Miracle-dz/UniFAR-FTUs huggingface dataset:
Empirical Hierarchical Bayes Approach to Gene‐Environment Interactions: Development and Application to Genome‐Wide Association Studies of Lung Cancer in TRICL

The analysis of gene‐environment (G × E) interactions remains one of the greatest challenges in the postgenome‐wide association studies (GWASs) era. Recent methods constitute a compromise between the robust but underpowered case‐control and powerful case‐only methods. Inferences of the latter are biased when the assumption of gene‐environment (G‐E) independence in controls fails. We propose a novel empirical hierarchical Bayes approach to G × E interaction (EHB‐GE), which benefits from greater rank power while accounting for population‐based G‐E correlation. Building on Lewinger et al.'s ([2007] Genet Epidemiol 31:871–882) hierarchical Bayes prioritization approach, the method first obtains posterior G‐E correlation estimates in controls for each marker, borrowing strength from G‐E information across the genome. These posterior estimates are then subtracted from the corresponding case‐only G × E estimates. We compared EHB‐GE with rival methods using simulation. EHB‐GE has similar or greater rank power to detect G × E interactions in the presence of large numbers of G‐E correlations with weak to strong effects or only a low number of such correlations with large effect. When there are no or only a few weak G‐E correlations, Murcray et al.'s method ([2009] Am J Epidemiol 169:219–226) identifies markers with low G × E interaction effects better. We applied EHB‐GE and competing methods to four lung cancer case‐control GWAS from the Interdisciplinary Research in Cancer of the Lung/International Lung Cancer Consortium with smoking as environmental factor. A number of genes worth investigating were identified by the EHB‐GE approach.
Fast and effective quantification of symmetry in medical images for pathology detection: Application to chest radiography

Purpose Symmetry is an important feature of human anatomy and the absence of symmetry in medical images can indicate the presence of pathology. Quantification of image symmetry can then be used to improve the automatic analysis of medical images. Methods A method is presented that computes both local and global symmetry in 2D medical images. A symmetry axis is determined to define for each position p in the image a mirrored position Symbol on the contralateral side of the axis. In the neighborhood of Symbol, an optimally corresponding position Symbol is determined by minimizing a cost function d that combines intensity differences in a patch around p and the mirrored patch around Symbol and the spatial distance between Symbol and Symbol. The optimal value of d is used as a measure of local symmetry s. The average of all values of s, indicated as S, quantifies global symmetry. Starting from an initial approximation of the symmetry axis, the optimal orientation and position of the axis is determined by greedy minimization of S. Symbol. No caption available. Symbol. No caption available. Symbol. No caption available. Symbol. No caption available. Symbol. No caption available. Symbol. No caption available. Results The method was evaluated in three experiments concerning abnormality detection in frontal chest radiographs. In the first experiment, global symmetry S was used to discriminate between 174 normal images and 174 images containing diffuse textural abnormalities from the publicly available CRASS database of tuberculosis suspects. Performance, measured as area under the receiver operating characteristic curve Symbol was 0.838. The second experiment investigated whether adding the local symmetry s as an additional feature to a set of 106 texture features resulted in improvements in classifying local patches in the same image database. We found that Symbol increased from 0.878 to 0.891 (P = 0.001). In the third experiment, it was shown that the contrast of pulmonary nodules, obtained from the publicly available JSRT database, increased significantly in the local symmetry map compared to the original image. Symbol. No caption available. Symbol. No caption available. Conclusions We conclude that the proposed algorithm for symmetry computation provides informative features which can be used to improve abnormality detection in medical images both at a local and a global level.
EFFICIENT AND PRIVACY-AWARE DATA AGGREGATION IN MOBILE SENSING

Mobile phones especially smart phones are getting more and more importance in day to day life. More of these mobile phones are now facilitated with number of applications that are using sensors. With the help of large no. of individual participants, aggregation which is computed from data is really useful and helps to predict the statistics of result. Aggregation guarantees more privacy of the data from individual participants. This paper provides a solution for preserving the individual participants privacy by using aggregate function like Sum, Min. Calculation of Sum aggregation is done without releasing the participant’s information. Min aggregation is calculated using Sum aggregation. Min aggregation is nothing but minimum value of data. In this paper, a multi-hop network is considered where, there is a main aggregator at the highest level and mobile nodes are considered at lowest level and in between node sink is used at middle level. This system deals with dynamic leaves and joins in mobile sensing using the timestamp of the participants.
Genitourinary tuberculosis: a profile of 55 in-patients.

OBJECTIVE To outline the pattern and trends in major cases of genito-urinary tuberculosis (GUTB) which require hospital treatment. METHOD We retrospectively reviewed 55 patients with proven GUTB who were treated as in-patients in a major referral hospital in Pakistan. RESULTS The male/female ratio was 3:1. Prevailing symptoms were lower urinary tract symptoms, flank pain, gross hematuria and fever. A urine culture was positive for tuberculosis (TB) in 57%, bladder biopsies in 54%. For renal TB, intravenous urogram (IVU) and ultrasound were suggestive in about 50% of cases. Ultrasound was very helpful in the diagnosis of testicular TB. Patients underwent surgery in 36% of cases. In contrast to the general trend reported worldwide, surgery was mainly ablative rather than re-constructive. Patient compliance in clinical follow-up and drug therapy was poor. CONCLUSION Surgery for GUTB in Pakistan is still mainly ablative, probably due to a high number of complicated and progressed cases. To date, therapy of GUTB is mainly based on anti-tuberculosis chemotherapy (ATT). However, huge efforts will be required to improve patient compliance without which every therapeutic approach will remain futile.
P-Glycoprotein-Mediated Efflux and Drug Sequestration in Lysosomes Confer Advantages of K562 Multidrug Resistance Sublines to Survive Prolonged Exposure to Cytotoxic Agents

Problem statement: Cellular drug resistance to anticancer agents is major obstacle in cancer chemotherapy and the mechanisms by which these MDR cells possess for protecting themselves to survive prolonged exposure to cytotoxic agents still debating. The study aimed to clarify the role of P-glycoprotein (Pgp) and enhanced drug sequestration in lysosomes to confer the multidrug resistance K562 cells with varied degree of Pgp expression. Approach: Erythromyelogenous leukemic K562 and its corresponding Pgp-over expression K562/adr (RF= 26.5) and K562/10000 (RF = 39.6) cells were used. The transport of intrinsic fluorescence molecules including acridine orange and pirarubicin across plasma membrane of living cells was performed by using spectrofluorometric and flow cytometric analysis. Results: Pirarubicin passively diffused through the plasma membrane of K562, K562/adr and K562/10000 cells with the same values of k+ = 3.4±0.3 pL. s-1.cell-1. Similar results were found for acridine orange, which passively diffused through plasma membrane of these cell lines about 30-fold faster than pirarubicin. The mean rate of Pgp-mediated efflux coefficient (ka) of pirarubicin was equal to 2.6 ± 0.9 pL.s-1.cell-1 for K562/adr and 4.7 ± 1.0 pL.s-1.cell-1 for K562/10000 cells. The Pgp-mediated efflux of acridine orange could not be determined for K562/adr cells while an enhancement of exocytosis in K562/10000 cells was characterized. The acridine orange exhibited antiproliferative activity and IC50 for K562, K562/adr and K562/10000 cells was 447±40, 715±19 and 1,719±258 nM, respectively. Cytotoxicity of acridine orange was increased by 2-fold in the presence of and 25 nM monensin. Conclusion: The results clearly demonstrated for the first time that by using the same methods and cell lines. The predominant cellular defense mechanism determined in multidrug resistant cells depends upon the nature of molecular probes used. As molecular probe, pirarubicin clearly showed that the Pgp-mediated efflux of drug play as predominant mechanism while AO clearly demonstrated the role of drug sequestration in lysosomes following an enhance exocytosis in both MDR sublines.
Indoor allergen levels and other environmental risk factors for sensitization in Estonian homes

The prevalence of allergic disease is low in Eastern Europe for reasons that are poorly understood. Our study aimed to investigate the levels of exposure to indoor allergens and living conditions among Estonian infants in relation to sensitization. Dust samples were collected during four winter months in 1993/94 from the homes of 197 infants participating in a prospective study of sensitization. Information about living conditions was collected through home visit and interviewing the mothers when the children were 6 weeks old. Three dust samples were collected from each home: i.e., from the infant's mattress, bedroom floor, and living‐room carpet. The levels of allergens were determined by ELISA with monoclonal antibodies. The highest allergen level in a home was regarded as the peak value. The peak geometric mean values (±SD) of Der p 1 and Der f 1 were 0.3 (0.07–1.4) μg/g dust, of Can 1, 0.86 (0.23–3.12) μg/g dust, and of Fel d 1, 0.1 (0.01–0.9) μg/g dust. In 12 homes (9%), the peak value of house‐dust mite (HDM) allergens exceeded 2 μg/g dust, with Der p 1 as the dominating allergen. Multivariate analyses indicated that high levels of HDM allergens were more common in apartments that were on the ground floor or first floor, that were heated with stoves, and/or that had a dampness problem. The mean allergen levels at home were similar in children sensitized to HDM (n = 17. 0.29 v.s 0.3 μg/g dust), dog (n=5, 0.55 vs 1.06 μg/g dust, and cat (n= 18, 0.21 vs 0.09 μg/g dust) and in children who were not sensitized to these allergens. Most of the sensitized children were exposed to relatively low allergen levels at home; i.e., below 1 μg/g dust. This level was exceeded in the homes of 4/17 mite‐, 5/18 cat‐, and 0/5 dog‐sensitized children. The similar levels of the major indoor allergens in Estonia and in Scandinavia indicate that the large differences in atopy prevalence among children and young adults in the two regions are not due to differences in allergen exposure. No allergen threshold level for sensitization was identified.
Regulation of differentiation of the BC3H1 muscle cell line through cAMP-dependent and -independent pathways.

Serum mitogens, fibroblast growth factor (FGF), and type beta transforming growth factor (TGF-beta) suppress differentiation of the mouse muscle cell line BC3H1; however, the signal transduction pathways whereby these growth factors exert their effects on this system are unknown. The goal of this study was to determine whether the program for differentiation of BC3H1 cells was susceptible to negative regulation by signaling pathways involving cAMP or protein kinase C and whether these intracellular effectors participate in the mechanism by which growth factors prevent establishment of the myogenic phenotype. Exposure of BC3H1 cells to dibutyryl cAMP, 8-bromo-cAMP, or compounds that stimulate adenylate cyclase, i.e. forskolin, prostaglandin E1, and cholera toxin, prevented up-regulation of muscle-specific gene products following growth arrest in mitogen-deficient medium. Conversely, addition of cAMP to differentiated BC3H1 myocytes caused down-regulation of muscle-specific mRNAs. In contrast to the ability of cAMP to block differentiation, chronic exposure to O-tetradecanoylphorbol-13-acetate, the potent activator of protein kinase C, exhibited no apparent effects on expression of muscle-specific gene products. The proto-oncogenes c-myc and c-fos were up-regulated rapidly by cAMP in a manner similar to that observed previously by serum, FGF, and TGF-beta. However, these growth factors failed to increase intracellular cAMP levels, and they did not induce ornithine decarboxylase, which was subject to positive regulation by cAMP and O-tetradecanoyl-13-acetate. Together, these data indicate that differentiation of BC3H1 cells is subject to negative regulation through a cAMP-dependent pathway and that serum mitogens, FGF, and TGF-beta inhibit differentiation through a mechanism independent of cAMP or protein kinase C.
Ex vivo pretreatment of bone marrow mononuclear cells with endothelial NO synthase enhancer AVE9488 enhances their functional activity for cell therapy

Bone marrow mononuclear cells (BMC) from patients with ischemic cardiomyopathy (ICMP) show a reduced neovascularization capacity in vivo. NO plays an important role in neovascularization, and NO bioavailability is typically reduced in patients with ICMP. We investigated whether the impaired neovascularization capacity of ICMP patient-derived progenitor cells can be restored by pretreatment with the novel endothelial NO synthase (eNOS) transcription enhancer AVE9488 (AVE). Ex vivo pretreatment of BMC from patients with ICMP with AVE significantly increased eNOS mRNA expression by 2.1-fold (P < 0.05) and eNOS activity as assessed by ESR by >3-fold (P < 0.05). The increased eNOS expression was associated with an enhanced migratory capacity in vitro (P < 0.01) and improved neovascularization capacity of the infused BMC in an ischemic hind limb model in vivo (P < 0.001). The improvement in ischemic limb perfusion after infusion of AVE-pretreated BMC resulted in an increase in swimming time (P < 0.05). The enhancement of limb perfusion by AVE-treated BMC was abrogated by ex vivo pretreatment with the eNOS inhibitor NG-nitro-l-arginine methyl ester. Consistently, AVE showed no effect on the impaired migratory capacity of BMC derived from eNOS-deficient mice, documenting the specific involvement of NO. The reduced neovascularization capacity of BMC from patients with ICMP may limit their therapeutic potential in cell therapy studies. Here, we show that pharmacological enhancement of eNOS expression with AVE at least partially reverses the impaired functional activity of BMC from ICMP patients, highlighting the critical role of NO for progenitor cell function.
Antiviral effects of a synthetic Aluminium-Magnesium Silicate, on Avian Influenza Virus

Effects a synthetic Aluminium-Magnesium Silicate [AMS] has on Avian Influenza Virus (AIV) were tested. Equal amounts of AIV samples and of the AMS were mixed, kept one hour at room temperature before centrifuging. The supernatants were remeasured and tested for, viral titre, Mean Death Time (MDT) and Mortality Rate of chicken Embryos (EMR). Volumes of the viral samples reduced at rate of 23.4% ± 5.48%. Viral titres reduced significantly (P < 0.01) from HA, 73 ± 32.72 to 1.4 ± 0.43. Also, EMR of infected chicken embryos reduced from 100% to 65%, while MDT of those that died,increased significantly (P < 0.01) from 76 ± 4.38 to 136 ±18.93 hours. When incubation with AMS was repeated on portions of an AIV sample, MDT increased from 64 to 104 hours with the portion incubated once. AIV portions on which incubation with AMS was repeated could not kill chicken embryos.
Independent differentiative pathways of Ly1 and Ly23 subclasses of T cells. Experimental production of mice deprived of selected T-cell subclasses

When B mice are supplied with Ly1 or Ly23 cells they acquire, over the next 6 mo, only the immune functions associated with each of these T- cell subclasses, respectively. The T-cell population of these "B-Ly1" and "B-Ly23" mice mice also remains restricted to the Ly1 and Ly23 subclass phenotypes. Thus the Ly1 and Ly23 populations are derived from two separate lines of differentiation and are not sequential stages of a single differentiative pathway.
Retrospective comparison of early- versus late-insulin therapy regarding effect on time to resolution of diabetic ketosis and ketoacidosis in dogs and cats: 60 cases (2003-2013).

OBJECTIVE To determine whether early insulin administration (≤6 h after admission) results in more rapid resolution of diabetic ketosis (DK) and ketoacidosis (DKA), shorter duration of hospitalization, and higher incidence of complications, and whether more severe ketonuria is associated with longer time to resolution of DK/DKA. DESIGN Retrospective study (January 1, 2003-March 1, 2013). SETTING University teaching hospital. ANIMALS Sixty dogs and cats with DK or DKA receiving short-acting insulin therapy. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Medical records were reviewed and data recorded including signalment; previous history of diabetes; intake temperature, blood pressure, blood glucose, pH, base excess, and degree of ketonuria; time to short-acting insulin therapy and resolution of DK/DKA; length of hospitalization; and complications. Insulin was initiated ≤6 hours in the early group and >6 hours in the late group after hospital admission. Early group patients had more rapid resolution of DK/DKA after starting short-acting insulin therapy (36.4 ± 22.6 vs. 55.4 ± 26.6 h, P = 0.014). There was no difference in duration of hospitalization or complications. More severe ketonuria resulted in longer time to resolution of DK/DKA after initiation of short-acting insulin (severe: 50.9 ± 24.2; moderate: 29.6 ± 19; mild: 23.4 ± 21.9 h, P = 0.005, all individual pairwise comparisons P < 0.05). CONCLUSIONS Early insulin administration is associated with more rapid resolution of DK/DKA without an associated increase in complication rates. DK/DKA took longer to resolve with more severe ketonuria. Prospective studies are warranted to identify specific time targets for insulin administration in DK/DKA patients.
SlyA and H-NS Regulate Transcription of the Escherichia coli K5 Capsule Gene Cluster, and Expression of slyA in Escherichia coli Is Temperature-dependent, Positively Autoregulated, and Independent of H-NS*

In this paper, we present the first evidence of a role for the transcriptional regulator SlyA in the regulation of transcription of the Escherichia coli K5 capsule gene cluster and demonstrate, using a combination of reporter gene fusions, DNase I footprinting, and electrophoretic mobility shift assays, the dependence of transcription on the functional interplay between H-NS and SlyA. Both SlyA and H-NS bind to multiple overlapping sites within the promoter in vitro, but their binding is not mutually exclusive, resulting in a remodeled nucleoprotein complex. In addition, we show that expression of the E. coli slyA gene is temperature-regulated, positively autoregulated, and independent of H-NS.
Does Exchange Rate Variability Matter for Welfare ?

This paper evaluates quantitatively the potential welfare gains from monetary policy and fixed exchange rate rules in a two-country sticky-price model. The first finding is that the gains from stabilization tend to be small in the types of economic environments emphasized in recent theoretical literature. The analysis goes on to identify two types of economies in which the welfare implications of risk are larger: where agents exhibit habits, and where international asset markets exhibit asymmetry in the form of “original sin. ” In the habits case, monetary policy aimed solely at inflation stabilization is optimal. But in the original sin case there are potentially large welfare gains from also eliminating exchange rate volatility.
Abdominal pain in geriatric emergency patients: variables associated with adverse outcomes.

OBJECTIVE To determine the diagnoses and outcomes of geriatric patients with abdominal pain, and to identify variables associated with adverse outcomes. METHODS Geriatric emergency patients (aged 65 years and older) with a complaint of abdominal pain were participants in this longitudinal case series. Eligible patients were followed by telephone contact and chart review, to determine outcomes and final diagnoses. RESULTS Of 380 eligible patients, follow-up information was available for 375 (97%), for the two months following the ED visit. Final diagnoses included infection (19.2%), mechanical-obstructive disorders (15.7%), ulcers/hypersecretory states (7.7%), urinary tract disease (7.7%), malignancy (7.2%), and others. Although 5.3% of the patients died (related to presenting condition), most (61.3%) patients ultimately recovered. Surgical intervention was required for 22.1% of the patients. Variables associated with adverse outcomes (death, and need for surgical intervention) included hypotension, abnormalities on abdominal radiography, leukocytosis, abnormal bowel sounds, and advanced age. Most physical examination findings were not helpful in identifying patients with adverse outcomes. This study demonstrated a higher incidence of malignancy (7.2%) and a lower incidence of disease necessitating surgical intervention (22.1%) than previously reported. CONCLUSIONS The majority of geriatric emergency patients with abdominal pain have significant disease necessitating hospital admission. Morbidity and mortality among these patients are high, and specific variables are strongly associated with death and the need for surgical intervention. Absence of these variables does not preclude significant disease. Physical examination findings cannot reliably predict or exclude significant disease. These patients should be strongly considered for hospital admission, particularly when fever, hypotension, leukocytosis, or abnormal bowel sounds are present.
ORGAN CULTURE OF ADULT HUMAN SKIN

Proliferation and differentiation of the epidermis in organ culture of adult human skin by the sponge matrix method were studied histologically and autoradiographically, and the following results were obtained: 1) On the first day of culture, mitotic figures were already observable in the epidermis. The outgrowth of epidermal cells at the margins of the explants started. On the second day, there was transformation to a zone that will be referred to as the newly formed stratum corneum in the upper epidermis. 2) On the third and fourth days, the increased growth of epidermal cells caused thickening of the epidermis. Simultaneously, Malpighian cells progressively differentiated into a cornified layer. 3) On and after the fifth day, the basospinous cell layer was reduced in thickness in most of explants. On the ninth and tenth days, DNA synthesis in the basal layer was still obvious, although the epidermis showed a thickness of only one or two cells overlaid with a large number of horny layers. 4) In the culture medium supplemented with corticosteroid, the epidermal growth was slightly depressed with lessened formation of stratum corneum in the early stages of culture as compared with the explants cultured in the basic medium. The reduction of the basospinous layer was scarcely notable after the fifth day. Even after 10–11 days, epidermal cells were well preserved and their stratified squamous architecture was less disorganized. It seemed that corticosteroid could prolong the survival of adult human skin in vitro.