Counting the mitotic cells in histopathological cancerous tissue areas is the most relevant indicator of tumor grade in aggressive breast cancer diagnosis. In this paper, we propose a robust and accurate technique for the automatic detection of mitoses from histological breast cancer slides using the multi-task deep learning framework for object detection and instance segmentation Mask RCNN. Our mitosis detection and instance segmentation framework is deployed for two main tasks it is used as a detection network to perform mitosis localization and classification in the fully annotated mitosis datasets (i.e., the pixel-level annotated datasets), and it is used as a segmentation network to estimate the mitosis mask labels for the weakly annotated mitosis datasets (i.e., the datasets with centroid-pixel labels only). https://www.selleckchem.com/products/cbl0137-cbl-0137.html We evaluate our approach on the fully annotated 2012 ICPR grand challenge dataset and the weakly annotated 2014 ICPR MITOS-ATYPIA challenge dataset. Our evaluation experiments show that we can obtaittps//github.com/MeriemSebai/MaskMitosis. Graphical Abstract Overview of MaskMitosis framework.Background/objective Multivariable prognostic scores play an important role for clinical decision-making, information giving to patients/relatives, benchmarking and guiding clinical trial design. Coagulopathy has been implicated on trauma and critical care outcomes, but few studies have evaluated its role on traumatic brain injury (TBI) outcomes. Our objective was to verify the incremental prognostic value of routine coagulopathy parameters in addition to the CRASH-CT score to predict 14-day mortality in TBI patients. Methods This is a prospective cohort of consecutive TBI patients admitted to a tertiary university hospital Trauma intensive care unit (ICU) from March/2012 to January/2015. The prognostic performance of the coagulation parameters platelet count, prothrombin time (international normalized ratio, INR) and activated partial thromboplastin time (aPTT) ratio was assessed through logistic regression adjusted for the original CRASH-CT score. A new model, CRASH-CT-Coag, was created and its calibration (Brier scores and Hosmer-Lemeshow (H-L) test), discrimination [area under the receiver operating characteristic curve (AUC-ROC) and the integrated discrimination improvement (IDI)] and clinical utility (net reclassification index) were compared to the original CRASH-CT score. Results A total 517 patients were included (median age 39 years, 85.1% male, median admission glasgow coma scale 8, neurosurgery on 44.9%). The 14-day mortality observed and predicted by the original CRASH-CT was 22.8% and 26.2%, respectively. Platelet count 30%) risk of death, the CRASH-CT-Coag model yielded a global net correct reclassification of 22.9% (95% CI 3.8-43.4%). Conclusions The addition of early markers of coagulopathy-platelet count, INR and aPTT ratio-to the CRASH-CT score increased its accuracy. Additional studies are required to externally validate this finding and further investigate the coagulopathy role on TBI outcomes.The UK adopted the opt-out system (deemed or presumed consent) in end-of-life organ donation enforceable in May 2020. Presumed consent applies to adults but not children. Transplant advocates have recommended that all children on end-of-life care should be referred for potential organ donation to increase the supply of transplantable organs in the UK. To buttress this objective, a UK survey of parents of deceased children mostly with neurologic disorders secondary to severe brain injuries recommended the integration of routine parental discussion of donation regardless of donation eligibility in end-of-life care. Donation discussions emphasize the utility and suitability of organs in dying children for transplantation to maximize consent rate. To ensure that this recommendation does not harm children and parents, contemporary medical, legal, cultural, and religious challenges to end-of-life organ donation should be disclosed in parental discussion of donation and resolved appropriately. To that effect, it is urged that (1) practice guidelines for the diagnosis and treatment of neurologic disorders secondary to severe brain injuries in children are updated and aligned with recent advances in neuroscience to eliminate potential errors from premature treatment discontinuation and/or incorrect diagnosis of death by brain(stem) criteria, (2) transparent and non-biased disclosure of all empiric information when discussing donation to ensure informed parental decision-making, and (3) a societal dialogue is conducted on the legal, cultural, and religious consequences of integration of routine donation discussion and referral in end-of-life care of children in the UK.Therapeutic plasma exchange (TPE) is an extracorporeal process in which a large volume of whole blood is taken from the patient's vein. Plasma is then separated from the other cellular components of the blood and discarded while the remaining blood components may then be returned to the patient. Replacement fluids such as albumin or fresh-frozen plasma may or may not be used. TPE has been used clinically for the removal of pathologic targets in the plasma in a variety of conditions, such as pathogenic antibodies in autoimmune disorders. TPE is becoming more common in the neurointensive care space as autoimmunity has been shown to play an etiological role in many acute neurological disorders. It is important to note that not only does TPE removes pathologic elements from the plasma, but may also remove drugs, which may be an intended or unintended consequence. The objective of the current review is to provide an up-to-date summary of the available evidence pertaining to drug removal via TPE and provide relevant clinical suggestions where applicable. This review also aims to provide an easy-to-follow clinical tool in order to determine the possibility of a drug removal via TPE given the procedure-specific and pharmacokinetic drug properties.Background As the COVID-19 pandemic developed, reports of neurological dysfunctions spanning the central and peripheral nervous systems have emerged. The spectrum of acute neurological dysfunctions may implicate direct viral invasion, para-infectious complications, neurological manifestations of systemic diseases, or co-incident neurological dysfunction in the context of high SARS-CoV-2 prevalence. link2 A rapid and pragmatic approach to understanding the prevalence, phenotypes, pathophysiology and prognostic implications of COVID-19 neurological syndromes is urgently needed. Methods The Global Consortium to Study Neurological dysfunction in COVID-19 (GCS-NeuroCOVID), endorsed by the Neurocritical Care Society (NCS), was rapidly established to address this need in a tiered approach. Tier-1 consists of focused, pragmatic, low-cost, observational common data element (CDE) collection, which can be launched immediately at many sites in the first phase of this pandemic and is designed for expedited ethical board review ates of each neurological finding divided by the average census of COVID-19 positive patients over the study period. Secondary outcomes include in-hospital, 30 and 90-day morality, discharge modified Rankin score, ventilator-free survival, ventilator days, discharge disposition, and hospital length of stay. Results In a one-month period (3/27/20-4/27/20) the GCS-NeuroCOVID consortium was able to recruit 71 adult study sites, representing 17 countries and 5 continents and 34 pediatrics study sites. Conclusions This is one of the first large-scale global research collaboratives urgently assembled to evaluate acute neurological events in the context of a pandemic. The innovative and pragmatic tiered study approach has allowed for rapid recruitment and activation of numerous sites across the world-an approach essential to capture real-time critical neurological data to inform treatment strategies in this pandemic crisis.Despite the pervasive nature of various forms of impairment associated with attention-deficit/hyperactivity disorder (ADHD), the precise nature of their associations with ADHD and related sluggish cognitive tempo (SCT), particularly at the heterogeneous item level, remains ambiguous. Using innovative network analysis techniques, we sought to identify and examine the concurrent validity of ADHD and SCT bridge items (i.e., those demonstrating the most robust relations with various forms of impairment) with respect to Overall, Home-School, and Community-Leisure impairment domains. Parents of a nationally representative sample of 1742 children (50.17% male) aged 6-17 years completed rating scales of ADHD, SCT, and impairment. Assessment of Bridge Expected Influence suggested eight bridge items primarily from impulsive and Task Completion (i.e., overlapping SCT and inattentive) domains that demonstrated relations with impairment in school performance, completing chores at home, interacting with family members, following rules, and playing sports. Sum scores only including bridge items exhibited relations with Overall, Home-School, and Community-Leisure impairment domains comparable to that of sum scores including all items. Bridge impairment areas were generally consistent across "Childhood" (6-11 years) and "Adolescence" (12-17 years). Problems listening and slowness emerged as bridge items in Childhood, whereas difficulties following through on instructions, problems waiting one's turn, and social withdrawal emerged in Adolescence. Given the comparable validity of ADHD- and SCT-related bridge items versus all items, bridge items, together, may be the most efficient indicators of impairment. Further clarification is needed across development to inform personalized assessment and intervention protocols that account for item-level heterogeneity in ADHD, SCT, and impairment phenotypes.Heightened reward sensitivity has been proposed as a risk factor for developing behavioral disorders whereas heightened punishment sensitivity has been related to the development of anxiety disorders in youth. Combining a cross-sectional (n = 696, mean age = 16.14) and prospective (n = 598, mean age = 20.20) approach, this study tested the hypotheses that an attentional bias for punishing cues is involved in the development of anxiety disorders and an attentional bias for rewarding cues in the development of behavioral disorders. A spatial orientation task was used to examine the relation between an attentional bias for punishing cues and an attentional bias for rewarding cues with anxiety and behavioral problems in a subsample of a large prospective population cohort study. Our study indicates that attentional biases to general cues of punishment and reward do not seem to be important risk factors for the development of anxiety or behavioral problems respectively. It might be that attentional biases play a role in the maintenance of psychological problems. link3 This remains open for future research.Scleroderma (systemic sclerosis; SSc) is a complex and highly heterogeneous multisystem rheumatic disease characterized by vascular abnormality, immunologic derangement, and excessive deposition of extracellular matrix (ECM) proteins. To date, the etiology of this life-threatening disorder remains not fully clear. More and more studies show epigenetic modifications play a vital role. The aberrant epigenetic status of certain molecules such as Fli-1, BMPRII, NRP1, CD70, CD40L, CD11A, FOXP3, KLF5, DKK1, SFRP1, and so on contributes to the pathogenesis of progressive vasculopathy, autoimmune dysfunction, and tissue fibrosis in SSc. Meanwhile, numerous miRNAs including miR-21, miR-29a, miR-196a, miR-202-3p, miR-150, miR-let-7a, and others are involved in the process. In addition, the abnormal epigenetic biomarker levels of CD11a, Foxp3, HDAC2, miR-30b, miR-142-3p, miR-150, miR-5196 in SSc are closely correlated with disease severity. In this chapter, we not only review new advancements on the epigenetic mechanisms involved in the pathogenesis of SSc and potential epigenetic biomarkers, but also discuss the therapeutic potential of epigenetic targeting therapeutics such as DNA methylation inhibitors, histone acetylase inhibitors, and miRNA replacement.