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Nobendu Mukerjee, Swastika Maitra, Sukhamoy Gorai, Arabinda Ghosh, Athanasiosis Alexiou, Nanasaheb D. Thorat
Journal of Medical Virology, 5.10.2023
Tilføjet 5.10.2023
Jesper D. Gunst, Jesper F. Højen, Marie H. Pahus, Miriam Rosás-Umbert, Birgitte Stiksrud, James H. McMahon, Paul W. Denton, Henrik Nielsen, Isik S. Johansen, Thomas Benfield, Steffen Leth, Jan Gerstoft, Lars Østergaard, Mariane H. Schleimann, Rikke Olesen, Henrik Støvring, Line Vibholm, Nina Weis, Anne M. Dyrhol-Riise, Karen B. H. Pedersen, Jillian S. Y. Lau, Dennis C. Copertino Jr, Noemi Linden, Tan T. Huynh, Victor Ramos, R. Brad Jones, Sharon R. Lewin, Martin Tolstrup, Thomas A. Rasmussen, Michel C. Nussenzweig, Marina Caskey, Dag Henrik Reikvam, Ole S. Søgaard
Nature, 12.09.2023
Tilføjet 12.09.2023
Tara K. Sigdel, Patrick Boada, Maggie Kerwin, Priyanka Rashmi, David Gjertson, Maura Rossetti, Swastika Sur, Dane Munar, James Cimino, Richard Ahn, Harry Pickering, Subha Sen, Rajesh Parmar, Benoit Fatou, Hanno Steen, Joanna Schaenman, Suphamai Bunnapradist, Elaine F. Reed, Minnie M. Sarwal, CMV Systems Immunobiology Group
PLoS One Infectious Diseases, 20.05.2023
Tilføjet 20.05.2023
by Tara K. Sigdel, Patrick Boada, Maggie Kerwin, Priyanka Rashmi, David Gjertson, Maura Rossetti, Swastika Sur, Dane Munar, James Cimino, Richard Ahn, Harry Pickering, Subha Sen, Rajesh Parmar, Benoit Fatou, Hanno Steen, Joanna Schaenman, Suphamai Bunnapradist, Elaine F. Reed, Minnie M. Sarwal, CMV Systems Immunobiology Group Background Cytomegalovirus (CMV) infection, either de novo or as reactivation after allotransplantation and chronic immunosuppression, is recognized to cause detrimental alloimmune effects, inclusive of higher susceptibility to graft rejection and substantive impact on chronic graft injury and reduced transplant survival. To obtain further insights into the evolution and pathogenesis of CMV infection in an immunocompromised host we evaluated changes in the circulating host proteome serially, before and after transplantation, and during and after CMV DNA replication (DNAemia), as measured by quantitative polymerase chain reaction (QPCR). Methods LC-MS-based proteomics was conducted on 168 serially banked plasma samples, from 62 propensity score-matched kidney transplant recipients. Patients were stratified by CMV replication status into 31 with CMV DNAemia and 31 without CMV DNAemia. Patients had blood samples drawn at protocol times of 3- and 12-months post-transplant. Additionally, blood samples were also drawn before and 1 week and 1 month after detection of CMV DNAemia. Plasma proteins were analyzed using an LCMS 8060 triple quadrupole mass spectrometer. Further, public transcriptomic data on time matched PBMCs samples from the same patients was utilized to evaluate integrative pathways. Data analysis was conducted using R and Limma. Results Samples were segregated based on their proteomic profiles with respect to their CMV Dnaemia status. A subset of 17 plasma proteins was observed to predict the onset of CMV at 3 months post-transplant enriching platelet degranulation (FDR, 4.83E-06), acute inflammatory response (FDR, 0.0018), blood coagulation (FDR, 0.0018) pathways. An increase in many immune complex proteins were observed at CMV infection. Prior to DNAemia the plasma proteome showed changes in the anti-inflammatory adipokine vaspin (SERPINA12), copper binding protein ceruloplasmin (CP), complement activation (FDR = 0.03), and proteins enriched in the humoral (FDR = 0.01) and innate immune responses (FDR = 0.01). Conclusion Plasma proteomic and transcriptional perturbations impacting humoral and innate immune pathways are observed during CMV infection and provide biomarkers for CMV disease prediction and resolution. Further studies to understand the clinical impact of these pathways can help in the formulation of different types and duration of anti-viral therapies for the management of CMV infection in the immunocompromised host.
Læs mere Tjek på PubMedDanish M. Anwer, Francesco Gubinelli, Yunus A. Kurt, Livija Sarauskyte, Febe Jacobs, Chiara Venuti, Ivette M. Sandoval, Yiyi Yang, Jennifer Stancati, Martina Mazzocchi, Edoardo Brandi, Gerard O’Keeffe, Kathy Steece-Collier, Jia-Yi Li, Tomas Deierborg, Fredric P. Manfredsson, Marcus Davidsson, Andreas Heuer
PLoS One Infectious Diseases, 2.05.2023
Tilføjet 2.05.2023
by Danish M. Anwer, Francesco Gubinelli, Yunus A. Kurt, Livija Sarauskyte, Febe Jacobs, Chiara Venuti, Ivette M. Sandoval, Yiyi Yang, Jennifer Stancati, Martina Mazzocchi, Edoardo Brandi, Gerard O’Keeffe, Kathy Steece-Collier, Jia-Yi Li, Tomas Deierborg, Fredric P. Manfredsson, Marcus Davidsson, Andreas Heuer Microglial cells are brain-specific macrophages that swiftly react to disruptive events in the brain. Microglial activation leads to specific modifications, including proliferation, morphological changes, migration to the site of insult, and changes in gene expression profiles. A change in inflammatory status has been linked to many neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease. For this reason, the investigation and quantification of microglial cells is essential for better understanding their role in disease progression as well as for evaluating the cytocompatibility of novel therapeutic approaches for such conditions. In the following study we implemented a machine learning-based approach for the fast and automatized quantification of microglial cells; this tool was compared with manual quantification (ground truth), and with alternative free-ware such as the threshold-based ImageJ and the machine learning-based Ilastik. We first trained the algorithms on brain tissue obtained from rats and non-human primate immunohistochemically labelled for microglia. Subsequently we validated the accuracy of the trained algorithms in a preclinical rodent model of Parkinson’s disease and demonstrated the robustness of the algorithms on tissue obtained from mice, as well as from images provided by three collaborating laboratories. Our results indicate that machine learning algorithms can detect and quantify microglial cells in all the three mammalian species in a precise manner, equipotent to the one observed following manual counting. Using this tool, we were able to detect and quantify small changes between the hemispheres, suggesting the power and reliability of the algorithm. Such a tool will be very useful for investigation of microglial response in disease development, as well as in the investigation of compatible novel therapeutics targeting the brain. As all network weights and labelled training data are made available, together with our step-by-step user guide, we anticipate that many laboratories will implement machine learning-based quantification of microglial cells in their research.
Læs mere Tjek på PubMedInfectious Disease Modelling, 24.04.2023
Tilføjet 24.04.2023
Publication date: June 2023 Source: Infectious Disease Modelling, Volume 8, Issue 2 Author(s): Alexei Alexeevich Romanyukha, Konstantin Alexandrovich Novikov, Konstantin Konstantinovich Avilov, Timofey Alexandrovich Nestik, Tatiana Evgenevna Sannikova
Læs mere Tjek på PubMedInfection, 12.02.2023
Tilføjet 12.02.2023
Abstract Background HPV vaccination has been recommended and reimbursed for girls in Germany since 2007. In June 2018 the German Standing Committee on Vaccination (STIKO) recommended the gender-neutral vaccination of adolescents aged 9 to 14 years with catch-up through age 17. Objectives of this study were to describe the uptake of vaccination in boys before and during the COVID-19 pandemic. Methods The study used data from a proprietary electronic medical record database and a database with information on nationally dispensed vaccine doses. The monthly number of first doses of HPV vaccinations in boys and girls aged 9–17 years in the period from 01/2018 to 12/2021 was determined. In addition, for boys the cumulative vaccination rates were calculated for initiated and completed vaccination series. Results Four months after the introduction of mandatory reimbursement for boys, the monthly numbers of first doses were comparable to that of girls. Compared to the same month in 2019, the number of first doses declined by up to 49% (girls) in 2020 and 71% (boys) in 2021. At the end of 2021, the vaccination rate for 15-year-old boys (2006 birth cohort) reached 44.4% for initiated and 26.4% for completed series. Conclusion After an initial dynamic increase in HPV vaccinations in boys, the impact of COVID-19 was particularly strong in the second year of the pandemic. At the end of 2021 vaccination rates were still low. Efforts are needed to catch-up on adolescents that missed doses during the pandemic and to increase uptake.
Læs mere Tjek på PubMedBMC Infectious Diseases, 28.09.2022
Tilføjet 28.09.2022
Abstract
Background
Despite recommendations from the German Standing Committee on Vaccination (STIKO), pneumococcal vaccination coverage remains low in vulnerable populations. This study estimated the pneumococcal vaccination coverage rate (VCR) and timing among individuals aged 16–59 years in Germany who were recommended to receive pneumococcal vaccination, according to STIKO.
Methods
A retrospective cohort analysis was conducted using the German InGef database. Individuals aged 16 to 59 years diagnosed with at least one “at-risk” (chronic disease) or “high-risk” (e.g., immunocompromising) condition considered to be at-risk of pneumococcal infection were identified at the time of first diagnosis, between January 1, 2016 and December 31, 2018, and followed up until December 31, 2019. The percentage of cumulative pneumococcal VCR with 95% confidence interval (CI) was reported for each calendar year of follow-up.
Results
There were 334,292 individuals followed for a median of 2.38 (interquartile range (IQR) 1.63–3.13) person years. For individuals aged 16–59 years diagnosed with an incident risk condition in 2016, pneumococcal VCR increased from 0.44% (95% CI 0.41–0.48) in 2016 to 1.24% (95% CI 1.18–1.30) in 2019. In 2019, VCRs were higher in individuals with high-risk conditions compared with at-risk conditions (2.24% (95% CI 2.09–2.40) vs. 0.90% (95% CI 0.85–0.96)). In 2019, VCRs were higher in individuals aged 50 to 59 years compared with individuals aged 16 to 49 years (2.25% (95% CI 2.10–2.41) vs. 0.90% (95% CI 0.84–0.96)). Similar trends were observed in individuals with newly diagnosed risk conditions identified in 2017 and in 2018. Older age, influenza vaccination and increasing number of risk conditions increased the likelihood of pneumococcal vaccination. Median time to vaccination from diagnosis of the risk condition was shorter for high-risk conditions (369.5 days (IQR 155.8–702.0)) compared to at-risk conditions (435.5 days (IQR 196.3–758.8)).
Conclusion
Despite recommendations from STIKO, pneumococcal vaccination coverage remains very low and with long delays in vulnerable individuals aged 16–59 in Germany. Further efforts are required to increase immunization levels and shorten time to vaccination among individuals 16–59 years of age developing conditions with higher susceptibility to pneumococcal infection.
Læs mere Tjek på PubMed