BackgroundConventional prenatal screening tests, such as maternal serum tests and ultrasound scan, have limited resolution and accuracy.MethodsWe developed an advanced noninvasive prenatal diagnosis method based on massively parallel sequencing. The Noninvasive Fetal Trisomy (NIFTY) test, combines an optimized Student’s t-test with a locally weighted polynomial regression and binary hypotheses. We applied the NIFTY test to 903 pregnancies and compared the diagnostic results with those of full karyotyping.Results16 of 16 trisomy 21, 12 of 12 trisomy 18, two of two trisomy 13, three of four 45, X, one of one XYY and two of two XXY abnormalities were correctly identified. But one false positive case of trisomy 18 and one false negative case of 45, X were observed. The test performed with 100% sensitivity and 99.9% specificity for autosomal aneuploidies and 85.7% sensitivity and 99.9% specificity for sex chromosomal aneuploidies. Compared with three previously reported z-score approaches with/without GC-bias removal and with internal control, the NIFTY test was more accurate and robust for the detection of both autosomal and sex chromosomal aneuploidies in fetuses.ConclusionOur study demonstrates a powerful and reliable methodology for noninvasive prenatal diagnosis.

Toward an understanding of the protein interaction network of the human liverAn extensive interaction network of human liver-expressed proteins is described, composed of 3484 interactions among 2582 proteins. Proteins associated with liver disease tend to be central and highly connected in the network.

Context: Maternal thyroid disorders during early pregnancy can influence pregnancy outcome and fetal development. The recent Endocrine Society Clinical Practice Guideline recommends a casefinding approach in which pregnant women who are at high risk for developing thyroid disease are tested. Objective: The purpose of this study was to use the first trimester-specific reference intervals of thyroidrelated hormones to explore the prevalence of thyroid dysfunction during early pregnancy and to analyze effectiveness of different screening strategies. Design: A multicenter cohort study. Method: A total of 2899 pregnant women were enrolled in this study during their first trimester of gestation. Levels of TSH, free thyroxine, free triiodothyronine, and thyroid peroxidase antibodies (TPOAb) were measured and thyroid disorders of pregnant women were diagnosed based on the first trimester-specific reference intervals. Results: The prevalence of hypothyroidism was significantly higher in the high-risk group than in the non-high-risk group (10.9 vs 7.0%, c 2 Z7.1, PZ0.008). The prevalence of hyperthyroidism was not significantly different between the high-risk group and the non-high-risk group (2.7 vs 1.6%, c 2 Z2.27, PZ0.13). Elevated levels of TPOAb and a personal history of thyroid disease increased the risk of thyroid dysfunction. Conclusions: A case-finding strategy for screening thyroid function in the high-risk group would miss about 81.6% pregnant women with hypothyroidism and 80.4% pregnant women with hyperthyroidism.

Success in the differentiating human embryonic stem cells (hESCs) into insulin-secreting β cells raises new hopes for diabetes treatment. In this work, we demonstrated the feasibility of developing islet organoids from hESCs within biomimetic 3D scaffolds. We showed that such a 3D microenvironment is critical to the generation of pancreatic endoderm and endocrine from hESCs. The organoids formed consisted of pancreatic α, β, δ, and pancreatic polypeptide (PP) cells. A high-level co-expression of PDX1, NKX6.1, and NGN3 in these cells suggests the characteristics of pancreatic β cells. More importantly, most insulin-secreting cells generated did not express glucagon, somatostatin, or PP. The expression of mature β cell marker genes such as Pdx1, Ngn3, Insulin, MafA, and Glut2 was detected in these 3D-induced cell clusters. A high-level expression of C-peptide confirmed the de novo endogenous insulin production in these 3D induced cells. Insulin-secretory granules, an indication of β cell maturity, were detected in these cells as well. Glucose challenging experiments suggested that these cells are sensitive to glucose levels due to their elevated maturity. Exposing the cells to a high concentration of glucose induced a sharp increase in insulin secretion.

An association between ID and isolated hypothyroxinemia was found in both pregnant and nonpregnant childbearing-aged women, independent of the effects of iodine and thyroid autoimmunity. We speculate that ID may be a pathogenic factor for hypothyroxinemia, even in pregnant women during the first trimester.