bluuebunny/crossref_metadata_2025 huggingface dataset:
Hybrid Nanofluids as Renewable and Sustainable Colloidal Suspensions for Potential Photovoltaic/Thermal and Solar Energy Applications
Authors: Rasheed Tahir , Hussain Tariq , Anwar Muhammad Tuoqeer , Ali Jazib , Rizwan Komal , Bilal Muhammad , Alshammari Fwzah H. , Alwadai Norah , Almuslem Amani Saleh
Published: September 2021

The comparative utilization of solar thermal or photovoltaic systems has significantly increased to fulfill the requirement of electricity and heat since few decades. These hybrid systems produce both thermal and electrical energy simultaneously. In recent times, increasing interest is being redirected by researchers in exploiting variety of nanoparticles mixed with miscellaneous base fluids (hybrid nanofluid) for these hybrid systems. This new class of colloidal suspensions has many fascinating advantages as compared to conventional types of nanofluids because of their modified and superior rheological and thermophysical properties which makes them appealing for solar energy devices. Here, we have attempted to deliver an extensive overview of the synthetic methodologies of hybrid nanofluids and their potential in PV/T and solar thermal energy systems. A detailed comparison between conventional types of nanofluids and hybrid nanofluids has been carried out to present in-depth understanding of the advantages of the hybrid nanofluids. The documented reports reveal that enhanced thermal properties of hybrid nanofluids promise the increased performance of solar thermal PV/T systems. Additionally, the unique properties such as nanoparticles concentration and type of base fluid, etc. greatly influence the behavior of hybrid nanofluidic systems. Finally, the outlook, suggestions, and challenges for future research directions are discussed.
European Carbon Dioxide Removal Policy: Current Status and Future Opportunities
Authors: Tamme Eve , Beck Larissa Lee
Published: September 2021

Over the past two years, the European Union, Norway, Iceland, and the UK have increased climate ambition and aggressively pushed forward an agenda to pursue climate neutrality or net-zero emissions by mid-century. This increased ambition, partly the result of the Intergovernmental Panel on Climate Change's landmark findings on limiting global warming to 1.5°C, has also led to a renewed approach to and revitalized debate about the role of carbon capture and storage and carbon dioxide removal. With increasing climate ambition, including a mid-century climate neutrality goal for the whole European Union, the potential role of technological carbon dioxide removal (CDR) is emerging as one of the critical points of debate among NGOs, policymakers, and the private sector. Policymakers are starting to discuss how to incentivize a CDR scale-up. What encompasses the current debate, and how does it relate to CDR technologies' expected role in reaching climate neutrality? This perspective will highlight that policy must fill two gaps: the accounting and the commercialization gap for the near-term development of a comprehensive CDR policy framework. It will shine a light on the current status of negative emission technologies and the role of carbon capture and storage in delivering negative emissions in Europe's decarbonized future. It will also analyze the role of carbon markets, including voluntary markets, as potential incentives while exploring policy pathways for a near-term scale-up.
NPARS—A Novel Approach to Address Accuracy and Reproducibility in Genomic Data Science
Authors: Ma Li , Peterson Erich A. , Shin Ik Jae , Muesse Jason , Marino Katy , Steliga Matthew A. , Johann Donald J.
Published: September 2021

Background: Accuracy and reproducibility are vital in science and presents a significant challenge in the emerging discipline of data science, especially when the data are scientifically complex and massive in size. Further complicating matters, in the field of genomic-based science high-throughput sequencing technologies generate considerable amounts of data that needs to be stored, manipulated, and analyzed using a plethora of software tools. Researchers are rarely able to reproduce published genomic studies.

Results: Presented is a novel approach which facilitates accuracy and reproducibility for large genomic research data sets. All data needed is loaded into a portable local database, which serves as an interface for well-known software frameworks. These include python-based Jupyter Notebooks and the use of RStudio projects and R markdown. All software is encapsulated using Docker containers and managed by Git, simplifying software configuration management.

Conclusion: Accuracy and reproducibility in science is of a paramount importance. For the biomedical sciences, advances in high throughput technologies, molecular biology and quantitative methods are providing unprecedented insights into disease mechanisms. With these insights come the associated challenge of scientific data that is complex and massive in size. This makes collaboration, verification, validation, and reproducibility of findings difficult. To address these challenges the NGS post-pipeline accuracy and reproducibility system (NPARS) was developed. NPARS is a robust software infrastructure and methodology that can encapsulate data, code, and reporting for large genomic studies. This paper demonstrates the successful use of NPARS on large and complex genomic data sets across different computational platforms.
Post-Translational Modifications of FXR; Implications for Cholestasis and Obesity-Related Disorders
Authors: Appelman Monique D. , van der Veen Suzanne W. , van Mil Saskia W. C.
Published: September 2021

The Farnesoid X receptor (FXR) is a nuclear receptor which is activated by bile acids. Bile acids function in solubilization of dietary fats and vitamins in the intestine. In addition, bile acids have been increasingly recognized to act as signaling molecules involved in energy metabolism pathways, amongst others via activating FXR. Upon activation by bile acids, FXR controls the expression of many genes involved in bile acid, lipid, glucose and amino acid metabolism. An inability to properly use and store energy substrates may predispose to metabolic disorders, such as obesity, diabetes, cholestasis and non-alcoholic fatty liver disease. These diseases arise through a complex interplay between genetics, environment and nutrition. Due to its function in metabolism, FXR is an attractive treatment target for these disorders. The regulation of FXR expression and activity occurs both at the transcriptional and at the post-transcriptional level. It has been shown that FXR can be phosphorylated, SUMOylated and acetylated, amongst other modifications, and that these modifications have functional consequences for DNA and ligand binding, heterodimerization and subcellular localization of FXR. In addition, these post-translational modifications may selectively increase or decrease transcription of certain target genes. In this review, we provide an overview of the posttranslational modifications of FXR and discuss their potential involvement in cholestatic and metabolic disorders.
Palm Functional Traits, Soil Fertility and Hydrology Relationships in Western Amazonia
Authors: Trujillo William , Rivera-Rondón Carlos A. , Balslev Henrik
Published: September 2021

Quantification of multivariate trait spectra (or axes of specialization) make the definition of plant strategies more operational, which promotes trait-based theory of community assembly and the understanding of dynamics and functioning of ecosystems. We used field-quantified soil data to explore trait-environment relationships across palm communities in western Amazonia. We collected data from 116 palm species in 458 transects across four distinct forest types. We combined these data with trait records to relate local plant community trait composition to broad gradients in soil variables and forest types. There were significant trait-environment relationships across western Amazonia. Palms with large leaves and fruits, and palms with both growth forms (acaulescent/erect) were associated with fertile soils, while palms with unarmed leaves and stems were associated with non-inundated environments. These results suggest that the functional traits of palms vary consistently along soil gradients on a regional scale. This variation could be explained by the soil fertility and acidity + aluminum gradients, suggesting environmental filters related to resource availability and stressful environments, such as acid soils and soils with high aluminum content.
Myogenic Cell Transplantation in Genetic and Acquired Diseases of Skeletal Muscle
Authors: Boyer Olivier , Butler-Browne Gillian , Chinoy Hector , Cossu Giulio , Galli Francesco , Lilleker James B. , Magli Alessandro , Mouly Vincent , Perlingeiro Rita C. R. , Previtali Stefano C. , Sampaolesi Maurilio , Smeets Hubert , Schoewel-Wolf Verena , Spuler Simone , Torrente Yvan , Van Tienen Florence ,   Study Group
Published: September 2021

This article will review myogenic cell transplantation for congenital and acquired diseases of skeletal muscle. There are already a number of excellent reviews on this topic, but they are mostly focused on a specific disease, muscular dystrophies and in particular Duchenne Muscular Dystrophy. There are also recent reviews on cell transplantation for inflammatory myopathies, volumetric muscle loss (VML) (this usually with biomaterials), sarcopenia and sphincter incontinence, mainly urinary but also fecal. We believe it would be useful at this stage, to compare the same strategy as adopted in all these different diseases, in order to outline similarities and differences in cell source, pre-clinical models, administration route, and outcome measures. This in turn may help to understand which common or disease-specific problems have so far limited clinical success of cell transplantation in this area, especially when compared to other fields, such as epithelial cell transplantation. We also hope that this may be useful to people outside the field to get a comprehensive view in a single review. As for any cell transplantation procedure, the choice between autologous and heterologous cells is dictated by a number of criteria, such as cell availability, possibility of in vitro expansion to reach the number required, need for genetic correction for many but not necessarily all muscular dystrophies, and immune reaction, mainly to a heterologous, even if HLA-matched cells and, to a minor extent, to the therapeutic gene product, a possible antigen for the patient. Finally, induced pluripotent stem cell derivatives, that have entered clinical experimentation for other diseases, may in the future offer a bank of immune-privileged cells, available for all patients and after a genetic correction for muscular dystrophies and other myopathies.
The Safe Path at the Fork: Ensuring Replication-Associated DNA Double-Strand Breaks are Repaired by Homologous Recombination
Authors: Nickoloff Jac A. , Sharma Neelam , Taylor Lynn , Allen Sage J. , Hromas Robert
Published: September 2021

Cells must replicate and segregate their DNA to daughter cells accurately to maintain genome stability and prevent cancer. DNA replication is usually fast and accurate, with intrinsic (proofreading) and extrinsic (mismatch repair) error-correction systems. However, replication forks slow or stop when they encounter DNA lesions, natural pause sites, and difficult-to-replicate sequences, or when cells are treated with DNA polymerase inhibitors or hydroxyurea, which depletes nucleotide pools. These challenges are termed replication stress, to which cells respond by activating DNA damage response signaling pathways that delay cell cycle progression, stimulate repair and replication fork restart, or induce apoptosis. Stressed forks are managed by rescue from adjacent forks, repriming, translesion synthesis, template switching, and fork reversal which produces a single-ended double-strand break (seDSB). Stressed forks also collapse to seDSBs when they encounter single-strand nicks or are cleaved by structure-specific nucleases. Reversed and cleaved forks can be restarted by homologous recombination (HR), but seDSBs pose risks of mis-rejoining by non-homologous end-joining (NHEJ) to other DSBs, causing genome rearrangements. HR requires resection of broken ends to create 3’ single-stranded DNA for RAD51 recombinase loading, and resected ends are refractory to repair by NHEJ. This Mini Review highlights mechanisms that help maintain genome stability by promoting resection of seDSBs and accurate fork restart by HR.
Bioinformatics Analysis Identified miR-584-5p and Key miRNA-mRNA Networks Involved in the Osteogenic Differentiation of Human Periodontal Ligament Stem Cells
Authors: Wang Chengze , Dong Lingling , Wang Ying , Jiang Zhiwei , Zhang Jing , Yang Guoli
Published: September 2021

Human periodontal ligament cells (PDLCs) play an important role in periodontal tissue stabilization and function. In the process of osteogenic differentiation of PDLSCs, the regulation of molecular signal pathways are complicated. In this study, the sequencing results of three datasets on GEO were used to comprehensively analyze the miRNA-mRNA network during the osteogenic differentiation of PDLSCs. Using the GSE99958 and GSE159507, a total of 114 common differentially expressed genes (DEGs) were identified, including 62 up-regulated genes and 52 down-regulated genes. GO enrichment analysis was performed. The up-regulated 10 hub genes and down-regulated 10 hub genes were screened out by protein-protein interaction network (PPI) analysis and STRING in Cytoscape. Similarly, differentially expressed miRNAs (DEMs) were selected by limma package from GSE159508. Then, using the miRwalk website, we further selected 11 miRNAs from 16 DEMs that may have a negative regulatory relationship with hub genes.In vitroRT-PCR verification revealed that nine DEMs and 18 hub genes showed the same trend as the RNA-seq results during the osteogenic differentiation of PDLSCs. Finally, using miR-584-5p inhibitor and mimics, it was found that miR-584-5p negatively regulates the osteogenic differentiation of PDLSCsin vitro. In summary, the present results found several potential osteogenic-related genes and identified candidate miRNA-mRNA networks for the further study of osteogenic differentiation of PDLSCs.
The 10-Repeat 3′-UTR VNTR Polymorphism in the SLC6A3 Gene May Confer Protection Against Parkinson’s Disease: A Meta-analysis
Authors: Zeng Qiaoli , Ning Fan , Gu Shanshan , Zeng Qiaodi , Chen Riling , Peng Liuquan , Zou Dehua , Ma Guoda , Wang Yajun
Published: September 2021

The dopamine transporter (DAT) is encoded by the SLC6A3 gene and plays an important role in the regulation of the neurotransmitter dopamine. The SLC6A3 gene contains several repetition alleles (3–11 repeats) of a 40-base pair variable number of tandem repeats (VNTR) in the 3′-untranslated region (3′-UTR), which may affect DAT expression levels. The 10-repeat (10R) allele could play a protective role against PD. However, inconsistent findings have been reported.

Methods: A comprehensive meta-analysis was performed to accurately estimate the association between the 10R allele of the 3′-UTR VNTR in SLC6A3 and PD among four different genetic models.

Results: This meta-analysis included a total of 3,142 patients and 3,496 controls. We observed a significant difference between patients and controls for the allele model (10R vs. all others: OR = 0.860, 95% CI: 0.771–0.958, P = 0.006), pseudodominant model (10R/10R + 10R/9R vs. all others: OR = 0.781, 95% CI: 0.641–0.952, P = 0.014) and pseudorecessive model (10R/10R vs. all others: OR = 0.858, 95% CI: 0.760–0.969, P = 0.013) using a fixed effects model. No significant differences were observed under the pseudocodominant model (10R/9R vs. all others: OR = 1.079, 95% CI: 0.945–1.233, P = 0.262). By subgroup analysis, the 10R, 10R/10R and 10R/9R genotypes were found to be significantly different from PD in Asian populations.

Conclusion: Our findings suggest that the SLC6A3 10R may be a protective factor in susceptibility to PD.
Medical Treatment for Endometriosis: Tolerability, Quality of Life and Adherence
Authors: Barbara Giussy , Buggio Laura , Facchin Federica , Vercellini Paolo
Published: September 2021

Endometriosis is associated with painful symptoms, infertility, sexological difficulties, and psychological suffering. All these symptoms have a negative impact on the overall quality of life of women with the disease, with significant personal, social and economic costs. Several medical options are available to manage symptomatic endometriosis. The pharmacological treatment for endometriosis-related pain may be necessary for decades, or at least until there is a desire for pregnancy or physiologic menopause occurs. In this perspective, clinicians should consider not only the efficacy, but also side effects, tolerability, and costs, along with women's preferences toward different treatments. In this mini-review, we analyzed the pros and cons of the available drugs for the medical therapy of endometriosis, such as estrogen-progestins, progestins, GnRH agonist and GnRH antagonists.
SARS-CoV-2 mRNA Vaccines Elicit Different Responses in Immunologically Naïve and Pre-Immune Humans
Authors: Forgacs David , Jang Hyesun , Abreu Rodrigo B. , Hanley Hannah B. , Gattiker Jasper L. , Jefferson Alexandria M. , Ross Ted M.
Published: September 2021

As the COVID-19 pandemic continues, the authorization of vaccines for emergency use has been crucial in slowing down the rate of infection and transmission of the SARS-CoV-2 virus that causes COVID-19. In order to investigate the longitudinal serological responses to SARS-CoV-2 natural infection and vaccination, a large-scale, multi-year serosurveillance program entitled SPARTA (SARS SeroPrevalence and Respiratory Tract Assessment) was initiated at 4 locations in the U.S. The serological assay presented here measuring IgG binding to the SARS-CoV-2 receptor binding domain (RBD) detected antibodies elicited by SARS-CoV-2 infection or vaccination with a 95.5% sensitivity and a 95.9% specificity. We used this assay to screen more than 3100 participants and selected 20 previously infected pre-immune and 32 immunologically naïve participants to analyze their antibody binding to RBD and viral neutralization (VN) responses following vaccination with two doses of either the Pfizer-BioNTech BNT162b2 or the Moderna mRNA-1273 vaccine. Vaccination not only elicited a more robust immune reaction than natural infection, but the level of neutralizing and anti-RBD antibody binding after vaccination is also significantly higher in pre-immune participants compared to immunologically naïve participants (p<0.0033). Furthermore, the administration of the second vaccination did not further increase the neutralizing or binding antibody levels in pre-immune participants (p=0.69). However, ~46% of the immunologically naïve participants required both vaccinations to seroconvert.
Surfaceome Proteomic of Glioblastoma Revealed Potential Targets for Immunotherapy
Authors: Rose Mélanie , Cardon Tristan , Aboulouard Soulaimane , Hajjaji Nawale , Kobeissy Firas , Duhamel Marie , Fournier Isabelle , Salzet Michel
Published: September 2021

Glioblastoma (GBM) is the most common and devastating malignant brain tumor in adults. The mortality rate is very high despite different treatments. New therapeutic targets are therefore highly needed. Cell-surface proteins represent attractive targets due to their accessibility, their involvement in essential signaling pathways, and their dysregulated expression in cancer. Moreover, they are potential targets for CAR-based immunotherapy or mRNA vaccine strategies. In this context, we investigated the GBM-associated surfaceome by comparing it to astrocytes cell line surfaceome to identify new specific targets for GBM. For this purpose, biotinylation of cell surface proteins has been carried out in GBM and astrocytes cell lines. Biotinylated proteins were purified on streptavidin beads and analyzed by shotgun proteomics. Cell surface proteins were identified with Cell Surface Proteins Atlas (CSPA) and Gene Ontology enrichment. Among all the surface proteins identified in the different cell lines we have confirmed the expression of 66 of these in patient’s glioblastoma using spatial proteomic guided by MALDI-mass spectrometry. Moreover, 87 surface proteins overexpressed or exclusive in GBM cell lines have been identified. Among these, we found 11 specific potential targets for GBM including 5 mutated proteins such as RELL1, CYBA, EGFR, and MHC I proteins. Matching with drugs and clinical trials databases revealed that 7 proteins were druggable and under evaluation, 3 proteins have no known drug interaction yet and none of them are the mutated form of the identified proteins. Taken together, we discovered potential targets for immune therapy strategies in GBM.
Effects of Exercise Interventions on Immune Function in Children and Adolescents With Cancer and HSCT Recipients - A Systematic Review
Authors: Beller Ronja , Bennstein Sabrina Bianca , Götte Miriam
Published: September 2021

Background

Pediatric cancer patients are at high risk for life-threatening infections, therapy associated complications and cancer-related side effects. Exercise is a promising tool to support the immune system and reduce inflammation. The primary objective of this systematic review was to evaluate the effects of exercise interventions in pediatric cancer patients and survivors on the immune system.

Methods

For this systematic review (PROSPERO ID: CRD42021194282) we searched four databases (MEDLINE, Cochrane Library, ClinicalTrials.gov, SPORTDiscus) in June 2021. Studies with pediatric patients with oncological disease were included as main criterion. Two authors independently performed data extraction, risk of bias assessment, descriptive analysis and a direction ratio was calculated for all immune cell parameters.

Findings

Of the 1448 detected articles, eight studies with overall n = 400 children and adolescents with cancer and n = 17 healthy children as controls aged 4-19 years met the inclusion criteria. Three randomized, four non-randomized controlled trials and one case series were analyzed descriptively. The exercise interventions had no negative adverse effects on the immune system. Statistically significant results indicated enhanced cytotoxicity through exercise, while changes in immune cell numbers did not differ significantly. Interventions further reduced days of in-hospitalization and reduced the risk of infections. Several beneficial direction ratios in immune parameters were identified favoring the intervention group.

Interpretation

Exercise interventions for pediatric cancer patients and survivors had no negative but promising beneficial effects on the immune system, especially regarding cytotoxicity, but data is very limited. Further research should be conducted on the immunological effects of different training modalities and intensities, during various treatment phases, and for different pediatric cancer types. The direction ratio parameters given here may provide useful guidance for future clinical trials.

Systemic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021194282, Prospero ID: CRD42021194282.
Broadly-Neutralizing Antibodies Against Emerging SARS-CoV-2 Variants
Authors: Shrestha Lok Bahadur , Tedla Nicodemus , Bull Rowena A.
Published: September 2021

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have become a major concern in the containment of current pandemic. The variants, including B.1.1.7 (Alpha), B.1.351 (Beta), P1 (Gamma) and B.1.617.2 (Delta) have shown reduced sensitivity to monoclonal antibodies, plasma and/or sera obtained from convalescent patients and vaccinated individuals. Development of potent therapeutic monoclonal antibodies (mAbs) with broad neutralizing breadth have become a priority for alleviating the devastating effects of this pandemic. Here, we review some of the most promising broadly neutralizing antibodies obtained from plasma of patients that recovered from early variants of SARS-CoV-2 that may be effective against emerging new variants of the virus. This review summarizes several mAbs, that have been discovered to cross-neutralize across Sarbecoviruses and SARS-CoV-2 escape mutants. Understanding the characteristics that confer this broad and cross-neutralization functions of these mAbs would inform on the development of therapeutic antibodies and guide the discovery of second-generation vaccines.
Mannose Treatment: A Promising Novel Strategy to Suppress Inflammation
Authors: Zhang Wei , Cheng Hao , Gui Yuanyuan , Zhan Qipeng , Li Si , Qiao Wenliang , Tong Aiping
Published: September 2021

High glucose and fructose intake have been proven to display pro-inflammatory roles during the progression of inflammatory diseases. However, mannose has been shown to be a special type of hexose that has immune regulatory functions. In this review, we trace the discovery process of the regulatory functions of mannose and summarize some past and recent studies showing the therapeutic functions of mannose in inflammatory diseases. We conclude that treatment with mannose can suppress inflammation by inducing regulatory T cells, suppressing effector T cells and inflammatory macrophages, and increasing anti-inflammatory gut microbiome. By summarizing all the important findings, we highlight that mannose treatment is a safe and promising novel strategy to suppress inflammatory diseases, including autoimmune disease and allergic disease.
Estimating the Abundance of Marine Mammal Populations
Authors: Hammond Philip S. , Francis Tessa B. , Heinemann Dennis , Long Kristy J. , Moore Jeffrey E. , Punt André E. , Reeves Randall R. , Sepúlveda Maritza , Sigurðsson Guðjón Már , Siple Margaret C. , Víkingsson Gísli , Wade Paul R. , Williams Rob , Zerbini Alexandre N.
Published: September 2021

Motivated by the need to estimate the abundance of marine mammal populations to inform conservation assessments, especially relating to fishery bycatch, this paper provides background on abundance estimation and reviews the various methods available for pinnipeds, cetaceans and sirenians. We first give an “entry-level” introduction to abundance estimation, including fundamental concepts and the importance of recognizing sources of bias and obtaining a measure of precision. Each of the primary methods available to estimate abundance of marine mammals is then described, including data collection and analysis, common challenges in implementation, and the assumptions made, violation of which can lead to bias. The main method for estimating pinniped abundance is extrapolation of counts of animals (pups or all-ages) on land or ice to the whole population. Cetacean and sirenian abundance is primarily estimated from transect surveys conducted from ships, small boats or aircraft. If individuals of a species can be recognized from natural markings, mark-recapture analysis of photo-identification data can be used to estimate the number of animals using the study area. Throughout, we cite example studies that illustrate the methods described. To estimate the abundance of a marine mammal population, key issues include: defining the population to be estimated, considering candidate methods based on strengths and weaknesses in relation to a range of logistical and practical issues, being aware of the resources required to collect and analyze the data, and understanding the assumptions made. We conclude with a discussion of some practical issues, given the various challenges that arise during implementation.
Potential Effects of Coronaviruses on the Liver: An Update
Authors: Wang Xinyi , Lei Jianyong , Li Zhihui , Yan Lunan
Published: September 2021

The coronaviruses that cause notable diseases, namely, severe acute respiratory syndrome (SARS), middle east respiratory syndrome (MERS) and coronavirus disease 2019 (COVID-19), exhibit remarkable similarities in genomic components and pathogenetic mechanisms. Although coronaviruses have widely been studied as respiratory tract pathogens, their effects on the hepatobiliary system have seldom been reported. Overall, the manifestations of liver injury caused by coronaviruses typically involve decreased albumin and elevated aminotransferase and bilirubin levels. Several pathophysiological hypotheses have been proposed, including direct damage, immune-mediated injury, ischemia and hypoxia, thrombosis and drug hepatotoxicity. The interaction between pre-existing liver disease and coronavirus infection has been illustrated, whereby coronaviruses influence the occurrence, severity, prognosis and treatment of liver diseases. Drugs and vaccines used for treating and preventing coronavirus infection also have hepatotoxicity. Currently, the establishment of optimized therapy for coronavirus infection and liver disease comorbidity is of significance, warranting further safety tests, animal trials and clinical trials.
Real-Life Retention Rates and Reasons for Switching of Biological DMARDs in Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis
Authors: Bhushan Vandana , Lester Susan , Briggs Liz , Hijjawi Raif , Shanahan E. Michael , Pontifex Eliza , Ninan Jem , Hill Catherine , Cai Fin , Walker Jennifer , Goldblatt Fiona , Wechalekar Mihir D.
Published: September 2021

Aims: To determine real-life biologic/targeted synthetic disease-modifying anti-rheumatic drug (b/tsDMARD) retention rates in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS), explore reasons for switching and to compare results to previously published data.

Methods: Time-to-event analysis for mean treatment duration (estimated as the Restricted Mean Survival Time), b/tsDMARD failure, and b/tsDMARDs switching was performed for 230 patients (n = 147 RA, 46 PsA, 37 AS) who commenced their first b/tsDMARD between 2008 and 2018. Patients were managed in a dedicated “biologics” clinic in a tertiary hospital; the choice of b/tsDMARD was clinician driven based on medical factors and patient preferences. The effect of covariates on switching risk was analysed by a conditional risk-set Cox proportional-hazards model. Treatment retention data was compared to a historical analysis (2002–2008).

Results: The proportions remaining on treatment (retention) were similar, throughout follow-up, for the first, second and third b/tsDMARDs across all patients (p = 0.46). When compared to RA patients, the risk of b/tsDMARD failure was halved in PsA patients [Hazard Ratio (HR) = 0.50], but no different in AS patients (HR = 1.0). The respective restricted mean (95%CI) treatment durations, estimated at 5 years of follow-up, were 3.1 (2.9, 3.4), 4.1 (3.7, 4.6), and 3.3 (2.8, 3.9) years, for RA, PsA, and AS, respectively. Age, gender, disease duration, smoking status and the use of concomitant csDMARDS were not associated with the risk of bDMARD failure. The most common reasons for switching in the first and subsequent years were secondary (n = 62) and primary (n = 35) failure. Comparison with historical data indicated no substantive differences in switching of the first biologic for RA and PsA.

Conclusion: Similar retention rates of the second and third compared to the first b/tsDMARD in RA, PsA, and AS support a strategy of differential b/tsDMARDs use informed by patient presentation. Despite greater availability of b/tsDMARDs with differing mechanisms of action, retention rates of the first b/tsDMARD remain similar to previous years.
Long-Term Impact of Interprofessional Medical Mission Service Trips in Sierra Leone
Authors: Tran Yen , Jarrett Jennie , Gardner Scott , Fernando James , Milliron Mark , Hong Lisa
Published: September 2021

Objective: The purpose of this study was to evaluate the impact of capacity-building short-term mission service trips to Sierra Leone on local health education and perspectives.

Methods: This was a prospective, mixed-methods study. During three mission trips between June 2017 and December 2019, health professional students taught multiple locally selected patient care-related topics. Local staff completed knowledge questionnaires and were surveyed or interviewed on mission service impact along with the cultural competence of missionaries. Mission team members completed the Intercultural Effectiveness Scale (IES) and surveys to determine their cultural competence.

Results: After initial education, 90% passed the knowledge questionnaire with at least a 50% and the correct response rate was 57.9 vs. 66.7% after 6 months and 2.5 years, respectively (p = 0.40). Local staff ranked education/training as most valuable (84%) and highly desired (53%). Mean IES score and survey responses of both missionaries and local staff rated mission team cultural competence as average.

Conclusions: Education-focused mission trips in Sierra Leone seem to have long-lasting benefits and a positive impact on local staff, though improved intercultural competence is needed.
L-Canavanine, a Root Exudate From Hairy Vetch (Vicia villosa) Drastically Affecting the Soil Microbial Community and Metabolite Pathways
Authors: Mardani-Korrani Hossein , Nakayasu Masaru , Yamazaki Shinichi , Aoki Yuichi , Kaida Rumi , Motobayashi Takashi , Kobayashi Masaru , Ohkama-Ohtsu Naoko , Oikawa Yosei , Sugiyama Akifumi , Fujii Yoshiharu
Published: September 2021

L-Canavanine, a conditionally essential non-proteinogenic amino acid analog to L-arginine, plays important roles in cell division, wound healing, immune function, the release of hormones, and a precursor for the synthesis of nitric oxide (NO). In this report, we found that the L-canavanine is released into the soil from the roots of hairy vetch (Vicia villosa) and declines several weeks after growth, while it was absent in bulk proxy. Hairy vetch root was able to exudate L-canavanine in both pots and in vitro conditions in an agar-based medium. The content of the L-canavanine in pots and agar conditions was higher than the field condition. It was also observed that the addition of L-canavanine significantly altered the microbial community composition and diversity in soil. Firmicutes and Actinobacteria became more abundant in the soil after the application of L-canavanine. In contrast, Proteobacteria and Acidobacteria populations were decreased by higher L-canavanine concentration (500 nmol/g soil). Prediction of the soil metabolic pathways using PICRUSt2 estimated that the L-arginine degradation pathway was enriched 1.3-fold when L-canavanine was added to the soil. Results indicated that carbon metabolism-related pathways were altered and the degradation of nitrogen-rich compounds (i.e., amino acids) enriched. The findings of this research showed that secretion of the allelochemical L-canavanine from the root of hairy vetch may alter the soil microbial community and soil metabolite pathways to increase the survival chance of hairy vetch seedlings. This is the first report that L-canavanine acts as an allelochemical that affects the biodiversity of soil microbial community.
Identification and Molecular Characterization of a Novel Hordeivirus Associated With Yellow Mosaic Disease of Privet (Ligustrum vulgare) in Europe
Authors: Reynard Jean-Sébastien , Turco Silvia , Brodard Justine , Kellenberger Isabelle , Maclot François , Schumpp Olivier , Gugerli Paul , Pooggin Mikhail M.
Published: September 2021

Wild plants serve as a large reservoir of known and yet-unknown viruses and as a source of viral pathogens of cultivated plants. Yellow mosaic disease of forest shrub Ligustrum vulgare (privet) was recurrently observed in Europe for more than 100 years. Using a universal virus identification approach based on deep sequencing and de novo assembly of viral small interfering (si)RNAs we identified a causative agent of this disease in Switzerland and reconstructed its complete 3-segmented RNA genome. Notably, a short 3′-terminal common region (CR) attached to each segment via a ∼53–71 nucleotide poly(A) tract, as determined by RT-PCR sequencing, was initially identified as an orphan siRNA contig with conserved tRNA-like secondary structure. Phylogenomic analysis classified this virus as a novel member in the genus Hordeivirus of family Virgaviridae, which we named ligustrum mosaic virus (LigMV). Similar to other hordeiviruses, LigMV formed rod-shape virions (visualized by electron microscopy), was transmitted through seeds and could also be mechanically transmitted to herbaceous hosts Chenopodium quinoa and Nicotiana benthamiana. Blot hybridization analysis identified genomic and subgenomic RNAs, sharing the 3′-CR and likely serving as monocistronic mRNAs for seven evolutionarily-conserved viral proteins including two subunits of viral RNA-dependent RNA polymerase, coat protein, triple gene block proteins mediating viral movement and cysteine-rich suppressor of RNA silencing. Analysis of size, polarity, and hotspot profiles of viral siRNAs suggested that they are produced by the plant antiviral Dicer-like (DCL) proteins DCL2 and DCL4 processing double-stranded intermediates of genomic RNA replication. Whole genome sequencing of French and Austrian isolates of LigMV revealed its genetic stability over a wide geographic range (>99% nucleotide identity to Swiss isolates and each other), suggesting its persistence and spread in Europe via seed dispersal.
Enriched Environment Attenuates Pyroptosis to Improve Functional Recovery After Cerebral Ischemia/Reperfusion Injury
Authors: Liu Jingying , Zheng Jun , Xu Yang , Cao Wenyue , Wang Jinchen , Wang Biru , Zhao Linyao , Zhang Xin , Liao Weijing
Published: September 2021

Enriched environment (EE) is a complex containing social, cognitive, and motor stimuli. Exposure to EE can promote functional recovery after ischemia/reperfusion (I/R) injury. However, the underlying mechanisms remained unclear. Pyroptosis has recently been identified and demonstrated a significant role in ischemic stroke. The purpose of this study was to explore the effect of EE on neuronal pyroptosis after cerebral I/R injury. In the current study, middle cerebral artery occlusion/reperfusion (MCAO/R) was applied to establish the cerebral I/R injury model. Behavior tests including the modified Neurological Severity Scores (mNSS) and the Morris Water Maze (MWM) were performed. The infarct volume was evaluated by Nissl staining. To evaluate the levels of pyroptosis-related proteins, the levels of GSDMD-N and nod-like receptor protein 1/3 (NLRP1/3) inflammasome-related proteins were examined. The mRNA levels of IL-1β and IL-18 were detected by Quantitative Real-Time PCR (qPCR). The secretion levels of IL-1β and IL-18 were analyzed by ELISA. Also, the expression of p65 and p-p65 were detected. The results showed that EE treatment improved functional recovery, reduced infarct volume, attenuated neuronal pyroptosis after cerebral I/R injury. EE treatment also suppressed the activities of NLRP1/NLRP3 inflammasomes. These may be affected by inhabiting the NF-κB p65 signaling pathway. Our findings suggested that neuronal pyroptosis was probably the neuroprotective mechanism that EE treatment rescued neurological deficits after I/R injury.
NSCs Under Strain—Unraveling the Mechanoprotective Role of Differentiating Astrocytes in a Cyclically Stretched Coculture With Differentiating Neurons
Authors: Abraham Jella-Andrea , Blaschke Stefan , Tarazi Samar , Dreissen Georg , Vay Sabine U. , Schroeter Michael , Fink Gereon R. , Merkel Rudolf , Rueger Maria A. , Hoffmann Bernd
Published: September 2021

The neural stem cell (NSC) niche is a highly vascularized microenvironment that supplies stem cells with relevant biological and chemical cues. However, the NSCs’ proximity to the vasculature also means that the NSCs are subjected to permanent tissue deformation effected by the vessels’ heartbeat-induced pulsatile movements. Cultivating NSCs under common culture conditions neglects the—yet unknown—influence of this cyclic mechanical strain on neural stem cells. Under the hypothesis that pulsatile strain should affect essential NSC functions, a cyclic uniaxial strain was applied under biomimetic conditions using an in-house developed stretching system based on cross-linked polydimethylsiloxane (PDMS) elastomer. While lineage commitment remained unaffected by cyclic deformation, strain affected NSC quiescence and cytoskeletal organization. Unexpectedly, cyclically stretched stem cells aligned in stretch direction, a phenomenon unknown for other types of cells in the mammalian organism. The same effect was observed for young astrocytes differentiating from NSCs. In contrast, young neurons differentiating from NSCs did not show mechanoresponsiveness. The exceptional orientation of NSCs and young astrocytes in the stretch direction was blocked upon RhoA activation and went along with a lack of stress fibers. Compared to postnatal astrocytes and mature neurons, NSCs and their young progeny displayed characteristic and distinct mechanoresponsiveness. Data suggest a protective role of young astrocytes in mixed cultures of differentiating neurons and astrocytes by mitigating the mechanical stress of pulsatile strain on developing neurons.
Exploring Peritumoral Neural Tracts by Using Neurite Orientation Dispersion and Density Imaging
Authors: Chong Shin Tai , Liu Xinrui , Kao Hung-Wen , Lin Chien-Yuan Eddy , Hsu Chih-Chin Heather , Kung Yi-Chia , Kuo Kuan-Tsen , Huang Chu-Chung , Lo Chun-Yi Zac , Li Yunqian , Zhao Gang , Lin Ching-Po
Published: September 2021

Diffusion Tensor Imaging (DTI) tractography has been widely used in brain tumor surgery to ensure thorough resection and minimize functional damage. However, due to enhanced anisotropic uncertainty in the area with peritumoral edema, diffusion tractography is generally not practicable leading to high false-negative results in neural tracking. In this study, we evaluated the usefulness of the neurite orientation dispersion and density imaging (NODDI) derived tractography for investigating structural heterogeneity of the brain in patients with brain tumor. A total of 24 patients with brain tumors, characterized by peritumoral edema, and 10 healthy counterparts were recruited from 2014 to 2021. All participants underwent magnetic resonance imaging. Moreover, we used the images obtained from the healthy participants for calibrating the orientation dispersion threshold for NODDI-derived corticospinal tract (CST) reconstruction. Compared to DTI, NODDI-derived tractography has a great potential to improve the reconstruction of fiber tracking through regions of vasogenic edema. The regions with edematous CST in NODDI-derived tractography demonstrated a significant decrease in the intracellular volume fraction (VFic, p < 0.000) and an increase in the isotropic volume fraction (VFiso, p < 0.014). Notably, the percentage of the involved volume of the concealed CST and lesion-to-tract distance could reflect the motor function of the patients. After the tumor resection, four patients with 1–5 years follow-up were showed subsidence of the vasogenic edema and normal CST on DTI tractography. NODDI-derived tractography revealed tracts within the edematous area and could assist neurosurgeons to locate the neural tracts that are otherwise not visualized by conventional DTI tractography.
The Role of β-Carotene in Colonic Inflammation and Intestinal Barrier Integrity
Authors: Cheng Junrui , Balbuena Emilio , Miller Baxter , Eroglu Abdulkerim
Published: September 2021

Background: Carotenoids are naturally occurring pigments accounting for the brilliant colors of fruits and vegetables. They may display antioxidant and anti-inflammatory properties in humans besides being precursors to vitamin A. There is a gap of knowledge in examining their role within colonic epithelial cells. We proposed to address this research gap by examining the effects of a major dietary carotenoid, β-carotene, in the in vitro epithelial cell model.

Methods: We examined the function of β-carotene in the lipopolysaccharide (LPS)/toll-like receptor 4 (TLR4) signaling pathway. We conducted western blotting assays to evaluate expressions of TLR4 and its co-receptor, CD14. We also examined NF-κB p65 subunit protein levels in the model system. Furthermore, we studied the impact of β-carotene on the tight junction proteins, claudin-1, and occludin. We further carried out immunocytochemistry experiments to detect and visualize claudin-1 expression.

Results: β-Carotene reduced LPS-induced intestinal inflammation in colonic epithelial cells. β-Carotene also promoted the levels of tight junction proteins, which might lead to enhanced barrier function.

Conclusions: β-Carotene could play a role in modulating the LPS-induced TLR4 signaling pathway and in enhancing tight junction proteins. The findings will shed light on the role of β-carotene in colonic inflammation and also potentially in metabolic disorders since higher levels of LPS might induce features of metabolic diseases.
Exploring Household Food Dynamics During the COVID-19 Pandemic in Morocco
Authors: El Bilali Hamid , Ben Hassen Tarek , Baya Chatti Chedli , Abouabdillah Aziz , Alaoui Si Bennasseur
Published: September 2021

Alongside the dramatic impact on health systems, eating, shopping, and other food-related habits may have been affected by the COVID-19 crisis. This paper analyses the impacts of the COVID-19 pandemic on food shopping habits and food-related activities of a diverse sample of 340 adult consumers in Morocco. The study is based on an online survey conducted in Morocco from September 15 to November 5, 2020, utilizing a standardized questionnaire delivered in French and Arabic via Survey Monkey. The findings show that consumers' diet, shopping behavior, and food interactions have changed significantly. Indeed, the survey outcomes indicated (i) an increase in the consumption of local items owing to food safety concerns; (ii) an increase in online grocery shopping; (iii) a rise in panic buying and food hoarding; and (iv) an increase in culinary capabilities. The findings are expected to help guide Morocco's current emergency measures as well as long-term food-related policies.
Leptin Receptor-Deficient db/db Mice Show Significant Heterogeneity in Response to High Non-heme Iron Diet
Authors: Paeschke Sabine , Winter Karsten , Bechmann Ingo , Klöting Nora , Blüher Matthias , Baum Petra , Kosacka Joanna , Nowicki Marcin
Published: September 2021

Recent studies have shown an association between iron homeostasis, obesity and diabetes. In this work, we investigated the differences in the metabolic status and inflammation in liver, pancreas and visceral adipose tissue of leptin receptor-deficient db/db mice dependent on high iron concentration diet. 3-month-old male BKS-Leprdb/db/JOrlRj (db/db) mice were divided into two groups, which were fed with different diets containing high iron (29 g/kg, n = 57) or standard iron (0.178 g/kg; n = 42) concentrations for 4 months. As anticipated, standard iron-fed db/db mice developed obesity and diabetes. However, high iron-fed mice exhibited a wide heterogeneity. By dividing into two subgroups at the diabetes level, non-diabetic subgroup 1 (<13.5 mmol/l, n = 30) significantly differed from diabetic subgroup two (>13.5 mmol/l, n = 27). Blood glucose concentration, HbA1c value, inflammation markers interleukin six and tumor necrosis factor α and heme oxygenase one in visceral adipose tissue were reduced in subgroup one compared to subgroup two. In contrast, body weight, C-peptide, serum insulin and serum iron concentrations, pancreatic islet and signal ratio as well as cholesterol, LDL and HDL levels were enhanced in subgroup one. While these significant differences require further studies and explanation, our results might also explain the often-contradictory results of the metabolic studies with db/db mice.