nils-herrmann/clean_scirepeval huggingface dataset:
Multiple sclerosis as a cause of the acute vestibular syndrome

Multiple sclerosis (MS) causes dizziness and vertigo. Reports suggest responsible lesions are often in the intra-pontine 8th nerve fascicle. We sought to determine frequency and clinical features of demyelinating acute vestibular syndrome (AVS). This is a prospective observational study (1999–2011). Consecutive AVS patients (vertigo, nystagmus, nausea/vomiting, head-motion intolerance, unsteady gait) with a risk for central localization underwent structured bedside examination and neuroimaging. When applicable, we identified MS based on clinical, imaging, and laboratory features. Of 170 AVS presentations, 4 % (n = 7) were due to demyelinating disease. Five had an acute MS plaque likely responsible for the clinical syndrome. Lesion location varied—1 medulla; 1 inferior cerebellar peduncle; 1 middle cerebellar peduncle; 1 posterior pontine tegmentum; 1 in the intrapontine 8th nerve fascicle; 1 superior cerebellar peduncle; 1 midbrain. Only two had a lesion in or near the intra-pontine 8th nerve fascicle. Three were first presentations (i.e., clinically isolated demyelinating syndrome), while the others were known MS. All had central oculomotor signs. In two patients, the only central sign was a normal horizontal head impulse test (h-HIT) of vestibular function. All patients improved with steroid therapy. Demyelinating disease was an uncommon cause of AVS in our series. Symptomatic lesions were not restricted to the 8th nerve fascicle. Five patients had relatively obvious oculomotor signs, making differentiation from vestibular neuritis straightforward. Two patients had unidirectional, horizontal nystagmus that followed Alexander’s law and was suppressed with fixation (true pseudoneuritis). The presence of a normal h-HIT in these suggested central localization.
Value of self-performed joint counts in rheumatoid arthritis patients near remission

To determine the validity and reliability of patients' self-performed joint counts compared to joint counts by professional assessors in rheumatoid arthritis (RA) patients in different disease activity states.



In patients with established RA we determined the inter-rater reliability of joint counts performed by an independent evaluator and the patient using intraclass correlation (ICC), and agreement on activity in individual joints by kappa statistics. We also performed longitudinal analyses to assess consistency of assessments over time. Finally, we investigated the concordance of joint counts of different assessors in patients with different levels of disease activity.



The reliability of patient self-performed joint counts was high when compared to independent objective assessment (ICC; 95%confidence interval (CI)) for the assessment of swelling (0.32; 0.15 to 0.46) and tenderness (0.75; 0.66 to 0.81), with higher agreement for larger joints (kappa: 0.57 and 0.45, respectively) compared to smaller joints (metacarpo-phalangeal joint (MCPs): 0.31 and 0.45; and proximal interphalangeal joint (PIPs): 0.22 and 0.47, for swelling and tenderness, respectively).Patients in remission according to the Simplified Disease Activity Index (SDAI ≤ 3.3) showed better concordance of the joint counts (swollen joint count (SJC) ties 25/37, tender joint count (TJC) ties 26/37) compared to moderate/high disease activity states (SDAI > 11; MDA/HDA: SJC ties 9/72, TJC ties 21/72). Positive and negative predictive values regarding the presence of SDAI remission were reasonably good (0.86 and 0.95, respectively). A separate training session for patients did not improve the reliability of joint assessment. The results were consistent in the longitudinal analyses.



Self-performed joint counts are particularly useful for monitoring in patients having attained remission, as these patients seem able to detect state of remission.
Role of cortisol in the pathogenesis of deficient counterregulation after antecedent hypoglycemia in normal humans.

The aim of this study was to determine the role of increased plasma cortisol levels in the pathogenesis of hypoglycemia-associated autonomic failure. Experiments were carried out on 16 lean, healthy, overnight fasted male subjects. One group (n = 8) underwent two separate, 2-d randomized experiments separated by at least 2 mo. On day 1 insulin was infused at a rate of 1.5 mU/kg per min and 2 h clamped hypoglycemia (53 +/- 2 mg/dl) or euglycemia (93 +/- 3 mg/dl) was obtained during morning and afternoon. The next morning subjects underwent a 2-h hyperinsulinemic (1.5 mU/kg per min) hypoglycemic (53 +/- 2 mg/dl) clamp study. In the other group (n = 8), day 1 consisted of morning and afternoon 2-h clamped hyperinsulinemic euglycemia with cortisol infused to stimulate levels of plasma cortisol occurring during clamped hypoglycemia (53 mg/dl). The next morning (day 2) subjects underwent a 2-h hyperinsulinemic hypoglycemic clamp identical to the first group. Despite equivalent day 2 plasma glucose and insulin levels, steady state epinephrine, norepinephrine, pancreatic polypeptide, glucagon, ACTH and muscle sympathetic nerve activity (MSNA) values were significantly (R < 0.01) blunted after day 1 cortisol infusion compared to antecedent euglycemia. Compared to day 1 cortisol, antecedent hypoglycemia produced similar blunted day 2 responses of epinephrine, norepinephrine, pancreatic polypeptide and MSNA compared to day 1 cortisol. Antecedent hypoglycemia, however, produced a more pronounced blunting of plasma glucagon, ACTH, and hepatic glucose production compared to day 1 cortisol. We conclude that in healthy overnight fasted men (a) antecedent physiologic increases of plasma cortisol can significantly blunt epinephrine, norepinephrine, glucagon, and MSNA responses to subsequent hypoglycemia and (b) these data suggest that increased plasma cortisol is the mechanism responsible for antecedent hypoglycemia causing hypoglycemia associated autonomic failure.
Risk factors for mortality during antiretroviral therapy in older populations in resource-limited settings

An increasing proportion of adult patients initiating antiretroviral therapy (ART) in resource-limited settings are aged > 50 years. Older populations on ART appear to have heightened risk of death, but little is known about factors influencing mortality in this population.



We performed a retrospective observational multisite cohort study including all adult patients (≥ 15 years) initiating ART between 2003 and 2013 in programmes supported by Médecins Sans Frontières across 12 countries in Asia, Africa and Europe. Patients were stratified into two age groups, > 50 years and 15 to 50 years. A Cox proportional hazards model was used to explore factors associated with mortality.



The study included 41,088 patients: 2591 (6.3%) were aged > 50 years and 38,497 (93.7%) were aged 15 to 50 years. The mortality rate was significantly higher in the age group > 50 years [367 (14.2%) deaths; mortality rate 7.67 deaths per 100 person-years (95% confidence interval, CI: 6.93 to 8.50)] compared to the age group 15 to 50 years [3788 (9.8%) deaths; mortality rate 4.18 deaths per 100 person-years (95% CI: 4.05 to 4.31)], p < 0.0001. Higher CD4 levels at baseline were associated with significantly reduced mortality rates in the 15 to 50 age group but this association was not seen in the > 50 age group.  Stage 4 conditions were more strongly associated with increased mortality rates in the 15 to 50 age group compared to populations > 50 years.  Stage 3 conditions were associated with an increased mortality rate in the 15 to 50 age group but not in the > 50 age group. Programme region did not affect mortality rates in the > 50 age group; however being in an Asian programme was associated with a 36% reduced mortality rate in populations aged 15 to 50 years compared to being in an African programme. There was a higher overall incidence of Stage 3 WHO conditions in people > 50 years (12.8/100 person-years) compared to those 15 to 50 years (8.1/100 person-years) (p < 0.01). The rate of Stage 4 WHO conditions was similar (5.8/100 versus 6.1/100 respectively, p = 0.52). Mortality rates on ART associated with the majority of specific WHO conditions were similar between the 15 to 50 and > 50 age groups.



Older patients on ART in resource-limited settings have increased mortality rates, but compared to younger populations this appears to be less influenced by baseline CD4 count and WHO clinical stage. HIV treatment programmes in resource-limited settings need to consider risk factors associated with mortality on ART in older populations, which may differ to those related to younger adults.
The time problem

The notion of time in Ada is necessary since the language is intended for use in programming embedded real-time systems. In this chapter, we examine time related issues in Ada and their relation to our approach to benchmarking. There are two aspects of the time problem area that must be considered in performance evaluation. The first is a need for benchmark programs to evaluate the timing related features of the language. Secondly, the existence of timing support provides the basis for developing a method within the language for measuring benchmark execution times. In order to develop an accurate and reliable method for timing measurement, the support for timing provided by the language must be calibrated using benchmark programs. We discuss these two inter-related areas of the time problem in the paragraphs below, after first reviewing the notion of time present in
Allogeneic stem cell transplantation in paroxysmal nocturnal hemoglobinuria.

In the era of eculizumab, identifying patients with paroxysmal nocturnal hemoglobinuria who may benefit from allogeneic stem cell transplantation is challenging.



We describe the characteristics and overall survival of 211 patients transplanted for paroxysmal nocturnal hemoglobinuria in 83 EBMT centers from 1978 to 2007. Next, we conducted a comparison with a cohort of 402 non-transplanted patients with paroxysmal nocturnal hemoglobinuria diagnosed between 1950 and 2005 in 92 French centers. We compared the occurrence of complications (i.e. thromboembolism and aplastic anemia) using either an individual or a stratum-matching procedure.



After a median follow-up of 5 years, the 5-year overall survival rate ± standard error (%) was 68 ± 3 in the transplanted group (54 ± 7 in the case of thromboembolism, 69 ± 5 in the case of aplastic anemia without thromboembolism and 86 ± 6 in the case of recurrent hemolytic anemia without thromboembolism or aplastic anemia). Only thromboembolism as the indication for transplantation was associated with worse outcome (P=0.03). We identified 24 pairs of transplanted and non-transplanted patients with thromboembolism for the matched comparison, with worse overall survival for the transplanted patients (hazard ratio=10.0; 95% confidence interval, 1.3-78.1; P=0.007). This was confirmed by the global matching procedure (P=0.03). As regards aplastic anemia without thromboembolism, 30 pairs were identified for the matched comparison. It was not observed that transplanted patients had a significantly worse overall survival (hazard ratio=4.0; 95% confidence interval, 0.9-18.9; P=0.06). A global matching procedure was not feasible.



Allogeneic stem cell transplantation is probably not a suitable treatment option for life-threatening thromboembolism in paroxysmal nocturnal hemoglobinuria.
Effect of Postextubation High-Flow Nasal Cannula vs Conventional Oxygen Therapy on Reintubation in Low-Risk Patients: A Randomized Clinical Trial.

Studies of mechanically ventilated critically ill patients that combine populations that are at high and low risk for reintubation suggest that conditioned high-flow nasal cannula oxygen therapy after extubation improves oxygenation compared with conventional oxygen therapy. However, conclusive data about reintubation are lacking.



To determine whether high-flow nasal cannula oxygen therapy is superior to conventional oxygen therapy for preventing reintubation in mechanically ventilated patients at low risk for reintubation.



Multicenter randomized clinical trial conducted between September 2012 and October 2014 in 7 intensive care units (ICUs) in Spain. Participants were 527 adult critical patients at low risk for reintubation who fulfilled criteria for planned extubation. Low risk for reintubation was defined as younger than 65 years; Acute Physiology and Chronic Health Evaluation II score less than 12 on day of extubation; body mass index less than 30; adequate secretions management; simple weaning; 0 or 1 comorbidity; and absence of heart failure, moderate-to-severe chronic obstructive pulmonary disease, airway patency problems, and prolonged mechanical ventilation.



Patients were randomized to undergo either high-flow or conventional oxygen therapy for 24 hours after extubation.



The primary outcome was reintubation within 72 hours, compared with the Cochran-Mantel-Haenszel χ2 test. Secondary outcomes included postextubation respiratory failure, respiratory infection, sepsis and multiorgan failure, ICU and hospital length of stay and mortality, adverse events, and time to reintubation.



Of 527 patients (mean age, 51 years [range, 18-64]; 62% men), 264 received high-flow therapy and 263 conventional oxygen therapy. Reintubation within 72 hours was less common in the high-flow group (13 patients [4.9%] vs 32 [12.2%] in the conventional group; absolute difference, 7.2% [95% CI, 2.5% to 12.2%]; P = .004). Postextubation respiratory failure was less common in the high-flow group (22/264 patients [8.3%] vs 38/263 [14.4%] in the conventional group; absolute difference, 6.1% [95% CI, 0.7% to 11.6%]; P = .03). Time to reintubation was not significantly different between groups (19 hours [interquartile range, 12-28] in the high-flow group vs 15 hours [interquartile range, 9-31] in the conventional group; absolute difference, -4 [95% CI, -54 to 46]; P = .66]. No adverse effects were reported.



Among extubated patients at low risk for reintubation, the use of high-flow nasal cannula oxygen compared with conventional oxygen therapy reduced the risk of reintubation within 72 hours.
Feedback-Mediated Upper Extremities Exercise: Increasing Patient Motivation in Poststroke Rehabilitation

This proof-of-concept study investigated whether feedback-mediated exercise (FME) of the affected arm of hemiplegic patients increases patient motivation and promotes greater improvement of motor function, compared to no-feedback exercise (NFE).



We developed a feedback-mediated treatment that uses gaming scenarios and allows online and offline monitoring of both temporal and spatial characteristics of planar movements. Twenty poststroke hemiplegic inpatients, randomly assigned to the FME and NFE group, received therapy five days a week for three weeks. The outcome measures were evaluated from the following: (1) the modified drawing test (mDT), (2) received therapy time-RTT, and (3) intrinsic motivation inventory-IMI.



The FME group patients showed significantly higher improvement in the speed metric (P < 0.01), and smoothness metric (P < 0.01), as well as higher RTT (P < 0.01). Significantly higher patient motivation is observed in the FME group (interest/enjoyment subscale (P < 0.01) and perceived competence subscale (P < 0.01)).



Prolonged endurance in training and greater improvement in certain areas of motor function, as well as very high patient motivation and strong positive impressions about the treatment, suggest the positive effects of feedback-mediated treatment and its high level of acceptance by patients.
Effect of morphine in needle procedures in children with cancer.

The aim was to investigate whether children experience less fear, distress, and/or pain when they receive oral morphine vs. placebo before a needle is inserted in a subcutaneously implanted intravenous port when combined with topical anesthesia.



Fifty children 1-18 years of age who were treated in a pediatric oncology and hematology setting were included consecutively when undergoing routine needle insertion into an intravenous port. All children were subjected to one needle insertion following topical anesthetic (EMLA) application in this randomized, triple-blind, placebo-controlled study comparing orally administered morphine (n=26) 0.25 mg/kg body weight with placebo (n=24). The patients' fear, distress, and pain were reported by parents, nurses and the children themselves (if ≥ 7 years of age) on 0-100 mm Visual Analogue Scales. In addition, observational methods were used to measure distress and procedure pain.



No differences between the morphine and the placebo group were found with respect to age, weight, height, physical status, sex, weeks from diagnosis, or weeks from latest needle insertion. According to, parents, nurses, and children, oral morphine at a dose of 0.25 mg/kg body weight did not reduce fear, distress or pain compared with placebo.



We could not reject the null hypothesis that there is no difference between the oral morphine and placebo groups assuming an effect size of 15 mm on VAS. Therefore it seems that oral morphine at 0.25 mg/kg does not give any additional reduction of fear, distress or pain compared with placebo when combined with topical anesthesia in pediatric patients undergoing subcutaneous port needle insertion, and would not be expected to be of any advantage for similar procedures such as venipuncture and venous cannulation when topical anesthesia is used.
Fructus phyllanthi tannin fraction induces apoptosis and inhibits migration and
invasion of human lung squamous carcinoma cells in vitro via MAPK/MMP
pathways

Fructus phyllanthi tannin fraction (PTF) from the traditional Tibetan medicine Fructus phyllanthi has been found to inhibit lung and liver carcinoma in mice. In this study we investigated the anticancer mechanisms of PTF in human lung squamous carcinoma cells in vitro.Human lung squamous carcinoma cell line (NCI-H1703), human large-cell lung cancer cell line (NCI-H460), human lung adenocarcinoma cell line (A549) and human fibrosarcoma cell line (HT1080) were tested. Cell viability was detected with MTT assay. Cell migration and invasion were assessed using a wound healing assay and a transwell chemotaxis chambers assay, respectively. Cell apoptosis was analyzed with flow cytometric analysis. The levels of apoptosis-related and metastasis-related proteins were detected by Western blot and immunofluorescence.PTF dose-dependently inhibited the viability of the 3 human lung cancer cells. The IC50 values of PTF in inhibition of NCI-H1703, NCI-H460, and A549 cells were 33, 203, and 94 mg/L, respectively. PTF (15, 30, and 60 mg/L) dose-dependently induced apoptosis of NCI-H1703 cells. Treatment of NCI-H1703 and HT1080 cells with PTF significantly inhibited cell migration, and reduced the number of invasive cells through Matrigel. Furthermore, PTF dose-dependently down-regulated the expression of phosphor-ERK1/2, MMP-2 and MMP-9, up-regulated the expression of phosphor-JNK, but had no significant effect on the expression of ERK1/2 or JNK.Conclusion:PTF induces cell apoptosis and inhibits the migration and invasion of NCI-H1703 cells by decreasing MPPs expression through regulation of the MAPK pathway.
Can response-adaptive randomization increase participation in acute stroke trials?

A response-adaptive randomization (RAR) trial design actively adjusts the ratio of participants assigned to each trial arm, favoring the better performing treatment by using outcome data from participants already in the trial. Compared with a standard clinical trial, an RAR study design has the potential to improve patient participation in acute stroke trials.



This cross-sectional randomized survey included adult emergency department patients, age≥18, without symptoms of stroke or other critical illness. A standardized protocol was used, and subjects were randomized to either an RAR or standard hypothetical acute stroke trial. After viewing the video describing the hypothetical trial (http://youtu.be/cKIWduCaPZc), reviewing the consent form, and having questions answered, subjects indicated whether they would consent to the trial. A multivariable logistic regression model was fitted to estimate the impact of RAR while controlling for demographic factors and patient understanding of the design.



A total of 418 subjects (210 standard and 208 RAR) were enrolled. All baseline characteristics were balanced between groups. There was significantly higher participation in the RAR trial (67.3%) versus the standard trial (54.5%), absolute increase: 12.8% (95% confidence interval, 3.7-22.2). The RAR group had a higher odds ratio of agreeing to research (odds ratio, 1.89; 95% confidence interval, 1.2-2.9) while adjusting for patient level factors. Trial designs were generally well understood by the participants.



The hypothetical RAR trial attracted more research participation than standard randomization. RAR has the potential to increase recruitment and offer benefit to future trial participants.
The epiconus syndrome presenting with radicular-type neurological features

We report 15 patients with an epiconus syndrome presenting with radicular-type clinical features involving the lower extremities and identify the vertebral level at which the spinal cord terminated. All patients, consisting of 10 men and five women, aged 37 to 71 years, presented with unilateral or bilateral leg muscle atrophy as well as sensory deficit. Unilateral or bilateral reduction or absence of deep tendon reflexes were present in 13 patients, while pathological reflexes were seen in three cases and bladder dysfunction in 10. Prior to presentation, five patients with the epiconus syndrome were mistakenly diagnosed as having different spinal diseases, which were treated surgically. The level of epiconus compromise detected on radiological examination ranged from the lower level of the T10 vertebra to T12-L1 intervertebral disc level, but most frequently at T11-12 disc level. The level of termination of the spinal cord was between T12 and L1-2 disc level, but most frequently at the middle portion of the L1 vertebra, which was on average 1.6±0.4 (mean±standard deviation) vertebrae distal to the epiconus lesions. The presence of different neurological features related to epiconus compromise should be carefully examined with reference to the level of termination of the spinal cord.