tbuckley/cabot-search huggingface dataset:
Phase Ib/IIa randomized study of heterologous ChAdOx1-HBV/MVA-HBV therapeutic vaccination (VTP-300) as monotherapy and combined with low-dose nivolumab in virally-suppressed patients with CHB
Authors: Won Young Tak, Wan-Lobg Chuang, Chi-Yi Chen, Kuo-Chih Tseng, Young-Suk Lim, Gin-Ho Lo, Jeong Heo, Kaushik Agarwal, Louise Bussey, Sui Lynn Teoh, A. Tria, Anthony Brown, Katie Anderson, Antonella Vardeu, Susanne O’Brien, Jakub Kopycinski, Radka Kolenovska, Ellie Barnes, Thomas Evans
Journal: Journal of Hepatology (2024)
Current state and novel outlook on prevention and treatment of rising antibiotic resistance in urinary tract infections
Authors: Emina K. Sher, Amina Džidić-Krivić, Ana Sesar, Esma K. Farhat, Amila Čeliković, Merima Beća-Zećo, Emma Pinjic, Farooq Sher
Journal: Pharmacology & Therapeutics (2024)
Quantifying impairment and disease severity using AI models trained on healthy subjects
Authors: Boyang Yu, Aakash Kaku, Kangning Liu, Avinash Parnandi, Emily Fokas, Anita Venkatesan, Natasha Pandit, Rajesh Ranganath, Heidi Schambra, Carlos Fernandez-Granda
Journal: npj Digital Medicine (2024)

Abstract Automatic assessment of impairment and disease severity is a key challenge in data-driven medicine. We propose a framework to address this challenge, which leverages AI models trained exclusively on healthy individuals. The COnfidence-Based chaRacterization of Anomalies (COBRA) score exploits the decrease in confidence of these models when presented with impaired or diseased patients to quantify their deviation from the healthy population. We applied the COBRA score to address a key limitation of current clinical evaluation of upper-body impairment in stroke patients. The gold-standard Fugl-Meyer Assessment (FMA) requires in-person administration by a trained assessor for 30-45 minutes, which restricts monitoring frequency and precludes physicians from adapting rehabilitation protocols to the progress of each patient. The COBRA score, computed automatically in under one minute, is shown to be strongly correlated with the FMA on an independent test cohort for two different data modalities: wearable sensors ( ρ = 0.814, 95% CI [0.700,0.888]) and video ( ρ = 0.736, 95% C.I [0.584, 0.838]). To demonstrate the generalizability of the approach to other conditions, the COBRA score was also applied to quantify severity of knee osteoarthritis from magnetic-resonance imaging scans, again achieving significant correlation with an independent clinical assessment ( ρ = 0.644, 95% C.I [0.585,0.696]).
DCCAT: Dual-Coordinate Cross-Attention Transformer for thrombus segmentation on coronary OCT
Authors: Miao Chu, Giovanni Luigi De Maria, Ruobing Dai, Stefano Benenati, Wei Yu, Jiaxin Zhong, Rafail Kotronias, Jason Walsh, Stefano Andreaggi, Vittorio Zuccarelli, Jason Chai, Keith Channon, Adrian Banning, Shengxian Tu
Journal: Medical Image Analysis (2024)
Artificial intelligence in Parkinson's disease: Early detection and diagnostic advancements
Authors: Aananya Reddy, Ruhananhad P. Reddy, Aryan Kia Roghani, Ricardo Isaiah Garcia, Sachi Khemka, Vasanthkumar Pattoor, Michael Jacob, P. Hemachandra Reddy, Ujala Sehar
Journal: Ageing Research Reviews (2024)
Traumatic brain injury in elderly population: a global systematic review and meta-analysis of in-hospital mortality and risk factors among 2.22 million individuals
Authors: Zixuan Ma, Zhenghui He, Zhifan Li, Ru Gong, Jiyuan Hui, Weiji Weng, Xiang Wu, Chun Yang, Jiyao Jiang, Li Xie, Junfeng Feng
Journal: Ageing Research Reviews (2024)
Zinc oxide nanoparticles with catalase-like nanozyme activity and near-infrared light response: A combination of effective photodynamic therapy, autophagy, ferroptosis, and antitumor immunity
Authors: Jingru Wang, Man Liu, Jingwen Wang, Zhuoyue Li, Zhenhan Feng, Meiqi Xu, Hui Wang, Hui Li, Zhantao Li, Jianming Yu, Junwei Liu, Qingchao Wei, Shuang Zhang, Xuan Zhang
Journal: Acta Pharmaceutica Sinica B (2024)

We prepared biocompatible and environment-friendly zinc oxide nanoparticles (ZnO NPs) with upconversion properties and catalase-like nanozyme activity. Photodynamic therapy (PDT) application is severely limited by the poor penetration of UV-Visible light and a hypoxic tumor environment. Here, we used ZnO NPs as a carrier for the photosensitizer chlorin e6 (Ce6) to construct zinc oxide-chlorin e6 nanoparticles (ZnO-Ce6 NPs), simultaneously addressing both problems. In terms of penetration, ZnO NPs convert 808 nm near-infrared light into 401 nm visible light to excite Ce6, achieving deep-penetrating photodynamic therapy under long-wavelength light. Interestingly, the ability to emit short-wavelength light under long-wavelength light is usually observed in upconversion nanoparticles. As nanozymes, ZnO NPs can catalyze the decomposition of hydrogen peroxide in tumors, providing oxygen for photodynamic action and relieving hypoxia. The enhanced photodynamic action produces a large amount of reactive oxygen species, which overactivate autophagy and trigger immunogenic cell death (ICD), leading to antitumor immunotherapy. In addition, even in the absence of light, ZnO and ZnO-Ce6 NPs can induce ferroptosis of tumor cells and exert antitumor effects.
Clonal Lineage Tracing with Somatic Delivery of Recordable Barcodes Reveals Migration Histories of Metastatic Prostate Cancer
Authors: Ryan N. Serio, Armin Scheben, Billy Lu, Domenic V. Gargiulo, Lucrezia Patruno, Caroline L. Buckholtz, Ryan J. Chaffee, Megan C. Jibilian, Steven G. Persaud, Stephen J. Staklinski, Rebecca Hassett, Lise M. Brault, Daniele Ramazzotti, Christopher E. Barbieri, Adam C. Siepel, Dawid G. Nowak
Journal: Cancer Discovery (2024)

The patterns by which primary tumors spread to metastatic sites remain poorly understood. Here, we define patterns of metastatic seeding in prostate cancer using a novel injection-based mouse model-EvoCaP (Evolution in Cancer of the Prostate), featuring aggressive metastatic cancer to bone, liver, lungs, and lymph nodes. To define migration histories between primary and metastatic sites, we used our EvoTraceR pipeline to track distinct tumor clones containing recordable barcodes. We detected widespread intratumoral heterogeneity from the primary tumor in metastatic seeding, with few clonal populations instigating most migration. Metastasis-to-metastasis seeding was uncommon, as most cells remained confined within the tissue. Migration patterns in our model were congruent with human prostate cancer seeding topologies. Our findings support the view of metastatic prostate cancer as a systemic disease driven by waves of aggressive clones expanding their niche, infrequently overcoming constraints that otherwise keep them confined in the primary or metastatic site. Significance: Defining the kinetics of prostate cancer metastasis is critical for developing novel therapeutic strategies. This study uses CRISPR/Cas9-based barcoding technology to accurately define tumor clonal patterns and routes of migration in a novel somatically engineered mouse model (EvoCaP) that recapitulates human prostate cancer using an in-house developed analytical pipeline (EvoTraceR).
Plasma Metabolomics Identifies Key Metabolites and Improves Prediction of Diabetic Retinopathy
Authors: Shaopeng Yang, Riqian Liu, Zhuoyao Xin, Ziyu Zhu, Jiaqing Chu, Pingting Zhong, Zhuoting Zhu, Xianwen Shang, Wenyong Huang, Lei Zhang, Mingguang He, Wei Wang
Journal: Ophthalmology (2024)
Availability of lasers and hands-on training in cosmetic dermatology in residency
Authors: Bianca Y. Kang, Erik J. Stratman, Jenny C. Hu, Rachel Elsanadi, Tanya Greywal, Kristen M. Kelly, Arisa Ortiz, Sami K. Saikaly, Kathleen C. Suozzi, Diana Bolotin, Kira Minkis, Murad Alam, Diana D. Antonovich, Anna Bar, Alison Boucher, Maggie L. Chow, M. Laurin Council, Loma Dave, Min Deng, Milad Eshaq, Ronda S. Farah, Erica Ghareeb, Carolyn Hardin Robinson, Deirdre Hooper, Elika Hoss, Farhana Ikmal Hisham, Jayne Joo, Erica B. Kelly, Nour Kibbi, Lauren C.S. Kole, A. Shadi Kourosh, Helena Kuhn, Jessica G. Labadie, Naomi Lawrence, Yakir S. Levin, Janiene Luke, Umer Nadir, Zeena Y. Nawas, Jeffrey S. Orringer, Michelle V. Pearlstein, Vesna Petronic-Rosic, Jared E. Roberts, Olivia L. Schenck, Cynthia A. Schlick, Kalee Shah, Ladan Shahabi, Amanda K. Suggs, Leila Tolaymat, Neelam A. Vashi, Kimberley H.M. Ward, Saranya P. Wyles, Michael Yi, Simon S. Yoo
Journal: Journal of the American Academy of Dermatology (2024)
Assessment of diagnostic delay, morbidity, and mortality outcomes in 302 calciphylaxis patients over a 17-year period: A retrospective cohort study
Authors: Alice J. Tan, Joyce Xia, Colleen M. Glennon, Joseph J. Locascio, Colleen K. Gabel, Emily D. Nguyen, Sidharth Chand, Renajd Rrapi, Allison S. Dobry, Anna Cristina Garza-Mayers, Lauren N. Ko, Radhika Shah, Jessica St John, Sagar U. Nigwekar, Daniela Kroshinsky
Journal: Journal of the American Academy of Dermatology (2024)
Liposome‐based in situ antigen‐modification strategy for “universal” T‐cell‐receptor engineered T cell in cancer immunotherapy
Authors: Qin Wang, Rui Peng, Haoyue Qi, Ruihan Xu, Wanmin Liu, Fanyan Meng, Shiyao Du, Lixia Yu, Jia Wei, Fangcen Liu, Rutian Li
Journal: MedComm (2024)

Abstract T‐cell receptor (TCR) engineered T‐cell therapy, unlike chimeric antigen receptor T‐cell therapy, relies on the inherent ability of TCRs to detect a wider variety of antigenic epitopes, such as protein fragments found internally or externally on cells. Hence, TCR‐T‐cell therapy offers broader possibilities for treating solid tumors. However, because of the complicated process of identifying specific antigenic peptides, their clinical application still encounters significant challenges. Thus, we aimed to establish a novel “universal” TCR‐T “artificial antigen expression” technique that involves the delivery of the antigen to tumor cells using DSPE‐PEG‐NY‐ESO‐1 157‐165 liposomes (NY‐ESO‐1 Lips) to express TCR‐T‐cell‐specific recognition targets. In vitro as well as in vivo studies revealed that they could accumulate efficiently in the tumor area and deliver target antigens to activate the tumor‐specific cytotoxic T‐cell immune response. NY‐ESO‐1 TCR‐T therapy, when used in combination, dramatically curbed tumor progression and extended the longevity of mice. Additionally, PD‐1 blockage enhanced the therapeutic effect of the aforementioned therapy. In conclusion, NY‐ESO‐1 Lips “cursed” tumor cells by enabling antigenic target expression on their surface. This innovative technique presents a groundbreaking approach for the widespread utilization of TCR‐T in solid tumor treatment.
Nor-LAAM loaded PLGA microparticles for treating opioid use disorder
Authors: Diane Ingabire, Chaolong Qin, Tuo Meng, Aji Alex Moothendathu Raynold, Hadi Sudarjat, E. Andrew Townsend, Rudra Pangeni, Sagun Poudel, Michelle Arriaga, Long Zhao, Woon N. Chow, Matthew Banks, Qingguo Xu
Journal: Journal of Controlled Release (2024)
Dual-reactive single-chain polymer nanoparticles for orthogonal functionalization through active ester and click chemistry
Authors: Jan-Willem D. Paats, Naomi M. Hamelmann, Jos M.J. Paulusse
Journal: Journal of Controlled Release (2024)

Glucose has been extensively studied as a targeting ligand on nanoparticles for biomedical nanoparticles. A promising nanocarrier platform are single-chain polymer nanoparticles (SCNPs). SCNPs are well-defined 5-20 nm semi-flexible nano-objects, formed by intramolecularly crosslinked linear polymers. Functionality can be incorporated by introducing labile pentafluorophenyl (PFP) esters in the polymer backbone, which can be readily substituted by functional amine-ligands. However, not all ligands are compatible with PFP-chemistry, requiring different ligation strategies for increasing versatility of surface functionalization. Here, we combine active PFP-ester chemistry with copper(I)-catalyzed azide alkyne cycloaddition (CuAAC) click chemistry to yield dual-reactive SCNPs. First, the SCNPs are functionalized with increasing amounts of 1-amino-3-butyne groups through PFP-chemistry, leading to a range of butyne-SCNPs with increasing terminal alkyne-density. Subsequently, 3-azido-propylglucose is conjugated through the glucose C1- or C6-position by CuAAC click chemistry, yielding two sets of glyco-SCNPs. Cellular uptake is evaluated in HeLa cancer cells, revealing increased uptake upon higher glucose-surface density, with no apparent positional dependance. The general conjugation strategy proposed here can be readily extended to incorporate a wide variety of functional molecules to create vast libraries of multifunctional SCNPs.
Long-term outcome following liver transplantation of patients with ACLF grade 3
Authors: Florent Artru, Sophie-Caroline Sacleux, Jose Ursic-Bedoya, Line Carole Ntandja Wandji, Alina Lutu, Sebastien L’Hermite, Clementine Levy, Marion Khaldi, Eric Levesque, Sebastien Dharancy, Emmanuel Boleslawski, Gilles Lebuffe, Charles Le Goffic, Philippe Ichai, Audrey Coilly, Eleonora De Martin, Eric Vibert, Magdalena Meszaros, Astrid Herrerro, Clement Monet, Samir Jaber, Didier Samuel, Philippe Mathurin, Julien Labreuche, Georges-Philippe Pageaux, Faouzi Saliba, Alexandre Louvet
Journal: Journal of Hepatology (2024)
TaqTth-hpRNA: a novel compact RNA-targeting tool for specific silencing of pathogenic mRNA
Authors: Chong Xu, Jiyanuo Cao, Huanran Qiang, Yu Liu, Jialin Wu, Qiudan Luo, Meng Wan, Yujie Wang, Peiliang Wang, Qian Cheng, Guohua Zhou, Jian Sima, Yongjian Guo, Shu Xu
Journal: Genome biology (2024)

Abstract Pathogenic allele silencing is a promising treatment for genetic hereditary diseases. Here, we develop an RNA-cleaving tool, TaqTth-hpRNA, consisting of a small, chimeric TaqTth, and a hairpin RNA guiding probe. With a minimal flanking sequence-motif requirement, in vitro and in vivo studies show TaqTth-hpRNA cleaves RNA efficiently and specifically. In an Alzheimer’s disease model, we demonstrate silencing of mutant APP swe mRNA without altering the wild-type APP mRNA. Notably, due to the compact size of TaqTth, we are able to combine with APOE2 overexpression in a single AAV vector, which results in stronger inhibition of pathologies.
Comprehensive assessment of machine learning methods for diagnosing gastrointestinal diseases through whole metagenome sequencing data
Authors: Sungho Lee, Insuk Lee
Journal: Gut Microbes (2024)

The gut microbiome, linked significantly to host diseases, offers potential for disease diagnosis through machine learning (ML) pipelines. These pipelines, crucial in modeling diseases using high-dimensional microbiome data, involve selecting profile modalities, data preprocessing techniques, and classification algorithms, each impacting the model accuracy and generalizability. Despite whole metagenome shotgun sequencing (WMS) gaining popularity for human gut microbiome profiling, a consensus on the optimal methods for ML pipelines in disease diagnosis using WMS data remains elusive. Addressing this gap, we comprehensively evaluated ML methods for diagnosing Crohn's disease and colorectal cancer, using 2,553 fecal WMS samples from 21 case-control studies. Our study uncovered crucial insights: gut-specific, species-level taxonomic features proved to be the most effective for profiling; batch correction was not consistently beneficial for model performance; compositional data transformations markedly improved the models; and while nonlinear ensemble classification algorithms typically offered superior performance, linear models with proper regularization were found to be more effective for diseases that are linearly separable based on microbiome data. An optimal ML pipeline, integrating the most effective methods, was validated for generalizability using holdout data. This research offers practical guidelines for constructing reliable disease diagnostic ML models with fecal WMS data.
Quinic acid alleviates high-fat diet-induced neuroinflammation by inhibiting DR3/IKK/NF-κB signaling via gut microbial tryptophan metabolites
Authors: Sen Li, Yuwei Cai, Tong Guan, Yu Zhang, Kai Huang, Ze Zhang, Wangqing Cao, Xiao Guan
Journal: Gut Microbes (2024)

With the increasing of aging population and the consumption of high-fat diets (HFD), the incidence of Alzheimer's disease (AD) has skyrocketed. Natural antioxidants show promising potential in the prevention of AD, as oxidative stress and neuroinflammation are two hallmarks of AD pathogenesis. Here, we showed that quinic acid (QA), a polyphenol derived from millet, significantly decreased HFD-induced brain oxidative stress and neuroinflammation and the levels of Aβ and p-Tau. Examination of gut microbiota suggested the improvement of the composition of gut microbiota in HFD mice after QA treatment. Metabolomic analysis showed significant increase of gut microbial tryptophan metabolites indole-3-acetic acid (IAA) and kynurenic acid (KYNA) by QA. In addition, IAA and KYNA showed negative correlation with pro-inflammatory factors and AD indicators. Further experiments on HFD mice proved that IAA and KYNA could reproduce the effects of QA that suppress brain oxidative stress and inflammation and decrease the levels of of Aβ and p-Tau. Transcriptomics analysis of brain after IAA administration revealed the inhibition of DR3/IKK/NF-κB signaling pathway by IAA. In conclusion, this study demonstrated that QA could counteract HFD-induced brain oxidative stress and neuroinflammation by regulating inflammatory DR3/IKK/NF-κB signaling pathway via gut microbial tryptophan metabolites.
A powerful machine learning approach to identify interactions of differentially abundant gut microbial subsets in patients with metastatic and non-metastatic pancreatic cancer
Authors: Annacandida Villani, Andrea Fontana, Concetta Panebianco, Carmelapia Ferro, Massimiliano Copetti, Radmila Pavlovic, Denise Drago, Carla Fiorentini, Fulvia Terracciano, Francesca Bazzocchi, Giuseppe Canistro, Federica Pisati, Evaristo Maiello, Tiziana Pia Latiano, Francesco Perri, Valerio Pazienza
Journal: Gut Microbes (2024)

Pancreatic cancer has a dismal prognosis, as it is often diagnosed at stage IV of the disease and is characterized by metastatic spread. Gut microbiota and its metabolites have been suggested to influence the metastatic spread by modulating the host immune system or by promoting angiogenesis. To date, the gut microbial profiles of metastatic and non-metastatic patients need to be explored. Taking advantage of the 16S metagenomic sequencing and the PEnalized LOgistic Regression Analysis (PELORA) we identified clusters of bacteria with differential abundances between metastatic and non-metastatic patients. An overall increase in Gram-negative bacteria in metastatic patients compared to non-metastatic ones was identified using this method. Furthermore, to gain more insight into how gut microbes can predict metastases, a machine learning approach (iterative Random Forest) was performed. Iterative Random Forest analysis revealed which microorganisms were characterized by a different level of relative abundance between metastatic and non-metastatic patients and established a functional relationship between the relative abundance and the probability of having metastases. At the species level, the following bacteria were found to have the highest discriminatory power: Anaerostipes hadrus, Coprobacter secundus, Clostridium sp. 619, Roseburia inulinivorans, Porphyromonas and Odoribacter at the genus level, and Rhodospirillaceae, Clostridiaceae and Peptococcaceae at the family level. Finally, these data were intertwined with those from a metabolomics analysis on fecal samples of patients with or without metastasis to better understand the role of gut microbiota in the metastatic process. Artificial intelligence has been applied in different areas of the medical field. Translating its application in the field of gut microbiota analysis may help fully exploit the potential information contained in such a large amount of data aiming to open up new supportive areas of intervention in the management of cancer.
Human nasal epithelial cells express <scp>IL</scp>‐<scp>5Rα</scp> but not the co‐receptor <scp>CSF2RB</scp> and do not signal to <scp>IL</scp>‐5
Authors: Aaqib Sohail, Laura Cho, Jonathan Hacker, Regan W. Bergmark, Stella E. Lee, Alice Maxfield, Rachel E. Roditi, Daniel F. Dwyer, Kathleen M. Buchheit, Tanya M. Laidlaw
Journal: Allergy (2024)

The data that support the findings of this study are available from the corresponding author upon reasonable request. Data S1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
“Stop playing politics with my kid:” Thematic analysis of a trans-exclusionary sports legislation hearing in Texas
Authors: Kye Campbell-Fox, Devon Kimball, Jae A. Puckett, Terra Dunn, Sol Rabine
Journal: International Journal of Transgender Health (2024)

Background In recent years, legislation targeting transgender and gender diverse (TGD) people has proliferated in the United States, particularly legislation focused on TGD youth and on athletic inclusion. One such law, Texas House Bill 25 (HB25), focused on prohibiting TGD youth from participating in school sports in Texas.
Gut hormone stimulation as a therapeutic approach in oral peptide delivery
Authors: Ana Beloqui
Journal: Journal of Controlled Release (2024)

In this contribution to the Orations - New Horizons of the Journal of Controlled Release, I discuss the research that we have conducted on gut hormone stimulation as a therapeutic strategy in oral peptide delivery. One of the greatest challenges in oral drug delivery involves the development of new drug delivery systems that enable the absorption of therapeutic peptides into the systemic circulation at therapeutically relevant concentrations. This scenario is especially challenging in the treatment of chronic diseases (such as type 2 diabetes mellitus), wherein daily injections are often needed. However, for certain peptides, there may be an alternative in drug delivery to meet the need for increased peptide bioavailability; this is the case for gut hormone mimetics (including glucagon-like peptide (GLP)-1 or GLP-2). One plausible alternative for improved oral delivery of these peptides is the co-stimulation of the endogenous secretion of the hormone to reach therapeutic levels of the peptide. This oration will be focused on studies conducted on the stimulation of gut hormones secreted from enteroendocrine L cells in the treatment of gastrointestinal disorders, including a critical discussion of the limitations and future perspectives of implementing this approach in the clinical setting.
Tumor phagocytosis-driven STING activation invigorates antitumor immunity and reprograms the tumor micro-environment
Authors: Susam Lee, Kyeong Hee Hong, Heewon Park, JongHoon Ha, Seung Eon Lee, Dong Jin Park, Seong Dong Jeong, Seohyeon Kim, Dahae Kim, JiWon Ahn, Han-Woong Lee, Won-Gun Koh, Sang-Jun Ha, Yeu-Chun Kim
Journal: Journal of Controlled Release (2024)