Notes

Cardiorespiratory combining is owned by exercising capacity within patients with continual obstructive lung ailment.
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder that causes vascular malformations throughout the body. The most prevalent and accessible of these lesions are found throughout the skin and mucosa, and often rupture causing bleeding and anemia. A recent increase in potential HHT treatments have created a demand for quantitative metrics that can objectively measure the efficacy of new and developing treatments. We employ optical coherence tomography (OCT)-a high resolution, non-invasive imaging modality in a novel pipeline to image and quantitatively characterize dermal HHT lesion behavior over time or throughout the course of treatment. This study is aimed at detecting detailed morphological changes of dermal HHT lesions to understand the underlying dynamic processes of the disease. We present refined metrics tailored for HHT, developed from a pilot study using 3 HHT patients and 6 lesions over the course of multiple imaging dates, totalling to 26 lesion images. Preliminary results from these lesions are presented in this paper alongside representative OCT images. This study provides a new objective method to analyse and understand HHT lesions using a minimally invasive, accessible, cost-effective, and efficient imaging modality with quantitative metrics describing morphology and blood flow.Innate radioresistance substantially limits the effectiveness of radiotherapy for colorectal cancer (CRC); thus, a strategy to enhance the radiosensitivity of CRC is urgently needed. Herein, we reported that ankyrin repeat and KH domain containing 1 (ANKHD1) serves as a key regulator of radioresistance in CRC. ANKHD1 was highly expressed in CRC tissues and was highly correlated with Yes-associated protein 1 (YAP1) in CRC. Our results first revealed that ANKHD1 knockdown could increase the radiosensitivity of CRC by regulating DNA-damage repair, both in vitro and in vivo. Furthermore, the interactive regulation between ANKHD1 or YAP1 and lncRNA MALAT1 was revealed by RIP and RNA pull-down assays. Moreover, our results also demonstrated that MALAT1 silencing can radiosensitize CRC cells to IR through YAP1/AKT axis, similar to ANKHD1 silencing. Taken together, we report a feedback loop of ANKHD1/MALAT1/YAP1 that synergistically promotes the transcriptional coactivation of YAP1 and in turn enhances the radioresistance of CRC by regulating DNA-damage repair, probably via the YAP1/AKT axis. Our results suggested that targeting the YAP1/AKT axis downstream of ANKHD1/MALAT1/YAP1 may enhance the radiosensitivity of CRC.The role of hepatocellular carcinoma (HCC) surveillance is being questioned in alcoholic cirrhosis because of the relative low HCC risk. This study aimed to assess the risk and predictors of HCC in Korean patients with alcoholic cirrhosis by using competing risk analysis. A total of 745 patients with alcoholic cirrhosis were recruited at a university-affiliated hospital in Korea and randomly assigned to either the derivation (n = 507) and validation (n = 238) cohort. Subdistribution hazards model of Fine and Gray was used with deaths and liver transplantation treated as competing risks. Death records were confirmed from Korean government databases. A nomogram was developed to calculate the Alcohol-associated Liver Cancer Estimation (ALICE) score. The cumulative incidence of HCC was 15.3 and 13.3% at 10 years for derivation and validation cohort, respectively. Age, alpha-fetoprotein level, and albumin level were identified as independent predictors of HCC and incorporated in the ALICE score, which discriminated low, intermediate, and high risk for HCC in alcoholic cirrhosis at the cut-off of 60 and 100. The risk of HCC can be stratified by using a combination of readily available clinical parameters (age, AFP level, and albumin level) in patients with alcoholic cirrhosis.Fiber-reinforced ceramic-matrix composites are advanced, temperature resistant materials with applications in aerospace engineering. Their analysis involves the detection and separation of fibers, embedded in a fiber bed, from an imaged sample. Currently, this is mostly done using semi-supervised techniques. Here, we present an open, automated computational pipeline to detect fibers from a tomographically reconstructed X-ray volume. We apply our pipeline to a non-trivial dataset by Larson et al. To separate the fibers in these samples, we tested four different architectures of convolutional neural networks. When comparing our neural network approach to a semi-supervised one, we obtained Dice and Matthews coefficients reaching up to 98%, showing that these automated approaches can match human-supervised methods, in some cases separating fibers that human-curated algorithms could not find. The software written for this project is open source, released under a permissive license, and can be freely adapted and re-used in other domains.Hepatocellular carcinoma (HCC) is one of the leading lethal malignancies and a hypervascular tumor. Although some long non-coding RNAs (lncRNAs) have been revealed to be involved in HCC. The contributions of lncRNAs to HCC progression and angiogenesis are still largely unknown. In this study, we identified a HCC-related lncRNA, CMB9-22P13.1, which was highly expressed and correlated with advanced stage, vascular invasion, and poor survival in HCC. We named this lncRNA Progression and Angiogenesis Associated RNA in HCC (PAARH). Gain- and loss-of function assays revealed that PAARH facilitated HCC cellular growth, migration, and invasion, repressed HCC cellular apoptosis, and promoted HCC tumor growth and angiogenesis in vivo. PAARH functioned as a competing endogenous RNA to upregulate HOTTIP via sponging miR-6760-5p, miR-6512-3p, miR-1298-5p, miR-6720-5p, miR-4516, and miR-6782-5p. The expression of PAARH was significantly positively associated with HOTTIP in HCC tissues. Functional rescue assays verified that HOTTIP was a critical mediator of the roles of PAARH in modulating HCC cellular growth, apoptosis, migration, and invasion. Furthermore, PAARH was found to physically bind hypoxia inducible factor-1 subunit alpha (HIF-1α), facilitate the recruitment of HIF-1α to VEGF promoter, and activate VEGF expression under hypoxia, which was responsible for the roles of PAARH in promoting angiogenesis. The expression of PAARH was positively associated with VEGF expression and microvessel density in HCC tissues. In conclusion, these findings demonstrated that PAARH promoted HCC progression and angiogenesis via upregulating HOTTIP and activating HIF-1α/VEGF signaling. PAARH represents a potential prognostic biomarker and therapeutic target for HCC.Metastases are initiated by disseminated tumor cells (DTCs) that colonize distant organs. Growing evidence suggests that the microenvironment of the primary tumor primes DTCs for dormant or proliferative fates. However, the manner in which this occurs remains poorly understood. Here, using the Window for High-Resolution Intravital Imaging of the Lung (WHRIL), we study the live lung longitudinally and follow the fate of individual DTCs that spontaneously disseminate from orthotopic breast tumors. We find that spontaneously DTCs have increased levels of retention, increased speed of extravasation, and greater survival after extravasation, compared to experimentally metastasized tumor cells. Detailed analysis reveals that a subset of macrophages within the primary tumor induces a pro-dissemination and pro-dormancy DTC phenotype. Our work provides insight into how specific primary tumor microenvironments prime a subpopulation of cells for expression of proteins associated with dissemination and dormancy.Estimated genetic associations with prognosis, or conditional on a phenotype (e.g. disease incidence), may be affected by collider bias, whereby conditioning on the phenotype induces associations between causes of the phenotype and prognosis. We propose a method, 'Slope-Hunter', that uses model-based clustering to identify and utilise the class of variants only affecting the phenotype to estimate the adjustment factor, assuming this class explains more variation in the phenotype than any other variant classes. Simulation studies show that our approach eliminates the bias and outperforms alternatives even in the presence of genetic correlation. In a study of fasting blood insulin levels (FI) conditional on body mass index, we eliminate paradoxical associations of the underweight loci COBLLI; PPARG with increased FI, and reveal an association for the locus rs1421085 (FTO). In an analysis of a case-only study for breast cancer mortality, a single region remains associated with more pronounced results.Obesity and ethnicity are known risk factors for COVID-19 outcomes, but their combination has not been extensively examined. We investigate the association between body mass index (BMI) and COVID-19 mortality across different ethnic groups using linked national Census, electronic health records and mortality data for adults in England from the start of pandemic (January 2020) to December 2020. There were 30,067 (0.27%), 1,208 (0.29%), 1,831 (0.29%), 845 (0.18%) COVID-19 deaths in white, Black, South Asian and other ethnic minority groups, respectively. Here we show that BMI was more strongly associated with COVID-19 mortality in ethnic minority groups, resulting in an ethnic risk of COVID-19 mortality that was dependant on BMI. The estimated risk of COVID-19 mortality at a BMI of 40 kg/m2 in white ethnicities was equivalent to the risk observed at a BMI of 30.1 kg/m2, 27.0 kg/m2, and 32.2 kg/m2 in Black, South Asian and other ethnic minority groups, respectively.Transketolase (TKT) which is an important metabolic enzyme in the pentose phosphate pathway (PPP) participates in maintaining ribose 5-phosphate levels. TKT is necessary for maintaining cell growth. However, we found that in addition to this, TKT can also affect tumor progression through other ways. Our previous study indicate that TKT could promote the development of liver cancer by affecting bile acid metabolism. And in this study, we discovered that TKT expression was remarkably upregulated in colorectal cancer, abnormal high expression of TKT is associated with poor prognosis of colorectal cancer. Additionally, TKT promoted colorectal cancer cell growth and metastasis. Further study demonstrated that TKT interacted with GRP78 and promoted colorectal cancer cell glycolysis through increasing AKT phosphorylation, thereby enhancing colorectal cancer cell metastasis. Thus, TKT is expected to become an indicator for judging the prognosis of colorectal cancer, and provide a theoretical basis for drug development of new treatment targets for colorectal cancer.Breast cancer is the most common malignancy among women across the globe. Recent studies have revealed that many long non-coding RNAs (lncRNAs) regulate the Wnt/β-catenin signaling pathway in several types of cancer. Hyperactivation of the Wnt/β-catenin pathway has been extensively presented in breast cancer and is involved in breast cancer progression. However, the underlying molecular mechanism remains elusive. In the current study, we found lncRNA RBM5-AS1 was remarkably upregulated in breast cancer cells and tissues. Overexpression of RBM5-AS1 facilitated proliferation, migration, invasion, EMT, and stemness maintenance of breast cancer cells in vitro and in vivo. Mechanism studies suggested that RBM5-AS1 could be transcriptionally activated by hypoxia-induced RUNX2. Upregulated RBM5-AS1 further activated the Wnt/β-catenin signaling by preventing β-catenin degradation and by helping organize β-catenin-TCF4 transcriptional complex. These findings suggested that RBM5-AS1, a regulator of Wnt/β-catenin signaling, plays a vital role in breast cancer initiation and progression, implicating its potential as a new target for breast cancer treatment.
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