Genetic evidence supports the development of SLC26A9 targeting therapies for the treatment of lung disease

Over 400 variants in the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) are CF-causing. CFTR modulators target variants to improve lung function, but marked variability in response exists and current therapies do not address all CF-causing variants highlighting unmet needs. Alternative epithelial ion channel/transporters such as SLC26A9 could compensate for CFTR dysfunction, providing therapeutic targets that may benefit all individuals with CF. We investigate the relationship between rs7512462, a marker of SLC26A9 activity, and lung function pre- and post-treatment with CFTR modulators in Canadian and US CF cohorts, in the general population, and in those with chronic obstructive pulmonary disease (COPD). Rs7512462 CC genotype is associated with greater lung function in CF individuals with minimal function variants (for which there are currently no approved therapies; p = 0.008); and for gating (p = 0.033) and p.Phe508del/ p.Phe508del (p = 0.006) genotypes upon treatment with CFTR modulators. In parallel, human nasal epithelia with CC and p.Phe508del/p.Phe508del after Ussing chamber analysis of a combination of approved and experimental modulator treatments show greater CFTR function (p = 0.0022). Beyond CF, rs7512462 is associated with peak expiratory flow in a meta-analysis of the UK Biobank and Spirometa Consortium (p = 2.74 × 10−44) and provides p = 0.0891 in an analysis of COPD case-control status in the UK Biobank defined by spirometry. These findings support SLC26A9 as a therapeutic target to improve lung function for all people with CF and in individuals with other obstructive lung diseases

Ultra-Wideband Vertically Polarized Long-Slot Circular Phased Array

An ultra-wideband (UWB) vertically-polarized (VP) long-slot circular phased array with compact size is presented. The design realizes a quasi-magnetic current sheet array. It consists of just one circular array instead of a typical cylindrical system, which employs multiple circular arrays to achieve radiated fields with the same properties. A 16-element array was fabricated and measured to demonstrate its azimuthally invariant radiating capabilities. Measurement results show that the developed array achieves a wider impedance bandwidth, commendable cross-polarization discrimination (XPD), and a significantly more compact design than previously reported systems. In its omnidirectional mode, the array exhibits a 107.07% bandwidth (VSWR ≤ 2.0) with an XPD level better than 19.5 dB. In its directional mode, the array operates over 100% bandwidth with an XPD level better than 20.9 dB. The prototype exhibits exceptional azimuthal out-of-roundness values - better than 1.3 dB in its omnidirectional mode - and scan-invariant radiation with a maximum deviation of only 0.8 dB in its directional mode..University of Technology SydneyImmediate accessThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

High-Precision Detection Algorithm for Metal Workpiece Defects Based on Deep Learning

Computer vision technology is increasingly being widely applied in automated industrial production. However, the accuracy of workpiece detection is the bottleneck in the field of computer vision detection technology. Herein, a new object detection and classification deep learning algorithm called CSW-Yolov7 is proposed based on the improvement of the Yolov7 deep learning network. Firstly, the CotNet Transformer structure was combined to guide the learning of dynamic attention matrices and enhance visual representation capabilities. Afterwards, the parameter-free attention mechanism SimAM was introduced, effectively enhancing the detection accuracy without increasing computational complexity. Finally, using WIoUv3 as the loss function effectively mitigated many negative influences during training, thereby improving the model’s accuracy faster. The experimental results manifested that the [email protected] of CSW-Yolov7 reached 93.3%, outperforming other models. Further, this study also designed a polyhedral metal workpiece detection system. A large number of experiments were conducted in this system to verify the effectiveness and robustness of the proposed algorithm

Extracranial metastases of high-grade glioma: the clinical characteristics and mechanism

Abstract Background This presentation of two cases and literature review discusses the epidemiology, clinical manifestations, pathogenesis, diagnosis, treatment, and prognosis of high-grade glioma with extracranial metastases. Methods A retrospective analysis of the clinical features of two cases of malignant glioma, including metastatic sites, pathological data, and treatment methods, and a literature review was performed. Results Two patients developed extracranial metastases within 1 year after surgery for primary glioma. One patient developed cervical lymph node and bone metastases while the other developed bone metastases, and both patients died within 2 months after the diagnosis of the extracranial metastasis. Conclusion Extracranial metastases may develop from malignant gliomas. According to the literature, the most common extracranial site is intraspinal (along the neural axis), followed by the vertebrae, lungs, liver, and lymph nodes. The complex metastatic mechanism remains unclear, and the prognosis is very poor, with a survival duration of less than 6 months

Galectin-1 overexpression induces normal fibroblasts translate into cancer-associated fibroblasts and attenuates the sensitivity of anlotinib in lung cancer

We aimed to investigate galectin-1 overexpression induces normal fibroblasts (NFs) translates into cancer-associated fibroblasts (CAFs). Galectin-1 overexpression was conducted in Human embryonic lung fibroblasts (HFL1) cell. The motilities of H1299 and A549 cells were measured. Human umbilical vein endothelial cell (HUVEC) proliferation and tube formation ability were assessed. Tumor volume and tumor weight was recorded. Cells motilities were increased, while apoptosis rates were decreased after CMs co-cultured. B-cell lymphoma-2 (Bcl-2) expression level was increased, while Bcl2-associatedX (Bax) and cleaved-caspase3 decreased. CMs treatment enhanced HUVEC proliferation and tube formation. Tumor volume and weight in CMs treated mice were increased, and the sensitivity of anlotinib in co-cultured cells was decreased. Our results revealed that galectin-1 overexpression induced NFs translated into CAFs

Selenium Nanoparticles Attenuate Cobalt Nanoparticle-Induced Skeletal Muscle Injury: A Study Based on Myoblasts and Zebrafish

Cobalt alloys have numerous applications, especially as critical components in orthopedic biomedical implants. However, recent investigations have revealed potential hazards associated with the release of nanoparticles from cobalt-based implants during implantation. This can lead to their accumulation and migration within the body, resulting in adverse reactions such as organ toxicity. Despite being a primary interface for cobalt nanoparticle (CoNP) exposure, skeletal muscle lacks comprehensive long-term impact studies. This study evaluated whether selenium nanoparticles (SeNPs) could mitigate CoNP toxicity in muscle cells and zebrafish models. CoNPs dose-dependently reduced C2C12 viability while elevating reactive oxygen species (ROS) and apoptosis. However, low-dose SeNPs attenuated these adverse effects. CoNPs downregulated myogenic genes and α-smooth muscle actin (α-SMA) expression in C2C12 cells; this effect was attenuated by SeNP cotreatment. Zebrafish studies confirmed CoNP toxicity, as it decreased locomotor performance while inducing muscle injury, ROS generation, malformations, and mortality. However, SeNPs alleviated these detrimental effects. Overall, SeNPs mitigated CoNP-mediated cytotoxicity in muscle cells and tissue through antioxidative and antiapoptotic mechanisms. This suggests that SeNP-coated implants could be developed to eliminate cobalt nanoparticle toxicity and enhance the safety of metallic implants

Cervical <i>Staphylococcus aureus</i> Infection after Receiving the Third Dose of COVID-19 Vaccination: A Case Report

Introduction: Vaccination is one of the most effective ways to control the COVID-19 pandemic. However, as the number of people vaccinated against COVID-19 continues to increase, there are more reports on the safety of vaccines. So far, there have been no reported cases of spinal infection associated with COVID-19 vaccination. Recently, we admitted a patient who developed cervical Staphylococcus aureus infection resulting in high paraplegia after receiving the third dose of COVID-19 vaccine when the symptoms of cold did not completely disappear. Case presentation: The patient was a 70-year-old man who received the third injection of COVID-19 vaccine when the cold symptoms were not completely gone. On the day after the injection, the patient developed severe neck and shoulder pain, accompanied by numbness and fatigue in the limbs. MRI examination of the cervical spine on day 6 after vaccination showed no obvious signs of infection. The patient had progressive weakness in the extremities. On the ninth day after vaccination, the patient developed paralysis of both lower limbs and significant sensory loss. Cervical abscess and cervical spinal cord injury were considered for cervical CT and MRI examination on the 15th day after vaccination. We used an anterior approach to remove as much of the lesion as possible. Staphylococcus aureus was detected and antibiotic treatment was continued after surgery. The patient’s pain symptoms were significantly relieved, which prevented the abscess from further pressing the spinal cord and provided possible conditions for the recovery of neurological function in the later stage. Conclusion: This case is the first reported cervical Staphylococcus aureus infection resulting in high paraplegia after receiving the third dose of COVID-19 vaccine with low immunity. This case raises awareness of this rare but potentially life-threatening adverse reaction, and reminds people to hold off when their immune system is weakened

Distribution of metastasis in the brain in relation to the hippocampus: a retrospective single-center analysis of 565 metastases in 116 patients

Abstract Objective To examine the distribution of brain metastases (BM) in relation to the hippocampus, so as to determine the risk of metastasis in the hippocampus, and thus provide experimental evidence for the hippocampal avoidance (HA) in patients with BM during radiotherapy. Methods (1) For the retrospective analysis of 116 patients diagnosed with malignancies, confirmed as BM, from December 2014 to December 2016 at the First Affiliated Hospital of Bengbu Medical College. We obtained the T1-weighted, postcontrast axial, sagittal, and coronal Magnetic Resonance imaging (MRI) images f the patients, in supine position, using the head restraints and head thermoplastic masks to adjust the positioning, with computed tomography (CT) positioning scan ranging from the head to the mandible (layer thickness: 3 mm). CT and MRI images were fused on a Philips Pinnacle v9.8 treatment planning system;(2) Every metastasis of the 565 metastases was contoured;(3) hippocampus were contoured, and hippocampus with 5 mm expansion envelopes were analyzed;(4) Using the SPSS 16.0 software, we analyzed the relation between the distribution and age, sex, Karnofsky performance status (KPS), primary site, aggregate volume of intracranial metastases and the whole brain. The data were analyzed using a binary logistic regression analysis method, with two-sided P 0.05). Conclusion This study showed a low risk for the perihippocampal metastases (PHM) and no significant correlation between PHM and age, sex, KPS, primary site, aggregate volume of intracranial metastases and the whole brain. Accordingly, it is may be acceptable to avoid the perihippocampal region during whole brain radiotherapy

LocusFocus: Web-based colocalization for the annotation and functional follow-up of GWAS.

Genome-wide association studies (GWAS) have primarily identified trait-associated loci in the non-coding genome. Colocalization analyses of SNP associations from GWAS with expression quantitative trait loci (eQTL) evidence enable the generation of hypotheses about responsible mechanism, genes and tissues of origin to guide functional characterization. Here, we present a web-based colocalization browsing and testing tool named LocusFocus (https://locusfocus.research.sickkids.ca). LocusFocus formally tests colocalization using our established Simple Sum method to identify the most relevant genes and tissues for a particular GWAS locus in the presence of high linkage disequilibrium and/or allelic heterogeneity. We demonstrate the utility of LocusFocus, following up on a genome-wide significant locus from a GWAS of meconium ileus (an intestinal obstruction in cystic fibrosis). Using LocusFocus for colocalization analysis with eQTL data suggests variation in ATP12A gene expression in the pancreas rather than intestine is responsible for the GWAS locus. LocusFocus has no operating system dependencies and may be installed in a local web server. LocusFocus is available under the MIT license, with full documentation and source code accessible on GitHub at https://github.com/naim-panjwani/LocusFocus