Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.528
Filtrar
1.
Forensic Sci Int Genet ; 57: 102657, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34973558

RESUMO

In recent years, extraordinary progress has been made in genome sequencing technologies, which has led to a decrease in cost and an increase in the diversity of sequenced genomes. Nanopore sequencing is one of the latest genome sequencing technologies. It aims to sequence longer contiguous pieces of DNA, which are essential for resolving structurally complex regions, and provides a new approach for forensic genetics to detect longer markers in real time. To date, multiple studies have been conducted to sequence forensic markers using MinION from Oxford Nanopore Technologies (ONT), and the results indicate that nanopore sequencing holds promise for forensic applications. Qitan Technology (QitanTech) recently launched its first commercial nanopore genome sequencer, QNome. It could achieve a read length of more than 150 kbp, and could generate approximately 500 Mb of data in 8 h. In this pilot study, we explored and validated this alternative nanopore sequencing device for microhaplotype (MH) profiling using a custom set of 15 MH loci. Seventy single-contributor samples were divided into 7 batches, each of which included 10 samples and control DNA 9947A and was sequenced by QNome. MH genotypes generated from QNome were compared to those from Ion Torrent sequencing (Ion S5XL system) to evaluate the accuracy and stability. Twelve samples randomly selected from the last three batches and Control DNA 9947A were also subjected to ONT MinION sequencing (with R9.4 flow cell) for parallel comparison. Based on MHtyper, a bioinformatics workflow developed for automated MH designation, all MH loci can be genotyped and reliably phased using the QNome data, with an overall accuracy of 99.83% (4 errors among 2310 genotypes). Three occurred near or in the region of homopolymer sequences, and one existed within 50 bp of the start of the sequencing reaction. In the last 15 samples (12 individual samples and 3 replicates of control DNA 9947A), two SNPs located at 4-mer homopolymers failed to obtain reliable genotypes on the MinION data. This study shows the potential of state-of-the-art nanopore sequencing methods to analyze forensic MH markers. Given the rapid pace of change, sporadic and nonrepetitive errors presented in this study are expected to be resolved by further developments of nanopore technologies and analysis tools.


Assuntos
Sequenciamento por Nanoporos , Nanoporos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Projetos Piloto , Análise de Sequência de DNA/métodos
2.
ACS Omega ; 7(35): 31538-31543, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36092553

RESUMO

Diamond samples of defects with negatively charged nitrogen-vacancy (NV) centers are promising solid-state spin sensors suitable for quantum information processing and highly sensitive measurements of magnetic, electric, and thermal fields at the nanoscale. A diamond defect with an NV center is unique for its robust temperature-dependent zero-field splitting D gs of the triplet ground state. This property enables the optical readout of electron spin states through manipulation of the ground triplet state using microwave resonance with D gs from 100 K to approximately 600 K. Thus, prohibiting D gs from external thermal disturbances is crucial for an accurate measurement using NV-diamond sensors. Nevertheless, the external microwave field probably exerts a heating effect on the diamond sample of NV centers. To our knowledge, the microwave heating effect on the diamond samples of NV centers has yet to be quantitatively and systematically addressed. Our observation demonstrates the existence of a prominent microwave heating effect on the diamond samples of NV centers with the microwave irradiation in a continuous mode and some pulse sequence modes. The zero-field splitting D gs is largely red-shifted by the temperature rises of the diamond samples. The effect will inevitably cause NV-diamond sensors to misread the true temperature of the target and disturb magnetic field detection by perturbing the spin precession of NV centers. Our observation demonstrates that such a phenomenon is negligible for the quantum lock-in XY8-N method.

3.
Front Cardiovasc Med ; 9: 841453, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36093135

RESUMO

Background: Sit-To-Stand (STS) tests are reported as feasible alternatives for the assessment of functional fitness but the reliability of these tests in people with coronary artery disease (CAD) has not been reported. This study explored the test-retest reliability, convergent and known-groups validity of the five times, 30-sec and 1-min sit-to-stand test (FTSTS test, 30-s STS test and 1-min STS test respectively) in patients with CAD. The feasibility of applying these tests to distinguish the level of risk for cardiovascular events in CAD patients was also investigated. Methods: Patients with stable CAD performed a 6MWT and 3 STS tests in random order on the same day. Receiver operating characteristic (ROC) curve analyses were conducted using STS test data to differentiate patients with low or high risk of cardiovascular events based on the risk level determined by distance covered in the 6MWT as > or ≤ 419 m. Thirty patients repeated the 3 STS tests on the following day. Results: 112 subjects with diagnoses of atherosclerosis or post-percutaneous coronary intervention, or post-acute myocardial infarction (post-AMI) participated in the validity analysis. All 3 STS tests demonstrated moderate and significant correlation with the 6MWT (coefficient values r for the FTSTS, 30-s STS and 1-min STS tests were-0.53, 0.57 and 0.55 respectively). Correlations between left ventricular ejection fraction (LVEF) and all STS tests and between 6MWT and LVEF were only weak (r values ranged from 0.27 to 0.31). Subgroup analysis showed participants in the post-AMI group performed worse in all tests compared to non-myocardial infarction (non-MI) group. The area under the curve (AUC) was 0.80 for FTSTS (sensitivity: 75.0%, specificity: 73.8%, optimal cut-off: >11.7 sec), and the AUC, sensitivity, specificity and optimal cut-off for 30-s STS and 1-min STS test were 0.83, 75.0%, 76.2%, ≤ 12 repetitions and 0.80, 71.4%, 73.8%, ≤ 23 repetitions respectively. The intraclass correlation coefficients (ICC) for repeated measurements of the FTSTS, 30-s STS and 1-min STS tests were 0.96, 0.95 and 0.96 respectively, with the minimal detectable change (MDC95) computed to be 1.1 sec 1.8 repetitions and 3.9 repetitions respectively. Conclusions: All STS tests demonstrated good test-retest reliability, convergent and known-groups validity. STS tests may discriminate low from high levels of risk for a cardiovascular event in patients with CAD.

4.
J Clin Pharmacol ; 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36097320

RESUMO

This study aimed to develop and evaluate a population pharmacokinetic (PPK) combined machine learning approach to predict tacrolimus trough concentrations for Chinese adult liver transplant recipients in the early post-transplant period. Tacrolimus trough concentrations were retrospectively collected from routine monitoring records of liver transplant recipients and divided into the training dataset (1287 concentrations in 145 recipients) and the test dataset (296 concentrations in 36 recipients). A PPK model was first established using NONMEM. Then a machine learning model of Xgboost was adapted to fit the estimated individual pharmacokinetic parameters obtained from the PPK model with Bayesian forecasting. The performance of the final PPK model and Xgboost model was compared in the test dataset. In the final PPK model, tacrolimus daily dose, postoperative days, hematocrit, aspartate aminotransferase, and concomitant with voriconazole were identified to significantly influence the clearance. The postoperative days along with hematocrit significantly influence the volume of distribution. In the Xgboost model, the first five predictors for predicting the clearance were concomitant with voriconazole, sex, SNPs of CYP3A4*1G and CYP3A5*3 in recipients, and tacrolimus daily dose, for the volume of distribution were postoperative days, age, weight, total bilirubin and Graft: recipient weight ratio. In the test dataset, the Xgboost model showed the minimum median prediction error of tacrolimus concentrations than the PPK model with or without Bayesian forecasting. In conclusion, a PPK combined machine learning approach could improve the prediction of tacrolimus concentrations for Chinese adult liver transplant recipients in the early post-transplant period. This article is protected by copyright. All rights reserved.

5.
Animal Model Exp Med ; 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36097701

RESUMO

BACKGROUND: SHARPIN (SHANK-associated RH domain interactor) is a component of the linear ubiquitination complex that regulates the NF-κB signaling pathway. To better understand the function of SHARPIN, we sought to establish a novel genetically engineered Syrian hamster with SHARPIN disruption using the CRISPR/Cas9 system. METHODS: A single-guide ribonucleic acid targeting exon 1 of SHARPIN gene was designed and constructed. The zygotes generated by cytoplasmic injection of the Cas9/gRNA ribonucleoprotein were transferred into pseudopregnant hamsters. Neonatal mutants were identified by genotyping. SHARPIN protein expression was detected using Western blotting assay. Splenic, mesenteric lymph nodes (MLNs), and thymic weights were measured, and organ coefficients were calculated. Histopathological examination of the spleen, liver, lung, small intestine, and esophagus was performed independently by a pathologist. The expression of lymphocytic markers and cytokines was evaluated using reverse transcriptase-quantitative polymerase chain reaction. RESULTS: All the offspring harbored germline-transmitted SHARPIN mutations. Compared with wild-type hamsters, SHARPIN protein was undetectable in SHARPIN-/- hamsters. Spleen enlargement and splenic coefficient elevation were spotted in SHARPIN-/- hamsters, with the descent of MLNs and thymuses. Further, eosinophil infiltration and structural alteration in spleens, livers, lungs, small intestines, and esophagi were obvious after the deletion of SHARPIN. Notably, the expression of CD94 and CD22 was downregulated in the spleens of knockout (KO) animals. Nonetheless, the expression of CCR3, CCL11, Il4, and Il13 was upregulated in the esophagi. The expression of NF-κB and phosphorylation of NF-κB and IκB protein significantly diminished in SHARPIN-/- animals. CONCLUSIONS: A novel SHARPIN KO hamster was successfully established using the CRISPR/Cas9 system. Abnormal development of secondary lymphoid organs and eosinophil infiltration in multiple organs reveal its potential in delineating SHARPIN function and chronic inflammation.

6.
J Contam Hydrol ; 251: 104069, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36095968

RESUMO

There has been an increase in marine transportation in cold regions, which in turn has led to an increasing risk of oil spills in these areas. To better support risk assessment and pollution control of oil spills, it is important to have a good understanding of oil transport in the environment. This information is essential to manage response priorities and help prepare contingency and mitigating measures. This study aims to simulate 3D wave propagation in shallow water with different broken-ice aerial coverage percentages to assess the fate and transport of oil spill in a nearshore area under different conditions. Based on the Reynolds-averaged Navier-Stokes momentum equations for an incompressible viscous fluid and the Volume of Fluid (VOF) method that is coupled with Six Degree of Freedom (6-DOF) model, a 3D numerical model of three-phase transient flow was developed. It was found that the presence of ice makes the spreading of spilled oil slower in the horizontal direction since the ice can build natural barriers to oil movement. The higher the ice concentration, the slower spilled oil migrates in all directions. The maximum oil volume fraction varies with increasing ice coverage on the water surface area. The wave frequency, the averaged flow velocity, and oil properties affect the oil spread extent and the oil volume fraction. The dumping effect of the wave due to the presence of ice makes the impact of this factor less critical than those in open water.

7.
J Adv Res ; 40: 249-261, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36100330

RESUMO

INTRODUCTION: Adriamycin (ADR) is an efficient and common broad-spectrum anticancer drug. However, the cumulative and dose-dependent toxicity induced by ADR severely limits its application in the clinic. Previous studies found that psoralidin (PSO) exhibits remarkable therapeutic effects against multiple cancers. OBJECTIVES: The aim of this study was to determine if PSO has beneficial effects on ADR-induced cardiotoxicity and to investigate the underlying mechanisms. METHODS: ADR-induced cardiotoxicity models were established in BALB/c mice and HL-1 cardiomyocytes. A series of experimental methods were used to evaluate the effects of PSO on cardiac function indicators, blood biochemical parameters, histopathology, oxidative stress, apoptosis, mitochondrial function, fibrosis, and SIRT1/PPARγ signaling. RESULTS: PSO significantly improved cardiac function indicators, blood biochemical parameters, and mitochondrial function and reduced the degree of myocardial fibrosis, oxidative stress, and apoptosis in ADR-injured mice. PSO significantly increased cell viability, inhibited the release of LDH, reduced oxidative stress and apoptosis, and improved mitochondrial function in ADR-injured HL-1 cells. Moreover, we also demonstrated there was cross-talk between SIRT1 and PPARγ, as shown by SIRT1 siRNA significantly decreasing the expression of PPARγ and GW9662 (a PPARγ antagonist), which remarkably reduced the expression of SIRT1. CONCLUSION: In summary, this study proved for the first time the beneficial effect of PSO on ADR-induced cardiotoxicity through activation of the SIRT1/PPARγ signaling pathway. Therefore, these findings may favor PSO as a potential cardioprotective drug candidate to alleviate ADR-induced cardiotoxicity in the clinic and improve the application of ADR in oncotherapy.


Assuntos
Cardiotoxicidade , Doxorrubicina , Animais , Benzofuranos , Cardiotoxicidade/tratamento farmacológico , Cumarínicos , Doxorrubicina/efeitos adversos , Camundongos , PPAR gama , Sirtuína 1/metabolismo
8.
Water Res ; 224: 119068, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36103780

RESUMO

Plutonium (Pu) in the subsurface environment can transport in different oxidation states as an aqueous solute or as colloidal particles. The transport behavior of Pu is affected by the relative abundances of these species and can be difficult to predict when they simultaneously exist. This study investigates the concurrent transport of Pu intrinsic colloids, Pu(IV)(aq) and Pu(V-VI)(aq) through a combination of controlled experiments and semi-analytical dual-porosity transport modeling. Pu transport experiments were conducted in a fractured granite at high and low flow rates to elucidate sorption processes and their scaling behavior. In the experiments, Pu(IV)(aq) was the least mobile of the Pu species, Pu(V-VI)(aq) had intermediate mobility, and the colloidal Pu, which consisted mainly of precipitated and/or hydrolyzed Pu(IV), was the most mobile. The semi-analytical modeling revealed that the sorption of each Pu species was rate-limited, as the sorption could not be described by assuming local equilibrium in the experiments. The model was able to describe the sorption of the different Pu species that occurring either on fracture surfaces, in the pores of the rock matrix, or simultaneously in both locations. While equally good fits to the data could be achieved using any of these assumptions, a fracture-dominated process was considered to be the most plausible because it provided the most reasonable estimates of sorption rate constants. Importantly, a key result of this work is that the sorption rate constant of all Pu species tends to decrease with increasing time scales, which implies that Pu will tend to be more mobile at longer time scales than observations at shorter time scales suggest. This result has important implications for predicting the environmental impacts of Pu in the safety assessments of geologic repositories for radioactive waste disposal, and we explore potential mechanistic bases for upscaling the sorption rate constants to time and distance scales that cannot be practically evaluated in experiments.

9.
Am J Surg ; 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36116972

RESUMO

BACKGROUND: This study investigated the association between different risk levels of de novo donor-specific anti-human leukocyte antigen antibodies (dnDSAs) and liver graft injury after liver transplantation in pediatric patients. METHODS: This retrospective cohort study enrolled 130 patients after liver transplantation. Subjects were divided into the following 4 groups according to the mean fluorescence intensity (MFI) of dnDSAs: high risk group(MFI ≥10,000), medium risk group(4000 ≤ MFI <10,000), low risk group(500 ≤ MFI <4000), and negative group(<500). Liver function indices were examined along with liver puncture biopsy,and the relationship between dnDSA risk level and liver injury after transplantation was assessed. RESULTS: Pediatric liver transplant recipients showed significant differences in liver function (ALT, AST, GGT and Bilirubin) according to dnDSA risk level (P < 0.05), and no differences in cumulative incidences of rejection (P = 0.413) and liver fibrosis (P = 0.978) were observed among the number of dnDSAs group. There were differences in the cumulative incidences of antibody-mediated rejection (AMR) (P = 0.001) and T cell-mediated rejection (TCMR) (P = 0.003) across risk groups. The cumulative incidences of TCMR and liver fibrosis (P = 0.0001) were higher in the low-risk group than in the other 3 groups. There were no differences in graft survival rate (P = 0.846) across risk groups. CONCLUSION: DnDSAs in pediatric liver transplant recipients are associated with liver transplant rejection and fibrosis. The level of dnDSAs in low risk group should not be disregarded. Routine detection of dnDSAs has clinical utility for noninvasive risk stratification in this population.

11.
J Phys Chem B ; 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36129778

RESUMO

Viscoelastic characterization is of great importance for the investigation of biomolecular condensates. Single-particle-tracking-based rotational diffusion analysis of single nanorods is an effective approach for quantitative viscosity measurement. However, in the case of high background and noise with high-speed image acquisition, accurate extraction of diffusivity from the data is a challenging task. Here, we develop a novel frequency-domain-based deep learning (DL) method for single nanorod rotational tracking analysis. We synthesized Brownian rotational time-series data for training, designed a data preprocessing module to reduce the effect of noise, and extracted rotational diffusion coefficient using recurrent neural networks in the frequency domain. Compared with the traditional curve-fitting-based methods, our method shows higher accuracy and a wider detection range for viscosity measurement. We verified our method using experimental data from plasmonic imaging of single gold nanorods (AuNRs) in glycerol solution and PGL droplets. Our method can be potentially applied to the viscosity measurement of different biomolecular condensates in vitro and in vivo.

12.
Inorg Chem ; 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36122376

RESUMO

The electrocatalytic nitrate reduction reaction (NO3--ERR) to ammonia (NH3) is a promising strategy for NH3 production. Cu-based nanomaterials have been regarded as a kind of effective NO3--ERR catalysts. In this work, high-quality hollow Cu2O nanocubes (Cu2O h-NCs) are facilely synthesized by a simple one-step reduction method. The as-prepared Cu2O h-NCs reveal high selectivity and activity for NO3--ERR, which is ascribed to abundant oxygen vacancies, high surface area, hollow architecture, low mass transfer resistance, and strong adsorbing ability toward NO3-. In fact, Cu2O h-NCs can achieve a Faradic efficiency of 92.9% and an NH3 yield of 56.2 mg h-1 mgcat-1 for NH3 production at -0.85 V (vs RHE) potential, which exceeds those of other transition-metal-based NO3--ERR electrocatalysts.

13.
J Cosmet Dermatol ; 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36065721

RESUMO

BACKGROUND: Currently, most studies of ELAV (Embryonic Lethal, Abnormal Vision, Drosophila)-like protein 4 (Hu antigen D, HuD) focus on nervous system-related diseases; the role of HuD in the occurrence of skin aging and seborrheic keratosis (SK) has not been reported. OBJECTIVE: To explore the role of HuD in the occurrence of SK and skin aging and its related clinical significance. METHODS: The expression levels of HuD in the skin and blood of healthy people at different ages, SK lesions, and perilesional skin of SK patients were detected by both immunohistochemistry and Western blotting. The mRNA expression levels of HuD in the skin and blood of healthy peoples at different ages were detected by quantitative real-time reverse transcription-polymerase chain reaction. The expression level of HuD was compared with the skin of healthy people, SK lesion, and perilesional skin of SK patients of the same age. RESULTS: The immunohistochemistry and Western blotting showed that the expression levels of HuD in SK lesions were higher than those in healthy skin and perilesional skin. The immunohistochemical staining intensity, protein and mRNA expression levels of HuD in the skin and blood of healthy people were correlated with age, which gradually increased with increasing age. CONCLUSION: HuD is highly expressed in SK lesion and aged skin, indicating that a higher HuD expression level is correlated with occurrence of SK and aging skin; however, its mechanism needs to be further studied.

14.
Cancer Biol Ther ; 23(1): 336-347, 2022 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-36112948

RESUMO

Melanoma is a highly aggressive cancer that can metastasize at early stage. The aim of this study is to clarify the role of Piezo1 and its potential mechanism in regulating the malignant phenotypes of melanoma. In the present study, we first showed that Piezo1 was abnormally expressed in melanoma, which accelerated the malignant progression by activating AKT/mTOR signaling. Firstly, we found that Piezo1 was upregulated in melanoma and associated with poor survival. Additionally, Piezo1 knockdown significantly weakened intracellular calcium signal and viability of melanoma cells. Furthermore, Piezo1 knockdown inhibited the transendothelial migration and invasion in vitro, as well as metastasis in vivo. Mechanistically, we found that Piezo1 activated AKT/mTOR signaling to maintain malignant phenotypes of melanoma. Therefore, Piezo1 acts as an oncogene in melanoma cells and provides a novel candidate for melanoma diagnosis and treatment.


Assuntos
Melanoma , Proteínas Proto-Oncogênicas c-akt , Cálcio , Humanos , Canais Iônicos/genética , Melanoma/genética , Melanoma/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
15.
Fertil Steril ; 118(3): 456-462, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36116799

RESUMO

It is well documented that obesity decreases natural fertility among men and women as well as pregnancy chances after conventional infertility and assisted reproductive technology (ART)-based treatments. Moreover, pregnancy complications are increased in women with overweight and obesity. General guidelines on the treatment of obesity recommend lifestyle intervention, including diet and exercise as the first-line treatment, coupled with or without medical treatments, such as weight loss medication or bariatric surgery, to reduce complications of obesity in adults. In the context of infertility in various countries and infertility clinics, there is a body mass index limit for public refund of infertility treatment of women with obesity. In this respect, it is important to investigate the evidence of effects of lifestyle intervention preceding infertility treatment on reproductive outcomes. The combined results of 15 randomized controlled trials (RCTs) of the effectiveness of preconception lifestyle intervention on reproductive outcomes documented in the latest systemic review and meta-analysis, together with the most recent RCT performed in 2022 are discussed. The current evidence suggests that greater weight loss and increase in clinical pregnancy, live birth, and natural conception rates after lifestyle intervention compared with no intervention were observed, but it seems no beneficial effect of lifestyle intervention preceding ART was observed on these parameters. With respect to potential harm of lifestyle intervention, there is no significant increased risk of early pregnancy loss, although the most recent RCT (not included in the systematic review and meta-analysis) showed a trend toward an increased risk. Complications during pregnancy, such as early pregnancy loss and maternal as well as fetal and neonatal complications, are underreported in most studies and need further analysis in an individual participant data meta-analysis. Limitations of the studies as well as future perspectives and challenges in this field of research will be highlighted.


Assuntos
Aborto Espontâneo , Infertilidade , Complicações na Gravidez , Adulto , Feminino , Fertilidade , Humanos , Recém-Nascido , Infertilidade/complicações , Infertilidade/diagnóstico , Infertilidade/terapia , Estilo de Vida , Masculino , Obesidade/complicações , Obesidade/diagnóstico , Obesidade/terapia , Gravidez , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/etiologia , Complicações na Gravidez/terapia , Redução de Peso
16.
Angew Chem Int Ed Engl ; : e202211356, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36055964

RESUMO

By designing a tetraphenylethylene (TPE)-based AIEgen-ligand with reduced symmetry, we obtained two alkaline-earth metal-based MOFs (LIFM-102 and LIFM-103) with dense packing structures and low porosity as proved by single-crystal X-ray diffraction and CO2 sorption data. Excitingly, the desolvated MOFs with rigid environment and reduced lattice free solvent exhibit high quantum yields (QY, 64.9 % and 79.4 %) and excellent two-photon excited photoluminescence (TPA cross-sections, 2946.6 GM and 2899.0 GM), while maintaining the external-stimuli-responsive properties suitable for anticounterfeit fields. The effect of ligand conformation was validated by comparing the structure and fluorescence properties of the samples before and after desolvation and further verified by theoretical calculations. This work expands the study on TPE-cored materials to symmetry-reduced ligand and might bring forward novel structures and excellent photoluminescent properties in the future.

17.
Front Genet ; 13: 900495, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105106

RESUMO

Background: The SERPINH1 gene plays a vital part in tumorigenesis and development, whereas its potential as an immunotherapy target is still unknown. Hence, this research aimed to probe the roles of SERPINH1 in human tumors. Method: Using The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) database, Oncomine, and SangerBox software, the pan-cancer expression of SERPINH1 and its correlation were systematically analyzed. SERPINH1 protein information was detected by the Human Protein Atlas (HPA) database and STRING database. The genomic alterations of SERPINH1 were studied using the c-BioPortal database. The influence of SERPINH1 on prognosis was analyzed using Kaplan-Meier plotter. The R package "clusterProfiler" was used for enrichment analysis to detect the role of SERPINH1. The TIMER2 database was used to further analyze the correlation between the immune cell infiltration score of TCGA samples and the expression of SERPINH1. Results: SERPINH1 overexpression was related to worse survival status in pan-cancer. In addition, high expression of SERPINH1 was positively associated with tumor stage and poor prognosis. Moreover, SERPINH1 played an important role in tumor microenvironment and immune regulation. Our study revealed that SERPINH1 expression has a strong correlation with immune cell filtration, immune regulation, chemokines, and immune checkpoints. Conclusion: Our research found that SERPINH1 was a risk factor and predictor of poor prognosis in various tumors. High expression of SERPINH1 may contribute to tumor immune-suppressive status. Also, SERPINH1 may become a potential immunotherapy target in pan-cancer.

18.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 47(8): 1037-1048, 2022 Aug 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-36097771

RESUMO

OBJECTIVES: Chronic suppurative otitis media (CSOM) and middle ear cholesteatoma (MEC) are the 2 most common chronic middle ear diseases. In the process of diagnosis and treatment, the 2 diseases are prone to misdiagnosis and missed diagnosis due to their similar clinical manifestations. High resolution computed tomography (HRCT) can clearly display the fine anatomical structure of the temporal bone, accurately reflect the middle ear lesions and the extent of the lesions, and has advantages in the differential diagnosis of chronic middle ear diseases. This study aims to develop a deep learning model for automatic information extraction and classification diagnosis of chronic middle ear diseases based on temporal bone HRCT image data to improve the classification and diagnosis efficiency of chronic middle ear diseases in clinical practice and reduce the occurrence of missed diagnosis and misdiagnosis. METHODS: The clinical records and temporal bone HRCT imaging data for patients with chronic middle ear diseases hospitalized in the Department of Otorhinolaryngology, Xiangya Hospital from January 2018 to October 2020 were retrospectively collected. The patient's medical records were independently reviewed by 2 experienced otorhinolaryngologist and the final diagnosis was reached a consensus. A total of 499 patients (998 ears) were enrolled in this study. The 998 ears were divided into 3 groups: an MEC group (108 ears), a CSOM group (622 ears), and a normal group (268 ears). The Gaussian noise with different variances was used to amplify the samples of the dataset to offset the imbalance in the number of samples between groups. The sample size of the amplified experimental dataset was 1 806 ears. In the study, 75% (1 355) samples were randomly selected for training, 10% (180) samples for validation, and the remaining 15% (271) samples for testing and evaluating the model performance. The overall design for the model was a serial structure, and the deep learning model with 3 different functions was set up. The first model was the regional recommendation network algorithm, which searched the middle ear image from the whole HRCT image, and then cut and saved the image. The second model was image contrast convolutional neural network (CNN) based on twin network structure, which searched the images matching the key layers of HRCT images from the cut images, and constructed 3D data blocks. The third model was based on 3D-CNN operation, which was used for the final classification and diagnosis of the 3D data block construction, and gave the final prediction probability. RESULTS: The special level search network based on twin network structure showed an average AUC of 0.939 on 10 special levels. The overall accuracy of the classification network based on 3D-CNN was 96.5%, the overall recall rate was 96.4%, and the average AUC under the 3 classifications was 0.983. The recall rates of CSOM cases and MEC cases were 93.7% and 97.4%, respectively. In the subsequent comparison experiments, the average accuracy of some classical CNN was 79.3%, and the average recall rate was 87.6%. The precision rate and the recall rate of the deep learning network constructed in this study were about 17.2% and 8.8% higher than those of the common CNN. CONCLUSIONS: The deep learning network model proposed in this study can automatically extract 3D data blocks containing middle ear features from the HRCT image data of patients' temporal bone, which can reduce the overall size of the data while preserve the relationship between corresponding images, and further use 3D-CNN for classification and diagnosis of CSOM and MEC. The design of this model is well fitting to the continuous characteristics of HRCT data, and the experimental results show high precision and adaptability, which is better than the current common CNN methods.


Assuntos
Otopatias , Redes Neurais de Computação , Algoritmos , Humanos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
19.
Cancer Cytopathol ; 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36103360

RESUMO

BACKGROUND: Sputum cell-free DNA (cfDNA) has been confirmed to be a valued surrogate sample for detection of EGFR mutations in patients with lung adenocarcinoma (LAC). Whether it is suitable for detection of mutations of multiple driver genes has not been reported. METHODS: A total of 83 patients with LAC were enrolled and their sputum and paired tumor samples were collected. A next-generation sequencing (NGS)-based 10-gene panel was used to test sputum supernatant-derived cfDNA and paired tumor DNA. The sputum sediments were used for cytological evaluation. RESULTS: The total positive rates of hotspot mutations of the 10 driver genes in sputum cfDNA and matched tissue samples were 65.1% and 77.1%, respectively. The overall detection sensitivity of variants in sputum cfDNA was 81.3% (95% confidence interval [CI], 69.2%, 89.5%) and the specificity was 100% (95% CI, 79.1%, 100%). The sensitivities of testing sputum cfDNA from patients with stage IIIB-IV was 87.0% (95% CI, 74.5%, 94.1%); the sensitivities of testing sputum cfDNA from patients with malignant sputum was 92.3% (95% CI, 78.0%, 98.0%); and the sensitivity of testing sputum cfDNA from patients with malignant sputum in stage IIIB-IV were 94.1% (95% CI, 78.9%, 99.0%). CONCLUSIONS: This study demonstrated that sputum cfDNA were successfully used for the detection of multiple driver genes by NGS. Sputum cfDNA could be a valuable surrogate clinical sample for all-in-one test of mutations to guide target therapies, especially for patients with advanced LAC and malignant sputum.

20.
Artigo em Inglês | MEDLINE | ID: mdl-36107894

RESUMO

Linear discriminant analysis (LDA) is one of the most effective and popular methods to reduce the dimensionality of data with Gaussian assumption. However, LDA cannot handle non-Gaussian data because the center point is incompetent to represent the distribution of data. Some existing methods based on graph embedding focus on exploring local structures via pairwise relationships of data for addressing the non-Gaussian issue. Due to massive pairwise relationships, the computational complexity is high as well as the locally optimal solution is hard to find. To address these issues, we propose a novel and efficient local embedding learning via landmark-based dynamic connections (LDC) in which we leverage several landmarks to represent different subclusters in the same class and establish the connections between each point and landmark. Furthermore, in order to explore the relationship of landmarks pairwise more precisely, the relationship between each point and their corresponding neighbor landmarks are found in the optimal subspace, rather than the original space, which can avoid the negative influence of the noises. We also propose an efficient iterative algorithm to deal with the proposed ratio minimization problem. Extensive experiments conducted on several real-world datasets have demonstrated the advantages of the proposed method.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...