bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resistin promotes cardiac homing of mesenchymal stem cells and functional recovery after myocardial ischemia-reperfusion via the ERK1/2-MMP-9 pathway
Authors: He Yuan , Guo Yanjie , Xia Yunlong , Guo Yongzhen , Wang Rutao , Zhang Fuyang , Guo Lanyan , Liu Yi , Yin Tao , Gao Chao , Gao Erhe , Li Congye , Wang Shan , Zhang Ling , Yan Wenjun , Tao Ling 
Published: November 2018

Stem cell therapy is a potentially effective and promising treatment for ischemic heart disease. Resistin, a type of adipokine, has been found to bind to adipose-derived mesenchymal stem cells (ADSCs). However, the effects of resistin on cardiac homing by ADSCs and on ADSC-mediated cardioprotective effects have not been investigated. ADSCs were obtained from enhanced green fluorescent protein transgenic mice. C57BL/6J mice were subjected to myocardial ischemia-reperfusion (I/R) or sham operations. Six hours after the I/R operation, mice were intravenously injected with resistin-treated ADSCs (ADSC-resistin) or vehicle-treated ADSCs (ADSC-vehicle). Cardiac homing by ADSCs and cardiomyocyte apoptosis were investigated 3 days after I/R. Cardiac function, fibrosis, and angiogenesis were evaluated 4 wk after I/R. Cellular and molecular mechanisms were investigated in vitro using cultured ADSCs. Both immunostaining and flow cytometric experiments showed that resistin treatment promoted ADSC myocardial homing 3 days after intravenous injection. Echocardiographic experiments showed that ADSC-resistin, but not ADSC-vehicle, significantly improved left ventricular ejection fraction. ADSC-resistin transplantation significantly mitigated I/R-induced fibrosis and reduced atrial natriuretic peptide/brain natriuretic peptide mRNA expression. In addition, cardiomyocyte apoptosis was reduced, whereas angiogenesis was increased by ADSC-resistin treatment. At the cellular level, resistin promoted ADSC proliferation and migration but did not affect H2O2-induced apoptosis. Molecular experiments identified the ERK1/2-matrix metalloproteinase-9 pathway as a key component mediating the effects of resistin on ADSC proliferation and migration. These results demonstrate that resistin can promote homing of injected ADSCs into damaged heart tissue and stimulate functional recovery, an effect mediated through the ERK1/2 signaling pathway and matrix metalloproteinase-9. NEW & NOTEWORTHY First, intravenous injection of adipose-derived mesenchymal stem cells (ADSCs) treated with resistin significantly increased angiogenesis and reduced myocardial apoptosis and fibrosis in a murine model of ischemia-reperfusion, resulting in improved cardiac performance. Second, resistin treatment significantly increased myocardial homing of intravenously delivered ADSCs. Finally, the ERK1/2-matrix metalloproteinase 9 pathway contributed to the higher proliferative and migratory capacities of ADSCs treated with resistin.
Frequent Homologous Recombination Deficiency in High-grade Endometrial Carcinomas
Authors: de Jonge Marthe M. , Auguste Aurélie , van Wijk Lise M. , Schouten Philip C. , Meijers Matty , ter Haar Natalja T. , Smit Vincent T.H.B.M. , Nout Remi A. , Glaire Mark A. , Church David N. , Vrieling Harry , Job Bastien , Boursin Yannick , de Kroon Cor D. , Rouleau Etienne , Leary Alexandra , Vreeswijk Maaike P.G. , Bosse Tjalling 
Published: November 2018

AbstractPurpose:The elevated levels of somatic copy-number alterations (SCNAs) in a subset of high-risk endometrial cancers are suggestive of defects in pathways governing genome integrity. We sought to assess the prevalence of homologous recombination deficiency (HRD) in endometrial cancers and its association with histopathologic and molecular characteristics.Experimental Design:Fresh tumor tissue was prospectively collected from 36 endometrial cancers, and functional HRD was examined by the ability of replicating tumor cells to accumulate RAD51 protein at DNA double-strand breaks (RAD51 foci) induced by ionizing radiation. Genomic alterations were determined by next-generation sequencing and array comparative genomic hybridization/SNP array. The prevalence of BRCA-associated genomic scars, a surrogate marker for HRD, was determined in the The Cancer Genome Atlas (TCGA) endometrial cancer cohort.Results:Most endometrial cancers included in the final analysis (n = 25) were of non-endometrioid (52%), grade 3 (60%) histology, and FIGO stage I (72%). HRD was observed in 24% (n = 6) of cases and was restricted to non-endometrioid endometrial cancers (NEEC), with 46% of NEECs being HRD compared with none of the endometrioid endometrial cancers (EEC, P = 0.014). All but 1 of the HRD cases harbored either a pathogenic BRCA1 variant or high somatic copy-number (SCN) losses of HR genes. Analysis of TCGA cases supported these results, with BRCA-associated genomic scars present in up to 48% (63/132) of NEEC versus 12% (37/312) of EEC (P &lt; 0.001).Conclusions:HRD occurs in endometrial cancers and is largely restricted to non-endometrioid, TP53-mutant endometrial cancers. Evaluation of HRD may help select patients that could benefit from treatments targeting this defect, including platinum compounds and PARP inhibitors.
Pleiotropic Action of Novel Bruton's Tyrosine Kinase Inhibitor BGB-3111 in Mantle Cell Lymphoma
Authors: Li Carrie J. , Jiang Changying , Liu Yang , Bell Taylor , Ma Wencai , Ye Yin , Huang Shengjian , Guo Hui , Zhang Hui , Wang Lai , Wang Jing , Nomie Krystle , Zhang Liang , Wang Michael 
Published: November 2018

Abstract
Bruton's tyrosine kinase (BTK) is a key mediator of BCR-dependent cell growth signaling and a clinically effective therapeutic target in mantle cell lymphoma (MCL). The molecular impact of BTK inhibition remains unclear particularly in hematopoietic malignancies. We analyzed the molecular mechanisms of BTK inhibition with the novel inhibitor BGB-3111 (zanubrutinib) in MCL models. The efficacy of BGB-3111 was investigated using growth proliferation/cell viability and apoptosis assays in MCL cell lines and patient-derived xenograft (PDX) MCL cells. The activity and mechanisms of BGB-3111 were further confirmed using a cell line xenograft model, an MCL PDX mouse model, and a human phosphokinase profiler array and reverse phase protein array. Finally, the mechanisms related to resistance to BTK inhibition were analyzed by creating cell lines with low levels of BTK using CRISPR/Cas 9 genome editing. We found that inhibition of BTK leads to suppression of tumor growth, which was mediated via potent suppression of AKT/mTOR, apoptosis, and metabolic stress. Moreover, targeted disruption of the BTK gene in MCL cells resulted in resistance to BTK inhibition and the emergence of novel survival mechanisms. Our studies suggest a general efficacy of BTK inhibition in MCL and potential drug resistance mechanism via alternative signaling pathways.
Dados geoquímicos e gamaespectrométricos na avaliação do potencial de corpos ígneos brasilianos para gerar concentrações de elementos terras raras do tipo ion adsorption clay (Terreno Apiaí-Guaxupé, estados de Minas Gerais e São Paulo, Brasil)
Authors: Faria Júnior Ilio Rodarte , Luvizzoto George Luiz , Godoy Antonio Misson 
Published: November 2018

Os elementos terras raras apresentam crescente importância na economia mundial devido as suas aplicações na indústria de tecnologia, resultando em um crescente interesse pela prospecção de fontes minerais para esses elementos. Nesse âmbito, um tipo particular de mineralização conhecido na China se destaca por representar a principal fonte de elementos terras raras pesados (Eu a Lu) e ítrio (Y), menos comuns do que de elementos terras raras leves (La a Sm). Esse tipo de depósito, denominado ion adsorption clay, é composto de perfis de intemperismo desenvolvidos a partir de biotita e/ou muscovita sienogranitos, com a concentração exógena dos elementos terras raras originando-se pela adsorção desses elementos em argilominerais neoformados pelo processo intempérico. Características diversas afetam a gênese desses depósitos, onde a presença de minerais de elementos terras raras muito susceptíveis ao intemperismo e as características de desenvolvimento da alteração exógena são de grande importância para esse tipo de enriquecimento de elementos terras raras. O Terreno Apiaí-Guaxupé, onde foram selecionados corpos ígneos para a presente avaliação, é portador de uma diversidade de corpos ígneos, os quais foram afetados por processos de intemperismo cenozóicos, representando uma região com potencial prospectivo para esse tipo de depósito. Os corpos ígneos avaliados não apresentam informações descritivas sobre minerais (fluor)carbonáticos de elementos terras raras, muito susceptíveis ao intemperismo e importantes para a gênese desses depósitos de concentração exógena. Dessa forma, faz-se necessário o uso de informações químicas, descrições de minerais acessórios e de sobreposição de processos de alteração hidrotermal na busca de definir a possibilidade de formação dos minerais (fluor)carbonáticos de elementos terras raras. A investigação da potencialidade de enriquecimento de elementos terras raras do tipo
Initial psychometric evaluation of the Community Participation Activation Scale
Authors: Lee Danbi , Mallinson Trudy , Baum Carolyn M. , Hammel Joy 
Published: November 2018

Background. Current assessments do not capture the dynamic and complex process of managing different individual and environmental factors influencing community participation post-stroke. Purpose. The purpose of this study was to examine the psychometric properties of the Community Participation Activation Scale (CPAS) in persons with stroke. Method. Rating scale structure, unidimensionality, reliability and precision, construct validity, and differential item functioning of the CPAS were examined with 93 community-dwelling people with stroke. Findings. The CPAS consists of 15 action items and 10 attitude items. Person separation reliabilities of the action and attitude domains were .75 and .72, respectively, and internal consistency reliabilities were good (>.80). The CPAS showed low to moderate correlation with community integration and enfranchisement constructs. Implications. The CPAS may be used as an assessment to better understand an individual’s level of activation and to inform individually designed, participation-focused interventions, although it needs further improvement to be used as a clinical measure.
Beyond tobacco prevention: A qualitative study of a school-based life skills intervention for economically disadvantaged youth in Mumbai, India
Authors: Nagler Eve M , Lobo Priya 
Published: November 2018

Objective: Low socioeconomic status young people in low- and middle-income countries use tobacco at higher rates than their wealthier peers. School-based tobacco use prevention interventions that employ a life skills approach are effective at preventing tobacco use. In India, the Salaam Bombay Foundation (SBF) has implemented a multiyear, multicomponent life skills education programme in Mumbai schools to prevent tobacco use. A quantitative evaluation found that SBF programme exposure was associated with not only reduced tobacco use but also improved life skills, self-esteem and self-efficacy. To illuminate how programme exposure engendered these effects, we compared the experiences and perceptions of eighth and ninth grade students (ages 13–15) between SBF and non-SBF schools. Methods: We divided Mumbai into four quadrants or regions and randomly selected one SBF and non-SBF school from each quadrant; 10 participants were then randomly selected from one class per school. A total of eight group discussions ( N = 80 participants) were conducted using mind-mapping with a focus on students’ daily life, future aspirations and non-academic school programming. Researchers analysed the data thematically. Results: Despite similar home lives, SBF students were profoundly more optimistic about their future than non-SBF students. SBF students attributed this increased optimism and agency to opportunities to actively advocate against tobacco, formal recognition in a published newsletter, a sense of belonging to a ‘Super Army’ and supportive mentorship provided by their Super Army and peer leaders. The SBF programme created a safe space in which to build resilience. Conclusion: These findings can guide development of programmes for vulnerable populations with broader goals than tobacco prevention.
The Transformative Potential of Constituent Power: A Revised Approach to the New Latin American Constitutionalism
Authors: Hughes Carys 
Published: November 2018

The processes of constitutional change and resultant constitutional models initiated in Venezuela, Bolivia, and Ecuador since the late 1990s have been celebrated for offering a democratic form of constitutionalism. The new Latin American constitutionalism promises to resolve the democratic deficit in traditional constitutional theory by institutionalizing spaces for citizen-led constitutional change. However, events in which actors outside the state or without the wider support of the state have attempted to initiate similar processes of constitutional transformation suggest a problem with current theories. This is a residual bias toward state actors and a tendency to underestimate the power of extrainstitutional actors in these processes. By reconceiving the central concepts of “constituent power” and “constitutional process,” an account of the new Latin American constitutionalism is possible that both resolves remaining tensions in the literature and illustrates the relevance of this phenomenon to struggles across the continent. Los procesos de cambio constitucional y los modelos constitucionales resultantes iniciados en Venezuela, Bolivia y Ecuador desde fines de la década de 1990 se han celebrado por ofrecer una forma democrática de constitucionalismo. El nuevo constitucionalismo latinoamericano promete resolver el déficit democrático en la teoría constitucional tradicional mediante la institucionalización de espacios para el cambio constitucional liderado por los ciudadanos. Sin embargo, eventos en los cuales actores fuera del estado o sin el apoyo más amplio del estado han intentado iniciar procesos similares de transformación constitucional sugieren un problema con las teorías actuales. Este es un sesgo residual hacia los actores estatales y una tendencia a subestimar el poder de los actores extrainstitucionales en estos procesos. Al reconcebir los conceptos centrales del “poder constituyente” y el “proceso constitucional,” es posible hacer un recuento del nuevo constitucionalismo latinoamericano que resuelve las tensiones restantes en la literatura y demuestra la relevancia de este fenómeno para luchas en todo el continente.
Mitochondrial DNA haplogroups influence the risk of aortic stenosis
Authors: Serrano-Teruel Maria E. , Garcia-Vieites Maria , Rego-Perez Ignacio , Domenech-Garcia Nieves , Blanco-Garcia Francisco , Cuenca-Castillo Jose J. , Bautista-Hernandez Victor 
Published: November 2018

Aim The underlying pathophysiologic mechanisms of aortic stenosis are not clear. Mitochondrial dysfunction plays a role in many pathological conditions including cardiac diseases. We aimed to analyze the mitochondrial DNA haplogroups in a group of patients undergoing valve replacement surgery due to severe aortic stenosis. Methods Mitochondrial DNA haplogroups were assessed in 176 patients with severe aortic stenosis and 308 control subjects. Cardiovascular risk factors and demographics were similar in both groups. Results Patients carrying haplogroup Uk had a lower risk of developing aortic stenosis, especially compared to patients carrying haplogroup H (odds ratio = 0.507; 95% confidence interval: 0.270–0.952, p = 0.035). Conclusions Mitochondrial DNA haplogroups could be involved in the development of severe aortic stenosis. Specifically, haplogroup H could be a risk factor and Uk a protective factor for severe aortic stenosis in a population from Spain.
Scanning training for rehabilitation of visual field loss due to stroke: Identifying and exploring training tools in use
Authors: Hazelton Christine , Pollock Alex , Walsh Glyn , Brady Marian C 
Published: November 2018

Introduction Visual field loss affects one fifth of stroke survivors, limiting daily activities and reducing quality of life. Scanning training is a commonly used intervention, but there is variation in how this is delivered. This study aimed to identify the scanning training tools used in Scotland and describe their training parameters, delivery and suitability for use with stroke survivors. Method An email survey identified scanning training tools used in Scotland. Two expert panel meetings gained consensus on the motor, language and cognitive skills required to use each scanning training tool. Video capture techniques gathered objective measures of training parameters. Results Ten scanning training tools were identified. These tools used four delivery methods: paper-based, computer software, web-based and specialised equipment. They aimed to improve reading, perception or general visual skills. Fast, saccadic eye movements were most frequently targeted: two interventions also encouraged head movements. Session duration, frequency and therapist support varied considerably. The level of motor, language and cognitive skills required for each tool was determined. Conclusion Scanning training tools used in Scotland vary in delivery modality, functional abilities required for use and visual skills trained. This information will support clinical decision-making and inform future research on training effectiveness and feasibility.
Effect of microalbuminuria on macular thickness in patients with type-2 diabetes mellitus
Authors: Ucgul Atilgan Cemile , Atilgan Kadir Gokhan , Kosekahya Pinar , Caglayan Mehtap , Sendul Selam Yekta , Yilmazbas Pelin 
Published: November 2018

Purpose: To investigate the effect of microalbuminuria on macular thickness in patients with type-2 diabetes mellitus with no or mild diabetic retinopathy and to investigate the relationship between macular thickness and metabolic parameters. Materials and methods: Fifty eight eyes of 58 patients without diabetic retinopathy (group 1) in microalbuminuria stage, 42 eyes of 42 patients with mild diabetic retinopathy (group 2) in microalbuminuria stage, and 50 eyes of 50 patients without diabetic retinopathy and microalbuminuria (group 3) were included in this study. After detailed ophthalmologic examination, all patients underwent spectral domain-optical coherence tomography measurements. Macular thickness was noted from nine different areas (fovea, four parafoveal, and four perifoveal areas) and compared between groups. The correlations between macular thickness and age, duration of diabetes mellitus, microalbuminuria, serum urea, creatinine, glycosylated hemoglobin (HbAIc), albumin, sodium (Na), and urinary Na were evaluated. Results: The mean age was 53.29 ± 6.49 in group 1, 55.86 ± 6.97 in group 2, and 52.98 ± 5.66 years in group 3 (p = 0.06). The macular thickness values of superior, inferior, and nasal parafoveal areas were significantly different between groups (p = 0.001, p = 0.006, and p = 0.03, respectively). Bonferroni post test revealed that this difference originated from the difference between group 2 and 3 (p < 0.05 for all values). There were significant negative correlations between the macular thickness values of parafoveal areas and serum urea, HbA1c, albumin, microalbuminuria levels (p < 0.05 for all values). Conclusion: In this study, a significantly decreased parafoveal macular thickness was measured in patients with mild diabetic retinopathy and microalbuminuria compared to patients without diabetic retinopathy and microalbuminuria.
Machine Learning With K-Means Dimensional Reduction for Predicting Survival Outcomes in Patients With Breast Cancer
Authors: Zhao Melissa , Tang Yushi , Kim Hyunkyung , Hasegawa Kohei 
Published: November 2018

Objective: Despite existing prognostic markers, breast cancer prognosis remains a difficult subject due to the complex relationships between many contributing factors and survival. This study seeks to integrate multiple clinicopathological and genomic factors with dimensional reduction across machine learning algorithms to compare survival predictions. Methods: This is a secondary analysis of the data from a prospective cohort study of female patients with breast cancer enrolled in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC). We constructed a series of predictive models: ensemble models (Gradient Boosting and Random Forest), support vector machine (SVM), and artificial neural networks (ANN) for 5-year survival based on clinicopathological and gene expression data after K-means clustering with K-nearest-neighbor (KNN) classification. Model performance was evaluated by receiver operating characteristic (ROC) curve, accuracy, and calibration slope (CS). Model stability was assessed over 10 random runs in terms of ROC, accuracy, CS, and variable importance. Results: The analytic cohort is composed of 1874 patients with breast cancer. Overall, the median age was 62 years; the 5-year survival rate was 75%. ROC and accuracy were not significantly different between models (ROC and accuracy around 0.67 and 0.72 across models, respectively). However, ensemble methods resulted in better fit (CS) with stable measures of variable importance across 10 random training/validation splits. K-means clustering of gene expression profiles on training data points along with KNN classification of validation data points was a robust method of dimensional reduction. Furthermore, the gene expression cluster with the highest mortality risk was an influential factor in model prediction. Conclusions: Using machine learning methods to construct predictive models for 5-year survival in patients with breast cancer, we demonstrated discrimination ability across models with new insight into the stability and utility of dimensional reduction on genomic features in breast cancer survival prediction.
Ezetimibe — maximising cholesterol reduction through dual inhibition
Authors: Shepherd James 
Published: November 2018

Statins cannot always bring plasma lipoprotein levels to target because they only attack one element of the cholesterol homoeostatic pathway. By inhibiting cholesterol absorption as well, using ezetimibe, additional benefits may be obtained. Ezetimibe co-administered with low-dose statin may give an additional 10% reduction in triglyceride, 14% reduction in low-density lipoprotein (LDL) cholesterol, and a 5% rise in high-density lipoprotein (HDL) cholesterol compared to statin alone. In one study, significantly better National Cholesterol Education Program goal achievement was seen with co-administration of ezetimibe and a statin compared to statin treatment alone. Ezetimibe plus a statin is generally well tolerated.
Extended dynamometry: reference values
Authors: Belcher Henry J. C. R. , Smith Hayley 
Published: November 2018

Grip strength is used as a measure of capacity in disability and personal injury claims. Although seemingly an objective measure, it is widely recognized that it is fallible to the effects of sub-maximal effort. We have developed an extended test protocol that uses the five positions of a Jamar dynamometer. The protocol mitigates the effect of inconsistency while retaining the ability to detect sub-maximal effort. Dynamometry was undertaken in 242 volunteers (male:female, 124:118) with a median age of 39 years (range 18–89, interquartile range 29–52). Normative values for consistency, curve deviation and variation from the expected curve pattern are provided. None of these measures were significantly affected by laterality, hand dominance, sex or age despite the effects of these variables on grip strength. The study defines the methodology and reference values to allow assessment of both the capacity of a patient and the reliability of the test for use in medicolegal practice. Level of evidence: II