Biological validation of peak-width of skeletonized mean diffusivity as a VCID biomarker: The MarkVCID Consortium.

Background: Peak-width of skeletonized mean diffusivity (PSMD), a neuroimaging marker of cerebral small vessel disease (SVD), has shown excellent instrumental properties. Here, we extend our work to perform a biological validation of PSMD.

Methods: We included 396 participants from the Biomarkers for Vascular Contributions to Cognitive Impairment and Dementia (MarkVCID-1) Consortium and three replication samples (Cohorts for Heart and Aging Research in Genomic Epidemiology = 6172, Rush University Medical Center = 287, University of California Davis Alzheimer's Disease Research Center = 567).

Trajectory of beta cell function and insulin clearance in stage 2 type 1 diabetes: natural history and response to teplizumab.

Aims/hypothesis: We aimed to analyse TrialNet Anti-CD3 Prevention (TN10) data using oral minimal model (OMM)-derived indices to characterise the natural history of stage 2 type 1 diabetes in placebo-treated individuals, to describe early metabolic responses to teplizumab and to explore the predictive capacity of OMM measures for disease-free survival rate.

Methods: OMM-estimated insulin secretion, sensitivity and clearance and the disposition index were evaluated at baseline and at 3, 6 and 12 months post randomisation in placebo- and teplizumab-treated groups, and, within each group, in slow- and rapid-progressors (time to stage 3 disease >2 or 2 years). OMM metrics were also compared with the standard AUC C-peptide.

A worldwide study of subcortical shape as a marker for clinical staging in Parkinson's disease.

Alterations in subcortical brain regions are linked to motor and non-motor symptoms in Parkinson's disease (PD). However, associations between clinical expression and regional morphological abnormalities of the basal ganglia, thalamus, amygdala and hippocampus are not well established. We analyzed 3D T1-weighted brain MRI and clinical data from 2525 individuals with PD and 1326 controls from 22 global sources in the ENIGMA-PD consortium.

Spontaneous cerebrovascular reactivity at rest in older adults with and without mild cognitive impairment and memory deficits.

Introduction: Older adults with mild cognitive impairment (MCI) exhibit deficits in cerebrovascular reactivity (CVR), suggesting CVR is a biomarker for vascular contributions to MCI. This study examined if spontaneous CVR is associated with MCI and memory impairment.

Methods: One hundred sixty-one older adults free of dementia or major neurological/psychiatric disorders were recruited.

Protective effects of Shexiang-Tongxin dropping pill against acute myocardial infarction in rats through inhibition of apoptosis and ERK/MAPK signaling pathways.

Acute myocardial infarction (AMI) remains a significant health challenge globally, highlighting the ongoing need for effective treatments. Shexiang-Tongxin dropping pill (STDP) is widely utilized as a therapeutic option for AMI in China and Southeast Asia. However, the intricate mechanisms of action of STDP against AMI remain largely unknown.

A Partially Randomized Patient Preference, Sequential, Multiple-Assignment, Randomized Trial Design Analyzed via Weighted and Replicated Frequentist and Bayesian Methods.

Results from randomized control trials (RCTs) may not be representative when individuals refuse to be randomized or are excluded for having a preference for which treatment they receive. If trial designs do not allow for participant treatment preferences, trials can suffer in accrual, adherence, retention, and external validity of results. Thus, there is interest surrounding clinical trial designs that incorporate participant treatment preferences.

Structural brain connectivity does not associate with childhood trauma in individuals with schizophrenia.

Background: Schizophrenia is a brain dysconnectivity disorder. However, it is not well understood whether the experience of childhood trauma (CT) affects dysconnectivity in individuals with schizophrenia (SZ). Using a network-based approach, we examined whether self-reported CT would explain additional variance compared to whole-brain topology and structural connectivity changes in SZ versus healthy controls (HC).

Exploring multimodal biomarker candidates of post-traumatic epilepsy following moderate to severe traumatic brain injury: A systematic review and meta-analysis.

This review systematically analyzes potential biomarker candidates for post-traumatic epilepsy (PTE) in humans who have experienced moderate to severe traumatic brain injury (TBI). Focusing on biomarkers across biofluid-based protein, genetic, neuroimaging, and neurophysiological categories, this review distinguishes between TBI patients who develop PTE and those who do not. The review adheres to established methodologies outlined in the Cochrane Handbook for Systematic Reviews of Interventions.

Carrier-free immobilized enzyme for ligand fishing of carbonic anhydrase inhibitors in Salvia miltiorrhiza.

The traditional method for natural products discovering could be time-consuming and labor-intensive, thus ligand fishing has attracted a lot of attention as a fast-screening method. Nevertheless, ligand fishing often relied on immobilized enzyme with solid carriers, which can be expensive and complicated to prepare. In this study, a carrier-free enzyme immobilization technology, cross-linked enzyme aggregates (CLEAs), was introduced by preparing carbonic anhydrase cross-linked enzyme aggregates (CA-CLEAs), aiming to develop a method for ligand fishing that is simpler, faster and more cost-effective.

ENIGMA-Meditation: Worldwide Consortium for Neuroscientific Investigations of Meditation Practices.

Meditation is a family of ancient and contemporary contemplative mind-body practices that can modulate psychological processes, awareness, and mental states. Over the last 40 years, clinical science has manualized meditation practices and designed various meditation interventions that have shown therapeutic efficacy for disorders including depression, pain, addiction, and anxiety. Over the past decade, neuroimaging has been used to examine the neuroscientific basis of meditation practices, effects, states, and outcomes for clinical and nonclinical populations.

Cortico-limbic volume abnormalities in late life depression are distinct from β amyloid and white matter pathologies.

This study was conducted to clarify patterns of cortico-limbic volume abnormalities in late life depression (LLD) relative to non-depressed (ND) adults matched for amyloid β (Aβ) deposition and to evaluate the relationship of volume abnormalities with cognitive performance. Participants included 116 LLD and 226 ND. Classification accuracy of LLD status was estimated using area under the receiver operator characteristic curve.

Fully automatic deep convolutional approaches for the screening of neurodegeneratives diseases using multi-view OCT images.

The prevalence of neurodegenerative diseases (NDDs) such as Alzheimer's (AD), Parkinson's (PD), Essential tremor (ET), and Multiple Sclerosis (MS) is increasing alongside the aging population. Recent studies suggest that these disorders can be identified through retinal imaging, allowing for early detection and monitoring via Optical Coherence Tomography (OCT) scans. This study is at the forefront of research, pioneering the application of multi-view OCT and 3D information to the neurological diseases domain.

White matter microstructure in obesity and bipolar disorders: an ENIGMA bipolar disorder working group study in 2186 individuals.

Although specific risk factors for brain alterations in bipolar disorders (BD) are currently unknown, obesity impacts the brain and is highly prevalent in BD. Gray matter correlates of obesity in BD have been well documented, but we know much less about brain white matter abnormalities in people who have both obesity and BD. We obtained body mass index (BMI) and diffusion tensor imaging derived fractional anisotropy (FA) from 22 white matter tracts in 899 individuals with BD, and 1287 control individuals from 20 cohorts in the ENIGMA-BD working group.

APOE ε4 and Dietary Patterns in Relation to Cognitive Function: An Umbrella Review of Systematic Reviews.

Context: Carrying the apolipoprotein ε4 allele (APOE ε4) is the strongest genetic risk factor for late-onset Alzheimer's disease. There is some evidence suggesting that APOE ε4 may modulate the influence of diet on cognitive function.

Objective: This umbrella review of systematic reviews evaluates the existing literature on the effect of dietary interventions on cognitive and brain-imaging outcomes by APOE status.

Looking back at the TEDDY study: lessons and future directions.

The goal of the TEDDY (The Environmental Determinants of Diabetes in the Young) study is to elucidate factors leading to the initiation of islet autoimmunity (first primary outcome) and those related to progression to type 1 diabetes mellitus (T1DM; second primary outcome). This Review outlines the key findings so far, particularly related to the first primary outcome. The background, history and organization of the study are discussed.

Age-related decline in blood-brain barrier function is more pronounced in males than females in parietal and temporal regions.

The blood-brain barrier (BBB) plays a pivotal role in protecting the central nervous system (CNS), and shielding it from potential harmful entities. A natural decline of BBB function with aging has been reported in both animal and human studies, which may contribute to cognitive decline and neurodegenerative disorders. Limited data also suggest that being female may be associated with protective effects on BBB function.

Carotid single- and dual-layer stents reduce the wall adhesion of platelets by influencing flow and cellular transport.

An ongoing thrombosis on a ruptured atherosclerotic plaque in the carotid may cause stroke. The primary treatment for patients with tandem lesion is stenting. Dual-layer stents have been introduced as an alternative to single-layer stents for elective and emergent carotid artery stenting.

Effects of one-night partial sleep deprivation on perivascular space volume fraction: Findings from the Stockholm Sleepy Brain Study.

Increased waste clearance in the brain is thought to occur most readily during late-stage sleep (stage N3). Sleep deprivation disrupts time spent in deeper sleep stages, fragmenting the clearance process. Here, we have utilized the publicly available Stockholm Sleepy Brain Study to investigate whether various sleep-related measures are associated with changes in perivascular space (PVS) volume fraction following a late-night short-sleep experiment.

Demystifying the effect of receptive field size in U-Net models for medical image segmentation.

Purpose: Medical image segmentation is a critical task in healthcare applications, and U-Nets have demonstrated promising results in this domain. We delve into the understudied aspect of receptive field (RF) size and its impact on the U-Net and attention U-Net architectures used for medical imaging segmentation.

Approach: We explore several critical elements including the relationship among RF size, characteristics of the region of interest, and model performance, as well as the balance between RF size and computational costs for U-Net and attention U-Net methods for different datasets.

Enhancement of early proximal caries annotations in radiographs: introducing the Diagnostic Insights for Radiographic Early-caries with micro-CT (ACTA-DIRECT) dataset.

Background: Proximal caries datasets for training artificial intelligence (AI) algorithms commonly include clinician-annotated radiographs. These conventional annotations are susceptible to observer variability, and early caries may be missed. Micro-computed tomography (CT), while not feasible in clinical applications, offers a more accurate imaging modality to support the creation of a reference-standard dataset for caries annotations.

Human Anti-Glycan Reactivity is Driven by the Selection of B cells Utilizing Private Antibody Gene Rearrangements that are Affinity Maturated in Germinal Centers.

The human antibody repertoire is broadly reactive with carbohydrate antigens represented in the universe of all living things, including both the host/self- as well as the commensal microflora-derived glycomes. Here we have used BCR receptor cloning and expression together with single-cell transcriptomics to analyze the B cell repertoire to the ubiquitous N-acetyl-D-glucosamine (GlcNAc) epitope in human cohorts and dissect the immune phylogeny of this predominant class of antibodies. We find that circulating anti-GlcNAc B cells exhibiting canonical BMem phenotypes emerge rapidly after birth and couple this observation with evidence for germinal center-dependent affinity maturation of carbohydrate-specific B cell receptors during early childhood.

Risk of celiac disease autoimmunity is modified by interactions between CD247 and environmental exposures.

Season of birth, viral infections, HLA haplogenotypes and non-HLA variants are implicated in the development of celiac disease and celiac disease autoimmunity, suggesting a combined role of genes and environmental exposures. The aim of the study was to further decipher the biological pathways conveying the season of birth effect in celiac disease autoimmunity to gain novel insights into the early pathogenesis of celiac disease. Interactions between season of birth, genetics, and early-life environmental factors on the risk of celiac autoimmunity were investigated in the multicenter TEDDY birth cohort study.