bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the Impact of Culture: A Systematic Analysis of Culture-Based Interventions and Evaluations
Authors: Austin Eric , Ward Nic , Otto Jay , Green Kelly , Watson Holly
Published: July 2022

Over the last 20 years, transportation agencies have added culture-based approaches to the existing education, engineering, and enforcement (3E) strategies being used as a means of reducing traffic related injuries and fatalities. Despite this increased interest, there have been comparatively few evaluations of these interventions. At the same time, many other organizational types have adopted culture-based strategies either to improve safety or to enhance other elements of organizational performance. In aggregate, the evaluations of culture-focused interventions across a range of settings offer an untapped body of information about the models of culture being leveraged to affect change, the intervention strategies used to impact culture, the impacts of these strategies, and more. The research presented here used a systematic analysis of published, peer-reviewed evaluations of culture-based interventions designed to enhance traffic safety, safe workplaces, and effective practices more broadly, in order to more comprehensively understand the current state and impacts of culture-based theory and practices. This study seeks to build a clearer picture of the presence and robustness of current models of culture being utilized, as well as what evaluation strategies and designs are being used to assess culture-based initiatives, and further, what the robustness of the existing models and evaluation designs reveal about the efficacy of the original, culture-based interventions. Lastly, this analysis includes a preliminary examination of links between culture-based initiatives and systems theory/thinking, in an effort to identify conceptual ties between and/or empirical evidence supporting a relationship between the “Safe System” approach and traffic safety culture or other culture-based efforts. It is hoped that with a clearer understanding of the status of the field, it will be possible to make further progress in crafting, assessing, and refining theoretically robust and empirically grounded efforts to advance the efficacy of traffic safety culture and safe systems approaches.
A Pan-Cancer Analysis of the Oncogenic Role of BCL7B: A Potential Biomarker for Prognosis and Immunotherapy
Authors: Yang Dinglong , Li Hetong , Chen Yujing , Li Chunjiang , Ren Weiping , Huang Yongbo
Published: July 2022

Background: Previous studies have partly explored the role of B-cell CLL/lymphoma 7 protein family member B (BCL7B) in tumorigenesis and development. However, the prognosis and immunoregulatory value of BCL7B in pan-cancer patients remains unclear.

Methods: Through The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, the distinct expression of BCL7B gene in 33 tumors and adjacent normal tissues was analyzed. The Kaplan–Meier method (univariate Cox regression analysis and Kaplan–Meier curve) was used to identify the cancer types whose BCL7B gene expression was related to prognosis. The receiver operating characteristic (ROC) curve was used to elucidate the diagnosis value of BCL7B gene. Spearman’s rank correlation coefficient was used to explore the relationship between BCL7B gene expression and immune cell infiltration, immune checkpoints, DNA methylation, DNA repair genes, immune-activating genes, immune-suppressing genes, immune subtypes, tumor mutation burden (TMB), and microsatellite instability (MSI). The Wilcoxon rank sum test and Kruskal–Wallis test were used to compare the expression of BCL7B gene in tumor tissues with different clinicopathological features. Gene set enrichment analysis (GSEA) was conducted to identify the tumor-related pathways in pan-cancer. The Human Protein Atlas (HPA) database was used to verify the BCL7B gene expression at the protein level.

Results: High expression of BCL7B was associated with an inferior prognosis in glioblastoma multiforme (GBM), glioma (GBMLGG), kidney chromophobe (KICH), brain lower grade glioma (LGG), oral squamous cell carcinoma (OSCC), rectum adenocarcinoma (READ), and uveal melanoma (UVM). Low expression of BCL7B was associated with a poor prognosis in kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), skin cutaneous melanoma (SKCM), thyroid carcinoma (THCA), and sarcoma (SARC). The BCL7B gene expression had varying degrees of correlation with 24 immune cell subsets in 37 tumor environments such as adrenocortical carcinoma (ACC) and bladder urothelial carcinoma (BCLA). Spearman’s rank correlation coefficient showed that BCL7B gene expression had different degrees of correlation with 47 immune checkpoints, 46 immune-activating genes, 24 immune-suppressing genes, 5 DNA repair genes, and DNA methylation, TMB, and MSI in 39 tumors. GSEA suggested that BCL7B was notably associated with cancer-related and immune-related pathways.

Conclusion: In summary, BCL7B gene has a high diagnostic and prognostic value in pan-cancer and is related to the infiltration of 24 immune cell subsets in pan-cancer.
Identification and Verification of Potential Biomarkers in Gastric Cancer By Integrated Bioinformatic Analysis
Authors: Sun Chenyu , Chen Yue , Kim Na Hyun , Lowe Scott , Ma Shaodi , Zhou Zhen , Bentley Rachel , Chen Yi-Sheng , Tuason Margarita Whitaker , Gu Wenchao , Bhan Chandur , Tuason John Pocholo Whitaker , Thapa Pratikshya , Cheng Ce , Zhou Qin , Zhu Yanzhe
Published: July 2022

Background: Gastric cancer (GC) is a common cancer with high mortality. This study aimed to identify its differentially expressed genes (DEGs) using bioinformatics methods.

Methods: DEGs were screened from four GEO (Gene Expression Omnibus) gene expression profiles. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. A protein–protein interaction (PPI) network was constructed. Expression and prognosis were assessed. Meta-analysis was conducted to further validate prognosis. The receiver operating characteristic curve (ROC) was analyzed to identify diagnostic markers, and a nomogram was developed. Exploration of drugs and immune cell infiltration analysis were conducted.

Results: Nine up-regulated and three down-regulated hub genes were identified, with close relations to gastric functions, extracellular activities, and structures. Overexpressed Collagen Type VIII Alpha 1 Chain (COL8A1), Collagen Type X Alpha 1 Chain (COL10A1), Collagen Triple Helix Repeat Containing 1 (CTHRC1), and Fibroblast Activation Protein (FAP) correlated with poor prognosis. The area under the curve (AUC) of ADAM Metallopeptidase With Thrombospondin Type 1 Motif 2 (ADAMTS2), COL10A1, Collagen Type XI Alpha 1 Chain (COL11A1), and CTHRC1 was >0.9. A nomogram model based on CTHRC1 was developed. Infiltration of macrophages, neutrophils, and dendritic cells positively correlated with COL8A1, COL10A1, CTHRC1, and FAP. Meta-analysis confirmed poor prognosis of overexpressed CTHRC1.

Conclusion: ADAMTS2, COL10A1, COL11A1, and CTHRC1 have diagnostic values in GC. COL8A1, COL10A1, CTHRC1, and FAP correlated with worse prognosis, showing prognostic and therapeutic values. The immune cell infiltration needs further investigations.
Selecting Representative Samples From Complex Biological Datasets Using K-Medoids Clustering
Authors: Li Lei , Lan Linda Yu-Ling , Huang Lei , Ye Congting , Andrade Jorge , Wilson Patrick C.
Published: July 2022

Rapid growth of single-cell sequencing techniques enables researchers to investigate almost millions of cells with diverse properties in a single experiment. Meanwhile, it also presents great challenges for selecting representative samples from massive single-cell populations for further experimental characterization, which requires a robust and compact sampling with balancing diverse properties of different priority levels. The conventional sampling methods fail to generate representative and generalizable subsets from a massive single-cell population or more complicated ensembles. Here, we present a toolkit called Cookie which can efficiently select out the most representative samples from a massive single-cell population with diverse properties. This method quantifies the relationships/similarities among samples using their Manhattan distances by vectorizing all given properties and then determines an appropriate sample size by evaluating the coverage of key properties from multiple candidate sizes, following by a k-medoids clustering to group samples into several clusters and selects centers from each cluster as the most representatives. Comparison of Cookie with conventional sampling methods using a single-cell atlas dataset, epidemiology surveillance data, and a simulated dataset shows the high efficacy, efficiency, and flexibly of Cookie. The Cookie toolkit is implemented in R and is freely available at https://wilsonimmunologylab.github.io/Cookie/.
Machine Learning Approaches to TCR Repertoire Analysis
Authors: Katayama Yotaro , Yokota Ryo , Akiyama Taishin , Kobayashi Tetsuya J.
Published: July 2022

Sparked by the development of genome sequencing technology, the quantity and quality of data handled in immunological research have been changing dramatically. Various data and database platforms are now driving the rapid progress of machine learning for immunological data analysis. Of various topics in immunology, T cell receptor repertoire analysis is one of the most important targets of machine learning for assessing the state and abnormalities of immune systems. In this paper, we review recent repertoire analysis methods based on machine learning and deep learning and discuss their prospects.
Specific CD4+ T Cell Responses to Ancestral SARS-CoV-2 in Children Increase With Age and Show Cross-Reactivity to Beta Variant
Authors: Paul Kevin , Sibbertsen Freya , Weiskopf Daniela , Lütgehetmann Marc , Barroso Madalena , Danecka Marta K. , Glau Laura , Hecher Laura , Hermann Katharina , Kohl Aloisa , Oh Jun , Schulze zur Wiesch Julian , Sette Alessandro , Tolosa Eva , Vettorazzi Eik , Woidy Mathias , Zapf Antonia , Zazara Dimitra E. , Mir Thomas S. , Muntau Ania C. , Gersting Søren W. , Dunay Gabor A.
Published: July 2022

SARS-CoV-2 is still a major burden for global health despite effective vaccines. With the reduction of social distancing measures, infection rates are increasing in children, while data on the pediatric immune response to SARS-CoV-2 infection is still lacking. Although the typical disease course in children has been mild, emerging variants may present new challenges in this age group. Peripheral blood mononuclear cells (PBMC) from 51 convalescent children, 24 seronegative siblings from early 2020, and 51 unexposed controls were stimulated with SARS-CoV-2-derived peptide MegaPools from the ancestral and beta variants. Flow cytometric determination of activation-induced markers and secreted cytokines were used to quantify the CD4+ T cell response. The average time after infection was over 80 days. CD4+ T cell responses were detected in 61% of convalescent children and were markedly reduced in preschool children. Cross-reactive T cells for the SARS-CoV-2 beta variant were identified in 45% of cases after infection with an ancestral SARS-CoV-2 variant. The CD4+ T cell response was accompanied most predominantly by IFN-γ and Granzyme B secretion. An antiviral CD4+ T cell response was present in children after ancestral SARS-CoV-2 infection, which was reduced in the youngest age group. We detected significant cross-reactivity of CD4+ T cell responses to the more recently evolved immune-escaping beta variant. Our findings have epidemiologic relevance for children regarding novel viral variants of concern and vaccination efforts.
A Landscape Study on COVID-19 Immunity at the Single-Cell Level
Authors: Wei Rongguo , Qin Zheng , Huang Qi , Liu Lulu , Cheng Fang , Meng Songdong , Wang Lin
Published: July 2022

Since 2019, the coronavirus (COVID-19) has outbroken continuously, spreading internationally and threatening the public health. However, it was unknown how the disorder at the single-cell level was associated with the pathogenesis of COVID-19. This study presented the disorders of macrophages, epithelial cells, CD8+ T cells, and natural killer (NK) cells at the single-cell level in the courses of COVID-19 and analyzed the immune response to cytokine storm. Compared with the healthy group, patients with COVID-19 had higher proportions of macrophages and lower proportions of T and NK cells, especially proportions of macrophages and epithelial cells with an increase during patients’ conditions from mild to severe. This study suggested that there were high levels of pro-inflammatory and chemokine expressions in cells of COVID-19 and analyzed cell subsets to explore its changes and pathways. It was worth noting that several subsets of macrophages, epithelial cells, CD8 T cells, and NK cells were involved in inflammation pathways, including interleukin-17 (IL-17) signaling pathway and tumor necrosis factor (TNF) signaling pathway. Moreover, the pathways interacting COVID-19 and cytokine receptor with each other were remarkably enriched. In addition, these cell subsets played important roles in inflammation, and their abnormal functions may cause COVID-19. In conclusion, this study provided an immune outlook for COVID-19 at the single-cell level and revealed different pathways in immune response of COVID-19 single cells.
Divide and Conquer: Phenotypic and Temporal Heterogeneity Within CD8+ T Cell Responses
Authors: Richard Arianne C.
Published: July 2022

The advent of technologies that can characterize the phenotypes, functions and fates of individual cells has revealed extensive and often unexpected levels of diversity between cells that are nominally of the same subset. CD8+ T cells, also known as cytotoxic T lymphocytes (CTLs), are no exception. Investigations of individual CD8+ T cells both in vitro and in vivo have highlighted the heterogeneity of cellular responses at the levels of activation, differentiation and function. This review takes a broad perspective on the topic of heterogeneity, outlining different forms of variation that arise during a CD8+ T cell response. Specific attention is paid to the impact of T cell receptor (TCR) stimulation strength on heterogeneity. In particular, this review endeavors to highlight connections between variation at different cellular stages, presenting known mechanisms and key open questions about how variation between cells can arise and propagate.
β-Glucan: Mode of Action and Its Uses in Fish Immunomodulation
Authors: Hadiuzzaman Md , Moniruzzaman Mohammad , Shahjahan Md , Bai Sungchul C. , Min Taesun , Hossain Zakir
Published: July 2022

β-glucan is considered as an effective immunostimulant because of its binding capacity to different receptors on leukocytes leading to the stimulation of immune responses including bactericidal activity, cytokine productivity, and survival fit ability at cellular levels. In response to immune cell surface receptors, β-glucan stimulates to release cytokines and chemokines. It has been found that these signaling proteins eventually stimulate the immunocompetent cells in fish such as monocytes, macrophages, and neutrophils for killing pathogens by phagocytosis, oxidative burst, and cytotoxic killing activities. They also procreate immunological memories and specific antibodies through activation of T and B lymphocytes. Researchers have proved that β-glucan can modulate some important biochemical (serum hemoglobin, serum protein, and total hemocyte count) and immunological (lysozyme activity, phagocytic activity, oxidative burst activity, and phenoloxidase activity) properties providing more competent immune profile for treating fish and aquatic organisms. β-glucan-supplemented fish showed limited sensitivity of genes involved in acute inflammatory reactions. Findings have shown that β-glucan exerts a positive impact on fish and aquatic organisms’ immunity, enhancing their disease resistance by increasing functional and decreasing deleterious responses. This review focuses on the basic bump of β-glucan on fish and shellfish immunity and recent information on the uses of β-glucan in progressive aquaculture.
Tracing Land-Based Microplastic Sources in Coastal Waters of Zhanjiang Bay, China: Spatiotemporal Pattern, Composition, and Flux
Authors: Wang Shujia , Jian Qiying , Zhang Peng , Zhang Jibiao , Zhao Lirong , Liu Dan , Kang Xinhuang
Published: July 2022

Estuaries and sewage outlets are key pathways for the transport of microplastics (MPs) from land to coastal waters. In this study, the spatiotemporal pattern, composition, and flux of MPs transported from land to Zhanjiang Bay (ZJB) in the South China Sea were investigated. The results showed that the overall mean MP abundance (± standard deviation) was 17.99 ± 9.72 items/L, with the highest in the normal season, followed by the dry and wet seasons. Fibers were the most dominant shape in these samples, blue was the most common color, and most MPs ranged between 100 and 330 μm. The MP diversity was higher in the wet and normal seasons than in the dry season. The highest seasonal flux of MPs was observed during the wet season, accounting for 79.68%, with the largest contribution from the Suixi River. There was a significant positive relationship between the annual MP flux and river discharge (R² = 0.95, p< 0.001). Hydrological processes, human behavior, and weather conditions were key factors that contributed toward the spatiotemporal variation of MPs. Overall, the aim of this study was to provide baseline information on MP pollution in ZJB to help formulate control strategies for improving regional water quality and mitigating its pollution. In the future, this study can be used to assess the role of river basins and sewage outlets in transporting MPs to the estuaries and ocean.
Embryo Development and Effects of Temperature, Salinity, and Light Intensity on Egg Hatching of Calanoid Copepod Bestiolina amoyensis (Calanoida: Paracalanidae)
Authors: Wang Shuhong , Wang Lin , Wang Yuyue , Chen Yun , Chen Jinmin , Chen Nan
Published: July 2022

Bestiolina amoyensis distributes in subtropical inshore waters across the Pacific Ocean, with a relatively long reproductive lifespan and high intrinsic population increase rate compared with other small paracalanid species, which makes it a good candidate to develop culture techniques for hatchery larval rearing. However, the reproductive biology of this subtropical broadcast spawning species is still largely unknown. The present investigation provides the first published data on the embryo development and effects of different light intensities (0, 500, and 1,000 lx), temperatures (16°C, 18°C, 20°C, 22°C, 24°C, 26°C, 28°C, 30°C, 32°C, and 34°C), and salinities (22, 24, 26, 28, 30, 32, and 34 psu) on hatching success rates of B. amoyensis. The same batch of eggs were collected from gravid females to observe their embryonic development and incubated under designed light intensities, temperatures, and salinities. Results showed that the whole embryonic development of B. amoyensis lasted, on average, 6 h and 40 min at 26°C, and egg hatching time of B. amoyensis shortened exponentially with the increasing temperature. The highest egg hatching rate (100%) was recorded from the 0-lx treatment, indicating that the dark condition was favorable for the egg incubation of B. amoyensis. The optimum temperature and salinity range for the hatching success of B. amoyensis was 22°C–30°C (above 94%) and 22–34 psu salinity (above 88%), respectively, indicating that B. amoyensis had wide adaptability to temperature and salinity. Light and too low or high temperature leads to abnormal embryonic development and malformed nauplii. The relatively wide adaptability to temperature and salinity and fast embryo development also suggests that B. amoyensis was a good candidate as live feed for hatchery larval rearing.
Establishment of the reproducible branch retinal artery occlusion mouse model and intravital longitudinal imaging of the retinal CX3CR1-GFP+ cells after spontaneous arterial recanalization
Authors: Jeon Jehwi , Kim Sang-Hoon , Kong Eunji , Kim Soo Jin , Yang Jee Myung , Lee Joo Yong , Lee Junyeop , Kim You-Me , Kim Pilhan
Published: July 2022

Animal models of retinal artery occlusion (RAO) have been widely used in many studies. However, most of these studies prefer using a central retinal artery occlusion (CRAO) which is a typical global ischemia model of the retina, due to the technical limitation of producing single vessel targeted modeling with real-time imaging. A focal ischemia model, such as branch retinal artery occlusion (BRAO), is also needed for explaining interactions, including the immunological reaction between the ischemic retina and adjacent healthy retina. Accordingly, a relevant model for clinical RAO patients has been demanded to understand the pathophysiology of the RAO disease. Herein, we establish a convenient BRAO mouse model to research the focal reaction of the retina. As a photo-thrombotic agent, Rose bengal was intravenously injected into 7 week-old transgenic mice (CX3CR1-GFP) for making embolism occlusion, which causes pathology similarly to clinical cases. In an optimized condition, a 561 nm laser (13.1 mw) was projected to a targeted vessel to induce photo-thrombosis for 27 s by custom-built retinal confocal microscopy. Compared to previous BRAO models, the procedures of thrombosis generation were naturally and minimal invasively generated with real-time retinal imaging. In addition, by utilizing the self-remission characteristics of Rose bengal thrombus, a reflow of the BRAO with immunological reactions of the CX3CR1-GFP+ inflammatory cells such as the retinal microglia and monocytes was monitored and analyzed. In this models, reperfusion began on day 3 after modeling. Simultaneously, the activation of CX3CR1-GFP+ inflammatory cells, including the increase of activation marker and morphologic change, was confirmed by immunohistochemical (IHC) staining and quantitative real-time PCR. CD86 and Nox2 were prominently expressed on day 3 after the modeling. At day 7, blood flow was almost restored in the large vessels. CX3CR1-GFP+ populations in both superficial and deep layers of the retina also increased around even in the BRAO peri-ischemic area. In summary, this study successfully establishes a reproducible BRAO modeling method with convenient capabilities of easily controllable time points and selection of a specific single vessel. It can be a useful tool to analyze the behavior of inflammatory cell after spontaneous arterial recanalization in BRAO and further investigate the pathophysiology of BRAO.
A systematic review of multidomain and lifestyle interventions to support the intrinsic capacity of the older population
Authors: Bevilacqua Roberta , Soraci Luca , Stara Vera , Riccardi Giovanni Renato , Corsonello Andrea , Pelliccioni Giuseppe , Lattanzio Fabrizia , Casaccia Sara , Möller Johanna , Wieching Rainer , Ogawa Toshimi , Watanabe Suichiro , Kokobun Keisuke , Kondo Izumi , Takano Eiko , Maranesi Elvira
Published: July 2022

Introduction

The focus on intrinsic capacity (IC) could help clinicians to design interventions to improve the health of the older population. This review aims to map the current state of the art in the field of multi-domain interventions based on the IC framework, to allow health professionals in identifying personalized clinical interventions, oriented to empower the older people with a holistic and positive approach.

Methods

A systematic review of the literature was conducted in July 2021 analyzing manuscripts and articles of the last 10.5 years from PubMed, Scopus, Embase, Google Scholar and Elsevier databases. A total of 12 papers were included.

Results

The majority of successful interventions are based on a goal setting approach where the older people are involved in the definition of the strategy to follow to remain active and independent. None of the study have used the IC as a framework to design a clinical intervention.

Conclusion

To the best of our knowledge, no other reviews are reported in the literature regarding the IC. Our study offers several research directions, which may take the existing debates to the next level.
Central Metabolism and Growth Rate Impacts on Hydrogen and Carbon Isotope Fractionation During Amino Acid Synthesis in E. coli
Authors: Smith Derek A. , Nakamoto Bobby James , Suess Melanie K. , Fogel Marilyn L.
Published: July 2022

Compound specific stable isotope analysis (CSIA) of amino acids from bacterial biomass is a newly emerging powerful tool for exploring central carbon metabolism pathways and fluxes. By comparing isotopic values and fractionations relative to water and growth substrate, the impact of variable flow path for metabolites through different central metabolic pathways, perturbations of these paths, and their resultant consequences on intracellular pools and resultant biomass may be elucidated. Here, we explore the effects that central carbon metabolism and growth rate can have on stable hydrogen (δ2H) and carbon (δ13C) compound specific isotopic values of amino acids, and whether diagnostic isotopic fingerprints are revealed by these paired analyses. We measured δ2H and δ13C in amino acids in the wild type Escherichia coli (MG1655) across a range of growth rates in chemostat cultures to address the unknown isotopic consequences as metabolic fluxes are shuffled between catabolic and anabolic metabolisms. Additionally, two E. coli knockout mutants, one with deficiency in glycolysis –pgi (LC1888) and another inhibiting the oxidative pentose phosphate pathway (OPPP) –zwf (LC1889), were grown on glucose and used as a comparison against the wild type E. coli (MG1655) to address the isotopic changes of amino acids produced in these perturbed metabolic pathways. Amino acid δ2H values, which collectively vary in composition by more than 400‰, are altered along with δ13C values demonstrating fundamental shifts in central metabolic pathways and/or fluxes. Within our linear discriminant analysis with a simple model organism to examine potential amino acid fingerprinting, our knockout strains and variable growth rate samples plot across a wider array of organism classification than merely within the boundaries of other bacterial data.
The Molecular Epidemiological and Immunological Characteristics of HIV-1 CRF01_AE/B Recombinants in Nanjing, China
Authors: Ge You , Liu Yangyang , Fu Gengfeng , Lu Jing , Li Xiaoshan , Du Guoping , Fei Gaoqiang , Wang Zemin , Li Han , Li Wei , Wei Pingmin
Published: July 2022

Human immunodeficiency virus-type 1 (HIV-1) CRF01_AE/B recombinants are newly emerging strains that are spreading rapidly in Southern and Eastern China. This study aimed to elucidate the molecular epidemiological characteristics of HIV-1 CRF01_AE/B recombinants in Nanjing and to explore the impact of these novel strains on the immunological status. A total of 1,013 blood samples from newly diagnosed HIV-1-infected patients were collected in Nanjing from 2015 to 2019, among which 958 partial Pol sequences were sequenced successfully. We depicted the molecular epidemiological characteristics of CRF01_AE/B recombinants by the molecular evolutionary analysis, Bayesian system evolution analysis, and transmission network analysis. The generalized additive mixed model was applied to evaluate the CD4+ T-cell count change of CRF01_AE/B recombinants. The Kaplan–Meier analysis was performed to assess the time from combined antiretroviral therapy (cART) initiation to immune reconstruction. We have identified 102 CRF01_AE/B recombinants (102/958, 10.65%) in Nanjing, including CRF67_01B (45/102, 44.12%), CRF68_01B (35/102, 34.31%), and CRF55_01B (22/102, 12.57%). According to the Bayesian phylogenetic inference, CRF55_01B had a rapid decline stage during 2017–2019, while CRF67_01B and CRF68_01B have experienced a fast growth phase during 2014–2015 and then remained stable. We have constructed 83 transmission networks, in which three larger clusters were composed of CRF67_01B and CRF68_01B. CRF01_AE/B recombinants manifested a faster decrease rate of CD4+ T-cell count than CRF_07BC but similar to CRF01_AE. The probability of achieving immune reconstruction in CRF01_AE/B recombinants was lower than CRF07_BC in the subgroup of baseline CD4+ T-cell count at cART initiation <300 cells/μl. In summary, CRF67_01B and CRF68_01B were the major strains of CRF01_AE/B recombinants in Nanjing, which have formed large transmission clusters between Nanjing and other provinces. CRF01_AE/B recombinants might be associated with rapid disease progression and poor immune reconstruction. The continuous epidemiological monitoring of CRF01_AE/B recombinants should be highly emphasized.
Land use alters diazotroph community structure by regulating bacterivores in Mollisols in Northeast China
Authors: Zhang Zhiming , Han Xiaozeng , Pan Fengjuan , Liu Hang , Yan Jun , Zou Wenxiu , McLaughlin Neil B. , Hao Xiangxiang
Published: July 2022

Changes in land use can generate environmental pressures that influence soil biodiversity, and numerous studies have examined the influences of land use on the soil microbial communities. However, little is known about the effects of land use on ecological interactions of soil microbes and their predators. Diazotrophs are key soil microbes that play important functional roles in fixing atmospheric nitrogen. In this study, we investigated the co-association of diazotroph community members and patterns of diazotroph and bacterivore networks under different long-term land uses including cropland, grassland, and bare land. Diazotroph community was characterized by high-throughput sequencing. The results indicated that land use type influenced the dominant genera of diazotrophs and shaped the occurrence of specific indicator diazotroph taxa. Co-existing pattern analysis of diazotrophs and bacterivores indicated that grassland converted from cropland increased the complexity of diazotroph and bacterivore network structure. The number of nodes for diazotrophs and bacterivores was higher in grassland than in cropland and bare land. Random forest analysis revealed that six bacterivore genera Cephalobus, Protorhabditis, Acrobeloides, Mesorhabditis, Anaplectus, and Monhystera had significant effects on diazotrophs. Bacterivores were found to have predominantly negative effects in bare land. Different bacterivores had differing effects with respect to driving changes in diazotroph community structure. Structural equation model showed that land use could control diazotroph community composition by altering soil properties and regulating abundance of bacterivores. These findings accordingly enhance our current understanding of mechanisms underlying the influence of land use patterns on diazotrophs from the perspective of soil food webs.
Influence of genomic structural variations and nutritional conditions on the emergence of quorum sensing-dependent gene regulation defects in Burkholderia glumae
Authors: Kang Minhee , Lim Jae Yun , Kim Jinwoo , Hwang Ingyu , Goo Eunhye
Published: July 2022

Bacteria often change their genetic and physiological traits to survive in harsh environments. To determine whether, in various strains of Burkholderia glumae, genomic diversity is associated with the ability to adapt to ever-changing environments, whole genomes of 44 isolates from different hosts and regions were analyzed. Whole-genome phylogenetic analysis of the 44 isolates revealed six clusters and two divisions. While all isolates possessed chromosomes 1 and 2, strains BGR80S and BGR81S had one chromosome resulting from the merging of the two chromosomes. Upon comparison of genomic structures to the prototype BGR1, inversions, deletions, and rearrangements were found within or between chromosomes 1 and/or 2 in the other isolates. When three isolates—BGR80S, BGR15S, and BGR21S, representing clusters III, IV, and VI, respectively—were grown in Luria-Bertani medium, spontaneous null mutations were identified in qsmR encoding a quorum-sensing master regulator. Six days after subculture, qsmR mutants were found at detectable frequencies in BGR15S and BGR21S, and reached approximately 40% at 8 days after subculture. However, the qsmR mutants appeared 2 days after subculture in BGR80S and dominated the population, reaching almost 80%. No qsmR mutant was detected at detectable frequency in BGR1 or BGR13S. The spontaneous qsmR mutants outcompeted their parental strains in the co-culture. Daily addition of glucose or casamino acids to the batch cultures of BGR80S delayed emergence of qsmR mutants and significantly reduced their incidence. These results indicate that spontaneous qsmR mutations are correlated with genomic structures and nutritional conditions.
Synergistic Antimicrobial Effect of Antimicrobial Peptides CATH-1, CATH-3, and PMAP-36 With Erythromycin Against Bacterial Pathogens
Authors: Lu Yi , Tian Hongliang , Chen Runqiu , Liu Qian , Jia Kaixiang , Hu Dong-Liang , Chen Hongwei , Ye Chao , Peng Lianci , Fang Rendong
Published: July 2022

With the increasing bacterial resistance to traditional antibiotics, there is an urgent need for the development of alternative drugs or adjuvants of antibiotics to enhance antibacterial efficiency. The combination of antimicrobial peptides (AMPs) and traditional antibiotics is a potential alternative to enhance antibacterial efficiency. In this study, we investigated the synergistic bactericidal effect of AMPs, including chicken (CATH-1,−2,−3, and -B1), mice (CRAMP), and porcine (PMAP-36 and PR-39) in combination with conventional antibiotics containing ampicillin, tetracycline, gentamicin, and erythromycin against Staphylococcus aureus, Salmonella enteritidis, and Escherichia coli. The results showed that the minimum bactericidal concentration (MBC) of CATH-1,−3 and PMAP-36 was lower than 10 μM, indicating that these three AMPs had good bacterial activity against S. aureus, S. enteritidis, and E. coli. Then, the synergistic antibacterial activity of AMPs and antibiotics combination was determined by the fractional bactericidal concentration index (FBCI). The results showed that the FBCI of AMPs (CATH-1,−3 and PMAP-36) and erythromycin was lower than 0.5 against bacterial pathogens, demonstrating that they had a synergistic bactericidal effect. Furthermore, the time-killing kinetics of AMPs (CATH-1,−3 and PMAP-36) in combination with erythromycin showed that they had a continuous killing effect on bacteria within 3 h. Notably, the combination showed lower hemolytic activity and cytotoxicity to mammal cells compared to erythromycin and peptide alone treatment. In addition, the antibacterial mechanism of CATH-1 and erythromycin combination against E. coli was studied. The results of the scanning electron microscope showed that CATH-1 enhanced the antibacterial activity of erythromycin by increasing the permeability of bacterial cell membrane. Moreover, the results of bacterial migration movement showed that the combination of CATH-1 and erythromycin significantly inhibits the migration of E. coli. Finally, drug resistance analysis was performed and the results showed that CATH-1 delayed the emergence of E. coli resistance to erythromycin. In conclusion, the combination of CATH-1 and erythromycin has synergistic antibacterial activity and reduces the emergence of bacterial drug resistance. Our study provides valuable information to develop AMPs as potential substitutes or adjuvants for traditional antibiotics.
The Mechanisms of Ferroptosis and the Applications in Tumor Treatment: Enemies or Friends?
Authors: Tan Shuzheng , Kong Ying , Xian Yongtong , Gao Pengbo , Xu Yue , Wei Chuzhong , Lin Peixu , Ye Weilong , Li Zesong , Zhu Xiao
Published: July 2022

Ferroptosis, as a newly discovered non-apoptotic cell death mode, is beginning to be explored in different cancer. The particularity of ferroptosis lies in the accumulation of iron dependence and lipid peroxides, and it is different from the classical cell death modes such as apoptosis and necrosis in terms of action mode, biochemical characteristics, and genetics. The mechanism of ferroptosis can be divided into many different pathways, so it is particularly important to identify the key sites of ferroptosis in the disease. Herein, based on ferroptosis, we analyze the main pathways in detail. More importantly, ferroptosis is linked to the development of different systems of the tumor, providing personalized plans for the examination, treatment, and prognosis of cancer patients. Although some mechanisms and side effects of ferroptosis still need to be studied, it is still a promising method for cancer treatment.
Assessment of Binge-Like Eating of Unsweetened vs. Sweetened Chow Pellets in BALB/c Substrains
Authors: Sena Katherine D. , Beierle Jacob A. , Richardson Kayla T. , Kantak Kathleen M. , Bryant Camron D.
Published: July 2022

Binge eating disorder (BED) is defined as chronic episodes of consuming large amounts of food in less than 2 h. Binge eating disorder poses a serious public health problem, as it increases the risk of obesity, type II diabetes, and heart disease. Binge eating is a highly heritable trait; however, its genetic basis remains largely unexplored. We employed a mouse model for binge eating that focused on identifying heritable differences between inbred substrains in acute and escalated intake of sucrose-sweetened palatable food vs. unsweetened chow pellets in a limited, intermittent access paradigm. In the present study, we examined two genetically similar substrains of BALB/c mice for escalation in food consumption, incubation of craving after a no-food training period, and compulsive-like food consumption in an aversive context. BALB/cJ and BALB/cByJ mice showed comparable levels of acute and escalated consumption of palatable food across training trials. Surprisingly, BALB/cByJ mice also showed binge-like eating of the unsweetened chow pellets similar to the escalation in palatable food intake of both substrains. Finally, we replicated the well-documented decrease in anxiety-like behavior in BALB/cByJ mice in the light-dark conflict test that likely contributed to greater palatable food intake than BALB/cJ in the light arena. To summarize, BALB/cByJ mice show binge-like eating in the presence and absence of sucrose. Possible explanations for the lack of selectivity in binge-like eating across diets (e.g., novelty preference, taste) are discussed.
Plasticity of monocytes and macrophages in cirrhosis of the liver
Authors: Geng Anne , Flint Emilio , Bernsmeier Christine
Published: July 2022

Cirrhosis of the liver is a systemic condition with raising prevalence worldwide. Patients with cirrhosis are highly susceptible to develop bacterial infections leading to acute decompensation and acute-on-chronic liver failure both associated with a high morbidity and mortality and sparse therapeutic options other than transplantation. Mononuclear phagocytes play a central role in innate immune responses and represent a first line of defence against pathogens. Their function includes phagocytosis, killing of bacteria, antigen presentation, cytokine production as well as recruitment and activation of immune effector cells. Liver injury and development of cirrhosis induces activation of liver resident Kupffer cells and recruitment of monocytes to the liver. Damage- and pathogen-associated molecular patterns promote systemic inflammation which involves multiple compartments besides the liver, such as the circulation, gut, peritoneal cavity and others. The function of circulating monocytes and tissue macrophages is severely impaired and worsens along with cirrhosis progression. The underlying mechanisms are complex and incompletely understood. Recent ‘omics’ technologies help to transform our understanding of cellular diversity and function in health and disease. In this review we point out the current state of knowledge on phenotypical and functional changes of monocytes and macrophages during cirrhosis evolution in different compartments and their role in disease progression. We also discuss the value of potential prognostic markers for cirrhosis-associated immuneparesis, and future immunotherapeutic strategies that may reduce the need for transplantation and death.
Self-Reported Measures Have a Stronger Association With Dizziness-Related Handicap Compared With Physical Tests in Persons With Persistent Dizziness
Authors: Kristiansen Lene , Magnussen Liv H. , Wilhelmsen Kjersti T. , Maeland Silje , Nordahl Stein Helge G. , Hovland Anders , Clendaniel Richard , Boyle Eleanor , Juul-Kristensen Birgit
Published: July 2022

Background

Associations between dizziness-related handicap and a variety of self-reported measures have been reported. However, research regarding associations between dizziness-related handicap and aspects of functioning that includes both physical tests and self-reported measures is scarce.

Objective

The purpose of the study was to describe the variations in signs and symptoms in people with persistent dizziness using physical tests and self-reported outcomes across three severity levels of the Dizziness Handicap Inventory (DHI) and investigate their associations with the DHI.

Method

Participants with persistent dizziness (n = 107) were included in this cross-sectional study. The participants underwent (1) physical tests (gait tests, grip strength, body flexibility, and movement-induced dizziness) and completed questionnaires regarding (2) psychological measures (Mobility Inventory of Agoraphobia, Body Sensation Questionnaire, Agoraphobic Cognitions Questionnaire, and Hospital Depression and Anxiety Questionnaire), and (3) fatigue, dizziness severity, and quality of life (Chalders Fatigue Scale, Vertigo Symptom Scale-Short Form, and EQ visual analog scale), in addition to the DHI. Data were presented by descriptive statistics for three DHI severity levels (mild, moderate, and severe). A multiple linear backward regression analysis was conducted for each group of measures in relation to the DHI total score, with additional analyses adjusting for age and sex. Based on these results, significant associations were tested in a final regression model.

Results

With increasing severity levels of DHI, the participants demonstrated worse performance on most of the physical tests (preferred and fast gait velocity, dizziness intensity after head movements), presented with worse scores on the self-reported measures (avoidance behavior, fear of bodily sensation, fear of fear itself, psychological distress, fatigue, dizziness severity, quality of life). After adjusting for age and sex, significant associations were found between total DHI and avoidance behavior, psychological distress, dizziness severity, and quality of life, but not with any of the physical tests, explaining almost 56% of the variance of the DHI total score.

Conclusion

There was a trend toward worse scores on physical tests and self-reported measurements with increasing DHI severity level. The DHI seems to be a valuable tool in relation to several self-reported outcomes; however, several signs and symptoms may not be detected by the DHI, and thus, a combination of outcomes should be utilized when examining patients with persistent dizziness.
Non-Linear Association Between Serum Alkaline Phosphatase and 3-Month Outcomes in Patients With Acute Stroke: Results From the Xi'an Stroke Registry Study of China
Authors: Guo Weiyan , Liu Zhongzhong , Lu Qingli , Liu Pei , Lin Xuemei , Wang Jing , Wang Yuanji , Chang Qiaoqiao , Wang Fang , Wu Songdi
Published: July 2022

Background

Alkaline phosphatase (ALP) is associated with an increased risk of cardiovascular events and is closely related to adverse outcomes after stroke. However, the regional investigation into the associations of ALP with acute stroke (AS) outcomes is limited. This study aimed to identify the association between serum ALP levels and clinical outcomes 3 months after AS in the Xi'an district of China.

Methods

We enrolled all patients with AS from 4 hospitals in the Xi'an district from January to December 2015. ALP levels and related patient information were collected at admission, and the events of stroke outcomes were followed up 1 and 3 months after diagnosis. ALP levels were analyzed as continuous variables and quartiles (Q1–Q4). The outcomes included all-cause mortality, recurrent stroke, and poor functional outcomes (modified Rankin Scale score of 3–6) within 3 months. A multivariate logistic regression and interaction analyses were performed to evaluate the independent association between serum ALP level and 3-month stroke outcomes.

Results

Overall, 2,799 patients with AS were enrolled in this study. The mean age was 63.9 ± 12.5 years. In the Q4 (≥93.0 U/L) group, the incidences of all-cause mortality, recurrent stroke, and poor functional outcomes were 7.8, 2.7, and 24.9%, respectively. After being adjusted for confounding variables, patients in Q4 (≥93.0 U/L) were related to an increased risk of all-cause mortality [odds ratio (OR) = 2.17, 95% CI: 1.19–3.96; P = 0.011] and patients in Q3 (76.8–92.9 U/L) were related to a lower risk of recurrent stroke (OR = 0.37, 95% CI: 0.14–0.97; P = 0.043) at the 3-month time point, compared to those in Q2 (63.0–76.7 U/L). The optimal range of ALP for all-cause mortality was seen in Q2, with a nadir level of 70 U/L. However, differences were statistically insignificant between ALP levels and poor functional outcomes (P > 0.05). Moreover, there was no significant interaction between ALP levels and age, gender, drinking status, smoking status, or pneumonia (P > 0.05) for all outcomes.

Conclusion

Non-linear associations were observed between serum ALP levels and 3-month outcomes in patients with AS. It might be beneficial to reduce the risk of all-cause mortality and recurrent stroke by maintaining ALP at optimal ranges.
Adjunctive Treatment With Eslicarbazepine Acetate for Adults and Children With Focal-Onset Epilepsy: A Meta-Analysis
Authors: Fei Yanqing , Shi Ruting , Song Zhi
Published: July 2022

Background

The efficacy and tolerability of eslicarbazepine acetate (ESL) in adults and children with focal-onset epilepsy (FOE) according to the dose remain to be validated. A meta-analysis based on randomized controlled trials (RCTs) was therefore conducted as a summary.

Methods

Relevant RCTs were collected by systematic searching the electronic databases of PubMed, Cochrane's Library, Embase, Wanfang and CNKI from inception to May 16, 2022. The random-effect model was adopted to pool the results by incorporating the possible heterogeneity. Efficacy outcomes including responsive rate and effective rate, defined as cases with 50 and ≥75% reduction in seizure frequency compared to baseline, were determined, respectively. Incidence of severe adverse events (AE) leading to drug discontinuation was also evaluated.

Results

Ten studies including 2,565 people with epilepsy contributed to the meta-analysis. For adults, ESL 400 mg/d did not improve the response rate or the effective rate; ESL 800 mg/d was associated with improved response rate (odds ratio [OR] 2.16, 95% confidence interval [CI]: 1.65–2.83, p < 0.001) and effective rate (OR 2.16, 95% CI: 1.41–3.30, p < 0.001) without significantly increased severe AE (OR 1.58, 95% CI: 0.90–2.78, p = 0.11); ESL 1,200 mg/d improved response rate (OR 2.49, p < 0.001) and effective rate (OR 3.09, p = 0.04), but significantly increased severe AE (OR 3.72, p < 0.001). For children, ESL also did not significantly improve the response rate (OR 1.76, p = 0.22) or the effective rate (OR 2.17, p = 0.13).

Conclusion

ESL 800 mg/d is effective and well-tolerated as adjuvants for adults with FOE. Efficacy of ESL in children with FOE should be further evaluated.