tbuckley/cabot-search huggingface dataset:
Tracer-Separator
Authors: Amirhossein Sanaat, Yiyi Hu, Cecilia Boccalini, Yazdan Salimi, Zahra Mansouri, Eliluane Pirazzo Andrade Teixeira, Gregory Mathoux, Valentina Garibotto, Habib Zaidi
Journal: Clinical Nuclear Medicine (2024)

Introduction Multiplexed PET imaging revolutionized clinical decision-making by simultaneously capturing various radiotracer data in a single scan, enhancing diagnostic accuracy and patient comfort. Through a transformer-based deep learning, this study underscores the potential of advanced imaging techniques to streamline diagnosis and improve patient outcomes. Patients and Methods The research cohort consisted of 120 patients spanning from cognitively unimpaired individuals to those with mild cognitive impairment, dementia, and other mental disorders. Patients underwent various imaging assessments, including 3D T1-weighted MRI, amyloid PET scans using either 18 F-florbetapir (FBP) or 18 F-flutemetamol (FMM), and 18 F-FDG PET. Summed images of FMM/FBP and FDG were used as proxy for simultaneous scanning of 2 different tracers. A SwinUNETR model, a convolution-free transformer architecture, was trained for image translation. The model was trained using mean square error loss function and 5-fold cross-validation. Visual evaluation involved assessing image similarity and amyloid status, comparing synthesized images with actual ones. Statistical analysis was conducted to determine the significance of differences. Results Visual inspection of synthesized images revealed remarkable similarity to reference images across various clinical statuses. The mean centiloid bias for dementia, mild cognitive impairment, and healthy control subjects and for FBP tracers is 15.70 ± 29.78, 0.35 ± 33.68, and 6.52 ± 25.19, respectively, whereas for FMM, it is −6.85 ± 25.02, 4.23 ± 23.78, and 5.71 ± 21.72, respectively. Clinical evaluation by 2 readers further confirmed the model's efficiency, with 97 FBP/FMM and 63 FDG synthesized images (from 120 subjects) found similar to ground truth diagnoses (rank 3), whereas 3 FBP/FMM and 15 FDG synthesized images were considered nonsimilar (rank 1). Promising sensitivity, specificity, and accuracy were achieved in amyloid status assessment based on synthesized images, with an average sensitivity of 95 ± 2.5, specificity of 72.5 ± 12.5, and accuracy of 87.5 ± 2.5. Error distribution analyses provided valuable insights into error levels across brain regions, with most falling between −0.1 and +0.2 SUV ratio. Correlation analyses demonstrated strong associations between actual and synthesized images, particularly for FMM images (FBP: Y = 0.72X + 20.95, R 2 = 0.54; FMM: Y = 0.65X + 22.77, R 2 = 0.77). Conclusions This study demonstrated the potential of a novel convolution-free transformer architecture, SwinUNETR, for synthesizing realistic FDG and FBP/FMM images from summation scans mimicking simultaneous dual-tracer imaging.
N6‐methyladenosine reader YTHDF3‐mediated zinc finger protein 41 inhibits hepatocellular carcinoma progression by transcriptional repression of Snail
Authors: Xinxin Li, Mengzhen Han, He Zhu, Hongwei Zhang, Yonglong Pan, Huifang Liang, Zhibin Liao, Bixiang Zhang, Xiaoping Chen
Journal: MedComm (2024)

Abstract Advanced metastasis of hepatocellular carcinoma (HCC) significantly contributes to high death rates among patients. The efficiency of targeted therapies and chemotherapeutic agents shows individual variability. Therefore, there is no effective treatment for advanced HCC. Zinc finger proteins (ZFPs) are known to be crucial in various tumors, especially on HCC. In our study, we verified that ZFP41 could suppress the progression and metastasis of HCC through in vitro and in vivo experiments. During the past years, N6‐methyladenine (m 6 A) regulation has also been increasingly reported in HCC. To investigate whether ZFP41 could be regulated via m 6 A methylation, our results showed that YTHDF3 bound to the mRNA of ZFP41 and degrade it. Subsequently, to further elucidate the function of ZFP41, we identified Snail, a well‐known oncogenic molecule, through RNA‐seq. As a canonical component in the epithelial‐to‐mesenchymal transition (EMT) pathway, Snail plays a pivotal role and is a critical marker for tumor invasion and metastasis. Our results showed ZFP41 could inhibit Snail and the EMT pathway through its transcriptional repression. In conclusion, our study revealed that ZFP41 is a potential prognostic element for patients with HCC, and targeting ZFP41 might be used for translational clinical applications as a promising therapeutic target.
Comprehensive single‐cell profiling of monocytes in HLA‐B27‐positive ankylosing spondylitis with acute anterior uveitis
Authors: Huan Li, Xueming Ju, Lixin Zhang, Jing Zhu, Jing Zhang, Jialing Xiao, Ting Wang, Weijia Wu, Liang Wang, Chengzi Gan, Xiangmei Li, Yutong Wei, Siyu Zhu, Yu Zhou, Bolin Deng, Ning Xiao, Bo Gong
Journal: MedComm (2024)

Abstract Acute anterior uveitis (AAU) is a common extra‐articular manifestation of ankylosing spondylitis (AS), particularly in patients positive for the human leucocyte antigen (HLA)‐B27 genetic marker. To explore the underlying mechanisms of HLA‐B27 + AS‐associated AAU, we employed single‐cell RNA sequencing to profile the transcriptomes of peripheral blood mononuclear cells in three HLA‐B27 + AS‐associated AAU patients and three healthy controls (HCs). We identified 11 distinct immune cell clusters, with a particular focus on monocytes, revealing six subsets, including three previously unidentified subsets, namely, GTPase immune‐associated proteins, Th17‐related, and lncRNA monocytes, with unique gene expression patterns. Significant differences in monocyte composition, activation states, and gene expression were observed between patients and HCs, particularly within HLA monocyte subpopulations. Notably, enhanced expression of X‐inactive specific transcript and myeloid cell nuclear differentiation antigen genes was validated across monocyte subclusters in patients. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis highlighted significant enrichment in antigen processing and presentation pathways, shedding light on the disease's molecular mechanisms. These findings provide novel insights into the molecular mechanisms of HLA‐B27 + AS‐associated AAU and may contribute to the development of targeted diagnostic and therapeutic strategies. Further clinical validation is essential.
Targeting immunosenescence for improved tumor immunotherapy
Authors: Zaoqu Liu, Lulu Zuo, Zhaokai Zhou, Shutong Liu, Yuhao Ba, Anning Zuo, Yuqing Ren, Chuhan Zhang, Yukang Chen, Hongxuan Ma, Yudi Xu, Peng Luo, Quan Cheng, Hui Xu, Yuyuan Zhang, Siyuan Weng, Xinwei Han
Journal: MedComm (2024)

Abstract Tumor immunotherapy has significantly transformed the field of oncology over the past decade. An optimal tumor immunotherapy would ideally elicit robust innate and adaptive immune responses within tumor immune microenvironment (TIME). Unfortunately, immune system experiences functional decline with chronological age, a process termed “immunosenescence,” which contributes to impaired immune responses against pathogens, suboptimal vaccination outcomes, and heightened vulnerability to various diseases, including cancer. In this context, we will elucidate hallmarks and molecular mechanisms underlying immunosenescence, detailing alterations in immunosenescence at molecular, cellular, organ, and disease levels. The role of immunosenescence in tumorigenesis and senescence‐related extracellular matrix (ECM) has also been addressed. Recognizing that immunosenescence is a dynamic process influenced by various factors, we will evaluate treatment strategies targeting hallmarks and molecular mechanisms, as well as methods for immune cell, organ restoration, and present emerging approaches in immunosenescence for tumor immunotherapy. The overarching goal of immunosenescence research is to prevent tumor development, recurrence, and metastasis, ultimately improving patient prognosis. Our review aims to reveal latest advancements and prospective directions in the field of immunosenescence research, offering a theoretical basis for development of practical anti‐immunosenescence and anti‐tumor strategies.
Reduced intestinal‐to‐diffuse conversion and immunosuppressive responses underlie superiority of neoadjuvant immunochemotherapy in gastric adenocarcinoma
Authors: Lei Wang, Linghong Wan, Xu Chen, Peng Gao, Yongying Hou, Linyu Wu, Wenkang Liu, Shuoran Tian, Mengyi Han, Shiyin Peng, Yuting Tan, Yuwei Pan, Yuanfeng Ren, Jinyang Li, Haihui Wen, Qin Liu, Mengsi Zhang, Tao Wang, Zhong‐Yi Qin, Junyu Xiang, Dongfeng Chen, Xianfeng Li, Shu‐Nan Wang, Chuan Chen, Mengxia Li, Fan Li, Zhenning Wang, Bin Wang
Journal: MedComm (2024)

Abstract Neoadjuvant immunochemotherapy (NAIC) achieves superior clinical benefits over neoadjuvant chemotherapy (NAC) in multiple types of human cancers, including gastric adenocarcinoma (GAC). However, it is poorly understood how the malignant epithelial cells and tumor immune microenvironment (TIME) might respond distinctly to NAIC and NAC that underlies therapeutic efficacy. Here treatment‐naive and paired tumor tissues from multiple centers were subjected to pathological, immunological, and transcriptomic analysis. NAIC demonstrated significantly increased rate of pathological complete response compared to NAC (pCR: 25% vs. 4%, p &lt; 0.05). Interestingly, pretreatment intestinal subtype of Lauren's classification was predictive of pathologic regression following NAIC, but not NAC. A substantial portion of cancers underwent intestinal‐to‐diffuse transition, which occurred less following NAIC and correlated with treatment failure. Moreover, NAIC prevented reprogramming to an immunosuppressive TIME with less active fibroblasts and exhausted CD8 + T cells, and increased numbers of mature tertiary lymphoid structures. Mechanistically, activation of the tumor necrosis factor alpha (TNFα)/nuclear factor‐kappa B (NF‐κB) signaling pathway was associated with response to NAIC. Together, NAIC is superior to NAC for locally advanced GAC, likely due to reduced intestinal‐to‐diffuse conversion and reprogramming to an immuno‐active TIME. Modulation of the histological conversion and immunosuppressive TIME could be translatable approaches to improve neoadjuvant therapeutic efficacy.
Machine learning‐based radiomics in neurodegenerative and cerebrovascular disease
Authors: Ming‐Ge Shi, Xin‐Meng Feng, Hao‐Yang Zhi, Lei Hou, Dong‐Fu Feng
Journal: MedComm (2024)

Abstract Cognitive impairments, which can be caused by neurodegenerative and cerebrovascular disease, represent a growing global health crisis with far‐reaching implications for individuals, families, healthcare systems, and economies worldwide. Notably, neurodegenerative‐induced cognitive impairment often presents a different pattern and severity compared to cerebrovascular‐induced cognitive impairment. With the development of computational technology, machine learning techniques have developed rapidly, which offers a powerful tool in radiomic analysis, allowing a more comprehensive model that can handle high‐dimensional, multivariate data compared to the traditional approach. Such models allow the prediction of the disease development, as well as accurately classify disease from overlapping symptoms, therefore facilitating clinical decision making. This review will focus on the application of machine learning‐based radiomics on cognitive impairment caused by neurogenerative and cerebrovascular disease. Within the neurodegenerative category, this review primarily focuses on Alzheimer's disease, while also covering other conditions such as Parkinson's disease, Lewy body dementia, and Huntington's disease. In the cerebrovascular category, we concentrate on poststroke cognitive impairment, including ischemic and hemorrhagic stroke, with additional attention given to small vessel disease and moyamoya disease. We also review the specific challenges and limitations when applying machine learning radiomics, and provide our suggestion to overcome those limitations towards the end, and discuss what could be done for future clinical use.
TRPV1 alleviates APOE4-dependent microglial antigen presentation and T cell infiltration in Alzheimer's disease
Authors: Jia Lu, Kexin Wu, Xudong Sha, Jiayuan Lin, Hongzhuan Chen, Zhihua Yu
Journal: Translational Neurodegeneration (2024)

Abstract Background Persistent innate and adaptive immune responses in the brain contribute to the progression of Alzheimer’s disease (AD). APOE4 , the most important genetic risk factor for sporadic AD, encodes apolipoprotein E4, which by itself is a potent modulator of immune response. However, little is known about the immune hub that governs the crosstalk between the nervous and the adaptive immune systems. Transient receptor potential vanilloid type 1 (TRPV1) channel is a ligand-gated, nonselective cation channel with Ca 2+ permeability, which has been proposed as a neuroprotective target in AD. Methods Using Ca 2+ -sensitive dyes, dynamic changes of Ca 2+ in microglia were measured, including exogenous Ca 2+ uptake and endoplasmic reticulum Ca 2+ release. The mRFP-GFP-tagged LC3 plasmid was expressed in microglia to characterize the role of TRPV1 in the autophagic flux. Transcriptomic analyses and flow cytometry were performed to investigate the effects of APOE4 on brain microglia and T cells from APOE -targeted replacement mice with microglia-specific TRPV1 gene deficiency. Results Both APOE4 microglia derived from induced pluripotent stem cells of AD patients and APOE4 -related tauopathy mouse model showed significantly increased cholesterol biosynthesis and accumulation compared to their APOE3 counterparts. Further, cholesterol dysregulation was associated with persistent activation of microglia and elevation of major histocompatibility complex II-dependent antigen presentation in microglia, subsequently accompanied by T cell infiltration. In addition, TRPV1-mediated transient Ca 2+ influx mitigated cholesterol biosynthesis in microglia by suppressing the transcriptional activation of sterol regulatory element-binding protein 2, promoted autophagic activity and reduced lysosomal cholesterol accumulation, which were sufficient to resolve excessive immune response and neurodegeneration in APOE4 -related tauopathy mouse model. Moreover, microglia-specific deficiency of TRPV1 gene accelerated glial inflammation, T cell response and associated neurodegeneration in an APOE4 -related tauopathy mouse model. Conclusions The findings provide new perspectives for the treatment of APOE4 -dependent neurodegeneration including AD.
Glut3 promotes cellular O-GlcNAcylation as a distinctive tumor-supportive feature in Treg cells
Authors: Amit Sharma, Garima Sharma, Zhen Gao, Ke Li, Mutong Li, Menglin Wu, Chan Johng Kim, Yingjia Chen, Anupam Gautam, Hong Bae Choi, Jin Kim, Jung-Myun Kwak, Sin Man Lam, Guanghou Shui, Sandip Paul, Yongqiang Feng, Keunsoo Kang, Sin-Hyeog Im, Dipayan Rudra
Journal: Cellular and Molecular Immunology (2024)
Transposable element diversity and activity patterns in neotropical salamanders
Authors: Louis Paul Decena-Segarra, Sean M Rovito
Journal: Molecular Biology and Evolution (2024)

Transposable elements (TEs) compose a substantial proportion of the largest eukaryotic genomes. TE diversity has been hypothesized to be negatively correlated with genome size, yet empirical demonstrations of such a relationship in a phylogenetic context are largely lacking. Furthermore, the most abundant type of TEs in genomes varies across groups, and it is not clear if there are patterns of TE activity consistent with genome size among different taxa with large genome sizes. We use low-coverage sequencing of 16 species of Neotropical salamanders, which vary approximately seven-fold in genome size, to estimate TE relative abundance and diversity for each species. We also compare divergence of copies of each TE superfamily to estimate patterns of TE activity in each species. We find a negative relationship between TE diversity and genome size, which is consistent with the hypothesis that either competition among TEs or reduced selection against ectopic recombination may result in lower diversity in the largest genomes. We also find divergent activity patterns in the largest vs. the smallest genomes, suggesting that the history of TE activity may explain differences in genome size. Our results suggest that both TE diversity and relative abundance may be predictable, at least within taxonomic groups.
Digital AVATAR therapy for distressing voices in psychosis: the phase 2/3 AVATAR2 trial
Authors: Philippa A Garety, Clementine J Edwards, Hassan Jafari, Richard Emsley, Mark Huckvale, Mar Rus-Calafell, Miriam Fornells-Ambrojo, Andrew Gumley, Gillian Haddock, Sandra Bucci, Hamish J McLeod, Jeffrey McDonnell, Moya Clancy, Michael Fitzsimmons, Hannah Ball, Alice Montague, Nikos Xanidis, Amy Hardy, Thomas K J Craig, Thomas Ward
Journal: Nature Medicine (2024)
Targeted sonodynamic therapy induces tumor cell quasi-immunogenic ferroptosis and macrophage immunostimulatory autophagy in glioblastoma
Authors: Meng-Fei Wang, Jie Guo, Shen-Jun Yuan, Ke Li, Quan Zhang, Hui-Mei Lei, Jia-Lin Wu, Li Zhao, Yong-Hong Xu, Xiao Chen
Journal: Biomaterials (2024)
Associations between Fine Particulate Matter Components, Their Sources, and Cognitive Outcomes in Children Ages 9–10 Years Old from the United States
Authors: Kirthana Sukumaran, Katherine L. Botternhorn, Joel Schwartz, Jim Gauderman, Carlos Cardenas-Iniguez, Rob McConnell, Daniel A. Hackman, Kiros Berhane, Hedyeh Ahmadi, Shermaine Abad, Rima Habre, Megan M. Herting
Journal: Environmental Health Perspectives (2024)

Emerging literature suggests that fine particulate matter [with aerodynamic diameter
SPRINTing to Conclusions
Authors: Gregory L. Hundemer, Manish M. Sood
Journal: Journal of the American Society of Nephrology (2024)

Division of Nephrology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; and Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada Correspondence: Dr. Manish M. Sood, email: [email protected] See related article, "The Legacy Effect of Intensive versus Standard BP Control on the Incidence of Needing Dialysis or Kidney Transplantation," on pages XXX–XXX.
Transcatheter Valve Replacement in Severe Tricuspid Regurgitation
Authors: Rebecca T Hahn, Raj Makkar, Vinod H Thourani, Moody Makar, Rahul P Sharma, Christiane Haeffele, Charles J Davidson, Akhil Narang, Brian O'Neill, James Lee, Pradeep Yadav, Firas Zahr, Scott Chadderdon, Mackram Eleid, Sorin Pislaru, Robert Smith, Molly Szerlip, Brian Whisenant, Nishant K Sekaran, Santiago Garcia, Terri Stewart-Dehner, Holger Thiele, Robert Kipperman, Konstantinos Koulogiannis, D Scott Lim, Dale Fowler, Samir Kapadia, Serge C Harb, Paul A Grayburn, Anna Sannino, Michael J Mack, Martin B Leon, Philipp Lurz, Susheel K Kodali
Journal: New England Journal of Medicine (2024)

BackgroundSevere tricuspid regurgitation is associated with disabling symptoms and an increased risk of death. Data regarding outcomes after percutaneous transcatheter tricuspid-valve replacement are needed.MethodsIn this international, multicenter trial, we randomly assigned 400 patients with severe symptomatic tricuspid regurgitation in a 2:1 ratio to undergo either transcatheter tricuspid-valve replacement and medical therapy (valve-replacement group) or medical therapy alone (control group). The hierarchical composite primary outcome was death from any cause, implantation of a right ventricular assist device or heart transplantation, postindex tricuspid-valve intervention, hospitalization for heart failure, an improvement of at least 10 points in the score on the Kansas City Cardiomyopathy Questionnaire overall summary (KCCQ-OS), an improvement of at least one New York Heart Association (NYHA) functional class, and an improvement of at least 30 m on the 6-minute walk distance. A win ratio was calculated for the primary outcome by comparing all possible patient pairs, starting with the first event in the hierarchy.ResultsA total of 267 patients were assigned to the valve-replacement group and 133 to the control group. At 1 year, the win ratio favoring valve replacement was 2.02 (95% confidence interval [CI], 1.56 to 2.62; P<0.001). In comparisons of patient pairs, those in the valve-replacement group had more wins than the control group with respect to death from any cause (14.8% vs. 12.5%), postindex tricuspid-valve intervention (3.2% vs. 0.6%), and improvement in the KCCQ-OS score (23.1% vs. 6.0%), NYHA class (10.2% vs. 0.8%), and 6-minute walk distance (1.1% vs. 0.9%). The valve-replacement group had fewer wins than the control group with respect to the annualized rate of hospitalization for heart failure (9.7% vs. 10.0%). Severe bleeding occurred in 15.4% of the valve-replacement group and in 5.3% of the control group (P=0.003); new permanent pacemakers were implanted in 17.4% and 2.3%, respectively (P<0.001).ConclusionsFor patients with severe tricuspid regurgitation, transcatheter tricuspid-valve replacement was superior to medical therapy alone for the primary composite outcome, driven primarily by improvements in symptoms and quality of life. (Funded by Edwards Lifesciences; TRISCEND II ClinicalTrials.gov number, NCT04482062.)
Liver Transplant Using Normothermic Machine Perfusion in Patients With High-Acuity Illness
Authors: Samer S. Ebaid, Francesca A. Kimelman, Koki Maeda, Christopher S. Chandler, Vatche G. Agopian, Douglas G. Farmer, Fady M. Kaldas
Journal: JAMA Surgery (2024)

This case-control study compares outcomes of normothermic machine perfusion vs static cold storage used in liver transplant for complex patients.
The Ongoing Dilemma of Timing Noncardiac Surgery After NSTEMI
Authors: Emily Smith, Laura Young, Faisal G. Bakaeen
Journal: JAMA Surgery (2024)

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