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When applied to the TCGA cohort, the model yielded an AUROC of 0.969 (95% CI 0.950-0.987) and a Brier score of 0.109. On the post-Chernobyl cohort, it yielded an AUROC of 0.962 (95% CI 0.918-1) and a Brier score of 0.073. This algorithm also is robust against other various types of clinical scenarios, discriminating malignant from benign lesions as well as clinically aggressive thyroid cancer with poor prognosis from indolent ones. Furthermore, we discovered novel pathway alterations and prognostic signatures for PTC, which can provide directions for follow-up studies.Reduced amplitude of duration mismatch negativity (dMMN) has been reported in psychotic disorders and at-risk mental state (ARMS); however, few longitudinal MMN studies have examined the amplitude changes during the course of psychosis. Gypenoside L cell line We compared dMMN amplitude between ARMS individuals with later psychosis onset and those without, and we longitudinally examined potential dMMN changes around psychosis onset. Thirty-nine ARMS subjects and 22 healthy controls participated in this study. Of the 39 ARMS subjects, 11 transitioned to psychosis (at-risk mental state with later psychosis onset [ARMS-P]) during follow-up and 28 did not (at-risk mental state without later psychosis onset [ARMS-NP]). dMMN was measured twice using an auditory oddball paradigm with a mean interval of 2 years. Follow-up dMMN data were available for all but four ARMS-P subjects. dMMN amplitude at baseline was smaller in ARMS-P subjects compared with control and ARMS-NP subjects. Additionally, ARMS-P subjects displayed a longitudinal decline in dMMN amplitude, which was not present in control and ARMS-P subjects. We also observed a progressive decline in dMMN amplitude during the transition period, suggesting dynamic brain changes associated with the psychosis onset. Our findings implicate dMMN amplitude as a biological predictor of future psychosis onset in high-risk individuals, which may be used for early detection and intervention of psychosis.Oxytocin (OXT) is a nonapeptide that serves as a neuromodulator in the brain and a hormone participating in parturition and lactation in the periphery. The subiculum is the major output region of the hippocampus and an integral component in the networks that process sensory and motor cues to form a cognitive map encoding spatial, contextual, and emotional information. Whilst the subiculum expresses the highest OXT-binding sites and is the first brain region to be activated by peripheral application of OXT, the precise actions of OXT in the subiculum have not been determined. Our results demonstrate that application of the selective OXT receptor (OXTR) agonist, [Thr4,Gly7]-oxytocin (TGOT), excited subicular neurons via activation of TRPV1 channels, and depression of K+ channels. The OXTR-mediated excitation of subicular neurons required the functions of phospholipase Cβ, protein kinase C, and degradation of phosphatidylinositol 4,5-bisphosphate (PIP2). OXTR-elicited excitation of subicular neurons enhanced long-term potentiation via activation of TRPV1 channels. Our results provide a cellular and molecular mechanism to explain the physiological functions of OXT in the brain.

Licensure of a Group B streptococcus (GBS) polysaccharide-protein conjugate vaccine for protecting infants against invasive GBS disease (IGbsD) will likely need to be based on demonstrating vaccine safety in pregnant women, and benchmarking immunogenicity against a serological threshold associated with risk reduction of IGbsD. We investigated the association between naturally-derived GBS serotype-Ia and III IgG and risk reduction of IGbsD in infants’ ≤90 days of age.

In a matched case-control study (ClinicalTrials.gov NCT02215226), IGbsD cases were identified from a cohort of 38,233 mother-newborn dyads. Mothers colonized vaginally with serotype-Ia or III at birth, and their healthy infants were eligible as matched controls. GBS serotype-specific anti-capsular IgG was measured on maternal and cord blood/infant sera by multiplex Luminex assay; and the IgG threshold associated with 90% risk reduction of IGbsD derived by estimating absolute disease risk.

In infants born ≥34 weeks gestational age, cord-blood IgG geometric mean concentrations (GMC) were lower in cases than controls for serotype-Ia (0.05 vs. 0.50µg/ml; p=0.004) and III (0.20 vs. 0.38µg/ml; p=0.078). Cord-blood IgG concentration ≥1.04 and ≥1.53µg/ml were associated with 90% risk reduction of serotype-Ia and III IGbsD, respectively. The maternal sera IgG threshold associated with 90% risk reduction was ≥2.31 and ≥3.41µg/ml for serotype-Ia and III, respectively.

The threshold associated with a reduced risk for serotype-Ia and III IGbsD identified on infant sera supports the case for licensure of a GBS polysaccharide-protein conjugate vaccine based on immunogenicity evaluation benchmarked against the defined thresholds.

The threshold associated with a reduced risk for serotype-Ia and III IGbsD identified on infant sera supports the case for licensure of a GBS polysaccharide-protein conjugate vaccine based on immunogenicity evaluation benchmarked against the defined thresholds.Inferring how gene expression in a cell is influenced by cellular microenvironment is of great importance yet challenging. In this study, we present a single-cell RNA-sequencing data based multilayer network method (scMLnet) that models not only functional intercellular communications but also intracellular gene regulatory networks (https//github.com/SunXQlab/scMLnet). scMLnet was applied to a scRNA-seq dataset of COVID-19 patients to decipher the microenvironmental regulation of expression of SARS-CoV-2 receptor ACE2 that has been reported to be correlated with inflammatory cytokines and COVID-19 severity. The predicted elevation of ACE2 by extracellular cytokines EGF, IFN-γ or TNF-α were experimentally validated in human lung cells and the related signaling pathway were verified to be significantly activated during SARS-COV-2 infection. Our study provided a new approach to uncover inter-/intra-cellular signaling mechanisms of gene expression and revealed microenvironmental regulators of ACE2 expression, which may facilitate designing anti-cytokine therapies or targeted therapies for controlling COVID-19 infection.