nils-herrmann/clean_scirepeval huggingface dataset:
Vorkommen einer p16INK4a-Expression in Zytologien der Harnblase

In Harnblasenspülflüssigkeiten sollte die Expression des Tumorsuppressorgens p16INK4a immunzytochemisch untersucht und im Vergleich mit dem histologischen Ergebnis die Sensitivität und die Spezifität errechnet werden, ob Urothelkarzinome der Harnblase erkannt werden können. Es wurden 82 Sedimente von Patienten mit dem Verdacht auf ein Urothelkarzinom auf p16INK4a untersucht. Bei 46 Patienten bestand ein Karzinom, das 29-mal durch eine Expression von p16INK4a erkannt wurde. In 36 Fällen ohne Malignität fand sich 30-mal keine p16INK4a-Expression. Insgesamt zeigte sich eine Sensitivität von 63% und eine Spezifität von 83%. Während gut differenzierte Urothelkarzinome kaum erkannt wurden (Sensitivität 27%), konnten mittelgradig (Sensitivität 69%) und entdifferenzierte Karzinome (Sensitivität 77%) gut erkannt werden. Verglichen mit den bekannten, minimal-invasiven Tumormarkern (z. B. NMP22) scheint der Nachweis einer Expression von p16INK4a ein spezifisches und insbesondere bei entdifferenzierten Tumoren ein sensitives Verfahren zu sein, um Urothelkarzinome erkennen zu können. Insbesondere die hohe Spezifität ermutigt das Verfahren im Hinblick auf ein Tumorscreening weiter zu untersuchen. This study was carried out to learn whether cytological specimens from urinary bladder lavages express the tumor suppressor gene p16INK4a, whether an abnormally increased expression indicates a cancerous state and whether cytological measurements are comparable regarding sensitivity and specificity with measurements made in histological sections of biopsies. A total of 82 urine specimens of patients suspected of having a bladder tumor were examined for the presence of p16INK4a. Out of 46 patients with urothelial carcinoma 29 expressed p16INK4a in the cells in the urine specimens. Out of 36 patients free of cancer 30 expressed no p16INK4a in cytological specimens. The sensitivity of the expression proved to be 63% and the specificity 83%. Well-differentiated carcinomas seldomly expressed an increased p16INK4a (sensitivity 27%), whereas moderately differentiated carcinomas showed a sensitivity of 69% and poorly differentiated carcinomas a sensitivity of 77%. Compared to other minimally invasive tumor markers, such as NMP22, the expression of p16INK4a in cytology specimens of urine appears to be a sensitive marker for urothelial carcinoma, especially for the detection of poorly differentiated carcinomas. Its high specificity makes it ideal for use in tumor screening.
Ability of Serum Glial Fibrillary Acidic Protein, Ubiquitin C-Terminal Hydrolase-L1, and S100B To Differentiate Normal and Abnormal Head Computed Tomography Findings in Patients with Suspected Mild or Moderate Traumatic Brain Injury

Head computed tomography (CT) imaging is still a commonly obtained diagnostic test for patients with minor head injury despite availability of clinical decision rules to guide imaging use and recommendations to reduce radiation exposure resulting from unnecessary imaging. This prospective multicenter observational study of 251 patients with suspected mild to moderate traumatic brain injury (TBI) evaluated three serum biomarkers' (glial fibrillary acidic protein [GFAP], ubiquitin C-terminal hydrolase-L1 [UCH-L1] and S100B measured within 6 h of injury) ability to differentiate CT negative and CT positive findings. Of the 251 patients, 60.2% were male and 225 (89.6%) had a presenting Glasgow Coma Scale score of 15. A positive head CT (intracranial injury) was found in 36 (14.3%). UCH-L1 was 100% sensitive and 39% specific at a cutoff value >40 pg/mL. To retain 100% sensitivity, GFAP was 0% specific (cutoff value 0 pg/mL) and S100B had a specificity of only 2% (cutoff value 30 pg/mL). All three biomarkers had similar values for areas under the receiver operator characteristic curve: 0.79 (95% confidence interval; 0.70-0.88) for GFAP, 0.80 (0.71-0.89) for UCH-L1, and 0.75 (0.65-0.85) for S100B. Neither GFAP nor UCH-L1 curve values differed significantly from S100B (p = 0.21 and p = 0.77, respectively). In our patient cohort, UCH-L1 outperformed GFAP and S100B when the goal was to reduce CT use without sacrificing sensitivity. UCH-L1 values <40 pg/mL could potentially have aided in eliminating 83 of the 215 negative CT scans. These results require replication in other studies before the test is used in actual clinical practice.
Phase I study of tanespimycin in combination with bortezomib in patients with advanced solid malignancies

To determine the maximum tolerated dose (MTD) and characterize the dose-limiting toxicities (DLT) of tanespimycin when given in combination with bortezomib. Experimental design Phase I dose-escalating trial using a standard cohort “3+3” design performed in patients with advanced solid tumors. Patients were given tanespimycin and bortezomib twice weekly for 2 weeks in a 3 week cycle (days 1, 4, 8, 11 every 21 days).  Seventeen patients were enrolled in this study, fifteen were evaluable for toxicity, and nine patients were evaluable for tumor response. The MTD was 250 mg/m2 of tanespimycin and 1.0 mg/m2 of bortezomib when used in combination. DLTs of abdominal pain (13 %), complete atrioventricular block (7 %), fatigue (7 %), encephalopathy (7 %), anorexia (7 %), hyponatremia (7 %), hypoxia (7 %), and acidosis (7 %) were observed. There were no objective responses. One patient had stable disease.  The recommended phase II dose for twice weekly 17-AAG and PS341 are 250 mg/m2 and 1.0 mg/m2, respectively, on days 1, 4, 8 and 11 of a 21 day cycle.
The Influence of Hostility and Family History of Cardiovascular Disease on Autonomic Activation in Response to Controllable versus Noncontrollable Stress, Anger Imagery Induction, and Relaxation Imagery

Autonomic activation in response to controllable versus noncontrollable stress, anger imagery induction, and relaxation imagery was studied among 80 participants between the ages of 18 and 34 years. Participants differed in level of trait hostility and family history of cardiovascular disease. Results were obtained through power spectral analyses of electrocardiograph R-R intervals, which produced an index of autonomic nervous system activation. For both male and female populations, parasympathetic regulation was diminished during anger induction for individuals with high levels of trait hostility and having a family history of cardiovascular disease. Similar results were obtained for women during the uncontrolled stress condition. Based on family history of cardiovascular disease and trait hostility, men responded differentially to relaxation imagery induction, whereas no differences were found among females.
Effects of continuous passive motion on reversing the adapted spinal circuit in humans with chronic spinal cord injury.

To investigate the possibility of restoring the adapted spinal circuit after spinal cord injury (SCI) by means of long-term continuous passive motion (CPM) of the ankle joint.



Randomized controlled trial with repeated measures.



Research laboratory in a general hospital.



Individuals with motor complete SCI (N=14) were recruited from a community.



CPM of the ankle joint for 1 hour a day, 5 days a week for 4 weeks.



Modified Ashworth Scale (MAS) scores for evaluation of spasticity and postactivation depression (PAD) were documented prior to and after intervention.



MAS scores improved after 4 weeks of CPM intervention, indicating a reduction in spasticity of the ankle joint. PAD was restored after 4 weeks of training.



Passive motion of the ankle joint alone was sufficient in reversing the adapted spinal circuit, and therefore indicates that spasticity after SCI could possibly be managed by CPM intervention. The results of this study support the use of the passive mode of robot-assisted therapy for humans with complete SCI who cannot exercise actively.
Usefulness of N-terminal pro-B-type natriuretic peptide increase with exercise for predicting cardiovascular mortality in patients with heart failure.

N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) level at rest is related to left ventricular (LV) function and cardiovascular mortality in patients with heart failure (HF). There are limited and controversial data regarding changes in NT-pro-BNP level during exercise in patients with HF. The aim of this study was to investigate the effects of exercise on NT-pro-BNP levels and the relation between increases in NT-pro-BNP and the LV ejection fraction and cardiovascular mortality in patients with HF. Seventy-five patients with HF (New York Heart Association classes I to III) and 20 healthy subjects were enrolled in the study. Echocardiographic examination was performed. The modified Bruce protocol was used for symptom-limited exercise testing. Levels of NT-pro-BNP were measured at rest and after peak exercise. The patients were followed up for 690 to 840 days for cardiovascular mortality. Exercise induced significant increases in NT-pro-BNP in patients and controls. Except for a relative increase in NT-pro-BNP during exercise (relative DeltaNT-pro-BNP), NT-pro-BNP concentrations at rest and during peak exercise and absolute increases in NT-pro-BNP during exercise (absolute DeltaNT-pro-BNP) were significantly higher in patients with HF (p <0.001). Absolute DeltaNT-pro-BNP was positively correlated with NT-pro-BNP at rest (p <0.001). The level of absolute DeltaNT-pro-BNP was the most important parameter in predicting a LV ejection fraction <30% (p <0.001). Absolute DeltaNT-pro-BNP and LV end-systolic volume were found to be independent predictors of mortality (p = 0.012 and p = 0.015, respectively). In conclusion, exercise induced increases in NT-pro-BNP in patients and healthy subjects. Absolute increase in NT-pro-BNP is a reliable parameter in predicting a low LV ejection fraction and may help in the identification of patients at high risk for mortality.
Cigarette smoking and lung cancer: modeling total exposure and intensity.

Investigators typically analyze cigarette smoking using smoking duration and intensity (number of cigarettes smoked per day) as risk factors. However, odds ratios (OR) for categories of intensity either adjusted for, or jointly with, duration of smoking may be distorted by differences in total pack-years of exposure to cigarette smoke. To study effects of intensity, we apply a linear excess OR model to compare total exposure delivered at low intensity for a long period of time with an equal total exposure delivered at high intensity for a short period of time to data from a large case-control study of lung cancer. The excess OR per pack-year increases with intensity for subjects who smoke < or =20 cigarettes per day and decreases with intensity for subjects who smoke >20 cigarettes per day. The intensity patterns are homogeneous by histologic type of lung cancer, suggesting that observed differences in risks by histologic type are related to total smoking exposure or smoking duration and not smoking intensity. At lower smoking intensities, there is an "exposure enhancement" effect such that for equal total exposure, the excess OR per pack-year increases with intensity. At higher smoking intensities, there is a "reduced potency" or "wasted exposure" effect such that for equal total exposure, the excess OR per pack-year decreases with intensity (i.e., smoking at a lower intensity for longer duration is more deleterious than smoking at a higher intensity for shorter duration).
Structure-based 3D QSAR and design of novel acetylcholinesterase inhibitors

The paper describes the construction, validation and application of a structure-based 3D QSAR model of novel acetylcholinesterase (AChE) inhibitors. Initial use was made of four X-ray structures of AChE complexed with small, non-specific inhibitors to create a model of the binding of recently developed aminopyridazine derivatives. Combined automated and manual docking methods were applied to dock the co-crystallized inhibitors into the binding pocket. Validation of the modelling process was achieved by comparing the predicted enzyme-bound conformation with the known conformation in the X-ray structure. The successful prediction of the binding conformation of the known inhibitors gave confidence that we could use our model to evaluate the binding conformation of the aminopyridazine compounds. The alignment of 42 aminopyridazine compounds derived by the docking procedure was taken as the basis for a 3D QSAR analysis applying the GRID/GOLPE method. A model of high quality was obtained using the GRID water probe, as confirmed by the cross-validation method (q2LOO = 0.937, q2L50%O = 0.910). The validated model, together with the information obtained from the calculated AChE-inhibitor complexes, were considered for the design of novel compounds. Seven designed inhibitors which were synthesized and tested were shown to be highly active. After performing our modelling study the X-ray structure of AChE complexed with donepezil, an inhibitor structurally related to the developed aminopyirdazines, has been made available. The good agreement found between the predicted binding conformation of the aminopyridazines and the one observed for donepezil in the crystal structure further supports our developed model.
Association between adiposity and cognitive function in young men: Hormonal mechanisms.

To determine the association between adiposity, hormones, and cognition in young men with abdominal obesity.



In this cross-sectional observational study, 53 nondiabetic men with abdominal obesity (mean body mass index, 37.3 kg/m(2) ; age, 22-45 years) and normal intelligence underwent detailed measures of body composition, hormonal profiles, and cognition. Age- and education-adjusted performance in five cognitive domains was examined.



Total fat percentage was negatively associated with visuospatial skills (P = 0.002) and visual memory (P = 0.012). Insulin resistance (homeostatic model assessment of insulin resistance) was also negatively associated with these domains (P = 0.05 and trend, P = 0.06, respectively). Total testosterone levels were negatively associated with executive function and verbal learning and memory (P = 0.04 for each), but free testosterone was not. Sex hormone-binding globulin (SHBG) was also inversely associated with performance in these domains (P = 0.015 and trend, P = 0.09, respectively). In a stepwise regression model including percentage fat, homeostatic model assessment of insulin resistance, SHBG, and free testosterone, SHBG was the only variable selected for executive function (P = 0.05) and showed a trend for verbal learning and memory (P = 0.09).



Adiposity and insulin resistance were associated with worse function in visual domains. An unexpected negative association is reported between SHBG and cognitive measures, which seemed to be independent of free testosterone levels.
Weight loss due to a very low calorie diet differentially affects insulin sensitivity and interleukin-6 serum levels in nondiabetic obese human subjects.

Inflammatory mechanisms are involved in the pathogenesis of type 2 diabetes with interleukin (IL)-6 being particularly important. While long term exercise has been shown to be associated with reduction in IL-6 serum levels in several reports, the discussion on the effect of dietary intervention on IL-6 serum levels is controversial. In the present study, we aimed to investigate the effect of weight loss due to a very low calorie diet (VLCD) on insulin sensitivity and IL-6 serum levels in nondiabetic obese human individuals. 10 patients with obesity were examined during 12 weeks of a VLCD (800 kcal/d). Body composition was measured by impedance analysis. Blood samples were taken before, during, and after the dietary intervention. Leptin, adiponectin, and IL-6 serum levels were measured by ELISA. The body weight decreased significantly from 123.9±6.2-103.5±5.6 kg with a significant reduction in body fat content (43.2±2.3-36.1±3.1%). Leptin levels exhibited a significant decrease from 56.8±5.6-27.9±5.6 ng/ml while adiponectin levels increased significantly from 7.5±0.9-10.6±1.1 μg/ml. Thereby the leptin-to-adiponectin ratio, a novel marker for insulin sensitivity, significantly improved. Mean IL-6 serum concentrations were within the normal range (3.2±0.8 pg/ml) before the study and were not significantly altered by the nutritional therapy. Despite improvement of insulin sensitivity, IL-6 serum levels did not change throughout the study period, suggesting that in nondiabetic obese human subjects IL-6 might have only a minor role in the impairment of insulin sensitivity.
Long-term nutrition intervention following major upper gastrointestinal surgery: a prospective randomized controlled trial

Nutritional status has been shown to affect quality of life, tolerance of future treatments and survival in people having undergone major upper gastrointestinal surgery. The objective of this trial was to assess the impact of intense individualized dietary advice following major upper gastrointestinal surgery on nutritional status, dietary intake, gastrointestinal symptoms and quality of life, compared to the current usual care.On discharge from hospital, people having had major upper gastrointestinal surgery were randomized to have dietetic follow-up fortnightly for 6 months or to a control group. Data collection was conducted at baseline, and at 1, 3 and 6 months.Twenty-seven people were randomized to either the intervention or control group. There was a small but non-significant difference in percent weight loss in the intervention (−0.8±8.8) compared to the control group (−2.7±9.7) at 6 months. There were no other differences between the two groups.This small study did not demonstrate that intense individualized dietary advice leads to improvements in nutritional status and quality of life for people having had major upper gastrointestinal surgery. The study does highlight that this group is at high nutritional risk, and does support the need for a larger multicentre study.
Garlic powder and plasma lipids and lipoproteins: a multicenter, randomized, placebo-controlled trial.

Garlic powder tablets have been reported to lower serum cholesterol levels. There is widespread belief among the general public that garlic powder tablets aid in controlling cholesterol levels. However, much of the prior data demonstrating the cholesterol-lowering effect of garlic tablets involved studies that were inadequately controlled.



To determine the lipid-lowering effect of garlic powder tablets in patients with hypercholesterolemia.



This was a randomized, double-blind, placebo-controlled, 12-week, parallel treatment study carried out in 2 outpatient lipid clinics. Entry into the study after 8 weeks of diet stabilization required a mean low-density lipoprotein cholesterol level on 2 visits of 4.1 mmol/L (160 mg/dL) or lower and a triglyceride level of 4.0 mmol/L (350 mg/dL) or lower. The active treatment arm received tablets containing 300 mg of garlic powder (Kwai) 3 times per day, given with meals (total, 900 mg/d). This is equivalent to approximately 2.7 g or approximately 1 clove of fresh garlic per day. The placebo arm received an identical-looking tablet, also given 3 times per day with meals. The main outcome measures included levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol after 12 weeks of treatment.



Twenty-eight patients (43% male; mean +/- SD age, 58 +/- 14 years) received garlic powder treatment and 22 (68% male; mean +/- SD age, 57 +/- 13 years) received placebo treatment. There were no significant lipid or lipoprotein changes in either the placebo- or garlic-treated groups and no significant difference between changes in the placebo-treated group compared with changes in the garlic-treated patients.



Garlic powder (900 mg/d) treatment for 12 weeks was ineffective in lowering cholesterol levels in patients with hypercholesterolemia.
Conservative treatment in patients sick-listed for acute low-back pain: a prospective randomised study with 12 months’ follow-up

We evaluated three different conservative treatment methods for acute low-back pain patients in groups following a manual therapy programme, an intensive training programme, or a general practitioner programme, the latter serving as the control group. Patients aged 19–64 years on sick leave for low-back pain with or without sciatica were included in a prospective randomised study evaluating outcomes such as impairment, pain, functional disability, socio-economic disability and satisfaction with the treatment or explanations. Evaluation by unbiased observers was performed at 1, 3 and 12 months. The three treatment groups were comparable at baseline. With regard to satisfaction, the patients in the manual therapy programme and those in the intensive training programme were more satisfied with the treatment than those in the general practitioner programme at all follow-ups. With regard to the explanations of current low-back pain episodes, the patients in the manual therapy programme were more satisfied than those in the general practitioner programme at all follow-ups. The manual therapy programme group were also more satisfied with the explanations than those in the intensive training programme at the 1-month follow-up. However, no differences were revealed between the groups with respect to outcomes on measures of impairment, pain, functional disability or socio-economic disability. All three study groups showed rapid improvement. After 1 month a significant improvement was noted in all outcome values compared with the values on entry to the study. Within the limitations discussed in our study, it is concluded that (1) patients sick listed with acute low-back pain, with or without sciatica, will be significantly improved after 1 month regardless of conservative treatment programme; (2) they will be more satisfied with the treatment if they are referred to a manual treatment programme or a training treatment programme; (3) they will be more satisfied with the explanations of the acute low-back problem if they are referred to one of the above groups, especially the manual treatment group; (4) they will not show any other differences with respect to subjective and objective variables, either at short-term or at long-term follow-ups.
Psychological impact of thrombophilia testing in asymptomatic family members.

Psychological distress and worry are commonly described as potential consequences of genetic screening for various disorders. Thrombophilia testing may be offered to asymptomatic persons with a family history of venous thrombosis and thrombophilia. Our objectives were to measure the psychological impacts of thrombophilia testing in first degree relatives and to determine if our intervention, a more intensive care strategy to heighten awareness of both risk and symptoms of thrombosis, caused psychological distress.



First degree relatives of patients with a known thrombophilia and history of venous thrombosis were tested for thrombophilia. The Perceived Risk Questionnaire and validated psychological instruments (POMS-SF; SCL-90-R Somatization subscale) were administered before testing, one week after receiving results and a year later. Thrombophilia carriers were randomized in family clusters to receive Standard Care or the Intensive Care intervention.



There were 100 carriers who were randomized to Standard (n=48) or Intensive Care (n=52) and 103 non-carriers. One week after receiving results, we did not observe any difference in psychological distress between carriers and non-carriers, with low levels overall. At 1 year, psychological distress scores were similar between the Standard and Intensive Care arms and did not differ from baseline.



The results of this pilot study do not support the concern that thrombophilia screening in asymptomatic relatives triggers psychological distress and worry. Furthermore, our intensive educational approach did not appear to induce undue distress. While the positive benefits of thrombophilia screening remain unproven, clinicians should not be deterred from offering screening by the fear of causing psychological harm.