Rare dysfunctional SCN2A variants are associated with malformation of cortical development.

Objective: SCN2A encodes the voltage-gated sodium (Na+) channel α subunit Na1.2, which is important for the generation and forward and back propagation of action potentials in neurons. Genetic variants in SCN2A are associated with a spectrum of neurodevelopmental disorders.

Metabotropic signaling within somatostatin interneurons controls transient thalamocortical inputs during development.

During brain development, neural circuits undergo major activity-dependent restructuring. Circuit wiring mainly occurs through synaptic strengthening following the Hebbian "fire together, wire together" precept. However, select connections, essential for circuit development, are transient.

Associations Between Radiation Oncologist Demographic Factors and Segmentation Similarity Benchmarks: Insights From a Crowd-Sourced Challenge Using Bayesian Estimation.

Purpose: The quality of radiotherapy auto-segmentation training data, primarily derived from clinician observers, is of utmost importance. However, the factors influencing the quality of clinician-derived segmentations are poorly understood; our study aims to quantify these factors.

Methods: Organ at risk (OAR) and tumor-related segmentations provided by radiation oncologists from the Contouring Collaborative for Consensus in Radiation Oncology data set were used.

Generalized anosognosia, anosodiaphoria, and visual hallucinations with bilateral enucleation after severe bifrontal brain injury: a case report describing similarities with and differences from Anton syndrome.

Visual anosognosia, associated with confabulations and cortical blindness in the context of occipital lobe injury, is known as Anton syndrome. Patients with this syndrome strongly deny their vision loss and confabulate to compensate for both visual loss and memory impairments. In this article, we present a case of a patient with some similarities to Anton syndrome, however, with several differences in clinical presentation.

Suppression of progesterone by influenza A virus mediates adverse maternal and fetal outcomes in mice.

Influenza A virus infection during pregnancy can cause adverse maternal and fetal outcomes but the mechanism responsible remains elusive. Infection of outbred mice with 2009 H1N1 at embryonic day (E) 10 resulted in significant maternal morbidity, placental tissue damage and inflammation, fetal growth restriction, and developmental delays that lasted through weaning. Restriction of pulmonary virus replication was not inhibited during pregnancy, but infected dams had suppressed circulating and placental progesterone (P4) concentrations that were caused by H1N1-induced upregulation of pulmonary cyclooxygenase (COX)-1-, but not COX-2-, dependent synthesis and secretion of prostaglandin (PG) F2α.

Assessing the benefits and risks of amantadine for irritability and aggression after traumatic brain injury.

Objective: To quantify the benefits versus harms of amantadine in the treatment of irritability and aggression following traumatic brain injury.

Methods: Secondary outcome data from a randomized controlled multisite trial of amantadine 100 mg twice daily were used to calculate number-needed-to-treat (NNT). Given prior findings of positive clinician-perceived effects and low incidence of adverse events, we hypothesized low number-needed-to-treat for benefit (NNTB; high benefit) and high number-needed-to-treat for harm (NNTH; low risk) based on the clinician ratings, supporting the use of amantadine in clinical practice.

Metabotropic signaling within somatostatin interneurons controls transient thalamocortical inputs during development.

During brain development, neural circuits undergo major activity-dependent restructuring. Circuit wiring mainly occurs through synaptic strengthening following the Hebbian "fire together, wire together" precept. However, select connections, essential for circuit development, are transient.

Suppression of progesterone by influenza A virus mediates adverse maternal and fetal outcomes in mice.

Influenza A virus infection during pregnancy can cause adverse maternal and fetal outcomes, but the mechanism responsible remains elusive. Infection of outbred mice with 2009 H1N1 at embryonic day (E) 10 resulted in significant maternal morbidity, placental tissue damage and inflammation, fetal growth restriction, and developmental delays that lasted through weaning. Restriction of pulmonary virus replication was not inhibited during pregnancy, but infected dams had suppressed circulating and placental progesterone (P4) concentrations that were caused by H1N1-induced upregulation of pulmonary cyclooxygenase (COX)-1, but not COX-2-, dependent synthesis and secretion of prostaglandin (PG) F2α.

Determining The Role Of Radiation Oncologist Demographic Factors On Segmentation Quality: Insights From A Crowd-Sourced Challenge Using Bayesian Estimation.

Background: Medical image auto-segmentation is poised to revolutionize radiotherapy workflows. The quality of auto-segmentation training data, primarily derived from clinician observers, is of utmost importance. However, the factors influencing the quality of these clinician-derived segmentations have yet to be fully understood or quantified.

Establishment of a Private Foundation-Academic Partnership to Promote Careers of Early-Stage Investigators Examining the Influence of Sex and Gender on Health and Health Care.

Biological sex and gender-based constructs contribute significantly to the diversity of disease outcomes and treatment responses across the life course. To promote research considering sex and gender, the National Institutes of Health (NIH) Office of Research on Women's Health (ORWH) launched the Specialized Centers of Research Excellence (SCORE) on sex differences program. The Career Enhancement Core (CEC) of the Johns Hopkins SCORE on Sex and Age Differences in Immunity to Influenza (SADII) partnered with the Foundation for Gender-Specific Medicine, which matched NIH funding to support seed grants.

Vitamin D levels and anxiety symptomatology in pregnancy and the postpartum.

Anxiety and vitamin D deficiency are both common in pregnancy, but research into the relationship between vitamin D levels and perinatal anxiety is sparse. We sought to examine whether an association exists and compare the distribution of vitamin D levels in women with and without anxiety symptoms. We analyzed 25-hydroxyvitamin D using ab213966 25(OH) vitamin D enzyme-linked immunosorbent assay in 54 women with and 47 women without anxiety symptoms at the first, second, and third trimesters and at 6 weeks postpartum.

Cortical somatostatin interneuron subtypes form cell-type-specific circuits.

The cardinal classes are a useful simplification of cortical interneuron diversity, but such broad subgroupings gloss over the molecular, morphological, and circuit specificity of interneuron subtypes, most notably among the somatostatin interneuron class. Although there is evidence that this diversity is functionally relevant, the circuit implications of this diversity are unknown. To address this knowledge gap, we designed a series of genetic strategies to target the breadth of somatostatin interneuron subtypes and found that each subtype possesses a unique laminar organization and stereotyped axonal projection pattern.

Nova proteins direct synaptic integration of somatostatin interneurons through activity-dependent alternative splicing.

Somatostatin interneurons are the earliest born population of cortical inhibitory cells. They are crucial to support normal brain development and function; however, the mechanisms underlying their integration into nascent cortical circuitry are not well understood. In this study, we begin by demonstrating that the maturation of somatostatin interneurons in mouse somatosensory cortex is activity dependent.

Prognostic Value of the Intermediate-risk Feature in Men with Favorable Intermediate-risk Prostate Cancer: Implications for Active Surveillance.

Background: Guidelines suggest that active surveillance (AS) may be considered for select patients with favorable intermediate-risk (fIR) prostate cancer.

Objective: To compare the outcomes between fIR prostate cancer patients included by Gleason score (GS) or prostate-specific antigen (PSA). Most patients are classified with fIR disease due to either a 3 + 4 = 7 GS (fIR-GS) or a PSA level of 10-20 ng/ml (fIR-PSA).

Biological Mechanisms in Pregnant Women With Anxiety (Happy Mother-Healthy Baby Supplement Study): Protocol for a Longitudinal Mixed Methods Observational Study.

Background: Anxiety and depression are common in the perinatal period and negatively affect the health of the mother and baby. Our group has developed "Happy Mother-Healthy Baby" (HMHB), a cognitive behavioral therapy-based psychosocial intervention to address risk factors specific to anxiety during pregnancy in low- and middle-income countries (LMICs).

Objective: The purpose of this study is to examine biological mechanisms that may be linked to perinatal anxiety in conjunction with a randomized controlled trial of HMHB in Pakistan.

Large scale crowdsourced radiotherapy segmentations across a variety of cancer anatomic sites.

Clinician generated segmentation of tumor and healthy tissue regions of interest (ROIs) on medical images is crucial for radiotherapy. However, interobserver segmentation variability has long been considered a significant detriment to the implementation of high-quality and consistent radiotherapy dose delivery. This has prompted the increasing development of automated segmentation approaches.

Anxiety in pregnancy and stress responsiveness: An exploratory study of heart rate variability, cortisol, and alpha-amylase in the third trimester.

The present study aimed to explore the association between anxiety symptoms, including sleep, and physiological stress responsiveness in pregnant women with and without anxiety, as identified by psychiatric diagnosis. Fifty-four pregnant women with (n = 25) and without (n = 29) anxiety completed a laboratory cognitive stressor (the Stroop Color-Word Task) during the third trimester. Heart rate variability (HRV) (as the root mean square of successive differences, RMSSD) was recorded during baseline, stressor, and recovery periods.

prospective acceptability benchmarking from the Contouring Collaborative for Consensus in Radiation Oncology crowdsourced initiative for multiobserver segmentation.

Purpose: Contouring Collaborative for Consensus in Radiation Oncology (C3RO) is a crowdsourced challenge engaging radiation oncologists across various expertise levels in segmentation. An obstacle to artificial intelligence (AI) development is the paucity of multiexpert datasets; consequently, we sought to characterize whether aggregate segmentations generated from multiple nonexperts could meet or exceed recognized expert agreement.

Approach: Participants who contoured region of interest (ROI) for the breast, sarcoma, head and neck (H&N), gynecologic (GYN), or gastrointestinal (GI) cases were identified as a nonexpert or recognized expert.

Altered extracellular mRNA communication in postpartum depression is associated with decreased autophagy.

We investigated whether extracellular RNA communication, which is a recently discovered mode of intercellular communication that is involved in a variety of important biological processes including pregnancy, is associated with postpartum depression (PPD). Extracellular RNA communication is increased during pregnancy and is involved in embryo implantation, uterine spiral artery remodeling, parturition, preterm birth, immunity, and the inflammatory response. Since immune anomalies are associated with PPD, we characterized the mRNA content of extracellular vesicles (EV) in a cohort of prospectively collected blood plasma samples at six time-points throughout pregnancy and the postpartum (2nd trimester, 3rd trimester, 2 weeks postpartum, 6 weeks postpartum, 3 months postpartum, and 6 months postpartum) in an academic medical setting from women who went on to develop PPD (N = 7, defined as euthymic in pregnancy with postpartum-onset depressive symptoms assessed by Edinburgh Postnatal Depression Scale ≥13 at any postpartum time point) and matched unaffected controls (N = 7, defined as euthymic throughout pregnancy and postpartum).

The immune phenotype of perinatal anxiety.

Background: Immune dysregulation has been linked to both psychiatric illness and pregnancy morbidity, including perinatal depression, but little is known about the immune phenotype of perinatal anxiety. Here, we sought to identify the unique immune profile of antenatal anxiety.

Materials And Methods: Pregnant women (n = 107) were followed prospectively at 2nd and 3rd trimesters (T2, T3) and 6 weeks postpartum (PP6).

Feasibility and Utility of a Flexible Outcome Assessment Battery for Longitudinal Traumatic Brain Injury Research: A TRACK-TBI Study.

The effects of traumatic brain injury (TBI) are difficult to measure in longitudinal cohort studies, because disparate pre-injury characteristics and injury mechanisms produce variable impairment profiles and recovery trajectories. In preparation for the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study, which followed patients with injuries ranging from uncomplicated mild TBI to coma, we designed a multi-dimensional Flexible outcome Assessment Battery (FAB). The FAB relies on a decision-making algorithm that assigns participants to a Comprehensive (CAB) or Abbreviated Assessment Battery (AAB) and guides test selection across all phases of recovery.

Association Between Prostate-Specific Antigen Screening and Prostate Cancer Mortality Among Non-Hispanic Black and Non-Hispanic White US Veterans.

Importance: Black men have higher prostate cancer incidence and mortality than non-Hispanic White men. However, Black men have been underrepresented in clinical trials of prostate-specific antigen (PSA) screening; thus, there is a lack of data to guide screening recommendations for this population.

Objective: To assess whether PSA screening is associated with reduced risk of prostate cancer-specific mortality (PCSM) among non-Hispanic Black men.