cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.19583824
title: Non-genetic stratification reveals epigenetic heterogeneity and identifies vulnerabilities of glycolysis addiction in lung adenocarcinoma subtype

description: Lung adenocarcinoma (LUAD) exhibits high heterogeneity and is well known for its high genetic variation. Recently, the understanding of non-genetic variation provides a new perspective to study the heterogeneity of LUAD. Little is known about whether super-enhancers (SEs) may be primarily responsible for the inter-tumor heterogeneity of LUAD. We used super-enhancer RNA (seRNA) levels of a large-scale clinical well-annotated LUAD cohort to stratify patients into three clusters with different prognosis and other malignant characteristic. Mechanistically, estrogen related receptor alpha (ERRα) in cluster 3-like cell lines acts as a cofactor of BRD4 to assist SE-promoter loops to activate glycolysis-related target gene expression, thereby promoting glycolysis and malignant progression, which confers a therapeutic vulnerability to glycolytic inhibitors. Our study identified three groups of patients according to seRNA levels, among which patients in cluster 3 have the worst prognosis and vulnerability of glycolysis dependency. We also proposed a 3-TF index model to stratify patients with glycolysis-addicted tumors according to tumor SE stratification.
DOI: 10.6084/m9.figshare.21310317
title: THE OPEN SCHOOL OR VOLUNTEERING AS A PARADIGM OF PARTICIPATION

description: ABSTRACT This paper is aimed at analyzing how the evolution of the functions of volunteering affects the development of a learning community in Burgos (Spain). This research gathers ideas, perceptions and expectations about volunteering in the learning communities, specifically in one that has concentrated a high number of migrant families. A qualitative methodology under the paradigm of Critical Communicative Methodology is used. Representatives of the different groups of educational agents were interviewed. An educational guidance interview was used. The participants highlight the role of the learning community as an innovative model compared to the traditional school. It is necessary to develop strategies for approaching the families from minority cultures that join irregularly in volunteering.
DOI: 10.6084/m9.figshare.21310317.v1
title: THE OPEN SCHOOL OR VOLUNTEERING AS A PARADIGM OF PARTICIPATION

description: ABSTRACT This paper is aimed at analyzing how the evolution of the functions of volunteering affects the development of a learning community in Burgos (Spain). This research gathers ideas, perceptions and expectations about volunteering in the learning communities, specifically in one that has concentrated a high number of migrant families. A qualitative methodology under the paradigm of Critical Communicative Methodology is used. Representatives of the different groups of educational agents were interviewed. An educational guidance interview was used. The participants highlight the role of the learning community as an innovative model compared to the traditional school. It is necessary to develop strategies for approaching the families from minority cultures that join irregularly in volunteering.
DOI: 10.6084/m9.figshare.21213027
title: CYP450 Metabolism of a Semisynthetic Naphthoquinone, an Anticancer Drug Candidate, by Human Liver Microsomes

description: CNFD (6b,7-dihydro-5H-cyclopenta[b]naphtho[2,1-d]furan-5,6(9aH)-dione) is a semisynthetic naphthoquinone derived from lawsone that has cytotoxic action in different tumor lines and anticancer activity in vivo. Therefore, this molecule is a relevant candidate for drug development, but there is still no information on its human metabolism and systemic elimination. This study aimed to investigate the in vitro metabolism of this naphthoquinone by human liver microsomes. Initially, in order to determine the in vitro enzymatic kinetic parameters, a high performance liquid chromatography (HPLC) method to quantify the CNFD was developed and validated. In addition, the enzymatic kinetic data, the predicted pharmacokinetic in vivo parameters and the phenotyping study were presented. The main metabolism sites and metabolites have been suggested in silico. The developed HPLC method was linear, reproducible, selective, accurate, and stable. The enzymatic kinetic parameters revealed a sigmoidal profile. In vitro to in vivo extrapolation hepatic metabolic clearance was 10.39 mL min-1 kg-1 protein and the liver extraction rate was 51%. The clearance in vivo associated with a hepatic extraction ratio indicates that the hepatic metabolism is the main route of elimination. Although all cytochrome P450 enzymes evaluated metabolized CNFD, CYP2C9 and CYP3A4 showed higher metabolic capacity. For the first time, metabolism studies of CNFD were demonstrated.
DOI: 10.6084/m9.figshare.21213027.v1
title: CYP450 Metabolism of a Semisynthetic Naphthoquinone, an Anticancer Drug Candidate, by Human Liver Microsomes

description: CNFD (6b,7-dihydro-5H-cyclopenta[b]naphtho[2,1-d]furan-5,6(9aH)-dione) is a semisynthetic naphthoquinone derived from lawsone that has cytotoxic action in different tumor lines and anticancer activity in vivo. Therefore, this molecule is a relevant candidate for drug development, but there is still no information on its human metabolism and systemic elimination. This study aimed to investigate the in vitro metabolism of this naphthoquinone by human liver microsomes. Initially, in order to determine the in vitro enzymatic kinetic parameters, a high performance liquid chromatography (HPLC) method to quantify the CNFD was developed and validated. In addition, the enzymatic kinetic data, the predicted pharmacokinetic in vivo parameters and the phenotyping study were presented. The main metabolism sites and metabolites have been suggested in silico. The developed HPLC method was linear, reproducible, selective, accurate, and stable. The enzymatic kinetic parameters revealed a sigmoidal profile. In vitro to in vivo extrapolation hepatic metabolic clearance was 10.39 mL min-1 kg-1 protein and the liver extraction rate was 51%. The clearance in vivo associated with a hepatic extraction ratio indicates that the hepatic metabolism is the main route of elimination. Although all cytochrome P450 enzymes evaluated metabolized CNFD, CYP2C9 and CYP3A4 showed higher metabolic capacity. For the first time, metabolism studies of CNFD were demonstrated.
DOI: 10.6084/m9.figshare.21310323
title: Sex in protists: A new perspective on the reproduction mechanisms of trypanosomatids

description: Abstract The Protist kingdom individuals are the most ancestral representatives of eukaryotes. They have inhabited Earth since ancient times and are currently found in the most diverse environments presenting a great heterogeneity of life forms. The unicellular and multicellular algae, photosynthetic and heterotrophic organisms, as well as free-living and pathogenic protozoa represents the protist group. The evolution of sex is directly associated with the origin of eukaryotes being protists the earliest protagonists of sexual reproduction on earth. In eukaryotes, the recombination through genetic exchange is a ubiquitous mechanism that can be stimulated by DNA damage. Scientific evidences support the hypothesis that reactive oxygen species (ROS) induced DNA damage can promote sexual recombination in eukaryotes which might have been a decisive factor for the origin of sex. The fact that some recombination enzymes also participate in meiotic sex in modern eukaryotes reinforces the idea that sexual reproduction emerged as consequence of specific mechanisms to cope with mutations and alterations in genetic material. In this review we will discuss about origin of sex and different strategies of evolve sexual reproduction in some protists such that cause human diseases like malaria, toxoplasmosis, sleeping sickness, Chagas disease, and leishmaniasis.
DOI: 10.6084/m9.figshare.21310323.v1
title: Sex in protists: A new perspective on the reproduction mechanisms of trypanosomatids

description: Abstract The Protist kingdom individuals are the most ancestral representatives of eukaryotes. They have inhabited Earth since ancient times and are currently found in the most diverse environments presenting a great heterogeneity of life forms. The unicellular and multicellular algae, photosynthetic and heterotrophic organisms, as well as free-living and pathogenic protozoa represents the protist group. The evolution of sex is directly associated with the origin of eukaryotes being protists the earliest protagonists of sexual reproduction on earth. In eukaryotes, the recombination through genetic exchange is a ubiquitous mechanism that can be stimulated by DNA damage. Scientific evidences support the hypothesis that reactive oxygen species (ROS) induced DNA damage can promote sexual recombination in eukaryotes which might have been a decisive factor for the origin of sex. The fact that some recombination enzymes also participate in meiotic sex in modern eukaryotes reinforces the idea that sexual reproduction emerged as consequence of specific mechanisms to cope with mutations and alterations in genetic material. In this review we will discuss about origin of sex and different strategies of evolve sexual reproduction in some protists such that cause human diseases like malaria, toxoplasmosis, sleeping sickness, Chagas disease, and leishmaniasis.
DOI: 10.6084/m9.figshare.21310324
title: Hospitalizations and adverse drug events in the Brazilian unified health system: a ten-year retrospective analysis of routine data

description: ABSTRACT OBJECTIVE To describe the frequency and characteristics of hospitalizations for/with adverse drug events in the Brazilian unified health system routine data. METHODS Nationwide retrospective study using data obtained from a period of ten years from the Brazil Hospital Information System (SIH-SUS), an administrative database that registers hospitalizations in the unified health system. We selected hospitalizations with primary and/or secondary diagnosis related to adverse drug events according to a list of validated International Classification Disease 10th edition (ICD-10) codes. These events were described according to year, age group, sex, length of hospital stay, mortality, hospital costs, Brazilian geographical region, and category of ICD-10 codes. Crude hospitalization rates of adverse drug events per 100,000 inhabitants were obtained and Joinpoint Regression was used to analyze temporal changes in these rates along the years. The most frequent ICD-10 codes were also identified. RESULTS Over ten years, 603,663 hospitalizations in Brazil were found in the database, out of which 2.5% of the patients died. Though 2009 had the highest prevalence of hospitalization per 100,000 inhabitants (32.57), no significant annual change in rates was found for the entire period. All age groups and sexes presented a jointpoint in temporal series; however, only women had a significative increase trend. The most frequent codes were from the chapter of mental and behavioral disorders (F19.2, F19.0, and F19.5 codes). CONCLUSIONS The database methodology can be useful to estimate frequencies of adverse drug events and perform characterization nationwide and to help monitor morbidity along the years.
DOI: 10.6084/m9.figshare.21310324.v1
title: Hospitalizations and adverse drug events in the Brazilian unified health system: a ten-year retrospective analysis of routine data

description: ABSTRACT OBJECTIVE To describe the frequency and characteristics of hospitalizations for/with adverse drug events in the Brazilian unified health system routine data. METHODS Nationwide retrospective study using data obtained from a period of ten years from the Brazil Hospital Information System (SIH-SUS), an administrative database that registers hospitalizations in the unified health system. We selected hospitalizations with primary and/or secondary diagnosis related to adverse drug events according to a list of validated International Classification Disease 10th edition (ICD-10) codes. These events were described according to year, age group, sex, length of hospital stay, mortality, hospital costs, Brazilian geographical region, and category of ICD-10 codes. Crude hospitalization rates of adverse drug events per 100,000 inhabitants were obtained and Joinpoint Regression was used to analyze temporal changes in these rates along the years. The most frequent ICD-10 codes were also identified. RESULTS Over ten years, 603,663 hospitalizations in Brazil were found in the database, out of which 2.5% of the patients died. Though 2009 had the highest prevalence of hospitalization per 100,000 inhabitants (32.57), no significant annual change in rates was found for the entire period. All age groups and sexes presented a jointpoint in temporal series; however, only women had a significative increase trend. The most frequent codes were from the chapter of mental and behavioral disorders (F19.2, F19.0, and F19.5 codes). CONCLUSIONS The database methodology can be useful to estimate frequencies of adverse drug events and perform characterization nationwide and to help monitor morbidity along the years.
DOI: 10.6084/m9.figshare.21310327
title: Religiosity is associated with caregivers’ perception of preschool children’s dental health

description: Abstract The aim of the study was to investigate the association between psychosocial factors and perception of caregivers about the dental health of their preschool children. A cross-sectional analysis was performed with 146 caregiver-child dyads attended at Pediatric Dentistry school clinics in Goiânia, Midwest Brazil. Data were collected through a structured interview and a questionnaire with the caregivers and the children’s dental records. The study outcome was caregivers’ perception of children’s dental health (positive or negative). The independent psychosocial variables were religiosity (Duke University Religion Index - DUREL) and Sense of Coherence (Antonovsky’s SOC-13 scale). Sociodemographic data and oral health-related variables were also collected as covariates. Bivariate analysis (Pearson’s chi-square, T-test, and Mann-Whitney) and Poisson regression with robust variance were performed. The prevalence of negative perception was 54.8%. In bivariate analysis, negative perception was associated with caries experience and report of dental pain at any time in the child’s life. In the adjusted regression model, prevalence of caregivers with negative perception of their children’s dental health was 1.38 times higher in the group with low organizational religiosity (PR = 1.38; 95%CI 1.05–1.81) and 2.35 times higher in the group of children with high caries experience (PR = 2.35; 95%CI 1.54–3.60). In conclusion, religiosity was associated with caregivers’ perception of dental health of their preschool children undergoing treatment in specialized dental clinics, regardless of their caries experience.
DOI: 10.6084/m9.figshare.21310327.v1
title: Religiosity is associated with caregivers’ perception of preschool children’s dental health

description: Abstract The aim of the study was to investigate the association between psychosocial factors and perception of caregivers about the dental health of their preschool children. A cross-sectional analysis was performed with 146 caregiver-child dyads attended at Pediatric Dentistry school clinics in Goiânia, Midwest Brazil. Data were collected through a structured interview and a questionnaire with the caregivers and the children’s dental records. The study outcome was caregivers’ perception of children’s dental health (positive or negative). The independent psychosocial variables were religiosity (Duke University Religion Index - DUREL) and Sense of Coherence (Antonovsky’s SOC-13 scale). Sociodemographic data and oral health-related variables were also collected as covariates. Bivariate analysis (Pearson’s chi-square, T-test, and Mann-Whitney) and Poisson regression with robust variance were performed. The prevalence of negative perception was 54.8%. In bivariate analysis, negative perception was associated with caries experience and report of dental pain at any time in the child’s life. In the adjusted regression model, prevalence of caregivers with negative perception of their children’s dental health was 1.38 times higher in the group with low organizational religiosity (PR = 1.38; 95%CI 1.05–1.81) and 2.35 times higher in the group of children with high caries experience (PR = 2.35; 95%CI 1.54–3.60). In conclusion, religiosity was associated with caregivers’ perception of dental health of their preschool children undergoing treatment in specialized dental clinics, regardless of their caries experience.
DOI: 10.6084/m9.figshare.21310326
title: L-lysine and dietary fiber improve the physicochemical properties of sausage without added phosphate and reduced salt levels

description: ABSTRACT The demand for clean label foods has driven research in the meat product sector. The objective of this study was to evaluate the effect on the physicochemical properties of adding L-lysine, wheat fiber (WTF) and microcrystalline cellulose (MCC) in sausage without the addition of sodium tripolyphosphate (STPP) and with reduced salt levels. Eight treatments were produced in total. Three control treatments were: CON1 - 0.5 % sodium tripolyphosphate and 2 % salt; CON2 - without STPP and 2 % salt; CON3 - without STPP and 1 % salt. Five other treatments were carried out without STPP and 1 % of salt: LYS - 0.8 % L-lysine; WTF - 2 % wheat fiber; MCC - 2 % microcrystalline cellulose fiber; LYSWTF - 0.8 % L-lysine and 2 % wheat fiber; LYSMCC - 0.8 % L-lysine and 2 % microcrystalline cellulose fiber. L-lysine and wheat fiber provided good emulsion stability for sausages. L-lysine and MCC increased the yield of the products. Microcrystalline cellulose increased the red color value (a*) of sausages. The intensity of the yellow color value (b*) was significantly affected by the removal of STPP and the reduction of salt levels, but L-lysine and MCC improved this parameter, providing similar results to CON1. Adding of L-lysine and dietary fiber increased hardness in sausages without added STPP and with salt reduction. L-lysine and wheat fiber are promising for reformulating emulsified meat product without phosphate added and with reduced salt levels due to lipid oxidation control and improvement in emulsion stability.
DOI: 10.6084/m9.figshare.21310326.v1
title: L-lysine and dietary fiber improve the physicochemical properties of sausage without added phosphate and reduced salt levels

description: ABSTRACT The demand for clean label foods has driven research in the meat product sector. The objective of this study was to evaluate the effect on the physicochemical properties of adding L-lysine, wheat fiber (WTF) and microcrystalline cellulose (MCC) in sausage without the addition of sodium tripolyphosphate (STPP) and with reduced salt levels. Eight treatments were produced in total. Three control treatments were: CON1 - 0.5 % sodium tripolyphosphate and 2 % salt; CON2 - without STPP and 2 % salt; CON3 - without STPP and 1 % salt. Five other treatments were carried out without STPP and 1 % of salt: LYS - 0.8 % L-lysine; WTF - 2 % wheat fiber; MCC - 2 % microcrystalline cellulose fiber; LYSWTF - 0.8 % L-lysine and 2 % wheat fiber; LYSMCC - 0.8 % L-lysine and 2 % microcrystalline cellulose fiber. L-lysine and wheat fiber provided good emulsion stability for sausages. L-lysine and MCC increased the yield of the products. Microcrystalline cellulose increased the red color value (a*) of sausages. The intensity of the yellow color value (b*) was significantly affected by the removal of STPP and the reduction of salt levels, but L-lysine and MCC improved this parameter, providing similar results to CON1. Adding of L-lysine and dietary fiber increased hardness in sausages without added STPP and with salt reduction. L-lysine and wheat fiber are promising for reformulating emulsified meat product without phosphate added and with reduced salt levels due to lipid oxidation control and improvement in emulsion stability.
DOI: 10.6084/m9.figshare.21310329
title: Are salivary flow rates associated with histopathologic aspects in patients with rheumatoid arthritis?

description: Abstract The aim of this retrospective cross-sectional study was to verify the association between salivary flow rates (SFR) and the histopathologic aspects of labial salivary glands (LSG) in patients with rheumatoid arthritis (RA). Patients presenting rheumatologic diseases referred for oral evaluation were included in the study if they had RA and had SFR measured and LSG biopsy performed. Patients were excluded if they had systemic conditions that affect SFR or if they were being treated for hyposalivation. Cases without enough material for histopathologic analysis were also excluded. Data were collected through questionnaires, oral examination, resting and stimulated SFR, and LSG biopsies. A histopathologic reevaluation was carried out in order to seek for additional histopathologic aspects. Fifty-one patients met the inclusion criteria. The mean age was 53.5 years (25–77), and 94.1% were women. The median resting and stimulated SFRs were 0.24 mL/min and 1.02 mL/min, respectively. The presence of lymphocytic focus and fibrosis were significantly associated with stimulated SFR, but not with resting SFR. The odds ratio of patients who had hyposalivation for presenting a positive lymphocytic focus was 7.33 (confidence interval CI: 1.53–35.23) by the stimulated technique, and 2.56 (CI: 0.57–11.40) in resting SFR. In the medical records, 14 (31.80%) patients had been diagnosed with secondary Sjögren’s syndrome. In conclusion, stimulated SFR represent a good screening test to predict lymphocytic focus in LSG in patients with RA, which represents the most specific test to diagnose Sjögren’s syndrome.
DOI: 10.6084/m9.figshare.21310329.v1
title: Are salivary flow rates associated with histopathologic aspects in patients with rheumatoid arthritis?

description: Abstract The aim of this retrospective cross-sectional study was to verify the association between salivary flow rates (SFR) and the histopathologic aspects of labial salivary glands (LSG) in patients with rheumatoid arthritis (RA). Patients presenting rheumatologic diseases referred for oral evaluation were included in the study if they had RA and had SFR measured and LSG biopsy performed. Patients were excluded if they had systemic conditions that affect SFR or if they were being treated for hyposalivation. Cases without enough material for histopathologic analysis were also excluded. Data were collected through questionnaires, oral examination, resting and stimulated SFR, and LSG biopsies. A histopathologic reevaluation was carried out in order to seek for additional histopathologic aspects. Fifty-one patients met the inclusion criteria. The mean age was 53.5 years (25–77), and 94.1% were women. The median resting and stimulated SFRs were 0.24 mL/min and 1.02 mL/min, respectively. The presence of lymphocytic focus and fibrosis were significantly associated with stimulated SFR, but not with resting SFR. The odds ratio of patients who had hyposalivation for presenting a positive lymphocytic focus was 7.33 (confidence interval CI: 1.53–35.23) by the stimulated technique, and 2.56 (CI: 0.57–11.40) in resting SFR. In the medical records, 14 (31.80%) patients had been diagnosed with secondary Sjögren’s syndrome. In conclusion, stimulated SFR represent a good screening test to predict lymphocytic focus in LSG in patients with RA, which represents the most specific test to diagnose Sjögren’s syndrome.