nils-herrmann/clean_scirepeval huggingface dataset:
Inflammatory basis of exercise-induced bronchoconstriction.

Exercise-induced bronchoconstriction (EIB) is a highly prevalent condition with unclear pathogenesis. Two competing theories of the pathogenesis of EIB differ regarding the inflammatory basis of this condition.



Our goals were to establish whether epithelial cell and mast cell activation with release of inflammatory mediators occurs during EIB and how histamine and cysteinyl leukotriene antagonists alter the airway events occurring during EIB.



Induced sputum was used to measure mast cell mediators and eicosanoids at baseline and 30 minutes after exercise challenge in 25 individuals with asthma with EIB. In a randomized, double-blind crossover study, the cysteinyl leukotriene antagonist montelukast and antihistamine loratadine or two matched placebos were administered for two doses before exercise challenge.



The percentage of columnar epithelial cells in induced sputum at baseline was associated with the severity of EIB. After exercise challenge, histamine, tryptase, and cysteinyl leukotrienes significantly increased and prostaglandin E(2) and thromboxane B(2) significantly decreased in the airways, and there was an increase in columnar epithelial cells in the airways. The concentration of columnar epithelial cells was associated with the levels of histamine and cysteinyl leukotrienes in the airways. Treatment with montelukast and loratadine inhibited the release of cysteinyl leukotrienes and histamine into the airways, but did not inhibit the release of columnar epithelial cells into the airways.



These data indicate that epithelial cells, mast cell mediators, and eicosanoids are released into the airways during EIB, supporting an inflammatory basis for EIB.
Feasibility and safety of frequency-domain optical coherence tomography for coronary artery evaluation: a single-center study

We assessed the feasibility and safety of frequency-domain optical coherence tomography (FD–OCT) in a variety of indications. We conducted a retrospective analysis of all FD–OCT examinations performed for research and clinical indications, including stable angina, acute coronary syndromes, diagnostic procedures and percutaneous coronary intervention (PCI), at the Satakunta Central Hospital (Pori, Finland) between August 12th 2009 and February 9th 2011. All pullbacks were screened for image quality. Data on complications and clinical implications of examinations was obtained from patient records. The mean age of the patients was 65.9 ± 10.9 years (81.7 % males). A total of 230 examinations were performed on 210 patients; 523 pullbacks were eventually attempted (519 successful). On average, 2.3 ± 1.1 pullbacks were performed, and 1.1 ± 0.4 vessels were scanned per examination. PCI was performed in 44.3 % of examinations. Radial access was used in 70.3 % of cases. Examination was successful in 202 (87.8 %) examinations. One patient died of heart failure later after PCI for acute myocardial infarction. No cases of major bleeding, myocardial infarction, contrast-induced nephropathy, or pericardial tamponade were encountered. Chest pain occurred in 10.9 % of examinations, minor bleeding in 4.8 %, and myocardial ischemia in 2.6 %. Femoral access was associated with fewer blood and decentration artefacts and a trend towards better image quality when compared to radial access, with no difference in complications. After the first 50 examinations, there appeared to be fewer artefacts in the subsequent examinations. The current study demonstrated that FD–OCT is feasible, with infrequent complications.
BrickRoad: a light-weight tool for spontaneous design of location-enhanced applications

It is difficult to design and test location-enhancedapplications. A large part of this difficulty is due to the added complexity of supporting location. Wizard of Oz (WOz) has become an effective technique for the early stage design of location-enhanced applications because it allows designers to test an application prototype bysimulating nonexistent components such as location sensing. However, existing WOz tools 1) require nontrivial effort from designers to specify how a prototype should behave before it can be tested with end users, and 2)support only limited control over application behavior during a test. BrickRoad is a WOz tool for spontaneousdesign of location-enhanced applications. It lowers the threshold to acquiring user feedback and exploring a design space. With BrickRoad, a designer does not need to specify any interaction logic and can experiment on-the-fly with different designs during testing. BrickRoad is a valuable complement to existing tool support for the early stage design of location-enhanced applications.
Decrease of the atrial fibrillatory rate, increased organization of the atrial rhythm and termination of atrial fibrillation by AZD7009.

The atrial fibrillatory rate (AFR), on AZD7009 as compared to placebo, was investigated as a potential biomarker for electrophysiological effect in early antiarrhythmic drug development.



Patients with permanent AF received infusions of AZD7009 and placebo in an exploratory two-way, single-blind, randomized cross-over study. The ECG was continuously recorded, and following QRST cancellation the AFR, its standard deviation (SD), the exponential decay and the atrial electrogram amplitude were determined as 3-min averages.



The mean AFR rapidly decreased by 43% from baseline (394 ± 38 to 225 ± 61 fibrillations/min, p=0.0003) on AZD7009, but not on placebo. The SD of the AFR and the exponential decay decreased in parallel. In 2 of 8 patients, termination of AF occurred after the AFR had decreased by 58% and 53%, respectively.



The AFR may potentially serve as a biomarker of electrophysiological effects in early evaluation of rhythm control agents.
Association of the preoperative neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios with lymph node metastasis and recurrence in patients with medullary thyroid carcinoma

The preoperative neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are known to be prognostic factors in several cancers. However, no previous investigation has been performed to evaluate the significance of the NLR and PLR in medullary thyroid carcinoma (MTC).The aim of this study was to identify the ability of the preoperative NLR or PLR to predict lymph node metastasis and recurrence in patients with MTC. Data from all patients with MTC who had undergone surgery at our institution from May 2009 to May 2016 were retrospectively evaluated. Receiver operating characteristic (ROC) analysis was performed to identify optimal NLR and PLR cutoff points, and we assessed independent predictors of lymph node metastasis and recurrence using univariate and multivariate analyses.Based on the inclusion and exclusion criteria, a total of 70 patients were enrolled in this study. The ideal cutoff points for predicting lymph node involvement were 2.7 for the NLR and 105.3 for the PLR. The optimal cutoff points of the NLR and PLR for predicting recurrence were 2.8 and 129.8, respectively. Using the cutoff values, we found that PLR>105.3 (odds ratio [OR] 4.782, 95% confidence interval [CI] 1.4-16.7) was an independent predictor of lymph node metastasis and that PLR>129.8 (OR 3.838, 95% CI 1.1-13.5) was an independent predictor of recurrence.Our study suggests that the preoperative PLR, but not NLR, was significantly associated with lymph node metastasis and recurrence in patients with MTC.
The illness perceptions associated with health and behavioural outcomes in people with musculoskeletal hand problems: findings from the North Staffordshire Osteoarthritis Project (NorStOP).

Illness perceptions may influence health outcomes, including pain. The objective of the study was to investigate the illness perceptions associated with health and behaviour in a population of older adults with musculoskeletal hand problems.



A two-stage cross-sectional postal survey was sent to individuals aged 50 yrs and over, registered with three general practices in North Staffordshire. Stage 1, a Health Survey questionnaire, was sent to 11,230 individuals and enquired about general health status, including anxiety and depression. Individuals reporting hand problems at Stage 1 were sent Stage 2, a detailed hand questionnaire. The hand questionnaire included: the Arthritis Impact Measurement Scales 2 (AIMS2) (hand and finger function, pain and medication scales), and questions on self-reported diagnoses and general practitioner (GP) consultation. Perceptions were measured by the Illness Perceptions Questionnaire-Revised (IPQ-R), and an item on perceived frustration with their hand problems. Of the 7878 responders to the Health Survey questionnaire 3749 (47.6%) reported 'hand problems' and 2695 (71.9%) gave permission to be re-contacted. The hand questionnaire was completed by 2113 (adjusted response rate 78.6%).



A belief that their hand problem had a profound impact on life, caused a range of symptoms and made them frustrated were the perceptions most strongly and consistently associated with health and behaviour. There was little difference between individuals who did and those who did not report their hand problem to be osteoarthritis with respect to perceptions or between perceptions associated with health and behaviour.



The results suggest that older people who consider their musculoskeletal hand problem to have negative effects on their life will be more likely to encounter difficulties that may lead them to consult, take medication or both. Understanding the illness perceptions of these individuals may identify opportunities for intervention.
Antenatal magnesium sulfate exposure and acute cardiorespiratory events in preterm infants.

Antenatal magnesium (anteMg) is used for various obstetric indications including fetal neuroprotection. Infants exposed to anteMg may be at risk for respiratory depression and delivery room (DR) resuscitation. The study objective was to compare the risk of acute cardiorespiratory events among preterm infants who were and were not exposed to anteMg.



This was a retrospective analysis of prospective data collected in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network's Generic Database from April 1, 2011, through March 31, 2012. The primary outcome was DR intubation or respiratory support at birth or on day 1 of life. Secondary outcomes were invasive mechanical ventilation, hypotension treatment, neonatal morbidities, and mortality. Logistic regression analysis evaluated the risk of primary outcome after adjustment for covariates.



We evaluated 1544 infants <29 weeks' gestational age (1091 in anteMg group and 453 in nonexposed group). Mothers in the anteMg group were more likely to have higher education, pregnancy-induced hypertension, and antenatal corticosteroids, while their infants were younger in gestation and weighed less (P < .05). The primary outcome (odds ratio [OR], 1.2; 95% confidence interval [CI], 0.88-1.65) was similar between groups. Hypotension treatment (OR, 0.70; 95% CI, 0.51-0.97) and invasive mechanical ventilation (OR, 0.54; 95% CI, 0.41-0.72) were significantly less in the anteMg group.



Among preterm infants age <29 weeks' gestation, anteMg exposure was not associated with an increase in cardiorespiratory events in the early newborn period. The safety of anteMg as measured by the need for DR intubation or respiratory support on day 1 of life was comparable between groups.
Influence of aminoglutethimide on plasma oestrogen levels in breast cancer patients on 4-hydroxyandrostenedione treatment

The clinical and biochemical effects of combined treatment with the two aromatase inhibitors aminoglutethimide and 4-hydroxyandrostenedione were evaluated in 10 patients suffering from advanced breast cancer. All patients had become resistant to treatment with one of the drugs before having combined treatment. Seven patients progressing on 4-hydroxyandrostenedione who had aminoglutethimide added to their treatment and achieved a further suppression of plasma oestradiol by a mean of 40.0% (p<0.05). Plasma oestrone was suppressed by a mean of 40.6% (p<0.025) and plasma oestrone sulphate was suppressed by a mean of 63.6% (p<0.025). Two of the patients, neither of whom had responded to 4-hydroxyandrostenedione alone, experienced objective tumour regression when aminoglutethimide was given in concert. Three patients progressing on aminoglutethimide who had 4-hydroxyandrostenedione added showed no further suppression of their plasma oestrogen levels, and no tumour regression was observed. These findings suggest a dose-response relationship between plasma oestrogen suppression at low postmenopausal levels and objective tumour response in breast cancer.
Hysteroscopic Resection in Fertility-Sparing Surgery for Atypical Hyperplasia and Endometrial Cancer: Safety and Efficacy.

To evaluate the rate of intrauterine adhesions after hysteroscopic resection of hyperplastic and/or cancer areas and the efficacy of combined treatment.



Observational retrospective study.



Patients affected by endometrial atypical hyperplasia of the endometrium or early stage endometrial carcinoma.



Twenty-three patients, up to 45 years of age.



Conservative treatment based on hysteroscopic resection of hyperplastic and/or cancer areas and subsequent therapy with megestrol acetate 160 mg/day.



Approximately 5% of endometrial cancers (ECs) are diagnosed in women younger than 40 years old, usually with a good prognosis. From 2010 to 2014, 23 patients, up to age 45 years, who were affected by endometrial cancer (EC) grade 1 or atypical complex hyperplasia (ACH) and who wished to preserve fertility, underwent conservative treatment based on hysteroscopic resection of the hyperplastic and/or cancer areas and subsequent therapy with megestrol acetate 160 mg/day. Data with regard to age, body mass index, symptoms, history of infertility, and previous assisted reproductive technologies attempts, obstetrics history, previous diagnosis of intrauterine sinechiae, hysteroscopic findings, duration of therapy, follow-up reports, and reproductive outcomes were collected and analyzed. Of the 23 patients enrolled in the study, 3 patients (13%) presented with an endometrioid EC grade 1, and 20 patients (87%) had ACH. Twelve patients (52.2%) had complete remission after 3 months of progestin therapy, 9 patients (39.1%) had a complete remission after 6 months, and 2 (8.7%) patients had remission after 9 months. Six patients underwent a second hysteroscopic resection. The 3 patients with an initial diagnosis of EC had complete remission after a mean of 4 months of high-dose progestin therapy; in patients with ACH, remission occurred after a mean of 3 months. In all patients, intrauterine adhesions were not detected at any follow-up diagnostic hysteroscopy. After a median follow-up time of 25 months (range 8-37), we registered 1 (4.3%) relapse of disease. A total of 7 pregnancies in 6 patients were counted, after an average time of 7.4 months (range 3-13 months) after the end of progestin therapy.



Hysteroscopic resection of hyperplastic and/or cancer areas before high dosage progestin therapy seems to be a safe and effective approach in the management of ACH and in patients with early EC who wish to preserve fertility.
Using videotelephony to support paediatric oncology-related palliative care in the home: from abandoned RCT to acceptability study.

Videotelephony (real-time audio-visual communication) has been used successfully in adult palliative home care. This paper describes two attempts to complete an RCT (both of which were abandoned following difficulties with family recruitment), designed to investigate the use of videotelephony with families receiving palliative care from a tertiary paediatric oncology service in Brisbane, Australia. To investigate whether providing videotelephone-based support was acceptable to these families, a 12-month non-randomised acceptability trial was completed. Seventeen palliative care families were offered access to a videotelephone support service in addition to the 24 hours 'on-call' service already offered. A 92% participation rate in this study provided some reassurance that the use of videotelephones themselves was not a factor in poor RCT participation rates. The next phase of research is to investigate the integration of videotelephone-based support from the time of diagnosis, through outpatient care and support, and for palliative care rather than for palliative care in isolation.
Aspirin Reduces Plasma Concentrations of the Oncometabolite 2-Hydroxyglutarate: Results of a Randomized, Double-Blind, Crossover Trial.

Aspirin use is an effective strategy for the chemoprevention of colorectal cancer, even at low doses. However, in order to implement aspirin interventions, risk-benefit balances and biologic mechanisms need to be better defined; to further this aim, we used a metabolomics approach.



We metabolically profiled 40 healthy, nonsmoking men and women ages 20 to 45 years enrolled in a randomized, double-blind, crossover trial of 325 mg aspirin/day over a period of 60 days. Gas and liquid chromatography-mass spectrometry were used to comprehensively profile participants' plasma samples after aspirin and placebo interventions.



A total of 363 metabolites, covering most human biochemical pathways, were measured. Compared with placebo-treated participants, plasma concentrations of the oncometabolite 2-hydroxyglutarate (R+S) decreased after aspirin treatment in both men and women (P = 0.005). This signal proved robust during 20-fold random splitting of the data using 80% of the samples in each split. We subsequently performed functional follow-up studies using targeted, enantiospecific detection in human colorectal cancer cell lines and observed an aspirin-induced reduction of (R)-2-hydroxyglutarate. We further showed that salicylate, the primary aspirin metabolite, inhibits the hydroxyacid-oxoacid transhydrogenase mediated production of (R)-2-hydroxyglutarate, thereby providing mechanistic evidence for the clinically observed effects of aspirin on total-2-hydroxyglutarate.



Using a metabolomics approach with functional follow-up, we propose that a decrease in the oncometabolite (R)-2-hydroxyglutarate may identify an additional mechanism for aspirin or its metabolites in cancer prevention.



Reduction of the oncometabolite (R)-2-hydroxyglutarate identifies a novel, non-COX-inhibition-mediated mechanism of aspirin.
Early virological response may predict treatment response in sofosbuvir-based combination therapy of chronic hepatitis c in a multi-center “real-life” cohort

The combination of sofosbuvir (SOF), ribavirin (RBV) and peg-interferon-alfa-2a (peg-IFN-alfa-2a) as well as the combination of SOF and RBV for the treatment of patients infected with hepatitis c virus (HCV) has improved rates of sustained virological response (SVR) considerably in recent trials. However, there is only limited data concerning the efficacy and safety in a "real-life" cohort.



We analyzed a cohort of 119 patients with chronic HCV infection treated at four investigational sites in Germany. All patients received either a combination treatment of SOF, RBV and peg-IFN-alfa-2a or SOF and RBV.



The rates of SVR at 12 weeks after end of treatment (SVR 12) were as follows: Among 76 patients with genotype 1 infection the SVR 12 rate was 74% (n = 56), among 14 patients with genotype 2 infection the SVR 12 rate was 79% (n = 11), among 24 patients with genotype 3 infection the SVR 12 rate was 92% (n = 22) and among 5 patients with genotype 4 infection the SVR 12 rate was 80% (n = 4). Of all 26 patients with a relapse in our cohort, 69% (n = 18) of these patients presented with liver cirrhosis and 58% (n = 15) were treatment experienced. Notably, the level of HCV-RNA after 4 weeks of treatment was a significant predictor of treatment response in genotype 1 patients. Patients with HCV-RNA levels ≥ 12 IU ml-1 after 4 weeks of treatment achieved SVR 12 only in 30% (n = 17/56, p < 0.0001) of cases and treatment response was even lower with SVR 12 of 25% (n = 5/20, p = 0.0016) in the subgroup of patients with cirrhosis.



We observed a high rate of SVR 12 with SOF-based treatment regimes, however probably due to the high number of patients with liver cirrhosis and prior treatment experience, treatment response rates were lower than in previously published trials. In genotype 1 patients the analysis of early virological response may predict treatment response in SOF-based combination therapies.
Anti-Ischaemic Response to Sublingual Nitroglycerin During Oral Administration of Isosorbide Dinitrate in Patients with Stable Angina Pectoris: When does Cross-Tolerance Occur?

The purpose of this study was to evaluate the efficacy of sublingual nitroglycerin (NTG) during treatment with oral sustained-release isosorbide dinitrate (ISDN) in two doses: 80 mg and 120 mg. In a double-blind crossover design study 38 men with stable angina initially received either an oral placebo (OP) or ISDN. All patients received either NTG 0.5 mg or sublingual placebo (SLP) 2.5 h after OP ingestion, but only NTG 2.5 h after ISDN. The same pattern was used in the first ingestion and in long-term OP or ISDN therapy for 7 days (OP and ISDN every 6 h, and ISDN once daily). The efficacy of NTG was evaluated by analyzing walking time to ischaemia (WTI) during exercise tests performed 5 minutes after NTG or SLP administration, and the efficacy of ISDN 2 h and 6 h after oral ingestion. In the first ingestion NTG significantly improved WTI (p < 0.0001) by 42.7% after OP, by 46.5% after 80 mg ISDN and by 52.1% after 120 mg. After long-term OP therapy NTG prolonged WTI (p < 0.01) by 15.6%, during once-daily ISDN treatment, an 80 mg dose prolonged WTI by 22.8% and a dose of 120 mg by 36.5%. However, NTG did not improve WTI in q.i.d. therapy. Six hours after the first 80 mg ISDN ingestion WTI improved (p < 0.0001) by 66.0%, and after 120 mg by 58.4%. Following once-daily therapy ISDN prolonged WTI (p < 0.0001) by 27.2% after an 80 mg dose and by 36.2% after a dose of 120 mg. No improvement was observed in q.i.d. treatment. Thus, severe tolerance to ISDN abolishes the anti-ischaemic effects of NTG, and appropriate regimens of ISDN have considerable anti-anginal effects during chronic administration.
Interaction between vitamin D receptor genotype and estrogen receptor alpha genotype influences vertebral fracture risk.

In view of the interactions of vitamin D and the estrogen endocrine system, we studied the combined influence of polymorphisms in the estrogen receptor (ER) alpha gene and the vitamin D receptor (VDR) gene on the susceptibility to osteoporotic vertebral fractures in 634 women aged 55 yr and older. Three VDR haplotypes (1, 2, and 3) of the BsmI, ApaI, and TaqI restriction fragment length polymorphisms and three ERalpha haplotypes (1, 2, and 3) of the PvuII and XbaI restriction fragment length polymorphisms were identified. We captured 131 nonvertebral and 85 vertebral fracture cases during a mean follow-up period of 7 yr. ERalpha haplotype 1 was dose-dependently associated with increased vertebral fracture risk (P < 0.001) corresponding to an odds ratio of 1.9 [95% confidence interval (CI), 0.9-4.1] per copy of the risk allele. VDR haplotype 1 was overrepresented in vertebral fracture cases. There was a significant interaction (P = 0.01) between ERalpha haplotype 1 and VDR haplotype 1 in determining vertebral fracture risk. The association of ERalpha haplotype 1 with vertebral fracture risk was only present in homozygous carriers of VDR haplotype 1. The risk of fracture was 2.5 (95% CI, 0.6-9.9) for heterozygous and 10.3 (95% CI, 2.7-40) for homozygous carriers of ERalpha haplotype 1. These associations were independent of bone mineral density. In conclusion, interaction between ERalpha and VDR gene polymorphisms leads to increased risk of osteoporotic vertebral fractures in women, largely independent of bone mineral density.