A Method for Predicting Production Costs Based on Data Fusion from Multiple Sources for Industry 4.0: Trends and Applications of Machine Learning Methods.

There is a growing need for manufacturing processes that improve product quality and production rates while reducing costs. With the advent of multisensory information fusion technology, individuals can acquire a broader range of information. Several data fusion and machine learning methods have been discussed in this article within the context of the Industry 4.0 paradigm. Depending on its purpose, a prognostic method can be categorized as descriptive, predictive, or prescriptive. ANN and CNN models are applied to predicting production costs using neural networks based on multisource information fusion, and multisource information fusion theory is examined and applied to ANNs and CNNs. In this study, ANN and CNN predictions have been compared. CNN has demonstrated more remarkable skill in predicting the six cost categories than ANN. When predicting the true value of each cost category, CNN is superior to ANN. As a result, CNN's forecast error for the current month's total income is 0.0234. Because of its improved prediction accuracy and more straightforward training technique, CNN is better suited to incorporating information from several sources. Furthermore, both neural networks overestimate indirect costs, including direct material costs and item consumption prices.

Report of a phase 1 clinical trial for safety assessment of human placental mesenchymal stem cells therapy in patients with critical limb ischemia (CLI).

BACKGROUND: Critical limb ischemia (CLI) is associated with increased risk of tissue loss, leading to significant morbidity and mortality. Therapeutic angiogenesis using cell-based treatments, notably mesenchymal stem cells (MSCs), is essential for enhancing blood flow to ischemic areas in subjects suffering from CLI. The objective of this study was to evaluate the feasibility of using placenta-derived mesenchymal stem cells (P-MSCs) in patients with CLI. METHODS: This phase I dose-escalation study investigated P-MSCs in nine CLI patients who were enrolled into each of the two dosage groups (20 × 106 and 60 × 106 cells), delivered intramuscularly twice, two months apart. The incidence of treatment-related adverse events was the primary endpoint. The decrease in inflammatory cytokines, improvement in the ankle-brachial pressure index (ABI), maximum walking distance, vascular collateralization, alleviation of rest pain, healing of ulceration, and avoidance of major amputation in the target leg were the efficacy outcomes. RESULTS: All dosages of P-MSCs, including the highest tested dose of 60 × 106 cells, were well tolerated. During the 6-month follow-up period, there was a statistically significant decrease in IL-1 and IFN-γ serum levels following P-MSC treatment. The blood lymphocyte profile of participants with CLI did not significantly differ, suggesting that the injection of allogeneic cells did not cause T-cell proliferation in vivo. We found clinically substantial improvement in rest pain, ulcer healing, and maximum walking distance after P-MSC implantation. In patients with CLI, we performed minor amputations rather than major amputations. Angiography was unable to demonstrate new small vessels formation significantly. CONCLUSION: The observations from this phase I clinical study indicate that intramuscular administration of P-MSCs is considered safe and well tolerated and may dramatically improve physical performance and minimize inflammatory conditions in patients with CLI. TRIAL REGISTRATION: IRCT, IRCT20210221050446N1. Registered May 09, 2021.

Intracerebral Administration of Autologous Mesenchymal Stem Cells as HSV-TK Gene Vehicle for Treatment of Glioblastoma Multiform: Safety and Feasibility Assessment.

Widespread investigation has revealed the promising ability of suicidal genes in the treatment of glioma tumors; nevertheless, promoting their effects relies on the ability to apply suitable vehicles and techniques. In this study, the safety and feasibility of using bone marrow-derived mesenchymal stem cells (MSCs) in combination with prodrug for treatment of patients with primary and secondary glioblastoma multiform (GBM) was assessed. Five GBM patients were recruited. Following gross total resection of the tumor and adjuvant radiotherapy and chemotherapy, intracerebral injection of autologous MSCs transduced with lentivirus containing herpes simplex virus thymidine kinase (HSV-TK) was performed followed by intravenous administration of ganciclovir for 2 weeks. The treatment was well tolerated by all patients. Mild-to-moderate fever, headache, and cerebrospinal fluid leukocytosis were evident in three, two, and one patient, respectively. The progression-free survival (PFS) and overall survival (OS) of patients were 95.79 ± 51.40 and 128.85 ± 48.81 weeks, respectively. The 1-year PFS and OS were 60% and 100%, respectively, among our patients, and two patients had more than 3 years of OS and more than 2 years of PFS. It seems that intracerebral administration of bone marrow MSC containing the HSV-TK gene in combination with intravenous ganciclovir would be safe and feasible in the treatment of patients with GBM.

A simple and cost-effective method for isolation and expansion of human fetal pancreas derived mesenchymal stem cells.

BACKGROUND: Previous studies have suggested mesenchymal stem cells (MSCs) as a suitable source for cell replacement therapy in diabetes. MSCs have successfully isolated from different adult and fetal tissues, including the pancreas. In vitro studies have shown that human fetal pancreatic stem cells could be extensively expanded and differentiated into islet-like structures. Here, we introduce a simple and cost-effective method for the generation of MSCs from the human fetal pancreas (FPMSCs). METHODS: To isolate FPMSCs, pancreata from four aborted fetuses (second trimester) were processed with short collagenase digestion. The resulting tissue fragments were transferred to a basic media (DMEM+15%FBS) without adding any growth factor. RESULTS: After 10 to14 days, fibroblast-like cells were harvested and passaged six times for further evaluations. Flow cytometry analysis and three-lineage differentiation capacity have demonstrated that these cells have MSC-like properties. We also continuously passaged samples of FPMSCs and found no evidence for chromosomal instability and morphological changes until 10th subculture. Moreover, our cell culture protocol can be easily modified and translated into a GMP-compliant one. CONCLUSION: The results of current study demonstrated that our simple and inexpensive method could yield a pure population of FPMSCs that might be suitable for transplantation.

Efficient lentiviral transduction of adipose tissue-derived mouse mesenchymal stem cells and assessment of their penetration in female mice cervical tumor model.

BACKGROUND: Although the incidence of cervical cancer has reduced during last years, but it causes mortality among women. Many efforts have performed to develop new drugs and strategy for treatment of cervical cancer. Adipose Tissue-Derived mouse Mesenchymal Stem Cells (MSCs) has many advantages which make them a suitable choice as a cell therapeutic agent in cancer treatment. In this study, we aimed to develop an improved protocol for Mouse MSCs transduction as well as assess the homing capacity and incorporation of MSCs in cervical cancer model. METHODS: MScs were isolated from the mouse adipose tissue and characterized by differentiation and flow cytometry. In our study, lentiviral vector transductions of MSCs performed. Their penetrations were detected in tissue sections after injection of transduced MSCs to female C57BL/6 mice as a cervical cancer model. RESULTS: Results showed that MSCs were efficiently transduced with lentiviral vector resulting in efficient tumor penetration. CONCLUSION: The results provide evidence that MSCs were able to penetrate into the tumor mass of cervical tumor model and are good vehicles for gene transfer to cervical cancer.

Safety and possible outcome assessment of autologous Schwann cell and bone marrow mesenchymal stromal cell co-transplantation for treatment of patients with chronic spinal cord injury.

BACKGROUND AIMS: Cell replacement therapy has become a promising issue that has raised much hope in the regeneration of central nervous system injury. Evidence indicates that successful functional recovery in patients with spinal cord injury will not simply emphasize a single therapeutic strategy. Therefore, many recent studies have used combination strategies for spinal cord regeneration. METHODS: We assessed the safety and feasibility of a bone marrow mesenchymal stromal cell and Schwann cell combination for the treatment of patients with chronic spinal cord injury. Eight subjects who received a complete traumatic spinal cord injury (American Spinal Injury Association [ASIA] classification A) enrolled in this study. The patients received this autologous combination of cells directly into the injury site. The mean duration of follow-up was approximately 24 months. RESULTS: No magnetic resonance imaging evidence of neoplastic tissue overgrowth, syringomyelia or psuedomeningocele in any of the patients was seen during the study. There was no deterioration in sensory or motor function in any of the patients during the course of the study. Three patients had negligible improvement in ASIA sensory scale. No motor score improvement and no change in ASIA classification was seen. The patients had widely subjective changes in the course of the study such as urination and defecation sensation and more stability and trunk equilibrium in the sitting position. CONCLUSIONS: There were no adverse findings at least 2 years after autologous transplantation of Schwann cell and mesenchymal stromal cell combination into the injured spinal cord. It appears that the use of this combination of cells is safe for clinical application to spinal cord regeneration.

Development of a robust, low cost stem-loop real-time quantification PCR technique for miRNA expression analysis.

Development of a rapid and accurate quantification method for the detection of microRNAs (miRNAs) has been desired, in particular, when they are differently expressed in normal and pathological conditions. However, various methods for the quantification of small non-coding RNAs as well as miRNAs have been described. These methods mainly include hybridization-based approaches such as primer extension, northern blotting, microarray profiling, and reverse transcription (RT) PCR. Here, we developed a simple and rapid method based on stem-loop primer-based real-time PCR assay for sensitive and accurate detection of mature miRNAs. Initially, a miRNA-specific stem-loop RT primer is used for RT, which is followed by TaqMan real-time PCR assay using specific forward primer in combination with universal reverse primer and TaqMan probe. The assay has shown high sensitivity (≤50 copies/reaction) for miRNA detection in two breast cancer cell lines, MCF-7 and MDA-MB-231. This assay might be implicated as a rapid and cost effective method for the detection of small non-coding RNAs.