bluuebunny/crossref_metadata_2025 huggingface dataset:
International R&D Collaboration for a Global Aging Society: Focusing on Aging-Related National-Funded Projects
Authors: Lee Doyeon , Kim Seungwook , Kim Keunhwan
Published: November 2020

An international research and development (R&D) collaboration for aging-related projects is necessary to alleviate the severe economic/healthcare/humanitarian challenges of a global aging society. This study presents a practical/systematic framework that enables the provision of information on the research goals, the status of science and technology, and action plans of aging-related program development processes. We used data on aging-related national-funded projects from the United States of America, the European Union, the United Kingdom, Japan, and Korea. We collected data on 6318 national-funded projects, subsequently designating research fields to each project. By analyzing the content of the projects, their representative research fields, and the associated keywords, we assessed the general goals of six different research fields. To recognize the current scientific capabilities of these research fields, we divided the projects by clusters. We provided information on research organizations, specific goals (i.e., project title), project periods, and the funding related to the projects. These may be used by stakeholders in various governments/institutions/industries during future discussions regarding the establishment of an international R&D collaboration strategy. The approach we proposed may facilitate the linkage between knowledge and action during strategy development by maximizing scientific legitimacy, developing consensual knowledge, and minimizing diverging opinions among stakeholders.
Workplace Screening Identifies Clinically Significant and Potentially Reversible Kidney Injury in Heat-Exposed Sugarcane Workers
Authors: Sorensen Cecilia J. , Krisher Lyndsay , Butler-Dawson Jaime , Dally Miranda , Dexter Lynn , Asensio Claudia , Cruz Alex , Newman Lee S.
Published: November 2020

An epidemic of chronic kidney disease of unknown origin (CKDu) has emerged in the past two decades in agricultural communities, characterized by progressive renal failure with a dearth of early clinical symptoms. The aim of this study is to improve understanding of the natural history of this disease and to evaluate the impact of an educational and behavioral intervention on the trajectories of renal decline among a cohort of Guatemalan sugarcane workers. We identified groups of workers based on their kidney function during a longitudinal parent study conducted among sugarcane workers during the 2016–2017 harvest season. At the study’s first time point in February 2017, workers who developed abnormal kidney function (AKF) (estimated glomerular filtration rate, eGFR, <60 mL/min per 1.73 m2) were placed in the AKF group, workers with reduced kidney function (RKF) (eGFR 60–89) were placed in the RKF group, and workers who maintained normal kidney function (NKF) (eGFR ≥ 90) were placed in the NKF group. As part of the study, a health promotion, behavioral and educational intervention centered on water, electrolytes, rest, and shade (WERS) was provided to all study participants. We then prospectively analyzed renal function at the three study time points in February, March, and April. Additional data collected from previous harvests allowed for retrospective analysis and we compared the rate of change in eGFR over the previous five years (2012 to 2016) for each identified group. Mixed effects linear regression with random intercepts for the workers was used to investigate the difference in rates of change for the three groups and to assess the impact of the intervention study on rate of change of kidney function during the study compared to each group’s prior trajectory, utilizing the retrospective data collected during the five years prior to the study intervention. Between 2012 and 2016, eGFR declined at a rate of 0.18 mL/min per 1.73 m2 per year for the NKF group (95% CI: −0.66, 0.29, p = 0.45), 2.02 per year for the RKF group (95% CI: 1.00, 3.03, p = 0.0001) and 7.52 per year for the AKF group (95% CI: 6.01, 9.04, p < 0.0001). All study groups stabilized or improved their trajectory of decline during the intervention. This study supports the need to institute WERS interventions and to include mid-harvest screening protocols and longitudinal tracking of kidney function among sugarcane workers at high risk of CKDu. Early detection of rapid kidney function decline combined with appropriate interventions hold promise for stopping or slowing progression of renal insufficiency among these workers.
Repercussion of COVID-19 Pandemic on Brazilians’ Quality of Life: A Nationwide Cross-Sectional Study
Authors: Teotônio Isabella , Hecht Mariana , Castro Luiz Claudio , Gandolfi Lenora , Pratesi Riccardo , Nakano Eduardo Y. , Puppin Zandonadi Renata , Pratesi Claudia B.
Published: November 2020

The COVID-19 outbreak, caused by Sars-Cov-2, was officially declared a global pandemic in February 2020, after an unexpected increase in hospitalization and mortality. When faced with this new disease, social and physical distancing and quarantine emerged as solutions to reduce virus transmission. This article examines the quality of life (QoL) of the Brazilian population’s during this period of isolation, due to the COVID-19 pandemic by analyzing; physical, psychological, social, and economic aspects. An online survey was distributed from 27 May to 14 August of 2020. A total of 1859 surveys were completed. Our results indicate that Brazilians were more affected by economic and social aspects than psychological and physical. Unemployed participants and individuals who tested positive for COVID-19 presented the lowest QoL. Females showed worst QoL scores than males, but having children did not influence the score. Higher educational level was associated with a better perception of QoL. Not following social distancing guidelines presented better scores in the psychological domain than the ones following restrict or partial social distancing rules. This study is the first to evaluate adults’ QoL related to the Sars-Cov-2 pandemic in Brazil at a national level. Our data may help health authorities identify the main factors affecting the QoL of the Brazilian population, thereby orientating them to recover after the pandemic.
The Effect of Ethiopia’s Community-Based Health Insurance Scheme on Revenues and Quality of Care
Authors: Shigute Zemzem , Mebratie Anagaw D. , Sparrow Robert , Alemu Getnet , Bedi Arjun S.
Published: November 2020

Ethiopia’s Community-Based Health Insurance (CBHI) scheme was established with the objectives of enhancing access to health care, reducing out-of-pocket expenditure (OOP), mobilizing financial resources and enhancing the quality of health care. Previous analyses have shown that the scheme has enhanced health care access and led to reductions in OOP. This paper examines the impact of the scheme on health facility revenues and quality of care. This paper relies on a difference-in-differences approach applied to both panel and cross-section data. We find that CBHI-affiliated facilities experience a 111% increase in annual outpatient visits and annual revenues increase by 47%. Increased revenues are used to ameliorate drug shortages. These increases have translated into enhanced patient satisfaction. Patient satisfaction increased by 11 percentage points. Despite the increase in patient volume, there is no discernible increase in waiting time to see medical professionals. These results and the relatively high levels of CBHI enrollment suggest that the Ethiopian CBHI has been able to successfully negotiate the main stumbling block—that is, the poor quality of care—which has plagued similar CBHI schemes in Sub-Saharan Africa.
Associations between Poor Vision, Vision-Related Behaviors and Mathematics Achievement in Chinese Students from the CNAEQ-PEH 2015
Authors: Wang Sijia , Hao Xingjie , Ma Xiao , Yu Yong , Wu Lili , Wang Yan , Li Youfa
Published: November 2020

Purpose: Poor vision is prevalent in school-aged students, especially in East Asia. This can not only cause irreversibly physical health impairments like glaucoma and cataracts, but also the loss of individual education and employment opportunities and deterioration of the quality of life. The present study aims to investigate the associations between poor vision, vision-related risk behaviors, and mathematics achievement in youth from China. Methods: The present study included a total of 106,192 Grade 4 students and 70,236 Grade 8 students from the China National Assessment of Educational Quality-Physical Education & Health 2015 (CNAEQ-PEH 2015). We conducted a standard logarithmic visual acuity scale for vision screening, a self-reported questionnaire for vision-related risk behavior and a standardized mathematics assessment for mathematics performance. Poor vision is defined as the visual acuity below 5.0 by using the standard logarithmic visual acuity chart. Linear regression was conducted. Results: The prevalence rate of poor vision in China was 37.1% in Grade 4 and 66.2% in Grade 8 in 2015. Students who had poor vision were more likely to have better mathematics achievement than those with normal vision. Reading in bed, insufficient sleep, and screen time during weekdays and weekends were associated with higher odds of poor vision. Conclusions: Poor vision was positively associated with mathematics academic achievements, while vision-related risk behaviors such as screen time, homework time and reading in bed were associated with a high prevalence of poor vision in compulsory education cycle students.
Prevalence and Associated Factors of Self-Reported Gingival Bleeding: A Multicenter Study in France
Authors: Veynachter Thomas , Orti Valérie , Moulis Estelle , Rousseau Hélène , Thilly Nathalie , Anagnostou Fani , Jeanne Sylvie , Bisson Catherine
Published: November 2020

Gingival bleeding (GB) is a common sign of gingival inflammation which indicates the presence of periodontal diseases. This cross-sectional multicenter survey aimed to assess the prevalence of self-reported gingival bleeding (SRGB) in French adults and identify the main associated factors. A questionnaire-based interview was randomly proposed to 794 individuals in four French cities (Nancy, Montpellier, Paris, and Rennes). Subjects were recruited in preventive medicine centers (50%), railway stations, and malls (50%). The questionnaire comprised 25 items: SRGB characteristics, socioeconomic variables, oral hygiene habits, use of drugs, and anxiety level. The overall prevalence of SRGB was 63.2% [59.8%; 66.6%], with 58.7% bleeding after toothbrushing and 4.5% spontaneous bleeding. Males reported significantly lower SRGB prevalence than females (p = 0.04). The distribution of SRGB frequency was inversely proportional to age (p < 0.0001). No association between drug use and SRGB was found. The people interviewed in the preventive medicine centers reported the highest frequency of SRGB (p < 0.0001). In the multivariate logistic model, SRGB was significantly related to occupation, smoking status, brushing frequency, and anxiety level. In conclusion, SRGB was prevalent in more than half of the sample and was mainly associated with age, toothbrushing frequency, and anxiety level. Thus, providing information to patients about the importance of this oral manifestation may play an important role in preventing periodontal diseases.
Is Weight Gain Inevitable for Patients Trying to Quit Smoking as Part of Cardiac Rehabilitation?
Authors: Salman Ahmad , Doherty Patrick
Published: November 2020

The literature is uncertain about the extent to which those who attend cardiac rehabilitation (CR) gain weight while trying to quit smoking. This study aimed to determine the extent of CR-based smoking cessation provision and whether CR, as delivered in routine practice, is associated with helping patients quit smoking and avoid weight gain. Data from the UK National Audit of Cardiac Rehabilitation database, between April 2013 and March 2016, were used. Smoking status is categorised as smokers and quitters assessed by patient self-report. Outcomes included body weight, blood pressure, depression, and physical activity. A multiple linear regression model was constructed to understand the effect of continuing smoking or quitting smoking on CR outcomes. CR outcome scores were adjusted by the baseline CR score for each characteristic. An e-survey collected information about the smoking cessation support offered to patients attending CR. A total of 2052 smokers (58.59 ± 10.49 years, 73.6% male) and 1238 quitters (57.63 ± 10.36 years, 75.8% male) were analysed. Overall, 92.6% of CR programmes in the United Kingdom (UK) offer smoking cessation support for CR attenders. Quitting smoking during CR was associated with a mean increase in body weight of 0.4 kg, which is much less than seen in systematic reviews. Quitters who attended CR also had better improvements in physical activity status and psychosocial health measures than smokers. As delivered in routine practice, CR programmes in the UK adhere to the guideline recommendations for smoking cessation interventions, help patients quit smoking, and avoid weight gain on completion of CR.
Corporate Social Responsibility and Firm Value Protection
Authors: Ogachi Daniel , Zoltan Zeman
Published: November 2020

The conception of Corporate Social Responsibility has continued to gain a lengthy discussion in all aspects of corporate finance with a particular focus on its contributing to financial performance. Despite its prominence globally, many companies have not embraced the concept, as most of them have remained doubtful about its contribution to corporate financial performance. Several companies have digressed the idea to merely an aspect of charity and cost instead of cost reduction and market creation. The fixed-effect model of panel data analysis was applied for the study period from 2010 to 2019 to measure relationships on CSR’s effect on the financial performance of listed companies in Kenya. The study used panel data for the years 2010–2019. The research used trend analysis for ten years to analyse data using canonical correlations, Logistic Regression analysis and ARIMA models to establish relationships among the variables of the study. Our results offer new evidence on the linearity effect of CSR on financial performance suggest that Corporate Social Responsibilities activities are very vital influencers of firm value, as they have a positive influence on the financial performance of companies.
Multi-View Instance Matching with Learned Geometric Soft-Constraints
Authors: Nassar Ahmed Samy , Lefèvre Sébastien , Wegner Jan Dirk
Published: November 2020

We present a new approach for matching urban object instances across multiple ground-level images for the ultimate goal of city-scale mapping of objects with high positioning accuracy. What makes this task challenging is the strong change in view-point, different lighting conditions, high similarity of neighboring objects, and variability in scale. We propose to turn object instance matching into a learning task, where image-appearance and geometric relationships between views fruitfully interact. Our approach constructs a Siamese convolutional neural network that learns to match two views of the same object given many candidate image cut-outs. In addition to image features, we propose utilizing location information about the camera and the object to support image evidence via soft geometric constraints. Our method is compared to existing patch matching methods to prove its edge over state-of-the-art. This takes us one step closer to the ultimate goal of city-wide object mapping from street-level imagery to benefit city administration.
Diabetes Mellitus Is a Chronic Disease that Can Benefit from Therapy with Induced Pluripotent Stem Cells
Authors: Arroyave Felipe , Montaño Diana , Lizcano Fernando
Published: November 2020

Diabetes mellitus (DM) is one of the main causes of morbidity and mortality, with an increasing incidence worldwide. The impact of DM on public health in developing countries has triggered alarm due to the exaggerated costs of the treatment and monitoring of patients with this disease. Considerable efforts have been made to try to prevent the onset and reduce the complications of DM. However, because insulin-producing pancreatic β-cells progressively deteriorate, many people must receive insulin through subcutaneous injection. Additionally, current therapies do not have consistent results regarding the prevention of chronic complications. Leveraging the approval of real-time continuous glucose monitors and sophisticated algorithms that partially automate insulin infusion pumps has improved glycemic control, decreasing the burden of diabetes management. However, these advances are facing physiologic barriers. New findings in molecular and cellular biology have produced an extraordinary advancement in tissue development for the treatment of DM. Obtaining pancreatic β-cells from somatic cells is a great resource that currently exists for patients with DM. Although this therapeutic option has great prospects for patients, some challenges remain for this therapeutic plan to be used clinically. The purpose of this review is to describe the new techniques in cell biology and regenerative medicine as possible treatments for DM. In particular, this review highlights the origin of induced pluripotent cells (iPSCs) and how they have begun to emerge as a regenerative treatment that may mitigate the pathology of this disease.
Impaired Expression of GABA Signaling Components in the Alzheimer’s Disease Middle Temporal Gyrus
Authors: Govindpani Karan , Turner Clinton , Waldvogel Henry J. , Faull Richard L. M. , Kwakowsky Andrea
Published: November 2020

γ-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter, playing a central role in the regulation of cortical excitability and the maintenance of the excitatory/inhibitory (E/I) balance. Several lines of evidence point to a remodeling of the cerebral GABAergic system in Alzheimer’s disease (AD), with past studies demonstrating alterations in GABA receptor and transporter expression, GABA synthesizing enzyme activity and focal GABA concentrations in post-mortem tissue. AD is a chronic neurodegenerative disorder with a poorly understood etiology and the temporal cortex is one of the earliest regions in the brain to be affected by AD neurodegeneration. Utilizing NanoString nCounter analysis, we demonstrate here the transcriptional downregulation of several GABA signaling components in the post-mortem human middle temporal gyrus (MTG) in AD, including the GABAA receptor α1, α2, α3, α5, β1, β2, β3, δ, γ2, γ3, and θ subunits and the GABAB receptor 2 (GABABR2) subunit. In addition to this, we note the transcriptional upregulation of the betaine-GABA transporter (BGT1) and GABA transporter 2 (GAT2), and the downregulation of the 67 kDa isoform of glutamate decarboxylase (GAD67), the primary GABA synthesizing enzyme. The functional consequences of these changes require further investigation, but such alterations may underlie disruptions to the E/I balance that are believed to contribute to cognitive decline in AD.
Discovery and Design of Novel Small Molecule GSK-3 Inhibitors Targeting the Substrate Binding Site
Authors: Rippin Ido , Khazanov Netaly , Ben Joseph Shirley , Kudinov Tania , Berent Eva , Arciniegas Ruiz Sara Melisa , Marciano Daniele , Levy Laura , Gruzman Arie , Senderowitz Hanoch , Eldar-Finkelman Hagit
Published: November 2020

The serine/threonine kinase, GSK-3, is a promising drug discovery target for treating multiple pathological disorders. Most GSK-3 inhibitors that were developed function as ATP competitive inhibitors, with typical limitations in specificity, safety and drug-induced resistance. In contrast, substrate competitive inhibitors (SCIs), are considered highly selective, and more suitable for clinical practice. The development of SCIs has been largely neglected in the past because the ambiguous, undefined nature of the substrate-binding site makes them difficult to design. In this study, we used our previously described structural models of GSK-3 bound to SCI peptides, to design a pharmacophore model and to virtually screen the “drug-like” Zinc database (~6.3 million compounds). We identified leading hits that interact with critical binding elements in the GSK-3 substrate binding site and are chemically distinct from known GSK-3 inhibitors. Accordingly, novel GSK-3 SCI compounds were designed and synthesized with IC50 values of~1–4 μM. Biological activity of the SCI compound was confirmed in cells and in primary neurons that showed increased β-catenin levels and reduced tau phosphorylation in response to compound treatment. We have generated a new type of small molecule GSK-3 inhibitors and propose to use this strategy to further develop SCIs for other protein kinases.
Photodynamic Inactivation of Bacteria with Porphyrin Derivatives: Effect of Charge, Lipophilicity, ROS Generation, and Cellular Uptake on Their Biological Activity In Vitro
Authors: Sułek Adam , Pucelik Barbara , Kobielusz Marcin , Barzowska Agata , Dąbrowski Janusz M.
Published: November 2020

Resistance of microorganisms to antibiotics has led to research on various therapeutic strategies with different mechanisms of action, including photodynamic inactivation (PDI). In this work, we evaluated a cationic, neutral, and anionic meso-tetraphenylporphyrin derivative’s ability to inactivate the Gram-negative and Gram-positive bacteria in a planktonic suspension under blue light irradiation. The spectroscopic, physicochemical, redox properties, as well as reactive oxygen species (ROS) generation capacity by a set of photosensitizers varying in lipophilicity were investigated. The theoretical calculations were performed to explain the distribution of the molecular charges in the evaluated compounds. Moreover, logP partition coefficients, cellular uptake, and phototoxicity of the photosensitizers towards bacteria were determined. The role of a specific microbial efflux pump inhibitor, verapamil hydrochloride, in PDI was also studied. The results showed that E. coli exhibited higher resistance to PDI than S. aureus (3–5 logs) with low light doses (1–10 J/cm2). In turn, the prolongation of irradiation (up to 100 J/cm2) remarkably improved the inactivation of pathogens (up to 7 logs) and revealed the importance of photosensitizer photostability. The PDI potentiation occurs after the addition of KI (more than 3 logs extra killing). Verapamil increased the uptake of photosensitizers (especially in E. coli) due to efflux pump inhibition. This effect suggests that PDI is mediated by ROS, the electrostatic charge interaction, and the efflux of photosensitizers (PSs) regulated by multidrug-resistance (MDR) systems. Thus, MDR inhibition combined with PDI gives opportunities to treat more resistant bacteria.
Mechanistic Insights into Synergy between Melanin-Targeting Radioimmunotherapy and Immunotherapy in Experimental Melanoma
Authors: Malo Mackenzie E. , Allen Kevin J. H. , Jiao Rubin , Frank Connor , Rickles David , Dadachova Ekaterina
Published: November 2020

Melanoma incidence continues to rise, and while therapeutic approaches for early stage cases are effective, metastatic melanoma continues to be associated with high mortality. Immune checkpoint blockade (ICB) has demonstrated clinical success with approved drugs in cohorts of patients with metastatic melanoma and targeted radionuclide therapy strategies showed promise in several clinical trials against various cancers including metastatic melanoma. This led our group to investigate the combination of these two treatments which could be potentially offered to patients with metastatic melanoma not responsive to ICB alone. Previously, we have demonstrated that a combination of humanized anti-melanin antibody conjugated to 213Bismuth and anti-PD-1 ICB reduced tumor growth and increased survival in the Cloudman S91 murine melanoma DBA/2 mouse model. In the current study, we sought to improve the tumoricidal effect by using the long-lived radionuclides 177Lutetium and 225Actinium. Male Cloudman S91-bearing DBA/2 mice were treated intraperitoneally with PBS (Sham), unlabeled antibody to melanin, anti-PD-1 ICB, 177Lutetium or 225Actinium RIT, or a combination of ICB and RIT. Treatment with anti-PD-1 alone or low-dose 177Lutetium RIT alone resulted in modest tumor reduction, while their combination significantly reduced tumor growth and increased survival, suggesting synergy. 225Actinium RIT, alone or in combination with ICB, showed no therapeutic benefit, suggesting that the two radionuclides with different energetic properties work in distinct ways. We did not detect an increase in tumor-infiltrating T cells in the tumor microenvironment, which suggests the involvement of alternative mechanisms that improve the effect of combination therapy beyond that observed in the single therapies.
Search for Alternative Control Strategies of Drosophila suzukii (Diptera: Drosophilidae): Laboratory Assays Using Volatile Natural Plant Compounds
Authors: Eben Astrid , Sporer Frank , Vogt Heidrun , Wetterauer Pille , Wink Michael
Published: November 2020

Drosophila suzukii (Diptera: Drosophilidae), is native to southeastern Asia and invaded Europe during the past decade. It causes serious economic damage in cherries and soft fruits. Control strategies rely on few insecticides with varying success. Due to environmental concern, the use of synthetic chemicals is restricted. Therefore, research effort is put into the quest for alternative substances applicable in chemical pest control. In laboratory assays, we tested 17 volatile plant compounds from different chemical classes for their contact toxicity, feeding modification, and oviposition repellency. Toxicity through contact with treated surfaces was evaluated after 1 h, 4 h, and 24 h; effects on food uptake were observed with capillary feeding (CAFE)—tests and oviposition trials compared egg numbers laid in raspberry medium with or without treated filter paper. Cinnamon oil and its components had the highest contact toxicity with an LC90 = 2–3%, whereas lemongrass oil, its main components, and farnesol were less toxic (LC90 = 7–9%), and geraniol was the least toxic. In CAFE tests, feeding stimulation was observed through 0.1% and 1% solutions of citronellol, lemongrass oil and farnesol. Cinnamon oil, cinnamaldhyde, and ethyl cinnamate were not consumed at a concentration of 1%. In the presence of citral, eugenol, and lemongrass oil, oviposition was reduced, and in the presence of limonene, no eggs were deposited. The natural products found most efficient in either bioassay will be further tested under field conditions.
What Is the Spatial Extent of a Bemisia tabaci Population?
Authors: Crossley Michael S. , Snyder William E.
Published: November 2020

Effective pest management depends on basic knowledge about insect dispersal patterns and gene flow in agroecosystems. The globally invasive sweet potato whitefly Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) is considered a weak flier whose life history nonetheless predisposes it to frequent dispersal, but the scale over which populations exchange migrants, and should therefore be managed, is uncertain. In this review, we synthesize the emergent literature on B. tabaci population genetics to address the question: What spatial scales define B. tabaci populations? We find that within-species genetic differentiation among sites is often low, and evidence of population structuring by host plant or geography is rare. Heterozygote deficits prevail among populations, indicating that migrants from divergent populations are frequently sampled together. Overall, these results suggest that there is high ongoing gene flow over large spatial extents. However, genetic homogeneity typical of recently invading populations could obscure power to detect real isolation among populations. Genome-wide data collected systematically across space and time could distinguish signatures of invasion history from those of ongoing gene flow. Characterizing the spatial extent of B. tabaci populations could reveal whether insecticide rotations can be tailored to specific commodities or if coordination across linked commodities and regions is justified.
Co-Expression of Coxsackievirus/Adenovirus Receptors and Desmoglein 2 in Lung Adenocarcinoma: A Comprehensive Analysis of Bioinformatics and Tissue Microarrays
Authors: Weng Ching-Fu , Huang Chi-Jung , Wu Mei-Hsuan , Lee Henry Hsin-Chung , Ling Thai-Yen
Published: November 2020

Introduction: Coxsackievirus/adenovirus receptors (CARs) and desmoglein-2 (DSG2) are similar molecules to adenovirus-based vectors in the cell membrane. They have been found to be associated with lung epithelial cell tumorigenesis and can be useful markers in predicting survival outcome in lung adenocarcinoma (LUAD). Methods: A gene ontology enrichment analysis disclosed that DSG2 was highly correlated with CAR. Survival analysis was then performed on 262 samples from the Cancer Genome Atlas, forming “Stage 1A” or “Stage 1B”. We therefore analyzed a tissue microarray (TMA) comprised of 108 lung samples and an immunohistochemical assay. Computer counting software was used to calculate the H-score of the immune intensity. Cox regression and Kaplan–Meier analyses were used to determine the prognostic value. Results: CAR and DSG2 genes are highly co-expressed in early stage LUAD and associated with significantly poorer survival (p = 0.0046). TMA also showed that CAR/DSG2 expressions were altered in lung cancer tissue. CAR in the TMA was correlated with proliferation, apoptosis, and epithelial–mesenchymal transition (EMT), while DSG2 was associated with proliferation only. The Kaplan–Meier survival analysis revealed that CAR, DSG2, or a co-expression of CAR/DSG2 was associated with poorer overall survival. Conclusions: The co-expression of CAR/DSG2 predicted a worse overall survival in LUAD. CAR combined with DSG2 expression can predict prognosis.
Driver Mutations and Single Copy Number Abnormalities Identify Binet Stage A Patients with Chronic Lymphocytic Leukemia with Aggressive Progression
Authors: Gonzalez-Rodriguez Ana P. , Payer Angel R. , Menendez-Suarez Juan J. , Sordo-Bahamonde Christian , Lorenzo-Herrero Seila , Zanabili Joud , Fonseca Ariana , Gonzalez-Huerta Ana Julia , Palomo Pilar , Gonzalez Segundo
Published: November 2020

The correlation between progression and the genetic characteristics of Binet stage A patients with chronic lymphocytic leukemia (CLL) detected by whole exome sequencing (WES) was analyzed in 55 patients. The median follow-up for the patients was 102 months. During the follow-up, 24 patients (43%) progressed. Univariate Cox analysis showed that the presence of driver mutations, the accumulation of two or more mutations, the presence of adverse mutations, immunoglobulin heavy chain genes (IGHV) mutation status and unfavorable single copy number abnormalities (SCNAs) were associated with a higher risk of progression. Particularly, the occurrence of an adverse mutation and unfavorable SCNAs increased the risk of progression nine-fold and five-fold, respectively. Nevertheless, only the occurrence of adverse mutations retained statistical significance in the multivariate analysis. All patients carrying an unfavorable mutation progressed with a median progression-free survival (PFS) of 29 months. The accumulation of two or more mutations also increased the risk of progression with a median PFS of 29 months. The median PFS of patients with unfavorable SCNAs was 38 months. Combining mutations and SCNAs, patients may be stratified into three groups with different prognostic outcomes: adverse (17% probability of five-year PFS), protective (86% probability of five-year PFS) and neither (62% probability of five-year PFS, p < 0.001). Overall, the analysis of the mutational status of patients with CLL at an early stage of the disease may allow the identification of patients with a high risk of progression. The feasibility of an early therapeutic intervention in these particular patients requires further investigation.
Digital Pathology: Advantages, Limitations and Emerging Perspectives
Authors: Jahn Stephan W. , Plass Markus , Moinfar Farid
Published: November 2020

Digital pathology is on the verge of becoming a mainstream option for routine diagnostics. Faster whole slide image scanning has paved the way for this development, but implementation on a large scale is challenging on technical, logistical, and financial levels. Comparative studies have published reassuring data on safety and feasibility, but implementation experiences highlight the need for training and the knowledge of pitfalls. Up to half of the pathologists are reluctant to sign out reports on only digital slides and are concerned about reporting without the tool that has represented their profession since its beginning. Guidelines by international pathology organizations aim to safeguard histology in the digital realm, from image acquisition over the setup of work-stations to long-term image archiving, but must be considered a starting point only. Cost-efficiency analyses and occupational health issues need to be addressed comprehensively. Image analysis is blended into the traditional work-flow, and the approval of artificial intelligence for routine diagnostics starts to challenge human evaluation as the gold standard. Here we discuss experiences from past digital pathology implementations, future possibilities through the addition of artificial intelligence, technical and occupational health challenges, and possible changes to the pathologist’s profession.
Helicobacter pylori-Mediated Immunity and Signaling Transduction in Gastric Cancer
Authors: Ito Nozomi , Tsujimoto Hironori , Ueno Hideki , Xie Qian , Shinomiya Nariyoshi
Published: November 2020

Helicobacter pylori infection is a leading cause of gastric cancer, which is the second-most common cancer-related death in the world. The chronic inflammatory environment in the gastric mucosal epithelia during H. pylori infection stimulates intracellular signaling pathways, namely inflammatory signals, which may lead to the promotion and progression of cancer cells. We herein report two important signal transduction pathways, the LPS-TLR4 and CagA-MET pathways. Upon H. pylori stimulation, lipopolysaccharide (LPS) binds to toll-like receptor 4 (TLR4) mainly on macrophages and gastric epithelial cells. This induces an inflammatory response in the gastric epithelia to upregulate transcription factors, such as NF-κB, AP-1, and IRFs, all of which contribute to the initiation and progression of gastric cancer cells. Compared with other bacterial LPSs, H. pylori LPS has a unique function of inhibiting the mononuclear cell (MNC)-based production of IL-12 and IFN-γ. While this mechanism reduces the degree of inflammatory reaction of immune cells, it also promotes the survival of gastric cancer cells. The HGF/SF-MET signaling plays a major role in promoting cellular proliferation, motility, migration, survival, and angiogenesis, all of which are essential factors for cancer progression. H. pylori infection may facilitate MET downstream signaling in gastric cancer cells through its CagA protein via phosphorylation-dependent and/or phosphorylation-independent pathways. Other signaling pathways involved in H. pylori infection include EGFR, FAK, and Wnt/β-Catenin. These pathways function in the inflammatory process of gastric epithelial mucosa, as well as the progression of gastric cancer cells. Thus, H. pylori infection-mediated chronic inflammation plays an important role in the development and progression of gastric cancer.
Amoebae in Chronic, Polymicrobial Endodontic Infections Are Associated with Altered Microbial Communities of Increased Virulence
Authors: Koller Garrit , Foschi Federico , Mitchell Philip , Witherden Elizabeth , Bruce Kenneth , Mannocci Francesco
Published: November 2020

Background: Infections of the root canal space involve polymicrobial biofilms and lead to chronic, low grade inflammatory responses arising from the seeding of microbes and by-products. Acute exacerbation and/or disseminating infections occur when established microbial communities undergo sudden changes in phenotypic behaviour. Methods: Within clinical endodontic infections, we assessedcategorical determinants comprising, and changing microbial composition of, chronic polymicrobial infections and their association with amoebae. After standardised assessment, primary or secondary infections underwent sampling and DNA processing, targeting bacteria, fungi and amoebae, including 16S high-throughput sequencing. After taxonomic assignment, community composition was correlated with clinical signs and symptoms. Diversity and abundance analyses were carried out in relation to the presence of non-bacterial amplicons. Results: Clinical specimens revealed two distinct community clusters, where specific changes correlated with clinical signs. An association between the compositions of microbiomes was found between these groups and the presence of Entamoeba gingivalis in 44% of cases. When amoebae were present in endodontic infections, we demonstrate changes in microbial community structure that mirror those observed in treatment-resistant or recurrent infections. Conclusions: Amoeba are present in endodontic infections at a high prevalence, and may promote increased virulence by enrichment for phagocytosis-resistant bacteria.
Evaluation of the Effects of the Enriched-Organic Diets Composition on European Sea Bass Welfare through a Multi-Parametric Approach
Authors: Carbonara Pierluigi , Zupa Walter , Bitetto Isabella , Alfonso Sébastien , Dara Mariano , Cammarata Matteo
Published: November 2020

Three groups of European sea bass (Dicentrarchus labrax) were fed for seven months, with either a conventional diet or two different organic diets, which contain organic vegetables and a natural antioxidant compound. The two organic diets differed themselves in terms of raw proteins, fish oil, and lipid contents. Sea bass welfare condition was assessed in relation to these three diets, using 16 different indicators. These were: swimming activity (recovery test, muscle activity), haematological and serological stress indicators (haematocrit, haemoglobin, red-blood-cell count, cortisol, glucose, lactate), aspecific immunity parameter (lysozyme), indicators of exposure to organic contaminants (7-ethoxyresorufin-O-deethylase and glutathione-S-transferase), and growth parameters (weight gain, specific growth rate, feed conversion ratio, protein efficiency ratio, and hepato-somatic index). Most of these parameters individually did not give consistent responses, but their integration can provide an accurate evaluation of the fish welfare conditions among the three diet experimental groups. The multiparametric approach outlined a comprehensive picture of sea bass physiological state. The principal component analysis and the multi-criteria-decision-analysis were found to be useful tools for an integrated fish welfare assessment, highlighting that the best welfare condition was achieved in the experimental group fed with the protein-rich organic diet.
Isolation, Identification, and Biochemical Characteristics of a Cold-Tolerant Chlorella vulgaris KNUA007 Isolated from King George Island, Antarctica
Authors: Jo Seung-Woo , Do Jeong-Mi , Kang Nam Seon , Park Jong Myong , Lee Jae Hak , Kim Han Soon , Hong Ji Won , Yoon Ho-Sung
Published: November 2020

A cold-tolerant unicellular green alga was isolated from a meltwater stream on King George Island, Antarctica. Morphological, molecular, and biochemical analyses revealed that the isolate belonged to the species Chlorella vulgaris. We tentatively named this algal strain C.vulgaris KNUA007 and investigated its growth and lipid composition. We found that the strain was able to thrive in a wide range of temperatures, from 5 to 30 °C; however, it did not survive at 35 °C. Ultimate analysis confirmed high gross calorific values only at low temperatures (10 °C), with comparable values to land plants for biomass fuel. Gas chromatography/mass spectrometry analysis revealed that the isolate was rich in nutritionally important polyunsaturated fatty acids (PUFAs). The major fatty acid components were hexadecatrienoic acid (C16:3 ω3, 17.31%), linoleic acid (C18:2 ω6, 8.52%), and α-linolenic acid (C18:3 ω3, 43.35%) at 10 °C. The microalga was tolerant to low temperatures, making it an attractive candidate for the production of biochemicals under cold weather conditions. Therefore, this Antarctic microalga may have potential as an alternative to fish and/or plant oils as a source of omega-3 PUFA. The temperature tolerance and composition of C.vulgaris KNUA007 also make the isolate desirable for commercial applications in the pharmaceutical industry.
Biosynthesis of Silver Nanoparticles Using Onion Endophytic Bacterium and Its Antifungal Activity against Rice Pathogen Magnaporthe oryzae
Authors: Ibrahim Ezzeldin , Luo Jinyan , Ahmed Temoor , Wu Wenge , Yan Chenqi , Li Bin
Published: November 2020

Biosynthesis of silver nanoparticles (AgNPs) using endophytic bacteria is a safe alternative to the traditional chemical method. The purpose of this research is to biosynthesize AgNPs using endophytic bacterium Bacillus endophyticus strain H3 isolated from onion. The biosynthesized AgNPs with sizes from 4.17 to 26.9 nm were confirmed and characterized by various physicochemical techniques such as Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), UV-visible spectroscopy, transmission electron microscopy (TEM) and scanning electron microscopy (SEM) in addition to an energy dispersive spectrum (EDS) profile. The biosynthesized AgNPs at a concentration of 40 μg/mL had a strong antifungal activity against rice blast pathogen Magnaporthe oryzae with an inhibition rate of 88% in mycelial diameter. Moreover, the biosynthesized AgNPs significantly inhibited spore germination and appressorium formation of M. oryzae. Additionally, microscopic observation showed that mycelia morphology was swollen and abnormal when dealing with AgNPs. Overall, the current study revealed that AgNPs could protect rice plants against fungal infections.
Evaluation of the Role of Circulating Tumor Cells and Microsatellite Instability Status in Predicting Outcome of Advanced CRC Patients
Authors: Messaritakis Ippokratis , Sfakianaki Maria , Vogiatzoglou Konstantinos , Koulouridi Asimina , Koutoulaki Chara , Mavroudis Dimitrios , Tzardi Maria , Gouvas Nikolaos , Tsiaoussis John , Souglakos John
Published: November 2020

Colorectal cancer (CRC) remains one of the leading causes of cancer-related death due to its high metastatic potential. This study aimed to investigate the detection and heterogeneity of circulating tumor cells (CTCs) and the microsatellite instability (MSI) status in advanced CRC patients prior to any systemic front-line treatment. Peripheral whole blood was obtained from 198 patients. CTCs were detected using double immunofluorescence and a real time-polymerase chain reaction assay; whereas MSI status was evaluated using fragment analysis. Median age of the patients was 66 years, 63.1% were males, 65.2% had a colon/sigmoid tumor location and 90.4% had a good performance status (PS). MSI-High status was detected in 4.9% of the patients; 33.3%, 56.1% and 8.6% patients had at least one detectable CEACAM5+/EpCAM+, CEACAM5+/EpCAM− and CEACAM5−/EpCAM+ CTC, respectively, and 9.1% of the patients had CEACAM5mRNA-positive CTCs. Following multivariate analysis, age, PS and MSI were confirmed as independent prognostic factors for decreased time to progression, whereas age, PS and CTC presence were confirmed as independent prognostic factors for decreased overall survival. In conclusion, our data support the use of CEACAM5 as a dynamic adverse prognostic CTC biomarker in patients with metastatic CRC and MSI-High is considered an unfavorable prognostic factor in metastatic CRC patient tumors.
Planosol CO2 Respiration, Chemical and Physical Properties of Differently Tilled Faba Bean Cultivation
Authors: Kimbirauskienė Rasa , Romaneckas Kęstutis , Naujokienė Vilma , Sinkevičienė Aušra , Šarauskis Egidijus , Buragienė Sidona , Bielski Stanisław
Published: November 2020

Soil tillage intensity influences the chemical composition of soil, the distribution of nutrients, and soil physical and mechanical properties, as well as gas flows. The impact of reduced tillage on these indices in faba bean cultivation is still insufficient and requires more analysis on a global scale. This study was carried out at Vytautas Magnus University, Agriculture Academy (Lithuania) in 2016–2018. The aim of the investigation was to establish the influence of the tillage systems on the soil chemical composition, temperature, moisture content, and CO2 respiration in faba bean cultivation limited by the semi-humid subarctic climate. On the basis of a long-term tillage experiment, five tillage systems were tested: deep and shallow moldboard plowing, deep cultivation-chiseling, shallow cultivation-disking, and no-tillage. Results showed that in conditions of plowless tillage systems, the content of precrops’ residues on the topsoil before the spring tillage was 5 to 15 times higher than in plowed plots. It undoubtedly was for the amount of available nutrients in the soil, soil temperature, and moisture content. Plowless and no-tillage systems could initiate an increase in the amount of available nutrients in soil. The highest concentration of chemical elements was found in no-tilled plots. So faba bean crops could largely increase the composition of potassium and total nitrogen and stabilized CO2 respiration from soil during one vegetative period.
Bioenergy Potential and Greenhouse Gas Emissions from Intensifying European Temporary Grasslands
Authors: Wicke Birka , Kluts Ingeborg , Lesschen Jan Peter
Published: November 2020

Agricultural intensification is considered essential for meeting growing demand for food and biomass for energy purposes. Intensifying grasslands is under-represented, although it is a promising option given their large land area and relatively low management levels. This study quantifies the bioenergy potential from intensifying temporary grasslands in Europe and the integral greenhouse gas emission effects in 2030. We first conducted a literature review of intensification options for European grasslands and then applied the environmental impact assessment model MITERRA-Europe to implement the key intensification option of using multi-species grass mixtures. The results showed that 853 kha (or 8%) of temporary grassland could be made sustainably available for additional biomass production. This can be translated into a bioethanol potential of 23 PJ yr−1 and an emission mitigation potential of 5.8 Mt CO2-eq yr−1 (if conventional grass mixture from surplus temporary grassland is used for energy) or 72 PJ yr−1 and 4.0 Mt CO2-eq yr−1 (if surplus temporary grassland is used for grassy energy crops). Although the bioenergy potential is limited, the key advantage of intensification measure is that it results in a better environmental performance of temporary grasslands. This makes it a key option for sustainably producing bioenergy in areas with high shares of temporary grasslands.