Miracle-dz/UniFAR-FTUs huggingface dataset:
Azathioprine and 6‐mercaptopurine pharmacogenetics and metabolite monitoring in inflammatory bowel disease

Abstract The thiopurine drugs azathioprine and 6‐mercaptopurine (6‐MP) are well‐established in the treatment of inflammatory bowel disease (IBD). However, there is a wide inter‐ and intra‐patient variation in the concentrations of active and toxic metabolites due to their complex metabolism and genetic polymorphisms in metabolizing enzymes. Serious drug toxicity leads to cessation of therapy in 9–25% of patients, and there is failure to achieve efficacy in approximately 15% of cases. Advances in the understanding of thiopurine drug metabolism have led to new genetic and metabolite tests to help clinicians optimize thiopurine use. Thiopurine methyltransferase (TPMT) enzyme activity can predict life‐threatening myelotoxicity in the one in 300 patients who are TPMT‐deficient. However, myelotoxicity can also occur in the presence of normal TPMT activity so blood count monitoring should remain standard practice. TPMT testing may also aid in dose individualization. 6‐Thioguanine nucleotides (6‐TGN) are thought to be the predominant active metabolites of the thiopurines. 6‐Thioguanine nucleotide concentration is correlated with bone marrow toxicity and may also correlate with efficacy in IBD. Measurement of 6‐TGN and 6‐methylmercaptopurine (6‐MMP) concentration is most useful in determining why a patient is not responding to a standard dose of a thiopurine drug and may help in avoiding myelosuppression. The ratio of these metabolites can help distinguish non‐compliance, under‐dosing, thiopurine‐resistant and thiopurine‐refractory disease. Some of these investigations are entering routine clinical practice but more research is required to determine their optimal use in patients with IBD.
Homocysteine, atherosclerosis and prevalent cardiovascular disease in the elderly: The Rotterdam Study

Bots ML, Launer LJ, Lindemans J, Hofman A, Grobbee DE (Erasmus University Medical School and University Hospital Rotterdam, Rotterdam; Utrecht University, Utrecht; and the National Institute of Public Health, Bilthoven; The Netherlands). Homocysteine, atherosclerosis and prevalent cardiovascular disease in the elderly: The Rotterdam Study. 1997; 242: 339–47.
Online Store Locator: An Essential Resource for Retailers in the 21st Century

Most retailers use their websites and social media to increase their visibility, while potential customers get information about these retailers using the Internet on electronic devices. Many papers have previously studied online marketing strategies used by retailers, but little attention has been paid to determine how these companies provide information through the Internet about the location and characteristics of their stores. This paper aims to obtain evidence about the inclusion of interactive web maps on retailers’ websites to provide information about the location of their stores. With this purpose, the store locator interactive tools of specialty retailers’ websites included in the report “Global Powers of Retailing 2015” are studied in detail using different procedures, such as frequency analysis and word clouds. From the results obtained, it was concluded that most of these firms use interactive maps to provide information about their offline stores, but today some of them still use non-interactive (static) maps or text format to present this information. Moreover, some differences were observed among the search filters used in the store locator services, according to the retailer’s specialty. These results provided insight into the important role of online store locator tools on retailers’ websites.
[Ixodes ricinus, transmitted diseases and reservoirs].

The tick Ixodes ricinus has been recorded in most Italian regions especially in thermo-mesophilous woods and shrubby habitats where the relative humidity allow the tick to complete its 3 year developmental cycle, as predicted for the European climatic ranges. This tick acts both as vector and reservoir for a series of wildlife zoonotic pathogens, especially the agents of Lyme diseases, Tick borne encephalitis and Human Granulocytic Ehrlichiosis, which are emerging in most of Europe. To assess the spatial distribution of these pathogens and the infection risk for humans and animals within the territory of the Province of Trento, we carried out a long term study using a combination of eco-epidemiological surveys and mathematical modelling. An extensive tick collection with a GIS based habitat suitability analysis allowed us to identify the areas where tick occurs at various density. To identify the areas with higher infection risk, we estimated the values of R0 for Borrelia burgdorferi s.l. , TBE virus and Anaplasma phagocytophila under different ecological conditions. We assessed the infection prevalence in the vector and in the wildlife reservoir species that play a central role in the persistence of these infections, ie the small mammals A. flavicollis and C. glareolus. We also considered the double effect of roe deer (Capreolus capreolus) which act as reservoir for A. phagocytophila but is an incompetent host for B. burgdorferi and TBE virus, thus reducing the infection prevalence in ticks of these last two pathogens. Infection prevalence with B. burgdorferi and A. phagocytophila in the vector was assessed by PCR screening 1212 I. ricinus nymphs collected by dragging in six main study areas during 2002. The mean infection prevalence recorded was 1.32% for B. burgdorferi s.l. and 9.84% for A. phagocytophila. Infection prevalence in nymphs with TBE virus, as assessed in a previous study was 0.03%. Infection prevalence in rodents was assessed by screening (with ELISA and PCR) tissues and blood samples collected from 367 rodent individuals trapped extensively during 2002 within 6 main study areas. A. flavicollis (N=238) was found to be infected with all three pathogens investigated, with infection prevalence ranging from 3.3% for TBE virus to 11.7% for A. phagocytophila, and 16.6% with B. burgdorferi s.l. C. glareolus (N=108) showed an infection prevalence of 6.5% with A. phagocytophila and 12.7% with B. burgdorferi s.l. , while no individuals were infected with TBE virus. We also screened 98 spleen samples collected from roe deer with PCR, resulting in a mean prevalence of infection with A. phagocytophila of 19.8%. Using a deterministic model we explored the condition for diseases persistence under different rodent and roe deer densities. R0 values resulted largely above 1 for B. burgdorferi s.l. in the vast majority of the areas classified as suitable for I. ricinus occurrence in Trentino, while the condition for TBE persistence appeared to be more restricted by a combination of climatic condition and host densities.
Implications of Immunohistochemical Detection of C4d along Peritubular Capillaries in Late Acute Renal Allograft Rejection

Background. Immunohistochemical detection of the C4d complement product along peritubular capillaries (PC) may indicate humoral rejection of renal allografts. We examined the frequency of PC C4d expression in renal-allograft biopsies with acute rejection (AR) arising more than 6 months after transplantation and the impact of this finding. Methods. C4d was detected by immunoperoxidase in 2-micron paraffin sections of consecutive biopsies obtained over a 3-year period. The extent was classified as diffuse (≥50% PC C4d+), focal (<50% C4d+), and negative (C4d−). Clinical data were obtained by retrospective chart review. Fifty-five AR episodes with Banff 97 types 1A (n=13), 1B (n=26), 2A (n=11), 2B (n=3), and 3 (n=2) met inclusion criteria. Results. PC C4d expression was diffuse in 23 (42%), focal in 9 (16%), and negative in 23 (42%) biopsies. AR episodes with focal and diffuse C4d expression had higher proportionate elevation of serum creatinine at biopsy and 4 weeks after diagnosis (P≤0.05). Biopsies with diffuse PC C4d had interstitial hemorrhage (56.5%) and plasmacytic infiltrates (52%) more frequently than C4d− biopsies (22% and 16%), P=0.02, but had no other distinctive histologic features. Graft loss was greater in diffuse (65%) compared with focal C4d+ (33%) and C4d− (33%) groups 1 year after diagnosis, P=0.03. Other clinical and pathologic parameters did not differ significantly, including treatment received for AR. Conclusion. Evidence of acute cellular with occult humoral rejection is identified in more than 40% of late AR episodes. Late acute humoral rejection may be associated with interstitial hemorrhage and plasma cells and contributes significantly to graft loss.
The statistical analysis of single-subject data: a comparative examination.

BACKGROUND AND PURPOSE The purposes of this study were to examine whether the use of three different statistical methods for analyzing single-subject data led to similar results and to identify components of graphed data that influence agreement (or disagreement) among the statistical procedures. METHODS Forty-two graphs containing single-subject data were examined. Twenty-one were AB charts of hypothetical data. The other 21 graphs appeared in Journal of Applied Behavioral Analysis, Physical Therapy, Journal of the Association for Persons With Severe Handicaps, and Journal of Behavior Therapy and Experimental Psychiatry. Three different statistical tests--the C statistic, the two-standard deviation band method, and the split-middle method of trend estimation--were used to analyze the 42 graphs. RESULTS A relatively low degree of agreement (38%) was found among the three statistical tests. The highest rate of agreement for any two statistical procedures (71%) was found for the two-standard deviation band method and the C statistic. A logistic regression analysis revealed that overlap in single-subject graphed data was the best predictor of disagreement among the three statistical tests (beta = .49, P < .03). CONCLUSION AND DISCUSSION The results indicate that interpretation of data from single-subject research designs is directly influenced by the method of data analysis selected. Variation exists across both visual and statistical methods of data reduction. The advantages and disadvantages of statistical and visual analysis are described.
Cognitive and adaptive outcome in low-grade pediatric cerebellar astrocytomas: evidence of diminished cognitive and adaptive functioning in National Collaborative Research Studies (CCG 9891/POG 9130).

PURPOSE Clinicians often assume that children with posterior fossa tumors are at minimal risk for cognitive or adaptive deficits if they do not undergo cranial irradiation. However, small case series have called that assumption into question, and have also suggested that nonirradiated cerebellar tumors can cause location-specific cognitive and adaptive impairment. This study (1) assessed whether resected but not irradiated pediatric cerebellar tumors are associated with cognitive and adaptive functioning deficits, and (2) examined the effect of tumor location and medical complications on cognitive and adaptive functioning. PATIENTS AND METHODS The sample was composed of 103 children aged 3 to 18 years with low-grade cerebellar astrocytomas, who underwent only surgical treatment as part of Children's Cancer Group protocol 9891 or Pediatric Oncology Group protocol 9130. The sample was divided into three groups based on primary tumor location: vermis, left hemisphere, or right hemisphere. Data were collected prospectively on intelligence, academic achievement, adaptive skills, behavioral functioning, and pre-, peri-, and postsurgical medical complications. RESULTS The sample as a whole displayed an elevated risk for cognitive and adaptive impairment that was not associated consistently with medical complications. Within this group of children with cerebellar tumors, tumor location had little effect on cognitive, adaptive, or medical outcome. CONCLUSION We did not replicate previous findings of location-specific effects on cognitive or adaptive outcome. However, the elevated risk of deficits in this population runs contrary to clinical lore, and suggests that clinicians should attend to the functional outcomes of children who undergo only surgical treatment for cerebellar tumors.
Bayesian variable selection for disease classification using gene expression data

MOTIVATION An important application of gene expression microarray data is the classification of samples into categories. Accurate classification depends upon the method used to identify the most relevant genes. Owing to the large number of genes and relatively small sample size, the selection process can be unstable. Modification of existing methods for achieving better analysis of microarray data is needed. RESULTS We propose a Bayesian stochastic variable selection approach for gene selection based on a probit regression model with a generalized singular g-prior distribution for regression coefficients. Using simulation-based Markov chain Monte Carlo methods for simulating parameters from the posterior distribution, an efficient and dependable algorithm is implemented. It is also shown that this algorithm is robust to the choices of initial values, and produces posterior probabilities of related genes for biological interpretation. The performance of the proposed approach is compared with other popular methods in gene selection and classification via the well-known colon cancer and leukemia datasets in microarray literature. AVAILABILITY A free Matlab code to perform gene selection is available at http://www.sta. cuhk.edu. hk/xysong/geneselection/. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Geomicrobiology of Deep-Sea Hydrothermal Vents

During the cycling of seawater through the earth's crust along the mid-ocean ridge system, geothermal energy is transferred into chemical energy in the form of reduced inorganic compounds. These compounds are derived from the reaction of seawater with crustal rocks at high temperatures and are emitted from warm (≤25�C) and hot (∼350�C) submarine vents at depths of 2000 to 3000 meters. Chemolithotrophic bacteria use these reduced chemical species as sources of energy for the reduction of carbon dioxide (assimilation) to organic carbon. These bacteria form the base of the food chain, which permits copious populations of certain specifically adapted invertebrates to grow in the immediate vicinity of the vents. Such highly prolific, although narrowly localized, deep-sea communities are thus maintained primarily by terrestrial rather than by solar energy. Reduced sulfur compounds appear to represent the major electron donors for aerobic microbial metabolism, but methane-, hydrogen-, iron-, and manganese-oxidizing bacteria have also been found. Methanogenic, sulfur-respiring, and extremely thermophilic isolates carry out anaerobic chemosynthesis. Bacteria grow most abundantly in the shallow crust where upwelling hot, reducing hydrothermal fluid mixes with downwelling cold, oxygenated seawater. The predominant production of biomass, however, is the result of symbiotic associations between chemolithotrophic bacteria and certain invertebrates, which have also been found as fossils in Cretaceous sulfide ores of ophiolite deposits.
Inertial navigation system positioning error analysis and Cramér-Rao lower bound

Self-contained inertial navigation system (INS) has generated enough attention inside indoor positioning and navigation sector in recent years. However stand-alone low-cost INS suffers severe position drift after using for a short period of time due to the noises in both gyroscope and accelerometer. This paper presents the theoretical analysis of INS's position root mean squared error (RMSE) caused by white Gaussian noise within body frame sensors. Standard deviations of Gaussian noise in tri-axial accelerometer and tri-axial gyroscope are acquired through Allan Variance analysis. Up to second order of Taylor expansion is considered when approximating transformation matrix formed by gyroscope values from beginning, which is used to project acceleration collected from body frame onto local navigation frame. No particular IMU mounting position is assumed for the derivation. In addition, Cramér-Rao Lower Bound (CRLB) for INS perturbed by the same white Gaussian noise is derived for comparison with RMS error on the same route to test our proposed methodology. Monte Carlo simulation is performed to compare with derived RMS error and CRLB. The plot of RMS error is shown to be close to CRLB especially at the early stage of the route. Our proposed RMS error analysis proves to be efficient by staying close to CRLB along the route where CRLB serves as a lower benchmark of position error growth. It can also provide insight of performance for any other INS if the mean and variances of sensors noises are known. In conclusion, the main contribution of this paper is that our proposed position RMS error methodology can serve as an efficient alternative to CRLB.
Interleukin‐6 (IL‐6) and its soluble receptor support survival of sensory neurons

The cytokine interleukin‐6 (IL‐6) has multiple functions in the immune and hematopoietic systems. IL‐6 is related to ciliary neurotrophic factor (CNTF), a trophic factor for motoneurons, sensory dorsal root ganglion (DRG) neurons, and other neuronal subpopulations. Both act via related receptor complexes, consisting of one ligand‐specific α‐receptor subunit (IL‐6R and CNTFR, respectively) and two signal‐transducing receptor components. Even though IL‐6 is expressed by neurons and glia, the functions of IL‐6 in the nervous system are poorly understood. Here, we report that exogenous human IL‐6 promotes the survival of dissociated newborn rat DRG neurons in vitro if supplemented with soluble human IL‐6‐α‐receptor. The dosages of human IL‐6 and soluble human IL‐6R necessary to achieve neurotrophic effects could be reduced markedly by linking ligand and α‐receptor component in a designer cytokine. Furthermore, we show that newborn rat DRG neurons express and secrete bioactive IL‐6. Endogenously secreted IL‐6 does not enhance survival of these neurons in vitro, suggesting that DRG neurons do not sufficiently express cell surface IL‐6R. Exogenously added soluble rat IL‐6R rendered DRG neurons responsive to secreted IL‐6. Our results indicate an autocrine function of IL‐6 in DRG neuron survival which depends on membrane‐bound or soluble IL‐6R as a neurotrophic cofactor. J. Neurosci. Res. 55:411–422, 1999. © 1999 Wiley‐Liss, Inc.
Senile Dementia: a Threshold Phenomenon of Normal Aging?

Neurochemical investigations with normal aging brains show that in the first 70 years of life no major changes of the glycolytic pathway can be observed. Only in the following decades does a significant decrease of brain metabolic turnover occur. Changes in nerve cell size, one of the most relevant parameters in evaluating a diffuse nerve cell atrophy, appear in the brain cortex not earlier than between 85 and 94 years of age; a 21% nerve cell shrinkage is the mean. The results demonstrate that a significant decrease in turnover of the glycolytic pathway is followed by a significant but moderate shrinkage of the nerve cells after a delay of 10-15 years. Similar investigations in brains from senile demented subjects demonstrate that the change in glycolytic turnover is much more a quantitative than a qualitative phenomenon. In comparison with age-matched controls a decrease in glycolytic turnover of more than 60% is observed. Morphometric investigations of the nerve cell sizes in the brain cortex of senile demented subjects showed a decrease of 45-55% when compared with age-matched controls. When normal aging is compared with senile dementia it seems that old age dementia is a threshold phenomenon which starts if the glycolytic turnover drops below 50% of its value in young healthy adults. Physiological aging, however, stays within the range of the reserve capacity of normal brain performance. In conclusion, it seems that the exhaustion of the functional reserve capacity may shift an aging brain into a dementia syndrome.
Adaptation of heart to training: A comparative study using echocardiography & impedance cardiography in male & female athletes

Background & objectives: Intensive regular physical exercise training is associated with a physiological changes in left ventricular (LV) morphology and functions. This cardiac remodeling observed in the athletes is associated with the specific haemodynamic requirements of the exercise undertaken. The main objective of this study is to evaluate the effect of endurance training on cardiac morphology, systolic and diastolic LV functions and haemodynamic parameters both in male and female athletes. Methods: Seventy nine healthy athletes (age 20.0 ± 2.6 yr; 49% male) and 82 healthy sedentary adolescent (age 20.8 ± 2.2 yr, 49% male) volunteered to participate in this study. All subjects underwent transthoracic echocardiography and impedance cardiography. Results: Both female and male athletes had greater LV end-diastolic cavity sizes, LV mass and stroke volume (SV) values when compared with controls. Also, in male athletes, LV mass index was higher than in female athletes. While male athletes had lower resting heart rate compared to female athletes, they had higher mean arterial blood pressure. In male athletes, basal septal and mid septal strain values were higher compared to controls. There were no significant differences in strain and peak systolic strain rate values between female athletes and controls. In male athletes, there was a weak positive correlation between SV and LV mass, basal lateral and septal strain values. In female athletes, only a weak positive correlation was found between SV and basal septal strain values. Interpretation & conclusions: Endurance-trained male and female athletes had higher LV mass, LV cavity dimensions and SV compared to sedentary controls. Although there was no difference in diastolic cardiac functions between athletes and controls, local enhanced systolic function was found with increase of SV. Both morphologic and haemodynamic differences were more evident in male athletes.
Knowledge, attitude and practice of tobacco use and its impact on oral health status of 12 and 15 year-old school children of Chhattisgarh, India.

BACKGROUND Tobacco is a leading preventable cause of deaths worldwide; the situation is particularly serious in the developing countries. Tobacco use amongst the children and adolescents is already a pandemic and they are vulnerable targets of tobacco industry. This is also the case in India. OBJECTIVES 1) Document and monitor the prevalence of tobacco use including smoked, smokeless and other forms of tobacco; 2) Understand studentknowledge and attitudes related to tobacco use and its health impact; 3) Assess the impact of tobacco on the oral health status of school-going children in India. MATERIALS AND METHODS The sample was 1,500 school children of the age group 12-15 years age. A pretested, close ended questionnaire was administered in the form of extensive face to face interview to understand student knowledge, attitudes and behavior related to tobacco use and its health impact and to assess the prevalence of tobacco use including smoked, smokeless and other forms of tobacco. Oral health status was assessed using the Community Periodontal Index (CPI). Frequency distribution, Chi-square tests and Odd's ratio was calculated. RESULTS Prevalence of tobacco usage amongst the prevalence was 20.4%: 9.2% reported smoking, 15.8% used tobacco in the chewable form and 25.3% children were involved in consuming betel nut/areca nuts. The OR (Odd's ratio) for calculus formation was highest for guthka chewers (OR=14.322), paan masala chewers had the highest odds of developing bleeding on probing when compared to the others. CONCLUSIONS There is an urgent need to launch school-based tobacco prevention programs for community awareness of children and the public, as preventing the initiation of a habit is far easier than stopping it.