nils-herrmann/clean_scirepeval huggingface dataset:
Serotonin Transporter Polymorphism Modulates N-Back Task Performance and fMRI BOLD Signal Intensity in Healthy Women

Exploring intermediate phenotypes within the human brain's functional and structural circuitry is a promising approach to explain the relative contributions of genetics, complex behaviors and neural mechanisms in the development of major depressive disorder (MDD). The polymorphic region 5-HTTLPR in the serotonin transporter gene (SLC6A4) has been shown to modulate MDD risk, but the neural underpinnings are incompletely understood.



37 right handed healthy women between 21 and 61 years of age were invited to participate in an fMRI modified n-back study. The functional polymorphism 5-HTTLPR located in the promoter region of the SLC6A4 gene was genotyped using polymerase chain reaction (PCR).



Short 5-HTTLPR allele carriers showed more blood-oxygen-level-dependent (BOLD) bilateral prefrontal cortex activation in the right [F(2, 30) = 4.8, η(2) = .25, p = .026] and left [F(2, 30) = 4.1, η(2) = .22, p = .015] inferior frontal gyrus pars triangularis with increasing n-back task difficulty relative to long 5-HTTLPR allele carriers. Short 5-HTTLPR allele carriers had inferior task performance on the most difficult n-back condition [F(2, 30) = 4.9, η(2) = .26, p = .014].



This activation pattern found in healthy at risk individuals resembles an activation pattern that is typically found in patients suffering from acute MDD. Altered function in these areas may reflect intermediate phenotypes and may help explain the increased risk of depression in short 5-HTTLPR allele carriers.
Pentoxifylline does not alter the response to inhaled grain dust.

Pentoxifylline (PTX) has been shown to reduce sepsis-induced neutrophil sequestration in the lung and inhibit endotoxin-mediated release of tumor necrosis factor-alpha (TNF-alpha). Previously, we have shown that endotoxin appears to be the principal agent in grain dust causing airway inflammation and airflow obstruction following grain dust inhalation. To determine whether PTX affects the physiologic and inflammatory events following acute grain dust inhalation, 10 healthy, nonsmoking subjects with normal airway reactivity were treated with PTX or placebo (PL) followed by corn dust extract (CDE) inhalation (0.08 mL/kg), using a single-blinded, crossover design. Subjects received PTX (1,200 mg/d) or PL for 4 days prior to CDE inhalation and 400 mg PTX or PL on the exposure day. Both respiratory symptoms and declines in FEV1 and FVC occurred following CDE exposure in both groups, but there were no significant differences in the frequency of symptoms or percent declines from baseline in the FEV1 and FVC at any of the time points measured in the study. Elevations in peripheral blood leukocyte and neutrophil concentrations and BAL total cell, neutrophil, TNF-alpha, and interleukin-8 concentrations were measured 4 h following exposure to CDE in both the PTX- and PL-treated subjects, but no significant differences were found between treatment groups. These results suggest that pretreatment with PTX prior to inhalation of CDE, in the doses used in this study, does not alter the acute physiologic or inflammatory events following exposure to inhaled CDE.
Sphincter preservation following preoperative radiotherapy for rectal cancer: report of a randomised trial comparing short-term radiotherapy vs. conventionally fractionated radiochemotherapy.

The aim was to verify whether preoperative conventionally fractionated chemoradiation offers an advantage in sphincter preservation in comparison with preoperative short-term irradiation.



Patients with resectable T3-4 rectal carcinoma without sphincters' infiltration and with a lesion accessible to digital rectal examination were randomised into: preoperative 5x5Gy short-term irradiation with subsequent total mesorectal excision (TME) performed within 7 days or chemoradiation to a total dose of 50.4Gy (1.8Gy per fraction) concomitantly with two courses of bolus 5-fluorouracil and leucovorin followed by TME after 4-6 weeks. Surgeons were obliged to base the type of operation on the tumour status at the time of surgery.



Between 1999 and 2002, 316 patients from 19 institutions were enrolled. The sphincter preservation rate was 61% in the 5x5Gy arm and 58% in the radiochemotherapy arm, P = 0.57. The tumour was on average 1.9 cm smaller (P < 0.001) among patients treated with chemoradiation compared with short-term schedule. For patients who underwent sphincter-preserving procedure, the surgeons generally followed the rule of tailoring the resection according to tumour downsizing; the median distal bowel margin was identical (2 cm) for both randomised groups. However, in the chemoradiation group, five patients underwent abdominoperineal resection despite clinical complete response.



Despite significant downsizing, chemoradiation did not result in increased sphincter preservation rate in comparison with short-term preoperative radiotherapy. The surgeons' decisions were subjective and based on pre-treatment tumour volume at least in clinical complete responders.
Bradykinin contributes to the systemic hemodynamic effects of chronic angiotensin-converting enzyme inhibition in patients with heart failure.

Bradykinin is an endogenous vasodilator that may contribute to the systemic effects of angiotensin-converting enzyme (ACE) inhibitor therapy. Using B9340, a bradykinin receptor antagonist, we determined the contribution of bradykinin to the systemic hemodynamic effects of long-term ACE inhibition in patients with chronic heart failure.



Fourteen patients with heart failure received enalapril (10 mg twice daily) or losartan (50 mg twice daily) in a randomized double-blind crossover trial. After 6 weeks treatment, patients underwent right heart catheterization and were randomized to an intravenous infusion of B9340 (2 to 20 microg/kg per minute) or saline placebo. After B9340 infusion in patients treated with enalapril, mean arterial pressure (+5.2 mm Hg), systemic vascular resistance (+315 dynes x s/cm5), pulmonary arterial wedge pressure (-1.4 mm Hg), and mean pulmonary arterial pressure (-1.3 mm Hg) were greater compared with losartan (P<0.005, P=0.07, P<0.0001, and P<0.05 respectively) or placebo infusion (P< or =0.005 for all). There was a reduction in cardiac output after B9340 with enalapril compared with placebo (P<0.001) but not losartan.



Bradykinin contributes to the systemic hemodynamic effects of long-term ACE inhibition in patients with heart failure. This mechanism may explain the apparent clinical differences between ACE inhibitors and angiotensin receptor blockers in the treatment of heart failure.
Effect of meal timing and glycaemic index on glucose control and insulin secretion in healthy volunteers.

Shiftworkers have a higher risk of CHD and type 2 diabetes. They consume a large proportion of their daily energy and carbohydrate intake in the late evening or night-time, a factor which could be linked to their increase in disease risk. We compared the metabolic effects of varying both dietary glycaemic index (GI) and the time at which most daily energy intake was consumed. We hypothesised that glucose control would be optimal with a low-GI diet, consumed predominantly early in the day. A total of six healthy lean volunteers consumed isoenergetic meals on four occasions, comprising either high- or low-GI foods, with 60 % energy consumed predominantly early (breakfast) or late (supper). Interstitial glucose was measured continuously for 20 h. Insulin, TAG and non-esterified fatty acids were measured for 2 h following every meal. Highest glucose values were observed when large 5021 kJ (1200 kcal) high-GI suppers were consumed. Glucose levels were also significantly higher in predominantly late high- v. low-GI meals (P<0·01). Using an estimate of postprandial insulin sensitivity throughout the day, we demonstrate that this follows the same trend, with insulin sensitivity being significantly worse in high energy consumed in the evening meal pattern. Both meal timing and GI affected glucose tolerance and insulin secretion. Avoidance of large, high-GI meals in the evening may be particularly beneficial in improving postprandial glucose profiles and may play a role in reducing the risk of type 2 diabetes; however, longer-term studies are needed to confirm this.
Efficacy and Treatment Costs of Monotherapy with bDMARDs in the Treatment of Rheumatoid Arthritis in Patients Intolerant to or Inappropriate to Continue Treatment with Methotrexate

Only limited information is available on cost efficacy of the various biological agents used to treat patients with rheumatoid arthritis with intolerance or for whom it would be inappropriate to continue treatment with conventional agents. We estimated the efficacy and treatment costs of monotherapy with biological agents in the treatment of this group of patients.



Data from two previous meta-analyses in the treatment of patients who are intolerant to methotrexate (MTX), or for whom it would be inappropriate to continue treatment with MTX was used. Pharmacoeconomic comparison between biological agents was carried out to estimate the respective cost for the number needed to treat (NNT) compared to placebo using both American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) criteria. The analysis involved the four agents approved in Italy: adalimumab (ADA), etanercept (ETN), certolizumab pegol (CTZ), and tocilizumab (TCZ). A six-month period was considered sufficient to understand the most important differences in efficacy and treatment costs. Direct medical costs, including pharmacological therapy, administration and monitoring were considered.



Using both ACR and EULAR criteria, TCZ (intravenous [iv]/subcutaneous [sc]) had a lower NNT than the other agents. The difference in NNT observed for ETN was more pronounced with EULAR criteria, whereas in the comparison with ADA, the most sensitive differences were observed with ACR criteria. ETN had the lowest treatment cost (€6402.19), followed by ADA (€6698.84), TCZ sc (€6887.61), and TCZ iv (€7130.83). TCZ sc had the lowest cost for NNT with both ACR and EULAR criteria. The differences compared to ETN and ADA were significant and related with the level of efficacy. Sensitivity analysis confirmed these results.



TCZ is a cost-effective therapeutic option compared to other tumor necrosis factor-α inhibitors (ADA, ETA, CTZ) as first-line monotherapy for patients who are intolerant to MTX, or for whom it is inappropriate to continue treatment with MTX.
Are changes in mortality from stroke caused by changes in stroke event rates or case fatality? Results from the WHO MONICA Project.

Mortality from stroke has been declining over recent decades in most countries, except in Eastern Europe. In this analysis, based on the World Health Organization Monitoring Trends and Determinants in Cardiovascular Disease (WHO MONICA) Project, we explored to what extent these trends are due to changes in stroke event rate and to changes in case fatality.



The WHO MONICA Project collected standardized data from 14 populations in 9 countries. All acute strokes occurring in men and women 35 to 64 years of age were included. Registration was carried out between 1982 and 1995, resulting in time spans from 7 to 13 years. Trends in event rates and case fatality were calculated as average annual percentage change.



Up to 6-fold differences were observed in stroke mortality. Mortality declined in 8 of 14 populations in men and in 10 of 14 populations in women. An increase in mortality was observed in Eastern Europe. In the populations with a declining trend, about two thirds of the change could be attributed to a decline in case fatality. In populations with increasing mortality, the rise was explained by an increase in case fatality.



In most populations, changes in stroke mortality, whether declining or increasing, were principally attributable to changes in case fatality rather than changes in event rates. Whether this was due to changes in the management of stroke or changes in disease severity cannot be established on the basis of these results.
A prospective study of glycaemic status in anti-psychotic-treated patients.

Anti-psychotic drugs, particularly the second generation, or ;atypical' agents, have been implicated in the development of metabolic dysfunction such as diabetes mellitus. There is a paucity of longitudinal data on the natural history of glucose homeostasis in anti-psychotic-treated patients, and there are no universally accepted strategies for managing worsening glycaemic control in this population. Notwithstanding, several guidelines recommend switching to a ;lower risk' agent if patients develop worsening glycaemic control during anti-psychotic treatment. We prospectively followed a cohort of 106 anti-psychotic-treated patients from across the diagnostic spectrum, and investigated changes in glycaemic status. Between baseline and follow-up assessment (mean follow-up time, 599.3 [SD+/-235.4] days glycaemic status was unchanged in 78 (86.7%) patients; 5 (5.6%) reverted from impaired fasting glucose (IFG) to normoglycaemia in the absence of any pharmacological or lifestyle intervention and all were taking a ;high risk' drug (clozapine or olanzapine). These preliminary data suggest that progression to overt diabetes mellitus is not inevitable in patients who develop IFG during anti-psychotic treatment. Switching to another agent simply on the basis of the development of IFG may not offer any advantage, especially if the mental state is stable.
Relationships between balance control and cognitive functions, gait speed, and activities of daily living

The purpose of this study was to examine the relationship between balance control and cognitive functions, gait speed, and activities of daily living. In all, 80 elderly participants with mild cognitive impairment (mean age 67.07 ± 4.3 years) were randomly allocated into the experimental group (n = 40) or the control group (n = 40). Balance control was evaluated by the Balance Evaluation Systems Test (BESTest). Cognitive functions were evaluated by the Trail Making Test and the Nine Hole Peg Test. Gait speed was assessed by the Up and Go test with and without dual task. For evaluation of activities of daily living (ADL), the BADLS test was used. The experimental group underwent CogniPlus 20 training sessions twice a week. Both groups had 30 min of physical training daily for 10 weeks. After training, there were five significant correlations found in the experimental group (balance control and visuomotor coordination, psychomotor speed, gait speed with and without cognitive tasks, and activities of daily living). In the control group, one significant correlation was found between balance control and gait speed. The cognitive-motor training performed for 10 weeks confirmed more significant relationships between balance control, cognitive functions, gait speed, and activities of daily living, when compared with motor intervention alone. Ziel dieser Studie war es, die Beziehung zwischen der Kontrolle des Körpergleichgewichts und den kognitiven Funktionen, der Gehgeschwindigkeit sowie den Aktivitäten des täglichen Lebens zu untersuchen. Insgesamt 80 ältere Menschen mit leichter kognitiver Beeinträchtigung (Durchschnittsalter 67,07 ± 4,3 Jahre) wurden randomisiert und der Versuchsgruppe (n = 40) oder Kontrollgruppe (n = 40) zugeteilt. Die Kontrolle des Körpergleichgewichts wurde mit dem Balance Evaluation Systems Test (BESTest) bewertet.  Funktionen wurden mit dem Trail Making Test und dem Nine Hole Peg Test eingeschätzt. Die Gehgeschwindigkeit wurde im Timed-Up-and-Go-Test mit oder ohne doppelte Aufgabenstellung ermittelt. Für die Bewertung der Aktivitäten des täglichen Lebens wurde der BADLS-Test angewendet. Die Versuchsgruppe durchlief 2-mal wöchentlich CogniPlus-20-Trainingseinheiten. Beide Gruppen absolvierten über 10 Wochen täglich ein 30-minütiges körperliches Training. Nach Beendigung des Trainings wurden 5 signifikante Korrelationen in der Versuchsgruppe festgestellt (Kontrolle des Körpergleichgewichts und visuomotorische Koordination, psychomotorische Geschwindigkeit, Gehgeschwindigkeit mit und ohne kognitive Aufgaben sowie Aktivitäten des täglichen Lebens). In der Kontrollgruppe fand sich nur eine signifikante Korrelation zwischen der Kontrolle des Körpergleichgewichts und der Gehgeschwindigkeit. Das kognitiv-motorische Training über 10 Wochen bestätigte im Vergleich zur alleinigen motorischen Intervention mehr signifikante Beziehungen zwischen der Kontrolle des Körpergleichgewichts und den kognitiven Funktionen, der Gehgeschwindigkeit und den Aktivitäten des täglichen Lebens.
Effectiveness of a community based low intensity exercise program for older adults.

The aim of this study was to assess the effectiveness of a community-based, low-intensity exercise programme in older adults from socio-economically and historically disadvantaged communities.



Three community centres were selected: two were allocated to the same 20-week, twice-weekly exercise program (EX1, n=38; EX2, n=32); and a third to relaxation classes (control/CTL; n=21). Measurements at baseline, 10 and 20 weeks included field tests for anthropometry, static and dynamic balance, gait, upper and lower body strength, 6-minute walk test, blood pressure, activities of daily living (ADL), instrumental activities of daily living (IADL), physical activity recall and self perceived health status.



Exercise training significantly improved dynamic balance in both groups (75.1+/-31.5 vs 55.3+/-13.6 s, and 53.3+/-17.0 vs 37.0+/-10.4 s, for EX1 and EX2, respectively, p < 0.001 compared to CTL (57+/-27 vs 53+/-15 s). Lower body strength, as measured by the number of sit-to-stand repetitions in 10 s was also significantly improved in both EX1 and EX2 (p<0.001). No significant changes occurred in the CTL group. Systolic blood pressure decreased in both EX1 and EX2 from baseline to 20 weeks (147.8+/-12.8 vs 143.9+/-3.3 mmHg and 143.0+/-13.9 vs 137.4+/-14.5 mmHg, respectively, p<0.009, compared to CTL (147+/-13 to 150+/-16 mmHg). Furthermore, in a sub sample of subjects who were hypertensive at the outset, exercise intervention was associated with a significant decrease in systolic blood pressure (n=26; 146+/-14 mmHg to 140+/-14 mmHg; p=0.005). Variables unaffected by exercise training were upper body strength, body composition and fat distribution, 20 m walk, cardiovascular endurance, time spent in recreational activities, self perceived health status and ADL.



A community-based, low intensity exercise programme improved dynamic balance and lower body strength in community dwelling older adults and improved blood pressure, particularly in those who were hypertensive.
Case-control study of diet and prostate cancer in China

A higher incidence of prostate cancer is observed in the Western world than in Asian countries. Although it is relatively rare in China, an increased incidence has been reported in recent years. Studies in high-risk populations have suggested that dietary fat may play a role in enhancing the risk of developing prostate cancer. However, limited epidemiologic study has never examined the role of diet in low risk populations.  A case-control study was conducted in 12 cities in China to evaluate the relationship between dietary factors and prostate cancer risk. We conducted personal interviews with 133 histopathologically confirmed prostate cancer cases diagnosed between 1989 to 1992 and 265 neighborhood controls of similar age.  Cases were more likely than controls to consume food with high fat and from animal sources (p<0.01). The daily fat intake and the percentage of energy from fat were statistically significantly higher among cases than among controls (p<0.01). The adjusted odds ratio for total fat between lowest quartiles and highest quartiles was OR=3.6 (95percent C.I. 1.8-7.2); for saturated fat, OR=2.9 (95percent C.I. 1.5- 5.7); and for unsaturated fat, OR=3.3 (95percent C.I. 1.7- 6.3).  The data suggest that dietary fat, both saturated and unsaturated, are associated with an increased risk for prostate cancer in a low risk population.
A phase I study of doxifluridine combined with weekly paclitaxel for metastatic gastric cancer

Based on the synergistic effect in preclinical studies, a phase I clinical trial for the combination of paclitaxel and doxifluridine (an intermetabolite of capecitabine) was performed to determine the recommended dose for the treatment of patients with metastatic gastric cancer. The dose of paclitaxel was increased from 60 mg/m2 at level 1 to 90 mg/m2 at level 5. It was administered as a 1-h infusion on days 1 and 8. The dose of doxifluridine was fixed at 600 mg/m2 per day up to level 3, and escalated to 800 mg/m2 per day at levels 4 and 5. It was administered orally for 2 weeks. The treatment was repeated every 3 weeks. A total of 28 patients were enrolled. No dose-limiting toxicity (DLT) was observed at levels 1 and 2 (paclitaxel 70 mg/m2). A DLT of grade 4 neutropenia lasting for more than 4 days was observed in one patient at level 3 (paclitaxel 80 mg/m2). In addition, the first five of six patients in this group experienced grade 3 neutropenia during the first treatment cycle. A further six patients were added in order to confirm the safety of this dosage level, and no more DLTs except for grade 3 nausea in one patient were observed in the second cohort. No DLT was seen in three patients at level 4 (paclitaxel 80 mg/m2). DLTs (grade 3 neuropathy in one patient and a treatment delay of the second cycle for more than 1 week due to grade 3 neutropenia in another) were observed in two out of six patients at level 5 (paclitaxel 90 mg/m2), and this dose level was determined as the maximum tolerated dose. The tumor response rate was 42% (95% confidence interval 20–67%) in 19 patients with measurable lesions. The recommended dose was determined as 80 mg/m2 of paclitaxel (days 1 and 8) and 800 mg/m2 of doxifluridine (days 1–14) every 3 weeks. The results of this phase I study are encouraging and a phase II trial is thus warranted.
Comparison of PY 108-068, a new calcium antagonist, with nifedipine in exercise-induced asthma.

Several calcium antagonists, each with significantly different chemical structures, have demonstrated variable attenuation of exercise-induced asthma. Quantitative comparisons have been hampered by differences in the intensity of challenge and the severity of the underlying disease between groups of patients. In 12 asthmatic adults with relatively severe exercise-induced asthma, we compared the effect of a new calcium antagonist, PY 108-068, in doses of 75 mg and 150 mg with nifedipine (30 mg) and placebo on resting flow rates and flow rates after exercise. Over a three-week period, each patient completed a four-day, randomized, double-blind Latin-square study. After receiving one of four oral drugs, spirometry was repeated every 30 minutes for two hours, followed by a six-minute treadmill exercise test breathing dry air. The exercise tests were well matched for work rate, ventilation, heart rate, and oxygen uptake. Spirometry was then repeated seven times over the next 30 minutes after exercise. Though both 150 mg of PY 108-068 and nifedipine were associated with mild bronchodilation before exercise, only the latter was significant (p less than 0.05). Exercise-induced asthma (expressed as maximal percent fall in the forced expiratory volume in one second from before baseline) was significantly attenuated only by 150 mg of PY 108-068 compared to placebo (24 +/- 13 vs 40 +/- 16; p less than 0.05). Headache, which occurred in six subjects after nifedipine, five after 150 mg of PY 108-068, one after 75 mg of PY 108-068, and none after placebo, was subjectively more severe after nifedipine. We conclude that in these patients, there was a tendency for mild bronchodilation before exercise with both 150 mg of PY 108-068 and nifedipine, but only the 150-mg dose provided significant protection against exercise-induced asthma two hours after the drug.