Hydrogel biomaterials that stiffen and soften on demand reveal that skeletal muscle stem cells harbor a mechanical memory.

Muscle stem cells (MuSCs) are specialized cells that reside in adult skeletal muscle poised to repair muscle tissue. The ability of MuSCs to regenerate damaged tissues declines markedly with aging and in diseases such as Duchenne muscular dystrophy, but the underlying causes of MuSC dysfunction remain poorly understood. Both aging and disease result in dramatic increases in the stiffness of the muscle tissue microenvironment from fibrosis.

Lipid control and stroke risk in atrial fibrillation patients treated with direct oral anticoagulants and statins.

Introduction: The risk of ischemic stroke and intracerebral hemorrhage (ICH) with intensive lipid control by statins among patients with atrial fibrillation (AF) who require direct oral anticoagulants (DOAC) is unclear. We aimed to determine the risks of ischemic stroke and ICH in AF patients treated with DOAC and statins.

Patients And Methods: In a population-based retrospective cohort study, we identified AF patients concurrently on DOAC and statins from 2015 to 2021 in Hong Kong.

Internal consistency of multi-tier +EDMFT.

The multi-tier +EDMFT scheme is an ab-initio method for calculating the electronic structure of correlated materials. While the approach is free from ad-hoc parameters, it requires a selection of appropriate energy windows for describing low-energy and strongly correlated physics. In this study, we test the consistency of the multi-tier description by considering different low-energy windows for a series of cubic SrXO (X = V, Cr, Mn) perovskites.

High-sensitivity in situ capture of endogenous RNA-protein interactions in fixed cells and primary tissues.

RNA-binding proteins (RBPs) have pivotal functions in RNA metabolism, but current methods are limited in retrieving RBP-RNA interactions within endogenous biological contexts. Here, we develop INSCRIBE (IN situ Sensitive Capture of RNA-protein Interactions in Biological Environments), circumventing the challenges through in situ RNA labeling by precisely directing a purified APOBEC1-nanobody fusion to the RBP of interest. This method enables highly specific RNA-binding site identification across a diverse range of fixed biological samples such as HEK293T cells and mouse brain tissue and accurately identifies the canonical binding motifs of RBFOX2 (UGCAUG) and TDP-43 (UGUGUG) in native cellular environments.

Temporal and Spatial Clustering of Intracerebral Hemorrhage in Cerebral Amyloid Angiopathy.

Objectives: Cerebral amyloid angiopathy (CAA)-associated lobar intracerebral hemorrhage (ICH) has a high risk of recurrence, but the underlying mechanisms remain uncertain. We, therefore, aimed to characterize patterns of recurrent ICH.

Methods: We investigated early recurrent ICH (≥1 recurrent ICH event within 90 days of the index event) and ICH clusters (≥2 ICH events within 90 days at any time point) in 2 large cohorts of consecutive patients with first-ever ICH and available MRI.

Precision Antiplatelet Therapy after Percutaneous Coronary Intervention (Precision PCI) Registry - Informing optimal antiplatelet strategies.

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y receptor inhibitor (clopidogrel, prasugrel, or ticagrelor) is indicated after percutaneous coronary intervention (PCI) to reduce the risk of atherothrombotic events. Approximately 30% of the US population has a CYP2C19 no-function allele that reduces the effectiveness of clopidogrel, but not prasugrel or ticagrelor, after PCI. We have shown improved outcomes with the integration of CYP2C19 genotyping into clinical care to guide the selection of prasugrel or ticagrelor in CYP2C19 no-function allele carriers.

Zfp697 is an RNA-binding protein that regulates skeletal muscle inflammation and remodeling.

Skeletal muscle atrophy is a morbidity and mortality risk factor that happens with disuse, chronic disease, and aging. The tissue remodeling that happens during recovery from atrophy or injury involves changes in different cell types such as muscle fibers, and satellite and immune cells. Here, we show that the previously uncharacterized gene and protein Zfp697 is a damage-induced regulator of muscle remodeling.

Spatial distribution of active compounds in stratum corneum-partitioning between corneocytes and lipid matrix.

The interaction of active substances with molecular structures in stratum corneum (SC) is crucial for the efficacy and safety of cosmetic formulations and topical drugs. However, the molecular architecture of SC is highly complex and methods to unambiguously localize exogenous molecules within SC are lacking. Consequently, little is known about the distribution of actives within SC, and proposed penetration mechanisms through SC are typically limited to simple diffusion via a tortuous (lipid only) or transverse (across corneocytes and lipid matrix) pathway.

How Would You Treat This Inpatient With Type 2 Diabetes Mellitus? Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

Management of hospitalized patients with type 2 diabetes mellitus (T2DM) presents unique challenges. Two recently released guidelines, one from the American Diabetes Association and the other from the Endocrine Society, provide useful recommendations and evidence review to inform the care of medical inpatients with T2DM. These guidelines mostly agree, although there are slight differences in their recommendations.

Replacement of Native with Malted Triticale (x Wittmack) Flour in Dry Pasta: Technological and Nutritional Implications.

The use of native and malted triticale (MT) flour in dry pasta has been limited despite the potential of triticale in cereal-based food production. In this study, triticale-based dry spaghetti with increasing levels of substitution (0, 25, 50, and 75 g/100 g /) of MT flour were formulated and analyzed. Samples were analyzed for technological and nutritional traits, including the in vitro starch and protein digestions.

FAST-EM array tomography: a workflow for multibeam volume electron microscopy.

Elucidating the 3D nanoscale structure of tissues and cells is essential for understanding the complexity of biological processes. Electron microscopy (EM) offers the resolution needed for reliable interpretation, but the limited throughput of electron microscopes has hindered its ability to effectively image large volumes. We report a workflow for volume EM with FAST-EM, a novel multibeam scanning transmission electron microscope that speeds up acquisition by scanning the sample in parallel with 64 electron beams.

Towards cross-application model-agnostic federated cohort discovery.

Objectives: To demonstrate that 2 popular cohort discovery tools, Leaf and the Shared Health Research Information Network (SHRINE), are readily interoperable. Specifically, we adapted Leaf to interoperate and function as a node in a federated data network that uses SHRINE and dynamically generate queries for heterogeneous data models.

Materials And Methods: SHRINE queries are designed to run on the Informatics for Integrating Biology & the Bedside (i2b2) data model.

Associations of Blood Cadmium Levels With Osteoarthritis Among US Adults in NHANES 2013-2018.

Background: Osteoarthritis (OA) is a global public health problem, and limited information is available on the effects of Cd on OA. The purpose of this study is to explore the relationship between Cd and OA.

Method: Weighted multivariable logistic regression model, trend test, restricted cubic spline, and stratified analysis were used to study the association between BCd and OA.

Acousto-optic-based time domain electric field sensor for magnetic resonance imaging applications.

An acousto-optic (AO)-based electric field sensor is presented for time domain measurement under magnetic resonance imaging (MRI). A fully MR-compatible sensor is designed and fabricated using a phase-shifted fiber Bragg grating mechanically coupled to a piezoelectric transducer. Mechanical resonance of the piezoelectric transducer is matched to the operating frequencies of commonly used MRI systems to increase the sensitivity of the sensor.

The small molecule inhibitor of SARS-CoV-2 3CLpro EDP-235 prevents viral replication and transmission in vivo.

The COVID-19 pandemic has led to the deaths of millions of people and severe global economic impacts. Small molecule therapeutics have played an important role in the fight against SARS-CoV-2, the virus responsible for COVID-19, but their efficacy has been limited in scope and availability, with many people unable to access their benefits, and better options are needed. EDP-235 is specifically designed to inhibit the SARS-CoV-2 3CLpro, with potent nanomolar activity against all SARS-CoV-2 variants to date, as well as clinically relevant human and zoonotic coronaviruses.

Genetic Associations With an Amyotrophic Lateral Sclerosis Reversal Phenotype.

Background And Objectives: The term "ALS Reversal" describes patients who initially meet diagnostic criteria for amyotrophic lateral sclerosis (ALS) or had clinical features most consistent with progressive muscular atrophy (PMA) but subsequently demonstrated substantial and sustained clinical improvement. The objective of this genome-wide association study (GWAS) was to identify correlates of this unusual clinical phenotype.

Methods: Participants were recruited from a previously created database of individuals with the ALS Reversal phenotype.

Neonatal Outcomes after Maternal Biomarker-Guided Preterm Birth Intervention: The AVERT PRETERM Trial.

The AVERT PRETERM trial (NCT03151330) evaluated whether screening clinically low-risk pregnancies with a validated maternal blood biomarker test for spontaneous preterm birth (sPTB) risk, followed by preventive treatments for those screening positive, would improve neonatal outcomes compared to a clinically low-risk historical population that had received the usual care. Prospective arm participants with singleton non-anomalous pregnancies and no PTB history were tested for sPTB risk at 19-20 weeks' gestation and followed up with after neonatal discharge. Screen-positive individuals (≥16% sPTB risk) were offered vaginal progesterone (200 mg) and aspirin (81 mg) daily, with twice-weekly nurse phone calls.

Co-Occurring Methylenetetrahydrofolate Reductase () rs1801133 and rs1801131 Genotypes as Associative Genetic Modifiers of Clinical Severity in Rett Syndrome.

Aim: Remethylation disorders such as 5,10-methylenetetrahydrofolate reductase () deficiency reduce the remethylation of homocysteine to methionine. The resulting hyperhomocysteinemia can lead to serious neurological consequences and multisystem toxicity. The role of genotypes has not been investigated in patients with Rett Syndrome (RTT).