Miracle-dz/UniFAR-FTUs huggingface dataset:
A microarray-based DNA methylation study of glioblastoma multiforme

Glioblastoma multiforme (GBM) is the most frequent and devastating primary brain tumor in adults. The presence of epigenetic lesions, like hypermethylation of known tumor suppressor genes such as MGMT, has been widely described in GBM, but to our knowledge, a genome-wide profile of DNA methylation changes in these lethal tumors is not yet available. In the present analysis, we have quantified the DNA methylation level of 1,505 CpG dinucleotides (807 genes) in 87 consecutive GBMs using universal BeadArrays. Supervised cluster analyses identified 25 and seven genes that were respectively hypermethylated and hypomethylated in more than 20% of the cases studied. The most frequently hypermethylated genes were HOXA11, CD81, PRKCDBP, TES, MEST, TNFRSF10A and FZD9, being involved in more than half of the cases. Studying the biological features of hypermethylated genes, we found that the group of genes hypermethylated in GBM was highly enriched (41%, P
OS DESAFIOS PARA A EXPLICAÇÃO E FORMALIZAÇÃO DA GESTÃO DO CONHECIMENTO NA UNIVERSIDADE DO EXTREMO SUL CATARINENSE - UNESC

A gestao do conhecimento e um recurso estrategico para uma sociedade, sendo a sua base constituida pela identificacao, criacao, armazenagem, compartilhamento e utilizacao. Desta forma, uma instituicao de ensino deve pensar em uma estrategia de gestao do conhecimento, levando em conta a sua historia, a sua estrutura organizacional, seus processos operacionais e principalmente os seus ativos intangiveis, ou seja, as pessoas envolvidas na instituicao. Porem, todo este processo possui desafios para tornar este conhecimento explicito e formalizado em uma ambiente educacional. Objetivo: Nesse contexto, o objetivo deste artigo foi identificar os desafios para a explicitacao e formalizacao da gestao do conhecimento na Universidade do Extremo Sul Catarinense – UNESC. Metodos: Quanto aos fins, a pesquisa foi caracterizada como descritiva e quanto aos meios de investigacao bibliografica e de campo. A coleta de dados foi realizada por meio de uma entrevista semi-estruturada junto a Pro-Reitoria de Administracao e Financas da UNESC. Resultados: Desta forma, verificou-se que o processo de gestao de conhecimento na universidade em estudo, requer acoes eficazes para explicitar, disseminar e formalizar o conhecimento em todo o seu complexo universitario.
Tratamiento psicológico de la impulsividad desde la perspectiva de las terapias de conducta de tercera generación. A propósito de un caso

Objetivo: en el presente trabajo se muestran algunos aspectos claves del tratamiento, en un centro publico de la Comunidad de Madrid, de un sujeto policonsumidor de drogas ilegales con importantes conductas impulsivas. Metodo: la intervencion realizada se enmarca en el paradigma conductista, utilizando herramientas caracteristicas de las terapias de conducta de tercera generacion. En este sentido, se utilizo la relacion terapeutica como el contexto en el que aplicar contingencias que alteraran las relaciones funcionales problematicas. Tambien se emplearon el rol-playing, exposiciones planificadas a circunstancias en donde el paciente pretendia poner en marcha alternativas de respuesta, e instrucciones a los educadores del piso de tratamiento en el que residia. Toda esta intervencion psicologica se realizo en el marco de un tratamiento multidisciplinar, en donde el trabajador social y el medico tuvieron un papel relevante. Resultados: dicha intervencion permitio la recuperacion significativa del paciente en sus areas vitales importantes y el logro de los objetivos terapeuticos. Discusion: con esta exposicion se pretende mostrar la utilidad, para el abordaje de la conducta impulsiva, de la tecnologia conductual y del planteamiento de objetivos diferentes a los habituales en otros modelos terapeuticos
Angiosome Territories of the Nerves of the Lower Limbs

This anatomical study involved the meticulous dissection of three fresh cadaveric specimens to characterize the vascular supply of the nerves of the lower limb. The findings demonstrated that the nerves were supplied segmentally by source vessels, which were color-coded to match the corresponding angiosomes. The segments were then classified into five categories according to whether the nerves and source vessels were branched or unbranched, which has clinical relevance for harvesting of nerves for vascularized nerve transfers.
Fluctuations in interacting particle systems: a theoretical study

[spa] La presente tesis doctoral, se centra en el desarrollo de metodos matematicos para el estudio de procesos estocasticos de interes en fisica y otras ciencias naturales. Fundamentalmente se consideran sistemas de particulas en interaccion, prestando especial atencion al efecto de la heterogeneidad entre los componentes del sistema, asi como el retraso en las interacciones. Tambien se estudian propiedades de sincronizacion en sistemas de elemenentos excitables no identicos. Se desarrollan diversos metodos analiticos para estudiar este tipo de sistemas y se derivan diversos resultados matematicos, algunos exactos y otros aproximados, relevantes para el entendimiento general de este tipo de sitemas. Los metodos desarrollados son aplicados al estudio de diversos sistemas concretos, de interes en expresion genetica, epidemiologia o economia
Coordinated expression and amplification of the MDM2, CDK4, and HMGI‐C genes in atypical lipomatous tumours

Atypical lipomatous tumours (ALTs) represent a distinctive subset of mesenchymal neoplasms featuring mature adipocytic differentiation. Most ALTs are characterized cytogenetically by the presence of supernumerary ring and/or long marker chromosomes derived from the chromosomal region 12q13–15. The 12q13–15 chromosome region contains several genes which may play an important role in human tumorigenesis. A series of ALTs was analysed by investigating the MDM2, CDK4, and HMGI‐C genes and their proteins. The study was extended to a series of ordinary lipomas, to determine whether the immunohistochemical investigation of these gene products might play any diagnostic role. Cytogenetic analysis revealed the presence of various cytogenetic aberrations involving the 12q13–15 region in 11/18 (61%) lipomas and of ring chromosomes in all ALTs. Overexpression of mdm2 protein was observed in 6/12 (50%) atypical lipomatous tumours. All lipomas were mdm2‐negative. cdk4 overexpression was present in 100% of ALTs. Weak cdk4 immunopositivity was detected in 2/18 (11%) ordinary lipomas in a minority of cells. HMGI‐C immunopositivity was observed in 10/12 (83%) ALTs. Positive immunoreactivity was also observed in 8/18 (44%) lipomas. Southern blot analysis revealed amplification of the CDK4 and MDM2 genes in 3/5 ALTs analysed. HMGI‐C was amplified in 3/5 cases and was deleted in one case. Mutation analysis of the CDK4 gene did not demonstrate any mutation. These data support the hypothesis that ordinary lipomas may form a molecular genetic and morphological continuum with ALT. At one end of the spectrum are lipomas characterized by 12q13–15 rearrangements and HMGI‐C activation and at the other end are ALTs with ring chromosomes, 12q13–15 amplification with overrepresentation of the HMGI‐C, CDK4 or MDM2 genes, and aberrant cdk4, mdm2, and HMGI‐C protein expression. These findings not only provide insights into the molecular pathogenesis of lipomatous tumours, but also indicate that the immunohistochemical analysis of mdm2 and cdk4 may help to increase diagnostic accuracy. Copyright © 2000 John Wiley & Sons, Ltd.
The Ras-related protein Cdc42Hs and bradykinin promote formation of peripheral actin microspikes and filopodia in Swiss 3T3 fibroblasts

The Ras-related protein Cdc42 plays a role in yeast cell budding and polarity. Two related proteins, Rac1 and RhoA, promote formation in mammalian cells of membrane ruffles and stress fibers, respectively, which contain actin microfilaments. We now show that microinjection of the related human Cdc42Hs into Swiss 3T3 fibroblasts induced the formation of peripheral actin microspikes, determined by staining with phalloidin. A proportion of these microspikes was found to be components of filopodia, as analyzed by time-lapse phase-contrast microscopy. The formation of filopodia was also found to be promoted by Cdc42Hs microinjection. This was followed by activation of Rac1-mediated membrane ruffling. Treatment with bradykinin also promoted formation of microspikes and filopodia as well as subsequent effects similar to that seen upon Cdc42Hs microinjection. These effects of bradykinin were specifically inhibited by prior microinjection of dominant negative Cdc42HsT17N, suggesting that bradykinin acts by activating cellular Cdc42Hs. Since filopodia have been ascribed an important sensory function in fibroblasts and are required for guidance of neuronal growth cones, these results indicate that Cdc42Hs plays an important role in determining mammalian cell morphology.
Studies on the Scheme of Voltage Control Regulator

Recent power system events have shown that voltage collapse can be a root cause of some widespread outages. The thrust of this paper is to discuss some means of mitigating system voltage depressions that are available through the scheme which utilizes both reactive current droop compensation and line drop compensation. The point that the voltage regulator controls can be acquired by a new method which is based on a widely accepted voltage stability analysis tool. This tool can determine which generators will have an impact on the maximum permissible loading of a bus and which will not. The dynamic analyses were carried out on the CIGRE Nordic test system to study the impact of control point location on time to collapse and prove that the new scheme can improve the voltage stability.
Vasopressin deficiency and vasodilatory state in end-stage liver disease.

OBJECTIVES Relative vasopressin deficiency, a contributor to vasodilatory septic shock, also may be a cause of the vasodilatory state in liver disease. This study assessed endogenous vasopressin levels in patients with liver disease and their hemodynamic response to exogenous vasopressin. DESIGN A prospective, observational study. SETTING A single-center, tertiary hospital. PARTICIPANTS Human subjects undergoing liver transplantation or major surgery. INTERVENTIONS Vasopressin levels were measured in 28 patients with liver disease undergoing liver transplantation and 7 control patients with normal liver function. Additionally, intravenous vasopressin was administered to 20 liver transplant recipients, and the hemodynamic response was observed. MEASUREMENTS AND MAIN RESULTS Patients with liver disease had significantly lower baseline vasopressin levels than controls (19.3 ± 27.1 pg/mL v 50.9 ± 36.7 pg/mL, p = 0.015). Patients with low vasopressin levels (≤20 pg/mL) were more likely to have lower baseline mean blood pressure (≤80 mmHg) than patients with high vasopressin levels (11/16 v 0/4, p = 0.013). Systemic vascular resistance increased by 33% 3 minutes after intravenous vasopressin. Thirteen of 16 patients with low vasopressin levels compared with 1 of 4 patients with high vasopressin levels responded to exogenous vasopressin, with an increase of mean blood pressure by more than 20% (p = 0.028). CONCLUSIONS Patients with liver disease have lower vasopressin levels than controls and respond with a brisk vasoconstrictor response to exogenous vasopressin. Therefore, relative endogenous vasopressin deficiency may contribute to vasodilatory shock in liver disease similar to what has been observed in septic shock.
Productivity costs associated with cardiometabolic risk factor clusters in the United States.

OBJECTIVE Cardiometabolic risk factors such as overweight/obesity, hyperlipidemia, diabetes, and hypertension are prone to cluster together in the same individual and result in an elevated risk of cardiovascular disease and mortality. The purpose of this study was to examine and quantify the impact of cardiometabolic risk factor clusters independent of heart disease on productivity in a nationally representative sample of US adults. METHODS The current study estimated the impact of cardiometabolic risk factor clusters on missed work days and bed days, controlling for sociodemographic characteristics, comorbidity, and smoking status in a nationally representative, pooled 2000 and 2002 Medical Expenditure Panel Survey sample. Cardiometabolic risk factor clusters included BMI >or= 25 and two of the following three: diabetes, hyperlipidemia, and/or hypertension. All estimates were expressedin $US 2005. Sensitivity analyses were conducted to examine the impact of varying assumptions on the results. RESULTS After controlling for differences in sociodemographics, smoking and comorbidity, individuals with cardiometabolic risk factor clusters missed 179% more work days and spent 147% more days in bed (in addition to lost work days) than those without. Lost work days and bed days resulted in $17.3 billion annually in lost productivity attributable to cardiometabolic risk factor clusters in the United States. Sensitivity analyses resulted in a range of annual lost productivity costs from $3.2 to $23.1 billion. CONCLUSIONS Common cardiometabolic risk factor clusters have a significant deleterious impact on the US economy, resulting in $17.3 billion in lost productivity.
A review of Haemophilus influenzae disease in Europe from 2000–2014: challenges, successes and the contribution of hexavalent combination vaccines

ABSTRACT Introduction: The development of diphtheria-tetanus-acellular pertussis-Haemophilus influenzae type b (Hib) conjugate vaccine combinations culminated with hexavalent vaccines, the largest, most complex vaccine combinations in the immunization calendar. Hexavalent vaccines are used widely in Europe and are co-administered with multiple other recommended vaccines. Hib immunogenicity may reduce when combined with acellular pertussis antigens, or in some co-administrations. We reviewed the epidemiology of H. influenzae disease in Europe aiming to evaluate the current level of Hib control and indirectly assess the effectiveness against Hib of GSK’s hexavalent vaccine in 10 countries where it is/has been used almost exclusively. Areas covered: We reviewed surveillance data from the European Union Invasive Bacterial Infections Surveillance Network and the European Surveillance System database from 1999–2014 and extracted case and incidence/notification rates (per 100,000 population) of invasive H. influenzae disease. We included age and serotype/strains distribution among countries in the European Union/European Economic Area region that reported to the European Centre for Disease Prevention and Control surveillance system. Expert commentary: The impact of Hib vaccination in Europe is sustained, testifying to continued effectiveness against invasive Hib disease after the implementation of hexavalent vaccines into immunization programs, which, since 2006, has been almost exclusively GSK´s hexavalent DTPa-HBV-IPV/Hib vaccine.
Handling missing data in survey research

Missing data occur in survey research because an element in the target population is not included on the survey's sampling frame (noncoverage), because a sampled element does not participate in the survey (total nonresponse) and because a responding sampled element fails to provide acceptable responses to one or more of the survey items (item nonresponse). A variety of methods have been developed to attempt to compensate for missing survey data in a general purpose way that enables the survey's data file to be analysed without regard for the missing data. Weighting adjustments are often used to compensate for noncoverage and total nonresponse. Imputation methods that assign values for missing responses are used to compensate for item nonresponses. This paper describes the various weighting and imputation methods that have been developed, and discusses their benefits and limitations.
Treatment with tumor necrosis factor blockers is associated with a lower incidence of first cardiovascular events in patients with rheumatoid arthritis.

OBJECTIVE To investigate the risk of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor (TNF) inhibitors, compared to a standard RA population. METHODS Patients were recruited from a regional register, which includes over 90% of patients with RA started on TNF blockers in 1999 or later, and a local community based cohort of RA patients, established in 1997. Of a total of 983 patients in the combined cohort, 531 received treatment with etanercept or infliximab during the study period. The total cohort (n = 983) was linked with national registers for inpatient care and cause of death through December 31, 2001. CVD was defined as the first inpatient care or death from CVD without inpatient care for CVD prior to study entry. First CVD events in those treated versus not treated with TNF blockers were estimated, using age and sex adjusted incidence density computations with treatment and disease severity markers as time-dependent covariates. RESULTS In the anti-TNF-treated patients, the age-sex adjusted incidence rate of first CVD event was 14.0/1000 person-years at risk (95% CI 5.7-22.4), compared with 35.4/1000 person-years (95% CI 16.5-54.4) in those not treated. Controlling for disability, the age-sex adjusted rate ratio was 0.46 (95% CI 0.25-0.85, p = 0.013) in anti-TNF-treated versus not treated. CONCLUSION These findings suggest that the risk of developing CVD is lower in patients with RA treated with TNF blockers. This is compatible with the hypothesis that inflammation contributes to the development of cardiovascular events.
A push for quieter ships.

Over the past 4 years, studies at the Gerry E. Studds Stellwagen Bank National Marine Sanctuary off the coast of Massachusetts have documented how human activities are ramping up the region9s undersea noise—and highlighted just how difficult it may be to turn down the volume. Stellwagen9s monitoring program, one of the world9s most intensive, has implications well beyond the marine sanctuary. It has helped focus attention on the growing acoustic clutter created by the world9s nearly 100,000 large commercial ships. Although other sources of ocean noise—including military sonar, pile drivers, and the undersea air guns that scientists and energy companies use to map the sea floor—have generated more controversy because of the risks to sea life, researchers say everyday ship traffic is arguably the sea9s most pressing sound problem.
Evidence for autosomal dominant inheritance of prostate cancer.

A family-history cancer survey was conducted on 5,486 men who underwent a radical prostatectomy, for clinically localized prostate cancer, in the Department of Urology at the Mayo Clinic during 1966-95; 4,288 men responded to the survey. Complex segregation analysis was performed to assess the genetic basis of age at diagnosis and the familial clustering of prostate cancer. For the total group, no single-gene model of inheritance clearly explained familial clustering of disease, which could be partly explained by lack of Hardy-Weinberg equilibrium, with an excess of homozygotes. After accounting for deviations from Hardy-Weinberg equilibrium, the best-fitting model that explained the familial aggregation and age at diagnosis was a rare autosomal dominant susceptibility gene, and this model fitted best when probands were diagnosed at <60 years of age. The model predicts that the frequency of the susceptibility gene in the population is . 006 and that the risk of prostate cancer by age 85 years is 89% among carriers of the gene and 3% among noncarriers. A strength of our study is its large size, such that genetic models could be fitted within strata defined by the age of the proband. Although the autosomal dominant model was consistently the best model, the parameter estimates differed somewhat (P=.03) across the different age groups, suggesting genetic heterogeneity. Additional evidence that the hereditary basis of prostate cancer is likely to be genetically complex was provided by the following: (1) there was a significantly elevated age-adjusted risk of prostate cancer among brothers of probands, compared with their fathers (relative risk 1.5 [95% confidence interval 1.4-1.7]); (2) the autosomal dominant model predicted an excess of homozygotes, over that predicted by Hardy-Weinberg equilibrium; and (3) the model-predicted risk of prostate cancer among relatives was inadequate when probands were diagnosed at age >=70 years.
Human MutY Homolog, a DNA Glycosylase Involved in Base Excision Repair, Physically and Functionally Interacts with Mismatch Repair Proteins Human MutS Homolog 2/Human MutS Homolog 6*

Adenines mismatched with guanines or 7,8-dihydro-8-oxo-deoxyguanines that arise through DNA replication errors can be repaired by either base excision repair or mismatch repair. The human MutY homolog (hMYH), a DNA glycosylase, removes adenines from these mismatches. Human MutS homologs, hMSH2/hMSH6 (hMutSα), bind to the mismatches and initiate the repair on the daughter DNA strands. Human MYH is physically associated with hMSH2/hMSH6 via the hMSH6 subunit. The interaction of hMutSα and hMYH is not observed in several mismatch repair-defective cell lines. The hMutSα binding site is mapped to amino acid residues 232–254 of hMYH, a region conserved in the MutY family. Moreover, the binding and glycosylase activities of hMYH with an A/7,8-dihydro-8-oxo-deoxyguanine mismatch are enhanced by hMutSα. These results suggest that protein-protein interactions may be a means by which hMYH repair and mismatch repair cooperate in reducing replicative errors caused by oxidized bases.
Intra-endosomal pH-sensitive Recruitment of the Arf-nucleotide Exchange Factor ARNO and Arf6 from Cytoplasm to Proximal Tubule Endosomes*

Kidney proximal tubule epithelial cells have an extensive apical endocytotic apparatus that is critical for the reabsorption and degradation of proteins that traverse the glomerular filtration barrier and that is also involved in the extensive recycling of functionally important apical plasma membrane transporters. We show here that an Arf-nucleotide exchange factor, ARNO (ADP-ribosylation factor nucleotide site opener) as well as Arf6 and Arf1 small GTPases are located in the kidney proximal tubule receptor-mediated endocytosis pathway, and that ARNO and Arf6 recruitment from cytosol to endosomes is pH-dependent. In proximal tubules in situ, ARNO and Arf6 partially co-localized with the V-ATPase in apical endosomes in proximal tubules. Arf1 was localized both at the apical pole of proximal tubule epithelial cells, but also in the Golgi. By Western blot analysis ARNO, Arf6, and Arf1 were detected both in purified endosomes and in proximal tubule cytosol. A translocation assay showed that ATP-driven endosomal acidification triggered the recruitment of ARNO and Arf6 from proximal tubule cytosol to endosomal membranes. The translocation of both ARNO and Arf6 was reversed by V-type ATPase inhibitors and by uncouplers of endosomal intralumenal pH, and was correlated with the magnitude of intra-endosomal acidification. Our data suggest that V-type ATPase-dependent acidification stimulates the selective recruitment of ARNO and Arf6 to proximal tubule early endosomes. This mechanism may play an important role in the pH-dependent regulation of receptor-mediated endocytosis in proximal tubulesin situ.
Counting Whales in the North Atlantic

In their Report “Whales before whaling in the North Atlantic” (25 July, p. [508][1]), J. Roman and S. R. Palumbi conclude, using genetic markers, that humpback, minke, and fin whale populations in the North Atlantic were once much larger than previously thought, which goes against the current