88 research outputs found

    Accuracy of Pedicle Screw Placement in Scoliosis Surgery: A Comparison between Conventional Computed Tomography-Based and O-Arm-Based Navigation Techniques

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    Study DesignRetrospective study.PurposeWe compared the accuracy of O-arm-based navigation with computed tomography (CT)-based navigation in scoliotic surgery.Overview of LiteratureNo previous reports comparing the results of O-arm-based navigation with conventional CT-based navigation in scoliotic surgery have been published.MethodsA total of 222 pedicle screws were implanted in 29 patients using CT-based navigation (group C) and 416 screws were implanted in 32 patients using O-arm-based navigation (group O). Postoperative CT was performed to assess the screw accuracy, using the established Neo classification (grade 0: no perforation, grade 1: perforation <2 mm, grade 2: perforation ≥2 and <4, and grade 3: perforation ≥4 mm).ResultsIn group C, 188 (84.7%) of the 222 pedicle screw placements were categorized as grade 0, 23 (10.4%) were grade 1, 11 (5.0%) were grade 2, and 0 were grade 3. In group O, 351 (84.4%) of the 416 pedicle screw placements were categorized as grade 0, 52 (12.5%) were grade 1, 13 (3.1%) were grade 2, and 0 were grade 3. Statistical analysis showed no significant difference in the prevalence of grade 2.3 perforations between groups C and O. The time to position one screw, including registration, was 10.9±3.2 minutes in group C, but was significantly decreased to 5.4±1.1 minutes in group O.ConclusionsO-arm-based navigation facilitates pedicle screw insertion as accurately as conventional CT-based navigation. The use of O-arm-based navigation successfully reduced the time, demonstrating advantages in the safety and accuracy of pedicle screw placement for scoliotic surgery

    Tumor innate immunity primed by specific interferon-stimulated endogenous retroviruses.

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    Mesenchymal tumor subpopulations secrete pro-tumorigenic cytokines and promote treatment resistance1-4. This phenomenon has been implicated in chemorefractory small cell lung cancer and resistance to targeted therapies5-8, but remains incompletely defined. Here, we identify a subclass of endogenous retroviruses (ERVs) that engages innate immune signaling in these cells. Stimulated 3 prime antisense retroviral coding sequences (SPARCS) are oriented inversely in 3' untranslated regions of specific genes enriched for regulation by STAT1 and EZH2. Derepression of these loci results in double-stranded RNA generation following IFN-γ exposure due to bi-directional transcription from the STAT1-activated gene promoter and the 5' long terminal repeat of the antisense ERV. Engagement of MAVS and STING activates downstream TBK1, IRF3, and STAT1 signaling, sustaining a positive feedback loop. SPARCS induction in human tumors is tightly associated with major histocompatibility complex class 1 expression, mesenchymal markers, and downregulation of chromatin modifying enzymes, including EZH2. Analysis of cell lines with high inducible SPARCS expression reveals strong association with an AXL/MET-positive mesenchymal cell state. While SPARCS-high tumors are immune infiltrated, they also exhibit multiple features of an immune-suppressed microenviroment. Together, these data unveil a subclass of ERVs whose derepression triggers pathologic innate immune signaling in cancer, with important implications for cancer immunotherapy

    EMPRESS. IX. Extremely Metal-Poor Galaxies are Very Gas-Rich Dispersion-Dominated Systems: Will JWST Witness Gaseous Turbulent High-z Primordial Galaxies?

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    We present kinematics of 6 local extremely metal-poor galaxies (EMPGs) with low metallicities (0.0160.098 Z0.016-0.098\ Z_{\odot}) and low stellar masses (104.7107.6M10^{4.7}-10^{7.6} M_{\odot}). Taking deep medium-high resolution (R7500R\sim7500) integral-field spectra with 8.2-m Subaru, we resolve the small inner velocity gradients and dispersions of the EMPGs with Hα\alpha emission. Carefully masking out sub-structures originated by inflow and/or outflow, we fit 3-dimensional disk models to the observed Hα\alpha flux, velocity, and velocity-dispersion maps. All the EMPGs show rotational velocities (vrotv_{\rm rot}) of 5--23 km s1^{-1} smaller than the velocity dispersions (σ0\sigma_{0}) of 17--31 km s1^{-1}, indicating dispersion-dominated (vrot/σ0=0.290.80<1v_{\rm rot}/\sigma_{0}=0.29-0.80<1) systems affected by inflow and/or outflow. Except for two EMPGs with large uncertainties, we find that the EMPGs have very large gas-mass fractions of fgas0.91.0f_{\rm gas}\simeq 0.9-1.0. Comparing our results with other Hα\alpha kinematics studies, we find that vrot/σ0v_{\rm rot}/\sigma_{0} decreases and fgasf_{\rm gas} increases with decreasing metallicity, decreasing stellar mass, and increasing specific star-formation rate. We also find that simulated high-zz (z7z\sim 7) forming galaxies have gas fractions and dynamics similar to the observed EMPGs. Our EMPG observations and the simulations suggest that primordial galaxies are gas-rich dispersion-dominated systems, which would be identified by the forthcoming James Webb Space Telescope (JWST) observations at z7z\sim 7.Comment: Submitted to ApJ; After revisio

    \u3cem\u3eLkb1\u3c/em\u3e Inactivation Drives Lung Cancer Lineage Switching Governed by Polycomb Repressive Complex 2

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    Adenosquamous lung tumours, which are extremely poor prognosis, may result from cellular plasticity. Here, we demonstrate lineage switching of KRAS+ lung adenocarcinomas (ADC) to squamous cell carcinoma (SCC) through deletion of Lkb1 (Stk11) in autochthonous and transplant models. Chromatin analysis reveals loss of H3K27me3 and gain of H3K27ac and H3K4me3 at squamous lineage genes, including Sox2, ΔNp63 and Ngfr. SCC lesions have higher levels of the H3K27 methyltransferase EZH2 than the ADC lesions, but there is a clear lack of the essential Polycomb Repressive Complex 2 (PRC2) subunit EED in the SCC lesions. The pattern of high EZH2, but low H3K27me3 mark, is also prevalent in human lung SCC and SCC regions within ADSCC tumours. Using FACS-isolated populations, we demonstrate that bronchioalveolar stem cells and club cells are the likely cells-of-origin for SCC transitioned tumours. These findings shed light on the epigenetics and cellular origins of lineage-specific lung tumours
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