bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence‐based HMO care for prostate specific antigen testing
Authors: Merenstein Daniel J. , D'Amico Frank J. , Vinker Shlomo , Petterson Stephen , Lahad Amnon 
Published: September 2016

SummaryBackgroundThere is pressure in the U.S. system to move away from fee‐for‐service models to a more pre‐paid system, which may result in decreased costs, but the impact on evidence‐based care is unclear. We examined a large pre‐paid Health Maintenance Organizations (HMO) in Israel to see if evidence‐based guidelines are followed for prostate specific antigen (PSA) testing.MethodsA retrospective cohort of ambulatory visits from 2002 to 2011 of patients age >75 receiving care from Clalit Health Services was conducted. Historically reported U.S. cohorts were used for comparison. The main measure was the percent of patients who had at least one PSA after age 75.ResultsIn each of the 10 years of follow‐up, 22% of the yearly Israeli cohort, with no known malignancy or benign prostatic hyperplasia, had at least one PSA, while for the total 10 years, 30% of the men had at least one PSA. These rates are considerably lower than previously reported U.S. rates.ConclusionsIn a pre‐paid system in which physicians have no incentive to order tests, they appear to order PSA tests at a lower rate than has been observed in the U.S. system. Additional quality of measures should continue to be examined as the U.S. shifts away from a fee‐for‐service model. Copyright © 2016 John Wiley & Sons, Ltd.
The Fluorine Gauche Effect: A Brief History
Authors: Thiehoff Christian , Rey Yannick P. , Gilmour Ryan 
Published: September 2016

AbstractTransforming the fluorine gauche effect from an academic curiosity into a powerful acyclic conformational control strategy has enriched molecular design. This expansive approach to modulating structure has proven to be particularly valuable in the construction of functional small molecules, thereby finding application in diverse disciplines, ranging from therapeutic medicine to enantioselective catalysis. In contrast to the well‐established arsenal of conformational control tactics, in which conformer populations result from minimising nonbonding interactions, (e.g., A1,3‐ or A1,2‐strain), the fluorine gauche effect is attributable to stabilising interactions comprised of two components: stereoelectronic and electrostatic. Conformer populations are partially determined by favourable, hyperconjugative interactions involving proximal electron‐rich σ‐bonds, π‐systems, and nonbonding electron pairs with the antibonding orbital of the C−F σ‐bond: σ→σ*, π→σ*, and n→σ*, respectively. Electrostatic, charge‐dipole interactions (e.g., N+⋅⋅⋅Fδ−) also play a crucial role in stabilising what are often counter‐intuitive conformations. These noncovalent interactions, permissible on account of the low van der Waals radius and high electronegativity of the fluorine atom, render this effect fundamentally important and practically valuable in structural chemistry. In this contribution to the Rosarium Philosophorum in honour of Prof. Jack David Dunitz FRS, we endeavour to delineate, albeit in an abridged form, the evolution of the fluorine gauche effect from a fundamental spectroscopic study to a ubiquitous component of physical organic chemistry.
RGDfK‐functionalized gold nanorods bind only to activated platelets
Authors: Zeller Meidell Krystin , Robinson Ryan , Vieira‐de‐Abreu Adriana , Gormley Adam J. , Ghandehari Hamidreza , W. Grainger David , A. Campbell Robert 
Published: September 2016

AbstractIntegrin‐targeting peptide RGDfK‐labeled gold nanorods (GNR) seek to improve hyperthermia targeted to solid tumors by exploiting the known up‐regulation of integrin αvβ3 cell membrane proteins on solid tumor vasculature surfaces. Tumor binding specificity might be expected since surrounding tissues and endothelial cells have limited numbers of these receptors. However, RGD peptide binding to many proteins is promiscuous, with known affinity to several families of cell integrin receptors, and also possible binding to platelets after intravenous infusion via a different integrin receptor, αIIbβ3, on platelets. Binding of RGDfK‐targeted GNR could considerably impact platelet function, ultimately leading to increased risk of bleeding or thrombosis depending on the degree of interaction. We sought to determine if RGDfK‐labeled GNR could interact with platelets and alter platelet function. Targeted and untargeted nanorods exhibited little interaction with resting platelets in platelet rich plasma (PRP) preparations. However, upon platelet activation, peptide‐targeted nanorods bound actively to platelets. Addition of RGDfK‐GNR to unactivated platelets had little effect on markers of platelet activation, indicating that RGDfK‐nanorods were incapable of inducing platelet activation. We next tested whether activated platelet function was altered in the presence of peptide‐targeted nanorods. Platelet aggregation in whole blood and PRP in the presence of targeted nanorods had no significant effect on platelet aggregation. These data suggest that RGDfK‐GNR alone have little impact on platelet function in plasma. However, nonspecific nanorod binding may occur in vascular beds where activated platelets are normally cleared, such as the spleen and liver, producing a possible toxicity risk for these nanomaterials. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 209–217, 2017.
Correlations Between Bone Mechanical Properties and Bone Composition Parameters in Mouse Models of Dominant and Recessive Osteogenesis Imperfecta and the Response to Anti-TGF-β Treatment
Authors: Bi Xiaohong , Grafe Ingo , Ding Hao , Flores Rene , Munivez Elda , Jiang Ming Ming , Dawson Brian , Lee Brendan , Ambrose Catherine G 
Published: September 2016

ABSTRACT

Osteogenesis imperfecta (OI) is a group of genetic disorders characterized by brittle bones that are prone to fracture. Although previous studies in animal models investigated the mechanical properties and material composition of OI bone, little work has been conducted to statistically correlate these parameters to identify key compositional contributors to the impaired bone mechanical behaviors in OI. Further, although increased TGF-β signaling has been demonstrated as a contributing mechanism to the bone pathology in OI models, the relationship between mechanical properties and bone composition after anti-TGF-β treatment in OI has not been studied. Here, we performed follow-up analyses of femurs collected in an earlier study from OI mice with and without anti-TGF-β treatment from both recessive (Crtap-/-) and dominant (Col1a2+/P.G610C) OI mouse models and WT mice. Mechanical properties were determined using three-point bending tests and evaluated for statistical correlation with molecular composition in bone tissue assessed by Raman spectroscopy. Statistical regression analysis was conducted to determine significant compositional determinants of mechanical integrity. Interestingly, we found differences in the relationships between bone composition and mechanical properties and in the response to anti-TGF-β treatment. Femurs of both OI models exhibited increased brittleness, which was associated with reduced collagen content and carbonate substitution. In the Col1a2+/P.G610C femurs, reduced hydroxyapatite crystallinity was also found to be associated with increased brittleness, and increased mineral-to-collagen ratio was correlated with increased ultimate strength, elastic modulus, and bone brittleness. In both models of OI, regression analysis demonstrated that collagen content was an important predictor of the increased brittleness. In summary, this work provides new insights into the relationships between bone composition and material properties in models of OI, identifies key bone compositional parameters that correlate with the impaired mechanical integrity of OI bone, and explores the effects of anti-TGF-β treatment on bone-quality parameters in these models. © 2016 American Society for Bone and Mineral Research.
Carbon‐14 radiolabeling and tissue distribution evaluation of MMV390048
Authors: Sonopo Molahlehi S. , Pillay Adushan , Chibale Kelly , Marjanovic‐Painter Biljana , Donini Cristina , Zeevaart Jan R. 
Published: September 2016

The antimalarial compound MMV390048 ([14C]‐11) was labeled with carbon‐14 isotope via a 3‐step synthesis. It was obtained in a 15.5% radiochemical overall yield from carbon‐14 labeled methyl iodide with a radiochemical purity of >99%. After single oral administration of [14C]‐11 to albino and pigmented rats its tissue distribution profile was studied. Tissue distribution results showed high local exposure in the GI tract and excretory organs but low exposure of all other tissues. The radioactivity uptake was higher in the eyes of the pigmented rats than in the eyes of the albino rats at all‐time points. The highest accumulation reached in the eyes of the pigmented rats was 0.46% at 6 hours. However, these levels are still very low as compared to the other organs studied. There was very little radioactivity from MMV390048 ([14C]‐11) present in the skin of both the albino and pigmented rats. The results obtained are supportive of further development of MMV390048 as a potential antimalarial compound.
The ethmoid and presphenoid of cetaceans
Authors: Ichishima Hiroto 
Published: September 2016

ABSTRACTA cribriform plate, a perpendicular plate, and two lateral masses are major components of the ethmoid bone of mammals. Notwithstanding the noticeable bone, virtually sitting in the center of the skull, extensive modifications of the skull of modern cetaceans, especially odontocetes (toothed whales), and the lack of clarity as to what characteristics delimit each element of the ethmoid has made the problem of the nature of the cetacean ethmoid more complicated and elusive than in other, less modified mammals. Furthermore, contention as to whether a perpendicular plate of the ethmoid, or the mesethmoid, exists in all mammals including cetaceans has remained unsettled. In odontocetes, the mesethmoid has been variably identified not only as the osseous nasal septum but also as the mediodorsal region of the posterior wall of the nasal passage below the nasals, as a mass of bone encased by the vomer in front of the osseous nasal cavity at the base of the rostrum, and as a combination of some portions mentioned above. The presence or absence of the mesethmoid in various groups of mammals has attracted the attention of some biologists, and here, I demonstrate that cetaceans have no mesethmoid. The close inspection of the ontogenetic changes of the basicranial elements in cetaceans reveals that a mass of bone ensheathed by the vomer in front, or at the level of the osseous nasal cavity is actually the presphenoid. It is highly likely that in odontocetes the posterior wall of the nasal passages below the nasals consists of the combination of the frontal, the imperforated cribriform plate, the paired ectethmoids, and the vomer, the latter three of which partially concealing the presphenoid dorsally and laterally as the ontogeny proceeds. In contrast, mysticetes clearly display ethmoturbinates and a cribriform plate, which are morphologically similar to those in terrestrial mammals. J. Morphol. 277:1661–1674, 2016. © 2016 Wiley Periodicals, Inc.
Identifying abrupt changes and detecting gradual trends of annual rainfall in an Indian arid region under heightened rainfall rise regime
Authors: Machiwal Deepesh , Kumar Sanjay , Dayal Devi , Mangalassery Shamsudheen 
Published: September 2016

ABSTRACTThis study aimed at identification of abrupt change points (CPs) and detection of gradual trends in 34‐year (1980–2013) annual rainfall at nine stations of an Indian arid region. TheCPswere determined by five tests and their significance was examined by two tests. Furthermore, trends were tested by three tests and their magnitudes were quantified by two tests. Novelty of the study lies in investigating significance of trends sequentially over years by applying Mann–Kendall (M–K) test. The identifiedCPswere similar for standard normal homogeneity test and cumulative deviations test at most stations. In contrast, Pettitt and Bayesian tests detectedCPin years 2002 and 2005 at six and three stations, respectively, and their significance was verified. Results of sequential M–K test did not match with other tests' results. The mean annual rainfall afterCP(350–627 mm) increased by 14–80% of the amount beforeCP(306–444 mm) with 7–42% reduction in coefficient of variation. The box–whisker plots supported these findings. Results of trend tests indicated statistically significant trends at Anjar, Bhachau, Mandvi and Rapar. Trend magnitudes by linear regression prior toCP(−6.2 to 7.1 mm year−1) showed an overall increase afterCP(4.7–40.8 mm year−1) with negative trend at one station. Sen's slope test, showing good harmony with linear regression, revealed that trend magnitudes afterCPwere 2–10 times higher than that for 34‐year period at six stations. Results of M–K test applied for sequential periods emphasized that rainfall trends are becoming stronger over time. This finding suggests that significance level of increasing rainfall trends may further increase in future. Finally, findings of this study are useful for planners and decision makers for developing policies to meet the challenges of the heightened rainfall in study area. Also, the approach used here may be adopted in other parts of the globe.
Responses of spring phenology in a fruit tree species (Pyrus sp. cv. Pingguoli) to the changes in surface air temperature in Northeast China
Authors: Shen Yinyue , Kobayashi Kazuhiko 
Published: September 2016

ABSTRACTWe analysed records of spring phenological events (budding and flowering) of pear (Pyrus sp.) cultivar ‘Pingguoli’ at six sites in the Yanbian District of Jilin Province, northeast China across 58 years from 1953. The aims of this study were to test if the phenological timing in spring has changed due to the long‐term change in surface air temperature and to see if the relationship between the phenological timing and the surface air temperature shows nonlinearity as suggested by a past study. We fitted a linear model of phenological timing as the sum of the effects of long‐term temperature trends and year‐to‐year temperature fluctuations. The results showed that the acceleration of spring phenology can be attributed to the corresponding trends of increasing mean air temperature in spring. The relationship between air temperature and phenological timing was linear for budding, but it was nonlinear for flowering with a lower temperature sensitivity at higher air temperature.
Late Quaternary glacial history of the Nalati Range, central Tian Shan, China, investigated using 10Be surface exposure dating
Authors: Zhang Mei , Chen Yixin , Li Yingkui , Liu Gengnian 
Published: September 2016

ABSTRACTWe constrained glacial chronologies in three valleys on the southern slopes of the Nalati Range in the central Tian Shan, China: the Takelakete, Aiken and Sairenwuxunsala valleys, using 10Be surface exposure dating. Our 10Be exposure ages constrain three glacial events during 72.8 ± 3.8–59.9 ± 3.5 ka, 55.4 ± 3.0–34.9 ± 2.1 and 0.29 ± 0.17–0.27 ± 0.20 ka, corresponding to Marine Oxygen Isotope Stages (MIS) 4 and 3, and Little Ice Age (LIA), respectively. Glaciers have been restricted from composite valley glaciers and piedmont glaciers during MIS 4–3 to confined valley glaciers during MIS 3, to small valley glaciers during the LIA, and to hanging and cirque glaciers at present. This pattern of glacial change is broadly consistent with other glaciated areas across the Tian Shan. Extensive glacial advances during MIS 4 and 3 were probably driven by enhanced precipitation brought by the westerlies. Compared to MIS 3 glacial advance, lower temperature may counteract the effect of relatively lower precipitation to drive a similar or even larger glacial advance during MIS 4. Glacial advances were limited during MIS 2, probably reflecting enhanced arid conditions in the Tian Shan caused by the weakened westerlies and strengthened Siberian High.
Comparison of reduced sugar high quality chocolates sweetened with stevioside and crude stevia ‘green’ extract
Authors: Torri Luisa , Frati Alessandra , Ninfali Paolino , Mantegna Stefano , Cravotto Giancarlo , Morini Gabriella 
Published: September 2016

AbstractBACKGROUNDThe demand for zero and reduced‐sugar food products containing cocoa is expanding continuously. The present study was designed to evaluate the feasibility of producing high‐quality chocolate sweetened with a crude extract of Stevia rebaudiana (Bertoni) prepared by a green microwave‐assisted water‐steam extraction procedure. Seven approximately isosweet chocolate formulations were developed, mixing cocoa paste, sucrose, commercial stevioside, crude green extract and maltitol in different proportions. All samples were analyzed for the determination of polyphenol and flavonoid content, antioxidant activity, and sensory acceptability.RESULTSThe use of a crude stevia extract allowed low‐sugar, high‐quality chocolates to be obtained that were also acceptable by consumers and had a significant increased antioxidant activity. Moreover, consumers' segmentation revealed a cluster of consumers showing the same overall liking for the sample with 50% sucrose replaced by the stevia crude extract as that obtained with the commercial stevioside and the control sample (without sucrose replacement).CONCLUSIONThe results provide information that can contribute to promoting the development of sweet food products, with advantages in terms of an improved nutritional value (reduced sugar content and increased antioxidant activity) and a reduced impact of the production process on the environment. © 2016 Society of Chemical Industry
Trapping Dynamic Disulfide Bonds in the Hard Segments of Thermoplastic Polyurethane Elastomers
Authors: Zhang Longhe , Chen Lifeng , Rowan Stuart J. 
Published: September 2016

Dynamic covalent bonds placed within a polymer chain result in stimulus‐responsive materials where the breaking/making and/or exchange of the dynamic bonds controls the response. A key attribute to access such properties is the molecular mobility of the dynamic bonds. The focus of this work is to understand how incorporating a dynamic bond, in the form of disulfide bonds, into the hard phase of a polyurethane will impact the properties of the materials. Thus, uncross‐linked polyurethanes with aliphatic disulfide‐containing hard segments are synthesized via a two‐step protocol, using 2,2′‐dithiodiethanol and/or 1,4‐butanediol in the second step as the chain extenders. Thermomechanical studies show that, if the dynamic bonds are selectively placed in the hard phase of the polyurethane, the dynamic nature of the disulfide bond can be effectively “switched‐off” below the melting temperature of the hard phase. As such the dynamic and mechanical properties of the materials can be controlled by tailoring the nature of the hard phase.image
RAFT‐Polymerization‐Induced Self‐Assembly and Reorganizations: Ultrahigh‐Molecular‐Weight Polymer and Morphology‐Tunable Micro‐/Nanoparticles in One Pot
Authors: Zhang Xiao‐Yun , Liu Dong‐Ming , Lv Xin‐Hu , Sun Miao , Sun Xiao‐Li , Wan Wen‐Ming 
Published: September 2016

A one‐pot method is introduced for the successful synthesis of narrow‐distributed (Đ = 1.22) vinyl polymer with both ultrahigh molecular weight (UHMW) (M
w = 1.31 × 106 g mol−1) and micro‐/nanomorphology under mild conditions. The method involves the following four stages: homogeneous polymerization, polymerization‐induced self‐assembly (PISA), PISA and reorganization, and PISA and multiple reorganizations. The key points to the production of UHMW polystyrene are to minimize radical termination by segregating radicals in different nanoreactors and to ensure sufficient chain propagation by promoting further reorganizations of these reactors in situ. This method therefore endows polymeric materials with the outstanding properties of both UHMW and tunable micro‐/nanoparticles under mild conditions in one pot.image
Painful Charcot–Marie–Tooth neuropathy type 2E/1F due to a novel NEFL mutation
Authors: Doppler Kathrin , Kunstmann Erdmute , Krüger Stefan , Sommer Claudia 
Published: September 2016

ABSTRACTIntroductionCharcot–Marie–Tooth neuropathy (CMT) 2E/1F is caused by mutations in the neurofilament light‐chain polypeptide (NEFL) gene. Giant axons are a histological hallmark frequently seen in nerves of patients with CMT2E.MethodsWe describe the case of a 43‐year‐old patient with a painful, predominantly sensory neuropathy.ResultsThe patient's sural nerve biopsy showed multiple giant axons. Genetic sequencing of the NEFL gene revealed that the patient was heterozygous for an altered sequence of the gene, c.816C>G, p.Asn272Lys, which has not yet been described in CMT2E/1F.ConclusionIn contrast to other cases of CMT2E/1F, where motor symptoms are predominant, pain was the most disabling symptom in this patient. Muscle Nerve 55: 752–755, 2017
A GWAS follow‐up of obesity‐related SNPs in SYPL2 reveals sex‐specific association with hip circumference
Authors: de Toro‐Martín J. , Guénard F. , Tchernof A. , Deshaies Y. , Pérusse L. , Biron S. , Lescelleur O. , Biertho L. , Marceau S. , Vohl M.‐C. 
Published: September 2016

SummaryObjectiveA novel single‐nucleotide polymorphism (SNP) associated with morbid obesity was recently identified by exome sequencing. The purpose of this study was to follow up this low‐frequency coding SNP located within the SYPL2 locus and associated with body mass index in order to reveal novel associations with obesity‐related traits.MethodsThe body mass index‐associated SNP (rs62623713 A>G [chr1:109476817/hg19]) and two tagging SNPs within the SYPL2 locus, rs9661614 T>C (chr1:109479215) and rs485660 G>A (chr1:109480810), were genotyped in the obesity (n = 3,017) and the infogene (n = 676) cohorts, which were further combined, leading to a larger cohort of 3,693 individuals. Association testing was performed by general linear models in the obesity cohort and validated by joint analysis in the combined cohort.Resultsrs9661614 and rs485660 were significantly associated with hip circumference (HC) in the obesity cohort, with heterozygotes exhibiting a significantly lower HC. These results were validated by joint analysis for rs9661614 (false discovery rate [FDR]‐corrected P = 7.5 × 10−4) and, to a lesser extent, for rs485660 (FDR corrected P = 3.9 × 10−2). The association with HC remained significant for rs9661614 when tested independently in women (FDR‐corrected P = 1.7 × 10−2), but not for rs485660 (FDR‐corrected P = 0.2). Both associations were absent in men.ConclusionsThis study reveals strong evidence for a novel association between rs9661614 (T>C) and HC in women, which likely reflects a preferential association of SYPL2 to a gynoid profile of fat distribution. The study findings support a clinical significance of SYPL2 worth considering when assessing risk factors associated with obesity.