bluuebunny/crossref_metadata_2025_split huggingface dataset:
Placental extracellular vesicles and pre‐eclampsia
Authors: Schuster Jessica , Cheng Shi‐Bin , Padbury James , Sharma Surendra 
Published: July 2020

AbstractPre‐eclampsia is a hypertensive disease of pregnancy characterized by new‐onset hypertension, with either proteinuria and/or organ dysfunction. Pre‐eclampsia is a leading cause of maternal morbidity and mortality; however, the underlying cellular and molecular mechanisms are not well understood. There is consensus that the underlying mechanism(s) resulting in pre‐eclampsia is centered around abnormal placentation, inadequate spiral‐artery remodeling, and deficiency in trophoblast invasion, resulting in impaired maternal blood flow to the placenta and a release of signals and/or inflammatory mediators into maternal circulation triggering the systemic manifestations of pre‐eclampsia. ER stress, resulting in impaired autophagy and placental release of aggregated proteins, may also confer systemic stress to maternal organs in pre‐eclampsia. Extracellular vesicles (EVs), lipid‐bilayer enclosed structures containing macromolecules including proteins, miRNA, and other important nucleotides, have been suggested to play an important role in this maternal‐fetal communication. Circulating EVs are present in greater quantity in the plasma of pre‐eclampsia subjects compared to normal pregnancy, and the placental derived EVs have been shown to have altered protein and RNA cargo. In this review, we will focus on EVs and their role in pre‐eclampsia, specifically their role in immune responses, inflammation, altered angiogenesis, and endothelial dysfunction.
Compliance with follow‐up for patients with stage 1 testicular germ cell tumour
Authors: Cheung King Tung , Dat Anthony , Wong Peter , Dowling Caroline , Davis Ian D. , Sengupta Shomik 
Published: July 2020

AbstractBackgroundThis study aimed to evaluate the compliance and loss‐to‐follow‐up (LTFU) rate in patients with stage 1 testicular germ cell tumours (GCTs) on active surveillance protocol at a metropolitan health service in Melbourne, Australia.MethodsPatients with stage 1 testicular GCTs diagnosed between 30 June 2012 and 30 June 2018 were identified. Compliance of surveillance programme was classified into three groups: ‘adequate’, ‘missed appointment(s)’ or ‘LTFU’. The LTFU rate was assessed using Kaplan–Meier methodology. Log‐rank test was used for univariate analyses.ResultsForty‐eight patients had stage 1 testicular GCTs during the 6‐year period. Twenty‐two (46%) of them were managed with active surveillance and 26 (54%) of them were given adjuvant therapy. Compliance with active surveillance was assessed as adequate in 12 (55%), missed appointment(s) in six (27%) and LFTU in four (18%). The LTFU rates in patients with active surveillance at 12, 24 and 36 months were 9%, 9% and 19%, respectively. The LTFU rate in patients with active surveillance was not significantly different from patients who received adjuvant therapy (hazard ratio 0.71 (95% confidence intervals 0.22, 2.30), P = 0.56). Three (14%) of the 22 patients managed with active surveillance had recurrence of disease, all of which occurred in the first 12 months, compared to two (8%) of the 26 patients who had adjuvant therapy.ConclusionActive surveillance is a commonly utilized management option for stage 1 testicular GCTs, but has a LTFU rate of almost 20% that may limit its effectiveness. The recurrence rate was comparable to published literature.
The effect of miR‐10b on growth hormone in pituitary cells of Yanbian yellow cattle by somatostatin receptor 2
Authors: Ji Jiuxiu , Jin Taihua , Lou Angang , Zhang Rui , Chen Yingying , Xiang Siyu , Cui Changyan , Yu Longzheng , Guan Lizeng 
Published: July 2020

AbstractThis study aimed to evaluate the effect of miR‐10b on growth hormone (GH) in pituitary cells of Yanbian yellow cattle. According to analysis of GH and somatostatin receptor 2 (SSTR2) mRNA and protein expression levels, we found that miR‐10b targeted 3′UTR of SSTR2. Compared with the negative control (NC) group, GH mRNA transcription and protein expression in pituitary cells of Yanbian yellow cattle were significantly increased by adding miR‐10b mimics (p < .01), while these were significantly decreased by adding miR‐10b inhibitor (p < .05); compared with the NC group, SSTR2 mRNA transcription and protein expression were significantly inhibited by the addition of miR‐10b mimics (p < .01), while these were significantly increased by the addition of miR‐10b inhibitor compared with the iNC group (p < .05). This study suggested that miR‐10b could regulate GH level by regulating SSTR2 gene expression in pituitary cells of Yanbian yellow cattle.
Super‐mini percutaneous nephrolithotomy (PCNL) vs standard PCNL for the management of renal calculi of <2 cm: a randomised controlled study
Authors: Guddeti Raja Sekhar , Hegde Padmaraj , Chawla Arun , de la Rosette Jean J.M.C.H. , Laguna Pes Maria Pilar , Kapadia Aseem 
Published: July 2020

ObjectiveTo compare the effectiveness and safety of standard percutaneous nephrolithotomy (sPCNL) and super‐mini PCNL (SMP).Patients and MethodsA total of 150 patients presenting with renal calculi of <2 cm were randomised to either sPCNL (Group 1) or SMP (Group 2). Randomisation was based on centralised computer‐generated numbers. Variables studied included: stone‐free rates (SFRs), operative time, intra‐ and postoperative complications, postoperative pain score, analgesic requirement, and hospital stay. Statistical analysis was performed using at‐test or Mann–WhitneyU‐test for continuous variables and chi‐squared test or Fisher’s exact test for categorical variables.ResultsBetween September 2018 and April 2019, 75 patients were included in each group. The SFRs of the groups were similar (97.33 vs 98.66%,P= 0.56). The mean (sd)operative time was significantly longer in Group 2, at 36.40 (14.07) vs 23.12 (11.96) min (P< 0.001). The mean (sd)decrease in haemoglobin was significantly less in Group 2, at 3.0 (4.9) vs 7.5 (6.5) g/L (P< 0.001). The mean (sd)pain score at 24 h was significantly lower in Group 2, at 0.3 (0.46) vs 0.75 (0.53) (P< 0.001). The mean (sd)analgesic requirement was significantly less in Group 2, at 67 (22.49) vs 91.5 (30.56) mg tramadol (P< 0.001). The mean (sd) hospital stay was significantly less in Group 2, at 28.38 (3.6) vs 39.84 (3.7) h (P< 0.001).ConclusionsSMP is equally as effective as sPCNL for managing renal calculi of <2 cm, with improved safety. Although SMP is associated with a longer operative time, it has a significantly lower incidence of bleeding and postoperative pain, and a shorter hospital stay.
Biology and grading of pleomorphic xanthoastrocytoma—what have we learned about it?
Authors: Vaubel Rachael , Zschernack Valentina , Tran Quynh T. , Jenkins Sarah , Caron Alissa , Milosevic Dragana , Smadbeck James , Vasmatzis George , Kandels Daniela , Gnekow Astrid , Kramm Christof , Jenkins Robert , Kipp Benjamin R. , Rodriguez Fausto J. , Orr Brent A. , Pietsch Torsten , Giannini Caterina 
Published: July 2020

AbstractPleomorphic xanthoastrocytoma (PXA) is a rare astrocytoma predominantly affecting children and young adults. We performed comprehensive genomic characterization on a cohort of 67 patients with histologically defined PXA (n = 53, 79%) or anaplastic PXA (A‐PXA, n = 14, 21%), including copy number analysis (ThermoFisher Oncoscan, n = 67), methylation profiling (Illumina EPIC array, n = 43) and targeted next generation sequencing (n = 32). The most frequent alterations were CDKN2A/B deletion (n = 63; 94%) and BRAF p.V600E (n = 51, 76.1%). In 7 BRAF p.V600 wild‐type cases, alternative driver alterations were identified involving BRAF, RAF1 and NF1. Downstream phosphorylation of ERK kinase was uniformly present. Additional pathogenic alterations were rare, with TERT, ATRX and TP53 mutations identified in a small number of tumors, predominantly A‐PXA. Methylation‐based classification of 46 cases utilizing a comprehensive reference tumor allowed assignment to the PXA methylation class in 40 cases. A minority grouped with the methylation classes of ganglioglioma or pilocytic astrocytoma (n = 2), anaplastic pilocytic astrocytoma (n = 2) or control tissues (n = 2). In 9 cases, tissue was available from matched primary and recurrent tumors, including 8 with anaplastic transformation. At recurrence, two tumors acquired TERT promoter mutations and the majority demonstrated additional non‐recurrent copy number alterations. Methylation class was preserved at recurrence. For 62 patients (92.5%), clinical follow‐up data were available (median follow‐up, 5.4 years). Overall survival was significantly different between PXA and A‐PXA (5‐year OS 80.8% vs. 47.6%; P = 0.0009) but not progression‐free survival (5‐year PFS 59.9% vs. 39.8%; P = 0.05). WHO grade remained a strong predictor of overall survival when limited to 38 cases defined as PXA by methylation‐based classification. Our data confirm the importance of WHO grading in histologically and epigenetically defined PXA. Methylation‐based classification may be helpful in cases with ambiguous morphology, but is largely confirmatory in PXA with well‐defined morphology.
DNA methylation down‐regulates integrin β4 expression in asthmatic airway epithelial cells
Authors: Wu Mengping , Yang Yu , Yuan Lin , Yang Ming , Wang Leyuan , Du Xizi , Qin Ling , Wu Shuangyan , Xiang Yang , Qu Xiangping , Liu Huijun , Qin Xiaoqun , Liu Chi 
Published: July 2020

AbstractBackgroundIntegrin β4 (ITGB4) is a hemi‐desmosome protein which is downregulated in the airway epithelial cells of asthma patients. The proximal promoters and exons of ITGB4 contain CpG islands or multiple CpG sites both in human and mice, which indicated the possible methylation regulation of ITGB4 in airway epithelial cells.ObjectiveWe sought to unveil that DNA methylation regulates the decreased ITGB4 during the pathogenesis of asthma.MethodsMice were exposed to house dust mite (HDM) extracts to construct an asthma model. 5‐Aza‐2'‐deoxycytidine (5‐AZA) or dexamethasone (DEX) were added in the last two weeks. Besides, the primary human bronchial epithelial (HBE) cells were incubated for the detection of ITGB4 expression and methylation status after HDM stress. Furthermore, DNA methylation of ITGB4 in peripheral blood was measured in asthma patients. Logistic regression was employed to evaluate the association between methylation sites and asthma patients’ ages in the control of potential confounders. Moreover, the correlations between differentially methylated sites (DMSs) and clinical parameters in asthma patients were assessed. Finally, the ability of candidate DMSs to predict asthma was evaluated by receiver operating characteristic (ROC) analysis and principal component analysis (PCA).ResultsWe found that in HDM‐stressed asthma model, DNA methylation regulated the reduced ITGB4 expression in airway epithelial cells. Moreover, alteration in the specific CpG sites (chr17:73717720 and chr17:73717636) of ITGB4 may regulate ITGB4 expression and further may be associated with the clinically phenotypic of asthma. The specific DMSs of ITGB4 in peripheral blood can distinguish asthma patients from healthy controls (HCs) effectively.Conclusions and Clinical RelevanceThis study confirmed that DNA methylation regulates the decreased expression of ITGB4 in the airway epithelial cells of asthma patients. These results supply some useful insights to the mechanism of the decreased ITGB4 in asthmatic airway epithelial and provide possible targets for early prediction and screening of asthma.
What is being revealed in 2020?
Authors: Bloomquist Karen L. 
Published: July 2020

AbstractThe Covid‐19 pandemic is exposing how humans have long related to nature, and revealing aspects of classism and racism that have long been ignored. Drawing on spiritual resources, such as Luther, might the polarizing, self versus other tendencies be overcome and the long pandemic rooted in economic class and racism more effectively addressed today? Can this result in a “new normal”?
The effect of referral to an open‐group behavioural weight‐management programme on the relative risk of normoglycaemia, non‐diabetic hyperglycaemia and type 2 diabetes: Secondary analysis of the WRAP trial
Authors: Ahern Amy L. , Griffin Simon J. , Wheeler Graham M. , Sharp Stephen J. , Aveyard Paul , Boyland Emma J. , Halford Jason C. G. , Jebb Susan A. 
Published: July 2020

AbstractAimTo examine the impact of open‐group behavioural weight‐management programmes on the risk of diabetes among those with a body mass index (BMI) of ≥28 kg/m2 and those with non‐diabetic hyperglycaemia (NDH).MethodsThis was a secondary analysis of data from the WRAP trial, in which participants (N = 1267; aged ≥18 years, BMI ≥ 28 kg/m2) were randomized to brief intervention (BI; self‐help booklet), a weight‐management programme (WW; formerly Weight Watchers) for 12 weeks, or WW for 52 weeks. We used multinomial logistic regression to examine the effect of intervention group on the risk of hyperglycaemia and diabetes at 12 months in all participants with glycaemic status at both time points (N = 480; 38%) and those with NDH at baseline (N = 387; 31%). We used mixed effects models and linear fixed effects models to examine the effect of intervention group on body weight and HbA1c at 12 months in people with NDH.ResultsThere was a 61% relative reduction in the risk of NDH at the 12‐month follow‐up (12 weeks vs. BI: relative risk ratio [RRR] = 0.39 [95% CI 0.18, 0.87], P = .021; 52 weeks vs. BI: RRR = 0.38 [95% CI 0.17, 0.86], P = .020). For intervention effects on the risk of diabetes, confidence intervals were wide and overlapped 1 [12 weeks vs. BI: RRR = 0.49 [95% CI 0.12, 1.96], P = .312; 52 weeks vs. BI: RRR = 0.40 [95% CI 0.10, 1.63], P = .199). Participants with hyperglycaemia at baseline in the weight‐management programme were more probable to have normoglycaemia at the 12‐month follow‐up [12‐week programme vs. BI: RRR = 3.57 [95% CI 1.24, 10.29], P = .019; 52‐week programme vs. BI: RRR = 4.14 [95% CI 1.42, 12.12], P = .009).ConclusionsOpen‐group behavioural weight‐management programmes can help to prevent the development of NDH in people with overweight and obesity and to normalize glycaemia in people with NDH.
Cardiovascular and renal outcomes by baseline albuminuria status and renal function: Results from the LEADER randomized trial
Authors: Mosenzon Ofri , Bain Stephen C. , Heerspink Hiddo J. L. , Idorn Thomas , Mann Johannes F. E. , Persson Frederik , Pratley Richard E. , Rasmussen Søren , Rossing Peter , von Scholten Bernt Johan , Raz Itamar ,   LEADER Trial Investigators
Published: July 2020

AbstractAimTo assess cardiorenal outcomes by baseline urinary albumin‐to‐creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) in the contemporary LEADER cohort.Materials and methodsLEADER was a multinational, double‐blind trial. Patients with type 2 diabetes and high cardiovascular (CV) risk were randomized 1:1 to the glucagon‐like peptide‐1 analogue liraglutide (≤1.8 mg daily; n = 4668) or placebo (n = 4672) plus standard care and followed for 3.5 to 5 years. Primary composite outcomes were time to first non‐fatal myocardial infarction, non‐fatal stroke or CV death. Post hoc Cox regression analyses of outcomes by baseline UACR and eGFR subgroups were conducted with adjustment for baseline variables.ResultsIn the LEADER population, 1598 (17.5%), 2917 (31.9%), 1200 (13.1%), 1611 (17.6%), 845 (9.2%) and 966 (10.6%) had UACR = 0, >0 to <15, 15 to <30, 30 to <100, 100 to <300 and ≥300 mg/g, respectively. Increasing UACR and decreasing eGFR were linked with higher risks of the primary outcome, heart failure hospitalization, a composite renal outcome and death (P‐values for the Cochran‐Armitage test for trends were all <.0001). Across UACR and eGFR subgroups, risks of cardiorenal events and death were generally lower or similar with liraglutide versus placebo.ConclusionsIn a contemporary type 2 diabetes population, increasing baseline UACR and declining eGFR were linked with higher risks of cardiorenal events and death.
Practical use of insulin degludec/insulin aspart in a multinational setting: beyond the guidelines
Authors: Mehta Roopa , Chen Roger , Hirose Takahisa , John Mathew , Kok Adri , Lehmann Roger , Unnikrishnan Ambika Gopalakrishnan , Yavuz Dilek Gogas , Fulcher Gregory 
Published: July 2020

AbstractInsulin degludec/insulin aspart (IDegAsp) is a fixed‐ratio co‐formulation of insulin degludec, which provides long‐lasting basal insulin coverage, and insulin aspart, which targets postprandial glycaemia. This review provides expert opinion on the practical clinical use of IDegAsp, including: dose timings relative to meals, when and how to intensify treatment from once‐daily (OD) to twice‐daily (BID) dose adjustments, and use in special populations (including hospitalized patients). IDegAsp could be considered as one among the choices for initiating insulin treatment, preferential to starting on basal insulin alone, particularly for people with severe hyperglycaemia and/or when postprandial hyperglycaemia is a major concern. The recommended starting dose of IDegAsp is 10 units with the most carbohydrate‐rich meal(s), followed by individualized dose adjustments. Insulin doses should be titrated once weekly in two‐unit steps, guided by individualized fasting plasma glucose targets and based on patient goals, preferences and hypoglycaemia risk. Options for intensification from IDegAsp OD are discussed, which should be guided by HbA1c, prandial glucose levels, meal patterns and patient preferences. Recommendations for switching to IDegAsp from basal insulin, premixed insulins OD/BID, and basal‐plus/basal–bolus regimens are discussed. IDegAsp can be co‐administered with other antihyperglycaemic drugs; however, sulphonylureas frequently need to be discontinued or the dose reduced, and the IDegAsp dose may need to be decreased when sodium‐glucose co‐transporter‐2 inhibitors or glucagon‐like peptide‐1 receptor agonists are added. Considerations around the initiation or continuation of IDegAsp in hospitalized individuals are discussed, as well as in those undergoing medical procedures.
Left ventricular ejection fraction using manual and semi‐automated biplane method of discs in very preterm infants
Authors: Phad Nilkant , de Waal Koert 
Published: July 2020

AbstractBackgroundBiplane left ventricular ejection fraction (LVEF) is a valuable echocardiographic parameter for assessment of LV systolic pump efficiency in adults and children, but not often reported in preterm infants. The primary aim of this study was to longitudinally measure biplane LVEF in very preterm infants during the neonatal intensive care period. Secondary aim was to compare manual and semi‐automatic determination of LVEF for agreement and variability.MethodsStable preterm infants less than 30 weeks gestation were scanned on day 3, day 28, and at 36 weeks postmenstrual age. The LV endocardium was traced manually and semi‐automatically using integrated speckle tracking software in apical 4‐chamber and apical 3‐chamber images to obtain end‐diastolic volume and end‐systolic volume, and calculate LVEF. Agreement between methods and variability within and between observers was determined using an interclass correlation coefficient (ICC) and Bland‐Altman analysis.ResultsSixty‐six preterm infants with a mean birth weight of 1100 (239) g were analyzed. The average manual biplane LVEF was 58 (3)%, 59 (3)%, and 55 (4)% at the three respective time points. Manual LVEF showed good agreement with semi‐automatic LVEF (ICC 0.76) with a small bias of −1.5 (3.0)%. Interobserver variability of LVEF improved with semi‐automatic tracing of the LV endocardial border (ICC manual 0.68 vs semi‐automatic 0.80).ConclusionLeft ventricular systolic pump efficiency in preterm infants remains stable during the neonatal intensive care period. Semi‐automatic biplane LVEF has less interobserver variability and can be used interchangeably with manual biplane LVEF.
Distinct neural correlates of social and object reward seeking motivation
Authors: Dubey Indu , Georgescu Alexandra L. , Hommelsen Maximilian , Vogeley Kai , Ropar Danielle , Hamilton Antonia F. de C. 
Published: July 2020

AbstractThe “Choose‐a‐Movie‐CAM” is an established task to quantify the motivation for seeking social rewards. It allows participants to directly assess both the stimulus value and the effort required to obtain it. In the present study, we aimed to identify the neural mechanisms of such cost‐benefit decision‐making. To this end, functional Magnetic Resonance Imaging data were collected from 24 typical adults while they completed the CAM task. We partly replicated the results from our previous behavioural studies showing that typical adults prefer social over object stimuli and low effort over higher effort stimuli but found no interaction between the two. Results from neuroimaging data suggest that there are distinct neural correlates for social and object preferences. The precuneus and medial orbitofrontal cortex, two key areas involved in social processing are engaged when participants make a social choice. Areas of the ventral and dorsal stream pathways associated with object recognition are engaged when making an object choice. These activations can be seen during the decision phase even before the rewards have been consumed, indicating a transfer the hedonic properties of social stimuli to its cues. We also found that the left insula and bilateral clusters in the inferior occipital gyrus and the inferior parietal lobule were recruited for increasing effort investment. We discuss limitations and implications of this study which reveals the distinct neural correlates for social and object rewards, using a robust behavioural measure of social motivation.
The anterior insular cortex in the rat exerts an inhibitory influence over the loss of control of heroin intake and subsequent propensity to relapse
Authors: Joshi Dhaval D. , Puaud Mickaël , Fouyssac Maxime , Belin‐Rauscent Aude , Everitt Barry , Belin David 
Published: July 2020

AbstractThe anterior insular cortex (AIC) has been implicated in addictive behaviour, including the loss of control over drug intake, craving and the propensity to relapse. Evidence suggests that the influence of the AIC on drug‐related behaviours is complex as in rats exposed to extended access to cocaine self‐administration, the AIC was shown to exert a state‐dependent, bidirectional influence on the development and expression of loss of control over drug intake, facilitating the latter but impairing the former. However, it is unclear whether this influence of the AIC is confined to stimulant drugs that have marked peripheral sympathomimetic and anxiogenic effects or whether it extends to other addictive drugs, such as opiates, that lack overt acute aversive peripheral effects. We investigated in outbred rats the effects of bilateral excitotoxic lesions of AIC induced both prior to or after long‐term exposure to extended access heroin self‐administration, on the development and maintenance of escalated heroin intake and the subsequent vulnerability to relapse following abstinence. Compared to sham surgeries, pre‐exposure AIC lesions had no effect on the development of loss of control over heroin intake, but lesions made after a history of escalated heroin intake potentiated escalation and also enhanced responding at relapse. These data show that the AIC inhibits or limits the loss of control over heroin intake and propensity to relapse, in marked contrast to its influence on the loss of control over cocaine intake.