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BACKGROUND: Despite available clinical management strategies, chronic kidney disease (CKD) is associated with severe morbidity and mortality worldwide, which beckons new solutions. Host-microbial interactions with a depletion of Faecalibacterium prausnitzii in CKD are reported. However, the mechanisms about if and how F prausnitzii can be used as a probiotic to treat CKD remains unknown. METHODS: We evaluated the microbial compositions in 2 independent CKD populations for any potential probiotic. Next, we investigated if supplementation of such probiotic in a mouse CKD model can restore gut-renal homeostasis as monitored by its effects on suppression on renal inflammation, improvement in gut permeability and renal function. Last, we investigated the molecular mechanisms underlying the probiotic-induced beneficial outcomes. RESULTS: We observed significant depletion of Faecalibacterium in the patients with CKD in both Western (n=283) and Eastern populations (n=75). Supplementation of F prausnitzii to CKD mice reduced renal dysfunction, renal inflammation, and lowered the serum levels of various uremic toxins. These are coupled with improved gut microbial ecology and intestinal integrity. Moreover, we demonstrated that the beneficial effects in kidney induced by F prausnitzii-derived butyrate were through the GPR (G protein-coupled receptor)-43. CONCLUSIONS: Using a mouse CKD model, we uncovered a novel beneficial role of F prausnitzii in the restoration of renal function in CKD, which is, at least in part, attributed to the butyrate-mediated GPR-43 signaling in the kidney. Our study provides the necessary foundation to harness the therapeutic potential of F prausnitzii for ameliorating CKD.
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Faecalibacterium prausnitzii , Insuficiência Renal Crônica , Animais , Butiratos/farmacologia , Butiratos/uso terapêutico , Modelos Animais de Doenças , Inflamação , Rim/fisiologia , Receptores Acoplados a Proteínas G/genéticaRESUMO
There is no doubt that extreme contexts (e.g., war zones and pandemics) represent substantial disruptions that force many companies to rethink the way they do business. With so much of the workforce now working remotely and concerns about resulting work alienation, we must ask this question: How can this be translated into the generational divide in workplaces based in extreme contexts? Using COVID-19 as an example trigger of extreme-context experience, therefore, we investigate generation as a moderator of the effects of extreme-context perception upon anxiety leading to alienation with subsequent behavioral outcomes on job insecurity, job satisfaction, and organizational citizenship behavior (OCB). A time-lagged survey procedure yielded 219 valid responses from a three-generation sample of employees working in multiple service organizations. The data were analyzed using partial least squares structural equation modeling (PLS-SEM). Our analysis suggested that intense extreme-context perception led to elevated anxiety and alienation, which, in turn, heightened job insecurity and worsened job satisfaction and OCB outcomes. Finally, during the experience of extreme-context times, generation was found to moderate our model, such that both Generation Y and Generation Z experienced higher anxiety due to extreme-context perception and hence higher job insecurity due to alienation compared with Generation X respondents. Our results endorse the criticality of implementing agile and generationally non-sectarian management for effectively functioning generationally diverse workforces in pandemic times.
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Teletrabalho , Local de Trabalho , Humanos , Satisfação no Emprego , Emoções , PercepçãoRESUMO
Facebook is one of the most popular social networking sites. However, Facebook intrusion or addiction is a growing concern as it involves an excessive attachment to Facebook, which disrupts daily functioning. To date, few studies have examined whether cross-cultural differences in the measurement of Facebook addiction exist. The aim of this study was to investigate the cross-cultural validity and measurement invariance of the Facebook Intrusion Questionnaire (FIQ), one of the most widely used measures of Facebook addiction, across 25 countries (N = 12,204, 62.3% female; mean age = 25 years). Multigroup confirmatory factor analyses (MGCFA) assessed cross-cultural validity as well as invariance. Additionally, individual confirmatory factor analyses evaluated the factorial structure and measurement invariance across genders in each country. The FIQ demonstrated partial metric invariance across countries and metric (13 countries), scalar (11 countries) or residual (10 countries) invariance across genders within individual countries. A one-factor model indicated a good fit in 18 countries. Cronbach's alpha for the entire sample was .85. Our findings suggest that the FIQ may provide an adequate assessment of Facebook addiction that is psychometrically equivalent across cultures. Moreover, the questionnaire seems to be universal and suitable for studying different social media in distinct cultural environments. Consequently, this robust tool can be used to explore behaviours related to specific media that are particularly popular in any given country.
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Background and Objectives: Urinary tract infections [UTIs] are considered the third most known risk of infection in human health around the world. There is increasing appreciation for the pathogenicity of Gram-positive and Gram-negative strains in UTIs, aside from fungal infection, as they have numerous virulence factors. Materials and Methods: In this study, fifty urine samples were collected from patients suffering from UTI. Among the isolates of UTI microbes, six isolates were described as MDR isolates after an antibiotic susceptibility test carried out using ten different antibiotics. An alternative treatment for microbial elimination involved the use of biosynthesized silver nanoparticles (AgNPs) derived from Solanum lycopersicum [S. cumin]. Results: The sizes and shapes of AgNPs were characterized through TEM imaging, which showed spherical particles in a size range of 35-80 nm, of which the average size was 53 nm. Additionally, the silver nanoparticles (AgNPs) demonstrated inhibitory activity against Staphylococcus aureus (OR648079), exhibiting a 31 mm zone of inhibition at a minimum inhibitory concentration (MIC) of 4 mg/mL and a minimum bactericidal concentration (MBC) of 8 mg/mL. This was followed by Aspergillus niger (OR648075), which showed a 30 mm inhibition zone at an MIC of 16 mg/mL and a minimum fungicidal concentration (MFC) of 32 mg/mL. Then, Enterococcus faecalis (OR648078), Klebsiella pneumoniae (OR648081), and Acinetobacter baumannii (OR648080) each displayed a 29 mm zone of inhibition at an MIC of 8 mg/mL and an MBC of 16 mg/mL. The least inhibition was observed against Candida auris (OR648076), with a 25 mm inhibition zone at an MIC of 16 mg/mL and an MFC of 32 mg/mL. Furthermore, AgNPs at different concentrations removed DPPH and H2O2 at an IC50 value of 13.54 µg/mL. Also, AgNPs at 3 mg/mL showed remarkable DNA fragmentation in all bacterial strains except Enterococcus faecalis. The phytochemical analysis showed the presence of different active organic components in the plant extract, which concluded that rutin was 88.3 mg/g, garlic acid was 70.4 mg/g, and tannic acid was 23.7 mg/g. Finally, AgNPs concentrations in the range of 3-6 mg/mL showed decreased expression of two of the fundamental genes necessary for biofilm formation within Staphylococcus aureus, fnbA (6 folds), and Cna (12.5 folds) when compared with the RecA gene, which decreased by one-fold when compared with the control sample. These two genes were submitted with NCBI accession numbers [OR682119] and [OR682118], respectively. Conclusions: The findings from this study indicate that biosynthesized AgNPs from Solanum lycopersicum exhibit promising antimicrobial and antioxidant properties against UTI pathogens, including strains resistant to multiple antibiotics. This suggests their potential as an effective alternative treatment for UTIs. Further research is warranted to fully understand the mechanisms of action and to explore the therapeutic applications of these nanoparticles in combating UTIs.
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Adesinas Bacterianas , Anti-Infecciosos , Nanopartículas Metálicas , Polifenóis , Solanum lycopersicum , Humanos , Prata/farmacologia , Antioxidantes/farmacologia , Virulência , Nanopartículas Metálicas/uso terapêutico , Peróxido de Hidrogênio/farmacologia , Anti-Infecciosos/farmacologia , Antibacterianos/farmacologia , Staphylococcus aureus , Biofilmes , Anti-Inflamatórios/farmacologiaRESUMO
Graphitic carbon nitride (g-C3 N4 ) has gained tremendous interest in the sector of power transformation and retention, because of its distinctive stacked composition, adjustable electronic structure, metal-free feature, superior thermodynamic durability, and simple availability. Furthermore, the restricted illumination and extensive recombination of photoexcitation electrons have inhibited the photocatalytic performance of pure g-C3 N4 . The dimensions of g-C3 N4 may impact the field of electronics confinement; as a consequence, g-C3 N4 with varying dimensions shows unique features, making it appropriate for a number of fascinating uses. Even if there are several evaluations emphasizing on the fabrication methods and deployments of g-C3 N4 , there is certainly an insufficiency of a full overview, that exhaustively depicts the synthesis and composition of diverse aspects of g-C3 N4 . Consequently, from the standpoint of numerical simulations and experimentation, several legitimate methodologies were employed to deliberately develop the photocatalyst and improve the optimal result, including elements loading, defects designing, morphological adjustment, and semiconductors interfacing. Herein, this evaluation initially discusses different dimensions, the physicochemical features, modifications and interfaces design development of g-C3 N4 . Emphasis is given to the practical design and development of g-C3 N4 for the various power transformation and inventory applications, such as photocatalytic H2 evolution, photoreduction of CO2 source, electrocatalytic H2 evolution, O2 evolution, O2 reduction, alkali-metal battery cells, lithium-ion batteries, lithium-sulfur batteries, and metal-air batteries. Ultimately, the current challenges and potential of g-C3 N4 for fuel transformation and retention activities are explored.
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In spite of the huge advancements in both diagnosis and interventions, hormone refractory prostate cancer (HRPC) remains a major hurdle in prostate cancer (PCa). Metabolic reprogramming plays a key role in PCa oncogenesis and resistance. However, the dynamics between metabolism and oncogenesis are not fully understood. Here, we demonstrate that two multi-target natural products, cannabidiol (CBD) and cannabigerol (CBG), suppress HRPC development in the TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model by reprogramming metabolic and oncogenic signaling. Mechanistically, CBD increases glycolytic capacity and inhibits oxidative phosphorylation in enzalutamide-resistant HRPC cells. This action of CBD originates from its effect on metabolic plasticity via modulation of VDAC1 and hexokinase II (HKII) coupling on the outer mitochondrial membrane, which leads to strong shifts of mitochondrial functions and oncogenic signaling pathways. The effect of CBG on enzalutamide-resistant HRPC cells was less pronounced than CBD and only partially attributable to its action on mitochondria. However, when optimally combined, these two cannabinoids exhibited strong anti-tumor effects in TRAMP mice, even when these had become refractory to enzalutamide, thus pointing to their therapeutical potential against PCa.
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Canabidiol , Neoplasias da Próstata , Humanos , Masculino , Camundongos , Animais , Canabidiol/farmacologia , Morte Celular , Mitocôndrias/metabolismo , Neoplasias da Próstata/metabolismo , Fosforilação Oxidativa , Carcinogênese/metabolismo , Hormônios/metabolismo , Canal de Ânion 1 Dependente de Voltagem/metabolismoRESUMO
Lipids are either taken up from food sources or produced internally in specialized tissues such as the liver. Among others, both routes of lipid metabolism involve cytochrome P450 monooxygenases (CYPs). We sought to analyze the function of Cyp311a1 that has been shown to be expressed in the midgut of the fruit fly Drosophila melanogaster. Using a GFP-tagged version of CYP311A1 that is expressed under the control of its endogenous promoter, we show that Cyp311a1 localizes to the endoplasmic reticulum in epithelial cells of the anterior midgut. In larvae with reduced Cyp311a1 expression in the anterior midgut, compared to control larvae, the apical plasma membrane of the respective epithelial cells contains less and shorter microvilli. In addition, we observed reduction of neutral lipids in the fat body, the insect liver, and decreased phosphatidylethanolamine (PE) and triacylglycerols (TAG) amounts in the whole body of these larvae. Probably as a consequence, they cease to grow and eventually die. The microvillus defects in larvae with reduced Cyp311a1 expression are restored by supplying PE, a major phospholipid of plasma membranes, to the food. Moreover, the growth arrest phenotype of these larvae is partially rescued. Together, these results suggest that the anterior midgut is an import hub in lipid distribution and that the midgut-specific CYP311A1 contributes to this function by participating in shaping microvilli in a PE-dependent manner.
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Drosophila melanogaster , Lipídeos , Animais , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Larva , MicrovilosidadesRESUMO
Hemangioblastoma is a rare benign tumor that can affect the central nervous system sporadically or in association with von Hippel-Lindau (VHL) syndrome. Despite the advances in the medical field, hemangioblastoma still has a significant morbidity and mortality burden. This review gathered and analyzed this entity's top one hundred cited articles. The Scopus database was screened using the following keywords ("Hemangioblastoma" OR "Haemangioblastoma" OR "Hemangioblastomata"). The results were sorted by citation count, highest to lowest. Articles discussing hemangioblastoma of the central nervous system were included. Two independent reviewers extracted the article-, author-, and Journal-based data. Articles were classified into four categories: clinical features/ natural history, treatment, histopathology, review, or radiology. The location, brain, spine, or both, and type, sporadic, VHL-associated, or both, were used to classify the articles. The search query resulted in 4023 articles, and the top 100 most cited articles were included. The number of citations totaled 8781, averaging 87.81 CC per article. The included papers were published in 41 different journals between 1952 and 2014 by more than 11 departments from 65 institutions and 16 countries. The number of citations ranged from 46 to 333. The peak publication activity was before the 2000s, contributing to 62% of all articles, and the most prolific decade was 1990-2000, with 37 publications. We conducted a comprehensive bibliometric analysis of data from the most influential publications on central nervous system hemangioblastoma. We identified publication dynamics and research gaps. More high-impact studies are warranted to enhance disease comprehension and management.
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Neoplasias do Sistema Nervoso Central , Hemangioblastoma , Doença de von Hippel-Lindau , Humanos , Bibliometria , Hemangioblastoma/cirurgia , Hemangioblastoma/patologia , Neoplasias do Sistema Nervoso Central/cirurgia , Encéfalo/patologiaRESUMO
OBJECTIVE: Readmission after vascular procedures is a burden to hospitals and the Medicare system. Therefore, identifying risk factors leading to readmission is vital. We examined the frequency of and risk factors for 30-day readmission after open aneurysm repair (OAR) and explored post-operative outcomes with special attention for those with preexisting chronic kidney disease (CKD). METHODS: Patients who underwent OAR were identified in the National Readmission Database (2016-2018). Demographic information and comorbidities were collected. Patients readmitted within 30 days after their index hospitalization were identified and compared to patients without readmission records. RESULTS: A total of 5090 patients underwent OAR during the study timeframe with 488 patients (9.6%) were readmitted within 30 days. Females were more readmitted than males (F = 11.1% vs M = 9.0%, P < 0.001). Readmitted patients had more comorbidities (median ECI 12, P < 0.05), were on Medicare (73.7%, P < 0.001), had higher surgery admission cost ($146,844, P < 0.001), longer length of stay (8 days, P < 0.001), and were discharged to a lower level care facility (62.7%, P < 0.001). Comorbidities that predisposed patients for readmission include: peripheral arterial disease (OR 2.15, P < 0.01), asthma (OR 1.87, P < 0.01), chronic heart failure (OR 1.74, P < 0.05). On readmission visit, acute renal failure (23.8%) was the most common diagnosis, while intestinal surgery (13.7%) was the most common procedure. Patients with CKD (n = 968, 18.9% of total population) had double the mortality rate compared to non-CKD patients on surgery admission (10.4%, P < 0.001) and readmission (10.1%, P < 0.001). CONCLUSION: Certain factors were noted to increase readmission rate, special attention need to be paid when dealing with such group of patients requiring OAR. Vascular surgeons should meticulously weigh benefits and risks when considering OAR in patients with CKD who are not a candidate for endovascular repair, and optimize their kidney function before considering such approach.
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Aneurisma da Aorta Abdominal , Procedimentos Endovasculares , Insuficiência Renal Crônica , Masculino , Feminino , Humanos , Idoso , Estados Unidos/epidemiologia , Readmissão do Paciente , Resultado do Tratamento , Medicare , Fatores de Risco , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/cirurgia , Aneurisma da Aorta Abdominal/epidemiologia , Insuficiência Renal Crônica/diagnóstico , Procedimentos Endovasculares/efeitos adversos , Estudos Retrospectivos , Complicações Pós-Operatórias/etiologiaRESUMO
AIM: The aim of this study was to investigate the relationship between nurses' job crafting, organizational identification, and work attachment. BACKGROUND: Job crafting is a proactive activity in which nurses adapt the physical, cognitive, or social aspects of their jobs to make them more meaningful. Nurses are considered fundamental healthcare stakeholders who are able to transform initiatives implemented by the healthcare organization into valuable work outcomes. Nurses' perceptions of their jobs shape the community's opinion toward an organization. METHODS: This is a descriptive correlational study. Two hundred seventy nurses were recruited from 1 governmental hospital in Egypt. Respondents completed the self-administered, printed questionnaires. Measures included job crafting, organizational identification, and work attachment questionnaires. Findings were investigated via descriptive and inferential statistics. RESULTS: Over half of the nurses reported a moderate level of job crafting, whereas none of the nurses reported a high level of organizational identification. More than half of the nurses reported low levels of work attachment. CONCLUSION: Job crafting is significantly related to nurses' organizational identification and work attachment.
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Enfermeiras e Enfermeiros , Recursos Humanos de Enfermagem Hospitalar , Humanos , Atitude do Pessoal de Saúde , Recursos Humanos de Enfermagem Hospitalar/psicologia , Satisfação no Emprego , Local de Trabalho/psicologia , Inquéritos e QuestionáriosRESUMO
The sustainable development of the hydropower megaproject (HM) is one of the critical components of sustainable water resources management. Hence, an accurate assessment of the impacts of social-economic-ecological losses (SEEL) on the sustainability of the HM system is of utmost importance. This study proposes an emergy-based sustainability evaluation model incorporating the social-economic-ecological losses (ESM-SEEL), which integrated the inputs and outputs during HM's construction and operation into an emergy calculation account. The Three Gorges Project (TGP) on the Yangtze River is selected as a case study to comprehensively evaluate the HM's sustainability from 1993 to 2020. Subsequently, the emergy-based indicators of TGP are compared with several hydropower projects in China and worldwide to analyze the multi-impacts of hydropower development. The results showed that the river chemical potential (2.35 E+24sej) and the emergy losses (L) (1.39 E+24sej) are the primary emergy inflow sections (U) of the TGP system, accounting for 51.1% and 30.4% of the U, respectively. The flood control function of the TGP produced tremendous socio-economic benefits (1.24 E+24sej), accounting for 37.8% of the total emergy yield. The resettlement and compensation, water pollution during operation, fish biodiversity loss, and sediment deposition are the main L of the TGP, accounting for 77.8%, 8.4%, 5.6%, and 2.6%, respectively. Based on the enhanced emergy-based indicators, the assessment reveals that the sustainability level of the TGP falls in the middle range compared to other hydropower projects. Thus, along with maximizing the benefits of the HM system, it is necessary to minimize the SEEL of the HM system, which is a critical approach to promote the coordinated development of the hydropower and ecological environment in the Yangtze River basin. This study helps to understand the complex relationship between human and water systems and provides a novel framework that can be used as an evaluation index and insights for hydropower sustainability assessment.
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Conservação dos Recursos Naturais , Ecossistema , Humanos , Conservação dos Recursos Naturais/métodos , Poluição da Água , ChinaRESUMO
INTRODUCTION: Nonthyroidal illness syndrome (NTIS) is common in hemodialysis patients (HPs). However, limited clinical trials have been conducted in this field. Therefore, the aim of this study was to investigate the effect of Se and/or N-acetyl-cysteine (NAC) on NTIS parameters in HPs. METHODS: In this factorial randomized controlled trial, 68 HPs were divided into four groups: group A received placebo of Se and NAC, group B received 600 µg per day of NAC and placebo of Se, group C received 200 µg of Se per day and placebo of NAC and group D received 200 µg of selenium and 600 µg of NAC per day for 12 weeks. Blood samples were taken at baseline and after 12 weeks to assess free tri-iodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), and reverse T3 (rT3) concentrations. RESULTS: Our finding demonstrated that rT3 levels were decreased in B, C, and D groups and increased nearly to baseline levels in the A group after 12 weeks, with a marked difference between the groups (p < 0.001) based on ANOVA. Although there were no significant differences in FT3 (p = 0.39), FT4 (p = 0.76), and TSH (p = 0.71) between the groups at the end of the trial. CONCLUSION: This trial showed that Se and/or NAC exert beneficial effects on rT3 levels in HPs. However, long-term clinical trials with a larger sample size using more appropriate biomarkers are recommended to evaluate the efficacy and safety of Se and/or NAC in HPs.
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Selênio , Acetilcisteína/uso terapêutico , Suplementos Nutricionais , Humanos , Diálise Renal/efeitos adversos , Selênio/farmacologia , TireotropinaRESUMO
Sensors used to diagnose, monitor or treat diseases in the medical domain are known as medical sensors [...].
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Computadores , Diagnóstico por ComputadorRESUMO
Diabetic retinopathy (DR) is a devastating condition caused by progressive changes in the retinal microvasculature. It is a leading cause of retinal blindness in people with diabetes. Long periods of uncontrolled blood sugar levels result in endothelial damage, leading to macular edema, altered retinal permeability, retinal ischemia, and neovascularization. In order to facilitate rapid screening and diagnosing, as well as grading of DR, different retinal modalities are utilized. Typically, a computer-aided diagnostic system (CAD) uses retinal images to aid the ophthalmologists in the diagnosis process. These CAD systems use a combination of machine learning (ML) models (e.g., deep learning (DL) approaches) to speed up the diagnosis and grading of DR. In this way, this survey provides a comprehensive overview of different imaging modalities used with ML/DL approaches in the DR diagnosis process. The four imaging modalities that we focused on are fluorescein angiography, fundus photographs, optical coherence tomography (OCT), and OCT angiography (OCTA). In addition, we discuss limitations of the literature that utilizes such modalities for DR diagnosis. In addition, we introduce research gaps and provide suggested solutions for the researchers to resolve. Lastly, we provide a thorough discussion about the challenges and future directions of the current state-of-the-art DL/ML approaches. We also elaborate on how integrating different imaging modalities with the clinical information and demographic data will lead to promising results for the scientists when diagnosing and grading DR. As a result of this article's comparative analysis and discussion, it remains necessary to use DL methods over existing ML models to detect DR in multiple modalities.
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Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Retinopatia Diabética/diagnóstico por imagem , Angiofluoresceinografia/efeitos adversos , Humanos , Retina/diagnóstico por imagem , Tomografia de Coerência Óptica/métodosRESUMO
Prostate cancer, which is also known as prostatic adenocarcinoma, is an unconstrained growth of epithelial cells in the prostate and has become one of the leading causes of cancer-related death worldwide. The survival of patients with prostate cancer relies on detection at an early, treatable stage. In this paper, we introduce a new comprehensive framework to precisely differentiate between malignant and benign prostate cancer. This framework proposes a noninvasive computer-aided diagnosis system that integrates two imaging modalities of MR (diffusion-weighted (DW) and T2-weighted (T2W)). For the first time, it utilizes the combination of functional features represented by apparent diffusion coefficient (ADC) maps estimated from DW-MRI for the whole prostate in combination with texture features with its first- and second-order representations, extracted from T2W-MRIs of the whole prostate, and shape features represented by spherical harmonics constructed for the lesion inside the prostate and integrated with PSA screening results. The dataset presented in the paper includes 80 biopsy confirmed patients, with a mean age of 65.7 years (43 benign prostatic hyperplasia, 37 prostatic carcinomas). Experiments were conducted using different well-known machine learning approaches including support vector machines (SVM), random forests (RF), decision trees (DT), and linear discriminant analysis (LDA) classification models to study the impact of different feature sets that lead to better identification of prostatic adenocarcinoma. Using a leave-one-out cross-validation approach, the diagnostic results obtained using the SVM classification model along with the combined feature set after applying feature selection (88.75% accuracy, 81.08% sensitivity, 95.35% specificity, and 0.8821 AUC) indicated that the system's performance, after integrating and reducing different types of feature sets, obtained an enhanced diagnostic performance compared with each individual feature set and other machine learning classifiers. In addition, the developed diagnostic system provided consistent diagnostic performance using 10-fold and 5-fold cross-validation approaches, which confirms the reliability, generalization ability, and robustness of the developed system.
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Adenocarcinoma , Neoplasias da Próstata , Adenocarcinoma/diagnóstico por imagem , Idoso , Imagem de Difusão por Ressonância Magnética/métodos , Humanos , Masculino , Próstata/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Reprodutibilidade dos TestesRESUMO
Cannabinoid type 1 (hCB1) and type 2 (hCB2) receptors are pleiotropic and crucial targets whose signaling contributes to physiological homeostasis and its restoration after injury. Being predominantly expressed in peripheral tissues, hCB2R represents a safer therapeutic target than hCB1R, which is highly expressed in the brain, where it regulates processes related to cognition, memory, and motor control. The development of hCB2R ligands represents a therapeutic opportunity for treating diseases such as pain, inflammation and cancer. Identifying new selective scaffolds for cannabinoids and determining the structural determinants responsible for agonism and antagonism are priorities in drug design. In this work, a series of N-[1,3-dialkyl(aryl)-2-oxoimidazolidin-4-ylidene]-aryl(alkyl)sulfonamides is designed and synthesized and their affinity for human hCB1R and hCB2R is determined. Starting with a scaffold selected from the NIH Psychoactive Drug Screening Program Repository, through a combination of molecular modeling and structure-activity relationship studies, we were able to identify the chemical features leading to finely tuned hCB2R selectivity. In addition, an in silico model capable of predicting the functional activity of hCB2R ligands was proposed and validated. The proposed receptor activation/deactivation model enabled the identification of four pure hCB2R-selective agonists that can be used as a starting point for the development of more potent ligands.
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Agonistas de Receptores de Canabinoides , Canabinoides , Humanos , Ligação Proteica , Ligantes , Agonistas de Receptores de Canabinoides/química , Relação Estrutura-Atividade , Sulfonamidas , Receptor CB2 de Canabinoide , Receptor CB1 de CanabinoideRESUMO
BACKGROUND: The research aimed to formulate and test a model concerning COVID-19 perceptions effects on job insecurity and a set of psychosocial factors comprising anxiety, depression, job burnout and job alienation in the Middle East and North African (hereafter, MENA) regional context. Also, the study attempted to examine whether locus of control can moderate these hypothesised linkages amongst customer service employees working in MENA hospitality organisations. METHODS: The study is based on a sample of 885 responses to an online survey and Partial Least Square Structural Equation Modelling (PLS-SEM). RESULTS: The main findings show the existence of a significant correlation between COVID perceptions and job insecurity and all psychosocial factors, i.e., more intense COVID-19 perceptions accompany higher levels of job insecurity, anxiety, depression, job burnout and job alienation. Furthermore, our results revealed that, in pandemic time, hospitality customer service employees with external locus of control are more likely to suffer higher alienation, anxiety and depression than those with internal locus of control. CONCLUSIONS: The research originality centres on the establishment that COVID-19 has a severe negative impact within the hospitality customer service labour force (in the MENA region). These effects were more profound for participants who claimed external locus of control than those with internal locus of control.
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COVID-19 , Pandemias , Emprego , Humanos , Controle Interno-Externo , Satisfação no Emprego , Análise de Classes Latentes , Análise dos Mínimos Quadrados , Percepção , SARS-CoV-2RESUMO
BACKGROUND: This paper is an empirical investigation that examines a path model linking COVID-19 perceptions to organisational citizenship behaviour (OCBs) via three mediators: job insecurity, burnout, and job satisfaction. The research examines the path model invariance spanning Generations X, Y, and Z. Three countries in the Middle East and North Africa (MENA) were the focus of the study. METHODS: The data was collected from a sample of employees in service companies (n = 578). We used a Partial Least Square Structural Equation Modelling (PLS-SEM) to analyse the data. RESULTS: Our findings reveal that COVID-19 perceptions positively predict job insecurity, which positively impacts burnout levels. Burnout negatively predicts job satisfaction. The findings established that job satisfaction positively predicts OCBs. The mediation analysis determined that job insecurity, burnout and job satisfaction convey the indirect effects of COVID-19 perceptions onto OCBs. Finally, our hypothesised model is non-equivalent across Generations X, Y and Z. In that regard, our multi-group analysis revealed that the indirect effects of COVID-19 perceptions on OCBs were only valid amongst younger generations, i.e., Generation Y and Generation Z. Specifically, younger generations are substantially more vulnerable to the indirect effects of COVID-19 perceptions on their engagement in OCBs than Generation X whose job satisfaction blocks the effects of COVID-19 perceptions on OCBs. CONCLUSIONS: The present study extends our knowledge of workplace generational differences in responding to the perceptions of crises or pandemics. It offers evidence that suggests that burnout, job attitudes and organisational outcomes change differently across generations in pandemic times.
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Esgotamento Profissional , COVID-19 , Esgotamento Profissional/epidemiologia , Humanos , Satisfação no Emprego , Percepção , SARS-CoV-2 , Inquéritos e Questionários , Local de TrabalhoRESUMO
BACKGROUND: Shielding of high-risk groups from coronavirus disease (COVID-19) has been suggested as a realistic alternative to severe movement restrictions during the COVID-19 epidemic in low-income countries. The intervention entails the establishment of 'green zones' for high-risk persons to live in, either within their homes or in communal structures, in a safe and dignified manner, for extended periods of time during the epidemic. To our knowledge, this concept has not been tested or evaluated in resource-poor settings. This study aimed to explore the acceptability and feasibility of strategies to shield persons at higher risk of severe COVID-19 outcomes, during the COVID-19 epidemic in six communities in Sudan. METHODS: We purposively sampled participants from six communities, illustrative of urban, rural and forcibly-displaced settings. In-depth telephone interviews were held with 59 members of households with one or more members at higher risk of severe COVID-19 outcomes. Follow-up interviews were held with 30 community members after movement restrictions were eased across the country. All interviews were audio-recorded, transcribed verbatim, and analysed using a two-stage deductive and inductive thematic analysis. RESULTS: Most participants were aware that some people are at higher risk of severe COVID-19 outcomes but were unaware of the concept of shielding. Most participants found shielding acceptable and consistent with cultural inclinations to respect elders and protect the vulnerable. However, extra-household shielding arrangements were mostly seen as socially unacceptable. Participants reported feasibility concerns related to the reduced socialisation of shielded persons and loss of income for shielding families. The acceptability and feasibility of shielding strategies were reduced after movement restrictions were eased, as participants reported lower perception of risk in their communities and increased pressure to comply with social commitments outside the house. CONCLUSION: Shielding is generally acceptable in the study communities. Acceptability is influenced by feasibility, and by contextual changes in the epidemic and associated policy response. The promotion of shielding should capitalise on the cultural and moral sense of duty towards elders and vulnerable groups. Communities and households should be provided with practical guidance to implement feasible shielding options. Households must be socially, psychologically and financially supported to adopt and sustain shielding effectively.
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COVID-19 , Idoso , Surtos de Doenças , Estudos de Viabilidade , Humanos , SARS-CoV-2 , Sudão/epidemiologiaRESUMO
Pyrroles and its fused forms possess antimicrobial activities, they can easily interact with biomolecules of living systems. A series of substituted pyrroles, and its fused pyrimidines and triazines forms have been synthesised, all newly synthesised compound structures were confirmed by spectroscopic analysis. Generally, the compounds inhibited growth of some important human pathogens, the best effect was given by: 2a, 3c, 4d on Gram-positive bacteria and was higher on yeast (C. albicans), by 5c on Gram-negative bacteria and by 5a then 3c on filamentous fungi (A. fumigatus and F. oxysporum). Such results present good antibacterial and antifungal potential candidates to help overcome the global problem of antibiotic resistance and opportunistic infections outbreak. Compound 3c gave the best anti-phytopathogenic effect at a 50-fold lower concentration than Kocide 2000, introducing a safe commercial candidate for agricultural use. The effect of the compounds on DNA was monitored to detect the mode of action.