bluuebunny/crossref_metadata_2025_split huggingface dataset:
Macrocyclic triamine derived glucose analogues for 99mTc(CO)3 labeling: synthesis and biological evaluation as potential tumor‐imaging agents
Authors: Liu Teli , Gan Qianqian , Zhang Junbo 
Published: February 2017

[99mTc(CO)3(H2O)3]+ has attracted great attention among 99mTc‐labeling techniques, due to its ease of preparation, readily substituted water molecules of the precursor fac‐[99mTc(CO)3(H2O)3]+ by a variety of functional groups, small size and inertness. Bifunctional chelator based on a macrocyclic polyamine framework shows easy complexation with [99mTc(CO)3(H2O)3]+ to produce stable complex. In this study, two novel 1, 5, 9‐triazacyclododecane derivatives containing a glucose group (6 and 7) were successfully synthesized by reacting different glucose‐azides with alkyne‐[12]aneN3 via the so‐called click chemistry and radiolabeled with [99mTc(CO)3(H2O)3]+ to form 99mTc(CO)3‐6 (C‐1‐substituted complex) and 99mTc(CO)3‐7 (C‐2‐substituted complex) in high yields. The complexes were stable in vitro over 6 h when incubated in saline at room temperature and in mouse serum at 37 °C. The partition coefficient results showed that they were hydrophilic. The biodistribution studies in Kunming mice bearing S 180 tumor showed both complexes showed accumulation in the tumor. Between them, 99mTc(CO)3‐7 had the advantages of much higher tumor uptake and tumor/muscle ratio. Compared with other reported 99mTc‐radiolabeled glucose derivatives, 99mTc(CO)3‐7 also showed a higher tumor uptake and tumor/muscle ratio, suggesting it would be a potential candidate for further development as a tumor‐imaging agent.
Are service‐delivery NGOs building state capacity in the Global South? Experiences from HIV/AIDS programmes in rural Uganda
Authors: Bukenya Badru 
Published: February 2017

AbstractService‐delivery NGOs are often attacked for abandoning the pursuit of ‘alternative development’ in favour of ‘technocratic’ forms of development. Yet some commentators argue that these organizations can have progressive impacts on political forms and processes. We investigate this debate through the lens of state building. Research into The AIDS Support Organisation's (TASO) work with the Ugandan government reveals that its state capacity building effects were both uneven and temporary. Although TASO played important roles in strengthening the bureaucratic ability of targeted hospitals to deliver HIV/AIDS services and increased the state's embeddedness in society in the targeted districts, it was less successful in expanding the infrastructural reach of the state in rural Uganda. We conclude that NGOs need longer time‐frames to achieve state building goals.
Association of chloride intracellular channel 4 and Indian hedgehog proteins with survival of patients with pancreatic ductal adenocarcinoma
Authors: Zou Qiong , Yang Zhulin , Li Daiqiang , Liu Ziru , yuan Yuan 
Published: February 2017

SummaryPancreatic cancer is the fourth most common cause of cancer‐related mortality. Novel molecular biomarkers need to be identified for personalized medicine and to improve survival. The aim of this study was to examine chloride intracellular channel 4 (CLIC4) and Indian Hedgehog (Ihh) expression in benign and malignant lesions of the pancreas and to examine the eventual association between CLIC4 and Ihh expression, with clinicopathological features and prognosis of pancreatic cancer. A retrospective study of specimens collected from January 2000 to December 2011 at the Department of Pathology of the Second and Third Xiangya Hospitals, Central South University was undertaken to explore this question. Immunohistochemistry of CLIC4 and Ihh was performed with EnVision™ in 106 pancreatic ductal adenocarcinoma specimens, 35 paracancer samples (2 cm away from the tumour, when possible or available), 55 benign lesions and 13 normal tissue samples. CLIC4 and Ihh expression in pancreatic ductal adenocarcinoma were significantly higher than in paracancer tissue and benign lesions (CLIC4: P = 0.009 and Ihh: P < 0.0001; CLIC4: P = 0.0004 and Ihh: P = 0.0001 respectively). CLIC4 and Ihh expression was negative in normal pancreatic tissues. The expression of CLIC4 and Ihh was associated significantly with tumour grade, lymph node metastasis, tumour invasion and poor overall survival. Thus CLIC4 and Ihh could serve as biological markers for the progression, metastasis and/or invasiveness of pancreatic ductal adenocarcinoma.
Predictors of influenza a molecular viral shedding in Hutterite communities
Authors: Wang Biao , Russell Margaret L. , Fonseca Kevin , Earn David J. D. , Horsman Gregory , Van Caeseele Paul , Chokani Khami , Vooght Mark , Babiuk Lorne , Walter Stephen D. , Loeb Mark 
Published: February 2017

BackgroundPatterns of influenza molecular viral shedding following influenza infection have been well established; predictors of viral shedding however remain uncertain.ObjectivesWe sought to determine factors associated with peak molecular viral load, duration of shedding, and viral area under the curve (AUC) in children and adult Hutterite colony members with laboratory‐confirmed influenza.MethodsA cohort study was conducted in Hutterite colonies in Alberta, Canada. Flocked nasal swabs were collected during three influenza seasons (2007‐2008 to 2009‐2010) from both symptomatic and asymptomatic individuals infected with influenza. Samples were tested by real‐time reverse‐transcription polymerase chain reaction for influenza A and influenza B, and the viral load was determined for influenza A‐positive samples.ResultsFor seasonal H1N1, younger age was associated with a larger AUC, female sex was associated with decreased peak viral load and reduced viral shedding duration, while the presence of comorbidity was associated with increased peak viral load. For H3N2, younger age was associated with increased peak viral load and increased AUC. For pandemic H1N1, younger age was associated with increased peak viral load and increased viral AUC, female sex was associated with reduced peak viral load, while inapparent infection was associated with reduced peak viral load, reduced viral shedding duration, and reduced viral AUC.ConclusionsPatterns of molecular viral shedding vary by age, sex, comorbidity, and the presence of symptoms. Predictor variables vary by influenza A subtype.
Validity of proxy‐reported height and weight to derive body mass index in adults participating in Special Olympics
Authors: Dobranowski Kristin , Lloyd Meghann , Côté Pierre , Balogh Robert 
Published: February 2017

BackgroundOverweight and obesity are common in adults with intellectual disabilities, which complicates their health. To meet their health needs, individuals with intellectual disability frequently rely on proxies to answer questions on their behalf. In the general population, the use of proxy‐reported height and weight to compute body mass index (BMI) has been validated, but not among adults with intellectual disability. The objective of this study was to determine the accuracy of proxy‐reported height, weight and derivedBMIamong adults with intellectual disability.MethodsProxies were asked to report height and weight on behalf of adults with intellectual disability who participate in Special Olympics Ontario; their answers were compared to measured height and weight.ResultsProxies reported height and weight accurately; the sensitivity of proxy reports for classifying individuals with intellectual disability as overweight and/or obese was 84.6%.ConclusionProxy reports may be useful when direct measurements of individuals with intellectual disability are not available.
Apples and Oranges: Four Definitions of Multiple Chronic Conditions and their Relationship to 30‐Day Hospital Readmission
Authors: Dattalo Melissa , DuGoff Eva , Ronk Katie , Kennelty Korey , Gilmore‐Bykovskyi Andrea , Kind Amy J. 
Published: February 2017

ObjectivesTo determine the extent of agreement between four commonly used definitions of multiple chronic conditions (MCCs) and compare each definition's ability to predict 30‐day hospital readmissions.DesignRetrospective cohort study.SettingNational Medicare claims data.ParticipantsRandom sample of Medicare beneficiaries discharged from the hospital from 2005 to 2009 (n = 710,609).MeasurementsBaseline chronic conditions were determined for each participant using four definitions of MCC. The primary outcome was all‐cause 30‐day hospital readmission. Agreement between MCC definitions was measured, and sensitivities and specificities for each definition's ability to identify patients experiencing a future readmission were calculated. Logistic regression was used to assess the ability of each MCC definition to predict 30‐day hospital readmission.ResultsThe sample prevalence of hospitalized Medicare beneficiaries with two or more chronic conditions ranged from 18.6% (Johns Hopkins Adjusted Clinical Groups (ACG) Case‐Mix System software) to 92.9% (Medicare Chronic Condition Warehouse (CCW)). There was slight to moderate agreement (kappa = 0.03–0.44) between pair‐wise combinations of MCC definitions. CCW‐defined MCC was the most sensitive (sensitivity 95.4%, specificity 7.4%), and ACG‐defined MCC was the most specific (sensitivity 32.7%, specificity 83.2%) predictor of being readmitted. In the fully adjusted model, the risk of readmission was higher for those with chronic condition Special Needs Plan (c‐SNP)‐defined MCCs (odds ratio (OR) = 1.50, 95% confidence interval (CI) = 1.47–1.52), Charlson Comorbidity Index–defined MCCs (OR = 1.45, 95% CI = 1.42–1.47), ACG‐defined MCCs (OR = 1.22, 95% CI = 1.19–1.25), and CCW‐defined MCCs (OR = 1.15, 95% CI = 1.11–1.19) than for those without MCCs.ConclusionMCC definitions demonstrate poor agreement and should not be used interchangeably. The two definitions with the greatest agreement (CCI, c‐SNP) were also the best predictors of 30‐day hospital readmissions.
What is the main mechanism of the origin of phosphorylation sites? Still an open question
Authors: Wang Yu‐Yu , Su Zhi‐Xi , Gu Xun 
Published: February 2017

AbstractIn spite of high‐throughput phosphoproteomics for protein kinase–phosphorylation site interactions, the evolutionary mechanism for the origin of protein phosphorylation remains a mystery. Pearlman and his colleagues proposed that some phosphorylation sites may have evolved from acidic amino acids, because those negatively charged amino acids (Asp/Glu) can mimic the phosphorylated state of a protein. Moreover, phosphorylation has the potential to conditionally restore the salt bridge that was originally constitutively formed by Asp/Glu. Although this insightful mimic hypothesis has been supported by several examples, we point out that the replacements from Asp/Glu to serine/threonine require at least two non‐synonymous nucleotide substitutions, casting some doubt about whether it is the major mechanism for the origin of phosphorylation. As the intermediate amino acid types, such as Ala/Asn/Gly, are not observed frequently, we have to invoke the hypothesis of double‐mutation driven by natural selection; that is, the very strong positive selection for the second mutation has overcome the deleterious effect caused by the first mutation. Furthermore, we propose an alternative evolutionary scenario that phosphorylation was primarily evolved to introduce negative charges to the protein surface, thus reducing spurious protein–protein interactions in vivo by electrostatic repulsion. The specific protein–protein interaction could be regulated when corresponding signals change surface charges by means of dephosphorylation and other recognition mechanisms. Probably this is a more universal mechanism that provided the first step toward the emergence of more accurate cell signaling and regulation. Further study is needed to distinguish between these hypotheses.
Hematological adverse effects and pharmacokinetics of ribavirin in pigs following intramuscular administration
Authors: Lee D.‐U. , Je S. H. , Yoo S. J. , Kwon T. , Shin J. Y. , Byun J. J. , Park J.‐H. , Jeong K.‐w. , Ku J.‐M. , Lyoo Y. S. 
Published: February 2017

Ribavirin (RBV) is a synthetic guanosine analog that is used as a drug against various viral diseases in humans. The in vitro antiviral effects of ribavirin against porcine viruses were demonstrated in several studies. The purposes of this study were to evaluate the adverse effects and pharmacokinetics of ribavirin following its intramuscular (IM) injection in pigs. Ribavirin was formulated as a double‐oil emulsion (RBV‐DOE) and gel (RBV‐Gel), which were injected into the pigs as single‐dose IM injections. After injection of RBV, all of the pigs were monitored. The collected serum and whole blood samples were analyzed by liquid chromatography–tandem mass spectrometry and complete blood count analysis, respectively. All of the ribavirin‐treated pigs showed significant decreases in body weight compared to the control groups. Severe clinical signs including dyspnea, anorexia, weakness, and depression were present in ribavirin‐treated pigs until 5 days postinjection (dpi). The ribavirin‐treated groups showed significant decrease in the number of red blood cells and hemoglobin concentration until 8 dpi. The mean half‐life of the RBV‐DOE and RBV‐Gel was 27.949 ± 2.783 h and 37.374 ± 3.502 h, respectively. The mean peak serum concentration (Cmax) and area under the serum concentration–time curve from time zero to infinity (AUCinf) of RBV‐DOE were 8340.000 ± 2562.577 ng/mL and 16 0095.430 ± 61 253.400 h·ng/mL, respectively. The Cmax and AUCinf of RBV‐Gel were 15 300.000 ± 3764.306 ng/mL and 207526.260 ± 63656.390 h·ng/mL, respectively. The results of this study provided the index of side effect and pharmacokinetics of ribavirin in pigs, which should be considered before clinical application.
Microaggressions, Discrimination, and Phenotype among African Americans: A Latent Class Analysis of the Impact of Skin Tone and BMI
Authors: Keith Verna M. , Nguyen Ann W. , Taylor Robert Joseph , Mouzon Dawne M. , Chatters Linda M. 
Published: February 2017

Data from the 2001–2003 National Survey of American Life are used to investigate the effects of phenotype on everyday experiences with discrimination among African Americans (N = 3343). Latent class analysis is used to identify four classes of discriminatory treatment: (1) low levels of discrimination, (2) disrespect and condescension, (3) character‐based discrimination, and (4) high levels of discrimination. We then employ latent class multinomial logistic regression to evaluate the association between skin tone and body weight and these four classes of discrimination. Designating the low‐level discrimination class as the reference group, findings revealed that respondents with darker skin were more likely to be classified into the disrespect/condescension and the high‐level microaggression types. BMI was unrelated to the discrimination type, although there was a significant interaction effect between gender and BMI. BMI was strongly and positively associated with membership in the disrespect and condescension type among men but not among women. These findings indicate that skin tone and body weight are two phenotypic characteristics that influence the type and frequency of discrimination experienced by African Americans.
Untangling the mechanisms underlying the links between religiousness, spirituality, and better health
Authors: Cheadle Alyssa C.D. , Dunkel Schetter Christine 
Published: February 2017

AbstractReligion and spirituality are major forces in the lives of Americans. A large and growing body of research indicates that specific aspects of religiousness and spirituality are associated with better physical and mental health. In this article, we differentiate some hypothesized mechanisms involving social, behavioral, psychological, and biological processes, and summarize some of the evidence pertaining to these pathways. This endeavor generates testable hypotheses for future research. Interdisciplinary research is especially well suited to examining these potential pathways, and social psychology can play a pivotal role in this future research agenda.
Molecular characterization of the C‐glucosylation for puerarin biosynthesis in Pueraria lobata
Authors: Wang Xin , Li Changfu , Zhou Chen , Li Jia , Zhang Yansheng 
Published: February 2017

SummaryC‐glycosyltransferases (CGTs) are important enzymes that are responsible for the synthesis of the C‐glycosides of flavonoids and isoflavonoids. Flavonoid CGTs have been molecularly characterized from several plant species; however, to date, no gene encoding an isoflavonoid CGT has been reported from any plant species. A significant example of an isoflavonoid C‐glycoside is puerarin, a compound that contributes to the major medicinal effects of Pueraria lobata. Little is known about the C‐glucosylation that occurs during puerarin biosynthesis. One possible route for puerarin synthesis is via the C‐glucosylation of daidzein. This study describes the molecular cloning and functional characterization of a novel glucosyltransferase (PlUGT43) from P. lobata. Biochemical analyses revealed that PlUGT43 possesses an activity for the C‐glucosylation of daidzein to puerarin; it shows activity with the isoflavones daidzein and genistein, but displays no activity towards other potential acceptors, including flavonoids. To validate the in vivo function of PlUGT43, the PlUGT43 gene was over‐expressed in soybean hairy roots that naturally synthesize daidzein but that do not produce puerarin. The expression of PlUGT43 led to the production of puerarin in the transgenic soybean hairy roots, confirming a role for PlUGT43 in puerarin biosynthesis.
Understanding Ethical Issues of Research Participation From the Perspective of Participating Children and Adolescents: A Systematic Review
Authors: Crane Stacey , Broome Marion E. 
Published: February 2017

ABSTRACTBackgroundThe past 20 years have seen distinct shifts in the way the participation of children and adolescents in research is viewed. This has been emphasized by the growing pediatric research enterprise. Additional information on children's and adolescents’ experiences during research participation is needed to better inform researchers on the ethical conduct of research with this vulnerable population.AimsThe objective of this analysis was to examine ethical issues in research with children and adolescents from their perspective as participants, including: assent, parental consent, risk perception, impact of research participation, and incentives.MethodsThis systematic review was conducted per the Long, Godfrey, Randall, Brettle, and Grant framework by means of an iterative searching process. Using the key words “research ethics” and “child or pediatric or adolescent,” PubMed, CINAHL, and EBSCOhost databases were searched to identify articles. Limitations placed on the searches were: English language, year of publication between 2003 and 2014, humans, abstract available, and age birth–18 years.FindingsTwenty‐three empiric studies were identified and formed the sample. Included studies represented a diverse range of areas of research, methods, settings, sample demographics, authors, and journals.Linking Evidence to ActionEven young children demonstrated the ability to understand essential elements of research, although there is variability in children's level of understanding. Trust was a significant contributing factor to children's and adolescents’ participation in research, and also shaped their assessments of risk. Research participation was mainly beneficial for children and adolescents. Incentives were mainly viewed positively, although concerns of possible undue influence were expressed.
TRIM25 Is Required for the Antiviral Activity of Zinc Finger Antiviral Protein
Authors: Zheng Xiaojiao , Wang Xinlu , Tu Fan , Wang Qin , Fan Zusen , Gao Guangxia 
Published: February 2017

ABSTRACT
Zinc finger antiviral protein (ZAP) is a host factor that specifically inhibits the replication of certain viruses by binding to viral mRNAs and repressing the translation and/or promoting the degradation of target mRNA. In addition, ZAP regulates the expression of certain cellular genes. Here, we report that tripartite motif-containing protein 25 (TRIM25), a ubiquitin E3 ligase, is required for the antiviral activity of ZAP. Downregulation of endogenous TRIM25 abolished ZAP's antiviral activity. The E3 ligase activity of TRIM25 is required for this regulation. TRIM25 mediated ZAP ubiquitination, but the ubiquitination of ZAP itself did not seem to be required for its antiviral activity. Downregulation of endogenous ubiquitin or overexpression of the deubiquitinase OTUB1 impaired ZAP's activity. We provide evidence indicating that TRIM25 modulates the target RNA binding activity of ZAP. These results uncover a mechanism by which the antiviral activity of ZAP is regulated.

IMPORTANCE
ZAP is a host antiviral factor that specifically inhibits the replication of certain viruses, including HIV-1, Sindbis virus, and Ebola virus. ZAP binds directly to target mRNA, and it represses the translation and promotes the degradation of target mRNA. While the mechanisms by which ZAP posttranscriptionally inhibits target RNA expression have been extensively studied, how its antiviral activity is regulated is not very clear. Here, we report that TRIM25, a ubiquitin E3 ligase, is required for the antiviral activity of ZAP. Downregulation of endogenous TRIM25 remarkably abolished ZAP's activity. TRIM25 is required for ZAP optimal binding to target mRNA. These results help us to better understand how the antiviral activity of ZAP is regulated.
Dietary phytochemical intake from foods and health outcomes: a systematic review protocol and preliminary scoping
Authors: Probst Yasmine C , Guan Vivienne X , Kent Katherine 
Published: February 2017

IntroductionDietary phytochemicals are found in plant-based foods such as fruits, vegetables and grains and may be categorised in a nested hierarchical manner with many hundred individual phytochemicals identified to date. To associate phytochemical intakes with positive health outcomes, a fundamental step is to accurately estimate the dietary phytochemical intake from foods reported. The purpose of this systematic review protocol is to describe the process to be undertaken to summarise the evidence for food-based dietary phytochemical intakes and health outcomes for adults.Methods and analysisThe review will be undertaken following the PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions using the Review Manager software. Phytochemical subclasses (phenolic acids, flavanols, etc) will be used to search for relevant studies using the Web of Science and Scopus scientific databases. The retrieved studies will be screened based on inclusion of natural whole food items and health outcomes. Phytochemical studies related to cardiovascular disease, cancer, overweight, glucose tolerance, digestive, reproductive, macular and bone health and mental disorders, fatigue and immunity will be examined based on prior scoping. The evidence will be aggregated by the food types and health outcomes. Comparison of differences in the outcomes for randomised controlled trials and observational studies will be undertaken. The strength of the review lies in its focus on whole food items and health conditions rather than one type of phytochemical related to one single health condition. Subgroup and sensitivity analyses will be conducted where an adequate number of publications are found per phytochemical subclass.DisseminationBy comparing the outcomes from experimental and observational studies, the review will determine whether the overall conclusions related to the phytochemical subclasses are the same between study types for the identified health conditions. This is useful to public health policymakers and health professionals alike.Trial registration number#CRD42014015610.