Munksgaardupton7225

Microscopic sperm detection is an important task in sexual assault cases. In some instances, the samples contain no or only low amounts of semen. Therefore, the biological material is transferred onto a glass slide and needs to be manually scanned using an optical microscope. This work can be very time consuming, especially when no spermatozoa is present. In such a case, the result needs to be validated. In this article we show how convolutional neural networks can perform this task and how they can reduce the scanning time by locating the sperm cells on images taken under the microscope. For this purpose, we trained a VGG19 network and a VGG19 variation with 1942 images, some containing sperm cells and some not.

The difficulty in interpreting somatic alterations is correlated with the increase in sequencing panel size. To correctly guide the clinical management of patients with cancer, there needs to be accurate classification of pathogenicity followed by actionability assessment. Here, we describe a specific detailed workflow for the classification of the pathogenicity of somatic variants in cancer into five categories benign, likely benign, unknown significance, likely pathogenicand pathogenic.

Classification is obtained by combining a set of eight relevant criteria in favour of either a pathogenic or a benign effect (pathogenic stand-alone, pathogenic very strong, pathogenic strong, pathogenic moderate, pathogenic supporting, benign supporting, benign strong and benign stand-alone).

Our guide is concordant with the ACMG/AMP 2015 guidelines for germline variants. Interpretation of somatic variants requires considering specific criteria, such as the disease and therapeutic context, co-occurring genomic events in the tumour when availableand the use of cancer-specific variant databases. In addition, the gene role in tumorigenesis (oncogene or tumour suppressor gene) also needs to be taken into consideration.

Our classification could contribute to homogenize best practices on somatic variant pathogenicity interpretation and improve interpretation consistency both within and between laboratories.

Our classification could contribute to homogenize best practices on somatic variant pathogenicity interpretation and improve interpretation consistency both within and between laboratories.Schizophrenia is thought to be a neurodevelopmental disorder with neuronal migration, differentiation and maturation disturbances. Tau is a microtubule-associated protein with a crucial role in these processes. Lower circulating tau levels have been reported in adults with schizophrenia, but this association has not been investigated in adolescent psychosis. We aimed to test the hypotheses that a) adolescents with early-onset psychosis (EOP; age of onset less then 18 years) display lower plasma tau concentrations compared to healthy controls, and b) among patients with psychosis, tau levels are linked to structural brain measures associated with the microtubule-associated tau (MAPT) gene and psychosis. We included 37 adolescent patients with EOP (mean age 16.4 years) and 59 adolescent healthy controls (mean age 16.2 years). We investigated putative patient-control differences in plasma total tau concentrations measured by a Single molecule array (Simoa) immunoassay. We explored the correlations between tau and selected structural brain measures based on T1-weighted MRI scans processed in FreeSurfer v6.0. We found significantly lower plasma tau concentrations in patients compared to healthy controls (p = 0.017, partial eta-squared = 0.061). Tau was not associated with antipsychotic use or the antipsychotic dosage. Among patients but not healthy controls, tau levels were positively correlated with the cortical orbitofrontal surface area (p = 0.013, R-squared = 0.24). The results are suggestive of a tau-related neurodevelopmental disturbance in adolescent psychosis.Substance use disorders (SUDs) are important risk factors for suicide, yet little is known about how suicide risks vary by specific SUDs. We examined these risks for the first time in a large general population to facilitate comparisons across SUDs. A national cohort study was conducted of all 6,947,191 adults in Sweden. SUDs (opioid, sedative/hypnotic, hallucinogen, cannabis, amphetamine, cocaine, and alcohol use disorders) were identified using inpatient, outpatient, and crime data, and suicide deaths using nationwide death data with follow-up during 2003-2016. Cox regression was used to compute hazard ratios (HRs) for suicide death while adjusting for sociodemographic factors and psychiatric, SUD, and somatic comorbidities. Co-sibling analyses assessed for confounding by unmeasured shared familial (genetic and/or environmental) factors. In 79.8 million person-years of follow-up, 15,616 (0.2%) suicide deaths were identified. All SUDs were associated with significantly increased risks, with HRs ranging from 12- to 26-fold and 2.5- to 6.4-fold before and after adjusting for covariates, respectively. After adjusting for all covariates, opioid use disorder was the strongest risk factor (HR, 6.39; 95% CI, 5.53-7.38) (P ≤ 0.002 compared with any other SUD), followed by sedative/hypnotic use disorder (4.62; 4.06-5.27) (P ≤ 0.009 compared with any other SUD except opioid or hallucinogen). Most associations persisted after controlling for shared familial factors, consistent with causal effects. In this large national cohort, all SUDs were associated with significantly increased risks of suicide death, especially opioid and sedative/hypnotic use disorders. These findings may improve risk stratification and inform interventions to prevent suicide in the highest-risk subgroups with SUDs.Blinded, site-independent (remote) ratings from audio-digital recordings of site-based Positive and Negative Syndrome Scale (PANSS) interviews were obtained in a 5-week, randomized, double-blinded study assessing the safety, tolerability, and efficacy of KarXT (a fixed combination of xanomeline and trospium chloride) in hospitalized adults with schizophrenia experiencing an acute exacerbation of psychosis (EMERGENT-1; ClinicalTrials.gov identifier NCT3697252). The blinded site-independent raters had no knowledge of site location, study visit, drug vs. placebo assignment, or any treatment emergent adverse events (TEAEs). Concordance analyses of 561 paired site-based and site-independent PANSS ratings across all visits revealed a high correlation (ICC = 0.775). Paired scoring differences were positively correlated with the PANSS total score (Spearman's rho = 0.37, p less then 0.0001). Paired PANSS scores were available from 148 subjects at both the baseline and end of study visits (KarXT = 72, Placebo = 76). Site-based PANSS total scores (primary aim) revealed a significantly greater improvement from baseline in the KarXT group compared to the placebo group (p less then 0.0001). The blinded site-independent PANSS total scores derived from listening to and scoring the recorded site-based PANSS interviews replicated this finding (p less then 0.001) and yielded an overall predictive value of 85.1% for matching the site-based response/non-response outcomes. TEAE's have the potential to "unblind" site-based ratings. In this study, the site-independent raters were blinded to TEAEs, affirmed the site-based PANSS ratings, and mitigated concerns about possible functional unblinding of site-based raters. This method of blinded assessment via audio-digital recordings may have utility for other studies concerned with ratings precision and/or functional unblinding.The severity of major depressive disorder (MDD) can be aggravated by gastrointestinal (GI) symptoms, but the neuroimaging mechanism underlying GI symptoms still remains unclear. In this study, we recruited 52 medication-free and first-episode MDD patients (35 with GI symptoms and 17 without GI symptoms) and 28 age-, sex-, and education-matched healthy controls to explore the inter-group differences in neuroimaging findings. All the participants underwent resting-state functional magnetic resonance imaging (fMRI) scan, and the functional connectivities that were reported to be abnormal in MDD were our focus of exploration. Voxel-mirrored homotopic connectivity (VMHC) method was used to explore the interhemispheric homotopic functional connectivity of all the subjects. Patients with MDD showed significantly different VMHC in brain regions in the default mode network (DMN), including the middle frontal gyrus, precuneus, inferior parietal lobule, and posterior cingulate cortex. Patients with GI symptoms exhibited significantly decreased interhemispheric homotopic functional connectivity in the middle frontal gyrus and superior frontal gyrus, compared with patients without GI symptoms. These results suggested that the DMN is involved in the neuropathology of MDD. Selleck Panobinostat Interhemispheric homotopic connectivity in specific regions could be applied as a biomarker to distinguish MDD patients with GI symptoms from those without GI symptoms.Hypothyroidism is a condition that affects multiple systems, including the central nervous system, causing, for example, cognitive deficits closely related to Alzheimer's disease. The flavonoid chrysin is a natural compound associated with neuronal improvement in several experimental models. Here, we evaluated the effect of chrysin on cognitive impairment in hypothyroid female mice by exploring neuroplasticity. Hypothyroidism was induced by continuous exposure to 0.1% methimazole (MTZ) in drinking water for 31 days. On the 32nd day, the animals showed low plasma levels of thyroid hormones (hypothyroid mice) than the control group (euthyroid mice). Subsequently, mice were intragastrically administered with vehicle or chrysin (20 mg/kg) once a day for 28 consecutive days. At the end of the treatments, behavioral tests were performed open-field test (OFT) and morris water maze (MWM). Then, the levels of neurotrophins (BDNF and NGF) in the hippocampus and prefrontal cortex were measured and tested the affinity of chrysin with neurotrophinergic receptors through molecular docking. Hypothyroid mice showed memory deficit in the MWM and reduced neurotrophins levels in the hippocampus and prefrontal cortex, meanwhile, the chrysin treatment was able to reversed the deficit of spatial memory function and increased the levels of BDNF in hipocamppus and NGF in both structures. Additionally, molecular docking analysis showed that chrysin potentially binds to the active site of the TrkA, TrkB, and p75NTR receptors. Together, these findings suggest that chrysin reversed behavioral and neurochemical alterations associated with memory deficit induced by hypothyroidism, possibly by modulating synaptic plasticity in the neurotrophinergic system.

Research on predictors and risk of recurrence after suicide attempt from China is lacking. This study aims to identify risk factors and develop prediction models for recurrent suicidal behavior among suicide attempters using Cox proportional hazard (CPH) and machine learning methods.

The prospective cohort study included 1103 suicide attempters with a maximum follow-up of 10 years from rural China. Baseline characteristics, collected by face-to-face interviews at least 1 month later after index suicide attempt, were used to predict recurrent suicidal behavior. CPH and 3 machine learning algorithms, namely, the least absolute shrinkage and selection operator, random survival forest, and gradient boosting decision tree, were used to construct prediction models. Model performance was accessed by concordance index (C-index) and the time-dependent area under the receiver operating characteristic curve (AUC) value for discrimination, and time-dependent calibration curve along with Brier score for calibration.

The median follow-up time was 7.