Joint modeling of human cortical structure: Genetic correlation network and composite-trait genetic correlation.

Heritability and genetic covariance/correlation quantify the marginal and shared genetic effects across traits. They offer insights on the genetic architecture of complex traits and diseases. To explore how genetic variations contribute to brain function variations, we estimated heritability and genetic correlation across cortical thickness, surface area, and volume of 33 anatomically predefined regions in left and right hemispheres, using summary statistics of genome-wide association analyses of 31,968 participants in the UK Biobank. To characterize the relationships between these regions of interest, we constructed a genetic network for these regions using recursive two-way cut-offs in similarity matrices defined by genetic correlations. The inferred genetic network matches the brain lobe mapping more closely than the network inferred from phenotypic similarities. We further studied the associations between the genetic network for brain regions and 30 complex traits through a novel composite-linkage disequilibrium score regression method. We identified seven significant pairs, which offer insights on the genetic basis for regions of interest mediated by cortical measures.

Small Representative Databases for Testing and Validating Density Functionals and Other Electronic Structure Methods.

Broad and diverse sets of accurate data provide useful metrics for assessing the performance of new theoretical methods. However, assessing methods against large databases can be an arduous task. Here, we present 17 representative energetic databases, defined as small databases whose errors and error spreads are representative of larger databases and which therefore can serve as efficient benchmarks for developing and testing electronic structure methods and density functionals. In 15 cases, the representative databases have 6 entries while being representative of larger databases with 14-107 entries, and in the other two cases, they have 14 entries while being representative of larger databases with 418-455 entries. The mean unsigned error (MUE) of 100 electronic structure methods on a given representative database is typically within about 8% of the MUE on its parent database, and the root-mean-square error (RMSE) is typically within about 11% of the RMSE on the parent database. Thus, the representative databases are quite successful in indicating accuracy while maintaining good diversity. The databases include both main-group and transition-metal compounds and reactions, and they include bond energies, reaction energies, barrier heights, noncovalent interactions, ionization potentials, and absolute energies.

Factors associated with reporting left ventricular ejection fraction with 3D echocardiography in real-world practice.

BACKGROUND: Guidelines recommend 3D echocardiography (3DE) to assess left ventricular ejection fraction (LVEF) on transthoracic echocardiogram (TTE) when possible, but it is unclear which factors are most strongly associated with reporting 3DE LVEF in real-world practice. METHODS: We evaluated 3DE LVEF reporting by age, sex, BMI, TTE location and variation in reporting by sonographer and reader. All TTEs were performed without contrast enhancement agent at a large medical center from 9/2015 to 12/2020 using ultrasound machines capable of 3DE. We used multivariable logistic regression to assess which factors were most associated with reporting 3DE LVEF. RESULTS: Among 35 641 TTEs included in this study, 57.4% were performed on women. 3DE LVEF was reported on 18 391 TTEs (51.6% of cohort; 50.5% for women and 52.4% for men). Portable inpatient TTEs (n = 5569) had the lowest rates of 3DE LVEF reporting (30.9%), while general outpatient TTEs (n = 15 933) had greater reporting (56.9%). Outpatient TTEs with an indication for chemotherapy (n = 3244) had the highest rates of 3DE LVEF (87.2%). The median (IQR) percentage of TTEs reporting 3D LVEF was 52.7% (43.1%-68.1%) among sonographers and 51.6% (46.5%-59.6%) among readers. Among 20082 (56.3%) TTEs with 3DE LVEF measured by sonographers, 91.6% were included by readers in the final report. After adjustment, performing sonographer in the highest reporting quartile was most strongly associated with reporting 3DE LVEF (OR 7.04, 95% CI 6.55-7.56), while an inpatient portable study had the strongest negative association for reporting (OR .38, 95% CI .35-.40). CONCLUSIONS: Use of 3DE LVEF in real-world practice varies substantially based on performing sonographer and is low for hospitalized patients, but can be frequently used for chemotherapy. Initiatives are needed to increase sonographer 3DE acquisition in most clinical settings.

Synthesis and antibacterial activity of FST and its effects on inflammatory response and intestinal barrier function in mice infected with Escherichia coli O78.

Pathogenic Escherichia coli (E. coli) can cause intestinal diseases in humans and livestock, damage the intestinal barrier, increase systemic inflammation, and seriously threaten human health and the development of animal husbandry. In this study, we designed and synthesized a novel conjugate florfenicol sulfathiazole (FST) based on drug combination principles, and investigated its antibacterial activity in vitro and its protective effect on inflammatory response and intestinal barrier function in E. coli O78-infected mice in vivo. The results showed that FST had superior antibacterial properties and minimal cytotoxicity compared with its prodrugs as florfenicol and sulfathiazole. FST protected mice from lethal E. coli infection, reduced clinical signs of inflammation, reduced weight loss, alleviated intestinal structural damage. FST decreased the expression of inflammatory cytokines IL-1ß, IL-6, TNF-α, and increased the expression of claudin-1, Occludin, and ZO-1 in the jejunum, improved the intestinal barrier function, and promoted the absorption of nutrients. FST also inhibited the expression of TLR4, MyD88, p-p65, and p-p38 in the jejunum. The study may lay the foundation for the development of FST as new drugs for intestinal inflammation and injury in enteric pathogen infection.