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Investors usually hold only a small number of stocks to construct portfolio because of the cardinality constrained portfolio selection problem which arises due to the transaction cost and other market frictions. The cardinality constrained portfolio selection with the traditional mean-variance criteria (Mixed-integer and quadratic programming) and mean-CVaR (linear Mixed-integer) are an NP-Hard optimization problem. To solve this mixed-integer nonlinear programming (NP-Hard), a corresponding genetic algorithm (GA) is utilized. In this paper, we presented an algorithm that implements the model mean-CVaR as a linear model for solving this problem. Furthermore, this algorithm can be suggested all possible optimal and find the exact solution. Additionally, a numerical example, which includes an application of the algorithm by considering the stock's price of the 15 stocks, during the period from 8/16/2019 to 8/14/2020 that obtained from a real dataset, is presented in order to demonstrate that the algorithm is useful for portfolio detection. [ABSTRACT FROM AUTHOR]

Somayeh Vafaei,1–3 Fahimeh Fattahi,1,2 Marzieh Ebrahimi,3 Leila Janani,4 Ahmad Shariftabrizi,5 Zahra Madjd1,6 1Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran; 2Student Research Committee, Iran University of Medical Sciences, Tehran, Iran; 3Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; 4Department of Biostatistics, School of Public Health, Iran University of Medical Sciences, Tehran, Iran; 5Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; 6Oncopathology Research Center, Iran University of Medical Sciences, Tehran, IranCorrespondence: Zahra MadjdOncopathology Research Center, Department of Molecular Medicine, Iran University of Medical Sciences (IUMS), Hemmat Street (Highway), Next to Milad Tower, Tehran 14496-14530, IranTel +98 218 670 3212Fax +98 218 862 2608Email Zahra.madjd@yahoo.comMarzieh EbrahimiDepartment of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 16635-148, IranTel +98 2 356 2516Email mebrahimi@royaninstitute.orgAbstract: Nearly half of patients with colorectal cancer (CRC), the third leading cause of cancer deaths worldwide, are diagnosed in the late stages of the disease. Appropriate treatment is not applied in a timely manner and nearly 90% of the patients who experience metastasis ultimately die. Timely detection of CRC can increase the five-year survival rate of patients. Existing histopathological and molecular classifications are insufficient for prediction of metastasis, which limits approaches to treatment. Detection of reliable cancer-related biomarkers can improve early diagnosis, prognosis, and treatment response prediction and recurrence risk. Circulating tumor cells (CTCs) and exosomes in peripheral blood can be used in a liquid biopsy to assess the status of a tumor. Exosomes are abundant and available in all fluids of the body, have a high half-life and are released by most cells. Tumor-derived exosomes are released from primary tumors or CTCs with selective cargo that represents the overall tumor. The current systematic review highlights new trends and approaches in the detection of CRC biomarkers to determine tumor signatures using CTC and exosomes. When these are combined, they could be used to guide molecular pathology and can revolutionize detection tools. Relevant observational studies published until July 24, 2019 which evaluated the expression of tumor markers in CTCs and exosomes were searched in PubMed, Scopus, Embase, and ISI Web of Science databases. The extracted biomarkers were analyzed using String and EnrichR tools.Keywords: colorectal cancer, circulating tumor cell, CTC, exosomes, diagnosis, prognosis, biomarker, systematic review

"nBackground: Anemia is a common complication accompanied by high morbidity and mortality in hemodialysis patients. Considering the fact that the reduction of erythropoietin (EPO) synthesis is the main cause of uremic anemia, receiving recombinant human erythropoietin (rHuEPO) can improve the condition in these patients. Some of these hemodialysis patients, however, have acceptable hemoglobin levels without any need to EPO. Higher BMI, higher albumin and leptin plasma levels and longer durations of hemodialysis are possible factors contributing to the reduced need for rHuEPO in these patients. The present study is designed to asses the relationship between the plasma levels of leptin and the reduced EPO need. "nMethods: Fifty eligible hemodialysis patients with hemoglobin levels higher than 11 mg/dl were enrolled in the cross-sectional study. The information on age, sex, hemodialysis duration and the cause of renal dysfunction were extracted from the files. The baseline plasma levels of Leptin and albumin were measured. The patients BMI and the weekly need for rHuEPO were also calculated. "nResults: There was no correlation between the weekly need for rHuEPO and sex, BMI, the cause of renal dysfunction and the plasma levels of albumin and leptin; it, however, was related with age and the duration of dialysis. While age negatively influences the weekly need, the duration of dialysis has a positive effect on the need. "nConclusion: The plasma levels of leptin are not directly correlated with the required amounts of rHuEPO, indicating that leptin is not an effective factor in erythropoiesis. Conversely, older age and shorter hemodialysis durations are accompanied by reduced need for rHuEPO.

Carpal tunnel syndrome (CTS) is considered by researchers because of its high prevalence, and several studies have been done to find the causes and factors which increase the chance for the syndrome. These studies have shown relationships between this syndrome with some physical parameters like wrist dimensions, weight and systemic conditions. There is no investigation on risk factors in CTS in our country. So the main goal of this research is to find and introduce predisposing factors for carpal tunnel syndrome. Methods: Seventy patients and 33 controls 22 to 70 years old were studied. Standard methods for median and ulnar nerve studies were used and questionnaires included physical measurements, history of diseases and personal information were completed for each person. Results: Patients had higher wrist ratio (mean difference, 0.0267, P

This work presents a state-space model that can be used in the design of an egg incubator, where the objective is to control the temperature and the humidity for successful incubation. In order to get the maximum number of viable chicken eggs and healthy chicks, it is essential to use two essential parameters: temperature and humidity. The temperature plays a very important role in the hatching rate and the health of the chickens. Humidity is a necessary factor to facilitate hatching and digging, and it also affects the weight of the chick generally determining the success of incubation. The slightest difference in temperature and humidity in the incubation system can cause the failure of this operation. This work describes the Grey Wolf Optimization (GWO) algorithm as one of the new meta-heuristic algorithms adopted with the Multi-loop PID controller to control the temperature and humidity in an egg incubator. The use of the GWO algorithm is to find the best optimal parameters of the controller "Kp, Ki, Kd" using Integrated Time Absolute Error (ITAE). The simulation results show the performance of the proposed GWO optimization method compared to the control by the ant colony algorithm ACO. [ABSTRACT FROM AUTHOR]

In this paper, we study the existence of three solutions to the p(x)-Kirchhoff type equations in RN: By means of nonsmooth three critical points theorem and the theory of the variable exponent Sobolev spaces, we establish the existence of three critical points for the problem. Moreover, we study the existence of three radially symmetric solutions for a class of quasilinear elliptic inclusion problem with discontinuous nonlinearities in RN: Our approach is based on critical point theory for locally Lipschitz functionals due to Iannizzotto. [ABSTRACT FROM AUTHOR]

This study aimed to assess the frequency and severity of adverse drug reactions (ADRs) (WHO definition) in hospitalized adult patients in an infectious diseases referral ward in Tehran. Of 281 patients evaluated over 6 months, a total of 170 suspected ADRs were reported among 101 patients (35.9%). The most commonly affected organ system was gastrointestinal (47.5%), and the most common class of drugs responsible was anti-infectives (93.1%). ADRs were high among HIV-positive patients (82.9%), mainly due to anti-tuberculosis drugs. Attention to appropriate prescription of drugs is required with more careful clinical and laboratory monitoring of patients. [ABSTRACT FROM AUTHOR]

Background: Talin-1 (TLN1) is crucial in cell migration, metastasis, and cancer development. This study evaluated Talin-1 expression and its clinical significance in gastric cancer (GC), along with human epidermal growth factor receptor-2 (HER-2) expression and its correlation with Talin-1., Methods: Bioinformatics analysis assessed the potential prognostic value of Talin-1 and HER-2 in GC patients. The study included 223 GC patients (Signet Ring Cells and Intestinal subtypes) and 29 non-malignant tissue samples. Immunohistochemistry (IHC) on tissue microarray slides evaluated Talin-1 and HER-2 expression and clinical significance. Receiver operating characteristic (ROC) curves assessed their diagnostic value., Results: Bioinformatics identified Talin-1 as a potential prognostic factor and HER-2 as an oncogene in GC. Talin-1 and HER-2 expression increased in SRC-type GC samples compared to non-malignant tissues. High cytoplasmic Talin-1 expression inversely correlated with tumor expansion and invasion in SRC-type GC. Increased HER-2 expression positively correlated with metastasis. ROC curves showed significant diagnostic values for both proteins., Conclusions: Higher cytoplasmic Talin-1 expression is associated with less invasive tumor behavior, while increased membranous HER-2 expression is associated with metastasis in SRC-type GC. These findings suggest potential use in assessing diagnosis and screening high-risk cancer patients, particularly those with SRC-type GC.

Although brain amyloid-β (Aβ) peptide buildup is the main cause of Alzheimer's disease (AD), mitochondrial abnormalities can also contribute to the illness's development, as either a primary or secondary factor, as programmed cell death and efficient energy generation depend on the proper operation of mitochondria. As a result, non-coding RNAs (ncRNAs) may play a crucial role in ensuring that nuclear genes related to mitochondria and mitochondrial genes function normally. Interestingly, a significant number of recent studies have focused on the impact of ncRNAs on the expression of nucleus and mitochondrial genes. Additionally, researchers have proposed some intriguing therapeutic approaches to treat and reduce the severity of AD by adjusting the levels of these ncRNAs. The goal of this work was to consolidate the existing knowledge in this field of study by systematically investigating ncRNAs, with a particular emphasis on microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and small nucleolar RNAs (snoRNAs). Therefore, the impact and processes by which ncRNAs govern mitochondrial activity in the onset and progression of AD are thoroughly reviewed in this article. Collectively, the effects of ncRNAs on physiological and molecular mechanisms associated with mitochondrial abnormalities that exacerbate AD are thoroughly reviewed in the current research, while also emphasizing the relationship between disturbed mitophagy in AD and ncRNAs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: The exact molecular and cellular processes that cause benign urological diseases in the stromal and epithelial components of the urinary tract are yet unknown. Reviewing and analyzing the data linking microRNAs (miRNAs) expression in the pathophysiology of benign urological conditions, including overactive bladder (OAB), bladder outlet obstruction (BOO), bladder pain syndrome/interstitial cystitis (BPS/IC), and Lower urinary tract dysfunction (LUTD) is the objective of the current systematic review., Materials and Methods: Evidence including all case-control, cohort, and cross-sectional studies that measure participants' MicroRNA as a biomarker for benign urological diseases has been gathered in January 2024, through searching MEDLINE via PubMed, Scopus, Web of Science, Embase, and ProQuest databases. Studies considered eligible that present information on the reference Gene, profile type, and serum levels of microRNA from patients diagnosed with benign urological disease including benign prostate hyperplasia (BPH) or benign prostate enlargement (BPE), overactive bladder (OAB), and bladder outlet obstruction (BOO). These studies were appraised by the quality assessment checklist of Joanna Briggs Institute (JBI)., Results: A total of 4,587 records related to miRNAs in urological diseases were retrieved. Of these, we identified 28 records for our systematic study. The most frequently associated miRNA was 92a-3p identified which was found upregulated in OAB diagnosis. In BOO, miR-146a-5p was identified to be upregulated. miR-146a-5p was upregulated in BO, and for other benign conditions, different miRNAs were reported. 491-5p miRNAs were found deregulated in OAB-related studies. We expected other miRNAs to have the same trend in the OAB studies. InSUI miR-93 was the most frequent downregulated miRNA. The other reported miRNAs had similar frequencies., Conclusion: When it comes to the early detection and treatment of benign urological conditions, 92a-3p, miR-21, miR-199a-5p, and miR-146a-5p, and 491-5p have the potential to be employed as both a biomarker and a therapeutic target. The creation of pre-RNA or anti-RNA molecules within carrier vehicles that may be safely administered to patients should be made possible by technological advancements.

In polymicrobial sepsis, the extracellular histones, mainly released from activated neutrophils, significantly contribute to cardiac dysfunction (septic cardiomyopathy), as demonstrated in our previous studies using Echo-Doppler measurements. This study aims to elucidate the roles of extracellular histones and their interactions with Toll-like receptors (TLRs) in cardiac dysfunction. Through ex vivo assessments of ECG, left ventricle (LV) function parameters, and in vivo Echo-Doppler studies in mice perfused with extracellular histones, we aim to provide comprehensive insights into the mechanisms underlying sepsis-induced cardiac dysfunction. Langendorff-perfused hearts from both wild-type and TLR2, TLR3, or TLR4 knockout (KO) mice were examined. Paced mouse hearts were perfused with histones to assess contractility and relaxation. Echo-Doppler studies evaluated cardiac dysfunction after intravenous histone injection. Histone perfusion caused defects in contractility and relaxation, with TLR2 and TLR3 KO mice being partially protected. Specifically, TLR2 KO mice exhibited the greatest reduction in Echo-Doppler abnormalities, while TLR4 KO exacerbated cardiac dysfunction. Among individual histones, H1 induced the most pronounced abnormalities in cardiac function, apoptosis of cardiomyocytes, and LDH release. Our data highlight significant interactions between histones and TLRs, providing insights into histones especially H1 as potential therapeutic targets for septic cardiomyopathy. Further studies are needed to explore specific histone-TLR interactions and their mechanisms.

Introduction: Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL) in adults. Although studies regarding the association between the expression of Ki-67, CD10, BCL6, and MUM1 proteins, as well as c-MYC amplification and EBV status with clinicopathologic characteristics have rapidly progressed, their co-expression and prognostic role remain unsatisfactory. Therefore, this study aimed to investigate the association between the expression of all markers and clinicopathologic features and their prognostic value in DLBCL. Also, the co-expression of markers was investigated., Methods: The protein expression levels and prognostic significance of Ki-67, CD10, BCL6, and MUM1 were investigated with clinical follow-up in a total of 53 DLBCL specimens (including germinal center B [GCB] and activated B cell [ABC] subtypes) as well as adjacent normal samples using immunohistochemistry (IHC). Besides, the clinical significance and prognostic value of c-MYC and EBV status were also evaluated through chromogenic in situ hybridization (CISH), and their correlation with other markers was also assessed., Results: The results demonstrated a positive correlation between CD10 and BCL6 expression, with both markers being associated with the GCB subtype ( P< 0.001 and P =0.001, respectively). Besides, we observe a statistically significant association between MUM1 protein expression and clinicopathologic type ( P< 0.005) as well as a positive association between c-MYC and recurrence ( P =0.028). Our survival analysis showed that patients who had responded to R-CHOP treatment had better overall survival (OS) and progression-free survival (PFS) than those who did not., Conclusion: Collectively, this study's results add these markers' value to the existing clinical understanding of DLBCL. However, further investigations are needed to explore markers' prognostic and biological roles in DLBCL patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Statement of the Problem: Gag reflex is among the most common problems during dental and endoscopic procedures. Benzydamine hydrochloride is a non-steroidal anti-inflammatory medication and a local anesthetic that might be useful in reducing the gag reflex., Purpose: This study aimed to evaluate the effects of benzydamine hydrochloride mouthwash on the intensity of the gag reflex., Materials and Method: In this randomized clinical trial study, 30 participants aged 21-26 with a gag trigger point index (GTPI) higher than 2 were divided into 2 groups. In the case group, 15 ml of 0.15% benzydamine hydrochloride mouthwash was gargled for 1 minute, and after 10 minutes GTPI test was conducted. In the control group, 4 puffs of 10% lidocaine spray were applied to the mucosa of the targeted area, and after 5 minutes, GTPI was measured. Participants were asked about the taste and smell of the medications., Results: GTPI was significantly reduced in both groups. In the lidocaine group, the GTPI score changed from 4.47 to 2.00 ( p < 0.001), and that for the benzydamine group was 4.20 to 1.47 ( p < 0.001). The variance rate of the gag reflex was -2.73 and -2.47 in the benzydamine group and lidocaine group, respectively. However, this reduction was not statistically significant between the two groups. Moreover, benzydamine mouthwash has a significantly better taste and smell than lidocaine ( p = 0.001)., Conclusion: The results of this study showed that benzydamine mouthwash could be used quite effectively in reducing the gag reflex., Competing Interests: The authors have declared that no conflict of interest exists., (Copyright: © Journal of Dentistry.)

Background: One of the complications of multiple sclerosis (MS) is cognitive impairment (CI). The prevalence of CI is reported variously in previous studies. The goal of this systematic review and meta-analysis to estimate pooled prevalence of CI in patients with MS and also the prevalence of CI based on the type of applied test., Methods: Two independent researchers systematically searched PubMed, Scopus, EMBASE, Web of Science, and google scholar as well as gray literature (conference abstracts, references of the references) which were published before up January 2022., Results: We found 4089 articles by literature search, after deleting duplicates 3174 remained. Ninety articles remained for meta-analysis. The pooled prevalence of CI using all types of tests was 41% (95% CI: 38-44%) (I2=91.7%, p<0.001). The pooled prevalence of CI using BRB test was 39% (95%CI: 36-42%) (I2=89%, p<0.001). The pooled prevalence of CI using BICAMS was 44% (95%CI: 37-51%, I2=95.4%, p<0.001). The pooled prevalence of CI using MACFIMS was 44% (95% CI: 36-53%) (I2=89.3%, p<0.001)., Conclusions: The pooled prevalence of cognitive impairment in patients with MS is estimated as 41%, so CI it should be considered by clinicians., Competing Interests: The authors declared that they had no conflict of interest., (© The Author(s).)

The human enteric nervous system, ENS, is a large network of glial and neuronal cell types with remarkable neurotransmitter diversity. The ENS controls bowel motility, enzyme secretion, and nutrient absorption and interacts with the immune system and the gut microbiome. Consequently, developmental and acquired defects of the ENS are responsible for many human diseases and may contribute to symptoms of Parkinson's disease. Limitations in animal model systems and access to primary tissue pose significant experimental challenges in studies of the human ENS. Here, a detailed protocol is presented for effective in vitro derivation of the ENS lineages from human pluripotent stem cells, hPSC, using defined culture conditions. Our protocol begins with directed differentiation of hPSCs to enteric neural crest cells within 15 days and yields diverse subtypes of functional enteric neurons within 30 days. This platform provides a scalable resource for developmental studies, disease modeling, drug discovery, and regenerative applications.

Conventional cancer treatments can cause serious side effects because they are not specific to cancer cells and can damage healthy cells. Aptamers often are single-stranded oligonucleotides arranged in a unique architecture, allowing them to bind specifically to target sites. This feature makes them an ideal choice for targeted therapeutics. They are typically produced through the systematic evolution of ligands by exponential enrichment (SELEX) and undergo extensive pharmacological revision to modify their affinity, specificity, and therapeutic half-life. Aptamers can act as drugs themselves, directly inhibiting tumor cells. Alternatively, they can be used in targeted drug delivery systems to transport drugs directly to tumor cells, minimizing toxicity to healthy cells. In this review, we will discuss the latest and most advanced approaches to using aptamers for cancer treatment, particularly targeted therapy overcoming resistance to conventional therapies., (© 2024. The Author(s).)