Miracle-dz/UniFAR-FTUs huggingface dataset:
Multicenter Study of the Prevalence of Diabetes Mellitus and Impaired Glucose Tolerance in the Urban Brazilian Population Aged 30–69 yr

OBJECTIVE To assess the prevalence of diabetes and IGT in the urban adult Brazilian population. RESEARCH DESIGN AND METHODS We used a two-stage, multicenter, cross-sectional survey in a random sample of 21,847 individuals aged 30–69 yr from nine large cities. Subjects were first screened by FCG. All positive screenees (FCG ≥ 5.6 mM/L) and every sixth consecutive negative screenee were administered a 75 g OGTT and classified as diabetic, IGT, or normal (nondiabetic) according to WHO recommendations. OGTT findings from the negative screenees were extrapolated to all negative screenees after adjustments for potential biases. RESULTS The overall rates were 7.6 and 7.8% for diabetes and IGT, respectively. Men (7.5%) and women (7.6%) had similar rates of diabetes. Similar rates resulted with whites (7.8%) and nonwhites (7.3%). Diabetes prevalence increased from 2.7% in the 30–39-yr age-group to 17.4% in the 60–69-yr age-group. Diabetes was more prevalent among less educated people, but this difference disappeared after adjusting for age. Family history of diabetes was associated with a twofold increase in diabetes prevalence (12.5 vs. 5.8%); the same increase occurred with obesity (11.6 vs. 5.2%). Undiagnosed diabetes accounted for 46% of the total prevalence. Among previously diagnosed cases, 22.3% were not under treatment, 7.9% were on insulin, 40.7% were on oral agents, and 29.1% were on dietary treatment only. Self-reported diabetes prevalence was 0.1, 3.2, and 11.6% in the age groups < 30, 30–69, and > 70 yr, respectively. CONCLUSIONS The prevalence of diabetes in Brazil is comparable with that of more developed countries, where it is considered a major health problem.
International Oil Market Risk Anticipations and the Cushing Bottleneck: Option-implied Evidence

This paper studies crude oil market integration and spillovers between Brent and WTI oil indexes over the 2006-2019 period. In addition to prices, we estimate time series of model-free option-implied moments to capture forward-looking market views and anticipations of different risk categories. We describe the WTI-Brent equilibrium relationship in prices and in risk expectations measured by implied volatility, skewness, and kurtosis. Using a fractional cointegration model, we find long memory in the price cointegrating vector and in implied moments, implying that persistence of shocks is an important feature of crude oil markets. The evidence supports a differential in implied volatility but not in prices, and suggests equilibrium fragmentation during the Cushing bottleneck period. Analysis of implied moments reveals that Brent and WTI risk anticipations generally share a common equilibrium. Unlike volatility, asymmetric and tail risks are more locally driven, especially during market disruptions such as the Cushing bottleneck, so there is potential for diversifying extreme risks using both indexes.
Systemic Inflammation-Based Biomarkers and Survival in HIV-Positive Subject With Solid Cancer in an Italian Multicenter Study

Background:Recently, some systemic inflammation-based biomarkers have been demonstrated useful for predicting risk of death in patients with solid cancer independently of tumor characteristics. This study aimed to investigate the prognostic role of systemic inflammation-based biomarkers in HIV-infected patients with solid tumors and to propose a risk score for mortality in these subjects. Methods:Clinical and pathological data on solid AIDS-defining cancer (ADC) and non–AIDS-defining cancer (NADC), diagnosed between 1998 and 2012 in an Italian cohort, were analyzed. To evaluate the prognostic role of systemic inflammation- and nutrition-based markers, univariate and multivariable Cox regression models were applied. To compute the risk score equation, the patients were randomly assigned to a derivation and a validation sample. Results:A total of 573 patients (76.3% males) with a mean age of 46.2 years (SD = 10.3) were enrolled. 178 patients died during a median of 3.2 years of follow-up. For solid NADCs, elevated Glasgow Prognostic Score, modified Glasgow Prognostic Score, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and Prognostic Nutritional Index were independently associated with risk of death; for solid ADCs, none of these markers was associated with risk of death. For solid NADCs, we computed a mortality risk score on the basis of age at cancer diagnosis, intravenous drug use, and Prognostic Nutritional Index. The areas under the receiver operating characteristic curve were 0.67 (95% confidence interval: 0.58 to 0.75) in the derivation sample and 0.66 (95% confidence interval: 0.54 to 0.79) in the validation sample. Conclusions:Inflammatory biomarkers were associated with risk of death in HIV-infected patients with solid NADCs but not with ADCs.
Quantitative Priming with Inactivated Pertussis Toxoid Vaccine in the Aerosol Challenge Model

ABSTRACT Serum antibodies to pertussis toxin (PT) have been shown to be protective against severe pertussis disease, although a specific level of anti-PT antibody that correlates with protection has not been demonstrated. Current animal models such as the intracerebral challenge model have significant limitations in correlating protection to a specific level of anti-PT antibody. This study examines the protective effects of priming with tetranitromethane-inactivated pertussis toxoid (PTx) vaccine in the aerosol challenge model and whether a measurable response to a priming dose of PTx is enough to initiate a protective secondary response when challenged with infection. The correlation of priming with markers of illness such as leukocytosis, weight loss, bacterial proliferation, and mortality after established infection with Bordetella pertussis was explored. BALB/c mice were immunized with PTx vaccine on day 6 of life and then challenged with B. pertussis using the aerosol challenge model. Data were analyzed according to the primary immunologic response, differentiating responders (anti-PT immunoglobulin G [IgG] ≥1 μg/ml) from nonresponders (anti-PT IgG <1 μg/ml). Mice that showed evidence of priming on the day of aerosol challenge were able to mount a secondary response to the challenge with a ≥2-fold rise in anti-PT IgG antibody by day 7 and a ≥10-fold rise by day 14 post-aerosol challenge. These primed mice were significantly better protected against leukocytosis, weight loss, and proliferation of B. pertussis in the lungs following aerosol challenge than the nonprimed group. This protection correlated with levels of anti-PT antibody in serum present on the day of aerosol challenge.
Distribution of photosensitizers in bladder cancer spheroids: implications for intravesical instillation of photosensitizers for photodynamic therapy of bladder cancer.

PURPOSE Uniform intratumor distribution of sufficient photosensitizer is one of the important aspects of photodynamic therapy for solid tumors. METHODS Multicellular spheroids derived from a human transitional cell carcinoma cell line (MGHU3) were used as a surrogate system of tiny solid tumors to study intratumor distribution of photosensitizers. Photosensitizers included Photofrin, hypocrellins (HBEA-R1/R2, HBBA-R2), aluminum phthalocyanine chloride (AlPC), benzoporphyrin derivative monoacid ring A (BPD-MA), protoporphyrin-IX (PpIX), and liposomal formulations of HBBA-R2 and BPD-MA. Spheroids were incubated with various doses of the above drugs for 1-4 hours, and were examined by confocal microscopy. RESULTS Histology showed all cells were healthy in spheroids less than 400 microm in diameter. Scanning electron microscopy showed tight cell-to-cell interdigitation in spheroids. HBEA-R1/R2 distributed more uniformly in spheroids than other drugs. Free hypocrellins and BPD-MA penetrated spheroids centripetally deeper than AlPC, Photofrin, and PpIX. Liposomal HBBA-R2 and BPD-MA penetrated less than their free formulations. CONCLUSIONS The spheroids mimic solid tumors prior to neovascularization. Based on drug distribution in spheroids, hypocrellins and BPD-MA appear superior to Photofrin, AlPC and PpIX for intravesical administration for bladder cancer phototherapy.
Genetic susceptibility to obsessive‐compulsive hoarding: the contribution of neurotrophic tyrosine kinase receptor type 3 gene 1

Recent work suggests that neurotrophic factors may contribute to the genetic susceptibility to obsessive–compulsive disorder (OCD). Among other clinical dimensions, the presence of hoarding obsessions and compulsions has been shown to be correlated with a number of clinical and neuroimaging findings, as well as with a different pattern of genetic inheritance. We used a linkage disequilibrium (LD)‐mapping approach to investigate whether neurotrophic tyrosine kinase receptor type 3 (NTRK3), the high‐affinity receptor of neurotrophin 3 (NT‐3), plays a role in increasing susceptibility to hoarding in OCD. We performed an association study of 52 tag single nucleotide polymorphisms (tagSNPs) covering the whole NTRK3 gene in a sample comprising 120 OCD patients and 342 controls. Single nucleotide polymorphism association and haplotype analysis were performed. Thirty‐six of our patients (30%) exhibited significant hoarding obsessions and compulsions. A significant association of two SNPs in the 3′ downstream region of NTRK3 gene and obsessive–compulsive hoarding was identified: rs1017412 [odds ratio (OR) = 2.16; P = 0.001] and rs7176429 (OR = 2.78; P = 0.0001), although only the latter remained significant after Bonferroni correction. Although the haplotype analysis did not show significant results, a more extended block of LD in the OCD hoarders with respect to the control group was observed, suggesting a lower haplotype diversity in these individuals. Our findings suggest that NTRK3 may contribute to the genetic susceptibility to hoarding in OCD and may constitute an interesting gene to focus on in studies of the genetic basis of obsessive–compulsive hoarding.
A Review of Twenty Congenital Cholesteatomas of the Middle Ear in Children

Cholesteatomas, arising within the middle ear space behind an intact tympanic membrane, have been detected more frequently in recent years. This article reviews 19 children (with a mean age of 4.3 years) who underwent surgery over a 7-year period for removal of cholesteatomas from behind intact tympanic membranes. Most of these children were referred by pediatricians who had detected an asymptomatic whitish middle ear mass. Many had histories of treatment for otitis media. Patients with similar histories were excluded from the series if there had been a prior perforation, myringotomy, or otologic surgery. In the series, one fourth of the children had associated congenital malformations, and there were 3 times as many boys as girls. In two thirds of the cases, the cholesteatoma was manifested as an anterior-superior middle ear mass that seemed to arise from the processus cochleariformis, undersurface of malleus area. Many could be removed via an extended anterior tympanotomy operative approach. The results of surgery are reviewed. The possible origins of these localized cholesteatomas are considered. Are they congenital defects that arise from misplaced keratinizing epithelium? Do they arise from mesenchymal cells whose differentiation is stimulated by inflammatory changes within the middle ear?
Genetic Screens in Human Cells Using the CRISPR-Cas9 System

Improving Whole-Genome Screens Improved methods are needed for the knockout of individual genes in genome-scale functional screens. Wang et al. (p. 80, published online 12 December) and Shalem et al. (p. 84, published online 12 December) used the bacterial CRISPR/Cas9 system to power-screen protocols that avoid several of the pitfalls associated with small interfering RNA (siRNA) screens. Genome editing by these methods completely disrupts target genes, thus avoiding weak signals that can occur when transcript abundance is partially decreased by siRNA. Furthermore, gene targeting by the CRISPR system is more precise and appears to produce substantially fewer off-target effects than existing methods. Genome-editing technology allows improved positive or negative selection screens. The bacterial clustered regularly interspaced short palindromic repeats (CRISPR)–Cas9 system for genome editing has greatly expanded the toolbox for mammalian genetics, enabling the rapid generation of isogenic cell lines and mice with modified alleles. Here, we describe a pooled, loss-of-function genetic screening approach suitable for both positive and negative selection that uses a genome-scale lentiviral single-guide RNA (sgRNA) library. sgRNA expression cassettes were stably integrated into the genome, which enabled a complex mutant pool to be tracked by massively parallel sequencing. We used a library containing 73,000 sgRNAs to generate knockout collections and performed screens in two human cell lines. A screen for resistance to the nucleotide analog 6-thioguanine identified all expected members of the DNA mismatch repair pathway, whereas another for the DNA topoisomerase II (TOP2A) poison etoposide identified TOP2A, as expected, and also cyclin-dependent kinase 6, CDK6. A negative selection screen for essential genes identified numerous gene sets corresponding to fundamental processes. Last, we show that sgRNA efficiency is associated with specific sequence motifs, enabling the prediction of more effective sgRNAs. Collectively, these results establish Cas9/sgRNA screens as a powerful tool for systematic genetic analysis in mammalian cells.
Targeting chaperones in transformed systems – a focus on Hsp90 and cancer

The molecular chaperone Hsp90 is a protein with important roles in maintaining the functional stability and viability of cells under a transforming pressure. Cancer cells harbour mutated oncogenic proteins or proteins with dysregulated function and the chaperone is required to maintain their folded and functionally active conformation. In addition, by chaperoning key proteins such as Raf-1, Akt, survivin and hTERT, Hsp90 regulates signalling pathways necessary for the growth, survival and limitless replicative potential of most tumours. Important elements of the apoptotic pathways are also regulated by Hsp90. Overall, these characteristics propose Hsp90 as an important target of whose inhibition may aim at a wide-range of oncogenic transformations. Several years into Hsp90 research have shed light into the feasibility, but also the limitations, of such an approach. In this review, the authors present the current understanding on the relevance and possibility of translating Hsp90 inhibitors into therapeutic agents in cancer therapy.
Switch of HLA‐G alternative splicing in a melanoma cell line causes loss of HLA‐G1 expression and sensitivity to NK lysis

Considerable information has been accumulated on HLA‐G expression in tumor lesions in which HLA‐G is viewed as a way to turn off anti‐tumoral immunity. Nevertheless, there is little data concerning the mechanisms by which expression and function of HLA‐G are regulated in malignant cells. Here, we have addressed these points by studying a melanoma cell line derived from a surgically‐removed HLA‐G‐positive melanoma lesion. We show that HLA‐G expression in melanoma cells can be regulated at the mRNA splicing level. Indeed, melanoma cells rapidly switched from cell‐surface HLA‐G1 to intra‐cellular HLA‐G2 expression. This mechanism restored tumor sensitivity to NK lysis. Moreover, switch from HLA‐G1 to HLA‐G2 was strong enough to prevent re‐expression of immunoprotective HLA‐G1 even following treatments with cytokines and DNA demethylating agent. Modulating HLA‐G at the mRNA splicing level would be an efficient way of lifting in vivo HLA‐G‐mediated tumor immune escape. © 2005 Wiley‐Liss, Inc.
Binding of (-)-epigallocatechin-3-gallate to the Hsp70 ATPase domain may promote apoptosis in colorectal cancer

Colorectal cancer (CRC) patients frequently have a poor prognosis because of metastases and drug resistance. Heat-shock protein 70 (Hsp70) over-expression in cancer may exacerbate these factors by inhibiting apoptosis, thus providing a potential therapeutic target. The green tea flavonoid (-)-epigallocatechin-3-gallate (EGCG) induces apoptosis in numerous cancer cell lines by unclear mechanisms. This study proposed and investigated a novel mechanism by which EGCG might inhibit the anti-apoptotic activity of Hsp70, namely, by competing with adenosine triphosphate (ATP) for binding to the Hsp70 ATPase domain. It also examined the impact of EGCG on the CRC cell line HT-29, which is known to over-express Hsp70. HT-29 cells were treated with 10–300 mM EGCG for 8, 24 and/or 48 h, then analysed using an MTS proliferation-assay or flow cytometry with Annexin V-FITC and propidium iodide. The competitive binding of EGCG to the Hsp70 ATPase domain was assessed using ATP-agarose, a dot blot and chemiluminescence techniques. EGCG significantly (P, 0.001) and dose-dependently inhibited HT-29 cell viability. Viability was inhibited by 50% (IC50) at 89 mM and 74 mM after 24and 48-h treatments, respectively, also suggesting a time-dependent effect. Apoptosis was induced both doseand timedependently, commencing at 50 mM after 8and 24-h treatments. Further, apoptosis correlated significantly (P, 0.01) with reduced viability as measured by MTS at 24 h, indicating 98% causality. The dot blot suggested 200 mM EGCG competed with ATP for binding to Hsp70, presumably by binding its ATPase domain, theoretically implying this flavonoid could inhibit the anti-apoptotic effect of Hsp70.
Sex differences in the association of regional fat distribution with the severity of obstructive sleep apnea.

STUDY OBJECTIVES To describe sex differences in the associations between severity of obstructive sleep apnea (OSA) and measures of obesity in body regions defined using both dual-energy absorptiometry and traditional anthropometric measures in a sleep-clinic sample. DESIGN A prospective case-series observational study. SETTING The Western Australian Sleep Health Study operating out of the Sir Charles Gairdner Hospital Sleep Clinic, Perth, Western Australia. PARTICIPANTS Newly referred clinic patients (60 men, 36 women) suspected of having OSA. INTERVENTIONS N/A. MEASUREMENTS AND RESULTS Obstructive sleep apnea severity was defined by apnea-hypopnoea index from laboratory-based overnight polysomnography. Body mass index, neck, waist and hip circumference, neck-to-waist ratio, and waist-to-hip ratio were measured. Dual energy absorptiometry measurements included percentage fat and lean tissue. Multivariate regression models for each sex were developed. In women, percentage of fat in the neck region and body mass index together explained 33% of the variance in apnea-hypopnea index. In men, percentage of fat in the abdominal region and neck-to-waist ratio together accounted for 37% of the variance in apnea-hypopnea index. CONCLUSIONS Regional obesity is associated with obstructive sleep apnea severity, although differently in men and women. In women, a direct influence of neck fat on the upper airway patency is implicated. In men, abdominal obesity appears to be the predominant influence. The apnea-hypopnea index was best predicted by a combination of Dual Energy Absorptiometry-measured mass and traditional anthropometric measurements.
Gait parameters identification using video tracking — Case study

In studies so far have been shown that clinical analysis of the gait parameters is extremely important for improving diagnostics and following illness or deficiencies of lower extremities, as well as for analyzing recuperation levels after therapy. Purpose of this paper is to analyze possibility of using easily affordable web cameras for recording knee movement. Recordings are made with web cam on Fujitsu lifebook E laptop. Algorithm for object tracking is made in programming environment MatLAB. Five participants have participated in this research. Results are graphically presented for left and right leg for one gait cycle along straight line and values for anterior posterior (AP) translation are shown in tables for every phase of gait cycle. Acquired study results show that it is possible to measure observed parameter in this way and that values correspond with values obtained in previous studies.
Physical mapping of chromosomes VII and XV of Saccharomyces cerevisiae at 3·5 kb average resolution to allow their complete sequencing

The high resolution complete physical maps of chromosomes VII and XV were constructed to form the basis for sequencing these chromosomes as part of the European systematic sequencing programme of the yeast genome, using a unique cosmid library from strain FY1679, and an original top‐down mapping strategy involving I‐Sce I chromosome fragmentation. A total of 138 and 196 cosmid clones were used to construct the maps for VII and XV, respectively, forming two unique contigs that cover the entirety of chromosomes (1091 kb each), except the telomeric repeats. Colinearity of the cosmid inserts with yeast DNA was verified, and the physical maps were eventually compared with the independently generated genetic maps. © 1998 John Wiley & Sons, Ltd.
Evolution of the response to levodopa during the first 4 years of therapy

The short‐duration response, long‐duration response, and dyskinetic response to levodopa change during long‐term levodopa therapy. How these responses evolve, and which changes contribute to the emergence of motor fluctuations, remain unclear. We studied 18 subjects with Parkinson's disease before they began levodopa therapy and after 6, 12, 24, and 48 months of long‐term levodopa therapy. The responses to 2‐hour levodopa infusions after overnight and after 3 days of levodopa withdrawal were studied from 6 months onward. The mean magnitude of the short‐duration response and the long‐duration response measured after overnight without antiparkinsonian medications did not change during the 4 years. However, after 3 days without levodopa, it was apparent that the short‐duration‐response magnitude was progressively increasing (p < 0.0001) and that the long‐duration response was decaying more rapidly (p = 0.0004). The short‐duration‐response magnitude at 4 years was inversely related to the long‐duration‐response magnitude (p = 0.022), suggesting that the long‐duration response was one determinant of the short‐duration‐response magnitude. Dyskinesia increased progressively in severity during the study (p = 0.013). The duration of the short‐duration response and dyskinesia did not change during the 4 years. Subject reports of motor fluctuations tended to be associated with a large short‐duration response (p = 0.054). We suggest that a larger long‐duration response, rather than a shortened one, is more important to the development of fluctuations. Improving the baseline or practical‐off motor function to reduce the magnitude of the short‐duration response may be a strategy to treat fluctuations.