nils-herrmann/clean_scirepeval huggingface dataset:
Early virological failure in naive human immunodeficiency virus patients receiving saquinavir (soft gel capsule)-stavudine-zalcitabine (MIKADO trial) is not associated with mutations conferring viral resistance.

The MIKADO trial was designed to evaluate the efficacy of stavudine-zalcitabine-saquinavir (soft gel capsule) [d4T-ddC-SQV(SGC)] in 36 naive patients (-3.3 log(10) units at week 24 [W24]). Among the 29 patients remaining on d4T-ddC-SQV(SGC) until W24, 10 harbored a virological failure (viral load of >200 copies/ml at W24) (group 1). To determine the reasons for therapeutic failure, genotypic and phenotypic resistance test results and SQV concentrations in plasma were analyzed and compared to those in successfully treated patients (viral load of <200 copies/ml at W24) (group 2). Reverse transcriptase and protease genotypic analyses in group 1 revealed the acquisition of only one SQV-associated mutation (L90M) in only two patients. There was no significant increase in the 50 or 90% inhibitory concentration of SQV in patients with or without the L90M mutation. However, the fact that two patients developed an L90M mutation only 4 weeks after relapse points to the need for genotypic resistance testing in the context of an initial failure of the antiretroviral regimen. At W24, the median SQV concentration in group 1 (71 ng/ml) was significantly lower than in group 2 (475 ng/ml), and the plasma SQV concentration was correlated with the viral load at W24 (r = -0.5; P<0.05) and with the drop in viral load between day 0 and W24 (r = -0.5; P<0.01). These results and the fact that the plasma SQV concentrations in the two groups prior to relapse (W12) were not significantly different strongly suggest that the early failure of this combination is not due to viral resistance but to a lack of compliance, pharmacological variability, and drug interactions or a combination of these factors.
Leakage-resilient certificateless public key encryption

In certificateless public key encryption (CL-PKE), the Private Key Generator (PKG) keeps a master secret key to generate a partial private key corresponding to a user's identity. Together with a secret value generated by the user, a full private key can be constructed for decryption. Traditional security model for CL-PKE assumes that (i) both the master secret key of the PKG and the full private key of the user under attack are in absolute secrecy; and (ii) the attacker can only obtain either the target user's secret value without any partial knowledge of the partial private key or vice versa. However, the advancement of practical side-channel attacks enable attackers to obtain partial information of both keys easily, making the above assumption invalid.
 In this paper, we give the first leakage-resilient CL-PKE. We consider different leakage conditions for Type I (third party attackers) and Type II (honest-but-curious PKG) attackers, following the classification in traditional CL-PKE. We give a concrete construction in the composite order bilinear group. We prove the security of our scheme in the standard model, overcoming some technical difficulties in the security proofs for both Type I and Type II attackers of CL-PKE.
Parenteral antibiotic prophylaxis of bacterial infections does not improve cost-efficacy of oral norfloxacin in cirrhotic patients with gastrointestinal bleeding

Selective intestinal decontamination with norfloxacin is useful in the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding. However, bleeding cirrhotic patients with ascites, encephalopathy, or shock are at high risk to develop bacterial infections in spite of prophylactic norfloxacin. The aim of this study was to assess whether the addition of intravenous ceftriaxone could improve the efficacy of prophylaxis with norfloxacin in these patients.Fifty-six cirrhotic patients with gastrointestinal hemorrhage and ascites, encephalopathy, or shock were randomized into two groups: Group 1 (n = 28) received oral norfloxacin 400 mg/12 h for 7 days, and group 2 (n = 28) received norfloxacin plus intravenous ceftriaxone 2 g daily during the first 3 days of admission.Ten patients were excluded because of community-acquired infection, surgery, or death within the first 24 h. The incidence of bacterial infections during hospitalization was 18.1% in group 1 and 12.5% in group 2 (p= NS). The incidence of severe infections (spontaneous bacterial peritonitis, bacteremia, or pneumonia) was also similar in both groups: 9% in group 1 versus 8.3% in group 2 (p= NS). There were no statistical differences between the two groups with respect to duration of hospitalization or mortality. The cost of antibiotic therapy (including prophylaxis and treatment of infections) was significantly higher in group 2.Conclusions:These results suggest that the addition of intravenous ceftriaxone during the first 3 days of hospitalization does not improve the cost-efficacy of oral norfloxacin in the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding and high risk of infection.
Managing TCP Connections Under Persistent HTTP

traffic dominates Internet traffic. The exchange of HTTP messages is implemented using the connection-oriented TCP. HTTP=1.0 establishes a new TCP connection for each HTTP request, resulting in many consecutive short-lived TCP connections. The emerging HTTP=1.1 reduces latencies and overhead from closing and re-establishing connections by supporting persistent connections as a default. A TCP connection which is kept open and reused for the next HTTP request reduces overhead and latency. Open connections, however, consume sockets and memory for socket-buffers. This trade-off establishes a need for connection-management policies. We propose policies that exploit embedded information in the HTTP request messages, e.g., senders’ identities and requested URLs, and compare them to the fixed-timeout policy used in the current implementation of the Apache Web server. An experimental evaluation of connection management policies at Web servers, conducted using Web server logs, shows that our URL-based policy consistently outperforms other policies, and achieves significant 15–25% reduction in cost with respect to the fixed-timeout policy. Hence, allowing Web servers and clients to more fully reap the benefits of persistent HTTP.
End-of-dose deterioration in non ergolinic dopamine agonist monotherapy of Parkinson’s disease

The study was designed to investigate the possible occurrence of “wearing-off” (WO) during dopamine agonist (DA) monotherapy. Sixty patients with “de novo” idiopathic PD were randomised into one of two DA monotherapy branches to receive oral ropinirole at 15 mg per day, or pramipexole at 2.1 mg per day. DA doses could be increased in the following two years but levodopa could not be added until the study ended. WO was assessed by self-evaluation charts confirmed by a blinded observation of a 30% or greater deterioration in the Unified Parkinson’s Disease Rating Scale (UPDRS) motor score. Proc Mixed and Kaplan-Meier curves evaluated treatment variables as a function of time. T-tests were used to compare post-hoc variables reclassified according to WO occurrence. Thirty patients received ropinirole, and 30 pramipexole monotherapy. Eighteen patients (30%) experienced “wearing-off” 15–21 months after beginning monotherapy. No differences were observed between treatments. WO phenomena was observed 3.4 ± 0.3 hours after intake of the morning or afternoon dose and consisted of UPDRS score worsening by 11.1 ± 2.1 points (69–111% more than “on” score). Statistical evaluation gave evidence of differences between patients who experienced WO and those who did not: UPDRS motor scores obtained at admission to the study were higher (by 3.4 ± 0.2 points, p = 0.01 t-test) and DA doses at 6–12 months were higher in fluctuating patients. UPDRS motor scores deteriorated, however. similarly and there were no differences, in UPDRS scores recorded in ON conditions, between fluctuating and non-fluctuating patients at the end of the study. Our findings provide evidence of WO phenomena in patients with early PD receiving non-ergolinic DA monotherapy.
Visual and Textual Knowledge Representation in DESIRE

In this paper, graphical, conceptual graph-based representations for knowledge structures in the compositional development method DESIRE for knowledge-based and multi-agent systems are presented, together with a graphical editor based on the Constraint Graph environment. Moreover, a translator is described which translates these graphical representations to textual representations in DESIRE. The strength of the combined environment is a powerful -yet easy-to-use -framework to support the development of knowledge based nd multi-agent systems. Finally, a mapping is presented from DESIRE, that is based on order sorted predicate logic, to Conceptual Graphs.
Robust PCA and classification in biosciences

Principal components analysis (PCA) is a very popular dimension reduction technique that is widely used as a first step in the analysis of high-dimensional microarray data. However, the classical approach that is based on the mean and the sample covariance matrix of the data is very sensitive to outliers. Also, classification methods based on this covariance matrix do not give good results in the presence of outlying measurements.



First, we propose a robust PCA (ROBPCA) method for high-dimensional data. It combines projection-pursuit ideas with robust estimation of low-dimensional data. We also propose a diagnostic plot to display and classify the outliers. This ROBPCA method is applied to several bio-chemical datasets. In one example, we also apply a robust discriminant method on the scores obtained with ROBPCA. We show that this combination of robust methods leads to better classifications than classical PCA and quadratic discriminant analysis.


AVAILABILITY
All the programs are part of the Matlab Toolbox for Robust Calibration,
Efficacy and safety of canagliflozin over 52 weeks in patients with type 2 diabetes on background metformin and pioglitazone

The efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 inhibitor, was evaluated in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin and pioglitazone.



In this randomized, double-blind, phase 3 study, patients (N = 342) received canagliflozin 100 or 300 mg during a 26-week, placebo-controlled, core period and a 26-week, active-controlled extension in which placebo-treated patients were switched to sitagliptin 100 mg. Efficacy comparisons for canagliflozin versus placebo at week 26 are reported, with no comparisons versus sitagliptin at week 52 (sitagliptin used to maintain double-blind and control for safety). Safety data are reported for canagliflozin and placebo/sitagliptin.



Canagliflozin 100 and 300 mg significantly lowered haemoglobin A1c (HbA1c) compared with placebo at week 26 (-0.89%, -1.03% and -0.26%; p < 0.001); reductions with canagliflozin 100 and 300 mg were maintained at week 52 (-0.92% and -1.03%). Relative to placebo, both canagliflozin doses significantly reduced body weight (-2.5 and -3.5 kg), fasting plasma glucose and systolic blood pressure (BP) at week 26 (p < 0.05 for all), with reductions maintained at week 52. Overall adverse event (AE) incidence over 52 weeks was 69.9, 76.3 and 76.5% with canagliflozin 100 and 300 mg and placebo/sitagliptin; AE-related discontinuation and serious AE rates were low. Incidences of genital mycotic infections and AEs related to osmotic diuresis and volume depletion were higher with canagliflozin than placebo/sitagliptin.



Canagliflozin improved glycaemic control, reduced body weight and systolic BP, and was generally well tolerated in patients with T2DM on metformin and pioglitazone over 52 weeks.
18F-FDG PET predicts survival after pretargeted radioimmunotherapy in patients with progressive metastatic medullary thyroid carcinoma

PET is a powerful tool for assessing targeted therapy. Since 18F-FDG shows a potential prognostic value in medullary thyroid carcinoma (MTC), this study evaluated 18F-FDG PET alone and combined with morphological and biomarker evaluations as a surrogate marker of overall survival (OS) in patients with progressive metastatic MTC treated with pretargeted anti-CEA radioimmunotherapy (pRAIT) in a phase II clinical trial. Patients underwent PET associated with morphological imaging (CT and MRI) and biomarker evaluations, before and 3 and 6 months, and then every 6 months, after pRAIT for 36 months. A combined evaluation was performed using anatomic, metabolic and biomarker methods. The prognostic value of the PET response was compared with demographic parameters at inclusion including age, sex, RET mutation, time from initial diagnosis, calcitonin and CEA concentrations and doubling times (DT), SUVmax, location of disease and bone marrow involvement, and with response using RECIST, biomarker concentration variation, impact on DT, and combined methods. Enrolled in the study were 25 men and 17 women with disease progression. The median OS from pRAIT was 3.7 years (0.2 to 6.5 years) and from MTC diagnosis 10.9 years (1.7 to 31.5 years). After pRAIT, PET/CT showed 1 patient with a complete response, 4 with a partial response and 24 with disease stabilization. The combined evaluation showed 20 responses. For OS from pRAIT, univariate analysis showed the prognostic value of biomarker DT (P = 0.011) and SUVmax (P = 0.038) calculated before pRAIT and impact on DT (P = 0.034), RECIST (P = 0.009), PET (P = 0.009), and combined response (P = 0.004) measured after pRAIT. PET had the highest predictive value with the lowest Akaike information criterion (AIC 74.26) as compared to RECIST (AIC 78.06), biomarker variation (AIC 81.94) and impact on DT (AIC 79.22). No benefit was obtained by combining the methods (AIC 78.75). This result was confirmed by the analysis of OS from MTC diagnosis. 18F-FDG PET appeared as the most potent and simplest prognostic method to predict survival in patients with progressive MTC treated with pRAIT. Biomarker DT before pRAIT also appeared as an independent prognostic factor, but no benefit was found by adding morphological and biomarker evaluation to PET assessment.
Increased proinflammatory cytokines in patients with chronic stable angina and their reduction by aspirin.

Proinflammatory cytokines released by injured endothelium facilitate interaction of endothelial cells with circulating leukocytes and thus may contribute to development and progression of atherosclerosis. We investigated whether cytokines and C-reactive protein (CRP) are indicative of myocardial ischemia or of diseased vessels and whether they are influenced by aspirin treatment in patients with chronic stable angina.



Plasma macrophage colony stimulating factor (MCSF), IL-1b, IL-6, and CRP were measured in 60 stable patients after 48-hour Holter monitoring and in 24 matched controls. All patients had angiographic documentation of disease and positive exercise ECGs. Patients with ischemia on Holter monitoring (n=40) received aspirin or placebo in a 6-week, randomized, double blind, crossover trial. Blood sampling was repeated at the end of each treatment phase (3 weeks). Compared to controls, patients had more than twice median MCSF (800 versus 372 pg/mL), IL-6 (3.9 versus 1.7 pg/mL), and CRP (1.25 versus 0.23 mg/L) levels (P<0.01 for all comparisons). MCSF was related to ischemia on Holter monitoring (P<0.01), to low ischemic threshold during exercise (P<0.01), and together with IL-1b to number of diseased vessels (P<0.05). MCSF, IL-6, and CRP were all reduced after 6 weeks of aspirin treatment (P<0.05).



These findings suggest that cytokines are associated with both ischemia and anatomic extent of disease in patients with stable angina. Reduced cytokine and CRP levels by aspirin may explain part of aspirin's therapeutic action.
Inverse Association between Dietary Intake of Selected Carotenoids and Vitamin C and Risk of Lung Cancer

While diets rich in fruit and vegetables appear to reduce lung cancer risk, the evidence for individual carotenoid and vitamin intakes has been judged too limited to reach firm conclusions. Data from a case-control study of lung cancer (Montreal, QC, Canada, 1996-2002) were used to investigate the role of dietary intakes of β-carotene, α-carotene, β-cryptoxanthin, lutein/zeaxanthin, lycopene, and vitamin C in lung cancer risk. In-person interviews elicited dietary information from 1,105 incident cases and 1,449 population controls. Usual frequency of consumption of 49 fruits and vegetables 2 years prior to diagnosis/interview was collected. Odds ratios (ORs) and 95% confidence intervals (CIs) between intake variables and lung cancer were estimated using logistic or polytomous regression, adjusting for potential confounding factors including a detailed smoking history. ORs associated with upper versus lower tertiles of intake were 0.66 (95% CI = 0.51-0.84) for β-carotene, 0.70 (95% CI = 0.55-0.90) for α-carotene, 0.65 (95% CI = 0.51-0.84) for β-cryptoxanthin, 0.75 (95% CI = 0.59-0.95) for lycopene, and 0.74 (95% CI = 0.58-0.96) for vitamin C. ORs suggestive of a protective effect were found for elevated intakes of β-carotene, α-carotene, β-cryptoxanthin, and lycopene in male heavy smokers and of vitamin C in female heavy smokers. Selected antioxidants were also associated with a lower risk of lung cancer in female moderate smokers, and of squamous cell carcinoma, adenocarcinoma, and small cell carcinoma. These results suggest that several dietary antioxidants found in common food sources may protect against lung cancer, even among heavy smokers.
Genetic polymorphisms contribute to acute kidney injury after coronary artery bypass grafting.

Acute kidney injury is one of the most serious complications after cardiac surgery. Genetic polymorphisms are reported to be associated with postoperative renal impairment. The aim of this study was to investigate the relationship between selected gene polymorphisms and acute kidney injury after cardiac surgery.



Two hundred forty-eight elective coronary artery bypass grafting procedure patients were enrolled in the study. Angiotensin-converting enzyme (ACE) II, ID, and DD, apolipoprotein E (APO E), and angiotensin II type 1 receptor (AGTR1) A1166C genotypes were detected by polymerase chain reaction. Plasma levels of ACE were analyzed by enzyme-linked immunosorbent assay. Acute kidney injury after cardiac surgery was graded according to the RIFLE (risk, injury, failure, loss, and end-stage kidney disease) classification.



In our study, 21.8% of patients had acute renal impairment after cardiac surgery. Among the 54 patients with acute kidney injury, ACE D allele frequency was 0.620. The plasma levels of ACE were significantly higher in the D allele carriers (P = .018). Three of the 54 patients with acute kidney injury were APO E epsilon 4 allele carriers (P = .002). AGTR1 C allele carriers constituted 46% of all patients with postoperative acute kidney injury. There was no statistically significant difference between A allele homozygotes and C allele carriers with respect to postoperative renal dysfunction (P > .05).



The present findings support the hypothesis that ACE I/D and APO E gene polymorphisms may play a role in the development of acute kidney injury after cardiac surgery. However, AGTR1 does not have a unique association with postoperative renal impairment.
Anti-tumour necrosis factor agents reduce non-steroidal anti-inflammatory drug-induced small bowel injury in rheumatoid arthritis patients.

The role of tumour necrosis factor α (TNFα) in the pathogenesis of non-steroidal anti-inflammatory drug (NSAID)-induced small intestinal damage remains unclear. We evaluated the preventive effect of anti-TNF therapy against NSAID-induced enteropathy in rheumatoid arthritis (RA) patients.



Capsule endoscopy was performed in 95 consecutive RA patients who received NSAID for more than 3 months, with or without anti-TNF therapy over a period of 3 months. The findings were scored from 0 to 4: 0, normal; 1, red spots; 2, one to four erosions; 3, more than four erosions; and 4, large erosions/ulcers. The relationship between the use of anti-TNF therapy and the risk of severe damage (scores 3 or 4) or the most severe damage (score 4) was assessed using multiple logistic regression analysis. Furthermore, a propensity score matching analysis was performed to reduce the effects of TNF selection bias.



By stratifying the patients on the basis of anti-TNF therapy, we obtained crude OR of 0.23 for severe damage (95% CI 0.09 to 0.65) and 0.37 for the most severe damage (95% CI 0.16 to 0.86). This protective effect of anti-TNF therapy remained robust to adjustments for baseline characteristics, with the adjusted OR for severe damage and the most severe damage ranging from 0.23 to 0.26 and 0.06 to 0.41, respectively. Propensity score matching yielded similar results and showed the protective effects of anti-TNF therapy against severe and most severe damage.



Anti-TNF therapy may protect against NSAID-induced small intestinal damage in RA patients.
Application of artificial neural networks to the analysis of dynamic MR imaging features of the breast

The discriminative ability of established diagnostic criteria for MRI of the breast is assessed, and their relative relevance using artificial neural networks (ANNs) is determined. A total of 89 women with 105 histopathologically verified breast lesions (73 invasive cancers, 2 in situ cancers, and 30 benign lesions) were included in this study. A T1-weighted 3D FLASH sequence was acquired before and seven times after the intravenous administration of gadopentetate dimeglumine at a dose of 0.2 mmol/kg body weight. ANN models were built to test the discriminative ability of kinetic, morphologic, and combined MR features. The subjects were randomly divided into two parts: a training set of 59 lesions and a verification set of 46 lesions. The training set was used for learning, and the performance of each model was evaluated on the verification set by measuring the area under the ROC curve (A z ). An optimally minimized model was constructed using the most relevant input variables that were determined by the automatic relevance determination (ARD) method. ANN models were compared with the performance of a human reader. Margin type, time-to-peak enhancement, and washout ratio showed the highest discriminative ability among diagnostic criteria and comprised the minimized model. Compared with the expert radiologist (A z =0.799), using the same prediction scale, the minimized ANN model performed best (A z =0.771), followed by the best kinetic (A z =0.743), the maximized (A z =0.727), and the morphologic model (A z =0.678). The performance of a neural network prediction model is comparable to that of an expert radiologist. A neurostatistical approach is preferred for the analysis of diagnostic criteria when many parameters are involved and complex nonlinear relationships exist in the data set.