bluuebunny/crossref_metadata_2025 huggingface dataset:
Significant Impacts of Work-Related Cerebrovascular and Cardiovascular Diseases among Young Workers: A Nationwide Analysis
Authors: Hsu Ya-Yuan , Wang Ray , Bai Chyi-Huey
Published: March 2019

Background: While occupational factors linked to the onset of cerebrovascular and cardiovascular diseases (CVDs) have been reported among workers, much remains unknown about the impacts that occupation has on the onset of CVDs in various age groups. We attempted to describe temporal trends in total and work-related CVDs (WRCVDs) rates stratified by age and year and explore the relative contributions of work to the CVD risk. Methods: This study was conducted using two populations from the Labor Insurance Database as the working population and the National Health Insurance Research Database as the general population. We included all people aged 15–75 years from 2006 to 2013. All CVD events and WRCVD events were identified. A Poisson regression was used to estimate the morbidity rate ratio (RR) stratified by age and period, and an RR adjusted for residual confounding was also used. Results: Incident CVD rates increased with aging in the general population (from 1113.55 to 1853.32 per 100,000 persons), and WRCVD rates increased in the working population over time (from 2.10 in 2006 to 8.60 in 2013 per 100,000 persons). In the age and period analysis, CVD attacks showed disparities in different populations. The RR of the WRCVD risk was mainly in the working population aged >45 years, and the RR of the CVD risk occurred in the oldest group (aged 55–64 years) of the general population. The population-attributable risk of working exposure was 13.5%. After eliminating residual confounding factors, higher population attributed risk (PAR) work-related excessive CVD risk mainly occurred in workers aged 25–34 and 35–44 years. A decreasing PAR trend was found in the age groups as follows: 15–24, 25–34, 35–44, 45–54, and 55–64 years, with percentages of 17.64%, 16.89%, 16.46%, 10.6%, and 0.65%, respectively. Conclusions: There is evidence that period and age trends of CVD rates differed between the working population and general population. Relative effects attributed to work were more severe in younger workers, particularly in workers aged <55 years.
Asking Sensitive Questions Using the Randomized Response Approach in Public Health Research: An Empirical Study on the Factors of Illegal Waste Disposal
Authors: Chong Andy C. Y. , Chu Amanda M. Y. , So Mike K. P. , Chung Ray S. W.
Published: March 2019

A survey study is a research method commonly used to quantify population characteristics in biostatistics and public health research, two fields that often involve sensitive questions. However, if answering sensitive questions could cause social undesirability, respondents may not provide honest responses to questions that are asked directly. To mitigate the response distortion arising from dishonest answers to sensitive questions, the randomized response technique (RRT) is a useful and effective statistical method. However, research has seldom addressed how to apply the RRT in public health research using an online survey with multiple sensitive questions. Thus, we help fill this research gap by employing an innovative unrelated question design method. To illustrate how the RRT can be implemented in a multivariate analysis setting, we conducted a survey study to examine the factors affecting the intention of illegal waste disposal. This study demonstrates an application of the RRT to investigate the factors affecting people’s intention of illegal waste disposal. The potential factors of the intention were adopted from the theory of planned behavior and the general deterrence theory, and a self-administered online questionnaire was employed to collect data. Using the RRT, a covariance matrix was extracted for examining the hypothesized model via structural equation modeling. The survey results show that people’s attitude toward the behavior and their perceived behavioral control significantly positively affect their intention. This paper is useful for showing researchers and policymakers how to conduct surveys in environmental or public health related research that involves multiple sensitive questions.
Applicability of Remote Sensing-Based Vegetation Water Content in Modeling Lightning-Caused Forest Fire Occurrences
Authors: Abdollahi Masoud , Dewan Ashraf , Hassan Quazi K.
Published: March 2019

In this study, our aim was to model forest fire occurrences caused by lightning using the variable of vegetation water content over six fire-dominant forested natural subregions in Northern Alberta, Canada. We used eight-day composites of surface reflectance data at 500-m spatial resolution, along with historical lightning-caused fire occurrences during the 2005–2016 period, derived from a Moderate Resolution Imaging Spectroradiometer. First, we calculated the normalized difference water index (NDWI) as an indicator of vegetation/fuel water content over the six natural subregions of interest. Then, we generated the subregion-specific annual dynamic median NDWI during the 2005–2012 period, which was assembled into a distinct pattern every year. We plotted the historical lightning-caused fires onto the generated patterns, and used the concept of cumulative frequency to model lightning-caused fire occurrences. Then, we applied this concept to model the cumulative frequencies of lightning-caused fires using the median NDWI values in each natural subregion. By finding the best subregion-specific function (i.e., R2 values over 0.98 for each subregion), we evaluated their performance using an independent subregion-specific lightning-caused fire dataset acquired during the 2013–2016 period. Our analyses revealed strong relationships (i.e., R2 values in the range of 0.92 to 0.98) between the observed and modeled cumulative frequencies of lightning-caused fires at the natural subregion level throughout the validation years. Finally, our results demonstrate the applicability of the proposed method in modeling lightning-caused fire occurrences over forested regions.
Use of Materials Based on Polymeric Silica as Bone-Targeted Drug Delivery Systems for Metronidazole
Authors: Czarnobaj Katarzyna , Prokopowicz Magdalena , Greber Katarzyna
Published: March 2019

Mesostructured ordered silica-based materials are the promising candidates for local drug delivery systems in bone disease due to their uniform pore size and distribution, and high surface area which affect their excellent adsorption properties, good biocompatibility and bioactivity, and versatile functionalization so that their properties can be controlled. Ordered mesoporous silica (MCM-41 type) was synthesized by a surfactant-assisted sol-gel process using tetraethoxysilane as a silica precursor and hexadecyltrimethylammonium bromide as the structure-directing agent. Functionalized silica materials containing various types of organic groups (3-aminopropyl, 3-mercaptopropyl, or 3-glycidyloxypropyl groups) were synthesized by the post-grafting method onto pre-made mesoporous silica. Comparative studies of their structural characteristics, the surface mineralization activity and release properties for the model drug Metronidazole (MT) were then conducted. It has been found that porosity parameters, mineralization activity and adsorption/release of metronidazole from mesoporous channels of silica can be regulated using functional groups which are chemically bounded with an outer silica surface. The preferential mineral nucleation was found on negatively charged surfaces—MCM-41, and mercaptopropyl and glycidyloxypropyl functionalized silica (MCM-SH and MCM-epoxy, respectively) in simulated body fluid (SBF solution), as well as a sustained release of MT. In contrast to them, aminopropyl-functionalized samples (MCM-NH2) achieved a high MT release rate. These results confirm the potential of silica-based materials for local therapeutic applications (as drug carriers and bone substitutes) in bone disease.
Understanding Immune Evasion and Therapeutic Targeting Associated with PD-1/PD-L1 Pathway in Diffuse Large B-cell Lymphoma
Authors: Song Moo-Kon , Park Byeong-Bae , Uhm Jieun
Published: March 2019

In tumor microenvironment, the programmed death 1 (PD-1) immune checkpoint has a crucial role of mechanism of T cell exhaustion leading to tumor evasion. Ligands of PD-1, programmed death ligand 1/2 (PD-L1/L2) are over-expressed in tumor cells and participate in prolonged tumor progression and survivals. Recently, clinical trials for patients who failed to obtain an optimal response prior to standardized chemotherapy in several solid cancers have been focused on targeting therapy against PD-1 to reduce disease progression rates and prolonged survivals. Since various inhibitors targeting the immune checkpoint in PD-1/PD-L1 pathway in solid cancers have been introduced, promising approach using anti-PD-1 antibodies were attempted in several types of hematologic malignances. In diffuse large B cell lymphoma (DLBCL) as the most common and aggressive B cell type of non-Hodgkin’s lymphoma, anti-PD-1 and anti-PD-L1 antibodies were studies in various clinical trials. In this review, we summarized the results of several studies associated with PD-1/PD-L1 pathway as an immune evasion mechanism and described clinical trials about targeting therapy against PD-1/PD-L1 pathway in DLBCL.
Single Injection of High Volume of Autologous Pure PRP Provides a Significant Improvement in Knee Osteoarthritis: A Prospective Routine Care Study
Authors: Guillibert Caroline , Charpin Caroline , Raffray Marie , Benmenni Annie , Dehaut Francois-Xavier , El Ghobeira Georges , Giorgi Roch , Magalon Jeremy , Arniaud Denis
Published: March 2019

Background: Evidence is growing regarding the ability of platelet-rich plasma (PRP) injections to enhance functional capacity and alleviate pain in knee osteoarthritis (OA). However, heterogeneity in common practice regarding PRP preparation and biological content makes the initiation of this activity in a hospital complex. The aim of this study was to document the efficacy of a single PRP injection to treat knee OA and validate a routine care procedure. Methods: Fifty-seven patients with symptomatic knee OA received a single injection of large volume of very pure PRP. They were assessed at baseline and after one, three and six months, by measuring Knee Injury and Osteoarthritis Score (KOOS), Observed Pain after a 50-foot walk test and Visual Analog Scale (VAS) assessments. Magnetic Resonance Imaging (MRI) analysis was performed at baseline and six months after the procedure. The objective was to recover 50% of responders three months after the procedure using OMERACT-OARSI criteria. Results: A single administration of high volume pure PRP provided significant clinical benefit for 84.2% of the responders, three months after the procedure. The KOOS total score significantly increased from 43.5 ± 14.3 to 66.4 ± 21.7 six months after the procedure (p < 0.001). Pain also significantly decreased from 37.5 ± 25.1 to 12.9 ± 20.9 (p < 0.001). No difference was observed on MRI parameters. Conclusion: A single injection of large volume of very pure PRP is associated with significant functional improvement and pain relief, allowing initiation of daily PRP injection within our hospital.
PFKFB2 Promoter Hypomethylation as Recurrence Predictive Marker in Well-Differentiated Thyroid Carcinomas
Authors: Camargo Barros-Filho Mateus , Barreto Menezes de Lima Larissa , Bisarro dos Reis Mariana , Bette Homem de Mello Julia , Moraes Beltrami Caroline , Lopes Pinto Clóvis Antonio , Kowalski Luiz Paulo , Rogatto Silvia Regina
Published: March 2019

Despite the low mortality rates, well-differentiated thyroid carcinomas (WDTC) frequently relapse. BRAF and TERT mutations have been extensively related to prognosis in thyroid cancer. In this study, the methylation levels of selected CpGs (5-cytosine-phosphate-guanine-3) comprising a classifier, previously reported by our group, were assessed in combination with BRAF and TERT mutations. We evaluated 121 WDTC, three poorly-differentiated/anaplastic thyroid carcinomas (PDTC/ATC), 22 benign thyroid lesions (BTL), and 13 non-neoplastic thyroid (NT) tissues. BRAF (V600E) and TERT promoter (C228T and C250T) mutations were tested by pyrosequencing and Sanger sequencing, respectively. Three CpGs mapped in PFKFB2, ATP6V0C, and CXXC5 were evaluated by bisulfite pyrosequencing. ATP6V0C hypermethylation and PFKFB2 hypomethylation were detected in poor-prognosis (PDTC/ATC and relapsed WDTC) compared with good-prognosis (no relapsed WDTC) and non-malignant cases (NT/BTL). CXXC5 was hypomethylated in both poor and good-prognosis cases. Shorter disease-free survival was observed in WDTC patients presenting lower PFKFB2 methylation levels (p = 0.004). No association was observed on comparing BRAF (60.7%) and TERT (3.4%) mutations and prognosis. Lower PFKFB2 methylation levels was an independent factor of high relapse risk (Hazard Ratio = 3.2; CI95% = 1.1–9.5). PFKFB2 promoter methylation analysis has potential applicability to better stratify WDTC patients according to the recurrence risk, independently of BRAF and TERT mutations.
Artificial Light at Night Alleviates the Negative Effect of Pb on Freshwater Ecosystems
Authors: Pu Gaozhong , Zeng Danjuan , Mo Ling , Liao Jianxiong , Chen Xiaxia
Published: March 2019

Artificial light at night (ALAN) is an increasing phenomenon worldwide that can cause a series of biological and ecological effects, yet little is known about its potential interaction with other stressors in aquatic ecosystems. Here, we tested whether the impact of lead (Pb) on litter decomposition was altered by ALAN exposure using an indoor microcosm experiment. The results showed that ALAN exposure alone significantly increased leaf litter decomposition, decreased the lignin content of leaf litter, and altered fungal community composition and structure. The decomposition rate was 51% higher in Pb with ALAN exposure treatments than in Pb without ALAN treatments, resulting in increased microbial biomass, β-glucosidase (β-G) activity, and the enhanced correlation between β-G and litter decomposition rate. These results indicate that the negative effect of Pb on leaf litter decomposition in aquatic ecosystems may be alleviated by ALAN. In addition, ALAN exposure also alters the correlation among fungi associated with leaf litter decomposition. In summary, this study expands our understanding of Pb toxicity on litter decomposition in freshwater ecosystems and highlights the importance of considering ALAN when assessing environmental metal pollutions.
Fatty Acid Synthesis and Degradation Interplay to Regulate the Oxidative Stress in Cancer Cells
Authors: Mikalayeva Valeryia , Ceslevičienė Ieva , Sarapinienė Ieva , Žvikas Vaidotas , Skeberdis Vytenis Arvydas , Jakštas Valdas , Bordel Sergio
Published: March 2019

Both cytosolic fatty acid synthesis (FAS) and mitochondrial fatty acid oxidation (FAO) have been shown to play a role in the survival and proliferation of cancer cells. This study aimed to confirm experimentally whether FAS and FAO coexist in breast cancer cells (BCC). By feeding cells with 13C-labeled glutamine and measuring labeling patterns of TCA intermediates, it was possible to show that part of the cytosolic acetyl-CoA used in lipid synthesis is also fed back into the mitochondrion via fatty acid degradation. This results in the transfer of reductive potential from the cytosol (in the form of NADPH) to the mitochondrion (in the form of NADH and FADH2). The hypothesized mechanism was further confirmed by blocking FAS and FAO with siRNAs. Exposure to staurosporine (which induces ROS production) resulted in the disruption of simultaneous FAS and FAO, which could be explained by NADPH depletion.
Comparative Transcriptome Combined with Proteome Analyses Revealed Key Factors Involved in Alfalfa (Medicago sativa) Response to Waterlogging Stress
Authors: Zeng Ningbo , Yang Zhijian , Zhang Zhifei , Hu Longxing , Chen Liang
Published: March 2019

Alfalfa (Medicago sativa) is the most widely grown and most important forage crop in the world. However, alfalfa is susceptible to waterlogging stress, which is the major constraint for its cultivation area and crop production. So far, the molecular mechanism of alfalfa response to the waterlogging is largely unknown. Here, comparative transcriptome combined with proteomic analyses of two cultivars (M12, tolerant; M25, sensitive) of alfalfa showing contrasting tolerance to waterlogging were performed to understand the mechanism of alfalfa in response to waterlogging stress. Totally, 748 (581 up- and 167 down-regulated) genes were differentially expressed in leaves of waterlogging-stressed alfalfa compared with the control (M12_W vs. M12_CK), whereas 1193 (740 up- and 453 down-regulated) differentially abundant transcripts (DATs) were detected in the leaves of waterlogging-stressed plants in comparison with the control plants (M25_W vs. M25_CK). Furthermore, a total of 187 (122 up- and 65 down-regulated) and 190 (105 up- and 85 down-regulated) differentially abundant proteins (DAPs) were identified via isobaric tags for relative and absolute quantification (iTRAQ) method in M12_W vs. M12_CK and M25_W vs. M25_CK comparison, respectively. Compared dataset analysis of proteomics and transcriptomics revealed that 27 and eight genes displayed jointly up-regulated or down-regulated expression profiles at both mRNA and protein levels in M12_W vs. M12_CK comparison, whereas 30 and 27 genes were found to be co-up-regulated or co-down-regulated in M25_W vs. M25_CK comparison, respectively. The strongly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for co-up-regulated genes at mRNA and protein levels in M12_W vs. M12_CK comparison were ‘Amino sugar and nucleotide sugar metabolism’, ‘Arginine and proline metabolism’ and ‘Starch and sucrose metabolism’, whereas co-up-regulated protein-related pathways including ‘Arginine and proline metabolism’ and ‘Valine, leucine and isoleucine degradation’ were largely enriched in M25_W vs. M25_CK comparison. Importantly, the identified genes related to beta-amylase, Ethylene response Factor (ERF), Calcineurin B-like (CBL) interacting protein kinases (CIPKs), Glutathione peroxidase (GPX), and Glutathione-S-transferase (GST) may play key roles in conferring alfalfa tolerance to waterlogging stress. The present study may contribute to our understanding the molecular mechanism underlying the responses of alfalfa to waterlogging stress, and also provide important clues for further study and in-depth characterization of waterlogging-resistance breeding candidate genes in alfalfa.
An Efficient Image Reconstruction Framework Using Total Variation Regularization with Lp-Quasinorm and Group Gradient Sparsity
Authors: Lin Fan , Chen Yingpin , Wang Lingzhi , Chen Yuqun , Zhu Wei , Yu Fei
Published: March 2019

The total variation (TV) regularization-based methods are proven to be effective in removing random noise. However, these solutions usually have staircase effects. This paper proposes a new image reconstruction method based on TV regularization with Lp-quasinorm and group gradient sparsity. In this method, the regularization term of the group gradient sparsity can retrieve the neighborhood information of an image gradient, and the Lp-quasinorm constraint can characterize the sparsity of the image gradient. The method can effectively deblur images and remove impulse noise to well preserve image edge information and reduce the staircase effect. To improve the image recovery efficiency, a Fast Fourier Transform (FFT) is introduced to effectively avoid large matrix multiplication operations. Moreover, by introducing accelerated alternating direction method of multipliers (ADMM) in the method to allow for a fast restart of the optimization process, this method can run faster. In numerical experiments on standard test images sourced form Emory University and CVG-UGR (Computer Vision Group, University of Granada) image database, the advantage of the new method is verified by comparing it with existing advanced TV-based methods in terms of peak signal-to-noise ratio (PSNR), structural similarity (SSIM), and operational time.
Improvement in the Efficiency of a Distributed Multi-Label Text Classification Algorithm Using Infrastructure and Task-Related Data
Authors: Sarnovsky Martin , Olejnik Marek
Published: March 2019

Distributed computing technologies allow a wide variety of tasks that use large amounts of data to be solved. Various paradigms and technologies are already widely used, but many of them are lacking when it comes to the optimization of resource usage. The aim of this paper is to present the optimization methods used to increase the efficiency of distributed implementations of a text-mining model utilizing information about the text-mining task extracted from the data and information about the current state of the distributed environment obtained from a computational node, and to improve the distribution of the task on the distributed infrastructure. Two optimization solutions are developed and implemented, both based on the prediction of the expected task duration on the existing infrastructure. The solutions are experimentally evaluated in a scenario where a distributed tree-based multi-label classifier is built based on two standard text data collections.
On the Theoretical CO2 Sequestration Potential of Pervious Concrete
Authors: Ellingboe Ethan , Arehart Jay H. , Srubar Wil V.
Published: March 2019

Pervious concrete, which has recently found new applications in buildings, is both energy- and carbon-intensive to manufacture. However, similar to normal concrete, some of the initial CO2 emissions associated with pervious concrete can be sequestered through a process known as carbonation. In this work, the theoretical formulation and application of a mathematical model for estimating the carbon dioxide (CO2) sequestration potential of pervious concrete is presented. Using principles of cement and carbonation chemistry, the model related mixture proportions of pervious concretes to their theoretical in situ CO2 sequestration potential. The model was subsequently employed in a screening life cycle assessment (LCA) to quantify the percentage of recoverable CO2 emissions—namely, the ratio of in situ sequesterable CO2 to initial cradle-to-gate CO2 emissions—for common pervious concrete mixtures. Results suggest that natural carbonation can recover up to 12% of initial CO2 emissions and that CO2 sequestration potential is maximized for pervious concrete mixtures with (i) lower water-to-cement ratios, (ii) higher compressive strengths, (iii) lower porosities, and (iv) lower hydraulic conductivities. However, LCA results elucidate that mixtures with maximum CO2 sequestration potential (i.e., mixtures with high cement contents and CO2 recoverability) emit more CO2 from a net-emissions perspective, despite their enhanced in situ CO2 sequestration potential.
How Cabbage Aphids Brevicoryne brassicae (L.) Make a Choice to Feed on Brassica napus Cultivars
Authors: Hao Zhong-Ping , Zhan Hai-Xia , Wang Yu-Long , Hou Shu-Min
Published: March 2019

Plant resistance to aphids might be present in different plant tissues, such as the epidermis, mesophyll and phloem, but not all of them play a key role in determining the feeding preference of aphids. In this study, electrically recorded feeding behaviors of cabbage aphids were combined with choice tests and microscopic observations to understand the feeding preference of cabbage aphids on oilseed rape cultivars. The choice tests showed that more cabbage aphids survived on ‘Qianyou18’, and less on ‘Zhongshuang11’, compared with the other cultivars. The results of the choice tests were paradoxical with the results analyzed from the general and mesophyll-associated variables. The thick upper epidermis with bushy long trichomes on the leaves of ‘Zhongshuang11’ delayed the first probe of the cabbage aphids. The duration of phloem-feeding was similar among the four cultivars although there were differences in the hindrance of the mesophyll. However, salivation was increased when the aphids fed on ‘Zhongshuang11’, further indicating that the leaf’s physical properties could be important for aphid feeding preference on the four cultivars.
High-Beta Optics and Running Prospects
Authors: Burkhardt Helmut
Published: March 2019

Dedicated high-beta optics are used to make forward proton scattering measurements possible at the LHC. Following a short general introduction and history of special high-beta optics and running conditions, we describe the two types of special high-beta runs planned for 2018. A run at top energy at β y * = 90 m for elastic and diffractive scattering, and a low energy run to measure the rho-parameter in the Coulomb interference region.
Gender Dictates the Relationship between Serum Lipids and Leukocyte Counts in the National Health and Nutrition Examination Survey 1999–2004
Authors: Andersen Catherine J. , Vance Terrence M.
Published: March 2019

Dyslipidemias and leukocytosis are associated with cardiovascular disease and immune disorders. Mechanistic studies have shown lipoprotein metabolism to play a significant role in the regulation of atherosclerosis development and leukocyte activation, whereas lipid-lowering treatments have been shown to exert beneficial anti-inflammatory and immunomodulatory effects in clinical trials. However, the relationship between clinical markers of lipid metabolism and leukocyte counts has not been extensively evaluated at the population level. We aimed to determine whether clinical blood lipid measures are associated with leukocyte counts in the general U.S. population represented in the National Health and Nutrition Examination Survey (NHANES) 1999–2004, and whether differences exist between men and women (n = 5647). We observed a strong positive linear trend between serum triglycerides vs. blood lymphocyte and basophil counts in both men and women, whereas a positive trend between monocytes vs. triglycerides and lymphocytes vs. total cholesterol and LDL-cholesterol (LDL-C) was only detected in women. Conversely, HDL-C was inversely associated with a greater number of leukocyte subsets in men, whereas inverse trends between HDL-C vs. lymphocytes were observed in both men and women. In multiple regression models, a 10% increase in total cholesterol, LDL-C, and triglycerides was associated with a predicted 1.6%, 0.6%, and 1.4% increase in blood lymphocyte counts in women, respectively, whereas no relationship was observed in men. In both men and women, a 10% increase in triglycerides was additionally associated with higher lymphocyte, neutrophil, and basophil counts, whereas 10% increases in HDL-cholesterol were associated with significantly lower lymphocyte, neutrophil, eosinophil, and basophil counts in men, in addition to lower lymphocyte and monocyte counts in women. These findings suggest that clinical lipid markers may be used to predict blood leukocyte distributions, and that a gender-specific relationship exists between distinct classes of serum lipids and immune cell subsets.
Fimasartan for Remodeling after Myocardial Infarction
Authors: Lim Byung-Kwan , Park Jin Joo , Park Sung-Ji , Lee You-Jung , Kwon Jin-Sook , Kim Eun-Ji , Choi Dong-Ju
Published: March 2019

An angiotensin receptor blocker (ARB) mitigates cardiac remodeling after myocardial infarction (MI). Here, we investigated the effect of fimasartan, a new ARB, on cardiac remodeling after MI. Sprague–Dawley rats were assigned into 3 groups: surgery only (sham group, n = 7), MI without (MI-only group, n = 13), and MI with fimasartan treatment (MI + Fima group, n = 16). MI was induced by the permanent ligation of the left anterior descending artery. Treatment with fimasartan (10 mg/kg) was initiated 24 h after MI and continued for 7 weeks. Rats in the MI + Fima group had a higher mean ejection fraction (66.3 ± 12.5% vs. 51.3 ± 14.8%, P = 0.002) and lower left ventricular end-diastolic diameter (9.14 ± 1.11 mm vs. 9.91 ± 1.43 mm, P = 0.045) than those in the MI-only group at 7 weeks after MI. The infarct size was lower in the MI + Fima than in the MI group (P < 0.05). A microarray analysis revealed that the expression of genes related to the lipid metabolism and mitochondrial membrane ion transporters were upregulated, and those involved in fibrosis and inflammation were downregulated by fimasartan. Fimasartan attenuates cardiac remodeling and dysfunction in rats after MI and may prevent the progression to heart failure after MI.
The Clinical Trial Landscape for Melanoma Therapies
Authors: Wróbel Sonia , Przybyło Małgorzata , Stępień Ewa
Published: March 2019

(1) Despite many years of research, melanoma still remains a big challenge for modern medicine. The purpose of this article is to review publicly available clinical trials to find trends regarding the number of trials, their location, and interventions including the most frequently studied drugs and their combinations. (2) We surveyed clinical trials registered in the International Clinical Trials Registry Platform (ICTRP), one of the largest databases on clinical trials. The search was performed on 30 November 2018 using the term “melanoma”. Data have been supplemented with the information obtained from publicly available data repositories including PubMed, World Health Organization, National Cancer Institute, Centers for Disease Control and Prevention, European Cancer Information System, and many others to bring the historical context of this study. (3) Among the total of 2563 clinical trials included in the analysis, most have been registered in the USA (1487), which is 58% of the total. The most commonly studied drug in clinical trials was ipilimumab, described as applied intervention in 251 trials. (4) An increase in the number of melanoma clinical trials using immunomodulating monoclonal antibody therapies, small molecule-targeted therapies (inhibitors of BRAF, MEK, CDK4/6), and combination therapies is recognized. This illustrates the tendency towards precision medicine.
The Scientific Response to Zika Virus
Authors: Martín-Acebes Miguel A. , Saiz Juan-Carlos
Published: March 2019

Zika virus (ZIKV) is a mosquito-borne pathogen that became renowned in 2015 in Brazil mainly due to its association with microcephaly in newborns. Although most infections in adults are asymptomatic or cause mild illnesses, in a reduced number of cases, ZIKV can also produce severe complications that include neurological disorders (Guillain–Barré syndrome), ocular lesions, or reproductive alterations. From 2015 the efforts of a significant part of the scientific community were placed on ZIKV research, which has resulted in an unpredicted escalation of the knowledge of the biology and pathology of this virus. The rapid response of the scientific community against ZIKV highlights its enormous potential to counter attack a viral threat within a short time period. It is expected that this huge collaborative effort will produce affordable and effective prophylactic and therapeutic tools against ZIKV. Nevertheless, there are still other arboviral threats different from ZIKV that should not be forgotten.
Potential Utility of Liquid Biopsy as a Diagnostic and Prognostic Tool for the Assessment of Solid Tumors: Implications in the Precision Oncology
Authors: Mathai Roshni Ann , Vidya Ryali Valli Sri , Reddy B. Shrikar , Thomas Levin , Udupa Karthik , Kolesar Jill , Rao Mahadev
Published: March 2019

Liquid biopsy is a technique that utilizes circulating biomarkers in the body fluids of cancer patients to provide information regarding the genetic landscape of the cancer. It is emerging as an alternative and complementary diagnostic and prognostic tool to surgical biopsy in oncology. Liquid biopsy focuses on the detection and isolation of circulating tumor cells, circulating tumor DNA and exosomes, as a source of genomic and proteomic information in cancer patients. Liquid biopsy is expected to provide the necessary acceleratory force for the implementation of precision oncology in clinical settings by contributing an enhanced understanding of tumor heterogeneity and permitting the dynamic monitoring of treatment responses and genomic variations. However, widespread implementation of liquid biopsy based biomarker-driven therapy in the clinical practice is still in its infancy. Technological advancements have resolved many of the hurdles faced in the liquid biopsy methodologies but sufficient clinical and technical validation for specificity and sensitivity has not yet been attained for routine clinical implementation. This article provides a comprehensive review of the clinical utility of liquid biopsy and its effectiveness as an important diagnostic and prognostic tool in colorectal, breast, hepatocellular, gastric and lung carcinomas which were the five leading cancer related mortalities in 2018.
Readiness for Firefighting: A Heart Transplant Patient’s Quest to Return to Work
Authors: Warburton Darren E. R. , Taylor Arlana , Jamnik Veronica K. , Gledhill Norman , Bredin Shannon S. D.
Published: March 2019

Heart transplantation patients generally demonstrate exercise capacities that are below the minimal standards for firefighting. Therefore, it is unlikely that heart transplantation patients will receive medical and/or employer clearance for active duty. We report a case of a firefighter who sought to return to full-time active duty following heart transplantation. We examined his physiological readiness to return to work during occupation-specific testing. Remarkably, the patient was able to meet the minimal requirements for full active firefighting. This finding provides direct evidence to support the potential of transplant patients returning to active duty in physiologically demanding occupations.
Electromagnetic Navigation Bronchoscopy Localization versus Percutaneous CT-Guided Localization for Lung Resection via Video-Assisted Thoracoscopic Surgery: A Propensity-Matched Study
Authors: Kuo Shuenn-Wen , Tseng Ying-Fan , Dai Kuan-Yu , Chang Yeun-Chung , Chen Ke-Cheng , Lee Jang-Ming
Published: March 2019

Background: An ideal preoperative localization method is essential for the resection of small and deep-seated pulmonary nodules by video-assisted thoracoscopic surgery (VATS) in the era of low-dose computed tomography (CT) screening. This study describes a new localization method using electromagnetic navigation bronchoscopy (ENB) and compares it against conventional percutaneous CT-guided methods. Methods: Between January 2016 and May 2018, 18 consecutive patients with a total of 27 pulmonary nodules underwent ENB localization using patent blue vital dye before thoracoscopy for lung resection at the National Taiwan University Hospital. Over the same period, 268 patients had a total of 325 pulmonary nodules localized by a CT-guided method. Propensity analysis was applied to minimize bias during comparison. Results: Patients were selected using a propensity-score based process, matched for potential risk factors for localization failure, to ensure equal potential prognostic factors in both groups. After matching, the ENB group had 15 patients with a total of 24 pulmonary nodules, and the CT group had 30 patients with 48 pulmonary nodules. No major procedure-related complications occurred in either group. The target pulmonary nodule was not successfully localized for one patient in the ENB group and three in the CT group. The lesions were fully excised after conversion to mini-thoracotomy. Pathological examination confirmed the accuracy of the dye staining. Analysis found a non-significant difference in the success rate of these two localization methods. However, the following parameters were significantly different: interval between localization to surgery, global time, and rate of pneumothorax (p < 0.05). Conclusions: In the era of minimally invasive surgery, surgeons need an efficient one-step way to manage pulmonary nodules. Patent blue vital injection with ENB guidance in the operating room is a new, effective approach to localize small, deep-seated and non-palpable pulmonary lesions, comparable with CT-guided localization.
Critical Review of the Parameters Affecting the Effectiveness of Moisture Absorption Treatments Used for Natural Composites
Authors: Al-Maharma Ahmad , Al-Huniti Naser
Published: March 2019

Natural composites can be fabricated through reinforcing either synthetic or bio-based polymers with hydrophilic natural fibers. Ultimate moisture absorption resistance at the fiber–matrix interface can be achieved when hydrophilic natural fibers are used to reinforce biopolymers due to the high degree of compatibility between them. However, the cost of biopolymers is several times higher than that of their synthetic counterparts, which hinders their dissemination in various industries. In order to produce economically feasible natural composites, synthetic resins are frequently reinforced with hydrophilic fibers, which increases the incompatibility issues such as the creation of voids and delamination at fiber–matrix interfaces. Therefore, applying chemical and/or physical treatments to eliminate the aforementioned drawbacks is of primary importance. However, it is demonstrated through this review study that these treatments do not guarantee a sufficient improvement of the moisture absorption properties of natural composites, and the moisture treatments should be applied under the consideration of the following parameters: (i) type of hosting matrix; (ii) type of natural fiber; (iii) loading of natural fiber; (iv) the hybridization of natural fibers with mineral/synthetic counterparts; (v) implantation of nanofillers. Complete discussion about each of these parameters is developed through this study.
Visualisation and Analysis of Speech Production with Electropalatography
Authors: Verhoeven Jo , Miller Naomi Rachel , Daems Luc , Reyes-Aldasoro Constantino Carlos
Published: March 2019

The process of speech production, i.e., the compression of air in the lungs, the vibration activity of the larynx, and the movement of the articulators, is of great interest in phonetics, phonology, and psychology. One technique by which speech production is analysed is electropalatography, in which an artificial palate, moulded to the speaker’s hard palate, is introduced in the mouth. The palate contains a grid of electrodes, which monitor the spatial and temporal pattern of contact between the tongue and the palate during speech production. The output is a time sequence of images, known as palatograms, which show the 2D distribution of electrode activation. This paper describes a series of tools for the visualisation and analysis of palatograms and their associated sound signals. The tools are developed as Matlab® routines and released as an open-source toolbox. The particular focus is the analysis of the amount and direction of left–right asymmetry in tongue–palate contact during the production of different speech sounds. Asymmetry in the articulation of speech, as measured by electropalatography, may be related to the language under consideration, the speaker’s anatomy, irregularities in the palate manufacture, or speaker handedness (i.e., left or right). In addition, a pipeline for the segmentation and analysis of a three-dimensional computed tomography data set of an artificial palate is described and demonstrated. The segmentation procedure provides quantitative information about asymmetry that is due to a combination of speaker anatomy (the shape of the hard palate) and the positioning of the electrodes during manufacture of the artificial palate. The tools provided here should be useful in future studies of electropalatography.
Kinematically Coupled Force Compensation—Experimental Results and Advanced Design for the 1D-Implementation
Authors: Ihlenfeldt Steffen , Müller Jens , Merx Marcel , Peukert Christoph
Published: March 2019

Typically, the feed dynamics of machine tools are limited to reduce excitations of machine structure oscillations. Consequently, the potential increase in productivity provided by electrical direct drives cannot be exploited. The novel approach of the Kinematically Coupled Force Compensation (KCFC) combines the principles of redundant axes and force compensation to achieve an increase in the machine’s feed dynamics. Because the drive reaction forces are directly applied to the machine frame, they cancel out each other perfectly if the relative motion at the Tool Centre Point (TCP) is split according to the mass ratio of the slides. In this paper, the principle of KCFC is introduced briefly and possible improvements in the design of machine structures and control are presented. The results of experimental investigations obtained by means of a 1D-KCFC Test Bed illustrate the effectiveness of the principle. Moreover, a further increase of the compensation quality can be achieved by decoupling the force flow from the machine frame, by means of elastic elements. Finally, an outlook on future research with reference to the 1D-implementation as well as possible applications of the KCFC in highly productive processes is given.
Tool Use by Four Species of Indo-Pacific Sea Urchins
Authors: Barrett Glyn A. , Revell Dominic , Harding Lucy , Mills Ian , Jorcin Axelle , Stiefel Klaus M.
Published: March 2019

We compared the covering behavior of four sea urchin species, Tripneustes gratilla, Pseudoboletia maculata, Toxopneustes pileolus, and Salmacis sphaeroides found in the waters of Malapascua Island, Cebu Province and Bolinao, Panagsinan Province, Philippines. Specifically, we measured the amount and type of covering material on each sea urchin, and in several cases, the recovery of debris material after stripping the animal of its cover. We found that Tripneustes gratilla and Salmacis sphaeroides have a higher affinity for plant material, especially seagrass, compared to Pseudoboletia maculata and Toxopneustes pileolus, which prefer to cover themselves with coral rubble and other calcified material. Only in Toxopneustes pileolus did we find a significant corresponding depth-dependent decrease in total cover area, confirming previous work that covering behavior serves as a protection mechanism against UV radiation. We found no dependence of particle size on either species or size of sea urchin, but we observed that larger sea urchins generally carried more and heavier debris. We observed a transport mechanism of debris onto the echinoid body surface utilizing a combination of tube feet and spines. We compare our results to previous studies, comment on the phylogeny of sea urchin covering behavior, and discuss the interpretation of this behavior as animal tool use.
Insomnia: An Important Antecedent Impacting Entrepreneurs’ Health
Authors: Levasseur Ludvig , Tang Jintong , Karami Masoud
Published: March 2019

Insomnia (and sleep deprivation) has an important impact on multiple outcomes such as individuals’ cognitive abilities, decision-making, and affect. In this paper, drawing from sleep research, we focus on entrepreneurs’ insomnia–health relationship and test a serial mediation model that considers entrepreneurs’ insomnia as an important predictor of their poor health. More specifically, we hypothesize that insomnia heightens entrepreneurs’ stress, which leads to increased negative affect, which ultimately undermines their health conditions. Using a sample of 152 Iranian entrepreneurs, we found support for our hypotheses as our results suggest that insomnia has a positive (and detrimental) effect on poor health (via more stress and negative affect). Contrary to research calls focused on stress reduction as one performance improvement mechanism, our results suggest sleep quality as a more effective mechanism for entrepreneurs to reduce their stress and to improve their health. Theoretical and practical implications, limitations, and directions for future research are also discussed.
The Astrophysical Formation of Asymmetric Molecules and the Emergence of a Chiral Bias
Authors: Garcia Adrien D. , Meinert Cornelia , Sugahara Haruna , Jones Nykola C. , Hoffmann Søren V. , Meierhenrich Uwe J.
Published: March 2019

The biomolecular homochirality in living organisms has been investigated for decades, but its origin remains poorly understood. It has been shown that circular polarized light (CPL) and other energy sources are capable of inducing small enantiomeric excesses (ees) in some primary biomolecules, such as amino acids or sugars. Since the first findings of amino acids in carbonaceous meteorites, a scenario in which essential chiral biomolecules originate in space and are delivered by celestial bodies has arisen. Numerous studies have thus focused on their detection, identification, and enantiomeric excess calculations in extraterrestrial matrices. In this review we summarize the discoveries in amino acids, sugars, and organophosphorus compounds in meteorites, comets, and laboratory-simulated interstellar ices. Based on available analytical data, we also discuss their interactions with CPL in the ultraviolet (UV) and vacuum ultraviolet (VUV) regions, their abiotic chiral or achiral synthesis, and their enantiomeric distribution. Without doubt, further laboratory investigations and upcoming space missions are required to shed more light on our potential extraterrestrial molecular origins.
Bactericidal and Biocompatible Properties of Plasma Chemical Oxidized Titanium (TiOB®) with Antimicrobial Surface Functionalization
Authors: Kranz Stefan , Guellmar André , Voelpel Andrea , Lesser Tobias , Tonndorf-Martini Silke , Schmidt Juergen , Schrader Christian , Faucon Mathilde , Finger Ulrich , Pfister Wolfgang , Diefenbeck Michael , Sigusch Bernd
Published: March 2019

Coating of plasma chemical oxidized titanium (TiOB®) with gentamicin-tannic acid (TiOB® gta) has proven to be efficient in preventing bacterial colonization of implants. However, in times of increasing antibiotic resistance, the development of alternative antimicrobial functionalization strategies is of major interest. Therefore, the aim of the present study is to evaluate the antibacterial and biocompatible properties of TiOB® functionalized with silver nanoparticles (TiOB® SiOx Ag) and ionic zinc (TiOB® Zn). Antibacterial efficiency was determined by agar diffusion and proliferation test on Staphylocuccus aureus. Cytocompatibility was analyzed by direct cultivation of MC3T3-E1 cells on top of the functionalized surfaces for 2 and 4 d. All functionalized surfaces showed significant bactericidal effects expressed by extended lag phases (TiOB® gta for 5 h, TiOB® SiOx Ag for 8 h, TiOB® Zn for 10 h). While TiOB® gta (positive control) and TiOB® Zn remained bactericidal for 48 h, TiOB® SiOx Ag was active for only 4 h. After direct cultivation for 4 d, viable MC3T3-E1 cells were found on all surfaces tested with the highest biocompatibility recorded for TiOB® SiOx Ag. The present study revealed that functionalization of TiOB® with ionic zinc shows bactericidal properties that are comparable to those of a gentamicin-containing coating.