Hit and Run oncogeneses in Head and Neck Cancers requires greater investigation

alexandrossfakianakis shared this article with you from Inoreader Hit and Run oncogeneses in Head and Neck Cancers requires greater investigation via Journal of Medical Virology Abstract Head and neck cancers are unique in so far that 2 major oncogenic viruses, EBV and HPV infect adjacent anatomy and cause nasopharyngeal and oropharyngeal cancers respectively. Dominant recognised carcinogens are alcohol and tobacco but some head and neck cancers have been found to have mixed carcinogens (including betel leaf, areca nuts, slaked lime, viruses, etc) involved in their oncogenesis and conversely, groups of patients with unknown or less dominant carcinogens involved in their development. These cancers may have had viral involvement in the past but then lost most of their viral nucleic acids (be they DNA and/or RNA) below a detection threshold, thus rendering them virus-negative. Some of these virus-negative tumours appear to have mutagenic signatures associated with virus-positive cancers i.e. from the APOBEC defence mechanism which is known to mutate viral nucleic acids as well as cause collateral damage to host DNA, with subsequent development of strongly viral prejudiced mutational signatures. These mechanisms are likely to be less efficient at oncogenesis than traditional direct EBV and HPV oncogenes driving mutagenesis, thus accounting for the smaller frequencies of these cancers found. More profound investigations of these unusual tumours are warranted to dissect out these mechanistic pathways. This article is protected by copyright. All rights reserved. View on Web

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LANA regulates miR‐155 /GATA3 signaling axis by enhancing c‐Jun/c‐Fos interaction to promote the proliferation and migration of KSHV‐infected cells

alexandrossfakianakis shared this article with you from Inoreader LANA regulates miR‐155 /GATA3 signaling axis by enhancing c‐Jun/c‐Fos interaction to promote the proliferation and migration of KSHV‐infected cells via Journal of Medical Virology Abstract Kaposi's sarcoma (KS) is the second most common tumor in people infected with human immunodeficiency virus worldwide, but its pathogenesis is still unclear. In this study, we discovered that the expression of GATA-binding protein 3 (GATA3) was lowly expressed in KS tissues and KSHV-infected cells, while microRNA-155 (miR-155) was highly expressed in KS serum and KSHV-infected cells. miR-155 promoted the proliferation, migration and invasion of KSHV infection by targeting GATA3. Further, The KSHV-encoded protein, the Latency associated nuclear antigen (LANA), promotes the proliferation, migration and invasion of KSHV-infected cells by regulating the miR-155/GATA3 axis. Regarding the molecular mechanism, c-Jun and c-Fos interact to form a complex. LANA up-regulates the expression of c-Jun and c-Fos and enhances the formation of c-Jun/c-Fos complex. The complex binds to the -95 ~ -100 bp site of miR-155 promoter and transcriptionally activates miR-155. All in a ll, LANA enhances the c-Jun/c-Fos interaction, resulting in enhanced transcriptional regulation of miR-155 by the c-Jun/c-Fos complex, thereby downregulating GATA3 and promoting the proliferation, migration and invasion of KSHV-infected cells. The discovery of LANA/c-Jun/c-Fos/miR-155/GATA3 further refines the pathogenesis of KS, potentially opening a new avenue for developing effective drugs against KS. This article is protected by copyright. All rights reserved. View on Web

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Exhaled Breath Aerosol Shedding by Highly Transmissible Versus Prior SARS-CoV-2 Variants

alexandrossfakianakis shared this article with you from Inoreader Exhaled Breath Aerosol Shedding by Highly Transmissible Versus Prior SARS-CoV-2 Variants via Clinical Infectious Diseases Advance Access Abstract Background Aerosol inhalation is recognized as the dominant mode of SARS-CoV-2 transmission. Three highly transmissible lineages evolved during the pandemic. One hypothesis to explain increased transmissibility is that natural selection favors variants with higher rates of viral aerosol shedding. However, the extent of aerosol shedding of successive SARS-CoV-2 variants is unknown. We aimed to measure the infectivity and rate of SARS-CoV-2 shedding into exhaled breath aerosol (EBA) by individuals during the Delta and Omicron waves and compared those rates with those of prior SARS-CoV-2 variants from our previously published work. Methods COVID-19 cases (n = 93, 32 vaccinated and 20 boosted) were recruited to give samples, including 30-minute breath samples into a Gesundheit-II exhaled breath aerosol sampler. Samples were quantified for viral RNA using RT-PCR and cultured for virus. Results Alpha (n = 4), Delta ( n = 3), and Omicron (n = 29) cases shed significantly more viral RNA copies into exhaled breath aerosols than cases infected with ancestral strains and variants not associated with increased transmissibility (n = 57). All Delta and Omicron cases were fully vaccinated and most Omicron cases were boosted. We cultured virus from the EBA of one boosted and three fully vaccinated cases. Conclusions Alpha, Delta, and Omicron independently evolved high viral aerosol shedding phenotypes, demonstrating convergent evolution. Vaccinated and boosted cases can shed infectious SARS-CoV-2 via EBA. These findings support a dominant role of infectious aerosols in transmission of SARS-CoV-2. Monitoring aerosol shedding from new variants and emerging pathogens can be an important component of future threat assessments and guide interventions to prevent transmission. View on Web

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The influence of apical periodontitis on circulatory inflammatory mediators in peripheral blood: a prospective case‐control study

alexandrossfakianakis shared this article with you from Inoreader The influence of apical periodontitis on circulatory inflammatory mediators in peripheral blood: a prospective case‐control study via International Endodontic Journal Abstract Aim To explore the influence of apical periodontitis (AP) on inflammatory markers in blood of otherwise healthy individuals and to depict the inflammatory profile of the healing after dental extraction. Methodology This is a prospective case-control intervention study, during which, individuals with a diagnosis of AP of one affected tooth were included, along with a control group matched for age and gender. A broad panel of blood inflammatory mediators were examined longitudinally in all subjects during 6 visits. In the case of the AP subjects, the tooth with AP was extracted at the third visit. Results were analyzed by linear regression analyses and linear mixed model analyses. Results A total of 53 subjects were included in the study, 27 with AP and 26 without. Fifteen females and 12 males were included in the AP group, and 14 females and 12 males in the control group. At baseline, G-CSF (P<0.001), IL-1β (P=0.03) and IL-4 (P=0.01) were significantly lower in AP subjects than in controls. Comparison of the differences between baseline and the last visit, i.e., three months after the tooth extraction, showed a significant reduction in IL-10 (P=0.03) and IL-12p70 (P=0.01). Conclusions The immunologic profile of chronic AP in one tooth and its healing profile reveals a systemic low-grade inflammation through compensatory immunosuppression. A larger lesion or multiple lesions could disrupt the balance that the system is trying to maintain, resulting in loss of homeostasis. View on Web

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Subgingival host‐microbiome metatranscriptomic changes following scaling and root planning in Grade II/III Periodontitis

alexandrossfakianakis shared this article with you from Inoreader Subgingival host‐microbiome metatranscriptomic changes following scaling and root planning in Grade II/III Periodontitis via Journal of Clinical Periodontology Abstract Aims To assess the effects of scaling and root planning (SRP) on the dynamics of gene expression by the host and the microbiome in subgingival plaque samples. Methods Fourteen periodontitis patients were closely monitored in the absence of periodontal treatment for 12 months. During this period, comprehensive periodontal examination and subgingival biofilm sample collection were performed bi-monthly. After 12 months, clinical attachment level (CAL) data was compiled and analyzed using linear mixed models (LMM) fitted to longitudinal CAL measurements for each tooth site. LMM classified sites as stable (S), progressing (P), or fluctuating (F). After 12 month visit, subjects received SRP and at 15 months they received comprehensive examination and supportive periodontal therapy (SPT). Those procedures were repeated at the 18 month visit, when patients were also sampled. Each patient contributed with one S, one P and one F site collected at 12 and 18 month visits. Samples were analyzed using Dual RNA-Sequencing to capture host and bacterial transcriptomes simultaneously. Results Microbiome and host response behavior were specific to the site's progression classification (i.e., S, P or F). Microbial profiles of pre and post-treatment samples exhibited specific microbiome changes, with progressing sites showing the most significant changes. Among them, P. gingivalis was reduced after treatment, while F. nucleatum showed an increase in proportion. Transcriptome analysis of the host response showed that IL-17, TNF signaling pathways, and neutrophil extracellular trap (NETs) formation were the primary immune response activities impacted by periodontal treatment. Conclusion Scaling and root planing resulted in a significant "rewiring" of host and microbial activities in the progressing sites, while in stable and fluctuating sites, the restructuring of the microbiome was minor. This article is protected by copyright. All rights reserved. View on Web

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Artificial intelligence to support early diagnosis of temporomandibular disorders: a preliminary case study

alexandrossfakianakis shared this article with you from Inoreader Artificial intelligence to support early diagnosis of temporomandibular disorders: a preliminary case study via Journal of Oral Rehabilitation Abstract Background Temporomandibular disorders (TMDs) are disabling conditions with a negative impact on the quality of life. Their diagnosis is a complex and multi-factorial process that should be conducted by experienced professionals, and most TMDs remain often undetected. Increasing the awareness of un-experienced dentists and supporting the early TMD recognition may help reduce this gap. Artificial intelligence (AI) allowing both to process natural language and to manage large knowledge bases, could support the diagnostic process. Objective In this work, we present the experience of an AI-based system for supporting non-expert dentists in early TMD recognition. Methods The system was based on commercially available AI services. The prototype development involved a preliminary domain analysis and relevant literature identification, the implementation of the core cognitive computing services, of the web interface, and preliminary testing. Performance evaluation included a retrospective review of 7 available clinical cases, together with the involvement of expert professionals for usability testing. Results The system comprises one module providing possible diagnoses according to a list of symptoms, and a second one represented by a question&answer tool, based on natural language. We found that, even when using commercial services, the training guided by experts is a key factor and that, despite the generally positive feedback, the application's best target is untrained professionals. Conclusion We provided a preliminary proof of concept of the feasibility of implementing an AI-based system aimed to support non-specialists in the early identification of TMDs, possibly allowing a faster and more frequent referral to second-level medical centers. Our results showed that AI is a useful tool to improve TMD detection by facilitating a primary diagnosis. View on Web

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Influence of genetic polymorphisms on mechanical pain sensitivity and endogenous pain modulation of trigeminal and spinal areas

alexandrossfakianakis shared this article with you from Inoreader Influence of genetic polymorphisms on mechanical pain sensitivity and endogenous pain modulation of trigeminal and spinal areas via Journal of Oral Rehabilitation Abstract Background Previous evidence indicates significant association between genetic polymorphisms and phenotypes related to pain sensitivity in patients with temporomandibular disorders (TMD). Despite the important advances in cataloging diverse factors such as sleep disorders, anxiety and depression, the interrelated mechanisms of painful TMD etiopathogenesis still need investigation. Objectives This case-control study aimed to evaluate the influence of genetic polymorphisms (rs6296, rs6295, rs1799971, rs4680, rs4633, rs4818) and psychosocial factors on the mechanical pain sensitivity and endogenous pain modulation in women with painful TMD and asymptomatic controls. Methods We evaluated six independent variables: anxiety levels, depression, stress, sleep quality, pain catastrophizing and genetic polymorphisms, and four dependent variables: mechanical pain threshold (MPT), pressure pain threshold (PPT), wind-up ratio (WUR) and conditioned pain modulation (CPM) collected at masseter (trigeminal) and hand (spinal) areas in a sample of 95 painful TMD patients and 85 controls. A regression model was used to test the possible effect of the independent variables on dependent variables. Results The regression model was significant for MPT (F11,168 = 9.772; R2=0.390). Painful TMD diagnoses and sleep quality were associated with trigeminal MPT (B coefficient = -0.499; and B coefficient = -0.211, respectively). WUR was associated with rs6295 and rs6746030 for, respectively, the spinal and trigeminal area. Conclusion Genetic polymorphisms had a slight contribution to endogenous pain modulation as indicated by the significant association with WUR but did not contribute to mechanical pain sensitivity. On the other hand, the presence of painful TMD and the sleep quality contributed significantly to mechanical pain sensitivity. View on Web

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