nils-herrmann/clean_scirepeval huggingface dataset:
Efficacy and safety of a novel ĸ-agonist for managing intractable pruritus in dialysis patients.

Our previous placebo-controlled, prospective, double-blind study demonstrated that a new opioid ĸ-receptor agonist, nalfurafine hydrochloride, effectively reduced treatment-resistant pruritus in 337 hemodialysis patients. Thus, we designed this study to evaluate prospectively the efficacy, safety, addiction liability, and pharmacokinetics of nalfurafine given orally for 1 year.



This open-label study examined the effects and adverse drug reactions (ADRs) of 52-week oral administration of nalfurafine hydrochloride (5 µg/day) in 211 hemodialysis patients with a treatment-resistant itch.



Of 211 patients, 145 completed the study as scheduled. The mean pruritus value assessed by the visual analogue scale was 75.2 mm during the pre-observation period, which decreased significantly to 50.9 and 30.9 mm in week 2 and 52, respectively, indicating a long-lasting efficacy. ADRs occurred in 103 patients (48.8%). Frequent ADRs were insomnia (sleep disturbance, 19.4%), constipation (7.1%) and increased blood prolactin (3.3%), similar to previous reports. Regarding addiction liability, it appeared unlikely that nalfurafine hydrochloride was abused. After the start of treatment, plasma drug levels reached a steady state in week 2 with no apparent tendency of systemic accumulation.



Nalfurafine hydrochloride, orally administered at 5 µg/day for 52 weeks to hemodialysis patients, produced a long-term suppression of pruritus without significant safety problems.
Comparison of pre- vs. postmeal administration of miglitol for 3 months in type 2 diabetic patients.

alpha-Glucosidase inhibitors (alphaGIs) primarily modify postprandial plasma glucose levels and should be taken just before meals. We previously demonstrated that a single administration of miglitol within 30 min after the start of a meal was equally effective as when administered just before a meal. We here compared pre- vs. postmeal administration of miglitol for 3 months in type 2 diabetic patients.



Thirty-one type 2 diabetic outpatients who had never been treated with insulin injections or alphaGIs were randomized to two groups: patients in group A were asked to take miglitol just before meals, while patients in group B were asked to take miglitol after meals. We measured 1,5-anhydroglucitol (1,5-AG) and HbA(1C) levels in these patients.



The administration of miglitol after meals for a 3-month period decreased HbA(1C) and increased 1,5-AG levels to the same extent as when administered just before meals. The incidence of adverse effects seemed to be unrelated to the timing of the miglitol administration.



Our results suggest that if patients have difficulty remembering to take miglitol just before meal, they should be instructed to take the medicine together with other medicine(s) after the meal; this instruction may improve the treatment compliance of diabetic patients.
Dynamic communities formation through semantic tags

Taggers in social tagging systems have the main role in giving identities to the objects. Tagged objects also represent perception of their taggers about them and can define identities of their taggers in return. Consequently, identities that are assigned to the objects and taggers have effect on the quality of their categorization and communities formation around them. Tags in social semantic tagging systems have formal definitions because they are mapped to the concepts that are defined in ontologies. Semantic tags are not only able to improve quality of tag assignments by solving some common tags ambiguity problems related to classic folksonomy systems (i.e., in particular polysemy and synonymy), but also to provide some meta data on top of the social relations based on contribution of taggers around semantic tags. Those meta data may be exploited to form dynamic communities which addresses the problems of lack of commonly agreed and evolving meaning of tags in social semantic tagging systems. This paper proposes an approach to form dynamic communities of related taggers around the tagged objects. Because our perceptions in each specific area of knowledge is evolving over time, the goal of our approach is also to evolve the represented knowledge in semantic tagging systems dynamically according to the latest perception of the related users.
Four year experience with the AO Anterior Thoracolumbar Locking Plate

For decades spinal surgeons have attempted to design simple, single stage anterior internal fixation systems for the thoracic and lumbar spine. Early devices presented both biomechanical and technical problems. The AO Anterior Thoracolumbar Locking Plate (ATLP) was designed to solve some of the problems encountered with early anterior instrumentation. The ATLP system is constructed in Commercially Pure titanium. It is a low profile device indicated for use for unstable burst fractures in the anterior column; metastatic tumor management; and degenerative diseases of the thoracolumbar spine between levels T10 and L5. Implantation of the device involves direct anterior decompression with sagittal reduction and corpectomy. This is followed by grafting reconstruction, and plate fixation. This device has been implanted in 25 patients with an average follow-up of 38 months. There were five (5) broken screws in three (3) patients, and no broken plates. Implant related postoperative complications included two misplaced screws. Preliminary results indicate that the ATLP system seems to be a safe, low profile, MRI/CT compatible device that provides definitive single stage fixation of the anterior spinal column.
Immune response of healthy horses to DNA constructs formulated with a cationic lipid transfection reagent

Deoxyribonucleic acid (DNA) vaccines are used for experimental immunotherapy of equine melanoma. The injection of complexed linear DNA encoding interleukin (IL)-12/IL-18 induced partial tumour remission in a clinical study including 27 grey horses. To date, the detailed mechanism of the anti-tumour effect of this treatment is unknown.



In the present study, the clinical and cellular responses of 24 healthy horses were monitored over 72 h after simultaneous intradermal and intramuscular application of equine IL-12/IL-18 DNA (complexed with a transfection reagent) or comparative substances (transfection reagent only, nonsense DNA, nonsense DNA depleted of CG). Although the strongest effect was observed in horses treated with expressing DNA, horses in all groups treated with DNA showed systemic responses. In these horses treated with DNA, rectal temperatures were elevated after treatment and serum amyloid A increased. Total leukocyte and neutrophil counts increased, while lymphocyte numbers decreased. The secretion of tumour necrosis factor alpha (TNFα) and interferon gamma (IFNγ) from peripheral mononuclear blood cells ex vivo increased after treatments with DNA, while IL-10 secretion decreased. Horses treated with DNA had significantly higher myeloid cell numbers and chemokine (C-X-C motif) ligand (CXCL)-10 expression in skin samples at the intradermal injection sites compared to horses treated with transfection reagent only, suggesting an inflammatory response to DNA treatment. In horses treated with expressing DNA, however, local CXCL-10 expression was highest and immunohistochemistry revealed more intradermal IL-12-positive cells when compared to the other treatment groups. In contrast to non-grey horses, grey horses showed fewer effects of DNA treatments on blood lymphocyte counts, TNFα secretion and myeloid cell infiltration in the dermis.



Treatment with complexed linear DNA constructs induced an inflammatory response independent of the coding sequence and of CG motif content. Expressing IL-12/IL-18 DNA locally induces expression of the downstream mediator CXCL-10. The grey horses included appeared to display an attenuated immune response to DNA treatment, although grey horses bearing melanoma responded to this treatment with moderate tumour remission in a preceding study. Whether the different immunological reactivity compared to other horses may contributes to the melanoma susceptibility of grey horses remains to be elucidated.
An Object-Oriented Approach to Switching Circuit Minimization

The determination of a minimal function to realize a specified set of outputs is e basic problem of switching circuit design. Circuit production costs have evidenced a steady decline over the past few years due mainly to technological advances in the areas of silicon compilation and VLSI implementation. In a just a few years, cost factors have taken a backseat to implmentation issues. Nonetheless, basic minimization techniques at the design [eve[, are still a major vehicle for cost containment. Techniques for the minimization of switching networks by Boolean reduction, Tabular methods, and Kar-naugh Maps are welt established. Such techniques can be easily implemented in conventional programming languages. Algorithmic implementations of such techniques, however, tend to be rather specialized and lacking in generality. In this paper we shall examine an object oriented approach to the circuit minimization problem. It wilt be demonstrated that an object representation of a circuit specification, forms the basis for an Expert System with the capability for both simulation and design. The procedures described in this paper were developed for a Personal Computer using PROLOG-2 (Expert Systems International). PROLOG was chosen for two reasons. First, the goat was to develop a set of procedures which would implement the symbolic minimization of a set of circuit object representations. PROLOG provides intrinsic facilities for the representation of objects as unit clauses. Further, since PROLOG is a ru[ e-based language by nature, Boolean minimization theorems are easi[y represented by PROLOG rules. Having specified the theorems as rules, the simplification is performed automatically by the PROLOG proof mechanism. Specifyin 9 Circuit Requirements A minimum specification for a circuit is a set of outputs under at t possible input conditions. Such a specification can be represented as a list. A simple combinatorial function of n inputs can have 2 n possible outputs. The output specification is a canonical list, the order of terms being the value of the minterm or maxterm. As an example consider the function f(A,B) = A + B. There are four possible input conditions represented by 00, 01, 10, and 11. The output list corresponding to these conditions (assuming a bootean value of "I" for true and "0" for false) is as follows: Permission to copy without fee all or part of this material is granted provided that the copies are not made or distributed for direct commercial advantage, the ACM copyright notice and the title of the …
Coin rotation task: a valid test for manual dexterity in multiple sclerosis.

Impaired manual dexterity is frequent and disabling in people with multiple sclerosis (MS). Therefore, convenient, quick, and validated tests for manual dexterity in people with MS are needed.



The aim of this study was to validate the Coin Rotation Task (CRT) for examining manual dexterity in people with MS.



This was a cross-sectional study.



A total of 101 outpatients with MS were assessed with the CRT, the Expanded Disability Status Scale (EDSS), the Scale for the Assessment and Rating of Ataxia (SARA), and the Modified Ashworth Scale (MAS); muscle strength and sensory deficits of the hands were noted. The concurrent validity and diagnostic accuracy of the CRT were determined by comparison with the 9-Hole Peg Test (9HPT). Construct validity was determined by comparison with a valid dexterity questionnaire. Multiple regression analyses were done to explore correlations of the CRT with the EDSS, SARA, MAS, muscle strength, and sensory deficits.



The CRT correlated significantly with the 9HPT (r=.73, P<.0001), indicating good concurrent validity. The cutoff values for the CRT relative to the 9HPT were 18.75 seconds for the dominant hand (sensitivity=81.5%, specificity=80.0%) and 19.25 seconds for the nondominant hand (sensitivity=90.3%, specificity=81.8%); these values indicated good diagnostic accuracy. Furthermore, the CRT correlated significantly with the dexterity questionnaire (r=-.49, P<.0001), indicating moderate construct validity. Multiple regression analyses revealed that the EDSS was the strongest predictor for impaired dexterity.



Most of the people examined had relapsing-remitting MS and EDSS scores of up to 7.



This study validated the CRT as a test that can be used easily and quickly to evaluate manual dexterity in people with MS.
Ocular toxicity in low-dose tamoxifen: A prospective study

To look at the incidence, symptomatology, course and reversibility of low-dose tamoxifen ocular toxicity. Sixty-five women with breast cancer, on tamoxifen oral therapy (20 mg/day), and a totally normal eye examination, were prospectively followed up. A full ophthalmic evaluation was done every 6 months, for a median of 30 months (range 4-79 months). Any sign of toxicity in the cornea, lens, retina or optic nerve was looked for, whether associated with a change in visual acuity or not. Ocular toxicity was documented in 8 patients, giving an incidence of 12%. Seven patients had keratopathy in the form of subepithelial deposits, whorls and linear opacities. Three of these patients had a concurrent symptomatic bilateral pigmentary retinopathy that warranted discontinuation of therapy. One patient developed bilateral optic neuritis that left her with optic nerve pallor and a decrease in vision. The patients who had the toxicity had a significantly higher tamoxifen cumulative dose (p = 0.03), and were longer on treatment (p = 0.04), than the non-affected ones. The keratopathy changes were reversible upon discontinuation of the drug. Prompt reporting of symptoms and yearly ophthalmic examinations are mandatory in patients on tamoxifen to detect toxic effects while these are still reversible.
Effect of HSV-2 serostatus on acquisition of HIV by young men: results of a longitudinal study in Orange Farm, South Africa.

The objectives of this study were to assess the impact among young men of herpes simplex virus type 2 (HSV-2) status on the acquisition of human immunodeficiency virus (HIV) and on the protective effect of male circumcision against HIV acquisition.



We used data collected during a male circumcision trial conducted in Orange Farm, South Africa. We estimated adjusted incidence rate ratios (IRRs) for HIV acquisition, using survival analysis and background characteristics, HSV-2 status, male circumcision status, and sexual behavior as covariates.



Compared with subjects who remained HSV-2 negative throughout the study, subjects who were HSV-2 positive at enrollment had an adjusted IRR of 3.3 (95% confidence interval [CI], 1.5-7.4; P=.004), and those who became HSV-2 positive during follow-up had an adjusted IRR of 7.0 (95% CI, 3.9-12.4; P<.001). The population fraction of incident HIV infection attributable to HSV-2 was 27.8% (95% CI, 17.7%-37.2%). Intention-to-treat analysis of the protective effect of male circumcision on HIV acquisition was the same among men with and men without HSV-2 (0.38 vs. 0.37; P=.93).



This study shows that HSV-2 has a substantial impact on HIV acquisition among young South African men. It suggests that HSV-2 infection enhances HIV acquisition and is responsible for approximately 25% of incident cases of HIV infection. However, the protective effect of male circumcision against HIV acquisition appears independent of HSV-2 serostatus.
Pravastatin inhibits cellular cholesterol synthesis and increases low density lipoprotein receptor activity in macrophages: in vitro and in vivo studies.

1. Pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) inhibitor, is a highly selective inhibitor of hepatic cholesterol synthesis. We studied the in vivo and in vitro effects of pravastatin on macrophage cholesterol metabolism. 2. The effects of incubating pravastatin with human monocyte derived macrophages (HMDM), mouse peritoneal macrophages (MPM) and a J-774 A.1 macrophage-like cell line, on macrophage cholesterol synthesis, cellular degradation of native low density lipoprotein (LDL) and modified LDL, cholesterol efflux from these cells and the cholesterol esterification rate were determined. 3. Pravastatin was administered either as one 40 mg dose or 40 mg daily for 8 weeks to normocholesterolaemic and hypercholesterolaemic individuals. The effects on cholesterol synthesis and degradation in monocytes derived from these subjects were studied. 4. In vitro, pravastatin resulted in a dose-dependent inhibition of macrophage cholesterol synthesis. Cellular degradation of native LDL increased by 119% in the presence of 0.1 mg ml-1 pravastatin. Degradation of both acetyl LDL and oxidized LDL was unaffected. Small concentrations of pravastatin (up to 0.19 micrograms ml-1) increased the cellular cholesterol esterification rate after incubation with LDL, but higher concentrations resulted in an inhibition of the esterification. 5. Single dose pravastatin administration caused a reduction in cholesterol synthesis by the subjects own HMDM by 62% and 47% in normocholesterolaemic and hypercholesterolaemic individuals, respectively. Chronic administration resulted in a 55% inhibition of cholesterol synthesis and a 57% increase in LDL degradation. 6. The results indicate that the selective uptake of pravastatin shown for hepatocytes can be extended to macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)
Development and validation of the Current Opioid Misuse Measure

Clinicians recognize the importance of monitoring aberrant medication-related behaviors of chronic pain patients while being prescribed opioid therapy. The purpose of this study was to develop and validate the Current Opioid Misuse Measure (COMM) for those pain patients already on long-term opioid therapy. An initial pool of 177 items was developed with input from 26 pain management and addiction specialists. Concept mapping identified six primary concepts underlying medication misuse, which were used to develop an initial item pool. Twenty-two pain and addiction specialists rated the items on importance and relevance, resulting in selection of a 40-item alpha COMM. Final item selection was based on empirical evaluation of items with patients taking opioids for chronic, noncancer pain (N=227). One-week test-retest reliability was examined with 55 participants. All participants were administered the alpha version of the COMM, the Prescription Drug Use Questionnaire (PDUQ) interview, and submitted a urine sample for toxicology screening. Physician ratings of patient aberrant behaviors were also obtained. Of the 40 items, 17 items appeared to adequately measure aberrant behavior, demonstrating excellent internal consistency and test-retest reliability. Cutoff scores were examined using ROC curve analysis and reasonable sensitivity and specificity were established. To evaluate the COMM's ability to capture change in patient status, it was tested on a subset of patients (N=86) that were followed and reassessed three months later. The COMM was found to have promise as a brief, self-report measure of current aberrant drug-related behavior. Further cross-validation and replication of these preliminary results is pending.
Long-term outcome of primary angioplasty compared with fibrinolysis across age groups: a Danish Multicenter Randomized Study on Fibrinolytic Therapy Versus Acute Coronary Angioplasty in Acute Myocardial Infarction (DANAMI-2) substudy.

Primary angioplasty in patients with acute ST-elevation myocardial infarction has been shown to be superior to fibrinolysis. Whether elderly patients have the same long-term benefit from angioplasty, compared with fibrinolysis, as younger patients is unknown.



The effect of angioplasty versus fibrinolysis was investigated in 1,572 patients from the DANAMI-2 study across age groups. End points were total mortality and a composite end point of death, reinfarction, or disabling stroke. Follow-up was 3 years.



Increasing age was associated with mortality (adjusted hazard ratio [HR] 2.45 per 10 year increment, 95% confidence interval [CI] 1.78-3.37, P < .0001) and a higher composite event rate (adjusted HR 1.51, CI 1.26-1.82, P < .0001). The long-term superiority of angioplasty over fibrinolysis on the combined outcome was independent of age: patients aged <56 years (HR 0.73, CI 0.41-1.31); 56 to 65 years (HR 0.83, CI 0.52-1.33); 66 to 75 years (HR 0.71, CI 0.48-1.04); and >75 years (HR 0.83, CI 0.59-1.17) (P = .006 for overall treatment effect and P = .5 for interaction between age and treatment). There was no long-term effect of angioplasty versus fibrinolysis on mortality and no interaction with age (P = .5 and P for interaction = .6).



The long-term effect of primary angioplasty compared with fibrinolysis in patients with ST-elevation myocardial infarction is not affected by age.
Impact of Toceranib/Piroxicam/Cyclophosphamide Maintenance Therapy on Outcome of Dogs with Appendicular Osteosarcoma following Amputation and Carboplatin Chemotherapy: A Multi-Institutional Study

We hypothesized that the addition of toceranib to metronomic cyclophosphamide/piroxicam therapy would significantly improve disease-free interval (DFI) and overall survival (OS) in dogs with appendicular osteosarcoma (OSA) following amputation and carboplatin chemotherapy.



This was a randomized, prospective clinical trial in which dogs with OSA free of gross metastatic disease (n = 126) received carboplatin chemotherapy (4 doses) following amputation. On study entry, dogs were randomized to receive piroxicam/cyclophosphamide with or without toceranib (n = 63 each) after completing chemotherapy. Patient demographics were not significantly different between both groups. During or immediately following carboplatin chemotherapy, 32 dogs (n = 13 toceranib; n = 19 control) developed metastatic disease, and 13 dogs left the study due to other medical conditions or owner preference. Following carboplatin chemotherapy, 81 dogs (n = 46 toceranib; n = 35 control) received the metronomic treatment; 35 dogs (n = 20 toceranib; n = 15 control) developed metastatic disease during the maintenance therapy, and 26 dogs left the study due to other medical conditions or owner preference. Nine toceranib-treated and 11 control dogs completed the study without evidence of metastatic disease 1-year following amputation. Toceranib-treated dogs experienced more episodes of diarrhea, neutropenia and weight loss than control dogs, although these toxicities were low-grade and typically resolved with supportive care. More toceranib-treated dogs (n = 8) were removed from the study for therapy-associated adverse events compared to control dogs (n = 1). The median DFI for control and toceranib treated dogs was 215 and 233 days, respectively (p = 0.274); the median OS for control and toceranib treated dogs was 242 and 318 days, respectively (p = 0.08). The one year survival rate for control dogs was 35% compared to 38% for dogs receiving toceranib.



The addition of toceranib to metronomic piroxicam/cyclophosphamide therapy following amputation and carboplatin chemotherapy did not improve median DFI, OS or the 1-year survival rate in dogs with OSA.