nils-herrmann/clean_scirepeval huggingface dataset:
Adding ascorbic acid to arsenic trioxide produces limited benefit in patients with acute myeloid leukemia excluding acute promyelocytic leukemia

Arsenic trioxide (ATO) is highly effective in acute promyelocytic leukemia (APL), but despite its multiple mechanism of action, it has no activity in acute myeloid leukemia (AML) that excludes APL (non-APL AML). Ascorbic acid (AA) and ATO induces apoptosis in AML cell lines by depleting intracellular glutathione and generation of reactive oxygen species. In this study, we evaluated the effect of ATO plus AA in patients with non-APL AML. The study enrolled patient aged 18 or older with relapsed or refractory AML (non-APL) after conventional chemotherapy or previously untreated patients 55 years or older who were unfit for standard induction chemotherapy for AML. Intravenous ATO (0.25 mg/kg/day over 1–4 h) was given with intravenous AA (1 g/day over 30 min after ATO) for 5 days a week for 5 weeks (25 doses).  AML patients were enrolled, including six previously untreated elderly patients aged 66–84 years in whom five had antecedent hematological disorder (ADH). Among 10 evaluable patients, one achieved a CR one a CRi and 4 patients had disappearance of blasts from peripheral blood and bone marrow. Five of the six responders were seen in previously untreated elderly patients. ATO related toxicity was mild. The combination of ATO and AA has limited clinical meaningful antileukemia activity in patients with non-APL AML.
An Augmented Reality System Validation for the Treatment of Cockroach Phobia

Augmented reality (AR) is a new technology in which various virtual elements are incorporated into the user's perception of the real world. The most significant aspect of AR is that the virtual elements add relevant and helpful information to the real scene. AR shares some important characteristics with virtual reality as applied in clinical psychology. However, AR offers additional features that might be crucial for treating certain problems. An AR system designed to treat insect phobia has been used for treating phobia of small animals, and positive preliminary data about the global efficacy of the system have been obtained. However, it is necessary to determine the capacity of similar AR systems and their elements that are designed to evoke anxiety in participants; this is achieved by testing the correspondence between the inclusion of feared stimuli and the induction of anxiety. The objective of the present work is to validate whether the stimuli included in the AR-Insect Phobia system are capable of inducing anxiety in six participants diagnosed with cockroach phobia. Results support the adequacy of each element of the system in inducing anxiety in all participants.
Randomized clinical trial comparing high versus standard dose of ribavirin plus peginterferon alfa-2a in hepatitis C genotype 3 and high viral load. Dargen-3 study.

Less than half of patients with chronic hepatitis C genotype 3 (G3) and high viral load (HVL) without a rapid virological response (RVR) achieve a sustained virological response (SVR) when treated with peginterferon plus ribavirin (RBV).



To assess the impact of high doses of RBV on SVR in patients with G3 and HVL.



Ninety-seven patients were randomized to receive peginterferon α-2a+RBV 800 mg/day (A; n=42) or peginterferon α-2a+RBV 1600 mg/day+epoetin β 400 IU/kg/week SC (B; n=55). Patients allocated to group B who achieved RVR continued on RBV (800mg/day) for a further 20 weeks (B1; n=42) while non-RVR patients received a higher dose of RBV (1600 mg/day)+epoetin β (B2; n=13).



RVR was observed in 64.3% of patients in A and in 76.4% in B (p=0.259). Intention-to-treat (ITT) analysis showed SVR rates of 64.3% (A) and 61.8% (B), with a reduction of -2.5% (-21.8% to 16.9%) (p=0.835). The SVR rate was 61.9% in arm B1 and 61.5% in arm B2. No serious adverse events were reported, and the rate of moderate adverse events was < 5%.



G3 patients with high viral load without RVR did not obtain a benefit from a higher dose of RBV. Higher doses of RBV plus epoetin β were safe and well tolerated (
Quantitative trait loci predicting circulating sex steroid hormones in men from the NCI-Breast and Prostate Cancer Cohort Consortium (BPC3).

Twin studies suggest a heritable component to circulating sex steroid hormones and sex hormone-binding globulin (SHBG). In the NCI-Breast and Prostate Cancer Cohort Consortium, 874 SNPs in 37 candidate genes in the sex steroid hormone pathway were examined in relation to circulating levels of SHBG (N = 4720), testosterone (N = 4678), 3 alpha-androstanediol-glucuronide (N = 4767) and 17beta-estradiol (N = 2014) in Caucasian men. rs1799941 in SHBG is highly significantly associated with circulating levels of SHBG (P = 4.52 x 10(-21)), consistent with previous studies, and testosterone (P = 7.54 x 10(-15)), with mean difference of 26.9 and 14.3%, respectively, comparing wild-type to homozygous variant carriers. Further noteworthy novel findings were observed between SNPs in ESR1 with testosterone levels (rs722208, mean difference = 8.8%, P = 7.37 x 10(-6)) and SRD5A2 with 3 alpha-androstanediol-glucuronide (rs2208532, mean difference = 11.8%, P = 1.82 x 10(-6)). Genetic variation in genes in the sex steroid hormone pathway is associated with differences in circulating SHBG and sex steroid hormones.
A prospective multicenter study of systemic reactions in standardized specific immunotherapy for allergic rhinitis in China.

Standardized allergen-specific immunotherapy (SIT) has been used in China for years. However, there is no extensive study of the safety of standardized SIT in Chinese patients until now. The aim of the current study is to perform a prospective and multicenter study to evaluate the systemic reactions (SRs) of standardized SIT in Chinese patients.



The study was performed in 13 allergy centers in China, using the same vaccine and practice procedure. The length of observation period was 2 years. SRs were recorded and analyzed.



There were 666 patients included (261 children and 405 adults). All patients finished the initial phase and 47 patients withdrew during the maintenance phase. There were 0.47% (94/19,963) SRs in all injections (0.72% in children and 0.31% in adults); 8.26% (55/666) patients experienced SRs (12.26% children and 5.68% adults). The occurrence of SRs was significantly higher in children than that in adults (p < 0.01). A higher ratio of SRs was found among patients accompanied with asthma. There were 74.47% SRs of grade I, 15.96% SRs of grade II, 7.45% SRs of grade III, and 2.13% SRs of grade IV. There were 90.43% of SRs associated with the discomfort of lower respiratory tract.



This multicenter study showed that properly conducted standardized SIT was a safe treatment for allergic rhinitis in China. The incidence of SRs was higher in children than that in adults.
Model-based optimal PEEP in mechanically ventilated ARDS patients in the Intensive Care Unit

The optimal level of positive end-expiratory pressure (PEEP) is still widely debated in treating acute respiratory distress syndrome (ARDS) patients. Current methods of selecting PEEP only provide a range of values and do not provide unique patient-specific solutions. Model-based methods offer a novel way of using non-invasive pressure-volume (PV) measurements to estimate patient recruitability. This paper examines the clinical viability of such models in pilot clinical trials to assist therapy, optimise patient-specific PEEP, assess the disease state and response over time.



Ten patients with acute lung injury or ARDS underwent incremental PEEP recruitment manoeuvres. PV data was measured at increments of 5 cmH2O and fitted to the recruitment model. Inspiratory and expiratory breath holds were performed to measure airway resistance and auto-PEEP. Three model-based metrics are used to optimise PEEP based on opening pressures, closing pressures and net recruitment. ARDS status was assessed by model parameters capturing recruitment and compliance.



Median model fitting error across all patients for inflation and deflation was 2.8% and 1.02% respectively with all patients experiencing auto-PEEP. In all three metrics' cases, model-based optimal PEEP was higher than clinically selected PEEP. Two patients underwent multiple recruitment manoeuvres over time and model metrics reflected and tracked the state or their ARDS.



For ARDS patients, the model-based method presented in this paper provides a unique, non-invasive method to select optimal patient-specific PEEP. In addition, the model has the capability to assess disease state over time using these same models and methods.
A synovectomy trial and the history of early knee synovitis in rheumatoid arthritis

The results of a randomized synovectomy trial are reported and the history of early knee synovitis in 121 patients with rheumatoid arthritis is described. Conservative treatment (rest in splints, non-steroidal anti-inflammatory drugs and gold or an anti-malaria agent) for 4–5 months led to improvement in 81 of the 121 patients with early knee synovitis. In one-third of these 81 patients, the improvement continued, according to their own and the doctor's opinion, during 5 years of follow-up. Ten of the 22 patients who fulfilled the criteria for the synovectomy trial were operated upon. They showed improvement for 4 years. Over the 5-year period, two-thirds of the group were constantly seropositive or seronegative and in the other third the serology varied, but such that at each assessment 50% of the group were seropositive. Radiologically, all of the patients showed deterioration. The surgical group deteriorated more slowly for the first 2–3 years, but then showed the same pattern as the other groups. The disappearance of the clinical features of synovitis does not mean that radiological deterioration has ceased.
Effects of a green tea extract, Polyphenon E, on systemic biomarkers of growth factor signalling in women with hormone receptor-negative breast cancer.

Observational and experimental data support a potential breast cancer chemopreventive effect of green tea.



We conducted an ancillary study using archived blood/urine from a phase IB randomised, placebo-controlled dose escalation trial of an oral green tea extract, Polyphenon E (Poly E), in breast cancer patients. Using an adaptive trial design, women with stage I-III breast cancer who completed adjuvant treatment were randomised to Poly E 400 mg (n = 16), 600 mg (n = 11) and 800 mg (n = 3) twice daily or matching placebo (n = 10) for 6 months. Blood and urine collection occurred at baseline, and at 2, 4 and 6 months. Biological endpoints included growth factor [serum hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF)], lipid (serum cholesterol, triglycerides), oxidative damage and inflammatory biomarkers.



From July 2007-August 2009, 40 women were enrolled and 34 (26 Poly E, eight placebo) were evaluable for biomarker endpoints. At 2 months, the Poly E group (all dose levels combined) compared to placebo had a significant decrease in mean serum HGF levels (-12.7% versus +6.3%, P = 0.04). This trend persisted at 4 and 6 months but was no longer statistically significant. For the Poly E group, serum VEGF decreased by 11.5% at 2 months (P = 0.02) and 13.9% at 4 months (P = 0.05) but did not differ compared to placebo. At 2 months, there was a trend toward a decrease in serum cholesterol with Poly E (P = 0.08). No significant differences were observed for other biomarkers.



Our findings suggest potential mechanistic actions of tea polyphenols in growth factor signalling, angiogenesis and lipid metabolism.
High Sodium Intake Is Associated With Self-Reported Rheumatoid Arthritis: A Cross Sectional and Case Control Analysis Within the SUN Cohort

Sodium intake is a potential environmental factor for immune-mediated inflammatory diseases. The aim of this study is to investigate the association of sodium intake with rheumatoid arthritis. We performed a cross-sectional study nested in a highly educated cohort investigating dietary habits as determinants of disease. Daily sodium intake in grams per day was estimated from a validated food frequency questionnaire. We identified prevalent self-reported cases of rheumatoid arthritis. Logistic regression models were used to estimate the odds ratio for rheumatoid arthritis by sodium intake adjusting for confounders. Linear trend tests and interactions between variables were explored. Sensitivity analyses included age- and sex-matched case-control study, logistic multivariate model adjusted by residuals, and analysis excluding individuals with prevalent diabetes or cardiovascular disease. The effective sample size was 18,555 individuals (mean age 38-years old, 60% women) including 392 self-reported rheumatoid arthritis. Median daily sodium intake (estimated from foods plus added salt) was 3.47 (P25-75: 2.63-4.55) grams. Total sodium intake in the fourth quartile showed a significant association with rheumatoid arthritis (fully adjusted odds ratio 1.5; 95% CI 1.1-2.1, P for trend = 0.02). Never smokers with high sodium intake had higher association than ever smokers with high sodium intake (P for interaction = 0.007). Dose-dependent association was replicated in the case-control study. High sodium intake may be associated with a diagnosis of rheumatoid arthritis. This confirms previous clinical and experimental research.
Chronic obstructive pulmonary disease in the older adult: what defines abnormal lung function?

The Global Initiative on Obstructive Lung Disease stages for chronic obstructive pulmonary disease (COPD) uses a fixed ratio of the post-bronchodilator forced expiratory volume in 1 second (FEV(1))/forced vital capacity (FVC) of 0.70 as a threshold. Since the FEV(1)/FVC ratio declines with age, using the fixed ratio to define COPD may "overdiagnose" COPD in older populations.



To determine morbidity and mortality among older adults whose FEV(1)/FVC is less than 0.70 but more than the lower limit of normal (LLN).



The severity of COPD was classified in 4965 participants aged > or =65 years in the Cardiovascular Health Study using these two methods and the age-adjusted proportion of the population who had died or had a COPD-related hospitalisation in up to 11 years of follow-up was determined.



1621 (32.6%) subjects died and 935 (18.8%) had at least one COPD-related hospitalisation during the follow-up period. Subjects (n = 1134) whose FEV(1)/FVC fell between the LLN and the fixed ratio had an increased adjusted risk of death (hazard ratio (HR) 1.3, 95% CI 1.1 to 1.5) and COPD-related hospitalisation (HR 2.6, 95% CI 2.0 to 3.3) during follow-up compared with asymptomatic individuals with normal lung function.



In this cohort, subjects classified as "normal" using the LLN but abnormal using the fixed ratio were more likely to die and to have a COPD-related hospitalisation during follow-up. This suggests that a fixed FEV(1)/FVC ratio of <0.70 may identify at-risk patients, even among older adults.
Postprandial hyperglycemia impairs vascular endothelial function in healthy men by inducing lipid peroxidation and increasing asymmetric dimethylarginine:arginine.

Postprandial hyperglycemia induces vascular endothelial dysfunction (VED) and increases future cardiovascular disease risk. We hypothesized that postprandial hyperglycemia would decrease vascular function in healthy men by inducing oxidative stress and proinflammatory responses and increasing asymmetric dimethylarginine:arginine (ADMA:arginine), a biomarker that is predictive of reduced NO biosynthesis. In a randomized, cross-over design, healthy men (n = 16; 21.6 ± 0.8 y) ingested glucose or fructose (75 g) after an overnight fast. Brachial artery flow-mediated dilation (FMD), plasma glucose and insulin, antioxidants, malondialdehyde (MDA), inflammatory proteins, arginine, and ADMA were measured at regular intervals during the 3-h postprandial period. Baseline FMD did not differ between trials (P > 0.05). Postprandial FMD was reduced following the ingestion of glucose only. Postprandial MDA concentrations increased to a greater extent following the ingestion of glucose compared to fructose. Plasma arginine decreased and the ratio of ADMA:arginine increased to a greater extent following the ingestion of glucose. Inflammatory cytokines and cellular adhesion molecules were unaffected by the ingestion of either sugar. Postprandial AUC(0-3 h) for FMD and MDA were inversely related (r = -0.80; P < 0.05), suggesting that hyperglycemia-induced lipid peroxidation suppresses postprandial vascular function. Collectively, these findings suggest that postprandial hyperglycemia in healthy men reduces endothelium-dependent vasodilation by increasing lipid peroxidation independent of inflammation. Postprandial alterations in arginine and ADMA:arginine also suggest that acute hyperglycemia may induce VED by decreasing NO bioavailability through an oxidative stress-dependent mechanism. Additional work is warranted to define whether inhibiting lipid peroxidation and restoring arginine metabolism would mitigate hyperglycemia-mediated decreases in vascular function.
Randomised trial of the effects of four weeks of daily stretch on extensibility of hamstring muscles in people with spinal cord injuries.

The aim of this assessor-blind randomised controlled trial was to determine the effect of four weeks of 30 minute stretches each weekday on extensibility of the hamstring muscles in people with recent spinal cord injuries. A consecutive sample of 16 spinal cord-injured patients with no or minimal voluntary motor power in the lower limbs and insufficient hamstring muscle extensibility to enable optimal long sitting were recruited. Subjects' legs were randomly allocated to experimental and control conditions. The hamstring muscles of the experimental leg of each subject were stretched with a 30 Nm torque at the hip for 30 minutes each weekday for four weeks. The hamstring muscles of the contralateral leg were not stretched during this period. Extensibility of the hamstring muscles (hip flexion range of motion with knee extended, measured with a 48 Nm torque at the hip) of both legs was measured by a blinded assessor at the commencement of the study and one day after the completion of the four-week stretch period. Changes in hamstring muscle extensibility from initial to final measurements were calculated. The effect of stretching was expressed as the mean difference in these changes between stretched and non-stretched legs. The mean effect of stretching was 1 degree (95% CI -2 to 5 degrees). Four weeks of 30 minute stretches each weekday does not affect the extensibility of the hamstring muscle in people with spinal cord injuries.
Adherence is not a barrier to successful antiretroviral therapy in South Africa.

To determine adherence of an indigent African HIV-infected cohort initiating antiretroviral therapy (ART); to identify predictors of incomplete adherence (< 95%) and virologic failure (> 400 HIV RNA copies/ml).



Prospective monitoring of adherence in a poor HIV-positive cohort, attending a public sector hospital and receiving ART through phase III studies.



Adherence to ART was determined over 48 weeks by counting tablet-returns. Logistic regression models including age, WHO HIV stage, home language, socio-economic status, complexity and type of regimen were fitted to determine predictors of incomplete adherence and virologic failure at 48 weeks.



289 patients were recruited between January 1996 and May 2001. Median (mean) adherence of the cohort was 93.5% (87.2%). Three times daily dosing [risk ratio (RR), 3.07; 95% confidence interval (CI), 1.40-6.74], speaking English (RR, 0.41; 95% CI, 0.21-0.80) and age (RR, 0.97; 95% CI, 0.94-0.99) were independent predictors of incomplete adherence. Socio-economic status, sex and HIV stage did not predict adherence. Independent predictors of virologic failure included baseline viral load (RR, 2.57; 95% CI, 1.57-4.22) and three times daily dosing (RR, 2.64; 95% CI, 1.23-5.66), incomplete adherence (RR, 1.92; 95% CI, 1.10-3.57), age (RR, 0.96; 95% CI, 0.92-0.99) and dual nucleoside therapy (RR, 2.69; 95% CI, 1.17-6.15).



The proportion of individuals achieving viral suppression matched results from the developing world. Speaking the same language as site staff and simplified dosing frequency were beneficial. Socio-economic status had no impact on adherence and should not be used as a limitation to ART access.
Effects of angiotensin type-1 receptor antagonism on small artery function in patients with type 2 diabetes mellitus.

Endothelial dysfunction has been demonstrated to occur in small arteries from patients with type 2 diabetes and hypertension. The effects of angiotensin II receptor blockade on vessel function were examined using pressure myography in a randomized 12-week double-blind placebo-controlled parallel group study using candesartan cilexitil. The maximal vascular response to acetylcholine (Ach) was impaired at baseline and improved with candesartan. This improvement was primarily caused by an effect in the nitric oxide component of Ach-mediated dilatation. The degree of endothelial dysfunction directly correlated with serum low-density lipoprotein cholesterol levels. Sodium nitroprusside-induced endothelium-independent dilatation was reduced in diabetic patients and intervention with candesartan lead to an improvement in EC50 with no change in maximal response. Vasoconstriction to norepinephrine was normal and did not change with intervention, but responses to angiotensin II were reduced after candesartan in diabetic patients. These results demonstrate that even brief treatment with angiotensin II receptor blockade is associated with a significant improvement in resistance vessel endothelial function.
A clinical staging score to measure the severity of dialysis-related amyloidosis

The ongoing effort to prevent dialysis-related amyloidosis (DRA) has been hampered by lack of any way to measure DRA’s severity. Yet, such measurement is essential for assessing the effect of DRA treatment. Accordingly, we developed a scoring system focused on the physical manifestations of DRA. Forty-four patients on maintenance hemodialysis with DRA, and 96 without it, were enrolled. The SF-36v2 Health Survey ascertained whether patients experienced general bodily pain and/or physical dysfunction with any attendant specific pain (dysfunction). If so, the association of those conditions with a finding of DRA was analyzed—including laboratory and radiographic data—and a scoring system reflecting the extent of that dysfunction was devised using the significant variables in the multivariate analysis. Both dysfunction and general bodily pain were severe in patients with DRA. Presence of polyarthralgia, trigger finger, carpal tunnel syndrome (CTS), and dialysis-related spondyloarthropathy (DRS) were associated with that dysfunction after appropriate adjustments. The new scoring system used those four variables in the model, with a 3 given for polyarthralgia and DRS, and 2 for trigger finger and CTS (possible range 0–10). Based on the physical functioning score of SF-36v2, we categorized A-score into three stages: mild (A-score 3–4), moderate (5–7), and severe (8–10). The corresponding area under the receiver-operating characteristics curve for diagnosis of DRA was 0.9345 when we set the cutoff value as 4. This validated scoring system for quantitatively estimating the severity of DRA can serve as A useful measure in clinical practice.