bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational Analysis of the Global Effects of Ly6E in the Immune Response to Coronavirus Infection Using Gene Networks
Authors: Delgado-Chaves Fernando M. , Gómez-Vela Francisco , Divina Federico , García-Torres Miguel , Rodriguez-Baena Domingo S.
Published: July 2020

Gene networks have arisen as a promising tool in the comprehensive modeling and analysis of complex diseases. Particularly in viral infections, the understanding of the host-pathogen mechanisms, and the immune response to these, is considered a major goal for the rational design of appropriate therapies. For this reason, the use of gene networks may well encourage therapy-associated research in the context of the coronavirus pandemic, orchestrating experimental scrutiny and reducing costs. In this work, gene co-expression networks were reconstructed from RNA-Seq expression data with the aim of analyzing the time-resolved effects of gene Ly6E in the immune response against the coronavirus responsible for murine hepatitis (MHV). Through the integration of differential expression analyses and reconstructed networks exploration, significant differences in the immune response to virus were observed in Ly6E Δ H S C compared to wild type animals. Results show that Ly6E ablation at hematopoietic stem cells (HSCs) leads to a progressive impaired immune response in both liver and spleen. Specifically, depletion of the normal leukocyte mediated immunity and chemokine signaling is observed in the liver of Ly6E Δ H S C mice. On the other hand, the immune response in the spleen, which seemed to be mediated by an intense chromatin activity in the normal situation, is replaced by ECM remodeling in Ly6E Δ H S C mice. These findings, which require further experimental characterization, could be extrapolated to other coronaviruses and motivate the efforts towards novel antiviral approaches.
Learning an Inclusive Blue Humanities: Oceania and Academia through the Lens of Cinema
Authors: Smith James L. , Mentz Steve
Published: July 2020

Hollywood films such as Pixar’s Moana (2016) and Warner Brothers’ Aquaman (2018) have drawn on the aesthetics and stories of the island cultures of Oceania to inform their narratives. In doing so, these works have both succeeded and failed to respect and engage with oceanic cultural knowledge, providing a cultural vehicle to expand communication, while also exploiting Oceanic culture for financial gain. Cultural tropes and stereotypes pose a heavy intellectual burden that neither film fully shoulders, nor are the complexities of their content acknowledged. Moana sought to enlarge the franchise of the “Disney Princess” genre, but could not avoid issues of cultural appropriation and tokenism becoming entangled with an ongoing process of engagement. Moana’s desire to represent the cultural memory of Oceania raises questions, but while Pixar presents digital fantasy, Aquaman hides its global ambitions beneath star Jason Momoa’s broad shoulders. If the blue humanities is to follow the seminal postcolonial scholarship of Tongan and Fijian cultural theorist Epeli Hau’ofa by exploring a counter-hegemonic narrative in scholarly treatment of the global oceans, then how can it respond with respect? This risk applies equally to academic literary inquiry, with a more inclusive mode of receptive and plural blue humanities as an emerging response.
Do Sports Clubs Contribute to the Accumulation of Regional Social Capital?
Authors: Biernat Elżbieta , Nałęcz Hanna , Skrok Łukasz , Majcherek Dawid
Published: July 2020

Social capital (SC) affects quality of life, sport behaviours and health in individual and community context. The aim was to analyse how sports activity (SA) contributes to SC accumulation in a post-transformation country. A combination of four longitudinal, nationwide datasets was used. Instrumental variable method was applied. Results show that in 19+ Poles, on a regional level, SA improves SC. This suggest that sports clubs and at least some types of sports infrastructure can constitute a valid tool for social policies aiming at improving social involvement. The self-triggering character of SA is a valuable asset for social impact regionally and beyond. It is important to estimate the changes in a long-term perspective, due to the inertness of the SC.
Drought, Climate Change, and Dryland Wheat Yield Response: An Econometric Approach
Authors: Shayanmehr Samira , Rastegari Henneberry Shida , Sabouhi Sabouni Mahmood , Shahnoushi Foroushani Naser
Published: July 2020

Agriculture has been identified as one of the most vulnerable sectors affected by climate change. In the present study, we investigate the impact of climatic change on dryland wheat yield in the northwest of Iran for the future time horizon of 2041–2070. The Just and Pope production function is applied to assess the impact of climate change on dryland wheat yield and yield risk for the period of 1991–2016. The Statistical Downscaling Model (SDSM) is used to generate climate parameters from General Circulation Model (GCM) outputs. The results show that minimum temperature is negatively related to average yield in the linear model while the relationship is positive in the non-linear model. An increase in precipitation increases the mean yield in either model. The maximum temperature has a positive effect on the mean yield in the linear model, while this impact is negative in the non-linear model. Drought has an adverse impact on yield levels in both models. The results also indicate that maximum temperature, precipitation, and drought are positively related to yield variability, but minimum temperature is negatively associated with yield variability. The findings also reveal that yield variability is expected to increase in response to future climate scenarios. Given these impacts of temperature on rain-fed wheat crop and its increasing vulnerability to climatic change, policy-makers should support research into and development of wheat varieties that are resistant to temperature variations.
Mercury Exposure through Fish Consumption in Traditional Communities in the Brazilian Northern Amazon
Authors: Hacon Sandra de Souza , Oliveira-da-Costa Marcelo , Gama Cecile de Souza , Ferreira Renata , Basta Paulo Cesar , Schramm Ana , Yokota Decio
Published: July 2020

Artisanal small-scale gold mining (ASGM) is the main source of anthropogenic mercury emissions and contamination in Latin America. In the Brazilian northern Amazon, ASGM has contaminated the environment and people over the past century. The main contamination route is through fish consumption, which endangers the food security and livelihoods of traditional communities. Our study aims to assess the potential toxicological health risks caused by the consumption of Hg-contaminated fish across five regions in Amapá State. We sampled 428 fish from 18 sites across inland and coastal aquatic systems. We measured the total mercury content in fish samples, and the results were applied to a mercury exposure risk assessment targeting three distinct groups (adults, women of childbearing age, and children). Mercury contamination was found to exceed the World Health Organization’s safe limit in 28.7% of all fish samples, with higher prevalence in inland zones. Moreover, the local preference for carnivorous fish species presents a serious health risk, particularly for communities near inland rivers in the region. This is the first study to provide clear recommendations for reducing the mercury exposure through fish consumption in Amapá State. It builds scientific evidence that helps decision-makers to implement effective policies for protecting the health of riverine communities.
Voluntary Kids’ Meal Beverage Standards: Are They Sufficient to Ensure Healthier Restaurant Practices and Consumer Choices?
Authors: Harpainter Phoebe , Hewawitharana Sridharshi C. , Lee Danielle L. , Martin Anna C. , Gosliner Wendi , Ritchie Lorrene D. , Woodward-Lopez Gail
Published: July 2020

Many quick-service restaurants (QSRs) instituted voluntary kids’ meal default beverage standards (standards) between 2013 to 2017. Little is known about impacts of standards on QSR drive-through practices and on customer choices. This study assessed differences in restaurant practices including kids’ meal beverages shown on menu boards, offered by cashiers, and selected by customers in QSRs with and without voluntary standards. Observations (n = 111) and customer surveys (n = 84) were conducted in 2018 at QSRs with standards (n = 70) and without (n = 41) in low-income California, U.S. neighborhoods. Kids’ meal beverages on menu boards (n = 149) and offered by cashiers (n = 185) at QSRs with and without standards were analyzed using multilevel logistic regression. Significantly more menu boards at QSRs with standards (n = 103) vs. without (n = 46) featured only milk, water or unsweetened juice (65.1% vs. 4.4%; p < 0.001). Most cashiers at QSRs with standards and QSRs without (53.1%, 62.5%) asked what drink the data collector wanted rather than first offering default beverages. A small sample of customer interviews found that customers at QSRs with standards most commonly ordered juice (37.0%); at QSRs without standards, soda (45.5%). Although menu boards showed healthier kids’ meal beverages at QSRs with standards than without, cashier behavior was inconsistent. Results suggest additional measures (legislation, implementation support, enforcement) may be needed to ensure optimal implementation.
Assessing the Governance Context Support for Creating a Pluvial Flood Risk Map with Climate Change Scenarios: The Flemish Subnational Case
Authors: Casiano Flores Cesar , Crompvoets Joep
Published: July 2020

Climate change has increased pluvial flood risks in cities around the world. To mitigate floods, pluvial risk maps with climate change scenarios have been developed to help major urban areas adapt to a changing climate. In some cases, subnational governments have played a key role to develop these maps. However, governance research about the role of subnational governments in geospatial data development in urban water transitions has received little attention. To address this gap, this research applies the Governance Assessment Tool as an evaluative framework to increase our understanding of the governance factors that support the development of pluvial flood risk maps at the subnational level. For this research, we selected the region of Flanders in Belgium. This region is considered among the frontrunners when it comes to the creation of a pluvial flood risk map with climate change scenarios. Data have been collected through in-depth interviews with steering committee actors involved in the development process of the map. The research identified that the current governance context is supportive of the creation of the flood risk map. The government of Flanders plays a key role in this process. The most supportive qualities of the governance context are those related to the degree of fragmentation (extent and coherence), while the less supportive ones are those related to the “quest for control” (flexibility and intensity). Under this governance context, government actors play the primary role. The Flemish government led the maps’ creation process and it was supported by the lower governmental levels. As the provincial government was an important actor to increase local participation, collaboration with private and non-governmental actors in the steering committee was more limited. The financial resources were also limited and the process required a continuous development of trust. Yet, the Flemish Environmental Agency, with the use of technology, was able to increase such trust during the process.
Change Detection in Multispectral Remote Sensing Images with Leader Intelligence PSO and NSCT Feature Fusion
Authors: Paul Josephina , Shankar B. Uma , Bhattacharyya Balaram
Published: July 2020

Change detection (CD) using Remote sensing images have been a challenging problem over the years. Particularly in the unsupervised domain it is even more difficult. A novel automatic change detection technique in the unsupervised framework is proposed to address the real challenges involved in remote sensing change detection. As the accuracy of change map is highly dependent on quality of difference image (DI), a set of Normalized difference images and a complementary set of Normalized Ratio images are fused in the Nonsubsampled Contourlet Transform (NSCT) domain to generate high quality difference images. The NSCT is chosen as it is efficient in suppressing noise by utilizing its unique characteristics such as multidirectionality and shift-invariance that are suitable for change detection. The low frequency sub bands are fused by averaging to combine the complementary information in the two DIs, and, the higher frequency sub bands are merged by minimum energy rule, for preserving the edges and salient features in the image. By employing a novel Particle Swarm Optimization algorithm with Leader Intelligence (LIPSO), change maps are generated from fused sub bands in two different ways: (i) single spectral band, and (ii) combination of spectral bands. In LIPSO, the concept of leader and followers has been modified with intelligent particles performing Lévy flight randomly for better exploration, to achieve global optima. The proposed method achieved an overall accuracy of 99.64%, 98.49% and 97.66% on the three datasets considered, which is very high. The results have been compared with relevant algorithms. The quantitative metrics demonstrate the superiority of the proposed techniques over the other methods and are found to be statistically significant with McNemar’s test. Visual quality of the results also corroborate the superiority of the proposed method.
Exploring the Spatial Distribution Characteristics of Emotions of Weibo Users in Wuhan Waterfront Based on Gender Differences Using Social Media Texts
Authors: Ma Yue , Ling Changlong , Wu Jing
Published: July 2020

The benefits of the natural environment in urban space have been explored in numerous studies. However, only a few statistics and studies have been conducted on the correlation between emotion and urban waterfront space, especially considering gender differences. Taking Wuhan city as an example, this study puts forward a new approach and perspective. Text emotion analysis is combined with the spatial analysis technique based on big data of social media. Based on the emotions of the public of different genders in urban space, suggestions are provided for urban planning and development from the perspective of POI (Point of Interest). The main steps are: (1) Analyzing the emotional score of Weibo texts published by citizens in the waterfront area of 21 lakes in Wuhan City; (2) exploring the public emotion characteristics of different genders in the urban waterfront; (3) classifying the waterfront according to the emotional response (score) of the public of different genders; (4) exploring the relationship between different POI types and waterfront types and proposing planning suggestions. The results of this study provide evidence for gender differences and spatial distribution of public emotions in the Wuhan waterfront area. It can help decision-makers to judge the prior protection and development direction of waterfront space, thus demonstrating the feasibility of this approach.
Red and Yellow Injectable Platelet-Rich Fibrin Demonstrated Differential Effects on Periodontal Ligament Stem Cell Proliferation, Migration, and Osteogenic Differentiation
Authors: Thanasrisuebwong Prakan , Kiattavorncharoen Sirichai , Surarit Rudee , Phruksaniyom Chareerut , Ruangsawasdi Nisarat
Published: July 2020

The biological benefits of using two fractions derived from injectable platelet-rich fibrin (i-PRF) in bone regeneration remain unclear. Thus, the current study examined two fractionation protocols producing yellow i-PRF and red i-PRF on periodontal ligament stem cells (PDLSCs). The i-PRF samples from five donors were harvested from two different levels, with and without a buffy coat layer, to obtain red and yellow i-PRF, respectively. The PDLSCs were isolated and characterized before their experimental use. The culture medium in each assay was loaded with 20% of the conditioned medium containing the factors released from the red and yellow i-PRF. Cell proliferation and cell migration were determined with an MTT and trans-well assay, respectively. Osteogenic differentiation was investigated using alkaline phosphatase and Alizarin red staining. The efficiency of both i-PRFs was statistically compared. We found that the factors released from the red i-PRF had a greater effect on cell proliferation and cell migration. Moreover, the factors released from the yellow i-PRF stimulated PDLSC osteogenic differentiation earlier compared with the red i-PRF. These data suggest that the red i-PRF might be suitable for using in bone regeneration because it induced the mobilization and growth of bone regenerative cells without inducing premature mineralization.
The Application of Molecular Spectroscopy in Combination with Chemometrics for Halal Authentication Analysis: A Review
Authors: Rohman Abdul , Windarsih Anjar
Published: July 2020

Halal is an Arabic term used to describe any components allowed to be used in any products by Muslim communities. Halal food and halal pharmaceuticals are any food and pharmaceuticals which are safe and allowed to be consumed according to Islamic law (Shariah). Currently, in line with halal awareness, some Muslim countries such as Indonesia, Malaysia, and Middle East regions have developed some standards and regulations on halal products and halal certification. Among non-halal components, the presence of pig derivatives (lard, pork, and porcine gelatin) along with other non-halal meats (rat meat, wild boar meat, and dog meat) is typically found in food and pharmaceutical products. This review updates the recent application of molecular spectroscopy, including ultraviolet-visible, infrared, Raman, and nuclear magnetic resonance (NMR) spectroscopies, in combination with chemometrics of multivariate analysis, for analysis of non-halal components in food and pharmaceutical products. The combination of molecular spectroscopic-based techniques and chemometrics offers fast and reliable methods for screening the presence of non-halal components of pig derivatives and non-halal meats in food and pharmaceutical products.
EPAC in Vascular Smooth Muscle Cells
Authors: Wehbe Nadine , Nasser Suzanne Awni , Al-Dhaheri Yusra , Iratni Rabah , Bitto Alessandra , El-Yazbi Ahmed F. , Badran Adnan , Kobeissy Firas , Baydoun Elias , Eid Ali H.
Published: July 2020

Vascular smooth muscle cells (VSMCs) are major components of blood vessels. They regulate physiological functions, such as vascular tone and blood flow. Under pathological conditions, VSMCs undergo a remodeling process known as phenotypic switching. During this process, VSMCs lose their contractility and acquire a synthetic phenotype, where they over-proliferate and migrate from the tunica media to the tunica interna, contributing to the occlusion of blood vessels. Since their discovery as effector proteins of cyclic adenosine 3′,5′-monophosphate (cAMP), exchange proteins activated by cAMP (EPACs) have been shown to play vital roles in a plethora of pathways in different cell systems. While extensive research to identify the role of EPAC in the vasculature has been conducted, much remains to be explored to resolve the reported discordance in EPAC’s effects. In this paper, we review the role of EPAC in VSMCs, namely its regulation of the vascular tone and phenotypic switching, with the likely involvement of reactive oxygen species (ROS) in the interplay between EPAC and its targets/effectors.
Identification of Subclinical Lung Involvement in ACPA-Positive Subjects through Functional Assessment and Serum Biomarkers
Authors: Lucchino Bruno , Di Paolo Marcello , Gioia Chiara , Vomero Marta , Diacinti Davide , Mollica Cristina , Alessandri Cristiano , Diacinti Daniele , Palange Paolo , Di Franco Manuela
Published: July 2020

Lung involvement is related to the natural history of anti-citrullinated proteins antibodies (ACPA)-positive rheumatoid arthritis (RA), both during the pathogenesis of the disease and as a site of disease-related injury. Increasing evidence suggests that there is a subclinical, early lung involvement during the course of the disease, even before the onset of articular manifestations, which can potentially progress to a symptomatic interstitial lung disease. To date, reliable, non-invasive markers of subclinical lung involvement are still lacking in clinical practice. The aim of this study is to evaluate the diagnostic potential of functional assessment and serum biomarkers in the identification of subclinical lung involvement in ACPA-positive subjects. Fifty ACPA-positive subjects with or without confirmed diagnosis of RA (2010 ARC-EULAR criteria) were consecutively enrolled. Each subject underwent clinical evaluation, pulmonary function testing (PFT) with assessment of diffusion lung capacity for carbon monoxide (DLCO), cardiopulmonary exercise testing (CPET), surfactant protein D (SPD) serum levels dosage and high-resolution computed tomography (HRCT) of the chest. The cohort was composed of 21 ACPA-positive subjects without arthritis (ND), 10 early (disease duration < 6 months, treatment-naïve) RA (ERA) and 17 long-standing (disease duration < 36 months, on treatment) RA (LSRA). LSRA patients had a significantly higher frequency of overall HRCT abnormalities compared to the other groups (p = 0.001). SPD serum levels were significantly higher in ACPA-positive subjects compared with healthy controls (158.5 ± 132.3 ng/mL vs 61.27 ± 34.11 ng/mL; p < 0.0001) and showed an increasing trend from ND subjects to LSRD patients (p = 0.004). Patients with HRCT abnormalities showed significantly lower values of DLCO (74.19 ± 13.2% pred. vs 131.7 ± 93% pred.; p = 0.009), evidence of ventilatory inefficiency at CPET and significantly higher SPD serum levels compared with subjects with no HRCT abnormalities (213.5 ± 157.2 ng/mL vs 117.7 ± 157.3 ng/mL; p = 0.018). Abnormal CPET responses and higher SPD levels were also associated with specific radiological findings. Impaired DLCO and increased SPD serum levels were independently associated with the presence of HRCT abnormalities. Subclinical lung abnormalities occur early in RA-associated autoimmunity. The presence of subclinical HRCT abnormalities is associated with several functional abnormalities and increased SPD serum levels of SPD. Functional evaluation through PFT and CPET, together with SPD assessment, may have a diagnostic potential in ACPA-positive subjects, contributing to the identification of those patients to be referred to HRCT scan.
Covid-19: The Rollercoaster of Fibrin(Ogen), D-Dimer, Von Willebrand Factor, P-Selectin and Their Interactions with Endothelial Cells, Platelets and Erythrocytes
Authors: Grobler Corlia , Maphumulo Siphosethu C. , Grobbelaar L. Mireille , Bredenkamp Jhade C. , Laubscher Gert J. , Lourens Petrus J. , Steenkamp Janami , Kell Douglas B. , Pretorius Etheresia
Published: July 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), also known as coronavirus disease 2019 (COVID-19)-induced infection, is strongly associated with various coagulopathies that may result in either bleeding and thrombocytopenia or hypercoagulation and thrombosis. Thrombotic and bleeding or thrombotic pathologies are significant accompaniments to acute respiratory syndrome and lung complications in COVID-19. Thrombotic events and bleeding often occur in subjects with weak constitutions, multiple risk factors and comorbidities. Of particular interest are the various circulating inflammatory coagulation biomarkers involved directly in clotting, with specific focus on fibrin(ogen), D-dimer, P-selectin and von Willebrand Factor (VWF). Central to the activity of these biomarkers are their receptors and signalling pathways on endothelial cells, platelets and erythrocytes. In this review, we discuss vascular implications of COVID-19 and relate this to circulating biomarker, endothelial, erythrocyte and platelet dysfunction. During the progression of the disease, these markers may either be within healthy levels, upregulated or eventually depleted. Most significant is that patients need to be treated early in the disease progression, when high levels of VWF, P-selectin and fibrinogen are present, with normal or slightly increased levels of D-dimer (however, D-dimer levels will rapidly increase as the disease progresses). Progression to VWF and fibrinogen depletion with high D-dimer levels and even higher P-selectin levels, followed by the cytokine storm, will be indicative of a poor prognosis. We conclude by looking at point-of-care devices and methodologies in COVID-19 management and suggest that a personalized medicine approach should be considered in the treatment of patients.
Osteocyte-Related Cytokines Regulate Osteoclast Formation and Bone Resorption
Authors: Kitaura Hideki , Marahleh Aseel , Ohori Fumitoshi , Noguchi Takahiro , Shen Wei-Ren , Qi Jiawei , Nara Yasuhiko , Pramusita Adya , Kinjo Ria , Mizoguchi Itaru
Published: July 2020

The process of bone remodeling is the result of the regulated balance between bone cell populations, namely bone-forming osteoblasts, bone-resorbing osteoclasts, and the osteocyte, the mechanosensory cell type. Osteoclasts derived from the hematopoietic stem cell lineage are the principal cells involved in bone resorption. In osteolytic diseases such as rheumatoid arthritis, periodontitis, and osteoporosis, the balance is lost and changes in favor of bone resorption. Therefore, it is vital to elucidate the mechanisms of osteoclast formation and bone resorption. It has been reported that osteocytes express Receptor activator of nuclear factor κΒ ligand (RANKL), an essential factor for osteoclast formation. RANKL secreted by osteocytes is the most important factor for physiologically supported osteoclast formation in the developing skeleton and in pathological bone resorption such as experimental periodontal bone loss. TNF-α directly enhances RANKL expression in osteocytes and promotes osteoclast formation. Moreover, TNF-α enhances sclerostin expression in osteocytes, which also increases osteoclast formation. These findings suggest that osteocyte-related cytokines act directly to enhance osteoclast formation and bone resorption. In this review, we outline the most recent knowledge concerning bone resorption-related cytokines and discuss the osteocyte as the master regulator of bone resorption and effector in osteoclast formation.
Protective Effect of Epigallocatechin-3-Gallate (EGCG) in Diseases with Uncontrolled Immune Activation: Could Such a Scenario Be Helpful to Counteract COVID-19?
Authors: Menegazzi Marta , Campagnari Rachele , Bertoldi Mariarita , Crupi Rosalia , Di Paola Rosanna , Cuzzocrea Salvatore
Published: July 2020

Some coronavirus disease 2019 (COVID-19) patients develop acute pneumonia which can result in a cytokine storm syndrome in response to Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection. The most effective anti-inflammatory drugs employed so far in severe COVID-19 belong to the cytokine-directed biological agents, widely used in the management of many autoimmune diseases. In this paper we analyze the efficacy of epigallocatechin 3-gallate (EGCG), the most abundant ingredient in green tea leaves and a well-known antioxidant, in counteracting autoimmune diseases, which are dominated by a massive cytokines production. Indeed, many studies registered that EGCG inhibits signal transducer and activator of transcription (STAT)1/3 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) transcription factors, whose activities are crucial in a multiplicity of downstream pro-inflammatory signaling pathways. Importantly, the safety of EGCG/green tea extract supplementation is well documented in many clinical trials, as discussed in this review. Since EGCG can restore the natural immunological homeostasis in many different autoimmune diseases, we propose here a supplementation therapy with EGCG in COVID-19 patients. Besides some antiviral and anti-sepsis actions, the major EGCG benefits lie in its anti-fibrotic effect and in the ability to simultaneously downregulate expression and signaling of many inflammatory mediators. In conclusion, EGCG can be considered a potential safe natural supplement to counteract hyper-inflammation growing in COVID-19.
Early Life Oxidative Stress and Long-Lasting Cardiovascular Effects on Offspring Conceived by Assisted Reproductive Technologies: A Review
Authors: Yang Huixia , Kuhn Christina , Kolben Thomas , Ma Zhi , Lin Peng , Mahner Sven , Jeschke Udo , von Schönfeldt Viktoria
Published: July 2020

Assisted reproductive technology (ART) has rapidly developed and is now widely practised worldwide. Both the characteristics of ART (handling gametes/embryos in vitro) and the infertility backgrounds of ART parents (such as infertility diseases and unfavourable lifestyles or diets) could cause increased oxidative stress (OS) that may exert adverse influences on gametogenesis, fertilisation, and foetation, even causing a long-lasting influence on the offspring. For these reasons, the safety of ART needs to be closely examined. In this review, from an ART safety standpoint, the origins of OS are reviewed, and the long-lasting cardiovascular effects and potential mechanisms of OS on the offspring are discussed.
Heterogeneous Polymer Dynamics Explored Using Static 1H NMR Spectra
Authors: Alam Todd M. , Allers Joshua P. , Jones Brad H.
Published: July 2020

NMR spectroscopy continues to provide important molecular level details of dynamics in different polymer materials, ranging from rubbers to highly crosslinked composites. It has been argued that thermoset polymers containing dynamic and chemical heterogeneities can be fully cured at temperatures well below the final glass transition temperature (Tg). In this paper, we described the use of static solid-state 1H NMR spectroscopy to measure the activation of different chain dynamics as a function of temperature. Near Tg, increasing polymer segmental chain fluctuations lead to dynamic averaging of the local homonuclear proton-proton (1H-1H) dipolar couplings, as reflected in the reduction of the NMR line shape second moment (M2) when motions are faster than the magnitude of the dipolar coupling. In general, for polymer systems, distributions in the dynamic correlation times are commonly expected. To help identify the limitations and pitfalls of M2 analyses, the impact of activation energy or, equivalently, correlation time distributions, on the analysis of 1H NMR M2 temperature variations is explored. It is shown by using normalized reference curves that the distributions in dynamic activation energies can be measured from the M2 temperature behavior. An example of the M2 analysis for a series of thermosetting polymers with systematically varied dynamic heterogeneity is presented and discussed.
Biological Properties, Bioactive Constituents, and Pharmacokinetics of Some Capsicum spp. and Capsaicinoids
Authors: Batiha Gaber El-Saber , Alqahtani Ali , Ojo Oluwafemi Adeleke , Shaheen Hazem M. , Wasef Lamiaa , Elzeiny Mahmoud , Ismail Mahmoud , Shalaby Mahmoud , Murata Toshihiro , Zaragoza-Bastida Adrian , Rivero-Perez Nallely , Magdy Beshbishy Amany , Kasozi Keneth Iceland , Jeandet Philippe , Hetta Helal F.
Published: July 2020

Pepper originated from the Capsicum genus, which is recognized as one of the most predominant and globally distributed genera of the Solanaceae family. It is a diverse genus, consisting of more than 31 different species including five domesticated species, Capsicum baccatum, C. annuum, C. pubescen, C. frutescens, and C. chinense. Pepper is the most widely used spice in the world and is highly valued due to its pungency and unique flavor. Pepper is a good source of provitamin A; vitamins E and C; carotenoids; and phenolic compounds such as capsaicinoids, luteolin, and quercetin. All of these compounds are associated with their antioxidant as well as other biological activities. Interestingly, Capsicum fruits have been used as food additives in the treatment of toothache, parasitic infections, coughs, wound healing, sore throat, and rheumatism. Moreover, it possesses antimicrobial, antiseptic, anticancer, counterirritant, appetite stimulator, antioxidant, and immunomodulator activities. Capsaicin and Capsicum creams are accessible in numerous ways and have been utilized in HIV-linked neuropathy and intractable pain.
Assessing Molecular Docking Tools to Guide Targeted Drug Discovery of CD38 Inhibitors
Authors: Boittier Eric D. , Tang Yat Yin , Buckley McKenna E. , Schuurs Zachariah P. , Richard Derek J. , Gandhi Neha S.
Published: July 2020

A promising protein target for computational drug development, the human cluster of differentiation 38 (CD38), plays a crucial role in many physiological and pathological processes, primarily through the upstream regulation of factors that control cytoplasmic Ca2+ concentrations. Recently, a small-molecule inhibitor of CD38 was shown to slow down pathways relating to aging and DNA damage. We examined the performance of seven docking programs for their ability to model protein-ligand interactions with CD38. A test set of twelve CD38 crystal structures, containing crystallized biologically relevant substrates, were used to assess pose prediction. The rankings for each program based on the median RMSD between the native and predicted were Vina, AD4 > PLANTS, Gold, Glide, Molegro > rDock. Forty-two compounds with known affinities were docked to assess the accuracy of the programs at affinity/ranking predictions. The rankings based on scoring power were: Vina, PLANTS > Glide, Gold > Molegro >> AutoDock 4 >> rDock. Out of the top four performing programs, Glide had the only scoring function that did not appear to show bias towards overpredicting the affinity of the ligand-based on its size. Factors that affect the reliability of pose prediction and scoring are discussed. General limitations and known biases of scoring functions are examined, aided in part by using molecular fingerprints and Random Forest classifiers. This machine learning approach may be used to systematically diagnose molecular features that are correlated with poor scoring accuracy.
Long-Term Outcomes of Patients with Unprotected Left Main Coronary Artery Disease Treated with Percutaneous Angioplasty versus Bypass Grafting: A Meta-Analysis of Randomized Controlled Trials
Authors: Bajraktari Gani , Zhubi-Bakija Fjolla , Ndrepepa Gjin , Alfonso Fernando , Elezi Shpend , Rexhaj Zarife , Bytyçi Ibadete , Bajraktari Artan , Poniku Afrim , Henein Michael Y.
Published: July 2020

Background and Aim: Treatment of patients with left main coronary artery disease (LMCA) with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) remains controversial. The aim of this meta-analysis was to compare the long-term clinical outcomes of patients with unprotected LMCA treated randomly by PCI or CABG. Methods: PubMed, MEDLINE, Embase, Scopus, Google Scholar, CENTRAL and ClinicalTrials.gov database searches identified five randomized trials (RCTs) including 4499 patients with unprotected LMCA comparing PCI (n = 2249) vs. CABG (n = 2250), with a minimum clinical follow-up of five years. Random effect risk ratios were used for efficacy and safety outcomes. The study was registered in PROSPERO. The primary outcome was major adverse cardiac events (MACE), defined as a composite of death from any cause, myocardial infarction or stroke. Results: Compared to CABG, patients assigned to PCI had a similar rate of MACE (risk ratio (RR): 1.13; 95% CI: 0.94 to 1.36; p = 0.19), myocardial infarction (RR: 1.48; 95% CI: 0.97 to 2.25; p = 0.07) and stroke (RR: 0.87; 95% CI: 0.62 to 1.23; p = 0.42). Additionally, all-cause mortality (RR: 1.07; 95% CI: 0.89 to 1.28; p = 0.48) and cardiovascular (CV) mortality (RR: 1.13; 95% CI: 0.89 to 1.43; p = 0.31) were not different. However, the risk of any repeat revascularization (RR: 1.70; 95% CI: 1.34 to 2.15; p < 0.00001) was higher in patients assigned to PCI. Conclusions: The findings of this meta-analysis suggest that the long-term survival and MACE of patients who underwent PCI for unprotected LMCA stenosis were comparable to those receiving CABG, despite a higher rate of repeat revascularization.
Blockade of Platelet-Derived Growth Factor Signaling Inhibits Choroidal Neovascularization and Subretinal Fibrosis in Mice
Authors: Liu Ye , Noda Kousuke , Murata Miyuki , Wu Di , Kanda Atsuhiro , Ishida Susumu
Published: July 2020

Neovascular age related macular degeneration (nAMD) leads to severe vision loss worldwide and is characterized by the formation of choroidal neovascularization (CNV) and fibrosis. In the current study, we aimed to investigate the effect of blockade for platelet derived growth factor receptor-β (PDGFR-β) on the formation of choroidal neovascularization and fibrosis in the laser-induced CNV model in mice. Firstly, the presence of PDGFR-β in CNV lesions were confirmed. Intravitreal injection of PDGFR-β neutralizing antibody significantly reduced the size of CNV and subretinal fibrosis. Additionally, subretinal hyperreflective material (SHRM), a landmark feature on OCT as a risk factor for subretinal fibrosis formation in nAMD patients was also suppressed by PDGFR-β blockade. Furthermore, pericytes were abundantly recruited to the CNV lesions during CNV formation, however, blockade of PDGFR-β significantly reduced pericyte recruitment. In addition, PDGF-BB stimulation increased the migration of the rat retinal pericyte cell line, R-rPCT1, which was abrogated by the neutralization of PDGFR-β. These results indicate that blockade of PDGFR-β attenuates laser-induced CNV and fibrosis through the inhibition of pericyte migration.
Effects of Evolocumab on Carotid Intima-Media Thickness and Clinical Parameters in Patients Taking a Statin
Authors: Hirai Keiji , Imamura Shigeki , Hirai Aizan , Ookawara Susumu , Morishita Yoshiyuki
Published: July 2020

We determined the effects of evolocumab, a fully human monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9, on carotid intima-media thickness (IMT) and the factors associated with the change in carotid IMT in patients taking a statin. The change in carotid mean and maximum IMT before and after the initiation of evolocumab treatment was retrospectively analyzed in 229 statin-treated patients. The changes in clinical parameters, including serum lipid concentrations, were also evaluated. Evolocumab significantly reduced the increase in carotid mean and maximum IMT (0.09 ± 0.13 mm/year to −0.04 ± 0.16 mm/year, p < 0.001 and 0.17 ± 0.38 mm/year to 0.08 ± 0.47 mm/year, p = 0.02). Evolocumab reduced serum total cholesterol, low-density lipoprotein-cholesterol, triglyceride, and lipoprotein (a) concentrations (each p < 0.001), and increased serum high-density lipoprotein (HDL)-cholesterol concentrations (p = 0.01). Multiple linear regression analysis revealed that the change in HDL-cholesterol (standard coefficient (β) = −0.120, p = 0.04) and carotid mean IMT (β = −0.467, p < 0.001) were independently correlated with the change in carotid mean IMT during the administration of evolocumab, whereas the change in HDL-cholesterol (β = −0.208, p = 0.002) and log-triglyceride (β = −0.167, p = 0.01) independently correlated with the change in carotid maximum IMT. Evolocumab reduced the increase in carotid IMT in patients taking a statin. These results suggest that evolocumab is protective against carotid atherosclerosis in patients undergoing statin therapy.
A Randomized Controlled Trial of Thermo-Sensitive Sol–Gel Anti-Adhesion Agent after Gynecologic Surgery
Authors: Kim Young Im , Lee Maria , Kim Se Ik , Seol Aeran , Lee Eun Ji , Kim Hee Seung , Song Yong Sang
Published: July 2020

Postoperative abdominal adhesions can lead to several adverse consequences such as pelvic pain, bowel obstruction, and infertility. We aimed to explore the anti-adhesion efficacy and safety of a thermo-sensitive sol–gel agent in patients who receive abdominopelvic surgery for benign gynecologic disease. This study was a randomized, controlled, single-blind clinical trial of women undergoing benign gynecologic surgery between January 2017 and December 2017. The patients were randomly assigned to three groups with a 1:1:1 ratio: experimental group (received the thermo-sensitive sol–gel agent), control group (untreated), and comparator group (received 4% icodextrin). Patients were followed for 4 weeks postoperatively, and efficacy was evaluated by performing the visceral slide test to identify adhesion formation. In total, 183 patients were enrolled in the study, and 178 (97.3%) completed the trial. The incidence rate of abdominal adhesion formation was significantly lower in the experimental group than in the control group (7.9% vs. 21.1%, p = 0.040); however, it was similar between the experimental and comparator groups (7.9% vs. 13.8%. p = 0.299). At 4 weeks, no differences in adhesion-related symptoms were observed between the experimental and control groups. Adverse events were mostly mild and did not differ significantly among the three groups (p = 0.375). In conclusion, use of a thermo-sensitive sol–gel agent was safe and effective to prevent abdominal adhesions after benign gynecologic surgeries.
Changes in High-Density Lipoproteins Related to Outcomes in Patients with Acute Stroke
Authors: Varela Lourdes M. , Meseguer Elena , Lapergue Bertrand , Couret David , Amarenco Pierre , Meilhac Olivier
Published: July 2020

Modifications in high-density lipoprotein (HDL) particle sizes and HDL-binding proteins have been reported in stroke patients. We evaluated whether the lipoprotein profile, HDL composition and functionality were altered in stroke patients according to their clinical outcome using the modified Rankin Score at 3 months. Plasma samples were obtained from stroke patients treated with intravenous thrombolysis. Levels of cardiovascular and inflammatory markers in plasma were measured using the Human CVD Panel 1 (Milliplex® MAP). Lipoprotein subfractions from plasma were quantified by non-denaturing acrylamide gel electrophoresis, using the Lipoprint®-System (Quantimetrix®), and HDLs were isolated by ultracentrifugation. Relative amounts of paraoxonase-1 (PON1) and alpha-1 anti-trypsin (AAT) in the isolated HDLs were determined by Western blot. HDL anti-inflammatory function was evaluated in human blood–brain barrier endothelial cells stimulated with 100 ng/mL TNFα, and HDL antioxidant function was evaluated via their capacity to limit copper-induced low-density lipoprotein oxidation. Stroke patients with unfavorable outcomes had a lower proportion of small-sized HDLs and increased plasma levels of E-selectin (SELE) and the intercellular adhesion molecule 1 (ICAM1). HDLs from patients with unfavorable outcomes had lower levels of PON1 and displayed a blunted capacity to reduce the expression of SELE, interleukin 8 (IL8) and the monocyte chemoattractant protein-1 (MCP1) mRNA induced by TNFα in endothelial cells. These HDLs also had a reduced antioxidant capacity relative to HDLs from healthy donors. In conclusion, an increased ratio of large/small HDLs with impaired anti-inflammatory and antioxidant capacities was associated with unfavorable outcomes in stroke patients. Alteration of HDL functionality was mainly associated with a low amount of PON1 and high amount of AAT.
Nivolumab for Previously Treated Patients with Non-Small-Cell Lung Cancer—Daily Practice versus Clinical Trials
Authors: Knetki-Wróblewska Magdalena , Kowalski Dariusz M. , Krzakowski Maciej
Published: July 2020

Based on the results of the CheckMate 017 and CheckMate 057 studies, nivolumab therapy has become a new standard treatment for both squamous and non-squamous non-small-cell lung cancer (NSCLC). However, due to the specific inclusion criteria of these clinical trials, the efficacy and safety of nivolumab in real-world practice were not certain. In general, the real-world results of nivolumab treatment have been consistent with those obtained in clinical trials. Additional analyses of the real-world data have made the identification of prognostic factors possible. Good performance status is the most significant predictor of clinical benefit. Brain metastases, liver metastases, EGFR mutation, malignant pleural effusion, and a high number of metastatic sites were identified as negative prognostic factors. By contrast, a longer time to disease progression (>6 months) from the beginning of prior chemotherapy and an objective response to chemotherapy seem to have positive prognostic value in the case of nivolumab treatment. In terms of patient age, the data are inconclusive. Some blood biomarkers can also be considered significant prognostic factors.
Prolonged Length of Stay in the Emergency Department and Increased Risk of In-Hospital Cardiac Arrest: A nationwide Population-Based Study in South Korea, 2016–2017
Authors: Kim June-sung , Seo Dong Woo , Kim Youn-Jung , Jeong Jinwoo , Kang Hyunggoo , Han Kap Su , Kim Su Jin , Lee Sung Woo , Ahn Shin , Kim Won Young
Published: July 2020

This study was to determine whether prolonged emergency department (ED) length of stay (LOS) is associated with increased risk of in-hospital cardiac arrest (IHCA). A retrospective cohort with a nationwide database of all adult patients who visited the EDs in South Korea between January 2016 and December 2017 was performed. A total of 18,217,034 patients visited an ED during the study period. The median ED LOS was 2.5 h. IHCA occurred in 9,180 patients (0.2%). IHCA was associated with longer ED LOS (4.2 vs. 2.5 h), and higher rates of intensive care unit (ICU) admission (58.6% vs. 4.7%) and in-hospital mortality (35.7% vs. 1.5%). The ED LOS correlated positively with the development of IHCA (Spearman ρ = 0.91; p < 0.01) and was an independent risk factor for IHCA (odds ratio (OR) 1.10; 95% confidence interval (CI), 1.10–1.10). The development of IHCA increased in a stepwise fashion across increasing quartiles of ED LOS, with ORs for the second, third, and fourth relative to the first being 3.35 (95% CI, 3.26–3.44), 3.974 (95% CI, 3.89–4.06), and 4.97 (95% CI, 4.89–5.05), respectively. ED LOS should be reduced to prevent adverse events in patients visiting the ED.
Neuroendocrine Modulation of the Immune Response after Trauma and Sepsis: Does It Influence Outcome?
Authors: Kobbe Philipp , Bläsius Felix M. , Lichte Philipp , Oberbeck Reiner , Hildebrand Frank
Published: July 2020

Although the treatment of multiple-injured patients has been improved during the last decades, sepsis and multiple organ failure (MOF) still remain the major cause of death. Following trauma, profound alterations of a large number of physiological systems can be observed that may potentially contribute to the development of sepsis and MOF. This includes alterations of the neuroendocrine and the immune system. A large number of studies focused on posttraumatic changes of the immune system, but the cause of posttraumatic immune disturbance remains to be established. However, an increasing number of data indicate that the bidirectional interaction between the neuroendocrine and the immune system may be an important mechanism involved in the development of sepsis and MOF. The aim of this article is to highlight the current knowledge of the neuroendocrine modulation of the immune system during trauma and sepsis.