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Cellular reprogramming can manipulate the identity of cells to generate the desired cell types1-3. The use of cell intrinsic components, including oocyte cytoplasm and transcription factors, can enforce somatic cell reprogramming to pluripotent stem cells4-7. By contrast, chemical stimulation by exposure to small molecules offers an alternative approach that can manipulate cell fate in a simple and highly controllable manner8-10. However, human somatic cells are refractory to chemical stimulation owing to their stable epigenome2,11,12 and reduced plasticity13,14; it is therefore challenging to induce human pluripotent stem cells by chemical reprogramming. Here we demonstrate, by creating an intermediate plastic state, the chemical reprogramming of human somatic cells to human chemically induced pluripotent stem cells that exhibit key features of embryonic stem cells. The whole chemical reprogramming trajectory analysis delineated the induction of the intermediate plastic state at the early stage, during which chemical-induced dedifferentiation occurred, and this process was similar to the dedifferentiation process that occurs in axolotl limb regeneration. Moreover, we identified the JNK pathway as a major barrier to chemical reprogramming, the inhibition of which was indispensable for inducing cell plasticity and a regeneration-like program by suppressing pro-inflammatory pathways. Our chemical approach provides a platform for the generation and application of human pluripotent stem cells in biomedicine. This study lays foundations for developing regenerative therapeutic strategies that use well-defined chemicals to change cell fates in humans.
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Diferenciação Celular , Reprogramação Celular , Células-Tronco Pluripotentes Induzidas , Linhagem da Célula , Humanos , Células-Tronco Pluripotentes Induzidas/citologiaRESUMO
A single-fiber photoacoustic (PA) sensor with a silicon cantilever beam for trace acetylene (C2H2) gas analysis was proposed. The miniature gas sensor mainly consisted of a microcantilever and a non-resonant PA cell for the real-time detection of acetylene gas. The gas diffused into the photoacoustic cell through the silicon cantilever beam gap. The volume of the PA cell in the sensor was about 14 µL. By using a 1 × 2 fiber optical coupler, a 1532.8 nm distributed feedback (DFB) laser and a white light interference demodulation module were connected to the single-fiber photoacoustic sensor. A silicon cantilever was utilized to improve the performance when detecting the PA signal. To eliminate the interference of the laser-reflected light, a part of the Fabry-Perot (F-P) interference spectrum was used for phase demodulation to achieve the highly sensitive detection of acetylene gas. The minimum detection limit (MDL) achieved was 0.2 ppm with 100 s averaging time. In addition, the calculated normalized noise equivalent absorption (NNEA) coefficient was 4.4 × 10-9 W·cm-1·Hz-1/2. The single-fiber photoacoustic sensor designed has great application prospects in the early warning of transformer faults.
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OBJECTIVE: To determine whether RAL affects perioperative outcomes and long-term efficacy in NSCLC patients, compared with traditional VAL. SUMMARY OF BACKGROUND DATA: RAL is a promising treatment for NSCLC. However, its efficacy has not been fully evaluated. METHODS: A single-center, open-labeled prospective randomized clinical trial was launched in May 2017 to compare the efficacy of RAL and VAL. By May 2020, 320 patients were enrolled. The perioperative results of RAL and VAL were compared. RESULTS: The 320 enrolled patients were randomly assigned to the RAL group (n = 157) and the VAL group (n = 163). Perioperative outcomes were comparable between the 2 groups, including the length of hospital stay (P = 0.76) and the rate of postoperative complications (P = 0.45). No perioperative mortality occurred in either group. The total amount of chest tube drainage {830âmL [interquartile range (IQR), 550-1130 mL] vs 685âmL [IQR, 367.5-1160 mL], P = 0.007} and hospitalization costs [$12821 (IQR, $12145-$13924) vs $8009 (IQR, $7014-$9003), P < 0.001] were significantly higher in the RAL group. RAL group had a significantly higher number of LNs harvested [11 (IQR, 8-15) vs 10 (IQR, 8-13), P = 0.02], higher number of N1 LNs [6 (IQR, 4-8) vs 5 (IQR, 3-7), P = 0.005], and more LN stations examined [6 (IQR, 5-7) vs 5 (IQR, 4-6), P < 0.001]. CONCLUSIONS: Both RAL and VAL are safe and feasible for the treatment of NSCLC. RAL achieved similar perioperative outcomes, together with higher LN yield. Further follow-up investigations are required to evaluate the long-term efficacy of RAL. (ClinicalTrials.gov identifier: NCT03134534).
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Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Pneumonectomia/métodos , Procedimentos Cirúrgicos Robóticos , Cirurgia Torácica Vídeoassistida , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
In recent years, with the popularity of computed tomography (CT) scanning, early lung cancer has been found in a large number of patients, and segmentectomy has been widely used in clinical practice. The development of intersegmental plane is the most critical step in segmentectomy. At present, there are many methods to identify the intersegmental plane. Also, dissection of the intersegmental plane has been a challenge for thoracic surgeons for decades because of the complicated anatomic variations. This study focuses on the safety and efficacy of relevant methods in both identification and dissection of the intersegmental plane in segmentectomy.
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Neoplasias Pulmonares , Pneumonectomia , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Pneumonectomia/efeitos adversos , Pneumonectomia/métodos , Resultado do TratamentoRESUMO
PURPOSE: The purpose of the study was to evaluate the diagnostic significance of two new and a few clinical markers for prostate cancer (PCa) at various prostate volumes (PV). METHODS: The study subjects were divided into two groups. Among them, there were 70 cases in the PV ≤30 ml group (benign prostatic hyperplasia [BPH]: 32 cases, PCa: 38 cases) and 372 cases in the PV > 30 ml group (BPH: 277 cases, PCa: 95 cases). SPSS 26.0 and GraphPad Prism 8.0 were used to construct their receiver operating characteristic (ROC) curves for diagnosing PCa and calculating their area under the ROC curve (AUC). RESULTS: In the PV ≤30 ml group, the diagnostic parameters based on prostate-specific antigen (PSA) had a decreased diagnostic significance for PCa. In the PV > 30 ml group, PSAD (AUC = 0.709), AVR (AVR = Age/PV, AUC = 0.742), and A-PSAD (A-PSAD = Age×PSA/PV, AUC = 0.736) exhibited moderate diagnostic significance for PCa, which was better than PSA-AV (AUC = 0.672), free PSA (FPSA, AUC = 0.509), total PSA (TPSA, AUC = 0.563), (F/T) PSA (AUC = 0.540), and (F/T)/PSAD (AUC = 0.663). Compared with AVR, A-PSAD exhibited similar diagnostic significance for PCa, but higher than PSA density (PSAD). CONCLUSIONS: Choosing appropriate indicators for different PVs could contribute to the early screening and diagnosis of PCa. The difference in the diagnostic value of two new indicators (A-PSAD and AVR), and PSAD for PCa may require further validation by increasing the sample size.
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Hiperplasia Prostática , Neoplasias da Próstata , Biomarcadores , Detecção Precoce de Câncer , Humanos , Masculino , Próstata/diagnóstico por imagem , Antígeno Prostático Específico , Hiperplasia Prostática/diagnóstico , Neoplasias da Próstata/diagnóstico , Curva ROCRESUMO
This study aimed to analyse the clinical characteristics and risk factors of patients with positive prostate biopsy at 4-20 ng/mL of prostate-specific antigen (PSA), construct a new parameter based on this characteristics and assess its diagnostic value for prostate cancer (PCa). Logistic regression analysis was used to clarify the risk factors of PCa, and a new parameter based on the results was constructed. Compare the diagnostic value of various diagnostic parameters for PCa. Logistic multivariate regression analysis revealed that age (OR, 5.269; 95%CI, 2.762-10.050), comorbid diabetes (OR, 2.437; 95%CI, 1.162-5.111), PSA (OR, 2.462; 95%CI, 1.198-5.059) and prostate volume (PV) (OR, 0.227; 95%CI, 0.100-0.516) are risk factors for PCa. The age, PSA and PV of patients were combined to construct a new parameter, that is A-PSAD = (age × total PSA [TPSA])/PV]. The area under the receiver-operating characteristic curve(AUC) of A-PSAD (0.728) for PCa diagnosis was higher than the AUCs of TPSA (0.581), free prostate-specific antigen (0.514), (F/T)PSA (0.535) and PSAD (0.696), with significant differences. Age, history of diabetes, TPSA and PV are risk factors for PCa(PSA:4-20ng/mL); in addition, A-PSAD has a moderate diagnostic value for PCa and may become a new indicator for PCa screening.
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Antígeno Prostático Específico , Neoplasias da Próstata , Biópsia , Detecção Precoce de Câncer , Humanos , Masculino , Próstata/diagnóstico por imagem , Próstata/patologia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia , Curva ROCRESUMO
The oxygen evolution reaction is critical to the efficiency of many energy technologies that store renewable electricity in chemical form. However, the rational design of high-performance and stable catalysts to drive this reaction remains a formidable challenge. Here, a facile ink-assisted strategy to construct a series of stable and advanced composite electrocatalysts with single Fe sites for permitting seriously improved performance characteristics is reported. As revealed by a suit of characterization techniques and theoretical methods, the improved electrocatalytic performance and stability can be attributed to the unique coordination states of Fe in the form of distorted FeO4 C and the interfacial effect in the composite system that optimize and stabilize single Fe sites in changing to better configurations for intermediates adsorption. The findings provide a novel strategy to in-depth understanding of practical guidelines for the electrocatalyst design for energy conversion devices.
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BACKGROUND ZW10 binding factor (ZWINT) has been reported to be upregulated in various human cancers and predict worse survival. However, the expression profile, clinical significance, and biological role of ZWINT remains unclear in breast cancer. MATERIAL AND METHODS In this study, we investigated messenger RNA (mRNA) and protein expression levels of ZWINT in breast cancer tissues, and the prognostic value of ZWINT protein expression was validated in a cohort of breast cancer patients using immunohistochemistry analysis. Then, different bioinformatic analyses were combined to explore the potential cancer-related hallmark underlying ZWINT in breast cancer, and a series of experiments in vitro were performed to reveal the oncogenic role of ZWINT in breast cancer. RESULTS Significant upregulation of ZWINT was observed in breast cancer tissues compared to normal and para-tumor tissues and upregulation of ZWINT predicts poor prognosis in breast cancer patients. Additionally, ZWINT could promote breast cancer proliferation via cell cycle regulation, especially by influencing the expression of some critical cell cycle regulators involved in G1 phase and G1/S transition. Finally, miR-204 was identified as a tumor suppressor microRNA which directly targets a specific site in 3'-UTR of ZWINT. CONCLUSIONS Overall, our results indicated that miR-204/ZWINT/cell cycle process might play an important role in breast cancer progression.
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Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Regiões 3' não Traduzidas , Ciclo Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Humanos , Imuno-Histoquímica , MicroRNAs , Proteínas Nucleares , Prognóstico , Análise de Sobrevida , Regulação para CimaRESUMO
The cell division cycle associated 5(CDCA5) was reported to be associated with progression of several human cancers, however, its clinical significance and biological role still remain unknown in gastric cancer(GC). By analyzing The Cancer Genome Atlas(TCGA), we found CDCA5 was significantly upregulated in GC tissues compared to adjacent normal tissues. Tissue microarray(TMA) indicated upregulation of CDCA5 was significantly correlated with more advanced clinicopathological features, and acts as an independent risk factor for worse overall survival(OS) in GC patients. Moreover, silence of CDCA5 suppresses proliferation of GC cells by inducing G1-phase arrest via downregulating Cyclin E1(CCNE1). Our results demonstrate upregulation of CDCA5 promotes GC malignant progression, which may offer a potential prognostic and therapeutic strategy.
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Proteínas Adaptadoras de Transdução de Sinal/genética , Adenocarcinoma/genética , Proteínas de Ciclo Celular/genética , Ciclina E/genética , Regulação Neoplásica da Expressão Gênica , Proteínas Oncogênicas/genética , Neoplasias Gástricas/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adenocarcinoma/diagnóstico , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Idoso , Animais , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Ciclina E/metabolismo , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Perfilação da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Transplante de Neoplasias , Proteínas Oncogênicas/metabolismo , Prognóstico , Transdução de Sinais , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Análise de Sobrevida , Análise Serial de TecidosRESUMO
In this paper, we discuss the emission of visible light by a monolithically integrated silicon gate-controlled diode with the p-n junction reverse-biased. Since the MOS-like diode utilizes the field effect to modulate the optical output, the modulation speed will benefit from this mechanism. Hence, a silicon gate-controlled diode structure for optical modulation analyzed its modulation principle, its dynamic characteristics are presented, and the bandwidth of the device is considered to approach GHz in theory due to the field-induced emission mechanism. The prototype MOS-like diode opens up the design of multiterminal silicon light emitting devices (LEDs), where gate electrodes with more than one gate contact overlap several junctions with different junction intersection geometries. The device appears as a good candidate for optical modulation within silicon technology.
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AbstractThe continuous emergence of highly immune-evasive SARS-CoV-2 variants has challenged vaccine efficacy. A vaccine that can provide broad protection is desirable. We evaluated the immunogenicity of a series of monovalent and bivalent adenovirus-vectored vaccines containing the spikes of Wildtype (WT), Beta, Delta, Omicron subvariants BA.1, BA.2, BA.2.12.1, BA.2.13, BA.3, BA.5, BQ.1.1, and XBB. Vaccination in mice using monovalent vaccines elicited the highest neutralizing titers against each self-matched strain, but against other variants were reduced 2- to 73-fold. A bivalent vaccine consisting of WT and BA.5 broadened the neutralizing breadth against pre-Omicron and Omicron subvariants except XBB. Among bivalent vaccines based on the strains before the emergence of XBB, a bivalent vaccine consisting of BA.2 and BA.5 elicited the most potent neutralizing antibodies against Omicron subvariants, including XBB. In mice primed with injected WT vaccine, intranasal booster with a bivalent vaccine containing XBB and BA.5 could elicit broad serum and respiratory mucosal neutralizing antibodies against all late Omicron subvariants, including XBB. In mice that had been sequentially vaccinated with WT and BA.5, intranasal booster with a monovalent XBB vaccine elicited greater serum and mucosal XBB neutralizing antibodies than bivalent vaccines containing XBB. Both monovalent and bivalent XBB vaccines induced neutralizing antibodies against EG.5. Unlike the antibody response, which is highly variant-specific, mice receiving either monovalent or bivalent vaccines elicited comparable T-cell responses against all variants. Furthermore, intranasal but not intramuscular booster-induced antigen-specific lung resident T cells. This study provides insights into the design of the COVID-19 vaccine and vaccination strategies.
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Introduction: Infection with SARS-CoV-2 begins in the upper respiratory tract and can trigger the production of mucosal spike-specific secretory IgA (sIgA), which provides protection against reinfection. It has been recognized that individuals with high level of nasal spike-specific IgA have a lower risk of reinfection. However, mucosal spike-specific sIgA wanes over time, and different individuals may have various level of spike-specific sIgA and descending kinetics, leading to individual differences in susceptibility to reinfection. A method for detecting spike-specific sIgA in the nasal passage would be valuable for predicting the risk of reinfection so that people at risk can have better preparedness. Methods: In this study, we describe the development of a colloidal gold-based immunochromatographic (ICT) strip for detecting SARS-CoV-2 Omicron spike-specific sIgA in nasal mucosal lining fluids (NMLFs). Results: The ICT strip was designed to detect 0.125 µg or more spike-specific sIgA in 80 µL of NMLFs collected using a nasal swab. Purified nasal sIgA samples from individuals who recently recovered from an Omicron BA.5 infection were used to demonstrate that this ICT strip can specifically detect spike-specific sIgA. The signal levels positively correlated with neutralizing activities against XBB. Subsequent analysis revealed that people with low or undetectable levels of spike-specific sIgA in the nasal passage were more susceptible to SARS-CoV-2 reinfection. Conclusions: This nasal spike-specific sIgA ICT strip provides a non-invasive, rapid, and convenient method to assess the risk of reinfection for achieving precision preparedness.
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The upper respiratory tract is the initial site of SARS-CoV-2 infection. Nasal spike-specific secretory immunoglobulin A (sIgA) correlates with protection against Omicron breakthrough infection. We report that intranasal vaccination using human adenovirus serotype 5 (Ad5) vectored Omicron spike in people who previously vaccinated with ancestral vaccine could induce robust neutralizing sIgA in the nasal passage. Nasal sIgA was predominantly present in dimeric and multimeric forms and accounted for nearly 40% of total proteins in nasal mucosal lining fluids (NMLFs). A low-level IgG could also be detected in NMLFs but not IgM, IgD, and IgE. After a complete nasal wash, sIgA in the nasal passage could be replenished rapidly within a few hours. A comparison of purified paired serum IgA, serum IgG, and nasal sIgA from the same individuals showed that sIgA was up to 3-logs more potent than serum antibodies in binding to spikes and in neutralizing Omicron subvariants. Serum IgG and IgA failed to neutralize XBB and BA.2.86, while nasal sIgA retained potent neutralization against these newly emerged variants. Further analysis showed that sIgA was more effective than IgG or IgA in blocking spike-mediated cell-to-cell transmission and protecting hACE2 mice from XBB challenge. Using a sIgA monoclonal antibody as a reference, we estimated that the total nasal sIgA contains about 2.6-3.9% spike-specific sIgA in NMLFs collected approximately one month after intranasal vaccination. Our study provided insights for developing intranasal vaccines that can induce sIgA to build an effective and mutation-resistant first-line immune barrier against constantly emerging variants.
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Administração Intranasal , Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Humanos , SARS-CoV-2/imunologia , SARS-CoV-2/genética , COVID-19/prevenção & controle , COVID-19/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Animais , Camundongos , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/genética , Vacinas contra COVID-19/administração & dosagem , Imunoglobulina A/imunologia , Imunoglobulina A/sangue , Imunoglobulina A/genética , Mucosa Nasal/imunologia , Mucosa Nasal/virologia , Feminino , Vetores Genéticos/imunologia , Vetores Genéticos/genética , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/imunologia , Imunoglobulina A Secretora/imunologia , Adenoviridae/genética , Adenoviridae/imunologia , Imunoglobulina G/imunologia , Imunoglobulina G/sangue , MasculinoRESUMO
Background: The long-term survival and perioperative outcomes of robotic-assisted lobectomy (RAL) and video-assisted lobectomy (VAL) in resectable non-small-cell lung cancer (NSCLC) were found to be comparable in retrospective studies, but they have not been investigated in a randomized trial setting. We conducted the RVlob trial to investigate if RAL was non-inferior to VAL in patients with resectable NSCLC. Methods: In this single-center, open-label, and parallel-arm randomized controlled trial conducted in Ruijin Hospital (Shanghai, China) between May 2017 and May 2020, we randomly assigned patients with resectable NSCLC in a 1:1 ratio to receive either RAL or VAL. One of the primary endpoints was 3-year overall survival. Secondary endpoints included 3-year disease-free survival. The Kaplan-Meier approach was used to calculate overall survival and disease-free survival at 3 years. This study was registered with ClinicalTrials.gov, NCT03134534. Findings: A total of 320 patients were randomized to receive RAL (n = 157) or VAL (n = 163). The baseline characteristics of patients were well balanced between the two groups. After a median follow-up of 58.0 months, the 3-year overall survival was 94.6% (95% confidence interval [CI], 91.0-98.3) in the RAL group and 91.5% (95% CI, 87.2-96.0) in the VAL group (hazard ratio [HR] for death, 0.65; 95% CI, 0.33-1.28; P = 0.21); noninferiority of RAL was confirmed according to the predefined margin of -5% (absolute difference, 2.96%; a one-sided 90% CI, -1.39% to ∞; P = 0.0029 for noninferiority). The 3-year disease-free survival was 88.7% (95% CI, 83.6-94.1) in the RAL group and 85.4% (95% CI, 80.0-91.2) in the VAL group (HR for disease recurrence or death, 0.87; 95% CI, 0.50-1.52; P = 0.62). Interpretation: This study is the first randomized trial to show that RAL resulted in non-inferior overall survival compared with VAL in patients with resectable NSCLC. Based on our results, RAL is an equally oncologically effective treatment and can be considered as an alternative to VAL for resectable NSCLC. Funding: National Natural Science Foundation of China (82072557), National Key Research and Development Program of China (2021YFC2500900), Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant (20172005, the 2nd round of disbursement), program of Shanghai Academic Research Leader from Science and Technology Commission of Shanghai Municipality (20XD1402300), Novel Interdisciplinary Research Project from Shanghai Municipal Health Commission (2022JC023), and Interdisciplinary Program of Shanghai Jiao Tong University (YG2023ZD04).
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To improve the accuracy of bearing fault diagnosis in a multisensor monitoring environment, it is necessary to obtain more accurate and effective fault classification features for bearings. Accordingly, a bearing fault classification feature extraction method based on multisensor fusion technology and an enhanced binary one-dimensional ternary pattern (EB-1D-TP) algorithm were proposed in this study. First, an optimal equalization weighting algorithm was established to realize high-precision fusion of bearing signals by introducing an optimal equalization factor and determining the theoretical optimal equalization factor value. Second, an enhanced binary encoding method similar to balanced ternary encoding was developed, which increases the difference between the different fault features of the bearing. Finally, the new sequence obtained after encoding was used as the input to a support vector machine to classify and diagnose the faults of the rolling bearing. The experimental results show that the algorithm can significantly improve the accuracy and speed of rolling-bearing fault classification. Combining fusion-encoding features with other intelligent classification methods, the classification results were improved.
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In order to realize the application of the nasal spray vaccination in the prevention and protection of respiratory infectious diseases, a nasal spray vaccination device is designed in this paper. The device uses a Laval nozzle structure to generate a high-speed airflow that impinges on the vaccine reagent and forms nebulized particles. Through optimizing of the Laval nozzle structure and testing experiments on spray particle size, spray velocity, spray angle and spray rate, a set of parameters which is applicable to actual nasal spray vaccination is obtained. The experimental results show that when the air source pressure is 2 bar, the spray angle is about 15°, the diameter of the spray particles Dv50 is about 17 µm, the volume fraction of particles with diameter smaller than 10um is about 24%, the spray rate is close to 300 µl/s. The vaccine activity tests demonstrate that under these conditions, not only the biological activity of vaccines is guaranteed, but also the delivery efficiency is well assured.
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Pulmão , Sprays Nasais , Aerossóis , Tamanho da Partícula , VacinaçãoRESUMO
In the past few decades, feedforward neural networks have gained much attraction in their hardware implementations. However, when we realize a neural network in analog circuits, the circuit-based model is sensitive to hardware nonidealities. The nonidealities, such as random offset voltage drifts and thermal noise, may lead to variation in hidden neurons and further affect neural behaviors. This paper considers that time-varying noise exists at the input of hidden neurons, with zero-mean Gaussian distribution. First, we derive lower and upper bounds on the mean square error loss to estimate the inherent noise tolerance of a noise-free trained feedforward network. Then, the lower bound is extended for any non-Gaussian noise cases based on the Gaussian mixture model concept. The upper bound is generalized for any non-zero-mean noise case. As the noise could degrade the neural performance, a new network architecture is designed to suppress the noise effect. This noise-resilient design does not require any training process. We also discuss its limitation and give a closed-form expression to describe the noise tolerance when the limitation is exceeded.
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Redes Neurais de Computação , Neurônios , Neurônios/fisiologia , Ruído , Distribuição NormalRESUMO
Acoustic resolution photoacoustic microscopy (AR-PAM) is a promising medical imaging modality that can be employed for deep bio-tissue imaging. However, its relatively low imaging resolution has greatly hindered its wide applications. Previous model-based or learning-based PAM enhancement algorithms either require design of complex handcrafted prior to achieve good performance or lack the interpretability and flexibility that can adapt to different degradation models. However, the degradation model of AR-PAM imaging is subject to both imaging depth and center frequency of ultrasound transducer, which varies in different imaging conditions and cannot be handled by a single neural network model. To address this limitation, an algorithm integrating both learning-based and model-based method is proposed here so that a single framework can deal with various distortion functions adaptively. The vasculature image statistics is implicitly learned by a deep convolutional neural network, which served as plug and play (PnP) prior. The trained network can be directly plugged into the model-based optimization framework for iterative AR-PAM image enhancement, which fitted for different degradation mechanisms. Based on physical model, the point spread function (PSF) kernels for various AR-PAM imaging situations are derived and used for the enhancement of simulation and in vivo AR-PAM images, which collectively proved the effectiveness of proposed method. Quantitatively, the PSNR and SSIM values have all achieve best performance with the proposed algorithm in all three simulation scenarios; The SNR and CNR values have also significantly raised from 6.34 and 5.79 to 35.37 and 29.66 respectively in an in vivo testing result with the proposed algorithm.
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BACKGROUND: Robot-assisted lobectomy (RAL) is increasingly used as an alternative to video-assisted lobectomy (VAL) for resectable non-small cell lung cancer (NSCLC). However, there is little evidence of any difference in postoperative health-related quality of life (HRQoL) between these two approaches. RESEARCH QUESTION: Is RAL superior to VAL in improving quality of life in patients with resectable NSCLC? STUDY DESIGN AND METHODS: We performed a single-center, open-label randomized clinical trial from May 2017 to May 2020 with 320 enrolled patients undergoing RAL or VAL for resectable NSCLC (RVlob trial; NCT03134534). Postoperative pain was evaluated by visual analog score or numeric rating score on postoperative day 1 and at weeks 4, 24, and 48. The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30), EORTC Quality of Life Questionnaire in Lung Cancer (QLQ-LC13), and the European Quality of Life 5 Dimensions (EQ-5D) questionnaire were also administered at weeks 4, 24, and 48 after surgery. RESULTS: One hundred and fifty-seven patients underwent RAL and 163 underwent VAL. The mean pain score of patients after RAL was significantly lower at week 4 (2.097 ± 0.111 vs 2.431 ± 0.108; P = .032). QLQ-C30 and QLQ-LC13 summary scores (P > .05) were similar for both RAL and VAL during the first 48 weeks of follow-up. HRQoL scores assessed with the EQ-5D questionnaire were also comparable between the two groups (P > .05) during the whole study period. INTERPRETATION: Both RAL and VAL showed satisfactory and comparable HRQoL and postoperative pain up to 48 weeks after surgery, despite some minor statistical differences at week 4. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03134534; URL: www. CLINICALTRIALS: gov.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Procedimentos Cirúrgicos Robóticos , Humanos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/tratamento farmacológico , Qualidade de Vida , Dor Pós-Operatória/epidemiologiaRESUMO
ABSTRACTProlonged infection and possible evolution of SARS-CoV-2 in patients living with uncontrolled HIV-1 infection highlight the importance of an effective vaccination regimen, yet the immunogenicity of COVID-19 vaccines and predictive immune biomarkers have not been well investigated. Herein, we report that the magnitude and persistence of antibody and cell-mediated immunity (CMI) elicited by an Ad5-vectored COVID-19 vaccine are impaired in SIV-infected macaques with high viral loads (> 105 genome copies per ml plasma, SIVhi) but not in macaques with low viral loads (< 105, SIVlow). After a second vaccination, the immune responses are robustly enhanced in all uninfected and SIVlow macaques. These responses also show a moderate increase in 70% SIVhi macaques but decline sharply soon after. Further analysis reveals that decreased antibody and CMI responses are associated with reduced circulating follicular helper T cell (TFH) counts and aberrant CD4/CD8 ratios, respectively, indicating that dysregulation of CD4+ T cells by SIV infection impairs the COVID-19 vaccine-induced immunity. Ad5-vectored COVID-19 vaccine shows no impact on SIV loads or SIV-specific CMI responses. Our study underscores the necessity of frequent booster vaccinations in HIV-infected patients and provides indicative biomarkers for predicting vaccination effectiveness in these patients.