bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improvements in lipid suppression for 1H NMR‐based metabolomics: Applications to solution‐state and HR‐MAS NMR in natural and in vivo samples
Authors: Hassan Qusai , Dutta Majumdar Rudraksha , Wu Bing , Lane Daniel , Tabatabaei‐Anraki Maryam , Soong Ronald , Simpson Myrna J. , Simpson Andre J. 
Published: December 2018

AbstractProton nuclear magnetic resonance (NMR) spectra of intact biological samples often show strong contributions from lipids, which overlap with signals of interest from small metabolites. Pioneering work by Diserens et al. demonstrated that the relative differences in diffusivity and relaxation of lipids versus small metabolites could be exploited to suppress lipid signals, in high‐resolution magic angle spinning (HR‐MAS) NMR spectroscopy. In solution‐state NMR, suspended samples can exhibit very broad water signals, which are challenging to suppress. Here, improved water suppression is incorporated into the sequence, and the Carr‐Purcell‐Meiboom‐Gill sequence (CPMG) train is replaced with a low‐power adiabatic spinlock that reduces heating and spectral artefacts seen with longer CPMG filters. The result is a robust sequence that works well in both HR‐MAS as well as static solution‐state samples. Applications are also extended to include in vivo organisms. For solution‐state NMR, samples containing significant amount of fats such as milk and hemp hearts seeds are used to demonstrate the technique. For HR‐MAS, living earthworms (Eisenia fetida) and freshwater shrimp (Hyalella azteca) are used for in vivo applications. Lipid suppression techniques are essential for non‐invasive NMR‐based analysis of biological samples with a high‐lipid content and adds to the suite of experiments advantageous for in vivo environmental metabolomics.
Pegbelfermin (BMS‐986036), PEGylated FGF21, in Patients with Obesity and Type 2 Diabetes: Results from a Randomized Phase 2 Study
Authors: Charles Edgar D. , Neuschwander‐Tetri Brent A. , Pablo Frias Juan , Kundu Sudeep , Luo Yi , Tirucherai Giridhar S. , Christian Rose 
Published: December 2018

ObjectiveObesity and type 2 diabetes mellitus (T2DM) are risk factors for nonalcoholic fatty liver disease, including nonalcoholic steatohepatitis. This study assessed pegbelfermin (BMS‐986036), recombinant PEGylated human fibroblast growth factor 21 (FGF21), in patients with obesity and T2DM predisposed to fatty liver.MethodsIn this randomized, double‐blind, placebo‐controlled study, patients with T2DM and BMI of 30 to 50 kg/m2 received subcutaneous pegbelfermin (1, 5, or 20 mg daily or 20 mg weekly; n = 96) or placebo (n = 24) for 12 weeks. Primary end points were safety, tolerability, and change in HbA1c. Additional end points included insulin sensitivity, lipids, adiponectin, and disease progression biomarkers.ResultsThere were no significant effects of pegbelfermin versus placebo on HbA1c. Pegbelfermin 20 mg/d significantly improved high‐density lipoprotein cholesterol (P = 0.015) and triglycerides (P = 0.037). All pegbelfermin regimens significantly increased adiponectin levels; 20‐mg daily and weekly regimens decreased serum PRO‐C3. Most adverse events were mild; the most frequent adverse events were injection‐site bruising and diarrhea.ConclusionsTwelve‐week pegbelfermin treatment did not impact HbA1c concentrations, but QW and higher daily doses were associated with improved metabolic parameters and fibrosis biomarkers in patients with obesity and T2DM predisposed to fatty liver. These results support evaluation of pegbelfermin in patients with obesity‐related metabolic diseases (e.g., nonalcoholic steatohepatitis).
A design of shape memory networks of poly(ε‐caprolactone)s via POSS‐POSS interactions
Authors: Chang Pengfei , Xu Sen , Zhao Bingjie , Zheng Sixun 
Published: December 2018

In this contribution, we reported a design of shape memory networks of poly(ε‐caprolactone)s (PCLs) via POSS‐POSS interactions. First, a series of novel organic‐inorganic PCL stars with polyhedral oligomeric silsesquioxane (POSS) termini were synthesized via the combination of ring‐opening polymerization of ε‐caprolactone and the copper (I)‐catalyzed cycloaddition of alkynyl with azido groups. It was found that the organic‐inorganic PCL stars significantly displayed shape memory properties with about 100% of recovery. The morphological observation showed that in the organic‐inorganic PCL stars, the POSS cages at the ends of PCL chains were self‐organized into the spherical POSS microdomains with the size of 10 to 20 nm in diameter. The POSS microdomains behaved as the netpoints, resulting in the formation of physically crosslinked networks. The novel physically crosslinked networks endowed the organic‐inorganic nanocomposites with shape memory properties.
Outcomes following neonatal portal vein thrombosis: A descriptive, single‐center study and review of anticoagulant therapy
Authors: Bhatt Mihir D. , Patel Vishal , Butt Michelle L. , Chan Anthony K.C. , Paes Bosco ,   the Thrombosis and Hemostasis in Newborns (THiN) Group
Published: December 2018

AbstractBackgroundNeonatal portal vein thrombosis (PVT) is uncommon with potentially serious complications that may manifest in infancy and childhood.ObjectiveThe primary aim of our study was to describe the short‐term and long‐term outcomes of neonatal PVT.MethodsA retrospective chart review was conducted from 2008 to 2016 of neonates diagnosed with PVT. A systematic review was also performed from 2000 to 2018 to evaluate anticoagulant therapy (ACT) in neonatal PVT.ResultsForty‐four premature and 30 term infants (mean gestational age 30.7 vs 39.1 weeks, respectively) had PVT. Sixty‐eight involved the left portal vein, one involved only the main portal vein, and 5 involved ≥1 vein. PVT was catheter associated in 46 (62%); none of the 7 neonates tested had thrombophilia. Of 74 neonates, 19 (26%) received ACT and 55 (74%) were untreated. The mean follow‐up duration was 16.6 months (SD = 17.62; range, 0–89.6); 59.5% were followed for ≥6 months. On last ultrasound examination, thrombus resolution was documented in treated (ACT; n = 19) and nontreated (n = 55) neonates: 12 (63%) versus 32 (58%) with complete resolution, 1 (5%) versus 6 (11%) partial, 0 versus 1 (2%) extension, and 6 (32%) versus 16 (29%) had nonprogressive lesions, respectively. Seventy‐one (96%) had no complications. Seventy‐one articles met inclusion criteria for the systematic review and 19 were retained for analysis after assessment.ConclusionsPVT resolution rate was similar to previous reports. Although a low complication rate was detected, longer follow‐up is necessary to determine the need for early treatment and the precise incidence of outcomes such as portal hypertension.
Co‐design of an evidence‐based health education diabetes foot app to prevent serious foot complications: a feasibility study
Authors: Ogrin Rajna , Viswanathan Rekha , Aylen Tracy , Wallace Fiona , Scott Janine , Kumar Dinesh 
Published: December 2018

AbstractDiabetes is the most common cause of non‐traumatic amputations worldwide, and education is key to prevention. Mobile phones and applications (apps) are increasingly being used. This study co‐designed and assessed whether a foot health education app would be feasible and acceptable to support people with diabetes (PWD) to prevent serious foot complications.A diabetes foot app was co‐designed with PWD, experts, researchers and biomedical engineers following co‐design principles. The app was piloted in a convenience sample of adults with diabetes from one community health service in metropolitan Melbourne for 12 weeks. Baseline quantitative data were collected on foot health, knowledge, self‐care behaviours and attitudes. Qualitative data were collected post intervention to capture experiences of using the app, using interviews and focus groups.The co‐designed app included information on amputation risk and self‐care practices to prevent serious foot complications. The content used images and simple wording, focusing on early help‐seeking behaviour. Forty participants with a mean age of 66.9±17.1 years were included in the pilot. Seven participants withdrew due to personal and health‐related issues.Uptake of the app was low, with 18 participants using the app for any period of time. Qualitative interviews or focus groups were undertaken with 31 participants. Overall, the information was perceived as highly useful for newly‐diagnosed PWD and worth pursuing. Future work is needed to identify which PWD would most benefit, and incorporate aspects relating to increased opportunity and motivation for behaviour change and a centralised data management system to provide updates. Copyright © 2018 John Wiley & Sons.
Targeted Feature Extraction in MALDI Mass Spectrometry Imaging to Discriminate Proteomic Profiles of Breast and Ovarian Cancer
Authors: Cordero Hernandez Yovany , Boskamp Tobias , Casadonte Rita , Hauberg‐Lotte Lena , Oetjen Janina , Lachmund Delf , Peter Annette , Trede Dennis , Kriegsmann Katharina , Kriegsmann Mark , Kriegsmann Jörg , Maass Peter 
Published: December 2018

PurposeTo develop a mass spectrometry imaging (MSI) based workflow for extracting m/z values related to putative protein biomarkers and using these for reliable tumor classification.Experimental designGiven a list of putative breast and ovarian cancer biomarker proteins, a set of related m/z values are extracted from heterogeneous MSI datasets derived from formalin‐fixed paraffin‐embedded tissue material. Based on these features, a linear discriminant analysis classification model is trained to discriminate the two tumor types.ResultsIt is shown that the discriminative power of classification models based on the extracted features is increased compared to the automatic training approach, especially when classifiers are applied to spectral data acquired under different conditions (instrument, preparation, laboratory).Conclusions and clinical relevanceRobust classification models not confounded by technical variation between MSI measurements are obtained. This supports the assumption that the classification of the respective tumor types is based on biological rather than technical differences, and that the selected features are related to the proteomic profiles of the tumor types under consideration.
Implementation of Clinical Proteomics: A Step Closer to Personalized Medicine?
Authors: Vlahou Antonia 
Published: December 2018

AbstractThe success of clinical proteomics, per definition, is ultimately defined by the clinical implementation of proteomics findings. Extensive research activity in the field, targeting especially biomarker discovery, has been conducted in the past decades, with several studies suggesting a benefit from proteome‐based application in patient management. This viewpoint article discusses the current status in clinical proteomics with respect to implementation (as evidenced by the use of protein findings in drug labeling and patient stratification), and proposes specific action points for accelerating the biomarker validation process, placing special emphasis on the importance of data and resource sharing.
Proteomic Landscape of Cholangiocarcinomas Reveals Three Different Subgroups According to Their Localization and the Aspect of Non‐Tumor Liver
Authors: Le Faouder Julie , Gigante Elia , Léger Thibaut , Albuquerque Miguel , Beaufrère Aurélie , Soubrane Olivier , Dokmak Safi , Camadro Jean‐Michel , Cros Jérôme , Paradis Valérie 
Published: December 2018

PurposeCholangiocarcinomas (CCs) define a heterogeneous entity based upon their anatomic localization (intra versus extrahepatic) and, for the intrahepatic CCs, the aspect of background liver (normal versus cirrhosis). The aim of the study was to characterize the molecular heterogeneity of CCs by a global proteomic approach.Experimental designThirty‐three tumor samples from 17 intrahepatic CCs (iCC) (9 developed on normal (iCCN) and 8 developed in cirrhotic liver (iCCC)); 5 hilar CCs (CCH); 5 pancreatic CCs (CCP) and 6 hepatocellular carcinomas (HCC), were submitted to label‐free quantitative proteomic analysis. Differential proteins were analyzed by immunohistochemistry in a validation set of 30 CCs.ResultsUnsupervised analysis revealed two main clusters: cluster 1 contained most of the iCCC while cluster 2 was divided in 2 subgroups, one containing most of the iCCN and the other regrouping CCH and CCP. Compared to iCCN, iCCC displayed upregulation of molecules involved in cell adhesion, motility and angiogenesis. Epithelial markers associated with secretory pathway and fibroblast markers were overexpressed in CCH compared to iCCNConclusion and clinical relevanceThis study demonstrated that iCCC is a specific entity, suggesting a major impact of the background liver on tumor biology, and confirmed that extrahepatic CCs define a homogeneous subgroup.
High‐resolution crystal structure of peptidyl‐tRNA hydrolase from Thermus thermophilus
Authors: Matsumoto Ami , Uehara Yuji , Shimizu Yoshihiro , Ueda Takuya , Uchiumi Toshio , Ito Kosuke 
Published: December 2018

AbstractPeptidyl‐tRNA hydrolase (Pth) cleaves the ester bond between the peptide and the tRNA of peptidyl‐tRNA molecules, which are the products of defective translation, to recycle the tRNA for further rounds of protein synthesis. Pth is ubiquitous in nature, and its activity is essential for bacterial viability. Here, we have determined the crystal structure of Pth from Thermus thermophilus (TtPth) at 1.00 Å resolution. This is the first structure of a Pth from a thermophilic bacterium and the highest resolution Pth structure reported so far. The present atomic resolution data enabled the calculation of anisotropic displacement parameters for all atoms, which revealed the directionality of the fluctuations of key regions for the substrate recognition. Comparisons between TtPth and mesophilic bacterial Pths revealed that their structures are similar overall. However, the structures of the N‐ and C‐terminal, loop‐helix α4, and helix α6 regions are different. In addition, the helix α1 to strand β4 region of TtPth is remarkably different from those of the mesophilic bacterial Pths, because this region is 9 or 10 amino acid residues shorter than those of the mesophilic bacterial Pths. This shortening seems to contribute to the thermostability of TtPth. To further understand the determinants for the thermostability of TtPth, we compared various structural factors of TtPth with those of mesophilic bacterial Pths. The data suggest that the decreases in accessible surface area and thermolabile amino acid residues, and the increases in ion pairs, hydrogen bonds, and proline residues cooperatively contribute to the thermostability of TtPth.
Rapid and accurate structure‐based therapeutic peptide design using GPU accelerated thermodynamic integration
Authors: Garton Michael , Corbi‐Verge Carles , Hu Yuan , Nim Satra , Tarasova Nadya , Sherborne Brad , Kim Philip M. 
Published: December 2018

AbstractPeptide‐based therapeutics are an alternative to small molecule drugs as they offer superior specificity, lower toxicity, and easy synthesis. Here we present an approach that leverages the dramatic performance increase afforded by the recent arrival of GPU accelerated thermodynamic integration (TI). GPU TI facilitates very fast, highly accurate binding affinity optimization of peptides against therapeutic targets. We benchmarked TI predictions using published peptide binding optimization studies. Prediction of mutations involving charged side‐chains was found to be less accurate than for non‐charged, and use of a more complex 3‐step TI protocol was found to boost accuracy in these cases. Using the 3‐step protocol for non‐charged side‐chains either had no effect or was detrimental. We use the benchmarked pipeline to optimize a peptide binding to our recently discovered cancer target: EME1. TI calculations predict beneficial mutations using both canonical and non‐canonical amino acids. We validate these predictions using fluorescence polarization and confirm that binding affinity is increased. We further demonstrate that this increase translates to a significant reduction in pancreatic cancer cell viability.
Synthesis, insecticidal activity, and phytotoxicity of novel chiral amides
Authors: Aguiar Alex R , Alvarenga Elson S , Silva Eliete MP , Farias Elizeu S , Picanço Marcelo C 
Published: December 2018

AbstractBACKGROUNDThe lesser grain borer, Rhyzopertha dominica (F.) (Coleoptera: Bostrychidae), is an important pest of stored grains worldwide. Chemical control is the main method used to manage this pest, but the continuous use of insecticides can lead to the selection of resistant R. dominica strains. Thus, there is a constant demand for the development of new insecticide molecules. This study describes the synthesis of 14 chiral amides and evaluation of their insecticidal activity against R. dominica. Their phytotoxicity to wheat (Triticum sativum) seeds is also evaluated.RESULTSIn the screening assay, compounds 8i and 8j caused 100% and 87% mortality of R. dominica. These values did not differ from the mortality caused by Bifenthrin® (75%). Amide 8i presented similar toxicity (LD50 = 27.98 µmol g−1, CI95 = 25.14–30.71) and speed of action (LT50 = 22 h, CI95 = 19.34–24.66) to amide 8j (LD50 = 29.37 µmol g−1, CI95 = 27.43–31.09, and LT50 = 19 h, CI95 = 17.05–20.95) against the pest. Both amides inhibited less than 44% of wheat growth.CONCLUSIONAmong the tested amides, only 8i and 8j were effective in R. dominica control and presented no considerable phytotoxicity towards wheat seeds. Therefore, these amides are promising as insecticides for the management of R. dominica. © 2018 Society of Chemical Industry
Enhanced Zintl anions by carbon doping in Al‐Na clusters and new magic structure Al6Na4C
Authors: Tang Jianling , Zhang Cairong , Du Ning , Zhao Yanyan , Chen Hongshan 
Published: December 2018

AbstractThis article investigated the low‐energy structures of Al6Na
mC (m = 2, 4, 6, 8) clusters and their electronic structures by using genetic algorithm combined with density functional theory and configuration interaction methods. The computations show that the C atoms prefer sitting at the center, whereas the Na atoms tend to locate at the outside of the clusters. The valence molecular orbitals (MOs) agree well with the prediction of the jellium model. The stronger attraction of the central carbon to the valence electrons will depress the potential energies locally, which makes the 2S level go obviously lower and the 2P and 1D orbitals form a sub‐band. The 26 valence electrons in Al6Na4C form closed 1S21P62S21D102P6 shells and correspond to a new magic structure. The MOs and electron localization function show that the sodium cores are exposed at the outside of the valence electrons and form naked cations. The contraction of the valence electrons because of the carbon doping enhances the charges on the Al6C moieties, and the Na+ cores on the peripheries are ionically bonded to the Zintl anions (Al6C)q−. The Al6Na4C has a tetrahedral structure with symmetry Td, and it may be used as building blocks to synthesize Zintl solid.
Streamlining non‐governmental organizations' programs towards achieving the sustainable development goals: A conceptual framework
Authors: Hassan Mohamad Muhyiddin , Lee Khai Ern , Mokhtar Mazlin 
Published: December 2018

AbstractAfter the launching of sustainable development goals (SDGs), nongovernmental organizations (NGOs) are identified as prominent players in localizing the SDGs. This has drawn attention of the research communities to shift from single‐sector approach to cross‐sectors approach in achieving the SDGs. However, the different capacity of NGOs is defined by the gaps of institutional factors and different approaches contributing to uncertain impacts that cannot be measured persistently. This limitation has caused many NGOs to choose in maintaining single‐sector approach that has been practiced in the millennium development goals previously. Subsequently, this may result to the lack of SDGs output exchange from the NGOs. Therefore, this paper proposes a conceptual framework to streamline NGOs' programs towards achieving the SDGs in two mechanisms, namely, cross‐sectors partnerships and broadening social value. Cross‐sectors partnerships are developed crossing around the institutional sectors of society as one central partnering process to organize and respond to common issues and concerns in SDGs. Broadening social value is one form of NGO's mechanisms to raise a social interest crossing into many sectors in the role of shifting single‐sector approach to cross‐sectors approach. This conceptual framework provides a basis for NGOs to plan their programs based on their capability and capacity in achieving the SDGs' target.
Spatio‐temporal analysis of economic, social, and environmental issues in the framework of sustainable development in worldwide countries
Authors: Rodríguez‐Rosa Miguel , Gallego‐Álvarez Isabel , Galindo‐Villardón Mª. Purificación 
Published: December 2018

AbstractSustainability indicators make it possible to clearly and effectively show the general public the position of different countries with respect to sustainability, to assist governments in decision‐making concerning social, environmental, and economic strategies, and to approve plans and tactics. Sustainability is now an important global issue. So many institutions are facing the challenge of building new mathematical models and developing algorithms that can confirm that we are making progress towards a more sustainable society. Given the current dearth of such methods, we thought it would be valuable to develop a new system for use in the study of sustainability, a system that will help to explain the effects of each country, describing sustainability through the use of several indicators. The Sustainable Society Index is used in the present research for the period 2006–2012. The co‐Tucker3 method is used to describe interactions between the rows, columns, and repetitions of two sequences of matrices, by reducing their dimensionality, that is, the number of elements in them. Plots are used to visualise differences or similarities in the data, for example, groups of countries that score differently on some indicators during some years, relationships between indicators, and temporal trends. Thus, our methodology makes it possible to deduce relationships among countries and temporal trends based on sustainability indicator data.
Synthesis, Single‐Crystal X‐Ray, Hirshfeld and Antimicrobial Evaluation of some New Imidazopyridine Nucleus Incorporated with Oxadiazole Scaffold
Authors: Kuthyala Sharanya , Shankar Madan K , Nagaraja Gundibasappa K 
Published: December 2018

AbstractTo avert the menace of pathogens in medical parlance, emerging attractive strategy is combining two different active fragments in a single molecule for scientific solutions. Trisubstituted imidazo[1,2‐a]pyridine‐carboxylate was engrossed as a hybrid with oxadiazole. The three dimensional and crystal structures of compounds 3‐[5‐(2‐chlorophenyl)‐1,3,4‐oxadiazol‐2‐yl]‐2,8‐dimethylimidazo[1,2‐a]pyridine (4 c) and 3‐(5‐benzyl‐1,3,4‐oxadiazol‐2‐yl)‐2,8‐dimethylimidazo[1,2‐a]pyridine (4 e) were determined using single crystal X‐ray diffraction studies and their crystal packing was analyzed using Hirshfeld surface computational analysis. The molecular conformation of 4 c (planar) and 4 e (twisted) and crystal packing is different and this may be due to substitution effect. In addition, both compounds have common intermolecular interactions of the type C–H…π and intercontacts H…H contributes more to the Hishfeld surfaces. Screening for microbial activity acknowledged, 2,8‐dimethyl‐3‐[5‐(3‐nitrophenyl)‐1,3,4‐oxadiazol‐2‐yl]imidazo[1,2‐a]pyridine (4 f) and 6‐chloro‐2‐methyl‐3‐[5‐(4‐methylphenyl)‐1,3,4‐oxadiazol‐2‐yl]imidazo[1,2‐a]pyridine (4 g) as most effective against Staphyllococus aureus, over all other derivatives. Meanwhile, 4 f also showed pronounced antifungal activity against Candida albicans. Further 4 f was endorsed by time kill assay as bactericidal in its action.