Revealing an unexpectedly low electron injection threshold via reinforced shock acceleration.

Collisionless shock waves, found in supernova remnants, interstellar, stellar, and planetary environments, and laboratories, are one of nature's most powerful particle accelerators. This study combines in situ satellite measurements with recent theoretical developments to establish a reinforced shock acceleration model for relativistic electrons. Our model incorporates transient structures, wave-particle interactions, and variable stellar wind conditions, operating collectively in a multiscale set of processes.

Absence of MCJ/DnaJC15 promotes brown adipose tissue thermogenesis.

Obesity poses a global health challenge, demanding a deeper understanding of adipose tissue (AT) and its mitochondria. This study describes the role of the mitochondrial protein Methylation-controlled J protein (MCJ/DnaJC15) in orchestrating brown adipose tissue (BAT) thermogenesis. Here we show how MCJ expression decreases during obesity, as evident in human and mouse adipose tissue samples.

Genome-wide association study unravels mechanisms of brain glymphatic activity.

Brain glymphatic activity, as indicated by diffusion-tensor imaging analysis along the perivascular space (ALPS) index, is involved in developmental neuropsychiatric and neurodegenerative diseases, but its genetic architecture is poorly understood. Here, we identified 17 unique genome-wide significant loci and 161 candidate genes linked to the ALPS-indexes in a discovery sample of 31,021 individuals from the UK Biobank. Seven loci were replicated in two independent datasets.

Probabilistic nested model selection in pharmacokinetic analysis of DCE-MRI data in animal model of cerebral tumor.

Best current practice in the analysis of dynamic contrast enhanced (DCE)-MRI is to employ a voxel-by-voxel model selection from a hierarchy of nested models. This nested model selection (NMS) assumes that the observed time-trace of contrast-agent (CA) concentration within a voxel, corresponds to a singular physiologically nested model. However, admixtures of different models may exist within a voxel's CA time-trace.

Mutations to transcription factor MAX allosterically increase DNA selectivity by altering folding and binding pathways.

Understanding how proteins discriminate between preferred and non-preferred ligands ('selectivity') is essential for predicting biological function and a central goal of protein engineering efforts, yet the biophysical mechanisms underpinning selectivity remain poorly understood. Towards this end, we study how variants of the promiscuous transcription factor (TF) MAX (H. sapiens) alter DNA specificity and selectivity, yielding >1700 Ks and >500 rate constants in complex with multiple DNA sequences.

Differential bone and vessel type formation at superior and dura periosteum during cranial bone defect repair.

The cranial mesenchyme, originating from both neural crest and mesoderm, imparts remarkable regional specificity and complexity to postnatal calvarial tissue. While the distinct embryonic origins of the superior and dura periosteum of the cranial parietal bone have been described, the extent of their respective contributions to bone and vessel formation during adult bone defect repair remains superficially explored. Utilizing transgenic mouse models in conjunction with high-resolution multiphoton laser scanning microscopy (MPLSM), we have separately evaluated bone and vessel formation in the superior and dura periosteum before and after injury, as well as following intermittent treatment of recombinant peptide of human parathyroid hormone (rhPTH), Teriparatide.

Pre-T cell receptor-α immunodeficiency detected exclusively using whole genome sequencing.

Maturation of αβ lineage T cells in the thymus relies on the formation and cell surface expression of a pre-T cell receptor (TCR) complex, composed of TCRβ chain and pre-TCRα (pTCRα) chain heterodimers, giving rise to a diverse T cell repertoire. Genetic aberrations in key molecules involved in T cell development lead to profound T cell immunodeficiency. Definitive genetic diagnosis guides treatment choices and counseling.

Neutrophil adhesion to vessel walls impairs pulmonary circulation in COVID-19 pathology.

Microthrombus formation is associated with COVID-19 severity; however, the detailed mechanism remains unclear. In this study, we investigated mouse models with severe pneumonia caused by SARS-CoV-2 infection by using our in vivo two-photon imaging system. In the lungs of SARS-CoV-2-infected mice, increased expression of adhesion molecules in intravascular neutrophils prolonged adhesion time to the vessel wall, resulting in platelet aggregation and impaired lung perfusion.

Robust collection and processing for label-free single voxel proteomics.

With advanced mass spectrometry (MS)-based proteomics, genome-scale proteome coverage can be achieved from bulk tissues. However, such bulk measurement lacks spatial resolution and obscures tissue heterogeneity, precluding proteome mapping of tissue microenvironment. Here we report an integrated wet collection of single microscale tissue voxels and Surfactant-assisted One-Pot voxel processing method termed wcSOP for robust label-free single voxel proteomics.

Glucagon-Like Peptide 1 Receptor Agonists and Chronic Lower Respiratory Disease Among Type 2 Diabetes Patients: Replication and Reliability Assessment Across a Research Network.

Introduction: The aim of this study is to use observational methods to evaluate reliability of evidence generated by a study of the effect of glucagon-like peptide 1 receptor agonists (GLP-1RA) on chronic lower respiratory disease (CLRD) outcomes among Type-2 diabetes mellitus (T2DM) patients.

Research Design And Methods: We independently reproduced a study comparing effects of GLP-1RA versus dipeptidyl peptidase-4 inhibitors (DPP4-i) on CLRD outcomes among patients with T2DM and prior CLRD. We reproduced inputs and outputs using the original study data (national administrative claims) and evaluated the robustness of results in comparison to alternate design/analysis decisions.

Evaluation of Drug-Drug Interactions in Pharmacoepidemiologic Research.

Drug-drug interactions (DDIs) represent a significant concern for clinical care and public health, but the health consequences of many DDIs remain largely underexplored. This knowledge gap underscores the critical need for pharmacoepidemiologic research to evaluate real-world health outcomes of DDIs. In this review, we summarize the definitions commonly used in pharmacoepidemiologic DDI studies, discuss common sources of bias, and illustrate through examples how these biases can be mitigated.

Accuracy of pathogen diagnostic codes for acute hematogenous musculoskeletal infections in children.

Administrative databases are powerful tools for pediatric research but lack patient-level microbiology results. This study aimed to determine the accuracy of pathogen discharge diagnosis codes for children hospitalized with acute hematogenous musculoskeletal infections (MSKIs). Medical records for 244 children hospitalized with acute hematogenous MSKIs were manually reviewed to determine which bacterial pathogen, if any, was identified for each MSKI based on microbiology results obtained during the hospitalization.

Long-Term Opioid Therapy and Risk of Opioid Overdose by Derived Clinical Indication in North Carolina, 2006-2018.

Purpose: Long-term opioid therapy (LTOT) has been shown to be associated with opioid overdose, but the definition of LTOT varies widely across studies. We use a rigorous LTOT definition to examine risk of opioid overdose by duration of treatment.

Methods: Data were from a large private health insurance provider in North Carolina linked to mortality records from 2006-2018.

Core Concepts: Self-Controlled Designs in Pharmacoepidemiology.

One of the key challenges in pharmacoepidemiological studies is that of uncontrolled confounding, which occurs when confounders are poorly measured, unmeasured or unknown. Self-controlled designs can help address this issue, as their key comparison is not between people, but periods of time within the same person. This controls for all time-stable confounders (genetics) and in the absence of time-varying confounding negates the need for an external control group.

Characterization of SARS-CoV-2 Diagnostic Tests and Liver Function Tests Among Patients With COVID-19 Diagnosed in Outpatient Settings Using Administrative Healthcare Data and Data From Commercial Laboratories.

Purpose: To characterize select laboratory tests ordered versus reported for patients diagnosed with COVID-19 in administrative healthcare and commercial laboratory data.

Methods: Among patients with an outpatient COVID-19 diagnosis claim in HealthVerity data (01/01/2021-12/31/2022), this study described baseline characteristics and descriptively compared SARS-CoV-2 diagnostic tests and liver function tests from administrative healthcare (insurance claims and hospital billing data) and commercial laboratories, overall and by code type (e.g.

Incidence of Acute Kidney Injury in Relapsed and Refractory Multiple Myeloma treated with Teclistamab versus CAR T-cells.

Background And Hypothesis: Teclistamab, a novel bispecific monoclonal antibody targeting CD3 and B-cell maturation antigen (BCMA), and chimeric antigen receptor T-cell (CAR-T) therapy are promising options for treating relapsed/refractory multiple myeloma (MM). However, the rates of acute kidney injury (AKI) associated with teclistamab remain inadequately characterized. This study aims to compare the incidence, severity, and outcomes of AKI between patients receiving teclistamab and CAR-T therapy.

Slow Down Fluids to Speed Up the Intestine - Exploring Postoperative Ileus in Pediatric Gastrointestinal Surgery.

Introduction: Postoperative ileus is a known complication of gastrointestinal (GI) surgery. In adult populations, ileus is associated with higher amounts of intraoperative intravenous (IV) fluids. This study examines the relationship between intraoperative IV fluids and postoperative ileus in pediatric patients undergoing GI surgery.

Serum Nutrients, Periodontitis and Biological Ageing.

Introduction: Telomeres are nucleotide sequences found at the end of chromosomes, and their shortening is associated with chronological and biological ageing, oxidative stress and malnutrition. Shorter telomeres have been shown to be associated with periodontitis. Dietary nutrients are also influential factors in the aetiology and progression of periodontitis and other chronic inflammatory diseases.

Metal-rich lacustrine sediments from legacy mining perpetuate copper exposure to aquatic-riparian food webs.

Historic copper mining left a legacy of metal-rich tailings resulting in ecological impacts along and within Torch Lake, an area of concern in the Keweenaw Peninsula, Michigan, USA. Given the toxicity of copper to invertebrates, this study assessed the influence of this legacy on present day nearshore aquatic and terrestrial ecosystems. We measured the metal (Co, Cu, Ni, Zn, Cd) and metalloid (As) concentrations in sediment, pore water, surface water, larval and adult insects, and two riparian spider taxa collected from Torch Lake and a nearby reference lake.

Short- and Mid-Term Outcomes Following ALIF and TLIF in L5-S1 Isthmic Spondylolisthesis Patients.

Background: A limited number of studies have compared the outcomes of anterior lumbar interbody fusion (ALIF) to transforaminal lumbar interbody fusion (TLIF) for the treatment of isthmic spondylolisthesis. This study aims to compare postoperative complications between these two surgical approaches.

Methods: A retrospective review was performed using a large national database.

Two rodent suborders have evolved missing amino acids in the lipid-binding region of apolipoprotein E.

The order Rodentia comprises nearly 45% of all extant taxa, currently organized into 31 living families, some 450 genera, and roughly 2010 species (Kelt & Patton, 2020). Considering that rodents began evolving at least 66 million years ago, it is not surprising that they have diversified into five distinct suborders. With the advent of molecular biology, this difference can often be seen at the molecular level as well.