bluuebunny/crossref_metadata_2025 huggingface dataset:
Menaquinone-7 Supplementation Improves Osteogenesis in Pluripotent Stem Cell Derived Mesenchymal Stem Cells
Authors: Akbulut Asim Cengiz , Wasilewski Grzegorz B. , Rapp Nikolas , Forin Francesco , Singer Heike , Czogalla-Nitsche Katrin J. , Schurgers Leon J.
Published: January 2021

Development of clinical stem cell interventions are hampered by immature cell progeny under current protocols. Human mesenchymal stem cells (hMSCs) are characterized by their ability to self-renew and differentiate into multiple lineages. Generating hMSCs from pluripotent stem cells (iPSCs) is an attractive avenue for cost-efficient and scalable production of cellular material. In this study we generate mature osteoblasts from iPSCs using a stable expandable MSC intermediate, refining established protocols. We investigated the timeframe and phenotype of cells under osteogenic conditions as well as the effect of menaquinone-7 (MK-7) on differentiation. From day 2 we noted a significant increase in RUNX2 expression under osteogenic conditions with MK-7, as well as decreases in ROS species production, increased cellular migration and changes to dynamics of collagen deposition when compared to differentiated cells that were not treated with MK-7. At day 21 OsteoMK-7 increased alkaline phosphatase activity and collagen deposition, as well as downregulated RUNX2 expression, suggesting to a mature cellular phenotype. Throughout we note no changes to expression of osteocalcin suggesting a non-canonical function of MK-7 in osteoblast differentiation. Together our data provide further mechanistic insight between basic and clinical studies on extrahepatic activity of MK-7. Our findings show that MK-7 promotes osteoblast maturation thereby increasing osteogenic differentiation.
Fecal Fungal Dysbiosis in Chinese Patients With Alzheimer’s Disease
Authors: Ling Zongxin , Zhu Manlian , Liu Xia , Shao Li , Cheng Yiwen , Yan Xiumei , Jiang Ruilai , Wu Shaochang
Published: January 2021

Gut bacterial dysbiosis plays a vital role in the development of Alzheimer’s disease (AD). However, our understanding of alterations to the gut fungal microbiota and their correlations with host immunity in AD is still limited. Samples were obtained from 88 Chinese patients with AD, and 65 age- and gender-matched, cognitively normal controls. Using these samples, we investigated the fungal microbiota targeting internal transcribed spacer 2 (ITS2) rRNA genes using MiSeq sequencing, and analyzed their associations with the host immune response. Our data demonstrated unaltered fungal diversity but altered taxonomic composition of the fecal fungal microbiota in the AD patients. The analysis of the fungal microbiota was performed using 6,585,557 high-quality reads (2,932,482 reads from the controls and 3,653,075 from the AD patients), with an average of 43,042 reads per sample. We found that several key differential fungi such as Candida tropicalis and Schizophyllum commune were enriched in the AD patients, while Rhodotorula mucilaginosa decreased significantly. Interestingly, C. tropicalis and S. commune were positively correlated with IP-10 and TNF-α levels. In contrast, C. tropicalis was negatively correlated with IL-8 and IFN-γ levels, and R. mucilaginosa was negatively correlated with TNF-α level. PiCRUSt analysis revealed that lipoic acid metabolism, starch and sucrose metabolism were significantly decreased in the AD fungal microbiota. This study is the first to demonstrate fecal fungal dysbiosis in stable AD patients at a deeper level, and to identify the key differential fungi involved in regulating host systemic immunity. The analysis of the fungal microbiota in AD performed here may provide novel insights into the etiopathogenesis of AD and pave the way for improved diagnosis and treatment of AD.
COVID-19 and Acute Coronary Syndromes: Current Data and Future Implications
Authors: Cameli Matteo , Pastore Maria Concetta , Mandoli Giulia Elena , D'Ascenzi Flavio , Focardi Marta , Biagioni Giulia , Cameli Paolo , Patti Giuseppe , Franchi Federico , Mondillo Sergio , Valente Serafina
Published: January 2021

Coronavirus disease-2019 (COVID-19) pandemic is a global healthcare burden, characterized by high mortality and morbidity rates all over the world. During the outbreak period, the topic of acute coronary syndromes (ACS) has raised several clinical issues, due to the risks of COVID-19 induced myocardial injury and to the uncertainties about the management of these cardiologic emergency conditions, which should be organized optimizing the diagnostic and therapeutic resources and ensuring the maximum protection to healthcare personnel and hospital environment. COVID-19 status should be assessed as soon as possible. Moreover, considerably lower rates of hospitalization for ACS have been reported all over the world, due to patients' hesitations to refer to hospital and to missed diagnosis. As a result, short- and long-term complications of myocardial infarction are expected in the near future; therefore, great efforts of healthcare providers will be required to limit the effects of this issue. In the present review we discuss the impact of COVID-19 pandemic on ACS diagnosis and management, with possible incoming consequences, providing an overview of the available evidence and suggesting future changes in social and clinical approach to ACS.
Shedding of Klotho: Functional Implications in Chronic Kidney Disease and Associated Vascular Disease
Authors: Saar-Kovrov Valeria , Donners Marjo M. P. C. , van der Vorst Emiel P. C.
Published: January 2021

α-Klotho (Klotho) exists in two different forms, a membrane-bound and soluble form, which are highly expressed in the kidney. Both forms play an important role in various physiological and pathophysiological processes. Recently, it has been identified that soluble Klotho arises exclusively from shedding or proteolytic cleavage. In this review, we will highlight the mechanisms underlying the shedding of Klotho and the functional effects of soluble Klotho, especially in CKD and the associated cardiovascular complications. Klotho can be cleaved by a process called shedding, releasing the ectodomain of the transmembrane protein. A disintegrin and metalloproteases ADAM10 and ADAM17 have been demonstrated to be mainly responsible for this shedding, resulting in either full-length fragments or sub-fragments called KL1 and KL2. Reduced levels of soluble Klotho have been associated with kidney disease, especially chronic kidney disease (CKD). In line with a protective effect of soluble Klotho in vascular function and calcification, CKD and the reduced levels of soluble Klotho herein are associated with cardiovascular complications. Interestingly, although it has been demonstrated that soluble Klotho has a multitude of effects its direct impact on vascular cells and the exact underlying mechanisms remain largely unknown and should therefore be a major focus of further research. Moreover, functional implications of the cleavage process resulting in KL1 and KL2 fragments remain to be elucidated.
Petrogenesis of Mesoproterozoic Granites of the Swartoup Hills Region, Kakamas Domain, Namaqua Belt, South Africa
Authors: Büttner Steffen Hermann , Prevec Stephen Anthony , Schmeldt Graeme Alvin
Published: January 2021

The Swartoup and Polisiehoek plutons in the Swartoup Hills (South Africa) formed during an episode of significant magma emplacement in the Mesoproterozoic Namaqua Sector of the Namaqua Metamorphic Province. They intruded into mid-crustal metasedimentary rocks of the metapelitic Koenap and mafic to carbonate-bearing Bysteek Formations during and shortly after the ∼1,200–1,220 Ma regional metamorphic peak that reached ultrahigh temperatures. Subsequent to pluton emplacement, the crust underwent regional high-temperature deformation during slow near-isobaric cooling. A further episode of pluton emplacement associated with fluid circulation truncated the first-order regional tectonic structures at ∼1,100 Ma. Based on their petrography, the Swartoup pluton is subdivided into leuco-granitoids with biotite as the sole mafic phase, pyroxene granitoids, and garnet-bearing granitoids, which may contain significant biotite. These subgroups display distinctive geochemical variations from one another, and from the Koenap Formation migmatites and the Polisiehoek granites, which are exposed nearby. Incompatible trace element distributions suggest that the Swartoup and Polisiehoek granitoids represent modified A-type granite magma, consistent with derivation from partial melting of quartzo-feldspathic crust. The magmas incorporated significant amounts of juvenile mantle-derived magma (εNd1200 of ∼−5, and LREE-depleted), but do not require older, early to late Paleoproterozoic crust. Particularly close to contacts to the calcic Bysteek Formation, localized contamination of the Swartoup granites by supracrustal carbonates is evident. A relatively pervasive alkali metasomatic effect is manifested strongly in the initial 87Sr/86Sr and LILE profiles of the Polisiehoek granites in particular, as well as in some of the Swartoup pyroxene granitoids, which could be either a symptom of CO2 metasomatism related to the Bysteek Formation carbonates, or to post-magmatic fluid metasomatism, perhaps linked to regional shearing. The comparison of our results with literature data suggests that similar sources, A-type granitic, Meso- to Paleoproterozoic crustal, and enriched mantle, have contributed, in locally differing proportions, to granites in most parts of the Namaqua Sector. Most likely, these plutons were generated during crustal and mantle melting in a long-lived hot continental back-arc environment.
Correlations Between MRI Biomarkers PDFF and cT1 With Histopathological Features of Non-Alcoholic Steatohepatitis
Authors: Dennis Andrea , Kelly Matt D. , Fernandes Carolina , Mouchti Sofia , Fallowfield Jonathan A. , Hirschfield Gideon , Pavlides Michael , Harrison Stephen , Chakravarthy Manu V. , Banerjee Rajarshi , Sanyal Arun
Published: January 2021

Introduction

Late stage clinical trials in non-alcoholic steatohepatitis (NASH) are currently required by the FDA to use liver biopsy as a primary endpoint. The well-reported limitations with biopsy, such as associated risks and sampling error, coupled with patient preference, are driving investigation into non-invasive alternatives. MRI-derived biomarkers proton density fat fraction (PDFF) and iron-corrected T1 mapping (cT1) are gaining traction as emerging alternatives to biopsy for NASH. Our aim was to explore the correlations between cT1 and PDFF (from LiverMultiScan®), with the histological components on the NAFLD-NASH spectrum in a large cohort of cross-sectional data, in order to calibrate the measurement to histology, and to infer what might constitute a clinically meaningful change when related to the FDA’s criteria.

Materials and Methods

In a retrospective analysis of data combined from three previously published observational NASH studies, in which adult participants who underwent liver biopsy on suspicion of NAFLD or NASH and had an MRI scan measuring cT1 and PDFF (LiverMultiScan®, Perspectum Ltd, UK), associations between imaging biomarkers and histology were tested using Spearman’s rank correlation coefficient (rs), and further exploration of the relationships between the imaging variables and histology were performed using linear regression.

Results

N = 264 patients with mean age of 54 (SD:9.9), 39% female, and 69% with BMI ≥ 30kg.m−2 were included in the analysis. cT1 and PDFF both correlated with all features of the NAFLD activity score (NAS). cT1 was also positively correlated with Kleiner-Brunt fibrosis. Partial correlations, adjusting for steatosis, revealed cT1 correlated with inflammation and fibrosis, whereas PDFF did not, and both were still associated with the NAS, but correlation was weaker with PDFF than cT1. An estimated difference of 88 ms in cT1, or 21% relative difference in PDFF was related to a two-point difference in overall NAS.

Conclusion

The correlations between cT1 and PDFF with the histopathological hallmarks of NASH demonstrate the potential utility of both cT1 and PDFF as non-invasive biomarkers to detect a pharmacodynamic change in NASH, with cT1 showing superiority for detecting changes in inflammation and fibrosis, rather than liver fat alone.
A Diabetic Patient Complicated With Pancreatic Cancer After Using Liraglutide: A Case Report
Authors: Wu Shengjie , Wang Jiabing , Jing Li , Chen Liping
Published: January 2021

Background

Diabetes and cancer are both multifactorial diseases, and epidemiologic evidence indicates that diabetes may be associated with the incidence of certain types of cancer. In diabetes the risk of pancreatic cancer is increased significantly. However, whether certain diabetes treatment being related with the risk of pancreatic cancer remains unclear. In this report, we presented a case of pancreatic ductal adenocarcinoma in a diabetic patient in China after being treated with liraglutide, a novel glucagon-like peptide-1 (GLP-1) analog.

Case report

A 71-year-old Han Chinese man who had had a type 2 diabetes for 25 years presented at the endocrinology department with discomfort in the left upper quadrant of abdomen for 10 days. The patient’s vital signs and laboratory findings were unremarkable except for the elevated level of carbohydrate antigen (CA19-9). The upper abdomen routine enhanced computed tomography (CT) scan showed low density of the pancreatic body and tail, and the histopathological result of the pancreatic biopsy samples was pancreatic ductal adenocarcinoma with regional lymph node metastasis. We reviewed his former medical records and found that liraglutide was added to his hypoglycemic treatment regimen 20 months ago. At that time, the level of tumor biomarkers and upper abdomen routine CT were unremarkable. We estimated the causality between liraglutide and pancreatic cancer by the Naranjo Adverse Drug Reaction Probability scale and WHO-Uppsala Monitoring Centre (WHO-UMC) system, and the causality turned out to be possible.

Conclusion

Our report suggests that liraglutide may be related with the genesis and development of pancreatic cancer and also highlights the importance of regular checkups in diabetic patients treated with liraglutide. However, our report has some notable limitations, and further longer-term follow-up trials with larger sample should be conducted in future to assess the causality between liraglutide and pancreatic cancer.
Effect of N6-Methyladenosine Regulators on Progression and Prognosis of Triple-Negative Breast Cancer
Authors: Wang Shanshan , Zou Xuan , Chen Yajie , Cho William C. , Zhou Xiang
Published: January 2021

Background: The N6-methyladenosine (m6A) modification plays a critical role in cancer development. Little is known about the m6A modification in triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer. Thus, the prognostic value of m6A RNA methylation in TNBC deserves exploration.

Methods: The expression levels of the 13 m6A methylation regulators were compared between the 98 TNBC tumor samples and normal tissue samples based on the transcriptome profiles from The Cancer Genome Atlas (TCGA). The association between the m6A regulators and patients' overall survival was assessed by Kaplan-Meier survival analysis and Cox regression analysis. Lasso regression analysis was conducted to construct a prognostic model based on the m6A methylation system. The prognostic performance of the identified model was validated in GSE88847 and GSE135565 datasets. A nomogram combining the TNM stage and the m6A prognostic model was further constructed for the survival prediction of TNBC patients.

Results: The m6A regulator genes were remarkably dysregulated in TNBC tumor tissues, with ALKBH5, YTHDF2, HNRNPC, KIAA1429, and RBM15 significantly up-regulated and FTO, YTHDC1, YTHDC2, METTL3, METTL14, and ZC3H13 significantly down-regulated (P < 0.01). The expression level of ALKBH5 was an independent unfavorable prognostic factor (HR = 3.327, P = 0.006), while METTL14 (HR = 0.425, P = 0.009) was an independent favorable prognostic factor for TNBC patients. A prognostic model consisting of ALKBH5 and METTL14 was therefore proposed displaying higher accuracy of risk prediction when combined with TNM stage with an AUC of 0.791. The prognostic value of the identified signature remained consistent within the two external validation datasets.

Conclusion: The m6A methylation regulators were significantly dysregulated in TNBC tissues and could constitute a novel prognostic signature for the survival prediction of TNBC patients.
Identification of Gene Signatures and Expression Patterns During Epithelial-to-Mesenchymal Transition From Single-Cell Expression Atlas
Authors: Yu Xiangtian , Pan XiaoYong , Zhang ShiQi , Zhang Yu-Hang , Chen Lei , Wan Sibao , Huang Tao , Cai Yu-Dong
Published: January 2021

Cancer, which refers to abnormal cell proliferative diseases with systematic pathogenic potential, is one of the leading threats to human health. The final causes for patients’ deaths are usually cancer recurrence, metastasis, and drug resistance against continuing therapy. Epithelial-to-mesenchymal transition (EMT), which is the transformation of tumor cells (TCs), is a prerequisite for pathogenic cancer recurrence, metastasis, and drug resistance. Conventional biomarkers can only define and recognize large tissues with obvious EMT markers but cannot accurately monitor detailed EMT processes. In this study, a systematic workflow was established integrating effective feature selection, multiple machine learning models [Random forest (RF), Support vector machine (SVM)], rule learning, and functional enrichment analyses to find new biomarkers and their functional implications for distinguishing single-cell isolated TCs with unique epithelial or mesenchymal markers using public single-cell expression profiling. Our discovered signatures may provide an effective and precise transcriptomic reference to monitor EMT progression at the single-cell level and contribute to the exploration of detailed tumorigenesis mechanisms during EMT.
Gene Editing in Rabbits: Unique Opportunities for Translational Biomedical Research
Authors: Xu Jie , Zhang Jifeng , Yang Dongshan , Song Jun , Pallas Brooke , Zhang Chen , Hu Jiafen , Peng Xuwen , Christensen Neil D. , Han Renzhi , Chen Y. Eugene
Published: January 2021

The rabbit is a classic animal model for biomedical research, but the production of gene targeted transgenic rabbits had been extremely challenging until the recent advent of gene editing tools. More than fifty gene knockout or knock-in rabbit models have been reported in the past decade. Gene edited (GE) rabbit models, compared to their counterpart mouse models, may offer unique opportunities in translational biomedical research attributed primarily to their relatively large size and long lifespan. More importantly, GE rabbit models have been found to mimic several disease pathologies better than their mouse counterparts particularly in fields focused on genetically inherited diseases, cardiovascular diseases, ocular diseases, and others. In this review we present selected examples of research areas where GE rabbit models are expected to make immediate contributions to the understanding of the pathophysiology of human disease, and support the development of novel therapeutics.
Vibrational Spectroscopy: A Valuable Screening and Diagnostic Tool for Obstetric Disorders?
Authors: Richards Oliver , Jenkins Cerys , Griffiths Helena , Paczkowska Edyta , Dunstan Peter R. , Jones Sharon , Morgan Margery , Thomas Tanya , Bowden Jayne , Nakimuli Annettee , Nair Manju , Thornton Catherine A.
Published: January 2021

Preeclampsia (PE) is a common obstetric disorder typically affecting 2–8% of all pregnancies and can lead to several adverse obstetric outcomes for both mother and fetus with the greatest burden of severe outcomes in low middle-income countries (LMICs), therefore, screening for PE is vital. Globally, screening is based on maternal characteristics and medical history which are nonspecific for the disorder. In 2004, the World Health Organization acknowledged that no clinically useful test was able to predict the onset of PE, which prompted a universal search for alternative means of screening. Over the past decade or so, emphasis has been placed on the use of maternal characteristics in conjunction with biomarkers of disease combined into predictive algorithms, however these are yet to transition into the clinic and are cost prohibitive in LMICs. As a result, the screening paradigm for PE remains unchanged. It is evident that novel approaches are needed. Vibrational spectroscopy, specifically Raman spectroscopy and Fourier-transform infrared spectroscopy (FTIR), could provide better alternatives suited for implementation in low resource settings as no specialized reagents are required for conventional approaches and there is a drive to portable platforms usable in both urban and rual community settings. These techniques are based on light scattering and absorption, respectively, allowing detailed molecular analysis of samples to produce a unique molecular fingerprint of diseased states. The specificity of vibrational spectroscopy might well make it suited for application in other obstetric disorders such as gestational diabetes mellitus and obstetric cholestasis. In this review, we summarize current approaches sought as alternatives to current screening methodologies and introduce how vibrational spectroscopy could offer superior screening and diagnostic paradigms in obstetric care. Additionally, we propose a real benefit of such tools in LMICs where limited resources battle the higher prevalence of obstetric disorders.
NLRP3 Inflammasome and Its Critical Role in Gynecological Disorders and Obstetrical Complications
Authors: Fang Xuhui , Wang Yanshi , Zhang Yu , Li Yelin , Kwak-kim Joanne , Wu Li
Published: January 2021

Inflammasomes, intracellular, multimeric protein complexes, are assembled when damage signals stimulate nucleotide-binding oligomerization domain receptors (NLRs). Several inflammasomes have been reported, including the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3), NLRP1, NLRP7, ice protease-activating factor (IPAF), absent in melanoma 2 (AIM2) and NLR family CARD domain-containing protein 4 (NLRC4). Among these inflammasomes, the NLRP3 inflammasome is the most well-studied in terms of structure and function. Unlike other inflammasomes that can only be activated by a finite number of pathogenic microorganisms, the NLRP3 inflammasome can be activated by the imbalance of the internal environment and a large number of metabolites. The biochemical function of NLRP3 inflammasome is to activate cysteine-requiring aspartate proteinase-1 (caspase-1), which converts pro-IL-1β and pro-IL-18 into their active forms, namely, IL-1β and IL-18, which are then released into the extracellular space. The well-established, classic role of NLRP3 inflammasome has been implicated in many disorders. In this review, we discuss the current understanding of NLRP3 inflammasome and its critical role in gynecological disorders and obstetrical complications.
IgE-Mediated Peanut Allergy: Current and Novel Predictive Biomarkers for Clinical Phenotypes Using Multi-Omics Approaches
Authors: Czolk Rebecca , Klueber Julia , Sørensen Martin , Wilmes Paul , Codreanu-Morel Françoise , Skov Per Stahl , Hilger Christiane , Bindslev-Jensen Carsten , Ollert Markus , Kuehn Annette
Published: January 2021

Food allergy is a collective term for several immune-mediated responses to food. IgE-mediated food allergy is the best-known subtype. The patients present with a marked diversity of clinical profiles including symptomatic manifestations, threshold reactivity and reaction kinetics. In-vitro predictors of these clinical phenotypes are evasive and considered as knowledge gaps in food allergy diagnosis and risk management. Peanut allergy is a relevant disease model where pioneer discoveries were made in diagnosis, immunotherapy and prevention. This review provides an overview on the immune basis for phenotype variations in peanut-allergic individuals, in the light of future patient stratification along emerging omic-areas. Beyond specific IgE-signatures and basophil reactivity profiles with established correlation to clinical outcome, allergenomics, mass spectrometric resolution of peripheral allergen tracing, might be a fundamental approach to understand disease pathophysiology underlying biomarker discovery. Deep immune phenotyping is thought to reveal differential cell responses but also, gene expression and gene methylation profiles (eg, peanut severity genes) are promising areas for biomarker research. Finally, the study of microbiome-host interactions with a focus on the immune system modulation might hold the key to understand tissue-specific responses and symptoms. The immune mechanism underlying acute food-allergic events remains elusive until today. Deciphering this immunological response shall enable to identify novel biomarker for stratification of patients into reaction endotypes. The availability of powerful multi-omics technologies, together with integrated data analysis, network-based approaches and unbiased machine learning holds out the prospect of providing clinically useful biomarkers or biomarker signatures being predictive for reaction phenotypes.
The Influence of B Cell Depletion Therapy on Naturally Acquired Immunity to Streptococcus pneumoniae
Authors: Ercoli Giuseppe , Ramos-Sevillano Elisa , Nakajima Rie , de Assis Rafael Ramiro , Jasinskas Algis , Goldblatt David , Felgner Philip , Weckbecker Gisbert , Brown Jeremy
Published: January 2021

The anti-CD20 antibody Rituximab to deplete CD20+ B cells is an effective treatment for rheumatoid arthritis and B cell malignancies, but is associated with an increased incidence of respiratory infections. Using mouse models we have investigated the consequences of B cell depletion on natural and acquired humoral immunity toStreptococcus pneumoniae. B cell depletion of naïve C57Bl/6 mice reduced natural IgM recognition ofS. pneumoniae, but did not increase susceptibility toS. pneumoniaepneumonia. ELISA and flow cytometry assays demonstrated significantly reduced IgG and IgM recognition ofS. pneumoniaein sera from mice treated with B cell depletion prior toS. pneumoniaenasopharyngeal colonization compared to untreated mice. Colonization induced antibody responses to protein rather than capsular antigen, and when measured using a protein array B cell depletion prior to colonization reduced serum levels of IgG to several protein antigens. However, B cell depletedS. pneumoniaecolonized mice were still partially protected against both lung infection and septicemia when challenged withS. pneumoniaeafter reconstitution of their B cells. These data indicate that although B cell depletion markedly impairs antibody recognition ofS. pneumoniaein colonized mice, some protective immunity is maintained, perhaps mediated by cellular immunity.
The Neuroprotective Effect of Short Chain Fatty Acids Against Sepsis-Associated Encephalopathy in Mice
Authors: Liu Jiaming , Jin Yangjie , Ye Yanglie , Tang Yahui , Dai Shanshan , Li Mengfang , Zhao Guangju , Hong Guangliang , Lu Zhong-Qiu
Published: January 2021

Short chain fatty acids (SCFAs) are known to be actively involved in multiple brain disorders, but their roles in sepsis-associated encephalopathy (SAE) remain unclear. Here, we investigated the neuroprotective effects of SCFAs on SAE in mice. Male C57BL/6 mice were intragastrically pretreated with SCFAs for seven successive days, and then subjected to SAE induced by cecal ligation and puncture. The behavioral impairment, neuronal degeneration, and levels of inflammatory cytokines were assessed. The expressions of tight junction (TJ) proteins, including occludin and zoula occludens-1 (ZO-1), cyclooxygenase-2 (COX-2), cluster of differentiation 11b (CD11b), and phosphorylation of JNK and NF-κB p65 in the brain, were measured by western blot and Immunofluorescence analysis. Our results showed that SCFAs significantly attenuated behavioral impairment and neuronal degeneration, and decreased the levels of IL-1β and IL-6 in the brain of SAE mice. Additionally, SCFAs upregulated the expressions of occludin and ZO-1 and downregulated the expressions of COX-2, CD11b, and phosphorylation of JNK and NF-κB p65 in the brain of SAE mice. These findings suggested that SCFAs could exert neuroprotective effects against SAE in mice.
Software-in-the-Loop Combined Reinforcement Learning Method for Dynamic Response Analysis of FOWTs
Authors: Chen Peng , Chen Jiahao , Hu Zhiqiang
Published: January 2021

Floating offshore wind turbines (FOWTs) still face many challenges on how to better predict the dynamic responses. Artificial intelligence (AI) brings a new solution to overcome these challenges with intelligent strategies. A new AI technology-based method, named SADA, is proposed in this paper for the prediction of dynamic responses of FOWTs. Firstly, the methodology of SADA is introduced with the selection of Key Disciplinary Parameters (KDPs). The AI module in SADA was built in a coupled aero-hydro-servo-elastic in-house programDARwindand the policy decision is provided by the machine learning algorithms deep deterministic policy gradient (DDPG). Secondly, a set of basin experimental results of a Hywind Spar-type FOWT were employed to train the AI module. SADA weights KDPs by DDPG algorithms' actor network and changes their values according to the training feedback of 6DOF motions of Hywind platform through comparing theDARwindsimulation results and that of experimental data. Many other dynamic responses that cannot be measured in basin experiment could be predicted in higher accuracy with this intelligentDARwind. Finally, the case study of SADA method was conducted and the results demonstrated that the mean values of the platform's motions can be predicted by AI-basedDARwindwith higher accuracy, for example the maximum error of surge motion is reduced by 21%. This proposed SADA method takes advantage of numerical-experimental method and the machine learning method, which brings a new and promising solution for overcoming the handicap impeding direct use of traditional basin experimental technology in FOWTs design.
Characterizing Community Structure of Benthic Infauna From the Continental Slope of the Southern California Bight
Authors: Gillett David J. , Gilbane Lisa , Schiff Kenneth C.
Published: January 2021

Infauna are an ecologically important component of marine benthic ecosystems and are the most common faunal assemblage used to assess habitat quality. Compared to the shallower waters of the continental shelf, less is known about the benthic fauna from the continental slope, especially how the communities are structured by natural gradients and anthropogenic stressors. The present study was conceived to rectify these data gaps and characterize the natural, baseline structure of the benthic infauna of the upper continental slope (200–100 m) of the Southern California Bight. We aggregated benthic infauna, sediment composition, and sediment chemistry data from different surveys across the Southern California Bight region (750 samples from 347 sites) collected between 1972 and 2016. We defined 208 samples to be in reference condition based upon sediment chemistry and proximity to known anthropogenic disturbances. Cluster analysis of the reference samples was used to identify distinct assemblages and the abiotic characteristics associated with each cluster were then used to define habitat characteristics for each assemblage. Three habitats were identified, delineated by geography, depth, and sediment composition. Across the habitats, there were detectable changes in community composition of the non-disturbed fauna through time. However, the uniqueness of the habitats was persistent, as the fauna from each habitat remained taxonomically distinct from irrespective of the decade of their collection. Within each habitat, subtle, assemblage-scale responses to disturbance could be detected, but no consistent patterns could be identified among the component taxa. As with the non-disturbed samples, there were compositional changes in the fauna of the disturbed samples through time. Despite the changes, fauna from disturbed and non-disturbed samples remained taxonomically distinct from each other within each decade of the dataset. After considering both the spatial and temporal patterns in the fauna of slope ecosystem, it became apparent that there was a high degree of stochasticity in the taxonomic organization of all three habitats. This would suggest that the benthic fauna from these communities may be neutrally organized, which in turn poses interesting challenges for future development of condition assessment tools based upon the benthic fauna in these habitats.
Evaluation of Variable Compressor Technologies
Authors: Grigoriadis Panagiotis , Hoffmann Alexander , La Chi Binh
Published: January 2021

A diverse set of technology solutions are in development for reducing vehicular CO2 emissions. Beside the conventional internal combustion engine, there are hybrid powertrains, fuel cells and full electric vehicles. The challenge is finding the right technology that can be quickly implemented into production as a cost effective solution. In addition to CO2 reduction during vehicle operation, the impact of CO2 in the production and recycling of future vehicles must also be considered. From this perspective, the role of turbocharging is evolving, becoming more important for the future. It is an enabler for mature technologies known to improve engine efficiency like Miller timing, lean burn, increased exhaust gas recirculation (EGR) dilution and exhaust heat recovery. As a boosting device, improved turbocharging can also benefit other powertrain types like fuel cells. All previously mentioned applications benefit from wider compressor maps and higher compressor ratios. To achieve an extension of the performance map to areas of low mass flow rate, different methods have been discussed with the two most promising being trim reduction introduced by IAV’s Variable Trim Compressor (VTC) and swirl generation. The most common device for inducing a swirl onto the incoming airflow is to use swirl generating wings in front of the compressor wheel. However, Iwakiri explained that putting a single plate in front of the compressor wheel disturbs the recirculating flow, which acts positively to extend the compressor map. On this basis, plates were developed that guide the strongly swirled back flowing air in such a way that they impose a swirl on the incoming air. Trim reduction is well known for its ability to shift the surge line and maintain compressor efficiency. To achieve this, a conical element before the compressor wheel guides the incoming flow to the inner area of the wheel resulting in reduced flow separation. An orifice can also achieve almost the same effect but with much less axial extension. The advantages and disadvantages of these measures are explained using numerical (CFD) and experimental (turbocharger test bench) to show the potential of each approach. In summary trim reduction using a conical geometry is still the best performing approach. However, considering package restrictions, an orifice is also a good choice. Whereas swirl producing principles have a moderate impact on shifting the surge line. The extension of high mass flow rate is also of interest and this study shows a simple method to improve the compressor performance map in this area. A combination of the measures to expand the map in both directions is conceivable and is presented here as a concept.
Case Report: Sublingual Microcirculatory Alterations in a Covid-19 Patient With Subcutaneous Emphysema, Venous Thrombosis, and Pneumomediastinum
Authors: Grewal Sanjeev , Harjo Brita , Aykut Güclü , Ergin Bülent , Nowitzky Ralph , Ince Can , Akin Sakir
Published: January 2021

The Corona virus disease 2019 (Covid-19) has brought a wide range of challenges in intensive care medicine. Understanding of the pathophysiology of Covid-19 relies on interpreting of its impact on the vascular, particularly microcirculatory system. Herein we report on the first use of the latest generation hand-held vital microscope to evaluate the sublingual microcirculation in a Covid-19 patient with subcutaneous emphysema, venous thrombosis and pneumomediastinum. Remarkably, microcirculatory parameters of the patient were increased during the exacerbation period, which is not a usual finding in critically ill patients mostly presenting with a loss of hemodynamic coherence. In contrast, recovery from the disease led to a subsequent amelioration of these parameters. This report clearly shows the importance of microcirculatory monitoring for evaluating the course and the adequacy of therapy in Covid-19 patients.
Effect of Convalescent Plasma in Critically Ill Patients With COVID-19: An Observational Study
Authors: Kurtz Pedro , Righy Cassia , Gadelha Monica , Bozza Fernando A. , Bozza Patricia T. , Gonçalves Bruno , Bastos Leonardo S. L. , Vale Andre M. , Higa Luiza M. , Castilho Leda , Monteiro Fabio L. , Charris Nestor , Fialho Fernanda , Turon Ricardo , Guterres Alexandro , Lyra Miranda Renan , de Azeredo Lima Carlos Henrique , de Caro Vanessa , Prazeres Marco Aurelio , Ventura Nina , Gaspari Clara , Miranda Fabio , Jose da Mata Paulo , Pêcego Margarida , Mateos Sheila , Lopes Maria Esther , Castilho Shirley , Oliveira Álvaro , Boquimpani Carla , Rabello Andréa , Lopes Josiane , Neto Orlando Conceição , Ferreira Orlando da C. , Tanuri Amilcar , Filho Paulo Niemeyer , Amorim Luiz
Published: January 2021

Background: Convalescent plasma is a potential therapeutic option for critically ill patients with coronavirus disease 19 (COVID-19), yet its efficacy remains to be determined. The aim was to investigate the effects of convalescent plasma (CP) in critically ill patients with COVID-19.

Methods: This was a single-center prospective observational study conducted in Rio de Janeiro, Brazil, from March 17th to May 30th, with final follow-up on June 30th. We included 113 laboratory-confirmed COVID-19 patients with respiratory failure. Primary outcomes were time to clinical improvement and survival within 28 days. Secondary outcomes included behavior of biomarkers and viral loads. Kaplan–Meier analyses and Cox proportional-hazards regression using propensity score with inverse-probability weighing were performed.

Results: 41 patients received CP and 72 received standard of care (SOC). Median age was 61 years (IQR 48–68), disease duration was 10 days (IQR 6–13), and 86% were mechanically ventilated. At least 29 out of 41CP-recipients had baseline IgG titers ≥ 1:1,080. Clinical improvement within 28 days occurred in 19 (46%) CP-treated patients, as compared to 23 (32%) in the SOC group [adjusted hazard ratio (aHR) 0.91 (0.49–1.69)]. There was no significant change in 28-day mortality (CP 49% vs. SOC 56%; aHR 0.90 [0.52–1.57]). Biomarker assessment revealed reduced inflammatory activity and increased lymphocyte count after CP.

Conclusions: In this study, CP was not associated with clinical improvement or increase in 28-day survival. However, our study may have been underpowered and included patients with high IgG titers and life-threatening disease.

Clinical Trial Registration: The study protocol was retrospectively registered at the Brazilian Registry of Clinical Trials (ReBEC) with the identification RBR-4vm3yy (http://www.ensaiosclinicos.gov.br).
Prevalence of Naturally-Occurring NS5A and NS5B Resistance-Associated Substitutions in Iranian Patients With Chronic Hepatitis C Infection
Authors: Rahimi Pooneh , Sharafi Heidar , Bahramali Golnaz , SajadianFard FaridehSadat , Asadi Nafiseh Sadat , Alavian Seyed Moayed , Iranpur Mobarakeh Vahid , Moravej Seyedeh Zahra
Published: January 2021

Background

Hepatitis C virus (HCV), non-structural 5A (NS5A), and non-structural 5B (NS5B) resistance-associated substitutions (RASs) are the main causes of failure to direct-acting antiviral agents (DAAs). NS5A and NS5B RASs can occur in patients with HCV infection naturally and before exposure to DAAs.

Objectives

This study aimed to evaluate naturally-occurring NS5A and NS5B RASs in Iranian patients with HCV genotype 1a (HCV-1a) and -3a infections.

Methods

In this cross-sectional study, viral RNA was extracted from serum specimens. NS5A and NS5B regions were amplified using RT-PCR followed by DNA sequencing. The results of nucleotide sequences were aligned against reference sequences of HCV-1a and -3a and the amino acid substitutions were analyzed using geno2pheno [hcv] web application.

Results

Among 135 patients with hepatitis C, NS5A amino acid substitutions/RASs were identified in 26.4% and 15.9% of patients with HCV-1a and -3a infections, respectively. The identified amino acid substitutions/RASs in the NS5A region of patients with HCV-1a infection were M28T/V/I 11.1%, Q30R/H 4.2%, L31M 1.4%, and H58Y/P/C/D/Q/S/T 16.7%. Y93H substitution was not found in HCV-1a sequences. In patients with HCV-3a infection, NS5A amino acid substitutions/RASs were A30T/K 9.5%, L31F 1.6%, P58S/T/C 3.2%, Y93H 3.2%, and Y93N 3.2%. No resistance substitutions were identified in NS5B sequences from patients with HCV-1a and -3a infections.

Conclusion

In this study, baseline amino acid substitutions/RASs were only identified in the NS5A region in Iranian patients with HCV-1a and -3a infections, and the prevalence of these amino acid substitutions/RASs were in accordance with similar studies. There were no RASs in the HCV-1a and -3a NS5B region.
Identification of Vibrio parahaemolyticus and Vibrio spp. Specific Outer Membrane Proteins by Reverse Vaccinology and Surface Proteome
Authors: Wang Wenbin , Liu Jianxin , Guo Shanshan , Liu Lei , Yuan Qianyun , Guo Lei , Pan Saikun
Published: January 2021

The discovery of outer membrane proteins (OMPs) with desirable specificity and surface availability is a fundamental challenge to develop accurate immunodiagnostic assay and multivalent vaccine of pathogenic Vibrio species in food and aquaculture. Herein 101 OMPs were systemically screened from 4,831 non-redundant proteins of Vibrio parahaemolyticus by bioinformatical predication of signaling peptides, transmembrane (TM) α-helix, and subcellular location. The sequence homology analysis with 32 species of Vibrio spp. and all the non-Vibrio strains revealed that 15 OMPs were conserved in at least 23 Vibrio species, including BamA (VP2310), GspD (VP0133), Tolc (VP0425), OmpK (VP2362), OmpW (VPA0096), LptD (VP0339), Pal (VP1061), flagellar L-ring protein (VP0782), flagellar protein MotY (VP2111), hypothetical protein (VP1713), fimbrial assembly protein (VP2746), VacJ lipoprotein (VP2214), agglutination protein (VP1634), and lipoprotein (VP1267), Chitobiase (VP0755); high adhesion probability of flgH, LptD, OmpK, and OmpW indicated they were potential multivalent Vibrio vaccine candidates. V. parahaemolyticus OMPs were found to share high homology with at least one or two Vibrio species, 19 OMPs including OmpA like protein (VPA073), CsuD (VPA1504), and MtrC (VP1220) were found relatively specific to V. parahaemolyticus. The surface proteomic study by enzymatical shaving the cells showed the capsular polysaccharides most likely limited the protease action, while the glycosidases improved the availability of OMPs to trypsin. The OmpA (VPA1186, VPA0248, VP0764), Omp (VPA0166), OmpU (VP2467), BamA (VP2310), TolC (VP0425), GspD (VP0133), OmpK (VP2362), lpp (VPA1469), Pal (VP1061), agglutination protein (VP1634), and putative iron (III) compound receptor (VPA1435) have better availability on the cell surface.
Temporal Dynamics of Cloacal Microbiota in Adult Laying Chickens With and Without Access to an Outdoor Range
Authors: Schreuder Janneke , Velkers Francisca C. , Bossers Alex , Bouwstra Ruth J. , de Boer Willem F. , van Hooft Pim , Stegeman J. Arjan , Jurburg Stephanie D.
Published: January 2021

Associations between animal health and performance, and the host’s microbiota have been recently established. In poultry, changes in the intestinal microbiota have been linked to housing conditions and host development, but how the intestinal microbiota respond to environmental changes under farm conditions is less well understood. To gain insight into the microbial responses following a change in the host’s immediate environment, we monitored four indoor flocks of adult laying chickens three times over 16 weeks, during which two flocks were given access to an outdoor range, and two were kept indoors. To assess changes in the chickens’ microbiota over time, we collected cloacal swabs of 10 hens per flock and performed 16S rRNA gene amplicon sequencing. The poultry house (i.e., the stable in which flocks were housed) and sampling time explained 9.2 and 4.4% of the variation in the microbial community composition of the flocks, respectively. Remarkably, access to an outdoor range had no detectable effect on microbial community composition, the variability of microbiota among chickens of the same flock, or microbiota richness, but the microbiota of outdoor flocks became more even over time. Fluctuations in the composition of the microbiota over time within each poultry house were mainly driven by turnover in rare, rather than dominant, taxa and were unique for each flock. We identified 16 amplicon sequence variants that were differentially abundant over time between indoor and outdoor housed chickens, however none were consistently higher or lower across all chickens of one housing type over time. Our study shows that cloacal microbiota community composition in adult layers is stable following a sudden change in environment, and that temporal fluctuations are unique to each flock. By exploring microbiota of adult poultry flocks within commercial settings, our study sheds light on how the chickens’ immediate environment affects the microbiota composition.