bluuebunny/crossref_metadata_2025_split huggingface dataset:
Varenicline in smokers with diabetes: A pooled analysis of 15 randomized, placebo‐controlled studies of varenicline
Authors: Tonstad Serena , Lawrence David 
Published: May 2016

AbstractAims/IntroductionStopping smoking deserves high priority in preventing complications of diabetes; however, only sparse data are available regarding the efficacy of pharmacotherapy in smokers with diabetes. We assessed the efficacy and safety of varenicline in smokers with diabetes who participated in 15 double‐blind, randomized, placebo‐controlled studies.Materials and MethodsThis retrospective pooled analysis included data from smokers of ≥10 cigarettes per day with diabetes. Participants received varenicline 1 mg b.i.d. or placebo for 12 weeks. We examined carbon monoxide‐confirmed continuous abstinence rates (CARs) for weeks 9–12, 9–24 and 9–52, and compared safety in participants with and without diabetes.ResultsOf 6,771 participants, 323 had diabetes (varenicline n = 162; placebo n = 161). Week 9–12 CAR was higher with varenicline than placebo (43.8% vs 24.8%; odds ratio 2.36, 95% CI 1.47–3.79), as was week 9–24 CAR (27.5% vs 14.4%; odds ratio 2.25, 95% CI 1.27–4.00). Week 9–52 CAR was 18.4% for varenicline and 10.1% for placebo (odds ratio 2.00, 95% CI 0.90–4.49). The most commonly‐reported adverse events in participants with diabetes for varenicline vs placebo were: nausea (27.2% vs 8.1%); headache (9.3% vs 9.9%); and insomnia (8.6% vs 5.6%), incidences that were similar in participants without diabetes (29.6% vs 9.7%; 13.4% vs 10.9%; and 11.4% vs 7.1%, respectively). Weight gain in quitters with diabetes (1.7 kg) was similar to that of those without diabetes (2.1 kg).ConclusionsVarenicline was an effective and well‐tolerated aid for smoking cessation in individuals with diabetes. Safety was comparable with participants without diabetes.
Effect of Vacuum Drying Temperature on Drying Kinetics, Effective Moisture Diffusivity and Quality of Peeled Litchi (Litchi chinensis Sonn.)
Authors: Richter Reis Felipe , Ivahashi Marcela Massumi , Guéniat Rosa Aluísio Henrique 
Published: May 2016

AbstractThis study aimed at investigating the effect of vacuum drying temperature on drying kinetics, drying rates, effective moisture diffusivity and quality parameters of litchi fruits. Peeled litchi quarters were dried at 50–70 °C at an absolute pressure of 8 kPa. Results show that the vacuum drying occurred in the falling rate period. Drying rates increased with drying temperature. The Page model provided the best fit to the drying kinetics. Effective moisture diffusivity ranged between 1.997 × 10−9 and 5.012 × 10−9 m2/s. The temperature dependence of the effective moisture diffusivity was well described by an Arrhenius‐type equation. The activation energy for moisture diffusion was 41.81 kJ/mol. Drying temperature did not significantly affect product sensory acceptance, density, shrinkage and rehydration. The products dried at 50 and 70 °C presented slightly superior texture and flavor, while the product dried at 60 °C presented significantly higher lightness and lower water activity.Practical ApplicationsThis work provides valuable information on the vacuum drying of litchi fruits, which are appreciated in many countries due to their pleasant sensory characteristics. Vacuum drying is not a costly drying method. At the same time, vacuum drying produces dried foods of relatively good quality. This study could be used as a reference by small and medium scale food processors interested in producing dried litchi of good quality with relatively low investment in equipment. The understanding of the influence of drying temperature on quality parameters is useful for deciding which temperature is more appropriate depending on the desired quality aspects, while the calculation of engineering parameters is important for designing the drying process.
Role of implant configurations supporting three‐unit fixed partial denture on mandibular bone response: biological‐data‐based finite element study
Authors: Yoda N. , Liao Z. , Chen J. , Sasaki K. , Swain M. , Li Q. 
Published: May 2016

SummaryImplant‐supported fixed partial denture with cantilever extension can transfer the excessive load to the bone around implants and stress/strain concentration potentially leading to bone resorption. This study investigated the effects of implant configurations supporting three‐unit fixed partial denture (FPD) on the stress and strain distribution in the peri‐implant bone by combining clinically measured time‐dependent loading data and finite element (FE) analysis. A 3‐dimensional mandibular model was constructed based on computed tomography (CT) images. Four different configurations of implants supporting 3‐unit FPDs, namely three implant‐supported FPD, conventional three‐unit bridge FPD, distal cantilever FPD and mesial cantilever FPD, were modelled. The FPDs were virtually inserted to the molar area in the mandibular FE models. The FPDs were loaded according to time‐dependent in vivo‐measured 3‐dimensional loading data during chewing. The von Mises stress (VMS) and equivalent strain (EQS) in peri‐implant bone regions were evaluated as mechanical stimuli. During the chewing cycles, the regions near implant necks and bottom apexes experienced high VMS and EQS than the middle regions in all implant‐supported FPD configurations. Higher VMS and EQS values were also observed at the implant neck region adjacent to the cantilever extension in the cantilevered configurations. The patient‐specific dynamic loading data and CT‐based reconstruction of full 3D mandibular allowed us to model the biomechanical responses more realistically. The results provided data for clinical assessment of implant configuration to improve longevity and reliability of the implant‐supported FPD restoration.
Evolutionary melting pots: a biodiversity hotspot shaped by ring diversifications around the Black Sea in the Eastern tree frog (Hyla orientalis)
Authors: Dufresnes Christophe , Litvinchuk Spartak N. , Leuenberger Julien , Ghali Karim , Zinenko Oleksandr , Stöck Matthias , Perrin Nicolas 
Published: May 2016

AbstractHotspots of intraspecific genetic diversity, which are of primary importance for the conservation of species, have been associated with glacial refugia, that is areas where species survived the Quaternary climatic oscillations. However, the proximate mechanisms generating these hotspots remain an open issue. Hotspots may reflect the long‐term persistence of large refugial populations; alternatively, they may result from allopatric differentiation between small and isolated populations, that later admixed. Here, we test these two scenarios in a widely distributed species of tree frog, Hyla orientalis, which inhabits Asia Minor and southeastern Europe. We apply a fine‐scale phylogeographic survey, combining fast‐evolving mitochondrial and nuclear markers, with a dense sampling throughout the range, as well as ecological niche modelling, to understand what shaped the genetic variation of this species. We documented an important diversity centre around the Black Sea, composed of multiple allopatric and/or parapatric diversifications, likely driven by a combination of Pleistocene climatic fluctuations and complex regional topography. Remarkably, this diversification forms a ring around the Black Sea, from the Caucasus through Anatolia and eastern Europe, with terminal forms coming into contact and partially admixing in Crimea. Our results support the view that glacial refugia generate rather than host genetic diversity and can also function as evolutionary melting pots of biodiversity. Moreover, we report a new case of ring diversification, triggered by a large, yet cohesive dispersal barrier, a very rare situation in nature. Finally, we emphasize the Black Sea region as an important centre of intraspecific diversity in the Palearctic with implications for conservation.
Limitations of PCR‐based molecular markers to identify male‐sterile and maintainer plants from Indian onion (Allium cepa L.) populations
Authors: Khar Anil , Saini Navinder 
Published: May 2016

AbstractThe main aim of this study was to validate PCR markers for determining cytoplasm and genotypes at the Ms locus in short‐day onion. Three cytoplasmic (OSN, MKFR and accD) and four nuclear (OPT, jnurf13, AcSKP1 and AcPMS1) markers were employed. Sel. 121‐1 had 100% S cytoplasm, whereas Sel. 121‐2, ‘Pusa Red’ and ‘Pusa Madhavi’ had 88%, 33% and 17% S cytoplasm, respectively. ‘Early Grano’ and ‘Pusa Riddhi’ did not possess S cytoplasm. Observations in 33 commercial varieties revealed two with sterile (S) cytoplasm. Nuclear markers were not found in linkage disequilibrium with the Ms locus, and the constitution of Ms alleles by OPT was different from other three markers, which were in conformity with each other. The other three markers predicted that most of the plants should be homozygous recessive. Anther colour also did not confirm the sterility status. It can be concluded that accD may be used for cytoplasm determination based on the ease of its use. For the Ms locus tagging, more markers are needed to be evaluated to isolate maintainer lines from open‐pollinated populations.
Role of deposit‐feeding sea cucumbers in integrated multitrophic aquaculture: progress, problems, potential and future challenges
Authors: Zamora Leonardo Nicolas , Yuan Xiutang , Carton Alexander Guy , Slater Matthew James 
Published: May 2016

AbstractThere is significant commercial and research interest in the application of sea cucumbers as nutrient recyclers and processors of particulate waste in polyculture or integrated multitrophic aquaculture (IMTA) systems. The following article reviews examples of existing IMTA systems operating with sea cucumbers, and details the role and effect of several sea cucumber species in experimental and pilot IMTA systems worldwide. Historical observations and quantification of impacts of sea cucumber deposit‐feeding and locomotion are examined, as is the development and testing of concepts for the application of sea cucumbers in sediment remediation and site recovery. The extension of applied IMTA systems is reported, from basic piloting through to economically viable farming systems operating at commercial scales. The near‐global recognition of the ecological and economic value of deposit‐feeding sea cucumbers in IMTA applications within existing and developing aquaculture industries is discussed. Predictions and recommendations are offered for optimal development of sea cucumber IMTA globally. Future directions within the industry are indicated, and key areas of ecological, biological and commercial concern are highlighted to be kept in mind and addressed in a precautionary manner as the industry develops.
Reduced transforming growth factor β1 (TGF‐β1) in the repair of airway epithelial cells of children with asthma
Authors: Ling Kak‐Ming , Sutanto Erika N. , Iosifidis Thomas , Kicic‐Starcevich Elizabeth , Looi Kevin , Garratt Luke W. , Martinovich Kelly M. , Lannigan Francis J. , Knight Darryl A. , Stick Stephen M. , Kicic Anthony 
Published: May 2016

AbstractBackground and objectiveEvidence into the role of TGF‐β1 in airway epithelial repair in asthma is still controversial. This study tested the hypothesis that the reduced TGF‐β1 levels previously observed in paediatric asthmatic airway epithelial cells directly contribute to the dysregulated repair seen in these cells.MethodsPrimary airway epithelial cells (pAEC) from children with asthma (n = 16) and non‐asthmatic subjects (n = 20) were isolated, and subcultured for investigation of TGF‐β1 gene and protein via quantitative polymerase chain reaction (qPCR) and enzyme‐linked immunosorbent assay (ELISA), respectively. Expression of other associated genes such as integrins αvβ6, αvβ8 and MT1‐MMP were also tested. Small interfering RNA (siRNA) was employed to assess the role of TGF‐β1 during wound repair.ResultsTGF‐β1 gene and protein expression were significantly downregulated in asthmatic pAEC over the course of repair, compared with cells from non‐asthmatic children. Messenger RNA (mRNA) expression of TGF‐β1 was also directly implicated in non‐asthmatic and asthmatic pAEC proliferation over their quiescent counterparts. Small interfering RNA‐mediated knockdown of TGF‐β1 compromised repair in non‐asthmatic pAEC and exacerbated the dysregulated repair seen in asthmatic pAEC. Expression of major TGF‐β1 activators of epithelial cells, integrin αvβ6 and αvβ8 was also measured and there was no difference in αvβ6 gene expression between the two cohorts. Although integrin αvβ8 gene expression was significantly higher in asthmatic pAEC, the expression of MT1‐MMP (MMP14) which facilitates the αvβ8 mediated TGF‐β1 activation was significantly downregulated.ConclusionOur data has highlighted the importance of TGF‐β1 in pAEC wound repair in vitro. The significantly lower levels seen in asthmatic pAEC subsequently contributes to the dysregulated repair observed in these cells.
Predictors of early breastfeeding cessation among HIV‐infected women in Botswana
Authors: Ogwu Anthony , Moyo Sikhulile , Powis Kathleen , Asmelash Aida , Lockman Shahin , Moffat Claire , Leidner Jean , Makhema Joseph , Essex Max , Shapiro Roger 
Published: May 2016

AbstractObjectiveInfants born to HIV‐infected women receiving antiretroviral treatment (ART) can be breastfed through at least 6 months with very low risk of HIV acquisition. We aimed to identify demographic and cultural factors that may influence mothers' willingness to breastfeed for the recommended duration.MethodsWe evaluated factors associated with early cessation of breastfeeding (i.e. before 5 months post‐partum) in a randomized clinical trial evaluating different ART regimens used for prevention of mother‐to‐child transmission during breastfeeding in Botswana. Univariate and multivariable Cox regressions were used to describe predictors of early exclusive BF cessation.ResultsAmong 677 women who started breastfeeding, the median time to breastfeeding cessation was 178 days (IQR 150–181) and 25.1% weaned early. In multivariable analysis, urban location (aHR = 1.86 95%CI 1.27–2.73; P = 0.002), salaried employment or being a student (aHR = 2.78 95% CI 1.63–4.75; P < 0.001) and infant hospitalisation before weaning (aHR = 2.04 95% CI 1.21–3.45; P = 0.008) were independently and significantly associated with early BF cessation.ConclusionsImproved support for breastfeeding among employed mothers, especially in urban settings, may allow HIV‐infected women who are receiving ART prophylaxis to breastfeed longer.
Built Environment and Active Transport to School (BEATS) Study: protocol for a cross-sectional study
Authors: Mandic Sandra , Williams John , Moore Antoni , Hopkins Debbie , Flaherty Charlotte , Wilson Gordon , García Bengoechea Enrique , Spence John C 
Published: May 2016

IntroductionActive transport to school (ATS) is a convenient way to increase physical activity and undertake an environmentally sustainable travel practice. The Built Environment and Active Transport to School (BEATS) Study examines ATS in adolescents in Dunedin, New Zealand, using ecological models for active transport that account for individual, social, environmental and policy factors. The study objectives are to: (1) understand the reasons behind adolescents and their parents' choice of transport mode to school; (2) examine the interaction between the transport choices, built environment, physical activity and weight status in adolescents; and (3) identify policies that promote or hinder ATS in adolescents.Methods and analysisThe study will use a mixed-method approach incorporating both quantitative (surveys, anthropometry, accelerometers, Geographic Information System (GIS) analysis, mapping) and qualitative methods (focus groups, interviews) to gather data from students, parents, teachers and school principals. The core data will include accelerometer-measured physical activity, anthropometry, GIS measures of the built environment and the use of maps indicating route to school (students)/work (parents) and perceived safe/unsafe areas along the route. To provide comprehensive data for understanding how to change the infrastructure to support ATS, the study will also examine complementary variables such as individual, family and social factors, including student and parental perceptions of walking and cycling to school, parental perceptions of different modes of transport to school, perceptions of the neighbourhood environment, route to school (students)/work (parents), perceptions of driving, use of information communication technology, reasons for choosing a particular school and student and parental physical activity habits, screen time and weight status. The study has achieved a 100% school recruitment rate (12 secondary schools).Ethics and disseminationThe study has been approved by the University of Otago Ethics Committee. The results will be actively disseminated through reports and presentations to stakeholders, symposiums and scientific publications.
Adenosine 2B Receptor Expression on Cancer Cells Promotes Metastasis
Authors: Mittal Deepak , Sinha Debottam , Barkauskas Deborah , Young Arabella , Kalimutho Murugan , Stannard Kimberley , Caramia Franco , Haibe-Kains Benjamin , Stagg John , Khanna Kum Kum , Loi Sherene , Smyth Mark J. 
Published: May 2016

Abstract
Adenosine plays an important role in inflammation and tumor development, progression, and responses to therapy. We show that an adenosine 2B receptor inhibitor (A2BRi) decreases both experimental and spontaneous metastasis and combines with chemotherapy or immune checkpoint inhibitors in mouse models of melanoma and triple-negative breast cancer (TNBC) metastasis. Decreased metastasis upon A2BR inhibition is independent of host A2BR and lymphocytes and myeloid cells. Knockdown of A2BR on mouse and human cancer cells reduces their metastasis in vivo and decreases their viability and colony-forming ability, while transiently delaying cell-cycle arrest in vitro. The prometastatic activity of adenosine is partly tumor A2BR dependent and independent of host A2BR expression. In humans, TNBC cell lines express higher A2BR than luminal and Her2+ breast cancer cell lines, and high expression of A2BR is associated with worse prognosis in TNBC. Collectively, high A2BR on mouse and human tumors promotes cancer metastasis and is an ideal candidate for therapeutic intervention. Cancer Res; 76(15); 4372–82. ©2016 AACR.
Tyrosine Kinase Signaling in Clear Cell and Papillary Renal Cell Carcinoma Revealed by Mass Spectrometry–Based Phosphotyrosine Proteomics
Authors: Haake Scott M. , Li Jiannong , Bai Yun , Kinose Fumi , Fang Bin , Welsh Eric A. , Zent Roy , Dhillon Jasreman , Pow-Sang Julio M. , Chen Y. Ann , Koomen John M. , Rathmell W. Kimryn , Fishman Mayer , Haura Eric B. 
Published: May 2016

Abstract
Purpose: Targeted therapies in renal cell carcinoma (RCC) are limited by acquired resistance. Novel therapeutic targets are needed to combat resistance and, ideally, target the unique biology of RCC subtypes.
Experimental Design: Tyrosine kinases provide critical oncogenic signaling and their inhibition has significantly impacted cancer care. To describe a landscape of tyrosine kinase activity in RCC that could inform novel therapeutic strategies, we performed a mass spectrometry–based system-wide survey of tyrosine phosphorylation in 10 RCC cell lines as well as 15 clear cell and 15 papillary RCC human tumors. To prioritize identified tyrosine kinases for further analysis, a 63 tyrosine kinase inhibitor (TKI) drug screen was performed.
Results: Among the cell lines, 28 unique tyrosine phosphosites were identified across 19 kinases and phosphatases including EGFR, MET, JAK2, and FAK in nearly all samples. Multiple FAK TKIs decreased cell viability by at least 50% and inhibited RCC cell line adhesion, invasion, and proliferation. Among the tumors, 49 unique tyrosine phosphosites were identified across 44 kinases and phosphatases. FAK pY576/7 was found in all tumors and many cell lines, whereas DDR1 pY792/6 was preferentially enriched in the papillary RCC tumors. Both tyrosine kinases are capable of transmitting signals from the extracellular matrix and emerged as novel RCC therapeutic targets.
Conclusions: Tyrosine kinase profiling informs novel therapeutic strategies in RCC and highlights the unique biology among kidney cancer subtypes. Clin Cancer Res; 22(22); 5605–16. ©2016 AACR.
Repurposing Sunitinib with Oncolytic Reovirus as a Novel Immunotherapeutic Strategy for Renal Cell Carcinoma
Authors: Lawson Keith A. , Mostafa Ahmed A. , Shi Zhong Qiao , Spurrell Jason , Chen Wenqian , Kawakami Jun , Gratton Kathy , Thakur Satbir , Morris Donald G. 
Published: May 2016

Abstract
Purpose: In addition to their direct cytopathic effects, oncolytic viruses are capable of priming antitumor immune responses. However, strategies to enhance the immunotherapeutic potential of these agents are lacking. Here, we investigated the ability of the multi-tyrosine kinase inhibitor and first-line metastatic renal cell carcinoma (RCC) agent, sunitinib, to augment the antitumor immune response generated by oncolytic reovirus.
Experimental Design: In vitro, oncolysis and chemokine production were assessed in a panel of human and murine RCC cell lines after exposure to reovirus, sunitinib, or their combination. In vivo, the RENCA syngeneic murine model of RCC was employed to determine therapeutic and tumor-specific immune responses after treatment with reovirus (intratumoral), sunitinib, or their combination. Parallel investigations employing the KLN205 syngeneic murine model of lung squamous cell carcinoma (NSCLC) were conducted for further validation.
Results: Reovirus-mediated oncolysis and chemokine production was observed following RCC infection. Reovirus monotherapy reduced tumor burden and was capable of generating a systemic adaptive antitumor immune response evidenced by increased numbers of tumor-specific CD8+ IFNγ-producing cells. Coadministration of sunitinib with reovirus further reduced tumor burden resulting in improved survival, decreased accumulation of immune suppressor cells, and the establishment of protective immunity upon tumor rechallenge. Similar results were observed for KLN205 tumor–bearing mice, highlighting the potential broad applicability of this approach.
Conclusions: The ability to repurpose sunitinib for augmentation of reovirus' immunotherapeutic efficacy positions this novel combination therapy as an attractive strategy ready for clinical testing against a range of histologies, including RCC and NSCLC. Clin Cancer Res; 22(23); 5839–50. ©2016 AACR.
ГІГІЄНІЧНА ОЦІНКА НАСЛІДКІВ ХЛОРУВАННЯ ВОДИ ПОВЕРХНЕВИХ ВОДОЙМ УКРАЇНСЬКОГО ПРИДУНАВ’Я
Authors: Kovalchuk L. J. , Mokіenko A. V. , Petrenko N. F. 
Published: May 2016

У роботі представлено результати гігієнічної оцінки наслідків хлорування води поверхневих водойм Українського Придунав’я. Встановлено, що хлорування води озер Кагул, Ялпуг, Катлабух супроводжується достовірним (р&lt;0,05) ростом утворення високих рівнів хлороформу залежно від дози введеного хлору, які в 2 (при хлоруванні води озера Кагул дозою хлору 1 мг/дм<sup>3</sup>) – 20 разів (при хлоруванні води озера Катлабух дозою хлору 7 мг/дм<sup>3</sup>) перевищують чинний норматив цієї сполуки для питної води. Це створює додатковий ризик канцерогенної захворюванності населення. Висловлено думку, що хлороформ та інші тригалометани (ТГМ) є тільки складовою токсичного та віддалених впливів на стан здоров’я споживачів хлорованої води поверхневих водойм. Обґрунтовано необхідність досліджень хлорвмісних сполук та продуктів трансформації забруднювачів у процесі хлорування та доцільність дослідження і впровадження альтернативних хлоруванню засобів знезараження води, наприклад діоксиду хлору.