bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scoping systematic review on the extent, nature and quality of evidence underlying ophthalmic and paraophthalmic education
Authors: Williams Michael , Boohan Mairead , Thurston Allen 
Published: December 2016

BackgroundEffective education of relevant professionals underpins provision of quality eye healthcare.ObjectivesThis scoping systematic review had 2 aims: first to investigate the extent and nature of scholarly output published on ophthalmic and paraophthalmic education, and second to focus on the quality of reporting of randomised controlled trials (RCTs) identified.Study selectionA search strategy was created and applied to PubMed. Any scholarly publications on any aspect of education of those involved in the care of patients with visual problems as the main theme or context was selected. Predefined data were extracted.FindingsOf 255 studies included, the most common type of scholarly publications were descriptions of an educational innovation, opinion pieces and descriptive studies. RCTs made up 5.5% of the sample. Most of the 14 RCTs failed to report most of the items recommended in the CONSORT guidelines.ConclusionsThis review highlights the need for investigators, ethical committees and journals to insist on a better quality of RCT conduct than is presently apparent, but also that clinicians should not be blind to the strengths of non-RCT-based studies in the field of education.
A randomised experiment comparing low-cost ultrasound gel alternative with commercial gel
Authors: Riguzzi Christine , Binkowski Allison , Butterfield Mike , Sani Farhad , Teismann Nathan , Fahimi Jahan 
Published: December 2016

ObjectivePoint-of-care ultrasound is a portable, relatively low-cost imaging modality with great potential utility in low-resource settings. However, commercially produced ultrasound gel is often cost-prohibitive and unavailable. We investigated whether images obtained using an alternative cornstarch-based gel would be of comparable quality with those using commercial gel.MethodsThis was a blinded, randomised, cross-over study comparing commercially produced ultrasound gel with home-made cornstarch-based gel. Ultrasound-trained faculty obtained three video clips with each gel type from patients at one urban ED. The clips were evaluated by a radiologist and an ultrasound-trained emergency physician. Images were assessed in terms of overall adequacy (dichotomous) and quality, resolution and detail using a rating scale (0–10). All sonographers and physicians reviewing the images were blinded to the type of gel used.ResultsThirty-four patients were enrolled in the study, producing 204 separate images (102 with each gel). The cornstarch gel clips were deemed accurate in 70.6% (95% CI 63.9% to 76.5%) of the scans, as compared with 65.2% (95% CI 58.4% to 71.4%) of those using commercial gel. There was no difference between the two groups with respect to image detail, resolution or quality.ConclusionsImages produced using the cornstarch-based alternative ultrasound gel were of similar quality to those using commercial gel. The low cost and easy preparation of the cornstarch-based gel make it an attractive coupling medium for use in low-resource settings.
Adipose type I interferon signalling protects against metabolic dysfunction
Authors: Wieser Verena , Adolph Timon Erik , Grander Christoph , Grabherr Felix , Enrich Barbara , Moser Patrizia , Moschen Alexander Rupert , Kaser Susanne , Tilg Herbert 
Published: December 2016

ObjectiveLow-grade chronic inflammation emerges as a potent driver of insulin resistance and glucose dysregulation in obesity and associated non-alcoholic fatty liver disease (NAFLD). The liver, subcutaneous fat and the immune system participate in disturbances of metabolism. Type I interferon (IFN) signalling initiated by innate and adaptive immunity modulates inflammatory responses consequent to infection. However, little is known about the role of type I IFN signalling in metabolic diseases and the development of NAFLD.DesignWe determined the impact of type I IFN signalling by tissue-specific deletion of interferon (α and β) receptor 1 (Ifnar1) in hepatocytes (Ifnar1Δhep), adipocytes (Ifnar1Δat), intestinal epithelial cells (Ifnar1ΔIEC) or myelocytes (Ifnar1Δmyel) on glucose metabolism, obesity and hepatic disease in mice exposed to a high-fat or methionine-choline-deficient (MCD) diet. Furthermore, we investigated the expression of type I IFN-regulated genes in patients with obesity undergoing laparoscopic adjustable gastric banding (LAGB).ResultsLong chain fatty acids induce type I IFN responses in murine hepatocytes and macrophages and exposure to a high-fat diet elicited type I IFN-regulated gene expression in the liver of wild-type mice. Hepatocyte-specific, but not adipose tissue-specific deletion of Ifnar1 worsened steatosis and inflammation induced by the MCD diet. In contrast, adipose-specific, but not hepatocyte-specific deletion of Ifnar1 deteriorated metabolic dysregulation induced by a high-fat diet, indicated by increased weight gain, insulin resistance and an impaired glucose tolerance. Abrogated type I IFN signalling in myeloid or intestinal epithelial cells did not modulate susceptibility to metabolic or hepatic disease. Improved metabolic control in patients with obesity after LAGB was associated with increased expression of type I IFN-regulated genes in subcutaneous adipose tissue and liver.ConclusionsOur study implicates a role for adipose and hepatocyte type I IFN signalling in diet-induced metabolic dysregulation and hepatic disease. Further studies on type I IFN signalling in metabolic diseases are warranted.
Anaplastic lymphoma kinase expression and gene alterations in glioblastoma: correlations with clinical outcome
Authors: Karagkounis George , Stranjalis George , Argyrakos Theodore , Pantelaion Varvara , Mastoris Konstantinos , Rontogianni Dimitra , Komaitis Spyridon , Kalamatianos Theodosis , Sakas Damianos , Tiniakos Dina 
Published: December 2016

AimsTo study anaplastic lymphoma kinase (ALK) protein expression and possible underlying gene alterations in glioblastoma (GBM), correlating them with clinical outcome.MethodsWe studied ALK immunohistochemical expression and fluorescent in situ hybridisation (FISH)-detected ALK gene alterations in 51 GBMs (46 isocitrate dehydrogenase-1 (IDH1)R132H-negative and 5 IDH-mutant (IDH1R132H-positive)). We compared two anti-ALK antibodies and immunohistochemical detection systems (5Α4/Nichirei Biosciences, D5F3/Ventana). The results were correlated with tumour cell proliferation and clinical outcome.ResultsIntense granular cytoplasmic ALK immunostaining was observed in 10/51 (19.61%) GBM and correlated with high Ki67 proliferation index; only 1 in 10 ALK-positive cases displayed multiplealkgene signals by FISH. Moderate ALK immunostaining was observed in 21 (41.17%), weak immunostaining in 5 (9.80%) while 15 (29.42%) cases were negative. p53 was expressed in 26/51 GBM (50.9%) (10% cut-off). IDH1R132H-negative GBM showed higher ALK expression compared with IDH-mutant GBM (65.2% vs 20%). ALK overexpression was more common in older patients but did not correlate with other clinicopathological variables or patient overall survival.ConclusionsALK overexpression can be identified in up to 70% of GBMs and does not correlate with underlyingalkgene amplification. Despite being more common in rapidly growing, clinically aggressive GBM, ALK overexpression did not show correlation with prognosis in this study.
Examining the potential use and long-term stability of guaiac faecal occult blood test cards for microbial DNA 16S rRNA sequencing
Authors: Taylor Morag , Wood Henry M , Halloran Stephen P , Quirke Philip 
Published: December 2016

AimsWith a growing interest in the influence the gut microbiome has on the development of colorectal cancer (CRC), we investigated the feasibility and stability of isolating and typing microbial DNA from guaiac faecal occult blood test (gFOBt) cards. This has the future potential to screen the microbial populations present in confirmed colorectal neoplasia cases with aims to predict the presence and development of CRC.MethodsFresh stool samples from three healthy volunteers were applied to gFOBt cards. DNA was extracted from both the cards and fresh stool samples. A series of additional cards were prepared from one volunteer, and extracted at time points between 2 weeks and 3 years. The V4 region of the 16S rRNA gene was amplified and sequenced on an Illumina MiSeq at 2×250 bp read lengths. Data were analysed using QIIME software.ResultsSamples were grouped both by volunteer and by type (fresh or gFOBt), and compared a variety of ways: visual inspection of taxa, α and β diversity, intraclass correlation. In all comparisons, samples grouped by volunteer, and not by sample type. The different time points showed no appreciable differences with increased storage time.ConclusionsThis study has demonstrated that there is good concordance between microbial DNA isolated from fresh stool sample, and from the matched gFOBt card. Samples stored for up to 3 years showed no detrimental effect on measureable microbial DNA. This study has important future implications for investigating microbial influence on CRC development and other pathologies.
Impact of contaminated household environment on stunting in children aged 12–59 months in Burkina Faso
Authors: Fregonese Federica , Siekmans Kendra , Kouanda Seni , Druetz Thomas , Ly Antarou , Diabaté Souleymane , Haddad Slim 
Published: December 2016

BackgroundStunting affects 165 million children worldwide, with repercussions on their survival and development. A contaminated environment is likely to contribute to stunting: frequent faecal-oral transmission possibly causes environmental enteropathy, a chronic inflammatory disorder that may contribute to faltering growth in children. This study's objective was to assess the effect of contaminated environment on stunting in Burkina Faso, where stunting prevalence is persistently high.MethodsPanel study of children aged 1–5 years in Kaya. Household socioeconomic characteristics, food needs and sanitary conditions were measured once, and child growth every year (2011–2014). Using multiple correspondence analysis and 12 questions and observations on water, sanitation, hygiene behaviours, yard cleanliness and animal proximity, we constructed a ‘contaminated environment’ index as a proxy of faecal-oral transmission exposure. Analysis was performed using a generalised structural equation model (SEM), adjusting for repeat observations and hierarchical data.ResultsStunting (<2 SD height-for-age) prevalence was 29% among 3121 children (median (IQR) age 36 (25–48) months). Environment contamination was widespread, particularly in rural and peri-urban areas, and was associated with stunting (prevalence ratio 1.30; p=0.008), controlling for sex, age, survey year, setting, mother's education, father's occupation, household food security and wealth. This association was significant for children of all ages (1–5 years) and settings. Lower contamination and higher food security had effects of comparable magnitude.ConclusionsEnvironment contamination can be at least as influential as nutritional components in the pathway to stunting. There is a rationale for including interventions to reduce environment contamination in stunting prevention programmes.
Latest generation of flat detector CT as a peri-interventional diagnostic tool: a comparative study with multidetector CT
Authors: Leyhe Johanna Rosemarie , Tsogkas Ioannis , Hesse Amélie Carolina , Behme Daniel , Schregel Katharina , Papageorgiou Ismini , Liman Jan , Knauth Michael , Psychogios Marios-Nikos 
Published: December 2016

Background and purposeFlat detector CT (FDCT) has been used as a peri-interventional diagnostic tool in numerous studies with mixed results regarding image quality and detection of intracranial lesions. We compared the diagnostic aspects of the latest generation FDCT with standard multidetector CT (MDCT).Materials and methods102 patients were included in our retrospective study. All patients had undergone interventional procedures. FDCT was acquired peri-interventionally and compared with postinterventional MDCT regarding depiction of ventricular/subarachnoidal spaces, detection of intracranial hemorrhage, and delineation of ischemic lesions using an ordinal scale. Ischemic lesions were quantified with the Alberta Stroke Program Early CT Scale (ASPECTS) on both examinations. Two neuroradiologists with varying grades of experience and a medical student scored the anonymized images separately, blinded to the clinical history.ResultsThe two methods were of equal diagnostic value regarding evaluation of the ventricular system and the subarachnoidal spaces. Subarachnoidal, intraventricular, and parenchymal hemorrhages were detected with a sensitivity of 95%, 97%, and 100% and specificity of 97%, 100%, and 99%, respectively, using FDCT. Gray–white differentiation was feasible in the majority of FDCT scans, and ischemic lesions were detected with a sensitivity of 71% on FDCT, compared with MDCT scans. The mean difference in ASPECTS values on FDCT and MDCT was 0.5 points (95% CI 0.12 to 0.88).ConclusionsThe latest generation of FDCT is a reliable and accurate tool for the detection of intracranial hemorrhage. Gray–white differentiation is feasible in the supratentorial region.
The crater lake of Copahue volcano (Argentina): geochemical and thermal changes between 1995 and 2015
Authors: Agusto Mariano R. , Caselli Alberto , Daga Romina , Varekamp Johan , Trinelli Alcira , Dos Santos Afonso María , Velez María Laura , Euillades Pablo , Ribeiro Guevara Sergio 
Published: December 2016

Abstract
The crater lake and associated hydrothermal features of Copahue volcano have been studied intensively over the last 20 years (1995–2015). The geochemical and isotopic compositions of the waters provide insights into the processes occurring in the volcanic–hydrothermal system, the crater lake and the thermal springs. Variations in the temperature and chemical composition of the waters reveal fundamental changes in the system that precede and accompany the magmatic and phreatic eruptive events at Copahue. A conceptual model of the summit system was developed involving the intrusion of slivers of magma in the hot acidic hydrothermal cell, the saturation of waters with secondary minerals leading to reduced permeability, the blocking of fluid pathways by liquid sulphur during heating events and the transport of gas from the magma through the ductile–brittle transition into the hydrothermal system. Geophysical data were integrated with the chemical data to provide new insights into the behaviour of the deep magmatic system that feeds the volcano edifice. Multidisciplinary studies were used to identify precursory signals of eruptive activity to give an early warning of pending volcanic hazards. Several geochemical ratios in river water were identified as potential indicators of upcoming volcanic activity, which could be used in co-operation with the community and local authorities to deal with these volcanic hazards.
Association of serum HMGB2 level with MACE at 1 mo of myocardial infarction: Aggravation of myocardial ischemic injury in rats by HMGB2 via ROS
Authors: Liu Zhu Hui , Dai Dao Peng , Ding Feng Hua , Pan Wen Qi , Fang Yue Hua , Zhang Qi , Li Man , Yang Ping , Wang Xiao Qun , Shen Ying , Wang Ling Jie , Yan Xiao Xiang , He Yu Hu , Yang Ke , Zhang Rui Yan , Shen Wei Feng , Chen Ying , Lu Lin 
Published: December 2016

High-mobility group box (HMGB) family is related to inflammatory diseases. We investigated whether serum HMGB2 levels are related to myocardial infarction (MI) severity and major adverse cardiac events (MACE) during MI. We included 432 consecutive patients with ST-segment elevation myocardial infarction and 312 controls. Serum HMGB2 levels were significantly higher in MI patients than in controls. Increased HMGB2 levels were associated with MACE and negatively with ejection fraction in MI patients. HMGB2 was an independent determinant of MACE in logistic regression analysis. HMGB2 protein (10 μg) or saline was injected intramyocardially in MI rats, with or without coadministration of the NADPH oxidase inhibitor apocynin. After 72 h, pathological, echocardiographic, and hemodynamic examinations showed that HMGB2 increased infarct size and worsened cardiac function in MI rats. Moreover, HMGB2 administration enhanced reactive oxygen species (ROS) production, cell apoptosis, inflammation, and autophagosome clearance impairment, which were attenuated by coadministration of apocynin or knock down of receptor for advanced glycation end products (RAGE). In conclusion, increased serum HMGB2 levels are associated with MI severity and MACE at 1 mo. HMGB2 promotes myocardial ischemic injury in rats and hypoxic H9C2 cell damage via ROS provoked by RAGE.NEW & NOTEWORTHY We demonstrate that serum high-mobility group box 2 is associated with major adverse cardiac events at 1 mo in myocardial infarction patients. Mechanistically, high-mobility group box 2 promotes reactive oxygen species production via receptor for advanced glycation end products signaling in ischemic myocardium, thereby aggravating cell apoptosis, inflammation, and autophagosome clearance impairment. This study reveals that high-mobility group box 2 is a novel factor enhancing ischemic injury in myocardial infarction.
Gastric Cancer Cell Proliferation and Survival Is Enabled by a Cyclophilin B/STAT3/miR-520d-5p Signaling Feedback Loop
Authors: Li Ting , Guo Hanqing , Zhao Xiaodi , Jin Jiang , Zhang Lifeng , Li Hong , Lu Yuanyuan , Nie Yongzhan , Wu Kaichun , Shi Yongquan , Fan Daiming 
Published: December 2016

Abstract
Molecular links between inflammation and cancer remain obscure despite their great pathogenic significance. The JAK2/STAT3 pathway activated by IL6 and other proinflammatory cytokines has garnered attention as a pivotal link in cancer pathogenesis, but the basis for its activation in cancer cells is not understood. Here we report that an IL6-triggered feedback loop involving STAT3-mediated suppression of miR-520d-5p and upregulation of its downstream target cyclophilin B (CypB) regulate the growth and survival of gastric cancer cells. In clinical specimens of gastric cancer, we documented increased expression of CypB and activation of STAT3. Mechanistic investigations identified miR-520d-5p as a regulator of CypB mRNA levels. This signaling axis regulated gastric cancer growth by modulating phosphorylation of STAT3. Furthermore, miR-520d-5p was identified as a direct STAT3 target and IL6-mediated inhibition of miR-520d-5p relied upon STAT3 activity. Our findings define a positive feedback loop that drives gastric carcinogenesis as influenced by H. pylori infections that involve proinflammatory IL6 stimulation. Cancer Res; 77(5); 1227–40. ©2016 AACR.
The Natural Diterpenoid Isoforretin A Inhibits Thioredoxin-1 and Triggers Potent ROS-Mediated Antitumor Effects
Authors: Sun Xiaoyan , Wang Weiguang , Chen Jiao , Cai Xueting , Yang Jie , Yang Yang , Yan Huaijiang , Cheng Xiaolan , Ye Juan , Lu Wuguang , Hu Chunping , Sun Handong , Pu Jianxin , Cao Peng 
Published: December 2016

Abstract
Aberrant expression of thioredoxin 1 (Trx1) plays an important role in cancer initiation and progression and has gained attention as an anticancer drug target. Here we report that the recently discovered natural diterpenoid isoforretin A (IsoA) significantly inhibits Trx1 activity and mediates anticancer effects in multiple preclinical settings. The inhibitory effect of IsoA was antagonized by free radical scavengers polyethylene glycol-catalase, polyethylene glycol superoxide dismutase, thiol-based antioxidants N-acetylcysteine and glutathione. Mass spectrometry analysis revealed that the mechanism of action was based on direct conjugation of IsoA to the Cys32/Cys35 residues of Trx1. This conjugation event attenuated reversible thiol reduction of Trx1, leading to ROS accumulation and a broader degradation of thiol redox homeostasis in cancer cells. Extending these in vitro findings, we documented that IsoA administration inhibited the growth of HepG2 tumors in a murine xenograft model of hepatocellular carcinoma. Taken together, our findings highlight IsoA as a potent bioactive inhibitor of Trx1 and a candidate anticancer natural product. Cancer Res; 77(4); 926–36. ©2016 AACR.
Wnt5a Drives an Invasive Phenotype in Human Glioblastoma Stem-like Cells
Authors: Binda Elena , Visioli Alberto , Giani Fabrizio , Trivieri Nadia , Palumbo Orazio , Restelli Silvia , Dezi Fabio , Mazza Tommaso , Fusilli Caterina , Legnani Federico , Carella Massimo , Di Meco Francesco , Duggal Rohit , Vescovi Angelo L. 
Published: December 2016

Abstract
Brain invasion by glioblastoma determines prognosis, recurrence, and lethality in patients, but no master factor coordinating the invasive properties of glioblastoma has been identified. Here we report evidence favoring such a role for the noncanonical WNT family member Wnt5a. We found the most invasive gliomas to be characterized by Wnt5a overexpression, which correlated with poor prognosis and also discriminated infiltrating mesenchymal glioblastoma from poorly motile proneural and classical glioblastoma. Indeed, Wnt5a overexpression associated with tumor-promoting stem-like characteristics (TPC) in defining the character of highly infiltrating mesenchymal glioblastoma cells (Wnt5aHigh). Inhibiting Wnt5a in mesenchymal glioblastoma TPC suppressed their infiltrating capability. Conversely, enforcing high levels of Wnt5a activated an infiltrative, mesenchymal-like program in classical glioblastoma TPC and Wnt5aLow mesenchymal TPC. In intracranial mouse xenograft models of glioblastoma, inhibiting Wnt5a activity blocked brain invasion and increased host survival. Overall, our results highlight Wnt5a as a master regulator of brain invasion, specifically TPC, and they provide a therapeutic rationale to target it in patients with glioblastoma. Cancer Res; 77(4); 996–1007. ©2016 AACR.
A Novel Mouse Model to Study Image-Guided, Radiation-Induced Intestinal Injury and Preclinical Screening of Radioprotectors
Authors: Verginadis Ioannis I. , Kanade Rahul , Bell Brett , Koduri Sravya , Ben-Josef Edgar , Koumenis Constantinos 
Published: December 2016

Abstract
Radiation is an important treatment modality for gastrointestinal tumors, but intestinal injury is a common side effect. Here we describe a physiologically relevant model for studying the molecular determinants of radiation-induced intestinal damage and testing novel radioprotectors. The model employs a radiopaque marker implanted into the surface of the mouse jejunum, serving as a fiducial marker for precise radiation targeting. Mice were imaged with Cone-Beam CT (CBCT) and irradiated (IR) to the marked area using the Small Animal Radiation Research Platform (SARRP). IR-induced damage was acute but reversible and largely restricted to the area of the marker, leaving the surrounding tissues intact. Although whole gut irradiation with these doses caused lethal GI syndrome, focal (5 mm) radiation of the intestine did not cause any weight loss or lethality. However, fibrosis and collagen deposition 4 months post-IR indicated chronic intestinal damage. A separate cohort of mice was treated daily with curcumin, a clinically tested radioprotector, prior to and post-IR. Curcumin-treated mice showed significant decreases in both local and systemic inflammatory cytokine levels and in fibrosis, suggesting it is an effective radioprotector of the intestine. Our results indicate that this model, which emulates clinically relevant intestinal radiation-induced injury, can be used to assess radioprotectors prior to testing in the clinic. Cancer Res; 77(4); 908–17. ©2016 AACR.