Author Correction: Early pregnancy ultrasound measurements and prediction of first trimester pregnancy loss: A logistic model (Scientific Reports, (2020), 10, 1, (1545), 10.1038/s41598-020-58114-3)

The original version of this Article contained an error in the spelling of the author Patricia J. Goedecke which was incorrectly given as Patricia J. Goeske. The original Article has been corrected

Genetically Determined Plasma Lipid Levels and Risk of Diabetic Retinopathy: A Mendelian Randomization Study.

Results from observational studies examining dyslipidemia as a risk factor for diabetic retinopathy (DR) have been inconsistent. We evaluated the causal relationship between plasma lipids and DR using a Mendelian randomization approach. We pooled genome-wide association studies summary statistics from 18 studies for two DR phenotypes: any DR (N = 2,969 case and 4,096 control subjects) and severe DR (N = 1,277 case and 3,980 control subjects). Previously identified lipid-associated single nucleotide polymorphisms served as instrumental variables. Meta-analysis to combine the Mendelian randomization estimates from different cohorts was conducted. There was no statistically significant change in odds ratios of having any DR or severe DR for any of the lipid fractions in the primary analysis that used single nucleotide polymorphisms that did not have a pleiotropic effect on another lipid fraction. Similarly, there was no significant association in the Caucasian and Chinese subgroup analyses. This study did not show evidence of a causal role of the four lipid fractions on DR. However, the study had limited power to detect odds ratios less than 1.23 per SD in genetically induced increase in plasma lipid levels, thus we cannot exclude that causal relationships with more modest effect sizes exist

Three-Dimensional Imaging of Drosophila melanogaster

The major hindrance to imaging the intact adult Drosophila is that the dark exoskeleton makes it impossible to image through the cuticle. We have overcome this obstacle and describe a method whereby the internal organs of adult Drosophila can be imaged in 3D by bleaching and clearing the adult and then imaging using a technique called optical projection tomography (OPT). The data is displayed as 2D optical sections and also in 3D to provide detail on the shape and structure of the adult anatomy.We have used OPT to visualize in 2D and 3D the detailed internal anatomy of the intact adult Drosophila. In addition this clearing method used for OPT was tested for imaging with confocal microscopy. Using OPT we have visualized the size and shape of neurodegenerative vacuoles from within the head capsule of flies that suffer from age-related neurodegeneration due to a lack of ADAR mediated RNA-editing. In addition we have visualized tau-lacZ expression in 2D and 3D. This shows that the wholemount adult can be stained without any manipulation and that this stain penetrates well as we have mapped the localization pattern with respect to the internal anatomy.We show for the first time that the intact adult Drosophila can be imaged in 3D using OPT, also we show that this method of clearing is also suitable for confocal microscopy to image the brain from within the intact head. The major advantage of this is that organs can be represented in 3D in their natural surroundings. Furthermore optical sections are generated in each of the three planes and are not prone to the technical limitations that are associated with manual sectioning. OPT can be used to dissect mutant phenotypes and to globally map gene expression in both 2D and 3D

Measuring What Works: An Impact Evaluation of Women's Groups on Maternal Health Uptake in Rural Nepal.

BACKGROUND: There is a need for studies evaluating maternal health interventions in low-income countries. This paper evaluates one such intervention designed to promote maternal health among rural women in Nepal. METHODS AND RESULTS: This was a five-year controlled, non-randomised, repeated cross-sectional study (2007, 2010, 2012) of a participatory community-based maternal health promotion intervention focusing on women's groups to improve maternal health services uptake. In total 1,236 women of childbearing age, who had their last child ≤ two years ago, were interviewed. Difference-in-Difference estimation assessed the effects of the intervention on selected outcome variables while controlling for a constructed wealth index and women's characteristics. In the first three years (from 2007 to the 2010), the intervention increased women's likelihood of attending for antenatal care at least once during pregnancy by seven times [OR = 7.0, 95%CI (2.3; 21.4)], of taking iron and folic acid by three times [OR = 3.0, 95%CI (1.2; 7.8)], and of seeking four or more antenatal care visits of two times, although not significantly [OR = 2.2, 95%CI (1.0; 4.7)]. Over five years, women were more likely to seek antenatal care at least once [OR = 3.0, 95%CI (1.5; 5.2)], to take iron/folic acid [OR = 1.9, [95% CI (1.1; 3.2)], and to attend postnatal care [OR = 1.5, [95% CI (1.1; 2.2)]. No improvement was found on attending antenatal care in the first trimester, birthing at an institution or with a skilled birth attendant. CONCLUSION: Community-based health promotion has a much stronger effect on the uptake of antenatal care and less on delivery care. Other factors not easily resolved through health promotion interventions may influence these outcomes, such as costs or geographical constraints. The evaluation has implications for policy and practice in public health, especially maternal health promotion

Human and mouse essentiality screens as a resource for disease gene discovery.

The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines. We propose a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing biological properties. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented among genes non-essential for cell survival but required for organism development. After screening developmental disorder cases from three independent disease sequencing consortia, we identify potentially pathogenic variants in genes not previously associated with rare diseases. We therefore propose FUSIL as an efficient approach for disease gene discovery

Teaching and Generative AI

With the rapid development of generative AI, teachers are experiencing a new pedagogical challenge, one that promises to forever change the way we approach teaching and learning. As a response to this unprecedented teaching context, this collection—Teaching and Generative AI: Pedagogical Possibilities and Productive Tensions—provides interdisciplinary teachers, librarians, and instructional designers with practical and thoughtful pedagogical resources for navigating the possibilities and challenges of teaching in an AI era. Because our goal with this edited collection is to present nuanced discussions of AI technologies across disciplines, the chapters collectively acknowledge or explore both possibilities and tensions—including the strengths, limitations, ethical considerations, and disciplinary potential and challenges—of teaching in an AI era. As such, the authors in this collection do not simply praise or criticize AI, but thoughtfully acknowledge and explore its complexities within educational settings

FTO genetic variants, dietary intake and body mass index: insights from 177 330 individuals

FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177 330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m2, P = 1.9 × 10−105), and all participants (0.30 [0.30, 0.35] kg/m2, P = 3.6 × 10−107). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10−16), and relative weak associations with lower total energy intake (−6.4 [−10.1, −2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (−0.07 [−0.11, −0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10−9) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposit

Human and mouse essentiality screens as a resource for disease gene discovery

The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines. We propose a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing biological properties. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented among genes non-essential for cell survival but required for organism development. After screening developmental disorder cases from three independent disease sequencing consortia, we identify potentially pathogenic variants in genes not previously associated with rare diseases. We therefore propose FUSIL as an efficient approach for disease gene discovery. Discovery of causal variants for monogenic disorders has been facilitated by whole exome and genome sequencing, but does not provide a diagnosis for all patients. Here, the authors propose a Full Spectrum of Intolerance to Loss-of-Function (FUSIL) categorization that integrates gene essentiality information to aid disease gene discovery