bluuebunny/crossref_metadata_2025_split huggingface dataset:
Primary care provider approaches to preventive health delivery: a qualitative study
Authors: Murugan Hemalatha , Spigner Clarence , McKinney Christy M. , Wong Christopher J. 
Published: January 2018

AimThe objective of this study was to seek decision-making insights on the provider level to gain understanding of the values that shape how providers deliver preventive health in the primary care setting.BackgroundThe primary care clinic is a core site for preventive health delivery. While many studies have identified barriers to preventive health, less is known regarding how primary care providers (PCPs) make preventive health decisions such as what services to provide, under what circumstances, and why they might choose one over another.MethodsQualitative methods were chosen to deeply explore these issues. We conducted semi-structured, one-on-one interviews with 21 PCPs at clinics affiliated with an academic medical center. Interviews with providers were recorded and transcribed. We conducted a qualitative analysis to identify themes and develop a theoretical framework using Grounded Theory methods.FindingsThe following themes were revealed: longitudinal care with an established PCP–patient relationship is perceived as integral to preventive health; conflict and doubt accompany non-preventive visits; PCPs defer preventive health for pragmatic reasons; when preventive health is addressed, providers use multiple contextual factors to decide which interventions are discussed; and PCPs desired team-based preventive health delivery, but wish to maintain their role when shared decision-making is required. We present a conceptual framework called Pragmatic Deferral.
MATHEMATICAL INFERENCE AND LOGICAL INFERENCE
Authors: HAMAMI YACIN 
Published: January 2018

AbstractThe deviation ofmathematical proof—proof in mathematical practice—from the ideal offormal proof—proof in formal logic—has led many philosophers of mathematics to reconsider the commonly accepted view according to which the notion of formal proof provides an accurate descriptive account of mathematical proof. This, in turn, has motivated a search for alternative accounts of mathematical proof purporting to be more faithful to the reality of mathematical practice. Yet, in order to develop and evaluate such alternative accounts, it appears as a necessary prerequisite to first possess a clear picture of what the deviation of mathematical proof from formal proof consists in. The present work aims to contribute building such a picture by investigating the relation between the elementary steps of deduction constituting the two types of proofs—mathematical inferenceandlogical inference. Many claims have been made in the literature regarding the relation between mathematical inference and logical inference, most of them stating that the former is lacking properties that are constitutive of the latter. Suchdifferentiating claimsare, however, usually put forward without a clear conception of the properties occurring in them, and are generally considered to be immediately justified by our direct acquaintance, or phenomenological experience, with the two types of inferences. The present study purports to advance our understanding of the relation between mathematical inference and logical inference by developing a detailed philosophical analysis of the differentiating claims, that is, an analysis of themeaningof the differentiating claims—through the properties that occur in them—as well as thereasonsthat support them. To this end, we provide at the outset a representative list of the different properties of logical inference that have occurred in the differentiating claims, and we notice that they all boil down to the three properties offormality,generality, andmechanicality. For each one of these properties, our analysis proceeds in two steps: we first provide precise conceptual characterizations of the different ways logical inference has been said to be formal, general, and mechanical, in the philosophical and logical literature on formal proof; we then examine why mathematical inference does not appear to be formal, general, and mechanical, for the different variations of these notions identified. Our study results in a precise conceptual apparatus for expressing and discussing the properties differentiating mathematical inference from logical inference, and provides a first inventory of the various reasons supporting the observations of those differences. The differentiating claims constitute thus a set of data that any philosophical account of mathematical inference and proof purporting to be more faithful to mathematical practice ought to be able to accommodate and explain.
New material of Sigmaboilus (Insecta, Orthoptera, Prophalangopsidae) from the Jurassic Daohugou Beds, Inner Mongolia, China
Authors: Wang He , Fang Yan , Zhang Qingqing , Lei Xiaojie , Wang Bo , Jarzembowski Edmund A. , Zhang Haichun 
Published: January 2018

ABSTRACTFive orthopteran specimens from the uppermost Middle–lowermost Upper Jurassic of Daohugou, Inner Mongolia, China are described and attributed to the genus Sigmaboilus Fang, Zhang & Wang, 2007 (Prophalangopsidae); and a new species, S. calophlebius sp. nov., is established herein. The diagnostic characters for Sigmaboilus are revised and a key to species of Sigmaboilus, based on male forewings, is provided. Intraspecific variation in forewings of this genus is also discussed.
Hippocampal metabolic differences implicate distinctions between physical and psychological stress in four rat models of depression
Authors: Liu Lanxiang , Zhou Xinyu , Zhang Yuqing , Pu Juncai , Yang Lining , Yuan Shuai , Zhao Libo , Zhou Chanjun , Zhang Hanping , Xie Peng 
Published: January 2018

AbstractMajor depressive disorder (MDD) is a heterogeneous and multi-factorial disorder, and the underlying molecular mechanisms remain largely unknown. However, many studies have indicated that the molecular mechanisms underlying depression in response to different stress may differ. After screening, 28–30 rats were included in each model of depression (chronic unpredictable mild stress (CUMS); learned helplessness (LH); chronic restraint stress (CRS); or social defeat (SD)). Non-targeted gas chromatography-mass spectrometry was used to profile the metabolic changes in the hippocampus. As a result, all four models exhibited significant depression-like behavior. A total of 30, 24, 19, and 25 differential metabolites were identified in the CUMS, LH, CRS, and SD models, respectively. Interestingly, the hierarchical clustering results revealed two patterns of metabolic changes that are characteristic of the response to cluster 1 (CUMS, LH) and cluster 2 (CRS, SD) stress, which represent physical and psychological stress, respectively. Bioinformatic analysis suggested that physical stress was mainly associated with lipid metabolism and glutamate metabolism, whereas psychological stress was related to cell signaling, cellular proliferation, and neurodevelopment, suggesting the molecular changes induced by physical and psychological stress were different. Nine shared metabolites were opposite in the directions of change between physical and psychological models, and these metabolites were associated with cellular proliferation and neurodevelopment functions, indicating the response to physical and psychological stress was different in the activation and deactivation of the final common pathway to depression. Our results provide a further understanding of the heterogeneity in the molecular mechanisms of MDD that could facilitate the development of personalized medicine for this disorder.
Corticotropin-releasing factor 1 receptor haplotype and cognitive features of major depression
Authors: Davis Elena Goetz , Keller Jennifer , Hallmayer Joachim , Pankow Heather Ryan , Murphy Greer M. , Gotlib Ian H. , Schatzberg Alan F. 
Published: January 2018

AbstractCorticotropin-releasing factor signaling through CRF receptor type 1 (CRF1) has been shown to contribute to learning and memory function. A haplotype of alleles T-A-T in a set of common polymorphisms in the gene encoding for CRF1(CRHR1) has been associated with both depression vulnerability and alterations in cognitive functioning. The present study investigated the relations between the TAT haplotype and specific symptoms of depression, self-reported ruminative behaviors, and neuropsychological performance on a learning and memory task. Participants were adults with major depression with and without psychotic features (N = 406). Associations were examined between TAT haplotype and endorsement of depression symptoms from diagnostic interviews, scores on the rumination response scale (RRS), and verbal memory performance on the California Verbal Learning Test-II (CVLT-II). All analyses included depression subtype, age, and sex as covariates; CVLT-II analyses also included evening cortisol levels. Across the entire sample, carriers of more copies of the TAT haplotype reported greater endorsement of the symptom describing difficulty concentrating and making decisions. In separate subsamples, TAT homozygotes had higher rumination scores on the RRS, both brooding and reflection subscales, and more TAT copies were associated with poorer CVLT-II performance in both total learning and free recall trials. These data demonstrate that theCRHR1TAT haplotype is associated with cognitive features of depression including difficulty with decision-making, higher rumination, and poorer learning and memory. It will be important in future research to identify the specific molecular mechanisms for CRF1signaling that contribute to depression-related cognitive dysfunction.
TUFT1 interacts with RABGAP1 and regulates mTORC1 signaling
Authors: Kawasaki Natsumi , Isogaya Kazunobu , Dan Shingo , Yamori Takao , Takano Hiroshi , Yao Ryoji , Morishita Yasuyuki , Taguchi Luna , Morikawa Masato , Heldin Carl-Henrik , Noda Tetsuo , Ehata Shogo , Miyazono Kohei , Koinuma Daizo 
Published: January 2018

AbstractThe mammalian target of rapamycin (mTOR) pathway is commonly activated in human cancers. The activity of mTOR complex 1 (mTORC1) signaling is supported by the intracellular positioning of cellular compartments and vesicle trafficking, regulated by Rab GTPases. Here we showed that tuftelin 1 (TUFT1) was involved in the activation of mTORC1 through modulating the Rab GTPase-regulated process. TUFT1 promoted tumor growth and metastasis. Consistently, the expression of TUFT1 correlated with poor prognosis in lung, breast and gastric cancers. Mechanistically, TUFT1 physically interacted with RABGAP1, thereby modulating intracellular lysosomal positioning and vesicular trafficking, and promoted mTORC1 signaling. In addition, expression of TUFT1 predicted sensitivity to perifosine, an alkylphospholipid that alters the composition of lipid rafts. Perifosine treatment altered the positioning and trafficking of cellular compartments to inhibit mTORC1. Our observations indicate that TUFT1 is a key regulator of the mTORC1 pathway and suggest that it is a promising therapeutic target or a biomarker for tumor progression.
Structural insights into two distinct binding modules for Lys63-linked polyubiquitin chains in RNF168
Authors: Takahashi Tomio S. , Hirade Yoshihiro , Toma Aya , Sato Yusuke , Yamagata Atsushi , Goto-Ito Sakurako , Tomita Akiko , Nakada Shinichiro , Fukai Shuya 
Published: January 2018

AbstractThe E3 ubiquitin (Ub) ligase RNF168 plays a critical role in the initiation of the DNA damage response to double-strand breaks (DSBs). The recruitment of RNF168 by ubiquitylated targets involves two distinct regions, Ub-dependent DSB recruitment module (UDM) 1 and UDM2. Here we report the crystal structures of the complex between UDM1 and Lys63-linked diUb (K63-Ub2) and that between the C-terminally truncated UDM2 (UDM2ΔC) and K63-Ub2. In both structures, UDM1 and UDM2ΔC fold as a single α-helix. Their simultaneous bindings to the distal and proximal Ub moieties provide specificity for Lys63-linked Ub chains. Structural and biochemical analyses of UDM1 elucidate an Ub-binding mechanism between UDM1 and polyubiquitylated targets. Mutations of Ub-interacting residues in UDM2 prevent the accumulation of RNF168 to DSB sites in U2OS cells, whereas those in UDM1 have little effect, suggesting that the interaction of UDM2 with ubiquitylated and polyubiquitylated targets mainly contributes to the RNF168 recruitment.
Disulfide isomerization reactions in titin immunoglobulin domains enable a mode of protein elasticity
Authors: Giganti David , Yan Kevin , Badilla Carmen L. , Fernandez Julio M. , Alegre-Cebollada Jorge 
Published: January 2018

AbstractThe response of titin to mechanical forces is a major determinant of the function of the heart. When placed under a pulling force, the unstructured regions of titin uncoil while its immunoglobulin (Ig) domains unfold and extend. Using single-molecule atomic force microscopy, we show that disulfide isomerization reactions within Ig domains enable a third mechanism of titin elasticity. Oxidation of Ig domains leads to non-canonical disulfide bonds that stiffen titin while enabling force-triggered isomerization reactions to more extended states of the domains. Using sequence and structural analyses, we show that 21% of titin’s I-band Ig domains contain a conserved cysteine triad that can engage in disulfide isomerization reactions. We propose that imbalance of the redox status of myocytes can have immediate consequences for the mechanical properties of the sarcomere via alterations of the oxidation state of titin domains.
Strong modulation of second-harmonic generation with very large contrast in semiconducting CdS via high-field domain
Authors: Ren Ming-Liang , Berger Jacob S. , Liu Wenjing , Liu Gerui , Agarwal Ritesh 
Published: January 2018

AbstractDynamic control of nonlinear signals is critical for a wide variety of optoelectronic applications, such as signal processing for optical computing. However, controlling nonlinear optical signals with large modulation strengths and near-perfect contrast remains a challenging problem due to intrinsic second-order nonlinear coefficients via bulk or surface contributions. Here, via electrical control, we turn on and tune second-order nonlinear coefficients in semiconducting CdS nanobelts from zero to up to 151 pm V−1, a value higher than other intrinsic nonlinear coefficients in CdS. We also observe ultrahigh ON/OFF ratio of >104 and modulation strengths ~200% V−1 of the nonlinear signal. The unusual nonlinear behavior, including super-quadratic voltage and power dependence, is ascribed to the high-field domain, which can be further controlled by near-infrared optical excitation and electrical gating. The ability to electrically control nonlinear optical signals in nanostructures can enable optoelectronic devices such as optical transistors and modulators for on-chip integrated photonics.
Picometer polar atomic displacements in strontium titanate determined by resonant X-ray diffraction
Authors: Richter Carsten , Zschornak Matthias , Novikov Dmitri , Mehner Erik , Nentwich Melanie , Hanzig Juliane , Gorfman Semën , Meyer Dirk C. 
Published: January 2018

AbstractPhysical properties of crystalline materials often manifest themselves as atomic displacements either away from symmetry positions or driven by external fields. Especially the origin of multiferroic or magnetoelectric effects may be hard to ascertain as the related displacements can reach the detection limit. Here we present a resonant X-ray crystal structure analysis technique that shows enhanced sensitivity to minute atomic displacements. It is applied to a recently found crystalline modification of strontium titanate that forms in single crystals under electric field due to oxygen vacancy migration. The phase has demonstrated unexpected properties, including piezoelectricity and pyroelectricity, which can only exist in non-centrosymmetric crystals. Apart from that, the atomic structure has remained elusive and could not be obtained by standard methods. Using resonant X-ray diffraction, we determine atomic displacements with sub-picometer precision and show that the modified structure of strontium titanate corresponds to that of well-known ferroelectrics such as lead titanate.
Calcium sulfate induced versus PMMA-induced membrane in a critical-sized femoral defect in a rat model
Authors: Ma Yun-fei , Jiang Nan , Zhang Xiang , Qin Cheng-he , Wang Lei , Hu Yan-jun , Lin Qing-rong , Yu Bin , Wang Bo-wei 
Published: January 2018

AbstractAimed to investigate the characteristics of CS-induced membrane in comparison with the PMMA-induced membrane. Cellular components, histological changes, growth factor expressions of IL-6, VEGF, BMP-2, and TGF-β1 in the two induced membranes were compared at 2, 4, 6 and 8 weeks, respectively. We also compared the histological changes at the bone defects between CS and PMMA groups. The structural characteristics of induced membrane were similar between CS and PMMA. Endochondral ossification took place in the CS-induced membrane at 8 week. Levels of VEGF, BMP-2 and TGF-β1 in CS-induced membrane were insignificantly higher than those in PMMA-induced membrane at different time points. The expression of IL-6 was significantly higher in PMMA-induced membranes at 2nd week. In addition, osteogenic and neovascular activities of induced membranes increased with time and peaked at 6 weeks. CS promoted endochondral ossification at the broken ends of the bone defect than PMMA did. CS-induced membrane has a better capacity of generating VEGF, BMP-2 and TGF-β1.osteogenic and neovascular activities achieve highest level at 6 week. CS may have the potential to replace PMMA as a novel spacer in Masquelet technique.
Discovery of microRNA-target modules of African rice (Oryza glaberrima) under salinity stress
Authors: Mondal Tapan Kumar , Panda Alok Kumar , Rawal Hukam C. , Sharma Tilak Raj 
Published: January 2018

AbstractOryza glaberrima is the second edible rice in the genus Oryza. It is grown in the African countries. miRNAs are regulatory molecules that are involved in every domains of gene expression including salinity stress response. Although several miRNAs have been reported from various species of Oryza, yet none of them are from this species. Salt treated (200 mM NaCl for 48 h) and control smallRNA libraries of RAM-100, a salt tolerant genotype, each with 2 replications generated 150 conserve and 348 novel miRNAs. We also used smallRNAseq data of NCBI of O. glaberrima to discover additional 246 known miRNAs. Totally, 29 known and 32 novel miRNAs were differentially regulated under salinity stress. Gene ontology and KEGG analysis indicated several targets were involved in vital biological pathways of salinity stress tolerance. Expression of selected miRNAs as indicated by Illumina data were found to be coherent with real time-PCR analysis. However, target gene expression was inversely correlated with their corresponding miRNAs. Finally based upon present results as well as existing knowledge of literature, we proposed the miRNA-target modules that were induced by salinity stress. Therefore, the present findings provide valuable information about miRNA-target networks in salinity adaption of O. glaberrima.
Polypharmacy through Phage Display: Selection of Glucagon and GLP-1 Receptor Co-agonists from a Phage-Displayed Peptide Library
Authors: Demartis Anna , Lahm Armin , Tomei Licia , Beghetto Elisa , Di Biasio Valentina , Orvieto Federica , Frattolillo Francesco , Carrington Paul E. , Mumick Sheena , Hawes Brian , Bianchi Elisabetta , Palani Anandan , Pessi Antonello 
Published: January 2018

AbstractA promising emerging area for the treatment of obesity and diabetes is combinatorial hormone therapy, where single-molecule peptides are rationally designed to integrate the complementary actions of multiple endogenous metabolically-related hormones. We describe here a proof-of-concept study on developing unimolecular polypharmacy agents through the use of selection methods based on phage-displayed peptide libraries (PDL). Co-agonists of the glucagon (GCG) and GLP-1 receptors were identified from a PDL sequentially selected on GCGR- and GLP1R-overexpressing cells. After two or three rounds of selection, 7.5% of randomly picked clones were GLP1R/GCGR co-agonists, and a further 1.53% were agonists of a single receptor. The phages were sequenced and 35 corresponding peptides were synthesized. 18 peptides were potent co-agonists, 8 of whom showed EC50 ≤ 30 pM on each receptor, comparable to the best rationally designed co-agonists reported in the literature. Based on literature examples, two sequences were engineered to stabilize against dipeptidyl peptidase IV cleavage and prolong the in vivo half-life: the engineered peptides were comparably potent to the parent peptides on both receptors, highlighting the potential use of phage-derived peptides as therapeutic agents. The strategy described here appears of general value for the discovery of optimized polypharmacology paradigms across several metabolically-related hormones.
High-performance flexible supercapacitors based on electrochemically tailored three-dimensional reduced graphene oxide networks
Authors: Purkait Taniya , Singh Guneet , Kumar Dinesh , Singh Mandeep , Dey Ramendra Sundar 
Published: January 2018

AbstractA simple approach for growing porous electrochemically reduced graphene oxide (pErGO) networks on copper wire, modified with galvanostatically deposited copper foam is demonstrated. The as-prepared pErGO networks on the copper wire are directly used to fabricate solid-state supercapacitor. The pErGO-based supercapacitor can deliver a specific capacitance (Csp) as high as 81±3 F g−1 at 0.5 A g−1 with polyvinyl alcohol/H3PO4 gel electrolyte. The Csp per unit length and area are calculated as 40.5 mF cm−1 and 283.5 mF cm−2, respectively. The shape of the voltammogram retained up to high scan rate of 100 V s−1. The pErGO-based supercapacitor device exhibits noticeably high charge-discharge cycling stability, with 94.5% Csp retained even after 5000 cycles at 5 A g−1. Nominal change in the specific capacitance, as well as the shape of the voltammogram, is observed at different bending angles of the device even after 5000 cycles. The highest energy density of 11.25 W h kg−1 and the highest power density of 5 kW kg−1 are also achieved with this device. The wire-based supercapacitor is scalable and highly flexible, which can be assembled with/without a flexible substrate in different geometries and bending angles for illustrating promising use in smart textile and wearable device.
miR-143-3p inhibits the proliferation, migration and invasion in osteosarcoma by targeting FOSL2
Authors: Sun Xiangran , Dai Guo , Yu Ling , Hu Qingzhu , Chen Jingteng , Guo Weichun 
Published: January 2018

AbstractOsteosarcoma (OS) is the most common type of primary malignant bone tumor and mainly occurs in children and adolescent. Because of its early migration and invasion, OS has a poor prognosis. It has been reported that mircoRNAs (miRNAs) play a crucial role in the occurrence and development of multiple tumors. In this study, we identified the aberrant-expression of miR-143-3p in osteosarcoma and examined the role of miR-143-3p in OS development. Further, we searched the miR-143-3p target gene and verified its accuracy by luciferase experiments. Finally, we explored the relationship between miR-143-3p and FOS-Like antigen 2 (FOSL2). Our data indicated that miR-143-3p expression was substantially lower in OS tissues and cell-line compared with normal tissues, and was lower in patients with poor prognosis. In addition miR-143-3p inhibited OS cell proliferation and metastasis while promoting apoptosis. We next showed that FOSL2 was directly targeted by miR-143-3p and could reverse the inhibition caused by miR-143-3p. Finally, we found FOSL2 expression in OS cells was significantly higher compared with normal cells and negatively correlated with miR-143-3p. Thus, miR-143-3p directly and negatively targets FOSL2 to affect OS characteristics. This provides a new target for the treatment of OS and deserves further study.