nils-herrmann/clean_scirepeval huggingface dataset:
Impact of Cerebrospinal Fluid Shunting for Idiopathic Normal Pressure Hydrocephalus on the Amyloid Cascade

The aim of this study was to determine whether the improvement of cerebrospinal fluid (CSF) flow dynamics by CSF shunting, can suppress the oligomerization of amyloid β-peptide (Aβ), by measuring the levels of Alzheimer's disease (AD)-related proteins in the CSF before and after lumboperitoneal shunting. Lumbar CSF from 32 patients with idiopathic normal pressure hydrocephalus (iNPH) (samples were obtained before and 1 year after shunting), 15 patients with AD, and 12 normal controls was analyzed for AD-related proteins and APLP1-derived Aβ-like peptides (APL1β) (a surrogate marker for Aβ). We found that before shunting, individuals with iNPH had significantly lower levels of soluble amyloid precursor proteins (sAPP) and Aβ38 compared to patients with AD and normal controls. We divided the patients with iNPH into patients with favorable (improvement ≥ 1 on the modified Rankin Scale) and unfavorable (no improvement on the modified Rankin Scale) outcomes. Compared to the unfavorable outcome group, the favorable outcome group showed significant increases in Aβ38, 40, 42, and phosphorylated-tau levels after shunting. In contrast, there were no significant changes in the levels of APL1β25, 27, and 28 after shunting. After shunting, we observed positive correlations between sAPPα and sAPPβ, Aβ38 and 42, and APL1β25 and 28, with shifts from sAPPβ to sAPPα, from APL1β28 to 25, and from Aβ42 to 38 in all patients with iNPH. Our results suggest that Aβ production remained unchanged by the shunt procedure because the levels of sAPP and APL1β were unchanged. Moreover, the shift of Aβ from oligomer to monomer due to the shift of Aβ42 (easy to aggregate) to Aβ38 (difficult to aggregate), and the improvement of interstitial-fluid flow, could lead to increased Aβ levels in the CSF. Our findings suggest that the shunting procedure can delay intracerebral deposition of Aβ in patients with iNPH.
Analytical performance and diagnostic accuracy of immunometric assays for the measurement of circulating oxidized LDL.

Oxidized LDL (ox-LDL) plays an important role in the pathogenesis of coronary heart disease (CHD). Several tests for circulating ox-LDL have been published. We believe it is critical to carefully evaluate these assays because small differences in performance may have profound effects when results are compared; we therefore compared the analytical and clinical performances of 2 assays: one developed in our laboratory and a commercial assay (Mercodia) that uses the same monoclonal antibody (4E6).



We determined the variance of ox-LDL in both tests, including its longitudinal stability (n = 225; 3 time points per person) and its diagnostic accuracy, by ROC analysis of 95 consecutive CHD patients and 20 controls.



The between-person variability was 77% for the in-house assay (with the remaining 23% being within-person and analytical variance) and 74% for the commercial assay. For comparison, previously reported values were 66% for high-sensitivity C-reactive protein and 82% for total cholesterol. The areas under the curves for CHD in the 2 assays were identical (0.85). The odds ratios (logistic regression) for CHD among persons with high ox-LDL (>or=15 mg/L) compared with persons with low ox-LDL were not different: 4.3 (95% confidence interval, 1.4-12) for the in-house assay and 3.3 (1.1-10) for the commercial assay.



The longitudinal stability of ox-LDL, as assessed by multiple measures in people over time, is similar to that of total cholesterol and high-sensitivity C-reactive protein. Both assays tested similarly distinguish between healthy controls and CHD patients.
Training Endogenous Task Shifting Using Music Therapy: A Feasibility Study.

People with acquired brain injury (ABI) are highly susceptible to disturbances in executive functioning (EF), and these effects are pervasive. Research studies using music therapy for cognitive improvement in this population are limited.



The purpose of this study was to determine the feasibility of a Musical Executive Function Training (MEFT) intervention to address task-shifting skills in adults with ABI and to obtain preliminary evidence of intervention effect on task shifting.



Fourteen participants were randomly assigned to one of three groups: a music therapy intervention group (MTG), a singing group (SG), or the no-intervention control group (CG). The SG and MTG met for one hour a day for five days. Feasibility measures included participant completion rates and intervention fidelity. Potential benefits were measured using the Trail Making Test and the Paced Auditory Serial Addition Task as a pre- and posttest measure.



Participant completion rates and interventionist fidelity to the protocol supported feasibility. One-way ANOVA of the pre- and posttest group differences revealed a trend toward improvement in the MTG over the SG.



Feasibility and effect size data support a larger trial of the MEFT protocol.
Metabolic parameters in the short- and long-term treatment of schizophrenia with sertindole or risperidone

The presence of the metabolic syndrome is an important risk factor for cardiovascular disease and diabetes. The short- and long-term metabolic safety of sertindole was compared to that of risperidone in a subset of patients enrolled in the sertindole cohort prospective (SCoP) study, an open randomized study. In 261 randomized patients, there were moderate increases in mean weight, BMI, and waist circumference during treatment with either sertindole or risperidone; after 12 weeks, the increase in weight was 1.3 and 1.1 kg, respectively, and after 36 weeks, it was 2.2 and 2.0 kg, respectively. From baseline to last assessment (up to 60 weeks), weight gains of 1.8 and 1.7 kg for sertindole and risperidone, respectively, were observed. Similar proportions of patients (sertindole: 17% versus risperidone: 16%) had weight increases ≥7% from baseline to last assessment. The mean changes from baseline in triglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol, plasma glucose and blood pressure were small and not clinically relevant in both treatment groups. No patient in either of the groups developed type 2 diabetes during the study. At last assessment, the prevalence of metabolic syndrome (International Diabetes Federation) was 17% in the sertindole group and 26% in the risperidone group and the incidence of metabolic syndrome was 7% in the sertindole group and 10% in the risperidone group. Treatment with either sertindole or risperidone did not appear to be associated with an increased comparative risk of developing metabolic syndrome. In general, the metabolic effects of sertindole and risperidone were similar.
Proliferation, steroid receptors and clinical/pathological response in breast cancer treated with letrozole

Sixty-three postmenopausal women with large primary breast cancers were treated with neoadjuvant letrozole (2.5 mg daily) for 3 months. Tumour samples were taken at diagnosis and after 10–14 days and 3 months treatment. Immunohistochemical staining for Ki67, oestrogen receptor (ER) and progesterone receptor (PgR) was performed and related to clinical (ClinR) and pathological responses (PathR) after 3 months treatment. ClinR was observed in 48 of 63 cases (76.2%) and PathR in 47 of 62 (75.8%). Pretreatment Ki67 scores were similar in responders (R) and non-responders (NR). Highly significant Ki67 decreases occurred in all tumour subgroups at 10–14 days (P<0.005). A significant difference in Ki67 scores at 10–14 days (P<0.007) was found between PathR and PathNR but not between ClinR and ClinNR. At 3 months, decreases from pretreatment Ki67 scores were highly significant in all tumour subgroups irrespective of response status. However, whereas Ki67 scores were significantly different between pathological R and NR (P=0.009), the corresponding comparison of ClinR status was not. Significant decreases between 10–14 days and 3 months were found only in ClinR and PathR (P=0.02 and 0.045, respectively). Treatment significantly reduced PgR expression at 14 days and 3 months (both P<0.0001), but the level of changes was not different between response status groups. In summary, letrozole produces rapid and profound decreases in expression of Ki67 and PgR but changes do not always correlate with clinical and pathological responses.
Roles of nitric oxide and prostaglandins in the hyperemic response to a maximal metabolic stimulus: redundancy prevails

Vasodilatory mechanisms controlling post-exercise or post-ischemic hyperemia are thought to be under redundant control and remain incompletely understood. A maximal metabolic stimulus evoked by ischemic exercise (IE) might limit redundancy by full activation of multiple pathways. We tested whether nitric oxide (NO) and/or prostaglandins contribute to the hyperemic response to IE. 17 subjects were randomized into two groups and performed three trials of IE during control (saline), N G-monomethyl-l-arginine (l-NMMA; NOS inhibition) (protocol 1) or ketorolac (cyclooxygenase inhibition) infusion (protocol 2), and combined l-NMMA/ketorolac infusion via a brachial arterial catheter. Forearm blood flow (FBF) was measured with venous occlusion plethysmography following IE trials consisting of 5 min of ischemia and simultaneous rhythmic handgrip exercise (final 2 min). Peak and total (area under the curve) FBF and blood pressure (MAP) were measured for 3 min after each trial. Forearm vascular conductance (FVC) was calculated as FBF/MAP. Change (Δ) in peak FBF and FVC from baseline differed only between peak FBF for the saline and l-NMMA + ketorolac trials in protocol 1. Peak ΔFBF was 26.8 ± 2.5, 30.0 ± 2.8, and 33.9 ± 3.6 ml 100 ml−1 min−1 for saline, l-NMMA, and l-NMMA + ketorolac trials (P = 0.04). For protocol 1 (n = 8), total ΔFVC was 59.6 ± 4.3, 57.8 ± 6.0, and 59.9 ± 5.6 ml 100 ml−1 100 mmHg−1 for saline, l-NMMA, and l-NMMA + ketorolac trials, (P = 0.82). For protocol 2 (n = 9), total ΔFVC was 54.2 ± 5.0, 56.9 ± 4.5, and 56.5 ± 5.3 ml 100 ml−1 100 mmHg−1 for saline, ketorolac, and ketorolac + l-NMMA trials, (P = 0.69). These results suggest that NO and PGs are not obligatory for the hyperemic response to IE, and other vasodilator mechanisms predominate.
Review of Modelling Techniques for In Vivo Muscle Force Estimation in the Lower Extremities during Strength Training

Knowledge of the musculoskeletal loading conditions during strength training is essential for performance monitoring, injury prevention, rehabilitation, and training design. However, measuring muscle forces during exercise performance as a primary determinant of training efficacy and safety has remained challenging.



In this paper we review existing computational techniques to determine muscle forces in the lower limbs during strength exercises in vivo and discuss their potential for uptake into sports training and rehabilitation.



Muscle forces during exercise performance have almost exclusively been analysed using so-called forward dynamics simulations, inverse dynamics techniques, or alternative methods. Musculoskeletal models based on forward dynamics analyses have led to considerable new insights into muscular coordination, strength, and power during dynamic ballistic movement activities, resulting in, for example, improved techniques for optimal performance of the squat jump, while quasi-static inverse dynamics optimisation and EMG-driven modelling have helped to provide an understanding of low-speed exercises.



The present review introduces the different computational techniques and outlines their advantages and disadvantages for the informed usage by nonexperts. With sufficient validation and widespread application, muscle force calculations during strength exercises in vivo are expected to provide biomechanically based evidence for clinicians and therapists to evaluate and improve training guidelines.
White matter lesions as a feature of cognitive impairment, low vitality and other symptoms of geriatric syndrome in the elderly.

White matter lesions (WML) are common findings on magnetic resonance imaging (MRI) in elderly persons. In this study, we analyzed the relation of WML with global cognitive function, depression, vitality/volition, and 19 symptoms of geriatric syndrome in Japanese elderly patients who attended three university geriatric outpatient clinics.



Two hundred and eighty-six subjects (103 men and 183 women; mean +/- standard deviation age, 74.5 +/- 7.8 years) were included in this study. MRI scans were performed for the diagnosis of WML, and the severity of periventricular and deep white matter hyperintensities (PVH and DWMH) was rated semiquantitatively. Concurrently, all subjects underwent tests of cognitive function, depressive state and vitality, and were examined for 19 symptoms of geriatric syndrome.



The study subjects showed cognitive decline, depression and low vitality, all to a mild extent. Univariate linear regression analysis showed a negative correlation between the severity of WML and cognitive function or vitality. Multiple logistic analysis revealed that the severity of WML was a significant determinant of cognitive impairment and low vitality, after adjustment for confounding factors such as age, sex and concomitant diseases. PVH and/or DWMH score was significantly greater in subjects who exhibited 13 out of 19 symptoms of geriatric syndrome. Logistic regression analysis indicated that WML were associated with psychological disorders, gait disturbance, urinary problems and parkinsonism.



WML were associated with various symptoms of functional decline in older persons. Evaluating WML in relation to functional decline would be important for preventing disability in elderly people.
Radiological versus surgical implantation of first catheter for peritoneal dialysis: a randomized non-inferiority trial.

The success of peritoneal dialysis (PD) is dependent on timely and adequate PD catheter access. In many centres, including our own, PD catheter insertion technique has evolved by laparoscopic surgery. An alternative method of catheter insertion is performed by radiologists using a percutaneous modified Seldinger technique under fluoroscopic guidance. However, there are no clinical trials comparing these two methods of catheter insertion.



From 1 April 1999 to 30 August 2004, we randomly assigned 113 pre-dialysis patients to receive PD catheter insertion using fluoroscopic guidance under local anaesthesia by radiologists or insertion using laparoscopy under general anaesthesia by a surgeon. The primary endpoint was the occurrence of dialysis catheter complications (complication-free catheter survival) by Day 365, a composite endpoint that included complications secondary to mechanical and infectious causes. Secondary endpoints were the occurrence of catheter removal (overall catheter survival) and death from any cause (patient survival) by Day 365, procedure pain, procedure time, procedure room utilization time, length of inpatient admission and direct hospital costs. Results were analysed by univariate and multivariate methods and by Kaplan-Meier survival curves.



Complication-free catheter survival was significantly higher at 42.5% [95% confidence interval (CI) 29.3-55] in the radiological group compared with 18.1% (95% CI 8.9-29.8) in the laparoscopic group (P-value = 0.03). Excess complications in the laparoscopic group included peritonitis, peritoneal dialysate leaks and umbilical herniae. One-year overall catheter survival and 1-year subject survival were not different between the groups. Hospital costs were significantly higher in the laparoscopic group by almost a factor of two.



Radiological insertion of first PD catheters using fluoroscopy is a clinically non-inferior and cost-effective alternative to surgical laparoscopic insertion.
Case-control study of oral contraceptive use and risk of breast cancer.

The relation of oral contraceptive use to the risk of breast cancer in white women aged 25-59 years was assessed with data collected during 1977-1992 in a case-control surveillance system in hospitals in Boston, New York, and Philadelphia. A total of 3,540 cases with breast cancer were compared with 4,488 controls with nonmalignant nongynecologic conditions unrelated to oral contraceptive use. Relative risk estimates were obtained by unconditional logistic regression with control for major risk factors. For at least 1 year of use relative to less than 1 year, the multivariate relative risk estimate was 1.7 (95% confidence interval (CI) 1.3-2.3) in women aged 25-34 years, 0.9 (95% CI 0.7-1.0) in women aged 35-44 years, and 1.2 (95% CI 1.0-1.4) in women aged 45-59 years (p < 0.01 for the difference across age). Among women aged 25-34 years, the relative risk estimates were greatest for use of long duration, but the trend was not statistically significant (p = 0.17); in addition, the duration of use was correlated with the recency of use, and it was not possible to distinguish their effects. Among women aged 35-44 years, the relative risk estimate decreased with increasing duration of use (p = 0.01). Among women aged 45-59 years, some relative risk estimates were increased, but there was no consistent pattern. The results add to the evidence of an association between oral contraceptive use and an increased risk of breast cancer at young ages.
Two Epstein-Barr virus-related serologic antibody tests in nasopharyngeal carcinoma screening: results from the initial phase of a cluster randomized controlled trial in Southern China.

A nasopharyngeal carcinoma (NPC) mass screening trial using a combination of immunoglobulin A antibodies to Epstein-Barr virus capsid antigen and nuclear antigen-1 by enzyme-linked immunosorbent assay in addition to indirect mirror examination in the nasopharynx and/or lymphatic palpation (IMLP) was conducted in southern China. Cantonese aged 30-59 years residing in 2 cities randomly selected by cluster sampling, Sihui and Zhongshan, were invited to participate in this screening from May 2008 through May 2010. Participants were offered fiberoptic endoscopy examination and/or pathologic biopsy if their serologic tests reached our predefined level of high risk or if results from the physical examination indicated possible cancer (i.e., were IMLP positive). A total of 28,688 individuals were voluntarily screened in the initial round. The overall NPC detection rate was 0.14% (41/28,688) with an early diagnosis rate of 68.3% (28/41) during the first year of follow-up. Thirty-eight of 41 cases (92.7%) were detected among the high-risk group, and 7 of 41 cases (17.1%) were detected among the IMLP-positive group. The 2 Epstein-Barr virus serologic tests by enzyme-linked immunosorbent assay could be a feasible alternative for NPC screening in endemic areas. Further follow-up is needed to examine whether screening has an effect on decreasing mortality from NPC in these areas.
A randomized, double-blind, and placebo-controlled multicenter clinical trial of a novel cytotoxic T-lymphocyte antigen-4 fusion protein, Leining, in Chinese active rheumatoid arthritis patients with an inadequate response to methotrexate

To assess the clinical efficacy as well as safety profiles of Leining, a novel cytotoxic T-lymphocyte antigen-4 fusion protein, versus placebo in the treatment of Chinese active rheumatoid arthritis (RA) patients with an inadequate clinical response to methotrexate (MTX). In this 24-week, randomized, double-blind, placebo-controlled multicenter study, a total of 440 Chinese patients with active RA with an inadequate response to MTX were randomly assigned to receive Leining (10 mg/kg) or placebo. Clinical response was assessed using the American College of Rheumatology 20 % improvement criteria ACR20, ACR50, and ACR70, with ACR20 as the primary major endpoints. Disease activity scores in 28 joints with erythrocyte sedimentation rate assessment (DAS28-ESR) were used to evaluate disease activity. After 24 weeks of treatment, significantly more patients in Leining group achieved ACR20 response than those in placebo group (70.61 vs. 46.36 %; p < 0.001). Similarly, ACR50 and ACR70 responses of Leining group were significantly higher than those of placebo group (40.30 vs. 22.73 %; p < 0.001 and 16.67 vs. 7.27 %; p < 0.05, respectively). DAS28-ESR in Leining group was significantly reduced compared to that in placebo group, with greater clinically meaningful (>1.2 unit) improvement (54.85 vs. 29.09 %, p < 0.05). Both the rates of remission (DAS28-ESR < 2.6) and low disease activity (DAS28-ESR < 3.2) were greater in the Leining group than those in the placebo group (12.42 vs. 2.73 %; p < 0.05 and 15.45 vs. 2.73 %; p < 0.05 respectively). The overall incidence of adverse events was similar in both Leining and placebo groups. No neutralizing antibodies were detected. Leining demonstrated clinically meaningful efficacy compared with placebo in Chinese patients with active RA despite MTX therapy. Administration of Leining in combination with MTX for 24 weeks was well tolerated.
Evaluation of the prognostic significance of HER family mRNA expression in high-risk early breast cancer: a Hellenic Cooperative Oncology Group (HeCOG) validation study

The aim of the study was to evaluate the prognostic ability of the transcriptional profiling of the HER family genes in early breast cancer, as a validation analysis of another previously published HeCOG study. RNA was extracted from 663 formalin-fixed paraffin-embedded (FFPE) tumor tissue samples of high-risk early breast cancer patients enrolled in the randomized HE10/00 trial. Relative mRNA expression of all four HER family members was assessed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). In compliance with our previous study, the overall agreement between qRT-PCR and IHC/FISH for HER2 status determination was good (69%). Likewise, the overall concordance between qRT-PCR and IHC for EGFR status was high (81%). In line with our previously reported data, we demonstrated a positive association between HER2 and HER3 mRNA expression. Similarly, mRNA expression of HER3 and HER4 was positively associated with each other and negatively associated with EGFR. Regarding relationships with clinico-pathological parameters, our findings are also in agreement with our previous results. Generally, increased EGFR and HER2 mRNA expression was related to unfavorable, whereas high HER3 and HER4 mRNA expression was associated with favorable clinico-pathological parameters. In univariate analysis, no significant association between EGFR, HER2 and HER3 mRNA expression and overall survival (OS) or disease-free survival (DFS) was demonstrated. However, high EGFR protein expression was associated with significantly shorter OS (log-rank, p = 0.015). In compliance with our previously published data, increased HER4 mRNA expression had a significantly favorable prognostic value in terms of OS (p = 0.044) and DFS (p = 0.047). In multivariate analysis, among all HER receptors, only EGFR protein expression was found to affect OS (Wald’s p = 0.028) and DFS (p = 0.015) independently. Concerning the combined expression of all four HER family receptors, the combination of high EGFR, high HER2, low HER3 and low HER4 mRNA expression was associated with a trend for shorter OS (log-rank, p = 0.065) and significantly worse DFS (p = 0.033), compared with all other co-expression profiles. These data indicate that qRT-PCR may represent a valid alternative method for evaluating the expression of HER family members in FFPE breast carcinoma tissue samples. Australian New Zealand Clinical Trials Registry ACTRN12609001036202