Miracle-dz/UniFAR-FTUs huggingface dataset:
Kaposi's Sarcoma-Associated Herpesvirus MicroRNAs Target GADD45B To Protect Infected Cells from Cell Cycle Arrest and Apoptosis

ABSTRACT Kaposi's sarcoma is one of the most common malignancies in HIV-infected individuals. The responsible agent, Kaposi's sarcoma-associated herpesvirus (KSHV; HHV8), expresses multiple microRNAs (miRNAs), but the targets and functions of these miRNAs are not completely understood. After infection in primary endothelial cells with KSHV, growth arrest DNA damage-inducible gene 45 beta (GADD45B) is one of the most repressed genes using genomic expression profiling. GADD45B was also repressed in mRNA expression profiling experiments when KSHV miRNAs were introduced to uninfected cells. We hypothesized that KSHV miRNAs target human GADD45B to protect cells from consequences of DNA damage, which can be triggered by viral infection. Expression of GADD45B protein is induced by the p53 activator, Nutlin-3, and KSHV miRNA-K9 inhibits this induction. In addition, Nutlin-3 increased apoptosis and cell cycle arrest based on flow cytometry assays. KSHV miR-K9 protected primary endothelial cells from apoptosis and cell cycle arrest following Nutlin-3 treatment. Similar protective phenotypes were seen for targeting GADD45B with short interfering RNAs (siRNAs), as with miR-K9. KSHV miR-K9 also decreased the protein levels of cleaved caspase-3, cleaved caspase-7, and cleaved poly(ADP-ribose) polymerase (PARP). In B lymphocytes latently infected with KSHV, specific inhibitors of KSHV miR-K9 led to increased GADD45B expression and apoptosis, indicating that miR-K9 is important for reducing apoptosis in infected cells. Furthermore, ectopic expression of GADD45B in KSHV-infected cells promoted apoptosis. Together, these results identify a new miRNA target and demonstrate that KSHV miRNAs are important for protecting infected cells from DNA damage responses. IMPORTANCE Kaposi's sarcoma-associated herpesvirus is a leading cause of cancers in individuals with AIDS. Promoting survival of infected cells is essential for maintaining viral infections. A virus needs to combat various cellular defense mechanisms designed to eradicate the viral infection. One such response can include DNA damage response factors, which can promote an arrest in cell growth and trigger cell death. We used a new approach to search for human genes repressed by small nucleic acids (microRNAs) expressed by a gammaherpesvirus (KSHV), which identified a gene called GADD45B as a target of microRNAs. Repression of GADD45B, which is expressed in response to DNA damage, benefited survival of infected cells in response to a DNA damage response. This information could be used to design new treatments for herpesvirus infections.
Mutational analysis and genotype/phenotype correlation in Turkish Charcot–Marie–Tooth Type 1 and HNPP patients

The major Charcot–Marie–Tooth Type 1 (CMT1) locus, CMT1A, and Hereditary neuropathy with liability to pressure palsies (HNPP) cosegregate with a 1.5‐Mb duplication and a 1.5‐Mb deletion, respectively, in band 17p11.2. Point mutations in peripheral myelin gene 22 (PMP22), myelin protein zero (MPZ), and connexin 32 (Cx32) have been reported in CMT1, and in PMP22 in HNPP patients without deletion. We have screened 54 CMT1 patients, of variable clinical severity, and 25 HNPP patients from Turkey, with no duplication or deletion, for mutations in the PMP22 and Cx32 genes. A novel frameshift mutation affecting the second extracellular domain of PMP22 was found in an HNPP patient, while a point mutation in the second transmembrane domain of the protein was detected in a CMT1 patient. Two point mutations affecting different domains of Cx32 were identified in two CMTX patients. Another patient was found to carry a polymorphism in a non‐conserved codon of the Cx32 gene. The clinical phenotypes of the patients correlate well with the effect of the mutation on the protein.
Variation in costs of cone beam CT examinations among healthcare systems.

OBJECTIVES To analyse the costs of cone beam CT (CBCT) in different healthcare systems for patients with different clinical conditions. METHODS Costs were calculated for CBCT performed in Cluj (Romania), Leuven (Belgium), Malmö (Sweden) and Vilnius (Lithuania) on patients with (i) a maxillary canine with eruption disturbance, (ii) an area with tooth loss prior to implant treatment or (iii) a lower wisdom tooth planned for removal. The costs were calculated using an approach based on the identification, measurement and valuation of all resources used in the delivery of the service that combined direct costs (capital equipment, accommodation, labour) with indirect costs (patients' and accompanying persons' time, "out of pocket" costs for examination fee and visits). RESULTS The estimates for direct and indirect costs varied among the healthcare systems, being highest in Malmö and lowest in Leuven. Variation in direct costs was mainly owing to different capital costs for the CBCT equipment arising from differences in purchase prices (range €148 000-227 000). Variation in indirect costs were mainly owing to examination fees (range €0-102.02). CONCLUSIONS Cost analysis provides an important input for economic evaluations of diagnostic methods in different healthcare systems and for planning of service delivery. Additionally, it enables decision-makers to separate variations in costs between systems into those due to external influences and those due to policy decisions. A cost evaluation of a dental radiographic method cannot be generalized from one healthcare system to another, but must take into account these specific circumstances.
A Comparison of Manual Guidance and Knowledge of Results in the Learning of a Weight-bearing Skill

Background and Purpose: Patients with certain neurological or orthopedic conditions often present with asymmetrical weight-bearing in stance. In the treatment of such patients, physical therapists often use manual guidance to promote symmetrical weight-bearing. Research investigating the efficacy of manual guidance to effect a change in weight-bearing status however, is lacking. As a first step in assessing the utility of such guidance, the present study compared the effect of providing two frequencies of manual guidance and of knowledge of results (KR) in the learning of a weight-bearing skill in healthy subjects. Subjects and Methods: Forty healthy subjects (20 males and 20 females) with a mean age of 21.8 years (SD = 4.9 years) were randomly assigned to one of four groups differentiated on the basis of the type and frequency of information provided for learning. Subjects were required to learn to distribute their weight on their feet at a 70:30 ratio. Following a pretest, one group of subjects was positioned by experimenter-provided manual guidance at the hips until 70% of their weight was on one foot, as determined by a bathroom scale. This guidance was provided on every trial for 10 blocks of 12 trials (GD100%). A second group was provided with guidance on every third trial (GD33%), with the other two trials being performed without any assistance. A third group was verbally provided with KR regarding the percentage of body weight on the test foot after every trial (KR100%) while the final group was given KR after every third trial (KR33%). Following acquisition, retention tests were performed 10 minutes, one day, and one week later during which no feedback or guidance was given. Results: No difference between groups was found at the pretest, but an analysis of variance performed on the accuracy of achieving the 70% goal in retention revealed main effects for technique and frequency. These effects were overshadowed by a significant interaction of these variables with retention test. Analysis of this interaction revealed that the most accurate performance was exhibited by the KR33% group while the GD100% group consistently exhibited the poorest learning. The GD33% and KR100% groups showed a decrease in performance accuracy with time following practice. Discussion and Conclusion: These results indicate that infrequent KR was the most effective technique in learning to modify weight-bearing status and that frequent manual guidance during practice is ineffective for learning this task. The next step is to determine whether these findings hold in subjects with various orthopedic and neurological conditions.
Serum-thyroxine levels in microwave-exposed rats.

The nature of the response of the thyroid gland in animals exposed to microwave irradiation is controversial. An enlarged thyroid and an increase of radioiodine uptake in microwave workers have been reported. Absence of thyroid disorders has also been reported in other exposed populations. Animal experimentation has contributed to the controversy because both increased and decreased thyroid functions have been reported. The thyroxine concentration in rats as representative of thyroid function in animals exposed to 2.45-GHz, 120-Hz amplitude-modulated microwaves has been studied. Comparison was made between thyroxine concentrations in microwave- and sham-exposed rats by Student's t test. After a 1-hr exposure, an increased thyroxine concentration was found in rats exposed at 40 and 70 mW/cm2, but not at 1, 5, 10, 20, 50, or 60 mW/cm2. After a 2-hr exposure, increased thyroxine concentration was noted in rats exposed at 25, 30, and 40 mW/cm2, but not at 1, 5, 10, and 20 mW/cm2. After a 4-hr exposure, thyroxine concentration increased in rats exposed at 1 mW/cm2 and decreased in rats exposed at 20 mW/cm2; but changes were not noted at 5 or 10 mW/cm2. Other experiments included animals that were exposed once for 4 hr (0.1, 1, 10, 25, and 40 mW/cm2), sampled 24 hr after a 4-hr exposure (0.1, 1, 10, 25, and 40 mW/cm2), or exposed for 4 hr 3 times (1, 10, 20, 30, 40, and 55 mW/cm2) and 10 times (1, 10, 20, 25, 30, and 40 mW/cm2), to evaluate the consistency of the thyroxine response. None of the rats in these experiments displayed any alteration of thyroxine concentration, except that decreased thyroxine was noted in rats exposed at 40 mW/cm2 for the third time. These studies covered a long time span; rats from two commercial sources (BS and CR) were used and subjected to different numbers of exposures, and therefore these data were evaluated for their stability. Two factors could influence the result significantly, i.e., source of animal and number of sham exposures. Rats used in the 2-hr exposures were from two different commercial sources; rats from CR had a higher (but normal) thyroxine concentration than did rats from BS. Therefore the data of these animals were separated by commercial source for reevaluation. Instead of increased thyroxine concentration in rats exposed at 25, 30, and 40 mW/cm2, changes were not noted in any microwave-exposed rats. The influence of sham exposure revealed that appropriate concurrent control and specification of animal source are needed in longitudinal studies. (ABSTRACT TRUNCATED AT 400 WORDS)
Individual-and Setting-Level Correlates of Secondary Traumatic Stress in Rape Crisis Center Staff

Secondary traumatic stress (STS) is an issue of significant concern among providers who work with survivors of sexual assault. Although STS has been studied in relation to individual-level characteristics of a variety of types of trauma responders, less research has focused specifically on rape crisis centers as environments that might convey risk or protection from STS, and no research to knowledge has modeled setting-level variation in correlates of STS. The current study uses a sample of 164 staff members representing 40 rape crisis centers across a single Midwestern state to investigate the staff member-and agency-level correlates of STS. Results suggest that correlates exist at both levels of analysis. Younger age and greater severity of sexual assault history were statistically significant individual-level predictors of increased STS. Greater frequency of supervision was more strongly related to secondary stress for non-advocates than for advocates. At the setting level, lower levels of supervision and higher client loads agency-wide accounted for unique variance in staff members’ STS. These findings suggest that characteristics of both providers and their settings are important to consider when understanding their STS.
Role of the Frontal Lobes on an Attention Task: A Signal Detection Analysis

Sensitivity and criterion were studied on an attention task requiring detection of new stimuli for a group of 20 patients with unilateral hemispheric damage restricted to the anterior or posterior areas. Patients performed a simple attention task, in which the presence of a novel stimulus had to be detected against the repetition of the same stimulus repeated. Only the site of the lesion (anterior vs posterior damage) influenced the performance of the task. In fact, frontal patients had both lower capacity to discriminate between signals and nonsignals and lower confidence in their responses.
Pair Programming as a Modern Method of Teaching Computer Science

At the Faculty of Education, University of Ljubljana we educate future computer science teachers. Beside didactical, pedagogical, mathematical and other interdisciplinary knowledge, students gain knowledge and skills of programming that are crucial for computer science teachers. For all courses, the main emphasis is the absorption of professional competences, related to the teaching profession and the programming profile. The latter are selected according to the well-known document, the ACM Computing Curricula. The professional knowledge is therefore associated and combined with the teaching knowledge and skills. In the paper we present how to achieve competences related to programming by using different didactical models (semiotic ladder, cognitive objectives taxonomy, problem solving) and modern teaching method â? pair programming
IMPLICATIONS OFGLYCOLYTIC AND PENTOSE PHOSPHATE PATHWAYS 1 ON THE OXIDATIVE STATUS AND MITOCHONDRIAL ACTIVITY OF THE 2 PORCINE OOCYTE DURING IN VITRO MATURATION

22 23 The gGlycolysis and the pentose phosphate pathway (PPP) were modulated in porcine 24 cumulus-oocyte complexes (COCs) during in vitro maturation (IVM) by the addition of 25 inhibitors and stimulators of key enzymes of the pathways, with the aim of to analizing 26 analyze their participation influence on the oxidative status, mitochondrial activity and 27 maturation of the oocyte. The influence of Glycolysis and PPP in COCs were evaluated by 28 lactate production-glucose uptake and by the Brilliant Cresyl Blue test, respectively. 29 Oocyte oxidative and mitochondrial activities were evaluated by Redox Sensor Red CC-1 30 and Mito Tracker Green FM, respectively. pharmacological and physiological inhibitors of 31 glycolysis (NaF and ATP) and PPP (6-AN and NADPH) we validating by assessing 32 glucose and lactate turnover and brilliant cresyl blue staining in oocytes. Modulators of 33 glycolysis and PPP activity significantly perturbed nuclear maturation, oxidative 34 metabolism (Redox Sensor Red CC-1) and mitochondrial mass (Mitotracker Green FM) 35 within oocytes (P < 0.05). In comparison,Oocyte nuclear maturation rate and oxidative and 36 mitochondrial activities decreased in the presence of the pharmacological (NaF) or the 37 physiological (ATP) inhibitors of glycolysis (P<0.05). The pharmacological (6-AN) and the 38 physiological (NADPH) inhibitors of PPP induced a decrease in the oocyte nuclear 39 maturation rate and oxidative and mitochondrial activities (P<0.05). The physiological 40 stimulators of glycolysis (AMP) and PPP (NADP) caused nodid not effect on any of 41 evaluated parameter. In the absence of modulators, We found fluctuations in the oocyte 42 oxidative activity and mitochondrial activities mass were observed during porcine IVM. 43 Comment [MM1]: Mitotracker Green measures mitochondria mass (number), independent of membrane potential (MMP), so it actually doesn’t indicate activity. Rosamine based mitotracker dyes (i.e. Mitotracker Red CMX Ros) do measure MMP. Comment [MM2]: Is this right?
Comparing Perceptions of Cancer Fatalism among African American Patients and Their Providers

Purpose To describe perceptions of cancer fatalism and identify demographic correlates; to explore whether providers believe their patients are fatalistic about cancer and compare these views to the patients’ views. Data sources Both patients (n= 52) and providers (n= 35) were recruited at federally funded, community primary care centers. Data were collected using the Powe Fatalism Inventory, the Perceived Patient Fatalism Inventory, and a demographic data questionnaire. Data were analyzed using descriptive statistics, Pearson correlations, and t‐test. Conclusions The majority of patients were African American women. The majority of providers were physicians and nurses. Patients indicated low perceptions of cancer fatalism, but providers believed patients were highly fatalistic. As the patients’ educational level increased, perceptions of cancer fatalism decreased. Implications for practice The providers’ belief that patients are fatalistic about cancer may influence patient–provider communication. They may be less likely to recommend screening, and patients may be less likely to initiate a discussion about cancer. Strategies are needed that target providers and their patients to address actual and/or perceived perceptions and their influence on cancer screening.
The standard oxygen consumption value equivalent to one metabolic equivalent (3.5 ml/min/kg) is not appropriate for elderly people

In epidemiological studies, estimation of total energy expenditure can only be carried out from using metabolic equivalent (MET) units calculated physical activity questionnaires, where 1 MET is generally assumed to be 3.5 ml/min/kg resting oxygen consumption (VO2 resting). Since the basal metabolic rate varies with age, the energy expenditure equivalent to 1 MET is likely to vary with age. The objective of this study was to determine the energy value for 1 MET in elderly Chinese people compared with younger subjects, using a cross-sectional study. The participants were 138 young adults (88 female, 50 male) aged 16–64 years and 70 elderly adults (35 female, 35 male) aged 65–89 years. VO2 resting was determined by indirect calorimetry (Deltatrac; Datex Division Instrumentraium Corp, Helsinki, Finland). The height and weight were measured. The body fat percentage and lean mass was estimated by body mass index, tricep and bicep skinfold thickness and Bio-impedance analysis. Both VO2 resting and VO2 resting/kg body weight were significantly lower in elderly than young subjects in both gender groups (P<0.01). The significant age difference in VO2 resting remained after adjustment for weight, height and lean mass in both the male group (P<0.001) and the female group (P<0.01). In conclusion, age had an independent effect on VO2 resting, independent of the change of body composition. The present study suggested that the assumption of 1 MET=3.5ml/min/kg VO2 resting may over-estimate energy expenditure when apply to elderly people.
Clinical reliability of CAD/CAM cross-arch zirconia bridges on immediately loaded implants placed with computer-assisted/template-guided surgery: a retrospective study with a follow-up between 3 and 5 years.

PURPOSE The purpose of this study is to retrospectively evaluate the implant and prosthetic survival and success rates of zirconia-based, implant-supported, screw-retained, cross-arch restorations up to 5 years after placement. MATERIALS AND METHODS Twenty-two consecutive edentulous patients (11 males and females, each; mean age 68.3 years) received 26 CAD/CAM cross-arch zirconia implant bridges (NobelProcera™ Implant Bridge Zirconia; Nobel Biocare AG, Zurich, Switzerland) supported by 4 to 10 implants each. All patients were followed for at least 3 years (range 36-60 months, mean 42.3 months). Clinical assessments were scheduled every 4 months during hygiene maintenance. Outcomes were implant and prosthetic survival rates, prosthetic success rate, any observed clinical complications, patient satisfaction, and soft tissue parameters. Fisher's exact test was used to assess associations between categorical variables. RESULTS No dropouts occurred. The overall implant and prostheses survival rate up to 5 years was 100%. Three out of 26 restorations (five out of three hundred forty eight dental units) showed an adhesive chip-off fracture of the veneering ceramic, scoring a cumulative prosthetic success rate of 88.5% at the prosthetic level and 98.6% at the unit level. All 22 patients were functionally and aesthetically highly satisfied with their restorations. Successful soft tissue parameters were found around all implants. CONCLUSIONS Industrially manufactured, zirconia-based, implant-supported, screw-retained, cross-arch restorations are a viable alternative to conventionally manufactured porcelain-fused-to-metal restorations for rehabilitating the edentulous patient.
Pathway based identification of rare mutation effect in cancer

Identifying driver mutation is important in understanding disease mechanism and future application of custom tailored therapeutic decision. Functional analysis of mutational impact usually focuses on the gene expression level of the mutated gene. However, complex regulatory network may cause differential gene expression among functional neighbors of the mutated gene. We suggest a new approach for discovering rare mutations that have real impact in the context of pathway; philosophy of our method is iteratively combining rare mutations until no more mutations can be added, under the condition that the combined mutational event can statistically discriminate pathway level mRNA expression between groups with and without mutation events. Our approach is shown to sensitively capture mutations that change pathway level gene expression at breast cancer data.
Gene-wide tagging study of association between ABCB1 polymorphisms and multidrug resistance in epilepsy in Han Chinese.

AIMS It remains controversial whether polymorphisms of the multidrug resistance gene ABCB1 are associated with pharmacoresistance in epilepsy. To further study the potential association, we genotyped a broad set of tagging SNPs, and explored whether any associations were affected by other host factors. We correlated any association with cerebral mRNA expression of ABCB1. MATERIALS & METHODS A total of 12 tagging and candidate SNPs of ABCB1 were genotyped in 464 Chinese epilepsy patients (270 drug responsive, 194 drug resistant). Genotype and allele distributions in drug-responsive and drug-resistant patients were compared. ABCB1 mRNA was quantified by real-time PCR in brain samples resected from 20 patients with drug-resistant epilepsy. Its level was compared between patients with different genotypes of ABCB1 SNPs found to be associated with drug resistance. RESULTS The intronic polymorphism rs3789243 (p = 0.009 for allele analysis) and the coding polymorphism 2677G/T/A (p = 0.02), and haplotypes containing them, were associated with drug resistance. The 2677G/T/A genotypes remained significantly associated with drug resistance after multiple logistic regression and correction for multiple comparisons. The associations with drug resistance were found in males (p = 0.004 for rs3789243 and p = 0.0007 for 2677T/A>G) but not females, and in patients with localization-related (p = 0.006 for rs3789243 and p = 0.01 for 2677T/A>G) but not idiopathic-generalized epilepsy. ABCB1 mRNA levels did not correlate with genotypes. CONCLUSION In Chinese epilepsy patients, the ABCB1 intronic polymorphism rs3789243 and the coding polymorphism 2677, and haplotypes containing them, may be associated with drug resistance, without an effect on mRNA expression. There was preliminary evidence of interactions between these polymorphisms and gender and epilepsy syndrome.