Prolonged persistence of mutagenic DNA lesions in somatic cells.

DNA is subject to continual damage, leaving each cell with thousands of individual DNA lesions at any given moment. The efficiency of DNA repair means that most known classes of lesion have a half-life of minutes to hours, but the extent to which DNA damage can persist for longer durations remains unknown. Here, using high-resolution phylogenetic trees from 89 donors, we identified mutations arising from 818 DNA lesions that persisted across multiple cell cycles in normal human stem cells from blood, liver and bronchial epithelium.

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.

Mind the leaf anatomy while taking ground truth with portable chlorophyll meters.

A wide range of portable chlorophyll meters are increasingly being used to measure leaf chlorophyll content as an indicator of plant performance, providing reference data for remote sensing studies. We tested the effect of leaf anatomy on the relationship between optical assessments of chlorophyll (Chl) against biochemically determined Chl content as a reference. Optical Chl assessments included measurements taken by four chlorophyll meters: three transmittance-based (SPAD-502, Dualex-4 Scientific, and MultispeQ 2.

Implementing Mutational Epidemiology on a Global Scale: Lessons from Mutographs.

The Mutographs Cancer Grand Challenge team aimed to discover unknown causes of cancer through mutational epidemiology, an alliance of cancer epidemiology and somatic genomics. By generating whole-genome sequences from thousands of cancers and normal tissues from more than 30 countries on five continents, it discovered unsuspected mutagenic exposures affecting millions of people, raised the possibility that some carcinogens act by altering forces of selection in tissue microenvironments rather than by mutagenesis, and demonstrated changes to the direction of somatic evolution in normal cells of the human body in response to exogenous exposures and noncancer diseases. See related article by Bressan et al.

Estimating optimal thresholds for adherence to RASA medications among older adults with hypertension.

Background: The Centers for Medicare and Medicaid Services (CMS) Star Ratings program incentivizes health plans in Medicare to improve performance on a variety of quality measures such as adherence to renin-angiotensin system antagonists (RASAs). Adherence to RASA medications, defined as having a proportion of days covered (PDC) of at least 80%, has been improving for several years, suggesting that further investigation is needed to assess the appropriateness of the current 80% PDC threshold for medication adherence as an indicator of quality. The 80% PDC threshold has been found to be associated with improved health care resource utilization outcomes; however, little evidence exists to show that this threshold is optimal.

A Five-Year Prospective, Randomized, Open-Label Study of Standard-Dose Versus Low-Dose Prolonged-Release Tacrolimus With or Without Angiotensin-Converting Enzyme Inhibitor or Angiotensin II Receptor Blocker Post Kidney Transplantation.

Introduction: Novel approaches to improve long-term outcomes in kidney transplant recipients are required. Here, we present the 5-year data from a multicenter, prospective, Phase 3b trial evaluating treatment outcomes with standard (STD) or low (LOW) dose prolonged-release tacrolimus (TAC) combined with ACEi/ARB or other antihypertensive therapy (OAHT) in Canadian kidney transplant recipients.

Methods: Adult de novo kidney transplant recipients were randomized 2 × 2 to STD or LOW dose TAC and ACEi/ARB or OAHT.

Community-Engaged Insights: Understanding the Housing Needs of Rural Caregivers During Hospital Treatment.

Purpose: This study explored the experiences of rural caregivers who require temporary housing during hospital treatment when healthcare is not available in their home communities. Understanding these experiences can identify challenges and inform solutions for improving rural access to healthcare.

Methods: We conducted a community-engaged qualitative study using semi-structured interviews with caregivers who stayed at a healthcare hospitality house in Charlotte, NC.

Pulsed Electromagnetic Fields for Cervical Spine Fusion in Patients with Risk Factors for Pseudarthrosis.

Background: Certain demographics and/or risk factors contribute to complications following cervical spinal surgery including pseudarthrosis, prolonged pain, and reduced quality of life (QoL). Pulsed electromagnetic field (PEMF) stimulation is a non-invasive therapy that may enhance fusion success in at-risk patients.

Objective: To evaluate the safety and efficacy of post-operative adjunctive PEMF therapy following cervical spinal surgery in subjects at risk for pseudarthrosis.

The genomic and clinical consequences of replacing procarbazine with dacarbazine in escalated BEACOPP for Hodgkin lymphoma: a retrospective, observational study.

Background: Procarbazine-containing chemotherapy regimens are associated with cytopenias and infertility, suggesting stem-cell toxicity. When treating Hodgkin lymphoma, procarbazine in escalated-dose bleomycin-etoposide-doxorubicin-cyclophosphamide-vincristine-procarbazine-prednisolone (eBEACOPP) is increasingly replaced with dacarbazine (eBEACOPDac) to reduce toxicity. We aimed to investigate the impact of this drug substitution on the mutation burden in stem cells, patient survival, and toxicity.

An analysis of perceptions and thoughts of rapid weight loss in Olympic weightlifters.

Background: Weight-class athletes commonly engage in rapid weight loss (RWL) practices.

Aim: Investigate attributed RWL perceptions and thoughts of UK-based Olympic weightlifters.

Methods: Participants (n: 39, male: 22, female: 17) were selected from International Weightlifting Federation populations, 85% had previously acutely reduced pre-competition body mass.

Protection induced by Streptococcus pneumoniae extracellular vesicles against nasal colonization and invasive infection in mice and the role of PspA.

Diseases caused by Streptococcus pneumoniae (pneumococcus) produce a great impact on public health, killing about one million people annually despite available vaccines. Recent research has revealed that the pneumococcus produces extracellular vesicles (pEVs), which display selective cargo and hold potential for vaccine development. Here, we evaluated the immunogenicity and protective potential of pEVs derived from a non-encapsulated pneumococcal strain (R6) using murine models of pneumococcal colonization and invasive pneumonia.

Patient perceptions of their experience with comprehensive medication reviews: A framework for continued quality improvement.

Background: A comprehensive medication review (CMR) is an annual service offered to eligible Medicare Part D beneficiaries as a component of the Medication Therapy Management program. However, little is known about the most meaningful aspect of CMRs from the patient's perspective. This information is necessary to help improve the service.

Workplace Structures and Culture That Support the Wellbeing of People with an Intellectual Disability.

There is little research on health-promoting workplace settings focused on people with an intellectual disability. There are a range of supported and open employment workplaces where people with an intellectual disability work, and this is an important setting that can influence health and wellbeing outcomes. The health promotion research that has been conducted with people with an intellectual disability has been programmatic in focus and lacks a broader settings and ecological perspective.

Loss of DOT1L function disrupts neuronal transcription, animal behavior, and leads to a novel neurodevelopmental disorder.

Individuals with monoallelic pathogenic variants in the histone lysine methyltransferase DOT1L display global developmental delay and varying congenital anomalies. However, the impact of monoallelic loss of remains unclear. Here, we present a largely female cohort of 11 individuals with variants with developmental delays and dysmorphic facial features.

Examining the role of common variants in rare neurodevelopmental conditions.

Although rare neurodevelopmental conditions have a large Mendelian component, common genetic variants also contribute to risk. However, little is known about how this polygenic risk is distributed among patients with these conditions and their parents nor its interplay with rare variants. It is also unclear whether polygenic background affects risk directly through alleles transmitted from parents to children, or whether indirect genetic effects mediated through the family environment also play a role.

Building robust, proportionate, and timely approaches to regulation and evaluation of digital mental health technologies.

Demand for mental health services exceeds available resources globally, and access to diagnosis and evidence-based treatment is affected by long delays. Digital mental health technologies present an opportunity to reimagine the delivery of mental health support by providing innovative, effective, and tailored approaches that meet people's individual preferences and goals. These technologies also present new challenges, however, and efforts must be made to ensure they are safe and effective.

A scoping review of transmission models for soil-transmitted helminth infections to underpin the development of a transmission model for .

Soil-transmitted helminth (STH) infections afflict people worldwide, especially in tropical and subtropical regions. is distinctive from other STH nematodes by its complex life cycle features of autoinfection, parthenogenesis, and environmental reproduction. This scoping review aims to identify the structures, features, and techniques employed in existing STH models, emphasizing their potential application in describing infection dynamics.

Testosterone suppression and recovery in patients with advanced prostate cancer treated with intermittent androgen deprivation therapy with relugolix.

Background And Objectives: Intermittent androgen deprivation therapy (iADT) may result in measurable improvements in quality of life over continuous ADT in patients with advanced prostate cancer (aPC). Here, we studied time to castration and testosterone recovery in real-world patients with aPC undergoing iADT with relugolix.

Methods And Design: Eligibility criteria for this retrospective study were histologically confirmed through the diagnosis of aPC and initiation of iADT with relugolix.

Pneumococcal extracellular vesicles mediate horizontal gene transfer via the transformation machinery.

Bacterial cells secrete extracellular vesicles (EVs), the function of which is a matter of intense investigation. Here, we show that the EVs secreted by the human pathogen (pneumococcus) are associated with bacterial DNA on their surface and can deliver this DNA to the transformation machinery of competent cells. These findings suggest that EVs contribute to gene transfer in Gram-positive bacteria and, in doing so, may promote the spread of drug resistance genes in the population.

Considerations for regulation and evaluation of digital mental health technologies.

Digital mental health technologies (DMHTs) are becoming well established within mental health services and through direct-to-consumer models. Due to their scalable nature, DMHTs may support services to bridge the gap between demand and the available workforce, particularly where existing pathways have long delays or restricted capacity. Challenges and risks associated with DMHTs also need consideration.

The Organisational Characteristics That Enable Successful Employment Transition for People With Intellectual Disabilities.

Background: Social enterprises have the potential to address some of the current barriers that people with an intellectual disability experience in transitioning to open employment opportunities. However, it is unknown in detail how social enterprises are able to facilitate this transition, which limits ability to scale-up these organisational characteristics and strategies.

Method: Twenty-seven in-depth interviews were conducted with staff, supported employees and partner organisations of a social enterprise to understand the organisational characteristics that enables successful transitions.

Interventions for people with perceptual disorders after stroke: the PIONEER scoping review, Cochrane systematic review and priority setting project.

Background: Stroke often affects recognition and interpretation of information from our senses, resulting in perceptual disorders. Evidence to inform treatment is unclear.

Objective: To determine the breadth and effectiveness of interventions for stroke-related perceptual disorders and identify priority research questions.