Inhibitory effects of megakaryocytic cells in prostate cancer skeletal metastasis

Prostate cancer cells commonly spread through the circulation, but few successfully generate metastatic foci in bone. Osteoclastic cellular activity has been proposed as an initiating event for skeletal metastasis. Megakaryocytes (MKs) inhibit osteoclastogenesis, which could have an impact on tumor establishment in bone. Given the location of mature MKs at vascular sinusoids, they may be the first cells to physically encounter cancer cells as they enter the bone marrow. Identification of the interaction between MKs and prostate cancer cells was the focus of this study. K562 (human MK precursors) and primary MKs derived from mouse bone marrow hematopoietic precursor cells potently suppressed prostate carcinoma PC-3 cells in coculture. The inhibitory effects were specific to prostate carcinoma cells and were enhanced by direct cell-cell contact. Flow cytometry for propidium iodide (PI) and annexin V supported a proapoptotic role for K562 cells in limiting PC-3 cells. Gene expression analysis revealed reduced mRNA levels for cyclin D1, whereas mRNA levels of apoptosis-associated specklike protein containing a CARD (ASC) and death-associated protein kinase 1 (DAPK1) were increased in PC-3 cells after coculture with K562 cells. Recombinant thrombopoietin (TPO) was used to expand MKs in the marrow and resulted in decreased skeletal lesion development after intracardiac tumor inoculation. These novel findings suggest a potent inhibitory role of MKs in prostate carcinoma cell growth in vitro and in vivo. This new finding, of an interaction of metastatic tumors and hematopoietic cells during tumor colonization in bone, ultimately will lead to improved therapeutic interventions for prostate cancer patients. © 2011 American Society for Bone and Mineral Research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78486/1/204_ftp.pd

Osteoarthritis of the Temporomandibular Joint can be diagnosed earlier using biomarkers and machine learning

After chronic low back pain, Temporomandibular Joint (TMJ) disorders are the second most common musculoskeletal condition affecting 5 to 12% of the population, with an annual health cost estimated at $4 billion. Chronic disability in TMJ osteoarthritis (OA) increases with aging, and the main goal is to diagnosis before morphological degeneration occurs. Here, we address this challenge using advanced data science to capture, process and analyze 52 clinical, biological and high-resolution CBCT (radiomics) markers from TMJ OA patients and controls. We tested the diagnostic performance of four machine learning models: Logistic Regression, Random Forest, LightGBM, XGBoost. Headaches, Range of mouth opening without pain, Energy, Haralick Correlation, Entropy and interactions of TGF-β1 in Saliva and Headaches, VE-cadherin in Serum and Angiogenin in Saliva, VE-cadherin in Saliva and Headaches, PA1 in Saliva and Headaches, PA1 in Saliva and Range of mouth opening without pain; Gender and Muscle Soreness; Short Run Low Grey Level Emphasis and Headaches, Inverse Difference Moment and Trabecular Separation accurately diagnose early stages of this clinical condition. Our results show the XGBoost + LightGBM model with these features and interactions achieves the accuracy of 0.823, AUC 0.870, and F1-score 0.823 to diagnose the TMJ OA status. Thus, we expect to boost future studies into osteoarthritis patient-specific therapeutic interventions, and thereby improve the health of articular joints

High-pressure xenon gas time projection chamber with scalable design and its performance at around the Q value of 136^{136}Xe double-beta decay

We have been developing a high-pressure xenon gas time projection chamber (TPC) to search for neutrinoless double beta ($0\nu\beta\beta$) decay of $^{136}$Xe. The unique feature of this TPC is in the detection part of ionization electrons, called ELCC. ELCC is composed of multiple units, and one unit covers 48.5 $\mathrm{cm}^2$. A 180 L size prototype detector with 12 units, 672 channels, of ELCC was constructed and operated with 7.6 bar natural xenon gas to evaluate the performance of the detector at around the Q value of $^{136}$Xe $0\nu\beta\beta$. The obtained FWHM energy resolution is (0.73 $\pm$ 0.11) % at 1836 keV. This corresponds to (0.60 $\pm$ 0.03) % to (0.70 $\pm$ 0.21) % of energy resolution at the Q value of $^{136}Xe$ $0\nu\beta\beta$. This result shows the scalability of the AXEL detector with ELCC while maintaining high energy resolution. Factors determining the energy resolution were quantitatively evaluated and the result indicates further improvement is feasible. Reconstructed track images show distinctive structures at the endpoint of electron tracks, which will be an important feature to distinguish $0\nu\beta\beta$ signals from gamma-ray backgrounds.Comment: 33 pages, 24 figures, preprint accepted by PTE

Superhydrophobic Surface Based on a Coral-Like Hierarchical Structure of ZnO

Background: Fabrication of superhydrophobic surfaces has attracted much interest in the past decade. The fabrication methods that have been studied are chemical vapour deposition, the sol-gel method, etching technique, electrochemical deposition, the layer-by-layer deposition, and so on. Simple and inexpensive methods for manufacturing environmentally stable superhydrophobic surfaces have also been proposed lately. However, work referring to the influence of special structures on the wettability, such as hierarchical ZnO nanostructures, is rare. Methodology: This study presents a simple and reproducible method to fabricate a superhydrophobic surface with microscale roughness based on zinc oxide (ZnO) hierarchical structure, which is grown by the hydrothermal method with an alkaline aqueous solution. Coral-like structures of ZnO were fabricated on a glass substrate with a micro-scale roughness, while the antennas of the coral formed the nano-scale roughness. The fresh ZnO films exhibited excellent superhydrophilicity (the apparent contact angle for water droplet was about 0u), while the ability to be wet could be changed to superhydrophobicity after spin-coating Teflon (the apparent contact angle greater than 168u). The procedure reported here can be applied to substrates consisting of other materials and having various shapes. Results: The new process is convenient and environmentally friendly compared to conventional methods. Furthermore, the hierarchical structure generates the extraordinary solid/gas/liquid three-phase contact interface, which is the essentia

Automatic multi-anatomical skull structure segmentation of cone-beam computed tomography scans using 3D UNETR

The segmentation of medical and dental images is a fundamental step in automated clinical decision support systems. It supports the entire clinical workflow from diagnosis, therapy planning, intervention, and follow-up. In this paper, we propose a novel tool to accurately process a full-face segmentation in about 5 minutes that would otherwise require an average of 7h of manual work by experienced clinicians. This work focuses on the integration of the state-of-the-art UNEt TRansformers (UNETR) of the Medical Open Network for Artificial Intelligence (MONAI) framework. We trained and tested our models using 618 de-identified Cone-Beam Computed Tomography (CBCT) volumetric images of the head acquired with several parameters from different centers for a generalized clinical application. Our results on a 5-fold cross-validation showed high accuracy and robustness with a Dice score up to 0.962±0.02. Our code is available on our public GitHub repository

/STRU^NI RAD UDK 616.33-005.1-02:615.212.06

Terapija manifestnog krvavljenja iz gornjeg dela digestivnog trakta uzrokovanog uzimanjem nesteroidnih antiinflamatornih lekova (NSAIL

Polarization of Prostate Cancer-associated Macrophages Is Induced by Milk Fat Globule-EGF Factor 8 (MFG-E8)-mediated Efferocytosis*

Tumor cells secrete factors that modulate macrophage activation and polarization into M2 type tumor-associated macrophages, which promote tumor growth, progression, and metastasis. The mechanisms that mediate this polarization are not clear. Macrophages are phagocytic cells that participate in the clearance of apoptotic cells, a process known as efferocytosis. Milk fat globule- EGF factor 8 (MFG-E8) is a bridge protein that facilitates efferocytosis and is associated with suppression of proinflammatory responses. This study investigated the hypothesis that MFG-E8-mediated efferocytosis promotes M2 polarization. Tissue and serum exosomes from prostate cancer patients presented higher levels of MFG-E8 compared with controls, a novel finding in human prostate cancer. Coculture of macrophages with apoptotic cancer cells increased efferocytosis, elevated MFG-E8 protein expression levels, and induced macrophage polarization into an alternatively activated M2 phenotype. Administration of antibody against MFG-E8 significantly attenuated the increase in M2 polarization. Inhibition of STAT3 phosphorylation using the inhibitor Stattic decreased efferocytosis and M2 macrophage polarization in vitro, with a correlating increase in SOCS3 protein expression. Moreover, MFG-E8 knockdown tumor cells cultured with wild-type or MFG-E8-deficient macrophages resulted in increased SOCS3 expression with decreased STAT3 activation. This suggests that SOCS3 and phospho-STAT3 act in an inversely dependent manner when stimulated by MFG-E8 and efferocytosis. These results uncover a unique role of efferocytosis via MFG-E8 as a mechanism for macrophage polarization into tumor-promoting M2 cells