nils-herrmann/clean_scirepeval huggingface dataset:
Efficacy and safety of higher doses of botulinum toxin type A NT 201 free from complexing proteins in the upper and lower limb spasticity after stroke

Botulinum toxin type A (BTX-A) represents the gold standard therapy for focal spasticity after stroke, with low prevalence of complications, reversibility, and efficacy in reducing spastic hypertonia. Current guidelines suggest the employment of a dosage up to 600 units (U) of BTX-A to treat spasticity after stroke, to avoid important adverse effects and the development of antibodies against the neurotoxin. In recent years, NT 201, a new BTX-A free of complexing proteins, has been used for treating several movement disorders, showing safety and efficacy in upper limb spasticity. In a prospective, non-randomized, open-label study, we studied the efficacy and safety of higher doses of BTX-A NT 201 (up to 840 U) in 25 consecutive patients with upper and lower limb spasticity after stroke, evaluated at 30 and 90 days after injections. Before and after the treatment, the grade of spasticity, the disability, and spasticity-related pain were extensively measured. After 30 days of follow-up, a great reduction of spasticity and pain with improvement of disability was observed. The effects were still present at 90 days of follow-up. No major adverse events were observed. Higher doses of BTX-A NT 201 appeared to be safe and efficacious in patients with upper and lower limb spasticity after stroke. However, further investigations are needed to determine its reproducibility in larger case series or randomized clinical trials and to observe the absence of antibodies against the neurotoxin also after repeated injections.
A low-leakage dynamic multi-ported register file in 0.13mm CMOS

Increasing leakage currents combined with reduced noise margins are seriously degrading the robustness of dynamic circuits. This paper describes a dynamic implementation of a 256X32b 4-read/write-port Register-File for ~6GHz operation at 1.2V in a 0.13μm technology. The pre-charged local bit-lines utilize an efficient conditional keeper-technique, where a large fraction of the keeper is turned ON only if the dynamic output remains High in the evaluation phase. Using this technique, we are able to improve upon all-low-Vt performance by 4%, while maintaining Dual-Vt usage. Thus, the robustness is improved by 96% and the active leakage power is reduced by 5X.
Usefulness of ultrasonography is the evaluation of thyroid nodules.

To evaluate the diagnostic capacity of ultrasonography (US) for differentiating between malignant and benign thyroid nodules and its usefulness in obviating unnecessary invasive procedures.



From January 2012 through December 2014, a total of 321 fine-needle aspiration biopsy (FNAB) procedures were done in 302 patients selected according to the criteria recommended by the American Association of Clinical Endocrinology guidelines and the American Thyroid Association guidelines. We analyzed the following characteristics on US: location, size, morphology, contour, consistency, echostructure, echogenicity, calcifications, and vascularization. We used univariate and multivariate analyses to investigate the relationship between the US findings and thyroid cancer.



The prevalence of malignancy in our study population was 5.92%. The US findings that were significantly associated with a greater probability of malignancy were microcalcifications, central vascularization, and hypoechogenicity. The US findings that were associated with a lower risk of malignancy were areas of colloid degeneration and nodule heterogeneity.



Our results suggest that decisions about whether to perform FNAB should be based on the presence of suspicious US findings found with our statistic model rather than on the size of the nodule. Thus, unnecessary FNAB procedures on nodules without suspicious US characteristics can be avoided.
Biomarkers of body iron stores and risk of developing type 2 diabetes.

Iron may contribute to the pathogenesis of type 2 diabetes mellitus (DM) by inducing oxidative stress and interfering with insulin secretion. Elevated ferritin levels are associated with increased DM risk among healthy individuals. However, it is yet unknown if ferritin predicts DM incidence among high-risk individuals with impaired glucose tolerance (IGT). Furthermore, the association between soluble transferrin receptors (sTfR), a novel marker of iron status, and DM risk has not yet been prospectively investigated in these individuals. We conducted this study to evaluate the association between baseline levels of ferritin and sTfR and the risk of developing DM among overweight and obese individuals at high risk of DM.



This nested case-control study (280 cases and 280 matched controls) was conducted within the placebo arm of the Diabetes Prevention Program, is a clinical trial conducted among overweight/obese individuals with IGT. Ferritin and sTfR levels were measured by immunoturbidimetric assays. Incident DM was ascertained by annual 75-g oral glucose tolerance test and semi-annual fasting glucose.



Compared with controls, cases had higher sTfR levels (3.50 +/- 0.07 vs. 3.30 +/- 0.06 mg/l; p = 0.03), but ferritin levels were not statistically different. The multivariable odds ratios (OR) and 95% confidence intervals (95% CI) for DM incidence comparing highest with the lowest quartiles of sTfR was 2.26 (1.37-4.01) (p-trend: 0.008).



Modestly elevated sTfR levels are associated with increased DM risk among overweight and obese individuals with IGT. Future studies should evaluate factors determining sTfR levels and examine if interventions that lower body iron stores reduce DM incidence.
A method for registration of single photon emission computed tomography (SPECT) and computed tomography (CT) images for liver stereotactic radiotherapy (SRT).

To describe a simple method of coregistration of nonanatomic liver SPECT and CT images acquired in separate sessions for three-dimensional (3D)-CRT planning utilizing dual radiolabeled and radiopaque body surface markers, and evaluate the accuracy of the registration on the patient surface.



Ten patients treated for liver metastases or hepatocellular carcinoma with stereotactic body radiation therapy or 3D-CRT were selected for this study to evaluate the SPECT∕CT registration process. All patients were positioned in a custom-molded vacuum bag on the flat table top. Nine radiopaque markers were taped to the abdominal surface in three axial planes at the level of the liver. Following CT imaging, the nine radiopaque markers were then labeled with radioactive tags, each containing 10 μCi of (99m)Tc, and SPECT images were acquired. The metric used to evaluate the registration was the fiducial registration error (FRE), defined as the root mean square of the distance between pairs of homologous markers on the CT and SPECT images. The evaluation of the registration accuracy was performed in two steps: first the minimum number of markers necessary to obtain a robust registration was optimized; second the FRE was calculated on the remaining set of unused markers. Additionally, the deformation of the patient's abdominal surface between CT and SPECT acquisition sessions was evaluated using the distances between all possible unused marker pairs on the CT and SPECT images separately. The root mean square of the CT-to-SPECT difference between those distances was used to define the deformation index (DI). The registration method was evaluated on all ten patients in addition to an anthropomorphic phantom study.



The minimum number of markers above which the registration was not improved by more than 1 mm was 4. The FRE, calculated over the 5 remaining markers, was 6.1 mm for the patient population and 1.8 mm for the phantom study. The DI was 5.0 mm on average over all 10 patients and correlated well with the FRE. The DI was 1.6 mm for the phantom study, which represented the imaging systems' resolution and the ability to place the CT and SPECT markers at the exact same location.



It is feasible to use radiolabeled and radiopaque dual body surface markers for registration of SPECT and CT images acquired in separate sessions allowing conformal avoidance of SPECT-defined functional normal liver. Point-based rigid registration accuracy on the patient surface of 6.1 mm can be achieved using 4 dual body surface markers. The main contribution to the registration error is the deformation of the abdominal surface, arising from the inability to setup the patient in the exact same position at different times on two different imaging systems, and to properly account for breathing artifacts on the CT and SPECT images.
Carbamazepine and valproate monotherapy: feasibility, relative safety and efficacy, and therapeutic drug monitoring in manic disorder

Search for alternatives to lithium therapy for mood disorders commenced with anticonvulsants, carbamazepine (CBZ) and valproic acid (VPA), in the late 1970s. The comparative safety and efficacy data of CBZ and VPA monotherapy in patients with bipolar disorder remain to be established.  The main objectives of the study were to assess the relative anti-manic efficacy and safety of CBZ and VPA; to study the feasibility of using either, as a first line anti-manic agent; to investigate and generate clinically relevant parameters involving therapeutic drug monitoring of the two drugs.  After a 2-day screening period, suitable patients (n=30) were randomly assigned to treatment with CBZ or VPA. Both the drugs were started with an average dose of approximately 20 mg/kg body weight per day. Further increment in dose was carried out at weekly intervals, guided by clinical improvement, serum levels and treatment emergent adverse events. The primary efficacy measure in the protocol was defined as a change from baseline to endpoint in total score on the Young Mania Rating Scale. A favourable clinical response was defined a priori as a decrease of more than 50% from baseline in Young Mania Rating Scale total score.  Both CBZ and VPA were found to be efficacious as single first-line anti-manic agents, however VPA proved to be better. Using the intent-to-treat analysis, the VPA group showed a significant fall in YMRS total scores after week 1 while the CBZ group showed a significant fall after week 2. In the primary efficacy analysis, valproate group experienced significantly greater mean improvement in Young Mania Rating Scale total score than the CBZ group. Of the VPA treated patients, 73% showed a favourable clinical response while 53% of the patients on CBZ responded favourably. In the CBZ group, significantly more patients received rescue medication during the week 2 and the requirement was quantitatively more as compared to the VPA group. The steady state serum concentration (Css) of CBZ ranged from 3 to 9 µg/ml; however, it did not appear to correlate with the dose or clinical response. The Css of VPA ranged from 50 to 100 µg/ml; a linear correlation was found between the dose and serum levels of VPA as well as between weekly rise in serum levels and clinical response. Weekly dose escalations of VPA also correlated positively with corresponding rise in serum levels. Significantly more patients in the CBZ group reported adverse events, including nausea, vomiting and dizziness, than VPA.  The findings from this study suggest that both CBZ and VPA monotherapy is feasible for treatment of acute mania; however, VPA is more efficacious in terms of its early onset of action, lesser requirement for rescue medication and better tolerability. Further work needs to be undertaken to characterise the manic patients in terms of their differential psychopharmacologic response profile.
Eighth grade students become proficient at CPR and use of an AED following a condensed training programme.

To evaluate a new, 1-h, condensed training programme to teach continuous chest compression cardiopulmonary resuscitation (CCC-CPR) and automated external defibrillator (AED) skills to a cohort of eight grade public school students.



Thirty-three eligible subjects completed the programme; mean age 13.7 years; 48.5% female. Eight participants reported some prior training in CPR and AED use. Following initial training, 29/33 (87.8%) subjects demonstrated proficiency at CCC-CPR and AED application/operation in a mock adult cardiac arrest scenario. At four-weeks, 28/33 (84.8%) subjects demonstrated skill retention in similar scenario testing. Subjects also showed improvement in written knowledge regarding AED use as shown by scores on an AHA based written exam (60.9% versus 77.3%; p<0.001).



With our focused, condensed training program, eighth grade public school students became proficient in CCC-CPR and AED use. This is the first study to document the ability of middle school students to learn and retain CCC-CPR and AED skills for adult sudden cardiac arrest victims with such a curriculum.
Evaluation of Type Replacement Following HPV16/18 Vaccination: Pooled Analysis of Two Randomized Trials.

Current HPV vaccines do not protect against all oncogenic HPV types. Following vaccination, type replacement may occur, especially if different HPV types competitively interact during natural infection. Because of their common route of transmission, it is difficult to assess type interactions in observational studies. Our aim was to evaluate type replacement in the setting of HPV vaccine randomized controlled trials (RCTs).



Data were pooled from the Costa Rica Vaccine Trial (CVT; NCT00128661) and PATRICIA trial (NCT001226810)-two large-scale, double-blind RCTs of the HPV-16/18 AS04-adjuvanted vaccine-to compare cumulative incidence of nonprotected HPV infections across trial arms after four years. Negative rate difference estimates (rate in control minus vaccine arm) were interpreted as evidence of replacement if the associated 95% confidence interval excluded zero. All statistical tests were two-sided.



After applying relevant exclusion criteria, 21 596 women were included in our analysis (HPV arm = 10 750; control arm = 10 846). Incidence rates (per 1000 infection-years) were lower in the HPV arm than in the control arm for grouped nonprotected oncogenic types (rate difference = 1.6, 95% confidence interval [CI] = 0.9 to 2.3) and oncogenic/nononcogenic types (rate difference = 0.2, 95% CI = -0.3 to 0.7). Focusing on individual HPV types separately, no deleterious effect was observed. In contrast, a statistically significant protective effect (positive rate difference and 95% CI excluded zero) was observed against oncogenic HPV types 35, 52, 58, and 68/73, as well as nononcogenic types 6 and 70.



HPV type replacement does not occur among vaccinated individuals within four years and is unlikely to occur in vaccinated populations.
The Viborg vascular (VIVA) screening trial of 65-74 year old men in the central region of Denmark: study protocol

Screening for abdominal aortic aneurysm (AAA) of men aged 65-74 years reduces the AAA-related mortality and is generally considered cost effective. Despite of this only a few national health care services have implemented permanent programs. Around 10% of men in this group have peripheral arterial disease (PAD) defined by an ankle brachial systolic blood pressure index (ABI) below 0.9 resulting in an increased mortality-rate of 25-30%. In addition well-documented health benefits may be achieved through primary prophylaxis by initiating systematic cholesterol-lowering, smoking cessation, low-dose acetylsalicylic acid (aspirins), exercise, a healthy diet and blood-pressure control altogether reducing the increased risks for cardiovascular disease by at least 20-25%. The benefits of combining screening for AAA and PAD seem evident; yet they remain to be established. The objective of this study is to assess the efficacy and the cost-effectiveness of a combined screening program for AAA, PAD and hypertension.



The Viborg Vascular (VIVA) screening trial is a randomized, clinically controlled study designed to evaluate the benefits of vascular screening and modern vascular prophylaxis in a population of 50,000 men aged 65-74 years. Enrolment started October 2008 and is expected to stop in October 2010. The primary outcome is all-cause mortality. The secondary outcomes are cardiovascular mortality, AAA-related mortality, hospital services related to cardiovascular conditions, prevalence of AAA, PAD and potentially undiagnosed hypertension, health-related quality of life and cost effectiveness. Data analysis by intention to treat.



Major follow-up will be performed at 3, 5 and 10 years and final study result after 15 years.
Bolus injection of contrast agents with various iodine concentrations and delivery rates for intracranial three-dimensional CT angiography: evaluation of intracranial arteriovenous contrast using a multidetector-row CT scanner

We evaluated the difference in computed tomography (CT) attenuation values of the intracranial arterial and venous systems among the various contrast injection protocols (higher iodine delivery rate or higher concentration of the agent) on the source images of intracranial three-dimensional CT angiography (3D-CTA) using a multidetector-row CT (MDCT) scanner. We used 100 ml of iopamidol 300 at an injection rate of 3.0 ml/s, 100 ml of iopamidol 300 at an injection rate of 3.7 ml/s, and 80 ml of iopamidol 370 at an injection rate of 3.0 ml/s. There were 10 patients in each group. Attenuation values of the bilateral internal carotid arteries (ICAs), basilar artery trunk, bilateral cavernous sinuses (CSs), and Galenic vein were measured quantitatively on the axial CT angiographic source images obtained by four-channel MDCT. Injection of the high-concentration contrast with a higher iodine-delivery rate achieved good arteriovenous contrast at the cavernous portion. With the same rate of iodine delivery, injection of the intermediate concentrate agent increased the CT value of not only the ICAs but also the CSs. High-concentration contrast could increase ICA attenuation without intracavernous attenuation gain during the “first-pass” phase.
Acute hyperlipidemia but not hyperhomocysteinemia impairs reflex regulation of the cardiovascular system.

Elevated circulating lipids and homocysteine may affect autonomic cardiovascular function by decreasing baroreflex sensitivity (BRS) and cardiovagal outflow and by increasing sympathetic drive.



To test this hypothesis 25 clinically healthy men (mean age 24 ± 2 years) received 500 ml whipping cream (30% fat) and 0.1 g/kg l-methionine, respectively, at intervals of one week apart to induce hyperlipidemia and hyperhomocysteinemia, respectively. Cardiovascular parameters and endothelial function were assessed before and 2 h after the fat load and before and 4 h after the methionine load, respectively. Cardiovascular responses to sublingual application of a nitrovasodilator and a beta-agonist were also determined.



Hyperlipidemia elicited a significant decline in BRS and an increase in heart rate and sympathetic drive. Reductions in BRS were associated with changes in total cholesterol but not with triglycerides or endothelial function. Autonomic and hemodynamic variables remained unaltered during transient hyperhomocysteinemia although there was a trend to lower BRS. Autonomic and hemodynamic responses to pharmacological vasodilation and beta-adrenoceptor stimulation were preserved under both conditions.



These data provide experimental support for the concept that acute hyperlipidemia but not hyperhomocysteinemia impairs reflex regulation of the circulatory system.
[Effects of Mindfulness Meditation program on perceived stress, ways of coping, and stress response in breast cancer patients].

Purpose of this study was to examine the effects of the Mindfulness Meditation program on perceived stress, ways of coping, salivary cortisol level, and psychological stress response in patients with breast cancer.



This was a quasi-experimental study with a non-equivalent control group pre-post test design. Participants in this study were 50 patients who had completed breast cancer treatment (experimental group, 25, control group, 25). The experimental group received the Mindfulness Meditation program for 3 hours/session/ week for 8 weeks. Data were analyzed using χ²-test and t-test for subject homogeneity verification, and ANCOVA to examine the hypotheses.



The experimental group had significantly lower scores for perceived stress, emotional focused coping, salivary cortisol level, and psychological stress response compared to the control group. However, no significant differences were found between two groups for the scores on problem focused stress coping.



According to the results, the Mindfulness Meditation program was useful for decreasing perceived stress, emotional focused coping, salivary cortisol level, and psychological stress response. Therefore, this program is an effective nursing intervention to decrease stress in patients with breast cancer.
Revised GH and cortisol cut-points for the glucagon stimulation test in the evaluation of GH and hypothalamic–pituitary–adrenal axes in adults: results from a prospective randomized multicenter study

Recent studies suggest using lower GH cut-points for the glucagon stimulation test (GST) in diagnosing adult GH deficiency (GHD), especially in obese patients. There are limited data on evaluating GH and hypothalamic–pituitary–adrenal (HPA) axes using weight-based dosing for the GST. To define GH and cortisol cut-points to diagnose adult GHD and secondary adrenal insufficiency (SAI) using the GST, and to compare fixed-dose (FD: 1 or 1.5 mg in patients >90 kg) with weight-based dosing (WB: 0.03 mg/kg). Response to the insulin tolerance test (ITT) was considered the gold standard, using GH and cortisol cut-points of ≥3 ng/ml and ≥18 µg/dL, respectively. 28 Patients with hypothalamic-pituitary disease and 1–2 (n = 14) or ≥3 (n = 14) pituitary hormone deficiencies, and 14 control subjects matched for age, sex, estrogen status and body mass index (BMI) underwent the ITT, FD- and WB-GST in random order. Age, sex ratio and BMI were comparable between the three groups. The best GH cut-point for diagnosis of GHD was 1.0 (92 % sensitivity, 100 % specificity) and 2.0 ng/mL (96 % sensitivity and 100 % specificity) for FD- and WB-GST, respectively. Age negatively correlated with peak GH during FD-GST (r = −0.32, P = 0.04), but not WB-GST. The best cortisol cut-point for diagnosis of SAI was 8.8 µg/dL (92 % sensitivity, 100 % specificity) and 11.2 µg/dL (92 % sensitivity and 100 % specificity) for FD-GST and WB-GST, respectively. Nausea was the most common side effect, and one patient had a seizure during the FD-GST. The GST correctly classified GHD using GH cut-points of 1 ng/ml for FD-GST and 2 ng/ml for WB-GST, hence using 3 ng/ml as the GH cut-point will misclassify some GH-sufficient adults. The GST may also be an acceptable alternative to the ITT for evaluating the HPA axis utilizing cortisol cut-points of 9 µg/dL for FD-GST and 11 µg/dL for WB-GST.