bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined Cellular and Biochemical Profiling to Identify Predictive Drug Response Biomarkers for Kinase Inhibitors Approved for Clinical Use between 2013 and 2017
Authors: Uitdehaag Joost C.M. , Kooijman Jeffrey J. , de Roos Jeroen A.D.M. , Prinsen Martine B.W. , Dylus Jelle , Willemsen-Seegers Nicole , Kawase Yusuke , Sawa Masaaki , de Man Jos , van Gerwen Suzanne J.C. , Buijsman Rogier C. , Zaman Guido J.R. 
Published: October 2018

Abstract
Kinase inhibitors form the largest class of precision medicine. From 2013 to 2017, 17 have been approved, with 8 different mechanisms. We present a comprehensive profiling study of all 17 inhibitors on a biochemical assay panel of 280 kinases and proliferation assays of 108 cancer cell lines. Drug responses of the cell lines were related to the presence of frequently recurring point mutations, insertions, deletions, and amplifications in 15 well-known oncogenes and tumor-suppressor genes. In addition, drug responses were correlated with basal gene expression levels with a focus on 383 clinically actionable genes. Cell lines harboring actionable mutations defined in the FDA labels, such as mutant BRAF(V600E) for cobimetinib, or ALK gene translocation for ALK inhibitors, are generally 10 times more sensitive compared with wild-type cell lines. This sensitivity window is more narrow for markers that failed to meet endpoints in clinical trials, for instance CDKN2A loss for CDK4/6 inhibitors (2.7-fold) and KRAS mutation for cobimetinib (2.3-fold). Our data underscore the rationale of a number of recently opened clinical trials, such as ibrutinib in ERBB2- or ERBB4-expressing cancers. We propose and validate new response biomarkers, such as mutation in FBXW7 or SMAD4 for EGFR and HER2 inhibitors, ETV4 and ETV5 expression for MEK inhibitors, and JAK3 expression for ALK inhibitors. Potentially, these new markers could be combined to improve response rates. This comprehensive overview of biochemical and cellular selectivities of approved kinase inhibitor drugs provides a rich resource for drug repurposing, basket trial design, and basic cancer research.
Outcomes, Costs, and 30-Day Readmissions After Catheter Ablation of Myocardial Infarct–Associated Ventricular Tachycardia in the Real World
Authors: Cheung Jim W. , Yeo Ilhwan , Ip James E. , Thomas George , Liu Christopher F. , Markowitz Steven M. , Lerman Bruce B. , Kim Luke K. 
Published: October 2018

Background:
Patients undergoing catheter ablation of myocardial infarction–associated ventricular tachycardia (VT) have significant comorbidities that can increase the risks of adverse outcomes. The rates of readmissions after VT ablation are unknown. We sought to examine in-hospital outcomes, costs, and 30-day readmissions after catheter ablation of myocardial infarction–associated VT.

Methods:

Using the Nationwide Readmissions Database, we evaluated 4109 admissions for catheter ablation of myocardial infarction–associated VT occurring between 2010 and 2015. On the basis of
International Classification of Diseases, Ninth Revision, Clinical Modification
and Clinical Classification Software codes, we identified comorbidities, procedural complications, 30-day readmissions, and costs associated with VT ablation.

Results:
The index admission in-hospital mortality rate and procedural complication rate after VT ablation were 2.7% and 11.5%, respectively. Independent predictors of mortality included pulmonary hypertension, lung disease, obesity, and coagulopathy. Following discharge after VT ablation, the 30-day readmission rate was 19.2% with a median time to readmission of 10.0 days (IQR, 3.8–17.6 days) and an in-hospital mortality rate of 2.9%. Cardiac causes accounted for 74% of readmissions, with VT and congestive heart failure constituting 41% and 14% of all readmissions, respectively. Pulmonary hypertension, congestive heart failure, smoking, chronic pulmonary disease, and prolonged index hospitalization were significant independent predictors of 30-day readmission. After adjustment, 30-day readmissions were associated with a 38.9% increase in cumulative hospitalization costs.

Conclusions:
Thirty-day readmissions after catheter ablation of VT occur in nearly 1 out of 5 cases, with the majority of readmissions being caused by recurrent VT or congestive heart failure. Baseline comorbidities are significant predictors of procedural mortality, complications, and readmissions. Strategies to reduce recurrent VT postablation by improving procedural success, optimizing postablation heart failure treatment, and ensuring close postdischarge follow-up may help reduce readmissions and healthcare costs.
High‐Intensity Versus Non‐High‐Intensity Statins in Patients Achieving Low‐Density Lipoprotein Cholesterol Goal After Percutaneous Coronary Intervention
Authors: Kim Juwon , Park Kyu Tae , Jang Mi Ja , Park Taek Kyu , Lee Joo Myung , Yang Jeong Hoon , Song Young Bin , Choi Seung‐Hyuk , Gwon Hyeon‐Cheol , Lee Sang‐Hoon , Hong Kyung Pyo , Hahn Joo‐Yong 
Published: October 2018

Background

Whether use of high‐intensity statins is more important than achieving low‐density lipoprotein cholesterol (
LDL
‐C) target remains controversial in patients with coronary artery disease. We sought to investigate the association between statin intensity and long‐term clinical outcomes in patients achieving treatment target for
LDL
‐C after percutaneous coronary intervention.

Methods and Results

Between February 2003 and December 2014, 1746 patients who underwent percutaneous coronary intervention and achieved treatment target for
LDL
‐C (<70 mg/dL or >50% reduction from baseline level) were studied. We classified patients into 2 groups according to an intensity of statin prescribed after index percutaneous coronary intervention: high‐intensity statin group (atorvastatin 40 or 80 mg, and rosuvastatin 20 mg, 372 patients) and non‐high‐intensity statin group (the other statin treatment, 1374 patients). The primary outcome was a composite of cardiac death, myocardial infarction, or stroke. Difference in time‐averaged
LDL
‐C during follow‐up was significant, but small, between the high‐intensity statin group and non‐high‐intensity statin group (59±13 versus 61±12 mg/dL;
P
=0.04). At 5 years, patients receiving high‐intensity statins had a significantly lower incidence of the primary outcome than those treated with non‐high‐intensity statins (4.1% versus 9.9%; hazard ratio, 0.42; 95% confidence interval, 0.23–0.79;
P
<0.01). Results were consistent after propensity‐score matching (4.2% versus 11.2%; hazard ratio, 0.36; 95% confidence interval, 0.19–0.69;
P
<0.01) and across various subgroups.

Conclusions

Among patients achieving treatment target for
LDL
‐C after percutaneous coronary intervention, high‐intensity statins were associated with a lower risk of major adverse cardiovascular events than non‐high‐intensity statins despite a small difference in achieved
LDL
‐C level.
Quality of Care and Outcomes for Patients With Stroke in the United States Admitted During the International Stroke Conference
Authors: Messé Steven R. , Mullen Michael T. , Cox Margueritte , Fonarow Gregg C. , Smith Eric E. , Saver Jeffrey L. , Reeves Mathew J. , Bhatt Deepak L. , Matsouaka Roland , Schwamm Lee H. 
Published: October 2018

Background

Patients presenting to hospitals during non–weekday hours experience worse outcomes, often attributed to reduced staffing. The American Heart Association International Stroke Conference (
ISC
) is well attended by stroke clinicians. We sought to determine whether patients with acute ischemic stroke (
AIS
) admitted during the
ISC
receive less guideline‐adherent care and experience worse outcomes.

Methods and Results

We performed a retrospective cohort study of
US
hospitals participating in Get With The Guidelines–Stroke and assessed use of intravenous tissue plasminogen activator, other quality measures, and outcomes for patients with AIS admitted during the
ISC
compared with those admitted the weeks before and after the conference. A total of 69 738 patients with
AIS
were included: mean age, 72 years; 52% women; 29% nonwhite. There was no difference between the average weekly number of
AIS
cases admitted during
ISC
weeks versus non‐
ISC
weeks (1984 versus 1997;
P
=0.95). Patient and hospital characteristics were similar between
ISC
and non‐
ISC
time periods. There were no significant differences in 14 quality metrics and 5 clinical outcomes between patients with AIS treated during the
ISC
versus non‐
ISC
weeks. Patients with AIS who presented within 2 hours of onset had no difference in the likelihood of receiving intravenous tissue plasminogen activator within 3 hours (adjusted odds ratio, 0.89; 95% confidence interval, 0.77–1.03;
P
=0.13) or the likelihood of receiving intravenous tissue plasminogen activator within 60 minutes of arrival (adjusted odds ratio, 0.92; 95% confidence interval, 0.83–1.02;
P
=0.13).

Conclusions

Patients with acute stroke admitted to Get With The Guidelines–Stroke hospitals during
ISC
received the same quality care and had similar outcomes as patients admitted at other times.
Nonhuman Animal Behavioral Phenomena Are Central to the Emerging Concept of Intangible Natural Heritage
Authors: Robischon Marcel 
Published: October 2018

AbstractIntangible natural heritage is a concept that has been addressed in several publications and that offers a new and expanded view onto world heritage conservation. However, the difference from intangible cultural heritage has not been clearly defined. One distinction in the categories of world heritage that are established in international conventions appears where “the intangible” is not created by humans but by a nonhuman animal. Living organisms sustain human life materially and provide inspiration to humans, both in their material form and by displaying behaviors, or via observable, yet not tangible, dynamic phenomena and processes. This includes migration patterns, aggregations, vocalizations or the formation of symbiotic and mutualistic inter-species relationships. Given the non-material character of these elements, their transmission by nonhuman living beings, and their importance to human culture, it is proposed that such phenomena are considered as intangible natural heritagesensu strictoin the discourse of world heritage.
Standard Terms Contracts: The Approaches of Qatari Civil Law and UNIDROIT Principles 2016. A Comparative Study
Authors: Mahasneh Nisreen 
Published: October 2018

Abstract
This study compares the approach that Qatari Civil Law No. 22/2004 (QCL) takes to standard terms with that taken by the UNIDROIT Principles of International Commercial Contracts 2016. The main difference between QCL and the UNIDROIT Principles, is that the QCL relates standard terms contracts with adhesion contracts. The latter are only concerned with strategic goods and services that are monopolized by the supplier. Another difference is the remedy; under the QCL, the judge has the authority not only to exempt the adhering party from the oppressive standard term, but to also amend that term. However, under the UNIDROIT Principles, surprising terms are invalid. The study recommends that the Qatari legislator remove the connection in the QCL between standard terms contracts and adhesion contracts, and limit judges’ authority to exempting disadvantaged parties from oppressive terms.
On the Time Evolution of Limited-Area Ensemble Variance: Case Studies with the Convection-Permitting Ensemble COSMO-E
Authors: Klasa Christina , Arpagaus Marco , Walser André , Wernli Heini 
Published: October 2018

Abstract
Dynamical processes determining the time evolution of difference kinetic energy (DKE) in a limited-area domain are investigated with the convection-permitting ensemble model COSMO-E for a forecasting period of 4 days. DKE is quantified by means of ensemble variance of the irrotational and nondivergent horizontal wind. For three case studies characterized by contrasting predictability levels of precipitation, it is shown that DKE of the irrotational wind strongly increases during periods of solar-forced moist convective activity and decreases when the latter ceases. The response of DKE of the nondivergent wind is also clearly related to the convective activity, but delayed by a few hours, pointing to interactions between both wind components. Apart from the impact of moist convection, DKE of the nondivergent wind is primarily governed by large-scale advection, imposed at the lateral domain boundaries of the limited-area ensemble. This forcing may also sustain or increase DKE of the irrotational wind when moist convection is absent. Consequently, the large-scale flow and diurnal solar forcing, associated with higher spatiotemporal predictability, determines the overall evolution of the limited-area ensemble variance of the horizontal wind, which increases in the presence of moist convective activity or strong synoptic-scale forcing, and stagnates or decreases otherwise, rendering forecasts of convection-permitting ensembles valuable beyond the very short forecast range.
Research on the mechanism of the modified ring-spinning system using a dynamic twist-resistant device and its yarn quality
Authors: Shao Ruiqi , Cheng Longdi , Yu Yanping , Xu Jianxin , Wu Jianming 
Published: October 2018

The spinning triangle is a critical area in the ring-spinning process; the geometry of the spinning triangle influences the distribution of the fiber tension, and affects the qualities of the spun yarn. In this paper, a kind of dynamic twist-resistant device that can affect the geometry of the spinning triangle is employed for improving the conventional ring-spinning system.  The yarn twists between the front roller nip and dynamic twist-resistant device were captured in the spinning process using a high-speed camera. Comparing yarn twists of the two types of yarn, the modified yarns have a lower twist angle, indicating that the device can produce resistant torque. Particle Flow Code software was used to simulate the acts of the device on the yarn, and the results verified the existence of resistant torque. The resistant torque on the yarn affects the geometry of the spinning triangle and the distribution of fiber tension. In addition, 19.4 and 14.5 tex cotton yarns with three different twists, 700, 800 and 900 tpm, were produced by the modified and conventional ring spinning. The comparative study revealed that the modified yarns have a better performance in terms of yarn strength and hairiness, and show no significant difference in terms of the yarn evenness when compared with the conventional yarns at the same twist level. The mechanism of the effect of the dynamic twist-resistant device on yarn qualities is discussed by analyzing the distribution of fiber tension.
Executive function deficit in betel-quid-dependent chewers: Mediating role of prefrontal cortical thickness
Authors: Zhu Xueling , Liu Shaohui , Liao Weihua , Kong Lingyu , Jiang Canhua , Yuan Fulai 
Published: October 2018

Background: Betel quid is the fourth most popular psychoactive agent worldwide. Neuroimaging studies have suggested betel-quid dependence is accompanied by abnormality in brain structure and function. However, the neural correlates of executive function deficit and prefrontal cortical thickness associated with betel-quid chewing still remain unclear. Objective: The present study aimed to examine the relationship between executive function deficit and prefrontal cortical thickness in chronic betel-quid chewers. Methods: Twenty-three betel-quid-dependent chewers and 26 healthy controls were recruited to participate in this study. Executive function was tested using three tasks. Cortical thickness analysis was analyzed with the FreeSurfer software package. Results: Behavioral results suggested a profound deficit of executive function in betel-quid-dependent chewers. Cortical thickness analysis revealed thinner cortex in the bilateral dorsolateral prefrontal cortex in betel-quid-dependent chewers. Further analysis suggested that cortical thickness of the bilateral dorsolateral prefrontal cortex mediated the correlation of betel-quid chewing and executive function. Conclusions: These results suggest the important role of executive function and cortical thickness of the dorsolateral prefrontal cortex with betel-quid chewing. Our findings provide evidence that executive function deficit may be mediated by the cortical thickness of the dorsolateral prefrontal cortex. These results could potentially help us develop novel ways to diagnose and prevent betel-quid dependence.
Localization of radio-recurrence within the prostate: anti-3-18F-FACBC PET/CT compared with multiparametric MRI using histopathology as reference standard
Authors: Tulipan Andreas Julius , Hole Knut Håkon , Vlatkovic Ljiljana , Revheim Mona-Elisabeth , Reijnen Jeroen Sebastiaan , Willoch Frode , Seierstad Therese , Lilleby Wolfgang 
Published: October 2018

Background Focal treatment of prostate cancer recurrence is emerging and increases the demand for precision in imaging; pure detection is no longer enough and accurate localization is needed. Purpose To investigate the ability of anti-1-amino-3-[18F]fluorocyclobutane-1-carboxylic acid (FACBC) PET/CT to localize radio-recurrences within the prostate, compared to multiparametric magnetic resonance imaging (mpMRI) and with histopathology as the reference standard. Material and Methods This prospective salvage focal brachytherapy protocol included 20 patients (mean age = 66 years; age range = 57–72 years) with biochemical recurrence after primary radiotherapy. All patients underwent mpMRI, FACBC PET/CT, prostate biopsies, and bone marrow aspiration. The mean time between mpMRI and FACBC PET/CT was 68 days (range = 5–147 days). Two radiologists and two nuclear medicine physicians independently interpreted MRI and PET. Based on schematic drawings, the quadrant (right, left, anterior, posterior) and the level (apex, mid, base) of tumor recurrence were compared and correlated to histopathology. Written informed consent was obtained from all patients. Results PET correctly localized the recurrence in 15 of 20 patients and MRI correctly localized 19 of 20 patients. MRI and PET were concordant for 14 of these 20 patients. There was perfect agreement between the MRI radiologists. Except for one case in which the lesion was only detected by one of the readers, there was also agreement between the nuclear medicine physicians. Conclusions FACBC PET/CT detected fewer histological verified radio-recurrences within the prostate than mpMRI. In accordance with previous studies, we found that the limitations of FACBC PET were small tumor amounts and uptake in hyperplastic benign tissue.
Impact of setup orientation on blend electrospinning of poly-ε-caprolactone-gelatin scaffolds for vascular tissue engineering
Authors: Suresh Sinduja , Gryshkov Oleksandr , Glasmacher Birgit 
Published: October 2018

Introduction: This article explores the effect of horizontal and vertical setups on blend electrospinning with two polymers having vastly different properties – poly-ε-caprolactone and gelatin, and subsequent effect of the resulting microstructure on viability of seeded cells. Methods: Poly-ε-caprolactone and gelatin of varying blend concentrations were electrospun in horizontal and vertical setup orientations. NIH 3T3 fibroblasts were seeded on these scaffolds to assess cell viability changes in accordance with change in microstructure. Results: Blend electrospinning yielded a heterogeneous microstructure in the vertical orientation beyond a critical concentration of gelatin, and a homogeneous microstructure in the horizontal orientation. Unblended poly-ε-caprolactone electrospinning showed no significant difference in fibre diameter or pore size in either orientation. Mechanical testing showed reduced elasticity when poly-ε-caprolactone is blended with gelatin but an overall increase in tensile strength in the vertically spun samples. Cells on vertically spun samples showed significantly higher viabilities by day 7. Discussion: The composite microstructure obtained in vertically spun poly-ε-caprolactone -gelatin blends has a positive effect on viability of seeded cells. Such scaffolds can be considered suitable candidates for cardiovascular tissue engineering where cell infiltration is crucial.
Relationship Between Near-Infrared Spectroscopy-Derived Cerebral Oxygenation and Delirium in Critically Ill Patients: A Systematic Review
Authors: Bendahan Nathaniel , Neal Oliver , Ross-White Amanda , Muscedere John , Boyd J. Gordon 
Published: October 2018

Background: A common neurological complication of critical illness is delirium, defined as an acute change in level of consciousness, with impaired attention and disorganized thinking. Patients with delirium have increased risk of long-term cognitive dysfunction and mortality. The cause is unknown, which limits our ability to design therapeutic interventions. In patients undergoing surgery, low regional cerebral oxygenation (rSO2), as measured by near-infrared spectroscopy (NIRS), is associated with postoperative neurological dysfunction (eg delirium and long-term cognitive impairment). However, the relationship between NIRS-derived rSO2 and neurological outcomes in critically ill patients is unclear. The objective of this study was to assess the utilization of NIRS-derived rSO2 in critically ill patients outside the operating theater. We aimed to examine the relationship between rSO2 and neurological outcomes as well as to report rSO2 values in this population. Methods: The following databases were searched from inception to August 14, 2017: Ovid MedLine, Embase, Cochrane Library, and Web of Science. Results: Of 1410 articles identified by the search strategy, 8 were ultimately selected for final review. Most (7 of 8) were published since 2014. These studies included a total of 213 patients primarily with shock or respiratory failure. A variety of devices were used to measure rSO2, including INVOS and FORESIGHT. The duration of recording varied from 5 minutes to 72 hours. Four of the 8 studies reported on neurological outcomes. In all 4 studies, rSO2 was lower in critically ill patients who were delirious compared to controls, but this was only statistically significant in 2 of the studies. The heterogeneity in devices and duration of recording precluded meta-analysis. Conclusions: There is limited literature describing rSO2 in critically ill patients outside the operating room. Although there may be a slight signal of an association between low rSO2 and delirium, more study is needed to explore this relationship.