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Glioblastoma (GBM), a highly malignant and lethal brain tumor, is characterized by diffuse invasion into the brain and chemo-radiotherapy resistance resulting in poor prognosis. In this study, we examined the involvement of the cell adhesion molecule CD146/MCAM in regulating GBM aggressiveness. Analyses of GBM transcript expression databases revealed correlations of elevated CD146 levels with higher glioma grades, IDH-wildtype and unmethylated MGMT phenotypes, poor response to chemo-radiotherapy and worse overall survival. In a panel of GBM stem cells (GSCs) variable expression levels of CD146 were detected, which strongly increased upon adherent growth. CD146 was linked with mesenchymal transition since expression increased in TGF-ß-treated U-87MG cells. Ectopic overexpression of CD146/GFP in GG16 cells enhanced the mesenchymal phenotype and resulted in increased cell invasion. Conversely, GSC23-CD146 knockouts had decreased mesenchymal marker expression and reduced cell invasion in transwell and GBM-cortical assembloid assays. Moreover, using GSC23 xenografted zebrafish, we found that CD146 depletion resulted in more compact delineated tumor formation and reduced tumor cell dissemination. Stem cell marker expression and neurosphere formation assays showed that CD146 increased the stem cell potential of GSCs. Furthermore, CD146 mediated radioresistance by stimulating cell survival signaling through suppression of p53 expression and activation of NF-κB. Interestingly, CD146 was also identified as an inducer of the oncogenic Yes-associated protein (YAP). In conclusion, CD146 carries out various pro-tumorigenic roles in GBM involving its cell surface receptor function, which include the stimulation of mesenchymal and invasive properties, stemness, and radiotherapy resistance, thus providing an interesting target for therapy.
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Neoplasias Encefálicas , Glioblastoma , Glioma , Animais , Neoplasias Encefálicas/patologia , Antígeno CD146/genética , Antígeno CD146/metabolismo , Glioblastoma/patologia , Glioma/patologia , Peixe-Zebra/metabolismoRESUMO
With the increasing popularity of electric vehicles, cable-driven serial manipulators have been applied in auto-charging processes for electric vehicles. To ensure the safety of the physical vehicle-robot interaction in this scenario, this paper presents a model-independent collision localization and classification method for cable-driven serial manipulators. First, based on the dynamic characteristics of the manipulator, data sets of terminal collision are constructed. In contrast to utilizing signals based on torque sensors, our data sets comprise the vibration signals of a specific compensator. Then, the collected data sets are applied to construct and train our collision localization and classification model, which consists of a double-layer CNN and an SVM. Compared to previous works, the proposed method can extract features without manual intervention and can deal with collision when the contact surface is irregular. Furthermore, the proposed method is able to generate the location and classification of the collision at the same time. The simulated experiment results show the validity of the proposed collision localization and classification method, with promising prediction accuracy.
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Máquina de Vetores de SuporteRESUMO
With the gradual maturity of driverless and automatic parking technologies, electric vehicle charging has been gradually developing in the direction of automation. However, the pose calculation of the charging port (CP) is an important part of realizing automatic charging, and it represents a problem that needs to be solved urgently. To address this problem, this paper proposes a set of efficient and accurate methods for determining the pose of an electric vehicle CP, which mainly includes the search and aiming phases. In the search phase, the feature circle algorithm is used to fit the ellipse information to obtain the pixel coordinates of the feature point. In the aiming phase, contour matching and logarithmic evaluation indicators are used in the cluster template matching algorithm (CTMA) proposed in this paper to obtain the matching position. Based on the image deformation rate and zoom rates, a matching template is established to realize the fast and accurate matching of textureless circular features and complex light fields. The EPnP algorithm is employed to obtain the pose information, and an AUBO-i5 robot is used to complete the charging gun insertion. The results show that the average CP positioning errors (x, y, z, Rx, Ry, and Rz) of the proposed algorithm are 0.65 mm, 0.84 mm, 1.24 mm, 1.11 degrees, 0.95 degrees, and 0.55 degrees. Further, the efficiency of the positioning method is improved by 510.4% and the comprehensive plug-in success rate is 95%. Therefore, the proposed CTMA in this paper can efficiently and accurately identify the CP while meeting the actual plug-in requirements.
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The structure of the cable-driven serial manipulator (CDSM) is more complex than that of the cable-driven parallel manipulator (CDPM), resulting in higher model complexity and stronger structural and parametric uncertainties. These drawbacks challenge the stable trajectory-tracking control of a CDSM. To circumvent these drawbacks, this paper proposes a robust adaptive controller for an n-degree-of-freedom (DOF) CDSM actuated by m cables. First, two high-level controllers are designed to track the joint trajectory under two scenarios, namely known and unknown upper bounds of uncertainties. The controllers include an adaptive feedforward term based on inverse dynamics and a robust control term compensating for the uncertainties. Second, the independence of control gains from the upper bound of uncertainties and the inclusion of the joint viscous friction coefficient into the dynamic parameter vector are realised. Then, a low-level controller is designed for the task of tracking the cable tension trajectory. The system stability is analysed using the Lyapunov method. Finally, the validity and effectiveness of the proposed controllers are verified by experimenting with a three-DOF six-cable CDSM. In addition, a comparative experiment with the classical proportional-integral-derivative (PID) controller is carried out.
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Resistance to tamoxifen remains a prominent conundrum in the therapy of hormone-sensitive breast cancer. Also, the molecular underpinnings leading to tamoxifen resistance remain unclear. In the present study, we utilized the Gene Expression Omnibus database to identify that SOX11 might exert a pivotal function in conferring tamoxifen resistance of breast cancer. SOX11 was found to be markedly upregulated at both the messenger RNA and protein levels in established MCF-7-Tam-R cells compared to the parental counterparts. Moreover, SOX11 was able to activate the transcription of slug via binding to its promoter, resulting in promoting the progress of epithelial-to-mesenchymal transition and suppressing the expression of ESR1. Downregulating SOX11 expression can restore the sensitivity to 4-hydroxytamoxifen in MCF-7-Tam-R cells. Survival analysis from large sample datasets indicated that SOX11 was closely related to poorer survival in patients with breast cancer. These findings suggest a novel feature of SOX11 in contributing to tamoxifen resistance. Hence, targeting SOX11 could be a potential therapeutic strategy to tackle tamoxifen resistance in breast cancer.
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Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Fatores de Transcrição SOXC/genética , Fatores de Transcrição SOXC/metabolismo , Fatores de Transcrição da Família Snail/genética , Tamoxifeno/farmacologia , Antineoplásicos Hormonais/farmacologia , Neoplasias da Mama/genética , Resistencia a Medicamentos Antineoplásicos/genética , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Modelos Biológicos , Prognóstico , Regiões Promotoras Genéticas , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Neoplásico/genética , RNA Neoplásico/metabolismo , Fatores de Transcrição SOXC/antagonistas & inibidores , Fatores de Transcrição da Família Snail/metabolismo , Regulação para CimaRESUMO
Resistance to chemotherapy continues to be a critical issue in the clinical therapy of triple-negative breast cancer (TNBC). Epithelial-mesenchymal transition (EMT) is thought to contribute to chemoresistance in several cancer types, including breast cancer. Identification of the key signaling pathway that regulates the EMT program and contributes to chemoresistance in TNBC will provide a novel strategy to overcome chemoresistance in this subtype of cancer. Herein, we demonstrate that Notch1 positively associates with melanoma cell adhesion molecule (MCAM), a unique EMT activator, in TNBC tissue samples both at mRNA and protein levels. High expression of Notch1 and MCAM both predicts a poor survival in basal-like/TNBC patients, particularly in those treated with chemotherapy. The expression of Notch1 and MCAM in MDA-MB-231 cells gradually increases in a time-dependent manner when exposing to low dose cisplatin. Moreover, the expressions of Notch1 and MCAM in cisplatin-resistant MDA-MB-231 cells are significantly higher than wild-type counterparts. Notch1 promotes EMT and chemoresistance, as well as invasion and proliferation of TNBC cells via direct activating MCAM promoter. Inhibition of Notch1 significantly downregulates MCAM expression, resulting in the reversion of EMT and chemoresistance to cisplatin in TNBC cells. Our study reveals the regulatory mechanism of the Notch1 pathway and MCAM in TNBC and suggesting that targeting the Notch1/MCAM axis, in conjunction with conventional chemotherapies, might be a potential avenue to enhance the therapeutic efficacy for patients with TNBC.
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Cisplatino/administração & dosagem , RNA Interferente Pequeno/administração & dosagem , Receptor Notch1/genética , Receptor Notch1/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Antígeno CD146/genética , Antígeno CD146/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Células MCF-7 , Camundongos , Prognóstico , Regiões Promotoras Genéticas , RNA Interferente Pequeno/farmacologia , Análise de Sobrevida , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Regulação para Cima/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Early prediction of response to neoadjuvant chemotherapy (NAC) is critical in choosing appropriate chemotherapeutic regimen for patients with locally advanced breast cancer. Herein, we sought to identify potential biomarkers to predict the response to neoadjuvant chemotherapy for breast cancer patients. METHODS: Three genomic profiles acquired by microarray analysis from subjects with or without residual tumors after NAC downloaded from the GEO database were used to screen the differentially expressed genes (DEGs). An array of public databases, including ONCOMINE, cBioportal, Breast Cancer Gene Expression Miner v4.0, and the Kaplan Meir-plotter, etc., were used to evaluate the potential functions, related signaling pathway, as well as prognostic values of FABP7 in breast cancer. Anti-cancer drug sensitivity assay, real-time PCR, flow cytometry and western-blotting assays were used to investigate the function of FABP7 in breast cancer cells and examine the relevant mechanism. RESULTS: Two differentially expressed genes, including FABP7 and ESR1, were identified to be potential indicators of response to anthracycline and taxanes for breast cancer. FABP7 was associated with better chemotherapeutic response, while ESR1 was associated with poorer chemotherapeutic effectiveness. Generally, the expression of FABP7 was significantly lower in breast cancer than normal tissue samples. FABP7 mainly high expressed in ER-negative breast tumor and might regulate cell cycle to enhance chemosensitivity. Moreover, elevated FABP7 expression increased the percentage of cells at both S and G2/M phase in MDA-MB-231-ADR cells, and decreased the percentage of cells at G0/G1 phase, as compared to control group. Western-blotting results showed that elevated FABP7 expression could increase Skp2 expression, while decrease Cdh1 and p27kip1 expression in MDA-MB-231-ADR cells. In addition, FABP7 was correlated to longer recurrence-free survival (RFS) in BC patients with ER-negative subtype of BC treated with chemotherapy. CONCLUSION: FABP7 is a potential favorable biomarker and predicts better response to NAC in breast cancer patients. Future study on the predictive value and detail molecular mechanisms of FABP7 in contribution to chemosensitivity in breast cancer is warranted.
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The unique structure and mechanical properties of syringe-injectable mesh electronics have enabled seamless tissue integration and stable chronic recording of the activities of the same neurons on a year scale. Here, we report studies of a series of structural and mechanical mesh electronics design variations that allow injection using needles at least 4-fold smaller than those previously reported to minimize the footprint during injection of the electronics in soft matter and tissue. Characterization of new ultraflexible two-dimensional (2D) and one-dimensional (1D) probes has demonstrated reproducible injection of the newly developed mesh electronics designs via needles as small as 100 µm in inner diameter (ID) with reduced injection volumes. In vitro hydrogel and in vivo mouse brain studies have shown that ultraflexible 2D and 1D probes maintain their structural integrity and conformation post-injection after being transferred through the reduced diameter needles. In addition, analysis of the variation of the post-injection mesh cross sections suggests a smaller degree of tissue deformation and relaxation with decreasing needle diameters. The capability to implement rational design for mesh electronic probes that can be delivered via much smaller diameter needles should open up new opportunities for integration of electronics with tissue and soft matter in fundamental and translational studies.
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Materiais Biomiméticos/administração & dosagem , Eletrônica Médica/instrumentação , Maleabilidade , Animais , Materiais Biomiméticos/química , Encéfalo/fisiologia , Desenho de Equipamento , Injeções , Camundongos , Agulhas , Neurônios/fisiologia , Próteses e ImplantesRESUMO
A mid-infrared (mid-IR) sensor chip was demonstrated for volatile organic compound (VOC) detection. The sensor consisted of As2Se3 optical waveguides built by microelectronic fabrication processes. The VOC sensing performance was characterized by measuring acetone and ethanol vapors at their characteristic C-H absorption from λ = 3.40 to 3.50 µm. Continuous VOC detection with <5 s response time was achieved by measuring the intensity attenuation of the waveguide mode. The miniaturized noninvasive VOC sensor can be applied to breath analysis and environmental toxin monitoring.
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Arsenicais/química , Compostos de Selênio/química , Compostos Orgânicos Voláteis/análise , Acetona/análise , Etanol/análise , Espectrofotometria Infravermelho/instrumentação , Espectrofotometria Infravermelho/métodosRESUMO
A mid-infrared (mid-IR) spectrometer for label-free on-chip chemical sensing was developed using an engineered nanofluidic channel consisting of a Si-liquid-Si slot-structure. Utilizing the large refractive index contrast (Δn â¼ 2) between the liquid core of the waveguide and the Si cladding, a broadband mid-IR lightwave can be efficiently guided and confined within a nanofluidic capillary (≤100 nm wide). The optical-field enhancement, together with the direct interaction between the probe light and the analyte, increased the sensitivity for chemical detection by 50 times when compared to evanescent-wave sensing. This spectrometer distinguished several common organic liquids (e.g., n-bromohexane, toluene, isopropanol) accurately and could determine the ratio of chemical species (e.g., acetonitrile and ethanol) at low concentration (<5 µL/mL) in a mixture through spectral scanning over their characteristic absorption peaks in the mid-IR regime. The combination of CMOS-compatible planar mid-IR microphotonics, and a high-throughput nanofluidic sensor system, provides a unique platform for chemical detection.
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Técnicas de Química Analítica/instrumentação , Análise em Microsséries/instrumentação , Microquímica/instrumentação , Técnicas Analíticas Microfluídicas/instrumentação , Nanotecnologia/instrumentação , Espectrofotometria Infravermelho/instrumentação , Ressonância de Plasmônio de Superfície/instrumentação , Desenho de Equipamento , Análise de Falha de Equipamento , Coloração e RotulagemRESUMO
Perina nuda (Lepidoptera: Lymantriidae) is a serious pest of banyan trees (Ficus spp.), which is distributed in South China, but little is known about the host preference on the different banyan tree species. To address this gap, we conducted experiments to investigate larval feeding preferences, assessing the impact of feeding experience in both choice and no-choice conditions. Fifth and sixth instars were exposed to 4 banyan species, and food intake, feeding area, and relative ingestion index were measured. Our findings reveal that Ficus concinna was the preferred host of fifth instars in choice tests, while sixth instars exhibited a preference for this host in no-choice tests. In contrast, fifth instars did not display a significant preference for any of the 4 species in no-choice tests. However, sixth instars fed on F. microcarpa, F. altissima, and F. concinna continued to exhibit a preference for the original host. These observations indicate that larval feeding preference changes with instar, and feeding experience contributes to a preference for the original host. Consequently, the feeding preference of P. nuda larvae is influenced by multiple factors, including instar and previous feeding experience. These findings enhance our understanding of P. nuda's ecological interactions and its potential impact on various banyan tree species.
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Ficus , Lepidópteros , Mariposas , Animais , Larva , Comportamento Alimentar , Plantas , ÁrvoresRESUMO
Morphological attributes and chemical composition of host plants shape growth and development of phytophagous insects via influences on their behavior and physiological processes. This research delves into the relationship between Eriogyna pyretorum and various host plants through studuying how feeding on different host tree species affect growth, development, and physiological enzyme activities. We examined E. pyretorum response to three distinct host plants: Camphora officinarum, Liquidambar formosana and Pterocarya stenoptera. Notably, larvae feeding on C. officinarum and L. formosana displayed accelerated development, increased pupal length, and higher survival rates compared to those on P. stenoptera. This underlines the pivotal role of host plant selection in shaping the E. pyretorum's life cycle. The activities of a-amylase, lipase and protective enzymes were the highest in larvae fed on the most suitable host L. formosana which indicated that the increase of these enzyme activities was closely related to growth and development. Furthermore, our investigation revealed a relationship between enzymatic activities and host plants. Digestive enzymes, protective enzymes, and detoxifying enzymes exhibited substantial variations contingent upon the ingested host plant. Moreover, the total phenolics content in the host plant leaves manifested a noteworthy positive correlation with catalase and lipase activities. In contrast, a marked negative correlation emerged with glutathione S-transferase and α-amylase activities. The total developmental duration of larvae exhibited a significant positive correlation with the activities of GST and CarE. The survival rate of larvae showed a significant positive correlation with CYP450. These observations underscore the insect's remarkable adaptability in orchestrating metabolic processes in accordance with available nutritional resources. This study highlights the interplay between E. pyretorum and its host plants, offering novel insights into how different vegetation types influence growth, development, and physiological responses. These findings contribute to a deeper comprehension of insect-plant interactions, with potential applications in pest management and ecological conservation.
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Larva , Animais , Larva/crescimento & desenvolvimento , Larva/enzimologia , Folhas de Planta/parasitologia , Folhas de Planta/metabolismo , Mariposas/enzimologia , Mariposas/crescimento & desenvolvimento , Mariposas/fisiologiaRESUMO
The incidence rate and mortality rate of cardiovascular disease rank first in the world. It is associated with various high-risk factors, and there is no single cause. Epigenetic modifications, such as DNA methylation or histone modification, actively participate in the initiation and development of cardiovascular diseases. Histone lysine methylation is a type of histone post-translational modification. The human Jumonji C domain (JMJD) protein family consists of more than 30 members. JMJD proteins participate in many key nuclear processes and play a key role in the specific regulation of gene expression, DNA damage and repair, and DNA replication. Importantly, increasing evidence shows that JMJD proteins are abnormally expressed in cardiovascular diseases, which may be a potential mechanism for the occurrence and development of these diseases. Here, we discuss the key roles of JMJD proteins in various common cardiovascular diseases. This includes histone lysine demethylase, which has been studied in depth, and less-studied JMJD members. Furthermore, we focus on the epigenetic changes induced by each JMJD member, summarize recent research progress, and evaluate their relationship with cardiovascular diseases and therapeutic potential.
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Doenças Cardiovasculares , Humanos , Histona Desmetilases , Histonas , Cognição , Dano ao DNARESUMO
RNA-binding proteins (RBPs) refer to a class of proteins that participate in alternative splicing, RNA stability, polyadenylation, localization and translation of RNAs, thus regulating gene expression in post-transcriptional manner. Dysregulation of RNA-RBP interaction contributes to various diseases, including cancer. In breast cancer, disorders in RBP expression and function influence the biological characteristics of tumor cells. Targeting RBPs has fostered the development of innovative therapies for breast cancer. However, the RBP-related mechanisms in breast cancer are not completely clear. In this review, we summarize the regulatory mechanisms of RBPs and their signaling crosstalk in breast cancer. Specifically, we emphasize the potential of certain RBPs as prognostic factors due to their effects on proliferation, invasion, apoptosis, and therapy resistance of breast cancer cells. Most importantly, we present a comprehensive overview of the latest RBP-related therapeutic strategies and novel therapeutic targets that have proven to be useful in the treatment of breast cancer.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Proteínas de Ligação a RNA/genéticaRESUMO
Trastuzumab (Tmab) targeted therapy or its combination with chemotherapy is normally insufficient to elicit a comprehensive therapeutic response owing to the inherent or acquired drug resistance and systemic toxicity observed in highly invasive HER2-positive breast cancer. In this study, we propose a novel approach that integrates photothermal therapy (PTT) with targeted therapy and chemotherapy, thereby achieving additive or synergistic therapeutic outcomes. We utilize PEGylated two-dimensional black phosphorus (2D BP) as a nanoplatform and photothermal agent to load chemotherapeutic drug mitoxantrone (MTO) and conjugate with Tmab (BP-PEG-MTO-Tmab). The in vitro and in vivo experiments demonstrated that the HER2-targeting BP-PEG-MTO-Tmab complexes exhibited desirable biocompatibility, safety and enhanced cancer cell uptake efficiency, resulting in increased accumulation and prolonged retention of BP and MTO within tumors. Consequently, the complex improved photothermal and chemotherapy treatment efficacy in HER2-positive cells in vitro and a subcutaneous tumor model in vivo, while minimized harm to normal cells and showed desirable organ compatibility. Collectively, our study provides compelling evidence for the remarkable efficacy of targeted and synergistic chemo-photothermal therapy utilizing all-in-one nanoparticles as a delivery system for BP and chemotherapeutic drug in HER2-positive breast cancer.
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Introduction: It is essential to protect cancer patients from contracting COVID-19 through vaccination. A majority of cancer patients are recommended by international health authorities to take up the vaccines. COVID-19 vaccine refusal among cancer patients during the pandemic period is under-researched. This study investigated factors of vaccine refusal based on the Health Belief Model (HBM). Methods: A cross-sectional study was conducted among female breast cancer patients, male/female thyroid cancer patients, and gynecological cancer patients in Shantou, China from April to August 2022 (n = 1,115). Multinomial logistic regression analysis adjusted for socio-demographics was conducted to test factors of COVID-19. Adjusted odds ratios of the two models comparing vaccine refusal vs. "vaccine non-refusal" and vaccine refusal vs. ever-vaccination were derived and presented. Results: Of all the participants, the prevalence of vaccine refusal, "vaccine non-refusal," and ever-vaccination was 25.9, 22.2, and 51.8%, respectively. In both multinomial logistic regression models, significant factors of vaccine refusal included socio-demographics (age, education level, employment status, monthly household income, cancer type, duration since cancer diagnosis, current treatment status) and some vaccine-related HBM (perceived benefits, perceived barriers, cue to action, and self-efficacy). Perceived severity of COVID-19 was significant only in the vaccine refusal vs. ever-vaccination model. In neither model, perceived susceptibility to contract COVID-19 was statistically significant. Conclusion: About » of the participants expressed vaccine refusal. Interventions are warranted. Future longitudinal studies are needed to verify this study's findings. Pilot interventions should also be launched to test effectiveness of interventions modifying the significant HBM factors found in this study.
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Neoplasias da Mama , COVID-19 , Humanos , Feminino , Masculino , Vacinas contra COVID-19 , Prevalência , Estudos Transversais , COVID-19/epidemiologia , COVID-19/prevenção & controle , China/epidemiologia , Modelo de Crenças de SaúdeRESUMO
Background: Short videos on social media are playing an increasingly important role in cancer health education today. It is important to explore how the actual communication effect of health videos and the knowledge absorption of users are influenced by different factors of the video creation process. Objective: The objective of our study is to access the factors influencing breast cancer health education through short videos on efficiency and quality. Methods: Three pairs of videos about breast health were created and participants completed questionnaires before and after watching the videos. A paired t-test was used to analyze within-group change scores. RM-ANOVA was used to assess the relationship between the pretest, posttest, and three variables. Results: Watching short videos can significantly increase viewers' knowledge of related health topics (p < 0.05). The viewers' concentration level while watching was significantly higher for the video with background music (BGM) than for the video without BGM (p = 0.006). The viewers' willingness to share was significantly higher for the video with a progress bar than for the video without a progress bar (p = 0.02). Using an interpreter wearing a doctor's uniform instead of casual wear and setting a progress bar can significantly improve the efficiency of knowledge absorption (p < 0.05). Conclusion: A uniformed interpreter, BGM and a progress bar are factors influencing the efficiency of short health videos. They can be applied in video making to explore better ways of promoting cancer health education in the new mobile Internet environment.
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Neoplasias da Mama , Mídias Sociais , Feminino , Humanos , Atitude , Grupos Controle , AlfabetizaçãoRESUMO
Hereditary protein S deficiency is a risk factor which may predispose patients to venous thrombosis. Deep venous thrombosis of the lower extremities can result in painful congestion, while the presence of mesenteric venous thrombosis (MVT) can cause abdominal emergencies. We herein report a protein S-deficient patient presenting with acute portomesenteric venous thrombosis. Early management using anticoagulant therapy was initially successful. However, the subsequent bowel stricture resulting from the ischemic insult was further managed with a surgical bypass. The patient was kept on long-term thrombophylaxis. The treatment strategy for MVT with bowel ischemia has evolved from aggressive portomesenteric thrombectomy with resection of the involved bowel, to conservative anticoagulation to recanalize thrombotic mesenteric veins with bowel preservation. Surgical intervention is reserved for transmural necrosis or bowel perforation. The perioperative thrombophylaxis of inherited thrombophilic patients is also important for preventing further thromboembolic events.
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Anticoagulantes/uso terapêutico , Oclusão Vascular Mesentérica/tratamento farmacológico , Deficiência de Proteína S/complicações , Trombose Venosa/tratamento farmacológico , Doença Aguda , Adulto , Humanos , Jejuno/irrigação sanguínea , Jejuno/cirurgia , Masculino , Oclusão Vascular Mesentérica/diagnóstico , Oclusão Vascular Mesentérica/etiologia , Veias Mesentéricas , Veia Porta , Trombose Venosa/diagnóstico , Trombose Venosa/etiologiaRESUMO
The drug development pipeline involves several stages including in vitro assays, in vivo assays, and clinical trials. For candidate selection, it is important to consider that a compound will successfully pass through these stages. Using graph neural networks, we developed three subdivisional models to individually predict the capacity of a compound to enter in vivo testing, clinical trials, and market approval stages. Furthermore, we proposed a strategy combing both active learning and ensemble learning to improve the quality of the models. The models achieved satisfactory performance in the internal test datasets and four self-collected external test datasets. We also employed the models as a general index to make an evaluation on a widely known benchmark dataset DEKOIS 2.0, and surprisingly found a powerful ability on virtual screening tasks. Our model system (termed as miDruglikeness) provides a comprehensive drug-likeness prediction tool for drug discovery and development.