bluuebunny/crossref_metadata_2025_split huggingface dataset:
Steroids and nonsteroidal anti‐inflammatory drugs in the postoperative regime after trabeculectomy – which provides the better outcome? A systematic review and meta‐analysis
Authors: Almatlouh Amir , Bach‐Holm Daniella , Kessel Line 
Published: September 2018

AbstractSurgical outcome after trabeculectomy depends on maintaining a functional bleb which requires a delicate balance between incomplete wound healing to prevent fibrosis and enough wound healing to prevent hyperfiltration. Thus, controlling the inflammatory response is essential. We conducted a systematic review and meta‐analysis to compare the effectiveness of different formulations of steroids (topical, systemic and depot) and nonsteroidal anti‐inflammatory drugs (NSAIDs) in achieving long‐term pressure control with fewer antiglaucomatous medications, preserving visual acuity and visual fields while considering surgical and postoperative complications. We used the PubMed, EMBASE and Cochrane Libraries to identify randomized controlled trials (RCTs) comparing the effect of different formulations of steroids (topical, systemic or depot) to NSAIDs. Data on prespecified outcomes from eligible references were entered into a meta‐analysis using the Review Manager 5.3 program. We identified seven RCTs with a total of 342 included patients. Topical steroids were superior to placebo in controlling intraocular pressure (IOP) and reducing the risk of complications. Supplementing topical steroids with a perioperative steroid depot (subtenon or intracamerally) or systemic steroids in the early postoperative period did not provide better outcome or a change in the risk of complications. Addition of topical NSAIDs to topical steroids in patients undergoing trabeculectomy did not change the outcome or risk profile. For patients undergoing phacotrabeculectomy and topical NSAID, there was a nonsignificant trend towards better intermediate IOP control and a reduced need for antiglaucomatous medications compared to topical steroids but there was no difference in effect for patients undergoing trabeculectomy. In conclusion, there is a low level of evidence to support the clinician in deciding which postoperative regime provides a more favourable outcome because of inconsistency in the reported outcomes between studies and a low number of patients for each comparable intervention and outcome. It does seem that topical steroids are better than no anti‐inflammatory treatment after glaucoma surgery, but further research is recommended.
High‐versus low‐dose caffeine in preterm infants: a systematic review and meta‐analysis
Authors: Brattström Petter , Russo Chiara , Ley David , Bruschettini Matteo 
Published: September 2018

AbstractAimThough caffeine is a consolidated treatment in preterm infants, the efficacy and safety of a higher dose have not been systematically appraised.MethodsA systematic review was conducted to compare high (loading dose >20 mg/kg and maintenance >10 mg/kg/day) versus low dose of caffeine. MEDLINE, EMBASE, Central and conference proceedings for randomised controlled trials (RCTs) and quasi‐RCTs were searched. Two authors independently screened the records, extracted the data and assessed the risk of bias.ResultsAs only six RCTs enrolling a total of 816 preterm infants were included, the required information size was not reached. The loading and maintenance doses varied between 20 and 80 mg/kg/day and 3 and 20 mg/kg/day, respectively. The use of high dose had no impact on mortality (RR: 0.85; 95% CI: 0.53–1.38; RCTs = 4). However, it resulted in fewer cases of extubation failure, apnoeas and bronchopulmonary dysplasia (RR: 0.76; 95% CI: 0.60–0.96; studies = 4) and shorter duration of mechanical ventilation. The quality of the evidence was low due to imprecision of the estimates.ConclusionDue to imprecision, it is not possible to determine whether high‐dose caffeine is more effective and safe than a low dose. High dose might improve short‐term respiratory function and reduce bronchopulmonary dysplasia.
Effects of physical exercise during pregnancy on maternal and infant outcomes in overweight and obese pregnant women: A meta‐analysis
Authors: Du Mei‐Chen , Ouyang Yan‐Qiong , Nie Xiao‐Fei , Huang Yi , Redding Sharon R. 
Published: September 2018

AbstractBackgroundOverweight and obesity are related to maternal and infant physical health, such as gestational diabetes, preeclampsia, and macrosomia. The purpose of this meta‐analysis was to assess the effect of physical exercise on maternal and infant outcomes in overweight and obese pregnant women.MethodsTwo researchers independently searched Cochrane Library, Embase, PubMed, Web of Science, and ClinicalTrials.gov. for English‐language articles based on randomized controlled trials examining physical exercise in overweight and obese pregnant women and its effect on maternal and infant outcomes. Primary outcomes were gestational weight gain and a relative risk of gestational diabetes. Secondary outcomes were gestational hypertension, preeclampsia, cesarean delivery, birthweight, large for gestational age, small for gestational age, macrosomia, and preterm birth. Risk bias was evaluated by Cochrane Collaboration's tool. The results of integration were reported as relative risks (RR), mean difference, or standard mean difference with 95% confidence intervals (CI). This meta‐analysis was registered on PROSPERO on November 18, 2017, with registration number CRD42017081565.ResultsThirteen studies involving 1439 participants were included. Physical exercise reduced gestational weight gain (mean difference = −1.14 kg, 95% CI = [−1.67 to −0.62], P < 0.0001) and the risk of gestational diabetes (RR = 0.71, 95% CI = [0.57‐0.89], P = 0.004) in overweight and obese pregnant women. There were no significant differences in other outcomes such as gestational hypertension, preeclampsia, cesarean delivery, birthweight, large for gestational age, small for gestational age, macrosomia, and preterm birth.ConclusionsPrenatal exercise interventions reduced gestational weight gain and the risk of gestational diabetes for overweight and obese pregnant women, which reinforced the benefits of exercise during pregnancy. However, no evidence was found with respect to benefits and/or harm for infants. Consideration should be taken when interpreting these findings as a result of the relative small sample size in this meta‐analysis. Further larger well‐designed randomized trials may be helpful to assess the short‐term and long‐term effects of prenatal exercise on maternal and infant outcomes.
Exploring TPACK among pre‐service teachers in Australia and Israel
Authors: Redmond Petrea , Peled Yehuda 
Published: September 2018

AbstractThe ubiquitous nature of technology in the world has not yet translated into the ubiquitous use of technology to transform learning and teaching. Teachers lack the confidence and competence to integrate technology across a broad range of tools within a range of contexts. Technological pedagogical content knowledge (TPACK) has become a common framework to explore technology within teaching and teacher education. However, little research exists to explore the similarities and differences of TPACK between different teacher education programmes, within different countries or even different disciplines, especially in a secondary context. Using a self‐report online survey, this study sought to compare and contrast TPACK results from pre‐service teachers studying in secondary teacher education programmes in Australia and Israel. Findings suggest that TPACK is higher in Australia, and in both countries for those students who were aged over 26. There were no significant differences between gender and disciplines reported. The paper also discusses broad‐scale implications for the future of research in TPACK.
Immediate versus delayed exercise in men initiating androgen deprivation: effects on bone density and soft tissue composition
Authors: Taaffe Dennis R. , Galvão Daniel A. , Spry Nigel , Joseph David , Chambers Suzanne K. , Gardiner Robert A. , Hayne Dickon , Cormie Prue , Shum David H.K. , Newton Robert U. 
Published: September 2018

ObjectivesTo examine whether it is more efficacious to commence exercise medicine in men with prostate cancer at the onset of androgen‐deprivation therapy (ADT) rather than later on during treatment to preserve bone and soft‐tissue composition, as ADT results in adverse effects including: reduced bone mineral density (BMD), loss of muscle mass, and increased fat mass (FM).Patients and methodsIn all, 104 patients with prostate cancer, aged 48–84 years initiating ADT, were randomised to immediate exercise (IMEX, n = 54) or delayed exercise (DEL, n = 50) conditions. The former consisted of 6 months of supervised resistance/aerobic/impact exercise and the latter comprised 6 months of usual care followed by 6 months of the identical exercise programme. Regional and whole body BMD, lean mass (LM), whole body FM and trunk FM, and appendicular skeletal muscle (ASM) were assessed by dual X‐ray absorptiometry, and muscle density by peripheral quantitative computed tomography at baseline, and at 6 and 12 months.ResultsThere was a significant time effect (P < 0.001) for whole body, spine and hip BMD with a progressive loss in the IMEX and DEL groups, although lumbar spine BMD was largely preserved in the IMEX group at 6 months compared with the DEL group (−0.4% vs −1.6%). LM, ASM, and muscle density were preserved in the IMEX group at 6 months, declined in the DEL group at 6 months (−1.4% to −2.5%) and then recovered at 12 months after training. FM and trunk FM increased (P < 0.001) over the 12‐month period in the IMEX (7.8% and 4.5%, respectively) and DEL groups (6.5% and 4.3%, respectively).ConclusionsCommencing exercise at the onset of ADT preserves lumbar spine BMD, muscle mass, and muscle density. To avoid treatment‐related adverse musculoskeletal effects, exercise medicine should be prescribed and commenced at the onset of ADT.
Prospective comparison of a fast 1.5‐T biparametric with the 3.0‐T multiparametric ESUR magnetic resonance imaging protocol as a triage test for men at risk of prostate cancer
Authors: Van Nieuwenhove Sandy , Saussez Thibaud Pierre , Thiry Sarah , Trefois Pierre , Annet Laurence , Michoux Nicolas , Lecouvet Frédéric , Tombal Bertrand 
Published: September 2018

ObjectiveTo compare prospectively the diagnostic performance of a biparametric (T2‐weighted imaging [T2WI] and diffusion‐weighted imaging [DWI]) 1.5‐T fast magnetic resonance imaging (fMRI) protocol with the standard 3.0‐T multiparametric MRI (mpMRI) protocol of the European Society of Urological Imaging (ESUR) in men referred for a prostate biopsy.Patients and MethodsNinety patients with a prostate cancer (PCa) risk of ≥10% according to the SWOP calculator 4 underwent first fMRI and then the reference mpMRI. Patients with Prostate Imaging Reporting and Data System (PI‐RADS) v.2 lesions ≥3/5 on the mpMRI were scheduled for MRI/ultrasonography (US) fusion‐guided prostate biopsy. Performance of fMRI was assessed using receiver‐operating characteristic curve analysis and mpMRI as reference. Calculation of inter‐technique agreement on PI‐RADS v.2 score by Cohen's κ.ResultsThe diagnostic accuracy of fMRI shown by the lesion‐based analysis was excellent: area under the curve (AUC) 0.961 (P < 0.001), sensitivity 95%, specificity 97%, positive predictive value (PPV) 99%, negative predictive value (NPV) 89%. The patient‐based analysis showed an AUC for fMRI of 0.975 (P < 0.001), a sensitivity of 98%, a specificity of 97%, a PPV of 98% and an NPV of 97%. Agreement on the PI‐RADS score between both protocols was found to be good (κ = 0.78 [0.57; 0.99]); fMRI missing PI‐RADS 4 lesions in three patients. Biopsy results showed no cancer in two patients (two cores per nodule) and Gleason 6 cancer in one patient. There was only one false‐positive fMRI, with a PI‐RADS score of 4, whose biopsy was negative.ConclusionIn the triage of men with a high risk of PCa for prostate biopsy, an f MRI protocol (1.5‐T magnet, T2WI + DWI, <15 min) may safely replace the traditional ESUR 3.0‐T mpMRI protocol, saving time and contrast injection.
Applications of mechanistic modelling to clinical and experimental immunology: an emerging technology to accelerate immunotherapeutic discovery and development
Authors: Brown L V , Gaffney E A , Wagg J , Coles M C 
Published: September 2018

Summary
The application of in silico modelling is beginning to emerge as a key methodology to advance our understanding of mechanisms of disease pathophysiology and related drug action, and in the design of experimental medicine and clinical studies. From this perspective, we will present a non-technical discussion of a small number of recent and historical applications of mathematical, statistical and computational modelling to clinical and experimental immunology. We focus specifically upon mechanistic questions relating to human viral infection, tumour growth and metastasis and T cell activation. These exemplar applications highlight the potential of this approach to impact upon human immunology informed by ever-expanding experimental, clinical and ‘omics’ data. Despite the capacity of mechanistic modelling to accelerate therapeutic discovery and development and to de-risk clinical trial design, it is not widely utilised across the field. We outline ongoing challenges facing the integration of mechanistic modelling with experimental and clinical immunology, and suggest how these may be overcome. Advances in key technologies, including multiscale modelling, machine learning and the wealth of ‘omics’ data sets, coupled with advancements in computational capacity, are providing the basis for mechanistic modelling to impact on immunotherapeutic discovery and development during the next decade.
Blood immune cell biomarkers in lung cancer
Authors: Riemann D , Cwikowski M , Turzer S , Giese T , Grallert M , Schütte W , Seliger B 
Published: September 2018

Summary
Characterization of host immune cell parameters prior to treatment is expected to identify biomarkers predictive of clinical outcome as well as to elucidate why some patients fail to respond to immunotherapy. We monitored blood immune cells from 58 patients with non-small- cell lung cancer (NSCLC) undergoing surgery of the primary tumor and from 50 age-matched healthy volunteers. Complete leukocyte blood count, the number of circulating dendritic cells (DC), HLA-DRlow monocytes and several lymphocytic subpopulations were determined by eight-color flow cytometry. Furthermore, the prognostic value of the immune cell parameters investigated was evaluated by patients’ survival analysis. Compared to the control group, blood of NSCLC patients contained more neutrophils resulting in a higher neutrophil-to-lymphocyte ratio (NLR), but a lower number of blood DC, in particular of plasmacytoid DC (pDC), natural killer (NK) cells and naive CD4+ and CD8+ T cells. Furthermore, a higher frequency of CD4+ regulatory T cells (Treg) and HLA-DRlow monocytes was detected, and smoking had a significant impact on these values. HLA-DRlow monocytes were positively correlated to the number of neutrophils, monocytes and NLR, but negatively associated with the number of pDC and naive CD4+ T cells. The frequency of Treg, HLA-DRlow monocytes and naive CD4+ and CD8+ T cells as well as the ratios of CD4/HLA-DRlow monocytes and HLA-DRlow monocytes/pDC correlated with patient’s overall survival. Next to Treg, HLA-DRlow monocytes and naive T cells represent prognostic markers for NSCLC patients and might be useful for monitoring of patients’ responses to immunotherapies in future studies.
Discovery of a small molecule modulator of the Kv1.1/Kvβ1 channel complex that reduces neuronal excitability and in vitro epileptiform activity
Authors: Niespodziany Isabelle , Mullier Brice , André Véronique Marie , Ghisdal Philippe , Jnoff Eric , Moreno‐Delgado David , Swinnen Dominique , Sands Zara , Wood Martyn , Wolff Christian 
Published: September 2018

SummaryAimsKv1.1 (KCNA1) channels contribute to the control of neuronal excitability and have been associated with epilepsy. Kv1.1 channels can associate with the cytoplasmic Kvβ1 subunit resulting in rapid inactivating A‐type currents. We hypothesized that removal of channel inactivation, by modulating Kv1.1/Kvβ1 interaction with a small molecule, would lead to decreased neuronal excitability and anticonvulsant activity.MethodsWe applied high‐throughput screening to identify ligands able to modulate the Kv1.1‐T1 domain/Kvβ1 protein complex. We then selected a compound that was characterized on recombinant Kv1.1/Kvβ1 channels by electrophysiology and further evaluated on sustained neuronal firing and on in vitro epileptiform activity using a high K+‐low Ca2+ model in hippocampal slices.ResultsWe identified a novel compound able to modulate the interaction of the Kv1.1/Kvβ1 complex and that produced a functional inhibition of Kv1.1/Kvβ1 channel inactivation. We demonstrated that this compound reduced the sustained repetitive firing in hippocampal neurons and was able to abolish the development of in vitro epileptiform activity.ConclusionsThis study describes a rational drug discovery approach for the identification of novel ligands that inhibit Kv1.1 channel inactivation and provides pharmacological evidence that such a mechanism translates into physiological effects by reducing in vitro epileptiform activity.
The Effect of Social Network Size on Hashtag Adoption on Twitter
Authors: Monster Iris , Lev‐Ari Shiri 
Published: September 2018

AbstractPropagation of novel linguistic terms is an important aspect of language use and language change. Here, we test how social network size influences people's likelihood of adopting novel labels by examining hashtag use on Twitter. Specifically, we test whether following fewer Twitter users leads to more varied and malleable hashtag use on Twitter, because each followed user is ascribed greater weight and thus exerts greater influence on the following user. Focusing on Dutch users tweeting about the terrorist attack in Brussels in 2016, we show that people who follow fewer other users use a larger number of unique hashtags to refer to the event, reflecting greater malleability and variability in use. These results have implications for theories of language learning, language use, and language change.
Hepatic artery stenosis after liver transplant: Donation after cardiac death donor vs donation after brain death donor grafts
Authors: Lee David D. , Paz‐Fumagalli Ricardo , Croome Kristopher P. , Paz Diego , Wright Lauren , Nguyen Justin H. , Taner C. Burcin 
Published: September 2018

AbstractBackgroundHepatic artery stenosis (HAS) after liver transplant (LT) is a source of significant morbidity. Some reports have suggested higher arterial complications in patients who receive donation after cardiac death (DCD) livers.MethodsA total of 2860 consecutive LT were reviewed from a prospectively collected database. All angiograms performed in LT recipients were reviewed and primary patency rates determined by need for further intervention or graft loss due to HAT.ResultsHepatic artery stenosis was seen in 4.6% of DCD and donation after brain death (DBD) recipients. Recipient male gender, age at transplant, complex donor hepatic artery anatomy, and prolonged operative time were all associated with HAS, but not DCD status. While HAS in recipients of DCD grafts required more stents (1.7% vs 0.6%, P = 0.04) and had worse primary patency rates (logrank, P = 0.02), outcomes as defined by HAT, patient and graft survival were not significantly different between the recipients of DCD or DBD grafts.ConclusionWe observed no significant difference in the incidence of hepatic artery complications, patient survival, or graft survival in recipients of DCD or DBD grafts. However, HAS in DCD recipients had worse primary patency and a higher need for stent placement.
NYX‐2925, A Novel N‐methyl‐D‐aspartate Receptor Modulator: A First‐in‐Human, Randomized, Double‐blind Study of Safety and Pharmacokinetics in Adults
Authors: Houck David R. , Sindelar Laurel , Sanabria Carlos R. , Stanworth Stephanie H. , Krueger Maggie , Suh Mary , Madsen Torsten M. 
Published: September 2018

NYX‐2925, a new chemical entity, acts as a co‐agonist to glutamate at the N‐methyl‐D‐aspartate receptor (NMDAR). At low concentrations of endogenous agonists (glycine/D‐serine), NYX‐2925 partially activates NMDARs, modulating neural pathways relevant for chronic pain. NYX‐2925 is being developed for the treatment of chronic pain conditions, including painful diabetic peripheral neuropathy and fibromyalgia. In this first‐in‐human, phase I, single‐ascending dose (50–1,200 mg) and multiple‐ascending dose (150–900 mg) study, the safety, tolerability, and pharmacokinetics (PKs) of NYX‐2925 were evaluated in 84 healthy adult volunteers. No safety concerns emerged, including no dissociative side effects. NYX‐2925 exhibited dose‐proportional PKs and minimal accumulation following once‐daily dosing for 7 days. Cerebrospinal fluid (CSF) measurements confirmed that NYX‐2925 crosses the blood brain barrier, with maximum CSF concentrations approximating 6–9% of maximum plasma concentrations at the same dose level. NYX‐2925 was safe and well‐tolerated in healthy volunteers, and the study results support the continued clinical development for chronic pain conditions.
Reversible cerebral vasoconstriction syndrome in paediatric patients with systemic lupus erythematosus: implications for management
Authors: Durrleman Chloé , Naggara Olivier , Grevent David , Belot Alexandre , Desgranges Marie , Boyer Olivia , Chabrier Stéphane , Bader‐Meunier Brigitte , Kossorotoff Manoelle 
Published: September 2018

Microvascular brain injury is well recognized in neuropsychiatric systemic lupus erythematosus (SLE), but cerebral large artery involvement is being debated. Three females with SLE, aged 9 to 14 years, had immunosuppressive treatment intensification because of lupus nephritis. Within the following days or weeks, they presented with intense cephalalgia – isolated or associated with neurological symptoms – and no or mild hypertension. Magnetic resonance angiography showed multiple stenoses within the circle of Willis. One patient had subsequent small subcortical cerebral infarction. Two patients were treated for neuropsychiatric SLE; one patient was treated for reversible cerebral vasoconstriction syndrome (RCVS). Angiography normalized within a few weeks in all three patients. Retrospectively, clinical and radiological features suggest that RCVS was the most likely diagnosis in all patients. Multidisciplinary analysis of clinical and angiographic features is recommended, as RCVS is rare in children and its recognition may help to adjust treatment.What this paper adds

Reversible vasoconstriction syndrome was observed in paediatric systemic lupus erythematosus.

Thorough imaging analysis was necessary to address this diagnosis in paediatric patients.