bluuebunny/crossref_metadata_2025_split huggingface dataset:
Postoperative radiotherapy for pathological stageIIIA‐N2 non‐smallcell lung cancer with positive surgical margins
Authors: Yuan Meng , Men Yu , Kang Jingjing , Sun Xin , Zhao Maoyuan , Bao Yongxing , Yang Xu , Sun Shuang , Ma Zeliang , Wang Jianyang , Deng Lei , Wang Wenqing , Zhai Yirui , Liu Wenyang , Zhang Tao , Wang Xin , Bi Nan , Lv Jima , Liang Jun , Feng Qinfu , Chen Dongfu , Xiao Zefen , Zhou Zongmei , Wang Luhua , Hui Zhouguang 
Published: November 2020

BackgroundThe aim of this study was to evaluate the efficacy of postoperative radiotherapy (PORT) in stage pIIIA‐N2 non‐small cell lung cancer (NSCLC) patients with positive surgical margins.MethodsBetween January 2003 and December 2015, patients who had undergone lobectomy or pneumonectomy plus mediastinal lymph node dissection or systematic sampling in our single institution were retrospectively reviewed. Those with pIIIA‐N2 NSCLC and positive surgical margins were enrolled into the study. The Kaplan‐Meier method was used for survival analysis, and the log‐rank test was used to analyze differences between the groups. Univariate and multivariate analyses using Cox proportional hazards regression models were performed to evaluate potential prognostic factors for OS. Statistically significant difference was set asP < 0.05.ResultsOf all the 1547 patients with pIIIA‐N2 NSCLC reviewed, 113 patients had positive surgical margins, including 76 patients with R1 resection and 37 with R2 resection. The median overall survival (OS) was 28.3 months in the PORT group and 22.6 months in the non‐PORT group (P= 0.568). Subset analysis showed that for patients with R1 resection, the median OS was 52.4 months in the PORT group which was nonsignificantly longer than that of 22.6 months in the non‐PORT group (P= 0.127), whereas PORT combined with chemotherapy could significantly improve OS, with a median OS of 52.4 months versus 17.2 months (P= 0.027). For patients with R2 resection, PORT made no significant difference in OS (17.6 vs. 63.8 months,P= 0.529).ConclusionsFor pIIIA‐N2 NSCLC patients with positive surgical margins, PORT did not improve OS, but OS was improved in those patients who underwent R1 resection combined with chemotherapy.Key pointsSignificant findings of the studySignificant findings of the study: Postoperative radiotherapy (PORT) has been recommended to treat patients with positive surgical margins. However, the existing evidence is controversial and high‐level evidence is lacking.What this study addsWhat this study adds: The PORT group had markedly, but not statistically significant, longer median OS compared with the non‐PORT group in patients with R1 resection. OS was significantly longer in the patients with R1 resection receiving adjuvant CRT than the surgery alone group.
Do National and International Ethics Documents Accord With the Consent Substitute Model for Emergency Research?
Authors: Langlois Adèle , Armstrong Stephanie , Siriwardena Aloysius Niroshan 
Published: November 2020

AbstractIn 2010 Largent, Wendler, and Emanuel proposed the “consent substitute model” for emergency research with incapacitated participants. The model provides a means to enroll participants in emergency research without consent, if five conditions are met: 1) the research addresses the patients’ urgent medical needs, 2) the risk–benefit ratio is favorable, 3) there are no known conflicts with patients’ values or interests, 4) cumulative net risk is minimal, and 5) consent is given as soon as possible. We review national and international ethics laws, regulations, and guidelines to determine 1) whether they accord with the consent substitute model’s five conditions and 2) the level of congruence across these documents. We find that only one document meets all five conditions and that there is significant disparity among the documents, particularly between national and international ones. These differences may have stymied international collaboration in emergency research. We recommend that the two international documents used most, the International Council for Harmonization’s Guideline for Good Clinical Practice and the World Medical Association’s Declaration of Helsinki, are revised to include more specific provisions on emergency medical research.
Five‐year mortality of severely malnourished patients with chronic anorexia nervosa admitted to a medical unit
Authors: Guinhut Marie , Godart Nathalie , Benadjaoud Mohamed‐Amine , Melchior Jean‐Claude , Hanachi Mouna 
Published: November 2020

AbstractObjectiveAnorexia nervosa (AN) is associated with one of the highest mortality rates of any psychiatric disorder but limited mortality data were reported for those with extremely severe malnutrition. This study aimed to estimate standardized mortality ratio (SMR), investigate predictive factors of mortality and causes of death among a sample of patients with AN admitted to a specialized clinical nutrition unit (CNU) because of extremely severe malnutrition.MethodsBetween 11/27/1997 and 01/15/2014, vital status was determined for 384 patients admitted for AN at the first time in the CNU. Sociodemographic, anamnestic, and clinical data were collected. We calculated the SMR. Univariate and multivariate Cox regression analyses were performed to identify mortality predictors.ResultsCrude mortality rate was 11.5%. (44 deaths) and SMR 15.9 [CI 95% (11.6–21.4)], 5.2 years post inpatient treatment. Mortality predictors at the time of hospitalization were as follows: older age, occurrence of an in‐hospital suicide attempt, transfer to medical intensive care unit and the following somatic complications: frank anemia, dysnatremia, infectious and cardiac complications. Other predictors of mortality were: past or present history of discharge against medical advice, hematological comorbidities (not related to AN). A longer inpatient length of stay was a protective factor.ConclusionVery severely malnourished patients with AN hospitalized in a medical unit because of extremely severe somatic issues have a medium‐term mortality rate higher than the general population and even higher than patients in tertiary specialized ED units. This study highlights predictive factors of mortality that will help clinicians in recognizing and managing patients at risk of death.
Canal transportation using Mani GPR or HyFlex NT during the retreatment of curved root canals: A micro‐computed tomographic study
Authors: Gomes Isabelle Luise Lima , Alves Flávio Rodrigues Ferreira , Marceliano‐Alves Marília F. , Silveira Stephanie B. , Provenzano José Claudio , Gonçalves Lucio Souza 
Published: November 2020

AbstractThis study assessed the apical transportation using Mani GPR or HyFlex NT during the retreatment of curved root canals. Thirty‐eight roots were analysed using micro‐CT for the comparison of apical transportation produced by two retreatment systems. Longitudinal transportation, horizontal transportation, variation in the canal angle of curvature and variation in the canal/root width ratio were analysed. Longitudinal transportation was frequently observed, regardless of the system used. The canals retreated with Mani GPR showed a significantly higher horizontal transportation at 1 mm from the root apex (P < 0.01) and greater variation of the canal curvature angle (P < 0.01). The canal/root width ratio was similar between groups (P > 0.05). In conclusion, longitudinal transportation occurred more frequently in the mesial canal walls. Mani GPR showed greater horizontal transportation at 1 mm short of the apex, and higher variation of the canal curvature angle compared with HyFlex NT.
Prevalence of potentially inappropriate prescribing in older adults in Jordan: Application of the STOPP criteria
Authors: Abu Hammour Khawla , Abdel jalil Mariam , AlHabeis Sara , Abu Hammour Ghayda' , Manaseer Qusai 
Published: November 2020

AbstractObjectivesTo measure the prevalence of cases of potentially inappropriate prescribing (PIP) for older patients and to identify the risk factors for identified cases of PIP.MethodsSTOPP criteria version 2 were used for identifying cases of PIP for older patients (>65 years) who were admitted to a tertiary hospital in Jordan over a period of 18 months. Data were collected by prospectively reviewing the clinical and prescription records of included patients. Descriptive analysis, univariate analysis and multiple linear regression were used to analyse the results.ResultsUpon admission, during hospitalisation and on discharge, 144, 182 and 156 cases of PIP were identified, respectively. There was a statistically significant association between the number of prescribed medications and cases of PIP during the hospital journey (P < .05).ConclusionInappropriate prescribing of medications is highly prevalent among older patients. Application of validated (STOPP) criteria can help to detect and direct development of interventions to prevent PIP occurrence among older patients.
Serum levels of soluble Fas and Fas ligand in pregnant women who smoke
Authors: Hasan Sean , Alshaikh Belal , Yusuf Kamran 
Published: November 2020

AbstractProblemCigarette smoking during pregnancy is associated with reduced incidence of preeclampsia. Mechanisms of this association are poorly understood. Cytokines, angiogenic, and anti‐angiogenic factors are involved in the pathogenesis of preeclampsia. During normal pregnancy, Fas ligand (FasL) present on trophoblasts induces apoptosis of Fas bearing maternal immune cells. In preeclampsia, trophoblasts show increased apoptosis with reduced expression of FasL. We determined serum levels of cytokines, angiogenic (placental growth factor), anti‐angiogenic factors (soluble endoglin, soluble fms‐like tyrosine kinase‐1), soluble Fas (sFas), and soluble FasL (sFasL) in smoking and non‐smoking pregnant women.MethodsUsing enzyme‐linked immunosorbent and multiplex assays, we prospectively analyzed serum levels of angiogenic, anti‐angiogenic factors, cytokines, sFas and sFasL in normotensive smoking and non‐smoking mothers. Exclusion criteria included maternal hypertension, auto‐immune disorders, rupture of membranes, evidence of labor, and drug use.ResultsOf 100 women recruited to the study, 51 were in the non‐smoking and 49 in the smoking group. Except for lower maternal age in the smoking group, there was no difference in gestation, BMI, gravidity, or ethnicity between the two groups. Levels of angiogenic, anti‐angiogenic factors, cytokines, and sFas were similar between the two groups but sFasL levels were significantly higher in smoking group (38 pg/ml vs. 16 pg/ml, p < .001) and remained significant after controlling for confounders.ConclusionOur study demonstrates higher sFasL levels in pregnant women who smoke. Higher sFasL may explain the reduced incidence of preeclampsia in pregnant mothers who smoke by inducing apoptosis of immune cells which may otherwise induce trophoblast apoptosis.
Oral berotralstat for the prophylaxis of hereditary angioedema attacks in patients in Japan: A phase 3 randomized trial
Authors: Ohsawa Isao , Honda Daisuke , Suzuki Yusuke , Fukuda Tomoo , Kohga Keisuke , Morita Eishin , Moriwaki Shinichi , Ishikawa Osamu , Sasaki Yoshihiro , Tago Masaki , Chittick Greg , Cornpropst Melanie , Murray Sharon C. , Dobo Sylvia M. , Nagy Eniko , Van Dyke Sharon , Reese Lacy , Best Jessica M. , Iocca Heather , Collis Phil , Sheridan William P. , Hide Michihiro 
Published: November 2020

AbstractBackgroundWith no approved treatments in Japan for the prevention of hereditary angioedema (HAE) attacks, there is a significant unmet need for long‐term prophylactic therapies for Japanese patients with HAE. Berotralstat (BCX7353) is an oral, once‐daily, highly selective inhibitor of plasma kallikrein in development for prophylaxis of angioedema attacks in HAE patients.MethodsAPeX‐J is a phase 3, randomized, double‐blind, placebo‐controlled, parallel‐group, 3‐part trial conducted in Japan (University Hospital Medical Information Network identifier, UMIN000034869; ClinicalTrials.gov identifier, NCT03873116). Patients with a clinical diagnosis of type 1 or 2 HAE underwent a prospective run‐in period of 56 days to determine eligibility, allowing enrollment of those with ≥2 expert‐confirmed angioedema attacks. Patients were randomly assigned (1:1:1) and stratified by baseline attack rate (≥2 vs. <2 expert‐confirmed attacks/month between screening and randomization) to receive once‐daily berotralstat 110 mg, berotralstat 150 mg, or placebo. The primary endpoint was the rate of expert‐confirmed angioedema attacks during dosing in the 24‐week treatment period.ResultsNineteen patients were randomized to receive once‐daily berotralstat 110 mg (n = 6), berotralstat 150 mg (n = 7), or placebo (n = 6). Treatment with berotralstat 150 mg significantly reduced HAE attacks relative to placebo (1.11 vs. 2.18 attacks/month, p = .003). The most frequently reported treatment‐emergent adverse events (TEAEs) in berotralstat‐treated patients (n = 13) were nasopharyngitis (n = 4, 31%), abdominal pain, cough, diarrhea, and pyrexia (n = 2 each, 15%).ConclusionsOrally administered, once‐daily berotralstat 150 mg significantly reduced the frequency of HAE attacks and was safe and well tolerated, supporting its use as a prophylactic therapy in patients with type 1 or 2 HAE in Japan.
Maternal N‐acetyl‐cysteine prevents neonatal brain injury associated with necrotizing enterocolitis in a rat model
Authors: Zmora Osnat , Gutzeit Ola , Segal Linoy , Boulos Sari , Millo Zvika , Ginsberg Yuval , Khatib Nizar , Fainaru Ofer , Ross Michael G. , Weiner Zeev , Beloosesky Ron 
Published: November 2020

AbstractIntroductionPreterm infants with necrotizing enterocolitis (NEC) are at increased risk of cerebral injury and neurodevelopmental dysfunction. N‐acetyl‐cysteine (NAC) is a known anti‐inflammatory and antioxidant agent. Currently, there is no prophylactic treatment in clinical use to prevent NEC and its neurodevelopmental sequelae. We sought to determine whether brain inflammation/apoptosis accompanies NEC systemic inflammation, and whether it can be attenuated by maternal NAC treatment during pregnancy and/or in the neonatal period in a rat model.Material and methodsAn established NEC newborn model (hypoxia 5% O2 for 10 min and formula feeding thrice daily, beginning on day 1 for 4 days) was used in Sprague‐Dawley rat pups (n = 32). An additional group of pups (n = 33) received NAC (300 mg/kg intraperitoneal thrice daily) in addition to NEC conditions (NEC‐NAC). Control pups (n = 33) were nursed and remained with the dam in room air. Two additional groups included pups of dams treated once daily with NAC (300 mg/kg intravenous) in the last 3 days of pregnancy. After birth, pups were randomized into NAC‐NEC (n = 33) with NEC conditions and NAC‐NEC‐NAC (n = 36) with additional postnatal NAC treatment. Pups were sacrificed on the fifth day of life. Pup serum interleukin (IL)‐6 protein levels, and brain nuclear factor kappa B (NF‐κB) p65, neuronal nitric oxide synthase (nNOS), Caspase 3, tumor necrosis factor alpha (TNF‐α), IL‐6 and IL‐1β protein levels were determined by ELISA, western blot and TUNEL staining, and the groups were compared using analysis of variance (ANOVA).ResultsNEC pups had significantly increased serum IL‐6 levels compared with the control group as well as increased neuronal apoptosis and brain protein levels of NF‐κB, nNOS, Caspase 3, TNF‐α, IL‐6 and IL‐1β compared with control. In all NAC treatment groups, levels of serum IL‐6, neuronal apoptosis and brain NF‐κB, nNOS, Caspase 3, TNF‐α, IL‐6 and IL‐1β protein levels were significantly reduced compared with the NEC group. The most pronounced decrease was demonstrated within the NAC‐NEC‐NAC group.ConclusionsNAC treatment can attenuate newborn inflammatory response syndrome and decrease offspring brain neuroapoptosis and inflammation in a rat model of NEC by inhibition of NF‐κB, nNOS and Caspase 3 pathways.
National Current Care Guidelines for paediatric lower respiratory tract infections reduced the use of chest radiographs but local variations were observed
Authors: Poutanen Roope , Virta Tuija , Heikkilä Paula , Pauniaho Satu‐Liisa , Csonka Peter , Korppi Matti , Renko Marjo , Palmu Sauli 
Published: November 2020

AbstractAimOur aim was to evaluate the impact of the 2014 Finnish Current Care Guidelines for paediatric lower respiratory tract infections (LRTIs), particularly on taking of chest radiographs.MethodsThis study used official national data and regional (Pirkanmaa) data on children aged 0‐16 years who underwent chest radiographs in 2011 and 2015. We also collected data for LRTI diagnoses from local registers, including prescribed antibiotics and taking of chest radiographs. The local cohort comprised children aged 0‐15 who presented to the primary care emergency room or to the hospital emergency department (Tampere university hospital) in November‐December 2012‐2015.ResultsChest radiographs for Finnish children aged 0‐16 fell from 2011 to 2015: by 15.9% nationally and by 16.9% in Pirkanmaa. When asylum seekers with chest radiographs for tuberculosis screening were excluded, the estimated national reduction was 29.9%. In the local cohort, chest radiographs increased from 82 to 139 (69.5%) between 2012/2013 and 2014/2015 as the occurrence of community‐acquired pneumonia (CAP) increased. However, the proportion of patients with CAP who had chest radiograph taken tended to decrease from 84.6% to 71.3% (p = 0.078).ConclusionDecreases in national and regional chest imaging trends were observed after the 2014 guidance for children`s LRTI was introduced.
Fit for addressing grand challenges? A process model for effective accountability relationships within multi‐stakeholder initiatives in developing countries
Authors: Hennchen Esther , Schrempf‐Stirling Judith 
Published: November 2020

AbstractBusiness is expected to contribute to grand challenges (GC) such as poverty within their corporate social responsibilities. Multi‐stakeholder initiatives (MSIs) have developed to a popular governance model to address GC. While existing scholarship has discussed the positive and negative aspects of MSIs, we know relatively little about how corporations within MSIs are held accountable. The objective of the study is to analyze the dynamics of accountability relationships between the corporate actor and the accountability forum to conceive a process model for effective accountability relationships in developing countries. We conducted an inductive study which explored the tensions the accountability forum perceives in MSI accountability relationships and the criteria to meet the forum's accountability claims. Our study identified four accountability criteria: transparency, inclusion, procedural fairness, and efficacy. Our main theoretical claim is that considering the four accountability criteria in the process of facilitating, dialoguing, and evaluating allows affected stakeholders to validate and match legitimacy claims with their own expectations, and thus, manage MSIs more effectively. Our contribution to existing scholarship on MSIs in developing countries is that we offer a novel perspective on analyzing the effectiveness of MSIs to address GC through our focus on one element of MSIs––specifically accountability. Beyond academic theorizing, this perspective may well hold value for nongovernmental organizations, policymakers, and business managers as it advances a concept of responsibility based on a set of accountability criteria which have the potential to become a cornerstone for how MSI members can organize to effectively address GC in developing countries.
Distinct circular RNA expression profiles in pediatric ependymomas
Authors: Ahmadov Ulvi , Bendikas Meile M. , Ebbesen Karoline K. , Sehested Astrid M. , Kjems Jørgen , Broholm Helle , Kristensen Lasse S. 
Published: November 2020

AbstractPediatric ependymomas frequently develop in the cerebellum and are currently treated using non‐specific therapies, in part, because few somatically mutated driver genes are present, and the underlying pathobiology is poorly described. Circular RNAs (circRNAs) constitute as a large class of primarily non‐coding RNAs with important roles in tumorigenesis, but they have not been described in pediatric ependymomas. To advance our molecular understanding of ependymomas, we performed Next Generation Sequencing of rRNA‐depleted total RNA of 10 primary ependymoma and three control samples. CircRNA expression patterns were correlated to disease stage, outcome, age, and gender. We found a profound global downregulation of circRNAs in ependymoma relative to control samples. Many differentially expressed circRNAs were discovered and circSMARCA5 and circ‐FBXW7, which are described as tumor suppressors in glioma and glioblastomas in adults, were among the most downregulated. Moreover, patients with a dismal outcome clustered separately from patients with a good prognosis in unsupervised hierarchical cluster analyses. Next, NanoString nCounter experiments were performed, using a custom‐designed panel targeting 66 selected circRNAs, on a larger cohort that also included medulloblastomas and pilocytic astrocytomas. These experiments indicated that circRNA expression profiles are different among distinct pediatric brain tumor subtypes. In particular, circRNAs derived from RMST, LRBA, WDR78, DRC1 and BBS9 genes were specifically upregulated in ependymomas. In conclusion, circRNAs have different expression profiles in ependymomas relative to controls and between survivors and patients with a dismal outcome, suggesting that circRNAs could be exerted as diagnostic and prognostic biomarkers in the future if further validated in larger cohorts.
Activation of trace amine‐associated receptor 1 selectively attenuates the reinforcing effects of morphine
Authors: Liu Jianfeng , Seaman Robert , Johnson Bernard , Wu Ruyan , Vu Jimmy , Tian Jingwei , Zhang Yanan , Li Jun‐Xu 
Published: November 2020

Background and PurposeTrace amine‐associated TA1 receptors play critical roles in regulating dopamine transmission. Previous studies showed that pharmacologically or genetically manipulating the activity of TA1 receptors modulates addiction‐like behaviours associated with psychostimulants. However, little is known about whether TA1 receptor modulation would regulate the behavioural effects of opioids.Experimental ApproachEffects of the selective TA1 receptor partial agonist RO5263397 on the addiction‐related and antinociceptive effects of morphine were systematically assessed in male rats and mice.Key ResultsRO5263397 attenuated the expression of morphine‐induced behavioural sensitization in wildtype but not TA1 receptor knockout mice. RO5263397 shifted the dose‐effect curve of morphine self‐administration downward and reduced the breakpoint in a progressive ratio schedule of reinforcement but did not affect food self‐administration in rats. RO5263397 decreased the cue‐ and drug‐induced reinstatement of morphine‐seeking behaviour in rats. RO5263397 alone did not trigger reinstatement of morphine‐seeking behaviour or change locomotor activity in rats with a history of morphine self‐administration. However, RO5263397 did not affect the expression of morphine‐induced conditioned place preference in mice or rats. RO5263397 did not affect naltrexone‐precipitated jumping behaviour or naltrexone‐induced conditioned place aversion in morphine‐dependent mice. Furthermore, RO5263397 did not affect the analgesic effects of morphine in an acute nociception model in mice and a chronic pain model in rats.Conclusion and ImplicationsThese results indicated that TA1 receptor activation selectively attenuated the reinforcing, but not withdrawal or antinociceptive effects of morphine, suggesting that selective TA1 receptor agonists might be useful to combat opioid addiction, while sparing the analgesic effects.