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Since December 2019, the novel coronavirus disease 2019 (COVID-19) has claimed the lives of more than 3.75 million people worldwide. Consequently, methods for accurate COVID-19 diagnosis and classification are necessary to facilitate rapid patient care and terminate viral spread. Lung infection segmentations are useful to identify unique infection patterns that may support rapid diagnosis, severity assessment, and patient prognosis prediction, but manual segmentations are time-consuming and depend on radiologic expertise. Deep learning-based methods have been explored to reduce the burdens of segmentation; however, their accuracies are limited due to the lack of large, publicly available annotated datasets that are required to establish ground truths. For these reasons, we propose a semi-automatic, threshold-based segmentation method to generate region of interest (ROI) segmentations of infection visible on lung computed tomography (CT) scans. Infection masks are then used to calculate the percentage of lung abnormality (PLA) to determine COVID-19 severity and to analyze the disease progression in follow-up CTs. Compared with other COVID-19 ROI segmentation methods, on average, the proposed method achieved improved precision ( 47.49 % ) and specificity ( 98.40 % ) scores. Furthermore, the proposed method generated PLAs with a difference of ± 3.89 % from the ground-truth PLAs. The improved ROI segmentation results suggest that the proposed method has potential to assist radiologists in assessing infection severity and analyzing disease progression in follow-up CTs.Successful implementation of solutions to reach the UN Sustainable Development Goals (SDGs) depends on harnessing synergistic interactions among SDGs and effective engagement among a diverse group of societal stakeholders. This paper presents a framework and case study for a design and engagement process in which the university takes the lead in the co-creation of SDG solutions. The model supports university-led efforts by leveraging three elements (i) inherent synergies across SDGs, (ii) modes of solution identification, design, and implementation, and (iii) modes of stakeholder involvement and interactions. Using an integration of human-centered design (HCD) and shared-action learning (SAL), we document a case led by a large, public, research-oriented university on how different stakeholders participated in the co-creation process to find solutions. Based on the experience of about 50 students over 4 years in support of SDG implementation in Indonesia, the initiative leveraged synergies within SDG 1, 2, and 5 (related to increasing income-generating power for women and indigenous people) and SDG 7 (use of solar energy for fish preservation and crop processing). Throughout the process, interactions with stakeholders took place during design workshop courses, community consultations, mentoring and internships programs, partnering with companies and local universities and government, site visits, and immersions in local communities. The HCD-SAL model established a system for monitoring impacts across all stakeholders, particularly how the projects helped increase communities' economic well-being. This model provides guidance for universities to develop genuine stakeholder engagement and support for finding and continuously improving SDG solutions.
The online version contains supplementary material available at 10.1007/s11625-022-01128-9.
The online version contains supplementary material available at 10.1007/s11625-022-01128-9.Background The clinical utility of mRNA cargo in exosomes is unclear, although exosomes have potential as non-invasive biomarkers. This study aimed to investigate the feasibility of exosomal mRNA sequencing for monitoring disease status and predicting outcomes in non-Hodgkin lymphoma (NHL) patients. Methods Exosomes were isolated from archived serum samples of 33 patients with NHL who were registered into our prospective cohort diffuse large B-cell lymphoma (DLBCL, n = 17), intravascular B-cell lymphoma (IVL, n = 1), primary mediastinal large B-cell lymphoma (PMBL, n = 4), follicular lymphoma (FL, n = 3), mantle cell lymphoma (MCL, n = 3), and extranodal NK/T-cell lymphoma (ENKTL, n = 5). Exosomal mRNA sequencing was performed, and its concordance with clinical course was analyzed and compared with those of circulating tumor DNA (ctDNA) mutations. Results Exosomal mRNA sequencing was performed successfully in 26 cases (79%, 26/33), whereas the remaining seven cases were not completed due to their small amount of RNA. The exosomal mRNA sequencing of DLBCL showed gene expression profiles consistent with activated B-cell-like and germinal center type. The longitudinal assessment of exosomal mRNA sequencing results in accordance with the clinical course showed that the post-treatment changes of exosomal mRNA expression were more consistent with treatment outcome than were those of ctDNA mutations. In particular, the exosomal mRNA expression of genes such as BCL2 and BCL6 was increased at the time of disease progression in DLBCL and FL patients. Conclusions This study demonstrated the feasibility of exosomal mRNA expression profiles as a biomarker for NHL patients. Our results might provide the rationale for studies to explore the potential of exosomal mRNA as a biomarker in NHL patients.Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumour with a poor prognosis and a high mortality rate. It is of great significance to explore sensitive or specific biomarkers for early diagnosis and prognosis. We first examined the metabolome and gut microbiota of resectable and unresectable PDAC patients to comprehensively investigate the characteristics of PDAC at different stages of progression. At the genus level, we found that the relative abundances of Alistipes, Anaerostipes, Faecalibacterium and Parvimonas were reduced in unresectable PDAC patients, whereas Pseudonocardia, Cloacibacterium, Mucispirillum, and Anaerotruncus were increased. Metabolomics analysis showed that the main changed metabolites were amino acids, carnitine derivatives, lipids and fatty acids. ROC analysis showed that Oleic acid, Linoleic acid, Palmitic acid, Linoelaidyl carnitine, 2-Octenedioic acid, 3R, 7R-1,3,7-Octanetriol, LysoPE (P-160/00) and 3-Hydroxyanthranilic acid had high AUC values (>0.9). Function and neism.Purpose Exosome component 5 (EXOSC5) is a non-catalytic component of the RNA exosome complex, which is interacted with the Zinc-finger antiviral protein to degrade the target RNA and aberrantly expressed in various malignances. We explored the molecular mechanisms and biological roles by which EXOSC5 promotes the progression of GC. Methods We used quantitative real-time PCR, Western blotting and immunohistochemistry to analyze EXOSC5 expression in GC samples. An GC organoid-based functional model was assessed, and cancer cell CCK-8 assay, colony formation assay and flow cytometry were performed to reveal the role of EXOSC5 in GC cell proliferation and tumorigenesis. In vivo, nude mice tumorigenesis assay were performed to explore the effects of EXOSC5 knockdown on growth of GC. The roles of EXOSC5 on AKT and STAT3 signaling pathways were measured by Western blot. Results The expression of EXOSC5 was up-regulated in GC tissues and cell lines compared with normal group, and highly expressed EXOSC5 indicated a poorer clinical outcome for GC patients and was positively correlated with tumor size and TNM stage. EXOSC5 overexpression facilitated the growth of GC cells and organoids, while EXOSC5 downregulation inhibited proliferation and induced G1/S phase transition arrest. Moreover, mechanistic studies demonstrated that EXOSC5 increased cyclinD1 expression levels and decreasing the expression levels of p21 and p27 via regulation of the AKT and STAT3 pathway. AP-III-a4 concentration Conclusion The expression of EXOSC5 is upregulated and correlated with tumorigenesis and poor prognosis of GC. EXOSC5 increases GC proliferation partly through activating AKT and STAT3 pathways.Background More than 40% of lung cancer patients are diagnosed at ages over 70. However, the genomic and clinical characteristics among them remain elusive. Here, we performed targeted capture sequence to characterize the mutational spectrum of Chinese lung adenocarcinoma (LUAD) patients across ages. Patients and Methods 2025 LUAD patients were divided into three groups young (≤50 years old) (n=416, 20.54%), intermediate (51~69 years old) (n=1271, 62.77%), and aged (≥70 years old) (n=338, 16.69%). 1,021-gene panel and 59-gene panel were used for sequencing with tissue samples. Genetic alterations and tumor mutation burden (TMB) in LUAD patients were investigated. Results The frequency of mutations affecting 20 genes were significantly higher in aged group than in young group, and fourteen of them were not reported before, including involved in cell cycle/apoptosis signaling (FAT1, FAT2), DNA damage repair (FANCA and FANCM), chromatin histone modification (KDM6A), RTK/RAS/PI3K signaling (FLT4 and MTOR), NOTCH signaling (NOTCH1, NOTCH2 and NOTCH4) and other signaling pathway or cellular regulatory factor (KEAP1, ASXL1, EPHB1 and ABCB1). Six previously reported mutated genes (RBM10, KRAS, LRP1B, CDKN2A and KMT2C/D) were also significantly more frequent in aged group. Among clinical actionable mutation sites, KRAS mutation was presented more common in aged group; both MET exon 14 skipping and MET amplification were significantly positively correlated with old age; the fusions of ALK, ROS1, RET and ERBB2 exon 20 insertion were less frequent in aged group. Furthermore, a higher level of TMB was found in aged group compared with young group. Conclusion In this study, we revealed the differences of somatic genetic mutations and TMB between young and aged LUAD patients, which may provide directions of targeted therapy and advantages of immunotherapy for the elderly in the future.Purpose In this study we sought to investigate factors associated to dysphagia and subsequent need for percutaneous gastrostomy (PEG) usage, in patients with head and neck cancer receiving radiation therapy. Methods The records of 123 patients with non-metastatic, stage I-IV head and neck cancer who were submitted to radiation therapy were retrospectively reviewed. Logistic regression models were used to investigate for associations between the outcomes of interest (grade ≥2 dysphagia and need for [PEG] usage) and potential predictive factors. Results Mean dose to pharyngeal constrictor muscles (OR=1.08, p=.002), concurrent chemotherapy (OR=3.78, p=0.015) and upper aerodigestive tract malignancies (OR=3.27, p=0.044) were associated with dysphagia grade≥2. A threshold of constrictors mean dose for dysphagia manifestation was also identified at 43 Gy (OR=4.51, p=0.002). Need for PEG use was correlated with definitive treatment (OR=7.03, p=.022), nasopharyngeal (OR=12.62, p=0.003), upper aerodigestive tract (OR=9.12, p=0.007) or occult primary malignancies (OR=10.78, p=0.016). Conclusion Patients suffering from upper aerodigestive tract malignancies, those with calculated constrictors mean dose >43 Gy, or planned to receive concurrent chemotherapy-radiotherapy should be closely monitored during treatment for dysphagia manifestation. Prophylactic PEG could be considered for patients receiving definitive therapy of the nasopharynx, upper aerodigestive tract or occult primary malignancies.
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