Prediction of chromosomal abnormalities in the screening of the first trimester of pregnancy using machine learning methods: a study protocol.

BACKGROUND: For women in the first trimester, amniocentesis or chorionic villus sampling is recommended for screening. Machine learning has shown increased accuracy over time and finds numerous applications in enhancing decision-making, patient care, and service quality in nursing and midwifery. This study aims to develop an optimal learning model utilizing machine learning techniques, particularly neural networks, to predict chromosomal abnormalities and evaluate their predictive efficacy. METHODS/ DESIGN: This cross-sectional study will be conducted in midwifery clinics in Mashhad, Iran in 2024. The data will be collected from 350 pregnant women in the high-risk group who underwent screening tests in the first trimester (between 11-14 weeks) of pregnancy. Information collected includes maternal age, BMI, smoking habits, history of trisomy 21 and other chromosomal disorders, CRL and NT levels, PAPP-A and B-HCG levels, presence of insulin-dependent diabetes, and whether the pregnancy resulted from IVF. The study follows up with the women during their clinic visits and tracks the results of amniocentesis. Sampling is based on Convenience Sampling, and data is gathered using a checklist of characteristics and screening/amniocentesis results. After preprocessing, feature extraction is conducted to identify and predict relevant features. The model is trained and evaluated using K-fold cross-validation. DISCUSSION: There is a growing interest in utilizing artificial intelligence methods, like machine learning and deep learning, in nursing and midwifery. This underscores the critical necessity for nurses and midwives to be well-versed in artificial intelligence methods and their healthcare applications. It can be beneficial to develop a machine learning model, specifically focusing on neural networks, for predicting chromosomal abnormalities. ETHICAL CODE: IR.MUMS.NURSE.REC. 1402.134.

Approximately 3% of newborns are affected by congenital abnormalities and genetic diseases, leading to disability and death. Among live births, around 3000 cases of Down syndrome (trisomy 21) can be expected based on the country's birth rate. Pregnant women carrying fetuses with Down syndrome face an increased risk of pregnancy complications. Artificial intelligence methods, such as machine learning and deep learning, are being used in nursing and midwifery to improve decision-making, patient care, and research. Nurses need to actively participate in the development and implementation of AI-based decision support systems. Additionally, nurses and midwives should play a key role in evaluating the effectiveness of artificial intelligence-based technologies in professional practice.

An Update on the Application of CRISPR Technology in Clinical Practice.

The CRISPR/Cas system, an innovative gene-editing tool, is emerging as a promising technique for genome modifications. This straightforward technique was created based on the prokaryotic adaptive immune defense mechanism and employed in the studies on human diseases that proved enormous therapeutic potential. A genetically unique patient mutation in the process of gene therapy can be corrected by the CRISPR method to treat diseases that traditional methods were unable to cure. However, introduction of CRISPR/Cas9 into the clinic will be challenging because we still need to improve the technology's effectiveness, precision, and applications. In this review, we first describe the function and applications of the CRISPR-Cas9 system. We next delineate how this technology could be utilized for gene therapy of various human disorders, including cancer and infectious diseases and highlight the promising examples in the field. Finally, we document current challenges and the potential solutions to overcome these obstacles for the effective use of CRISPR-Cas9 in clinical practice.

Experimental investigation and simultaneous modeling of the effect of methylene blue addition to cancer tumors in photodynamic therapy by digital holography.

BACKGROUND: Although many types of cancers can be treated with surgery, alternatives such as photodynamic therapy with simultaneous use of photosensitive materials and illumination can also be used. Knowing the dose of absorbed energy from the light beam in the photo-sensitized tumors and tissues has an important role in designing the optimal irradiation method with the aim of investigating the amount of received damage to the healthy and tumor tissues. METHODS: In this study, the effect of the presence of methylene blue sensitizer on the amount of dose received in tissue-equivalent material has been investigated experimentally by Mach-Zehnder interferometry and digital holography. The Monte Carlo method and the ValoMC code have been used to confirm the results obtained in the experimental phase. RESULTS: The results indicate the positive role of methylene blue in increasing the absorbed dose of tumor-equivalent material. The amount of light dose increase and the two-dimensional profile of the dose absorbed in tissue and tumor equivalent materials have been measured by digital holography. CONCLUSIONS: The method presented in this work can be used in treatment design and real time measuring of the spatially resolved distribution of the absorbed dose in the tissues containing tumors.

Role of miRNA gene variants in the susceptibility and pharmacogenetics of colorectal cancer.

Colorectal cancer (CRC) is one of the most significant challenges in the field of cancer pathology. miRNAs are among the genetic factors associated with the disease. Although many studies have reviewed the expression patterns of various miRNAs in CRC, few studies have focused on different variants of miRNA. In the present review, miRNA variants have been categorized into three subgroups, including miRNA variants that predict susceptibility to CRC, miRNA variants that predict the clinical parameters of CRC and finally, miRNA variants that predict the pharmacological aspects of CRC. Moreover, a comprehensive review of potentially functional miRNA-associated SNPs as well as their importance as candidate cancer biomarkers are discussed.

Differentiation Induction and Proliferation Inhibition by A Cell-Free Approach for Delivery of Exogenous miRNAs to Neuroblastoma Cells Using Mesenchymal Stem Cells.

OBJECTIVE: Neuroblastoma (NB) is one of the frequently observed malignant solid tumors of childhood and infancy, accounting for 15% of pediatric cancer deaths. Recently, the approach of differentiation therapy has shown considerable promise in effective treatment of NB patients. MiR-124 belongs to the nervous system-specific miRNAs that is increased during neuronal differentiation and may be one of the potential therapeutic targets for the treatment of NB. However, despite its well-established therapeutic potential, its efficient delivery to the targeted tumor cells is a challenging task. Mesenchymal stem cells (MSCs) are multipotent adult progenitor cells that have antitumor properties, and they can migrate to cancer cells and tumors. This study aimed to assess whether human adipose tissue-derived MSCs (hADMSCs) have the potential to deliver exogenous miRNAs to NB cells to induce differentiation and decrease proliferation of cancer cells. MATERIALS AND METHODS: In this experimental study, hAD-MSCs were isolated, cultured, and differentiated. The M17 human NB cell line were also cultured. A specific type of miRNAs, i.e., miR-124 was successfully delivered to M17 NB cells with the aid of hAD-MSCs using the direct or indirect (exosome-based) contacts. RESULTS: It was shown that indirect delivery of miR-124 considerably decreased the proliferation of NB cells and induced their differentiation. CONCLUSION: The results suggest the use of delivered exogenous miRNAs by the derived exosomes from hAD-MSCs as a novel cell-free stem cell-based therapy for NB cancer.

Traditional Yellow Dyes Used in the 21st Century in Central Iran: The Knowledge of Master Dyers Revealed by HPLC-DAD and UHPLC-HRMS/MS.

This work provides new knowledge on natural yellows used in Iran. Seven biological sources were selected based on interviews with dye masters in Isfahan workshops (Iran). Delphinium semibarbatum, Eremostachys laevigata, Prangos ferulacea, Morus alba, Pistacia vera, Punica granatum, and Vitis vinifera are currently used in these workshops. Aiming to study the dye composition of wool samples dyed with the extracts of the selected biological sources and the changes induced by the dyeing procedures in the original chemical composition of the plant extract, raw materials and dyed wool (by us and in the workshops) were analyzed by HPLC-DAD and UHPLC-HRMS/MS. The main yellows for E. laevigata are luteolin-O-glycosides. In the other plant sources, the main chromophores are based on 3-O-glycosides of kaempferol, quercetin, and isorhamnetin. In pistachio hulls, myricitin derivatives were detected and we propose their use as markers. Generally, the solutions extracted from the wool displayed a higher amount of more polar compounds, but also a higher amount of aglycones. Importantly, the chromatographic profiles of the samples we prepared compared well with 17th c. yellows in Persian carpets, and therefore can be considered highly characterized references for the study of Persian yellows.

A New Optical Method for Online Monitoring of the Light Dose and Dose Profile in Photodynamic Therapy.

BACKGROUND AND OBJECTIVES: Photodynamic therapy (PDT) has gained widespread popularity in the last decades because of its distinctive advantages over the other commonly used cancer treatments. PDT dosimetry is a crucial factor in achieving a good optimization of PDT treatment planning. PDT dosimetry is a complex task since light dose as well as photosensitizer and oxygen concentrations in tissue need to be measured (ideally continuously) to be able to fully characterize the biological response. Light dose in PDT is routinely measured by the optical fibers that provide dose data at a limited number of discrete points and are not able to capture spatial dose profiles. The objective of this study is to propose and develop a new optical method for online monitoring of the dose profile data for PDT. STUDY DESIGN/MATERIALS AND METHODS: Using the digital holography technique, first, the general sketch of an experimental setup for PDT light dosimetry is provided. The theory behind the proposed method for using the experimental setup in PDT light dosimetry is fully described, and its limits of validity are determined. In a proof of principle study, the ability of the method for online monitoring of the absorbed light dose profile in PDT is evaluated by a simple experimental setup. RESULTS: The experimental results confirm the usefulness of the proposed method in providing continuous online dose profiles. The absorbed light dose profiles from an infrared light source in a quartz cell containing water are measured and shown. The depth-dose curves are extracted and it is shown that how these dosimetric data can be used for assisting the physicians in determining the appropriate spatiotemporal characteristics for treating the infected tissues and solid tumors with the required light dose amounts. A conversion relation is also derived for transforming the measured light dose with the proposed method to the most frequently used dose values by PDT practitioners, in terms of light power per square area. CONCLUSIONS: There is no restriction in using the method with other commonly used light sources in PDT, like light-emitting diodes and filtered lamps, with different wavelengths in visible or infrared regions of the spectrum. More complex experimental setups can be used in future studies to study the role of accumulated photosensitizers in malignant tissues. The proposed method in this study can also be used for light dose monitoring in other biomedical applications, where light is used for treating special diseases, and patients must receive sufficient amounts of light dose. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Induction of morphological and functional differentiation of human neuroblastoma cells by miR-124.

Neuroblastoma is the most common extracranial solid tumour in children, and differentiation is considered its most appropriate therapy. In this work, we studied effects of miR-124 overexpression on differentiation in M17 cell line as a model of neuroblastoma cancer. Influence of miR-124 overexpression on differentiation in M17 cells was studied. M17 cells were infected with lentivirus that contained miR-124 precursor sequence and followed for 2 weeks to differentiate. Ectopic expression of miR-124 in M17 cells changed the shape of spherical undifferentiated cells to cells with extended neurites that formed neuronal networks. Overexpression of MiR-124 respectively increased the expression level of markers of ß-Tubulin III, MAP2, SYN, NF-M and Nestin by 16-, 5-, 4-, 2.3- and 2-folds at the messenger RNA level. MiR-124 overexpression also increased the protein levels of ß-Tubulin III and MAP2. Moreover, exogenous expression of miR-124 significantly increased the intracellular calcium in differentiated M17 cells. Since miR-124 is naturally expressed in neuronal cells and is downregulated in neuroblastoma cancer cells, differentiation with this type of microRNA can be a novel treatment for neuroblastoma cancer.

Immunohistochemical assessment of MGMT expression and p53 mutation in glioblastoma multiforme.

AIMS AND BACKGROUND: The prognosis of glioblastoma multiforme (GBM) remains poor despite advances in surgery and adjuvant therapies. TP53 and O6-methylguanine-DNA methyltransferase (MGM) are tumor suppressor genes that are implicated in GBM resistance to radiation and chemotherapy. In order to assess the expression of the protein products of these two genes, 50 GBM samples were analyzed in this study. METHODS: Demographic and clinical data along with postsurgery tumor samples from 50 GBM patients were collected from the pathology archive. MGMT and p53 protein expression was evaluated by immunohistochemistry. RESULTS: 52% of cases had mutated p53, predominantly expressed in the nuclei of tumor cells. MGMT immunohistochemistry was negative in 35 (70%) patients and positive in 15 (30%) others. Immunohistochemistry-negative specimens for MGMT expression showed a significantly higher expression of mutant p53 (P = 0.03). CONCLUSION: MGMT expression was significantly lower in cells bearing p53 mutation. This indicates that there is a tendency for p53 activity to decline with MGMT inactivation. However, this study could not deduce which protein was the regulator of the other.

Association between MGMT promoter hypermethylation and p53 mutation in glioblastoma.

O(6)-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme that removes alkyl groups from the O(6) position of guanine. MGMT is transcriptionally silenced by promoter hypermethylation in several human neoplasia. We used methylation-specific PCR (MSP) to analyze the MGMT promoter methylation status of 50 glioblastoma tumors. Hypermethylation was detected in 24 of 50 (48%) samples. We also analyzed mutant p53 expression by immunohistochemical analysis of glioblastoma tissue samples. A significant association was found between MGMT methylation and p53 mutation status (p< .05). These results suggested that epigenetic inactivation of MGMT plays an important role in the survival of glioblastoma patients and this inactivated gene involved in p53 mutation.