bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oxygen dependence of respiration in rat spinotrapezius muscle contracting at 0.5–8 twitches per second
Authors: Golub Aleksander S. , Dodhy Sami C. , Pittman Roland N. 
Published: March 2018

The oxygen dependence of respiration was obtained in situ in microscopic regions of rat spinotrapezius muscle for different levels of metabolic activity produced by electrical stimulation at rates from 0.5 to 8 Hz. The rate of O2consumption (V̇o2) was measured with phosphorescence quenching microscopy (PQM) as the rate of O2disappearance in a muscle with rapid flow arrest. The phosphorescent oxygen probe was loaded into the interstitial space of the muscle to give O2tension (Po2) in the interstitium. A set of sigmoid curves relating the Po2dependence of V̇o2was obtained with a Po2-dependent region below a characteristic Po2(~30 mmHg) and a Po2-independent region above this Po2. The V̇o2(Po2) plots were fit by the Hill equation containing O2demand (rest to 8 Hz: 216 ± 26 to 636 ± 77 nl O2/cm3s) and the Po2value corresponding to O2demand/2 (rest to 8 Hz: 22 ± 4 to 11 ± 1 mmHg). The initial Po2and V̇o2pairs of values measured at the moment of flow arrest formed a straight line, determining the rate of oxygen supply. This line had a negative slope, equal to the oxygen conductance for the O2supply chain. For each level of tissue blood flow the set of possible values of Po2and V̇o2consists of the intersection points between this O2supply line and the set of V̇o2curves. An electrical analogy for the intraorgan O2supply and consumption is an inverting transistor amplifier, which allows the use of graphic analysis methods for prediction of the behavior of the oxygen processing system in organs.NEW & NOTEWORTHY The sigmoidal shape of curves describing oxygen dependence of muscle respiration varies from basal to maximal workload and characterizes the oxidative metabolism of muscle. The rate of O2supply depends on extracellular O2tension and is determined by the overall oxygen conductance in the muscle. The dynamics of oxygen consumption is determined by the supply line that intersects the oxygen demand curves. An electrical analogy for the oxygen supply/consumption system is an inverting transistor amplifier.
HER2 Deregulation in Lung Cancer: Right Time to Adopt an Orphan?
Authors: Cappuzzo Federico , Landi Lorenza 
Published: March 2018

Abstract
HER2-deregulated non–small cell lung cancer is an orphan of any specific therapy, probably because of lack of both accurate patient selection and effective drugs. Recent evidence suggests that osimertinib could be effective in HER2-amplified or mutated lung cancer as a single agent or in combination. Clin Cancer Res; 24(11); 2470–2. ©2018 AACR.
See related article by Liu et al., p. 2594
Targeted Doxorubicin-Loaded Bacterially Derived Nano-Cells for the Treatment of Neuroblastoma
Authors: Sagnella Sharon M. , Trieu Jennifer , Brahmbhatt Himanshu , MacDiarmid Jennifer A. , MacMillan Alex , Whan Renee M. , Fife Christopher M. , McCarroll Joshua A. , Gifford Andrew J. , Ziegler David S. , Kavallaris Maria 
Published: March 2018

Abstract
Advanced stage neuroblastoma is an aggressive disease with limited treatment options for patients with drug-resistant tumors. Targeted delivery of chemotherapy for pediatric cancers offers promise to improve treatment efficacy and reduce toxicity associated with systemic chemotherapy. The EnGeneIC Dream Vector (EDVTM) is a nanocell, which can package chemotherapeutic drugs and target tumors via attachment of bispecific proteins to the surface of the nanocell. Phase I trials in adults with refractory tumors have shown an acceptable safety profile. Herein we investigated the activity of EGFR-targeted and doxorubicin-loaded EDVTM (EGFREDVTMDox) for the treatment of neuroblastoma. Two independent neuroblastoma cell lines with variable expression of EGFR protein [SK-N-BE(2), high; SH-SY-5Y, low] were used. EGFREDVTMDox induced apoptosis in these cells compared to control, doxorubicin, or non-doxorubicin loaded EGFREDVTM. In three-dimensional tumor spheroids, imaging and fluorescence life-time microscopy revealed that EGFREDVTMDox had a marked enhancement of doxorubicin penetration compared to doxorubicin alone, and improved penetration compared to non-EGFR-targeted EDVTMDox, with enhanced spheroid penetration leading to increased apoptosis. In two independent orthotopic human neuroblastoma xenograft models, short-term studies (28 days) of tumor-bearing mice led to a significant decrease in tumor size in EGFREDVTMDox-treated animals compared to control, doxorubicin, or non-EGFR EDVTMDox. There was increased TUNEL staining of tumors at day 28 compared to control, doxorubicin, or non-EGFR EDVTMDox. Moreover, overall survival was increased in neuroblastoma mice treated with EGFREDVTMDox (P &lt; 0007) compared to control. Drug-loaded bispecific-antibody targeted EDVsTM offer a highly promising approach for the treatment of aggressive pediatric malignancies such as neuroblastoma. Mol Cancer Ther; 17(5); 1012–23. ©2018 AACR.
Designing Late-Stage Randomized Clinical Trials with Cancer Immunotherapy: Can We Make It Simpler?
Authors: Chen Tai-Tsang 
Published: March 2018

AbstractThe knowledge we have accumulated over the past few years in the field of cancer immunotherapy has prompted the research community to challenge the status quo of trial design and endpoint selection across all drug development phases. For the design of randomized phase III studies using overall survival (OS) as the primary endpoint in particular, the paradigm has shifted from the conventional approach based on a proportional hazards model to those that account for the unique survival kinetics observed in immuno-oncology trials, such as long-term survival and delayed clinical effect. These new approaches usually require complex modeling or simulations, as well as assumptions about the length of delay in clinical effect and the long-term survival rate, making the process of implementing these new designs challenging. Here, a late-stage randomized clinical trial design is proposed based on milestone survival to simplify the process of sample size determination while keeping OS as the primary endpoint. The new design also allows assessment in milestone survival and is unaffected by the uncertainty of the survival kinetics demonstrated by cancer immunotherapies. Cancer Immunol Res; 6(3); 250–4. ©2018 AACR.
Inhibition of Local Macrophage Growth Ameliorates Focal Inflammation and Suppresses Atherosclerosis
Authors: Yamada Sarie , Senokuchi Takafumi , Matsumura Takeshi , Morita Yutaro , Ishii Norio , Fukuda Kazuki , Murakami-Nishida Saiko , Nishida Shuhei , Kawasaki Shuji , Motoshima Hiroyuki , Furukawa Noboru , Komohara Yoshihiro , Fujiwara Yukio , Koga Tomoaki , Yamagata Kazuya , Takeya Motohiro , Araki Eiichi 
Published: March 2018

Objective—
Macrophages play a central role in various stages of atherosclerotic plaque formation and progression. The local macrophages reportedly proliferate during atherosclerosis, but the pathophysiological significance of macrophage proliferation in this context remains unclear. Here, we investigated the involvement of local macrophage proliferation during atherosclerosis formation and progression using transgenic mice, in which macrophage proliferation was specifically suppressed.

Approach and Results—

Inhibition of macrophage proliferation was achieved by inducing the expression of cyclin-dependent kinase inhibitor 1B, also known as p27
kip
, under the regulation of a scavenger receptor promoter/enhancer. The macrophage-specific human p27
kip
Tg mice were subsequently crossed with apolipoprotein E–deficient mice for the atherosclerotic plaque study. Results showed that a reduced number of local macrophages resulted in marked suppression of atherosclerotic plaque formation and inflammatory response in the plaque. Moreover, fewer local macrophages in macrophage-specific human p27
kip
Tg mice helped stabilize the plaque, as evidenced by a reduced necrotic core area, increased collagenous extracellular matrix, and thickened fibrous cap.

Conclusions—
These results provide direct evidence of the involvement of local macrophage proliferation in formation and progression of atherosclerotic plaques and plaque stability. Thus, control of macrophage proliferation might represent a therapeutic target for treating atherosclerotic diseases.
New species of the subfamily Braconinae (Hymenoptera: Braconidae) from the Russian Far East
Authors: SAMARTSEV KONSTANTIN G. 
Published: March 2018

Four new species from the Russian Far East, Bracon kasparyani sp. nov., B. kotenkoi sp. nov., B. santachezae sp. nov. and Uncobracon belokobylskii sp. nov., are described and short keys for their identification are presented.
Multidecadal Changes of Upper-Ocean Thermal Conditions in the Tropical Northwest Pacific Ocean versus South China Sea during 1960–2015
Authors: Chiang Tzu-Ling , Hsin Yi-Chia , Wu Chau-Ron 
Published: March 2018

Abstract
By analyzing the upper-ocean properties of observation-based hydrographic data and validated oceanic reanalysis products, this study presents multidecadal changes of oceanic surface and subsurface thermal conditions in the tropical northwest Pacific Ocean (TNWP) and South China Sea (SCS) during 1960–2015. The analysis reveals that a transition of a 30-yr trend took place in 1980s during the analyzed period for both the surface and subsurface environment. Generally, the warming trend of sea surface temperature (SST) in the TNWP has a similar multidecadal change to that in the SCS. However, a huge accumulating rate of upper-ocean heat content above the 26°C isotherm (UOHC26) showed up in the TNWP (about 3 times compared to that in the SCS) in the last 30 years. In the TNWP, the southward shift of the North Equatorial Current on the multidecadal time scale induces the vertical displacement of isotherms, leading to a strong subsurface warming around the top of the thermocline. Secondarily, the Pacific decadal oscillation (PDO)-related SST regulates the thermal structure in the mixed layer. The multidecadal UOHC26 in the SCS is mainly attributed to the PDO-related SST and further modulated by the isothermal variability caused by the change of basin-scale SCS circulation.
An Ensemble Covariance Framework for Quantifying Forced Climate Variability and Its Time of Emergence
Authors: Yettella Vineel , Weiss Jeffrey B. , Kay Jennifer E. , Pendergrass Angeline G. 
Published: March 2018

Climate variability and its response to increasing greenhouse gases are important considerations for impacts and adaptation. Modeling studies commonly assess projected changes in variability in terms of changes in the variance of climate variables. Despite the distant and impactful covariations that climate variables can exhibit, the covariance response has received much less attention. Here, a novel ensemble framework is developed that facilitates a unified assessment of the response of the regional variances and covariances of a climate variable to imposed external forcings and their time of emergence from an unforced climate state. Illustrating the framework, the response of variability and covariability of land and ocean temperatures is assessed in the Community Earth System Model Large Ensemble under historical and RCP8.5 forcing. The results reveal that land temperature variance emerges from its preindustrial state in the 1950s and, by the end of the twenty-first century, grows to 1.5 times its preindustrial level. Demonstrating the importance of covariances for variability projections, the covariance between land and ocean temperature is considerably enhanced by 2100, reaching 1.4 times its preindustrial estimate. The framework is also applied to assess changes in monthly temperature variability associated with the Arctic region and the Northern Hemisphere midlatitudes. Consistent with previous studies and coinciding with sea ice loss, Arctic temperature variance decreases in most months, emerging from its preindustrial state in the late twentieth century. Overall, these results demonstrate the utility of the framework in enabling a comprehensive assessment of variability and its response to external climate forcings.
Dependence of Tropical Cyclone Intensification Rate on Sea Surface Temperature, Storm Intensity, and Size in the Western North Pacific
Authors: Xu Jing , Wang Yuqing 
Published: March 2018

Abstract
This study extends the statistical analysis on the dependence of tropical cyclone (TC) intensification rate (IR) on sea surface temperature (SST), storm initial intensity (maximum sustained surface wind speed Vmax), and storm size, in terms of the radius of maximum wind (RMW), the radius of 34-kt (AR34; 1 kt = 0.51 m s−1) wind, and the outer-core wind skirt parameter DR34 (= AR34 − RMW), for North Atlantic TCs to western North Pacific (WNP) TCs during 1982–2015. Results show that the relationship between the TC maximum potential intensification rate (MPIR) and SST also exists in the WNP. TC IR depends strongly on TC intensity and structure, consistent with the findings for North Atlantic TCs. TC IR is positively (negatively) correlated with storm intensity when Vmax is below (above) 70 kt and negatively correlated with the RMW. Rapid intensification (RI) occurs only in a relatively narrow range of parameter space in storm intensity and both inner- and outer-core sizes, with the highest IR appearing for Vmax = 70 kt, RMW ≦ 40 km, AR34 = 150 km, and DR34 = 100 km. The highest frequency of occurrence of intensifying TCs occurs for Vmax ~ 40–60 kt, RMW ~ 20–60 km, AR34 = 200 km, and DR34 = 120 km. Overall, these values are very similar to those for TCs in the North Atlantic. These results suggest the need for the realistic initialization of TC structure in numerical models and the inclusion of size parameters in statistical TC intensity prediction schemes.
Contemporary challenges for specialist nursing in interstitial lung disease
Authors: Russell Anne Marie , Olive Sandra , Lines Sarah , Murphy Anna , Hocking Julie , Newell Karen , Morris Helen , Harris Emma , Dixon Catherine , Agnew Sarah , Burge Geraldine 
Published: March 2018

The role of clinical nurse specialists (CNSs) in interstitial lung disease (ILD) is evolving in response to clinical guidelines and the growth of clinical research. The role is well established in the UK, although more ILD posts are needed to ensure supply meets clinical demand. This phenomenon is also happening across Europe. An appreciation of the similarities and differences between CNS and advanced nurse practitioners is important given the challenges in defining, developing and supporting this nursing specialisation. Globally, different models exist. In some countries charitable organisations take a leading role in supporting patients. Many European centres look to the National Institute for Health and Care Excellence guidelines and quality standards as a template to develop and evaluate the role of the ILD CNS. We present a UK perspective in the context of a government subsidised healthcare system to promote professional discussion and debate regarding the future of nursing practice in the ILD specialty.Key pointsILDs are often complex and associated with significant mortality, morbidity and co-morbid conditions that require a technical healthcare skill setThere is worldwide shortage of nurses, low retention rates and retirement of many skilled nursesCollaboration across the ILD interdisciplinary community is needed to safeguard the future of our professions and high-quality patient careThe ILD interdisciplinary and nurse network has identified key priorities to help secure the future of the ILD clinical and academic nurse specialismEducational aimsTo explain the similarities and differences between clinical nurse specialists (CNSs) and advanced nurse practitioners (ANPs) in the context of ILD specialismTo review contemporary nursing specialism in the UK’s government subsidised healthcare systemTo stimulate discussion and debate across the European/international respiratory community regarding the clinical and academic development of the ILD CNSTo identify key priorities that will support collaboration across the ILD interdisciplinary workforce in clinical practice and research
Clinical and histological features of second breast cancers following radiotherapy for childhood and young adult malignancy
Authors: Demoor-goldschmidt Charlotte , Supiot Stéphane , Mahé Marc-André , Oberlin Odile , Allodji Rodrigue , Haddy Nadia , Helfre Sylvie , Vigneron Céline , Brillaud-Meflah Victoire , Bernier Valérie , Laprie Anne , Ducassou Anne , Claude Line , Diallo Ibrahim , de Vathaire Florent 
Published: March 2018

Objective:
The purpose of this study was to determine the characteristics of early second breast cancer (SBC) among survivors of childhood and young adult malignancy treated with irradiation.

Methods:
We conducted a multicenter retrospective study of women who presented with breast cancer aged 50 years or younger in nine French centers.

Results:
121 patients and 141 SBC were analyzed (invasive = 130; non-invasive = 11). The mean age at first cancer diagnosis was 15 years and at initial SBC diagnosis was 38 years. Bilateral disease before the age of 51 years was diagnosed in 16% of the females. The majority of SBC were invasive carcinomas (92%). Among the invasive carcinomas, 39% had a histoprognostic score of III, 3.1% overexpressed HER2 and 29% were triple negative. The proportion of triple negative phenotype SBC was higher in patients older at first cancer diagnosis [RR = 1.2, 95% CI (1.1–1.3)]. 94% of triple negative SBCs developed in breast tissue which had received &gt;20 Gy.

Conclusion:
We found a high proportion of aggressive SBC following thoracic radiotherapy in childhood or early adulthood.

Advances in knowledge:
SBC screening is recommended by scientific societies for these child/young–adulthood cancer survivors in the same way as the one for high risk women because of constitutional mutations. Our results support these recommendations, not only because of a similar cumulative risk, but also because of the aggressive histological characteristics.
Safe transfer of simulation-based intubation skills to patients in cardiac arrest
Authors: Nørregaard Annette , Madsen Jacob , Leutscher Peter , Lambert Per 
Published: March 2018

Background: Studies investigating the transfer of endotracheal intubation skills from simulation training to out-of-hospital patient scenarios are limited. Aims: The aim was to evaluate the outcome of endotracheal intubation simulation training among paramedics and the safe transfer of skills to out-of-hospital cardiac arrest (OHCA) patients. Methods: Paramedics participated in a 1-day simulation training course including five Airtraq endotracheal intubation attempts using three different types of mannequins (n=15 attempts). Performance and outcome of transfer of intubation skills to patients were monitored for the next 35 months. European Resuscitation Council international advanced cardiopulmonary resuscitation guidelines ( Nolan et al, 2005 ) were followed to ensure patient safety. Findings: Endotracheal intubation was attempted in a total of 417 patients with OHCA by 51 (96%) of the 53 participating paramedics. In 366 (88%) patients, intubation was successfully performed in the first or second attempt. Aspiration, airway secretion, a high modified Cormack Lehane score and insecure verification of tube placement were the most common reasons for failed intubation. Conclusion: Endotracheal intubation with Airtraq in adult patients with OHCA can be performed safely by paramedics after receiving a 1-day simulation-based training course.
Exact Analytical Durometer Hardness Scale Interconversion
Authors: Gilbert P. H. , Giacomin A. J. 
Published: March 2018

Abstract
Previous work has related Young’s modulus to durometer hardness for any standardized scale. In this paper, we build on this work to solve explicitly and exactly for the hardness in any one standardized durometer hardness scale as a function of the hardness in any other target scale. We find that when the target scale is for a flat indenter, the conversion is algebraic and straightforward. However, when the target scale is for an indenter that is not flat (conical or hemispherical), the exact explicit analytical solution requires a power series inversion, said series involving beta functions and solutions to a set of integer equations. We complete our analysis with two worked examples illustrating the use of our interconversion equations and charts.
A Nonsense Variant in the ACADVL Gene in German Hunting Terriers with Exercise Induced Metabolic Myopathy
Authors: Lepori Vincent , Mühlhause Franziska , Sewell Adrian C , Jagannathan Vidhya , Janzen Nils , Rosati Marco , Alves de Sousa Filipe Miguel Maximiano , Tschopp Aurélie , Schüpbach Gertraud , Matiasek Kaspar , Tipold Andrea , Leeb Tosso , Kornberg Marion 
Published: March 2018

Abstract
Several enzymes are involved in fatty acid oxidation, which is a key process in mitochondrial energy production. Inherited defects affecting any step of fatty acid oxidation can result in clinical disease. We present here an extended family of German Hunting Terriers with 10 dogs affected by clinical signs of exercise induced weakness, muscle pain, and suspected rhabdomyolysis. The combination of clinical signs, muscle histopathology and acylcarnitine analysis with an elevated tetradecenoylcarnitine (C14:1) peak suggested a possible diagnosis of acyl-CoA dehydrogenase very long chain deficiency (ACADVLD). Whole genome sequence analysis of one affected dog and 191 controls revealed a nonsense variant in the ACADVL gene encoding acyl-CoA dehydrogenase very long chain, c.1728C&gt;A or p.(Tyr576*). The variant showed perfect association with the phenotype in the 10 affected and more than 500 control dogs of various breeds. Pathogenic variants in the ACADVL gene have been reported in humans with similar myopathic phenotypes. We therefore considered the detected variant to be the most likely candidate causative variant for the observed exercise induced myopathy. To our knowledge, this is the first description of this disease in dogs, which we propose to name exercise induced metabolic myopathy (EIMM), and the identification of the first canine pathogenic ACADVL variant. Our findings provide a large animal model for a known human disease and will enable genetic testing to avoid the unintentional breeding of affected offspring.