nils-herrmann/clean_scirepeval huggingface dataset:
Fluid sketching of directed graphs

We describe a prototype sketch-based system that allows users to draw and manipulate directed graphs using gestural input exclusively. The system incorporates the notion of fluid sketching, which attempts to recognize and beautify what the user is drawing while it is being drawn. This concept applies to both the drawing of vertices, which are morphed to circles, and to the drawing of edges, which are approximated on-the-fly by a constrained projection onto low-order polynomials. Consequently, all user-drawn strokes are cleaned up by continuously morphing or projecting them to the nearest geometrically precise shapes. The system has a unique look and feel in that the currently-displayed graph is always at or in transition toward a clean and precise representation of what the user has drawn or is in the process of drawing. When vertices of the graph are dragged to new locations or edges are reshaped, the original graph connectivity is maintained while simultaneously retaining some of its original user-drawn character, such as vertex size and placement, and overall edge shape.
Treatment satisfaction with zolmitriptan nasal spray for migraine in a real life setting: results from phase two of the REALIZE study

In phase one of the REALIZE study, zolmitriptan nasal spray demonstrated a significant headache response from 10 min post–dose and total symptom relief from 30 min post–dose. The objective of phase two was to investigate patients' dosing patterns, satisfaction and preference following openlabel treatment with the nasal spray. Up to 3 attacks were treated. The ITT population consisted of 851 patients. The median time from onset of symptoms to treatment was 1 h 15 min (primary endpoint). Most patients reported being satisfied or very satisfied with zolmitriptan nasal spray (75.7%). Furthermore, the majority of patients would be willing to use zolmitriptan nasal spray in the future (59.8%) and preferred zolmitriptan nasal spray over previous therapies (57.8%). Zolmitriptan nasal spray was well tolerated. Most patients were satisfied with zolmitriptan nasal spray, were willing to continue using it and preferred it to previous therapies.
Intravenous ibandronate injections given every three months: a new treatment option to prevent bone loss in postmenopausal women.

To investigate the efficacy, safety, and dose response of three doses of ibandronate, given intermittently by intravenous (IV) injection every three months, in preventing postmenopausal osteoporosis.



629 postmenopausal women, categorised according to time since menopause and baseline lumbar spine (L1-4) bone mineral density (BMD), were enrolled into a multicentre, double blind, placebo controlled trial. They were randomly allocated to receive IV ibandronate 0.5 mg, 1 mg or 2 mg, or placebo every three months. All women received daily calcium supplementation.



One year's treatment with intermittent IV ibandronate injections produced a dose dependent gain in mean (SD) lumbar spine BMD from baseline of 2.5 (2.5)%, 1.8 (2.6)%, and 1.0 (2.8)% in the groups receiving 2 mg, 1 mg, and 0.5 mg ibandronate, respectively, compared with a loss of BMD of 0.4 (2.4)% in the women in the placebo group; p=0.0001 for each ibandronate dose v placebo. Highest BMD gains occurred in women with osteopenia receiving 2 mg ibandronate. Similarly, at the hip, all three doses of ibandronate produced significantly better gains in BMD than placebo (p<0.05), with the greatest gains in the women with osteopenia receiving the 2 mg dose. Ibandronate concomitantly and dose dependently suppressed markers of bone turnover in comparison with placebo, and injections were well tolerated.



IV ibandronate injections, given every three months, may be an effective alternative to oral bisphosphonates and hormonal therapy in the prevention of bone loss in postmenopausal women.
Neural predictors and mechanisms of cognitive behavioral therapy on threat processing in social anxiety disorder

Cognitive behavioral therapy (CBT) is "gold standard" psychotherapy for social anxiety disorder (SAD). Cognitive models posit that preferential processing of threat mediates excessive forms of anxiety, which is supported by exaggerated amygdala, insula, and cortical reactivity to threatening socio-emotional signals in SAD. However, little is known about neural predictors of CBT success or the mechanisms by which CBT exerts its therapeutic effects. Functional magnetic resonance imaging (fMRI) was conducted during responses to social signals of threat (fearful/angry faces) against positive signals (happy faces) in 14 patients with SAD before and after 12 weeks of CBT. For comparison, 14 healthy control (HC) participants also underwent two fMRI scans, 12 weeks apart. Whole-brain voxel-wise analyses showed therapeutic success was predicted by enhanced pre-treatment activation to threatening faces in higher-order visual (superior and middle temporal gyrus), cognitive, and emotion processing areas (dorsal anterior cingulate cortex, dorsomedial prefrontal cortex). Moreover, a group by time interaction was revealed in prefrontal regions (dorsomedial, medial gyrus) and insula. The interaction was driven by relatively greater activity during threat processing in SAD, which significantly reduced after CBT but did not significantly predict response to CBT. Therefore, pre-treatment cortical hyperactivity to social threat signals may serve as a prognostic indicator of CBT success in SAD. Collectively, CBT-related brain changes involved a reduction in activity in insula, prefrontal, and extrastriate regions. Results are consistent with cognitive models, which associate decreases in threat processing bias with recovery.
Phase I study of cediranib in combination with oxaliplatin and infusional 5-Fluorouracil in patients with advanced colorectal cancer.

Cediranib is a potent oral inhibitor of the tyrosine kinase activity associated with all subtypes of vascular endothelial growth factor receptor. Purposes of this study were to determine the recommended phase II dose of cediranib in combination with standard doses of modified FOLFOX-6 (mFOLFOX-6), and the tolerability, safety, pharmacokinetics, and antitumor activity of this combination in patients with untreated metastatic colorectal cancer.



Cediranib was administered daily orally at a starting dose of 30 mg and escalated to 45 mg daily, and mFOLFOX-6 was repeated every 14 days. Pharmacokinetic studies were done for oxaliplatin, 5-fluorouracil, and cediranib. Response was assessed by Response Evaluation Criteria in Solid Tumors every four cycles.



Sixteen patients received 150 cycles of treatment (median, 6; range, 1-20 cycles). Of 9 patients enrolled at the 30-mg dose level, 1 patient experienced grade 3 diarrhea during cycle 1. No dose-limiting toxicity was observed in 7 patients at the 45-mg dose level. Common grade 3 toxicities related to cediranib included hypertension, diarrhea, fatigue, and anorexia. Of 14 patients evaluable for response, there were 6 partial responses (42.9%; 95% confidence interval, 17.7-71.1%) and 6 stable disease. The median progression-free survival was 9.3 months. There were no pharmacokinetic interactions between cediranib and 5-fluorouracil or free plasma intact oxaliplatin.



Toxicities of this combination were manageable and consistent with previous studies. The recommended phase II dose is cediranib at 30 mg daily continuously in combination with standard doses of mFOLFOX-6. Cediranib and mFOLFOX-6 has promising antitumor activity and this combination warrants further investigation.
Combinatorial gene regulation by modulation of relative pulse timing

Studies of individual living cells have revealed that many transcription factors activate in dynamic, and often stochastic, pulses within the same cell. However, it has remained unclear whether cells might exploit the dynamic interaction of these pulses to control gene expression. Here, using quantitative single-cell time-lapse imaging of Saccharomyces cerevisiae, we show that the pulsatile transcription factors Msn2 and Mig1 combinatorially regulate their target genes through modulation of their relative pulse timing. The activator Msn2 and repressor Mig1 showed pulsed activation in either a temporally overlapping or non-overlapping manner during their transient response to different inputs, with only the non-overlapping dynamics efficiently activating target gene expression. Similarly, under constant environmental conditions, where Msn2 and Mig1 exhibit sporadic pulsing, glucose concentration modulated the temporal overlap between pulses of the two factors. Together, these results reveal a time-based mode of combinatorial gene regulation. Regulation through relative signal timing is common in engineering and neurobiology, and these results suggest that it could also function broadly within the signalling and regulatory systems of the cell.
A phase I study of histone deacetylase inhibitor, pracinostat (SB939), in pediatric patients with refractory solid tumors: IND203 a trial of the NCIC IND program/C17 pediatric phase I consortium.

Pracinostat (SB939) is a potent oral inhibitor of class 1, 2, and 4 histone deacetylases (HDAC). The adult recommended phase II dose (RP2D) is 60 mg po three times per week (t.i.w.) for 3 weeks every 4 weeks. This study assessed the toxicities and pharmacokinetics of pracinostat and determined the RP2D in children with refractory solid tumors.



Pediatric patients with refractory solid tumors were treated with oral pracinostat t.i.w. for 3 consecutive weeks, followed by 1 week off dosing. Three dose levels-25, 35, and 45 mg/m(2) were evaluated using a standard 3 + 3 cohort design. Pharmacokinetic (PK) studies were optional.



Twelve patients were enrolled. The most common diagnosis was Ewing sarcoma. Most adverse events (AEs) were hematological with five (40%) patients experiencing grade 3 neutropenia. Non-hematological AEs were generally grade 1. No dose limiting toxicities occurred. More hematological and non-hematological AEs occurred at 45 mg/m(2) : Two of five patients experienced Grade 3 neutropenia and one each Grade 3 thrombocytopenia and leucopenia, Grade 1 fatigue and anorexia occurred in three. The RP2D was declared to be 45 mg/m(2) (comparable to an adult dose of 80 mg). One patient had a best response of stable disease (duration of 2.9 months). Three patients on 25 mg/m(2) and one each on 35 and 45 mg/m(2) participated in the PK study. No dose related changes in Cmax or AUC occurred.



Pracinostat is reasonably well tolerated in children with refractory solid tumors. The RP2D is 45 mg/m(2) .
Large loop versus straight-wire excision of the transformation zone for treatment of cervical intraepithelial neoplasia: a randomised controlled trial of electrosurgical techniques.

To compare two electrosurgical techniques, straight-wire excision of transformation zone (SWETZ) with large loop excision of transformation zone, as a cone procedure (LLETZ-cone), for the treatment of cervical intraepithelial neoplasia (CIN), when disease is present at the cervical canal.



Randomised controlled trial.



Two public hospitals, one in Rio de Janeiro, Brazil and one in Dublin, Ireland.



One hundred and three women with indication to treat CIN located at cervical canal.



Women were randomised to receive LLETZ-cone or SWETZ.



Main outcome was the incidence of complete excision of disease at endocervical margin of the surgical specimen. Secondary outcomes were complete excision at ectocervical and stromal margins, time to complete the procedure, specimen fragmentation, blood loss and death after 1 year.



Fifty-two women were allocated to LLETZ-cone and 51 to SWETZ. Ten women were lost for main outcome because of damaged specimens. Forty-two women in the LLETZ-cone group had free endocervical margin versus 43 women in the SWETZ group (relative risk 1.04, 95% confidence interval [95% CI] 0.87-1.25; P = 0.64). For secondary outcomes related to margins, we observed a relative risk of 1.15 (95% CI 0.95-1.39; P = 0.15) for ectocervical free margin. For free stromal margin, the relative risk was 1.07 (95% CI 0.89-1.29; P = 0.47). No death was observed.



This study was inconclusive; SWETZ and LLETZ-cone were equally effective to treat endocervical disease, with no difference in protecting against margin involvement. Higher, but not severe, blood loss and longer surgical time were observed in the SWETZ group.
Impact of Chemotherapy Beyond the Third Line in Patients With Recurrent Epithelial Ovarian Cancer.

The goal of this study was to determine the benefit in terms of time disease control (TDC) achieved by the succession of chemotherapy beyond the third line in patients treated for recurrent epithelial ovarian cancer. Secondary objectives were to identify patients who benefited from treatments beyond 3 lines and to estimate overall survival and disease-free progression lengths.



The cohort of 122 patients was identified from a pharmacy database of patients treated with chemotherapy between 1992 and 2010. The evaluation of benefit obtained by each line was based on TDC duration, defined as the interval between the beginning of the treatment and the date of progressive disease or death.



Median TDC durations was 4.15 (0-54.7), 4 (0-21.7), 3.34 (0-29.6), 4.97 (0-29.2), and 3.13 months (0-15) for the fourth to eighth lines, respectively. Time to disease control was longer than 6 months in 34% to 40% of patients treated by lines 4 to 8. The most important factor influencing TDC length beyond the third line was the TDC duration observed in the 2 previous lines of therapy. Median overall survival after the third line was 15.3 months (95% confidence interval, 12-20 months). Factors associated with longer overall survival after 3 lines were performance status lower than 2 (P = 0.0058), no hepatic metastasis (P = 0.0098), no pulmonary metastasis (P = 0.0003), and platinum sensitivity (P = 0.04)  These results may justify the administration of chemotherapy beyond the third line, in particular when the 2 previous lines are effective and resulted in disease control longer than 6 months.
The effect of kinematic and kinetic changes on meniscal strains during gait.

The menisci play an important role in load distribution, load bearing, joint stability, lubrication, and proprioception. Partial meniscectomy has been shown to result in changes in the kinematics and kinetics at the knee during gait that can lead to progressive meniscal degeneration. This study examined changes in the strains within the menisci associated with kinematic and kinetic changes during the gait cycle. The gait changes considered were a 5 deg shift toward external rotation of the tibia with respect to the femur and an increased medial-lateral load ratio representing an increased adduction moment. A finite element model of the knee was developed and tested using a cadaveric specimen. The cadaver was placed in positions representing heel-strike and midstance of the normal gait, and magnetic resonance images were taken. Comparisons of the model predictions to boundaries digitized from images acquired in the loaded states were within the errors produced by a 1 pixel shift of either meniscus. The finite element model predicted that an increased adduction moment caused increased strains of both the anterior and posterior horns of the medial meniscus. The lateral meniscus exhibited much lower strains and had minimal changes under the various loading conditions. The external tibial rotational change resulted in a 20% decrease in the strains in the posterior medial horn and increased strains in the anterior medial horn. The results of this study suggest that the shift toward external tibial rotation seen clinically after partial medial meniscectomy is not likely to cause subsequent degenerative medial meniscal damage, but the consequence of this kinematic shift on the pathogenesis of osteoarthritis following meniscectomy requires further consideration.
Characteristics of youth seeking emergency care for assault injuries.

To characterize youth seeking care for assault injuries, the context of violence, and previous emergency department (ED) service utilization to inform ED-based injury prevention.



A consecutive sample of youth (14-24) presenting to an urban ED with an assault injury completed a survey of partner violence, gun/knife victimization, gang membership, and context of the fight.



A total of 925 youth entered the ED with an assault injury; 718 completed the survey (15.4% refused); 730 comparison youth were sampled. The fights leading to the ED visit occurred at home (37.6%) or on streets (30.4%), and were commonly with a known person (68.3%). Fights were caused by issues of territory (23.3%) and retaliation (8.9%); 20.8% of youth reported substance use before the fight. The assault-injured group reported more peer/partner violence and more gun experiences. Assault-injured youth reported higher past ED utilization for assault (odds ratio [OR]: 2.16) or mental health reasons (OR: 7.98). Regression analysis found the assault-injured youth had more frequent weapon use (OR: 1.25) and substance misuse (OR: 1.41).



Assault-injured youth seeking ED care report higher levels of previous violence, weapon experience, and substance use compared with a comparison group seeking care for other complaints. Almost 10% of assault-injured youth had another fight-related ED visit in the previous year, and ~5% had an ED visit for mental health. Most fights were with people known to them and for well-defined reasons, and were therefore likely preventable. The ED is a critical time to interact with youth to prevent future morbidity.
High-density lipoprotein restores endothelial function in hypercholesterolemic men.

Hypercholesterolemia is a risk factor for atherosclerosis-causing endothelial dysfunction, an early event in the disease process. In contrast, high-density lipoprotein (HDL) cholesterol inversely correlates with morbidity and mortality representing a protective effect. Therefore, we investigated the effects of reconstituted HDL on endothelial function in hypercholesterolemic men.



Endothelium-dependent and -independent vasodilation to intraarterial acetylcholine and sodium nitroprusside (SNP), respectively, was measured by forearm venous occlusion plethysmography in healthy normo- and hypercholesterolemic men. In hypercholesterolemics, the effects of reconstituted HDL (rHDL; 80 mg/kg IV over 4 hours) on acetylcholine- and SNP-induced changes in forearm blood flow were assessed in the presence or absence of the nitric oxide (NO) synthase inhibitor L-NMMA. Hypercholesterolemics showed reduced vasodilation to acetylcholine but not to SNP compared with normocholesterolemics (P<0.0001). rHDL infusion increased plasma HDL cholesterol from 1.3+/-0.1 to 2.2+/-0.1 mmol/L (P<0.0001, n=18) and significantly enhanced the acetylcholine-induced increase in forearm blood flow without affecting that induced by SNP. rHDL infusion also improved flow-mediated dilation of the brachial artery (to 4.5+/-0.9% from 2.7+/-0.6%, P=0.02). NO synthase inhibition prevented the improvement in acetylcholine-induced vasodilation while leaving the response to SNP unchanged. Albumin infusion in an equivalent protein dose had no effect on vasomotion or lipid levels.



In hypercholesterolemic patients, intravenous rHDL infusion rapidly normalizes endothelium-dependent vasodilation by increasing NO bioavailability. This may in part explain the protective effect of HDL from coronary heart disease and illustrates the potential therapeutic benefit of increasing HDL in patients at risk from atherosclerosis.
Body Mass Index at Diagnosis and Breast Cancer Survival Prognosis in Clinical Trial Populations from NRG Oncology/NSABP B-30, B-31, B-34, and B-38.

Body mass index (BMI) has been associated with breast cancer outcomes. However, few studies used clinical trial settings where treatments and outcomes are consistently evaluated and documented. There are also limited data assessing how patient/disease characteristics and treatment may alter the BMI-breast cancer association.



We evaluated 15,538 breast cancer participants from four NSABP protocols. B-34 studied early-stage breast cancer patients (N = 3,311); B-30 and B-38 included node-positive breast cancer patients (N = 5,265 and 4,860); and B-31 studied node-positive and HER2-positive breast cancer patients (N = 2,102). We used Cox proportional hazards regression to calculate adjusted hazards ratios (HR) for risk of death and recurrence, and conducted separate analyses by estrogen receptor (ER) status and treatment group.



In B-30, increased BMI was significantly related to survival. Compared with BMI < 25, HRs were 1.04 for BMI 25 to 29.9 and 1.18 for BMI ≥ 30 (P = 0.02). Separate analyses indicated the significant relationship was only in ER-positive disease (P = 0.002) and the subgroup treated with doxorubicin/cyclophosphamide (P = 0.005). There were no significant trends across BMI for the other three trials. Similar results were found for recurrence. Increased BMI was significantly related to recurrence in B-30 (P = 0.03); and the significant relationship was only in ER-positive breast cancers (P = 0.001). Recurrence was also significant among ER-positive disease in B-38 (P = 0.03).



In our investigation, we did not find a consistent relationship between BMI at diagnosis and breast cancer recurrence or death.



This work demonstrates that the heterogeneity of breast cancer between different breast cancer populations and the different therapies used to treat them may modify any association that exists between BMI and breast cancer outcome.
Cardiovascular effects of nasal and transdermal nicotine and cigarette smoking.

The purpose of this study was to compare circadian blood pressure and heart rate patterns and other cardiovascular effects of nicotine delivered rapidly (via nasal spray, NNS), slowly (transdermal nicotine, TDN), by cigarette smoking (rapid delivery of nicotine plus other smoke toxins), and placebo NNS. Twelve healthy cigarette smokers were studied on a research ward when they smoked cigarettes (16 per day) or used TDN (15 mg/16 h), NNS (24 1-mg doses per day), or placebo NNS, each for 5 days. There were no significant differences in systolic blood pressure, but diastolic blood pressure was slightly increased during cigarette smoking. Plasma epinephrine, beta-thromboglobulin, and fibrinogen levels were higher during cigarette smoking than with TDN. For most measurements, NNS values were intermediate between and not significantly different from those of cigarette smoking and TDN. We conclude that, at recommended doses, TDN and NNS have fewer effects on biomarkers of cardiovascular risk than does cigarette smoking.