bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness assessment of riluzole in the prevention of oxaliplatin-induced peripheral neuropathy: RILUZOX-01: protocol of a randomised, parallel, controlled, double-blind and multicentre study by the UNICANCER-AFSOS Supportive Care intergroup
Authors: Kerckhove Nicolas , Busserolles Jérome , Stanbury Trevor , Pereira Bruno , Plence Valérie , Bonnetain Franck , Krakowski Ivan , Eschalier Alain , Pezet Denis , Balayssac David 
Published: June 2019

IntroductionMost patients (>70%) experience acute neuropathic symptoms shortly after oxaliplatin infusions. These symptoms are not always resolved between infusions. Overall, 30%–50% of patients suffer from chronic oxaliplatin-induced peripheral neuropathy (OIPN). This cumulative and dose-dependent sensory neuropathy limits compliance or results in oxaliplatin-based chemotherapies to be substituted with less neurotoxic agents. These treatment changes impair clinical outcomes, and may be associated with comorbidities, such as distress, depression and anxiety. Currently, no drug used to prevent or treat OIPN is sufficiently effective to be used routinely in clinical practice. There is, thus, an unmet therapeutic need to reduce the intensity of and/or prevent OIPN. We hypothesised that riluzole would be an excellent candidate to address this public health issue. Riluzole is approved for treating amyotrophic lateral sclerosis. In animals, there is a beneficial effect on sensorimotor and pain disorders, as well as related comorbidities, after repeated administration of oxaliplatin. In humans, riluzole has shown neuroprotective, anxiolytic and antidepressive effects.Methods and analysisRILUZOX-01 trial was designed as a randomised, controlled, double-blind study to evaluate the efficacy of riluzole to prevent OIPN. Patients with colorectal cancer and initiating adjuvant oxaliplatin-based chemotherapy are eligible. Patients (n=210) will be randomly assigned to either riluzole or placebo, concomitantly with chemotherapy. The primary endpoint is the change in OIPN intensity, assessed by the sensory scale of the QLQ-CIPN20, after six 2-week cycles of chemotherapy. Secondary endpoints include incidence and severity of neuropathy, grade of sensory neuropathy, intensity and features of neuropathic pain, health-related quality of life, disease-free survival, overall survival and safety.Ethics and dessiminationThe study was approved by a French ethics committee (ref:39/18_1, ‘Comité de Protection des Personnes’ Ouest-IV, France) and plans to start enroling patients in September 2019. The trial is registered in EudraCT and clinicaltrials.gov.Trial registration numberN°2017-002320-25;NCT03722680
Efficacy of the bile leak test using contrast-enhanced intraoperative ultrasonic cholangiography in liver resection: a study protocol for a non-randomised, prospective, off-label, single-arm trial
Authors: Tanaka Motofumi , Kido Masahiro , Kuramitsu Kaori , Komatsu Shohei , Awazu Masahide , Gon Hidetoshi , Tsugawa Daisuke , Mukubo Hideyo , Toyama Hirochika , Fukumoto Takumi 
Published: June 2019

IntroductionBile leak is still a major complication after liver resection to be improved. To intraoperatively detect this adverse complication, leak test is commonly performed after hepatic resection. However, by the conventional leak test, it is often difficult to know whether the test reagent reaches to intrahepatic bile duct near cut surface of liver with adequate volume and pressure to identify the existence of bile leak. Thus, in order to perform leak test more accurately, this study aims to evaluate the efficacy and safety of the leak test using contrast-enhanced intraoperative ultrasonic cholangiography (CE-IOUSC), which was reported by our group as a procedure for detection of bile duct.Methods and analysisThe current study is a non-randomised, prospective, off-label, single-arm clinical trial for patients who undergo liver resection. A total of 100 patients will be enrolled. After completion of liver resection, the leak test is performed with CE-IOUSC using Sonazoid as a contrast agent to visualise dye injection into the intrahepatic bile duct. The primary endpoint is the success of the leak test, defined as clear visualisation of intrahepatic bile duct around cut surface by ultrasonography that indicates enough volume of dye injection. Secondary endpoints are postoperative bile leak and all adverse events related to CE-IOUSC. The findings obtained through this study will establish this procedure to assist surgeons for adequately performing the leak test, precisely detecting intraoperative biliary leak strictly and reducing postoperative bile leak.Ethics and disseminationThe protocol is approved by Institutional Review Boards of Kobe University Hospital (No.290069). Our findings will be widely disseminated through conference presentations and peer-reviewed publications.Trial registration numberUMIN000031236 and jRCTs051180027.
Considerable distance to reach 90-90-90 targets among female sex workers, men who have sex with men and transgender women in Port Moresby, Papua New Guinea: findings from a cross-sectional respondent-driven sampling survey
Authors: Hakim Avi J , Badman Steven G , Weikum Damian , Amos Angelyne , Willie Barne , Narokobi Rebecca , Gabuzzi Josephine , Pekon Simon , Kupul Martha , Hou Parker , Aeno Herick , Neo Boli Ruthy , Nembari Joshua , Ase Sophie , Kaldor John M , Vallely Andrew J , Kelly-Hanku Angela 
Published: June 2019

ObjectiveTo characterise the Joint United Nations Programme on HIV/AIDS 90-90-90 cascade among female sex workers (FSW) and men who have sex with men (MSM)/transgender women (TGW) in Port Moresby, Papua New Guinea (PNG).MethodsWe conducted respondent-driven sampling surveys among FSW and MSM/TGW in Port Moresby, PNG from June to October 2016. All participants spoke English or Tok Pisin and were aged >12 years. FSW had to be born female and sell/exchange sex with a male in the past 6 months. MSM/TGW had to be born male and have oral/anal sex with another male-born person in the past 6 months. Participants were interviewed and offered rapid HIV diagnostic and viral load testing. HIV viral suppression (VS) was defined as <1000 copies/mL.ResultsWe recruited 674 FSW and 400 MSM/TGW; HIV prevalence was 15.2% (95% CI 11.7 to 18.8) and 8.5% (95% CI 5.0 to 11.9), respectively. Among FSW living with HIV, 39.0% (95% CI 26.6 to 51.4) self-reported having been diagnosed; of them 79.6% (95% CI 62.7 to 96.5) self-reported being on antiretroviral therapy (ART), and 54.1% (95% CI 31.8 to 76.4) achieved VS. Among MSM/TGW living with HIV, 24.4% (95% CI 4.7 to 44.1) self-reported having been diagnosed; of them 43.9% (95% CI 33.6 to 54.8) self-reported being on ART, and 86.1% (95% CI 71.1 to 93.9) achieved VS.ConclusionsART use among those aware of their HIV status is encouraging. However, the generally low awareness of infection status among FSW and MSM/TGW with HIV and the low VS among FSW on ART indicate an urgent need for innovative strategies to increase testing uptake and ART adherence among these populations. Monitoring drug resistance may be warranted.
Ascending-Price Algorithms for Unknown Markets
Authors: Bei Xiaohui , Garg Jugal , Hoefer Martin 
Published: June 2019

We design a simple ascending-price algorithm to compute a (1 + ε)-approximate equilibrium in Arrow-Debreu markets with weak gross substitute property. It applies to an unknown market setting without exact knowledge about the number of agents, their individual utilities, and endowments. Instead, our algorithm only uses price queries to a global demand oracle. This is the first polynomial-time algorithm for most of the known tractable classes of Arrow-Debreu markets, which computes such an equilibrium with a number of calls to the demand oracle that is polynomial in log 1/ε and avoids heavy machinery such as the ellipsoid method.
Demands can be real-valued functions of prices, but the oracles only return demand values of bounded precision. Due to this more realistic assumption, precision and representation of prices and demands become a major technical challenge, and we develop new tools and insights that may be of independent interest. Furthermore, we give the first polynomial-time algorithm to compute an exact equilibrium for markets with spending constraint utilities. This resolves an open problem posed by Duan and Mehlhorn.
Glutamate Decarboxylase 65 Signals through the Androgen Receptor to Promote Castration Resistance in Prostate Cancer
Authors: Gao Yi , Chen Lu , Du ZunGuo , Gao WenChao , Wu ZhengMing , Liu XiuJuan , Huang Hai , Xu DanFeng , Li QingQuan 
Published: June 2019

Abstract

The transition from an androgen-dependent to a castration-resistant state is a critical event in the progression of prostate cancer. In this study, we compared metabolic pathways between isogenic human androgen-dependent and castration-resistant prostate cancer (CRPC) patient-derived xenograft models, and found consistent activation of the γ-aminobutyric acid (GABA) shunt in CRPC. This difference was the result of phosphorylation and activation of glutamate decarboxylase 65 (GAD65), which synthesizes GABA from glutamate by decarboxylation. Mechanistic investigation showed that GABA binds to and retains the androgen receptor (AR) in the nucleus by facilitating AR association with the nuclear zinc finger protein ZNHIT3. GAD65 knockdown decreased the growth of multiple established CRPC xenografts and markedly delayed the time to emergence of castration resistance. These data encourage exploring GAD65 as a therapeutic target for CRPC.

Significance:
This study reports metabolic alterations that could be responsible for the development of CRPC and identifies the GABA-producing enzyme GAD65 as a potential new therapeutic target.
See related commentary by Taylor and Watt, p. 4580
The EGFR Exon 19 Mutant L747-A750&gt;P Exhibits Distinct Sensitivity to Tyrosine Kinase Inhibitors in Lung Adenocarcinoma
Authors: Truini Anna , Starrett Jacqueline H. , Stewart Tyler , Ashtekar Kumar , Walther Zenta , Wurtz Anna , Lu David , Park Jin H. , DeVeaux Michelle , Song Xiaoling , Gettinger Scott , Zelterman Daniel , Lemmon Mark A. , Goldberg Sarah B. , Politi Katerina 
Published: June 2019

Abstract

Purpose:
EGFR exon 19 deletion (Ex19Del) mutations account for approximately 60% of lung cancer–associated EGFR mutations and include a heterogeneous group of mutations. Although they are associated with benefit from tyrosine kinase inhibitors (TKI), the relative inhibitor sensitivity of individual Ex19Del mutations is unknown.
Experimental Design: We studied the TKI sensitivity and structural features of common Ex19Del mutations and the consequences for patient outcomes on TKI treatment.

Results:
We found that the L747-A750&gt;P mutation, which represents about 4% of all Ex19Del mutations, displays unique inhibitor selectivity. L747-A750&gt;P differs from other Ex19Del mutations in not being suppressed completely by erlotinib or osimertinib, yet is completely inhibited by low doses of afatinib. The HCC4006 cell line (with the L747-A750&gt;P mutation) exhibited increased sensitivity to afatinib over erlotinib and osimertinib, and computational modeling suggests explanations for this sensitivity pattern. Clinically, patients with EGFR L747-A750&gt;P mutant tumors showed inferior outcomes when treated with erlotinib than patients with E746-A750 mutant tumors.

Conclusions:
These results highlight important differences between specific Ex19Del mutations that may be relevant for optimizing TKI choice for patients.
Spliced X-box Binding Protein 1 Stimulates Adaptive Growth Through Activation of mTOR
Authors: Wang Xiaoding , Deng Yingfeng , Zhang Guangyu , Li Chao , Ding Guanqiao , May Herman I. , Tran Diem H. , Luo Xiang , Jiang Ding-Sheng , Li Dan L. , Wei Xiang , Xu Lin , Ferdous Anwarul , Gillette Thomas G. , Scherer Philipp E. , Jiang Xuejun , Wang Zhao V. 
Published: June 2019

Background:
The unfolded protein response plays versatile roles in physiology and pathophysiology. Its connection to cell growth, however, remains elusive. Here, we sought to define the role of unfolded protein response in the regulation of cardiomyocyte growth in the heart.

Methods:
We used both gain- and loss-of-function approaches to genetically manipulate XBP1s (spliced X-box binding protein 1), the most conserved signaling branch of the unfolded protein response, in the heart. In addition, primary cardiomyocyte culture was used to address the role of XBP1s in cell growth in a cell-autonomous manner.

Results:
We found that XBP1s expression is reduced in both human and rodent cardiac tissues under heart failure. Furthermore, deficiency of XBP1s leads to decompensation and exacerbation of heart failure progression under pressure overload. On the other hand, cardiac-restricted overexpression of XBP1s prevents the development of cardiac dysfunction. Mechanistically, we found that XBP1s stimulates adaptive cardiac growth through activation of the mechanistic target of rapamycin signaling, which is mediated via FKBP11 (FK506-binding protein 11), a novel transcriptional target of XBP1s. Moreover, silencing of FKBP11 significantly diminishes XBP1s-induced mechanistic target of rapamycin activation and adaptive cell growth.

Conclusions:
Our results reveal a critical role of the XBP1s–FKBP11–mechanistic target of rapamycin axis in coupling of the unfolded protein response and cardiac cell growth regulation.
Recent Changes in Mean and Extreme Temperature and Precipitation in the Western Pacific Islands
Authors: McGree Simon , Herold Nicholas , Alexander Lisa , Schreider Sergei , Kuleshov Yuriy , Ene Elifaleti , Finaulahi Selu , Inape Kasis , Mackenzie Boyd , Malala Hans , Ngari Arona , Prakash Bipendra , Tahani Lloyd 
Published: June 2019

Abstract
Trends in mean and extreme annual and seasonal temperature and precipitation over the 1951–2015 period were calculated for 57 stations in 20 western Pacific Ocean island countries and territories. The extremes indices are those of the World Meteorological Organization Expert Team on Sector-Specific Climate Indices. The purpose of the expert team and indices is to promote the use of globally consistent climate indices to highlight variability and trends in climate extremes that are of particular interest to socioeconomic sectors and to help to characterize the climate sensitivity of various sectors. Prior to the calculation of the monthly means and indices, the data underwent quality control and homogeneity assessment. A rise in mean temperature occurred at most stations, in all seasons, and in both halves of the study period. The temperature indices also showed strong warming, which for the majority was strongest in December–February and weakest in June–August. The absolute and percentile-based indices show the greatest warming at the upper end of the distribution. While changes in precipitation were less consistent and trends were generally weak at most locations, declines in both total and extreme precipitation were found in southwestern French Polynesia and the southern subtropics. There was a decrease in moderate- to high-intensity precipitation events, especially those experienced over multiple days, in southwestern French Polynesia from December to February. Strong drying trends have also been identified in the low- to moderate-extreme indices in the June–August and September–November periods. These negative trends contributed to an increase in the magnitude of meteorological drought in both subregions.
Memories between Eras: ANFASEP’s Leaders before and after Peru’s Internal Armed Conflict
Authors: Crisóstomo Meza Mercedes 
Published: June 2019

During Peru’s internal armed conflict (1980–2000), many women formed associations of relatives of victims to demand truth, justice, and reparations. The Asociación Nacional de Familiares de Secuestrados, Detenidos y Desaparecidos del Perú (National Association of Relatives of the Kidnapped, Detained, and Disappeared of Peru—ANFASEP) was the first of these organizations. Accounts by its leaders of their early lives challenge the stereotypes of them employed in previous studies and point to changes in their senses of identity in the postconflict period. Their memories are part of the development of a self-narrative in which new rationales emerge and they are led to question the validity of the characterization of them as poor, illiterate, dependent women unaware of having rights. Durante el conflicto armado interno (1980–2000) muchas mujeres formaron asociaciones de familiares de víctimas para demandar verdad, justicia y reparación. En el Perú, ANFASEP fue la primera organización de este tipo. Este artículo presenta narraciones que las presidentas de esta asociación hacen sobre su infancia, matrimonio y maternidad. Por un lado, esto permite cuestionar las caracterizaciones y estereotipos que estudios previos han hecho sobre ellas. Y, por otro lado, aporta elementos teóricos sobre el cambio de sentidos de identidad en el post- conflicto. Desde una perspectiva cualitativa planteo que las memorias que las presidentas de ANFASEP elaboran sobre sus primeros ciclos de vida, recreadas o no, se inscriben en una narración y construcción de un auto-relato entre épocas. En este nuevo contexto, se producen nuevas lógicas de posicionamiento donde sus primeros ciclos de vida se tornan definitorios y desde donde se cuestionan los estereotipos que se han elaborado sobre ellas.
On-clamp versus off-clamp robotic partial nephrectomy: A systematic review and meta-analysis
Authors: Antonelli Alessandro , Veccia Alessandro , Francavilla Simone , Bertolo Riccardo , Bove Pierluigi , Hampton Lance J , Mari Andrea , Palumbo Carlotta , Simeone Claudio , Minervini Andrea , Autorino Riccardo 
Published: June 2019

Background: The debate on the pros and cons of robot-assisted partial nephrectomy performed with (on-clamp) or without (off-clamp) renal artery clamping is ongoing. The aim of this meta-analysis is to summarize the available evidence on the comparative studies assessing the outcomes of these two approaches. Material and methods: A systematic review of the literature on PubMed, ScienceDirect®, and Embase® was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses Statement (PRISMA). Only comparative and case-control studies were submitted to full-text assessment and meta-analysis. RevMan 5.3 software was used. Results: From the initial retrieval of 1937 studies, 15 fulfilling inclusion criteria were selected and provided 2075 patients for analysis (702 off-clamp, 1373 on-clamp). Baseline tumor’s features showed a significant difference in size (weighted mean difference: –0.58 cm; 95% confidence interval: [–1.06, –0.10]; p = 0.02) and R.E.N.A.L. score (weighted mean difference: –0.53; 95% confidence interval: [–0.81, –0.25]; p = 0.0002), but not in the exophytic property, the location, and the PADUA score. Pooled analysis revealed shorter operative time (p = 0.02) and higher estimated blood loss (p = 0.0002) for the off-clamp group. Overall complication and transfusion rates were similar, while higher major complication rate was observed in the on-clamp approach (5.6% vs 1.9%, p = 0.03). No differences in oncological outcomes were found. Finally, functional outcomes (assessed by estimated glomerular filtration rate at early postoperative, 3 month, 6 month, and last available follow-up) were not statistically different. Conclusion: This meta-analysis shows that off-clamp robot-assisted partial nephrectomy is reserved to smaller renal masses. Under such conditions, no differences with the on-clamp approach emerged.
Serum Lactate as an Independent Predictor of In-Hospital Mortality in Intensive Care Patients
Authors: Chebl Ralphe Bou , Tamim Hani , Dagher Gilbert Abou , Sadat Musharaf , Enezi Farhan Al , Arabi Yaseen M. 
Published: June 2019

Purpose: The aim of this study was to check if serum lactate was independently associated with mortality among critically ill patients. Materials and Methods: This was a single-center, retrospective cohort study. All adult patients (>18 years of age) who had at least 1 measurement of lactate within 24 hours of admission to intensive care unit (ICU) between January 2002 and December 2017 were included in the analysis. Patients were stratified into 3 groups: those with a serum lactate of <2 mmol/L (normal level), 2 to 4 mmol/L (intermediate level), and >4 mmol/L (high level). The primary outcome was in-hospital mortality. Secondary outcomes included ICU and hospital lengths of stay and mechanical ventilation duration. To determine the association between lactate level and hospital mortality, bivariate and multivariate logistic regression analyses were performed. Results: Of the 16,447 patients admitted to the ICU, 8167 (49.65%) had normal levels, 4648 (28.26%) had an intermediate, and 3632 (22.09%) had high lactate levels. Hospital mortality was the highest in high lactate level, followed by the intermediate and the normal level group (47.4% vs 26.5% vs 19.6%; P < .0001). Intermediate and high lactate levels were independent predictors of hospital mortality (odds ratio [OR], 1.32; 95% confidence interval [CI]: 1.20-1.46, and 1.94; 95% CI, 1.75-2.16, respectively) as well as ICU mortality (OR, 1.47; 95% CI, 1.30-1.66 and 2.56; 95% CI, 2.27-2.88, respectively). Conclusions: Intensive care unit serum lactate is associated with increased ICU and hospital mortality, independent of comorbidities, organ dysfunction, or hemodynamic status.
Male nursing students’ perception of dignity in neonatal intensive care units
Authors: Mohammadi Fateme , Oshvandi Khodayar , Med Hazel Kyle 
Published: June 2019

Introduction: Maintaining dignity is one of the most important human rights. However, maintaining and promoting the dignity of nursing students as an important caregiver group has scarcely been considered. Dignity can be viewed as an abstract concept particularly in relation to the perspective of male nursing student perspective. Therefore, more investigation is required to explore the male students’ understanding of the concept of dignity. Objectives: The purpose of this study is to define and explain the concept of dignity among male nursing students in the neonatal intensive care unit. Research design: This is a qualitative content analysis study. The data were collected through semi-structured individual interviews. The data were analyzed by conventional content analysis method. Participants and research context: Twenty male nursing students in public health centers in Iran were selected by targeted sampling to achieve data saturation between February 2017 and November 2017. Findings: The findings of this study were presented in three main themes, including “extensive support,” “belief in ability,” and “participation in decision making,” and 7 sub-categories of data were extracted. Ethical considerations: The study’s protocol was approved by the Research Ethics Committee of the Shiraz University of Medical Sciences and the ethical principles were followed throughout the study. Discussion and conclusion: According to the findings of the study, male nursing students required extensive support, and their academic and practical skills required to be respected; in addition, they should be involved in decision making, because in such an environment, the dignity of these students will be maintained and promoted. Therefore, it is suggested that a cultural, professional, and institutional background in which all components of the male nursing student’s dignity are protected and emphasized should be provided.