cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.4570207.v1
title: Potential Epigenetic Biomarkers of Obesity Related Insulin Resistance in Human Whole-blood

description: Obesity can increase the risk of complex metabolic diseases, including insulin resistance. Moreover, obesity can be caused by environmental and genetic factors. However, the epigenetic mechanisms of obesity are not well defined. Therefore, the identification of novel epigenetic biomarkers of obesity allows for a more complete understanding of the disease and its underlying insulin resistance. The aim of our study was to identify DNA methylation changes in whole-blood that were strongly associated with obesity and insulin resistance. Whole-blood was obtained from lean (n = 10; BMI = 23.6 ± 0.7 kg/m<sup>2</sup>) and obese (n = 10; BMI = 34.4 ± 1.3 kg/m<sup>2</sup>) participants in combination with euglycemic hyperinsulinemic clamps to assess insulin sensitivity. We performed reduced representation bisulfite sequencing on genomic DNA isolated from the blood. We identified 49 differentially methylated cytosines (DMCs; q&lt;0.05) that were altered in obese compared to lean participants. We identified two sites (Chr.21:46,957,981 and Chr.21:46,957,915) in the 5′ untranslated region of solute carrier family 19 member 1 (<i>SLC19A1</i>) with decreased in methylation in obese participants (lean 0.73 ± 0.11 vs. obese 0.09 ± 0.05; lean 0.68 ± 0.10 vs. obese 0.09 ± 0.05, respectively). These two DMCs identified by obesity were also significantly predicted by insulin sensitivity (r = 0.68, <i>P</i> = 0.003; r = 0.66; <i>P</i> = 0.004). In addition, we performed a differentially methylated region (DMR) analysis and demonstrated a decrease in methylation of Chr.21:46,957,915–46,958,001 in <i>SLC19A1</i> of −34.9% (70.4% lean vs. 35.5% obese). The decrease in whole-blood <i>SLC19A1</i> methylation in our obese participants was similar to the change observed in skeletal muscle (Chr.21:46,957,981, lean 0.70 ± 0.09 vs. obese 0.31 ± 0.11 and Chr.21:46,957,915, lean 0.72 ± 0.11 vs. obese 0.31 ± 0.13). Pyrosequencing analysis further demonstrated a decrease in methylation at Chr.21:46,957,915 in both whole-blood (lean 0.71 ± 0.10 vs. obese 0.18 ± 0.06) and skeletal muscle (lean 0.71 ± 0.10 vs. obese 0.30 ± 0.11). Our findings demonstrate a new potential epigenetic biomarker, <i>SLC19A1</i>, for obesity and its underlying insulin resistance.
DOI: 10.6084/m9.figshare.4570060
title: Supplementary Material for: Dynamic Amygdala Influences on the Fronto-Striatal Brain Mechanisms Involved in Self-Control of Impulsive Desires

description: Human decisions are guided by a variety of motivational factors, such as immediate rewards, long-term goals, and emotions. We used functional magnetic resonance imaging to investigate the dynamic functional interactions between the amygdala, the nucleus accumbens, and the prefrontal cortex that underlie the influences of emotions, desires, and rationality on human decisions. We found that increased functional connectivity between the amygdala and the nucleus accumbens facilitated the approach of an immediate reward in the presence of emotional information. Further, increased functional interactions of the anteroventral prefrontal cortex with the amygdala and the nucleus accumbens were associated with rational decisions in dilemma situations. These findings support previous animal studies by demonstrating that emotional signals from the amygdala and goal-oriented information from prefrontal cortices interface in the nucleus accumbens to guide human decisions and reward-directed actions.
DOI: 10.6084/m9.figshare.4570063
title: Supplementary Material for: Decline in Asthma Prevalence and Severity in Israel over a 10-Year Period

description: <b><i>Background:</i></b> The prevalence of asthma has increased in western countries towards the end of the last century, but recently seems to have stabilized. <b><i>Objective:</i></b> To evaluate trends in the prevalence and severity of asthma that occurred in Israel over the past decade. <b><i>Methods:</i></b> The medical records of 17-year-old boys, eligible for national service, between 1999 and 2008 were reviewed. National annual hospitalization and death rates for asthma were extracted. <b><i>Results:</i></b> Three hundred thousand medical records were reviewed. During the study period, lifetime asthma prevalence decreased from 9.7 to 8.1% (p = 0.002). The point prevalence of moderate-to-severe and mild persistent asthma decreased significantly from 0.88 and 3.41% to 0.36 and 2.44%, respectively, during this period. The prevalence of intermittent asthma and asthma in clinical remission for more than 3 years did not change significantly. The annual hospitalization rate for asthma decreased from 13.0 to 7.5 per 10,000 population (p &lt; 0.0001), whilst the annual death rate due to asthma decreased between 1999 and 2008 from 2.1 to 1.4 per 100,000 population (p = 0.003). <b><i>Conclusions:</i></b> The prevalence of asthma in Israeli teenage boys decreased significantly over the last decade. In addition, asthma hospitalization and asthma-related death rates in the total population also decreased.
DOI: 10.6084/m9.figshare.4570030
title: Supplementary Material for: Prevalence of Potential Retrograde Embolization Pathways in the Proximal Descending Aorta in Stroke Patients and Controls

description: <b><i>Background:</i></b> Retrograde diastolic blood flow in the proximal descending aorta (DAo) connecting complex plaques (≥4 mm thick) with brain-supplying supra-aortic arteries may constitute a source of stroke. Yet, data only from high-risk populations (cryptogenic stroke patients with aortic atheroma ≥3 mm) regarding the prevalence of this potential stroke mechanism are available. We aimed to quantify the frequency of this mechanism in unselected patients with cryptogenic stroke after routine diagnostics and controls without a history of stroke. <b><i>Methods:</i></b> 88 patients (67 stroke patients, 21 cardiac controls) were prospectively included. 3D T1-weighted bright blood MRI of the aorta was applied for the detection of complex DAo atheroma. ECG-triggered and navigator-gated 4D flow MRI allowed measuring time-resolved 3D blood flow in vivo. Potential retrograde embolization pathways were defined as the co-occurrence of complex plaques and retrograde blood flow in the DAo reaching the outlet of (a) the left subclavian artery, (b) the left common carotid artery, or/and (c) the brachiocephalic trunk. The frequency of these pathways was analyzed by importing 2D plaque images into 3D blood flow visualization software. <b><i>Results:</i></b> Complex DAo plaques were more frequent in stroke patients (44 in 31/67 patients (46.3%) vs. 5 in 4/21 controls (19.1%); p = 0.039), especially in older patients (29/46 (63.04%) patients ≥60 years of age with 41 plaques vs. 2/21 (9.14%) patients &lt;60 years of age with 3 plaques; p &lt; 0.001). Contrary to our assumption, retrograde diastolic blood flow at the DAo occurred in every patient irrespective of the existence of plaques with a similar extent in both groups (26 ± 14 vs. 32 ± 18 mm; p = 0.114). Therefore, only the higher prevalence of complex DAo plaques in stroke patients resulted in a three times higher frequency of potential retrograde embolization pathways compared to controls (22/67 (32.8%) vs. 2/21 (9.5%) controls; p = 0.048). <b><i>Conclusions:</i></b> This study revealed that retrograde flow in the descending aorta is a common phenomenon not only in stroke patients. The existence of potential retrograde embolization pathways depends mainly on the occurrence of complex plaques in the area 0 to ∼30 mm behind the outlet of the left subclavian artery, which is exposed to flow reversal. In conclusion, we have shown that the frequency of potential retrograde embolization pathways was significantly higher in stroke patients suggesting that this mechanism may play a role in retrograde brain embolism.
DOI: 10.6084/m9.figshare.4570027
title: Supplementary Material for: Association between a Genetic Variant in the hsa-miR-146a Gene and Cancer Risk: An Updated Meta-Analysis

description: <strong><em>Background and Aims:</em></strong> A large number of studies have investigated the association between the potentially functional genetic variant rs2910164 located in the <i>hsa-miR-146a</i> gene and susceptibility to various types of cancer. Nevertheless, the results obtained in these studies are contradictory. Therefore, we conducted a meta-analysis of data from eligible reports comprising a total of 28,359 cases and 41,678 controls. <b><i>Methods:</i></b> The literature included in this meta-analysis was selected from the PubMed database. Quantitative data synthesis was performed by using the OpenMeta-analyst software. <b><i>Results:</i></b> The meta-analysis yielded no evidence of an association between rs2910164 and the overall cancer risk. Conversely, the C allele of this genetic variant was found to be associated with a decreased risk of developing bladder and cervical cancer in multiple genetic models. The same direction of association was found for the C allele and liver cancer, gastric cancer and oral squamous cell carcinoma risk. In contrast to these results, the same allelic variant of rs2910164 was found to confer an increased risk of developing lung cancer. The stratified meta-analysis based on ethnicity did not show significant differences in the association between rs2910164 and cancer risk in populations with different ethnic backgrounds. <b><i>Conclusion:</i></b> We conclude that rs2910164 may represent a valuable biomarker associated with the risk of developing specific types of cancer.
DOI: 10.6084/m9.figshare.4570021
title: Supplementary Material for: Anti-PLA2R Antibodies as a Prognostic Factor in PLA2R-Related Membranous Nephropathy

description: <strong><em>Background:</em></strong> The natural course of idiopathic membranous nephropathy (MN) varies, as it is known through favorable outcomes in most patients. However, one third of patients with idiopathic MN will slowly progress to end-stage renal disease (ESRD). To prevent disease progression, patients at high risk to develop ESRD are treated with immunosuppressive agents. Therefore, a correct selection of patients who need immunosuppressive treatment is important. <b><i>Methods:</i></b> Here, we evaluated the prognostic value of anti-phospholipase A2 receptor 1 antibody (anti-PLA2R) levels regarding clinical outcome in a well-defined cohort of 73 PLA2R-related MN patients with long-term follow-up. At baseline, patients were subdivided into patients with either low or high antibody levels based on ELISA testing. <b><i>Results:</i></b> Spontaneous remission rates were highest among patients with low anti-PLA2R levels (79%; hazard ratio 2.72 (95% CI 1.22-6.08), p = 0.02) after a median follow-up of 2.9 (95% CI 0.8-5.0, p &lt; 0.001) years, whereas high anti-PLA2R levels were associated with persistent proteinuria (p = 0.04) and/or the need for immunosuppressive therapy (p &lt; 0.001). Renal survival rates were 97% at 5 years, 93% at 10 years, and 89% at 15 years; however, this was not different between the anti-PLA2R groups. ESRD occurred significantly faster in patients with severe proteinuria as compared to patients with either mild (p = 0.02) or moderate proteinuria (p = 0.05). <b><i>Conclusions:</i></b> Low anti-PLA2R levels may predict spontaneous remissions in patients with PLA2R-related MN. Therefore, we suggest that quantification of anti-PLA2R is of value to monitor these patients.
DOI: 10.6084/m9.figshare.4570024
title: Supplementary Material for: Effect of Laparoscopic Antireflux Surgery on Esophageal Motility

description: <b><i>Background/Aims:</i></b> The effect of laparoscopic antireflux surgery on esophageal motility is incompletely understood, and any indication for this procedure in patients with motility disorder is disputed in literature. We evaluated the influence of laparoscopic Nissen fundoplication on impaired esophageal motility. <b><i>Methods:</i></b> In this pathological manometric study, we divided the patients into two groups preoperatively: the hypomotility group (mean amplitude of esophageal contraction wave &lt;40 mm Hg; HYPO group, n = 11) and the normal group (mean amplitude of esophageal contraction wave &gt;40 mm Hg; NORM group, n = 43). The amplitudes of esophageal contraction waves 3 and 8 cm above the lower esophageal sphincter and the percentage of peristaltic contraction waves of the tubular esophagus were analyzed pre- and postoperatively. <b><i>Results:</i></b> In total, 54 patients with GERD underwent esophageal manometry before and 6 months after Nissen fundoplication. The length and pressure of the lower esophageal sphincter were increased in both groups postoperatively (p &lt; 0.01). Patients in the HYPO group (n = 11) showed a statistically significant increase of mean amplitude of esophageal contraction (32.8 vs. 57.3 mm Hg; p &lt; 0.01), while no change was found in the NORM group (n = 43). A total of 72% of patients with preoperative motility disorder showed normal postoperative manometry. <b><i>Conclusion:</i></b> Nissen fundoplication normalizes esophageal motility, especially in patients with preoperative hypomotility. Patients with impaired esophageal motility should not per se be excluded from antireflux surgery.
DOI: 10.6084/m9.figshare.4570027.v1
title: Supplementary Material for: Association between a Genetic Variant in the hsa-miR-146a Gene and Cancer Risk: An Updated Meta-Analysis

description: <strong><em>Background and Aims:</em></strong> A large number of studies have investigated the association between the potentially functional genetic variant rs2910164 located in the <i>hsa-miR-146a</i> gene and susceptibility to various types of cancer. Nevertheless, the results obtained in these studies are contradictory. Therefore, we conducted a meta-analysis of data from eligible reports comprising a total of 28,359 cases and 41,678 controls. <b><i>Methods:</i></b> The literature included in this meta-analysis was selected from the PubMed database. Quantitative data synthesis was performed by using the OpenMeta-analyst software. <b><i>Results:</i></b> The meta-analysis yielded no evidence of an association between rs2910164 and the overall cancer risk. Conversely, the C allele of this genetic variant was found to be associated with a decreased risk of developing bladder and cervical cancer in multiple genetic models. The same direction of association was found for the C allele and liver cancer, gastric cancer and oral squamous cell carcinoma risk. In contrast to these results, the same allelic variant of rs2910164 was found to confer an increased risk of developing lung cancer. The stratified meta-analysis based on ethnicity did not show significant differences in the association between rs2910164 and cancer risk in populations with different ethnic backgrounds. <b><i>Conclusion:</i></b> We conclude that rs2910164 may represent a valuable biomarker associated with the risk of developing specific types of cancer.
DOI: 10.6084/m9.figshare.4570030.v1
title: Supplementary Material for: Prevalence of Potential Retrograde Embolization Pathways in the Proximal Descending Aorta in Stroke Patients and Controls

description: <b><i>Background:</i></b> Retrograde diastolic blood flow in the proximal descending aorta (DAo) connecting complex plaques (≥4 mm thick) with brain-supplying supra-aortic arteries may constitute a source of stroke. Yet, data only from high-risk populations (cryptogenic stroke patients with aortic atheroma ≥3 mm) regarding the prevalence of this potential stroke mechanism are available. We aimed to quantify the frequency of this mechanism in unselected patients with cryptogenic stroke after routine diagnostics and controls without a history of stroke. <b><i>Methods:</i></b> 88 patients (67 stroke patients, 21 cardiac controls) were prospectively included. 3D T1-weighted bright blood MRI of the aorta was applied for the detection of complex DAo atheroma. ECG-triggered and navigator-gated 4D flow MRI allowed measuring time-resolved 3D blood flow in vivo. Potential retrograde embolization pathways were defined as the co-occurrence of complex plaques and retrograde blood flow in the DAo reaching the outlet of (a) the left subclavian artery, (b) the left common carotid artery, or/and (c) the brachiocephalic trunk. The frequency of these pathways was analyzed by importing 2D plaque images into 3D blood flow visualization software. <b><i>Results:</i></b> Complex DAo plaques were more frequent in stroke patients (44 in 31/67 patients (46.3%) vs. 5 in 4/21 controls (19.1%); p = 0.039), especially in older patients (29/46 (63.04%) patients ≥60 years of age with 41 plaques vs. 2/21 (9.14%) patients &lt;60 years of age with 3 plaques; p &lt; 0.001). Contrary to our assumption, retrograde diastolic blood flow at the DAo occurred in every patient irrespective of the existence of plaques with a similar extent in both groups (26 ± 14 vs. 32 ± 18 mm; p = 0.114). Therefore, only the higher prevalence of complex DAo plaques in stroke patients resulted in a three times higher frequency of potential retrograde embolization pathways compared to controls (22/67 (32.8%) vs. 2/21 (9.5%) controls; p = 0.048). <b><i>Conclusions:</i></b> This study revealed that retrograde flow in the descending aorta is a common phenomenon not only in stroke patients. The existence of potential retrograde embolization pathways depends mainly on the occurrence of complex plaques in the area 0 to ∼30 mm behind the outlet of the left subclavian artery, which is exposed to flow reversal. In conclusion, we have shown that the frequency of potential retrograde embolization pathways was significantly higher in stroke patients suggesting that this mechanism may play a role in retrograde brain embolism.
DOI: 10.6084/m9.figshare.4570015
title: Supplementary Material for: Changes in Gene Expression in PBMCs Profiles of PPARα Target Genes in Obese and Non-Obese Individuals During Fasting

description: <b><i>Background:</i></b> The prevalence of obesity has risen dramatically and the World Health Organization estimates that 700 million people will be obese worldwide by 2015. Approximately, 50% of the Brazilian population above 20 years of age is overweight, and 16% is obese. <b><i>Aim:</i></b> This study aimed to evaluate the differences in the expression of PPARα target genes in human peripheral blood mononuclear cells (PBMCs) and free fatty acids (FFA) in obese and non-obese individuals after 24 h of fasting. We first presented evidence that Brazilian people exhibit expression changes in PPARα target genes in PBMCs under fasting conditions. <b><i>Methods:</i></b> Q-PCR was utilized to assess the mRNA expression levels of target genes. <b><i>Results:</i></b> In both groups, the FFA concentrations increased significantly after 24 h of fasting. The basal FFA mean concentration was two-fold higher in the obese group compared with the non-obese group. After fasting, all genes evaluated in this study showed increased expression levels compared with basal expression in both groups. <b><i>Conclusion:</i></b> However, our results reveal no differences in gene expression between the obese and non-obese, more studies are necessary to precisely delineate the associated mechanisms, particularly those that include groups with different degrees of obesity and patients with diabetes mellitus type 2 because the expression of the main genes that are involved in β-oxidation and glucose level maintenance are affected by these factors.
DOI: 10.6084/m9.figshare.4570006
title: Supplementary Material for: Osteogenic Differentiation of Late-Outgrowth CD45-Negative Endothelial Progenitor Cells

description: <b><i>Background/Aims:</i></b> Late-outgrowth CD45-negative endothelial colony-forming cells are implicated to be circulating endothelial progenitor cells (EPCs), as they express endothelial cell markers and can directly form blood vessels. As these cells share characteristics of other progenitor cell phenotypes, late-outgrowth EPCs were assayed for both multilineage differentiation capability and for markers of pluripotency. <b><i>Methods:</i></b> Clonal single-colony late-outgrowth EPCs were derived from human cord blood and assayed both for multilineage differentiation capability in vitro and for markers of pluripotency by qPCR. <b><i>Results:</i></b> Under osteogenic growth conditions, these EPCs expressed the osteogenic markers RUNX2, COL1A1, ALPL, and osteocalcin and demonstrated calcium deposition and bone mineralization. Endothelial colony-forming cells expressed markers associated with induced pluripotent stem cells, including SOX2, POU5F1, c-MYC, and KLF4. <b><i>Conclusions:</i></b> Late-outgrowth EPCs express markers associated with pluripotency and can directly express an osteogenic phenotype under bone differentiation conditions in vitro.
DOI: 10.6084/m9.figshare.4569997
title: Supplementary Material for: In vitro Antimicrobial Activities of 1-Methoxyficifolinol, Licorisoflavan A, and 6,8-Diprenylgenistein against Streptococcus mutans

description: The objective of the study was to investigate the antimicrobial effects of purified single compounds from ethanol-extracted licorice root on <i>Streptococcus mutans</i>. The crude licorice root extract (CLE) was obtained from <i>Glycyrrhiza uralensis</i>, which was subjected to column chromatography to separate compounds. Purified compounds were identified by mass spectrometry and nuclear magnetic resonance. Antimicrobial activities of purified compounds from CLE were evaluated by determining the minimum inhibitory concentration and by performing time-kill kinetics. The inhibitory effects of the compounds on biofilm development were evaluated using crystal violet assay and confocal microscopy. Cell toxicity of substances to normal human gingival fibroblast (NHGF) cells was tested using a methyl thiazolyl tetrazolium assay. Chlorhexidine digluconate (CHX) was used in the control group. Three antimicrobial flavonoids, 1-methoxyficifolinol, licorisoflavan A, and 6,8-diprenylgenistein, were isolated from the CLE. We found that the three flavonoids and CHX had bactericidal effects on <i>S. mutans</i> UA159 at the concentration of ≥4 and ≥1 µg/ml, respectively. The purified compounds completely inhibited biofilm development of<i> S. mutans</i> UA159 at concentrations over 4 μg/ml, which was equivalent to 2 μg/ml of CHX. Confocal analysis showed that biofilms were sparsely scattered in the presence of over 4 μg/ml of the purified compounds. However, the three compounds purified from CLE showed less cytotoxic effects on NHGF cells than CHX at these biofilm-inhibitory concentrations. Our results suggest that purified flavonoids from CLE can be useful in developing oral hygiene products, such as gargling solutions and dentifrices for preventing dental caries.