The landscape of exosomal non-coding RNAs in breast cancer drug resistance, focusing on underlying molecular mechanisms

Breast cancer (BC) is the most common malignancy among women worldwide. Like many other cancers, BC therapy is challenging and sometimes frustrating. In spite of the various therapeutic modalities applied to treat the cancer, drug resistance, also known as, chemoresistance, is very common in almost all BCs. Undesirably, a breast tumor might be resistant to different curative approaches (e.g., chemo- and immunotherapy) at the same period of time. Exosomes, as double membrane-bound extracellular vesicles 1) secreted from different cell species, can considerably transfer cell products and components through the bloodstream. In this context, non-coding RNAs (ncRNAs), including miRNAs, long ncRNAs (lncRNAs), and circular RNAs (circRNAs), are a chief group of exosomal constituents with amazing abilities to regulate the underlying pathogenic mechanisms of BC, such as cell proliferation, angiogenesis, invasion, metastasis, migration, and particularly drug resistance. Thereby, exosomal ncRNAs can be considered potential mediators of BC progression and drug resistance. Moreover, as the corresponding exosomal ncRNAs circulate in the bloodstream and are found in different body fluids, they can serve as foremost prognostic/diagnostic biomarkers. The current study aims to comprehensively review the most recent findings on BC-related molecular mechanisms and signaling pathways affected by exosomal miRNAs, lncRNAs, and circRNAs, with a focus on drug resistance. Also, the potential of the same exosomal ncRNAs in the diagnosis and prognosis of BC will be discussed in detail

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

GPR measurements to detect major discontinuities at Cheshmeh-Shirdoosh limestone quarry, Iran

In recent years, the Iranian rich quarry industry has been looking for efficient scientific investigations to improve the extraction operations in different dimension stone quarries. Kerman Province is one of the most potential zones with a variety of dimension stone quarries near the city of Kerman. In this research, GPR measurements were carried out to detect major discontinuities at Cheshmeh-Shirdoosh limestone quarry, northeast of Kerman city. This quarry is being extracted by the diamond wire sawing method. As the first GPR study in Iranian quarries, a total length of about 1200 m was surveyed with 50 MHz and 250 MHz GPR antennas collecting data on the surface of the three extraction benches of the quarry. A 800 MHz antenna was also used to map the main defects of a block, which was extracted from a fractured section of the quarry. Six parallel profiles at 10 cm intervals were measured along one side of the block. The results obtained from the 250 MHz dataset were very encouraging and could detect all the major discontinuities. Interpreted profiles were also used to prepare depth slices of the density of joints for two main survey areas. As expected, GPR sections obtained from the 50 MHz antenna had a lower resolution but could clearly detect fault zones. The 800 MHz antenna could map the main defects of the extracted block. However, a higher frequency antenna (e.g., 2GHz or more) is recommended for mapping thin fractures

GPR measurements to detect major discontinuities at Cheshmeh-Shirdoosh limestone quarry, Iran

In recent years, the Iranian rich quarry industry has been looking for efficient scientific investigations to improve the extraction operations in different dimension stone quarries. Kerman Province is one of the most potential zones with a variety of dimension stone quarries near the city of Kerman. In this research, GPR measurements were carried out to detect major discontinuities at Cheshmeh-Shirdoosh limestone quarry, northeast of Kerman city. This quarry is being extracted by the diamond wire sawing method. As the first GPR study in Iranian quarries, a total length of about 1200 m was surveyed with 50 MHz and 250 MHz GPR antennas collecting data on the surface of the three extraction benches of the quarry. A 800 MHz antenna was also used to map the main defects of a block, which was extracted from a fractured section of the quarry. Six parallel profiles at 10 cm intervals were measured along one side of the block. The results obtained from the 250 MHz dataset were very encouraging and could detect all the major discontinuities. Interpreted profiles were also used to prepare depth slices of the density of joints for two main survey areas. As expected, GPR sections obtained from the 50 MHz antenna had a lower resolution but could clearly detect fault zones. The 800 MHz antenna could map the main defects of the extracted block. However, a higher frequency antenna (e.g., 2GHz or more) is recommended for mapping thin fractures

Virtual Reality Games for Rehabilitation of Upper Extremities in Stroke Patients

Introduction Stroke is one of the main causes of physical disability in which doing frequent and early exercise is imperative for rehabilitation. Virtual reality gaming has a high potential in rehabilitation leading to increased performance of patients. This study aimed to develop, validate and examine virtual reality games in chronic stroke patients. Methods This was a single before-after study. To determine the movements and content of games, 9 physiotherapists and 11 game designers were asked to participate in a questionnaire-based survey. Then, to evaluate the impact of games on rehabilitation, patients (N = 10; mean age = 52 ± 4.38) with chronic stroke were asked to play the games three times a week for four weeks. Outcomes included measurement of the ability to perform shoulder, elbow and wrist movements was performed using goniometric instrument, Modified Motor Assessment Scale (MMAS) was used to assess the functional ability of patients and muscle spasticity, and brunnstrom’s stages of recovery test was also used to assess spastic and involuntary muscle movement Results Games have positive effects on the horizontal abduction of shoulder (16.26±23.94, P= 0.02), horizontal adduction of shoulder (59.24±74.76, P= 0.00), supination of wrist (10.68±53.52, P = 0.02), elbow flexion (0.1±1.5, P= 0.00), and wrist flexion (0.06±1.34, P = 0.03). However, they had no effects on the flexion of shoulder, flexion of elbow, extension of elbow, and extension of wrist (p-value> 0.05). Conclusions The results showed that games improve the range of motion of the participants in terms of horizontal abduction and abduction of the shoulder, elbow flexion, and supination and flexion of the wrist. Due to the small sample size in this study, we recommend more studies with larger samples and a control group

Termination of Repeat Testing in Chemical Laboratories Based on Practice Guidelines: Examining the Effect of Rule-Based Repeat Testing in a Transplantation Center

Background. Although the automation of instruments has reduced the variability of results and errors of analysis, in some laboratories, repeating a test to confirm its accuracy is still performed for critical and noncritical results. However, the importance of repeat testing is not well established yet, and there are no clear criteria for repeating a test. Materials and Methods. In this cross-sectional study, all repeated tests for 26 biochemical analytes (i.e., albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), amylase, aspartate aminotransferase (AST), bilirubin total (BT), bilirubin direct (BD), blood urea nitrogen (BUN), calcium, chloride (Cl), cholesterol total (CholT), creatine kinase (CK), creatinine (Cr), glucose, gamma-glutamyl transferase (GGT), high-density lipoprotein-cholesterol (HDL-c), iron, lactate dehydrogenase (LDH), LDL-c, lipase, magnesium (Mg), phosphorus (Ph), protein total (ProtT), total iron binding capacity (TIBC), triglyceride (TG), and uric acid) were assessed in both critical and noncritical ranges over two consecutive months (routine subjective test repeats in the first month and rule-based repeats in the second month). To determine the usefulness of test repeats, differences between the initial and verified results were compared with the allowable bias, and repeat testing was considered necessary if it exceeded the allowable bias range. All causes of repeat testing, including linearity flags, delta checks, clinically significant values, and critical values, were also documented. All data, including the cause of repeats, initial and verified results, time, and costs in the two consecutive months, were transferred to Microsoft Excel for analysis. For comparison of data between the months, Student’s t-test was used. Results. A total of 7714 repeat tests were performed over two consecutive months. Although a significant decline (38%) was found in repeated tests in the second month (P < 0.001), there was no significant change in the percentage of unnecessary repeats (77% in the first month and 74% in the second month). In both consecutive months, AST and ALT were the most commonly repeated tests, and delta check was the most common cause of repeat testing. Mg, ALP, AST, and lipase showed the highest rates of necessary repeats, respectively (the least stable tests), while albumin, LDL, and CholT tests showed the highest rates of unnecessary repeats, respectively (the most stable tests). The total cost and delay in turnaround time (TAT) due to repeated testing decreased by 32% and 36%, respectively. Conclusion. Although repeat testing has been shown to be unnecessary in most cases, having a strict policy for repeat testing appears to be more valuable than avoiding it completely. Each laboratory is advised to establish its own protocol for repeat testing based on its own practice

Evaluation of the Expression Levels of miR-21-5p and miR-429 Genes in Biopsy Samples from Patients with Oral Squamous Cell Carcinoma

Introduction: MicroRNAs (miRs) are a group of endogenous, non-coding, 18-24 nucleotide length single-strand RNAs that mediate gene expression at the post-transcriptional level through mRNA degradation or translational repression. They are involved in regulating diverse cellular biological processes such as cell cycle, differentiation, and apoptosis. The deregulation of miRs affects normal biological processes, leading to malignancies, including oral squamous cell carcinoma (OSCC). This study evaluates the expression level of miR-21-5p and miR-429 genes in biopsy samples from patients with OSCC and performs a comparison with controls. Materials and Methods: In this study, tissue samples were obtained from 40 individuals (20 OSCC patients and 20 healthy controls) to determine miR-21-5p and miR-429 expression using the ΔCT method and analyzed by the Mann–Whitney test. Results: The mean age of subjects in the control and patient groups was 47.15 and 53.8 years, respectively. According to the Mann–Whitney test, significant differences were observed in miR-21-5p (p p = 0.0191) expression levels between the two groups (p < 0.05). Conclusions: The expression of miR-21-5p, miR-429, and combined miRNAs in the OSCC group was significantly higher compared to the control group. As a result, changes in the expression of these biomarkers in cancerous tissues could potentially be considered as a marker for the early diagnosis of OSCC