cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.20018033.v1
title: Gene expression evaluation of antioxidant enzymes in patients with hepatocellular carcinoma: RT-qPCR and bioinformatic analyses

description: Abstract Any condition leading to chronic liver disease is a potential oncogenic agent for hepatocellular carcinoma (HCC). Alterations in the expression of antioxidant enzymes could alter the redox balance. Our aim was to evaluate the expression of the genes GPX1, GPX4, SEP15, SELENOP, SOD1, SOD2, GSR, CAT, and NFE2L2 in patients with HCC. Differential gene expression analysis was performed using RNA-Seq data from the TCGA and GTEx databases, and RT-qPCR data from HCC patient samples. Bioinformatic analysis revealed significant differential expression in most genes. GPX4 expression was significantly increased (p=0.02), while SOD2 expression was significantly decreased (p=0.04) in experimental data. In TCGA samples, alpha-fetoprotein levels (mg/dL) were negatively correlated with the expression of SEP15 (p&lt;0.001), SELENOP (p&lt;0.001), SOD1 (p&lt;0.001), SOD2 (p&lt;0.001), CAT (p&lt;0.001), and NFE2L2 (p=0.004). Alpha-fetoprotein levels were positively correlated with the expression of GPX4 (p=0.02) and SELENOP (p=0.01) in the experimental data. Low expression of GPX1 (p=0.006), GPX4 (p=0.01), SELENOP (p=0.006), SOD1 (p=0.007), CAT (p&lt;0.001), and NFE2L2 (p&lt;0.001), and higher levels of GSR, were associated with low overall survival at 12 months. These results suggest a significant role for these antioxidant enzymes in HCC pathogenesis and severity.
DOI: 10.6084/m9.figshare.20018033
title: Gene expression evaluation of antioxidant enzymes in patients with hepatocellular carcinoma: RT-qPCR and bioinformatic analyses

description: Abstract Any condition leading to chronic liver disease is a potential oncogenic agent for hepatocellular carcinoma (HCC). Alterations in the expression of antioxidant enzymes could alter the redox balance. Our aim was to evaluate the expression of the genes GPX1, GPX4, SEP15, SELENOP, SOD1, SOD2, GSR, CAT, and NFE2L2 in patients with HCC. Differential gene expression analysis was performed using RNA-Seq data from the TCGA and GTEx databases, and RT-qPCR data from HCC patient samples. Bioinformatic analysis revealed significant differential expression in most genes. GPX4 expression was significantly increased (p=0.02), while SOD2 expression was significantly decreased (p=0.04) in experimental data. In TCGA samples, alpha-fetoprotein levels (mg/dL) were negatively correlated with the expression of SEP15 (p&lt;0.001), SELENOP (p&lt;0.001), SOD1 (p&lt;0.001), SOD2 (p&lt;0.001), CAT (p&lt;0.001), and NFE2L2 (p=0.004). Alpha-fetoprotein levels were positively correlated with the expression of GPX4 (p=0.02) and SELENOP (p=0.01) in the experimental data. Low expression of GPX1 (p=0.006), GPX4 (p=0.01), SELENOP (p=0.006), SOD1 (p=0.007), CAT (p&lt;0.001), and NFE2L2 (p&lt;0.001), and higher levels of GSR, were associated with low overall survival at 12 months. These results suggest a significant role for these antioxidant enzymes in HCC pathogenesis and severity.
DOI: 10.6084/m9.figshare.20018037
title: Blood groups in Native Americans: a look beyond ABO and Rh

description: Abstract The study presents comparisons between blood group frequencies beyond ABO and Rh blood systems in Native American populations and previously published data from Brazilian blood donors. The frequencies of Diego (c.2561C&gt;T, rs2285644), Kell (c.578C&gt;T, rs8176058), Duffy (c.125A&gt;G, rs12075, c.1−67T&gt;C, rs2814778) and Kidd (c.838A&gt;G, rs1058396) variants in Kaingang (n=72) and Guarani (n=234) populations from Brazil (1990-2000) were obtained and compared with data from these populations sampled during the 1960s and with individuals of different Brazilian regions. Data showed high frequencies of DI*01 and FY*01 alleles: 11.8% and 57.6% in Kaingang and 6.8% and 75.7% in Guarani groups, respectively. The main results indicated: (1) reduction in genetic distance over time of Kaingang and Guarani in relation to other Brazilian populations is suggestive of ongoing admixture; (2) significant differences in some frequencies of blood group markers (especially Diego, Kidd and Duffy) in relation to Native Americans and individuals from different geographical regions of Brazil. Our study shows that the frequency of red blood cell polymorphisms in two Native American groups is very different from that of blood donors, when we evaluated blood groups different from ABO and Rh systems, suggesting that a better ethnic characterization of blood unit receptors is necessary.
DOI: 10.6084/m9.figshare.20018037.v1
title: Blood groups in Native Americans: a look beyond ABO and Rh

description: Abstract The study presents comparisons between blood group frequencies beyond ABO and Rh blood systems in Native American populations and previously published data from Brazilian blood donors. The frequencies of Diego (c.2561C&gt;T, rs2285644), Kell (c.578C&gt;T, rs8176058), Duffy (c.125A&gt;G, rs12075, c.1−67T&gt;C, rs2814778) and Kidd (c.838A&gt;G, rs1058396) variants in Kaingang (n=72) and Guarani (n=234) populations from Brazil (1990-2000) were obtained and compared with data from these populations sampled during the 1960s and with individuals of different Brazilian regions. Data showed high frequencies of DI*01 and FY*01 alleles: 11.8% and 57.6% in Kaingang and 6.8% and 75.7% in Guarani groups, respectively. The main results indicated: (1) reduction in genetic distance over time of Kaingang and Guarani in relation to other Brazilian populations is suggestive of ongoing admixture; (2) significant differences in some frequencies of blood group markers (especially Diego, Kidd and Duffy) in relation to Native Americans and individuals from different geographical regions of Brazil. Our study shows that the frequency of red blood cell polymorphisms in two Native American groups is very different from that of blood donors, when we evaluated blood groups different from ABO and Rh systems, suggesting that a better ethnic characterization of blood unit receptors is necessary.
DOI: 10.6084/m9.figshare.20018039
title: Structural analysis of new compound heterozygous variants in PEPD gene identified in a patient with Prolidase Deficiency diagnosed by exome sequencing

description: Abstract Prolidase Deficiency (PD) is an autosomal recessive rare disorder caused by loss or reduction of prolidase enzymatic activity due to variants in the PEPD gene. PD clinical features vary among affected individuals: skin ulcerations, recurrent infections, and developmental delay are common. In this study, we describe a 16-year-old boy with a mild PD phenotype comprising chronic eczema, recurrent infections and elevated IgE. Whole exome sequencing analysis revealed three PEPD variants: c.575T&gt;C p.(Leu192Pro) inherited from the mother, and c.692_694del p.(Tyr231del) and c.1409G&gt;A p.(Arg470His), both inherited from the father. The variant p.(Tyr231del) has been previously characterized by high-resolution X-ray structure analysis as altering protein dynamics/flexibility. In order to study the effects of the other two prolidase variants, we performed site directed mutagenesis purification and crystallization studies. A high-resolution X-ray structure could only be obtained for the p.(Arg470His) variant, which showed no significant structural differences in comparison to WT prolidase. On the other hand, the p.(Leu192Pro) variant led to significant protein destabilization. Hence, we conclude that the maternal p.(Leu192Pro) variant was likely causally associated with the proband´s disease, together with the known pathogenic paternal variant p.(Tyr231del). Our results demonstrated the utility of exome sequencing to perform diagnosis in PD cases with mild phenotype.
DOI: 10.6084/m9.figshare.20018039.v1
title: Structural analysis of new compound heterozygous variants in PEPD gene identified in a patient with Prolidase Deficiency diagnosed by exome sequencing

description: Abstract Prolidase Deficiency (PD) is an autosomal recessive rare disorder caused by loss or reduction of prolidase enzymatic activity due to variants in the PEPD gene. PD clinical features vary among affected individuals: skin ulcerations, recurrent infections, and developmental delay are common. In this study, we describe a 16-year-old boy with a mild PD phenotype comprising chronic eczema, recurrent infections and elevated IgE. Whole exome sequencing analysis revealed three PEPD variants: c.575T&gt;C p.(Leu192Pro) inherited from the mother, and c.692_694del p.(Tyr231del) and c.1409G&gt;A p.(Arg470His), both inherited from the father. The variant p.(Tyr231del) has been previously characterized by high-resolution X-ray structure analysis as altering protein dynamics/flexibility. In order to study the effects of the other two prolidase variants, we performed site directed mutagenesis purification and crystallization studies. A high-resolution X-ray structure could only be obtained for the p.(Arg470His) variant, which showed no significant structural differences in comparison to WT prolidase. On the other hand, the p.(Leu192Pro) variant led to significant protein destabilization. Hence, we conclude that the maternal p.(Leu192Pro) variant was likely causally associated with the proband´s disease, together with the known pathogenic paternal variant p.(Tyr231del). Our results demonstrated the utility of exome sequencing to perform diagnosis in PD cases with mild phenotype.
DOI: 10.6084/m9.figshare.20018045.v1
title: Increased prevalence of the CVD-associated ANRIL allele in the Roma/Gypsy population in comparison with the majority Czech population

description: Abstract Cardiovascular disease (CVD) is a major cause of death around the world, with highest prevalence reported in minority Roma/Gypsy populations living in developed countries. Whether these differences are caused by unhealthy lifestyles or genetic factors remain unknown. The aim of our study was to examine the genotype frequencies of the rs10757274 polymorphism in the 9p.21 locus within ANRIL (antisense non-coding RNA in the INK4 locus), a long non-coding RNA located in the vicinity of the CDKN2A/2B inhibitors loci. ANRIL is understood to be the strongest genetic determinant of CVD in Caucasians. Using PCR-RFLP, we analysed the ANRIL rs10757274 polymorphism in 298 non-Roma (50% male) and 302 Roma/Gypsy (50% male) adult (39.5 ± 15.1 years and 39.2 ± 12.8 years, respectively) subjects. We found that frequencies of the ANRIL GG, GA and AA genotypes were 20.1%, 52.4% and 27.5% in the majority population and 32.9%, 47.9% and 19.2% in Roma/Gypsy subjects, respectively. The distribution of genotypes was deemed significantly different at P &lt; 0.001. Within the Roma/Gypsy population, we detected increased prevalence of the CVD-associated GG genotype. Increased prevalence of CVD among Roma/Gypsies subjects may be significantly linked to genetic background.
DOI: 10.6084/m9.figshare.20018045
title: Increased prevalence of the CVD-associated ANRIL allele in the Roma/Gypsy population in comparison with the majority Czech population

description: Abstract Cardiovascular disease (CVD) is a major cause of death around the world, with highest prevalence reported in minority Roma/Gypsy populations living in developed countries. Whether these differences are caused by unhealthy lifestyles or genetic factors remain unknown. The aim of our study was to examine the genotype frequencies of the rs10757274 polymorphism in the 9p.21 locus within ANRIL (antisense non-coding RNA in the INK4 locus), a long non-coding RNA located in the vicinity of the CDKN2A/2B inhibitors loci. ANRIL is understood to be the strongest genetic determinant of CVD in Caucasians. Using PCR-RFLP, we analysed the ANRIL rs10757274 polymorphism in 298 non-Roma (50% male) and 302 Roma/Gypsy (50% male) adult (39.5 ± 15.1 years and 39.2 ± 12.8 years, respectively) subjects. We found that frequencies of the ANRIL GG, GA and AA genotypes were 20.1%, 52.4% and 27.5% in the majority population and 32.9%, 47.9% and 19.2% in Roma/Gypsy subjects, respectively. The distribution of genotypes was deemed significantly different at P &lt; 0.001. Within the Roma/Gypsy population, we detected increased prevalence of the CVD-associated GG genotype. Increased prevalence of CVD among Roma/Gypsies subjects may be significantly linked to genetic background.
DOI: 10.6084/m9.figshare.20018052
title: Association of TYK2 polymorphisms with autoimmune diseases: A comprehensive and updated systematic review with meta-analysis

description: Abstract Autoimmune diseases are characterized by the loss of self-tolerance, leading to immune-mediated tissue destruction and chronic inflammation. Tyrosine kinase 2 (TYK2) protein plays a key role in immunity and apoptosis pathways. Studies have reported associations between single nucleotide polymorphisms (SNPs) in the TYK2 gene and autoimmune diseases; however, results are still inconclusive. Thus, we conducted a systematic review followed by meta-analysis. A literature search was performed to find studies that investigated associations between TYK2 SNPs and autoimmune diseases (multiple sclerosis, systemic lupus erythematosus, Crohn’s disease, ulcerative colitis, psoriasis, rheumatoid arthritis, type 1 diabetes, and inflammatory bowel disease). Pooled odds ratios (OR) with 95 % CI were calculated using random (REM) or fixed (FEM) effects models in the Stata 11.0 Software. Thirty-four articles were eligible for inclusion in the meta-analyses, comprising 9 different SNPs: rs280496, rs280500, rs280523, rs280519, rs2304256, rs12720270, rs12720356, rs34536443, and rs35018800. Meta-analysis results showed the minor alleles of rs2304256, rs12720270, rs12720356, rs34536443, and rs35018800 SNPs were associated with protection against autoimmune diseases. Moreover, the A allele of the rs280519 SNP was associated with risk for systemic lupus erythematosus. Our meta-analyses demonstrated that the rs2304256, rs12720270, rs12720356, rs34536443, rs35018800, and rs280519 SNPs in the TYK2 gene are associated with different autoimmune diseases.
DOI: 10.6084/m9.figshare.20018052.v1
title: Association of TYK2 polymorphisms with autoimmune diseases: A comprehensive and updated systematic review with meta-analysis

description: Abstract Autoimmune diseases are characterized by the loss of self-tolerance, leading to immune-mediated tissue destruction and chronic inflammation. Tyrosine kinase 2 (TYK2) protein plays a key role in immunity and apoptosis pathways. Studies have reported associations between single nucleotide polymorphisms (SNPs) in the TYK2 gene and autoimmune diseases; however, results are still inconclusive. Thus, we conducted a systematic review followed by meta-analysis. A literature search was performed to find studies that investigated associations between TYK2 SNPs and autoimmune diseases (multiple sclerosis, systemic lupus erythematosus, Crohn’s disease, ulcerative colitis, psoriasis, rheumatoid arthritis, type 1 diabetes, and inflammatory bowel disease). Pooled odds ratios (OR) with 95 % CI were calculated using random (REM) or fixed (FEM) effects models in the Stata 11.0 Software. Thirty-four articles were eligible for inclusion in the meta-analyses, comprising 9 different SNPs: rs280496, rs280500, rs280523, rs280519, rs2304256, rs12720270, rs12720356, rs34536443, and rs35018800. Meta-analysis results showed the minor alleles of rs2304256, rs12720270, rs12720356, rs34536443, and rs35018800 SNPs were associated with protection against autoimmune diseases. Moreover, the A allele of the rs280519 SNP was associated with risk for systemic lupus erythematosus. Our meta-analyses demonstrated that the rs2304256, rs12720270, rs12720356, rs34536443, rs35018800, and rs280519 SNPs in the TYK2 gene are associated with different autoimmune diseases.
DOI: 10.6084/m9.figshare.20018057.v1
title: The fructose-1,6-bisphosphatase deficiency and the p.(Lys204ArgfsTer72) variant

description: Abstract Fructose-1,6-bisphosphatase (FBPase) deficiency is a rare inborn error of fructose metabolism caused by pathogenic variants in the FBP1 gene. As gluconeogenesis is affected, catabolic episodes can induce ketotic hypoglycemia in patients. FBP1 analysis is the most commonly used approach for the diagnosis of this disorder. Herein, a Brazilian patient is reported. The proband, a girl born to a consanguineous couple, presented with severe hypoglycemia crisis in the neonatal period. At the age 17 months, presented a new crisis accompanied by metabolic acidosis associated with a feverish episode. Genetic analysis was performed by next-generation sequencing (NGS), identifying the NM_000507.3:c.611_614del variant in homozygosis in the FBP1 gene. In silico analysis and 3D modeling were performed, suggesting that this variant is associated with a loss of sites for substrate and Mg2+ binding and for posttranslational modifications of FBPase. The c.611_614del variant is located in a repetitive region of the FBP1 gene that appears to be a hotspot for mutational events. This frameshift creates a premature termination codon in the last coding exon which escapes the nonsense-mediated decay mechanism, according to in silico analysis. This variant results in an intrinsically disordered protein with loss of substrate recognition and post-translational modification sites.
DOI: 10.6084/m9.figshare.20018057
title: The fructose-1,6-bisphosphatase deficiency and the p.(Lys204ArgfsTer72) variant

description: Abstract Fructose-1,6-bisphosphatase (FBPase) deficiency is a rare inborn error of fructose metabolism caused by pathogenic variants in the FBP1 gene. As gluconeogenesis is affected, catabolic episodes can induce ketotic hypoglycemia in patients. FBP1 analysis is the most commonly used approach for the diagnosis of this disorder. Herein, a Brazilian patient is reported. The proband, a girl born to a consanguineous couple, presented with severe hypoglycemia crisis in the neonatal period. At the age 17 months, presented a new crisis accompanied by metabolic acidosis associated with a feverish episode. Genetic analysis was performed by next-generation sequencing (NGS), identifying the NM_000507.3:c.611_614del variant in homozygosis in the FBP1 gene. In silico analysis and 3D modeling were performed, suggesting that this variant is associated with a loss of sites for substrate and Mg2+ binding and for posttranslational modifications of FBPase. The c.611_614del variant is located in a repetitive region of the FBP1 gene that appears to be a hotspot for mutational events. This frameshift creates a premature termination codon in the last coding exon which escapes the nonsense-mediated decay mechanism, according to in silico analysis. This variant results in an intrinsically disordered protein with loss of substrate recognition and post-translational modification sites.
DOI: 10.5287/bodleian:nom6ygbbz
title: Research data - deformation behaviour of ion-irradiated FeCr: a nanoindentation study
DOI: 10.6084/m9.figshare.20018064
title: Genetic information improves the prediction of major adverse cardiovascular events in the GENEMACOR population

description: Abstract The inclusion of a genetic risk score (GRS) can modify the risk prediction of coronary artery disease (CAD), providing an advantage over the use of traditional models. The predictive value of the genetic information on the recurrence of major adverse cardiovascular events (MACE) remains controversial. A total of 33 genetic variants previously associated with CAD were genotyped in 1587 CAD patients from the GENEMACOR study. Of these, 18 variants presented an hazard ratio &gt;1, so they were selected to construct a weighted GRS (wGRS). MACE discrimination and reclassiﬁcation were evaluated by C-Statistic, Net Reclassification Index and Integrated Discrimination Improvement methodologies. After the addition of wGRS to traditional predictors, the C-index increased from 0.566 to 0.572 (p=0.0003). Subsequently, adding wGRS to traditional plus clinical risk factors, this model slightly improved from 0.620 to 0.622 but with statistical significance (p=0.004). NRI showed that 17.9% of the cohort was better reclassified when the primary model was associated with wGRS. The Kaplan-Meier estimator showed that, at 15-year follow-up, the group with a higher number of risk alleles had a significantly higher MACE occurrence (p=0.011). In CAD patients, wGRS improved MACE risk prediction, discrimination and reclassification over the conventional factors, providing better cost-effective therapeutic strategies.
DOI: 10.6084/m9.figshare.20018064.v1
title: Genetic information improves the prediction of major adverse cardiovascular events in the GENEMACOR population

description: Abstract The inclusion of a genetic risk score (GRS) can modify the risk prediction of coronary artery disease (CAD), providing an advantage over the use of traditional models. The predictive value of the genetic information on the recurrence of major adverse cardiovascular events (MACE) remains controversial. A total of 33 genetic variants previously associated with CAD were genotyped in 1587 CAD patients from the GENEMACOR study. Of these, 18 variants presented an hazard ratio &gt;1, so they were selected to construct a weighted GRS (wGRS). MACE discrimination and reclassiﬁcation were evaluated by C-Statistic, Net Reclassification Index and Integrated Discrimination Improvement methodologies. After the addition of wGRS to traditional predictors, the C-index increased from 0.566 to 0.572 (p=0.0003). Subsequently, adding wGRS to traditional plus clinical risk factors, this model slightly improved from 0.620 to 0.622 but with statistical significance (p=0.004). NRI showed that 17.9% of the cohort was better reclassified when the primary model was associated with wGRS. The Kaplan-Meier estimator showed that, at 15-year follow-up, the group with a higher number of risk alleles had a significantly higher MACE occurrence (p=0.011). In CAD patients, wGRS improved MACE risk prediction, discrimination and reclassification over the conventional factors, providing better cost-effective therapeutic strategies.
DOI: 10.6084/m9.figshare.20018066
title: Establishment of rapid and non-invasive protocols to identify B-carrying individuals of Psalidodon paranae

description: Abstract Supernumerary, or B, chromosomes are present in several eukaryotes, including characid fish of the genus Psalidodon. Notably, Psalidodon paranae carries the most studied B chromosome variant, a macro-B chromosome. The origin of this element was determined to be an isochromosome; however, data regarding its inheritance remain unavailable due to methodological barriers such as the lack of an efficient, non-invasive, and rapid protocol for identifying B-carrying individuals that would enable the design of efficient crossing experiments. Thus, in this study, we primarily aimed was to develop two non-invasive and fast (approximately 2 h) methods to identify the presence of B chromosomes in live specimens of P. paranae based on satellite DNA (satDNA) sequences known to be present in this element. The methods include fluorescence in situ hybridization in interphase nuclei and relative gene quantification of satDNAs using quantitative polymerase chain reaction. Our results reveal the efficiency of quick-fluorescence in situ hybridization and quantitative polymerase chain reaction for identifying B-carrying individuals using the proposed satDNA sequences and open up new possibilities to study B chromosomes.