An agarose fluidic chip for high-throughput organoid imaging.

Modern cell and developmental biology increasingly relies on 3D cell culture systems such as organoids. However, routine interrogation with microscopy is often hindered by tedious, non-standardized sample mounting, limiting throughput. To address these bottlenecks, we have developed a pipeline for imaging intact organoids in flow, utilizing a transparent agarose fluidic chip that enables efficient and consistent recordings with theoretically unlimited throughput.

FITM2 deficiency results in ER lipid accumulation, ER stress, and reduced apolipoprotein B lipidation and VLDL triglyceride secretion in vitro and in mouse liver.

Objective: Triglycerides (TGs) associate with apolipoprotein B100 (apoB100) to form very low density lipoproteins (VLDLs) in the liver. The repertoire of factors that facilitate this association is incompletely understood. FITM2, an integral endoplasmic reticulum (ER) protein, was originally discovered as a factor participating in cytosolic lipid droplet (LD) biogenesis in tissues that do not form VLDL.

Targeting the transferrin receptor to transport antisense oligonucleotides across the mammalian blood-brain barrier.

Antisense oligonucleotides (ASOs) are promising therapeutics for treating various neurological disorders. However, ASOs are unable to readily cross the mammalian blood-brain barrier (BBB) and therefore need to be delivered intrathecally to the central nervous system (CNS). Here, we engineered a human transferrin receptor 1 (TfR1) binding molecule, the oligonucleotide transport vehicle (OTV), to transport a tool ASO across the BBB in human TfR knockin (TfR KI) mice and nonhuman primates.

Sex and mental health are related to subcortical brain microstructure.

Some mental health problems such as depression and anxiety are more common in females, while others such as autism and attention deficit/hyperactivity (AD/H) are more common in males. However, the neurobiological origins of these sex differences are poorly understood. Animal studies have shown substantial sex differences in neuronal and glial cell structure, while human brain imaging studies have shown only small differences, which largely reflect overall body and brain size.

Health and well-being needs of Indigenous adolescents: a protocol for a scoping review of qualitative studies.

Introduction: Improving the health of Indigenous adolescents is central to addressing the health inequities faced by Indigenous peoples. To achieve this, it is critical to understand what is needed from the perspectives of Indigenous adolescents themselves. There have been many qualitative studies that capture the perspectives of Indigenous young people, but synthesis of these has been limited to date.

Achieving High-Precision, Low-Cost Microfluidic Chip Fabrication with Flexible PCB Technology.

Soft lithography has long remained the state of the art to generate the necessary micropatterning for molded microfluidic (MF) chips. Previous attempts to use printed circuit boards (PCBs) as a cheap and accessible alternative to expensive lithographed molds for the production of PDMS MF chip prototypes have shown their limitations. A more in-depth exploration of using PCBs as a mold substrate and a novel methodology of using flexible PCBs to produce highly accurate MF chips is reported here for the first time.

Stroke frequency, associated factors, and clinical features in primary systemic vasculitis: a multicentric observational study.

Objectives: The cerebral vessels may be affected in primary systemic vasculitis (PSV), but little is known about cerebrovascular events (CVEs) in this population. This study aimed to determine the frequency of CVEs at the time of diagnosis of PSV, to identify factors associated with CVEs in PSV, and to explore features and outcomes of stroke in patients with PSV.

Methods: Data from adults newly diagnosed with PSV within the Diagnostic and Classification Criteria in VASculitis (DCVAS) study were analysed.

Patient Outcomes in Helicopter Emergency Medical Service Documentaries and on Air Ambulance Websites.

Background Helicopter emergency medical service (HEMS) documentaries attract millions of viewers, and publicly available patient stories on Air Ambulance websites are vital to raise awareness and funding for Air Ambulance charities in the United Kingdom (UK). Despite abundant research investigating how fictional programs and news outlets present patient health outcomes, there are no comprehensive studies that investigate how non-fictional HEMS documentaries or Air Ambulance websites present patient outcomes. The aim of this study is to capture the frequency of poor outcomes (mortality) in patients broadcasted on documentaries focusing on HEMS and the patient stories section of UK Air Ambulance websites.

Dissociation of Reliability, Heritability, and Predictivity in Coarse- and Fine-Scale Functional Connectomes during Development.

The functional connectome supports information transmission through the brain at various spatial scales, from exchange between broad cortical regions to finer-scale, vertex-wise connections that underlie specific information processing mechanisms. In adults, while both the coarse- and fine-scale functional connectomes predict cognition, the fine scale can predict up to twice the variance as the coarse-scale functional connectome. Yet, past brain-wide association studies, particularly using large developmental samples, focus on the coarse connectome to understand the neural underpinnings of individual differences in cognition.

FITM2 deficiency results in ER lipid accumulation, ER stress, reduced apolipoprotein B lipidation, and VLDL triglyceride secretion and in mouse liver.

Objectives: Triglyceride (TG) association with apolipoprotein B100 (apoB100) serves to form very low density lipoproteins (VLDL) in the liver. The repertoire of factors that facilitate this association is incompletely defined. FITM2, an integral endoplasmic reticulum (ER) protein, was originally discovered as a factor participating in cytoplasmic lipid droplets (LDs) in tissues that do not form VLDL.

Representational Dissimilarity of Faces and Places during a Working Memory Task is Associated with Subsequent Recognition Memory during Development.

Nearly 50 years of research has focused on faces as a special visual category, especially during development. Yet it remains unclear how spatial patterns of neural similarity of faces and places relate to how information processing supports subsequent recognition of items from these categories. The current study uses representational similarity analysis and functional imaging data from 9- and 10-year-old youth during an emotional n-back task from the Adolescent Brain and Cognitive Development Study 3.

A Scan of Pleiotropic Immune Mediated Disease Genes Identifies Novel Determinants of Baseline FVIII Inhibitor Status in Hemophilia-A.

Hemophilia-A (HA) is caused by heterogeneous loss-of-function factor (F)VIII gene ()-mutations and deficiencies in plasma-FVIII-activity that impair intrinsic-pathway-mediated coagulation-amplification. The standard-of-care for severe-HA-patients is regular infusions of therapeutic-FVIII-proteins (tFVIIIs) but ~30% develop neutralizing-tFVIII-antibodies called "FVIII-inhibitors (FEIs)" and become refractory. We used the PATH study and ImmunoChip to scan immune-mediated-disease (IMD)-genes for novel and/or replicated genomic-sequence-variations associated with baseline-FEI-status while accounting for non-independence of data due to genetic-relatedness and -mutational-heterogeneity.

The clinical presentation of avoidant restrictive food intake disorder in children and adolescents is largely independent of sex, autism spectrum disorder and anxiety traits.

Background: Avoidant restrictive food intake disorder (ARFID) is a new eating disorder with a heterogeneous clinical presentation. It is unclear which patient characteristics contribute to its heterogeneity.

Methods: To identify these patient characteristics, we performed symptom-level correlation and driver-level regression analyses in our cross-sectional study in up to 261 ARFID patients (51% female; median age = 12.

CD98hc is a target for brain delivery of biotherapeutics.

Brain exposure of systemically administered biotherapeutics is highly restricted by the blood-brain barrier (BBB). Here, we report the engineering and characterization of a BBB transport vehicle targeting the CD98 heavy chain (CD98hc or SLC3A2) of heterodimeric amino acid transporters (TV). The pharmacokinetic and biodistribution properties of a CD98hc antibody transport vehicle (ATV) are assessed in humanized CD98hc knock-in mice and cynomolgus monkeys.

Preferential lipolysis of DGAT1 over DGAT2 generated triacylglycerol in Huh7 hepatocytes.

Two distinct diacylglycerol acyltransferases (DGAT1 and DGAT2) catalyze the final committed step of triacylglycerol (TG) synthesis in hepatocytes. After its synthesis in the endoplasmic reticulum (ER) TG is either stored in cytosolic lipid droplets (LDs) or is assembled into very low-density lipoproteins in the ER lumen. TG stored in cytosolic LDs is hydrolyzed by adipose triglyceride lipase (ATGL) and the released fatty acids are converted to energy by oxidation in mitochondria.

Noninvasive Ventilation or CPAP for Postextubation Support in Small Infants.

Background: Infants with a high risk of extubation failure are often treated with noninvasive ventilation (NIV) or CPAP, but data on the role of these support modalities following extubation are sparse. This report describes our experience using NIV or CPAP to support infants following extubation in our pediatric ICUs (PICUs).

Methods: We performed a retrospective study of children < 10 kg receiving postextubation NIV or CPAP in our PICUs.

Classification and epidemiology of vasculitis: Emerging concepts.

The recent publication of the American College of Rheumatology (ACR)-European Alliance of Associations for Rheumatology (EULAR) classification criteria for large vessel vasculitis and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) has provided modern criteria for the classification of these conditions, which incorporate contemporary methods of investigation and diagnosis. Further validation is required in independent cohorts, especially from populations that were not well represented in the development cohort. Studies of the occurrence of large vessel vasculitis report that Takayasu arteritis is a rare disease in most populations, and giant cell arteritis is the most common vasculitis in older populations.

Incidence of primary large vessel vasculitis in Norfolk, UK from 2011 to 2020.

Objectives: To report the annual incidence of primary large vessel vasculitis (LVV) in the adult population of Norfolk County, UK, including giant cell arteritis (GCA) (in those ≥50 years) and Takayasu arteritis (TAK).

Methods: Individuals diagnosed by histology or imaging who lived in NR1-NR30 postcode districts were included. Validated criteria from 1990 and 2022 were applied for final classification.

Neural responses to reward valence and magnitude from pre- to early adolescence.

Background: Neural activation during reward processing is thought to underlie critical behavioral changes that take place during the transition to adolescence (e.g., learning, risk-taking).

Genetic and Environmental Contributions to Subcortical Gray Matter Microstructure and Volume in the Developing Brain.

Using baseline (ages 9-10) and two-year follow-up (ages 11-12) data from monozygotic and dizygotic twins enrolled in the longitudinal Adolescent Brain Cognitive Development Study, we investigated the genetic and environmental contributions to microstructure and volume of nine subcortical gray matter regions. Microstructure was assessed using diffusion MRI data analyzed using restriction spectrum imaging (RSI) and diffusion tensor imaging (DTI) models. The highest heritability estimates (estimate [95% confidence interval]) for microstructure were found using the RSI model in the pallidum (baseline: 0.