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1.
Heart Views ; 25(1): 21-29, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774552

RESUMO

Cardiac rehabilitation (CR) is recommended for all patients with stable angina (SA) as an effective treatment. Hemoglobin (Hgb) levels predict exercise performance and may affect symptom threshold in SA patients. A multidisciplinary CR intervention was individually tailored for a 72-year-old patient with a diagnosis of SA, low Hgb (<10 g/dL), and typical chest pain at light-to-moderate exercise (<5 metabolic equivalent task), who was stratified as at high risk for cardiac events during exercise. Two symptom-limited exercise tests were performed before and after 36 sessions of supervised exercise training producing near-optimal accumulated total volume load and chronic training load. In this case report, we show that an individually tailored CR intervention in a patient with SA and low Hgb is feasible, effective, and safe at reducing the burden of symptoms while increasing peak exercise capacity, health-related quality of life, and physical activity engagement.

2.
Int J Biol Macromol ; 270(Pt 2): 132252, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38729503

RESUMO

In this study, we developed a novel nanocomposite by synthesizing zinc (ZnNPs), copper (CuNPs), and silver (AgNPs) nanoparticles using olive leaf extract and incorporating them into a chitosan polymer. This approach combines the biocompatibility of chitosan with the antimicrobial and anticancer properties of metal nanoparticles, enhanced by the phytochemical richness of olive leaf extract. The significance of our research lies in its potential to offer a biodegradable and stable alternative to conventional antibiotics and cancer treatments, particularly in combating multidrug-resistant bacteria and various cancer types. Comprehensive characterization through Fourier Transform Infrared Spectroscopy (FTIR), X-Ray Diffraction (XRD), Thermogravimetric Analysis (TGA), Scanning Electron Microscopy (SEM), Energy Dispersive X-ray (EDX), and Transmission Electron Microscopy (TEM) confirmed the successful synthesis of the nanocomposites, with an average size of ~22.6 nm. Phytochemical analysis highlighted the antioxidant-rich composition of both the olive leaf extract and the nanoparticles themselves. Functionally, the synthesized nanoparticles exhibited potent antimicrobial activity against multidrug-resistant bacterial strains, outperforming traditional antibiotics by inhibiting key resistance genes (ermC, tetX3-q, blaZ, and Ery-msrA). In anticancer assessments, the nanoparticles showed selective cytotoxicity towards cancer cells in a concentration-dependent manner, with CuNPs and AgNPs showing particularly strong anticancer effects, while demonstrating minimal toxicity towards normal cells. ZnNPs were noted for their low cytotoxicity, highlighting the safety profile of these nanoparticles. Further, the nanoparticles induced apoptosis in cancer cells, as evidenced by the modulation of oncogenes (P21, P53, and BCL2), suggesting their therapeutic potential. The findings of our study underscore the versatile applications of these biogenic nanoparticles in developing safer and more effective antimicrobial and anticancer therapies.

3.
Can J Cardiol ; 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38679319

RESUMO

This is a case of a 76-year-old male with an initial presentation consistent with idiopathic pericarditis. He presented repeatedly with recurrent pericardial effusions and intrapericardial thrombi of unknown etiology. Surgical evacuation of the thrombi was performed twice, and the second surgery demonstrated a cardiac tumour. Cardiac MRI and pathology were consistent with angiosarcoma. In cases of recurrent pericardial effusions and thrombi, we recommend a high index of suspicion for cardiac tumours. Further, we recommend early consideration of cardiac MRI or PET and early referral to imaging specialists and cardiac surgeons with experience in cardiac tumours.

4.
Cells ; 13(8)2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38667314

RESUMO

The clinical management of bladder cancer continues to present significant challenges. Bacillus Calmette-Guérin (BCG) immunotherapy remains the gold standard of treatment for non-muscle invasive bladder cancer (NMIBC), but many patients develop recurrence and progression to muscle-invasive disease (MIBC), which is resistant to BCG. This review focuses on the immune mechanisms mobilized by BCG in bladder cancer tumor microenvironments (TME), mechanisms of BCG resistance, the dual role of the BCG-triggered NFkB/TNFα/PGE2 axis in the regulation of anti-tumor and tumor-promoting aspects of inflammation, and emerging strategies to modulate their balance. A better understanding of BCG resistance will help develop new treatments and predictive biomarkers, paving the way for improved clinical outcomes in bladder cancer patients.


Assuntos
Vacina BCG , Imunoterapia , Microambiente Tumoral , Neoplasias da Bexiga Urinária , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/terapia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Humanos , Microambiente Tumoral/imunologia , Vacina BCG/uso terapêutico , Vacina BCG/imunologia , Imunoterapia/métodos , Animais
5.
Iran J Med Sci ; 49(3): 156-166, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38584650

RESUMO

Background: Human papillomavirus (HPV)-related multi phenotypic sinonasal carcinoma (HMSC) is a recently described tumor subtype with an unknown prognosis, often misdiagnosed with other sinonasal carcinomas, and associated with high-risk HPV (HR-HPV). The present study aimed to evaluate the expression of vascular endothelial growth factor (VEGF), Bcl-2-associated X protein (BAX), epidermal growth factor receptors (EGFR), ProExTMC, and human telomerase reverse transcriptase (hTERT) and assess their association with survival and clinicopathological characteristics. Methods: Between 2017 and 2022, 40 HMSC patients underwent surgical resection at the School of Medicine, Zagazig University Hospitals (Zagazig, Egypt). Tissue samples were examined for the presence of HR-HPV; absence of myeloblastosis (MYB), MYB proto-oncogene like 1 (MYBL1), and nuclear factor I/B (NFIB) fusions and the presence of myoepithelial proteins (calponin, S100, SMA), squamous differentiation markers (p63, p40, calponin), VEGF, BAX, ProExTMC, and hTERT by immunohistochemistry. All patients were followed up for about 54 months until death or the last known survival data. Data were analyzed using the Chi square test and Kaplan-Meier method. Results: The expression of VEGF, hTERT, and ProExTMC was significantly associated with age, advanced tumor stages, lymph node metastasis, tumor size, mortality, relapse, poor disease-free survival (DFS), and overall survival (OS) (P<0.001). BAX expression was significantly associated with tumor size, age, poor DFS, and relapse (P=0.01, P<0.001, P=0.035, and P=0.002, respectively). Conclusion: HMSC is strongly associated with HR-HPV. The expression of VEGF, EGFR, BAX, hTERT, and ProExTMC is associated with aggressive malignant behavior, poor survival, and poor prognosis, making them novel prognostic biomarkers for targeted therapeutics in HMSC.


Assuntos
Carcinoma , Infecções por Papillomavirus , Neoplasias dos Seios Paranasais , Humanos , Fator A de Crescimento do Endotélio Vascular , Proteína X Associada a bcl-2 , Papillomavirus Humano , Prognóstico , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Papillomaviridae , Recidiva Local de Neoplasia/complicações , Carcinoma/diagnóstico , Carcinoma/patologia , Neoplasias dos Seios Paranasais/diagnóstico , Neoplasias dos Seios Paranasais/patologia , Receptores ErbB , Recidiva , Biomarcadores
6.
Womens Health (Lond) ; 20: 17455057241240920, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38576125

RESUMO

BACKGROUND: Urinary tract infections and reproductive tract infections pose significant health risks, particularly among women living in challenging conditions. Unhygienic menstrual practices can exacerbate these risks, impacting physical and psychological well-being. OBJECTIVES: This study assessed the association between unhygienic menstrual care and self-reported urinary tract infection/reproductive tract infection symptoms among refugee women. In addition, it explored the association between these symptoms and mental health, specifically depressive symptoms. DESIGN: This study adopted a cross-sectional observational design. METHODS: This study was conducted between January and March 2023, involving 387 reproductive-age refugee women. Data collected included sociodemographic information and urinary tract infection/reproductive tract infection symptoms. In addition, we used the Menstrual Practice Needs Scale to evaluate menstrual hygiene practices and the Patient Health Questionnaire-9 for depressive symptoms. Statistical analysis was performed using Python version 3.9.12. RESULTS: Of 387 refugee women, 92.25% reported having urinary or reproductive tract infection symptoms in the previous 3 months. Factors like older age (odds ratio = 1.764, 95% confidence interval = 1.083-2.873, p-value = 0.023), lower family income (odds ratio = 0.327, 95% confidence interval = 0.138-0.775, p-value = 0.011), lower educational level (odds ratio = 0.222, 95% confidence interval = 0.068-0.718, p-value = 0.012), and being married (odds ratio = 0.328, 95% confidence interval = 0.188-0.574, p-value < 0.001) were significantly associated with urinary or reproductive tract infection risk. Difficulties obtaining menstrual products and thus reusing them increased the odds of urinary or reproductive tract infection diagnosis (odds ratio = 2.452, 95% confidence interval = 1.497-4.015, p-value < 0.001). Women with urinary or reproductive tract infection symptoms exhibited higher Patient Health Questionnaire-9 scores than those without (12.14 ± 5.87 vs 9.99 ± 5.86, p-value < 0.001, respectively). CONCLUSION: This study highlights a high prevalence of urinary or reproductive tract infection symptoms among refugee women residing in camps in Jordan, which was associated with poor menstrual hygiene practices and depressive symptoms. To reduce the urinary tract infection/reproductive tract infection burden in marginalized communities, public health initiatives should enhance healthcare accessibility, provide reproductive education, and promote holistic well-being practices for refugee women.


Assuntos
Infecções do Sistema Genital , Infecções Urinárias , Humanos , Feminino , Menstruação/psicologia , Higiene , Infecções do Sistema Genital/diagnóstico , Infecções do Sistema Genital/epidemiologia , Estudos Transversais , Jordânia/epidemiologia , Campos de Refugiados , Infecções Urinárias/epidemiologia
7.
JCEM Case Rep ; 2(3): luae042, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38495395

RESUMO

Radioactive iodine therapy and posttreatment scanning are essential components of differentiated thyroid carcinoma treatment and detection of metastatic disease. False-positive results can be seen on an I-131 scan and are important for clinicians to be aware of. Here, we present a case of a 33-year-old female with follicular thyroid carcinoma who was noted to have an area of moderate uptake in the chest on a whole-body scan following remnant ablation with 30 mCi of I-131 (1.11GBq) concerning for a metastatic hilar lymph node. This was determined to be a mediastinal bronchogenic cyst on surgical pathology. It has been previously proposed that the expression of sodium iodide symporters in some bronchogenic cysts could be the mechanism by which iodine uptake is seen within them. We were able to demonstrate positive immunohistochemical staining for both sodium iodide symporter and the associated paired box gene 8 transcription factor in the cyst sample, which supports the proposed theory.

8.
ACS Omega ; 9(11): 13086-13099, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38524478

RESUMO

Addressing industrial wastewater treatment challenges and removing hazardous organic pollutants, such as carcinogenic methyl orange (MO) and azo dyes, is a pressing concern. This study explores the use of the Zea mays envelope, an agricultural waste product, to produce Z. mays activated carbon (ZMAC) through the chemical activation of maize envelopes with phosphoric acid. Various analytical techniques, including FTIR, XRD, TGA, DSC, and SEM, characterize ZMAC. Results show that ZMAC exhibits an impressive monolayer adsorption capacity of 66.2 mg/g for MO. The Langmuir isotherm model fits the experimental data well, indicating monolayer coverage of the MO on the ZMAC surface. The pH-sensitive adsorption process demonstrates an optimal removal efficiency at pH 4. ZMAC follows the pseudo-second-order kinetic model, and diffusion rate constant analysis identifies three consecutive stages in the adsorption process. Moreover, the uptake of MO ions by ZMAC is identified as an exothermic and spontaneous process. Reusability tests demonstrate efficient regeneration of ZMAC up to five times with 1 mL of 2 M HNO3 in each cycle, without sorbent mass loss. Thermodynamic analysis shows an increase in the uptake capacity from 66.2 to 73.2 mg/g with temperature elevation. This study offers practical solutions for industrial wastewater treatment challenges, providing an environmentally sustainable and effective approach to mitigate the risks associated with hazardous organic pollutants.

9.
Plant Physiol Biochem ; 207: 108421, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38335887

RESUMO

Plant fungal diseases impose a formidable challenge for global agricultural productivity, a meticulous examination of host-pathogen interactions. In this intricate study, an exhaustive investigation was conducted on infected tomatoes obtained from Egyptian fields, leading to the precise molecular identification of the fungal isolate as Alternaria alternata (OP881811), and the isolate showed high identity with Chinese isolates (ON973896 and ON790502). Subsequently, fourteen diverse tomato cultivars; Cv Ferment, Cv 103, Cv Damber, Cv 186, Cv 4094, Cv Angham, Cv N 17, Cv Gesma, Cv 010, Cv branch, cv 2020, Cv 023, Cv Gana and Cv 380 were meticulously assessed to discern their susceptibility levels upon inoculation with Alternaria alternata. Thorough scrutiny of disease symptom manifestation and the extent of tomato leaf damage ensued, enabling a comprehensive evaluation of cultivar responses. Results unveiled a spectrum of plant susceptibility, with three cultivars exhibiting heightened vulnerability (Cv Ferment, Cv 103 and Cv Damber), five cultivars displaying moderate susceptibility (Cv 186, Cv 4094, Cv Angham, Cv N 17 and Cv Gesma), and six cultivars demonstrating remarkable resilience to the pathogen (Cv 010, Cv branch, cv, 2020; Cv 023, Cv Gana and Cv 380). In order to gain a thorough understanding of the underlying physiological patterns indicative of plant resistance against A. alternata, an in-depth exploration of polyphenols, flavonoids, and antioxidant enzymes ensued. These key indicators were closely examined, offering valuable insights into the interplay between plant physiology and pathogen response. Robust correlations emerged, with higher contents of these compounds correlating with heightened susceptibility, while lower levels were indicative of enhanced plant tolerance. In tandem with the physiological assessment, a thorough investigation of four pivotal defensive genes (PR5, PPO, PR3, and POX) was undertaken, employing cutting-edge Real-Time PCR technology. Gene expression profiles displayed intriguing variations across the evaluated tomato cultivars, ultimately facilitating the classification of cultivars into distinct groups based on their levels of resistance, moderate susceptibility, or heightened sensitivity. By unravelling the intricate dynamics of plant susceptibility, physiological responses, and patterns of gene expression, this comprehensive study paves the way for targeted strategies to combat plant fungal diseases. The findings contribute valuable insights into host-pathogen interactions and empower agricultural stakeholders with the knowledge required to fortify crop resilience and safeguard global food security.


Assuntos
Micoses , Solanum lycopersicum , Solanum lycopersicum/genética , Estresse Fisiológico , Alternaria
10.
Iran J Med Sci ; 49(2): 88-100, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38356485

RESUMO

Background: Epstein-Barr virus (EBV) is detected in 40% of patients with Hodgkin lymphoma (HL). During latency, EBV induces epigenetic alterations to the host genome and decreases the expression of pro-apoptotic proteins. The present study aimed to evaluate the expression levels of mRNA molecules and the end product of proteins for the JAK/STAT and NF-κB pathways, and their association with clinicopathological and prognostic parameters in patients with EBV-positive and -negative classical Hodgkin lymphoma (CHL). Methods: A prospective cohort study was conducted from 2017 to 2022 at the Faculty of Medicine, Zagazig University Hospital (Zagazig, Egypt). Biopsy samples of 64 patients with CHL were divided into EBV-positive and EBV-negative groups. The expression levels of mRNA molecules (JAK2, STAT1, IRF-1, PD-L1, IFN-γ, NF-κB, Bcl-xL, COX-2) and the end product of proteins (PD-L1, Bcl-xL, COX-2) were determined and compared with clinicopathological and prognostic parameters. Data were analyzed using the Chi square test and Kaplan-Meier estimate. Results: EBV-positive CHL patients were significantly associated with positive expression of mRNAs molecules (P<0.001) and the end product of proteins (P<0.001) for the JAK/STAT and NF-κB pathways, B-symptoms (P=0.022), extra-nodal involvement (P=0.017), and advanced stage of CHL (P=0.018). These patients were more susceptible to cancer progression, higher incidence of relapse (P=0.008), poor disease-free survival rate (P=0.013), poor overall survival rate (P=0.028), and higher mortality rate (P=0.015). Conclusion: Through the activation of JAK/STAT and NF-κB signaling pathways, EBV-positive CHL is associated with poor clinicopathological parameters, higher incidence of disease progression, relapse, and poor overall survival. A preprint of this manuscript is available on research square (doi: 10.21203/rs.3.rs-1857436/v1).


Assuntos
Infecções por Vírus Epstein-Barr , Doença de Hodgkin , Humanos , Doença de Hodgkin/complicações , Doença de Hodgkin/genética , Doença de Hodgkin/metabolismo , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/metabolismo , NF-kappa B/metabolismo , Antígeno B7-H1 , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/patologia , Ciclo-Oxigenase 2/metabolismo , Estudos Prospectivos , Transdução de Sinais , Prognóstico , RNA Mensageiro , Recidiva
11.
Stud Health Technol Inform ; 310: 850-854, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38269929

RESUMO

With increasing number of people living with dementia, the problem of late diagnosis significantly impacts a person's quality of life while early signs of dementia may provide useful insights to facilitate better treatment plans. With time, this progressive neurodegenerative syndrome could progress from mild cognitive impairment to dementia. A pattern of health conditions can be characterized in unsupervised manner to help predict this progress. As a significant extension to our previous work with streaming clustering model, we consider additional information for predicting dementia onset. With empirical observations, we discover the importance of examining sex and age to predict dementia onset. To this end, we propose a sex-specific model with age-constraint for predicting dementia onset and validate the effectiveness of our models using data from Mayo Clinic Study of Aging (MCSA). The proposed sex-specific models for older adult populations (>=65 years of age) outperformed the previous models with F-score of 77% and 78% for male-specific and female-specific models, respectively. Our experiments of sex-specific temporal clustering of features in older adults demonstrate the potential of more personalized models for early alerts of dementia.


Assuntos
Disfunção Cognitiva , Demência , Humanos , Feminino , Masculino , Idoso , Qualidade de Vida , Envelhecimento , Análise por Conglomerados , Disfunção Cognitiva/diagnóstico , Demência/diagnóstico
12.
Data Brief ; 51: 109782, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38053602

RESUMO

The security and privacy of wireless channels is typically enforced by leveraging cryptographic tools. However, there are scenarios where these methods are unfit, such as in resource-constrained environments, i.e., Internet of Things (IoT), or when an extra layer of security is needed. A promising solution involves correlating air pressure (barometric) readings to securely pair IoT devices while requiring zero-interaction. This paper presents an experimental dataset of real-world barometric measurements collected in open areas under different weather conditions. Specifically, our dataset includes readings recorded using the reference hardware platform BMP280. The experiments involve a reference scenario constituted by three Adafruit BMP280 barometric sensors connected to a Raspberry Pi 3 Model B board to collect barometric measurements. The three sensors represent two communicating parties (Alice and Bob) and an adversary (Eve), respectively. The dataset is constituted by three experiments characterized by different relative distances among Alice, Bob, and Eve. We considered 5cm and 2m between Alice and Bob while placing Eve at 2m and 8 meters, respectively. The second configuration, i.e., (Alice-Bob at 2m and Eve at 8m) has been replicated in a different scenario characterized by less air pressure fluctuations. The sampling frequency has been set to 70Hz while the measurements last for 50, 24 and 41 hours, respectively. Researchers can use this dataset in several ways, including: (i) Study the air pressure variation and correlation between devices separated by different distances, (ii) Develop a co-location verification extension for the Diffie-Hellman (DH) key agreement method that utilizes air pressure data streams, (iii) Study possible attacks against proximity-based authentication techniques that depend on pressure correlated variations.

13.
PeerJ ; 11: e16256, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38152345

RESUMO

Salinity stress poses a major challenge to agricultural productivity worldwide, and understanding their responses at the early growth stage is vital for devising strategies to cope with this stress. Therefore, to improve triticale productivity, this study investigated the salinity stress tolerance of different salt-tolerant triticale genotypes aiming to cultivate them on saline soils. To this end, salinity stress impacts on nine triticale genotypes, i.e., Zhongsi 1084, Gannong No. 2, Gannong No. 4, Shida No. 1, C6, C16, C23, C25 and C36 at germination and early seedling stages was evaluated. Each genotype was subjected to six treatments inducing control, 40, 80, 120, 160, and 200 mM NaCl treatments to study their effect on seedling and termination traits of the nine genotypes. Compared to the overall mean seedling vigor index, the seedling vigor index was higher in the genotypes Zhongsi 1084 and C6 (39% and 18.1%, respectively) and lower in Gannong No.2 (41%). Increasing NaCl concentrations negatively affected germination and seedling traits. Compared to other genotypes, Zhongsi 1084 had the highest mean germination rate, germination vigor index, germination percentage, mean daily germination and germination energy. It also showed the lowest relative salt injury. The relative salt injury was higher in the genotype Shida No. 1 than those in Gannong No. 2, Gannong No. 4, Shida No. 1, C16, and C36 genotypes. All genotypes exhibited desirable mean germination time except for line C6. High significant positive correlations were observed among germination rate, germination vigor index, germination percentage, mean daily germination, seedling vigor index, and root length. Principal component analysis (PCA) grouped the most desirable genotypes into two clusters. Our study determined salt stress tolerance of nine triticale genotypes at germination and early seedling stages. to select salt-tolerant genotypes that can be cultivated on saline soil or after salt irrigation.


Assuntos
Plântula , Triticale , Plântula/genética , Germinação/genética , Cloreto de Sódio/farmacologia , Solo , Genótipo
14.
Int J Mol Sci ; 24(21)2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37958509

RESUMO

Doxorubicin (DOX), which is used to treat cancer, has harmful effects that limit its therapeutic application. Finding preventative agents to thwart DOX-caused injuries is thus imperative. Artemisia annua has numerous biomedical uses. This study aims to investigate the attenuative effect of Artemisia annua leaf extract (AALE) treatment on DOX-induced hepatic toxicity in male rats. A phytochemical screening of AALE was evaluated. Forty male rats were used; G1 was a negative control group, G2 was injected with AALE (150 mg/kg) intraperitoneally (i.p) daily for a month, 4 mg/kg of DOX was given i.p to G3 once a week for a month, and G4 was injected with DOX as G3 and with AALE as G2. Body weight changes and biochemical, molecular, and histopathological investigations were assessed. The results showed that AALE contains promising phytochemical constituents that contribute to several potential biomedical applications. AALE mitigated the hepatotoxicity induced by DOX in rats as evidenced by restoring the alterations in the biochemical parameters, antioxidant gene expression, and hepatic histopathological alterations in rats. Importantly, the impact of AALE against the hepatic deterioration resulting from DOX treatment is through activation of the PI-3K/Akt/Nrf-2 signaling, which in turn induces the antioxidant agents.


Assuntos
Antioxidantes , Artemisia annua , Ratos , Masculino , Animais , Antioxidantes/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Artemisia annua/química , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Doxorrubicina/efeitos adversos , Compostos Fitoquímicos/farmacologia , Estresse Oxidativo
15.
Nature ; 623(7986): 432-441, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37914932

RESUMO

Chromatin accessibility is essential in regulating gene expression and cellular identity, and alterations in accessibility have been implicated in driving cancer initiation, progression and metastasis1-4. Although the genetic contributions to oncogenic transitions have been investigated, epigenetic drivers remain less understood. Here we constructed a pan-cancer epigenetic and transcriptomic atlas using single-nucleus chromatin accessibility data (using single-nucleus assay for transposase-accessible chromatin) from 225 samples and matched single-cell or single-nucleus RNA-sequencing expression data from 206 samples. With over 1 million cells from each platform analysed through the enrichment of accessible chromatin regions, transcription factor motifs and regulons, we identified epigenetic drivers associated with cancer transitions. Some epigenetic drivers appeared in multiple cancers (for example, regulatory regions of ABCC1 and VEGFA; GATA6 and FOX-family motifs), whereas others were cancer specific (for example, regulatory regions of FGF19, ASAP2 and EN1, and the PBX3 motif). Among epigenetically altered pathways, TP53, hypoxia and TNF signalling were linked to cancer initiation, whereas oestrogen response, epithelial-mesenchymal transition and apical junction were tied to metastatic transition. Furthermore, we revealed a marked correlation between enhancer accessibility and gene expression and uncovered cooperation between epigenetic and genetic drivers. This atlas provides a foundation for further investigation of epigenetic dynamics in cancer transitions.


Assuntos
Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Neoplasias , Humanos , Hipóxia Celular , Núcleo Celular , Cromatina/genética , Cromatina/metabolismo , Elementos Facilitadores Genéticos/genética , Epigênese Genética/genética , Transição Epitelial-Mesenquimal , Estrogênios/metabolismo , Perfilação da Expressão Gênica , Proteínas Ativadoras de GTPase/metabolismo , Metástase Neoplásica , Neoplasias/classificação , Neoplasias/genética , Neoplasias/patologia , Sequências Reguladoras de Ácido Nucleico/genética , Análise de Célula Única , Fatores de Transcrição/metabolismo
16.
Cureus ; 15(9): e46133, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37900416

RESUMO

BACKGROUND: Thyroid diseases can affect various bodily functions and often go unnoticed. Tools such as sonography and fine needle aspiration (FNA) puncture are necessary to diagnose diseases that require surgical intervention. These tools help identify signs of malignancy or benignity and obtain further data to guide therapeutic decisions. This study aims to validate the relationship between sonographic results, FNA, and final thyroid pathology. This research describes the level of correlation between sonographic findings and FNA, the sonographic and final pathology reports, and the FNA and final pathology reports. Additionally, this research aims to identify the most common diagnoses in the final pathology. METHODS: A retrospective descriptive observational study was carried out with a sample of 95 patients who underwent thyroid surgery at the National Institute of Diabetes, Endocrinology, and Nutrition (INDEN), Dominican Republic, in 2019 to determine whether a relationship exists between the sonography findings, FNA, and the final pathology in surgical thyroid pathologies. RESULTS: A total of 95 patients were studied. The success rate of the sonography results compared with the benign final biopsy result was 100% and 45.9% with the malignant final biopsy result. The success rate of the fine needle biopsy results was 95.9% for the benign final biopsy and 28% for the malignant final biopsy. Of the malignant final biopsy reports, 84.6% were papillary carcinomas, 7.7% were follicular carcinomas, and 7.7% were medullary carcinomas. CONCLUSIONS: The relationship between the sonographic results, FNA, and histopathological findings of surgical thyroid diseases is validated. The sonographic findings are specific for diagnosing benignity and malignancy. A fine needle biopsy is useful for diagnosing benignity, and the final biopsy is the standard for confirming both benign and malignant pathologies.

17.
Internet Interv ; 34: 100666, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37746637

RESUMO

Background: Advances in smartphone technology have allowed people to access mental healthcare via digital apps from wherever and whenever they choose. University students experience a high burden of mental health concerns. Although these apps improve mental health symptoms, user engagement has remained low. Studies have shown that users can be subgrouped based on unique characteristics that just-in-time adaptive interventions (JITAIs) can use to improve engagement. To date, however, no studies have examined the effect of the COVID-19 pandemic on these subgroups. Objective: Here, we sought to examine user subgroup characteristics across three COVID-19-specific timepoints: during lockdown, immediately following lockdown, and three months after lockdown ended. Methods: To do this, we used a two-step machine learning approach combining unsupervised and supervised machine learning. Results: We demonstrate that there are three unique subgroups of university students who access mental health apps. Two of these, with either higher or lower mental well-being, were defined by characteristics that were stable across COVID-19 timepoints. The third, situational well-being, had characteristics that were timepoint-dependent, suggesting that they are highly influenced by traumatic stressors and stressful situations. This subgroup also showed feelings and behaviours consistent with burnout. Conclusions: Overall, our findings clearly suggest that user subgroups are unique: they have different characteristics and therefore likely have different mental healthcare goals. Our findings also highlight the importance of including questions and additional interventions targeting traumatic stress(ors), reason(s) for use, and burnout in JITAI-style mental health apps to improve engagement.

18.
BMC Plant Biol ; 23(1): 388, 2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37563704

RESUMO

BACKGROUND: Stripe rust is considered one of the most devastating diseases of wheat all over the world, resulting in a high loss in its production. In this study, time-course changes in expression of the polyphenol biosynthesis pathways genes in wheat against stripe rust were investigated. The defense mechanisms triggered by mycorrhizal colonization and/or spraying with Streptomyces viridosporus HH1 against this disease were also investigated. RESULTS: Results obtained revealed that C3H, which is considered the key gene in lignin biosynthesis, was the most expressed gene. Furthermore, most of the chlorogenic acid and flavonoid biosynthesis genes were also overexpressed. Volcano plots of the studied genes reveal that the dual treatment led to a high significant overexpression of 10 out of the 13 studied genes. Heatmap of these genes showed that the most frequent expressed gene in response to all applied treatments along the study period was DFR, the key gene in the biosynthesis of anthocyanidins. Gene co-expression network of the studied genes showed that HQT was the most central gene with respect to the other genes, followed by AN2 and DFR, respectively. Accumulation of different flavonoids and phenolic acids were detected in response to the dual treatment, in particular, cinnamic acid, coumarin, and esculetin, which recorded the highest elevation level recording 1000, 488.23, and 329.5% respectively. Furthermore, results from the greenhouse experiment showed that application of the dual treatment led to an 82.8% reduction in the disease severity, compared with the control treatment. CONCLUSIONS: We can conclude that the biosynthesis of lignin, chlorogenic acid, and flavonoids contributed to the synergistic triggering effect of the dual treatment on wheat resistance to stripe rust.


Assuntos
Basidiomycota , Micorrizas , Triticum/genética , Polifenóis , Ácido Clorogênico , Lignina , Basidiomycota/fisiologia , Flavonoides , Doenças das Plantas/genética , Resistência à Doença/genética
19.
Materials (Basel) ; 16(15)2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37569911

RESUMO

This paper is devoted to the determination of the coefficient of friction (COF) in the drawbead region in metal forming processes. As the test material, AW-5251 aluminium alloys sheets fabricated under various hardening conditions (AW-5251-O, AW-5251-H14, AW-5251-H16 and AW-5251H22) were used. The sheets were tested using a drawbead simulator with different countersample roughness and different orientations of the specimens in relation to the sheet rolling direction. A drawbead simulator was designed to model the friction conditions when the sheet metal passed through the drawbead in sheet metal forming. The experimental tests were carried out under conditions of dry friction and lubrication of the sheet metal surfaces with three lubricants: machine oil, hydraulic oil, and engine oil. Based on the results of the experimental tests, the value of the COF was determined. The Random Forest (RF) machine learning algorithm and artificial neural networks (ANNs) were used to identify the parameters affecting the COF. The R statistical package software version 4.1.0 was used for running the RF model and neural network. The relative importance of the inputs was analysed using 12 different activation functions in ANNs and nine different loss functions in the RF. Based on the experimental tests, it was concluded that the COF for samples cut along the sheet rolling direction was greater than for samples cut in the transverse direction. However, the COF's most relevant input was oil viscosity (0.59), followed by the average counter sample roughness Ra (0.30) and the yield stress Rp0.2 and strength coefficient K (0.05 and 0.06, respectively). The hard sigmoid activation function had the poorest R2 (0.25) and nRMSE (0.30). The ideal run was found after training and testing the RF model (R2 = 0.90 ± 0.028). Ra values greater than 1.1 and Rp0.2 values between 105 and 190 resulted in a decreased COF. The COF values dropped to 9-35 for viscosity and 105-190 for Rp0.2, with a gap between 110 and 130 when the oil viscosity was added. The COF was low when the oil viscosity was 9-35, and the Ra was 0.95-1.25. The interaction between K and the other inputs, which produces a relatively limited range of reduced COF values, was the least relevant. The COF was reduced by setting the Rp0.2 between 105 and 190, the Ra between 0.95 and 1.25, and the oil viscosity between 9 and 35.

20.
BMJ Open Qual ; 12(2)2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37257915

RESUMO

The COVID-19 pandemic resulted in the cessation of approximately 75% of cardiac rehabilitation (CR) programmes worldwide. In March 2020, CR phase II (CRP2) services were stopped in Qatar. Multiple studies had shown safety, effectiveness, reduced cost of delivery and improved participation with hybrid CR. A multidisciplinary team reviewed various alternative models for delivery and decided to implement a hybrid CRP2 exercise programme (HCRP2-EP) to ensure continuation of our patient care. Our aim was to enrol in the HCRP2-EP 70% of all eligible patients by 30 September 2020. Institute for Health Care Improvement's collaborative model was adopted. Multiple plan-do-study-act cycles were used to test change ideas. The outcomes of the project were analysed using standard run chart rules to detect the changes in outcomes over time. This project was implemented from March 2020, and the male patients enrolled between August 2020 and April 2021, with sustained monthly median enrolment above target of 70% throughout. As for our secondary outcome, 75.8% of the male patients who completed HCRP2-EP showed a meaningful change in peak exercise capacity of ≥10% (mean change 17%±6%). There were no major adverse events reported, and the median Patient Satisfaction Score was 96% well above the institutional target of 90%. This shows a well-designed quality improvement programme is an appropriate strategy for implementing HCRP2-EP in a clinical setting, and HCRP2-EP is a feasible, effective and safe intervention in eligible male patients with cardiovascular disease.


Assuntos
COVID-19 , Reabilitação Cardíaca , Humanos , Masculino , Reabilitação Cardíaca/métodos , Pandemias , Melhoria de Qualidade , Terapia por Exercício
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