bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased rhinovirus replication in nasal mucosa cells in allergic subjects is associated with increased ICAM‐1 levels and endosomal acidification and is inhibited by L‐carbocisteine
Authors: Yamaya Mutsuo , Nomura Kazuhiro , Arakawa Kazuya , Nishimura Hidekazu , Lusamba Kalonji Nadine , Kubo Hiroshi , Nagatomi Ryoichi , Kawase Tetsuaki 
Published: April 2016

AbstractIncreased viral replication and cytokine production may be associated with the pathogenesis of asthma attacks in rhinovirus (RV) infections. However, the association between increased RV replication and enhanced expression of intercellular adhesion molecule‐1 (ICAM‐1), a receptor for a major RV group, in airway epithelial cells has remained unclear. Furthermore, the inhibitory effects of mucolytics, which have clinical benefits in asthmatic subjects, are uncertain. Human nasal epithelial (HNE) cells were infected with type 14 rhinovirus (RV14), a major RV group. RV14 titers and cytokine concentrations, including interleukin (IL)‐6 and IL‐8, in supernatants, RV14 RNA replication and susceptibility to RV14 infection were higher in HNE cells obtained from subjects in the allergic group (allergic subjects) than in those from subjects in the non‐allergic group (non‐allergic subjects). ICAM‐1 expression and the number and fluorescence intensity of acidic endosomes from which RV14 RNA enters the cytoplasm were higher in HNE cells from allergic subjects, though substantial amounts of interferon (IFN)‐γ and IFN‐λ were not detected in the supernatant. The abundance of p50 and p65 subunits of transcription factor nuclear factor kappa B (NF‐κB) in nuclear extracts of the cells from allergic subjects was higher compared to non‐allergic subjects, and an inhibitor of NF‐κB, caffeic acid phenethyl ester, reduced the fluorescence intensity of acidic endosomes as well as RV titers and RNA. Furthermore, a mucolytic agent, L‐carbocisteine, reduced RV14 titers and RNA levels, cytokine release, ICAM‐1 expression, the fluorescence intensity of acidic endosomes, and NF‐κB activation. The increased RV14 replication observed in HNE cells from allergic subjects might be partly associated with enhanced ICAM‐1 expression and decreased endosomal pH through NF‐κB activation. L‐Carbocisteine inhibits RV14 infection by reducing ICAM‐1 and acidic endosomes and may, therefore, modulate airway inflammation caused by RV infection in allergic subjects.
Neuroglial alterations in the zebrafish brain exposed to cadmium chloride
Authors: Monaco Antonio , Grimaldi Maria C. , Ferrandino Ida 
Published: April 2016

AbstractCadmium is an extremely toxic heavy metal that widely occurs in industrial workplaces with various hazardous effects on brain functions. The cytotoxic effects of cadmium chloride (CdCl2) on the neuroglial components of the zebrafish brain were analysed by detecting the glial fibrillary acidic protein (GFAP) expression and the mRNA levels of myelin genes mbp, mpz and plp1 in adult specimens exposed to cadmium for 2, 7 and 16 days. A significant decrease in the GFAP protein by Western blotting experiments was observed after 2 days of treatment, reaching 55% after 16 days. No change was observed in the mRNA levels. Using immunohistochemistry, a reduction in GFAP‐positive structures was revealed with a progressive trend in all the brains at 2, 7 and 16 days of treatment. In particular, a considerable reduction in GFAP‐positive fibres, with a different course, was observed in the ventricle areas and at the pial surface and in blood vessels after 16 days. Our experiments also showed a structural and chemical alteration of myelin and upregulation of mpz mRNA levels, the oligodendrocyte gene that is upregulated in experiments of neuronal injury, but not of plp1 and mbp mRNA levels, other myelin structural genes. These data confirm the toxic action of cadmium on the zebrafish brain. This action is time‐dependent and involves the glial cells, key components of the protection and function of nerve cells, hence the basis for many neurological diseases. Copyright © 2016 John Wiley & Sons, Ltd.
Peroxide cross‐linked UHMWPE blended with vitamin E
Authors: Oral Ebru , Doshi Brinda N. , Gul Rizwan M. , Neils Andrew L. , Kayandan Sanem , Muratoglu Orhun K. 
Published: April 2016

AbstractRadiation crosslinked ultrahigh molecular weight polyethylene (UHMWPE) is the bearing surface material most commonly used in total joint arthroplasty because of its excellent wear resistance. Crosslinking agents such as peroxides can also effectively increase wear resistance but peroxide crosslinked UHMWPE has low oxidative stability. We hypothesized that the addition of an antioxidant to peroxide crosslinked UHMWPE could improve its oxidation resistance and result in mechanical, tribological, and oxidative properties equivalent to currently utilized radiation crosslinked UHMWPEs. Various vitamin E (0.1–1.0 wt % and peroxide concentration (0.5–1.5 wt %) combinations were studied to investigate changes in crosslink density, wear rate, mechanical properties, and oxidative stability in comparison to radiation crosslinked UHMWPE. Peroxide crosslinking was more efficient as compared to radiation crosslinking in the presence of vitamin E with the former resulting in lower wear rate with vitamin E concentrations above 0.3 wt %. The tensile mechanical properties were comparable to and the impact strength was higher than those of the clinically relevant radiation crosslinked controls. We also determined that gamma sterilization of peroxide crosslinked vitamin E blends improved wear resistance further. In summary, peroxide crosslinking of vitamin E‐blended UHMWPE may provide a feasible and economical alternative to radiation for achieving clinically relevant properties for total joint implants using UHMWPE. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1379–1389, 2017.
Probabilistic evaluation of the material properties of the in vivo subject‐specific articular surface using a computational model
Authors: Kang Kyoung‐Tak , Kim Sung‐Hwan , Son Juhyun , Lee Young Han , Kim Shinil , Chun Heoung‐Jae 
Published: April 2016

AbstractThis article used probabilistic analysis to evaluate material properties of the in vivo subject‐specific tibiofemoral (TF) joint model. Sensitivity analysis, based on a Monte Carlo (MC) method, was performed using a subject‐specific finite element (FE) model generated from in vivo computed tomography (CT) and magnetic resonance imaging (MRI) data, subjected to two different loading conditions. Specifically, the effects of inherent uncertainty in ligament stiffness, horn attachment stiffness, and articular surface material properties were assessed using multifactorial global sensitivity analysis. The MRI images were taken before and after axial compression, and when the flexion condition had been maintained at up to 90 degree flexion in the subject‐specific knee joint. The loading conditions of the probabilistic subject‐specific FE model (axial compression and 90 degree flexion) were similar to the MRI acquisition setup. We were able to detect the influence of material parameters while maintaining the potential effect of parametric interactions. Throughout the in silico property optimization, a subject‐specific FE model was used and less sensitive parameters were eliminated in the global sensitivity method. Soft tissue material properties were estimated using an optimization procedure that involved the minimization of the differences between the kinematics predicted by the subject‐specific model and those obtained through in vivo subject‐specific data. The results of this approach suggest that the articular surface mechanical properties could be found by using in vivo measurements, which clarifies the valuable tool for future subject‐specific studies related to TF joint scaffolds, allografts and biologics. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1390–1400, 2017.
Determination of joint loads using new sensate scaffolds for regenerating large cartilage defects in the knee
Authors: Szivek John A. , Ruth John T. , Heden Greg J. , Martinez Michael A. , Diggins Nicklaus H. , Wenger Karl H. 
Published: April 2016

AbstractTwo complete unicondylar surface replacement scaffold designs to support tissue‐engineered cartilage growth that utilized adult endogenous stem cells were 3D printed and tested in a dog stifle model. Integrated rosette strain gauges were calibrated and used to determine shear loading within stifle joints for up to 12 months. An activity index that compared extent of daily activity with tissue formation showed differences in the extent and quality of new tissue with the most active animal having the most new tissue formation. Shear loads were highest early and decreased with time indicating that cartilage tissue formation begins while tissues experience high shear loads and continues as the loads decrease toward normal physiological levels. Scaffolds with biomimetic support pegs facilitated the most rapid bone ingrowth and were noted to have more cartilage formation with better quality cartilage as measured using both indentation testing and histology. Comparison of implant placement depth to previous studies suggested that placement depth affects the amount of tissue formation. This study provides measurements of loading patterns and cartilage regeneration on a complete medial condylar surface replacement that can be used for preclinical testing of a tissue engineering approach for the most common form of early stage osteoarthritis, unicondylar disease. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1409–1421, 2017.
Macrophage Migration Inhibitory Factor (MIF) Supports Homing of Osteoclast Precursors to Peripheral Osteolytic Lesions
Authors: Movila Alexandru , Ishii Takenobu , Albassam Abdullah , Wisitrasameewong Wichaya , Howait Mohammed , Yamaguchi Tsuguno , Ruiz-Torruella Montserrat , Bahammam Laila , Nishimura Kazuaki , Van Dyke Thomas , Kawai Toshihisa 
Published: April 2016

ABSTRACT

By binding to its chemokine receptor CXCR4 on osteoclast precursor cells (OCPs), it is well known that stromal cell-derived factor-1 (SDF-1) promotes the chemotactic recruitment of circulating OCPs to the homeostatic bone remodeling site. However, the engagement of circulating OCPs in pathogenic bone resorption remains to be elucidated. The present study investigated a possible chemoattractant role of macrophage migration inhibitory factor (MIF), another ligand for C-X-C chemokine receptor type 4 (CXCR4), in the recruitment of circulating OCPs to the bone lytic lesion. To accomplish this, we used Csf1r-eGFP-knock-in (KI) mice to establish an animal model of polymethylmethacrylate (PMMA) particle-induced calvarial osteolysis. In the circulating Csf1r-eGFP+ cells of healthy Csf1r-eGFP-KI mice, Csf1r+/CD11b+ cells showed a greater degree of RANKL-induced osteoclastogenesis compared to a subset of Csf1r+/RANK+ cells in vitro. Therefore, Csf1r-eGFP+/CD11b+ cells were targeted as functionally relevant OCPs in the present study. Although expression of the two cognate receptors for MIF, CXCR2 and CXCR4, was elevated on Csf1r+/CD11b+ cells, transmigration of OCPs toward recombinant MIF in vitro was facilitated by ligation with CXCR4, but not CXCR2. Meanwhile, the level of PMMA-induced bone resorption in calvaria was markedly greater in wild-type (WT) mice compared to that detected in MIF-knockout (KO) mice. Interestingly, in contrast to the elevated MIF, diminished SDF-1 was detected in a particle-induced bone lytic lesion of WT mice in conjunction with an increased number of infiltrating CXCR4+ OCPs. However, such diminished SDF-1 was not found in the PMMA-injected calvaria of MIF-KO mice. Furthermore, stimulation of osteoblasts with MIF in vitro suppressed their production of SDF-1, suggesting that MIF can downmodulate SDF-1 production in bone tissue. Systemically administered anti-MIF neutralizing monoclonal antibody (mAb) inhibited the homing of CXCR4+ OCPs, as well as bone resorption, in the PMMA-injected calvaria, while increasing locally produced SDF-1. Collectively, these data suggest that locally produced MIF in the inflammatory bone lytic site is engaged in the chemoattraction of circulating CXCR4+ OCPs. © 2016 American Society for Bone and Mineral Research.
Increased EPO Levels Are Associated With Bone Loss in Mice Lacking PHD2 in EPO-Producing Cells
Authors: Rauner Martina , Franke Kristin , Murray Marta , Singh Rashim Pal , Hiram-Bab Sahar , Platzbecker Uwe , Gassmann Max , Socolovsky Merav , Neumann Drorit , Gabet Yankel , Chavakis Triantafyllos , Hofbauer Lorenz C , Wielockx Ben 
Published: April 2016

ABSTRACT

The main oxygen sensor hypoxia inducible factor (HIF) prolyl hydroxylase 2 (PHD2) is a critical regulator of tissue homeostasis during erythropoiesis, hematopoietic stem cell maintenance, and wound healing. Recent studies point toward a role for the PHD2-erythropoietin (EPO) axis in the modulation of bone remodeling, even though the studies produced conflicting results. Here, we used a number of mouse strains deficient of PHD2 in different cell types to address the role of PHD2 and its downstream targets HIF-1α and HIF-2α in bone remodeling. Mice deficient for PHD2 in several cell lineages, including EPO-producing cells, osteoblasts, and hematopoietic cells (CD68:cre-PHD2f/f) displayed a severe reduction of bone density at the distal femur as well as the vertebral body due to impaired bone formation but not bone resorption. Importantly, using osteoblast-specific (Osx:cre-PHD2f/f) and osteoclast-specific PHD2 knock-out mice (Vav:cre- PHD2f/f), we show that this effect is independent of the loss of PHD2 in osteoblast and osteoclasts. Using different in vivo and in vitro approaches, we show here that this bone phenotype, including the suppression of bone formation, is directly linked to the stabilization of the α-subunit of HIF-2, and possibly to the subsequent moderate induction of serum EPO, which directly influenced the differentiation and mineralization of osteoblast progenitors resulting in lower bone density. Taken together, our data identify the PHD2:HIF-2α:EPO axis as a so far unknown regulator of osteohematology by controlling bone homeostasis. Further, these data suggest that patients treated with PHD inhibitors or EPO should be monitored with respect to their bone status. © 2016 American Society for Bone and Mineral Research.
Value of higher‐resolution MRI in assessing middle cerebral atherosclerosis and predicting capsular warning syndrome
Authors: Xu Xin , Wei Yafen , Zhang Xiandong , Yang Lili , Cui Zhitang , Yan Junjie 
Published: April 2016

PurposeTo investigate the correlation between middle cerebral atherosclerosis and capsular warning syndrome (CWS) and assess the value of higher‐resolution magnetic resonance imaging (MRI) in prognostication.Materials and MethodsIn all, 97 transient ischemic attack (TIA) patients who underwent an MRI from February 2010 to December 2013 were included in the retrospective study and divided into either a CWS or middle cerebral artery (MCA) TIA group according to their eventual clinical diagnosis. 3T MRI included fast‐spin echo T2‐weighted imaging, double‐inverse recovery T1‐weighted imaging, and T1 contrast‐enhanced scan sequences. Baseline characteristics, MRI results in terms of MCA plaque formation, plaque characteristics such as enhancement, and development of infarction were compared between the two groups to study the distribution and characteristics of cerebral atherosclerotic plaques. Multivariate analysis identified factors associated with infarction 1 week after plaque identification.ResultsBased on the MR images, 76% of both groups of patients had middle cerebral atherosclerosis. Compared to TIA patients, the median age of CWS patients was younger (58 [range 42–73] vs. 67 [36–84] years, P = 0.003), and CWS patients had a lower rate of stroke history (10.9% vs. 41.2%, P = 0.001). Infarction was more common in CWS patients than in TIA patients (52.2% vs. 20.5%, P = 0.003) and a superior plaque was correlated with infarction occurrence (odds ratio 5.674, 95% confidence interval 1.112–28.958).ConclusionPatients with CWS have large arterial plaques, including MCA plaques. There was a correlation between CWS and the MCA plaque location. J. Magn. Reson. Imaging 2016;44:1277–1283.
MRI assessment of regional differences in phosphorus‐31 metabolism and morphological abnormalities of the foot muscles in diabetes
Authors: Lin Yu‐Ching , Wu Jim , Baltzis Dimitrios , Veves Aristidis , Greenman Robert 
Published: April 2016

PurposeTo assess differences in the phosphorus‐31 (31P) metabolism and morphology in multiple muscle regions in the forefoot of diabetic patients and normal subjects.Materials and MethodsFifteen diabetic patients and 15 normal subjects were assessed for muscle atrophy by 1H magnetic resonance imaging (MRI) at 3T to grade the flexor hallucis, adductor hallucis, interosseous regions, and entire foot cross‐section. Each region and the entire foot were also quantitatively evaluated for metabolic function using 31P imaging for spatial mapping of the inorganic phosphate (Pi) to phosphocreatine (PCr) ratio (Pi/PCr). The ratio of viable muscle area to the predefined region areas (31P/1H) was calculated. The variability of each method was assessed by its coefficient of variation (CV).ResultsMuscle atrophy was significantly more severe in diabetic compared to normal subjects in all regions (P < 0.01). The 31P/1H area ratio was significantly larger in the adductor hallucis than in the other two regions (P < 0.05). The Pi/PCr ratio was significantly different between the two groups in the flexor hallucis and interosseous regions (P < 0.05) but not adductor hallucis region. The CV for Pi/PCr ranged from 10.13 to 55.84, while it ranged from 73.40 to 263.90 for qualitative grading.ConclusionChanges in atrophy and metabolism appear to occur unequally between different regions of the forefoot in diabetes. The adductor hallucis region appears more capable of maintaining structural and metabolic integrity than the flexor hallucis or interosseous regions. The CV analysis suggests that the quantitative 31P methods have less variability than the qualitative grading. J. Magn. Reson. Imaging 2016;44:1132–1142.
Intratumor partitioning and texture analysis of dynamic contrast‐enhanced (DCE)‐MRI identifies relevant tumor subregions to predict pathological response of breast cancer to neoadjuvant chemotherapy
Authors: Wu Jia , Gong Guanghua , Cui Yi , Li Ruijiang 
Published: April 2016

PurposeTo predict pathological response of breast cancer to neoadjuvant chemotherapy (NAC) based on quantitative, multiregion analysis of dynamic contrast enhancement magnetic resonance imaging (DCE‐MRI).Materials and MethodsIn this Institutional Review Board‐approved study, 35 patients diagnosed with stage II/III breast cancer were retrospectively investigated using 3T DCE‐MR images acquired before and after the first cycle of NAC. First, principal component analysis (PCA) was used to reduce the dimensionality of the DCE‐MRI data with high temporal resolution. We then partitioned the whole tumor into multiple subregions usingk‐means clustering based on the PCA‐defined eigenmaps. Within each tumor subregion, we extracted four quantitative Haralick texture features based on the gray‐level co‐occurrence matrix (GLCM). The change in texture features in each tumor subregion between pre‐ and during‐NAC was used to predict pathological complete response after NAC.ResultsThree tumor subregions were identified through clustering, each with distinct enhancement characteristics. In univariate analysis, all imaging predictors except one extracted from the tumor subregion associated with fast washout were statistically significant (P< 0.05) after correcting for multiple testing, with area under the receiver operating characteristic (ROC) curve (AUC) or AUCs between 0.75 and 0.80. In multivariate analysis, the proposed imaging predictors achieved an AUC of 0.79 (P= 0.002) in leave‐one‐out cross‐validation. This improved upon conventional imaging predictors such as tumor volume (AUC = 0.53) and texture features based on whole‐tumor analysis (AUC = 0.65).ConclusionThe heterogeneity of the tumor subregion associated with fast washout on DCE‐MRI predicted pathological response to NAC in breast cancer. J. Magn. Reson. Imaging 2016;44:1107–1115.
Numbing of Positive, Negative, and General Emotions: Associations With Trauma Exposure, Posttraumatic Stress, and Depressive Symptoms Among Justice‐Involved Youth
Authors: Kerig Patricia K. , Bennett Diana C. , Chaplo Shannon D. , Modrowski Crosby A. , McGee Andrew B. 
Published: April 2016

AbstractIncreasing attention has been drawn to the symptom of emotional numbing in the phenomenology of posttraumatic stress disorder (PTSD), particularly regarding its implications for maladaptive outcomes in adolescence such as delinquent behavior. One change in the definition of emotional numbing according to the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM‐5; American Psychiatric Association, 2013) was the limitation to the numbing of positive emotions. Previous research with youth, however, has implicated general numbing or numbing of negative emotions in PTSD, whereas numbing of positive emotions may overlap with other disorders, particularly depression. Consequently, the goal of this study was to investigate whether numbing of positive emotions was associated with PTSD symptoms above and beyond numbing of negative emotions, general emotional numbing, or depressive symptoms among at‐risk adolescents. In a sample of 221 detained youth (mean age = 15.98 years, SD = 1.25; 50.7% ethnic minority), results of hierarchical multiple regressions indicated that only general emotional numbing and numbing of anger accounted for significant variance in PTSD symptoms (total R2 = .37). In contrast, numbing of sadness and positive emotions were statistical correlates of depressive symptoms (total R2 = .24). Further tests using Hayes’ Process macro showed that general numbing, 95% CI [.02, .45], and numbing of anger, 95% CI [.01, .42], demonstrated indirect effects on the association between trauma exposure and PTSD symptoms.
Hydrological Connectivity Does Change Over 70 Years of Abandonment and Afforestation in the Spanish Pyrenees
Authors: López‐Vicente Manuel , Nadal‐Romero Estela , Cammeraat Erik L. H. 
Published: April 2016

AbstractRunoff connectivity depends on topography, rainfall, man‐made elements (terraces, trails, roads and drainage systems) and vegetation. In this study, we quantified the effects of 70 years of human activities on runoff connectivity in the mountainous Araguás afforested sub‐catchment (17·2 ha; Central Spanish Pyrenees). The IC index of hydrological connectivity was chosen to perform this metric over six land use scenarios at high spatial resolution (1 × 1 m of cell size). The current scenario (year 2012) was simulated with three flow accumulation algorithms (MD, MD8 and D8). MD8 was linked with the most frequent hydrological response of the sub‐catchment (rainfall intensity and stream flow during 7 years) and generated the most representative pattern of connectivity, especially in the linear landscape elements (LLE). This algorithm was chosen to simulate five past scenarios (1945, 1956, 1973, 1980 and 2006). In all scenarios, the highest connectivity appeared related to trails and roads, as well as to streams and gullies, whereas the lowest appeared related to stonewalls in 1945 and 1956 to hillslopes in 1973, and the following afforestation. Changes in connectivity mainly depended on the changes in the vegetation factor and in a minor way in the total length, spatial location and type of LLE. Afforestation promoted lower and more stable connectivity at both local and catchment scales. Copyright © 2016 John Wiley & Sons, Ltd.