Search

Hussein A Abbas,* Mansour Alfayez,* Tapan Kadia, Farhad Ravandi-Kashani, Naval Daver Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA*These authors contributed equally to this workCorrespondence: Naval DaverDepartment of Leukemia, University of Texas M. D. Anderson Cancer Center, 1400 Holcombe Boulevard, Unit FC 4.2012, Houston, TX 77030, USATel +1713-794-4392Email NDaver@mdanderson.orgAbstract: Fms-related-tyrosine kinase 3 (FLT3) mutations occur in approximately a third of acute myeloid leukemia (AML) patients and confer an adverse prognosis. Numerous studies have evaluated FLT3 targeting as single agent and in combination approaches in frontline and relapsed AML. At this time, midostaurin, a multikinase inhibitor, is the only FLT3-inhibitor that is US FDA approved to be used in combination with induction therapy in the frontline FLT3-mutated AML setting based on improved overall survival noted in the RATIFY Phase III trial. The utility of midostaurin in maintenance post stem cell transplantation has shown promising results and further studies are still ongoing. In this review, we discuss the studies that led to the inception of midostaurin as a targeted kinase inhibitor, its evaluation in AML, the early clinical trials and the large Phase III clinical trial that led to its eventual US FDA-approval in FLT3-mutated AML. Our review also discusses data on midostaurin adverse effects, mechanisms of resistance and limitations of its utility. We further discuss emerging second-generation FLT3 inhibitors, with a focus on quizartinib and gilteritinib and future directions to enhance FLT3-inhibitor efficacy and overcome mechanisms of resistance.Keywords: acute myeloid leukemia, FLT3, midostaurin

Abstract As the proliferation of video content continues, and many video archives lack suitable metadata, therefore, video retrieval, particularly through example‐based search, has become increasingly crucial. Existing metadata often fails to meet the needs of specific types of searches, especially when videos contain elements from different modalities, such as visual and audio. Consequently, developing video retrieval methods that can handle multi‐modal content is essential. An innovative Multi‐modal Video Search by Examples (MVSE) framework is introduced, employing state‐of‐the‐art techniques in its various components. In designing MVSE, the authors focused on accuracy, efficiency, interactivity, and extensibility, with key components including advanced data processing and a user‐friendly interface aimed at enhancing search effectiveness and user experience. Furthermore, the framework was comprehensively evaluated, assessing individual components, data quality issues, and overall retrieval performance using high‐quality and low‐quality BBC archive videos. The evaluation reveals that: (1) multi‐modal search yields better results than single‐modal search; (2) the quality of video, both visual and audio, has an impact on the query precision. Compared with image query results, audio quality has a greater impact on the query precision (3) a two‐stage search process (i.e. searching by Hamming distance based on hashing, followed by searching by Cosine similarity based on embedding); is effective but increases time overhead; (4) large‐scale video retrieval is not only feasible but also expected to emerge shortly.

Abstract Cystic fibrosis transmembrane conductance regulator (CFTR) protein is an ion channel found in numerous epithelia and controls the flow of water and salt across the epithelium. The aim of our study to find natural compounds that can improve lung function for people with cystic fibrosis (CF) caused by the p.Gly628Arg (rs397508316) mutation of CFTR protein. The sequence of CFTR protein as a target structure was retrieved from UniProt and PDB database. The ligands that included Armepavine, Osthole, Curcumin, Plumbagine, Quercetin, and one Trikafta (R*) reference drug were screened out from PubChem database. Autodock vina software carried out docking, and binding energies between the drug and the target were included using docking-score. The following tools examined binding energy, interaction, stability, toxicity, and visualize protein-ligand complexes. The compounds having binding energies of −6.4, −5.1, −6.6, −5.1, and − 6.5 kcal/mol for Armepavine, Osthole, Curcumin, Plumbagine, Quercetin, and R*-drug, respectively with mutated CFTR (Gly628Arg) structure were chosen as the most promising ligands. The ligands bind to the mutated CFTR protein structure active sites in hydrophobic bonds, hydrogen bonds, and electrostatic interactions. According to ADMET analyses, the ligands Armepavine and Quercetin also displayed good pharmacokinetic and toxicity characteristics. An MD simulation for 200 ns was also established to ensure that Armepavine and Quercetin ligands attached to the target protein favorably and dynamically, and that protein-ligand complex stability was maintained. It is concluded that Armepavine and Quercetin have stronger capacity to inhibit the effect of mutated CFTR protein through improved trafficking and restoration of original function.

Neuroblastoma is an aggressive malignancy commonly found in children, with adult patients being quite rare. Pancreatic neuroblastoma, even among adult cases, is especially rare. We present a case of a 26-year-old woman presented with mild abdominal pain and a palpable mass diagnosed as neuroblastoma affecting the pancreas. After initial diagnostic challenges, a biopsy confirmed the diagnosis of neuroblastoma. The patient thereafter underwent a course of neoadjuvant chemotherapy, followed by a complex surgical resection. This case highlights the importance of a comprehensive diagnostic approach, including repeated biopsies and the involvement of a multidisciplinary team in the management of rare presentations of adult neuroblastoma.

Compost is commonly utilized to improve properties of infertile sandy soils, despite its high biodegradability which may increase greenhouse gases emissions. It is possible to combine compost with biochar, which degrades at a slower rate, forming a “co-composted biochar” product. This mixture could enhance plant growth parameters beyond those attained for using each component, individually. To investigate this assumption, zucchini was selected as a test plant to be grown, under greenhouse conditions, on a sandy soil that received biochar, compost or co-composted biochar (from rice straw or sugarcane bagasse (SB)) for a duration of 15 days. This timeframe was deemed sufficient to achieve a relatively stable degradation rate for compost. Application of organic materials increased both fresh and dry weights of zucchini plants, particularly when co-composted biochar of SB was used. Specifically, plant fresh weights increased by 1.24–1.71 folds when using this additive versus the control group. Additionally, availability of nitrogen, phosphorus, and potassium in soil and their uptake by plants significantly increased owing to application of all additives, with superiority for the co-composted biochar of SB. Enhancements in plant fresh weights were strongly correlated with increasing availability and uptake of phosphorus by plants. In conclusion, organic amendments have a substantial positive impact on enhancing the nutritional status and growth of zucchini, even during the early vegetative growth stage (within the first 15 days after planting). The greatest improvements were observed when co-composted biochar of SB was used and this confirm the main hypothesis of the study.

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.

The present study investigates the perceptions and practices of a group of university students and instructors at an English Medium university in Northern Cyprus. The study examines the relationship between attitudes and perceptions towards English Medium Instruction (EMI) and English as an Academic lingua franca (ELFA). The research adopts a mixed-methods approach, incorporating a survey distributed among 200 students and interviews conducted with 4 students and 6 instructors. The survey results are analyzed with SPSS 23 to provide descriptive statistical analysis, correlation, and regression analysis. The interview data undergoes thematic analysis to uncover patterns and provide qualitative insights. The study indicates differing perceptions and attitudes between students and instructors. Instructors tend to perceive students’ attitudes towards EMI/ELFA as negative, while students themselves exhibit positive attitudes toward these instructional methods. Additionally, the study sheds light on the significant challenges faced by both students and instructors, including issues related to low language proficiency, self-confidence, and comprehension problems within the EMI context. The research also highlights the diverse strategies employed by students to overcome these challenges. The findings have potential implications for other similar EMI contexts.

The use of electromagnetic fields (EMFs) is essential in daily life. Since 1970, concerns have grown about potential health hazards from EMF. Exposure to EMF can stimulate nerves and affect the central nervous system, leading to neurological and cognitive changes. However, current research results are often vague and contradictory. These effects include changes in memory and learning through changes in neuronal plasticity in the hippocampus, synapses and hippocampal neuritis, and changes in metabolism and neurotransmitter levels. Prenatal exposure to EMFs has negative effects on memory and learning, as well as changes in hippocampal neuron density and histomorphology of hippocampus. EMF exposure also affects the structure and function of glial cells, affecting gate dynamics, ion conduction, membrane concentration, and protein expression. EMF exposure affects gene expression and may change epigenetic regulation through effects on DNA methylation, histone modification, and microRNA biogenesis, and potentially leading to biological changes. Therefore, exposure to EMFs possibly leads to changes in cellular and molecular mechanisms in central nervous system and alter cognitive function.

Cannabidiol (CBD) is a non-psychoactive drug extracted from marijuana. It is well established that CBD attenuates the reinforcing effects of drugs of abuse, although its mechanism of action is not fully understood. The current study tries to clarify the role of D1-like dopamine receptors (D1R) in the ventral tegmental area (VTA) in the inhibitory effects of the CBD on the acquisition and expression of methamphetamine (METH)-conditioned place preference (CPP). In the CPP training, adult male Wistar rats were conditioned with subcutaneous administration of METH (1 mg/kg) for five days. Three groups of animals were treated with multiple doses of SCH23390 (as a D1R antagonist; 0.25, 1, and 4 μg/0.3 μl saline) in the VTA, respectively, before intracerebroventricular (ICV) injection of CBD (10 μg/5 μl DMSO) in the acquisition phase. In the second experiment of the study, rats received SCH23390 in the VTA before ICV administration of CBD (50 μg/5 μl DMSO) in the expression of METH CPP. Here, the current study demonstrated that CBD inhibits the acquisition and expression of METH CPP, while microinjection of D1R antagonists (1 and 4 μg) into the VTA significantly reduced CBD’s suppressive effect on the acquisition and expression of METH place preference. Furthermore, this research demonstrated that either SCH23390 or CBD alone does not lead to place preference in the CPP paradigm. Based on these data, this study suggests that pharmacological manipulations of D1R may alter the CBD’s effect on METH-conditioned preference.

Abstract A new technique is proposed for loss of field (LOF) detection in synchronous generators (SGs). The proposed scheme employs the variations of SG angular velocity ∆ωφ and load angle ∆δφ to reach this goal, while the mentioned parameters are estimated through air gap flux estimation. The proposed scheme performance is evaluated using realistic simulation case studies based on IEEE C. 37. 102 standard compared to the conventional impedance‐based one. The obtained results show that the presented scheme excels the conventional scheme from speed and security viewpoints. Moreover, the estimation procedure of ∆ωφ and ∆δφ is experimentally validated by using a 10 kVA SG and the results demonstrate that the proposed technique can be easily set and implemented.

Abstract Expanding floating wind into new markets could support emission reduction targets in several national contexts. It furthers the need for adequate assessments to gain a full understanding of the technology’s potential in future markets. South Africa is a prime case study as it has seen limited industry and policy developments despite its huge technical potential for floating offshore wind (FOW). This paper assessed the locational potential of floating wind in South Africa through a three-phased approach that evaluated the key technical drivers/barriers of the technology, conducted a Geographic Information System analysis (GIS) using ArcMap 10.8 to exclude unsuitable sites based on a predetermined exclusion criteria (including marine protected zones, underwater cables, major oil and gas deposits, etc.), and estimated the total harvestable capacity in the feasible sites. The study found that 2% (246,105.4 km2) of South Africa’s entire Exclusive Economic Zone (EEZ) is suitable for hosting floating wind turbines, with a potential to generate a maximum of 142.61 GW of floating wind power. Although the Western Cape province holds the highest potential (80.52 GW) for floating wind in the country, the Eastern Cape region, with a locational potential of 20.04 GW, is considered most suitable for early-stage developments due to the availability of grid connection points, limited marine traffic, and proximity to appropriate port facilities. Future work can conduct techno-economic assessments to evaluate the technical and economic implications of developing floating wind in distinct sites in the country’s EEZ.

The efficiency of the foreign exchange market is crucial because exchange rates play a vital role in balancing a nation's internal and external economies. Iran's foreign exchange market has undergone significant developments and fluctuations in recent years, impacting its efficiency. This is evident in the monthly time series data for the unofficial exchange rates of the dollar, euro, and yuan from 2001 to 2021. An interesting trend has emerged since 2017: the Chinese yuan appears to be gradually replacing the dollar and euro as the primary trading currency in Iran's international market. Statistical tests, including the Augmented Dickey-Fuller (ADF), Phillips-Peron (PP), and KPSS tests, indicate weak-form efficiency in the markets for all three currencies (dollar, euro, and yuan). This suggests that these markets remain vulnerable to speculative attacks. Furthermore, Johansen's cointegration and Granger's causality tests reveal an absence of semi-strong efficiency in all three markets. This implies that past price information alone is insufficient to predict future exchange rates. The research findings suggest that choosing the yuan as an alternative currency has had a somewhat positive impact on improving the efficiency of the Iranian currency market.

Abstract The study focused on the morphological and chemical characteristics of 200 Hymenocrater longiflorus Benth. genotypes found in natural habitats of eight regions in west of Iran. The primary objective of the study was to assess the morphological and phytochemical variability within populations grown in their natural habitats, with the aim of identifying their potential for domestication and utilization in pre-breeding programs. The plant height (PH) ranged from 50.32 to 69.65 cm, with the highest observed in population P8. The internode distances ranged from 4.7 to 6.47 cm, with the maximum distance found in P4. Flower lengths varied from 1.95 to 2.45 cm, with the minimum and maximum values observed in P4 and P3, respectively. The highest leaf length (5.20 cm) and width (3.87 cm) were recorded in P2. The aerial parts of the plant were utilized to extraction and determine the essential oil (EO) content and composition, which ranged from 0.40 to 0.78% (v/w). The analysis of EO by gas chromatography (GC) and gas chromatography mass spectrometry (GC/MS) identified 26 compounds, constituting 99–99.5% of the EOs. The main compounds in the EO and their percentage range (v/w DW) were tau-cadinol (0.62–55.56), mono (2-ethylhexyl) phthalate (8.10–94.70), elemol (0.21–19.11), β-spathulenol (0.08–14.39), 4-terpineol (0.23–10.19), and β-eudesmol (0.21–9.94). The main chemical groups found in EOs included oxygenated sesquiterpenes (1.12–68.43), and phthalates (9.73–94.72). Cluster analysis revealed three distinct chemotypes: chemotype I (populations 1 and 2) with major components of mono (2-ethylhexyl) phthalate, tau-cadinol, and α-elemol; chemotype II (population 5) rich in mono (2-ethylhexyl) phthalate; and chemotype III (populations 3, 4, 6–8) containing tau-cadinol, β-eudesmol, and 4-terpineol. The study also evaluated total phenolic, total flavonoid, and DPPH free radical scavenging activity in the fifty percent inhibitory concentration (IC50) in leaf and flower samples of the genotypes, along with estimating total anthocyanin content in the flower samples. The total phenolic content (TPC) in leaf and flower samples ranged from 7.89 to 107.18 mg GAE/g DW and 39.98 to 86.62 mg gallic acid equivalent (GAE)/g DW, respectively. Total flavonoid content (TFC) ranged from 81.04 to 143.46 mg QUE/g DW in leaf samples and from 94.82 to 133.26 mg quercetin equivalent (QUE)/g DW in flower samples. DPPHsc IC50 (µg/mL) ranged from 0.65 to 78.74 in leaf samples and from 4.38 to 7.71 in flower samples. Anthocyanin content ranged from 1.89 to 3.75 mg cyanidin-3-glucoside equivalent (C3GE)/g DW among populations. Canonical correspondence analysis and simple correlation demonstrated a strong association and correlations among the studied attributes. The negative correlations between leaf DPPH (DPPH L) IC50 and TFC (− 0.73), TPC (− 0.63), Elemol (− 0.90), and EO (− 0.85) indicate that these compounds have a significant impact on the antioxidant activity of the leaves. Furthermore, Fruit DPPH (DPPH F) IC50 showed a negative correlation with TPC (− 0.79) and TFC (− 0.78), but a positive correlation with flower anthocyanins (0.51), (Z)-β-Farnesene (0.66), and 4-Terpineol (0.57). Circular cluster analysis categorized the genotypes of all individuals in the eight studied populations into three main categories based on all the studied traits, indicating significant variation in phytochemical and morphological traits among populations, surpassing the within-populations variation.

Abstract Background This animal study sought to evaluate two novel nanomaterials for pulpotomy of primary teeth and assess the short-term pulpal response and hard tissue formation in dogs. The results were compared with mineral trioxide aggregate (MTA). Methods This in vivo animal study on dogs evaluated 48 primary premolar teeth of 4 mongrel female dogs the age of 6–8 weeks, randomly divided into four groups (n = 12). The teeth underwent complete pulpotomy under general anesthesia. The pulp tissue was capped with MCM-48, MCM-48/Hydroxyapatite (HA), MTA (positive control), and gutta-percha (negative control), and the teeth were restored with intermediate restorative material (IRM) paste and amalgam. After 4–6 weeks, the teeth were extracted and histologically analyzed to assess the pulpal response to the pulpotomy agent. Results The data were analyzed using the Kruskal‒Wallis, Fisher’s exact, Spearman’s, and Mann‒Whitney tests. The four groups were not significantly different regarding the severity of inflammation (P = 0.53), extent of inflammation (P = 0.72), necrosis (P = 0.361), severity of edema (P = 0.52), extent of edema (P = 0.06), or connective tissue formation (P = 0.064). A significant correlation was noted between the severity and extent of inflammation (r = 0.954, P

Abstract Background After the outbreak of COVID-19, a huge part of the health care services was dedicated to preventing and treating this disease. In case of COVID-19 infection, severe COVID-19 is reported more in pregnant individuals. Afterward, Vaccination against SARS-CoV-2 became a hot topic due to known effects in preventing severe COVID-19 during pregnancy. Vaccination of pregnant individuals started in August 2021 with the Sinopharm vaccine in Iran. The aim of current study was to determine the incidence of perinatal outcomes in women who were vaccinated during pregnancy. Method This retrospective cohort study included 129,488 singleton births from March 21, 2021, until March 21, 2022, in Tehran, Iran. The data was obtained from the Iranian Maternal and Neonatal (IMaN) Network and the Maternal Vaccination Registry. Adverse perinatal outcomes investigated in this study include preterm birth, extremely preterm birth, low birth weight, very low birth weight, intrauterine growth restriction, stillbirth, neonatal intensive care unit admission, congenital anomaly, neonatal death and low 5-minute Apgar score. The risk of all perinatal outcomes was evaluated using multiple logistic regression. The analysis was done using STATA version 14. Results Of all 129,488 singleton births included in this study, 17,485 (13.5%) were vaccinated against SARS-CoV-2 (all with Sinopharm (BBIBP-CorV)). The exposure to the Sinopharm vaccine during pregnancy caused a significant decrease in the incidence of preterm birth (P =0.006, OR=0.91 [95% CI, 0.85 to 0.97]), extremely preterm birth (P =

Abstract Background Ventilator-associated pneumonia (VAP) is one of the leading causes of mortality in patients with critical care illness. Since obesity is highly prevalent, we wanted to study its impact on the outcomes of patients who develop VAP. Methods Using the National Inpatient Sample (NIS) database from 2017 to 2020, we conducted a retrospective study of adult patients with a principal diagnosis of VAP with a secondary diagnosis with or without obesity according to 10th revision of the International Statistical Classification of Diseases (ICD-10) codes. Several demographics, including age, race, and gender, were analyzed. The primary endpoint was mortality, while the secondary endpoints included tracheostomy, length of stay in days, and patient charge in dollars. Multivariate logistic regression model analysis was used to adjust for confounders, with a p-value less than 0.05 considered statistically significant. Results The study included 3832 patients with VAP, 395 of whom had obesity. The mean age in both groups was around 58 years, and 68% of the group with obesity were females compared to 40% in females in the group without obesity. Statistically significant comorbidities in the obesity group included a Charlson Comorbidity Index score of three and above, diabetes mellitus, hypertension, chronic kidney disease, and sleep apnea. Rates and odds of mortality were not significantly higher in the collective obesity group 39 (10%) vs. 336 (8.5%), p-value 0.62, adjusted odds ratio 1.2, p-value 0.61). The rates and odds of tracheostomy were higher in the obesity group but not statistically significant. Obese patients were also found to have a longer hospitalization. Upon subanalysis of the data, no evidence of racial disparities was found in the care of VAP for both the obese and control groups. Conclusions Obesity was not found to be an independent risk factor for worse outcomes in patients who develop VAP in the intensive care unit.

Prescribing drugs in a traditional way causes drug resistance and side effects. New strategies are being developed to solve these problems and to deliver drugs safely and efficiently to damaged tissues. Drug delivery systems are one of the successful strategies for delivering drugs to the disease site in the body. Hydroxyapatite (HA) due to its similarity to the compositional of bone and tooth and biocompatibility has received more attention in biomedical applications. Nonetheless, its applications are restricted by lower mechanical potency, low colloidal stability, and uncontrolled drug release. The composition of HA with polymers removes its defects as a drug delivery system. Hence, this paper provides clear information on the latest Hydroxyapatite nanocomposites (HAP-PNs) improvements as drug delivery systems. So, it supplies a precise insight into the various synthesis methods of HAp-PNs and newly developed nanocarriers from HAp-PNs. Moreover, this review confers HAp-PNs nanocarrier's possible usage and restrictions in different fields of medicine.

Background: One of the targeted drug delivery systems is the use of nanocarriers, and one of these drug delivery systems is niosome. Niosome have a nano-vesicular structure and are composed of non-ionic surfactants. Objective: In this study, various niosome-encapsulated meropenem formulations were prepared. Subsequently, their antibacterial and anti-biofilm activities were evaluated against methicillin-resistant Staphylococcus aureus (MRSA) strains. Methods: The physicochemical properties of niosomal formulations were characterized using a field scanning electron microscope, X-Ray diffraction, Zeta potential, and dynamic light scattering. Antibacterial and anti-biofilm activities were evaluated using broth microdilution and minimum biofilm inhibitory concentration, respectively. In addition, biofilm gene expression analysis was performed using quantitative Real-Time PCR. To evaluate biocompatibility, the cytotoxicity of niosome-encapsulated meropenem in a normal human diploid fibroblast (HDF) cell line was investigated using an MTT assay. Results: An F1 formulation of niosome-encapsulated meropenem with a size of 51.3 ± 5.84 nm and an encapsulation efficiency of 84.86 ± 3.14 % was achieved. The synthesized niosomes prevented biofilm capacity with a biofilm growth inhibition index of 69 % and significantly downregulated icaD, FnbA, Ebps, and Bap gene expression in MRSA strains (p 90 % at all tested concentrations against normal HDF cells. The results of the present study indicate that niosome-encapsulated meropenem increased antibacterial and anti-biofilm activities without profound cytotoxicity in normal human cells, which could prove useful as a good drug delivery system.

The combination polymers or copolymers have new and combined properties and increase the efficiency of the new polymer. Biopolymers are biodegradable and can play the role of biocompatible and biodegradable in composite polymers. Therefore, poly ortho–toluidine was grafted on chitosan (Cs-g-POT) by chemical and electrochemical polymerization methods. Cs-g-POT was characterized by FTIR, UV–visible, and 1H NMR spectroscopy techniques. The thermal behaviors of the copolymer were investigated by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The images of the surface of the copolymer obtained from imaging SEM confirm the successful attachment of POT on chitosan and indicate that the graft polymerization has been successfully performed with both methods. The percentage and efficiency of engraftment were carefully measured and reported. The electrical conductivity of Cs-g-POT was measured by the four-point method and the conductivity was 9.1 × 10−4 S/cm. The copolymer's antibacterial property was studied on Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa as a common bacterium in skin wounds. These studies were investigated using the disk diffusion and minimum inhibitory concentration (MIC) methods. In all tested concentrations the polymer could inhibit the growth of E. coli and P. aeruginosa significantly. However, it inhibited the growth of S. aureus in concentrations above 1 μg. Bacteria are adsorbed on the surface of the polymer by polar-polar and Van Der Waals interactions, where they undergo cell lysis by dopant and electron transfer, and eventually bacterial cell death. Due to its scaffolding properties, this polymer will have a very good use in tissue and bone repair as well as anti-cancer drugs.

Previous studies have established that the amygdala specifically the basolateral amygdala (BLA), has a fundamental role in decision-making. The present study aimed to investigate functional and neural synchronization between the BLA and anterior cingulate cortex (ACC) while making effort-choice decisions regarding pre-morphine dependence and morphine dependence times. A T-maze decision-making task with a differential outlay (great vs. small effort) and benefit (great vs. small reward) was done, and local field potentials from the BLA and ACC were assessed simultaneously. Results illustrated that in pre-morphine dependence time, when the animals made great reward/great effort decisions, there was a neural synchronization between both regions in beta and gamma frequency bands; and also, in delta, theta, beta, and gamma frequencies while expending effort and climbing the barrier. However, in morphine-dependent rats, during low reward/low effort choice and also during expending low effort, there was just a weak neural coherence in gamma frequency. Besides, there was neural synchronization in theta, beta, and gamma frequencies during reaching great reward in pre-morphine dependence time. Nevertheless, during reaching low reward in morphine dependence time, there was a weaker coherence in beta and gamma compared to pre-morphine dependence. These findings showed that functional and neural coherence between the BLA and ACC has a fundamental role in making the effort-based decision and expending effort. Preference for low reward/low effort, and decrease in expending effort in morphine-dependent rats is partly associated with the changes in the neural coherence between the BLA and ACC.

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 The orexin/hypocretin receptor type 1 (OX1R) plays a crucial role in regulating various physiological functions, especially feeding behavior, addiction, and reward. Genetic variations in the OX1R have been associated with several neurological disorders. In this study, we utilized a combination of sequence and structure-based computational tools to identify the most deleterious missense single nucleotide polymorphisms (SNPs) in the OX1R gene. Our findings revealed four highly conserved and structurally destabilizing missense SNPs, namely R144C, I148N, S172W, and A297D, located in the GTP-binding domain. Molecular dynamics simulations analysis demonstrated that all four most detrimental mutant proteins altered the overall structural flexibility and dynamics of OX1R protein, resulting in significant changes in the structural organization and motion of the protein. These findings provide valuable insights into the impact of missense SNPs on OX1R function loss and their potential contribution to the development of neurological disorders, thereby guiding future research in this field.

Background: Ferula assa-foetida is an herbaceous plant from Apiaceae family. Several pharmacological effects of oleo-gum resin of this plant were introduced in modern and traditional medicines such as digestive, antimicrobial, anti-diabetic, appetizing, insecticidal, and etc. Objectives: This study aimed to acute and sub-chronic toxicity of chloroform fraction of oleo-gum extract of Ferula in Wistar rats. The safety of this can guarantee its use in treatment and various industries. Methods: Rats in six groups including male and female (kept separately) at different doses (50 mg/kg, 500 mg/kg, and 2000 mg/kg) and two control groups (control and DMSO( were selected to evaluate the acute toxicity of chloroform fraction of Ferula. For 30 days, 50 mg/kg and 250 mg/kg of sample was administrated to male and female rats. Mortality, appearance and behavioral changes, food intake, the weight of rats, and hematological, biochemical variables and histopathological changes were examined. Results: Physical and behavioral changes were not observed in acute and sub-chronic toxicity conditions. Food intake significantly differed between male and female DMSO control and other groups. In biochemical variables study, only SGOT (AST) showed a significant difference from the control group (DMSO) in acute toxicity and BUN, ALP and SGOT (AST) in sub-chronic toxicity. Also, any histopathological change was observed in spleen, liver, and kidney organs. Conclusion: Oleo-gum resin of F. assa-foetida has not toxic effects, so it should be used with caution in the long term.

Background: Fenugreek is one of the most widely used medicinal plants in terms of therapeutic properties, and numerous pharmacological effects have been found in various studies. Fenugreek seed extract contains many effective substances, including phytosterols (mainly β-Sitosterol). Objective: This investigation was conducted to determine the optimal extraction method for fenugreek seeds based on the amount of β-Sitosterol detected on HPLC using a response surface methodology (RSM). Methods: At first, the appropriate solvent was selected. The main variables affecting the extraction efficiency, including temperature, time, solvent percentage, and the ratio of solvent to powder, were investigated to optimize the best method. Optimizing the number of 29 experiments determined that extraction was done using the dynamic maceration method. After finding the optimized method, the extracts were injected into the HPLC device three times to determine the amount of total β-Sitosterol. Then it was modelled, and the final formula was obtained. Results: The analysis of results were shown that the optimal extract (based on the amount of total β-Sitosterol and weight), using the dynamic maceration extraction method with 96 % ethanol at a temperature of 44 ˚C, a duration of 30 minutes, a solvent percentage of 70 % and a ratio of solvent to powder of 7:1 was obtained. Conclusion: The findings suggest the, this method seams the most efficient for maximum extraction of the β-Sitosterol compound from fenugreek seeds.

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.

Understanding the molecular mechanisms of differentiation is important for regenerative medicine and developmental biology. This study aims to characterise the role of the glycolysis/oxidative phosphorylation balance as a driver of mesenchymal stem cell (MSC) differentiation. Cells were maintained in normal conditions or stimulated towards the MSC trilineage cell types over 21 days. Multispectral imaging of cell autofluorescence was applied as a non-invasive methodology to continuously image cultures in situ. Spectral signals for collagen, NAD(P)H, and flavins were unmixed. MSCs cultured under chondrogenic conditions exhibited increased collagen levels relative to controls. Following osteogenic induction, MSCs showed increased collagen levels relative to controls during the earlier stages of culture; however, control cells increased their collagen levels as they became confluent. MSCs cultured under adipogenic conditions exhibited lower levels of collagen than controls. The redox ratio (RR; NAD(P)H/flavins) immediately decreased during chondrogenesis, with this early effect persisting throughout the culture compared to control cells, which appeared to increase their RR, similar to osteogenesis. Adipogenesis resulted in a small increase in RR on day 2 relative to control cells, followed by a persistent decrease. Chondrogenic and adipogenic differentiation favoured oxidative phosphorylation, whereas osteogenesis and MSC overgrowth resulted in a glycolytic metabolism. Following consideration of these findings, as well as the diverse reports in the literature, it is concluded that neither enhanced oxidative phosphorylation nor glycolysis are fundamental to the canonical modes of differentiation, and researchers should avoid interpreting shifts as indicating differentiation.

Introduction: Inferior alveolar nerve (IAN) exposure and neurosensory disturbances (NSDs) following bilateral sagittal split osteotomy (BSSO) of the mandible are paramount. We aimed to assess intraoperative IAN exposure during and NSDs after BSOO surgery using different clinical assessment methods in a prospective study in a local setting. Materials and Methods: The present study was a prospective cross-sectional study. We monitored the nerve exposure status during the BSSO. Our time points were: before surgery, one day after, one month later, three months after and six months after the BSSO surgery. We performed two-point discrimination test, static light touch test and pinprick test on both mental regions of the cases. Results: We included seven women and eight men. The average age of the participants was 25.13±3.27 years. The results of the two-point discrimination test showed the following: the day after the BSSO compared to before the surgery, the sensation is significantly impaired in both mental regions. In addition, it is noted that during our study, the two-point discrimination test results showed a gradient healing, though not reaching the point before the surgery (P>0.05). The results of the Pinprick test also showed a gradual resolution of the NSDs; however, a significant sensation difference remained between six months after the BSSO and before the surgery. Conclusion: The BSSO surgery significantly impairs the IAN sensation, causing intraoperative IAN exposure and postoperative NSDs for the patients. A gradient resolution of the NSDs was observed in all the cases, though; the sensation of the mental region did not reach the pre-surgical levels. Keywords: Alveolar nerve; Nerve exposure; Neurosensory disturbance; Sagittal split osteotomy surgery.

Abstract Networks are essential for analyzing complex systems. However, their growing size necessitates backbone extraction techniques aimed at reducing their size while retaining critical features. In practice, selecting, implementing, and evaluating the most suitable backbone extraction method may be challenging. This paper introduces netbone, a Python package designed for assessing the performance of backbone extraction techniques in weighted networks. Its comparison framework is the standout feature of netbone. Indeed, the tool incorporates state-of-the-art backbone extraction techniques. Furthermore, it provides a comprehensive suite of evaluation metrics allowing users to evaluate different backbones techniques. We illustrate the flexibility and effectiveness of netbone through the US air transportation network analysis. We compare the performance of different backbone extraction techniques using the evaluation metrics. We also show how users can integrate a new backbone extraction method into the comparison framework. netbone is publicly available as an open-source tool, ensuring its accessibility to researchers and practitioners. Promoting standardized evaluation practices contributes to the advancement of backbone extraction techniques and fosters reproducibility and comparability in research efforts. We anticipate that netbone will serve as a valuable resource for researchers and practitioners enabling them to make informed decisions when selecting backbone extraction techniques to gain insights into the structural and functional properties of complex systems.

Asceticism has been one of the most important concepts in Arthur Schopenhauer’s philosophy, especially in his theory of salvation. He has defined salvation as releasing from pain and suffering and achieving long-term tranquility. According to him, such tranquility may be achieved by the way of asceticism. Life is suffering according to him. Hence, a way of relief must be sought. Thus, he has thought that the source of all suffering is will. He has actually considered suffering as a phenomenon of will and an essential part of human life. Therefore, will has to be denied, surpassed, and dumbed if relief and peace are required. Denying and ignoring the appetites and wishes makes the relief possible. Thus, he paid special attention to the concept of Asceticism and declared it as the only way of true salvation. This essay tried to explain the concepts of Asceticism and salvation and then show how Asceticism may soothe human beings' sufferings and lead to salvation according to Schopenhauer.

In several applications, the accuracy and robust performance of the control method for the speed of permanent magnet synchronous motors (PMSMs) is critical. Model uncertainties, caused by inaccurate model identification, decrease the accuracy of PMSM control. To solve this problem, this paper presents a super robust control structure for the speed control of PMSMs. In the proposed method, the model uncertainties with Lipschitz condition together with disturbances are considered during the PMSM modeling, and their effects are handled using a robust state feedback control. To be more specific, the Lyapunov stability proof is performed in such a way that the model uncertainty effects are eliminated. Before that, the Lyapunov stability criteria have been selected in such a way that the Hꝏ conditions are considered and guaranteed. This issue helps to eliminate the effects of the disturbances. In addition, this paper considers another option to make the whole control structure robust against sudden load changes. To solve this problem, a fuzzy adaptive sliding mode observer (FASMO) is presented to determine the load torque and use it in the control signal generation. In this observer, the switched gain of the sliding mode observer (SMO) is adapted using a fuzzy system to eliminate the chattering phenomena and increase the estimation accuracy. In fact, the proposed method is called super robust because it resists model uncertainties, disturbances, and sudden load changes during three stages by robust state feedback control, Hꝏ criterion, and load estimator, respectively. The performance of the proposed approach is validated through a set of laboratory tests, and its superiority is shown compared to other methods.

Background and purpose: Appendicitis is one of the reasons for abdominal pain and the most common cause of referral to pediatric emergency departments. There are different results on the frequency and complications of appendicitis during COVID-19 pandemic. This study aims to compare the frequency and complications of acute appendicitis in children who underwent laparotomy before and during the COVID-19 pandemic in Babol Children's Hospital, north of Iran. Materials and methods: This retrospective study was conducted in 172 children with acute appendicitis who underwent laparotomy. Children were divided into two groups according to the time of referral; before the COVID-19 pandemic (between December 2018 and November 2019) and during the pandemic (between March 2019 and February 2020). Surgeon’s observations in laparotomy and also the complications (perforation, abscess, gangrene, and peritonitis) were recorded. Data analysis was carried out using Chi-score and paired t-test. Results: The children studied included 94 before the COVID-19 pandemic and 78 during the pandemic. The average age was 7.76±2.89 years. Findings showed that 165 (95.9%) and 7 (4.1%) children had confirmed and unconfirmed appendicitis, respectively, indicating no significant difference between the two groups (P=0.45). The complications of appendicitis (perforation, gangrene, abscess, and peritonitis) were 8.25% before the pandemic and 34.2% during the pandemic (P=0.24). There was no significant difference between the two groups in average time interval between the onset of pain and attending the hospital (P=0.38). Conclusion: In this study, the COVID-19 pandemic did not affect the frequency of acute appendicitis in children. These results probably indicate the proper performance of the treatment staff and the parents' rapid response to their child’s acute abdominal symptoms during the pandemic.

Abstract Background Oregano (Origanum vulgare L.), one of the important medicinal plants in the world, has valuable pharmacological compounds with antimicrobial, antiviral, antioxidant, anti-inflammatory, antispasmodic, antiurolithic, antiproliferative and neuroprotective activities. Phenolic monoterpenes such as thymol and carvacrol with many medical importance are found in Oregano essential oil. The biosynthesis of these compounds is carried out through the methyl erythritol-4 phosphate (MEP) pathway. Environmental stresses such as salinity might improve the secondary metabolites in medicinal plants. The influence of salinity stress (0 (control), 25, 50 and 100 mM NaCl) on the essential oil content, composition and expression of 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR), γ-terpinene synthase (Ovtps2) and cytochrome P450 monooxygenases (CYP71D180) genes involved in thymol and carvacrol biosynthesis, was investigated in two oregano subspecies (vulgare and gracile). Results Essential oil content was increased at low NaCl concentration (25 mM) compared with non-stress conditions, whereas it was decreased as salinity stress intensified (50 and 100 mM). Essential oil content was significantly higher in subsp. gracile than subsp. vulgare. The highest (0.20 mL pot−1) and lowest (0.06 mL pot−1) amount of essential oil yield was obtained in subsp. gracile at 25 and 100 mM NaCl, respectively. The content of carvacrol, as the main component of essential oil, decreased with increasing salinity level in subsp. gracile, but increased in subsp. vulgare. The highest expression of DXR, Ovtps2 and CYP71D180 genes was observed at 50 mM NaCl in subsp. vulgare. While, in subsp. gracile, the expression of the mentioned genes decreased with increasing salinity levels. A positive correlation was obtained between the expression of DXR, Ovtps2 and CYP71D180 genes with carvacrol content in both subspecies. On the other hand, a negative correlation was found between the expression of CYP71D180 and carvacrol content in subsp. gracile. Conclusions The findings of this study demonstrated that both oregano subspecies can tolerate NaCl salinity up to 50 mM without significant reduction in essential oil yield. Also, moderate salinity stress (50 mM NaCl) in subsp. vulgare might increase the carvacrol content partly via increment the expression levels of DXR, Ovtps2 and CYP71D180 genes.

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.

Abstract Over-expression of K+ channels has been reported in human cancers and is associated with the poor prognosis of several malignancies. EAG1, a particular potassium ion channel, is widely expressed in the brain but poorly expressed in other normal tissues. Kunitz proteins are dominant in metazoan including the dog tapeworm, Echinococcus granulosus. Using computational analyses on one A-type potassium channel, EAG1, and in vitro cellular methods, including major cancer cell biomarkers expression, immunocytochemistry and whole-cell patch clamp, we demonstrated the anti-tumor activity of three synthetic small peptides derived from E. granulosus Kunitz4 protease inhibitors. Experiments showed induced significant apoptosis and inhibition of proliferation in both cancer cell lines via disruption in cell-cycle transition from the G0/G1 to S phase. Western blotting showed that the levels of cell cycle-related proteins including P27 and P53 were altered upon kunitz4-a and kunitz4-c treatment. Patch clamp analysis demonstrated a significant increase in spontaneous firing frequency in Purkinje neurons, and exposure to kunitz4-c was associated with an increase in the number of rebound action potentials after hyperpolarized current. This noteworthy component in nature could act as an ion channel blocker and is a potential candidate for cancer chemotherapy based on potassium channel blockage.

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.

Background The neonatal mortality rate is a main indicator of the health and development of a country. Having insight into the cause of neonatal deaths may be the first step to reducing it. This paper depicts the cause of newborn deaths in Iran.Methods This cross-sectional study was performed on data from the national Iranian Maternal And Neonatal network to investigate all neonatal deaths in the country during the year 2019. The cause of death data were reported according to categories of birth weight, gestational age (GA), death time and place.Results The main causes of the 9959 neonatal deaths during the study period were respiratory distress syndrome (RDS) (37%), malformation (21%), prematurity of

Abstract Depression is a highly prevalent and disabling mental disorder, involving numerous genetic changes that are associated with abnormal functions in multiple regions of the brain. However, there is little transcriptomic‐wide characterization of chronic social defeat stress (CSDS) to comprehensively compare the transcriptional changes in multiple brain regions. Spatial transcriptomics (ST) was used to reveal the spatial difference of gene expression in the control, resilient (RES) and susceptible (SUS) mouse brains, and annotated eight anatomical brain regions and six cell types. The gene expression profiles uncovered that CSDS leads to gene synchrony changes in different brain regions. Then it was identified that inhibitory neurons and synaptic functions in multiple regions were primarily affected by CSDS. The brain regions Hippocampus (HIP), Isocortex, and Amygdala (AMY) present more pronounced transcriptional changes in genes associated with depressive psychiatric disorders than other regions. Signalling communication between these three brain regions may play a critical role in susceptibility to CSDS. Taken together, this study provides important new insights into CSDS susceptibility at the ST level, which offers a new approach for understanding and treating depression.

Nano-based drug delivery systems are increasingly used for diagnosis, prevention and treatment of several diseases, thanks to several beneficial properties, including the ability to target specific cells or organs, allowing to reduce treatment costs and side effects frequently associated with chemotherapeutic medications, thereby improving treatment compliance of patients. In the field of communicable diseases, especially those caused by intracellular bacteria, the delivery of antibiotics targeting specific cells is of critical importance to maximize their treatment efficacy. Brucella melitensis, an intracellular obligate bacterium surviving and replicating inside macrophages is hard to be eradicated, mainly because of the low ability of antibiotics to enter these phagocityc cells . Although different antibiotics regimens including gentamicin, doxycycline and rifampicin are in fact used against the Brucellosis, no efficient treatment has been attained yet, due to the intracellular life of the respective pathogen. Nano-medicines responding to environmental stimuli allow to maximize drug delivery targeting macropages, thereby boosting treatment efficacy. Several drug delivery nano-technologies, including solid lipid nanoparticles, liposomes, chitosan, niosomes, and their combinations with chitosan sodium alginate can be employed in combination of antibiotics to successfully eradicate Brucellosis infection from patients.

Acute myeloid leukemia (AML) is a heterogeneous disease developed from the malignant expansion of myeloid precursor cells in the bone marrow and peripheral blood. The implementation of intensive chemotherapy and hematopoietic stem cell transplantation (HSCT) has improved outcomes associated with AML, but relapse, along with suboptimal outcomes, is still a common scenario. In the past few years, exploring new therapeutic strategies to optimize treatment outcomes has occurred rapidly. In this regard, natural killer (NK) cell-based immunotherapy has attracted clinical interest due to its critical role in immunosurveillance and their capabilities to target AML blasts. NK cells are cytotoxic innate lymphoid cells that mediate anti-viral and anti-tumor responses by producing pro-inflammatory cytokines and directly inducing cytotoxicity. Although NK cells are well known as short-lived innate immune cells with non-specific responses that have limited their clinical applications, the discovery of cytokine-induced memory-like (CIML) NK cells could overcome these challenges. NK cells pre-activated with the cytokine combination IL-12/15/18 achieved a long-term life span with adaptive immunity characteristics, termed CIML-NK cells. Previous studies documented that using CIML-NK cells in cancer treatment is safe and results in promising outcomes. This review highlights the current application, challenges, and opportunities of CIML-NK cell-based therapy in AML.

Background: Abdominal distension in children can be caused by fluid accumulation due to ascites or large cysts. Case Presentation: A 25-month-old girl was brought to the pediatric gastroenterology clinic with the chief complaint of nontraumatic acute abdominal pain. She had undergone paracentesis last year with a diagnosis of suspected ascites in another medical clinic. Moreover, a CT scan following paracentesis was reported to be normal. After a few months, she gradually developed abdominal distension again. Diagnostic evaluations along with biochemical parameters and imaging strongly suggested the presence of a cyst. The large mesenteric cyst was totally removed by surgery. Conclusion: In conclusion, in the face of recurrence of abdominal fluid accumulation, mesenteric cysts should be considered despite the fact that abdominal CT scan is normal after paracentesis.

Abstract Background Irrational prescription and its subsequent costs are a major challenge worldwide. Health systems must provide appropriate conditions for the implementation of national and international strategies to prevent irrational prescription. The aim of the present study was to determine the irrational surfactant prescription among neonates with respiratory distress and the resulting direct medical costs for private and public hospitals in Iran. Methods This was a cross-sectional descriptive study performed retrospectively using data belonged to 846 patients. Initially, the data were extracted from the patients’ medical records and the information system of the Ministry of Health. The obtained data were then compared with the surfactant prescription guideline. Afterward, each neonatal surfactant prescription was evaluated based on the three filters listed in the guideline (including right drug, right dose, and right time). Finally, chi-square and ANOVA tests were used to investigate the inter-variable relationships. Results The results showed that 37.47% of the prescriptions were irrational and the average costs of each irrational prescription was calculated as 274.37 dollars. It was estimated that irrational prescriptions account for about 53% of the total surfactant prescription cost. Among the selected provinces, Tehran and Ahvaz had the worst and the best performance, respectively. As well, public hospitals outperformed private hospitals in terms of the in drug selection, but they underperformed them in terms of the right dose determination. Conclusion The results of the present study are considered as a warning to insurance organizations, in order to reduce unnecessary costs caused by these irrational prescriptions by developing new service purchase protocols. Our suggestion is the use of educational interventions to reduce irrational prescriptions due to drug selection as well as using computer alert approaches to reduce irrational prescriptions caused by wrong dose administration.

Abstract Viral hepatitis, the most common cause of inflammatory liver disease, affects hundreds of millions of people worldwide. It is most commonly associated with one of the five nominal hepatitis viruses (hepatitis A–E viruses). HBV and HCV can cause acute infections and lifelong, persistent chronic infections, while HAV and HEV cause self-limiting acute infections. HAV and HEV are predominantly transmitted through the fecal-oral route, while diseases transmitted by the other forms are blood-borne diseases. Despite the success in the treatment of viral hepatitis and the development of HAV and HBV vaccines, there is still no accurate diagnosis at the genetic level for these diseases. Timely diagnosis of viral hepatitis is a prerequisite for efficient therapeutic intervention. Due to the specificity and sensitivity of clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated sequences (Cas) technology, it has the potential to meet critical needs in the field of diagnosis of viral diseases and can be used in versatile point-of-care (POC) diagnostic applications to detect viruses with both DNA and RNA genomes. In this review, we discuss recent advances in CRISPR–Cas diagnostics tools and assess their potential and prospects in rapid and effective strategies for the diagnosis and control of viral hepatitis infection.

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.

CBCT (cone beam computed tomography) is an imaging investigation that provides three-dimensional (3D) images of craniofacial structures. The purpose of this study is to determine the mechanical behavior of an orthodontic system where the lingual treatment technique was used in a 25-year-old female patient from whom a set of CBCT scans was used. CBCT images were processed through software programs such as Invesalius, Geomagic, and Solid Works, to create models containing virtual solids. These models were then imported into Ansys Workbench 2019 R3 (a finite element method software program) for successive simulations to generate displacement maps, deformations, stress distributions, and diagrams. We observed that in the lingual technique, the lowest force occurring on the maxillary teeth is at 1.1, while the highest force appears at 2.3. In the mandible, the lowest force occurs at 4.6, and the highest force at 3.1. The values of the forces and the results of the finite element method can represent a basis for the innovation of new orthodontic springs and also of bracket elements. Thus, by using new technologies, orthodontic practice can be significantly improved for the benefit of patients. Other virtual methods and techniques can be used in future studies, including the application of virtual reality for orthodontic diagnosis.