Micronuclear collapse from oxidative damage.

Chromosome-containing micronuclei are a hallmark of aggressive cancers. Micronuclei frequently undergo irreversible collapse, exposing their enclosed chromatin to the cytosol. Micronuclear rupture catalyzes chromosomal rearrangements, epigenetic abnormalities, and inflammation, yet mechanisms safeguarding micronuclear integrity are poorly understood.

Effectiveness and cost-effectiveness of a community intervention in enhancing access to care and improving clinical outcomes for depression: a protocol for a cluster randomised controlled trial in India.

Background: Although depression is the leading cause of disability worldwide, treatment coverage for the condition is inadequate. Supply-side barriers (e.g.

Modulation of prion protein expression through cryptic splice site manipulation.

Lowering expression of prion protein (PrP) is a well-validated therapeutic strategy in prion disease, but additional modalities are urgently needed. In other diseases, small molecules have proven capable of modulating pre-mRNA splicing, sometimes by forcing inclusion of cryptic exons that reduce gene expression. Here, we characterize a cryptic exon located in human PRNP's sole intron and evaluate its potential to reduce PrP expression through incorporation into the 5' untranslated region.

Differences in 5'untranslated regions highlight the importance of translational regulation of dosage sensitive genes.

Background: Untranslated regions (UTRs) are important mediators of post-transcriptional regulation. The length of UTRs and the composition of regulatory elements within them are known to vary substantially across genes, but little is known about the reasons for this variation in humans. Here, we set out to determine whether this variation, specifically in 5'UTRs, correlates with gene dosage sensitivity.

variants in the non-coding spliceosomal snRNA gene are a frequent cause of syndromic neurodevelopmental disorders.

Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes. Increasingly, large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here, we identify the non-coding RNA as a novel syndromic NDD gene.

Modulation of prion protein expression through cryptic splice site manipulation.

Lowering expression of prion protein (PrP) is a well-validated therapeutic strategy in prion disease, but additional modalities are urgently needed. In other diseases, small molecules have proven capable of modulating pre-mRNA splicing, sometimes by forcing inclusion of cryptic exons that reduce gene expression. Here, we characterize a cryptic exon located in human 's sole intron and evaluate its potential to reduce PrP expression through incorporation into the 5' untranslated region (5'UTR).

Investigating insomnia in United States deployed military forces: A topic modeling approach.

Study Objectives: This retrospective study analyzed free-text clinical notes from medical encounters for insomnia among a sample of deployed US military personnel. Topic modeling, a natural language processing technique, was used to identify thematic patterns in the clinical notes that were potentially related to insomnia diagnosis.

Methods: Clinical notes of patient clinical encounters coded for insomnia from the US Department of Defense Military Health System Theater Medical Data Store were analyzed.

Acceptability and feasibility of assisted telepsychiatry in routine healthcare settings in India: a qualitative study.

Technology-enabled interventions are often recommended to overcome geographical barriers to access and inequitable distribution of mental healthcare workers. The aim of this study was to examine the acceptability and feasibility of an assisted telepsychiatry model implemented in primary care settings in India. In-depth interviews were conducted with patients who received telepsychiatry consultations.

Experiences of a mobile phone delivered brief intervention for hazardous drinking: A qualitative study nested in the AMBIT trial from Goa, India.

Background: This study explores the experiences of participants receiving a mobile-based brief intervention (BI) for hazardous drinking in India, to determine characteristics that influenced engagement and examine perceived reasons for change in alcohol consumption.

Methods: Semi-structured interviews were conducted with 10 adult hazardous drinkers who received a mobile-based BI in the intervention arm of a pilot randomised control trial. Data were coded through an iterative process and analysed using thematic analysis.

Cellular Heterogeneity of Activated Primary Human Macrophages and Associated Drug-Gene Networks: From Biology to Precision Therapeutics.

Background: Interferon-γ (IFNγ) signaling plays a complex role in atherogenesis. IFNγ stimulation of macrophages permits in vitro exploration of proinflammatory mechanisms and the development of novel immune therapies. We hypothesized that the study of macrophage subpopulations could lead to anti-inflammatory interventions.

Systematic identification of disease-causing promoter and untranslated region variants in 8,040 undiagnosed individuals with rare disease.

Background: Both promoters and untranslated regions (UTRs) have critical regulatory roles, yet variants in these regions are largely excluded from clinical genetic testing due to difficulty in interpreting pathogenicity. The extent to which these regions may harbour diagnoses for individuals with rare disease is currently unknown.

Methods: We present a framework for the identification and annotation of potentially deleterious proximal promoter and UTR variants in known dominant disease genes.

Tolerance to aerial exposure influences distributional patterns in multi-species intertidal seagrass meadows.

Multi-specific seagrass meadow assemblages dominate most tropical intertidal regions but the relative role of environmental stress in determining distribution patterns is still uncertain. Here we combine observational and experimental approaches to examine aerial exposure as a factor driving species occurrence patterns in intertidal meadows of the Andaman archipelago, where up to 6 seagrass species co-occur. In the studied meadow, patterns of exposure did not map onto distance from the coast, instead creating a patchy matrix of exposure, based on fine-scale bathymetric differences.

Smartphone Bolus Feature Increases Number of Insulin Boluses in People With Low Bolus Frequency.

Background: The t:connect mobile app from Tandem Diabetes Care recently added a feature to allow t:slim X2 insulin pump users to initiate an insulin bolus from their personal smartphone. User experience and user interface considerations prioritized safety and ease of use, and we examined whether the smartphone bolus feature changed bolus behavior in individuals who bolused less than three times/day.

Methods: We performed a retrospective analysis of t:slim X2 insulin pump users in the United States who had remotely updated their insulin pump software to be compatible with the smartphone bolus version of the app and who gave less than three boluses per day prior to the smartphone bolus update.

Ecobiology and distribution of Streptomyces species from distinctive metal polluted sediment of tropical estuary, Northwest coast of India.

The present study aims to isolate diverse actinomycetes communities from the estuarine sediments of Patalganga located at Northwest coast of India. Total 40 actinomycetes were isolated from 24 sediment samples by dilution plating on six different isolation media. Among them, morphologically 18 distinct selected isolates of actinomycetes were verified by 16S rRNA gene sequencing and identified as Streptomyces spp.

Sustaining youth physical activity in times of challenge and change: lessons from COVID-19.

Physical activity (PA) is recognized as essential for positive physical and mental well-being in young people. However, participation in PA is known to decline as adolescents emerge into adulthood under the influence of complex social and structural factors. Globally, COVID-19 restrictions resulted in changes to PA and PA participation levels in youth populations, providing a unique opportunity for gaining insight into PA barriers and enablers in circumstances of challenge, limitation and change.

Research Letter: Prevalence of Spine Injuries Among US Military Personnel With Combat-Related Concussion.

Objective: To describe the prevalence of spine injuries among US service members with combat-related concussion.

Design And Participants: A retrospective review of medical records for US service members injured during combat operations in Iraq and Afghanistan between 2002 and 2020. The study sample included 27 897 service members categorized into 3 groups: concussion with loss of consciousness (LOC, n = 4631), concussion non-LOC ( n = 5533), and non-concussion ( n = 17 333).

Identifying conservation priorities for a widespread dugong population in the Red Sea: Megaherbivore grazing patterns inform management planning.

Extensive home ranges of marine megafauna present a challenge for systematic conservation planning because they exceed spatial scales of conventional management. For elusive species like dugongs, their management is additionally hampered by a paucity of basic distributional information across much of their range. The Red Sea is home to a wide-spread, globally important but data-poor population of dugongs.

Gut microbiota and host genetics modulate the effect of diverse diet patterns on metabolic health.

Metabolic diseases are major public health issues worldwide and are responsible for disproportionately higher healthcare costs and increased complications of many diseases including SARS-CoV-2 infection. The Western Diet (WD) specifically is believed to be a major contributor to the global metabolic disease epidemic. In contrast, the Mediterranean diet (MeD), Ketogenic diet (KD), and Japanese diet (JD) are often considered beneficial for metabolic health.

Culture of Healthy Eating and Food Environments, Policies, and Practices in Regional New Zealand Schools.

The school food environment plays an important role in shaping students' dietary choices, which often influence future dietary behaviours. We surveyed primary and secondary schools in Hawke's Bay, New Zealand, to measure the comprehensiveness and strength of food policies, describe the culture of food provision, and identify barriers to improving school food environments. Fifty-one schools were included in the final analysis, with 58.