Miracle-dz/UniFAR-FTUs huggingface dataset:
The impact of renin-angiotensin system polymorphisms on physiological and pathophysiological processes in humans

Purpose of reviewThe renin-angiotensin system plays a central role in health and disease but the determinants of renin-angiotensin system activity have not been fully elucidated. Physiologic genomics continues to be an active area of research that emphasizes definition of phenotype and clarification of non-genomic factors that influence the genotype-phenotype correlation. A common variant of the angiotensinogen gene (T235) predicts elevated levels of circulating angiotensinogen, and polymorphisms of this gene have been linked to physiologic responses and to the risk of cardiovascular disease. The angiotensin-converting-enzyme gene insertion/deletion polymorphism, although not considered functional, has been associated with physiologic responses and disease risk in hypertension and diabetes. A polymorphism of the angiotensin type 1 receptor gene, A1166C, has been the focus of several physiologic studies. These authors will focus on mechanistic studies in normal humans and those with diabetes mellitus or hypertension that examine the impact of these polymorphisms on physiologic responses. Recent findingsRecent studies provide divergent results. Many have shown that mediating factors interfere with the genotype-phenotype correlation. Studies in normal individuals and in those with diabetes mellitus have shown that sodium status and glycemia can alter the impact of genotype. In individuals with essential hypertension, the pathway between genotype and physiology can be disrupted by gender and/or race. SummaryDivergent results in many studies may be attributable to various non-genomic and environmental influences on the pathway between gene polymorphism and physiology. Clarification of these factors should allow a better understanding of genotype-phenotype correlation.
Placebo effects in hearing-aid trials are reliable

Abstract Objective: A recent study suggested that placebo effects are a source of bias in non-blinded hearing-aid trials. Given the potential impact of this finding on the interpretation of non-blinded trials and design of future research trials, the objective of the present study was to investigate the reliability of this effect. Design: Using the same procedure as an earlier study, participants were told that they were taking part in a trial of new hearing-aid technology. Participants compared two devices that were acoustically identical, except one was described as “new” and the other as “conventional”. Participants completed a speech-in-noise test, sound quality ratings, and rated overall personal preference for both hearing aids. Study sample: Sixteen adult hearing-aid users. Results: Participants had significantly better mean speech-in-noise performance (70.9% versus 66.8%, Z = 2.30, p = 0.02, effect size Pearson's r = 0.15) and sound quality ratings for the “new” hearing aid (8.1 versus 7.4, Z = − 2.99, p = 0.003, r = 0.28). A significant proportion of participants (75%) expressed an overall preference for the “new” hearing aid (p = 0.001, effect size φc = 0.66). Conclusion: Placebo effects reliably impact on hearing-aid trials. In order to control for placebo effects, double-blind methodology is optimal. However, when double-blinding is not possible other strategies may be appropriate.
Evaluation of guideline-adherent treatment in cluster headache

Background Several treatment guidelines exist for cluster headache. However, it is not yet known how many cluster headache patients are treated according to these guidelines. Methods We enrolled 434 cluster headache patients with confirmed diagnosis referred to two tertiary pain centers. The history of treatment was registered and analyzed according to the treatment guidelines of the European Federation of Neurological Societies. Results Regarding acute attack treatment, 62.1% of the episodic and 71.0% of the chronic cluster headache patients were treated according to the guidelines. The efficacy rate was above 92% in both groups. Regarding prophylactic treatment, 31.3% of the episodic and 50.9% of the chronic cluster headache patients were treated according to the guidelines. The efficacy rate was 92.8% for episodic and 70.9% for chronic cluster headache. Conclusion The rate of guideline-adherent treatment in cluster headache is about 70% for acute treatment and about 35% for prophylactic treatment. The efficacy of this treatment is significantly higher than the efficacy of non-guideline-adherent treatment.
Functional interaction between DP-1 and p53

The cellular transcription factor DRTF1/E2F and the tumor suppressor protein p53 play important roles in controlling early cell cycle events. DRTF1/E2F is believed to coordinate and integrate the transcription of cell cycle-regulating genes, for example, those involved in DNA synthesis, with the activity of regulatory proteins, such as the retinoblastoma tumor suppressor gene product (pRb), which modulate its transcriptional activity. In contrast, p53 is thought to monitor the integrity of chromosomal DNA and when appropriate interfere with cell cycle progression, for example, in response to DNA damage. Generic DRTF1/E2F DNA binding activity and transcriptional activation arise when members of two distinct families of proteins, such as DP-1 and E2F-1, interact as DP/E2F heterodimers. In many cell types, DP-1 is a widespread component of DRTF1/E2F DNA binding activity which when expressed at high levels oncogenically transforms embryonic fibroblasts. Here, we document an association between DP-1 and p53 and demonstrate its presence in mammalian cell extracts. In vitro p53 interacts with an immunochemically distinct form of DP-1 and in vivo can regulate transcription driven by the DP-1/E2F-1 heterodimer. At the biochemical level, p53 competes with E2F-1 for DP-1, with a consequent reduction in DNA binding activity. Mutational analysis defines within DP-1 a C-terminal region required for the interaction with p53 and within p53 an N-terminal region distinct from that required to bind to MDM2. Our results establish DRTF1/E2F as a common cellular target in growth control mediated through the activities of pRb and p53 and suggest an alternative mechanism through which p53 may regulate cellular proliferation.
Three essays on the financial economics of capital projects

This thesis is comprised of three Chapters addressing theoretical and empirical issues concerning the financing of capital projects. In the first Chapter, Financial advisor reputation and the cost of debt: evidence from project finance loans, we formulate a theoretical model of the role and impact of financial advisors on large-scale investment project loans, and estimate it using a detailed dataset of project finance loans (Projectware). We test competing hypotheses on the value to project sponsors of financial advisors, and we examine the effects on loan characteristics of using common vs. individual advisors. We find that sponsors hire financial advisors to increase their debt levels rather on reducing asymmetric information between them and prospective lenders. In the second Chapter, Banks as both Advisor and Arranger: cost of debt evidence from project finance loans, we study the resolution of the problem of financial advisor reliability. This chapter examines, using data on project finance loans (Projectware), whether financial advisor involvement in the lending syndicate helps to solve their reliability problem. Using Projectware data on project finance (PF loans between 2001 and 2015, we test three competing hypotheses. Overall, our findings show that projects involving banks playing the dual role of FA and MLA have higher loan spreads with longer debt maturity than those without such banks playing the dual role. In the third Chapter, Real option valuation in a Gollier/Weitzman world: the effect of long-run discount rate uncertainty, we first derive an Ingersoll-Ross-type real option model under Gollier/Weitzman long-run discount rate uncertainty, and then apply the model to the case of an oil field investment project. We show how long-run real option value and optimal investment timing are affected, and also that the results are consistent with recent evidence on corporate decision-making under incomplete preferences or ambiguity. We find that, compared with DDR, standard models using constant or mean-reverting interest rates undervalue projects and their real options to wait or to abandon.
The Effects of Political Advertising Message and Candidate Gender on Likelihood to Vote for the Sponsoring Candidate

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The role of preoperative adjuvant treatment in the management of esthesioneuroblastoma: the University of Virginia experience.

OBJECTIVE Multidisciplinary management of esthesioneuroblastoma has effected markedly increased survival during the past 20 years. The potential for radical craniofacial surgery for complete en bloc resection, the availability of advanced neuroimaging modalities, and the incorporation of neoadjuvant therapy into treatment strategies for tumor remission have all contributed to this accomplishment. However, a standard protocol for the management of these lesions has not been accepted; preoperative radiation and chemotherapy have been advocated, but neither radiographic nor clinical response has been quantified. METHODS Thirty-four consecutive patients with biopsy-proven esthesioneuroblastoma treated at one institution from 1976 to 1994 were reviewed to determine the effects of preoperative radiation therapy, with or without chemotherapy, on tumor size and long-term survival. RESULTS In a multivariate regression analysis, advanced age was predictive of decreased disease-free survival (P=0.008), whereas advanced Kadish stage was associated with a borderline higher rate of disease-related mortality (P=0.056). Two-thirds of the patients showed a significant reduction in tumor burden with adjuvant therapy. Patients with response to neoadjuvant therapy demonstrated a significantly lower rate of disease-related mortality (P=0.050). In this series, the overall 5- and 10-year survival rates were 81.0 and 54.5%, respectively. CONCLUSION Preoperative neoadjuvant therapy provides a valuable complement to radical craniofacial resection, leading to reduction in tumor burden. Patients experiencing reduction in tumor volume by neoadjuvant therapy demonstrate an improved prognosis.
Characteristics of drug-induced anaphylaxis in children and adolescents.

BACKGROUND Although data on anaphylaxis in the general population exist for different allergens, there is still lack of detailed etiologic data on drug-induced anaphylaxis (DIA), particularly in children. OBJECTIVE To define the etiology of DIA, to determine the accuracy of drug-related anaphylaxis histories, along with the severity and culprit drug associations among individuals <18 years old. METHODS Patients with a history of drug hypersensitivity reaction (DHR) referred to our center between January 2012 and February 2016 were included. After the collection of European Network for Drug Allergy questionnaire results, initial skin tests and/or provocation tests were performed for the offending drug. RESULTS Among 561 children and adolescents referred due to a suspected DHR, 113 (19%) (median age [interquartile range], 9.6 years [5.4-13.8 years]; 55% boys) had anaphylaxis in their history. At the end of diagnostic evaluation of the patients, 84 (74% of the patients with a history of DIA) were actually hypersensitive to the offending drug. Major drugs that resulted in DIA were antibiotics (33%), nonsteroidal anti-inflammatory drugs (25%), and chemotherapeutics (19%). The majority of patients reported grade 2 (moderate) (45%) and grade 3 (severe) (33%) anaphylactic reactions. A history of systemic illness (41.7 versus 7.1%; p = 0.001), concomitant intake of other drugs regularly (36.9 versus 10.3%; p = 0.007), and the use of chemotherapeutics as the culprit drug (19 versus 0%; p = 0.011) were more frequent, whereas the use of antibiotics was less frequent (34.5 versus 75.9%; p < 0.001) among patients with actual DIA compared to drug tolerant patients. CONCLUSION Three-fourths of the children and adolescents referred due to a suspected history of DIA were found to actually be drug hypersensitive. Prediagnosed systemic illness and different types of drugs would have an impact on the risk of DIA; however, atopic disease or a family history of drug hypersensitivity did not have an impact on actual DIA.
Association between dietary antioxidant vitamins intake/blood level and risk of gastric cancer

We aimed to systematically evaluate the association between dietary intake/blood levels of antioxidant vitamins (vitamin C, vitamin E, β‐carotene, and α‐carotene) and gastric cancer risk. Systematic literature searches were conducted until April 2013 in Pubmed and Embase to identify relevant studies. Either a fixed‐ or a random‐effects model was adopted to estimate overall odds ratios (ORs). Dose–response, meta‐regression, subgroup, and publication bias analyses were applied. Forty articles were finally included in the present study. Higher dietary intake of vitamin C, vitamin E, β‐carotene, and α‐carotene was inversely associated with gastric cancer risk (for vitamin C, pooled OR = 0.58, 95% CI 0.51–0.65; for vitamin E, pooled OR = 0.65, 95% CI 0.57–0.74; for β‐carotene, pooled OR = 0.59, 95% CI 0.49–0.70; for α‐carotene, pooled OR = 0.69, 95% CI 0.52–0.93). Subgroup analyses suggested the effects of these antioxidant vitamins were different in gastric cancer subtypes. As indicated by dose–response analysis, a 100 mg/day increment of vitamin C intake conferred an OR of 0.78 (95% CI 0.67–0.90); a 15 mg/day increment of vitamin E intake conferred an OR of 0.79 (95% CI 0.66–0.94); and a 5 mg/day increment in β‐carotene intake conferred an OR of 0.80 (95% CI 0.60–1.04). No significant association was observed between blood vitamin C, α‐tocopherol, γ‐ tocopherol, β‐carotene and α‐carotene levels and gastric cancer risk. In conclusion, dietary intake of vitamin C, vitamin E, β‐carotene and α‐carotene was inversely associated with gastric cancer risk while no such association was observed for blood levels of these antioxidant vitamins, thus the results should be interpreted cautiously.
Schistosoma mansoni: in vitro and in vivo excretion of CAA and CCA by developing schistosomula and adult worms.

In this study we describe the excretion patterns of circulating anodic (CAA) and cathodic antigen (CCA) by freshly transformed and developing Schistosoma mansoni schistosomula and adult worms. In vitro, CAA and CCA were excreted by the parasites immediately after transformation. During the first days of development CAA and CCA levels were similar, but after 1 wk more CCA was excreted. Neither feeding the schistosomula with red blood cells nor addition of colchicine influenced the rates of antigen excretion. Female worms produced more antigen than males. In heavily infected mice CCA was the first antigen detectable from the third week of infection onward. A few days later, CAA showed a steep increase, becoming the predominant antigen during the course of infection. In urine samples, obtained at the time of perfusion (7 wk), CCA was the predominant antigen. In conclusion, although CAA and CCA levels in serum and urine generally correlate well with worm burden (as determined by egg output), the present study and a literature review show that the actual quantities produced by the worms and detected in the host circulation or excreta may depend on many factors, e.g., host and parasite species, clearance rates, or duration and intensity of infection.
Performance Evaluation of Interactive Data Services Under Sharing and Preemptive Scheduling Disciplines

As specified by the third-generation (3G) wireless networks such as the universal mobile telecommunication system (UMTS), interactive data services, such as Web browsing, voice messaging, and file transfer, represent a major service class in operation nowadays. In this paper, we develop an analytical approach to evaluate the performance of interactive data services under sharing and preemptive scheduling. Specifically, we take into account user interactions in data sessions and the heavy-tailed data file size. Both the mean and the standard deviation of data transfer delay are investigated for the two representative scheduling disciplines. Numerical results are given to show the validity of the evaluation approach and the impact of the on-off user behavior under the scheduling disciplines.
Butterfly Abundance and Movements Among Prairie Patches: The Roles of Habitat Quality, Edge, and Forest Matrix Permeability

Abstract The spatial distribution of patchy insect populations is partly caused by behavioral patterns of insect movement that are influenced by habitat quality, isolation, and the permeability of the surrounding matrix. We recorded insect movements, abundance, and edge behaviors in two species of butterflies, the great-spangled fritillary (Speyeria cybele F., Lepidoptera: Nymphalidae) and the pearl crescent (Phyciodes tharos Drury, Lepidoptera: Nymphalidae), inhabiting remnant prairies surrounded by a forest matrix in south-central Ohio. We also determined the number of forest matrix types present and recorded the permeability of the different types to butterfly movement. The great-spangled fritillary exhibited a relatively high number of interpatch movements, a higher abundance at patch edges, and a propensity to cross the prairie-forest edges, and the forest matrix had a high permeability to butterfly movement. The pearl crescent, in contrast, rarely crossed edge boundaries, moved infrequently among patches, and was more abundant within the patch interior and in patches with high host-plant and flower densities. There were three structurally different forest matrix types separating habitat patches, which in previous studies would have been classified as a single deciduous forest matrix. Butterfly movement and edge behaviors mechanistically interact with patch quality, isolation, and the matrix permeability to determine the spatial structure of these populations in fragmented habitats.
Anticoagulation for patients with cancer and central venous catheters.

BACKGROUND Central venous catheter (CVC) placement increases the risk of thrombosis in cancer patients. Thrombosis often necessitates the removal of the CVC, resulting in treatment delays and thrombosis related morbidity and mortality. OBJECTIVES To evaluate the efficacy and safety of anticoagulation in cancer patients with a CVC. SEARCH STRATEGY We searched The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1 2010), MEDLINE (January 1966 to February 2010; accessed via OVID), EMBASE (January 1980 to February 2010; accessed via OVID) and ISI the Web of Science (1975 to February 2010). We handsearched conference proceedings, checked references of included studies and used the "related article" feature within PubMed. SELECTION CRITERIA Randomized controlled trials (RCTs) comparing any dose of unfractionated heparin (UFH), low molecular weight heparin (LMWH), vitamin K antagonists (VKA), or fondaparinux to no intervention or placebo or comparing two different anticoagulants in cancer patients with a CVC. DATA COLLECTION AND ANALYSIS Two authors independently extracted data from each included study and resolved their disagreements by discussion. MAIN RESULTS Of 8187 identified citations, we included 12 RCTs enrolling 3611 patients and assessing either prophylactic dose heparin or low dose VKAs. Prophylactic dose heparin was not associated with a statistically significant effect on death (relative risk (RR) = 0.85; 95% confidence interval (CI): 0.53 to 1.37), symptomatic deep venous thrombosis (DVT) (RR = 0.54; 95% CI: 0.28 to 1.05) asymptomatic DVT (RR = 0.81; 95% CI: 0.64 to 1.02), major bleeding (RR = 0.68; 95% CI: 0.10 to 4.78), thrombocytopenia (RR = 0.85; 95% CI: 0.49 to 1.46), or infection (RR = 0.91; 95% CI: 0.49 to 1.68). Similarly, low dose VKAs were not associated with a statistically significant effect on death (RR = 0.97; 95% CI: 0.82 to 1.15), symptomatic DVT (RR = 0.63; 95% CI: 0.35 to 1.11) or major bleeding (RR = 6.93; 95% CI: 0.86 to 56.08). However, they were associated with a statistically significant reduction in asymptomatic DVT (RR = 0.42; 95% CI: 0.28 to 0.61). Studies comparing heparin to VKA found no effects on any of the outcomes of interest. AUTHORS' CONCLUSIONS We found no statistically significant effect of heparin or VKA on the outcomes of interest. However, the findings did not rule out clinically important benefits and harms. Patients with cancer with CVCs considering anticoagulation should balance the possible benefit of reduced thromboembolic complications with the possible harms and burden of anticoagulants.