Miracle-dz/UniFAR-FTUs huggingface dataset:
The SF-36 Health Survey as a generic outcome measure in clinical trials of patients with osteoarthritis and rheumatoid arthritis: relative validity of scales in relation to clinical measures of arthritis severity.

OBJECTIVE To evaluate the validity of SF-36 Health Survey (SF-36) scale scores and summary measure scores to describe the health burden of arthritis and to be responsive to clinical indicators of arthritis severity used in four clinical trials. METHODS Adults participating in four double-blinded, placebo-controlled clinical trials of therapy for osteoarthritis or rheumatoid arthritis were administered the SF-36 concurrent with clinical measures of disease severity (n = 1,016). Data were collected before treatment and 2 weeks after treatment. Mean SF-36 scores for all patients with arthritis at baseline were compared to a sociodemographically equivalent national norm to test the ability of the SF-36 to describe the burden of arthritis. To test the responsiveness of SF-36 scores to clinical measures of arthritis severity, mean SF-36 scale scores were compared across patients differing in arthritis severity before treatment. Two-week mean SF-36 change scores were compared across patients who improved in arthritis severity (responders) versus patients who did not improve (nonresponders). F-statistics and relative validity coefficients were computed to determine how well each SF-36 scale and summary measure discriminated among arthritis severity levels and distinguished treatment responders from nonresponders, relative to the best scale. RESULTS Large and statistically significant differences in mean SF-36 scale scores and summary measures were found such that trial participants scored in worse health than a sociodemographically equivalent US general population norm. In addition, the largest SF-36 scale scores were found to significantly differ across clinically defined levels of arthritis severity. Finally, it was found that the SF-36 scales that best discriminate among arthritis severity groups cross-sectionally were also best at discriminating treatment responders from nonresponders. CONCLUSION Results of this study support the validity of the SF-36 to document the health burden of arthritis and as a measure of generic health outcome for clinical trials of alternative treatments for osteoarthritis and rheumatoid arthritis patients.
Supplementary Material : Synthesized Classifiers for Zero-Shot Learning

There are a few free hyper-parameters in our approach (cf. Section 3.2 of the main text). To choose the hyper-parameters in the conventional cross-validation (CV) for multi-way classification, one splits the training data into several folds such that they share the same set of class labels with one another. Clearly, this strategy is not sensible for zero-shot learning as it does not imitate what actually happens at the test stage. We thus introduce a new strategy for performing CV, inspired by the hyper-parameter tuning in [24]. The key difference of the new scheme to the conventional CV is that we split the data into several folds such that the class labels of these folds are disjoint. For clarity, we denote the conventional CV as sample-wise CV and our scheme as class-wise CV. Figure 1(b) and 1(c) illustrate the two scenarios, respectively. We empirically compare them in Section 5.1. Note that several existing models [2, 6, 24, 33] also follow similar hyper-prameter tuning procedures.
Local and Global Convergence of an Inertial Version of Forward-Backward Splitting

A problem of great interest in optimization is to minimize a sum of two closed, proper, and convex functions where one is smooth and the other has a computationally inexpensive proximal operator. In this paper we analyze a family of Inertial Forward-Backward Splitting (I-FBS) algorithms for solving this problem. We first apply a global Lyapunov analysis to I-FBS and prove weak convergence of the iterates to a minimizer in a real Hilbert space. We then show that the algorithms achieve local linear convergence for "sparse optimization", which is the important special case where the nonsmooth term is the $\ell_1$-norm. This result holds under either a restricted strong convexity or a strict complimentary condition and we do not require the objective to be strictly convex. For certain parameter choices we determine an upper bound on the number of iterations until the iterates are confined on a manifold containing the solution set and linear convergence holds. The local linear convergence result for sparse optimization holds for the Fast Iterative Shrinkage and Soft Thresholding Algorithm (FISTA) due to Beck and Teboulle which is a particular parameter choice for I-FBS. In spite of its optimal global objective function convergence rate, we show that FISTA is not optimal for sparse optimization with respect to the local convergence rate. We determine the locally optimal parameter choice for the I-FBS family. Finally we propose a method which inherits the excellent global rate of FISTA but also has excellent local rate.
Safety and Immunogenicity of a Meningococcal B Bivalent rLP2086 Vaccine in Healthy Toddlers Aged 18–36 Months: A Phase 1 Randomized-controlled Clinical Trial

Background: A bivalent, recombinant, factor H–binding protein (rLP2086) vaccine was developed to protect against invasive Neisseria meningitidis serogroup B (MnB) in children and adolescents. Methods: Healthy toddlers (N = 99) were enrolled to 3 ascending dose-level cohorts (20, 60 or 200 &mgr;g). Within each cohort (n = 33), subjects were randomized to receive an initial formulation of the bivalent rLP2086 vaccine at 0, 1 and 6 months or hepatitis A vaccine/placebo control (2:1 ratio). Reactogenicity was assessed by parental reporting of local and systemic reactions using electronic diaries and reports of unsolicited adverse events. Immunogenicity was assessed by serum bactericidal activity assay using human complement and rLP2086-specific IgG binding. Results: The vaccine was considered to be well tolerated. Tenderness was the most frequently reported local reaction. Upper respiratory tract infection was the most commonly reported adverse event and occurred more frequently in the control group. Three cases (200 &mgr;g dose) of severe erythema that did not interfere with limb movement were reported. Four toddlers developed fever >40.0°C, 3 in the 200 &mgr;g group and 1 in the 60 &mgr;g group. Postdose 3, seroconversion (serum bactericidal activity assay using human complement ≥4-fold rise from baseline) was observed in 61.1–88.9% of participants against MnB strains expressing LP2086 variants homologous or nearly homologous to vaccine antigens and 11.1–44.4% against MnB strains expressing heterologous LP2086 variants. Seroconversion was observed in 77.8–100% of participants against additional, exploratory MnB strains expressing vaccine-homologous or heterologous LP2086 variants. Conclusions: This study shows that the bivalent rLP2086 vaccine is well tolerated and immunogenic in toddlers.
The Simulation Spreading Process of Steel Tubes Hollow

The paper presents finite element analysis of spreading process of hollow steel tubes implemented within commercial software MES FORGE2-V3.0. To this purpose, rigid-plastic model of deformed material was assumed. The analysis was realised for hollow tube made from steel C45 with external diameter D0 = 50 mm and internal one d0 = 40 mm. Distributions of temperature, stress and deformation for different values of gradient radius of mandrel  (1535) and different friction conditions on the area of metal-tool were determined. With the piercing press the billet is introduced into a vertical or horizontal die, subsequently to be pierced by mandrel. Afterwards pipe is elongated in Diescher’s mill. Hollow steel tubes undergo hot deformation spreading process in two-roll press by mandrel. Process stability depends on dimensions of the hollow tube and mandrel: tube external diameter, tube internal diameter, mandrel diameter and inclination angle of mandrel. Increase of external diameter of hollow tube occurs in the course of spreading process by mandrel. Process parameters depend on chemical composition and type of material. In this paper the contact problem in metal – tool interface is considered. Burnishing implies the sizing of a hollow tube by its plastic spreading.
Vitamin D status is inversely associated with anemia and serum erythropoietin during pregnancy.

BACKGROUND Vitamin D and iron deficiencies frequently co-exist. It is now appreciated that mechanistic interactions between iron and vitamin D metabolism may underlie these associations. OBJECTIVE We examined interrelations between iron and vitamin D status and their regulatory hormones in pregnant adolescents, who are a group at risk of both suboptimal vitamin D and suboptimal iron status. DESIGN The trial was a prospective longitudinal study of 158 pregnant adolescents (aged ≤18 y). Maternal circulating biomarkers of vitamin D and iron were determined at midgestation (∼25 wk) and delivery (∼40 wk). Linear regression was used to assess associations between vitamin D and iron status indicators. Bivariate and multivariate logistic regressions were used to generate the OR of anemia as a function of vitamin D status. A mediation analysis was performed to examine direct and indirect relations between vitamin D status, hemoglobin, and erythropoietin in maternal serum. RESULTS Maternal 25-hydroxyvitamin D [25(OH)D] was positively associated with maternal hemoglobin at both midgestation and at delivery (P < 0.01 for both). After adjustment for age at enrollment and race, the odds of anemia at delivery was 8 times greater in adolescents with delivery 25(OH)D concentrations <50 nmol/L than in those with 25(OH)D concentrations ≥50 nmol/L (P <0.001). Maternal 25(OH)D was inversely associated with erythropoietin at both midgestation (P <0.05) and delivery (P <0.001). The significant relation observed between 25(OH)D and hemoglobin could be explained by a direct relation between 25(OH)D and hemoglobin and an indirect relation that was mediated by erythropoietin. CONCLUSIONS In this group of pregnant adolescents, suboptimal vitamin D status was associated with increased risk of iron insufficiency and vice versa. These findings emphasize the need for screening for multiple nutrient deficiencies during pregnancy and greater attention to overlapping metabolic pathways when selecting prenatal supplementation regimens.
The effects of combined free radical scavenger and sildenafil therapy on age-associated erectile dysfunction: An animal model

Introduction: Aging results in erectile dysfunction that is partially attributed to decreased nitric oxide (NO) and increased free radical generation. Vitamin E enhances endothelial cell function and acts as a free radical scavenger; however, its benefits on erectile function in the elderly are unknown. Aims: The aim of the following study is to determine if Vitamin E alone, or in combination with the phosphodiesterase 5 inhibitor sildenafil, may improve erectile function and the NO signaling in a cohort of aged (13-15 month old) rats. Materials and Methods: Male Sprague-Dawley rats (n = 28) were divided based upon age into young (4-5 months old, n = 7) and aged (13-15 months old, n = 21) cohorts. Aged rats were treated with Vitamin E, sildenafil or a combination of both. Penile cavernosal and dorsal nerve tissues were evaluated for neuronal nitric oxide synthase (nNOS) and caveolin-1 expression. Erectile function was assessed through intra-cavernous pressure (ICP) recordings. Results: nNOS and cavoelin-1 were significantly decreased in aged rats compared with young controls. In aged rats, both Vitamin E and sildenafil partially recovered nNOS expression but when combined, a synergistic elevation in nNOS was observed. The significant decreases in ICP recorded in aged rats were improved with sildenafil; however, Vitamin E did not yield any additional improvements in ICP. Conclusions: Diminished levels of nNOS and caveolin-1 are found in aged rats. When combined with sildenafil, Vitamin E synergistically increased nNOS expression. Since biochemical gains were not realized physiologically, other contributing factors likely exist.
Expression of TMEM166 Protein in Human Normal and Tumor Tissues

Transmembrane protein 166 (TMEM166) is a novel human regulator involved in both autophagy and apoptosis. In this study, we generated a specific rabbit polyclonal antibody against human TMEM166 and assessed the expression of this protein in various human normal and tumor tissue samples by tissue microarray-based immunohistochemical analysis. Varying TMEM166 protein levels were expressed in a cell-type and tissue-type–specific manner in detected tissues or organs. Strong TMEM166 expression was shown in the glomerular zona of the adrenal cortex, chromophil cells of the pituitary gland, islet cells, squamous epithelium of the esophagus mucosa, the fundic gland, and hepatocytes. Moderate or weak TMEM166 staining was identified in the parathyroid gland, the testis, vaginal stratified squamous cells, lung macrophages, hematopoietic cells, renal tubular epithelial cells, macrophages in the spleen red pulp, and neuronal cells in the cerebral cortex. Some tissues failed to stain for TMEM166, such as adipose tissue, colon, cerebellum, lymph node, mammary gland, ovary, prostate, rectum, skin, small intestine, thyroid gland, tonsil, and thymus. In comparing human normal and tumor tissues, TMEM166 expression was widely downregulated in the cancer tissues. Our studies provide the basis for future investigations into cell-type–specific functions of this protein in human normal and tumor tissues.
Poliovirus Requires a Precise 5′ End for Efficient Positive-Strand RNA Synthesis

ABSTRACT Poliovirus infectious RNA can be synthesized in vitro using phage DNA-dependent RNA-polymerases. These synthetic transcripts contain several extra nucleotides at the 5′ end, which are deleted during replication to generate authentic viral genomes. We removed those 5′-end extra nucleotides utilizing a hammerhead ribozyme to produce transcripts with accurate 5′ ends. These transcripts replicate substantially more rapidly in cell culture, demonstrating no lag before replication; they also replicate more efficiently in Xenopus laevis oocytes and in in vitro translation-replication cell extracts. In both systems, an exact 5′ end is necessary for synthesis of positive-strand RNA but not negative-strand RNA.
An evaluation of earcons for use in auditory human-computer interfaces

An evaluation of earcons was carried out to see whether they are an effective means of communicating information in sound. An initial experiment showed that earcons were better than unstructured bursts of sound and that musical timbres were more effective than simple tones. A second experiment was then carried out which improved upon some of the weaknesses shown up in Experiment 1 to give a significant improvement in recognition. From the results of these experiments some guidelines were drawn up for use in the creation of earcons. Earcons have been shown to be an effective method for communicating information in a human-computer interface.
Nanoengineered polyelectrolyte micro- and nano-capsules as fluorescent potassium ion sensors.

Hollow polyelectrolyte capsules have been fabricated and initial experiments have shown their functionality as biosensors, with potassium ions as a sample analyte. Sensors such as these could be employed in basic research, such as in monitoring cells in culture, as well as diagnostic tools in medicine. The sensors can monitor real-time potassium ion transients with high sensitivity due to the packaging of many probe molecules in a small volume. Further work on addition of coatings with biocompatible properties or selective binding molecules (e.g. antibodies) may enable employment of these systems in a broader range of applications.
Generalized (, b, ϕ, ρ, θ)-univex n-set functions and global parametric sufficient optimality conditions in minmax fractional subset programming

We first define a new class of generalized convex n-set functions, called (𝔉,b,ϕ,ρ,θ)-univex functions, and then establish a fairly large number of global parametric sufficient optimality conditions under a variety of generalized (𝔉,b,ϕ,ρ,θ)-univexity assumptions for a discrete minmax fractional subset programming problem.
during Viral Infections but Does Not Affect CD8 T Cell Responses MHC Class I Presentation in Dendritic Cells Puromycin-Sensitive Aminopeptidase Limits

Previous experiments using enzyme inhibitors, cell lysates, and puriﬁed enzyme have suggested that puromycin-sensitive aminopeptidase (PSA) plays a role in creating and destroying MHC class I-presented peptides although its precise contribution to these processes is unknown. To examine the importance of this enzyme in MHC class I Ag presentation, we have generated PSA-deﬁcient mice and cell lines from these animals. PSA-deﬁcient mice are smaller and do not reproduce as well as wild type mice. In addition, dendritic cells from PSA-deﬁcient mice display more MHC class I molecules on the cell surface, suggesting that PSA normally limits Ag presentation by destroying certain peptides in these key APCs. Surprisingly, MHC class I levels are not altered on other PSA-deﬁcient cells and the processing and presentation of peptide precursors in PSA-deﬁcient ﬁbroblasts is normal. Moreover, PSA-deﬁcient mice have normal numbers of T cells in the periphery, and respond as well as wild type mice to eight epitopes from three viruses. These data indicate that PSA may play a role in limiting MHC class I Ag presentation in dendritic cells in vivo but that it is not essential for generating most MHC class I-presented peptides or for stimulating CTL responses to several Ags. The Journal of Immunology, 2008, 180: 1704–1712. a means CTLs intracellular events and assure that pathogens and aberrant cells are recognized and eliminated. The TCR on CTL transiently binds to the MHC-I/peptide complex, and the CTL is activated when an appropriate agonist peptide
Phase I and clinical evaluation of a pharmacologically guided regimen of suramin in patients with hormone-refractory prostate cancer.

PURPOSE This phase I study was designed with the following objectives: (1) to describe the overall and dose-limiting toxicity (DLT) of suramin administered by intermittent short intravenous infusions until DLT or disease progression; (2) to determine the ability of an adaptive control with feedback (ACF) dosing strategy to maintain suramin plasma concentrations within a preselected range; (3) to develop a population model of suramin pharmacokinetics; and (4) to identify preliminary evidence of antitumor activity. PATIENTS AND METHODS Seventy-three patients with advanced, incurable, solid tumors (including 69 with hormone-refractory prostate cancer) received an initial 5- to 7-day daily loading treatment followed by intermittent infusions individually determined by ACF using a Bayesian algorithm and relying on population models of suramin pharmacokinetics. Treatment was given to three cohorts of patients based on target plasma suramin concentration ranges (peak, 30 minutes postsuramin, and trough on morning of the treatment day), as follows: cohort 1, 175 to 300 micrograms/mL (27 patients); cohort 2, 150 to 250 micrograms/mL (23 patients); and cohort 3, 100 to 200 micrograms/mL (23 patients). All patients were to receive suramin until DLT or disease progression. RESULTS The DLT was most commonly seen in cohort 1 and included a syndrome of malaise and fatigue, associated with weight loss, anorexia, and changes in taste. Other reversible toxicities were neurologic, renal, cutaneous, edema, lymphopenia and anemia, ophthalmologic, and alopecia. Forty of 67 assessable patients (60%) had a 50% reduction and 25 of 67 (37%) a 75% reduction in prostate-specific antigen (PSA) levels that lasted more than 4 weeks, seven of 18 (40%) had measurable responses, and 18 of 37 (49%) demonstrated major pain improvement. The overall times to disease progression and survival were 170 and 492 days, respectively. CONCLUSION We have characterized all toxicities with suramin in a pharmacologically guided phase I study designed to maintain plasma suramin concentrations of 100 to 300 micrograms/mL (cohorts 1 to 3). The incidence of grade 3 to 4 neurologic abnormalities was relatively low, particularly in cohorts 2 and 3 (100 to 250 micrograms/mL). Evidence of significant and durable antitumor activity was seen in all three cohorts.
Medical Management to Prevent Recurrent Nephrolithiasis in Adults: A Systematic Review for an American College of Physicians Clinical Guideline

BACKGROUND Optimum management to prevent recurrent kidney stones is uncertain. PURPOSE To evaluate the benefits and harms of interventions to prevent recurrent kidney stones. DATA SOURCES MEDLINE, Cochrane, and other databases through September 2012 and reference lists of systematic reviews and randomized, controlled trials (RCTs). STUDY SELECTION 28 English-language RCTs that studied treatments to prevent recurrent kidney stones and reported stone outcomes. DATA EXTRACTION One reviewer extracted data, a second checked accuracy, and 2 independently rated quality and graded strength of evidence. DATA SYNTHESIS In patients with 1 past calcium stone, low-strength evidence showed that increased fluid intake halved recurrent composite stone risk compared with no treatment (relative risk [RR], 0.45 [95% CI, 0.24 to 0.84]). Low-strength evidence showed that reducing soft-drink consumption decreased recurrent symptomatic stone risk (RR, 0.83 [CI, 0.71 to 0.98]). In patients with multiple past calcium stones, most of whom were receiving increased fluid intake, moderate-strength evidence showed that thiazides (RR, 0.52 [CI, 0.39 to 0.69]), citrates (RR, 0.25 [CI, 0.14 to 0.44]), and allopurinol (RR, 0.59 [CI, 0.42 to 0.84]) each further reduced composite stone recurrence risk compared with placebo or control, although the benefit from allopurinol seemed limited to patients with baseline hyperuricemia or hyperuricosuria. Other baseline biochemistry measures did not allow prediction of treatment efficacy. Low-strength evidence showed that neither citrate nor allopurinol combined with thiazide was superior to thiazide alone. There were few withdrawals among patients with increased fluid intake, many among those with other dietary interventions and more among those who received thiazide and citrate than among control patients. Reporting of adverse events was poor. LIMITATIONS Most trial participants had idiopathic calcium stones. Nearly all studies reported a composite (including asymptomatic) stone recurrence outcome. CONCLUSION In patients with 1 past calcium stone, increased fluid intake reduced recurrence risk. In patients with multiple past calcium stones, addition of thiazide, citrate, or allopurinol further reduced risk. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.
A speed-accuracy trade-off in children's processing of scalar implicatures

Scalar implicatures—inferences from a weak description (“I ate some of the cookies”) that a stronger alternative is not true (“I didn’t eat all”)—are paradigm cases of pragmatic inference. Children’s trouble with scalar implicatures is thus an important puzzle for theories of pragmatic development, given their communicative competence in other domains. Previous research has suggested that access to alternatives might be key. Here, we explore children’s reaction times in a new paradigm for measuring scalar implicature processing. Alongside failures on scalar implicatures with “some,” we replicate previous reports of failures with “none,” and find evidence of a speedaccuracy trade-off for both quantifiers. Motivated by these findings, we explore the relationship between accuracy and reaction time with a Drift Diffusion Model. We find evidence consistent with the hypothesis that preschoolers lack access to relevant alternatives for scalar implicature computation, although this set of alternatives may be broader than previously assumed.