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BACKGROUND & AIMS Vedolizumab (VDZ) is a monoclonal antibody directed against α4β7 integrin heterodimer, approved for patients with inflammatory bowel diseases (IBD). This study aimed at identifying immunological variables associated with response to vedolizumab in patients with ulcerative colitis (UC) and Crohn's disease (CD). METHODS This is a phase-IV explorative prospective interventional trial. IBD patients received open-label VDZ at weeks 0, 2, 6 and 14. Patients with a clinical response at week 14 were maintained with VDZ up to week 54. At week 0 and 14 their peripheral blood was obtained and endoscopy with biopsies was performed. The week-14 clinical response and remission, week-54 clinical remission, and week-14 endoscopic response were evaluated as endpoints of the study. The expression of surface markers, chemokine receptors and α4β7 heterodimer on peripheral blood and lamina propria lymphocytes was assessed by flow cytometry. A panel of soluble mediators were assessed in sera at baseline and at weions, please email journals.permissions@oup.com.OBJECTIVE The detection of gene fusion events is important for the diagnosis and management of malignancies. In this study, we describe the validation of a next-generation sequencing assay for multiplex detection of gene fusions. METHODS Based on previously described gene fusion events that occur in pediatric oncology, a custom anchored multiplex next-generation sequencing assay was designed to target 93 genes. RESULTS A total of 24 previously characterized specimens were examined. Twenty specimens had 1 or more previously described fusion events, and 4 specimens were negative for fusion events. The accuracy across specimens was 100% (20 of 20 specimens). The analytical sensitivity and specificity were both 100%. Interday reproducibility for fusion events was 94%; in comparison, intraday reproducibility was 90%. CONCLUSION This multiple-gene fusion assay demonstrated appropriate sensitivity, specificity, and accuracy for clinical use. We anticipate that this assay will improve the diagnosis and management of patients with pediatric solid tumors. © American Society for Clinical Pathology, 2020. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and antisignal recognition particle (SRP) antibodies are frequently associated with immune-mediated necrotizing myopathy (IMNM). However, the difference in clinical manifestations between anti-HMGCR and anti-SRP antibodies is unclear. HMGCR is an essential enzyme for cholesterol biosynthesis and is inhibited by statins that regulate apoptosis of Bcl-2-positive and beta chemokine receptor 4 (CCR4)-positive lymphoma cells. In this study, we aimed to clarify Bcl-2 and CCR4 expressions of lymphocytes in anti-HMGCR antibody-positive IMNM and explore the difference between anti-HMGCR antibody-positive myopathy and other inflammatory myopathies. We retrospectively examined Bcl-2- and CCR4-positive lymphocyte infiltrations in muscle and skin biopsy specimens from 19 anti-HMGCR antibody-positive patients and 75 other idiopathic inflammatory myopathies (IIMs) patients. A higher incidence of Bcl-2- and CCR4-positive lymphocytes was detected in the muscle and skin of anti-HMGCR antibody-positive IMNM patients (p  less then  0.001). In 5 patients with anti-HMGCR antibodies, Bcl-2-positive lymphocytes formed lymphocytic accumulations, which were not observed in other IIMs. Low-density lipoprotein cholesterol levels were not increased except for patients with Bcl-2-positive lymphocytic accumulations (p = 0.010). Bcl-2 and CCR4 lymphocyte infiltrations could be a pathological characteristic of anti-HMGCR antibody-positive IMNM. © 2020 American Association of Neuropathologists, Inc.This study aimed to develop and evaluate an improved median filter (IMF) with an adaptive mask size for light microscope (LM) images. We acquired images of the mouse first molar using a LM at 100× magnification. The images obtained using our proposed IMF were compared with those from a conventional median filter. Several parameters such as the contrast-to-noise ratio, coefficient of variation, no-reference assessments and peak signal-to-noise ratio were employed to evaluate the image quality quantitatively. The results demonstrated that the proposed IMF could effectively de-noise the LM images and preserve the image details, achieving a better performance than the conventional median filter. © The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Society of Microscopy. All rights reserved.For permissions, please e-mail journals.permissions@oup.com.The biomedical research and healthcare delivery communities have increasingly come to focus their attention on the role of data and computation in order to improve the quality, safety, costs, and outcomes of both wellness promotion and care delivery. Depending on the scale of such efforts, and the environments in which they are situated, they are referred to variably as personalized or precision medicine, population health, clinical transformation, value-driven care, or value-based transformation. Despite the original intent of many efforts and publications that have sought to define personalized, precision, or data-driven approaches to improving health and wellness, the use of such terminology in current practice often treats said activities as discrete areas of endeavor within minimal cross-linkage across or between scales of inquiry. We believe that this current state creates numerous barriers that are preventing the advancement of relevant science, practice, and policy. As such, we believe that it is necessary to amplify and reaffirm our collective understanding that these fields share common means of inquiry, differentiated only by the units of measure being utilized, their sources of data, and the manner in which they are executed. Therefore, in this perspective, we explore and focus attention on such commonalities and then present a conceptual framework that links constituent activities into an integrated model that we refer to as a precision healthcare system. The presentation of this framework is intended to provide the basis for the types of shared, broad-based, and descriptive language needed to reference and realize such a framework. © The Author(s) 2020. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email journals.permissions@oup.com.Sir Alexander Morison's Physiognomy of Mental Diseases (1838) was created as a didactic tool for physicians, depicting lunatics in both the active and dormant states of disease. Through the act of juxtaposition, Morison constituted his subjects as their own Jekylls and Hydes, capable of radical transformation. In doing so, he marshaled artistic and clinical, visual and textual approaches in order to pose a particular argument about madness as a temporally manifested, visually distinguishable state defined by its contrast with reason. This argument served a crucial function in legitimizing the emergent discipline of psychiatry by applying biomedical methodologies to the observation and classification of distinctly physical symptoms. Robert Louis Stevenson's "quintessentially Victorian parable" serves as a metaphor for the way 19th-century alienists conceptualized insanity, while the theme of duality at the core of Stevenson's story serves as a framework for conceptualizing both psychiatry and the subjects it generates. It was (and is) a discipline formulated around narrative as the primary organizing structure for its particular set of paradoxes, and specifically, narratives of the self as a fluid, dynamic, and contradictory entity. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.A simple, rapid, cost-effective and green analytical method is developed based on ultrasound-assisted dispersive liquid-liquid microextraction (US-DLLME) coupled to thin-layer chromatography (TLC)-image analysis for the simultaneous determination of two major alkaloids of Strychnos nux-vomica L i.e., strychnine and brucine. The method is composed of three steps, namely (i) US-DLLME by injecting a mixture of 100-μL chloroform (extraction solvent) and 1-mL methanol (disperser solvent) in 5 mL of aqueous sample, followed by ultrasonication and centrifugation, (ii) TLC of 20 μL of sedimented phase with methanol ammonia (1001.5, v/v) as the mobile phase and visualization under ultraviolet radiation (254 nm) and (iii) photography of TLC plate and quantification of spots by image analysis using freely available imageJ software (National Institute of Health, Bethesda, MD, USA). The limit of detection and limit of quantification for both alkaloids were found to be in the range of 0.12-0.15 and 0.36-0.48 μg/spot, respectively. The method was found to be linear in the range of 0.5-5 μg/spot with correlation coefficient (R2) of 0.995 and 0.997 for strychnine and brucine, respectively. The developed method was successfully applied for the determination of strychnine and brucine in Ayurvedic formulations and blood samples. The method does not require any sophisticated instrument and handling skills and can be adopted for rapid analysis of strychnine and brucine in forensic toxicological laboratories. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email journals.permissions@oup.com.BACKGROUND Studies among individuals ages ≥65 years have found a moderately higher relative vaccine effectiveness (RVE) for the high-dose (HD) influenza vaccine compared to standard-dose (SD) products for most seasons. Studies during the A(H3N2)-dominated 2017-18 season showed slightly higher RVE for the cell-cultured vaccine compared to SD egg-based vaccines. We investigated the RVE of influenza vaccines among Medicare beneficiaries ages ≥65 years during the 2018-19 season. METHODS Retrospective cohort study using inverse probability of treatment weighting and Poisson regression to evaluate RVE in preventing influenza hospital encounters. RESULTS Among 12,777,214 beneficiaries, the egg-based adjuvanted (RVE 7.7%, 95% CI 3.9 to 11.4%) and high-dose (RVE 4.9%, 95% CI 1.7 to 8.1%) vaccines were marginally more effective than the egg-based quadrivalent vaccines. The cell-cultured quadrivalent vaccines were not significantly more effective than the egg-based quadrivalent vaccines (RVE 2.5%, 95% CI -2.4 to 7.3%). CONCLUSIONS We did not find major effectiveness differences between licensed vaccines used among the elderly during the 2018-19 season. Consistent with prior research, we found that the egg-based adjuvanted and high-dose vaccines were slightly more effective than the egg-based quadrivalent vaccines. Published by Oxford University Press for the Infectious Diseases Society of America 2020. This work is written by (a) US Government employee(s) and is in the public domain in the US.BACKGROUND Lay diagnosis is a widely used diagnostic approach for home management of common illnesses in Nigeria. This study aimed to explore the perspectives of caregivers and healthcare professionals on lay diagnosis of childhood malaria and pneumonia. Aligned to this, the study sought to explore the feasibility of training caregivers in the Integrated Management of Childhood Illness (IMCI) guidelines for improved recognition and treatment of these diseases. METHODS A qualitative study using individual face-to-face semi-structured interviews was conducted in Benin City, Nigeria. Participants included 13 caregivers with children under 5 years and 17 healthcare professionals (HPs). An inductive approach to thematic analysis was used to generate themes and analyses. see more RESULTS Caregivers relied on lay diagnosis but recognised its limitations. The perceived severity of malaria and pneumonia significantly influenced caregivers' preference for reliance on lay diagnosis practices, health-seeking behaviour and willingness to undertake training in IMCI guidelines for home management of diseases.