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The World Health Organization emphasizes the importance of providing integrated care for older people. Taiwan is the fastest aging country in the world. In 2016, Taiwan implemented the Long-Term Care Plan 2.0 (TLTCP 2.0), aimed at providing integrated long-term care (LTC) services in communities. However, LTC service agencies have not been able to evaluate the level of integrated care they provide due to the lack of an effective assessment tool. To address this need, this study sets out to develop an integration assessment tool, namely the Self-Assessment for Service Integration in Long-Term Care (SASI-LTC), which will allow LTC agencies to self-evaluate their current level of integration from multiple perspectives. The SASI-LTC was developed based on Evashwick's framework, underwent two rounds of Delphi panels with twenty-six experts, and a pilot test with 243 valid questionnaires from administrators of Tier A agencies who are responsible for integrating LTC. The Delphi experts assessed the content with high levels of agreement using medians, the scale content validity index (SCVI) and item content validity index (ICVI). The SASI-LTC included four domains (inter-entity organization and management, integrated care coordination, integrated resources, and integrated information systems) with thirty items. The SASI-LTC showed good reliability (Cronbach's α = 0.94) and good validity, and a confirmatory factor analysis showed a good model fit index [χ2/df = 1.38; RMSEA = 0.040; CFI = 0.963; SRMR = 0.049] in pilot testing. While the SASI-LTC is a useful and feasible tool for Taiwan's LTC service agencies to evaluate their level of integration in providing LTC services, it could also be used in other countries with minor adjustments to localization of items related to financial integration.
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OBJECTIVES: We assessed the relationship between social isolation and functional disability in older people. DESIGN: Comparison of longitudinal cohort studies. SETTING AND PARTICIPANTS: Harmonised longitudinal datasets from the United States, England, European countries, Japan, Korea, China and Hong Kong. METHODS: Social isolation was operationalised as a composite score with five domains, such as marital status, living alone, and social contact with others. Functional disability was defined as whether the cohort participant had any difficulty in activities of daily living (ADL). In each dataset, we used robust Poisson regression models to obtain the relative risks (RRs) and the corresponding 95 % confidence intervals (CI). We combined the RRs to synthesize a pooled estimate using meta-analysis with random-effects models. RESULTS: Overall, the social isolation composite score was not associated with ADL disability (pooled RR = 1.05, 95 % CI [0.97-1.14], n = 40,119). Subgroup analysis suggested social isolation composite score was associated with ADL disability in Asian regions (pooled RR = 1.09, 95 % CI [1.02, 1.16], but not in Western regions (pooled RR = 1.01, 95 % CI [0.96, 1.07]). The relationships between different domains of social isolation and ADL disability were heterogeneous, except that no participation in any social clubs or religious groups was consistently associated with ADL disability (pooled RR = 1.12, 95 % CI [1.04, 1.21]). CONCLUSION: Targeting social isolation may prevent decline in functional abilities in older adults, providing an avenue to active and healthy ageing. Nonetheless, interventions tackling social isolation should tailor to the unique cultural and social underpinnings. A limitation of the study is that reverse causality could not be ruled out definitively.
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Atividades Cotidianas , Pessoas com Deficiência , Isolamento Social , Humanos , Isolamento Social/psicologia , Atividades Cotidianas/psicologia , Idoso , Masculino , Feminino , Pessoas com Deficiência/psicologia , Pessoas com Deficiência/estatística & dados numéricos , Estudos Longitudinais , Estudos de Coortes , Idoso de 80 Anos ou mais , Avaliação da DeficiênciaRESUMO
PURPOSE: This study aimed to assess the prevalence and factors of physical, psychological, and social frailty among older adults in the emergency department, comparing these data with community population to understand emergency setting manifestations. METHODS: Conducted at the Emergency Department of National Taiwan University BioMedical Park Hospital, this prospective observational cohort study enrolled older adult patients over a three-month period. Frailty assessments included the Study of Osteoporotic Fractures scale for physical frailty, the Tilburg Frailty Indicator for psychological frailty, and the Makizako Social Frailty Index for social frailty. Data analysis involved a multivariable logistic model to determine the risk factors associated with each frailty type. RESULTS: Out of 991 older adult individuals seeking medical care, 207 participated in the study. The study found high prevalence rates of frailty: 46.38% for physical, 41.06% for psychological, and 48.79% for social frailty. Risk factors for frailty included older age and a history of falls. Interestingly, the prevalence of social frailty was notably higher than physical and psychological frailty. Gender and polypharmacy showed no significant association with any frailty type. CONCLUSION: This research reveals high physical, psychological, and social frailty among older ED patients, especially noting social frailty's prevalence. It highlights the importance for emergency care to adopt holistic care strategies that address older adults' multifaceted health challenges, suggesting a paradigm shift in current healthcare practices to better cater to the multifaceted needs of this vulnerable population.
RéSUMé: OBJECTIFS: Cette étude visait à évaluer la prévalence et les facteurs de la fragilité physique, psychologique et sociale chez les personnes âgées au service des urgences, en comparant ces données avec la population communautaire pour comprendre les manifestations en situation d'urgence. MéTHODES: Menée au service des urgences de l'hôpital BioMedical Park de l'Université nationale de Taiwan, cette étude prospective de cohorte observationnelle a recruté des patients adultes âgés sur une période de trois mois. Les évaluations de la fragilité comprenaient l'échelle de l'étude des fractures ostéoporotiques pour la fragilité physique, l'indicateur de la fragilité psychologique de Tilburg et l'indice de fragilité sociale de Makizako pour la fragilité sociale. L'analyse des données comportait un modèle logistique multivarié pour déterminer les facteurs de risque associés à chaque type de fragilité. RéSULTATS: Sur 991 personnes âgées ayant besoin de soins médicaux, 207 ont participé à l'étude. L'étude a révélé des taux de prévalence élevés de la fragilité : 46,38% pour le physique, 41,06% pour le psychologique et 48,79% pour la fragilité sociale. Les facteurs de risque de fragilité comprenaient un âge avancé et des antécédents de chute. Fait intéressant, la prévalence de la fragilité sociale était nettement plus élevée que la fragilité physique et psychologique. Le genre et la polypharmacie n'ont montré aucune association significative avec aucun type de fragilité. CONCLUSION: Cette recherche révèle une grande fragilité physique, psychologique et sociale chez les patients âgés aux urgences, en particulier la prévalence de la fragilité sociale. Il souligne l'importance pour les soins d'urgence d'adopter des stratégies de soins holistiques qui répondent aux défis de santé multiformes des personnes âgées, suggérant un changement de paradigme dans les pratiques de soins de santé actuelles pour mieux répondre aux besoins multiformes de cette population vulnérable.
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Compared to the number of studies on the neoplasms of laboratory rodents, fewer studies have focused on spontaneous neoplasms in pet rodents. Notably, the mouse mammary tumor virus (MMTV) is associated with mammary tumors in rodents. In this study, 77 tumors and tumor-like lesions of biopsy samples were collected from 70 pet rodents, including hamsters (n = 47), guinea pigs (n = 16), unknown species (n = 4), rats (n = 2), and a gerbil. Fifty tumors were collected from 47 hamsters, in which the most common tumors were mammary tumors (13/50), followed by fibrosarcoma (9/50), mast cell tumors (4/50), and squamous cell carcinoma (4/50). The collected subtypes of mammary tumors in hamsters included tubular carcinoma (n = 5), tubular adenoma (n = 4), carcinoma and malignant myoepithelioma (n = 1), simple tubular carcinoma (n = 1), adenosquamous carcinoma (n = 1), and tubulopapillary adenoma (n = 1). In addition, twenty tumors were collected from guinea pigs, in which the most common tumor was lipoma (6/20), followed by adenocarcinoma of the mammary gland (4/20), trichofolliculoma (2/20), and collagenous hamartomas (2/20). In guinea pigs, the subtypes of mammary gland tumors were tubular carcinoma (n = 2), tubular and solid carcinoma (n = 1), and tubulopapillary carcinoma (n = 1). In 20 cases of mammary tumors, MMTV was not detected, implicating no evidence of MMTV infection in mammary oncogenesis in pet rodents in Taiwan.
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BACKGROUND: This study aimed to assess family function in home care for older adults. Understanding family dynamics is essential for providing quality care to older adults choosing to age in place. METHODS: In a cross-sectional study, 53 patients aged 65 or older receiving home care were evaluated, along with four home care nurses. The General Function of Family Assessment Device (FAD-GF) was used for self-assessment to examine family resources. RESULTS: Only 5.7% of older adults reported good family function. Strong correlations were found between assessments by nurses and older adults. Among the six aspects of family function, "problem solving," "communication," "affective responsiveness," and the overall results showed no disparities between the evaluations of older adults and nurses. CONCLUSIONS: Home care nurses can effectively assess family function using the FAD-GF, particularly after six months of care. This assessment can help identify family issues and enhance home care quality through nurse training in FAD-GF application.
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Serviços de Assistência Domiciliar , Humanos , Estudos Transversais , Feminino , Idoso , Masculino , Idoso de 80 Anos ou mais , Relações Familiares/psicologia , Família/psicologiaRESUMO
The microbial degradation of polyethylene (PE) and polypropylene (PP) resins in rivers and lakes has emerged as a crucial issue in the management of microplastics. This study revealed that as the flow rate decreased longitudinally, ammonia nitrogen (NH4+-N), heavy fraction of organic carbon (HFOC), and small-size microplastics (< 1 mm) gradually accumulated in the deep and downstream estuarine sediments. Based on their surface morphology and carbonyl index, these sediments were identified as the potential hot zone for PE/PP degradation. Within the identified hot zone, concentrations of PE/PP-degrading genes, enzymes, and bacteria were significantly elevated compared to other zones, exhibiting strong intercorrelations. Analysis of niche differences revealed that the accumulation of NH4+-N and HFOC in the hot zone facilitated the synergistic coexistence of key bacteria responsible for PE/PP degradation within biofilms. The findings of this study offer a novel insight and comprehensive understanding of the distribution characteristics and synergistic degradation potential of PE/PP in natural freshwater environments.
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Bactérias , Biodegradação Ambiental , Sedimentos Geológicos , Polietileno , Polipropilenos , Poluentes Químicos da Água , Polipropilenos/química , Polietileno/química , Polietileno/metabolismo , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/química , Sedimentos Geológicos/microbiologia , Sedimentos Geológicos/química , Bactérias/metabolismo , Bactérias/genética , Microplásticos/toxicidade , Microplásticos/metabolismo , Água Doce/microbiologia , EstuáriosRESUMO
While 1q21+ was common genetic alteration and found to have adverse effect on prognosis, the underlying genes remain unclear. Identification of related genes may provide additional help for rational intervention. The microarray dataset GSE2658 associated with MM was downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were obtained, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to annotate their functions. The hub genes were derived from the combined results of up-regulated DEGs and weighted gene coexpression network analysis (WGCNA). The receiver operating characteristic (ROC) curves of hub genes were plotted to evaluate correlation with 1q21+. Survival analysis and drug-gene interaction of hub genes were performed separately to find the prognostic value and potential targeted drugs. A total of 55 DEGs were identified. GO and KEGG pathway analyses suggested that the DEGs were related to several pathways of cell proliferation. NVL, IL6R, DUSP23 were proven to be highly correlated with 1q21+ and have adverse effects on prognosis. IL6R, DUSP23 were matched to known interaction-drug. This study revealed potential roles of hub genes in the pathogenesis and progression of MM with 1q21+, further investigations are needed to elucidate the mechanisms.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Proliferação de Células , Biologia Computacional , Bases de Dados FactuaisRESUMO
BACKGROUND: Multiple role theory has proven effective in predicting variations in health, and a growing body of research has shown the importance of taking women's roles into account when analyzing physical activity levels. Nonetheless, researchers have yet to characterize the interaction between the various roles played by women and their physical activity. PURPOSE: The objectives of this study were to elucidate the relationship between multiple roles and leisure-time physical activities (LTPAs) and to determine whether LTPA varies among women across different roles. METHODS: Data were derived from the 2013 National Health Interview Survey database provided by the Health Promotion Administration of Taiwan's Ministry of Health and Welfare, which includes 5,147 working-age women. The current study focused on women aged 20-50 years. The roles considered in this study included living with a partner, living with children, and employment status. LTPA levels were categorized as regular, inactive, or insufficient based on the LTPA metabolic equivalent in the previous week. The associations among level of LTPA, multiple roles, and demographic characteristics were analyzed using multiple regression analysis. RESULTS: We found single mothers with children to be more inactive than partnered mothers, and women living with a partner and those living with children were more likely to be inactive, whereas women working full-time were not at risk of inactivity. Women who assumed a larger number of roles were at a greater risk of inactivity. These findings are consistent with role strain theory. CONCLUSIONS: Single mothers with children are more inactive than partnered mothers, and appropriate social support programs are necessary to reduce further disparities. Second, multiple demands on working-age women limit the time available for LTPAs, particularly among women living with a partner and children and engaged in full-time work. A physical activity intervention is a program or initiative designed to promote physical activity and improve health outcomes. We should develop and provide sustainable physical activity resources through the help of partners' housework to better promote physical activity intervention for working-age women.
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Exercício Físico , Atividades de Lazer , Criança , Humanos , Feminino , Mães , Inquéritos e Questionários , EmpregoRESUMO
Multidrug-resistant (MDR) bacteria are widespread in the environment and pose a serious threat to public health. It has been shown that bacteriocins have a great potential in controlling MDR pathogens, including Staphylococcus aureus. A previously reported Lactobacillus salivarius bacteriocin XJS01 exhibited good antibacterial activity against MDR S. aureus 2612:1606BL1486 (henceforth referred to as S. aureus_26), but its molecular mechanism remains unknown. Herein, we investigated the antibacterial mechanism of XJS01 on S. aureus_26 using an approach combining transcriptomics and metabolomics. The results showed that XJS01 induced significant changes at both transcriptional and metabolic levels in S. aureus_26. In total, 231 differentially expressed genes (DEGs) and 206 differentially abundance metabolites (DAMs) were identified in S. aureus_26 treated with 1 × MIC (minimum inhibition concentration) XJS01 compared with untreated (XJS01-free) cells (control). Functional analysis revealed that these DEGs and DAMs, alone with the related pathways and biological processes, were typically involved in stress response, being primarily related to metal uptake, cell virulence, self-help mechanism, amino acid and energy metabolism, bacterial stress response (e.g., two-component system), and membrane transport (e.g., phosphotransferase system). Overall, this study uncovered the multi-target effects of bacteriocins against MDR S. aureus at the genome-wide transcriptional and metabolic levels. These findings might be useful in the development of bacteriocins for the control of MDR S. aureus and other drug-resistant bacteria.
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Bacteriocinas , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Bacteriocinas/genética , Bacteriocinas/metabolismo , Bacteriocinas/farmacologia , Staphylococcus aureus , Staphylococcus aureus Resistente à Meticilina/genética , Antibacterianos/química , Bactérias/metabolismo , Testes de Sensibilidade Microbiana , Perfilação da Expressão GênicaRESUMO
Expression quantitative trait locus (eQTL) analysis is a powerful tool used to investigate genetic variations in complex diseases, including cancer. We previously developed a comprehensive database, PancanQTL, to characterize cancer eQTLs using The Cancer Genome Atlas (TCGA) dataset, and linked eQTLs with patient survival and GWAS risk variants. Here, we present an updated version, PancanQTLv2.0 (https://hanlaboratory.com/PancanQTLv2/), with advancements in fine-mapping causal variants for eQTLs, updating eQTLs overlapping with GWAS linkage disequilibrium regions and identifying eQTLs associated with drug response and immune infiltration. Through fine-mapping analysis, we identified 58 747 fine-mapped eQTLs credible sets, providing mechanic insights of gene regulation in cancer. We further integrated the latest GWAS Catalog and identified a total of 84 592 135 linkage associations between eQTLs and the existing GWAS loci, which represents a remarkable â¼50-fold increase compared to the previous version. Additionally, PancanQTLv2.0 uncovered 659516 associations between eQTLs and drug response and identified 146948 associations between eQTLs and immune cell abundance, providing potentially clinical utility of eQTLs in cancer therapy. PancanQTLv2.0 expanded the resources available for investigating gene expression regulation in human cancers, leading to advancements in cancer research and precision oncology.
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Bases de Dados Genéticas , Neoplasias , Locos de Características Quantitativas , Humanos , Regulação da Expressão Gênica , Estudo de Associação Genômica Ampla , Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Medicina de Precisão , Locos de Características Quantitativas/genéticaRESUMO
Proteolysis-targeting chimera (PROTAC) and other targeted protein degradation (TPD) molecules that induce degradation by the ubiquitin-proteasome system (UPS) offer new opportunities to engage targets that remain challenging to be inhibited by conventional small molecules. One fundamental element in the degradation process is the E3 ligase. However, less than 2% amongst hundreds of E3 ligases in the human genome have been engaged in current studies in the TPD field, calling for the recruiting of additional ones to further enhance the therapeutic potential of TPD. To accelerate the development of PROTACs utilizing under-explored E3 ligases, we systematically characterize E3 ligases from seven different aspects, including chemical ligandability, expression patterns, protein-protein interactions (PPI), structure availability, functional essentiality, cellular location, and PPI interface by analyzing 30 large-scale data sets. Our analysis uncovers several E3 ligases as promising extant PROTACs. In total, combining confidence score, ligandability, expression pattern, and PPI, we identified 76 E3 ligases as PROTAC-interacting candidates. We develop a user-friendly and flexible web portal ( https://hanlaboratory.com/E3Atlas/ ) aimed at assisting researchers to rapidly identify E3 ligases with promising TPD activities against specifically desired targets, facilitating the development of these therapies in cancer and beyond.
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Neoplasias , Ubiquitina-Proteína Ligases , Humanos , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Complexo de Endopeptidases do Proteassoma/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise , Ubiquitinação , Neoplasias/metabolismoRESUMO
Our previous study revealed that PI3K/AKT/mTOR signaling was associated with SCLC radioresistance. SBC2 cells were used as primary radioresistance models, while H446 cells were continuously exposed to ionizing radiation (IR) to develop acquired radioresistance. Cell viability and apoptosis assays were used to investigate synergistic effects of BEZ235/GSK2126458 and IR in vitro, while immunoblotting, metabolite quantitative analysis and bioinformatic analyses were utilized to explore the underlying mechanism. Both genetically engineered mouse models (GEMM) and subcutaneous tumor models were used to confirm the synergistic effect in vivo. Key molecules of PI3K/AKT/mTOR signaling were upregulated after IR, which was correlated with primary radioresistance, and they were more expressed in acquired radioresistant cells. BEZ235/GSK2126458 effectively enhanced the cytotoxic effects of IR. BEZ235/GSK2126458 plus IR elevated γ-H2AX and p-Nrf2 expression, suggesting DNA and oxidative stress damage were intensified. Mechanistically, BEZ235/GSK2126458 plus IR significantly reduced the expression of G6PD protein, the rate-limiting enzyme of the pentose phosphate pathway (PPP). In detail, PI3K/mTOR inhibitors reinforced interaction between G6PD and HSPA8/HSC70, and G6PD was degraded by chaperone-mediated autophagy processes. Their metabolites (NADPH and R-5P) were decreased, and ROS levels were indirectly elevated, both of which exacerbated cell death. PI3K/AKT/mTOR signaling activator, insulin, enhanced SCLC radioresistance, while the synergistic effect of BEZ235/GSK2126458 and IR can be attenuated by N-acetylcysteine, and enhanced by 6-amino niacinamide. GEMM and allograft transplantation assays further confirmed their synergistic effect in vivo. This study provided insights into the connection between PI3K/AKT/mTOR signaling and the PPP underlying radioresistance and provided evidence of mechanisms supporting PI3K/mTOR inhibitors as possible therapeutic strategies to abrogate SCLC radioresistance.
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Neoplasias Pulmonares , Quinolinas , Carcinoma de Pequenas Células do Pulmão , Animais , Camundongos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Inibidores de MTOR , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Proliferação de Células , Linhagem Celular Tumoral , Serina-Treonina Quinases TOR/metabolismo , Quinolinas/farmacologiaRESUMO
Social capital potentially affects older adults' access to healthcare services. However, the effects of social capital on the use of various types of healthcare services using longitudinal data have yet to be explored. This study aimed to examine the effects of structural and cognitive social capital on different types of healthcare utilization by older adults in Indonesia. Data were from the Indonesian Family Life Survey (waves 4 and 5) in 2007 and 2014. The sample consisted of participants aged 60 years and older who completed both waves (n = 1374). Healthcare utilization by older adults assessed health posts (posyandu), health checkups, outpatient care and hospital admissions. Social capital consisted of neighborhood trust and community participation. Generalized estimating equation models were used for the analysis. Older adults with high community participation had a higher likelihood of using preventive care in posyandu (OR = 5.848, 95% CI = 2.585-13.232) and health checkup visits (OR = 1.621, 95% CI = 1.116-2.356). Meanwhile, neighborhood trust was related to a higher probability of hospital admissions (OR = 1.255, 95% CI = 1.046-1.505). Social capital significantly affects older adults' preventive and treatment healthcare utilization. Maximizing the availability of social participation and removing barriers to access to preventive and medical care in an age-friendly environment are suggested.
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Capital Social , Humanos , Pessoa de Meia-Idade , Idoso , Indonésia , Aceitação pelo Paciente de Cuidados de Saúde , Participação da Comunidade , Participação SocialRESUMO
As omics technologies, including genomics, epigenomics, transcriptomics, T cell receptor-repertorie profiling, proteomics, metabolomics and microbiomics, have provided valuable insights into CAR T cell therapy, in our recent review, we discuss these multidimensional profiling technologies in CAR T cell research, and their potential to identify tumor-specific antigens and molecular characteristics associated with anti-tumour effects and toxicities.
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Multiômica , Neoplasias , Humanos , Imunoterapia Adotiva , Genômica/métodos , Proteômica/métodos , Epigenômica/métodos , Neoplasias/genética , Neoplasias/terapiaRESUMO
BACKGROUND: The risk factors for skin injuries remain poorly understood in cancer patients with peripherally inserted central catheters (PICC). We herein aimed at exploring the effect of clinical factors on the risk of PICC-related skin injuries. METHODS: We included 1245 cancer patients with PICC from 16 hospitals in Suzhou, China. The study outcome was in-hospital skin injuries, including contact dermatitis, skin (epidermal) stripping, tension injury, allergic dermatitis, skin tear, maceration, folliculitis, and pressure injury. RESULTS: During hospitalization, 274 patients (22.0%) developed skin injuries after prolonged use of an indwelling catheter. Univariable logistic regression analysis identified several risk factors for PICC-related skin injuries; multivariable logistic regression analysis showed that the following factors independently and significantly (p < 0.05) associated with the risk of PICC-related skin injuries: body mass index (BMI, >25 kg/m2 versus <18.5 kg/m2: odds ratio (OR), 1.79; 95% confidence interval (CI), 1.03-3.11), skin condition (humid vs normal: OR, 2.96; 95% CI, 1.62-5.43), skin indentation (OR, 4.67; 95% CI, 3.31-6.58), allergic history (OR, 2.11; 95% CI, 1.21-3.66), history of dermatitis (OR, 3.05; 95% CI, 1.00-9.28), history of eczema (OR, 3.36; 95% CI, 1.20-9.43), catheter insertion site (under elbow vs. upper arm: OR, 3.32; 95% CI, 1.12-9.90), and PICC maintenance interval (4-5 days vs ⩽3 days: OR, 0.06; 95% CI, 0.01-0.50; 5-7 days vs ⩽3 days: OR, 0.07; 95% CI, 0.02-0.31; 7-9 days vs ⩽3 days: OR, 0.10; 95% CI, 0.02-0.57). CONCLUSIONS: BMI, skin condition, skin indentation, allergic history, history of dermatitis, history of eczema, catheter insertion site, and PICC maintenance interval were independent risk factors for PICC-related skin injuries in cancer patients. This knowledge will guide future studies with formulating optimal treatment strategies for improving the skin health of cancer patients with PICC.
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Identifying predictive biomarkers of immune-related adverse events (irAEs) is crucial to maximize the benefits for patients with cancer treated with immune checkpoint inhibitors (ICIs). In a recent study published in Med,Nuñez et al. utilized multi-omics approaches and identified blood immune signatures that have the potential to predict the development of autoimmune toxicity.
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Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/etiologia , Biomarcadores , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/efeitos adversosRESUMO
Two recent studies published in Nature by Karimi et al. and Sorin et al. applied multiplexed imaging mass cytometry (IMC) to characterize the single-cell tumor immune landscapes covering millions of cells in brain tumors and lung adenocarcinomas (LUAD). They identified specific cell subtypes and cell-cell interactions that correlate with distinct clinical outcomes, thus providing valuable insights into tumor biology and prognostic prediction based on spatial architecture.
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Adenocarcinoma de Pulmão , Neoplasias Encefálicas , Neoplasias Pulmonares , Humanos , Comunicação Celular , Microambiente TumoralRESUMO
Esophageal squamous-cell carcinoma (ESCC) develops through multistage epithelial cancer formation, i.e., from normal epithelium, low- and high-grade intraepithelial neoplasia to invasive carcinoma. However, how the precancerous lesions progress to carcinoma remains elusive. Here, we report a comprehensive single-cell RNA sequencing and spatial transcriptomic study of 79 multistage esophageal lesions from 29 patients with ESCC. We reveal a gradual and significant loss of ANXA1 expression in epithelial cells due to its transcription factor KLF4 suppression along the lesion progression. We demonstrate that ANXA1 is a ligand to formyl peptide receptor type 2 (FPR2) on fibroblasts that maintain fibroblast homeostasis. Loss of ANXA1 leads to uncontrolled transformation of normal fibroblasts into cancer-associated fibroblasts (CAFs), which can be enhanced by secreted TGF-ß from malignant epithelial cells. Given the role of CAFs in cancer, our study underscores ANXA1/FPR2 signaling as an important crosstalk mechanism between epithelial cells and fibroblasts in promoting ESCC.
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Carcinoma in Situ , Neoplasias Esofágicas , Lesões Pré-Cancerosas , Humanos , Neoplasias Esofágicas/genética , Células Epiteliais , FibroblastosRESUMO
BACKGROUND: Glioblastoma (GBM) has a poor prognosis and lacks effective treatment. Anlotinib is a multitargeted receptor tyrosine kinase inhibitor (TKI) that may have anti-tumor activity in the central nervous system (CNS). This study aimed to determine the therapeutic value of radiotherapy combined with anlotinib in GBM via preclinical research. METHODS: HPLC-MS/MS was used to assess the concentration of anlotinib in blood and brain samples. Cell proliferation assays, flow cytometry, and colony formation assays were performed in vitro. The potential value of anlotinib or in combination with radiotherapy for GBM treatment was estimated in vivo. Western blotting, immunohistochemistry, and immunofluorescent staining were performed to determine the underlying mechanism. RESULTS: Anlotinib effectively inactivated the JAK3/STAT3 pathway to inhibit growth and induce apoptosis in malignant glioma cells (MGCs) independent of MGMT expression. Meanwhile, anlotinib induces MGCs G2/M arrest and sensitizes MGCs to radiation. Radiation down-regulates claudin-5 and weakens the blood-brain barrier (BBB), which contributes to the increased distribution of anlotinib in the CNS by 1.0-2.9 times. Anlotinib restrains tumor growth (PCNA), inhibits tumor microvascular proliferation (CD31), and alleviated intratumor hypoxia (HIF 1α) in vivo. Anlotinib alone or in combination with radiation is effective and safe in vivo evaluation. CONCLUSIONS: We discovered that anlotinib, the original small molecule antiangiogenesis TKI, down-regulates JAK3/STAT3 axis with anti-cancer activity alone or in combination with radiation. Anlotinib combined with radiotherapy might be a promising treatment for newly diagnosed GBM in the clinic.