bluuebunny/crossref_metadata_2025_split huggingface dataset:
Downregulation of CCNA2 disturbs trophoblast migration, proliferation, and apoptosis during the pathogenesis of recurrent miscarriage
Authors: Li Xiao , Ma Xiao‐Ling , Tian Fu‐Ju , Wu Fan , Zhang Jing , Zeng Wei‐Hong , Lin Yi , Zhang Yan 
Published: May 2019

AbstractProblemRecurrent miscarriage (RM) is defined as two or more pregnancy losses until 24 weeks of gestation, which distresses up to 1‐5% of couples worldwide. Cyclin A2 (CCNA2) regulates the cell cycle by promoting transition through G1/S and G2/M. Little is known about CCNA2’s functions in trophoblast, although it is highly expressed in the placenta. We therefore sought to explore the role of CCNA2 in RM and early pregnancy.Method of studyFirst‐trimester human placental tissues were collected from patients with RM and normal pregnant women to clarify the expression level of CCNA2. First‐trimester human villi explants culture was performed as an ex vivo model to study the functions of CCNA2. The HTR8/SVneo cells were studied for in vitro experiments. The migration, proliferation, and apoptosis levels of trophoblast were examined in the CCNA2‐knockdown and CCNA2‐overexpressing HTR8 cells.ResultsOur study revealed that CCNA2 was downregulated in trophoblast of RM first‐trimester villi. Results showed that CCNA2 promotes migration of HTR8 cells via the RhoA‐ROCK signaling and that CCNA2 increased HTR8 proliferation and inhibited their apoptosis via p53 pathway. In addition, the relationship between ROCK signaling and p53 pathway was found. Further, mechanistic research attributed the regulatory function of CCNA2 on p53 pathway to the involvement of DNA damage.ConclusionOur study revealed the downregulation of CCNA2 in first‐trimester chorionic villi of patients with RM and showed that this protein regulates migration, proliferation, and apoptosis in HTR8 cells, suggesting that CCNA2 may be the potential therapeutic target for RM.
Health economic implications of postoperative complications following liver resection surgery: a systematic review
Authors: Cosic Luka , Ma Ronald , Churilov Leonid , Nikfarjam Mehrdad , Christophi Christopher , Weinberg Laurence 
Published: May 2019

BackgroundLimited data exists concerning the health economics of liver resection, with even less information on the costs emerging from complications, despite this remaining an important target from a health economic perspective. Our objective was to describe the financial burden of complications following liver resection.MethodsWe conducted a systematic search and included studies reporting resource use of in‐hospital complications during the index liver resection admission. All indications for liver resection were considered. All techniques were considered. Data was collected using a data extraction table and a narrative synthesis was performed.ResultsWe identified 12 eligible articles. There was considerable heterogeneity in study designs, patient populations and outcome definitions. We found weak evidence of increased costs associated with major liver resection compared to minor resections. We found robust evidence supporting the increasing economic burden arising from complications after liver resection. Acceptable evidence for increased cost due to the presence and grade of complication was found. Strong evidence concerning the association of length of stay with costs was demonstrated.ConclusionsThe presence and grade of complications increase hospital cost across diverse settings. The costing methodology should be transparent and complication grading systems should be consistent in future studies.
Morphology and severity of peri‐implantitis bone defects
Authors: Monje Alberto , Pons Ramón , Insua Angel , Nart José , Wang Hom‐Lay , Schwarz Frank 
Published: May 2019

AbstractBackgroundPeri‐implant defect morphology has shown to potentially impact upon the reconstructive outcomes for the management of peri‐implantitis. Given the role that defect morphology plays upon the decision‐making in the treatment of peri‐implantitis, the present study aimed at assessing the morphology and severity of peri‐implantitis bone defects and to insight on the patient‐, implant‐ and site‐related variables associated to these.Material and MethodsA cone‐beam computed tomography study was carried out to classify peri‐implantitis defects according to the type of defect, number of remaining bony walls and severity according to the extension of vertical bone loss. Three major defect categories were proposed: class I—infraosseous; class II—horizontal; class III—combined of class I and II. These were then subclassified into: (a) dehiscence; (b) 2/3‐wall; and (c) circumferential—type defect. According to the severity the defects were further subclassified into: A: advanced; M: moderate; and S: slight. In addition, 20 site‐, implant‐, and patient‐related variables were analyzed by generalized estimating equations (GEEs) of multilevel logistic regression models.ResultsBased on an a priori power calculation, 332 implants were screened in 47 peri‐implantitis patients. Of these, 158 peri‐implantitis implants were eligible. The most prevalent defect morphology type was class Ib (55%) followed by class Ia (16.5%), and class IIIb (13.9%). On the contrary, the less frequent defect was class II (1.9%). The most frequent degree of severity was M (50.6%) with S (10.1%) being the least prevalent. Buccal bone loss was significantly greater compared to the other bony walls in class I and class III defects. Age was associated with the type of defect. Age and smoking habit were associated with the morphology of the defects, while smoking habit, type of prosthesis and distance to adjacent implant were associated with the severity of the defects (vertical bone loss).ConclusionPeri‐implantitis defects frequently course with an infraosseous component and often with buccal bone loss. Certain patient‐, implant‐, and site‐specific variables are related with defect morphology and severity. However, morphological patterns for peri‐implantitis bone defects could not be proven (NCT NCT03777449).
Pulmonary oxygen uptake on‐kinetics can predict acute physiological responses to resistance exercise training in healthy young men
Authors: Kubo Yusuke , Fujita Daisuke , Sugiyama Shuhei , Hosokawa Masato , Nishida Yusuke 
Published: May 2019

SummaryPurposeTo clarify whether pulmonary oxygen uptake kinetics () at the onset of moderate‐intensity exercise can predict acute physiological responses to resistance exercise training (RET).MethodsWe investigated the relationship between and acute metabolic and hemodynamic responses to a single RET session in 27 healthy young adult men. Cardiopulmonary exercise was on a cycle ergometer, and a single RET at 30% or 60% of one‐repetition maximum was on a bilateral leg‐extension machine. We measured the anaerobic threshold, peak and while cardiopulmonary exercising, and the rates of increase in blood lactate (Bla), heart rate (HR), systolic blood pressure (SBP) and rate pressure product (RPP) for a single RET.ResultsThere were significant positive associations between and the rates of increase in Bla, HR, SBP and RPP during a single RET session (P<0·05). However, the anaerobic threshold and peak did not significantly affect these parameters.ConclusionThe is a useful evaluation index for predicting acute physiological responses to RET.
Pancreas size and exocrine function is decreased in young children with recent‐onset Type 1 diabetes
Authors: Augustine P. , Gent R. , Louise J. , Taranto M. , Penno M. , Linke R. , Couper J. J. ,   the ENDIA Study Group
Published: May 2019

AbstractAimsTo measure pancreatic area and exocrine function in young children with recent‐onset Type 1 diabetes to determine whether the exocrine pancreas is also affected in the pathophysiology of early childhood diabetes.MethodsThirty‐two children (14 boys) aged 5.5 (4.5, 7.3) median (IQR) years presenting with recent‐onset Type 1 diabetes and 90 controls (44 boys) of similar age had ultrasound imaging of the pancreas. Children with Type 1 diabetes were receiving insulin and were without ketosis. Transverse and longitudinal areas of the pancreas were measured by digitalized outline. Pancreatic faecal elastase‐1 was analysed using an enzyme‐linked immunosorbent assay kit in recent‐onset Type 1 diabetes and 38 first‐degree relative control children.ResultsPancreatic area and exocrine function were reduced in Type 1 diabetes. Mean transverse area (SD) in Type 1 diabetes was 6.82 cm2 (1.61) vs. 8.31 cm2 (1.74) in controls, adjusted estimate (95% CI) 1.45 (‐2.12, ‐0.79), P < 0.001; longitudinal area was 1.28 cm2 (0.44) vs. 1.55 cm2 (0.43), adjusted estimate (95% CI) ‐0.27 (‐0.45, ‐0.09), P = 0.003. Faecal elastase‐1 levels in Type 1 diabetes were 455 (323, 833) ug/g, median (IQR) vs. 1408 μg/g (1031, 1989) in controls, P < 0.001.ConclusionPancreatic area and accompanying subclinical exocrine function were reduced in very young children with recent‐onset Type 1 diabetes. This supports changes in the exocrine pancreas in the pathophysiology of Type 1 diabetes presenting in early life.
Quantification of pulmonary/systemic shunt ratio by single‐acquisition phase‐contrast cardiovascular magnetic resonance
Authors: Dunn Terence Sean , Patel Pratik , Abazid Bassem , Nagaraj Hosakote M. , Desai Ravi V. , Gupta Himanshu , Lloyd Steven G. 
Published: May 2019

AbstractPurposePhase‐contrast cardiovascular magnetic resonance (PC‐CMR) quantification of intracardiac shunt (measuring the pulmonary to systemic flow ratio, Qp/Qs) is typically determined by measuring flow through planes perpendicular the pulmonary trunk (PA) and ascending aorta (Ao). This method is subject to error from presence of background velocity offsets and requires two scan acquisitions. We evaluated an alternate PC‐CMR technique for quantifying Qp/Qs using a single modified plane that encompasses both the PA and Ao.Material and MethodsIn 53 patients evaluated for intracardiac shunting, PC‐CMR measurement in the individual Ao and PA planes and also in a single‐acquisition plane was obtained and Qp/Qs calculated by each method. Bland–Altman analysis was performed to evaluate the agreement between the two methods.ResultsThe 95% confidence limits of agreement ranged from −0.52 to +0.34 indicating good agreement between the two methods. There was excellent agreement on the clinically relevant threshold value of Qp/Qs ratio of 1.5 (representing criteria for surgical correction of shunt).ConclusionsQp/Qs determined from the single‐acquisition approach agrees well with that of the individual PA and Ao method and offers potential improved accuracy (due to background velocity offset).
Behaviour before beauty: Signal weighting during mate selection in the butterfly Papilio polytes
Authors: Westerman Erica L. , Antonson Nicholas , Kreutzmann Sydney , Peterson Alexandra , Pineda Skyy , Kronforst Marcus R. , Olson‐Manning Carrie F. 
Published: May 2019

AbstractMating displays often contain multiple signals. Different combinations of these signals may be equally successful at attracting a mate, as environment and signal combination may influence relative signal weighting by choosy individuals. This variation in signal weighting among choosy individuals may facilitate the maintenance of polymorphic displays and signalling behaviour. One group of animals known for their polymorphic patterning are Batesian mimetic butterflies, where the interaction of sexual selection and predation pressures is hypothesized to influence the maintenance of polymorphic wing patterning and behaviour. Males in the female‐limited polymorphic Batesian mimetic butterfly Papilio polytes use female wing pattern and female activity levels when determining whom to court. They court stationary females with mimetic wing patterns more often than stationary females with non‐mimetic, male‐like wing patterns and active females more often than inactive females. It is unclear whether females modify their behaviour to increase (or decrease) their likelihood of receiving male courtship, or whether non‐mimetic females spend more time in cryptic environments than mimetic females, to compensate for their lack of mimicry‐driven predation protection (at the cost of decreased visibility to males). In addition, relative signal weighting of female wing pattern and activity to male mate selection is unknown. To address these questions, we conducted a series of observational studies of a polymorphic P. polytes population in a large butterfly enclosure. We found that males exclusively courted active females, irrespective of female wing pattern. However, males did court active non‐mimetic females significantly more often than expected given their relative abundance in the population. Females exhibited similar activity levels, and selected similar resting environments, irrespective of wing pattern. Our results suggest that male preference for non‐mimetic females may play an active role in the maintenance of the non‐mimetic female form in natural populations, where males are likely to be in the presence of active, as well as inactive, mimetic and non‐mimetic females.
Can we use psychoactive drugs to treat pruritus?
Authors: Reszke Radomir , Szepietowski Jacek C. 
Published: May 2019

AbstractPruritus is a frequent complaint both in dermatology and general medicine. This burdensome symptom has a complex and multifactorial pathogenesis, with the key involvement of central nervous system in its development. Psychoactive drugs (psychopharmaceuticals) encompass several therapeutic groups utilized mainly in psychiatry. However, these drugs are occasionally used in dermatological practice and may contribute to alleviation of pruritus in a variety of cutaneous and extracutaneous disorders. This review article summarizes the role of H1‐antihistamines, antidepressants, antipsychotics and antiepileptics in managing pruritus.
The Effect of Shareholder Approval of Equity Issuances Around the World
Authors: Holderness Clifford G. 
Published: May 2019

Mandatory shareholder approval of equity issuances varies considerably across and within countries. In the United States and a few other countries, management typically needs the approval of only its board of directors to issue common stock. In most countries, however, by law or stock exchange rule, shareholders must vote to approve equity issuances when using certain methods or contemplating offers that exceed a specified fraction of outstanding shares. In some countries, shareholders must approve all equity issuances. Even in the United States, shareholder approval is mandatory under certain circumstances.The differences in the stock market reaction to shareholder‐approved equity issuances and to issues undertaken unilaterally by management are strikingly and consistently large. When shareholders approve stock issuances, whether public or rights offerings, or private placements, the average announcement returns are significantly positive, on the order of 2%. But when managers issue stock without shareholder approval, as in the case of U.S. public offerings, returns are significantly negative and 4% lower, on average, than for shareholder‐approved issues. What's more, the closer in time the shareholder vote is to the issue date, and the greater the required plurality (say, two‐thirds instead of half the vote required for approval), the more positive is the market reaction to the issue—and these findings hold for each of the three main kinds of offerings that take place in all 23 countries in the author's sample.Also telling, in countries where shareholder approval is required, such as Sweden and Malaysia, rights offers predominate over public issues. But in countries like the U.S. and Japan, where managers may generally issue stock without shareholder approval, public offers predominate over rights issues. These findings suggest that agency problems—the tendency of corporate managements to put their own interests before their shareholders'—play a major role in equity issuances. Such findings are also largely inconsistent with the adverse selection, market timing, and signaling explanations that currently dominate academic thinking about equity issuances by public corporations.
The Early Returns to International Hedge Fund Activism: 2000–2010
Authors: Becht Marco , Franks Julian , Grant Jeremy , Wagner Hannes 
Published: May 2019

In this summary of their recent article in the Review of Financial Studies, the authors provide an overview of the methods and findings of the first comprehensive study of worldwide hedge fund activism—one that examined the effectiveness of some 1,740 separate “engagements” of public companies by 330 different hedge funds operating in 23 countries in Asia, Europe, and North America during the period 2000‐2010.The study reports, first of all, that the incidence of shareholder activism is greatest in companies and countries with high institutional ownership, particularly U.S. institutions. In virtually all countries, with the possible exception of Japan, large holdings by institutional investors increased the probability that companies would be targeted by activists. Nevertheless, in all countries (except for the United States), foreign institutions—especially U.S. funds investing in non‐U.S. companies—have played a more important role than domestic institutional investors in supporting activism.The authors also report that those engagements that succeeded in producing “outcomes” were accompanied by positive and significant abnormal stock returns, not only upon the announcement of the activist's block purchase, but throughout the entire holding period. “Outcomes” were identified as taking one of four forms: (1) increases in dividends or stock buybacks; (2) replacement of board members; (3) corporate restructurings such as sales or spinoffs of businesses; and (4) takeover (or sale) of the entire company. But if such outcomes were associated with high shareholder returns, in the many cases where there were no such outcomes, the eventual, holding‐period returns to shareholders, even after taking account of the initially positive market reaction to news of the engagement, were indistinguishable from zero.The authors found that activists succeeded in achieving at least one of their proposed outcomes in roughly one out of two (53%) of the 1,740 engagements. But this success rate varied considerably across countries, ranging from a high of 61% for North American companies, to 50% for European companies, but only 18% engagements of Asian companies—with Japan, again, a country of high disclosure returns but unfulfilled expectations and disappointing outcomes. Outcomes also tended to be strongly associated with the roughly 25% of the total engagements that involved two or more activists (referred to as “wolfpacks”) and produced very high returns.
The role of patients in the delivery of safe care in hospital: Study protocol
Authors: Chegini Zahra , Janati Ali , Bababie Javad , Pouraghaei Mahboub 
Published: May 2019

AbstractAimThis paper outlines the protocol for a study aimed at exploring perspectives about the role of patients’ in the delivery of safe care in hospital.DesignQualitative exploratory study.MethodsResearch Ethics Committee approval for this study was obtained in October 2018. The study will be conducted between February–April 2019 with data collected through focus group discussions and semi‐structured interviews and will involve patients and healthcare professionals from hospitals in Tabriz. A descriptive qualitative approach will be adopted, and the data will be managed and analysed using MAXQDA 10 software.DiscussionThe role of patients in furthering their own safety whilst in hospital cannot be underestimated and the results from this study can be used to support the development of practical strategies that address the delivery of safe hospital care and which involve patients and their caregivers.
Targeting EZH2 as a novel therapeutic strategy for sorafenib‐resistant thyroid carcinoma
Authors: Wang Zhengshi , Dai Jiaqi , Yan Jie , Zhang Yun , Yin Zhiqiang 
Published: May 2019

AbstractThyroid carcinoma is the most common endocrine malignancy. Surgery, post‐operative selective iodine‐131 and thyroid hormone suppression were the most common methods for the therapy of thyroid carcinoma. Although most patients with differentiated thyroid carcinoma (DTC) showed positive response for these therapeutic methods, some patients still have to face the radioactive iodine (RAI)‐refractory problems. Sorafenib is an oral multikinase inhibitor for patients with advanced RAI refractory DTC. However, the side effects and drug resistance of sorafenib suggest us to develop novel drugs and strategies for the therapy of thyroid carcinoma. In this study, we firstly found that patients with sorafenib resistance showed no significant change in rapidly accelerated fibrosarcoma and VEGFR expression levels compared with sorafenib sensitive patients. Moreover, a further miRNAs screen by qRT‐PCR indicated that miR‐124‐3p and miR‐506‐3p (miR‐124/506) were remarkably reduced in sorafenib insensitive patients. With a bioinformatics prediction and functional assay validation, we revealed that enhancer of zeste homolog 2 (EZH2) was the direct target for miR‐124/506. Interestingly, we finally proved that the sorafenib resistant cells regained sensitivity for sorafenib by EZH2 intervention with miR‐124/506 overexpression or EZH2 inhibitor treatment in vitro and in vivo, which will lead to the decreased tri‐methylation at lysine 27 of histone H3 (H3K27me3) and increased acetylated lysine 27 of histone H3 (H3K27ac) levels. Therefore, we conclude that the suppression of EZH2 represents a potential target for thyroid carcinoma therapy.
Folic acid deficiency enhanced microglial immune response via the Notch1/nuclear factor kappa B p65 pathway in hippocampus following rat brain I/R injury and BV2 cells
Authors: Cheng Man , Yang Liu , Dong Zhiping , Wang Mengying , Sun Yan , Liu Huan , Wang Xuan , Sai Na , Huang Guowei , Zhang Xumei 
Published: May 2019

AbstractRecent studies revealed that folic acid deficiency (FD) increased the likelihood of stroke and aggravated brain injury after focal cerebral ischaemia. The microglia‐mediated inflammatory response plays a crucial role in the complicated pathologies that lead to ischaemic brain injury. However, whether FD is involved in the activation of microglia and the neuroinflammation after experimental stroke and the underlying mechanism is still unclear. The aim of the present study was to assess whether FD modulates the Notch1/nuclear factor kappa B (NF‐κB) pathway and enhances microglial immune response in a rat middle cerebral artery occlusion‐reperfusion (MCAO) model and oxygen‐glucose deprivation (OGD)‐treated BV‐2 cells. Our results exhibited that FD worsened neuronal cell death and exaggerated microglia activation in the hippocampal CA1, CA3 and Dentate gyrus (DG) subregions after cerebral ischaemia/reperfusion. The hippocampal CA1 region was more sensitive to ischaemic injury and FD treatment. The protein expressions of proinflammatory cytokines such as tumour necrosis factor‐α, interleukin‐1β and interleukin‐6 were also augmented by FD treatment in microglial cells of the post‐ischaemic hippocampus and in vitro OGD‐stressed microglia model. Moreover, FD not only dramatically enhanced the protein expression levels of Notch1 and NF‐κB p65 but also promoted the phosphorylation of pIkBα and the nuclear translocation of NF‐κB p65. Blocking of Notch1 with N‐[N‐(3, 5‐difluorophenacetyl)‐l‐alanyl]‐S‐phenylglycine t‐butyl ester partly attenuated the nuclear translocation of NF‐κB p65 and the protein expression of neuroinflammatory cytokines in FD‐treated hypoxic BV‐2 microglia. These results suggested that Notch1/NF‐κB p65 pathway‐mediated microglial immune response may be a molecular mechanism underlying cerebral ischaemia‐reperfusion injury worsened by FD treatment.