nils-herrmann/clean_scirepeval huggingface dataset:
Phase I study of Carzelesin (U-80,244) given (4-weekly) by intravenous bolus schedule

SummaryCarzelesin is a cyclopropylpyrroloindole analogue which acts as a DNA-sequence-specific alkylating agent. In this phase I study, Carzelesin was given as a 4-weekly 10 min IV infusion to 51 patients with advanced solid tumours. Patients received a median of two courses (range 1–5) at one of nine dose levels: 24, 48, 96, 130, 150, 170, 210, 250 and 300 μg m–2. According to NCI-CTC criteria, non-haematological toxicities (grade 1/2) included fever, nausea and vomiting, mucositis and anorexia, none of which was clearly dose related. The dose-limiting toxicity was haematological and consisted mainly of neutropenia and to a lesser extent thrombocytopenia. From the dose level 150 μg m–2, the haematological toxicity (particularly thrombocytopenia) was delayed in onset, prolonged and cumulative in some patients. In several courses, double WBC nadirs occurred. The maximum tolerated dose for a single course was 300 μg m–2. From the dose level 170 μg m–2, the intended dose intensity could not be delivered to most patients receiving > 2 courses owing to cumulative haematological toxicity. The dose level with the best dose intensity for multiple courses was 150 μg m–2. The pharmacokinetics of Carzelesin and its metabolites (U-76,073; U-76,074) have been established in 31 patients during the first course of treatment using a HPLC method. Carzelesin exhibited linear pharmacokinetics. The concentration of U-76,074 (active metabolite) extended above the lower limit of quantitation (1 ng ml–1) for short periods of time and only at the higher dose levels. There was no relationship between neutropenia and the AUC of the prodrug Carzelesin, but the presence of detectable plasma levels of the active metabolite U-76,074 was usually associated with a substantial decrease in ANC values.
Spirometry-Adjusted Fraction of Exhaled Nitric Oxide Allows Asthma Diagnosis in Children, Adolescents, and Young Adults.

Recently, it has been proved that fractional exhaled nitric oxide (FENO) results are in disagreement with other measurements of asthma control. The objective of this work is to present and validate new lung function/lung inflammation ratios.



This is a retrospective, cross-sectional study in which we evaluated data from medical documentation of 1,529 pediatric and adolescent subjects and a small number (2% of the studied population) of young adults, who presented symptoms suggestive of asthma (age range 4-24 y). We are the first to analyze results obtained in this manner (before the introduction of controlled medication): FENO, spirometry, specific resistance of the airways, diagnosis of allergic diseases, and allergen sensitization (specific immunoglobulin E results).



Cut-off points for the new indicators allowed us to diagnose asthma in the study participants: for FVC/FENO ratio, 0.17 L/ppb; for FEV1/FENO ratio, 0.15 L/ppb; for forced expiratory flow during the middle half of the FVC maneuver (FEF25-75%)/FENO ratio, 0.16 L/s/ppb; for FENO/FVC ratio, 11.00 ppb/L; for FENO/FEV1 ratio, 12.53 ppb/L; and for FENO/FEF25-75% ratio, 11.81 ppb/L/s. Only the ratios described above were closely correlated with the diagnosis of asthma and with one another. They significantly differed between subjects with asthma and healthy subjects as well as between females and males. Only FEF25-75%/FENO and FENO/FEF25-75% values were significant predictors of any sensitization in the studied subjects. We found higher sensitivity than specificity and higher positive predictive value than negative predictive value for FVC/FENO, FEV1/FENO, and FEF25-75%/FENO and found a mirror image for reverse parameters. However, the positive predictive values and negative predictive values were not clearly convincing with respect to diagnostic accuracy in the case of the new parameters proposed.



We propose new lung function/lung inflammation ratios by which it may become possible to diagnose asthma in children and adolescents on the basis of a subject's spirometry and FENO measurements. We believe that our ratios are only supportive of the universally used parameters in the process of diagnosing asthma.
Identification of epigenetically regulated genes that predict patient outcome in neuroblastoma

Epigenetic mechanisms such as DNA methylation and histone modifications are important regulators of gene expression and are frequently involved in silencing tumor suppressor genes. In order to identify genes that are epigenetically regulated in neuroblastoma tumors, we treated four neuroblastoma cell lines with the demethylating agent 5-Aza-2'-deoxycytidine (5-Aza-dC) either separately or in conjunction with the histone deacetylase inhibitor trichostatin A (TSA). Expression was analyzed using whole-genome expression arrays to identify genes activated by the treatment. These data were then combined with data from genome-wide DNA methylation arrays to identify candidate genes silenced in neuroblastoma due to DNA methylation. We present eight genes (KRT19, PRKCDBP, SCNN1A, POU2F2, TGFBI, COL1A2, DHRS3 and DUSP23) that are methylated in neuroblastoma, most of them not previously reported as such, some of which also distinguish between biological subsets of neuroblastoma tumors. Differential methylation was observed for the genes SCNN1A (p < 0.001), PRKCDBP (p < 0.001) and KRT19 (p < 0.01). Among these, the mRNA expression of KRT19 and PRKCDBP was significantly lower in patients that have died from the disease compared with patients with no evidence of disease (fold change -8.3, p = 0.01 for KRT19 and fold change -2.4, p = 0.04 for PRKCDBP). In our study, a low methylation frequency of SCNN1A, PRKCDBP and KRT19 is significantly associated with favorable outcome in neuroblastoma. It is likely that analysis of specific DNA methylation will be one of several methods in future patient therapy stratification protocols for treatment of childhood neuroblastomas.
Enteral nutrition is superior to total parenteral nutrition for pancreatic cancer patients who underwent pancreaticoduodenectomy.

To determine the effects of total parenteral nutrition (TPN) and enteral nutrition (EN) on biochemical and clinical outcomes in pancreatic cancer patients who underwent pancreaticoduodenectomy.



From the year 2006 to 2008, 60 patients who underwent pancreaticoduodenectomy in Tianjin Third Central Hospital were enrolled in this study. They were randomly divided into the EN group and the TPN group. The biochemical and clinical parameters were recorded and analyzed between the two groups.



There was no significant difference in the nutritional status, liver and kidney function, and blood glucose levels between the TPN and EN groups on the preoperative day, the 1st and 3 rd postoperative days. However, on the 7th postoperative day, there was significant difference between the two groups in 24 h urinary nitrogen, serum levels of, total protein (TP), transferrin (TF), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and γ-glutamyl transpeptadase (GGT), blood urea nitrogen (BUN) and creatinine (Cr). On the 14th postoperative day, there was a significant difference between the two groups in terms of urinary levels of 24 h nitrogen, TP, TF, retinol binding protein, ALT, AST, ALP, GGT, total bilirubin, direct bilirubin, BUN, Cr, and glucose. The incidence of delayed gastric emptying in the EN and TPN groups was 0% and 20%, respectively. Moreover, the incidence of pancreatic fistulas and hemorrhages in the EN group were 3.6% and 3.6%, versus 26.7% and 30% in the TPN group, respectively.



EN is better than TPN for pancreatic cancer patients who received pancreaticoduodenectomy.
Translation and validation of the EORTC brain cancer module ( EORTC QLQ-BN 20 ) for use in Iran

The aim of this study was to translate the EORTC quality of life questionnaire for brain cancer, the QLQ-BN20, into Persian, and to evaluate its psychometric properties when used among brain cancer patients in Iran.  A standard backward and forward translation procedure was used to generate the Persian language version of the QLQ-BN20. The QLQ-BN20 was administered together with the QLQ-C30 to 194 patients diagnosed with primary brain cancer. Multitrait scaling and confirmatory factor analysis (CFA) were used to evaluate the hypothesized scale structure of the questionnaire. Internal consistency reliability was estimated with Cronbach’s alpha. The ability of the QLQ-BN20 to distinguish between patient subgroups formed on the basis of performance status and cognitive status was evaluated, as was the responsiveness of the questionnaire to changes in performance status over time.  Multitrait scaling and CFA results confirmed the hypothesized scale structure. The measurement model was consistent across men and women. Internal consistency reliability of the multi-item scales ranged from 0.74 to 0.89. The QLQ-BN20 distinguished clearly between patients with relatively good versus poor performance and cognitive status, and changes in scores over time reflected changes observed in performance status ratings.  These results support the validity and reliability of the QLQ-BN20 for use among Iranian patients diagnosed with primary brain cancer. Future studies should examine the psychometrics of the questionnaire when used in patients with brain metastasis.
Gender Differences in Radiation Dose From Nuclear Cardiology Studies Across the World: Findings From the INCAPS Registry.

The aim of this study was to investigate gender-based differences in nuclear cardiology practice globally, with a particular focus on laboratory volume, radiation dose, protocols, and best practices.



It is unclear whether gender-based differences exist in radiation exposure for nuclear cardiology procedures.



In a large, multicenter, observational, cross-sectional study encompassing 7,911 patients in 65 countries, radiation effective dose was estimated for each examination. Patient-level best practices relating to radiation exposure were compared between genders. Analysis of covariance was used to determine any difference in radiation exposure according to gender, region, and the interaction between gender and region. Linear, logistic, and hierarchical regression models were developed to evaluate gender-based differences in radiation exposure and laboratory adherence to best practices. The study also included the United Nations Gender Inequality Index and Human Development Index as covariates in multivariable models.



The proportion of myocardial perfusion imaging studies performed in women varied among countries; however, there was no significant correlation with the Gender Inequality Index. Globally, mean effective dose for nuclear cardiology procedures was only slightly lower in women (9.6 ± 4.5 mSv) than in men (10.3 ± 4.5 mSv; p < 0.001), with a difference of only 0.3 mSv in a multivariable model adjusting for patients' age and weight. Stress-only imaging was performed more frequently in women (12.5% vs. 8.4%; p < 0.001); however, camera-based dose reduction strategies were used less frequently in women (58.6% vs. 65.5%; p < 0.001).



Despite significant worldwide variation in best practice use and radiation doses from nuclear cardiology procedures, only small differences were observed between genders worldwide. Regional variations noted in myocardial perfusion imaging use and radiation dose offer potential opportunities to address gender-related differences in delivery of nuclear cardiology care.
Air pollution and multiple acute respiratory outcomes.

Short-term effects of air pollutants on respiratory mortality and morbidity have been consistently reported but usually studied separately. To more completely assess air pollution effects, we studied hospitalisations for respiratory diseases together with out-of-hospital respiratory deaths. A time-stratified case-crossover study was carried out in six Italian cities from 2001 to 2005. Daily particulate matter (particles with a 50% cut-off aerodynamic diameter of 10 μm (PM10)) and nitrogen dioxide (NO2) associations with hospitalisations for respiratory diseases (n = 100 690), chronic obstructive pulmonary disease (COPD) (n = 38 577), lower respiratory tract infections (LRTI) among COPD patients (n = 9886) and out-of-hospital respiratory deaths (n = 5490) were estimated for residents aged ≥35 years. For an increase of 10 μg·m(-3) in PM10, we found an immediate 0.59% (lag 0-1 days) increase in hospitalisations for respiratory diseases and a 0.67% increase for COPD; the 1.91% increase in LRTI hospitalisations lasted longer (lag 0-3 days) and the 3.95% increase in respiratory mortality lasted 6 days. Effects of NO2 were stronger and lasted longer (lag 0-5 days). Age, sex and previous ischaemic heart disease acted as effect modifiers for different outcomes. Analysing multiple rather than single respiratory events shows stronger air pollution effects. The temporal relationship between the pollutant increases and hospitalisations or mortality for respiratory diseases differs.
Efficacy of a Six-Month versus a 36-Month Regimen for Prevention of Tuberculosis in HIV-Infected Persons in India: A Randomized Clinical Trial

The optimal duration of preventive therapy for tuberculosis (TB) among HIV-infected persons in TB-endemic countries is unknown.



An open-label randomized clinical trial was performed and analyzed for equivalence. Seven hundred and twelve HIV-infected, ART-naïve patients without active TB were randomized to receive either ethambutol 800 mg and isoniazid 300 mg daily for six-months (6EH) or isoniazid 300 mg daily for 36-months (36H). Drugs were dispensed fortnightly and adherence checked by home visits. Patients had chest radiograph, sputum smear and culture performed every six months, in addition to investigations if they developed symptoms. The primary endpoint was incident TB while secondary endpoints were all-cause mortality and adverse events. Survival analysis was performed on the modified intent to treat population (m-ITT) and rates compared.



Tuberculosis developed in 22 (6.4%) of 344 subjects in the 6EH arm and 13 (3.8%) of 339 subjects in the 36H arm with incidence rates of 2.4/100 py (95%CI- 1.4-3.5) and 1.6/100 py (95% CI-0.8-3.0) with an adjusted rate ratio (aIRR) of 1.6 (0.8-3.2). Among TST-positive subjects, the aIRR of 6EH was 1.7 (0.6-4.3) compared to 36H, p = 0.8. All-cause mortality and toxicity were similar in the two arms. Among 15 patients with confirmed TB, 4 isolates were resistant to isoniazid and 2 were multidrug-resistant.



Both regimens were similarly effective in preventing TB, when compared to historical incidence rates. However, there was a trend to lower TB incidence with 36H. There was no increase in isoniazid resistance compared to the expected rate in HIV-infected patients.
Quality of life in multiple sclerosis: translation in French Canadian of the MSQoL-54

Multiple Sclerosis (MS) is a neurodegenerative disease which runs its course for the remainder of the patient's life frequently causing disability of varying degrees. Negative effects on Health-related quality of life (HRQOL) are well documented and a subject of clinical study. The Multiple Sclerosis QOL 54 (MSQOL-54) questionnaire was developed to measure HRQOL in patients with MS. It is composed of 54 items, and is a combination of the SF-36 and 18 disease-specific items.



The objective of this project was to translate the MSQOL-54 into French Canadian, and to make it available to the Canadian scientific community for clinical research and clinical practice.



Across all French speaking regions, there are occurrences of variation. They include the pronunciation, sentence structure, and the lexicon, where the differences are most marked. For this reason, it was decided to translate the US original MSQOL-54 into French Canadian instead of adapting the existing French version. The SF-36 has been previously validated and published in French Canadian, therefore the translation work was performed solely on the 18 MS specific items. The translation followed an internationally accepted methodology into 3 steps: forward translation, backward translation, and patients' cognitive debriefing.



Instructions and Items 38, 43, 45 and 49 were the most debated. Problematic issues mainly resided in the field of semantics. Patients' testing (n = 5) did not reveal conceptual problems. The questionnaire was well accepted, with an average time for completion of 19 minutes.



The French Canadian MSQOL-54 is now available to the Canadian scientific community and will be a useful tool for health-care providers to assess HRQOL of patients with MS as a routine part of clinical practice. The next step in the cultural adaptation of the MSQOL-54 in French Canadian will be the evaluation of its psychometric properties.
A task-oriented circuit training in multiple sclerosis: a feasibility study

The aim of this study was to evaluate the safety, feasibility and preliminary effects of a high-intensity rehabilitative task-oriented circuit training (TOCT) in a sample of multiple sclerosis (MS) subjects on walking competency, mobility, fatigue and health-related quality of life (HRQoL).



24 MS subjects (EDSS 4.89 ± 0.54, 17 female and 7 male, 52.58 ± 11.21 years, MS duration 15.21 ± 8.68 years) have been enrolled and randomly assigned to 2 treatment groups: (i) experimental group received 10 TOCT sessions over 2 weeks (2 hours/each session) followed by a 3 months home exercise program, whereas control group did not receive any specific rehabilitation intervention. A feasibility patient-reported questionnaire was administered after TOCT. Functional outcome measures were: walking endurance (Six Minute Walk Test), gait speed (10 Meter Walk Test), mobility (Timed Up and Go test) and balance (Dynamic Gait Index). Furthermore, self-reported questionnaire of motor fatigue (Fatigue Severity Scale), walking ability (Multiple Sclerosis Walking Scale - 12) and health-related quality of life (Multiple Sclerosis Impact Scale - 29) were included. Subjects' assessments were delivered at baseline (T0), after TOCT (T1) and 3 months of home-based exercise program (T2).



After TOCT subjects reported a positive global rating on the received treatment. At 3 months, we found a 58.33% of adherence to the home-exercise program. After TOCT, walking ability and health-related quality of life were improved (p < 0.05) with minor retention after 3 months. The control group showed no significant changes in any variables.



This two weeks high-intensity task-oriented circuit class training followed by a three months home-based exercise program seems feasible and safe in MS people with moderate mobility impairments; moreover it might improve walking abilities.
Safety of primary percutaneous coronary intervention with and without (selective) thrombus aspiration.

To determine the safety and efficacy of selective thrombus aspiration during Primary Percutaneous Coronary Intervention (PCI).



This observational prospective study was conducted in the catheterization laboratory of a tertiary care cardiovascular centre. A total of 150 consecutive patients who underwent primary PCI were enrolled. Aspiration was done only when thrombus burden was considered significant. After completion of procedure angiographic and electrocardiographic signs were recorded and clinical follow up was documented up to 1 year.



No significant difference among the groups was found in age, height, weight and other risk factors like Hypertension, Diabetes Mellitus and Smoking. In general, left anterior descending artery was culprit in - 65% of patients and more than 90% of culprit vessels had visible thrombus. Multivessel disease was present in 38% of patients and 22.7% had past history of myocardial infarction. Out of 150 patients 117 (78%) underwent thrombus aspiration. No significant difference was found in ST resolution within 60 minutes (72.6 vs 81.8%; P < 0.285) and myocardial blush grade II & III (41.9 vs 27.3%; P < 0.128). No difference in event free survival was observed among the two groups (80.3 vs 84.8%; P < 0.708) at one year.



Selective thrombus aspiration in definite thrombus laden arteries and no aspiration in low or negligible thrombus burden vessels may be a safe and effective strategy in patients undergoing primary PCI. Overall poor risk profile of our patients as compared to western population necessitates further evaluation of this matter in randomized studies.
Benefits of physical exercise training on cognition and quality of life in frail older adults.

Frailty is a state of vulnerability associated with increased risks of fall, hospitalization, cognitive deficits, and psychological distress. Studies with healthy senior suggest that physical exercise can help improve cognition and quality of life. Whether frail older adults can show such benefits remains to be documented.



A total of 83 participants aged 61-89 years were assigned to an exercise-training group (3 times a week for 12 weeks) or a control group (waiting list). Frailty was determined by a complete geriatric examination using specific criteria. Pre- and post-test measures assessed physical capacity, cognitive performance, and quality of life.



Compared with controls, the intervention group showed significant improvement in physical capacity (functional capacities and physical endurance), cognitive performance (executive functions, processing speed, and working memory), and quality of life (global quality of life, leisure activities, physical capacity, social/family relationships, and physical health). Benefits were overall equivalent between frail and nonfrail participants.



Physical exercise training leads to improved cognitive functioning and psychological well-being in frail older adults.
Clinical Outcomes and Prognostic Factors of 695 Nasopharyngeal Carcinoma Patients Treated with Intensity-Modulated Radiotherapy

The 5-year clinical outcomes and prognostic factors of nasopharyngeal carcinoma (NPC) patients treated with intensity modulated radiotherapy (IMRT) were evaluated.



Six hundred ninety five NPC patients primarily treated with IMRT in Sichuan Cancer Hospital from January, 2003 to December, 2006 were analyzed retrospectively, including 540 males and 155 females. The prescription dose was delivered as follows: gross target volume (GTVnx) 67-76 Gy in 30-33 fractions, positive neck lymph nodes (GTVln-R/L) 60-70 Gy in 30-33 fractions, high-risk clinical target volume (CTV1) 60-66 Gy, low-risk clinical target volume (CTV2) 54-60 Gy, and clinical target volume of cervical lymph node regions (CTVln) 50-55 Gy.



The 5-year local control (LC), regional control, distant metastasis-free survival (DMFS), disease free survival, disease specific survival, and overall survival (OS) rates were 89.8%, 95.2%, 74.1%, 69.6%, 83.2%, and 77.1%. The 5-year DMFS of IMRT and IMRT combined with chemotherapy was 62.1% and 70.9%, the OS of them was 72.9% and 79.1%. The incidence of grade 3 acute and late toxicity was 38.3% and 4.2%, respectively.



The 5-year LC and OS rate of NPC treated with IMRT was 89.8% and 77.1%. The clinical stage, N stage, volume of GTVnx, and chemotherapy were the main prognostic factor for the OS. Distant metastasis was the main pattern of failure.