Mitigating the Risk of QTc Prolongation When Using Haloperidol for Acute Treatment of Cannabinoid Hyperemesis Syndrome in Adolescents and Young Adults.

: Cannabinoid Hyperemesis Syndrome (CHS), associated with long-term cannabinoid use, has been increasingly observed in emergency room visits as more states in the U.S. have legislatively permitted medical and recreational marijuana use.

Addressing Financial Toxicity From a Global Perspective: How to Advance Shared-Learning to Facilitate Change?

Financial Toxicity is a global issue requiring international efforts, but importantly, where to next?

Budesonide, Added to PTCy-Based Regimen, for Prevention of Acute GI GVHD After Allogeneic Stem Cell Transplantation.

Oral budesonide exerts local effects with negligible systemic glucocorticoid activity, due to rapid first-pass metabolism, therefore, could potentially be efficacious in preventing gastrointestinal (GI) acute GVHD (aGVHD). We explored the use of budesonide, added to posttransplant cyclophosphamide (PTCy), tacrolimus, and mycophenolate mofetil, for prevention of GI aGVHD after allogeneic hematopoietic stem cell transplantation (AHSCT) in a prospective observational study and treated 80 patients with a median age of 53 years (range 19-74). Results were compared with a publicly available CIBMTR dataset of 646 patients who received PTCy-based GVHD prophylaxis (CIBMTR Study # GV17-02) (control).

Integrating microfluidic and bioprinting technologies: advanced strategies for tissue vascularization.

Tissue engineering offers immense potential for addressing the unmet needs in repairing tissue damage and organ failure. Vascularization, the development of intricate blood vessel networks, is crucial for the survival and functions of engineered tissues. Nevertheless, the persistent challenge of ensuring an ample nutrient supply within implanted tissues remains, primarily due to the inadequate formation of blood vessels.

Identifying and treating metabolic dysfunction-associated steatotic liver disease among at-risk Veterans.

Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD), an increasing public health concern, remains challenging to diagnose and risk-stratify. We assessed the 1) prevalence of MASLD risk factors among Veterans in Veterans Health Administration (VA) care, 2) factors associated with MASLD diagnosis; and 3) associations between MASLD diagnosis and receipt of care.

Methods: Veterans with MASLD risk factors, including obesity, pre-diabetes, diabetes, or dyslipidemia, were identified using International Classification of Diseases-10 codes and followed in 2019-2022.

PPA1, TRIM68 and FBXO46: Potential Therapeutic Targets for Triple Negative Breast Cancer.

Background: Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer with a high recurrence rate. A new therapeutic intervention is urgently needed to combat this lethal subtype. The identification of biomarkers is also crucial for improving outcomes in TNBC.

Evidence for microbially-mediated tradeoffs between growth and defense throughout coral evolution.

Background: Evolutionary tradeoffs between life-history strategies are important in animal evolution. Because microbes can influence multiple aspects of host physiology, including growth rate and susceptibility to disease or stress, changes in animal-microbial symbioses have the potential to mediate life-history tradeoffs. Scleractinian corals provide a biodiverse, data-rich, and ecologically-relevant host system to explore this idea.

ATM and IRAK1 orchestrate two distinct mechanisms of NF-κB activation in response to DNA damage.

DNA damage in cells induces the expression of inflammatory genes. However, the mechanism by which cells initiate an innate immune response in the presence of DNA lesions blocking transcription remains unknown. Here we find that genotoxic stresses lead to an acute activation of the transcription factor NF-κB through two distinct pathways, each triggered by different types of DNA lesions and coordinated by either ataxia-telangiectasia mutated (ATM) or IRAK1 kinases.

Hyperglycemia causes differential change in macrophage population in the lacrimal gland, conjunctiva and cornea.

Background: Due to its location, the ocular surface is exposed to environmental microbes. Innate immune cells including macrophages are first line defense against infections. exposure to high glucose as well as diabetes-associated hyperglycemia has been shown to affect innate immune cell function and population.

Evaluation of methotrexate Pharmacogenomic variation to predict acute neurotoxicity in children with acute lymphoblastic leukemia.

Background: Methotrexate is an important component of curative therapy in childhood acute lymphoblastic leukemia (ALL), but the role of genetic variation influencing methotrexate clearance and transport in toxicity susceptibility in children with ALL is not well established. Therefore, we evaluated the association between suspected methotrexate pharmacogenomic variants and methotrexate-related neurotoxicity.

Methods: This study included children (aged 2-20 years) diagnosed with ALL (2005-2019) at six treatment centers in the southwest United States.

The molecular basis of pH sensing by the human fungal pathogen TOK potassium channel.

Two-pore domain, outwardly rectifying potassium (TOK) channels are exclusively expressed in fungi. Human fungal pathogen TOK channels are potential antifungal targets, but TOK channel modulation in general is poorly understood. Here, we discovered that TOK (CaTOK) is regulated by extracellular pH, in contrast to TOK channels from other fungal species tested.

Insights into the Activation and Self-Association of Arrestin-1.

Arrestins halt signal transduction by binding to the phosphorylated C-termini of activated G protein-coupled receptors. Arrestin-1, the first subtype discovered, binds to rhodopsin in rod cells. Mutations in , the gene encoding Arrestin-1, are linked to Oguchi disease, characterized by delayed dark adaptation.

BDNF augmentation reverses cranial radiation therapy-induced cognitive decline and neurodegenerative consequences.

Cranial radiation therapy (RT) for brain cancers is often associated with the development of radiation-induced cognitive dysfunction (RICD). RICD significantly impacts the quality of life for cancer survivors, highlighting an unmet medical need. Previous human studies revealed a marked reduction in plasma brain-derived neurotrophic factor (BDNF) post-chronic chemotherapy, linking this decline to a substantial cognitive dysfunction among cancer survivors.

AlphaFold2-Based Characterization of Apo and Holo Protein Structures and Conformational Ensembles Using Randomized Alanine Sequence Scanning Adaptation: Capturing Shared Signature Dynamics and Ligand-Induced Conformational Changes.

Proteins often exist in multiple conformational states, influenced by the binding of ligands or substrates. The study of these states, particularly the apo (unbound) and holo (ligand-bound) forms, is crucial for understanding protein function, dynamics, and interactions. In the current study, we use AlphaFold2, which combines randomized alanine sequence masking with shallow multiple sequence alignment subsampling to expand the conformational diversity of the predicted structural ensembles and capture conformational changes between apo and holo protein forms.

Access to Evaluation for Liver Transplantation in the Veterans Health Administration.

Background: As the largest US provider of cirrhosis care, the Veterans Health Administration (VA) is the ideal setting to assess patient-, clinician-, and site-level barriers to transplant evaluation.

Aims: To assess barriers to transplant evaluation referral among Veterans with cirrhosis or hepatocellular carcinoma (HCC).

Methods: Logistic regression assessed facility, patient, clinical, and distance factors associated with transplant referral for Veterans with cirrhosis or HCC, over 1 year.

Bile duct ligation-induced cirrhosis does not alter the blood-brain barrier permeability to sucrose in rats.

Contradictory results have been reported about the effects of liver diseases on the blood-brain barrier (BBB) permeability to markers. For instance, both an increase and no change in the BBB permeability to BBB markers sodium fluorescein and Evans blue have been reported in experimental cholestasis induced by bile duct ligation (BDL) in rats. These contradictory effects might be due to inherent limitations of these markers and/or methodological issues.

Impact of COVID-19 Pandemic on Emergency Department Visits for Opioid Use Disorder Across University of California Health Centers.

Introduction: Coronavirus 2019 (COVID-19) has had a devastating impact on mental health and access to addiction treatment in the United States, including in California, which resulted in the highest rates of emergency department visits (ED) for opioid poisoning in 2020. As California slowly returns to pre-pandemic normalcy, it remains uncertain whether the rates of opioid-related events have slowed down over time. We hypothesized that the number of opioid-related ED visits were exacerbated after the period of the COVID-19 pandemic and continue at a high rate in the present.

Nicotinamide Riboside and CD38: Covalent Inhibition and Live-Cell Labeling.

Nicotinamide adenine dinucleotide (NAD) is required for a myriad of metabolic, signaling, and post-translational events in cells. Its levels in tissues and organs are closely associated with health conditions. The homeostasis of NAD is regulated by biosynthetic pathways and consuming enzymes.

Safer and efficient base editing and prime editing via ribonucleoproteins delivered through optimized lipid-nanoparticle formulations.

Delivering ribonucleoproteins (RNPs) for in vivo genome editing is safer than using viruses encoding for Cas9 and its respective guide RNA. However, transient RNP activity does not typically lead to optimal editing outcomes. Here we show that the efficiency of delivering RNPs can be enhanced by cell-penetrating peptides (covalently fused to the protein or as excipients) and that lipid nanoparticles (LNPs) encapsulating RNPs can be optimized for enhanced RNP stability, delivery efficiency and editing potency.