Oleanolic acid increases the anticancer potency of doxorubicin in pancreatic cancer cells

Combination therapy is a novel cancer therapy approach that combines two or more chemotherapy drugs. This treatment modality enhances the efficacy of chemotherapy by targeting key pathways in an additive or synergistic manner. Therefore, we investigated the efficacy of combination therapy by widely used chemotherapy drug doxorubicin (DOX) and oleanolic acid (OA) to induction of apoptosis for pancreatic cancer (PC) therapy. The effects of DOX, OA, and their combination (DOX-OA) were investigated on proliferation and viability of PC cell line (PANC-1) by MTT assay. Moreover, migration and invasion of the cancer cells were evaluated by trans-well migration assay and wound healing assay. Flow cytometry and DAPI (4′,6-diamidino-2-phenylindole) staining were employed to investigate apoptosis quantification and qualification of the treated cancer cells. Finally, mRNA expression of apoptosis-related genes was assessed by quantitative real-time polymerase chain reaction. Our results demonstrated that the proliferation and metastasis potential of PC cells significantly decreased after treatment by DOX, OA, and DOX-OA. Moreover, we observed an increase in apoptosis percentage in the treated cancer cells. The apoptosis-related gene expression was modified to increase the apoptosis rate in all of the treatment groups. However, the anticancer potency of DOX-OA combination was significantly more than that of DOX and OA treatments alone. Our study suggested that DOX-OA combination exerts more profound anticancer effects against PC cell lines than DOX or OA monotherapy. This approach may increase the efficiency of chemotherapy and reduce unintended side effects by lowering the prescribed dose of DOX.     

Finite element simulation of an artificial intervertebral disk using fiber reinforced laminated composite model

Degeneration of intervertebral disk (IVD) has been increased in recent years. The lumbar herniation can be cured using conservative and surgical procedures. Surgery is considered after failure of conservative treatment. Partial discectomy, fusion, and total disk replacement (TDR) are also common surgical treatments for degenerative disk disease. However, due to limitations and disadvantages of the current treatments, many studies have been carried out to approach the best design of mimicking natural disk. Recently, a new method of TDRs has been introduced using nature deformation of IVD by reinforced fibers of annulus fibrosis. Nonetheless, owing to limitations of experimental works on the human body, numerical studies of IVD may help to understand load transfer and biomechanical properties within the disks with reinforced fibers. In this study, a three-dimensional (3D) finite element model of the L2-L3 disk vertebrae unit with 12 vertical fibers embedded into annulus fibrosis was constructed. The IVD was subjected to compressive force, bending moment, and axial torsion. The most important parameters of disk failures were compared to that of experimental data. The results showed that the addition of reinforced fibers into the disk invokes a significant decrease of stress in the nucleus and annulus. The findings of this study may have implications not only for developing IVDs with reinforced fibers but also for the application of fiber reinforced IVD in orthopedics surgeries as a suitable implant.     

Perceived Quality of Informed Refusal Process: A Cross‐Sectional Study from Iranian Patients' Perspectives

Patients have the right to refuse their treatment; however, this refusal should be informed. We evaluated the quality of the informed refusal process in Iranian hospitals from patients' viewpoints. To this end, we developed a questionnaire that covered four key aspects of the informed refusal process including; information disclosure, voluntariness, comprehension, and provider‐patient relationship. A total of 284 patients who refused their treatment from 12 teaching hospitals in the Isfahan Province, Iran, were recruited and surveyed to produce a convenience sample. Patients' perceptions about the informed refusal process were scored and the mean scores of the four components were calculated. The findings showed that the practice of information disclosure (9.6 ± 6.4 out of 22 points) was perceived to be moderate, however, comprehension (2.3 ± 1.4 out of 4 points), voluntariness (8.7 ± 1.5 out of 12 points) and provider–patient relationship (10.2 ± 5.2 out of 16 points) were perceived to be relatively good. We found that patients, who refused their care before any treatment had commenced, reported a lower quality of information disclosure and voluntariness. Patients informed by nurses and those who had not had a previous related admission, reported lower scores for comprehension and relationship. In conclusion, the process of obtaining informed refusal was relatively satisfactory except for levels of information disclosure. To improve current practices, Iranian patients need to be better informed about; different treatment options, consequences of treatment refusal, costs of not continuing treatment and follow‐ups after refusal. Developing more informative refusal forms is needed.     

Classification of ECG arrhythmia by a modular neural network based on Mixture of Experts and Negatively Correlated Learning

In this paper, we propose a novel ECG arrhythmia classification method using the complementary features of Mixture of Experts (ME) and Negatively Correlated Learning (NCL). Negative Correlation Learning and Mixture of Experts methods utilize different error functions for simultaneous training of negatively correlated Neural Networks. The capability of a control parameter for NCL is incorporated in the error function of ME, which enables the training algorithm of ME to establish a balance in bias-variance-covariance trade-offs. ECG records from the MIT-BIH arrhythmia database are selected as test data. It is observed that the proposed classification method not only preserves the advantages and alleviates the disadvantages of its basis approaches, but also offering significantly improved performance over the original methods.     

Comparative analysis of fish environmental DNA reveals higher sensitivity achieved through targeted sequence-based metabarcoding

Environmental DNA (eDNA)-based methods of species detection are enabling various applications in ecology and conservation including large-scale biomonitoring efforts. qPCR is widely used as the standard approach for species-specific detection, often targeting a fish species of interest from aquatic eDNA. However, DNA metabarcoding has the potential to displace qPCR in certain eDNA applications. In this study, we compare the sensitivity of the latest Illumina NovaSeq 6000 NGS platform to qPCR TaqMan assays by measuring limits of detection and by analysing eDNA from water samples collected from Churchill River and Lake Melville, NL, Canada. Species-specific, targeted next generation sequencing (NGS) assays had significantly higher sensitivity than qPCR, with limits of detection 14- to 29-fold lower. For example, when analysing eDNA, qPCR detected Gadus ogac (Greenland cod) in 21% of samples, but targeted NGS detected this species in 29% of samples. General NGS assays were as sensitive as qPCR, while simultaneously detecting 15 fish species from eDNA samples. With over 34,000 fish species on the planet, parallel and sensitive methods such as NGS will be required to support effective biomonitoring at both regional and global scales.