Comparison of different group-level templates in gradient-based multimodal connectivity analysis.

The study of large-scale brain connectivity is increasingly adopting unsupervised approaches that derive low-dimensional spatial representations from high-dimensional connectomes, referred to as gradient analysis. When translating this approach to study interindividual variations in connectivity, one technical issue pertains to the selection of an appropriate group-level template to which individual gradients are aligned. Here, we compared different group-level template construction strategies using functional and structural connectome data from neurotypical controls and individuals with autism spectrum disorder (ASD) to identify between-group differences.

A generative model of the connectome with dynamic axon growth.

Connectome generative models, otherwise known as generative network models, provide insight into the wiring principles underpinning brain network organization. While these models can approximate numerous statistical properties of empirical networks, they typically fail to explicitly characterize an important contributor to brain organization-axonal growth. Emulating the chemoaffinity-guided axonal growth, we provide a novel generative model in which axons dynamically steer the direction of propagation based on distance-dependent chemoattractive forces acting on their growth cones.

Revisiting Injectable Estrogen Dosing Recommendations for Gender-Affirming Hormone Therapy.

Injectable estrogens are options for gender-affirming hormone therapy per guidelines, which suggest intramuscular dosages of 5-30 mg every 2 weeks or 2-10 mg weekly with estradiol cypionate or valerate interchangeably. Data among transgender and gender-diverse patients are limited due to local unavailability and concerns around laboratory assay variability and estradiol (E2) level fluctuation. We note a concerning trend where patients are prescribed high-dose injections based on the guidelines leading to serum E2 levels well above the range recommended in the same guidelines.

Gender-Affirming Hormone Therapy Is Associated with Increased Odds of Screening for Sexually Transmitted Infections in a Clinical Cohort of Transgender and Nonbinary Adults.

Purpose: Transgender and nonbinary adults (TNB) are disproportionately burdened by sexually transmitted infections (STI) and the human immunodeficiency virus (HIV). This study investigated whether gender-affirming hormone therapy was associated with TNB adults' odds of screening for STI and HIV.

Methods: Longitudinal data came from the electronic medical records of TNB primary care patients receiving care at two community health centers located in Boston, Massachusetts, and New York City, New York, between January 2013 and December 2019.

Women and the Heart: Webcast April 16 2024.

This 62-minute webcast features a conversation about "Women and the Heart: Gender-Related Differences in Cardiovascular Care"-the focus of Issue 20.2. Led by the issue's editor, the discussion engages the authors on emerging themes and lessons learned while researching and writing the articles.

The association between behavioral habits and physical health status in prostate cancer patients: a large US national health-related survey.

Background: The impact of behavioral habits such as exercise on the physical health of prostate cancer (PCa) patients is poorly understood. We aimed to investigate PCa patients' exercise habits and the association between exercise and self-reported physical health status.

Methods: The 2016-2020 Behavioral Risk Factor Surveillance System (BRFSS) databases were used to identify men with a history of PCa.

Polygenic score distribution differences across European ancestry populations: implications for breast cancer risk prediction.

Background: The 313-variant polygenic risk score (PRS) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS across different European populations which could influence risk estimation has not been performed.

Methods: We explored the distribution of PRS across European populations using genotype data from 94,072 females without breast cancer diagnosis, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 223,316 females without breast cancer diagnosis from the UK Biobank.

Accelerated development of cardiovascular risk factors mediates risk for major adverse cardiovascular events in posttraumatic stress disorder.

Background: Individuals with posttraumatic stress disorder (PTSD) have high rates of cardiovascular disease (CVD) and increased cardiometabolic CVD risk factors (CVDRFs, e.g., hypertension, hyperlipidemia, or diabetes mellitus).

- a large-scale dataset of 3D medical shapes for computer vision.

Objectives: The shape is commonly used to describe the objects. State-of-the-art algorithms in medical imaging are predominantly diverging from computer vision, where voxel grids, meshes, point clouds, and implicit surface models are used. This is seen from the growing popularity of ShapeNet (51,300 models) and Princeton ModelNet (127,915 models).

Association of Biopsy-proven Nonalcoholic Fatty Liver Disease with Obesity and Apolipoproteins.

Background And Aims: Insulin resistance is considered the most important key mechanism in the development of nonalcoholic fatty liver disease (NAFLD). Some studies have reported that hyperinsulinemia decreases the hepatic secretion of apolipoprotein (Apo) B. Chronic hyperinsulinemia in NAFLD may be responsible for the accumulation of triglycerides in hepatocytes.

Mitochondrial transplantation normalizes transcriptomic and proteomic shift associated with ischemia reperfusion injury in neonatal hearts donated after circulatory death.

Heart transplantation remains the ultimate treatment strategy for neonates and children with medically refractory end-stage heart failure and utilization of donors after circulatory death (DCD) can expand th donor pool. We have previously shown that mitochondrial transplantation preserves myocardial function and viability in neonatal swine DCD hearts to levels similar to that observed in donation after brain death (DBD). Herein, we sought to investigate the transcriptomic and proteomic pathways implicated in these phenotypic changes using ex situ perfused swine hearts.

Brain phosphoproteomic analysis identifies diabetes-related substrates in Alzheimer's disease pathology in older adults.

Introduction: Type 2 diabetes increases the risk of Alzheimer's disease (AD) dementia. Insulin signaling dysfunction exacerbates tau protein phosphorylation, a hallmark of AD pathology. However, the comprehensive impact of diabetes on patterns of AD-related phosphoprotein in the human brain remains underexplored.

Introduction to the DETeCD-ADRD special issue.

This special issue contains multiple articles related to the DETeCD-ADRD guideline.

Predicting lack of clinical improvement following varicose vein ablation using machine learning.

Objective: Varicose vein ablation is generally indicated in patients with active/healed venous ulcers. However, patient selection for intervention in individuals without venous ulcers is less clear. Tools that predict lack of clinical improvement (LCI) following vein ablation may help guide clinical decision-making but remain limited.

Discovery of a Pseudomonas aeruginosa-specific small molecule targeting outer membrane protein OprH-LPS interaction by a multiplexed screen.

The surge of antimicrobial resistance threatens efficacy of current antibiotics, particularly against Pseudomonas aeruginosa, a highly resistant gram-negative pathogen. The asymmetric outer membrane (OM) of P. aeruginosa combined with its array of efflux pumps provide a barrier to xenobiotic accumulation, thus making antibiotic discovery challenging.

The T cell receptor sequence influences the likelihood of T cell memory formation.

The amino acid sequence of the T cell receptor (TCR) varies between T cells of an individual's immune system. Particular TCR residues nearly guarantee mucosal-associated invariant T (MAIT) and natural killer T (NKT) cell transcriptional fates. To define how the TCR sequence affects T cell fates, we analyze the paired αβTCR sequence and transcriptome of 961,531 single cells.

The Role of Podocytes in Lupus Pathology.

Purpose Of Review: Kidney injury due to lupus nephritis (LN) is a severe and sometimes life-threatening sequela of systemic lupus erythematosus. Autoimmune injury to podocytes has been increasingly demonstrated to be a key driver of LN-related kidney injury because these cells play key roles in glomerular filtration barrier homeostasis. Irreparable podocyte injury impairs these processes and can lead to proteinuria, which is an indicator of poor prognosis in LN.

Family Genetic Risk Communication and Reverse Cascade Testing in the BabySeq Project.

Purpose: Genomic sequencing of newborns (NBSeq) can initiate disease surveillance and therapy for children, and may identify at-risk relatives through reverse cascade testing. We explored genetic risk communication and reverse cascade testing among families of newborns who underwent exome sequencing and had a risk for autosomal dominant disease identified.

Methods: We conducted semi-structured interviews with parents of newborns enrolled in the BabySeq Project who had a pathogenic or likely-pathogenic (P/LP) variant associated with an autosomal dominant (AD) childhood- and/or adult-onset disease returned.

Effectiveness and Safety of IVIG for the Treatment of HMGCR Immune-Mediated Necrotizing Myopathy.

Introduction/aims: Immune-mediated necrotizing myopathy (IMNM) is an autoimmune myopathy. We aimed to compare clinical outcomes in patients with antibodies against 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) treated on immunotherapy regimens with and without maintenance intravenous immunoglobulin (IVIG). The secondary aim was to assess outcomes in a subset that received IVIG monotherapy.

Identification of shared genetic etiology of cardiovascular and cerebrovascular diseases through common cardiometabolic risk factors.

Cardiovascular diseases (CVDs) and cerebrovascular diseases (CeVDs) are closely related vascular diseases, sharing common cardiometabolic risk factors (RFs). Although pleiotropic genetic variants of these two diseases have been reported, their underlying pathological mechanisms are still unclear. Leveraging GWAS summary data and using genetic correlation, pleiotropic variants identification, and colocalization analyses, we identified 11 colocalized loci for CVDs-CeVDs-BP (blood pressure), CVDs-CeVDs-LIP (lipid traits), and CVDs-CeVDs-cIMT (carotid intima-media thickness) triplets.

Modulating cell-free DNA biology as the next frontier in liquid biopsies.

Technical advances over the past two decades have enabled robust detection of cell-free DNA (cfDNA) in biological samples. Yet, higher clinical sensitivity is required to realize the full potential of liquid biopsies. This opinion article argues that to overcome current limitations, the abundance of informative cfDNA molecules - such as circulating tumor DNA (ctDNA) - collected in a sample needs to increase.

Associations of blood pressure with white matter hyperintensities later in life; influence of short-term menopausal hormone therapy.

Objective: To assess the association of systolic and diastolic blood pressure (SBP and DBP) in recently menopausal women with white matter hyperintensity (WMH) volume later in life and determine whether short-term menopausal hormone therapy (mHT) modifies these associations.

Methods: Kronos Early Estrogen Prevention Study (KEEPS) was a multicenter, randomized, double-blinded, placebo-controlled 4-year mHT trial (oral conjugated equine estrogens or transdermal 17β-estradiol). KEEPS continuation was an observational follow-up of the participants 10 years after the end of mHT.