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2.
Sensors (Basel) ; 24(15)2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39124114

RESUMO

Pedestrian trajectory prediction is crucial for developing collision avoidance algorithms in autonomous driving systems, aiming to predict the future movement of the detected pedestrians based on their past trajectories. The traditional methods for pedestrian trajectory prediction involve a sequence of tasks, including detection and tracking to gather the historical movement of the observed pedestrians. Consequently, the accuracy of trajectory prediction heavily relies on the accuracy of the detection and tracking models, making it susceptible to their performance. The prior research in trajectory prediction has mainly assessed the model performance using public datasets, which often overlook the errors originating from detection and tracking models. This oversight fails to capture the real-world scenario of inevitable detection and tracking inaccuracies. In this study, we investigate the cumulative effect of errors within integrated detection, tracking, and trajectory prediction pipelines. Through empirical analysis, we examine the errors introduced at each stage of the pipeline and assess their collective impact on the trajectory prediction accuracy. We evaluate these models across various custom datasets collected in Taiwan to provide a comprehensive assessment. Our analysis of the results derived from these integrated pipelines illuminates the significant influence of detection and tracking errors on downstream tasks, such as trajectory prediction and distance estimation.

3.
Pharmacology ; : 1-11, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38955142

RESUMO

INTRODUCTION: Kidney cancer ranks as the ninth most common cancer in men and the fourteenth in women globally, with renal cell carcinoma (RCC) being the most prevalent type. Despite advances in therapeutic strategies targeting angiogenesis and immune checkpoints, the absence of reliable markers for patient selection and limited duration of disease control underline the need for innovative approaches. CK1δ and CK1ε are highly conserved serine/threonine kinases involved in cell cycle regulation, apoptosis, and circadian rhythm. While CK1δ dysregulation is reportedly associated with breast and bladder cancer progression, their role in RCC remains elusive. This study aimed to investigate the feasibility of CK1δ/ε as new therapeutic targets for RCC patients. METHODS: The relationship between CK1δ/ε and RCC progression was evaluated by the analysis of microarray dataset and TCGA database. The anticancer activity of CK1δ/ε inhibitor was examined by MTT/SRB assay, and apoptotic cell death was analyzed by flow cytometry and Western blotting. RESULTS: Our data demonstrate that the gene expression of CSNK1D and CSNK1E is significantly higher in clear cell RCC (ccRCC) tissues compared to normal kidney samples, which is correlated with lower survival rates in ccRCC patients. SR3029, a selective inhibitor targeting CK1δ/ε, significantly suppresses the viability and proliferation of ccRCC cell lines regardless of the status of VHL deficiency. Importantly, the inhibitor promotes the population of subG1 cells and induces apoptosis, and ectopically expression of CK1δ partially rescued SR3029-induced apoptosis in ccRCC cells. CONCLUSION: These findings underscore the crucial role of CK1δ and CK1ε in ccRCC progression, suggesting CK1δ/ε inhibitors as new therapeutic options for ccRCC patients.

4.
J Public Health Manag Pract ; 30(4): 540-549, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38833668

RESUMO

CONTEXT: For many young children, early childcare and education (ECE) programs are the only source of nutritious meals and physical activity (PA); however, the COVID-19 pandemic led to program closures, restrictions, and changed practices. OBJECTIVE: To examine changes in nutrition and PA-related best practices in ECE settings in Illinois from 2019, just prior to the pandemic, as compared to 2022. We also examined how changes over time varied by program type (ie, centers vs homes), Child and Adult Care Food Program (CACFP) status, and/or Head Start/Early Head Start status. DESIGN: The study design is a repeated cross-sectional survey administered in December 2019 and October 2022. SETTING: State of Illinois. PARTICIPANTS: A total of 888 and 1162 ECE providers completed initial and follow-up surveys, respectively. INTERVENTION: NA. MAIN OUTCOME MEASURE: Provider report of meeting 14 nutrition and 9 PA-related best practices. RESULTS: Overall, 9 nutrition-related best practices were maintained and 5 declined over time. Centers, CACFP, and Head Start providers reported significant declines in meeting nutrition-related practices over time. A total of 8 PA-related best practices were maintained and 1 declined over time. Centers reported a significant decline in 5 of the PA-related best practices over time, and these declines were significantly different than in homes over time. Similarly, Head Start programs reported a decline in 4 PA-related best practices over time, and the change was significantly different from non-Head Start programs in 3 of the 4 practices. CONCLUSION: The findings of this study should be considered a new baseline for ECE nutrition and PA-related best practices in Illinois and should serve as a wake-up call for advocates nationwide with regard to the provision of nutrition and PA-related best practices in centers and by CACFP and Head Start providers postpandemic.


Assuntos
COVID-19 , Creches , Exercício Físico , SARS-CoV-2 , Humanos , Illinois/epidemiologia , COVID-19/prevenção & controle , COVID-19/epidemiologia , Estudos Transversais , Pré-Escolar , Creches/normas , Creches/estatística & dados numéricos , Pandemias/prevenção & controle , Feminino , Estado Nutricional , Masculino , Inquéritos e Questionários , Lactente
5.
Exp Gerontol ; 194: 112487, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38879092

RESUMO

BACKGROUND: Given the established association between sarcopenia and cognitive impairment was mainly in the older and oldest-old population or people with relatively limited education, this study extends the investigation to community-dwelling middle-to-old age adults in urban communities, emphasizing the need for preventive intervention for muscle health and healthy longevity. METHODS: Data of 712 participants from the Gan-Dau Healthy Longevity Plan were retrieved for analysis, and all participants were stratified by age (50-64, 65-74 and 75+ years old). Possible sarcopenia was defined by 2019 consensus report of the Asian Working Group for Sarcopenia (AWGS). This study used four neuropsychological tests for analysis, i.e., Mini-Mental Status Examination (MMSE), California Verbal Learning Test II (CVLT-SF), Digital Symbol Substitution Test (DSST) and Verbal fluency (VF) for global and domain-specific cognitive function. Multivariate generalized linear models (GLMs) were employed to investigate the associations between possible sarcopenia and cognitive function in each age-specific groups. RESULTS: The prevalence of possible sarcopenia increased with age, with 31.8 %, 37.7 %, and 55.6 % in participants aged 5064, 65-74 and, 75+ years, respectively. On the other hand, cognitive performance declined with age. In particular, among participants aged 75+ years with possible sarcopenia, their cognitive performance were poorer than robust counterparts, including MMSE (26.6 [3.4] vs. 27.4 [2.6]), CVTL-SF (total score: 21.5 [5.4] vs. 23.8 [5.5]; 30-second delayed recall: 6.0 [1.7] vs. 6.5 [1.6]), DSST (32.8 [14.3] vs. 41.3 [18.7]), and VF (12.8 [5.1] vs. 14.8 [4.9]). Multivariate generalized linear model indicated that possible sarcopenia was associated with lower MMSE (ß: -0.70, p = 0.014) and lower DSST (ß: -7.00, p = 0.010) in those aged 50-64 years. Moreover, possible sarcopenia was associated with lower CVLT-SF (total score ß:-1.90, p = 0.028), lower DSST (ß: -6.45, p < 0.001), and lower VF (ß: -1.64, p=0.026) in 75+ years group. CONCLUSIONS: An association exists between possible sarcopenia and cognitive impairment, encompassing global cognition, delayed memory, verbal fluency, and executive function, among community-dwelling adults of mid-to-old age. Future research is warranted to explore the temporal alterations in this association and the potential effects of interventions aimed at fostering healthy longevity.


Assuntos
Disfunção Cognitiva , Testes Neuropsicológicos , Sarcopenia , Humanos , Sarcopenia/epidemiologia , Idoso , Masculino , Feminino , Disfunção Cognitiva/epidemiologia , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Longevidade , Vida Independente , Prevalência , Cognição , República da Coreia/epidemiologia
7.
Artigo em Inglês | MEDLINE | ID: mdl-38862198

RESUMO

Automation of metabolite control in fermenters is fundamental to develop vaccine manufacturing processes more quickly and robustly. We created an end-to-end process analytical technology and quality by design-focused process by replacing manual control of metabolites during the development of fed-batch bioprocesses with a system that is highly adaptable and automation-enabled. Mid-infrared spectroscopy with an attenuated total reflectance probe in-line, and simple linear regression using the Beer-Lambert Law, were developed to quantitate key metabolites (glucose and glutamate) from spectral data that measured complex media during fermentation. This data was digitally connected to a process information management system, to enable continuous control of feed pumps with proportional-integral-derivative controllers that maintained nutrient levels throughout fed-batch stirred-tank fermenter processes. Continuous metabolite data from mid-infrared spectra of cultures in stirred-tank reactors enabled feedback loops and control of the feed pumps in pharmaceutical development laboratories. This improved process control of nutrient levels by 20-fold and the drug substance yield by an order of magnitude. Furthermore, the method is adaptable to other systems and enables soft sensing, such as the consumption rate of metabolites. The ability to develop quantitative metabolite templates quickly and simply for changing bioprocesses was instrumental for project acceleration and heightened process control and automation. ONE-SENTENCE SUMMARY: Intelligent digital control systems using continuous in-line metabolite data enabled end-to-end automation of fed-batch processes in stirred-tank reactors.


Assuntos
Reatores Biológicos , Fermentação , Vacinas , Glucose/metabolismo , Ácido Glutâmico/metabolismo , Espectrofotometria Infravermelho/métodos , Meios de Cultura/química , Técnicas de Cultura Celular por Lotes/métodos , Automação
8.
Sensors (Basel) ; 24(10)2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38793952

RESUMO

The convergence of edge computing systems with Field-Programmable Gate Array (FPGA) technology has shown considerable promise in enhancing real-time applications across various domains. This paper presents an innovative edge computing system design specifically tailored for pavement defect detection within the Advanced Driver-Assistance Systems (ADASs) domain. The system seamlessly integrates the AMD Xilinx AI platform into a customized circuit configuration, capitalizing on its capabilities. Utilizing cameras as input sensors to capture road scenes, the system employs a Deep Learning Processing Unit (DPU) to execute the YOLOv3 model, enabling the identification of three distinct types of pavement defects with high accuracy and efficiency. Following defect detection, the system efficiently transmits detailed information about the type and location of detected defects via the Controller Area Network (CAN) interface. This integration of FPGA-based edge computing not only enhances the speed and accuracy of defect detection, but also facilitates real-time communication between the vehicle's onboard controller and external systems. Moreover, the successful integration of the proposed system transforms ADAS into a sophisticated edge computing device, empowering the vehicle's onboard controller to make informed decisions in real time. These decisions are aimed at enhancing the overall driving experience by improving safety and performance metrics. The synergy between edge computing and FPGA technology not only advances ADAS capabilities, but also paves the way for future innovations in automotive safety and assistance systems.

9.
PeerJ Comput Sci ; 10: e2012, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38686001

RESUMO

Recently, large-scale artificial intelligence models with billions of parameters have achieved good results in experiments, but their practical deployment on edge computing platforms is often subject to many constraints because of their resource requirements. These models require powerful computing platforms with a high memory capacity to store and process the numerous parameters and activations, which makes it challenging to deploy these large-scale models directly. Therefore, model compression techniques are crucial role in making these models more practical and accessible. In this article, a progressive channel pruning strategy combining graph attention network and transformer, namely GAT TransPruning, is proposed, which uses the graph attention networks (GAT) and the attention of transformer mechanism to determine the channel-to-channel relationship in large networks. This approach ensures that the network maintains its critical functional connections and optimizes the trade-off between model size and performance. In this study, VGG-16, VGG-19, ResNet-18, ResNet-34, and ResNet-50 are used as large-scale network models with the CIFAR-10 and CIFAR-100 datasets for verification and quantitative analysis of the proposed progressive channel pruning strategy. The experimental results reveal that the accuracy rate only drops by 6.58% when the channel pruning rate is 89% for VGG-19/CIFAR-100. In addition, the lightweight model inference speed is 9.10 times faster than that of the original large model. In comparison with the traditional channel pruning schemes, the proposed progressive channel pruning strategy based on the GAT and Transformer cannot only cut out the insignificant weight channels and effectively reduce the model size, but also ensure that the performance drop rate of its lightweight model is still the smallest even under high pruning ratio.

10.
Surgery ; 176(1): 154-161, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38599982

RESUMO

BACKGROUND: Infections are commonly seen in wounds. The overall infection rate is 1.8% to 4.2%. Improper infection management can lead to serious conditions and may progress to life-threatening sepsis. Because there is a need for assistance in predicting wound infection before obvious clinical symptoms, the measurement of cytokines in wound tissue fluids has attracted our attention for determining the overall status of wound infection. Our intent was to assess the potential biomarkers in the diagnosis of wound infection. METHODS: We collected 146 tissue fluids (acute: 59, chronic: 61, and normal: 26) for analysis of biomarkers using a human cytokine array. Serum C-reactive protein was also measured from 104 patients. The sensitivity and specificity of significant wound cytokines and serum C-reactive protein for the diagnosis of wound infection were evaluated. RESULTS: Among biomarkers examined, serum C-reactive protein and tissue C-reactive protein were highly expressed in acute infection wounds, whereas monocyte chemoattractant protein-1 was significantly expressed in chronic infection wounds. Because the expression of wound biomarkers varied in different types of wounds, relationships among them were studied. A high correlation between tissue C-reactive protein and interleukin-8 (R2 = 0.7) and a moderate correlation between systemic and local C-reactive protein (R2 = 0.47) were observed. In addition, tissue monocyte chemoattractant protein-1 had better sensitivity (74%) and specificity (65%) in the diagnosis of wound infection. Moreover, combined serum C-reactive protein with monocyte chemoattractant protein-1 examination provided a higher area under the curve in the receiver operator characteristic curve (0.75). CONCLUSION: We found that tissue monocyte chemoattractant protein-1 is a superior diagnostic marker for assistance with the diagnosis of wound infection.


Assuntos
Biomarcadores , Proteína C-Reativa , Quimiocina CCL2 , Sensibilidade e Especificidade , Humanos , Quimiocina CCL2/análise , Quimiocina CCL2/metabolismo , Quimiocina CCL2/sangue , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Biomarcadores/metabolismo , Biomarcadores/análise , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Infecção dos Ferimentos/diagnóstico , Infecção dos Ferimentos/metabolismo , Idoso de 80 Anos ou mais , Interleucina-8/análise , Interleucina-8/metabolismo , Curva ROC , Líquidos Corporais/química , Líquidos Corporais/metabolismo
11.
J Oleo Sci ; 73(4): 583-591, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38556291

RESUMO

In this study, it is demonstrated that natural microalgae oils, which contain fatty acid components including docosahexaenoic acid (DHA), could be directly applied to fabricate vesicular structures in aqueous phase through a forced formation process. The microalgae oil vesicles had initial average diameters of 170- 230 nm with negative charges apparently caused by dissociation of the fatty acid components. The vesicles possessed excellent stability with lifetimes for at least 450 days. The formation of the vesicular structures with hydrophilic cores/regions was confirmed by the transmission electron microscopy (TEM) image and successful encapsulation of a hydrophilic material. For encapsulation of a hydrophobic material, lutein, the vesicle size was increased probably due to the insertion of lutein into the hydrophobic vesicular bilayer structures. The analysis of Fourier transform infrared (FTIR) spectroscopy suggested that the vesicular bilayer fluidity was decreased by encapsulating lutein. However, the lutein-encapsulating microalgae oil vesicles still possessed high stability and the vesicular structures could maintain intact even at an environmental temperature up to 60℃. Applicability of the microalgae oil vesicles as drug delivery carriers was also demonstrated by successful encapsulation of curcumin. However, when the loaded curcumin was increased to a certain amount, physical stability of the microalgae oil vesicles was significantly reduced. This is probably because the vesicular structures with only limited spaces for accommodating hydrophobic materials were strongly affected by encapsulating a large amount of curcumin. It is interesting to note that by adding egg L-α-phosphatidylcholine, the curcumin encapsulation-induced instability of the microalgae oil vesicles could be alleviated. The results indicated that vesicular structures could be fabricated from microalgae oils and the microalgae oil vesicles were capable of encapsulating hydrophilic or hydrophobic materials for drug delivery applications. The findings lay a background for further dosage form development of nutritional supplements encapsulated by natural microalgae oils.


Assuntos
Curcumina , Microalgas , Microalgas/química , Luteína , Óleos , Portadores de Fármacos/química , Ácidos Docosa-Hexaenoicos
12.
Clin Exp Dermatol ; 49(8): 887-892, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-38469681

RESUMO

Autosomal recessive congenital ichthyosis (ARCI) is a genetically heterogeneous disorder with aberrant skin scaling and increased transepidermal water loss (TEWL). Current treatments for ARCI are limited and suboptimal. We present the case of a 27-year-old man with ARCI resulting from a homozygous missense variant in TGM1. RNA-sequencing of lesional skin revealed aberrant Janus kinase-signal transducer and activator of transcription signalling, providing a rationale for innovative treatment with a Janus kinase inhibitor. We prescribed oral tofacitinib (11 mg daily) for 26 weeks. Rapid improvements in erythema and fissuring occurred within the first month. Sustained reductions in 5-D itch scale and Dermatology Life Quality Index scores were also observed. TEWL decreased for the first 10 weeks but increased thereafter. Tofacitinib downregulated inflammatory genes and pathways, while enhancing skin barrier markers. Moreover, transglutaminase 1 distribution was normalized although enzymatic activity remained deficient. This study suggests that oral tofacitinib may be a useful therapy to consider for patients with ARCI.


Assuntos
Piperidinas , Pirimidinas , Humanos , Masculino , Pirimidinas/uso terapêutico , Adulto , Piperidinas/uso terapêutico , Transglutaminases/genética , Mutação de Sentido Incorreto , Inibidores de Proteínas Quinases/uso terapêutico , Administração Oral , Pele/patologia
13.
Br J Dermatol ; 191(2): 252-260, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38477474

RESUMO

BACKGROUND: Dominant dystrophic epidermolysis bullosa (DDEB) is characterized by trauma-induced blisters and, in some individuals, intense pruritus. Precisely what causes itch in DDEB and optimal ways to reduce it have not been fully determined. OBJECTIVES: To characterize DDEB skin transcriptomes to identify therapeutic targets to reduce pruritus in patients. METHODS: Using bulk RNA sequencing, we evaluated affected and unaffected skin biopsy samples from six patients with DDEB (all with the very itchy pruriginosa subtype) and four healthy individuals. Single-cell transcriptomes of affected (n = 2) and unaffected (n = 1) DDEB skin and healthy skin (n = 2) were obtained. Dupilumab treatment was provided for three patients. RESULTS: The skin bulk transcriptome showed significant enrichment of T helper (Th)1/2 and Th17 pathways in affected DDEB skin compared with nonlesional DDEB skin and healthy skin. Single-cell transcriptomics showed an association of glycolytically active GATA3+ Th2 cells in affected DDEB skin. Treatment with dupilumab in three people with DDEB led to significantly reduced visual analogue scale (VAS) itch scores after 12 weeks (mean VAS 3.83) compared with pretreatment (mean VAS 7.83). Bulk RNAseq and quantitative polymerase chain reaction showed that healthy skin and dupilumab-treated epidermolysis bullosa (EB) pruriginosa skin have similar transcriptomic profiles and reduced Th1/Th2 and Th17 pathway enrichment. CONCLUSIONS: Single-cell RNAseq helps define an enhanced DDEB-associated Th2 profile and rationalizes drug repurposing of anti-Th2 drugs in treating DDEB pruritus.


Dominant dystrophic epidermolysis bullosa (DDEB) is a rare inherited skin disease that causes fragile skin that blisters easily, often triggered by minor injuries. These blisters are accompanied by intense itching, which can be distressing. The underlying cause of DDEB lies in genetic mutations in a gene called COL7A1. This gene encodes 'type VII collagen', a protein crucial for attaching the outer skin layer (epidermis) to the layer beneath (dermis). Although the genetic basis of DDEB is understood, the causes of itch are not known. As well as this, effective treatments for DDEB are lacking, which has driven scientists to explore innovative approaches like repurposing existing drugs. Drug repurposing involves using medications that have already been approved for other health conditions. One such drug is dupilumab, which is used for severe atopic dermatitis (eczema). Dupilumab targets immune cells called Th2 cells, which play a role in inflammation and allergies. While dupilumab has shown promise in relieving DDEB itching, the way it works in this condition is unclear. This study, carried out by a group of researchers in Taiwan, looked at gene expression in DDEB-affected and unaffected skin, and compared it to gene expression in healthy skin samples. We found heightened activity in Th2 immune cells and abnormal gene signals related to itching, similar to atopic dermatitis. These findings support using dupilumab and other anti-inflammatory drugs to alleviate itching in DDEB. Clinical trials will be crucial to evaluate the effectiveness of these drugs for managing DDEB symptoms. This research opens doors for enhanced treatment options and improving the quality of life of people living with DDEB.


Assuntos
Anticorpos Monoclonais Humanizados , Epidermólise Bolhosa Distrófica , Fator de Transcrição GATA3 , Prurido , Pele , Células Th2 , Humanos , Epidermólise Bolhosa Distrófica/complicações , Epidermólise Bolhosa Distrófica/imunologia , Epidermólise Bolhosa Distrófica/genética , Epidermólise Bolhosa Distrófica/patologia , Prurido/etiologia , Prurido/imunologia , Prurido/tratamento farmacológico , Prurido/patologia , Células Th2/imunologia , Anticorpos Monoclonais Humanizados/farmacologia , Masculino , Fator de Transcrição GATA3/metabolismo , Fator de Transcrição GATA3/genética , Feminino , Pele/imunologia , Pele/patologia , Adulto , Transcriptoma , Estudos de Casos e Controles , Pessoa de Meia-Idade , Análise de Célula Única
14.
MycoKeys ; 101: 275-312, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38333551

RESUMO

Pestalotiopsissensu lato, commonly referred to as pestalotiopsis-like fungi, exhibit a broad distribution and are frequently found as endophytes, saprobes and pathogens across various plant hosts. The taxa within pestalotiopsis-like fungi are classified into three genera viz. Pestalotiopsis, Pseudopestalotiopsis and Neopestalotiopsis, based on the conidial colour of their median cells and multi-locus molecular phylogenies. In the course of a biodiversity investigation focusing on pestalotiopsis-like fungi, a total of 12 fungal strains were identified. These strains were found to be associated with stromata of Beauveria, Ophiocordyceps and Tolypocladium in various regions of Taiwan from 2018 to 2021. These strains were evaluated morphologically and multi-locus phylogenetic analyses of the ITS (internal transcribed spacer), tef1-α (translation elongation factor 1-α) and tub2 (beta-tubulin) gene regions were conducted for genotyping. The results revealed seven well-classified taxa and one tentative clade in Pestalotiopsis and Neopestalotiopsis. One novel species, Pestalotiopsismanyueyuanani and four new records, N.camelliae-oleiferae, N.haikouensis, P.chamaeropis and P.hispanica, were reported for the first time in Taiwan. In addition, P.formosana and an unclassified strain of Neopestalotiopsis were identified, based on similarities of phylogeny and morphology. However, the data obtained in the present study suggest that the currently recommended loci for species delimitation of pestalotiopsis-like fungi do not deliver reliable or adequate resolution of tree topologies. The in-vitro mycelial growth rates of selected strains from these taxa had an optimum temperature of 25 °C, but growth ceased at 5 °C and 35 °C, while all the strains grew faster under alkaline than acidic or neutral pH conditions. This study provides the first assessment of pestalotiopsis-like fungi, associated with entomopathogenic taxa.

16.
J Biomed Sci ; 31(1): 12, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38254097

RESUMO

BACKGROUND: Pathologic scars, including keloids and hypertrophic scars, represent a common form of exaggerated cutaneous scarring that is difficult to prevent or treat effectively. Additionally, the pathobiology of pathologic scars remains poorly understood. We aim at investigating the impact of TEM1 (also known as endosialin or CD248), which is a glycosylated type I transmembrane protein, on development of pathologic scars. METHODS: To investigate the expression of TEM1, we utilized immunofluorescence staining, Western blotting, and single-cell RNA-sequencing (scRNA-seq) techniques. We conducted in vitro cell culture experiments and an in vivo stretch-induced scar mouse model to study the involvement of TEM1 in TGF-ß-mediated responses in pathologic scars. RESULTS: The levels of the protein TEM1 are elevated in both hypertrophic scars and keloids in comparison to normal skin. A re-analysis of scRNA-seq datasets reveals that a major profibrotic subpopulation of keloid and hypertrophic scar fibroblasts greatly expresses TEM1, with expression increasing during fibroblast activation. TEM1 promotes activation, proliferation, and ECM production in human dermal fibroblasts by enhancing TGF-ß1 signaling through binding with and stabilizing TGF-ß receptors. Global deletion of Tem1 markedly reduces the amount of ECM synthesis and inflammation in a scar in a mouse model of stretch-induced pathologic scarring. The intralesional administration of ontuxizumab, a humanized IgG monoclonal antibody targeting TEM1, significantly decreased both the size and collagen density of keloids. CONCLUSIONS: Our data indicate that TEM1 plays a role in pathologic scarring, with its synergistic effect on the TGF-ß signaling contributing to dermal fibroblast activation. Targeting TEM1 may represent a novel therapeutic approach in reducing the morbidity of pathologic scars.


Assuntos
Cicatriz Hipertrófica , Queloide , Fator de Crescimento Transformador beta , Animais , Humanos , Camundongos , Antígenos CD , Antígenos de Neoplasias , Cicatriz Hipertrófica/metabolismo , Fibroblastos , Queloide/metabolismo , Pele
17.
Viruses ; 16(1)2024 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-38257842

RESUMO

This study aimed to explore the current evidence on preventing blood-borne virus infections among people who inject drugs (PWID). We conducted a comprehensive search across three databases (PubMed, Embase, Cochrane Library) for relevant articles published in English between 2014 and 2023. We followed the Preferred Reporting Items for Systematic Reviews and Meta Analysis (PRISMA) guidelines, assessed the quality of the paper using the revised Cochrane Risk of Bias Tool (ROB 2), and conducted a meta-analysis using RevMan 5.3. Completing the harm reduction program (HRP) participation and receiving all three vaccine doses resulted in a 28% reduction in the risk of HBV infection (OR: 0.72, 95% CI: 0.37-1.42). Various interventions increased the willingness of PWIDs to undergo HCV treatment (OR: 5.91, 95% CI: 2.46-14.24) and promoted treatment adherence (OR: 15.04, 95% CI: 2.80-80.61). Taking PrEP, participating in HRP, and modifying risky behaviors were associated with a 33% reduction in the risk of HIV infection (OR: 0.67, 95% CI: 0.61-0.74). Conducting referrals, providing counseling, and implementing antiretroviral therapy resulted in a 44% reduction in the risk of viral transmission (OR: 0.56, 95% CI: 0.47-0.66). Co-infection may potentially compromise effectiveness, so it is important to consider drug resistance.


Assuntos
Coinfecção , Usuários de Drogas , Infecções por HIV , Hepatite Viral Humana , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Coinfecção/prevenção & controle , Bases de Dados Factuais
18.
J Invest Dermatol ; 144(7): 1491-1504.e10, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38218364

RESUMO

Acne keloidalis is a primary scarring alopecia characterized by longstanding inflammation in the scalp causing keloid-like scar formation and hair loss. Histologically, acne keloidalis is characterized by mixed leukocytic infiltrates in the acute stage followed by a granulomatous reaction and extensive fibrosis in the later stages. To further explore its pathogenesis, bulk RNA sequencing, single-cell RNA sequencing, and spatial transcriptomics were applied to occipital scalp biopsy specimens of lesional and adjacent no-lesional skin in patients with clinically active disease. Unbiased clustering revealed 19 distinct cell populations, including 2 notable populations: POSTN+ fibroblasts with enriched extracellular matrix signatures and SPP1+ myeloid cells with an M2 macrophage phenotype. Cell communication analyses indicated that fibroblasts and myeloid cells communicated by SPP1 signaling networks in lesional skin. A reverse transcriptomics in silico approach identified corticosteroids as possessing the capability to reverse the gene expression signatures of SPP1+ myeloid cells and POSTN+ fibroblasts. Intralesional corticosteroid injection greatly reduced SPP1 and POSTN gene expression as well as acne keloidalis disease activity. Spatial transcriptomics and immunofluorescence staining verified microanatomic specificity of SPP1+ myeloid cells and POSTN+ fibroblasts with disease activity. In summary, the communication between POSTN+ fibroblasts and SPP1+ myeloid cells by SPP1 axis may contribute to the pathogenesis of acne keloidalis.


Assuntos
Acne Queloide , Fibroblastos , Macrófagos , Humanos , Fibroblastos/metabolismo , Fibroblastos/patologia , Macrófagos/metabolismo , Macrófagos/patologia , Acne Queloide/patologia , Acne Queloide/metabolismo , Osteopontina/metabolismo , Osteopontina/genética , Fibrose , Masculino , Moléculas de Adesão Celular/metabolismo , Moléculas de Adesão Celular/genética , Feminino , Adulto , Cicatriz/patologia , Couro Cabeludo/patologia , Comunicação Celular , Biópsia , Queloide/patologia , Queloide/metabolismo
20.
Membranes (Basel) ; 13(12)2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38132903

RESUMO

The CO2 absorption by Monoethanolamine (MEA) solutions as chemical absorption was conducted in the membrane gas absorption module with inserting 3D mini-channel turbulence promoters of the present work. A mathematical modeling of CO2 absorption flux was analyzed by using the chemical absorption theory based on mass-transfer resistances in series. The membrane absorption module with embedding 3D mini-channel turbulence promoters in the current study indicated that the CO2 absorption rate improvement is achieved due to the diminishing concentration polarization effect nearby the membrane surfaces. A simplified regression equation of the average Sherwood number was correlated to express the enhanced mass-transfer coefficient of the CO2 absorption. The experimental results and theoretical predictions showed that the absorption flux improvement was significantly improved with implementing 3D mini-channel turbulence promoters. The experimental results of CO2 absorption fluxes were performed in good agreement with the theoretical predictions in aqueous MEA solutions. A further absorption flux enhancement up to 30.56% was accomplished as compared to the results in the previous work, which the module was inserted the promoter without mini channels. The influences of the MEA absorbent flow rates and inlet CO2 concentrations on the absorption flux and absorption flux improvement are also illustrated under both concurrent- and countercurrent-flow operations.

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