bluuebunny/crossref_metadata_2025_split huggingface dataset:
Energetics of the Western Hemisphere Circulation Pattern
Authors: Tan Xin , Bao Ming , Ren Xuejuan 
Published: August 2019

Abstract
The Western Hemisphere (WH) circulation pattern, identified by self-organizing maps cluster analysis, is a low-frequency atmospheric regime that influences the fluctuations of large-scale circulation over the North Pacific–North American–North Atlantic areas. The reanalysis datasets from ECMWF are used to estimate the energetics of the WH pattern in this study. The composite results based on monthly WH events reveal that the kinetic energy (KE) associated with the WH pattern is maintained through the barotropic conversion from the climatological-mean westerlies, mainly in the Atlantic jet exit regions. The KE could also be gained through the barotropic feedback forcing from transient eddies. The corresponding baroclinic conversion of available potential energy (APE) from the climatological-mean state, which contributes most efficiently to the energy maintenance of the WH pattern, is obvious in the middle and lower troposphere, owing to the thermal contrast of the colder continent and warmer ocean over the North America–North Atlantic sector. The baroclinic conversion associated with the heat flux on the climatological temperature gradient is consistent with the southwestward-tilting height anomalies from 850 to 500 hPa. The baroclinic feedback from transient eddies contributes negatively to the energy conversion and destroys the maintenance of the WH pattern.
De-escalating chemotherapy for stage II colon cancer?
Authors: Fu Jianfei , Wu Lunpo , Ge Chenyang , Xu Tiantian , Li Dan , Fu Wei , Wang Liangjing , Du Jinlin 
Published: August 2019

Background: Although adjuvant chemotherapy is recommended for patients with stage II colon cancer characterized by poor prognostic features, its pros and cons remain a controversial issue. We aim to evaluate the real effectiveness of chemotherapy on stage II colon cancer as well as select suitable patients. Methods: Patients during 1988–2013 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The competing risk regression model and propensity score matching method were used to evaluate colon-cancer-specific death (CCSD) and non-CCSD. Also, a competing-risk nomogram was constructed to identify risk of patients. Risk score (RS) was calculated according to nomogram. Results: A total of 58,133 patients were included, 25.66% received chemotherapy, and 74.34% were without chemotherapy. In total, 19.95% and 25.78% of patients died of CCSD and non-CCSD, respectively. Univariate and multivariate analyses showed that receiving chemotherapy appears to be associated with more CCSD and less non-CCSD (HR 1.23, 95% CI 1.18–1.28; HR 0.45, 95% CI 0.43–0.47, respectively), even after adjustment for covariates and propensity score weighting. A competing-risk nomogram was established; the model was relatively good with a C-index of 0.661. Based on the RS, risk stage could only predict prognosis but failed to predict the benefit from chemotherapy. Conclusions: The value of chemotherapy is much less than we thought. It is time to de-escalate chemotherapy for stage II colon cancer. CCSD, rather than overall survival, should be considered as an appropriate primary end point for future trials in stage II colon cancer.
Karonudib is a promising anticancer therapy in hepatocellular carcinoma
Authors: Hua Xiangwei , Sanjiv Kumar , Gad Helge , Pham Therese , Gokturk Camilla , Rasti Azita , Zhao Zhenjun , He Kang , Feng Mingxuan , Zang Yunjin , Zhang Jianjun , Xia Qiang , Helleday Thomas , Warpman Berglund Ulrika 
Published: August 2019

Background: Hepatocellular carcinoma (HCC) is the most common form of liver cancer and is generally caused by viral infections or consumption of mutagens, such as alcohol. While liver transplantation and hepatectomy is curative for some patients, many relapse into disease with few treatment options such as tyrosine kinase inhibitors, for example, sorafenib or lenvatinib. The need for novel systemic treatment approaches is urgent. Methods: MTH1 expression profile was first analyzed in a HCC database and MTH1 mRNA/protein level was determined in resected HCC and paired paracancerous tissues with polymerase chain reaction (PCR) and immunohistochemistry. HCC cancer cell lines were exposed in vitro to MTH1 inhibitors or depleted of MTH1 by siRNA. 8-oxoG was measured by the modified comet assay. The effect of MTH1 inhibition on tumor growth was explored in HCC xenograft in vivo models. Results: MTH1 protein level is elevated in HCC tissue compared with paracancerous liver tissue and indicates poor prognosis. The MTH1 inhibitor Karonudib (TH1579) and siRNA effectively introduce toxic oxidized nucleotides into DNA, 8-oxoG, and kill HCC cell lines in vitro. Furthermore, we demonstrate that HCC growth in a xenograft mouse model in vivo is efficiently suppressed by Karonudib. Conclusion: Altogether, these data suggest HCC relies on MTH1 for survival, which can be targeted and may open up a novel treatment option for HCC in the future.
Articular Cartilage Defects of the Glenohumeral Joint: A Systematic Review of Treatment Options and Outcomes
Authors: Fiegen Anthony , Leland Devin P. , Bernard Christopher D. , Krych Aaron J. , Barlow Jonathan D. , Dahm Diane L. , Camp Christopher L. 
Published: August 2019

Objective To report radiographic and magnetic resonance imaging findings, patient-reported outcomes, and complications and/or reoperations following nonarthroplasty surgical intervention for focal glenohumeral cartilage defects. Design A literature search was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Patients were included if they possessed a chondral defect of the humeral head, glenoid, or both, which had been treated with a joint preserving nonarthroplasty procedure. Risk of bias assessment was performed using the Methodological Index for Non-Randomized Studies scoring system. Study demographics, surgical technique, imaging findings, patient-reported outcomes, complications, failures, and reoperations were collected. Results Fourteen studies with 98 patients (100 shoulders) met the inclusion criteria. Patient ages ranged from 7 to 74 years. The nonarthroplasty surgical techniques utilized included microfracture (67 shoulders), osteochondral transplantation (28 shoulders), chondrocyte transplantation (4 shoulders), and internal fixation (1 shoulder). The rates of radiographic union and progression of osteoarthritis ranged between 90% to 100% and 57% to 100%, respectively. Visual analog scores ranged from 0 to 1.9 at final follow-up. Mean postoperative ASES (American Shoulder and Elbow Surgeons) shoulder scores ranged from 75.8-100. Mean postoperative CSS (Constant Shoulder Score) scores ranged from 83.3-94. Mean postoperative SSV (Subjective Shoulder Value) ranged from 70% to 99%. Failure and reoperation rates ranged between 0% to 35% and 0% to 30%, respectively, with the most common reoperation being conversion to prosthetic arthroplasty. Conclusions In this systematic review, nonarthroplasty surgical techniques demonstrated acceptable rates of radiographic healing, improved patient reported outcomes, minimal complications, and low rates of failure or reoperation. Joint preserving techniques are likely viable options to prolong function of the native shoulder and provide short- to midterm pain relief in young and highly active patients. Level of Evidence Level IV.
On the application of the IMA−CNMNC dominant-valency rule to complex mineral compositions
Authors: Bosi Ferdinando , Hatert Frédéric , Hålenius Ulf , Pasero Marco , Miyawaki Ritsuro , Mills Stuart J. 
Published: August 2019

AbstractMineral species should be identified by an end-member formula and by using the dominant-valency rule as recommended by the IMA–CNMNC. However, the dominant-end-member approach has also been used in the literature. These two approaches generally converge, but for some intermediate compositions, significant differences between the dominant-valency rule and the dominant end-member approach can be observed. As demonstrated for garnet-supergroup minerals, for example, the end-member approach is ambiguous, as end-member proportions strongly depend on the calculation sequence. For this reason, the IMA–CNMNC strongly recommends the use of the dominant-valency rule for mineral nomenclature, because it alone may lead to unambiguous mineral identification. Although the simple application of the dominant-valency rule is successful for the identification of many mineral compositions, sometimes it leads to unbalanced end-member formulae, due to the occurrence of a coupled heterovalent substitution at two sites along with a heterovalent substitution at a single site. In these cases, it may be useful to use the site-total-charge approach to identify the dominant root-charge arrangement on which to apply the dominant-constituent rule. The dominant-valency rule and the site-total-charge approach may be considered two procedures complementary to each other for mineral identification. Their critical point is to find the most appropriate root-charge and atomic arrangements consistent with the overriding condition dictated by the end-member formula. These procedures were approved by the IMA−CNMNC in May 2019.
A method for noninvasive prenatal diagnosis of monogenic autosomal recessive disorders
Authors: Cutts Anthony , Vavoulis Dimitrios V. , Petrou Mary , Smith Frances , Clark Barnaby , Henderson Shirley , Schuh Anna 
Published: August 2019

Abstract
Using sickle cell disease as a model, Cutts et al describe a highly sensitive method for prenatal diagnosis of known single-gene defects using next-generation sequencing of maternal plasma cell-free DNA.
The impact on malaria of biannual treatment with azithromycin in children age less than 5 years: a prospective study
Authors: Bloch Evan M. , Munoz Beatriz , Mrango Zakayo , Weaver Jerusha , Mboera Leonard E. G. , Lietman Tom M. , Sullivan David J. , West Sheila K. 
Published: August 2019

AbstractBackgroundThe MORDOR study, a cluster randomized clinical trial, showed that single-dose azithromycin (20 mg/kg) administered biannually for 2 years to preschool children reduced mortality; a study was conducted to determine its effect on clinical symptomatic episodes of malaria as a potential mechanism for mortality benefit.MethodsA randomized control trial (RCT) was conducted, whereby 30 randomly selected communities in Kilosa District, Tanzania were randomized to receive 6-monthly treatment of children ages 1–59 months with single-dose azithromycin (20 mg/kg) vs. placebo. A prospective cohort study was nested within the RCT: children, aged 1 to 35 months at baseline, were randomly selected in each community and evaluated at 6-monthly intervals for 2 years. At each visit, the children were assessed for recent or ongoing fever and anti-malarial treatment; a rapid diagnostic test (RDT) for malaria was performed. The two major outcomes of interest were prevalence of RDT positivity and clinical malaria. The latter was defined as RDT-positivity with fever at time of evaluation and/or reported fever in the 3 days prior to evaluation. Methods that account for correlations at community level and within individuals over time were used to evaluate associations.ResultsAt baseline, the prevalence rates in the children in the azithromycin and placebo arms were 17.6% vs. 15.5% for RDT positivity (p = 0.76) and 6.1% vs. 4.3% (p = 0.56) for clinical malaria. There was a decline in both RDT-positivity and clinical malaria over time in both arms. The difference by treatment assignment was not significant for clinical malaria; it was significant for RDT-positivity with greater odds of decline in the placebo arm (p = 0.01).ConclusionsLack of evidence for a significant difference in the prevalence of clinical malaria in children at any visit following treatment suggests that the effect of single-dose azithromycin on malaria is at best transient and limited in scope. Chance overrepresentation of non-seasonal transmission in the communities in the azithromycin arm may account for higher rates of RDT-positivity and less decline over time.Trial registrationClinicaltrials.gov NCT02047981
Longer collagen fibers trigger multicellular streaming on soft substrates via enhanced forces and cell–cell cooperation
Authors: Sarker Bapi , Bagchi Amrit , Walter Christopher , Almeida José , Pathak Amit 
Published: August 2019

ABSTRACT
Grouped cells often leave large cell colonies in the form of narrow multicellular streams. However, it remains unknown how collective cell streaming exploits specific matrix properties, like stiffness and fiber length. It is also unclear how cellular forces, cell–cell adhesion and velocities are coordinated within streams. To independently tune stiffness and collagen fiber length, we developed new hydrogels and discovered invasion-like streaming of normal epithelial cells on soft substrates coated with long collagen fibers. Here, streams arise owing to a surge in cell velocities, forces, YAP activity and expression of mesenchymal marker proteins in regions of high-stress anisotropy. Coordinated velocities and symmetric distribution of tensile and compressive stresses support persistent stream growth. Stiff matrices diminish cell–cell adhesions, disrupt front–rear velocity coordination and do not promote sustained fiber-dependent streaming. Rac inhibition reduces cell elongation and cell–cell cooperation, resulting in a complete loss of streaming in all matrix conditions. Our results reveal a stiffness-modulated effect of collagen fiber length on collective cell streaming and unveil a biophysical mechanism of streaming governed by a delicate balance of enhanced forces, monolayer cohesion and cell–cell cooperation.
This article has an associated First Person interview with the first authors of the paper.
The RBG-1–RBG-2 complex modulates autophagy activity by regulating lysosomal biogenesis and function in C. elegans
Authors: Wang Zhaoyu , Zhao Hongyu , Yuan Chongzhen , Zhao Dongfeng , Sun Yanan , Wang Xiaochen , Zhang Hong 
Published: August 2019

ABSTRACT
Vici syndrome is a severe and progressive multisystem disease caused by mutations in the EPG5 gene. In patient tissues and animal models, loss of EPG5 function is associated with defective autophagy caused by accumulation of non-degradative autolysosomes, but very little is known about the mechanism underlying this cellular phenotype. Here, we demonstrate that loss of function of the RBG-1–RBG-2 complex ameliorates the autophagy defect in C. elegans epg-5 mutants. The suppression effect is independent of the complex's activity as a RAB-3 GAP and a RAB-18 GEF. Loss of rbg-1 activity promotes lysosomal biogenesis and function, and also suppresses the accumulation of non-functional autolysosomes in epg-5 mutants. The mobility of late endosome- and lysosome-associated RAB-7 is reduced in epg-5 mutants, and this defect is rescued by simultaneous loss of function of rbg-1. Expression of the GDP-bound form of RAB-7 also promotes lysosomal biogenesis and suppresses the autophagy defect in epg-5 mutants. Our study reveals that the RBG-1–RBG-2 complex acts by modulating the dynamics of membrane-associated RAB-7 to regulate lysosomal biogenesis, and provides insights into the pathogenesis of Vici syndrome.
Study protocol for a process evaluation of a cluster randomised controlled trial to reduce potentially inappropriate prescribing and polypharmacy in patients with multimorbidity in Irish primary care (SPPiRE)
Authors: Kyne Karen , McCarthy Caroline , Kiely Bridget , Smith Susan M. , Clyne Barbara ,   SPPiRE Study team
Published: August 2019

Background: Multimorbidity (the presence of two or more chronic conditions) is associated with poorer health outcomes, particularly for patients with significant polypharmacy (≥15 medications), due to the higher risk of adverse events and drug interactions. The SPPiRE study will assess the effectiveness of a complex intervention to support general practitioners (GPs) to reduce potentially inappropriate prescribing and consider deprescribing in older people with multimorbidity and significant polypharmacy. The aim of the SPPiRE process evaluation is to understand how and why the intervention is effective or ineffective and to explore the potential for system wide implementation of the intervention using the Medical Research Council general themes of context, implementation and mechanism of impact. Methods: The SPPiRE study is a clustered randomised controlled trial (RCT), aiming to recruit 55 general practices and 400 patients (≥65 years) on ≥15 medications throughout the Republic of Ireland. This mixed-methods process evaluation of the SPPiRE study will integrate both quantitative and qualitative data. Quantitative data will be collected on use of the intervention elements and from GP questionnaires. Qualitative data will be collected from semi-structured telephone interviews with all intervention GPs and a purposeful sample of patients from intervention practices. The topic guide will explore barriers and facilitators to participation and implementation of the intervention. Quantitative data will be analysed using descriptive statistics. Interviews will be transcribed and analysed using thematic analysis. Quantitative and qualitative data will be then be integrated. Discussion: The SPPiRE cluster RCT will provide evidence regarding the effectiveness and practicability of delivering a structured medication review in reducing polypharmacy and potentially inappropriate prescribing for patients with multimorbidity. This process evaluation will provide information on how the intervention was implemented, how it was or was not effective and the potential for a system wide implementation. Trial registration: ISRCTN 12752680, registration: 20/10/2016
Toward a Framework for Outcome-Based Analytical Performance Specifications: A Methodology Review of Indirect Methods for Evaluating the Impact of Measurement Uncertainty on Clinical Outcomes
Authors: Smith Alison F , Shinkins Bethany , Hall Peter S , Hulme Claire T , Messenger Mike P 
Published: August 2019

AbstractBACKGROUNDFor medical tests that have a central role in clinical decision-making, current guidelines advocate outcome-based analytical performance specifications. Given that empirical (clinical trial-style) analyses are often impractical or unfeasible in this context, the ability to set such specifications is expected to rely on indirect studies to calculate the impact of test measurement uncertainty on downstream clinical, operational, and economic outcomes. Currently, however, a lack of awareness and guidance concerning available alternative indirect methods is limiting the production of outcome-based specifications. Therefore, our aim was to review available indirect methods and present an analytical framework to inform future outcome-based performance goals.CONTENTA methodology review consisting of database searches and extensive citation tracking was conducted to identify studies using indirect methods to incorporate or evaluate the impact of test measurement uncertainty on downstream outcomes (including clinical accuracy, clinical utility, and/or costs). Eighty-two studies were identified, most of which evaluated the impact of imprecision and/or bias on clinical accuracy. A common analytical framework underpinning the various methods was identified, consisting of 3 key steps: (a) calculation of “true” test values; (b) calculation of measured test values (incorporating uncertainty); and (c) calculation of the impact of discrepancies between (a) and (b) on specified outcomes. A summary of the methods adopted is provided, and key considerations are discussed.CONCLUSIONSVarious approaches are available for conducting indirect assessments to inform outcome-based performance specifications. This study provides an overview of methods and key considerations to inform future studies and research in this area.
Hi-Fi, Lo-Fi, No-Fi, and Wi-Fi Interpretation
Authors: Leone Massimo 
Published: August 2019

Abstract
The article seeks to establish a dialog, from a semiotic point of view, with the grand cartography of methods in literary criticism proposed by Prof. Zhang Jiang in his famous essay “Imposed interpretation.” While acknowledging that Prof. Zhang Jiang identifies the most crucial weak points of the semiotic methodology, the article nevertheless takes these criticisms as occasions to improve the approach of semiotics, as regards especially the following oppositions: diagrammatic over-schematization versus quest for a more judicious application of the method; overenthusiastic adoption of mathematical formulas versus cautious cross-fertilization between humanities and scientific thought; frantic pursuance of theoretical uniformity versus humble acceptance of literary idiosyncrasies; fundamentalist proclamation of the self-reliance of the text versus thoughtful consideration of the evident links between the text and its contexts. This new theoretical approach, wherein traditional semiotics improves itself in dialog with Prof. Zhang Jiang’s criticisms, is exemplified with reference to the concept of interpretive fidelity, which is categorized into different levels and dimensions of adhesion between the textual structure and the discourse of the meta-language interpreting it: hi-fi, low-fi, no-fi, and wi-fi interpretation.
On Sign Lies
Authors: Zhang Suojun , Jia Hongwei 
Published: August 2019

Abstract
People communicate with each other in and by the signs around them. The sender might intentionally or unintentionally tell lies to the addressee through signs in order to achieve special effects or purposes which are contrary to fact or reality. These signs can thus be termed as sign lies. This interview with Prof. Hongwei Jia addresses the nature, property, classification, boundaries, and application of sign lies so as to improve the concept of sign lies proposed by Umberto Eco. Along with some new achievements in the understanding of sign lies, some problems or difficulties that scholars will confront in the coming years are also put forward.
Impact of Harmonics on Power Transformer Losses and Capacity Using Open DSS
Authors: Maan Jaspreet Singh , Singh Sanjeev , Singh Amanpreet 
Published: August 2019

Abstract
Harmonics in the power system are increasing due to increased use of power electronic devices in load. Power electronic devises results in nonlinear loading of the distribution system network creating problem of harmonics. Harmonics effects the distribution transformers in distribution system as well as Power Transformer at the grid substation resulting in more losses, production of extra heat, reduction in efficiency and accelerated ageing of insulation. In this paper a feeder of PSPCL is modelled using EPRI open source distribution system simulator (Open DSS) and effect of harmonics due to nonlinear loading measured from distribution system on the power transformer at grid substation supplying the modelled feeder is evaluated for capacity reduction and loss of life as per IEEE standard C57.110–1998.
A modality-based approach to the United Nations Security Council’s ambiguous positioning in the resolutions on the Syrian armed conflict
Authors: Rosa María Victoria Martín de la , Romero Elena Domínguez 
Published: August 2019

AbstractThis paper examines the role of deontic and epistemic central modality as a discursive strategy to express vagueness in the United Nations Security Council Resolutions on the Syrian armed conflict. The paper follows a corpus-based methodology with a two-fold objective: (i) identification, quantification and analysis of the central modal verbs retrieved from the resolutions, and (ii) the description of the communicative functions performed by these verbs. Our ultimate aim is to reveal the use of deliberate flexible language leading to ambiguous positioning towards the Syrian armed conflict in the United Nations Security Council Resolutions which have been issued since 2012. The consequences associated with the institutional use of flexible language and ambiguous positioning in the resolutions under study will also be accounted for.