nils-herrmann/clean_scirepeval huggingface dataset:
Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans

The efficacy and safety of biological molecules in cancer therapy, such as peptides and small interfering RNAs (siRNAs), could be markedly increased if high concentrations could be achieved and amplified selectively in tumour tissues versus normal tissues after intravenous administration. This has not been achievable so far in humans. We hypothesized that a poxvirus, which evolved for blood-borne systemic spread in mammals, could be engineered for cancer-selective replication and used as a vehicle for the intravenous delivery and expression of transgenes in tumours. JX-594 is an oncolytic poxvirus engineered for replication, transgene expression and amplification in cancer cells harbouring activation of the epidermal growth factor receptor (EGFR)/Ras pathway, followed by cell lysis and anticancer immunity. Here we show in a clinical trial that JX-594 selectively infects, replicates and expresses transgene products in cancer tissue after intravenous infusion, in a dose-related fashion. Normal tissues were not affected clinically. This platform technology opens up the possibility of multifunctional products that selectively express high concentrations of several complementary therapeutic and imaging molecules in metastatic solid tumours in humans.
The DATAS rationale and design: a controlled, randomized trial to assess the clinical benefit of dual chamber (DDED) defibrillator.

Single chamber (SC) implantable cardioverter defibrillators (ICDs) have several limitations that might be relevant during follow-up, like atrial pacing requirements, inadequate therapies, sustained atrial tachyarrhythmias and difficulties to achieve an accurate diagnosis of the arrhythmia. Dual chamber (DC) ICDs offer an attractive and rational solution, although controversy remains if the costs and complexity of these devices offer a real clinical advantage. The Dual Chamber & Atrial Tachyarrhythmias Adverse Events Study (DATAS) was designed to analyze the ability of DC ICD, DDED, to reduce clinically significant adverse events compared with SC ICD in a non-selected population with conventional indications for ICD implantation. This is a prospective, multicentre, randomized, open labelled study, with three arms: two of them (simulated SC ICD and true DC ICD) cross-over, and the third (true SC ICD) parallels the other two. The composite primary end point comprises four Clinically Significant Adverse Events (CSAE): (1) all-cause mortality, (2) invasive intervention, hospitalization or prolongation of hospitalization due to cardiovascular cause, (3) inappropriate shocks, and (4) sustained symptomatic atrial tachyarrhythmias that (a) require urgent termination or (b) last more than 48h leading to therapeutic intervention. Secondary end points constitute each of the individual components of CSAE, cardiovascular status, quality of life and a detailed analysis of atrial and ventricular arrhythmias. To date (June 2003) there have been 343 patients enroled from 947 screened patients. The projected enrollment includes 360 patients and the conclusion of the study is expected at the beginning of 2005.
Oral cisapride for the control of delayed vomiting following high-dose cisplatin

Although combination antiemetics prevent vomiting during the initial 24 h after high-dose (≥100 mg/m2) cisplatin, many patients experience delayed emesis 24–120 h afterwards despite receiving prophylactic dexamethasone and metoclopramide during this time. Cisapride is a prokinetic agent, which stimulates propulsive motility throughout the gastrointestinal tract without causing extrapyramidal effects. In this phase II trial, we tested the ability of cisapride to prevent delayed emesis following cisplatin. Twenty patients receiving initial cisplatin ≥100 mg/m2 were entered. All patients received intravenous dexamethasone with either metoclopramide or ondansetron to prevent acute emesis 0–24 h after receiving cisplatin. Patients who had experienced two or fewer acute vomiting episodes then received cisapride 20 mg orally four times daily for 4 days (24–120 h after cisplatin). Cisapride prevented delayed emesis in 2 patients (10%) during the entire 4-day period (95% confidence interval, 1–32%). Abdominal cramping and pain occurred in 35%. At the dose and schedule tested, oral cisapride prevented delayed emesis in only 10% of patients receiving cisplatin ≥100 mg/m2 and caused abdominal cramping in 35%. Since in prior trials among similar patients, placebo prevented delayed emesis in 11%, further study of cisapride and dose escalation for this indication are not recommended.
The impact of the nocturnal disabilities of Parkinson’s disease on caregivers’ burden: implications for interventions

Parkinson’s disease (PD) imposes a burden on those who care for the person afflicted. The objective of this study was to assess and analyze the main determinants of caregivers’ burden, especially the nocturnal manifestations of PD. This multi-center, national, cross-sectional study included 89 patient–caregiver pairs. Caregiver self-assessments were performed with Hospital Anxiety and Depression Scale (HADS) and Zarit Caregiver Burden Interview (ZCBI). Patient self-assessments were performed with Modified Parkinson’s Disease Sleep Scale (MPDSS), Nocturnal Akinesia Dystonia and Cramp Score (NADCS), HADS and Parkinson’s Disease Quality of Life Questionnaire (PDQ-8). Most of the caregivers were employed women, and the majority had been permanently taking care of the patient for 6.8 ± 5.4 years. The study found that the ZCBI mean score of the caregivers significantly worsened as patients became more dependent (HY: 4–5, p = 0.036), and the mean ZCBI score of spousal caregivers (19.4; SD 15.5) was significantly higher than that of the offspring group (11.7; SD 7.9) (p = 0.008). Disease duration (r = 0.22), NADCS (r = 0.38), MPDSS (r = −0.36), PDQ-8 SI (r = 0.39) and HADS (total, anxiety and depression) scores (r = 0.46–0.49), and HADS (total, anxiety and depression scores (r = 0.37–0.52), had significant negative effect on caregivers’ burden. Moderate association was found on MPDSS item 14 (r = 0.38) and NADCS akinesia score (r = 0.37). Patients’ anxiety, nocturnal akinesia and the feeling of tiredness and sleepiness upon awakening in the morning were independent predictors of caregivers’ burden (adjusted R 2 = 0.46). Based on these findings, treatment of early mood symptoms of the patients and caregivers at risk may be helpful for the effective management of PD and it is also important to have well-designed psycho-educational and multicomponent interventions in the community for caregivers of persons with PD.
Transition of intestinal fatty acid-binding protein on hypothermic circulatory arrest with cardiopulmonary bypass.

Intestinal fatty acid-binding protein (I-FABP) is increasingly employed as a highly specific marker of intestinal necrosis. However, the value of this marker associated with cardiovascular surgery with hypothermic circulatory arrest is unclear. The aim of this study was to measure serum I-FABP levels and provide the transition of I-FABP levels with hypothermic circulatory arrest to help in the management of intestinal perfusion.



From August 2011 to September 2013, 33 consecutive patients who had aortic arch surgery with hypothermic circulatory arrest or heart valve surgery performed were enrolled in the study. Twenty patients had aortic surgery with hypothermic (23-29°C) circulatory arrest and 13 patients had heart valve surgery with cardiopulmonary bypass (33°C).



I-FABP levels increased, both in patients undergoing aortic surgery with hypothermic circulatory arrest and heart valve surgery with cardiopulmonary bypass, reaching peak levels shortly after the administration of protamine. I-FABP levels in patients with aortic surgery were significantly higher with circulatory arrest. They reached peak levels immediately after recirculation and there was a significant drop at the end of surgery (p<0.001). I-FABP levels in heart valve surgery were gradually increased, with the highest at the administration of protamine; they gradually decreased. Peak I-FABP levels were significantly higher in patients undergoing aortic surgery with hypothermic circulatory arrest than in patients with heart valve surgery. However, no postoperative reperfusion injury occurred in the intestinal tract due to the use of hypothermic organ protection.



Plasma I-FABP monitoring could be a valuable method for finding an intestinal ischemia in patients with cardiovascular surgery.
Algorithm 910: A Portable C++ Multiple-Precision System for Special-Function Calculations

This article presents a portable C++ system for multiple precision calculations of special functions called e_float. It has an extendable architecture with a uniform C++ layer which can be used with any suitably prepared MP type. The system implements many high-precision special functions and extends some of these to very large parameter ranges. It supports calculations with 30 ⋯ 300 decimal digits of precision. Interoperabilities with Microsoft’s® CLR, Python, and Mathematica® are supported. The e_float system and its usage are described in detail. Implementation notes, testing results, and performance measurements are provided.
Efficacy and safety of golimumab as add-on therapy to disease-modifying antirheumatic drugs in rheumatoid arthritis: results of the GO-MORE study in Spain.

To assess the efficacy and safety of golimumab in the 140 patients included in Spain as the first part of the GO-MORE trial, a multinational study involving patients with active rheumatoid arthritis (RA) despite treatment with different disease-modifying antirheumatic drugs (DMARDs).



The patients received subcutaneous golimumab 50mg once a month during 6 months. The primary endpoint was the percentage of individuals with a good or moderate EULAR DAS28-ESR response after 6 months of treatment.



A total of 140 patients were included. Of these, 76.4% had very active disease (DAS28-ESR>5.1). 76.4% were taking methotrexate, 40.0% other DMARDs in monotherapy or combined, and 65.0% received corticosteroids. After 6 months, 82.9% of the patients showed a good or moderate EULAR response, 41.4% had low disease activity, and 30.7% were in remission. The percentage of responders one month after the first dose was 69.3%. The efficacy was similar in patients treated with methotrexate or other DMARDs, with different methotrexate doses, with or without corticosteroids, or in subjects who had failed one or more DMARDs. The response to golimumab was observed from the first dose. Golimumab was well tolerated and its safety profile was consistent with the findings of previous studies. Serious adverse events were reported in 11 patients (7.9%).



The addition of subcutaneous golimumab 50 mg once a month to different DMARDs in patients with active RA yielded a moderate or good response after 6 months in 82.9% of the cases. The response was observed early, from the start of the second month, after a single dose of golimumab.
Analysis of Lrrk2 R1628P as a risk factor for Parkinson's disease.

Common genetic variants that increase the risk for Parkinson's disease may differentiate patient subgroups and influence future individualized therapeutic strategies. Herein we show evidence for leucine-rich repeat kinase 2 (LRRK2) c.4883G>C (R1628P) as a risk factor in ethnic Chinese populations. A study of 1,986 individuals from 3 independent centers in Taiwan and Singapore demonstrates that Lrrk2 R1628P increases risk for Parkinson's disease (odds ratio, 1.84; 95% confidence interval, 1.20-2.83; p = 0.006). Haplotype analysis suggests an ancestral founder for carriers approximately 2,500 years ago. These findings support the importance of LRRK2 variants in sporadic Parkinson's disease.
A randomised controlled trial of a self-management education program for osteoarthritis of the knee delivered by health care professionals

Our aim in the present study was to determine whether a disease-specific self-management program for primary care patients with osteoarthritis (OA) of the knee (the Osteoarthritis of the Knee Self-Management Program (OAK)) implemented by health care professionals would achieve and maintain clinically meaningful improvements in health-related outcomes compared with a control group.



Medical practitioners referred 146 primary care patients with OA of the knee. Volunteers with coexistent inflammatory joint disease or serious comorbidities were excluded. Randomisation was to either a control group or the OAK group. The OAK group completed a 6-week self-management program. The control group had a 6-month waiting period before entering the OAK program. Assessments were taken at baseline, 8 weeks and 6 months. The primary outcomes were the results measured using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain and Function subscales on the Short Form 36 version 1 questionnaire (SF-36) Secondary outcomes were Visual Analogue Scale (VAS) pain, Timed Up & Go Test (TUG), knee range of motion and quadriceps and hamstring strength-isometric contraction. Responses to treatment (responders) and minimal clinically important improvements (MCIIs) were determined.



In the OAK group, VAS pain improved from baseline to week 8 from mean (SEM) 5.21 (0.30) to 3.65 (0.29) (P ≤ 0.001). During this period, improvements in the OAK group compared with the control group and responses to treatment were demonstrated according to the following outcomes: WOMAC Pain, Physical Function and Total dimensions, as well as SF-36 Physical Function, Role Physical, Body Pain, Vitality and Social Functioning domains. In addition, from baseline to week 8, the proportion of MCIIs was greater among the OAK group than the control group for all outcomes. For the period between baseline and month 6, WOMAC Pain, Physical Function and Total dimensions significantly improved in the OAK group compared to the control group, as did the SF-36 Physical Function, Role Physical, Body Pain, Vitality and Social Functioning domains, as well as hamstring strength in both legs. During the same period, the TUG Test, range of motion extension and left-knee flexion improved compared with the control group, although these improvements had little clinical relevance.



We recorded statistically significant improvements compared with a control group with regard to pain, quality of life and function for participants in the OAK program on the basis of WOMAC and SF-36 measures taken 8 weeks and 6 months from baseline.
Incidence, correlates, and outcomes of acute, hospital-acquired anemia in patients with acute myocardial infarction.

Anemia is common among patients hospitalized with acute myocardial infarction and is associated with poor outcomes. Less is known about the incidence, correlates, and prognostic implications of acute, hospital-acquired anemia (HAA).



We identified 2909 patients with acute myocardial infarction who had normal hemoglobin (Hgb) on admission in the multicenter TRIUMPH registry and defined HAA by criteria proposed by Beutler and Waalen. We used hierarchical Poisson regression to identify independent correlates of HAA and multivariable proportional hazards regression to identify the association of HAA with mortality and health status. At discharge, 1321 (45.4%) patients had HAA, of whom 348 (26.3%) developed moderate-severe HAA (Hgb <11 g/dL). The incidence of HAA varied significantly across hospitals (range, 33% to 69%; median rate ratio for HAA, 1.13; 95% confidence interval, 1.07 to 1.23, adjusting for patient characteristics). Although documented bleeding was more frequent with more severe HAA, fewer than half of the patients with moderate-severe HAA had any documented bleeding. Independent correlates of HAA included age, female sex, white race, chronic kidney disease, ST-segment elevation myocardial infarction, acute renal failure, use of glycoprotein IIb/IIIa inhibitors, in-hospital complications (cardiogenic shock, bleeding and bleeding severity), and length of stay. After adjustment for GRACE score and bleeding, patients with moderate-severe HAA had higher mortality rates (hazard ratio, 1.82; 95% confidence interval, 1.11 to 2.98 versus no HAA) and poorer health status at 1 year.



HAA develops in nearly half of acute myocardial infarction hospitalizations among patients treated medically or with percutaneous coronary intervention, commonly in the absence of documented bleeding, and is associated with worse mortality and health status. Better understanding of how HAA can be prevented and whether its prevention can improve patient outcomes is needed.
Safety and efficacy of peripheral nerve stimulation of the occipital nerves for the management of chronic migraine: results from a randomized, multicenter, double-blinded, controlled study.

Chronic migraine (CM) is a debilitating neurological disorder with few treatment options. Peripheral nerve stimulation (PNS) of the occipital nerves is a potentially promising therapy for CM patients.



In this randomized, controlled multicenter study, patients diagnosed with CM were implanted with a neurostimulation device near the occipital nerves and randomized 2:1 to active (n = 105) or sham (n = 52) stimulation. The primary endpoint was a difference in the percentage of responders (defined as patients that achieved a ≥50% reduction in mean daily visual analog scale scores) in each group at 12 weeks.



There was not a significant difference in the percentage of responders in the Active compared with the Control group (95% lower confidence bound (LCB) of -0.06; p = 0.55). However, there was a significant difference in the percentage of patients that achieved a 30% reduction (p = 0.01). Importantly, compared with sham-treated patients, there were also significant differences in reduction of number of headache days (Active Group = 6.1, baseline = 22.4; Control Group = 3.0, baseline = 20.1; p = 0.008), migraine-related disability (p = 0.001) and direct reports of pain relief (p = 0.001). The most common adverse event was persistent implant site pain.



Although this study failed to meet its primary endpoint, this is the first large-scale study of PNS of the occipital nerves in CM patients that showed significant reductions in pain, headache days, and migraine-related disability. Additional controlled studies using endpoints that have recently been identified and accepted as clinically meaningful are warranted in this highly disabled patient population with a large unmet medical need.
RCT of timolol maleate gel for superficial infantile hemangiomas in 5- to 24-week-olds.

Timolol maleate 0.5% gel is a safe and effective medication for treating superficial infantile hemangiomas (IHs) in infants with a median age of 9 weeks.



Forty-one infants who had superficial IHs without ulceration and not near mucosal surfaces were recruited and randomly assigned to placebo and treatment (timolol maleate 0.5% gel) groups. Efficacy was assessed by performing blinded volume measurements at weeks 0, 1, 2, 3, 4, 8, 12, 16, 20, and 24 and blinded investigator photograph scoring at weeks 0, 12, and 24. Safety was assessed by measuring heart rate and systolic and diastolic blood pressure at weeks 0, 1, 2, 3, 4, 8, 12, 16, 20, and 24.



Fifteen of the 19 infants receiving treatment and 17 of the 22 infants receiving placebo completed the study. Significant color change on the blinded photographic scores was noted at week 24 of the study (P = .003). There was a significantly higher proportion of treated IHs that reduced in size by >5% at weeks 20 and 24 (P < .02). The predicted proportion of IH volume change was also significantly less for treated IHs from week 16 onward when compared with placebo (P < .05). There was no significant variation in blood pressure and heart rate between the groups.



Topical timolol maleate 0.5% gel with a maximum dose of 0.5 mg per day is a safe and effective option for small superficial IHs that have not ulcerated and are not on mucosal surfaces.
Lack of effect of celecoxib on prostaglandin E2 concentrations in nipple aspirate fluid from women at increased risk of breast cancer.

Cyclooxygenase enzymes (COX-1, COX-2, and COX-3) convert arachidonic acid to prostaglandins, prostacyclins, thromboxanes, and other hydroxy fatty acids. Among these, prostaglandin E(2) (PGE(2)) has tumor growth-promoting activity. The COX-2 isoform is the primary enzyme involved in PGE(2) production in cancerous tissue.



We administered the COX-2 inhibitor celecoxib (200 mg b.i.d.) to women at increased breast cancer risk. Our hypothesis was that PGE(2) would be secreted in breast nipple aspirate fluid (NAF), that levels in NAF would be higher than in corresponding plasma, and that celecoxib would decrease PGE(2) levels in NAF (reflecting a decreased breast tissue eicosanoid production) and plasma.



To determine if PGE(2) concentrations in NAF and plasma decrease after a 2-week course of celecoxib and then return to baseline 2 weeks after stopping the medication (washout).



NAF and plasma were collected before celecoxib treatment, 2 weeks after taking celecoxib, and 2 weeks after washout. Each woman served as her own control.



PGE(2) concentrations in NAF and plasma were detectable in samples using two measurement techniques. On average, NAF PGE(2) levels were 81-fold higher in NAF than in matched plasma. Technically, there were differences in PGE(2) concentrations measured in similar fluids depending on the assay technique used (RIA versus chemiluminescence immunoassay). There were no significant decreases in PGE(2) concentrations after celecoxib administration.



PGE(2) can be measured in NAF. PGE(2) levels are concentrated in NAF when compared with matched plasma samples. Celecoxib 200 mg b.i.d. does not appear to significantly decrease PGE(2) concentrations in NAF and plasma.
A Finite Element Study of the Dynamic Response of Brain Based on Two Parasagittal Slice Models

The objective of this study is to investigate the influence of gyri and sulci on the response of human head under transient loading. To this end, two detailed parasagittal slice models with and without gyri and sulci have been developed. The models comprised not only cerebrum and skull but also cerebellum, brain stem, CSF, and corpus callosum. In addition, white and gray matters were separated. The material properties were adopted from the literature and assigned to different parts of the models. Nahum's and Trosseille's experiments reported in relevant literature were simulated and the simulation results were compared with the test data. The results show that there is no evident difference in terms of intracranial pressure between the models with and without gyri and sulci under simulated conditions. The equivalent stress below gyri and sulci in the model with gyri and sulci is slightly higher than that in the counterpart model without gyri and sulci. The maximum principle strain in brain tissue is lower in the model with gyri and sulci. The stress and strain distributions are changed due to the existence of gyri and sulci. These findings highlight the necessity to include gyri and sulci in the finite element head modeling.