tbuckley/cabot-search huggingface dataset:
Diffusion models for out-of-distribution detection in digital pathology
Authors: Jasper Linmans, Gabriel Raya, Jeroen van der Laak, Geert Litjens
Journal: Medical Image Analysis (2024)

The ability to detect anomalies, i.e. anything not seen during training or out-of-distribution (OOD), in medical imaging applications is essential for successfully deploying machine learning systems. Filtering out OOD data using unsupervised learning is especially promising because it does not require costly annotations. A new class of models called AnoDDPMs, based on denoising diffusion probabilistic models (DDPMs), has recently achieved significant progress in unsupervised OOD detection. This work provides a benchmark for unsupervised OOD detection methods in digital pathology. By leveraging fast sampling techniques, we apply AnoDDPM on a large enough scale for whole-slide image analysis on the complete test set of the Camelyon16 challenge. Based on ROC analysis, we show that AnoDDPMs can detect OOD data with an AUC of up to 94.13 and 86.93 on two patch-level OOD detection tasks, outperforming the other unsupervised methods. We observe that AnoDDPMs alter the semantic properties of inputs, replacing anomalous data with more benign-looking tissue. Furthermore, we highlight the flexibility of AnoDDPM towards different information bottlenecks by evaluating reconstruction errors for inputs with different signal-to-noise ratios. While there is still a significant performance gap with fully supervised learning, AnoDDPMs show considerable promise in the field of OOD detection in digital pathology.
BCG immunization induces CX3CR1hi effector memory T cells to provide cross-protection via IFN-γ-mediated trained immunity
Authors: Kim A. Tran, Erwan Pernet, Mina Sadeghi, Jeffrey Downey, Julia Chronopoulos, Elizabeth Lapshina, Oscar Tsai, Eva Kaufmann, Jun Ding, Maziar Divangahi
Journal: Nature Immunology (2024)
A collaborative realist review of remote measurement technologies for depression in young people
Authors: Annabel E. L. Walsh, Georgia Naughton, Thomas Sharpe, Zuzanna Zajkowska, Mantas Malys, Alastair van Heerden, Valeria Mondelli
Journal: Nature Human Behaviour (2024)

Abstract Digital mental health is becoming increasingly common. This includes use of smartphones and wearables to collect data in real time during day-to-day life (remote measurement technologies, RMT). Such data could capture changes relevant to depression for use in objective screening, symptom management and relapse prevention. This approach may be particularly accessible to young people of today as the smartphone generation. However, there is limited research on how such a complex intervention would work in the real world. We conducted a collaborative realist review of RMT for depression in young people. Here we describe how, why, for whom and in what contexts RMT appear to work or not work for depression in young people and make recommendations for future research and practice. Ethical, data protection and methodological issues need to be resolved and standardized; without this, RMT may be currently best used for self-monitoring and feedback to the healthcare professional where possible, to increase emotional self-awareness, enhance the therapeutic relationship and monitor the effectiveness of other interventions.
Publisher Correction: Rational design of a ‘two-in-one’ immunogen DAM drives potent immune response against mpox virus
Authors: Han Wang, Peng Yin, Tingting Zheng, Lanju Qin, Shihua Li, Pu Han, Xiao Qu, Jun Wen, Haoyi Ding, Jiahao Wu, Tianxiang Kong, Zhengrong Gao, Songtao Hu, Xin Zhao, Xiangyu Cao, Min Fang, Jianxun Qi, Jianzhong Jeff Xi, Kai Duan, Xiaoming Yang, Zhuobing Zhang, Qihui Wang, Wenjie Tan, George Fu Gao
Journal: Nature Immunology (2024)
Epigenetic Regulation of Cardiomyocyte Maturation by Arginine Methyltransferase CARM1
Authors: Tiffany A. Garbutt, Zhenhua Wang, Haofei Wang, Hong Ma, Hongmei Ruan, Yanhan Dong, Yifang Xie, Lianmei Tan, Ranan Phookan, Joy A. Stouffer, Vasanth Vedantham, Yuchen Yang, Li Qian, Jiandong Liu
Journal: Circulation (2024)

BACKGROUND: During the neonatal stage, the cardiomyocyte undergoes a constellation of molecular, cytoarchitectural, and functional changes known collectively as cardiomyocyte maturation to increase myocardial contractility and cardiac output. Despite the importance of cardiomyocyte maturation, the molecular mechanisms governing this critical process remain largely unexplored. METHODS: We leveraged an in vivo mosaic knockout system to characterize the role of Carm1 , the founding member of protein arginine methyltransferase, in cardiomyocyte maturation. Using a battery of assays, including immunohistochemistry, immuno-electron microscopy imaging, and action potential recording, we assessed the effect of loss of Carm1 function on cardiomyocyte cell growth, myofibril expansion, T-tubule formation, and electrophysiological maturation. Genome-wide transcriptome profiling, H3R17me2a chromatin immunoprecipitation followed by sequencing, and assay for transposase-accessible chromatin with high-throughput sequencing were used to investigate the mechanisms by which CARM1 (coactivator-associated arginine methyltransferase 1) regulates cardiomyocyte maturation. Finally, we interrogated the human syntenic region to the H3R17me2a chromatin immunoprecipitation followed by sequencing peaks for single-nucleotide polymorphisms associated with human heart diseases. RESULTS: We report that mosaic ablation of Carm1 disrupts multiple aspects of cardiomyocyte maturation cell autonomously, leading to reduced cardiomyocyte size and sarcomere thickness, severe loss and disorganization of T tubules, and compromised electrophysiological maturation. Genomics study demonstrates that CARM1 directly activates genes that underlie cardiomyocyte cytoarchitectural and electrophysiological maturation. Moreover, our study reveals significant enrichment of human heart disease–associated single-nucleotide polymorphisms in the human genomic region syntenic to the H3R17me2a chromatin immunoprecipitation followed by sequencing peaks. CONCLUSIONS: This study establishes a critical and multifaceted role for CARM1 in regulating cardiomyocyte maturation and demonstrates that deregulation of CARM1-dependent cardiomyocyte maturation gene expression may contribute to human heart diseases.
Metal‐Organic Framework‐Based Nanomedicines for Ferroptotic Cancer Therapy
Authors: Yue Song, Xinran Xu, Zheng Wang, Yanjun Zhao
Journal: Advanced Healthcare Materials (2024)

Abstract As an iron‐dependent, non‐apoptosis, regulated cell death (RCD) modality, ferroptosis has gained growing attention for cancer therapy. With the development of nanomaterials in the biomedical field, ferroptotic cancer nanomedicine is extensively investigated. Amongst various nanomaterials, metal‐organic frameworks (MOFs) are hybridized porous materials consisting of metal ions or clusters bridged by organic linkers. The superior properties of MOFs, such as high porosity and cargo loading, ease of surface modification, and good biocompatibility, make them appealing in inducing or sensitizing ferroptotic cell death. There are remarkable achievements in the field of MOF‐based ferroptosis cancer therapy. However, this topic is not reviewed. This review will introduce the fundamentals of MOF and ferroptosis machinery, summarize the recent progress of MOF‐based ferroptotic anticancer drug delivery, discuss the benefits and problems of MOFs as vehicles and sensitizers for cancer ferroptosis, and provide the perspective on future research direction on this promising field.
Wireless facial biosensing system for monitoring facial palsy with flexible microneedle electrode arrays
Authors: Wenjianlong Zhou, Zhongyan Wang, Qin Xu, Xiangxiang Liu, Junshi Li, Huaiqiang Yu, Hui Qiao, Lirui Yang, Liangpeng Chen, Yuan Zhang, Zhe Huang, Yuxing Pang, Zhitong Zhang, Jiayan Zhang, Xiudong Guan, Shunchang Ma, Yingjie Ren, Xiaoyi Shi, Linhao Yuan, Deling Li, Dong Huang, Zhihong Li, Wang Jia
Journal: npj Digital Medicine (2024)

Abstract Facial palsy (FP) profoundly influences interpersonal communication and emotional expression, necessitating precise diagnostic and monitoring tools for optimal care. However, current electromyography (EMG) systems are limited by their bulky nature, complex setups, and dependence on skilled technicians. Here we report an innovative biosensing approach that utilizes a PEDOT:PSS-modified flexible microneedle electrode array (P-FMNEA) to overcome the limitations of existing EMG devices. Supple system-level mechanics ensure excellent conformality to the facial curvilinear regions, enabling the detection of targeted muscular ensemble movements for facial paralysis assessment. Moreover, our apparatus adeptly captures each electrical impulse in response to real-time direct nerve stimulation during neurosurgical procedures. The wireless conveyance of EMG signals to medical facilities via a server augments access to patient follow-up evaluation data, fostering prompt treatment suggestions and enabling the access of multiple facial EMG datasets during typical 6-month follow-ups. Furthermore, the device’s soft mechanics alleviate issues of spatial intricacy, diminish pain, and minimize soft tissue hematomas associated with traditional needle electrode positioning. This groundbreaking biosensing strategy has the potential to transform FP management by providing an efficient, user-friendly, and less invasive alternative to the prevailing EMG devices. This pioneering technology enables more informed decision-making in FP-management and therapeutic intervention.
Effect of sodium-glucose cotransporter-2 inhibitors on continuous glucose monitoring metrics, as adjunctive to insulin in adults with type 1 diabetes mellitus: a meta-analysis of randomized controlled trials
Authors: Djordje S. Popovic, Paschalis Karakasis, Theocharis Koufakis, Nikolaos Fragakis, Nikolaos Papanas, Milena Mitrovic, Evanthia Gouveri, Dimitrios Patoulias
Journal: Metabolism (2024)
Fractures in Patients With Acute Calcium Pyrophosphate Crystal Arthritis Versus Matched Comparators in a Large Cohort Study
Authors: Sara K. Tedeschi, Keigo Hayashi, Ann Rosenthal, Muneet Gill, Javier Marrugo, Sho Fukui, Ellen Gravallese, Daniel H. Solomon
Journal: Arthritis & Rheumatology (2024)

Objective Calcium pyrophosphate deposition (CPPD) disease was associated with osteopenia in two cross‐sectional studies. We compared fracture risks in patients with acute calcium pyrophosphate (CPP) crystal arthritis versus matched comparators. Methods We performed a longitudinal cohort study using electronic health record data from a single large academic health system, with data from 1991 to 2023. Patients with one or more episodes of acute CPP crystal arthritis were matched to comparators on the index date (first documentation of “pseudogout” or synovial fluid CPP crystals or matched encounter) and first encounter in the health system. The primary outcome was first fracture at the humerus, wrist, hip, or pelvis. We excluded patients with fracture before the index date. Covariates included demographics, body mass index, smoking, comorbidities, health care use, glucocorticoids, and osteoporosis treatments. We estimated incidence rates and adjusted hazard ratios for fracture. Sensitivity analyses excluded patients prescribed glucocorticoids, patients prescribed osteoporosis treatments, or patients with rheumatoid arthritis and additionally adjusted for chronic kidney disease. Results We identified 1,148 patients with acute CPP crystal arthritis matched to 3,730 comparators, with a mean age of 73 years. Glucocorticoids and osteoporosis treatments were more frequent in the acute CPP crystal arthritis cohort. Fracture incidence rates were twice as high in the acute CPP crystal arthritis cohort (11.7 per 1,000 person‐years) versus comparators (5.5 per 1,000 person‐years). After multivariable adjustment, fracture relative risk was twice as high in the acute CPP crystal arthritis cohort (hazard ratio 1.8 [95% confidence interval 1.3–2.3]); results were similar in sensitivity analyses. Conclusion In this first published study of fractures and CPPD, fracture risk was nearly doubled in patients with acute CPP crystal arthritis.
Doctor versus <scp>AI</scp>: Patient and physician evaluation of <scp>LLMs</scp> responses to rheumatology patient questions: comment on the article by Ye et al.
Authors: Gang Wang, Ning Zhuo, Zhichun Liu
Journal: Arthritis & Rheumatology (2024)

Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Rheum at the Table for Everyone: A Call to Expand Rheumatology Knowledge for Primary Care Providers
Authors: Mary E. Margaretten, Jinoos Yazdany, Jennifer Mandal
Journal: Arthritis & Rheumatology (2024)

Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Emerging roles of exosomes in oral diseases progression
Authors: Jiayi Wang, Junjun Jing, Chenchen Zhou, Yi Fan
Journal: International Journal of Oral Science (2024)

Abstract Oral diseases, such as periodontitis, salivary gland diseases, and oral cancers, significantly challenge health conditions due to their detrimental effects on patient’s digestive functions, pronunciation, and esthetic demands. Delayed diagnosis and non-targeted treatment profoundly influence patients’ prognosis and quality of life. The exploration of innovative approaches for early detection and precise treatment represents a promising frontier in oral medicine. Exosomes, which are characterized as nanometer-sized extracellular vesicles, are secreted by virtually all types of cells. As the research continues, the complex roles of these intracellular-derived extracellular vesicles in biological processes have gradually unfolded. Exosomes have attracted attention as valuable diagnostic and therapeutic tools for their ability to transfer abundant biological cargos and their intricate involvement in multiple cellular functions. In this review, we provide an overview of the recent applications of exosomes within the field of oral diseases, focusing on inflammation-related bone diseases and oral squamous cell carcinomas. We characterize the exosome alterations and demonstrate their potential applications as biomarkers for early diagnosis, highlighting their roles as indicators in multiple oral diseases. We also summarize the promising applications of exosomes in targeted therapy and proposed future directions for the use of exosomes in clinical treatment.
Correction: Long non-coding RNA PVT1 promotes tumor progression by regulating the miR-143/HK2 axis in gallbladder cancer
Authors: Jianan Chen, Yan Yu, Hua Li, Qiuyue Hu, Xiaolong Chen, Yuting He, Chen Xue, Fang Ren, Zhigang Ren, Juan Li, Liwen Liu, Zhenfeng Duan, Guangying Cui, Ranran Sun
Journal: Molecular Cancer (2024)

the misused image in Fig. 2K with the correct image • We request to replace the misused images in Fig. 5d and 5i with the correct images • We request to replace the misused image in Fig. 8e with the correct imagesTo ensure the reliability of the experimental conclusion, three repeated experiments were performed again by different authors from their team which has no conflict of interest.The correction does not change the results and scientific conclusions of this article.We sincerely apologize to the editor, reviewers and readers for the errors and any confusion it may have caused.We want to make a correction to this error as soon as possible.
Force-induced Caspase-1-dependent pyroptosis regulates orthodontic tooth movement
Authors: Liyuan Chen, Huajie Yu, Zixin Li, Yu Wang, Shanshan Jin, Min Yu, Lisha Zhu, Chengye Ding, Xiaolan Wu, Tianhao Wu, Chunlei Xun, Yanheng Zhou, Danqing He, Yan Liu
Journal: International Journal of Oral Science (2024)

Abstract Pyroptosis, an inflammatory caspase-dependent programmed cell death, plays a vital role in maintaining tissue homeostasis and activating inflammatory responses. Orthodontic tooth movement (OTM) is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament (PDL) progenitor cells. However, whether and how force induces PDL progenitor cell pyroptosis, thereby influencing OTM and alveolar bone remodeling remains unknown. In this study, we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process. Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively. Using Caspase-1 −/− mice, we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1. Moreover, mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro, which influenced osteoclastogenesis. Mechanistically, transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells. Overall, this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli, indicating a promising approach to accelerate OTM by targeting Caspase-1.
Epigenetic Regulatory Axis <scp>MIR22‐TET3‐MTRNR2L2</scp> Represses <scp>Fibroblast‐Like</scp> Synoviocyte–Mediated Inflammation in Rheumatoid Arthritis
Authors: Yilong Fang, Wei Huang, Xiangling Zhu, Xinming Wang, Xuming Wu, Huihui Wang, Wenming Hong, Shangxue Yan, Lingling Zhang, Yujie Deng, Wei Wei, Jiajie Tu, Chen Zhu
Journal: Arthritis & Rheumatology (2024)

The specific role of fibroblast-like synoviocytes (FLSs) in the pathogenesis of rheumatoid arthritis (RA) is still not fully elucidated. This study aimed to explore the molecular mechanisms of epigenetic pathways, including three epigenetic factors, microRNA (miRNA)-22 (MIR22), ten-eleven translocation methylcytosine dioxygenase 3 (TET3), and MT-RNR2 like 2 (MTRNR2L2), in RA-FLSs.
Porphyrin Derivative with Binary Properties of Photodynamic Therapy and Water‐Dependent Reversible Photoacidity Therapy for Treating Hypoxic Tumor
Authors: Lin Kang, Tianzhen Sun, Shiyang Liu, Hongyou Zhao, Yuxia Zhao
Journal: Advanced Healthcare Materials (2024)

Abstract Porphyrin photosensitizers are the classic drugs in clinical photodynamic therapy (PDT), but the hypoxia of tumor environment and the rapid oxygen consumption of PDT severely weaken their therapeutic effect. A recently reported water‐dependent reversible photoacidity therapy (W‐RPAT) is O 2 ‐independence, providing a solution for the treatment of hypoxic tumors. In this work, TPP‐O‐PEG5, a porphyrin derivative with binary properties of PDT and W‐RPAT, is designed and synthesized for the first time. The nanoparticles (NPs) of TPP‐O‐PEG5 encapsulated with DSPE‐mPEG2000, an amphiphilic polymer approved by Food and Drug Administration, can simultaneously produce reactive oxygen species and H + under irradiation of a 660 nm laser, and revert the H + back under darkness, presenting strong phototoxicity to multiple tumor cell lines with no obvious difference between the IC50 values tested under normoxic (≈20% O 2 ) and hypoxic (&lt;0.5% O 2 ) conditions. Excitingly, in vivo experiments show that the therapeutic effect of TPP‐O‐PEG5 NPs on large hypoxic tumors is better than that of NPe6, a clinical porphin PDT drug. This work provides a novel strategy for porphyrin photosensitizers to break through the limitation of hypoxic environment, and significantly improve the phototherapeutic effect on hypoxic tumors.
Insurance Transitions from Employer-Based Insurance to Medicare and Waitlisting for Kidney Transplantation: Placing Marietta v. DaVita in Context
Authors: Joel T. Adler, Arnold E. Kuk, David C. Cron, Layla Parast, Syed Ali Husain
Journal: Journal of the American Society of Nephrology (2024)

Adler, Joel T.; Kuk, Arnold E.; Cron, David C.; Parast, Layla; Husain, S. Ali Author Information
Evaluating spatially variable gene detection methods for spatial transcriptomics data
Authors: Carissa Chen, Hani Jieun Kim, Pengyi Yang
Journal: Genome biology (2024)

Abstract Background The identification of genes that vary across spatial domains in tissues and cells is an essential step for spatial transcriptomics data analysis. Given the critical role it serves for downstream data interpretations, various methods for detecting spatially variable genes (SVGs) have been proposed. However, the lack of benchmarking complicates the selection of a suitable method. Results Here we systematically evaluate a panel of popular SVG detection methods on a large collection of spatial transcriptomics datasets, covering various tissue types, biotechnologies, and spatial resolutions. We address questions including whether different methods select a similar set of SVGs, how reliable is the reported statistical significance from each method, how accurate and robust is each method in terms of SVG detection, and how well the selected SVGs perform in downstream applications such as clustering of spatial domains. Besides these, practical considerations such as computational time and memory usage are also crucial for deciding which method to use. Conclusions Our study evaluates the performance of each method from multiple aspects and highlights the discrepancy among different methods when calling statistically significant SVGs across diverse datasets. Overall, our work provides useful considerations for choosing methods for identifying SVGs and serves as a key reference for the future development of related methods.
scSNV-seq: high-throughput phenotyping of single nucleotide variants by coupled single-cell genotyping and transcriptomics
Authors: Sarah E. Cooper, Matthew A. Coelho, Magdalena E. Strauss, Aleksander M. Gontarczyk, Qianxin Wu, Mathew J. Garnett, John C. Marioni, Andrew R. Bassett
Journal: Genome biology (2024)

Abstract CRISPR screens with single-cell transcriptomic readouts are a valuable tool to understand the effect of genetic perturbations including single nucleotide variants (SNVs) associated with diseases. Interpretation of these data is currently limited as genotypes cannot be accurately inferred from guide RNA identity alone. scSNV-seq overcomes this limitation by coupling single-cell genotyping and transcriptomics of the same cells enabling accurate and high-throughput screening of SNVs. Analysis of variants across the JAK1 gene with scSNV-seq demonstrates the importance of determining the precise genetic perturbation and accurately classifies clinically observed missense variants into three functional categories: benign, loss of function, and separation of function.