Genomics yields biological and phenotypic insights into bipolar disorder.

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

Exploring Integrin α5β1 as a Potential Therapeutic Target for Pulmonary Arterial Hypertension: Insights From Comprehensive Multicenter Preclinical Studies.

Background: Pulmonary arterial hypertension (PAH) is characterized by obliterative vascular remodeling of the small pulmonary arteries (PAs) and progressive increase in pulmonary vascular resistance leading to right ventricular failure. Although several drugs are approved for the treatment of PAH, mortality rates remain high. Accumulating evidence supports a pathological function of integrins in vessel remodeling, which are gaining renewed interest as drug targets.

Impact of Heart Transplant Allocation Changes on Waitlist Mortality and Clinical Practice in Pediatric and Adult Patients With Congenital Heart Disease and Cardiomyopathy.

Background: The United Network of Organ Sharing made changes to the priority for allocation of hearts for transplantation (HT) in 2016 for pediatric patients and 2018 for adult patients. Although recent work has evaluated the impact of the revised allocation systems on mechanical circulatory support practices and waitlist outcomes, there are limited data that focus more specifically on the impact of the allocation changes on patients with congenital heart disease (CHD) or cardiomyopathy and how these relationships might differ in pediatric and adult patients.

Methods: The United Network of Organ Sharing database was queried for pediatric (<18 years of age) and adult (18-50 years of age) patients with a CHD or cardiomyopathy diagnosis listed for HT.

Deficiency of Endothelial Impairs Pulmonary Vascular Angiogenesis and Predisposes Pulmonary Hypertension.

Background: Mechanosensitive Piezo1 channel plays a key role in pulmonary hypertension (PH). However, the role of Piezo2 in PH remains unclear.

Methods: Endothelial cell (EC)-specific knockout (, Tek-Cre; ) rats and primarily cultured pulmonary microvascular ECs were used to determine the role of Piezo2 in PH.

Global Fatty Degeneration Index on Preoperative Magnetic Resonance Imaging Predicts Early Postoperative Shoulder Stiffness at 3 Months After Primary Rotator Cuff Repair.

Purpose: To determine whether the fatty infiltration of rotator cuff muscles, as measured by magnetic resonance imaging (MRI) preoperatively and assessed using the Goutallier fatty degeneration index (GFDI), can predict early postoperative shoulder stiffness (POSS) after rotator cuff repair (RCR).

Methods: This retrospective longitudinal cohort study included patients who underwent primary RCR, had available medical records, and underwent MRI before RCR between November 2012 and July 2022. Patients were excluded on the basis of the following criteria: (1) preoperative shoulder stiffness, (2) additional procedures (e.

Accurate Intramyocardial Hemorrhage Assessment with Fast, Free-running, Cardiac Quantitative Susceptibility Mapping.

Purpose To evaluate the performance of a high-dynamic-range quantitative susceptibility mapping (HDR-QSM) cardiac MRI technique to detect intramyocardial hemorrhage (IMH) and quantify iron content using phantom and canine models. Materials and Methods A free-running whole-heart HDR-QSM technique for IMH assessment was developed and evaluated in calibrated iron phantoms and 14 IMH female canine models. IMH detection and iron content quantification performance of this technique was compared with the conventional iron imaging approaches, R2*(1/T2*) maps, using measurements from ex vivo imaging as the reference standard.

Development and Validation of a Contrast-Enhanced US VI-RADS for Evaluating Muscle Invasion in Bladder Cancer.

Background Contrast-enhanced US (CEUS) can be used preoperatively for evaluating muscle invasion in bladder cancer, which is important for determining appropriate treatment. However, diagnostic criteria for assessing this at CEUS have not been standardized. Purpose To develop and validate a CEUS Vesical Imaging Reporting and Data System (VI-RADS) for evaluating muscle invasion in bladder cancer.

The influence of CLEC5A on early macrophage-mediated inflammation in COPD progression.

Chronic obstructive pulmonary disease (COPD) is a complex syndrome with poorly understood mechanisms driving its early progression (GOLD stages 1-2). Elucidating the genetic factors that influence early-stage COPD, particularly those related to airway inflammation and remodeling, is crucial. This study analyzed lung tissue sequencing data from patients with early-stage COPD (GSE47460) and smoke-exposed mice.

Quality of Life and Exercise Capacity in Early Stage and Subclinical Hypertrophic Cardiomyopathy: A Secondary Analysis of the VANISH Trial.

Background: The health-related quality of life (HRQOL) and cardiopulmonary exercise testing (CPET) performance of individuals with subclinical and early stage hypertrophic cardiomyopathy (HCM) have not been systematically studied. Improved understanding will inform the natural history of HCM and factors influencing well-being.

Methods: VANISH trial (Valsartan for Attenuating Disease Evolution in Early Sarcomeric HCM) participants with early stage sarcomeric HCM (primary analysis cohort) and subclinical HCM (sarcomere variant without left ventricular hypertrophy comprising the exploratory cohort) who completed baseline and year 2 HRQOL assessment via the pediatric quality of life inventory and CPET were studied.

Findings of an Extraluminal Leiomyosarcoma of the Urinary Bladder in a Dog.

A 9 yr old male miniature poodle presented with acute diarrhea, vomiting, and a distended abdomen. A large and firm mass was palpated in the caudal abdomen. Radiography showed a large soft-tissue mass in the mid ventral abdomen.

Large Animal Translational Validation of 3 Mitral Valve Repair Operations for Mitral Regurgitation Using a Mitral Valve Prolapse Model: A Comprehensive In Vivo Biomechanical Engineering Analysis.

Background: Various mitral repair techniques have been described. Though these repair techniques can be highly effective when performed correctly in suitable patients, limited quantitative biomechanical data are available. Validation and thorough biomechanical evaluation of these repair techniques from translational large animal in vivo studies in a standardized, translatable fashion are lacking.

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.

Enhanced rare-earth separation with a metal-sensitive lanmodulin dimer.

Technologically critical rare-earth elements are notoriously difficult to separate, owing to their subtle differences in ionic radius and coordination number. The natural lanthanide-binding protein lanmodulin (LanM) is a sustainable alternative to conventional solvent-extraction-based separation. Here we characterize a new LanM, from Hansschlegelia quercus (Hans-LanM), with an oligomeric state sensitive to rare-earth ionic radius, the lanthanum(III)-induced dimer being >100-fold tighter than the dysprosium(III)-induced dimer.

LTBP4 Protects Against Renal Fibrosis via Mitochondrial and Vascular Impacts.

Background: As a part of natural disease progression, acute kidney injury (AKI) can develop into chronic kidney disease via renal fibrosis and inflammation. LTBP4 (latent transforming growth factor beta binding protein 4) regulates transforming growth factor beta, which plays a role in renal fibrosis pathogenesis. We previously investigated the role of LTBP4 in chronic kidney disease.

Association of 4qA-Specific Distal D4Z4 Hypomethylation With Disease Severity and Progression in Facioscapulohumeral Muscular Dystrophy.

Background And Objectives: The objective of this study was to examine whether the regional methylation levels at the most distal D4Z4 repeat units (RU) in the 4qA-permissive haplotype were associated with disease severity and progression in facioscapulohumeral muscular dystrophy type 1 (FSHD1).

Methods: This 21-year, retrospective, observational cohort study was conducted at the Fujian Neuromedical Center (FNMC) in China. Methylation levels of the most distal D4Z4 RU, including 10 CpGs, were assessed in all participants by bisulfite sequencing.

A Retrospective Study of the Safety and Immunogenicity of MVC-COV1901 Vaccine for People Living with HIV.

Background: This study aimed to assess the safety and immunogenicity of MVC-COV1901, a recombinant COVID-19 protein vaccine, containing S-2P protein adjuvanted with CpG 1018 and aluminum hydroxide, for people living with HIV (PWH).

Methods: A total of 57 PWH of ≥20 years of age who are on stable antiretroviral therapy were compared with 882 HIV-negative participants. Participants received two doses of MVC-COV1901 28 days apart.

Effect of a Novel E3 Probiotics Formula on the Gut Microbiome in Atopic Dermatitis Patients: A Pilot Study.

Atopic dermatitis (AD) has been shown to be closely related to gut dysbiosis mediated through the gut−skin axis, and thus the gut microbiome has recently been explored as a potential therapeutic target for the treatment of AD. Contrasting and varying efficacy have been reported since then. In order to investigate the determining factor of probiotics responsiveness in individuals with AD, we initiated the analysis of 41 AD patients with varying disease severity in Hong Kong, whereas the severity was assessed by Eczema Area and Severity Index (EASI) by board certified dermatologist.

Fast-tracking antibody maturation using a B cell-based display system.

Affinity maturation, an essential component of antibody engineering, is crucial for developing therapeutic antibodies. Cell display system coupled with somatic hypermutation (SHM) initiated by activation-induced cytidine deaminase (AID) is a commonly used technique for affinity maturation. AID introduces targeted DNA lesions into hotspots of immunoglobulin (Ig) gene loci followed by erroneous DNA repair, leading to biased mutations in the complementary determining regions.

Stroke genetics informs drug discovery and risk prediction across ancestries.

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.

Scalable anisotropic cooling aerogels by additive freeze-casting.

Cooling in buildings is vital to human well-being but inevitability consumes significant energy, adding pressure on achieving carbon neutrality. Thermally superinsulating aerogels are promising to isolate the heat for more energy-efficient cooling. However, most aerogels tend to absorb the sunlight for unwanted solar heat gain, and it is challenging to scale up the aerogel fabrication while maintaining consistent properties.