Maternal Western Diet Programmes Bile Acid Dysregulation and Hepatic Fibrosis in Fetal and Juvenile Macaques.

Background And Aims: Maternal obesity increases the risk of the paediatric form of metabolic dysfunction-associated steatotic liver disease (MASLD), affecting up to 30% of youth, but the developmental origins remain poorly understood.

Methods: Using a Japanese macaque model, we investigated the impact of maternal Western-style diet (mWSD) or chow diet followed by postweaning WSD (pwWSD) or chow diet focusing on bile acid (BA) homeostasis and hepatic fibrosis in livers from third-trimester fetuses and 3-year-old juvenile offspring.

Results: Juveniles exposed to mWSD had increased hepatic collagen I/III content and stellate cell activation in portal regions.

Transcriptomic Profiling Reveals 17β-Estradiol Treatment Represses Ubiquitin-Proteasomal Mediators in Skeletal Muscle of Ovariectomized Mice.

Background: With a decline of 17β-estradiol (E2) at menopause, E2 has been implicated in the accompanied loss of skeletal muscle mass and strength. We aimed at characterizing transcriptomic responses of skeletal muscle to E2 in female mice, testing the hypothesis that genes and pathways related to contraction and maintenance of mass are differentially expressed in ovariectomized mice with and without E2 treatment.

Methods: Soleus and tibialis anterior (TA) muscles from C57BL/6 ovariectomized mice treated with placebo (OVX) or E2 (OVX + E2) for 60 days, or from skeletal muscle-specific ERα knockout (skmERαKO) mice and wild-type littermates (skmERαWT), were used for genome-wide expression profiling, quantitative real-time PCR and immunoblotting.

Insights into the flexibility of the domain-linking loop in actinobacterial coproheme decarboxylase through structures and molecular dynamics simulations.

Prokaryotic heme biosynthesis in Gram-positive bacteria follows the coproporphyrin-dependent heme biosynthesis pathway. The last step in this pathway is catalyzed by the enzyme coproheme decarboxylase, which oxidatively transforms two propionate groups into vinyl groups yielding heme b. The catalytic reaction cycle of coproheme decarboxylases exhibits four different states: the apo-form, the substrate (coproheme)-bound form, a transient three-propionate intermediate form (monovinyl, monopropionate deuteroheme; MMD), and the product (heme b)-bound form.

A novel method for expressing and purifying large quantities of functional and stable human voltage-gated proton channel (hH1).

Purifying membrane proteins has been the limiting step for studying their structure and function. The challenges of the process include the low expression levels in heterologous systems and the requirement for their biochemical stabilization in solution. The human voltage-gated proton channel (hH1) is a good example of that: the published protocols to express and purify hH1 produce low protein quantities at high costs, which is an issue for systematically characterizing its structure and function.

Adjusting for Ascertainment Bias in Meta-Analysis of Penetrance for Cancer Risk.

Multi-gene panel testing allows efficient detection of pathogenic variants in cancer susceptibility genes including moderate-risk genes such as ATM and PALB2. A growing number of studies examine the risk of breast cancer (BC) conferred by pathogenic variants of these genes. A meta-analysis combining the reported risk estimates can provide an overall estimate of age-specific risk of developing BC, that is, penetrance for a gene.

CaML: Chemistry-informed machine learning explains mutual changes between protein conformations and calcium ions in calcium-binding proteins using structural and topological features.

Proteins' flexibility is a feature in communicating changes in cell signaling instigated by binding with secondary messengers, such as calcium ions, associated with the coordination of muscle contraction, neurotransmitter release, and gene expression. When binding with the disordered parts of a protein, calcium ions must balance their charge states with the shape of calcium-binding proteins and their versatile pool of partners depending on the circumstances they transmit. Accurately determining the ionic charges of those ions is essential for understanding their role in such processes.

Engineered protein G variants for multifunctional antibody-based assemblies.

We have developed a portfolio of antibody-based modules that can be prefabricated as standalone units and snapped together in plug-and-play fashion to create uniquely powerful multifunctional assemblies. The basic building blocks are derived from multiple pairs of native and modified Fab scaffolds and protein G (PG) variants engineered by phage display to introduce high pair-wise specificity. The variety of possible Fab-PG pairings provides a highly orthogonal system that can be exploited to perform challenging cell biology operations in a straightforward manner.

Modeling the response to interleukin-21 to inform natural killer cell immunotherapy.

Natural killer (NK) cells are emerging agents for cancer therapy. Several different cytokines are used to generate NK cells for adoptive immunotherapy including interleukin (IL)-2, IL-12, IL-15 and IL-18 in solution, and membrane-bound IL-21. These cytokines drive NK cell activation through the integration of signal transducers and activators of transcription (STAT) and nuclear factor-kappa B (NF-κB) pathways, which overlap and synergize, making it challenging to predict optimal cytokine combinations for both proliferation and cytotoxicity.

Gene-Air Pollution Interaction and Diversity of Genetic Sampling: The Southern California Children's Health Study.

Gene-environment interactions have been observed for childhood asthma, however few have been assessed in ethnically diverse populations. Thus, we examined how polygenic risk score (PRS) modifies the association between ambient air pollution exposure (nitrogen dioxide [NO], ozone, particulate matter < 2.5 and < 10 μm) and childhood asthma incidence in a diverse cohort.

FDA-approved drugs featuring macrocycles or medium-sized rings.

Macrocycles or medium-sized rings offer diverse functionality and stereochemical complexity in a well-organized ring structure, allowing them to fulfill various biochemical functions, resulting in high affinity and selectivity for protein targets, while preserving sufficient bioavailability to reach intracellular compartments. These features have made macrocycles attractive candidates in organic synthesis and drug discovery. Since the 20th century, more than three-score macrocyclic drugs, including radiopharmaceuticals, have been approved by the US Food and Drug Administration (FDA) for treating bacterial and viral infections, cancer, obesity, immunosuppression, inflammatory, and neurological disorders, managing cardiovascular diseases, diabetes, and more.

Longitudinal measures of peripheral optical quality in young children.

Purpose: To assess longitudinal changes in optical quality across the periphery (horizontal meridian, 60°) in young children who are at high (HR) or low risk (LR) of developing myopia, as well as a small subgroup of children who developed myopia over a 3-year time frame.

Methods: Aberrations were measured every 6 months in 92 children with functional emmetropia at baseline. Children were classified into HR or LR based on baseline refractive error and parental myopia.

RADAR-AD: assessment of multiple remote monitoring technologies for early detection of Alzheimer's disease.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting millions worldwide, leading to cognitive and functional decline. Early detection and intervention are crucial for enhancing the quality of life of patients and their families. Remote Monitoring Technologies (RMTs) offer a promising solution for early detection by tracking changes in behavioral and cognitive functions, such as memory, language, and problem-solving skills.

Cryo-EM SPR structures of Salmonella typhimurium ArnC; the key enzyme in lipid-A modification conferring polymyxin resistance.

Polymyxins are last-resort antimicrobial peptides administered clinically against multi-drug resistant bacteria, specifically in the case of Gram-negative species. However, an increasing number of these pathogens employ a defense strategy that involves a relay of enzymes encoded by the pmrE (ugd) loci and the arnBCDTEF operon. The pathway modifies the lipid-A component of the outer membrane (OM) lipopolysaccharide (LPS) by adding a 4-amino-4-deoxy-l-arabinose (L-Ara4N) headgroup, which renders polymyxins ineffective.

Cardio-renal effect of dapagliflozin and dapagliflozin- saxagliptin combination on CD34 + ve hematopoietic stem cells (HSCs) and podocyte specific markers in type 2 diabetes (T2DM) subjects: a randomized trial.

Introduction: Effects of Dapagliflozin (Dapa) and Dapagliflozin-Saxagliptin combination (Combo) was examined on peripheral blood derived CD34 + Hematopoetic Stem Cells (HSCs) as a cellular CVD biomarker. Both Dapa (a sodium-glucose co-transporter 2 or SGLT2, receptor inhibitor) and Saxagliptin (a Di-peptydl-peptidase-4 or DPP4 enzyme inhibitor) are commonly used type 2 diabetes mellitus or T2DM medications, however the benefit of using the combination has not been evaluated for cardio-renal risk assessment, in a real-life practice setting, compared to a placebo.

Hypothesis: We hypothesized that Dapa will improve the outcomes when compared to placebo and the Combo maybe even more beneficial.

Ultrasound-Based Local Lung Motion Assessment Using Synthetic Lateral Phase.

Background: Ultrasound lung surface motion measurement is valuable for the evaluation of a variety of diseases. Speckle tracking or Doppler-based techniques are limited by the loss of visualization as a tracked point moves under ribs or is dependent.

Methods: We developed a synthetic lateral phase-based algorithm for tracking lung motion to overcome these limitations.

The association of travel distance and other patient characteristics with breast cancer stage at diagnosis and treatment completion at a rural Rwandan cancer facility.

Background: Butaro Cancer Center of Excellence (BCCOE) was founded to serve Rwanda's rural low-income population, providing subsidized cancer diagnosis and treatment with transport stipends for the lowest-income patients. We examined whether travel distance to BCCOE was associated with advanced-stage diagnoses and treatment completion.

Methods: We conducted a retrospective cohort study using medical record data from BCCOE patients with pathologically-confirmed breast cancer from 2012-2016.

Trends and disparities in atrial fibrillation-related mortality among adults with co-morbid diabetes mellitus in the United States.

From 1999 to 2020, age-adjusted mortality rates (AAMR) for atrial fibrillation-related deaths among U.S. adults (age ≥25) with comorbid diabetes mellitus increased significantly with an annual percent change of 6.

A mixed-methods observational study of strategies for success in implementation science: overcoming emergency departments hurdles.

Background: Heart failure is a major public health concern, affecting 6.7 million Americans. An estimated 16% of emergency department (ED) patients with acute heart failure (AHF) are discharged home.

Extremely early initiation of vasopressors might not decrease short-term mortality for adults with septic shock: a systematic review and meta-analysis.

Background: The optimal timing for initiating vasopressor therapy in patients with septic shock remains unclear. This study aimed to assess the impact of early versus late vasopressor initiation on clinical outcomes.

Methods: A systematic review and meta-analysis were conducted by searching PubMed, Embase, and Cochrane databases.

Substance Use Classes Among YMSM in an HIV Digital Health Intervention Program: Implications for Acceptability, Engagement, and Health Outcomes.

Young men who have sex with men (YMSM) have high rates of substance use, which increases their risk for HIV. Digital Health Interventions (DHI) have the potential to address HIV risk overall and reduce harms in the context of substance use. However, there is limited research on how YMSM with different substance use patterns respond to HIV DHIs and how these programs impact participant outcomes.

Acceptability and Feasibility of Self-Collected Dried Blood Spot Specimens for Viral Load Monitoring among Rural Older People Living with HIV.

Self-collected dried blood spot (DBS) samples may be useful in monitoring viral load (VL) in research studies or clinically given that they eliminate the need for participants to travel to study sites or laboratories. Despite this, little information exists about monitoring VL using DBS self-collected at home, and no information exists on DBS for this use among older rural people living with HIV (PLH), a population that could benefit from self-collection given difficulty accessing care. We report on the feasibility and acceptability of self-collected DBS samples, DBS VL results, concordance between self-reported and DBS VL, and factors associated with DBS detectable VL in a rural Southern U.

Ways to Measure Metals: From ICP-MS to XRF.

Purpose Of Review: This review explores the use of Inductively Coupled Plasma Mass Spectrometry (ICP-MS) and X-ray Fluorescence (XRF) for quantifying metals and metalloids in biological matrices such as hair, nails, blood, bone, and tissue. It provides a comprehensive overview of these methodologies, detailing their technological limitations, application scopes, and practical considerations for selection in both laboratory and field settings. By examining traditional and novel aspects of each method, this review aims to guide researchers and clinical practitioners in choosing the most suitable analytical tool based on their specific needs for sensitivity, precision, speed, and sample preparation.

Improved display and detection of small renal stones using photon-counting detector CT compared to conventional energy-integrating detector CT.

Purpose: To compare same-day photon-counting detector CT (PCD-CT) to conventional energy-integrating detector CT (EID-CT) for detection of small renal stones (≤ 3 mm).

Methods: Patients undergoing clinical dual-energy EID-CT for known or suspected stone disease underwent same-day research PCD-CT. Patients with greater than 10 stones and no visible stones under 3 mm were excluded.