bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polymorphisms in cytokine genes influence cognitive and functional performance in a population aged 75 years and above
Authors: Fraga Vanessa G. , Guimarães Henrique C. , Teixeira Antônio L. , Barbosa Maira T. , Carvalho Maria G. , Caramelli Paulo , Gomes Karina B. 
Published: November 2016

ObjectiveTo investigate the frequency of the cytokine single nucleotide polymorphisms (SNPs) tumor necrosis factor (TNF)‐α−308G > A, tumor growth factor (TGF)‐β1 codon +10C > T, TGF‐β1 codon +25G > C, interleukin (IL)‐10 −1082A > G, IL‐10 −819C > T, IL‐10 −592C > A, IL‐6 −174G > C, and IFN‐γ+874T > A in a sample of healthy and cognitively impaired elderlies and to verify the probable association between these SNPs and cognitive and functional performance of subjects aged 75 years and above.Methods259 Brazilian subjects were included, comprising 81 with cognitive impairment no dementia (CIND) and 54 demented seniors (together made up the cognitively impaired group, CI) and 124 age‐matched and gender‐matched cognitively healthy controls (CHS). The genotyping was performed by multiplex polymerase chain reaction. The cognitive performance was evaluated by Mini‐Mental State Examination Brief Cognitive Screening Battery. The functional performance was accessed by Functional Activities Questionnaire.ResultsThe CClowergenotype of TGF‐β1 codon +25G > C was frequent in both patient groups. The TThighergenotype of INF‐γ+874T > A was less frequent in the dementia group. IL‐10 haplotypes of lower expression were more frequent among CIND and demented patients. In CI, individuals with genetic variants that produce higher expression of TGF‐β1, INF‐γ, and IL‐10 showed better normalized cognitive performance. Additionally, the Alowerallele of INF‐γ+874T > A was related to worse functional performance in CI, while the Alowerallele of TNF‐α−308G > A was associated with better cognitive and functional scores in the CIND group.ConclusionsOur findings suggest a potential role for certain cytokine SNPs in the development of CIND and dementia, which may influence the functional and cognitive performance of these patients. Copyright © 2016 John Wiley & Sons, Ltd.
Sex‐dependent independent prediction of incident diabetes by depressive symptoms
Authors: Akbaş‐Şimşek Tuğba , Onat Altan , Kaya Adnan , Tusun Eyyup , Yüksel Hüsniye , Can Günay 
Published: November 2016

ObjectiveTo study the predictive value of depressive symptoms (DeprSs) in a general population of Turkey for type 2 diabetes.MethodsResponses to three questions served to assess the sense of depression. Cox regression analyses were used regarding risk estimates for incident diabetes, after exclusion of prevalent cases of diabetes. Mean follow‐up consisted of 5.15 (±1.4) years.ResultsDepressive symptoms were present at baseline in 16.2% of the whole study sample, threefold in women than men. Reduced physical activity grade was the only significant covariate at baseline in men, while younger age and lower blood pressure were significantly different in women compared with those without DeprS. In men, presence of DeprS predicted incident diabetes at a significant 2.58‐fold relative risk (95% confidence interval 1.03; 6.44), after adjustment for age, systolic blood pressure, and antidepressant drug usage. When further covariates were added, waist circumference remained the only significant predictor, while DepS was attenuated to a relative risk of 2.12 (95% confidence interval 0.83; 5.40). DeprS was not associated with diabetes in women, whereas antidepressant drug usage only tended to be positively associated.ConclusionGender difference existed in the relationship between DeprS and incident diabetes. DeprS predicted subsequent development of diabetes in men alone, not in women. Copyright © 2016 John Wiley & Sons, Ltd.
Whole genome prediction and heritability of childhood asthma phenotypes
Authors: McGeachie Michael J. , Clemmer George L. , Croteau‐Chonka Damien C. , Castaldi Peter J. , Cho Michael H. , Sordillo Joanne E. , Lasky‐Su Jessica A. , Raby Benjamin A. , Tantisira Kelan G. , Weiss Scott T. 
Published: November 2016

AbstractIntroductionWhile whole genome prediction (WGP) methods have recently demonstrated successes in the prediction of complex genetic diseases, they have not yet been applied to asthma and related phenotypes. Longitudinal patterns of lung function differ between asthmatics, but these phenotypes have not been assessed for heritability or predictive ability. Herein, we assess the heritability and genetic predictability of asthma‐related phenotypes.MethodsWe applied several WGP methods to a well‐phenotyped cohort of 832 children with mild‐to‐moderate asthma from CAMP. We assessed narrow‐sense heritability and predictability for airway hyperresponsiveness, serum immunoglobulin E, blood eosinophil count, pre‐ and post‐bronchodilator forced expiratory volume in 1 sec (FEV1), bronchodilator response, steroid responsiveness, and longitudinal patterns of lung function (normal growth, reduced growth, early decline, and their combinations). Prediction accuracy was evaluated using a training/testing set split of the cohort.ResultsWe found that longitudinal lung function phenotypes demonstrated significant narrow‐sense heritability (reduced growth, 95%; normal growth with early decline, 55%). These same phenotypes also showed significant polygenic prediction (areas under the curve [AUCs] 56% to 62%). Including additional demographic covariates in the models increased prediction 4–8%, with reduced growth increasing from 62% to 66% AUC. We found that prediction with a genomic relatedness matrix was improved by filtering available SNPs based on chromatin evidence, and this result extended across cohorts.ConclusionsLongitudinal reduced lung function growth displayed extremely high heritability. All phenotypes with significant heritability showed significant polygenic prediction. Using SNP‐prioritization increased prediction across cohorts. WGP methods show promise in predicting asthma‐related heritable traits.
Role of resistance physical exercise in preventing testicular damage caused by chronic ethanol consumption in UChB rats
Authors: Dutra Gonçalves Gessica , Antunes Vieira Nichelle , Rodrigues Vieira Henrique , Dias Valério Aline , Elóisa Munhoz de Lion Siervo Gláucia , Fernanda Felipe Pinheiro Patricia , Eduardo Martinez Francisco , Alessandra Guarnier Flávia , Rampazzo Teixeira Giovana , Scantamburlo Alves Fernandes Glaura 
Published: November 2016

AbstractEthanol consumption is associated with spermatogenesis damage and testosterone level alterations. Alcohol remains the most commonly used substance among athletes and sports enthusiasts. This study evaluated whether resistance physical exercise can reduce the testicular damage caused by ethanol exposure. A total of 36 ethanol drinking (UChB) rats were divided into four groups: C (control rats), ETOH (ethanol consumption), ETOH + T (ethanol consumption + physical training), and T (group physical training). The physical training component of the T and ETOH + T groups was based on a resistance training model consisting of four sets of 10 jumps, with an increasing overload of 50–70% of the body weight attached to the chest three times per week. Rats in the ETOH and ETOH +T groups received 10% ethanol. At postnatal day 90, the rats were sacrificed. Blood sample was collected for hormonal analysis, and the testicles were weighed and processed for histopathological, morphometric, and immunohistochemical analyses. The ETOH group showed an increase in testosterone levels. The immunohistochemical of androgen receptor and the absolute weight of the testes were higher in the ETOH and ETOH + T groups, while the ETOH animals showed a decreased weight gain index. The number of abnormal seminiferous tubules increased in the ETOH and T groups compared to those in the control group (C); however, the association with treatment (ETOH + T group) prevented this effect and decreased caspase‐3 production. In conclusion, these findings show that the combination of ethanol consumption and resistance physical exercise can prevent testicular damage in adult UChB rats.
Staurosporine scaffold–based rational discovery of the wild‐type sparing reversible inhibitors of EGFR T790M gatekeeper mutant in lung cancer with analog‐sensitive kinase technology
Authors: Song Xiaoyun , Liu Xingcai , Ding Xi 
Published: November 2016

AbstractThe human epidermal growth factor receptor (EGFR) has been established as an attractive target for lung cancer therapy. However, an acquired EGFR T790M gatekeeper mutation is frequently observed in patients treated with first‐line anticancer agents such as gefitinib and erlotinib to cause drug resistance, largely limiting the application of small‐molecule kinase inhibitors in EGFR‐targeted chemotherapy. Previously, the reversible pan‐kinase inhibitor staurosporine and its several analogs such as Gö6976 and K252a have been reported to selectively inhibit the EGFR T790M mutant (EGFRT790M) over wild‐type kinase (EGFRWT), suggesting that the staurosporine scaffold is potentially to develop the wild‐type sparing reversible inhibitors of EGFRT790M. Here, we systematically evaluated the inhibitor response of 28 staurosporine scaffold–based compounds to EGFR T790M mutation at structural, energetic, and molecular levels by using an integrated in silico–in vitro analog‐sensitive (AS) kinase technology. With the strategy, we were able to identify 4 novel wild‐type sparing inhibitors UCN‐01, UCN‐02, AFN941, and SB‐218078 with high or moderate selectivity of 30‐, 45‐, 5‐, and 8‐fold for EGFRT790M over EGFRWT, respectively, which are comparable with or even better than that of the parent compound staurosporine (24‐fold). Molecular modeling and structural analysis revealed that van der Waals contacts and hydrophobic forces can form between the side chain of mutated residue Met790 and the pyrrolidinone moiety of inhibitor ligand UCN‐02, which may simultaneously improve the favorable interaction energy between the kinase and inhibitor, and reduce the unfavorable desolvation penalty upon the kinase‐inhibitor binding. A hydroxyl group of UCN‐02 additional to staurosporine locates at the pyrrolidinone moiety, which can largely alter the electronic distribution of pyrrolidinone moiety and thus promote the intermolecular interaction with Met790 residue. This can well explain the measured higher selectivity of UCN‐02 than staurosporine for mutant over wild‐type kinase.
The DNA aptamer binds stemness‐enriched cancer cells in pancreatic cancer
Authors: Kim Yoon‐Jin , Lee Hee Seung , Jung Dawoon E. , Kim Jeong Mi , Song Si Young 
Published: November 2016

AbstractPancreatic cancer remains one of the most common and lethal cancers. Most patients (80%) present with inoperable advanced pancreatic cancer at initial diagnosis, and their early diagnosis is a significant unmet challenge. Recent studies indicate that cancer, including pancreatic cancer, is initiated and propagated by cancer stem cells (CSCs). CSCs are responsible not only for the pathogenesis of cancer but also for the heterogeneity, malignant degree, anticancer therapy resistance, and recurrence of tumors. Therefore, the identification of CSCs may be a crucial stepping stone for overcoming this disastrous pancreatic cancer. Here, we investigated pancreatic CSC‐associated aptamers as a novel tool for diagnosis and therapeutic agents. Aptamers that bind to stemness‐enriched cancer cells in pancreatic cancer were developed by modified Cell‐SELEX method. Positive selection was performed by the sphere cells generated by pancreatic cancer cell line, HPAC, and then the aptamer pool was negatively selected by pancreatic normal cell line, HPDE. Aptamers 1 and 146 showing high specificity upon the KD values with 22.18 and 22.62 nM were selected. These 2 aptamers were validated by binding to HPAC sphere cells and to HPDE cells, and both aptamers showed specificity to HPAC sphere cells only. Aptamer‐positive cells showed high expression levels of CSC‐associated genes compared with the aptamer‐negative cells by FACS analysis. The colocalization of CD44, CD24, ESA, and CD133 was also observed in the aptamer‐positive cells by confocal microscopy. In the present study, these 2 pancreatic CSC‐associated aptamers may be potential candidates for novel diagnostic markers, CSC‐targeting drug delivery, or circulating tumor cell detection.
Fumarate Copolymer–Chitosan Cross‐Linked Scaffold Directed to Osteochondrogenic Tissue Engineering
Authors: Lastra María Laura , Molinuevo María Silvina , Cortizo Ana María , Cortizo María Susana 
Published: November 2016

Natural and synthetic cross‐linked polymers allow the improvement of cytocompatibility and mechanical properties of the individual polymers. In osteochondral lesions of big size it will be required the use of scaffolds to repair the lesion. In this work a borax cross‐linked scaffold based on fumarate‐vinyl acetate copolymer and chitosan directed to osteochondrondral tissue engineering is developed. The cross‐linked scaffolds and physical blends of the polymers are analyzed in based on their morphology, glass transition temperature, and mechanical properties. In addition, the stability, degradation behavior, and the swelling kinetics are studied. The results demonstrate that the borax cross‐linked scaffold exhibits hydrogel behavior with appropriated mechanical properties for bone and cartilage tissue regeneration. Bone marrow progenitor cells and primary chondrocytes are used to demonstrate its osteo‐ and chondrogenic properties, respectively, assessing the osteo‐ and chondroblastic growth and maturation, without evident signs of cytotoxicity as it is evaluated in an in vitro system.
image
Aliphatic Polyethers with Sulfate, Carboxylate, and Hydroxyl Side Groups—Do They Show Anticoagulant Properties?
Authors: Malineni Jagadeesh , Singh Smriti , Tillmann Sabine , Keul Helmut , Möller Martin 
Published: November 2016

There is increasing interest in the synthesis of low molecular weight heparin and heparan sulfate mimetic polymers because of their various potential biomedical applications. The functional activity of heparin and heparan sulfate is believed to arise from the presence of a number of functional groups, such as hydroxyl, carboxylate and sulfate groups. The design and synthesis of novel heparin‐mimetic polymers with a particular functionality poses a formidable challenge and requires carefully control of the selective conversion of functional groups on the polymer chain. Here, this study describes a simple and efficient synthetic protocol for the preparation of heparin‐mimetic linear polyglycidol copolymers based on the selective conversion of primary hydroxyl groups to carboxylic acids under ruthenium‐catalyzed selective dehydrogenation in basic aqueous solution. To achieve the anticoagulant activity of these polymers, primary hydroxyl groups are selectively converted to sulfate groups. The anticoagulant activity of the heparin mimics is studied by rotational thromboelastometry using EXTEM and INTEM assays. The environmentally benign process described herein provides an attractive route for the synthesis of heparin‐mimetic polymers with tailored functions such as anticoagulant activity.
image
Synthesis and Gas‐Transport Properties of Novel Copolymers Based on Tricyclononenes Containing One and Three Me3Si‐Groups
Authors: Chapala Pavel , Bermeshev Maxim , Starannikova Ludmila , Shantarovich Victor , Gavrilova Natalia , Lakhtin Valentin , Yampolskii Yuri , Finkelshtein Eugene 
Published: November 2016

In this work the authors report the preparation of new addition copolymers based on 3‐trimethylsilyltricyclononene‐7 (TCNSi1) and 3,3,4‐tris(trimethylsilyl)tricyclononene‐7 (TCNSi3). A number of high molecular weight copolymers are synthesized with the content of TCNSi3 units from 5 up to 20 mol% in the presence of catalyst Pd(OAc)2/[Ph3C]+[B(C6F5)4]− with the yields of 50%–80%. The obtained copolymers are amorphous. They possess large free volume elements (R
3/R
4) based on positron annihilating lifetime spectroscopy analysis and Brunauer–Emmett–Teller surface area up to 640 m2 g−1. Permeability coefficients of the obtained copolymers are determined for a wide range of gases He, H2, O2, N2, CO2, CH4, C2H6, C3H8, n‐C4H10. The correlation between the content of TCNSi3 units and gas permeation parameters of the resulting copolymers is explored. It is found that the introduction of TCNSi3 moieties results in the rise in gas permeability of the corresponding copolymers. Moreover, increase in TCNSi3 content in the copolymer leads to an increase of gas permeability.
image
Isocyanate‐ and Solvent‐Free Route to Thermoplastic Poly(amide‐urea) Derived from Renewable Resources
Authors: Ritter Benjamin S. , Mülhaupt Rolf 
Published: November 2016

This study reports on tailoring biobased aliphatic poly(amide‐urea) (PAU) thermoplastics by means of reactive extrusion requiring neither the use of diisocyanate monomers nor time‐consuming PAU polycondensation in a separate step prior to melt processing. Key intermediate is N,N′‐carbonyl‐biscaprolactam (CBC), which enables rapid and temperature‐programmable polycondensation of biobased diamines and difunctional aminoamides (AA) derived from diamines and dicarboxylic acids. Within a few minutes during melt processing using a twin‐screw extruder, CBC‐mediated advancement of biobased diaminoamides affords high molecular weight PAU. Whereas PAUs derived from short‐chain AAs are stiff and brittle materials with high melting temperatures close to thermal decomposition; the incorporation of AAs derived from sebacic acid and dimer fatty acid renders urea‐functional thermoplastics flexible and processable. Hence, the variation of oligomethylene segment lengths by incorporating short‐ and long‐chain AA building blocks in CBC‐mediated melt‐phase polycondensation governs PAU melting temperature (124–249 °C), Young's modulus (100–1900 MPa), tensile strength (6–51 MPa), and elongation at break (0.3–230%).
image
Reducing calories, fat, saturated fat, and sodium in restaurant menu items: Effects on consumer acceptance
Authors: Patel Anjali A. , Lopez Nanette V. , Lawless Harry T. , Njike Valentine , Beleche Mariana , Katz David L. 
Published: November 2016

ObjectiveTo assess consumer acceptance of reductions of calories, fat, saturated fat, and sodium to current restaurant recipes.MethodsTwenty‐four menu items, from six restaurant chains, were slightly modified and moderately modified by reducing targeted ingredients. Restaurant customers (n = 1,838) were recruited for a taste test and were blinded to the recipe version as well as the purpose of the study. Overall consumer acceptance was measured using a 9‐point hedonic (like/dislike) scale, likelihood to purchase scale, Just‐About‐Right (JAR) 5‐point scale, penalty analysis, and alienation analysis.ResultsOverall, modified recipes of 19 menu items were scored similar to (or better than) their respective current versions. Eleven menu items were found to be acceptable in the slightly modified recipe version, and eight menu items were found to be acceptable in the moderately modified recipe version. Acceptable ingredient modifications resulted in a reduction of up to 26% in calories and a reduction of up to 31% in sodium per serving.ConclusionsThe majority of restaurant menu items with small reductions of calories, fat, saturated fat, and sodium were acceptable. Given the frequency of eating foods away from home, these reductions could be effective in creating dietary improvements for restaurant diners.
Lipidomic profiling of high‐fat diet‐induced obesity in mice: Importance of cytochrome P450‐derived fatty acid epoxides
Authors: Wang Weicang , Yang Jun , Qi Weipeng , Yang Haixia , Wang Chang , Tan Bowen , Hammock Bruce D. , Park Yeonhwa , Kim Daeyoung , Zhang Guodong 
Published: November 2016

ObjectiveEnzymatic metabolism of polyunsaturated fatty acids leads to formation of bioactive lipid metabolites (LMs). Previous studies have shown that obesity leads to deregulation of LMs in adipose tissues. However, most previous studies have focused on a single or limited number of LMs, and few systematical analyses have been carried out.MethodsA LC‐MS/MS‐based lipidomics approach was used, which can analyze >100 LMs produced by cyclooxygenase, lipoxygenase, and cytochrome P450 (CYP) enzymes, to analyze the profile of LMs in high‐fat diet‐induced obesity in mice.ResultsLC‐MS/MS showed that high‐fat feeding significantly modulated profiles of LMs in adipose tissues. Among the three major polyunsaturated fatty acid metabolizing pathways (cyclooxygenase, lipoxygenase, and CYP), CYP‐derived fatty acid epoxides were the most dramatically altered LMs. Almost all types of fatty acid epoxides were reduced by 70% to 90% in adipose tissues of high‐fat diet‐fed mice. Consistent with the reduced levels of fatty acid epoxides, the gene expression of several CYP epoxygenases, including Cyp2j5, Cyp2j6, and Cyp2c44, was significantly reduced in adipose tissues of high‐fat diet‐fed mice.ConclusionsResults show that CYP‐derived fatty acid epoxides are the most responsive LMs in high‐fat diet‐induced obesity, suggesting that these LMs could play critical roles in obesity.
Vaccination and unexplained sudden death risk in Taiwanese infants
Authors: Huang Wan‐Ting , Chen Robert T. , Hsu Yu‐Chen , Glasser John W. , Rhodes Philip H. 
Published: November 2016

AbstractPurposeIn March 1992, eight infants who had died within 36 hours of receiving whole‐cell pertussis vaccine (diphtheria, tetanus, and whole‐cell pertussis [DTwP]) prompted the Taiwan health authorities to suspend its use. We conducted an investigation of vaccination and sudden unexplained infant death (SUID) and repeated it more recently after Taiwan switched to acellular pertussis vaccine (diphtheria, tetanus, and acellular pertussis [DTaP]) in 2010.MethodsAll SUIDs aged 31–364 days during 1990–1992 and 1996–2013 were selected from the death registration databases. The case–control investigation matched each case to two controls on clinic, sex, and birth date, whereas the follow‐up self‐controlled case series study compared risk of death during the 30‐day post‐vaccination risk periods with those in the control periods within the same case.ResultsSudden unexplained infant death was associated with never receiving DTwP (odds ratio 2.28, 95% confidence interval 1.25–4.15) in the case–control investigation. The odds ratios within 0–1, 2–7, 8–14, and 15–30 days of DTwP administration were 1.18, 0.26, 0.50, and 0.77. In the 1996–2013 self‐controlled case series studies, this temporal shift between DTwP and SUID was consistently observed for female (incidence rate ratio 1.70, 0.75, 1.01, and 0.84) but not male or DTaP recipients. A pooled analysis showed significant risk within 2 days of receiving DTwP in female infants (incidence rate ratio 1.66, 95% confidence interval 1.05–2.60).ConclusionsBeing unvaccinated and recent receipt of DTwP in female infants was significantly associated with SUID; the latter was consistent with a temporal shift pattern without overall increase in risk. The currently used pertussis vaccine, DTaP, did not increase risk of SUID. Copyright © 2016 John Wiley & Sons, Ltd.