bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytotoxicity of PVPAC‐treated bovine pericardium: A potential replacement for glutaraldehyde in biological heart valves
Authors: Galvão Barros Janaina Aline , Filippin‐Monteiro Fabiola Branco , de Oliveira Edson Mendes , Campa Ana , Catalani Luiz Henrique , de Nogueira Moraes Pitombo Ronaldo , Polakiewicz Bronislaw 
Published: October 2013

AbstractAcellular biological tissues, including bovine pericardium (BP), have been proposed as biomaterial for tissue engineering. BP is usually modified chemically to improve mechanical and biological properties using glutaraldehyde, the standard reagent for preservation of fresh bioprosthetic materials. Glutaraldehyde‐fixed BP (Glut‐BP), the most widely used material in heart valve manufacture, has been associated with calcificationin vivo. In an attempt to reduce this issue and maintain its biocompatibility, this study assesses the physical properties and cytotoxicity of lyophilized BP treated with poly (vinylpyrrolidone‐co‐acrolein) (PVPAC‐BP), a novel copolymer, as a substitute for glutaraldehyde. For that, PVPAC‐BP surface ultrastructure, elastic function, water uptake and tissue calcification were evaluated. For the analysis of biocompatibility, fibroblasts (3T3‐L1) and endothelial cells (HUVEC) were cultured on PVPAC‐BP, Untreated‐BP and Glut‐BP. Nitric oxide (NO) release assay, fluorescence and SEM images of endothelial cells adhered on scaffolds were also performed. As results, the data show some advantages of PVPAC‐BP over the Glut‐BP. The PVPAC‐BP maintains partially the original ultrastructure and elastic properties, improves scaffold hydration, and presents less calcium phosphate deposits. The cells demonstrated strong attachment, high proliferation rate, and formation of a monolayer on PVPAC‐BP. Attached cells were also able to release NO de‐monstrating regular metabolism. In conclusion, PVPAC may be considered as a promising alternative to BP treatment improving the efficiency of cell attachment and proliferation and also avoid immunogenicity. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 574–582, 2014.
Hyaluronic acid colloidal gels as self‐assembling elastic biomaterials
Authors: Fakhari Amir , Phan Quang , Berkland Cory 
Published: October 2013

AbstractHyaluronic acid (HA) is a naturally occurring biodegradable polymer with a variety of applications in medicine. The use of HA as a filler or scaffold for regenerating tissues often requires improving the elastic properties of HA. This is conventionally accomplished via chemical crosslinking, which might require the generation of toxic free radicals. Although the mechanical properties of the resulting gel material can be tuned, these types of materials are static and susceptible to mechanical failure. The aim of this study was to develop a colloidal system for scaffold fabrication that is held together by physical interactions between HA nanoparticles. HA nanoparticles composed of 17 kDa HA suspended in water at different concentrations (15%, 30%, and 45% w/v, respectively) formed a stable three‐dimensional (3D) colloidal gel as a result of physical entanglement of free polymer chains on the surfaces of nanoparticles. The swelling ratio, shear moduli (G), compressive failure properties, and viscosity of colloidal gels were concentration dependent. The colloidal gels also were found to exhibit dynamic and recoverable properties, thus suggesting that these “self‐associating colloids” offer characteristics distinct arising from crosslinked polymers or high concentration colloids. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 612–618, 2014.
Is keratinized mucosa indispensable to maintain peri‐implant health? A systematic review of the literature
Authors: Brito Carlos , Tenenbaum Howard C. , Wong Benjamin K. C. , Schmitt Christian , Nogueira‐Filho Getulio 
Published: October 2013

AbstractThe significance of keratinized mucosa (KM) around dental implants is still not well explained and has been controversial. The aim of this systematic review was to evaluate the importance of KM around dental implants. The electronic databases Cochrane library, MEDLINE, EMBASE, and Virtual Health Library (VHL) databases were utilized to search original articles from 2006 to March 2013. The inclusion and exclusion criteria used to select the articles were: (1) Human studies published in the English language; (2) Study published in international peer‐viewed journals; (3) Studies evaluated the association between KM width and the peri‐implant tissue health; (4) Studies that have follow up of greater than 12 months; (5) Publication of studies not older than 10 years. The searches retrieved 285 citations. Seven articles fulfilled all of the inclusion criteria. Out of these, three studies were ranked as presenting high methodological quality, and four were judged to be of moderate quality. This systematic review concludes that the presence of an adequate zone of keratinized tissue may be necessary because it was shown to be related to better peri‐implant tissue health. Further randomized controlled trials are necessary to support this statement. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 643–650, 2014.
Vitamin D Supplementation After Parathyroidectomy: Effect on Bone Mineral Density—A Randomized Double-Blind Study
Authors: Norenstedt Sophie , Pernow Ylva , Zedenius Jan , Nordenström Jörgen , Sääf Maria , Granath Fredrik , Nilsson Inga-Lena 
Published: October 2013

ABSTRACT

Patients with primary hyperparathyroidism (PHPT) have higher bone turnover, lower bone mineral density (BMD), and an increased risk of fractures. They also have a high incidence of low vitamin D levels (25-OH-vitamin D &lt;50 nmol/L) that could worsen the negative effect on the bone. In this double-blinded clinical trial, 150 patients with PHPT were randomized, after successful parathyroidectomy (PTX), to 1-year daily treatment with either cholecalciferol 1600 IU and calcium carbonate 1000 mg (D +font-family:monospace or calcium carbonate alone (D–). BMD was measured in the lumbar spine, femoral neck, total hip, distal and 33% radius using dual-energy X-ray absorptiometry (DXA) before surgery and after 1 year of study medication. Median age was 60 (range 30–80) years and there were 119 (79%) women and 31 (21%) men; 76% had 25-OH-D &lt;50 nmol/L before PTX and 50% had persistent elevated parathyroid hormone (PTH) 6 weeks after PTX. A similar increase in BMD in the lumbar spine, femoral neck, and total hip was observed in both groups (D + : 3.6%, 3.2%, and 2.7%, p &lt; 0.001, respectively; and D–: 3.0%, 2.3%, and 2.1%, respectively, p &lt; 0.001). Patients with vitamin D supplementation also increased their BMD in distal radius (median 2.0%; interquartile range, −1.7% to 5.4%; p = 0.013). The changes in BMD, especially in the hips, were correlated to the baseline concentrations of PTH, ionized calcium, and bone markers (p &lt; 0.001). A benefit from vitamin D substitution was observed among patients with a persistent postoperative PTH elevation, who also improved their BMD at 33% radius and radius ultradistal (p &lt; 0.05). In conclusion, except for a minor improvement of radius BMD, our data show no beneficial effect on BMD or bone turnover markers of vitamin D supplementation after PTX. Preoperative PTH seems to have the strongest association with improvement in BMD. © 2014 American Society for Bone and Mineral Research.
In Vivo Assessment of Bone Quality in Postmenopausal Women With Type 2 Diabetes
Authors: Farr Joshua N , Drake Matthew T , Amin Shreyasee , Melton L Joseph , McCready Louise K , Khosla Sundeep 
Published: October 2013

ABSTRACT

Although patients with type 2 diabetes (T2D) are at significant risk for well-recognized diabetic complications, including macrovascular disease, retinopathy, nephropathy, and neuropathy, it is also clear that T2D patients are at increased risk for fragility fractures. Furthermore, fragility fractures in patients with T2D occur at higher bone mineral density (BMD) values compared to nondiabetic controls, suggesting abnormalities in bone material strength (BMS) and/or bone microarchitecture (bone “quality”). Thus, we performed in vivo microindentation testing of the tibia to directly measure BMS in 60 postmenopausal women (age range, 50–80 years) including 30 patients diagnosed with T2D for &gt;10 years and 30 age-matched, nondiabetic controls. Regional BMD was measured by dual-energy X-ray absorptiometry (DXA); cortical and trabecular bone microarchitecture was assessed from high-resolution peripheral quantitative computed tomography (HRpQCT) images of the distal radius and tibia. Compared to controls, T2D patients had significantly lower BMS: unadjusted (−11.7%; p &lt; 0.001); following adjustment for body mass index (BMI) (−10.5%; p &lt; 0.001); and following additional adjustment for age, hypertension, nephropathy, neuropathy, retinopathy, and vascular disease (−9.2%; p = 0.022). By contrast, after adjustment for confounding by BMI, T2D patients had bone microarchitecture and BMD that were not significantly different than controls; however, radial cortical porosity tended to be higher in the T2D patients. In addition, patients with T2D had significantly reduced serum markers of bone turnover (all p &lt; 0.001) compared to controls. Of note, in patients with T2D, the average glycated hemoglobin level over the previous 10 years was negatively correlated with BMS (r = −0.41; p = 0.026). In conclusion, these findings represent the first demonstration of compromised BMS in patients with T2D. Furthermore, our results confirm previous studies demonstrating low bone turnover in patients with T2D and highlight the potential detrimental effects of prolonged hyperglycemia on bone quality. Thus, the skeleton needs to be recognized as another important target tissue subject to diabetic complications. © 2014 American Society for Bone and Mineral Research.
NF-κB RelB Negatively Regulates Osteoblast Differentiation and Bone Formation
Authors: Yao Zhenqiang , Li Yanyun , Yin Xiaoxiang , Dong Yufeng , Xing Lianping , Boyce Brendan F 
Published: October 2013

ABSTRACT

RelA-mediated NF-κB canonical signaling promotes mesenchymal progenitor cell (MPC) proliferation, but inhibits differentiation of mature osteoblasts (OBs) and thus negatively regulates bone formation. Previous studies suggest that NF-κB RelB may also negatively regulate bone formation through noncanonical signaling, but they involved a complex knockout mouse model, and the molecular mechanisms involved were not investigated. Here, we report that RelB−/− mice develop age-related increased trabecular bone mass associated with increased bone formation. RelB−/− bone marrow stromal cells expanded faster in vitro and have enhanced OB differentiation associated with increased expression of the osteoblastogenic transcription factor, Runt-related transcription factor 2 (Runx2). In addition, RelB directly targeted the Runx2 promoter to inhibit its activation. Importantly, RelB−/− bone-derived MPCs formed bone more rapidly than wild-type cells after they were injected into a murine tibial bone defect model. Our findings indicate that RelB negatively regulates bone mass as mice age and limits bone formation in healing bone defects, suggesting that inhibition of RelB could reduce age-related bone loss and enhance bone repair. © 2014 American Society for Bone and Mineral Research.
Calcific Periarthritis as the Only Clinical Manifestation of Hypophosphatasia in Middle-Aged Sisters
Authors: Guañabens Núria , Mumm Steven , Möller Ingrid , González-Roca Eva , Peris Pilar , Demertzis Jennifer L , Whyte Michael P 
Published: October 2013

ABSTRACT

Hypophosphatasia (HPP) is the inborn error of metabolism that features low serum alkaline phosphatase (ALP) activity caused by loss-of-function mutation(s) within the gene for the tissue nonspecific isoenzyme of ALP (TNSALP). In HPP, extracellular accumulation of inorganic pyrophosphate (PPi), a TNSALP substrate and inhibitor of mineralization, leads frequently to premature tooth loss and often to rickets or osteomalacia. In affected adults, the excess PPi sometimes also causes calcium pyrophosphate dihydrate (CPPD) deposition, PPi arthropathy, or pseudogout, or seemingly paradoxical deposition of hydroxyapatite crystals in ligaments or around joints when the condition is called calcific periarthritis (CP). We report three middle-aged sisters with CP as the only clinical manifestation of HPP. Each presented during early adult life with recurrent episodes of pain principally around the shoulders, elbows, wrists, hips, or Achilles tendon. Otherwise, they were in good health, including no history of unusual dental disease, fractures, or pseudofractures. Calcific deposits were identified in symptomatic areas principally by ultrasonographic assessment but also confirmed radiographically. All three sisters had low serum levels of total and bone-specific ALP, hyperphosphatemia, and increased serum concentrations of the TNSALP substrate pyridoxal 5′-phosphate together characteristic of HPP. Mutation analysis revealed that each carried a single unique 18-bp duplication within TNSALP (c.188_205dup18, p.Gly63_Thr68dup) as did two of their healthy sons and their mother, who was without signs of CPPD deposition or CP but had knee osteoarthritis. We find that CP can be the only complication of HPP in adults. Thus, multiple juxta-articular deposits of hydroxyapatite causing CP may be a useful sign of HPP, especially when the CP is familial. © 2014 American Society for Bone and Mineral Research.
Raf Kinase Inhibitory Protein Role in the Molecular Subtyping of Breast Cancer
Authors: Al‐Mulla Fahd , Marafie Makia , Zea Tan Tuan , Paul Thiery Jean 
Published: October 2013

ABSTRACTIn this study, we examined the association between the RKIP expression and the molecular subtypes of breast cancer. Microarray gene expression data of 2,333 human breast cancer from 26 different cohorts performed on Affymetrix U133A or U133Plus2 platforms were downloaded from Array Express and Gene Expression Omnibus and the molecular subtype of breast cancer for the samples was determined by single sample Gene Set Enrichment Analysis. Differences in recurrence‐free survival (RFS) were tested using the Log‐rank test in univariate analysis and displayed using Kaplan–Meier curves. Cox proportional‐hazards model was used to calculate the hazard ratio using univariate and multivariate analysis. Loss or reduced RKIP expression was associated with reduced RFS in breast cancer using univariate and multivariate analyses, which was independent of lymph node (LN) metastasis status. Basal‐like, Claudin‐low, and Her‐2‐enriched tumors had significantly lower RKIP levels compared to other subclasses (P < 0.0001). Conversely, the Luminal subclass exhibited the highest expression levels of RKIP (P < 0.0001 for Luminal A and P = 0.0005 for Luminal B subtype), while in normal‐like breast cancer subtype, RKIP expression was not informative. RKIP expression was prognostic in ER+ and ER− subgroups. RKIP expression had no significant prognostic power within Basal‐like, Claudine‐low, Luminal B, or Her‐2‐enriched breast cancer subtypes. However, its expression pinpointed excellent from intermediate‐poor Luminal A survivors, in both ER+ (P = 0.035) and ER− (P = 0.012) subgroups, especially in LN negative breast cancers. In conclusion, RKIP expression adds significant value to the molecular subclassification of breast cancer especially for the Luminal A subtype. J. Cell. Biochem. 115: 488–497, 2014. © 2013 Wiley Periodicals, Inc.
Translation Regulation and Proteasome Mediated Degradation Cooperate to Keep Stem‐Loop Binding Protein Low in G1‐Phase
Authors: Djakbarova Umidahan , Marzluff William F. , Köseoğlu M. Murat 
Published: October 2013

ABSTRACTHistone mRNA levels are cell cycle regulated, and the major regulatory steps are at the posttranscriptional level. A major regulatory mechanism is S‐phase restriction of Stem‐loop binding protein (SLBP) which binds to the 3′ end of histone mRNA and participates in multiple steps of histone mRNA metabolism, including 3′ end processing, translation and regulation of mRNA stability. SLBP expression is cell cycle regulated without significant change in its mRNA level. SLBP expression is low in G1 until just before S phase where it functions and at the end of S phase SLBP is degraded by proteasome complex depending on phosphorylations on Thr60 and Thr61. Here using synchronized HeLa cells we showed that SLBP production rate is low in early G1 and recovers back to S phase level somewhere between early and mid‐G1. Further, we showed that SLBP is unstable in G1 due to proteasome mediated degradation as a novel mechanism to keep SLBP low in G1. Finally, the S/G2 stable mutant form of SLBP is degraded by proteasome in G1, indicating that indicating that the SLBP degradation in G1 is independent of the previously identified SLBP degradation at S/G2. In conclusion, as a mechanism to limit histone production to S phase, SLBP is kept low in G1 phase due to cooperative action of translation regulation and proteasome mediated degradation which is independent of previously known S/G2 degradation. J. Cell. Biochem. 115: 523–530, 2014. © 2013 Wiley Periodicals, Inc.
miRNA27a Is a Biomarker for Predicting Chemosensitivity and Prognosis in Metastatic or Recurrent Gastric Cancer
Authors: Huang Dingzhi , Wang Haiyan , Liu Rui , Li Hongli , Ge Shaohua , Bai Ming , Deng Ting , Yao Guangyu , Ba Yi 
Published: October 2013

AbstractWe previously identified five miRNAs (miR‐1, miR‐20a, miR‐27a, miR‐34a, and miR‐423‐5p) that are up‐regulated in gastric cancer. The goal of this study was to investigate the value of these miRNAs as potential biomarkers for predicting chemosensitivity and prognosis in metastatic or recurrent gastric cancer patients who received first‐line chemotherapy. A total of 82 patients with metastatic or recurrent GC receiving first‐line chemotherapy were included in our study. The expression levels of the five miRNAs were evaluated using hydrolysis probe‐based stem‐loop quantitative reverse transcription polymerase chain reaction (qRT‐PCR) in individual samples before first‐line chemotherapy. Patients receiving first‐line chemotherapy with fluoropyrimidine combined with oxaliplatin or paclitaxel were chosen for the chemosensitivity analysis. The relationships between expression of the five‐miRNAs and clinicopathological parameters, response to chemotherapy and prognosis were analyzed statistically. Patients with higher miRNA1 expression levels tended to have a higher rate of liver metastasis, and higher miRNA34a expression levels occurred more frequently in males (P = 0.022). The expression of the remaining three miRNAs showed no obvious relationship to any of the clinicopathological features. The partial response rates of the patients with high miRNA1 expression and low miRNA1 expression were 11.1% and 23.1%, respectively (P = 0.048). Similar results were observed for miRNA27a (the partial response rate was 7.7% vs. 25.9%, P = 0.018). Patients with up‐regulated miRNA27a expression had a significantly worse overall survival (OS) than patients with lower miRNA27a expression (P = 0.024). In patients with MRGC, miRNA27a is a potential biomarker for predicting resistance to fluoropyrimidine‐based chemotherapy and a novel prognostic marker for gastric cancer. J. Cell. Biochem. 115: 549–556, 2014. © 2013 Wiley Periodicals, Inc.
Review on the Recent Progress in Low Band Gap Conjugated Polymers for Bulk Hetero‐junction Polymer Solar Cells
Authors: Jhuo Hong‐Jyun , Yeh Po‐Nan , Liao Sih‐Hao , Li Yi‐Lun , Cheng Yu‐Shan , Chen Show‐An 
Published: October 2013

AbstractIn the past few years, tremendous progress in power conversion efficiency (PCE) of polymer solar cell (PSC) via design of novel conjugated polymers has been made. In order to further promote PCE, an efficient way is to narrow down optical band gap of the polymers. This review focuses on low band gap polymers based on Donor—Acceptor (D—A) strategy and quinoid form structure. At first, we introduce the requirements for polymers, such as tuning of energy levels. Second, we introduce the importance of main chain, side chain and substituents, which affect the optical and electrical properties, intra/intermolecular interactions, and charge mobility. We survey the important donor and acceptor units and discuss the guidelines for developing highly efficient conjugated polymers. We classify the polymers into several categories in accordance with the structures of acceptor units: Benzodiathiazole (BT), Thienopyrrolodione (TPD) and Diketopyrrolopyrrole (DPP), to which the copolymers with various donors have promissing efficiency. Low band gap polymers based on the quinoid structure, thienothiophene (TT), having promising efficiency are also included.
A drug and disease model for lixisenatide, a GLP‐1 receptor agonist in type 2 diabetes
Authors: Wilkins Justin J. , Dubar Michel , Sébastien Bernard , Laveille Christian 
Published: October 2013

AbstractIncretin hormone analogs such as glucagon‐like peptide‐1 (GLP‐1) receptor agonists have emerged as promising new options for the treatment of type 2 diabetes mellitus (T2DM), targeting several of its pathophysiological traits, including reduced insulin sensitivity, inadequate insulin secretion, and loss of β‐cell mass (BCM). This article describes the semi‐mechanistic modeling of lixisenatide dose‐response over time using fasting plasma glucose (FPG), fasting serum insulin (FSI) and glycated hemoglobin (HbA1c) data from two Phase II and four Phase III clinical trials, for a total of 2470 T2DM patients. Previously published models for FPG, FSI, and BCM as well as HbA1c were adapted and expanded to describe the available data. The model incorporated aspects describing disease progression, standard‐of‐care, FPG‐dependent and ‐independent HbA1c synthesis, and covariate effects of body size, race, and sex. The final model described lixisenatide effects on β‐cell responsiveness, insulin sensitivity and FPG‐independent HbA1c synthesis, was able to describe the observed FPG, FSI, and HbA1c data accurately, and was successful in predicting data from an unseen Phase III clinical study.
Pharmacokinetics of the novel dual endothelin receptor antagonist macitentan in subjects with hepatic or renal impairment
Authors: Sidharta Patricia N. , Lindegger Nicolas , Ulč Ivan , Dingemanse Jasper 
Published: October 2013

AbstractMacitentan is under development for the treatment of pulmonary arterial hypertension (PAH). Patients with PAH may suffer from comorbidities such as renal or hepatic impairment. Two prospective, single‐center, open‐label studies evaluated the pharmacokinetics of macitentan and its metabolites (pharmacologically active ACT‐132577 and inactive ACT‐373898) in healthy subjects and in subjects with mild, moderate, and severe hepatic impairment or severe renal function impairment (SRFI). After administering a single oral dose of 10 mg macitentan the pharmacokinetic parameters including area under the curve from zero to infinity (AUC∞) were derived from plasma concentration–time profiles. Exposure to macitentan and ACT‐132577 was lower in hepatically impaired versus healthy subjects, with no correlation with the degree of hepatic impairment. Exposure to ACT‐373898 was lower in subjects with moderate hepatic impairment only. Plasma concentration–time profiles for macitentan and ACT‐132577 (active) were similar in healthy subjects and subjects with SRFI. AUC∞ of ACT‐373898 (inactive) was 7.3‐fold higher in subjects with SRFI versus healthy subjects. No safety concerns were raised in either study. Based on these observations, pharmacokinetic alterations of macitentan due to hepatic or renal function impairment are not considered clinically relevant and no dose adjustment is necessary in these patients.