Level Of Immunity Research Articles

Forecasting SARS-CoV-2 epidemic dynamic in Poland with the pDyn agent-based model

We employ pDyn (derived from “pandemics dynamics”), an agent-based epidemiological model, to forecast the fourth wave of the SARS-CoV-2 epidemic, primarily driven by the Delta variant, in Polish society. The model captures spatiotemporal dynamics of the epidemic spread, predicting disease-related states based on pathogen properties and behavioral factors. We assess pDyn’s validity, encompassing pathogen variant succession, immunization level, and the proportion of vaccinated among confirmed cases. We evaluate its predictive capacity for pandemic dynamics, including wave peak timing, magnitude, and duration for confirmed cases, hospitalizations, ICU admissions, and deaths, nationally and regionally in Poland. Validation involves comparing pDyn’s estimates with real-world data (excluding data used for calibration) to evaluate whether pDyn accurately reproduced the epidemic dynamics up to the simulation time. To assess the accuracy of pDyn’s predictions, we compared simulation results with real-world data acquired after the simulation date. The findings affirm pDyn’s accuracy in forecasting and enhancing our understanding of epidemic mechanisms.

Integrating Single-cell and Bulk RNA-seq to Construct a Metastasis-related Model for Evaluating Immunotherapy and Chemotherapy in Uveal Melanoma.

Metastasis is a major cause of death in UM, highlighting the need to use highly specific and sensitive prognostic markers to identify patients with a risk of developing metastasis. The aim of this study was to improve the current precision treatment for patients with metastatic uveal melanoma (UM). The objective of this work was to investigate the heterogeneity between primary human UM and metastatic UM at the single-cell level and to discover potential molecules regulating UM metastasis. Seurat R toolkit was employed to analyze single-cell sequencing data of UM and to identify differentially expressed genes (DEGs) between primary and metastatic UM. Least absolute shrinkage and selection operator (LASSO) and Cox regression analyses were performed on the DEGs from the bulk RNA-seq cohort to develop a prognostic model. Based on the model, patients were divided into high and low groups. The correlations among the risk score, immune indicators, immune checkpoint blockade (ICB) therapy, and anti-tumor drug therapy were analyzed. Cell types in primary UM and metastatic UM tumors include B/plasma cells, endothelial cells, melanocytes, monocytes/macrophages, photoreceptor cells, and T cells. Among 157 DEGs between the two tumor types, S100A4, PDE4B, CHCHD10, NSG1, and C4orf48 were selected to construct a prognostic model. The model could accurately and independently predict response to ICB treatment and sensitivity to antineoplastic drugs for UM patients as well as their immune infiltration levels, risk of death, and metastasis possibility. This study analyzed the tumor ecosystem of primary and metastatic UM, providing a metastasis-related model that could be used to evaluate the prognosis, risk of metastasis, immunotherapy, and efficacy of antineoplastic drug treatment of UM.

ITGB4 is a prognostic biomarker and correlated with lung adenocarcinoma brain metastasis.

The aim of this study is to explore the prognostic value and immune signature of ITGB4 expression in lung adenocarcinoma (LUAD) brain metastasis. We comprehensively screened genes associated with LUAD brain metastasis by integrating datasets from the GEO database and TMT-based quantitative proteomics profiles. Univariable survival and Multivariate Cox analysis was used to compare several clinical characteristics with survival, and a risk model was constructed. The biological functions were explored via GO and KEGG analysis. Gene set enrichment analysis (GSEA) was performed using the TCGA dataset. In addition, we use TIMER to explore the collection of ITGB4 Expression and Immune Infiltration Level in LUAD. The ability of ITGB4 to regulate tumor metastasis was further assessed by migration, invasion assay and Western-blot in H1975-BrM4 cells. We found that ITGB4 was the only gene with high clinical diagnostic and prognostic value in LUAD. Enrichment analysis indicated that ITGB4 is associated with brain metastasis, infiltration of immune cells, and the response to immunotherapy. ITGB4 expression can effectively predict the outcomes of patients with LUAD who are receiving anti-PD-1 therapy. ITGB4 knockdown inhibited the invasion, migration of H1975-BrM4 brain metastasis cells, as well as epithelial-mesenchymal transition (EMT) abilities. The heightened expression of ITGB4 protein was shown to promote EMT and enhance the metastatic potential. ITGB4 promotes the progression in H1975-BrM4 cells via MEK/ERK signaling pathway. Our findings indicate that the expression of ITGB4 is linked to the occurrence of brain metastasis and infiltration of immune cells, suggesting that ITGB4 might be a clinical treatment target for LUAD.

Lot quality assurance sampling for coverage evaluation of a new vaccine: A pilot study

BackgroundWorldwide, vaccine-preventable diseases have been a significant cause of mortality in the under-5 age group. To pre-empt the disease burden, new vaccines are being introduced in every country’s immunization programmes. For this to happen, high vaccination coverage is necessary. However, rapidly identifying the areas that fail to reach the expected coverage becomes cumbersome. During recent years, lot quality assurance sampling (LQAS) has been widely used in evaluating immunization coverage across the globe. The present study aims to pilot this approach for field monitoring of a new vaccine against routine concurrent field monitoring in one of the North-Eastern states of India. MethodologyFor LQAS, a community-based cross-sectional study was undertaken among 55 children aged 0–23 months in all 5 Primary health centres (lots) in Medziphema block, Dimapur, Nagaland. The total sample size for LQAS was made based on α = 5, β = 90 using Lemeshow and Taber-LQAS table with a target level of immunization defined as 90 % and the lower limit set to 55 %. For the concurrent field monitoring, a sample of 30 children in the same age group was selected through random sampling. Pre-designed, pre-tested questionnaire for the caregivers, scripted on a digital tool was employed with verification of immunization card and caregiver’s recall. Data was analyzed using SPSS software version 25.0. ResultsThe study found a slight difference in the percentage of children age-appropriately vaccinated for PCV (as per the schedule) in concurrent field monitoring (93.3 %) and LQAS (90.9 %). However, no significant difference was found in statistically comparing the immunization coverage using both methodologies (p > 0.05). ConclusionThe study findings encourage that LQAS can be considered for monitoring the immunization coverage of a newly introduced vaccine. It offers the added advantage of identifying poor/low-performing pockets that require focused attention.

Abstract PR014: DNA associated with EVs is uniquely chromatinized and prevents metastasis by enhancing anti-tumor immunity

Abstract Cells release extracellular vesicles (EVs) loaded with functional biomolecules that facilitate intercellular communication in health and disease. These EVs contain DNA (EV-DNA), mirroring the mutational profile of parental cells, yet the mechanism of DNA packaging onto EVs and its role in diseases like cancer remain unclear. Using advanced imaging and biochemical techniques, we discovered that EV-DNA predominantly resides on the vesicle surface, bound to modified histones. Through genome-wide CRISPR knockout screens in cancer cell lines, we identified immune-related pathways and genes crucial for EV-DNA loading, such as APAF1 and NCF1. In several cancer models, loss of APAF1 reduced EV-DNA packaging, and enhancing metastasis, thus implicating EV-DNA in immune surveillance against cancer spread. We demonstrated that EV-DNA uptake by liver macrophages triggers DNA damage response, altering cytokine production and promoting immune activation in pre-metastatic sites. Moreover, quantifying EV-DNA in colorectal cancer biopsies revealed its potential as a predictive metastatic risk biomarker. Our findings shed light on EV-DNA packaging mechanisms and its significance, suggesting that elevated levels of tumor-derived EV-DNA bolster anti-tumor immunity and inhibit metastasis. Citation Format: Inbal Wortzel, Han-Sang Kim, David C. Lyden. DNA associated with EVs is uniquely chromatinized and prevents metastasis by enhancing anti-tumor immunity [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr PR014.

Single-cell expression and immune infiltration analysis of polyamine metabolism in breast cancer.

Breast cancer is one of the most threatening women health diseases worldwide and its molecular heterogeneity offers a range of response to therapy. The role of polyamine metabolism is receiving increasing attention. Polyamine metabolism not only plays an important role in the occurrence and development of breast cancer, but also interacts with tumor immune microenvironment. In this work, we applied single-cell RNA-sequencing (scRNA-seq) and systems immunological approaches to interrogate immune cell infiltration gene-to-gene co-expressions in the bulk tumor transcriptomes of breast cancer. We acquired breast cancer sample data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), evaluated the infiltration status of 22 immune cell types using CIBERSORTx tool, respectively. By leveraging the Retrospective Breast sample of various technologies including gene expression and methylation, we identified 46 breast cancer proliferation-associated co-expression modules using weighted gene coexpression network analysis (WGCNA) approach along with machine learning models which in turn delineated single cell level expressions features that these selected module possessed. We observed substantial cellular heterogeneity in the breast cancer microenvironment, where lineage-specific gene expression patterns were highly associated with tumor progression. Moreover, we also identified the gene modules correlated with immune cell infiltration level that could function as regulators in response to tumors for immune therapy. Moreover, risk scores were correlated with immune cell function in different patient groups defined by high- and low-risk. The findings of this study shed a new light upon molecular classification prognostic assessment and personalized treatment in breast cancer.

The Relationship Between Systemic Immune Inflammatory Level and Dry Eye in Patients with Sjögren’s Syndrome

Background and objectives: Sjögren Syndrome (SS) is a chronic, systemic, and progressive autoimmune disease in which inflammatory processes play a role. Dry eyes or mouth are present in approximately 95–98% of patients with pSS. This study aimed to evaluate the relationship between SII level and disease activity as well as dry eye involvement in patients with pSS. Materials and methods: A cross-sectional design was employed, and a total of 28 female patients who were aged 18–65 years and were diagnosed with pSS were involved. The Sjögren Syndrome Disease Activity Index (ESSDAI) was calculated in patients. The Schirmer test was applied to all patients. The relationship between SII level and disease activity as well as dry eye involvement in pSS patients was evaluated. Results: In our study, a strong positive correlation was found between the SII value and pSS disease activity, while a negative correlation was found between the Schirmer test, which shows dry eye findings, and eye drying time, and a positive correlation was found with the OSDI. Conclusions: this study reported a correlation between hematological parameters and the development of dry eye in pSS. NLR, PLR, and SII showed statistically significant changes in pSS patients.

A subunit vaccine based on P97R1, P46, P42, and P65 from Mycoplasma hyopneumoniae can induce significant immune response in piglets

Mycoplasma pneumonia (MPS), caused by Mycoplasma hyopneumoniae (Mhp), is a chronic, airborne respiratory disease that poses a significant threat to the global swine industry. The P97 and P46 proteins are major antigens of Mhp, with the R1 region of P97 possessing full adhesive capability. Studies have shown that the main antigenic regions of Mhp P42 and P65 proteins exhibit strong immunogenicity. In this study, we first linked the genes encoding P97R1 and P46 proteins to form the P97R1P65 gene and subsequently constructed three shuttle plasmids: pFBD-P97R1P46, pFBD-P97R1P46-p65, and pFBD-P65-P42. These proteins were expressed using the Bac to Bac system and formulated into subunit vaccines for mouse immunization. Mouse experiments indicated that the P97R1P46 + P65-P42 protein combination elicited higher levels of specific antibodies, IL-2, IL-4, and CD8+ T cells compared to other subunit vaccine groups, a finding further validated in subsequent mouse challenge protection experiments. Therefore, we utilized the MultiBac expression system to co-express P97R1P46, P65, and P42 proteins in the pFastMultibacDual vector for immunization experiments in piglets. The piglet immunization experiments demonstrated that the Mhp subunit vaccine prepared in this study could induce specific antibodies against Mhp, with the combination of P97R1P46, P65, and P42 proteins inducing the highest level of humoral immunity. This study provides valuable insights for the development of Mhp subunit vaccines.

Developing hypoxia and lactate metabolism-related molecular subtypes and prognostic signature for clear cell renal cell carcinoma through integrating machine learning.

The microenvironment of clear cell renal cell carcinoma (ccRCC) is characterized by hypoxia and increased lactate production. However, the impact of hypoxia and lactate metabolism on ccRCC remains incompletely understood. In this study, a new molecular subtype is developed based on hypoxia-related genes (HRGs) and lactate metabolism-related genes (LMRGs), aiming to create a tool that can predict the survival rate, immune microenvironment status, and responsiveness to treatment of ccRCC patients. We obtained RNA-seq data and clinical information of patients with ccRCC from TCGA and GEO. HRGs and LMRGs are sourced from the Molecular Signatures Database. Integrating 10 machine learning algorithms and 101 frameworks, we constructed a prognostic model related to hypoxia and lactate metabolism. Its accuracy and reliability are evaluated through constructing prognostic nomograms, drawing ROC curves, and validating with clinical datasets. Additionally, risk subgroups are evaluated based on functional enrichment, tumor mutational burden (TMB), immune cell infiltration degree, and immune checkpoint expression level. Finally, we evaluate the responsiveness of risk subgroups to immunotherapy and determine personalized drugs for specific risk subgroups. 85 valuable prognostic genes were screened out. Functional enrichment analysis shows that the group with high-risk hypoxia and lactate metabolism-related genes scores (HLMRGS) is mainly involved in the activation of immune-related activities, while the low risk HLMRGS group is more active in metabolic and tumor-related pathways. At the same time, differences in the cellular functional states in the tumor microenvironment between the high risk HLMRGS group and the low risk HLMRGS group were observed. Finally, potential drugs for specific risk subgroups were determined. We have developed a novel prognostic signature that integrates hypoxia and lactate metabolism. It is expected to become an effective tool for prognosis prediction, immunotherapy and personalized medicine of ccRCC.

Key genes and biological pathways in pulmonary arterial hypertension related to endoplasmic reticulum stress identified by bioinformatics

Pulmonary arterial hypertension (PAH) is a cardiopulmonary vascular condition with an unclear pathogenesis. Targeting endoplasmic reticulum (ER) stress has been suggested as a novel treatment approach for PAH, but the mechanisms involving ER stress-related genes in PAH are not well understood. Microarray data for PAH and ER stress-related genes were analyzed. Differential and Venn analyses identified 17 differentially expressed ER stress-related genes in PAH. Candidate drugs targeting these genes were predicted using the CMap database. A protein-protein interaction (PPI) network was constructed, and hub genes (LCN2, IGF1, VCAM1, EDN1, HMOX1, TLR4) with complex interplays were identified using the STRING database and Cytoscape plugins. The clinical diagnostic performance of the hub genes was evaluated using ROC curves. The GeneMANIA website was utilized to predict enriched pathways associated with the hub genes and their functionally similar genes. MiRNAs and transcription factors (TFs) targeting the hub genes were predicted using the Networkanalyst website. The immune levels in control samples and PAH samples were assessed using various algorithms. Nine drug candidates were found to potentially target the identified ER stress-related genes. The hub genes and their correlated genes were significantly enriched in immune-related pathways. The PAH group showed increased immune cell infiltration, indicating a heightened immune response. This study sheds light on the role of ER stress-associated hub genes in PAH and proposes potential drugs targeting these genes. These findings provide valuable insights into PAH mechanisms and support the exploration of ER stress as a therapeutic target.

Discovery of key molecular signatures for diagnosis and therapies of glioblastoma by combining supervised and unsupervised learning approaches.

Glioblastoma (GBM) is the most malignant brain cancer and one of the leading causes of cancer-related death globally. So, identifying potential molecular signatures and associated drug molecules are crucial for diagnosis and therapies of GBM. This study suggested GBM-causing ten key genes (ASPM, CCNB2, CDK1, AURKA, TOP2A, CHEK1, CDCA8, SMC4, MCM10, and RAD51AP1) from nine transcriptomics datasets by combining supervised and unsupervised learning results. Differential expression patterns of key genes (KGs) between GBM and control samples were verified by different independent databases. Gene regulatory network (GRN) detected some important transcriptional and post-transcriptional regulators for KGs. The KGs-set enrichment analysis unveiled some crucial GBM-causing molecular functions, biological processes, cellular components, and pathways. The DNA methylation analysis detected some hypo-methylated CpG sites that might stimulate the GBM development. From the immune infiltration analysis, we found that almost all KGs are associated with different immune cell infiltration levels. Finally, we recommended KGs-guided four repurposable drug molecules (Fluoxetine, Vatalanib, TGX221 and RO3306) against GBM through molecular docking, drug likeness, ADMET analyses and molecular dynamics simulation studies. Thus, the discoveries of this study could serve as valuable resources for wet-lab experiments in order to take a proper treatment plan against GBM.

Tildrakizumab in the treatment of plaque psoriasis in an HIV+ patient: a case report and literature review of anti-interleukin drugs

Treatment of psoriasis associated with human immunodeficiency virus (HIV) infection is challenging due to the high incidence of comorbidities and polypharmacy and the lack of evidence on the efficacy and safety of available drugs in these patients. Therefore, clinical or anecdotal reports provide useful indications for therapy decision-making. A 64-year male with plaque psoriasis (Psoriasis Area and Severity Index=14.3) infected with HIV for 4 years, with hypercholesterolemia, hypertension, and impaired quality of life (Dermatology Life Quality Index=14) was resistant to topical therapy and acitretin. Tildrakizumab 200 mg was started, obtaining Psoriasis Area and Severity Index=0 at week 16 which was maintained after 13 months of follow-up. No adverse event was reported, and immune cell levels were unchanged. This is the first report on the treatment of psoriasis with tildrakizumab in an HIV+ patient. A literature search showed that prior to this patient, 38 HIV+ subjects had been treated with anti-cytokine agents for psoriasis.

Diversity of the immune microenvironment and response to checkpoint inhibitor immunotherapy in mucosal melanoma.

Mucosal melanoma (MucM) is a rare cancer with a poor prognosis and low response rate to immune checkpoint inhibition (ICI) compared with cutaneous melanoma (CM). To explore the immune microenvironment and potential drivers of MucM's relative resistance to ICI drugs, we characterized 101 MucM tumors (43 head and neck [H&N], 31 female urogenital, 13 male urogenital, 11 anorectal, and 3 other gastrointestinal) using bulk RNA-Seq and immunofluorescence. RNA-Seq data show that MucM has a significantly lower IFN-γ signature levels than CM. MucM tumors of the H&N region show a significantly greater abundance of CD8+ T cells, cytotoxic cells, and higher IFN-γ signature levels than MucM from lower body sites. In the subcohort of 35 patients with MucM treated with ICI, hierarchical clustering reveals clusters with a high and low degree of immune infiltration, with a differential ICI response rate. Immune-associated gene sets were enriched in responders. Signatures associated with cancer-associated fibroblasts, macrophages, and TGF-β signaling may be higher in immune-infiltrated, but ICI-unresponsive tumors, suggesting a role for these resistance mechanisms in MucM. Our data show organ region-specific differences in immune infiltration and IFN-γ signature levels in MucM, with H&N MucM displaying the most favorable immune profile. Our study might offer a starting point for developing more personalized treatment strategies for this disease.

Effects of sex and obesity on immune checkpoint inhibition-related cardiac systolic dysfunction in aged mice.

Despite accumulating data on underlying mechanisms, the influence of sex and prevalent cardio-metabolic co-morbidities on the manifestation and severity of immune checkpoint inhibitor (ICI)-induced cardiotoxicity has not been well defined. To elucidate whether sex and prevalent cardio-metabolic co-morbidities affect ICI-induced cardiotoxicity, we randomized 17-month-old male and female mice to receive control diet (CON) or high-fat diet (HFD) + L-NAME-a well-established mouse model of cardio-metabolic co-morbidities-for 17weeks (n = 5-7), and evaluated markers of T-cell function in the spleen. As expected, HFD + L-NAME significantly increased body- and heart weight, and serum cholesterol levels, and caused no systolic dysfunction, however, led to diastolic dysfunction, cardiomyocyte hypertrophy, and increased fibrosis only in males compared to corresponding CON. Western blot analyses of splenic immune checkpoint protein levels showed differential expression depending on sex and prevalent cardio-metabolic co-morbidities, suggesting T-cell exhaustion in both sexes on HFD + L-NAME, but more pronounced in males. In a sub-study with a similar setup, we tested cardiotoxic manifestations of ICI by treating mice with anti-PD-1 monoclonal antibody (ICI) for the last 2weeks of diet administration (n = 5-7). After 2weeks of ICI treatment, cardiac systolic functions significantly decreased in CON, but not in HFD + L-NAME groups of both sexes compared to baseline (before ICI administration). In conclusion, in this exploratory study using aged mice, we describe for the first time that ICI-related systolic dysfunction is diminished in both sexes when obesity and hypercholesterolemia are present, possibly due to obesity-related T-cell exhaustion.

CD1a affects the recurrence and prognosis of ovarian cancer.

Explored the correlation between CD1a expression in recurrence and prognosis of ovarian cancer (OV). The CD1a expression profile in OV, recurrent OV, and normal tissues, as well as corresponding clinical data, were obtained from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), Gene Expression Omnibus (GEO), and Genotype Tissue Expression (GTEx) databases. Meanwhile, immunohistochemical detection of CD1a expression in normal and OV tissues. Kaplan-Meier curves were plotted to estimate the hazard ratio (HR) of survival in OV. In addition, the correlation between CD1a and immune cells in OV, as well as the CD1a expression profile and corresponding survival time in pan-cancer were obtained from TCGA database. CD1a was overexpressed in OV and was significantly under-expressed in recurrent OV (TCGA-OV, p < 0.0001 and ICGC-OV, p < 0.0001). CD1a immunohistochemistry is significantly overexpressed in OV compared to normal tissue (p < 0.05). Recurrent OV (ICGC, p < 0.001; GSE17260, p < 0.001; GSE32062, p < 0.05). The prognosis in OV was significantly better when CD1a is overexpressed compared to under-expressed (HR [low], 1.426: 95% confidence interval [CI], 0.912-2.128; p = 0.050). Meanwhile, the overexpression of CD1a has a better prognosis than low expression in OV and recurrent OV (p = 0.004, HR [low] = 2.462, 95%CI [1.346-4.504] and p = 0.011, HR [low] = 2.199, 95%CI [1.202-4.024]). In addition, CD1a expression was closely correlated with immune cells, the CD8+ T cells, macrophages, and NK cells, while uncharacterized cells were significantly different (p = 2.65e-6, p = 7.52e-13, p = 8.28e-12, and p = 5.89e-8, respectively). Moreover, CD1a expression affected the prognosis in various other cancers. CD1a expression affected the recurrence and prognosis of OV and is closely related to various immune cell levels.

Rebound in epidemic control: how misaligned vaccination timing amplifies infection peaks

In this study, we explore the dynamic interplay between the timing of vaccination campaigns and the trajectory of disease spread in a population. Through modeling and comprehensive data analysis of model output, we have uncovered a counter-intuitive phenomenon: initiating a vaccination process at an inopportune moment can paradoxically result in a more pronounced second peak of infections. This “rebound” phenomenon challenges the conventional understanding of vaccination impacts on epidemic dynamics. We provide a detailed examination of how improperly timed vaccination efforts can inadvertently reduce the overall immunity level in a population, considering both natural and vaccine-induced immunity. Our findings reveal that such a decrease in population-wide immunity can lead to a delayed, yet more severe, resurgence of cases. This study not only adds a critical dimension to our understanding of vaccination strategies in controlling pandemics but also underscores the necessity for strategically timed interventions to optimize public health outcomes. Furthermore, we compute which vaccination strategies are optimal for a COVID-19 tailored mathematical model, and find that there are two types of optimal strategies. The first type prioritizes vaccinating early and rapidly to reduce the number of deaths, while the second type acts later and more slowly to reduce the number of cases; both of them target primarily the elderly population. Our results hold significant implications for the formulation of vaccination policies, particularly in the context of rapidly evolving infectious diseases.

Consensus of experts on clinical quality management for flow cytometry-based detection of lymphocyte subsets

Flow cytometry (FCM) is used to detect lymphocyte subsets and evaluate the level of cellular immunity in the body, which is one of the commonly used FCM detection projects in clinical practice. To date, numerous institutions and academic organizations, both domestically and internationally, have published guidelines and consensus documents covering various aspects, including the establishment of cytometry laboratories, standardized procedures for detecting lymphocyte subsets, and their clinical applications across different fields, each with a distinct focus. However, in clinical practice, laboratories continue to face challenges in establishing standardized quality management systems, implementing quality assurance activities, developing appropriate detection protocols and gating strategies for various scenarios, and identifying and resolving common issues encountered during detecting. Currently, there is no unified consensus on these issues. To standardize the development of quality management systems for lymphocyte subsets detecion via FCM, enhance laboratory quality management practices, and ensure the accuracy and reliability of results, the Laboratory Medicine Committee of Chinese Association of Integrative Medicine (LMC-CAIM) convened experts to formulate this expert consensus.

Evaluation of Ethanolic Extract of Red Seaweed (Gracilariopsis lemaneiformis) on Growth and Haematological Parameters of Nile Tilapia (Oreochromis niloticus)

ABSTRACTSeaweed is multicellular marine macroalgae that enhances the immunity of aquatic organisms. The study was designed to assess the ethanolic extract (EtOH) extracted from red seaweed (Gracilariopsis lemaneiformis) on Nile tilapia (Oreochromis niloticus) to evaluate growth, immunity and haematological parameters. The EtOH was applied with fish feed in four treatments such as T1‐control (0% EtOH), T2 (5% w/v EtOH), T3 (10% w/v EtOH) and T4 (15% w/v EtOH) each with three replicates. The initial average weight of the fish was 17.53 ± 2.1 g. Results showed that the growth increased gradually with the percentage of red seaweed extract, whereas the mean weight gain was found significantly higher in T4 (51.5 ± 4.2) than in the control. The specific growth rate (%) and survival rate (%) were found higher in T4 at the lowest FCR compared to other treatments (p &lt; 0.05). The blood haemoglobin level of Nile tilapia was higher in T4 (11.5 g/dL) and lowest recorded in T1 (7.5 g/dL). However, the level of blood glucose interacted inversely with blood haemoglobin. The plasma protein level was also varied among the treatments (p &gt; 0.05). The blood parameters, refractive index (RI) and spleen somatic index (SSI) were significantly different among the treatments. The RI of blood plasma and SSI were found to be better in T4 treatment. The research indicated that red seaweed extracts significantly enhanced the growth and boosted the immunity level of Nile tilapia.

Comparative study of neutralizing antibodies titers in response to different types of COVID-19 vaccines among a group of egyptian healthcare workers

BackgroundDefining the protective thresholds against the severe-acute-respiratory-syndrome-related corona virus-2 pandemic is a crucial challenge. To reduce the risks of severe disease, hospitalization, and death, various COVID-19 vaccines have been rapidly developed.Aim of the workThis study aimed to assess the impact of three common COVID-19 vaccine types; two mRNA COVID-19 vaccines: (Pfizer/BioNTech’s BNT162b2 and Moderna’s mRNA-1273), one adenoviral vector vaccine: Oxford/AstraZeneca’s ChAdOx1, and one inactivated vaccine (Sinovac Biotech/China’s Sinovac) on the level of neutralizing antibodies, considering factors such as vaccine type, demographic characteristics, and hybrid immunity. We conducted a direct comparative analysis involving 300 healthcare workers, both with and without prior SARS-CoV-2 infection (B.1, C.36.3, and AY.32 (Delta) variants). Neutralizing antibodies levels were measured at baseline (before vaccination), before the second dose, and six months after the second dose.ResultsThe results showed a significant increase in neutralizing antibodies levels after complete vaccination with all vaccine types. Among healthcare workers, those vaccinated with mRNA vaccines (Moderna or Pfizer) exhibited the highest neutralizing antibodies titers, followed by AstraZeneca, and finally Sinovac with the lowest titer. On studying the effect of previous COVID-19 infection after vaccination, no significant difference in neutralizing antibodies levels was observed between healthcare workers vaccinated with mRNA or AstraZeneca vaccines, both with prior COVID-19 infection, following the first and six months after the second dose.ConclusionThese findings suggest that individuals with prior COVID-19 may only require a single dose of mRNA or AstraZeneca vaccines to achieve a similar level of immunization as those without prior COVID-19 who completed the vaccination program.HighlightsThere is a significant increase in neutralizing antibodies levels after complete vaccination against COVID-19Vaccination with mRNA vaccines exhibits the highest neutralizing antibodies titers.Vaccination with Sinovac exhibits the lowest neutralizing antibodies titers.Graphical abstract

MFAP3L predicts tumor microenvironment status, molecular subtypes and clinical benefit in patients with bladder cancer

Bladder cancer (BLCA), ranking as the tenth most prevalent malignancy globally, imposes a substantial public health and socio-economic challenge. Despite ongoing efforts by urologists to identify novel molecular subtypes and treatment paradigms, the intrinsic heterogeneity of BLCA continues to obstruct the efficacy of current diagnostic and therapeutic evaluations, leaving a gap in the comprehensive management of BLCA. This necessitates an in-depth investigation into the BLCA tumor microenvironment (TME) to identify pivotal molecules like MFAP3L. Our research concentrated on MFAP3L, commencing with a pan-cancer analysis of its immune profile. We discovered that MFAP3L exhibits a significant negative correlation with numerous immune components and markers in BLCA, a trend not observed in other cancer types. Within the TCGA-BLCA cohort, patients were classified into High-MFAP3L and Low-MFAP3L groups according to their MFAP3L transcript levels. Our exploration into the BLCA TME delved into immune infiltration, molecular subtype patterns, and treatment preferences within these MFAP3L groups. High MFAP3L expression was linked to favorable prognoses, luminal subtypes, and low immune infiltration, inversely associated with various immune molecules and characteristics. Additionally, high MFAP3L expressors exhibited diminished immune checkpoint levels, suggesting enhanced immunotherapy tolerance and sensitivity to oncogenic pathway targeting. Conversely, low MFAP3L expression correlated with poor outcomes, basal subtypes, increased immune infiltration, and heightened gene mutation rates, alongside sensitivity to radiotherapy, EGFR-targeted treatments, and immunotherapy. Hence, MFAP3L emerges as a critical yet underexplored gene in BLCA, offering insights into immune status within the TME and aiding in molecular subtyping and therapeutic decision-making.