Miracle-dz/UniFAR-FTUs huggingface dataset:
Spontaneous Vitiligo in an Animal Model for Human Melanoma

Tumor antigen-reactive T cells can be detected in a large proportion of melanoma patients, but their efficacy on tumor control in vivo remains unclear. On the other hand, vitiligo, a skin disorder characterized by patchy depigmented macules, may occur spontaneously or after antitumor therapies. Moreover, vitiligo is significantly associated with positive clinical response, but the mechanism is not understood. Therefore, the establishment of a relevant animal model in which melanoma and vitiligo spontaneously develop stepwise may be useful for better understanding of the parameters involved in the destruction of both benign and malignant melanocytes. In a previous work, we established a mouse model for melanoma in which MT/ret transgenic mice express the ret oncogene fused to the metallothionein promoter. Here we report that melanoma leads to spontaneous vitiligo. We further investigate, for the first time in this model, the natural antitumor T-cell response and evaluate the role of cellular immunity in the development of the disease. Interestingly, the occurrence of spontaneous tumor nodules in MT/ret mice with melanoma-associated vitiligo is significantly delayed when compared in melanoma mice without vitiligo. Moreover, a significant proportion of mice with melanoma-associated vitiligo resisted a challenge with syngeneic melanoma cells in contrast to animals without vitiligo. Our results confirm that vitiligo is associated with clinical benefit and further demonstrate the crucial role of CD8+ T cells for tumor control in melanoma-associated vitiligo.
Anthropometric and metabolic characteristics in children with clinically diagnosed nonalcoholic fatty liver disease.

BACKGROUND Childhood obesity is currently approaching epidemic proportions worldwide. Various chronic diseases are associated with obesity, but nonalcoholic fatty liver disease (NAFLD) has received little attention from paediatricians. AIM To examine anthropometric and metabolic variables relevant to NAFLD disease mechanism and severity. METHODS A retrospective review of 53 consecutive paediatric patients clinically diagnosed with NAFLD was performed between 1997 and 2004. Variables studied included ethnicity, body mass index, acanthosis nigricans, aspartate aminotransferase and alanine amino-transferase levels, and fasting levels of glucose, insulin and lipids. Insulin resistance was quantified by validated models (the homeostasis model of insulin resistance [HOMA-IR] and the quantitative insulin-sensitivity check index [QUICKI]). RESULTS The cohort was comprised of 34 boys and 19 girls; there was a 2:1 male predominance. The mean age of the children was 13.5 years (median 14.2 years; range 5.6 to 18.9 years), and 13 were 11 years of age or younger. Forty-five per cent were Caucasian, 30% Asian and 21% Hispanic. Thirty-eight children (72%) were classified as obese and 11 children (21%) were classified as overweight, with a mean ideal body weight percentage of 150.9+/-4.2 (range 67% to 226%) and a BMI Z score of 1.9+/-0.1 (range -1.2 to 3.2). Hyperinsulinemia was present in 35 children (66%). Insulin resistance (HOMA-IR 9.8+/-2.6, abnormal if greater than 3) was associated with increased plasma triglyceride (P=0.03) and total cholesterol (P=0.04) levels. These parameters were significant irrespective of alanine aminotransferase or aspartate aminotransferase levels. CONCLUSIONS Hyperlipidemia with hyperinsulinemia and insulin resistance in overweight and obese children with fatty liver may be important signs of liver dysfunction in childhood NAFLD, irrespective of serum aminotransferases. In overweight or obese children with hyperlipidemia or insulin resistance, evaluation for NAFLD is warranted.
Infrequent involvement of the anterior base in low-risk patients with clinically localized prostate cancer and its possible significance in definitive radiation therapy.

BACKGROUND The zonal distribution and location of tumors in different subgroups of Japanese patients with clinically localized prostate cancer have not been fully described. The appropriate radiation treatment volume thus remains unclear. METHODS Radical prostatectomy specimens of 141 consecutive patients with clinically localized prostate cancer were examined by the whole organ step-section technique. The zonal distribution and location of tumors at different levels of the gland were investigated after stratification into patient subgroups based on preoperative clinicopathological findings and risk group assessment. RESULTS The median tumor volume was 2.8 cm3; 72 patients (51.1%) had pathologically organ-confined disease (pT2). Higher risk groups showed a statistically significant increase in tumor volume and a decrease in the rate of pathologically confirmed organ confinement. Involvement of the anterior base was found infrequently in certain patient subgroups: in only one of 20 patients (5%) with preoperative PSA <4.0 ng/ml, in three of 19 patients (15.8%) with specimen Gleason scores of 2-4 and in two of 32 patients (6.3%) identified as low-risk. CONCLUSIONS Infrequent involvement of the anterior base in low-risk patients may be an intrinsic feature of clinically localized prostate cancer. Treatment volume modifications in these patients that reduce the radiation dose to the anterior base may be justified to avoid acute and late genitourinary toxicities.
Three-Year Tracking of Fatty Acid Composition of Plasma Phospholipids in Healthy Children

Objectives: The fatty acid composition of plasma phospholipids reflects the dietary fatty acid intake as well as endogenous turnover. We aimed at investigating the potential tracking of plasma phospholipid fatty acid composition in children that participated in a prospective cohort study. Methods: 26 healthy children participated in a longitudinal study on health risks and had been enrolled after birth. All children were born at term with birth weights appropriate for gestational age. Follow-up took place at ages 24, 36 and 60 months. At each time point a 24-hour dietary recall was obtained, anthropometric parameters were measured and a blood sample for phospholipid fatty acid analysis was taken. Results: Dietary intake of saturated (SFA), monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids at the three time points were not correlated. We found lower values for plasma MUFA and the MUFA/SFA ratio at 60 months compared to 24 months. In contrast, total PUFA, total n–6 and n–6 long-chain polyunsaturated fatty acids (LC-PUFA) were higher at 60 months. Significant averaged correlation coefficients (average of Pearson’s R for 24 versus 36 months and 36 versus 60 months) were found for n–6 LC-PUFA (r = 0.67), n–6/n–3 LC-PUFA ratio (r = 0.59) and arachidonic acid/linoleic acid ratio (r = 0.64). Partial tracking was found for the docosahexaenoic acid/α-linolenic acid ratio (r = 0.33). Body mass index and sum of skinfolds Z-scores were similar in the three evaluations. Conclusions: A significant tracking of n–6 LC-PUFA, n–6 LC-PUFA/n–3 LC-PUFA ratio, arachidonic acid/linoleic acid ratio and docosahexaenoic acid/α-linolenic acid ratio may reflect an influence of individual endogenous fatty acid metabolism on plasma concentrations of some, but not all, fatty acids.
Are the Rich Willing to Pay for Beautiful Cities?: Income Effects on the Willingness to Pay for Aesthetic Improvements

This study used the contingent valuation method to measure the amount that Metro Manila households are willing to pay (WTP) for an improvement in urban aesthetic values through the removal of billboards. A household survey was conducted to elicit WTP using the single-bound binary choice format. A measure of income elasticity was used to determine the effects of income on WTP, testing a hypothesis that higher income increases willingness to pay for urban aesthetic improvements. Results of the logistic regressions showed that income is a statistically significant determinant of WTP. Estimates of mean WTP ranged from PHP1,276 (USD29) to PHP1,416 (USD32), while income elasticity was estimated at 1.02 and 1.19, indicating that WTP for urban aesthetic improvements increases more than proportionally as income rises. This implies that programs aimed at improving city aesthetics are valued more by high-income households than low-income households.
Arabidopsis WRKY45 Transcription Factor Activates PHOSPHATE TRANSPORTER1;1 Expression in Response to Phosphate Starvation1[W][OPEN]

Overexpression of a transcription factor enhances Arabidopsis phosphate uptake by activating transporter expression. The WRKY transcription factor family has more than 70 members in the Arabidopsis (Arabidopsis thaliana) genome, and some of them are involved in plant responses to biotic and abiotic stresses. This study evaluated the role of WRKY45 in regulating phosphate (Pi) uptake in Arabidopsis. WRKY45 was localized in the nucleus and mainly expressed in roots. During Pi starvation, WRKY45 expression was markedly induced, typically in roots. WRKY45 overexpression in Arabidopsis increased Pi content and uptake, while RNA interference suppression of WRKY45 decreased Pi content and uptake. Furthermore, the WRKY45-overexpressing lines were more sensitive to arsenate, the analog of Pi, compared with wild-type seedlings. These results indicate that WRKY45 positively regulates Arabidopsis Pi uptake. Quantitative real-time polymerase chain reaction and β-glucuronidase staining assays showed that PHOSPHATE TRANSPORTER1;1 (PHT1;1) expression was enhanced in the WRKY45-overexpressing lines and slightly repressed in the WRKY45 RNA interference line. Chromatin immunoprecipitation and eclectrophoretic mobility shift assay results indicated that WRKY45 can bind to two W-boxes within the PHT1;1 promoter, confirming the role of WRKY45 in directly up-regulating PHT1;1 expression. The pht1;1 mutant showed decreased Pi content and uptake, and overexpression of PHT1;1 resulted in enhanced Pi content and uptake. Furthermore, the PHT1;1-overexpressing line was much more sensitive to arsenate than WRKY45-overexpressing and wild-type seedlings, indicating that PHT1;1 overexpression can enhance Arabidopsis Pi uptake. Moreover, the enhanced Pi uptake and the increased arsenate sensitivity of the WRKY45-overexpressing line was impaired by pht1;1 (35S:WRKY45-18::pht1;1), demonstrating an epistatic genetic regulation between WRKY45 and PHT1;1. Together, our results demonstrate that WRKY45 is involved in Arabidopsis response to Pi starvation by direct up-regulation of PHT1;1 expression.
The association of transfusion status with antioxidant enzymes and malondialdehyde level in Nigerians with sickle cell disease

Background: Sickle cell disease (SCD) often leads to chronic hemolytic anemia of varying severity, and blood transfusion may be employed in the management of SCD complications. Objective: The aim of the study was to evaluate the effect of blood transfusion on the activities of some antioxidant enzymes as well as lipid peroxide and to relate transfusion status to these enzymes and malondialdehyde (MDA) in SCD patients. Materials and Methods: Glutathione peroxidase (GPX), superoxide dismutase, catalase, MDA, and lipoproteins were assayed in 87 SCD and 20 age- and sex-matched subjects with normal hemoglobin. Of the 87 SCD patients, 30 had multiple transfusions, 21 had been transfused once while 36 had not been transfused within the last 3 months. Results: Statistically significant decrease in the mean levels of GPX (P = 0.045) and Cu/Zn SOD (P = 0.001) and increased (P = 0.001) MDA were observed in the transfused compared to non-transfused patients. Similarly, significant decrease (P = 0.001) in Cu/Zn SOD and increase (P = 0.01) in MDA were observed in multi transfused compared to those who had been transfused once. Transfusion status correlated (P <0.047) inversely with Cu/Zn SOD and positively with MDA. Conclusion : Reduced activity levels of serum antioxidant enzymes and increased mean levels of MDA were observed in transfused compared to non-transfused SCD patients and these changes correlated with transfusion status.
Reduced Abundance and Subverted Functions of Proteins in Prion-Like Diseases: Gained Functions Fascinate but Lost Functions Affect Aetiology

Prions have served as pathfinders that reveal many aspects of proteostasis in neurons. The recent realization that several prominent neurodegenerative diseases spread via a prion-like mechanism illuminates new possibilities for diagnostics and therapeutics. Thus, key proteins in Alzheimer Disease and Amyotrophic lateral sclerosis (ALS), including amyloid-β precursor protein, Tau and superoxide dismutase 1 (SOD1), spread to adjacent cells in their misfolded aggregated forms and exhibit template-directed misfolding to induce further misfolding, disruptions to proteostasis and toxicity. Here we invert this comparison to ask what these prion-like diseases can teach us about the broad prion disease class, especially regarding the loss of these key proteins’ function(s) as they misfold and aggregate. We also consider whether functional amyloids might reveal a role for subverted protein function in neurodegenerative disease. Our synthesis identifies SOD1 as an exemplar of protein functions being lost during prion-like protein misfolding, because SOD1 is inherently unstable and loses function in its misfolded disease-associated form. This has under-appreciated parallels amongst the canonical prion diseases, wherein the normally folded prion protein, PrPC, is reduced in abundance in fatal familial insomnia patients and during the preclinical phase in animal models, apparently via proteostatic mechanisms. Thus while template-directed misfolding and infectious properties represent gain-of-function that fascinates proteostasis researchers and defines (is required for) the prion(-like) diseases, loss and subversion of the functions attributed to hallmark proteins in neurodegenerative disease needs to be integrated into design towards effective therapeutics. We propose experiments to uniquely test these ideas.
Immortalization of Human Urethral Epithelial Cells: a Model for the Study of the Pathogenesis of and the Inflammatory Cytokine Response to Neisseria gonorrhoeae Infection

ABSTRACT The primary human urethral epithelial cells developed by our laboratory have been immortalized by transduction with a retroviral vector expressing the human papillomavirus E6E7 oncogenes. Analysis of telomerase expression and comparison to that in primary cells revealed detectable levels in the transduced human urethral epithelial cells. Immortalized urethral cells could be passaged over 20 times. Immunofluorescence microscopy studies showed that the immortalized cells were phenotypically similar and responded to gonococcal infection similarly to primary cells. Specifically, positive cytokeratin staining showed that the immortalized cells are keratinocytes; cell surface levels of human asialoglycoprotein receptor increase following gonococcal infection, and, like the primary cells, the immortalized urethral epithelial cells are CD14 negative. Using enzyme-linked immunosorbent assay, we found that interleukin-6 (IL-6) and IL-8 levels in primary urethral epithelial cell supernatants increase after challenge with N. gonorrhoeae. Likewise, the immortalized urethral epithelial cells produced higher levels of IL-6 and IL-8 cytokines in response to gonococcal infection. Cells challenged with a gonococcal lipid A msbB mutant produced reduced IL-6 and IL-8 levels when compared to the parent strain. Additionally, these data suggest that the 1291 msbB lipooligosaccharide may suppress cytokine induction.
[Validation of a liquid chromatography method for rifampicin determination in human plasma].

OBJECTIVES To validate the high-performance liquid chromatography method (HPLC) for rifampicin (RFP) determination in human plasma. MATERIALS AND METHODS A HPLC method for RFP determination in plasma was developed. The separation was performed by reversed-phase chromatography with C18 column and a mobile phase composed of a mixture of acetonitrile and monobasic potassium phosphate buffer solution 0.05 M (38:62 v/v) at 335 nm in which standard rifampicin quinone (RFP-QN) was used. RESULTS The retention times of RFP and RFP-QN were 7.81 and 12.26 minutes, respectively. The trial was linear from 0.5 to 250 ug/mL. The evaluated parameters of precision, accuracy, selectivity, linearity, and recovery complied with the established international standards for validation of bioanalytical methods. CONCLUSIONS The developed HPLC method is simple, specific, sensitive, selective and linear for a wide range of RFP concentrations in plasma.
A self-lysis pathway that enhances the virulence of a pathogenic bacterium

Significance The programmed cell death (PCD) of mammalian cells plays important roles in fighting bacterial infections. Relatively little is known about the adaptive role of PCD in bacteria. Here we report the discovery of a potential PCD pathway in Pseudomonas aeruginosa. We show that activation of the system can occur in a subset of cells in response to DNA damage through cleavage of an essential transcription regulator that controls a cell lysis program. Although this is lethal to the individual cell in which it occurs, we find that PCD enhances the ability of the bacterium to cause disease. Our findings suggest that PCD is a strategy used by both host and pathogen to promote survival during an infection. In mammalian cells, programmed cell death (PCD) plays important roles in development, in the removal of damaged cells, and in fighting bacterial infections. Although widespread among multicellular organisms, there are relatively few documented instances of PCD in bacteria. Here we describe a potential PCD pathway in Pseudomonas aeruginosa that enhances the ability of the bacterium to cause disease in a lung infection model. Activation of the system can occur in a subset of cells in response to DNA damage through cleavage of an essential transcription regulator we call AlpR. Cleavage of AlpR triggers a cell lysis program through de-repression of the alpA gene, which encodes a positive regulator that activates expression of the alpBCDE lysis cassette. Although this is lethal to the individual cell in which it occurs, we find it benefits the population as a whole during infection of a mammalian host. Thus, host and pathogen each may use PCD as a survival-promoting strategy. We suggest that activation of the Alp cell lysis pathway is a disease-enhancing response to bacterial DNA damage inflicted by the host immune system.
Efficacy of straight versus angled interdental brushes on interproximal tooth cleaning: a randomized controlled trial.

BACKGROUND To investigate interproximal biofilm reduction with an angled interdental brush as compared to a straight interdental brush (standard control) in a clinical, single-centre, single-blind, controlled, parallel-group trial. METHODS Recruitment and examinations of the subjects were performed at the Witten/Herdecke University School of Dental Medicine. 128 volunteers, aged 20-65 years, were recruited and stratified according to sex and age. Two groups with 64 subjects each used either straight (standard control) or angled (test group) handgripped interdental toothbrushes of the same bristle stiffness. After a 12-day home-care habituation period, participants received a professional tooth cleaning followed by a 48-h plaque regrowth period. At the intervention appointment, plaque was recorded with a fluorescent revelator and soft tissue damage was noted (T0 ). Interdental brushing was performed by the participant for 2 min, and clinical parameters were recorded again (T1 ). The primary efficacy end point was the difference in modified Proximal Plaque Index (mPPI) after brushing compared to baseline. Secondary efficacy end points were mPPI differences in subgroups (anterior vs. posterior teeth; vestibular vs. oral tooth surfaces). Safety end point was the Danser gingival abrasion index (DI). RESULTS mPPI showed lower scores after brushing within all (sub)groups (P < 0.01). mPPI brushing efficacy (ΔT0 - T1 ) in subjects using straight interdental brushes was significantly higher as compared to angled interdental brushes (P < 0.0001). Straight interdental brushes were significantly more effective in posterior teeth, when used from vestibular and from oral tooth surfaces (P < 0.0001, P < 0.01 and P < 0.0001, respectively). No significant differences were found between the groups in anterior teeth and concerning soft tissue damage. CONCLUSIONS Straight interdental brushes may better remove plaque interproximally when compared to angled interdental brushes.
Efficacy of a novel auto-fluorescence imaging system with computer-assisted color analysis for assessment of colorectal lesions.

AIM To evaluate the efficacy of computer-assisted color analysis of colorectal lesions using a novel auto-fluorescence imaging (AFI) system to distinguish neoplastic lesions from non-neoplastic lesions and to predict the depth of invasion. METHODS From January 2013 to April 2013, consecutive patients with known polyps greater than 5 mm in size who were scheduled to undergo endoscopic treatment at The Jikei University Hospital were prospectively recruited for this study. All lesions were evaluated using a novel AFI system, and color-tone sampling was performed in a region of interest determined from narrow band imaging or from chromoendoscopy findings without magnification. The green/red (G/R) ratio for each lesion on the AFI images was calculated automatically using a computer-assisted color analysis system that permits real-time color analysis during endoscopic procedures. RESULTS A total of 88 patients with 163 lesions were enrolled in this study. There were significant differences in the G/R ratios of hyperplastic polyps (non-neoplastic lesions), adenoma/intramucosal cancer/submucosal (SM) superficial cancer, and SM deep cancer (P < 0.0001). The mean ± SD G/R ratios were 0.984 ± 0.118 in hyperplastic polyps and 0.827 ± 0.081 in neoplastic lesions. The G/R ratios of hyperplastic polyps were significantly higher than those of neoplastic lesions (P < 0.001). When a G/R ratio cut-off value of > 0.89 was applied to determine non-neoplastic lesions, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 83.9%, 82.6%, 53.1%, 95.6% and 82.8%, respectively. For neoplastic lesions, the mean G/R ratio was 0.834 ± 0.080 in adenoma/intramucosal cancer/SM superficial cancer and 0.746 ± 0.045 in SM deep cancer. The G/R ratio of adenoma/intramucosal cancer/SM superficial cancer was significantly higher than that of SM deep cancer (P < 0.01). When a G/R ratio cut-off value of < 0.77 was applied to distinguish SM deep cancers, the sensitivity, specificity, PPV, NPV, and accuracy were 80.0%, 84.4%, 29.6%, 98.1% and 84.1%, respectively. CONCLUSION The novel AFI system with color analysis was effective in distinguishing non-neoplastic lesions from neoplastic lesions and might allow determination of the depth of invasion.