nils-herrmann/clean_scirepeval huggingface dataset:
The specific disorder of arithmetic skills. Prevalence studies in a rural and an urban population sample and their clinico-neuropsychological validation

There is an often noted lack of research in the field of disorders of arithmetic skills. The present study assessed the prevalence in both an urban and a rural population sample of German schoolchildren, using standardized academic achievement tests. Eight school classes of third graders in each area were examined (n=181, 182; respectively). We found that 6.6% (n=12) of the rural and 6.59% (n=12) of the urban school children performed significantly worse in arithmetic than in their spelling tests. Since the diagnostic criteria for the Specific disorder of arithmetical skills and their significance are widely discussed, we attempted in a second step of the study to validate the diagnosis of the Specific disorder of arithmetical skills from a neuropsychological and medical viewpoint. For the validation we assessed clinical data, imaging and neurophysiologic studies as well as a neuropsychological test battery. Nine and five of the children, respectively, were available for this further evaluation. Although the majority of these probands (n=10) had distinct arithmetic deficits, only three of them met the full diagnostic criteria of the ICD-10 for a Specific disorder of arithmetic skills. In a last step, we compared the data of both studies. Our data strongly support a thorough cliniconeurological, neuropsychological and academic assessment of students with a suspected Specific disorder of arithmetic skills. The current diagnostic criteria should be reconsidered and possibly modified towards a more psychopathologic definition. We stress the need that the condition becomes better known among all professions concerned with the care of children, as difficulties with acquiring arithmetic skills should be detected and approached appropriately as early as possible. The imperative demand of future empiric research is emphasized.
Less increase of copeptin and MR-proADM due to intervention with selenium and coenzyme Q10 combined: Results from a 4-year prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens.

Intervention with selenium and coenzyme Q10 have recently been found to reduce mortality and increase cardiac function. The mechanisms behind these effects are unclear. As selenium and coenzyme Q10 is involved in the anti-oxidative defence, the present study aimed to evaluate effects of selenium and coenzyme Q10 on copeptin and adrenomedullin as oxidative stress biomarkers. Therefore 437 elderly individuals were included and given intervention for 4 years. Clinical examination and blood samples were undertaken at start and after 18 and 48 months. Evaluations of copeptin and MR-proADM changes were performed using repeated measures of variance. Cardiovascular mortality was evaluated using a 10-year-period of follow-up, and presented in Kaplan-Meier plots. A significant increase in copeptin level could be seen in the placebo group during the intervention period (from 9.4 pmol/L to 15.3 pmol/L), compared to the active treatment group. The difference between the groups was confirmed in the repeated measurement of variance analyses (P = 0.031) with less copeptin increase in the active treatment group. Furthermore, active treatment appeared to protect against cardiovascular death both in those with high and with low copeptin levels at inclusion. Less increase of MR-proADM could also be seen during the intervention in the active treatment group compared to controls (P = 0.026). Both in those having an MR-proADM level above or below median level, significantly less cardiovascular mortality could be seen in the active treatment group (P = 0.0001, and P = 0.04 respectively). In conclusion supplementation with selenium and coenzyme Q10 during four years resulted in less concentration of both copeptin and MR-proADM. A cardioprotective effect of the supplementation was registered, irrespective of the initial levels of these biomarkers, and this protection was recognized also after 10 years of observation.
The activation of endothelin-1 pathway during methionine-induced homocysteinemia mediates endothelial dysfunction in hypertensive individuals.

Endothelin-1 (ET-1) is a key regulator of arterial blood pressure in humans, and homocysteinemia is associated with increased oxidative stress. It is still unclear whether homocysteine-induced oxidative stress is implicated in the regulation of ET-1 expression. We examined the impact of acute homocysteinemia on endothelial function in hypertensive patients and healthy individuals, and the potential role of ET-1.



In this double-blind, placebo-controlled study, 39 hypertensive and 49 healthy individuals were randomized to receive high-dose vitamins (2 g vitamin C and 800IU vitamin E) or placebo followed by methionine loading 100 mg/kg body weight. Endothelium-dependent dilation (EDD) and endothelium-independent dilation (EID) of the brachial artery were evaluated by plethysmography, at baseline and 4 h postloading (4 h PML). ET-1 was measured by ELISA, whereas total lipid hydroperoxides (per-ox) levels were measured by a commercially available photometric technique.



Acute, methionine-induced homocysteinemia decreased EDD in all study groups (P < 0.001 for all), whereas vitamins pretreatment failed to prevent this effect, despite the vitamins-induced reduction of peroxidation in the hypertensives group (P < 0.05). On the contrary, methionine loading significantly increased plasma ET-1 levels only in hypertensives (P < 0.05), an effect which was not prevented by antioxidant vitamins (P < 0.05). EID remained unchanged after methionine loading, in all study groups (P = NS for all groups).



Experimental homocysteinemia rapidly blunts endothelial function in both hypertensive individuals and healthy individuals. The rapid elevation of ET-1 levels observed only in hypertensives, suggests that ET-1 may be the key mediator of homocysteine-induced endothelial dysfunction, independently of oxidative stress.
Paired trial of cyclophosphamide and prednisone in children with nephrosis.

Tsao, Y. C., and Yeung, C. H. (1971). Archives of Disease in Childhood, 46, 327. Paired trial of cyclophosphamide and prednisone in children with nephrosis. Cyclophosphamide and prednisone were compared as the primary treatment for the nephrotic syndrome in 27 boys and 4 girls. The patients, aged between 2j and 11, were paired according to their renal histology; 19 belonged to the minimal change type, 8 to the mild proliferative type, and 4 had diffuse membranous glomerulonephritis but with selective type of proteinuria. The two groups of patients were comparable as regards period of observation before treatment, and duration of follow-up. About half the patients of each group went into spontaneous diuresis, or had no fluid retention, before treatment was started. Cyclophosphamide induced a remission more slowly than prednisone, but remission was less likely to be followed by relapse. Two patients treated with prednisone and one treated with cyclophosphamide still had persistent proteinuria at the time of review. The incidence of cyclophosphamide resistance in nephrosis remains unknown, but is probably not high. Among patients who responded to treatment, duration of persisting proteinuria varied widely, and therefore slow response must be distinguished from true resistance to treatment. Cyclophosphamide should be useful in all patients who relapse after a steroidinduced remission, but its use must be balanced against potential long-term hazards.
Risk of new primary nonbreast cancers after breast cancer treatment: a Dutch population-based study.

To assess the risk of secondary nonbreast cancers (SNBCs) in a recently treated population-based cohort of breast cancer patients focused on the association with treatment and prognostic implications.



In 58,068 Dutch patients diagnosed with invasive breast cancer between 1989 and 2003, SNBC risk was quantified using standardized incidence ratios (SIRs), cumulative incidence, and Cox regression analysis, adjusted for competing risks.



After a median follow-up of 5.4 years, 2,578 SNBCs had occurred. Compared with the Dutch female population at large, in this cohort, the SIR of SNBCs was increased (SIR, 1.22; 95% CI, 1.17 to 1.27). The absolute excess risk was 13.6 (95% CI, 9.7 to 17.6) per 10,000 person-years. SIRs were elevated for cancers of the esophagus, stomach, colon, rectum, lung, uterus, ovary, kidney, and bladder cancers, and for soft tissue sarcomas (STS), melanoma, non-Hodgkin's lymphoma, and acute myeloid leukemia (AML). The 10-year cumulative incidence of SNBCs was 5.4% (95% CI, 5.1% to 5.7%). Among patients younger than 50 years, radiotherapy was associated with an increased lung cancer risk (hazard ratio [HR] = 2.31; 95% CI, 1.15 to 4.60) and chemotherapy with decreased risk for all SNBCs (HR = 0.78; 95% CI, 0.63 to 0.98) and for colon and lung cancer. Among patients age 50 years and older, radiotherapy was associated with raised STS risk (HR = 3.43; 95% CI, 1.46 to 8.04); chemotherapy with increased risks of melanoma, uterine cancer, and AML; and hormonal therapy with all SNBCs combined (HR = 1.10; 95% CI, 1.01 to 1.21) and uterine cancer (HR = 1.78; 95% CI, 1.40 to 2.27). An SNBC worsened survival (HR = 3.98; 95%CI 3.77 to 4.20).



Breast cancer patients diagnosed in the 1990 s experienced a small but significant excess risk of developing an SNBC.
Prospective single-arm study of 72 Gy hyperfractionated radiation therapy and combination chemotherapy for anaplastic astrocytomas

Despite intensive multimodal treatment, outcome of patients with malignant glioma remains poor, and a standard dose of radiotherapy for anaplastic astrocytoma has not been defined. In the past RTOG study (83-02), the arm of 72 Gy hyperfractionated radiotherapy (HFRT) for malignant gliomas showed better outcome than the arms of higher doses (76.8 – 81.6 Gy) and the arms of lower doses (48 – 54.4 Gy). The purpose of this study is to verify the efficacy of this protocol. From July 1995, 44 consecutive eligible patients with histologically proven anaplastic astrocytoma were enrolled in this study (HFRT group). The standard regimen in this protocol was post-operative radiotherapy of 72 Gy in 60 fractions (1.2 Gy/fraction, 2 fractions/day) with concurrent chemotherapy (weekly ACNU). The primary endpoint was local control rate (LCR), and the secondary endpoints were overall survival (OS), progression-free survival (PFS) and late toxicity. Three-year OS of the HFRT group was 64.8% (95% confidence interval; 48.4–81.3%). Three-year PFS rate and LCR were 64.4% (95%CI: 48.4–80.3%) and 81.6% (95%CI: 69.2–94.8%), respectively. The number of failures at 5 years in the HFRT group were 14 (32%). The number of failures inside the irradiation field was only about half (50%) of all failures. One (2%) of the patients clinically diagnosed as brain necrosis due to radiation therapy. The results of this study suggested that 72 Gy HFRT seemed to show favorable outcome for patients with anaplastic astrocytoma with tolerable toxicity.
Accuracy of the Interpretation of Chest Radiographs for the Diagnosis of Paediatric Pneumonia

World Health Organization (WHO) radiological classification remains an important entry criterion in epidemiological studies of pneumonia in children. We report inter-observer variability in the interpretation of 169 chest radiographs in children suspected of having pneumonia.



An 18-month prospective aetiological study of pneumonia was undertaken in Northern England. Chest radiographs were performed on eligible children aged ≤16 years with clinical features of pneumonia. The initial radiology report was compared with a subsequent assessment by a consultant cardiothoracic radiologist. Chest radiographic changes were categorised according to the WHO classification.



There was significant disagreement (22%) between the first and second reports (kappa = 0.70, P<0.001), notably in those aged <5 years (26%, kappa = 0.66, P<0.001). The most frequent sources of disagreement were the reporting of patchy and perihilar changes.



This substantial inter-observer variability highlights the need for experts from different countries to create a consensus to review the radiological definition of pneumonia in children.
Pharmacokinetics of temozolomide given three times a day in pediatric and adult patients

To characterize and compare pharmacokinetic parameters in children and adults treated with temozolomide (TMZ) administered for 5 days in three doses daily, and to evaluate the possible relationship between AUC values and hematologic toxicity. TMZ pharmacokinetic parameters were characterized in pediatric and adult patients with primary central nervous system tumors treated with doses ranging from 120 to 200 mg/m2 per day, divided into three doses daily for 5 days. Plasma levels were measured over 8 h following oral administration in a fasting state. A total of 40 courses were studied in 22 children (mean age 10 years, range 3–16 years) and in 8 adults (mean age 30 years, range 19–54 years). In all patients, a linear relationship was found between systemic exposure (AUC) and increasing doses of TMZ. Time to peak concentration, elimination half-life, apparent clearance and volume of distribution were not related to TMZ dose. No differences were seen among TMZ Cmax, t1/2, Vd or CL/F in children compared with adults. Intra- and interpatient variability of systemic exposure were limited in both children and adults. No statistically significant differences were found between the AUCs of children who experienced grade 4 hematologic toxicity and children who did not. No difference appears to exist between pharmacokinetic parameters in adults and children when TMZ is administered in three doses daily. Hematologic toxicity was not related to TMZ AUC. AUC measurement does not appear to be of any use in optimizing TMZ treatment.
Maternal alcohol use and sudden infant death syndrome and infant mortality excluding SIDS.

Improvements in the rate of infant mortality (death in first year of life) have not occurred in recent years. This study investigates the association between maternal alcohol-use disorder and sudden infant death syndrome (SIDS) and infant mortality not classified as SIDS using linked, population-based health and mortality data.



Exposed mothers were identified through the presence of an International Classification of Diseases 9/10 alcohol diagnosis, a proxy for alcohol-use disorder, recorded on health, mental health, and/or drug and alcohol datasets (1983-2005). Comparison mothers without an alcohol diagnosis were frequency matched to exposed mothers on maternal age within maternal race and year of birth of their children. All offspring with their birth recorded on the Midwives Notification System compose the exposed (n = 21 841) and comparison (n = 56 054) cohorts. Cases of SIDS (n = 303) and infant mortality excluding SIDS (n = 598) were identified through linkage with the Western Australian Mortality Register. Analyses were conducted by using Cox regression and results presented as adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs).



The highest risk of SIDS occurred when a maternal alcohol diagnosis was recorded during pregnancy (aHR 6.92, 95% CI 4.02-11.90) or within 1 year postpregnancy (aHR 8.61, 95% CI 5.04-14.69). An alcohol diagnosis recorded during pregnancy more than doubled the risk of infant deaths (excluding SIDS) (aHR 2.35, 95% CI 1.45-3.83). Maternal alcohol-use disorder is attributable for at least 16.41% (95% CI 9.73%-23.69%) of SIDS and 3.40% (95% CI 2.28%-4.67%) of infant deaths not classified as SIDS.



Maternal alcohol-use disorder is a significant risk factor for SIDS and infant mortality excluding SIDS.
Micronutrient Fortification to Improve Growth and Health of Maternally HIV-Unexposed and Exposed Zambian Infants: A Randomised Controlled Trial

The period of complementary feeding, starting around 6 months of age, is a time of high risk for growth faltering and morbidity. Low micronutrient density of locally available foods is a common problem in low income countries. Children of HIV-infected women are especially vulnerable. Although antiretroviral prophylaxis can reduce breast milk HIV transmission in early infancy, there are no clear feeding guidelines for after 6 months. There is a need for acceptable, feasible, affordable, sustainable and safe (AFASS by WHO terminology) foods for both HIV-exposed and unexposed children after 6 months of age.



We conducted in Lusaka, Zambia, a randomised double-blind trial of two locally made infant foods: porridges made of flour composed of maize, beans, bambaranuts and groundnuts. One flour contained a basal and the other a rich level of micronutrient fortification. Infants (n = 743) aged 6 months were randomised to receive either regime for 12 months. The primary outcome was stunting (length-for-age Z<-2) at age 18 months. No significant differences were seen between trial arms overall in proportion stunted at 18 months (adjusted odds ratio 0.87; 95% CI 0.50, 1.53; P = 0.63), mean length-for-age Z score, or rate of hospital referral or death. Among children of HIV-infected mothers who breastfed <6 months (53% of HIV-infected mothers), the richly-fortified porridge increased length-for-age and reduced stunting (adjusted odds ratio 0.17; 95% CI 0.04, 0.84; P = 0.03). Rich fortification improved iron status at 18 months as measured by hemoglobin, ferritin and serum transferrin receptors.



In the whole study population, the rich micronutrient fortification did not reduce stunting or hospital referral but did improve iron status and reduce anemia. Importantly, in the infants of HIV-infected mothers who stopped breastfeeding before 6 months, the rich fortification improved linear growth. Provision of such fortified foods may benefit health of these high risk infants.
Comparison of one-week and two-week empirical trial with a high-dose rabeprazole in non-cardiac chest pain patients.

In patients with non-cardiac chest pain (NCCP), the optimal duration of an empirical trial with a high-dose proton pump inhibitor (PPI) is unclear. We aimed to compare the efficacy of one-week and two-week PPI trial in patients with weekly or more than weekly NCCP and to determine its optimal duration for diagnosing gastroesophageal reflux disease (GERD)-related NCCP.



Forty-two patients with at least weekly NCCP were enrolled. The baseline symptoms were assessed using a daily symptom diary for seven days. Also, esophago-gastro-duodenoscopy and 24 h esophageal pH monitoring were performed for the diagnosis of GERD. Then, patients were treated with rabeprazole 20 mg twice daily for 14 days. To assess NCCP improvement during the PPI trial, the first week and the second week symptom diary were kept for 1-7 and 8-14 days. The PPI test was considered positive if a symptom score improved (50% compared to the baseline.



There was no significant difference for a positive PPI test between GERD-related NCCP group (n = 8, 50%) and non GERD-related NCCP group (n = 6, 23%) during the first week of the PPI test. However, during the second week, GERD-related NCCP had a higher positive PPI test (n = 13, 81%) than non GERD-related NCCP (n = 7, 27%) (P = 0.001) with a sensitivity and specificity of 81% and 62%, respectively.



The rabeprazole empirical trial was diagnostic for patients with GERD-related NCCP, and its optimal duration was determined to be at least two weeks.
Phase I Study of FixedDoseRate Infusion ofGemcitabine in Patients with Unresectable Pancreatic Cancer

The purpose of this study was to determine the feasible dose of gemcitabine when administered as a fixed dose rate infusion (10 mg/m/min) on a weekly schedule to Japanese patients with unresectable advanced pancreatic cancer.  Patients were required to have histologically or cytologically proven locally advanced or metastatic pancreatic cancer for which they had received no previous chemotherapy. Gemcitabine was administered intravenously weekly for three consecutive weeks every 4weeks.Patientsat threedose levelswerescheduled to receiveescalating dosesof gemcitabine: 1000 mg/m over 100 min (Level 1), 1200 mg/m over 120 min (Level 2) and 1500 mg/m over 150 min (Level 3). A total of 16patientswereenrolled in thisstudybetweenDecember2003andSeptember 2004. Maximum-tolerated dose was not reached during the first course. Dose-limiting toxicity was Grade 4 neutropenia. Grade 3 or 4 neutropenia was observed at Level 3 in all six patients in the first course, and administration of gemcitabine on Day 8 or 15 was skipped in all six patients. Non-hematologic toxicity was mild and the most common symptoms were anorexia, nausea and vomiting. Partial response was achieved in 1 of the 17 patients (7%). Median overall survival was 7.3 months.  Gemcitabine administered at a rate of 10 mg/m/min was tolerated up to 1500 mg/m, but 1200 mg/m represented a more appropriate recommended dose in further studies owing to neutropenia in Japanese patients with advanced pancreatic cancer.
Effects of Exercise Training Intensity on Pancreatic β-Cell Function

Insulin resistance and beta-cell dysfunction both are important contributors to the pathogenesis of type 2 diabetes. Exercise training improves insulin sensitivity, but its effects on beta-cell function are less well studied.



Sedentary, overweight adults were randomized to control or one of three 8-month exercise programs: 1) low amount/moderate intensity, 2) low amount/vigorous intensity, or 3) high amount/vigorous intensity. Of 387 randomized, 260 completed the study and 237 had complete data. Insulin sensitivity (S(i)), acute insulin response to glucose (AIRg), and the disposition index (DI = S(i) x AIRg) were modeled from an intravenous glucose tolerance test.



Compared with control subjects, all three training programs led to increases in DI. However, the moderate-intensity group experienced a significantly larger increase in DI than either of the vigorous-intensity groups and through a different mechanism. The high-amount/vigorous-intensity group improved S(i) and had a compensatory reduction in AIRg, whereas the moderate-intensity group had a similar improvement in S(i) but almost no reduction in AIRg. Importantly, the inactive control group experienced a significant increase in fasting glucose.



To the extent that the DI accurately reflects beta-cell function, we observed that both moderate- and vigorous-intensity exercise training improved beta-cell function, albeit through distinct mechanisms. It is not clear which of these mechanisms is preferable for maintenance of metabolic health. While moderate-intensity exercise led to a larger improvement in DI, which may reflect a transition toward a more normal DI, longer-term investigations would be necessary to determine which was more effective at reducing diabetes risk.