A revamped rat reference genome improves the discovery of genetic diversity in laboratory rats.

The seventh iteration of the reference genome assembly for -mRatBN7.2-corrects numerous misplaced segments and reduces base-level errors by approximately 9-fold and increases contiguity by 290-fold compared to its predecessor. Gene annotations are now more complete, significantly improving the mapping precision of genomic, transcriptomic, and proteomics data sets.

The association of intensive blood pressure treatment and non-fatal cardiovascular or serious adverse events in older adults with mortality: mediation analysis in SPRINT.

Aims: Randomized clinical trials of hypertension treatment intensity evaluate the effects on incident major adverse cardiovascular events (MACEs) and serious adverse events (SAEs). Occurrences after a non-fatal index event have not been rigorously evaluated. The aim of this study was to evaluate the association of intensive (<120 mmHg) to standard (<140 mmHg) blood pressure (BP) treatment with mortality mediated through a non-fatal MACE or non-fatal SAE in 9361 participants in the Systolic Blood Pressure Intervention Trial.

Obesity Modifies the Relationship Between Raltegravir and Dolutegravir Hair Concentrations and Body Weight Gain in Women Living with HIV.

Integrase strand-transfer inhibitors (INSTIs) are associated with weight gain in women living with HIV (WLH). Relationships between drug exposure, baseline obesity, and INSTI-associated weight gain remain unclear. Data from 2006 to 2016 were analyzed from virally suppressed WLH enrolled in the Women's Interagency HIV Study, who switched/added an INSTI to antiretroviral therapy: [raltegravir (RAL), dolutegravir (DTG), or elvitegravir (EVG)].

Antithrombin, Protein C, and Protein S: Genome and Transcriptome-Wide Association Studies Identify 7 Novel Loci Regulating Plasma Levels.

Background: Antithrombin, PC (protein C), and PS (protein S) are circulating natural anticoagulant proteins that regulate hemostasis and of which partial deficiencies are causes of venous thromboembolism. Previous genetic association studies involving antithrombin, PC, and PS were limited by modest sample sizes or by being restricted to candidate genes. In the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, we meta-analyzed across ancestries the results from 10 genome-wide association studies of plasma levels of antithrombin, PC, PS free, and PS total.

Effect of Material and Pad Abrasion on Shear Bond Strength of 3D-Printed Orthodontic Brackets.

Objective: To investigate the effect of printing material and air abrasion of bracket pads on the shear bond strength of 3D-printed plastic orthodontic brackets when bonded to the enamel of extracted human teeth.

Materials And Methods: Premolar brackets were 3D-printed using the design of a commercially available plastic bracket in two biocompatible resins: Dental LT Resin and Dental SG Resin (n = 40/material). 3D-printed brackets and commercially manufactured plastic brackets were divided into two groups (n = 20/group), one of which was air abraded.

Overcoming adaptive resistance to anti-VEGF therapy by targeting CD5L.

Antiangiogenic treatment targeting the vascular endothelial growth factor (VEGF) pathway is a powerful tool to combat tumor growth and progression; however, drug resistance frequently emerges. We identify CD5L (CD5 antigen-like precursor) as an important gene upregulated in response to antiangiogenic therapy leading to the emergence of adaptive resistance. By using both an RNA-aptamer and a monoclonal antibody targeting CD5L, we are able to abate the pro-angiogenic effects of CD5L overexpression in both in vitro and in vivo settings.

Aryl hydrocarbon receptor maintains hepatic mitochondrial homeostasis in mice.

Objective: Mitophagy removes damaged mitochondria to maintain cellular homeostasis. Aryl hydrocarbon receptor (AhR) expression in the liver plays a crucial role in supporting normal liver functions, but its impact on mitochondrial function is unclear. Here, we identified a new role of AhR in the regulation of mitophagy to control hepatic energy homeostasis.

Whole Genome Analysis of Venous Thromboembolism: the Trans-Omics for Precision Medicine Program.

Background: Risk for venous thromboembolism has a strong genetic component. Whole genome sequencing from the TOPMed program (Trans-Omics for Precision Medicine) allowed us to look for new associations, particularly rare variants missed by standard genome-wide association studies.

Methods: The 3793 cases and 7834 controls (11.

Ethanol-paired conditioned stimulus effects on concurrent reinforced responding for ethanol and food.

The influence of Pavlovian Conditioned Stimuli (CS) on ethanol self-administration and choice between ethanol and an alternative are potentially important. Ethanol-paired CS might increase ethanol self-administration, especially when it has been reduced during recovery, though the selectivity of these increases has been questioned. To date, one study examined the effects of an ethanol-paired CS on ethanol choice and found that the CS increased ethanol-responding more than food-responding when both were in extinction.

Identification of microbiological factors associated with periodontal health disparities.

The present study aimed at identifying risk factors associated with periodontitis development and periodontal health disparities with emphasis on differential oral microbiota. The prevalence of periodontitis is recently rising dentate adults in the US, which presents a challenge to oral health and overall health. The risk of developing periodontitis is higher in African Americans (AAs), and Hispanic Americans (HAs) than in Caucasian Americans (CAs).

Sex Differences in Vascular Response to Mental Stress and Adverse Cardiovascular Events Among Patients With Ischemic Heart Disease.

Background: Microvascular measures of vascular dysfunction during acute mental stress may be important determinants of major adverse cardiovascular events (MACE), especially among younger and middle-aged women survivors of an acute myocardial infarction.

Methods: In the MIMS2 study (Myocardial Infarction and Mental Stress 2), individuals who had been hospitalized for a myocardial infarction in the past 8 months were prospectively followed for 5 years. MACE was defined as a composite index of cardiovascular death and first/recurring events for nonfatal myocardial infarction and hospitalizations for heart failure.

Neoadjuvant-Adjuvant or Adjuvant-Only Pembrolizumab in Advanced Melanoma.

Background: Whether pembrolizumab given both before surgery (neoadjuvant therapy) and after surgery (adjuvant therapy), as compared with pembrolizumab given as adjuvant therapy alone, would increase event-free survival among patients with resectable stage III or IV melanoma is unknown.

Methods: In a phase 2 trial, we randomly assigned patients with clinically detectable, measurable stage IIIB to IVC melanoma that was amenable to surgical resection to three doses of neoadjuvant pembrolizumab, surgery, and 15 doses of adjuvant pembrolizumab (neoadjuvant-adjuvant group) or to surgery followed by pembrolizumab (200 mg intravenously every 3 weeks for a total of 18 doses) for approximately 1 year or until disease recurred or unacceptable toxic effects developed (adjuvant-only group). The primary end point was event-free survival in the intention-to-treat population.

Burden of fatty liver and hepatic fibrosis in persons with HIV: A diverse cross-sectional US multicenter study.

Background Aims: The current prevalence of fatty liver disease (FLD) due to alcohol-associated (AFLD) and nonalcoholic (NAFLD) origins in US persons with HIV (PWH) is not well defined. We prospectively evaluated the burden of FLD and hepatic fibrosis in a diverse cohort of PWH.

Approach Results: Consenting participants in outpatient HIV clinics in 3 centers in the US underwent detailed phenotyping, including liver ultrasound and vibration-controlled transient elastography for controlled attenuation parameter and liver stiffness measurement.

Constraints of vigilance-dependent noradrenergic signaling to mouse cerebellar Bergmann glia.

Behavioral state plays an important role in determining astroglia Ca signaling. In particular, locomotion-mediated elevated vigilance has been found to trigger norepinephrine-dependent whole cell Ca elevations in astroglia throughout the brain. For cerebellar Bergmann glia it has recently been found that locomotion-induced transient Ca elevations depend on their α -adrenergic receptors.

Non-alcoholic fatty liver disease is not associated with impairment in health-related quality of life in virally suppressed persons with human immune deficiency virus.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in persons with HIV (PWH) (HIV-NAFLD). It is unknown if HIV-NAFLD is associated with impairment in health-related quality of life (HRQOL). We examined HRQOL in PWH with and without NAFLD, compared HRQOL in HIV- versus primary NAFLD, and determined factors associated with HRQOL in these groups.

Percutaneous revascularization for the treatment of refractory digital ischemia in systemic sclerosis.

Objective: The objective of this study is to explore the role of adjunctive percutaneous revascularization of the hand in the management of patients with systemic sclerosis-associated refractory digital ischemia.

Methods: We present our initial experience of using percutaneous upper extremity interventions to treat patients with systemic sclerosis and symptomatic Raynaud's phenomenon who presented with either refractory digital ischemia or non-healing ulcers. We discuss patient characteristics, procedural findings, and short-term clinical outcomes of these interventions.

Cover with caution: Management of the Left Subclavian Artery in TEVAR for trauma.

Background: Elective Thoracic Endovascular Aortic Repair (TEVAR) with left subclavian artery coverage (LSA-C) without revascularization is associated with increased rates of ischemic stroke. In patients with blunt thoracic aortic injury (BTAI) requiring TEVAR, LSA-C is frequently required in over one-third of patients. This study aimed to evaluate outcomes of TEVAR in BTAI patients with and without LSA-C.

General anesthesia vs procedural sedation for failed NeuroThrombectomy undergoing rescue stenting: intention to treat analysis.

Background: There is little data available to guide optimal anesthesia management during rescue intracranial angioplasty and stenting (ICAS) for failed mechanical thrombectomy (MT). We sought to compare the procedural safety and functional outcomes of patients undergoing rescue ICAS for failed MT under general anesthesia (GA) vs non-general anesthesia (non-GA).

Methods: We searched the data from the Stenting and Angioplasty In Neuro Thrombectomy (SAINT) study.

A Case of Successful Treatment of Recurrent Urinary Tract Infection by Extended-Spectrum β-Lactamase Producing Using Oral Lyophilized Fecal Microbiota Transplant.

Recurrent urinary tract infections (UTIs) are a challenging clinical entity that can be frustrating for patient and physician alike. Repeated rounds of antibiotics can select for multidrug-resistant organisms, further complicating care. We describe the successful use of fecal microbiota transplantation (FMT) for the treatment of recurrent extended-spectrum β-lactamase (ESBL)-producing UTIs in a patient with an ileal conduit and urostomy.

Reduced alcohol use increases drink-refusal self-efficacy: Evidence from a contingency management study for DWI arrestees.

Background: Several therapies and interventions to reduce drinking first target drink-refusal self-efficacy (DRSE) to influence drinking behavior. While higher self-efficacy scores are correlated with better outcomes, it is unclear that increased self-efficacy is the causative step leading to improved outcomes. Instead, this correlation may result from reduced drinking that increased self-efficacy.

Somatic Variants in SVIL in Cerebral Aneurysms.

Background And Objectives: While somatic mutations have been well-studied in cancer, their roles in other complex traits are much less understood. Our goal is to identify somatic variants that may contribute to the formation of saccular cerebral aneurysms.

Methods: We performed whole-exome sequencing on aneurysm tissues and paired peripheral blood.