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Abstract Non-Hodgkin lymphomas (NHLs) are heterogeneous and are among the most common hematological malignancies worldwide. Despite the advances in the treatment of patients with NHLs, relapse or resistance to treatment is anticipated in several patients. Therefore, novel therapeutic approaches are needed. Recently, natural killer (NK) cell-based immunotherapy alone or in combination with monoclonal antibodies, chimeric antigen receptors, or bispecific killer engagers have been applied in many investigations for NHL treatment. The functional defects of NK cells and the ability of cancerous cells to escape NK cell-mediated cytotoxicity within the tumor microenvironment of NHLs, as well as the beneficial results from previous studies in the context of NK cell-based immunotherapy in NHLs, direct our attention to this therapeutic strategy. This review aims to summarize clinical studies focusing on the applications of NK cells in the immunotherapy of patients with NHL.

Self-regulating is a set of processes that controls or alters individuals' behavior, emotion, and performance. We aimed to evaluate the relation between three components of self-regulating including integrative self-knowledge, mindfulness, self-control, and some variables of mental health and self-conscious emotions. Methods: A total of 233 Iranian university students voluntarily enrolled in the study. Seven questionnaire forms including Integrative Self-Knowledge Scale (ISKS), Attention Awareness Scale (MASS), Short Self Control Scale (SSCS), Costello & Comrey's Anxiety and Depression Scale, Rosenberg Self-Esteem Scale (RSES), Authentic Pride Scale (APS), and other as sham scale (OAS) were distributed to participants. The correlation between self-regulating variables, mental health, and self-conscious emotions were analyzed using Pearson's correlation coefficient test. Results: We found a negative correlation between self-regulating variables, depression, and anxiety. Our data also revealed that self-esteem positively related to integrative self-knowledge, mindfulness, and self-control. Among self-conscious emotions variables, authentic pride had a positive correlation with self-regulating variables whereas feelings of shame appeared a negative relationship with them. Conclusion: Integrative self-knowledge, mindfulness, and self-control as self-regulating components correlated to mental health and self-conscious emotions.

Background & Aims: Bone marrow transplantation (BMT) is a curative treatment for various hematological malignancies. In standard survival models, the possibility of a cure has not been considered. Mixture cure models, which account for the possibility of a cure, can provide valuable insights into patient outcomes. The purpose of this study was to apply a smooth semi-nonparametric analysis for the mixture cure model to determine risk factors for survival and effective factors for the cure in bone marrow transplant patients. Materials & Methods: Data from BMT patients treated at Taleghani Hospital in Tehran were analyzed using a Weibull mixture cure model and an accelerated failure time mixture cure (AFTMC) model with an exponential kernel. The goodness-of-fit of each model was assessed using Akaike's information criterion (AIC). Results: The Weibull mixture cure model indicated that non-Hodgkin's lymphoma and acute leukemia were significantly associated with time to death. Age, recurrence after transplant, and hemoglobin levels were associated with the cure probability. The AFTMC model confirmed the prognostic effects of age, non-Hodgkin's lymphoma, and acute leukemia on time to death and further revealed that age and recurrence after transplant also influenced the cure probability. Conclusion: The smooth semi-nonparametric approach to mixture cure models provides a comprehensive analysis of BMT patient outcomes, identifying both prognostic and curative factors. This information can guide treatment decisions and improve patient survival.

Introduction: Chimeric Antigen Receptor (CAR) T cells have tremendous potentials for cancer treatment; however, various challenges impede their universal use. These restrictions include the poor function of T cells in tumor microenvironments, the shortage of tumor-specific antigens and, finally, the high cost and time-consuming process, as well as the poor scalability of the method. Creative gene-editing tools have addressed each of these limitations and introduced next generation products for cell therapy. The clustered regularly interspaced short palindromic repeats-associated endonuclease 9 (CRISPR/Cas9) system has triggered a revolution in biology fields, as it has a great capacity for genetic manipulation. Method: In this review, we considered the latest development of CRISPR/Cas9 methods for the chimeric antigen receptor T cell (CAR T)-based immunotherapy. Results: The ability of the CRISPR/Cas9 system to generate the universal CAR T cells and also potent T cells that are persistent against exhaustion and inhibition was explored. Conclusion: We explained CRISPR delivery methods, as well as addressing safety concerns related to the use of the CRISPR/Cas9 system and their potential solutions.

Abstract Aim Candidates of Hematopoietic Stem Cell Transplantation (HSCT) may be at nutritional risk due to decreased oral intake, high nutritional requirements and nutrient malabsorption. The aim of this study was to evaluate the association between nutritional status and blood biomarkers in candidates of HSCT. Methods A total of 278 patients aged 18–65 years old were recruited and their baseline demographic and clinical characteristics were recorded. All subjects underwent nutritional status analysis using Nutritional Risk Screening (NRS-2002). Blood biomarkers including C-reactive protein (CRP), Erythrocyte Sedimentation Rate (ESR), hemoglobin, albumin and total protein as well as CRP-albumin ratio (CAR) and Body Mass Index (BMI) were measured and compared between two groups based on Nutritional Risk Screening (NRS-2002) within 24 h of admission in Bone Marrow Transplant ward. Results The results showed that undernourished patients (NRS ≥ 3) had significantly higher inflammatory markers including ESR, CRP and CAR as well as lower BMI and serum albumin and hemoglobin concentrations (P 0.05). Conclusions This study revealed that BMI combined with biochemical markers are the appropriate parameters for assessment of nutritional status in HSCT candidates. Furthermore, the nutritional status was verified to be significantly associated with systematic inflammation.

Hematopoietic stem cell transplantation (HSCT) is a life-saving therapy for various hematologic disorders. Due to the bone marrow suppression and its long recovery period, secondary infections, like cytomegalovirus (CMV), Epstein-Bar virus (EBV), and adenovirus (AdV), are the leading causes of morbidity and mortality in HSCT cases. Drug resistance to the antiviral pharmacotherapies makes researchers develop adoptive T cell therapies like virus-specific T cell therapy. These studies have faced major challenges such as finding the most effective T cell expansion methods, isolating the expected subtype, defining the functionality of the end-cell population, product quality control, and clinical complications after the injection. This review discusses the viral infections after HSCT, T cells characteristics during chronic viral infection, application of virus-specific T cells (VSTs) for refractory infections, standard methods for producing VSTs and their limitation, clinical experiences on VSTs, focusing on outcomes and side effects that can be helpful in decision-making for patients and further researches.

Background: Allogenic hematopoietic stem cell transplantation is considered as an effective treatment for patients with acute myeloid leukemia. However, complications of transplantation, like aGVHD, affect the efficiency of allogenic hematopoietic stem cell transplantation. The present study aimed to implement different models of data mining (DM) (single and ensemble) for prediction of allogenic hematopoietic stem cell transplantation in patients with acute myeloid leukemia (transplantation against host disease). Method: We conducted this developmental study on 94 patients with 34 attributes in Taleghani Hospital, Tehran, Iran, during 2009–2017. In this practical study, data were analyzed via decision tree (DT) algorithms, including decision tree, random forest and gradient boosting (ensemble learning), artificial neural network (Single Learning), and support vector machine. Some criteria, like specificity, accuracy, Fmeasure, AUC (area under curve), and sensitivity, were reported in order to evaluate DT algorithms. Results: There were 34 transplantation-related variables; some predictors, such as liver, hemoglobin, and donor blood group, were found to be the most important ones. To predict aGVHD, the two selected algorithms included the most appropriate DM models, artificial neural network and support vector machine classifiers, with ROC of 100. Conclusion: This study indicated that DT algorithms could be successfully used for approving the efficiency of the models predicting allogenic hematopoietic stem cell transplantation.

Abstract Background Relapse is a frequent occurrence in autologous hematopoietic stem cell transplantation (AHSCT), and early relapse after AHSCT results in poor survival and low quality of life. Predictive marker determination for AHSCT outcomes could be helpful in the prevention of relapse through personalized medicine. Here the predictive value of circulatory microRNAs (miRs) expression for AHSCT outcomes was studied. Methods 50 MM and lymphoma candidates for AHSCT participated in this study. Two plasma samples were obtained before AHSCT from each candidate; one before mobilization and the other after conditioning. Extracellular vesicles (EVs) were isolated by ultracentrifugation. miR-125b, miR-126, miR-150, and miR-155 expression were analyzed in both plasma and EVs using real time polymerase chain reaction analysis. Other data related to AHSCT and its outcomes were also collected. The predictive value of miRs and other factors for outcomes was assessed by multi-variant analysis. Results By 90 weeks follow up after AHSCT, multi-variant and ROC analysis showed miR-125b as a predictive marker for relapse, high lactate dehydrogenase (LDH), and high erythrocyte sedimentation rate (ESR). The cumulative incidence of relapse, high LDH, and high ESR increased with an increase in circulatory miR-125b expression. Conclusion miR-125b could be applicable in prognosis evaluation and also create a possible new targeted therapy opportunity for enhanced outcomes and survival after AHSCT. Trial registration The study was retrospectively registered. Ethic code No: IR.UMSHA.REC.1400.541.

Objective: Natural killer (NK) cells are critical immune cells for acute myeloid leukemia (AML) targeting. However,little is known about the relationship between using checkpoint inhibitors and heat shock protein 70 (Hsp70) as NK cellactivators to control AML. Therefore, the study aims to find the best formulation of Hsp70, human PD-1 (Programmedcell death protein 1) blocker, and interleukin 15 (IL-15) to activate NK cells against AML.Materials and Methods: In this experimental study, the NK cells were isolated from mononuclear cells (MNCs) byusing magnetic activation cell sorting (MACS) and were activated using the different combinations of Hsp70, PD-1blocker, and IL-15 and then followed by immunophenotyping, functional assays to estimate their killing potential, andevaluation of expression pattern of PRF1, PIK3CB, PD-1, AKT-1, FAS-L, TRAIL, and GER A and B.Results: The expression of PD-1 was significantly (P

Background: Hodgkin lymphoma (HL) is one of the best curable malignancies. Randomized controlled studies have validated the benefit of hematopoietic stem cell transplant (HSCT) for patients with relapsed or primary refractory HL. This analysis aimed to identify significant prognostic factors on the recurrence of the disease after HSCT applying a cure rate model.Method: In this retrospective cohort study, there were 92 patients with HL who underwent HSCT from 2007 to 2014 with 18 months of follow-up in Tehran, Iran. The survival time was set as the time interval between transplantation and the recurrence of HL. In addition, we utilized hyper-Poisson distribution as discrete frailty to account the unobserved heterogeneity and random effects.Results: In non-cured cases, the mean of survival time was 318 (95% confidence interval, 144-493) days. The 1-, 3-, and 5-year survival rates were 88.9%, 83.4%, and 80.7%, respectively. A significant association was observed between the cured patients and the variables such as age, the experience of pre-transplantation relapse, hemoglobin (Hb), mononuclear cells (MNCs), and body surface area (BSA) at the time of transplantation.Conclusion: The study concluded that less than 30 years of age, a high level of Hb (g/dl), a low level of MNCs and BSA (m2), and the absence of pre-transplantation experience of relapse were associated with better survival following HSCT. Based on this study, post-transplant consolidation therapies could be considered for the treatment of HL patients after HSCT.

Introduction: The mixed effects logistic regression model is a common model for analysing correlated binary data as longitudinal data. The between and within subject variances are typically considered to be homogeneous but longitudinal data often show heterogeneity in these variances. This study proposes a Bayesian mixed effects location scale model to accommodate heteroscedasticity in binary data analysis. Methods: This study was carried out in two stages; first, the simulation study was used to evaluate the accuracy of the proposed model with the Bayesian approach and then the proposed model was applied to a real data. In simulation study, the data were generated from the mixed effects location scale model with different correlations between the random location effect and random scale effect and different sample sizes. In order to evaluate the accuracy of the estimations, the Root Mean Square Error, bias and Coverage Probability were calculated and the deviance information criterion was used to select the appropriate model. At the end we utilized this model to analyse uric acid levels of patients with haematological disorders. Results: The simulation results show the accuracy of model parameter estimates as well as the correlation between random location and scale effects. They also display that if a random scale effect is present in the data, it should be accounted for in model. Otherwise, the model is forced to assign the within subject variation due to these subject random effects to the error term. The results of real data are also in line with this. The odds of having normal UA levels increases by a factor of 26% per week. Due to the positive value of the covariance parameter, patients with higher mean of UA levels show higher variation in UA levels. Furthermore, the significance of the covariates in the between subject and within subject variances model, as well as the significance of the random scale variance determines the heterogeneity across subjects. Conclusion: Bayesian mixed effects location scale model provides a useful tool for analysing correlated binary data with heteroscedasticity because it considers data correlation and modelling mean and variance simultaneously. Furthermore, it improves the accuracy of statistical inference in longitudinal studies compared to classic mixed effects models.

Objective: Different Cell Culture medias can affect the expansion of T cells. The aim of this study is to assess signaling pathways, protein interactions and genes in T cells cultured in different common T cell expansion medias to select the best candidate. Materials and Methods: In this in silico observational study, with the use of bioinformatics analysis and the use of enrichment databases, gene expression profiles were investigated using microarray analysis. Results: The results of this study were the joint selection of 26 upregulated genes and 59 downregulated genes that were involved in SREBP control of lipid synthesis, co-stimulatory signal during T-cell activation mitosis and chromosome dynamics, telomeres, telomerase, and cellular aging signal pathways. Conclusion: Using bioinformatics analyzes, integrated and regular genes were selected as common genes CD80, LST1, ATM and ITM2B 4-1BBL, Akt inhibitor, interleukin 7 and 15 expansion media.

Data describing physicians’ and patients’ perspectives towards immune thrombocytopenia (ITP) management and impact of disease in Iran are limited. This ITP World Impact Survey was conducted between October 2019 and October 2020. Of the 114 patients included in the survey, 17 were aged ≤18 years. Forty-seven physicians, including 22 pediatric hematologists, participated in the survey. Fatigue and anxiety around stable platelet counts were frequent patient-reported symptoms at diagnosis and at survey completion. According to physicians, “watch-and-wait” was the preferred treatment option for mean (standard deviation) proportion of 50.1 (24.1) and 48.6 (21.8) of their adult and pediatric patients, respectively, following first diagnosis. Per adult and pediatric hematologists, the most prescribed treatments for newly diagnosed patients based on available answers were steroids (100%, n = 20/20; 89%, n = 16/18), respectively. Forty percent of adult (n = 10/25) and 38% of pediatric hematologists (n = 8/21) reported that ITP reduced patients’ quality of life. Energy levels (46%, n = 52/112) and ability to concentrate on everyday activities (42%, n = 47/113) were the most affected aspects of patients' lives. This I-WISh study in Iran underlined the negative impact of ITP on patients.

Background: In December 2019, pneumonia associated with a novel coronavirus (COVID-19) was reported in Wuhan, China. Acute respiratory distress syndrome (ARDS) is the most frequently observed complication in COVID-19 patients with high mortality rates. Objective of study: To observe the clinical effect of plasmapheresis on excessive inflammatory reaction and immune features in patients with severe COVID-19 at risk of ARDS. Materials and methods: In this single-center study, we included 15 confirmed cases of COVID-19 at Masih Daneshvari Hospital, in March 2020 in Tehran, Iran. COVID-19 cases were confirmed by RT-PCR and CT imaging according to WHO guidelines. Plasmapheresis was performed to alleviate cytokine-induced ARDS. The improvement in oxygen delivery (PaO2/FiO2), total number of T cells, liver enzymes, acute reaction proteins, TNF-α and IL-6 levels were evaluated. Results: Inflammatory cytokine levels (TNF-α, IL-6), and acute phase reaction proteins including ferritin and CRP were high before plasmapheresis. After plasmapheresis, the levels of PaO2/FiO2, acute phase reactants, inflammatory mediators, liver enzymes and bilirubin were significantly reduced within a week (p

Background: Graft-versus-host disease (GVHD) is a life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Identifiying the probable risk factors can help the clinicians manage the consequences of GVHD. The main aim of this study was to analyze the correlation of body mass index (BMI) as a risk factor with the GVHD incidence.Methods: This retrospective study was conducted on 199 patients who received allo-HSCT during 2007-2017, as well as their donors. Almost all included patients received 10/10 human leukocyte antigen )HLA(-matched allogeneic stem cell transplants. The clinical data, including BMI, underlying disease and GVHD incidence, were collected from the clinical records.Results: In the present study, GVHD was seen in 77 (38.6%) patients, including 59 acute and 18 chronic GVHD. The most frequent BMI range in both donors (35.5%) and recipients (45.2%) was between 18.5- 24.9 kg/m2. The transplants in which the BMI of donors were below 18.5 kg/m2 had 58% lower odds of GVHD incidence, compared to those with obese donors (CI: [0.21-0.85]; P = 0.05). Conversely, the donors with a BMI between 18.5 and 24.9 kg/m2 led to a 19% higher odds of GVHD incidence, especially acute GVHD, than transplants from donors with BMI above 30 kg/m2 (CI: [0.68-2.09]; P = 0.09). The recipients with a BMI between 18.5 and 24.9 kg/m2 had the odds of GVHD incidence 63% more than those with a BMI above 30 kg/m2 (CI: [0.89-3.06]; P= 0.3).Conclusions: The findings of the present study suggest the donor's BMI as a probable GVHD risk factor so that the BMI lower than 18.5 kg/m2 was statistically correlated with a decreased incidence of GVHD.

Background: Several reports have associated the severe Coronavirus disease-2019 (sCOVID-19) with secondary-hemophagocytic lymphohistiocytosis (sHLH) and proposed utilizing the hemophagocytic syndrome diagnostic score (HScore) for sCOVID-19 patients. We conducted a systematic review and meta-analysis to find the possible association of HScore parameters with severity in COVID-19 patients. Methods: A systematic search was performed in Medline via PubMed, EMBASE, and Cochrane databases using all HScore and COVID-19 keywords. The studies were all from 2020, and the study language was limited to English. The records were screened based on inclusion/exclusion criteria. Random/fixed-effect models were employed for meta-analysis, based on the I2 index of parameters. The pooled mean differences were estimated for continuous parameters. The pooled odds-ratio was estimated for fever. The level of significance was set at 0.05.Results: Eighteen studies (comprising 2459 patients) out of 26151 screened studies were included in this meta-analysis. The results showed that the level of leukocyte, neutrophil, aspartate transaminase (AST), ferritin, and fibrinogen were significantly higher in sCOVID-19 patients than in non-severe ones. Significant lower levels of lymphocyte, platelet, and hemoglobin were also found in sCOVID-19 patients than non-severe patients. Fever was nearly associated with two times increased odds of sCOVID-19 (P=0.051).Conclusion: Lymphopenia, thrombocytopenia, hypohemoglobinemia, hyperferritinemia, high levels of AST, and fever are common features of both sCOVID-19 and HLH. However, the leukocytosis, neutrophilia, and hyperfibrinogenemia found in sCOVID-19 are in contrast with HScore. Conclusively, HScore parameters could be risk factors for sCOVID-19. However, some parameters’ roles are contradictory, suggesting the need for further investigation and a new way of HScore interpretation in sCOVID-19 patients.A preprint of this study was published at https://www.researchsquare.com/article/rs-54490/v2.

Purpose: Mesenchymal stem cells (MSCs) have immunomodulatory traits making them a promising choice in the treatment of inflammatory diseases such as graft-versus-host disease (GVHD). Tumor necrosis factor-alpha (TNFα) is a major player of inflammatory disease which is blocked by infliximab to reduce the inflammation. The present study aims to assess the infliximab effects on the anti-inflammatory properties of MSCs. Methods: In this study, bone marrow mesenchymal stem cells (BMMSCs) were co-cultured with peripheral blood mononuclear cells (PBMCs) of GVHD patients in the presence of 10, 20 and 30 µg/mL of infliximab for 48 and 72 hours. The mRNA expression of indoleamine-2,3- dioxygenase (IDO) and inducible nitric oxide synthase (iNOS), as well as the secreted amount of prostaglandin E2 (PGE2) in the culture supernatant, were examined. Results: The results of this study show that the expression of IDO and iNOS genes, as well as the secretion amount of PGE2 in co-cultured groups raised dramatically, compared to the culture of BMMSCs or PBMCs alone. In co-culture groups containing infliximab, the expression of IDO and iNOS and also the amount of released PGE2 was significantly decreased compared to the control group without infliximab. However, no difference was found in the expression of assayed factors between 48 and 72 hours of treatments. Conclusion: As an anti-TNFα agent, infliximab can decrease the inflammation in the microenvironment of MSCs, which might mitigate the immunomodulatory effects of MSCs. These effects of anti-inflammatory agents on the immunomodulatory capacity of MSCs should be considered in MSC therapy.

Background: Autologous hematopoietic stem cell transplantation (auto-HSCT) has become an effective treatment for a wide range of hematologic and non-hematologic diseases. Patients undergoing HSCT might require multiple platelets and red blood cell (RBC) transfusions during aplasia phase until engraftment, which could profoundly affect patients’ conditions. Identification of risk factors associated with blood product requirements could help in decreasing transfusion-related complications. We evaluated the association of disease type, pre-transplant hemoglobin level, and pre-transplant platelet count with RBC/platelet transfusion requirement after auto-HSCT. Methods: In this retrospective study, 324 patients diagnosed with multiple myeloma (MM), Hodgkin disease (HD), and non-Hodgkin lymphoma (NHL) and underwent auto-HSCT were included. The associations of disease type, pre-transplant hemoglobin level, and platelet count with post-transplant packed cell and single-/random-donor platelet transfusions were evaluated. Results: Our study results illustrated that the higher pre-transplant hemoglobin level significantly decreased the post-HSCT requirement for packed cell (IRR=0.81, [CI: 9.73-0.90], P=0.0001), while the pre-transplant platelet showed no significant relationship with platelet requirement after HSCT. HD was associated with increment in packed cell (IRR=2.04, [CI: 1.35-3.08], P=0.001) and single donor platelet (IRR=1.39, [CI: 1.09-1.78], P=0.008) requirement after transplant. The trends showed that a higher platelet level led to a lower need for platelet transfusion. Conclusion: Pre-transplant hemoglobin level could be valuable markers for predicting post-HSCT RBC requirements and might be beneficial for better management of transfusion requirements to minimize the transfusion-related complications. Patients with HD seem to be more prone to blood product requirements post-transplant.

Background and purpose: Several studies investigated the role of C-reactive protein (CRP) during transplantation and inflammation, and clinical outcomes after stem cell transplantation. In this study, we examined the relationship between the earliest CRP level on admission day, and the first outcome after transplantation, myeloid and platelet engraftment, and the length of hospitalization in patients with Autologous hematopoietic stem cell transplantation (Auto-HSCT). Materials and methods: In this retrospective study, using clinical records from 2014-2020, information including patients’ demographic characteristics, CRP levels on admission day, white blood cell, and platelet counts were investigated. Engraftment day and duration of hospitalization were also recorded. To analyze the data, Cox regression, score process plot, Kolmogorov-type supremum test, and linear regression were performed. Results: Results did not show a significant relationship between CRP level on first day of hospitalization, the day of myeloid and platelet engraftment, and duration of hospitalization (P values= 0.91, 0.68, 0.39 respectively). Conclusion: Future studies, assessing changes in CRP levels, along with the impact of other inflammatory factors during conditioning chemotherapy or the day of stem cell injection, might improve our understanding of lymphoma and multiple myeloma treatment and management.

Background: Acute graft-versus-host disease (aGvHD) is a complex and often multisystem disease that causes morbidity and mortality in 35% of patients receiving allogeneic hematopoietic stem cell transplantation (AHSCT). Objective: This study aimed to implement a Clinical Decision Support System (CDSS) for predicting aGvHD following AHSCT on the transplantation day.Material and Methods: In this developmental study, the data of 182 patients with 31 attributes, which referred to Taleghani Hospital Tehran, Iran during 2009–2017, were analyzed by machine learning (ML) algorithms which included XGBClassifier, HistGradientBoostingClassifier, AdaBoostClassifier, and RandomForestClassifier. The criteria measurement used to evaluate these algorithms included accuracy, sensitivity, and specificity. Using the machine learning developed model, a CDSS was implemented. The performance of the CDSS was evaluated by Cohen’s Kappa coefficient. Results: Of the 31 included variables, albumin, uric acid, C-reactive protein, donor age, platelet, lactate Dehydrogenase, and Hemoglobin were identified as the most important predictors. The two algorithms XGBClassifier and HistGradientBoostingClassifier with an average accuracy of 90.70%, sensitivity of 92.5%, and specificity of 89.13% were selected as the most appropriate ML models for predicting aGvHD. The agreement between CDSS prediction and patient outcome was 92%. Conclusion: ML methods can reliably predict the likelihood of aGvHD at the time of transplantation. These methods can help us to limit the number of risk factors to those that have significant effects on the outcome. However, their performance is heavily dependent on selecting the appropriate methods and algorithms. The next generations of CDSS may use more and more machine learning approaches.

B‐cell chronic malignancies, including chronic lymphocytic leukemia and lymphomas, are among the most common blood malignancies. Conventional therapies for these lymphoproliferative diseases include chemotherapy and radiotherapy. However, treating these types of cancer is still challenging due to developing resistance to chemotherapy drugs and even novel agents like immunochemotherapy. Therefore, many studies are underway to clarify the mechanisms involved in this phenomenon. Recently, the role of noncoding RNAs in regulating gene expression has been well documented in the literature. microRNAs are small noncoding RNAs that regulate gene expression at transcriptional and posttranscriptional levels. Long noncoding RNAs are involved in cell differentiation and tissue development via transcriptional and posttranscriptional regulation. Several miRNAs regulate B‐cell development and stimulate activation in normal or malignant B‐cells. Molecular assessments revealed the relationship between the up/downregulation of different genes and the development of therapeutic resistance. Studies suggest that the dysregulation of these molecules could be the missing link in developing resistance to chemotherapy drugs. Serum levels of miRNAs can be employed as a predictive biomarker for diagnosis, prognosis, and response to treatment in B‐cell malignancies. This study reviews the role of different microRNAs and long noncoding RNAs in regulating the expression of genes involved in drug resistance in B‐cell chronic lymphocytic leukemia and lymphomas. [ABSTRACT FROM AUTHOR]

Background: Thrombocytopenia is a frequent complication after hematopoietic stem cell transplantation (HSCT). Although platelet transfusion is the most used treatment for severe thrombocytopenia, it is associated with well-established risks. High-intensity interval exercise (HIIE) results in thrombocytosis. Therefore, this study aimed to reduce thrombocytopenia by increasing platelet count through exercise. Materials and Methods: Twenty lymphoma and multiple myeloma patients were divided into HIIE and control groups. To determine the maximal exercise capacity, patients in the HIIE group performed a graded exercise test. All patients received granulocyte colony-stimulating factor for 5 days, followed by a HIIE trial. After 5 min warm up at 10 to 20% of peak power, patients in the HIIE group performed an HIIE protocol that included 12 intervals of one-minute work at 100% peak power interspersed by one-minute active rest at 20% of peak power. Patients in the control group were seated for the same duration without any physical activity. Two blood samples were taken before and immediately after the trials and were analyzed for measuring complete blood count. Results: Platelet count on the day of platelet engraftment in the HIIE group was significantly higher than in the control group (P=0.02). Single-donor platelet transfusion was significantly lower in the HIIE group than in the control group (P=0.05). Conclusion: Based on the findings of the present study, a short bout of HIIE had a positive effect on platelet engraftment through thrombocytosis and reduced platelet transfusion and its complications, which could be a useful strategy for HSCT patients. [ABSTRACT FROM AUTHOR]

Abstract We aimed to construct a biodegradable transparent scaffold for culturing corneal endothelial cells by incorporating chitosan nanoparticles (CSNPs) into chitosan/polycaprolactone (PCL) membranes. Various ratios of CSNP/PCL were prepared in the presence of constant concentration of chitosan and the films were constructed by solvent casting method. Scaffold properties including transparency, surface wettability, FTIR, and biocompatibility were examined. SEM imaging, H&E staining, and cell count were performed to investigate the HCECs adhesion. The phenotypic maintenance of the cells during culture was investigated by flow cytometry. Transparency and surface wettability improved by increasing the CSNP/PCL ratio. The CSNP/PCL 50/25, which has the lowest WCA, showed comparable transparency with human acellular corneal stroma. The scaffold was not cytotoxic and promoted the HCECs proliferation as evaluated by MTT assay. Cell counting, flow cytometry, SEM, and H&E results showed appropriate attachment of HCECs to the scaffold which formed a compact monolayer. The developed scaffold seems to be suitable for use in corneal endothelial regeneration in terms of transparency and biocompatibility.

Abstract We are going through the greatest global health crisis of the last decades, the coronavirus disease 2019 (COVID‐19) pandemic. It may cause morbidity and mortality in some cases, and there is no therapeutic approach with reproducible and favorable outcomes. As clinical manifestations differ from patient to patient, any report regarding clinical symptoms has been beneficial for early detection and treatment. Due to the immunomodulatory effect of mesenchymal stem cells (MSCs), MSCs‐based therapy has been approved to be one of the therapeutic strategies for COVID‐19 management. For the first time in the literature, we reported generalized lymphadenopathy with fever and no sign of respiratory distress in a 16‐year‐old patient with confirmed COVID‐19 infection as the main clinical signs. We also introduce decidual stromal cells as a potential immunomodulatory treatment for COVID‐19–infected patients.