tbuckley/cabot-search huggingface dataset:
Generation of antigen-specific mature T cells from RAG1−/−RAG2−/−B2M−/− stem cells by engineering their microenvironment
Authors: Patrick C Chang, Xuegang Yuan, Alexandre Zampieri, Chloe Towns, Sang Pil Yoo, Claire Engstrom, Steven Tsai, Christopher R. Robles, Yuhua Zhu, Shawn Lopez, Amelie Montel-Hagen, Christopher S. Seet, Gay M. Crooks
Journal: Nature Biomedical Engineering (2023)

Abstract Pluripotent stem cells (PSCs) are a promising source of allogeneic T cells for off-the-shelf immunotherapies. However, the process of differentiating genetically engineered PSCs to generate mature T cells requires that the same molecular elements that are crucial for the selection of these cells be removed to prevent alloreactivity. Here we show that antigen-restricted mature T cells can be generated in vitro from PSCs edited via CRISPR to lack endogenous T cell receptors (TCRs) and class I major histocompatibility complexes. Specifically, we used T cell precursors from RAG1 −/− RAG2 − /− B2M − /− human PSCs expressing a single TCR, and a murine stromal cell line providing the cognate human major histocompatibility complex molecule and other critical signals for T cell maturation. Possibly owing to the absence of TCR mispairing, the generated T cells showed substantially better tumour control in mice than T cells with an intact endogenous TCR. Introducing the T cell selection components into the stromal microenvironment of the PSCs overcomes inherent biological challenges associated with the development of T cell immunotherapies from allogeneic PSCs.
Multi-ancestry study of the genetics of problematic alcohol use in over 1 million individuals
Authors: Hang Zhou, Rachel L. Kember, Joseph D. Deak, Heng Xu, Sylvanus Toikumo, Kai Yuan, Penelope A. Lind, Leila Farajzadeh, Lu Wang, Alexander S. Hatoum, Jessica Johnson, Hyunjoon Lee, Travis T. Mallard, Jiayi Xu, Keira J. A. Johnston, Emma C. Johnson, Trine Tollerup Nielsen, Marco Galimberti, Cecilia Dao, Daniel F. Levey, Cassie Overstreet, Enda M. Byrne, Nathan A. Gillespie, Scott Gordon, Ian B. Hickie, John B. Whitfield, Ke Xu, Hongyu Zhao, Laura M. Huckins, Lea K. Davis, Sandra Sanchez-Roige, Pamela A. F. Madden, Andrew C. Heath, Sarah E. Medland, Nicholas G. Martin, Tian Ge, Jordan W. Smoller, David M. Hougaard, Anders D. Børglum, Ditte Demontis, John H. Krystal, J. Michael Gaziano, Howard J. Edenberg, Arpana Agrawal, Hongyu Zhao, Amy C. Justice, Murray B. Stein, Henry R. Kranzler, Joel Gelernter
Journal: Nature Medicine (2023)

Abstract Problematic alcohol use (PAU), a trait that combines alcohol use disorder and alcohol-related problems assessed with a questionnaire, is a leading cause of death and morbidity worldwide. Here we conducted a large cross-ancestry meta-analysis of PAU in 1,079,947 individuals (European, N = 903,147; African, N = 122,571; Latin American, N = 38,962; East Asian, N = 13,551; and South Asian, N = 1,716 ancestries). We observed a high degree of cross-ancestral similarity in the genetic architecture of PAU and identified 110 independent risk variants in within- and cross-ancestry analyses. Cross-ancestry fine mapping improved the identification of likely causal variants. Prioritizing genes through gene expression and chromatin interaction in brain tissues identified multiple genes associated with PAU. We identified existing medications for potential pharmacological studies by a computational drug repurposing analysis. Cross-ancestry polygenic risk scores showed better performance of association in independent samples than single-ancestry polygenic risk scores. Genetic correlations between PAU and other traits were observed in multiple ancestries, with other substance use traits having the highest correlations. This study advances our knowledge of the genetic etiology of PAU, and these findings may bring possible clinical applicability of genetics insights—together with neuroscience, biology and data science—closer.
Predictors of early morbidity and mortality in newly diagnosed multiple myeloma: data from five randomized, controlled, phase III trials in 3700 patients
Authors: Elias K. Mai, Thomas Hielscher, Uta Bertsch, Hans J. Salwender, Sonja Zweegman, Marc S. Raab, Markus Munder, Lucia Pantani, Katia Mancuso, Peter Brossart, Meral Beksac, Igor W. Blau, Jan Dürig, Britta Besemer, Roland Fenk, Peter Reimer, Bronno van der Holt, Mathias Hänel, Ivana von Metzler, Ullrich Graeven, Carsten Müller-Tidow, Mario Boccadoro, Christof Scheid, Meletios A. Dimopoulos, Jens Hillengass, Katja C. Weisel, Michele Cavo, Pieter Sonneveld, Hartmut Goldschmidt
Journal: Leukemia (2023)

Abstract Early morbidity and mortality affect patient outcomes in multiple myeloma. Thus, we dissected the incidence and causes of morbidity/mortality during induction therapy (IT) for newly diagnosed multiple myeloma (NDMM), and developed/validated a predictive risk score. We evaluated 3700 transplant-eligible NDMM patients treated in 2005–2020 with novel agent-based triplet/quadruplet IT. Primary endpoints were severe infections, death, or a combination of both. Patients were divided in a training ( n = 1333) and three validation cohorts ( n = 2367). During IT, 11.8%, 1.8%, and 12.5% of patients in the training cohort experienced severe infections, death, or both, respectively. Four major, baseline risk factors for severe infection/death were identified: low platelet count (&lt;150/nL), ISS III, higher WHO performance status (&gt;1), and age (&gt;60 years). A risk score (1 risk factor=1 point) stratified patients in low (39.5%; 0 points), intermediate (41.9%; 1 point), and high (18.6%; ≥2 points) risk. The risk for severe infection/death increased from 7.7% vs. 11.5% vs. 23.3% in the low- vs. intermediate- vs. high-risk groups ( p &lt; 0.001). The risk score was independently validated in three trials incorporating quadruplet IT with an anti-CD38 antibody. Our analyses established a robust and easy-to-use score to identify NDMM patients at risk of severe infection/death, covering the latest quadruplet induction therapies. Trial registrations: HOVON-65/GMMG-HD4: EudraCT No. 2004-000944-26. GMMG-MM5: EudraCT No. 2010-019173-16. GMMG-HD6: NCT02495922. EMN02/HOVON-95: NCT01208766. GMMG-HD7: NCT03617731.
Oleic acid availability impacts thymocyte preprogramming and subsequent peripheral Treg cell differentiation
Authors: Liangyu Lin, Mingyuan Hu, Qing Li, Liming Du, Li Lin, Yueqing Xue, Fanjun Zheng, Fei Wang, Keli Liu, Yu Wang, Jiayin Ye, Xu Jiang, Xuefeng Wang, Jiaqi Wang, Jingjie Zhai, Benming Liu, Hongzhen Xie, Yanqin You, Jinyong Wang, Xiangyin Kong, Dechun Feng, Douglas R. Green, Yufang Shi, Ying Wang
Journal: Nature Immunology (2023)
GCLiPP: global crosslinking and protein purification method for constructing high-resolution occupancy maps for RNA binding proteins
Authors: Wandi S. Zhu, Adam J. Litterman, Harshaan S. Sekhon, Robin Kageyama, Maya M. Arce, Kimberly E. Taylor, Wenxue Zhao, Lindsey A. Criswell, Noah Zaitlen, David J. Erle, K. Mark Ansel
Journal: Genome biology (2023)

Abstract GCLiPP is a global RNA interactome capture method that detects RNA-binding protein (RBP) occupancy transcriptome-wide. GCLiPP maps RBP-occupied sites at a higher resolution than phase separation-based techniques. GCLiPP sequence tags correspond with known RBP binding sites and are enriched for sites detected by RBP-specific crosslinking immunoprecipitation (CLIP) for abundant cytosolic RBPs. Comparison of human Jurkat T cells and mouse primary T cells uncovers shared peaks of GCLiPP signal across homologous regions of human and mouse 3′ UTRs, including a conserved mRNA-destabilizing cis-regulatory element. GCLiPP signal overlapping with immune-related SNPs uncovers stabilizing cis-regulatory regions in CD5, STAT6, and IKZF1.
Development of osteonecrosis and improved survival in B-ALL: results of Children’s Oncology Group Trial AALL0232
Authors: Leonard A. Mattano, Meenakshi Devidas, Mignon L. Loh, Elizabeth A. Raetz, Zhiguo Chen, Naomi J. Winick, Stephen P. Hunger, William L. Carroll, Eric C. Larsen
Journal: Leukemia (2023)
Effect of Dapagliflozin Versus Placebo on Symptoms and 6-Minute Walk Distance in Patients With Heart Failure: The DETERMINE Randomized Clinical Trials
Authors: John J.V. McMurray, Kieran F. Docherty, Rudolf A. de Boer, Ann Hammarstedt, Dalane W. Kitzman, Mikhail N. Kosiborod, Anna Maria Langkilde, Barry Reicher, Michele Senni, Sanjiv J. Shah, Ulrica Wilderäng, Subodh Verma, Scott D. Solomon
Journal: Circulation (2023)

Sodium-glucose cotransporter 2 inhibitors reduce the risk of worsening heart failure (HF) and cardiovascular death in patients with HF irrespective of left ventricular ejection fraction. It is important to determine whether therapies for HF improve symptoms and functional capacity.
Resistance Exercise Training in Individuals With and Without Cardiovascular Disease: 2023 Update: A Scientific Statement From the American Heart Association
Authors: Amanda E. Paluch, William R. Boyer, Barry A. Franklin, Deepika Laddu, Felipe Lobelo, Duck-chul Lee, Mary M. McDermott, Damon L. Swift, Allison R. Webel, Abbi Lane
Journal: Circulation (2023)

Resistance training not only can improve or maintain muscle mass and strength, but also has favorable physiological and clinical effects on cardiovascular disease and risk factors. This scientific statement is an update of the previous (2007) American Heart Association scientific statement regarding resistance training and cardiovascular disease. Since 2007, accumulating evidence suggests resistance training is a safe and effective approach for improving cardiovascular health in adults with and without cardiovascular disease. This scientific statement summarizes the benefits of resistance training alone or in combination with aerobic training for improving traditional and nontraditional cardiovascular disease risk factors. We also address the utility of resistance training for promoting cardiovascular health in varied healthy and clinical populations. Because less than one-third of US adults report participating in the recommended 2 days per week of resistance training activities, this scientific statement provides practical strategies for the promotion and prescription of resistance training.
Continuous positive airway pressure for prevention of cardiovascular events and mortality: why evidence is evolving
Authors: Jean-Louis Pépin, Winfried Randerath
Journal: European Respiratory Journal (2023)

<h3>Tweetable abstract</h3> <b>Obstructive sleep apnoea is a risk factor for cardiovascular morbidity and mortality. There is a need for innovative research strategies evaluating the positive prognostic effects of CPAP. Hypoxic burden may guide individualised therapeutic approaches.</b>https://bit.ly/3MPuHq2
Cast no shadow: assessing the disease-modifying effects of elexacaftor/tezacaftor/ivacaftor
Authors: Peter J. Barry, Pierre-Régis Burgel
Journal: European Respiratory Journal (2023)

<h3>Tweetable abstract</h3> <b>Elexacaftor/tezacaftor/ivacaftor therapy shows promising results in terms of long-term lung function trajectories in people with cystic fibrosis, but these findings will require confirmation in a larger, unselected population</b>https://bit.ly/47yyoZ4
Photodynamic O<sub>2</sub> Economizer Encapsulated with DNAzyme for Enhancing Mitochondrial Gene‐Photodynamic Therapy
Authors: Kaipeng Zhong, Zefan Zhang, Wenyuan Cheng, Guangyao Liu, Xuan Zhang, Jing Zhang, Shihao Sun, Baodui Wang
Journal: Advanced Healthcare Materials (2023)

Emerging research suggests that mitochondrial DNA is a potential target for cancer treatment. However, achieving precise delivery of deoxyribozymes (DNAzymes) and combining photodynamic therapy (PDT) and DNAzyme-based gene silencing together for enhancing mitochondrial gene-photodynamic synergistic therapy remains challenging. Accordingly, herein, intelligent supramolecular nanomicelles are constructed by encapsulating a DNAzyme into a photodynamic O
Local Spinal Cord Injury Treatment Using a Dental Pulp Stem Cell Encapsulated H<sub>2</sub>S Releasing Multifunctional Injectable Hydrogel
Authors: Abdullkhaleg Ali Albashari, Yan He, Yu Luo, Xingxiang Duan, Jihea Ali, Mingchang Li, Dehao Fu, Yangfan Xiang, Youjian Peng, Song Li, Lihua Luo, Xingjie Zan, Tushar Kumeria, Qingsong Ye
Journal: Advanced Healthcare Materials (2023)

Spinal cord injury (SCI) commonly induces nerve damage and nerve cell degeneration. In this work, a novel dental pulp stem cells (DPSCs) encapsulated thermoresponsive injectable hydrogel with sustained hydrogen sulfide (H
A Review of Advanced Abdominal Wall Hernia Patch Materials
Authors: Kaiwen Liang, Cuicui Ding, Jingyi Li, Xiao Yao, Jingjing Yu, Hui Wu, Lihui Chen, Min Zhang
Journal: Advanced Healthcare Materials (2023)

Tension-free abdominal wall hernia patch materials (AWHPMs) play an important role in the repair of abdominal wall defects (AWDs), which have a recurrence rate of <1%. Nevertheless, there are still significant challenges in the development of tailored, biomimetic, and extracellular matrix (ECM)-like AWHPMs that satisfy the clinical demands of abdominal wall repair (AWR) while effectively handling post-operative complications associated with abdominal hernias, such as intra-abdominal visceral adhesion and abnormal healing. This extensive review presents a comprehensive guide to the high-end fabrication and the precise selection of these advanced AWHPMs. The review begins by briefly introducing the structures, sources, and properties of AWHPMs, and critically evaluates the advantages and disadvantages of different types of AWHPMs for AWR applications. The review subsequently summarizes and elaborates upon state-of-the-art AWHPM fabrication methods and their key characteristics (e.g., mechanical, physicochemical, and biological properties in vitro/vivo). This review uses compelling examples to demonstrate that advanced AWHPMs with multiple functionalities (e.g., anti-deformation, anti-inflammation, anti-adhesion, pro-healing properties, etc.) can meet the fundamental clinical demands required to successfully repair AWDs. In particular, there have been several developments in the enhancement of biomimetic AWHPMs with multiple properties, and additional breakthroughs are expected in the near future.
British Thoracic Society Clinical Statement on chronic cough in adults
Authors: Sean M Parker, Jaclyn Ann Smith, Surinder S Birring, Sarah Chamberlain-Mitchell, Kevin Gruffydd-Jones, Jemma Haines, Sarah Hennessey, Lorcan P McGarvey, Paul Marsden, Matthew James Martin, Alyn Morice, James O'Hara, Mike Thomas
Journal: Thorax (2023)

### Terminology, epidemiology and impact ### Causes of CC ### Clinical assessment ### Treatable traits in cough #### Smoking #### ACEI treatment #### Airway disease: productive cough #### Eosinophilic airway disease
CD74/SLC34A2-ROS1 Fusion Variants Involving the Transmembrane Region Predict Poor Response to Crizotinib in NSCLC Independent of TP53 Mutations
Authors: Weihua Li, Kailun Fei, Lei Guo, Yulan Wang, Chang Shu, Jie Wang, Jianming Ying
Journal: Journal of Thoracic Oncology (2023)

J o u r n a l P r e -p r o o f of TP53 mutations (P<0.001 and P=0.002, respectively).Conclusions: Long CD74/SLC34A2-ROS1 fusions, which retain transmembrane regions in ROS1 and fusion partners, are associated with poor response to crizotinib independent of TP53 mutations.
Nedosiran: First Approval
Authors: Yahiya Y. Syed
Journal: Drugs (2023)

Nedosiran (RIVFLOZA™), a once-monthly subcutaneous small interfering RNA (siRNA) therapy, is being developed by Dicerna Pharmaceuticals, a Novo Nordisk company, for the treatment of primary hyperoxaluria (PH). It reduces oxalate overproduction by inhibiting the expression of the hepatic lactate dehydrogenase (LDH) enzyme. Nedosiran received its first approval on 29 September 2023 in the USA to lower urinary oxalate levels in children aged ≥ 9 years and adults with PH type 1 (PH1) and relatively preserved kidney function [e.g. estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2]. This article summarizes the milestones in the development of nedosiran leading to this first approval for PH1.
A liquid biopsy signature of circulating extracellular vesicles-derived RNAs predicts response to first line chemotherapy in patients with metastatic colorectal cancer
Authors: Ya’nan Yang, Jieyun Zhang, Wen Zhang, Yixuan Wang, Yujia Zhai, Yan Li, Wenhua Li, Jinjia Chang, Xiaoying Zhao, Mingzhu Huang, Qirong Geng, Yue Yang, Zhe Gong, Nuoya Yu, Wei Shen, Qian Li, Shenglin Huang, Weijian Guo
Journal: Molecular Cancer (2023)

Abstract Background Colorectal cancer (CRC) is one of the most threatening tumors in the world, and chemotherapy remains dominant in the treatment of metastatic CRC (mCRC) patients. The purpose of this study was to develop a biomarker panel to predict the response of the first line chemotherapy in mCRC patients. Methods Totally 190 mCRC patients treated with FOLFOX or XEOLX chemotherapy in 3 different institutions were included. We extracted the plasma extracellular vesicle (EV) RNA, performed RNA sequencing, constructed a model and generated a signature through shrinking the number of variables by the random forest algorithm and the least absolute shrinkage and selection operator (LASSO) algorithm in the training cohort ( n = 80). We validated it in an internal validation cohort ( n = 62) and a prospective external validation cohort ( n = 48). Results We established a signature consisted of 22 EV RNAs which could identify responders, and the area under the receiver operating characteristic curve (AUC) values was 0.986, 0.821, and 0.816 in the training, internal validation, and external validation cohort respectively. The signature could also identify the progression-free survival (PFS) and overall survival (OS). Besides, we constructed a 7-gene signature which could predict tumor response to first-line oxaliplatin-containing chemotherapy and simultaneously resistance to second-line irinotecan-containing chemotherapy. Conclusions The study was first to develop a signature of EV-derived RNAs to predict the response of the first line chemotherapy in mCRC with high accuracy using a non-invasive approach, indicating that the signature could help to select the optimal regimen for mCRC patients.
The BCL-2 inhibitor APG-2575 resets tumor-associated macrophages toward the M1 phenotype, promoting a favorable response to anti-PD-1 therapy via NLRP3 activation
Authors: Fan Luo, Han Li, Wenjuan Ma, Jiaxin Cao, Qun Chen, Feiteng Lu, Miaozhen Qiu, Penghui Zhou, Zengfei Xia, Kangmei Zeng, Jianhua Zhan, Ting Zhou, Qiuyun Luo, Wentao Pan, Lin Zhang, Chaozhuo Lin, Yan Huang, Li Zhang, Dajun Yang, Hongyun Zhao
Journal: Cellular and Molecular Immunology (2023)

Abstract The main challenges in the use of immune checkpoint inhibitors (ICIs) are ascribed to the immunosuppressive tumor microenvironment and the lack of sufficient infiltration of activated CD8+ T cells. Transforming the tumor microenvironment (TME) from “cold” to “hot” and thus more likely to potentiate the effects of ICIs is a promising strategy for cancer treatment. We found that the selective BCL-2 inhibitor APG-2575 can enhance the antitumor efficacy of anti-PD-1 therapy in syngeneic and humanized CD34+ mouse models. Using single-cell RNA sequencing, we found that APG-2575 polarized M2-like immunosuppressive macrophages toward the M1-like immunostimulatory phenotype with increased CCL5 and CXCL10 secretion, restoring T-cell function and promoting a favorable immunotherapy response. Mechanistically, we demonstrated that APG-2575 directly binds to NF-κB p65 to activate NLRP3 signaling, thereby mediating macrophage repolarization and the activation of proinflammatory caspases and subsequently increasing CCL5 and CXCL10 chemokine production. As a result, APG-2575-induced macrophage repolarization could remodel the tumor immune microenvironment, thus improving tumor immunosuppression and further enhancing antitumor T-cell immunity. Multiplex immunohistochemistry confirmed that patients with better immunotherapeutic efficacy had higher CD86, p-NF-κB p65 and NLRP3 levels, accompanied by lower CD206 expression on macrophages. Collectively, these data provide evidence that further study on APG-2575 in combination with immunotherapy for tumor treatment is required.
Efficacy of fecal microbiota transplantation in patients with Parkinson’s disease: clinical trial results from a randomized, placebo-controlled design
Authors: Yi Cheng, Guohua Tan, Qihui Zhu, Chun Wang, Guangcong Ruan, Senhong Ying, Jinlong Qie, Xiaofei Hu, Zhifeng Xiao, Fenghua Xu, Lu Chen, Minjia Chen, Yang Pei, Hao Zhang, Yuting Tian, Dongfeng Chen, Xingyin Liu, Heqing Huang, Yanling Wei
Journal: Gut Microbes (2023)

The occurrence and development of Parkinson's disease (PD) have been demonstrated to be related to gut dysbiosis, however, the impact of fecal microbiota transplantation (FMT) on microbiota engraftment in PD patients is uncertain. We performed a randomized, placebo-controlled trial at the Department of Neurology, Army Medical University Southwest Hospital in China (ChiCTR1900021405) from February 2019 to December 2019. Fifty-six participants with mild to moderate PD (Hoehn-Yahr stage 1–3) were randomly assigned to the FMT and placebo group, 27 patients in the FMT group and 27 in the placebo group completed the whole trial. During the follow-up, no severe adverse effect was observed, and patients with FMT treatment showed significant improvement in PD-related autonomic symptoms compared with the placebo group at the end of this trial (MDS-UPDRS total score, group×time effect, B = -6.56 [−12.98, −0.13], P < 0.05). Additionally, FMT improved gastrointestinal disorders and a marked increase in the complexity of the microecological system in patients. This study demonstrated that FMT through oral administration is clinically feasible and has the potential to improve the effectiveness of current medications in the clinical symptoms of PD patients.
Modulating the polarization phenotype of microglia – A valuable strategy for central nervous system diseases
Authors: Yu Long, Xiao-qiu Li, Jie Deng, Qiao-bo Ye, Dan Li, Yin Ma, Yuan-yuan Wu, Yue Hu, Xiao-fang He, Jing Wen, Ai Shi, Shuang Yu, Lin Shen, Zhen Ye, Chuan Zheng, Nan Li
Journal: Ageing Research Reviews (2023)
Feasibility of decoding visual information from EEG
Authors: Holly Wilson, Xi Chen, Mohammad Golbabaee, Michael J. Proulx, Eamonn O’Neill
Journal: Brain-Computer Interfaces (2023)

Decoding visual information, such as visual imagery and perception, from EEG data can be used to improve understanding of the neural representation of visual information and to provide commands for BCI systems. The appeal of EEG as a neuroimaging tool lies in its high temporal resolution, cost-effectiveness, and portability. Nevertheless, the feasibility of using EEG for visual information decoding remains a subject of ongoing inquiry. In this review, we explore the neural correlates of this visual information, specifically focusing on visual features such as colour, shapes, texture, and also naturalistic whole objects. We begin to examine which visual features can be effectively measured using EEG, taking into account its inherent characteristics, such as its measurement depth, limited spatial resolution, and high temporal resolution. Using a systematic approach, the review provides an in-depth analysis of the current state-of-the-art in EEG-based decoding of visual features for BCI purposes. Finally, we address some potential methodological improvements that can be made to the experimental design in EEG visual information decoding studies, such as palette cleansing, augmentation to bolster dataset size, and fusion of neuroimaging techniques.