bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polypeptide templating for designer hierarchical materials
Authors: Sun Hui , Marelli Benedetto 
Published: January 2020

AbstractDespite advances in directing the assembly of biomacromolecules into well-defined nanostructures, leveraging pathway complexity of molecular disorder to order transition while bridging materials fabrication from nano- to macroscale remains a challenge. Here, we present templated crystallization of structural proteins to nanofabricate hierarchically structured materials up to centimeter scale, using silk fibroin as an example. The process involves the use of ordered peptide supramolecular assemblies as templates to direct the folding and assembly of silk fibroin into nanofibrillar structures. Silk polymorphs can be engineered by varying the peptide seeds used. Modulation of the relative concentration between silk fibroin and peptide seeds, silk fibroin molecular weight and pH allows control over nanofibrils morphologies and mechanical properties. Finally, facile integration of the bottom-up templated crystallization with emerging top-down techniques enables the generation of macroscopic nanostructured materials with potential applications in information storage/encryption, surface functionalization, and printable three-dimensional constructs of customized architecture and controlled anisotropy.
Heavy metals contaminating the environment of a progressive supranuclear palsy cluster induce tau accumulation and cell death in cultured neurons
Authors: Alquezar Carolina , Felix Jessica B. , McCandlish Elizabeth , Buckley Brian T. , Caparros-Lefebvre Dominique , Karch Celeste M. , Golbe Lawrence I. , Kao Aimee W. 
Published: January 2020

AbstractProgressive supranuclear palsy (PSP) is a neurodegenerative disorder characterized by the presence of intracellular aggregates of tau protein and neuronal loss leading to cognitive and motor impairment. Occurrence is mostly sporadic, but rare family clusters have been described. Although the etiopathology of PSP is unknown, mutations in the MAPT/tau gene and exposure to environmental toxins can increase the risk of PSP. Here, we used cell models to investigate the potential neurotoxic effects of heavy metals enriched in a highly industrialized region in France with a cluster of sporadic PSP cases. We found that iPSC-derived iNeurons from a MAPT mutation carrier tend to be more sensitive to cell death induced by chromium (Cr) and nickel (Ni) exposure than an isogenic control line. We hypothesize that genetic variations may predispose to neurodegeneration induced by those heavy metals. Furthermore, using an SH-SY5Y neuroblastoma cell line, we showed that both heavy metals induce cell death by an apoptotic mechanism. Interestingly, Cr and Ni treatments increased total and phosphorylated tau levels in both cell types, implicating Cr and Ni exposure in tau pathology. Overall, this study suggests that chromium and nickel could contribute to the pathophysiology of tauopathies such as PSP by promoting tau accumulation and neuronal cell death.
Facile and efficient 3-chlorophenol sensor development based on photolumenescent core-shell CdSe/ZnS quantum dots
Authors: Rahman Mohammed M. , Karim Mohammad Rezaul , Alam M. M. , Zaman M. Badruz , Alharthi Nabeel , Alharbi Hamad , Asiri Abdullah M. 
Published: January 2020

AbstractQuantum dots (QDs) are semiconducting inorganic nanoparticles, tiny molecules of 2–10 nm sizes to strength the quantum confinements of electrons. The QDs are good enough to emit light onto electrons for exciting and returning to the ground state. Here, CdSe/ZnS core/shell QDs have been prepared and applied for electrochemical sensor development in this approach. Flat glassy carbon electrode (GCE) was coated with CdSe/ZnS QDs as very thin uniform layer to result of the selective and efficient sensor of 3-CP (3-chlorophenol). The significant analytical parameters were calculated from the calibration plot such as sensitivity (3.6392 µA µM−1 cm−2) and detection limit (26.09 ± 1.30 pM) with CdSe/ZnS/GCE sensor probe by electrochemical approach. The calibration curve was fitted with the regression co-efficient r2 = 0.9906 in the range of 0.1 nM ∼ 0.1 mM concentration, which denoted as linear dynamic range (LDR). Besides these, it was performed the reproducibility in short response time and successfully validated the fabricated sensor for 3-CP in the real environmental and extracted samples. It is introduced as a noble route to detect the environmental phenolic contaminants using CdSe/ZnS QDs modified sensor by electrochemical method for the safety of healthcare and environmental fields at broad scales.
Establishment of novel long-term cultures from EpCAM positive and negative circulating tumour cells from patients with metastatic gastroesophageal cancer
Authors: Brungs Daniel , Minaei Elahe , Piper Ann-Katrin , Perry Jay , Splitt Ashleigh , Carolan Martin , Ryan Shantay , Wu Xiao Juan , Corde Stéphanie , Tehei Moeava , Aghmesheh Morteza , Vine Kara L. , Becker Therese M. , Ranson Marie 
Published: January 2020

AbstractCirculating tumour cell (CTC) enumeration and profiling has been established as a valuable clinical tool in many solid malignancies. A key challenge in CTC research is the limited number of cells available for study. Ex vivo CTC culture permits expansion of these rare cell populations for detailed characterisation, functional assays including drug sensitivity testing, and investigation of the pathobiology of metastases. We report for the first time the establishment and characterisation of two continuous CTC lines from patients with gastroesophageal cancer. The two cell lines (designated UWG01CTC and UWG02CTC) demonstrated rapid tumorigenic growth in immunodeficient mice and exhibit distinct genotypic and phenotypic profiles which are consistent with the tumours of origin. UWG02CTC exhibits an EpCAM+, cytokeratin+, CD44+ phenotype, while UWG01CTC, which was derived from a patient with metastatic neuroendocrine cancer, displays an EpCAM−, weak cytokeratin phenotype, with strong expression of neuroendocrine markers. Further, the two cell lines show distinct differences in drug and radiation sensitivity which match differential cancer-associated gene expression pathways. This is strong evidence implicating EpCAM negative CTCs in metastasis. These novel, well characterised, long-term CTC cell lines from gastroesophageal cancer will facilitate ongoing research into metastasis and the discovery of therapeutic targets.
In situ Rb-Sr dating of slickenfibres in deep crystalline basement faults
Authors: Tillberg Mikael , Drake Henrik , Zack Thomas , Kooijman Ellen , Whitehouse Martin J. , Åström Mats E. 
Published: January 2020

AbstractEstablishing temporal constraints of faulting is of importance for tectonic and seismicity reconstructions and predictions. Conventional fault dating techniques commonly use bulk samples of syn-kinematic illite and other K-bearing minerals in fault gouges, which results in mixed ages of repeatedly reactivated faults as well as grain-size dependent age variations. Here we present a new approach to resolve fault reactivation histories by applying high-spatial resolution Rb-Sr dating to fine-grained mineral slickenfibres in faults occurring in Paleoproterozoic crystalline rocks. Slickenfibre illite and/or K-feldspar together with co-genetic calcite and/or albite were targeted with 50 µm laser ablation triple quadrupole inductively coupled plasma mass spectrometry analyses (LA-ICP-MS/MS). The ages obtained disclose slickenfibre growth at several occasions spanning over 1 billion years, from at least 1527 Ma to 349 ± 9 Ma. The timing of these growth phases and the associated structural orientation information of the kinematic indicators on the fracture surfaces are linked to far-field tectonic events, including the Caledonian orogeny. Our approach links faulting to individual regional deformation events by minimizing age mixing through micro-scale analysis of individual grains and narrow crystal zones in common fault mineral assemblages.
Novel Chimeric Multiepitope Vaccine for Streptococcosis Disease in Nile Tilapia (Oreochromis niloticus Linn.)
Authors: Pumchan Ansaya , Krobthong Sucheewin , Roytrakul Sittiruk , Sawatdichaikul Orathai , Kondo Hidehiro , Hirono Ikuo , Areechon Nontawith , Unajak Sasimanas 
Published: January 2020

AbstractStreptococcus agalactiae is a causative agent of streptococcosis disease in various fish species, including Nile tilapia (Oreochromis niloticus Linn.). Vaccination is an effective disease prevention and control method, but limitations remain for protecting against catastrophic mortality of fish infected with different strains of streptococci. Immunoproteomics analysis of S. agalactiae was used to identify antigenic proteins and construct a chimeric multiepitope vaccine. Epitopes from five antigenic proteins were shuffled in five helices of a flavodoxin backbone, and in silico analysis predicted a suitable RNA and protein structure for protein expression. 45F2 and 42E2 were identified as the best candidates for a chimeric multiepitope vaccine. Recombinant plasmids were constructed to produce a recombinant protein vaccine and DNA vaccine system. Overexpressed proteins were determined to be 30 kDa and 25 kDa in the E. coli and TK1 systems, respectively. The efficacy of the chimeric multiepitope construct as a recombinant protein vaccine and DNA vaccine was evaluated in Nile tilapia, followed by S. agalactiae challenge at 1 × 107 CFU/mL. Relative percentage survival (RPS) and cumulative mortality were recorded at approximately 57–76% and 17–30%, respectively. These chimeric multiepitope vaccines should be applied in streptococcosis disease control and developed into a multivalent vaccine to control multiple diseases.
Dose-dependent effect of cannabinoid WIN-55,212-2 on myelin repair following a demyelinating insult
Authors: Tomas-Roig J. , Agbemenyah H. Y. , Celarain N. , Quintana E. , Ramió-Torrentà Ll. , Havemann-Reinecke U. 
Published: January 2020

AbstractDysfunctions in the endocannabinoid system have been associated with experimental animal models and multiple sclerosis patients. Interestingly, the endocannabinoid system has been reported to confer neuroprotection against demyelination. The present study aims to assess the effects of the cannabinoid agonist WIN-55,212-2 in cuprizone fed animals on myelin repair capacity. Animals exposed to cuprizone were simultaneously treated withWIN-55,212-2, behaviorally tested and finally the corpus callosum was exhaustively studied by Western blotting, qRT-PCR and a myelin staining procedure. We report that the long-term administration of WIN-55,212-2 reduced the global amount of CB1 protein. Histological analysis revealed clear demyelination after being fed cuprizone for three weeks. However, cuprizone-fed mice subjected to 0.5 mg/Kg of WIN-55,212-2 displayed no differences when compared to controls during demyelination, although there was a robust increase in the myelinated axons during the remyelination phase. These animals displayed better performance on contextual fear conditioning which was in turn non-attributable to an antinociceptive effect. In contrast, a 1 mg/Kg dosage caused a remarkable demyelination accompanied by limited potential for myelin repair. Upon drug administration while mice ongoing demyeliniation, the expression of Aif1 (microglia) and Gfap (astrocytes) followed a dose-dependent manner whereas the expression of both markers was apparently attenuated during remyelination. Treatment with vehicle or 0.5 mg/Kg of the drug during demyelination increased the expression of Pdgfra (oligodendrocyte precursor cells) but this did not occur when 1 mg/Kg was administered. In conclusion, the drug at 0.5 mg/Kg did not alter myelin architecture while 1 mg/Kg had a deleterious effect in this model.
NIHSS is not enough for cognitive screening in acute stroke: A cross-sectional, retrospective study
Authors: Abzhandadze Tamar , Reinholdsson Malin , Stibrant Sunnerhagen Katharina 
Published: January 2020

AbstractThe aim of this study was to investigate whether the cognitive subscale of the National Institute of Health Stroke Scale (NIHSS), the Cog-4, can detect cognitive deficits in acute stroke. This was a cross-sectional, retrospective study. The study sample consisted of people with stroke enrolled in an acute stroke unit. The index test Cog-4 was calculated based on admission NIHSS score. The reference standard instrument, the Montreal Cognitive Assessment (MoCA), was performed within 36–48 h of admission. Non-parametric statistics were used for data analyses. The study included 531 participants with a mean age of 69 years. The Cog-4 failed to identify cognitive deficits in 65%, 58%, and 53% of patients when the MoCA thresholds for impaired cognition were set at ≤25 p, ≤23 p, and ≤19 p, respectively, were chosen for impaired cognition. The agreement between the Cog-4 and the MoCA was poor; Cohen’s kappa was from −0.210 to −0.109, depending on the MoCA cut-offs. The sensitivity of the Cog-4 was 35%, 42% and 48% for the MoCA thresholds for impaired cognition ≤25, ≤23 and ≤19 points, respectively. The Cog-4 has a limited ability to identify cognitive deficits in acute stroke. More structured and comprehensive tests should be employed as diagnostic tools.
Biomechanical comparison of the use of different surgical suture techniques for continuous loop tendon grafts preparation
Authors: Zhang Chen , Götschi Tobias , Li Xiang , Snedeker Jess G. , Fucentese Sandro F. 
Published: January 2020

AbstractWe introduce a new approach for a continuous loop tendon-graft preparation, benchmarking it against established graft preparation techniques widely used in conjunction with non-adjustable interference screw fixation. A four-strand bovine tendon graft was prepared using the following graft preparation techniques: standard graft using the baseball stitch technique (M-tech group); continuous loop graft using the GraftLinkTM technique (Arthrex-tech group); continuous loop graft using the Kessler anastomosis technique (Kessler-tech group); and continuous loop graft using a Double-Z anastomosis technique (Double Z-tech group). Each group of eight specimens underwent cyclic loading followed by a load-to-failure test. The M–technique yielded a smaller graft diameter (8.4 ± 0.5 mm) compared to the statistically equivalent diameters of the three continuous loop techniques (8.9 ± 0.6 mm of Arthrex-tech group, 9.1 ± 0.4 mm of Kessler-tech group and 9.2 ± 0.6 mm of Double Z-Tech group). The continuous loop grafts formed by the Double Z-Technique showed outstanding performance among the tested techniques in terms of ultimate failure load (982 ± 121 N) and cyclic elongation (3.7 ± 1.0 mm). There was no significant difference between the four groups in cyclic stiffness. Of the assessed techniques, the Arthrex technique resulted in the lowest ultimate elongation (2.0 ± 0.7 mm), followed by the Double Z-tech (4.5 ± 1.8 mm), the M-tech (5.2 ± 3.9 mm), and the Kessler-tech (5.3 ± 2.4 mm). The Arthrex-tech group (5.98 ± 0.38 min) displayed the shortest graft preparation time, followed by the M-Tech (7.94 ± 0.58 min), Kessler-tech (9.03 ± 0.39 min) and Double Z-Tech (13.29 ± 1.14 min). Double Z-Tech can improve the construct of continuous loop tendon graft with regard to mechanical performance.
High H2O Content in Pyroxenes of Residual Mantle Peridotites at a Mid Atlantic Ridge Segment
Authors: Li Pei , Xia Qun-Ke , Dallai Luigi , Bonatti Enrico , Brunelli Daniele , Cipriani Anna , Ligi Marco 
Published: January 2020

AbstractGlobal correlations of mid-ocean-ridges basalt chemistry, axial depth and crustal thickness have been ascribed to mantle temperature variations affecting degree of melting. However, mantle H2O content and elemental composition may also play a role. How H2O is distributed in the oceanic upper mantle remains poorly constrained. We tackled this problem by determining the H2O content of orthopyroxenes (opx) and clinopyroxenes (cpx) of peridotites from a continuous lithospheric section created during 26 Ma at a 11°N Mid-Atlantic Ridge segment, and exposed along the Vema Transform. The H2O content of opx ranges from 119 ppm to 383 ppm; that of cpx from 407 ppm to 1072 ppm. We found anomalous H2O-enriched peridotites with their H2O content not correlating inversely with their degree of melting, although H2O is assumed to be incompatible during melting. Inverse correlation of H2O with Ce, another highly incompatible component, suggests post-melting H2O enrichment. We attribute a major role to post-melting temperature-dependent diffusion of hydrogen occurring above the melting region, where water-rich melt flows faster than residual peridotites through dunitic conduits cross-cutting the uprising mantle. Accordingly, estimates of the H2O content of the MORB mantle source based on H2O in abyssal peridotites can be affected by strong uncertainties.
Identification of genetic polymorphisms modulating nausea and vomiting in two series of opioid-treated cancer patients
Authors: Colombo Francesca , Pintarelli Giulia , Galvan Antonella , Noci Sara , Corli Oscar , Skorpen Frank , Klepstad Pål , Kaasa Stein , Pigni Alessandra , Brunelli Cinzia , Roberto Anna , Piazza Rocco , Pirola Alessandra , Gambacorti-Passerini Carlo , Caraceni Augusto Tommaso 
Published: January 2020

AbstractNausea and vomiting are often associated with opioid analgesia in cancer patients; however, only a subset of patients develop such side effects. Here, we tested the hypothesis that the occurrence of nausea and vomiting is modulated by the genetic background of the patients. Whole exome sequencing of DNA pools from patients with either low (n = 937) or high (n = 557) nausea and vomiting intensity, recruited in the European Pharmacogenetic Opioid Study, revealed a preliminary association of 53 polymorphisms. PCR-based genotyping of 45 of these polymorphisms in the individual patients of the same series confirmed the association for six SNPs in AIM1L, CLCC1, MUC16, PDE3A, POM121L2, and ZNF165 genes. Genotyping of the same 45 polymorphisms in 264 patients of the Italian CERP study, also treated with opioids for cancer pain, instead confirmed the association for two SNPs in ZNF568 and PDE3A genes. Only one SNP, rs12305038 in PDE3A, was confirmed in both series, although with opposite effects of the minor allele on the investigated phenotype. Overall, our findings suggest that genetic factors are indeed associated with nausea and vomiting in opioid-treated cancer patients, but the role of individual polymorphisms may be weak.
No Evidence of Off-label Use of Olodaterol and Indacaterol in Denmark, France, and the Netherlands: A Drug Utilization Study
Authors: Rebordosa Cristina , Houben Eline , Laugesen Kristina , Bothner Ulrich , Montonen Jukka , Aguado Jaume , Overbeek Jetty A. , Ehrenstein Vera , Asmar Joelle , Wallace Laura , Gilsenan Alicia W. 
Published: January 2020

AbstractTo characterize the use of olodaterol and indacaterol in clinical practice and to quantify the off-label use in asthma. Drug utilization study of new users of olodaterol or indacaterol between 2014 and 2017 in the PHARMO Database Network in the Netherlands, the Danish population registers, and the IMS Real-World Evidence Longitudinal Patient Database panels in France. On-label use was defined as use among adults with a recorded diagnosis of COPD. Off-label use was defined as use among adults with a recorded diagnosis of asthma without a recorded diagnosis of COPD or as use among patients aged ≤18 years. Potential off-label use was defined as no recorded diagnosis of either COPD or asthma. The study included 4,158 new users of olodaterol and 9,966 new users of indacaterol. Prevalence of off-label use ranged from 3.5% for both drugs to 12.4% for olodaterol and 11.9% for indacaterol. Prevalence of on-label use ranged from 47.8% to 77.7% for olodaterol and from 28.7% to 70.1% for indacaterol. The remaining new users of olodaterol and indacaterol were classified as potential off-label users, with prevalence ranging from 17.3% to 48.6% for olodaterol and from 20.5% to 66.6% for indacaterol. This study provides no evidence of a major concern in Europe for olodaterol or indacaterol for off-label use in asthma or for pediatric use.
Development of Tripolymeric Triaxial Electrospun Fibrous Matrices for Dual Drug Delivery Applications
Authors: Nagiah Naveen , Murdock Christopher J. , Bhattacharjee Maumita , Nair Lakshmi , Laurencin Cato T. 
Published: January 2020

AbstractSince the first work by Laurencin and colleagues on the development of polymeric electrospinning for biomedical purposes, the use of electrospinning technology has found broad applications in such areas of tissue regeneration and drug delivery. More recently, coaxial electrospinning has emerged as an important technique to develop scaffolds for regenerative engineering incorporated with drug(s). However, the addition of a softer core layer leads to a reduction in mechanical properties. Here, novel robust tripolymeric triaxially electrospun fibrous scaffolds were developed with a polycaprolactone (PCL) (core layer), a 50:50 poly (lactic-co-glycolic acid) (PLGA) (sheath layer) and a gelatin (intermediate layer) with a dual drug delivery capability was developed through modified electrospinning. A sharp increase in elastic modulus after the incorporation of PCL in the core of the triaxial fibers in comparison with uniaxial PLGA (50:50) and coaxial PLGA (50:50) (sheath)-gelatin (core) fibers was observed. Thermal analysis of the fibrous scaffolds revealed an interaction between the core-intermediate and sheath-intermediate layers of the triaxial fibers contributing to the higher tensile modulus. A simultaneous dual release of model small molecule Rhodamine B (RhB) and model protein Fluorescein isothiocynate (FITC) Bovine Serum Albumin (BSA) conjugate incorporated in the sheath and intermediate layers of triaxial fibers was achieved. The tripolymeric, triaxial electrospun systems were seen to be ideal for the support of mesenchymal stem cell growth, as shrinkage of fibers normally found with conventional electrospun systems was minimized. These tripolymeric triaxial electrospun fibers that are biomechanically competent, biocompatible, and capable of dual drug release are designed for regenerative engineering and drug delivery applications.
Early-Onset Osteoarthritis originates at the chondrocyte level in Hip Dysplasia
Authors: Hernandez Paula A. , Wells Joel , Usheva Emiliya , Nakonezny Paul A. , Barati Zahra , Gonzalez Roberto , Kassem Layla , Henson Frances M. D. 
Published: January 2020

AbstractSubjects with developmental dysplasia of the hip (DDH) often show early-onset osteoarthritis (OA); however, the molecular mechanisms underlying this pathology are not known. We investigated whether cellular changes in chondrocytes from OA cartilage can be detected in chondrocytes from DDH cartilage before histological manifestations of degeneration. We characterized undamaged and damaged articular cartilage from 22 participants having hip replacement surgery with and without DDH (9 DDH-OA, 12 OA-only, one femoral fracture). Tissue immunostaining revealed changes in damaged OA-only cartilage that was also found in undamaged DDH-OA cartilage. Chondrocytes in situ from both groups show: (i) thicker fibers of vimentin intermediate filaments, (ii) clusters of integrin α5β1, (iii) positive MMP13 staining and (iv) a higher percentage of cells expressing the serine protease HtrA1. Further characterization of the extracellular matrix showed strong aggrecan and collagen II immunostaining in undamaged DDH cartilage, with no evidence of augmented cell death by activation of caspase 3. These findings suggest that early events in DDH cartilage originate at the chondrocyte level and that DDH cartilage may provide a novel opportunity to study these early changes for the development of therapeutic targets for OA.