bluuebunny/crossref_metadata_2025 huggingface dataset:
Planning and Evaluating Remote Consultation Services: A New Conceptual Framework Incorporating Complexity and Practical Ethics
Authors: Greenhalgh Trisha , Rosen Rebecca , Shaw Sara E. , Byng Richard , Faulkner Stuart , Finlay Teresa , Grundy Emily , Husain Laiba , Hughes Gemma , Leone Claudia , Moore Lucy , Papoutsi Chrysanthi , Pope Catherine , Rybczynska-Bunt Sarah , Rushforth Alexander , Wherton Joseph , Wieringa Sietse , Wood Gary W.
Published: August 2021

Establishing and running remote consultation services is challenging politically (interest groups may gain or lose), organizationally (remote consulting requires implementation work and new roles and workflows), economically (costs and benefits are unevenly distributed across the system), technically (excellent care needs dependable links and high-quality audio and images), relationally (interpersonal interactions are altered), and clinically (patients are unique, some examinations require contact, and clinicians have deeply-held habits, dispositions and norms). Many of these challenges have an under-examined ethical dimension. In this paper, we present a novel framework, Planning and Evaluating Remote Consultation Services (PERCS), built from a literature review and ongoing research. PERCS has 7 domains—the reason for consulting, the patient, the clinical relationship, the home and family, technologies, staff, the healthcare organization, and the wider system—and considers how these domains interact and evolve over time as a complex system. It focuses attention on the organization's digital maturity and digital inclusion efforts. We have found that both during and beyond the pandemic, policymakers envisaged an efficient, safe and accessible remote consultation service delivered through state-of-the art digital technologies and implemented via rational allocation criteria and quality standards. In contrast, our empirical data reveal that strategic decisions about establishing remote consultation services, allocation decisions for appointment type (phone, video, e-, face-to-face), and clinical decisions when consulting remotely are fraught with contradictions and tensions—for example, between demand management and patient choice—leading to both large- and small-scale ethical dilemmas for managers, support staff, and clinicians. These dilemmas cannot be resolved by standard operating procedures or algorithms. Rather, they must be managed by attending to here-and-now practicalities and emergent narratives, drawing on guiding principles applied with contextual judgement. We complement the PERCS framework with a set of principles for informing its application in practice, including education of professionals and patients.
The Pseudo-Laplace Filter for Vector-Based Elastic Reverse Time Migration
Authors: Du Qizhen , Zhang Xiaoyu , Zhang Shukui , Zhang Fuyuan , Fu Li-Yun
Published: August 2021

The scalar images (PP and PS) can be effectively obtained in vector-based elastic reverse time migration by applying dot product–based scalar imaging conditions to the separated vector wavefields. However, the PP image suffers from polarity reversal issues when opening angles are greater than 90∘ and backscattering artifacts when opening angles are close to 180∘. To address these issues, we propose the pseudo-Laplace filter for the dot product–based scalar imaging condition. Based on the analysis of the Laplace filter in the scalar image of vector-based wavefields, the second-order parallel-oriented partial derivatives of Cartesian components cross-correlation results are selected to construct the pseudo-Laplace filter. In contrast, second-order normal-oriented partial derivatives of the Cartesian component’s cross-correlation results are omitted. The theoretical analysis with the plane wave assumption shows that the proposed pseudo-Laplace filter can solve the problems of backscattering artifacts and polarity reversal in PP images by the scalar imaging condition. Due to additional polarity correction and backscattering attenuation, numerical examples show excellent performance in PP images with a pseudo-Laplace filter. Furthermore, the application of the pseudo-Laplace filter requires trivial additional computation or storage.
Estimates of Type 2 Diabetes Mellitus Burden Attributable to Particulate Matter Pollution and Its 30-Year Change Patterns: A Systematic Analysis of Data From the Global Burden of Disease Study 2019
Authors: Wu Ying , Fu Rongguo , Lei Chen , Deng Yujiao , Lou Weiyang , Wang Li , Zheng Yi , Deng Xinyue , Yang Si , Wang Meng , Zhai Zhen , Zhu Yuyao , Xiang Dong , Hu Jingjing , Dai Zhijun , Gao Jie
Published: August 2021

Background

Epidemiological trends of type 2 diabetes mellitus attributable to fine particulate matter (PM2.5) pollution remain unclear. Here, we estimated spatiotemporal trends of type 2 diabetes mellitus burden attributable to PM2.5 pollution, including ambient particulate matter pollution (APMP) and household air pollution (HAP), from 1990–2019.

Methods

Data were obtained from the Global Burden of Disease Study 2019 and were analyzed by age, sex, year, and location. Joinpoint regression analysis was applied in the analysis of temporal trends in type 2 diabetes mellitus burden over the 30 years.

Results

Globally, PM2.5 pollution contributed to 292.5 thousand deaths and 13 million disability-adjusted life-years (DALYs) in 2019. APMP ranked third among all risk factors, causing an increase in type 2 diabetes mellitus burden from 1990, whereas the impact of HAP significantly fell during the same period. Both APMP and HAP contributed the most to deaths and DALYs of type 2 diabetes mellitus among older people. However, the age-standardized death and DALY rates of type 2 diabetes mellitus attributable to APMP were greater among males and people in the middle socio-demographic index countries, especially in Southern Sub-Saharan Africa. For HAP, type 2 diabetes mellitus burden was modestly higher in females and was highest in Oceania, which was the only region with an increase from 1990.

Conclusions

PM2.5 pollution resulted in substantial and increasing type 2 diabetes mellitus burden worldwide. Hence, governments and health systems should take steps to reduce air pollution to mitigate this increasing burden.
Gas Discharge Resistance and Medium Damage Degree as Hydrate Dissociation at Different Ambient Conditions
Authors: Chen Xueping , Zhang Peng , Wu Qingbai , Zhang Lianhai , Li Shuaijun , Zhan Jing , Wang Yingmei
Published: August 2021

For the investigation on some hydrate dissociation behaviors at different ambient conditions, methane hydrates formed inside porous media with different saturations were dissociated by depressurizations. Plots of the instantaneous flow rate of gas as dissociation versus production pressure as well as deformation of experimental sample versus accumulative amount of released gas were drawn. These two lines slopes are, respectively, characterized as gas discharge resistance and reciprocal of the latter one as damage degree of experimental samples. The results show that these formed hydrates at higher ambient conditions, that is, temperature and pressure, and possess a higher saturation, which is beneficial to discharge gas and to keep experimental samples undamaged. And the nonuniformity of dissociation processes at different layer positions induced by depressurization is inhibited significantly, especially while combining extra heating. Hydrate saturation dominates the total volume loss of these samples under loadings. These conclusions can provide reference for the prediction in gas discharge capability and media damage degree as hydrate dissociation at different experimental and natural ambient conditions.
Comparative Analyses of Gene Co-expression Networks: Implementations and Applications in the Study of Evolution
Authors: Ovens Katie , Eames B. Frank , McQuillan Ian
Published: August 2021

Similarities and differences in the associations of biological entities among species can provide us with a better understanding of evolutionary relationships. Often the evolution of new phenotypes results from changes to interactions in pre-existing biological networks and comparing networks across species can identify evidence of conservation or adaptation. Gene co-expression networks (GCNs), constructed from high-throughput gene expression data, can be used to understand evolution and the rise of new phenotypes. The increasing abundance of gene expression data makes GCNs a valuable tool for the study of evolution in non-model organisms. In this paper, we cover motivations for why comparing these networks across species can be valuable for the study of evolution. We also review techniques for comparing GCNs in the context of evolution, including local and global methods of graph alignment. While some protein-protein interaction (PPI) bioinformatic methods can be used to compare co-expression networks, they often disregard highly relevant properties, including the existence of continuous and negative values for edge weights. Also, the lack of comparative datasets in non-model organisms has hindered the study of evolution using PPI networks. We also discuss limitations and challenges associated with cross-species comparison using GCNs, and provide suggestions for utilizing co-expression network alignments as an indispensable tool for evolutionary studies going forward.
Growth Differentiation Factor 15 Is Associated With Alzheimer’s Disease Risk
Authors: Wu Peng-Fei , Zhang Xing-Hao , Zhou Ping , Yin Rui , Zhou Xiao-Ting , Zhang Wan
Published: August 2021

Background

Previous observational studies have suggested that associations exist between growth differentiation factor 15 (GDF-15) and neurodegenerative diseases. We aimed to investigate the causal relationships between GDF-15 and Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS).

Methods

Using summary-level datasets from genome-wide association studies of European ancestry, we performed a two-sample Mendelian randomization (MR) study. Genetic variants significantly associated (p < 5 × 10–8) with GDF-15 were selected as instrumental variables (n = 5). An inverse-variance weighted method was implemented as the primary MR approach, while weighted median, MR–Egger, leave-one-out analysis, and Cochran’s Q-test were conducted as sensitivity analyses. All analyses were performed using R 3.6.1 with relevant packages.

Results

MR provided evidence for the association of elevated GDF-15 levels with a higher risk of AD (odds ratio = 1.14; 95% confidence interval, 1.04–1.24; p = 0.004). In the reverse direction, Mendelian randomization suggested no causal effect of genetically proxied risk of AD on circulating GDF-15 (p = 0.450). The causal effects of GDF-15 on PD (p = 0.597) or ALS (p = 0.120) were not identified, and the MR results likewise did not support the association of genetic liability to PD or ALS with genetically predicted levels of GDF-15. No evident heterogeneity or horizontal pleiotropy was revealed by multiple sensitivity analyses.

Conclusion

We highlighted the role of GDF-15 in AD as altogether a promising diagnostic marker and a therapeutic target.
Genetic Diversity of MHC B-F/B-L Region in 21 Chicken Populations
Authors: Yuan Yiming , Zhang Huanmin , Yi Guoqiang , You Zhen , Zhao Chunfang , Yuan Haixu , Wang Kejun , Li Junying , Yang Ning , Lian Ling
Published: August 2021

The chicken major histocompatibility complex (MHC) on chromosome 16 is the most polymorphic region across the whole genome, and also an ideal model for genetic diversity investigation. The MHC B-F/B-L region is 92 kb in length with high GC content consisting of 18 genes and one pseudogene (Blec4), which plays important roles in immune response. To evaluate polymorphism of the Chinese indigenous chickens as well as to analyze the effect of selection to genetic diversity, we used WaferGen platform to identify sequence variants of the B-F/B-L region in 21 chicken populations, including the Red Jungle Fowl (RJF), Cornish (CS), White Leghorns (WLs), 16 Chinese domestic breeds, and two well-known inbred lines 63 and 72. A total of 3,319 single nucleotide polymorphism (SNPs) and 181 INDELs in the B-F/B-L region were identified among 21 populations, of which 2,057 SNPs (62%) and 159 INDELs (88%) were novel. Most of the variants were within the intron and the flanking regions. The average variation density was 36 SNPs and 2 INDELs per kb, indicating dramatical high diversity of this region. Furthermore, BF2 was identified as the hypervariable genes with 67 SNPs per kb. Chinese domestic populations showed higher diversity than the WLs and CS. The indigenous breeds, Nandan Yao (NY), Xishuangbanna Game (XG), Gushi (GS), and Xiayan (XY) chickens, were the top four with the highest density of SNPs and INDELs. The highly inbred lines 63 and 72 have the lowest diversity, which might be resulted from a long-term intense selection for decades. Collectively, we refined the genetic map of chicken MHC B-F/B-L region, and illustrated genetic diversity of 21 chicken populations. Abundant genetic variants were identified, which not only strikingly expanded the current Ensembl SNP database, but also provided comprehensive data for researchers to further investigate association between variants in MHC and immune traits.
Quality of Care in Family Planning Services: Differences Between Formal and Informal Settlements of Kira Municipality, Uganda
Authors: Lukyamuzi Zubair , Tetui Moses , Fonseca-Rodríguez Osvaldo , Atuyambe Lynn , Makumbi Fredrick Edward , Baroudi Mazen
Published: August 2021

Background: Quality of care (QoC) of family planning (FP) affects contraceptive use, and it varies across types of urban settlement. This study assesses the difference in service delivery point (SDP) structural and process factors between formal and informal urban settlements, and the opinion of the client on the QoC in informal settlements. This is useful in creating an evidence base to advocate for better quality services for the most vulnerable in society.

Methods: This was a cross-sectional survey that included SDPs of Kira municipality in Wakiso district, Uganda. Data were collected from all the service points in Kira municipality with the caretakers consented. In addition, using multi-stage sampling, 626 women of reproductive age (15–49 years) who lived in the informal settlements of Kira municipality were interviewed. Data were collected using structured questionnaires, descriptive analysis was carried out in Stata version 14.0, and Chi-square and t-tests were used to compare the informal with the formal settlements.

Results: Formal settlements generally had more higher-level SDPs compared to informal settlements (value of p < 0.001). SDPs in the formal settlements provided more FP methods and had more community health workers (CHW) to support their work. Also, SDPs in the formal settlements were more likely to have long-term FP methods available and more likely to have trained personnel to insert and remove implants and IUDs compared to those in informal settlements. Additionally, more SDPs in the formal settlements provided counseling for permanent, long-term, and short-term FP methods. Of the 626 interviewed women, most of the women (68.6%) reported that they would not return to the previous FP provider or refer a friend to the same provider (72.7%).

Conclusions: There is a lower quality FP services in the informal settlements with a commensurable effect on the client satisfaction with the services. Therefore, improving the quality of FP services in informal settlements should be a top priority. Improved quality of services could act as a motivation to increase the uptake of modern contraceptives in such settings.
Clinical Application of Metagenomic Next-Generation Sequencing for Suspected Infections in Patients With Primary Immunodeficiency Disease
Authors: Tang Wenjing , Zhang Yu , Luo Chong , Zhou Lina , Zhang Zhiyong , Tang Xuemei , Zhao Xiaodong , An Yunfei
Published: August 2021

Background

Infections are the major cause of morbidity and mortality in patients with primary immunodeficiency disease (PID). Timely and accurate microbiological diagnosis is particularly important in these patients. Metagenomic next-generation sequencing (mNGS) has been used for pathogen detection recently. However, few reports describe the use of mNGS for pathogen identification in patients with PID.

Objective

To evaluate the utility of mNGS for detecting pathogens in patients with PID, and to compare it with conventional microbiological tests (CMT).

Methods

This single center retrospective study investigated the diagnostic performance of mNGS for pathogens detection in PID patients and compared it with CMT. Sixteen PID patients with suspected infection were enrolled, and medical records were analyzed to extract detailed clinical characteristics such as gene variation, immune status, microbial distribution, time-consuming of mNGS and CMT, treatment, and outcomes.

Results

mNGS identified pathogenic microbe in 93.75% samples, compared to 31.25% for culture and 68.75% for conventional methods, and detected an extra 18 pathogenic microorganisms including rare opportunistic pathogens and Mycobacterium tuberculosis. Pathogen identification by mNGS required 48 hours, compared with bacterial culture for 3-7 days and even longer for fungus and Mycobacterium tuberculosis culture.

Conclusions

mNGS has marked advantages over conventional methods for pathogenic diagnosis, particularly opportunistic pathogens and mixed infections, in patients with PID. This method might enable clinicians to make more timely and targeted therapeutic decisions, thereby improving the prognosis of these patients.
Neutrophil Myeloperoxidase Derived Chlorolipid Production During Bacteria Exposure
Authors: Amunugama Kaushalya , Kolar Grant R. , Ford David A.
Published: August 2021

Neutrophils are the most abundant white blood cells recruited to the sites of infection and inflammation. During neutrophil activation, myeloperoxidase (MPO) is released and converts hydrogen peroxide to hypochlorous acid (HOCl). HOCl reacts with plasmalogen phospholipids to liberate 2-chlorofatty aldehyde (2-ClFALD), which is metabolized to 2-chlorofatty acid (2-ClFA). 2-ClFA and 2-ClFALD are linked with inflammatory diseases and induce endothelial dysfunction, neutrophil extracellular trap formation (NETosis) and neutrophil chemotaxis. Here we examine the neutrophil-derived chlorolipid production in the presence of pathogenic E. coli strain CFT073 and non-pathogenic E. coli strain JM109. Neutrophils cocultured with CFT073 E. coli strain and JM109 E. coli strain resulted in 2-ClFALD production. 2-ClFA was elevated only in CFT073 coculture. NETosis is more prevalent in CFT073 cocultures with neutrophils compared to JM109 cocultures. 2-ClFA and 2-ClFALD were both shown to have significant bactericidal activity, which is more severe in JM109 E. coli. 2-ClFALD metabolic capacity was 1000-fold greater in neutrophils compared to either strain of E. coli. MPO inhibition reduced chlorolipid production as well as bacterial killing capacity. These findings indicate the chlorolipid profile is different in response to these two different strains of E. coli bacteria.
Elimination of SHIV Infected Cells by Combinations of Bispecific HIVxCD3 DART® Molecules
Authors: Tuyishime Marina , Dashti Amir , Faircloth Katelyn , Jha Shalini , Nordstrom Jeffrey L. , Haynes Barton F. , Silvestri Guido , Chahroudi Ann , Margolis David M. , Ferrari Guido
Published: August 2021

Bispecific HIVxCD3 DART molecules that co-engage the viral envelope glycoprotein (Env) on HIV-1-infected cells and the CD3 receptor on CD3+ T cells are designed to mediate the cytolysis of HIV-1-infected, Env-expressing cells. Using a novelex vivosystem with cells from rhesus macaques (RMs) infected with a chimeric Simian-Human Immunodeficiency Virus (SHIV) CH505 and maintained on ART, we tested the ability of HIVxCD3 DART molecules to mediate elimination ofin vitro-reactivated CD4+ T cells in the absence or presence of autologous CD8+ T cells. HIVxCD3 DART molecules with the anti-HIV-1 Env specificities of A32 or 7B2 (non-neutralizing antibodies) or PGT145 (broadly neutralizing antibody) were evaluated individually or combined. DART molecule-mediated antiviral activity increased significantly in the presence of autologous CD8+ T cells. In thisex vivosystem, the PGT145 DART molecule was more active than the 7B2 DART molecule, which was more active than the A32 DART molecule. A triple combination of the DART molecules exceeded the activity of the individual PGT145 DART molecule. Modified quantitative virus outgrowth assays confirmed the ability of the DART molecules to redirect RM CD3+ T cells to eliminate SHIV-infected RM CD4+ T cells as demonstrated by the decreased propagation ofin vitroinfection by the infected cells pre-incubated with DART molecules in presence of effector CD8+ T cells. While mediating cytotoxic activity, DART molecules did not increase proinflammatory cytokine production. In summary, combination of HIVxCD3 DART molecules that have broadly-neutralizing and non-neutralizing anti-HIV-1 Env specificities can leverage the host immune system for treatment of HIV-1 infection but will require appropriate reactivation of the latent reservoir.
A Robust Hypoxia Risk Score Predicts the Clinical Outcomes and Tumor Microenvironment Immune Characters in Bladder Cancer
Authors: Liu Zhi , Tang Qiao , Qi Tiezheng , Othmane Belaydi , Yang Zhe , Chen Jinbo , Hu Jiao , Zu Xiongbing
Published: August 2021

Background

Bladder cancer (BLCA) is one of the most common urinary malignancies with poor prognosis. There is an unmet need to develop novel robust tools to predict prognosis and treatment efficacy for BLCA.

Methods

The hypoxia-related genes were collected from the Molecular Signatures Database. The TCGA-BLCA cohort was downloaded from the Cancer Genome Atlas and then was randomly divided into training and internal validation sets. Two external validation cohorts were gathered from Gene Expression Omnibus. Also, another independent validation cohort (Xiangya cohort) was collected from our hospital. The Cox regression model with the LASSO algorithm was applied to develop the hypoxia risk score. Then, we correlated the hypoxia risk score with the clinical outcomes, the tumor microenvironment (TME) immune characteristics, and the efficacy prediction for several treatments, which included cancer immunotherapy, chemotherapy, radiotherapy, and targeted therapies.

Results

Hypoxia risk score was an independent prognostic factor. A high-risk score indicated an inflamed TME based on the evidence that hypoxia risk score positively correlated with the activities of several cancer immunity cycles and the infiltration levels of many tumor-infiltrating immune cells, such as CD8 + T cells, Dendritic cells, and NK cells. Consistently, the hypoxia risk score was positively related to the expression of several immune checkpoints, such as PD-L1, PD-1, CTLA-4, and LAG-3, as well as the T cell inflamed score. Furthermore, the hypoxia risk score positively correlated with the enrichment scores of most immunotherapy-positive gene signatures. Therefore, patients with higher risk score may be more sensitive to cancer immunotherapy. Meanwhile, the hypoxia risk score was positively related to the sensitivities of several chemotherapeutic drugs, including Cisplatin, Docetaxel, Paclitaxel, Bleomycin, Camptothecin, and Vinblastine. Similarly, the enrichment scores for radiotherapy-predicted pathways and EGFR ligands were higher in the high-risk score group. Conversely, the enrichment scores of several immunosuppressive oncogenic pathways were significantly higher in the low-risk score group, such as the WNT-β-catenin network, PPARG network, and FGFR3 network.

Conclusions

We developed and validated a new hypoxia risk score, which could predict the clinical outcomes and the TME immune characteristics of BLCA. In general, the hypoxia risk score may aid in the precision medicine for BLCA.
Identifying Immune Cell Infiltration and Effective Diagnostic Biomarkers in Rheumatoid Arthritis by Bioinformatics Analysis
Authors: Zhou Sheng , Lu Hongcheng , Xiong Min
Published: August 2021

Background

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder characterized by inflammatory cell infiltration, leading to persistent synovitis and joint destruction. The pathogenesis of RA remains unclear. This study aims to explore the immune molecular mechanism of RA through bioinformatics analysis.

Methods

Five microarray datasets and a high throughput sequencing dataset were downloaded. CIBERSORT algorithm was performed to evaluate immune cell infiltration in synovial tissues between RA and healthy control (HC). Wilcoxon test and Least Absolute Shrinkage and Selection Operator (LASSO) regression were conducted to identify the significantly different infiltrates of immune cells. Differentially expressed genes (DEGs) were screened by “Batch correction” and “RobustRankAggreg” methods. Functional correlation of DEGs were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Candidate biomarkers were identified by cytoHubba of Cytoscape, and their diagnostic effectiveness was predicted by Receiver Operator Characteristic Curve (ROC) analysis. The association of the identified biomarkers with infiltrating immune cells was explored using Spearman’s rank correlation analysis in R software.

Results

Ten significantly different types of immune cells between RA and HC were identified. A total of 202 DEGs were obtained by intersection of DEGs screened by two methods. The function of DEGs were significantly associated with immune cells. Five hub genes (CXCR4, CCL5, CD8A, CD247, and GZMA) were screened by R package “UpSet”. CCL5+CXCR4 and GZMA+CD8A were verified to have the capability to diagnose RA and early RA with the most excellent specificity and sensitivity, respectively. The correlation between immune cells and biomarkers showed that CCL5 was positively correlated with M1 macrophages, CXCR4 was positively correlated with memory activated CD4+ T cells and follicular helper T (Tfh) cells, and GZMA was positively correlated with Tfh cells.

Conclusions

CCL5, CXCR4, GZMA, and CD8A can be used as diagnostic biomarker for RA. GZMA-Tfh cells, CCL5-M1 macrophages, and CXCR4- memory activated CD4+ T cells/Tfh cells may participate in the occurrence and development of RA, especially GZMA-Tfh cells for the early pathogenesis of RA.
Pathogenic Mechanisms of Vaccine-Induced Immune Thrombotic Thrombocytopenia in People Receiving Anti-COVID-19 Adenoviral-Based Vaccines: A Proposal
Authors: Azzarone Bruno , Veneziani Irene , Moretta Lorenzo , Maggi Enrico
Published: August 2021

VITT is a rare, life-threatening syndrome characterized by thrombotic symptoms in combination with thrombocytopenia, which may occur in individuals receiving the first administration of adenoviral non replicating vectors (AVV) anti Covid19 vaccines. Vaccine-induced immune thrombotic thrombocytopenia (VITT) is characterized by high levels of serum IgG that bind PF4/polyanion complexes, thus triggering platelet activation. Therefore, identification of the fine pathophysiological mechanism by which vaccine components trigger platelet activation is mandatory. Herein, we propose a multistep mechanism involving both the AVV and the neo-synthetized Spike protein. The former can: i) spread rapidly into blood stream, ii), promote the early production of high levels of IL-6, iii) interact with erythrocytes, platelets, mast cells and endothelia, iv) favor the presence of extracellular DNA at the site of injection, v) activate platelets and mast cells to release PF4 and heparin. Moreover, AVV infection of mast cells may trigger aberrant inflammatory and immune responses in people affected by the mast cell activation syndrome (MCAS). The pre-existence of natural antibodies binding PF4/heparin complexes may amplify platelet activation and thrombotic events. Finally, neosynthesized Covid 19 Spike protein interacting with its ACE2 receptor on endothelia, platelets and leucocyte may trigger further thrombotic events unleashing the WITT syndrome.
Transcriptome Analysis Reveals Impaired Fertility and Immunity Under Salinity Exposure in Juvenile Grass Carp
Authors: Zhang Jingjing , Wu Zhi , He Yujie , Li Xinhui , Li Jie
Published: August 2021

Grass carp (Ctenopharyngodon idellus) is one of the most economically important aquaculture species and is widely cultured in China. However, its wild populations in many rivers are increasingly declining, and seawater intrusion is one of the most important threats to their survival. However, the mechanisms underlying the decline due to salinity pressure are still unknown. Here, we performed a comparative transcriptome analysis of C. idellus larvae in response to salinity exposures; a total of 481 differentially expressed genes (DEGs) were identified. These DEGs were significantly enriched in eight Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, among which steroid biosynthesis was the most important one, with the highest enrichment score. The pathway plays an important role in the development of the testes and ovary. Interestingly, all DEGs in steroid biosynthesis showed a down regulation, indicating that salinity exposure may pose damage to the fertility of C. idellus. Furthermore, three immunity-associated pathways (cytokine–cytokine receptor interaction, Toll-like receptor signaling pathway, and NOD-like receptor signaling pathway) were also significantly enriched, suggesting impaired immunity and a high risk of disease infection under salinity exposure. Overall, damage to both fertility and immunity would decrease the number of offspring and increase the risk of death due to disease infection. Our results provide a potential molecular mechanism underlying the decline of wild C. idellus populations in the Pearl River.
How to Reduce the Transmission Risk of COVID-19 More Effectively in New York City: An Age-Structured Model Study
Authors: Li Miaolei , Zu Jian , Li Zongfang , Shen Mingwang , Li Yan , Ji Fanpu
Published: August 2021

Background: In face of the continuing worldwide COVID-19 epidemic, how to reduce the transmission risk of COVID-19 more effectively is still a major public health challenge that needs to be addressed urgently.

Objective: This study aimed to develop an age-structured compartment model to evaluate the impact of all diagnosed and all hospitalized on the epidemic trend of COVID-19, and explore innovative and effective releasing strategies for different age groups to prevent the second wave of COVID-19.

Methods: Based on three types of COVID-19 data in New York City (NYC), we calibrated the model and estimated the unknown parameters using the Markov Chain Monte Carlo (MCMC) method.

Results: Compared with the current practice in NYC, we estimated that if all infected people were diagnosed from March 26, April 5 to April 15, 2020, respectively, then the number of new infections on April 22 was reduced by 98.02, 93.88, and 74.08%. If all confirmed cases were hospitalized from March 26, April 5, and April 15, 2020, respectively, then as of June 7, 2020, the total number of deaths in NYC was reduced by 67.24, 63.43, and 51.79%. When only the 0–17 age group in NYC was released from June 8, if the contact rate in this age group remained below 61% of the pre-pandemic level, then a second wave of COVID-19 could be prevented in NYC. When both the 0–17 and 18–44 age groups in NYC were released from June 8, if the contact rates in these two age groups maintained below 36% of the pre-pandemic level, then a second wave of COVID-19 could be prevented in NYC.

Conclusions: If all infected people were diagnosed in time, the daily number of new infections could be significantly reduced in NYC. If all confirmed cases were hospitalized in time, the total number of deaths could be significantly reduced in NYC. Keeping a social distance and relaxing lockdown restrictions for people between the ages of 0 and 44 could not lead to a second wave of COVID-19 in NYC.
Macular Structure and Microvasculature Changes in AIDS-Related Cytomegalovirus Retinitis Using Optical Coherence Tomography Angiography
Authors: Du Kui-Fang , Huang Xiao-Jie , Chen Chao , Kong Wen-Jun , Xie Lian-Yong , Wei Wen-Bin
Published: August 2021

Background: Cytomegalovirus retinitis (CMVR) is a crucial blind-causing disease of AIDS-related ocular opportunistic infection. The CMVR lesions produced retinal necrosis. It is not entirely clear whether CMVR eyes without macular-involved necrotic lesions may have subtle macular damage. In this study, we conducted a cross-sectional study using optical coherence tomography angiography (OCTA) to evaluate macular microvasculature and structure in eyes with AIDS-related CMVR.

Methods: Acquired immune deficiency syndrome (AIDS)-related CMVR patients (active and inactive CMVR) and healthy controls treated in the Department of Ophthalmology, Beijing Youan Hospital, Capital Medical University between August 25, 2019, and October 18, 2019, were recruited. All OCTA parameters, including the foveal avascular zone (FAZ), retinal vessel density (VD), choroidal vascularity index (CVI), retinal thickness, and choroidal thickness, were compared between groups after the signal strength was corrected.

Results: Signal strength in the 3 × 3 and 6 × 6 mm scan patterns was significantly weaker in the inactive CMVR group than in the control group (both p < 0.001). After adjusting for signal strength, heterogeneity in the central fovea and parafoveal quadrants was present with a shift toward lower macular chorioretinal vasculature, decreased full choroidal thickness, and thicker retinal thickness in the active and inactive CMVR groups. The retinal nerve fiber layer (RNFL) and inner nuclear layer (INL) were significantly thicker in the active and inactive CMVR groups than in the control group (all p < 0.05). For photoreceptor-retinal pigment epithelium (PR-RPE) thickness, no significant differences were found in any quadrant between groups. Foveal avascular zone areas were not significantly different among the three groups (p = 0.053).

Conclusions: Subtle macular structure and microvasculature damage still existed in CMVR eyes without macular-involved necrotic lesions. The results of our study are helpful for a deep understanding of the damage caused by CMVR.
Enhanced Chitin Deacetylase Production Ability of Rhodococcus equi CGMCC14861 by Co-culture Fermentation With Staphylococcus sp. MC7
Authors: Ma Qinyuan , Gao Xiuzhen , Tu Linna , Han Qi , Zhang Xing , Guo Yabo , Yan Wenqin , Shen Yanbing , Wang Min
Published: August 2021

Graphical Abstract

GRAPHICAL ABSTRACT
Delivery Mode Affects Intestinal Microbial Composition and the Development of Intestinal Epithelial Cells
Authors: Lyu Linzheng , Zhou Xiaohong , Zhang Meng , Liu Li , Niu Haiyue , Zhang Jiliang , Chen Shiwei , Gong Pimin , Jiang Shilong , Pan Jiancun , Li Yuanyuan , Han Xue , Cheng Dayou , Zhang Lanwei
Published: August 2021

Background

The infant’s intestine contains diverse microbiota, which play an important role in an infant’s health.

Objective

This study aimed to analyze the different intestinal microbiota and their function in two delivery modes [vaginal delivery and cesarean section (C-section)] and to investigate the proprieties of bacteria associated with vaginal delivery on the development of intestinal epithelial cells in rat pups.

Materials and Methods

We evaluated the intestinal microbial diversity of the stool samples of 51 infants of subjects who underwent vaginal delivery and C-section by sequencing the V4 regions of the 16S rRNA gene and predicted the function of the microbiotas. The infant stool microbiota in the vaginal delivery group was associated with the digestive system and cell growth and death, whereas that of the C-section group was associated with membrane transport. Then, we isolated the strains based on function prediction.

Results

A total of 95 strains were isolated in the vaginal delivery group. Bifidobacterium bifidum FL-228.1 (FL-228.1) was screened and selected owing to its good surface hydrophobicity, bacterial survivability in the simulated gastrointestinal condition and adhesion ability to the IEC-6 cell line as well as owing to the development of intestinal epithelial cells. Furthermore, in vivo experiments revealed that FL-228.1 exhibited favorable effects on the development of intestinal epithelial cells in rat pups.

Conclusion

The results of this study indicate an apparent difference in the bacterial composition of the stool samples collected from infants of the two delivery modes. By analyzing and screening the bacteria in infant stool samples, we found that one strain, i.e., B bifidum FL-228.1, exhibited favorable effects on the development of intestinal epithelial cells.
Diversity and Biocontrol Potential of Culturable Endophytic Fungi in Cotton
Authors: Jin Lirong , Yang Long , Li Wenjing , Xu Dong , Yang Nina , Li Guoqing , Wan Peng
Published: August 2021

Healthy cotton samples were collected and 93 endophytic fungal strains were isolated: 23 strains from the roots and 70 strains from the stems. Morphological characterization and ITS sequence analysis were used for the identification of these isolates. The results showed that the 93 strains including 20 species were highly diverse in terms of their taxonomy. Simpson’s and Shannon’s diversity indices were 0.915 and 3.848, respectively. Fusarium and Alternaria were the two dominant genera, constituting 19.4% of the total strains. Then, 72 spore-producing strains were tested for the suppression of cotton Verticillium wilt (CVW) caused by Verticillium dahliae in a greenhouse. Five strains exhibited effective suppression of CVW with average efficacy values higher than 50%. One of the effective strains, namely, Fusarium proliferatum 10R-7, was selected for the investigation of the role of fusaric acid, a secondary metabolite of strain 10R-7, in the suppression of V. dahliae and CVW. The results showed that F. proliferatum 10R-7 could produce fusaric acid, and this metabolite exhibited 100% inhibition of mycelial growth of V. dahliae at concentrations higher than 20 μg/ml. However, fusaric acid at 2.5 to 80 μg/ml was not effective in the suppression of CVW, compared with the control treatment with V. dahliae alone. F. proliferatum 10R-7 was labeled with green fluorescent protein (GFP), and the GFP-tagged strain was found to be able to colonize inside the taproots of cotton, suggesting that F. proliferatum 10R-7 is a true endophyte of cotton and endophytic colonization may play a role in the suppression of infection of cotton by V. dahliae.
Production of Four 15N-Labelled Cobalamins via Biosynthesis Using Propionibacterium freudenreichii
Authors: Wang Mengle , Asam Stefan , Chen Jianqi , Ehrmann Matthias , Rychlik Michael
Published: August 2021

Cobalamins (vitamin B12) are required by humans for their essential roles as enzyme cofactors in diverse metabolic processes. The four most common cobalamin vitamers are hydroxocobalamin (OHCbl), adenosylcobalamin (AdoCbl), methylcobalamin (MeCbl), and cyanocobalamin (CNCbl). Humans are not able to synthesise cobalamins de novo and thus must acquire them from external sources. Therefore, a reliable and robust analytical method to determine the cobalamins in dietary sources is highly required. For such a purpose, stable isotope dilution assays (SIDAs) with LC-MS/MS are most suited due to their superior sensitivity, specificity, and ability to compensate for matrix effects and analyte loss during sample work-up. However, a critical bottleneck for developing a SIDA method for cobalamins is the availability of stable isotope-labelled internal standards. In the present study, we harnessed the potential of Propionibacterium (P.) freudenreichii for the biosynthesis of 15N-labelled cobalamins. First, we developed a chemically defined medium (CDM) containing ammonium sulphate as a single nitrogen source except three essential vitamins that supported long-term stable growth of P. freudenreichii throughout continuous transfers. The CDM was further optimised for cobalamin production under different incubation schemes. With the optimised CDM and incubation scheme, fully 15N-labelled cobalamins were obtained in P. freudenreichii with a final yield of 312 ± 29 μg/L and 635 ± 102 μg/L, respectively, for [15N]-OHCbl and [15N]-AdoCbl. Additionally, an optimised incubation process under anaerobic conditions was successfully employed to produce specifically labelled [15N, 14N2]-cobalamins, with a yield of 96 ± 18 μg/L and 990 ± 210 μg/L, respectively, for [15N, 14N2]-OHCbl and [15N, 14N2]-AdoCbl. The labelled substances were isolated and purified by solid phase extraction and semi-preparative HPLC. Chemical modifications were carried out to produce [15N]-CNCbl and [15N]-MeCbl. Eventually, 15N-labelled compounds were obtained for the four cobalamin vitamers in high chromatographic and isotopic purity with desired 15N-enrichment and labelling patterns, which are perfectly suited for future use in SIDAs or other applications that require isotopologues.
Transcriptional Analysis of Infection With Early or Late Isolates From the 2013–2016 West Africa Ebola Virus Epidemic Does Not Suggest Attenuated Pathogenicity as a Result of Genetic Variation
Authors: Maroney Kevin J. , Pinski Amanda N. , Marzi Andrea , Messaoudi Ilhem
Published: August 2021

The 2013–2016 West Africa Ebola virus (EBOV) epidemic caused by the EBOV-Makona isolate is the largest and longest recorded to date. It incurred over 28,000 infections and ∼11,000 deaths. Early in this epidemic, several mutations in viral glycoprotein (A82V), nucleoprotein (R111C), and polymerase L (D759G) emerged and stabilized. In vitro studies of these new EBOV-Makona isolates showed enhanced fitness and viral replication capacity. However, in vivo studies in mice and rhesus macaques did not provide any evidence of enhanced viral fitness or shedding. Infection with late isolates carrying or early isolates lacking (early) these mutations resulted in uniformly lethal disease in nonhuman primates (NHPs), albeit with slightly delayed kinetics with late isolates. The recent report of a possible reemergence of EBOV from a persistent infection in a survivor of the epidemic highlights the urgency for understanding the impact of genetic variation on EBOV pathogenesis. However, potential molecular differences in host responses remain unknown. To address this gap in knowledge, we conducted the first comparative analysis of the host responses to lethal infection with EBOV-Mayinga and EBOV-Makona isolates using bivariate, longitudinal, regression, and discrimination transcriptomic analyses. Our analysis shows a conserved core of differentially expressed genes (DEGs) involved in antiviral defense, immune cell activation, and inflammatory processes in response to EBOV-Makona and EBOV-Mayinga infections. Additionally, EBOV-Makona and EBOV-Mayinga infections could be discriminated based on the expression pattern of a small subset of genes. Transcriptional responses to EBOV-Makona isolates that emerged later during the epidemic, specifically those from Mali and Liberia, lacked signatures of profound lymphopenia and excessive inflammation seen following infection with EBOV-Mayinga and early EBOV-Makona isolate C07. Overall, these findings provide novel insight into the mechanisms underlying the lower case fatality rate (CFR) observed with EBOV-Makona compared to EBOV-Mayinga.
Prostaglandin E2 Dilates Intracerebral Arterioles When Applied to Capillaries: Implications for Small Vessel Diseases
Authors: Rosehart Amanda C. , Longden Thomas A. , Weir Nick , Fontaine Jackson T. , Joutel Anne , Dabertrand Fabrice
Published: August 2021

Prostaglandin E2 (PGE2) has been widely proposed to mediate neurovascular coupling by dilating brain parenchymal arterioles through activation of prostanoid EP4 receptors. However, our previous report that direct application of PGE2 induces an EP1-mediated constriction strongly argues against its direct action on arterioles during neurovascular coupling, the mechanisms sustaining functional hyperemia. Recent advances have highlighted the role of capillaries in sensing neuronal activity and propagating vasodilatory signals to the upstream penetrating parenchymal arteriole. Here, we examined the effect of capillary stimulation with PGE2 on upstream arteriolar diameter using an ex vivo capillary-parenchymal arteriole preparation and in vivo cerebral blood flow measurements with two-photon laser-scanning microscopy. We found that PGE2 caused upstream arteriolar dilation when applied onto capillaries with an EC50 of 70 nM. The response was inhibited by EP1 receptor antagonist and was greatly reduced, but not abolished, by blocking the strong inward-rectifier K+ channel. We further observed a blunted dilatory response to capillary stimulation with PGE2 in a genetic mouse model of cerebral small vessel disease with impaired functional hyperemia. This evidence casts previous findings in a different light, indicating that capillaries are the locus of PGE2 action to induce upstream arteriolar dilation in the control of brain blood flow, thereby providing a paradigm-shifting view that nonetheless remains coherent with the broad contours of a substantial body of existing literature.
Pharmacological Interventions for REM Sleep Behavior Disorder in Parkinson's Disease: A Systematic Review
Authors: Yan Junqiang , Liu Anran , Huang Jiarui , Wu Jiannan , Shen Ruile , Ma Hongxia , Yang Jianxue
Published: August 2021

To review the therapeutic effects of drugs on REM sleep behavior disorder (RBD) in Parkinson's disease (PD) by searching the MEDLINE/PubMed, Embase, Cochrane, and CBM databases. According to the inclusion and exclusion criteria, studies were included after excluding duplicate data. We evaluated the safety and efficacy of pharmacological intervention to improve RBD in patients with Parkinson's disease (PD-RBD). This systematic review mainly describes the drugs that can be used to treat PD-RBD patients. The results have shown that melatonin can be used as the first-line drug for PD-RBD, and clonazepam provides significant improvement on PD-RBD, androtigotine can be used as an alternative drug. However, further large-scale clinical trial studies are still needed to provide the best guidelines for the pharmacological treatment of PD-RBD.
Spiking Autoencoders With Temporal Coding
Authors: Comşa Iulia-Maria , Versari Luca , Fischbacher Thomas , Alakuijala Jyrki
Published: August 2021

Spiking neural networks with temporal coding schemes process information based on the relative timing of neuronal spikes. In supervised learning tasks, temporal coding allows learning through backpropagation with exact derivatives, and achieves accuracies on par with conventional artificial neural networks. Here we introduce spiking autoencoders with temporal coding and pulses, trained using backpropagation to store and reconstruct images with high fidelity from compact representations. We show that spiking autoencoders with a single layer are able to effectively represent and reconstruct images from the neuromorphically-encoded MNIST and FMNIST datasets. We explore the effect of different spike time target latencies, data noise levels and embedding sizes, as well as the classification performance from the embeddings. The spiking autoencoders achieve results similar to or better than conventional non-spiking autoencoders. We find that inhibition is essential in the functioning of the spiking autoencoders, particularly when the input needs to be memorised for a longer time before the expected output spike times. To reconstruct images with a high target latency, the network learns to accumulate negative evidence and to use the pulses as excitatory triggers for producing the output spikes at the required times. Our results highlight the potential of spiking autoencoders as building blocks for more complex biologically-inspired architectures. We also provide open-source code for the model.