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Skin Staphylococcus aureus detection and relationship to atopic dermatitis outcomes using culture and metagenomic sequencing

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Scientific Reports 2025年第1期15卷 1-13页

作者： Arya Dahal Wan Chi Chang Elisabet Johansson Brittany Grashel David Morgan Lindsey Williams Mindy Hammonds Seiya Sachdeva Dan Spagna Latha Satish Jocelyn M. Biagini Gurjit K. Khurana Hershey Lisa J. Martin David B. Haslam Nicholas J. Ollberding Division of Asthma Research Cincinnati Children’s Hospital Medical Center 3333 Burnet Avenue MLC 7037 Cincinnati OH 45229 USA Medical Scientist Training Program University of Cincinnati College of Medicine Cincinnati OH 45229 USA Department of Pediatrics University of Cincinnati College of Medicine Cincinnati OH 45229 USA Division of Human Genetics Cincinnati Children’s Hospital Medical Center Cincinnati OH 45229 USA Microbial Genomics and Metagenomics Laboratory Cincinnati Children’s Hospital Medical Center Cincinnati OH 45229 USA Division of Biostatistics and Epidemiology Cincinnati Children’s Hospital Medical Center Cincinnati OH 45229 USA

Staphylococcus aureus(SA) skin colonization in pediatric atopic dermatitis (AD) increases risk for severe AD and development of other allergic diseases. Despite this, there is no consensus regarding the optimal method to detectSA. Studies comparing metagenomic shotgun sequencing (MSS) and culture-based methods inSAdetection and relationships to AD outcomes are lacking. In the Mechanisms of Progression of Atopic Dermatitis to Asthma in Children (MPAACH) cohort, we definedSAcolonization categories by contact agar plate sampling/culture and skin tape sampling/MSS: double negative, sequencing only positive, contact plate only positive, and double positive (n= 759). We assessed AD severity, sensitization, total IgE, and atopic outcomes across categories. Culture missed 69% of samples detected by MSS and MSS missed 54% of samples detected by culture. The double positive group exhibited higher AD severity, sensitization load, and total serum IgE, and was more likely to develop allergic rhinitis (AR) compared to other groups. Detection ofSAby MSS or culture missed over half of theSAdetected by the other method. Importantly, detection via both methods correlated with increased AD severity, sensitization, total IgE, and AR. Thus, these methods are complementary and both may be necessary for comprehensive evaluation ofSAand its clinical and biologic impact.

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Semiautomatic image analysis for grain counting in in situ hybridization experiments

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NeuroImage 1994年第3期1卷 163-172页

作者： Mize, R. Ranney Thouron, Carol Lucas, Louis Harlan, Richard Department of Anatomy Neurosci. Ctr. Comp. Imaging Lab. Louisiana State Univ. Medical Center New Orleans LA 70112 United States Department of Anatomy Neuroscience Training Program Tulane University Medical Center New Orleans LA 70112 United States

We have developed a computer image analysis procedure for counting autoradiographic grains in in situ hybridization experiments. The procedure automatically estimates the number of autoradiographic grains over cells and measures cell number and size so that grain density per unit cell area can be calculated. Advantages include the clear separation of grains and cells, using chromatic and spatial filters to enhance the image;the use of gray level operators to extract cells from grains;and the use of binary operators for separating apposed or partially overlapping cells and grains. Comparison of manual and automated grain counts revealed a significant correlation between human and computer estimations of grain number. However, the automatic grain counting techniques consistently underestimated the number of grains when grain density was high. Measures of the fractional area occupied by grains normalized by the average area of a single grain were a better estimate at high grain densities. The procedure can be modified easily to operate on most image analyzers. © 1994 Academic Press. All rights reserved.

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Olfactory dysfunction and COVID-19

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Operative Techniques in Otolaryngology - Head and Neck Surgery 2022年第2期33卷 141-146页

作者： Choi, Rhea Gupta, Rupali Finlay, John B. Goldstein, Bradley J. Department of Head and Neck Surgery & Communication Sciences Duke University School of Medicine Durham 27710 NC United States Medical Scientist Training Program Duke University School of Medicine Durham NC United States Department of Neurobiology Duke University School of Medicine Durham NC United States

Here, we provide an overview of olfactory dysfunction associated with COVID-19. We provide background regarding the organization and function of the peripheral olfactory system. A review of the relevant literature on anosmia and parosmia due to infection with SARS-CoV-2, the virus causing COVID-19, is provided. Specific attention is focused on possible mechanisms by which the virus may interact with and damage the cell populations of peripheral olfactory system. Evidence from human studies as well as animal models is considered. Finally, we discuss current recommendations for evaluation and management of patients with persistent post-COVID olfactory dysfunction, as well as possible future research directions. © 2022

关键词： COVID-19 Olfaction Olfactory dysfunction

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Learning deep attribution priors based on prior knowledge

arXiv

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arXiv 2019年

作者： Weinberger, Ethan Janizek, Joseph Lee, Su-In Paul G. Allen School of Computer Science and Engineering University of Washington Medical Scientist Training Program University of Washington

Feature attribution methods are an essential tool for understanding the behavior of complex deep learning models. However, ensuring that models produce meaningful explanations, rather than ones that rely on noise, is not straightforward. Exacerbating this problem is the fact that attribution methods do not provide insight as to why features are assigned their attribution values, leading to explanations that are difficult to interpret. In real-world problems we often have sets of additional information for each feature that are predictive of that feature's importance to the task at hand. Here we propose the deep attribution prior (DAPr) framework to exploit such information to overcome the limitations of attribution methods. Our framework jointly learns a relationship between prior information and feature importance, as well as biases models to have explanations that rely on features predicted to be important. We find that our framework both results in networks that generalize better to out of sample data and admits new methods for interpreting model explanations. Copyright © 2019, The Authors. All rights reserved.

关键词： Deep learning

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Updating Clinical Risk Stratification Models Using Rank-Based Compatibility: Approaches for Evaluating and Optimizing Clinician-Model Team Performance 8

Updating Clinical Risk Stratification Models Using Rank-Base...

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8th Machine Learning for Healthcare Conference, MLHC 2023

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 E. Ötles., B.T. Denton & J. Wiens.

关键词： Risk assessment

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In vivo photothermal reconfiguration of liquid crystalline elastomer nanocomposites

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Cell biomaterials 2025年第2期1卷 100022页

作者： Nathaniel P Skillin Bruce E Kirkpatrick Nicole E Friend Amy R Perry Joselle M McCracken Melvin Colorado Escobar Benjamin R Nelson Nathaniel L Day Patrick S Hume Taufiek Konrad Rajab Kristi S Anseth Timothy J White Department of Chemical and Biological Engineering University of Colorado Boulder Boulder CO 80303 USA. The BioFrontiers Institute University of Colorado Boulder Boulder CO 80303 USA. Medical Scientist Training Program School of Medicine University of Colorado Anschutz Medical Campus Aurora CO 80045 USA. Department of Molecular Cellular and Developmental Biology University of Colorado Boulder Boulder CO 80303 USA. Materials Science and Engineering Program University of Colorado Boulder Boulder CO 80303 USA. Department of Medicine National Jewish Health Denver CO 80206 USA. Department of Cardiovascular Surgery Arkansas Children's Hospital Little Rock AR 72202 USA. Lead contact.

medical implants with fixed geometry have many clinical applications but are limited by the dynamic nature of human physiology. To overcome this barrier, focus has shifted to stimuli-responsive materials capable of changing their geometry on demand, such as liquid crystalline elastomers (LCEs). Here, we report on the development and biological performance of LCE-gold nanorod (LCE-AuNR) nanocomposites engineered for use in optically reconfigurable medical devices. First, we maximized the strain response and force output of 3D-printed LCE-AuNR within a physiologically relevant temperature window of 37°C-50°C. LCE-AuNR are shown to be cytocompatible and induce a comparable foreign body response to medical grade silicone when implanted subcutaneously in mice. Upon transcutaneous near-infrared irradiation, implanted LCE-AuNR exhibit rapid and reversible photothermal actuation. Furthermore, controlled photothermal actuation does not result in the pathology of adjacent tissues. This approach opens new horizons for designing dynamic medical implants across a wide range of clinical applications.

关键词： liquid crystalline elastomer gold nanorod photothermal foreign body response adjustable medical device transcutaneous stimulation

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Single-Cell RNA Sequencing Identifies Expression Patterns Associated with Clinical Responses to Dual-Targeted CAR-T Cell Therapy

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BLOOD 2020年 136卷 33-34页

作者： Kearl, Tyce Mei, Ao Brown, Ryan Johnson, Bryon Schneider, Dina Dropulic, Boro Hari, Parameswaran Shah, Nirav N. Malarkannan, Subramaniam Division of Hematology Oncology and Bone Marrow Transplantation Department of Pediatrics Medical College of Wisconsin Milwaukee WI Blood Research Institute Versiti Milwaukee WI Department of Microbiology and Immunology Medical College of Wisconsin Milwaukee WI Medical Scientist Training Program Medical College of Wisconsin Milwaukee WI Division of Hematology and Oncology Department of Medicine Medical College of Wisconsin Milwaukee WI Lentigen Technology Inc. a Miltenyi Biotec Company Gaithersburg MD

INTRODUCTION Chimeric Antigen Receptor (CAR)-T cell therapy is emerging as a powerful treatment for relapsed or refractory B cell lymphomas. However, a variety of escape mechanisms prevent CAR-T cell therapy from being more uniformly effective. To better understand mechanisms of CAR-T failure among patients treated with dual-targeted CAR-T cells, we performed single-cell RNA sequencing of samples from a Phase 1 trial (NCT03019055). The clinical trial used anti-CD20, anti-CD19 CAR-T cells for the treatment of relapsed/refractory B-cell non-Hodgkin Lymphoma. Clinical responses from this study are reported independently (Shah et al. in press in Nat Med ). While robust clinical responses occurred, not all patients had similar outcomes. In single-antigen specific CAR-T cells, mechanisms of resistance include antigen down-regulation, phenotype switch, or PD-1 inhibition (Song et al. Int J Mol Sci 2019). However, very little is understood about the mechanisms of failure that are specific to dual-targeted CAR-T cells. Interestingly, loss of CD19 antigen was not observed in treatment failures in the study. METHODS De-identified patient samples were obtained as peripheral blood mononuclear cells on the day of harvest (“pre” samples), at the peak of in vivo CAR-T cell expansion which varied from day 10 to day 21 after infusion (“peak” samples), and on day 28 post-infusion (“d28” samples). The CAR-T cell infusion product was obtained on day 14 of on-site manufacturing (“product” samples). All samples were cryopreserved and single cell preparation was performed with batched samples using 10X Genomics kits. Subsequent analysis was performed in R studio using the Seurat package (Butler et al. Nat Biotech 2018) with SingleR being used to identify cell types in an unbiased manner (Aran et al. Nat Immunol 2019). RESULTS We found that distinct T cell clusters were similarly represented in the responder and non-responder samples. The patients' clinical responses did not depend on the l

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Roles for the chromatin remodeler CHD7 in CNS patterning and neural stem cell proliferation and differentiation

Roles for the chromatin remodeler CHD7 in CNS patterning and...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Mark Durham Jennifer M.Skidmore Hui Yao Donna M.Martin Medical Scientist Training Program Baylor College of Medicine Departments of Pediatrics The University of Michigan Medical School Human Genetics The University of Michigan Medical School

Impairments in central nervous system(CNS) processing of peripheral sensory functions(vision, hearing, balance and olfaction) are common in autism spectrum disorders(ASDs). CHARGE syndrome, a congenital anomaly disorder and leading cause of multisensory impairment and deafblindness, is one genetic form of ASD. The underlying mechanisms leading to ASD behaviors in CHARGE are not known;however, CNS developmental abnormalities including arrhinencephaly, holoprosencephaly, corpus callosum defects and cerebellar defects are common. CHARGE is caused by heterozygous loss of CHD7, an ATP dependent chromodomain nucleosome remodeling protein that regulates gene expression. Chd7 heterozygous mutant mice exhibit defects in development of inner ear and craniofacial structures similar to those in humans with CHARGE. In mice, Chd7 is expressed in the developing and mature brain regions(olfactory bulb, hypothalamus, midbrain, hindbrain, and cerebellum), and in areas of adult neurogenesis(dentate gyrus of the hippocampus and subventricular zone). Prior studies identified roles for Chd7 in neurogenesis in the developing mouse inner ear and olfactory placode, where CHD7 is expressed in neural stem cells and regulates proneural gene expression, and in the CNS forebrain subventricular zone, where CHD7 regulates neural stem cell proliferation and fate. Here we present data from conditional mice with loss of one or both copies of in the brain. Nestin-Cre-mediated Chd7 deletion led to mild anxiety phenotypes, whereas Wnt1Cre-mediated conditional deletion of Chd7 in the midbrain/hindbrain was postnatal lethal and resulted in cerebellar hypoplasia and reduced foliation in postnatal day 1 cerebella. Loss of Chd7 by Wnt1-Cre also led to attenuation of Wnt1 and Fgf8 expression domains at the embryonic day 11.5 midbrain/hindbrain boundary, consistent with roles for Chd7 in early midbrain-hindbrain patterning. Our results provide novel insights into roles for Chd7 in cerebellar development, and s

关键词： CHD Roles for the chromatin remodeler CHD7 in CNS patterning and neural stem cell proliferation and differentiation CNS

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In Regard to Ebrahimi et al.

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International Journal of Radiation Oncology Biology Physics 2023年第5期117卷 1297-1298页

作者： Ebner, Daniel K. Kloeber, Jake A. Malouff, Timothy D. Department of Radiation Oncology Mayo Clinic RochesterMinnesota United States Department of Radiation Oncology Mayo Clinic Rochester Minnesota Mayo Clinic Medical Scientist Training Program Mayo Clinic RochesterMinnesota United States Department of Radiation Oncology OU Health Stephenson Cancer Center Oklahoma CityOK United States

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HA-996 (1-hydroxy-3-aminopyrrolidone-2) selectively reduces N-methyl-d-aspartate (NMDA)-mediated brain damage

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neuroscience Letters 1989年第1-2期104卷 167-170页

作者： McDonald, John W. Uckele, John Silverstein, Faye S. Johnston, Michael V. Neuroscience and Medical Scientist Training Program University of Michigan Medical School Ann Arbor MI United States Department of Pediatrics University of Michigan Medical School Ann Arbor MI United States Department of Neurology University of Michigan Medical School Ann Arbor MI United States Department of Neurology The Johns Hopkins University School of Medicine the Kennedy Institute Baltimore MD United States Department of Pediatrics The Johns Hopkins University School of Medicine the Kennedy Institute Baltimore MD United States

The neuroprotective effects of the strychnine-insensitive glycine receptor antagonist, HA-966, against N-methyl-d-aspartate (NMDA)- and quisqualate (QA)-mediated brain injury were determined in perinatal rats. Postnatal day (PND) 7 rats received intrastriatal injections of NMDA (25 nmol) or QA (100 nmol) and then were administered intraperitoneal (i.p.) injections of varying doses of HA-966 or vehicle 15 min later. Animals were sacrificed 5 days later and the degree of brain injury was calculated by comparison of the weights of injected and contralateral cerebral hemispheres. HA-966 selectively reduced the degree of NMDA-mediated brain injury in a dose-dependent manner. However, HA-966 did not attenuate QA-mediated brain injury. © 1989.

关键词： MK-801 N-Methyl-d-aspartate Neuroprotection Neurotoxicity Phencyclidine Rat brain Strychnine-insensitive glycine receptor

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