bluuebunny/crossref_metadata_2025 huggingface dataset:
A Mixed‐methods Comparison of Participant and Observer Learner Roles in Simulation Education
Authors: Bullard Mark J. , Weekes Anthony J. , Cordle Randolph J. , Fox Sean M. , Wares Catherine M. , Heffner Alan C. , Howley Lisa D. , Navedo Deborah
Published: November 2018

Background

Traditional simulation‐based education prioritizes participation in simulated scenarios. The educational impact of observation in simulation‐based education compared with participation remains uncertain. Our objective was to compare the performances of observers and participants in a standardized simulation scenario.

Methods

We assessed learning differences between simulation‐based scenario participation and observation using a convergent, parallel, quasi‐experimental, mixed‐methods study of 15 participants and 15 observers (N = 30). Fifteen first‐year residents from six medical specialties were evaluated during a simulated scenario (cardiac arrest due to critical hyperkalemia). Evaluation included predefined critical actions and performance assessments. In the first exposure to the simulation scenario, participants and observers underwent a shared postevent debriefing with predetermined learning objectives. Three months later, a follow‐up assessment using the same case scenario evaluated all 30 learners as participants. Wilcoxon signed rank and Wilcoxon rank sum tests were used to compare participants and observers at 3‐month follow‐up. In addition, we used case study methodology to explore the nature of learning for participants and observers. Data were triangulated using direct observations, reflective field notes, and a focus group.

Results

Quantitative data analysis comparing the learners’ first and second exposure to the investigation scenario demonstrated participants’ time to calcium administration as the only statistically significant difference between participant and observer roles (316 seconds vs. 200 seconds, p = 0.0004). Qualitative analysis revealed that both participation and observation improved learning, debriefing was an important component to learning, and debriefing closed the learning gap between observers and participants.

Conclusions

Participants and observers had similar performances in simulation‐based learning in an isolated scenario of cardiac arrest due to hyperkalemia. Findings support current limited literature that observation should not be underestimated as an important opportunity to enhance simulation‐based education. When paired with postevent debriefing, scenario observers and participants may reap similar educational benefits.
Thalamic strokes that severely impair arousal extend into the brainstem
Authors: Hindman Joseph , Bowren Mark D. , Bruss Joel , Wright Brad , Geerling Joel C. , Boes Aaron D.
Published: November 2018

In this study, we evaluate the role of the thalamus in the neural circuitry of arousal. Level of consciousness within the first 12 hours of a thalamic stroke is assessed with lesion symptom mapping. Impaired arousal correlates with lesions in the paramedian posterior thalamus near the centromedian and parafascicular nuclei, posterior hypothalamus, and midbrain tegmentum. All patients with severely impaired arousal (coma, stupor) had lesion extension into the midbrain and/or pontine tegmentum, whereas purely thalamic lesions did not severely impair arousal. These results are consistent with growing evidence that pathways most critical for human arousal lie outside the thalamus. Ann Neurol 2018;84:926–930
Attributable risk of Alzheimer's dementia attributed to age‐related neuropathologies
Authors: Boyle Patricia A. , Yu Lei , Leurgans Sue E. , Wilson Robert S. , Brookmeyer Ron , Schneider Julie A. , Bennett David A.
Published: November 2018

Objective

The degree to which Alzheimer's versus other neuropathologies contribute to the risk of Alzheimer's dementia is unknown. We examined the risk of Alzheimer's dementia attributable to pathologic AD and 8 other neuropathologies.

Methods

Participants (n = 1,161) came from 2 clinical‐pathological studies of aging. Multivariable logistic regression models examined associations of 8 neuropathological indices with Alzheimer's dementia and quantified the percentage of cases attributable to each. Furthermore, because some dementia cases are not driven by common neuropathologies, we re‐estimated the attributable risks after empirically adjusting for such cases.

Results

Of 1,161 persons, 512 (44.1%) had Alzheimer's dementia at time of death. With the exception of microinfarcts, all neuropathological indices were independently associated with greater odds of Alzheimer's dementia. Two hundred ten (41.0%) Alzheimer's dementia cases were attributable to pathological AD. Separately, 8.9% were attributable to macroscopic infarcts, 10.8% to Lewy bodies, 5.2% to hippocampal sclerosis, 11.7% to transactive response DNA‐binding protein 43, 8.1% to cerebral amyloid angiopathy, 6.0% to atherosclerosis, and 5.2% to arteriolosclerosis. A total of 83.3% of cases were attributable to all 8 indices combined. However, after further adjustment for cases driven by other factors, a total of 67.5% of cases were attributable to all 8 neuropathologic indices combined.

Interpretation

Pathological AD accounts for a considerable percentage of Alzheimer's dementia cases, but multiple other neuropathologies also contribute. In total, just over two‐thirds of Alzheimer's dementia cases are attributable to common age‐related neuropathologies, suggesting that other disease and resilience factors are important. ANN NEUROL 2019;85:114–124.
Proepicardium: Current Understanding of its Structure, Induction, and Fate
Authors: Niderla‐BieliŃska Justyna , Jankowska‐Steifer Ewa , Flaht‐Zabost Aleksandra , Gula Grzegorz , Czarnowska Elżbieta , Ratajska Anna
Published: November 2018

The proepicardium (PE) is a transitory extracardiac embryonic structure which plays a crucial role in cardiac morphogenesis and delivers various cell lineages to the developing heart. The PE arises from the lateral plate mesoderm (LPM) and is present in all vertebrate species. During development, mesothelial cells of the PE reach the naked myocardium either as free‐floating aggregates in the form of vesicles or via a tissue bridge; subsequently, they attach to the myocardium and, finally, form the third layer of a mature heart—the epicardium. After undergoing epithelial‐to‐mesenchymal transition (EMT) some of the epicardial cells migrate into the myocardial wall and differentiate into fibroblasts, smooth muscle cells, and possibly other cell types. Despite many recent findings, the molecular pathways that control not only proepicardial induction and differentiation but also epicardial formation and epicardial cell fate are poorly understood. Knowledge about these events is essential because molecular mechanisms that occur during embryonic development have been shown to be reactivated in pathological conditions, for example, after myocardial infarction, during hypertensive heart disease or other cardiovascular diseases. Therefore, in this review we intended to summarize the current knowledge about PE formation and structure, as well as proepicardial cell fate in animals commonly used as models for studies on heart development. Anat Rec, 302:893–903, 2019. © 2018 Wiley Periodicals, Inc.
Bifurcation control of small‐world networks with delays VIA PID controller
Authors: Tao Binbin , Xiao Min , Jiang Guoping , Sun Qingshan
Published: November 2018

In this paper, the problem of bifurcation control for a small‐world network model with time delay is studied. We first put forward a Proportional‐Integral‐Derivative (PID) feedback scheme to control the Hopf bifurcation of the network. The time delay is selected as the bifurcation parameter. The conditions of the stability and Hopf bifurcation are given for the controlled network. By using the center manifold theorem and the normal form theory, the direction and stability of bifurcating periodic solutions are confirmed. The feasible region of the parameters of the controller is determined. It is found that the bifurcation dynamics of the small‐world network are optimized by adjusting the parameters of the PID controller. Finally, a numerical example verifies the effectiveness of the designed PID controller, and the relationships between the onset of the Hopf bifurcation and the control parameters are obtained.
A UFLC–MS/MS method for the simultaneous determination of eight bioactive constituents from red wine and dealcoholized red wine in rat plasma: Application to a comparative pharmacokinetic study
Authors: Bai Shuang , Li Pei , Liu Jing , Cui Can , Li Qing , Bi Kaishun
Published: November 2018

To explore whether alcohol has an effect on the pharmacokinetic behavior of phenolic acids, the main bioactive constituents in red wine, a highly sensitive and simple ultra‐fast liquid chromatography coupled with triple quadrupole mass spectrometry (UFLC–MS/MS) method was developed for simultaneous quantitation of eight phenolic acids in plasma samples. Plasma samples were extracted by liquid–liquid extraction and the chromatographic separation was achieved on a Zorbax SB‐C18 column within 7.0 min. Results of the validated method revealed that all of the calibration curves displayed good linear regression (r > 0.99). The intra‐ and inter‐day precisions of the analytes were <14.0% and accuracies ranged from −8.5 to 7.3%. The extraction recoveries of the analytes were from 71.2 to 110.2% and the matrix effects ranged from 86.2 to 105.5%. The stability of these compounds under various conditions satisfied the requirements of biological sample measurement. The method was successfully applied to a comparative pharmacokinetic study of phenolic acids in rat plasma. For gallic acid and gentisic acid, the parameters AUC0–t and AUC0–∞ increased remarkably (p < 0.05) after oral administration of red wine, which suggested that alcohol might enhance their absorption. This is the first report to compare the pharmacokinetic behavior of phenolic acids in red wine and dealcoholized red wine.
Catalytic characteristics of a sn‐1(3) regioselective lipase from Cordyceps militaris
Authors: Park Jun‐Young , Park Kyung‐Min , Yoo Yoonjung , Yu Hyunjong , Lee Chang Joo , Jung Ho‐Sup , Kim Keesung , Chang Pahn‐Shick
Published: November 2018

A total of 39 agricultural products were screened for natural sources of lipases with distinctive positional specificity. Based on this, Cordyceps militaris lipase (CML) was selected and subsequently purified by sequential chromatography involving anion‐exchange, hydrophobic‐interaction, and gel‐permeation columns. As a result of the overall purification procedure, a remarkable increase in the specific activity of the CML (4.733 U/mg protein) was achieved, with a yield of 2.47% (purification fold of 94.54). The purified CML has a monomeric structure with a molecular mass of approximately 62 kDa. It was further identified as a putative extracellular lipase from C. militaris by the partial sequence analysis using ESI‐Q‐TOF MS. In a kinetic study of the CML‐catalyzed hydrolysis, the values of Vmax, Km, and kcat were determined to be 4.86 μmol·min−1·mg−1, 0.07 mM, and 0.29 min−1, respectively. In particular, the relatively low Km value indicated that CML has a high affinity for its substrate. With regard to positional specificity, CML selectively cleaved triolein at the sn‐1 or 3 positions of glycerol backbone, releasing 1,2(2,3)‐diolein as the major products. Therefore, CML can be considered a distinctive biocatalyst with sn‐1(3) regioselectivity. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 35: e2744, 2019.
Method for isolation of pancreatic blood vessels, their culture and coculture with islets of langerhans
Authors: Lehmann Vivian , Andersen Parker L. , Damodaran Rajesh G. , Vermette Patrick
Published: November 2018

The only cure available for Type 1 diabetes involves the transplantation of islets of Langerhans isolated from donor organs. However, success rates are relatively low. Disconnection from vasculature upon isolation and insufficient rate of revascularization upon transplantation are thought to be a major cause, as islet survival and function depend on extensive vascularization. Research has thus turned toward the development of pretransplantation culture techniques to enhance revascularization of islets, so far with limited success. With the aim to develop a technique to enhance islet revascularization, this work proposes a method to isolate and culture pancreas‐derived blood vessels. Using a mild multistep digestion method, pancreatic blood vessels were retrieved from whole murine pancreata and cultured in collagen Type 1. After 8 days, 50% of tissue explants had formed anastomosed microvessels which extended up to 300 μm from the explant tissue and expressed endothelial cell marker CD31 but not ductal marker CK19. Cocultures with islets of Langerhans revealed survival of both tissues and insulin expression by islets up to 8 days post‐embedding. Microvessels were frequently found to encapsulate islets, however no islet penetration could be detected. This study reports for the first time the isolation and culture of pancreatic blood vessels. The methods and results presented in this work provide a novel explant culture model for angiogenesis and tissue engineering research with relevance to islet biology. It opens the door for in vivo validation of the potential of these pancreatic blood vessel explants to improve islet transplantation therapies. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 35: e2745, 2019.
Analyzing the suitability of a baffled orbitally shaken bioreactor for cells cultivation using the computational fluid dynamics approach
Authors: Zhu Likuan , Song Boyan , Wang Zhenlong
Published: November 2018

Orbitally shaken bioreactors (OSRs) is one of important bioreactors for mammalian cells cultivation in suspension, especially for the screening of valuable microorganisms and in basic bioprocess development experiments. However, the suitability of OSRs for cells culture in large scale is still under development. In this article, a new kind of OSRs with baffle structure was proposed and a three‐dimensional CFD model was established to analyze the influence of baffle structure on the flow field. Lower installation height of baffles was found suitable for improving the mixing efficiency. Compared to the unbaffled OSR, the baffled OSR could enhance the level of oxygen transfer largely but the oxygen transfer rate was independent on the baffle installation height. Moreover, as the baffle installation height increased, the energy transferred for liquid motion was decreased. Finally, the shear stress of the baffled OSRs proposed was gentle for mammalian cells growth. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 35: e2746, 2019
Learn how SAFETY Act can help protect athletics venues
Authors: McCarthy Claudine
Published: November 2018

ATLANTA — The stadiums and arenas where your school holds its sporting events and other large gatherings may be particularly vulnerable targets of potential terrorist activity, according to security experts. And that leaves your students, staff, and visitors exposed to significant safety risks and your school and department liable for hefty financial and punitive damages.
Effect of prior stroke on long‐term outcomes of percutaneous coronary interventions in Chinese patients: A large single‐center study
Authors: Xu Jing‐Jing , Song Ying , Jiang Ping , Gao Zhan , Li Jian‐Xin , Chen Jue , Yang Yue‐Jin , Gao Run‐Lin , Xu Bo , Yuan Jin‐Qing
Published: November 2018

Objectives

To evaluate the effect of prior stroke on long‐term outcomes in patients undergoing percutaneous coronary interventions (PCI).

Background

Patients with coronary heart disease (CHD) and prior stroke history have more serious clinical and angiographic conditions, which make the choice of treatment strategy complex.

Methods

A total of 10,724 consecutive patients who underwent PCI from January 2013 to December 2013 were enrolled. 2‐Year clinical outcomes between patients with prior stroke (n = 1150) and those with no prior stroke (n =9574) were compared.

Results

The proportion of patients with prior stroke was 10.72%. These patients had higher clinical risks (age, sex, and cardiovascular risk factors) and more extensive coronary disease (higher pre‐PCI and residual SYNTAX scores). During the 2‐year follow‐up, patients with prior stroke had a higher incidence of major adverse cardiac and cerebrovascular events (MACCE), all‐cause death, stent thrombosis and stroke than those without prior stroke (14.3% vs. 11.8%, p = 0.02; 2.3% vs. 1.1%, p < 0.01; 1.6% vs. 0.8%, p < 0.01; 3.3% vs. 1.1%, p < 0.01, respectively). Multivariable regression analyses identified a positive association between prior stroke and risk of stroke (HR = 2.07, 95%CI: 1.35–3.19, p < 0.01). Propensity score matched analyses (962 pairs) indicated that the only primary end point that differed in incidence between the groups was stroke and prior stroke was the only independent predictor of stroke (HR = 2.31, 95%CI: 1.20–4.45, p = 0.01).

Conclusions

Prior stroke history was the only predictor of risk of post‐PCI stroke. The noncerebrovascular adverse events were not increased after adjusted analyses of baseline characteristics and propensity analyses.
Die Polei‐Minze im Wandel der Zeiten
Authors: Prasse Agneta , Munzert Viola , José Elena , Zeller Klaus‐Peter , Siehl Hans‐Ullrich , Berger Stefan , Sicker D.
Published: November 2018

Das monocyclische Monoterpenketon (R)‐(+)‐Pulegon ist Hauptbestandteil des ätherischen Öls der Polei‐Minze (Flohkraut). Die Aufklärung der Struktur über die Etappen Summenformel, Konstitution und absolute Konfiguration zwischen 1891–1929 wird beschrieben. Früher wurde Polei‐Minze als Allheilmittel, Gewürz und gegen Flöhe eingesetzt. Heute wird von der Aufnahme des Inhaltsstoffs Pulegon abgeraten, denn Pulegon bildet im Metabolismus giftige Metaboliten. Das durch Wasserdampfdestillation gut zugängliche Poleiöl ist ein geschätzter Lieferant für (R)‐(+)‐Pulegon. Es stellt einen wertvollen enantiomerenreinen Baustein aus dem chiral pool der Natur für die Synthese chiraler Verbindungen dar. Alle Spektren des Pulegons eignen sich zum Üben spektroskopischer Interpretationen. Dieser Artikel setzt die Reihe zur Isolierung und Spektroskopie von Naturstoffen fort und beruht auf einer Bachelorarbeit. Er ergänzt die Kapitel des Buchs “Classics in Spectroscopy” von S. Berger und D. Sicker (Wiley‐VCH 2009).
Organizational model and reactions to alerts in remote monitoring of cardiac implantable electronic devices: A survey from the Home Monitoring Expert Alliance project
Authors: Zanotto Gabriele , D'Onofrio Antonio , Della Bella Paolo , Solimene Francesco , Pisanò Ennio C. , Iacopino Saverio , Dondina Cristina , Giacopelli Daniele , Gargaro Alessio , Ricci Renato P.
Published: November 2018

Background

This survey aimed to describe the organizational workflow of cardiac implantable electronic devices (CIEDs) remote monitoring (RM) service in ordinary practice.

Methods

A questionnaire was designed for our purpose and completed by 49 sites participating to the Italian Home Monitoring Expert Alliance.

Results

A dedicated organizational model for RM was set up for 86% of centers. The median RM team consisted of 2 (Interquartile range [IQR]: 1‐3) physicians and 1 (IQR: 0‐2) nurse. RM service was available in working hours and the median percentage of patients included was 100% (IQR: 10%‐100%) for implantable cardioverter‐defibrillator (ICD) and cardiac resynchronization therapy (CRT) recipients and 5% (IQR:0%‐30%) for pacemakers. In‐office follow‐up was performed every 12 and 6 months for pacemaker and ICD/CRT recipients, respectively. More than 90% of sites used to activate all technical alerts, with a prompt reaction in case of an out‐of‐range parameter. The threshold for atrial fibrillation (AF) daily burden notification in most cases ranged from 2.4 to 7.2 hours. All ventricular arrhythmias alerts were usually switched on: an inappropriate therapy or more than one appropriate episode triggered an urgent in‐hospital visit. Concerning heart failure, low CRT percentage pacing alert was always used, while the other available notifications were less frequently switched on.

Conclusions

This survey showed that RM service was usually set up with a primary nursing model including on average two responsible physicians and one nurse and mainly offered to ICD/CRT patients. Technical, AF and ventricular arrhythmia alerts triggered prompt reactions, while heart failure related indexes were generally less applied.
Platelet inhibition to target reperfusion injury trial: Rationale and study design
Authors: Bulluck Heerajnarain , Chan Mervyn H. H. , Bryant Jennifer A. , Chai Ping , Chawla Ashish , Chua Terrance S. , Chung Yiu‐Cho , Fei Gao , Ho Hee H. , Ho Andrew F. W. , Hoe Andrew J. , Imran Syed S. , Lee Chi‐Hang , Lim Swee H. , Liew Boon W. , Yun Patrick L. Z. , Hock Marcus O. E. , Paradies Valeria , Roe Matthew T. , Teo Lynette , Wong Aaron S. , Wong Evelyn , Wong Philip E. , Watson Timothy , Chan Mark Y. , Tan Jack W. , Hausenloy Derek J.
Published: November 2018

Background

In ST‐segment elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PPCI), current oral P2Y12 platelet inhibitors do not provide maximal platelet inhibition at the time of reperfusion. Furthermore, administration of cangrelor prior to reperfusion has been shown in pre‐clinical studies to reduce myocardial infarct (MI) size. Therefore, we hypothesize that cangrelor administered prior to reperfusion in STEMI patients will reduce the incidence of microvascular obstruction (MVO) and limit MI size in STEMI patients treated with PPCI.

Methods

The platelet inhibition to target reperfusion injury (PITRI) trial, is a phase 2A, multi‐center, double‐blinded, randomized controlled trial, in which 210 STEMI patients will be randomized to receive either an intravenous (IV) bolus of cangrelor (30 μg/kg) followed by a 120‐minute infusion (4 μg/kg/min) or matching saline placebo, initiated prior to reperfusion (NCT03102723).

Results

The study started in October 2017 and the anticipated end date would be July 2020. The primary end‐point will be MI size quantified by cardiovascular magnetic resonance (CMR) on day 3 post‐PPCI. Secondary endpoints will include markers of reperfusion, incidence of MVO, MI size, and adverse left ventricular remodeling at 6 months, and major adverse cardiac and cerebrovascular events.

The aim of the PITRI trial is to assess whether cangrelor administered prior to reperfusion would reduce acute MI size and MVO, as assessed by CMR.
Design of the randomized, placebo‐controlled evolocumab for early reduction of LDL‐cholesterol levels in patients with acute coronary syndromes (EVOPACS) trial
Authors: Koskinas Konstantinos C. , Windecker Stephan , Buhayer Aliki , Gencer Baris , Pedrazzini Giovanni , Mueller Christian , Cook Stephan , Muller Olivier , Matter Christian M. , Räber Lorenz , Heg Dik , Mach François ,   on behalf of the EVOPACS Investigators
Published: November 2018

Statins lower low‐density lipoprotein cholesterol (LDL‐C) and improve clinical outcomes in patients with atherosclerotic cardiovascular disease (CVD). Patients with acute coronary syndromes (ACS) often do not achieve LDL‐C targets despite potent statin treatment, and have a particularly high risk of early recurrent events. Evolocumab, a proprotein convertase subtilisin/kexin type (PCSK9)‐inhibitor resulting in rapid, marked LDL‐C reduction, has been studied in hypercholesterolemic subjects without CVD and stabilized patients with CVD; the feasibility, safety, and efficacy of this treatment initiated in the acute phase of ACS remain unknown. We report the design of evolocumab for early reduction of LDL‐cholesterol levels in patients with ACS (EVOPACS), a phase‐3, multicenter, randomized, double‐blind, placebo‐controlled trial to assess the feasibility, safety, and LDL‐C‐lowering efficacy of evolocumab on top of atorvastatin 40 mg in patients with ACS. The primary endpoint is percent change in LDL‐C from baseline to 8 weeks. Secondary endpoints are adverse events and serious adverse events. Against a background of beneficial cardiovascular effects of statins beyond LDL‐C lowering and in view of preclinical evidence of similar effects of PCSK9 inhibition, the study will also address a variety of exploratory endpoints including the change in C‐reactive protein and other inflammatory biomarkers; platelet reactivity; and occurrence of contrast‐induced acute kidney injury and myocardial injury in patients undergoing cardiac catheterization. An intracoronary imaging sub‐study will investigate the change from baseline in the lipid core burden index in non‐culprit lesions, as assessed by serial near‐infrared spectroscopy. Recruitment began in January 2018 and enrollment of 308 patients is planned.
Isocitrate dehydrogenase 1 and 2 mutations, 2‐hydroxyglutarate levels, and response to standard chemotherapy for patients with newly diagnosed acute myeloid leukemia
Authors: Brunner Andrew M. , Neuberg Donna S. , Wander Seth A. , Sadrzadeh Hossein , Ballen Karen K. , Amrein Philip C. , Attar Eyal , Hobbs Gabriela S. , Chen Yi‐Bin , Perry Ashley , Connolly Christine , Joseph Christelle , Burke Meghan , Ramos Aura , Galinsky Ilene , Yen Katharine , Yang Hua , Straley Kimberly , Agresta Sam , Adamia Sophia , Borger Darrell R. , Iafrate Anthony , Graubert Timothy A. , Stone Richard M. , Fathi Amir T.
Published: November 2018

Background

Acute myeloid leukemia (AML) cells harboring mutations in isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) produce the oncometabolite 2‐hydroxyglutarate (2HG). This study prospectively evaluated the 2HG levels, IDH1/2 mutational status, and outcomes of patients receiving standard chemotherapy for newly diagnosed AML.

Methods

Serial samples of serum, urine, and bone marrow aspirates were collected from patients newly diagnosed with AML, and 2HG levels were measured with mass spectrometry. Patients with baseline serum 2HG levels greater than 1000 ng/mL or marrow pellet 2HG levels greater than 1000 ng/2 × 106 cells, which suggested the presence of an IDH1/2 mutation, underwent serial testing. IDH1/2 mutations and estimated variant allele frequencies were identified. AML characteristics were compared with the Wilcoxon test and Fisher’s exact test. Disease‐free survival and overall survival (OS) were evaluated with log‐rank tests and Cox regression.

Results

Two hundred and two patients were treated for AML; 51 harbored IDH1/2 mutations. IDH1/2‐mutated patients had significantly higher 2HG levels in serum, urine, bone marrow aspirates, and aspirate cell pellets than wild‐type patients. A serum 2HG level greater than 534.5 ng/mL was 98.8% specific for the presence of an IDH1/2 mutation. Patients with IDH1/2‐mutated AML treated with 7+3‐based induction had a 2‐year event‐free survival (EFS) rate of 44% and a 2‐year OS rate of 57%. There was no difference in complete remission rates, EFS, or OS between IDH1/2‐mutated and wild‐type patients. Decreased serum 2HG levels on day 14 as a proportion of the baseline were significantly associated with improvements in EFS (P = .047) and OS (P = .019) in a multivariate analysis.

Conclusions

Among patients with IDH1/2‐mutated AML, 2HG levels are highly specific for the mutational status at diagnosis, and they have prognostic relevance in patients receiving standard chemotherapy.
Entinostat finds a path: A new study elucidates effects of the histone deacetylase inhibitor on the immune system
Authors: Surolia Ira , Bates Susan E.
Published: November 2018

In this issue, Smith and colleagues demonstrate the antitumor effects of entinostat in an ovarian cancer model and reveal how the drug effects are mediated by the immune system. These studies finally have the potential to translate the unique activity of histone deacetylase inhibitors to solid tumors.
Pre‐Processing MALDI/TOF Mass Spectra by Using Geena 2
Authors: Romano P. , Profumo A. , Facchiano A.
Published: November 2018

Geena 2 is a tool for filtering, averaging, and aligning MALDI/TOF mass spectra, designed to assist scientists in the analysis of high volumes of data and support them for comparative studies. Three web interfaces are available with different levels of complexity. In this manuscript, we explain how to use Geena 2 with these three interfaces to perform analyses of one's own data. Two support protocols showing how to check the example input file and how to create an input file with own data are also presented. © 2018 by John Wiley & Sons, Inc.
Fe,N‐Codoped Graphdiyne Displaying Efficient Oxygen Reduction Reaction Activity
Authors: Si Wenyan , Yang Ze , Wang Xin , Lv Qing , Zhao Fuhua , Li Xiaodong , He Jianjiang , Long Yunze , Gao Juan , Huang Changshui
Published: November 2018

On account of the high‐cost of platinum, researchers are working to develop a new catalyst that is cheaper and has a catalytic effect equivalent to platinum. Herein, owing to the unique acetylenic bonds in graphdiyne, iron, nitrogen co‐doped graphdiyne (Fe‐N‐GDY) is a promising nonprecious metal catalyst, which has been developed with just a small amount of iron precursor with the plan to substitute it for Pt‐based catalysts. The as‐synthesized Fe‐N‐GDY composited catalyst shows excellent catalytic performance with the onset potential of 0.94 V versus reversible hydrogen electrode and limited current density of 5.4 mA cm−2. Moreover, it shows excellent resistance to methanol poisoning and stability in both acidic and alkaline electrolytes, which makes potentially applicable in the oxygen reduction reaction field.
Variable density formation by intense microwave beams near the critical density
Authors: Hashemzadeh M.
Published: November 2018

Modification of electron density of an inhomogeneous, unmagnetized plasma by the relativistic ponderomotive force of intense microwave beams near the critical density is studied. Using the Maxwell and fluid equations and taking into account the relativistic mass, relativistic ponderomotive force, linear inhomogeneity for electron temperature, and tangential inhomogeneity for electron density, the non‐linear electron density, non‐linear dielectric permittivity, and non‐linear wave equations are derived. Results show that positive and negative values of σ1 and σ2 (degree of inhomogeneity of the background electron density and electron temperature, respectively) parameters can affect the electric and magnetic field profiles. In addition, profiles of the non‐linear electron density indicate that by decreasing the σ1 parameter, the amplitude of the peaks increases near the critical density. For positive values of the σ2 parameter, by increasing this parameter the amplitude of the peaks increases, while for negative values of the σ2 parameter, by decreasing this parameter the amplitude of the peaks increases.
Concurrent detection of lysosome and tissue transglutaminase activation in relation to cell cycle position during apoptosis induced by different anticancer drugs
Authors: Halicka H. Dorota , Li Jiangwei , Zhao Hong , Darzynkiewicz Zbigniew
Published: November 2018

Described is the new cytometric approach do detect either stimulation or a collapse of lysosomal proton pump (lysosomes rupture) combined with activation of transglutaminase 2 (TG2) during induction of apoptosis. Apoptosis of human lymphoblastoid TK6 cells was induced by combination of 2‐deoxyglucose with the isoquinoline alkaloid berberine, by DNA topoisomerase I inhibitor camptothecin, its analog topotecan, topoisomerase II inhibitors etoposide or mitoxantrone, as well as by the cytotoxic anticancer ribonuclease ranpirnase (onconase). Activity of the proton pump of lysosomes was assessed by measuring entrapment and accumulation of the basic fluorochrome acridine orange (AO) resulting in its metachromatic red luminescence (F>640) within these organelles. Activation of TG2 was detected in the same cell subpopulation by the evidence of crosslinking of cytoplasmic proteins revealed by the increased intensity of the side light scatter (SSC) as well as following cell lysis by detergent, by its red fluorescence after staining by sulforhodamine 101. Because at low AO concentration nuclear DNA of the lysed cells was stoichiometrically stained green (F530) its quantity provided information on effects of the drug treatments on cell cycle in relation to activation of TG2. The data reveal that activation of lysosomal proton pump was evident in subpopulations of cells treated with 2‐deoxyglucose plus berberine, topotecan, etoposide and mitoxantrone but not with ranpirnase. The collapse of lysosomal proton pump possibly reporting rupture of these organelles was observed in definite cell subpopulations after treatment with each of the studied drugs. Because regardless of the inducer of apoptosis TG2 activation invariably was correlated with lysosomes rupture it is likely that it was triggered by calcium ions or protons released from the ruptured lysosomes. This new methodological approach offers the means to investigate mechanisms and factors affecting autophagic lysosomes proton pump activity vis‐à‐vis TG2 activation that are common in several pathological states. © 2019 International Society for Advancement of Cytometry
Drug sales confirm clinical advantage of multi‐target inhibition of drug escapes by anticancer kinase inhibitors
Authors: Chen Shangying , Yang Sheng Yong , Chen Zhe , Tan Ying , Jiang Yu Yang , Chen Yu Zong
Published: November 2018

The clinical advantage of co‐targeting cancer drug escape has been indicated by the percentage of these co‐targeting drugs among all multi‐target drugs in clinics and clinical trials. This clinical advantage needs to be further interrogated from such perspectives as the clinical impact of multi‐target inhibition of drug‐escape mediators. This impact may be reflected by drug sales data, that is, multi‐target inhibition of higher number of drug‐escape mediators favors the expanded coverage of drug‐resistant patients leading to higher sales. We investigated whether this expectation is followed by the 25 FDA‐approved anticancer kinase inhibitors, which were divided into 11 groups of comparable therapeutic mechanisms and approval years. We found 19 (76%) drugs to follow and 3 (12%) drugs not to follow this expectation. The remaining two (8%) and one (4%) drugs cannot be assessed due to insufficient data and incomparability. Therefore, drug sales strongly indicate the clinical advantage of multi‐target inhibition of cancer drug escapes.
Heterogeneous bonding between cyclo‐olefin polymer (COP) and glass‐like substrate by newly developed water vapor‐assisted plasma, Aqua Plasma Cleaner
Authors: Terai Hirokazu , Funahashi Risa , Hashimoto Taichi , Kakuta Masaya
Published: November 2018

To develop high‐performance and low‐cost microfluidic devices, heterogeneous bonding with cyclo‐olefin polymer (COP) and glass substrate was investigated by low‐pressure plasma using water vapor. COP and glass‐like substrate were bonded at room temperature under its own weight, and the bonding strength reached the breaking point of base material strength. Water contact angle of the COP and glass surface after water vapor plasma was less than 1° (superhydrophilic) and showed stable hydrophilicity even after 30 days. Water vapor plasma and COP surface were analyzed by optical emission spectroscopy (OES) and x‐ray photoelectron spectroscopy (XPS) to study the reaction of room temperature bonding.
Comparison of Insulin Determination on NiNPs/chitosan‐ MWCNTs and NiONPs/chitosan‐MWCNTs Modified Pencil Graphite Electrode
Authors: Šišoláková Ivana , Hovancová Jana , Oriňaková Renáta , Oriňak Andrej , Rueda Garcia Daniel , Shylenko Oleg , Radoňák Jozef
Published: November 2018

The rising amount of patients suffering for diabetes mellitus increases the requirements for effective insulin sensors. Carbon materials are a suitable choice for the development of insulin sensors due to their electrochemical characteristics. Pencil graphite electrodes (PGE) represent the trade‐off between price and excellent conductive properties. The modification of PGE by NiO and Ni nanoparticles fixed by chitosan results in surface area enlargement and improved electrocatalytic properties. This paper is focused on the comparison of different properties of Ni and NiO nanoparticles and their effect on redox reaction mechanism of insulin and detection characteristics. The electrode modified by Ni nanoparticles displays linear range of 1 μM–5 μM (R2 0.80), limit of detection (LOD) of 4.34 μM and sensitivity of 0.12 μA/μM. On the other hand, the electrode modified by NiO nanoparticles displays enhanced electrochemical characteristics such as linear range of 0.05 μM–5 μM (R2 0.99), limit of detection of 260 nM and sensitivity of 0.64 μA/μM. These properties make the NiO nanoparticles modified PGE the appropriate candidate for insulin determination.
Selecting indicator species for biodiversity management
Authors: Bal Payal , Tulloch Ayesha IT , Addison Prue FE , McDonald‐Madden Eve , Rhodes Jonathan R
Published: November 2018

Indicator species are frequently used for biodiversity management but whether indicator species selection is explicit about their ability to improve management decisions remains unclear. We reviewed the scientific literature to assess whether existing methods for selecting indicator species account for the following five monitoring and management “decision factors”: objectives, constraints, actions, uncertainties, and biodiversity outcomes. Of the selected studies, most focused only on improving monitoring efficiency rather than on management effectiveness, potentially leading to ineffective indicators for decision making; only 21% of the studies explicitly accounted for management objectives and actions. Crucially, 94% of the reviewed studies and one‐half of all indicator selection methods overlooked constraints (eg budgets), as well as uncertainties in indicator responses to management. To improve selection of indicator species, we suggest a systematic approach using key concepts from structured decision making. This approach facilitates explicitly evaluating management outcomes as part of the indicator species selection process and allows for the review of indicator choices over time to improve future monitoring and management decisions.
Weedy futures: can we benefit from the species that thrive in the marine Anthropocene?
Authors: Doubleday Zoë A , Connell Sean D
Published: November 2018

Humans are changing the marine environment at an accelerating rate, causing species decline and loss of natural resources. But counter to these declining trends, some species appear to be thriving in response to environmental change. Focusing on three divergent taxa – algae, jellyfish, and cephalopods – we discuss the concept of adaptable “weedy species” and how they may be the ultimate beneficiaries of rapidly changing marine environments. We then show how such species could benefit society, not only by absorbing human impacts and providing sustainable forms of food, but also by reducing pressure on species in decline. As the world's demand for natural resources continues to grow in a global environment under increasing strain, we should take a closer look at weedy species to see what they can provide.
Responding to climate change in forest management: two decades of recommendations
Authors: Hagerman Shannon M , Pelai Ricardo
Published: November 2018

Recommendations for responding to climate change in forest management have proliferated over the past two decades. A systematic review of the scientific literature revealed that the majority of such recommendations (86%) focused primarily on maintaining existing ecological patterns and processes via either passive or active adaptation approaches, while 14% focused on transformation to new system configurations through active interventions. Most recommendations (69%) were general, non‐specific principles and derived from research conducted in North America or Europe. These findings highlight the need for (1) more actionable recommendations and diversification in geographic inquiry, specifically in Asia, Africa, Oceania, Latin America, and the Caribbean; (2) increased contributions from social science and mixed social–ecological inquiry; and (3) governance processes that enhance dialogue among stakeholders to better anticipate and navigate the trade‐offs implied by potential future forests in the decades to come.
Participatory Action Research as a Framework for Transdisciplinary Collaboration: A Pilot Study on Healthy, Sustainable, Low‐Income Housing in Delhi, India
Authors: Nix Emily , Paulose Jacob , Shrubsole Clive , Altamirano‐Medina Hector , Belesova Kristine , Davies Michael , Khosla Renu , Wilkinson Paul
Published: November 2018

To tackle global challenges, research collaborations need to integrate multiple disciplinary perspectives and connect with local practices to find solutions that are sustainable and impactful. This paper discusses how participatory action research (PAR) is used as a framework for transdisciplinary collaboration to integrate different disciplines and identify healthy and sustainable housing solutions appropriate for local development practices and policy. By analyzing a transdisciplinary research collaboration investigating housing interventions for low‐income settlements in Delhi, reflections and recommendations are provided for other projects wishing to use a similar methodology. It is found that the PAR framework has successfully guided the integration of contrasting methods and improved the impact of research outcomes, resulting in the emergence of new shared practices. However, it proves to be challenging and requires heightened communication and engagement to achieve understanding between all disciplines and practices. It is recommended that focus is given to developing relationships and effective communication channels and that time should be preallocated for reflection. The work provides insights for integrating academic disciplines, the community, and relevant stakeholders in the cocreation of evidence that is paramount to formulate effective solutions to global challenges.
Covalent Grafting Terbium Complex to Alginate Hydrogels and Their Application in Fe3+ and pH Sensing
Authors: Zhang Zeyu , Liu Fengyi , Xu Quanqing , Zhu Han , Zhu Aixin , Kou Junfeng
Published: November 2018

Biocompatible luminescent hydrogels containing covalently linked terbium complexes with a macrocyclic ligand are prepared by a facile method. The environmentally friendly preparation procedure is carried out at room temperature using water as a solvent. These new hybrid materials can act as luminescent sensors to detect Fe3+ with relative selectivity and high sensitivity. The hydrogels also show pH sensing with a wide range.
Pattern of planned systemic therapy usage in newly diagnosed, nonmetastatic squamous cell carcinoma of the head and neck in a commercially insured population in the United States
Authors: Park Jong Chul , Gourin Christine G. , Kiess Ana P. , Mehra Ranee , Forastiere Arlene A. , Kang Hyunseok
Published: November 2018

Background

We analyzed systemic therapy plans submitted for commercially insured patients with untreated, newly diagnosed squamous cell carcinoma of the head and neck (SCCHN) to investigate patterns of practice.

Methods

Consecutive chemotherapy treatment plans were submitted using Eviti Connect (https://www.marylandphysicianscare.com/content/dam/centene/maryland/pdfs/evitiConnectFactSheet.pdf) portal for preauthorization between June 1, 2011, and June 30, 2015, were analyzed.

Results

A total of 387 treatment plans were submitted for 340 patients; 68 and 272 patients were from academic centers and community practices, respectively. Single agent cisplatin (57%), cetuximab (18%), and carboplatin (9%) were the most commonly proposed regimens concurrent with definitive radiotherapy (RT). The frequency of cetuximab use was not significantly different between academic centers and community practices. A clinical trial was proposed in only 15% of patients.

Conclusion

Among commercially insured patients with newly diagnosed, nonmetastatic SCCHN, the choice of systemic therapy in initial treatment plans was not significantly different between academic centers and community practices. Clinical trials are underutilized and should be encouraged.
Patterns of failure after postoperative intensity‐modulated radiotherapy for locally advanced buccal cancer: Initial masticator space involvement is the key factor of recurrence
Authors: Lin Yu‐Wei , Chen Ya‐Fang , Yang Ching‐Chieh , Ho Chung‐Han , Wu Tai‐Ching , Yen Ching‐Yu , Lin Li‐Ching , Lee Steve P. , Lee Ching‐Chih , Tai Ming‐Hong
Published: November 2018

Background

The purpose of this study was to determine failure patterns and clinicopathologic prognostic factors in patients with locally advanced buccal cancer after postoperative intensity‐modulated radiotherapy (IMRT).

Methods

Eighty‐two patients with locally advanced (American Joint Committee on Cancer [AJCC] stage III/IV) buccal cancer who underwent surgery followed by postoperative IMRT between January 2007 and October 2012 were retrospectively analyzed.

Results

Eighteen patients had local recurrences as the first recurrent site and 11 had supramandibular notch recurrences; the majority of recurrences were classified as marginal failures. The median time from the first local or regional recurrence to death was 5.9 months. In multivariate analyses of survivals, the initial masticator space involvement was the most important prognostic factor. Masticator space involvement, N classification, and maxillectomy were the significant prognostic predictors for supramandibular notch recurrences.

Conclusion

Postoperative IMRT for buccal cancer should not include the surgical beds alone, rather, it should be based on the potential patterns of spread.
Spectral analysis of continuous redox data reveals geochemical dynamics near the stream–aquifer interface
Authors: Wallace Corey D. , Sawyer Audrey H. , Barnes Rebecca T.
Published: November 2018

Changes in streamflow and water table elevation influence oxidation–reduction (redox) conditions near river–aquifer interfaces, with potentially important consequences for solute fluxes and biogeochemical reaction rates. Although continuous measurements of groundwater chemistry can be arduous, in situ sensors reveal chemistry dynamics across a wide range of timescales. We monitored redox potential in an aquifer adjacent to a tidal river and used spectral and wavelet analyses to link redox responses to hydrologic perturbations within the bed and banks. Storms perturb redox potential within both the bed and banks over timescales of days to weeks. Tides drive semidiurnal oscillations in redox potential within the streambed that are absent in the banks. Wavelet analysis shows that tidal redox oscillations in the bed are greatest during late summer (wavelet magnitude of 5.62 mV) when river stage fluctuations are on the order of 70 cm and microbial activity is relatively high. Tidal redox oscillations diminish during the winter (wavelet magnitude of 2.73 mV) when river stage fluctuations are smaller (on the order of 50 cm) and microbial activity is presumably low. Although traditional geochemical observations are often limited to summer baseflow conditions, in situ redox sensing provides continuous, high‐resolution chemical characterization of the subsurface, revealing transport and reaction processes across spatial and temporal scales in aquifers.