IL-33 is associated with alveolar dysfunction in patients with viral lower respiratory tract disease.

Interleukin (IL)-33 is released following tissue damage, causing airway inflammation and remodelling via reduced IL-33 (IL-33)/serum stimulation-2 (ST2) and oxidised IL-33 (IL-33)/receptor for advanced glycation end products (RAGE)/epidermal growth factor receptor (EGFR) pathways. This study aimed to identify associations of IL-33 with clinical outcomes and pathological mechanisms during viral lower respiratory tract disease (LRTD). Ultra-sensitive immunoassays were developed to measure IL-33, IL-33 and IL-33/sST2 complexes in samples from patients hospitalised with COVID-19.

Evaluating the impact of redox potential on the growth capacity of anaerobic gut fungi.

Anaerobic gut fungi (AGF, ) inhabit the alimentary tract of herbivores. Although strict anaerobes, studies have suggested their capacity to retain viability after various durations of air exposure. It is currently unclear whether AGF can actively grow, and not merely survive, in redox potentials (E) higher than those encountered in the herbivorous gut.

Neurodevelopmental Disorder Caused by Deletion of , a lncRNA Gene.

encodes a human long noncoding RNA (lncRNA) adjacent to , a coding gene in which de novo loss-of-function variants cause developmental and epileptic encephalopathy. Here, we report our findings in three unrelated children with a syndromic, early-onset neurodevelopmental disorder, each of whom had a de novo deletion in the locus. The children had severe encephalopathy, shared facial dysmorphisms, cortical atrophy, and cerebral hypomyelination - a phenotype that is distinct from the phenotypes of patients with haploinsufficiency.

A cell type-aware framework for nominating non-coding variants in Mendelian regulatory disorders.

Unsolved Mendelian cases often lack obvious pathogenic coding variants, suggesting potential non-coding etiologies. Here, we present a single cell multi-omic framework integrating embryonic mouse chromatin accessibility, histone modification, and gene expression assays to discover cranial motor neuron (cMN) cis-regulatory elements and subsequently nominate candidate non-coding variants in the congenital cranial dysinnervation disorders (CCDDs), a set of Mendelian disorders altering cMN development. We generate single cell epigenomic profiles for ~86,000 cMNs and related cell types, identifying ~250,000 accessible regulatory elements with cognate gene predictions for ~145,000 putative enhancers.

Cruel optimism, affective governmentality and frontline poverty governance: 'You can promise the world'.

Cruel Optimism' (Berlant, 2011) sustains neoliberalism by promising freedom and autonomy through adherence to and performance of competitive behaviours. As Brown (2003) observes, neoliberalism is a discourse which operates, not through repression or restriction, but through promising self-fulfilment and happiness. The role of emotion-management in poverty governance has been widely acknowledged.

Dynamic changes in insulin-like growth factor binding protein expression occur between embryonic and early post-hatch development in broiler chickens.

Somatotropic gene expression has been altered by genetic selection, and developmental changes in insulin-like growth factor (IGF) and IGF binding protein (IGFBP) expression may contribute to rapid growth and muscle accretion in commercial broilers. The objective of this study was to evaluate changes in somatotropic axis activity between embryonic day (e) 12 and post-hatch day (d) 21. Liver and breast muscle (pectoralis major) were collected to measure gene expression, and blood was collected post-hatch to measure circulating IGFs.

Effects of night-float shifts on cognitive function among radiology residents.

Background: Many radiology programs utilize a night-float system to mitigate the effects of fatigue, improve patient care, and provide faster report turnaround times. Prior studies have demonstrated an increase in discrepancy rates during night-float shifts.

Objectives: This study was performed to examine the effects of night-float shift work on radiology resident cognition.

Facilitators and barriers to the delivery of the PARAMEDIC2 trial.

Background: PARAMEDIC2 was a medicines trial comparing adrenaline with placebo in out-of-hospital cardiac arrest (OHCA). At the time, United Kingdom (UK) Emergency Medical Systems (EMS) were inexperienced in delivering such research.

Aim: To identify barriers and facilitators to delivery of the PARAMEDIC2 (Adrenaline) trial by five UK NHS EMS.

Nutrition: Chronic Disease Management.

Dietary modifications can help to prevent and manage many chronic diseases. The Mediterranean and Dietary Approaches to Stop Hypertension (DASH) diets emphasize consumption of fruits and vegetables while reducing intake of red meat. These diets are supported by well-established evidence for patients with cardiovascular disease and hypertension, respectively.

Nutrition: Micronutrients.

Micronutrients are nutrients the body needs in small quantities, such as vitamins and minerals. Micronutrient deficiencies can occur when an individual is restricting calorie intake for weight loss or management, not consuming an adequate amount of food to meet energy requirements due to poor appetite or illness, eliminating one or more food groups from the diet on a regular basis, or consuming a diet low in micronutrient-rich foods despite adequate or excessive energy intake. Patient groups at risk include older adults, pregnant patients, patients with alcohol use disorder, patients with vegetarian or vegan diets, and patients with increased requirements secondary to medical conditions or long-term drug use that alters nutrient absorption, metabolism, or excretion.

Nutrition: Macronutrients.

Macronutrients are nutrients the body needs in large quantities, such as fats, carbohydrates, fiber, protein, and water. The exact quantity of macronutrients needed for an individual depends on multiple factors such as height, weight, sex, physical activity level, and medical conditions. For adequate intake, the () recommend an overall healthy eating pattern rather than specific macronutrient amounts.

Expanding the genetics and phenotypes of ocular congenital cranial dysinnervation disorders.

Purpose: To identify genetic etiologies and genotype/phenotype associations for unsolved ocular congenital cranial dysinnervation disorders (oCCDDs).

Methods: We coupled phenotyping with exome or genome sequencing of 467 pedigrees with genetically unsolved oCCDDs, integrating analyses of pedigrees, human and animal model phenotypes, and variants to identify rare candidate single nucleotide variants, insertion/deletions, and structural variants disrupting protein-coding regions. Prioritized variants were classified for pathogenicity and evaluated for genotype/phenotype correlations.

Exome copy number variant detection, analysis, and classification in a large cohort of families with undiagnosed rare genetic disease.

Copy number variants (CNVs) are significant contributors to the pathogenicity of rare genetic diseases and, with new innovative methods, can now reliably be identified from exome sequencing. Challenges still remain in accurate classification of CNV pathogenicity. CNV calling using GATK-gCNV was performed on exomes from a cohort of 6,633 families (15,759 individuals) with heterogeneous phenotypes and variable prior genetic testing collected at the Broad Institute Center for Mendelian Genomics of the Genomics Research to Elucidate the Genetics of Rare Diseases consortium and analyzed using the seqr platform.

The key characteristics of cardiotoxicity for the pervasive pollutant phenanthrene.

The key characteristic (KCs) framework has been used previously to assess the carcinogenicity and cardiotoxicity of various chemical and pharmacological agents. Here, the 12 KCs of cardiotoxicity are used to evaluate the previously reported cardiotoxicity of phenanthrene (Phe), a tricyclic polycyclic aromatic hydrocarbon (PAH), and major component of fossil fuel-derived air pollution. Phe is a semi-volatile pollutant existing in both the gas phase and particle phase through adsorption onto or into particulate matter (PM).

Neurodevelopmental disorders associated variants in disrupt the activity of the ADAT2/ADAT3 tRNA deaminase complex and impair neuronal migration.

The ADAT2/ADAT3 complex catalyzes the adenosine to inosine modification at the wobble position of eukaryotic tRNAs. Mutations in , the catalytically inactive subunit of the ADAT2/ADAT3 complex, have been identified in patients presenting with severe neurodevelopmental disorders (NDDs). Yet, the physiological function of ADAT2/ADAT3 complex during brain development remains totally unknown.

Compatibility versus reaction diffusion: Factors that determine the heterogeneity of polymerized adhesive networks.

Objectives: Heterogeneity and phase separation during network polymerization is a major issue contributing to the failure of dental adhesives. This study investigates how the ratio of hydrophobic crosslinkers to hydrophilic comonomer (C/H ratio), as well as cosolvent fraction (ethanol/water) influences the degree of heterogeneity and proclivity for phase separation in a series of model adhesive formulations.

Methods: Twelve formulations were investigated, with 4 different C/H ratios (7:1, 2.

Digenic inheritance involving a muscle-specific protein kinase and the giant titin protein causes a skeletal muscle myopathy.

In digenic inheritance, pathogenic variants in two genes must be inherited together to cause disease. Only very few examples of digenic inheritance have been described in the neuromuscular disease field. Here we show that predicted deleterious variants in SRPK3, encoding the X-linked serine/argenine protein kinase 3, lead to a progressive early onset skeletal muscle myopathy only when in combination with heterozygous variants in the TTN gene.

Unique Capabilities of Genome Sequencing for Rare Disease Diagnosis.

Background: Causal variants underlying rare disorders may remain elusive even after expansive gene panels or exome sequencing (ES). Clinicians and researchers may then turn to genome sequencing (GS), though the added value of this technique and its optimal use remain poorly defined. We therefore investigated the advantages of GS within a phenotypically diverse cohort.