Predicting the conversion from clinically isolated syndrome to multiple sclerosis: An explainable machine learning approach.

INTRODUCTION: Predicting the conversion of clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) is critical to personalizing treatment planning and benefits for patients. The aim of this study is to develop an explainable machine learning (ML) model for predicting this conversion based on demographic, clinical, and imaging data. METHOD: The ML model, Extreme Gradient Boosting (XGBoost), was employed on the public dataset of 273 Mexican mestizo CIS patients with 10-year follow-up. The data was divided into a training set for cross-validation and feature selection, and a holdout test set for final testing. Feature importance was determined using the SHapley Additive Explanations library (SHAP). Then, two experiments were conducted to optimize the model's performance by selectively adding variables and selecting the most contributive variables for the final model. RESULTS: Nine variables including age, gender, schooling, motor symptoms, infratentorial and periventricular lesion at imaging, oligoclonal band in cerebrospinal fluid, lesion and symptoms types were significant. The model achieved an accuracy of 83.6 %, AUC of 91.8 %, sensitivity of 83.9 %, and specificity of 83.4 % in cross-validation. In the final testing, the model achieved an accuracy of 78.3 %, AUC of 85.8 %, sensitivity of 75 %, and specificity of 81.1 %. Finally, a web-based demo of the model was created for testing purposes. CONCLUSION: The model, focusing on feature selection and interpretability, effectively stratifies risk for treatment decisions and disability prevention in MS patients. It provides a numerical risk estimate for CDMS conversion, enhancing transparency in clinical decision-making and aiding in patient care.

Congenital Heart Defects in Pregnancies Conceived by Assisted Reproductive Technology: Comparing Functional and Structural Defects.

Introduction Congenital heart defects (CHD) are one of the most common congenital anomalies, and their association with assisted reproductive technology (ART) is controversial in different populations. The purpose of this study was to evaluate this association and to provide information about the necessity of specialized echocardiography during pregnancy with ART. Methods This retrospective study was performed on all pregnancies conceived by ART and referred for fetal echocardiography to the Rasoul Akram and Akbar Abadi hospitals in Tehran, Iran. A total of 109 patients were enrolled in the study (56 in the ART group and 53 in the non-ART). Two-dimensional and color Doppler echocardiography were performed on all patients to identify heart problems and anomalies and medical records of the patients were reviewed. The outcome was considered the presence of functional and structural heart defects on echocardiography. Results The study groups were similar in terms of maternal age and GA. The ART group consisted of 31 singletons (55%) and 25 multiples (45%). All pregnancies in the non-ART group were singletons. Following in vitro fertilization (33%), ovulation induction (25%) was the next most used method. The findings of echocardiography were one atrial septal defect (ASD) in ART and one in non-ART, six ventricular septal defects (VSD) in ART and three in non-ART, and one ASD and VSD in the ART group. These structural abnormalities showed no difference in the two groups (P value = 0.58). There was no significant difference in rhythm between the two groups (P = 0.51). Echocardiographic indices of both groups did not differ statistically except in the TR-PG index (P value = 0.02). Conclusions The structural defects of the two groups were not different, and no heart dysfunction was observed in ART fetuses. There was no association between ART and CHD in our study. We concluded that echocardiography by pediatric cardiologists is not necessary for these fetuses.

Evaluating the application of argon laser on pterygium surgery: Report of 30 patients.

BACKGROUND: The recurrence rate plays a key role in using various treatments of pterygium. This study assessed the effectiveness of argon laser therapy before the excision of pterygium on the recurrence rate. MATERIALS AND METHODS: The eyes (n = 60) of patients (n = 30) were divided into two groups based on the treatment. All eyes had undergone pterygium excision with the bare sclera technique. Three weeks before surgery, an argon laser was applied to 30 eyes. Patients have been followed up for 1 year, and the progression of pterygium has been evaluated at days 1, 7, 14, and 30, and then, every 2 months until month 6 and then every 3 months until month 12. Recurrence was defined as more than 1 mm growth of pterygium from the limbus. RESULTS: In the group with adjuvant argon laser therapy, the mean size of pterygium was 3.7 ± 0.47 mm before surgery and 2.3 ± 0.98 after 12 months (P = 0.001). These were 3.8 ± 0.43 mm and 2.4 ± 1 mm in the other group (P = 0.001). The recurrence of the pterygium was 76% (23/30) in the group treated with an argon laser and 90% (27/30) in another group (P = 0.16). There was no correlation between pterygium sizes before surgery and the pterygium recurrence rate in both eyes (P = 0.272 [right] and 0.916 [left]). CONCLUSION: Argon laser therapy on pterygium before surgery cannot decrease its recurrence rate, but its application gives a good vision and clarifies the surgery's target area.

Efficacy and safety of miglustat in the treatment of GM2 gangliosidosis: A systematic review.

BACKGROUND: Since the results of previous studies regarding the safety and efficacy of miglustat in GM2 gangliosidosis (GM2g) were inconsistent, we aimed to assess miglustat therapy in GM2g patients. METHODS: This study followed the latest version of PRISMA. We included the observational or interventional studies reporting GM2g patients under miglustat therapy by searching PubMed, Web of Science, and Scopus. Data extracted included the natural history of individual patient data, as well as the safety and efficacy of miglustat in GM2g patients. The quality assessment was performed using the Joanna Briggs Institute Critical Appraisal checklist. RESULTS: A total of 1023 records were identified and reduced to 621 after removing duplicates. After screening and applying the eligibility criteria, 10 articles and 2 abstracts met the inclusion criteria. Overall, the studies represented 54 patients with GM2g under treatment with miglustat and 22 patients with GM2g in the control group. Among patients with available data, 14 and 54 have been diagnosed with Sandhoff disease and Tay-Sachs disease, respectively. Patients included in this review consisted of 23 infantile, 4 late-infantile, 18 juvenile, and 31 adult-onset GM2g. CONCLUSIONS: Although miglustat should not be considered a definite treatment for GM2g, it appears that patients, particularly those with infantile or late-infantile GM2g, could benefit from miglustat therapy to some extent. We also make some suggestions regarding future studies presenting their findings in a standard format to facilitate pooling the available data in such rare diseases for a more comprehensive conclusion.

Induction of Cancer Cell Death by Apigenin: A Review on Different Cell Death Pathways.

Induction of cell death and inhibition of cell proliferation in cancer have been set as some of the main goals in anti-tumor therapy. Cancer cell resistance leads to less efficient cancer therapy, and consequently, to higher doses of anticancer drugs, which may eventually increase the risk of serious side effects in normal tissues. Apigenin, a nature-derived and herbal agent, which has shown anticancer properties in several types of cancer, can induce cell death directly and/or amplify the induction of cell death through other anti-tumor modalities. Although the main mechanism of apigenin in order to induce cell death is apoptosis, other cell death pathways, such as autophagic cell death, senescence, anoikis, necroptosis, and ferroptosis, have been reported to be induced by apigenin. It seems that apigenin enhances apoptosis by inducing anticancer immunity and tumor suppressor genes, like p53 and PTEN, and also by inhibiting STAT3 and NF-κB signaling pathways. Furthermore, it may induce autophagic cell death and ferroptosis by inducing endogenous ROS generation. Stimulation of ROS production and tumor suppressor genes, as well as downregulation of drug-resistance mediators, may induce other mechanisms of cell death, such as senescence, anoikis, and necroptosis. It seems that the induction of each type of cell death is highly dependent on the type of cancer. These modulatory actions of apigenin have been shown to enhance anticancer effects by other agents, such as ionizing radiation and chemotherapy drugs. This review explains how cancer cell death may be induced by apigenin at the cellular and molecular levels.

Resveratrol in Cancer Therapy: From Stimulation of Genomic Stability to Adjuvant Cancer Therapy: A Comprehensive Review.

Cancer therapy through anticancer drugs and radiotherapy is associated with several side effects as well as tumor resistance to therapy. The genotoxic effects of chemotherapy and radiotherapy may lead to genomic instability and increased risk of second cancers. Furthermore, some responses in the tumor may induce the exhaustion of antitumor immunity and increase the resistance of cancer cells to therapy. Administration of low-toxicity adjuvants to protect normal tissues and improve therapy efficacy is an intriguing strategy. Several studies have focused on natural-derived agents for improving the antitumor efficiency of radiotherapy, chemotherapy, and novel anticancer drugs such as immunotherapy and targeted cancer therapy. Resveratrol is a naturally occurring substance with intriguing antioxidant, cardioprotective, anti-diabetes, and antitumor properties. Resveratrol has been demonstrated to modulate tumor resistance and mitigate normal tissue toxicity following exposure to various drugs and ionizing radiation. Compelling data suggest that resveratrol may be an appealing adjuvant in combination with various anticancer modalities. Although the natural form of resveratrol has some limitations, such as low absorption in the intestine and low bioavailability, several experiments have demonstrated that using certain carriers, such as nanoparticles, can increase the therapeutic efficacy of resveratrol in preclinical studies. This review highlights various effects of resveratrol that may be useful for cancer therapy. Consequently, we describe how resveratrol can protect normal tissue from genomic instability. In addition, the various mechanisms by which resveratrol exerts its antitumor effects are addressed. Moreover, the outcomes of combination therapy with resveratrol and other anticancer agents are reviewed.

Paroxysmal hemicrania in children and adolescents: A systematic review.

OBJECTIVE: We aimed to report the accessible demographic, clinical, and radiological characteristics of reported pediatric paroxysmal hemicrania (PH). INTRODUCTION: It has been a while since PH in a child was first described. However, it is still unknown whether children's PH follows the same patterns as adults. METHODS: This study followed the latest version of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). PubMed, Web of Science, and Scopus were searched systematically without time limitation. We included all English-language, peer-reviewed articles, including observational or interventional studies reporting PH cases in children or adolescents based on the International Classification of Headache Disorders (ICHD) criteria. Data extracted included PH class; sex; age; age of onset; frequency, duration, site, severity, and quality of pains; triggers; and autonomic and migrainous symptoms, as well as a sense of restlessness/agitation, response to treatment, laboratory investigations, imaging, comorbidity, and family history. For quality assessment, two independent reviewers (MB and VM) assessed the methodological quality of the included studies through the Joanna Briggs Institute's critical appraisal checklist. RESULTS: A total of 182 records were identified and reduced to 116 after removing duplicates. After screening, 22 articles met the inclusion criteria. Overall, the studies represented 35 children or adolescents with PH. We found a boy-to-girl ratio of 1.125:1. Onset occurred at a broad range of 1 to 14 years old. The mean age of onset among reported cases in children and adolescents was 6.5 years, while the mean age of diagnosis was 8.2 years. [Correction added on 22 August 2022, after first online publication: In the preceding sentence, 6.3 and 7.9 years were changed to 6.5 and 8.2 years, respectively.] The attacks' frequency and duration were greatly varied. Left-sided pain occurred twice as often as right-sided pain. The characteristics of the pain were usually severe in intensity. In nearly all of the cases, it was accompanied by ipsilateral cranial autonomic features. While most attacks were spontaneous, there were some common triggers. The physical examination, electroencephalogram, and brain magnetic resonance imaging had normal findings. Almost all patients benefited from indomethacin and showed complete responses to treatment, while some needed combination treatment of indomethacin with other medications. CONCLUSION: Although pediatric-onset PH has similar features to adult-onset PH, there are some challenges with ICHD criteria for younger children that limit the ability to confidently assign a diagnosis. Moreover, owing to concomitant migrainous features, PH may be confused with migraine in children and adolescents.

Modulation of the immune system by melatonin; implications for cancer therapy.

Immune system interactions within the tumour have a key role in the resistance or sensitization of cancer cells to anti-cancer agents. On the other hand, activation of the immune system in normal tissues following chemotherapy or radiotherapy is associated with acute and late effects such as inflammation and fibrosis. Some immune responses can reduce the efficiency of anti-cancer therapy and also promote normal tissue toxicity. Modulation of immune responses can boost the efficiency of anti-tumour therapy and alleviate normal tissue toxicity. Melatonin is a natural body agent that has shown promising results for modulating tumour response to therapy and also alleviating normal tissue toxicity. This review tries to focus on the immunomodulatory actions of melatonin in both tumour and normal tissues. We will explain how anti-cancer drugs may cause toxicity for normal tissues and how tumours can adapt themselves to ionizing radiation and anti-cancer drugs. Then, cellular and molecular mechanisms of immunoregulatory effects of melatonin alone or combined with other anti-cancer agents will be discussed.

Folic Acid-Decorated pH-Responsive Nanoniosomes With Enhanced Endocytosis for Breast Cancer Therapy: In Vitro Studies.

Breast cancer is the most common invasive cancer in women and the second leading cause of cancer death in women after lung cancer. The purpose of this study is a targeted delivery toward in vitro (on MCF7 and 4T1 breast cancer cell lines) through niosomes-based nanocarriers. To this end, different bioactive molecules, including hyaluronic acid (HA), folic acid (FA), and polyethylene glycol (PEG), were used and compared for surface modification of niosomes to enhance endocytosis. FA-functionalized niosomes (Nio/5-FU/FA) were able to increase cell cytotoxicity and reduce cell migration and invasion compared to PEG-functionalized niosomes (Nio/5-FU/PEG), and HA-functionalized niosomes (Nio/5-FU/HA) groups in MCF-7 and 4T1 cell lines. Although the Nio/5-FU/PEG and Nio/5-FU/HA demonstrated MCF7 cell uptake, the Nio/5-FU/FA exhibited the most preponderant endocytosis in pH 5.4. Remarkably, in this study 5-FU loaded niosomes (nonionic surfactant-based vesicles) were decorated with various bioactive molecules (FA, PEG, or HA) to compare their ability for breast cancer therapy. The fabricated nanoformulations were readily taken up by breast cancer cells (in vitro) and demonstrated sustained drug release characteristics, inducing cell apoptosis. Overall, the comprehensive comparison between different bioactive molecules-decorated nanoniosomes exhibited promising results in finding the best nano formulated candidates for targeted delivery of drugs for breast cancer therapy.

Evaluation of the Association between Fetal Cardiac Disorders with Choroid Plexus Cyst in Fetuses.

Choroid plexus cysts (CPCs) are often transient and benign findings observed in pregnancy screenings. This study aimed to examine the association between the frequency of congenital heart diseases and the detection of CPCs. In this prospective case-control study, pregnant mothers with no predisposing risk factors for the development of fetal cardiac abnormalities were eligible for entry. Based on the presence or absence of CPCs on ultrasound, the enrolled fetuses were divided into two groups. All patients (n = 100) underwent two-dimensional and color Doppler echocardiography to identify potential cardiac anomalies. Overall, CPCs were detected in 53 enrolled fetuses, and the remainder were enrolled as controls (n = 47). Pathological findings, such as echogenic intracardiac focus (EIF), ductal spasm, atrial septal defect (ASD), pericardial effusion, cardiomyopathy, and congenital heart disease were found in neither group. In the CPC group, two mild and six trivial cases of tricuspid regurgitation (TR) were detected. In the controls, five cases of trivial TR were identified. In conclusion, the presence of CPCs was not associated with significant functional or structural fetal cardiac abnormalities, which may be due to altered developmental mechanisms.