nils-herrmann/clean_scirepeval huggingface dataset:
An unbiased, staged, multicentre, validation strategy for Alzheimer's disease CSF tau levels

Newly proposed diagnostic criteria for Alzheimer's disease include cerebrospinal fluid (CSF) tau levels as one core supportive criterion. The published high sensitivity and specificity figures for CSF tau levels in Alzheimer's disease are offset by the large range of proposed cutoff values (9.6 pg/mL to 1140 pg/mL). This study aimed to provide guidance on how to establish, validate and audit CSF tau cutoff values using an unbiased, two-stage multicentre strategy. Both receiver operator characteristics (ROC) optimised and population-based cutoff values were calculated on a pilot dataset (n=99), validated in a large dataset (n=560) and then compared to the literature. The data suggest using an ROC optimised cutoff level of 323+/-51.7 pg/mL allowing for the published inter-laboratory coefficient of variation of 16%. This cutoff level was confirmed in a prospective audit (n=100). As demand for CSF tau levels will increase globally, the accuracy of local CSF hTau cutoff levels can be compared against this benchmark.
A novel intra-operative, high-resolution atrial mapping approach

A new technique is demonstrated for extensive high-resolution intra-operative atrial mapping that will facilitate the localization of atrial fibrillation (AF) sources and identification of the substrate perpetuating AF. Prior to the start of extra-corporal circulation, a 8 × 24-electrode array (2-mm inter-electrode distance) is placed subsequently on all the right and left epicardial atrial sites, including Bachmann’s bundle, for recording of unipolar electrograms during sinus rhythm and (induced) AF. AF is induced by high-frequency pacing at the right atrial free wall. A pacemaker wire stitched to the right atrium serves as a reference signal. The indifferent pole is connected to a steal wire fixed to subcutaneous tissue. Electrograms are recorded by a computerized mapping system and, after amplification (gain 1000), filtering (bandwidth 0.5–400 Hz), sampling (1 kHz) and analogue to digital conversion (16 bits), automatically stored on hard disk. During the mapping procedure, real-time visualization secures electrogram quality. Analysis will be performed offline. This technique was performed in 168 patients of 18 years and older, with coronary and/or structural heart disease, with or without AF, electively scheduled for cardiac surgery and a ventricular ejection fraction above 40 %. The mean duration of the entire mapping procedure including preparation time was 9 ± 2 min. Complications related to the mapping procedure during or after cardiac surgery were not observed. We introduce the first epicardial atrial mapping approach with a high resolution of ≥1728 recording sites which can be performed in a procedure time of only 9±2 mins. This mapping technique can potentially identify areas responsible for initiation and persistence of AF and hopefully can individualize both diagnosis and therapy of AF.
A prospective, double-blind, randomized controlled trial of the angiotensin-converting enzyme inhibitor Ramipril In Aortic Stenosis (RIAS trial)

Angiotensin-converting enzyme (ACE) inhibitors improve left ventricular (LV) remodelling and outcome in heart failure and hypertensive heart disease. They may be similarly beneficial in patients with aortic stenosis (AS), but historical safety concerns have limited their use, and no prospective clinical trials exist.



We conducted a prospective, randomized, double-blind, placebo-controlled trial in 100 patients with moderate or severe asymptomatic AS to examine the physiological effects of ramipril, particularly LV mass (LVM) regression. Subjects were randomized to ramipril 10 mg daily (n = 50) or placebo (n = 50) for 1 year, and underwent cardiac magnetic resonance, echocardiography, and exercise testing at 0, 6, and 12 months, with follow-up data available in 77 patients. There was a modest but progressive reduction in LVM (the primary end point) in the ramipril group vs. the placebo group (mean change -3.9 vs. +4.5 g, respectively, P = 0.0057). There were also trends towards improvements in myocardial physiology: the ramipril group showed preserved tissue Doppler systolic velocity compared with placebo (+0.0 vs. -0.5 cm/s, P = 0.04), and a slower rate of progression of the AS (valve area 0.0 cm(2) in the ramipril group vs. -0.2 cm(2) in the placebo arm, P = 0.067). There were no significant differences in major adverse cardiac events.



ACE inhibition leads to a modest, but progressive reduction in LVM in asymptomatic patients with moderate-severe AS compared with placebo, with trends towards improvements in myocardial physiology and slower progression of valvular stenosis. A larger clinical outcome trial to confirm these findings and explore their clinical relevance is required.
Dietary intake and risk of rheumatoid arthritis—a cross section multicenter study

Environmental factors play an important role in the development of rheumatoid arthritis (RA). Among these factors, smoking is generally considered to be an established risk factor for RA. Data regarding the impact of diet on risk of RA development is limited. This study assessed the impact of dietary patterns on RA susceptibility in Chinese populations. This was a large scale, case-control study composed of 968 patients with RA and 1037 matched healthy controls. Subjects were recruited from 18 teaching hospitals. Socio-demographic characteristics and dietary intakes 5 years prior to the onset of RA were reported by a self-administered questionnaire. Differences in quantity of consumption between cases and controls were analyzed by Student’s t test. Multiple logistic regression analysis was applied to identify independent dietary risk factor(s) responsible for RA susceptibility. Compared to healthy individuals, RA patients had decreased consumption of mushrooms (P = 0.000), beans (P = 0.006), citrus (P = 0.000), poultry (P = 0.000), fish (P = 0.000), edible viscera (P = 0.018), and dairy products (P = 0.005). Multivariate analyses revealed that several dietary items may have protective effects on RA development, such as mushrooms (aOR = 0.669; 95%CI = 0.518–0.864, P = 0.002), citrus fruits (aOR = 0.990; 95%CI = 0.981–0.999, P = 0.04), and dairy products (aOR = 0.921; 95%CI 0.867–0.977, P = 0.006). Several dietary factors had independent effects on RA susceptibility. Dietary interventions may reduce the risk of RA.
A novel inhibitor of active protein kinase G attenuates chronic inflammatory and osteoarthritic pain

Activating PKG-1α induces a long-term hyperexcitability (LTH) in nociceptive neurons. Since the LTH correlates directly with chronic pain in many animal models, we tested the hypothesis that inhibiting PKG-1α would attenuate LTH-mediated pain. We first synthesized and characterized compound N46 (N-((3R,4R)-4-(4-(2-fluoro-3-methoxy-6-propoxybenzoyl)benzamido)pyrrolidin-3-yl)-1H-indazole-5-carboxamide). N46 inhibits PKG-1α with an IC50 of 7.5 nmol, was highly selective when tested against a panel of 274 kinases, and tissue distribution studies indicate that it does not enter the CNS. To evaluate its antinociceptive potential, we used 2 animal models in which the pain involves both activated PKG-1α and LTH. Injecting complete Freund's adjuvant (CFA) into the rat hind paw causes a thermal hyperalgesia that was significantly attenuated 24 hours after a single intravenous injection of N46. Next, we used a rat model of osteoarthritic knee joint pain and found that a single intra-articular injection of N46 alleviated the pain 14 days after the pain was established and the relief lasted for 7 days. Thermal hyperalgesia and osteoarthritic pain are also associated with the activation of the capsaicin-activated transient receptor protein vanilloid-1 (TRPV1) channel. We show that capsaicin activates PKG-1α in nerves and that a subcutaneous delivery of N46 attenuated the mechanical and thermal hypersensitivity elicited by exposure to capsaicin. Thus, PKG-1α appears to be downstream of the transient receptor protein vanilloid-1. Our studies provide proof of concept in animal models that a PKG-1α antagonist has a powerful antinociceptive effect on persistent, already existing inflammatory pain. They further suggest that N46 is a valid chemotype for the further development of such antagonists.
Development of a servo-controller of heart rate using a cycle ergometer

In exercise training, precise control of exercise intensity would maximize the training efficacy while minimizing risks. To adjust work rate, heart rate (HR) has been used as a measure of exercise intensity. Thus, we developed a servo-controller of HR using a cycle ergometer. After estimating the transfer function from work rate to HR, we optimized feedback parameters for achieving a quick and stable HR response by means of a computer simulation. We then examined the performance of the servo-controller of HR in 55 healthy volunteers. We set the target HR at 60% and 75% of the age-predicted maximum HR. Times required for HR to reach 90% of the target HR were 136 ± 33 and 137 ± 22s in the respective protocols. Standard deviations of the steady-state difference between the target and measured HRs were 2.5 ± 0.6 and 3.8 ± 1.1 beats/min. We conclude that the developed servo-controller makes it possible to precisely regulate HR and, thereby, exercise intensity.
Comparative analysis between dextran sulfate adsorption and direct adsorption of lipoproteins in their capability to reduce erythrocyte adhesiveness/aggregation in the peripheral blood.

The purpose of this study was to compare the degree of erythrocyte adhesiveness/aggregation (EAA) reduction of two low-density lipoprotein (LDL) apheretic procedures, namely direct adsorption of lipoproteins (DALI) and dextran sulfate adsorption (DSA). A significant (P < 0.001) reduction of EAA was noted in six hypercholesterolemic patients who underwent a total of 40 apheretic sessions and no difference was noted in the degree of EAA reduction by the two techniques. Thus. being a real-time and point-of-care test, the erythrocyte adhesiveness/aggregation test can be applied in relevant situations of acute ischemia, where therapeutic LDL apheresis could improve the hemorheology of individuals with increased concentrations of cholesterol and inflammatory sensitive proteins.
Repetitive bilateral arm training and motor cortex activation in chronic stroke: a randomized controlled trial.

Reorganization in central motor networks occurs during early recovery from hemiparetic stroke. In chronic stroke survivors, specific rehabilitation therapy can improve upper extremity function.



To test the hypothesis that in patients who have chronic motor impairment following stroke, specific rehabilitation therapy that improves arm function is associated with reorganization of cortical networks.



A randomized controlled clinical trial conducted in a US ambulatory rehabilitation program with 21 patients (median [IQR], 50.3 [34.8-77.3] months after unilateral stroke). Data were collected between 2001 and 2004.



Patients were randomly assigned to bilateral arm training with rhythmic auditory cueing (BATRAC) (n = 9) or standardized dose-matched therapeutic exercises (DMTE) (n = 12). Both were conducted for 1 hour, 3 times a week, for 6 weeks.



Within 2 weeks before and after the intervention, brain activation during elbow movement assessed by functional magnetic resonance imaging (fMRI) and functional outcome assessed using arm function scores.



Patients in the BATRAC group but not in the DMTE group increased hemispheric activation during paretic arm movement (P = .03). Changes in activation were observed in the contralesional cerebrum and ipsilesional cerebellum (P = .009). BATRAC was associated with significant increases in activation in precentral (P<.001) and postcentral gyri (P = .03) and the cerebellum (P<.001), although 3 BATRAC patients showed no fMRI changes. Considering all patients, there were no differences in functional outcome between groups. When only BATRAC patients with fMRI response were included (n = 6), BATRAC improved arm function more than DMTE did (P = .02).



These preliminary findings suggest that BATRAC induces reorganization in contralesional motor networks and provide biological plausibility for repetitive bilateral training as a potential therapy for upper extremity rehabilitation in hemiparetic stroke.
Half-molar sodium lactate infusion improves cardiac performance in acute heart failure: a pilot randomised controlled clinical trial

Acute heart failure (AHF) is characterized by inadequate cardiac output (CO), congestive symptoms, poor peripheral perfusion and end-organ dysfunction. Treatment often includes a combination of diuretics, oxygen, positive pressure ventilation, inotropes and vasodilators or vasopressors. Lactate is a marker of illness severity but is also an important metabolic substrate for the myocardium at rest and during stress. We tested the effects of half-molar sodium lactate infusion on cardiac performance in AHF.



We conducted a prospective, randomised, controlled, open-label, pilot clinical trial in 40 patients fulfilling two of the following three criteria for AHF: (1) left ventricular ejection fraction <40%, (2) acute pulmonary oedema or respiratory failure of predominantly cardiac origin requiring mechanical ventilation and (3) currently receiving vasopressor and/or inotropic support. Patients in the intervention group received a 3 ml/kg bolus of half-molar sodium lactate over the course of 15 minutes followed by 1 ml/kg/h continuous infusion for 24 hours. The control group received only a 3 ml/kg bolus of Hartmann's solution without continuous infusion. The primary outcome was CO assessed by transthoracic echocardiography 24 hours after randomisation. Secondary outcomes included a measure of right ventricular systolic function (tricuspid annular plane systolic excursion (TAPSE)), acid-base balance, electrolyte and organ function parameters, along with length of stay and mortality.



The infusion of half-molar sodium lactate increased (mean ± SD) CO from 4.05 ± 1.37 L/min to 5.49 ± 1.9 L/min (P < 0.01) and TAPSE from 14.7 ± 5.5 mm to 18.3 ± 7 mm (P = 0.02). Plasma sodium and pH increased (136 ± 4 to 146 ± 6 and 7.40 ± 0.06 to 7.53 ± 0.03, respectively; both P < 0.01), but potassium, chloride and phosphate levels decreased. There were no significant differences in the need for vasoactive therapy, respiratory support, renal or liver function tests, duration of ICU and hospital stay or 28- and 90-day mortality.



Infusion of half-molar sodium lactate improved cardiac performance and led to metabolic alkalosis in AHF patients without any detrimental effects on organ function.
Learning and support preferences of adult patients with cancer at a comprehensive cancer center.

To identify content items for an inclusive education curriculum for adult patients with cancer, as well as describe their learning and support preferences, determine the level of information provided to them, and assess the patients' interest in potential new services.



Exploratory, descriptive survey research.



A National Cancer Institute-designated Comprehensive Cancer Center.


SAMPLE
All consenting adult patients with cancer who had appointments in the outpatient care setting during a two-week period (N = 1,310).



A 3-phase study identified core components of an inclusive educational curriculum, conducted structured interviews of patients with cancer, and validated findings in a selected sample.



The surveys were completed and returned by 48% (n = 625) of the patients. The most favored method for learning about all cancer topics was discussions with physicians (66%). Other preferred methods included brochures or booklets provided by physicians or nurses (33%), discussions with nurses (34%), self-selecting print media from information displays (20%), and talking with other patients with cancer (14%). Statistically significant differences in learning preferences were found among subgroups defined by age, gender, and education.



Patients preferred interactive, interpersonal communication with physicians or nurses. In addition, the prevailing method of education delivery for patients with cancer was providing print materials that support and enhance knowledge shared in the patient-healthcare team communication.



This study confirms the importance of the learning and support preferences of patients with cancer. To implement a successful education program for their patients, nurses must be aware of patients' preferences for learning new information. Time must be set aside for one-on-one communication with patients, and print materials must be easily accessible to healthcare providers to support the patient-education process.
Permutation test for groups of scanpaths using normalized Levenshtein distances and application in NMR questions

This paper presents a permutation test that statistically compares two groups of scanpaths. The test uses normalized Levenshtein distances when the lengths of scanpaths are not the same. This method was applied in a recent eye-tracking experiment in which two groups of chemistry students viewed nuclear magnetic resonance (NMR) spectroscopic signals and chose the corresponding molecular structure from the candidates. A significant difference was detected between the two groups, which is consistent with the fact that students in the expert group showed more efficient scan patterns in the experiment than the novice group. Various numbers of permutations were tested and the results showed that p-values only varied in a small range with different permutation numbers and that the statistical significance was not affected.
Recruitment of black women with type 2 diabetes into a self-management intervention trial.

The purpose of this study was to evaluate the relationship of recruitment methods to enrollment status in Black women with type 2 diabetes screened for entry into a randomized clinical trial (RCT). Using a cross-sectional study design with convenience sampling procedures, data were collected on recruitment methods to which the women responded (N=236). Results demonstrated that the RCT had a moderate overall recruitment rate of 46% and achieved only 84% of its projected accrual goal (N=109). Chi-square analysis demonstrated that enrollment outcomes varied significantly according to recruitment methods (P=.05). Recruitment methods such as community health fairs (77.8%), private practice referrals (75.0%), participant referrals (61.5%), community clinic referrals (44.6%), community advertising and marketing (40.9%), and chart review (40.4%) demonstrated variable enrollment yields. Results confirm previous findings that indicate that Black Americans may be successfully recruited into research studies at moderate rates when traditional recruitment methods are enhanced and integrated with more culturally sensitive methods. Lessons learned are considered.
Real-life results of balloon kyphoplasty for vertebral compression fractures from the SWISSspine registry.

The Swiss Federal Office of Public Health mandated a nationwide health technology assessment-registry for balloon kyphoplasty (BKP) for decision making on reimbursement of these interventions. The early results of the registry led to a permanent coverage of BKP by basic health insurance. The documentation was continued for further evidence generation.



This analysis reports on the 1 year results of patients after BKP treatment.



Prospective multicenter observational case series.


PATIENT SAMPLE
The data on 625 cases with 819 treated vertebrae were documented from March 2005 to May 2012.



Surgeon-administered outcome instruments were primary intervention form for BKP and the follow-up form; patient self-reported measures were EuroQol-5D questionnaire, North American Spine Society outcome instrument /Core Outcome Measures Index (including visual analog scale), and a comorbidity questionnaire. Outcome measures were back pain, medication, quality of life (QoL), cement extrusions, and new fractures within the first postoperative year.



Data were recorded preoperatively and at 3 to 6-month and 1-year follow-ups. Wilcoxon signed-rank test was used for comparison of pre- with postoperative measurements. Multivariate logistic regression was used to identify factors with a significant influence on the outcome.



Seventy percent of patients were women with mean age of 71 years (range, 18-91 years); mean age of men was 65 years (range, 15-93 years). Significant and clinically relevant reduction of back pain, improvement of QoL, and reduction of pain killer consumption was seen within the first postoperative year. Preoperative back pain decreased from 69.3 to 29.0 at 3 to 6-month and remained unchanged at 1-year follow-ups. Consequently, QoL improved from 0.23 to 0.71 and 0.75 at the same follow-up intervals. The overall vertebra-based cement extrusion rates with and without extrusions into intervertebral discs were 22.1% and 15.3%, respectively. Symptomatic cement extrusions with radiculopathy were five (0.8%). A new vertebral fracture within a year from the BKP surgery was observed in 18.4% of the patients.



The results of the largest observational study for BKP so far are consistent with published randomized trials and systematic reviews. In this routine health care setting, BKP is safe and effective in reducing pain, improving QoL, and lowering pain_killer consumption and has an acceptable rate of cement extrusions. Postoperative outcome results show clear and significant clinical improvement at early follow-up that remain stable during the first postoperative year.
Pharmacological constriction of the lower oesophageal sphincter: a simple method of arresting variceal haemorrhage.

The effect of pharmacological constriction of the lower oesophageal sphincter (LOS) on oesophageal varices was investigated in an experimental study followed by a controlled clinical trial. In the experimental study intravariceal pressure was measured just above the LOS in 11 patients before and after constricting the LOS by intravenous pentagastrin. Intravariceal pressure fell from a mean of 23 (range 12-36) mmHg to 4 (range 0-7) mmHg (p less than 0.001). This marked pressure drop indicated the considerable compression of varices that occurred within the LOS. A prospective controlled clinical trial examined whether LOS constriction (effected by the longer acting metoclopramide) would compress varices sufficiently to arrest active variceal bleeding originating from the lowest 2 cm oesophagus--the area encircled by the LOS. Of 11 patients who received metoclopramide, 10 stopped bleeding compared with four of the 11 who received placebo (p less than 0.01). Pharmacological constriction of the LOS appears to offer a new and effective approach for arresting active bleeding from oesophageal varices.