Evidence-Based Cognitive Endoscopy Simulators: Do They Exist? A Systematic Search and Evaluation of Existing Platforms.

BACKGROUND: The development of guidelines by gastroenterology societies increasingly stresses evidence-based endoscopic practice. AIMS: We performed a systematic assessment to determine whether endoscopic video teaching platforms incorporate evidence-based educational strategies and methods in order to disseminate guideline-based endoscopic management strategies. METHODS: Platforms with a video component were systematically identified using the Google search engine, Apple and Android application stores, and searching four major gastroenterology society websites and three known platforms, to identify all relevant platforms. Two video samples from each teaching platform were reviewed independently by two authors and assessed for use of a priori defined principles of evidence-based medicine, as determined by consensus agreement and for the use of simulation. RESULTS: Fourteen platforms were included in the final analysis, and two videos from each were analyzed. One of the 14 platforms used simulation and incorporated evidence-based medicine principles consistently. Nine of the 14 platforms were not transparent in regard to citation. None of the platforms consistently cited the certainty of evidence or explained how evidence was selected. CONCLUSIONS: Education of guideline-based endoscopic management strategies using principles of evidence-based medicine is under-utilized in endoscopic videos. In addition, the use of cognitive simulation is absent in this arena. There is a paucity of evidence-based cognitive endoscopy simulators designed for fellows that incorporate systematic evaluation, and efforts should be made to create this platform.

Exploring the relationship between mobility and COVID- 19 infection rates for the second peak in the United States using phase-wise association.

Human mobility plays an important role in the dynamics of infectious disease spread. Evidence from the initial nationwide lockdowns for COVID- 19 indicates that restricting human mobility is an effective strategy to contain the spread. While a direct correlation was observed early on, it is not known how mobility impacted COVID- 19 infection growth rates once lockdowns are lifted, primarily due to modulation by other factors such as face masks, social distancing, and the non-linear patterns of both mobility and infection growth. This paper introduces a piece-wise approach to better explore the phase-wise association between state-level COVID- 19 incidence data and anonymized mobile phone data for various states in the United States. Prior literature analyzed the linear correlation between mobility and the number of cases during the early stages of the pandemic. However, it is important to capture the non-linear dynamics of case growth and mobility to be usable for both tracking and forecasting COVID- 19 infections, which is accomplished by the piece-wise approach. The associations between mobility and case growth rate varied widely for various phases of the epidemic curve when the stay-at-home orders were lifted. The mobility growth patterns had a strong positive association of 0.7 with the growth in the number of cases, with a lag of 5 to 7 weeks, for the fast-growth phase of the pandemic, for only 20 states that had a peak between July 1st and September 30, 2020. Overall though, mobility cannot be used to predict the rise in the number of cases after initial lockdowns have been lifted. Our analysis explores the gradual diminishing value of mobility associations in the later stage of the outbreak. Our analysis indicates that the relationship between mobility and the increase in the number of cases, once lockdowns have been lifted, is tenuous at best and there is no strong relationship between these signals. But we identify the remnants of the last associations in specific phases of the growth curve.

Examining the COVID-19 case growth rate due to visitor vs. local mobility in the United States using machine learning.

Travel patterns and mobility affect the spread of infectious diseases like COVID-19. However, we do not know to what extent local vs. visitor mobility affects the growth in the number of cases. This study evaluates the impact of state-level local vs. visitor mobility in understanding the growth with respect to the number of cases for COVID spread in the United States between March 1, 2020, and December 31, 2020. Two metrics, namely local and visitor transmission risk, were extracted from mobility data to capture the transmission potential of COVID-19 through mobility. A combination of the three factors: the current number of cases, local transmission risk, and the visitor transmission risk, are used to model the future number of cases using various machine learning models. The factors that contribute to better forecast performance are the ones that impact the number of cases. The statistical significance of the forecasts is also evaluated using the Diebold-Mariano test. Finally, the performance of models is compared for three waves across all 50 states. The results show that visitor mobility significantly impacts the case growth by improving the prediction accuracy by 33.78%. We also observe that the impact of visitor mobility is more pronounced during the first peak, i.e., March-June 2020.

A multimodal sensor dataset for continuous stress detection of nurses in a hospital.

Advances in wearable technologies provide the opportunity to monitor many physiological variables continuously. Stress detection has gained increased attention in recent years, mainly because early stress detection can help individuals better manage health to minimize the negative impacts of long-term stress exposure. This paper provides a unique stress detection dataset created in a natural working environment in a hospital. This dataset is a collection of biometric data of nurses during the COVID-19 outbreak. Studying stress in a work environment is complex due to many social, cultural, and psychological factors in dealing with stressful conditions. Therefore, we captured both the physiological data and associated context pertaining to the stress events. We monitored specific physiological variables such as electrodermal activity, Heart Rate, and skin temperature of the nurse subjects. A periodic smartphone-administered survey also captured the contributing factors for the detected stress events. A database containing the signals, stress events, and survey responses is publicly available on Dryad.

Association mining based approach to analyze COVID-19 response and case growth in the United States.

Containing the COVID-19 pandemic while balancing the economy has proven to be quite a challenge for the world. We still have limited understanding of which combination of policies have been most effective in flattening the curve; given the challenges of the dynamic and evolving nature of the pandemic, lack of quality data etc. This paper introduces a novel data mining-based approach to understand the effects of different non-pharmaceutical interventions in containing the COVID-19 infection rate. We used the association rule mining approach to perform descriptive data mining on publicly available data for 50 states in the United States to understand the similarity and differences among various policies and underlying conditions that led to transitions between different infection growth curve phases. We used a multi-peak logistic growth model to label the different phases of infection growth curve. The common trends in the data were analyzed with respect to lockdowns, face mask mandates, mobility, and infection growth. We observed that face mask mandates combined with mobility reduction through moderate stay-at-home orders were most effective in reducing the number of COVID-19 cases across various states.

Mapping of melanin-concentrating hormone receptor 1 B cell epitopes predicts two major binding sites for vitiligo patient autoantibodies.

The melanin-concentrating hormone receptor 1 (MCHR1) has been identified as a B cell autoantigen in vitiligo with antibodies to the receptor detectable in binding and function-blocking assays. Two epitope domains (amino acids 1-138 and 139-298) have been previously identified. In this study, we aimed to further define the epitope specificity of MCHR1 antibodies using phage-display technology and to identify the epitopes recognised by receptor antibodies detected in MCHR1 function-blocking assays. Antibody reactivity to MCHR1 peptides 51-80, 85-98, 154-158 and 254-260 was identified by phage-display and subsequently confirmed in phage ELISA in 2/12, 5/12, 3/12 and 6/12 of vitiligo patients, respectively. The results suggest that major autoantibody epitopes are localised in the 85-98 and 254-260 amino acid regions of MCHR1 with minor epitopes in amino acid sequences 51-80 and 154-158. Antibodies with MCHR1 function-blocking activity were determined to recognise epitope 254-260, this being the first epitope to be reported as a target site for antibodies that block the function of the receptor.

The melanin-concentrating hormone receptor 1, a novel target of autoantibody responses in vitiligo.

Vitiligo is a common depigmenting disorder resulting from the loss of melanocytes in the skin. The pathogenesis of the disease remains obscure, although autoimmune mechanisms are thought to be involved. Indeed, autoantibodies and autoreactive T lymphocytes that target melanocytes have been reported in some vitiligo patients. The objective of this study was to identify pigment cell antigens that are recognized by autoantibodies in vitiligo. Using IgG from vitiligo patients to screen a melanocyte cDNA phage-display library, we identified the melanin-concentrating hormone receptor 1 (MCHR1) as a novel autoantigen related to this disorder. Immunoreactivity against the receptor was demonstrated in vitiligo patient sera by using radiobinding assays. Among sera from healthy controls and from patients with autoimmune disease, none exhibited immunoreactivity to MCHR1, indicating a high disease specificity for Ab's against the receptor. Inhibition of MCH binding to its receptor by IgG from vitiligo patients was also shown.

Sedation in the Endoscopy Suite.

OPINION STATEMENT: Sedation practices in the endoscopy suite have changed dramatically in the decades since the introduction of routine colonoscopy and esophagogastroduodenoscopy (EGD). Patients initially received moderate sedation (or even no sedation), but now frequently receive monitored anesthesia care (MAC). This significant shift has introduced anesthesiologists to the endoscopy suite along with new sedative medications and safety concerns. Appreciating the ramifications of this change requires an understanding of sedation depth, patient selection, drug use, sedation delivery, patient monitoring, recovery from sedation, and patient outcomes. Furthermore, the changing landscape of healthcare quality and reimbursement challenges us to provide the best possible care for our patients in the most economical way possible. The endoscopy suite is a unique sedation environment, and it is the purpose of this article to review those elements that contribute to a uniquely demanding work environment.

Autoantibodies in vitiligo patients recognize multiple domains of the melanin-concentrating hormone receptor.

Previously, we reported the identification of autoantibodies against the melanin-concentrating hormone receptor 1 in patients with vitiligo. In this study, the B cell epitopes on melanin-concentrating hormone receptor 1 that are recognized by these autoantibodies have been identified. Deletion derivatives of melanin-concentrating hormone receptor 1 complementary DNA were constructed and then translated in vitro with the concomitant incorporation of [35S]-methionine into the protein products. The [35S]-labeled melanin-concentrating hormone receptor 1 derivatives were subsequently used in radio-binding assays to investigate the reactivity of sera from nine vitiligo patients that were known to contain antibodies to the receptor. Analysis of the results obtained in the radio-binding assays suggested the existence of multiple antibody binding sites on melanin-concentrating hormone receptor 1, including regions between amino acids 1 to 138 and 139 to 298. Several patients exhibited autoantibodies to more than one melanin-concentrating hormone receptor 1 epitope indicating a heterogeneous humoral response to the receptor. Computer prediction of the potential B cell epitopes on melanin-concentrating hormone receptor 1 revealed that the epitope domains identified overlapped, at least in part, with regions predicted to be highly antigenic.

Determination of Catechin and Epicatechin Content in Chocolates by High-Performance Liquid Chromatography.

A simple and sensitive reversed phase high-performance liquid chromatographic (HPLC) method has been developed for the determination of catechin and epicatechin in cocoa powder and chocolates. The separation was achieved on a reversed phase C 18 column (TARGA) 5 µm by gradient elution with a flow rate of 1.0 mL/minute with an operating temperature of 30°C and detection with a UV-Visible detector was at 280 nm. The method was validated for linearity, precision, intra- and interday precision, and accuracy. The developed method is successfully applied for the determination of catechin and epicatechin content in chocolates. The Godiva brand chocolate contains high concentration of epicatechin.

Myocardial infarction triggers chronic cardiac autoimmunity in type 1 diabetes.

Patients with type 1 diabetes (T1D) suffer excessive morbidity and mortality after myocardial infarction (MI) that is not fully explained by the metabolic effects of diabetes. Acute MI is known to trigger a profound innate inflammatory response with influx of mononuclear cells and production of proinflammatory cytokines that are crucial for cardiac repair. We hypothesized that these same pathways might exert "adjuvant effects" and induce pathological responses in autoimmune-prone T1D hosts. Here, we show that experimental MI in nonobese diabetic mice, but not in control C57BL/6 mice, results in a severe post-infarction autoimmune (PIA) syndrome characterized by destructive lymphocytic infiltrates in the myocardium, infarct expansion, sustained cardiac autoantibody production, and T helper type 1 effector cell responses against cardiac (α-)myosin. PIA was prevented by inducing tolerance to α-myosin, demonstrating that immune responses to cardiac myosin are essential for this disease process. Extending these findings to humans, we developed a panel of immunoassays for cardiac autoantibody detection and found autoantibody positivity in 83% post-MI T1D patients. We further identified shared cardiac myosin autoantibody signatures between post-MI T1D patients and nondiabetic patients with myocarditis, which were absent in post-MI type 2 diabetic patients, and confirmed the presence of myocarditis in T1D by cardiac magnetic resonance imaging techniques. These data provide experimental and clinical evidence for a distinct post-MI autoimmune syndrome in T1D. Our findings suggest that PIA may contribute to worsened post-MI outcomes in T1D and highlight a role for antigen-specific immunointervention to selectively block this pathway.

Myocardial parvovirus B19 persistence: lack of association with clinicopathologic phenotype in adults with heart failure.

BACKGROUND: Multiple viruses have been isolated from the heart, but their significance remains controversial. We sought to determine the prevalence of cardiotropic viruses in endomyocardial biopsy (EMB) samples from adult patients with heart failure (HF) and to define the clinicopathologic profile of patients exhibiting viral positivity. METHODS AND RESULTS: EMB from 100 patients (median ejection fraction, 30%; interquartile range [IQR], 20% to 45%) presenting for cardiomyopathy evaluation (median symptom duration, 5 months; IQR, 1 to 13 months) were analyzed by polymerase chain reaction for adenovirus, cytomegalovirus, enteroviruses, Epstein-Barr virus, and parvovirus B19. Each isolate was sequenced, and viral load was determined. Parvovirus B19 was the only virus detected in EMB samples (12% of subjects). No patient had antiparvovirus IgM antibodies, but all had IgG antibodies, suggesting viral persistence. The clinical presentation of parvovirus-positive patients was markedly heterogeneous with both acute and chronic HF, variable ventricular function, and ischemic cardiomyopathy. No patient met Dallas histopathologic criteria for active or borderline myocarditis. Two patients with a positive cardiac MRI and presumed "parvomyocarditis" had similar viral loads to autopsy controls without heart disease. The oldest parvovirus-positive patients were positive for genotype 2, suggesting lifelong persistence in the myocardium. CONCLUSIONS: Parvovirus B19 was the only virus isolated from EMB samples in this series of adult patients with HF from the United States. Positivity was associated with a wide array of clinical presentations and HF phenotypes. Our studies do not support a causative role for parvovirus B19 persistence in HF and, therefore, advocate against the use of antiviral therapy for these patients.

Impaired thymic tolerance to α-myosin directs autoimmunity to the heart in mice and humans.

Autoimmunity has long been linked to myocarditis and its sequela, dilated cardiomyopathy, the leading causes of heart failure in young patients. However, the underlying mechanisms are poorly defined, with most clinical investigations focused on humoral autoimmunity as the target for intervention. Here, we show that the α-isoform of myosin heavy chain (α-MyHC, which is encoded by the gene Myh6) is the pathogenic autoantigen for CD4+ T cells in a spontaneous mouse model of myocarditis. Further, we found that Myh6 transcripts were absent in mouse medullary thymic epithelial cells (mTECs) and peripheral lymphoid stromal cells, which have been implicated in mediating central and peripheral T cell tolerance, respectively. Transgenic expression of α-MyHC in thymic epithelium conferred tolerance to cardiac myosin and prevented myocarditis, demonstrating that α-MyHC is a primary autoantigen in this disease process. Remarkably, we found that humans also lacked α-MyHC in mTECs and had high frequencies of α-MyHC-specific T cells in peripheral blood, with markedly augmented T cell responses to α-MyHC in patients with myocarditis. Since α-MyHC constitutes a small fraction of MyHC in human heart, these findings challenge the longstanding notion that autoimmune targeting of MyHC is due to its cardiac abundance and instead suggest that it is targeted as a result of impaired T cell tolerance mechanisms. These results thus support a role for T cell-specific therapies for myocarditis.

Louisiana: a model for advancing regional e-Research through cyberinfrastructure.

Louisiana researchers and universities are leading a concentrated, collaborative effort to advance statewide e-Research through a new cyberinfrastructure: computing systems, data storage systems, advanced instruments and data repositories, visualization environments and people, all linked together by software programs and high-performance networks. This effort has led to a set of interlinked projects that have started making a significant difference in the state, and has created an environment that encourages increased collaboration, leading to new e-Research. This paper describes the overall effort, the new projects and environment and the results to date.

Function-blocking autoantibodies to the melanin-concentrating hormone receptor in vitiligo patients.

Vitiligo is a common depigmenting skin disorder resulting from the loss of melanocytes in the cutaneous epidermis. Although the cause of the disease remains obscure, autoimmune mechanisms are thought to be involved. Recently, melanin-concentrating hormone receptor (MCHR)-binding autoantibodies have been identified in vitiligo patients. In the present study, we aimed to determine if MCHR autoantibodies could also affect receptor function either by direct activation or by blocking its response to melanin-concentrating hormone. The results indicated that 10/18 (56%) vitiligo patient IgG samples inhibited the function of MCHR expressed in a Chinese hamster ovary cell line. In contrast, neither control (n=20) nor SLE patient (n=10) IgG samples blocked receptor function. Compared with healthy controls, MCHR function-blocking autoantibodies were found at a significantly increased frequency in the vitiligo patient group (P=0.0004). No MCHR-activating autoantibodies were detected in any of the vitiligo patient, SLE patient or control IgG samples that were analysed. In addition, vitiligo patient IgGs were tested for MCHR autoantibodies that could mediate antibody-dependent cell-mediated cytotoxicity via the receptor. However, this could only be demonstrated in two vitiligo patient sera. Overall, this work has provided additional evidence that MCHR is a B-cell autoantigen in vitiligo and has demonstrated the existence of MCHR function-blocking autoantibodies further to the receptor-binding autoantibodies previously reported.