bluuebunny/crossref_metadata_2025_split huggingface dataset:
A meta‐analysis on association between CSN3 gene variants and milk yield and composition in cattle
Authors: Mahmoudi P. , Rostamzadeh J. , Rashidi A. , Zergani E. , Razmkabir M. 
Published: February 2020

SummaryA meta‐analysis on the effects of A and B alleles, the most frequent alleles of CSN3 gene, on milk yield and composition traits was conducted by pooling a large dataset consisting of 30 471 genotyped cattle. Four genetic models, comprising dominant (AA + AB vs. BB), recessive (AA vs. AB + BB), additive (AA vs. BB) and co‐dominant (AA + BB vs. AB), were employed to analyze data. Standardized mean difference (SMD) was used to measure the size of the effects of A and B alleles of CSN3 on studied traits. Effect sizes of 0.2, 0.5 and 0.8 represent small, medium and large effects, respectively. The results indicate that B allele, in the form of BB genotype, has a significant, but medium effect on lactation yield under dominant (SMD = 0.259, P‐value = 0.006) and additive (SMD = 0.279, P‐value = 0.035) models. Moreover, a small decrease in the fat percentage occurred in cows having A allele under dominant (SMD = −0.077, P‐value = 0.006) and additive (SMD = −0.106, P‐value = 0.035) models. Furthermore, CSN3 variants significantly but slightly affect protein percentage under dominant (SMD = −0.146, P‐value = 0.000), recessive (SMD = −0.077, P‐value = 0.000) and additive (SMD = −0.219, P‐value = 0.000) models, showing the negative effect of A allele on this trait. Meta‐analysis results reveal that daily milk yield is slightly affected by CSN3 variants under recessive (SMD = 0.056, P‐value = 0.033) and additive (SMD = 0.061, P‐value = 0.013) genetic models. There is no effect of CSN3 variants on either protein or fat yield. In addition, the effects of CSN3 variants on milk‐related traits were not observed under the co‐dominant model. Sensitivity and publication bias analyses were carried out to confirm the stability of meta‐analyses results.
Association of NE, leptin, and 5‐HT with electrophysiological parameters in patients with primary premature ejaculation
Authors: Xia Jiadong , Zhang Qijie , Wang Yamin , Luan Jiaochen , Yang Jie , Cong Rong , Wang Zengjun , Song Ninghong 
Published: February 2020

AbstractObjectiveTo investigate the possible role of serum norepinephrine (NE), leptin, and 5‐hydroxytryptamine (5‐HT) and their correlations with sympathetic skin response located in the penis (PSSR) in primary premature ejaculation (PPE).MethodsWe compared the serum level of NE, leptin, and 5‐HT, intravaginal ejaculatory latency time (IELT) and the premature ejaculation diagnostic tool (PEDT) scores between 57 PPE patients and 42 healthy control men as controls, who were recruited between September 2016 and January 2019. Additionally, the amplitude and latency of PSSR were measured and compared between the two groups.ResultsCompared with healthy men, both leptin and NE increased significantly in PPE patients (P = .003, P = .005), while serum 5‐HT remarkably decreased (P = .002). Serum leptin, NE, and 5‐HT were significantly correlated with the diagnosis of PPE, PSSR amplitude, and latency. Moreover, compared with single serum indicator, NE/5‐HT and leptin/5‐HT had a stronger correlation with both PSSR amplitude (r = .8377, P < .001; r = .9323, P < .001, respectively) and latency (r = −.8058, P < .001; r = −.8901, P < .001, respectively).ConclusionSignificant differences in leptin, NE, and 5‐HT are observed between PPE patients and the controls, which supports the hypothesis of hyperactive sympathetic nerve system (SNS) in PPE. Additionally, leptin/5‐HT ratio may serve as an ideal indicator for reflecting SNS activity and predicting treatment response in PPE patients in the future.
Laparoscopic‐endoscopic cooperative surgery for early gastric cancer with gastroesophageal varices
Authors: Namikawa Tsutomu , Iwabu Jun , Munekage Masaya , Uemura Sunao , Maeda Hiromichi , Kitagawa Hiroyuki , Nakayama Taku , Fukuhara Hideo , Inoue Keiji , Al‐Sheikh Mariam , Jaiswal Nalin , Kobayashi Michiya , Hanazaki Kazuhiro 
Published: February 2020

AbstractThis report describes a patient with early gastric cancer with gastroesophageal varices who underwent laparoscopic‐endoscopic cooperative surgery. The patient, a 75‐year‐old woman, was referred to our hospital for the treatment of gastric cancer. Esophagogastroduodenoscopy revealed a superficial spreading‐type tumor on the posterior wall of the upper third of the stomach that was very close to the gastric varices. Biopsy specimens showed a moderately differentiated tubular adenocarcinoma. Abdominal contrast‐enhanced CT showed an enhanced submucosal area with noticeably dilated veins around the perigastric region and no masses in the liver. The patient underwent local resection of the stomach using laparoscopic‐endoscopic cooperative surgery; this procedure was chosen because of the patient's risk of bleeding from the gastric varices in the area adjacent to the cancer during endoscopic submucosal dissection. Macroscopic examination of the resected specimen showed a superficial spreading lesion measuring 55 × 50 mm. The pathological diagnosis was moderately differentiated tubular adenocarcinoma invading the gastric submucosal layer without lymphovascular invasion.
Effects of the dual sodium–glucose linked transporter inhibitor, licogliflozin vs placebo or empagliflozin in patients with type 2 diabetes and heart failure
Authors: de Boer Rudolf A. , Núñez Julio , Kozlovski Plamen , Wang Yi , Proot Pieter , Keefe Deborah 
Published: February 2020

AimsExplore the efficacy, safety and tolerability of the dual sodium–glucose cotransporter (SGLT) 1 and 2 inhibitor, licogliflozin in patients with type‐2 diabetes mellitus (T2DM) and heart failure.MethodsThis multicentre, parallel‐group phase IIA study randomized 125 patients with T2DM and heart failure (New York Heart Association II–IV; plasma N‐terminal pro b‐type natriuretic peptide [NT‐proBNP] >300 pg/mL) to licogliflozin (2.5 mg, 10 mg, 50 mg) taken at bedtime, empagliflozin (25 mg) or placebo (44 patients completed the study). The primary endpoint was change from baseline in NT‐proBNP after 12 weeks. Secondary endpoints included change from baseline in glycated haemoglobin, fasting plasma glucose, weight, blood pressure, fasting lipid profile, high‐sensitivity c‐reactive protein, and safety and tolerability.ResultsLicogliflozin 10 mg for 12 weeks significantly reduced NT‐proBNP vs placebo (Geometric mean ratio 0.56 [95% confidence interval: 0.33, 0.95], P = .033). A trend was observed with 50 mg licogliflozin (0.64 [95% confidence interval: 0.40, 1.03], P = .064), with no difference between licogliflozin and empagliflozin. The largest numerical decreases in glycated haemoglobin were with licogliflozin 50 mg (−0.58 ± 0.34%) and empagliflozin (−0.44 ± 1.18%) vs placebo (−0.04 ± 0.91%). The reduction in body weight was similar with licogliflozin 50 mg (−2.15 ± 2.40 kg) and empagliflozin (−2.25 ± 1.89 kg). A numerical reduction in systolic blood pressure was seen with licogliflozin 50 mg (−9.54 ± 16.88 mmHg) and empagliflozin (−6.98 ± 15.03 mmHg) vs placebo (−2.85 ± 11.97 mmHg). Adverse events (AEs) were mild, including hypotension (6.5%), hypoglycaemia (8.1%) and inadequate diabetes control (1.6%). The incidence of diarrhoea (4.9%) was lower than previously reported.ConclusionThe reduction in NT‐proBNP with licogliflozin suggests a potential benefit of SGLT1 and 2 inhibition in patients with T2DM and heart failure.
First‐in‐human study with ACT‐539313, a novel selective orexin‐1 receptor antagonist
Authors: Kaufmann Priska , Anliker‐Ort Marion , Golor Georg , Kornberger Rüdiger , Dingemanse Jasper 
Published: February 2020

AimsThe orexin system is involved in anxiety behaviour and corresponding physiological reactions and constitutes a target for treatment of anxiety disorders. ACT‐539313 is a potent, selective orexin‐1 receptor antagonist being developed for the treatment of anxiety disorders. This first‐in‐human study investigated its single‐dose pharmacokinetics (PK) including food effect, pharmacodynamics (PD), safety and tolerability.MethodsThis double‐blind, placebo‐controlled, randomized study included 40 healthy male subjects. Ascending oral doses of 10–400 mg ACT‐539313 were investigated in 5 dose groups of 8 subjects (of whom 2 received placebo per dose group). At 100 mg, subjects received ACT‐539313 in fasted and fed conditions in a fixed sequential design. PK, PD (objective and subjective measures of sedation and effects on central nervous system), safety and tolerability were assessed.ResultsIn fasted conditions, ACT‐539313 was rapidly absorbed (median time to maximum plasma concentration [Cmax] 0.7–3.5 h) and cleared from plasma with a mean terminal half‐life of 3.3–5.7 h across dose levels. A 1.63‐fold (90% confidence interval: 1.26–2.11) increase in Cmax and no change in area under the concentration–time curve extrapolated to infinity was observed under fed compared to fasted conditions. No relevant PD signals were detected except for a trend of reduced saccadic peak velocity around time to Cmax. The most commonly reported adverse events were somnolence and headache. All adverse events were transient and of mild or moderate intensity. No treatment‐related effects on vital signs, clinical laboratory or 12‐lead electrocardiogram were observed.ConclusionsACT‐539313 exhibits good safety and tolerability at single doses of up to and including 400 mg that warrant further investigations.
Effect of ciclosporin on safety, lymphocyte kinetics and left ventricular remodelling in acute myocardial infarction
Authors: Cormack Suzanne , Mohammed Ashfaq , Panahi Pedram , Das Rajiv , Steel Alison J. , Chadwick Thomas , Bryant Andrew , Egred Mohaned , Stellos Konstantinos , Spyridopoulos Ioakim ,   the CAPRI investigators
Published: February 2020

AimsFollowing a favourable pilot trial using a single bolus of ciclosporin, it has been unclear why 2 large studies (CYCLE and CIRCUS) failed to prevent reperfusion injury and reduce infarct size in STEMI (ST elevation myocardial infarction). The purpose of this study was to assess the effect of ciclosporin on myocardial injury, left ventricular remodelling and lymphocyte kinetics in patients with acute STEMI undergoing primary percutaneous coronary intervention.MethodsIn this double‐blind, single centre trial, we randomly assigned 52 acute STEMI patients with an onset of pain of <6 hours and blocked culprit artery to a single bolus of ciclosporin (n = 26) or placebo (n = 26, control group) prior to reperfusion by stent percutaneous coronary intervention. The primary endpoint was infarct size at 12 weeks.ResultsMean infarct size at 12 weeks was identical in both groups (9.1% [standard deviation= 7.0] vs 9.1% [standard deviation = 7.0], P = .99; 95% confidence interval for difference: −4.0 to 4.1). CD3 T‐lymphocytes dropped to similar levels at 90 minutes (867 vs 852 cells/μL, control vs ciclosporin) and increased to 1454 vs 1650 cells/μL at 24 hours.ConclusionIn our pilot trial, a single ciclosporin bolus did not affect infarct size or left ventricular remodelling, matching the results from CYCLE and CIRCUS. Our study suggests that ciclosporin does either not reach ischaemic cardiomyocytes, or requires earlier application during first medical contact. Finally, 1 bolus of ciclosporin is not sufficient to inhibit CD4 T‐lymphocyte proliferation during remodelling. We therefore believe that further studies are warranted.(Evaluating the effectiveness of intravenous Ciclosporin on reducing reperfusion injury in pAtients undergoing PRImary percutaneous coronary intervention [CAPRI]; NCT02390674)
A semi‐mechanistic model based on glutathione depletion to describe intra‐individual reduction in busulfan clearance
Authors: Langenhorst Jurgen B. , Boss Jill , van Kesteren Charlotte , Lalmohamed Arief , Kuball Jürgen , Egberts Antoine C. G. , Boelens Jaap Jan , Huitema Alwin D. R. , van Maarseveen Erik M. 
Published: February 2020

AimTo develop a semi‐mechanistic model, based on glutathione depletion and predict a previously identified intra‐individual reduction in busulfan clearance to aid in more precise dosing.MethodsBusulfan concentration data, measured as part of regular care for allogeneic hematopoietic cell transplantation (HCT) patients, were used to develop a semi‐mechanistic model and compare it to a previously developed empirical model. The latter included an empirically estimated time effect, where the semi‐mechanistic model included theoretical glutathione depletion. As older age has been related to lower glutathione levels, this was tested as a covariate in the semi‐mechanistic model. Lastly, a therapeutic drug monitoring (TDM) simulation was performed comparing the two models in target attainment.ResultsIn both models, a similar clearance decrease of 7% (range −82% to 44%), with a proportionality to busulfan metabolism, was found. After 40 years of age, the time effect increased with 4% per year of age (0.6–8%, P = 0.009), causing the effect to increase more than a 2‐fold over the observed age‐range (0–73 years). Compared to the empirical model, the final semi‐mechanistic model increased target attainment from 74% to 76%, mainly through better predictions for adult patients.ConclusionThese results suggest that the time‐dependent decrease in busulfan clearance may be related to gluthathione depletion. This effect increased with older age (>40 years) and was proportional to busulfan metabolism. The newly constructed semi‐mechanistic model could be used to further improve TDM‐guided exposure target attainment of busulfan in patients undergoing HCT.
Effect of postdose fasting duration on hetrombopag olamine pharmacokinetics and pharmacodynamics in healthy volunteers
Authors: Yang Guoping , Huang Ranglang , Yang Shuang , Zhang Xingfei , Yang Xiaoyan , Chen Honghui , Huang Zhijun , Guo Chengxian , Pei Qi , Tai Yanfei , Shen Yancong , Huang Jie , Zou Chan 
Published: February 2020

AimsHetrombopag olamine is a novel small‐molecule, nonpeptide thrombopoietin receptor agonist developed for immune thrombocytopenia treatment. This study aims to determine the safety and the effect of fasting duration after administration of hetrombopag on pharmacokinetics and pharmacodynamics in Chinese healthy subjects.MethodsA randomized, open‐label, single‐dose, 3‐period crossover, self‐control trial was conducted. 15 eligible subjects were enrolled and received hetrombopag 7.5 mg at day 1 of each period followed by a standard meal 4 hours postdose (treatment A/fasting condition), or a high‐calorie, high‐fat meal 1 hour postdose (treatment B), or a high‐calorie, high‐fat meal 2 hours postdose (treatment C). The plasma concentrations of hetrombopag were determined by validated liquid chromatography–tandem mass spectrometry, platelet counts were quantified by blood test. Analysis was performed using a mixed model, including treatment, period as fixed effects and participant as a random effect.ResultsCompared with treatment A, peak concentration and area under concentration–time curve extrapolated to infinity decreased by 56 and 74.6%, and 44 and 61% in treatments B and C, respectively. The mean platelet number on day 6 increased by 15.8, 6.96 and 10.26%, respectively, in treatments A, B and C in comparison with baseline platelet level. No severe adverse events happened in any of the 3 treatments.ConclusionHetrombopag was well tolerated in healthy male subjects under fasted/fed conditions. The shorter fasting duration resulted in lower hetrombopag exposure, corresponding to a lower level of platelet elevation. Therefore, we recommended oral administration of hetrombopag on an empty stomach (fasting condition) or at least 2 hours before a meal to achieve maximum bioavailability.
Comparison of efficacy from two different dosing regimens of bortezomib: an exposure–response analysis
Authors: Parasrampuria Dolly A. , He Jianming , Zhang Liping , Muresan Bogdan , Hu Peter , Nemat Sepideh , Hashim Mahmoud , Lam Annette , Appiani Carlos , Cavo Michele , Dimopoulos Meletios A. , San‐Miguel Jesus , Mateos Maria‐Victoria 
Published: February 2020

SummaryBortezomib is a first‐in‐class proteasome inhibitor, approved for the treatment of multiple myeloma. The originally approved dosing schedule of bortezomib results in significant toxicities that require dose interruptions and discontinuations. Consequentially, less frequent dosing has been explored to optimise bortezomib’s benefit–risk profile. Here, we performed exposure–response analysis to compare the efficacy of the original bortezomib dosing regimen with less frequent dosing of bortezomib over nine 6‐week treatment cycles using data from the VISTA clinical trial and the control arm of the ALCYONE clinical trial. The relationship between cumulative bortezomib dose and clinical response was evaluated with a univariate logit model. The median cumulative bortezomib dose was higher in ALCYONE versus VISTA (42·2 vs. 38·5 mg/m2) and ALCYONE patients stayed on treatment longer (mean: 7·2 vs. 5·8 cycles). For all endpoints and regimens, probability of clinical response correlated with cumulative bortezomib dose. Similar to results observed for VISTA, overall survival was longer in ALCYONE patients with ≥ 39·0 versus < 39·0 mg/m2 cumulative dose (hazard ratio, 0·119; P < 0·0001). Less frequent bortezomib dosing results in comparable efficacy, and a higher cumulative dose than the originally approved bortezomib dosing schedule, which may be in part be due to reduced toxicity and fewer dose reductions/interruptions.
DPEP1 expression promotes proliferation and survival of leukaemia cells and correlates with relapse in adults with common B cell acute lymphoblastic leukaemia
Authors: Zhang Jia‐Min , Xu Yan , Gale Robert P. , Wu Li‐Xin , Zhang Jing , Feng Yong‐Huai , Qin Ya‐Zhen , Jiang Hao , Jiang Qian , Jiang Bin , Liu Yan‐Rong , Chen Yu‐Hong , Wang Yu , Zhang Xiao‐Hui , Xu Lan‐Ping , Huang Xiao‐Jun , Liu Kai‐Yan , Ruan Guo‐Rui 
Published: February 2020

SummaryDehydropeptidase‐1 (DPEP1) is a zinc‐dependent metalloproteinase abnormally expressed in many cancers. However, its potential role in adults with B cell acute lymphoblastic leukaemia (ALL) is unknown. We found that in adults with common B cell ALL high DPEP1, transcript levels at diagnosis were independently associated with an increased cumulative incidence of relapse (CIR) and worse relapse‐free survival (RFS) compared with subjects with low transcript levels. We show an increased proliferation and prosurvival role of DPEP1 in B cell ALL cells via regulation of phosphCREB and p53, which may be the biological basis of the clinical correlation we report. Our data implicate DPEP1 expression in the biology of common B cell ALL in adults. We report clinical correlates and provide a potential biological basis for these correlations. If confirmed, analysing DPEP1 transcript levels at diagnosis could help predict therapy outcomes. Moreover, regulation of DPEP1 expression could be a therapy target in B cell ALL.
Novel phenotype of syndromic premature ovarian insufficiency associated with TP63 molecular defect
Authors: Mathorne Stine W. , Ravn Pernille , Hansen Dorte , Beck‐Nielsen Signe S. , Gjørup Hans , Sørensen Kristina P. , Fagerberg Christina R. 
Published: February 2020

AbstractThere is growing evidence that TP63 is associated with isolated as well as syndromic premature ovarian insufficiency (POI). We report two adolescent sisters diagnosed with undetectable ovaries, uterine hypoplasia, and mammary gland hypoplasia. A novel paternally inherited nonsense variant in TP63 [NM_003722.4 c.1927C > T,p.(Arg643*)] in exon 14 was identified by exome sequencing. One of the syndromes linked to TP63 is limb mammary syndrome (LMS), an autosomal dominant inherited disorder characterized by ectrodactyly, hypoplasia of mammary‐gland and nipple, lacrimal duct stenosis, nail dysplasia, dental anomalies, cleft palate and/or cleft lip and absence of skin and hair defects. The TP63 variant segregated with symptoms of LMS in the family, however, no affected individual had limb defects. The phenotype reported here represents a novel syndromic phenotype associated with TP63. Reported cases with TP63 associated POI are reviewed.
Drinking contexts and their association with acute alcohol‐related harm: A systematic review of event‐level studies on adults' drinking occasions
Authors: Stevely Abigail K. , Holmes John , McNamara Simon , Meier Petra S. 
Published: February 2020

AbstractIssuesEvent‐level alcohol research can inform prevention efforts by determining whether drinking contexts—such as people or places—are associated with harmful outcomes. This review synthesises evidence on associations between characteristics of adults' drinking occasions and acute alcohol‐related harm.ApproachWe systematically searched Ovid MEDLINE, Ovid PsycInfo and the Web of Science Social Sciences Citation Index. Eligible papers used quantitative designs and event‐level data collection methods. They linked one or more drinking contexts to acute alcohol‐related harm. Following extraction of study characteristics, methods and findings, we assessed study quality and narratively synthesised the findings. PROSPERO ID: CRD42018119701.Key FindingsSearches identified 95 eligible papers, 65 (68%) of which study young adults and 62 (65%) of which are set in the United States, which limits generalisability to other populations. These papers studied a range of harms from assault to drink driving. Study quality is good overall although measures often lack validation. We found substantial evidence for direct effects of drinking context on harms. All of the contextual characteristics types studied (e.g. people, place, timing, psychological states, drink type) were consistently associated with harms. Certain contexts were frequently studied and associated with harms, in particular, weekend drinking, drinking in licensed premises and concurrent illicit drug use.ImplicationsThe findings of our review indicate target drinking contexts for prevention efforts that are consistently associated with increased acute alcohol‐related harm.ConclusionA large range of contextual characteristics of drinking occasions are directly associated with acute alcohol‐related harm, over and above levels of consumption.
Completeness of reporting of case reports in high‐impact medical journals
Authors: Calvache José A. , Vera‐Montoya Maira , Ordoñez Darío , Hernandez Adrian V. , Altman Douglas , Moher David 
Published: February 2020

AbstractIntroductionCase reports represent a relevant, timely and important study design in advancing medical scientific knowledge. They allow integration between clinical practice and clinical epidemiology. We aimed to assess the completeness of reporting (COR) of case reports published in high‐impact journals. We assessed the COR of case reports using the CARE guidelines.Materials and methodsWe selected three high‐impact journals and one journal specialized in publishing case reports, in which we included all published case reports from July to December 2017. Median COR score was calculated per study, and CORs were compared between journals with and without endorsement of CARE guidelines.ResultsOne hundred and fourteen case reports were included. Overall median COR was 81%, IQR [63%‐96%]. Sections with the highest COR (84%‐100%) were patient information, clinical findings, therapeutic intervention, follow‐up and outcomes, discussion and informed consent. Sections with the lowest COR were title, keywords, timeline and patient perspective (2%‐34%). COR was higher in journals endorsing in comparison to those not endorsing CARE guidelines (77% vs 65%), respectively, median difference = −12% 95% CI [−16% to −7%].DiscussionOverall completeness of case reports in included journals is high especially for CARE endorsing and dedicated journals but reporting of some items could be improved. Ongoing and future evaluations of endorsement status of reporting guidelines in medical journals should be assessed to improve completeness and reduce waste of clinical research, including case reports.