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1.
Comput Methods Programs Biomed ; 196: 105632, 2020 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-32615491

RESUMO

BACKGROUND AND OBJECTIVE: The instantaneous wave-free ratio (iFR) has been proposed to estimate the hemodynamic severity of atherosclerotic stenosis in coronary arteries. The atherosclerotic stenosis in a proximal coronary artery could change its distal microcirculatory resistance (MR). However, there is a lack of investigation about the effect of MR variation on the blood flow and iFR of stenotic coronary arteries. We aim to investigate the changes of blood flow and iFR caused by distal MR variation. METHODS: Four three-dimensional models of coronary arteries were reconstructed from the computed tomography images of two normal cases and two cases with 74.9% and 96.4% (in area) stenoses in a large branch of left anterior descending artery (LAD). Computational fluid dynamics simulation was performed on each model under 6 MR situations: hyperemia as the reference situation, resting when MR was multiplied by 8/3 in all outlet branches, h-one-1.5 and h-one-2 when MR was multiplied by 1.5 and 2.0 in one branch (the stenotic, or the corresponding branch in normal case) of LAD, h-branches-1.5 and h-branches-2 when MR was multiplied by 1.5 and 2.0 in the stenotic/corresponding and its cognate branches. Flow rate and iFR of each outlet branch were then calculated and compared between different MR situations to investigate the effect of MR variation on flow rate and iFR. RESULTS: In the 74.9% stenosed and normal cases, referring to the hyperemia situation, the increase of MR in any branch significantly decreased its flow rate and increased its iFR, with limited effect on the flow rate (<3%) and iFR (<0.01) of other branches. However, in the 96.4% stenosed case, the doubled MR in the stenosed branch (h-one-2) significantly increased the flow rate (>10%) and iFR (>0.05) of its cognate branches. CONCLUSION: The increase of MR in a normal or mildly stenosed branch of coronary artery decreases its blood flow and increases its iFR, with limited effect on other branches. Whereas, the increase of MR in a severely stenotic large branch could significantly increase the flow velocity and iFR of its cognate branches.

2.
JAMA Netw Open ; 3(6): e205842, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32492161

RESUMO

Importance: There is a lack of studies exploring the performance of a deep learning survival neural network in non-small cell lung cancer (NSCLC). Objectives: To compare the performances of DeepSurv, a deep learning survival neural network with a tumor, node, and metastasis staging system in the prediction of survival and test the reliability of individual treatment recommendations provided by the deep learning survival neural network. Design, Setting, and Participants: In this population-based cohort study, a deep learning-based algorithm was developed and validated using consecutive cases of newly diagnosed stages I to IV NSCLC between January 2010 and December 2015 in a Surveillance, Epidemiology, and End Results database. A total of 127 features, including patient characteristics, tumor stage, and treatment strategies, were assessed for analysis. The algorithm was externally validated on an independent test cohort, comprising 1182 patients with stage I to III NSCLC diagnosed between January 2009 and December 2013 in Shanghai Pulmonary Hospital. Analysis began January 2018 and ended June 2019. Main Outcomes and Measures: The deep learning survival neural network model was compared with the tumor, node, and metastasis staging system for lung cancer-specific survival. The C statistic was used to assess the performance of models. A user-friendly interface was provided to facilitate the survival predictions and treatment recommendations of the deep learning survival neural network model. Results: Of 17 322 patients with NSCLC included in the study, 13 361 (77.1%) were white and the median (interquartile range) age was 68 (61-74) years. The majority of tumors were stage I disease (10 273 [59.3%]) and adenocarcinoma (11 985 [69.2%]). The median (interquartile range) follow-up time was 24 (10-43) months. There were 3119 patients who had lung cancer-related death during the follow-up period. The deep learning survival neural network model showed more promising results in the prediction of lung cancer-specific survival than the tumor, node, and metastasis stage on the test data set (C statistic = 0.739 vs 0.706). The population who received the recommended treatments had superior survival rates than those who received treatments not recommended (hazard ratio, 2.99; 95% CI, 2.49-3.59; P < .001), which was verified by propensity score-matched groups. The deep learning survival neural network model visualization was realized by a user-friendly graphic interface. Conclusions and Relevance: The deep learning survival neural network model shows potential benefits in prognostic evaluation and treatment recommendation with respect to lung cancer-specific survival. This novel analytical approach may provide reliable individual survival information and treatment recommendations.

3.
Front Immunol ; 11: 824, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32536909

RESUMO

The momentous discovery of phagocytic activity in teleost B cells has caused a dramatic paradigm shift from the belief that phagocytosis is performed mainly by professional phagocytes derived from common myeloid progenitor cells, such as macrophages/monocytes, neutrophils, and dendritic cells. Recent advances on phagocytic B cells and their microbicidal ability in teleost fish position B cells at the crossroads, bridging innate with adaptive immunity. Most importantly, an increasing body of experimental evidence demonstrates that, in both teleosts and mammals, phagocytic B cells can recognize, take up, and destroy particulate antigens and then present those processed antigens to CD4+ T cells to elicit adaptive immune responses and that the phagocytosis is mediated by pattern recognition receptors and involves multiple cytokines. Thus, current findings collectively indicate that teleost phagocytic B cells, as well as their counterpart mammalian B1-B cells, can be considered one kind of professional phagocyte. The aim of this review is to summarize recent advances regarding teleost phagocytic B cells, with a particular focus on the recognizing receptors and modulating mechanisms of phagocytic B cells and the process of antigen presentation for T-cell activation. We also attempt to provide new insights into the adaptive evolution of the teleost fish phagocytic B cell on the basis of its innate and adaptive roles.

4.
Dev Comp Immunol ; 111: 103749, 2020 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-32505616

RESUMO

The Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway is pivotal in immune responses for a variety of pathogens in both vertebrates and invertebrates. Domeless (Dome), as a unique cytokine receptor, involves in the upstream JAK/STAT pathway in invertebrates. In this study, the full-length cDNA sequence of a cytokine receptor Dome was identified from red claw crayfish Cherax quadricarinatus (named as CqDome), which contained an open reading frame of 4251 bp, encoding 1416 amino acids. The CqDome contained extracellular conservative domains of a signal peptide, two cytokine binding modules (CBM), three fibronectin-type-III-like (FN3) domains and a transmembrane region. Tissue distribution analysis showed that CqDome generally expressed in all the tissues selected with a high expression in hemocyte. The gene expression of both the viral immediately early gene (IE1) and a late gene envelope protein VP28 of white spot syndrome virus (WSSV) were significantly decreased after gene silencing of CqDome in crayfish haematopoietic tissue (Hpt) cells, indicating a key role of CqDome in promoting WSSV infection. Furthermore, the phosphorylation level of CqSTAT was significantly inhibited by gene silencing of CqDome in Hpt cells, indicating that CqDome participated in signal transduction of JAK/STAT pathway in red claw crayfish. These data together suggest that CqDome is likely to promote WSSV infection via JAK/STAT pathway, which sheds new light on further elucidation of the pathogenesis of WSSV.

5.
Comput Biol Chem ; 86: 107261, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32361585

RESUMO

Mutant isocitrate dehydrogenase 2 (mIDH2) is an emerging target for the treatment of cancer. AG-221 is the first mIDH2 inhibitor approved by the FDA for acute myeloid leukemia treatment, but its acquired resistance has recently been observed, necessitating the development of new inhibitor. In this study, a multi-step virtual screening protocol was employed for the analysis of a large database of compounds to identify potential mIDH2 inhibitors. To this end, we firstly utilized molecular dynamics (MD) simulations and binding free energy calculations to elucidate the key factors affecting ligand binding and drug resistance. Based on these findings, the receptor-ligand interaction-based pharmacophore (IBP) model and hierarchical docking-based virtual screening were sequentially carried out to assess 212,736 compounds from the Specs database. The resulting hits were finally ranked by PAINS filter and ADME prediction and the top compounds were obtained. Among them, six molecules were identified as mIDH2 putative inhibitors with high selectivity by interacting with the capping residue Asp312. Furthermore, subsequent docking and MD experiments demonstrated that compound V2 might have potential inhibitory activity against the AG-221-resistant mutants, thereby making it a promising lead for the development of novel mIDH2 inhibitors.

6.
Front Immunol ; 11: 560, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32425924

RESUMO

Cell-based immunotherapies have tremendous potential to treat many diseases, such as activating immunity in cancer or suppressing it in autoimmune diseases. Most cell-based cancer immunotherapies in the clinic provide adjuvant signals through genetic engineering to enhance T cell functions. However, genetically encoded signals have minimal control over dosing and persist for the life of a cell lineage. These properties make it difficult to balance increasing therapeutic efficacy with reducing toxicities. Here, we demonstrated the potential of phospholipid-coupled ligands as a non-genetic system for immune cell engineering. This system provides simple, controlled, non-genetic adjuvant delivery to immune cells via lipid-mediated insertion into plasma membranes. Lipid-mediated insertion (termed depoting) successfully delivered Toll-like receptor (TLR) ligands intracellularly and onto cell surfaces of diverse immune cells. These ligands depoted into immune cells in a dose-controlled fashion and did not compete during multiplex pairwise loading. Immune cell activation could be enhanced by autocrine and paracrine mechanisms depending on the biology of the TLR ligand tested. Depoted ligands functionally persisted on plasma membranes for up to 4 days in naïve and activated T cells, enhancing their activation, proliferation, and skewing cytokine secretion. Our data showed that depoted ligands provided a persistent yet non-permanent adjuvant signal to immune cells that may minimize the intensity and duration of toxicities compared to permanent genetic delivery. Altogether, these findings demonstrate potential for lipid-mediated depoting as a universal cell engineering approach with unique, complementary advantages to other cell engineering methods.

7.
ChemSusChem ; 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32394542

RESUMO

The emerging generation of flexible energy storage devices has accelerated the research pace in terms of new materials, new processing techniques, and new designs that can meet the demands of mechanical stability upon bending or stretching at an acceptable cost, without compromising their electrochemical performance. Among the materials currently explored, biomass-derived materials have received extensive attention, because they are renewable, low in cost, earth-abundant and structurally diverse. This review is focused on fundamentals and applications of the bio-derived material bacterial cellulose (BC) in flexible electrochemical energy storage systems. Specifically, recent advances are summarized in the utilization of BC in stretchable substrates, carbonaceous species, and scaffolds for flexible core component construction. Finally, several perspectives related to BC-based materials for flexible electrochemical energy storages are proposed, aiming to provide possible future research directions in these fields.

8.
Biomed Eng Online ; 19(1): 21, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32295576

RESUMO

BACKGROUND: As one of the major complications of diabetes, diabetic retinopathy (DR) is a leading cause of visual impairment and blindness due to delayed diagnosis and intervention. Microaneurysms appear as the earliest symptom of DR. Accurate and reliable detection of microaneurysms in color fundus images has great importance for DR screening. METHODS: A microaneurysms' detection method using machine learning based on directional local contrast (DLC) is proposed for the early diagnosis of DR. First, blood vessels were enhanced and segmented using improved enhancement function based on analyzing eigenvalues of Hessian matrix. Next, with blood vessels excluded, microaneurysm candidate regions were obtained using shape characteristics and connected components analysis. After image segmented to patches, the features of each microaneurysm candidate patch were extracted, and each candidate patch was classified into microaneurysm or non-microaneurysm. The main contributions of our study are (1) making use of directional local contrast in microaneurysms' detection for the first time, which does make sense for better microaneurysms' classification. (2) Applying three different machine learning techniques for classification and comparing their performance for microaneurysms' detection. The proposed algorithm was trained and tested on e-ophtha MA database, and further tested on another independent DIARETDB1 database. Results of microaneurysms' detection on the two databases were evaluated on lesion level and compared with existing algorithms. RESULTS: The proposed method has achieved better performance compared with existing algorithms on accuracy and computation time. On e-ophtha MA and DIARETDB1 databases, the area under curve (AUC) of receiver operating characteristic (ROC) curve was 0.87 and 0.86, respectively. The free-response ROC (FROC) score on the two databases was 0.374 and 0.210, respectively. The computation time per image with resolution of 2544×1969, 1400×960 and 1500×1152 is 29 s, 3 s and 2.6 s, respectively. CONCLUSIONS: The proposed method using machine learning based on directional local contrast of image patches can effectively detect microaneurysms in color fundus images and provide an effective scientific basis for early clinical DR diagnosis.

9.
Am J Nephrol ; 51(6): 453-462, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32349004

RESUMO

BACKGROUND: The lack of consensus criteria of acute on chronic kidney injury (ACKI) affects the judgment for its clinical prognosis. METHODS: In this study, we analyzed the data from 711,615 hospitalized adults who had at least 2 serum creatinine (SCr) tests within 30 days. We estimated the reference change value (RCV) of SCr given initial SCr level in adults without known risks of acute kidney injury other than chronic kidney disease (CKD). We proposed a criterion for ACKI based on the RCV of SCr (cROCK), which defined ACKI as a ≥25% increase in SCr in 7 days. We validated cROCK by its association with the risks of in-hospital mortality, death after discharge, and CKD progression in a large cohort of patients with CKD stage 3. RESULTS: In 21,661 patients with CKD stage 3, a total of 3,145 (14.5%), 1,512 (7.0%), and 221 (1.0%) ACKI events were detected by both cROCK and Kidney Disease Improving Global Outcomes (KDIGO), cROCK only, and KDIGO only, respectively. cROCK detected 40% more ACKI events than KDIGO. Compared with patients without ACKI by both definitions, those with cROCK- but not KDIGO-defined ACKI had a significantly increased risk of in-hospital mortality (hazard ratio [HR] 5.53; 95% CI 3.75-8.16), death after discharge (HR 1.51; 95% CI 1.21-1.83), and CKD progression (OR 5.65; 95% CI 3.05-10.48). CONCLUSIONS: RCV-based criterion (cROCK) for ACKI is clinically valid in that it has a substantially improved sensitivity in identifying patients with high risk of adverse outcomes.

10.
Dev Comp Immunol ; 107: 103665, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32147597

RESUMO

Invertebrates rely solely on the innate immune system to protect against virus infection, while the viral infection must rely on the transcriptional system of the host cell to achieve the expression of viral genes, which is naturally regulated by the host's transcriptional system. However, the mechanism of the host against viral transcription in host cells is still poorly understood in crustaceans. Previously, we found that the partial transcript sequence of a negative elongation factor E (named as CqNELF-E) was up-regulated in a differentially expressed transcriptome library of the haematopietic tissue (Hpt) cells from red claw crayfish Cherax quadricarinatus upon white spot syndrome virus (WSSV) infection, suggesting a possible role of CqNELF-E in WSSV-host interaction. In the present study, we revealed the function of CqNELF-E. The full-length cDNA sequence of CqNELF-E was identified with 1726 bp from red claw crayfish, which contained an open reading frame of 816 bp, encoding 271 amino acids. Amino acid sequencing analysis revealed that the CqNELF-E had a conserved RNA recognition motif (RRM) and a leucine zipper motif (LZM). Tissue distribution analysis showed that CqNELF-E was widely expressed in various tissues with the highest expression in muscle, relatively abundant in Hpt and the lowest presence in heart. Interestingly, the gene expression of CqNELF-E was significantly up-regulated at both 6 and 12 hpi after WSSV infection in Hpt cell cultures in red claw crayfish. In addition, the expression of both the viral immediately early gene (IE) 1 (IE1) and a late gene envelope protein VP28 were significantly increased after gene silencing of CqNELF-E in Hpt cells, indicating the potential suppression role of CqNELF-E against the viral infection. Further study revealed that the CqNELF-E had an inhibitory effect on the promoter activity of WSSV IE genes WSV051, WSV069 (IE1) and WSV083 by a dual luciferase reporter gene assay. Taken together, these results suggest that CqNELF-E plays an antiviral role, probably via inhibition on the viral transcription activity in WSSV infection in a crustacean.

11.
Front Immunol ; 11: 268, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32194551

RESUMO

Phagocytosis is an ancient, highly conserved process in all multicellular organisms, through which the host can protect itself against invading microorganisms and environmental particles, as well as remove self-apoptotic cells/cell debris to maintain tissue homeostasis. In crustacean, phagocytosis by hemocyte has also been well-recognized as a crucial defense mechanism for the host against infectious agents such as bacteria and viruses. In this review, we summarized the current knowledge of hemocyte-mediated phagocytosis, in particular focusing on the related receptors for recognition and internalization of pathogens as well as the downstream signal pathways and intracellular regulators involved in the process of hemocyte phagocytosis. We attempted to gain a deeper understanding of the phagocytic mechanism of different hemocytes and their contribution to the host defense immunity in crustaceans.

12.
Dev Comp Immunol ; 107: 103640, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32078959

RESUMO

In contrast to that hypoacetylation of histones is associated with condensed chromatin and gene silencing, the hyperacetylation of histones can promote an "open chromatin" conformation and transcriptional activation, which is recruited by some viruses to enhance the viral genome replication in host cells. However, the function of histone acetylation modification in the infection of white spot syndrome virus (WSSV), one of the most virulent pathogens for crustaceans like shrimp and crayfish at present, is still unknown. Previously, we found that the transcript of a histone K-Lysine acetyltransferase CqKAT2A-like gene was down-regulated in a differentially expressed transcriptome library of the haematopietic tissue (Hpt) cells from red claw crayfish Cherax quadricarinatus upon WSSV infection at 12 hpi. To further reveal its possible role in anti-WSSV response, CqKAT2A-like gene was then identified with an open reading frame (ORF) of 2523 bp encoding 840 amino acids, which contained a conserved PCAF-N domain, acetyltransf1 domain and bromo domain. Gene expression analysis showed that CqKAT2A-like was distributed in all tissues examined with high presence in haemocyte and muscle, and the transcript was significantly down-regulated after WSSV infection in Hpt cells. Furthermore, the level of histone H3 acetylation (H3ac) was strongly reduced by gene silencing of CqKAT2A-like, which was accompanied with the significantly decreased gene expression of WSSV in Hpt cells, suggesting that CqKAT2A-like gene can promote the activity H3ac and the replication of WSSV. When the H3ac was induced by histone deacetyltransferase inhibitor TSA, the transcription of WSSV genes including both IE1 and VP28 genes was significantly increased, indicating that H3ac participated in WSSV infection in Hpt cells. Taken together, these data suggest that CqKAT2A-like gene might promote the replication of WSSV by regulating H3ac, which sheds new light on the pathogenesis of WSSV in crustaceans.

13.
J Clin Monit Comput ; 2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32088910

RESUMO

The respiration rate (RR) is a vital sign in physiological measurement and clinical diagnosis. RR can be measured using stretchable and wearable strain gauge sensors which detect the respiratory movements in the abdomen or thorax areas caused by volumetric changes. In different body locations, the accuracy of RR detection might differ due to different respiratory movement amplitudes. Few studies have quantitatively investigated the effect of the measurement location on the accuracy of new sensors in RR detection. Using a stretchable and wearable inkjet-printed strain gauge (IPSG) sensor, RR was measured from five body locations (umbilicus, upper abdomen, xiphoid process, upper thorax, and diagonal) on 30 healthy test subjects while sitting on an armless chair. At each location, reference RR was simultaneously detected by the e-Health sensor, and the measurement was repeated twice. Subjects were asked about the comfortableness of locations. Based on Levene's test, ANOVA was performed to investigate if there is a significant difference in RR between sensors, measurement locations, and two repeated measurements. Bland-Altman analysis was applied to the RR measurements at different locations. The effects of measurement site and measurement trials on RR difference between sensors were also investigated. There was no significant difference between IPSG and reference sensors, between any locations, and between the two measurements (all p > 0.05). As to the RR deviation between IPSG and reference sensors, there was no significant difference between any locations, or between two measurements (all p > 0.05). All the 30 subjects agreed that diagonal and upper thorax positions were the most uncomfortable and most comfortable locations for measurement, respectively. The IPSG sensor could accurately detect RR at five different locations with good repeatability. Upper thorax was the most comfortable location.

14.
Artigo em Inglês | MEDLINE | ID: mdl-32097281

RESUMO

Wiskott-Aldrich syndrome (WAS) and osteopetrosis are 2 different, rare hereditary diseases. Here we report clinical and molecular genetics investigations on an infant patient with persistent thrombocytopenia and prolonged fever. He was clinical diagnosed as osteopetrosis according to clinical presentation, radiologic skeletal features, and bone biopsy results. Gene sequencing demonstrated a de novo homozygous mutation in 5'-untranslated region of TNFRSF11A, c.-45A>G, which is relating to osteopetrosis. Meanwhile, a hemizygous transition mutation in WAS gene, c.400G>A diagnosed the infant with WAS. This is the first clinical report for the diagnosis of osteopetrosis coinheritance with WAS in a single patient.

15.
Nature ; 577(7792): 682-688, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31942069

RESUMO

Mycobacterium tuberculosis is an intracellular pathogen that uses several strategies to interfere with the signalling functions of host immune molecules. Many other bacterial pathogens exploit the host ubiquitination system to promote pathogenesis1,2, but whether this same system modulates the ubiquitination of M. tuberculosis proteins is unknown. Here we report that the host E3 ubiquitin ligase ANAPC2-a core subunit of the anaphase-promoting complex/cyclosome-interacts with the mycobacterial protein Rv0222 and promotes the attachment of lysine-11-linked ubiquitin chains to lysine 76 of Rv0222 in order to suppress the expression of proinflammatory cytokines. Inhibition of ANAPC2 by specific short hairpin RNA abolishes the inhibitory effect of Rv0222 on proinflammatory responses. Moreover, mutation of the ubiquitination site on Rv0222 impairs the inhibition of proinflammatory cytokines by Rv0222 and reduces virulence during infection in mice. Mechanistically, lysine-11-linked ubiquitination of Rv0222 by ANAPC2 facilitates the recruitment of the protein tyrosine phosphatase SHP1 to the adaptor protein TRAF6, preventing the lysine-63-linked ubiquitination and activation of TRAF6. Our findings identify a previously unrecognized mechanism that M. tuberculosis uses to suppress host immunity, and provide insights relevant to the development of effective immunomodulators that target M. tuberculosis.


Assuntos
Proteínas de Bactérias/imunologia , Proteínas de Bactérias/metabolismo , Interações Hospedeiro-Patógeno/imunologia , Mycobacterium tuberculosis/imunologia , Tuberculose/imunologia , Ubiquitinação , Ciclossomo-Complexo Promotor de Anáfase/química , Animais , Subunidade Apc2 do Ciclossomo-Complexo Promotor de Anáfase/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Células Cultivadas , Citocinas/antagonistas & inibidores , Citocinas/imunologia , Citocinas/metabolismo , Feminino , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Lisina/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 6/metabolismo , Transdução de Sinais , Fator 6 Associado a Receptor de TNF/antagonistas & inibidores , Fator 6 Associado a Receptor de TNF/metabolismo , Fator de Transcrição AP-1/metabolismo , Tuberculose/microbiologia , Virulência/imunologia
16.
Pharmacotherapy ; 40(1): 4-16, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31742742

RESUMO

BACKGROUND: The pathogenic mechanism of antituberculous drug-induced liver injury (ATDILI) is associated with antioxidant enzymes. The objective of the present study was to investigate the associations of ATDILI susceptibility with genetic polymorphisms of antioxidant enzyme genes including nitric oxide synthase 2 (NOS2), thioredoxin reductase 1 (TXNRD1), superoxide dismutase 2 (SOD2), BTB domain and CNC homolog 1 (BACH1), and MAF bZIP transcription factor K (MAFK). METHODS: Thirty tag single nucleotide polymorphisms (tag-SNPs) from the all candidate genes were genotyped in a 2-stage cohort study including an initial discovery stage with 461 ATDILI patients and 466 controls and a replication stage with 216 ATDILI patients and 432 controls. The frequencies and distributions of genotypes and haplotypes were compared between the case and control groups. Three different genetic models including dominant, recessive, and additive models were used to determine the associations with susceptibility to ATDILI. RESULTS: The SNPs rs9906835, rs944725, and rs3794764 of the NOS2 gene were significantly associated with an increased risk of ATDILI. The MAFK rs3735656 SNP was significantly associated with a decreased risk for ATDILI. The AAA haplotype of the NOS2 gene was associated with susceptibility to ATDILI. The treatment outcomes of patients with tuberculosis were further affected by genetic variants of the NOS2 and MAFK genes. CONCLUSIONS: Genetic polymorphisms of NOS2 and MAFK are associated with ATDILI susceptibility in Chinese patients with tuberculosis. The variants in NOS2 and MAFK affect treatment outcomes of tuberculosis patients. Further studies are needed to better understand the molecular mechanisms of ATDILI susceptibility via regulation of the expression of ATDILI-susceptibility genes and proteins.

17.
Ann Surg Oncol ; 27(5): 1480-1487, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31776702

RESUMO

PURPOSE: This study evaluated the additional value of lymph node ratio (LNR) when used in combination with the 8th American Joint Committee on Cancer (AJCC) staging system for gastric cancer (GC) to establish a new LNR-based AJCC (rAJCC) staging system. METHODS: We searched the Surveillance, Epidemiology, and End Results database to identify patients who had undergone surgery to resect nonmetastatic GC during the period from 2004 to 2013. Recursive partitioning analysis was used to identify the optimal cutoff points for LNR, and an LNR-based N classification system was designed accordingly. The two staging systems were compared in terms of discriminatory ability, as measured by the concordance index. The likelihood ratio Chi square test was used to assess prognostic homogeneity. RESULTS: A total of 13,027 patients were included in the final analysis. All of the included patients, who belonged to the 8th AJCC IIIA category, could be further classified into the rIIB, rIIIA, rIIIB, and rIIIC subgroups using the proposed rAJCC classification system. A difference in 5-year overall survival rate was found between patients classified as having rIIA disease and those classified as having rIIIC disease (66.7% vs. 5.1%). The rAJCC staging system was superior to the 8th AJCC staging system in terms of discriminatory capacity and prognostic homogeneity. CONCLUSIONS: A new rAJCC staging system is proposed, with prognostic superiority to the 8th AJCC staging system for patients with GC. The rAJCC staging system may serve as a useful tool in clinical practice.

18.
J Cereb Blood Flow Metab ; 40(1): 126-134, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30351176

RESUMO

We aimed to investigate the roles of antegrade residual flow and leptomeningeal collateral flow in sustaining cerebral perfusion distal to an intracranial atherosclerotic stenosis (ICAS). Patients with apparently normal cerebral perfusion distal to a symptomatic middle cerebral artery (MCA)-M1 stenosis were enrolled. Computational fluid dynamics models were built based on CT angiography to obtain a translesional pressure ratio (PR) to gauge the residual antegrade flow. Leptomeningeal collaterals (LMCs) were scaled on CT angiography. Cerebral perfusion metrics were obtained in CT perfusion maps. Among 83 patients, linear regression analyses revealed that both translesional PR and LMC scale were independently associated with relative ipsilesional mean transit time (rMTT). Subgroup analyses showed that ipsilesional rMTT was significantly associated with translesional PR (p < 0.001) rather than LMC scale in those with a moderate (50-69%) MCA stenosis, which, however, was only significantly associated with LMC scale (p = 0.051) in those with a severe (70-99%) stenosis. Antegrade residual flow and leptomeningeal collateral flow have complementary effects in sustaining cerebral perfusion distal to an ICAS, while cerebral perfusion may rely more on the collateral circulation in those with a severe stenosis.

20.
Biomed Res Int ; 2019: 3168541, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31737659

RESUMO

Background: Uterine contraction (UC) is the tightening and shortening of the uterine muscles which can indicate the progress of pregnancy towards delivery. Electrohysterogram (EHG), which reflects uterine electrical activities, has recently been studied for UC monitoring. In this paper, we aimed to evaluate different EHG segments for recognizing UCs using the convolutional neural network (CNN). Materials and Methods: In the open-access Icelandic 16-electrode EHG database (122 recordings from 45 pregnant women), 7136 UC and 7136 non-UC EHG segments with the duration of 60 s were manually extracted from 107 recordings of 40 pregnant women to develop a CNN model. A fivefold cross-validation was applied to evaluate the CNN based on sensitivity (SE), specificity (SP), and accuracy (ACC). Then, 1056 UC and 1056 non-UC EHG segments were extracted from the other 15 recordings of 5 pregnant women. Furthermore, the developed CNN model was applied to identify UCs using different EHG segments with the durations of 10 s, 20 s, and 30 s. Results: The CNN achieved the average SE, SP, and ACC of 0.82, 0.93, and 0.88 for a 60 s EHG segment. The EHG segments of 10 s, 20 s, and 30 s around the TOCO peak achieved higher SE and ACC than the other segments with the same duration. The values of SE from 20 s EHG segments around the TOCO peak were higher than those from 10 s to 30 s EHG segments on the same side of the TOCO peak. Conclusion: The proposed method could be used to determine the efficient EHG segments for recognizing UC with the CNN.


Assuntos
Contração Uterina/fisiologia , Útero/fisiologia , Bases de Dados Factuais , Eletrodos , Eletromiografia/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Redes Neurais de Computação , Gravidez , Sensibilidade e Especificidade
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