Genome-wide association study of varenicline-aided smoking cessation.

Introduction: Varenicline is an α4β2 nicotinic acetylcholine receptor partial agonist with the highest therapeutic efficacy of any pharmacological smoking cessation aid and a 12-month cessation rate of 26%. Genetic variation may be associated with varenicline response, but to date no genome-wide association studies of varenicline response have been published.

Methods: In this study, we investigated the genetic contribution to varenicline effectiveness using two electronic health record-derived phenotypes.

Triptolide exhibits dual anti-tumor effects through inhibiting autophagy and extracellular matrix activation in pancreatic cancer.

Aim: The tumor microenvironment in pancreatic cancer, characterized by abundant desmoplastic stroma, has been implicated in the failure of chemotherapy. Therefore, developing therapeutic strategies targeting tumor and stromal cells is essential. Triptolide, a natural compound derived from the plant Tripterygium wilfordii, has shown antitumor activity in various cancers, including pancreatic cancer.

Use of and Steering to Pharmacies Owned by Insurers and Pharmacy Benefit Managers in Medicare.

Importance: The prevalence of pharmacies owned by integrated insurers and pharmacy benefit managers (PBMs), or insurer-PBMs, is of growing regulatory concern. However, little is known about the role of these pharmacies in Medicare, in which pharmacy network protections may influence market dynamics.

Objective: To evaluate the prevalence of insurer-PBM-owned pharmacies and the extent to which insurer-PBMs steer patients to pharmacies they own in Medicare.

Repetitive Transcranial Magnetic Stimulation and Tai Chi Chuan for Older Adults With Sleep Disorders and Mild Cognitive Impairment: A Randomized Clinical Trial.

Importance: Sleep disorders and mild cognitive impairment (MCI) commonly coexist in older adults, increasing their risk of developing dementia. Long-term tai chi chuan has been proven to improve sleep quality in older adults. However, their adherence to extended training regimens can be challenging.

Radon Exposure and Gestational Diabetes.

Importance: Understanding environmental risk factors for gestational diabetes (GD) is crucial for developing preventive strategies and improving pregnancy outcomes.

Objective: To examine the association of county-level radon exposure with GD risk in pregnant individuals.

Design, Setting, And Participants: This multicenter, population-based cohort study used data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b) cohort, which recruited nulliparous pregnant participants from 8 US clinical centers between October 2010 and September 2013.

Repurposing Licensed Drugs with Activity Against Epstein-Barr Virus for Treatment of Multiple Sclerosis: A Systematic Approach.

Background: Epstein-Barr virus (EBV) is implicated as a necessary factor in the development of multiple sclerosis (MS) and may also be a driver of disease activity. Although it is not clear whether ongoing viral replication is the driver for MS pathology, MS researchers have considered the prospect of using drugs with potential efficacy against EBV in the treatment of MS. We have undertaken scientific and lived experience expert panel reviews to shortlist existing licensed therapies that could be used in later-stage clinical trials in MS.

Heart failure outcomes captured by adverse event reporting in participants with type 2 diabetes and atherosclerotic cardiovascular disease: Observations from the VERTIS CV trial.

Aims: In VERTIS CV, ertugliflozin was associated with a 30% risk reduction for adjudication-confirmed, first and total hospitalizations for heart failure (HHF) in participants with type 2 diabetes and atherosclerotic cardiovascular disease. We evaluated the impact of ertugliflozin on the broader spectrum of all reported heart failure (HF) events independent of adjudication confirmation.

Methods And Results: Data from participants who received ertugliflozin (5 or 15 mg) were pooled and compared versus placebo.

Do you know your PSMA-tracer? Variability in the biodistribution of different PSMA ligands and its potential impact on defining PSMA-positivity prior to PSMA-targeted therapy.

Background: In clinical practice, several radiopharmaceuticals are used for PSMA-PET imaging, each with distinct biodistribution patterns. This may impact treatment decisions and outcomes, as eligibility for PSMA-directed radioligand therapy is usually assessed by comparing tumoral uptake to normal liver uptake as a reference. In this study, we aimed to compare tracer uptake intraindividually in various reference regions including liver, parotid gland and spleen as well as the respective tumor-to-background ratios (TBR) of different F-labeled PSMA ligands to today's standard radiopharmaceutical Ga-PSMA-11 in a series of patients with biochemical recurrence of prostate cancer who underwent a dual PSMA-PET examination as part of an individualized diagnostic approach.

Development of a brief screening measure of unmet supportive care needs (SCNS-P&C-6) in caregivers of people with high-grade glioma.

Purpose: Informal caregivers of people with high grade glioma (HGG) often have high levels of unmet support needs. Routine screening for unmet needs can facilitate appropriate and timely access to supportive care. We aimed to develop a brief screening tool for HGG caregiver unmet needs, based on the Supportive Care Needs Survey-Partners & Caregivers (SCNS-P&C).

Molecular Epidemiology and Clinical Aspects of Dermatophytosis in Guiyang, Southwest China (2017-2023): A Single-Institution Retrospective Study.

Epidemiological studies combining taxonomic and clinical data have been limited globally, particularly Guiyang, the most under-developed economic provincial capital city in southwestern China. A retrospective analysis was performed of dermatophyte epidemiology involving all culture-positive cases received between May 2017 and May 2023 at the Affiliated Hospital of Guizhou Medical University. Phylogenetic analysis was conducted on 391 dermatophyte isolates collected from patients using the rDNA internal transcribed spacer sequences.

"It's more than a ride" veteran perceptions of peer specialist qualities and activities that were most valuable for post-incarceration reentry: a qualitative analysis.

Background: Reentry veterans experience many barriers to achieving physical and psychological well-being. While peer specialists can provide important support to veterans as they readjust to life post-incarceration, their specific activities and qualities most valued by veterans are not well known. The Post-Incarceration Engagement (PIE) intervention, coordinated with VA's Health Care for Reentry Veterans (HCRV) program, links reentry veterans with a peer specialist who provides connection to services and social-emotional support during the reentry process.

Long-term mitochondrial and metabolic impairment in lymphocytes of subjects who recovered after severe COVID-19.

The underlying mechanisms explaining the differential course of SARS-CoV-2 infection and the potential clinical consequences after COVID-19 resolution have not been fully elucidated. As a dysregulated mitochondrial activity could impair the immune response, we explored long-lasting changes in mitochondrial functionality, circulating cytokine levels, and metabolomic profiles of infected individuals after symptoms resolution, to evaluate whether a complete recovery could be achieved. Results of this pilot study evidenced that different parameters of aerobic respiration in lymphocytes of individuals recuperated from a severe course lagged behind those shown upon mild COVID-19 recovery, in basal conditions and after simulated reinfection, and they also showed altered glycolytic capacity.

Sacubitril/valsartan versus valsartan initiation in patients naïve to renin-angiotensin system inhibitors: Insights from PARAGLIDE-HF.

Aims: Whether prior treatment with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) modifies efficacy and safety of sacubitril/valsartan (Sac/Val) in patients with heart failure (HF) and ejection fraction (EF) >40% is unclear, thus Sac/Val according to ACEi/ARB status at baseline was assessed.

Methods And Results: This was a pre-specified analysis of Prospective comparison of ARNI with ARB Given following stabiLization In DEcompensated HFpEF (PARAGLIDE-HF), a double-blind, randomized controlled trial of Sac/Val versus valsartan, categorizing patients according to baseline ACEi/ARB status. The primary endpoint was time-averaged proportional change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) from baseline through weeks 4 and 8.

Hantaan virus glycoprotein Gc induces NEDD4-dependent PTEN ubiquitination and degradation to escape the restriction of autophagosomes and facilitate viral propagation.

Hantaan virus (HTNV) infection causes severe hemorrhagic fever with renal syndrome (HFRS) in humans and the infectious process can be regulated by autophagy. The phosphatase and tensin homolog (PTEN) protein has antiviral effects and plays a critical role in the autophagy pathway. However, the relationship between PTEN and HTNV infection is not clear and whether PTEN-regulated autophagy involves in HTNV replication is unknown.

Organ-specific malperfusion in acute type A aortic dissection: epidemiological meta-analysis of incidence rates.

Background: Acute type A aortic dissection is a life-threatening clinical emergency that necessitates immediate surgical intervention with an estimated mortality rate of approximately 1-2% per hour. When complicated by malperfusion, the perioperative mortality rate is reported to be increased by up to 39%. Malperfusion can affect many vascular beds with varying incidence and severity, resulting in coronary, cerebral, visceral, peripheral, renal or spinal malperfusion.

Digital Profiling of Tumor Extracellular Vesicle-Associated RNAs Directly from Unprocessed Blood Plasma.

Tumor-derived extracellular vesicle (tEV)-associated RNAs hold promise as diagnostic biomarkers, but their clinical use is hindered by the rarity of tEVs among nontumor EVs. Here, we present EV-CLIP, a highly sensitive droplet-based digital method for profiling EV RNA. EV-CLIP utilizes the fusion of EVs with charged liposomes (CLIPs) in a microfluidic chip.

Histological staining of tick bite skin biopsies for spirochetes and Powassan virus RNA.

is a vector of several human pathogens in the United States, including the cause of Lyme disease, and Powassan virus (POWV), an emerging cause of severe encephalitis. Skin biopsies from tick bite sites are frequently collected and tested for the presence of spirochetes ( spp.), which remain elusive.

Windows in the ICU and Postoperative Delirium: A Retrospective Cohort Study.

Objectives: The ICU built environment-including the presence of windows-has long been thought to play a role in delirium. This study investigated the association between the presence or absence of windows in patient rooms and ICU delirium.

Design: Retrospective single institution cohort study.

Uncovering Antiviral Potential of Cistus ladanifer Extracts Against HSV-1 and SARS-CoV-2 by In Vitro and In Silico Analysis.

Infectious diseases remain a major global health concern. Cistus ladanifer, a plant commonly employed in Moroccan traditional medicine, has been identified as a potential antiviral candidate. This study aimed to evaluate the antiviral activity of C.

How Does Diploic Space Thickness Change With Age?

Background: Cranial defects from trauma, surgery, or congenital conditions require precise reconstruction to restore cranial vault integrity. Autogenous calvarial grafts are preferred for their histocompatibility and biomechanical properties, but their success depends on a well-developed diploic space. Although prior studies have described overall skull thickness development, less is known about how diploic thickness changes through adulthood.

Closed genomes of commercial inoculant rhizobia provide a blueprint for management of legume inoculation.

Unlabelled: Rhizobia are soil bacteria capable of establishing symbiosis within legume root nodules, where they reduce atmospheric N into ammonia and supply it to the plant for growth. Australian soils often lack rhizobia compatible with introduced agricultural legumes, so inoculation with exotic strains has become a common practice for over 50 years. While extensive research has assessed the N-fixing capabilities of these inoculants, their genomics, taxonomy, and core and accessory gene phylogeny are poorly characterized.