bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a Core Outcome Set for Studies on Cardiac Disease in Pregnancy (COSCarP): a study protocol
Authors: D’Souza Rohan , Hall Chelsea , Sermer Mathew , Siu Samuel , Silversides Candice 
Published: March 2020

Abstract
Background
Clinical studies looking at interventions to optimize pregnancy and long-term outcomes for women with cardiac disease and their babies are inconsistent in their reporting of clinical outcomes, making it difficult to compare results across studies and draw meaningful conclusions. The development of a core outcome set (COS)—a standardized, minimum set of outcomes that must be collected and reported in all studies—is a practical solution to this problem.

Methods/design
We will follow a five-step process in developing a COS for studies on pregnant women with cardiac disease. First, a systematic literature review will identify all reported outcomes (including patient-reported outcomes) and definitions. Second, semi-structured interviews with stakeholders involved in the care of pregnant women with cardiac disease will determine their perspective and add new outcomes that they consider important. Third, an international electronic Delphi survey will narrow outcomes obtained through the first two steps, in an attempt to arrive at a consensus. Fourth, a face-to-face consensus meeting will deliberate to finalize the COS. Finally, measurement tools and definitions for included outcomes will be determined through a series of literature reviews and Delphi surveys.

Discussion
This protocol provides an overview of the steps involved in the development of a COS that must be reported in studies involving pregnant women with cardiac disease, in an attempt to harmonize outcome reporting and ensure the validity of study results that will not only inform clinical practice and future research but also encourage the development of COS in other areas of medicine.

COMET core outcome set registration
http://www.cometinitiative.org/studies/details/834
Synthesis, bioactivities and phloem uptake of dipeptide-chlorantraniliprole derivatives
Authors: Zheng Shijie , Lin Xiaomin , Wu Hanxiang , Zhao Chen , Xu Hanhong 
Published: March 2020

AbstractPhloem systemicity is a desirable property for insecticides to control sucking insects. However, the development of phloem systemic insecticides is challenging. One possible strategy is to link existed insecticides with endogenous substances so that the resulting conjugates can be transported by specific transporters into the phloem. In this study, novel dipeptide promoieties were introduced into chlorantraniliprole, which is an efficient and broad-spectrum anthranilic diamide insecticide without phloem mobility. Twenty-two new dipeptide-chlorantraniliprole conjugates have been synthesized. Systemic tests showed that all conjugates exhibited phloem mobility in Ricinus communis. In particular, compound 4g with alanyl-alanine dipeptide fragment was able to accumulate in phloem sap (114.49 ± 11.10 μM) in the form of its hydrolysis product 5g. Results of bioassay showed that conjugates 4g and 5g were able to exhibit comparable insecticidal activity against Plutella xylostella L. and Spodoptera exigua compared to its parent compound chlorantraniliprole. This work demonstrated that the dipeptide structures were able to contribute to the improvement of the uptake and phloem mobility of chlorantraniliprole, and two phloem mobile conjugates with satisfactory in vivo insecticidal effect was obtained as new candidates for high-efficient insecticides.
Ability of near-infrared spectroscopy and chemometrics to predict the age of mosquitoes reared under different conditions
Authors: Ong Oselyne T. W. , Kho Elise A. , Esperança Pedro M. , Freebairn Chris , Dowell Floyd E. , Devine Gregor J. , Churcher Thomas S. 
Published: March 2020

Abstract
Background
Practical, field-ready age-grading tools for mosquito vectors of disease are urgently needed because of the impact that daily survival has on vectorial capacity. Previous studies have shown that near-infrared spectroscopy (NIRS), in combination with chemometrics and predictive modeling, can forecast the age of laboratory-reared mosquitoes with moderate to high accuracy. It remains unclear whether the technique has utility for identifying shifts in the age structure of wild-caught mosquitoes. Here we investigate whether models derived from the laboratory strain of mosquitoes can be used to predict the age of mosquitoes grown from pupae collected in the field.

Methods
NIRS data from adult female Aedes albopictus mosquitoes reared in the laboratory (2, 5, 8, 12 and 15 days-old) were analysed against spectra from mosquitoes emerging from wild-caught pupae (1, 7 and 14 days-old). Different partial least squares (PLS) regression methods trained on spectra from laboratory mosquitoes were evaluated on their ability to predict the age of mosquitoes from more natural environments.

Results
Models trained on spectra from laboratory-reared material were able to predict the age of other laboratory-reared mosquitoes with moderate accuracy and successfully differentiated all day 2 and 15 mosquitoes. Models derived with laboratory mosquitoes could not differentiate between field-derived age groups, with age predictions relatively indistinguishable for day 1–14. Pre-processing of spectral data and improving the PLS regression framework to avoid overfitting can increase accuracy, but predictions of mosquitoes reared in different environments remained poor. Principal components analysis confirms substantial spectral variations between laboratory and field-derived mosquitoes despite both originating from the same island population.

Conclusions
Models trained on laboratory mosquitoes were able to predict ages of laboratory mosquitoes with good sensitivity and specificity though they were unable to predict age of field-derived mosquitoes. This study suggests that laboratory-reared mosquitoes do not capture enough environmental variation to accurately predict the age of the same species reared under different conditions. Further research is needed to explore alternative pre-processing methods and machine learning techniques, and to understand factors that affect absorbance in mosquitoes before field application using NIRS.
A comprehensive overview of bull sperm-borne small non-coding RNAs and their diversity across breeds
Authors: Sellem Eli , Marthey Sylvain , Rau Andrea , Jouneau Luc , Bonnet Aurelie , Perrier Jean-Philippe , Fritz Sébastien , Le Danvic Chrystelle , Boussaha Mekki , Kiefer Hélène , Jammes Hélène , Schibler Laurent 
Published: March 2020

AbstractBackgroundMature sperm carry thousands of RNAs, including mRNAs, lncRNAs, tRNAs, rRNAs and sncRNAs, though their functional significance is still a matter of debate. Growing evidence suggests that sperm RNAs, especially sncRNAs, are selectively retained during spermiogenesis or specifically transferred during epididymis maturation, and are thus delivered to the oocyte at fertilization, providing resources for embryo development. However , a deep characterization of the sncRNA content of bull sperm and its expression profile across breeds is currently lacking. To fill this gap, we optimized a guanidinium–Trizol total RNA extraction protocol to prepare high-quality RNA from frozen bull sperm collected from 40 representative bulls from six breeds. Deep sequencing was performed (40 M single 50-bp reads per sample) to establish a comprehensive repertoire of cattle sperm sncRNA.ResultsOur study showed that it comprises mostly piRNAs (26%), rRNA fragments (25%), miRNAs (20%) and tRNA fragments (tsRNA, 14%). We identified 5p-halves as the predominant tsRNA subgroup in bull sperm, originating mostly from Gly and Glu isoacceptors. Our study also increased by ~ 50% the sperm repertoire of known miRNAs and identified 2022 predicted miRNAs. About 20% of sperm miRNAs were located within genomic clusters, expanding the list of known polycistronic pri-miRNA clusters and defining several networks of co-expressed miRNAs. Strikingly, our study highlighted the great diversity of isomiRs, resulting mainly from deletions and non-templated additions (A and U) at the 3p end. Substitutions within miRNA sequence accounted for 40% of isomiRs, with G>A, U>C and C>U substitutions being the most frequent variations. In addition, many sncRNAs were found to be differentially expressed across breeds.ConclusionsOur study provides a comprehensive overview of cattle sperm sncRNA, and these findings will pave the way for future work on the role of sncRNAs in embryo development and their relevance as biomarkers of semen fertility.
Burden of tumor mutations, neoepitopes, and other variants are weak predictors of cancer immunotherapy response and overall survival
Authors: Wood Mary A. , Weeder Benjamin R. , David Julianne K. , Nellore Abhinav , Thompson Reid F. 
Published: March 2020

AbstractBackgroundTumor mutational burden (TMB; the quantity of aberrant nucleotide sequences a given tumor may harbor) has been associated with response to immune checkpoint inhibitor therapy and is gaining broad acceptance as a result. However, TMB harbors intrinsic variability across cancer types, and its assessment and interpretation are poorly standardized.MethodsUsing a standardized approach, we quantify the robustness of TMB as a metric and its potential as a predictor of immunotherapy response and survival among a diverse cohort of cancer patients. We also explore the additive predictive potential of RNA-derived variants and neoepitope burden, incorporating several novel metrics of immunogenic potential.ResultsWe find that TMB is a partial predictor of immunotherapy response in melanoma and non-small cell lung cancer, but not renal cell carcinoma. We find that TMB is predictive of overall survival in melanoma patients receiving immunotherapy, but not in an immunotherapy-naive population. We also find that it is an unstable metric with potentially problematic repercussions for clinical cohort classification. We finally note minimal additional predictive benefit to assessing neoepitope burden or its bulk derivatives, including RNA-derived sources of neoepitopes.ConclusionsWe find sufficient cause to suggest that the predictive clinical value of TMB should not be overstated or oversimplified. While it is readily quantified, TMB is at best a limited surrogate biomarker of immunotherapy response. The data do not support isolated use of TMB in renal cell carcinoma.
Quantitative assessment of German Holstein dairy cattle colostrum and impact of thermal treatment on quality of colostrum viscosity and immunoglobulins
Authors: Hassan Abdulwahed Ahmed , Ganz Sebastian , Schneider Florian , Wehrend Axel , Khan Izhar U. H. , Failing Klaus , Bülte Michael , Abdulmawjood Amir 
Published: March 2020

Abstract
Objective
This study aimed to determine the color, fat, viscosity, IgG concentration, %Brix and refractive index of fresh postpartum colostrum of German Holstein dairy cattle and assess the impact of different thermal treatments on the visual and dynamic viscosity, in association to IgG concentration, of colostrum that can be used for pasteurization process.

Results
Of the total 40 fresh postpartum colostrum, the color of colostrum (ranging from white-pale yellow to yellow and dark-yellowish), fat (1.4–8.2 100 g−1), IgG (4–116 mg mL−1), %Brix (8.5–35.4%), refractive index (1.3454–1.3905 nD), visual (ranging from watery to liquid and thick) and dynamic (4.9–219 cp) viscosity, were recorded. Statistical analysis between visual and dynamic viscosity of fresh colostrum showed significant correlation coefficients (rs = 634). Moreover, a significant correlation between viscosity and three IgG concentrations was also observed. Heat-treated colostrum showed dynamic viscosity ranged from 25 to 3066 cP, where dynamic viscosity of colostrum before- and after heat-treatment showed no significant correlation. Treated colostrum at 60 °C/60 min and 63.5 °C/30 min containing IgG concentration ≤ 80 mg mL−1 and ≤ 68 mg mL−1 showed no significant change in the viscosity and can successfully be applied for pasteurization of first postpartum colostrum.
Effects of pharmacist intervention on polypharmacy in patients with type 2 diabetes in Japan
Authors: Horii Takeshi , Atsuda Koichiro 
Published: March 2020

Abstract
Objective
Investigation of polypharmacy in patients with type 2 diabetes revealed that medications administered according to the patient’s symptoms and complaints strongly contributed to polypharmacy. We explored the effects of clinical ward pharmacy service, which evaluated the need for symptomatic treatment, therefore minimizing polypharmacy by reducing inappropriate medications.

Results
The number of drugs (hospitalization vs. discharge: 9 [1–17] vs. 7 [1–16], P < 0.001) and rate of polypharmacy (hospitalization vs. discharge: 75.4% vs. 61.1%, P < 0.001) were significantly lower at discharge. Since hospital admission, the number of drugs increased (n = 6, 11%), remained unchanged (n = 15, 28%), decreased by 1 drug (n = 4, 8%), decreased by 2 drugs (n = 3, 6%), and decreased by more than 2 drugs (n = 25, 47%). Daily drug costs were significantly reduced (hospitalization vs. discharge: $8.3 vs. $6.1, P < 0.001).
A naturally-occurring 22-bp coding deletion in Ugt86Dd reduces nicotine resistance in Drosophila melanogaster
Authors: Macdonald Stuart J. , Highfill Chad A. 
Published: March 2020

Abstract
Objective
Segregating genetic variants contribute to the response to toxic, xenobiotic compounds, and identifying these causative sites can help describe the mechanisms underlying metabolism of toxic compounds. In previous work we implicated the detoxification gene Ugt86Dd in the genetic control of larval nicotine resistance in Drosophila melanogaster. Furthermore, we suggested that a naturally-occurring 22-bp deletion that leads to a stop codon in exon 2 of the gene markedly reduces resistance. Here we use homology directed CRISPR/Cas9 gene editing to specifically test this hypothesis.

Results
We edited chromosome three from an inbred strain named A4 which carries the insertion allele at Ugt86Dd, successfully generated four alleles carrying the 22-bp Ugt86Dd deletion, and substituted edited chromosomes back into the A4 background. The original A4 strain, and an un-edited control strain in the same A4 background, show no significant difference in egg-to-adult or larva-to-adult viability on either control media or nicotine-supplemented media, and only slightly delayed development in nicotine media. However, strains carrying the 22-bp deletion showed reduced viability in nicotine conditions, and significantly longer development. Our data strongly suggest that the naturally-occurring 22-bp insertion/deletion event in Ugt86Dd directly impacts variation in nicotine resistance in D. melanogaster.
The study of factors associated with pregnancy outcomes in patients with systemic lupus erythematosus
Authors: Zamani Batool , Shayestehpour Mohammad , Esfahanian Farifteh , Akbari Hossein 
Published: March 2020

Abstract
Objectives
Systemic lupus erythematosus (SLE) is an autoimmune disease that can lead to unfavorable pregnancy complications in women. This study aimed to evaluate the factors associated with pregnancy outcomes in patients with SLE.

Results
Fifty-nine pregnant women with SLE (121 pregnancies) participated in this retrospective cohort study. The mean age of the patients was 33.74 ± 3.80 years (range 21 to 48 years). Fetal loss occurred in 43.8% of pregnancies. The most common laboratory findings in SLE patients were antinuclear antibody (81.4%) and anti-ds DNA positivity (54.2%). High levels of C-reactive protein (CRP) during pregnancy, renal involvement, anti-double-stranded DNA positivity, anti-phospholipid antibody (APA) positivity and younger age at disease onset were significantly correlated with unfavourable pregnancy outcomes. A significant difference was observed between duration of SLE and low birth weight (P = 0.003), pre-eclampsia (P = 0.012) and still birth (P = 0.036). High CRP, APA positivity, anti-dsDNA positivity and kidney involvement were predictors of adverse pregnancy outcomes in SLE patients. Renal involvement increased risk of pregnancy with complication 8.5 times (OR = 8.5, 95% CI 1.396–63.373, P = 0.017). Antiphospholipid syndrome (APS) also was associated with an odds ratio of 5.18 (95% CI 1.681–13.647, P = 0.001).
The association of DNA methylation with body mass index: distinguishing between predictors and biomarkers
Authors: Reed Zoe E. , Suderman Matthew J. , Relton Caroline L. , Davis Oliver S. P. , Hemani Gibran 
Published: March 2020

Abstract
Background
DNA methylation is associated with body mass index (BMI), but it is not clear if methylation scores are biomarkers for extant BMI or predictive of future BMI. Here, we explore the causal nature and predictive utility of DNA methylation measured in peripheral blood with BMI and cardiometabolic traits.

Methods
Analyses were conducted across the life course using the ARIES cohort of mothers (n = 792) and children (n = 906), for whom DNA methylation and genetic profiles and BMI at multiple time points (3 in children at birth, in childhood and in adolescence; 2 in mothers during pregnancy and in middle age) were available. Genetic and DNA methylation scores for BMI were derived using published associations between BMI and DNA methylation and genotype. Causal relationships between methylation and BMI were assessed using Mendelian randomisation and cross-lagged models.

Results
The DNA methylation scores in adult women explained 10% of extant BMI variance. However, less extant variance was explained by scores generated in the same women during pregnancy (2% BMI variance) and in older children (15–17 years; 3% BMI variance). Similarly, little extant variance was explained in younger children (at birth and at 7 years; 1% and 2%, respectively). These associations remained following adjustment for smoking exposure and education levels. The DNA methylation score was found to be a poor predictor of future BMI using linear and cross-lagged models, suggesting that DNA methylation variation does not cause later variation in BMI. However, there was some evidence to suggest that BMI is predictive of later DNA methylation. Mendelian randomisation analyses also support this direction of effect, although evidence is weak. Finally, we find that DNA methylation scores for BMI are associated with extant cardiometabolic traits independently of BMI and genetic score.

Conclusion
The age-specific nature of DNA methylation associations with BMI, lack of causal relationship and limited predictive ability of future BMI indicate that DNA methylation is likely influenced by BMI and might more accurately be considered a biomarker of BMI and related outcomes rather than a predictor. Future epigenome-wide association studies may benefit from further examining associations between early DNA methylation and later health outcomes.
Cortical ischaemic patterns in term partial-prolonged hypoxic-ischaemic injury—the inter-arterial watershed demonstrated through atrophy, ulegyria and signal change on delayed MRI scans in children with cerebral palsy
Authors: Chacko Anith , Andronikou Savvas , Mian Ali , Gonçalves Fabrício Guimarães , Vedajallam Schadie , Thai Ngoc Jade 
Published: March 2020

AbstractThe inter-arterial watershed zone in neonates is a geographic area without discernible anatomic boundaries and difficult to demarcate and usually not featured in atlases. Schematics currently used to depict the areas are not based on any prior anatomic mapping, compared to adults.Magnetic resonance imaging (MRI) of neonates in the acute to subacute phase with suspected hypoxic-ischaemic injury (HII) can demonstrate signal abnormality and restricted diffusion in the cortical and subcortical parenchyma of the watershed regions.In the chronic stage of partial-prolonged hypoxic-ischaemic injury, atrophy and ulegyria can make the watershed zone more conspicuous as a region. Our aim is to use images extracted from a sizable medicolegal database (approximately 2000 cases), of delayed MRI scans in children with cerebral palsy, to demonstrate the watershed region.To achieve this, we have selected cases diagnosed on imaging as having sustained a term pattern of partial-prolonged HII affecting the hemispheric cortex, based on the presence of bilateral, symmetric atrophy with ulegyria. From these, we have identified those patients demonstrating injury along the whole watershed continuum as well as those demonstrating selective anterior or posterior watershed predominant injury for demonstration.Recognition of this zone is essential for diagnosing partial-prolonged hypoxic-ischaemic injury sustained in term neonates. The images presented in this pictorial review provide a template for identifying the cortical watershed distribution when there is milder regional (anterior, parasagittal, peri-Sylvian and posterior) watershed injury and for more severe injury where multiple regions are injured in combination or as a continuum.
OTUB1-mediated deubiquitination of FOXM1 up-regulates ECT-2 to promote tumor progression in renal cell carcinoma
Authors: Zhou Kai , Mai Haixing , Zheng Song , Cai Weizhong , Yang Xu , Chen Zhenlin , Zhan Bin 
Published: March 2020

Abstract
Background
OTUB1 (ovarian tumor domain protease domain-containing ubiquitin aldehyde-binding proteins)-mediated deubiquitination of FOXM1 (Forkhead box M1) participates in carcinogenesis of various tumors. We aim to investigate the effect and mechanism of OTUB1/FOXM1 on RCC (renal cell carcinoma) progression. Expression levels of OTUB1 in RCC tissues and cell lines were examined by qRT-PCR (quantitative real-time polymerase chain reaction) and immunohistochemistry. Cell proliferation was measured with CCK8 (Cell Counting Kit-8) and colony formation assays. Wound healing and transwell assays were used to determine cell migration and invasion, respectively. The effect of OTUB1 on FOXM1 ubiquitination was examined by Immunoprecipitation. Western blot was used to uncover the underlying mechanism. In vivo subcutaneous xenotransplanted tumor model combined with immunohistochemistry and western blot were used to examine the tumorigenic function of OTUB1.

Results
OTUB1 was up-regulated in RCC tissues and cell lines, and was associated with poor prognosis of RCC patients. Knockdown of OTUB1 inhibited cell viability and proliferation, as well as migration and invasion of RCC cells. Mechanistically, knockdown of OTUB1 down-regulated FOXM1 expression by promoting its ubiquitination. Down-regulation of FOXM1 inhibited ECT2 (epithelial cell transforming 2)-mediated Rho signaling. Moreover, the inhibition of RCC progression caused by OTUB1 knockdown was reversed by FOXM1 over-expression. In vivo subcutaneous xenotransplanted tumor model also revealed that knockdown of OTUB1 could suppress in vivo RCC growth via down-regulation of FOXM1-mediated ECT2 expression.

Conclusions
OTUB1-mediated deubiquitination of FOXM1 up-regulates ECT-2 to promote tumor progression in RCC, providing a new potential therapeutic target for RCC treatment.