LLukas22/scidocs huggingface dataset:
Host Defense against Viral Infection Involves Interferon Mediated Down-Regulation of Sterol Biosynthesis

Little is known about the protective role of inflammatory processes in modulating lipid metabolism in infection. Here we report an intimate link between the innate immune response to infection and regulation of the sterol metabolic network characterized by down-regulation of sterol biosynthesis by an interferon regulatory loop mechanism. In time-series experiments profiling genome-wide lipid-associated gene expression of macrophages, we show a selective and coordinated negative regulation of the complete sterol pathway upon viral infection or cytokine treatment with IFNγ or β but not TNF, IL1β, or IL6. Quantitative analysis at the protein level of selected sterol metabolic enzymes upon infection shows a similar level of suppression. Experimental testing of sterol metabolite levels using lipidomic-based measurements shows a reduction in metabolic output. On the basis of pharmacologic and RNAi inhibition of the sterol pathway we show augmented protection against viral infection, and in combination with metabolite rescue experiments, we identify the requirement of the mevalonate-isoprenoid branch of the sterol metabolic network in the protective response upon statin or IFNβ treatment. Conditioned media experiments from infected cells support an involvement of secreted type 1 interferon(s) to be sufficient for reducing the sterol pathway upon infection. Moreover, we show that infection of primary macrophages containing a genetic knockout of the major type I interferon, IFNβ, leads to only a partial suppression of the sterol pathway, while genetic knockout of the receptor for all type I interferon family members, ifnar1, or associated signaling component, tyk2, completely abolishes the reduction of the sterol biosynthetic activity upon infection. Levels of the proteolytically cleaved nuclear forms of SREBP2, a key transcriptional regulator of sterol biosynthesis, are reduced upon infection and IFNβ treatment at both the protein and de novo transcription level. The reduction in srebf2 gene transcription upon infection and IFN treatment is also found to be strictly dependent on ifnar1. Altogether these results show that type 1 IFN signaling is both necessary and sufficient for reducing the sterol metabolic network activity upon infection, thereby linking the regulation of the sterol pathway with interferon anti-viral defense responses. These findings bring a new link between sterol metabolism and interferon antiviral response and support the idea of using host metabolic modifiers of innate immunity as a potential antiviral strategy.
Nocturnal enuresis in Turkey: prevalence and accompanying factors in different socioeconomic environments.

AIM
To study the prevalence of nocturnal enuresis and the impact of associated familial factors in Turkish children with a different socioeconomic status.


METHODS
A specific questionnaire was distributed to 3,000 parents of primary school children (6-12 years old). Of these children, 1,500 attended primary schools in Umraniye, a suburban region of Istanbul (group 1), and the other 1,500 children visited schools in Suadiye, a well-developed part of Istanbul (group 2). The first part of the survey investigated the familial conditions of the children (financial status, family history of enuresis, and family size). The second part of the questionnaire surveyed the demographic and physical characteristics of the children. The last part was designed to investigate the opinions and beliefs of the parents about nocturnal enuresis and treatment modalities. The prevalence rates of nocturnal enuresis and associated familial factors of these children from two different regions of Istanbul were compared.


RESULTS
Of the 3,000 questionnaires distributed, 2,589 (86.3%) were returned and included in the final analysis. The mean age of group 1 and 2 children was 8.88 +/- 1.4 and 8.9 +/- 1.5 years, respectively (p > 0.05). The gender of the subjects was equally distributed (48.6% males and 51.4% females). Enuresis was present in 334 children (25.5%) of group 1 and in 205 children (16%) of group 2. Enuresis was significantly more common in group 1 (p < 0.01). The families consisted of 4.69 +/- 1.4 and 4.1 +/- 1.1 persons, respectively (p < 0.01). A yearly income of USD 7,000 was achieved in group 2 by 54%, in group 1 by only 0.7% (p < 0.01). Only 26 children of group 1 (7.8%) and 22 children of group 2 (10.8%) were noted to receive medical enuresis treatments, with no statistically significant difference between the groups (p > 0.01). The parents of the enuretic children from the suburban region of Istanbul were found to consider the condition a normal developmental entity. They believed that enuresis will resolve spontaneously and that no treatment is necessary. On the contrary, the parents of the enuretic children in the well-developed region of the city believed that enuresis is a psychological problem and that intensive psychological assistance is essential for the management.


CONCLUSIONS
Our study indicates that the prevalence of nocturnal enuresis in Turkey is comparable to that reported in the literature. The parents consider that enuresis nocturna is not a fatal disorder, that the drugs used in the treatment may be harmful, and that no medical assistance is required. Trained health personnel and physicians should inform the parents about enuresis in order to prevent possible behavioral and self-esteem problems.
Patterns of third-molar agenesis and associated dental anomalies in an orthodontic population.

INTRODUCTION
The aim of this study was to investigate the frequency of dental anomalies in orthodontic patients with different patterns of third-molar agenesis, comparing them with patients without third-molar agenesis.


METHODS
A sample of 374 patients with agenesis of at least 1 third molar was divided into 4 groups according to the third-molar agenesis pattern, and a control group of 98 patients without third-molar agenesis was randomly selected from the patient archives. Panoramic radiographs and cast models were used to determine the associated dental anomalies, such as hypodontia, hyperdontia, impaction, dilaceration, microdontia, ectopic eruption, transposition, and transmigration. The Pearson chi-square and Fisher exact tests were used to determine the differences in the distribution of the associated dental anomalies among the groups.


RESULTS
The prevalence of agenesis of other teeth (11.2%, n = 42) was significantly greater in our study sample (groups 1-4) than in the control group (group 5) (4.1%, n = 4; P <0.05). When we compared the groups according to the various third-molar agenesis patterns, we found that agenesis of other teeth was more common in patients with agenesis of 3 and 4 third molars. In addition, the patients with agenesis of 4 third molars exhibited maxillary lateral-incisor microdontia more frequently. Another important finding was a higher prevalence of total dental anomalies in patients with agenesis of 3 and 4 third molars compared with the control group.


CONCLUSIONS
Permanent tooth agenesis, microdontia of maxillary lateral incisors, and total dental anomalies are more frequently associated with agenesis of 4 third molars than with the presence of third molars.
SCANNING DYNAMIC COMPETITIVE LANDSCAPES : A MARKET-BASED AND RESOURCE-BASED FRAMEWORK

Heterogeneity among rivals implies that each firm faces a unique competitive set, despite overlapping market domains. This suggests the utility of a firm-level approach to competitor identification and analysis, particularly under dynamic environmental conditions. We take such an approach in developing a market-based and resource-based framework for scanning complex competitive fields. By facilitating a search for functional similarities among products and resources, the framework reveals relevant commonalities in an otherwise heterogeneous competitive set. Beyond its practical contribution, the paper also advances resource-based theory as a theory of competitive advantage. Most notably, we show that resource substitution conditions not only the sustainability of a competitive advantage, but the attainment of competitive advantage as well. With equifinality among resources of different types, the rareness condition for even temporary competitive advantage must include resource substitutes. It is not rareness in terms of resource type that matters, but rareness in terms of resource functionality. Copyright  2003 John Wiley & Sons, Ltd.
Pedagogical utilization and assessment of the statistic online computational resource in introductory probability and statistics courses

Technology-based instruction represents a new recent pedagogical paradigm that is rooted in the realization that new generations are much more comfortable with, and excited about, new technologies. The rapid technological advancement over the past decade has fueled an enormous demand for the integration of modern networking, informational and computational tools with classical pedagogical instruments. Consequently, teaching with technology typically involves utilizing a variety of IT and multimedia resources for online learning, course management, electronic course materials, and novel tools of communication, engagement, experimental, critical thinking and assessment.The NSF-funded Statistics Online Computational Resource (SOCR) provides a number of interactive tools for enhancing instruction in various undergraduate and graduate courses in probability and statistics. These resources include online instructional materials, statistical calculators, interactive graphical user interfaces, computational and simulation applets, tools for data analysis and visualization. The tools provided as part of SOCR include conceptual simulations and statistical computing interfaces, which are designed to bridge between the introductory and the more advanced computational and applied probability and statistics courses. In this manuscript, we describe our designs for utilizing SOCR technology in instruction in a recent study. In addition, present the results of the effectiveness of using SOCR tools at two different course intensity levels on three outcome measures: exam scores, student satisfaction and choice of technology to complete assignments. Learning styles assessment was completed at baseline. We have used three very different designs for three different undergraduate classes. Each course included a treatment group, using the SOCR resources, and a control group, using classical instruction techniques. Our findings include marginal effects of the SOCR treatment per individual classes; however, pooling the results across all courses and sections, SOCR effects on the treatment groups were exceptionally robust and significant. Coupling these findings with a clear decrease in the variance of the quantitative examination measures in the treatment groups indicates that employing technology, like SOCR, in a sound pedagogical and scientific manner enhances overall the students' understanding and suggests better long-term knowledge retention.
AN OVERVIEW OF PREPROCESSING OF WEB LOG FILES FOR WEB USAGE MINING

With the Internet usage gaining popularity and the steady growth of users, the World Wide Web has become a huge repository of data and serves as an important platform for the dissemination of information. The users’ accesses to Web sites are stored in Web server logs. However, the data stored in the log files do not present an accurate picture of the users’ accesses to the Web site. Hence, preprocessing of the Web log data is an essential and pre-requisite phase before it can be used for knowledge-discovery or mining tasks. The preprocessed Web data can then be suitable for the discovery and analysis of useful information referred to as Web mining. Web usage mining, a classification of Web mining, is the application of data mining techniques to discover usage patterns from clickstream and associated data stored in one or more Web servers. This paper presents an overview of the various steps involved in the preprocessing stage.
An Optimal Graph Theoretic Approach to Data Clustering: Theory and Its Application to Image Segmentation

(57) Data collected from devices and human condition may be used to forewarn of critical events such as machine/structural failure or events from brain/heart wave data stroke. By moni toring the data, and determining what values are indicative of a failure forewarning, one can provide adequate notice of the impending failure in order to take preventive measures. This disclosure teaches a computer-based method to convert dynamical numeric data representing physical objects (un structured data) into discrete-phase-space states, and hence into a graph (Structured data) for extraction of condition change. ABSTRACT
A Birth-cohort testing intervention identified hepatitis c virus infection among patients with few identified risks: a cross-sectional study

BACKGROUND
International guidelines and U.S. guidelines prior to 2012 only recommended testing for hepatitis C virus (HCV) infection among patients at risk, but adherence to guidelines is poor, and the majority of those infected remain undiagnosed. A strategy to perform one-time testing of all patients born during 1945-1965, birth cohort testing, may diagnose HCV infection among patients whose risk remains unknown. We sought to determine if a birth-cohort testing intervention for HCV antibody positivity helped identify patients with fewer documented risk factors or medical indications than a pre-intervention, risk-based testing strategy.


METHODS
We used a cross-sectional design with retrospective electronic medical record review to examine patients identified with HCV antibody positivity (Ab+) during a pre-intervention (risk-based) phase, the standard of care at the time, vs. a birth-cohort testing intervention phase. We compared demographic and clinical characteristics and HCV risk-associated factors among patients whose HCV Ab + was identified during the pre-intervention (risk-based testing) vs. post birth-cohort intervention phases. Study subjects were patients identified as HCV-Ab + in the baseline (risk-based) and birth-cohort testing phases of the Hepatitis C Assessment and Testing (HepCAT) Project.


RESULTS
Compared to the risk-based phase, patients newly diagnosed with HCV Ab + after the birth-cohort intervention were significantly less likely to have a history of any substance abuse (30.5% vs. 49.5%, p = 0.02), elevated alanine transaminase levels of > 40 U/L (22.0% vs. 46.7%, p = 0.002), or the composite any risk-associated factor (55.9% vs. 79.0%, p = 0.002).


CONCLUSIONS
Birth-cohort testing is an useful strategy for identifying previously undiagnosed HCV Ab + because it does not require providers ask risk-based questions, or patients to disclose risk behaviors, and appears to identify HCV Ab + in patients who would not have been identified using a risk-based testing strategy.
Depression, anxiety and stress in dental students

Objectives
To measure the occurrence and levels of depression, anxiety and stress in undergraduate dental students using the Depression, Anxiety and Stress Scale (DASS-21).


Methods
This cross-sectional study was conducted in November and December of 2014. A total of 289 dental students were invited to participate, and 277 responded, resulting in a response rate of 96%. The final sample included 247 participants. Eligible participants were surveyed via a self-reported questionnaire that included the validated DASS-21 scale as the assessment tool and questions about demographic characteristics and methods for managing stress.


Results
Abnormal levels of depression, anxiety and stress were identified in 55.9%, 66.8% and 54.7% of the study participants, respectively. A multiple linear regression analysis revealed multiple predictors: gender (for anxiety b=-3.589, p=.016 and stress b=-4.099, p=.008), satisfaction with faculty relationships (for depression b=-2.318, p=.007; anxiety b=-2.213, p=.004; and stress b=-2.854, p<.001), satisfaction with peer relationships (for depression b=-3.527, p<.001; anxiety b=-2.213, p=.004; and stress b=-2.854, p<.001), and dentistry as the first choice for field of study (for stress b=-2.648, p=.045). The standardized coefficients demonstrated the relationship and strength of the predictors for each subscale. To cope with stress, students engaged in various activities such as reading, watching television and seeking emotional support from others.


Conclusions
The high occurrence of depression, anxiety and stress among dental students highlights the importance of providing support programs and implementing preventive measures to help students, particularly those who are most susceptible to higher levels of these psychological conditions.
Smoothing spline estimation of variance functions

This article considers spline smoothing of variance functions. We focus on selection of the smoothing parameters and develop three direct data-driven methods: unbiased risk (UBR), generalized approximate cross-validation (GACV), and generalized maximum likelihood (GML). In addition to guaranteed convergence, simulations show that these direct methods perform better than existing indirect UBR, generalized cross-validation (GCV), and GML methods. The direct UBR and GML methods perform better than the GACV method. An application to array-based comparative genomic hybridization data illustrates the usefulness of the proposed methods.
Safety of the Up-titration of Nifedipine GITS and Valsartan or Low-dose Combination in Uncontrolled Hypertension: the FOCUS Study.

PURPOSE
Doubling the dose of antihypertensive drugs is necessary to manage hypertension in patients whose disease is uncontrolled. However, this strategy can result in safety issues. This study compared the safety and efficacy of up-titration of the nifedipine gastrointestinal therapeutic system (GITS) with up-titration of valsartan monotherapy; these were also compared with low-dose combinations of the two therapies.


METHODS
This prospective, open-label, randomized, active-controlled, multicenter study lasted 8 weeks. If patients did not meet the target blood pressure (BP) after 4 weeks of treatment with low-dose monotherapy, they were randomized to up-titration of the nifedipine GITS dose from 30 mg (N30) to 60 mg or valsartan from 80 mg to 160 mg or they were randomized to receive a low-dose combination of N30 and valsartan 80 mg for another 4 weeks. BP variability was assessed by using the SD or the %CV of the short-term BP measured at clinic.


FINDINGS
Of the 391 patients (20~70 years with stage II or higher hypertension) screened for study inclusion, 362 patients who had 3 BP measurements were enrolled. The reduction in the mean systolic/diastolic BP from baseline to week 4 was similar in both low-dose monotherapy groups with either N30 or valsartan 80 mg. BP variability (SD) was unchanged with either therapy, but the %CV was slightly increased in the N30 group. There was no significant difference in BP variability either in SD or %CV between responders and nonresponders to each monotherapy despite the significant difference in the mean BP changes. The up-titration effect of nifedipine GTS from 30 to 60 mg exhibited an additional BP reduction, but this effect was not shown in the up-titration of valsartan from 80 to 160 mg. Although the difference in BP was obvious between high-dose nifedipine GTS and valsartan, the BP variability was unchanged between the 2 drugs and was similar to the low-dose combinations. There was a low rate of adverse events in all treatment groups. In addition, escalating the dose of either nifedipine GITS or valsartan revealed a similar occurrence of adverse effects with low-dose monotherapy or the low-dose combination.


IMPLICATIONS
Compared with up-titration of the angiotensin receptor blocker valsartan, up-titration of the calcium channel blocker nifedipine GITS provided no additional increased safety concerns and revealed better mean reductions in BP without affecting short-term BP variability. ClinicalTrials.gov identifier: NCT01071122.
Prebiopsy Multiparametric Magnetic Resonance Imaging for Prostate Cancer Diagnosis in Biopsy-naive Men with Suspected Prostate Cancer Based on Elevated Prostate-specific Antigen Values: Results from a Randomized Prospective Blinded Controlled Trial.

BACKGROUND
Multiparametric magnetic resonance imaging (MP-MRI) may improve the detection of clinically significant prostate cancer (PCa).


OBJECTIVE
To compare MP-MRI transrectal ultrasound (TRUS)-fusion targeted biopsy with routine TRUS-guided random biopsy for overall and clinically significant PCa detection among patients with suspected PCa based on prostate-specific antigen (PSA) values.


DESIGN, SETTING, AND PARTICIPANTS
This institutional review board-approved, single-center, prospective, randomized controlled trial (April 2011 to December 2014) included 130 biopsy-naive patients referred for prostate biopsy based on PSA values (PSA <20 ng/ml or free-to-total PSA ratio ≤0.15 and PSA <10 ng/ml). Patients were randomized 1:1 to the MP-MRI or control group. Patients in the MP-MRI group underwent prebiopsy MP-MRI followed by 10- to 12-core TRUS-guided random biopsy and cognitive MRI/TRUS fusion targeted biopsy. The control group underwent TRUS-guided random biopsy alone.


INTERVENTION
MP-MRI 3-T phased-array surface coil.


OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
The primary outcome was the number of patients with biopsy-proven PCa in the MP-MRI and control groups. Secondary outcome measures included the number of positive prostate biopsies and the proportion of clinically significant PCa in the MP-MRI and control groups. Between-group analyses were performed.


RESULTS AND LIMITATIONS
Overall, 53 and 60 patients were evaluable in the MP-MRI and control groups, respectively. The overall PCa detection rate and the clinically significant cancer detection rate were similar between the MP-MRI and control groups, respectively (64% [34 of 53] vs 57% [34 of 60]; 7.5% difference [95% confidence interval (CI), -10 to 25], p=0.5, and 55% [29 of 53] vs 45% [27 of 60]; 9.7% difference [95% CI, -8.5 to 27], p=0.8). The PCa detection rate was higher than assumed during the planning of this single-center trial.


CONCLUSIONS
MP-MRI/TRUS-fusion targeted biopsy did not improve PCa detection rate compared with TRUS-guided biopsy alone in patients with suspected PCa based on PSA values.


PATIENT SUMMARY
In this randomized clinical trial, additional prostate magnetic resonance imaging (MRI) before prostate biopsy appeared to offer similar diagnostic accuracy compared with routine transrectal ultrasound-guided random biopsy in the diagnosis of prostate cancer. Similar numbers of cancers were detected with and without MRI.


TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT01357512.