bluuebunny/crossref_metadata_2025 huggingface dataset:
The Relationship between Positive Thinking, Empathy Ability and Communication Ability of Some Dental Hygiene Students
Authors:   Dept. of Dental Hygiene, Songwon University, Professor, Lim Sun-A
Published: July 2021

Objectives: This study investigates the relationship between of positive thinking and empathy ability on the communication ability of dental hygiene students. Methods: First, the research objectives and methods were explained to students enrolled in the department of dental hygiene in the G area, and 160 participants were selected. An independent t-test, a one-way ANOVA, and a Scheffé test were used to measure participants’ positive thinking, empathy ability and communication ability. The correlations of positive thinking and empathy ability with communication ability were analyzed using Pearson’s correlation test, and the factors that impact communication ability were analysed using a stepwise multiple regression. Results: Higher levels of positive thinking and empathy ability correlated with better communication ability. Subjective satisfaction, goal pursuit, cognitive empathy ability, and emotional empathy ability were identified as factors that impact the communication ability of dental hygiene students. Conclusions: A dental hygiene education program designed to improve the communication ability of dental hygiene students is needed. Communication ability is a core competency that can be increased by improving positive thinking and empathy ability.
Effects of COVID-19 Online Learning Participation on Dental Hygiene Students Self-Control
Authors:   Dept. of Dental Hygiene, College of Health and Welfare, Silla University, Associate professor, Kang Hyun-Kyung , Lee Ji-Young ,   Dept. of Dental Hygiene, College of Health and Welfare, Silla University, Lecturer
Published: July 2021

Objectives: The purpose of this study is to measure dental hygiene students’ self-control, self-confidence, self-regulation, and task difficulty preferences for online learning; it also seeks to identify the factors that influence dental hygiene students’ self-control. Methods: An independent t-test and one-way ANOVA were used to analyze differences in the self-control, self-confidence, self-regulation, and task difficulty preference of dental hygiene students currently enrolled in two universities in Busan. A Scheffe test was conducted, and a multiple linear regression analysis of the factors impacting self-control was conducted as well. Results: The results show that confidence and self-regulatory efficacy significantly influence participants’ self-control. Conclusions: Higher self-confidence and self-regulation are associated with greater self-control
The Effect of Education on Toothbrushing Methods and Perceptions of Toothbrushing among Elementary School Students in Busan
Authors:   Dept. of Dental Hygiene, College of Dentistry, Gangneung-Wonju National University, Professor, Bae Soo-Myoung , Kim Kyung-Min ,   Dept. of Research Institute Health for Functional Material, Dong-Eui University, Research professor
Published: July 2021

Objectives: This study examines the effect of education on toothbrushing and oral health on the oral health behaviors and knowledge of fourth graders in Busan. Methods: Data were collected from March to December 2020 via a questionnaire; a total of 57 fourth graders in D-gu, B city participated. Results: Respondents’ knowledge of oral health increased after participation in an oral health education program. Positive changes to participants’ frequency, duration, and method of toothbrushing were observed. Specifically, participants shifted from horizontal or vertical toothbrushing methods to rolling brushing after taking part in the educational program. Conclusions: Dental health education improves elementary school students’ knowledge of oral health and leads to behavioral changes that can improve oral health.
Factors Influencing Preventive Behavior against COVID-19 among Dental Hygiene Students
Authors:   Dept. of Dental Hygiene, Dongju college, Assistant professor, Lim Hyun-Ju , Lee Ji-Young ,   Dept. of Dental Hygiene, Dongju college, Adjunct professor, Hwang Se-Hyun ,   Dept. of Dental Hygiene, Dongju college, Lecturer
Published: July 2021

Objectives: The purpose of this study is to investigate factors influencing preventive behavior against COVID-19 among college students majoring in dental hygiene. Methods: This study is based on a questionnaire survey via online collected from students currently majoring in dental hygiene from 2 colleges in Busan area. Subjects were informed of the purpose and the necessity of the study and agreed to participate in the investigation beforehand. Results: Preventive behavior against COVID-19 was highly affected by attitude and knowledge of COVID-19. Conclusions: Knowledge and attitude toward COVID-19 have significant effect on preventive behavior against COVID-19
The Relationship between Oral Health Knowledge and Understanding of Oral Health Information according to Whether Some Adults have a Private Dental Health Insurance
Authors:   E&Mi wooridul Dental Hospital, Team leader, Jung Im-Hee , Kim Min-Ji ,   Dept. of Dental Hygiene, Division of Health Sciences, Dongseo University, Associate professor
Published: July 2021

Objectives: More and more private dental insurance products are becoming available in Korea, but little is known about how well purchasers of these products understand them. Methods: Some adults conducted a survey to check their oral health knowledge according to whether they joined for private dental health insurance. Results: Adults enrolled in private dental insurance have high levels of knowledge and understanding about oral health. Participants’ knowledge of oral health positively correlated with their understanding of oral health information (r=.408, p<0.01). Conclusions: Education targeted at improving individuals’ understanding of oral health should be strengthened in the future, as patients’ general knowledge of oral health supports the prevention and treatment of oral disease.
Análisis discursivo sobre el sentido de comunidad de los latinoamericanos en Málaga
Authors: Millán-Franco Mario , Domínguez de la Rosa Laura , Gómez-Jacinto Luis , Hombrados-Mendieta María Isabel , García-Cid Alba
Published: July 2021

This article presents the results of a qualitative study whose interest lies in understanding how Latin Americans residing in Malaga build their sense of community. To collect information, 23 in-depth interviews were conducted with people from Latin America. Through a detailed analysis of these interviews, three Interpretative Repertoires were identified: The diffuse limits of the sense of community, communities as the backbone of the sense of community, and the language of love as a facilitator of the sense of community. The importance of formal and informal organizations for the development of a sense of local community is highlighted. The sense of community, related to the place of residence, is the result of a mental process of overlapping senses of community towards communities, where the language of love is the protagonist. A limitation, and the potential of this study, is that the sense of community is the subjective manifestation of the community, so the experiences of each person influence its social construction.
Enhanced visible light absorption in layered Cs3Bi2Br9 through mixed-valence Sn(II) / Sn(IV) doping
Authors: Krajewska Chantalle , Kavanagh Seán , Zhang Lina , Kubicki Dominik , Dey Krishanu , Gałkowski Krzysztof , Grey Clare , Stranks Samuel , Walsh Aron , Scanlon David , Palgrave Robert
Published: July 2021

Lead-free halides with perovskite-related structures, such as the vacancy-ordered perovskite Cs3Bi2Br9, are of interest for photovoltaic and optoelectronic applications. Addition of SnBr2 to the solution-phase synthesis of Cs3Bi2Br9 leads to substitution of up to 7% of the Bi(III) ions by equal quantities of Sn(II) and Sn(IV). The resulting mixed-valence compounds show intense visible and near infrared absorption due to intervalence charge transfer, intermediate band transitions. Sn(II) and Sn(IV) defects occupy neighbouring B-cation sites, forming a double-substitution complex. Unusually for a Sn(II) compound, the material shows minimal changes in optical and structural properties after 12 months storage in air. Our calculations suggest the stabilisation of Sn(II) within the double substitution complex contributes to this unusual stability. These results expand upon research on inorganic mixed-valent halides to a new, layered structure, and offer insights into the tuning, doping mechanisms, and structure-property relationships of lead-free vacancy-ordered perovskite structures.
Prognostic factors in colorectal cancer
Authors: Kit O. I. , Gevorkyan Yu. A. , Soldatkina N. V. , Timoshkina N. N. , Kharagezov D. A. , Kaymakchi D. O. , Poluektov S. I. , Dashkov A. V. , Gudtskova T. N.
Published: July 2021

Aim: to evaluate prognostic factors in colorectal cancer.

Material and methods: published data (publications in PubMed, Scopus, eLIBRARY databases) and own results of treatment of 47 patients with T2-4N0-2M0 colon cancer in 2017–2018. The following prognostic factors were studied: metastasis in regional lymph nodes, tumor site, CEA level, KRAS and BRAF mutation status, microsatellite instability, MUSASHI2, p53, VEGF.

Results: a correlation between tumor progression and the status of regional lymph nodes demonstrated significant differences (p = 0.038): in N0, the risk of progression was 3.8%, in N1 — 14.9%, in N2 — 43.6%. Statistical processing of the results did not reveal significant differences between groups of patients without and with cancer generalization by their age, gender, tumor site, type of lymph node dissection, T stage, differentiation of adenocarcinoma, levels of CEA, mutations of KRAS, MSI, p53, MUSASHI2, VEGF. We used these prognostic factors to determine biological features of the tumor, its aggressiveness and treatment approaches.

Conclusions: the status of regional lymph nodes remains the main factor in determining the prognosis of a colon tumor and in the medical therapy appointment. Molecular genetic factors are currently of great importance for determining tactics in personalized medical treatment.
Feasibility of a Sheep Welfare Assessment Tool in the Pre-export Phase of Australian Live Export Industry
Authors: Collins Teresa , Anthony Ursula M. C. , Dunston-Clarke Emma J. , Fleming Patricia A.
Published: July 2021

Sheep are exposed to numerous stressors and environments during the pre-export phase of the live export industry. Establishing how animal behavior, health and demeanor reflect their experiences prior to sea transport is the first step toward testing the suitability and practicality of animal welfare measures. A total of 240 merino wethers originating from four farms were assessed at four locations in the live export chain: on farm, upon arrival to the registered export feedlot (Fe1), prior to departing the feedlot (Fe2) and 30 min post loading onto a live export vessel. Each of these locations and time points represent relevant assessment points as part of the commercial live export process. Pen-side behavioral and health measures were collected. Video footage was collected and edited to provide 48 30–45 s duration clips that were then scored by 12 assessors against 10 demeanor terms using a Qualitative Behavioral Assessment (QBA) methodology; data were analyzed using Principal Components (PC) analysis. Repeated Measures ANOVAs tested for variation in each dependent measure across each location and time point. There were low levels of health issues recorded overall; however, seven health and behavior measures significantly varied across the locations and time points. Most vocalizing was recorded on farm; most drinking, eating and resting behaviors were recorded at Fe1 and ruminating at Fe2; while the highest percentage of wethers with ocular discharge and lameness was on the vessel. For QBA, PC1 explained 30.5% of the variability, with agitated and nervous loaded to one end of the axis and calm and relaxed loaded to the opposing end. PC2 explained 24.5% of the variability, with interested, alert and sociable loaded to one end of the axis and lethargic loaded to the opposing end. Spearman's rank correlations between behavior, health and PC scores indicated that wethers eating, ruminating and resting were scored as more calm/relaxed, while those scored as more agitated/nervous or/ lethargic were also likely to vocalize. Determining how wethers respond to the different environments in the immediate pre-export phase of the journey informs on their welfare and the practicality of using a behavior tool to assess animal welfare.
The Effect of Background Noise on a “Studying for an Exam” Task in an Open-Plan Study Environment: A Laboratory Study
Authors: Braat-Eggen Ella , Reinten Jikke , Hornikx Maarten , Kohlrausch Armin
Published: July 2021

Students can be disturbed by background noise while working in an open-plan study environment. To improve the acoustic quality of open-plan study environments a study was done on the influence of different sound scenarios on students working on a typical student task, “studying for an exam”. Three sound scenarios and a quiet reference sound scenario were developed, based on the sound environment of a real open-plan study environment, with a varying number of talkers in the background and different reverberation times of the study environment. Seventy students worked on a set of tasks simulating a “studying for an exam” task while being exposed to the sound scenarios. This task comprises a reading comprehension task with text memory by delayed answering questions about the text, with additional tasks being performed in the gap between studying the text and retrieving. These additional tasks are a mental arithmetic task and a logical reasoning task. Performance, self-estimated performance and disturbance of students were measured. No significant effect of the sound scenarios was found on performance of students working on the reading comprehension task with text memory and the mental arithmetic task. However, a significant effect of sound was found on performance of students working on the logical reasoning task. Furthermore, a significant effect of the sound scenarios was found on self-estimated performance and perceived disturbance for all tasks from which the reading comprehension task with text memory was the most disturbed task. It is argued that the absence of a detrimental sound effect on the performance of students working on a reading comprehension task with text memory is a result of focusing due to task engagement and task difficulty, both aspects working as a “shield against distraction”.
Long Non-coding RNA ASNR Targeting miR-519e-5p Promotes Gastric Cancer Development by Regulating FGFR2
Authors: Chen Zihao , Li Yong , Tan Bibo , Li Fang , Zhao Qun , Fan Liqiao , Zhang Zhidong , Zhao Xuefeng , Liu Yu , Wang Dong
Published: July 2021

Gastric cancer (GC), as a common gastrointestinal tumor, is an important cause of death from cancer all around the world. Long non-coding RNAs (lncRNAs), a novel class of transcripts, have attracted great attention of researchers. However, the mechanisms of the clinical significance of most lncRNAs in human cancer are mainly undocumented. This research desires to explore the clinical significance, biological function, and mechanism of Lnc_ASNR (apoptosis suppressing-non-coding RNA) in GC. Cell proliferation, cell cycle, cell migration, and invasion abilities were respectively determined by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT), flow cytometry, wound healing, and Transwell assay (Sigma-Aldrich, St. Louis, MO, United States). The association of Lnc_ASNR, miR-519e-5p, and fibroblast growth factor receptor 2 (FGFR2) was evaluated via luciferase reporter experiments. The tumor xenograft assay was conducted to confirm the results of cell experiments. High expressed Lnc_ASNR was detected in both GC cells and tissues using qRT-PCR. Downregulated Lnc_ASNR could reduce proliferation, migration, and invasion in GC cells, while upregulated Lnc_ASNR could promote the cell proliferation, migration, and invasion. Moreover, the effect of Lnc_ASNR on migration and invasion ability is closely related to epithelial-mesenchymal transition (EMT). The bioinformatics analysis, luciferase assay, and Western blot demonstrated that Lnc_ASNR inhibited miR-519e-5p expression but increased FGFR2 expression. Lnc_ASNR and FGFR2 were both targeted to miR-519e-5p, and they were negatively correlated with the expression of miR-519e-5p. All investigations indicated that Lnc_ASNR functioned as a ceRNA targeting miR-519e-5p and facilitated GC development by regulating the pathway of miR-519e-5p/FGFR2.
Plasma LOX-Products and Monocyte Signaling Is Reduced by Adjunctive Cyclooxygenase-2 Inhibitor in a Phase I Clinical Trial of Tuberculosis Patients
Authors: Jøntvedt Jørgensen Marthe , Nore Kristin G. , Aass Hans Christian D. , Layre Emilie , Nigou Jérôme , Mortensen Rasmus , Tasken Kjetil , Kvale Dag , Jenum Synne , Tonby Kristian , Dyrhol-Riise Anne Ma
Published: July 2021

Introduction

Eicosanoids and intracellular signaling pathways are potential targets for host-directed therapy (HDT) in tuberculosis (TB). We have explored the effect of cyclooxygenase 2 inhibitor (COX-2i) treatment on eicosanoid levels and signaling pathways in monocytes.

Methods

Peripheral blood mononuclear cells isolated from TB patients included in a randomized phase I clinical trial of standard TB treatment with (n=21) or without (n=18) adjunctive COX-2i (etoricoxib) were analyzed at baseline, day 14 and day 56. Plasma eicosanoids were analyzed by ELISA and liquid chromatography-mass spectrometry (LC-MS), plasma cytokines by multiplex, and monocyte signaling by phospho-flow with a defined set of phospho-specific antibodies.

Results

Lipoxygenase (LOX)-derived products (LXA4 and 12-HETE) and pro-inflammatory cytokines were associated with TB disease severity and were reduced during TB therapy, possibly accelerated by adjunctive COX-2i. Phosphorylation of p38 MAPK, NFkB, Erk1/2, and Akt in monocytes as well as plasma levels of MIG/CXCL9 and procalcitonin were reduced in the COX-2i group compared to controls.

Conclusion

COX-2i may reduce excess inflammation in TB via the LOX-pathway in addition to modulation of phosphorylation patterns in monocytes. Immunomodulatory effects of adjunctive COX-2i in TB should be further investigated before recommended for use as a HDT strategy.
High-Throughput Screening Identifies MicroRNAs Regulating Human PCSK9 and Hepatic Low-Density Lipoprotein Receptor Expression
Authors: van Solingen Coen , Oldebeken Scott R. , Salerno Alessandro G. , Wanschel Amarylis C. B. A. , Moore Kathryn J.
Published: July 2021

Investigations into the regulatory mechanisms controlling cholesterol homeostasis have proven fruitful in identifying low-density lipoprotein (LDL)-lowering therapies to reduce the risk of atherosclerotic cardiovascular disease. A major advance was the discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9), a secreted protein that binds the LDL receptor (LDLR) on the cell surface and internalizes it for degradation, thereby blunting its ability to take up circulating LDL. The discovery that loss-of-function mutations in PCSK9 lead to lower plasma levels of LDL cholesterol and protection from cardiovascular disease led to the therapeutic development of PCSK9 inhibitors at an unprecedented pace. However, there remain many gaps in our understanding of PCSK9 regulation and biology, including its posttranscriptional control by microRNAs. Using a high-throughput region(3′-UTR) of human microRNA library screen, we identified microRNAs targeting the 3′ untranslated region of human PCSK9. The top 35 hits were confirmed by large-format PCSK9 3′-UTR luciferase assays, and 10 microRNAs were then selected for further validation in hepatic cells, including effects on PCSK9 secretion and LDLR cell surface expression. These studies identified seven novel microRNAs that reduce PCSK9 expression, including miR-221-5p, miR-342-5p, miR-363-5p, miR-609, miR-765, and miR-3165. Interestingly, several of these microRNAs were also found to target other genes involved in LDLR regulation and potently upregulate LDLR cell surface expression in hepatic cells. Together, these data enhance our understanding of post-transcriptional regulators of PCSK9 and their potential for therapeutic manipulation of hepatic LDLR expression.
Finding Fitting Solutions to Assessment of Indigenous Young Children’s Learning and Development: Do It in a Good Way
Authors: Ball Jessica
Published: July 2021

Standardized, norm-referenced assessments of young children’s learning and development pose a number of challenges when used with Indigenous children, beginning with the very notion of the construct “early childhood” that runs counter to some Indigenous ways of knowing and being. Indigenous community leaders and knowledge keepers reject the idea that all children should develop according to a homogenizing universal standard that is not grounded in specific culturally based goals and practices surrounding children’s development and does not respect each child’s unique character. Three key problems arise with creating appropriate assessment of Indigenous young children’s learning and development: 1) assessment in early childhood programs is often done from the perspective of whether children are on track to be ready for school; 2) school systems, early childhood programs, and practitioners face a barrage of pressure to measure children’s “progress” against universalist norms derived from Euro-Western ways of knowing and goals for children’s development; and 3) knowledge of diverse Indigenous young children’s varied lived experiences in today’s urban and rural communities is extremely limited. This paper discusses these obstacles and draws from the author’s many years of collaborating with Indigenous children, families, and communities to co-create culturally relevant assessment in a good way.
Neuropeptide Y Plays an Important Role in the Relationship Between Brain Glucose Metabolism and Brown Adipose Tissue Activity in Healthy Adults: A PET/CT Study
Authors: Zhang Qiongyue , Miao Qing , Yang Yehong , Lu Jiaying , Zhang Huiwei , Feng Yonghao , Wu Wei , Zhu Xiaoming , Xiang Boni , Sun Quanya , Guan Yihui , Li Yiming , Zuo Chuantao , Ye Hongying
Published: July 2021

Introduction

Brown adipose tissue (BAT) becomes the favorite target for preventing and treating metabolic diseases because the activated BAT can produce heat and consume energy. The brain, especially the hypothalamus, which secretes Neuropeptide Y (NPY), is speculated to regulate BAT activity. However, whether NPY is involved in BAT activity’s central regulation in humans remains unclear. Thus, it’s essential to explore the relationship between brain glucose metabolism and human BAT activity.

Methods

A controlled study with a large sample of healthy adults used Positron emission tomography/computed tomography (PET/CT) to noninvasively investigate BAT’s activity and brain glucose metabolism in vivo. Eighty healthy adults with activated BAT according to the PET/CT scan volunteered to be the BAT positive group, while 80 healthy adults without activated BAT but with the same gender, similar age, and BMI, scanning on the same day, were recruited as the control (BAT negative). We use Statistical parametric mapping (SPM) to analyze the brain image data, Picture Archiving & Communication System (PACS), and PET/CT Viewer software to calculate the semi-quantitative values of brain glucose metabolism and BAT activity. ELISA tested the levels of fasting plasma NPY. The multiple linear regression models were used to analyze the correlation between brain glucose metabolism, the level of NPY, and the BAT activity in the BAT positive group.

Results

(1) Compared with controls, BAT positive group showed significant metabolic decreases mainly in the right Insula (BA13a, BA13b) and the right claustrum (uncorrected P <0.01, adjusted BMI). (2) The three brain regions’ semi-quantitative values in the BAT positive group were significantly lower than the negative group (all P values < 0.05). (3) After adjusting for age, gender, BMI, and outside temperature, there was a negative correlation between brain metabolic values and BAT activity (all P values < 0.05). However, after further adjusting for NPY level, there were no significant differences between the BA13b metabolic values and BAT activity (P>0.05), while the correlation between the BA13a metabolic values and BAT activity still was significant (P< 0.05).

Conclusions

Regional brain glucose metabolism is closely related to healthy adults’ BAT activity, which may be mediated by NPY.
Weighted Gene Co-expression Network Analysis Identified a Novel Thirteen-Gene Signature Associated With Progression, Prognosis, and Immune Microenvironment of Colon Adenocarcinoma Patients
Authors: Zhang Cangang , Zhao Zhe , Liu Haibo , Yao Shukun , Zhao Dongyan
Published: July 2021

Colon adenocarcinoma (COAD) is one of the most common malignant tumors and has high migration and invasion capacity. In this study, we attempted to establish a multigene signature for predicting the prognosis of COAD patients. Weighted gene co-expression network analysis and differential gene expression analysis methods were first applied to identify differentially co-expressed genes between COAD tissues and normal tissues from the Cancer Genome Atlas (TCGA)-COAD dataset and GSE39582 dataset, and a total of 309 overlapping genes were screened out. Then, our study employed TCGA-COAD cohort as the training dataset and an independent cohort by merging the GES39582 and GSE17536 datasets as the testing dataset. After univariate and multivariate Cox regression analyses were performed for these overlapping genes and overall survival (OS) of COAD patients in the training dataset, a 13-gene signature was constructed to divide COAD patients into high- and low-risk subgroups with significantly different OS. The testing dataset exhibited the same results utilizing the same predictive signature. The area under the curve of receiver operating characteristic analysis for predicting OS in the training and testing datasets were 0.789 and 0.868, respectively, which revealed the enhanced predictive power of the signature. Multivariate Cox regression analysis further suggested that the 13-gene signature could independently predict OS. Among the 13 prognostic genes, NAT1 and NAT2 were downregulated with deep deletions in tumor tissues in multiple COAD cohorts and exhibited significant correlations with poorer OS based on the GEPIA database. Notably, NAT1 and NAT2 expression levels were positively correlated with infiltrating levels of CD8+ T cells and dendritic cells, exhibiting a foundation for further research investigating the antitumor immune roles played by NAT1 and NAT2 in COAD. Taken together, the results of our study showed that the 13-gene signature could efficiently predict OS and that NAT1 and NAT2 could function as biomarkers for prognosis and the immune response in COAD.
Lifespan-Associated Gene Expression Signatures of Recombinant BXD Mice Implicates Coro7 and Set in Longevity
Authors: Vitiello David , Dakhovnik Alexander , Statzer Cyril , Ewald Collin Y.
Published: July 2021

Although genetic approaches have identified key genes and pathways that promote longevity, systems-level approaches are less utilized. Here, we took advantage of the wealth of omics data characterizing the BXD family of mice. We associated transcript and peptide levels across five tissues from both female and male BXD isogenic lines with their median lifespan. We identified over 5000 genes that showed a longevity correlation in a given tissue. Surprisingly, we found less than 1% overlap among longevity-correlating genes across tissues and sex. These 1% shared genes consist of 51 genes, of which 13 have been shown to alter lifespan. Only two genes -Coro7 and Set- showed a longevity correlation in all tissues and in both sexes. While differential regulation of aging across tissues and sex has been reported, our systems-level analysis reveals two unique genes that may promote healthy aging in unique sex- and tissue-agnostic manner.
The Alterations in and the Role of the Th17/Treg Balance in Metabolic Diseases
Authors: Zhang Siwen , Gang Xiaokun , Yang Shuo , Cui Mengzhao , Sun Lin , Li Zhuo , Wang Guixia
Published: July 2021

Chronic inflammation plays an important role in the development of metabolic diseases. These include obesity, type 2 diabetes mellitus, and metabolic dysfunction-associated fatty liver disease. The proinflammatory environment maintained by the innate immunity, including macrophages and related cytokines, can be influenced by adaptive immunity. The function of T helper 17 (Th17) and regulatory T (Treg) cells in this process has attracted attention. The Th17/Treg balance is regulated by inflammatory cytokines and various metabolic factors, including those associated with cellular energy metabolism. The possible underlying mechanisms include metabolism-related signaling pathways and epigenetic regulation. Several studies conducted on human and animal models have shown marked differences in and the important roles of Th17/Treg in chronic inflammation associated with obesity and metabolic diseases. Moreover, Th17/Treg seems to be a bridge linking the gut microbiota to host metabolic disorders. In this review, we have provided an overview of the alterations in and the functions of the Th17/Treg balance in metabolic diseases and its role in regulating immune response-related glucose and lipid metabolism.
Migration of Lung Resident Group 2 Innate Lymphoid Cells Link Allergic Lung Inflammation and Liver Immunity
Authors: Mathä Laura , Romera-Hernández Mónica , Steer Catherine A. , Yin Yi Han , Orangi Mona , Shim Hanjoo , Chang ChihKai , Rossi Fabio M. , Takei Fumio
Published: July 2021

Group 2 innate lymphoid cells (ILC2s) are tissue resident in the lung and activated by inhaled allergensviaepithelial-derived alarmins including IL-33. Activated ILC2s proliferate, produce IL-5 and IL-13, and induce eosinophilic inflammation. Here, we report that intranasal IL-33 or the protease allergen papain administration resulted in increased numbers of ILC2s not only in the lung but also in peripheral blood and liver. Analyses of IL-33 treated parabiosis mice showed that the increase in lung ILC2s was due to proliferation of lung resident ILC2s, whereas the increase in liver ILC2s was due to the migration of activated lung ILC2s. Lung-derived ILC2s induced eosinophilic hepatitis and expression of fibrosis-related genes. Intranasal IL-33 pre-treatment also attenuated concanavalin A-induced acute hepatitis and cirrhosis. These results suggest that activated lung resident ILC2s emigrate from the lung, circulate, settle in the liver and promote type 2 inflammation and attenuate type 1 inflammation.
Auto-Antibody Production During Experimental Atherosclerosis in ApoE-/- Mice
Authors: Hutchinson Mark A. , Park Han-Sol , Zanotti Kimberly J. , Alvarez-Gonzalez Juan , Zhang Jing , Zhang Li , Telljohann Richard , Wang Mingyi , Lakatta Edward G. , Gearhart Patricia J. , Maul Robert W.
Published: July 2021

Current models stipulate that B cells and antibodies function during atherosclerosis in two distinct ways based on antibody isotype, where IgM is protective and IgG is inflammatory. To examine this model, we generated ApoE-/- Aid-/- mice, which are unable to produce IgG antibodies due to the absence of activation-induced deaminase (AID) but maintain high plasma cholesterol due to the absence of apolipoprotein E (APOE). We saw a dramatic decrease in plaque formation in ApoE-/- Aid-/- mice compared to ApoE-/- mice. Rigorous analysis of serum antibodies revealed both ApoE-/- and ApoE-/- Aid-/- mice had substantially elevated titers of IgM antibodies compared to C57BL/6J controls, suggesting a more complex dynamic than previously described. Analysis of antigen specificity demonstrated that ApoE-/- Aid-/- mice had elevated titers of antibodies specific to malondialdehyde-oxidized low density lipoprotein (MDA-oxLDL), which has been shown to block macrophage recruitment into plaques. Conversely, ApoE-/- mice showed low levels of MDA-oxLDL specificity, but had antibodies specific to numerous self-proteins. We provide evidence for a hierarchical order of antibody specificity, where elevated levels of MDA-oxLDL specific IgM antibodies inhibit plaque formation. If the level of MDA-oxLDL specific IgM is insufficient, self-reactive IgM and IgG antibodies are generated against debris within the arterial plaque, resulting in increased inflammation and further plaque expansion.
Mycobacterium tuberculosis Protein PE6 (Rv0335c), a Novel TLR4 Agonist, Evokes an Inflammatory Response and Modulates the Cell Death Pathways in Macrophages to Enhance Intracellular Survival
Authors: Sharma Neha , Shariq Mohd , Quadir Neha , Singh Jasdeep , Sheikh Javaid A. , Hasnain Seyed E. , Ehtesham Nasreen Z.
Published: July 2021

Mycobacterium tuberculosis(M. tb) is an intracellular pathogen that exploits moonlighting functions of its proteins to interfere with host cell functions. PE/PPE proteins utilize host inflammatory signaling and cell death pathways to promote pathogenesis. We report thatM. tbPE6 protein (Rv0335c) is a secretory protein effector that interacts with innate immune toll-like receptor TLR4 on the macrophage cell surface and promotes activation of the canonical NFĸB signaling pathway to stimulate secretion of proinflammatory cytokines TNF-α, IL-12, and IL-6. Using mouse macrophage TLRs knockout cell lines, we demonstrate that PE6 induced secretion of proinflammatory cytokines dependent on TLR4 and adaptor Myd88. PE6 possesses nuclear and mitochondrial targeting sequences and displayed time-dependent differential localization into nucleus/nucleolus and mitochondria, and exhibited strong Nucleolin activation. PE6 strongly induces apoptosisviaincreased production of pro-apoptotic molecules Bax, Cytochrome C, and pcMyc. Mechanistic details revealed that PE6 activates Caspases 3 and 9 and induces endoplasmic reticulum-associated unfolded protein response pathways to induce apoptosis through increased production of ATF6, Chop, BIP, eIF2α, IRE1α, and Calnexin. Despite being a potent inducer of apoptosis, PE6 suppresses innate immune defense strategy autophagy by inducing inhibitory phosphorylation of autophagy initiating kinase ULK1. Inversely, PE6 induces activatory phosphorylation of autophagy master regulator MtorC1, which is reflected by lower conversion of autophagy markers LC3BI to LC3BII and increased accumulation of autophagy substrate p62 which is also dependent on innate immune receptor TLR4. The use of pharmacological agents, rapamycin and bafilomycin A1, confirms the inhibitory effect of PE6 on autophagy, evidenced by the reduced conversion of LC3BI to LC3BII and increased accumulation of p62 in the presence of rapamycin and bafilomycin A1. We also observed that PE6 binds DNA, which could have significant implications in virulence. Furthermore, our analyses reveal that PE6 efficiently binds iron to likely aid in intracellular survival. RecombinantMycobacterium smegmatis(M. smegmatis) containingpe6displayed robust growth in iron chelated media compared to vector alone transformed cells, which suggests a role of PE6 in iron acquisition. These findings unravel novel mechanisms exploited by PE6 protein to subdue host immunity, thereby providing insights relevant to a better understanding of host–pathogen interaction duringM. tb infection.
Exploiting Single-Cell Tools in Gene and Cell Therapy
Authors: Bode Daniel , Cull Alyssa H. , Rubio-Lara Juan A. , Kent David G.
Published: July 2021

Single-cell molecular tools have been developed at an incredible pace over the last five years as sequencing costs continue to drop and numerous molecular assays have been coupled to sequencing readouts. This rapid period of technological development has facilitated the delineation of individual molecular characteristics including the genome, transcriptome, epigenome, and proteome of individual cells, leading to an unprecedented resolution of the molecular networks governing complex biological systems. The immense power of single-cell molecular screens has been particularly highlighted through work in systems where cellular heterogeneity is a key feature, such as stem cell biology, immunology, and tumor cell biology. Single-cell-omics technologies have already contributed to the identification of novel disease biomarkers, cellular subsets, therapeutic targets and diagnostics, many of which would have been undetectable by bulk sequencing approaches. More recently, efforts to integrate single-cell multi-omics with single cell functional output and/or physical location have been challenging but have led to substantial advances. Perhaps most excitingly, there are emerging opportunities to reach beyond the description of static cellular states with recent advances in modulation of cells through CRISPR technology, in particular with the development of base editors which greatly raises the prospect of cell and gene therapies. In this review, we provide a brief overview of emerging single-cell technologies and discuss current developments in integrating single-cell molecular screens and performing single-cell multi-omics for clinical applications. We also discuss how single-cell molecular assays can be usefully combined with functional data to unpick the mechanism of cellular decision-making. Finally, we reflect upon the introduction of spatial transcriptomics and proteomics, its complementary role with single-cell RNA sequencing (scRNA-seq) and potential application in cellular and gene therapy.
Geographic Variation in Bryde’s Whale Be4 Calls in the Gulf of California: An Insight to Population Dynamics
Authors: Viloria-Gómora Lorena , Urbán R Jorge , Leon-Lopez Braulio , Romero-Vivas Eduardo
Published: July 2021

Although Bryde’s whale (Balaenoptera edeni) has worldwide distribution, it is considered one of the most difficult species of baleen whales to study. Two populations existing in the Gulf of California have been proposed, but difficulties in obtaining biopsies have complicated testing the hypothesis of discrete stock difference between north and south of the Gulf. On the other hand, bioacoustics analyses have been used to differentiate populations from other whale species. Therefore, to provide information for the previously proposed hypothesis, the most common Bryde’s call (Be4) in the region was analyzed. Acoustic data was collected using a High-frequency Acoustic Recording Package (HARP) system placed at two locations in the Gulf of California: one in the north from November 2006 to June 2007 and other one in the south from August to December 2008. Duration and frequency range were measured for calls with a signal-to-noise ratio (SNR) greater than 27 dB. The Mann–Whitney-Utest was performed to compare distributions in both geographic areas, and the results were compared with a photo-identification analysis. Of the 903 Be4 calls detected, 103 (north) and 92 (south) met the SNR requirement. Duration showed a significant difference (Mann–Whitney test,U= 11238,z-statistics = 2.91,p= 0.003) with southern calls being longer than the northern ones. The results suggest that the northern population remains resident in the north with some movement toward the south, also verified by photo-identification. A detailed inspection showed a double distribution in the south (Mann–Whitney test,U= 2211,z-statistics = −8.39,p= 4.4776e-17), suggesting the presence at the same time of resident and transient populations. The latter has been suggested to belong to the Eastern Tropical Pacific. The results suggest a geographic variation inB. edeniBe4 call type and support the existence of two populations within the Gulf of California.
Crc Regulates Succinate-Mediated Repression of Mineral Phosphate Solubilization in Acinetobacter sp. SK2 by Modulating Membrane Glucose Dehydrogenase
Authors: Bharwad Krishna , Ghoghari Niharika , Rajkumar Shalini
Published: July 2021

The plant growth-promoting Acinetobacter sp. SK2 isolated from Vigna radiata rhizosphere was characterized for mineral phosphate solubilization (MPS). To understand the contribution of the membrane glucose dehydrogenase (mGDH) and soluble glucose dehydrogenase (sGDH) in glucose oxidation and MPS, insertional inactivation of the corresponding genes was carried out. The disruption of mGDH encoding gene gdhA resulted in complete loss of mGDH activity, which confirmed its role in periplasmic glucose oxidation and gluconate-mediated MPS phenotype. The inactivation of sGDH encoding gene gdhB resulted in loss of sGDH activity, which did not alter the MPS or mGDH activity. Thus, it was also concluded that the sGDH was dispensable in gluconate-mediated MPS. Supplementation of succinate in glucose-containing medium suppressed the activity of mGDH (and sGDH) and therefore repressed the MPS phenotype. The catabolite repression control protein (Crc) of Pseudomonas was implicated in Acinetobacter sp. for a similar function in the presence of preferred and non-preferred carbon sources. To understand the regulatory linkage between Crc and genes for glucose oxidation, crc mutants were generated. The inactivation of crc resulted in increased activity of the mGDH in glucose + succinate-grown cells, indicating derepression. An increase in phosphate solubilization up to 44% in glucose + succinate-grown crc– compared with glucose-grown cells was recorded, which was significantly repressed in the wild-type strain under similar conditions. It is therefore proposed that in Acinetobacter sp. SK2, Crc is involved in the succinate-provoked repression of the MPS phenotype. The gene expression data indicated that Hfq may also have a regulating role in preferential utilization of carbon source by perhaps modulating Crc–Hfq functionality. V. radiata plants inoculated with the wild type improved both root and shoot length by 1.3 to 1.4-fold. However, crc– increased the root and shoot length by 1.6-fold, compared with the uninoculated controls. In mimicking the soil condition (in the presence of multiple carbon sources, e.g., succinate along with glucose), the crc– strain of Acinetobacter sp. SK2 performed better in supporting the growth of V. radiata in pot experiments.
Detection of Hepatitis E Virus in Hyalomma lusitanicum Ticks Feeding on Wild Boars
Authors: Rivero-Juarez Antonio , Risalde María A. , Gortázar Christian , Lopez-Lopez Pedro , Barasona Jose A. , Frias Mario , Caballero-Gomez Javier , de la Fuente José , Rivero Antonio
Published: July 2021

Little is known about the role of ticks in maintaining highly prevalent zoonotic viruses in wildlife, such as hepatitis E virus (HEV), which do not require ticks for transmission between animals and humans. In this cross-sectional study, adult female ticks were collected from Eurasian wild boar (Sus scrofa) in autumn 2015 in Spain. HEV RNA in both ticks and wild boar was evaluated by RT-qPCR. Twenty-nine adult Hyalomma lusitanicum ticks were collected from 29 wild boars. HEV RNA was detected in a total of 10 tick (34.4%) and 11 wild boar serum samples (37.9%). In two cases, detectable HEV RNA was found in a wild boar but not in the tick collected from them. In contrast, one HEV-positive tick was collected from an HEV-negative wild boar. All viral sequences were consistent with genotype 3f. We describe for the first time the presence of HEV RNA in adult Hyalomma lusitanicum ticks.
“Candidatus Chlorobium masyuteum,” a Novel Photoferrotrophic Green Sulfur Bacterium Enriched From a Ferruginous Meromictic Lake
Authors: Lambrecht Nicholas , Stevenson Zackry , Sheik Cody S. , Pronschinske Matthew A. , Tong Hui , Swanner Elizabeth D.
Published: July 2021

Anoxygenic phototrophic bacteria can be important primary producers in some meromictic lakes. Green sulfur bacteria (GSB) have been detected in ferruginous lakes, with some evidence that they are photosynthesizing using Fe(II) as an electron donor (i.e., photoferrotrophy). However, some photoferrotrophic GSB can also utilize reduced sulfur compounds, complicating the interpretation of Fe-dependent photosynthetic primary productivity. An enrichment (BLA1) from meromictic ferruginous Brownie Lake, Minnesota, United States, contains an Fe(II)-oxidizing GSB and a metabolically flexible putative Fe(III)-reducing anaerobe. “CandidatusChlorobium masyuteum” grows photoautotrophically with Fe(II) and possesses the putative Fe(II) oxidase-encodingcyc2gene also known from oxygen-dependent Fe(II)-oxidizing bacteria. It lacks genes for oxidation of reduced sulfur compounds. Its genome encodes for hydrogenases and a reverse TCA cycle that may allow it to utilize H2and acetate as electron donors, an inference supported by the abundance of this organism when the enrichment was supplied by these substrates and light. The anaerobe “CandidatusPseudopelobacter ferreus” is in low abundance (∼1%) in BLA1 and is a putative Fe(III)-reducing bacterium from theGeobacteralesord. nov. While “Ca.C. masyuteum” is closely related to the photoferrotrophsC. ferroooxidansstrain KoFox andC. phaeoferrooxidansstrain KB01, it is unique at the genomic level. The main light-harvesting molecule was identified as bacteriochlorophyllcwith accessory carotenoids of the chlorobactene series. BLA1 optimally oxidizes Fe(II) at a pH of 6.8, and the rate of Fe(II) oxidation was 0.63 ± 0.069 mmol day–1, comparable to other photoferrotrophic GSB cultures or enrichments. Investigation of BLA1 expands the genetic basis for phototrophic Fe(II) oxidation by GSB and highlights the role these organisms may play in Fe(II) oxidation and carbon cycling in ferruginous lakes.
Deep Sequencing of T-Cell Receptors for Monitoring Peripheral CD8+ T Cells in Chinese Advanced Non–Small-Cell Lung Cancer Patients Treated With the Anti–PD-L1 Antibody
Authors: Sheng Jin , Wang Huadi , Liu Xiao , Deng Yunyun , Yu Yingying , Xu Pengfei , Shou Jiawei , Pan Hong , Li Hongsen , Zhou Xiaoyun , Han Weidong , Sun Tao , Pan Hongming , Fang Yong
Published: July 2021

Background: Atezolizumab, a high-affinity engineered human anti–PD-L1 antibody, has produced a clinical benefit for patients with advanced non–small-cell lung cancer (NSCLC). However, associated with T-cell regulation, the immunomodulatory effect of PD-L1 blockade and its biomarker in peripheral immunity remains elusive.

Methods: In a prospective cohort with 12 Chinese advanced NSCLC patients who received atezolizumab 1,200 mg every 3 weeks as a second-line treatment, blood samples were obtained before and 6 weeks after atezolizumab initiation, and when disease progression was confirmed. Patients were classified into a response or progression group according to response evaluation criteria in solid tumors (RECIST) 1.1. Fresh peripheral blood mononuclear cells (PBMCs) from patients were stained with antihuman CD3, CD8, and PD-1 antibodies for flow cytometry analysis. T-cell receptor (TCR)-β chains of CD8+ T cells were analyzed by next-generation sequencing (NGS) at the deep level. Diversity, clonality, and similarity of TCR have been calculated before and after treatment in both groups.

Results: Clonal expansion with high PD-1 expression was detected in all patients’ peripheral CD8+ T cells before the treatment of atezolizumab. Unlike the progression group, the diversity of TCR repertoire and singletons in the TCRβ pool increased over time with atezolizumab administration, and the TCR repertoire dynamically changes in the response group. The percentage of CD8+ PD-1high terminal exhausted T cells declined in the response group after the PD-L1 blockade. Two patterns of TCR changes among patients who received PD-L1–targeted immunotherapy were observed.

Conclusions: Deep sequencing of the T-cell receptors confirmed the existence of CD8+ PD-1high T cells with an exhaustion phenotype in Chinese NSCLC patients. Our study demonstrated that efficient anti–PD-L1 therapy could reshape the TCR repertoire for antitumor patients. Furthermore, singleton frequency may help us select patients who are sensitive to anti–PD-L1 immunotherapy.