nils-herrmann/clean_scirepeval huggingface dataset:
The prognostic advantage of preoperative intratumoral injection of OK-432 for gastric cancer patients

To investigate, by a multi-institutional randomized trial, the prognostic significance of the augmentation of tumour-infiltrating lymphocytes (TILs) by preoperative intratumoral injection of OK-432 (OK-432 it), a bacterial biological response modifier, in patients with gastric cancer. The 10-year survival and disease-free survival were examined and analysis of the factors showing survival benefit was performed. 370 patients who had undergone curative resection of gastric cancer were enrolled in this study and followed up for 10 years postoperatively. Patients were randomized into either an OK-432 it group or a control group. Ten Klinishe Einheit (KE) of OK-432 was endoscopically injected at 1 to 2 weeks before the operation in the OK-432 it group. Both groups received the same adjuvant chemoimmunotherapy consisting of a bolus injection of mitomycin C (0.4 mg kg−1i.v.) and administration of tegafur and OK-432 from postoperative day 14 up to 1 year later. Tegafur (600 mg day−1) was given orally and OK-432 (5 KE/2 weeks) was injected intradermally for a maintenance therapy. The TILs grades in resected tumour specimens and presence of metastasis and metastatic pattern in dissected lymph nodes were examined. Multivariate analysis was performed to determine the efficacy of OK-432 it on prognostic factors. All patients were followed up for 10 years. The overall 5- and 10-year survival rates and disease-free survival rates of the OK-432 it group were not significantly higher than those of the control group. However, OK-432 it significantly increased the 5- and 10-year survival rates of patients with stage IIIA + IIIB, moderate lymph node metastasis (pN2), and positive TILs. OK-432 it was most effective at prolonging the survival of patients who had both positive TILs and lymph node metastasis. The OK-432 it group with positive TILs showed a significant decrease in metastatic lymph node frequency and in the number of lymph node micro- metastatic foci when compared to the control group. This study showed that only one time preoperative OK-432 it, particularly when it triggers TILs, is effective for reduction of regional lymph node metastasis. OK-432 it probably acts partly by eliminating micro-metastatic foci in lymph nodes. Preoperative intratumoral injection of OK-432 is technically very easy and has no serious adverse effects, so it is a promising form of neoadjuvant immunotherapy for advanced gastric cancer.
Motor and non motor effects during intraoperative subthalamic stimulation for Parkinson’s disease

Spatial distribution of the clinical effects induced by deep brain stimulation during the intraoperative investigation of the subthalamic nucleus (STN) for Parkinson’s disease (PD) was analysed in 17 patients under local anesthesia. The stimulation parameters were 130 hertz, 100 µs, and voltage ranged from 0.05 to 5 volts. Optimal motor response was assessed as the total and lasting disappearance of wrist rigidity on the side opposite to stimulation.Among the adverse effects induced by stimulation, special attention was given to frequently observed autonomic effects (AE). Full motor response was achieved in 49.2% of the 301 points evaluated,with a mean voltage (MV) of 0.94 volts; paresthesiae occurred in 6.6% (MV: 2 volts), dystonia in 10.6% (MV: 3.4 volts), autonomic effects in 19.6% (MV: 3.1 volts) and oculomotor effects in 31.6% (MV: 3 volts). The motor target was located in the posterodorsal part of the nucleus and the optimal point for motor response was close to the superior limit of the nucleus. Whereas other adverse effects occurred relatively far from the motor target, AE occurred with statistic significance near this point. Their neural substrates, such as limbic system and their relationship with postoperative behavioral disorders, are discussed.
In chronic low back pain, low level laser therapy combined with exercise is more beneficial than exercise alone in the long term: a randomised trial.

Is low level laser therapy an effective adjuvant intervention for chronic low back pain?



Randomised trial with concealed allocation, blinded assessors and intention-to-treat analysis.



Sixty-one patients who had low back pain for at least 12 weeks.



One group received laser therapy alone, one received laser therapy and exercise, and the third group received placebo laser therapy and exercise. Laser therapy was performed twice a week for 6 weeks.



Outcomes were pain severity measured using a 10-cm visual analogue scale, lumbar range of motion measured by the Schober Test and maximum active flexion, extension and lateral flexion, and disability measured with the Oswestry Disability Index on admission to the study, after 6 weeks of intervention, and after another 6 weeks of no intervention.



There was no greater effect of laser therapy compared with exercise for any outcome, at either 6 or 12 weeks. There was also no greater effect of laser therapy plus exercise compared with exercise for any outcome at 6 weeks. However, in the laser therapy plus exercise group pain had reduced by 1.8 cm (95% CI 0.1 to 3.3, p = 0.03), lumbar range of movement increased by 0.9 cm (95% CI 0.2 to 1.8, p < 0.01) on the Schober Test and by 15 deg (95% CI 5 to 25, p < 0.01) of active flexion, and disability reduced by 9.4 points (95% CI 2.7 to 16.0, p = 0.03) more than in the exercise group at 12 weeks.



In chronic low back pain low level laser therapy combined with exercise is more beneficial than exercise alone in the long term.
Maintenance of sinus rhythm after DC reversion of atrial fibrilllation. A double-blind controlled trial of long-acting quinidine bisulphate.

Ninety-two patients were entered in a double-blind controlled trial of long-acting quinidine bisulphate for the maintenance of sinus rhythm following DC reversion of atrial fibrillation. By random selection two statistically comparable groups of patients were obtained, a control group being given a placebo and a treated group quinidine bisulphate 1.5 g. per day in two 12-hourly doses. Thirty-seven patients were followed up in the control group and twenty-eight patients in the treated group. The maintenance of sinus rhythm in the treated group was significantly longer than in the control group, especially during the first three months. The mean serum quinidine level in the treated group was 2.2+/-0.3 (SEM) mg. per litre. There was one death among the patients treated with quinidine, which may have been due to quinidine toxicity caused by a high serum quinidine level.
Efficacy of a modified Stanford V regimen in patients with advanced Hodgkin's lymphoma.

We report treatment results obtained with a modified Stanford V regimen in 32 patients with advanced Hodgkin's lymphoma (stage II bulky disease, III, IV). Treatment results were not superior to those achieved with conventional treatment (ABVD) in terms of complete remission and survival rates (progression-free survival and overall survival at 3 years: 66% and 91%, respectively).
Identification of novel determinants of resistance to lapatinib in ERBB2-amplified cancers

The gene encoding the receptor tyrosine kinase ERBB2, also known as HER2, is amplified and/or overexpressed in up to 15% of breast cancers. These tumours are characterised by an aggressive phenotype and poor clinical outcome. Although therapies targeted at ERBB2 have proven effective, many patients fail to respond to treatment or become resistant and the reasons for this are still largely unknown. Using a high-throughput functional screen we assessed whether genes found to be recurrently amplified and overexpressed in ERBB2+ve breast cancers mediate resistance to the ERBB2-targeted agent lapatinib. Lapatinib-resistant ERBB2-amplified breast cancer cell lines were screened, in the presence or absence of lapatinib, with an RNA interference library targeting 369 genes recurrently amplified and overexpressed in both ERBB2-amplified breast cancer tumours and cell lines. Small interfering RNAs targeting a number of genes caused sensitivity to lapatinib in this context. The mechanisms of resistance conferred by the identified genes were further investigated and in the case of NIBP (TRAPPC9), lapatinib resistance was found to be mediated through NF-κB signalling. Our results indicate that specific amplified and/ or overexpressed genes found in ERBB2-amplified breast cancer may mediate response to ERBB2-targeting agents.
Increased risk of left heart valve regurgitation associated with benfluorex use in patients with diabetes mellitus: a multicenter study.

Benfluorex was withdrawn from European markets in June 2010 after reports of an association with heart valve lesions. The link between benfluorex and valve regurgitations was based on small observational studies and retrospective estimations. We therefore designed an echocardiography-based multicenter study to compare the frequency of left heart valve regurgitations in diabetic patients exposed to benfluorex for at least 3 months and in diabetic control subjects never exposed to the drug.



This reader-blinded, controlled study conducted in 10 centers in France between February 2010 and September 2011 prospectively included 376 diabetic subjects previously exposed to benfluorex who were referred by primary care physicians for echocardiography and 376 diabetic control subjects. Through the use of propensity scores, 293 patients and 293 control subjects were matched for age, sex, body mass index, smoking, dyslipidemia, hypertension, and coronary artery disease. The main outcome measure was the frequency of mild or greater left heart valve regurgitations. In the matched sample, the frequency and relative risk (odds ratio) of mild or greater left heart valve regurgitations were significantly increased in benfluorex patients compared with control subjects: 31.0% versus 12.9% (odds ratio, 3.55; 95% confidence interval, 2.03-6.21) for aortic and/or mitral regurgitation, 19.8% versus 4.7% (odds ratio, 5.29; 95% confidence interval, 2.46-11.4) for aortic regurgitation, and 19.4% versus 9.6% (odds ratio, 2.38; 95% confidence interval, 1.27-4.45) for mitral regurgitation.



Our results indicate that the use of benfluorex is associated with a significant increase in the frequency of left heart valve regurgitations in diabetic patients. The natural history of benfluorex-induced valve abnormalities needs further research.
Frequency doubling perimetry in patients with mild and moderate pituitary tumor-associated visual field defects detected by conventional perimetry.

To test the ability of frequency doubling technology (FDT) perimetry to identify pituitary tumor-associated visual field defects.



Twenty-three eyes from patients with pituitary tumor (PT) and 28 normal eyes were studied. Subjects were eligible when presenting with normal visual acuity and mild or moderate temporal field loss in at least one eye on Goldmann and standard automated perimetry (SAP). FDT testing was performed using the C-20-5 screening and the C-20 full-threshold test. The sensitivity and specificity for identification of the field defect were determined and the groups were compared with regard to several parameters. Finally, we compared the ability of FDT and SAP to detect the characteristic pattern of temporal hemianopia/quadrantanopia.



In the screening test, sensitivity ranged from 21.74% to 43.48% while specificity was 100%. In the threshold test, sensitivity ranged from 52.17% to 82.61% (specificities of 85.71% and 60.71%, respectively), according to total deviation analysis, and from 30.43% to 73.91% (specificities of 96.42% and 64.28%, respectively), according to the pattern deviation analysis. Patients with PT presented a significantly higher number of abnormal points in the temporal hemifield. In 12 eyes FDT and SAP were both able to identify the characteristic pattern of visual field defect; in 4 eyes FDT performed better than SAP; in 4 eyes, SAP performed better than FDT, while in 3 neither test was able to determine the pattern of visual field defect correctly.



Threshold FDT perimetry seems to be a sensitive instrument for identifying abnormality in eyes with chiasmal compression-induced field defects detected on conventional perimetry.
Inflammation’s Association with Metabolic Profiles before and after a Twelve-Week Clinical Trial in Drug-Naïve Patients with Bipolar II Disorder

Inflammation is thought to be involved in the pathophysiology of bipolar disorder (BP) and metabolic syndrome. Prior studies evaluated the association between metabolic profiles and cytokines only during certain mood states instead of their changes during treatment. We enrolled drug-naïve patients with BP-II and investigated the correlation between changes in mood symptoms and metabolic indices with changes in plasma cytokine levels after 12 weeks of pharmacological treatment. Drug-naïve patients (n = 117) diagnosed with BP-II according to DSM-IV criteria were recruited. Metabolic profiles (cholesterol, triglyceride, HbA1C, fasting serum glucose, body mass index (BMI) and plasma cytokines (TNF-α, CRP, IL-6, and TGF-β) were measured at baseline and 2, 8, and 12 weeks post-treatment. To adjust within-subject dependence over repeated assessments, multiple linear regressions with generalized estimating equation methods were used. Seventy-six (65.0%) patients completed the intervention. Changes in plasma CRP were significantly associated with changes in BMI (P = 1.7E-7) and triglyceride (P = 0.005) levels. Changes in plasma TGF-β1 were significantly associated with changes in BMI (P = 8.2E-6), cholesterol (P = 0.004), and triglyceride (P = 0.006) levels. However, changes in plasma TNF-α and IL-6 were not associated with changes in any of the metabolic indices. Changes in Hamilton Depression Rating Scale scores were significantly associated with changes in IL-6 (P = 0.003) levels; changes in Young Mania Rating Scale scores were significantly associated with changes in CRP (P = 0.006) and TNF-α (P = 0.039) levels. Plasma CRP and TGF-β1 levels were positively correlated with several metabolic indices in BP-II after 12 weeks of pharmacological intervention. We also hypothesize that clinical symptoms are correlated with certain cytokines. These new findings might be important evidence that inflammation is the pathophysiology of clinical symptoms and metabolic disturbance in BP-II.
Decompiling Boolean Expressions from Java™ Bytecode

Java bytecode obfuscates the original structure of a Java expression in the source code. So a simple expression such as (c1 || c2) or (c1 && c2) may be captured in the bytecode in 4 different ways (as shown in the paper). And correspondingly, when we reconvert the bytecode back into Java source code, there are four different ways this may happen. Further, although gotos are not permitted in the Java source code, the bytecode is full of gotos. If you were to blindly convert the bytecode into Java source code, then you would replace a goto by a labeled break. A labeled break has the advantage that it only allows you to break out of a block structure and (unlike a setjump) does not permit you to jump arbitrarily into a block structure. So while the data structures used in the regenerated Java source code are still relatively "clean" arbitrary usage of labeled breaks makes for unreadable code (as we show in the paper). And this can be a point of concern, since decompilation is generally related to debugging code.
 Instead of dumping arbitrary labeled breaks, we try to reconstruct the original expression, in terms of && and || clauses as well as ternary operators "?:" (c0 ? c1 : c2);& and || clauses as well as ternary operators "?:" (c0 ? c1 : c2); Thus our goal is quite simply to regenerate, without using goto or labeled breaks, the expressions as close to the original as possible (it is not possible to guarantee an exact match). In this paper we explain what is the state of the art in Java decompilers for decoding complex expressions. Then we will present our solution. We have implemented the algorithms described here in this paper and give you our experience with it.
Noninferiority of a task-shifting HIV care and treatment model using peer counselors and nurses among Ugandan women initiated on ART: evidence from a randomized trial.

To assess the noninferiority of a task-shifting HIV treatment model relying on peer counselors and nurses compared with a physician-centered model among HIV-1-positive women initiated on antiretroviral therapy (ART) at a prevention of mother-to-child transmission clinic in Mulago Hospital, Uganda.



HIV-1-infected ART eligible naive women were randomized to either nurse-peer (intervention) or doctor-counselor (standard model) arm. The primary endpoint was virologic success defined attaining a viral load < 400 RNA copies per milliliter 6-12 months after ART initiation. Noninferiority was defined as the lower 95% confidence limit for the difference in proportions with virologic success being less than 10%. Secondary outcomes included immunologic success (mean CD4 count increase from baseline) and pill count.



Data on 85 participants were analyzed (n = 45 in the intervention and n = 40 in the standard model). The proportion of participants with virologic success was similar in the standard and intervention models [91% versus 88% respectively; difference, 3%; 95% confidence interval (CI): -11% to 12%]. Probability of viral detection at 6-12 months' time point was similar in the 2 models (log-rank test P = 0.73). Immunologic and pill count indicators were also similar in the intervention and standard models, with mean CD4 increase of 217 versus 206 cells per microliter (difference, 11; 95% CI: -60 to 82 cells/μL) and pill counts of 99.8% versus 99.7% (difference, 0.0; 95% CI: -5% to 5%) respectively.



Nurses and peer counselors were not inferior in providing ART follow-up care to postpartum women, an approach that may help deliver treatment to many more HIV-infected people.
Association of Depression with Disease Severity in Patients with Chronic Obstructive Pulmonary Disease

Patients with chronic obstructive pulmonary disease (COPD), which is predicted to be the third most common cause of death worldwide by 2020, often suffer from depression, one of the most common and modifiable comorbidities of COPD. This study assessed the prevalence of depression in patients with COPD and the association of depression with disease severity. This was a multicenter, prospective cross-sectional study of 245 patients with stable COPD. Disease severity was assessed using two scales: the global initiative for chronic obstructive lung disease (GOLD) stage and BODE index. Depression was measured using the Centers for Epidemiologic Studies Depression (CES-D) scales. Data were analyzed using descriptive statistics, Spearman correlation, and multivariate logistic regression. Depression defined as a CES-D score of 24 and higher was observed in 17.6 % of patients with COPD. The prevalence of depression increased with disease severity based on the BODE quartile (r = 0.16; P = 0.014). By contrast, no difference was observed in the prevalence of depression among the severity groups using the GOLD staging system (r = − 0.01; P = 0.898). Elementary school graduates were more likely to experience depression than graduates of high school and above [odds ratio (OR) = 3.67; 95 % confidence interval (CI) 1.37–9.85] and patients in BODE quartile II were more likely to experience depression than those with BODE quartile I (OR = 2.5; 95 % CI  1.04–6.06). Depression was associated with disease severity according to the BODE quartile in patients with COPD. BODE quartile II was a significant predictor of depression. Screening patients with a high risk of depression and proactive intervention for those patients are needed.
Hyperbaric oxygenation accelerates the healing rate of nonischemic chronic diabetic foot ulcers: a prospective randomized study.

To study the effect of systemic hyperbaric oxygenation (HBO) therapy on the healing course of nonischemic chronic diabetic foot ulcers.



From 1999 to 2000, 28 patients (average age 60.2 +/- 9.7 years, diabetes duration 18.2 +/- 6.6 years), of whom 87% had type 2 diabetes, demonstrating chronic Wagner grades I-III foot ulcers without clinical symptoms of arteriopathy, were studied. They were randomized to undergo HBO because their ulcers did not improve over 3 months of full standard treatment. All the patients demonstrated signs of neuropathy. HBO was applied twice a day, 5 days a week for 2 weeks; each session lasted 90 min at 2.5 ATA (absolute temperature air). The main parameter studied was the size of the foot ulcer measured on tracing graphs with a computer. It was evaluated before HBO and at day 15 and 30 after the baseline.



HBO was well tolerated in all but one patient (barotraumatic otitis). The transcutaneous oxygen pressure (TcPO(2)) measured on the dorsum of the feet of the patients was 45.6 +/- 18.1 mmHg (room air). During HBO, the TcPO(2) measured around the ulcer increased significantly from 21.9 +/- 12.1 to 454.2 +/- 128.1 mmHg (P < 0.001). At day 15 (i.e., after completion of HBO), the size of ulcers decreased significantly in the HBO group (41.8 +/- 25.5 vs. 21.7 +/- 16.9% in the control group [P = 0.037]). Such a difference could no longer be observed at day 30 (48.1 +/- 30.3 vs. 41.7 +/- 27.3%). Four weeks later, complete healing was observed in two patients having undergone HBO and none in the control group.



In addition to standard multidisciplinary management, HBO doubles the mean healing rate of nonischemic chronic foot ulcers in selected diabetic patients. The time dependence of the effect of HBO warrants further investigations.
Increased urinary 15-F2t-isoprostane concentrations in patients with non-ischaemic congestive heart failure: a marker of oxidative stress.

To investigate a novel marker of oxidative stress in patients with congestive heart failure (CHF).



15 patients with mild CHF, 15 patients with severe CHF with acute exacerbation, and 15 control subjects.



Measurement of urinary 15-F2t-isoprostane, plasma brain natriuretic peptide (BNP), serum interleukin 6 (IL-6), and serum thrombomodulin concentrations. In patients with severe CHF, samples were taken at admission and 4, 7, and 14 days after admission.



Urinary 15-F2t-isoprostane, plasma BNP, and serum IL-6 concentrations in patients with severe CHF were significantly higher than those in control subjects or in patients with mild CHF. However, concentrations of serum thrombomodulin, a marker of endothelial damage, were not different between patients with CHF and control subjects. In addition, urinary 15-F2t-isoprostane, plasma BNP, and serum IL-6 concentrations in patients with severe CHF gradually decreased in proportion to the severity of CHF during hospitalisation. Interestingly, urinary 15-F2t-isoprostane concentrations significantly correlated with plasma BNP concentrations and serum IL-6 concentrations, but not with serum thrombomodulin concentrations.



Urinary 15-F2t-isoprostane concentrations increased in proportion to the severity of CHF in patients. This may be caused by increased 15-F2t-isoprostane production. These findings suggest that urinary 15-F2t-isoprostane may be a marker of morbidity as well as oxidative stress in patients with CHF.
Role of mouthguards in reducing mild traumatic brain injury/concussion incidence in high school football athletes.

There is continued speculation on the value of mouthguards (MGs) in preventing mild traumatic brain injury (MTBI)/concussion injuries. The purpose of this randomized prospective study was to compare the impact of pressure-laminated (LM), custom-made, properly fitted MGs to over-the-counter (OTC) MGs on the MTBI/concussion incidence in high school football athletes over a season of play. Four hundred twelve players from 6 high school football teams were included in the study. Twenty-four MTBI/concussion injuries (5.8%) were recorded. When examining the MTBI/concussion injury rate by MG type, there was a significant difference (P = 0.0423) with incidence rates of 3.6% and 8.3% in the LM MG and OTC MG groups, respectively.