vitro. COMP knockdown in hBMFs downregulates arecoline-stimulated collagen I secretion. We further demonstrated that hBMFs present heterogeneous responses to arecoline stimulation, of which COMP-positive fibroblasts secrete more collagen I. Since COMP is a molecular bridge with Fibril-associated collagens with Interrupted Triple helices (FACIT) in the collagen network, we further screened and identified collagen XIV, a FACIT member, co-localizing with both COMP and collagen I. Collagen XIV expression increased under arecoline stimulation in wild-type mice, whereas it was hardly expressed in the Comp -/- mice, even with under stimulation. In summary, we found that COMP may mediates abnormal collagen I deposition by functions with collagen XIV during the progression of OSF, suggesting its potential to be targeted in treating OSF.
Pirfenidone in post-COVID19 pulmonary fibrosis (FIBRO-COVID): a phase 2 randomized clinical trial
Authors: Guadalupe Bermudo, Belén Del Rio, Vanesa Vicens-Zygmunt, Jaume Bordas-Martinez, Marta Hernández, Claudia Valenzuela, Rosalía Laporta, Juan Rigual Bobillo, Karina Portillo, Paloma Millán-Billi, Eva Balcells, Diana Badenes-Bonet, Santi Bolivar, José-Antonio Rodríguez-Portal, Cecilia López Ramirez, Laura Tomás, Koral Fernández de Roitegi, Jacobo Sellarés, Diego Castillo, Jessica González, Silvia Barril, Yasmina Gutiérrez-Rodríguez, Paloma Caballero, Javier Alarcon, Judith Peñafiel, Jose Sanz-Santos, Rosana Blavia, Cristina Caupena, Pilar Segovia, Salud Santos-Pérez, Anna Ferrer, Maria B Badia, Pilar Hereu, Mireya Fuentes, Ana Montes-Worboys, Tomás Franquet, Patricio Luburich, María Molina-Molina
Journal: European Respiratory Journal (2025)

Patients with severe COVID-19 may develop lung fibrosis. Pirfenidone is an anti-fibrotic drug approved for idiopathic pulmonary fibrosis. The efficacy and safety of pirfenidone in patients with fibrotic interstitial lung changes after recovery from severe COVID-19 pneumonia was evaluated. Phase 2, double-blind, placebo-controlled, Spanish multicenter clinical trial randomized to receive pirfenidone or placebo (2:1) for 24-weeks. The primary endpoint was the proportion of patients that improved, considered when percent change in forced vital capacity (FVC) was ≥10% and/or any reduction in the fibrotic score chest high-resolution computed tomography (HRCT). Secondary endpoints included health-related quality of life (HRQoL), exercise capacity, and drug safety profile. From 119 eligible patients, 113 were randomized and 103 were analyzed (pirfenidone n=69, placebo n=34). Most patients were male (73.5%) and were receiving low-dose prednisone; mean age was 63.7 years and body-mass index was 29 kg·m-2. The percentage of patients that improved was similar in the pirfenidone and placebo groups (79.7% versus 82.3%, respectively). The mean predicted FVC (%) increased 12.74 (20.6) with pirfenidone and 4.35 (22.3) with placebo (p=0.071), and the HRCT (%) fibrotic score reduced 5.44 (3.69) with pirfenidone and 2.57 (2.59) with placebo (p=0.52). Clinically meaningful improvement in HRQoL was not statistically different (55.2% in pirfenidone and 39.4% in placebo group, respectively). Exercise capacity, adverse events and hospitalizations were similar between groups. No deaths were reported. The overall improvement in lung function and the HRCT fibrotic score after 6 months with pirfenidone was not significantly different than placebo.
Machine Learning Identification of Patient Phenoclusters in Aortic Regurgitation
Authors: Maan Malahfji, Xin Tan, Yodying Kaolawanich, Mujtaba Saeed, Andrada Guta, Michael J Reardon, William A Zoghbi, Venkateshwar Polsani, Michael Elliott, Raymond Kim, Meng Li, Dipan J Shah
Journal: JACC. Cardiovascular imaging (2025)

Current treatment paradigms assume aortic regurgitation (AR) patients to be a homogenous population, but varied courses of disease progression and outcomes are observed clinically. The aim of this study was to first use unsupervised machine learning to identify unique patient phenoclusters in AR, and subsequently evaluate their prognostic relevance. Clinical and cardiac magnetic resonance (CMR) characterization of moderate or severe AR patients was performed across 4 U.S. Data from 2 centers were used for derivation of phenoclusters and validation was performed in the other 2. The outcome was all-cause death. An unsupervised clustering pipeline, Partition Around Medoids, used 23 clinical and CMR variables to derive patient clusters independent of outcomes. Included were 972 patients with mean age 62 ± 23.2 years, 754 (78%) male, 680 (70%) trileaflet valve, and 330 (34%) underwent valve surgery. Over a median follow-up of 2.58 years (Q1-Q3: 1.03-5.50 years), the overall mortality rate was 12%. Four clusters were derived: 1) a younger predominantly male phenotype with majority of bicuspid aortic valve and high extent of left ventricular (LV) remodeling (1% mortality); 2) older male patients with predominantly tricuspid valves and intermediate outcomes (10% mortality); 3) older predominantly male patients with the highest burden of comorbidities, LV scarring, and dysfunction (22% mortality); and 4) a phenotype of predominantly female patients with high mortality and relatively higher symptoms burden, relatively lower extent of LV remodeling, and rate of aortic valve replacement (20% mortality). The clustering algorithm was independently associated with survival after adjustment for time-dependent aortic valve replacement and traditional risk markers of prognosis in patients with AR (C statistic 0.77 vs 0.75; P = 0.009 in the validation cohort). Unique patient phenoclusters of AR are described using a machine learning approach leveraging comprehensive CMR and clinical characterization. This approach may be an opportunity for a precision medicine approach to enhance risk stratification of patients with AR. Female patients with AR pose a unique phenotype with high mortality, which deserves greater attention.
NIR‐I Light‐Activated Antibiotic Delivery &amp; PDT via TiO<sub>2</sub>/Graphene Metastructure for Enhanced Antibacterial Activity and Osseointegration of Ti Implants
Authors: Minggang Yang, Yufan Zhang, Zhenhao Hou, Jianbo Wu, Fuwei Liu, Jun Wu, Kelvin W.K. Yeung, Wenhao Qian, Xuanyong Liu, Liang Kong, Yunpeng Li, Jiajun Qiu, Guocheng Wang
Journal: Advanced Healthcare Materials (2025)

Abstract Antibiotic therapy is a key strategy for treating infections associated with orthopedic implants, yet its limited effectiveness and potential to disrupt bone healing highlight the need for innovative approaches. Herein, a TiO 2 ‐Graphene (TiO 2 ‐G) metastructure is developed on Ti implant surface using a hydrothermal method coupled with plasma‐enhanced chemical vapor deposition (PECVD), showing strong near‐infrared light (NIR) absorption. The antibiotic doxycycline (DOX) is successfully loaded onto TiO 2 ‐G and exhibited enhanced NIR release. The promising antibacterial efficacy is proven by both in vitro and in vivo tests with NIR irradiation for 5 min, which is ascribed to the synergistic photocatalytic activity of TiO 2 ‐G and NIR‐responsive release of DOX. Interestingly, after 5 min of NIR irradiation, the TiO 2 ‐G metasurface neutralized the immediate negative effects of photodynamics and even upregulated the expression of osteogenic genes (osteocalcin (OPN), osteopontin (BSP), and bone sialoprotein (OCN)), with particularly enhanced effects observed on day 14. Moreover, the sustained release function of TiO 2 ‐G significantly mitigated the cytotoxicity of free antibiotics with antibacterial capabilities comparable to those of TiO 2 ‐G/DOX under NIR irradiation for 5 min. Consequently, the in vivo studies proved that the TiO 2 ‐G metastructure enhanced the osteointegration of the implant even in the absence of infection when loaded with DOX.
Isolation of derivatives from the food-grade probiotic <i>Lactobacillus johnsonii</i> CNCM I-4884 with enhanced anti- <i>Giardia</i> activity
Authors: Anne-Sophie Boucard, Saulius Kulakauskas, Jana Alazzaz, Soraya Chaouch, Mohamed Mammeri, Aaron Millan-Oropeza, Carine Machado, Céline Henry, Christine Péchoux, Holger Richly, Michael Gassel, Philippe Langella, Bruno Polack, Isabelle Florent, Luis G. Bermúdez-Humarán
Journal: Gut Microbes (2025)

Giardiasis, a widespread intestinal parasitosis affecting humans and animals, is a growing concern due to the emergence of drug-resistant strains of G. intestinalis. Probiotics offer a promising alternative for preventing and treating giardiasis. Recent studies have shown that the probiotic Lactobacillus johnsonii CNCM I-4884 inhibits G. intestinalis growth both in vitro and in vivo. This protective effect is largely mediated by bile salt hydrolase (BSH) enzymes, which convert conjugated bile acids (BAs) into free forms that are toxic to the parasite. The objective of this study was to use adaptive evolution to develop stress-resistant derivatives of L. johnsonii CNCM I-4884, with the aim of improving its anti-Giardia activity. Twelve derivatives with enhanced resistance to BAs and reduced autolysis were generated. Among them, derivative M11 exhibited the highest in vitro anti-Giardia effect with enhanced BSH activity. Genomic and proteomic analyses of M11 revealed two SNPs and the upregulation of the global stress response by SigB, which likely contributed to its increased BAs resistance and BSH overproduction. Finally, the anti-Giardia efficacy of M11 was validated in a murine model of giardiasis. In conclusion, our results demonstrate that adaptive evolution is an effective strategy to generate robust food-grade bacteria with improved health benefits.
TP53-centric ctDNA complements PET/CT for non-invasive assessment of pathological complete response and survival after neoadjuvant immunochemotherapy in esophageal squamous cell carcinoma: a prospective cohort study
Authors: Weixiong Yang, Si-Cong Ma, Zengli Fang, Yao Liu, Xin Zhang, Fang Wang, Chenxuan Wang, Yuze Wang, Xiaoyan Wang, Wenfang Chen, Hui Luo, Lingling Yang, Shuishen Zhang, Bo Zeng, Zhenguo Liu, Qiuxiang Ou, Junchao Cai, Sai-Ching Jim Yeung, Chao Cheng
Journal: International Journal of Surgery (2025)
The safety and efficacy of stent-assisted coiling for acutely ruptured cerebral aneurysms: a multicenter prospective registry study (SAVE)
Authors: Gaozhi Li, Shenghao Ding, Jiale Wang, Kuang Zheng, Wenshuai Li, Guohua Mao, Xiaobo Liu, Zheming Zhang, Dianshi Jin, Lang Liu, Qinhua Guo, Qingyuan Liu, Xiaohua Zhang, Edgar Samaniego, Rose Du, Yaohua Pan, Jieqing Wan, Bing Zhao
Journal: International Journal of Surgery (2025)
AutoFRS: an externally validated, annotation-free approach to computational preoperative complication risk stratification in pancreatic surgery – an experimental study
Authors: Fiona R. Kolbinger, Nithya Bhasker, Felix Schön, Daniel Cser, Alex Zwanenburg, Steffen Löck, Sebastian Hempel, André Schulze, Nadiia Skorobohach, Hanna M. Schmeiser, Rosa Klotz, Ralf-Thorsten Hoffmann, Pascal Probst, Beat Müller, Sebastian Bodenstedt, Martin Wagner, Jürgen Weitz, Jens-Peter Kühn, Marius Distler, Stefanie Speidel
Journal: International Journal of Surgery (2025)
Cancer in rural America: Improving access to clinical trials and quality of oncologic care
Authors: Joseph M. Unger, Barbara L. McAneny, Raymond U. Osarogiagbon
Journal: CA A Cancer Journal for Clinicians (2025)

Individuals from rural areas in the United States suffer higher rates of morbidity and mortality from cancer than their urban counterparts. This review is based on the idea that equity-the elimination of unnecessary and preventable differences between groups of individuals-should underlie access to cancer care resources for patients from rural areas. Access to cancer clinical trials serves as the framework for identifying and understanding barriers in access to quality oncologic care. The authors discuss the interplay between rural living, socioeconomic status, culture, and health; and they highlight how economic considerations in rural areas often limit access to clinical trials and oncologic care because economies of scale do not apply in these regions given the requirement for high-quality oncology care even with lower patient volumes. The authors propose solutions to enhance access to clinical trials and improve the quality of oncologic care in rural areas, viewing these aims as ethical and moral imperatives.
Ceria‐Nanoparticle‐Entangled Reticulation for Angiogenic and Therapeutic Embrocation for Multifactorial Approach to Treat Diabetic Wound
Authors: Young Geon Kim, Yunjung Lee, Hyun Jyung Oh, Jinyoung Chu, Gyeong Ho Min, Kang Kim, Jaeseon Lee, Seungmin Baik, Dokyoon Kim, Chi Kyung Kim, Min Soh, Sik Namgoong, Taeghwan Hyeon
Journal: Advanced Healthcare Materials (2025)

The therapeutic efficacy of a nanomedicine or a natural biomaterial can vary in different disorders due to their complex pathophysiology. A nanomedicine that is capable of not only targeting specific pathological cues through functional ligands but also optimizing the therapeutic efficacy of its components throughout the intricate pathways involved in complex disorders is highly desired. Here, ceria-nanoparticle-entangled reticulation for angiogenic and therapeutic embrocation (CERATE), composed of hyaluronic acid, levofloxacin, and the as-synthesized ceria nanoparticles is developed. CERATE is formulated in situ as a rigid nanoparticle-based network that integrates its components intimately using highly diluted concentrations, thereby augmenting the therapeutic efficiency of its individual components. The physical states of CERATE can be altered freely while retaining its integrity, by adjusting the water proportion to accommodate diverse clinical needs. This physically robust CERATE can withstand enzymatical degradation, display antibacterial activity, scavenge reactive oxygen species, and improve the migration and proliferation of fibroblasts by activating the proangiogenic factors. CERATE accelerates the repair of diabetic wounds by promoting both the angiogenesis and the synthesis of collagen. The results demonstrate the effectiveness of a multifactorial approach involving the recruitment of minimally modified biofunctional ligands and nanomaterials altogether with synergistic efficacy in treating complex disorders.
Dominant Role of Distinct Microenvironments on Cartilage Regeneration Fate Using PLGA‐Hydrogel Composite Scaffolds
Authors: Bohui Li, Tian An, Daiying Song, Xujie Lu, Yingying Huo, Yaru Chu, Juncen Li, Yilin Cao, Guangdong Zhou, Yujie Hua, Yu Liu
Journal: Advanced Healthcare Materials (2025)

Currently, bioactive composite scaffolds provide an ideal regenerative microenvironment for cartilage tissue engineering. However, the dominant regulatory role of the microenvironment in cartilage regeneration fate remains elusive, such as in situ auricle, ex situ subcutaneous, and osteogenic regions. Therefore, investigating the influence of distinct microenvironments on cartilage regeneration and long-term outcomes is important. In this study, a universal composite scaffold is developed combining 3D-printed poly(lactic-co-glycolic acid) frameworks with cartilage-specific matrix hydrogels and then systematically explored the crucial role of the microenvironment in determining the fate of cartilage regeneration. These results indicate that the in situ auricular microenvironment effectively promotes the maturation of the regenerative cartilage and maintains its chondrogenic phenotype. In contrast, ex situ subcutaneous microenvironment leads to chondrogenic phenotype loss owing to intense immune-inflammatory responses and vascularization conditions. In the osteogenic microenvironments of cranial sites, although autologous chondrocytes show good cartilage regenerative quality within 12 weeks, they are gradually replaced by regenerative bone, ultimately achieving successful cranial defect repair. Interestingly, these findings provide critical theoretical foundations for revealing the long-term outcomes of engineered cartilage and offer practical guidance for optimizing cartilage regeneration strategies in various microenvironments.
A Drug-Screening Platform for Podocytopathies in Drosophila Nephrocytes
Authors: Dominik Spitz, Jost Wiggering, Chiranth Prakash, Maximilian H. Ulbrich, Ronen Schneider, Tobias Hermle
Journal: Journal of the American Society of Nephrology (2025)

The complex cellular architecture of the glomerular filtration barrier is not recapitulated in vitro, representing a major obstacle for drug screening. This contributes significantly to a therapeutic gap for the heterogeneous diseases affecting the podocyte. Phenotypic drug screening using whole organisms is inherently slow but can reveal entirely unexpected therapies that are unattainable by conventional screening. The Drosophila nephrocyte features a molecularly conserved filtration barrier, suitable for whole-animal screening in podocytopathies. We generated transgenic Drosophila expressing a secretable variant of Green Fluorescent Protein as a genetically encoded tracer for rapid analysis of nephrocyte function. Animals were exposed to drugs in liquid food before recording nephrocyte fluorescence intensity. The slit diaphragm architecture was investigated using immunofluorescence and subsequent automated quantification. The genetically encoded tracer, combined with fast detection through enhanced widefield fluorescence microscopy, provided a faster but reliable screening assay for nephrocyte function compared with the established approach using FITC-albumin ex vivo. Rac1 is a key regulator of the actin cytoskeleton, involved in maintaining podocyte structure and function. In nephrocytes, overexpression of Rac1 resulted in mislocalization of slit diaphragm proteins and deeper membrane invaginations. Since nephrocyte function was further decreased as detected by the novel assay, we used this screening background relevant to podocyte biology for a pilot screen of 100 drugs. We identified significant improvement of nephrocyte function for zacopride, a respective agonist or antagonist of serotonin receptors, which restored the slit diaphragm architecture despite overexpression of Rac1. The mechanism of action of zacopride appeared independent from the orthologs of the mammalian target proteins or direct Rac1 inhibition, suggesting a pleiotropic target. This hit from the pilot screen illustrates the potential of phenotypic drug screening to reveal unexpected therapeutic options. We present a proof-of-concept for whole-animal drug screening using podocyte-like Drosophila nephrocytes.
Artificial intelligence-based multimodal prediction for nuclear grading status and prognosis of clear cell renal cell carcinoma: a multicenter cohort study
Authors: Qingyuan Zheng, Haonan Mei, Xiaodong Weng, Rui Yang, Panpan Jiao, Xinmiao Ni, Xiangxiang Yang, Jiejun Wu, Junjie Fan, Jingping Yuan, Xiuheng Liu, Zhiyuan Chen
Journal: International Journal of Surgery (2025)
Belantamab Mafodotin Plus Proteasome Inhibition Efficacy Versus Comparators in Early Relapsed Myeloma: A Systematic Review and Network Meta‐Analysis
Authors: Joshua Richter, Ajay Nooka, Paula Rodríguez‐Otero, Fredrik Schjesvold, Eirini Katodritou, Emily Combe, Marianne Scott, Leanne Cooper, Indeg Sly, Nick Ballew, Jacopo Bitetti, Natalie Boytsov, Molly Purser, Simon McNamara
Journal: American Journal of Hematology (2025)

In the Phase 3 DREAMM-7 study of patients with relapsed/refractory multiple myeloma (RRMM) who received ≥ 1 prior therapy, belantamab mafodotin plus bortezomib and dexamethasone (BVd) demonstrated a progression-free survival (PFS) benefit versus daratumumab plus bortezomib and dexamethasone (DVd). This study aimed to indirectly compare the efficacy of BVd against alternative regimens in this patient population. A systematic literature review (SLR; December 2021-February 4, 2024) was performed to identify relevant efficacy data. Studies were selected based on the Population-Intervention-Comparators-Outcomes-Study design framework criteria and independently reviewed for inclusion in the network meta-analysis (NMA) if they had a connection to DREAMM-7 (approved in the US or EU, or likely to be a future DREAMM-7 comparator). Each trial had a common comparator arm, allowing for a connected network between the trials and linkage by shared treatments. The primary analysis was PFS in the intent-to-treat population from each study, and secondary analyses examined other endpoints. All endpoints were also evaluated in subgroups by lenalidomide-exposure, -refractoriness, and other patient characteristics. The SLR identified 12 comparator studies comprising 12 comparator regimens (each contained a proteasome inhibitor [bortezomib or carfilzomib] plus dexamethasone), all of which were included in the NMA with the DREAMM-7 study. BVd improved PFS versus all comparators, including daratumumab plus carfilzomib and dexamethasone, isatuximab plus carfilzomib and dexamethasone, and DVd. Overall survival was also improved by belantamab mafodotin plus bortezomib and dexamethasone over the other regimens. This study provides compelling evidence for belantamab mafodotin, plus bortezomib and dexamethasone, in early lines of treatment for RRMM.
Enhancing Form Stability: Shrink‐Resistant Hydrogels Made of Interpenetrating Networks of Recombinant Spider Silk and Collagen‐I
Authors: Xuen J Ng, Tilman U Esser, Vanessa T Trossmann, Christoph Rudisch, Maren Fiedler, Kaveh Roshanbinfar, Zan Lamberger, Philipp Stahlhut, Gregor Lang, Thomas Scheibel, Felix B Engel
Journal: Advanced Healthcare Materials (2025)

Tissue engineering enables the production of tissues and organ-like structures as models for drug testing and mechanistical studies or functional replacements for injured tissues. Available cytocompatible materials are limited in number, suffer from insufficient mechanical properties, and cells interacting with them often cause construct shrinkage. As shape is important for function, identifying cytocompatible, shrink-resistant materials are a major aim. Here, it is shown that hydrogels made of interpenetrating networks of collagen-I and recombinant spider silk protein eADF4(C16)-RGD nanofibrils exhibit synergistic and tunable mechanical properties. Composite hydrogels allow cell adhesion and spreading and are resistant to shrinkage mediated by fibroblasts, C2C12 myoblasts, and human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes. Myoblasts differentiate and fuse into myotubes, and hiPSC-cardiomyocytes can be cultured long-term, show spontaneous contractions, and remain drug responsive. Collectively, a novel composite material is developed to overcome the challenge of post-fabrication matrix shrinkage conferring high shape fidelity suitable for tissue engineering.