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Background: Notwithstanding the encouraging results of previous studies reporting on the efficiency of deep learning (DL) in COVID-19 prognostication, clinical adoption of the developed methodology still needs to be improved. To overcome this limitation, we set out to predict the prognosis of a large multi-institutional cohort of patients with COVID-19 using a DL-based model., Purpose: This study aimed to evaluate the performance of deep privacy-preserving federated learning (DPFL) in predicting COVID-19 outcomes using chest CT images., Methods: After applying inclusion and exclusion criteria, 3055 patients from 19 centers, including 1599 alive and 1456 deceased, were enrolled in this study. Data from all centers were split (randomly with stratification respective to each center and class) into a training/validation set (70%/10%) and a hold-out test set (20%). For the DL model, feature extraction was performed on 2D slices, and averaging was performed at the final layer to construct a 3D model for each scan. The DensNet model was used for feature extraction. The model was developed using centralized and FL approaches. For FL, we employed DPFL approaches. Membership inference attack was also evaluated in the FL strategy. For model evaluation, different metrics were reported in the hold-out test sets. In addition, models trained in two scenarios, centralized and FL, were compared using the DeLong test for statistical differences., Results: The centralized model achieved an accuracy of 0.76, while the DPFL model had an accuracy of 0.75. Both the centralized and DPFL models achieved a specificity of 0.77. The centralized model achieved a sensitivity of 0.74, while the DPFL model had a sensitivity of 0.73. A mean AUC of 0.82 and 0.81 with 95% confidence intervals of (95% CI: 0.79-0.85) and (95% CI: 0.77-0.84) were achieved by the centralized model and the DPFL model, respectively. The DeLong test did not prove statistically significant differences between the two models (p-value = 0.98). The AUC values for the inference attacks fluctuate between 0.49 and 0.51, with an average of 0.50 ± 0.003 and 95% CI for the mean AUC of 0.500 to 0.501., Conclusion: The performance of the proposed model was comparable to centralized models while operating on large and heterogeneous multi-institutional datasets. In addition, the model was resistant to inference attacks, ensuring the privacy of shared data during the training process., (© 2024 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Interferon epsilon (IFN-ε) belongs to the type I IFN group and exhibits various biological properties. IFN-ε exhibits different regulation mechanisms and expression via other type I IFNs. Its hormonal regulation suggests that this INF can have different functions and pathways from other type I IFNs. Although IFN-ε exhibits lower antiproliferative, anti-tumor, and antiviral activities compared to IFN-α, it has been identified to contribute to mucosal immunity, combat bacterial infections, and aid in the prevention of specific sexually transmitted diseases, such as HIV, Zika virus, etc. IFN-α and IFN-β with their well-established properties have been a research hotspot for many years; nevertheless, IFN-ε, whose unique roles are only now beginning to emerge, may be an intriguing subject for future study. This review focuses on the known activity of IFN-ε in certain cancers, pregnancy, autoimmune diseases, bacterial infections, and viruses. The aim of this paper is to enhance the understanding of the potential efficacy of IFN-ε treatment in the future., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Exosomes have emerged as a novel alternative delivery system for transporting small molecules. Tumor-derived exosomes (TEXs) possess anti-cancer properties and serve as natural carriers of microRNAs. Using this knowledge as a foundation, the current study evaluated the efficacy of delivering a miR-211 mimic via B16F10 cell-derived exosomes to block the growth and development of a melanoma cell line., Material and Methods: After exposing B16F10 cultured cells to serum-free media for 24 hours, we collected the supernatant. Subsequently, we purified the exosomes from the supernatant using a commercial kit. Scanning electron microscopy, transmission electron microscopy, dynamic light scattering, Western blot, and bicinchoninic acid protein assay were used to characterize exosomes. Following that, miR-211 mimic was loaded into exosomes (termed TEXomiR) via a modified calcium chloride procedure. The assessment of miR-211a loading efficiency into exosomes was conducted by analyzing its relative expression. MTT, annexin V/PI, and quantitative real-time polymerase chain reaction were used to measure the proliferation, apoptosis and relative expression of miR-211 target genes, respectively., Results: Our study showed that the exosomes can deliver miR-211 mimic efficiently. The treatment of B16F10 cells with miR-211-enriched TEX downregulated miR-211 target genes, including brain-specific homeobox, vascular endothelial growth factor, and transforming growth factor-β receptor. The results indicated the antiproliferative effect of TEXomiR as time-dose-dependent. The flow cytometry evaluation showed that TEXomiR could induce the apoptosis of B16F10 cells., Conclusions: Our data indicated that exosomes can be suitable carriers for miR-211 mimic. Moreover, TEXomiR via anti-cancer effects could inhibit the progression of melanoma cancer., Competing Interests: None., (Copyright © 2024 Termedia.)

The aim of this study was to evaluate antibody response against influenza vaccine in beta thalassemia major patients from Iran. Thirty beta thalassemia major patients were enrolled and divided into three groups: single dose (group 1), double dose (group 2), and control (group 3). Seroconversion, seroprotection, and geometric mean titer (GMT) assays were performed through hemagglutination inhibition (HI) on days 0, 14, and 60. Based on the results, the level of antibody titer was increased in group 2. Two weeks after vaccination, seroconversion rate was about 20% and 30% in groups 1 and 2. Sixty days after vaccination, the seroconversion rate was around 70% and GMT showed a more than 2-fold increase in group 2. Based on the results, the immunogenicity of double dose vaccination against influenza infection appears to be higher than the single dose vaccine in beta thalassemia major patients, and thus it is recommended to use two doses of vaccine, especially in splenectomized patients who are more sensitive than others., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: We aimed to analyze the prognostic power of CT-based radiomics models using data of 14,339 COVID-19 patients., Methods: Whole lung segmentations were performed automatically using a deep learning-based model to extract 107 intensity and texture radiomics features. We used four feature selection algorithms and seven classifiers. We evaluated the models using ten different splitting and cross-validation strategies, including non-harmonized and ComBat-harmonized datasets. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were reported., Results: In the test dataset (4,301) consisting of CT and/or RT-PCR positive cases, AUC, sensitivity, and specificity of 0.83 ± 0.01 (CI95%: 0.81-0.85), 0.81, and 0.72, respectively, were obtained by ANOVA feature selector + Random Forest (RF) classifier. Similar results were achieved in RT-PCR-only positive test sets (3,644). In ComBat harmonized dataset, Relief feature selector + RF classifier resulted in the highest performance of AUC, reaching 0.83 ± 0.01 (CI95%: 0.81-0.85), with a sensitivity and specificity of 0.77 and 0.74, respectively. ComBat harmonization did not depict statistically significant improvement compared to a non-harmonized dataset. In leave-one-center-out, the combination of ANOVA feature selector and RF classifier resulted in the highest performance., Conclusion: Lung CT radiomics features can be used for robust prognostic modeling of COVID-19. The predictive power of the proposed CT radiomics model is more reliable when using a large multicentric heterogeneous dataset, and may be used prospectively in clinical setting to manage COVID-19 patients., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Coronaviruses (CoVs) were first discovered in the 1960s. Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) has been identified as the cause of COVID-19, which spread throughout China and subsequently, across the world. As COVID-19 causes serious public health concerns across the world, investigating the characteristics of SARS-CoV-2 and its interaction with the host immune responses may provide a clearer picture of how the pathogen causes disease in some individuals. Interestingly, SARS-CoV-2 has 80% sequence homology with SARS-CoV-1 and 96-98% homology with CoVs isolated from bats. Therefore, the experience acquired in SARS and Middle East Respiratory Syndrome (MERS) epidemics may improve our understanding of the immune response and immunopathological changes in COVID-19 patients. In the present paper, we have reviewed the immune responses (including the innate and adaptive immunities) to SARS-CoV, MERS-CoV, and SARS-CoV-2, so as to improve our understanding of the concept of the COVID-19 disease, which will be helpful in developing vaccines and medications for treating the COVID-19 patients., (© 2021 S. Karger AG, Basel.)

Cancer stem cells (CSCs) have critical roles in tumor development, progression, and recurrence. They are responsible for current cancer treatment failure and remain questionable for the design and development of new therapeutic strategies. With this issue, medical imaging provides several clues for finding biological mechanisms and strategies to treat CSCs. This review aims to summarize current molecular imaging approaches for detecting CSCs. In addition, some promising issues for CSCs finding and explaining biological mechanisms have been addressed. Among the molecular imaging approaches, modalities including Magnetic resonance imaging (MRI) and positron emission tomography (PET) have the greatest roles and several new approaches such as optical imaging are in progress., (© 2020 Iran University of Medical Sciences.)

Metabolic abnormalities such as dyslipidemia, hyperinsulinemia, or insulin resistance and obesity play key roles in the induction and progression of type 2 diabetes mellitus (T2DM). The field of immunometabolism implies a bidirectional link between the immune system and metabolism, in which inflammation plays an essential role in the promotion of metabolic abnormalities (e.g., obesity and T2DM), and metabolic factors, in turn, regulate immune cell functions. Obesity as the main inducer of a systemic low-level inflammation is a main susceptibility factor for T2DM. Obesity-related immune cell infiltration, inflammation, and increased oxidative stress promote metabolic impairments in the insulin-sensitive tissues and finally, insulin resistance, organ failure, and premature aging occur. Hyperglycemia and the subsequent inflammation are the main causes of micro- and macroangiopathies in the circulatory system. They also promote the gut microbiota dysbiosis, increased intestinal permeability, and fatty liver disease. The impaired immune system together with metabolic imbalance also increases the susceptibility of patients to several pathogenic agents such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Thus, the need for a proper immunization protocol among such patients is granted. The focus of the current review is to explore metabolic and immunological abnormalities affecting several organs of T2DM patients and explain the mechanisms, whereby diabetic patients become more susceptible to infectious diseases., (Copyright © 2020 Daryabor, Atashzar, Kabelitz, Meri and Kalantar.)

Cancer stem cells (CSCs), also known as tumor-initiating cells (TICs), are elucidated as cells that can perpetuate themselves via autorestoration. These cells are highly resistant to current therapeutic approaches and are the main reason for cancer recurrence. Radiotherapy has made a lot of contributions to cancer treatment. However, despite continuous achievements, therapy resistance and tumor recurrence are still prevalent in most patients. This resistance might be partly related to the existence of CSCs. In the present study, recent advances in the investigation of different biological properties of CSCs, such as their origin, markers, characteristics, and targeting have been reviewed. We have also focused our discussion on radioresistance and adaptive responses of CSCs and their related extrinsic and intrinsic influential factors. In summary, we suggest CSCs as the prime therapeutic target for cancer treatment., (© 2019 Wiley Periodicals, Inc.)

Competing Interests: None

The innate immune system is the first line of defense against microbial pathogens. The response of innate immunity is initiated by molecules known as pattern recognition receptors (PRRs). Such responses are often triggered by nucleic acids that are delivered to the cytoplasm or nucleus of cells. The ability to recognize foreign nucleic acids in these two locations is an important defense mechanism of the human innate immune system. Several PRRs are located in the cytosol or nucleus and detect foreign DNAs. The pyrin and hematopoietic interferon-inducible nuclear (PYHIN) domain protein is a family of PRRs that includes interferon-inducible protein 16, absent in melanoma 2, PYHIN 1 (or interferon-inducible protein X, as it is also known), myeloid cell nuclear differentiation antigen, and pyrin domain only protein 3. These nuclear and cytosolic sensors play an essential part in host defense of intracellular pathogens. In addition, members of the PYHIN family are critical regulators of immune response, apoptosis, cell growth, differentiation, and transcription. In this review, we summarize important characteristics of these innate immune sensors and their roles in several diseases. A better understanding of the role of DNA sensors in the nucleus and cytoplasm will lead to the development of novel therapeutic approaches to control infections and associated diseases.

Asthma prevalence and severity are greater in women than in men, and mounting evidence suggests this is in part related to female steroid sex hormones. Conflicting data are reported regarding pro- and anti-inflammatory properties of estradiol. This study was designed to clarify whether estradiol may contribute to enhanced T helper (Th) 17-associated cytokines production by peripheral blood mononuclear cells (PBMC) in asthmatic patients and healthy individuals. PBMCs from patients with asthma and healthy donors were cultured with 17-β estradiol (E2) and phytohemagglutinin (PHA). The quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure IL-6, IL-17, IL-23 and TGF-β. We observed a significant increased IL-17, IL-23 and TGF-β expression in PBMCs of patients compared to the healthy individuals. In addition, our findings indicated that IL-6 and IL-17 expressions in PBMCs were induced, following E2 treatment. Our results identified an impact of E2 in stimulation of Th17 phenotype, and upon hormonal oscillations and hormone replacement therapy (HRT), asthma inflammation may be mediated by Th17-associated cytokines.

Background and Objectives: Mesenchymal stem cells (MSCs) are multipotent adult stem cells with immunomodulatory properties. The mechanisms by which MSCs inhibit the proliferation of pro-inflammatory T cells have not been fully elucidated yet. It is assumed that pro-inflammatory T-cells play an important role in the development of autoimmune diseases. We investigated the potential therapeutic effects of human adipose tissue derived (Ad)-MSCs on the peripheral blood mononuclear cells (PBMCs) of rheumatoid arthritis (RA) patients and healthy individuals, with a particular focus on Th17-associated cytokines., Materials and Methods: PBMCs from RA patients and healthy donors were co-cultured with Ad-MSCs and HeLa with or without Phytohemagglutinin (PHA). Finally, IL-6, IL-17, IL-21, IL-23 and TGF-β levels were determined by ELISA and quantitative real-time RT-PCR on co-culture supernatants and PBMCs, respectively., Results: In co-culture interaction, Ad-MSCs inhibited IL-17 secretion by PBMCs compared to unstimulated PBMCs cultured alone. In addition, IL-21 expressions in PBMCs of the patient group, and IL-17 and IL-21 in healthy group were inhibited by Ad-MSCs compared to PBMCs cultured alone. TGF-β expression in healthy individuals remarkably increased in both MSC-treated groups with and without PHA in comparison to PHA-stimulated and -unstimulated PBMCs., Conclusions: This study demonstrates that human Ad-MSCs act as key regulators of immune tolerance by inhibiting the inflammation. Therefore, they can be attractive candidates for immunomodulatory cell-based therapy in RA., (Copyright © 2017. Published by Elsevier B.V.)

Background: Type 1 diabetes (T1D) is thought to involve chronic inflammation, which is manifested by the activation and expression of different inflammatory mediators. Th1- and Th17-associated cytokines are factors that have been shown to exert profound pro-inflammatory activities and have been implicated in the pathogenesis of T1D in mice and humans., Objectives: Therefore, the aim of this case control study was to determine the serum level of IL-17, IL-21, IL-27, transforming growth factor beta (TGF-β), and IFN-γ and their reciprocal relationship in Iranian T1D patients., Patients and Methods: Blood samples were collected from 48 T1D patients and 49 healthy individuals with no history of malignancies or autoimmune disorders based on simple sampling. The serum levels of IL-17, IL-21, IL-27, TGF-β, and IFN-γ were measured by the enzyme linked immunosorbent assay (ELISA)., Results: The serum levels of IL-17 and IL-21 were significantly higher in T1D patients compared to the healthy individuals (p = 0.005 and 0.01, respectively), but interestingly, the opposite was the case for IL-27 (p < 0.0001). However, there were no significant differences in TGF-β and IFN-γ between both groups. In addition, IL-17/IFN-γ and IL-17/IL-27 ratios were higher in patients compared to the control group., Conclusions: Our results indicated dominant Th17-associated IL-17, suggesting a shift from the Treg and Th1 phenotypes toward the Th17 phenotype. Therefore, it can promote inflammation in β cells in T1D. In addition, it suggests the role of Th17 and Th17/Th1 ratios as a potential contributor to β cells destruction and the Th17/Th1 response ratio may provide a novel biomarker for rapid T1D diagnosis before the destruction of β cells and progression of the disease to the clinical end stages.

Introduction: Depression is a mental disorder that highly associated with immune system. Therefore, this study compares the serum concentrations of IL-21, IL-17, and transforming growth factor β (TGF-β) between patients with major depressive disorder and healthy controls., Methods: Blood samples were collected from 41 patients with major depressive disorder and 40 healthy age-matched controls with no history of malignancies or autoimmune disorders. The subjects were interviewed face to face according to DSM-IV diagnostic criteria. Depression score was measured using completed Beck Depression Inventory in both groups. The serum concentrations of IL-21, IL-17, and TGF-β were assessed using ELISA., Results: The mean score of Beck Depression score in the patient and control groups was 35.4±5.5 and 11.1±2.3. IL-17 serum concentrations in the patients and the control group were 10.03±0.6 and 7.6±0.6 pg/mL, respectively (P=0.0002). TGF-β level in the patients group was significantly higher than compare to the control group; 336.7±20.19 vs. 174.8±27.20 pg/mL, (P<0.0001). However, the level of IL-21 was not statistically different between the two groups 84.30±4.57 vs. 84.12±4.15 pg/mL (P>0.05)., Conclusion: Considering pro-inflammatory cytokines, current results support the association of inflammatory response and depressive disorder. So, it seems that pro-inflammatory factors profile can be used as indicator in following of depression progress and its treatment impacts.

Interleukin (IL)-17-producing CD4(+) T helper (Th17) cells that are known to produce IL-17 have recently been defined as a unique subset of proinflammatory helper cells. Interleukin 17 is an inflammatory cytokine with robust effects on many cells. It can play important roles in the pathogenesis of diverse groups of immune-mediated diseases. In this regard, the present case-control study aimed at determining serum levels of IL-17, IL-6, and transforming growth factor β (TGF-β) in Iranian breast cancer patients. Blood samples were collected from 55 patients with breast cancer and 34 healthy individuals with no history of malignancies or autoimmune disorders, based on simple sampling. The serum levels of IL-17, IL-6 and TGF-β were measured by enzyme-linked immunosorbent assay (ELISA). The serum level of IL-6 was significantly lower in patients with breast cancer compared with healthy individuals (p = 0.0003), and also the IL-17 was lower in the patient group than in controls (p = 0.01). Interestingly, the TGF-β serum level in patients was less than in controls (p < 0.0001). As most of the cases investigated in this study were in their early stages, it can be concluded that reduced IL-17, IL-6, and TGF-β can be used as predictors for clinical stage and prognosis of cancers such as breast carcinoma.