bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dose‐Dependent Cannabidiol‐Induced Elevation of Intracellular Calcium and Apoptosis in Human Articular Chondrocytes
Authors: Winklmayr Martina , Gaisberger Martin , Kittl Michael , Fuchs Julia , Ritter Markus , Jakab Martin 
Published: August 2019

ABSTRACTCannabidiol (CBD) is the most abundant non‐psychoactive compound of Cannabis sativa extracts. Cannabinoids have been shown to exhibit anti‐inflammatory, analgesic, antioxidant, neuroprotective, and anti‐tumorigenic effects. In the present study, we investigated the effects of CBD on human articular chondrocytes. Cell viability was determined by Resazurin assays. Apoptosis was analyzed by annexin‐V/7‐actinomycin D (7‐AAD) staining followed by flow cytometry. Caspase 3/7 activity was measured with caspase assays. Intracellular Ca2+ ([Ca2+]i) was monitored by time‐lapse fluorescence imaging. The perforated whole‐cell patch‐clamp technique was used for measuring the cell membrane potential. Erk1/2 phosphorylation was assessed by western blot analysis. The chondrocyte cell line C28/I2 and primary chondrocytes showed a reduced viability after treatment with concentrations of CBD greater than 4 µM. This apoptotic effect was accompanied by an increase of caspase 3/7 activity and an increase in the early apoptotic cell population. CBD elevated [Ca2+]i, which was accompanied by depolarization of the cell membrane potential. The increase of [Ca2+]i was abrogated, when Ca2+ was omitted from the bath solution, indicating an influx of extracellular Ca2+. The cannabinoid receptor 1 (CB1) antagonist AM251 inhibited the Ca2+ influx triggered by CBD. Preincubation with AM251 reduced the toxic effects of CBD. By looking for mediators of the apoptotic CBD effect downstream of the CB1 receptor, enhanced Erk1/2 phosphorylation could be detected after CBD treatment. However, this Erk1/2 activation proved to be unaffected by CB1 receptor blockage. The present study demonstrates that CBD promotes apoptosis and [Ca2+]i elevation in human articular chondrocytes via a CB1‐receptor‐mediated mechanism. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society J Orthop Res 37:2540–2549, 2019
Identification of Inflammatory Mediators in Tendinopathy Using a Murine Subacromial Impingement Model
Authors: Eliasberg Claire D. , Wada Susumu , Carballo Camila B. , Nakagawa Yusuke , Nemirov Daniel A. , Bhandari Reyna , Otero Miguel , Deng Xiang‐Hua , Rodeo Scott A. 
Published: August 2019

ABSTRACTSubacromial impingement is associated with a spectrum of disorders—including rotator cuff disease—but their relationship is complex. We have established a novel murine model of subacromial impingement to study supraspinatus tendinopathy. The purpose of this study was to evaluate changes in gene expression in this murine shoulder impingement model to further elucidate the mechanisms underlying the development of tendinopathy. Twenty‐eight C57BL/6 mice were used in this study. All mice underwent bilateral surgery with insertion of a small metal clip in the subacromial space or a sham procedure. The supraspinatus tendons underwent histological analyses, biomechanical testing, and RNA extraction for multiplex gene expression analysis (NanoString, Seattle, WA). Histology demonstrated increased cellularity and disorganized collagen fibers of the supraspinatus tendon in the clip impingement group. Mean load to failure (5.20 vs. 1.50 N, p < 0.001) and mean stiffness (4.95 vs. 1.47 N/mm, p < 0.001) were lower in the impingement group than the sham group. NanoString analyses revealed 111 differentially expressed genes (DEGs) between the impingement and sham groups. DEGs of interest included Mmp3 (expression ratio [ER]: 2.68, p = 0.002), Tgfb1 (ER: 1.76, p = 0.01), Col3a1 (ER: 1.66, p = 0.03), and Tgfbr2 (ER: 1.53, p = 0.01). Statement of clinical significance: We identified 111 DEGs that may contribute to the development of tendinopathy in this model. Further studies of these specific genes will allow identification of their roles in the initiation and regulation of tendon damage, and their potential to serve as novel therapeutic targets in the treatment of rotator cuff disease. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2575–2582, 2019
Time analysis of alveolar ridge preservation using a combination of mineralized bone‐plug and dense‐polytetrafluoroethylene membrane: A histomorphometric study
Authors: Wen Shih‐Cheng , Barootchi Shayan , Huang Wen‐Xia , Wang Hom‐Lay 
Published: August 2019

AbstractBackgroundThe objective of this study was to histologically evaluate and compare vital bone formation, residual graft particles, and fraction of connective tissue (CT)/other tissues between three different time points at 2‐month intervals after alveolar ridge preservation with a cancellous allograft and dense‒polytetrafluoroethylene (d‐PTFE) membrane.MethodsRidge preservation with a cancellous allograft and d‐PTFE membrane was performed at 49 extraction sockets (one per patient). Volunteers were assigned to implant placement at three different time points of 2, 4, and 6 months, at which time core biopsies were obtained. Histomorphometric analysis was performed to determine the percentages of vital bone, residual graft particles, and connective tissue/other non‐bone components, and subjected to statistical analyses.ResultsThere was a statistically significant difference in the amount of vital bone at every time point from 28.31% to 40.87% to 64.11% (at 2‐, 4‐, and 6‐month groups, respectively) (P < 0.05). The percentage of residual graft particles ranged from 44.57% to 36.16% to 14.86%, showing statistical significance from 4 to 6 months (21.29%, P < 0.001), and 2 to 6 months (29.71%, P < 0.001), while there were no significant differences for the amount of CT/other tissue among the different time points.ConclusionsThis study provided the first histologic comparison of alveolar ridge preservation using a cancellous allograft and d‐PTFE membrane at three different time points. Extraction sockets that healed for 6 months produced the highest amount of vital bone in combination with the least percentage of residual graft particles, while similar results were observed for the fraction of CT/other tissues between the three time points.
Novel rare frameshift variation in aggressive periodontitis: Exomic and familial‐screening analysis
Authors: Taiete Tiago , Casati Marcio Z. , Martins Luciane , Andia Denise C. , Mofatto Luciana S. , Coletta Ricardo D. , Monteiro Mabelle F. , Araújo Cássia F. , Santamaria Mauro P. , Corrêa Mônica G. , Sallum Enilson A. , Nociti Francisco H. , Casarin Renato C. 
Published: August 2019

AbstractBackgroundAggressive periodontitis (AgP), currently periodontitis grade C, presents early onset, rapid progression, and a poorly established genetic association. Thus, this study aimed to identify genetic variants associated with AgP via whole exome sequencing (WES) through a familial screening approach.MethodsWES was performed in two nuclear families, including a proband and a parent affected by AgP and an unaffected parent and sibling. Common variants among affected individuals, excluding those common to healthy people, from each family, composed the data set associated with AgP. In silico analysis evaluated the impact of each variant on protein structure and protein‐protein interactions. Moreover, identified deleterious variants were validated in a populational analysis (n = 96).ResultsThe missense single nucleotide variations (SNVs) rs142548867 in EEFSEC (c.668C>T), rs574301770 in ZNF136 (c.466C>G), and rs72821893 in KRT25 (c.800G>A) and the frameshift indels rs37146475 in GPRC6A (c.2323‐2324insT) and c.1366_1372insGGAGCAG in ELN were identified in AgP and have a predicted functional impact on proteins. In silico analysis indicated that the indel in GPRC6A generates a loss of the C‐terminal tail of the Gprca protein. Furthermore, this SNV was significantly associated with AgP in a population‐based investigation.ConclusionNovel frameshift variation in GPRC6A (c.2323‐2324insT) was identified as a potential genetic alteration associated with AgP occurrence.
Non‐cyanobacterial diazotrophs dominate nitrogen‐fixing communities in permafrost thaw ponds
Authors: Fernandez Leyden , Bertilsson Stefan , Peura Sari 
Published: August 2019

AbstractThere is a growing concern about the implications of accelerated thawing of permafrost for regional biogeochemical cycling of carbon and other bioreactive elements. One such element of concern is nitrogen, and in this study, we investigated the diversity and biogeography of potential diazotrophs within a series of thaw ponds representing different ontogenetic stages in pond development. Using metagenomic sequence data from subarctic thaw ponds, we identified an array of nitrogenase genes across the ponds. The iron‐only nitrogenase gene (anfH) was positively correlated with sulfate, while there was no correlation with methane despite previous findings that organisms carrying anfH can simultaneously participate in nitrogen fixation and methanogenesis. Sulfate is known to inhibit microbial uptake of molybdate, an element essential for the activity of the nifH (molybdenum‐iron) nitrogenase and this may explain the high potential for nitrogen fixation utilizing anfH in sulfate‐rich ponds. NifH was particularly abundant in the hypolimnion of the deeper and older ponds, with Deltaproteobacteria and Chlorobi as the putative dominant diazotrophs. In the epilimnetic waters, nifH composition was more variable, with various Gammaproteobacteria as abundant representatives, while cyanobacterial diazotrophs were scarce. Interestingly, nifH gene abundance was significantly positively correlated with in situ methane concentration. Based on genome‐resolved metagenomics, we hypothesize that diazotrophs and methanogens engage in syntrophic interactions in anoxic waters, possibly via propionate oxidation or (in Geobacter) by interspecies electron transfer. Our results also suggest that nitrogen fixers may supply bioreactive nitrogen compounds to the thaw pond communities, thereby enhancing growth and activity of methanogens.
A graphene‐based tunable negative refractive index metamaterial and its application in dynamic beam‐tilting terahertz antenna
Authors: Luo Yanbin , Zeng Qingsheng , Yan Xin , Jiang Tao , Yang Rongcao , Wang Jiayun , Wu Yong , Lu Qichao , Zhang Xia 
Published: August 2019

AbstractGraphene is emerging as a kind of promising 2D material in designing reconfigurable terahertz (THz) devices owning to its tunability of the surface conductivity, which can be tuned by changing the chemical potential. In this work, we demonstrated a graphene‐based THz tunable negative refractive index metamaterial. The proposed metamaterial unit consists of a metallic resonant structure and embedded graphene, which presents a dynamic negative refractive index in the corresponding bands by modulating the chemical potential of the embedded graphene. In addition, a dynamic beam‐tilting antenna loaded with the metamaterial‐based stacked configuration has been designed. Through changing the refractive index of the metamaterial or the number of layers in the stacked configuration, the steering angle can be adjusted from 0° to −27°. This work demonstrates the great potential of graphene in THz tunable negative refractive index materials, provides a classic case about the practical application of controllable negative refractive index, and also gives an effective way to design dynamic beam‐tilting antenna.
Determination of 3D PSFs from computed tomography reconstructed x‐ray images of spherical objects and the effects of sphere radii
Authors: Robert Normand , Mainprize James G. , Whyne Cari 
Published: August 2019

PurposeA method was developed to obtain three‐dimensional (3D) point spread functions (PSFs) of reconstructed x‐ray volumetric images using spheres of known diameters. The algorithm consists of a sphere localization step using template matching applied to the entire volume. Richardson Lucy (RL) deconvolution is used atypically to determine the PSF from the reconstructed x‐ray image and a model of the sphere. The resulting PSF is arbitrary, that is, there are no assumptions of separability or symmetry. Oversampling is not used, and sample spacing matches the image. The effect of sphere radius on PSF estimate reproducibility is investigated.MethodsPhantoms were constructed by suspending five polytetrafluoroethylene (PTFE) spheres having known radii equal to 4.77, 7.95, 9.52, 12.68, and 19.53 mm in an agar solution. The phantom included a 25 μm steel wire to calculate a line spread function (LSF). The phantom was imaged and reconstructed with a Medtronic surgical O‐Arm 23 times and a Toshiba Aquilion One computed tomography (CT) 20 times. A sharp reconstruction kernel exhibiting a nonmonotonic PSF was used with the Toshiba CT. PSFs and LSFs were computed for all of the images and repeated estimates were used to compute mean and standard deviation values for every point of the PSFs and LSFs. The PSFs from spheres were converted to LSFs and compared to the wire LSF.ResultsThe standard deviations of the PSF estimates exhibit a decreasing trend as the sphere radius is increased. The PSF from the smallest 4.77 mm sphere is the least reproducible. The normalized root mean square difference between the mean LSF derived from the 4.77 mm radius sphere and the mean wire LSF is 2.0% for the O‐arm and 1.2% for the CT.ConclusionRichardson Lucy (RL) deconvolution provides a method to estimate generalized (no separability or other simplifying assumptions) 3D PSFs from spheres. X‐ray noise in images acquired with typical clinical protocols cause noticeable variations in PSF estimates which can be mitigated by selecting larger spheres and combining PSF estimates from different images.
Automated retinal lesion detection via image saliency analysis
Authors: Yan Qifeng , Zhao Yitian , Zheng Yalin , Liu Yonghuai , Zhou Kang , Frangi Alejandro , Liu Jiang 
Published: August 2019

Background and objectiveThe detection of abnormalities such as lesions or leakage from retinal images is an important health informatics task for automated early diagnosis of diabetic and malarial retinopathy or other eye diseases, in order to prevent blindness and common systematic conditions. In this work, we propose a novel retinal lesion detection method by adapting the concepts of saliency.MethodsRetinal images are first segmented as superpixels, two new saliency feature representations: uniqueness and compactness, are then derived to represent the superpixels. The pixel level saliency is then estimated from these superpixel saliency values via a bilateral filter. These extracted saliency features form a matrix for low‐rank analysis to achieve saliency detection. The precise contour of a lesion is finally extracted from the generated saliency map after removing confounding structures such as blood vessels, the optic disk, and the fovea. The main novelty of this method is that it is an effective tool for detecting different abnormalities at the pixel level from different modalities of retinal images, without the need to tune parameters.ResultsTo evaluate its effectiveness, we have applied our method to seven public datasets of diabetic and malarial retinopathy with four different types of lesions: exudate, hemorrhage, microaneurysms, and leakage. The evaluation was undertaken at the pixel level, lesion level, or image level according to ground truth availability in these datasets.ConclusionsThe experimental results show that the proposed method outperforms existing state‐of‐the‐art ones in applicability, effectiveness, and accuracy.
Digital tomosynthesis based digital volume correlation: A clinically viable noninvasive method for direct measurement of intravertebral displacements using images of the human spine under physiological load
Authors: Oravec Daniel , Flynn Michael J. , Zauel Roger , Rao Sudhaker , Yeni Yener N. 
Published: August 2019

PurposeWe have developed a clinically viable method for measurement of direct, patient‐specific intravertebral displacements using a novel digital tomosynthesis based digital volume correlation technique. These displacements may be used to calculate vertebral stiffness under loads induced by a patient's body weight; this is particularly significant because, among biomechanical variables, stiffness is the strongest correlate of bone strength. In this proof of concept study, we assessed the feasibility of the method through a preliminary evaluation of the accuracy and precision of the method, identification of a range of physiological load levels for which displacements are measurable, assessment of the relationship of measured displacements with microcomputed tomography based standards, and demonstration of the in vivo application of the technique.MethodsFive cadaveric T11 vertebrae were allocated to three groups in order to study (a) the optimization of digital volume correlation algorithm input parameters, (b) accuracy and precision of the method and the ability to measure displacements at a range of physiological load levels, and (c) the correlation between displacements measured using tomosynthesis based digital volume correlation vs. high resolution microcomputed tomography based digital volume correlation and large scale finite element models. Tomosynthesis images of one patient (Female, 60 yr old) were used to calculate displacement maps, and in turn stiffness, using images acquired in both standing and standing‐with‐weight (8 kg) configurations.ResultsWe found that displacements were accurate (2.28 µm total error) and measurable at physiological load levels (above 267 N) with a linear response to applied load. Calculated stiffness among three tested vertebral bodies was within an acceptable range relative to reported values for vertebral stiffness (5651‐13260 N/mm). Displacements were in good qualitative and quantitative agreement with both microcomputed tomography based finite element (r2 = 0.762, P < 0.001) and digital volume correlation (r2 = 0.799, P < 0.001) solutions. For one patient tested twice, once standing and once holding weights, results demonstrated excellent qualitative reproducibility of displacement distributions with superior endplate displacements increasing by 22% with added weight.ConclusionsThe results of this work collectively suggest the feasibility of the method for in vivo measurement of intravertebral displacements and stiffness in humans. These findings suggest that digital volume correlation using digital tomosynthesis imaging may be useful in understanding the mechanical response of bone to disease and may further enhance our ability to assess fracture risk and treatment efficacy for the spine.
Predicting Persistence of Rio Grande Cutthroat Trout Populations in an Uncertain Future
Authors: Zeigler Matthew P. , Rogers Kevin B. , Roberts James J. , Todd Andrew S. , Fausch Kurt D. 
Published: August 2019

Abstract
The Rio Grande Cutthroat Trout Oncorhynchus clarkii virginalis (RGCT) occupies just 12% of its ancestral range. As the southernmost subspecies of Cutthroat Trout, we expect a warming climate to bring additional stressors to RGCT populations, such as increased stream temperatures, reduced streamflows, and increased incidence of wildfire. We developed a Bayesian network (BN) model using site-specific data, empirical research, and expert knowledge to estimate the probability of persistence for each of the 121 remaining RGCT conservation populations and to rank the severity of the threats they face. These inputs quantified the genetic risks (e.g., inbreeding risk and hybridization risk), population demographics (disease risk, habitat suitability, and survival), and probability of stochastic disturbances (stream drying risk and wildfire risk) in an uncertain future. We also created stream temperature and base flow discharge models coupled with regionally downscaled climate projections to predict future abiotic conditions at short-term (2040s) and long-term (2080s) time horizons. In the absence of active management, we predicted a decrease in the average probability of population persistence from 0.53 (current) to 0.31 (2040s) and 0.26 (2080s). Only 11% of these populations were predicted to have a greater than 75% chance of persisting to the 2080s. Threat of invasion by nonnative trout had the strongest effect on population persistence. Of the 78 populations that are already invaded or lacking complete barriers, 60% were estimated to be extirpated by 2080 and the remainder averaged only a 10% chance of persistence. In contrast, the effects of increased stream temperatures were predicted to affect the future persistence of only 9% of the 121 RGCT populations remaining, as most have been restricted to high-elevation habitats that are cold enough to buffer against some stream warming. Our BN model provides a framework for evaluating threats and will be useful to guide management actions that are likely to provide the most benefit for long-term conservation.
Identification of guinea pig remains in the Pucará de Tilcara (Jujuy, Argentina): Evidence in favour of the presence of the Andean breed in the Quebrada de Humahuaca
Authors: Lopez Geronazzo Lautaro N. , Otero Clarisa , Álvarez Alicia , Ercoli Marcos D. , Cortés‐Delgado Natalia 
Published: August 2019

AbstractIn this article, we identified rodent remains found in the Pucará de Tilcara, an archaeological site from the Argentine Northwest that was occupied by humans from 1,100 aduntil the Spanish conquest. The zooarchaeological analyses were carried out using anatomical descriptions and geometric morphometric analyses of the dorsal and ventral views of mandibular remains. The results and the archaeological context discussed showed that all the rodent remains could correspond to the Andean breed of domestic guinea pigs. The combination of the methods used here gave us a strong support to the taxonomical assignment. The presence of domestic guinea pigs in archaeological sites of the northwestern Argentina was never proposed. This approach allowed us to increase knowledge about the distribution of caviines in the region, and their relationship to anthropic processes.
Tailoring block copolymer nanoporous thin films with acetic acid as a small guest molecule
Authors: Alvarez‐Fernandez Alberto , Valdes‐Vango Fernando , Martín José Ignacio , Vélez María , Quirós Carlos , Hermida‐Merino Daniel , Portale Giuseppe , Alameda José María , García Alonso Francisco Javier 
Published: August 2019

AbstractBlock copolymers offer the fabrication of mesoporous thin films with distinct nanoscale structural features. In this contribution, we present the use of acetic acid (CH3COOH) as a low‐molecular‐weight guest molecule to tune the supramolecular assembly of poly[styrene‐block‐(4‐vinylpyridine)] (PS‐b‐P4VP), offering a versatile and straightforward method to obtain tailored nanostructured films with controlled topography and pore size. Spin‐coating toluene solutions of PS‐b‐P4VP, with a variable amount of CH3COOH, leads to micellar thin films, where the micelles contain the carboxylic acid as a guest molecule. The size can be conveniently modified in these films (from 48 to 75 nm) by varying the amount of organic acid in the starting solutions. Subsequent surface reconstruction of micellar films using ethanol leads to ring‐shaped copolymer nanoporous films with modulated diameter. Controlling the micelle reconstruction process, cylindrical porous films are also obtained. Interestingly, changing the type of aliphatic carboxylic acid leads to a modification of the observed film morphology from micelles to out‐of‐plane P4VP cylinders (or lamellae) in a PS matrix. © 2019 Society of Chemical Industry