nils-herrmann/clean_scirepeval huggingface dataset:
Bitolterol mesylate (WIN 32784) aerosol. A new long-acting bronchodilator with reduced chronotropic effects.

Bitolterol mesylate (WIN 37284) is alpha-[tert-butylaminomethyl]-3,4-dihydroxybenzyl alcohol 3,4-di(p-toluate) methanesulfonate, a diester sympathomimetic amine bronchodilator. Bitolterol mesylate represents a new concept in sympathomimetic amine therapy. It is "prodrug" which is inactive until altered in the body. The intact 3,4-diester molecule is metabolized by esterase hydrolysis to release the active catecholamine, N-t-butylarterenol. Because the level of esterase is greater in the pulmonary tissue than in the heart, bitolterol mesylate aerosol was shown to be an effective bronchodilator drug, without any significant cardic side effects. The onset of action was rapid and lasted more than six hours. The improvement over baseline values in the forced expiratory volume in the first second and the mean forced expiratory flow during the middle half of the forced vital capacity was greater than 15 percent and 30 percent, respectively.
The von Willebrand inhibitor ARC1779 reduces cerebral embolization after carotid endarterectomy: a randomized trial.

Inhibition of von Willebrand factor offers a novel approach to prevention of stroke and myocardial ischemia but has not yet been demonstrated to show efficacy on clinically relevant end points. ARC1779 is an aptamer that inhibits the prothrombotic function of von Willebrand factor by binding to the A1 domain of von Willebrand factor and thereby blocking its interaction with glycoprotein. Phase 1 studies suggest it inhibits platelet aggregation with less increase in bleeding than conventional antiplatelet agents. The effect of ARC 1779 on cerebral emboli immediately after carotid endarterectomy was investigated in a randomized clinical trial.



Patients undergoing carotid endarterectomy were randomized double-blind to ARC1779 or placebo administered intravenously. Transcranial Doppler recording, to detect cerebral embolic signals, was performed in the first 3 hours postoperatively. The primary end point was time to first embolic signals.



Thirty-six patients were recruited, 18 in each arm. The Kaplan-Meier median time to first embolic signals was 83.6 minutes for ARC1779 compared with 5.5 minutes for placebo. Using Cox proportional hazards embolic signals occurred statistically significantly later on ARC1779 (P=0.007). Reduced embolic signals counts were correlated with inhibition of von Willebrand factor activity (P=0.03). Increased perioperative bleeding and anemia were seen with ARC1779.



von Willebrand factor inhibition reduces thromboembolism in humans. It may play a role in treatment of stroke and myocardial ischemia. The extent to which bleeding complications occur in nonoperated patients needs to be assessed in further studies.
A cluster-randomized trial of provider-initiated (opt-out) HIV counseling and testing of tuberculosis patients in South Africa.

To determine whether implementation of provider-initiated human immunodeficiency virus (HIV) counseling would increase the proportion of tuberculosis (TB) patients who received HIV counseling and testing.



Cluster-randomized trial with clinic as the unit of randomization.



Twenty, medium-sized primary care TB clinics in the Nelson Mandela Metropolitan Municipality, Port Elizabeth, Eastern Cape Province, South Africa.



A total of 754 adults (18 years and older) newly registered as TB patients in the 20 study clinics.



Implementation of provider-initiated HIV counseling and testing.



Percentage of TB patients HIV counseled and tested.  Percentage of patients with HIV test positive, and percentage of those who received cotrimoxazole and who were referred for HIV care.



: A total of 754 adults newly registered as TB patients were enrolled. In clinics randomly assigned to implement provider-initiated HIV counseling and testing, 20.7% (73/352) patients were counseled versus 7.7% (31/402) in the control clinics (P = 0.011), and 20.2% (n = 71) versus 6.5% (n = 26) underwent HIV testing (P = 0.009). Of those patients counseled, 97% in the intervention clinics accepted testing versus 79% in control clinics (P = 0.12). The proportion of patients identified as HIV infected in intervention clinics was 8.5% versus 2.5% in control clinics (P = 0.044). Fewer than 40% of patients with a positive HIV test were prescribed cotrimoxazole or referred for HIV care in either study arm.



Provider-initiated HIV counseling significantly increased the proportion of adult TB patients who received HIV counseling and testing, but the magnitude of the effect was small. Additional interventions to optimize HIV testing for TB patients urgently need to be evaluated.
The effectiveness of esomeprazole 40 mg in patients with persistent symptoms of gastro-oesophageal reflux disease following treatment with a full dose proton pump inhibitor

Some patients with gastro-oesophageal reflux disease (GORD) remain symptomatic despite proton pump inhibitor (PPI) treatment. There is a need to determine the most appropriate management of these patients.



To assess the effectiveness of esomeprazole 40 mg in GORD symptoms persisting in patients receiving a full daily dose PPI.



In this multi-centre open label study patients who had received full daily dose PPI for 8 weeks, but were still experiencing persistent GORD symptoms, were treated with esomeprazole 40 mg for 8 weeks (n = 99). The primary outcome variable was the change in the frequency of heartburn. Patient-reported outcomes were also assessed using the Reflux Disease Questionnaire (RDQ) and the GORD Impact Scale (GIS).



The mean frequency of heartburn was reduced by 78% from 4.4 days a week to 1 day a week at the end of the 8-week treatment period (p < 0.0001). Other GORD symptoms were also significantly reduced following of treatment with esomeprazole (all p < 0.0001). All RDQ dimensions and the level of symptom control as measured by the GIS also showed significant improvement at 8 weeks.



In patients with persistent GORD symptoms despite full dose daily PPI therapy, esomeprazole 40 mg significantly improved the frequency and severity of all GORD symptoms.
Sleep, arousal and health-related quality of life in men and women with coronary artery disease.

To evaluate whether there are gender differences in insomnia, sleep quality, sleep efficiency (%), general arousal, disease-specific and health-related quality of life in patients with coronary artery disease, compared with an age- and gender-matched randomly selected group from the general population.



There are gender difference effects of sleep disturbances in the general population, but this perspective among patients with coronary artery disease has been poorly analysed.



In this prospective study, comparative, descriptive and model testing designs were used.



The patients with coronary artery disease, 556 men and 324 women aged 25-86, were compared with a matched population-based group. Data were collected by validated and reliability-tested questionnaires.



The prevalence of severe insomnia varied between 17-44% in all four groups. The severe insomniac coronary artery disease patients displayed a two- or threefold higher presleep arousal, had two hours shorter nocturnal sleep duration/night and were more limited in their physical exercise level than the population-based group. Gender differences in sleep quality, sleep efficiency (%) and general arousal disappeared with increased insomnia severity.



Independent of gender, age and comorbidity, physical exercise, general arousal behaviour and delayed poststress recovery after mental stress were found to have a negative impact on the coronary artery disease patients' sleep quality and sleep efficiency (%), interfering with their health-related quality of life. The variables significantly explained 41% of the sleep quality outcome and 29% of the sleep efficiency (%).


 TO CLINICAL PRACTICE
Insomnia because of hyperarousal behaviour can be an important factor in the development of an individual self-care management programme supported by a healthcare team.
Biochemical, pharmacological, and phase I clinical evaluation of pseudoisocytidine.

Pseudoisocytidine (psi ICyd) is a C-nucleoside with enhanced stability and resistance to enzymatic deamination when compared to 5-azacytidine and 1-beta-D-arabinofuranosylcytosine. Elimination kinetics in plasma using [14C]psi ICyd showed a beta-phase for t1/2 for 14C of 2 hr and a beta-phase t1/2 of unchanged psi ICyd of 1.5 hr. Net recovery of radioactivity in urine over 24 hr varied between 40 and 80% of the administered dose; 50 to 90% was unchanged drug and the rest was pseudouridine. Human leukemic cells in vitro deaminated psi ICyd very slowly, formed appreciable quantities of pseudoisocytidine triphosphate, and incorporated small amounts into RNA and DNA. Clinical trials were done using a daily i.v. injection for 5 consecutive days. Hematological or intestine toxicities were not seen, nor was depression of white blood cell count observed in leukemic patients. Hepatic toxicity proved to be dose limiting; this was characterized by an early phase with elevation of prothrombin time and aspartate aminotransferase. A later phase with cirrhosis was observed in two patients. Autopsy showed massive hepatic necrosis in patients dying of acute toxicity and micronodular cirrhosis in one patient dying with the chronic form.
Minimum requirements for accurate and efficient real-time on-chip spike sorting

Extracellular recordings are performed by inserting electrodes in the brain, relaying the signals to external power-demanding devices, where spikes are detected and sorted in order to identify the firing activity of different putative neurons. A main caveat of these recordings is the necessity of wires passing through the scalp and skin in order to connect intracortical electrodes to external amplifiers. The aim of this paper is to evaluate the feasibility of an implantable platform (i.e., a chip) with the capability to wirelessly transmit the neural signals and perform real-time on-site spike sorting.


NEW METHOD
We computationally modelled a two-stage implementation for online, robust, and efficient spike sorting. In the first stage, spikes are detected on-chip and streamed to an external computer where mean templates are created and sent back to the chip. In the second stage, spikes are sorted in real-time through template matching.



We evaluated this procedure using realistic simulations of extracellular recordings and describe a set of specifications that optimise performance while keeping to a minimum the signal requirements and the complexity of the calculations.


COMPARISON WITH EXISTING 
A key bottleneck for the development of long-term BMIs is to find an inexpensive method for real-time spike sorting. Here, we simulated a solution to this problem that uses both offline and online processing of the data.



Hardware implementations of this method therefore enable low-power long-term wireless transmission of multiple site extracellular recordings, with application to wireless BMIs or closed-loop stimulation designs.
Geographic and educational factors and risk of the first peritonitis episode in Brazilian Peritoneal Dialysis study (BRAZPD) patients.

Peritonitis remains as the most frequent cause of peritoneal dialysis (PD) failure, impairing patient's outcome. No large multicenter study has addressed socioeconomic, educational, and geographic issues as peritonitis risk factors in countries with a large geographic area and diverse socioeconomic conditions, such as Brazil.



Incident PD patients recruited from 114 dialysis centers and reporting to BRAZPD, a multicenter observational study, from December 2004 through October 2007 were included. Clinical, dialysis-related, demographic, and socioeconomic variables were analyzed. Patients were followed up until their first peritonitis. Cox proportional model was used to determine independent factors associated with peritonitis.



In a cumulative follow-up of 2032 patients during 22.026 patient-months, 474 (23.3%) presented a first peritonitis episode. In contrast to earlier findings, PD modality, previous hemodialysis, diabetes, gender, age, and family income were not risk predictors. Factors independently associated with increased hazard risk were lower educational level, non-white race, region where patients live, shorter distance from dialysis center, and lower number of patients per center.



Educational level and geographic factors as well as race and center size are associated with risk for the first peritonitis, independent of socioeconomic status, PD modality, and comorbidities.
CMTM4 is frequently downregulated and functions as a tumour suppressor in clear cell renal cell carcinoma

Chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family (CMTM) is a gene family involved in multiple malignancies. CMTM4 is a member of this family and is located at chromosome 16q22.1, a locus that harbours a number of tumour suppressor genes. It has been defined as a regulator of cell cycle and division in HeLa cells; however, its roles in tumourigenesis remain poorly studied.



An integrated bioinformatics analysis based on the array data from the GEO database was conducted to view the differential expression of CMTM4 across multiple cancers and their corresponding control tissues. Primary clear cell renal cell carcinoma (ccRCC) and the paired adjacent non-tumour tissues were then collected to examine the expression of CMTM4 by western blotting, immunohistochemistry, and quantitative RT-PCR. The ccRCC cell lines A498 and 786-O and the normal renal tubular epithelial cell line HK-2 were also tested for CMTM4 expression by western blotting. Cell Counting Kit-8 (CCK-8) and viable cell counting assays were used to delineate the growth curves of 786-O cells after CMTM4 overexpression or knockdown. Wound healing and transwell assays were performed to assess the cells' ability to migrate. The effects of CMTM4 on cellular apoptosis and cell cycle progression were analysed by flow cytometry, and cell cycle hallmarks were detected by western blotting and RT-PCR. The xenograft model in nude mice was used to elucidate the function of CMTM4 in tumourigenesis ex vivo.



By omic data analysis, we found a substantial downregulation of CMTM4 in ccRCC. Western blotting then confirmed that CMTM4 was dramatically reduced in 86.9 % (53/61) of ccRCC tissues compared with the paired adjacent non-tumour tissues, as well as in the 786-O and A498 ccRCC cell lines. Restoration of CMTM4 significantly suppressed 786-O cell growth by inducing G2/M cell cycle arrest and p21 upregulation, and cell migration was also inhibited. However, knockdown of CMTM4 led to a completely opposite effect on these cell behaviours. Overexpression of CMTM4 also markedly inhibited the tumour xenograft growth in nude mice.



CMTM4 is downregulated and exhibits tumour-suppressor activities in ccRCC, and could be exploited as a target for ccRCC treatment.
Spatial distribution and temporal changes of pulmonary thallium uptake in myocardial perfusion studies

Spatial distribution and temporal changes in pulmonary thallium uptake were assessed in 24 normal subjects and 35 patients with coronary artery disease (CAD). In studies carried out directly after stress and 3 h later, pulmonary T1 uptake was assessed as body surface area corrected absolute pulmonary uptake in the upper, middle and lower right lung regions, and in the total right lung and upper left lung. Pulmonary/myocardial (PM) uptake ratios for these 5 regions were calculated as mean pulmonary/mean background-corrected myocardial uptake. Additionally, wash-out was assessed for each region and for the myocardium. In normal subjects, the inital pulmonary T1 uptake, the PM ratios and T1 wash-out were greater in the lower lung regions than in the upper. In the late studies, no significant differences in T1 content or PM ratios were found among the regions. In patients with CAD, initial pulmonary T1 uptake and PM ratios were greater in the lower than in the upper regions, and higher than for the normal subjects in all pulmonary regions (P<0.001). T1 wash-out was significantly higher in the low and middle regions versus the upper region (P < 0.001) and higher in all regions than in normal subjects (P<0.001). In the late studies no significant differences in T1 content or PM ratios were found between any pulmonary regions. Pulmonary T1 content was, in all regions, higher in CAD than in normal subjects (P<0.01), as were the PM ratios (P<0.001). In conclusion, in normal subjects as well as in patients with CAD, pulmonary T1 uptake is greatest in the lower lung regions. Absolute pulmonary T1 uptake, PM ratios and pulmonary wash-out are greater in all lung regions in patients with CAD. Lower myocardial uptake may be the more important factor in producing the increased PM ratios in patients with CAD. Pulmonary redistribution is complete after 3–4 h. These characteristics strongly affect pulmonary T1 uptake ratios and wash-out assessments.
Development and validation of a highly sensitive LC-ESI-MS/MS method for the determination of Orteronel® (TAK-700) in rat plasma: application to a pharmacokinetic study.

A highly sensitive, specific and high-throughput LC-ESI-MS/MS method in the positive mode has been developed and validated for the quantitation of Orteronel® (TAK-700) in rat plasma using YM-55208 as an internal standard.



The assay procedure involves extraction of Orteronel and internal standard from rat plasma with liquid-liquid extraction method. Chromatographic separation was achieved using an isocratic mobile phase at a flow rate of 0.6 ml/min on an Atlantis dC18 column with a total run time of 2.5 min. The MS/MS ion transitions monitored were m/z 308.4→95.0 for Orteronel and m/z 262.3→194.2 for IS. Method validation was performed as per US FDA guidelines. The LLOQ achieved was 0.42 ng/ml and the linearity range extended from 0.42 to 814 ng/ml.



The results met the acceptance criteria. The validated method was successfully applied to characterize the pharmacokinetic parameters of Orteronel in rat plasma.
Design and initial enrollment in the Vascular Physicians Offer and Report (VAPOR) trial.

Although patient smoking cessation is a key priority for vascular surgeons, significant variation exists in the manner in which vascular surgeons address this key process of care. We describe a multicenter, cluster-randomized trial that compares a standardized, brief smoking cessation intervention to usual care for patients facing vascular surgery or endovascular interventions. Eight centers were randomized to provide usual care for smoking cessation or a standardized protocol consisting of (1) physician "very brief advice" to stop smoking, (2) offering nicotine replacement therapy, and (3) referral to a phone-based counseling service. Trial enrollment began on September 1, 2014. At present, 142 patients had been enrolled in the trial across eight sites. Compared with patients in the usual care arm, patients enrolled in the smoking cessation intervention arm were more likely to receive physician advice (98% vs 77%), a prescription for nicotine replacement therapy (77% vs 13%), and quitline referral (93% vs 33%; all P < .001). Although final results of the intervention on smoking cessation rates are still forthcoming, surgeon delivery of a brief, evidence-based smoking cessation intervention appears feasible for patients facing invasive vascular care.
The effects of Internet-based home training on upper limb function in adults with cerebral palsy.

While adults with hemiplegic cerebral palsy (CP) can have significant upper limb dysfunction, the effects of movement-based training has not been investigated.



This uncontrolled trial assessed the effects of a home and internet-based upper limb intervention program targeting motor and sensory function.



Twelve adults, aged 21 to 57 yrs, GMFCS levels I-III with asymmetric upper limb involvement participated in the Upper Limb Training and Assessment (ULTrA) program. Clinical and functional measures included the Motor Activity Log (MAL), the Nine-Hole Peg test, and grip strength. An upper limb training system consisting of a laptop, webcam, target light board, and hand manipulation/ discrimination devices was installed in each participant's home. Training occurred 40 min/day, 5 days/wk for 8 wks and included both unilateral and bilateral reach movements as well as a series of hand sensorimotor tasks such as card turning, stereognosis, and tactile discrimination. Data generated during each session were transmitted to the laboratory via the Internet.



were movement time, interlimb delay time, and performance on hand sensorimotor tasks.



Following training, affected limb reach movement time decreased significantly for unilateral and bilateral tasks. Interlimb delay during sequential reaching also decreased. Significant improvement in hand manipulation tasks was also seen. Compliance was excellent and there were no adverse effects.



The ULTrA program had beneficial effects for adults with CP and is safe and convenient to use. This system contrasts sharply with programs with similar intent that require participant travel and hours of therapist-based intervention.
Efficacy of salmeterol xinafoate in the treatment of COPD.

To examine and compare the efficacy and safety of salmeterol xinafoate, a long-acting inhaled beta2-adrenergic agonist, with inhaled ipratropium bromide and inhaled placebo in patients with COPD.



A stratified, randomized, double-blind, double-dummy, placebo-controlled, parallel group clinical trial.



Multiple sites at clinics and university medical centers throughout the United States.



Four hundred eleven symptomatic patients with COPD with FEV1 < or = 65% predicted and no clinically significant concurrent disease.



Comparison of inhaled salmeterol (42 microg twice daily), inhaled ipratropium bromide (36 microg four times a day), and inhaled placebo (2 puffs four times a day) over 12 weeks.



Salmeterol xinafoate was significantly (p < 0.0001) better than placebo and ipratropium in improving lung function at the recommended doses over the 12-week trial. Both salmeterol and ipratropium reduced dyspnea related to activities of daily living compared with placebo; this improvement was associated with reduced use of supplemental albuterol. Analyses of time to first COPD exacerbation revealed salmeterol to be superior to placebo and ipratropium (p < 0.05). Adverse effects were similar among the three treatments.



These collective data support the use of salmeterol as first-line bronchodilator therapy for the long-term treatment of airflow obstruction in patients with COPD.
Effects of piracetam on regional cerebral blood flow and mental functions in patients with organic dementia

The effects of piracetam (Nootropil®, UCB 6215) on mental functions and on regional cerebral blood flow (rCBF) were investigated in eight patients in the presenile age who displayed symptoms of moderate dementia. The double-blind crossover design included nine measurement occasions, each involving rCBF measurement by the 133-Xe inhalation method, ratings of symptoms of dementia, personality changes, and side effects, and a psychometric investigation. Three investigations were included in each of three treatment periods. The first investigation in a period was made without medication. Then either placebo or piracetam 4.8 g/day or 9.6 g/day was given during four weeks with measurements after 2 weeks and 4 weeks. There were intervals of 4 weeks without medication between the treatment periods. Piracetam had no significant effect on either mental functions or rCBF.