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Objectives: This study used repeated cross-sectional data from three national surveys in Vietnam to determine tobacco smoking prevalence from 2010 to 2020 and disparities among demographic and socioeconomic groups. Methods: Tobacco smoking temporal trends were estimated for individuals aged 15 and over and stratified by demographic and socioeconomic status (SES). Prevalence estimates used survey weights and 95% confidence intervals. Logistic regression models adjusted for survey sample characteristics across time were used to examine trends. Results: Tobacco smoking prevalence dropped from 23.8% in 2010 to 22.5% in 2015 and 20.8% in 2020. The adjusted OR for 2015 compared to 2010 was 0.87, and for 2020 compared to 2010 was 0.69. Smoking decreased less for employed individuals than unemployed individuals in 2020 compared to 2010. Smoking was higher in the lower SES group in all 3 years. Higher-SES households have seen a decade-long drop in tobacco use. Conclusion: This prevalence remained constant in lower SES households. This highlights the need for targeted interventions to address the specific challenges faced by lower-SES smokers and emphasizes the importance of further research to inform effective policies.
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Fumar Tabaco , Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Estudos Transversais , Fumar Tabaco/epidemiologia , Fumar Tabaco/tendências , Vietnã/epidemiologia , PrevalênciaRESUMO
Genomes carry the genetic blueprint of all living organisms. Their organization requires strong condensation as well as carefully regulated accessibility to specific genes for proper functioning of their hosts. The study of the structure and dynamics of the proteins that organize the genome has benefited tremendously from the development of single-molecule force spectroscopy techniques that allow for real-time, nanometer accuracy measurements of the compaction of DNA and manipulation with pico-Newton scale forces. Magnetic tweezers, in particular, have the unique ability to complement such force spectroscopy with the control over the linking number of the DNA molecule, which plays an important role when DNA-organizing proteins form or release wraps, loops, and bends in DNA. Here, we describe all the necessary steps to prepare DNA substrates for magnetic tweezers experiments, assemble flow cells, tether DNA to a magnetic bead inside a flow cell, and manipulate and record the extension of such DNA tethers. Furthermore, we explain how mechanical parameters of nucleoprotein filaments can be extracted from the data.
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DNA , Imagem Individual de Molécula , DNA/química , DNA/genética , Imagem Individual de Molécula/métodos , Microscopia de Força Atômica/métodos , Magnetismo , Conformação de Ácido Nucleico , Pinças ÓpticasRESUMO
OBJECTIVES: This study aims to determine the malnutrition status among Vietnamese patients newly diagnosed with gastric cancer (GC). BACKGROUND: GC remains the top rank of common and deadly diseases. With limited clinical manifestation, most GC patients were diagnosed at late stages when tumor is not radically resected. Malnutrition was associated with poor prognosis of GC, such as prolonged hospitalization, limited treatment efficacy and low survival rate. METHODS: The cross-sectional descriptive study recruited 77 patients newly diagnosed with GC and 90 healthy individuals (HC). The data used for this study were approved by the local Ethical Committee. The data were analysed on STATA 14.0 and GraphPad Prism 8.0. RESULTS: We observed the male dominant distribution in GC cohort and over 65% of GC were firstly diagnosed at advanced stages (III and IV). Anemia was detected in about 50% of GC patients. Hyponutrition was prevalent in newly diagnosed GC. We found the decreased tendency of anemia related indexes from HC to early stages (I and II) and advanced stages (III and IV) of GC patients. CONCLUSION: Anemia and hypoproteinemia occurred frequently among Vietnamese newly diagnosed GC. The nutrition therapy would benefit GC patients (Tab. 4, Fig. 4, Ref. 20).
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Anemia , Desnutrição , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Masculino , Feminino , Estudos Transversais , Pessoa de Meia-Idade , Vietnã/epidemiologia , Anemia/diagnóstico , Anemia/etiologia , Desnutrição/diagnóstico , Desnutrição/epidemiologia , Idoso , Adulto , Estadiamento de NeoplasiasRESUMO
Hepatocellular carcinoma (HCC) is the second lethal cancer. Short overall survival, low five-year survival rate, and unimproved treatment efficacy urge the need to improve HCC prognosis. Adiponectin is key protector against cancer and hepatic abnormalities. Hypoadiponectinemia occurs in and promotes carcinogenesis and hepatic diseases. Adiponectin reactivation by different methods showed impressive effect against cancer and hepatic diseases. Recently, AdipoRon, an adiponectin receptor agonist, can interact with both Adiponectin receptors. AdipoRon showed promising anti-cancer effect in some cancers, but no study on HCC yet. The in vitro effect of AdipoRon on HCC was investigated by cell viability, migration, invasion, colony formation and apoptosis assays. The signalling alteration was determined by RT-qPCR and Western blot. The effect of treatment was interpreted by comparison between treatments and control. The difference between two cell lines was relatively compared. Our results showed significant in vitro anti-cancer effect of AdipoRon via AMPK- and dose-dependent manner. Huh7 cells showed a lower level of AdipoR1/2 and a superior proliferation and aggressiveness, compared to Hep3B. In addition, Huh7 cells were more sensitive to AdipoRon treatment (lower IC50, less cell growth, migration, invasion and colonies upon AdipoRon treatment) than Hep3B cells. In conclusion, AdipoRon effectively inhibited HCC growth and invasiveness in vitro. The deficient expression of adiponectin receptors affects efficacy of AdipoRon and aggressiveness of HCC cells.
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Apoptose , Carcinoma Hepatocelular , Movimento Celular , Proliferação de Células , Neoplasias Hepáticas , Receptores de Adiponectina , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Receptores de Adiponectina/metabolismo , Receptores de Adiponectina/agonistas , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
The accurate recording of respiratory rate (RR) without contact is important for patient care. The current methods for RR measurement such as capnography, pneumography, and plethysmography require patient contact, are cumbersome, or not accurate for widespread clinical use. Video Plethysmography (VPPG) is a novel automated technology that measures RR using a facial video without contact. The objective of our study was to determine whether VPPG can feasibly and accurately measure RR without contact in surgical patients at a clinical setting. After research ethics approval, 216 patients undergoing ambulatory surgery consented to the study. Patients had a 1.5 min video of their faces taken via an iPad preoperatively, which was analyzed using VPPG to obtain RR information. The RR prediction by VPPG was compared to 60-s manual counting of breathing by research assistants. We found that VPPG predicted RR with 88.8% accuracy and a bias of 1.40 ± 1.96 breaths per minute. A significant and high correlation (0.87) was observed between VPPG-predicted and manually recorded RR. These results did not change with the ethnicity of patients. The success rate of the VPPG technology was 99.1%. Contactless RR monitoring of surgical patients at a hospital setting using VPPG is accurate and feasible, making this technology an attractive alternative to the current approaches to RR monitoring. Future developments should focus on improving reliability of the technology.
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Pletismografia , Taxa Respiratória , Humanos , Reprodutibilidade dos Testes , Monitorização Fisiológica/métodos , RespiraçãoRESUMO
The purpose of this study was to evaluate the feasibility and accuracy of remote Video Plethysmography (VPPG) for contactless measurements of blood pressure (BP) and heart rate (HR) in adult surgical patients in a hospital setting. An iPad Pro was used to record a 1.5-minute facial video of the participant's face and VPPG was used to extract vital signs measurements. A standard medical device (Welch Allyn) was used for comparison to measure BP and HR. Trial registration: NCT05165381. Two-hundred-sixteen participants consented and completed the contactless BP and HR monitoring (mean age 54.1 ± 16.8 years, 58% male). The consent rate was 75% and VPPG was 99% successful in capturing BP and HR. VPPG predicted SBP, DBP, and HR with a measurement bias ± SD, -8.18 ± 16.44 mmHg, - 6.65 ± 9.59 mmHg, 0.09 ± 6.47 beats/min respectively. Pearson's correlation for all measurements between VPPG and standard medical device was significant. Correlation for SBP was moderate (0.48), DBP was weak (0.29), and HR was strong (0.85). Most patients were satisfied with the non-contact technology with an average rating of 8.7/10 and would recommend it for clinical use. VPPG was highly accurate in measuring HR, and is currently not accurate in measuring BP in surgical patients. The VPPG BP algorithm showed limitations in capturing individual variations in blood pressure, highlighting the need for further improvements to render it clinically effective across all ranges. Contactless vital signs monitoring was well-received and earned a high satisfaction score.
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Assistência Perioperatória , Pletismografia , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Pressão Sanguínea/fisiologia , Frequência CardíacaRESUMO
Hydrophobins are remarkable proteins due to their ability to self-assemble into amphipathic coatings that reverse surface wettability. Here, the versatility of the Class I hydrophobins EASΔ15 and DewY in diverse nanosuspension and coating applications is demonstrated. The hydrophobins are shown to coat or emulsify a range of substrates including oil, hydrophobic drugs, and nanodiamonds and alter their solution and surface behavior. Surprisingly, while the coatings confer new properties, only a subset is found to be resistant to hot detergent treatment, a feature previously thought to be characteristic of the functional amyloid form of Class I hydrophobins. These results demonstrate that substrate surface properties can influence the molecular structures and physiochemical properties of hydrophobin and possibly other functional amyloids. Functional amyloid assembly with different substrates and conditions may be analogous to the propagation of different polymorphs of disease-associated amyloid fibrils with distinct structures, stability, and clinical phenotypes. Given that amyloid formation is not required for Class I hydrophobins to serve diverse applications, our findings open up new opportunities for their use in applications requiring a range of chemical and physical properties. In hydrophobin nanotechnological applications where high stability of assemblies is required, simultaneous structural and functional characterization should be carried out. Finally, while results in this study pertain to synthetic substrates, they raise the possibility that at least some members of the pseudo-Class I and Class III hydrophobins, reported to form assemblies with noncanonical properties, may be Class I hydrophobins adopting alternative structures in response to environmental cues.
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Amiloide , Proteínas Fúngicas , Proteínas Fúngicas/química , Molhabilidade , Interações Hidrofóbicas e Hidrofílicas , Propriedades de Superfície , Sequência de Aminoácidos , Amiloide/química , Proteínas AmiloidogênicasRESUMO
Gastric cancer (GC) is the remaining concern of cancer-associated health burden. Valuable predictive and prognostic indicators support the early diagnosis and improve outcome. Immune escape and inflammation are important cancer hallmarks. The prognostic and diagnostic value of platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) was reported in some cancers. But these cheap and convenient indexes are far from clinical use. Thus, investigation the alteration of those index on GC is needed to impose the use of those indexes in clinic. The study recruited seventy-seven hospitalized patients newly diagnosed with GC and 90 healthy individuals. The clinical and preclinical data of participants were collected from Hospital Information Management system. This study were approved by the Ethical Committee, Vietnam Military Medical University. The data were analyzed on STATA version 14.0 and GraphPad Prism 8.0. The alteration of immunological system was reported by significantly higher white blood cell count, neutrophils, platelets, PLR, and NLR as well as decreased lymphocytes on GC, compared to healthy individuals. Those indexes were elevated on advanced stage GC, compared to early stage GC. Our receiver operating characteristic curve analysis showed the significant specificity and sensitivity of PLR (cutoff 135.0) and NLR (cutoff 2.0) on GC diagnosis with respective area under receiver operating characteristic curve of 84.74% and 85.17%, Pâ <â .0001. Besides, our results reported the tendency of increased PLR and NLR and short time from clinical signs to being diagnosed. PLR and NLR have significant specificity and sensitivity in diagnosis and prognosis of GC.
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Plaquetas , Neoplasias Gástricas , Humanos , Neutrófilos , Prognóstico , Contagem de Plaquetas , Neoplasias Gástricas/diagnóstico , Linfócitos , Estudos RetrospectivosRESUMO
BACKGROUND: In clinical obstetrics, many guidelines recommended the use of Doppler fetal ductus venosus blood flow to monitor and to manage fetal growth restriction (FGR). The ductus venosus and the pulmonary venous flow pattern of fetuses are similar. Umbilical artery pH (UA pH) is essential in identifying adverse pregnancy outcomes, particularly in fetal growth restriction cases. Nevertheless, the literature indicates that the relationship between pulmonary vein pulsatility index (PVPI) and UA pH in FGR cases has not been well investigated. This study aimed to identify the alteration in PVPI in FGR cases and evaluate the correlation between PVPI and UA pH in FGR newborns. METHODS: This matched cohort study of singleton pregnancies from 28+ 0 to 40+ 0 weeks of gestation without congenital abnormalities included 135 cases of FGR (disease group) and 135 cases of normal growth (control group). The PVPI was measured at the proximal segment of the right or left pulmonary vein, approximately 5 mm from the left atrium wall. The umbilical artery pulsatility index (UAPI) was measured on the free umbilical cord. An elective cesarean section or labor induction are both options for ending the pregnancy, depending on the condition of the mother or fetus. Umbilical artery blood samples were collected within 5 min of delivery for UA pH measurement. SPSS version 20 and Medcalc version 20.1 were used for data analysis. RESULTS: FGR cases had a significantly higher mean fetal PVPI than the control group (1.16 ± 0.26 vs. 0.84 ± 0.16; p < 0.01), and PVPI and UAPI were positively correlated (r = 0.63; p < 0.001). PVPI and UA pH were negatively correlated in FGR patients, with r = -0.68; p < 0.001. The PVPI value on the 95th percentile had a prognostic value of UA pH < 7.20 with a sensitivity of 88.2%, specificity of 66.3%, positive predictive value of 46.9%, and negative predictive value of 94.3%. CONCLUSIONS: There was a statistically significant difference in PVPI values in FGR cases compared to the normal growth group, a positive correlation between PVPI and UAPI, and a negative correlation between PVPI and UA pH. PVPI might have a prognostic meaning in predicting UA pH at birth.
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Veias Pulmonares , Recém-Nascido , Gravidez , Humanos , Feminino , Veias Pulmonares/diagnóstico por imagem , Artérias Umbilicais/diagnóstico por imagem , Cesárea , Estudos de Coortes , Retardo do Crescimento Fetal/diagnóstico por imagem , População do Sudeste AsiáticoRESUMO
The main cannabinoid receptor CB1R first shows expression during early neurula stage in chicken (Gallus gallus) embryos, and at early tailbud stage in the frog (Xenopus laevis) embryos. This raises the question of whether CB1R regulates similar or distinct processes during the embryonic development of these two species. Here, we examined whether CB1R influences the migration and morphogenesis of neural crest cells and derivatives in both chicken and frog embryos. Early neurula stage chicken embryos were exposed to arachidonyl-2'-chloroethylamide (ACEA; a CB1R agonist), N-(Piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251; a CB1R inverse agonist) or Blebbistatin (nonmuscle Myosin II inhibitor) in ovo and examined during migration of neural crest cells and at condensing cranial ganglia stage. Early tailbud stage frog embryos were bathed in ACEA, AM251 or Blebbistatin, and analyzed at late tailbud stage for changes in craniofacial and eye morphogenesis, and in patterning and morphology of melanophores (neural crest-derived pigment cells). In chicken embryos exposed to ACEA and Myosin II inhibitor, cranial neural crest cells migrated erratically from the neural tube, and the right, but not the left, ophthalmic nerve of the trigeminal ganglia was affected in ACEA- and AM251-treated embryos. In frog embryos with inactivation or activation of CB1R, or inhibition of Myosin II, the craniofacial and eye regions were smaller and/or less developed, and the melanophores overlying the posterior midbrain were more dense, and stellate in morphology, than the same tissues and cells in control embryos. This data suggests that despite differences in the time of onset of expression, normal activity of CB1R is required for sequential steps in migration and morphogenesis of neural crest cells and derivatives in both chicken and frog embryos. In addition, CB1R may signal through Myosin II to regulate migration and morphogenesis of neural crest cells and derivatives in chicken and frog embryos.
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Galinhas , Crista Neural , Embrião de Galinha , Animais , Feminino , Agonismo Inverso de Drogas , Morfogênese , Desenvolvimento Embrionário , AnurosRESUMO
Macro-encapsulation systems for delivery of cellular therapeutics in diabetes treatment offer major advantages such as device retrievability and high cell packing density. However, microtissue aggregation and absence of vasculature have been implicated in the inadequate transfer of nutrients and oxygen to the transplanted cellular grafts. Herein, we develop a hydrogel-based macrodevice to encapsulate therapeutic microtissues positioned in homogeneous spatial distribution to mitigate their aggregation while concurrently supporting an organized intra-device network of vascular-inductive cells. Termed Waffle-inspired Interlocking Macro-encapsulation (WIM) device, this platform comprises two modules with complementary topography features that fit together in a lock-and-key configuration. The waffle-inspired grid-like micropattern of the "lock" component effectively entraps insulin-secreting microtissues in controlled locations while the interlocking design places them in a co-planar spatial arrangement with close proximity to vascular-inductive cells. The WIM device co-laden with INS-1E microtissues and human umbilical vascular endothelial cells (HUVECs) maintains desirable cellular viability in vitro with the encapsulated microtissues retaining their glucose-responsive insulin secretion while embedded HUVECs express pro-angiogenic markers. Furthermore, a subcutaneously implanted alginate-coated WIM device encapsulating primary rat islets achieves blood glucose control for 2 weeks in chemically induced diabetic mice. Overall, this macrodevice design lays foundation for a cell delivery platform, which has the potential to facilitate nutrients and oxygen transport to therapeutic grafts and thereby might lead to improved disease management outcome.
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FGFR3-TACC3 fusions have been identified in patients with multiple cancer types, and tumors with these alterations are potentially sensitive to selective FGFR inhibitors. However, there are no FGFR inhibitors approved by the U.S. Food and Drug Administration for the treatment of patients with NSCLC with FGFR alterations. Here, we report a case of a patient with FGFR3-TACC3 fusion squamous NSCLC who achieved a radiographic response and disease control for 11 months on initial treatment with erdafitinib and subsequently obtained an additional 8 months of disease control after erdafitinib retreatment after 5 months of intervening chemotherapy. Further investigation into FGFR inhibitor treatment specifically and targeted therapy retreatment for patients with NSCLC may increase our therapeutic options for these patients.
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We report the observation of nonlinear three-wave resonant interactions between two different branches of the dispersion relation of hydrodynamic waves, namely the gravity-capillary and sloshing modes. These atypical interactions are investigated within a torus of fluid for which the sloshing mode can be easily excited. A triadic resonance instability is then observed due to this three-wave two-branch interaction mechanism. An exponential growth of the instability and phase locking are evidenced. The efficiency of this interaction is found to be maximal when the gravity-capillary phase velocity matches the group velocity of the sloshing mode. For a stronger forcing, additional waves are generated by a cascade of three-wave interactions populating the wave spectrum. Such a three-wave two-branch interaction mechanism is probably not restricted to hydrodynamics and could be of interest in other systems involving several propagation modes.
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The RIP homotypic interaction motif (RHIM) is an essential protein motif in inflammatory signaling and certain cell death pathways. RHIM signaling occurs following the assembly of functional amyloids, and while the structural biology of such higher-order RHIM complexes has started to emerge, the conformations and dynamics of nonassembled RHIMs remain unknown. Here, using solution NMR spectroscopy, we report the characterization of the monomeric form of the RHIM in receptor-interacting protein kinase 3 (RIPK3), a fundamental protein in human immunity. Our results establish that the RHIM of RIPK3 is an intrinsically disordered protein motif, contrary to prediction, and that exchange dynamics between free monomers and amyloid-bound RIPK3 monomers involve a 20-residue stretch outside the RHIM that is not incorporated within the structured cores of the RIPK3 assemblies determined by cryo-EM or solid-state NMR. Thus, our findings expand on the structural characterization of RHIM-containing proteins, specifically highlighting conformational dynamics involved in assembly processes.
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Amiloide , Proteínas Amiloidogênicas , Humanos , Amiloide/química , Morte Celular , Proteínas Amiloidogênicas/metabolismo , Transdução de Sinais , Espectroscopia de Ressonância Magnética , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismoRESUMO
In the present study, distribution characteristics of ten typical phthalic acid esters (PAEs) were investigated in 90 air samples collected from the urban areas in Hanoi, Vietnam from May to August 2022. The total concentrations of PAEs in indoor and ambient air samples were in the range of 320-4770 ng/m3 and 35.9-133 ng/m3, respectively. Total concentrations of PAEs in indoor air were about one order of magnitude higher than those in ambient air. Among PAEs studied, di-(2-ethyl)hexyl phthalate (DEHP) was measured at the highest levels in all air samples, followed by di-n-octyl phthalate (DnOP) and di-n-butyl phthalate (DnBP). The PAEs concentrations in air samples collected from laboratories at nighttime were significantly higher than those during daytime (p < 0.05). Meanwhile, the distributions of PAEs in various micro-environments in the same house are no statistically significant difference. The median exposure doses of PAEs through inhalation for adults and children were 248 and 725 ng/kg-bw/d, respectively. These exposure levels were still lower than the respective reference doses (RfD) proposed by the US EPA for selected compounds such as diethyl phthalate (DEP), DnBP, and DEHP.
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Dietilexilftalato , Ácidos Ftálicos , Criança , Adulto , Humanos , Vietnã , Ésteres , Dibutilftalato , ChinaRESUMO
Chimeric antigen receptor (CAR) T cells and PD-1 antibodies (PD-1 Ab) are emergent immunotherapies with unprecedented efficacy. The presence of PD-1 on T cells contributes to hypofunction of CAR-T therapy and inhibition of PD-1 enhances anti-cancer effect of CAR-T cells. Therefore, the combination of CAR-T cells and PD-1 antibody is a promissing strategy for cancer treatment. This study aims to establish our in-house CAR-T cells and evaluate the safety of CAR-T cells in combination with PD-1 antibody in animals. The toxicity of CD19-CAR-T cells was examined using Swiss Webster mice. Four mouse groups were treated with control, CAR-T, PD-1 antibody or CAR-T + PD-1 antibody. Mice's overall status was monitored and recorded. At the end-point, hematological and biochemical indices were quantified, histopathology of liver and kidney was evaluated by pathologists. The relative abnormal ratio and absolute values were compared between groups. We generated our in-house CAR-T cells and used them for safety evaluation in mice. The increase in mouse weight was observed in all groups after treatment and the weight was comparable between groups. The hematological, biochemical and histopathological parameters were equivalent between groups, except for liver grain degeneration occurred in treatment groups. Thus, CAR-T cells, PD-1 Ab and their combination were safe in mice. We successfully produced our in-house CAR-T cells and the combination of our CAR-T cells and PD-1 antibody was safe in mice with comparable values of hematopoietic indices, liver and kidney functions. Longer follow-up might be necessary to evaluate their effect on the liver.
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Receptores de Antígenos de Linfócitos T , Receptores de Antígenos Quiméricos , Camundongos , Animais , Receptor de Morte Celular Programada 1 , Linhagem Celular Tumoral , Linfócitos T , Anticorpos , Imunoterapia Adotiva , Modelos TeóricosRESUMO
In recent years, the rapid development of deep learning approaches has paved the way to explore the underlying factors that explain the data. In particular, several methods have been proposed to learn to identify and disentangle these underlying explanatory factors in order to improve the learning process and model generalization. However, extracting this representation with little or no supervision remains a key challenge in machine learning. In this paper, we provide a theoretical outlook on recent advances in the field of unsupervised representation learning with a focus on auto-encoding-based approaches and on the most well-known supervised disentanglement metrics. We cover the current state-of-the-art methods for learning disentangled representation in an unsupervised manner while pointing out the connection between each method and its added value on disentanglement. Further, we discuss how to quantify disentanglement and present an in-depth analysis of associated metrics. We conclude by carrying out a comparative evaluation of these metrics according to three criteria, (i) modularity, (ii) compactness and (iii) informativeness. Finally, we show that only the Mutual Information Gap score (MIG) meets all three criteria.
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Background: Previous studies have identified TET1 as a potential key regulator of genes linked to asthma. TET1 has been shown to transcriptionally respond to house dust mite extract, an allergen known to directly cause allergic asthma development, and regulate the expression of genes involved in asthma. How TET1 regulates expression of these genes, however, is unknown. TET1 is a DNA demethylase; therefore, most prior research on TET1-based gene regulation has focused on how TET1 affects methylation. However, TET1 can also interact directly with transcription factors and histone modifiers to regulate gene expression. Understanding how TET1 regulates expression to contribute to allergic responses and asthma development thus requires a comprehensive approach. To this end, we measured mRNA expression, DNA methylation, chromatin accessibility and histone modifications in control and TET1 knockdown human bronchial epithelial cells treated or untreated with house dust mite extract. Results: Throughout our analyses, we detected strong similarities between the effects of TET1 knockdown alone and the effects of HDM treatment alone. One especially striking pattern was that both TET1 knockdown and HDM treatment generally led to decreased chromatin accessibility at largely the same genomic loci. Transcription factor enrichment analyses indicated that altered chromatin accessibility following the loss of TET1 may affect, or be affected by, CTCF and CEBP binding. TET1 loss also led to changes in DNA methylation, but these changes were generally in regions where accessibility was not changing. Conclusions: TET1 regulates gene expression through different mechanisms (DNA methylation and chromatin accessibility) in different parts of the genome in the airway epithelial cells, which mediates inflammatory responses to allergen. Collectively, our data suggest novel molecular mechanisms through which TET1 regulates critical pathways following allergen challenges and contributes to the development of asthma.
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Introduction: The COVID-19 pandemic has created significant stressors in Vietnamese adolescents' lives. Coping skills play important roles in helping adolescents contend with stress. This study aimed to evaluate adolescents' coping skills during the COVID-19 pandemic and examine how those skills are impacted by excessive internet use during this pandemic. Methods: The study used respondent-driven sampling and Google online survey forms to collect data. The study sample included 5,315 high school students aged 11- 17 years in Hanoi's rural and urban areas. The Kid Coping Scale was applied to examine adolescents' coping, and the coping score was compared among adolescents with different levels of internet use. Results: The average coping score measured by Kid Coping Scale was 20.40 (std = 2.13). About half of adolescents often "avoid the problem or the area where it happened" when experiencing a hard time. One-third of adolescents often stopped thinking about the problem they faced. More than one-fourth of respondents stayed online for at least 8 h per day. The online time for learning/other activities showed a reverse dose-response relationship with the coping score; the longer the internet use duration, the lower the coping score. Conclusion: The mean score of coping of Hanoi adolescents was moderate. Internet use has an adverse impact on their coping skills.
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COVID-19 , Adaptação Psicológica , Adolescente , COVID-19/epidemiologia , Humanos , Uso da Internet , Pandemias , Vietnã/epidemiologiaRESUMO
Liposomal encapsulation is a drug delivery strategy with many advantages, such as improved bioavailability, ability to carry large drug loads, as well as controllability and specificity towards various targeted diseased tissues. Currently, most preparation techniques require an additional extrusion or filtering step to obtain monodisperse liposomes with the size of less than 100 nm. In this study, a compact liposome extruder was designed at a cost of $4.00 and used to synthesize liposome suspensions with defined particle size and high homogeneity for Murrayafoline A (Mu-A) loading and release. The synthesized MuA-loaded liposomes displayed a biphasic drug release and remained stable under the storage condition of 4°C. They also significantly reduced the viability of HepG2 cells in the cancer spheroids by 25%. The low-cost, flexible liposome extruder would allow the researchers to study liposomes and their applications in a cost-effective manner.