tbuckley/cabot-search huggingface dataset:
Machine Learning–Based Models for Advanced Fibrosis and Cirrhosis Diagnosis in Chronic Hepatitis B Patients With Hepatic Steatosis
Authors: Fajuan Rui, Liang Xu, Yee Hui Yeo, Yayun Xu, Wenjing Ni, Youwen Tan, Qi Zheng, Xiaorong Tian, Qing-Lei Zeng, Zebao He, Yuanwang Qiu, Chuanwu Zhu, Weimao Ding, Jian Wang, Rui Huang, Qi Xue, Xueqi Wang, Yunliang Chen, Junqing Fan, Zhiwen Fan, Eiichi Ogawa, Min-Sun Kwak, Xiaolong Qi, Junping Shi, Vincent Wai-Sun Wong, Chao Wu, Jie Li
Journal: Clinical Gastroenterology and Hepatology (2024)
Comprehensive profiling of lipid metabolic reprogramming expands precision medicine for hepatocellular carcinoma
Authors: Qingbin Liu, Xiangyu Zhang, Jingjing Qi, Xinchen Tian, Eva Dovjak, Jiaqi Zhang, Honghuan Du, Ni Zhang, Jing Zhao, Yiming Zhang, Lijuan Wang, Yangang Wei, Chenqiao Liu, Ruikun Qian, Longquan Xiang, Weiyang Li, Peng Xiu, Changlin Ma, Yong Yu, Shulong Jiang
Journal: Hepatology (2024)

Background and Aims: Liver HCC is the second leading cause of cancer-related deaths worldwide. The heterogeneity of this malignancy is driven by a wide range of genetic alterations, leading to a lack of effective therapeutic options. In this study, we conducted a systematic multi-omics characterization of HCC to uncover its metabolic reprogramming signature. Approach and Results: Through a comprehensive analysis incorporating transcriptomic, metabolomic, and lipidomic investigations, we identified significant changes in metabolic pathways related to glucose flux, lipid oxidation and degradation, and de novo lipogenesis in HCC. The lipidomic analysis revealed abnormal alterations in glycerol-lipids, phosphatidylcholine, and sphingolipid derivatives. Machine-learning techniques identified a panel of genes associated with lipid metabolism as common biomarkers for HCC across different etiologies. Our findings suggest that targeting phosphatidylcholine with saturated fatty acids and long-chain sphingolipid biosynthesis pathways, particularly by inhibiting lysophosphatidylcholine acyltransferase 1 ( LPCAT1 ) and ceramide synthase 5 ( CERS5 ) as potential therapeutic strategies for HCC in vivo and in vitro. Notably, our data revealed an oncogenic role of CERS5 in promoting tumor progression through lipophagy. Conclusions: In conclusion, our study elucidates the metabolic reprogramming nature of lipid metabolism in HCC, identifies prognostic markers and therapeutic targets, and highlights potential metabolism-related targets for therapeutic intervention in HCC.
HES V2.0 outperforms GALAD for detection of HCC: A phase 3 biomarker study in the United States
Authors: Hashem B. El-Serag, Qingchun Jin, Nabihah Tayob, Emad Salem, Michelle Luster, Abeer Alsarraj, Saira Khaderi, Amit G. Singal, Jorge A. Marrero, Sumeet K. Asrani, Fasiha Kanwal
Journal: Hepatology (2024)

The original hepatocellular carcinoma early detection screening (HES) score, which combines alpha-fetoprotein (AFP) with age, alanine aminotransferase, and platelets, has better performance than AFP alone for early HCC detection. We have developed HES V2.0 by adding AFP-L3 and des-gamma-carboxy prothrombin to the score and compared its performance to GALAD and ASAP scores among patients with cirrhosis.
Nab-paclitaxel, cisplatin, and capecitabine versus cisplatin and gemcitabine as first line chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma: randomised phase 3 clinical trial
Authors: Guo-Ying Liu, Yan-Fang Ye, Yao-Fei Jiang, Gina Jinna Chen, Wei-Xiong Xia, Yi-Sheng Huang, Tian-Sheng Gao, Yi-Min Liu, Ya-Ting Hou, Jian-Fei Li, Jia-Hao Liu, Nian Lu, Chang-Long Chen, Liang-Ru Ke, Hu Liang, Wei-Xin Bei, Wang-Zhong Li, Shu-Hui Dong, Qin Liu, Changqing Xie, He-Rui Yao, Yan-Qun Xiang
Journal: BMJ (2024)

To compare the effectiveness and safety of nab-paclitaxel, cisplatin, and capecitabine (nab-TPC) with gemcitabine and cisplatin as an alternative first line treatment option for recurrent or metastatic nasopharyngeal carcinoma. Phase 3, open label, multicentre, randomised trial. Four hospitals located in China between September 2019 and August 2022. Adults (≥18 years) with recurrent or metastatic nasopharyngeal carcinoma. Patients were randomised in a 1:1 ratio to treatment with either nab-paclitaxel (200 g/m2 on day 1), cisplatin (60 mg/m2 on day 1), and capecitabine (1000 mg/m2 twice on days 1-14) or gemcitabine (1 g/m2 on days 1 and 8) and cisplatin (80 mg/m2 on day 1). Progression-free survival was evaluated by the independent review committee as the primary endpoint in the intention-to-treat population. The median follow-up was 15.8 months in the prespecified interim analysis (31 October 2022). As assessed by the independent review committee, the median progression-free survival was 11.3 (95% confidence interval 9.7 to 12.9) months in the nab-TPC cohort compared with 7.7 (6.5 to 9.0) months in the gemcitabine and cisplatin cohort. The hazard ratio was 0.43 (95% confidence interval 0.25 to 0.73; P=0.002). The objective response rate in the nab-TPC cohort was 83% (34/41) versus 63% (25/40) in the gemcitabine and cisplatin cohort (P=0.05), and the duration of response was 10.8 months in the nab-TPC cohort compared with 6.9 months in the gemcitabine and cisplatin cohort (P=0.009). Treatment related grade 3 or 4 adverse events, including leukopenia (4/41 (10%) v 13/40 (33%); P=0.02), neutropenia (6/41 (15%) v 16/40 (40%); P=0.01), and anaemia (1/41 (2%) v 8/40 (20%); P=0.01), were higher in the gemcitabine and cisplatin cohort than in the nab-TPC cohort. No deaths related to treatment occurred in either treatment group. Survival and long term toxicity are still being evaluated with longer follow-up. The nab-TPC regimen showed a superior antitumoural efficacy and favourable safety profile compared with gemcitabine and cisplatin for recurrent or metastatic nasopharyngeal carcinoma. Nab-TPC should be considered the standard first line treatment for recurrent or metastatic nasopharyngeal carcinoma. Longer follow-up is needed to confirm the benefits for overall survival. Chinese Clinical Trial Registry ChiCTR1900027112.
Prevalence and prognosis of aortic valve diseases in patients hospitalized with heart failure with mildly reduced ejection fraction
Authors: Tobias Schupp, Noah Abel, Moritz Schmidberger, Mila Kathrin Höpfner, Alexander Schmitt, Marielen Reinhardt, Jan Forner, Felix Lau, Muharrem Akin, Jonas Rusnak, Ibrahim Akin, Michael Behnes
Journal: European Journal of Heart Failure (2024)

Abstract Aims Data regarding the characterization and outcomes of patients with heart failure (HF) with mildly reduced ejection fraction (HFmrEF) is scarce. This study investigates the characteristics and prognostic impact of native aortic valve diseases (AVD) in patients with HFmrEF. Methods and results Consecutive patients hospitalized with HFmrEF (i.e. left ventricular ejection fraction 41–49% and signs and/or symptoms of HF) were retrospectively included at one institution from 2016 to 2022. The prognostic impact of native aortic valve stenosis (AS), aortic valve regurgitation (AR) and mixed AVD (MAVD) was investigated for the primary endpoint of long‐term all‐cause mortality during a median follow‐up of 30 months. Kaplan–Meier, univariable and multivariable Cox proportional analyses were applied. From a total of 2106 patients hospitalized with HFmrEF, the prevalence of AS and AR was 16.5% and 31.2%, respectively (MAVD 7.8%). The presence of moderate/severe AS was associated with a higher risk of long‐term all‐cause mortality (44.8% vs. 28.7%; p = 0.001) and HF‐related rehospitalization (18.6% vs. 12.0%; p = 0.001), even after multivariable adjustment (mortality: hazard ratio [HR] 1.320; 95% confidence interval [CI] 1.035–1.684; p = 0.025; HF‐related rehospitalization: HR 1.570; 95% CI 1.101–2.241; p = 0.013). Interestingly, even mild AS was associated with increased risk of long‐term all‐cause mortality compared to patients without AS (HR 1.477; 95% CI 1.101–1.982; p = 0.009). In contrast, the presence of AR was not associated with long‐term outcomes after multivariable adjustment. Conclusions The presence of AS, but not AR, was independently associated with increased risk of all‐cause mortality and HF‐related rehospitalization in patients with HFmrEF. Even milder stages of AS were associated with impaired prognosis.
Characterization of serum phosphate levels over time with intravenous ferric carboxymaltose versus placebo as treatment for heart failure with reduced ejection fraction and iron deficiency: An exploratory prospective substudy from <scp>HEART</scp>‐<scp>FID</scp>
Authors: Nina Nouhravesh, Jyotsna Garg, Frank W. Rockhold, Carmine G. De Pasquale, Eileen O'Meara, Gregory D. Lewis, Javed Butler, Josephine Harrington, Justin A. Ezekowitz, Piotr Ponikowski, Richard W. Troughton, Yee Weng Wong, Nicole Blackman, Syed Numan, Robert Adamczyk, Adrian F. Hernandez, Robert J. Mentz
Journal: European Journal of Heart Failure (2024)
Bioinspired Nano‐Photosensitizer‐Activated Caspase‐3/GSDME Pathway Induces Pyroptosis in Lung Cancer Cells
Authors: Min Gao, Qiuting Sun, Huiru Zhang, Mengyu Liu, Rui Peng, Weiji Qin, Qian Wang, Tianhao Yang, Man Zhou, Xiaoyan He, Gengyun Sun
Journal: Advanced Healthcare Materials (2024)

Noninflammatory apoptosis is transformed into inflammatory pyroptosis by activating caspase-3 to lyse gasdermin E (GSDME), and this process can be used as an effective therapeutic strategy. Thus, a selective and powerful inducer of activated caspase-3 plays a vital role in pyroptosis-based cancer therapy. Herein, a human cell membrane vesicle-based nanoplatform (HCNP) is designed for photodynamic therapy (PDT). HCNP is modified with vesicular stomatitis virus G-protein (VSVG) to anchor nano-photosensitizers on the tumor cell membrane. Photosensitizers are bonded to HCNP by clicking chemical reaction as pyroptosis inducers. The results show that HCNP effectively disrupts the mitochondrial function of cells by generating reactive oxygen species (ROS) upon laser irradiation; concomitantly, GSDME is cleaved by activated caspase-3 and promotes pyroptosis of lung cancer cells. Here an effective intervention strategy is proposed to induce pyroptosis based on light-activated PDT.
Adaptation to fluctuating temperatures across life stages in endotherms
Authors: Mads F. Schou, Charlie K. Cornwallis
Journal: Trends in Ecology & Evolution (2024)

Accelerating rates of climate change have intensified research on thermal adaptation. Increasing temperature fluctuations, a prominent feature of climate change, means that the persistence of many species depends on both heat and cold tolerance across the entire life cycle. In endotherms, research has focused on specific life stages, with changes in thermoregulation across life rarely being examined. Consequently, there is a need to (i) analyse how heat and cold tolerance mechanisms coevolve, and (ii) test whether antagonistic effects between heat and cold tolerance across different life stages limit thermal adaptation. Information on genes influencing heat and cold tolerance and how they are expressed through life will enable more accurate modelling of species vulnerabilities to future climatic volatility.
Erratum to “An update on clinical presentation and responses to therapy of patients with hereditary hypophosphatemic rickets with hypercalciuria (HHRH).” Kidney International 2023;105:1058–1076
Authors: Zewu Zhu, Bryan Bo-Ran Ho, Alyssa Chen, James Amrhein, Andreea Apetrei, Thomas Oliver Carpenter, Marise Lazaretti-Castro, Juan Manuel Colazo, Kathryn McCrystal Dahir, Michaela Geßner, Evgenia Gurevich, Cathrine Alsaker Heier, Jill Hickman Simmons, Tracy Earl Hunley, Bernd Hoppe, Christina Jacobsen, Anne Kouri, Nina Ma, Sachin Majumdar, Arnaud Molin, Natalie Nokoff, Susan M Ott, Helena Gil Peña, Fernando Santos, Peter Tebben, Lisa Swartz Topor, Yanhong Deng, Clemens Bergwitz
Journal: Kidney International (2024)
Efficacy and Safety of LX9211 for Relief of Diabetic Peripheral Neuropathic Pain (RELIEF-DPN 1): Results of a Double-Blind, Randomized, Placebo-Controlled, Proof-of-Concept Study
Authors: Rodica Pop-Busui, Anand Patel, Christine Nai-Mei Sang, Phillip L. Banks, Phillip F. Pierce, Franklin Sun, Craig Granowitz, Suma Gopinathan
Journal: Diabetes Care (2024)

OBJECTIVE To evaluate the efficacy of LX9211 in reducing pain related to diabetic peripheral neuropathy. RESEARCH DESIGN AND METHODS In this double-blind, multicenter, proof-of-concept trial, 319 individuals with diabetic peripheral neuropathic pain (DPNP) were randomized (1:1:1) to LX9211 10 mg (n = 106), LX9211 20 mg (n = 106), or matching placebo (n = 107), administered once daily for 6 weeks. DPNP was rated daily with an 11-point numerical rating scale. The primary end point was change from baseline to week 6 in the average daily pain score. The difference between each LX9211 group and placebo was evaluated with mixed-model repeated-measures analysis. RESULTS For those on low-dose LX9211 the primary efficacy end point was achieved: −1.39 vs. −0.72 points for placebo, least squares mean (SE) difference −0.67 (0.249), 95% CI −1.16 to −0.18, P = 0.007; results for high-dose LX9211 demonstrated improvement in pain severity versus placebo (−1.27 vs. −0.72 points, respectively), but the between-group LS mean difference did not reach the prespecified statistical significance (−0.55 [0.254], 95% CI −1.06 to −0.05, P = 0.030). Treatment benefit was observed beginning at week 1 and maintained thereafter. Results for LX9211 also demonstrated improvement in several patient-reported secondary outcomes. Most common adverse events (AEs) were dizziness, nausea, and headache. More participants treated with LX9211 (20 mg, n = 28 [26.4%]; 10 mg, 17 [16.0%]) than placebo (3 [2.8%]) discontinued study drug prematurely due to AEs; serious AEs were uncommon (2 [1.9%], 0, and 1 [0.9%], respectively). CONCLUSIONS These preliminary findings of improvement in DPNP with LX9211 support further investigation in larger trials.
Penetrative Ionic Organic Molecular Cage Nanozyme for the Targeted Treatment of Keratomycosis
Authors: Hongwei Wang, Fangying Song, Xia Qi, Xiaoyu Zhang, Li Ma, Depeng Shi, Xiaofei Bai, Shengqian Dou, Qingjun Zhou, Chao Wei, Bi Ning Zhang, Ting Wang, Weiyun Shi
Journal: Advanced Healthcare Materials (2024)

Keratomycosis, caused by pathogenic fungi, is an intractable blinding eye disease. Corneal penetration is an essential requirement for conventional antifungal medications to address keratomycosis. Due to the distinctive anatomical and physiological structure of the cornea, the therapeutic efficacy is hampered by the inadequate penetration capacity. Despite the emergence of diverse antifungal drug delivery systems and advanced antifungal nanomaterials, it has remained challenging to achieve corneal penetration over the past decade. This study fabricates a penetrative ionic organic molecular cage-based nanozyme (OMCzyme) for treating keratomycosis. The synthesis of OMCzyme involved two steps. Initially, the ionic OMC is synthesized by a [2+3] cycloimination reaction of triformylphloroglucinol and 2,3-diaminopropionic acid. Subsequently, OMCzyme is fabricated by coordination of Fe
Corrigendum to “Phosphoglycerate mutase 5 initiates inflammation in acute kidney injury by triggering mitochondrial DNA release by dephosphorylating the pro-apoptotic protein Bax.” Kidney International 2023;103:115–133
Authors: Jingyao Li, Xi'ang Sun, Ninghao Yang, Jiayun Ni, Hongyan Xie, Hengjiang Guo, Xin Wang, Li Zhou, Jun Liu, Sijia Chen, Xiaoxia Wang, Yingying Zhang, Chen Yu, Wei Zhang, Limin Lu
Journal: Kidney International (2024)
Mental health and wellbeing outcomes associated with social, medical, and legal gender affirmation among trans young people in Australia
Authors: Ruby Grant, Natalie Amos, Ashleigh Lin, Teddy Cook, Adam O. Hill, Ken Pang, Rachel S. Skinner, Marina Carman, Adam Bourne
Journal: International Journal of Transgender Health (2024)

Background Gender affirmation is known to improve mental health among trans adults, but its impact on young people has been questioned. This study examined the mental health outcomes associated with social, medical, and legal gender affirmation among trans young people in Australia.
Principal component-based clinical aging clocks identify signatures of healthy aging and targets for clinical intervention
Authors: Sheng Fong, Kamil Pabis, Djakim Latumalea, Nomuundari Dugersuren, Maximilian Unfried, Nicholas Tolwinski, Brian Kennedy, Jan Gruber
Journal: Nature Aging (2024)

Abstract Clocks that measure biological age should predict all-cause mortality and give rise to actionable insights to promote healthy aging. Here we applied dimensionality reduction by principal component analysis to clinical data to generate a clinical aging clock (PCAge) identifying signatures (principal components) separating healthy and unhealthy aging trajectories. We found signatures of metabolic dysregulation, cardiac and renal dysfunction and inflammation that predict unsuccessful aging, and we demonstrate that these processes can be impacted using well-established drug interventions. Furthermore, we generated a streamlined aging clock (LinAge), based directly on PCAge, which maintains equivalent predictive power but relies on substantially fewer features. Finally, we demonstrate that our approach can be tailored to individual datasets, by re-training a custom clinical clock (CALinAge), for use in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) study of caloric restriction. Our analysis of CALERIE participants suggests that 2 years of mild caloric restriction significantly reduces biological age. Altogether, we demonstrate that this dimensionality reduction approach, through integrating different biological markers, can provide targets for preventative medicine and the promotion of healthy aging.
Entrectinib in ROS1-positive advanced non-small cell lung cancer: the phase 2/3 BFAST trial
Authors: Solange Peters, Shirish M. Gadgeel, Tony Mok, Ernest Nadal, Saadettin Kilickap, Aurélie Swalduz, Jacques Cadranel, Shunichi Sugawara, Chao-Hua Chiu, Chong-Jen Yu, Mor Moskovitz, Tomohiro Tanaka, Rhea Nersesian, Sarah M. Shagan, Margaret Maclennan, Michael Mathisen, Vijay Bhagawati-Prasad, Cheick Diarra, Zoe June Assaf, Venice Archer, Rafal Dziadziuszko
Journal: Nature Medicine (2024)

Although comprehensive biomarker testing is recommended for all patients with advanced/metastatic non-small cell lung cancer (NSCLC) before initiation of first-line treatment, tissue availability can limit testing. Genomic testing in liquid biopsies can be utilized to overcome the inherent limitations of tissue sampling and identify the most appropriate biomarker-informed treatment option for patients. The Blood First Assay Screening Trial is a global, open-label, multicohort trial that evaluates the efficacy and safety of multiple therapies in patients with advanced/metastatic NSCLC and targetable alterations identified by liquid biopsy. We present data from Cohort D (ROS1-positive). Patients ≥18 years of age with stage IIIB/IV, ROS1-positive NSCLC detected by liquid biopsies received entrectinib 600 mg daily. At data cutoff (November 2021), 55 patients were enrolled and 54 had measurable disease. Cohort D met its primary endpoint: the confirmed objective response rate (ORR) by investigator was 81.5%, which was consistent with the ORR from the integrated analysis of entrectinib (investigator-assessed ORR, 73.4%; data cutoff May 2019, ≥12 months of follow-up). The safety profile of entrectinib was consistent with previous reports. These results demonstrate consistency with those from the integrated analysis of entrectinib in patients with ROS1-positive NSCLC identified by tissue-based testing, and support the clinical value of liquid biopsies to inform clinical decision-making. The integration of liquid biopsies into clinical practice provides patients with a less invasive diagnostic method than tissue-based testing and has faster turnaround times that may expedite the reaching of clinical decisions in the advanced/metastatic NSCLC setting. ClinicalTrials.gov registration: NCT03178552 .
Stem-like T cells are associated with the pathogenesis of ulcerative colitis in humans
Authors: Yingcong Li, Ciro Ramírez-Suástegui, Richard Harris, Francisco Emmanuel Castañeda-Castro, Gabriel Ascui, Tamara Pérez-Jeldres, Alejandro Diaz, Carla Morong, Daniel A. Giles, Jiani Chai, Gregory Seumois, Tilman Sanchez-Elsner, Fraser Cummings, Mitchell Kronenberg, Pandurangan Vijayanand
Journal: Nature Immunology (2024)
A pathologist–AI collaboration framework for enhancing diagnostic accuracies and efficiencies
Authors: Zhi Huang, Eric Yang, Jeanne Shen, Dita Gratzinger, Frederick Eyerer, Brooke Liang, Jeffrey Nirschl, David Bingham, Alex M. Dussaq, Christian Kunder, Rebecca Rojansky, Aubre Gilbert, Alexandra L. Chang-Graham, Brooke E. Howitt, Ying Liu, Emily E. Ryan, Troy B. Tenney, Xiaoming Zhang, Ann Folkins, Edward J. Fox, Kathleen S. Montine, Thomas J. Montine, James Zou
Journal: Nature Biomedical Engineering (2024)
Bidirectional linkage of DNA barcodes for the multiplexed mapping of higher-order protein interactions in cells
Authors: Yu Liu, Noah R. Sundah, Nicholas R. Y. Ho, Wan Xiang Shen, Yun Xu, Auginia Natalia, Zhonglang Yu, Ju Ee Seet, Ching Wan Chan, Tze Ping Loh, Brian Y. Lim, Huilin Shao
Journal: Nature Biomedical Engineering (2024)
The multifaceted functions of DNA‐PKcs: implications for the therapy of human diseases
Authors: Jinghong Wu, Liwei Song, Mingjun Lu, Qing Gao, Shaofa Xu, Ping‐Kun Zhou, Teng Ma
Journal: MedComm (2024)

The DNA-dependent protein kinase (DNA-PK), catalytic subunit, also known as DNA-PKcs, is complexed with the heterodimer Ku70/Ku80 to form DNA-PK holoenzyme, which is well recognized as initiator in the nonhomologous end joining (NHEJ) repair after double strand break (DSB). During NHEJ, DNA-PKcs is essential for both DNA end processing and end joining. Besides its classical function in DSB repair, DNA-PKcs also shows multifaceted functions in various biological activities such as class switch recombination (CSR) and variable (V) diversity (D) joining (J) recombination in B/T lymphocytes development, innate immunity through cGAS-STING pathway, transcription, alternative splicing, and so on, which are dependent on its function in NHEJ or not. Moreover, DNA-PKcs deficiency has been proven to be related with human diseases such as neurological pathogenesis, cancer, immunological disorder, and so on through different mechanisms. Therefore, it is imperative to summarize the latest findings about DNA-PKcs and diseases for better targeting DNA-PKcs, which have shown efficacy in cancer treatment in preclinical models. Here, we discuss the multifaceted roles of DNA-PKcs in human diseases, meanwhile, we discuss the progresses of DNA-PKcs inhibitors and their potential in clinical trials. The most updated review about DNA-PKcs will hopefully provide insights and ideas to understand DNA-PKcs associated diseases.