Miracle-dz/UniFAR-FTUs huggingface dataset:
Bortezomib as a Potential Treatment for Prostate Cancer

Androgen ablation and chemotherapy provide effective palliation for most patients with advanced prostate cancer, but eventually progressing androgen-independent prostate cancer threatens the lives of patients usually within a few years, mandating improvement in therapy. Proteasome inhibition has been proposed as a therapy target for the treatment of solid and hematological malignancies. The proteasome is a ubiquitous enzyme complex that is a hub for the regulation of many intracellular regulatory pathways; because of its essential function, this enzyme has become a new target for cancer treatment. Studies with bortezomib (VELCADE, formerly known as PS-341) and other proteasome inhibitors indicate that cancer cells are especially dependent on the proteasome for survival, and several mechanisms used by prostate cancer cells require proteasome function. Bortezomib has been studied extensively in vitro and in vivo, and anticancer activity has been seen in cell and animal models for several solid tumor types, including prostate cancer. A Phase I trial to determine the maximum tolerated dose of once-weekly bortezomib has been completed. This trial included a large fraction of patients with androgen-independent prostate cancer. The maximum tolerated dose was reached at 1.6 mg/m2. A correlation was seen among bortezomib dose, proteasome inhibition, and positive modulation of serum prostate-specific antigen. There was also evidence of down-regulation of serum interleukin 6, a downstream nuclear factor κB effector. This Phase I trial and preclinical studies support additional testing of bortezomib in combination with radiation or chemotherapy for androgen-independent prostate cancer.
Mutual information in rank-one matrix estimation

We consider the estimation of a n-dimensional vector x from the knowledge of noisy and possibility non-linear element-wise measurements of xxT, a very generic problem that contains, e.g. stochastic 2-block model, submatrix localization or the spike perturbation of random matrices. Using an interpolation method proposed by Guerra [1] and later refined by Korada and Macris [2], we prove that the Bethe mutual information (related to the Bethe free energy and conjectured to be exact by Lesieur et al. [3] on the basis of the non-rigorous cavity method) always yields an upper bound to the exact mutual information. A lower bound is also provided using a similar technique. For concreteness, we illustrate our findings on the sparse PCA problem, and observe that (a) our bounds match for a large region of parameters and (b) that there exists a phase transition in a region where the spectrum remains uninformative. While we present only the case of rank-one symmetric matrix estimation, our proof technique is readily extendable to low-rank symmetric matrix or low-rank symmetric tensor estimation.
Task Difficulty Modulates the Impact of Emotional Stimuli on Neural Response in Cognitive-Control Regions

Both heightened reactivity to emotional stimuli and impaired cognitive control are key aspects of depression, anxiety, and addiction. But the impact of emotion on cognitive-control processes, and the factors that modulate this impact, are still not well understood. We examined the effects of threat and reward distracters on the neural correlates of cognitive control using functional MRI (fMRI) and the Multi-Source Interference Task (MSIT). Behaviorally, subjects were slower and less accurate on the more demanding incongruent trials compared to the easier congruent trials. In addition, both threat and reward distracters significantly impaired the speed of responding on incongruent trials relative to the no-distracter condition. At the neural level, we used the incongruent – congruent contrast to functionally define four cognitive-control regions of interest (ROIs): anterior cingulate cortex (ACC), left and right inferior frontal gyrus (IFG)/insula, and right dorsolateral prefrontal cortex (DLPFC). A repeated-measures analysis of variance on the extracted contrast values in these ROIs indicated a significant interaction of stimulus salience and task difficulty on the neural response in cognitive-control regions. Specifically, threat distracters significantly decreased the response in cognitive-control regions on incongruent trials, whereas they significantly increased that response on congruent trials, relative to the no-distracter condition. Exploratory analyses of the amygdala response showed a similar interaction of stimulus salience and task difficulty: threat distracters significantly decreased the amygdala response only on incongruent trials. Overall, our results suggest that the impact of emotional distracters on the neural response in cognitive-control regions as well as in the amygdala is modulated by task difficulty, and add to our understanding of the factors that determine whether emotion enhances or impairs cognition.
Concepts of comorbidities, multiple morbidities, complications, and their clinical epidemiologic analogs

The proportion of older people in the world population is expected to increase rapidly during the upcoming decades. Consequently, the number of patients with multimorbidity will increase dramatically. In epidemiologic research, the concepts of multimorbidity, comorbidity, and complications have been confusing, and some of these concepts are used interchangeably. In this commentary, the authors propose a clear terminology for clinical concepts describing different aspects of multimorbidity and elucidate the relationship between these clinical concepts and their epidemiologic analogs. Depending on whether a study uses causal or predictive models, a proper distinction between concepts of multimorbidity is important. It can be very difficult to separate complications of the index disease under study from comorbidity. In this context, use of comorbidity indices as confounding scores should be done with caution. Other methodologic issues are type, duration, severity, and number of comorbidities included in the ascertainment methods, as well as sources included in the research. Studies that recognize these challenges have the potential to yield valid estimates of the comorbidity burden and results that can be compared with other studies.
QT Dispersion Does Not Represent Electrocardiographic Interlead Heterogeneity of Ventricular Repolarization

QT Dispersion and Repolarization Heterogeneity. Introduction: QT dispersion (QTd, range of QT intervals in 12 ECG leads) is thought to reflect spatial heterogeneity of ventricular refractoriness. However, QTd may be largely due to projections of the repolarization dipole rather than “nondipolar” signals.
Radiographic features and outcome of root canal treatment carried out in the Łódź region of Poland.

AIM The aim of this study was to assess the radiographic features and factors affecting the long-term results of root canal treatment in the Lódź region of Poland. METHODOLOGY Three hundred and fifty-five periapical radiographs of previously endodontically treated teeth (282 root-filled teeth and 73 teeth with pulpotomy) from 236 patients were evaluated in the study. The patients were aged from 15 to 76 years and randomly selected amongst subjects referred to the Institute of Dentistry. Medical University of Lódź and two private dental practices. The radiographs were examined by the authors according to criteria proposed by De Cleen et al. (1993) using an illuminated viewbox in a dark room. The Fisher's exact test was used to compare the frequencies in teeth groups. RESULTS Amongst root-filled teeth, 49% were adequately filled within 0-2 mm of the radiographic apex. Periapical radiolucencies were observed in 25% of root-filled teeth. Teeth without periapical pathosis were more often filled within 0-2 mm of the apex (59%) than teeth with pathosis (17%). Teeth were most often adequately filled (64%) in patients attending the Institute of Dentistry. In patients attending the dental outpatients' departments, 71% of teeth were inadequately filled. Amongst the teeth treated with pulpotomy, 67% had a periapical radiolucency. CONCLUSION The radiographic technical quality of the root canal treatment was associated with the outcome that root fillings of adequate standard were associated with health more often than inadequate root fillings. Pulpotomy was associated with periapical disease in the majority of cases.
Measuring the Quality of Approximate Solutions to Zero-One Programming Problems

Abstract : The difficulties associated with measuring the are defined of an approximate (heuristic) solution by 'Percentage-Error' as is customary are pointed out. A set of properties that are to be expected from a proper measure of solution quality are defined and the family of functions which satisfy those conditions are investigated. In particular, it is shown that for any class of 0-1 programming problems appropriate functions do exist and that they are uniquely defined up to monotone transformations. Several examples of linear functions which are suitable for certain classes of problems are included.
The F-Box Protein Rcy1p Is Involved in Endocytic Membrane Traffic and Recycling Out of an Early Endosome in Saccharomyces cerevisiae

In Saccharomyces cerevisiae, endocytic material is transported through different membrane-bound compartments before it reaches the vacuole. In a screen for mutants that affect membrane trafficking along the endocytic pathway, we have identified a novel mutant disrupted for the gene YJL204c that we have renamed RCY1 (recycling 1). Deletion of RCY1 leads to an early block in the endocytic pathway before the intersection with the vacuolar protein sorting pathway. Mutation of RCY1 leads to the accumulation of an enlarged compartment that contains the t-SNARE Tlg1p and lies close to areas of cell expansion. In addition, endocytic markers such as Ste2p and the fluorescent dyes, Lucifer yellow and FM4-64, were found in a similar enlarged compartment after their internalization. To determine whether rcy1Δ is defective for recycling, we have developed an assay that measures the recycling of previously internalized FM4-64. This method enables us to follow the recycling pathway in yeast in real time. Using this assay, it could be demonstrated that recycling of membranes is rapid in S. cerevisiae and that a major fraction of internalized FM4-64 is secreted back into the medium within a few minutes. The rcy1Δ mutant is strongly defective in recycling.
Abnormal anxiety‐related behavior in serotonin transporter null mutant mice: the influence of genetic background

Serotonin transporter (5‐HTT) null mutant mice provide a model system to study the role genetic variation in the 5‐HTT plays in the regulation of emotion. Anxiety‐like behaviors were assessed in 5‐HTT null mutants with the mutation placed on either a B6 congenic or a 129S6 congenic background. Replicating previous findings, B6 congenic 5‐HTT null mutants exhibited increased anxiety‐like behavior and reduced exploratory locomotion on the light ↔ dark exploration and elevated plus‐maze tests. In contrast, 129S6 congenic 5‐HTT null mutant mice showed no phenotypic abnormalities on either test. 5‐HTT null mutants on the 129S6 background showed reduced 5‐HT1A receptor binding (as measured by quantitative autoradiography) and reduced 5‐HT1A receptor function (as measured by 8‐OH‐DPAT‐indcued hypothermia). These data confirm that the 5‐HTT null mutation produced alterations in brain 5‐HT function in mice on the 129S6 background, thereby discounting the possibility that the absence of an abnormal anxiety‐like phenotype in these mice was due to a suppression of the mutation by 129 modifier genes. Anxiety‐like behaviors in the light ↔ dark exploration and elevated plus‐maze tests were significantly higher in 129S6 congenic +/+ mice as compared to B6 congenic +/+ mice. This suggests that high baseline anxiety‐like behavior in the 129S6 strain might have precluded detection of the anxiety‐like effects of the 5‐HTT null mutation on this background. Present findings provide further evidence linking genetic variation in the 5‐HTT to abnormalities in mood and anxiety. Furthermore, these data highlight the utility of conducting behavioral phenotyping of mutant mice on multiple genetic backgrounds.
An Event-Related Brain Potential Analysis of Visual Word Priming Effects

Two experiments are reported that provide evidence on task-induced effects during visual lexical processing in a prime-target semantic priming paradigm. The research focuses on target expectancy effects by manipulating the proportion of semantically related and unrelated word pairs. In Experiment 1, a lexical decision task was used and reaction times (RTs) and event-related brain potentials (ERPs) were obtained. In Experiment 2, subjects silently read the stimuli, without any additional task demands, and ERPs were recorded. The RT and ERP results of Experiment 1 demonstrate that an expectancy mechanism contributed to the priming effect when a high proportion of related word pairs was presented. The ERP results of Experiment 2 show that in the absence of extraneous task requirements, an expectancy mechanism is not active. However, a standard ERP semantic priming effect was obtained in Experiment 2. The combined results show that priming effects due to relatedness proportion are induced by task demands and are not a standard aspect of online lexical processing.
Regularly random duality

In this paper we look at a class of random optimization problems. We discuss ways that can help determine typical behavior of their solutions. When the dimensions of the optimization problems are large such an information often can be obtained without actually solving the original problems. Moreover, we also discover that fairly often one can actually determine many quantities of interest (such as, for example, the typical optimal values of the objective functions) completely analytically. We present a few general ideas and emphasize that the range of applications is enormous.
Comparison of Home and Clinic-Based HIV Testing Among Household Members of Persons Taking Antiretroviral Therapy in Uganda: Results From a Randomized Trial

Objective:Due to high rates of undiagnosed and untreated HIV infection in Africa, we compared HIV counseling and testing (VCT) uptake among household members of patients receiving antiretroviral therapy. Methods:HIV-infected persons attending an AIDS clinic were randomized to a home-based or clinic-based antiretroviral therapy program including VCT for household members. Clinic arm participants were given free VCT vouchers and encouraged to invite their household members to the clinic for VCT. Home arm participants were visited, and their household members offered VCT using a 3-test rapid finger-stick testing algorithm. VCT uptake and HIV prevalence were compared. Findings:Of 7184 household members, 3974 (55.3%) were female and 4798 (66.8%) were in the home arm. Home arm household members were more likely to receive VCT than those from the clinic arm (55.8% vs. 10.9%, odds ratio: 10.41, 95% confidence interval: 7.89 to 13.73; P < 0.001), although the proportion of HIV-infected household members was higher in the clinic arm (17.3% vs. 7.1%, odds ratio: 2.76, 95% confidence interval: 1.97 to 3.86, P < 0.001). HIV prevalence among all household members tested in the home arm was 56% compared with 27% in the clinic arm. Of 148 spouses of HIV-infected patients, 69 (46.6%) were uninfected. Persons aged 15-24 were less likely to test than other age groups, and in the home arm, women were more likely to test than men. Conclusions:Home-based VCT for household members of HIV-infected persons was feasible, associated with lower prevalence, higher uptake, and increased identification of HIV-infected persons than clinic-based provision.
Self-heating of polymeric laminated composite plates under the resonant vibrations: Theoretical and experimental study

The self-heating effect caused by the energy dissipation during vibration of viscoelastic materials is an important criterion in the evaluation of the structural degradation. In this study the theoretical model of the self-heating of the polymeric layered FRP plate subjected to the resonant vibration was proposed. The model is based on the complex parameters, which could be obtained in DMA tests. The theoretical model is validated in several experiments. The experiment contains two stages: first, the modal analysis was performed for the evaluation of natural frequencies of vibration and further the specimens were excited to harmonic vibration with their resonant frequencies in the constant strain rate mode. During the second stage the force response and evolution of the temperature distributions on the surface of the specimens were registered. Obtained results allow identifying the self-heating temperature evolution of the composite and determining the relation of the excitation frequency and self-heating temperature. Several phenomena observed during the experiments were interpreted following their physical nature. Investigated problem could be applied for predicting the structural life of such composites and in diagnostics and structural health monitoring of the parts and constructions made of polymeric composites. POLYM. COMPOS. , 2012. © 2011 Society of Plastics Engineers
Cost‐effectiveness of pretransplant sofosbuvir for preventing recurrent hepatitis C virus infection after liver transplantation

There are reports of pretransplant sofosbuvir (SOF) plus ribavirin being effective in preventing recurrent hepatitis C virus (HCV) infection after liver transplantation (LT). The aim of this study was to assess the cost‐effectiveness of this strategy in the area served by the North Italy Transplant program. We retrospectively assessed the impact of HCV infection on post‐LT survival in 2376 consecutive adult patients (MELD ≤ 25, unknown genotype, period 2004–2009) and the prevalence costs of conventional standard of care (SOC) antiviral therapy (pegylated interferon plus ribavirin) after LT. A Markov model was developed to compare two strategies: 12–24 weeks of SOF+ ribavirin for pre‐LT anti‐HCV treatment versus on‐demand post‐LT SOC antiviral therapy. Among the 1794 patients undergoing LT, 860 (48%) were HCV+ and 50% of them were given SOC therapy after LT (mean cost of drugs and adverse effect management = 14 421€ per patient). HCV etiology had a strong impact on post‐LT survival (hazard ratio = 1.59, 95% CI = 1.22–2.09, P = 0.0007). After Monte Carlo simulation, pre‐LT SOF therapy showed a median survival benefit of 1.5 quality‐adjusted life years and an Incremental cost‐effectiveness ratio (ICER) of 30 663€/QALY, proving cost‐effective in our particular Italian scenario. The costs of SOF therapy, sustained viral response rate 12 weeks after LT, and recipient's age were the main ICER predictors at multivariate analysis. This study proposes a dynamic model based on real‐life data from northern Italy for adjusting the costs of pre‐LT direct‐acting antiviral therapies to the actual sustained virological response reached after LT.
Survival and activity of Pseudomonas sp. strain B13(FR1) in a marine microcosm determined by quantitative PCR and an rRNA-targeting probe and its effect on the indigenous bacterioplankton

Genetically engineered Pseudomonas sp. strain B13(FR1) was released into laboratory-scale marine ecosystem models (microcosms). Survival of the introduced population in the water column and the sediment was determined by plating on a selective medium and by quantitative competitive PCR. The activity of the released bacteria was determined by in situ hybridization of single cells with a specific rRNA-targeting oligonucleotide probe. Two microcosms were inoculated with 10(6) cells ml-1, while an uninoculated microcosm served as a control. The number of Pseudomonas sp. strain B13(FR1) cells decreased rapidly to ca. 10(2) cells ml-1 within 2 days after the release, which is indicative of grazing by protozoa. Three days after the introduction into seawater, cells were unculturable, but PCR continued to detect cells in low numbers. Immediately after the release, the ribosomal content of Pseudomonas sp. strain B13(FR1) corresponded to a generation time of 2 h. The growth rate decreased to less than 0.04 h-1 in 5 days and remained low, probably because of carbon limitation of the cells. Specific amendment of the microcosms with 10 mM 4-chlorobenzoate resulted in a rapid increase of the growth rate and an exponentially increasing number of cells detected by PCR, but not in resuscitation of the cells to a culturable state. The release of Pseudomonas sp. strain B13(FR1) into the microcosms seemed to affect only the indigenous bacterioplankton community transiently. Effects on the community were also apparent from the handling of water during filling of the microcosms and the amendment with 4-chlorobenzoate.
Population Genetic Analysis of the Protease Locus of Human Immunodeficiency Virus Type 1 Quasispecies Undergoing Drug Selection, Using a Denaturing Gradient-Heteroduplex Tracking Assay

ABSTRACT Monitoring the evolution of human immunodeficiency virus type 1 (HIV-1) drug resistance requires measuring the frequency of closely related genetic variants making up the complex viral quasispecies found in vivo. In order to resolve both major and minor (≥2%) protease gene variants differing by one or more nucleotide substitutions, we analyzed PCR products derived from plasma viral quasispecies by using a combination of denaturing gradient gel electrophoresis and DNA heteroduplex tracking assays. Correct population sampling of the high level of genetic diversity present within viral quasispecies could be documented by parallel analysis of duplicate, independently generated PCR products. The composition of genetically complex protease gene quasispecies remained constant over short periods of time in the absence of treatment and while plasma viremia fell >100-fold following the initiation of protease inhibitor ritonavir monotherapy. Within a month of initiating therapy, a strong reduction in the genetic diversity of plasma viral populations at the selected protease locus was associated with rising plasma viremia and the emergence of drug resistance. The high levels of protease genetic diversity seen before treatment reemerged only months later. In one patient, reduction in genetic diversity at the protease gene was observed concomitantly with an increase in diversity at the envelope gene (E. L. Delwart, P. Heng, A. Neumann, and M. Markowitz, J. Virol. 72:2416-2421, 1998), indicating that opposite population genetic changes can take place in different HIV-1 loci. The rapid emergence of drug-resistant HIV-1 was therefore associated with a strong, although only transient, reduction in genetic diversity at the selected locus. The denaturing gradient-heteroduplex tracking assay is a simple method for the separation and quantitation of very closely related, low-frequency, genetic variants within complex viral populations.