Fine-tuning of gene expression through the Mettl3-Mettl14-Dnmt1 axis controls ESC differentiation.

The marking of DNA, histones, and RNA is central to gene expression regulation in development and disease. Recent evidence links N6-methyladenosine (mA), installed on RNA by the METTL3-METTL14 methyltransferase complex, to histone modifications, but the link between mA and DNA methylation remains scarcely explored. This study shows that METTL3-METTL14 recruits the DNA methyltransferase DNMT1 to chromatin for gene-body methylation.

A study of internal structure validity for the American board of surgery in training examination.

Background: As principles of competency-based medical education are implemented into graduate medical education [GME] programs, it is imperative that the assessments employed are reliable and valid. Internal structure is a core component of validity evidence that has been under studied. In this study, we examined elements of the internal structure for the American Board of Surgery In-Training Examination [ABSITE].

ReBreed21-ET: Evaluation of a rapid resynchronization program that allows timed embryo transfer every 21 days.

This study evaluated the efficiency of a rapid resynchronization of ovulation program to allow timed embryo transfer (TET) every 21d in heifer embryo recipients. Holstein heifers (n = 510) had synchronized ovulation using a modified 5d CoSynch program for a TET (D7) after induced ovulation (D0). After TET, heifers were blocked by number of previous TETs and randomized into one of two resynchronization of ovulation programs: Resynch28 (n = 279), a traditional resynch program for TET 35d after previous TET; or ReBreed21-ET, a program designed to allow TET 21d after previous TET.

Microphytobenthos spatio-temporal dynamics across an intertidal gradient in a tropical estuary using Sentinel-2 imagery.

Intertidal mudflats are among the most productive coastal ecosystems, largely because of the activity of the photosynthetic microbial community on the sediment surface, known as microphytobenthos (MPB). While the dynamics of MPB have been extensively studied in temperate estuaries, there is limited research in tropical estuaries. To address this knowledge gap, we investigated the spatio-temporal dynamics of MPB in the Nicoya Gulf (Costa Rica), one of the world's most productive tropical estuaries, using Sentinel-2 images at 10 m spatial resolution from 2018 to 2022.

Housing hardship and health: Longitudinal evidence of the mediating role of health behaviors.

Housing instability is widely recognized as a major environmental factor that significantly shapes both health and overall well-being. This study added to the existing literature by examining the longitudinal relationship between housing-related hardship and self-rated health. Moreover, this study explored health behaviors-specifically substance use and lifestyle behaviors-as potential mediators that link housing hardship to health.

Light buckets and laser beams: mechanisms and applications of photobiomodulation (PBM) therapy.

Photobiomodulation (PBM) therapy, a non-thermal light therapy using nonionizing light sources, has shown therapeutic potential across diverse biological processes, including aging and age-associated diseases. In 2023, scientists from the National Institute on Aging (NIA) Intramural and Extramural programs convened a workshop on the topic of PBM to discuss various proposed mechanisms of PBM action, including the stimulation of mitochondrial cytochrome C oxidase, modulation of cell membrane transporters and receptors, and the activation of transforming growth factor-β1. They also reviewed potential therapeutic applications of PBM across a range of conditions, including cardiovascular disease, retinal disease, Parkinson's disease, and cognitive impairment.

Coronal Plane Alignment of the Medial Column in Isolated Hallux Valgus, Isolated Flatfoot, and Combined Hallux Valgus-Flatfoot.

Background: To provide improved treatment for hallux valgus (HV), we sought to understand more about the pathophysiologic connection between flatfoot deformity and HV by comparing coronal plane alignment of the medial column of the foot for patients with isolated HV, isolated flatfoot, and combined HV-flatfoot vs controls.

Methods: This study retrospectively assessed a consecutive series of 33 patients with combined symptomatic and radiographic HV and flatfoot, 33 isolated symptomatic HV, 33 isolated symptomatic flatfoot, and 33 controls. The medial column alignment was assessed in the coronal plane using 3-dimensional weightbearing computed tomography (WBCT); rotation was measured for the navicular, medial cuneiform, and first metatarsal (M1).

Prevalence of and risk factors for osteoporosis and fragility fracture in adults with cerebral palsy: A systematic review.

Aim: To systematically review the prevalence and incidence of osteoporosis, osteopenia, low bone mass, and fragility fracture in adults with cerebral palsy (CP), and identify the risk factors for osteoporosis and fracture.

Method: A systematic literature search was performed in the MEDLINE, PubMed, CINAHL, AMED, Cochrane Reviews, EMBASE, and EBM database reviews from inception until May 2024. Search terms covered a combination of keywords for CP, fracture, osteoporosis, incidence and prevalence, and risk factors.

Descriptive analysis of interpreter service mode costs & usage in Northwestern Wisconsin pre and peri COVID-19.

Background: Interpreter service mode (in person, audio, or video) can impact patient experiences and engagement in the healthcare system, but clinics must balance quality with costs and volume to deliver services. Videoconferencing and telephone services provide lower cost options, effective where on site interpreters are scarce, or patients with limited English proficiency (LEP) and/or interpreters are unable to visit healthcare centers. The COVID 19 pandemic generated these conditions in Northwest Wisconsin (NWWI).

Targeting unique ligand binding domain structural features downregulates DKK1 in Y537S ESR1 mutant breast cancer cells.

Resistance to endocrine therapies remains a major clinical hurdle in breast cancer. Mutations to estrogen receptor alpha (ERα) arise after continued therapeutic pressure. Next generation selective estrogen receptor modulators and degraders/downregulators (SERMs and SERDs) show clinical efficacy, but responses are often non-durable.

Retrospective analysis of trauma patients transported by dispatch monitored type B ambulances to Dhulikhel Hospital, Kavre, Nepal, 2019-2023.

Background: Timely emergency medical services (EMS) are particularly important among trauma patients, as inefficient EMS systems can result in potentially avoidable death before reaching a hospital. The Dhulikhel Hospital Dispatch Center coordinates and monitors a growing network of ambulances, including seven Type B ambulances staffed with a trained prehospital care provider and medical equipment. This study evaluates the prehospital care and outcomes of trauma patients transported by Type B ambulances to Dhulikhel Hospital's Emergency Department, as monitored by the Dispatch Center.

Spatial-Structural Mechanisms of Racialized Disparities in Overdose Mortality: A Spatiotemporal Analysis.

Efforts to understand and respond to the opioid crisis have focused on overdose fatalities. Overdose mortality rates (ratios of overdoses resulting in death) are rarely examined though they are important indicators of harm reduction effectiveness. Factors that vary across urban communities likely determine which community members are receiving the resources needed to reduce fatal overdose risk.

Tucatinib and trastuzumab in HER2-mutated metastatic breast cancer: a phase 2 basket trial.

Human epidermal growth factor receptor 2 (HER2, also known as ERBB2) signaling promotes cell growth and differentiation, and is overexpressed in several tumor types, including breast, gastric and colorectal cancer. HER2-targeted therapies have shown clinical activity against these tumor types, resulting in regulatory approvals. However, the efficacy of HER2 therapies in tumors with HER2 mutations has not been widely investigated.

Somatic CAG repeat expansion in blood associates with biomarkers of neurodegeneration in Huntington's disease decades before clinical motor diagnosis.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease with the age at which characteristic symptoms manifest strongly influenced by inherited HTT CAG length. Somatic CAG expansion occurs throughout life and understanding the impact of somatic expansion on neurodegeneration is key to developing therapeutic targets. In 57 HD gene expanded (HDGE) individuals, ~23 years before their predicted clinical motor diagnosis, no significant decline in clinical, cognitive or neuropsychiatric function was observed over 4.

Adherence to multi-target stool DNA testing for colorectal cancer screening in the United States.

Purpose: Colorectal cancer (CRC) is the second leading cause of cancer mortality in the USA and is highly preventable, with early screening vital for improving outcomes. This study aimed to evaluate adherence rates of multi-target stool DNA (mt-sDNA) testing, following updated guidelines recommending screening starting at age 45.

Methods: This retrospective cohort study used aggregated data from Exact Sciences Laboratories LLC, examining new users (first-time testers) aged 45-85 with commercial, Medicare, or Medicaid insurance who received mt-sDNA test kits (point-of-care) between January 1, 2023, and June 1, 2023.

Association between herpes simplex virus infection and Alzheimer's disease biomarkers: analysis within the MAPT trial.

In vitro and animal studies have suggested that inoculation with herpes simplex virus 1 (HSV-1) can lead to amyloid deposits, hyperphosphorylation of tau, and/or neuronal loss. Here, we studied the association between HSV-1 and Alzheimer's disease biomarkers in humans. Our sample included 182 participants at risk of cognitive decline from the Multidomain Alzheimer Preventive Trial who had HSV-1 plasma serology and an amyloid PET scan.

Management of Vascular Complications from Button Battery Ingestions.

Purpose: To propose a gastrointestinal bleeding management algorithm that incorporates an endoscopic and imaging scoring system and specifies management of vascular complication from button battery ingestion.

Recent Findings: Button batteries (BB) are found in many electronic devices and ingestions are associated with serious complications especially in cases of unwitnessed ingestions, prolonged impaction, and in children less than 5 years of age. Gastrointestinal bleeding from BB related vascular injury is rare but often rapidly fatal, with a mortality rate as high as 81%.

Neurobehavioral plasticity in the rodent gustatory system induced by regular consumption of a low-calorie sweetener during adolescence.

Habitual consumption of low-calorie sweeteners (LCS) during juvenile-adolescence can lead to greater sugar intake later in life. Here, we investigated if exposure to the LCS Acesulfame Potassium (Ace-K) during this critical period of development reprograms the taste system in a way that would alter hedonic responding for common dietary compounds. Results revealed that early-life LCS intake not only enhanced the avidity for a caloric sugar (fructose) when rats were in a state of caloric need, it increased acceptance of a bitterant (quinine) in Ace-K-exposed rats tested when middle-aged.

A Phase II Trial of Onapristone and Fulvestrant for Patients With ER+ and HER2- Metastatic Breast Cancer.

Background: The SMILE study is a multi-institutional phase II clinical trial to determine the efficacy and safety of an antiprogestin, onapristone, in combination with fulvestrant as second-line therapy for patients with ER+, PgR+/-, HER2- metastatic breast cancer. This study was terminated early and herein, we report patient characteristics, and outcomes.

Methods: Eligibility criteria included disease progression on ≥2 lines of prior therapy, ECOG performance status ≤ 2, measurable disease per RECIST 1.

Consensus and Guidelines on Diagnosis and Management of Polypoidal Choroidal Vasculopathy (PCV) from the Asia-Pacific Vitreo-retina Society (APVRS).

A panel of 21 international experts are formed by the Asia-Pacific Vitreo-retina Society to work out the consensus and guidelines on polypoidal choroidal vasculopathy (PCV). PCV is a common subtype of neovascular age-related macular degeneration and is more prevalent in Asian populations. Recent advancement in imaging technology allows greater understanding of the disease process of PCV.

A lot of noise about nothing? Speech-to-noise ratios rather than noise predict language outcomes in preschoolers.

It has been proposed that a childhood in a noisy household might lead to poor language skills and slow development of language areas of the brain. Notably, a direct link between noisy households and language development has not been confirmed. Households might have high levels of noise for a range of reasons, including situational (near a large road intersection or airport), family (large families), and cultural (differences in beliefs surrounding noise in the home, including media use).

Vitamin D-related genetic variants and prostate cancer risk in Black men.

Background: The relationship between vitamin D and prostate cancer has primarily been characterized among White men. Black men, however, have higher prostate cancer incidence and mortality rates, chronically low circulating vitamin D levels, and ancestry-specific genetic variants in vitamin D-related genes. Here, we examine critical genes in the vitamin D pathway and prostate cancer risk in Black men.