nils-herrmann/clean_scirepeval huggingface dataset:
A phase I dose-escalation study of danusertib (PHA-739358) administered as a 24-hour infusion with and without granulocyte colony-stimulating factor in a 14-day cycle in patients with advanced solid tumors.

This study was conducted to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of the i.v. pan-aurora kinase inhibitor PHA-739358, danusertib, in patients with advanced solid tumors.



In part 1, patients received escalating doses of danusertib (24-hour infusion every 14 days) without filgrastim (granulocyte colony-stimulating factor, G-CSF). Febrile neutropenia was the dose-limiting toxicity without G-CSF. Further dose escalation was done in part 2 with G-CSF. Blood samples were collected for danusertib pharmacokinetics and pharmacodynamics. Skin biopsies were collected to assess histone H3 phosphorylation (pH3).



Fifty-six patients were treated, 40 in part 1 and 16 in part 2. Febrile neutropenia was the dose-limiting toxicity in part 1 without G-CSF. Most other adverse events were grade 1 to 2, occurring at doses >or=360 mg/m(2) with similar incidence in parts 1 and 2. The maximum tolerated dose without G-CSF is 500 mg/m(2). The recommended phase 2 dose in part 2 with G-CSF is 750 mg/m(2). Danusertib showed dose-proportional pharmacokinetics in parts 1 and 2 with a median half-life of 18 to 26 hours. pH3 modulation in skin biopsies was observed at >or=500 mg/m(2). One patient with refractory small cell lung cancer (1,000 mg/m(2) with G-CSF) had an objective response lasting 23 weeks. One patient with refractory ovarian cancer had 27% tumor regression and 30% CA125 decline.



Danusertib was well tolerated with target inhibition in skin at >or=500 mg/m(2). Preliminary evidence of antitumor activity, including a partial response and several occurrences of prolonged stable disease, was seen across a variety of advanced refractory cancers. Phase II studies are ongoing.
International multicentre prospective study on microwave ablation of liver tumours: preliminary results.

Microwave ablation (MWA) is increasingly utilized in the treatment of hepatic tumours. Promising single-centre reports have demonstrated its safety and efficacy, but this modality has not been studied in a prospective, multicentre study.



Eighteen international centres recorded operative and perioperative data for patients undergoing MWA for tumours of any origin in a voluntary Internet-based database. All patients underwent operative MWA using a 2.45-GHz generator with a 5-mm antenna.



Of the 140 patients, 114 (81.4%) were treated with MWA alone and 26 (18.6%) were treated with MWA combined with resection. Multiple tumours were treated with MWA in 40.0% of patients. A total of 299 tumours were treated in these 140 patients. The median size of ablated lesions was 2.5 cm (range: 0.5-9.5 cm). Tumours were treated with a median of one application (range: 1-6 applications) for a median of 4 min (range: 0.5-30.0 min). A power setting of 100 W was used in 78.9% of cases. Major morbidity was 8.3% and in-hospital mortality was 1.9%.



These multi-institution data demonstrate rapid ablation time and low morbidity and mortality rates in patients undergoing operative MWA with a high rate of multiple ablations and concomitant hepatic resection. Longterm follow-up will be required to determine the efficacy of MWA relative to other forms of ablative therapy.
A comparative evaluation of propofol and midazolam as sedative agents in fiberoptic bronchoscopy.

Propofol, a new intravenous sedative agent, was investigated in 41 asthmatic patients undergoing day-case (outpatient) fiberoptic bronchoscopy. The study design was a randomized comparison between propofol and midazolam, which is a well-established intravenous sedative agent. The age, weight, and American Society of Anesthesiologists physical status and lung function of the two groups were not significantly different. Mean (SD) induction dose of propofol was 104.7 (30.1) mg with a maintenance dose of 121.9 (38.5) mg. Corresponding values of midazolam were 9.3 (3.1) mg and 3.7 (2.3) mg. The required level of sedation was achieved significantly faster with propofol, mean (SD) 125.4 (39.8) s, compared with midazolam, 179.4 (55.2) s (p < 0.001). Significantly faster recovery was noted with propofol compared with midazolam in terms of time to recall name and date of birth 2.3 (1.7) min vs 6.3 (8.6) min, (p < 0.045). Alertness scored with the digital symbol substitution test (DSST) returned to prebronchoscopy values in the propofol group at 30 min, DSST score = 35.9 (18.2) vs 13.4 (9.1), in the midazolam group (p < .0001) and was still significantly higher at 90 min-39.4 (17.9) and 23.1 (13.8) (p < 0.01). We conclude that propofol is a useful sedating agent in fiberoptic bronchoscopy with similar efficacy to midazolam but with a faster onset of action and a more rapid recovery. These represent significant advantages for day-case procedures.
Processing mode during repetitive thinking in socially anxious individuals: evidence for a maladaptive experiential mode.

Evidence from the depression literature suggests that an analytical processing mode adopted during repetitive thinking leads to maladaptive outcomes relative to an experiential processing mode. To date, in socially anxious individuals, the impact of processing mode during repetitive thinking related to an actual social-evaluative situation has not been investigated. We thus tested whether an analytical processing mode would be maladaptive relative to an experiential processing mode during anticipatory processing and post-event rumination.



High and low socially anxious participants were induced to engage in either an analytical or experiential processing mode during: (a) anticipatory processing before performing a speech (Experiment 1; N = 94), or (b) post-event rumination after performing a speech (Experiment 2; N = 74). Mood, cognition, and behavioural measures were employed to examine the effects of processing mode.



For high socially anxious participants, the modes had a similar effect on self-reported anxiety during both anticipatory processing and post-event rumination. Unexpectedly, relative to the analytical mode, the experiential mode led to stronger high standard and conditional beliefs during anticipatory processing, and stronger unconditional beliefs during post-event rumination.



These experiments are the first to investigate processing mode during anticipatory processing and post-event rumination. Hence, these results are novel and will need to be replicated.



These findings suggest that an experiential processing mode is maladaptive relative to an analytical processing mode during repetitive thinking characteristic of socially anxious individuals.
Stinging nettle cream for osteoarthritis.

Stinging Nettle Cream for Osteoarthritis Keith Rayburn, MD, is a physician in the Department of Medicine, Santa Clara Valley Medical Center, San Jose, California. Eric Fleischbein, PharmD, is a pharmacist in the Department of Pharmacy Services, Santa Clara Valley Medical Center. Jessica Song, PharmD, is a pharmacist in the Department of Pharmacy Services, Santa Clara Valley Medical Center, and an instructor at the University of the Pacifi c Thomas J. Long School of Pharmacy and Health Sciences, Stockton, California. Blaine Allen, RN, is a nurse in the Department of Nursing, Santa Clara Valley Medical Center. Mary Kundert, PharmD, and Charles Leiter, PharmD, are pharmacists at Leiter’s Pharmacy, San Jose. Thomas Bush, MD, is a physician in the Department of Medicine, Santa Clara Valley Medical Center.
‘HeART of Stroke (HoS)’, a community-based Arts for Health group intervention to support self-confidence and psychological well-being following a stroke: protocol for a randomised controlled feasibility study

Over 152,000 people in the UK have strokes annually and a third experience residual disability. Low mood also affects a third of stroke survivors; yet psychological support is poor. While Arts for Health interventions have been shown to improve well-being in people with mild-to-moderate depression post-stroke, their role in helping people regain sense of self, well-being and confidence has yet to be evaluated. The main aim of this study is to explore the feasibility of conducting a pragmatic multicentre randomised controlled trial to assess the effectiveness and cost-effectiveness of an Arts for Health group intervention ('HeART of Stroke' (HoS)) for stroke survivors. HoS is a 10-session artist-facilitated group intervention held in the community over 14 weeks. It offers a non-judgemental, supportive environment for people to explore sense of self, potentially enhancing well-being and confidence.



Sixty-four people, up to 2 years post-stroke, recruited via secondary care research staff or community stroke/rehabilitation teams in two UK centres will be randomised to either HoS plus usual care or usual care only. Self-reported outcomes, measured at baseline and approximately 5 months postrandomisation, will include stroke-related, well-being, mood, self-esteem, quality of life and process measures. Analyses will focus on estimating key feasibility parameters (eg, rates of recruitment, retention, intervention attendance). We will develop outcome and resource use data collection methods to inform an effectiveness and cost-effectiveness analysis in the future trial. Interviews, with a sample of participants, will explore the acceptability of the intervention and study processes, as well as experiences of the HoS group.


ETHICS AND DISSEMINATION
National Health Service (NHS), Research and Development and University ethical approvals have been obtained. Two peer-reviewed journal publications are planned plus one service user led publication. Findings will be disseminated at key national conferences, local stakeholder events and via institutional websites.
Nasal Mucociliary Clearance in Subjects With COPD After Smoking Cessation.

Exposure to cigarette smoke causes significant impairment in mucociliary clearance (MCC), which predisposes patients to secretion retention and recurrent airway infections that play a role in exacerbations of COPD. To determine whether smoking cessation may influence MCC and frequency of exacerbations, the following groups were evaluated: ex-smokers with COPD, smokers with COPD, current smokers with normal lung function, and nonsmokers with normal lung function.



Ninety-three subjects were divided into 4 groups: ex-smokers with COPD (n = 23, 62.4 ± 8.0 y, 13 males), smokers with COPD (n = 17, 58.2 ± 8.0 y, 6 males), current smokers (n = 27, 61.5 ± 6.4 y, 17 males), and nonsmokers (n = 26, 60.8 ± 11.3 y, 7 males). MCC was evaluated using the saccharin transit time (STT) test, and the frequency of exacerbations in the last year was assessed by questionnaire. The Kruskal-Wallis test followed by Dunn's test were used to compare STT among groups, and the Goodman test was used to compare the frequency of exacerbations.



STT of smokers with COPD (16.5 [11-28] min; median [interquartile range 25-75%]) and current smokers (15.9 [10-27] min) was longer compared with ex-smokers with COPD (9.7 [6-12] min) and nonsmokers (8 [6-16] min) (P < .001). There was no difference in STT values between smokers with COPD and current smokers, and these values in ex-smokers with COPD were similar to the control group (P > .05). The frequency of exacerbations was lower in ex-smokers with COPD compared with smokers with COPD.



One year after smoking cessation, subjects with COPD had improved mucociliary clearance.
Wavelet analysis of instantaneous heart rate: a study of autonomic control during thrombolysis.

Myocardial infarction (MI) is known to elicit activation of the autonomic nervous system. Reperfusion, induced by thrombolysis, is thus expected to bring about a shift in the balance between the sympathetic and vagal systems, according to the infarct location. In this study, we explored the correlation between reperfusion and the spectral components of heart rate (HR) variability (HRV), which are associated with autonomic cardiac control. We analyzed the HR of patients during thrombolysis: nine anterior wall MI (AW-MI) and eight inferoposterior wall MI (IW-MI). Reperfusion was determined from changes in ST levels and reported pain. Reocclusion was detected in four patients. HRV was analyzed using a modified continuous wavelet transform, which provided time-dependent versions of the typically used low-frequency (LF) and high-frequency (HF) peaks and of their ratio, LF/HF. Marked alterations in at least one of the HRV parameters was found in all 18 reperfusion events. Patterns of HRV, compatible with a shift toward relative sympathetic enhancement, were found in all of the nine reperfusion events in IW-MI patients and in three AW-MI patients. Patterns of HRV compatible with relative vagal enhancement were found in six AW-MI patients (P < 0.001). Significant changes in HRV parameters were also found after reocclusion. Time-dependent spectral analysis of HRV using the wavelet transform was found to be valuable for explaining the patterns of cardiac rate control during reperfusion. In addition, examination of the entire record revealed epochs of markedly diminished HRV in two patients, which we attribute to vagal saturation.
Learning API Usages from Bytecode: A Statistical Approach

Mobile app developers rely heavily on standard API frameworks and libraries. However, learning API usages is often challenging due to the fast-changing nature of API frameworks for mobile systems and the insufficiency of API documentation and source code examples. In this paper, we propose a novel approach to learn API usages from bytecode of Android mobile apps. Our core contributions include HAPI, a statistical model of API usages and three algorithms to extract method call sequences from apps' bytecode, to train HAPI based on those sequences, and to recommend method calls in code completion using the trained HAPIs. Our empirical evaluation shows that our prototype tool can effectively learn API usages from 200 thousand apps containing 350 million method sequences. It recommends next method calls with top-3 accuracy of 90% and outperforms baseline approaches on average 10--20%.
IGF-I treatment in adults with type 1 diabetes: effects on glucose and protein metabolism in the fasting state and during a hyperinsulinemic-euglycemic amino acid clamp.

Type 1 diabetes is associated with abnormalities of the growth hormone (GH)-IGF-I axis. Such abnormalities include decreased circulating levels of IGF-I. We studied the effects of IGF-I therapy (40 microg x kg(-1) x day(-1)) on protein and glucose metabolism in adults with type 1 diabetes in a randomized placebo-controlled trial. A total of 12 subjects participated, and each subject was studied at baseline and after 7 days of treatment, both in the fasting state and during a hyperinsulinemic-euglycemic amino acid clamp. Protein and glucose metabolism were assessed using infusions of [1-13C]leucine and [6-6-2H2]glucose. IGF-I administration resulted in a 51% rise in circulating IGF-I levels (P < 0.005) and a 56% decrease in the mean overnight GH concentration (P < 0.05). After IGF-I treatment, a decrease in the overnight insulin requirement (0.26+/-0.07 vs. 0.17+/-0.06 U/kg, P < 0.05) and an increase in the glucose infusion requirement were observed during the hyperinsulinemic clamp (approximately 67%, P < 0.05). Basal glucose kinetics were unchanged, but an increase in insulin-stimulated peripheral glucose disposal was observed after IGF-I therapy (37+/-6 vs. 52+/-10 micromol x kg(-1) x min(-1), P < 0.05). IGF-I administration increased the basal metabolic clearance rate for leucine (approximately 28%, P < 0.05) and resulted in a net increase in leucine balance, both in the basal state and during the hyperinsulinemic amino acid clamp (-0.17+/-0.03 vs. -0.10+/-0.02, P < 0.01, and 0.25+/-0.08 vs. 0.40+/-0.06, P < 0.05, respectively). No changes in these variables were recorded in the subjects after administration of placebo. These findings demonstrated that IGF-I replacement resulted in significant alterations in glucose and protein metabolism in the basal and insulin-stimulated states. These effects were associated with increased insulin sensitivity, and they underline the major role of IGF-I in protein and glucose metabolism in type 1 diabetes.
The effect of interleukin-1 blockade on fatigue in rheumatoid arthritis—a pilot study

Fatigue occurs in many patients with rheumatoid arthritis (RA) and other chronic inflammatory diseases and may be defined as an overwhelming sense of tiredness, lack of energy, and feeling of exhaustion. It can be restrictive and severely disabling. We recently found more than 3/4 of systemic lupus erythematosus patients to be significantly affected by this phenomenon. We hypothesized that fatigue in patients with RA might be comparable to sickness behavior in animals possibly caused by disturbances in interleukin-1 beta signaling pathways and thus accessible to blockade by biologic agents. This study compared measures of disease behavior and fatigue symptoms in eight RA patients before and at three time points during treatment with daily administration of anakinra.
Lithotomy and Extraction of Stone

This large and handsome volume describes lithotomy only, no mention being made of lithotrity ; and is a compilation of the most innocent and naive character. Without the slightest pretensions to original observation or research, the author has bundled together in a tolerably well-arranged manner the data on the subject of lithotomy from a few of the most familiar works on surgery in the English language. He has apparently arranged these fragments under different heads in a common-place book, and then persuaded
Cost analysis of a randomized stem cell mobilization study in multiple myeloma

Upfront autologous stem cell transplantation (ASCT) is the standard therapy for younger multiple myeloma (MM) patients. MM patients usually undergo stem cell mobilization with cyclophosphamide (CY) followed by granulocyte colony-stimulating factor (G-CSF), or with G-CSF alone. A limited number of randomized studies are available comparing costs of different mobilization strategies. Eighty transplant-eligible patients aged up to 70 years with untreated MM were included in this prospective study. The patients were treated with RVD induction for three 21-day cycles and randomized 1:1 at inclusion into one of the two mobilization arms CY 2 g/m2 + G-CSF [arm A] vs. G-CSF alone [arm B]. Plerixafor was given according to a specific algorithm if needed. Sixty-nine patients who received mobilization followed by blood graft collection were included in the cost analysis. The median total costs of the mobilization phase were significantly higher in arm A than in arm B (3855 € vs. 772 €, p ≤ 0.001). The cumulative median cost of the mobilization and collection phases was significantly lower in arm B than in arm A (8524 € vs. 11,622 €, p = 0.012). There was no significant difference between the arms in the total median costs of ASCT (n = 59) (34,997 € in arm A vs. 31,981 € in arm B, p = 0.118). Mobilization with G-CSF alone seems to be a preferable mobilization method for MM patients in terms of mobilization and apheresis costs. In addition, it requires less hospital resource utilization.
Obese Patients With a Binge Eating Disorder Have an Unfavorable Metabolic and Inflammatory Profile

To evaluate whether obese patients with a binge eating disorder (BED) have an altered metabolic and inflammatory profile related to their eating behaviors compared with non-BED obese.A total of 115 White obese patients consecutively recruited underwent biochemical, anthropometrical evaluation, and a 75-g oral glucose tolerance test. Patients answered the Binge Eating Scale and were interviewed by a psychiatrist. The patients were subsequently divided into 2 groups according to diagnosis: non-BED obese (n = 85) and BED obese (n = 30). Structural equation modeling analysis was performed to elucidate the relation between eating behaviors and metabolic and inflammatory profile.BED obese exhibited significantly higher percentages of altered eating behaviors, body mass index (P < 0.001), waist circumference (P < 0.01), fat mass (P < 0.001), and a lower lean mass (P < 0.001) when compared with non-BED obese. Binge eating disorder obese also had a worse metabolic and inflammatory profile, exhibiting significantly lower high-density lipoprotein cholesterol levels (P < 0.05), and higher levels of glycated hemoglobin (P < 0.01), uric acid (P < 0.05), erythrocyte sedimentation rate (P < 0.001), high-sensitive C-reactive protein (P < 0.01), and white blood cell counts (P < 0.01). Higher fasting insulin (P < 0.01) and higher insulin resistance (P < 0.01), assessed by homeostasis model assessment index and visceral adiposity index (P < 0.001), were observed among BED obese. All differences remained significant after adjusting for body mass index. No significant differences in fasting plasma glucose or 2-hour postchallenge plasma glucose were found. Structural equation modeling analysis confirmed the relation between the altered eating behaviors of BED and the metabolic and inflammatory profile.Binge eating disorder obese exhibited an unfavorable metabolic and inflammatory profile, which is related to their characteristic eating habits.
Prostate-specific antigen and free prostate-specific antigen in the early detection of prostate cancer: do combination tests improve detection?

The combined use of free and total prostate-specific antigen (PSA) in early detection of prostate cancer has been controversial. This article systematically evaluates the discriminating capacity of a large number of combination tests.



Free and total PSA were analyzed in stored serum samples taken prior to diagnosis in 429 cases and 1,640 controls from the Physicians' Health Study. We used a classification algorithm called logic regression to search for clinically useful tests combining total and percent free PSA and receiver operating characteristic analysis and compared these tests with those based on total and complexed PSA. Data were divided into training and test subsets. For robustness, we considered 35 test-train splits of the original data and computed receiver operating characteristic curves for each test data set.



The average area under the receiver operating characteristic curve across test data sets was 0.74 for total PSA and 0.76 for the combination tests. Combination tests with higher sensitivity and specificity than PSA > 4.0 ng/mL were identified 29 out of 35 times. All these tests extended the PSA reflex range to below 4.0 ng/mL. Receiver operating characteristic curve analysis indicated that the overall diagnostic performance as expressed by the area under the curve did not differ significantly for the different tests.



Tests combining total and percent free PSA show modest overall improvements over total PSA. However, utilization of percent free PSA below a PSA threshold of 4 ng/mL could translate into a practically important reduction in unnecessary biopsies without sacrificing cancers detected.