bluuebunny/crossref_metadata_2025_split huggingface dataset:
MiR‐599 regulates LPS‐mediated apoptosis and inflammatory responses through the JAK2/STAT3 signalling pathway via targeting ROCK1 in human umbilical vein endothelial cells
Authors: Wang Jia , Du Aolin , Wang Hexilin , Li Yang 
Published: April 2020

AbstractMicroRNA plays an integral role in the development of atherosclerosis. Our study aimed to investigate the roles of miR‐599 in lipopolysaccharide (LPS)‐induced endothelial damage in human umbilical vein endothelial cells (HUVECs). HUVECs were transfected with a miR‐599 mimic and negative control, and then exposed to LPS. The expression of miR‐599 was detected by quantitative real time‐polymerase chain reaction (RT‐qPCR). Cell viability was analyzed by CCK‐8 assay and trypan blue exclusion assay; the formation of DNA fragments was tested by Cell Death Detection ELISA Plus kit; the incidence of apoptosis was detected by flow cytometry; the expression of p53 and cleaved‐caspase 3 (c‐caspase 3) was evaluated by western blot. Moreover, the mRNA levels and concentrations of tumour necrosis factor (TNF)‐α, interleukin (IL)‐6, ICAM‐1 and VCAM‐1 were assayed by RT‐qPCR and ELISA. The results showed that overexpression of miR‐599 increased cell viability, reduced DNA fragments, the incidence of apoptosis, as well as the protein levels of p53 and c‐caspase 3 in the presence of LPS. TNF‐α, IL‐6, ICAM‐1 and VCAM‐1 mRNA levels and concentrations were also decreased upon miR‐599 upregulation. In addition, the dual luciferase reporter assay demonstrated that ROCK1 is a direct target of miR‐599. MiR‐599 overexpression inhibited ROCK1 expression. Induced expression of ROCK1 reversed the roles of miR‐599 in apoptosis and inflammation. The gain function of miR‐599 function inhibited activation of the JAK2/STAT3 signalling pathway, which was abrogated by overexpression of ROCK1. Taken together, our results indicate that miR‐599 attenuates LPS‐caused cell apoptosis and inflammatory responses through the JAK2/STAT3 signalling pathway via targeting ROCK1.
Characterization of B cell‐mediated PD‐1/PD‐L1 interaction in pancreatic cancer patients
Authors: Tong Da‐Nian , Guan Jiao , Sun Jian‐Hua , Zhao Chong‐Yue , Chen Shi‐Geng , Zhang Zheng‐Yun , Zhou Zun‐Qiang 
Published: April 2020

AbstractPancreatic ductal adenocarcinoma (PDAC) is a common type of pancreatic cancer with one of the worst survival rate of all malignancies. Recent studies have identified that immunosuppressive B cells could employ the PD‐1/PD‐L1 pathway to suppress antitumour T cell responses; hence, we examined the expression and function of PD‐L1 in B cells. We found that the PD‐L1 expression was significantly enriched in tumour‐infiltrating (TI) B cells than in peripheral blood (PB) B cells from the same patients. Additionally, the PB B cells from stage III and stage IV PDAC patients presented significantly higher PD‐L1 than the PB B cells from healthy controls. High PD‐L1 expression in PB B cells could be achieved by stimulation via CpG and less effectively via anti‐BCR plus CD40L, but not by coculture with pancreatic cancer cell lines in vitro. Also, STAT1 and STAT3 inhibition significantly suppressed PD‐L1 upregulation in stimulated B cells. CpG‐stimulated PB B cells could inhibit the IFN‐γ expression and proliferation of CD8 T cells in a PD‐L1‐dependent manner. Also, TI CD8 T cells incubated with whole TI B cells presented significantly lower IFN‐γ expression and lower proliferation, than TI CD8 T cells incubated with PD‐L1+ cell‐depleted TI B cells, suggesting that PD‐L1+ B cells could also suppress CD8 T cells in the tumour. Overall, this study identified that B cells could suppress CD8 T cells via PD‐L1 expression, indicating a novel pathway of immuno‐regulation in pancreatic cancer.
Managing and Measuring Emergency Department Care: Results of the Fourth Emergency Department Benchmarking Definitions Summit
Authors: Yiadom Maame Y. A. B. , Napoli Anthony , Granovsky Michael , Parker Rebecca B. , Pilgrim Randy , Pines Jesse M. , Schuur Jeremiah , Augustine James , Jouriles Nicholas , Welch Shari 
Published: April 2020

AbstractBackgroundA shared language and vocabulary are essential for managing emergency department (ED) operations. This Fourth Emergency Department Benchmarking Alliance (EDBA) Summit brought together experts in the field to review, update, and add to key definitions and metrics of ED operations.ObjectiveSummit objectives were to review and revise existing definitions, define and characterize new practices related to ED operations, and introduce financial and regulatory definitions affecting ED reimbursement.MethodsForty‐six ED operations, data management, and benchmarking experts were invited to participate in the EDBA summit. Before arrival, experts were provided with documents from the three prior summits and assigned to update the terminology. Materials and publications related to standards of ED operations were considered and discussed. Each group submitted a revised set of definitions prior to the summit. Significantly revised, topical, or controversial recommendations were discussed among all summit participants. The goal of the in‐person discussion was to reach consensus on definitions. Work group leaders made changes to reflect the discussion, which was revised with public and stakeholder feedback.ResultsThe entire EDBA dictionary was updated and expanded. This article focuses on an update and discussion of definitions related to specific topics that changed since the last summit, specifically ED intake, boarding, diversion, and observation care. In addition, an extensive new glossary of financial and regulatory terminology germane to the practice of emergency medicine is included.ConclusionsA complete and precise set of operational definitions, time intervals, and utilization measures is necessary for timely and effective ED care. A common language of financial and regulatory definitions that affect ED operations is included for the first time. This article and its companion dictionary should serve as a resource to ED leadership, researchers, informatics and health policy leaders, and regulatory bodies.
Radiography and computed tomography of the heart and lower respiratory tract in toco toucans (Ramphastos toco)
Authors: da Silva Jeana Pereira , Rahal Sheila Canevese , Castiglioni Maria Cristina Reis , Baldissera Gonçalves Raphael Augusto , Doiche Danuta Pulz , Moresco Anneke , Mamprim Maria Jaqueline , Vulcano Luiz Carlos 
Published: April 2020

AbstractThis study aimed to evaluate normal features of the heart and lower respiratory tract in toco toucans by means of radiography and helical computed tomography (CT) scanner. Fifteen healthy adult toco toucans (Ramphastos toco), 10 females and 5 males, average body mass of 650 g were studied. CT examination as well as right lateral and ventrodorsal radiographic examinations of the coelomic cavity were performed under chemical restraint. Heart, lungs, air sacs, trachea and syrinx were analysed. The mean values of heart length, heart width and thoracic cavity in radiographs were, respectively, 23.76 mm, 25.94 mm and 48.87 mm. In both X‐rays and CT scans, the lung parenchyma had honeycomb‐like pattern. The topographic areas of the anterior and posterior air sacs were visualized as dark and air‐filled spaces in X‐rays. On CT evaluation, the air sacs occupied a larger area in the coelomic cavity compared to X‐ray. In the lateral radiographic view, the cervical part of the trachea was positioned more ventrally in the transition from cervical to thoracic regions showing a V‐shaped appearance. In all CT planes was visible division of the trachea into the right and left main bronchi at the level of 3rd thoracic vertebra. The syrinx was difficult to visualize in X‐rays, but on CT it was easily identified in axial slice. In conclusion, the normal features of toco toucan's heart and lower respiratory tract that were determined on X‐rays and CT scans are useful to compare with sick toco toucans, as well as other bird species.
Intrauterine perfusion immunotherapies in recurrent implantation failures: Systematic review
Authors: Cavalcante Marcelo Borges , Cavalcante Candice Torres de Melo Bezerra , Sarno Manoel , Barini Ricardo 
Published: April 2020

AbstractStudies have investigated the gestational outcomes of new immunological therapies in the treatment of patients with recurrent implantation failure (RIF) in assisted reproductive technology (ART). The objective of this article is to assess the current state of evidence available in the literature on intrauterine perfusion immunotherapies in women undergoing ART treatments. By considering the guidelines of Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA), the authors performed systematic review by searching the databases of PubMed/MEDLINE and Scopus using the following key words: “recurrent implantation failure,” “intrauterine infusion,” “Platelet‐Rich Plasma (PRP),” “Peripheral Blood Mononuclear Cells (PBMC),” “Granulocyte Colony‐Stimulating Factor (G‐CSF),” and “Human Chorionic Gonadotropin (hCG).” The authors analyzed the indications and the impact of new immunological therapies with intrauterine infusions on the pregnancy outcomes of patients undergoing ART. PRP, PBMC, G‐CSF, and hCG were the four most used immunological therapies with intrauterine infusion. These new therapies appear to improve the results of ART treatments in cases of RIF. However, the small number of studies does not allow definitive conclusions about the effectiveness of these therapies.
IgE to epitopes of Ara h 2 enhance the diagnostic accuracy of Ara h 2‐specific IgE
Authors: Santos Alexandra F. , Barbosa‐Morais Nuno L. , Hurlburt Barry K. , Ramaswamy Sneha , Hemmings Oliver , Kwok Matthew , O’Rourke Colin , Bahnson Henry T. , Cheng Hsiaopo , James Louisa , Gould Hannah J. , Sutton Brian J. , Maleki Soheila J. , Lack Gideon 
Published: April 2020

AbstractBackgroundUnderstanding the discrepancy between IgE sensitization and allergic reactions to peanut could facilitate diagnosis and lead to novel means of treating peanut allergy.ObjectiveTo identify differences in IgE and IgG4 binding to peanut peptides between peanut‐allergic (PA) and peanut‐sensitized but tolerant (PS) children.MethodsPA (n = 56), PS (n = 42) and nonsensitized nonallergic (NA, n = 10) patients were studied. Synthetic overlapping 15‐mer peptides of peanut allergens (Ara h 1‐11) were spotted onto microarray slides, and patients’ samples were tested for IgE and IgG4 binding using immunofluorescence. IgE and IgG4 levels to selected peptides were quantified using ImmunoCAP. Diagnostic model comparisons were performed using likelihood‐ratio tests between each specified nominal logistic regression models.ResultsSeven peptides on Ara h 1, Ara h 2, and Ara h 3 were bound more by IgE of PA compared to PS patients on the microarray. IgE binding to one peptide on Ara h 5 and IgG4 binding to one Ara h 9 peptide were greater in PS than in PA patients. Using ImmunoCAP, IgE to the Ara h 2 peptides enhanced the diagnostic accuracy of Ara h 2‐specific IgE. Ratios of IgG4/IgE to 4 out of the 7 peptides were higher in PS than in PA subjects.ConclusionsAra h 2 peptide‐specific IgE added diagnostic value to Ara h 2‐specific IgE. Ability of peptide‐specific IgG4 to surmount their IgE counterpart seems to be important in established peanut tolerance.
Controversial aspects of testosterone in the regulation of sexual function in late‐onset hypogonadism
Authors: Maggi Mario , Filippi Sandra , Vignozzi Linda , Rastrelli Giulia 
Published: April 2020

AbstractBackgroundTestosterone (T) plays a pivotal role in coordinating a series of psychological, cognitive and physical events that might (or might not) culminate in male sexual activity. In fact, T deficiency is associated, in a statistically significant way, with several sexual dysfunctions including erectile dysfunction (ED), reduction of spontaneous erection and hypoactive sexual desire (HSD). Although these associations are statistically significant, there is debate if they are also clinically meaningful. In addition, sexual dysfunctions are present also in several metabolic conditions ‐ such as type 2 diabetes mellitus and obesity ‐ that often associate with low T. In particular, this is the case of ED, but not of HSD, that, therefore, should be considered a more genuine correlate of T deficiency in adulthood and aging (late‐onset hypogonadism, LOH).ObjectivesThe aim of this review is to scrutinize evidence from our and other studies on sexual effects of T replacement therapy (TRT) in LOH.Materials and methodsWe will use preclinical and clinical data coming from our and other laboratories and meta‐analyses.ResultsIntervention studies in clinical trials involving subjects with LOH, and their meta‐analyses, indicate that TRT is able to ameliorate HSD, spontaneous erection and ED. However, the relative improvement of ED by TRT is marginal [2‐3 points of International Index of Erectile Function‐erectile function domain (IIEF‐EFD)] and significantly smoothed in subjects with the aforementioned metabolic conditions. In LOH, positive effects of TRT on other domains of sexual activity, such as orgasm and sexual satisfaction, are also apparent in the different meta‐analyses.Discussion and conclusionsHence, TRT is a reasonable treatment for restoring sexual drive in LOH, with some additional positive effects also on erection (spontaneous and sexual‐related) and on orgasm. In contrast, preclinical and clinical studies indicate that T administration to eugonadal subjects does not improve male sexual activity.
Retinal oximetry in glaucoma: investigations and findings reviewed
Authors: Shughoury Aumer , Mathew Sunu , Arciero Julia , Wurster Patrick , Adjei Susuana , Ciulla Thomas , Siesky Brent , Harris Alon 
Published: April 2020

AbstractAbnormalities of the retinal blood supply have been widely implicated in primary open‐angle glaucoma (POAG). Impaired blood supply to the retina and optic nerve head (ONH) may be a primary pathophysiologic mechanism contributing to POAG (‘vascular hypothesis’). However, the decreased metabolic activity of atrophic tissue is itself known to induce both vascular changes and decreased blood flow due to reduced oxygen demand. Therefore, primary nonvascular factors could potentially induce glaucomatous atrophy, with subsequent secondary vascular pathology (‘mechanical hypothesis’). Retinal oximetry holds great promise in the investigation of glaucoma pathogenesis, as it can provide useful data on retinal metabolic oxygen demand, especially when combined with measurements of retinal blood flow. This review surveys the research on retinal metabolism in POAG using spectroscopic retinal oximetry. The use of mathematical models in combination with oximetric data to investigate the role of retinal metabolism and oxygen supply in POAG is also discussed.
Interactions between ocular and systemic disease using national register‐based data in the Danish Excellence Centre in Ophthalmic Epidemiology (DECODE‐EYE): study perspective
Authors: Grauslund Jakob , Stokholm Lonny , Ohm Kyvik Kirsten , Dornonville de la Cour Morten , Kessel Line , Hass Rubin Katrine 
Published: April 2020

AbstractPurposeThe Danish Excellence Centre in Ophthalmic Epidemiology (DECODE‐EYE) is a national research collaboration formed in order to study the real‐life interaction between ocular and systemic disease based on the entire Danish population. Here, we aim to describe the study design and the methodology, which will be used.MethodsWe will extract data from various healthcare registers and databases including the Danish Civil Registration System (unique personal identifier), the Danish National Patient Register (inpatient and outpatient visits), the Danish National Prescription Registry (redeemed prescription drugs), the National Health Service Register (data on health services in primary health care), the Danish Register of Cause of Death (data on cause of death), Statistics Denmark (demographic and socioeconomic data), the Danish Registry of Diabetic Retinopathy (level of diabetic retinopathy (DR) in diabetes patients) and the database of the Danish Association of the Blind (date and cause of blindness). Relevant registers will be linked by the unique personal identifier, and associations will be examined cross‐sectional and/or longitudinally, in principle in 1:5 age‐ and gender‐matched case–control cohort studies.ConclusionDenmark has a strong tradition in register‐based healthcare research, given a high number of validated national registers and databases. DECODE‐EYE will provide Danish, large‐scale data on associations between ocular and systemic disease.With a target population of 5.8 million individuals, twelve separate studies (Protocols A–L) have initially been designed to be studied in the upcoming years. These will provide novel data on interactions between systemic disease and relevant ophthalmological end‐points like blindness, DR, glaucoma, corneal disease, retinal vascular disease, cataract and intravitreal angiostatic treatment.
Propofol in neonates causes a dose‐dependent profound and protracted decrease in blood pressure
Authors: de Kort Ellen H. M. , Twisk Jos W. R. , van t Verlaat Ellen P. G. , Reiss Irwin K. M. , Simons Sinno H. P. , van Weissenbruch Mirjam M. 
Published: April 2020

AbstractAimTo analyse the effects of different propofol starting doses as premedication for endotracheal intubation on blood pressure in neonates.MethodsNeonates who received propofol starting doses of 1.0 mg/kg (n = 30), 1.5 mg/kg (n = 23) or 2.0 mg/kg (n = 26) as part of a previously published dose‐finding study were included in this analysis. Blood pressure in the 3 dosing groups was analysed in the first 60 minutes after start of propofol.ResultsBlood pressure declined after the start of propofol in all 3 dosing groups and was not restored 60 minutes after the start of propofol. The decline in blood pressure was highest in the 2.0 mg/kg dosing group. Blood pressure decline was mainly dependent on the initial propofol starting dose rather than the cumulative propofol dose.ConclusionPropofol causes a dose‐dependent profound and prolonged decrease in blood pressure. The use of propofol should be carefully considered. When using propofol, starting with a low dose and titrating according to sedative effect seems the safest strategy.
Death‐scene investigations contribute to legal protection in unexpected child deaths in Norway
Authors: Bøylestad Lillian , Stray‐Pedersen Arne , Vege Åshild , Osberg Silje , Rognum Torleiv 
Published: April 2020

AbstractAimThis study reviewed cases of sudden unexpected child deaths in Norway to determine the significance of death‐scene investigations (DSIs) in establishing cause and manner of death, and thereby it is relevance to legal protection.MethodsData from forensic autopsy reports and DSIs were collected and analysed for cases of unexpected deaths in children below 4 years of age in Norway during 2010‐2016.ResultsOut of 141 cases, the death scene was investigated as a voluntary procedure in 75 cases and by the police in 41 cases. The cause of death remained unexplained in 81/141 (57%) of the cases, of which 46/141 (33%) met the criteria for sudden infant death syndrome (SIDS) or sudden unexplained death in early childhood (SUDC). The manner of death was determined in 102/141 (72%). Voluntary DSI increased the ability to rule out accidental suffocation, facilitated evaluations of environmental risk factors and enabled detection of possible neglect.ConclusionDeath‐scene investigations illuminate uncertainty about the cause of death, especially in grey‐area cases where accidental suffocation, neglect or abuse is suspected. Knowledge about the course of events and the cause of death enhances both the child's and the caregiver's legal protection. Death‐scene investigations should therefore be mandatory.
Absorption, distribution, metabolism and excretion of molidustat in healthy participants
Authors: Lentini Silvia , van der Mey Dorina , Kern Armin , Thuss Uwe , Kaiser Andreas , Matsuno Kumi , Gerisch Michael 
Published: April 2020

AbstractThe absorption, distribution, metabolism and excretion of molidustat were investigated in healthy male participants. In study 1, a mass balance study, radiolabelled molidustat 25 mg (3.57 MBq) was administered as an oral solution (n = 4). Following rapid absorption, molidustat‐related radioactivity was predominantly distributed in plasma rather than in red blood cells. The total recovery of the administered radioactivity was 97.0%, which was mainly excreted renally (90.7%). Metabolite M‐1, produced by N‐glucuronidation, was the dominant component in plasma (80.2% of the area under the concentration‐time curve for total radioactivity) and was primarily excreted via urine (~85% of dose). Only minor amounts of unchanged molidustat were excreted in urine (~4%) and faeces (~6%). Study 2 investigated the absolute bioavailability and pharmacodynamics of molidustat (part 1, n = 12; part 2, n = 16). Orally administered molidustat immediate release tablets had an absolute bioavailability of 59%. Following intravenous administration (1, 5 and 25 mg), total body clearance of molidustat was 28.7‐34.5 L/h and volume of distribution at steady state was 39.3‐50.0 L. All doses of molidustat transiently elevated endogenous erythropoietin levels, irrespective of the route of administration. Molidustat was considered safe and well tolerated at the administered doses.
Coordinating learning analytics policymaking and implementation at scale
Authors: Broos Tom , Hilliger Isabel , Pérez-Sanagustín Mar , Htun Nyi‐Nyi , Millecamp Martijn , Pesántez-Cabrera Paola , Solano‐Quinde Lizandro , Siguenza‐Guzman Lorena , Zuñiga‐Prieto Miguel , Verbert Katrien , De Laet Tinne 
Published: April 2020

AbstractMany Latin‐American institutions recognise the potential of learning analytics (LA). However, the number of actual LA implementations at scale remains limited, notwithstanding considerable effort made to formulate guidelines and frameworks to support the LA policy development. Guidance on how to coordinate the interaction between the LA policymaking and implementation is mostly missing, leaving a difficult challenge up to practitioners. In this study we propose a coordination model to support future LA initiatives at scale. We explore the problem by comparing two cases in Belgium and Ecuador. Following up we use the LA implementation timeline as a driver for planning the interaction between the policymaking and implementation. We continue by testing an application of the model with LA experts predominantly from Latin‐American institutions, asking them to map low‐level items of the SHEILA policy framework to four implementation phases. The results of this mapping support that LA policy building can be spread over time, that it can coincide with LA implementation at scale, and that both efforts can be coordinated. It is hoped that this study will provide additional guidance for future Latin‐American and other LA initiatives.