Drug Property Optimization: Design, Synthesis, and Characterization of Novel Pharmaceutical Salts and Cocrystal-Salt of Lumefantrine.

Lumefantrine (LMF) is a low-solubility antimalarial drug that cures acute, uncomplicated malaria. It exerts its pharmacological effects against erythrocytic stages of spp. and prevents malaria pathogens from producing nucleic acid and protein, thereby eliminating the parasites.

Classifying synoptic patterns driving tornadic storms and associated spatial trends in the United States.

Severe convective storms and tornadoes rank among nature's most hazardous phenomena, inflicting significant property damage and casualties. Near-surface weather conditions are closely governed by large-scale synoptic patterns. It is crucial to delve into the involved multiscale associations to understand tornado potential in response to climate change.

Individual and Familial Risk and Promotive Factors for Substance Use Among Multiracial American Young Adults.

Background: Multiracial American adults have the highest rates of binge drinking and illicit drug use of all racial groups, yet little is known about the risk and promotive factors that contribute to their substance use.

Objectives: This study examines how individual factors (i.e.

Phenotypic antibiotic resistance prediction using antibiotic resistance genes and machine learning models in Mannheimia haemolytica.

Mannheimia haemolytica is one of the most common causative agents of bovine respiratory disease (BRD); however, antibiotic resistance in this species is increasing, making treatment more difficult. Integrative-conjugative elements (ICE), a subset of mobile genetic elements (MGE), encoding up to 100 genes have been reported in Mannheimia haemolytica genomes to confer multidrug resistance, including resistance to antibiotics commonly used in the treatment of BRD. However, the presence of antibiotic resistance genes (ARGs) does not always agree with phenotypic resistance.

Limosilactobacillus reuteri fermented brown rice alleviates anxiety improves cognition and modulates gut microbiota in stressed mice.

Chronic stress disrupts gut microbiota homeostasis, contributing to anxiety and depression. This study explored the effects of Limosilactobacillus reuteri fermented brown rice (FBR) on anxiety using an ICR mouse chronic mild stress (CMS) model. Anxiety was assessed through body weight, corticosterone levels, neurotransmitter profiles, and behavioral tests.

Robust Bayesian graphical regression models for assessing tumor heterogeneity in proteomic networks.

Graphical models are powerful tools to investigate complex dependency structures in high-throughput datasets. However, most existing graphical models make one of two canonical assumptions: (i) a homogeneous graph with a common network for all subjects or (ii) an assumption of normality, especially in the context of Gaussian graphical models. Both assumptions are restrictive and can fail to hold in certain applications such as proteomic networks in cancer.

Genetic parameters and genome-wide association studies including the X chromosome for various reproduction and semen quality traits in Nellore cattle.

Background: The profitability of the beef industry is directly influenced by the fertility rate and reproductive performance of both males and females, which can be improved through selective breeding. When performing genomic analyses, genetic markers located on the X chromosome have been commonly ignored despite the X chromosome being one of the largest chromosomes in the cattle genome. Therefore, the primary objectives of this study were to: (1) estimate variance components and genetic parameters for eighteen male and five female fertility and reproductive traits in Nellore cattle including X chromosome markers in the analyses; and (2) perform genome-wide association studies and functional genomic analyses to better understand the genetic background of male and female fertility and reproductive performance traits in Nellore cattle.

In silico characterization of defense system hotspots in Acinetobacter spp.

The bacteria-phage arm race drives the evolution of diverse bacterial defenses. This study identifies and characterizes the defense hotspots in Acinetobacter baumannii using a reference-free approach. Among 4383 high-quality genomes, we found a total of 17,430 phage defense systems and with 54.

Gut microbes modulate the effects of the flavonoid quercetin on atherosclerosis.

Gut bacterial metabolism of dietary flavonoids results in the production of a variety of phenolic acids, whose contributions to health remain poorly understood. Here, we show that supplementation with the commonly consumed flavonoid quercetin impacted gut microbiome composition and resulted in a significant reduction in atherosclerosis burden in conventionally raised (ConvR) Apolipoprotein E (ApoE) knockout (KO) mice but not in germ-free (GF) ApoE KO mice. Metabolomic analysis revealed that consumption of quercetin significantly increased plasma levels of benzoylglutamic acid, 3,4 dihydroxybenzoic acid (3,4-DHBA) and its sulfate-conjugated form in ConvR mice, but not in GF mice supplemented with the flavonoid.

Click Hydrogels to Assess Stiffness-Induced Activation of Pancreatic Cancer-Associated Fibroblasts and Its Impact on Cancer Cell Spreading.

Pancreatic ductal adenocarcinoma (PDAC) is marked by significant desmoplastic reactions, or the accumulation of excessive extracellular matrices. PDAC stroma has abnormally high stiffness, which alters cancer cell behaviors and creates a barrier for effective drug delivery. Unfortunately, clinical trials using a combination of chemotherapy and matrix-degrading enzyme have led to disappointing results, as the degradation of stromal tissue likely accelerated the dissemination of cancer cells.

Chemically defined and dynamic click hydrogels support hair cell differentiation in human inner ear organoids.

The mechanical properties in the inner ear microenvironment play a key role in its patterning during embryonic development. To recapitulate inner ear development in vitro, three-dimensional tissue engineering strategies including the application of representative tissue models and scaffolds are of increasing interest. Human inner ear organoids are a promising model to recapitulate developmental processes; however, the current protocol requires Matrigel that contains ill-defined extracellular matrix components.

Saccades and Blinks Index Cognitive Demand During Auditory Noncanonical Sentence Comprehension.

Noncanonical sentence structures pose comprehension challenges because they require increased cognitive demand. Prosody may partially alleviate this cognitive load. These findings largely stem from behavioral studies, yet physiological measures may reveal additional insights into how cognition is deployed to parse sentences.

Impact of On-Road U.S. Vehicle Electrification and Lightweighting on Critical Materials Demand.

The electrification of the transport sector is crucial for reducing greenhouse gas emissions and the reliance on fossil fuels. Battery electric vehicles (BEVs) depend on critical materials (CMs) for their batteries and electronic components, yet their widespread adoption may face constraints due to the limited availability of CMs. This study assesses the implications of vehicle electrification and lightweighting (material substitution) on the U.

Chemical characterization of polymer and chloride content in waste plastic materials using pyrolysis - direct analysis in real time - high-resolution mass spectrometry.

The increasing global demand for plastic has raised the need for effective waste plastic management due to its long lifetime and resistance to environmental degradation. There is a need for rapid plastic identification to improve the mechanical waste plastic sorting process. This study presents a novel application of Temperature-Programmed Desorption-Direct Analysis in Real Time-High Resolution Mass Spectrometry (TPD-DART-HRMS) that enables rapid characterization of various plastics.

The Financial Impact of Ehlers-Danlos Syndromes on Patients in the United States in 2022.

Objective: To determine the financial impact of Ehlers-Danlos syndromes (EDS) on patients in the United States by examining the medical expenses incurred by patients.

Patients And Methods: We used a convenience sample approach and disseminated a self-reported survey questionnaire to individuals with EDS via patient advocacy organizations and support groups across the country, social media, and health professionals from April 1, 2023, to December 31, 2023. The survey focused on the out-of-pocket medical expenses incurred by patients.

A Pilot Randomized Controlled Trial to Examine the Impact of a Therapy Dog Intervention on Loneliness in Hospitalized Older Adults.

Background And Objectives: Loneliness is linked to significant health threats and is potentially more dangerous than obesity; it affects as many as 29% of noninstitutionalized older adults. Loneliness is exacerbated for those who require inpatient rehabilitation, are displaced from their social networks, spend little time receiving therapy, and are physically inactive and socially isolated. Emerging evidence suggests that companion animals provide a number of health and well-being benefits and that interacting with a trained therapy dog may reduce loneliness.

Histology and Lung Nodule Fluorescence in Intraoperative Molecular Imaging With Pafolacianine.

Background: Intraoperative molecular imaging (IMI) uses a cancer-targeted fluorescent agent injected into patients to localize tumor nodules. Pafolacianine is a folate receptor (FR)-targeted near-infrared fluorescent probe. Almost 10% of patients have false negative fluorescence findings intraoperatively.

Return of Clinically Actionable Pharmacogenetic Results From Molecular Tumor Board DNA Sequencing Data: Workflow and Estimated Costs.

Pharmacogenetic testing can prevent severe toxicities from several oncology drug therapies; it also has the potential to improve the outcomes from supportive care drugs. Paired tumor and germline sequencing is increasingly common in oncology practice; these include sequencing of pharmacogenes, but the germline pharmacogenetic variants are rarely included in the clinical reports, despite many being clinically actionable. We established an informatics workflow to evaluate the clinical sequencing results for pharmacogenetic variants.

Direct View of Gate-Tunable Miniband Dispersion in Graphene Superlattices Near the Magic Twist Angle.

Superlattices from twisted graphene mono- and bilayer systems give rise to on-demand many-body states such as Mott insulators and unconventional superconductors. These phenomena are ascribed to a combination of flat bands and strong Coulomb interactions. However, a comprehensive understanding is lacking because the low-energy band structure strongly changes when an electric field is applied to vary the electron filling.

Controlling Microparticle Aspect Ratio via Photolithography for Injectable Granular Hydrogel Formation and Cell Delivery.

Granular hydrogels are injectable and inherently porous biomaterials assembled through the packing of microparticles. These particles typically have a symmetric and spherical shape. However, recent studies have shown that asymmetric particles with high aspect ratios, such as fibers and rods, can significantly improve the mechanics, structure, and cell-guidance ability of granular hydrogels.

Acute stress differentially influences risky decision-making processes by sex: A hierarchical bayesian analysis.

How does stress influence our decision-making? Although numerous studies have attempted to answer this question, their results have been inconsistent-presumably due to methodological heterogeneity. Drawing on cumulative prospect theory, we examined how acute stress influenced risky decision-making. To this end, we randomly assigned 147 participants to an acute stress induction or control condition and subsequently assessed participants' risky decision-making.

DigiLoCS: A leap forward in predictive organ-on-chip simulations.

Digital twins, driven by data and mathematical modelling, have emerged as powerful tools for simulating complex biological systems. In this work, we focus on modelling the clearance on a liver-on-chip as a digital twin that closely mimics the clearance functionality of the human liver. Our approach involves the creation of a compartmental physiological model of the liver using ordinary differential equations (ODEs) to estimate pharmacokinetic (PK) parameters related to on-chip liver clearance.

An interprofessional model to improve LGBTQ+ specific cultural competence in dental and pharmacy students.

Background: Disproportionate access to healthcare services among the Lesbian, Gay, Bisexual, Transgender, Queer or Questioning and others (LGBTQ+) population can be partially attributed to the lack of cultural competence among healthcare providers. The aim of this study was to evaluate the impact of an interprofessional model in improving cultural competence and clinical preparedness among dental and pharmacy students for providing LGBTQ+ specific care.

Methodology: This study is a retrospective observational study which used a novel interprofessional model of three different LGBTQ+ focused educational interventions within a group of dental and pharmacy students.

Approaches, Barriers, and Facilitators in Statewide Initiative to Combat Opioid Overdose: A Narrative Review of Ohio's Experiences During the HEALing Communities Study.

Objectives: Opioid-associated fatal and non-fatal overdose rates continue to rise. Prehospital overdose education and naloxone distribution (OEND) programs are attractive harm-reduction strategies, as patients who are not transported by EMS after receiving naloxone have limited access to other interventions. This narrative summary describes our experiences with prehospital implementation of evidence-based OEND practices across Ohio as part of the HEALing Communities Study (HCS).

Lebrikizumab decreases type 2 inflammatory biomarker levels in patients with asthma: data from randomized phase 3 trials (LAVOLTA I and II).

Aim: Lebrikizumab is an interleukin (IL)-13 inhibitor that specifically blocks IL-13 signaling. Here, we report the effects of lebrikizumab on asthma serum biomarkers in 2 phase 3 clinical studies.

Methods: LAVOLTA I and LAVOLTA II are replicate, double-blind, placebo-controlled trials with 52-week placebo-controlled treatment periods that evaluated lebrikizumab 37.