Miracle-dz/UniFAR-FTUs huggingface dataset:
Denosumab and bone metastasis-free survival in men with nonmetastatic castration-resistant prostate cancer: exploratory analyses by baseline prostate-specific antigen doubling time.

PURPOSE Denosumab, an anti-RANK ligand monoclonal antibody, significantly increases bone metastasis-free survival (BMFS; hazard ratio [HR], 0.85; P = .028) and delays time to first bone metastasis in men with nonmetastatic castration-resistant prostate cancer (CRPC) and baseline prostate-specific antigen (PSA) ≥ 8.0 ng/mL and/or PSA doubling time (PSADT) ≤ 10.0 months. To identify men at greatest risk for bone metastasis or death, we evaluated relationships between PSA and PSADT with BMFS in the placebo group and the efficacy and safety of denosumab in men with PSADT ≤ 10, ≤ 6, and ≤ 4 months. PATIENTS AND METHODS A total of 1,432 men with nonmetastatic CRPC were randomly assigned 1:1 to monthly subcutaneous denosumab 120 mg or placebo. Enrollment began February 2006; primary analysis cutoff was July 2010, when approximately 660 men were anticipated to have developed bone metastases or died. RESULTS In the placebo group, shorter BMFS was observed as PSADT decreased below 8 months. In analyses by shorter baseline PSADT, denosumab consistently increased BMFS by a median of 6.0, 7.2, and 7.5 months among men with PSADT ≤ 10 (HR, 0.84; P = .042), ≤ 6 (HR, 0.77; P = .006), and ≤ 4 months (HR, 0.71; P = .004), respectively. Denosumab also consistently increased time to bone metastasis by PSADT subset. No difference in survival was observed between treatment groups for the overall study population or PSADT subsets. CONCLUSION Patients with shorter PSADT are at greater risk for bone metastasis or death. Denosumab consistently improves BMFS in men with shorter PSADT and seems to have the greatest treatment effects in men at high risk for progression.
Endocannabinoid tone versus constitutive activity of cannabinoid receptors

This review evaluates the cellular mechanisms of constitutive activity of the cannabinoid (CB) receptors, its reversal by inverse agonists, and discusses the pitfalls and problems in the interpretation of the research data. The notion is presented that endogenously produced anandamide (AEA) and 2‐arachidonoylglycerol (2‐AG) serve as autocrine or paracrine stimulators of the CB receptors, giving the appearance of constitutive activity. It is proposed that one cannot interpret inverse agonist studies without inference to the receptors' environment vis‐à‐vis the endocannabinoid agonists which themselves are highly lipophilic compounds with a preference for membranes. The endocannabinoid tone is governed by a combination of synthetic pathways and inactivation involving transport and degradation. The synthesis and degradation of 2‐AG is well characterized, and 2‐AG has been strongly implicated in retrograde signalling in neurons. Data implicating endocannabinoids in paracrine regulation have been described. Endocannabinoid ligands can traverse the cell's interior and potentially be stored on fatty acid‐binding proteins (FABPs). Molecular modelling predicts that the endocannabinoids derived from membrane phospholipids can laterally diffuse to enter the CB receptor from the lipid bilayer. Considering that endocannabinoid signalling to CB receptors is a much more likely scenario than is receptor activation in the absence of agonist ligands, researchers are advised to refrain from assuming constitutive activity except for experimental models known to be devoid of endocannabinoid ligands.
Substrate Specificity of the Arabidopsis thaliana Sucrose Transporter AtSUC2*

The Arabidopsis sucrose transporter AtSUC2 is expressed in the companion cells of the phloem (specialized vascular tissue) and is essential for the long distance transport of carbohydrates within the plant. A variety of glucosides are known to inhibit sucrose uptake into yeast expressing AtSUC2; however, it remains unknown whether glucosides other than sucrose could serve as transported substrates. By expression of AtSUC2 in Xenopus oocytes and two-electrode voltage clamping, we have tested the ability of AtSUC2 to transport a range of physiological and synthetic glucosides. Sucrose induced inward currents with a K0.5 of 1.44 mm at pH 5 and a membrane potential of –137 mV. Of the 24 additional sugars tested, 8 glucosides induced large inward currents allowing kinetic analysis. These glucosides were maltose, arbutin (hydroquinone-β-d-glucoside), salicin (2-(hydroxymethyl)phenyl-β-d-glucoside), α-phenylglucoside, β-phenylglucoside, α-paranitrophenylglucoside, β-paranitrophenylglucoside, and paranitrophenyl-β-thioglucoside. In addition, turanose and α-methylglucoside induced small but significant inward currents indicating that they were transported by At-SUC2. The results indicate that AtSUC2 is not highly selective for α-over β-glucosides and may function in transporting glucosides besides sucrose into the phloem, and the results provide insight into the structural requirements for transport by AtSUC2.
Pilot Evaluation of a Media Literacy Program for Tobacco Prevention Targeting Early Adolescents Shows Mixed Results

Purpose. The purpose of this pilot study was to assess the impact of media literacy for tobacco prevention for youth delivered through a community site. Design. A randomized pretest-posttest evaluation design with matched-contact treatment and control conditions. Setting. The pilot study was delivered through the YMCA in a lower-income suburban and rural area of Southwest Virginia, a region long tied, both economically and culturally, to the tobacco industry. Subjects. Children ages 8 to 14 (76% white, 58% female) participated in the study (n = 38). Intervention. The intervention was an antismoking media literacy program (five 1-hour lessons) compared with a matched-contact creative writing control program. Measures. General media literacy, three domains of tobacco-specific media literacy (“authors and audiences,” “messages and meanings,” and “representation and reality”), tobacco attitudes, and future expectations were assessed. Analysis. Multiple regression modeling assessed the impact of the intervention, controlling for pretest measures, age, and sex. Results. General media literacy and tobacco-specific “authors and audiences” media literacy improved significantly for treatment compared with control (p < .05); results for other tobacco-specific media literacy measures and for tobacco attitudes were not significant. Future expectations of smoking increased significantly for treatment participants ages 10 and younger (p < .05). Conclusion. Mixed results indicated that improvements in media literacy are accompanied by an increase in future expectations to smoke for younger children.
A model of EMG generation

Simulation models are unavoidable in experimental research when the point is to develop new processing algorithms to be applied on real signals in order to extract specific parameter values. Such algorithms have generally to be optimized by comparing true parameter values to those deduced from the algorithm. Only a simulation model can allow the user to access and control the actual process parameter values. This constraint is especially true when dealing with biomedical signals like surface electromyogram (SEMG). This work is an attempt to produce an efficient SEMG simulation model as a help for assessing algorithms related to SEMG features description. It takes into account the most important parameters which could influence these characteristics. This model includes all transformations from intracellular potential to surface recordings as well as a fast implementation of the extracellular potential computation. In addition, this model allows multiple graphically-programmable electrode-set configurations and SEMG simulation in both voluntary and elicited contractions.
Harmonic algorithm for 3-dimensional strip packing problem

In the three dimensional strip packing problem, we are given a set of three-dimensional rectangular items <i>I</i> = {(<i>x<inf>i</inf>, y<inf>i</inf>, z<inf>i</inf></i>) : <i>i</i> = 1, . , <i>n</i>} and a three dimensional box <i>B</i>. The goal is to pack all the items in the box <i>B</i> without any overlap, such that the height of the packing is minimized. We consider the most basic version of the problem, where the items must be packed with their edges parallel to the edges of <i>B</i> and cannot be rotated. Building upon Caprara's work [4] for the two dimensional bin packing problem we obtain an approximation algorithm with a similar performance guarantee of <i>T</i><inf>∞</inf> ≈ 1.69 where <i>T</i><inf>∞</inf> is the well known Harmonic number that occurs naturally in the context of bin packing. The previously known approximation algorithms for this problem had worst case performance guarantees of 2 [7], 2.64 [14], 2.67 [15], 2.89 [10] and 3.25 [11]. Our second algorithm is an asymptotic PTAS for the case in which all items have <i>square</i> bases.
Assessment of Bone Quality using Finite Element Analysis Based upon Micro-CT Images

Background To evaluate the feasibility of a micro-image based finite element model to determine the efficacy of sequential treatments on the bone quality in a rat osteoporosis model. Methods Rat osteoporosis and treated osteoporosis models were established with the bone loss, restore and maintain concept. Thirty Sprague-Dawley rats were used in this study. A sham operation or ovariectomy was performed at 20 weeks after birth, which was followed by the respective sequential trials as follows: (1) sham-operation only, (2) ovariectomy only, (3) ovariectomized rats with parathyroid hormone maintenance, (4) ovariectomized rats treated with PTH for 5 weeks and then withdrawal, (5) ovariectomized rats treated with PTH for 5 weeks and then with 17 beta-estradiol, and (6) ovariectomized rats treated with parathyroid hormone for 5 weeks and then treated with zoledronate. The histomorphometry indices were determined using the micro-images from a micro-computed tomogram. Finite element analysis was carried out to determine the mechanical properties (Stiffness and Young's modulus) of the vertebra bodies. The differences in properties between the groups were compared using ANOVA and a Bonferroni's multiple group comparison procedure. Results The histomorphometry and mechanical properties were significantly better in groups (3) and (6) than in the groups (1) and (2) (p < 0.05). The stiffness (σs) and Young's modulus (E) was highest in group (3) following by group (6). Conclusions Finite element analysis based on micro-images provides a useful tool that reflects the changes in micro-structural and mechanical properties of a rat vertebral body with the bone loss, restore and maintain concept.
Genome-wide Characterization of Shared and Distinct Genetic Components That Influence Blood Lipid Levels in Ethnically Diverse Human Populations

Blood lipid concentrations are heritable risk factors associated with atherosclerosis and cardiovascular diseases. Lipid traits exhibit considerable variation among populations of distinct ancestral origin as well as between individuals within a population. We performed association analyses to identify genetic loci influencing lipid concentrations in African American and Hispanic American women in the Women's Health Initiative SNP Health Association Resource. We validated one African-specific high-density lipoprotein cholesterol locus at CD36 as well as 14 known lipid loci that have been previously implicated in studies of European populations. Moreover, we demonstrate striking similarities in genetic architecture (loci influencing the trait, direction and magnitude of genetic effects, and proportions of phenotypic variation explained) of lipid traits across populations. In particular, we found that a disproportionate fraction of lipid variation in African Americans and Hispanic Americans can be attributed to genomic loci exhibiting statistical evidence of association in Europeans, even though the precise genes and variants remain unknown. At the same time, we found substantial allelic heterogeneity within shared loci, characterized both by population-specific rare variants and variants shared among multiple populations that occur at disparate frequencies. The allelic heterogeneity emphasizes the importance of including diverse populations in future genetic association studies of complex traits such as lipids; furthermore, the overlap in lipid loci across populations of diverse ancestral origin argues that additional knowledge can be gleaned from multiple populations.
Effect of the amount of thickness reduction on color and translucency of dental monolithic zirconia ceramics

PURPOSE This study investigated the effect of amount of thickness reduction on color and translucency of dental monolithic zirconia ceramics. MATERIALS AND METHODS One-hundred sixty-five monolithic zirconia specimens (16.3 mm × 16.3 mm × 2.0 mm) were divided into 5 groups (Group I to V) according to the number of A2-coloring liquid applications. Each group was then divided into 11 subgroups by reducing the thickness up to 1.0 mm in 0.1-mm increments (Subgroup 0 to 10, n=3). Colors and spectral distributions were measured according to CIELAB on a reflection spectrophotometer. All measurements were performed on five different areas of each specimen. Color difference (ΔE*ab) and translucency parameter (TP) were calculated. Data were analyzed using one-way ANOVA and multiple comparison Scheffé test (α=.05). RESULTS There were significant differences in CIE L* between Subgroup 0 and other subgroups in all groups. CIE a* increased (0.523.7) were obtained between Subgroup 0 and other subgroups. TP values generally increased as the thickness reduction increased in all groups (R2>0.89, P<.001). CONCLUSION Increasing thickness reduction reduces lightness and increases a reddish, bluish appearance, and translucency of monolithic zirconia ceramics.
Epidemiologic and Drug Resistance Pattern of Vibrio cholerae O1 Biotype El Tor, Serotype Ogawa, in the 2011 Cholera Outbreak, in Alborz Province, Iran

Background: Although the national guidelines recommend special antibiotics, based on the antibiogram of National Reference Laboratory, it seems that, because of uncontrolled usage of antibiotics in the society and due to the changes in the serotypes causing the disease, it is essential to monitor the status of drug resistance, permanently, and to revise the current prescriptions guidelines. Objectives: This study aimed to assess the epidemiological aspects and drug resistance pattern of Vibrio cholerae O1, biotype El Tor, serotype Ogawa, in cholera outbreak, in Alborz province in Iran, during 2011. Materials and Methods: This is a cross-sectional study, which reviews a cholera epidemic that occurred in Iran. A total of 9844 specimens were taken from suspected cases, among diarrheal patients, via rectal swabs. The specimens were placed in Cary-Blair transport medium and sent to laboratory. Samples were enriched, in alkaline peptone water, and isolated on thiosulphate-citrate-bile salt-sucrose agar. From the 244 confirmed cases, 239 cases underwent antibiogram test, via disk diffusion method and based on national committee for clinical laboratory standards (NCCLS) instructions. The standard Escherichia coli ATCC 25922 was used for antibiogram quality control and, eventually, all results were interpreted and reported using NCCLS standard table. Results: In total, until October 22, 2011, which was announced as the end of outbreak, 9844 samples were taken from diarrheal patients. Regarding the type of V. cholerae, 244 El Tor biotype positive cases were reported. The case fatality rate was 1.3%. The mean age of patients was 37.8 years and the highest incidence rate occurred in the age group 21 - 30 years. After conducting antibiotic susceptibility test in the 244 V. cholerae, biotype El Tor, serotype Ogawa, it was found that ciprofloxacin had the highest level of antibiotic susceptibility (99.6%) and the highest level of antibiotic resistance was observed in co-trimoxazole (95.4%). Conclusions: The results of our study show that the resistances to doxycycline and tetracycline, which are mentioned in multiple resources, as the most common antibiotic drugs for treating cholera, are increasing.
Sipuleucel-T: harbinger of a new age of therapeutics for prostate cancer

Sipuleucel-T (Provenge®) is the first therapeutic cancer vaccine approved by the US FDA. The approval heralds the long-awaited promise of improved patient survival with minimal toxicity by therapies designed to generate an active, specific anticancer immune response. The development of this first-in-class agent as well as other therapeutic vaccines in clinical evaluation has also led to a better understanding of relevant patient populations and end points for clinical trials. This article discusses the development and approval of sipuleucel-T in the context of other approved therapies for prostate cancer, as well as controversies and novel paradigms brought about by this new agent.
OPTIMAL CONTROL OF A PRODUCTION SYSTEM WITH INFORMATION ON THE PRODUCTION AND DEMAND STATUS: APPLICATION TO VENDOR MANAGED INVENTORY

we consider a system consisting of a manufacturer serving several retailers. The manufacturer produces a standard product in a make-to-stock fashion in anticipation of orders emanating from n retailers. Orders from the retailers arrive in batches which sizes follow a discrete distribution. The production time is assumed to follow a k0- Erlang distribution. Order inter-arrival time for class l demand is assumed to follow a kl-Erlang distribution. Work-in- process as well as finished units incur a per unit per unit of time carrying cost. Unsatisfied units from an order from a particular retailer are assumed lost and incur a retailer-specific lost sale cost. The objective is to determine the optimal production and inventory allocation policies so as to minimize the expected total cost. We show that the optimal pro- duction policy is of the base-stock type with base-stock levels non-decreasing in the demand stages. We also show that the optimal inventory allocation policy among retailers is a rationing policy with rationing levels non-decreasing in the demand stages. We offer managerial insights such as the effect of variability on the operating cost and the benefits of such contracts as VMI or CPFR.
Intraocular Pressure Changes: An Important Determinant of the Biocompatibility of Intravitreous Implants

Background In recent years, research efforts exploring the possibility of using biomaterial nanoparticles for intravitreous drug delivery has increased significantly. However, little is known about the effect of material properties on intravitreous tissue responses. Principal Findings To find the answer, nanoparticles made of hyaluronic acid (HA), poly (l-lactic acid) (PLLA), polystyrene (PS), and Poly N-isopropyl acrylamide (PNIPAM) were tested using intravitreous rabbit implantation model. Shortly after implantation, we found that most of the implants accumulated in the trabecular meshwork area followed by clearance from the vitreous. Interestingly, substantial reduction of intraocular pressure (IOP) was observed in eyes implanted with particles made of PS, PNIPAM and PLLA, but not HA nanoparticles and buffered salt solution control. On the other hand, based on histology, we found that the particle implantation had no influence on cornea, iris and even retina. Surprisingly, substantial CD11b+ inflammatory cells were found to accumulate in the trabecular meshwork area in some animals. In addition, there was a good relationship between recruited CD11b+ cells and IOP reduction. Conclusions Overall, the results reveal the potential influence of nanoparticle material properties on IOP reduction and inflammatory responses in trabecular meshwork. Such interactions may be critical for the development of future ocular nanodevices with improved safety and perhaps efficacy.
Brachial-ankle pulse wave velocity and rate of renal function decline and mortality in chronic kidney disease.

BACKGROUND AND OBJECTIVES Increased arterial stiffness was reported to be associated with decreased estimated GFR (eGFR). Previous studies suggested that arterial stiffness might play a role in renal function progression in patients with chronic kidney disease (CKD). The aim of this study was to investigate whether there was an independent association between brachial-ankle pulse wave velocity (baPWV), a marker of arterial stiffness, and renal function progression in CKD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This longitudinal study enrolled 145 patients with CKD stages 3 to 5. The baPWV was measured by using an ABI-form device. The change in renal function was estimated by eGFR slope. The study endpoints were defined as commencement of dialysis or death. RESULTS After a stepwise multivariate analysis, the eGFR slope was positively associated with baseline eGFR and negatively associated with hypertension and baPWV (β=-0.165, P=0.033). Seventeen patients entering dialysis, and eight deaths were recorded. Multivariate forward Cox regression analysis identified that higher baPWV (hazard ratio, 1.001; P=0.001), lower baseline eGFR, and higher serum phosphate level were independently associated with progression to commencement of dialysis or death. CONCLUSIONS Our results show an independent association between baPWV and renal function decline and progression to commencement of dialysis or death in patients with CKD. Screening CKD patients by means of baPWV may help identify a high-risk group of rapid renal function decline and progression to commencing dialysis or death.
A case of exercise-induced sinus node deceleration without evident coronary artery disease.

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