The objective is to develop a system to automatically select the corresponding assessment scales and calculate the score of the risk based on the joint angle information obtained from the imaged ...process (OpenPose) via image-based motion capture technology. Current occupational assessments, for example, REBA, RULA, and OWAS were used to evaluate the risk of musculoskeletal disorders. However, the assessment result would not be reported immediately. Introducing real-time occupational assessments in different working environments will be helpful for occupational injury prevention. In this study, the decision tree was developed to select the most appropriate assessment method according to the joint angles derived by OpenPose image process. Fifteen operation videos were tested and these videos can be classified into six types including maintenance, handling, assembly, cleaning, office work, and driving. The selected ergonomic assessment method by our developed decision tree in each condition are consistent with the recommendation of the Labour Research Institute. Moreover, the high-risk posture could be identified immediately and provide to the inspector for further evaluation on this posture rather than the whole operation period. This approach provides a quick inspection of the operation movements to prevent musculoskeletal injuries and enhances the application of the scale assessment method in different industrial environments.
Crosstalk of a tumor with its microenvironment is a critical factor contributing to cancer development. This study investigates the soluble factors released by tumor-associated dendritic cells ...(TADCs) responsible for increasing cancer stem cell (CSC) properties, cell mobility, and epithelial-to-mesenchymal transition (EMT). Dendritic cells (DCs) of colon cancer patients were collected for phenotype and CXCL1 expression by flow cytometry and Luminex assays. The transcriptome of CXCL1-treated cancer cells was established by next generation sequencing. Inflammatory chemokine CXCL1, present in large amounts in DCs isolated from colon cancer patients, and SW620-conditioned TADCs, enhance CSC characteristics in cancer, supported by enhanced anchorage-independent growth, CD133 expression and aldehyde dehydrogenase activity. Additionally, CXCL1 increases the metastatic ability of a cancer by enhancing cell migration, matrix metalloproteinase-7 expression and EMT. The enhanced CXCL1 expression in DCs is also noted in mice transplanted with colon cancer cells. Transcriptome analysis of CXCL1-treated SW620 cells indicates that CXCL1 increases potential oncogene expression in colon cancer, including
,
,
,
and
. Concurrently, CXCL1 displays a specific microRNA (miR) upregulated by the prototypical colon cancer onco-miR miR-105. Analysis of publicly available data reveals CXCL1-driven oncogenes and miR-105 have a negative prognostic impact on the outcome of colon cancer. This study indicates a new mechanism by which the colon cancer milieu exploits DC plasticity to support cancer progression.
Background and Aim
Hepatitis B virus (HBV) may reactivate when treating chronic hepatitis C (CHC) with direct acting antivirals (DAA). We aim to investigate the risk of HBV reactivation during DAA ...therapy.
Methods
Chronic hepatitis C patients receiving pan‐oral DAA therapy from December 2013 to August 2016 were evaluated. Fifty‐seven patients that had a past HBV infection (negative hepatitis B surface antigen HBsAg and positive hepatitis B core antibody) and seven patients that had a current HBV infection (positive HBsAg) were enrolled. Serum HBV and hepatitis C virus (HCV) markers were regularly measured. The endpoints were the HCV sustained virological response (SVR) and the HBV virological/clinical reactivation.
Results
The overall SVR12 rate was 96.9%, and two patients, one with positive HBsAg, had a relapse of HCV. No episodes of HBV virological reactivation were observed among the patients with a past HBV infection. For the seven patients with a current HBV infection, HBV virological reactivation was found in four (57.1%) of the seven patients. Clinical reactivation of HBV was observed in one patient with pretreatment detectable HBV DNA and recovered after entecavir administration. For the other three patients with HBV virological reactivation, the reappearance of low level HBV DNA without clinical reactivation was observed. HBsAg levels demonstrated only small fluctuations in all the patients.
Conclusions
There was a minimal impact of hepatitis B core antibody seropositivity on HCV efficacy and safety. For CHC patients with current HBV infection, the risk of HBV reactivation was present, and monitoring the HBV DNA level during therapy is warranted.
Cancer patients with diabetes are at increased risk for cardiovascular diseases due to common risk factors and well-documented drug-associated cardiotoxicity. Sodium-glucose cotransporter-2 (SGLT2) ...inhibitors have shown cardiovascular benefits in patients with diabetes, but their effects on cancer patients remain unclear. This study aimed to evaluate the cardiovascular outcomes associated with SGLT2 inhibitor therapy in patients with concomitant diabetes and cancer.
We conducted a systematic review and meta-analysis of cohort studies comparing cardiovascular outcomes between cancer patients with diabetes receiving SGLT2 inhibitors and those not receiving SGLT2 inhibitors. PubMed, Embase, and the Cochrane Library were searched from inception to February 29, 2024. The primary outcome was all-cause mortality, and the secondary outcomes were heart failure hospitalization, and adverse events. Random-effect models were used to calculate pooled risk ratios (RR) with 95% confidence intervals (CI). Subgroup and sensitivity analyses were conducted to identify potential sources of heterogeneity and explore the effect of SGLT2 inhibitors on mitigating cardiotoxicity.
Nine cohort studies involving 82,654 patients were included. SGLT2 inhibitor use was associated with a significantly lower risk of all-cause mortality (RR 0.46, 95% CI 0.31-0.68, P < 0.0001; I
= 98%) and heart failure hospitalization (RR 0.49, 95% CI 0.30-0.81, P = 0.006; I
= 21%) compared to non-use. The mortality benefit remained significant in patients receiving anthracycline chemotherapy (RR 0.50, 95% CI 0.28-0.89, P = 0.02; I
= 71%). SGLT2 inhibitor use was also associated with a lower risk of sepsis (RR 0.32, 95% CI 0.23-0.44, P < 0.00001; I
= 0%) and no increased risk of diabetic ketoacidosis (RR 0.66, 95% CI 0.20-2.16, P = 0.49; I
= 0%).
SGLT2 inhibitor therapy is associated with lower risks of all-cause mortality and heart failure hospitalization in patients with concomitant diabetes and cancer. These findings suggest that SGLT2 inhibitors may offer cardiovascular benefits in this high-risk population. Randomized controlled trials are needed to validate these findings and evaluate the safety and efficacy of SGLT2 inhibitors in specific cancer types and treatment regimens.
Human ubiquinol-cytochrome c reductase core protein 1 (UQCRC1) is an evolutionarily conserved core subunit of mitochondrial respiratory chain complex III. We recently identified the ...disease-associated variants of UQCRC1 from patients with familial parkinsonism, but its function remains unclear. Here we investigate the endogenous function of UQCRC1 in the human neuronal cell line and the Drosophila nervous system. Flies with neuronal knockdown of uqcrc1 exhibit age-dependent parkinsonism-resembling defects, including dopaminergic neuron reduction and locomotor decline, and are ameliorated by UQCRC1 expression. Lethality of uqcrc1-KO is also rescued by neuronally expressing UQCRC1, but not the disease-causing variant, providing a platform to discern the pathogenicity of this mutation. Furthermore, UQCRC1 associates with the apoptosis trigger cytochrome c (cyt-c), and uqcrc1 deficiency increases cyt-c in the cytoplasmic fraction and activates the caspase cascade. Depleting cyt-c or expression of the anti-apoptotic p35 ameliorates uqcrc1-mediated neurodegeneration. Our findings identify a role for UQCRC1 in regulating cyt-c-induced apoptosis.
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•Neuronal reduction of uqcrc1, the ETC complex III subunit, causes PD-like symptoms•uqcrc1 regulates DA neuronal maintenance and locomotor activity in flies•The disease-associated uqcrc1 variant fails to bind cytochrome c, triggering apoptosis•Targeting cytochrome c, but not ROS, ameliorates uqcrc1-mediated neurodegeneration
Point mutations in human UQCRC1 associate with familial parkinsonism, but the underlying mechanisms remain unclear. Using the fruit fly as a model, Hung et al. show that the disease variant fails to retain apoptosis trigger cyt-c in mitochondria, resulting in apoptotic neurodegeneration.
Background
MicroRNA (miR)-184 has been reported to have a dual role in human cancers. However, the role of miR-184 in non-small cell lung cancer (NSCLC) remains unclear.
Methods
Wild-type or mutant ...CDC25A promoters were constructed by PCR and site-directed mutagenesis to verify whether miR-184 could inhibit CDC25A expression at post-transcription level. Boyden chamber assay was used to assess whether miR-184 could modulate cell invasiveness via targeting CDC25A and c-Myc. We utilized 124 tumors from NSCLC patients to determine miR-184, miR-21, PDCD4 mRNA, c-Myc mRNA, and CDC25A mRNA expression levels by means of real-time PCR analysis. The prognostic value of CDC25A, c-Myc, and miR-184 on overall survival (OS) and relapse-free survival (RFS) was evaluated by Kaplan–Meier and Cox regression analysis.
Results
MiR-184 suppressed CDC25A expression by enhancing the instability of its mRNA as a result of miR-184 binding to its coding region. An increase in CDC25A expression by means of a reduction in miR-184 promotes cell invasiveness. Moreover, a concomitant increase in CDC25A and c-Myc expression as a result of decreased miR-184 via the miR-21-mediated PDCD4 reduction is responsible for cell invasiveness. Among patients, miR-184 expression in lung tumors was found to correlate negatively with CDC25A mRNA, c-Myc mRNA, and miR-21 expression, but was positively related to PDCD4 mRNA expression. High-miR-184, High-CDC25A, or high-c-Myc mRNA tumors exhibited shorter OS and RFS periods than their counterparts. The worst OS and RFS were observed in low-miR-184/high-CDC25A/high-c-Myc tumors, followed by low-miR-184 /high-CDC25A, low-miR-184/high-c-Myc, high-c-Myc, and high-CDC25A tumors.
Conclusions
MiR-184 as a tumor suppressor miR inhibits cell proliferation and invasion capability via targeting CDC25A and c-Myc. Low miR-184 level may predict worse prognosis in NSCLC patients.
The features used in the separation of different objects are important for successful point cloud classification. Eigen-features from a covariance matrix of a point set with the sample mean are ...commonly used geometric features that can describe the local geometric characteristics of a point cloud and indicate whether the local geometry is linear, planar, or spherical. However, eigen-features calculated by the principal component analysis of a covariance matrix are sensitive to LiDAR data with inherent noise and incomplete shapes because of the non-robust statistical analysis. To obtain reliable eigen-features from LiDAR data and to improve classification accuracy, we introduce a method of analyzing local geometric characteristics of a point cloud by using a weighted covariance matrix with a geometric median. Each point is assigned a weight to represent its spatial contribution in the weighted principal component analysis and to estimate the geometric median which can be regarded as a localized center of a shape. In the experiments, qualitative and quantitative analyses on airborne LiDAR data and simulated point clouds show a clear improvement of the proposed method compared with the standard eigen-features. The classification accuracy is improved by 1.6–4.5% using a supervised classifier.
Aryl hydrocarbon receptor (AHR) genomic pathway has been well-characterized in a number of respiratory diseases. In addition, the cytoplasmic AHR protein may act as an adaptor of E3 ubiquitin ligase. ...In this study, the physiological functions of AHR that regulate cell proliferation were explored using the CRISPR/Cas9 system. The doubling-time of the AHR-KO clones of A549 and BEAS-2B was observed to be prolonged. The attenuation of proliferation potential was strongly associated with either the induction of p27
or the impairment in mitogenic signal transduction driven by the epidermal growth factor (EGF) and EGF receptor (EGFR). We found that the leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1), a repressor of EGFR, was induced in the absence of AHR in vitro and in vivo. The LRIG1 tends to degrade via a proteasome dependent manner by interacting with AHR in wild-type cells. Either LRIG1 or a disintegrin and metalloprotease 17 (ADAM17) were accumulated in AHR-defective cells, consequently accelerating the degradation of EGFR, and attenuating the response to mitogenic stimulation. We also affirmed low AHR but high LRIG1 levels in lung tissues of chronic obstructive pulmonary disease (COPD) patients. This might partially elucidate the sluggish tissue repairment and developing inflammation in COPD patients.
About one-third of patients with advanced renal cell carcinoma (RCC) have bone metastasis that are often osteolytic and cause substantial morbidity, such as pain, pathologic fracture, spinal cord ...compression and hypercalcemia. The presence of bone metastasis in RCC is also associated with poor prognosis. Bone-targeted treatment using bisphosphonate and denosumab can reduce skeletal complications in RCC, but does not cure the disease or improve survival. Elucidating the molecular mechanisms of tumor-induced changes in the bone microenvironment is needed to develop effective treatment. The "vicious cycle" hypothesis has been used to describe how tumor cells interact with the bone microenvironment to drive bone destruction and tumor growth. Tumor cells secrete factors like parathyroid hormone-related peptide, transforming growth factor-β and vascular endothelial growth factor, which stimulate osteoblasts and increase the production of the receptor activator of nuclear factor κB ligand (RANKL). In turn, the overexpression of RANKL leads to increased osteoclast formation, activation and survival, thereby enhancing bone resorption. This review presents a general survey on bone metastasis in RCC by natural history, interaction among the immune system, bone and tumor, molecular mechanisms, bone turnover markers, therapies and healthcare burden.
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