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1.
Artigo em Inglês | MEDLINE | ID: mdl-38607711

RESUMO

3D dense captioning requires a model to translate its understanding of an input 3D scene into several captions associated with different object regions. Existing methods adopt a sophisticated "detect-then-describe" pipeline, which builds explicit relation modules upon a 3D detector with numerous hand-crafted components. While these methods have achieved initial success, the cascade pipeline tends to accumulate errors because of duplicated and inaccurate box estimations and messy 3D scenes. In this paper, we first propose Vote2Cap-DETR, a simple-yet-effective transformer framework that decouples the decoding process of caption generation and object localization through parallel decoding. Moreover, we argue that object localization and description generation require different levels of scene understanding, which could be challenging for a shared set of queries to capture. To this end, we propose an advanced version, Vote2Cap-DETR++, which decouples the queries into localization and caption queries to capture task-specific features. Additionally, we introduce the iterative spatial refinement strategy to vote queries for faster convergence and better localization performance. We also insert additional spatial information to the caption head for more accurate descriptions. Without bells and whistles, extensive experiments on two commonly used datasets, ScanRefer and Nr3D, demonstrate Vote2Cap-DETR and Vote2Cap-DETR++ surpass conventional "detect-then-describe" methods by a large margin. We have made the code available at https://github.com/ch3cook-fdu/Vote2Cap-DETR.

2.
IEEE Trans Image Process ; 33: 123-133, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38048247

RESUMO

This paper presents a novel method for supervised multi-view representation learning, which projects multiple views into a latent common space while preserving the discrimination and intrinsic structure of each view. Specifically, an apriori discriminant similarity graph is first constructed based on labels and pairwise relationships of multi-view inputs. Then, view-specific networks progressively map inputs to common representations whose affinity approximates the constructed graph. To achieve graph consistency, discrimination, and cross-view invariance, the similarity graph is enforced to meet the following constraints: 1) pairwise relationship should be consistent between the input space and common space for each view; 2) within-class similarity is larger than any between-class similarity for each view; 3) the inter-view samples from the same (or different) classes are mutually similar (or dissimilar). Consequently, the intrinsic structure and discrimination are preserved in the latent common space using an apriori approximation schema. Moreover, we present a sampling strategy to approach a sub-graph sampled from the whole similarity structure instead of approximating the graph of the whole dataset explicitly, thus benefiting lower space complexity and the capability of handling large-scale multi-view datasets. Extensive experiments show the promising performance of our method on five datasets by comparing it with 18 state-of-the-art methods.

3.
Pract Lab Med ; 37: e00342, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37876765

RESUMO

Objectives: In this study, we aimed to establish the trimester-specific RIs of renal function tests (RFTs) in singleton pregnant women and investigate the associations between adverse perinatal outcomes and abnormal renal function laboratory results. Methods: The results of RFTs and the associated medical records were retrieved from 16489 singleton pregnant women who underwent first- and third-trimester prenatal screening and gave a live birth at out institute between August 2018 and December 2019. The RFTs were performed on the automated immunochemistry platform ARCHITECT ci16200 (Abbott Laboratories Ltd, Abbott Park, Illinois, US) in the clinical laboratory of our institute. The nonparametric 2.5th-97.5th percentile intervals and the indirect Hoffmann methods were used to define the trimester-specific RIs. The associations between abnormal RFTs and adverse pregnancy outcomes was assessed statistically by logistic regression. Results: There was no significant difference between the direct observational and the indirect Hoffmann methods in establishing RIs of RFTs. Compared with RFTs in the first trimester, the concentrations of serum BUN and Crea were slightly decreased (p < 0.001), and the serum UA and Cys C levels were significantly elevated in the third trimester (p < 0.001). In the logistic regression analysis, high concentrations of UA, Crea, and Cys C in late pregnancy were associated with an increased risk of postpartum hemorrhage. Meanwhile, early pregnancy UA was associated with a modestly increased risk of GDM, GH, and PE. Conclusion: It is necessary to establish trimester-specific RIs for RFTs, in order to appropriately interpret laboratory results and to identify women with high risks of developing various adverse outcomes.

4.
Ann Med ; 55(2): 2265381, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37824254

RESUMO

BACKGROUND: As folates are essential for embryonic development and growth, it is necessary to accurately determine the levels of folates in plasma and red blood cells (RBCs) for clinical intervention. The aims of this study were to develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantitation of folates in plasma and RBCs and to examine the association between plasma and RBC folate concentrations and gestational diabetes mellitus (GDM), gestational hypertension (GH) and preeclampsia (PE). METHODS: With the in-house developed LC-MS/MS, a retrospective cross-sectional study was conducted. The healthy pregnant women of first- (n = 147), second- (n = 84) and third-trimester (n = 141) or the women diagnosed with GDM (n = 84), GH (n = 58) or PE (n = 23), that were aged between 22 and 46 years old and registered at our institute, were subjected for measurement of folic acid (FA) and 5-methyltetrahydrofolate (5-MTHF), followed by appropriate statistical association analysis. RESULTS: The assay for simultaneous quantitation of FA and 5-MTHF in plasma and RBCs was linear, stable, with imprecision less than 15% and recoveries within ±10%. The lower limits of quantification for FA and 5-MTHF measurement in whole blood were 0.57 and 1.09 nmol/L, and in plasma were 0.5 and 1 nmol/L, respectively. In the association analysis, the patients with lower RBC folate level (<906 nmol/L) presented higher risks of PE development (OR 4.861 [95% CI 1.411-16.505]) by logistic regression and restricted cubic spline (RCS) regression in a nonlinear fashion. In addition, higher level of plasma folates in pregnancy was significantly associated with GH risk but may be protective for the development of GDM. CONCLUSIONS: The in-house developed LC-MS/MS method for folates and metabolites in plasma or RBC showed satisfactory analytical performance for clinical application. Further, the levels of folates and metabolites were diversely associated with GDM, GH and PE development.


Assuntos
Pré-Eclâmpsia , Espectrometria de Massas em Tandem , Feminino , Humanos , Gravidez , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Cromatografia Líquida , Espectrometria de Massas em Tandem/métodos , Estudos Retrospectivos , Estudos Transversais , Ácido Fólico/análise , Eritrócitos/química
5.
Adv Sci (Weinh) ; 10(35): e2302421, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37849221

RESUMO

Dynamically evolving adhesions between cells and extracellular matrix (ECM) transmit time-varying signals that control cytoskeletal dynamics and cell fate. Dynamic cell adhesion and ECM stiffness regulate cellular mechanosensing cooperatively, but it has not previously been possible to characterize their individual effects because of challenges with controlling these factors independently. Therefore, a DNA-driven molecular system is developed wherein the integrin-binding ligand RGD can be reversibly presented and removed to achieve cyclic cell attachment/detachment on substrates of defined stiffness. Using this culture system, it is discovered that cyclic adhesion accelerates F-actin kinetics and nuclear mechanosensing in human mesenchymal stem cells (hMSCs), with the result that hysteresis can completely change how hMSCs transduce ECM stiffness. Results are dramatically different from well-known results for mechanotransduction on static substrates, but are consistent with a mathematical model of F-actin fragments retaining structure following loss of integrin ligation and participating in subsequent repolymerization. These findings suggest that cyclic integrin-mediated adhesion alters the mechanosensing of ECM stiffness by hMSCs through transient, hysteretic memory that is stored in F-actin.


Assuntos
Actinas , Integrinas , Humanos , Adesão Celular/fisiologia , Integrinas/metabolismo , Actinas/análise , Actinas/metabolismo , Mecanotransdução Celular , Matriz Extracelular/metabolismo
6.
Front Endocrinol (Lausanne) ; 14: 1199875, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37560307

RESUMO

Context: Adrenal incidentaloma (AI) is commonly discovered on cross-sectional imaging. Mild autonomous cortisol secretion is the most common functional disorder detected in AI. Objective: To delineate the association between radiological characteristics of benign adrenocortical tumors and hypothalamus-pituitary-adrenal (HPA) axis. Methods: In the study, 494 patients diagnosed with benign unilateral adrenocortical tumors were included. Mild autonomous cortisol secretion (MACS) was diagnosed when cortisol after 1mg-dexamethasone suppression test (1-mg DST) was in the range of 1.8-5ug/dl. Non-functional adrenocortical tumor (NFAT) was diagnosed as cortisol following 1-mg DST less than 1.8ug/dL. We performed Logistics regression and causal mediation analyses, looking for associations between radiological characteristics and the HPA axis. Results: Of 494 patients, 352 (71.3%) with NFAT and 142 (28.7%) with MACS were included. Patients with MACS had a higher tumor diameter, thinner contralateral adrenal gland, and lower plasma ACTH and serum DHEAS than those with NFAT. ACTH (OR 0.978, 0.962-0.993) and tumor diameter (OR 1.857, 95%CI, 1.357-2.540) were independent factors associated with decreased serum DHEAS (all P<0.05). ACTH was also associated with decreased contralateral adrenal diameter significantly (OR 0.973, 95%CI, 0.957-0.988, P=0.001). Causal mediation analysis showed ACTH mediated the effect significantly for the association between 1-mg DST results and DHEAS level (Pmediation<0.001, proportion=22.3%). Meanwhile, we found ACTH mediated 39.7% of the effects of 1-mg DST on contralateral adrenal diameter (Pmediation=0.012). Conclusions: Patients with MACS had thinner contralateral adrenal glands and disturbed HPA axes compared with NFAT. ACTH may partially be involved in mediating the mild autonomous cortisol secretion to DHEAS and the contralateral adrenal gland.


Assuntos
Neoplasias do Córtex Suprarrenal , Adenoma Adrenocortical , Humanos , Hidrocortisona , Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Neoplasias do Córtex Suprarrenal/diagnóstico , Desidroepiandrosterona , Sulfato de Desidroepiandrosterona , Hormônio Adrenocorticotrópico
7.
Front Oncol ; 13: 1137785, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37324005

RESUMO

Background: Peritoneal surface malignancies (PSM) present insidiously and often pose diagnostic challenges. There is a paucity of literature quantifying the frequency and extent of therapeutic delays in PSM and its impact on oncological outcomes. Methods: A review of a prospectively maintained registry of PSM patients undergoing Cytoreductive Surgery and Hyperthermic Intra-peritoneal Chemotherapy (CRS-HIPEC) was conducted. Causes for treatment delays were identified. We evaluate the impact of delayed presentation and treatment delays on oncological outcomes using Cox proportional hazards models. Results: 319 patients underwent CRS-HIPEC over a 6-years duration. 58 patients were eventually included in this study. Mean duration between symptom onset and CRS-HIPEC was 186.0 ± 37.1 days (range 18-1494 days) and mean duration of between patient-reported symptom onset and initial presentation was 56.7 ± 16.8 days. Delayed presentation (> 60 days between symptom onset and presentation) was seen in 20.7% (n=12) of patients and 50.0% (n=29) experienced a significant treatment delay of > 90 days between 1st presentation and CRS-HIPEC. Common causes for treatment delays were healthcare provider-related i.e. delayed or inappropriate referrals (43.1%) and delayed presentation to care (31.0%). Delayed presentation was a significantly associated with poorer disease free survival (DFS) (HR 4.67, 95% CI 1.11-19.69, p=0.036). Conclusion: Delayed presentation and treatment delays are common and may have an impact on oncological outcomes. There is an urgent need to improve patient education and streamline healthcare delivery processes in the management of PSM.

8.
Bioact Mater ; 27: 337-347, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37122898

RESUMO

The abnormal activation of epidermal growth factor receptor (EGFR) drives the development of non-small cell lung cancer (NSCLC). The EGFR-targeting tyrosine kinase inhibitor osimertinib is frequently used to clinically treat NSCLC and exhibits marked efficacy in patients with NSCLC who have an EGFR mutation. However, free osimertinib administration exhibits an inadequate response in vivo, with only ∼3% patients demonstrating a complete clinical response. Consequently, we designed a biomimetic nanoparticle (CMNP@Osi) comprising a polymeric nanoparticle core and tumor cell-derived membrane-coated shell that combines membrane-mediated homologous and molecular targeting for targeted drug delivery, thereby supporting a dual-target strategy for enhancing osimertinib efficacy. After intravenous injection, CMNP@Osi accumulates at tumor sites and displays enhanced uptake into cancer cells based on homologous targeting. Osimertinib is subsequently released into the cytoplasm, where it suppresses the phosphorylation of upstream EGFR and the downstream AKT signaling pathway and inhibits the proliferation of NSCLC cells. Thus, this dual-targeting strategy using a biomimetic nanocarrier can enhance molecular-targeted drug delivery and improve clinical efficacy.

9.
J Clin Endocrinol Metab ; 108(9): 2230-2239, 2023 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-36917004

RESUMO

CONTEXT: Preoperative inflammatory markers, such as the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR), have recently been proposed as prognostic markers in different tumors. However, their predictive values in patients with pheochromocytomas and paragangliomas (PPGLs) are uncertain. OBJECTIVE: This study aimed to investigate the prognostic significance of inflammatory biomarkers in PPGL patients. METHODS: Data from 1247 consecutive PPGL patients between 2002 and 2020 were evaluated. The preoperative inflammatory markers were evaluated. The prognostic roles were identified by X-tile software, Kaplan-Meier curves, and Cox regression models. RESULTS: A total of 728 patients were included in the analysis, with a median follow-up of 63 months (IQR, 31-111 months); 31 individuals died, 28 patients developed metastases, and 12 patients developed recurrence. Our study showed that deaths were observed significantly more frequently in patients with high NLR(≥3.5) and high PLR (≥217.4) than those with low NLR (<3.5) (P = .003) and low PLR (<217.4) (P = .005). Elevated NLR (≥3.5) and elevated PLR (≥217.4) was significantly associated with decreased overall survival (OS) (P = .005), and elevated PLR (≥238.3) was significantly associated with decreased metastasis-free survival (MFS) (P = .021). Cox models illustrated that NLR and PLR were independent prognostic factors for OS, and PLR was an independent prognostic factor for MFS. CONCLUSION: Both elevated NLR and PLR are associated with poor prognosis in PPGLs. They are convenient predictive markers that could be used in daily clinical practice.


Assuntos
Neoplasias das Glândulas Suprarrenais , Paraganglioma , Feocromocitoma , Humanos , Neutrófilos , Prognóstico , Feocromocitoma/diagnóstico , Linfócitos , Plaquetas , Paraganglioma/diagnóstico , Neoplasias das Glândulas Suprarrenais/diagnóstico , Estudos Retrospectivos
10.
Clin Chim Acta ; 541: 117265, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36801269

RESUMO

BACKGROUND: During pregnancy, complex physiological changes take place in the hemostatic system, resulting in a hypercoagulable state. With the established trimester-specific reference intervals (RIs) of the coagulation tests, we investigated the associations between disturbance of hemostasis and adverse pregnant outcomes in a population-based cohort study. METHODS: The first- and third-trimester coagulation tests results were retrieved from 29,328 singleton and 840 twin pregnant women for regular antenatal check-ups from November 30th, 2017 to January 31st, 2021. The trimester-specific RIs for fibrinogen (FIB), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), d-dimer (DD) were estimated using both the direct observational and the indirect Hoffmann methods. The associations between the coagulation tests and the risks of developing pregnancy complications as well as adverse perinatal outcomes were assessed using the logistic regression analysis. RESULTS: Increased FIB, DD and decreased PT, APTT and TT were observed as the gestational age increases in the singleton pregnancy. An enhanced procoagulant state, marked by significant elevation of FIB, DD and reduction of PT, APTT and TT, was observed in the twin pregnancy. The subjects with anormal PT, APTT, TT, DD, tend to have increased risks of developing peri- and postpartum complications such as preterm birth, fetal growth restriction. CONCLUSIONS: The incidence of adverse perinatal outcomes was remarkably associated with the maternal increased levels of FIB, PT, TT, APTT and DD in the third trimester, which may be applied in early identification of women at high risk of adverse outcomes due to coagulopathy.


Assuntos
Hemostáticos , Complicações na Gravidez , Nascimento Prematuro , Feminino , Recém-Nascido , Gravidez , Humanos , Gravidez de Gêmeos , Estudos de Coortes , Testes de Coagulação Sanguínea , Fibrinogênio
11.
IEEE Trans Pattern Anal Mach Intell ; 45(3): 3877-3889, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35617190

RESUMO

In this paper, we study how to make unsupervised cross-modal hashing (CMH) benefit from contrastive learning (CL) by overcoming two challenges. To be exact, i) to address the performance degradation issue caused by binary optimization for hashing, we propose a novel momentum optimizer that performs hashing operation learnable in CL, thus making on-the-shelf deep cross-modal hashing possible. In other words, our method does not involve binary-continuous relaxation like most existing methods, thus enjoying better retrieval performance; ii) to alleviate the influence brought by false-negative pairs (FNPs), we propose a Cross-modal Ranking Learning loss (CRL) which utilizes the discrimination from all instead of only the hard negative pairs, where FNP refers to the within-class pairs that were wrongly treated as negative pairs. Thanks to such a global strategy, CRL endows our method with better performance because CRL will not overuse the FNPs while ignoring the true-negative pairs. To the best of our knowledge, the proposed method could be one of the first successful contrastive hashing methods. To demonstrate the effectiveness of the proposed method, we carry out experiments on five widely-used datasets compared with 13 state-of-the-art methods. The code is available at https://github.com/penghu-cs/UCCH.

12.
IEEE J Biomed Health Inform ; 27(1): 329-338, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36331630

RESUMO

WiFi-based human activity recognition (HAR) has been extensively studied due to its far-reaching applications in health domains, including elderly monitoring, exercise supervision and rehabilitation monitoring, etc. Although existing supervised deep learning techniques have achieved remarkable performances for these tasks, they are however data-hungry and hence are notoriously difficult due to the privacy and incomprehensibility of WiFi-based HAR data. Existing contrastive learning models, mainly designed for computer vision, cannot guarantee their performance on channel state information (CSI) data. To this end, we propose a new dual-stream contrastive learning model that can process and learn the raw WiFi CSI data in a self-supervised manner. More specifically, our proposed method, coined as DualConFi, takes raw WiFI CSI data as input and incorporates channel and temporal streams to learn highly-discriminative spatiotemporal features under a mutual information constraint using unlabeled data. We exhibit the effectiveness of our model on three publicly available CSI data sets in various experiment settings, including linear evaluation, semi-supervised, and transfer learning. We show that DualConFi is able to perform favourably against challenging baselines in each setting. Moreover, by studying the effects of different transform functions on CSI data, we finally verify the effectiveness of highly-discriminative features.


Assuntos
Exercício Físico , Atividades Humanas , Idoso , Humanos , Privacidade
13.
J Mol Biol ; 435(1): 167819, 2023 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-36089055

RESUMO

Cancer has been the leading cause of death due mainly to tumor metastasis. The tumor microenvironment plays a key role in tumor metastasis. As the main stromal cells in tumor microenvironment originated from activated fibroblast, cancer-associated fibroblasts (CAFs) play a major role in promoting tumor metastasis. A promising therapeutic avenue is reprogramming of CAFs into tumor-restraining quiescence state. In this study, we observed that CAF-like active pancreatic stellate cells (PSCs) interact with each other via N-cadherin, a force-sensitive transmembrane receptor. Since N-cadherin ligation mediated mechanotransduction has been reported to restrict integrin mediated signalling, we thus hypothesized that the reprogramming of activated PSCs by mechanical modulation of N-cadherin ligation might be possible. To test this hypothesis, we grafted N-cadherin ligand (HAVDI peptide) onto soft polyethylene glycol hydrogel substrate prior to cell adhesion to mimic cell-cell interaction via N-cadherin ligation. We found that the activated PSCs could be reprogrammed to their original quiescent state when transferred onto the substrate with immobilized HAVDI peptide. These results reveal a key role of mechanosensing by intercellular transmembrane receptor in reprogramming of activated PSCs, and provide a potential way for designing novel therapeutic strategies for cancer treatment.


Assuntos
Caderinas , Reprogramação Celular , Mecanotransdução Celular , Neoplasias , Células Estreladas do Pâncreas , Humanos , Caderinas/química , Linhagem Celular Tumoral , Neoplasias/metabolismo , Neoplasias/patologia , Células Estreladas do Pâncreas/química , Células Estreladas do Pâncreas/citologia , Peptídeos/metabolismo , Microambiente Tumoral
14.
ISA Trans ; 136: 503-524, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36379760

RESUMO

This paper investigates the flight dynamics of the aircraft with wing asymmetric damage and the fault-tolerant control problem to improve the stability and flight quality of damaged aircraft. A high-fidelity wing asymmetric damaged aircraft nonlinear model is developed, as well as the impact of wing asymmetric damage on the physical and aerodynamic properties of the aircraft is also analyzed. The trim strategies for damaged aircraft are investigated to achieve a rapid estimation of trim states after damage occurs. This paper presents a robust cascaded nonlinear fault-tolerant control framework that integrates the incremental nonlinear dynamic inversion control with improved piecewise-constant-based nonlinear L1 adaptive control for the stability control to enhance the stability and tracking performance of the damaged aircraft. Theoretical analysis proves that the presented fault-control structure is robust to disturbances and can decouple rapidity and robustness while guaranteeing steady-state and transient performance. Finally, the hardware-in-the-loop flight control experiment platform is developed to validate the cascaded nonlinear fault-tolerant controller. In the experiment, the proposed controller is verified under wing asymmetric damage and compared with existing methods. Experimental results show that the proposed fault-tolerant control is able to overcome wing asymmetric damage and significantly improve the tracking performance of the damaged aircraft even with 27.2% of the severe damage to the left-wing.

16.
Ann Surg Oncol ; 30(2): 777-789, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36180619

RESUMO

BACKGROUND: Immunonutrition has been shown to reduce hospital stay and postoperative morbidity in patients undergoing gastrointestinal, and head and neck surgery. However, its use has not been demonstrated in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). This study aims to determine the effectiveness of perioperative immunonutrition on patients undergoing CRS-HIPEC in reducing length of hospitalization and postoperative complications. PATIENTS AND METHODS: From April 2017 to December 2018, patients undergoing CRS-HIPEC for peritoneal metastases in a single center were enrolled in a randomized controlled trial. Patients with evidence of intestinal obstruction or with diabetes mellitus were excluded. Patients were randomly assigned in a 1:1 fashion to receive perioperative oral immunonutrition or standard nutritional feeds. Length of hospital stay and rates of wound infection and complications were recorded and compared between the two groups in an intention-to-treat manner. RESULTS: A total of 62 patients were recruited and randomized into two groups. Compliance to nutritional feeds in the preoperative period was significantly higher in the standard nutrition group (95.2% versus 75.4%, p = 0.004). There was no difference in postoperative compliance rates. Length of hospital stay and rates of wound infection and postoperative complications were higher in the standard nutrition group when compared with patients on immunonutrition (15.5 versus 11.1 days, p = 0.186; 19% versus 9.7%, p = 0.473; 16% versus 9.7%, p = 0.653; respectively). CONCLUSIONS: Patients undergoing CRS-HIPEC who received perioperative immunonutrition had shorter hospitalization and less wound infections and postoperative complications, although the differences with the standard nutrition group were not statistically significant. Potential benefits of perioperative immunonutrition need to be further evaluated in larger studies.


Assuntos
Hipertermia Induzida , Neoplasias Peritoneais , Infecção dos Ferimentos , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Dieta de Imunonutrição , Neoplasias Peritoneais/secundário , Hipertermia Induzida/efeitos adversos , Complicações Pós-Operatórias/etiologia , Infecção dos Ferimentos/complicações
17.
Pest Manag Sci ; 79(1): 206-215, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36129128

RESUMO

BACKGROUND: Pesticides are extensively applied globally. Pesticide residues induce calamitous effects on the environment and untargeted organisms. Public concerns for the safety of freshwater organisms and the challenges posed by aquatic contaminants remain high. In the present study, the acute toxicity of avermectins (AVMs) to the crayfish, Procambarus clarkii was evaluated. We also evaluated the potential effects of AVM on the biochemical and transcriptomic status of the hepatopancreas and gastrointestinal tract in P. clarkii. RESULTS: The 24, 48, 72, 96 h median lethal concentrations (LC50 ) of AVM on crayfish were 2.626, 1.162, 0.723, 0.566 mg L-1 , respectively. The crayfish were then exposed to 0.65 mg L-1 of AVM for 96 h. AVM significantly altered biochemical parameters including AChE and CAT activities in the hepatopancreas, and AChE, SOD and Na + -K + -ATPase activities in the gastrointestinal tract at several time points. Furthermore, transcriptomic analysis identified 953 and 1851 differentially-expressed genes (DEGs) in the hepatopancreas and gastrointestinal tract, respectively. KEGG enrichment showed that the gene expression profiles of the hepatopancreas and gastrointestinal tract were distinct from each other. The DEGs in the hepatopancreas were mostly enriched with stress-response pathways, while the majority of the DEGs in the gastrointestinal tract belonged to metabolism-related pathways. CONCLUSION: We demonstrated that the AVM induced acute toxicity, oxidative stress, osmoregulation disturbance, neurotoxicity and transcriptome imbalance in crayfish. These findings unraveled the detrimental effects of AVMs exposure on crayfish. © 2022 Society of Chemical Industry.

18.
J Mol Recognit ; 35(12): e2986, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36326001

RESUMO

The Yes-associated protein-1 (YAP1) is an essential regulator of human Hippo signaling pathway and functions through interaction with TEA domain-4 (TEAD4) transcription factor involved in the tumorigenesis of nasopharyngeal cancer. Previously, a parallel helix-helix interaction (PHHI) was identified as the key hotspot at YAP1-TEAD4 complex interface and has been exploited as an attractive druggable target to disrupt the complex. In this study, we investigated a roughly orthogonal cation-π-π stacking system across the crystal PHHI packing interface by integrating computational modeling and binding assay, which forms between one YAP1 helical residue Phe69 and two TEAD4 helical residues Phe373/Lys376. A synergistic effect between cation-π and π-π interactions was observed; they separately represent two wings of the stacking system. The π-electron is primarily responsible for the synergistic effect. Combination between diverse aromatic/charged amino acids. as well as neutral alanine on the cation-π-π stacking, revealed that the presence of aromatic tryptophan and charged arginine at, respectively, the residues 373 and 376 of TEAD4 helix can considerably improve PHHI binding affinity by ~6-fold, whereas neutral alanine substitution on each residue and on both would reduce the affinity significantly, confirming a strong synergistic effect involved in the roughly orthogonal cation-π-π stacking system at YAP1-TEAD4 PHHI interface.


Assuntos
Neoplasias Nasofaríngeas , Fatores de Transcrição de Domínio TEA , Humanos , Proteínas de Ligação a DNA/química , Carcinoma Nasofaríngeo , Proteínas Musculares/química , Proteínas Musculares/metabolismo , Fatores de Transcrição/metabolismo , Cátions/química , Alanina
19.
Pleura Peritoneum ; 7(2): 63-75, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35812011

RESUMO

Objectives: Various studies have shown that good quality of life (QoL) can be achieved after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). There is prognostic value of baseline QoL in post-operative outcome in Western setting. Our prospective study aims to validate these observations and elucidate clinical factors that predict poorer QoL in Asian peritoneal carcinomatosis patients. Methods: European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire was administered to patients before CRS and HIPEC and thereafter at 3, 6 and 12 months. Results: A total of 151 patients underwent 155 surgeries. Four hundred and seventy two questionnaires were completed. Median disease-free survival (DFS) was 16.5 months. Three year DFS and overall survival (OS) were 24.0% and 73.0% respectively. Post-operative global health status significantly increased at 3, 6 and 12 months. The decreases in functional scales recovered to baseline by 1-year post-surgery. Peritoneal carcinomatosis index (PCI), presence of stoma, peritonectomy duration, death within one year, post-operative complication and length of SICU stay negatively influenced QoL. Complication rates were higher in patients with lower global health status, physical and role functioning scores and higher symptom summary scores at baseline. Lower social functioning score, and higher pain, dyspnoea and symptom summary scores at baseline were significantly associated with poorer OS. Conclusions: Various clinical factors can help us predict a patient's QoL after surgery. Several baseline factors were also able to predict morbidity and survival. Going forward, we can use these factors to help us better select patients who will have a greater benefit from CRS and HIPEC.

20.
Cancers (Basel) ; 14(13)2022 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-35804951

RESUMO

Background: The performance of MRI versus CT in the detection and evaluation of peritoneal surface malignancies (PSM) remains unclear in the current literature. Our study is the first prospective study in an Asian center comparing the two imaging modalities, validated against intra-operative findings. Methods: A total of 36 patients with PSM eligible for CRS-HIPEC underwent both MRI and CT scans up to 6 weeks before the operation. The scans were assessed for the presence and distribution of PSM and scored using the peritoneal cancer index (PCI), which were compared against PCI determined at surgery. Results: Both MRI and CT were 100% sensitive and specific in detecting the overall presence of PSM. Across all peritoneal regions, the sensitivity and specificity for PSM detection was 49.1% and 93.0% for MRI, compared to 47.8% and 95.1% for CT (p = 0.76). MRI was more sensitive than CT for small bowel disease, although the difference did not reach statistical significance. Comparing PCI on imaging with intra-operative PCI, the mean difference was found to be −3.4 ± 5.4 (p < 0.01) for MRI, and −3.9 ± 4.1 (p < 0.01) for CT. The correlation between imaging and intra-operative PCI was poor, with a concordance coefficient of 0.76 and 0.79 for MRI and CT, respectively. Within individual peritoneal regions, there was also poor agreement between imaging and intra-operative PCI for both modalities, other than in regions 1 and 3. Conclusion: MRI and CT are comparable in the detection and evaluation of PSM. While sensitive in the overall detection of PSM, they are likely to underestimate the true disease burden.

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