nils-herrmann/clean_scirepeval huggingface dataset:
Changes of neural activity correlate with the severity of cortical ischemia in patients with unilateral major cerebral artery occlusion.

In major cerebral arterial steno-occlusive diseases, there can be remarkably decreased hemodynamic reserve without marked neurological impairments. In such settings, it is not known whether the neural activity is well maintained or disturbed according to the severity of cerebral ischemia. The present study was therefore undertaken to examine the neural activity under mild cerebral ischemia resulting from major cerebral arterial occlusion.



Seven patients with minor neurological impairment as well as either unilateral internal carotid artery or middle cerebral artery occlusion were studied. The severity of the cortical ischemia was assessed by measuring regional cerebral blood flow (rCBF) with positron emission tomography. The change in neural activity in the ischemic brain was then evaluated by means of somatosensory evoked magnetic field with magnetoencephalography.



The rCBF in the primary sensory area and the strength of the initial component of somatosensory evoked magnetic field (N20 m) were significantly reduced (P<0.01) and the second component (P30 m) was significantly augmented (P<0.05) in the lesioned cerebral hemisphere as compared with the nonlesioned hemisphere. The asymmetry indexes for N20 m were positively correlated (r=0.78) and those for P30 m were inversely correlated (r=-0.92) with asymmetry indexes for rCBF.



In patients with either unilateral internal carotid artery or middle cerebral artery occlusion and minor neural impairments, there was a reduction of afferent signal and an augmentation of the secondary response of the neurons in the primary sensory area. This showed correlation with the severity of cortical ischemia.
Factors affecting accessibility and acceptability of voluntary counselling and testing among high risk group (HRG) for human immunodeficiency virus (HIV) in NWFP Pakistan.

To identify the factors that affect the accessibility and acceptability of Voluntary Counselling and Testing (VCT) services among High Risk Groups for HIV in NWFP.



A cross sectional study was conducted in two districts of N.W.F.P. namely Peshawar and Abbotabad from August 2007 up till January 2008. A total of 153 participants were interviewed from high risk group by convenient sampling. The high risk group included commercial sex workers and injection drug users. Information was also gathered from in-charges of VCT centers. The data were collected in two phases, in the first phase data were collected in Peshawar while in the second phase data were collected in Abbotabad. Out of 153 respondents 102 (67%) were interviewed in Peshawar while 51 (33%) respondents were interviewed in Abbotabad.



A total of 153 respondents were interviewed, that included commercial sex workers (123) and injection drug users (30). Mostly the participants were young with a mean age of 24 +/- 8.8 years. As far as transmission of HIV was concerned 57% reported that HIV was transmitted through sexual contact, 09% said it was transmitted by contaminated instruments and syringes and around 11% reported its transmission by eating with persons having HIV/AIDS while 04% said it was transmitted by hugging/kissing. The level of knowledge about VCT was very low and about 27% of the participants had heard about VCT center. Only a small number i.e., 16 out of 153 partipants visited VCT centres.



The study concluded that there is lackof awareness among high risk group regarding VCT and those who have heard about VCT (27%) only a few had visited the VCT center. The awareness campaign about VCT should target communities in general and high risk group in particular.
Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension.

Patients with essential hypertension have disturbed autonomic cardiovascular regulation and circadian pacemaker function. Recently, the biological clock was shown to be involved in autonomic cardiovascular regulation. Our objective was to determine whether enhancement of the functioning of the biological clock by repeated nighttime melatonin intake might reduce ambulatory blood pressure in patients with essential hypertension. We conducted a randomized, double-blind, placebo-controlled, crossover trial in 16 men with untreated essential hypertension to investigate the influence of acute (single) and repeated (daily for 3 weeks) oral melatonin (2.5 mg) intake 1 hour before sleep on 24-hour ambulatory blood pressure and actigraphic estimates of sleep quality. Repeated melatonin intake reduced systolic and diastolic blood pressure during sleep by 6 and 4 mm Hg, respectively. The treatment did not affect heart rate. The day-night amplitudes of the rhythms in systolic and diastolic blood pressures were increased by 15% and 25%, respectively. A single dose of melatonin had no effect on blood pressure. Repeated (but not acute) melatonin also improved sleep. Improvements in blood pressure and sleep were statistically unrelated. In patients with essential hypertension, repeated bedtime melatonin intake significantly reduced nocturnal blood pressure. Future studies in larger patient group should be performed to define the characteristics of the patients who would benefit most from melatonin intake. The present study suggests that support of circadian pacemaker function may provide a new strategy in the treatment of essential hypertension.
Summation in finite terms using sage

The summation analogue of the Risch integration algorithm developed by Karr [4, 5] uses towers of difference fields to model nested indefinite sums and products, as the Risch algorithm uses towers of differential fields to model the so called elementary functions . The algorithmic machinery developed by Karr, and later generalized and extended in [1, 13, 7, 6], allows one to find solutions of first order difference equations over such towers of difference fields, in turn simplifying expressions involving sums and products. We present an implementation of this machinery in the open source computer algebra system Sage . Due to the nature of open source software, this allows direct experimentation with the algorithms and structures involved while taking advantage of the state of the art primitives provided by Sage. Even though these methods are used behind the scenes in the summation package Sigma  and they were previously implemented in , this is the first open source implementation.
A pre-visit tailored website enhances counselees’ realistic expectations and knowledge and fulfils information needs for breast cancer genetic counselling

Counselees who are the first in their family to request breast cancer genetic counselling often don’t know what to expect or have unrealistic expectations of genetic counselling. Receiving tailored information might help them to prepare for their first visit. We conducted a study of the effects of a pre-visit website providing computer-tailored information (E-info geneca), on counselees’ expectations, knowledge about breast cancer and heredity and information needs. Counselees were randomized to receive usual care (UC) or UC plus website. All counselees completed a baseline questionnaire and those randomized to the intervention group also completed a questionnaire after having viewed the website. After having accessed E-info geneca counselees (n = 101) better knew what to expect of their first visit (χ2 = 4.43; P = .04) and less often showed unrealistic expectations about possibilities for DNA-testing (χ2 = 4.84; P = .03) than counselees in the UC group (n = 89). In addition, the website increased counselees’ knowledge of breast cancer and heredity (B = .23; P = .003) and lowered their information needs (B = −.16; P = .000) compared to the UC group. Especially, information concerning procedural aspects and emotional consequences of genetic counselling was considered less important. This study showed that counselees know more and need less when they are provided with extended pre-visit information through a tailored website and counselees enter the visit with more realistic expectations of genetic counselling. This might facilitate and focus communication within the subsequent consultation.
Physiologic response to changing positive end-expiratory pressure during neurally adjusted ventilatory assist in sedated, critically ill adults.

Neurally adjusted ventilatory assist (NAVA) delivers airway pressure (Paw) in proportion to neural inspiratory drive as reflected by electrical activity of the diaphragm (EAdi). Changing positive end-expiratory pressure (PEEP) impacts respiratory muscle load and function and, hence, EAdi. We aimed to evaluate how PEEP affects the breathing pattern and neuroventilatory efficiency during NAVA.



In 20 adult patients, adequate assist (NAVAal) was first identified based on Paw and tidal volume (Vt) responses to systematic increases in NAVA level while using preset PEEP (PEEPbl). Thereafter, using NAVAal, PEEP was increased to 20 cm water (H(2)O) (PEEPhigh) and then lowered stepwise to 1 cm H(2)O (PEEP1). EAdi, Paw, and Vt were recorded.



Median NAVAal was 2.7 (interquartile range, 2.3-3.5) cm H(2)O/muV and was similar to NAVAal identified post hoc by 17 independent physicians (2.5 [2.0-3.4] cm H(2)O/muV; P = NS). Reducing PEEPhigh to PEEP1 increased inspiratory EAdi by 34% (2-67; P = .046) and was associated with an increase in mean Paw above PEEP from 8.5 (6.7-11.4) cm H(2)O to 12.2 (8.8-16.7) cm H(2)O (P = .008), whereas Vt and respiratory rate remained unchanged. The response pattern in Vt/EAdi, indicating changes in neuroventilatory efficiency, differed among patients. Tidal breathing occurred at the lowest EAdi cost in seven patients with PEEP1 or half PEEPbl, in six patients with PEEPbl, and in seven patients with PEEPhigh.



During NAVAal, increasing PEEP reduces respiratory drive. Patients adapt their neuroventilatory efficiency such that the individual ventilatory pattern is preserved over a wide range of PEEP levels. Monitoring Vt/EAdi during PEEP changes allows identification of a PEEP level at which tidal breathing occurs at minimal EAdi cost.
Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): a randomised, open-label study

Glucagon-like peptide-1 receptor agonists exenatide and liraglutide have been shown to improve glycaemic control and reduce bodyweight in patients with type 2 diabetes. We compared the efficacy and safety of exenatide once weekly with liraglutide once daily in patients with type 2 diabetes.



We did a 26 week, open-label, randomised, parallel-group study at 105 sites in 19 countries between Jan 11, 2010, and Jan 17, 2011. Patients aged 18 years or older with type 2 diabetes treated with lifestyle modification and oral antihyperglycaemic drugs were randomly assigned (1:1), via a computer-generated randomisation sequence with a voice response system, to receive injections of once-daily liraglutide (1·8 mg) or once-weekly exenatide (2 mg). Participants and investigators were not masked to treatment assignment. The primary endpoint was change in glycated haemoglobin (HbA(1c)) from baseline to week 26. Analysis was by intention to treat. 
Of 912 randomised patients, 911 were included in the intention-to-treat analysis (450 liraglutide, 461 exenatide). The least-squares mean change in HbA(1c) was greater in patients in the liraglutide group (-1·48%, SE 0·05; n=386) than in those in the exenatide group (-1·28%, 0·05; 390) with the treatment difference (0·21%, 95% CI 0·08-0·33) not meeting predefined non-inferiority criteria (upper limit of CI <0·25%). The most common adverse events were nausea (93 [21%] in the liraglutide group vs 43 [9%] in the exenatide group), diarrhoea (59 [13%] vs 28 [6%]), and vomiting 48 [11%] vs 17 [4%]), which occurred less frequently in the exenatide group and with decreasing incidence over time in both groups. 24 (5%) patients allocated to liraglutide and 12 (3%) allocated to exenatide discontinued participation because of adverse events.



Both once daily liraglutide and once weekly exenatide led to improvements in glycaemic control, with greater reductions noted with liraglutide. These findings, plus differences in injection frequency and tolerability, could inform therapeutic decisions for treatment of patients with type 2 diabetes.



Eli Lilly and Company and Amylin Pharmaceuticals LLC.
Dose-Response Effects of Insulin Glargine in Type 2 Diabetes

To determine the pharmacokinetic and pharmacodynamic dose-response effects of insulin glargine administered subcutaneously in individuals with type 2 diabetes.



Twenty obese type 2 diabetic individuals (10 male and 10 female, aged 50 +/- 3 years, with BMI 36 +/- 2 kg/m(2) and A1C 8.3 +/- 0.6%) were studied in this single-center, placebo-controlled, randomized, double-blind study. Five subcutaneous doses of insulin glargine (0, 0.5, 1.0, 1.5, and 2.0 units/kg) were investigated on separate occasions using the 24-h euglycemic clamp technique.  Glargine duration of action to reduce glucose, nonessential fatty acid (NEFA), and beta-hydroxybutyrate levels was close to or >24 h for all four doses. Increases in glucose flux revealed no discernible peak and were modest with maximal glucose infusion rates of 9.4, 6.6, 5.5, and 2.8 mumol/kg/min for the 2.0, 1.5, 1.0, and 0.5 units/kg doses, respectively. Glargine exhibited a relatively hepatospecific action with greater suppression (P < 0.05) of endogenous glucose production (EGP) compared with little or no increases in glucose disposal.



A single subcutaneous injection of glargine at a dose of >or=0.5 units/kg can acutely reduce glucose, NEFA, and ketone body levels for 24 h in obese insulin-resistant type 2 diabetic individuals. Glargine lowers blood glucose by mainly inhibiting EGP with limited effects on stimulating glucose disposal. Large doses of glargine have minimal effects on glucose flux and retain a relatively hepatospecific action in type 2 diabetes.
An integrated multi-study analysis of intra-subject variability in cerebrospinal fluid amyloid-β concentrations collected by lumbar puncture and indwelling lumbar catheter

Amyloid-β (Aβ) has been investigated as a diagnostic biomarker and therapeutic drug target. Recent studies found that cerebrospinal fluid (CSF) Aβ fluctuates over time, including as a diurnal pattern, and increases in absolute concentration with serial collection. It is currently unknown what effect differences in CSF collection methodology have on Aβ variability. In this study, we sought to determine the effect of different collection methodologies on the stability of CSF Aβ concentrations over time. Grouped analysis of CSF Aβ levels from multiple industry and academic groups collected by either lumbar puncture (n=83) or indwelling lumbar catheter (n=178). Participants were either placebo or untreated subjects from clinical drug trials or observational studies. Participants had CSF collected by lumbar puncture or lumbar catheter for quantitation of Aβ concentration by enzyme linked immunosorbent assay. Data from all sponsors was converted to percent of the mean for Aβ40 and Aβ42 for comparison. Repeated measures analysis of variance was performed to assess for factors affecting the linear rise of Aβ concentrations over time. Analysis of studies collecting CSF via lumbar catheter revealed tremendous inter-subject variability of Aβ40 and Aβ42 as well as an Aβ diurnal pattern in all of the sponsors’ studies. In contrast, Aβ concentrations from CSF samples collected at two time points by lumbar puncture showed no significant differences. Repeated measures analysis of variance found that only time and draw frequency were significantly associated with the slope of linear rise in Aβ40 and Aβ42 concentrations during the first 6 hours of collection. Based on our findings, we recommend minimizing the frequency of CSF draws in studies measuring Aβ levels and keeping the frequency standardized between experimental groups. The Aβ diurnal pattern was noted in all sponsors’ studies and was not an artifact of study design. Averaging Aβ concentrations at each time point is recommended to minimize the effect of individual variability. Indwelling lumbar catheters are an invaluable research tool for following changes in CSF Aβ over 24-48 hours, but factors affecting Aβ concentration such as linear rise and diurnal variation need to be accounted for in planning study designs.
Cost Effectiveness of Budesonide/Formoterol for Maintenance and Reliever Therapy versus Salmeterol/ Fluticasone plus Salbutamol in the Treatment of Asthma

Budesonide/formoterol (Symbicort®) Maintenance And Reliever Therapy (SMART) is an effective and well tolerated treatment option for patients with asthma. We compared the cost effectiveness from a societal perspective of this one-inhaler regimen with that of maintenance salmeterol/fluticasone propionate (Seretide®) plus salbutamol (albuterol) as needed (Seretide® Fixed Combination [SFC]).  A cost-effectiveness analysis was performed based on effectiveness and resource-utilisation data collected prospectively in a randomised, 12-month study performed in 2143 patients in 16 countries. Resource utilisation data were pooled and unit costs (€, year 2003 values) from Italy, France, the UK and Germany were used to generate estimates of direct and total costs per patient per year and cost per severe exacerbation avoided.  Adolescents and adults with asthma (n = 2143; mean forced expiratory volume in 1 second [FEV1] 73% predicted; mean inhaled corticosteroid [ICS] dose 884 µg/day) were randomised to SMART or SFC. The effectiveness measure used was the number of severe exacerbations per patient per year. Direct costs included medication use (budesonide/formoterol 160µg/4.5µg or salmeterol/fluticasone 50µg/100µg, 50µg/250µg or 50µg/500µg plus salbutamol) and nonmedication-related resource use, including days in hospital, emergency room visits, specialist or primary care physician visits and other healthcare provider contacts. Indirect costs, including the number of days when the patient or their carer was unable to attend to their normal daily activities, were also assessed. The study assumed a European societal perspective (i.e. including direct and indirect costs).  Treatment with SMART resulted in significantly fewer severe exacerbations per patient per year compared with SFC (0.24 vs 0.31 events per patient per year; p = 0.0025). Resource use was low in both groups. Medication costs accounted for the majority of the total costs. The increased effectiveness of SMART was achieved at a reduced or similar cost compared with SFC. SMART dominated when German unit costs were applied (i.e. there was a statistically significant reduction in both costs and number of exacerbations). In all other countries, the incremental cost-effectiveness ratios showed that there was a reduction in mean total cost per exacerbation avoided; however, this difference was not statistically significant.  This analysis demonstrates that, compared with SFC, SMART may be cost effective from a societal perspective for the treatment of patients with asthma in Italy, Germany, France and the UK. SMART provided a reduction in the number of severe exacerbations per patient per year, at no statistically significant increase in cost — or even at a lower cost — compared with SFC plus as-needed reliever salbutamol.
Sodium pentosan polysulfate resulted in cartilage improvement in knee osteoarthritis - An open clinical trial-

Pentosan polysulfate sodium (pentosan) is a semi-synthetic drug manufactured from beech-wood hemicellulose by sulfate esterification of the xylopyranose hydroxyl groups. From in vitro and animal model studies, pentosan has been proposed as a disease modifying osteoarthritis drug (DMOAD). The objective of this study was to assess the efficacy, safety, and patient satisfaction in patients with mild radiographic knee osteoarthritis (OA) findings and OA-associated symptoms and signs.



Twenty patients were assessed clinically at Nagasaki University Hospital. The radiographic indications of OA were grade 1 to 3 using the Kellgren-Lawrence Grading System (K/L grade). Pentosan used in this study was manufactured and supplied in sterile injectable vials (100 mg/ml) by bene GmbH, Munich, Germany. The study was a single-center, open-label trial. Treatment consisted of 6 weekly subcutaneous injections (sc) of pentosan (2 mg/kg). Patients were clinically assessed at entry and 1 to 8, 11, 15, 24 & 52 weeks post treatment. The results were analyzed using one way ANOVA and Dunnett's method.



Hydrarthroses were reduced quickly in all cases. The clinical assessments, i.e., knee flexion, pain while walking, pain after climbing up and down stairs, etc, were improved significantly and these clinical improvements continued for almost one year. The dose used in this study affected the blood coagulation test, but was within safe levels. Slightly abnormal findings were noted in serum triglycerides.



Pentosan treatment in twenty patients with mild knee OA seemed to provide improvements in clinical assessments and C2C level of cartilage metabolism.
A human epidermal growth factor receptor 2 expression-based approach to neoadjuvant chemotherapy for operable breast cancer.

We investigated the pathological effects of neoadjuvant chemotherapy based on the human epidermal growth factor receptor 2 in operable breast cancer.



This prospective clinical study was a pilot involving 63 female patients. Before surgery, patients with tumors overexpressing human epidermal growth factor receptor 2 received four cycles of 60 mg/m(2) anthracycline and 600 mg/m(2) cyclophosphamide every 3 weeks, whereas those whose tumors did not overexpress human epidermal growth factor receptor 2 received four cycles of 75 mg/m(2) docetaxel and 600 mg/m(2) cyclophosphamide every 3 weeks. A quasi-pathological complete response (i.e. absence of invasive tumor or only focal residual tumor cells) was the primary endpoint, with compliance and predictors for each regimen as secondary endpoints. If a quasi-pathological complete response was not achieved, then crossover to the alternative treatment was recommended.



The quasi-pathological complete response rate was 36.5% (23 of 63) overall, 27.8% (5 of 18) for the anthracycline and cyclophosphamide regimen and 40.0% (18 of 45) for the docetaxel and cyclophosphamide regimen. Docetaxel and cyclophosphamide treatment induced a quasi-pathological complete response in most patients with triple-negative tumors (15 of 19). The relative dose intensity was 97.3% for the anthracycline and cyclophosphamide regimen and 96.6% for the docetaxel and cyclophosphamide regimen. Quasi-pathological complete response to the docetaxel and cyclophosphamide regimen was associated with low estrogen receptor and progesterone receptor expression and high MIB-1 and topoisomerase IIalpha expression, in univariate analyses, but only with low estrogen receptor expression in multivariate analysis.



Selecting neoadjuvant chemotherapy regimens on the basis of individual human epidermal growth factor receptor 2 status improved efficacy, with docetaxel and cyclophosphamide treatment showing particular promise in tumors with the potential to be highly malignant.