Establishment of a diverse head and neck squamous cancer cell bank using conditional reprogramming culture methods

alexandrossfakianakis shared this article with you from Inoreader Establishment of a diverse head and neck squamous cancer cell bank using conditional reprogramming culture methods via Journal of Medical Virology Abstract Most laboratory models of head and neck squamous cell cancer (HNSCC) rely on established immortalized cell lines, which carry inherent bias due to selection and clonality. We established a robust panel of HNSCC tumor cultures using a "conditional reprogramming" (CR) method, which utilizes a rho kinase inhibitor (Y-27632) and co-culture with irradiated fibroblast (J2 strain) feeder cells to support indefinite tumor cell survival. Sixteen CR cultures were successfully generated from 19 consecutively enrolled ethnically and racially diverse patients with HNSCC at a tertiary care center in the Bronx, NY. Of the 16 CR cultures, 9/16 were derived from oral cavity, 4/16 were derived from oropharynx, and 3/16 were from laryngeal carcinomas. Short tandem repeat (STR) profiling was used to validate culture against patient tumor tissue DNA. All CR cultures expressed ΔNp63 and cytokeratin 5/6, which are markers of squamous identity. Human papilloma virus (HPV) testing was assessed utiliz ing clinical p16 staining on primary tumors, RT-PCR of HPV16/18 specific viral oncogenes E6 and E7 in RNA extracted from tumor samples, and HPV DNA sequencing. Three of 4 oropharyngeal tumors were p16 and HPV-positive and maintained HPV in culture. CR cultures were able to establish three-dimensional spheroid and murine flank and orthotopic tongue models. CR methods can be readily applied to all HNSCC tumors regardless of patient characteristics, disease site, and molecular background, providing a translational research model that properly includes patient and tumor diversity. This article is protected by copyright. All rights reserved. View on Web

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Avian influenza A virus H7N9 in China, a role reversal from reassortment receptor to the donator

alexandrossfakianakis shared this article with you from Inoreader Avian influenza A virus H7N9 in China, a role reversal from reassortment receptor to the donator via Journal of Medical Virology Abstract Reassortment can introduce one or more gene segments of influenza A viruses (IAVs) into another, resulting in novel subtypes. Since 2013, a new outbreak of human highly pathogenic avian influenza has emerged in the Yangtze River Delta (YRD) and South-Central regions of China. In this study, using Anhui province as an example, we discuss the possible impact of H7N9 IAVs on future influenza epidemics through a series of gene reassortment events. Sixty-one human H7N9 isolates were obtained from five outbreaks in Anhui province from 2013–2019. Bioinformatics analyses revealed that all of them were characterized by low pathogenicity and high human or mammalian tropism and have introduced novel avian influenza A virus (AIV) subtypes such as H7N2, H7N6, H9N9, H5N6, H6N6, and H10N6 through gene reassortment. In reassortment events, Anhui isolates may donate one or more segments of HA, NA, and the six internal protein-coding genes for the novel subtype AIVs. Our study revealed that H7N9, H9N2, and H5N1 can serve as stable and persistent gene pools for AIVs in the YRD and South-Central regions of China. Novel AIV subtypes might be generated continuously by reassortment. These AIVs may have obtained human-type receptor-binding abilities from their donors and prefer binding to them, which can cause human epidemics through accidental spillover infections. Facing the continual threat of emerging avian influenza, constant monitoring of AIVs should be conducted closely for agricultural and public health. This article is protected by copyright. All rights reserved. View on Web

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Gimap5 promoted RSV degradation through interaction with M6PR

alexandrossfakianakis shared this article with you from Inoreader Gimap5 promoted RSV degradation through interaction with M6PR via Journal of Medical Virology Abstract Backgroud Respiratory Syncytial Virus (RSV) is one of the main pathogens of viral pneumonia and bronchiolitis in infants and young children and a life threatening diseases among infants and young children. GTPases of the immune-associated protein family (GIMAP) are a new family members of immune-associated GTPases. In recent years, much attention has been paid to the function of the GIMAP family in coping with infection and stress. Gimap5 is a member of the GIMAP family, which may be correlated with anti-infectious immunity. Methods RT-qPCR, Western blot and indirect immunofluorescence (IFA) were used to detect the expression of Gimap5, M6PR and IGF1R(the major RSV receptor). Transmission electron microscopy (TEM) was used to detect the degradation of RSV in Gimap5-overexpressed or -silent cell lines. Computer virtual screening was used to screen small molecule compounds targeting Gimap5 and the anti-RSV effects were explored through in vivo and in vitro experiments. Results GIMAP5 and M6PR were significantly down-regulated after RSV infection. Gimap5 accelerated RSV degradation in lysosomes by interacting with M6PR, and further prevented RSV invasion by down-regulating the expression of RSV surface receptor IGF1R. Three small molecule compounds targeting Gimap5 were confirmed to be the agonists of Gimap5. The three compounds effectively inhibited RSV infection and RSV-induced complications. Conclusion Gimap5 promotes the degradation of RSV and its receptor through interacting with M6PR. Gimap5 agonists can effectively reduce RSV infection and RSV-induced complication in vivo and in vitro, which provides a new choice for the treatment of RSV. This article is protected by copyright. All rights reserved. View on Web

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Evaluation the efficacy and safety of N‐acetylcysteine inhalation spray in controlling the symptoms of patients with COVID‐19: An open‐label randomized controlled clinical trial

alexandrossfakianakis shared this article with you from Inoreader Evaluation the efficacy and safety of N‐acetylcysteine inhalation spray in controlling the symptoms of patients with COVID‐19: An open‐label randomized controlled clinical trial via Journal of Medical Virology Abstract Background The aim of this study was to evaluate the effect and safety of N-acetylcysteine (NAC) inhalation spray in the treatment of patients with coronavirus disease 2019 (COVID-19). Methods This randomized controlled clinical trial study was conducted on patients with COVID-19. Eligible patients (n=250) were randomly allocated into the intervention group (routine treatment + NAC inhaler spray one puff per 12 hours, for 7 days) or the control group who received routine treatment alone. Clinical features, hemodynamic, hematological, biochemical parameters and patient outcomes were assessed and compared before and after treatment. Results The mortality rate was significantly higher in the control group than in the intervention group (39.2% vs 3.2%, P<0.001). Significant differences were found between the two groups (intervention and control, respectively) for white blood cell count (6.2 vs 7.8, P<0.001), hemoglobin (12.3 vs 13.3, P=0.002), C-reactive protein (CRP: 6 vs 11.5, P<0.0001) and aspartate aminotransferase (AST: 32 vs 25.5, P<0.0001). No differences were seen for hospital length of stay (11.98±3.61 vs 11.81±3.52, P=0.814) or the requirement for ICU admission (7.2% vs 11.2%, P=0.274). Conclusions NAC was beneficial in reducing the mortality rate in patients with COVID-19 and inflammatory parameters, and a reduction in the development of severe respiratory failure; however, it did not affect the length of hospital stay or the need for ICU admission. Data on the effectiveness of NAC for SARS-CoV-2 is limited and further research is required. Clinical Trial Registration This study Registered at Iranian Registry of Clinical Trials (IRCT20080901001165N55) dated 23-05-2020. This article is protected by copyright. All rights reserved. View on Web

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Mendelian randomization suggests a potential causal effect of eosinophil count on influenza vaccination responsiveness

alexandrossfakianakis shared this article with you from Inoreader Mendelian randomization suggests a potential causal effect of eosinophil count on influenza vaccination responsiveness via Journal of Medical Virology Abstract Currently, the clinical factors affecting immune responses to influenza vaccines have not been systematically explored. The mechanism of low responsiveness to influenza vaccination (LRIV) is complicated and not thoroughly elucidated. Thus, we integrate our in-house genome-wide association studies (GWAS) analysis result of LRIV (N = 111, Ncase [Low Responders] = 34, Ncontrol [Responders] = 77) with the GWAS summary of 10 blood-based biomarkers (sample size ranging from 62,076 to 108,794) deposited in BioBank Japan (BBJ) to comprehensively explore the shared genetics between LRIV and blood-based biomarkers to investigate the causal relationships between blood-based biomarkers and LRIV by Mendelian randomization (MR). The applications of four MR approaches (inverse-variance-weighted (IVW), weighted median, weighted mode, and generalized summary-data-based Mendelian randomization (GSMR)) suggested that the genetically instrumented LRIV was associated with decreased eosinophil count (� � = -5.517 to -4.422, p-value = 0.004 to 0.039). Finally, we conclude that the low level of eosinophil count is a suggestive risk factor for LRIV. This article is protected by copyright. All rights reserved. View on Web

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The prognostic significance of hematogones in childhood B‐cell acute lymphoblastic leukemia

alexandrossfakianakis shared this article with you from Inoreader The prognostic significance of hematogones in childhood B‐cell acute lymphoblastic leukemia via Pediatric Blood & Cancer Abstract Background Recent studies have demonstrated hematogones (HGs) expansion to be associated with favorable outcomes in hematological diseases, especially in patients with acute myeloid leukemia and patients undergoing hematopoietic stem cell transplantation. Acute lymphoblastic leukemia (ALL) is the most common form of cancer in children. As of now, minimal residual disease (MRD) remains the most compelling independent prognostic factor in childhood ALL. There is need for more prognostic tools for evaluating relapse risk. Procedure The goal of this study was to assess the prognostic value of HGs on relapse-free survival (RFS) and overall survival (OS) in childhood ALL. In this prospective cohort study, a total of 122 subjects with definitive diagnosis of precursor B lymphoblastic leukemia were evaluated. Flow cytometric HG detection was performed in bone marrow aspirates after induction and consolidation therapy. Results The median follow-up period of patients was 35.5 ± 9.4 (SD) months. Patients who had at least 1.0% HGs had a significantly better RFS (p = .023). Moreover, univariate and multivariate analyses confirmed that positive HGs were independently associated with longer RFS (unadjusted model: hazard ratio = 0.33, 95% CI = 0.12–0.91, p = .031; adjusted model: hazard ratio = 0.30, 95% CI = 0.11–0.82, p = .020). Conclusions Along with the role of MRD, our study shows the significance of HGs as an independent prognostic factor. The results indicate the independent prognostic value of HGs on RFS after adjustment for other prognostic factors, and can be beneficial for risk stratification and treatment modifications amongst pediatric B-cell ALL patients. View on Web

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Duration of antibiotic treatment for acute graft pyelonephritis: What's the standard of care?

alexandrossfakianakis shared this article with you from Inoreader Duration of antibiotic treatment for acute graft pyelonephritis: What's the standard of care? via Transplant Infectious Disease Abstract Background Limited evidence is available to inform the duration of antibiotic treatment in kidney transplant recipients with bacterial acute graft pyelonephritis. Guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation suggest a 14–21 day duration. Methods A four-question survey was constructed to determine the current standard of practice for the duration of treatment for acute graft pyelonephritis. The survey was distributed among members of the Infectious Diseases and the Kidney Pancreas Communities of Practice of the American Society of Transplantation. Results Among 144 survey respondents, 87 (60%) were infectious disease physicians, and 36 (25%) were transplant nephrologists. Although most (55%) respondents preferred a 14-day duration, a spread between 7 and 28 days was observed. Goals of treatment and drivers for longer duration differed between infectious disease physicians and transplant nephrologists. Conclusions Although most respondents prefer a 14-day duration of treatment for acute graft pyelonephritis, a wide range of responses was seen between 7 and 28 days. More evidence is needed to inform optimal treatment duration in this common infectious complication after transplantation. View on Web

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