Johnstonherman9004

CONTEXT.— Clinical next-generation sequencing (NGS) is being rapidly adopted, but analysis and interpretation of large data sets prompt new challenges for a clinical lab setting. Selleck C16 Clinical NGS results rely heavily on the bioinformatics pipeline for identifying genetic variation in complex samples. The choice of bioinformatics algorithms, genome assembly, and genetic annotation databases are important for determining genetic alterations associated with disease. The analysis methods are often tuned to the assay to maximize accuracy. Once a pipeline has been developed, it must be validated to determine accuracy and reproducibility for samples similar to real-world cases. In silico proficiency testing or institutional data exchange will ensure consistency among clinical laboratories. OBJECTIVE.— To provide molecular pathologists a step-by-step guide to bioinformatics analysis and validation design in order to navigate the regulatory and validation standards of implementing a bioinformatic pipelines as a part of a new clinical NGS assay. DATA SOURCES.— This guide uses published studies on genomic analysis, bioinformatics methods, and methods comparison studies to inform the reader on what resources, including open source software tools and databases, are available for genetic variant detection and interpretation. CONCLUSIONS.— This review covers 4 key concepts (1) bioinformatic analysis design for detecting genetic variation, (2) the resources for assessing genetic effects, (3) analysis validation assessment experiments and data sets, including a diverse set of samples to mimic real-world challenges that assess accuracy and reproducibility, and (4) if concordance between clinical laboratories will be improved by proficiency testing designed to test bioinformatic pipelines.CONTEXT.— An increasing number of molecular laboratories are implementing next-generation sequencing platforms to identify clinically actionable and relevant genomic alterations for precision oncology. OBJECTIVE.— To describe the validation studies as per New York State-Department of Health (NYS-DOH) guidelines for the Oncomine Comprehensive Panel v2, which was originally tailored to the National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) trial. DESIGN.— Accuracy, precision, and reproducibility were investigated by using 130 DNA and 18 RNA samples from cytology cell blocks; formalin-fixed, paraffin-embedded tissues; and frozen samples. Analytic sensitivity and specificity were tested by using ATCC and HapMap cell lines. RESULTS.— High accuracy and precision/reproducibility were observed for single nucleotide variants and insertion/deletions. We also share our experience in the detection of gene fusions and copy number alterations from an amplicon-based sequencing platform. After sequencing analysis, variant annotation and report generation were performed by using the institutional knowledgebase. CONCLUSIONS.— This study serves as an example for validating a comprehensive targeted next-generation sequencing assay with both DNASeq and RNASeq components for NYS-DOH.OBJECTIVE Myoelectric activity of neck extensor muscles and head kinematic variables, when using a smartphone for one-handed browsing and two-handed texting while sitting, standing, and walking, were evaluated to compare the neck muscular load during these tasks and across the posture conditions. BACKGROUND There has been limited research on the relation between head-down postures and the muscular load on the neck of smartphone users. METHODS Twenty-one asymptomatic young users were asked to perform one-handed browsing and two-handed texting tasks in each of the posture conditions, and the myoelectric activities of the neck extensor muscles, head kinematic variables, and upper back posture were quantified. RESULTS The muscle activation level when using a phone during walking was 21.2% and 41.7% higher than that of sitting and standing on average (p less then .01). Head vertical and angular accelerations were also significantly greater (p less then .01) for walking than for sitting and standing conditions. Between the two conducted tasks, participants flexed their heads more significantly (p less then .01) with higher activation of the neck extensor muscles (p less then .01) when texting as compared to when browsing. CONCLUSION Results indicate that two-handed texting while walking would be the most physically demanding scenario for neck musculature, and it might be attributable to the dynamics of the head while walking with the head facing downwards. APPLICATION These findings can be used to better understand the potential relation between smartphone use and the occurrence of neck musculoskeletal problems and to inform the users of the ergonomic risks of using smartphones while walking.Background Real-life data often highlight the side effects of certain drugs not previously reported in randomized controlled trials (RCTs).Objective To describe cutaneous inflammatory eruptions in psoriatic patients treated with an anti IL-17A agent (secukinumab or ixekizumab).Methods Retrospective analysis of a cohort of patients with chronic plaque psoriasis who started an anti IL-17A agent between September 2016-February 2019 and who developed cutaneous inflammatory eruptions during treatment. A systematic review of similar events reported in the literature was performed.Results Data of 468 patients were reviewed and 27 cutaneous inflammatory eruptions of 27 (5.8%) patients were collected. The eruptions appeared after a mean of 16.9 ± 17.0 weeks of therapy showing a classical acute eczema in 11 patients (40.7%), an atopic dermatitis-like rash in 11 patients (40.7%) and a psoriasiform eruption in 5 patients (18.5%). Histopathology of 12/27 cases showed epidermal spongiosis in all these variants.Conclusion We described the clinic-pathologic features of some eczematous eruptions occurring in psoriatic patients, 3-4 months after treatment initiation with an anti IL-17A agent. Further investigations are needed to explain this phenomenon, that might be defined a paradoxical adverse event, based upon the role of IL17 in eczema pathogenesis.Purpose The aim of the study was to assess the amplitude of accommodation (AA) in patients with type 1 diabetes mellitus (DM) and without diabetic retinopathy.Materials and Methods In two age- and sex-matched groups - one with twenty-nine eyes of 29 patients with type 1 DM, the other with twenty-nine eyes of 29 healthy individuals - retinal nerve fibre layer thickness and macular volume were determined by using optic coherence tomography in all quadrants, whereas AA was measured with the minus lens technique. The mean values of all three measurements were compared between the groups, and the effect of age, disease duration, (HbA1c and fasting blood glucose on AA were analysed using multiple regression analysis.Results On average, participants were 25.0 ± 3.3 years old (range 19-30) in both groups (P = 1.000), and patients had type 1 DM for an average of 13.0 ± 3.3 years. Mean AA in the right eye was 7.3 ± 1.1 D among patients and 8.1 ± 1.1 D among controls (P = .005), as well as significantly negatively correlated with age in both groups (r = -0.735, P less then .001 and r = -0.819, P less then .001, respectively) and disease duration among patients (r = -0.434, P = .019). link2 In multivariable regression, age and disease duration significantly affected AA in patients, with an R2 value of 0.623 (P less then .001 and P = .025, respectively). Average RNFL thickness was significantly different between the groups (P = .014). Mean macular volumes for areas 1, 3 or 5 mm in diameter were similar between the groups.Conclusions AA was significantly lower among patients with type 1 DM than among healthy individuals, which suggests that the former might experience presbyopia earlier in life than the general population.Head and neck squamous cell carcinoma (HNSCC) is the sixth malignancy, which is characterized by poor prognosis or high mortality because of the lack of predicting markers. Aberrant cancer pseudogenes have been found predictive for prognosis. We aim to identify a pseudogene-based prognosis signature for HNSCC by machine learning. RNA-seq data were downloaded from The Cancer Genome Atlas, and 700 differentially-expressed pseudogenes were identified. The survival-related pseudogenes were screened through COX-regression analysis, which includes univariate regression, least absolute shrinkage and selection operator regression, and multivariate regression, and a five-pseudogene signature was constructed. The value of prediction for the signature was validated in multiple subgroups in terms of survival. Gene set enrichment analysis (GSEA) and coexpression analysis were used to determine the underlying biological functions. Seven hundred dysregulated pseudogenes were identified, and the five-pseudogene signature can distinguish the low-risk and high-risk patients for both training and testing sets and predicted prognosis with high sensitivity and specificity. Furthermore, the signature was applicable to patients of different genders, ages, stages, and grades. Coexpression analysis revealed that the five-pseudogene is associated with immune system. GSEA showed cancer-related biological process and pathways the five-pseudogene involved in. The five-pseudogene signature is not only a novel marker for prognosis but also a promising signature for monitoring therapeutic schedule. Therefore, our findings may have potential clinical significance.INTRODUCTION Interleaved neuromuscular electrical stimulation (iNMES) involves alternating stimulus pulses between the tibialis anterior muscle and common peroneal nerve. PURPOSE The current investigation aimed to characterize the relationship between contraction amplitude, motor unit (MU) "overlap" and contraction fatigability during iNMES. It was hypothesized that as iNMES generates progressively larger contractions, more MUs would be recruited from both sites (i.e. link3 more MU overlap), resulting in more fatigability for larger than smaller contractions. METHODS Fourteen participants completed 3 sessions. Fatigability was assessed as the decline in torque over 180 contractions (0.3s "on", 0.7s "off") when iNMES was delivered to produce initial contractions of ~5, 15, or 30 percent of a maximal voluntary contraction. RESULTS Although MU overlap increased significantly with contraction amplitude, the relative (percent) decline in torque was not different between the contraction amplitudes and torque declined on average by 23%. Contraction fatigability was not significantly correlated with either MU overlap or initial contraction amplitude. CONCLUSION iNMES can produce fatigue-resistant contractions across a functionally-meaningful range of contraction amplitudes for rehabilitation. NOVELTY BULLETS • Interleaved neuromuscular electrical stimulation progressively recruits motor units (MU) as contraction amplitude increases • However, the relative amount of fatigability of recruited MUs was not different as contraction amplitude increased • This suggests iNMES can be used effectively to produce fatigue-resistant and functionally-meaningful contractions.