The α-globin super-enhancer acts in an orientation-dependent manner.

Individual enhancers are defined as short genomic regulatory elements, bound by transcription factors, and able to activate cell-specific gene expression at a distance, in an orientation-independent manner. Within mammalian genomes, enhancer-like elements may be found individually or within clusters referred to as locus control regions or super-enhancers (SEs). While these behave similarly to individual enhancers with respect to cell specificity, distribution and distance, their orientation-dependence has not been formally tested.

Diet Quality, Metabolic Syndrome, and Nativity Status: Elucidating Metabolic Advantage and Disadvantage Among Non-US-Native and US-Native Populations Using NHANES Data (2013-2018).

Background/objectives: Nutrient-poor diet quality is a major driver of the global burden of metabolic syndrome (MetS). The US ranks among the lowest in diet quality and has the highest rate of immigration, which may present unique challenges for non-US-native populations who experience changes in access to health-promoting resources. This study examined associations among MetS, nativity status, diet quality, and interaction effects of race-ethnicity among Hispanic, Asian, Black, and White US-native and non-US-native adults.

From Breaking Bad to Breaking Bonds-Mass Spectrometry in the Classroom.

We describe a workshop that prompts chemistry students in the final 2 years of secondary school to apply their understanding of modern analytical chemistry techniques to a 'real world' example. The scenario used is that of a forensic science laboratory that has been asked to determine the structure of an illicit compound, Revisomed (methamphetamine) being sold as a revision aid, and seized by police. Over the course of an hour, the students use a combination of infrared (IR) spectroscopy, liquid chromatography (LC), high-resolution mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy data to determine the structure of Revisomed from first principles.

Simulation of clinical trials of oral treprostinil in pulmonary arterial hypertension using a virtual population.

Challenges in drug development for rare diseases such as pulmonary arterial hypertension can be addressed through the use of mathematical modeling. In this study, a quantitative systems pharmacology model of pulmonary arterial hypertension pathophysiology and pharmacology was used to predict changes in pulmonary vascular resistance and six-minute walk distance in the context of oral treprostinil clinical studies. We generated a virtual population that spanned the range of clinical observations and then calibrated virtual patient-specific weights to match clinical trials.

Dysregulation of the NLRP3 Inflammasome and Promotion of Disease by IL-1β in a Murine Model of Sandhoff Disease.

Sandhoff disease (SD) is a progressive neurodegenerative lysosomal storage disorder characterized by GM2 ganglioside accumulation as a result of mutations in the gene, which encodes the β-subunit of the enzyme β-hexosaminidase. Lysosomal storage of GM2 triggers inflammation in the CNS and periphery. The NLRP3 inflammasome is an important coordinator of pro-inflammatory responses, and we have investigated its regulation in murine SD.

Multiplicity of type 6 secretion system toxins limits the evolution of resistance.

The bacterial type 6 secretion system (T6SS) is a toxin-injecting nanoweapon that mediates competition in plant- and animal-associated microbial communities. Bacteria can evolve de novo resistance against T6SS attacks, but resistance is far from universal in natural communities, suggesting key features of T6SS weaponry may act to limit its evolution. Here, we combine ecoevolutionary modeling and experimental evolution to examine how toxin type and multiplicity in attackers shape resistance evolution in susceptible competitors.

A Global Collaborative Comparison of SARS-CoV-2 Antigenicity Across 15 Laboratories.

Setting up a global SARS-CoV-2 surveillance system requires an understanding of how virus isolation and propagation practices, use of animal or human sera, and different neutralisation assay platforms influence assessment of SARS-CoV-2 antigenicity. In this study, with the contribution of 15 independent laboratories across all WHO regions, we carried out a controlled analysis of neutralisation assay platforms using the first WHO International Standard for antibodies to SARS-CoV-2 variants of concern (source: NIBSC). Live virus isolates (source: WHO BioHub or individual labs) or spike plasmids (individual labs) for pseudovirus production were used to perform neutralisation assays using the same serum panels.

Anti-gene oligonucleotide clamps invade dsDNA and downregulate expression.

Anti-gene oligonucleotides belong to a group of therapeutic compounds, which, in contrast to antisense oligonucleotides, bind to DNA. Clamp anti-gene oligonucleotides bind through a double-stranded invasion mechanism. With two arms connected by a linker, they hybridize to one of the DNA strands forming Watson-Crick and Hoogsteen hydrogen bonds.

Repair of Microperforate Hymen.

Objective: Subocclusive variants of the hymen are a group of hymenal anomalies that result due to a failure of canalization of the urogenital sinus. One of these variations is the microperforate hymen, for which accurate incidence is unknown. Microperforate hymen is a non-obstructing variation that allows for menstrual egress and often patients present due to inability to use a tampon.

Molecular and spatial analysis of tertiary lymphoid structures in Sjogren's syndrome.

Tertiary lymphoid structures play important roles in autoimmune and non-autoimmune conditions. While many of the molecular mechanisms involved in tertiary lymphoid structure formation have been identified, the cellular sources and temporal and spatial relationship remain unknown. Here we use combine single-cell RNA-sequencing, spatial transcriptomics and proteomics of minor salivary glands of patients with Sjogren's disease and Sicca Syndrome, with ex-vivo functional studies to construct a cellular and spatial map of key components involved in the formation and function of tertiary lymphoid structures.

Implementation of Billing for Patient Portal Messages as E-visits in a Large Integrated Health System.

Background: Patient-provider communication through the patient portal has markedly increased in recent years. Some health care facilities implemented programs to enable providers to bill for responding to patient-initiated messages that require substantive medical decision making through an e-visit.

Objective: To evaluate the effect of billing eligible patient-initiated portal messages as e-visits using a mixed-methods approach.

Mapping quantitative trait loci regions associated with Marek's disease on chicken autosomes by means of selective DNA pooling.

Marek's Disease (MD), which can result in neurological damage and tumour formation, has large effects on the economy and animal welfare of the poultry industry worldwide. Previously, we mapped autosomal MD QTL regions (QTLRs) by individual genotyping of an F population from a full-sib advanced intercross line. We further mapped MD QTLRs on the chicken Z chromosome (GGZ) using the same F population, and by selective DNA pooling (SDP) of 8 elite egg production lines.

The ADHD Assessment Quality Assurance Standard for Children and Teenagers (CAAQAS).

Around 5% of the children and teenagers worldwide are affected by Attention-Deficit/Hyperactivity Disorder [ADHD], making it a major public health concern. Recently, demand for assessments has substantially increased, putting strain on healthcare and waiting lists. There is concern that pressure to clear service bottlenecks is leading to variable quality and reliability of ADHD assessments in this population.

Faster and better than a physician?: Assessing diagnostic proficiency of ChatGPT in misdiagnosed individuals with neuromyelitis optica spectrum disorder.

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a commonly misdiagnosed condition. Driven by cost-consciousness and technological fluency, distinct generations may gravitate towards healthcare alternatives, including artificial intelligence (AI) models, such as ChatGPT (Generative Pre-trained Transformer). Our objective was to evaluate the speed and accuracy of ChatGPT-3.

Remineralisation of enamel erosive lesions by daily-use fluoride treatments: network meta-analysis of an in situ study set.

Objectives: Daily-use fluoride products are first-line protection against enamel wear from dietary-acid exposure (DAE). This study aimed to understand effects of fluoride concentration, fluoride salt, product form and ingredients in daily-use products on remineralisation and demineralisation, via network meta-analysis (NMA) of 14 studies using one well-established in-situ model. Remineralisation (surface-microhardness recovery, SHMR) after treatment, and protection against subsequent demineralisation (acid-resistance ratio, ARR) were measured.

Genetic Variants Associated With Preeclampsia and Maternal Serum sFLT1 Levels.

Background: Elevated maternal serum sFLT1 (soluble fms-like tyrosine kinase 1) has a key role in the pathophysiology of preeclampsia. We sought to determine the relationship between the maternal and fetal genome and maternal levels of sFLT1 at 12, 20, 28, and 36 weeks of gestational age (wkGA).

Methods: We studied a prospective cohort of nulliparous women (3968 mother-child pairs).

Operationalizing the New Global Definition of ARDS: A Retrospective Cohort Study From South Africa.

Background: A proposed new global definition of ARDS seeks to update the Berlin definition and account for nonintubated ARDS and ARDS diagnoses in resource-variable settings.

Research Question: How do ARDS epidemiologic characteristics change with operationalizing the new global definition of ARDS in a resource-limited setting?

Study Design And Methods: We performed a real-use retrospective cohort study among adult patients meeting criteria for the Berlin definition of ARDS or the global definition of ARDS at ICU admission in two public hospitals in the KwaZulu-Natal Department of Health, South Africa, from January 2017 through June 2022.

Results: Among 5,760 adults (aged ≥ 18 years) admitted to the ICU, 2,027 patients (35.

eEF2K regulates pain through translational control of BDNF.

mRNA translation is integral to pain, yet the key regulatory factors and their target mRNAs are unclear. Here, we uncover a mechanism that bridges noxious insults to multiple phases of translational control in murine sensory neurons. We find that a painful cue triggers repression of peptide chain elongation through activation of elongation factor 2 kinase (eEF2K).

Imaging NRF2 activation in non-small cell lung cancer with positron emission tomography.

Mutations in the NRF2-KEAP1 pathway are common in non-small cell lung cancer (NSCLC) and confer broad-spectrum therapeutic resistance, leading to poor outcomes. Currently, there is no means to non-invasively identify NRF2 activation in living subjects. Here, we show that positron emission tomography imaging with the system x radiotracer, [F]FSPG, provides a sensitive and specific marker of NRF2 activation in orthotopic, patient-derived, and genetically engineered mouse models of NSCLC.

A neural network to create super-resolution MR from multiple 2D brain scans of pediatric patients.

Background: High-resolution (HR) 3D MR images provide detailed soft-tissue information that is useful in assessing long-term side-effects after treatment in childhood cancer survivors, such as morphological changes in brain structures. However, these images require long acquisition times, so routinely acquired follow-up images after treatment often consist of 2D low-resolution (LR) images (with thick slices in multiple planes).

Purpose: In this work, we present a super-resolution convolutional neural network, based on previous single-image MRI super-resolution work, that can reconstruct a HR image from 2D LR slices in multiple planes in order to facilitate the extraction of structural biomarkers from routine scans.