Miracle-dz/UniFAR-FTUs huggingface dataset:
MALAT1/miR-15b-5p/MAPK1 mediates endothelial progenitor cells autophagy and affects coronary atherosclerotic heart disease via mTOR signaling pathway

Objective: Present study focused on the influence of lncRNA MALAT1 on coronary atherosclerotic heart disease (CAD) by regulating miR-15b-5p/MAPK1 and mTOR signaling pathway. Method: Differentially expressed genes and activated pathway were investigated through bioinformatics analysis. QRT-PCR was conducted to verify expression of MALAT1, miR-15b-5p and MAPK1 in CAD blood samples and endothelial progenitor cells (EPCs). In addition, the interactions among MALAT1, miR-15b-5p and MAPK1 were revealed by Luciferase reporter assay. Cell autophagy of EPCs was examined by Cyto-ID Autophagy Detection Kit and transmission electron microscope. MTT assay and flow cytometry were carried out to assess cell viability and apoptosis in different interference conditions. Western blot was performed to testify the expression of pERK1/2 (MAPK1), phosphorylated mTOR, ATG1 and LC3-II. Vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were detected by qRT-PCR. Finally, the effect of lncRNA MALAT1 on cell autophagy and atherogenesis was tested in vivo. Results: MALAT1 was overexpressed in CAD blood samples and EPCs. Knockdown of MALAT1 and MAPK1 promoted cell viability, autophagy and further suppressed the development of CAD. AntagoMALAT1 protects mice against atherosclerosis. Conclusion: LncRNA MALAT1 inhibited EPCs autophagy and increased cell viability while repressed apoptosis of CAD via activating mTOR signaling pathway.
Preventive effects of pneumococcal and influenza vaccines on community-acquired pneumonia in older individuals in Japan: a case-control study

ABSTRACT At present, there are few reports that have clarified the effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPSV23) against all-cause pneumonia or pneumococcal pneumonia in community-acquired pneumonia (CAP) in older individuals in Japan. We conducted a hospital-based matched case-control study to investigate separately the preventive effects of PPSV23 and trivalent influenza vaccine (TIV) on all-cause CAP and pneumococcal CAP in older individuals in Japan. Cases were individuals aged 65 years or older who were newly diagnosed with CAP from October 2010 to September 2014. Two control patients with a different disease (one respiratory medicine and one non-respiratory medicine) matched for sex, age, date of outpatient visit, and medical institution were selected for each case. Odds ratios (ORs) and 95% confidence intervals (CIs) of PPSV23 and TIV for the occurrence of all-cause CAP and pneumococcal CAP were calculated using conditional and unconditional logistic regression models. The analysis included 161 cases and 308 controls from the 4-year period. The adjusted OR for the occurrence of all-cause CAP was 0.76 (95%CI = 0.44–1.32) with PPSV23 vaccination and 0.79 (95%CI = 0.50–1.25) with TIV vaccination compared with unvaccinated individuals. When the outcome index was restricted to pneumococcal CAP, the adjusted OR significantly decreased to 0.23 (95%CI = 0.08–0.66) with PPSV23 vaccination, but not with TIV vaccination (adjusted OR = 0.65, 95%CI = 0.31–1.36). PPSV23 vaccination is likely effective in reducing incidence of pneumococcal CAP in older individuals, although its preventive effect for all-cause CAP has not been achieved.
The impact of new guidelines on the prevalence of hypertension in children: A cross‐sectional evaluation

Updated clinical practice guidelines for screening blood pressures in pediatric patients were published in 2017. They differ from the previous guideline, known as the Fourth Report, providing updated population normal values and blood pressure categorization. We hypothesized that the prevalence of abnormal blood pressure in children and adolescents would be higher using the new clinical practice guidelines. We present a cross‐sectional study of screening blood pressure values for children 3 to 18 years of age obtained during well‐child visits at a primary care clinic. All blood pressure values were categorized using both the Fourth Report and the Clinical Practice Guideline. A total of 2635 blood pressure measurements were extracted, and 2600 were eligible for analysis. Using the clinical practice guideline, the prevalence of hypertension increased to 17.85% compared to 9.5% per the Fourth Report (P < 0.0001). Of those patients classified as having a normal blood pressure by the Fourth Report, 12% changed to abnormal when applying the Clinical Practice Guideline. All subgroups had a significant increase in the prevalence of abnormal blood pressure. The most dramatic increase in the prevalence of stage 1 and stage 2 hypertension was seen in six patient subgroups: males, 3‐12 years of age, Hispanic ethnicity, race designated as other, normal weight, and overweight. Applying the new Clinical Practice Guideline increased the prevalence of elevated blood pressure and stage 1 and stage 2 hypertension in children and adolescents, requiring more follow‐up and intervention than previously expected for this patient population.
Extracellular Lumican Inhibits Pancreatic Cancer Cell Growth and Is Associated with Prolonged Survival after Surgery

Purpose: To evaluate the relevance between lumican expression patterns and the clinical course of patients with pancreatic ductal adenocarcinoma (PDAC), and to investigate the role of lumican in PDAC progression. Experimental Design: One hundred thirty-one patient tumors were chosen for tissue microarray staining, and Cox regression analysis was used to test the associations between lumican expression and clinical, pathologic, and oncologic outcomes in all patients. Primary PDAC cells and recombinant human lumican protein were used to establish a working model to mimic the in vivo interactions between stromal lumican and PDAC cells. Using this model, we tested the effects of lumican on EGFR signaling via Akt and hypoxia-inducible factor-1α (HIF1α) and its subsequent influence on glucose consumption, lactate production, intracellular ATP, and apoptotic cell death. Results: Lumican was present in the stroma surrounding PDAC cells in roughly one-half of primary tumors and the direct xenografts. Patients with stromal lumican were associated with a profound reduction in metastatic recurrence after surgery and 3-fold longer survival than patients without stromal lumican. In PDAC cells, extracellular lumican reduced EGFR expression and phosphorylation through enhanced dimerization and internalization of EGFR and the resultant inhibition of Akt kinase activity. Lumican also reduced HIF1α expression and activity via Akt. PDAC cells with enhanced HIF1α activity were resistant to lumican-induced inhibition of glucose consumption, lactate production, intracellular ATP, and apoptosis. Conclusions: There is a positive association between stromal lumican in primary PDAC tumors and prolonged survival after tumor resection. Lumican plays a restrictive role in EGFR-expressing pancreatic cancer progression. Clin Cancer Res; 20(24); 6529–40. ©2014 AACR.
Role of vagal activation in postprandial glucose metabolism after gastric bypass in individuals with and without hypoglycaemia

Patients who have undergone gastric bypass surgery (GB) have enhanced postprandial hyperinsulinaemia and a greater incretin effect is apparent. In the present study, we sought to determine the effect of vagal activation, a neural component of the enteroinsular axis, on postprandial glucose metabolism in patients with and without hypoglycaemia after GB. Seven patients with documented post‐GB hypoglycaemia, seven asymptomatic patients without hypoglycaemia post‐GB, and 10 weight‐matched non‐surgical controls with normal glucose tolerance were recruited. Blood glucose, and islet hormone and incretin secretion were compared during mixed meal tolerance tests (MMTs) with and without prior sham‐feeding on two separate days. Sham feeding preceding the MMT caused a more rapid increase in prandial blood glucose levels but lowered overall glycaemia in all three groups (P < 0.05). Sham feeding had a similar effect to increase early (P < 0.05), but not overall, meal‐induced insulin secretion in the three groups. Prandial glucagon concentrations were significantly greater in the GB groups, and sham feeding accentuated this response (P < 0.05). The effect of vagal activation on prandial glucose and islet‐cell function is preserved in patients who have undergone GB, in those both with and without hypoglycaemia.
Quantitative in Situ Analysis of FoxP3+ T Regulatory Cells on Transplant Tissue Using Laser Scanning Cytometry

There is abundant evidence that immune cells infiltrating into a transplanted organ play a critical role for destructive inflammatory or regulatory immune reactions. Quantitative in situ analysis (i.e., in tissue sections) of immune cells remains challenging due to a lack of objective methodology. Laser scanning cytometry (LSC) is an imaging-based methodology that performs quantitative measurements on fluorescently and/or chromatically stained tissue or cellular specimens at a single-cell level. In this study, we have developed a novel objective method for analysis of immune cells, including Foxp3+ T regulatory cells (Tregs), on formalin-fixed/paraffin-embedded (FFPE) transplant biopsy sections using iCys® Research Imaging Cytometer. The development of multiple immunofluorescent staining was established using FFPE human tonsil sample. The CD4/CD8 ratio and the population of Tregs among CD4+ cells were analyzed using iCys and compared with the results from conventional flow cytometry analysis (FCM). Our multiple immunofluorescent staining techniques allow obtaining clear staining on FFPE sections. The CD4/CD8 ratio analyzed by iCys was concordant with those obtained by FCM. This method was also applicable for liver, small intestine, kidney, pancreas, and heart transplant biopsy sections and provide an objective quantification of Tregs within the grafts.
Quantitative proteomic analysis of A549 cells infected with human adenovirus type 2

Human adenovirus (HAdV‐2) is considered a common agent of respiratory tract infection in the human, especially in children. Virus infection is believed to modify host cell expression necessary for its replication and therefore cell proteome can reflect the changes of specific cellular pathways during infection. This study aims to identify differentially expressed proteins of A549 cells in response to HAdV‐2 infection using a label‐free liquid chromatography‐high‐resolution tandem mass spectrometry strategy (LC‐MS/MS) at 24 and 48 hpi. A total of 248 and 216 proteins were deregulated by 1.35‐fold at 24 and 48 hpi, respectively. Among them, 155 were upregulated at 24 hpi and 86 at 48 hpi, whereas 93 and 130 were downregulated at 24 and 48 hpi, respectively. The identified proteins were involved in different pathways as energy, transcription, protein synthesis, cytoskeleton, rescue and defense, cell cycle, DNA processing, transportation, and metabolism. Glycolytic pathway and histone deregulated proteins were further confirmed by chemical testing and immunofluorescence, respectively. The results suggest that the identified proteins influenced HAdV‐2 infection in the context of viral replication and propagation. This study complement proteomic data obtained from previous studies and reinforce the understanding of the relationship between HAdV and host cell.
A comparative analysis of various surgical approaches of nephron-sparing surgery and correlation of histopathological grade with RENAL nephrometry score in renal cell carcinoma

Background: Nephron-sparing surgery (NSS) is the standard of care for small renal masses whenever feasible. This study aims to evaluate the perioperative outcomes of NSS performed by open (open partial nephrectomy [OPN]) or laparoscopic (laparoscopic PN [LPN]) or robotic (robotic PN [RPN]) approach over the past 6 years and to study the correlation of histopathological grade of renal cell carcinoma with the RENAL score. Materials and Methods: A retrospective analysis of prospectively collected data of all patients who underwent NSS was done. Results: A total of 135 patients underwent NSS. The mean tumour size was 4.4 cm. About 61 patients underwent OPN, 24 had LPN and 50 had RPN. Although tumour size was larger in OPN group (P = 0.01), tumour complexity based on the RENAL score was similar in OPN and RPN groups (P = 0.15). The OPN group had shorter operative time (P = 0.008) but more blood loss (P = 0.001) and length of hospital stay (P = 0.049) as compared to LPN or RPN group. Maximum radiological diameter of tumour (P = 0.017) appeared to be a significant predictor of operative time, while the open surgical approach (P = 0.003) and tumour stage (P = 0.044) were found to be significant predictors of blood loss. Hilar clamping time was similar in OPN and RPN groups (P = 0.054) but higher in LPN group (P = 0.01). However, post-operative decline in renal function (estimated glomerular filtration rate) (P = 0.08) and margin status were comparable among the three groups. The most common histopathology was clear cell carcinoma (70%), and RENAL score was identified as a significant predictor of histopathological grade of tumour (P = 0.008). Conclusion: Open, laparoscopic and robotic approaches to PN provide similar patient outcomes. OPN was usually preferred for larger tumours. The post-operative decline in renal functions and complications were comparable among the three approaches. RENAL score correlated significantly with histopathological grade and hence could help in predicting tumour behaviour pre-operatively.
Tricuspid regurgitant jet velocity and hospitalization in Tanzanian children with sickle cell anemia

Elevated tricuspid regurgitant velocity (TRV) measured by echocardiogram predicts death in adult sickle cell anemia (SCA)[1][1]–[4][2] and occurs in children,[5][3]–[9][4] although etiology and association with survival and complications requiring hospitalization are unknown. In children,
Effectiveness of lumbar epidural injection in patients with chronic spinal stenosis accompanying redundant nerve roots

Abstract Redundant nerve root syndrome (RNRS) is a phenomenon characterized by the presence of elongated, enlarged, tortuous nerve roots in the lumbar subarachnoid space. It is unclear whether RNRS is caused by spinal stenosis or causes these symptoms. This study evaluated the effects of lumbar epidural steroid injection (LESI) on patients with RNRS and assessed factors associated with RNRS. This retrospective observational cohort study was conducted at a single pain clinic of a university hospital. The medical records of 172 outpatients presenting with low back and/or leg pain from July to December 2014 were analyzed. Pain intensity (numeric rating scale [NRS]) and functional status were assessed at baseline and 2, 4, and 12 weeks after the LESI. Patients were considered moderate responders if they showed a 3-point or >30% reduction in baseline NRS, or said “better than 30%,” “a little better,” or “I feel an effect. ” Patients were considered substantial responders if they showed a 5-point or >50% reduction in baseline NRS, or said “better than 50%,” “very good,” or “much better. ” Generalized estimating equation (GEE) analysis was performed to identify the factors associated with moderate response to LESI. Factors associated with RNRS were also determined by logistic regression analysis. The proportions of both moderate and substantial responders at 2, 4, and 12 weeks were significantly lower in patients with than without RNRS. GEE analysis showed that RNRS were the only factor significantly associated with moderate response to LESI (OR = 0.400; 95% CI, 0.253–0.632; P < .001). The distance from the conus medullaris to the closest level of stenosis was shorter in patients with than without RNRS (P < .001) and was the only independent factor associated with RNRS on multivariate logistic regression analysis (OR = 0.972; P < .001). LESI was less effective in patients with than without RNRS. The only independent factor significantly associated with RNRS was the distance from the conus medullaris to the nearest moderate stenosis.
Pioglitazone increases VEGFR3 expression and promotes activation of M2 macrophages via the peroxisome proliferator-activated receptor γ

The peroxisome proliferator-activated receptor γ (PPARγ) agonist pioglitazone has been widely used in previous studies to ameliorate diabetes mellitus and regulate inflammation. However, the present study aimed to investigate the effect of pioglitazone on macrophages and determine its impact on renal fibrosis in vivo. Firstly, bone marrow-derived macrophages (BMDM) were used to detect the effects of pioglitazone on macrophages in vitro. It was demonstrated that pioglitazone promoted M2 macrophage activation and induced vascular endothelial growth factor receptor 3 (VEGFR3) upregulation in a PPARγ-dependent manner. Furthermore, pioglitazone increased macrophage proliferation and macrophage VEGFR3 expression in a murine unilateral ureteral obstruction (UUO) model; however, it had no therapeutic effect on renal fibrosis in vivo. Therefore, the results in the present study implied that presence of M2 macrophages may inhibit pioglitazone's ability to attenuate UUO-induced renal fibrosis. In addition, the results demonstrated that macrophage-associated VEGFR3 could be induced by pioglitazone, although it is still unclear what role VEGFR3+ M2 macrophages have in renal fibrosis.
Temporal Trends in Ischemic Heart Disease Mortality in 21 World Regions, 1980 to 2010: The Global Burden of Disease 2010 Study

Background— Ischemic heart disease (IHD) is the leading cause of death worldwide. The Global Burden of Diseases, Risk Factors and Injuries 2010 Study estimated global and regional IHD mortality from 1980 to 2010. Methods and Results— Sources for IHD mortality estimates were country-level surveillance, verbal autopsy, and vital registration data. Regional income, metabolic and nutritional risk factors, and other covariates were estimated from surveys and a systematic review. An estimation and validation process led to an ensemble model of IHD mortality for 21 world regions. Globally, age-standardized IHD mortality has declined since the 1980s, and high-income regions (especially Australasia, Western Europe, and North America) experienced the most remarkable declines. Age-standardized IHD mortality increased in former Soviet Union countries and South Asia in the 1990s and attenuated after 2000. In 2010, Eastern Europe and Central Asia had the highest age-standardized IHD mortality rates. More IHD deaths occurred in South Asia in 2010 than in any other region. On average, IHD deaths in South Asia, North Africa and the Middle East, and sub-Saharan Africa occurred at younger ages in comparison with most other regions. Conclusions— In most world regions, particularly in high-income regions, age-standardized IHD mortality rates have declined significantly since 1980. High age-standardized IHD mortality in Eastern Europe, Central Asia, and South Asia point to the need to prevent and control established risk factors in those regions and to research the unique behavioral and environmental determinants of higher IHD mortality.
Comparison of the effects of modified and full-coverage thermoplastic retainers on occlusal contacts.

AIM The purpose of this prospective study was to determine the number of contacts in centric occlusion during retention with modified and full-coverage thermoplastic Essix retainers. METHODS This research was based on 36 patients who were randomly assigned to wear either modified (18 patients) or full-coverage (18 patients) Essix retainers. Silicone-based bite registrations were used to record occlusal contacts at the beginning (T1), end of full-time (6 months; T2), and end of night-time (3 months; T3) wear of retainers. The occlusal contacts determined in treated patients were compared with the values of 18 untreated "normal" Class I subjects. Bonferroni-adjusted Wilcoxon and Kruskal-Wallis tests were used to evaluate intra- and intergroup differences. RESULTS Total posterior contacts increased significantly at T3 compared to T1 and T2 only in the modified Essix group. Non-ideal and total contacts on premolars, non- ideal and actual contacts on first molars, and actual contacts on second molars increased significantly at T3 in the modified Essix group. No significant increase was determined in the final total posterior contacts in the full-coverage Essix group. Actual contacts on premolars and first molars and total posterior actual contacts were significantly greater at T3 in the modified Essix group compared to the full-coverage Essix Group. Also the number of final posterior ideal contacts in the modified Essix group was greater than in the normal sample. Total anterior contacts decreased significantly in the modified Essix group, whereas they increased significantly in the full-coverage Essix group. CONCLUSIONS Increase in posterior contacts was achieved only during night-time wear of modified Essix retainers.
In vivo reflectance confocal microscopy of oral lichen planus

In vivo reflectance confocal microscopy (RCM) is an imaging technique that can virtually biopsy vital tissues, noninvasively and in real time. It results in horizontal virtual slices at a microscopic resolution that correlates well with conventional histopathology. Despite the widespread use of RCM in dermatology, it is still rarely applied to the study of oral pathologies. The aim of the present work is to describe RCM cellular and architectural findings in oral mucosae affected by oral lichen planus (OLP).
Structure, dynamics and roX2-lncRNA binding of tandem double-stranded RNA binding domains dsRBD1,2 of Drosophila helicase Maleless

Maleless (MLE) is an evolutionary conserved member of the DExH family of helicases in Drosophila. Besides its function in RNA editing and presumably siRNA processing, MLE is best known for its role in remodelling non-coding roX RNA in the context of X chromosome dosage compensation in male flies. MLE and its human orthologue, DHX9 contain two tandem double-stranded RNA binding domains (dsRBDs) located at the N-terminal region. The two dsRBDs are essential for localization of MLE at the X-territory and it is presumed that this involves binding roX secondary structures. However, for dsRBD1 roX RNA binding has so far not been described. Here, we determined the solution NMR structure of dsRBD1 and dsRBD2 of MLE in tandem and investigated its role in double-stranded RNA (dsRNA) binding. Our NMR data show that both dsRBDs act as independent structural modules in solution and are canonical, non-sequence-specific dsRBDs featuring non-canonical KKxAK RNA binding motifs. NMR titrations combined with filter binding experiments document the contribution of dsRBD1 to dsRNA binding in vitro. Curiously, dsRBD1 mutants in which dsRNA binding in vitro is strongly compromised do not affect roX2 RNA binding and MLE localization in cells. These data suggest alternative functions for dsRBD1 in vivo.