nils-herrmann/clean_scirepeval huggingface dataset:
A Graph Theoretic Approach to the Verification of Program Structures

For large computer programs, verification of compliance with structured programming rules can present difficult problems for programmers and managers. In order to certify that code is structured, an algorithm and test tool were recently developed to audit source code and verify the use of structured constructs. The paper describes the segmentation of programs as a way of representing their logical control structure; presents the basic algorithm, illustrates algorithm extensions; and briefly reports on experience in using the tool on a large software project.
Development of musculoskeletal toxicity without clear benefit after administration of PG-116800, a matrix metalloproteinase inhibitor, to patients with knee osteoarthritis: a randomized, 12-month, double-blind, placebo-controlled study

We performed a randomized, double-blind, placebo-controlled, multicenter, parallel-group, dose-response study of the efficacy and safety of the oral administration of PG-116800, a matrix metalloproteinase (MMP) inhibitor, in patients with mild to moderate knee osteoarthritis. The primary efficacy endpoints included the progression of joint space narrowing in the osteoarthritic knee, as measured by microfocal radiography with fluoroscopic positioning, and the reduction of symptoms (pain and stiffness) and/or the improvement of function, as measured by the Western Ontario and McMaster Universities osteoarthritis index (WOMAC). Four hundred and one patients were randomly assigned to either placebo (n = 80) or one of fourdoses of PG-116800: 25 mg (n = 81), 50 mg (n = 80), 100 mg (n = 80), or 200 mg (n = 80) taken twice daily for 12 months. During the study, the 200-mg dose was discontinued based on an increased frequency of musculoskeletal adverse effects. After 1 year of treatment, no statistically significant difference was observed between placebo and PG-116800 with regard to mean changes in minimum joint space width of the knee or to WOMAC scores. The most frequent adverse effect was arthralgia (35%). Twenty-three percent of evaluable patients had at least a 30% decrease from baseline of at least onerange-of-motion measurement of either shoulder at a follow-up visit. The percentage of patients with reduction in range of motion was significantly greater in the twohighest dose groups relative to placebo. Thirteen percent of patients, half of whom were in the 200-mg group, reported hand adverse events (oedema, palmar fibrosis, Dupuytren contracture, or persistent tendon thickness or nodules). The threemost frequent shoulder adverse events were reversible arthralgia, stiffness, and myalgia, which mostly affected the twohighest dose groups. The unfavorable risk-benefit balance of the MMP inhibitor PG-116800 in patients with knee osteoarthritis precludes further development of the compound for this indication. This study adds to the weight of evidence suggesting that side effect profiles of MMP inhibitors in general make them unsuitable for use in osteoarthritis.
Pharmacodynamic effects of high dose lovastatin in subjects with advanced malignancies

Lovastatin, an inhibitor of the rate-limiting enzyme in the cholesterol biosynthetic pathway, hydroxymethylglutaryl coenzyme A reductase, has shown interesting antiproliferative activities in cell culture and in animal models of cancer. The goal of the current study is to determine whether lovastatin bioactivity levels, in a range equivalent to those used in in vitro and preclinical studies, can be safely achieved in human subjects. Here we present the findings from a dose-escalating trial of lovastatin in subjects with advanced malignancies. Lovastatin was administered every 6 h for 96 h in 4-week cycles in doses ranging from 10 mg/m2 to 415 mg/m2. Peak plasma lovastatin bioactivity levels of 0.06–12.3 μM were achieved in a dose-independent manner. Cholesterol levels decreased during treatment and normalized during the rest period. A dose-limiting toxicity was not reached and there were no clinically significant increases in creatine phosphokinase or serum hepatic aminotransferases levels. No antitumor responses were observed. These results demonstrate that high doses of lovastatin, given every 4 h for 96 h, are well-tolerated and in select cases, bioactivity levels in the range necessary for antiproliferative activity were achieved.
Histamine-2 Receptor Antagonist Cannot Prevent Recurrent Peptic Ulcers in Patients With Atherosclerotic Diseases Who Receive Platelet ADP Receptor Antagonist Monotherapy: A Randomized-Controlled, Double-Blind, and Double-Dummy Trial

Proton pump inhibitor can effectively prevent recurrent peptic ulcers among atherosclerotic patients receiving clopidogrel monotherapy. However, the interaction between proton pump inhibitors and clopidogrel has raised concerns over the safety of combined use of the two medicines in clinical practice. The aims of this randomized-controlled, double-blind and double-dummy trial were to investigate the efficacy of histamine-2 receptor antagonist (H2RA) in the prevention of recurrent peptic ulcer in patients undergoing thienopyridine monotherapy.From January 2012 to 2016, long-termed thienopyridine users with a peptic ulcer history who did not have peptic ulcers at initial endoscopy were randomly assigned to receive either famotidine (40 mg, before bedtime) or placebo (before bedtime) for 6 months. Follow-up endoscopy was performed at the end of the 6th month and whenever dyspepsia, hematemesis, or melena occurred.The cumulative incidence of recurrent peptic ulcer during the 6-month period was 7.0% in famotidine group (n=114) and 11.4% in the placebo group (n=114). The two patient groups had comparable cumulative incidence of peptic ulcer (difference, 4.4%; 95% confidence interval (CI), −11.7 to 2.9%; P=0.239). Additionally, there was no difference in the cumulative incidence of ulcer bleeding (2.6% vs. 1.8%; difference, 0.8%; 95% CI, −0.6 to 2.4%, P=1.000) between famotidine and placebo groups. However, the former had a lower incidence of gastroduodenal erosion than the latter (21.1% vs. 36.8%; difference, 15.7%; 95% CI, −27.3 to −4.1%; P=0.013).CONCLUSIONS:Famotidine cannot decrease the incidence of peptic ulcer or ulcer bleeding in thienopyridine users with atherosclerotic disease and a history of peptic ulcer.
Physician-pharmacist collaborative care in dyslipidemia management: the perception of clinicians and patients.

Collaborative practices allow physicians and pharmacists to comanage pharmacotherapy to maximize the benefits of medication regimens. The Trial to Evaluate an Ambulatory primary care Management program for patients with dyslipidemia (TEAM) study compared the efficacy of a physician-pharmacist collaborative primary care (PPCC) intervention, where pharmacists requested laboratory tests and adjusted medication dosage, to the usual care (UC) for patients under treatment with lipid-lowering medication.



In a qualitative study nested within the TEAM study, the perceptions of physicians, pharmacists, and patients regarding the PPCC model, interprofessional collaboration, and the clinicians' willingness to implement the model in their practice were explored.



In the area of Montreal (Quebec, Canada), TEAM study participants assigned to the PPCC group were invited to participate. Individual semistructured interviews with physicians (n=7) and 2 six-member focus groups with pharmacists (n=12) and patients (n=12) were analyzed using a phenomenological approach.



The vast majority of participants reported PPCC was more structured and systematic than the UC they had received previously, wherein physicians prescribe and adjust pharmacotherapy and pharmacists provide the counseling and dispense medications. Many patients felt they received better follow-up and reported being reassured and well informed, making them more inclined to care for themselves better. These feelings were attributed largely to the pharmacists' accessibility and ability to communicate with them easily. Given the physician shortage, physicians perceived interprofessional collaboration as almost inevitable. They considered PPCC to be safe and effective. However, obstacles were also identified. Physicians were concerned that it might alter their special relationship with patients and threaten their overall medical follow-up. Pharmacists felt enthusiastic about their new role, but found PPCC time consuming and thought it might not be applicable to all the patients.



PPCC model was highly appreciated by patients, and clinicians saw it as beneficial to patients. However, several obstacles still have to be overcome before the model can be implemented in the current health care context.
MAGENTA technology: multi-agent systems for industrial logistics

We introduce MAGENTA'S commercial multi-agent systems technology, and illustrate its practical use by describing a field-tested application in the area of logistics/scheduling. MAGENTA technology provides two integrated toolsets for building industrial-strength systems: the Ontology Management Toolkit (which enables designers to capture the concepts and interrelationships between concepts in an application), and the Virtual Marketplace Engine (the platform supporting agent interaction in MAGENTA'S technology); in addition, run-time visualisation and monitoring tools are provided for debugging systems. The application we describe is a field-tested scheduling/logistics system for Tankers International, which provides intelligent support in the scheduling of a 46-strong Very Large Crude Carrier (VLCC) fleet.
Prospective study establishing a management plan for impacted third molar in patients undergoing hematopoietic stem cell transplantation.

Although dental treatment before hematopoietic stem cell transplantation (HSCT) is essential to prevent serious infections from oral sources, the best management plan for impacted third molar (ITM) is unclear.



This study was planned to establish a management plan for ITM. Eighty-four candidates for HSCT therapy were consecutively enrolled in the prospective trial. The management plan, which was evidence based and prospectively decided, was to extract the symptomatic ITMs and to leave the asymptomatic ones untreated, regardless of their impacted position.



Eighty-seven ITMs were observed in 35 patients. The ITMs were in the maxilla of 25 patients and the mandible of 28 patients. Dental extraction of 7 teeth was performed in 6 patients without complications. All of the patients received the scheduled HSCT therapy and none experienced odontogenic infection while myelosuppressed.



This management plan for ITM appears to be appropriate for pre-HSCT patients. Moreover, the experienced dental provider is suggested as a necessary and valuable part of the HSCT team.
Results of a Community-Based Low-Literacy Nutrition Education Program

A nutrition intervention focused on low-fat eating pattern changes was conducted among low-literacy participants in a Twin Cities Metropolitan area Expanded Food and Nutrition Education Program (EFNEP). A total of 134 EFNEP participants who participated in the intervention were compared to 70 comparison participants who received EFNEP nutrition education materials. Associations between changes in outcome variables specific to the intervention were evaluated using mixed-model regression analyses. The principal effects seen for this program were related to changes in eating pattern scales. More modest effects were seen in scales related to attitudes of low-fat eating, and although changes in dietary fat intake as measured by 24-hour dietary interviews suggested a positive intervention effect, this did not approach statistical significance.
Correlation of pulsatility index with intracranial pressure in traumatic brain injury.

In traumatic brain injury (TBI) patients, it is desired to monitor the intracranial pressure (ICP) to assess the cerebral haemodynamics and guide the therapy. The study was designed to see if the pulsatility index (PI) measured by transcranial Doppler ultrasonography (TCD) predicts information about ICP values.



In 52 TBI patients with Glasgow Coma Scale (GCS) score < 9, invasive intracranial monitoring and TCD ultrasonography for PI were performed through five days. ICP, cerebral perfusion pressure (CPP), PI values were recorded and calculated. The correlation and regression analysis between ICP, PI and CPP were investigated in the whole group and in patients with a Glasgow Outcome Score (GOS) of 3-5.



The decline in ICP and PI values was significant through five days. The correlation between ICP and PI was strongly significant (p < 0.0001) on days 1, 3 and 5. In patients with a GOS of 3-5, correlation of ICP and PI was also observed. The only significant correlation observed between CPP and PI was on day 5.



The strong correlation observed between ICP and PI through the management period of TBI patients can lead us to use TCD ultrasonography-derived PI as a guide if invasive monitoring is not available.
All-trans retinoic acid as adjunct to intensive treatment in younger adult patients with acute myeloid leukemia: results of the randomized AMLSG 07-04 study

The aim of this clinical trial was to evaluate the impact of all-trans retinoic acid (ATRA) in combination with chemotherapy and to assess the NPM1 status as biomarker for ATRA therapy in younger adult patients (18–60 years) with acute myeloid leukemia (AML). Patients were randomized for intensive chemotherapy with or without open-label ATRA (45 mg/m2, days 6–8; 15 mg/m2, days 9–21). Two cycles of induction therapy were followed by risk-adapted consolidation with high-dose cytarabine or allogeneic hematopoietic cell transplantation. Due to the open label character of the study, analysis was performed on an intention-to-treat (ITT) and a per-protocol (PP) basis. One thousand one hundred patients were randomized (556, STANDARD; 544, ATRA) with 38 patients treated vice versa. Median follow-up for survival was 5.2 years. ITT analyses revealed no difference between ATRA and STANDARD for the total cohort and for the subset of NPM1-mutated AML with respect to event-free (EFS; p = 0.93, p = 0.17) and overall survival (OS; p = 0.24 and p = 0.32, respectively). Pre-specified PP analyses revealed better EFS in NPM1-mutated AML (p = 0.05) and better OS in the total cohort (p = 0.03). Explorative subgroup analyses on an ITT basis revealed better OS (p = 0.05) in ATRA for genetic low-risk patients according to ELN recommendations. The clinical trial is registered at clinicaltrialsregister.eu (EudraCT Number: 2004-004321-95).
Do empowered stroke patients perform better at self-management and functional recovery after a stroke? A randomized controlled trial

Self-management after a stroke is a challenge because of multifaceted care needs and complex disabling consequences that cause further hindrance to patient participation. A 13-week stroke patient empowerment intervention (Health Empowerment Intervention for Stroke Self-management [HEISS]) was developed to enhance patients' ability to participate in self-management.



To examine the effects of the empowerment intervention on stroke patients' self-efficacy, self-management behavior, and functional recovery.



This is a single-blind randomized controlled trial with stroke survivors assigned to either a control group (CG) receiving usual ambulatory rehabilitation care or the HEISS in addition to usual care (intervention group [IG]). Outcome data were collected at baseline (T0), 1 week (T1), 3 months (T2), and 6 months (T3) postintervention. Data were analyzed on the intention-to-treat principle. The generalized estimating equation model was used to assess the differential change of self-efficacy in illness management, self-management behaviors (cognitive symptom management, communication with physician, medication adherence, and self-blood pressure monitoring), and functional recovery (Barthel and Lawton indices) across time points (baseline = T0, 1 week = T1, 3 months = T2, and 6 months = T3 postintervention) between the two groups.



A total of 210 (CG =105, IG =105) Hong Kong Chinese stroke survivors (mean age =69 years, 49% women, 72% ischemic stroke, 89% hemiparesis, and 63% tactile sensory deficit) were enrolled in the study. Those in IG reported better self-efficacy in illness management 3-month (P=0.011) and 6-month (P=0.012) postintervention, along with better self-management behaviors at all follow-up time points (all P<0.05), apart from medication adherence (P>0.05). Those in IG had significantly better functional recovery (Barthel, all P<0.05; Lawton, all P<0.001), compared to CG. The overall dropout rate was 16.7%.



Patient empowerment intervention (HEISS) may influence self-efficacy in illness management and improve self-management behavior and functional recovery of stroke survivors. Furthermore, the HEISS can be conducted in parallel with existing ambulatory stroke rehabilitation services and provide added value in sustaining stroke self-management and functional improvement in the long term.
Contribution of ribavirin transporter gene polymorphism to treatment response in peginterferon plus ribavirin therapy for HCV genotype 1b patients.

Standard-dose ribavirin is crucial for the standard-of-care treatment of chronic hepatitis C virus (HCV) infection. Equilibrative nucleoside transporter 1 (ENT1), encoded by SLC29A1 gene, is the main transporter that imports ribavirin into human hepatocytes.



To determine whether single nucleotide polymorphisms (SNPs) at the SLC29A1 gene could influence the probability of treatment response compared with other baseline and host genetic factors.



A total of 526 East Asian patients monoinfected with HCV genotype 1b who had received pegylated interferon alpha plus ribavirin therapy were enrolled in this study. They were assigned randomly to the derivation and confirmatory groups. SNPs related to the IL28B, ITPA and SLC29A1 genes were genotyped using real-time detection polymerase chain reaction. Factors associated with sustained virological response (SVR) were analysed using multiple logistic regression analysis.



Multivariate analysis for the derivation group identified six baseline variables significantly and independently associated with SVR: age [P = 0.023, odds ratio (OR) = 0.97], gender (P = 0.0047, OR = 2.25), platelet count (P = 0.00017, OR = 1.11), viral load (P = 0.00026, OR = 0.54), IL28B SNP rs12979860 (P = 1.09 × 10(-7) , OR = 8.68) and SLC29A1 SNP rs6932345 (P = 0.030, OR = 1.85). Using the model constructed by these independent variables, positive and negative predictive values and predictive accuracy were 73.3, 70.1 and 71.9% respectively. For the confirmatory group, they were 71.4, 84.6 and 75.3% respectively. The SLC29A1 and IL28B SNPs were also significantly associated with rapid virological response.



The SNP at the major ribavirin transporter ENT1 gene SLC29A1 was one of significantly independent factors influencing treatment response, although the impact on the prediction was small.
Tonabersat, a gap-junction modulator: efficacy and safety in two randomized, placebo-controlled, dose-ranging studies of acute migraine.

Tonabersat is a novel benzopyran derivative that blocks the cortical spreading depression proposed to be associated with migraine attacks. The ability of single oral doses of 15, 25, 40 and 80 mg of tonabersat to relieve the symptoms of moderate to severe migraine was evaluated in 859 migraineurs enrolled in two dose-ranging, double-blind, randomized, placebo-controlled, parallel-group trials, one international and the other North American. In the international study, significantly more patients given tonabersat than given placebo experienced relief of headache pain at 2 h (15 mg, 36.8%; 40 mg, 40.7%), the principal efficacy variable, and at 4 h (40 mg, 63.0%) and complete abolition of headache at 4 h (40 mg, 34.3%). None of the primary or secondary efficacy variables indicated significant differences between tonabersat and placebo in the North American study. Tonabersat was generally well tolerated, with dizziness and nausea the most common side-effects. Serious adverse events were uncommon, and no patient withdrew from either study because of adverse events. These results suggest a possible interplay between tonabersat pharmacokinetics (the relatively long time required to reach maximum plasma concentrations) and patient characteristics (previous triptan exposure) in the management of acute migraine attacks. Based on the pharmacokinetics and actions on cortical spreading depression, tonabersat may have potential value in migraine prophylaxis.
Thrombus Aspiration in Patients With ST-Segment Elevation Myocardial Infarction Presenting Late After Symptom Onset.

The aim of this study was to examine whether manual thrombus aspiration reduces microvascular obstruction assessed by cardiac magnetic resonance imaging in patients with ST-segment elevation myocardial infarction (STEMI) presenting late after symptom onset.



Thrombus aspiration is an established treatment option in patients with STEMI undergoing primary percutaneous coronary intervention (PCI). However, there are only limited data on the efficacy of thrombus aspiration in patients with STEMI presenting ≥12 h after symptom onset.



Patients with subacute STEMI presenting ≥12 and ≤48 h after symptom onset were randomized to primary PCI with or without manual thrombus aspiration in a 1:1 ratio. Patients underwent cardiac magnetic resonance imaging 1 to 4 days after randomization. The primary endpoint was the extent of microvascular obstruction.



A total of 152 patients underwent randomization. The mean time between symptom onset and PCI was 28 ± 12 h. Baseline characteristics were comparable between groups. The majority of patients (60%) showed at least a moderate amount of viable myocardium in the affected region. Extent of microvascular obstruction was not significantly different between patients assigned to thrombus aspiration and the control group (2.5 ± 4.0% vs. 3.1 ± 4.4% of left ventricular mass, p = 0.47). There were also no significant differences in infarct size, myocardial salvage, left ventricular ejection fraction, and angiographic and clinical endpoints between groups.



In this first randomized trial of thrombectomy in patients with STEMI presenting late after symptom onset, routine thrombus aspiration before PCI failed to show a benefit for markers of reperfusion success.