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7% (2 patients). Median overall survival post-salvage resection was 24 months. The median overall survival for an R1 resection was 5.3 months versus 108 months for an R0 resection (p=0.001). Persistent pN1+ salvage resections also did less well compared to pN0, 8.9 vs 28.2 months (p=0.06). For patients who underwent non-extended salvage resection ("simple lobectomy" or "simple pneumonectomy"), the median overall survival was 108.4 months, versus 8.9 months for extended salvage resections (p = 0.02). Conclusions With proper patient selection, salvage lung resections can be performed with acceptable morbidity, mortality, and oncologic outcomes, particularly when a ypN0R0 resection can be achieved by non-extended surgical means.Background Successful surgical treatment of patients with Mycobacterium avium complex pulmonary disease is thought to require complete removal of parenchymal destructive lesions. This study aimed to evaluate the short- and long-term outcomes and the predictors of microbiological recurrence after surgery for Mycobacterium avium complex pulmonary disease. Methods We conducted a retrospective review of 184 patients undergoing unilateral lung resection for Mycobacterium avium complex pulmonary disease at a single center in Japan between January 2008 and December 2017. Results The median age of the 184 patients was 55.5 years; 133 (72.3%) were females. All but 2 patients had anatomical lung resection. One hundred sixteen (63.0%) patients had limited disease and underwent complete resection; the remaining 68 (37.0%) patients had extensive disease and underwent "debulking" surgery. No operative mortalities occurred. Twenty-one morbidities occurred in 18 of 184 (9.8%) patients, including 3 (1.6%) bronchopleural fistulae. Postoperative sputum-negative status was achieved in 183 (99.5%) patients. Microbiological recurrences occurred in 15 (8.2%) patients. By multivariate analysis, extensive disease was an independent risk factor for recurrence (hazard ratio, 5.432; 95% confidence interval, 1.372-21.50; p = 0.016). Recurrence-free rates were significantly higher in patients with limited disease compared with those with extensive disease (99.0%, 97.4% and 95.0% vs 93.0%, 89.2% and 75.1% at 1, 3, and 5 years, respectively; p less then 0.001). Conclusions Complete resection of parenchymal destructive lesions can achieve excellent microbiological control for patients with limited Mycobacterium avium complex pulmonary disease. The efficacy of "debulking" surgery in patients with extensive disease needs further investigation.We present the successful use of surgical embolectomy (SE) without systemic anticoagulation to treat a complicated case of pulmonary embolism (PE). The patient presented with an embolic cerebrovascular accident and subsequently developed a massive PE. Due to risk of hemorrhagic transformation, the decision was made to proceed with emergent SE on VA-ECMO support without anticoagulation. The surgery was performed without complication. The potential to perform SE without anticoagulation could potentially decrease the incidence of surgical bleeding and make SE a therapeutic option for patients with contraindications to anticoagulation. Further research is needed to substantiate the efficacy of this treatment strategy.Background Fluid overload contributes to poor outcomes after neonatal cardiac surgery. The optimal strategy to mitigate fluid overload related morbidity is unknown. The utility of prophylactic peritoneal dialysis remains controversial. We aimed to assess the impact of prophylactic peritoneal dialysis on outcomes and hypothesized that prophylactic dialysis would be associated with less fluid overload and improved outcomes in neonates undergoing the arterial switch operation. Methods A Single center retrospective analysis of 41 consecutive neonates between 6/2010-3/2016 undergoing the arterial switch operation was performed. Fluid balance and other outcomes were compared between those receiving peritoneal dialysis (n=25) vs. those who did not (n=16). Results Demographics were similar between groups, except cardiopulmonary bypass duration which was significantly longer in the dialysis group (125±20 minutes) compared to the no dialysis group (109±15 minutes)(p = 0.01). Median time to dialysis initiation and termination from cardiac intensive care unit admission were 9.1 hours (IQR7-9.8) and 58.7 hours (IQR44-76.1) respectively. Cumulative fluid balance in the dialysis group was significantly more negative compared to the no dialysis group across all 7 post-operative days. In the multivariable analysis, use of dialysis was associated with a 42% (RR0.58, 95% CI 0.4-0.85, p less then 0.01) and 34% (RR0.66, 95% CI0.47-0.94, p = 0.02) reduction in hours of mechanical ventilation and intensive care length of stay respectively. Utilization of dialysis was associated with lower hospital costs (p less then 0.01). Conclusions Prophylactic peritoneal dialysis after the arterial switch operation is associated with improved post-operative outcomes without increased hospital costs (Visual Abstract).Understanding adaptive immunity to SARS-CoV-2 is important for vaccine development, interpreting coronavirus disease 2019 (COVID-19) pathogenesis, and calibration of pandemic control measures. Using HLA class I and II predicted peptide "megapools," circulating SARS-CoV-2-specific CD8+ and CD4+ T cells were identified in ∼70% and 100% of COVID-19 convalescent patients, respectively. CD4+ T cell responses to spike, the main target of most vaccine efforts, were robust and correlated with the magnitude of the anti-SARS-CoV-2 IgG and IgA titers. The M, spike, and N proteins each accounted for 11%-27% of the total CD4+ response, with additional responses commonly targeting nsp3, nsp4, ORF3a, and ORF8, among others. For CD8+ T cells, spike and M were recognized, with at least eight SARS-CoV-2 ORFs targeted. Importantly, we detected SARS-CoV-2-reactive CD4+ T cells in ∼40%-60% of unexposed individuals, suggesting cross-reactive T cell recognition between circulating "common cold" coronaviruses and SARS-CoV-2.Enhanced blood vessel (BV) formation is thought to drive tumor growth through elevated nutrient delivery. However, this observation has overlooked potential roles for mural cells in directly affecting tumor growth independent of BV function. Here we provide clinical data correlating high percentages of mural-β3-integrin-negative tumor BVs with increased tumor sizes but no effect on BV numbers. Mural-β3-integrin loss also enhances tumor growth in implanted and autochthonous mouse tumor models with no detectable effects on BV numbers or function. At a molecular level, mural-cell β3-integrin loss enhances signaling via FAK-p-HGFR-p-Akt-p-p65, driving CXCL1, CCL2, and TIMP-1 production. In particular, mural-cell-derived CCL2 stimulates tumor cell MEK1-ERK1/2-ROCK2-dependent signaling and enhances tumor cell survival and tumor growth. Overall, our data indicate that mural cells can control tumor growth via paracrine signals regulated by β3-integrin, providing a previously unrecognized mechanism of cancer growth control.Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly across the USA, causing extensive morbidity and mortality, particularly in the African American community. Autopsy can considerably contribute to our understanding of many disease processes and could provide crucial information to guide management of patients with coronavirus disease 2019 (COVID-19). selleck kinase inhibitor We report on the relevant cardiopulmonary findings in, to our knowledge, the first autopsy series of ten African American decedents, with the cause of death attributed to COVID-19. Methods Autopsies were performed on ten African American decedents aged 44-78 years with cause of death attributed to COVID-19, reflective of the dominant demographic of deaths following COVID-19 diagnosis in New Orleans. Autopsies were done with consent of the decedents' next of kin. Pulmonary and cardiac features were examined, with relevant immunostains to characterise the inflammatory response, and RNA labelling and electron microscopy on representative sections. Findings Important findings include the presence of thrombosis and microangiopathy in the small vessels and capillaries of the lungs, with associated haemorrhage, that significantly contributed to death. Features of diffuse alveolar damage, including hyaline membranes, were present, even in patients who had not been ventilated. Cardiac findings included individual cell necrosis without lymphocytic myocarditis. There was no evidence of secondary pulmonary infection by microorganisms. Interpretation We identify key pathological states, including thrombotic and microangiopathic pathology in the lungs, that contributed to death in patients with severe COVID-19 and decompensation in this demographic. Management of these patients should include treatment to target these pathological mechanisms. Funding None.Lysine 2-hydroxyisobutyrylation (Khib) is a newly discovered post-translational modification (PTM) across eukaryotes and prokaryotes in recent years, which plays a significant role in diverse cellular functions. Accurate prediction of Khib sites is a first-crucial step to decipher its molecular mechanism and urgently needed. In this work, based on a large benchmark datasets in multi-species, a novel online species-specific prediction tool, namely KhibPred, was developed to identify Khib sites. Four types of feature strategies, including sequence-based information, physicochemical properties and evolutionary-derived information, were applied to represent a wide range of protein sequences, and the random forest was used to build the optimal feature datasets. Moreover, six representative machine learning (ML) methods were trained and comprehensively discussed and compared for each organism. Data analyses suggested that the unique protein sequence preferences were discovered for each species. When evaluated on independent test datasets, the area under the receiver operating characteristic curves (AUCs) achieved 0.807, 0.781, 0.825 and 0.831 for Saccharomyces cerevisiaes, Physcomitrella patens, Rice Seeds and HeLa cells, respectively. The satisfactory results imply that KhibPred is a promising computational tool. The online predictor can be freely available at http//bioinfo.ncu.edu.cn/KhibPred.aspx.Cytosine methylation is the leading epigenetic modification on DNA playing a role in gene regulation. Methylation can occur in cytosines of any nucleic acids in cytosol (as mitochondrial DNA, mtDNA) and in nuclear DNA (ncDNA). mtDNA exists as multiple copies within numerous mitochondria. This suggests that the number of mitochondria and mtDNA copy number can indicate the presence of a significant amount of DNA methylation within total DNA methylation detected. However, immunofluorescence method does not have a step to discriminate the staining between ncDNA and mtDNA. Antibodies used in immunological methods are methylation-specific but not selective for DNA type and they can bind to methylated cytosines in any DNA within the specimen. Current study aimed to understand whether mtDNA methylation interferes with the detection of nuclear DNA methylation by immunofluorescence and affinity enrichment (ELISA) in different mammalian cells. Experiments were performed to distinguish methylation between mtDNA and ncDNA.
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