Long-term complications in classic galactosemia are not progressive.

Classic galactosemia (CG) is a potentially lethal genetic disorder that results from profound deficiency of galactose-1-P uridylyltransferase. Despite early detection and life-long dietary restriction of galactose, which is the current standard of care, many patients with CG grow to experience a range of long-term developmental complications that can include difficulties with speech/voice/language, cognitive, motor, and psychosocial outcomes, among other problems. That these complications are common in CG is well-documented, but whether they are also progressive has been a point of controversy for decades.

Fellowship of two rings: Unprecedented insights into the structure of the yeast nuclear pore complex.

Akey et al. use complementary experimental approaches and AI-based structure prediction to reveal new details of the structure of the yeast nuclear pore complex, providing key insights into evolution, assembly, and nucleocytoplasmic transport mechanisms.

Political representation and perinatal outcomes to Black, White, and Hispanic people in Georgia: a cross-sectional study.

Purpose: Our goal was to estimate differences in perinatal outcomes by racial differences in political representation, a measure of structural racism.

Methods: We gathered data on the racial composition of county-level elected officials for all counties in Georgia (n = 159) in 2022. We subtracted the percent of non-White elected officials from the percent of non-White residents to calculate the "representation difference," with greater positive values indicating a larger disparity.

sRNAfrag: A pipeline and suite of tools to analyze fragmentation in small RNA sequencing data.

Fragments derived from small RNAs such as small nucleolar RNAs hold biological relevance. However, they remain poorly understood, calling for more comprehensive methods for analysis. We developed sRNAfrag, a standardized workflow and set of scripts to quantify and analyze sRNA fragmentation of any biotype.

Adjuvant Therapy for High-Risk Melanoma: An In-Depth Examination of the State of the Field.

The consideration of systemic adjuvant therapy is recommended for patients with stage IIB-IV melanoma who have undergone surgical resection due to a heightened risk of experiencing melanoma relapse and mortality from melanoma. Adjuvant therapy options tested over the past three decades include high-dose interferon-α, immune checkpoint inhibitors (pembrolizumab, nivolumab), targeted therapy (dabrafenib-trametinib for BRAF mutant melanoma), radiotherapy and chemotherapy. Most of these therapies have been demonstrated to enhance relapse-free survival (RFS) but with limited to no impact on overall survival (OS), as reported in randomized trials.

Emerging Role of Epigenetic Modifiers in Breast Cancer Pathogenesis and Therapeutic Response.

Breast cancer pathogenesis, treatment, and patient outcomes are shaped by tumor-intrinsic genomic alterations that divide breast tumors into molecular subtypes. These molecular subtypes often dictate viable therapeutic interventions and, ultimately, patient outcomes. However, heterogeneity in therapeutic response may be a result of underlying epigenetic features that may further stratify breast cancer patient outcomes.

Nicardipine is a putative EED inhibitor and has high selectivity and potency against chemoresistant prostate cancer in preclinical models.

Background: It is imperative to develop novel therapeutics to overcome chemoresistance, a significant obstacle in the clinical management of prostate cancer (PCa) and other cancers.

Methods: A phenotypic screen was performed to identify novel inhibitors of chemoresistant PCa cells. The mechanism of action of potential candidate(s) was investigated using in silico docking, and molecular and cellular assays in chemoresistant PCa cells.

Food insecurity among Asian Americans: A scoping review protocol.

Introduction: Food insecurity is prevalent in the U.S. and is associated with deleterious health, behavioral, and social consequences.

The LIN28B-let-7-PBK pathway is essential for group 3 medulloblastoma tumor growth and survival.

Children with Group 3 medulloblastoma (G3 MB) have a very poor prognosis, and many do not survive beyond 5 years after diagnosis. A factor that may contribute to this is the lack of available targeted therapy. Expression of protein lin-28 homolog B (LIN28B), a regulator of developmental timing, is upregulated in several cancers, including G3 MB, and is associated with worse survival in this disease.

Seizure onset and offset pattern determine the entrainment of the cortex and substantia nigra in the nonhuman primate model of focal temporal lobe seizures.

Temporal lobe (TL) epilepsy is the most common form of drug-resistant epilepsy. A major focus of human and animal studies on TLE network has been the limbic circuit and the structures composing the temporal lobe. However, there is also evidence suggesting an active role of the basal ganglia in the propagation and control of temporal lobe seizures.

A minimal human physiologically based kinetic model of thyroid hormones and chemical disruption of plasma thyroid hormone binding proteins.

The thyroid hormones (THs), thyroxine (T4) and triiodothyronine (T3), are under homeostatic control by the hypothalamic-pituitary-thyroid axis and plasma TH binding proteins (THBPs), including thyroxine-binding globulin (TBG), transthyretin (TTR), and albumin (ALB). THBPs buffer free THs against transient perturbations and distribute THs to tissues. TH binding to THBPs can be perturbed by structurally similar endocrine-disrupting chemicals (EDCs), yet their impact on circulating THs and health risks are unclear.

Bromocriptine monotherapy overcomes prostate cancer chemoresistance in preclinical models.

Chemoresistance is a major obstacle in the clinical management of metastatic, castration-resistant prostate cancer (PCa). It is imperative to develop novel strategies to overcome chemoresistance and improve clinical outcomes in patients who have failed chemotherapy. Using a two-tier phenotypic screening platform, we identified bromocriptine mesylate as a potent and selective inhibitor of chemoresistant PCa cells.

Impact of the CARE Tipping Point Program in Nepal on adolescent girls' agency and risk of child, early, or forced marriage: Results from a cluster-randomized controlled trial.

Background: Girl child, early, and forced marriage (CEFM) persists in South Asia, with long-term effects on well-being. CARE's Tipping Point Initiative (TPI) sought to address the gender norms and inequalities underlying CEFM by engaging participant groups on programmatic topics and supporting community dialogue to build girls' agency, shift power relations, and change norms. We assessed impacts of the CARE TPI on girls' multifaceted agency and risk of CEFM in Nepal.

Predicting glycemic control status and high blood glucose levels through voice characteristic analysis in patients with cystic fibrosis-related diabetes (CFRD).

Cystic fibrosis-related diabetes (CFRD) is associated with reduced life expectancy in adults with cystic fibrosis (CF). Voice analysis may be a convenient method for diagnosing and monitoring CFRD. This study aims to determine the relationship between voice characteristics and markers of glucose and glycemic control and to identify if voice analysis can predict high blood glucose levels and glycemic control in adults with CFRD.

The comorbidity of depression and neurocognitive disorder in persons with HIV infection: call for investigation and treatment.

Depression and neurocognitive disorder continue to be the major neuropsychiatric disorders affecting persons with HIV (PWH). The prevalence of major depressive disorder is two to fourfold higher among PWH than the general population (∼6.7%).

Important Correlates of Purpose in Life in a Diverse Population-Based Cohort: A Machine Learning Approach.

Background: Purpose-in-life (PiL) refers to the tendency to derive meaning and purpose from daily life experiences. Individuals with higher PiL were more likely to have better physical, mental, and cognitive health in prospective studies. Here, we aimed to identify important correlates of PiL among people of diverse backgrounds.

A Healthy Diet is Associated with a Lower Risk of Hepatic Fibrosis.

Background: Higher diet quality is associated with a lower risk of NAFLD.

Objectives: We examined the relationship between diet quality and hepatic fibrosis.

Methods: We analyzed cross-sectional associations between 3 a priori diet quality scores-the Dietary Approaches to Stop Hypertension (DASH) score, the Alternative Healthy Eating Index (AHEI), and a modified Mediterranean-style Diet Score (MDS)-and hepatic fat [controlled attenuation parameter (CAP)] and fibrosis [liver stiffness measurement (LSM)] measured by vibration-controlled transient elastography (VCTE) in 2532 Framingham Heart Study (FHS) participants and 3295 participants of the National Health and Nutrition Examination Survey (NHANES).

What do Trauma Surgery Textbooks Teach About Racial Disparities and the Roots of Violence?

This study presents a formal text analysis of trauma surgery textbooks. We examine passages that describe disparities or mechanisms of injury, and we report types of underlying causes and preventative interventions discussed. Trauma textbooks were drawn from an industry-standard list used by medical libraries.

Salt-Containing Recipes in Popular Magazines with the Highest Circulation in the United States Do Not Specify Iodized Salt in the Ingredient List.

Iodine deficiency is a public health problem in the US, with the iodine status of women of reproductive age decreasing in recent years. This may be attributable to voluntary salt iodization in the US. Magazines, a common source of recipes and nutritional information, may influence salt use and iodine intake.

Racial and ethnic diversity of classic and clinical variant galactosemia in the United States.

Classic and clinical variant galactosemia (CG/CVG) are allelic, autosomal recessive disorders that result from deficiency of galactose-1-P uridylyltransferase (GALT). CG/CVG has been reported globally among patients of diverse ancestries, but most large studies of outcomes have included, almost exclusively, patients categorized as White or Caucasian. As a first step to explore whether the cohorts studied are representative of the CG/CVG population at large, we sought to define the racial and ethnic makeup of CG/CVG newborns in a diverse population with essentially universal newborn screening (NBS) for galactosemia: the United States (US).

Risk of violent behaviour in young people at clinical high risk for psychosis from the North American Prodrome Longitudinal Studies consortium.

Aim: Although violent behaviour has been studied in schizophrenia, violence risk has received little attention in individuals at clinical high risk for psychosis (CHR). This manuscript aims to report and discuss the overall results of the Structured Assessment for Violence Risk in Youth (SAVRY) from the NAPLS-3 project to explore the risk of violence in CHR youth and to determine the relationship between SAVRY violence risk scores, psychosis risk symptoms, and global functioning. We hypothesized that CHR young people are at higher risk of violence as compared to healthy comparison participants due to a similarity between risk factors for psychosis and risk factors for violence, and that this risk is associated with greater severity of symptoms, poor functioning, and risk for conversion to psychosis.

Clinical characteristics and molecular etiology of partial 17α-hydroxylase deficiency diagnosed in 46,XX patients.

Introduction: Complete 17α-hydroxylase deficiency (17OHD) is relatively common, with typical juvenile female genitalia, severe hypertension, hypokalemia, and the absence of sexual development, but partial (or non-classical) 17OHD (p17OHD) is extremely rare. The p17OHD patients can present with a broad spectrum of symptoms in 46,XX karyotype including various degree of spontaneous breast development after puberty, recurrent ovarian cysts, oligomenorrhea and infertility depending on specific gene mutations and other influencing factors.

Methods: This paper is a retrospective analysis of p17OHD cases from 1997 to 2021 in a Chinese tertiary hospital.

Cerebral Aβ deposition in an Aβ-precursor protein-transgenic rhesus monkey.

With the ultimate goal of developing a more representative animal model of Alzheimer's disease (AD), two female amyloid-β-(Aβ) precursor protein-transgenic (APPtg) rhesus monkeys were generated by lentiviral transduction of the gene into rhesus oocytes, followed by fertilization and embryo transfer. The -transgene included the AD-associated Swedish K670N/M671L and Indiana V717F mutations () regulated by the human polyubiquitin-C promoter. Overexpression of was confirmed in lymphocytes and brain tissue.