Experimental Validation of the Neurotrophic Factor-α1 Binding Site on the Serotonin Receptor 1E (HTR1E) Responsible for β-Arrestin Activation and Subsequent Neuroprotection.

Stress, such as neuroexcitotoxicity and oxidative stress, as well as traumatic brain injury, will result in neurodegeneration. Deciphering the mechanisms underlying neuronal cell death will facilitate the development of drugs that can promote neuronal survival and repair through neurogenesis. Many growth and trophic factors, including transforming growth factors (TGFs), insulin-like growth factors (IGFs), epidermal growth factor (EGF), fibroblast growth factor 2 (FGF2), and brain-derived neurotrophic factor (BDNF), are known to play a role in neuroprotection and neurogenesis.

The evolutionary history of metastatic pancreatic neuroendocrine tumours reveals a therapy driven route to high-grade transformation.

Tumour evolution with acquisition of more aggressive disease characteristics is a hallmark of disseminated cancer. Metastatic pancreatic neuroendocrine tumours (PanNETs) in particular may progress from a low/intermediate to a high-grade disease. The aim of this work was to understand the molecular mechanisms underlying metastatic progression as well as PanNET transformation from a low/intermediate to a high-grade disease.

Tracking temporal variations of fatality and symptomology correlated with COVID-19 dominant variants and vaccine effectiveness in the United States.

Introduction: We described how COVID-19 fatality and symptoms varied by dominant variant and vaccination in the US.

Methods: Using the Restricted Access Dataset from the US CDC (1/1/2020-10/20/2022), we conducted a cross-sectional study assessing differences in COVID-19 deaths, severity indicators (hospitalization, ICU, pneumonia, abnormal X-ray, acute respiratory distress syndrome, mechanical ventilation) and 12 mild symptoms by dominant variant/vaccination periods using logistic regression after controlling for confounders.

Results: We found the highest fatality during the dominant periods of Wild (4.

Essential Role of the RIα Subunit of cAMP-Dependent Protein Kinase in Regulating Cardiac Contractility and Heart Failure Development.

Background: The heart expresses 2 main subtypes of cAMP-dependent protein kinase (PKA; type I and II) that differ in their regulatory subunits, RIα and RIIα. Embryonic lethality of RIα knockout mice limits the current understanding of type I PKA function in the myocardium. The objective of this study was to test the role of RIα in adult heart contractility and pathological remodeling.

Case Series: Variants in Four Patients with Metastatic Pheochromocytoma.

Few reports have highlighted the rare presence of somatic variants in clinically aggressive, metastatic pheochromocytoma/paraganglioma (PCC/PGL); however, none have addressed detailed clinical presentation (including biochemistry and imaging) and management of these patients. Here, we address these clinical features and management based on four PCC patients with somatic variants from our National Institutes of Health PCC/PGL cohort. A total of 192 patients underwent exome sequencing (germline, somatic, or both), and four males were found to have somatic variants (with additional somatic and oncogenic variants in patients 2 and 4, respectively).

Ethical and epistemic costs of a lack of geographical and cultural diversity in developmental science.

Increasing geographical and cultural diversity in research participation has been a key priority for psychological researchers. In this article, we track changes in participant diversity in developmental science over the past decade. These analyses reveal surprisingly modest shifts in global diversity of research participants over time, calling into question the generalizability of our empirical foundation.

Proteomic Profiles of Maternal Plasma Extracellular Vesicles for Prediction of Preeclampsia.

Problem: Preeclampsia is a heterogeneous syndrome of diverse etiologies and molecular pathways leading to distinct clinical subtypes. Herein, we aimed to characterize the extracellular vesicle (EV)-associated and soluble fractions of the maternal plasma proteome in patients with preeclampsia and to assess their value for disease prediction.

Method Of Study: This case-control study included 24 women with term preeclampsia, 23 women with preterm preeclampsia, and 94 healthy pregnant controls.

Regulatory elements in (7q21.3) locus contribute to genetic control of coronal nonsyndromic craniosynostosis and bone density-related traits.

Purpose: The etiopathogenesis of coronal nonsyndromic craniosynostosis (cNCS), a congenital condition defined by premature fusion of 1 or both coronal sutures, remains largely unknown.

Methods: We conducted the largest genome-wide association study of cNCS followed by replication, fine mapping, and functional validation of the most significant region using zebrafish animal model.

Results: Genome-wide association study identified 6 independent genome-wide-significant risk alleles, 4 on chromosome 7q21.

VMAP: Vaginal Microbiome Atlas during Pregnancy.

Objectives: To enable interactive visualization of the vaginal microbiome across the pregnancy and facilitate discovery of novel insights and generation of new hypotheses.

Material And Methods: Vaginal Microbiome Atlas during Pregnancy (VMAP) was created with R shiny to generate visualizations of structured vaginal microbiome data from multiple studies.

Results: VMAP (http://vmapapp.

Establishing NIH Community Implementation Programs to improve maternal health.

The United States has seen increasing trends of maternal mortality in recent years. Within this health crisis there are large disparities whereby underserved and minoritized populations are bearing a larger burden of maternal morbidity and mortality. While new interventions to improve maternal health are being developed, there are opportunities for greater integration of existing evidence-based interventions into routine practice, especially for underserved populations, including those residing in maternity care deserts.

On the Optimal Combination of Elliptically Distributed Biomarkers to Improve Diagnostic Accuracy.

Diagnostic biomarkers play a critical role in biomedical research, particularly for the diagnosis and prediction of diseases, etc. To enhance diagnostic accuracy, extensive research about combining multiple biomarkers has been developed based on the multivariate normality, which is often not true in practice, as most biomarkers follow distributions that deviate from normality. While the likelihood ratio combination is recognized to be the optimal approach, it is complicated to calculate.

Do maternal and paternal education protect against developmental delays?

Background: Parental education is linked to child development and wellbeing, but unique and combined contributions of maternal and paternal education have rarely been studied.

Aims: This study assessed the individual and joint associations of maternal and paternal education on children's odds of a probable developmental delay.

Methods And Procedures: Mothers (N = 3566) from the Upstate KIDS cohort study reported on theirs and the father's highest level of education and completed the Ages and Stages Questionnaires up to 7 times when the child was 4- to 36-months-old.

From palm to practice: prescription digital therapeutics for mental and brain health at the National Institutes of Health.

Prescription Digital Therapeutics (PDTs) are emerging as promising tools for treating and managing mental and brain health conditions within the context of daily life. This commentary distinguishes PDTs from other Software as Medical Devices (SaMD) and explores their integration into mental and brain health treatments. We focus on research programs and support from the National Institutes of Health (NIH), discussing PDT research supported by the NIH's National Institute on Child Health and Development (NICHD), National Institute of Mental Health (NIMH), and National Institute on Aging (NIA).

Six induced pluripotent stem cell lines from fibroblasts of individuals with CLN3-related conditions.

Primary fibroblasts from six individuals with CLN3-related conditions were used to generate induced pluripotent stem cell (iPSC) lines CHDTRi001-B, CHDTRi002-B, CHDTRi003-A, CHDTRi004-B, CHDTRi005-A, and CHDTRi006-E through the expression of four reprogramming factors: human OCT3/4, KLF4, SOX2, and c-MYC. The iPSC lines were characterized to confirm their pluripotency via immunocytochemistry, flow cytometry, and teratoma formation. Genomic stability, cell line identity, and CLN3 genotype were confirmed.

Attachment security, environmental adversity, and fast life history behavioral profiles in human adolescents.

One species-general life history (LH) principle posits that challenging childhood environments are coupled with a fast or faster LH strategy and associated behaviors, while secure and stable childhood environments foster behaviors conducive to a slow or slower LH strategy. This coupling between environments and LH strategies is based on the assumption that individuals' internal traits and states are independent of their external surroundings. In reality, individuals respond to external environmental conditions in alignment with their intrinsic vitality, encompassing both physical and mental states.

Dietary Sugar and Saturated Fat Consumption Associated with the Gastrointestinal Microbiome during Pregnancy.

Background: Growing evidence supports changes in the gastrointestinal microbiome over the course of pregnancy may have an impact on the short- and long-term health of both the mother and the child.

Objective: Our objective was to explore the association of diet quality, as measured by the Healthy Eating Index (HEI), with the composition and gene ontology (GO) representation of microbial function in the maternal gastrointestinal microbiome during pregnancy.

Methods: We conducted a retrospective, observational analysis of n = 185 pregnant participants in the Pregnancy Eating Attributes Study.

Diet quality from early pregnancy through 1-y postpartum: a prospective cohort study.

Background: Although diet quality during pregnancy and postpartum is important for multiple parent and child outcomes, within-person changes in diet quality throughout these periods have not been extensively examined.

Objectives: This study investigated diet quality from early pregnancy through 1 y postpartum and examined differences by sociodemographic characteristics in participants receiving obstetric care in Chapel Hill, North Carolina, United States.

Methods: Participants completed 24-h dietary recalls at 6 study visits (each pregnancy trimester and 6 wk, 6 mo, and 1 y postpartum) (n = 383).

Efficacy of pharmacologic hemorrhage prophylactics in second-trimester abortions: a systematic review.

Objective: This study aimed to evaluate prophylactic uterotonics, antifibrinolytic medications, and vasoconstrictive agents in the prevention of hemorrhage during second-trimester abortions.

Data Sources: PubMed, Embase (Elsevier platform), Evidence-Based Medicine Reviews (Ovid platform), and Web of Science were searched from database creation to October 30, 2023.

Study Eligibility Criteria: Randomized controlled trials, cohort studies, case-control studies, and case series evaluating pregnant individuals (between 13 0/7 and 27 6/7 weeks of gestation) who underwent dilation and evacuation and received prophylactic uterotonics (methylergonovine, carboprost, oxytocin, or misoprostol), antifibrinolytic medications (tranexamic acid), or vasoconstrictive agents (vasopressin, lidocaine with epinephrine) were included in the study.

CHARMM at 45: Enhancements in Accessibility, Functionality, and Speed.

Since its inception nearly a half century ago, CHARMM has been playing a central role in computational biochemistry and biophysics. Commensurate with the developments in experimental research and advances in computer hardware, the range of methods and applicability of CHARMM have also grown. This review summarizes major developments that occurred after 2009 when the last review of CHARMM was published.

Management and follow-up strategies for patients with head and neck paraganglioma.

Objective: Head-neck paragangliomas (HNPGLs) are rare tumors with approximately half arising due to germline pathogenic variants (PVs) in succinate dehydrogenase genes (SDHx). Patients with HNPGL have heterogeneous propensity to recur and metastasize. Thus, we aim to assess prevalence and predictors of recurrent (RD) and/or metastatic disease in patients with and without SDHx-related HNPGLs.