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Quantifying spasticity in individual muscles using shear wave elastography

Radiology Case Reports 2017年第2期12卷 348-352页

作者： Eby, Sarah F. Zhao, Heng Song, Pengfei Vareberg, Barbara J. Kinnick, Randall R. Greenleaf, James F. An, Kai-Nan Brown, Allen W. Chen, Shigao Mayo Medical School Mayo Graduate School Medical Scientist Training Program College of Medicine Mayo Clinic 200 First St. SW Rochester 55905 MN United States Biomechanics Laboratory Division of Orthopedic Research Mayo Clinic 200 First St. SW Rochester 55905 MN United States Department of Biomedical Engineering College of Medicine Mayo Clinic Rochester MN United States Department of Radiology Mayo Clinic Rochester MN United States Department of Physical Medicine and Rehabilitation Mayo Clinic Rochester MN United States

Spasticity is common following stroke;however, high subject variability and unreliable measurement techniques limit research and treatment advances. Our objective was to investigate the use of shear wave elastography (SWE) to characterize the spastic reflex in the biceps brachii during passive elbow extension in an individual with spasticity. The patient was a 42-year-old right-hand-dominant male with history of right middle cerebral artery-distribution ischemic infarction causing spastic left hemiparesis. We compared Fugl-Meyer scores (numerical evaluation of motor function, sensation, motion, and pain), Modified Ashworth scores (most commonly used clinical assessment of spasticity), and SWE measures of bilateral biceps brachii during passive elbow extension. We detected a catch that featured markedly increased stiffness of the brachialis muscle during several trials of the contralateral limb, especially at higher extension velocities. SWE was able to detect velocity-related increases in stiffness with extension of the contralateral limb, likely indicative of the spastic reflex. This study offers optimism that SWE can provide a rapid, real-time, quantitative technique that is readily accessible to clinicians for evaluating spasticity. © 2017 The Authors

关键词： Muscle spasticity Skeletal muscle Stroke Ultrasound Upper extremity

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Ethics and research assessing the relative roles of genes and the environment

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Accountability in Research 2004年第3-4期11卷 161-182页

作者： DeCamp, Matthew Sugarman, Jeremy Duke University Medical Scientist Training Program School of Medicine and Department of Philosophy Durham NC United States Phoebe R. Berman Bioethics Institute Johns Hopkins University Baltimore MD United States

Research on the interaction of genes and the environment is revealing that many human diseases have both genetic and environmental components. Even traditional "environmental" diseases, such as infections, appear to interact with genetic components in the human host. Environmental genetics research will inevitably increase understanding of individual susceptibilities to toxic exposures in the environment and harmful side effects of medications;therefore, it has great promise for improving the prevention and treatment of human diseases. However, realizing the benefits of this research requires careful attention to ethical issues that are particularly relevant in this context. This article reviews some of the most pressing issues related to research design and methods, as well as from the application of research results (e.g., workplace genetic screening and legal toxic torts, personal medical responsibility, and the relationship between genetics and public health measures). © Taylor & Francis Inc.

关键词： Environmental genetics Ethics Genetic research Population genetics Research standards Research subjects

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Immune checkpoint expression and relationships to anti-PD-L1 immune checkpoint blockade cancer immunotherapy efficacy in aged versus young mice

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Aging and Cancer 2022年第1期3卷 68-83页

作者： Garcia, Myrna G. Deng, Yilun Murray, Clare Reyes, Ryan M Padron, Alvaro Bai, Haiyan Kancharla, Aravind Gupta, Harshita Shen-Orr, Shai Curiel, Tyler J. South Texas Medical Scientist Training Program University of Texas Health San Antonio TX United States Graduate School of Biomedical Sciences University of Texas Health San Antonio TX United States Department of Medicine University of Texas Health San Antonio TX United States Senda Biosciences Cambridge MA United States Technion Israel Institute of Technology Haifa Israel Clayton Foundation for Research Houston TX United States Mays Cancer Center University of Texas Health San Antonio TX United States

Introduction: Aging is the biggest cancer risk, and immune checkpoint (IC) inhibition (ICI) is a revolutionary cancer immunotherapy approach. Nonetheless, there are limited preclinical/clinical data regarding aging effects on ICI outcomes or age effects on IC expression in different organs or tumors. Methods: Flow cytometry assessed IC on immune and non-immune cells in various organs in young and aged BL6 mice. Comparisons: aged versus young naïve WT versus interferon-γ^KO mice and WT challenged with B16F10 melanoma and treated with αPD-1 or αPD-L1 ICI. We co-cultured young and aged T cells and myeloid cells in vitro and used OMIQ analyses to test cell–cell interactions. Results: αPD-1 ICI treated melanoma in young and aged hosts, whereas αPD-L1 ICI was only effective in young. We found considerable, previously undescribed age effects on expression of various IC molecules participating in the ICI treatment, including PD-1, PD-L1, PD-L2, and CD80, in distinct organs and in the tumor. These data help explain differential ICI efficacy in young and aged hosts. Host interferon-γ influenced age effects on IC expression in both directions depending on specific IC molecule and tissue. IC expression was further affected by tumor challenge on immune, non-immune, and tumor cells in tumor and other organs. In in vitro co-culture, αPD-1 versus αPD-L1 distinctly influenced polyclonal T cells in young versus aged, suggesting mechanisms for distinct age-related ICI outcomes. Conclusion: Age affects IC expression on specific immune cells in an organ- and tissue-specific manner. ICs were generally higher on aged immune cells. High immune-cell PD-1 could help explain αPD-1 efficacy in aged. High co-expression of CD80 with PD-L1 on dendritic cells could help explain lack of αPD-L1 efficacy in aged hosts. Factors other than myeloid cells and interferon-γ also affect age-related IC expression and T cell function, meriting additional studies. © 2022 The Authors. Aging and Cancer

关键词： age cancer immunotherapy immune checkpoints interferon-γ PD-1 PD-L1

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A Graduate-Level Interdisciplinary Curriculum in CAR-T Cell Therapy

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Mayo Clinic Proceedings: Innovations, Quality and Outcomes 2020年第2期4卷 203-210页

作者： Sterner, Rosalie M. Hedin, Karen E. Hayden, Richard E. Nowakowski, Grzegorz S. Wyles, Saranya P. Greenberg-Worisek, Alexandra J. Terzic, Andre Kenderian, Saad S. Mayo Clinic Medical Scientist Training Program Mayo Clinic College of Medicine and Science Rochester MN United States Department of Immunology Mayo Clinic Rochester MN United States Otorhinolaryngology Mayo Clinic Scottsdale AZ United States Division of Hematology Department of Medicine Mayo Clinic Rochester MN United States Department of Dermatology Mayo Clinic Rochester MN United States Center for Regenerative Medicine Mayo Clinic Rochester MN United States Department of Cardiology Mayo Clinic Rochester MN United States

Objective: To evaluate the impact of a novel interdisciplinary graduate-level course in chimeric antigenic receptor-T cell therapy on students’ knowledge and interests in translational science. Materials/Participants and Methods: The course ran November 12 to 16, 2018. Students were surveyed before and after the course. The survey included questions regarding background, self-perceived knowledge/confidence in skills, and interests/predicted behaviors. Students were assigned to work in collaborative interdisciplinary teams to develop a research proposal. Results: A total of 25 students taking the course for graduate-level credit were surveyed. Of these, all 25 (100%) completed the surveys. Students came from variable backgrounds and were at different stages of graduate training. After completion of the course, there was a statistically significant increase in self-perceived knowledge of immunotherapy (mean score of 3.6 postcourse vs 2.6 precourse, on a 5-point Likert scale;P<.001), knowledge of the bench to clinic translational process (3.7 postcourse vs 3.0 precourse;P<.001), confidence in critical reading skills (4.3 postcourse vs 4.0 precourse;P=.008), confidence in immunotherapy-focused grant writing skills (3.6 postcourse vs 2.8 precourse;P<.001), and interest in working in interdisciplinary teams (4.8 postcourse vs 4.6 precourse;P=.02). Conclusion: The structure of this innovative and comprehensive course serves as a platform for educational courses in interdisciplinary translational research and helps trainees build knowledge and interest in the fields of chimeric antigenic receptor-T cells, regenerative sciences, and immunotherapy. © 2019 Mayo Foundation for medical Education and Research

关键词： CAR-T cell, chimeric antigenic receptor-T cell CME, continuing medical education FDA, US Food and Drug Administration GMP, good manufacturing practice MCGSBS, Mayo Clinic Graduate School of Biomedical Sciences S, satisfactory

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Dynamic transcriptomic m6A decoration: writers, erasers, readers and functions in RNA metabolism

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细胞研究（英文版） 2018年第6期28卷 616-624页

作者： Ying Yang Phillip J.Hsu Yu-Sheng Chen Yun-Gui Yang CAS Key Laboratory of Genomic and Precision Medicine Collaborative Innovation Center of Genetics and Development College of Future Technology Beijing Institute of Genomics Chinese Academy of Sciences Beijing 100101 China University of Chinese Academy of Sciences Beijing 100049 China Institute of Stem Cell and Regeneration Chinese Academy of Sciences Beijing 100101 China Department of Chemistry and Institute for Biophysical Dynamics Howard Hughes Medical Institute The University of Chicago Chicago IL 60637 USA Medical Scientist Training Program/Committee on Immunology The University of Chicago Chicago IL 60637 USA CAS Key Laboratory of Genomic and Precision Medicine Collaborative Innovation Center of Genetics and Development College of Future Technology Beijing Institute of Genomics Chinese Academy of Sciences Beijing 100101 China University of Chinese Academy of Sciences Beijing 100049 China

N6-methyladenosine (m6A) is a chemical modification present in multiple RNA species,being most abundant in *** on enzymes or factors that catalyze,recognize,and remove m6A have revealed its comprehensive roles in almost every aspect of mRNA metabolism,as well as in a variety of physiological *** review describes the current understanding of the m6A modification,particularly the functions of its writers,erasers,readers in RNA metabolism,with an emphasis on its role in regulating the isoform dosage of mRNAs.

关键词： Methylation analysis RNA modification

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43852 JAK inhibitor safety compared to traditional systemic immunosuppressive therapies

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Journal of the American Academy of Dermatology 2023年第3期89卷 AB60-AB60页

作者： Bunick, Christopher, MD, PhD Daniele, Stefano, PhD Department of Dermatology and Program in Translational Biomedicine Yale University Medical Scientist Training Program Yale School of Medicine

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Crystal structure of the YTH domain of YTHDF2 reveals mechanism for recognition of N6-methyladenosine

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细胞研究（英文版） 2014年第12期24卷 1493-1496页

作者： Tingting Zhu Ian A Roundtree Ping Wang Xiao Wang Li Wang Chang Sun Yuan Tian Fudan University Shanghai Cancer Center Department of Oncology and Institute of Biomedical Sciences and School of Basic Medical SciencesShanghai Medical College of Fudan University Shanghai 200032 China Medical Scientist Training Program and Department of Biochemistry and Molecular Biology The University of Chicago Chicago IL 60637 USA Department of Chemistry and Institute for Biophysical Dynamics The University of Chicago Chicago IL 60637 USA Howard Hughes Medical Institute The University of Chicago Chicago IL 60637 USA

Dear Editor,N6-methyladenosine (m6A) has been demonstrated to be ubiquitous in several types of eukaryotic RNAs,including messenger RNA (mRNA),transfer RNA (tRNA),ribosomal RNA (rRNA),long non-coding RNA (lncRNA),and small nuclear RNA (snRNA) [1].The recent discoveries of RNA m6A methyltransferase complex METTL3/METTL14/WTAP and demethylases FTO and ALKBH5 prove the reversibility of m6A modification [2-6].

关键词： @@

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Updating Clinical Risk Stratification Models Using Rank-Based Compatibility: Approaches for Evaluating and Optimizing Clinician-Model Team Performance

arXiv

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arXiv 2023年

作者： Ötles, Erkin Denton, Brian T. Wiens, Jenna Medical Scientist Training Program University of Michigan Ann ArborMI United States Department of Industrial and Operations Engineering University of Michigan Ann ArborMI United States Division of Computer Science and Engineering University of Michigan Ann ArborMI United States

As data shift or new data become available, updating clinical machine learning models may be necessary to maintain or improve performance over time. However, updating a model can introduce compatibility issues when the behavior of the updated model does not align with user expectations, resulting in poor user-model team performance. Existing compatibility measures depend on model decision thresholds, limiting their applicability in settings where models are used to generate rankings based on estimated risk. To address this limitation, we propose a novel rank-based compatibility measure, CR, and a new loss function that aims to optimize discriminative performance while encouraging good compatibility. Applied to a case study in mortality risk stratification leveraging data from MIMIC, our approach yields more compatible models while maintaining discriminative performance compared to existing model selection techniques, with an increase in CR of 0.019 (95% confidence interval: 0.005, 0.035). This work provides new tools to analyze and update risk stratification models used in clinical care. © 2023, CC BY.

关键词： Risk assessment

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An efficient approximation for the real-time implementation of the Mixture of Trajectory Models decoder

An efficient approximation for the real-time implementation ...

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IEEE Biomedical Circuits and Systems (BIOCAS)

作者： William Bishop Byron M. Yuy Gopal Santhanam Afsheen Afshar Stephen I. Ryu Krishna V. Shenoy The Johns Hopkins University Applied Physics Laboratory Laurel Maryland USA Department of Electrical Engineering Standford University California USA Department of Electrical Engineering Stanford University Stanford California USA Medical Scientist Training Program Stanford University Stanford California Department of Neurosurgery Stanford University Stanford California Neurosciences Program Stanford University Stanford California

The mixture of trajectory models (MTM) decoder has been used to reconstruct arm trajectories from neural activity. While it produces reasonable results, the computational demands of previously published versions may be too high for many real-time systems. We have developed a novel method of approximating the MTM state posteriors that does not require the use of Newtonpsilas method. We show that this method results in only a small decrease in decoding performance yet reduces computational cost by 56.4%. Additionally, an MTM algorithm using this method of approximating the state posteriors produces more accurate decoded trajectories when using small bin sizes than an MTM algorithm using a Gaussian observation model. The more efficient formulation of the MTM algorithm presented here provides an alternative approximation of this algorithm for use on resource constrained embedded systems.

关键词： Decoding Newton method Iterative algorithms Laboratories Physics computing Real time systems Approximation algorithms Biomedical engineering Neurosurgery Educational institutions

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High-Throughput Co-Culture System for Analysis of Spatiotemporal Cell-Cell Signaling

SSRN

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SSRN 2022年

作者： Son, Minjun Wang, Andrew G. Kenna, Emma Tay, Savaş Pritzker School of Molecular Engineering University of Chicago ChicagoIL60637 United States Institute for Genomics and Systems Biology University of Chicago ChicagoIL60637 United States Medical Scientist Training Program University of Chicago ChicagoIL60637 United States

Study of spatial and temporal aspects of signaling between individual cells is essential in understanding development, the immune response, and host-pathogen interactions. We present an automated high-throughput microfluidic platform that chemically stimulates immune cells to initiate cytokine secretion, and controls the formation of signal gradients that activate neighboring cell populations. Furthermore, our system enables controlling the cell type and density based on distance, and retrieval of cells from different regions for gene expression analysis. Our device performs these tasks in 192 independent chambers to simultaneously test different co-culture conditions. We demonstrate these capabilities by creating various cellular communication scenarios between macrophages and fibroblasts in vitro. We find that spatial distribution of macrophages and heterogeneity in cytokine secretion determine spatiotemporal gene expression responses. Furthermore, we describe how gene expression dynamics depend on a cell’s distance from the signaling source. Our device addresses key challenges in the study of cell-to-cell signaling, and provides high-throughput and automated analysis over a wide range of culture conditions. © 2022, The Authors. All rights reserved.

关键词： Macrophages

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