Prosody or "melody in speech" in autism spectrum disorder (ASD) is often perceived as atypical. This study examined perception and production of statements and questions in 84 children, adolescents and adults with and without ASD, as well as participants' pitch direction discrimination thresholds. The results suggested that the abilities to discriminate (in both speech and music conditions), identify, and imitate statement-question intonation were intact in individuals with ASD across age cohorts. Sensitivity to pitch direction predicted performance on intonation processing in both groups, who also exhibited similar developmental changes. These findings provide evidence for shared mechanisms in pitch processing between speech and music, as well as associations between low- and high-level pitch processing and between perception and production of pitch.

Measurements of IgG antibodies to wild-type SARS-CoV-2 antigens can assess vaccine efficacy, but the absolute risk of Omicron symptomatic infection at different IgG levels for children and adolescents remains uncertain, as well as the minimum effective antibody level. We sought to determine the relationship between the tertiles of IgG antibodies to wild-type SARS-CoV-2 antigens and children with symptomatic infection of the pandemic and duration to negative conversion in China for the first time.

Cardiogenic shock (CS) is a complex state with many underlying causes and associated outcomes. It is still difficult to differentiate between various CS phenotypes. We investigated if the CS phenotypes with distinctive clinical profiles and prognoses might be found using the machine learning (ML) consensus clustering approach.

Multidrug-resistant organisms (MDROs) have emerged as an important cause of poor prognoses of patients in the intensive care unit (ICU). This study aimed to establish an easy-to-use nomogram for predicting the occurrence of MDRO colonization or infection in ICU patients.

BACKGROUND Face masks have become an important part of the COVID-19 prevention approach. This study aimed to explore the effect of wearing masks on exercise ability and ventilatory anaerobic threshold (VAT). MATERIAL AND METHODS Thirty-four young, healthy volunteers were included in this study, consisting of 18 men and 16 women. The subjects were randomized to perform 2 cardiopulmonary exercise tests (CPET) on a cycle ergometer with gas exchange analysis, one with and another without wearing a face mask (cross-over design). The general data for all subjects and indicators from the 2 exercise tests performed with and without wearing a face mask were collected. RESULTS In cardiopulmonary exercise tests, wearing a mask significantly (P<0.05) decreased peak indexes (eg, work rate (WR), oxygen consumption per kg body weight (VO₂/kg), heart rate (HR), ventilation per minute (VE) and carbon dioxide ventilation equivalent (VE/VCO₂)) and anaerobic threshold indexes (eg, WR, HR, VE, breath frequency (BF), dead space ratio (VD/VT), and VE/VCO₂). However, the PETCO₂ at peak was significantly higher. There was a positive linear correlation between WR difference and VO₂ difference at VAT (abbreviated as deltaWR@VAT and deltaVO₂@VAT, respectively) (r=0.495, P=0.003). Subgroup analysis of the VAT indexes showed that WR, VO₂/kg, and VE were significantly decreased in the advanced VAT group with mask compared with the stable VAT group with mask (P<0.05). Logistic regression showed that deltaVE, deltaBF, and deltaVE/VCO₂ had independent influences on VAT. CONCLUSIONS Wearing masks advances VAT in healthy young subjects during CPET. The advanced VAT was associated with changes in VE, BF, and VE/VCO₂ while wearing masks.

Many studies have announced that P50 inhibition defects represent sensory gating deficits in schizophrenia, but studies seldom have searched the correlation between P50 inhibition defects and the psychopathology or cognitive impairment of patients with first-episode, drug naïve (FEDN) of schizophrenia. In this study, we investigated the auditory sensory gating deficits in a large number of Han patients with FEDN schizophrenia and their correlation with clinical symptoms and cognitive impairment.

In humans, mutations in the transcription factor encoding gene, FOXP2, are associated with language and Autism Spectrum Disorders (ASD), the latter characterized by deficits in social interactions. However, little is known regarding the function of Foxp2 in male or female social behavior. Our previous studies in mice revealed high expression of Foxp2 within the medial subnucleus of the amygdala (MeA), a limbic brain region highly implicated in innate social behaviors such as mating, aggression, and parental care. Here, using a comprehensive panel of behavioral tests in male and female Foxp2 +/- heterozygous mice, we investigated the role Foxp2 plays in MeA-linked innate social behaviors. We reveal significant deficits in olfactory processing, social interaction, mating, aggressive, and parental behaviors. Interestingly, some of these deficits are displayed in a sex-specific manner. To examine the consequences of Foxp2 loss of function specifically in the MeA, we conducted a proteomic analysis of microdissected MeA tissue. This analyses revealed putative sex differences expression of a host of proteins implicated in neuronal communication, connectivity, and dopamine signaling. Consistent with this, we discovered that MeA Foxp2-lineage cells were responsive to dopamine with differences between males and females. Thus, our findings reveal a central and sex-specific role for Foxp2 in social behavior and MeA function.

IN BRIEF Appropriate management of hyperglycemia can significantly attenuate perinatal risks associated with a diagnosis of gestational diabetes mellitus (GDM). This article reports on a study evaluating the independent associations of maternal income and education with select measures of GDM management. This exploratory study demonstrates notable socioeconomic differences in select measures of GDM management. Additional studies are needed to determine the reasons for these differences and whether they exist in broader populations.

Elevated Golgi phosphoprotein 2 (GP73, also known as GOLPH2 or GOLM1) expression in serum and liver, which can be induced by viral infection and cytokine treatments, is intimately connected with liver disease, including acute hepatitis, cirrhosis and hepatocellular carcinoma (HCC). However, its pathogenic roles in hepatic diseases have never been clarified in detail. Here, we showed that the upregulated GP73 is indispensable for SREBPs activation and lipogenesis. Notably, GP73 overexpression enhanced SCAP-SREBPs binding and its Golgi trafficking even under cholesterol sufficiency. Consistent with these functional findings, GP73 blockage could alleviate tunicamycin-induced liver steatosis by reducing SREBPs activation. A significant positive correlation of GP73 with genes in lipid metabolism pathway was also identified in liver cancer based on data from The Cancer Genome Atlas (TCGA) dataset. Our findings revealed previously unrecognized role of GP73 in lipid metabolism.

Angelman syndrome (AS) is a neurodevelopmental disorder caused by loss of expression of the maternal copy of the UBE3A gene. Individuals with AS have a multifaceted behavioral phenotype consisting of deficits in motor function, epilepsy, cognitive impairment, sleep abnormalities, as well as other comorbidities. Effectively modeling this behavioral profile and measuring behavioral improvement will be crucial for the success of ongoing and future clinical trials. Foundational studies have defined an array of behavioral phenotypes in the AS mouse model. However, no single behavioral test is able to fully capture the complex nature of AS-in mice, or in children. We performed multidimensional analysis (principal component analysis + k-means clustering) to quantify the performance of AS model mice (n = 148) and wild-type littermates (n = 138) across eight behavioral domains. This approach correctly predicted the genotype of mice based on their behavioral profile with ~95% accuracy, and remained effective with reasonable sample sizes (n = ~12-15). Multidimensional analysis was effective using different combinations of behavioral inputs and was able to detect behavioral improvement as a function of treatment in AS model mice. Overall, multidimensional behavioral analysis provides a tool for evaluating the effectiveness of preclinical treatments for AS. Multidimensional analysis of behavior may also be applied to rodent models of related neurodevelopmental disorders, and may be particularly valuable for disorders where individual behavioral tests are less reliable than in AS.

Background: Only less than 40% of patients with Major depressive disorder (MDD) can achieve remission after several weeks of initial antidepressant treatment. Predicting whether the prescribed treatment is effective in the following course may help clinicians modify the treatment regimen in time, and reduce the staggering burden for patients and society. However, there are not yet reliable markers based on neurobiological change after a treatment regimen steadily applied, for predicting clinical treatment outcome. The striatal circuits often exhibit abnormality for MDD patients, and are implicated in antidepressant treatments. Methods: Nineteen first-episode drug-naive MDD patients (nine females, mean age was 30 years old) were recruited to undergo clinical symptom assessment and resting state fMRI scanning at baseline, after 2 and 8 weeks of treatment with duloxetine. A seed-based analysis was used to obtain functional connectivity (FC) maps of six sub-regions of the stratum, then we explored the relationship of 2-week changes of striatal FC with clinical symptom improvement after 8-week duloxetine treatment. Results: The results revealed that 2-week FC changes of the striatal cognitive and affective subdivisions with the frontoparietal regions positively correlated with 8-week symptom improvement. We also found that early FC changes between the striatal motor subdivision and the motor-related cortical regions negatively correlated with later symptom improvement. Conclusions: These findings suggest that change of the FC of the cortical-striatal circuits at the early stage of treatment is critical for later remission of MDD. Furthermore, the association between the FC change and symptom improvement may have significant implication for clinical practice to regard neural changes as reference for evaluating how antidepressant treatment works.

Mixed-type gastric adenocarcinoma (by Lauren Classification) has poor clinical outcomes with few targeted treatment options. The primary objective of this study was to find the prognostic factors, accurate treatment approaches, and effective postoperative adjuvant therapy strategies for patients with mixed-type gastric adenocarcinoma (GA). A microRNA sequencing data set and the corresponding clinical parameters of patients with gastric cancer were obtained from The Cancer Genome Atlas. Differentially expressed microRNAs (DEMs) of diffuse- and intestinal-type GA were, respectively, determined. Kaplan-Meier and log-rank tests were subsequently carried out to evaluate the prognostic relevance of each DEM. To study the common factors between diffuse- and intestinal-type GA, a pathway enrichment analysis was performed on the target genes of identified DEMs using the PANTHER database. After data preprocessing, we analyzed a total of 230 samples from 210 patients with GA. Eighty-six DEMs in diffuse-type GA samples and 59 DEMs in intestinal-type GA samples were, respectively, identified (p  2.0). The Kaplan-Meier survival method further screened out six prognosis-related DEMs for diffuse-type GA and seven prognosis-related DEMs for intestinal-type GA (p < 0.05). MiR-18a-5p was found to be the only common prognosis-related DEM between diffuse- and intestinal-type GA. The common signaling pathways further revealed that target genes of miR-18a-5p are involved in mixed-type GA progression. This study suggests that miR-18a-5p acts as a potential target for treatment, and common signal pathways provide a rich basis to seek reliable and effective molecular targets for the diagnosis, clinical treatment, and postoperative adjuvant therapy strategy of mixed-type GA.

The rise of high mountain chains is widely seen as one of the factors driving rapid diversification of land plants and the formation of biodiversity hotspots. Supporting evidence was reported for the impact of the rapid rise of the Andean mountains but this hypothesis has so far been less explored for the impact of the "roof of the world". The formation of the Himalaya, and especially the rise of the Qinghai-Tibetan Plateau in the recent 20 million years, altered the monsoon regimes that dominate the current climates of South East Asia. Here, we infer the hypothesis that the rise of Himalaya had a strong impact on the plant diversity in the biodiversity hotspot of the Southwest Chinese Mountains.

A two-stage case-control study was conducted to examine the association between six candidate U2-depedent spliceosome genes (SRSF1, SRSF2, SF3A1, SF3B1, SF1 and PRPF40B) and pancreatic cancer (PC). Subjects with one or two T alleles at rs2074733 in SF3A1 had a lower risk of PC compared to those with two C alleles in combined two populations (OR: 0.59, 95% confidence interval: 0.48-0.73, False discovery rate (FDR)-P = 1.5E-05). Moreover, the presence of the higher-risk genotype at rs2074733 plus smoking or drinking had synergic effects on PC risk. These findings illustrate that RNA splicing-related genes appear to be associated with the occurrence of PC, and show synergic interactions with smoking and drinking in the additive model. In the future, our novel findings should be further confirmed by functional studies and independent large-scale population studies.

As accessible diagnostic approaches fail to differentiate between ulcerative colitis (UC) and Crohn's colitis (CC) in one-third of patients with predominantly colonic inflammatory bowel disease (IBD), leading to inappropriate therapy, we aim to investigate the serum cytokine levels in these patients in search of molecular biometric markers delineating UC from CC.

Lysine-specific demethylase 6B (KDM6B) serves as a key mediator of gene transcription. It regulates expression of proinflammatory cytokines and chemokines in variety of diseases. Herein, the role and the underlying mechanisms of KDM6B in inflammatory pain were studied.

The objective of this study is to evaluate the effects of organic acids on piglet growth performance and health status. A total of 360 weanling pigs (5.3 ± 0.6 kg) were randomly allotted to 3 treatment groups with 12 replicates of 10 pigs/pen. Piglets were fed the same basal diet and given either water (control) or water plus 2.0 L/Ton organic acid (OA) blends, such as OA1 or OA2, respectively, for 7 weeks. Compared to the control, OA1 and OA2 improved growth performance and/or reduced the piglets' diarrhea rate during the various periods and improved small intestinal morphology at days 14 and/or 49. OA1 and OA2 also increased serum CAT and SOD activities and/or T-AOC and, as expected, decreased MDA concentration. Moreover, at day 14 and/or day 49, OA1 and OA2 increased the jejunal mRNA levels of host defense peptides (PBD1, PBD2, NPG1, and NPG3) and tight junction genes (claudin-1) and decreased that of cytokines (IL-1β and IL-2). Additionally, the two acidifiers regulated the abundance of several cecum bacterial genera, including Blautia, Bulleidia, Coprococcus, Dorea, Eubacterium, Subdoligranulum, and YRC2. In conclusion, both of the organic acid blends improved piglet growth performance and health status, potentially by regulating intestinal redox homeostasis, immunity, and microflora.

The deleted in azoospermia-like (DAZL) gene encoding an RNA binding protein is pivotal in gametogenesis in lots of species and also acts as a pre-meiosis marker. The current study was conducted to detect expression profiles and single nucleotide polymorphisms (SNPs) of DAZL in sheep using qPCR, DNA-pooled sequencing, improved multiplex ligase detection reaction (iMLDR®) and restriction fragment length polymorphism (RFLP) methods. The results confirmed that ovine DAZL showed the highest expression level at six-months of age across five developmental stage. At six-month stage, DAZL expressed primarily in testis across seven tissues analyzed. The abundance of DAZL in the large-testis group is higher than that in the small-testis group although it is not significant. In addition, six SNPs (SNP1-SNP6) were identified in DAZL. Of those, SNP1 (p < 0.05) and SNP6 (p < 0.01) were significantly correlated with the variation coefficient between left and right epididymis weight (VCTW). The current study implies DAZL may play important roles in testicular development and its SNPs are associated with testicular parameters, which supply important indicators for ram selection at early stage.

Corticotropin-releasing hormone (CRH) is known for its crucial role in the stress response system, which could induce pituitary adrenocorticotropic hormone (ACTH) secretion to promote glucocorticoid release in the adrenal gland. However, little is known about other pituitary actions of CRH in teleosts. Somatolactin is a fish-specific hormone released from the neurointermediate lobe (NIL) of the posterior pituitary. A previous study has reported that ACTH was also located in the pituitary NIL region. Interestingly, our present study found that CRH could significantly induce two somatolactin isoforms' (SLα and SLβ) secretion and synthesis in primary cultured grass carp pituitary cells. Pharmacological analysis further demonstrated that CRH-induced pituitary somatolactin expression was mediated by the AC/cAMP/PKA, PLC/IP3/PKC, and Ca2+/CaM/CaMK-II pathways. Finally, transcriptomic analysis showed that both SLα and SLβ should play an important role in the regulation of lipid metabolism in primary cultured hepatocytes. These results indicate that CRH is a novel stimulator of somatolactins in teleost pituitary cells, and somatolactins may participate in the stress response by regulating energy metabolism.

Epithelioid hemangioendothelioma (EHE) is a poorly understood and devastating vascular cancer. Sequencing of EHE has revealed a unique gene fusion between the Hippo pathway nuclear effector TAZ (WWTR1) and the brain-enriched transcription factor CAMTA1 in ∼90% of cases. However, it remains unclear whether the TAZ-CAMTA1 gene fusion is a driver of EHE, and potential targeted therapies are unknown. Here, we show that TAZ-CAMTA1 expression in endothelial cells is sufficient to drive the formation of vascular tumors with the distinctive features of EHE, and inhibition of TAZ-CAMTA1 results in the regression of these vascular tumors. We further show that activated TAZ resembles TAZ-CAMTA1 in driving the formation of EHE-like vascular tumors, suggesting that constitutive activation of TAZ underlies the pathological features of EHE. We show that TAZ-CAMTA1 initiates an angiogenic and regenerative-like transcriptional program in endothelial cells, and disruption of the TAZ-CAMTA1-TEAD interaction or ectopic expression of a dominant negative TEAD in vivo inhibits TAZ-CAMTA1-mediated transformation. Our study provides the first genetic model of a TAZ fusion oncoprotein driving its associated human cancer, pinpointing TAZ-CAMTA1 as the key driver and a valid therapeutic target of EHE.