Identification of susceptibility genes in non-syndromic cleft lip with or without cleft palate using whole-exome sequencing

Background: Non-syndromic cleft lip with or without cleft palate (NSCL/P) is among the most common congenital malformations. The etiology of NSCL/P remains poorly characterized owing to its complex genetic heterogeneity. The objective of this study was to identify genetic variants that increase susceptibility to NSCL/P. Material and Methods: Whole-exome sequencing (WES) was performed in 8 fetuses with NSCL/P in China. Bioinformatics analysis was performed using commercially available software. Variants detected by WES were validated by Sanger sequencing. Results: By filtering out synonymous variants in exons, we identified average 8575 nonsynonymous single nucleotide variants (SNVs). We subsequently compared the SNVs against public databases including NCBI dbSNP build 135 and 1000 Genomes Project and obtained an average of 203 SNVs. Total 12 reported candidate genes were verified by Sanger sequencing. Sanger sequencing also confirmed 16 novel SNVs shared by two or more samples. Conclusions: We have found and confirmed 16 susceptibility genes responsible for NSCL/P, which may play important role in the etiology of NSCL/P. The susceptibility genes identified in this study will not only be useful in revealing the etiology of NSCL/P but also in diagnosis and treatment of the patients with NSCL/P

Association of hematological parameters with metabolic syndrome in Beijing adult population: a longitudinal study

The purposes of the study were to estimate the incidence of metabolic syndrome (MetS) and to systematically evaluate the relationship between hematological parameters and MetS in a 5-year follow-up of Beijing adult population. The longitudinal study included 3,180 adults, aged 20–65 years, who attended health check-ups in Beijing Tongren Hospital in 2007 and 2012. Multivariate logistic regression was conducted to explore the associations between hematological parameters and MetS. The 5-year cumulative incidence of MetS in this sample was 10.82 % (14.22 % for males and 7.59 % for females). Among all the hematological parameters, white blood cell count (WBC) was positively associated with MetS for 20–35-year-old (male OR 1.482, 95 % CI 1.169–2.974; female OR 1.398, 95 % CI 1.145–3.011), and 36–50-year-old (male OR 2.012, 95 % CI 1.290–4.010; female OR 3.400, 95 % CI 1.818–4.528) male and female subjects. Alanine aminotransferase (ALT) was significantly associated with the incidence of MetS for males (20–35-year-old OR 2.080, 95 % CI 1.371–3.159; 36–50-year-old OR 2.421, 95 % CI 1.335–3.412; 51–65-year-old OR 4.267, 95 % CI 1.161–6.781). Low-density lipoprotein cholesterol (LDL-C) was positively associated with MetS for 51–65-year-old (male OR 3.078, 95 % CI 2.468–5.131; female OR 2.140, 95 %CI 1.524–4.359) for male and female subjects. WBC is positively associated with MetS for young adults, while LDL-C is positively associated with MetS for elderly people. ALT is positively associated with MetS for males. Our findings provide further evidence in support of using hematological markers for early detection of individuals at risk for MetS

Analisa Kepuasan Konsumen Di Restaurant “X” Di Surabaya

Penelitian ini ditunjukan untuk menganalisa tingkat kesenjangan antara harapan dari konsumen terhadap Kenyataan yang diterima oleh konsumen dan mengukur tingkat kepuasan konsumen di Restoran “X” dengan menggunakan atribut DINESERV. Penelitian ini menggunakan Importance Performance Analysis(IPA). Hasil dari penelitian ini adalah kesenjangan antara harapan dan Kenyataan yang diukur menggunakan atribut DINESERV adalah Kenyataan yang diterima oleh konsumen sangat tidak sesuai dengan harapan konsumen dan konsumen sangat tidak puas terutama dengan atribut Convenience Restoran yaitu Jarak dari Restoran “X” di Surabay

Correlations between the optic nerve head morphology and ocular biometrics in highly myopic eyes

AIM: To analyze peripapillary atrophy β/γ zone (PPA-β/γ) and the optic disc ovality index, and to assess their associations with the axial length (AL), refractive error, best corrected visual acuity (BCVA), choroidal thickness (CT), and age in highly myopic eyes. METHODS: This was a retrospective observational case series. The study included 667 patients consecutively examined for highly myopic eyes [spherical equivalent ≤-6.0 diopters (D) and AL≥26 mm] with or without myopic retinopathy. Each patient went through a comprehensive ophthalmological examination that included spectral domain optical coherence tomography (SD-OCT) of the macula, A-mode ultrasonography, and a cycloplegic refraction test. The ovality index and PPA-β/γ area were measured from optic disc photographs. RESULTS: A significant association was seen between PPA-β/γ area and the ovality index (P=0.000, r=-0.232). The PPA-β/γ area increased significantly with a longer AL, older age, worse BCVA, higher refractive error, and thinner choroid (P<0.01). The oval disc was significantly correlated with a longer AL, older age, worse BCVA, higher refractive error, larger PPA-β/γ area, and thinner choroid (P<0.01). CONCLUSION: The PPA-β/γ zone and ovality index in highly myopic eyes show distinct associations with the AL, refractive error, BCVA, age, and CT

Notolutesins A–J, Dolabrane-Type Diterpenoids from the Chinese Liverwort Notoscyphus lutescens

Ten new dolabrane-type diterpenoids, notolutesins A–J (1–10), were isolated from the Chinese liverwort Notoscyphus lutescens, along with four known compounds. The structures of the new compounds were established on the basis of extensive spectroscopic data, and that of 1 was confirmed by single-crystal X-ray crystallography. The absolute configuration of 1 was determined by comparing its experimental and calculated electronic circular dichroism spectra. All of the isolates were evaluated for their cytotoxicity against a small panel of human cancer cell lines, and compound 1 exhibited an IC50 value of 6.2 μM against the PC3 human prostate cancer cell line

Upregulation of Circulating PD-L1/PD-1 Is Associated with Poor Post-Cryoablation Prognosis in Patients with HBV-Related Hepatocellular Carcinoma

BACKGROUND: The programmed cell death-1 receptor/programmed cell death-1 ligand (PD-1/PD-L1) pathway plays a crucial role in tumor evasion from host immunity. This study was designed to evaluate the association between circulating PD-L1/PD-1 and prognosis after cryoablation in patients with HBV-related hepatocellular carcinoma (HCC). METHODOLOGY/PRINCIPAL FINDINGS: In the present study, 141 HBV-related HCC patients were enrolled and of those 109 patients received cryoablation. Circulating PD-L1/PD-1 expression was tested by flow cytometry, and 23 patients were simultaneously evaluated for intratumoral PD-L1 expression by immunohistochemical staining. Circulating PD-1/PD-L1 expression was associated with severity of diseases in patients with HCC, and the circulating PD-L1 expression was closely correlated with intratumoral PD-L1 expression. Of the clinical parameters, PD-1/PD-L1 expression was associated with tumor size, blood vessel invasion and BCLC staging. Moreover, PD-1/PD-L1 expression dropped after cryoablation while being elevated at the time of tumor recurrence. Patients with higher expression of circulating PD-L1, as well as circulating PD-1, had a significantly shorter overall survival and tumor-free survival than those with lower expression. Multivariate analysis confirmed that circulating PD-L1 could serve as an independent predictor of overall survival and tumor-recurrence survival in HCC patients after cryoablation. CONCLUSIONS/SIGNIFICANCE: Upregulation of circulating PD-L1/PD-1 is associated with poor post-cryoablation prognosis in patients with HBV-related hepatocellular carcinoma

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks