bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating methodological quality of Prognostic models Including Patient-reported HeAlth outcomes iN oncologY (EPIPHANY): a systematic review protocol
Authors: Deliu Nina , Cottone Francesco , Collins Gary S , Anota Amélie , Efficace Fabio 
Published: October 2018

IntroductionWhile there is mounting evidence of the independent prognostic value of patient-reported outcomes (PROs) for overall survival (OS) in patients with cancer, it is known that the conduct of these studies may hold a number of methodological challenges. The aim of this systematic review is to evaluate the quality of published studies in this research area, in order to identify methodological and statistical issues deserving special attention and to also possibly provide evidence-based recommendations.Methods and analysisAn electronic search strategy will be performed in PubMed to identify studies developing or validating a prognostic model which includes PROs as predictors. Two reviewers will independently be involved in data collection using a predefined and standardised data extraction form including information related to study characteristics, PROs measures used and multivariable prognostic models. Studies selection will be reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, with data extraction form using fields from the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS) checklist for multivariable models. Methodological quality assessment will also be performed and will be based on prespecified domains of the CHARMS checklist. As a substantial heterogeneity of included studies is expected, a narrative evidence synthesis will also be provided.Ethics and disseminationGiven that this systematic review will use only published data, ethical permissions will not be required. Findings from this review will be published in peer-reviewed scientific journals and presented at major international conferences. We anticipate that this review will contribute to identify key areas of improvement for conducting and reporting prognostic factor analyses with PROs in oncology and will lay the groundwork for developing future evidence-based recommendations in this area of research.Prospero registration numberCRD42018099160.
Comparing the effectiveness of a hybrid simulation/lecture session versus simulation alone in teaching crew resource management (CRM) skills: a randomised controlled trial
Authors: Mempin Roberto L , Simon Wendy M , Napolitano Jason D , Brook Rachel P , Hall Owen L , Vangala Sitaram , Lee Edward S 
Published: October 2018

IntroductionVarious methods have been used to teach crew resource management (CRM) skills, including high-fidelity patient simulation. It is unclear whether a didactic lecture added on to a simulation-based curriculum can augment a learner’s education.MethodsUsing an already existing simulation-based curriculum for interdisciplinary teams composed of both residents and nurses, teams were randomised to an intervention or control arm. The intervention arm had a 10 min didactic lecture after the first of three simulation scenarios, while the control arm did all three simulation scenarios without any didactic component. The CRM skills of teams were then scored, and improvement was compared between the two arms using general estimating equations.ResultsThe differences in mean teamwork scores between the intervention and control arms in scenarios 2 and 3 were not statistically significant. Mean scores in the intervention arm were lower than in the control arm (−0.57, p=0.78 for scenario 2; −3.12, p=0.13 for scenario 3), and the increase in scores from scenario 2 to 3 was lower in the intervention arm than in the control arm (difference in differences: −2.55, p=0.73).ConclusionsAdding a didactic lecture to a simulation-based curriculum geared at teaching CRM skills to interdisciplinary teams did not lead to significantly improved teamwork.
Sleep in youth with autism spectrum disorders: systematic review and meta-analysis of subjective and objective studies
Authors: Díaz-Román Amparo , Zhang Junhua , Delorme Richard , Beggiato Anita , Cortese Samuele 
Published: October 2018

BackgroundSleep problems are common and impairing in individuals with autism spectrum disorders (ASD). Evidence synthesis including both subjective (ie, measured with questionnaires) and objective (ie, quantified with neurophysiological tools) sleep alterations in youth with ASD is currently lacking.ObjectiveWe conducted a systematic review and meta-analysis of subjective and objective studies sleep studies in youth with ASD.MethodsWe searched the following electronic databases with no language, date or type of document restriction up to 23 May 2018: PubMed, PsycInfo, Embase+Embase Classic, Ovid Medline and Web of Knowledge. Random-effects models were used. Heterogeneity was assessed with Cochran’s Q and I2statistics. Publication (small studies) bias was assessed with final plots and the Egger’s test. Study quality was evaluated with the Newcastle Ottawa Scale. Analyses were conducted usingReview ManagerandComprehensive Meta-Analysis.FindingsFrom a pool of 3359 non-duplicate potentially relevant references, 47 datasets were included in the meta-analyses. Subjective and objective sleep outcome measures were extracted from 37 and 15 studies, respectively. Only five studies were based on comorbidity free, medication-naïve participants. Compared with typically developing controls, youth with ASD significantly differed in 10/14 subjective parameters and in 7/14 objective sleep parameters. The average quality score in the Newcastle-Ottawa Scale was 5.9/9.Discussion and clinical implicationsA number of subjective and, to a less extent, objective sleep alterations might characterise youth with ASD, but future studies should assess the impact of pharmacological treatment and psychiatric comorbidities.
Spectral expansion of random sum complexes
Authors: Beit-Aharon Orr , Meshulam Roy 
Published: October 2018

Let [Formula: see text] be a finite abelian group of order [Formula: see text] and let [Formula: see text] denote the [Formula: see text]-simplex on the vertex set [Formula: see text]. The sum complex [Formula: see text] associated to a subset [Formula: see text] and [Formula: see text], is the [Formula: see text]-dimensional simplicial complex obtained by taking the full [Formula: see text]-skeleton of [Formula: see text] together with all [Formula: see text]-subsets [Formula: see text] that satisfy [Formula: see text]. Let [Formula: see text] denote the space of complex-valued [Formula: see text]-cochains of [Formula: see text]. Let [Formula: see text] denote the reduced [Formula: see text]th Laplacian of [Formula: see text], and let [Formula: see text] be the minimal eigenvalue of [Formula: see text]. It is shown that if [Formula: see text] and [Formula: see text] are fixed, and [Formula: see text] is a random subset of [Formula: see text] of size [Formula: see text], then [Formula: see text]
Temozolomide Induces Senescence and Repression of DNA Repair Pathways in Glioblastoma Cells via Activation of ATR–CHK1, p21, and NF-κB
Authors: Aasland Dorthe , Götzinger Laura , Hauck Laura , Berte Nancy , Meyer Jessica , Effenberger Melanie , Schneider Simon , Reuber Emelie E. , Roos Wynand P. , Tomicic Maja T. , Kaina Bernd , Christmann Markus 
Published: October 2018

Abstract

The DNA-methylating drug temozolomide, which induces cell death through apoptosis, is used for the treatment of malignant glioma. Here, we investigate the mechanisms underlying the ability of temozolomide to induce senescence in glioblastoma cells. Temozolomide-induced senescence was triggered by the specific DNA lesion O6-methylguanine (O6MeG) and characterized by arrest of cells in the G2–M phase. Inhibitor experiments revealed that temozolomide-induced senescence was initiated by damage recognition through the MRN complex, activation of the ATR/CHK1 axis of the DNA damage response pathway, and mediated by degradation of CDC25c. Temozolomide-induced senescence required functional p53 and was dependent on sustained p21 induction. p53-deficient cells, not expressing p21, failed to induce senescence, but were still able to induce a G2–M arrest. p14 and p16, targets of p53, were silenced in our cell system and did not seem to play a role in temozolomide-induced senescence. In addition to p21, the NF-κB pathway was required for senescence, which was accompanied by induction of the senescence-associated secretory phenotype. Upon temozolomide exposure, we found a strong repression of the mismatch repair proteins MSH2, MSH6, and EXO1 as well as the homologous recombination protein RAD51, which was downregulated by disruption of the E2F1/DP1 complex. Repression of these repair factors was not observed in G2–M arrested p53-deficient cells and, therefore, it seems to represent a specific trait of temozolomide-induced senescence.

Significance:
These findings reveal a mechanism by which the anticancer drug temozolomide induces senescence and downregulation of DNA repair pathways in glioma cells.
Anti-MET VHH Pool Overcomes MET-Targeted Cancer Therapeutic Resistance
Authors: Su Zhipeng , Han Yunchun , Sun Qichen , Wang Xiaoxiao , Xu Ting , Xie Wei , Huang Xing 
Published: October 2018

Abstract
Receptor tyrosine kinase MET and its ligand hepatocyte growth factor (HGF) play crucial roles in many human malignancies. Numerous drugs have been developed against kinase center of MET or HGF-mediated activation; however, the outcomes in patients are not so promising. Increasing evidence show that MET has kinase-independent effects on tumorigenesis and dissemination, which explains the low efficacy in kinase inhibition-based strategy. VHH is the recombinant variable region of Camelid heavy-chain antibody. As a nanoscale antigen-binding unit, VHH has become an appealing drug candidate in cancer therapy. In our study, we choose a novel strategy to construct an anti-MET VHH pool against the whole ecto-domain of MET. Comparing to monoclonal antibody or single VHH, the anti-MET VHH pool strongly promotes MET degradation through Clathrin-dependent endo-lysosomal pathway. Thus, the anti-MET VHH pool not only blocks kinase activity of MET, but also reduces protein level of MET. As a consequence, anti-MET VHH pool dramatically suppresses cancer cell proliferation, viability, and colony formation in vitro, and inhibits tumorigenesis and growth in mice. Taken together, VHH pool-based strategy greatly improves MET-targeted therapeutic effects on cancer.
Markers of Basement Membrane Remodeling Are Associated With Higher Mortality in Patients With Known Atherosclerosis
Authors: Holm Nielsen Signe , Tengryd Christoffer , Edsfeldt Andreas , Brix Susanne , Genovese Federica , Bengtsson Eva , Karsdal Morten , Leeming Diana J. , Nilsson Jan , Goncalves Isabel 
Published: October 2018

Background
Patients with atherosclerosis have a high risk of cardiovascular events and death. Atherosclerosis is characterized by accumulation of lipids, cells and extracellular matrix proteins in the intima. We hypothesized that dysregulated remodeling of the basement membrane proteins may be associated with clinical outcomes in patients with atherosclerosis.

Methods and Results

Neoepitope fragments of collagen type
IV
(C4M) and laminin (
LG
1M) were assessed by
ELISA
s in serum from 787 endarterectomy patients.
Matrix metalloproteinase
s were measured using proximity extension assay and correlated to C4M and
LG
1M levels using Spearman correlations. A total of 473 patients were followed up for 6 years using national registers, medical charts, and telephone interviews. The incidence of
cardiovascular
events,
cardiovascular
mortality, and all‐cause mortality were associated to levels of C4M and
LG
1M using Kaplan–Meier curves and Cox regression analyses. A total of 101 patients had
cardiovascular
events, 39 died of
cardiovascular
mortality, and 64 patients died from all‐cause mortality. C4M levels were increased in patients with symptomatic carotid atherosclerotic disease before surgery (
P
=0.048). High C4M and
LG
1M levels were associated with increased risk of all‐cause mortality (
P
=0.020 and 0.031, respectively) and predicted all‐cause death together with glomerular filtration rate and diabetes mellitus.

Conclusions

High
LG
1M and C4M levels were associated with all‐cause mortality, together with glomerular filtration rate and diabetes mellitus. These novel biomarkers need further evaluation but might be tools to identify high‐risk patients.
8‐Aminoguanine Induces Diuresis, Natriuresis, and Glucosuria by Inhibiting Purine Nucleoside Phosphorylase and Reduces Potassium Excretion by Inhibiting Rac1
Authors: Jackson Edwin K. , Mi Zaichuan , Kleyman Thomas R. , Cheng Dongmei 
Published: October 2018

Background

8‐Aminoguanosine and 8‐aminoguanine are K
+
‐sparing natriuretics that increase glucose excretion. Most effects of 8‐aminoguanosine are due to its metabolism to 8‐aminoguanine. However, the mechanism by which 8‐aminoguanine affects renal function is unknown and is the focus of this investigation.

Methods and Results

Because 8‐aminoguanine has structural similarities with inhibitors of the epithelial sodium channel (ENaC), Na
+
/H
+
exchangers, and adenosine A
1
receptors, we examined the effects of 8‐aminoguanine on
EN
aC activity in mouse collecting duct cells, on intracellular
pH
of human proximal tubular epithelial cells, on responses to a selective A
1
‐receptor agonist in vivo, and on renal excretory function in A
1
‐receptor knockout rats. These experiments showed that 8‐aminoguanine did not block
EN
aC, Na
+
/H
+
exchangers, or A
1
receptors. Because Rac1 enhances activity of mineralocorticoid receptors and some guanosine analogues inhibit Rac1, we examined the effects of 8‐aminoguanine on Rac1 activity in mouse collecting duct cells. Rac1 activity was significantly inhibited by 8‐aminoguanine. Because in vitro 8‐aminoguanine is a purine nucleoside phosphorylase (
PNP
ase) inhibitor, we examined the effects of a natriuretic dose of 8‐aminoguanine on urinary excretion of
PNP
ase substrates and products. 8‐Aminoguanine increased and decreased, respectively, urinary excretion of
PNP
ase substrates and products. Next we compared in rats the renal effects of intravenous doses of 9‐deazaguanine (
PNP
ase inhibitor) versus 8‐aminoguanine. 8‐Aminoguanine and 9‐deazaguanine induced similar increases in urinary Na
+
and glucose excretion, yet only 8‐aminoguanine reduced K
+
excretion. Nsc23766 (Rac1 inhibitor) mimicked the effects of 8‐aminoguanine on K
+
excretion.

Conclusions

8‐Aminoguanine increases Na
+
and glucose excretion by blocking
PNP
ase and decreases K
+
excretion by inhibiting Rac1.
Description of Bursaphelenchus rockyi n. sp. (Nematoda: Aphelenchoididae) in peat moss from Russia
Authors: Wang Xu , Fang Yiwu , Maria Munawar , Gu Jianfeng , Ge Jianjun 
Published: October 2018

Summary
Bursaphelenchus rockyi n. sp., isolated in Peking, China, from peat moss imported from Russia, is described. It is characterised by a lateral field with four lines, excretory pore located at the base of the nerve ring or slightly posterior, spicule 15.9 (15.1-17.3) μm long along the chord and with high condylus and a rounded tip, rostrum triangular or conical with bluntly pointed tip, lamina curvature becoming more pronounced at 60% of total length, six caudal papillae with P3 and P4 adjacent to each other, bursa small, starting posterior to P4, vulval lips hemispherical and protruding, and tail conical with finely rounded or mucronated terminus. The new species belongs to the fungivorus-group and is most similar to B. arthuri, B. arthuroides, B. fungivorus and B. seani, but can be distinguished from related species by morphological and sequencing results.
Cannabis Reform, ‘Medical and Scientific Purposes’ and the Vienna Convention on the Law of Treaties
Authors: Lines Rick , Barrett Damon 
Published: October 2018

Abstract
Treaty interpretation has long been a subject of interest for international legal scholars. However, it is only recently that advocates for drug policy reform have taken up these questions. This article examines the proposition put forward by several authors that a legally regulated market in cannabis may be permissible under the international drug control treaties if considered as a policy ‘experiment’. These authors contend that such measures conform to the general obligation of the Single Convention on Narcotic Drugs to limit uses of cannabis ‘strictly to medical and scientific purposes’. Reviewing this position using the formal methods set out in Articles 31 and 32 of the Vienna Convention on the Law of Treaties, we conclude the interpretation proposed is untenable. While we share with these authors the objective of wider drug policy reform, we find the arguments supporting this position weak, and based on absent, flawed or incomplete interpretive methodology.
Regulated Legalization of Cannabis through Positive Human Rights Obligations and Inter se Treaty Modification
Authors: van Kempen Piet Hein , Fedorova Masha 
Published: October 2018

Abstract
Although the UN narcotic drugs conventions do not allow states parties to legalize cannabis cultivation and trade for recreational use, there are possibilities for states to do so anyhow while staying within the boundaries of international public law. A first option concerns positive human rights obligations, i.e. obligations that require states to take measures in order to offer the best protection of human rights. If a state convincingly argues that with cannabis regulation positive human rights obligations to protect society can be more effectively achieved than under a prohibitive approach, the priority position of human rights obligations over the drugs conventions can justify such regulation. The second option regards the modification of the drugs conventions through an inter se agreement on cannabis regulation between certain of the states parties only. The positive human rights approach and the inter se possibility can strengthen each other and are a supreme combination.
Linkage between Interannual Variation of the East Asian Intraseasonal Oscillation and Mei-Yu Onset
Authors: Yao Yonghong , Lin Hai , Wu Qigang 
Published: October 2018

AbstractThe mei-yu onset over the middle to lower reaches of the Yangtze River Valley (MLYRV) varies considerably from early June to mid-July, which leads to large interannual changes in rainy-season length, total summer rainfall, and flooding potential. Previous studies have investigated the impact of El Niño–Southern Oscillation (ENSO) on the mei-yu onset. This study shows that a strong (weak) East Asian and western North Pacific (EAWNP) intraseasonal oscillation (ISO) in spring leads to an early (late) onset of the mei-yu over the MLYRV, and this ISO–mei-yu relationship is attributed to different types of ENSO in the preceding winter. A strong EAWNP ISO in spring is related to an eastern Pacific El Niño (EP El Niño) in the previous winter, and negative sea surface temperature (SST) anomalies in the eastern Indian Ocean and the South China Sea (SCS) in May, which can cause an early onset of the South China Sea summer monsoon that also favors an early mei-yu onset. In contrast, a weak EAWNP ISO in spring is associated with a central Pacific El Niño (CP El Niño) before April, but with an EP El Niño after April, and positive SST anomalies in both the eastern Indian Ocean and the SCS in May. A statistical forecast model combining the intensity of spring EAWNP ISO, CP ENSO, and EP ENSO indices shows a high prediction skill of the observed mei-yu onset date.
All-Sky Radiance Assimilation of ATMS in HWRF: A Demonstration Study
Authors: Wu Ting-Chi , Zupanski Milija , Grasso Lewis D. , Kummerow Christian D. , Boukabara Sid-Ahmed 
Published: October 2018

Abstract
Satellite all-sky radiances from the Advanced Technology Microwave Sounder (ATMS) are assimilated into the Hurricane Weather Research and Forecasting (HWRF) Model using the hybrid Gridpoint Statistical Interpolation analysis system (GSI). To extend the all-sky capability recently developed for global applications to HWRF, some modifications in HWRF and GSI are facilitated. In particular, total condensate is added as a control variable, and six distinct hydrometeor habits are added as state variables in hybrid GSI within HWRF. That is, clear-sky together with cloudy and precipitation-affected satellite pixels are assimilated using the Community Radiative Transfer Model (CRTM) as a forward operator that includes hydrometeor information and Jacobians with respect to hydrometeor variables. A single case study with the 2014 Atlantic storm Hurricane Cristobal is used to demonstrate the methodology of extending the global all-sky capability to HWRF due to ATMS data availability. Two data assimilation experiments are carried out. One experiment uses the operational configuration and assimilates ATMS radiances under the clear-sky condition, and the other experiment uses the modified HWRF system and assimilates ATMS radiances under the all-sky condition with the inclusion of total condensate update and cycling. Observed and synthetic Geostationary Operational Environmental Satellite (GOES)-13 data along with Global Precipitation Measurement Mission (GPM) Microwave Imager (GMI) data from the two experiments are used to show that the experiment with all-sky ATMS radiances assimilation has cloud signatures that are supported by observations. In contrast, there is lack of clouds in the initial state that led to a noticeable lag of cloud development in the experiment that assimilates clear-sky radiances.
From ‘History as Told’ to ‘History as Experienced’: Contextualizing the Uses of the Past
Authors: Lubinski Christina 
Published: October 2018

Research has made great strides in understanding how and why organizational actors use the past. So far, scholars have largely focused the level of analysis on the organization, without exploring the intertwined nature of historical claim-making with the organizational field or society at large. This article extends the status quo by conceptualizing the role of context for organizational uses-of-the-past. It identifies three key aspects of context that shape how history contributes to the social construction of reality: the existence of multiple audiences, the landscape of pre-existing historical narratives and the experience of social practices giving credibility to historical claims. By analysing the historical case of German business in colonial India, the paper makes three broader claims that could move research toward a more contextualized conception of the uses-of-the-past: (i) historical claims are validated in a continuous dialogue with multiple audiences; (ii) they revise previously existing narratives by critiquing or ‘outpasting’, i.e. invoking earlier origins; (iii) they often result in ‘rhetorical frictions’ that require continuous and skilful history revisions to mitigate emerging conflicts in their reception. By contextualizing the uses-of-the-past in this way, the paper moves beyond ‘hypermuscular’ organizational actors bending history to their will and foregrounds the situated nature of historical rhetoric.