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1.
Int J Mol Sci ; 25(13)2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-39000454

RESUMO

Chronic obstructive pulmonary disease (COPD) plays a significant role in global morbidity and mortality rates, typified by progressive airflow restriction and lingering respiratory symptoms. Recent explorations in molecular biology have illuminated the complex mechanisms underpinning COPD pathogenesis, providing critical insights into disease progression, exacerbations, and potential therapeutic interventions. This review delivers a thorough examination of the latest progress in molecular research related to COPD, involving fundamental molecular pathways, biomarkers, therapeutic targets, and cutting-edge technologies. Key areas of focus include the roles of inflammation, oxidative stress, and protease-antiprotease imbalances, alongside genetic and epigenetic factors contributing to COPD susceptibility and heterogeneity. Additionally, advancements in omics technologies-such as genomics, transcriptomics, proteomics, and metabolomics-offer new avenues for comprehensive molecular profiling, aiding in the discovery of novel biomarkers and therapeutic targets. Comprehending the molecular foundation of COPD carries substantial potential for the creation of tailored treatment strategies and the enhancement of patient outcomes. By integrating molecular insights into clinical practice, there is a promising pathway towards personalized medicine approaches that can improve the diagnosis, treatment, and overall management of COPD, ultimately reducing its global burden.


Assuntos
Biomarcadores , Doença Pulmonar Obstrutiva Crônica , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/genética , Humanos , Biomarcadores/metabolismo , Estresse Oxidativo , Proteômica/métodos , Genômica/métodos , Metabolômica/métodos , Epigênese Genética
2.
J Cell Mol Med ; 28(12): e18489, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38899522

RESUMO

This study explores the impact of senescence on autocrine C-C motif chemokine ligand 5 (CCL5) in human endothelial progenitor cell (EPCs), addressing the poorly understood decline in number and function of EPCs during ageing. We examined the effects of replication-induced senescence on CCL5/CCL5 receptor (CCR5) signalling and angiogenic activity of EPCs in vitro and in vivo. We also explored microRNAs controlling CCL5 secretion in senescent EPCs, its impact on EPC angiogenic activity, and validated our findings in humans. CCL5 secretion and CCR5 levels in senescent EPCs were reduced, leading to attenuated angiogenic activity. CCL5 enhanced EPC proliferation via the CCR5/AKT/P70S6K axis and increased vascular endothelial growth factor (VEGF) secretion. Up-regulation of miR-409 in senescent EPCs resulted in decreased CCL5 secretion, inhibiting the angiogenic activity, though these negative effects were counteracted by the addition of CCL5 and VEGF. In a mouse hind limb ischemia model, CCL5 improved the angiogenic activity of senescent EPCs. Analysis involving 62 healthy donors revealed a negative association between CCL5 levels, age and Framingham Risk Score. These findings propose CCL5 as a potential biomarker for detection of EPC senescence and cardiovascular risk assessment, suggesting its therapeutic potential for age-related cardiovascular disorders.


Assuntos
Senescência Celular , Quimiocina CCL5 , Células Progenitoras Endoteliais , MicroRNAs , Neovascularização Fisiológica , Animais , Humanos , Masculino , Camundongos , Angiogênese , Proliferação de Células , Quimiocina CCL5/metabolismo , Quimiocina CCL5/genética , Regulação para Baixo/genética , Células Progenitoras Endoteliais/metabolismo , Células Progenitoras Endoteliais/citologia , Isquemia/metabolismo , Isquemia/patologia , Isquemia/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Neovascularização Fisiológica/genética , Receptores CCR5/metabolismo , Receptores CCR5/genética , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética
3.
Pediatr Int ; 66(1): e15777, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38863264

RESUMO

BACKGROUND: We aimed to compare the clinical features and severity of the Omicron and Delta variant infections among children hospitalized for coronavirus disease 2019 (COVID-19). METHODS: Children 12 years old or less hospitalized for COVID-19 across five hospitals between January 1, 2021 and March 31, 2022 were identified using the state's pediatric COVID-19 registry. Delta and Omicron-infected patients without previous COVID-19 infection, COVID-19 vaccination, or co-infections were propensity-score matched 1:1 to control for differences in baseline characteristics. Clinical manifestations, treatments, and outcomes were analyzed. Disease severity was assessed using an adapted WHO ordinal scale. RESULTS: Of the initial 1367 patients, 668 had Delta infection and 699 had Omicron infection. Propensity-score matching produced 558 matched pairs. Patients with Omicron infection were more likely to present with croup (the odds ratio, OR, was 10.87, with a 95% confidence interval, CI, ranging from 2.54 to 46.59), lower respiratory tract infection (OR 2.32, 95% CI, 1.48-3.64) and seizures (OR 8.39, 95% CI, 5.04-13.99) compared with those with Delta infection. Omicron was associated with increased odds of moderate/severe disease (OR 6.14, 95% CI, 4.72-7.99) and a greater need for intravenous fluid therapy (OR 6.00, 95% CI, 4.29-8.39), corticosteroids (OR 3.08, 95% CI, 1.66-5.72), empirical antibiotics (OR 1.70, 95% CI, 1.10-2.64), and low-flow nasal oxygen therapy (OR 3.68, 95% CI, 2.17-6.22) in comparison with Delta. CONCLUSION: Children hospitalized with Omicron infection demonstrated a distinct clinical profile compared to those with Delta infection, with increased likelihood of moderate/severe disease and higher utilization of health-care resources.


Assuntos
COVID-19 , SARS-CoV-2 , Índice de Gravidade de Doença , Humanos , COVID-19/epidemiologia , Criança , Masculino , Feminino , Pré-Escolar , Lactente , Hospitalização/estatística & dados numéricos , Pontuação de Propensão , Estudos Retrospectivos , Sistema de Registros
4.
Heliyon ; 10(9): e30493, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38726193

RESUMO

Aims: This study aimed to evaluate the prevalence of cognitive impairment among patients with acute heart failure (AHF), its prognosis, and the effects of cardiac rehabilitation (CR) on these patients' outcomes. Methods: Overall, 247 consecutive AHF patients (median age, 60 years; males, 78.5 %) were evaluated from March 2015 to May 2021. Patients received an AHF disease management program coordinated by an HF specialist nurse and underwent a Luria-Nebraska Neuropsychological battery-screening test (LNNB-S) assessment during admission. Cognitive impairment was defined as an LNNB-S score ≥10. Patients who underwent at least one session of phase II CR and continued with the home-based exercise program were considered to have received CR. The primary endpoint was composite all-cause mortality or readmission after a 3.30-year follow-up (interquartile range, 1.69-5.09 years). Results: Cognitive impairment occurred in 53.0 % and was associated with significantly higher composite endpoint, all-cause mortality, and readmission rates (p=<0.001, 0.001, and 0.015, respectively). In the total cohort, 40.9 % of patients experienced the composite endpoint. Multivariate analysis showed that the peak VO2 was a significant predictor of the composite endpoint. After adjustment, CR significantly decreased the event rate of the composite endpoint and the all-cause mortality in patients with cognitive impairment (log-rank p = 0.024 and 0.009, respectively). However, CR did not have a significant benefit on the composite endpoint and the all-cause mortality in patients without cognitive impairment (log-rank p = 0.682 and 0.701, respectively). Conclusion: Cognitive impairment is common in AHF patients and can lead to poor outcomes. CR is a standard treatment to improve prognosis.

5.
Biomedicines ; 12(4)2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38672169

RESUMO

Chronic obstructive pulmonary disease (COPD) is a prevalent and debilitating respiratory disorder characterized by persistent airflow limitation and chronic inflammation. In recent years, the role of mitochondrial dysfunction in COPD pathogenesis has emerged as a focal point of investigation. This review endeavors to unravel the molecular nexus between mitochondrial dysfunction and COPD, delving into the intricate interplay of oxidative stress, bioenergetic impairment, mitochondrial genetics, and downstream cellular consequences. Oxidative stress, a consequence of mitochondrial dysfunction, is explored as a driving force behind inflammation, exacerbating the intricate cascade of events leading to COPD progression. Bioenergetic impairment sheds light on the systemic consequences of mitochondrial dysfunction, impacting cellular functions and contributing to the overall energy imbalance observed in COPD patients. This review navigates through the genetic landscape, elucidating the role of mitochondrial DNA mutations, variations, and haplogroups in COPD susceptibility and severity. Cellular consequences, including apoptosis, autophagy, and cellular senescence, are examined, providing insights into the intricate mechanisms by which mitochondrial dysfunction influences COPD pathology. Therapeutic implications, spanning antioxidant strategies, mitochondria-targeted compounds, and lifestyle modifications, are discussed in the context of translational research. Important future directions include identifying novel biomarkers, advancing mitochondria-targeted therapies, and embracing patient-centric approaches to redefine COPD management. This abstract provides a comprehensive overview of our review, offering a roadmap for understanding and addressing the molecular nexus between mitochondrial dysfunction and COPD, with potential implications for precision medicine and improved patient outcomes.

6.
PLoS One ; 19(4): e0302234, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38625889

RESUMO

It is challenging to detect arbitrary-shape text accurately and effectively in natural scenes. While many methods have been implemented for arbitrary-shape text detection, most cannot achieve real-time detection or meet practical needs. In this work, we propose a YOLOv6-based detector that can effectively implement arbitrary-shape text detection and achieve real-time detection. We include two additional branches in the neck part of the YOLOv6 network to adapt the network to text detection, and the output side uses the pixel aggregation (PA) algorithm to decouple the PA output to use it as the detection head of the model. Experiments on benchmark Total-Text, CTW1500, ICDAR2015, and MSRA-TD500 showed that the proposed method outperformed competing methods in terms of detection accuracy and running time. Specifically, our method achieved an F-measure of 84.1% at 291.8 FPS for 640 × 640 Total-Text images and an F-measure of 81.5% at 199.6 FPS for 896 × 896 ICDAR2015 incidental text images.


Assuntos
Algoritmos , Redes Neurais de Computação
7.
Network ; : 1-29, 2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38433470

RESUMO

As the number of patients increases, physicians are dealing with more and more cases of degenerative spine pathologies on a daily basis. To reduce the workload of healthcare professionals, we propose a modified Swin-UNet network model. Firstly, the Swin Transformer Blocks are improved using a residual post-normalization and scaling cosine attention mechanism, which makes the training process of the model more stable and improves the accuracy. Secondly, we use the log-space continuous position biasing method instead of the bicubic interpolation position biasing method. This method solves the problem of performance loss caused by the large difference between the resolution of the pretraining image and the resolution of the spine image. Finally, we introduce a segmentation smooth module (SSM) at the decoder stage. The SSM effectively reduces redundancy, and enhances the segmentation edge processing to improve the model's segmentation accuracy. To validate the proposed method, we conducted experiments on a real dataset provided by hospitals. The average segmentation accuracy is no less than 95%. The experimental results demonstrate the superiority of the proposed method over the original model and other models of the same type in segmenting the spinous processes of the vertebrae and the posterior arch of the spine.

8.
Kaohsiung J Med Sci ; 40(5): 467-476, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38523603

RESUMO

Combining epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with an anti- vascular endothelial growth factor (VEGF) agent, bevacizumab or ramucirumab, is indicated for advanced lung adenocarcinoma harboring EGFR mutation. This study aimed to show the real-world data of combination therapy and compare the effectiveness between bevacizumab and ramucirumab in combination with an EGFR-TKI. This retrospective study enrolled 47 patients diagnosed of stage IV lung adenocarcinoma with exon 19 deletion or L858R point mutation, receiving a first-line EGFR-TKI with anti-VEGF agent, including 34 (72%) and 13 (28%) patients receiving bevacizumab and ramucirumab, respectively. The response rate was similar in both groups (p = 0.38). Patients receiving bevacizumab had similar progression free survival (PFS) as those receiving ramucirumab (median PFS: 21.9 vs. 24.2 months, p = 0.4871); similar finding was noted in overall survival (OS) (median OS: 33.5 months vs. not reached, p = 0.4618). Patients receiving ramucirumab experienced a significantly high-grade hypertension compared to those receiving bevacizumab (p = 0.0351). Multivariable Cox regression analysis found independent risk factors for worse PFS included poorer ECOG performance status, multiple (≥3) metastatic sites, brain metastasis, and pleural metastasis/effusion, while the type of anti-VEGF agent was not a risk factor. Pericardial metastasis/effusion was the only one independent risk factor for worse OS. In summary, ramucirumab may have similar effectiveness as bevacizumab in combination with an EGFR-TKI as first line therapy for advanced lung adenocarcinoma harboring susceptible EGFR mutation. Further large-scale registry-based cohort studies may be needed to validate our findings.


Assuntos
Anticorpos Monoclonais Humanizados , Bevacizumab , Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Neoplasias Pulmonares , Mutação , Inibidores de Proteínas Quinases , Ramucirumab , Humanos , Masculino , Feminino , Receptores ErbB/genética , Receptores ErbB/antagonistas & inibidores , Bevacizumab/uso terapêutico , Bevacizumab/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Pessoa de Meia-Idade , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resultado do Tratamento , Adulto , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Estadiamento de Neoplasias , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia
9.
Medicina (Kaunas) ; 60(2)2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38399533

RESUMO

Background and Objectives: Recent studies suggest that hydrogen gas possesses anti-inflammatory, antioxidant, and anti-apoptotic properties. This study aimed to explore the therapeutic potential of hydrogen gas and assess its safety and tolerability in individuals with chronic obstructive pulmonary disease (COPD). Materials and Methods: Enrolled COPD patients received standard treatments along with additional hydrogen inhalation for 30 min in the morning, afternoon, and evening over a 30-day period. The assessment included changes in the COPD Assessment Test (CAT), the modified Medical Research Council (mMRC) Dyspnea Scale, lung function, sleep quality, inflammation markers, and oxidative stress markers before and after hydrogen inhalation. Results: Six patients participated in this study. Patients 2, 3, 4, 5, and 6 demonstrated improvements in CAT scores following hydrogen gas intervention, with patients 2, 4, 5, and 6 also showing improvements in mMRC scores. Statistically, this study revealed significant improvements in CAT [15.5 (10.5-19.75) vs. 8.5 (3-13.5); p = 0.043] and mMRC scores [2.5 (1-4) vs. 2 (0-3.25); p = 0.046] before and after intervention, respectively. However, no significant differences were observed in lung function, DLCO, sleep quality, and 6 MWT before and after hydrogen therapy. CBC examination showed a significant difference in platelet count before and after treatment [247 (209.75-298.75) vs. 260 (232.75-314.5); p = 0.043], respectively, while other blood tests, inflammation markers, and oxidative stress markers did not exhibit significant differences before and after hydrogen therapy. All patients experienced no obvious side-effects. Conclusions: Adjuvant therapy with hydrogen gas demonstrated symptom improvements in specific COPD patients, and no significant adverse effects were observed in any of the patients. Hydrogen gas may also exert a modulatory effect on platelet count.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Humanos , Volume Expiratório Forçado , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Assistência Odontológica , Inflamação , Terapia Combinada , Índice de Gravidade de Doença
10.
Front Psychol ; 15: 1290122, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38348260

RESUMO

This study delves into the intricate relationships among job involvement (JI), perceived organizational support (POS), job insecurity (JIS), and organizational commitment (OC), with a particular focus on the mediating role of JIS within the context of the Malaysian private sector. The research delves into the antecedents of job insecurity and organizational commitment, offering insights to enhance commitment. Our study involved 440 employees in the Malaysian private sector, utilizing self-report questionnaires administered online. Notably, our findings underscore the significance of employment flexibility, job positions, and tenure in shaping JIS. Furthermore, we identify significant relationships among the variables: POS negatively predicts JIS, while JI, JIS, and POS collectively predict OC, with JIS partially mediating the POS-OC relationship. These empirically-grounded insights offer actionable guidance for organizations, empowering human resources practitioners to craft effective talent retention strategies and allocate resources strategically. In doing so, organizations can enhance employee productivity and bolster organizational commitment, ultimately contributing to sustained success in a dynamic work environment. These findings hold valuable implications for human resources practitioners, guiding the development of talent retention strategies and resource allocation to enhance employee productivity.

12.
Sensors (Basel) ; 23(23)2023 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-38067952

RESUMO

Due to frequent traffic accidents around the world, people often take out car insurance to mitigate their losses and receive compensation in a traffic accident. However, in the existing car insurance claims process, there are problems such as insurance fraud, inability to effectively track and transmit insurance data, cumbersome insurance procedures, and high insurance data storage costs. Since the immutability and traceability features of blockchain technology can prevent data manipulation and trace past data, we have used the Elliptic Curve Digital Signature Algorithm (ECDSA) to sign and encrypt car insurance data, ensuring both data integrity and security. We propose a blockchain and IPFS-based anticounterfeiting and traceable car insurance claims system to improve the above problems. We incorporate the Interplanetary File System (IPFS) to reduce the cost of storing insurance data. This study also attempts to propose an arbitration mechanism in the event of a car insurance dispute.

13.
Pediatr Int ; 65(1): e15690, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38037505

RESUMO

BACKGROUND: We describe the epidemiology, clinical characteristics, and outcomes of multisystem inflammatory syndrome in children (MIS-C) among children from Negeri Sembilan, Malaysia. METHODS: A retrospective, multicentre, observational study was performed among children ≤15 years old who were hospitalized for MIS-C between January 18, 2021 and June 30, 2023. The incidence of MIS-C was estimated using reported SARS-CoV-2 cases and census population data. Descriptive analyses were used to summarize the clinical presentation and outcomes. RESULTS: The study included 53 patients with a median age of 5.7 years (IQR 1.8-8.7 years); 75.5% were males. The overall incidence of MIS-C was approximately 5.9 cases per 1,000,000 person-months. Pediatric intensive care unit (PICU) admission was required for 22 (41.5%) patients. No mortalities were recorded. Children aged 6-12 years were more likely to present with cardiac dysfunction/shock (odds ratio [OR] 5.43, 95% confidence interval [CI] 1.67-17.66), whereas children below 6 years were more likely to present with a Kawasaki disease phenotype (OR 5.50, 95% CI 1.33-22.75). Twenty patients (37.7%) presented with involvement of at least four organ systems, but four patients (7.5%) demonstrated single-organ system involvement. CONCLUSION: An age-based variation in the clinical presentation of MIS-C was demonstrated. Our findings suggest MIS-C could manifest in a spectrum, including single-organ involvement. Despite the high requirement for PICU admission, the prognosis of MIS-C was favorable, with no recorded mortalities.


Assuntos
COVID-19 , Síndrome de Resposta Inflamatória Sistêmica , Criança , Masculino , Humanos , Lactente , Pré-Escolar , Adolescente , Feminino , Estudos Retrospectivos , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/epidemiologia , Síndrome de Resposta Inflamatória Sistêmica/terapia , COVID-19/epidemiologia , COVID-19/terapia , SARS-CoV-2
14.
Diagnostics (Basel) ; 13(24)2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38132239

RESUMO

Currently, over 200,000 new cases of leprosy are reported annually worldwide. Although leprosy was thought to have been eradicated in Taiwan, a few new cases still occur annually. Protean clinical manifestations of leprosy and immunological reactions result in delayed diagnoses. In addition, drug-resistant leprosy is emerging and poses treatment challenges. In this retrospective study, we collected and analyzed the clinicopathological features, leprosy type, treatment response, and relapse rate of patients with leprosy in our hospital between January 2009 and November 2022. We found that 54% of patients were Indonesian, and borderline lepromatous leprosy was predominant (39%); moreover, histoid leprosy and the Lucio phenomenon were also reported. Polymerase chain reaction analysis identified four positive cases, including a dapsone-resistant (4%) case. Our findings indicated good control of leprosy and a lower rate of dapsone resistance than that reported by the World Health Organization (4% vs. 13%) from 2009 to 2015. We found that the patient profile in terms of the treatment duration, recurrence rate, systemic symptoms, and neurological symptoms did not differ between before and during the pandemic. We report the recent advances in leprosy diagnosis, drug-resistant gene mutations, post-exposure prophylaxis, vaccination, and the effect of coronavirus disease 2019 on leprosy to facilitate updated leprosy diagnosis and management.

15.
Arterioscler Thromb Vasc Biol ; 43(10): 1935-1951, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37589139

RESUMO

BACKGROUND: We examined the role of Panxs (pannexins) in human endothelial progenitor cell (EPC) senescence. METHODS: Young and replication-induced senescent endothelial colony-forming cells (ECFCs) derived from human circulating EPCs were used to examine cellular activities and senescence-associated indicators after transfection of short interference RNA specific to Panx1 or lentivirus-mediated Panx1 overexpression. Hind limb ischemia mice were used as in vivo angiogenesis model. Protein and phospho-kinase arrays were used to determine underlying mechanisms. RESULTS: Panx1 was the predominant Panx isoform in human ECFCs and upregulated in both replication-induced senescent ECFCs and circulating EPCs from aged mice and humans. Cellular activities of the young ECFCs were enhanced by Panx1 downregulation but attenuated by its upregulation. In addition, reduction of Panx1 in the senescent ECFCs could rejuvenate cellular activities with reduced senescence-associated indicators, including senescence-associated ß-galactosidase activity, p16INK4a (cyclin-dependent kinase inhibitor 2A), p21 (cyclin-dependent kinase inhibitor 1), acetyl-p53 (tumor protein P53), and phospho-histone H2A.X (histone family member X). In mouse ischemic hind limbs injected senescent ECFCs, blood perfusion ratio, salvaged limb outcome, and capillary density were all improved by Panx1 knockdown. IGF-1 (insulin-like growth factor 1) was significantly increased in the supernatant from senescent ECFCs after Panx1 knockdown. The enhanced activities and paracrine effects of Panx1 knockdown senescent ECFCs were completely inhibited by anti-IGF-1 antibodies. FAK (focal adhesion kinase), ERK (extracellular signal-regulated kinase), and STAT3 (signal transducer and activator of transcription 3) were activated in senescent ECFCs with Panx1 knockdown, in which the intracellular calcium level was reduced, and the activation was inhibited by supplemented calcium. The increased IGF-1 in Panx1-knockdown ECFCs was abrogated, respectively, by inhibitors of FAK (PF562271), ERK (U0126), and STAT3 (NSC74859) and supplemented calcium. CONCLUSIONS: Panx1 expression is upregulated in human ECFCs/EPCs with replication-induced senescence and during aging. Angiogenic potential of senescent ECFCs is improved by Panx1 reduction through increased IGF-1 production via activation of the FAK-ERK axis following calcium influx reduction. Our findings provide new strategies to evaluate EPC activities and rejuvenate senescent EPCs for therapeutic angiogenesis.


Assuntos
Fator de Crescimento Insulin-Like I , Proteína Supressora de Tumor p53 , Animais , Humanos , Camundongos , Cálcio/metabolismo , Células Cultivadas , Senescência Celular , Conexinas/genética , Conexinas/metabolismo , Quinases Ciclina-Dependentes/metabolismo , Quinases Ciclina-Dependentes/farmacologia , Isquemia/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteína Supressora de Tumor p53/genética
16.
Sensors (Basel) ; 23(13)2023 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-37447987

RESUMO

Distributed Denial of Service (DDoS) attacks pose a significant threat to internet and cloud security. Our study utilizes a Poisson distribution model to efficiently detect DDoS attacks with a computational complexity of O(n). Unlike Machine Learning (ML)-based algorithms, our method only needs to set up one or more Poisson models for legitimate traffic based on the granularity of the time periods during preprocessing, thus eliminating the need for training time. We validate this approach with four virtual machines on the CDX 3.0 platform, each simulating different aspects of DDoS attacks for offensive, monitoring, and defense evaluation purposes. The study further analyzes seven diverse DDoS attack methods. When compared with existing methods, our approach demonstrates superior performance, highlighting its potential effectiveness in real-world DDoS attack detection.


Assuntos
Algoritmos , Internet , Aprendizado de Máquina
17.
Commun Biol ; 6(1): 610, 2023 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-37280327

RESUMO

Chronic heavy alcohol use is associated with lethal arrhythmias. Whether common East Asian-specific aldehyde dehydrogenase deficiency (ALDH2*2) contributes to arrhythmogenesis caused by low level alcohol use remains unclear. Here we show 59 habitual alcohol users carrying ALDH2 rs671 have longer QT interval (corrected) and higher ventricular tachyarrhythmia events compared with 137 ALDH2 wild-type (Wt) habitual alcohol users and 57 alcohol non-users. Notably, we observe QT prolongation and a higher risk of premature ventricular contractions among human ALDH2 variants showing habitual light-to-moderate alcohol consumption. We recapitulate a human electrophysiological QT prolongation phenotype using a mouse ALDH2*2 knock-in (KI) model treated with 4% ethanol, which shows markedly reduced total amount of connexin43 albeit increased lateralization accompanied by markedly downregulated sarcolemmal Nav1.5, Kv1.4 and Kv4.2 expressions compared to EtOH-treated Wt mice. Whole-cell patch-clamps reveal a more pronounced action potential prolongation in EtOH-treated ALDH2*2 KI mice. By programmed electrical stimulation, rotors are only provokable in EtOH-treated ALDH2*2 KI mice along with higher number and duration of ventricular arrhythmia episodes. The present research helps formulate safe alcohol drinking guideline for ALDH2 deficient population and develop novel protective agents for these subjects.


Assuntos
Aldeído-Desidrogenase Mitocondrial , Etanol , Síndrome do QT Longo , Animais , Humanos , Camundongos , Aldeído-Desidrogenase Mitocondrial/genética , Arritmias Cardíacas/genética , População do Leste Asiático , Etanol/toxicidade , Síndrome do QT Longo/induzido quimicamente , Camundongos Transgênicos
18.
BMC Infect Dis ; 23(1): 398, 2023 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-37308825

RESUMO

BACKGROUND: Children account for a significant proportion of COVID-19 hospitalizations, but data on the predictors of disease severity in children are limited. We aimed to identify risk factors associated with moderate/severe COVID-19 and develop a nomogram for predicting children with moderate/severe COVID-19. METHODS: We identified children ≤ 12 years old hospitalized for COVID-19 across five hospitals in Negeri Sembilan, Malaysia, from 1 January 2021 to 31 December 2021 from the state's pediatric COVID-19 case registration system. The primary outcome was the development of moderate/severe COVID-19 during hospitalization. Multivariate logistic regression was performed to identify independent risk factors for moderate/severe COVID-19. A nomogram was constructed to predict moderate/severe disease. The model performance was evaluated using the area under the curve (AUC), sensitivity, specificity, and accuracy. RESULTS: A total of 1,717 patients were included. After excluding the asymptomatic cases, 1,234 patients (1,023 mild cases and 211 moderate/severe cases) were used to develop the prediction model. Nine independent risk factors were identified, including the presence of at least one comorbidity, shortness of breath, vomiting, diarrhea, rash, seizures, temperature on arrival, chest recessions, and abnormal breath sounds. The nomogram's sensitivity, specificity, accuracy, and AUC for predicting moderate/severe COVID-19 were 58·1%, 80·5%, 76·8%, and 0·86 (95% CI, 0·79 - 0·92) respectively. CONCLUSION: Our nomogram, which incorporated readily available clinical parameters, would be useful to facilitate individualized clinical decisions.


Assuntos
COVID-19 , Modelos Estatísticos , Humanos , Criança , Prognóstico , Fatores de Risco , Gravidade do Paciente
19.
Foods ; 12(11)2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-37297453

RESUMO

Precision farming provides one of the most important solutions for managing agricultural production to advance global food security. Extending professionals' competencies to promote precision farming practices can increase the adoption rate, ultimately impacting food security. Many studies have addressed barriers to the adoption of precision farming technologies from the farmers' perspective. However, few are available data on the perspectives of extension professionals. Agricultural extension professionals play an important role in innovative agricultural technology adoption. Thus, this study applied four constructs from the unified theory of acceptance and use of technology (UTAUT) model to investigate behavioral intentions to promote precision farming among extension professionals from two extension systems. In total, 102 (N = 102) agricultural extension professionals were surveyed. The results indicated that performance expectancy and social influence were individually significant predictors of extension professional behavioral intentions to promote precision farming technologies. There were no significant differences between the professionals of two extension systems. Gender, age, and years of service did not affect extension professionals' intention to promote precision agriculture technologies. The data suggested the need for training programs to develop advanced competencies to promote agricultural innovation. This study contributes to the future professional development programs for extension professionals on communicating innovations to address food security and sustainability issues.

20.
Pediatr Int ; 65(1): e15565, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37368506

RESUMO

BACKGROUND: This study aimed to describe the clinical characteristics and severity of young infants hospitalized with COVID-19 and study the relationship between breastfeeding and maternal COVID-19 vaccination on the severity of COVID-19. METHODS: A retrospective, observational study was performed among infants aged 6 months and below hospitalized for COVID-19 in a tertiary state hospital in Malaysia between February 1 and April 30, 2022. The primary outcome was "serious disease," defined as pneumonia requiring respiratory support or dehydration with warning signs. Multivariate logistic regression was used to determine independent predictors for serious disease. RESULTS: A total of 102 infants were included in the study; 53.9% were males with a median age of 11 weeks (interquartile range: 5-20 weeks). Sixteen patients (15.7%) had pre-existing comorbidities, including preterm birth. Fever was the most common presenting symptom (82.4%), followed by cough (53.9%), and rhinorrhea (31.4%). Forty-one infants (40.2%) presented with serious disease, warranting either respiratory support or intravenous fluid therapy for dehydration. Recent maternal COVID-19 vaccination was associated with a reduced risk of serious disease on univariate analysis but was not significant after multivariate adjustment (adjusted odds ratio [aOR] 0.39; 95% CI: 0.14-1.11; p = 0.08). Exclusive breastfeeding was protective against serious COVID-19 in young infants, independent of other confounding factors (aOR 0.21, 95% CI: 0.06-0.71; p = 0.01). CONCLUSION: COVID-19 is a serious disease with non-specific clinical manifestations in young infants. Exclusive breastfeeding could play an important protective role.


Assuntos
Aleitamento Materno , COVID-19 , Desidratação , Pneumonia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Aleitamento Materno/efeitos adversos , COVID-19/diagnóstico , COVID-19/epidemiologia , Vacinas contra COVID-19/administração & dosagem , Desidratação/complicações , Desidratação/epidemiologia , Gravidade do Paciente , Estudos Retrospectivos , Fatores de Risco , Pneumonia/complicações , Pneumonia/epidemiologia , Respiração Artificial , Hospitalização
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