bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Biopsy Technique on Molecular Genetic Tumor Characterization in Non-Small Cell Lung Cancer—The Prospective, Randomized, Single-Blinded, Multicenter PROFILER Study Protocol
Authors: Haentschel Maik , Boeckeler Michael , Bonzheim Irina , Schimmele Florian , Spengler Werner , Stanzel Franz , Petermann Christoph , Darwiche Kaid , Hagmeyer Lars , Buettner Reinhard , Tiemann Markus , Schildhaus Hans-Ulrich , Muche Rainer , Boesmueller Hans , Everinghoff Felix , Mueller Robert , Atique Bijoy , Lewis Richard A. , Zender Lars , Fend Falko , Hetzel Juergen
Published: July 2020

The detection of molecular alterations is crucial for the individualized treatment of advanced non-small cell lung cancer (NSCLC). Missing targetable alterations may have a major impact on patient’s progression free and overall survival. Although laboratory testing for molecular alterations has continued to improve; little is known about how biopsy technique affects the detection rate of different mutations. In the retrospective study detection rate of epidermal growth factor (EGFR) mutations in tissue extracted by bronchoscopic cryobiopsy (CB was significantly higher compared to other standard biopsy techniques. This prospective, randomized, multicenter, single blinded study evaluates the accuracy of molecular genetic characterization of NSCLC for different cell sampling techniques. Key inclusion criteria are suspected lung cancer or the suspected relapse of known NSCLC that is bronchoscopically visible. Patients will be randomized, either to have a CB or a bronchoscopic forceps biopsy (FB). If indicated, a transbronchial needle aspiration (TBNA) of suspect lymph nodes will be performed. Blood liquid biopsy will be taken before tissue biopsy. The primary endpoint is the detection rate of molecular genetic alterations in NSCLC, using CB and FB. Secondary endpoints are differences in the combined detection of molecular genetic alterations between FB and CB, TBNA and liquid biopsy. This trial plans to recruit 540 patients, with 178 evaluable patients per study cohort. A histopathological and molecular genetic evaluation will be performed by the affiliated pathology departments of the national network for genomic medicine in lung cancer (nNGM), Germany. We will compare the diagnostic value of solid tumor tissue, lymph node cells and liquid biopsy for the molecular genetic characterization of NSCLC. This reflects a real world clinical setting, with potential direct impact on both treatment and survival.
Diagnostic Roles of Immunohistochemistry in Thymic Tumors: Differentiation between Thymic Carcinoma and Thymoma
Authors: Jeong Jae-Han , Pyo Jung-Soo , Kim Nae-Yu , Kang Dong-Wook
Published: July 2020

Background: The present study aims to evaluate the diagnostic roles of various immunohistochemical (IHC) markers in thymic tumors, including thymic carcinoma (TC) and thymoma (TM). Methods: Eligible studies were obtained by searching the PubMed databases and screening the searched articles. Thirty-eight articles were used in the present meta-analysis and included 636 TCs and 1861 TMs. Besides, for IHC markers with statistical significance, a diagnostic test accuracy review was performed. Results: The comparison of various IHC expressions between TC and TM was performed for 32 IHC markers. Among these IHC markers, there were significant differences between TC and TM for beta-5t, B-cell lymphoma 2 (Bcl-2), calretinin, CD1a, CD5, carcinoembryonic antigen (CEA), cytokeratin19 (CK19), CD117, glucose transporter 1 (Glut-1), insulin-like growth factor 1 receptor (IGF-1R), mesothelin, MOC31, mucin1 (MUC1), p21, and terminal deoxynucleotidyl transferase (TdT). Markers with higher expressions in TCs were Bcl-2, calretinin, CD5, CEA, CD117, Glut-1, IGF-1R, mesothelin, MOC31, MUC1, and p21. Among these markers, there were no significant differences between TC and TM type B3 in immunohistochemistries for Bcl-2 and CK19. On the other hand, β-catenin and CD205 showed a considerable difference in IHC expressions between TC and TM type B3, but not between TC and overall TM. In diagnostic test accuracy review, MUC1 and beta-5t were the most useful markers for TC and TM, respectively. Conclusions: Taken together, our results showed that the expression rates for various IHC markers significantly differed between TC and TM. The IHC panel can be useful for differentiation from limited biopsied specimens in daily practice.
Dental Students’ Perceptions before and after Attending a Centre for Children with Special Needs: A Qualitative Study on Situated Learning
Authors: Fadel Hani T. , Baghlaf Khlood , Ben Gassem Afnan , Bakeer Hala , Alsharif Alla T. , Kassim Saba
Published: July 2020

Objectives: To develop an in-depth understanding of the perceptions and experiences of senior dental students before and after fieldwork visits to a centre for children with special needs. Methods: A qualitative study utilised open-ended questions and involved 39 fifth-year dental students. A thematic analysis of the collected responses was undertaken, and a hierarchy of themes and subthemes were developed. Results: Analysis of the pre-visit responses revealed three main themes and a number of subthemes: ‘negative expectations’, ‘positive expectations’, and ‘pain expectations’. Similarly, four main themes with a number of subthemes emerged from the post-visit responses: ‘positive perceptions’, ‘negative perceptions’, ‘oral problems observed’, and ‘recommendations’. Conclusions: Within the study limits, different perspectives were extracted. Prior to the fieldwork visit, students expressed their lack of self-confidence and inadequate preparation. Following the situated learning visit experience, students’ perceptions of managing special needs children was positively influenced. Students were happy to be exposed to such an experience, but hoped for better organisation and specialised supervision in the future.
Trade-Offs in Competitive Transport Operations
Authors: Akbar Usman , Kumar Akash , Khan Hameed , Khan Muhammad Asif , Parvaiz Khansa , Oláh Judit
Published: July 2020

One of the goals of developing a transport corridor is to promote socio-economic development by improving connectivity and sustainable transport operations, which largely depends on the operational strategy. Trade-off policies can be important tools for gaining the competitive advantage of road transport corridors, and thus, help facilitate sustainable growth and welfare. This article uses a case-based approach to observe the trade-offs in the first phase of transport infrastructure development, and then, in the second stage, further explores the trade-off variables in the transport operations strategy under the China-Pakistan Economic Corridor (CPEC). The results from the three cases of the parallel route system of the CPEC indicate that trade-off is an easily understandable and applicable method, which can foresee the operational gains or compromises for significant welfare of the regions. The implications of the trade-off are two fold, first is the “importance” of the trade-off, which is related to its impact on operational competitiveness. The other is the “sensitivity” of the trade-off, in terms of the change that will be caused to one variable when changing the other. The trade-off concept can be used for several landlocked transport corridors to achieve a competitive edge in transit trade.
A SVM-3D Based Encoderless Control of a Fault-Tolerant PMSM Drive
Authors: Saleh Kamel , Sumner Mark
Published: July 2020

This paper exhibits a novel technique to obtain an encoderless speed control of a permanent magnet synchronous motor (PMSM) in the case of a loss of one phase. The importance of this work is that it presents solutions in order to maintain the operation of the system in various conditions. This will increase the reliability of the whole drive system to meet the safety issues required in some applications. To achieve that, a fault-tolerant inverter modulated through a 3-dimension space vector pulse width modulation technique (3D-SVPWM) is used. Besides that, an algorithm to obtain the exact position of the saturation saliency in the case of a loss of one phase is introduced to achieve a closed-loop field-oriented encoderless speed control and to further enhance the reliability of the whole drive system. This algorithm is based on measuring the transient stator current responses of the motor due to the insulated-gate bipolar transistors (IGBTs) switching actions. Then according to the operating condition (normal or a loss of one phase), the saliency position signals are constructed from the dynamic current responses. Simulation results are provided to demonstrate the effectiveness of the saliency tracking technique under normal and under a loss of one phase conditions. Moreover, the results verify the maximum reliability for the whole drive system that is achieved in this work through a continuous operation of the drive system under a loss of one phase condition and under encoderless speed control.
Efficient Estimator of Rotor Temperature Designing for Electric and Hybrid Powertrain Platform
Authors: Tran Tuan-Vu , Nègre Edouard
Published: July 2020

This paper presents an efficient method of estimation of rotor cage temperature for induction machine design, applied for electric and hybrid vehicles. This factor influences the torque produced by the induction machine with a field-oriented control algorithm. Equipping sensors to measure the temperature of a rotation component is expensive and is not representative of mass production. The approach of estimation of rotor cage temperature is based on the good knowledge of motor parameters and the estimation of the flux of the machine. For an accuracy inductance taking account of the saturation, the no-load test can be performed. The machine flux will be estimated taking account of the voltage drop of the system on the test-bench. The rapid prototyping in a real-time motor control platform will be presented that integrates this estimator of rotor temperature. We finally show the experimental testing results compared to the measurement of the rotor cage on a prototype asynchronous low-cost motor designing for battery electric city cars.
TagML—An Implementation Specific Model to Generate Tag-Based Documents
Authors: Tesoriero Ricardo , Sebastian Gabriel , Gallud Jose A.
Published: July 2020

This article describes TagML, a method to generate collections of XML documents using model-to-model (M2M) transformations. To accomplish this goal, we define the TagML meta-model and the TagML-to-XML model-to-text transformation. While TagML models represent the essential characteristics of collections of XML documents, the TagML-to-XML transformation generates the textual representation of collections of XML documents from TagML models. This approach enables developers to define model-to-model transformations to generate TagML models. These models are turned into text applying the TagML-to-XML transformation. Consequently, developers are able to use declarative languages to define model-to-text transformations that generate XML documents, instead of traditional archetype-based languages to define model-to-text transformations that generate collections of XML documents. The TagML model editor as well as the TagML-to-XML transformation were developed as Eclipse plugins using the Eclipse Modeling Framework. The plugin has been developed following the Object Modeling Group standards to ensure the compatibility with legacy tools. Using TagML, unlike other previous proposals, implies the use of model-to-model transformations to generate XML documents, instead of model-to-text transformations, which results on an improvement of the transformation readability and reliability, as well as a reduction of the transformation maintenance costs. The proposed approach helps developers to define transformations less prone to errors than using the traditional approach. The novelty of this approach is based on the way XML documents are generated using model-to-model transformations instead of traditional model-to-text transformations. Moreover, the simplicity of the proposed approach enables the generation of XML documents without the need for any transformation configuration, which does not penalize the model reuse. To illustrate the features of the proposal, we present the generation of XHTML documents using UML class diagrams as input models. The evaluation section demonstrates that the proposed method is less prone to errors than the traditional one.
Policy Responses to Direct and Underlying Drivers of Deforestation: Examining Rubber and Coffee in the Central Highlands of Vietnam
Authors: Kissinger Gabrielle
Published: July 2020

Viet Nam’s Central Highlands are a priority region for its National REDD+ Action Plan (NRAP) to reduce emissions from deforestation and forest degradation but are under strong pressures from rubber and coffee production and expansion into forests, and future climate stress. This research explores to what extent REDD+ and sectoral policy interventions have addressed both the direct and underlying drivers of deforestation and forest degradation in this region, with particular focus on the actors and scales that policy interventions must reach to affect driver pressure. National-level policy responses to driver pressures are assessed, with the results indicating poor correlations between the direct drivers and related underlying drivers. The research proposes a framework to guide the policy design and evaluation of response options to enable identification of the causal connections between direct and underlying drivers, and consider future pressures, which actors to target (or not miss) and which scales are best suited for interventions (from international to national, sub-national and local). This is highly relevant for countries pursuing forest and land use sector solutions through Nationally Determined Contributions to the Paris Agreement and REDD+.
Plus Tree Selection of Quercus salicina Blume and Q. glauca Thunb. and Its Implications in Evergreen Oaks Breeding in Korea
Authors: Kim In Sik , Lee Kyung Mi , Shim Donghwan , Kim Jin Jung , Kang Hye-In
Published: July 2020

This study was conducted to select plus trees of two evergreen oaks, Quercus salicina and Q. glauca, in Korea. Evergreen oaks are distributed in subtropical region in Korea and have recently emerged as one of the alternative tree species against climate change. Accordingly, a tree breeding program is underway to foster evergreen oaks as a reforestation species for the future. Through intensive survey on the distribution range, 15 stands (8 for Q. salicina, 3 for Q. glauca, and 4 for both species) were selected as base populations. To select candidate trees, we developed a subjective grading system with six characteristics in three categories and introduced a weighted generalized value (GVIw) to compare superiority of candidate trees. The candidate trees were screened using baseline value ‘0’, i.e., if GVIw > 0, then accepted and if GVIw < 0, then rejected. After then, adjustment was conducted to avoid biasing the selection of plus trees for a particular location. Through this process, 44 candidate trees in Q. salicina and 41 candidate trees in Q. glauca were selected as plus trees. Finally, the results and implications were discussed in relation to evergreen oak breeding in Korea.
Biogeographic, Atmospheric, and Climatic Factors Influencing Tree Growth in Mediterranean Aleppo Pine Forests
Authors: Camarero J. , Sánchez-Salguero Raúl , Ribas Montserrat , Touchan Ramzi , Andreu-Hayles Laia , Dorado-Liñán Isabel , Meko David , Gutiérrez Emilia
Published: July 2020

There is a lack of knowledge on how tree species respond to climatic constraints like water shortages and related atmospheric patterns across broad spatial and temporal scales. These assessments are needed to project which populations will better tolerate or respond to global warming across the tree species distribution range. Warmer and drier conditions have been forecasted for the Mediterranean Basin, where Aleppo pine (Pinus halepensis Mill.) is the most widely distributed conifer in dry sites. This species shows plastic growth responses to climate, being particularly sensitive to drought. We evaluated how 32 Aleppo pine forests responded to climate during the second half of the 20th century by using dendrochronology. Climatic constraints of radial growth were inferred by fitting the Vaganov–Shashkin (VS-Lite) growth model to ring-width data from our Aleppo pine forest network. Our findings reported that Aleppo pine growth decreased and showed the highest common coherence among trees in dry, continental sites located in southeastern and eastern inland Spain and Algeria. In contrast, growth increased in wetter sites located in northeastern Spain. Overall, across the Aleppo pine network tree growth was enhanced by prior wet winters and cool and wet springs, whilst warm summers were associated with less growth. The relationships between site ring-width chronologies were higher in nearby forests. This explains why Aleppo pine growth was distinctly linked to indices of atmospheric circulation patterns depending on the geographical location of the forests. The western forests were more influenced by moisture and temperature conditions driven by the Western Mediterranean Oscillation (WeMO) and the Northern Atlantic Oscillation (NAO), the southern forests by the East Atlantic (EA) and the august NAO, while the Balearic, Tunisian and northeastern sites by the Arctic Oscillation (AO) and the Scandinavian pattern (SCA). The climatic constraints for Aleppo pine tree growth and its biogeographical variability were well captured by the VS-Lite model. The model performed better in dry and continental sites, showing strong growth coherence between trees and climatic limitations of growth. Further research using similar broad-scale approaches to climate–growth relationships in drought-prone regions deserves more attention.
Enhancement of Immune Activities of Mixtures with Sasa quelpaertensis Nakai and Ficus erecta var. sieboldii
Authors: Kwon Hee-Yeon , Choi Sun-Il , Han Xionggao , Men Xiao , Jang Gill-Woong , Choi Ye-Eun , Kim Seung-Hyung , Kang Jun-Chul , Cho Ju-Hyun , Lee Ok-Hwan
Published: July 2020

The objective of the present study was to develop a concoction of natural products that could dramatically improve immune function with minimal possible side effects. Sasa quelpaertensis Nakai and Ficus erecta var. sieboldii are plants that are native to Jeju Island, Korea and are known to be rich in physiologically active substances. We prepared a mixture of different proportions and extraction conditions using two natural plants and determined their optimum mixing ratio and extraction method by assessing immune function-related biomarkers in RAW264.7 macrophages. Optimal extract (HR02/04(8:2)-W) was selected from in vitro experiments and its immunity-enhancing efficacy was evaluated in mice. After oral administration of extract to BALB/c mice for 2 weeks, nitric oxide production in the peritoneal exudate cells, natural killer cell cytotoxicity, cytokine expression in splenocytes, and total cell number of immune tissues and phenotype analysis were evaluated. Our results demonstrated that HR02/04(8:2)-W significantly enhanced the immune system by increasing natural killer cell activity, cytokine expression, and total number of cells in immune tissues. In conclusion, our study validates the role of HR02/04(8:2)-W in enhancing immunity and its potential development as a functional food.
Spray-Drying Microencapsulation of High Concentration of Bioactive Compounds Fragments from Euphorbia hirta L. Extract and Their Effect on Diabetes Mellitus
Authors: Tran Ngan , Tran Minh , Truong Han , Le Ly
Published: July 2020

The present study was performed to spray-dry the high concentration of bioactive compounds from Euphorbia hirta L. extracts that have antidiabetic activity. The total phenolic content (TPC) and total flavonoid content (TFC) of four different extracts (crude extract, petroleum ether extract, chloroform extract and ethyl acetate extract) from the dried powder of Euphorbia hirta L. were determined using a spectrophotometer. After that, the fragment containing a high number of bioactive compounds underwent spray-dried microencapsulation to produce powder which had antidiabetic potential. The total phenolic content values of the crude extract, petroleum ether extract, chloroform extract and ethyl acetate extract were 194.55 ± 0.82, 51.85 ± 3.12, 81.56 ± 1.72 and 214.21 ± 2.53 mg/g extract, expressed as gallic acid equivalents. Crude extract, petroleum ether extract, chloroform extract and ethyl acetate extracts showed total flavonoids 40.56 ± 7.27, 29.49 ± 1.66, 64.99 ± 2.60 and 91.69 ± 1.67 mg/g extract, as rutin equivalents. Ethyl acetate extract was mixed with 20% maltodextrin in a ratio of 1:10 to spray-dry microencapsulation. The results revealed that the moisture content, bulk density, color characteristic, solubility and hygroscopicity of the samples were 4.9567 ± 0.00577%, 0.3715 ± 0.01286 g/mL, 3.7367 ± 0.1424 Hue, 95.83 ± 1.44% and 9.9890 ± 1.4538 g H2O/100 g, respectively. The spray powder was inhibited 51.19% α-amylase at 10 mg/mL and reduced 51% in fast blood glucose (FBG) after 4 h treatment. Furthermore, the administration of spray powder for 15 days significantly lowered the fast blood glucose level in streptozotocin-diabetic mice by 23.32%, whereas, acarbose—a standard antidiabetic drug—and distilled water reduced the fast blood glucose level by 30.87% and 16.89%. Our results show that obtained Euphorbia hirta L. powder has potential antidiabetic activity.
Determination of Organosulfides from Onion Oil
Authors: Cantrell Maranda S. , Seale Jared T. , Arispe Sergio A. , McDougal Owen M.
Published: July 2020

Qualitative and semi-quantitative analysis of organosulfides extracted from oil obtained by steam distillation of yellow onions was performed by gas chromatography-mass spectrometry (GC-MS). The extraction efficiency of organosulfides from onion oil was evaluated across four solvents: dichloromethane; diethyl ether; n-pentane; and hexanes. Analysis of solvent extracted organosulfides by GC-MS provided qualitative results that support the use of dichloromethane over other solvents based on identification of 27 organosulfides from the dichloromethane extract as compared to 10 from diethyl ether; 19 from n-pentane; and 17 from hexanes. Semi-quantitative evaluation of organosulfides present in the dichloromethane extract was performed using diallyl disulfide as the internal reference standard. Three organosulfides were detected in the extract at ≥5 mg/kg; 18 organosulfides between 3–5 mg/kg; and six organosulfides at <3 mg/kg. The E/Z isomers of 1-propenyl propyl trisulfide were among the most prevalent components extracted from the onion oil across all solvents; and 3,6-diethyl-1,2,4,5-tetrathiane was among the most abundant organosulfides in all solvents except hexanes. The method described here for the extraction of organosulfides from steam distilled onion oil surveys common solvents to arrive at a qualitative and semi-quantitative method of analysis for agricultural products involving onions; onion oil; and secondary metabolites of Allium spp.
Rotational Disruption of Astrophysical Dust and Ice—Theory and Applications
Authors: Hoang Thiem
Published: July 2020

Dust is an essential component of the interstellar medium (ISM) and plays an important role in many different astrophysical processes and phenomena. Traditionally, dust grains are known to be destroyed by thermal sublimation, Coulomb explosions, sputtering, and shattering. The first two mechanisms arise from the interaction of dust with intense radiation fields and high-energy photons (extreme UV), which work in a limited astrophysical environment. The present review is focused on a new destruction mechanism present in the dust-radiation interaction that is effective in a wide range of radiation fields and has ubiquitous applications in astrophysics. We first describe this new mechanism of grain destruction, namely rotational disruption induced by Radiative Torques (RATs) or RAdiative Torque Disruption (RATD). We then discuss rotational disruption of nanoparticles by mechanical torques due to supersonic motion of grains relative to the ambient gas, which is termed MEchanical Torque Disruption (METD). These two new mechanisms modify properties of dust and ice (e.g., size distribution and mass), which affects observational properties, including dust extinction, thermal and nonthermal emission, and polarization. We present various applications of the RATD and METD mechanisms for different environments, including the ISM, star-forming regions, astrophysical transients, and surface astrochemistry.
Analysis of ACE2 Genetic Variability among Populations Highlights a Possible Link with COVID-19-Related Neurological Complications
Authors: Strafella Claudia , Caputo Valerio , Termine Andrea , Barati Shila , Gambardella Stefano , Borgiani Paola , Caltagirone Carlo , Novelli Giuseppe , Giardina Emiliano , Cascella Raffaella
Published: July 2020

Angiotensin-converting enzyme 2 (ACE2) has been recognized as the entry receptor of the novel severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). Structural and sequence variants in ACE2 gene may affect its expression in different tissues and determine a differential response to SARS-Cov-2 infection and the COVID-19-related phenotype. The present study investigated the genetic variability of ACE2 in terms of single nucleotide variants (SNVs), copy number variations (CNVs), and expression quantitative loci (eQTLs) in a cohort of 268 individuals representative of the general Italian population. The analysis identified five SNVs (rs35803318, rs41303171, rs774469453, rs773676270, and rs2285666) in the Italian cohort. Of them, rs35803318 and rs2285666 displayed a significant different frequency distribution in the Italian population with respect to worldwide population. The eQTLs analysis located in and targeting ACE2 revealed a high distribution of eQTL variants in different brain tissues, suggesting a possible link between ACE2 genetic variability and the neurological complications in patients with COVID-19. Further research is needed to clarify the possible relationship between ACE2 expression and the susceptibility to neurological complications in patients with COVID-19. In fact, patients at higher risk of neurological involvement may need different monitoring and treatment strategies in order to prevent severe, permanent brain injury.
Spatial and Temporal Dynamics of Contact Zones Between Chromosomal Races of House Mice, Mus musculus domesticus, on Madeira Island
Authors: Tapisso Joaquim T. , Gabriel Sofia I. , Cerveira Ana Mota , Britton-Davidian Janice , Ganem Guila , Searle Jeremy B. , Ramalhinho Maria da Graça , Mathias Maria da Luz
Published: July 2020

Analysis of contact zones between parapatric chromosomal races can help our understanding of chromosomal divergence and its influence on the speciation process. Monitoring the position and any movement of contact zones can allow particular insights. This study investigates the present (2012–2014) and past (1998–2002) distribution of two parapatric house mouse chromosomal races—PEDC (Estreito da Calheta) and PADC (Achadas da Cruz)—on Madeira Island, aiming to identify changes in the location and width of their contact. We also extended the 1998–2002 sampling area into the range of another chromosomal race—PLDB (Lugar de Baixo). Clinal analysis indicates no major geographic alterations in the distribution and chromosomal characteristics of the PEDC and PADC races but exhibited a significant shift in position of the Rb (7.15) fusion, resulting in the narrowing of the contact zone over a 10+ year period. We discuss how this long-lasting contact zone highlights the role of landscape on mouse movements, in turn influencing the chromosomal characteristics of populations. The expansion of the sampling area revealed new chromosomal features in the north and a new contact zone in the southern range involving the PEDC and PLDB races. We discuss how different interacting mechanisms (landscape resistance, behaviour, chromosomal incompatibilities, meiotic drive) may help to explain the pattern of chromosomal variation at these contacts between chromosomal races.
Detection of Multiple Transgene Fragments in a Mouse Model of Gene Doping Based on Plasmid Vector Using TaqMan-qPCR Assay
Authors: Sugasawa Takehito , Aoki Kai , Yanazawa Kouki , Takekoshi Kazuhiro
Published: July 2020

The World Anti-Doping Agency has prohibited gene doping in the context of progress in gene therapy. There is a risk that the augmentation of genes using plasmids could be applied for gene doping. However, no gold standard method to detect this has been established. Here, we aimed to develop a method to detect multiple transgene fragments as proof of gene doping. Firstly, gene delivery model mice as a mimic of gene doping were created by injecting firefly luciferase plasmid with polyethylenimine (PEI) into the abdominal cavity. The results confirmed successful establishment of the model, with sufficient luminescence upon in vivo imaging. Next, multiple transgene fragments in the model were detected in plasma cell-free (cf)DNA, blood-cell-fraction DNA, and stool DNA using the TaqMan- quantitative real-time PCR(qPCR) assay, with the highest levels in plasma cfDNA. Using just a single drop of whole blood from the model, we also attempted long-term detection. The results showed that multiple transgene fragments were detected until 11 days. These findings indicate that the combination of plasma cfDNA or just one drop of whole blood with TaqMan-qPCR assay is feasible to detect plasmid-PEI-based gene doping. Our findings could accelerate the development of methods for detecting gene doping in humans.
Prognostic Significance of RAS Mutations and P53 Expression in Cutaneous Squamous Cell Carcinomas
Authors: Campos Manuel António , Macedo Sofia , Fernandes Margarida Sá , Pestana Ana , Pardal Joana , Batista Rui , Vinagre João , Sanches Agostinho , Baptista Armando , Lopes José Manuel , Soares Paula
Published: July 2020

TP53 is considered the most commonly-altered gene in cutaneous squamous cell carcinoma (cSCC). Conversely, RAS mutations have been reported in a low percentage of cSCC. The objective of our study was to evaluate the frequency of p53 expression and RAS mutations in cSCC and correlate them with clinicopathological features and patient outcome. We performed immunohistochemistry for p53 and genetic profiling for RAS mutations in a retrospective series of cSCC. The predictive value of p53 expression, RAS mutations, and clinicopathological parameters was assessed using logistic regression models. The overall frequency of RAS mutations was 9.3% (15/162), and 82.1% of the cases (133/162) had p53 overexpression. RAS mutations rate was 3.2% (1/31) of in situ cSCCs and 10.7% (14/131) of invasive cSCCs. RAS mutations were more frequently associated with an infiltrative than an expansive pattern of invasion (p = 0.046). p53 overexpression was a predictor of recurrence in the univariate analysis. Our results indicate that RAS mutations associate with features of local aggressiveness. Larger studies with more recurrent and metastatic cSCCs are necessary to further address the prognostic significance of p53 overexpression in patients’ risk stratification.
The Importance of ATM and ATR in Physcomitrella patens DNA Damage Repair, Development, and Gene Targeting
Authors: Martens Martin , Horres Ralf , Wendeler Edelgard , Reiss Bernd
Published: July 2020

Coordinated by ataxia-telangiectasia-mutated (ATM) and ATM and Rad3-related (ATR), two highly conserved kinases, DNA damage repair ensures genome integrity and survival in all organisms. The Arabidopsis thaliana (A. thaliana) orthologues are well characterized and exhibit typical mammalian characteristics. We mutated the Physcomitrella patens (P. patens) PpATM and PpATR genes by deleting functionally important domains using gene targeting. Both mutants showed growth abnormalities, indicating that these genes, particularly PpATR, are important for normal vegetative development. ATR was also required for repair of both direct and replication-coupled double-strand breaks (DSBs) and dominated the transcriptional response to direct DSBs, whereas ATM was far less important, as shown by assays assessing resistance to DSB induction and SuperSAGE-based transcriptomics focused on DNA damage repair genes. These characteristics differed significantly from the A. thaliana genes but resembled those in yeast (Saccharomyces cerevisiae). PpATR was not important for gene targeting, pointing to differences in the regulation of gene targeting and direct DSB repair. Our analysis suggests that ATM and ATR functions can be substantially diverged between plants. The differences in ATM and ATR reflect the differences in DSB repair pathway choices between A. thaliana and P. patens, suggesting that they represent adaptations to different demands for the maintenance of genome stability.
Hybridization of Russian Sturgeon (Acipenser gueldenstaedtii, Brandt and Ratzeberg, 1833) and American Paddlefish (Polyodon spathula, Walbaum 1792) and Evaluation of Their Progeny
Authors: Káldy Jenő , Mozsár Attila , Fazekas Gyöngyvér , Farkas Móni , Fazekas Dorottya Lilla , Fazekas Georgina Lea , Goda Katalin , Gyöngy Zsuzsanna , Kovács Balázs , Semmens Kenneth , Bercsényi Miklós , Molnár Mariann , Patakiné Várkonyi Eszter
Published: July 2020

Two species from the families Acipenseridae and Polyodontidae, Russian sturgeon (Acipenser gueldenstaedtii, Brandt and Ratzeberg, 1833; functional tetraploid) and American paddlefish (Polyodon spathula, Walbaum 1792, functional diploid) were hybridized. The hybridization was repeated using eggs from three sturgeon and sperm from four paddlefish individuals. Survival in all hybrid family groups ranged from 62% to 74% 30 days after hatching. This was the first successful hybridization between these two species and between members of the family Acipenseridae and Polyodontidae. Flow cytometry and chromosome analysis revealed two ploidy levels in hybrids. The chromosome numbers of the hybrids ranged between 156–184 and 300–310, in “functional” triploids and “functional” pentaploids, respectively. The hybrid origin and the ploidy levels were also confirmed by microsatellite analyses. In hybrids, the size and the number of dorsal and ventral scutes correlated with the ploidy levels as well as with the calculated ratio of the maternal and paternal chromosome sets. An extra haploid cell lineage was found in three hybrid individuals irrespective of the ploidy level, suggesting polyspermy. Although the growth performance showed high variance in hybrids (mean: 1.2 kg, SD: 0.55), many individuals reached a size of approximately 1 kg by the age of one year under intensive rearing conditions.
Estimating the Magnitude of Illicit Cigarette Trade in Bangladesh: Protocol for a Mixed-Methods Study
Authors: Abdullah S. M. , Huque Rumana , Bauld Linda , Ross Hana , Gilmore Anna , John Rijo M. , Dobbie Fiona , Siddiqi Kamran
Published: July 2020

The illicit tobacco trade undermines the effectiveness of tobacco tax policies; increases the availability of cheap cigarettes, which, in turn, increases tobacco use and tobacco related deaths; and causes huge revenue losses to governments. There is limited evidence on the extent of illicit tobacco trade particularly cigarettes in Bangladesh. The paper presents the protocol for a mixed-methods study to estimate the extent of illicit cigarette trade in Bangladesh. The study will address three research questions: (a) What proportion of cigarettes sold as retail are illicit? (b) What are the common types of tax avoidance and tax evasion? (c) Can pack examination from the trash recycle market be considered as a new method to assess illicit trade in comparison to that from retailers and streets? Following an observational research method, data will be collected utilizing empty cigarette packs from three sources: (a) retailers; (b) streets; and (c) trash recycle market. In addition, a structured questionnaire will be used to collect information from retailers selling cigarettes. We will select post codes as Primary Sampling Unit (PSU) using a multi-stage random sampling technique. We will randomly select eight districts from eight divisions stratified by those with land border and non-land border; and within each district, we will randomly select ten postcodes, stratified by rural (five) and urban (five) PSU to ensure maximum geographical variation, leading to a total of eighty post codes from eight districts. The analysis will report the proportions of packs that do not comply with the study definition of illicit. Independent estimates of illicit tobacco are rare in low- and middle-income countries such as Bangladesh. Findings will inform efforts by revenue authorities and others to address the effects of illicit trade and counter tobacco industry claims.
Climate Change Impacts on Agricultural Production and Crop Disaster Area in China
Authors: Shi Zhen , Huang Huinan , Wu Yingju , Chiu Yung-Ho , Qin Shijiong
Published: July 2020

As one of the largest agricultural countries in the world, China has always paid close attention to the sustainable development of agricultural production efficiency. However, with global climate change, extreme weather has become an exogenous factor that cannot be ignored, as it affects agricultural production. Most of the existing studies only consider the domestic natural resources and economic factors, without fully considering the external climate factors. This paper uses the super undesirable dynamic Slacks-Based Measures (SBM) under an exogenous variable model to simulate the external environmental factors by adding extreme weather days. The Dagum Gini coefficient and kernel density estimation are used to explore the regional differences in agricultural production in China. The results show that the agricultural production efficiency is higher in the eastern region, and the difference in agricultural production efficiency among the provinces in the middle and western regions is large, showing a trend of polarization. The difference in the Gini coefficient between the middle and western regions is more significant. The main contribution factor of the Dagum Gini coefficient is the inter-regional difference. The regional concentration degree of agriculture in China is decreasing, the regional distribution of agricultural water resources is more balanced, and the national regional difference gradually decreases. Finally, some suggestions are put forward, such as extreme weather control, agricultural water supply, and water-saving measures.
Exposure to New Emerging Bisphenols Among Young Children in Switzerland
Authors: Lucarini Fiorella , Krasniqi Tropoja , Bailat Rosset Gaëlle , Roth Nicolas , Hopf Nancy B , Broillet Marie-Christine , Staedler Davide
Published: July 2020

Restrictions on the use of bisphenol A (BPA) in consumer products led to its replacement by various bisphenol (BP) analogues, yet young children’s exposure to these analogues has been poorly characterized so far. This study aimed to characterize infants’ and toddlers’ exposure to BPA and 14 emerging BP analogues (i.e., bisphenol AF, bisphenol AP, bisphenol B, bisphenol BP, bisphenol C (BPC), bisphenol E, bisphenol F (BPF), bisphenol G, bisphenol M (BPM), bisphenol P, bisphenol PH, bisphenol S (BPS), bisphenol TMC, and bisphenol Z). We extracted infants’ and toddlers’ urine from diapers (n = 109) collected in Swiss daycare centers as a practical and noninvasive alternative approach to urinary biomonitoring. Bisphenols were present in 47% of the samples, with BPC and BPM being the most frequently detected (23% and 25% of all samples, respectively). The mean concentrations of urinary BPS and BPF were greater than that of BPA. This contrasts with data reported previously. Furthermore, statistical analysis revealed a significant and negative correlation between urinary BPM concentration and the population’s age. Our results provide a first characterization of infants’ and toddlers’ exposure to bisphenols in Switzerland. This knowledge can be used to support ongoing biomonitoring studies and to prioritize exposure reduction and prevention strategies.
Interaction of Socioeconomic Status with Risky Internet Use, Gambling and Substance Use in Adolescents from a Structurally Disadvantaged Region in Central Europe
Authors: Petruzelka Benjamin , Vacek Jaroslav , Gavurova Beata , Kubak Matus , Gabrhelik Roman , Rogalewicz Vladimir , Bartak Miroslav
Published: July 2020

Background and aims: The current level of knowledge concerning the effect of socioeconomic status (SES) on internet use, gambling, and substance use in structurally disadvantaged regions is scarce. The objective of this study was an investigation of the relationship between SES and risky internet use, gambling and substance use in a structurally disadvantaged region in Central Europe. Methods: A cross-sectional survey was conducted among high school students (n = 1063) in a Czech structurally disadvantaged region in autumn 2017. Binary Logistic Regression models were applied to data from the modified Excessive Internet Use scale (mEIUS), a standard tool for measuring the risk of addictive behavior on the internet and the risk of excessive gaming. Other data were collected using the Lie/Bet (problematic gambling), CAGE (acronym of the key words: cut, angry, guilty and eye-opener), and the Cannabis Abuse Screening Test (CAST) (problematic alcohol/cannabis use) tools. Results: There were statistically significant differences between at-risk and not-at-risk groups in addictive behavior on the internet and gaming, while none were found in problematic gambling. Individual dimensions of SES showed significant effects on substance use. Regarding parenting styles, significant differences were found only in the risk of addictive behavior on the internet or gaming between the authoritarian and authoritative styles. Being engaged in behavioral addictions with one´s parents increased the odds of the behavioral addiction risk and decreased the odds of the substance addiction risk. Engagement with one´s parents in substance addictions decreased the odds of the behavioral addiction risk and increased the odds of the substance addiction risk. Discussion and Conclusions: The results point at specific relations between SES and the risk of addictive behaviors on the internet and gaming within structurally disadvantaged regions. The results of SES and/or structurally disadvantaged region measures obtained in research, policy-making, and care-provision may improve the focus of actions taken.
Process Evaluation of a School-Based Program Aimed at Preventing Obesity in Adolescents from Lima and Callao, Peru
Authors: Cosme Chavez Rosemary , Nam Eun Woo
Published: July 2020

The study aims to describe process evaluation measures of the three-year Health Promoting Schools’ obesity prevention program in Lima and Callao, Peru, and to assess factors that influenced the implementation of the intervention leading to the mentioned process outcomes results. The program was implemented in four public high schools located in low-income areas of Lima and Callao. Embedded in a Health Promoting School Intervention, the program consisted of two main components—an education program and several environmental activities. Quantitative data were collected and analyzed based on dose delivered and reach for each specific activity. Dose received was analyzed by satisfaction scores related to six specific activities. Furthermore, qualitative data including documentation of activities and transcriptions from individual in-depth interviews were qualitatively analyzed to identify factors influencing the implementation. The education component of the Health Promoting Schools’ program achieved a 78.4% average nutrition sessions delivery in 2015 and 88.0% in 2017; while for PA sessions, the average delivery in 2015 was of 79.7% and 93.8% in 2017. In the case of reach, at least 75% of total students participated in all sessions per year. Nevertheless, there were differences in terms of delivery and participation in a number of environmental activities within and between schools during the program period. Differences in delivery included education sessions for parents, teachers, Junior Health Promoters, and school food kiosk staff, besides execution of physical activity events every year. Impeding factors included the complexity of the overall intervention, limited strategies to facilitate program implementation and those to maintain the participation of subjects, and related contextual factors.
A Review on the Prevalence of Toxoplasma gondii in Humans and Animals Reported in Malaysia from 2008–2018
Authors: Nasiru Wana Mohammed , Mohd Moklas Mohamad Aris , Watanabe Malaika , Nordin Norshariza , Zasmy Unyah Ngah , Alhassan Abdullahi Sharif , Ahmad Issa Alapid Ashraf , Mustapha Tijjani , Basir Rusliza , Abd. Majid Roslaini
Published: July 2020

Toxoplasmosis is a disease caused by the protozoan parasite Toxoplasma gondii (T. gondii). Human toxoplasmosis seroprevalence in Malaysia has increased since it was first reported in 1973 as shown in previous reviews of 1991 and 2007. However, over a decade since the last review, comprehensive data on toxoplasmosis in Malaysia is lacking. This work aimed at reviewing articles on toxoplasmosis research in Malaysia in order to identify the research gaps, create public awareness, and efforts made so far and proffer management options on the disease. The present review examines the available published research articles from 2008 to 2018 related to toxoplasmosis research conducted in Malaysia. The articles reviewed were retrieved from nine credible databases such as Web of Science, Google Scholar, ScienceDirect, PubMed, Scopus, Springer, Wiley online library, Ovid, and Cochrane using the keywords; Malaysia, toxoplasmosis, Toxoplasma gondii, toxoplasma encephalitis, seroprevalence, human immunodeficiency virus (HIV) patients, pregnant women, genotype strain, anti-toxoplasma antibodies, felines, and vaccine. The data highlighted seropositive cases from healthy community members in Pangkor Island (59.7%) and among migrant workers (57.4%) at alarming rates, as well as 42.5% in pregnant women. Data on animal seroprevalence were limited and there was no information on cats as the definitive host. Genetic characterization of Toxoplasma gondii from HIV patients; pregnant women, and domestic cats is lacking. This present review on toxoplasmosis is beneficial to researchers, health workers, animal health professionals, and policymakers. Therefore, attention is required to educate and enlighten health workers and the general public about the risk factors associated with T. gondii infection in Malaysia.
Managing a Tertiary Orthopedic Hospital during the COVID-19 Epidemic, Main Challenges and Solutions Adopted
Authors: Magro Francesco , Perazzo Paolo , Bottinelli Elena , Possenti Francesco , Banfi Giuseppe
Published: July 2020

The present paper is a review of the main challenges faced by the management of a tertiary specialty hospital during the COVID-19 pandemic in the northern Italian region of Lombardy, an area of extremely high epidemic impact. The article focuses on the management of patient flows, access to the hospital, maintaining and reallocating staffing levels, and managing urgent referrals, information, and communications from the point of view of the hospital managers over a seven-week period. The objective of the article is to provide beneficial insights and solutions to other hospital managers and medical directors who should find themselves in the same or a similar situation. In such an epidemic emergency, in the authors’ opinion, the most important factors influencing the capability of the hospital to maintain operations are (1) sustaining the strict triage of patients, (2) the differentiation of flows and pathways to create what could be regarded as “a hospital inside a hospital”, (3) tracing and sharing all available information to face the rapidly changing environment, (4) being able to maintain staffing levels in critical areas by flexibly allocating the workforce, and (5) from a regional perspective, being organized along a hub-and-spoke system for critical and time-sensitive networks was key for focusing the hospital’s resources on the most needed services.