bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanism of lipid‐lowering action of the dipeptidyl peptidase‐4 inhibitor, anagliptin, in low‐density lipoprotein receptor‐deficient mice
Authors: Yano Wataru , Inoue Noriyuki , Ito Shiori , Itou Takahiro , Yasumura Misako , Yoshinaka Yasunobu , Hagita Sumihiko , Goto Moritaka , Nakagawa Takashi , Inoue Keisuke , Tanabe Sohei , Kaku Kohei 
Published: November 2016

AbstractAims/IntroductionDipeptidyl peptidase‐4 inhibitors are used for treatment of patients with type 2 diabetes. In addition to glycemic control, these agents showed beneficial effects on lipid metabolism in clinical trials. However, the mechanism underlying the lipid‐lowering effect of dipeptidyl peptidase‐4 inhibitors remains unclear. Here, we investigated the lipid‐lowering efficacy of anagliptin in a hyperlipidemic animal model, and examined the mechanism of action.Materials and MethodsMale low‐density lipoprotein receptor‐deficient mice were administered 0.3% anagliptin in their diet. Plasma lipid levels were assayed and lipoprotein profile was analyzed using high‐performance liquid chromatography. Hepatic gene expression was examined by deoxyribonucleic acid microarray and quantitative polymerase chain reaction analyses. Sterol regulatory element‐binding protein transactivation assay was carried out in vitro.ResultsAnagliptin treatment significantly decreased the plasma total cholesterol (14% reduction, P < 0.01) and triglyceride levels (27% reduction, P < 0.01). Both low‐density lipoprotein cholesterol and very low‐density lipoprotein cholesterol were also decreased significantly by anagliptin treatment. Sterol regulatory element‐binding protein‐2 messenger ribonucleic acid expression level was significantly decreased at night in anagliptin‐treated mice (15% reduction, P < 0.05). Anagliptin significantly suppressed sterol regulatory element‐binding protein activity in HepG2 cells (21% decrease, P < 0.001).ConclusionsThe results presented here showed that the dipeptidyl peptidase‐4 inhibitor, anagliptin, exhibited a lipid‐lowering effect in a hyperlipidemic animal model, and suggested that the downregulation of hepatic lipid synthesis was involved in the effect. Anagliptin might have beneficial effects on lipid metabolism in addition to a glucose‐lowering effect.
Challenges to the validity of using medicine labels to categorize clinical behavior: An empirical and normative critique of “off‐label” prescribing
Authors: Ghinea Narcyz , Kerridge Ian , Little Miles , Lipworth Wendy 
Published: November 2016

AbstractThis study aimed to determine whether the label status of a medicine penetrates into the clinical reasoning of Australian medical practitioners and to explore the possible reasons for our findings using semistructured interviews with 14 Australian physicians. The interviews revealed 3 broad catalysts for off‐label prescribing. The first of these was lack of awareness or understanding of the regulatory process in general and labels more specifically. The second was the perception that labels are not meaningful guides for clinical practice. The third was the recognition of alternative mechanisms for ensuring safe, rational, and evidence‐based prescribing occurs. This research suggests that Australian physicians do not consider whether a medicine is off‐label to be a reliable measure of the appropriateness of their prescribing practices. Rather, the legitimacy of prescribing practices is determined by the abilities, skills, and knowledge base of particular prescribers by a culture that encourages and supports evidence‐based practice, and safe prescribing. Although labels are of minimal clinical significance, there are real conceptual, practical, and moral problems associated with conflating “good” or “better” practice with “on‐label” practice, and “bad” or “worse” practice with off‐label prescribing as often occurs. To ascribe greater meaning to the term “off‐label” than is warranted can have the unintended consequence of casting suspicion on and making it more difficult for physicians to provide appropriate clinical care. We conclude that labeling can, in some cases, provide assurances to both clinicians and patients that their medications have been demonstrated to be safe and effective, but that clinicians should be able to continue to prescribe responsibly off‐label without having any stigma attached to their practice.
External validation of the non‐alcoholic fatty liver disease fibrosis score for assessing advanced fibrosis in Korean patients
Authors: Jun Dae Won , Kim Sang Gyune , Park Sang Hoon , Jin So‐Young , Lee Ji Sung , Lee Jin‐Woo , Kim Moon Young , Choi Dae Hee , Cho Yong Kyun , Yeon Jong Eun , Sohn Joo Hyun ,   Korean NAFLD study group (KNSG)
Published: November 2016

AbstractBackgroundThe degree of liver fibrosis in non‐alcoholic fatty liver disease (NAFLD) is a critical predictive factor for patient prognosis. This study was intended to perform external validation of the various fibrosis prediction models for assessing advanced fibrosis in Korean NAFLD patients.MethodsA retrospective study of 412 patients with NAFLD confirmed by liver biopsy in hospitals affiliated with the Koran NAFLD study group was conducted and the predictive ability of existing liver fibrosis prediction models including NAFLD fibrosis score (NFS), BARD, and fibrosis‐4 were compared.ResultsAmong 412 samples, 328 liver slides were suitable for evaluation. Advanced fibrosis was present in 60 (18.3%) of the patient samples. Univariate analysis found that the group with advanced fibrosis showed low alanine aminotransferase values and high aspartate aminotransferase/alanine aminotransferase ratios as well as a high incidence of diabetes. However, multivariate analysis showed that only the presence of diabetes and triglycerides was independent risk factors. The receiver operating characteristic was 0.64 in NFS, 0.58 in fibrosis‐4, and 0.594 in the BARD model. The NFS was found to be the best at predicting advanced fibrosis among the three prediction models. The negative predictive value which predicts advanced fibrosis using the low cutoff (<−1.455) was high (86.6%). However, the positive predictive value which predicts advanced fibrosis using the high cutoff (>0.676) was 50.0% when we applied the NFS.ConclusionNegative predictive value using the low cutoff value was high, but positive predictive value using the high cutoff value was low in a Korean NAFLD cohort using NFS.
Psychometric properties of the AIR Self‐Determination Scale: the Chinese version (AIR SDS‐C) for Chinese people with intellectual disabilities
Authors: Wong P. K. S. , Wong D. F. K. , Zhuang X. Y. , Liu Y. 
Published: November 2016

AbstractBackgroundThe construct of self‐determination has received considerable attention in the international field of intellectual disabilities (ID). Recently, there has been a rapid development of this construct in Chinese societies including Hong Kong. However, there is no locally validated instrument to measure self‐determination in people with ID. This article explains the validation process of the AIR Self‐Determination Scale – Chinese version (AIR SDS‐C) adapted from the 24‐item AIR Self‐Determination Scale, developed by Wolman and his colleagues, which is used in school setting.MethodsPeople with mild/moderate ID aged 15 years or above were recruited from special schools and social services units in different regions of Hong Kong. Factor analysis and reliability tests were conducted.ResultsData for a total of 356 participants were used for the analysis. A confirmatory factor analysis was performed to test the factorial construct, and Mplus 7.0 was used for the analysis. The factor structure proposed in the original English version was supported by the data, and all factor loadings were between 0.42 and 0.76. The whole scale achieved good reliability (Cronbach's α = 0.88 and ω = 0.90).ConclusionsThe AIR SDS‐C appears to be a valid and reliable scale. This study examined adult groups as well as student groups. The application of the scale can thus be extended to a wider population. The implications for theory building and practice are discussed.
Immunohistochemical expression of podoplanin (D2‐40), lymphangiogenesis, and neoangiogenesis in tooth germ, ameloblastomas, and ameloblastic carcinomas
Authors: Sánchez‐Romero Celeste , Bologna‐Molina Ronell , Mosqueda‐Taylor Adalberto , de Almeida Oslei Paes 
Published: November 2016

BackgroundAmeloblastoma is a benign but locally aggressive odontogenic tumor, while ameloblastic carcinoma is its malignant counterpart. Angiogenesis and lymphangiogenesis in malignancies have been correlated with higher aggressiveness and poor prognosis, as well as greater expression of podoplanin by tumoral cells.MethodsImmunohistochemical expression of podoplanin, CD34, and CD105 (endoglin) was evaluated in 53 ameloblastomas and three ameloblastic carcinomas; additionally, immunohistochemistry for podoplanin was also performed in 10 tooth germs. Microvessel density of blood and lymphatic vessels was calculated and compared between ameloblastomas and ameloblastic carcinomas. Immunoexpression of podoplanin by ameloblastic cells was evaluated in tooth germs, ameloblastomas, and ameloblastic carcinomas.ResultsPodoplanin was similarly expressed by odontogenic epithelial cells of tooth germs and ameloblastomas, while its expression was lower in ameloblastic carcinomas. There was no difference in microvessel density assessed by CD34 between ameloblastomas and ameloblastic carcinomas; nevertheless, the latter presented higher amounts of lymphatic and new formed blood vessels.ConclusionsResults suggest that podoplanin does not seem to be involved in invasion mechanisms of ameloblastic carcinomas, as its expression was decreased in the malignant tumoral cells. On the other hand, the increased lymphatic microvessel density and neoangiogenesis found in ameloblastic carcinomas could be related to its aggressiveness and potential for metastasis.
Effects of localized interactions and surface properties on stability of protein-based therapeutics
Authors: Mills Brittney J , Laurence Chadwick Jennifer S 
Published: November 2016

Abstract

Objectives
Protein-based therapeutics garner significant attention because of exquisite specificity and limited side effects and are now being used to accomplish targeted delivery of small-molecule drugs. This review identifies and highlights individual chemical attributes and categorizes how site-specific changes affect protein stability based on published high-resolution molecular analyses.

Key findings
Because it is challenging to determine the mechanisms by which the stability of large, complex molecules is altered and data are sparse, smaller, therapeutic proteins (insulin, erythropoietin, interferons) are examined alongside antibody data. Integrating this large pool of information with the limited available studies on antibodies reveals common mechanisms by which specific alterations affect protein structure and stability.

Summary
Physical and chemical stability of therapeutic proteins and antibody drug conjugates (ADCs) is of critical importance because insufficient stability prevents molecules from making it to market. Individual moieties on/near the surface of proteins have substantial influence on structure and stability. Seemingly small, superficial modification may have far-reaching consequences on structure, conformational dynamics, and solubility of the protein, and hence physical stability of the molecule. Chemical modifications, whether spontaneous (e.g. oxidation, deamidation) or intentional, as with ADCs, may adversely impact stability by disrupting local surface properties or higher order protein structure.
Abiotic influences on bicarbonate use in the giant kelp, Macrocystis pyrifera, in the Monterey Bay
Authors: Drobnitch Sarah Tepler , Nickols Kerry , Edwards Matthew 
Published: November 2016

In the Monterey Bay region of central California, the giant kelp Macrocystis pyrifera experiences broad fluctuations in wave forces, temperature, light availability, nutrient availability, and seawater carbonate chemistry, all of which may impact their productivity. In particular, current velocities and light intensity may strongly regulate the supply and demand of inorganic carbon (Ci) as substrates for photosynthesis. Macrocystis pyrifera can acquire and utilize both CO2 and bicarbonate (HCO3−) as Ci substrates for photosynthesis and growth. Given the variability in carbon delivery (due to current velocities and varying [DIC]) and demand (in the form of saturating irradiance), we hypothesized that the proportion of CO2 and bicarbonate utilized is not constant for M. pyrifera, but a variable function of their fluctuating environment. We further hypothesized that populations acclimated to different wave exposure and irradiance habitats would display different patterns of bicarbonate uptake. To test these hypotheses, we carried out oxygen evolution trials in the laboratory to measure the proportion of bicarbonate utilized by M. pyrifera via external CA under an orthogonal cross of velocity, irradiance, and acclimation treatments. Our Monterey Bay populations of M. pyrifera exhibited proportionally higher external bicarbonate utilization in high irradiance and high flow velocity conditions than in sub‐saturating irradiance or low flow velocity conditions. However, there was no significant difference in proportional bicarbonate use between deep blades and canopy blades, nor between individuals from wave‐exposed versus wave‐protected sites. This study contributes a new field‐oriented perspective on the abiotic controls of carbon utilization physiology in macroalgae.
Grazing and temporal turnover in herbaceous communities in a Mediterranean landscape
Authors: Bar‐Massada Avi , Hadar Liat 
Published: November 2016

AbstractQuestionWhat are the direct and indirect effects of cattle grazing on temporal turnover in Mediterranean herbaceous communities, and are there differences between species (taxonomic) and functional turnover rates? Are turnover rates related to changes in precipitation patterns?LocationThe long term ecological research (LTER) station, Ramat Hanadiv Nature Park, Israel.MethodsWe used data from a Mediterranean LTER site to analyse temporal turnover in herbaceous communities under cattle grazing and control conditions, while accounting for the potential effects of precipitation and woody cover. We analysed two types of temporal turnover: taxonomic turnover (changes in species composition) and turnover in functional traits (changes in the relative abundance of species with different functional traits).ResultsWe found that communities exhibited rapid taxonomic turnover between sampling years, which was mostly explained by changes in precipitation patterns. Furthermore, there was a strong and consistent directional trend in taxonomic turnover (21% per decade) throughout the study period, which was correlated with a long‐term trend of decreasing precipitation. This trend, however, was not significantly explained by grazing, woody cover change or their interaction. Grazing did have a significant effect on short‐term turnover rates, but its effects varied in both direction and magnitude among sites located in different habitats. Temporal turnover in functional traits was much slower than taxonomic turnover, and was also inconsistent among traits and sites. Grazing reduced the bi‐annual turnover rates in the composition of different life forms, and reduced the decadal turnover rate in the composition of different height groups in the community.ConclusionsThe results of this analysis suggest that the effect of cattle grazing on the temporal dynamics of herbaceous communities in Mediterranean ecosystems is habitat‐ and trait‐specific, and unrelated to changes in woody cover. In contrast, inter‐annual changes in precipitation patterns have a much stronger effect on turnover rates. The relationship between temporal species turnover and precipitation in these communities is therefore in line with modern co‐existence theory, by which fluctuating environmental conditions facilitate long‐term species co‐existence.
The emotional and practical experiences of formula‐feeding mothers
Authors: Fallon Victoria , Komninou Sophia , Bennett Kate M. , Halford Jason C.G. , Harrold Joanne A. 
Published: November 2016

AbstractThe majority of infant‐feeding research is focused on identifying mother's reasons for the cessation of breastfeeding. The experience of mothers who choose to use formula is largely overlooked in quantitative designs. This study aimed to describe the emotional and practical experiences of mothers who formula feed in any quantity, and examine whether these experiences would vary among different cohorts of formula‐feeding mothers according to prenatal feeding intention and postnatal feeding method. A total of 890 mothers of infants up to 26 weeks of age, who were currently formula feeding in any quantity, were recruited through relevant international social media sites via advertisements providing a link to an online survey. Predictors of emotional experiences included guilt, stigma, satisfaction, and defense as a result of their infant feeding choices. Practical predictor variables included support received from health professionals, respect displayed by their everyday environment, and main sources of infant feeding information. Descriptive findings from the overall sample highlighted a worryingly high percentage of mother's experienced negative emotions as a result of their decision to use formula. Multinomial logit models revealed that negative emotions such as guilt, dissatisfaction, and stigma were directly associated with feeding intention and method. The evidence suggests that the current approach to infant‐feeding promotion and support may be paradoxically related to significant issues with emotional well‐being. These findings support criticisms of how infant‐feeding recommendations are framed by health care professionals and policy makers, and highlight a need to address formula feeding in a more balanced, woman‐centered manner.
Prevalence of keds on city dogs in central Poland
Authors: SOKÓŁ R. , GAŁĘCKI R. 
Published: November 2016

AbstractThe aim of this study was to identify the species of ked infesting dogs in the cities of central Poland. A total of 510 dogs were observed between June and September 2015. The presence of keds was noted in 182 (35.7%) animals. Keds were more prevalent in female (38.0%) than in male (33.2%) dogs, and were more frequently found in animals younger than 1 year (46.2%) and in long‐haired dogs (36.6%). The body areas most heavily colonized by keds were the groin (35.4%) and neck (21.4%). A total of 904 keds were isolated from dogs, including Hippobosca equina (Diptera: Hippoboscidae) (17.2%), Lipoptena cervi (Diptera: Hippoboscidae) (32.0%), and two species not previously encountered in Poland: Hippobosca longipennis (45.0%) and Lipoptena fortisetosa (5.9%). Hippoboscidae may act as vectors of pathogens and any shifts in their geographic range may lead to the spread of new diseases affecting animals.
Second premolar agenesis as a subclinical phenotype of isolated cleft palate
Authors: Schwartz J. P. , Lauris R. C. M. C. , Dalbén G. , Garib D. G. 
Published: November 2016

Structured AbstractObjectiveTo compare the prevalence of dental anomalies in patients with isolated cleft palate with or without hypodontia of the second premolar.Setting and Sample PopulationA total of 653 patients with isolated cleft palate aged 8–12 years were divided into two groups: G1—subjects without hypodontia of second premolar (n = 546) and G2—subjects with hypodontia of at least one‐second premolar (n = 107). The control group consisted of 107 non‐cleft orthodontic patients.Materials & MethodsPanoramic and periapical radiographs and dental casts were used to analyze the presence of dental anomalies. Intergroup comparisons were performed using the chi‐square test complemented by Proportion test and Bonferroni test.ResultsG2 presented higher prevalence of hypodontia of other permanent teeth compared to G1 and control. Ectopic eruption of the maxillary canine and tooth transposition were more frequent in patients with a cleft compared to patients without a cleft, without statistical differences. Deciduous molar infra‐occlusion and second premolar disto‐angulation were less prevalent in G1 and G2 compared to the control group. G2 showed a higher prevalence of complete cleft palate than G1.ConclusionPatients with cleft palate and second premolar agenesis showed increased prevalence of tooth agenesis and palatally displaced canines.
Generation of marker‐free transgenic hexaploid wheat via an Agrobacterium‐mediated co‐transformation strategy in commercial Chinese wheat varieties
Authors: Wang Ke , Liu Huiyun , Du Lipu , Ye Xingguo 
Published: November 2016

SummaryGenotype specificity is a big problem lagging the development of efficient hexaploid wheat transformation system. Increasingly, the biosecurity of genetically modified organisms is garnering public attention, so the generation of marker‐free transgenic plants is very important to the eventual potential commercial release of transgenic wheat. In this study, 15 commercial Chinese hexaploid wheat varieties were successfully transformed via an Agrobacterium‐mediated method, with efficiency of up to 37.7%, as confirmed by the use of Quickstix strips, histochemical staining, PCR analysis and Southern blotting. Of particular interest, marker‐free transgenic wheat plants from various commercial Chinese varieties and their F1 hybrids were successfully obtained for the first time, with a frequency of 4.3%, using a plasmid harbouring two independent T‐DNA regions. The average co‐integration frequency of the gus and the bar genes located on the two independent T‐DNA regions was 49.0% in T0 plants. We further found that the efficiency of generating marker‐free plants was related to the number of bar gene copies integrated in the genome. Marker‐free transgenic wheat plants were identified in the progeny of three transgenic lines that had only one or two bar gene copies. Moreover, silencing of the bar gene was detected in 30.7% of T1 positive plants, but the gus gene was never found to be silenced in T1 plants. Bisulphite genomic sequencing suggested that DNA methylation in the 35S promoter of the bar gene regulatory region might be the main reason for bar gene silencing in the transgenic plants.
Leptomeningeal dissemination and vertebral bone involvement in a child with pilocytic astrocytoma
Authors: Demirkaya Metin , Sevinir Betül , Güler Salih , Demiröz Candan , Taskapilioglu Özgür , Yilmazlar Selcuk , Palabiyik Figen , Tolunay Sahsine 
Published: November 2016

AbstractIn low‐grade glioma, metastasis is rarely seen. Few cases of leptomeningeal dissemination have been reported in children. Vertebral bone metastasis has not been reported so far. Herein is described the case of a pediatric patient with the diagnosis of pilocytic astrocytoma, and leptomeningeal dissemination detected at the time of diagnosis, who then received radiotherapy and chemotherapy upon development of vertebral bone metastasis during treatment.