tbuckley/cabot-search huggingface dataset:
Integrating spatial and single-cell transcriptomics to characterize the molecular and cellular architecture of the ischemic mouse brain
Authors: Bing Han, Shunheng Zhou, Yuan Zhang, Sina Chen, Wen Xi, Chenchen Liu, Xu Zhou, Mengqin Yuan, Xiaoyu Yu, Lu Li, Yu Wang, Hui Ren, Jian Xie, Bin Li, Minzi Ju, You Zhou, Ziqi Liu, Zhongli Xiong, Ling Shen, Yuan Zhang, Ying Bai, Jun Chen, Wei Jiang, Honghong Yao
Journal: Science Translational Medicine (2024)

Neuroinflammation is acknowledged as a pivotal pathological event after cerebral ischemia. However, there is limited knowledge of the molecular and spatial characteristics of nonneuronal cells, as well as of the interactions between cell types in the ischemic brain. Here, we used spatial transcriptomics to study the ischemic hemisphere in mice after stroke and sequenced the transcriptomes of 19,777 spots, allowing us to both visualize the transcriptional landscape within the tissue and identify gene expression profiles linked to specific histologic entities. Cell types identified by single-cell RNA sequencing confirmed and enriched the spatial annotation of ischemia-associated gene expression in the peri-infarct area of the ischemic hemisphere. Analysis of ligand-receptor interactions in cell communication revealed galectin-9 to cell-surface glycoprotein CD44 (LGALS9-CD44) as a critical signaling pathway after ischemic injury and identified microglia and macrophages as the main source of galectins after stroke. Extracellular vesicle–mediated Lgals9 delivery improved the long-term functional recovery in photothrombotic stroke mice. Knockdown of Cd44 partially reversed these therapeutic effects, inhibiting oligodendrocyte differentiation and remyelination. In summary, our study provides a detailed molecular and cellular characterization of the peri-infact area in a murine stroke model and revealed Lgals9 as potential treatment target that warrants further investigation.
Phospholipid-inspired alkoxylation induces crystallization and cellular uptake of luminescent COF nanocarriers
Authors: Wei Zhang, Shuo Xiang, Yuxin Han, Haiyan Wang, Yuxian Deng, Panpan Bian, Yoshio Bando, Dmitri Golberg, Qunhong Weng
Journal: Biomaterials (2024)
CD23 <sup>+</sup> IgG1 <sup>+</sup> memory B cells are poised to switch to pathogenic IgE production in food allergy
Authors: Miyo Ota, Kenneth B. Hoehn, Weslley Fernandes-Braga, Takayuki Ota, Carlos J. Aranda, Sara Friedman, Mariana G. C. Miranda-Waldetario, Jamie Redes, Maria Suprun, Galina Grishina, Hugh A. Sampson, Alefiyah Malbari, Steven H. Kleinstein, Scott H. Sicherer, Maria A. Curotto de Lafaille
Journal: Science Translational Medicine (2024)

Food allergy is caused by allergen-specific immunoglobulin E (IgE) antibodies, but little is known about the B cell memory of persistent IgE responses. Here, we describe, in human pediatric peanut allergy, a population of CD23 + IgG1 + memory B cells arising in type 2 immune responses that contain high-affinity peanut-specific clones and generate IgE-producing cells upon activation. The frequency of CD23 + IgG1 + memory B cells correlated with circulating concentrations of IgE in children with peanut allergy. A corresponding population of “type 2–marked” IgG1 + memory B cells was identified in single-cell RNA sequencing experiments. These cells differentially expressed interleukin-4 (IL-4)– and IL-13–regulated genes, such as FCER2 / CD23 + , IL4R , and germline IGHE , and carried highly mutated B cell receptors (BCRs). In children with high concentrations of serum peanut-specific IgE, high-affinity B cells that bind the main peanut allergen Ara h 2 mapped to the population of “type 2–marked” IgG1 + memory B cells and included clones with convergent BCRs across different individuals. Our findings indicate that CD23 + IgG1 + memory B cells transcribing germline IGHE are a unique memory population containing precursors of high-affinity pathogenic IgE-producing cells that are likely to be involved in the long-term persistence of peanut allergy.
Association Analysis Provides Insights into Plant Mitonuclear Interactions
Authors: Qun Lian, Shuai Li, Shenglong Kan, Xuezhu Liao, Sanwen Huang, Daniel B Sloan, Zhiqiang Wu
Journal: Molecular Biology and Evolution (2024)

Abstract Cytonuclear interaction refers to the complex and ongoing process of coevolution between nuclear and organelle genomes, which are responsible for cellular respiration, photosynthesis, lipid metabolism, etc. and play a significant role in adaptation and speciation. There have been a large number of studies to detect signatures of cytonuclear interactions. However, identification of the specific nuclear and organelle genetic polymorphisms that are involved in these interactions within a species remains relatively rare. The recent surge in whole genome sequencing has provided us an opportunity to explore cytonuclear interaction from a population perspective. In this study, we analyzed a total of 3,439 genomes from 7 species to identify signals of cytonuclear interactions by association (linkage disequilibrium) analysis of variants in both the mitochondrial and nuclear genomes across flowering plants. We also investigated examples of nuclear loci identified based on these association signals using subcellular localization assays, gene editing, and transcriptome sequencing. Our study provides a novel perspective on the investigation of cytonuclear coevolution, thereby enriching our understanding of plant fitness and offspring sterility.
Unveiling inflammatory and prehypertrophic cell populations as key contributors to knee cartilage degeneration in osteoarthritis using multi-omics data integration
Authors: Yue Fan, Xuzhao Bian, Xiaogao Meng, Lei Li, Laiyi Fu, Yanan Zhang, Long Wang, Yan Zhang, Dalong Gao, Xiong Guo, Mikko Juhani Lammi, Guangdun Peng, Shiquan Sun
Journal: Annals of the Rheumatic Diseases (2024)

Objectives Single-cell and spatial transcriptomics analysis of human knee articular cartilage tissue to present a comprehensive transcriptome landscape and osteoarthritis (OA)-critical cell populations. Methods Single-cell RNA sequencing and spatially resolved transcriptomic technology have been applied to characterise the cellular heterogeneity of human knee articular cartilage which were collected from 8 OA donors, and 3 non-OA control donors, and a total of 19 samples. The novel chondrocyte population and marker genes of interest were validated by immunohistochemistry staining, quantitative real-time PCR, etc. The OA-critical cell populations were validated through integrative analyses of publicly available bulk RNA sequencing data and large-scale genome-wide association studies. Results We identified 33 cell population-specific marker genes that define 11 chondrocyte populations, including 9 known populations and 2 new populations, that is, pre-inflammatory chondrocyte population (preInfC) and inflammatory chondrocyte population (InfC). The novel findings that make this an important addition to the literature include: (1) the novel InfC activates the mediator MIF-CD74; (2) the prehypertrophic chondrocyte (preHTC) and hypertrophic chondrocyte (HTC) are potentially OA-critical cell populations; (3) most OA-associated differentially expressed genes reside in the articular surface and superficial zone; (4) the prefibrocartilage chondrocyte (preFC) population is a major contributor to the stratification of patients with OA, resulting in both an inflammatory-related subtype and a non-inflammatory-related subtype. Conclusions Our results highlight InfC, preHTC, preFC and HTC as potential cell populations to target for therapy. Also, we conclude that profiling of those cell populations in patients might be used to stratify patient populations for defining cohorts for clinical trials and precision medicine.
Systemically administered low-affinity HER2 CAR T cells mediate antitumor efficacy without toxicity
Authors: Tamer Basel Shabaneh, Andrew R Stevens, Sylvia M Stull, Kristen R Shimp, Brandon W Seaton, Ekram A Gad, Carla A Jaeger-Ruckstuhl, Sylvain Simon, Amanda L Koehne, Jason P Price, James M Olson, Benjamin G Hoffstrom, David Jellyman, Stanley R Riddell
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background The paucity of tumor-specific targets for chimeric antigen receptor (CAR) T-cell therapy of solid tumors necessitates careful preclinical evaluation of the therapeutic window for candidate antigens. Human epidermal growth factor receptor 2 (HER2) is an attractive candidate for CAR T-cell therapy in humans but has the potential for eliciting on-target off-tumor toxicity. We developed an immunocompetent tumor model of CAR T-cell therapy targeting murine HER2 (mHER2) and examined the effect of CAR affinity, T-cell dose, and lymphodepletion on safety and efficacy. Methods Antibodies specific for mHER2 were generated, screened for affinity and specificity, tested for immunohistochemical staining of HER2 on normal tissues, and used for HER2-targeted CAR design. CAR candidates were evaluated for T-cell surface expression and the ability to induce T-cell proliferation, cytokine production, and cytotoxicity when transduced T cells were co-cultured with mHER2+ tumor cells in vitro. Safety and efficacy of various HER2 CARs was evaluated in two tumor models and normal non-tumor-bearing mice. Results Mice express HER2 in the same epithelial tissues as humans, rendering these tissues vulnerable to recognition by systemically administered HER2 CAR T cells. CAR T cells designed with single-chain variable fragment (scFvs) that have high-affinity for HER2 infiltrated and caused toxicity to normal HER2-positive tissues but exhibited poor infiltration into tumors and antitumor activity. In contrast, CAR T cells designed with an scFv with low-affinity for HER2 infiltrated HER2-positive tumors and controlled tumor growth without toxicity. Toxicity mediated by high-affinity CAR T cells was independent of tumor burden and correlated with proliferation of CAR T cells post infusion. Conclusions Our findings illustrate the disadvantage of high-affinity CARs for targets such as HER2 that are expressed on normal tissues. The use of low-affinity HER2 CARs can safely regress tumors identifying a potential path for therapy of solid tumors that exhibit high levels of HER2.
Time to Treatment With Intravenous Thrombolysis Before Thrombectomy and Functional Outcomes in Acute Ischemic Stroke
Authors: Johannes Kaesmacher, Fabiano Cavalcante, Manon Kappelhof, Kilian M. Treurniet, Leon Rinkel, Jianmin Liu, Bernard Yan, Wenjie Zi, Kazumi Kimura, Omer F. Eker, Yongwei Zhang, Eike I. Piechowiak, Wim van Zwam, Sheng Liu, Daniel Strbian, Maarten Uyttenboogaart, Tomas Dobrocky, Zhongrong Miao, Kentaro Suzuki, Lei Zhang, Robert van Oostenbrugge, Thomas R. Meinel, Changwei Guo, David Seiffge, Congguo Yin, Lukas Bütikofer, Hester Lingsma, Daan Nieboer, Pengfei Yang, Peter Mitchell, Charles Majoie, Urs Fischer, Yvo Roos, Jan Gralla, Raul Nogueira, Qingwu Yang, Yuji Matsumaru, Steven Bush, Fengli Li, Jiacheng Huang, Jiaxing Song, Bo Hong, Wenhuo Chen, Ya Peng, Hongxing Han, Liyong Zhang, Shouchun Wang, Qi Fang, Chenghua Xu, Yongxin Zhang, Zifu Li, Pengfei Xing, Hongjian Shen, Ping Zhang, Xiaoxi Zhang, Stephen Davis, Huy-Thang Nguyen, Geoffrey Donnan, Xiaochuan Huo, Guangxian Nan, Andrew Bivard, Henry Ma, Vu Dang Luu, Bruce Campbell, Bart J Emmer, Jonathan M Coutinho, Natalie E LeCouffe, Diederik W J Dippel, Aad van der Lugt, Vincent Costalat, Geert Lycklama, Jeannette Hofmeijer, Anouk van Norden, Toshiaki Otsuka, Masataka Takeuchi, Masafumi Morimoto, Ryuzaburo Kanazawa, Yohei Takayama, Yuki Kamiya, Keigo Shigeta, Seiji Okubo, Mikito Hayakawa, Christophe Cognard, Simon Jung, Marnat Gaultier, Igor Sibon, Romain Bourcier, Solene de Gaalon, Chrysanthi Papagiannaki, Margaux Lefebvre, David S Liebeskind
Journal: JAMA (2024)

The benefit of intravenous thrombolysis (IVT) for acute ischemic stroke declines with longer time from symptom onset, but it is not known whether a similar time dependency exists for IVT followed by thrombectomy.
Understanding Mechanisms of Response to CAR T-cell Therapy through Single-Cell Sequencing: Insights and Challenges
Authors: Nicholas J. Haradhvala, Marcela V. Maus
Journal: Blood Cancer Discovery (2024)

Summary: Single-cell RNA sequencing has emerged as a powerful technique to understand the molecular features of chimeric antigen receptor (CAR) T cells that associate with clinical outcomes. Here we discuss the common themes that have emerged from across single-cell studies of CAR T-cell therapy, and summarize the challenges in interpreting this complex data type.
Basophils are important for development of allergic skin inflammation
Authors: Juan-Manuel Leyva-Castillo, Daniela Vega-Mendoza, Maria Strakosha, Liwen Deng, Samantha Choi, Kensuke Miyake, Hajime Karasuyama, Isaac M. Chiu, Wanda Phipatanakul, Raif S. Geha
Journal: Journal of Allergy and Clinical Immunology (2024)
The Alopecia Areata Severity and Morbidity Index (ASAMI) Study
Authors: Anthony Moussa, Michaela Bennett, Dmitri Wall, Nekma Meah, Katherine York, Laita Bokhari, Leila Asfour, Huw Rees, Leonardo Spagnol Abraham, Daniel Asz-Sigall, Fitnat Buket Basmanav, Wilma Bergfeld, Regina C. Betz, Bevin Bhoyrul, Ulrike Blume-Peytavi, Valerie Callender, Vijaya Chitreddy, Andrea Combalia, George Cotsarelis, Brittany Craiglow, Rachita Dhurat, Jeff Donovan, Andrei Doroshkevich, Samantha Eisman, Paul Farrant, Juan Ferrando, Aida Gadzhigoroeva, Jack Green, Ramon Grimalt, Matthew Harries, Maria Hordinsky, Alan Irvine, Victoria Jolliffe, Spartak Kaiumov, Brett King, Joyce Lee, Won-Soo Lee, Jane Li, Nino Lortkipanidze, Amy McMichael, Natasha Atanaskova Mesinkovska, Andrew Messenger, Paradi Mirmirani, Elise Olsen, Seth J. Orlow, Yuliya Ovcharenko, Bianca Maria Piraccini, Rodrigo Pirmez, Adriana Rakowska, Pascal Reygagne, Lidia Rudnicka, David Saceda Corralo, Maryanne Senna, Jerry Shapiro, Pooja Sharma, Tatiana Siliuk, Michela Starace, Poonkiat Suchonwanit, Anita Takwale, Antonella Tosti, Sergio Vañó-Galván, Willem I. Visser, Annika Vogt, Martin Wade, Leona Yip, Cheng Zhou, Rodney Sinclair
Journal: JAMA Dermatology (2024)

Current measures of alopecia areata (AA) severity, such as the Severity of Alopecia Tool score, do not adequately capture overall disease impact.
Commercial Blood Test May Identify Alzheimer Disease Brain Pathology
Authors: Emily Harris
Journal: JAMA (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
65 000 Rape-Related Pregnancies Took Place in US States With Abortion Bans
Authors: Emily Harris
Journal: JAMA (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Trends in Firearm Injury Prevention Research Funding, Clinical Trials, and Publications in the US, 1985-2022
Authors: John C. Lin, Christopher Chang, Madison S. McCarthy, Abe Baker-Butler, Guangyu Tong, Megan L. Ranney
Journal: JAMA Surgery (2024)

This cross-sectional study examines federal funding, registered clinical trials, and publications to quantify trends in firearm injury prevention research in the US from 1985 to 2022.
The Reliability of Traumatic and Adverse Experiences
Authors: Carl F. Weems
Journal: JAMA Psychiatry (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Self-Reported Walking Limitations Linked With Higher Risk of Fractures
Authors: Emily Harris
Journal: JAMA (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Traditional Atlantic Diet and Its Effect on Health and the Environment
Authors: Cristina Cambeses-Franco, Francisco Gude, Alfonso J. Benítez-Estévez, Sara González-García, Rosaura Leis, Juan Sánchez-Castro, María Teresa Moreira, Gumersindo Feijoo, Mar Calvo-Malvar
Journal: JAMA Network Open (2024)

Importance The universal call to action for healthier and more sustainable dietary choices is the framework of the United Nations’s Sustainable Development Goals. The Atlantic diet, originating from the northwest of the Iberian Peninsula, represents an example of a traditional diet that aligns with these principles. Objective To explore a 6-month intervention based on the Atlantic diet’s effects on metabolic and environmental health, assessing metabolic syndrome (MetS) incidence and the carbon footprint. Design, Setting, and Participants The Galician Atlantic Diet study was a 6-month randomized clinical trial designed to assess the effects of this regional traditional diet on families’ eating habits. The study was conducted from March 3, 2014, to May 29, 2015, at a local primary health care center in the rural town of A Estrada in northwestern Spain and involved a multisectoral collaboration. Families were randomly selected from National Health System records and randomized 1:1 to an intervention or control group. This secondary analysis of the trial findings was performed between March 24, 2021, and November 7, 2023. Interventions Over 6 months, families in the intervention group received educational sessions, cooking classes, written supporting material, and foods characteristic of the Atlantic diet, whereas those randomized to the control group continued with their habitual lifestyle. Main Outcomes and Measures The main outcomes were MetS incidence, defined per National Cholesterol Education Program Adult Treatment Panel III guidelines, and carbon footprint emissions as an environmental metric using life cycle assessment with daily dietary intake as the functional unit. Results Initially, 250 families were randomized (574 participants; mean [SD] age, 46.8 [15.7] years; 231 males [40.2%] and 343 females [59.8%]). The intervention group included 126 families (287 participants) and the control group, 124 families (287 participants). Ultimately, 231 families completed the trial. The intervention significantly reduced the risk of incident cases of MetS (rate ratio, 0.32; 95% CI, 0.13-0.79) and had fewer MetS components (proportional odds ratio, 0.58; 95% CI, 0.42-0.82) compared with the control condition. The intervention group did not have a significantly reduced environmental impact in terms of carbon footprint emissions compared with the control group (−0.17 [95% CI, −0.46 to 0.12] kg CO 2 equivalents/person/d). Conclusions and Relevance These findings provide important evidence that a family-focused dietary intervention based on a traditional diet can reduce the risk of incident MetS. Further research is needed to understand the underlying mechanisms and determine the generalizability to other populations, taking into account regional cultural and dietary variations. Trial Registration ClinicalTrials.gov Identifier: NCT02391701