Validating Structural Predictions of Conjugated Macromolecules in Espaloma-Enabled Reproducible Workflows.

We incorporated Espaloma forcefield parameterization into MoSDeF tools for performing molecular dynamics simulations of organic molecules with HOOMD-Blue. We compared equilibrium morphologies predicted for perylene and poly-3-hexylthiophene (P3HT) with the ESP-UA forcefield in the present work against prior work using the OPLS-UA forcefield. We found that, after resolving the chemical ambiguities in molecular topologies, ESP-UA is similar to GAFF.

Alcohol Use Disorder and the Gut-Brain Axis: A Narrative Review of the Role of Gut Microbiota and Implications for Treatment.

Alcohol use disorder (AUD) affects millions of people worldwide and can lead to deleterious physical and social consequences. Recent research has highlighted not only the effect of alcohol on the gut microbiome, but also the role of the gut microbiome and the gut-brain axis in the development and maintenance of alcohol use disorder. This review provides an overview of the reciprocal relationship between alcohol consumption and the gut microbiome, including the effects of alcohol on gut microbial composition, changes in gut microbial metabolites in response to alcohol consumption, and how gut microbial metabolites may modulate alcohol use behavior.

Comprehensive Metabolomics in Mouse Mast Cell Model of Allergic Rhinitis for Profiling, Modulation, Semiquantitative Analysis, and Pathway Analysis.

Allergic rhinitis affects millions globally, causing significant discomfort and reducing the quality of life. This study investigates the metabolic alterations in murine mast cells (MC/9) under allergic rhinitis conditions induced by lipopolysaccharide (LPS) stimulation, employing UHPLC-QTOF-MS-based untargeted and targeted metabolomics. The analysis identified 44 significantly regulated metabolites, including histamine, leukotrienes, prostaglandins, thromboxanes, and ceramides.

Tetrahydrobiopterin in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Friend or Foe?

Myalgic Encephalomyelitis or Chronic Fatigue Syndrome (ME/CFS) is a chronic multisystem disease characterized by severe muscle fatigue, pain, dizziness, and brain fog. The two most common symptoms are post-exertional malaise (PEM) and orthostatic intolerance (OI). ME/CFS patients with OI (ME+OI) suffer from dizziness or faintness due to a sudden drop in blood pressure while maintaining an upright posture.

Caffeic Acid Phenethyl Ester Protects Neurons Against Oxidative Stress and Neurodegeneration During Traumatic Brain Injury.

Traumatic brain injury (TBI) is an inflammatory disease causing neurodegeneration. One of the consequences of inflammation is an elevated blood level of fibrinogen (Fg). Earlier we found that extravasated Fg induced an increased expression of neuronal nuclear factor kappa B (NF-κB) p65.

Ethanol Disrupts the Protective Crosstalk Between Macrophages and HBV-Infected Hepatocytes.

About 296 million people worldwide are living with chronic hepatitis B viral (HBV) infection, and outcomes to end-stage liver diseases are potentiated by alcohol. HBV replicates in hepatocytes, but other liver non-parenchymal cells can sense the virus. In this study, we aimed to investigate the regulatory effects of macrophages on HBV marker and interferon-stimulated genes (ISGs) expressions in hepatocytes.

A Multidisciplinary Approach to Diagnosing Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN): Practical Recommendations and Insights from Countries of the Gulf Cooperation Council.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive orphan hematopoietic malignancy characterized by cutaneous and systemic hematologic involvement. BPDCN is frequently misidentified, but early, accurate diagnosis is critical to extending patient survival using tagraxofusp, a first-in-class CD123-targeted therapy, and increasing their chances of receiving a potentially curative stem cell transplantation. Cases of BPDCN in countries of the Gulf Cooperation Council are lower than the extrapolated incidence from other geographic locations due to lack of awareness of key diagnostic features, lack of consensus on the minimal phenotype for diagnosis, and lack of local immunohistochemistry testing facilities, contributing to underdiagnosis in this region.

Exploring the Role of Communication Asset Mapping (CAM) as a Strategy to Promote Hereditary Cancer Risk Assessment Information Within African American Communities.

: African Americans (AAs) carry the largest burden for almost every type of cancer in the US and are also more likely to die from cancer. Approximately 10% of cancers can be explained by a hereditary factor and detected earlier. Many AAs, however, have inequitable access to hereditary cancer risk assessment (HCRA) tools and information, further exacerbating disparities in cancer rates.

The Impact of Ageing on Diaphragm Function and Maximal Inspiratory Pressure: A Cross-Sectional Ultrasound Study.

: The effects of ageing on the diaphragm are unclear. This study examined the association between ageing and diaphragm thickness, thickening fraction (TF), and diaphragm excursion (DE) as assessed by ultrasonography after adjusting for other factors. The relationship between these parameters and maximal inspiratory pressure (MIP) was also investigated.

The efficacy and safety of rhGH treatment combined with letrozole/GnRHa in adolescent boys.

Objective: In boys during puberty who were undergoing recombinant human growth hormone (rhGH) treatment, we compared the therapeutic efficacy on growth, and any adverse reactions, of co-therapy with either letrozole or gonadotropin-releasing hormone analog (GnRHa).

Methods: Fifty-six pubertal growth hormone deficiency (GHD) boys were studied, they were treated with the combination of letrozole and rhGH (letrozole group, n = 28) or the combination of GnRHa and rhGH (GnRHa group, n = 28) for at least one year. Eighteen patients in the letrozole group and seventeen patients in the GnRHa group attained final adult height (FAH).

Impact of frequent ARID1A mutations on protein stability provides insights into cancer pathogenesis.

The ARID1A gene, frequently mutated in cancer, encodes the AT-rich interactive domain-containing protein 1 A, a key component of the chromatin remodeling SWI/SNF complex. The ARID1A protein features a conserved DNA-binding domain (ARID domain) of approximately 100 residues crucial for its function. Despite the frequency of mutations, the impact on ARID1A's stability and contribution to cancer progression remains unclear.

Unraveling complexity and leveraging opportunities in uncommon breast cancer subtypes.

Special histologic subtypes of breast cancer (BC) exhibit unique phenotypes and molecular profiles with diagnostic and therapeutic implications, often differing in behavior and clinical trajectory from common BC forms. Novel methodologies, such as artificial intelligence may improve classification. Genetic predisposition plays roles in a subset of cases.

The effect of a 14-day Gymnema sylvestre intervention to reduce sugar intake in people self-identifying with a sweet tooth.

Gymnema sylvestre (GS) contains gymnemic acids which can reversibly suppress sweet taste responses. This randomised crossover study aimed to investigate whether supplemental GS use can reduce sugar cravings, sweet food desire and consumption among adults that identify as high sweet food consumers (having a 'sweet tooth'). Participants were told three different mints were trialled to avoid bias.

Designed mosaic nanoparticles enhance cross-reactive immune responses in mice.

Nanoparticle vaccines displaying combinations of SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs) could protect against SARS-CoV-2 variants and spillover of zoonotic sarbecoviruses into humans. Using a computational approach, we designed variants of SARS-CoV-2 RBDs and selected 7 natural sarbecovirus RBDs, each predicted to fold properly and abrogate antibody responses to variable epitopes. RBDs were attached to 60-mer nanoparticles to make immunogens displaying two (mosaic-2s), five (mosaic-5), or seven (mosaic-7) different RBDs for comparisons with mosaic-8b, which elicited cross-reactive antibodies and protected animals from sarbecovirus challenges.

Is Weight Loss the Main Driver for A1C Improvement by Glucagon-Like Peptide 1 (GLP-1) Receptor Agonists? A 2.5-Year Analysis in Real-World Clinical Practice.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are established treatment options for type 2 diabetes (T2D). In addition to their glycemic benefit, GLP-1 RAs also induce weight loss by suppressing appetite via hypothalamic pathways. However, it remains unclear whether weight reduction is the primary driver of glycemic improvement.

Alcohol-induced liver injury is mediated via α4-containing nicotinic acetylcholine receptors expressed in hepatocytes.

Background: Our previous study demonstrated that alcohol induced the expression of the α4 subunit of nicotinic acetylcholine receptors (nAChRs) in the livers of wild type mice (WT), and that whole-body α4 nAChR knockout mice (α4KO) showed protection against alcohol-induced steatosis, inflammation, and injury. Based on these findings, we hypothesized that hepatocyte-specific α4 nAChRs may directly contribute to the detrimental effects of alcohol on the liver.

Methods: Hepatocyte-specific α4 knockout mice (α4HepKO) were generated, and the absence of α4 nAChR was confirmed through PCR of genomic DNA.

Impacts of amino acid-linked platinum(II) complexes on DNA structure.

The discovery of cisplatin (cisPt) as an effective anticancer agent was a milestone in the health industry. Despite its success, undesired side effects and acquired resistance still limit the therapeutic usefulness of cisPt. Intrastrand adduct formation at consecutive purines and structural modifications of DNA caused by platinum(II) complexes are important factors for antitumor efficacy.

Biomonitoring PhIP, a Potential Prostatic Carcinogen, in the Hair of Healthy Men of African and European Ancestry.

Heterocyclic aromatic amines (HAAs), formed during the cooking of meat, are potential human carcinogens, underscoring the need for long-lived biomarkers to assess exposure and cancer risk. Frequent consumption of well-done meats containing 2-amino-1-methyl-6-phenylimidazo[4,5-]pyridine (PhIP), a prevalent HAA that is a prostatic carcinogen in rodents and DNA-damaging agent in human prostate cells, has been linked to aggressive prostate cancer (PC) pathology. African American (AA) men face nearly twice the risk for developing and dying from PC compared to White men.

The Role of Partnerships in Supporting COVID-19 Vaccine Uptake Among Migrants: A Qualitative Case Study from Tamil Nadu and Punjab, India.

Background: During the COVID-19 pandemic, migrant populations remained under-immunized due to limited access to health care, language barriers, and vaccine hesitancy. The USAID-funded MOMENTUM Routine Immunization Transformation and Equity project supported the government in collaborating with various local health and non-health partners to identify and vaccinate migrants. This case study examines the roles of project partners and the strategies each entity implemented to increase COVID-19 vaccine uptake among migrants, as well as the perceptions regarding the effectiveness of these strategies.

Fast Hadamard-Encoded 7T Spectroscopic Imaging of Human Brain.

: The increased SNR available at 7T combined with fast readout trajectories enables accelerated spectroscopic imaging acquisitions for clinical applications. In this report, we evaluate the performance of a Hadamard slice encoding strategy with a 2D rosette trajectory for multi-slice fast spectroscopic imaging at 7T. : Moderate-TE (~40 ms) spin echo and J-refocused polarization transfer sequences were acquired with simultaneous Hadamard multi-slice excitations and rosette in-plane encoding.

Modulation of Stemness and Differentiation Regulators by Valproic Acid in Medulloblastoma Neurospheres.

Changes in epigenetic processes such as histone acetylation are proposed as key events influencing cancer cell function and the initiation and progression of pediatric brain tumors. Valproic acid (VPA) is an antiepileptic drug that acts partially by inhibiting histone deacetylases (HDACs) and could be repurposed as an epigenetic anticancer therapy. Here, we show that VPA reduced medulloblastoma (MB) cell viability and led to cell cycle arrest.

Differential Impact of Risk Factors for Cognitive Decline in Heterosexual and Sexual Minority Older Adults in England.

Background/objectives: Sexual minority older adults (SMOAs) report greater subjective cognitive decline (SCD) than heterosexual older adults (HOAs). This study aimed to compare the impact of multiple psycho-social risk factors on objective and subjective cognitive decline in HOAs and SMOAs.

Methods: Two samples of self-identified HOAs and SMOAs were selected from the English Longitudinal Study of Ageing.

Patient "No-Show" Prior to Elective Primary Total Hip Arthroplasty Increases Risk of Postoperative Anemia.

Background: Patients who "no-show" (NS) clinical appointments are at a higher risk of poor healthcare outcomes. The objective of this study was to evaluate and characterize the relationship between patient NS prior to primary total hip arthroplasty (THA) and 90-day complication risk after THA.

Methods: We retrospectively reviewed 4147 patients undergoing primary THA.

Attenuating hyperammonemia preserves protein synthesis and muscle mass via restoration of perturbed metabolic pathways in bile duct-ligated rats.

Sarcopenia and hepatic encephalopathy (HE) are complications of chronic liver disease (CLD), which negatively impact clinical outcomes. Hyperammonemia is considered to be the central component in the pathogenesis of HE, however ammonia's toxic effects have also been shown to impinge on extracerebral organs including the muscle. Our aim was to investigate the effect of attenuating hyperammonemia with ornithine phenylacetate (OP) on muscle mass loss and associated molecular mechanisms in rats with CLD.

Cushing's syndrome related to higher rates and earlier onset of cataract: A nationwide retrospective cohort study.

Purpose: To investigate the risk of cataract in patients with Cushing's syndrome (CS) and evaluate whether disease onset occurs at an earlier age compared to general population.

Methods: A nationwide retrospective matched-cohort study including individuals diagnosed with endogenous CS from 2000 to 2023. Patients with CS were matched in a 1:5 ratio with a control group individually matched for age, sex, socioeconomic status, and body mass index.