bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced risk of prostate cancer in a cohort of Lithuanian diabetes patients
Authors: Kincius Marius , Ausvydas Patasius , Donata Linkeviciute-Ulinskiene , Stukas Rimantas , Lina Zabuliene , Giedre Smailyte 
Published: November 2019

Abstract
Background: The aim of this study was to determine whether type 2 diabetes mellitus and treatment with metformin is associated with prostate cancer risk. Methods: Male patients with diagnosis of type 2 diabetes during the period of 2000 – 2016 were identified in the National Health Insurance Fund database. The prostate cancer cases were identified by pooling these records from the national Cancer Registry. The calculation of prostate cancer stardardized incidence ratios (SIRs) was composed as a ratio of observed number of cancer case in people with diagnosis of diabetes to the expected number of cancer cases in the underlying general population. Results: Overall, 64,000 males diagnosed with diabetes in Lithuania between 2000 and 2016 were included in the final cohort. 2,754 prostate cancers were observed versus 3,111.26 expected within the period of observation entailing an SIR of 0.89 (95% CI: 0.85–0.92). Significantly lower risk of prostate cancer was found in diabetes patients in all age groups, there were no differences in prostate cancer risk by time since diagnosis of diabetes. Significantly lower risk of prostate cancer also was found in both metformin users and never-users’ groups, with higher risk reduction in metformin users (SIR 0.71, 95% CI: 0.68–0.75) than in diabetes patients never-users (SIR 0.88, 95% CI: 0.80–0.96). Conclusions: In this large population-based study we found a significantly decreased risk of prostate cancer among men with diabetes and metformin users. However, the risk of prostate cancer showed no clear trend with diabetes duration and cumulative metformin dose.
A Prospective, Randomized, Placebo Controlled Study of a Combination of Simvastatin and Chemotherapy in Metastatic Breast Cancer
Authors: Alarfi Hiba , Youssef Lama , Salamoon Maher 
Published: November 2019

Abstract
Background: Preclinical studies support anticancer activity of statins, however, the existing clinical evidence are inconsistent and not definitive. Our study aimed at evaluating a postulated cancer chemo sensitizing effect of statin (simvastatin) in a cohort of metastatic breast cancer (MBC) patients.Methods: We designed a prospective, single-centered, randomized, double blinded, and placebo controlled trial that encompassed MBC patients with an ECOG Performance Status scale ≤2 and undergoing a chemotherapy course consisting of carboplatin and vinorelbine at Al-Baironi Hospital, Damascus, Syria. Patients were enrolled between August 2011 and July 2012, and randomly allocated to receive a 15-day course of either simvastatin (40 mg) or placebo at the day -7 of each chemotherapy cycle. Primary endpoints were objective response rate (ORR) and toxicity, and secondary endpoint was overall survival (OS).Results: Eighty-Two patients met the inclusion criteria and consented. ORR (35% vs. 32.5%) and predominant toxicity; grade≥3 neutropenia (occurred in 30% vs. 40% of the patients) were not significantly different between simvastatin and placebo groups, respectively. Over a median follow-up of 44 months (range, 10-60), median OS was 15 months in simvastatin group and 17 in placebo group (Hazard ratio (HR)=1.16, 95% CI (0.70-1.91), P =0.57). Elevated baseline values of high-sensitivity C-reactive protein (hsCRP >10 mg/l), lactate dehydrogenase (LDH >480 U/L) and chemotherapy being ≥2 nd line significantly associated with shorter OS for the total cohort in both univariate and multivariate analyses. Conclusions: Our data prove a safe profile of simvastatin at 40 mg per day combined with carboplatin and vinorelbine in MBC patients, but without any beneficial increase of tumor sensitivity to chemotherapy. Moreover, we demonstrated a strong clinical advantage of baseline values of hsCRP and LDH as useful prognostic tools in MBC patients. Trial registration: Damascus University / 15073/. Registered on December 28, 2010.
Metabolite and transcriptome analyses provide new insights into the generation of the blue supramolecular pigment in cornflower
Authors: Deng Chengyan , Wang Jiaying , Lu Chenfei , Li Yanfei , Hong Yan , Dai Silan 
Published: November 2019

Abstract
Background Generally, cyanidin facilitates pink to red petal colours, whereas it causes the expression of a vivid blue colour in cornflower. Previous chemical studies show that the pure blue colour in cornflower petals originates from a blue supramolecular pigment composed of cyanidins, apigenins and metal ions in a stoichiometric ratio, suggesting that the generation of this blue pigment complex is precisely regulated. However, the potential molecular mechanism remains unclear, restricting the innovation of blue cultivars in flowers originally accumulating cyanidin derivatives.Results In the present study, we traced the dynamic changes in petal colour from white to violet and, finally, to blue on the same petal in cornflower. Pigment analysis showed that apigenin biosynthesis started in the white region and peaked in the violet and blue regions, while cyanidin accumulated in the blue region to almost 2.5-fold higher than that in the violet region, suggesting that the content ratio of the two flavonoids plays a key role in blue colour development. Nine libraries from the above three colour regions were constructed for RNA-Seq, and 105,506 unigenes were obtained by de novo assembly. The differentially expressed genes among the three colour regions were significantly enriched in the phenylpropanoid biosynthesis and flavonoid biosynthesis pathways, leading to the excavation and analysis of 46 structural genes. Moreover, the R2R3-MYB and IIIf bHLH proteins were identified as cyanidin biosynthetic activators by both the dual luciferase reporter assay and transient over-expression in tobacco leaves. Moreover, eight differentially expressed unigenes possibly involved in metal ion transport, storage, tolerance and chelating processes were screened out.Conclusion The co-existence as well as the appropriate ratio of cyanidin and apigenin directly influence the blue colour development in cornflower. CcMYB6-1 and CcbHLH1 are identified as activators in regulating cyanidin biosynthesis and metal ion related gene resources that may be involved in chelating with flavonoids are also mined. These obtained results provide new insights into the generation of the blue supramolecular pigment in cornflower.
Effects of a nurse-led medication self-management programme in cancer patients: a mixed-method randomised controlled trial
Authors: Komatsu Hiroko , Yagasaki Kaori , Yamaguchi Takuhiro , Mori Ayako , Kawano Hiromi , Minamoto Noriko , Honma Orie , Tamura Kenji 
Published: November 2019

Abstract
Background : Despite patient convenience and better tolerability, treatment challenges have become evident compared with conventional chemotherapy. This study evaluated the effects of a patient-centred medication self-management support programme in patients with metastatic breast cancer undergoing oral anticancer treatment. We also evaluated the programme’s effectiveness based on the perceptions of intervention nurses.
Methods: This trial was a two-phased mixed-method approach, with a prospective randomised, parallel-group, two-arm, open-label, four-centre study, followed by a qualitative study using a focus-group interview. Eligible participants were 155 patients with metastatic breast cancer who had been newly prescribed an oral chemotherapy or a targeted therapy agent. The intervention group received the patient-centred medication self-management support programme conducted by trained nurses. Primary outcome was adherence to medication at three months after the commencement of oral chemotherapy or target therapy, calculated as Medication Possession Ratio (MPR). Patients were defined as being adherent if MPR was equal to or greater than 90%. Secondary outcomes included the Japanese version of the General Self-Efficacy (GSE) Scale, Functional Assessment of Cancer Therapy-Breast (FACT-B), Kessler 6 (K6), M.D. Anderson Symptom Inventory (symptom severity and symptom interference), and patient satisfaction score.
Results:
Primary outcome (MPR ≥ 0.9 at three months) was not significantly different in the intervention group (59/64 patients: 92%) and control group (54/59 patients: 92%). There was no significant difference in secondary outcomes except for GSE (p = 0.026). In the qualitative study, comments about the intervention programme of 20 participating nurses were positive. They also felt a patient’s enhanced self-efficacy by reassurance or endorsement.
Conclusions: The patient-centred medication self-management support programme in patients with metastatic breast cancer undergoing oral anticancer treatment did not improve medication adherence because the adherence rate was high in both groups. Nevertheless, this study offers suggestions to design future studies for optimal adherence to oral medication therapy, including focusing on patients with high risk of non-adherence and the effect of involvement of other healthcare providers.
Pulmonary microbiome patterns correlate with the course of the disease in patients with sepsis-induced ARDS
Authors: Schmitt Felix Carl Fabian , Lipinski Anna , Hofer Stefan , Uhle Florian , Nusshag Christian , Hackert Thilo , Dalpke Alexander H. , Weigand Markus A. , Brenner Thorsten , Boutin Sébastien 
Published: November 2019

Abstract
Background Patients with sepsis-induced Acute Respiratory Distress Syndrome (ARDS) are hallmarked by high mortality rates. An early and goal directed antibiotic therapy is crucial for patients’ survival. The clinical use of a Next Generation Sequencing (NGS)-based approach for pathogen identification might lead to an improved diagnostic performance. Therefore, the objective of this study was to examine changes in the pulmonary microbiome and resulting influences on patients’ outcome in septic ARDS, but also to compare NGS- and culture-based diagnostic methods for pathogen identification.Results In total, 30 patients in two groups were enrolled in the study: (1) 15 septic ARDS patients and (2) 15 patients undergoing oesophageal resection serving as controls. In the ARDS group, blood samples were collected at ARDS onset as well as 5 days and 10 days afterwards. At the same timepoints, bronchoalveolar lavages (BAL) were performed to collect epithelial lining fluid for culture-, as well as NGS-based analyses and to evaluate longitudinal changes in the pulmonary microbiome. In the control group, only one BAL and one blood sample were collected immediately prior to the surgical procedure. ARDS patients showed a significantly decreased α-diversity (p=0.003**) and an increased dominance (p=0.005**) in their pulmonary microbiome. The α-diversity index revealed a good correlation with the length of stay in the intensive care unit (ICU) (p-value=0.027) and the need for mechanical ventilation (p-value=0.027). In 42.9% of all ARDS patients, culture-based results were not concordant with NGS-based findings. Moreover, culture-based results remained negative in 5 cases where NGS-based diagnostics revealed signs of bacterial colonisation.Conclusion Sepsis-induced ARDS is associated with a significant dysbiosis of patients’ pulmonary microbiome, which is closely correlated with the clinical course of the disease. Furthermore, an NGS-based diagnostic approach was shown to be promising for pathogen identification in septic ARDS.
A Study on the Perimenopausal Symptoms and Its Relevant Factors
Authors: Liang Wenjing , Zhao Chongbang , Wang Xianglan , Guan Nianhong , Wang Jihui , Zhang Guican , Zhu Qi , Zhang Ming , Xu Sebao 
Published: November 2019

Abstract
Objective: To explore the relevant factors of perimenopausal symptoms. Method: Community female subjects conforming to perimenopausal criteria were recruited through advertising. Modified Kupperman Index(KI) was used for evaluation of perimenopausal symptoms, Zung Self-Rating Depression Scale (SDS)for depressive symptoms and Zung Self-Rating Anxiety Scale (SAS)for anxiety symptoms. Eysenck Personality Questionnaire(EPQ) is used to evaluate the individual mental characteristics of subjects,including Extraversion(E), Neuroticism (N),Psychoticism(P),and Lie(L). Metacognition Questionnaire-30 (MCQ-30) is used to evaluate the metacognitive levels of subjects in the 5 important factors, including cognitive confidence(F1), positive beliefs about worry(F2), cognitive self-consciousness(f3), negative beliefs about uncontrollability of thoughts and danger(F4), and beliefs about the need to control thoughts (F5). Meanwhile, the levels of plasma gonadal hormones such as diol, testosterone and progesterone, are monitored. Pairwise correlation and linear regression are used to analyze the relevance between perimenopausal symptoms and the aforementioned factors. Results: Among 66 perimenopausal female subjects, 40 (60.4%) showed perimenopausal symptoms, with the most frequent being fatigue, joint and muscle pain , headache, dizziness, hypersensitivity and agitation. N score(β’=0.419，P<0.001), SDS anxiety factor (β’=0.363，P<0.001)and BMI （β’=0.244，P=0.001） are significantly correlated with KI total score. Age（β’=0.482，P<0.001）, SDS anxiety factor（β’=0.276，P=0.006）, SDS core depressive factor（β’=0.287，P=0.010）and SDS anxiety factor（β’=0.287，P=0.010）are significantly correlated with psychological symptoms. SAS standard score (β’=0.277，P=0.029) and SDS (β’=0.254，P=0.045) are significantly correlated with somatic symptoms. Conclusion: Emotional symptoms such as depression and anxiety are apparent. Perimenopausal females with Neuroticism personality, of elder age and higher BMI suffer from perimenopausal symptoms more severely.
Characteristics of Psychiatric Patient's Use of One Emergency Department and Crisis Services and Comparison of Models of Care for Patients with Borderline Personality Disorder in the Frequency of Use of Emergency Services
Authors: Veluri Ramamohan , Roles Stacey , Heale Roberta , Nguyen Vicky P. K. H. , Renouf M. Elizabeth 
Published: November 2019

Abstract
Background: The cost of urgent mental health care services is high, both to the system as well as the individual and strategies that prevent these visits are paramount. Frequent users of the emergency department (ED) are a small percentage of ED patients but account for a large percent of visits. In particular, studies show that those patients with borderline personality disorder commonly present to urgent care. Given the rising number of ED visits and the corresponding cost to the health care system, it is important to explore strategies for avoidable or preventable visits to the ED, coupled with directing resources that ensure access to appropriate quality care. Methods: This research was a prospective chart review of the population of frequent users diagnosed with psychiatric illness in the (ED) and crisis (CRI) services at one hospital. Detailed analysis revealed characteristics of the patients who presented to the ED and CRI with a mental health diagnosis. Additional analysis of the subgroup of these patients with borderline personality disorder and/or self-harming behaviour was completed to determine the impact of the model of psychiatric care on subsequent crisis or ED visits in the year after the index visit. Results: The majority of patients presenting for mental health issues did so once. The mean number of subsequent presentations to the ED was 5.00 demonstrating that a small number of patients presented many times. Male patients were trending toward significance for number of ED and CRI visits. Patients with borderline personality disorder and/or self-harming behaviours in a model of care that offered increased access to services were less likely to visit the ED and CRI. Conclusions: Unstable or complex patients with psychiatric issues often present at the ED and CRI. Accessibility to community care services has the potential to reduce the number of ED and CRI visits and is a critical factor when considering this less stable group.
Equations of state, phase relations, and oxygen fugacity of the Ru-RuO2 buffer at high pressures and temperatures
Authors: Armstrong Katherine , Siersch Nicki C. , Boffa-Ballaran Tiziana , Frost Daniel J. , Yu Tony , Wang Yanbin 
Published: November 2019

Abstract
Experimental studies and measurements of inclusions in diamonds show that ferric iron components are increasingly stabilized with depth in the mantle. To determine the thermodynamic stability of such components, their concentration needs to be measured at known oxygen fugacities. The metal-oxide pair Ru and RuO2 are ideal as an internal oxygen fugacity buffer in high-pressure experiments. Both phases remain solid to high temperatures and react minimally with silicates, only exchanging oxygen. To calculate oxygen fugacities at high pressure and temperature, however, requires information on the phase relations and equation of state properties of the solid phases.
We have made in situ synchrotron X-ray diffraction measurements in a multi-anvil press on mixtures of Ru and RuO2 to 19.4 GPa and 1473 K with which we have determined phase relations of the RuO2 phases and derived thermal equations of state (EoS) parameters for both Ru and RuO2. Rutile-structured RuO2 was found to undergo two phase transformations, first at ~7 GPa to an orthorhombic structure and then above 12 GPa to a cubic structure. The phase boundary of the cubic phase was constrained for the first time at high pressure and temperature. We have derived a continuous Gibbs free energy expression for the tetragonal and orthorhombic phases of RuO2 by fitting the second-order phase transition boundary and P-V-T data for both phases, using a model based on Landau theory. The transition between the orthorhombic and cubic phases was then used along with EoS terms derived for both phases to determine a Gibbs free energy expression for the cubic phase. We have used these data to calculate the oxygen fugacity of the Ru + O2 = RuO2 equilibrium, which we have parameterized as a single polynomial across the stability fields of all three phases of RuO2. The expression is log10fO2(Ru – RuO2) = (7.782 – 0.00996P + 0.001932P2 – 3.76 × 10–5P3) + (–13 763 + 592P – 3.955P2)/T + (–1.05 × 106 – 4622P)/T2, which should be valid from room pressure up to 25 GPa and 773–2500 K, with an estimated uncertainty of 0.2 log units. Our calculated fO2 is shown to be up to 1 log unit lower than estimates that use previous expressions or ignore EoS terms.
A multi-model integration method for monthly streamflow prediction: modified stacking ensemble strategy
Authors: Li Yujie , Liang Zhongmin , Hu Yiming , Li Binquan , Xu Bin , Wang Dong 
Published: November 2019

Abstract
In this study, we evaluate elastic net regression (ENR), support vector regression (SVR), random forest (RF) and eXtreme Gradient Boosting (XGB) models and propose a modified multi-model integration method named a modified stacking ensemble strategy (MSES) for monthly streamflow forecasting. We apply the above methods to the Three Gorges Reservoir in the Yangtze River Basin, and the results show the following: (1) RF and XGB present better and more stable forecast performance than ENR and SVR. It can be concluded that the machine learning-based models have the potential for monthly streamflow forecasting. (2) The MSES can effectively reconstruct the original training data in the first layer and optimize the XGB model in the second layer, improving the forecast performance. We believe that the MSES is a computing framework worthy of development, with simple mathematical structure and low computational cost. (3) The forecast performance mainly depends on the size and distribution characteristics of the monthly streamflow sequence, which is still difficult to predict using only climate indices.
THE FIRST CASE OF HUMAN GENOME EDITING: CRIMINAL LAW PERSPECTIVE
Authors: Sergeev D. 
Published: November 2019

This article analyzes the legal assessment of the human genome modification experiment at the pre-implantation stage conducted by a group of scientists headed by He Jiankui, professor at the Southern University of Science and Technology (SUSTech) in Shenzhen, Guangdong Province, China, by means of the CRISPR/Cas9 technology. Chinese scholars have different opinions concerning He Jiankui’s experiment, but on the whole condemn it as illegal. Though CRISPR/Cas9 has been applied for quite a long time, the legislation of most developed countries is not ready to respond. The author of the article underlines the fact that despite the consolidated opinion of scholars, there is no binding international act which would restrict human genome editing. The author relies on Chinese sources in considering the main approaches to the assessment of He Jiankui’s actions in terms of criminal law (illegal medical activity, forgery of documents or fraud). Based on the analysis of Chinese criminal law doctrine, the author offers possible models of classifying separate actions related to human genome manipulation. The following cases of human genome manipulation are considered by the author as publicly dangerous and criminally liable: (a) when the embryo genome is changed by genetic engineering technologies for the purpose of its further implantation in the situation where the child’s parents are not aware of such intervention and its possible implications; (b) when genetic therapy or any other gene transfer (transgenesis) is applied to a person who is not aware of the nature of such manipulation and the possible implications of the application of the technology.
“BRICS LAW”: AN OXYMORON , OR FROM COO PERATION , VIA CON SOLIDATION , TO CODIFICATION?
Authors: Neuwirth R. 
Published: November 2019

In the global arena, the cooperation between the BRICS countries – Brazil, Russia, India, China and South Africa – covers around 42% of the world’s population and some of the world’s most dynamic emerging economies. Initially, the BRICS cooperation was suggested as an idea, and it was later welcomed as a new addition to the global governance debate about the future. The BRICS countries have already held ten consecutive summits of heads of state plus a large number of meetings at the ministerial level. The cooperation describes itself as a “cooperation and dialogue” platform, but it has nonetheless signed a number of binding treaties and, notably, established the New Development Bank (NDB) as a permanent institution headquartered in Shanghai (China).The cooperation has also met with resistance, criticism and problems caused by the overall complexity of global affairs in a rapidly changing world. The diversity and remote locations of the BRICS countries have also been thought of as an obstacle to their successful cooperation and their ability to play an active part in global governance in the twentyfirst century. The main challenge thus lies in their ability to overcome their differences and to make a difference in designing the future global political and economic world order. Against the backdrop of the global governance debate, the present paper therefore asks whether the BRICS cooperation constitutes a novel model of regionalism with multilateral aspirations, and what role law and, notably, the “rule of law” can play in this important task. The paper includes a discussion of the extent to which the BRICS cooperation needs to be upgraded in legal and institutional terms, and possibly to proceed from cooperation via consolidation to the codification of its most important sources of global law.