Cytosolic DNA composition is determined by genomic instability mechanism and regulates dendritic cell-mediated anti-tumor immunity.

Patients with colorectal cancers (CRCs) that have microsatellite instability (MSI) (MSI CRCs) face a better prognosis than those with the more common chromosomal instability (CIN) subtype (CIN CRCs) due to improved T cell-mediated anti-tumor immune responses. Previous investigations identified the cytosolic DNA (cyDNA) sensor STING as necessary for chemokine-mediated T cell recruitment in MSI CRCs. Here, we find that cyDNA from MSI CRC cells is inherently more capable of inducing STING activation and improves cytotoxic T cell activation by dendritic cells (DCs).

Exploring the Effect of Sampling Frequency on Real-World Mobility, Sedentary Behaviour, Physical Activity and Sleep Outcomes Measured with Wearable Devices in Rheumatoid Arthritis: Feasibility, Usability and Practical Considerations.

Modern treat-to-target management of rheumatoid arthritis (RA) involves titration of drug therapy to achieve remission, requiring close monitoring of disease activity through frequent clinical assessments. Accelerometry offers a novel method for continuous remote monitoring of RA activity by capturing fluctuations in mobility, sedentary behaviours, physical activity and sleep patterns over prolonged periods without the expense, inconvenience and environmental impact of extra hospital visits. We aimed to (a) assess the feasibility, usability and acceptability of wearable devices in patients with active RA; (b) investigate the multivariate relationships within the dataset; and (c) explore the robustness of accelerometry outcomes to downsampling to facilitate future prolonged monitoring.

Computational design of highly signalling-active membrane receptors through solvent-mediated allosteric networks.

Protein catalysis and allostery require the atomic-level orchestration and motion of residues and ligand, solvent and protein effector molecules. However, the ability to design protein activity through precise protein-solvent cooperative interactions has not yet been demonstrated. Here we report the design of 14 membrane receptors that catalyse G protein nucleotide exchange through diverse engineered allosteric pathways mediated by cooperative networks of intraprotein, protein-ligand and -solvent molecule interactions.

Exploring Context Allows Us to Better Understand Physical Activity in People with and Without Parkinson's Who Have Fallen: A Mixed Methods Study.

Falls are a frequent and serious problem for older adults, especially for those living with Parkinson's. The relationship between falls and physical activity is complex, and people often restrict activity following a fall. Exercise is an important aspect of reducing further risk of a fall and a key component of the management of Parkinson's.

Polycomb-associated and Trithorax-associated developmental conditions-phenotypic convergence and heterogeneity.

Polycomb group (PcG) and Trithorax group (TrxG) complexes represent two major components of the epigenetic machinery. This study aimed to delineate phenotypic similarities and differences across developmental conditions arising from rare variants in PcG and TrxG genes, using data-driven approaches. 462 patients with a PcG or TrxG-associated condition were identified in the DECIPHER dataset.

Conference report of the 2024 Antimicrobial Resistance Meeting.

The Antimicrobial Resistance - Genomes, Big Data and Emerging Technologies Conference explored key topics including measuring the burden of AMR, global public health pathogen genomics infrastructure and surveillance, translation and implementation of genomics for AMR control, use of techniques such as wastewater surveillance, mathematical and statistical modelling, and Artificial Intelligence (AI) to aid understanding of AMR. This report describes research presented during plenary sessions and discussions, keynote presentations and posters.

Differential encoding of odor and place in mouse piriform and entorhinal cortex.

The integration of olfactory and spatial information is critical for guiding animal behavior. The lateral entorhinal cortex (LEC) is reciprocally interconnected with cortical areas for olfaction and the hippocampus and thus ideally positioned to encode odor-place associations. Here, we used mini-endoscopes to record neural activity in the mouse piriform cortex (PCx) and LEC.

Effectiveness of sulfadoxine-pyrimethamine plus amodiaquine and dihydroartemisinin-piperaquine for seasonal malaria chemoprevention in Uganda: a three-arm, open-label, non-inferiority and superiority, cluster-randomised, controlled trial.

Background: Seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine combined with amodiaquine (SPAQ) effectively protects eligible children from malaria in areas of high and seasonal transmission. However, concerns about parasite resistance to sulfadoxine-pyrimethamine in East and Southern Africa necessitate evaluating alternative drug regimens. This study assessed the effectiveness of SPAQ and dihydroartemisinin-piperaquine for SMC in Uganda.

Expediated modeling of burn events results (EMBER): A screening-level dataset of 2023 ozone fire impacts in the US.

The Expedited Modeling of Burn Events Results (EMBER) dataset consists of 36-km grid-spacing Community Multiscale Air Quality (CMAQ) photochemical modeling for the summer of 2023. For emissions, these simulations utilized representative monthly and day-of-week anthropogenic emissions from a recent year and preliminary day-specific 2023 fire emissions derived using BlueSky pipeline. The base model run simulated ozone concentrations across the contiguous US during Apr 11-Sep 29, 2023.

"Consider-the-Opposite" Debiasing to Improve Self-Assessment Accuracy in Anesthesiology Trainees: A Prospective Pretest-Posttest Study.

Accurate self-assessments enhance learning and patient care, yet resident physicians self-assess poorly. We therefore tested the effects of a consider-the-opposite (CTO) cognitive debiasing technique on self-assessment accuracy among anesthesiology residents. Trainees self-assessed their technical skills and communication/leadership abilities, then completed a CTO intervention before repeating self-assessments.

Nuclear and mitochondrial genome assemblies for the endangered wood-decaying fungus Somion occarium.

Somion occarium is a wood-decaying bracket fungus belonging to an order known to be rich in useful chemical compounds. Despite its widespread distribution, S. occarium has been assessed as endangered on at least one national Red List, presumably due to loss of old-growth forest habitat.

Baseline Estimates for Companion Animals Living in Households in Hawai'i: Associated Socio-Demographic, and Select Health Variables, as Measured by a Household Survey.

Information on companion animals in Hawai'i is lacking. The Hawai'i Department of Health's Hawai'i Health Survey, collected data on adults and households by telephone interview. National estimates of companion animals range from 50-67%.

TAK-994 Mechanistic Investigation into Drug-Induced Liver Injury.

The frequency of drug-induced liver injury (DILI) in clinical trials remains a challenge for drug developers despite advances in human hepatotoxicity models and improvements in reducing liver-related attrition in preclinical species. TAK-994, an oral orexin receptor 2 agonist, was withdrawn from phase II clinical trials due to the appearance of severe DILI. Here, we investigate the likely mechanism of TAK-994 DILI in hepatic cell culture systems examined cytotoxicity, mitochondrial toxicity, impact on drug transporter proteins, and covalent binding.

Reconsidering remission in recurrent late-life depression: clinical presentation and phenotypic predictors of relapse following successful antidepressant treatment.

Background: Late-life depression (LLD) is characterized by repeated recurrent depressive episodes even with maintenance treatment. It is unclear what clinical and cognitive phenotypic characteristics present during remission predict future recurrence.

Methods: Participants (135 with remitted LLD and 69 comparison subjects across three institutions) completed baseline phenotyping, including psychiatric, medical, and social history, psychiatric symptom and personality trait assessment, and neuropsychological testing.

Ultra-fast single-crystal CVD diamonds in the particle time-of-flight (PTOF) detector for low yield burn-history measurements on the NIF (invited).

The Particle Time of Flight (PTOF) diagnostic is a chemical vapor deposition diamond-based detector and is the only diagnostic for measuring nuclear bang times of low yield (<1013) shots on the National Ignition Facility. Recently, a comprehensive study of detector impulse responses revealed certain detectors with very fast and consistent impulse responses with a rise time of <50 ps, enabling low yield burn history measurements. At the current standoff of 50 cm, this measurement is possible with fast 14 MeV neutrons from deuterium-tritium (DT) fusion plasmas.

The challenges experienced by collegiate athlete cancer survivors.

Purpose: The growing number of athletes diagnosed with cancer requires a better understanding of their background, experiences, and specific goals to provide personalized care. Therefore, the purpose of this study was to explore the lived experiences of collegiate athletes in the United States diagnosed with cancer, reflecting on various barriers and challenges because of their cancer diagnosis, as they relate to their athletic participation and educational experiences.

Methods: This qualitative study used a phenomenological approach to study the nature and states of lived experiences in collegiate athlete cancer survivors diagnosed with cancer between the ages of 10 and 39 years old.

Pediatric Transplant and Cellular Therapy Consortium RESILIENT Conference on Pediatric Chronic Graft-Versus-Host Disease Survivorship After Hematopoietic Cell Transplantation: Part IV. Patient Important Outcomes.

Chronic graft-versus-host disease (cGVHD) occurs in approximately 1 in 5 pediatric allogeneic HCT patients and is a leading cause of late morbidity and mortality. Late effects of hematopoietic cell transplantation (HCT) may lead to long-term chronic health conditions and shortened life expectancy. In addition to direct physiologic challenges from cGVHD and other late effects, numerous patient-important outcomes impact the quality of life (QOL) of patients and their families.

Prevalence and Economic Burden of Osteoarthritis and Rheumatoid Arthritis in the Medically Underserved Rio Grande Valley: A Retrospective Longitudinal Analysis.

Introduction Osteoarthritis and rheumatoid arthritis, two of the most common forms of arthritis worldwide, are chronic diseases affecting the joints. The Rio Grande Valley is characterized by an abundance of health disparities, with previous studies showing increased rates of multiple diseases and disorders in this region. This study aimed to determine both the prevalence and the risk-adjusted average cost of osteoarthritis and rheumatoid arthritis in the Rio Grande Valley and to compare them with the national average.

Impact of Social Vulnerability, Race, and Urbanicity on Surgical Timing for Patients With Craniosynostosis.

Prior studies have linked the timing of craniosynostosis surgeries to several postoperative outcomes. However, less is known regarding the influence of sociodemographic factors on surgical timing for this population. This study investigates the influence of social vulnerability index (SVI), race, and urbanicity on the timing of craniosynostosis surgery.

Living with pain and Parkinson's developing an understanding of the impact, trajectory and pain management needs: a qualitative interview study protocol.

Introduction: Pain is reported as one of the most troubling symptoms for people with Parkinson's (PwP); however, the literature exploring their lived experience of pain and how to manage it is limited. Pain affects PwP at all stages of their condition and can fluctuate and change over time. Therefore, it is pertinent to speak to PwP to understand their experiences of pain to inform the development of tailored behavioural interventions to manage pain.

Developing nurse and midwife centred rostering principles using co-design: a mixed-methods study.

Background: Current nursing and midwifery rosters are based on guidelines which may no longer adequately meet the needs of health services or staff and often result in decreased job satisfaction, poor health and wellbeing, and high turnover. Little is known about the rostering needs and preferences of contemporary nurses and midwives in Australia. The aim of this study was to identify the rostering concerns, needs and preferences of nurses and midwives, and co-design acceptable, equitable and feasible rostering principles.

SERIAL HEALTH ASSESSMENT WITH STANDARDIZED EXTERNAL SCORING AND HEMOLYMPH EVALUATION IN THE AMERICAN HORSESHOE CRAB ().

Serial health assessment of a managed population of American horseshoe crabs (HSC; ) was performed. Twenty HSC were examined once a month for 7 mon; this included a physical exam with a standardized scoring sheet, HR, morphometrics, and hemolymph evaluation with hemocyte count, copper concentration, and biochemistry panel. The HSC in this population had varying levels of external lesions at enrollment.

Encountering Prescribed Fire: Characterizing the Intersection of Prescribed Fire and Wildfire in the CONUS.

Prescribed fire is applied across the United States as a fuel treatment to manage the impact of wildfires and restore ecosystems. While the recent application of prescribed fire has largely been confined to the southeastern US, the increase in catastrophic wildfires has accelerated the growth of prescribed fire more broadly. To effectively achieve wildfire risk reduction benefits, which includes reducing the amount of smoke emitted, the area treated by prescribed fire must come into contact with a subsequent wildfire.