Inter- and intra-hemispheric lateralization alterations in auditory verbal hallucinations of Schizophrenia: insights from resting-state functional connectivity.

Auditory verbal hallucinations (AVHs) in schizophrenia are hypothesized to involve alterations in hemispheric lateralization, but the specific neural mechanisms remain unclear. This study investigated functional intra- and inter-hemispheric connectivity to identify lateralization patterns unique to AVHs. Resting-state fMRI data were collected from 60 schizophrenia patients with persistent AVHs (p-AVH group), 39 patients without AVHs (n-AVH group), and 59 healthy controls (HC group).

Exploring the relationship between electrophysiological measures of the electrically evoked auditory brainstem response and speech perception outcomes post-cochlear implantation.

Objectives: This study examined the relationships between electrophysiological measures of the electrically evoked auditory brainstem response (EABR) with speech perception measured in quiet after cochlear implantation (CI) to identify the ability of EABR to predict postoperative CI outcomes.

Methods: Thirty-four patients with congenital prelingual hearing loss, implanted with the same manufacturer's CI, were recruited. In each participant, the EABR was evoked at apical, middle, and basal electrode locations.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) has a complex etiology where insults in multiple pathways conspire to disrupt neuronal function, yet molecular changes underlying AD remain poorly understood. Previously, we performed mass-spectrometry on post-mortem human brain tissue to identify >40 protein co-expression modules correlated to AD pathological and clinical traits. Module 42 has the strongest correlation to AD pathology and consists of 32 proteins including SMOC1, a predicted driver of network behavior and potential biomarker for AD.

Basic Science and Pathogenesis.

Background: Alzheimer's Disease (AD) incidence is almost double in female than male, suggesting sex-specific AD risk genes remain unknown.

Method: We designed a statistical physics approach that exploits freely available but massive evolutionary and phylogenetic coupling data on sequence variation and speciation. These couplings lead to quantifiable values for the selection pressure exerted on the genes within a population.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD), an age-associated neurodegenerative disorder, is characterized by progressive neuronal loss and the accumulation of misfolded proteins such as amyloid-β and tau. While neuroinflammation, mediated by microglia and brain-resident macrophages, plays a pivotal role in AD pathogenesis, the intricate interactions among age, genes, and other risk factors remain elusive. Somatic mutations, known to accumulate with age, instigate clonal expansion across diverse cell types, impacting both cancer and non-cancerous conditions.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the deposition of amyloid-beta and hyperphosphorylated tau (P-tau) proteins in the brain. P-tau accumulates in neurons and is strongly associated with AD severity and affected brain regions. However, only a subset of neurons in AD exhibit tau pathology.

Basic Science and Pathogenesis.

Background: Previously, we found that germline C3 deletion protected cognition and hippocampal synapses in aged APP/PS1dE9 mice, despite increasing Aß plaques. Here, we crossed our C3 inducible conditional mouse model to APP knockin mice to determine whether global C3 lowering in an adult amyloid mouse model would be protective.

Methods: C3;Rosa26-Cre-ERT2 (C3iKO) mice were crossed to C3;APP mice to generate APP;C3iKO mice, which received 75 mg/kg tamoxifen (TAM; n = 16) or corn oil (CO; n = 15) for 5 days at 3.

Basic Science and Pathogenesis.

Background: In AD, neurofibrillary tangles (NFTs) develop earliest in the limbic system before spreading to neocortical areas. When accounting for covariates of AD pathology, such as age and APOE, there remains interindividual variation in NFT spread in the brain. We therefore used a machine-learning approach to investigate whether age-independent DNA methylation (DNAm) changes in brain associate with histopathological differences in AD.

Basic Science and Pathogenesis.

Background: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive head impact (RHI) although little is known about its molecular pathogenesis. Previous studies of single neurons showed that private somatic mutations increase both during normal aging and in neurodegenerative disorders, and show diverse mutational patterns.

Method: We applied two orthogonal single-nucleus whole-genome sequencing (snWGS) methods to neurons isolated from the prefrontal cortex of 15 individuals with CTE, and 4 individuals with RHI but no CTE diagnosis, and compared mutational rates and spectra with neurons from neurotypical controls and Alzheimer's disease (AD).

Basic Science and Pathogenesis.

Background: In Alzheimer's disease (AD), changes in the brain transcriptome are hypothesized to mediate the impact of neuropathology on cognition. Gene expression profiling from postmortem brain tissue is a promising approach to identify causal pathways; however, there are challenges to definitively resolve the upstream pathologic triggers along with the downstream consequences for AD clinical manifestations.

Method: We have functionally dissected 30 AD-associated gene coexpression modules using a cross-species strategy in Drosophila melanogaster models.

Basic Science and Pathogenesis.

Background: To date, Alzheimer's disease (AD) research has principally focused on neurons. In contrast, recent studies suggest that genetic mechanisms drive microglia towards prolonged inflammation in AD brains, exacerbating neurodegeneration. Indeed, many of the 70 disease-associated loci uncovered with genome-wide association studies (GWAS) reside near genes related to microglial function, such as TREM2.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) risk is markedly increased among APOE ε4/ε4 homozygotes. Previous studies of APOE genotype disclosure impact have included few ethnic minorities. This study addresses this gap by investigating the immediate impact of disclosing an APOE ε4/ε4 genotype in the Información de la Enfermedad de Alzheimer para Latinos (IDEAL) study, a Latino community-based study.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is characterized by neocortical dissemination of neurofibrillary tangles (NFTs) while primary age-related tauopathy (PART) has NFTs largely confined to the hippocampus and adjacent structures. Thus, PART and AD represent two extremes of a spectrum of NFT spread. We investigated epigenetic mechanisms of interindividual variation in NFT spread.

Development of a reference standard to assign bacterial versus viral infection etiology using an all-inclusive methodology for comparison of novel diagnostic tool performance.

Background: Diagnostic test evaluation requires a reference standard. We describe an approach for creating a reference standard for acute infection using unrestricted adjudication and apply it to compare biomarker tools.

Methods: Adults and children with suspected acute infection enrolled in three prospective studies at emergency departments and urgent cares were included.

Automated abdominal aortic calcification and major adverse cardiovascular events in people undergoing osteoporosis screening: the Manitoba Bone Mineral Density Registry.

Vertebral fracture assessment (VFA) images from bone density machines enable the automated machine learning assessment of abdominal aortic calcification (ML-AAC), a marker of cardiovascular disease (CVD) risk. The objective of this study was to describe the risk of a major adverse cardiovascular event (MACE, from linked health records) in patients attending routine bone mineral density (BMD) testing and meeting specific criteria based on age, BMD, height loss, or glucocorticoid use have a VFA in the Manitoba Bone Mineral Density Registry. The cohort included 10 250 individuals (mean 75.

Contiguous Xp21 deletion involving Duchenne muscular dystrophy and McLeod neuroacanthocytosis syndrome results in rapidly progressive and fatal cardiomyopathy.

Dilated cardiomyopathy is an expected manifestation and common cause of death in patients with Duchenne muscular dystrophy. We present an unusually rapid progression of cardiomyopathy in a boy with Duchenne muscular dystrophy. Expanded genetic testing revealed a contiguous Xp21 deletion involving dystrophin and XK genes, responsible for Duchenne muscular dystrophy and McLeod neuroacanthocytosis syndrome, respectively, resulting in a more severe cardiac phenotype.

Optimizing Management of Febrile Young Infants Without Serum Procalcitonin.

Background: Febrile young infants are at risk of invasive bacterial infections (IBIs; bacteremia or bacterial meningitis). American Academy of Pediatrics (AAP) guidelines recommend that when procalcitonin testing is unavailable, C-reactive protein (CRP), absolute neutrophil count (ANC) and temperature should be used to identify low-risk infants. We sought to determine the optimal combination of these inflammatory markers to predict IBI when procalcitonin is unavailable.

Comparison of two interferon-gamma release assays for pediatric tuberculosis infection.

Introduction: Identifying tuberculosis infection (TBI) using interferon-gamma release assays (IGRAs) is a primary component of clinical and public health efforts to prevent pediatric tuberculosis. Pediatric data comparing the two IGRAs in the United States are very limited. We compared the performance of the two IGRAs among a large pediatric cohort tested for TBI and assessed whether discordance might be due to quantitative results close to test cut-off values.

The substance-exposed birthing person-infant/child dyad and health information exchange in the United States.

Objective: Timely access to data is needed to improve care for substance-exposed birthing persons and their infants, a significant public health problem in the United States. We examined the current state of birthing person and infant/child (dyad) data-sharing capabilities supported by health information exchange (HIE) standards and HIE network capabilities for data exchange to inform point-of-care needs assessment for the substance-exposed dyad.

Material And Methods: A cross-map analysis was performed using a set of dyadic data elements focused on pediatric development and longitudinal supportive care for substance-exposed dyads (70 birthing person and 110 infant/child elements).

Infants admitted to Danish neonatal units demonstrate satisfactory growth independent of feeding type at discharge.

Aim: The aim was to investigate feeding type at discharge; exclusively breastfeeding (EBF), mixed breastfeeding (MBF), and formula milk feeding (FMF), factors associated with feeding type, and changes in weight-for-age z-score (ΔWAZ) in infants admitted to Danish neonatal units.

Methods: Using data from the Danish National Quality Database for Births and the Danish Newborn Quality Database, we included 8639 mother-infant dyads admitted ≥5 days between February 2019 and December 2021. We used logistic regression to investigate associations between maternal and infant factors and feeding type, and descriptive statistics to describe ΔWAZ and feeding type at discharge.

Accuracy of Capillary Blood for Assessing Vitamin A Nutritional Status Among Children Under 7 Years of Age: A Multicenter Study.

Vitamin A deficiency remains a major public health problem worldwide, particularly among young children. Capillary blood has the potential for application in vitamin A assessment. The aim of this study is to validate the accuracy of capillary blood for assessing vitamin A nutritional status among young children.

Abnormalities in cerebellar subregions' volume and cerebellocerebral structural covariance in autism spectrum disorder.

The cerebellum plays a crucial role in functions, including sensory-motor coordination, cognition, and emotional processing. Compared to the neocortex, the human cerebellum exhibits a protracted developmental trajectory. This delayed developmental timeline may lead to increased sensitivity of the cerebellum to external influences, potentially extending the vulnerability period for neurological disorders.

Phenotype Spectrum of TRPM3-Associated Disorders.

Objective: Monoallelic variants in the transient receptor potential melastatin-related type 3 gene (TRPM3) have been associated with neurodevelopmental manifestations, but knowledge on the clinical manifestations and treatment options is limited. We characterized the clinical spectrum, highlighting particularly the epilepsy phenotype, and the effect of treatments.

Methods: We analyzed retrospectively the phenotypes and genotypes of 43 individuals with TRPM3 variants, acquired from GeneMatcher and collaborations (n = 21), and through a systematic literature search (n = 22).

Neo-enhancers in T-cell acute lymphoblastic Leukaemia (T-ALL) and beyond.

T-cell acute lymphoblastic leukaemia (T-ALL) is a rare aggressive haematological malignancy characterised by the clonal expansion of immature T-cell precursors. It accounts for 15% of paediatric and 25% of adult ALL. T-ALL is associated with the overexpression of major transcription factors (TLX1/3, TAL1, HOXA) that drive specific transcriptional programmes and constitute the molecular classifying subgroups of T-ALL.

Effect of BMI and symptoms at celiac disease diagnosis on serology normalization after 2 years of a gluten-free diet in children.

Objectives: To determine if after 2 years of consuming a gluten-free diet post celiac disease diagnosis, pediatric patients who were overweight or obese at diagnosis are less likely to normalize celiac disease serologies as compared with those who were normal weight or underweight at diagnosis. Secondary aims include characterizing how initial symptoms at presentation predict body mass index (BMI) change and serology improvement over the first 2 years of being on a gluten-free diet following diagnosis of celiac disease.

Methods: A retrospective chart review was performed that included all biopsy-proven celiac disease patients followed at Stony Brook Children's Hospital's Celiac Disease Center diagnosed between the years 2007-2022.