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Integrative transcriptome analysis reveals alternative polyadenylation potentially contributes to GCRV early infection

Front Microbiol. 2023 Nov 3;14:1269164. doi: 10.3389/fmicb.2023.1269164. eCollection 2023.

ABSTRACT

INTRODUCTION: Grass carp reovirus (GCRV), a member of the Aquareovirus genus in the Reoviridae family, is considered to be the most pathogenic aquareovirus. Productive viral infection requires extensive interactions between viruses and host cells. However, the molecular mechanisms underlying GCRV early infection remains elusive.

METHODS: In this study we performed transcriptome and DNA methylome analyses with Ctenopharyngodon idellus kidney (CIK) cells infected with GCRV at 0, 4, and 8 h post infection (hpi), respectively.

RESULTS: We found that at early infection stage the differentially expressed genes related to defense response and immune response in CIK cells are activated. Although DNA methylation pattern of CIK cells 8 hpi is similar to mock-infected cells, we identified a considerable number of genes that selectively utilize alternative polyadenylation sites. Particularly, we found that biological processes of cytoskeleton organization and regulation of microtubule polymerization are statistically enriched in the genes with altered 3’UTRs.

DISCUSSION: Our results suggest that alternative polyadenylation potentially contributes to GCRV early infection.

PMID:38029205 | PMC:PMC10656684 | DOI:10.3389/fmicb.2023.1269164

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Genotype characterization of Epstein-Barr virus among adults living with human immunodeficiency virus in Ethiopia

Front Microbiol. 2023 Oct 31;14:1270824. doi: 10.3389/fmicb.2023.1270824. eCollection 2023.

ABSTRACT

BACKGROUND: Epstein-Barr virus (EBV) is a human lymphotropic herpesvirus with a causative agent in cancer. There are two genotypes of EBV (EBV genotype 1 and EBV genotype 2) that have been shown to infect humans. This study aimed to characterize the EBV genotype among people with human immunodeficiency virus (PWH) and HIV-negative individuals in Ethiopia.

METHODS: DNA was extracted from peripheral blood mononuclear cells (PBMCs). Conventional polymerase chain reaction (cPCR) targeting EBNA3C genes was performed for genotyping. A quantitative real-time PCR (q-PCR) assay for EBV DNA (EBNA1 ORF) detection and viral load quantification was performed. Statistical significance was determined at a value of p < 0.05.

RESULT: In this study, 155 EBV-seropositive individuals were enrolled, including 128 PWH and 27 HIV-negative individuals. Among PWH, EBV genotype 1 was the most prevalent (105/128, 82.0%) genotype, followed by EBV genotype 2 (17/128, 13.3%), and mixed infection (6/128, 4.7%). In PWH, the median log10 of EBV viral load was 4.23 copies/ml [interquartile range (IQR): 3.76-4.46], whereas it was 3.84 copies/ml (IQR: 3.74-4.02) in the HIV-negative group. The EBV viral load in PWH was significantly higher than that in HIV-negative individuals (value of p = 0.004). In PWH, the median log10 of EBV viral load was 4.25 copies/ml (IQR: 3.83-4.47) in EBV genotype 1 and higher than EBV genotype 2 and mixed infection (p = 0.032).

CONCLUSION: In Ethiopia, EBV genotype 1 was found to be the most predominant genotype, followed by EBV genotype 2. Understanding the genotype characterization of EBV in PWH is essential for developing new and innovative strategies for preventing and treating EBV-related complications in this population.

PMID:38029140 | PMC:PMC10644458 | DOI:10.3389/fmicb.2023.1270824

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Genetic causal relationship between gut microbiome and psoriatic arthritis: a bidirectional two-sample Mendelian randomization study

Front Microbiol. 2023 Oct 31;14:1265786. doi: 10.3389/fmicb.2023.1265786. eCollection 2023.

ABSTRACT

BACKGROUND: Several observational studies have suggested a potential relationship between gut microbiome and psoriatic arthritis (PsA). However, the causality of this relationship still remains unclear. We aim to explore if the specific gut microbiome is causally associated with PsA at the genetic level and offer valuable insights into the etiology of PsA.

METHODS: In this study, we employed a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal effects of the gut microbiome on PsA. Publicly accessible genome-wide association study summary data of gut microbiome were obtained from the MiBioGen consortium (n = 14,306), while the summary statistics of psoriatic arthropathies were sourced from the FinnGen consortium R8 release data (2,776 cases and 221,323 controls). The primary analytical method employed was inverse variance weighted (IVW), complemented by supplementary methods including MR-Egger, weighted median, weighted mode, maximum likelihood, MR-PRESSO, and cML-MA. Reverse MR analysis was performed on the bacteria that were found to be causally associated with PsA in forward MR analysis. Cochran’s IVW Q statistic was utilized to assess the heterogeneity of instrumental variables among the selected single nucleotide polymorphisms.

RESULTS: IVW estimates revealed that Ruminococcaceae_UCG-002 (odds ratio (OR) = 0.792, 95% confidence interval (CI), 0.643-0.977, p = 0.029) exhibited a protective effect on PsA. Conversely, Blautia (OR = 1.362, 95% CI, 1.008-1.842, p = 0.044), Eubacterium_fissicatena_group (OR = 1.28, 95% CI, 1.075-1.524, p = 0.006), and Methanobrevibacter (OR = 1.31, 95% CI, 1.059-1.621, p = 0.013) showed a positive correlation with the risk of PsA. No significant heterogeneity, horizontal pleiotropy, or outliers were observed, and the results of the MR analysis remained unaffected by any single nucleotide polymorphisms. According to the results of reverse MR analysis, no significant causal effect of PsA was found on gut microbiome.

CONCLUSION: This study establishes for the first time a causal relationship between the gut microbiome and PsA, providing potential valuable strategies for the prevention and treatment of PsA. Further randomized controlled trials are urgently warranted to support the targeted protective mechanisms of probiotics on PsA.

PMID:38029137 | PMC:PMC10644104 | DOI:10.3389/fmicb.2023.1265786

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Metabolomic profiling of Marek’s disease virus infection in host cell based on untargeted LC-MS

Front Microbiol. 2023 Nov 9;14:1270762. doi: 10.3389/fmicb.2023.1270762. eCollection 2023.

ABSTRACT

Marek’s disease (MD) caused by Marek’s disease virus (MDV), poses a serious threat to the poultry industry by inducing neurological disease and malignant lymphoma in infected chickens. However, the underlying mechanisms how MDV disrupts host cells and causes damage still remain elusive. Recently, the application of metabolomics has shown great potential for uncovering the complex mechanisms during virus-host interactions. In this study, chicken embryo fibroblasts (CEFs) infected with MDV were subjected to ultrahigh-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS) and multivariate statistical analysis. The results showed that 261 metabolites were significantly altered upon MDV infection, with most changes occurring in amino acid metabolism, energy metabolism, nucleotide metabolism, and lipid metabolism. Notably, MDV infection induces an up-regulation of amino acids in host cells during the early stages of infection to provide the energy and intermediary metabolites necessary for efficient multiplication of its own replication. Taken together, these data not only hold promise in identifying the biochemical molecules utilized by MDV replication in host cells, but also provides a new insight into understanding MDV-host interactions.

PMID:38029131 | PMC:PMC10666056 | DOI:10.3389/fmicb.2023.1270762

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The analysis of Lactobacillus spp. distribution in the vaginal microbiota of Polish women with abnormal Pap smear result

Front Microbiol. 2023 Nov 9;14:1257587. doi: 10.3389/fmicb.2023.1257587. eCollection 2023.

ABSTRACT

INTRODUCTION: A healthy vaginal microbiota is represented mainly by Lactobacillus spp. and plays a vital role in maintaining the functional balance in the vaginal environment. Scientists have drawn attention to possible correlations between the vaginal microbiome and gynecological neoplasms. Several recent studies have shown a potential link between the vaginal microbiome and the risk of developing cervical cancer from human papillomavirus (HPV) infection. This study aimed to compare the prevalence and abundance of various lactic acid bacteria species (LABs) in vaginal swabs from healthy controls and patients with abnormal Pap smear results.

METHODS: The study included 100 women (79 patients with abnormal cervical Pap smear results and 21 controls) from whom vaginal swabs were collected. Real-time quantitative PCR was used to determine seven lactic acid bacteria (LAB) species and their quantities.

RESULTS: Most patients were colonized by two Lactobacillus species, primarily Lactobacillus gasseri (93%) and L. crispatus (83%). Patient age and place of residence were associated with the diversity of LAB in the vaginal microbiota. The abundance of L. delbrueckii in the vaginal microbiota increased, whereas the abundance of L. gasseri abundance decreased, with patient age. Lactobacillus acidophilus and Limosilactobacillus fermentum were significantly more often detected in patients living in rural versus urban areas. Statistical analysis did not show any significant differences in LAB between groups of patients with various changes on smear tests.

DISCUSSION: The degree of dysplastic changes in the endothelium or the presence of a group of atypical cervical stratified epithelial cells was not associated with significant changes in the studied vaginal bacteria.

PMID:38029074 | PMC:PMC10666048 | DOI:10.3389/fmicb.2023.1257587

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How do you make a robot smarter? Program it to know what it doesn’t know

Engineers have come up with a new way to teach robots to know when they don’t know. The technique involves quantifying the fuzziness of human language and using that measurement to tell robots when to ask for further directions. Telling a robot to pick up a bowl from a table with only one bowl is fairly clear. But telling a robot to pick up a bowl when there are five bowls on the table generates a much higher degree of uncertainty — and triggers the robot to ask for clarification.
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Nevin Manimala Statistics

Incivility in COVID-19 Vaccine Mandate Discourse and Moral Foundations: Natural Language Processing Approach

JMIR Form Res. 2023 Nov 29;7:e50367. doi: 10.2196/50367.

ABSTRACT

BACKGROUND: Vaccine hesitancy poses a substantial threat to efforts to mitigate the harmful effects of the COVID-19 pandemic. To combat vaccine hesitancy, officials in the United States issued vaccine mandates, which were met with strong antivaccine discourse on social media platforms such as Reddit. The politicized and polarized nature of COVID-19 on social media has fueled uncivil discourse related to vaccine mandates, which is known to decrease confidence in COVID-19 vaccines.

OBJECTIVE: This study examines the moral foundations underlying uncivil COVID-19 vaccine discourse. Moral foundations theory poses that individuals make decisions to express approval or disapproval (ie, uncivil discourse) based on innate moral values. We examine whether moral foundations are associated with dimensions of incivility. Further, we explore whether there are any differences in the presence of incivility between the r/coronaviruscirclejerk and r/lockdownskepticism subreddits.

METHODS: Natural language processing methodologies were leveraged to analyze the moral foundations underlying uncivil discourse in 2 prominent antivaccine subreddits, r/coronaviruscirclejerk and r/lockdownskepticism. All posts and comments from both of the subreddits were collected since their inception in March 2022. This was followed by filtering the data set for key terms associated with the COVID-19 vaccine (eg, “vaccinate” and “Pfizer”) and mandates (eg, “forced” and “mandating”). These key terms were selected based on a review of existing literature and because of their salience in both of the subreddits. A 10% sample of the filtered key terms was used for the final analysis.

RESULTS: Findings suggested that moral foundations play a role in the psychological processes underlying uncivil vaccine mandate discourse. Specifically, we found substantial associations between all moral foundations (ie, care and harm, fairness and cheating, loyalty and betrayal, authority and subversion, and sanctity and degradation) and dimensions of incivility (ie, toxicity, insults, profanity, threat, and identity attack) except for the authority foundation. We also found statistically significant differences between r/coronaviruscirclejerk and r/lockdownskepticism for the presence of the dimensions of incivility. Specifically, the mean of identity attack, insult, toxicity, profanity, and threat in the r/lockdownskepticism subreddit was significantly lower than that in the r/coronaviruscirclejerk subreddit (P<.001).

CONCLUSIONS: This study shows that moral foundations may play a substantial role in the presence of incivility in vaccine discourse. On the basis of the findings of the study, public health practitioners should tailor messaging by addressing the moral values underlying the concerns people may have about vaccines, which could manifest as uncivil discourse. Another way to tailor public health messaging could be to direct it to parts of social media platforms with increased uncivil discourse. By integrating moral foundations, public health messaging may increase compliance and promote civil discourse surrounding COVID-19.

PMID:38019581 | DOI:10.2196/50367

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Effects of an Individualized mHealth-Based Intervention on Health Behavior Change and Cardiovascular Risk Among People With Metabolic Syndrome Based on the Behavior Change Wheel: Quasi-Experimental Study

J Med Internet Res. 2023 Nov 29;25:e49257. doi: 10.2196/49257.

ABSTRACT

BACKGROUND: Metabolic syndrome (MetS) is a common public health challenge. Health-promoting behaviors such as diet and physical activity are central to preventing and controlling MetS. However, the adoption of diet and physical activity behaviors has always been challenging. An individualized mobile health (mHealth)-based intervention using the Behavior Change Wheel is promising in promoting health behavior change and reducing atherosclerotic cardiovascular disease (ASCVD) risk. However, the effects of this intervention are not well understood among people with MetS in mainland China.

OBJECTIVE: We aimed to evaluate the effects of the individualized mHealth-based intervention using the Behavior Change Wheel on behavior change and ASCVD risk in people with MetS.

METHODS: We conducted a quasi-experimental, nonrandomized study. Individuals with MetS were recruited from the health promotion center of a tertiary hospital in Zhejiang province, China. The study involved 138 adults with MetS, comprising a control group of 69 participants and an intervention group of 69 participants. All participants received health education regarding diet and physical activity. The intervention group additionally received a 12-week individualized intervention through a WeChat mini program and a telephone follow-up in the sixth week of the intervention. Primary outcomes included diet, physical activity behaviors, and ASCVD risk. Secondary outcomes included diet self-efficacy, physical activity self-efficacy, knowledge of MetS, quality of life, and the quality and efficiency of health management services. The Mann-Whitney U test and Wilcoxon signed rank test were primarily used for data analysis. Data analysis was conducted based on the intention-to-treat principle using SPSS (version 25.0; IBM Corp).

RESULTS: Baseline characteristics did not differ between the 2 groups. Compared with the control group, participants in the intervention group showed statistically significant improvements in diet behavior, physical activity behavior, diet self-efficacy, physical activity self-efficacy, knowledge of MetS, physical health, and mental health after a 12-week intervention (P=.04, P=.001, P=.04, P=.04, P=.001, P=.04, P=.04, and P<.05). The intervention group demonstrated a statistically significant improvement in outcomes from pre- to postintervention evaluations (P<.001, P=.03, P<.001, P=.04, P<.001, P<.001, and P<.001). The intervention also led to enhanced health management services and quality.

CONCLUSIONS: The individualized mHealth-based intervention using the Behavior Change Wheel was effective in promoting diet and physical activity behaviors in patients with MetS. Nurses and other health care professionals may incorporate the intervention into their health promotion programs.

PMID:38019579 | DOI:10.2196/49257

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Consideration of Sex, Gender, or Age on Outcomes of Digital Technologies for Treatment and Monitoring of Chronic Obstructive Pulmonary Disease: Overview of Systematic Reviews

J Med Internet Res. 2023 Nov 29;25:e49639. doi: 10.2196/49639.

ABSTRACT

BACKGROUND: Several systematic reviews have addressed digital technology use for treatment and monitoring of chronic obstructive pulmonary disease (COPD).

OBJECTIVE: This study aimed to assess if systematic reviews considered the effects of sex, gender, or age on the outcomes of digital technologies for treatment and monitoring of COPD through an overview of such systematic reviews. The objectives of this overview were to (1) describe the definitions of sex or gender used in reviews; (2) determine whether the consideration of sex, gender, or age was planned in reviews; (3) determine whether sex, gender, or age was reported in review results; (4) determine whether sex, gender, or age was incorporated in implications for clinical practice in reviews; and (5) create an evidence map for development of individualized clinical recommendations for COPD based on sex, gender, or age diversity.

METHODS: MEDLINE, the Cochrane Library, Epistemonikos, Web of Science, and the bibliographies of the included systematic reviews were searched to June 2022. Inclusion was based on the PICOS framework: (1) population (COPD), (2) intervention (any digital technology), (3) comparison (any), (4) outcome (any), and (5) study type (systematic review). Studies were independently selected by 2 authors based on title and abstract and full-text screening. Data were extracted by 1 author and checked by another author. Data items included systematic review characteristics; PICOS criteria; and variables related to sex, gender, or age. Systematic reviews were appraised using A Measurement Tool to Assess Systematic Reviews, version 2 (AMSTAR 2). Data were synthesized using descriptive statistics.

RESULTS: Of 1439 records, 30 systematic reviews published between 2010 and 2022 were included in this overview. The confidence in the results of 25 of the 30 (83%) reviews was critically low according to AMSTAR 2. The reviews focused on user outcomes that potentially depend on sex, gender, or age, such as efficacy or effectiveness (25/30, 83%) and acceptance, satisfaction, or adherence (3/30, 10%) to digital technologies for COPD. Reviews reported sex or gender (19/30 systematic reviews) or age (25/30 systematic reviews) among primary study characteristics. However, only 1 of 30 reviews included age in a subgroup analysis, and 3 of 30 reviews identified the effects of sex, gender, or age as evidence gaps.

CONCLUSIONS: This overview shows that the effects of sex, gender, or age were rarely considered in 30 systematic reviews of digital technologies for COPD treatment and monitoring. Furthermore, systematic reviews did not incorporate sex, gender, nor age in their implications for clinical practice. We recommend that future systematic reviews should (1) evaluate the effects of sex, gender, or age on the outcomes of digital technologies for treatment and monitoring of COPD and (2) better adhere to reporting guidelines to improve the confidence in review results.

TRIAL REGISTRATION: PROSPERO CRD42022322924; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=322924.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/40538.

PMID:38019578 | DOI:10.2196/49639

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Risk of Suicide and Psychiatric Disorders Among Isotretinoin Users: A Meta-Analysis

JAMA Dermatol. 2023 Nov 29. doi: 10.1001/jamadermatol.2023.4579. Online ahead of print.

ABSTRACT

IMPORTANCE: Isotretinoin is hypothesized to contribute to the development of psychiatric disorders, but the epidemiological association and risk factors associated with psychiatric disorders among isotretinoin users remain unclear.

OBJECTIVE: To clarify the absolute and relative risk and risk factors associated with suicide and psychiatric disorders among isotretinoin users.

DATA SOURCES: PubMed, Embase, Web of Science, and Scopus were searched from inception until January 24, 2023.

STUDY SELECTION: Randomized trials and observational studies were selected if they reported the absolute risk, relative risk, and risk factors for suicide and psychiatric disorders among isotretinoin users.

DATA EXTRACTION AND SYNTHESIS: Relevant data were extracted and risk of bias was evaluated at the study level using the Newcastle-Ottawa Scale. Data were pooled using inverse variance-weighted meta-analyses. Heterogeneity was measured using the I2 statistic, and meta-regression analyses were performed.

MAIN OUTCOMES AND MEASURES: Absolute risk (percentage), relative risks (risk ratios [RR]), and risk factors (RR) of suicide and psychiatric disorders among isotretinoin users.

RESULTS: A total of 25 studies including 1 625 891 participants were included in the review and 24 in the meta-analysis. Among the included studies, participants’ average age ranged from 16 to 38 years, and distribution by sex ranged from 0% to 100% male. The 1-year pooled absolute risk from between 2 and 8 studies of completed suicide, suicide attempt, suicide ideation, and self-harm were each less than 0.5%, while that of depression was 3.83% (95% CI, 2.45-5.93; I2 = 77%) in 11 studies. Isotretinoin users were less likely than nonusers to attempt suicide at 2 years (RR, 0.92; 95% CI, 0.84-1.00; I2 = 0%), 3 years (RR, 0.86; 95% CI, 0.77-0.95; I2 = 0%), and 4 years (RR, 0.85; 95% CI, 0.72-1.00; I2 = 23%) following treatment. Isotretinoin was not associated with the risk of all psychiatric disorders (RR, 1.08; 95% CI, 0.99-1.19; I2 = 0%). Study-level meta-regression found that studies with participants of older age reported lower 1-year absolute risk of depression, while those with a higher percentage of male participants reported a higher 1-year absolute risk of completed suicide.

CONCLUSIONS AND RELEVANCE: The findings suggest that at a population level, isotretinoin users do not have increased risk of suicide or psychiatric conditions but may instead have a lower risk of suicide attempts at 2 to 4 years following treatment. While these findings are reassuring, clinicians should continue to practice holistic psychodermatologic care and monitor patients for signs of mental distress during isotretinoin treatment.

PMID:38019562 | DOI:10.1001/jamadermatol.2023.4579