bluuebunny/crossref_metadata_2025_split huggingface dataset:
Calcium Intake and Survival after Colorectal Cancer Diagnosis
Authors: Yang Wanshui , Ma Yanan , Smith-Warner Stephanie , Song Mingyang , Wu Kana , Wang Molin , Chan Andrew T. , Ogino Shuji , Fuchs Charles S. , Poylin Vitaliy , Ng Kimmie , Meyerhardt Jeffrey A. , Giovannucci Edward L. , Zhang Xuehong 
Published: December 2018

Abstract

Purpose:
Although evidence suggests an inverse association between calcium intake and colorectal cancer incidence, the influence of calcium on survival after colorectal cancer diagnosis remains unclear.
Experimental Design: We prospectively assessed the association of postdiagnostic calcium intake with colorectal cancer–specific and overall mortality among 1,660 nonmetastatic colorectal cancer patients within the Nurses' Health Study and the Health Professionals Follow-up Study. Patients completed a validated food frequency questionnaire between 6 months and 4 years after diagnosis and were followed up for death. Multivariable hazard ratios (HRs) and 95% confidence intervals (95% CI) were calculated using Cox proportional hazards regression.

Results:
Comparing the highest with the lowest quartile intake of postdiagnostic total calcium, the multivariable HRs were 0.56 (95% CI, 0.32–0.96; P trend = 0.04) for colorectal cancer–specific mortality and 0.80 (95% CI, 0.59–1.09; P trend = 0.11) for all-cause mortality. Postdiagnostic supplemental calcium intake was also inversely associated with colorectal cancer–specific mortality (HR, 0.67; 95% CI, 0.42–1.06; P trend = 0.047) and all-cause mortality (HR, 0.71; 95% CI, 0.54–0.94; P trend = 0.008), although these inverse associations were primarily observed in women. In addition, calcium from diet or dairy sources was associated with lower risk in men.

Conclusions:
Higher calcium intake after the diagnosis may be associated with a lower risk of death among patients with colorectal cancer. If confirmed, these findings may provide support for the nutritional recommendations of maintaining sufficient calcium intake among colorectal cancer survivors.
An Illustrated Genealogy between the Ottomans and the Safavids
Authors: Taner Melis 
Published: December 2018

Abstract
This paper focuses on an early seventeenth-century illustrated genealogy (Museum of Ethnography Ankara, No. 8457), which is stylistically attributable to Baghdad, and is iconographically and textually pro-Safavid at a point when Baghdad was under Ottoman rule. Taking the format of the illustrated genealogy, which was widespread in the Otto­man realm from the mid-sixteenth century onwards, the Ankara manuscript adapts the Ottoman genealogical tree tradition with a particularly Safavid tenor. In its immediate visual graspability and use of the genealogy as a methodological tool to claim legitimacy, this manuscript represents contested identities in the frontier province of Baghdad.
Submarine Cables and Pipelines: The Protection of Investors Under International Law
Authors: Karavias Markos 
Published: December 2018

Abstract
Submarine cables and pipelines hold great significance for the global economy, as they constitute key features in energy transit and transmission of telecommunications data. Whereas the two have traditionally been treated by scholars through the lens of the international law of the sea, far less attention has been paid to the potential applicability of international investment law in this field. The present article seeks to shed light on this latter question. First, it reviews the most common treaty and contractual arrangements in place vis-à-vis submarine cables and pipelines. It then turns to international investment law with a view to examining whether investment treaties have a say on the protection of investors in the laying of submarine cables and the construction and operation of submarine pipelines. One of the more vexed questions in this respect is the territorial scope of investment law, in particular as regards the seabed beyond national jurisdiction.
A revision of taxonomic relation between Oenothera perangusta and O. ersteinensis (Onagraceae) based on morphometric research and statistical analyses
Authors: WOŹNIAK-CHODACKA MONIKA 
Published: December 2018

The taxonomic status of Oenothera ersteinensis and O. perangusta (sect. Oenothera, subsect. Oenothera; Onagraceae) has remained unresolved. According to the representatives of the so-called American school of taxonomy both names should be assigned, as their synonyms, to two separate, widely treated species (O. biennis and O. oakesiana, respectively) whereas European researchers consider both taxa as very similar or even as a single species. In order to establish the taxonomic relation between these taxa, detailed morphometric research and statistical analyses—principal component analysis, correspondence analysis, discriminant analysis and Wald-Wolfowitz runs test—were performed. As a background to present the differentiation between the considered taxa, analyses of European representatives of two distinct and widely distributed species, O. biennis and O. oakesiana, were also conducted. The results revealed that the highest discriminatory power have mostly qualitative features. Oenothera ersteinensis turned out to be a distinct and well-separated species belonging to the series Oenothera whereas O. perangusta is most probably only a synonym name of O. oakesiana. Moreover, it was demonstrated that all the investigated specimens labelled as O. perangusta were in fact misrecognized representatives of O. ersteinensis. The updated map of distribution of O. ersteinensis is also provided.
Global Stokes Drift Climate under the RCP8.5 Scenario
Authors: Breivik Øyvind , Carrasco Ana , Staneva Joanna , Behrens Arno , Semedo Alvaro , Bidlot Jean-Raymond , Aarnes Ole Johan 
Published: December 2018

AbstractThe future Stokes drift climate is investigated using a global wave climate projection (2071–2100) forced with EC-EARTH winds under the RCP8.5 scenario. The future climate run is compared against a historical run (1976–2005). The Stokes drift climate is analyzed in terms of Stokes transport and surface Stokes drift. The impact on Stokes drift from changes to the wind, wind sea, and swell climate is identified. The consequences for upper-ocean mixing and circulation are studied by investigating the turbulent Langmuir number and the Stokes depth. The historical climate run is also compared to a hindcast with ERA-Interim forcing. Systematic discrepancies due to differences in resolution and model physics are identified, but no fundamental weaknesses are uncovered that should adversely affect the future run. As the surface Stokes drift is largely dictated by high-frequency waves, it is to a great degree controlled by changes to the local wind field, whereas the Stokes transport is more sensitive to swell. Both are expected to increase in the Southern Ocean by about 15%, while the North Atlantic sees a decrease of about 10%. The Stokes depth and the turbulent Langmuir number are set to change by about ±20% and ±10%, respectively. The changes to the Stokes depth suggest a deeper impact of the Coriolis–Stokes force in the Southern Ocean and a decrease in the northern extratropics. Changes to the KPP Langmuir-enhancement factor suggests potentially increased mixing in the Southern Ocean and a reduction in the North Atlantic and the North Pacific.
Intermittent blockade of OGFr and treatment of autoimmune disorders
Authors: Zagon Ian S , McLaughlin Patricia J 
Published: December 2018

The opioid growth factor (OGF)–OGF receptor (OGFr) axis is present in normal and abnormal cells and tissues, and functions to maintain homeostatic cell replication. OGF is an inhibitory growth factor that upregulates p16 and/or p21 cyclin-dependent inhibitory kinases to slow cell replication. Blockade of this regulatory pathway can be intermittent or complete with the end result being depressed or accelerated, respectively, cell proliferation and growth. Intermittent blockade of the OGF–OGFr pathway with lose doses of naltrexone (LDN), a general opioid receptor antagonist, has been studied clinically in a number of autoimmune diseases, including fibromyalgia, Crohn’s, and multiple sclerosis (MS). Serum enkephalin levels were decreased in patients with MS relative to subjects with other neurological disorders. The intermittent blockade of OGFr by LDN results in a biofeedback mechanism that upregulates serum enkephalin levels. Clinical studies have reported that LDN is beneficial in enhancing quality of life, reducing fatigue, and increasing motor activity in humans with fibromyalgia, Crohn’s, or MS. LDN treatment is well tolerated even after several years of therapy. Preclinical investigations using experimental autoimmune encephalomyelitis (EAE), an animal model of MS mediated by T and B lymphocyte activation, demonstrate that immunization alone resulted in reduced enkephalin (i.e. OGF) levels. Therapy with LDN restored serum enkephalin levels in EAE mice resulting in improved EAE behavioral scores and diminished CNS pathology. This mini-review summarizes both preclinical and clinical data and focuses on the role of serum enkephalins resulting from intermittent blockade of OGFr by LDN in autoimmune disorders.Impact statementThis mini-review presents information on the intermittent blockade of the opioid growth factor (OGF)–OGF receptor (OGFr) axis by low-dose naltrexone (LDN), and the role of enkephalin (i.e. OGF) in autoimmune disorders, specifically multiple sclerosis, Crohn’s, and fibromyalgia. Clinical reports on subjects taking LDN have documented reduced fatigue, few side-effects, and improved overall health. Preclinical studies on mice with experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis, revealed that immunization for EAE reduces serum OGF. Intermittent OGFr blockade with LDN restores serum enkephalin levels that correlate with reduced behavioral and pathological signs of EAE; LDN also increases enkephalin levels in naïve mice. The interplay between LDN, and the onset and treatment of autoimmune diseases, chronic pain, and other addictive behaviors requires further investigation, but highlights a central role for enkephalins and intermittent blockade of the OGF–OGFr pathway in pathogenesis and treatment of these disorders.
Zinc deficiency causes neural tube defects through attenuation of p53 ubiquitylation
Authors: Li Huili , Zhang Jing , Niswander Lee 
Published: December 2018

ABSTRACT
Micronutrition is essential for neural tube closure, and zinc deficiency is associated with human neural tube defects. Here, we modeled zinc deficiency in mouse embryos, and used live imaging and molecular studies to determine how zinc deficiency affects neural tube closure. Embryos cultured with the zinc chelator TPEN failed to close the neural tube and showed excess apoptosis. TPEN-induced p53 protein stabilization in vivo and in neuroepithelial cell cultures and apoptosis was dependent on p53. Mechanistically, zinc deficiency resulted in disrupted interaction between p53 and the zinc-dependent E3 ubiquitin ligase Mdm2, and greatly reduced p53 ubiquitylation. Overexpression of human CHIP, a zinc-independent E3 ubiquitin ligase that targets p53, relieved TPEN-induced p53 stabilization and reduced apoptosis. Expression of p53 pro-apoptotic target genes was upregulated by zinc deficiency. Correspondingly, embryos cultured with p53 transcriptional activity inhibitor pifithrin-α could overcome TPEN-induced apoptosis and failure of neural tube closure. Our studies indicate that zinc deficiency disrupts neural tube closure through decreased p53 ubiquitylation, increased p53 stabilization and excess apoptosis.
O empreendedorismo de negócios entre enfermeiros
Authors: Chagas Sabrina Cássia , Milagres Priscila Néria , Silva Mariana Cristina Rodrigues , Cavalcante Ricardo Bezerra , Oliveira Patricia Peres de , Santos Regina Consolação dos 
Published: December 2018

Objetivo: caracterizar o empreendedorismo de negócios entre enfermeiros. Método: estudo de caso com abordagem quantitativa, apoiado nos conceitos de Schumpeter. Os dados foram coletados em um município mineiro, em 2015, por meio da aplicação de um questionário validado e entrevistas semiestruturadas com 10 enfermeiros empreendedores. O tratamento dos dados foi realizado por meio da análise de conteúdo, modalidade temático-categorial e os dados relacionados ao perfil e características comportamentais com auxílio do software STATA versão 12.0. Aprovado por Comitê de Ética em Pesquisa. Resultados: verificou-se que a maioria dos enfermeiros possuem empreendimentos registrados, de alta lucratividade e voltados para a assistência domiciliar. As características comportamentais: busca de informações, planejamento e monitoramento sistemático e persuasão e rede de contatos precisam ser potencializadas. Conclusão: o empreendedorismo de negócios entre os enfermeiros estudados conformou-se como uma oportunidade profissional vislumbrada a partir da necessidade de lucratividade e satisfação pessoal, o que os obrigou a deslocarem-se dos nichos tradicionais de trabalho.
Commutable whole blood reference materials for hemoglobin A1c validated on multiple clinical analyzers
Authors: Liu Hong , Wong Lingkai , Yong Sharon , Liu Qinde , Teo Tang Lin , Lee Tong Kooi , Loh Tze Ping , Sethi Sunil Kumar , Wong Moh Sim , Cosio Shelia Marie Delos Santos , Ho Clement K.M. , Setoh Johnson Weng Sung , Lim Sok Fong Maria , Lee Grace Lay Lay , Khalid Hafash , Lim Sharine , Lam Choong-Weng , Lee Mee-Yin , Yeo Chin Pin , Chincholkar Pallavi Ravikiran , Hawkins Robert , Ng Bih-Yann 
Published: December 2018

Abstract

Background
The measurement of hemoglobin A1c (HbA1c) is important for diagnosing diabetes mellitus as well as assessing glycemic control in diabetic patients. Commutable whole blood certified reference materials (CRMs) are needed in the measurement of HbA1c for method validation and/or as quality controls.

Methods
We developed three levels of hemolyzed whole blood CRMs for HbA1c. The certified values were determined using liquid chromatography-isotope dilution tandem mass spectrometry method (LC-IDMS/MS) where two “signature” hexapeptides of HbA1c and hemoglobin A0 (HbA0) were used as the calibration standards. The concentrations of the hexapeptide solutions were determined by amino acid analysis by the LC-IDMS/MS method using amino acid CRMs as the calibration standards. The commutability study was conducted by measuring 25 patient specimens and the whole blood CRMs by both LC-IDMS/MS method and various routine methods using six different clinical analyzers.

Results
The certified values were determined to be 35.1±2.0, 50.3±1.9 and 65.8±2.6 mmol/mol, respectively. These CRMs showed good commutability on five of the six clinical analyzers but showed poor commutability on one of the clinical analyzers that used similar method as two other analyzers where good commutability was observed.

Conclusions
With certified target values based on metrological traceability and good commutability on most of the clinical analyzers, the developed whole blood CRMs can be used for method validation or as quality control materials in the measurement of HbA1c. The commutability study results also underscored the need of commutability testing of clinical CRMs using various clinical analyzers.
Aktuelle nukleare Gefahren und die Probleme der Rüstungskontrolle
Authors: Thränert Oliver 
Published: December 2018

Kurzfassung
Atomare Gefahren wachsen als Folge der gegenwärtigen Großmächtekonkurrenz, wobei weder die USA, Russland noch China bereit sind, hinsichtlich der Kontrolle atomarer Rüstung politische Führungsverantwortung zu übernehmen. Auch die übrigen Kernwaffenmächte denken weniger an Rüstungskontrolle, sondern setzen auf die Modernisierung oder gar den Ausbau ihrer nuklearen Arsenale. Diese Bemühungen hängen immer mehr mit neuen Entwicklungen bei der Raketenabwehr oder Cyberfähigkeiten zusammen, was zusätzliche Unsicherheitsfaktoren schafft. Dieser Beitrag sucht zu erklären, warum nukleare Rüstungskontrolle nach Ende des Kalten Krieges nahezu zum Erliegen gekommen ist und argumentiert, dass dieses Konzept angesichts dieser globalen Entwicklungen wieder in den Vordergrund rücken sollte. Europa ist besonders gefordert, bezüglich strategischer Stabilität neue Denkanstöße zu erarbeiten und den Diskurs über die Neubelebung der nuklearen Rüstungskontrolle neu zu initiieren.
On eccentricity-based topological descriptors of water-soluble dendrimers
Authors: Iqbal Zahid , Ishaq Muhammad , Aslam Adnan , Gao Wei 
Published: December 2018

Abstract
Previous studies show that certain physical and chemical properties of chemical compounds are closely related with their molecular structure. As a theoretical basis, it provides a new way of thinking by analyzing the molecular structure of the compounds to understand their physical and chemical properties. The molecular topological indices are numerical invariants of a molecular graph and are useful to predict their bioactivity. Among these topological indices, the eccentric-connectivity index has a prominent place, because of its high degree of predictability of pharmaceutical properties. In this article, we compute the closed formulae of eccentric-connectivity–based indices and its corresponding polynomial for water-soluble perylenediimides-cored polyglycerol dendrimers. Furthermore, the edge version of eccentric-connectivity index for a new class of dendrimers is determined. The conclusions we obtained in this article illustrate the promising application prospects in the field of bioinformatics and nanomaterial engineering.
A Statistical Procedure for Genome-Wide Detection of QTL Hotspots Using Public Databases with Application to Rice
Authors: Yang Man-Hsia , Wu Dong-Hong , Kao Chen-Hung 
Published: December 2018

AbstractGenome-wide detection of quantitative trait loci (QTL) hotspots underlying variation in many molecular and phenotypic traits has been a key step in various biological studies since the QTL hotspots are highly informative and can be linked to the genes for the quantitative traits. Several statistical methods have been proposed to detect QTL hotspots. These hotspot detection methods rely heavily on permutation tests performed on summarized QTL data or individual-level data (with genotypes and phenotypes) from the genetical genomics experiments. In this article, we propose a statistical procedure for QTL hotspot detection by using the summarized QTL (interval) data collected in public web-accessible databases. First, a simple statistical method based on the uniform distribution is derived to convert the QTL interval data into the expected QTL frequency (EQF) matrix. And then, to account for the correlation structure among traits, the QTL for correlated traits are grouped together into the same categories to form a reduced EQF matrix. Furthermore, a permutation algorithm on the EQF elements or on the QTL intervals is developed to compute a sliding scale of EQF thresholds, ranging from strict to liberal, for assessing the significance of QTL hotspots. With grouping, much stricter thresholds can be obtained to avoid the detection of spurious hotspots. Real example analysis and simulation study are carried out to illustrate our procedure, evaluate the performances and compare with other methods. It shows that our procedure can control the genome-wide error rates at the target levels, provide appropriate thresholds for correlated data and is comparable to the methods using individual-level data in hotspot detection. Depending on the thresholds used, more than 100 hotspots are detected in GRAMENE rice database. We also perform a genome-wide comparative analysis of the detected hotspots and the known genes collected in the Rice Q-TARO database. The comparative analysis reveals that the hotspots and genes are conformable in the sense that they co-localize closely and are functionally related to relevant traits. Our statistical procedure can provide a framework for exploring the networks among QTL hotspots, genes and quantitative traits in biological studies. The R codes that produce both numerical and graphical outputs of QTL hotspot detection in the genome are available on the worldwide web http://www.stat.sinica.edu.tw/chkao/.
Randomized, Open-Label Phase II Study Comparing Capecitabine-Cisplatin Every 3 Weeks with S-1-Cisplatin Every 5 Weeks in Chemotherapy-Naïve Patients with HER2-Negative Advanced Gastric Cancer: OGSG1105, HERBIS-4A Trial
Authors: Kawakami Hisato , Takeno Atsushi , Endo Shunji , Makari Yoichi , Kawada Junji , Taniguchi Hirokazu , Tamura Shigeyuki , Sugimoto Naotoshi , Kimura Yutaka , Tamura Takao , Fujitani Kazumasa , Sakai Daisuke , Shimokawa Toshio , Kurokawa Yukinori , Satoh Taroh 
Published: December 2018

Abstract

Lessons Learned
Evidence has suggested that capecitabine-cisplatin is similar or possibly superior to S-1-cisplatin in terms of safety and efficacy for Japanese patients with advanced gastric cancer (AGC). As far as we are aware, our study is the first randomized trial of two regimens consisting of an oral fluoropyrimidine plus cisplatin in human epidermal growth receptor 2-negative AGC patients with measurable lesions.

Background
We performed a phase II study to evaluate the safety and efficacy of capecitabine plus cisplatin in comparison with S-1 plus cisplatin for first-line treatment of human epidermal growth receptor 2 (HER2)-negative advanced gastric cancer in Japan.

Methods
Eligible patients were randomly assigned to receive either capecitabine at 1,000 mg/m2 twice daily for 14 days plus cisplatin at 80 mg/m2 on day 1 every 3 weeks (n = 43) or S-1 at 40–60 mg twice daily for 21 days plus cisplatin at 60 mg/m2 on day 8 every 5 weeks (n = 41). The primary endpoint of the study was response rate.

Results
Response rate did not differ significantly between the capecitabine-cisplatin and S-1-cisplatin groups (53.5% vs. 51.2%, respectively, p &gt; .999). S-1-cisplatin tended to confer a better progression-free survival (PFS; median of 5.9 vs. 4.1 months, p = .284), overall survival (OS; median of 13.5 vs. 10.0 months, p = .290), and time to treatment failure (TTF; median of 4.5 vs. 3.1 months, p = .052) compared with capecitabine-cisplatin. Common hematologic toxicities of grade 3 or 4 included anemia and neutropenia in both groups. However, anorexia, fatigue, and hyponatremia of grade 3 or 4 occurred more frequently in the capecitabine-cisplatin group.

Conclusion
Capecitabine-cisplatin failed to demonstrate superior efficacy compared with S-1-cisplatin. The higher incidence of severe adverse events with capecitabine-cisplatin suggests that S-1-cisplatin should remain the standard first-line chemotherapy for HER2-negative advanced gastric cancer in Japan.