Miracle-dz/UniFAR-FTUs huggingface dataset:
Biogenesis and cytotoxicity of APOL1 renal risk variant proteins in hepatocytes and hepatoma cells

Two APOL1 gene variants, which likely evolved to protect individuals from African sleeping sickness, are strongly associated with nondiabetic kidney disease in individuals with recent African ancestry. Consistent with its role in trypanosome killing, the pro-death APOL1 protein is toxic to most cells, but its mechanism of cell death is poorly understood and little is known regarding its intracellular trafficking and secretion. Because the liver appears to be the main source of circulating APOL1, we examined its secretory behavior and mechanism of toxicity in hepatoma cells and primary human hepatocytes. APOL1 is poorly secreted in vitro, even in the presence of chemical chaperones; however, it is efficiently secreted in wild-type transgenic mice, suggesting that APOL1 secretion has specialized requirements that cultured cells fail to support. In hepatoma cells, inducible expression of APOL1 and its risk variants promoted cell death, with the G1 variant displaying the highest degree of toxicity. To explore the basis for APOL1-mediated cell toxicity, endoplasmic reticulum stress, pyroptosis, autophagy, and apoptosis were examined. Our results suggest that autophagy represents the predominant mechanism of APOL1-mediated cell death. Overall, these results increase our understanding of the basic biology and trafficking behavior of circulating APOL1 from the liver.
University of Dundee Targeted knock-down of miR 21 primary transcripts using snoMEN vectors induces apoptosis in human cancer cell lines

We have previously reported an antisense technology, ‘snoMEN vectors’, for targeted knock-down of protein coding mRNAs using human snoRNAs manipulated to contain short regions of sequence complementarity with the mRNA target. Here we characterise the use of snoMEN vectors to target the knock-down of micro RNA primary transcripts. We document the specific knock-down of miR21 in HeLa cells using plasmid vectors expressing miR21-targeted snoMEN RNAs and show this induces apoptosis. Knock-down is dependent on the presence of complementary sequences in the snoMEN vector and the induction of apoptosis can be suppressed by over-expression of miR21. Furthermore, we have also developed lentiviral vectors for delivery of snoMEN RNAs and show this increases the efficiency of vector transduction in many human cell lines that are difficult to transfect with plasmid vectors. Transduction of lentiviral vectors expressing snoMEN targeted to pri-miR21 induces apoptosis in human lung adenocarcinoma cells, which express high levels of miR21, but not in human primary cells. We show that snoMEN-mediated suppression of miRNA expression is prevented by siRNA knock-down of Ago2, but not by knock-down of Ago1 or Upf1. snoMEN RNAs colocalise with Ago2 in cell nuclei and nucleoli and can be co-immunoprecipitated from nuclear extracts by antibodies specific for Ago2.
Clinical outcomes in 1731 patients undergoing mitral valve surgery for rheumatic valve disease

Objective Unlike degenerative mitral valve (MV) disease, the advantages of valve repair procedure over replacement have been debated in rheumatic MV disease. This study aims to evaluate the impact of procedural types on long-term outcomes through analyses on a large data set from an endemic area of rheumatic disease. Methods We evaluated 1731 consecutive patients (52.3±12.5 years; 1190 women) undergoing MV surgery for rheumatic MV disease between 1997 and 2015. Long-term survival and valve-related outcomes were compared between repair and replacement procedures. To adjust for selection bias, propensity score analyses were performed. Results Patients undergoing repair were younger and had more predominant mitral regurgitation than mechanical and bioprosthetic replacement groups (61.6% vs 15.6% vs 24.4%; P<0.001). During follow-up (130.9±27.7 months), 283 patients (16.3%) died and 256 patients (14.8%) experienced valve-related complications. Propensity score matching yielded 188 pairs of repair and replacement patients that were well balanced for baseline covariates. In the matched cohort, there was no significant difference in the mortality risk between the repair and replacement groups (HR, 1.24; 95% CI 0.62 to 2.48). The risk of composite valve-related complications, however, was significantly lower in repair group (HR, 0.57; 95% CI 0.33 to 0.99) principally derived by a lower risk of haemorrhagic events (HR, 0.23; 95% CI 0.07 to 0.70). The incidence of reoperation was not significantly different between groups in the matched cohort (HR, 1.62; 95% CI 0.49 to 5.28). Conclusion Valve repair in well-selected patients with severe rheumatic MV disease led to comparable survival, but superior valve-related outcomes compared with valve replacement surgery.
NG2 proteoglycan‐expressing cells of the adult rat brain: Possible involvement in the formation of glial scar astrocytes following stab wound

Stab wound lesion to the adult central nervous system induces strong proliferative response that is followed by the formation of a dense astroglial scar. In order to determine the origin of those astrocytes composing the glial scar, the cell proliferation marker bromodeoxyuridine (BrdU) was administered to lesioned rats that were fixed 3 h or 6 days later. At 3 h after the BrdU administration, labeled nuclei were frequently associated with either NG2+ cells or microglia/macrophages, but rarely with astrocytes expressing glial fibrillary acidic protein (GFAP). Six days later, by contrast, numerous BrdU‐labeled nuclei were associated with astrocytes located along the lesion borders. After the injection of a viral vector of the green fluorescent protein (GFP) into the lesional cavity, GFP was preferentially detected within NG2‐ or GFAP‐labeled cells when lesioned animals were fixed 1 or 6 days after the injections, respectively. The combined detection of glial markers within cells present in the lesioned area indicated that, although they rarely express GFAP, the marker of mature astrocytes, NG2+ cells located along the lesion borders frequently express nestin and vimentin, i.e., two markers of immature astrocytes. Lastly, chronic treatment of lesioned rats with dexamethasone was found to inhibit the proliferation of NG2+ cells present within the lesioned area and to subsequently alter the formation of a dense astroglial scar. Taken together, these data strongly suggest that following a surgical lesion, at least a portion of the astrocytes that constitute the glial scar are issued from resident NG2+ cells. © 2004 Wiley‐Liss, Inc.
Comparison of reflux esophagitis and its complications between African Americans and non-Hispanic whites.

AIM To determine the effect of ethnicity on the severity of reflux esophagitis (RE) and its complications. METHODS A retrospective search of the endoscopy database at the University of Florida Health Science Center/Jacksonville for all cases of reflux esophagitis and its complications from January 1 to March 31, 2001 was performed. Inclusion criteria were endoscopic evidence of esophagitis using the LA classification, reflux related complications and self-reported ethnicity. The data obtained included esophagitis grade, presence of a hiatal hernia, esophageal ulcer, stricture and Barrett's esophagus, and endoscopy indication. RESULTS The search identified 259 patients with RE or its complications, of which 171 were non-Hispanic whites and 88 were African Americans. The mean ages and male/female ratios were similar in the two groups. RE grade, esophageal ulcer, stricture and hiatal hernia frequency were likewise similar in the groups. Barrett's esophagus was present more often in non-Hispanic whites than in African Americans (15.8% vs 4.5%; P < 0.01). Heartburn was a more frequent indication for endoscopy in non-Hispanic whites with erosive esophagitis than in African Americans (28.1% vs 7.9%; P < 0.001). CONCLUSION Distribution of RE grade and frequency of reflux-related esophageal ulcer, stricture and hiatal hernia are similar in non-Hispanic whites and African Americans. Heartburn was more frequently and nausea/vomiting less frequently reported as the primary endoscopic indication in non-Hispanic whites compared with African Americans with erosive esophagitis or its complications. African Americans have a decreased prevalence of Barrett's esophagus compared with non-Hispanic whites.
Human cleft lip and palate fibroblasts and normal nicotine‐treated fibroblasts show altered in vitro expressions of genes related to molecular signaling pathways and extracellular matrix metabolism

Nonsyndromic cleft lip with or without cleft palate (CLP) is a frequent craniofacial malformation caused by both genetic and environmental factors. Maternal smoking during pregnancy is a known risk factor, due to the teratogenic role of nicotine. To assess and compare the impact of CLP and nicotine, we studied the quantitative expression of genes involved in signaling pathways and extracellular matrix (ECM) metabolism in human normal nicotine‐treated (NicN) and CLP fibroblasts compared to normal control (CTRL) cells. Palatal fibroblast cultures from seven CLP children and seven age‐matched CTRL subjects were established and subconfluent cells incubated for 24 h without (CTRL and CLP fibroblasts) or with (NicN fibroblasts) 0.6 mM nicotine. Gene expressions were analyzed by real‐time quantitative PCR. For the first time, a regulated cholinergic signaling in our human fibroblasts in vitro was demonstrated. Members of TGF‐beta, retinoic acid (RA), and GABA‐ergic signaling systems were also differently regulated. Among the ECM genes, fibronectin, syndecan, integrin α2, and MMP13 genes were concordantly modulated, while integrin β5, and decorin genes were discordantly modulated. Interestingly, nicotine treatment regulated gene expressions of CD44 and CLPTM1, two candidate genes for CLP. Our findings show a positive association between nicotine treatment and CLP phenotype. Results suggest that nicotine deranges normal palate development, which might contribute to the development of a CLP malformative phenotype, through the impairment of some important signaling systems and ECM composition. J. Cell. Physiol. 222: 748–756, 2010. © 2009 Wiley‐Liss, Inc.
Health literacy is associated with health behaviour and self-reported health: A large population-based study in individuals with cardiovascular disease

Background Health literacy may constitute a modifiable determinant of health behaviour and affect cardiovascular disease prevention. This study investigates the associations between health literacy and health behaviour as well as health status. Design A cross-sectional study on a population-based sample of people with acute myocardial infarction, angina pectoris or stroke (N = 3116). Methods Health literacy was assessed using two dimensions from the Health Literacy Questionnaire: ‘understanding health information’ and ‘engaging with healthcare providers’. Health behaviour included physical activity, dietary habits, smoking, alcohol consumption and body mass index. Health status was examined using Short Form Health Survey 12 version 2 (four-week recall) (physical and mental components). We used regression analyses to examine the associations. Results ‘Understanding health information’ was inversely associated with physical inactivity (odds ratio (OR) 0.48 (0.39;0.59), unhealthy diet (OR 0.64 (0.47;0.88)), underweight (OR 0.43 (0.21;0.89)) and obesity (OR 0.79 (0.63;0.99)). ‘Engaging with healthcare providers’ was inversely associated with physical inactivity (OR 0.64 (0.53;0.77)), less than healthy diet (OR 0.79 (0.64;0.96)) and daily smoking (OR 0.81 (0.66;1.0)). An increase in ‘understanding health information’ as well as ‘engaging with healthcare providers’ was associated with an increase in both physical and mental health status. Conclusions The findings suggest that aspects of health literacy are associated with health status and health behaviour in cardiovascular patients and should be considered in interventions regarding cardiovascular disease prevention.
Experimental and mathematical study of the influence of growth factors on the growth kinetics of adult human articular chondrocytes

This study aimed at determining how kinetic parameters of adult human articular chondrocytes (AHAC) growth are modulated by the growth factor combination TGFβ1, FGF‐2, and PDGF BB (TFP), recently shown to stimulate AHAC proliferation. AHAC, isolated from cartilage biopsies of three individuals, were cultured in medium without (CTR) or with TFP. For growth curves, AHAC were seeded at 1,000 cells/cm2 and cultured for 12 days, with cell numbers measured fluorimetrically in the same wells every 12 h. For microcolony tests, AHAC were seeded at 2.5 cells/cm2 and cultured for 6 days, with cell numbers determined for each microcolony by phase contrast microscopy every 8 h. A mathematical model combining delay and logistic equations was developed to capture the growth kinetic parameters and to enable the description of the complete growth process of the cell culture. As compared to CTR medium, the presence of TFP increased the number of cells/well starting from the fifth day of culture, and a four‐fold larger cell number was reached at confluency. For single microcolonies, TFP reduced the time for the first cell division by 26.6%, the time for subsequent cell divisions (generation time) by 16.8%, and the percentage of quiescent cells (Qc) by 42.5%. The mathematical model fitted well the experimental data of the growth kinetic. Finally, using both microcolony tests and the mathematical model, we determined that prolonged cell expansion induces an enrichment of AHAC with shorter first division time, but not of those with shorter generation time. © 2005 Wiley‐Liss, Inc.
Involvement of Reactive Oxygen Species in the Action of Ciprofloxacin against Escherichia coli

ABSTRACT Ciprofloxacin is an important and commonly used member of the fluoroquinolone group of antibiotics. Ciprofloxacin inhibits DNA topoisomerase II and DNA topoisomerase IV activities, eventually leading to bacterial cell death. In addition, an increase of reactive oxygen species in the bacterial cells in response to ciprofloxacin has been shown. We investigated the role of reactive oxygen species in the antibacterial action of ciprofloxacin by studying the effects of different antioxidant compounds on ciprofloxacin susceptibility of Escherichia coli. Among the antioxidants checked, glutathione and ascorbic acid provided substantial protection against ciprofloxacin. The involvement of superoxide anion (O2−) and hydrogen peroxide (H2O2) in the antibacterial action of ciprofloxacin was analyzed using superoxide dismutase, catalase, and alkyl hydroperoxide reductase knockout strains of E. coli. The effects of multicopy sod genes on ciprofloxacin susceptibility of E. coli were also analyzed. On the basis of our results, we conclude that O2− and H2O2 may be involved in antibacterial action of ciprofloxacin. Our findings that glutathione gave protection against other fluoroquinolones and not against nonfluoroquinolone antibiotics imply that reactive oxygen species may have a similar role in the antibacterial action of all these fluoroquinolones and that glutathione-mediated protection is not a general phenomenon but specific to fluoroquinolones. These observations are of significance, as fluoroquinolones are important antibiotics with immense therapeutic value, and the effectiveness of treatment by these drugs may be affected by dietary intake and cellular levels of these antioxidants.
Adolescent's Weight Concerns and the Onset of Smoking

The hypothesis that adolescents start smoking because they perceive it as a strategy to control their weight was examined. At the same time, we controlled for sociodemographic, individual, and parental factors. Longitudinal data were collected among 428 Dutch families (mother, father, and two siblings between 13 and 16 years of age) in two measurements: the first in 2002–2003 and the second a year later. Logistic regression analyses supported the hypothesis: weight control motives to smoke were positively related with smoking initiation. The study's limitations and implications are discussed.
Oral lichen planus in relation to transaminase levels and hepatitis C virus.

BACKGROUND Elevation of transaminase levels was reported earlier in patients with oral lichen planus. The association between hepatitis C virus (HCV) and lichen planus had given positive and negative results. The controversies and uncertainties regarding the association of HCV and the liver function status (transaminase levels) in oral lichen planus inspired us to conduct this study. PATIENTS AND METHODS This study was performed on 40 patients with different types of oral lichen planus as a study group and 40 healthy cases as control group. All patients were subjected to routine blood test and urine analysis and the estimation of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) levels. The values of SGOT and SGPT levels < or =40 IU / l were considered within normal limits. Anti-HCV titer was estimated in all cases. RESULTS Fourteen patients (35%) with oral lichen planus had diabetes mellitus, while six (15%) cases of the control group had diabetes mellitus (P = 0.04). Regarding SGOT and SGPT levels, it was elevated in 19 cases (47.5%) and in 4 cases (10%) of the study group and control group, respectively (P = 0.0002). In relation to the type of oral lichen planus, out of 15 erosive cases, 80% (12 cases) showed elevated SGOT/SGPT levels. Out of 25 non-erosive cases, 7 (28%) patients showed elevated SGOT/SGPT levels (P < 0.01). Anti-HCV titer was negative in all cases. CONCLUSION We can conclude that diabetes mellitus and elevated transaminase levels might be related to the development of oral lichen planus lesions. There is a strong association between elevated SGOT/SGPT levels and detection of erosive type of such lesions. However, no correlation between oral lichen planus and HCV infection could be assessed in the present study.
[Procalcitonin for the diagnosis of nosocomial neonatal sepsis].

BACKGROUND Nosocomial sepsis is a major problem in neonatal units. Because the clinical signs are nonspecific, highly reliable diagnostic markers are required to guide diagnosis. The aim of this study was to evaluate the utility of procalcitonin (PCT) as a diagnostic marker for nosocomial neonatal sepsis, and to compare the results of PCT with those of the most widely used laboratory tests for sepsis. PATIENTS AND METHODS Twenty neonates with nosocomial sepsis and 20 controls aged 4-30 days were included in a prospective study performed in a neonatal intensive care unit. PCT, C-reactive protein (CRP), leukocyte count, and the immature-to-total neutrophil ratio (I/T ratio) were measured at onset of signs of infection. The sensitivity, specificity, and likelihood ratio for a positive (LR+) and a negative (LR-) result were calculated. RESULTS PCT, CRP, and the I/T ratio discriminated septic from nonseptic patients. Their areas under the ROC curve were 0.849, 0.880, and 0.884, respectively, with no statistically significant differences. Optimal cut-off values were: PCT > or = 0.65 ng/ml (sensitivity 85 %, specificity 80 %, LR 1 4.25, LR- 0.19), PCR > or = 5 . g/ml (sensitivity 80 %, specificity 95 %, LR 1 16, LR- 0.21), and I/T > or = 0.03 (sensitivity 90 %, specificity 75 %, LR 1 3.6, LR- 0.13). CONCLUSIONS PCT may be a useful marker for the diagnosis of nosocomial neonatal sepsis. Studies with larger samples are required to compare the accuracy of PCT with that of other markers of sepsis.
Randomized comparison of the SLIPA (Streamlined Liner of the Pharynx Airway) and the SS‐LM (Soft Seal Laryngeal Mask) by medical students

Objective: The aim of the study was to compare the Streamlined Liner of the Pharynx Airway (SLIPA; Hudson RCI), a new supraglottic airway device, with the Soft Seal Laryngeal Mask (SS‐LM; Portex) when used by novices.
Trunk performance after stroke and the relationship with balance, gait and functional ability

Objective: To evaluate trunk performance in non-acute and chronic stroke patients by means of the Trunk Control Test and Trunk Impairment Scale and to compare the Trunk Control Test with the Trunk Impairment Scale and its subscales in relation to balance, gait and functional ability after stroke. Subjects: Fifty-one stroke patients, attending a rehabilitation programme, participated in the study. Main measures: Subjects were evaluated with the Trunk Control Test, Trunk Impairment Scale, Tinetti balance and gait subscales, Functional Ambulation Category, 10-m walk test, Timed Up and Go Test and motor part of the Functional Independence Measure. Results: Participants obtained a median score of 61 out of 100 on the Trunk Control Test and 11 out of 23 for the Trunk Impairment Scale. Twelve participants (24%) obtained the maximum score on the Trunk Control Test; no subject reached the maximum score on the Trunk Impairment Scale. Measures of trunk performance were significantly related with values of balance, gait and functional ability. Multivariate linear regression analysis showed an additional, significant contribution of the dynamic sitting balance subscale of the Trunk Impairment Scale in addition to the Trunk Control Test total score for measures of gait and functional ability (model R2 = 0.55-0.62). Conclusions: This study clearly indicates that trunk performance is still impaired in non-acute and chronic stroke patients. When planning future follow-up studies, use of the Trunk Impairment Scale has the advantage that it has no ceiling effect.
CONNECTING TRANSITIONS IN GALAXY PROPERTIES TO REFUELING

We relate transitions in galaxy structure and gas content to refueling, here defined to include both the external gas accretion and the internal gas processing needed to renew reservoirs for star formation. We analyze two z = 0 data sets: a high-quality ∼200 galaxy sample (the Nearby Field Galaxy Survey, data release herein) and a volume-limited ∼3000 galaxy sample with reprocessed archival data. Both reach down to baryonic masses ∼109 M☉ and span void-to-cluster environments. Two mass-dependent transitions are evident: (1) below the “gas-richness threshold” scale (V ∼ 125 km s−1), gas-dominated quasi-bulgeless Sd–Im galaxies become numerically dominant; while (2) above the “bimodality” scale (V ∼ 200 km s−1), gas-starved E/S0s become the norm. Notwithstanding these transitions, galaxy mass (or V as its proxy) is a poor predictor of gas-to-stellar mass ratio Mgas/M*. Instead, Mgas/M* correlates well with the ratio of a galaxy's stellar mass formed in the last Gyr to its preexisting stellar mass, such that the two ratios have numerically similar values. This striking correspondence between past-averaged star formation and current gas richness implies routine refueling of star-forming galaxies on Gyr timescales. We argue that this refueling underlies the tight Mgas/M* versus color correlations often used to measure “photometric gas fractions. ” Furthermore, the threshold and bimodality scale transitions reflect mass-dependent demographic shifts between three refueling regimes—accretion-dominated, processing-dominated, and quenched. In this picture, gas-dominated dwarfs are explained not by inefficient star formation but by overwhelming gas accretion, which fuels stellar mass doubling in ≲1 Gyr. Moreover, moderately gas-rich bulged disks such as the Milky Way are transitional, becoming abundant only in the narrow range between the threshold and bimodality scales.