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Background: Immune checkpoint inhibitors (ICIs) have become the mainstay treatment for non-small cell lung cancer (NSCLC). However, there is a lack of studies assessing ICIs as subsequent treatment in older adults with NSCLC and brain metastasis (BM). This retrospective cohort study compared the real-world survival of older patients with NSCLC and BM at diagnosis [synchronous BM (SBM)] previously treated with chemotherapy receiving ICI versus chemotherapy as subsequent treatment. Methods: Patients with NSCLC and SBM ≥65 years previously treated with chemotherapy were identified using the SEER-Medicare database (2010-2019). Patients receiving new chemotherapy and/or Food and Drug Administration (FDA)-approved ICIs as second/third-line treatment were included, excluding those ever-receiving targeted therapies. Each ICI patient was matched to one chemotherapy patient by time to subsequent treatment (within ±30 days) from diagnosis. Overall survival (OS) time was measured from the start of subsequent treatment to death, censored at disenrollment from Medicare Part A/B, enrollment in Part C, or end of study (December 31, 2019), whichever came first. OS curves were estimated and compared using the Kaplan-Meier (KM) method and log-rank test. Hazard ratio (HR) was estimated using a multivariable-adjusted Cox proportional hazards model. Results: Matched cohorts included 546 patients [273 in each group; median age 71 (range, 65-87) years]. ICI patients were older, more likely non-Hispanic, with squamous cell carcinoma, and liver metastasis compared to chemotherapy. KM estimated better survival in ICI than chemotherapy {median survival: 209 days [95% confidence interval (CI): 160-275] vs. 155 days (95% CI: 135-187); log-rank P<0.001}. ICI was associated with a lower adjusted hazard of death [HR =0.63; 95% CI: 0.52-0.75; P<0.001] compared to subsequent chemotherapy treatment. Conclusions: In this population-based study of older patients with NSCLC and SBM previously treated with chemotherapy, subsequent treatment with ICI was associated with improved survival compared to chemotherapy.
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BACKGROUND: Circular RNAs play an important role in the development of gastric cancer (GC). circ-LDLRAD3 has been confirmed to be related to GC progression. miR-137 is also a suppressor in GC. However, the impact of the interaction between circ-LDLRAD3 and miR-137 on the progression of gastric cancer remains unclear at present. METHODS: The study identified expression level differences of circ-LDLRAD3, miR-137, and COL4A5 in gastric cancer pathological specimens compared to normal tissue samples. Furthermore, through in vitro experiments, including flow cytometry, CCK-8 assays, wound healing, Western blotting, and colony formation assays, we further explored the molecular regulatory mechanisms by which these factors promote the progression of gastric cancer. RESULTS: In this study, circ-LDLRAD3 was confirmed to have higher expression, and miR-137 had lower expression in GC tissues and cell lines. circ-LDLRAD3 knockdown and miR-137 overexpression promoted apoptosis and inhibited proliferation, migration and invasion in GC cell lines. Further experiments validated that COL4A5 has a positive relationship with GC and that circ-LDLRAD3 promotes the expression of COL4A5. circ-LDLRAD3 could be sponged and inhibited by miR-137 in GC cells. As a result, the promotional effect of circ-LDLRAD3 on COL4A5 is counteracted by miR-137. CONCLUSION: In conclusion, we found that the knockdown of circ-LDLRAD3 suppressed the development of GC by regulating the miR-137/COL4A5 axis.
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INTRODUCTION/BACKGROUND: To assess racial/ethnic disparities in endocrine therapy (ET) adherence among women with breast cancer. MATERIALS AND METHODS: A retrospective cohort study of Arkansas All-Payer Claims Database (APCD) linked to Arkansas Cancer Registry (ACR). Women with stages 0-3 HR+ breast cancer diagnosed in 2013-2017 were followed from cancer diagnosis for a year to determine ET initiation. Among women who initiated ETs within 1 year of diagnosis, we assessed first-year compliance (proportion of days covered ≥ 0.8) and followed them for 5 years, censoring at death, end of data availability (December 21, 2019), or disenrollment from insurance coverage, whichever occurred first, to determine time to discontinuation. Regression analysis was conducted to determine racial/ethnic disparities in ET use adjusting for patients demographic, clinical, tumor characteristics and county-level socioeconomic factors. RESULTS: Among women with continuous insurance coverage, 81% initiated ET within 1 year of diagnosis; 80% were compliant in the first year of ET use and 27.4% discontinued ET by year 5 among those who initiated ET in the first year. There were no racial/ethnic differences in ET initiation or first-year compliance adjusting for covariates. NHB women were significantly less likely to discontinue ET within 5 years after ET initiation compared to NHW women after (HR, 95% CI, 0.76, 0.58-0.98; P = .035). CONCLUSION: After adjusting for patients' and tumor characteristics, there were no racial/ethnic differences in ET initiation within 1 year of diagnosis and ET compliance within first year of ET use. However, NHB women were less likely to discontinue ET within 5 years of initiation.
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In this study, the goal was to develop a method for detecting and classifying organophosphorus pesticides (OPPs) in bodies of water. Sixty-five samples with different concentrations were prepared for each of the organophosphorus pesticides, namely chlorpyrifos, acephate, parathion-methyl, trichlorphon, dichlorvos, profenofos, malathion, dimethoate, fenthion, and phoxim, respectively. Firstly, the spectral data of all the samples was obtained using a UV-visible spectrometer. Secondly, five preprocessing methods, six manifold learning methods, and five machine learning algorithms were utilized to build detection models for identifying OPPs in water bodies. The findings indicate that the accuracy of machine learning models trained on data preprocessed using convolutional smoothing + first-order derivatives (SG + FD) outperforms that of models trained on data preprocessed using other methods. The backpropagation neural network (BPNN) model exhibited the highest accuracy rate at 99.95%, followed by the support vector machine (SVM) and convolutional neural network (CNN) models, both at 99.92%. The extreme learning machine (ELM) and K-nearest neighbors (KNN) models demonstrated accuracy rates of 99.84% and 99.81%, respectively. Following the application of a manifold learning algorithm to the full-wavelength data set for the purpose of dimensionality reduction, the data was then visualized in the first three dimensions. The results demonstrate that the t-distributed domain embedding (t-SNE) algorithm is superior, exhibiting dense clustering of similar clusters and clear classification of dissimilar ones. SG + FD-t-SNE-SVM ranks highest among the feature extraction models in terms of performance. The feature extraction dimension was set to 4, and the average classification accuracy was 99.98%, which slightly improved the prediction performance over the full-wavelength model. As shown in this study, the ultraviolet-visible (UV-visible) spectroscopy system combined with the t-SNE and SVM algorithms can effectively identify and classify OPPs in waterbodies.
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Redes Neurales de la Computación , Compuestos Organofosforados , Plaguicidas , Contaminantes Químicos del Agua , Plaguicidas/análisis , Contaminantes Químicos del Agua/análisis , Aprendizaje Automático , Máquina de Vectores de Soporte , Monitoreo del Ambiente/métodos , Algoritmos , Agua/químicaRESUMEN
Canine circovirus (CanineCV) is a recently identified member of the Circoviridae family. Since its discovery in 2011, CanineCV has been detected in different countries worldwide, infecting both domestic and wild canids. The virus is potentially associated with gastrointestinal and respiratory illnesses. In 2016, CanineCV was reported in the southwestern region of Guangxi, China. However, its prevalence in other provinces in the Southwest region remained unknown. This study collected a total of 208 serum samples from domestic dogs in Sichuan, China in 2022 to investigate the prevalence of CanineCV. Among these samples, 26 tested positive for CanineCV, resulting in a positivity rate of 12.5%. Additionally, 12 strains were sequenced, 9 of which had a sequence length of 2,063 nucleotides (nt), 2 of the other threes had a length of 2,062 nts and another was 2,064 nt. Notably, a frameshift mutation was identified, resulting in a truncated ORF1 and the occurrence of a novel sequence comprised of 13 amino acids at the end of the replicate protein (Rep). This mutation could affect the replication cycle of the virus. Phylogenetic and evolutionary analyses revealed that the isolates belonged to the CanineCV-3 genotype and were prevalent in the Southeast and the Southwest regions of China, as well as in the neighboring countries alongside other strains of the same genotype. Collectively, this epidemiological investigation widens our understanding of the genetic diversity of CanineCV in Southwest China and provides insights into viral evolution.
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OBJECTIVES: To evaluate the quality of Arkansas All-Payer Claims Database (APCD) for disparity research in persistent poverty areas by determining (1) its representativeness of Arkansas population, (2) variation by county, and (3) differences in coverage between persistent poverty and other counties. DATA SOURCES: Cross-sectional study using 2019 Arkansas APCD member enrollment data and county-level data from various agencies. DATA COLLECTION/EXTRACTION METHODS: An alias identifier linked persons across insurance plans. County FIPS codes were used to extract county-level variables. STUDY DESIGN: Cohort 1 included individuals with ≥1 day of medical coverage in 2019. Cohort 2 included individuals with medical coverage in June, 2019. Cohort 3 included individuals with continuous medical coverage in 2019. Sampling proportions of a county's population in the three cohorts were compared between persistent poverty and other counties. Inverse-variance weighted linear regression was used to identify county-level socioeconomic and demographic characteristics associated with inclusion in each cohort. PRINCIPAL FINDINGS: In 2019, 73.6% of Arkansans had medical coverage for ≥1 day (Cohort 1), 66.3% had coverage in June (Cohort 2), and 58.8% had continuous coverage (Cohort 3) in APCD. Sampling proportions varied by county (median[range]: Cohort 1, 78% [58%-95%]; Cohort 2, 71% [51%-88%]; and Cohort 3, 64% [44%-80%]), and were higher among persistent poverty counties than others for all three cohorts (mean [SD], persistent poverty vs. other: Cohort 1: 80.9% [6.4%] vs. 77.1% [6.3%], p = 0.04; Cohort 2: 74.0% [6.4%] vs. 70.1% [6.2%], p = 0.03; Cohort 3: 66.4% [6.1%] vs. 62.7% [6.0%], p = 0.03). In the 2019 APCD, larger counties and those with higher proportions of females or persons 65+ years had higher coverage, whereas counties with higher per capita household income, median home value, or disproportionately more persons of other races (non-White and non-Black) had lower coverage (p < 0.05 for all three cohorts). CONCLUSIONS: The Arkansas APCD had good coverage of Arkansas population. Coverage was higher in persistent poverty counties than others.
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Pobreza , Humanos , Arkansas , Estudios Transversales , Femenino , Masculino , Persona de Mediana Edad , Adulto , Pobreza/estadística & datos numéricos , Anciano , Adolescente , Bases de Datos Factuales , Adulto Joven , Preescolar , Cobertura del Seguro/estadística & datos numéricos , Factores Socioeconómicos , Niño , Revisión de Utilización de Seguros/estadística & datos numéricos , Lactante , Seguro de Salud/estadística & datos numéricos , Áreas de PobrezaRESUMEN
Pulmonary hypertension (PH) is a fatal disease with no existing curative drugs. NF-E2-related factor 2 (NRF2) a pivotal molecular in cellular protection, was investigated in PH models to elucidate its role in regulating abnormal phenotypes in pulmonary artery cells. We examined the expression of NRF2 in PH models and explored the role of NRF2 in regulating abnormal phenotypes in pulmonary artery cells. We determined the expression level of NRF2 in lung tissues of PH model decreased significantly. We found that NRF2 was reduced in rat pulmonary artery endothelial cells (rPAEC) under hypoxia, while it was overexpressed in rat pulmonary artery smooth muscle cells (rPASMC) under hypoxia. Next, the results showed that knockdown NRF2 in rPAEC promoted endothelial-mesenchymal transformation and upregulated reactive oxygen species level. After the rPASMC was treated with siRNA or activator, we found that NRF2 could accelerate cell migration by affecting MMP2/3/7, and promote cell proliferation by regulating PDGFR/ERK1/2 and mTOR/P70S6K pathways. Therefore, the study has shown that the clinical application of NRF2 activator in the treatment of pulmonary hypertension may cause side effects of promoting the proliferation and migration of rPASMC. Attention should be paid to the combination of NRF2 activators.
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Movimiento Celular , Proliferación Celular , Hipertensión Pulmonar , Factor 2 Relacionado con NF-E2 , Arteria Pulmonar , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Animales , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/genética , Hipertensión Pulmonar/patología , Ratas , Arteria Pulmonar/metabolismo , Arteria Pulmonar/patología , Miocitos del Músculo Liso/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Células Endoteliales/metabolismo , Masculino , Transducción de Señal , Transición Epitelial-Mesenquimal/genética , Ratas Sprague-Dawley , Modelos Animales de EnfermedadRESUMEN
To observe the antitumour efficacy of programmed death 1 (PD-1) inhibitors in the real world and explore the relationship between NRS2002 score or other clinical characteristics and immunotherapy efficacy, we retrospectively analyzed 341 tumor patients who received immune checkpoint inhibitor (ICI) treatment at one center. A total of 341 solid tumor patients treated with ICIs from June 2018 to December 2021 were retrospectively included in this study. Patient characteristics, ICI responses, and survival status were documented, and the relationships between clinical factors and survival were analyzed. Among all patients, the median progression-free survival (PFS) was 5.8 months, and the median overall survival (OS) was 12.5 months. The Performance Status (PS), NRS2002 score, The Naples Prognostic Score (NPS), Lymphocyte and C-reactive protein ratio (LCR), line of therapy, and nutritional support were significantly related to PFS or OS according to univariate analysis. The median PFS and OS were significantly better in the group without nutritional risk (NRS2002 0-2) than those with nutritional risk (NRS2002 ≥ 3) (PFS: HR = 1.82, 95% CI 1.30-2.54, p value < .001; OS: HR = 2.49, 95% CI 1.73-3.59, p value < .001). Cox regression analysis revealed that the NRS2002 score was an independent prognostic factor for both PFS and OS. The objective response rate (ORR) in the group at nutritional risk was lower than that in the group without nutritional risk (8.33% and 19.71%, respectively, p value = .037). Patients at nutritional risk according to the NRS2002 score at initial treatment had a poorer prognosis than those without nutritional risk. The NRS2002 could be used as a preliminary index to predict the efficacy of immune checkpoint inhibitor therapy.
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Inhibidores de Puntos de Control Inmunológico , Neoplasias , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacología , Masculino , Femenino , Neoplasias/tratamiento farmacológico , Neoplasias/mortalidad , Pronóstico , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Adulto , Anciano de 80 o más Años , Supervivencia sin ProgresiónRESUMEN
Background: The Chikungunya virus is an Alphavirus that belongs to the Togaviridae family and is primarily transmitted by mosquitoes. It causes acute infection characterized by fever, headache, and arthralgia. Some patients also experience persistent chronic osteoarthritis-like symptoms. Dedicated antiviral treatments are currently unavailable for CHIKV. This study aims to explore the potential anti-CHIKV effect of rosmarinic acid using network pharmacology. Methods: This study employed network pharmacology to predict and verify the molecular targets and pathways associated with ROSA in the context of CHIKV. The analysis outcomes were further validated using molecular docking and in vitro experiments. Results: The analysis of CHIKV targets using the Kyoto Encyclopedia of Genes and Genomes and MCODE identified IL-17 as an important pathogenic pathway in CHIKV infection. Among the 30 targets of ROSA against CHIKV, nearly half were found to be involved in the IL-17 signaling pathway. This suggests that ROSA may help the host in resisting CHIKV invasion by modulating this pathway. Molecular docking validation results showed that ROSA can stably bind to 10 core targets out of the 30 identified targets. In an in vitro CHIKV infection model developed using 293T cells, treatment with 60 µM ROSA significantly improved the survival rate of infected cells, inhibited 50% CHIKV proliferation after CHIKV infection, and reduced the expression of TNF-α in the IL-17 signaling pathway. Conclusion: This study provides the first confirmation of the efficacy of ROSA in suppressing CHIKV infection through the IL-17 signaling pathway. The findings warrant further investigation to facilitate the development of ROSA as a potential treatment for CHIKV infection.
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Antivirales , Fiebre Chikungunya , Virus Chikungunya , Cinamatos , Depsidos , Interleucina-17 , Simulación del Acoplamiento Molecular , Ácido Rosmarínico , Transducción de Señal , Depsidos/farmacología , Cinamatos/farmacología , Virus Chikungunya/efectos de los fármacos , Interleucina-17/metabolismo , Humanos , Antivirales/farmacología , Transducción de Señal/efectos de los fármacos , Fiebre Chikungunya/tratamiento farmacológico , Fiebre Chikungunya/virología , Farmacología en Red , Células HEK293 , Replicación Viral/efectos de los fármacos , AnimalesRESUMEN
Interferon regulatory factor (IRF) family genes play a critical role in colorectal cancer (CRC) development and impact patient survival. This study evaluated the influence of functional single nucleotide polymorphisms (SNPs) in IRF genes on CRC survival, including functional predictions and experimental validations. Multivariate Cox regression analysis identified three linked SNPs as significant survival predictors, with the rs141112353 T/T genotype in the 3'UTR region of IRF6 significantly associated with decreased survival (HR = 1.60, P = 6E-04). Expression quantitative trait loci (eQTL) analysis indicated that the rs141112353 TA > T alteration reduced IRF6 expression. Dual luciferase assays showed lower activity for the T allele in the presence of hsa-miR-548ap-3p. Data from The Cancer Genome Atlas (TCGA) and other databases confirmed lower IRF6 levels in CRC tissues, correlating with worse survival and inversely with M2 macrophage infiltration. In vitro, IRF6 overexpression inhibited CRC cell proliferation and M2 macrophage polarization by downregulating MIF expression. These findings suggest that the IRF6 rs141112353 TA > T variant significantly affects CRC survival, potentially by enhancing miR-548-ap-3p binding affinity.
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Neoplasias Colorrectales , Regulación Neoplásica de la Expresión Génica , Factores Reguladores del Interferón , Polimorfismo de Nucleótido Simple , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Factores Reguladores del Interferón/genética , Sitios de Carácter Cuantitativo , MicroARNs/genética , Femenino , Masculino , Proliferación Celular/genética , Pronóstico , Línea Celular Tumoral , Regiones no Traducidas 3' , Persona de Mediana Edad , Macrófagos/metabolismoRESUMEN
Chiral multi-resonance thermally activated delayed fluorescence (CP-MR-TADF) materials hold promise for circularly polarized organic light-emitting diodes (CP-OLEDs) and 3D displays. Herein, we present two pairs of tetraborated intrinsically axial CP-MR-TADF materials, R/S-BDBF-BOH and R/S-BDBT-BOH, with conjugation-extended bidibenzo[b,d]furan and bidibenzo[b,d]thiophene as chiral sources, which effectively participate in the distribution of the frontier molecular orbitals. Due to the heavy-atom effect, sulfur atoms are introduced to accelerate the reverse intersystem crossing process and increase the efficiency of molecules. R/S-BDBF-BOH and R/S-BDBT-BOH manifest ultra-pure blue emission with a maximum at 458/459â nm with a full width at half maximum of 27â nm, photoluminescence quantum yields of 90 %/91 %, and dissymmetry factors (|gPL|) of 6.8×10-4/8.5×10-4, respectively. Correspondingly, the CP-OLEDs exhibit good performances with an external quantum efficiency of 30.1 % and |gEL| factors of 1.2×10-3.
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The development of intelligent, sensitive, and visual methods for the rapid detection of veterinary drug residues is essential to ensure food quality and safety. Here, a smartphone-based dual inverse signal MOFs fluorescence sensing system was proposed for intelligent in-site visual detection of malachite green (MG). A UiO-66-NH2@RhB-dual-emission fluorescent probe was successfully synthesized in one step using a simple one-pot method. The inner filter effect (IFE) quenches the red fluorescence, while hydrogen bonding interaction enhances the blue fluorescence, enabling highly sensitive, accurate, and visual detection of MG dual inverse signals through fluorescence analysis. The probe showed great linearity over a wide range of 0.1-100 µmol/L, with a limit of detection (LOD) of 20 nmol/L. By integrating smartphone photography and RGB (red, green, and blue) analysis, accurate quantitative analysis of MG in water and actual fish samples can be achieved within 5 min. This developed platform holds great promise for the on-site detection of MG in practical applications, with the advantages of simplicity, cost-effectiveness, and rapidity. Consequently, it may open up a new pathway for on-site evaluation of food safety and environmental health.
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Colorantes Fluorescentes , Colorantes de Rosanilina , Teléfono Inteligente , Colorantes de Rosanilina/análisis , Colorantes de Rosanilina/química , Colorantes Fluorescentes/química , Espectrometría de Fluorescencia/métodos , Animales , Límite de Detección , Fluorescencia , Peces , Contaminantes Químicos del Agua/análisisRESUMEN
Uranium plays a pivotal role in the nuclear industry; however, its inadvertent release has raised concerns regarding health and environmental implications. It is crucial for a prompt warning and accurate tracing of uranium contamination in emergency scenarios. In this study, a novel and simple method was proposed that combines magnetic dispersive solid-phase extraction (MDSPE) with portable X-ray fluorescence spectrometry (XRF) for the on-site sampling and determination of trace uranium in real samples. A magnetic covalent organic framework (Fe3O4@COF) composite with excellent chemical stability and a large adsorption capacity of 311 mg/g was synthesized and employed as an efficient adsorbent for the solid-phase extraction of trace uranium. Without the need for a centrifuge or filter requirement, the established method by benchtop wavelength-dispersive X-ray fluorescence spectrometry (WDXRF) exhibits an exceptionally low limit of detection (LOD) of 0.008 µg/L with a sample volume of 50 mL and a fast adsorption time of 15 min, rendering it suitable for environmental monitoring of UO22+. Consequently, this approach, in combination with a hand-held portable XRF instrument with an LOD of 0.1 µg/L, was successfully implemented for the on-site extraction and quality assessment of real water samples, yielding accurate results and satisfactory spike recoveries.
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INTRODUCTION: This study aimed to evaluate the association of race/ethnicity and patient care experiences (PCEs) with healthcare utilization and costs among US older adults with prostate cancer (PCa). MATERIALS AND METHODS: The study used data from 2007 to 2015 Surveillance, Epidemiology, and End Results dataset linked to Medicare Consumer Assessment of Healthcare Providers and Systems survey and Medicare claims (SEER-CAHPS). We identified males aged ≥65 years who completed a CAHPS survey within 6-60 months post-PCa diagnosis. Covariate-adjusted associations of six CAHPS PCE composite measures with any emergency department visit and any inpatient stay (using logistic regressions), and with total part A and part B Medicare costs (using generalized linear models) were examined by race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, non-Hispanic Asian, and other). RESULTS: Among 1834 PCa survivors, a 1-point higher score for getting care quickly was associated with higher odds (odds ratio 1.08; 95% confidence interval [CI]: 1.02-1.15; p = 0.009) of any inpatient stay in Hispanic patients. Higher total costs were associated with a 1-point higher score for getting needed care among Hispanic patients ($590.84; 95% CI: $262.15, $919.53; p < 0.001); a 1-point higher score for getting care quickly among Hispanic patients ($405.26; 95% CI: $215.83, $594.69; p < 0.001); and a 1-point higher score for customer service among patients belonging to other races ($361.69; 95% CI: $15.68, $707.69; p = 0.04). DISCUSSION: We observed differential associations by race/ethnicity between PCEs and healthcare utilization and costs. Further research is needed to explore the causes of these associations.
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Supervivientes de Cáncer , Neoplasias de la Próstata , Masculino , Humanos , Anciano , Estados Unidos , Etnicidad , Medicare , Próstata , Programa de VERF , Neoplasias de la Próstata/terapia , Atención al Paciente , Costos de la Atención en Salud , Aceptación de la Atención de SaludRESUMEN
Polymer materials formed by conventional metal-ligand bonds have very low branch functionality, the crosslinker of such polymer usually consists of 2-4 polymer chains and a single metal ion. Thus, these materials are weak, soft, humidity-sensitive, and unable to withstand their shape under long-term service. In this work, a new hyperbranched metal-organic cluster (MOC) crosslinker containing up to 16 vinyl groups is prepared by a straightforward coordination reaction. Compared with the current typical synthesis of metal-organic cages (MOCs) or metal-organic-polyhedra (MOP) crosslinkers with complex operations and low yield, the preparation of the MOC is simple and gram-scale. Thus, MOC can serve as a high-connectivity crosslinker to construct hyper-crosslinked polymer networks. The as-prepared elastomer exhibits mechanical robustness, creep-resistance, and humidity-stability. Besides, the elastomer possesses self-healing and recyclability at mild condition as well as fluorescence stability. These impressive comprehensive properties are proven to originate from the hyper-crosslinked topological structure and microphase-separated morphology. The MOC-driven hyper-crosslinked elastomers provide a new solution for the construction of mechanically robust, durable, and multifunctional polymers.
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Designing materials capable of adapting their mechanical properties in response to external stimuli is the key to preventing failure and extending their service life. However, existing mechanically adaptive polymers are hindered by limitations such as inadequate load-bearing capacity, difficulty in achieving reversible changes, high cost, and a lack of multiple responsiveness. Herein, we address these challenges using dynamic coordination bonds. A new type of mechanically adaptive material with both rate- and temperature-responsiveness was developed. Owing to the stimuli-responsiveness of the coordination equilibria, the prepared polymers, PBMBD-Fe and PBMBD-Co, exhibit mechanically adaptive properties, including temperature-sensitive strength modulation and rate-dependent impact hardening. Benefitting from the dynamic nature of the coordination bonds, the polymers exhibited impressive energy dissipation, damping capacity (loss factors of 1.15 and 2.09 at 1.0â Hz), self-healing, and 3D printing abilities, offering durable and customizable impact resistance and protective performance. The development of impact-resistant materials with comprehensive properties has potential applications in the sustainable and intelligent protection fields.
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Compared with traditional piezoelectric ultrasonic devices, optoacoustic devices have unique advantages such as a simple preparation process, anti-electromagnetic interference, and wireless long-distance power supply. However, current optoacoustic devices remain limited due to a low damage threshold and energy conversion efficiency, which seriously hinder their widespread applications. In this study, using a self-healing polydimethylsiloxane (PDMS, Fe-Hpdca-PDMS) and carbon nanotube composite, a flexible optoacoustic patch is developed, which possesses the self-healing capability at room temperature, and can even recover from damage induced by cutting or laser irradiation. Moreover, this patch can generate high-intensity ultrasound (> 25 MPa) without the focusing structure. The laser damage threshold is greater than 183.44 mJ cm-2, and the optoacoustic energy conversion efficiency reaches a major achievement at 10.66 × 10-3, compared with other carbon-based nanomaterials and PDMS composites. This patch is also been successfully examined in the application of acoustic flow, thrombolysis, and wireless energy harvesting. All findings in this study provides new insight into designing and fabricating of novel ultrasound devices for biomedical applications.
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OBJECTIVE: This study compared opioid utilization trajectories of persons initiating tramadol, short-acting hydrocodone, or short-acting oxycodone, and it characterized opioid dose trajectories and type of opioid in persistent opioid therapy subsamples. METHODS: A retrospective cohort study of adults with chronic non-cancer pain who were initiating opioid therapy was conducted with the IQVIA PharMetrics® Plus for Academics data (2008-2018). Continuous enrollment was required for 6 months before ("baseline") and 12 months after ("follow-up") the first opioid prescription ("index date"). Opioid therapy measures were assessed every 7 days over follow-up. Group-based trajectory modeling (GBTM) was used to identify trajectories for any opioid and total morphine milligram equivalent measures, and longitudinal latent class analysis was used for opioid therapy type. RESULTS: A total of 40 276 tramadol, 141 023 hydrocodone, and 45 221 oxycodone initiators were included. GBTM on any opioid therapy identified 3 latent trajectories: early discontinuers (tramadol 39.0%, hydrocodone 54.1%, oxycodone 61.4%), late discontinuers (tramadol 37.9%, hydrocodone 39.4%, oxycodone 33.3%), and persistent therapy (tramadol 6.7%, hydrocodone 6.5%, oxycodone 5.3%). An additional fourth trajectory, intermittent therapy (tramadol 16.4%), was identified for tramadol initiators. Of those on persistent therapy, 2687 individuals were on persistent therapy with tramadol, 9169 with hydrocodone, and 2377 with oxycodone. GBTM on opioid dose resulted in 6 similar trajectory groups in each persistent therapy group. Longitudinal latent class analysis on opioid therapy type identified 6 latent classes for tramadol and oxycodone and 7 classes for hydrocodone. CONCLUSION: Opioid therapy patterns meaningfully differed by the initial opioid prescribed, notably the presence of intermittent therapy among tramadol initiators and higher morphine milligram equivalents and prescribing of long-acting opioids among oxycodone initiators.
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Dolor Crónico , Tramadol , Adulto , Humanos , Analgésicos Opioides/uso terapéutico , Tramadol/uso terapéutico , Oxicodona/uso terapéutico , Hidrocodona/uso terapéutico , Estudios de Seguimiento , Estudios Retrospectivos , Dolor Crónico/tratamiento farmacológicoRESUMEN
PURPOSE: This study aimed to evaluate the association of race/ethnicity, patient care experiences (PCEs), and receipt of definitive treatment and treatment modality among older adults in the United States (US) with localized prostate cancer (PCa). METHODS: Using Surveillance, Epidemiology and End Results dataset linked to Medicare Consumer Assessment of Healthcare Providers and Systems (SEER-CAHPS) for 2007-2015, we identified men aged ≥ 65 years who completed a CAHPS survey within one year before and one year after PCa diagnosis. Associations of race/ethnicity (non-Hispanic White (NHW), non-Hispanic Black (NHB), Hispanic, non-Hispanic Asian (NHA), and other) and of interactions between race/ethnicity and PCEs (getting needed care, getting care quickly, doctor communication, and care coordination) with the receipt of definitive PCa treatment and treatment modality within 3 and 6 months of diagnosis were examined using logistic regressions. RESULTS: Among 1,438 PCa survivors, no racial/ethnic disparities in the receipt of definitive treatment were identified. However, NHB patients were less likely to receive surgery (vs. radiation) within 3 and 6 months of PCa diagnosis than NHW patients (OR 0.397, p = 0.006 and OR 0.419, p = 0.005), respectively. Among NHA patients, a 1-point higher score for getting care quickly was associated with lower odds (OR 0.981, p = 0.043) of receiving definitive treatment within 3 months of PCa diagnosis, whereas among NHB patients, a 1-point higher score for doctor communication was associated with higher odds (OR 1.023, p = 0.039) of receiving definitive treatment within 6 months of PCa diagnosis. DISCUSSION: We observed differential associations between PCEs and receipt of definitive treatment based on patient race/ethnicity. Further research is needed to explore these associations.
Asunto(s)
Supervivientes de Cáncer , Neoplasias de la Próstata , Masculino , Humanos , Anciano , Estados Unidos/epidemiología , Etnicidad , Medicare , Próstata , Programa de VERF , Neoplasias de la Próstata/epidemiología , Atención al PacienteRESUMEN
PURPOSE: Over the years, animal models of local heart irradiation have provided insight into mechanisms of and treatments for radiation-induced heart disease in human populations. However, it is not completely clear which manifestations of radiation injury are most commonly seen after whole heart irradiation, and whether certain biological factors impact experimental results. Combining 9 homogeneous studies in rat models of whole heart irradiation from one laboratory, we sought to identify experimental and/or biological factors that impact heart outcomes. We evaluated the usefulness of including (1) heart rate and (2) bodyweight as covariates when analyzing biological parameters, and (3) we determined which echocardiography, histological, and immunohistochemistry parameters are most susceptible to radiation effects. Finally, (4) as an educational example, we illustrate a hypothetical sample size calculation for a study design commonly used in evaluating radiation modifiers, using the pooled estimates from the 9 rat studies only for context. The results may assist investigators in the design and analyses of pre-clinical studies of whole heart irradiation. MATERIALS AND METHODS: We made use of data from 9 rat studies from our labs, 8 published elsewhere in 2008-2017, and one unpublished study. Echocardiography, histological, and immunohistochemical parameters were collected from these studies. Using mixed effects analysis of covariance models, we estimated slopes for heart rate and bodyweight and estimated the radiation effect on each of the parameters. RESULTS: Bodyweight was related to most echocardiography parameters, and heart rate had an effect on echocardiography parameters related to the diameter of the left ventricle. For some parameters, there was evidence that heart rate and bodyweight relationships with the parameter depended on whether the rats were irradiated. Radiation effects were found in systolic measures of echocardiography parameters related to the diameter of the left ventricle, with ejection fraction and fractional shortening, with atrial wall thickness, and with histological measures of capillary density, collagen deposition, and mast cells infiltration in the heart. CONCLUSION: Accounting for bodyweight, as well as heart rate, in analyses of echocardiography parameters should reduce variability in estimated radiation effects. Several echocardiography and histological parameters were particularly susceptible to whole heart irradiation, showing robust effects compared to sham-irradiation. Lastly, we provide an example approach for a sample size calculation that will contribute to a rigorous study design and reproducibility in experiments studying radiation modifiers.