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Abstract Progressive supranuclear palsy (PSP), a rare Parkinsonian disorder, is characterized by problems with movement, balance, and cognition. PSP differs from Alzheimer’s disease (AD) and other diseases, displaying abnormal microtubule-associated protein tau by both neuronal and glial cell pathologies. Genetic contributors may mediate these differences; however, the genetics of PSP remain underexplored. Here we conduct the largest genome-wide association study (GWAS) of PSP which includes 2779 cases (2595 neuropathologically-confirmed) and 5584 controls and identify six independent PSP susceptibility loci with genome-wide significant (P

Optogenetic gene therapies offer a promising strategy for restoring vision to patients with retinal degenerative diseases, such as retinitis pigmentosa (RP). Several clinical trials have begun in this area using different vectors and optogenetic proteins (Clinical Identifiers: NCT02556736, NCT03326336, NCT04945772, and NCT04278131). Here we present preclinical efficacy and safety data for the NCT04278131 trial, which uses an AAV2 vector and Chronos as the optogenetic protein. Efficacy was assessed in mice in a dose-dependent manner using electroretinograms (ERGs). Safety was assessed in rats, nonhuman primates, and mice, using several tests, including immunohistochemical analyses and cell counts (rats), electroretinograms (nonhuman primates), and ocular toxicology assays (mice). The results showed that Chronos-expressing vectors were efficacious over a broad range of vector doses and stimulating light intensities, and were well tolerated: no test article-related findings were observed in the anatomical and electrophysiological assays performed.

The buildings in which people work, live, and spend their leisure time are increasingly embedded with sophisticated information technology (IT). This article describes the approach of Metropolitan Community College (MCC) in Omaha, Nebraska of the United States to provide an occupational context to some of their IT coursework by organizing IT instruction around the context of building automation systems (BAS). This contextualization allows IT students not only to study IT as a standalone discipline but also to study its integrated use within a specific occupational context. The article also describes MCC's focused curriculum design efforts funded by the National Science Foundation's Advanced Technological Education program. These efforts toward BAS-contextualization of the IT curriculum have become a catalyst for systematic contextualization of IT instruction at MCC and support the institution's broader efforts to become a national model in IT instruction and interdisciplinary engagement within the United States. The research-based approach, activities, and outcomes of this project are all described here, as well as the lessons learned by one community college seeking to make their IT program increasingly relevant to their students and the IT workforce of today.

Optogenetics is a new approach for controlling neural circuits with numerous applications in both basic and clinical science. In retinal degenerative diseases, the photoreceptors die, but inner retinal cells remain largely intact. By expressing light sensitive proteins in the remaining cells, optogenetics has the potential to offer a novel approach to restoring vision. In the past several years, optogenetics has advanced into an early clinical stage, and promising results have been reported. At the current stage, there is an urgent need to develop hardware and software for clinical training, testing, and rehabilitation in optogenetic therapy, which is beyond the capability of existing ophthalmic equipment. In this paper, we present an engineering platform consisting of hardware and software utilities, which allow clinicians to interactively work with patients to explore and assess their vision in optogenetic treatment, providing the basis for prosthetic design, customization, and prescription. This approach is also applicable to other therapies that utilize light activation of neurons, such as photoswitches.Clinical and Translational Impact Statement–The engineering platform allows clinicians to conduct training, testing, and rehabilitation in optogenetic gene therapy for retinal degenerative diseases, providing the basis for prosthetic design, customization, and prescription.

Background: Porphyria cutanea tarda (PCT) is a complex metabolic disease resulting from altered activity of the enzyme uroporphyrinogen decarboxylase (UROD) in the liver resulting in accumulation of uroporphyrin. PCT presents as a blistering photodermatitis with skin fragility, vesicles, scarring and milia. Case: We report a case of PCT in a 67-year-old man with hemochromatosis (HFE) gene mutation who, following a major syncopal episode in response to venesection was commenced on low dose hydroxychloroquine. Conclusions: Low dose hydroxychloroquine provided a safe and effective alternative to venesection in this patient who was needle phobic.

Abstract The global surge in COVID-19 cases underscores the need for fast, scalable, and reliable testing. Current COVID-19 diagnostic tests are limited by turnaround time, limited availability, or occasional false findings. Here, we developed a machine learning-based framework for predicting individual COVID-19 positive diagnosis relying only on readily-available baseline data, including patient demographics, comorbidities, and common lab values. Leveraging a cohort of 31,739 adults within an academic health system, we trained and tested multiple types of machine learning models, achieving an area under the curve of 0.75. Feature importance analyses highlighted serum calcium levels, temperature, age, lymphocyte count, smoking, hemoglobin levels, aspartate aminotransferase levels, and oxygen saturation as key predictors. Additionally, we developed a single decision tree model that provided an operable method for stratifying sub-populations. Overall, this study provides a proof-of-concept that COVID-19 diagnosis prediction models can be developed using only baseline data. The resulting prediction can complement existing tests to enhance screening and pandemic containment workflows.

Background: Porphyria cutanea tarda (PCT) is a complex metabolic disease resulting from altered activity of the enzyme uroporphyrinogen decarboxylase (UROD) in the liver resulting in accumulation of uroporphyrin. PCT presents as a blistering photodermatitis with skin fragility, vesicles, scarring and milia. Case: We report a case of PCT in a 67-year-old man with hemochromatosis (HFE) gene mutation who, following a major syncopal episode in response to venesection was commenced on low dose hydroxychloroquine. Conclusions: Low dose hydroxychloroquine provided a safe and effective alternative to venesection in this patient who was needle phobic.

Despite extraordinary international efforts to dampen the spread and understand the mechanisms behind SARS-CoV-2 infections, accessible predictive biomarkers directly applicable in the clinic are yet to be discovered. Recent studies have revealed that diverse types of assays bear limited predictive power for COVID-19 outcomes. Here, we harness the predictive power of chest computed tomography (CT) in combination with plasma cytokines using a machine learning and k-fold cross-validation approach for predicting death during hospitalization and maximum severity degree in COVID-19 patients. Patients (n = 152) from the Mount Sinai Health System in New York with plasma cytokine assessment and a chest CT within five days from admission were included. Demographics, clinical, and laboratory variables, including plasma cytokines (IL-6, IL-8, and TNF-α), were collected from the electronic medical record. We found that CT quantitative alone was better at predicting severity (AUC 0.81) than death (AUC 0.70), while cytokine measurements alone better-predicted death (AUC 0.70) compared to severity (AUC 0.66). When combined, chest CT and plasma cytokines were good predictors of death (AUC 0.78) and maximum severity (AUC 0.82). Finally, we provide a simple scoring system (nomogram) using plasma IL-6, IL-8, TNF-α, ground-glass opacities (GGO) to aerated lung ratio and age as new metrics that may be used to monitor patients upon hospitalization and help physicians make critical decisions and considerations for patients at high risk of death for COVID-19.

BackgroundDisparate COVID-19 outcomes have been observed between Hispanic, non-Hispanic Black, and White patients. The underlying causes for these disparities are not fully understood.MethodsThis was a retrospective study utilizing electronic medical record data from five hospitals within a single academic health system based in New York City. Multivariable logistic regression models were used to identify demographic, clinical, and lab values associated with in-hospital mortality.ResultsA total of 3,086 adult patients with self-reported race/ethnicity information presenting to the emergency department and hospitalized with COVID-19 up to April 13, 2020, were included in this study. While older age (multivariable odds ratio (OR) 1.06, 95% CI 1.05–1.07) and baseline hypoxia (multivariable OR 2.71, 95% CI 2.17–3.36) were associated with increased mortality overall and across all races/ethnicities, non-Hispanic Black (median age 67, interquartile range (IQR) 58–76) and Hispanic (median age 63, IQR 50–74) patients were younger and had different comorbidity profiles as compared to non-Hispanic White patients (median age 73, IQR 62–84; p < 0.05 for both comparisons). Among inflammatory markers associated with COVID-19 mortality, there was a significant interaction between the non-Hispanic Black population and interleukin-1-beta (interaction p-value 0.04).ConclusionsThis analysis of a multiethnic cohort highlights the need for inclusion and consideration of diverse populations in ongoing COVID-19 trials targeting inflammatory cytokines.

Introduction:. The shift from in-person visits to telehealth visits during the COVID-19 pandemic presented unique challenges for patients with pain. Disparities in health care access already existed, and the impact of telehealth on these inequities has not been studied. Objectives:. To identify sociodemographic characteristics of patients with pain obtaining care through video, telephone, and in-person visits as social distancing restrictions evolved during the COVID-19 pandemic. Methods:. Using our institutional clinical data warehouse, we identified 3314 patients with pain receiving care at a large academic institution in New York City during a baseline period (September 23, 2019–March 22, 2020) and counted telephone, video, and in-person visits during the following conditions: a shutdown period (March 23, 2020–May 23, 2020), when nonessential in-person visits were strictly limited, and a reopening period (May 23, 2020–September 23, 2020), when restrictions were relaxed and in-person visits were available. Patients were categorized into 4 groups based on the technology used to complete a visit: (1) video, (2) telephone, (3) in-person, and (4) no visit. Results:. Patients who were older, publicly insured, and identified as Black or Hispanic were overrepresented in the telephone visit group during shutdown and the in-person group during reopening. A video visit during shutdown increased the likelihood of continued video visit use during reopening despite the return of in-person visits. Conclusions:. Results show differences in how patients with pain accessed clinical care in a socially distanced world and that flexibility in method of health care delivery may reduce barriers to access. Future research will identify factors (eg, Internet access, digital literacy, provider–patient relationships) driving heterogeneity in telehealth use in patients with pain.

Sickle cell disease (SCD) is a debilitating single gene disorder caused by a single point mutation that results in physical deformation (i.e. sickling) of erythrocytes at reduced oxygen tensions. Up to 75% of SCD in newborns world-wide occurs in sub-Saharan Africa, where neonatal and childhood mortality from sickle cell related complications is high. While SCD research across the globe is tackling the disease on multiple fronts, advances have yet to significantly impact on the health and quality of life of SCD patients, due to lack of coordination of these disparate efforts. Ensuring data across studies is directly comparable through standardization is a necessary step towards realizing this goal. Such a standardization requires the development and implementation of a disease-specific ontology for SCD that is applicable globally. Ontology development is best achieved by bringing together experts in the domain to contribute their knowledge. The SCD community and H3ABioNet members joined forces at a recent SCD Ontology workshop to develop an ontology covering aspects of SCD under the classes: phenotype, diagnostics, therapeutics, quality of life, disease modifiers and disease stage. The aim of the workshop was for participants to contribute their expertise to development of the structure and contents of the SCD ontology. Here we describe the proceedings of the Sickle Cell Disease Ontology Workshop held in Cape Town South Africa in February 2016 and its outcomes. The objective of the workshop was to bring together experts in SCD from around the world to contribute their expertise to the development of various aspects of the SCD ontology.

Abstract Timely and effective clinical decision-making for COVID-19 requires rapid identification of risk factors for disease outcomes. Our objective was to identify characteristics available immediately upon first clinical evaluation related COVID-19 mortality. We conducted a retrospective study of 8770 laboratory-confirmed cases of SARS-CoV-2 from a network of 53 facilities in New-York City. We analysed 3 classes of variables; demographic, clinical, and comorbid factors, in a two-tiered analysis that included traditional regression strategies and machine learning. COVID-19 mortality was 12.7%. Logistic regression identified older age (OR, 1.69 [95% CI 1.66–1.92]), male sex (OR, 1.57 [95% CI 1.30–1.90]), higher BMI (OR, 1.03 [95% CI 1.102–1.05]), higher heart rate (OR, 1.01 [95% CI 1.00–1.01]), higher respiratory rate (OR, 1.05 [95% CI 1.03–1.07]), lower oxygen saturation (OR, 0.94 [95% CI 0.93–0.96]), and chronic kidney disease (OR, 1.53 [95% CI 1.20–1.95]) were associated with COVID-19 mortality. Using gradient-boosting machine learning, these factors predicted COVID-19 related mortality (AUC = 0.86) following cross-validation in a training set. Immediate, objective and culturally generalizable measures accessible upon clinical presentation are effective predictors of COVID-19 outcome. These findings may inform rapid response strategies to optimize health care delivery in parts of the world who have not yet confronted this epidemic, as well as in those forecasting a possible second outbreak.

Abstract Introduction Music performance anxiety (MPA) is characterized by long-lasting, high intensity apprehension associated with performing music in public. At extreme levels, MPA can impair the career and quality of life. Our goal is to describe the clinical profile, perceived causes and coping strategies associated with MPA. Methods In this cross-sectional study, several self-assessment instruments were administered to a sample of 214 Brazilian musicians (68% male, 53.3% classical/46.7% popular musicians). Data were analyzed using descriptive and parametric statistics, based on the variables of musical training and level of MPA. Results Percentages of indicators of pathology were high (40% high MPA levels, 37% social anxiety, 12.5% depression, 13.5% alcohol abuse), and musicians with high MPA levels were the most affected. A wide variety of situations were associated with MPA, especially those related to the individual (pressure from self/concern about audience). Emotion-focused coping and internal resources were prominent among the resources used for coping with MPA (breathing, increased practice, familiarization with performance venue), although they were not always effective. It was relatively uncommon for musicians to seek specialized resources and treatments. Conclusions The results demonstrate the vulnerability of the targeted professional groups and the need for preventive strategies and behavioral, environmental, educational, and pharmacological interventions to change this scenario.

Several studies have revealed that the hyper-inflammatory response induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major cause of disease severity and death. However, predictive biomarkers of pathogenic inflammation to help guide targetable immune pathways are critically lacking. We implemented a rapid multiplex cytokine assay to measure serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-[alpha] and IL-1[beta] in hospitalized patients with coronavirus disease 2019 (COVID-19) upon admission to the Mount Sinai Health System in New York. Patients (n = 1,484) were followed up to 41 d after admission (median, 8 d), and clinical information, laboratory test results and patient outcomes were collected. We found that high serum IL-6, IL-8 and TNF-[alpha] levels at the time of hospitalization were strong and independent predictors of patient survival (P < 0.0001, P = 0.0205 and P = 0.0140, respectively). Notably, when adjusting for disease severity, common laboratory inflammation markers, hypoxia and other vitals, demographics, and a range of comorbidities, IL-6 and TNF-[alpha] serum levels remained independent and significant predictors of disease severity and death. These findings were validated in a second cohort of patients (n = 231). We propose that serum IL-6 and TNF-[alpha] levels should be considered in the management and treatment of patients with COVID-19 to stratify prospective clinical trials, guide resource allocation and inform therapeutic options. Elevated levels of serum IL-6 and TNF-[alpha] at the time of hospitalization are independent and significant predictors of clinical outcome in two cohorts of patients with COVID-19., Author(s): Diane Marie Del Valle [sup.1] [sup.2] [sup.3] , Seunghee Kim-Schulze [sup.1] [sup.2] [sup.3] [sup.4] , Hsin-Hui Huang [sup.5] [sup.6] [sup.7] , Noam D. Beckmann [sup.8] , Sharon Nirenberg [sup.8] [...]