tbuckley/cabot-search huggingface dataset:
Prognostic Value of Combined Assessments of Late Gadolinium Enhancement and Fluorodeoxyglucose Uptake in Cardiac Sarcoidosis
Authors: Sho Kazui, Sakae Takenaka, Toshiyuki Nagai, Satonori Tsuneta, Kenji Hirata, Yoshiya Kato, Hirokazu Komoriyama, Yuta Kobayashi, Akinori Takahashi, Kiwamu Kamiya, Taro Temma, Takuma Sato, Atsushi Tada, Yutaro Yasui, Michikazu Nakai, Takahiro Sato, Ichizo Tsujino, Kohsuke Kudo, Satoshi Konno, Toshihisa Anzai
Journal: JACC. Cardiovascular imaging (2024)
Cytoplasmic calcium influx mediated by plant MLKLs confers TNL-triggered immunity
Authors: Qiaochu Shen, Keiichi Hasegawa, Nicole Oelerich, Anna Prakken, Lea Weiler Tersch, Junli Wang, Frowin Reichhardt, Alexandra Tersch, Je Cuan Choo, Ton Timmers, Kay Hofmann, Jane E. Parker, Jijie Chai, Takaki Maekawa
Journal: Cell Host & Microbe (2024)

The plant homolog of vertebrate necroptosis inducer mixed-lineage kinase domain-like (MLKL) contributes to downstream steps in Toll-interleukin-1 receptor domain NLR (TNL)-receptor-triggered immunity. Here, we show that Arabidopsis MLKL1 (AtMLKL1) clusters into puncta at the plasma membrane upon TNL activation and that this sub-cellular reorganization is dependent on the TNL signal transducer, EDS1. We find that AtMLKLs confer TNL-triggered immunity in parallel with RPW8-type HeLo-domain-containing NLRs (RNLs) and that the AtMLKL N-terminal HeLo domain is indispensable for both immunity and clustering. We show that the AtMLKL HeLo domain mediates cytoplasmic Ca
Opposing diet, microbiome, and metabolite mechanisms regulate inflammatory bowel disease in a genetically susceptible host
Authors: Gabriel Vasconcelos Pereira, Marie Boudaud, Mathis Wolter, Celeste Alexander, Alessandro De Sciscio, Erica T. Grant, Bruno Caetano Trindade, Nicholas A. Pudlo, Shaleni Singh, Austin Campbell, Mengrou Shan, Li Zhang, Qinnan Yang, Stéphanie Willieme, Kwi Kim, Trisha Denike-Duval, Jaime Fuentes, André Bleich, Thomas M. Schmidt, Lucy Kennedy, Costas A. Lyssiotis, Grace Y. Chen, Kathryn A. Eaton, Mahesh S. Desai, Eric C. Martens
Journal: Cell Host & Microbe (2024)

Inflammatory bowel diseases (IBDs) are chronic conditions characterized by periods of spontaneous intestinal inflammation and are increasing in industrialized populations. Combined with host genetics, diet and gut bacteria are thought to contribute prominently to IBDs, but mechanisms are still emerging. In mice lacking the IBD-associated cytokine, interleukin-10, we show that a fiber-deprived gut microbiota promotes the deterioration of colonic mucus, leading to lethal colitis. Inflammation starts with the expansion of natural killer cells and altered immunoglobulin-A coating of some bacteria. Lethal colitis is then driven by Th1 immune responses to increased activities of mucin-degrading bacteria that cause inflammation first in regions with thinner mucus. A fiber-free exclusive enteral nutrition diet also induces mucus erosion but inhibits inflammation by simultaneously increasing an anti-inflammatory bacterial metabolite, isobutyrate. Our findings underscore the importance of focusing on microbial functions—not taxa—contributing to IBDs and that some diet-mediated functions can oppose those that promote disease.
A specific enterotype derived from gut microbiome of older individuals enables favorable responses to immune checkpoint blockade therapy
Authors: Xiaoqiang Zhu, Xiaowen Huang, Muni Hu, Rongrong Sun, Jiantao Li, Hai Wang, Xuefeng Pan, Yanru Ma, Lijun Ning, Tianying Tong, Yilu Zhou, Jinmei Ding, Ying Zhao, Baoqin Xuan, Jing-Yuan Fang, Jie Hong, Jason Wing Hon Wong, Youwei Zhang, Haoyan Chen
Journal: Cell Host & Microbe (2024)
Optical coherence tomography as a potential surrogate marker of dopaminergic modulation across the life span
Authors: Julia Elmers, Lorenza S. Colzato, Focke Ziemssen, Tjalf Ziemssen, Christian Beste
Journal: Ageing Research Reviews (2024)

The retina has been considered a "window to the brain" and shares similar innervation by the dopaminergic system with the cortex in terms of an unequal distribution of D1 and D2 receptors. Here, we provide a comprehensive overview that Optical Coherence Tomography (OCT), a non-invasive imaging technique, which provides an "in vivo" representation of the retina, shows promise to be used as a surrogate marker of dopaminergic neuromodulation in cognition. Overall, most evidence supports reduced retinal thickness in individuals with dopaminergic dysregulation (e.g., patients with Parkinson's Disease, non-demented older adults) and with poor cognitive functioning. By using the theoretical framework of metacontrol, we derive hypotheses that retinal thinning associated to decreased dopamine (DA) levels affecting D1 families, might lead to a decrease in the signal-to-noise ratio (SNR) affecting cognitive persistence (depending on D1-modulated DA activity) but not cognitive flexibility (depending on D2-modulated DA activity). We argue that the use of OCT parameters might not only be an insightful for cognitive neuroscience research, but also a potentially effective tool for individualized medicine with a focus on cognition. As our society progressively ages in the forthcoming years and decades, the preservation of cognitive abilities and promoting healthy aging will hold of crucial significance. OCT has the potential to function as a swift, non-invasive, and economical method for promptly recognizing individuals with a heightened vulnerability to cognitive deterioration throughout all stages of life.
Transcriptomic, epigenomic, and spatial metabolomic cell profiling redefines regional human kidney anatomy
Authors: Haikuo Li, Dian Li, Nicolas Ledru, Qiao Xuanyuan, Haojia Wu, Amish Asthana, Lori N. Byers, Stefan G. Tullius, Giuseppe Orlando, Sushrut S. Waikar, Benjamin D. Humphreys
Journal: Cell Metabolism (2024)

A large-scale multimodal atlas that includes major kidney regions is lacking. Here, we employed simultaneous high-throughput single-cell ATAC/RNA sequencing (SHARE-seq) and spatially resolved metabolomics to profile 54 human samples from distinct kidney anatomical regions. We generated transcriptomes of 446,267 cells and chromatin accessibility profiles of 401,875 cells and developed a package to analyze 408,218 spatially resolved metabolomes. We find that the same cell type, including thin limb, thick ascending limb loop of Henle and principal cells, display distinct transcriptomic, chromatin accessibility, and metabolomic signatures, depending on anatomic location. Surveying metabolism-associated gene profiles revealed non-overlapping metabolic signatures between nephron segments and dysregulated lipid metabolism in diseased proximal tubule (PT) cells. Integrating multimodal omics with clinical data identified PLEKHA1 as a disease marker, and its in vitro knockdown increased gene expression in PT differentiation, suggesting possible pathogenic roles. This study highlights previously underrepresented cellular heterogeneity underlying the human kidney anatomy.
Cytosolic pH is a direct nexus in linking environmental cues with insulin processing and secretion in pancreatic β cells
Authors: Yujiang Fang, Hexi Feng, Bowen Zhang, Shuwei Zhang, Yanjie Zhou, Pengcheng Hao, Zhongshu Zhou, Shanshan Zhou, Nan Li, Yi Hui, Lin Ma, Jie Xiong, Jinjin Wu, Ling Liu, Xiaoqing Zhang
Journal: Cell Metabolism (2024)
Behavioral Therapy for Functional Heartburn: Recommendation Statements
Authors: Livia Guadagnoli, Rena Yadlapati, John Pandolfino, Alyse Bedell, Anjali U. Pandit, Kerry B. Dunbar, Ronnie Fass, Richard Gevirtz, C. Prakash Gyawali, Stephen E. Lupe, Megan Petrik, Megan E. Riehl, Jessica Salwen-Deremer, Madison Simons, Kathryn N. Tomasino, Tiffany Taft
Journal: Clinical Gastroenterology and Hepatology (2024)
P-tau217 correlates with neurodegeneration in Alzheimer’s disease, and targeting p-tau217 with immunotherapy ameliorates murine tauopathy
Authors: Denghong Zhang, Wei Zhang, Chen Ming, Xuheng Gao, Huilong Yuan, Xiaojie Lin, Xinru Mao, Chunping Wang, Xiaoyi Guo, Ying Du, Lin Shao, Renzhi Yang, Zhihao Lin, Xilin Wu, Timothy Y. Huang, Zhanxiang Wang, Yun-wu Zhang, Huaxi Xu, Yingjun Zhao
Journal: Neuron (2024)
Intrathecal Gene Therapy for Giant Axonal Neuropathy
Authors: Diana X. Bharucha-Goebel, Joshua J. Todd, Dimah Saade, Gina Norato, Minal Jain, Tanya Lehky, Rachel M. Bailey, Jessica A. Chichester, Roberto Calcedo, Diane Armao, A. Reghan Foley, Payam Mohassel, Eshetu Tesfaye, Bradley P. Carlin, Beth Seremula, Melissa Waite, Wadih M. Zein, Laryssa A. Huryn, Thomas O. Crawford, Charlotte J. Sumner, Ahmet Hoke, John D. Heiss, Lawrence Charnas, Jody E. Hooper, Thomas W. Bouldin, Elizabeth M. Kang, Denis Rybin, Steven J. Gray, Carsten G. Bönnemann
Journal: New England Journal of Medicine (2024)

Giant axonal neuropathy is a rare, autosomal recessive, pediatric, polysymptomatic, neurodegenerative disorder caused by biallelic loss-of-function variants in
Alzheimer’s Disease — Managing Stages of Dementia
Authors: Nathaniel A. Chin, Debra Dinsmore, Tony Gonzales, Betsy Groves, Stephanie Houston, Dan Johnson, DeLois Johnson, Julia Napolitano, Allan Ropper, Stephen Salloway, Rob Sutherland, Lori Weiss, Karen Wheelock
Journal: New England Journal of Medicine (2024)
Case 9-2024: An 84-Year-Old Man with a Fall
Authors: Zaven Sargsyan, Sunita D. Srivastava, Virginia A. Triant, Brian B. Ghoshhajra
Journal: New England Journal of Medicine (2024)

An 84-year-old man was evaluated at the hospital for a fall and admitted for treatment of a presumed urinary tract infection. On hospital day 4, severe chest pain developed. A diagnosis was made.
Ribociclib plus Endocrine Therapy in Early Breast Cancer
Authors: Dennis Slamon, Oleg Lipatov, Zbigniew Nowecki, Nicholas McAndrew, Bozena Kukielka-Budny, Daniil Stroyakovskiy, Denise A. Yardley, Chiun-Sheng Huang, Peter A. Fasching, John Crown, Aditya Bardia, Stephen Chia, Seock-Ah Im, Manuel Ruiz-Borrego, Sherene Loi, Binghe Xu, Sara Hurvitz, Carlos Barrios, Michael Untch, Rebecca Moroose, Frances Visco, Karen Afenjar, Rodrigo Fresco, Irene Severin, Yan Ji, Farhat Ghaznawi, Zheng Li, Juan P. Zarate, Arunava Chakravartty, Tetiana Taran, Gabriel Hortobagyi
Journal: New England Journal of Medicine (2024)

Ribociclib has been shown to have a significant overall survival benefit in patients with hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer. Whether this benefit in advanced breast cancer extends to early breast cancer is unclear. Download a PDF of the Research Summary. In this international, open-label, randomized, phase 3 trial, we randomly assigned patients with HR-positive, HER2-negative early breast cancer in a 1:1 ratio to receive ribociclib (at a dose of 400 mg per day for 3 weeks, followed by 1 week off, for 3 years) plus a nonsteroidal aromatase inhibitor (NSAI; letrozole at a dose of 2.5 mg per day or anastrozole at a dose of 1 mg per day for ≥5 years) or an NSAI alone. Premenopausal women and men also received goserelin every 28 days. Eligible patients had anatomical stage II or III breast cancer. Here we report the results of a prespecified interim analysis of invasive disease–free survival, the primary end point; other efficacy and safety results are also reported. Invasive disease–free survival was evaluated with the use of the Kaplan–Meier method. The statistical comparison was made with the use of a stratified log-rank test, with a protocol-specified stopping boundary of a one-sided P-value threshold of 0.0128 for superior efficacy. As of the data-cutoff date for this prespecified interim analysis (January 11, 2023), a total of 426 patients had had invasive disease, recurrence, or death. A significant invasive disease–free survival benefit was seen with ribociclib plus an NSAI as compared with an NSAI alone. At 3 years, invasive disease–free survival was 90.4% with ribociclib plus an NSAI and 87.1% with an NSAI alone (hazard ratio for invasive disease, recurrence, or death, 0.75; 95% confidence interval, 0.62 to 0.91; P=0.003). Secondary end points — distant disease–free survival and recurrence-free survival — also favored ribociclib plus an NSAI. The 3-year regimen of ribociclib at a 400-mg starting dose plus an NSAI was not associated with any new safety signals. Ribociclib plus an NSAI significantly improved invasive disease–free survival among patients with HR-positive, HER2-negative stage II or III early breast cancer. (Funded by Novartis; NATALEE ClinicalTrials.gov number, NCT03701334.) QUICK TAKE VIDEO SUMMARYRibociclib in Early Breast Cancer 02:00
A subpopulation of luminal progenitors secretes pleiotrophin to promote angiogenesis and metastasis in inflammatory breast cancer
Authors: Mengmeng Zhang, Kaiwen Zhou, Zilin Wang, Ting Liu, Laura E. Stevens, Filipa Lynce, Wendy Y. Chen, Sui Peng, Yubin Xie, Duanyang Zhai, Qianjun Chen, Yawei Shi, Huijuan Shi, Zhongyu Yuan, Xiaoping Li, Juan Xu, Zhenhai Cai, Jianping Guo, Nan Shao, Ying Lin
Journal: Cancer Research (2024)

Inflammatory breast cancer (IBC) is a highly aggressive subtype of breast cancer characterized by rapidly arising diffuse erythema and edema. Genomic studies have not identified consistent alterations and mechanisms that differentiate IBC from non-IBC tumors, suggesting that the microenvironment could be a potential driver of IBC phenotypes. Here, using single-cell RNA sequencing, multiplex staining, and serum analysis in patients with IBC, we identified enrichment of a subgroup of luminal progenitor (LP) cells containing high expression of the neurotropic cytokine pleiotrophin (PTN) in IBC tumors. PTN secreted by the LP cells promoted angiogenesis by directly interacting with the NRP1 receptor on endothelial tip cells located in both IBC tumors and the affected skin. NRP1 activation in tip cells led to recruitment of immature perivascular cells in the affected skin of IBC, which are correlated with increased angiogenesis and IBC metastasis. Together, these findings reveal a role for cross-talk between LPs, endothelial tip cells, and immature perivascular cells via PTN-NRP1 axis in the pathogenesis of IBC, which could lead to improved strategies for treating IBC.
Risks of Fetal Exposure to Topiramate
Authors: Kimford J. Meador
Journal: New England Journal of Medicine (2024)

Antiseizure medications are commonly used in persons of childbearing potential for multiple indications (e.g., epilepsy, pain, and psychiatric disorders). All antiseizure medications are potential teratogens that could cause congenital malformations and cognitive or behavioral impairments.1 However, these effects vary markedly across antiseizure medications. For example, fetal exposure to valproate has been repeatedly associated with neuropsychological impairments, whereas many studies have shown no such association with fetal exposure to lamotrigine.2 A recent large, population-based study involving five Nordic countries showed an association between fetal exposure to topiramate and the risk of autism spectrum disorder.3 Among children born to mothers with epilepsy, . . .
Glucose Oxidase Energized Osmium with Dual‐Active Centers and Triple Enzyme Activities for Infected Diabetic Wound Management
Authors: Shaobin He, Mengting Lin, Qionghua Zheng, Bo Liang, Xinjie He, Yin Zhang, Qiuxia Xu, Haohua Deng, Kelong Fan, Wei Chen
Journal: Advanced Healthcare Materials (2024)

Diabetic wounds are susceptible to bacterial infections, largely linked to high blood glucose levels (hyperglycemia). To treat such wounds, enzymes like glucose oxidase (GOx) can be combined with nanozymes (nanomaterials mimic enzymes) to use glucose effectively for purposes. However, there is still room for improvement in these systems, particularly in terms of process simplification, enzyme activity regulation, and treatment effects. Herein, the approach utilizes GOx to directly facilitate the biomineralized growth of osmium (Os) nanozyme (GOx-OsNCs), leading to dual-active centers and remarkable triple enzyme activities. Initially, GOx-OsNCs use vicinal dual-active centers, enabling a self-cascaded mechanism that significantly enhances glucose sensing performance compared to step-by-step reactions, surpassing the capabilities of other metal sources such as gold and platinum. In addition, GOx-OsNCs are integrated into a glucose-sensing gel, enabling instantaneous visual feedback. In the treatment of infected diabetic wounds, GOx-OsNCs exhibit multifaceted benefits by lowering blood glucose levels and exhibiting antibacterial properties through the generation of hydroxyl free radicals, thereby expediting healing by fostering a favorable microenvironment. Furthermore, the catalase-like activity of GOx-OsNCs aids in reducing oxidative stress, inflammation, and hypoxia, culminating in improved healing outcomes. Overall, this synergistic enzyme-nanozyme blend is user-friendly and holds considerable promise for diverse applications.
Risk of Autism after Prenatal Topiramate, Valproate, or Lamotrigine Exposure
Authors: Sonia Hernández-Díaz, Loreen Straub, Brian T. Bateman, Yanmin Zhu, Helen Mogun, Katherine L. Wisner, Kathryn J. Gray, Barry Lester, Christopher J. McDougle, Elyse DiCesare, Page B. Pennell, Krista F. Huybrechts
Journal: New England Journal of Medicine (2024)

Maternal use of valproate during pregnancy has been associated with an increased risk of neurodevelopmental disorders in children. Although most studies of other antiseizure medications have not shown increased risks of these disorders, there are limited and conflicting data regarding the risk of autism spectrum disorder associated with maternal topiramate use. We identified a population-based cohort of pregnant women and their children within two health care utilization databases in the United States, with data from 2000 through 2020. Exposure to specific antiseizure medications was defined on the basis of prescription fills from gestational week 19 until delivery. Children who had been exposed to topiramate during the second half of pregnancy were compared with those unexposed to any antiseizure medication during pregnancy with respect to the risk of autism spectrum disorder. Valproate was used as a positive control, and lamotrigine was used as a negative control. The estimated cumulative incidence of autism spectrum disorder at 8 years of age was 1.9% for the full population of children who had not been exposed to antiseizure medication (4,199,796 children). With restriction to children born to mothers with epilepsy, the incidence was 4.2% with no exposure to antiseizure medication (8815 children), 6.2% with exposure to topiramate (1030 children), 10.5% with exposure to valproate (800 children), and 4.1% with exposure to lamotrigine (4205 children). Propensity score–adjusted hazard ratios in a comparison with no exposure to antiseizure medication were 0.96 (95% confidence interval [CI], 0.56 to 1.65) for exposure to topiramate, 2.67 (95% CI, 1.69 to 4.20) for exposure to valproate, and 1.00 (95% CI, 0.69 to 1.46) for exposure to lamotrigine. The incidence of autism spectrum disorder was higher among children prenatally exposed to the studied antiseizure medications than in the general population. However, after adjustment for indication and other confounders, the association was substantially attenuated for topiramate and lamotrigine, whereas an increased risk remained for valproate. (Funded by the National Institute of Mental Health.)
Anti–Interleukin-23 Autoantibodies in Adult-Onset Immunodeficiency
Authors: Aristine Cheng, Anuj Kashyap, Helene Salvator, Lindsey B. Rosen, Devon Colby, Fatemeh Ardeshir-Larijani, Patrick J. Loehrer, Li Ding, Saul O. Lugo Reyes, Sean Riminton, Madison Ballman, Joseph M. Rocco, Beatriz E. Marciano, Alexandra F. Freeman, Sarah K. Browne, Amy P. Hsu, Adrian Zelazny, Arun Rajan, Irini Sereti, Christa S. Zerbe, Michail S. Lionakis, Steven M. Holland
Journal: New England Journal of Medicine (2024)

Autoantibodies against interleukin-12 (anti-interleukin-12) are often identified in patients with thymoma, but opportunistic infections develop in only some of these patients. Interleukin-12 (with subunits p40 and p35) shares a common subunit with interleukin-23 (subunits p40 and p19). In a patient with disseminated
Effects of a Bioengineered Allogeneic Cellularized Construct (BACC) on Primary Human Macrophage Phenotype
Authors: Lindsay A. Steele, Beatriz Hernaez Estrada, Kara L. Spiller
Journal: Advanced Healthcare Materials (2024)

The mechanisms behind the pro-healing effects of multicellular, bioengineered allogeneic cellularized constructs (BACC) are not known. Macrophages are key regulators of every phase of the wound healing process and the primary cells that mediate the response to biomaterials. It is hypothesized that cells within the BACC modulate macrophage behavior, which may contribute to the mechanism by which BACC promotes healing. To probe the influence of cells within the BACC compared to effects of the underlying collagen substrate, primary human macrophages are cultured in direct or indirect contact with BACC or with the same collagen substrate used in the BACC manufacturing. Macrophage phenotype is characterized over time via multiplex gene expression, protein secretion, multidimensional flow cytometry, and functional assays with fibroblasts and endothelial cells. The BACC causes macrophages to exhibit a predominately reparative phenotype over time compared to relevant collagen substrate controls, with multiple subpopulations expressing both pro-inflammatory and reparative markers. Conditioned media from macrophage-BACC co-cultures causes distinct effects on fibroblast and endothelial cell proliferation, migration, and network formation. Given the critical role of the reparative macrophage phenotype in wound healing, these results suggest that modulation of macrophage phenotype may be a critical part of the mechanisms behind BACC's pro-healing effects.
The Diverse Evolutionary Histories of Domesticated Metaviral Capsid Genes in Mammals
Authors: William S Henriques, Janet M Young, Artem Nemudryi, Anna Nemudraia, Blake Wiedenheft, Harmit S Malik
Journal: Molecular Biology and Evolution (2024)

Selfish genetic elements comprise significant fractions of mammalian genomes. In rare instances, host genomes domesticate segments of these elements for function. Using a complete human genome assembly and 25 additional vertebrate genomes, we re-analyzed the evolutionary trajectories and functional potential of capsid (CA) genes domesticated from Metaviridae, a lineage of retrovirus-like retrotransposons. Our study expands on previous analyses to unearth several new insights about the evolutionary histories of these ancient genes. We find that at least five independent domestication events occurred from diverse Metaviridae, giving rise to three universally retained single-copy genes evolving under purifying selection and two gene families unique to placental mammals, with multiple members showing evidence of rapid evolution. In the SIRH/RTL family, we find diverse amino-terminal domains, widespread loss of protein-coding capacity in RTL10 despite its retention in several mammalian lineages, and differential utilization of an ancient programmed ribosomal frameshift in RTL3 between the domesticated CA and protease domains. Our analyses also reveal that most members of the PNMA family in mammalian genomes encode a conserved putative amino-terminal RNA-binding domain (RBD) both adjoining and independent from domesticated CA domains. Our analyses lead to a significant correction of previous annotations of the essential CCDC8 gene. We show that this putative RBD is also present in several extant Metaviridae, revealing a novel protein domain configuration in retrotransposons. Collectively, our study reveals the divergent outcomes of multiple domestication events from diverse Metaviridae in the common ancestor of placental mammals.