An mpox quadrivalent mRNA vaccine elicits sustained and protective immunity in mice against lethal vaccinia virus challenge.

Assessing the long-term efficacy of MPXV vaccine candidates is crucial for the global response to the ongoing mpox epidemic. Built upon our previous study of the mpox quadrivalent mRNA vaccine, herein we reported that MPXV-1103 could elicit sustained humoral and cellular immunity in mice, including the induction of MPXV A35/B6/A29/M1-specific IgG antibodies, VACV neutralizing antibodies and activated cytotoxic CD8T cells, which provides 100% protection against lethal VACV challenge even at 280 days after the first vaccination. Our results provide critical insights for orthopoxvirus vaccine development.

A Systematic Search and Review of Registered Pharmacological Therapies Investigated to Improve Outcomes after a Stroke.

Introduction: Stroke burden is largely due to long-term impairments requiring prolonged care and loss of productivity. We aim to identify and assess studies of different registered pharmacological therapies as treatments for improving post-stroke impairments and/or disabilities.

Methods: In a systematic search and review (PROSPERO registration: CRD42022376973), studies of treatments that have been investigated as recovery-enhancing or recovery-promoting treatments in adult patients who had suffered a stroke will be searched for, screened, and reviewed based on the following: participants (P): adult humans, aged 18 years or older, diagnosed with stroke; interventions (I): registered or marketed pharmacological therapies that have been investigated as recovery-enhancing or recovery-promoting treatments in stroke; comparators (C): active or placebo or no comparator; outcomes (O): stroke-related neurological impairments and functional/disability assessments.

Combined Quantitative amyloid-β PET and Structural MRI Features Improve Alzheimer's Disease Classification in Random Forest Model - A Multicenter Study.

Rationale And Objectives: Prior to clinical presentations of Alzheimer's Disease (AD), neuropathological changes, such as amyloid-β and brain atrophy, have accumulated at the earlier stages of the disease. The combination of such biomarkers assessed by multiple modalities commonly improves the likelihood of AD etiology. We aimed to explore the discriminative ability of Aβ PET features and whether combining Aβ PET and structural MRI features can improve the classification performance of the machine learning model in older healthy control (OHC) and mild cognitive impairment (MCI) from AD.

Effects of nurse-led brief behavioral treatment for insomnia in adults: a randomized controlled trial.

Study Objectives: We examined the effects of nurse-led brief behavioral treatment for insomnia (BBTI) on insomnia severity, sleep status, daytime function, quality of life, psychological distress levels, treatment response, and insomnia remission in young and middle-aged Asian adults with insomnia symptoms.

Methods: This 2-parallel, randomized controlled trial recruited 42 participants with insomnia symptoms randomly allocated to the nurse-led BBTI group or sleep hygiene group. The outcome measurements included the Insomnia Severity Index, sleep diary, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Brief Fatigue Inventory, RAND-36 Health Status Inventory, and the Depression, Anxiety, and Stress Scale-21.

Spiritual Interventions Among Pediatric Patients With Cancer: A Systematic Review And Meta-Analysis.

Context: Although spiritual intervention is crucial in the care of childhood cancer patients (CCPs), its effectiveness has not yet been systematically evaluated.

Objectives: To determine the effectiveness of existing spiritual interventions on psychological, spiritual outcomes, and quality of life (QoL) in CCPs.

Methods: We searched eight databases to identify relevant randomized controlled trials and quasi-experimental studies.

Randomized Secondary Prevention Trials in Participants With Symptomatic Intracranial Atherosclerotic Stenosis.

Intracranial atherosclerotic stenosis is a prevalent cause of ischemic stroke worldwide. Its association with silent cerebral infarcts and its contribution to cognitive impairment and dementia emphasize the critical need for disease prevention and effective management strategies. Despite extensive research on secondary stroke prevention treatment over the past several decades, intracranial atherosclerotic stenosis continues to exhibit a notably higher recurrent stroke rate compared with other causes.

Endoplasmic Reticulum Protein 72 Regulates Integrin Mac-1 Activity to Influence Neutrophil Recruitment.

Background: Integrins mediate the adhesion, crawling, and migration of neutrophils during vascular inflammation. Thiol exchange is important in the regulation of integrin functions. ERp72 (endoplasmic reticulum-resident protein 72) is a member of the thiol isomerase family responsible for the catalysis of disulfide rearrangement.

Somatic Mosaicism in Variant Correlates With Stereoelectroencephalography-Derived Electrophysiology.

Objectives: Brain-limited pathogenic somatic variants are associated with focal pediatric epilepsy, but reliance on resected brain tissue samples has limited our ability to correlate epileptiform activity with abnormal molecular pathology. We aimed to identify the pathogenic variant and map variant allele fractions (VAFs) across an abnormal region of epileptogenic brain in a patient who underwent stereoelectroencephalography (sEEG) and subsequent motor-sparing left frontal disconnection.

Methods: We extracted genomic DNA from peripheral blood, brain tissue resected from peri-sEEG electrode regions, and microbulk brain tissue adherent to sEEG electrodes.

Pilot-scale production of inactivated monoglycosylated split HN influenza virus vaccine provides cross-strain protection against influenza viruses.

Influenza epidemics and pandemics caused by newly emerging virus strains highlight an urgent need to develop a universal vaccine against viruses. Previously, a monoglycosylated X-181 vaccine demonstrated that the HA possessing a single N-acetylglucosamine at each N-glycosylation site is superior to confer broader protection in mice than conventional vaccines. However, the greatest challenge in conducting clinical trials is the need to develop robust manufacturing processes capable of producing vaccines at the pilot scale with the desired stability, potency, and efficacy.

Endothelial Yin Yang 1 Phosphorylation at S118 Induces Atherosclerosis Under Flow.

Rationale: Disturbed flow occurring in arterial branches and curvatures induces vascular endothelial cell (EC) dysfunction and atherosclerosis. We postulated that disturbed flow plays important role in modulating phosphoprotein expression profiles to regulate endothelial functions and atherogenesis.

Objective: The goal of this study is to discover novel site-specific phosphorylation alterations induced by disturbed flow in ECs to contribute to atherosclerosis.

Altered Cardiac Energetics and Mitochondrial Dysfunction in Hypertrophic Cardiomyopathy.

Background: Hypertrophic cardiomyopathy (HCM) is a complex disease partly explained by the effects of individual gene variants on sarcomeric protein biomechanics. At the cellular level, HCM mutations most commonly enhance force production, leading to higher energy demands. Despite significant advances in elucidating sarcomeric structure-function relationships, there is still much to be learned about the mechanisms that link altered cardiac energetics to HCM phenotypes.

Therapeutic Inhibition of Acid-Sensing Ion Channel 1a Recovers Heart Function After Ischemia-Reperfusion Injury.

Background: Ischemia-reperfusion injury (IRI) is one of the major risk factors implicated in morbidity and mortality associated with cardiovascular disease. During cardiac ischemia, the buildup of acidic metabolites results in decreased intracellular and extracellular pH, which can reach as low as 6.0 to 6.

Vegetarian diet and incidence of total, ischemic, and hemorrhagic stroke in 2 cohorts in Taiwan.

Objective: To determine how a vegetarian diet affects stroke incidence in 2 prospective cohorts and to explore whether the association is modified by dietary vitamin B intake.

Methods: Participants without stroke in the Tzu Chi Health Study (cohort 1, n = 5,050, recruited in 2007-2009) and the Tzu Chi Vegetarian Study (cohort 2, n = 8,302, recruited in 2005) were followed until the end of 2014. Diet was assessed through food frequency questionnaires in both cohorts at baseline.

Aldosterone-producing Adenoma in Primary Aldosteronism: CT-guided Radiofrequency Ablation-Long-term Results and Recurrence Rate.

Purpose To evaluate the long-term biochemical, clinical, and recurrence outcomes of radiofrequency (RF) ablation in treating primary aldosteronism due to aldosterone-producing adenoma (APA). Materials and Methods Institutional review board approval and written informed consent were obtained. The use of computed tomographically (CT) guided percutaneous RF ablation was evaluated in 36 patients (19 men; mean age ± standard deviation, 52.

Three important amino acids control the regioselectivity of flavonoid glucosidation in glycosyltransferase-1 from Bacillus cereus.

Glycosyltransferase-1 from Bacillus cereus (BcGT1) catalyzes a reaction that transfers a glucosyl moiety to flavonoids, such as quercetin, kaempferol, and myricetin. The enzymatic glucosidation shows a broad substrate specificity when the reaction is catalyzed by wild-type BcGT1. Preliminary assays demonstrated that the F240A mutant significantly improves the regioselectivity of enzymatic glucosidation toward quercetin.

The Differential Levels of Inflammatory Cytokines and BDNF among Bipolar Spectrum Disorders.

Objective: Emerging evidence suggests that inflammation and neurodegeneration underlies bipolar disorder. To investigate biological markers of cytokines and brain-derived neurotrophic factor between bipolar I, bipolar II, and other specified bipolar disorder with short duration hypomania may support the association with inflammatory dysregulation and bipolar disorder and, more specifically, provide evidence for other specified bipolar disorder with short duration hypomania patients were similar to bipolar II disorder patients from a biological marker perspective.

Methods: We enrolled patients with bipolar I disorder (n=234), bipolar II disorder (n=260), other specified bipolar disorder with short duration hypomania (n=243), and healthy controls (n=140).

Hyperglycemia-induced secretion of endothelial heparanase stimulates a vascular endothelial growth factor autocrine network in cardiomyocytes that promotes recruitment of lipoprotein lipase.

Objective: During diabetes mellitus, coronary lipoprotein lipase increases to promote the predominant use of fatty acids. We have reported that high glucose stimulates active heparanase secretion from endothelial cells to cleave cardiomyocyte heparan sulfate and release bound lipoprotein lipase for transfer to the vascular lumen. In the current study, we examined whether heparanase also has a function to release cardiomyocyte vascular endothelial growth factor (VEGF), and whether this growth factor influences cardiomyocyte fatty acid delivery in an autocrine manner.