Presence Of Viral Infection Research Articles

Efficacy of immune checkpoint inhibitors differs in various status of carcinoma: a study based on 29 cohorts with 3255 participants

BackgroundPre-clinical data have revealed that viral infection, such as Hepatitis B virus (HBV), Hepatitis C virus (HCV), and Human Papilloma virus (HPV), may lead to the development of “hot” or “immune-sensitive” tumors, which may impact the efficacy of immune checkpoint inhibitor (ICIs). Therefore, This study aimed to investigate the impact of viral status on the efficacy of ICIs.MethodsElectronic databases were searched to identify relevant trials. The primary endpoints were overall survival (OS) and progression-free survival (PFS) measured by hazard ratio (HR). Stratified analyses were accomplished based on viral types, treatment regimens, and patient locations.ResultsA total of 3255 participants were recruited, including 252 cases of gastric cancer, 156 cases of nasopharyngeal carcinoma, 1603 cases of hepatocellular carcinoma, and 1244 cases of head and neck squamous cell carcinoma. Pooled results demonstrated a significant association between viral infection and favorable outcomes in patients receiving ICIs, including improved OS [HR = 0.67, 95%CI (0.57–0.79), P < 0.0001], increased ORR [OR = 1.43, 95%CI (1.14–1.80), P = 0.0018], and a trend toward enhanced PFS [HR = 0.75, 95%CI (0.56–1.00), P = 0.05]. In subgroup analyses, patients treated with ICIs who were exposed to HBV/HCV or HPV infection exhibited an evidently superior OS without heterogeneity, compared to those without infection.ConclusionsThis study indicated that the presence of viral infection was evidently associated with improved outcomes in cancer patients undergoing ICIs, particularly in cases of HBV/HCV and HPV infections.

Abstract 3401: Uncovering virus induced dysregulated processes in cancer and their impact on outcomes

Abstract The National Cancer Institute has designated several viruses such as EBV, HBV, HCV, HIV, HPV, and HTLV as agents that either cause cancer or increase the risk of developing cancer. However, extensive analyses of tumor genome and transcriptome datasets have identified numerous additional virus types, the functional implications of which remain largely unknown. Viral infection often dysregulates unique molecular processes within tumor cells and alters the composition of immune cells in the tumor microenvironment. For instance, HPV-positive tumors have been shown to exhibit a significantly elevated expression of the DNA editing enzyme APOBEC3B compared to HPV-negative tumors. Furthermore, HPV positive tumors display and increased number of C-to-T mutations induced by this protein. The genome and transcriptome of tumor tissue biopsies contain a wealth of information about these virus-associated signatures. However, advanced signal processing approaches are needed to extract these viral signatures from complex tumor datasets, and elucidate their specific roles in cancer. Here, we developed a quantitative approach to investigate the link between viral infection and dysregulation of a seven-membered A3 enzyme family (A3A/B/C/D/F/G/H). The primary role of these enzymes is to restrict viral infections by inducing C-to-U mutations in viral genomes. However, at least three members of this enzyme family (A3A/B/H) can also induce mutations in cellular DNA, and drive tumor formation and evolution. We used NMF (Nonnegative Matrix Factorization) to deconvolute the expression profiles of A3 enzymes in &amp;gt;10,000 bulk RNAseq datasets from diverse TCGA tumors. This analysis revealed the expression profiles of A3 enzymes within tumor and tumor microenvironment cells including various immune cells. Next, we conducted an association analysis to identify the link between the presence of viral infection and the proportion of each of these tumor and tumor microenvironment expression profiles. As expected, our analyses revealed strong associations between tumor-specific A3 expression profiles and infections by oncolytic viruses such as HPV. Notably, and somewhat unexpectedly, our analyses also revealed associations with viruses about which little is known in the field of cancer. For example, in certain tumors, we identified a robust association between bacteriophages and a tumor-specific A3 expression profile characterized by A3B upregulation. Taken together, our analyses provide evidence for the link between A3 dysregulation and infection by viruses including bacteriophages. Citation Format: Mohadeseh Soleimanpour moghadam, Azad Khosh, Diako Ebrahimi. Uncovering virus induced dysregulated processes in cancer and their impact on outcomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3401.

First Report of Natural Infection of Watermelon mosaic virus (WMV) Infecting Bottle Gourd and Snake Melon

Cucurbitaceous crops, one of the main crops of agriculture, are sensitive to many plant viruses. In August 2019, virus-like symptoms were observed on some cucurbit plants grown in private home gardens in Antalya and Denizli provinces (Turkey). A total of 53 leaf samples were sampled from plants with the most symptoms (melon (Cucumis melo L.), watermelon (Citrullus lanatus L.), bottle gourd (Lagenaria siceraria (Molina) Standl.), and snake melon (Cucumis melo var. flexuosus) and tested by Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR) against possible watermelon mosaic potyvirus (WMV) infection. The coat protein gene (CP) specific primer sets amplified a gene product of nearly 820 bp fragment from symptomatic plants. WMV infections were detected in 31 individual cucurbit plants, including 11 melons, 8 watermelons, 7 snake melons and 5 bottle gourds. The presence of viral infection was found only in ornamental squash plants in Antalya province and in all cucurbits sampled in Denizli province. To better comprehend the molecular characteristics of virus isolates, the amplified viral DNA fragments were cloned in a proper prokaryotic plasmid, sequenced by Next Generation Sequencing (NGS) and recorded to GenBank. Bioinformatic analyses using the Basic Local Alignment Search Tool (BLAST) showed that the identified CP gene sequences exhibited significant nucleotide homogeneity, supported by a high nucleotide similarity index with that of other isolates around the world. In addition, Turkish isolates isolated from Antalya and Denizli regions showed approximately 94% nucleotide similarity among themselves. For phylogenetic inference, WMV sequences were subjected to multiple alignments with isolates from different geographic origins of the same viruses. Molecular phylogeny showed that all WMV isolates are closely related to other world WMV isolates at variable rates. WMV is wide host range viruses in cucurbit crops, however, this work is the first scientific report of WMV isolates detected in bottle gourd and snake melon from the South and West Regions of Turkey all over the world.WMV are broad spectrum viruses in cucurbit crops. This work is the first scientific report of Watermelon mosaic potyvirus isolates detected in bottle gourd and snake melon from the South-West Region of Turkey in all over the world.

Liquid saliva-based Raman spectroscopy device with on-board machine learning detects COVID-19 infection in real-time.

With greater population density, the likelihood of viral outbreaks achieving pandemic status is increasing. However, current viral screening techniques use specific reagents, and as viruses mutate, test accuracy decreases. Here, we present the first real-time, reagent-free, portable analysis platform for viral detection in liquid saliva, using COVID-19 as a proof-of-concept. We show that vibrational molecular spectroscopy and machine learning (ML) detect biomolecular changes consistent with the presence of viral infection. Saliva samples were collected from 470 individuals, including 65 that were infected with COVID-19 (28 from hospitalized patients and 37 from a walk-in testing clinic) and 251 that had a negative polymerase chain reaction (PCR) test. A further 154 were collected from healthy volunteers. Saliva measurements were achieved in 6 minutes or less and led to machine learning models predicting COVID-19 infection with sensitivity and specificity reaching 90%, depending on volunteer symptoms and disease severity. Machine learning models were based on linear support vector machines (SVM). This platform could be deployed to manage future pandemics using the same hardware but using a tunable machine learning model that could be rapidly updated as new viral strains emerge.

The Streptomyces chromofuscus Strain RFS-23 Induces Systemic Resistance and Activates Plant Defense Responses against Tomato Yellow Leaf Curl Virus Infection

Insect-vectored plant viruses pose a serious threat to sustainable production of economically important crops worldwide. This demands a continuous search for environmentally-friendly, sustainable and efficient approaches based on biological agents to address the mounting challenges of viral disease management. To date, the efficacy of actinomycetes bacteria against DNA plant viruses remains unknown. Here, through comparative analyses, we demonstrate that the RFS-23 strain of Streptomyces cellulase possesses protective activity as it positively regulated the plant growth and development. and diminished the severity, of disease symptoms, together with reduced accumulation of Tomato yellow leaf curl virus (TYLCV) DNA. The RFS-23 strain maintained relative chlorophyll contents by promoting the expression of genes (CLH1, HEMA1 and PORA) associated with chlorophyll biogenesis. As compared to another strain, CTF-20, the RSF-23 induced a significantly higher expression of plant defense-related genes (NbCIS and NbNCED) associated with biogenesis and accumulation of salicylic acid and abscisic acid. Additionally, the activity of antioxidant enzymes (SOD, CAT, POD and MDA) was significantly enhanced by RSF-23 treatment, despite the presence of viral infection. These findings suggest that RSF-23 is a novel biocontrol agent with protective activity, and it could be a potential candidate for the management of plant viral infections.

Impact of e-cigarette aerosol on primary human alveolar epithelial type 2 cells.

Electronic cigarettes (e-cigarettes) are designed to simulate combustible cigarette smoking and to aid in smoking cessation. Although the number of e-cigarette users has been increasing, the potential health impacts and biological effects of e-cigarettes are still not fully understood. Previous research has focused on the biological effects of e-cigarettes on lung cancer cell lines and distal airway epithelial cells; however, there have been few published studies on the effect of e-cigarettes on primary lung alveolar epithelial cells. The primary purpose of this study was to investigate the direct effect of e-cigarette aerosol on primary human lung alveolar epithelial type 2 (AT2) cells, both alone and in the presence of viral infection. The Melo-3 atomizer caused direct AT2 cell toxicity, whereas the more popular Juul pod's aerosol did not have a detectable cytotoxic effect on AT2 cells. Juul nicotine aerosol also did not increase short-term susceptibility to viral infection. However, 3 days of exposure upregulated genes central to the generation of reactive oxygen species, lipid peroxidation, and carcinogen metabolism and downregulated key innate immune system genes related to cytokine and chemokine signaling. These findings have implications for the potentially injurious impact of long-term use of popular low-power e-cigarette pods on the human alveolar epithelium. Gene expression data might be an important endpoint for evaluating the potential harmful effects of vaping devices that do not cause overt toxicity.

SARS-CoV-2 and Prevotella spp.: friend or foe? A systematic literature review.

During this global pandemic of the COVID-19 disease, a lot of information has arisen in the media and online without scientific validation, and among these is the possibility that this disease could be aggravated by a secondary bacterial infection such as Prevotella, as well as the interest or not in using azithromycin, a potentially active antimicrobial agent. The aim of this study was to carry out a systematic literature review, to prove or disprove these allegations by scientific arguments. The search included Medline, PubMed, and Pubtator Central databases for English-language articles published 1999-2021. After removing duplicates, a total of final eligible studies (n=149) were selected. There were more articles showing an increase of Prevotella abundance in the presence of viral infection like that related to Human Immunodeficiency Virus (HIV), Papillomavirus (HPV), Herpesviridae and respiratory virus, highlighting differences according to methodologies and patient groups. The arguments for or against the use of azithromycin are stated in light of the results of the literature, showing the role of intercurrent factors, such as age, drug consumption, the presence of cancer or periodontal diseases. However, clinical trials are lacking to prove the direct link between the presence of Prevotella spp. and a worsening of COVID-19, mainly those using azithromycin alone in this indication.

Bovine Coronavirus Infects the Respiratory Tract of Cattle Challenged Intranasally.

Bovine Coronavirus (BCoV) is a member of a family of viruses associated with both enteric and respiratory diseases in a wide range of hosts. BCoV has been well-established as a causative agent of diarrhea in cattle, however, its role as a respiratory pathogen is controversial. In this study, fifteen calves were challenged intranasally with virulent BCoV in order to observe the clinical manifestation of the BCoV infection for up to 8 days after initial challenge, looking specifically for indication of symptoms, pathology, and presence of viral infection in the respiratory tract, as compared to six unchallenged control calves. Throughout the study, clinical signs of disease were recorded and nasal swabs were collected daily. Additionally, bronchoalveolar lavage (BAL) was performed at 4 days Post-challenge, and blood and tissue samples were collected from calves at 4, 6, or 8 days Post-challenge to be tested for the presence of BCoV and disease pathology. The data collected support that this BCoV challenge resulted in respiratory infections as evidenced by the isolation of BCoV in BAL fluids and positive qPCR, immunohistochemistry (IHC), and histopathologic lesions in the upper and lower respiratory tissues. This study can thus be added to a growing body of data supporting that BCoV is a respiratory pathogen and contributor to respiratory disease in cattle.

Expression of Podoplanin in Hepatocellular Carcinoma in a Sample of Egyptian Population – Immunohistopathological Study

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly incident malignancy with a dreadful prognosis. It evolves through a multistep process, with a contribution from different stromal cells like cancer associated fibroblasts. Podoplanin is a glycoprotein that influences epithelial mesenchymal interplay facilitating the tumor invasion. AIM: The aim of the study was to evaluate the immunohistochemical expression of Podoplanin in HCC in cancer associated fibroblasts (CAFs) and malignant hepatocytes as well as assessing the lymphovascular density, and correlating them with the clinicopathological parameters. METHODS: Sixty formalin-fixed paraffin-embedded HCC tissue blocks were retrieved from the pathology Department of the National Hepatology and Tropical Medicine Research Institute and Kasr Al-aini Hospital during the period of January 2012 till December 2019. The specimens were obtained through partial or total hepatectomy inclusion criteria included HCC cases obtained through resection type biopsy and those having no history of pre-operative cancer therapy, while cases with insufficient data, core biopsy, and marked necrosis were excluded from the study. Tumor tissue blocks were immunostained for Podoplanin and its expression was interpreted in lymphatic vessels, CAFs, and malignant hepatocytes. RESULTS: Podoplanin expression in CAFs and malignant hepatocytes was detected in the majority of HCC cases (81.7%) and (88.3%), respectively. The malignant hepatocytes showed increased expression of Grade 1 immunostaining (36.7%). High lymphovascular density was detected over the majority of the cases (73.3%). Podoplanin expression was significantly correlated with higher mean age, male gender, presence of viral infection, cirrhosis, and higher tumor grade. Unifocal tumor mass, tumor size &lt;5 cm, and presence of invasion showed a significant correlation with Podoplanin in malignant hepatocytes and CAFs for the formers and the later, respectively. CONCLUSION: Podoplanin is highly expressed in HCC, which could be used as a prognostic marker for lymphangiogenesis. Furthermore, within the malignant hepatocytes and CAFs suggesting a role in hepatocellular tumorigenesis. Podoplanin targeted therapy can be investigated to slow down the tumor progression and metastasis.

Response of Cucumber (Cucumis sativus L.) Varieties Against TMV (Tobacco mosaic virus) Infection

The tobacco mosaic virus (TMV) is a Tobamovirus that can infect cucumber plants. There is limited information about the response of cucumber varieties against TMV infection. The research was conducted to evaluate the response of cucumber varieties to TMV infection using TMV isolates from Bogor. The evaluation of resistance to TMV isolates was conducted by sap transmission method using TMV isolates from Bogor that propagated on tobacco as the source of inoculum. Variable observations covered the period of incubation (the day after inoculation/DAI), the symptoms of the disease, disease incidence, and disease severity. The presence of viral infection was observed through the accumulation of starch and inclusions bodies. Based on the results of the research, the TMV isolate was able to infect systematically all tested plants with symptoms of which appear in the form of mosaic light to heavy with the incidence of the disease reaching 100%. Response of cucumbers varieties to TMV isolate can be categorized into resistant (Bandana F1, Neptun, and Pandu), tolerant (Ethan F1), and susceptible (Vario F1).

Age-related Differences in the Nasal Mucosal Immune Response to SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 180 million people since the onset of the pandemic. Despite similar viral load and infectivity rates between children and adults, children rarely develop severe illness. Differences in the host response to the virus at the primary infection site are among the mechanisms proposed to account for this disparity. Our objective was to investigate the host response to SARS-CoV-2 in the nasal mucosa in children and adults and compare it with the host response to respiratory syncytial virus (RSV) and influenza virus. We analyzed clinical outcomes and gene expression in the nasal mucosa of 36 children with SARS-CoV-2, 24 children with RSV, 9 children with influenza virus, 16 adults with SARS-CoV-2, and 7 healthy pediatric and 13 healthy adult controls. In both children and adults, infection with SARS-CoV-2 led to an IFN response in the nasal mucosa. The magnitude of the IFN response correlated with the abundance of viral reads, not the severity of illness, and was comparable between children and adults infected with SARS-CoV-2 and children with severe RSV infection. Expression of ACE2 and TMPRSS2 did not correlate with age or presence of viral infection. SARS-CoV-2–infected adults had increased expression of genes involved in neutrophil activation and T-cell receptor signaling pathways compared with SARS-CoV-2–infected children, despite similar severity of illness and viral reads. Age-related differences in the immune response to SARS-CoV-2 may place adults at increased risk of developing severe illness.

Use of heart rate variability to predict hospital length of stay for COVID-19 patients: A prospective observational study.

Background:As the COVID-19 pandemic continues, determining hospital demands has become a vital priority. Heart rate variability (HRV) has been linked to both the presence of viral infection and its severity. We investigate the possibility of using HRV parameters in comparison to other clinical parameters for predicting the hospital length of stay (LOS) for COVID-19 patients.Methods:This was a population-based cohort study. Measurements were performed in a specialized hospital for respiratory disease, dedicated to COVID-19. Patients were polymerase chain reaction positive for COVID-19 and on their 1st day of admission. Heart period, respiratory sinus arrhythmia (RSA), low frequency (LF) HRV, and vagal efficiency were calculated from electrocardiogram signals. This study investigated the correlation of HRV, demographic, and laboratory parameters with hospital LOS.Results:Forty-one participants were recruited, with a significant relationship, observed between hospital LOS and some demographic and clinical parameters such as lymphocyte count, age, and oxygen saturation of arterial blood. There was a negative relationship between LF and hospital LOS (r = −0.53, 95% confidence interval: −0.73, −0.24). Higher vagal efficiency predicted shorter hospital LOS in patients younger than 40 years of age (19.27% shorter hospital LOS was associated with a one SD higher value of VE, P = 0.007).Conclusion:HRV measurement is a non-invasive, inexpensive, and scalable procedure that produces several metrics, some of which are useful for predicting hospital LOS and managing treatment resources during COVID-19 pandemic.

MO1015EARLY URINARY SYSTEM COMPLICATIONS IN CHILDREN WITH HEMATOPOETIC STEM CELL TRANSPLANTATION

Abstract Background and Aims Urinary system complications after hematopoietic stem cell transplantation (HSCT) cause severe morbidity and mortality. The aim of the study is to investigate the incidence and risk factors of urinary system complications in patients who had HSCT during their childhood. Method Patients who had HSCT between January 2010-2019 with a minimum follow-up period of 6 months were included in the study. Data regarding urinary system complications were collected from the medical records of the patients. pRIFLE and KDIGO classification systems were used for the definition of acute kidney injury (AKI). Results 167 patients (108 males and 59 females) with allogeneic (n=165) and autologous (n=2) HSCT were investigated for renal complications. In cohort, HSCT was performed in 41 patients (%24.6) secondary to malignant diseases and in 126 patients secondary to non-malignant diseases. Hemorrhagic cystitis (HC) developed in 28 patients (16.8%) after HSCT. The mean age of the patients with and without HC was 14.6±5.6 years and 10.5±6 years, respectively (p=0.044). Among patients with HC, 17 had concomitant viral infection. Presence of viral infection, gender, disease group, history conditioning regime, total body irradiation, acute graft-versus-host disease and veno-occlusive disease (VOD) did not have any effect on the development of HC in logistic regression analysis. In cohort, 126 patients (75.4%) developed AKI according to KDIGO classification (stage 1; 55 patients, stage 2; 36 patients, stage 3; 35 patients). The mean period of development of AKI after HSCT was 34±22 days. The risk of AKI (according to KDIGO) was higher in patients who had HSCT secondary to malignant diseases and/or who developed viral infections after HSCT (p=0.034 and p=0.013, respectively). Among patients, 71 patients (%42.5) developed AKI according to pRIFLE classification. The risk of AKI (according to pRIFLE) was higher in patients who had HSCT secondary to malignant diseases, who developed viral infections and/or who developed VOD during follow-up (p=0.043, p=0.001 and p=0.006, respectively). One patient developed thrombotic microangiopathy after HSCT. None of the patients had nephrotic syndrome during follow-up period. Conclusion Patients who had HSCT secondary to malignant disease, viral infections and/or VOD had higher risk of AKI and should be closely monitored.

A molecular survey of canine respiratory viruses in New Zealand

ABSTRACT Aims The aim of this study was to identify viruses associated with canine infectious respiratory disease syndrome (CIRDS) among a population of New Zealand dogs. Methods Convenience samples of oropharyngeal swabs were collected from 116 dogs, including 56 CIRDS-affected and 60 healthy dogs from various locations in New Zealand between March 2014 and February 2016. Pooled samples from CIRDS-affected (n = 50) and from healthy (n = 50) dogs were tested for the presence of canine respiratory viruses using next generation sequencing (NGS). Individual samples (n = 116) were then tested by quantitative PCR (qPCR) and reverse transcriptase qPCR (RT-qPCR) for specific viruses. Groups were compared using Fisher’s exact or χ2 tests. The effect of explanatory variables (age, sex, type of household, presence of viral infection) on the response variable (CIRDS-affected or not) was tested using RR. Results Canine pneumovirus (CnPnV), canine respiratory coronavirus (CRCoV), canine herpesvirus-1 (CHV-1), canine picornavirus and influenza C virus sequences were identified by NGS in the pooled sample from CIRDS-affected but not healthy dogs. At least one virus was detected by qPCR/RT-qPCR in 20/56 (36%) samples from CIRDS dogs and in 23/60 (38%) samples from healthy dogs (p = 0.84). CIRDS-affected dogs were most commonly positive for CnPnV (14/56, 25%) followed by canine adenovirus-2 (CAdV-2, 5/56, 9%), canine parainfluenza virus (CpiV) and CHV-1 (2/56, 4% each), and CRCoV (1/56, 2%). Only CnPnV (17/60, 28%) and CAdV-2 (14/60, 23%) were identified in samples from healthy dogs, and CAdV-2 was more likely to be detected healthy than diseased dogs (RR 0.38; 95% CI = 0.15–0.99; p = 0.045) Conclusions The frequency of detection of viruses traditionally linked to CIRDS (CAdV-2 and CPiV) among diseased dogs was low. This suggests that other pathogens are likely to have contributed to development of CIRDS among sampled dogs. Our data represent the first detection of CnPnV in New Zealand, but the role of this virus in CIRDS remains unclear. On-going monitoring of canine respiratory pathogens by NGS would be beneficial, as it allows rapid detection of novel viruses that may be introduced to the New Zealand canine population in the future. Such monitoring could be done using pooled samples to minimise costs. Clinical relevance Testing for novel respiratory viruses such as CnPnV and CRCoV should be considered in all routine laboratory investigations of CIRDS cases, particularly in dogs vaccinated with currently available kennel cough vaccines.

Pan-cancer analysis of genomic properties and clinical outcome associated with tumor tertiary lymphoid structure

How the genomic landscape of a tumor shapes the formation of tertiary lymphoid structure (TLS) and how might TLS alter the clinical outcome or response to immunotherapy had not been systematically explored. Utilizing the genomic and transcriptome data of solid tumors on TCGA, we quantified TLS based on a previous identified 12-chemokine signature and evaluated its correlation with mutation/neoantigen burden, functional mutation of oncogenes and the presence of viral infection. Clinical data was integrated to decide the prognostic significance of TLS for different cancers after surgical treatment. Publicly available data (clinical and transcriptome data) of immunotherapy clinical trials involving melanoma and lung cancer were also collected to evaluate TLS’s association with therapeutic outcome. Mutation burden and predicted neoantigen counts were positively correlated with TLS scoring in multiple cancer types. Mutation in tumor suppressor genes (KEAP1, PBRM1) and genes involved in extrinsic apoptosis (CASP8), antigen-presentation (HLA-A, HLA-B), immune regulation (SMAD4) or DNA repair (BRCA1, BRCA2, TP53BP1) correlated with TLS alteration in multiple tumor types, indicating the interaction between mutation landscape and TLS formation. Epstein-Barr virus (EBV) infection in gastric cancer and human papillomavirus (HPV) infection in Head and Neck squamous cell carcinoma were associated with increased TLS scoring. High TLS scoring predicted favorable prognosis in certain cancer after surgical treatment and improved response to immunotherapy in lung cancer and melanoma. Our findings unraveled the genomic properties associated with TLS formation in different solid tumors and highlighted the prognostic and predictive significance of TLS in surgical treatment and immunotherapy.

Risk of Unsatisfactory Functional Outcome of Stroke in Patients with Clinical Manifestation of Persistent Viral Infection

Acute cerebrovascular disorders represent up to 75–85 % of strokes inUkraine. The wide spread of herpesvirus infection in developing countries (with a prevalence of 35–40 %), as well as influenza virus, requires consideration of the viral risk factor of stroke for prognostic purposes.The objective: to study the influence of the most common types of viral infection: the family of herpesviruses and influenza virus on the neurological and one-year functional outcome of stroke and to determine the predictors of unsatisfactory recovery of patients.Materials and methods. In the period from 2016–2020, on the basis of the neurological departments ofAlexanderHospital andClinicalHospital № 4 we performed research on the presence of herpes viruses. 70 patients with ischemic stroke with moderate and severe neurological disorders were examined, in whom herpes and influenza viruses were detected in the blood (the main group) within 2 weeks before hospitalization against the background of viral manifestation. The comparison group consisted of 220 patients without clinical signs of viral manifestations were compared with the main group by stroke severity, average age and gender. The severity of neurological disorders was assessed by the NIHSS scale. Functional recovery was assessed by the Barthel index. The presence of viral infection (family of herpesviruses and influenza virus) was studied using polymerase chain reaction.Results. HSV1 DNA was detected in 43 (61.4 %) cases, HSV2 – in 30 (42.9 %), EBV4 – in 19 (27.1 %), CMV5 – in 18 (25.7 %), HNV6 – in 27 (38.6 %), Influenza RNA – in 16 (22.9 %). Only one type of virus was present in 21 (30.0 %) patients, two types of viruses were identified in 31 (44.3 %), three or more types of viruses – in 18 (25.7 %). In the presence of viral infection, the relative risk of unsatisfactory recovery of neurological functions in the main group increases 1.99 times relative to the comparison group: RR=1.99 (95 % CI: 1.60–2.48). The presence of viral infection predicted unsatisfactory recovery with a sensitivity of 74.3 %, a specificity of 62.7 % and an area under the curve ROC=0.69. There was a negative correlation between increasing the number of virus types in patients and the lack of neurological improvement: r=0.370 (p=0.002). The presence of viral infection significantly increased the risk of moderate and severe disability one year after stroke, the relative risk of disability in patients of the main group relative to patients of comparison group was: RR=1,668 (95 % CI: 1,256–2,214), and IB score according to the linear regression analysis inversely depended on the number of viruses in patients, linear R2=0.423 (correlation coefficient r=–0.660). In the presence of two types of viruses in the blood, the probability of unsatisfactory recovery increased – 1.5 times (RR=1,562; 95 % CI: 1,064–2,265), three or more viruses 2.5 times (RR=2,511; 95 % CI: 1,888–3,340). One year after stroke, there was a significant correlation between lower IB score and the presence of HSV1 in associations: r=0.323; CMV: r=0.351; EBV: r=0.430. If there are at least 2 types of viruses in the blood, in particular HSV1+CMV and HHV6+CMV, the relative risk of PI and TI increases 2.9 times.Conclusions. The presence of a viral infection significantly increases the risk of unsatisfactory regression of neurological disorders, allows to predict poor neurological recovery with a sufficiently high sensitivity and specificity. In patients with viral manifestations and detection of the virus in the blood, functional recovery one year after stroke is significantly worse than in patients without it; this applies to a lower mean score of IB and the percentage of patients with minimal limitation of function. When the number of persistent viruses increases to two or more, the relative risk of PI and TI increases one year after stroke, with the highest rate in the presence of EBV and CMV associations. If there are at least 2 types of viruses in the blood, in particular HSV1+CMV, HHV6+CMV, HSV1+EBV the relative risk of PI and TI increases 2.9 times.

Вірусінфікований калюс квасолі та його оздоровлення in vitro за дії ліпосомальних препаратів

The aim of the study was to develop a recovery means for beans infected by Bean yellow mosaic virus (BYMV) as well as Bean common mosaic virus (BCMV) using callus culture and liposomal glycan preparations. Methods. Cultivation of explants and callus cultures was carried out in vitro using conventional methods of plant biotechnology. The tissue culture propagation was performed during the spring or summer seasons. The presence of viral infection was tested by reverse transcription polymerase chain reaction. The virus-specific primers that allowed amplifying the conserved regions of the capsid protein gene of BCMV or BYMV were used for virus identification. Results. The culture of bean callus infected with BCMV was obtained and adapted for antiviral agents testing. It has been shown that during long-term cultivation (10–12 weeks) in the presence of liposomal preparation containing Ganoderma adspersum glucan (10–100 mg/l), plant tissue culture become free from viruses following virus eradication. This is evidenced by the absence in the callus tissue of 391 bp sequences typical for the virus coat protein gene. Conclusions. The full suppression of virus reproduction and gradual elimination of virus occurred in callus tissue obtained from BCMV-infected beans and cultured on B-5 medium supplemented with liposomal glycanglycolipid complex (10–100 mg/l). The data obtained can be useful for the development of practical control method to cure plant virus diseases using callus culture and antiviral-active glycan-glycolipid complexes.

Risk of a three-year ischemic stroke recurrence and its independent predictors in patients with a confirmed manifestationof viral infection

Objective — to assess the risk of the manifest viral infection impact on the three‑year frequency of the recurrent stroke and to determine its independent predictors.Methods and subjects. From 2014 to 2019 70 patients with ischemic stroke with viral infection manifestation during 2 weeks before hospitalization were examined. The presence of viral infection was confirmed by a polymerase chain reaction (main group). A total of 220 patients without viral manifestation were included in the comparison group, who were compared with the main group by stroke severity, average age and gender. The severity of neurological deficiency was assessed by the NIHSS scale. The pathogenetic subtype of stroke was determined according to TOAST criteria.Results. Over the three‑year period, the three‑year cumulative rate of stroke recurrence was higher in main group patients — 17.4 % (non‑recurring survival 82.6 ± 4.58 %) than in comparison group — 12.1 % (non‑recurring survival 87.9 ± 2.2 %), p = 0.240. In the case of at least 2 types of viruses genomes presence in the blood, the frequency of recurrence has increased to 22.8 % (probability of non‑recurring survival 77.2 6.05 %), in comparison group — 12.1 % (probabilityofnon‑recurringsurvival 87.9 2 %), p = 0.0470. In the case of HSV1 determination, the risk of a stroke reccurence in the main group comparing to comparison group patients increased by 2.16 times: BP = 2.16; 95 % CI: 1.15 — 4.04 (p = 0.0154); HSV2 : 1.69: BP = 1.69; 95 % CI: 0.76 — 3.77 (p = 0.1983); HNV6 : 2.49: BP = 2.49; 95 % CI: 1.05 — 4.56 (p = 0.0356); CMV: 2.82: BP = 2.82; 95 % CI: 1.34 — 5.95 (p = 0.0065); EBV: 2.67 times: BP = 2.67; 95 % CI: 1.26 — 5.68 (p = 0.0106); Influenza virus: 2.64 times: BP = 2.64; 95 % CI: 1.17 — 5.95 (p = 0.0188). HSV1 (B coefficient = 4.52), CMV (B coefficient = 3.63), Influenza virus (B coefficient = 4.11), and Intima‑media thickness (B coefficient = 10.77), constant — 20.57 were determined as independent prognostic factors of a three‑year stroke recurrence in patients with viral manifestation. The predictive value of the model is high with an area of the figure under the ROC curve = 0.971, 95 % CI: 0.900 — 0.966 and model sensitivity — 100.0 %, 95 % CI: 71.5 — 100.0 % and specificity — 83.1 % (95 % CI: 71.0 — 91.6 %).Conclusions. The risk of a stroke recurrence with viral manifestation and the presence of herpes virus and influenza virus genome significantly increases in 1.89 times when two or more types of viruses are present and is 22.8 % to GP (12.1 %). The presence of HSV1, CMV DNA, influenza RNA, and Intima‑media thickness in the patient are the independent prognostic factors of a three‑year stroke recurrance in patients with viral manifestation according to the developed mathematical model using the step‑by‑step multivariant binary logistic regression.

P1809EARLY URINARY SYSTEM COMPLICATIONS IN CHILDREN WITH HEMATOPOIETIC STEM CELL TRANSPLANTATION

Abstract Background and Aims Urinary system complications after hematopoietic stem cell transplantation (HSCT) cause severe morbidity and mortality. The aim of the study is to investigate the incidence and risk factors of urinary system complications in patients who had HSCT during their childhood. Method Patients who had HSCT between January 2010-2019 with a minimum follow-up period of 6 months were included in the study. Data regarding urinary system complications were collected from the medical records of the patients. pRIFLE and KDIGO classification systems were used for the definition of acute kidney injury (AKI). Results 167 patients (108 males and 59 females) with allogeneic (n=165) and autologous (n=2) HSCT were investigated for renal complications. In cohort, HSCT was performed in 41 patients (%24.6) secondary to malignant diseases and in 126 patients secondary to non-malignant diseases. Hemorrhagic cystitis (HC) developed in 28 patients (16.8%) after HSCT. The mean age of the patients with and without HC was 14.6±5.6 years and 10.5±6 years, respectively (p=0.044). Among patients with HC, 17 had concomitant viral infection. Presence of viral infection, gender, disease group, history conditioning regime, total body irradiation, acute graft-versus-host disease and veno-occlusive disease (VOD) did not have any effect on the development of HC in logistic regression analysis. In cohort, 126 patients (75.4%) developed AKI according to KDIGO classification (stage 1; 55 patients, stage 2; 36 patients, stage 3; 35 patients). The mean period of development of AKI after HSCT was 34±22 days. The risk of AKI (according to KDIGO) was higher in patients who had HSCT secondary to malignant diseases and/or who developed viral infections after HSCT (p=0.034 and p=0.013, respectively). Among patients, 71 patients (%42.5) developed AKI according to pRIFLE classification. The risk of AKI (according to pRIFLE) was higher in patients who had HSCT secondary to malignant diseases, who developed viral infections and/or who developed VOD during follow-up (p=0.043, p=0.001 and p=0.006, respectively). One patient developed thrombotic microangiopathy after HSCT. None of the patients had nephrotic syndrome during follow-up period. Conclusion Patients who had HSCT secondary to malignant disease, history of viral infections and/or VOD had higher risk of AKI and should be closely monitored.

Сytokine markers for different variants of sclerotic lichen in women

Our work was aimed for studying the role of systemic of IL-23 and IL-20 levels in different clinical variants of sclerotic lichen in women. The study was based on results of clinical data (anamnesis, examination, palpation, vulvoscopy) and immunological studies (determination of IL-20 and IL-23 cytokines in peripheral blood) in the patients with sclerotic lichen (114 patients aged 42.5±15.1 years). Group I included patients with atrophic variant of sclerotic lichen (n = 58); group II, with sclerotic variant of sclerotic lichen (n = 34). Group III included women with a sclero-atrophic variant of this disorder (n = 22). The control group consisted of conditionally healthy women without present, or previously documented vulvar pathology (30 persons). Criteria for inclusion were as follows: women 20 to 60 years old, the presence of a benign vulvar disease, absence of treatment with immunotropic drugs over past year. Exclusion criteria: presence of viral infection (HPV, HSV), detection of STI, presence of acute inflammatory process (including vulvitis and vaginitis), cancer diagnosis, symptoms of autoimmune disorders, pregnancy, and the patient’s reluctance to participate in the study.Predominant increase of IL-23 was revealed in all clinical groups of the examined patients, the most pronounced increase (2.7 times) was in severe sclerotic lichen (p &lt; 0.0001). IL-23 concentration in the 2nd clinical group corresponded to the reference age-matched values. There was a significant increase in the blood content of IL-20 in subgroup 2.2 of the patients with sclerotic lichen (p &lt; 0.0001), as well as in patients from group 3 with a mixed clinical course of its disorder (p &lt; 0.0001). Meanwhile, the absence of pronounced vulvar tissue sclerosis in sclerotic variant of sclerotic lichen (subgroup 2.1) was accompanied only by a tendency for increased IL-20 concentration (p = 0.502), and only a trend for decrease in atrophic variant of sclerotic lichen (p = 0.288). In general, analysis of these data presumes a significant role of IL-20 and IL-23 in pathogenesis of sclerotic lichen in women. The cytokine assays in various clinical variants of this vulvar disorder may provide additional differential diagnostics (IL-20), and to assess severity of atrophic and sclerotic changes in vulvar tissues (IL-23) in women with sclerotic lichen.