bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ubiquitin-specific protease 28 is overexpressed in human glioblastomas and contributes to glioma tumorigenicity by regulating MYC expression
Authors: Wang Zengwu , Song Qimin , Xue Jian , Zhao Yumei , Qin Shiqiang 
Published: July 2015

The transcription factor MYC, which is dysregulated in the majority of gliomas, is difficult to target directly. Deubiquitinase ubiquitin-specific protease 28 (USP28) stabilizes oncogenic factors, including MYC. However, the contribution of USP28 in tumorigenesis, particularly in glioma, is unknown. Here, we determined the expression of USP28 and assessed its clinical significance in human glioma. We found that USP28 is overexpressed in human glioma but not in normal brain tissue. The level of USP28 protein expression in human glioma tissues was directly correlated with glioma grade. Meanwhile, the level of USP28 protein expression in human glioblastoma tissues was inversely correlated with patient survival. Enforced USP28 expression promotes SW1783 glioma cell proliferation. Moreover, gliomas that arose from USP28-transfected SW1783 cells displayed tumorigenicity in nude mouse model systems. Inhibition of USP28 expression in glioblastoma U373 cells suppressed anchorage-independent growth in vitro and tumorigenicity in vivo. Furthermore, USP28 regulates the expression of MYC protein, which is essential in USP28-induced cell growth in glioma cells. These results showed that USP28 is overexpressed in human glioblastomas and it contributes to glioma tumorigenicity. Therefore, USP28 could be a new target of therapy for human malignant glioma.
Osteochondral Biopsy Analysis Demonstrates That BST-CarGel Treatment Improves Structural and Cellular Characteristics of Cartilage Repair Tissue Compared With Microfracture
Authors: Méthot Stéphane , Changoor Adele , Tran-Khanh Nicolas , Hoemann Caroline D. , Stanish William D. , Restrepo Alberto , Shive Matthew S. , Buschmann Michael D. 
Published: July 2015

Objective The efficacy and safety of BST-CarGel, a chitosan-based medical device for cartilage repair, was compared with microfracture alone at 1 year during a multicenter randomized controlled trial (RCT) in the knee. The quality of repair tissue of osteochondral biopsies collected from a subset of patients was compared using blinded histological assessments. Methods The international RCT evaluated repair tissue quantity and quality by 3-dimensional quantitative magnetic resonance imaging as co-primary endpoints at 12 months. At an average of 13 months posttreatment, 21/41 BST-CarGel and 17/39 microfracture patients underwent elective second look arthroscopies as a tertiary endpoint, during which ICRS (International Cartilage Repair Society) macroscopic scoring was carried out, and osteochondral biopsies were collected. Stained histological sections were evaluated by blinded readers using ICRS I and II histological scoring systems. Collagen organization was evaluated using a polarized light microscopy score. Results BST-CarGel treatment resulted in significantly better ICRS macroscopic scores ( P = 0.0002) compared with microfracture alone, indicating better filling, integration, and tissue appearance. Histologically, BST-CarGel resulted in a significant improvement of structural parameters— Surface Architecture ( P = 0.007) and Surface/Superficial Assessment ( P = 0.042)—as well as cellular parameters— Cell Viability ( P = 0.006) and Cell Distribution ( P = 0.032). No histological parameters were significantly better for the microfracture group. BST-CarGel treatment also resulted in a more organized repair tissue with collagen stratification more similar to native hyaline cartilage, as measured by polarized light microscopy scoring ( P = 0.0003). Conclusion Multiple and independent analyses in this biopsy substudy demonstrated that BST-CarGel treatment results in improved structural and cellular characteristics of repair tissue at 1 year posttreatment compared with microfracture alone, supporting previously reported results by quantitative magnetic resonance imaging.
Depth-Dependent Glycosaminoglycan Concentration in Articular Cartilage by Quantitative Contrast-Enhanced Micro–Computed Tomography
Authors: Mittelstaedt Daniel , Xia Yang 
Published: July 2015

Objective A quantitative contrast-enhanced micro–computed tomography (qCECT) method was developed to investigate the depth dependency and heterogeneity of the glycosaminoglycan (GAG) concentration of ex vivo cartilage equilibrated with an anionic radiographic contrast agent, Hexabrix. Design Full-thickness fresh native ( n = 19 in 3 subgroups) and trypsin-degraded ( n = 6) articular cartilage blocks were imaged using micro–computed tomography (μCT) at high resolution (13.4 μm3) before and after equilibration with various Hexabrix bathing concentrations. The GAG concentration was calculated depth-dependently based on Gibbs-Donnan equilibrium theory. Analysis of variance with Tukey’s post hoc was used to test for statistical significance ( P < 0.05) for effect of Hexabrix bathing concentration, and for differences in bulk and zonal GAG concentrations individually and compared between native and trypsin-degraded cartilage. Results The bulk GAG concentration was calculated to be 74.44 ± 6.09 and 11.99 ± 4.24 mg/mL for native and degraded cartilage, respectively. A statistical difference was demonstrated for bulk and zonal GAG between native and degraded cartilage ( P < 0.032). A statistical difference was not demonstrated for bulk GAG when comparing Hexabrix bathing concentrations ( P > 0.3214) for neither native nor degraded cartilage. Depth-dependent GAG analysis of native cartilage revealed a statistical difference only in the radial zone between 30% and 50% Hexabrix bathing concentrations. Conclusions This nondestructive qCECT methodology calculated the depth-dependent GAG concentration for both native and trypsin-degraded cartilage at high spatial resolution. qCECT allows for more detailed understanding of the topography and depth dependency, which could help diagnose health, degradation, and repair of native and contrived cartilage.
Acute embolic occlusion of the right common iliac artery after revision total hip arthroplasty treated with catheter-directed thrombolysis and balloon angioplasty: A case report
Authors: Yang Hongqi , Lei Qing , Chen Song , Chen Li , Li Yuefeng , Chai Yasheng , Wei Ping , Xu Shunchi , Liu Tangyou , Liu Feng , Zhang Zhuo 
Published: July 2015

Methods: A 63-year-old woman with atrial fibrillation presented clinical symptoms and signs of acute ischemia in the right lower extremity on the 17th postoperative day after revision total hip arthroplasty of the left hip for aseptic loosening of femoral component. Aspirin was discontinued 7 days before surgery. Both computed tomography angiography and digital subtraction angiography demonstrated complete occlusion of the right common iliac artery. An emergency catheter-directed thrombolysis with urokinase combined with balloon angioplasty was performed to obtain complete patency of the right common iliac artery. Results: The patient received anticoagulation and antiplatelet therapy postoperatively and was fine at the 2-year follow-up. Conclusions: This case demonstrated that catheter-directed thrombolysis combined with balloon angioplasty could be an efficacious, minimally invasive approach for the treatment of acute embolic occlusion of the common iliac artery. Preoperative anticoagulation for patients undergoing total hip arthroplasty with long-term use of aspirin for atrial fibrillation needs further investigation.
Type 1 serrated polyposis represents a predominantly female disease with a high prevalence of dysplastic serrated adenomas, without germline mutation in MUTYH, APC, and PTEN genes
Authors: Petronio Marco , Pinson Stephane , Walter Thomas , Joly Marie‐Odile , Hervieu Valerie , Forestier Julien , Saurin Jean‐Christophe 
Published: July 2015

AimThe aim of this article is to clarify the epidemiologic, clinical, endoscopic, biological and genetic characteristics of type 1 serrated polyposis patients.Patients and methodsConsecutive patients responding to the WHO definition of type 1 serrated polyposis in one reference center for polyposis patients accepted genetic counseling. Detailed data on previous endoscopies, histology, and life habits were recorded, after informed consent, germline analysis of MUTYH, APC, and PTEN germline mutations. Molecular biology was tested on available fixed tissue from different lesion types.ResultsWe included 29 patients (mean age 53.5 years, 21 women (72.4%)), four with a personal history of colorectal cancer (CRC), with a mean of 11.6 SSAs, with associated hyperplastic polyps in 93.1% and adenomas in 82.8%. SSAs showed no dysplasia in 46.9% of lesions (three of 29 patients), LGD in 51.9% (22/29 patients), and HGD in 1.2% (four of 29 patients). Dysplasia was more frequent in proximal SSAs and in women. Colectomy 15 patients (51.7%), upper digestive neoplasms: eight patients (27.5%); smokers: 24 patients (82.8%); family history of CRC: 16 patients (55.2%). Biology: MSI‐H phenotype in one SSA, V600E BRAF mutation in 95% of SSAs; MGMT hypermethylation in three of 17 SSAs. No germline mutation was detected in MYH, APC or PTEN genes.ConclusionType 1 serrated polyposis corresponds to a majority of women, with a high prevalence of smokers, a high prevalence of dysplastic serrated adenomas, particularly in females, without identified germline mutation in targeted predisposing genes.
Prevalence of severe esophagitis in Spain. Results of the PRESS study (Prevalence and Risk factors for Esophagitis in Spain: A cross‐sectional study)
Authors: Piqué Núria , Ponce Marta , Garrigues Vicente , Rodrigo Luis , Calvo Félix , de Argila Carlos Martín , Borda Fernando , Naranjo Antonio , Alcedo Javier , José Soria María , Rey Enrique , Bujanda Luis , Gisbert Javier P , Suarez David , Calvet Xavier , Ponce Julio ,   PRESS Study Group
Published: July 2015

BackgroundThe current prevalence of esophagitis in southern Europe is unknown. In addition, the risk factors for reflux esophagitis are not fully understood.ObjectiveThe objective of this article is to assess the prevalence and risk factors for esophagitis in Spain.MethodsA prospective, observational, cross‐sectional, multicenter study (PRESS study) was conducted among 31 gastrointestinal endoscopy units throughout Spain. A total of 1361 patients undergoing upper gastrointestinal endoscopy were enrolled. Sociodemographic, clinical and treatment data were recorded.ResultsA total of 95% of patients were Caucasian and 52% were male (mean age: 53 ± 17 years). The most frequent symptoms prompting endoscopy were heartburn (40%), regurgitation (26%) and dysphagia (15%). Fifty‐four percent of patients undergoing endoscopy were receiving proton pump inhibitor (PPI) treatment. Esophagitis (mainly mild‐moderate) was present in 154 (12.4%) patients. The severe form was recorded in only 11 (0.8%) patients. Multivariate analysis results indicated that the likelihood of esophagitis was higher in men (OR = 1.91, 95% CI = 1.31–2.78), in patients with high GERD‐Q scores (OR = 1.256, 95% CI = 1.176–1.343), weight increase (OR = 1.014, 95% CI = 1.003–1.025) and high alcohol consumption (OR = 2.49, 95% CI = 1.16–5.36).ConclusionSevere esophagitis is a rare finding in the Spanish population. Male gender, high GERD‐Q score, weight increase and high alcohol consumption are main risk factors for its appearance.
Nickel sensitization in patients with gastro‐esophageal reflux disease
Authors: Stanghellini Vincenzo , Tosetti Cesare , Benedetto Edoardo , Condoluci Mario , De Bastiani Rudi , Cogliandro Rosanna , Mastronuzzi Tecla , De Polo Manuela , Di Mita Francesco , Napoli Luigi , Ubaldi Enzo , Nebiacolombo Cristina , Cottone Carmelo , Grattagliano Ignazio , Zamparella Maria , Baldi Elisabetta , Sanna Guido 
Published: July 2015

BackgroundGastro‐esophageal reflux disease (GERD) leads to frequent medical visits, and available therapies fail in up to 40% of patients. Food allergies may be involved in GERD pathogenesis; however, allergens other than food have received little attention. Nickel allergy is common in the general population and some high‐nickel foods are associated with GERD. However, the potential relationship between nickel allergy and GERD remains unaddressed.AimThis study aimed to evaluate the prevalence of nickel sensitization in patients with and without GERD and to compare clinical and demographic features.MethodsThis prospective, multicenter study included 210 adult GERD patients and 140 patients without GERD who presented at the general practitioner. All GERD patients had undergone treatment with proton pump inhibitors and upper digestive endoscopy within the previous five years. Demographic and clinical data were collected by questionnaire and patients underwent a nickel patch allergy test.ResultsPatients with and without GERD presented similar characteristics, with the exception of nickel sensitization, which was significantly more prevalent among GERD patients than controls (39.5% vs. 16.4%; p  = 0.001). Nickel‐positive GERD patients were more frequently female (90.4% vs. 65.4%, p  = 0.003) and asthmatic (18.1% vs. 4.7%; p  = 0.038), compared to nickel‐negative GERD patients. At six‐month follow‐up, most of the patients, with or without nickel sensitization, reported improved symptoms without differences in drug prescription.ConclusionNickel sensitization is particularly prevalent in GERD patients seen in general practice. Whether allergies other than food allergy play a role in GERD remains to be elucidated.
In vitro fertilization‐induced pregnancies predispose to gastroesophageal reflux disease
Authors: Turan Ilker , Kitapcioglu Gul , Tavmergen Goker Ege , Sahin Gulnaz , Bor Serhat ,   Ege Reflux Study Group
Published: July 2015

BackgroundWomen conceiving following in vitro fertilization (IVF) likely have a variety of risk factors that predispose them to gastroesophageal reflux disease (GERD) in the future.ObjectiveWe aimed to investigate whether pregnancy through IVF may predispose to subsequent GERD compared with pregnancies without IVF. We also evaluate whether twin IVF pregnancies lead to additional risk for having GERD compared with singleton IVF pregnancies.MethodsA validated reflux questionnaire was administered to 156 women with singleton (n  = 102) or twin (n  = 54) IVF birth (IVF group) and 111 women with a naturally conceived singleton birth (control group). All women included in the study were primiparas who had given birth at least 1 year prior to data collection. The diagnosis of GERD was based on the occurrence of typical symptoms (heartburn, regurgitation, or both) at least once a week.ResultsThe prevalence of GERD was 13.5% and 4.5% in IVF and control groups (p  = 0.015); in the IVF group, this was slightly higher, but not statistically significant, in women with twin compared with singleton pregnancies (14.8% vs. 12.7%, p  = 0.749). Logistic regression analysis showed that IVF was strongly associated with subsequent GERD (OR, 3.30; 95% CI 1.20–9.04; p  = 0.02).ConclusionThe risk of developing GERD at least 1 year after delivery increased following IVF. Long‐term follow‐up studies are required to determine whether therapy during pregnancy can prevent this risk.
Influence of reflux and central obesity on intercellular space diameter of esophageal squamous epithelium
Authors: Blevins Christopher H , Sharma Anamay N , Johnson Michele L , Geno Deborah , Gupta Milli , Bharucha Adil E , Katzka David A , Iyer Prasad G 
Published: July 2015

BackgroundWhile central obesity increases gastroesophageal reflux (GER) by mechanically disrupting the anti‐reflux barrier, limited data exist on pathways by which central obesity may potentiate esophageal injury by non‐mechanical means. Obesity has been associated with an impaired epithelial intestinal barrier.ObjectiveWe aimed to assess the influence of central obesity and reflux on the squamous esophageal epithelial intercellular space diameter (ICSD).MethodsThe ICSD was measured using electron microscopy in esophageal biopsies from individuals who underwent ambulatory pH monitoring and endoscopy. Anthropometric measurements were obtained on all participants. Participants were classified into four groups: with and without central obesity and reflux.ResultsSixteen individuals were studied with four in each study group. The mean ICSD was almost three‐fold greater (p  < 0.001) in the group with central obesity without reflux, compared to controls without central obesity and reflux. It was also comparable to the ICSD in groups with acid reflux only and those with both reflux and central obesity.ConclusionsThere is evidence of esophageal squamous ICSD increase in individuals with central obesity who do not have evidence of acid and nonacid reflux on ambulatory pH monitoring. This may reflect a mechanism by which central obesity potentiates reflux‐induced esophageal injury and inflammation.
Heterogeneity of sickness absence and disability pension trajectories among individuals with MS
Authors: Björkenstam Charlotte , Alexanderson Kristina , Wiberg Michael , Hillert Jan , Tinghög Petter 
Published: July 2015

Background The variability of progression of multiple sclerosis (MS) suggests that MS is a heterogeneous entity. Objective The objective of this article is to determine whether sickness absence (SA) and disability pension (DP) could be used to identify groups of patients with different progression courses. Methods We analyzed mean-annual net months of SA/DP, five years prior to MS diagnosis, until the year of diagnosis, and five years after for 3543 individuals diagnosed 2003–2006, by modeling trajectory subgroups. Results Five different groups were identified, revealing substantial heterogeneity among MS patients. Before diagnosis, 74% had a flat trajectory, while the remaining had a sharply increasing degree of SA/DP. After diagnosis, 95% had a flat or marginally increasing trajectory, although at various SA/disability pension (DP) levels, whereas a small group of 5% had decreasing SA/DP. A majority had few or no SA/DP months throughout the 11-year study period. Higher age and a lower educational level were associated with an unfavorable trajectory ( p values <0.01). Conclusions There’s a considerable heterogeneity of MS progression in terms of SA/DP. Compared with other measures of disability, sickness-absence and disability pension offer a continuous variable that can be assigned to every individual for each time period without missing data. To what extent the SA/DP measure reflects classical MS outcome-measures as well as how correlated it is with co-morbidities and working-conditions needs to be investigated further.
Association of plasma levels of Protein S with disease severity in multiple sclerosis
Authors: Ma Gerry ZM , Giuffrida Lauren L , Gresle Melissa M , Haartsen Jodi , Laverick Louise , Butzkueven Helmut , Field Judith , Binder Michele D , Kilpatrick Trevor J 
Published: July 2015

Background The TAM family of receptor tyrosine kinases (TYRO3, AXL and MERTK) play important roles in modulating innate immune responses and central demyelination. The TAM receptor ligand Protein S (PROS) has also been shown to modulate innate immune cell responses. Objectives We assessed whether plasma levels of PROS are changed in multiple sclerosis (MS) patients and whether changes are associated with disease severity. Methods Plasma levels of total and free PROS were measured using enzyme-linked immunosorbent assay in a discovery cohort (MS: 65, control: 14) and an independent replication cohort (MS: 29, control: 29). The Multiple Sclerosis Severity Score (MSSS) was used to evaluate associations between plasma PROS levels and disease severity. Results We found plasma levels of total, but not free PROS, were decreased in MS patients compared with controls. In female MS patients, we observed decreases in total and free PROS levels compared with controls. In addition, we also observed higher MSSS in patients with very low levels of plasma free PROS. Conclusions These data suggest PROS may represent a potential marker of disease severity in MS.
Suppression of in vitro megakaryopoiesis by maternal sera containing anti-HPA-1a antibodies
Authors: Liu Zhi-Jian , Bussel James B. , Lakkaraja Madhavi , Ferrer-Marin Francisca , Ghevaert Cedric , Feldman Henry A. , McFarland Janice G. , Chavda Chaitanya , Sola-Visner Martha 
Published: July 2015

Key Points
Maternal sera containing anti-HPA-1a antibodies suppress in vitro megakaryopoiesis through induction of cell death. The degree of suppression of megakaryopoiesis is variable and is one of the factors determining the severity of neonatal thrombocytopenia.
Platelet-derived VWF is not essential for normal thrombosis and hemostasis but fosters ischemic stroke injury in mice
Authors: Verhenne Sebastien , Denorme Frederik , Libbrecht Sarah , Vandenbulcke Aline , Pareyn Inge , Deckmyn Hans , Lambrecht Antoon , Nieswandt Bernhard , Kleinschnitz Christoph , Vanhoorelbeke Karen , De Meyer Simon F. 
Published: July 2015

Key Points
Platelet-derived VWF alone mediates full ischemic stroke injury in mice via a GPIb-dependent mechanism. Platelet-derived VWF does not significantly contribute to normal thrombosis and hemostasis in mice.
Zebrafish adult-derived hypothalamic neurospheres generate gonadotropin-releasing hormone (GnRH) neurons
Authors: Cortés-Campos Christian , Letelier Joaquín , Ceriani Ricardo , Whitlock Kathleen E. 
Published: July 2015

ABSTRACTGonadotropin-releasing hormone (GnRH) is a hypothalamic decapeptide essential for fertility in vertebrates. Human male patients lacking GnRH and treated with hormone therapy can remain fertile after cessation of treatment suggesting that new GnRH neurons can be generated during adult life. We used zebrafish to investigate the neurogenic potential of the adult hypothalamus. Previously we have characterized the development of GnRH cells in the zebrafish linking genetic pathways to the differentiation of neuromodulatory and endocrine GnRH cells in specific regions of the brain. Here, we developed a new method to obtain neural progenitors from the adult hypothalamus in vitro. Using this system, we show that neurospheres derived from the adult hypothalamus can be maintained in culture and subsequently differentiate glia and neurons. Importantly, the adult derived progenitors differentiate into neurons containing GnRH and the number of cells is increased through exposure to either testosterone or GnRH, hormones used in therapeutic treatment in humans. Finally, we show in vivo that a neurogenic niche in the hypothalamus contains GnRH positive neurons. Thus, we demonstrated for the first time that neurospheres can be derived from the hypothalamus of the adult zebrafish and that these neural progenitors are capable of producing GnRH containing neurons.