Miracle-dz/UniFAR-FTUs huggingface dataset:
A Mycobacterium leprae VNTR database.

A great deal of the last quarter of a century’s astonishing progress in understanding and treating human disease is attributable to the existence of public databases where information about DNA sequences, protein sequences, protein structures, human variation, etc. is stored and is freely available to all interested investigators. Information that is developed by one laboratory to help answer a specific question can be combined with, and compared to, similar information from hundreds of other laboratories – information that was developed for hundreds of different, often unrelated, reasons. That process of combining and comparing information is called data mining and is the basis of the successful field of bioinformatics. Once disdained as ‘mere data mining’, it is now well understood that no one laboratory can generate the breadth of information required to gain insight into many key processes related to human diseases. Data that were at one time carefully hoarded by each individual investigator are now freely shared, and all investigators have benefited enormously from that sharing. Indeed, it is now well understood that the application of that information to the practical business of solving human diseases requires that sharing. The recent identification and validation of 16 VNTR (microsatellite) loci in the genome of Mycobacterium leprae has provided a reliable, high-resolution basis for the identification of M. leprae isolates. The method holds the promise of elucidating fundamental information about the epidemiology of M. leprae, including potential sources of infection, the exact mode of transmission, and the potential importance of person-to-person contact. The method is also expected to contribute to our understanding of the basic pathogenesis of the organism, including such matters as the number of organisms required for successful infection, and the time between infection and initial appearance of symptoms of leprosy. A series of eight recent survey studies in six different countries – 10 employed those loci and made clear the value of the VNTR approach and its superiority to earlier approaches to molecular strain typing. Further insight into the global population structure of M. leprae (the division of the global population into clusters of genetically similar strains) and migration of M. leprae between countries, was gained by combining the results of those studies and analysing them as a whole. Combining those results required manually extracting the data from each of the eight papers, a process that was similar to the manual copying of DNA sequences from published papers before
Survival After Primary Prevention Implantable Cardioverter-Defibrillator Placement Among Patients With Chronic Kidney Disease

Background—Guidelines recommend that implantable cardioverter-defibrillator (ICD) candidates have an estimated longevity of ≥1 year. Longevity can be affected by chronic kidney disease (CKD). Methods and Results—Using the National Cardiovascular Data Registry ICD registry linked with the Social Security Death Master File, we assessed the rate of death after primary prevention ICD placement between January 1, 2006, and December 31, 2007, according to CKD stage. Using Cox models, we identified factors associated with death among patients with CKD. Compared with patients without CKD (n=26 056), those with CKD (n=21 226) were older, less commonly men, more often white, and more frequently had comorbid illness. Compared with patients without CKD, patients with a glomerular filtration rate 30 to 60, glomerular filtration rate <30, and end-stage renal disease on dialysis had a higher risk of death after ICD placement (hazard ratio, 2.08; 95% confidence interval, 1.99–2.18; P<0.0001; hazard ratio, 4.20; 95% confidence interval, 3.92–4.50; P<0.0001; and hazard ratio, 4.80; 95% confidence interval, 4.46–5.17; P<0.0001, respectively). Corresponding 1-year death rates were 4.4%, 9.1%, 20.2%, and 22.4%. Among patients with CKD, factors associated with increased risk of death included CKD severity, age >65 years, heart failure symptoms, diabetes mellitus, lung disease, serum sodium <140 mEq/L, atrial fibrillation or flutter, and a lower ejection fraction. Conclusions—The risk of death after primary prevention ICD placement is proportional to CKD severity. Among patients with CKD, several factors are prognostically significant and could inform clinical decision making on primary prevention ICD candidacy.
How to Achieve Informed Consent for Research from Spanish-Speaking Individuals with Low Literacy: A Qualitative Report

Investigators have the responsibility to ensure that prospective participants are fully informed about a research protocol prior to consenting to participate, yet many researchers face challenges when obtaining consent, since the majority of the general population has limited or no familiarity with research studies. These challenges are further magnified when obtaining consent from individuals with low literacy levels and who speak languages other than English. In this article we present findings from a qualitative study conducted with Spanish-speaking individuals with low-literacy designed to refine the Agency for Healthcare Research and Quality's Informed Consent and Authorization Toolkit for Minimal Risk Research. Findings from this study indicate that familiarity with providing informed consent and authorization for research or the experience of being a research participant appear to play key roles in an individual's ability to understand the consent and authorization process. While the text of the consent and authorization documents can be simplified using plain language principles, comprehension of several fundamental ideas such as risk and privacy need to be safeguarded with a consent process that confirms comprehension. Recommendations are provided to address the informational needs of individuals with low literacy levels and limited or no experience with research participation.
Spatial and Temporal Expression of Glucocorticoid, Retinoid, and Thyroid Hormone Receptors Is Not Altered in Lungs of Congenital Diaphragmatic Hernia

The degree of associated pulmonary hypoplasia and persistent pulmonary hypertension are major determination factors for survival in congenital diaphragmatic hernia (CDH) patients. Glucocorticoids, thyroid hormone, and vitamin A have been shown to be involved in human lung development. To determine their therapeutic potential in hypoplastic lungs of CDH patients, the temporal and spatial expression of glucocorticoid receptor, thyroid hormone receptors, retinoic acid receptors, and retinoid X receptors were evaluated in lungs of CDH patients, hypoplastic lungs from other causes, and normal lungs. As a series of supportive experiments, the expressions of these receptors were analyzed in lungs of nitrofen-induced CDH rats. Immunohistochemistry (human and rat) and in situ hybridization (rat) demonstrated no overt difference between CDH, hypoplastic, and control lungs, either in the localization nor the timing of the first expression of all analyzed receptors. The mRNA expression of each receptor was detected in all human CDH lungs by quantitative PCR. Our results suggest that, as far as receptors are concerned, hypoplastic lungs of fetuses and newborns with CDH are potentially as responsive to glucocorticoids, thyroid hormone, and retinoic acid as the lungs of normal children.
Hippocampal volume as an index of Alzheimer neuropathology: Findings from the Nun Study

ObjectiveTo determine whether hippocampal volume is a sensitive and specific indicator of Alzheimer neuropathology, regardless of the presence or absence of cognitive and memory impairment. MethodsPostmortem MRI scans were obtained for the first 56 participants of the Nun Study who were scanned. The area under receiver operating characteristic curves, sensitivity, specificity, and positive and negative predictive values were used to assess the diagnostic accuracy of hippocampal volume in predicting fulfillment of Alzheimer neuropathologic criteria and differences in Braak staging. ResultsHippocampal volume predicted fulfillment of neuropathologic criteria for AD for all 56 participants (p < 0.001): 24 sisters who were demented (p = 0.036); 32 sisters who remained nondemented (p < 0.001), 8 sisters who remained nondemented but had memory impairment (p < 0.001), and 24 sisters who were intact with regard to memory and cognition at the final examination prior to death (p = 0.003). In individuals who remained nondemented, hippocampal volume was a better indicator of AD neuropathology than a delayed memory measure. Among nondemented sisters, Braak stages III and VI were distinguishable from Braak stages II or lower (p = 0.001). Among cognitively intact individuals, those in Braak stage II could be distinguished from those in stage I or less (p = 0.025). ConclusionVolumetric measures of the hippocampus may be useful in identifying nondemented individuals who satisfy neuropathologic criteria for AD as well as pathologic stages of AD that may be present decades before initial clinical expression.
Developing models for future real-time platforms: Virtual simulation and design of new components and systems for aircraft and remotely piloted aircraft systems

In the development of electrified and other vehicle systems, the modelling and simulation of the vehicle is very important. With these tools the preliminary design, as well as later detailed studies of the systems developed, allow engineers to spend less time on each phase of their projects or address them with an integrated approach. In addition, this integrated approach provides the possibility of building hardware-in-the-loop models with all the components required. This vehicle modelling and simulation has gained more interest with the increasing use of a wide variety of RPAS, ranging from light weight micro aircraft to large vehicles of various tons. For this reason, the previously-described building tools are the final objective of the developing models to be used in real-time platform projects. The first step present ed i n this paper is to build a simulator that reproduces the behaviour of a selected aircraft and validate it. This paper presents the study of the performances and behaviour of an OPV used to validate the simulator developed later. At the end, some preliminary tests and estimations of the performances for the selected OPV with an electric motor are presented.
Per capita alcohol consumption and all-cause mortality in Canada, 1950-98.

AIMS To estimate the relationship between per capita alcohol consumption and male all-cause mortality in Canada. DATA AND METHOD The outcome measure comprised annual data on male all-cause mortality for the period 1950-98. Alcohol sales (in litres 100% alcohol) were used as proxy for per capita consumption. The data were analysed using the Box-Jenkins technique. Two models were estimated, one including only female mortality as control, the other in addition cigarette sales. RESULTS The first model yielded a significant alcohol effect that implied a 2.9%[standard error (SE) = 0.6%] increase in mortality given a 1-litre increase in consumption. This estimate coincides with that obtained for northern Europe in previous research. When cigarette sales were included in the model the alcohol effect was still statistically significant but markedly reduced, to 1.7% (SE = 0.6%). CONCLUSIONS Total mortality is a classic indicator of the general health status of the population. Its relationship with per capita consumption of alcohol supports the view that total consumption is a concern for public health.
Breakpoint mapping in a case of mosaicism with partial monosomy 9p23 → pter and partial trisomy 1q41 → qter suggests neo‐telomere formation in stabilizing the deleted chromosome

We report on a clinical and molecular cytogenetic study of a patient who presents a complex chromosomal rearrangement with two different cell lines. Using high‐resolution GTG banding and fluorescence in situ hybridization (FISH) with several probes, including bacterial artificial chromosomes (BACs), the karyotype was defined as 46,XX,del(9)(p23)[54]/46,XX,der(9)t(1;9)(q41;p23)[46], indicating the presence of monosomy 9p23 in all cells and trisomy 1q41 in approximately 50% of the cells. The patient studied presents most of the manifestations of the 9p deletion and 1q duplication syndromes. The breakpoint was mapped at 9p23 with a loss of approximately 13.9‐Mb of DNA. The duplicated segment consists of approximately 35 Mb from 1q41‐qter region. We also suggest that a mechanism for telomere capture and interstitial telomeric sequences (ITs) is involved in a neo‐telomere formation in one of the cell lines. This study highlights the importance of combining high‐resolution chromosome and FISH with BACs in order to make genotype–phenotype correlations and to understand the mechanisms involved chromosomal aberrations. © 2005 Wiley‐Liss, Inc.
Mast cell‐cholinergic nerve interaction in mouse airways

We addressed the mechanism by which antigen contracts trachea isolated from actively sensitized mice. Trachea were isolated from mice (C57BL/6J) that had been actively sensitized to ovalbumin (OVA). OVA (10 μg ml−1) caused histamine release (∼70% total tissue content), and smooth muscle contraction that was rapid in onset and short‐lived (t1/2 < 1 min), reaching approximately 25% of the maximum tissue response. OVA contraction was mimicked by 5‐HT, and responses to both OVA and 5‐HT were sensitive to 10 μm‐ketanserin (5‐HT2 receptor antagonist) and strongly inhibited by atropine (1 μm). Epithelial denudation had no effect on the OVA‐induced contraction. Histological assessment revealed about five mast cells/tracheal section the vast majority of which contained 5‐HT. There were virtually no mast cells in the mast cell‐deficient (sash−/−) mouse trachea. OVA failed to elicit histamine release or contractile responses in trachea isolated from sensitized mast cell‐deficient (sash−/−) mice. Intracellular recordings of the membrane potential of parasympathetic neurons in mouse tracheal ganglia revealed a ketanserin‐sensitive 5‐HT‐induced depolarization and similar depolarization in response to OVA challenge. These data support the hypothesis that antigen‐induced contraction of mouse trachea is epithelium‐independent, and requires mast cell‐derived 5‐HT to activate 5‐HT2 receptors on parasympathetic cholinergic neurons. This leads to acetylcholine release from nerve terminals, and airway smooth muscle contraction.
Frequent deregulation of p16 and the p16/G1 cell cycle‐regulatory pathway in neuroblastoma

Alterations of the p16 gene in neuroblastoma are very rare. Pronounced expression of p16 at both the transcript and protein levels, however, was observed in 7 of 19 (39%) neuroblastoma cell lines and 2 of 6 (33%) primary neuroblastoma samples. As p16 expression is tightly controlled in a feedback loop with Rb, we investigated the possibility that changes in p16 expression were reflective of alterations of the downstream components in the G1 regulatory pathway. Two cell lines and one primary sample highly expressing p16 were shown to harbor CDK4 amplification. The cyclin D2 gene was infrequently expressed in neuroblastoma cell lines and did not correlate with p16 expression. Slight variations in the expression of CDK6, cyclins D1, D3 and E; and E2F1 and E2F2 among the cell lines were observed, without apparent correlation with p16 status. No mutations to the p16‐binding site of CDK4 and CDK6 nor any mutations to the coding region of p16 itself were identified in neuroblastoma cell lines. Despite frequent N‐myc amplification in these cell lines, no relationship with this gene was observed either. All cell lines contained Rb protein with varying degrees of phosphorylation, which bears no correlation with p16 expression. Overall, alterations of the G1 pathway in neuroblastoma included relatively frequent p16 expression and infrequent CDK4 amplification and cyclin D2 expression. Despite a reported feedback relationship between p16 expression and Rb/G1 deregulation, p16 expression in neuroblastoma cell lines is independent of Rb gene and phosphorylation status and, in contrast to other cell lines where expression of p16 leads to G1/S arrest, neuroblastoma cell lines proliferate in the presence of elevated levels of p16. Int. J. Cancer 80:145–154, 1999. © 1999 Wiley‐Liss, Inc.
Economic Growth, Poverty and Inequality Link: Nigerian Experience

While poverty reduction has become the main goal of development efforts, there is an on-going sometimes-heated debate about the elements that should be at the center of the sensible poverty reducing strategy. By definition, poverty reduction in a given country is a function of the changes in average income and changes in income inequality. Rapid and sustained economic growth utilizing a new individual strategy calls for proficient use of the natural advantages of modern infrastructure, which further serves as a poverty reducing strategy. Also the World Bank has argued that a high rate of economic growth is the most effective strategy for reducing poverty. The paper investigated the relative impact of economic growth and changes in equality on poverty. The result of our study showed that both material and social resources do have impact on poverty in Nigeria . The study concluded that there would have been more progress in poverty reduction, particularly in the context of MDGs, if growth had been more equitable than available evidence suggests. In other words, there is room to make growth more pro-poor to enhance rapid reduction in poverty. Keywords: Economic growth, Poverty reduction, Inequality
First episodes of peritoneal infection: description and prognostic factors.

INTRODUCTION Peritonitis is one of the most common and severe complications associated with peritoneal dialysis (PD), constituting the primary cause of catheter loss and exit from the dialysis technique. The incidence and aetiology of peritonitis episodes vary based on geographical region, and change over time. For this reason, it is vital to maintain an updated understanding of the current risk factors and prognostic factors associated with peritonitis. METHOD We performed an observational, multi-centre, prospective cohort study with a maximum follow-up period of 7 years (2003-2010), which included 1177 patients and a total of 476 first episodes of peritonitis (total: 1091 cases of peritonitis). RESULTS We describe the characteristics of the first episode of peritonitis from a large and current study sample. The factors associated with a shorter interval until the first episode of peritonitis as selected by the multivariate analysis included prior cardiovascular comorbidity (Hazard Ratio [HR]: 1.25 [1.04-1.58]), having previously received haemodialysis (HR: 1.39 [1.10-1.76]) or a kidney transplant (HR: 1.38 [1.10-1.93]), having started PD on a manual modality (HR: 1.39 [1.13-1.73]), and initial age >70 years (HR: 1.53 [1.23-1.90]). The first episode of peritonitis was associated with a 7.8% rate of recurrence, an 11.7% rate of catheter removal, and a mortality rate within one month of the episode of 1.3%. The progression of peritonitis infections depended on the type of causal microorganism. We calculated a greater risk for gram-negative bacterial infections (Odds Ratio [OR]: 5.31 [2.26-12.48]) and the aggregate group of infections caused by multiple microorganisms, fungal infections, and mycobacterial infections (OR: 38.24 [13.84-105.63]), as compared to gram-positive bacterial infections. CONCLUSION The development of a first case of peritonitis depends on the characteristics of the patient upon starting dialysis, comorbidities present, and the technique used. Patients at a greater risk for peritonitis must receive special care during training and follow-up.
Normal Tissue Complication Probability (NTCP) modeling of late rectal bleeding following external beam radiotherapy for prostate cancer: A Test of the QUANTEC-recommended NTCP model

Abstract Purpose/background. Validating a predictive model for late rectal bleeding following external beam treatment for prostate cancer would enable safer treatments or dose escalation. We tested the normal tissue complication probability (NTCP) model recommended in the recent QUANTEC review (quantitative analysis of normal tissue effects in the clinic). Material and methods. One hundred and sixty one prostate cancer patients were treated with 3D conformal radiotherapy for prostate cancer at the British Columbia Cancer Agency in a prospective protocol. The total prescription dose for all patients was 74 Gy, delivered in 2 Gy/fraction. 159 3D treatment planning datasets were available for analysis. Rectal dose volume histograms were extracted and fitted to a Lyman-Kutcher-Burman NTCP model. Results. Late rectal bleeding (>grade 2) was observed in 12/159 patients (7.5%). Multivariate logistic regression with dose-volume parameters (V50, V60, V70, etc.) was non-significant. Among clinical variables, only age was significant on a Kaplan-Meier log-rank test (p=0.007, with an optimal cut point of 77 years). Best-fit Lyman-Kutcher-Burman model parameters (with 95% confidence intervals) were: n = 0.068 (0.01, +infinity); m =0.14 (0.0, 0.86); and TD50 = 81 (27, 136) Gy. The peak values fall within the 95% QUANTEC confidence intervals. On this dataset, both models had only modest ability to predict complications: the best-fit model had a Spearman's rank correlation coefficient of rs = 0.099 (p = 0.11) and area under the receiver operating characteristic curve (AUC) of 0.62; the QUANTEC model had rs=0.096 (p= 0.11) and a corresponding AUC of 0.61. Although the QUANTEC model consistently predicted higher NTCP values, it could not be rejected according to the χ2 test (p = 0.44). Conclusions. Observed complications, and best-fit parameter estimates, were consistent with the QUANTEC-preferred NTCP model. However, predictive power was low, at least partly because the rectal dose distribution characteristics do not vary greatly within this patient cohort.
Semi‐volatile organic compounds in the air and dust of 30 French schools: a pilot study

The contamination of indoor environments with chemical compounds released by materials and furniture, such as semi-volatile organic compounds (SVOCs), is less documented in schools than in dwellings-yet children spend 16% of their time in schools, where they can also be exposed. This study is one of the first to describe the contamination of the air and dust of 90 classrooms from 30 nursery and primary schools by 55 SVOCs, including pesticides, phosphoric esters, musks, polycyclic aromatic hydrocarbons (PAHs), polychlorobiphenyls (PCBs), phthalates, and polybromodiphenylethers (PBDEs). Air samples were collected using an active sampling method, and dust samples were collected via two sampling methods (wiping and vacuum cleaning). In air, the highest concentrations (median >100 ng/m3 ) were measured for diisobutyl phthalate (DiBP), dibutyl phthalate (DBP), diethyl phthalate (DEP), bis(2-ethylhexyl) phthalate (DEHP), and galaxolide. In dust, the highest concentrations (median >30 μg/g) were found for DEHP, diisononyl phthalate (DiNP), DiBP, and DBP. An attempt to compare two floor dust sampling methods using a single unit (ng/m²) was carried out. SVOC concentrations were higher in wiped dust, but frequencies of quantification were greater in vacuumed dust.