Objectives To explore the contribution of single‐gene defects to the genetic cause of cardiac left‐sided lesions (LSLs), and to evaluate the incremental diagnostic yield of whole‐exome sequencing (WES) for single‐gene defects in fetuses with LSLs without aneuploidy or a pathogenic copy‐number variant (pCNV). Methods Between 10 April 2015 and 30 October 2018, we recruited 80 pregnant women diagnosed with a LSL who had termination of pregnancy and genetic testing. Eligible LSLs were aortic valve atresia or stenosis, coarctation of the aorta, mitral atresia or stenosis and hypoplastic left heart syndrome (HLHS). CNV sequencing (CNV‐seq) and WES were performed sequentially on specimens from these fetuses and their parents. CNV‐seq was used to identify aneuploidies and pCNVs, while WES was used to identify diagnostic genetic variants in cases without aneuploidy or pCNV. Results Of 80 pregnancies included in the study, 27 (33.8%) had a genetic diagnosis. CNV‐seq analysis identified six (7.5%) fetuses with aneuploidy and eight (10.0%) with pCNVs. WES analysis of the remaining 66 cases revealed diagnostic genetic variants in 13 (19.7%) cases, indicating that the diagnostic yield of WES for the entire cohort was 16.3% (13/80). KMT2D was the most frequently mutated gene (7/66 (10.6%)) in fetuses with LSL without aneuploidy or pCNVs, followed by NOTCH1 (4/66 (6.1%)). HLHS was the most prevalent cardiac phenotype (4/7) in cases with a KMT2D mutation in this cohort. An additional six (9.1%) cases were found to have potentially deleterious variants in candidate genes. Conclusions Single‐gene defects contribute substantially to the genetic etiology of fetal LSLs. KMT2D mutations accounted for approximately 10% of LSLs in our fetal cohort. WES has the potential to provide genetic diagnoses in fetuses with LSLs without aneuploidy or pCNVs. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Abstract:Over three million hectares of salt-affected soils characterized with high salinity and sodicity caused serious land degradation in Songnen Plain, northeast China. Soil salinity-sodicity heterogeneous distribution under microtopography is usually influenced by several environmental factors. The side direction movement of soil water driven by water from depression is the key factor that aggravates the soil salinization under microtopography in dry condition. In this study, the differences in surface soil salinity-sodicity (0-10 cm) between dry year and wet year were compared, and the relationship between soil salinity-sodicity and environment factors such as ground elevation, surface ponding time, surface ponding depth, and soil moisture at four soil layers (0-10, 10-30, 30-60, and 60-100 cm) were analyzed using redundancy analysis (RDA) and simple correlation analysis (Pearson analysis) for two different hydrological years. Analyzed soil salinity-sodicity parameters include soluble ions (Na + , K + , Ca 2+ , Mg 2+ , CO 3 2´, HCO 3´, Cl´and SO 4 2´) , salt content (SC), electrical conductivity (EC), sodium adsorption ratio (SAR), and pH. Results showed that values of SAR, Cl´, and SO 4 2´w ere significantly higher in dry year than in wet year, while Ca 2+ , Mg 2+ , K + , and HCO 3´s howed the opposite results. Values of Na + , CO 3 2´, and EC were significantly higher at higher ground elevation gradient (20-40 cm) in dry year than wet year. Redundancy analysis indicated that spatial distributions and variations of salinity and sodicity in surface soil layer were related with environmental factors of ponding depth, ponding time and ground elevation in wet year, and they were related with ground elevation, ponding depth, ponding time, and soil moisture at 30-60 and 60-100 cm soil layer in dry year. Ponding depth and ground elevation rank first and second as the influential factors of the spatial distribution and variation of soil salinity-sodicity in wet year. However in dry year, primary and secondary influential factors are ground elevation and soil moisture at 60-100 cm soil layer.

AIMTo investigate the efficacy of switching to pegylated interferon-α-2a (PegIFNα-2a) treatment in nucleos(t)ide analog (NA)-treated chronic hepatitis B (CHB) responder patients.METHODSA 48-wk prospective and retrospective treatment trial of NA-treated CHB patients who had received entecavir (ETV) for at least 48 wk and had serum hepatitis B virus (HBV)-DNA < 500 IU/mL, serum hepatitis B envelope antigen (HBeAg) < 100 S/CO, serum alanine aminotransferase, and aspartate aminotransferase levels < 2 × the upper limit of normal of 40 IU/L was performed. The effects on virological and serological responses and adverse reactions to 0.5 mg daily ETV for 48 wk vs switching to PegIFNα-2a were compared. Forty-four patients were randomized to be switched from NA treatment to the PegIFNα-2a group, and 44 patients were simultaneously randomized to the ETV group.RESULTSAfter 48 wk of therapy, the decrease in hepatitis B surface antigen (HBsAg) levels was greater in the PegIFNα-2a group than in the ETV group (3.1340 log10 IU/mL vs 3.6950 log10 IU/mL, P = 0.00). Seven patients who were anti-HBs-positive at baseline achieved HBsAg loss when switched to PegIFNα-2a (15.91% vs 0%, P = 0.018). The HBeAg serological conversion rate was higher in the PegIFNα-2a group than in the ETV group; however, the difference was not significant because of the small sample sizes (34.38% vs 21.88%, P = 0.232). In the PegIFNα-2a group, patients with HBsAg levels < 1500 IU/mL at baseline had higher HBeAg seroconversion and HBsAg loss rates at week 48 than those with HBsAg levels ≥ 1500 IU/mL (HBeAg seroconversion: 17.86% vs 62.5%, P = 0.007; HBsAg loss: 41.67% vs 6.25%, P = 0.016). Moreover, patients with HBsAg levels < 1500 IU/mL at week 24 had higher HBsAg loss rates after therapy than those with HBsAg levels ≥ 1500 IU/mL (36.84% vs 0%, P = 0.004). However, there were no statistically significant differences in HBeAg seroconversion rates (47.06% vs 25.93%, P = 0.266).CONCLUSIONNA-treated CHB patients switched to sequential PegIFNα-2a achieved highly potent treatment termination safely.

Core Ideas Net returns were higher for conventional tillage than no‐tillage without cover crops. Net returns were higher for no‐tillage than conventional tillage with cover crops. A cotton producer would maximize profits by not planting cover crops. The objective of this study was to evaluate the long‐term effects of winter cover crops with and without tillage on profit‐maximizing N fertilization rate and net return for upland cotton (Gossypium hirsutum L.) production. Data came from a 29‐yr (1984–2012) cotton experiment located in Jackson, TN. The experiment included four cover crop treatments (no cover, winter wheat [Triticum aestivum L.], hairy vetch [Vicia villosa L.], and crimson clover [Trifolium incarnatum L.]); two tillage systems (no‐tillage [NT] and conventional tillage [CT]), and four N fertilizer rates (0, 34, 67, or 101 kg N ha−1). Lint yield was de‐trended for temporal yield variation and quadratic yield response functions to N fertilizer were estimated for each cover crop and tillage system. Partial budgeting was used to determine the profit‐maximizing N rate and yields for each cover crop and tillage combinations under different cotton and N price scenarios. The highest profit‐maximizing N fertilizer rate savings, relative to no cover, under CT and NT were for cotton after clover, followed by cotton after hairy vetch and then cotton after wheat. Maximum net returns for cotton after hairy vetch, cotton after crimson clover, and cotton after wheat were lower than for cotton with no cover under CT and NT systems. The results show that revenue gains from producing cotton following cover crops did not offset the cost of cover establishment compared to cotton following no cover. A cotton producer would maximize profits by not planting cover crops under various price scenarios.