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Purpose: To use hepatic uptake index (HUI) of liver lobes on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) to discriminate between patients with hepatitis B-related cirrhosis in compensated and decompensated statuses. Methods: Forty-four consecutive patients with hepatitis B-related cirrhosis who underwent Gd-EOB-DTPA-enhanced MRI were divided into compensated and decompensated statuses based on clinical evaluation. Volume and signal intensity of individual lobes were retrospectively measured to calculate HUI of the right liver lobe (RHUI), medial (MHUI) and lateral (LHUI) left liver lobes, and caudate lobe (CHUI). Spearman's rank correlation analyses were performed to evaluate relationships of lobe-based HUI with Child-Pugh and model for end-stage liver disease (MELD) scoring system scores in compensated and decompensated statuses. The Mann-Whitney U-test was used to compare the lobe-based HUI between compensated and decompensated statuses. The performance of lobe-based HUI in distinguishing cirrhosis was evaluated using receiver operating characteristic (ROC) analysis, and the area under the ROC curve (AUC) was calculated as a measure of accuracy. Delong's method was used for statistical analysis to elucidate which HUI is optimal. Results: Compensated and decompensated liver cirrhosis were confirmed in 25 (56.82%) and 19 (43.18%) patients, respectively. According to Spearman's rank correlation analysis, RHUI, MHUI, LHUI, and CHUI were all significantly associated with Child-Pugh and MELD scores (all P values <0.05). Receiver operating characteristic analysis demonstrated that among all lobe-based HUI parameters, RHUI could best perform the previous discrimination with a cut-off of 485.73 and obtain an AUC of 0.867. The AUC of RHUI improved and was significantly different from that of MHUI, LHUI, and CHUI (P = 0.03, P = 0.007, and P < 0.001, respectively, Delong's test). Conclusions: The RHUI could help quantitatively discriminate hepatitis B-related cirrhosis between compensated and decompensated statuses.
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Meios de Contraste , Gadolínio DTPA , Cirrose Hepática , Fígado , Imageamento por Ressonância Magnética , Humanos , Gadolínio DTPA/farmacocinética , Gadolínio DTPA/administração & dosagem , Cirrose Hepática/diagnóstico por imagem , Feminino , Masculino , Meios de Contraste/farmacocinética , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Fígado/diagnóstico por imagem , Adulto , Curva ROC , Idoso , Índice de Gravidade de Doença , Hepatite B/complicações , Hepatite B/diagnóstico por imagemRESUMO
An autoencoder for video anomaly detection task is a type of algorithm with the primary purpose of learning an "informative" representation of the normal data that can be used for identifying the abnormal data by learning to reconstruct a set of input observations. Based on the encoding-decoding structure, we explore a novel dual ForkNet architecture that can dissociate and process the spatio-temporal representation. It is well-known in the information theory community that most autoencoders coding processes are inevitably accompanied by a certain loss of information. In this dual ForkNet, we focus on mitigating the information loss problem and propose a novel architectural recalibration approach, which we term the "Informetrics Recalibration" (IR). It can adaptively recalibrate latent feature representation by explicitly modeling the similarity between the corresponding feature maps of encoder and decoder, and retain more useful semantic information to generate greater differentiation between normal and abnormal events. Additionally, because the structure of the autoencoder itself determines the difficulty to obtain deep semantic information, we introduce a Secondary Encoder (SE) in each ForkNet, so as to recalibrate target features responses of latent feature representation. Our model is easy to be trained and robust to be applied, because it basically consists of some ResNet blocks without using complicated modules. Extensive experiments on the five publicly available benchmarks show that our model outperforms the existing state-of-the-art architectures, demonstrating our framework's effectiveness.
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Accurate segmentation of retinal vessels is of great significance for computer-aided diagnosis and treatment of many diseases. Due to the limited number of retinal vessel samples and the scarcity of labeled samples, and since grey theory excels in handling problems of "few data, poor information", this paper proposes a novel grey relational-based method for retinal vessel segmentation. Firstly, a noise-adaptive discrimination filtering algorithm based on grey relational analysis (NADF-GRA) is designed to enhance the image. Secondly, a threshold segmentation model based on grey relational analysis (TS-GRA) is designed to segment the enhanced vessel image. Finally, a post-processing stage involving hole filling and removal of isolated pixels is applied to obtain the final segmentation output. The performance of the proposed method is evaluated using multiple different measurement metrics on publicly available digital retinal DRIVE, STARE and HRF datasets. Experimental analysis showed that the average accuracy and specificity on the DRIVE dataset were 96.03% and 98.51%. The mean accuracy and specificity on the STARE dataset were 95.46% and 97.85%. Precision, F1-score, and Jaccard index on the HRF dataset all demonstrated high-performance levels. The method proposed in this paper is superior to the current mainstream methods.
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Algoritmos , Processamento de Imagem Assistida por Computador , Vasos Retinianos , Vasos Retinianos/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador/métodosRESUMO
Oomycete secretes a range of RxLR effectors into host cells to manipulate plant immunity by targeting proteins from several organelles. In this study, we report that chloroplast protein StFC-II is hijacked by a pathogen effector to enhance susceptibility. Phytophthora infestans RxLR effector Pi22922 is activated during the early stages of P. infestans colonization. Stable overexpression of Pi22922 in plants suppresses flg22-triggered reactive oxygen species (ROS) burst and enhances leaf colonization by P. infestans. A potato ferrochelatase 2 (FC-II, a nuclear-encoded chloroplast-targeted protein), a key enzyme for heme biosynthesis in chloroplast, was identified as a target of Pi22922 in the cytoplasm. The pathogenicity of Pi22922 in plants is partially dependent on FC-II. Overexpression of StFC-II decreases resistance of potato and Nicotiana benthamiana against P. infestans, and silencing of NbFC-II in N. benthamiana reduces P. infestans colonization. Overexpression of StFC-II increases heme content and reduces chlorophyll content and photosynthetic efficiency in potato leaves. Moreover, ROS accumulation both in chloroplast and cytoplasm is attenuated and defense-related genes are down-regulated in StFC-II overexpression transgenic potato and N. benthamiana leaves. Pi22922 inhibits E3 ubiquitin ligase StCHIP-mediated StFC-II degradation in the cytoplasm and promotes its accumulation in chloroplasts. In summary, this study characterizes a new mechanism that an oomycete RxLR effector suppresses host defenses by promoting StFC-II accumulation in chloroplasts, thereby compromising the host immunity and promoting susceptibility.
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Introduction: Testicular cancer (TC) is the most frequent cancer among men aged 14-44 years. The risk of erectile dysfunction (ED) in TC patients varied within a wide range across different studies. This study aims to estimate the risk of ED in TC patients by conducting a meta-analysis of case-control studies. Material and methods: Relevant studies were searched using PubMed, EMBASE, Scopus, and the Cochrane Library up to June 2019. Case-control studies that reported the incidence of ED in TC patients were included. Results: A total of 8 studies involving 2060 TC patients and 2651 healthy men were included. All the TC patients underwent unilateral orchiectomy; other treatment modalities were also conducted if necessary. ED occurred in 16.9% (348/2060) of TC patients and 9.4% (251/2651) of healthy men. Compared with healthy men, TC patients experienced a significantly increased risk of ED (OR = 2.39, 95% CI: 1.56-3.67). Substantial heterogeneity was observed. In addition, subgroup analysis revealed that the risk (OR = 3.76, 95% CI: 2.45-5.78) for ED in TC patients with follow-up < 5 years was significantly higher than that (OR = 1.61, 95% CI: 1.10-3.67) with follow-up ≥ 5 years. Heterogeneity was improved after subgroup analysis. Conclusions: TC patients experienced an increased risk for ED compared with healthy men. The long-term risk for ED in TC patients was lower than the short-term risk.
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Excessive alcohol consumption is considered to be a major risk factor of alcohol-induced osteonecrosis of the femoral head (AONFH). The gut microbiota (GM) has been reported to aid in the regulation of human physiology and its composition can be altered by alcohol consumption. The aim of the present study was to improve the understanding of the GM and its metabolites in patients with AONFH. Metabolomic sequencing and 16S rDNA analysis of fecal samples were performed using liquid chromatography-mass spectrometry to characterize the GM of patients with AONFH and healthy normal controls (NCs). Metagenomic sequencing of fecal samples was performed to identify whether GM changes on the species level were associated with the expression of gut bacteria genes or their associated functions in patients with AONFH. The abundance of 58 genera was found to differ between the NC group and the AONFH group. Specifically, Klebsiella, Holdemanella, Citrobacter and Lentilactobacillus were significantly more abundant in the AONFH group compared with those in the NC group. Metagenomic sequencing demonstrated that the majority of the bacterial species that exhibited significantly different abundance in patients with AONFH belonged to the genus Pseudomonas. Fecal metabolomic analysis demonstrated that several metabolites were present at significantly different concentrations in the AONFH group compared with those in the NC group. These metabolites were products of vitamin B6 metabolism, retinol metabolism, pentose and glucuronate interconversions and glycerophospholipid metabolism. In addition, these changes in metabolite levels were observed to be associated with the altered abundance of specific bacterial species, such as Basidiobolus, Mortierella, Phanerochaete and Ceratobasidium. According to the results of the present study, a comprehensive landscape of the GM and metabolites in patients with AONFH was revealed, suggesting the existence of interplay between the gut microbiome and metabolome in AONFH pathogenesis.
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Previous studies have demonstrated that Staphylococcus cohnii WX_M8 and S. saprophyticus MY_A10 significantly enhanced the flavor of Chinese bacon in a mixed fermentation. However, due to the complexity of the processing, the contribution of the bacteria is deceptive when investigating only the phenotypic changes at the time of fermentation. In order to clarify the metabolic mechanisms of mixed fermentation, a technological characterization, whole genome and comparative genomics analysis, and metabolites were approached in this study. Results showed that differences in tolerance characteristics existed between WX_M8 and MY_A10. And the genomes of both the two strains consisted of one chromosome and four circular plasmids. Their genome sizes were 2.74 Mp and 2.62 Mp, the GC contents were 32.45% and 33.18%, and the predicted coding genes (CDS) were 2564 and 2541, respectively. Based on the annotation of gene functions and assessment of metabolic pathways in the KEGG database, WX_M8 and MY_A10 strains were found to harbor complete protein degradation and amino acid metabolic pathways, pyruvate and butanol metabolic pathways, and isoleucine metabolic pathways, and their diverse enzyme-encoding genes superimposed the metabolic functions, whereas the alcohol dehydrogenase genes, adh and frmA, achieved complementary functions in the production of esters. Comparative genomics analysis revealed a diversity of encoding genes of aminotransferases and a greater metabolism for sulfur-containing amino acids, aromatic amino acids, and branched-chain amino acids in the mixed fermentation of strains WX_M8 and MY_A10. Metabolites analysis showed that MY_A10 focused on the production of soluble peptides and free amino acids (FAAs), while WX_M8 focused on volatile organic compounds (VOCs), resulting in a significant enhancement of the flavor of Chinese bacon when the two were mixed fermented. This result may provide direction for strains WX_M8 and MY_A10 to be used as starter cultures and targeted to regulate flavor.
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Fermentação , Genoma Bacteriano , Genômica , Staphylococcus , Staphylococcus/genética , Staphylococcus/metabolismo , Microbiologia de Alimentos , Staphylococcus saprophyticus/genética , Staphylococcus saprophyticus/metabolismo , Redes e Vias Metabólicas/genética , Produtos da Carne/microbiologiaRESUMO
BACKGROUND: Spermatogenesis is a highly regulated and complex process in which DNA methylation plays a crucial role. This study aimed to explore the differential methylation profiles in sperm DNA between patients with asthenospermia (AS) and healthy controls (HCs), those with oligoasthenospermia (OAS) and HCs, and patients with AS and those with OAS. RESULTS: Semen samples and clinical data were collected from five patients with AS, five patients with OAS, and six age-matched HCs. Reduced representation bisulfite sequencing (RRBS) was performed to identify differentially methylated regions (DMRs) in sperm cells among the different types of patients and HCs. A total of 6520, 28,019, and 16,432 DMRs were detected between AS and HC, OAS and HC, and AS and OAS groups, respectively. These DMRs were predominantly located within gene bodies and mapped to 2868, 9296, and 9090 genes in the respective groups. Of note, 12, 9, and 8 DMRs in each group were closely associated with spermatogenesis and male infertility. Furthermore, BDNF, SMARCB1, PIK3CA, and DDX27; RBMX and SPATA17; ASZ1, CDH1, and CHDH were identified as strong differentially methylated candidate genes in each group, respectively. Meanwhile, the GO analysis of DMR-associated genes in the AS vs. HC groups revealed that protein binding, cytoplasm, and transcription (DNA-templated) were the most enriched terms in the biological process (BP), cellular component (CC), and molecular function (MF), respectively. Likewise, in both the OAS vs. HC and AS vs. OAS groups, GO analysis revealed protein binding, nucleus, and transcription (DNA-templated) as the most enriched terms in BP, CC, and MF, respectively. Finally, the KEGG analysis of DMR-annotated genes and these genes at promoters suggested that metabolic pathways were the most significantly associated across all three groups. CONCLUSIONS: The current study results revealed distinctive sperm DNA methylation patterns in the AS vs. HC and OAS vs. HC groups, particularly between patients with AS and those with OAS. The identification of key genes associated with spermatogenesis and male infertility in addition to the differentially enriched metabolic pathways may contribute to uncovering the potential pathogenesis in different types of abnormal sperm parameters.
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Astenozoospermia , Metilação de DNA , Oligospermia , Humanos , Masculino , Astenozoospermia/genética , Adulto , Oligospermia/genética , Espermatozoides/metabolismo , Espermatogênese/genética , Estudos de Casos e Controles , Epigênese GenéticaRESUMO
The efficacy of adoptive T cell therapy (ACT) for the treatment of solid tumors remains challenging. In addition to the poor infiltration of effector T (Teff) cells limited by the physical barrier surrounding the solid tumor, another major obstacle is the extensive infiltration of regulatory T (Treg) cells, a major immunosuppressive immune cell subset, in the tumor microenvironment. Here, this work develops a grooved microneedle patch for augmenting ACT, aiming to simultaneously overcome physical and immunosuppressive barriers. The microneedles are engineered through an ice-templated method to generate the grooved structure for sufficient T-cell loading. In addition, with the surface modification of chemokine CCL22, the MNs could not only directly deliver tumor-specific T cells into solid tumors through physical penetration, but also specifically divert Treg cells from the tumor microenvironment to the surface of the microneedles via a cytokine concentration gradient, leading to an increase in the ratio of Teff cells/Treg cells in a mouse melanoma model. Consequently, this local delivery strategy of both T cell receptor T cells and chimeric antigen receptor T cells via the CCL22-modified grooved microneedles as a local niche could significantly enhance the antitumor efficacy and reduce the on-target off-tumor toxicity of ACT.
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Imunoterapia Adotiva , Agulhas , Linfócitos T Reguladores , Animais , Linfócitos T Reguladores/imunologia , Camundongos , Imunoterapia Adotiva/métodos , Microambiente Tumoral , Linhagem Celular Tumoral , Quimiocina CCL22/metabolismo , Humanos , Camundongos Endogâmicos C57BL , Neoplasias/terapia , Neoplasias/imunologiaRESUMO
Thermo-responsive smart materials have aroused extensive interest due to the particular significance of temperature sensing. Although various photoluminescent materials are explored in thermal detection, it is not applicable enough in X-ray radiation environment where the accuracy and reliability will be influenced. Here, a strategy is proposed by introducing the concept of radio-luminescent functional building units (RBUs) to construct thermo-responsive lanthanide metal-organic frameworks (Ln-MOFs) scintillators for self-calibrating thermometry. The rational designs of RBUs (including organic ligand and Tb3+/Eu3+) with appropriate energy levels lead to high-performance radio-luminescence. Ln-MOFs scintillators exhibit perfect linear response to X-ray, presenting low dose rate detection limit (min ≈156.1 nGyairs-1). Self-calibrating detection based on ratiometric XEL intensities is achieved with good absolute and relative sensitivities of 6.74 and 8.1%K-1, respectively. High relative light yield (max ≈39000 photons MeV-1), imaging spatial resolution (max ≈18 lp mm-1), irradiation stability (intensity ≈100% at 368 K in total dose up to 215 Gyair), and giant color transformation visualization benefit the applications, especially the in situ thermo-responsive X-ray imaging. Such strategy provides a promising way to develop the novel smart photonic materials with excellent scintillator performances.
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Dual humanoid robot collaborative control systems possess better flexibility and adaptability in complex environments due to their similar structures to humans. This paper adopts a distributed model predictive controller based on the leader-follower approach to address the collaborative transportation control issue of dual humanoid robots. In the dual-robot collaborative control system, network latency issues may arise due to unstable network conditions, affecting the consistency of dual-robot collaboration. To solve this issue, a communication protocol was constructed through socket communication for dual-robot collaborative consistency, thereby resolving the problem of consistency in dual humanoid robot collaboration. Additionally, due to the complex structure of humanoid robots, there are deficiencies in position tracking accuracy during movement. To address the poor accuracy in position tracking, this paper proposes a distributed model predictive control that considers historical cumulative error, thus enhancing the position tracking accuracy of dual-robot collaborative control.
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Background: The prevalence of diabetes has risen fast with a considerable weighted prevalence of undiagnosed diabetes or uncontrolled diabetes. Then it becomes more necessary to timely screen out and monitor high-risk populations who are likely to be ignored during the COVID-19 pandemic. To classify and find the common risks of undiagnosed diabetes and uncontrolled diabetes, it's beneficial to put specific risk control measures into effect for comprehensive primary care. Especially, there is a need for accurate yet accessible prediction models. Objective: Based on a cross-sectional study and secondary analysis on the health examination held in Changchun City (2016), we aimed to evaluate the factors associated with hyperglycemia, analyze the management status of T2DM, and determine the best cutoff value of incidence of diabetes in the first-degree relatives to suggest the necessity of early diagnosis of diabetes after first screening. Results: A total of 5658 volunteers were analyzed. Prevalence of T2DM and impaired fasting glucose were 8.4% (n=477) and 11.5% (n=648), respectively. There were 925 participants (16.3%) with a family history of T2DM in their first-degree relatives. Multivariable analysis demonstrated that family history was associated with hyperglycemia. Among the 477 patients with T2DM, 40.9% had not been previously diagnosed. The predictive equation was calculated with the following logistic regression parameters with 0.71 (95% CI: 0.67-0.76) of the area under the ROC curve, 64.0% of sensitivity and 29% of specificity (P < 0.001): P = \frac{1}{1 + e^{-z}}, where z = -3.08 + [0.89 (Family history-group) + 0.69 (age-group)+ 0.25 (BMI-group)]. Positive family history was associated with the diagnosis of T2DM, but not glucose level in the diagnosed patients. The best cutoff value of incidence of diabetes in the first-degree relatives was 9.55% (P < 0.001). Conclusions: Family history of diabetes was independently associated with glucose dysfunction. Classification by the first-degree relatives with diabetes is prominent for targeting high-risk population. Meanwhile, positive family history of diabetes was associated with diabetes being diagnosed rather than the glycemic control in patients who had been diagnosed. It's necessary to emphasize the linkage between early diagnosis and positive family history for high proportions of undiagnosed T2DM.
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Diabetes Mellitus Tipo 2 , Humanos , Feminino , Masculino , China/epidemiologia , Pessoa de Meia-Idade , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/diagnóstico , Fatores de Risco , Adulto , Prevalência , COVID-19/epidemiologia , Glicemia/análise , Família , Idoso , Hiperglicemia/epidemiologia , IncidênciaRESUMO
BACKGROUND: Predicting early recurrence (ER) of hepatocellular carcinoma (HCC) accurately can guide treatment decisions and further enhance survival. Computed tomography (CT) imaging, analyzed by deep learning (DL) models combining domain knowledge, has been employed for the prediction. However, these DL models utilized late fusion, restricting the interaction between domain knowledge and images during feature extraction, thereby limiting the prediction performance and compromising decision-making interpretability. METHODS: We propose a novel Vision Transformer (ViT)-based DL network, referred to as Dual-Style ViT (DSViT), to augment the interaction between domain knowledge and images and the effective fusion among multi-phase CT images for improving both predictive performance and interpretability. We apply the DSViT to develop pre-/post-operative models for predicting ER. Within DSViT, to balance the utilization between domain knowledge and images within DSViT, we propose an adaptive self-attention mechanism. Moreover, we present an attention-guided supervised learning module for balancing the contributions of multi-phase CT images to prediction and a domain knowledge self-supervision module for enhancing the fusion between domain knowledge and images, thereby further improving predictive performance. Finally, we provide the interpretability of the DSViT decision-making. RESULTS: Experiments on our multi-phase data demonstrate that DSViTs surpass the existing models across multiple performance metrics and provide the decision-making interpretability. Additional validation on a publicly available dataset underscores the generalizability of DSViT. CONCLUSIONS: The proposed DSViT can significantly improve the performance and interpretability of ER prediction, thereby fortifying the trustworthiness of artificial intelligence tool for HCC ER prediction in clinical settings.
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Carcinoma Hepatocelular , Aprendizado Profundo , Neoplasias Hepáticas , Recidiva Local de Neoplasia , Tomografia Computadorizada por Raios X , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Recidiva Local de Neoplasia/diagnóstico por imagemRESUMO
Background: Despite the widespread adoption of combination antiretroviral therapy (cART) in managing HIV, the virus's impact on the brain structure of patients remains significant. This study aims to longitudinally explore the persistent effects of HIV on brain structure, focusing on changes in gray matter volume (GMV) and structural covariance network (SCN) among patients at the Asymptomatic Neurocognitive Impairment (ANI) stage. Methods: This research involved 45 HIV patients diagnosed with ANI and 45 demographically matched healthy controls (HCs). The participants were observed over a 1.5-year period. Differences in GMV between groups were analyzed using voxel-based morphometry (VBM), while the graph theory model facilitated the establishment of topological metrics for assessing network indices. These differences were evaluated using two-sample t-tests and paired-sample t-tests, applying the network-based statistics method. Additionally, the study examined correlations between GMV and cognitive performance, as well as clinical variables. Results: Compared with HCs, HIV patients demonstrated reduced GMV in the right middle temporal gyrus and left middle frontal gyrus (FWE, p < 0.05), along with decreased betweenness centrality (BC) in the left anterior cingulate and paracingulate cortex. Conversely, an increase in the clustering coefficient (Cp) was observed (FDR, p < 0.05). During the follow-up period, a decline in GMV in the right fusiform gyrus (FWE, p < 0.05) and a reduction in node efficiency (Ne) in the triangular part of the inferior frontal gyrus were noted compared with baseline measurements (FDR, p < 0.05). The SCN of HIV patients exhibited small-world properties across most sparsity levels (Sigma >1), and area under the curve (AUC) analysis revealed no significant statistical differences between groups. Conclusion: The findings suggest that despite the administration of combination antiretroviral therapy (cART), HIV continues to exert slow and sustained damage on brain structures. However, when compared to HCs, the small-world properties of the patients' SCNs did not significantly differ, and the clustering coefficient, indicative of the overall information-processing capacity of the brain network, was slightly elevated in HIV patients. This elevation may relate to compensatory effects of brain area functions, the impact of cART, functional reorganization, or inflammatory responses.
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BACKGROUND AND OBJECTIVE: Combinations of immune checkpoint inhibitors and nab-paclitaxel have achieved significant therapeutic effects in the treatment of advanced urothelial carcinoma. Our aim was to assess the efficacy and safety of tislelizumab combined with low-dose nab-paclitaxel in patients with muscle-invasive bladder cancer (MIBC). METHODS: TRUCE-01 was a single-arm phase 2 study that included 62 patients with T2-4a N0/X M0 MIBC tumors with predominant urothelial carcinoma histology. Eligible patients received three 21-d cycles of intravenous 200 mg tislelizumab on day 1 plus intravenous 200 mg nab-paclitaxel on day 2, followed by surgical assessment. The primary study endpoint was a clinical complete response (cCR). Treatment-related adverse event (TRAE) profiles were recorded according to Common Terminology Criteria for Adverse Events version 5.0. KEY FINDINGS AND LIMITATIONS: The safety analysis included all 62 patients and the efficacy analysis included 48 patients. The primary efficacy endpoint (cCR) was met by 25 patients (52%) patients. Among the 62 patients in the safety analysis, six (9.7%) had grade ≥3 TRAEs. CONCLUSIONS: Tislelizumab combined with low-dose nab-paclitaxel showed promising antitumor effectiveness and was generally well tolerated, which makes it an excellent preoperative therapy option for MIBC. PATIENT SUMMARY: We found that a combination of the drugs tislelizumab and low-dose nab-paclitaxel had satisfactory efficacy and safety for preoperative treatment of muscle-invasive bladder cancer.
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Carbon-fixing bacterial communities are essential drivers of carbon fixation in estuarine ecosystems that critically affect the global carbon cycle. This study compared the abundances of the Calvin cycle functional genes cbbL and cbbM and Reductive tricarboxylic acid cycle gene aclB, as well as compared carbon-fixing bacterial community features in the two estuaries, predicted potential ecological functions of carbon-fixation bacteria, and analyzed their symbiosis strategies in two estuaries having different geographical distributions. Gammaproteobacteria was the dominant carbon-fixing bacterial community in the two estuaries. However, a higher number of Alphaproteobacteria were noted in the Liaohe Estuary, and a higher number of Betaproteobacteria were found in the Yalujiang Estuary. The carbon-fixing functional gene levels exhibited the order of aclB > cbbL > cbbM, and significant effects of Cu, Pb, and petroleum were observed (p < 0.05). Nitrogen-associated nutrient levels are major environmental factors that affect carbon-fixing bacterial community distribution patterns. Spatial factors significantly affected cbbL carbon-fixing functional bacterial community structure more than environmental factors. With the increase in offshore distance, the microbial-led processes of methylotrophy and nitrogen fixation gradually weakened, but a gradual strengthening of methanotrophy and nitrification was observed. Symbiotic network analysis of the microorganisms mediating these ecological processes revealed that the carbon-fixing bacterial community in these two estuaries had a non-random symbiotic pattern, and microbial communities from the same module were strongly linked among the carbon, nitrogen, and sulfur cycle. These findings could advance the understanding of carbon fixation in estuarine ecosystems.
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Bactérias , Ciclo do Carbono , Estuários , Bactérias/genética , Bactérias/classificação , Carbono/metabolismo , Microbiota , Ecossistema , China , Fixação de NitrogênioRESUMO
Endosymbionts regulate the behavior of pest species, which could provide insights into their control. The citrus leafminer (Phyllocnistis citrella Stainton) is a widely distributed pest associated with diseases of citrus, especially of young trees. Here, we determined the endosymbiont composition of P. citrella in citrus orchards across China. The resulting dataset comprised average 50,430 high-quality reads for bacterial 16S rRNA V3-V4 regions of endosymbionts from 36 P. citrella larvae sampled from 12 citrus orchards across China. The sequencing depth and sampling size of this dataset were sufficient to reveal most of the endosymbionts of P. citrella. In total, 2,875 bacterial amplicon sequence variants were obtained; taxonomic analysis revealed a total of 372 bacterial genera, most of which were Proteobacteria phylum with Undibacterium being the most abundant genus. This dataset provides the first evidence of P. citrella endosymbionts that could support the development of pest management approaches in citrus orchards.
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Bactérias , Citrus , Mariposas , Simbiose , Animais , Bactérias/classificação , Bactérias/genética , China , Larva/microbiologia , Mariposas/microbiologia , RNA Ribossômico 16S/genéticaRESUMO
We conducted a phase I, randomized, double-blind, placebo-controlled trial including healthy adults in Sui County, Henan Province, China. Ninety-six adults were randomly assigned to one of three groups (high-dose, medium-dose, and low-dose) at a 3:1 ratio to receive one vaccine dose or placebo. Adverse events up to 28 days after each dose and serious adverse events up to 6 months after all doses were reported. Geometric mean titers and seroconversion rates were measured for anti-rotavirus neutralizing antibodies using microneutralization tests. The rates of total adverse events in the placebo group, low-dose group, medium-dose group, and high-dose group were 29.17 % (12.62 %-51.09 %), 12.50 % (2.66 %-32.36 %), 50.00 % (29.12 %-70.88 %), and 41.67 % (22.11 %-63.36 %), respectively, with no significant difference in the experimental groups compared with the placebo group. The results of the neutralizing antibody assay showed that in the adult group, the neutralizing antibody geometric mean titer at 28 days after full immunization in the low-dose group was 583.01 (95 % confidence interval [CI]: 447.12-760.20), that in the medium-dose group was 899.34 (95 % CI: 601.73-1344.14), and that in the high-dose group was 1055.24 (95 % CI: 876.28-1270.75). The GMT of serum-specific IgG at 28 days after full immunization in the low-dose group was 3444.26 (95 % CI: 2292.35-5175.02), that in the medium-dose group was 6888.55 (95 % CI: 4426.67-10719.6), and that in the high-dose group was 7511.99 (95 % CI: 3988.27-14149.0). The GMT of serum-specific IgA at 28 days after full immunization in the low-dose group was 2332.14 (95 % CI: 1538.82-3534.45), that in the medium-dose group was 4800.98 (95 % CI: 2986.64-7717.50), and that in the high-dose group was 3204.30 (95 % CI: 2175.66-4719.27). In terms of safety, adverse events were mainly Grades 1 and 2, indicating that the safety of the vaccine is within the acceptable range in the healthy adult population. Considering the GMT and positive transfer rate of neutralizing antibodies for the main immunogenicity endpoints in the experimental groups, it was initially observed that the high-dose group had higher levels of neutralizing antibodies than the medium- and low-dose groups in adults aged 18-49 years. This novel inactivated rotavirus vaccine was generally well-tolerated in adults, and the vaccine was immunogenic in adults (ClinicalTrials.gov number, NCT04626856).
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Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra Rotavirus , Vacinas de Produtos Inativados , Humanos , Adulto , Método Duplo-Cego , Masculino , Feminino , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/efeitos adversos , Vacinas contra Rotavirus/imunologia , Vacinas contra Rotavirus/administração & dosagem , Vacinas contra Rotavirus/efeitos adversos , China , Imunogenicidade da Vacina , Infecções por Rotavirus/prevenção & controle , Infecções por Rotavirus/imunologia , Rotavirus/imunologia , Voluntários Saudáveis , Testes de NeutralizaçãoRESUMO
This study delves into the potential connections between cardiac oxidative stress, inflammatory cytokine response, cardiac pump function, and prognosis in individuals following myocardial infarction. A total of 276 patients were categorized into two groups: the control group (n = 130) and the observation group (n = 146), based on the drug intervention strategies. The control group received standard drug treatment, while the observation group received early drug intervention targeting antioxidant and anti-inflammatory treatment in addition to standard treatment. Serum levels of inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-9 (IL-6), were assessed using enzyme-linked immuno sorbent assay (ELISA) kits. The Forkhead Box Protein A2 (FOX2) reagent was used to determine the overall oxidation level. Left Ventricular End-Diastolic Diameter (LVEDD), Left Ventricular Ejection Fraction (LVEF), and End-Systolic Diameter (ESD) were measured using Doppler ultrasound. The observation group exhibited significantly reduced serum levels of TNF-α, IL-1ß, and IL-6 compared to the control group (P < 0.05). Moreover, the observation group exerted lower total oxidation levels, OSI, EDD, and ESD compared to the control group (P < 0.05), while the LVEF and TAS levels in the observation group were higher than those in the control group (P < 0.05). Remarkably, the observation group experienced a significant reduction in the incidences of reinfarction, heart failure, arrhythmia, and abnormal valve function compared to the control group (P < 0.05). Decreased cardiac pump function and a more unfavorable prognosis were associated with elevated levels of cardiac oxidative stress and inflammatory factors (P < 0.05). Timely intervention with appropriate medications have a crucial effect in decreasing inflammatory marker levels, mitigating oxidative pressure, and enhancing cardiac pumping capacity and overall prognosis.
Assuntos
Citocinas , Infarto do Miocárdio , Humanos , Citocinas/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Volume Sistólico , Interleucina-6/metabolismo , Função Ventricular Esquerda , Infarto do Miocárdio/metabolismo , Prognóstico , Estresse OxidativoRESUMO
The aroma profiles in non-smoked bacon were investigated via GC-O-MS, GC × GC-TOFMS, and GC-IMS. GC-O-MS is advantageous for detecting aldehydes. GC × GC-TOFMS is more sensitive to hydrocarbons and alcohols, while GC-IMS detects a balanced range of categories. Only 9 of the 239 detected volatiles were identifiable by all three methods. Therefore, the combination of all three methods proved to be the most effective way to comprehensively analyze the aroma profiles of bacon. Recombination and omission tests were performed using aroma compounds with a flavor dilution (FD) factor greater than 27; five volatiles were identified as key aroma compounds in non-smoked bacon, including hexanal, (E,E)-2,4-decadienal, 1-octen-3-ol, dihydro-5-pentyl-2(3H)-furanone, and 3-methyl-butanoic acid. Among these, hexanal and 1-octen-3-ol exhibited relatively high FD factors and odor activity values (OAVs), so they were confirmed as the primary contributors. Meanwhile, seven volatiles contributed to the unique aroma of non-smoked bacon in different regions. The difference in the aroma of bacon in different regions is mainly due to the content of various volatiles rather than the type. A comprehensive analysis of the aroma in non-smoked bacon can reveal theoretical information for improving the process and quality control of the product.