bluuebunny/crossref_metadata_2025 huggingface dataset:
Measuring Critical Thinking in Science: Systematic Review
Authors: Hakim Nur Wahidah Abd , Talib Corrienna Abdul
Published: October 2018

The review aims to explore possible methods for critical thinking assessment in science from previous studies. For a long time, critical thinking has been among most talked topics among researchers and academicians, due to its nature in improving one’s quality of life such as becoming an effective problem solver and logical thinkers. In this study, literature search for related studies was conducted through online databases, The Educational Resource Information Centre (ERIC) dated from the year 2010 till 2017 using keywords such as critical thinking, science, science education and measurement. Only refereed/peer-reviewed journals that fulfilled criteria needed were selected for the study with the findings from web-based service providers, including Sage Journals, Springer, Taylor & Francis, Science Direct, and Wiley Online Library. The findings were analyzed using document analysis technique to answer research questions of this study. This systematic review reveals that critical thinking can be assessed using quantitative or qualitative methods depending on the scope and dimensions of the research. Although there are studies on critical thinking in science, the assessment tools used are instrumented for critical thinking in general setting which focuses in general context. However, when it comes to assessing critical thinking in science secondary school/high school, the findings were limited.
Influence of Major Urban Construction on Atmospheric Particulates and Emission Reduction Measures
Authors: Wang Shunyi , Zhou Ping , Lin Limin , Liu Chuankun , Huang Tao
Published: October 2018

In order to understand the variation of air quality and the concentration of atmospheric particulates in Chengdu Second Ring Road renovation project, this paper starts to investigate the surrounding residents’ opinions on the influenced environment and their daily lives via questionnaires. Then the study numerically simulates the change rule of atmospheric particulates in terms of time and space by using the Gaussian dispersion-deposition model and the compartment model. The optimized scientific scheme is selected by the improved fuzzy analytical hierarchy process (FAHP) to help decision making for the future urban reconstructions. Finally, the reduced emissions of atmospheric particulates are measured when the improvement scheme is provided. According to the study, it can be concluded that the concentration of atmospheric particulates increases rapidly in central Chengdu city during the renovation project, which results in worsening air quality in Chengdu during March 2012 to March 2013. Taking related measures on energy saving and emission reduction can effectively reduce the concentration of atmospheric particulates and promote economic, environmental and social coordination.
Meteorological Factors Affecting Winter Particulate Air Pollution in Ulaanbaatar from 2008 to 2016
Authors: Wang Minrui , Kai Kenji , Sugimoto Nobuo , Enkhmaa Sarangerel
Published: October 2018

Ulaanbaatar, the capital of Mongolia, is subject to high levels of atmospheric pollution during winter, which severely threatens the health of the population. By analyzing surface meteorological data, ground-based LIDAR data, and radiosonde data collected from 2008 to 2016, we studied seasonal variations in particulate matter (PM) concentration, visibility, relative humidity, temperature inversion layer thickness, and temperature inversion intensity. PM concentrations started to exceed the 24-h average standard (50 μg/m3) in mid-October and peaked from December to January. Visibility showed a significant negative correlation with PM concentration. Relative humidity was within the range of 60–80% when there were high PM concentrations. Both temperature inversion layer thickness and intensity reached maxima in January and showed similar seasonal variations with respect to PM concentration. The monthly average temperature inversion intensity showed a strong positive correlation with the monthly average PM2.5 concentration. Furthermore, the temperature inversion layer thickness exceeded 500 m in midwinter and overlaid the weak mixed layer during daytime. Radiative cooling enhanced by the basin-like terrain led to a stable urban atmosphere, which strengthened particulate air pollution.
Proposition of Values for the Client of a Spa Enterprise
Authors: Szromek Adam R.
Published: October 2018

Purpose. The aim of the article is to try to integrate the structure of a spa product and business model of the spa sector, with particular emphasis on the value proposition for the client perceived through the prism of the core benefits in the spa product. Method. Through critical analysis of the literature, the work cites key categories of value configuration and examples for the sector of spa enterprises, and then relates this knowledge to the issue of the structure of a spa product. Findings. As a result of the discussed discussions, a schema of a spa product was developed, with particular emphasis on the core of the product, the actual, extended and potential product, and components of the business model. Research and conclusions limitations. The weakness of the conducted research is their generalization, which although it is intended, paradoxically does not take into account the individual specifics of individual spa plants and the type of spa raw material used in them (salt, peloids, thermal and brine). Practical implications. The article provides a diagram of a spa product integrated with the business model. Originality. Until now, the values for the spa client have not been characterized. The work fills the gap in the core of the spa product in the context of the business model. Type of paper. The work is of a conceptual nature based on literature review and market cases.
Objetos paradoxais desiguais
Authors: Benayon Flavio Da Rocha
Published: October 2018

Ancorado na Análise de Discurso Materialista, de Michel Pêcheux, proponho trabalhar a desigualdade constitutiva da relação entre diferentes objetos paradoxais, especificamente na política institucionalizada. Procedo mobilizando a noção de objetos paradoxais desiguais, formulada a partir de meu encontro com determinados objetos. O percurso que seguirei retoma, primeiramente, análises que desenvolvi apontando os sentidos de revolução no fim da Primeira República Brasileira. Em um segundo momento, analiso os sentidos de mudança no segundo turno das eleições de 2014, no Brasil. Em uma terceira parte, aponto possíveis relações entre revolução e mudança na constituição dos objetos paradoxais desiguais.
O Conservadorismo como ideologia: Contribuições da ciência das redes para a linguística sistêmico funcional
Authors: Lima Lopes Rodrigo Esteves de
Published: October 2018

Tenho por objetivo discutir sobre o discurso do ódio em uma Mídia Social. O corpus de pesquisa é composto por mais de 9.000 comentários resposta ao anúncio de uma exposição de Queer Art em um museu porto-alegrense. Tenho como fundamentação a Sistêmico e a Avaliatividade, utilizando de procedimentos da Ciência das Redes para análise das interações e dos dados linguísticos. Resultados demonstram a criação de um sistema de representação baseado na oposição entre exposição e os valores religiosos, levando a estratégias baseadas na sua demonização, além de enxovalhos dirigidos a artistas, curadores e a entidade patrocinadora.
A política brasileira de integração dos povos indígenas: o discurso integracionista materializado no arquivo jurídico
Authors: Cabrera Bruna Cielo , Scherer Amanda Eloina
Published: October 2018

Em consonância com o arcabouço teórico-metodológico da Análise de Discurso, debruçamo-nos sobre o Estatuto do Índio (Lei 6.001, 19 de dezembro de 1973) e seu autodeclarado propósito de promover a integração dos povos indígenas à comunhão nacional. Buscamos compreender quais os efeitos de sentido que derivam de integração no discurso que se constitui no/pelo Estatuto através da tutela da capacidade civil indígena estabelecida nesta legislação. Tomamos a noção de arquivo pecheutiana como procedimento teórico-metodológico para tratamento dos materiais elencados para análise, sendo recortadas sequências discursivas para compor o corpus, que se organizam em função de relações parafrásticas e polissêmicas.
Authentication and Authorization for Constrained Environments (ACE) com Framework OAuth e Protocolo CoAP
Authors: Porciúncula Cleber Bittencourt , Beskow Sílvio , Rocha Érico Santos , Nobre Jeferson Campos
Published: October 2018

O presente artigo tem por objetivo estudar o framework ACE (Authentication and Authorization for Constrained Environments) utilizando o framework OAuth 2.0 e o protocolo CoAP. O grupo analisado explora conceitos como autenticação e autorização em ambientes restritos a conexão. Este framework, engloba um conjunto de protocolos que estão em estudo para uma padronização na utilização em dispositivos IoT. Dispositivos restritos formam redes de comunicação trocando informações entre si, necessitando de requisitos de segurança para a garantir confidencialidade, integridade e disponibilidade.
Withdrawal: Short-term gains in histology knowledge: A veterinary gaming application
Authors: Bauman Eric B. , Gilbert Gregory E , Vaughan Greg
Published: October 2018

Withdrawal Notice: This article is withdrawn at the authors’ request.
Infection and coinfection by human papillomavirus, Epstein–Barr virus and Merkel cell polyomavirus in patients with squamous cell carcinoma of the larynx: a retrospective study
Authors: Vazquez-Guillen Jose Manuel , Palacios-Saucedo Gerardo C. , Rivera-Morales Lydia Guadalupe , Alonzo-Morado Monica Valeria , Burciaga-Bernal Saira Berenice , Montufar-Martinez Maribel , Ortiz-Lopez Rocio , Gonzalez-Villasana Vianey , Martinez-Torres Ana Carolina , Serna-Hernandez Julio Cesar , Hernandez-Martinez Silvia Judith , Castelan-Maldonado Edmundo Erbey , Zavala-Pompa Angel , Montalvo-Bañuelos Martha Socorro , Garcia-Cabello Ricardo , Sanchez-Fresno Ethel Corinthia , Rodriguez-Padilla Cristina
Published: October 2018

Background

Human papillomavirus (HPV) is recognized as an important risk factor for laryngeal carcinogenesis. Although HPV-16 and 18 have been strongly implicated, the presence of other high-risk HPV (HR-HPV) genotypes or the coinfection with Epstein-Barr virus (EBV) or Merkel cell polyomavirus (MCPV) may increase the risk, but their etiological association has not been definitively established.

Methods

We characterized the genotype-specific HPV and the frequency of EBV and MCPV infections through the detection of their DNA in 195 laryngeal specimens of squamous cell carcinoma (SCC) histologically confirmed.

Results

HPV DNA was detected in 93 (47.7%) specimens. HPV-11 was the most frequent with 68 cases (73.1%), and HPV-52 was the most frequently HR-HPV found with 51 cases, which corresponds to 54.8% of all HPV-positive specimens. EBV DNA was detected in 54 (27.7%) tumor tissue specimens of which 25 (46.3%) were in coinfection with HPV. MCPV DNA was detected only in 11 (5.6%) cases of which 5 (45.4%) were in coinfection with an HR-HPV. No association between the presence of DNA of the three examined viruses and the patient smoking habits, alcohol consumption, age, the keratinization status, differentiation grade, or localization of the tumor in the larynx were found.

Discussion

HPV-52 was the most prevalent HR-HPV, which may suggest that this and other genotypes in addition to HPV-16 and 18 could be considered for prophylaxis. However, further studies including non-cancer larynx cases and the evaluation of other molecular markers and viral co-infection mechanisms are needed to determine the role of the different HR-HPV genotypes, EBV, and MCPV in the etiology of SCC of the larynx.
Clinical implementation of Dosimetry Check™ for TomoTherapy® delivery quality assurance
Authors: Chung Eunah , Kwon Dongyeol , Park Taeyang , Kang Hyeri , Chung Yoonsun
Published: October 2018

Purpose

The delivery quality assurance (DQA) of intensity‐modulated radiotherapy (IMRT) plans is a prerequisite for ensuring patient treatments. This work investigated the clinical usefulness of a new DQA system, Dosimetry Check™(DC), on TomoTherapy®‐based helical IMRT plans.

Methods

The DQA was performed for 15 different TomoTherapy®‐based clinical treatment plans. In Tomotherapy® machines, the couch position was set to a height of 400 mm and the treatment plans were delivered using QA‐Treatment mode. For each treatment plan, the plan data and measured beam fluence were transferred to a DC‐installed computer. Then, DC reconstructed the three‐dimensional (3D) dose distribution to the CT images of the patient. The reconstructed dose distribution was compared with that of the original plan in terms of absolute dose, two‐dimensional (2D) planes and 3D volume. The DQA results were compared with those performed by a conventional method using the cheese phantom with ion chamber and radiochromic film.

Results

For 14 out of the 15 treatment plans, the absolute dose difference between the measurement and calculation was less than 3% and the gamma pass rate with the 3%/3 mm gamma evaluation criteria was greater than 95% for both DQA methods. The P‐value calculated using Wilcoxon signed‐rank test was 0.256, which implies no statistically significance in determining the absolute dose difference between the two methods. For one treatment plan generated using the 5.0 cm field width, the absolute dose difference was greater than 3% and the gamma pass rate was less than 95% with DC, while the DQA result with the cheese phantom method passed our TomoTherapy® DQA tolerance.

Conclusion

We have clinically implemented DC for the DQA of TomoTherapy®‐based helical IMRT treatment plans. DC carried out the accurate DQA results as performed with the conventional cheese phantom method. This new DQA system provided more information in verifying the dose delivery to patients, while simplifying the DQA process.
All‐Fabric Wearable Electroadhesive Clutch
Authors: Ramachandran Vivek , Shintake Jun , Floreano Dario
Published: October 2018

A lightweight, textile fabricated, haptic device consisting of an electrostatic adhesive clutch is introduced, which can constrain body movement when activated at low power (≈1 mW). The clutch electrodes are composite structures, prepared by coating copper‐plated polyester fabric with thin films of high‐κ dielectric ink. When voltage is applied across a pair of overlapping electrodes, the charge separation created between the overlapped surfaces gives rise to adhesive forces that resist tensile loads along the electrode surface. The clutch is arranged in parallel with a sheet of knitted fabric, which exhibits low‐stiffness spring‐like characteristics, thus decreasing load resistance when the clutch is deactivated. Mechanical tests are carried out to assess the dependency on scaling and loading rate at different voltages. The load‐bearing capacity of the device is experimentally shown to sustain a 10 kg load for a clutch pair with 120 × 70 mm2 dielectric overlap, when activated at 400 V. Current‐dependent charging and discharging times that can be as low as 15 ms are presented. To exemplify its pertinence in wearable applications, the device is used as an elbow joint constraint, exhibiting its conformability to curvatures and suitability for skin‐mounted applications.
Efficacy and Safety of Ixekizumab in the Treatment of Radiographic Axial Spondyloarthritis: Sixteen‐Week Results From a Phase III Randomized, Double‐Blind, Placebo‐Controlled Trial in Patients With Prior Inadequate Response to or Intolerance of Tumor Necrosis Factor Inhibitors
Authors: Deodhar Atul , Poddubnyy Denis , Pacheco‐Tena Cesar , Salvarani Carlo , Lespessailles Eric , Rahman Proton , Järvinen Pentti , Sanchez‐Burson Juan , Gaffney Karl , Lee Eun Bong , Krishnan Eswar , Santisteban Silvia , Li Xiaoqi , Zhao Fangyi , Carlier Hilde , Reveille John D. ,   the COAST‐W Study Group
Published: October 2018

Objective

To investigate the efficacy and safety of ixekizumab in patients with active radiographic axial spondyloarthritis (SpA) and prior inadequate response to or intolerance of 1 or 2 tumor necrosis factor inhibitors (TNFi).

Methods

In this phase III randomized, double‐blind, placebo‐controlled trial, adult patients with an inadequate response to or intolerance of 1 or 2 TNFi and an established diagnosis of axial SpA (according to the Assessment of SpondyloArthritis international Society [ASAS] criteria for radiographic axial SpA, with radiographic sacroiliitis defined according to the modified New York criteria and ≥1 feature of SpA) were recruited and randomized 1:1:1 to receive placebo or 80‐mg subcutaneous ixekizumab every 2 weeks (IXEQ2W) or 4 weeks (IXEQ4W), with an 80‐mg or 160‐mg starting dose. The primary end point was 40% improvement in disease activity according to the ASAS criteria (ASAS40) at week 16. Secondary outcomes and safety were also assessed.

Results

A total of 316 patients were randomized to receive placebo (n = 104), IXEQ2W (n = 98), or IXEQ4W (n = 114). At week 16, significantly higher proportions of IXEQ2W patients (n = 30 [30.6%]; P = 0.003) or IXEQ4W patients (n = 29 [25.4%]; P = 0.017) had achieved an ASAS40 response versus the placebo group (n = 13 [12.5%]), with statistically significant differences reported as early as week 1 with ixekizumab treatment. Statistically significant improvements in disease activity, function, quality of life, and spinal magnetic resonance imaging–evident inflammation were observed after 16 weeks of ixekizumab treatment versus placebo. Treatment‐emergent adverse events (AEs) with ixekizumab treatment were more frequent than with placebo. Serious AEs were similar across treatment arms. One death was reported (IXEQ2W group).

Conclusion

Ixekizumab treatment for 16 weeks in patients with active radiographic axial SpA and previous inadequate response to or intolerance of 1 or 2 TNFi yields rapid and significant improvements in the signs and symptoms of radiographic axial SpA versus placebo.
Place of death for patients with cancer in the United States, 1999 through 2015: Racial, age, and geographic disparities
Authors: Chino Fumiko , Kamal Arif H. , Leblanc Thomas W. , Zafar S. Yousuf , Suneja Gita , Chino Junzo P.
Published: October 2018

BACKGROUND

Place of death is an essential component of high quality cancer care and comprehensive national trends and disparities in place of death are unknown.

METHODS

Deidentified death certificate data were obtained via the National Center for Health Statistics. All cancer deaths from 1999 through 2015 were included. Multivariate logistic regression was used to test for disparities in place of death associated with sociodemographic variables.

RESULTS

From 1999 through 2015, a total of 9,646,498 cancer deaths occurred. Hospital deaths decreased (from 36.6% to 24.6%), whereas the rate of home deaths (38.4% to 42.6%) and hospice facility deaths (0% to 14.0%) both increased (all P<.001). On multivariate logistic regression, all assessed variables were found to be associated with place of death. Specifically, younger age (age birth‐14 years: odds ratio [OR], 2.39; age 25‐44 years: OR, 1.62), black (OR, 1.83) or Asian (OR, 1.74) race, and Hispanic ethnicity (OR, 1.41) were associated with hospital death. Being married (OR, 2.17) or widowed (OR, 1.56) was associated with home death whereas increasing educational level (OR, 1.15‐1.19) was associated with hospice death (all P<.001). Despite overall improvements, certain disparities were found to increase. For young patients, the likelihood of a hospital death increased from 2.3 times to 3.4 times that of older patients (50.9% for those aged 15‐24 years vs 15.0% for those aged ≥85 years in 2015). For black patients, the likelihood of a hospital death increased from 1.29 times to 1.42 times that of white patients (32.8% for black patients vs 23.1% for white patients in 2015).

CONCLUSIONS

Hospital cancer deaths decreased by approximately one‐third with commensurate increases in home and hospice facility deaths. Many sociodemographic groups experience significant disparities with regard to place of death and may benefit from targeted efforts to improve goal‐concordant care.
Real‐world testing and treatment patterns in chronic lymphocytic leukemia: A SEER patterns of care analysis
Authors: Seymour Erlene K. , Ruterbusch Julie J. , Beebe‐Dimmer Jennifer L. , Schiffer Charles A.
Published: October 2018

Background

Laboratory testing and treatments for chronic lymphocytic leukemia (CLL) have changed dramatically within the last decade. The authors evaluated changes in patterns of real‐world testing and treatment over time by comparing 2 population‐based cohorts.

Methods

The National Cancer Institute–sponsored Patterns of Care study was conducted among patients with CLL who were sampled from 14 Surveillance, Epidemiology, and End Results (SEER) program registries. Demographics, testing, and treatment data were abstracted from medical records within 24 months of diagnosis.

Results

A total of 1008 patients diagnosed in 2008 and 1367 patients diagnosed in 2014 were included. There was a significant increase in fluorescence in situ hybridization (FISH) testing, immunoglobulin heavy‐chain variable region gene (IgVH) mutation analyses, and lymph node biopsies between 2008 and 2014. FISH testing was performed in the majority of, but not all, treated patients (53% in 2008, which increased to 62% in 2014). Some differences in the receipt of FISH testing by age and insurance status were observed over time (older patients and Medicare patients without private insurance were less likely to be tested in 2014). There were contrasting testing patterns noted by practice type and year, with nonteaching hospitals more likely to perform bone marrow biopsies in 2008, and teaching hospitals more likely to perform FISH and IgVH testing in 2014. There also were differences in treatments over time, with the use of bendamustine and rituximab being more common in 2014, at the expense of fludarabine, cyclophosphamide, and rituximab.

Conclusions

There have been rapidly changing practices in the testing and treatment patterns of patients with CLL within the last decade.
The treasure of now and an uncertain future: Delay discounting and health behaviors among cancer survivors
Authors: Sheffer Christine E. , Miller Austin , Bickel Warren K. , Devonish Julia A. , O’Connor Richard J. , Wang Chong , Rivard Cheryl , Gage‐Bouchard Elizabeth A.
Published: October 2018

Background

The identification of new therapeutic targets to improve health behaviors among cancer survivors (CS) is likely to improve cancer treatment outcomes. Delay discounting (DD) rate is the degree to which one devalues rewards as a function of time to receipt. Lower DD rates (ie, prioritizing long‐term over immediate rewards) are associated with healthier behaviors. CS often experience distress and thoughts of early mortality that can potentially shift priorities to the present and negatively impact DD rates, especially when newly diagnosed. Understanding relations between DD and health behaviors among CS will contribute to the examination of DD as a therapeutic target for improving health behaviors for CS.

Method

CS (n = 1001) were recruited from a web panel and administered a web‐based questionnaire. Multivariate models examined relations among DD rate, years since diagnosis, and 10 health behavior indicators. We hypothesized that 1) higher DD rates would be associated with fewer years since diagnosis, and 2) lower DD rates would be associated with healthier behaviors, moderated by years since diagnosis.

Results

In general, higher DD rates were associated with fewer years since diagnosis. Higher DD rates were associated with more alcohol consumption, cigarette smoking, other tobacco use, tanning booth use, and conversely, greater adherence to annual primary care visits. A significant interaction between DD rate and years since diagnosis was not found.

Conclusion

Lower DD rates are associated with several important healthy lifestyle behaviors. DD rate is a promising therapeutic target for new interventions to improve multiple health behaviors among CS.
A pooled analysis of individual patient data from National Clinical Trials Network clinical trials of concurrent chemoradiotherapy for limited‐stage small cell lung cancer in elderly patients versus younger patients
Authors: Stinchcombe Thomas E. , Fan Wen , Schild Steven E. , Vokes Everett E. , Bogart Jeff , Le Quynh‐Thu , Thomas Charles R. , Edelman Martin J. , Horn Leora , Komaki Ritsuko , Cohen Harvey J. , Kishor Ganti Apar , Pang Herbert , Wang Xiaofei
Published: October 2018

Background

Platinum and etoposide with thoracic radiation followed by prophylactic cranial irradiation constitute the standard treatment for limited‐stage small cell lung cancer (LS‐SCLC). Many patients with LS‐SCLC are elderly with comorbidities.

Methods

Individual patient data were collected from 11 phase 2 or 3 trials for LS‐SCLC conducted by the National Clinical Trials Network and activated from 1990 to 2010. The primary endpoint was overall survival (OS); the secondary endpoints were progression‐free survival (PFS), the rate of severe adverse events, and off‐treatment reasons. The outcomes were compared for patients 70 years old or older (elderly patients) and patients younger than 70 years (younger patients).

Results

Individual patient data from 1049 younger patients (81%) and 254 elderly patients (19%) were analyzed. In the multivariate model, elderly patients, in comparison with younger patients, had worse OS (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.18‐1.63; median OS for elderly patients, 17.8 months; OS for younger patients, 23.5 months) and worse PFS (HR, 1.19; 95% CI, 1.03‐1.39; median PFS for elderly patients, 10.6 months; median PFS for younger patients, 12.3 months). Elderly patients, in comparison with younger patients, experienced more grade 5 adverse events (8% vs 3%; P < .01) and more grade 3 or higher dyspnea (11% vs 7%; P = .03) but less grade 3 or higher esophagitis/dysphagia (14% vs 19%; P = .04) and less grade 3 or higher vomiting (11% vs 17%; P = .01). Elderly patients completed treatment less often, discontinued treatment because of adverse events and patient refusal more frequently, and died during treatment more frequently.

Conclusions

Elderly patients with LS‐SCLC have worse PFS and OS and more difficulty in tolerating therapy. Future trials should incorporate assessments of elderly patients, novel monitoring of adverse events, and more tolerable radiation and systemic therapies.
Reducing DNA damage by formaldehyde in liquid‐based cytology preservation solutions to enable the molecular testing of lung cancer specimens
Authors: Matsuo Yukiko , Yoshida Tsutomu , Yamashita Kazuya , Satoh Yukitoshi
Published: October 2018

Background

Liquid‐based cytology (LBC) is a useful cytopathological method, and LBC lung adenocarcinoma specimens may be used for genetic analysis in the near future. In the current study, the authors determined whether LBC specimens can be used for epidermal growth factor receptor (EGFR) mutation analysis in human lung adenocarcinoma cell lines.

Methods

Genomic DNA was extracted from 3 lung adenocarcinoma cell lines that were fixed in LBC preservation solution using 2 protocols (one for cultured cells and one for tissues) of a DNA extraction kit. Different fixation times were tested for each protocol: 30 minutes, 1 hour, and 1 to 9 days. As controls, cells also were fixed in 10% formalin or 95% ethanol. The authors investigated the effect of fixation time on DNA fragmentation, polymerase chain reaction (PCR) amplification, and EGFR mutation detection.

Results

The DNA yield of LBC specimens tended to decrease depending on fixation time. When using the DNA extraction protocol for tissues, PCR amplification was successful after 9 days of fixation, although extracted genomic DNA that was fixed for >1 hour demonstrated fragmentation. Mutation analyses using the Cycleave PCR method were successful after 7 days of fixation. The DNA extraction protocol for tissues was appropriate for lung adenocarcinoma cell lines that were stored for >1 day in a preservative solution. The results of the current study demonstrated that EGFR mutations can be detected on day 7 using lung adenocarcinoma cell lines fixed in CytoRich Red preservative.

Conclusions

When LBC specimens are used for targeted molecular genetic testing, the appropriate preservative solution and extraction protocol first should be determined.
Two‐photon fluorescence lifetime imaging of intrinsic NADH in three‐dimensional tumor models
Authors: Cong Anh , Pimenta Rafaela M. L. , Lee Hong Bok , Mereddy Venkatram , Holy Jon , Heikal Ahmed A.
Published: October 2018

Most studies using intrinsic NAD(P)H as biomarkers for energy metabolism and mitochondrial anomalies have been conducted in routine two‐dimensional (2D) cell culture formats. Cellular metabolism and cell behavior, however, can be significantly different in 2D cultures from that in vivo. As a result, there are emerging interests in integrating noninvasive, quantitative imaging techniques of NAD(P)H with in vivo‐like three‐dimensional (3D) models. The overall features and metabolic responses of the murine breast cancer cells line 4T1 in 2D cultures were compared with those in 3D collagen matrix using integrated optical micro‐spectroscopy. The metabolic responses to two novel compounds, MD1 and TPPBr, that target metabolism by disrupting monocarboxylate transporters or oxidative phosphorylation (OXPHOS), respectively, were investigated using two‐photon fluorescence lifetime imaging microscopy (2P‐FLIM) of intracellular NAD(P)H in 2D and 3D cultures. 4T1 cells exhibit distinct behaviors in a collagenous 3D matrix from those in 2D culture, forming anastomosing multicellular networks and spherical acini in 3D culture, as opposed to simple flattened epithelial plaques in 2D culture. The cellular NAD(P)H in 3D collagen matrix exhibits a longer fluorescence lifetime as compared with 2D culture, which is attributed to an enhanced population of enzyme‐bound NAD(P)H in the 3D culture. TPPBr induces mitochondrial hyperpolarization in 2D culture of 4T1 cells along with an enhanced free NAD(P)H population, which suggest an interference with OXPHOS. In contrast, 2P‐FLIM of cellular NAD(P)H revealed an enhanced autofluorescence lifetime in 3D 4T1 cultures after MD1 treatment as compared with MD1‐treated 2D culture and the control 3D culture. Physical and chemical microenvironmental signaling are critical factors in understanding how therapeutic compounds target cancer cells by disrupting their metabolic pathways. Integrating 2P‐FLIM of intrinsic NAD(P)H with refined 3D tumor‐matrix in vitro models promises to advance our understanding of the roles of metabolism and metabolic plasticity in tumor growth and metastatic behavior. © 2018 International Society for Advancement of Cytometry
Is routine ECC necessary in patients with HPV16 and normal cytology?
Authors: Ureyen Isin , Toptas Tayfun , Uysal Aysel
Published: October 2018

Background

In the present study, we primarily aimed to correlate the colposcopy results of patients with human papillomavirus (HPV) positivity and abnormal cervical screening results. Secondarily, we attempted to define the role of endocervical curettage (ECC) in the colposcopic evaluation of patients who had normal cytology and HPV16, which is the most carcinogenic HPV type.

Methods

This was a retrospective study analyzing the data of patients who had colposcopies between January 2015 and May 2016 in the Gynecological Oncology clinic of a single tertiary center. The data were evaluated to identify the pathologies in patients with HPV positivity and abnormal cervical screening results. A Colposcopic examination database was evaluated to obtain information regarding the cervical transformation zone (TZ), which was divided into three types by the International Federation for Cervical Pathology and Colposcopy. The binary variables were reported as counts and percentages.

Results

A total of 1049 patients were included in the analysis. The median age of the patients was 43 (range: 21‐79). Cervical biopsies, ECC results, or both revealed cervical intraepithelial neoplasia 2+ (CIN2+: CIN2, CIN3, and invasive cancer) lesions in 22% (70/322) of the patients with HPV16 positivity, while this ratio was 8% (6/78) for patients with HPV18. CIN2+ lesions were detected in the 2.5% of patients with HPV positivity for types other than 16 and 18, as well as normal cytology. In the group of patients with HPV 16 and normal cytology, CIN2+ results were observed in the ECC of 11% of the patients whose colposcopy was normal regardless of the TZ type. Ten of the patients had invasive cancer.

Conclusion

The current study provides evidence for the possible role of routine ECC in patients with HPV16, normal cytology, and a normal colposcopy.
Thiazole‐substituted benzoylpiperazine derivatives as acetylcholinesterase inhibitors
Authors: Sahin Zafer , Ertas Merve , Bender Ceysu , Bülbül Emre F. , Berk Barkin , Biltekin Sevde N. , Yurttaş Leyla , Demirayak Şeref
Published: October 2018

Hit, Lead & Candidate Discovery

After acetylcholine is released into the synaptic cleft, it is reabsorbed or deactivated by acetylcholinesterase (AChE). Studies on Alzheimer's disease (AD) in the mid‐20th century proved that cognitive dysfunctions are associated with cholinergic neurotransmission. Drugs, such as tacrine, rivastigmine, donepezil, and galantamine are known as acetylcholinesterase inhibitors. However, these drugs have limited use in advanced AD and dementia. Recently, the anticholinesterase activity of various heterocyclic‐framed compounds, including piperazine derivatives, has been investigated, and compounds with similar effects to known drugs have been identified. The aim of this study was to design new donepezil analogs.

In this study, 66 original piperazinyl thiazole derivatives were synthesized by the reaction of piperazine N′‐benzoyl thioamides and bromoacetophenones to inhibit AChE. Biological activity was measured by the Ellman method. Compounds 35, 38, 40, 45, 57, and 61 showed a high inhibitory effect among the series (80.36%–83.94% inhibition), and donepezil had a 96.42% inhibitory effect. The IC50 values of compounds 35, 38, and 40, were calculated as 0.9767 μM, 0.9493 μM, and 0.8023 μM, respectively. Compound 45 (IC50 = 1.122), Compound 57 (IC50 = 1.2130) and 61 (IC50 = 0.9193) also exhibited good activity on AChE. Molecular modeling studies were in agreement with the predictions. Trp286, Arg296, and Tyr341 were the key amino acids at the active site. Both donepezil and synthesized compounds seemed to interact with these residues.
Ionic Liquids as Environmentally Benign Electrolytes for High‐Performance Supercapacitors
Authors: Shahzad Suniya , Shah Afzal , Kowsari Elaheh , Iftikhar Faiza Jan , Nawab Anum , Piro Benoit , Akhter Mohammad Salim , Rana Usman Ali , Zou Yongjin
Published: October 2018

Electrochemical capacitors (ECs) are a vital class of electrical energy storage (EES) devices that display the capacity of rapid charging and provide high power density. In the current era, interest in using ionic liquids (ILs) in high‐performance EES devices has grown exponentially, as this novel versatile electrolyte media is associated with high thermal stability, excellent ionic conductivity, and the capability to withstand high voltages without undergoing decomposition. ILs are therefore potentially useful materials for improving the energy/power performances of ECs without compromising on safety, cyclic stability, and power density. The current review article underscores the importance of ILs as sustainable and high‐performance electrolytes for electrochemical capacitors.
The association of puerperal sepsis with HIV infection at two tertiary hospitals in Zimbabwe
Authors: Majangara Rumbidzai , Chirenje Zvavahera M. , Gidiri Muchabaiwa F.
Published: October 2018

Objective

To evaluate the association between HIV infection and puerperal sepsis among women in Zimbabwe.

Methods

A subanalysis was performed using data from a prospective cohort study conducted between September 2, 2014, and July 1, 2015, at two tertiary hospitals in Zimbabwe. Eligible participants were consecutive women who met the WHO criteria for puerperal sepsis. Variables assessed included HIV‐infection status and the use of antiretroviral therapy. Severity of immunosuppression was defined by the number of T cells that expressed cluster of differentiation 4 (CD4). Endocervical swabs and blood samples were collected for microbial culture and susceptibility testing.

Results

In all, 33 (21.9%) of the 151 women included in the present analysis had HIV. Among women with HIV, severe immunosuppression (CD4‐positive T cell count <200/mm3) was associated with a mean hospital stay of 19.0 days versus 10.2 days for mild‐advanced immunosuppression (CD4‐positive T cell count 200–500/mm3) and insignificant immunosuppression (CD4‐positive T cell count >500/mm3; P=0.030). Use of antiretroviral therapy did not independently influence clinical outcomes. Furthermore, infection with HIV did not influence the microorganisms isolated from blood or endocervical samples.

Conclusion

Severe immunosuppression was associated with increased length of hospitalization among women with HIV who had puerperal sepsis.
Structural VARs and noninvertible macroeconomic models
Authors: Forni Mario , Gambetti Luca , Sala Luca
Published: October 2018

We resume the line of research pioneered by C. A. Sims and Zha (Macroeconomic Dynamics, 2006, 10, 231–272) and make two novel contributions. First, we provide a formal treatment of partial fundamentalness—that is, the idea that a structural vector autoregression (VAR) can recover, either exactly or with good approximation, a single shock or a subset of shocks, even when the underlying model is nonfundamental. In particular, we extend the measure of partial fundamentalness proposed by Sims and Zha to the finite‐order case and study the implications of partial fundamentalness for impulse‐response and variance‐decomposition analysis. Second, we present an application where we validate a theory of news shocks and find it to be in line with the empirical evidence.
Testing the limits of behavior analysis: A review of Frans de Waal'sAre we smart enough to know how smart animals are?
Authors: Leslie Julian C.
Published: October 2018

In “Are we smart enough to know how smart animals are?” de Waal (2016) summarizes field studies and experiments that demonstrate a huge number of examples of complex behavior in many animal species. His avowed aim is to challenge the views of both lay people and scientists about the limits of intelligence of other species and to demonstrate much closer similarity in the achievements of other species to those of humans, thus undermining claims of human uniqueness. His general explanatory scheme is to infer human‐like cognitive processes in other species to explain complex behavior, at least when this is supported by other evolutionary considerations. This review suggests how behavior analysis might explain some of the phenomena outlined by de Waal, indicates where its explanatory system may need to expand and develop to encompass a wider range of behavior, and points to similarities as well as differences between the explanatory scheme used by de Waal and that of behavior analysis.
Targeting metabolic pathways proteins of Orientia tsutsugamushi using combined hierarchical approach to combat scrub typhus
Authors: Sharma Dixit , Sharma Ankita , Verma Shailender Kumar , Singh Birbal
Published: October 2018

Orientia tsutsugamushi (Ott)is a causative agent of chigger‐borne zoonosis, scrub typhus which is life threatening and highly pervasive illness in humans. In this report, we have mined and classified the proteins involved in pathways unique toOttby using high‐throughput computational techniques. The 12 metabolic pathways were found to be unique to the pathogen. Forty‐six proteins were reported to be essential for the pathogen's survival and non‐homologous to the humans. The proteins were categorized into different classes, ie, enzymes, transporters, DNA‐binding, secretory, and outer membrane proteins. Further,in silicoanalysis of 46 proteins showed that 25 proteins were suitable therapeutic targets with known druggable properties. The structural modeling of B3CSG3 (MurA) protein was carried out and catalytic site essential for its functioning was analyzed. Virtual screening of chemical compounds was performed against modeled structure. The docking study by AutodockVina reported compound from PubChem with CID: 16036947 as best and potential inhibitor by means of docking score and binding affinity. The reliability and stability of the MurA‐16036947 complex were confirmed with molecular dynamics simulation. The report will provide insight to understand the mechanism of pathogenesis ofOttand instigate the development of effective treatment strategies against this disease.
Improving Hepatocyte Engraftment Following Hepatocyte Transplantation Using Repeated Reversible Portal Vein Embolization in Rats
Authors: Gaillard Martin , Tranchart Hadrien , Lainas Panagiotis , Trassard Olivier , Remy Séverine , Dubart‐Kupperschmitt Anne , Dagher Ibrahim
Published: October 2018

Hepatocyte transplantation (HT) has emerged as a promising alternative to orthotopic liver transplantation, yet liver preconditioning is needed to promote hepatocyte engraftment. A method of temporary occlusion of the portal flow called reversible portal vein embolization (RPVE) has been demonstrated to be an efficient method of liver preconditioning. By providing an additional regenerative stimulus, repeated reversible portal vein embolization (RRPVE) could further boost liver engraftment. The aim of this study was to determine the efficiency of liver engraftment of transplanted hepatocytes after RPVE and RRPVE in a rat model. Green fluorescent protein–expressing hepatocytes were isolated from transgenic rats and transplanted into 3 groups of syngeneic recipient rats. HT was associated with RPVE in group 1, with RRPVE in group 2, and with sham embolization in the sham group. Liver engraftment was assessed at day 28 after HT on liver samples after immunostaining. Procedures were well tolerated in all groups. RRPVE resulted in increased engraftment rate in total liver parenchyma compared with RPVE (3.4% ± 0.81% versus 1.4% ± 0.34%; P < 0.001). In conclusion, RRPVE successfully enhanced hepatocyte engraftment after HT and could be helpful in the frame of failure of HT due to low cell engraftment.
Marijuana medusa: The many pulmonary faces of marijuana inhalation in adolescent males
Authors: McGraw Matthew D. , Houser Grace H. , Galambos Csaba , Wartchow Eric P. , Stillwell Paul C. , Weinman Jason P.
Published: October 2018

Marijuana use has risen dramatically over the past decade. Over this same time period, pediatric hospitals have seen an increase in presentation of adolescents with acute respiratory symptoms after recent marijuana inhalation. We report a case series of three adolescent males with significant findings of bilateral pulmonary nodules and ground glass opacities on chest imaging associated with recent marijuana inhalation. Lung biopsies in two of the three patients confirmed silica‐induced pneumoconiosis. The third patient was diagnosed with acute hypersensitivity pneumonitis without lung biopsy. Improvement in clinical symptoms and lung function testing were noted in two of three patients after marijuana inhalation cessation. This case series highlights the variety of severe pulmonary presentations in adolescents following recent marijuana inhalation. Future studies are required to assess whether these presenting pulmonary complications are from direct marijuana exposure or indirect associations with marijuana inhalation injuries.
Pharmacokinetic‐Pharmacodynamic Model of Neutropenia in Patients With Myeloma Receiving High‐Dose Melphalan for Autologous Stem Cell Transplant
Authors: Cho Yu Kyoung , Irby Donald J. , Li Junan , Sborov Douglas W. , Mould Diane R. , Badawi Mohamed , Dauki Anees , Lamprecht Misty , Rosko Ashley E. , Fernandez Soledad , Hade Erinn M. , Hofmeister Craig C. , Poi Ming , Phelps Mitch A.
Published: October 2018

High‐dose melphalan (HDM) is part of the conditioning regimen in patients with multiple myeloma (MM) receiving autologous stem cell transplantation (ASCT). However, individual sensitivity to melphalan varies, and many patients experience severe toxicities. Prolonged severe neutropenia is one of the most severe toxicities and contributes to potentially life‐threatening infections and failure of ASCT. Granulocyte‐colony stimulating factor (G‐CSF) is given to stimulate neutrophil proliferation after melphalan administration. The aim of this study was to develop a population pharmacokinetic/pharmacodynamic (PK/PD) model capable of predicting neutrophil kinetics in individual patients with MM undergoing ASCT with high‐dose melphalan and G‐CSF administration. The extended PK/PD model incorporated several covariates, including G‐CSF regimen, stem cell dose, hematocrit, sex, creatinine clearance, p53 fold change, and race. The resulting model explained portions of interindividual variability in melphalan exposure, therapeutic effect, and feedback regulation of G‐CSF on neutrophils, thus enabling simulation of various doses and prediction of neutropenia duration.
Monochromatic cycle covers in random graphs
Authors: Korándi Dániel , Mousset Frank , Nenadov Rajko , Škorić Nemanja , Sudakov Benny
Published: October 2018

A classic result of Erdős, Gyárfás and Pyber states that for every coloring of the edges of Kn with r colors, there is a cover of its vertex set by at most vertex‐disjoint monochromatic cycles. In particular, the minimum number of such covering cycles does not depend on the size of Kn but only on the number of colors. We initiate the study of this phenomenon in the case where Kn is replaced by the random graph . Given a fixed integer r and , we show that with high probability the random graph has the property that for every r‐coloring of the edges of G, there is a collection of monochromatic cycles covering all the vertices of G. Our bound on p is close to optimal in the following sense: if , then with high probability there are colorings of such that the number of monochromatic cycles needed to cover all vertices of G grows with n.
Probabilistic consequences of some polynomial recurrences
Authors: Hitczenko Paweł , Lohss Amanda
Published: October 2018

In this paper, we consider sequences of polynomials that satisfy certain recurrences. Our interest is motivated by the fact that polynomials satisfying such recurrences frequently appear as generating polynomials of integer valued random variables that are of interest in discrete mathematics. In particular, we will use our approach to show that the number of diagonal boxes in symmetric tree‐like tableaux is asymptotically normal. This extends earlier results of Aval, Boussicault and Nadeau, who found the asymptotics of the expected number of diagonal boxes. Through our discussion, we establish a general framework to approach such recurrences and prompt a generalization of the probabilistic consequences of them.