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The uptick in SARS-CoV-2 infection has resulted in a worldwide COVID-19 pandemic, which has created troublesome health and economic problems. We performed case–control meta-analyses in both African and European ethnicity COVID-19 disease cases based on laboratory test and phenotypic criteria. The cases had laboratory-confirmed SARS-CoV-2 infection. We uniquely investigated COVID infection genetics in a pediatric population. Our cohort has a large African ancestry component, also unique to our study. We tested for genetic variant association in 498 cases vs. 1,533 controls of African ancestry and 271 cases vs. 855 controls of European ancestry. We acknowledge that the sample size is relatively small, owing to the low prevalence of COVID infection among pediatric individuals. COVID-19 cases averaged 13 years of age. Pediatric genetic studies enhance the ability to detect genetic associations with a limited possible environment impact. Our findings support the notion that some genetic variants, most notably at the SEMA6D, FMN1, ACTN1, PDS5B, NFIA, ADGRL3, MMP27, TENM3, SPRY4, MNS1, and RSU1 loci, play a role in COVID-19 infection susceptibility. The pediatric cohort also shows nominal replication of previously reported adult study results: CCR9, CXCR6, FYCO1, LZTFL1, TDGF1, CCR1, CCR2, CCR3, CCR5, MAPT-AS1, and IFNAR2 gene variants. Reviewing the biological roles of genes implicated here, NFIA looks to be the most interesting as it binds to a palindromic sequence observed in both viral and cellular promoters and in the adenovirus type 2 origin of replication.

Herein, three novel cocrystals of 1-hydroxy-2-naphthoic acid: tetramethylpyrazine, 1-hydroxy-2-naphthoic acid:1,10-phenanthroline, and 1-hydroxy-2-naphthoic acid:1,4-bis(imidazol-1-ylmethyl)benzene (L2) were obtained by crystallization in methanol–water mixed solvent via a slow evaporation method. The cocrystalline products 1−3 were carried out by a range of techniques, including single-crystal X-ray diffraction, Fourier transform–infrared spectroscopy, elemental analysis, and thermogravimetric testing. We analyzed the crystal structures of the cocrystals 1−3 and found that weak interactions C–H···X (X = O or π) were of great importance in the process of self-assembly as well as strong and conventional hydrogen bonds (N–H···O, O–H···N, O–H···O), leading to a stable and diverse multidimensional supramolecular architecture. It is worth noting that a series of ring motifs with different sizes were explored in the crystal structures of the above complexes, such as R22(5), R22(7), R22(8), R23(13), R24(16), R44(16), R44(22), and so on. The classical and robust supramolecular synthon intermolecular bond between acid and pyridine (acid···pyridine) heterosynthon R22(7), commonly found in organic solids containing carboxylic acids with other N-containing heteroaromatics, was further demonstrated to be involved in the construction of the hydrogen-bond networks of cocrystal 1. The thermogravimetric technique used in this study proved that the mass losses of these three cocrystals were closely related to the strength of the hydrogen bonds in the package fraction.

Congenital heart defects (CHDs) are a common birth defect, affecting approximately 1% of newborn children in the United States. As previously reported, a significant number of CHDs are potentially attributed to altered copy number variants (CNVs). However, as many genomic variants are rare, a large-scale CNV triad study is necessary to characterize the genetic architecture of CHD. We used whole-exome sequencing (WES) data generated by the Pediatric Cardiac Genomics Consortium (PCGC), including a discovery dataset of 2,103 individuals from 760 nuclear family trios and an independent replication set of 4,808 individuals from 1,712 trios. The candidate targets uncovered were further validated through different platforms, including the Omni single-nucleotide polymorphism (SNP) array chip in 1,860 individuals and the whole-genome sequencing (WGS) data in 33 trios. The genes harboring CNVs of interest were then investigated for expression alternations based on cardiac tissue RNA-Seq data. We identified multiple CNVs in the WES data that associated with specific sub-phenotypes of CHD in approximately 2,400 families, including 98 de novo CNV regions. We identified five CNV loci harboring LIMS1, GCC2, RANBP2, TTC3, and MAP3K7CL, respectively, where those genes are highly expressed in human heart and/or mouse embryo heart at 15 days. Five novel CNV loci were uncovered, demonstrating altered expression of the respective candidate genes involved. To our knowledge, this is the largest trio-based WES study of CHD and, in addition to uncovering novel CHD targets, presents an extensive resource with the potential to provide important insights to the architecture and impact of CNVs in CHD.

Juvenile idiopathic arthritis (JIA) is highly heterogeneous in terms of etiology and clinical presentation with ambiguity in JIA classification. The advance of high-throughput omics technologies in recent years has gained us significant knowledge about the molecular mechanisms of JIA. Besides a minor proportion of JIA cases as monogenic, most JIA cases are polygenic disease caused by autoimmune mechanisms. A number of HLA alleles (including both HLA class I and class II genes), and 23 non-HLA genetic loci have been identified of association with different JIA subtypes. Omics technologies, i.e., transcriptome profiling and epigenomic analysis, contributed significant knowledge on the molecular mechanisms of JIA in addition to the genetic approach. New molecular knowledge on different JIA subtypes enables us to reconsider the JIA classification, but also highlights novel therapeutic targets to develop a cure for the devastating JIA.

Objective To investigate the effects of Cushing’s disease (CD) and adrenal-dependent Cushing’s syndrome (ACS) on bone mineral density (BMD) and bone metabolism. Methods Data were retrospectively collected for 55 patients with hypercortisolism (CD, n = 34; ACS n = 21) from January 1997 to June 2014. BMD was examined in all patients, and bone turnover markers were tested in some patients. Healthy controls (n = 18) were also recruited. Results The lumbar spine and femoral neck BMD were significantly lower in the ACS and CD groups than in the control group. Lumbar BMD was significantly lower in the ACS than CD group. The collagen breakdown product (CTX) concentrations were significantly higher while the osteocalcin and procollagen type I N-terminal propeptide (PINP) concentrations were significantly lower in the ACS and CD groups than in the control group. The PINP concentration was significantly lower while the CTX concentration was significantly higher in the ACS than CD group. In the CD group only, lumbar BMD and serum adrenocorticotropic hormone had a significant positive correlation. Conclusions Bone turnover markers indicated suppressed osteoblast and enhanced osteoclast activities. PINP and CTX changes might indicate bone mass deterioration. Adrenocorticotropic hormone might be protective for lumbar BMD in patients with CD.

The uptick in SARS-CoV-2 infection has resulted in a worldwide COVID-19 pandemic, which has created troublesome health and economic problems. We performed case-control meta-analyses in both African and European ethnicity COVID-19 disease cases based on laboratory test and phenotypic criteria. The cases had laboratory-confirmed SARS-CoV-2 infection. We uniquely investigated COVID infection genetics in a pediatric population. Our cohort has a large African ancestry component, also unique to our study. We tested for genetic variant association in 498 cases vs. 1,533 controls of African ancestry and 271 cases vs. 855 controls of European ancestry. We acknowledge that the sample size is relatively small, owing to the low prevalence of COVID infection among pediatric individuals. COVID-19 cases averaged 13 years of age. Pediatric genetic studies enhance the ability to detect genetic associations with a limited possible environment impact. Our findings support the notion that some genetic variants, most notably at the SEMA6D, FMN1, ACTN1, PDS5B, NFIA, ADGRL3, MMP27, TENM3, SPRY4, MNS1, and RSU1 loci, play a role in COVID-19 infection susceptibility. The pediatric cohort also shows nominal replication of previously reported adult study results: CCR9, CXCR6, FYCO1, LZTFL1, TDGF1, CCR1, CCR2, CCR3, CCR5, MAPT-AS1, and IFNAR2 gene variants. Reviewing the biological roles of genes implicated here, NFIA looks to be the most interesting as it binds to a palindromic sequence observed in both viral and cellular promoters and in the adenovirus type 2 origin of replication. [ABSTRACT FROM AUTHOR]