Abstract
Background
We examined the prognostic significance of circulating tumor cell (CTC) dynamics during treatment in metastatic breast cancer (MBC) patients receiving first-line chemotherapy.
...Methods
Serial CTC data from 469 patients (2202 samples) were used to build a novel latent mixture model to identify groups with similar CTC trajectory (tCTC) patterns during the course of treatment. Cox regression was used to estimate hazard ratios for progression-free survival (PFS) and overall survival (OS) in groups based on baseline CTCs, combined CTC status at baseline to the end of cycle 1, and tCTC. Akaike information criterion was used to select the model that best predicted PFS and OS.
Results
Latent mixture modeling revealed 4 distinct tCTC patterns: undetectable CTCs (56.9% ), low (23.7%), intermediate (14.5%), or high (4.9%). Patients with low, intermediate, and high tCTC patterns had statistically significant inferior PFS and OS compared with those with undetectable CTCs (P < .001). Akaike Information Criterion indicated that the tCTC model best predicted PFS and OS compared with baseline CTCs and combined CTC status at baseline to the end of cycle 1 models. Validation studies in an independent cohort of 1856 MBC patients confirmed these findings. Further validation using only a single pretreatment CTC measurement confirmed prognostic performance of the tCTC model.
Conclusions
We identified 4 novel prognostic groups in MBC based on similarities in tCTC patterns during chemotherapy. Prognostic groups included patients with very poor outcome (intermediate + high CTCs, 19.4%) who could benefit from more effective treatment. Our novel prognostic classification approach may be used for fine-tuning of CTC-based risk stratification strategies to guide future prospective clinical trials in MBC.
The necessity to increase exposure in rare event search experiments by maintaining a low energy threshold and a good energy resolution leads to segmented detectors as in EDELWEISS (Dark Matter), ...CUORE (0
ν
β
β
) or Ricochet (CENNS) for example. However, the large number of sub-elements can dramatically increase the complexity of such detector arrays. In this work we report on our progress towards designing a flexible detector technology based on Kinetic Inductance Detector (KID) resonators evaporated on massive target crystals readout by a contact-less feedline. Providing that we achieve
O
(
100
)
eV energy threshold, such approach could easily be scaled to tens of kilogram detector arrays thanks to the intrinsic multiplexing capability of KIDs. Using a 30 g silicon target absorber with Al/Ti multi layers for the KID resonator, we report a significant improvement of our detector response exhibiting a keV-scale energy resolution combined with the absence of position dependence on the event location. Indeed, compared to our previous work, we are now able to properly identify calibration lines from surface (20 keV X-rays) and bulk events (60 keV gamma rays). This significant improvement is an important step towards a better understanding of phonons and quasiparticles dynamics, which is pivotal in optimizing this technology.
We report on a large-scale characterization of river discharges by employing the network framework of the horizontal visibility graph. By mapping daily time series from 141 different stations of 53 ...Brazilian rivers into complex networks, we present a useful approach for investigating the dynamics of river flows. We verified that the degree distributions of these networks were well described by exponential functions, where the characteristic exponents are almost always larger than the value obtained for random time series. The faster-than-random decay of the degree distributions is an another evidence that the fluctuation dynamics underlying the river discharges has a long-range correlated nature. We further investigated the evolution of the river discharges by tracking the values of the characteristic exponents (of the degree distribution) and the global clustering coefficients of the networks over the years. We show that the river discharges in several stations have evolved to become more or less correlated (and displaying more or less complex internal network structures) over the years, a behavior that could be related to changes in the climate system and other man-made phenomena.
•We use the horizontal visibility graph for studying river flows.•A large dataset of rivers is analyzed.•Evolutive trends are observed in the river flow dynamics.
Abstract
Background
Life course epidemiology is a powerful framework to unravel the role of socioeconomic position (SEP) disparities in hypertension (HTN). This study investigated whether life course ...SEP is associated with HTN incidence. Specifically, to test whether cumulative low SEP throughout life and unfavorable intergenerational social mobility increased HTN incidence.
METHODS
Longitudinal analysis of 8,754 ELSA-Brasil participants without HTN or cardiovascular in visit 1 (2008–2010). The response variable was the incidence of HTN between visits 1 and 2 (2012–2014). The explanatory variables were childhood, youth, and adulthood SEP, cumulative low SEP, and intergenerational social mobility. Associations were estimated by incidence rate ratios (IRRs) obtained by generalized linear models, with Poisson distribution and logarithmic link function, after adjustment for sociodemographic, behavioral, and health factors.
RESULTS
The incidence of HTN was 43.2/1,000 person-years, being higher in males, elderly (70–74 years), self-declared black, and low SEP individuals. After considering sociodemographic factors, low SEP in childhood, youth, and adulthood remained statistically associated with increased HTN incidence. Individuals in the third (IRR: 1.26; 95% confidence interval (CI): 1.11–1.44) and fourth top quartiles (IRR: 1.29; 95% CI: 1.11–1.49) of cumulative low SEP, vs. first, as well as those with low stable intergenerational trajectory (IRR: 1.29; 95% CI: 1.16–1.43), vs. high stable, also had increased HTN incidence rates.
Conclusions
Socioeconomic disparities at all phases of the life cycle appear to raise HTN incidence rates, being the individuals with greater accumulation of exposure to low SEP and with more unfavorable intergenerational mobility at greatest risk, even in a short follow-up time.
Graphical Abstract
Graphical Abstract
Adenoviral (Ad) vectors have proven to be important tools for gene and cell therapy, although some issues still need to be addressed, such as undesired interactions with blood components and ...off-target sequestration that ultimately hamper efficacy. In the past years, several organic and inorganic materials have been developed to reduce immunogenicity and improve biodistribution of Ad vectors. Here we investigated the influence of the functionalization of 14 nm PEGylated gold nanoparticles (AuNPs) with quaternary ammonium groups and an arginine-glycine-aspartic acid (RGD)-motif on the uptake and biodistribution of Ad vectors. We report the formation of Ad@AuNPs complexes that promote cell attachment and uptake, independently of the presence of the coxsackievirus and adenovirus receptor (CAR) and αvβ3 and αvβ5 integrins, significantly improving transduction without limiting Ad bioactivity. Besides, the presence of the RGD peptide favors tumor targeting and decreases Ad sequestration in the liver. Additionally, tumor delivery of a coated Ad vector expressing the human sodium iodide symporter (hNIS) by mesenchymal stem cells induces increased accumulation of radioactive iodine (131I) and tumor volume reduction compared to naked Ad-hNIS, highlighting the promising potential of our coating formulation in cancer gene therapy.
Modification of adenoviral vectors with lipids and polymers can reduce interactions with blood components and increase tumor accumulation; however, increased toxicity and reduced transduction efficiency were indicated. Coating with gold nanoparticles has proven to be a successful strategy for increasing the efficiency of transduction of receptor-defective cell lines. Here we explore the contribution of cell surface receptors on the mechanisms of entry of Ad vectors coated with gold nanoparticles in cell lines with varying degrees of resistance to infection. The enhancement of the anti-tumoral effect shown in this work provides new evidence for the potential of our formulation.
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Providing universities with high technology-enabled automation tools to support the administrative decision-making processes will enable them to achieve their objectives. For an institution to ...succeed in its everyday tasks, it should come up with the emerging and modernized management services constituted, among others, by cloud, mobile, and business analytics technology. With this, the institution’s operations and management efficiency are ensured. This study aims to develop a system with descriptive analytics named as MET Online Services that will automate and optimize the monitoring of extension services key performance indicators (KPIs) in order to help the institution in making better, data-driven decisions. The dashboards and interactive visualizations of the developed system will provide quick access to real-time progress of the extension services programs, projects, and activities. Results interpretation depicted that the developed system is indeed feasible for implementation, proven to be fully-functional and passed the quality software standards of a Certified Software Quality Assurance Specialist. As the developed system satisfied the users’ expectations and requirements, it would be an effective tool for the institution, extension services unit, and community, to make better strategic decisions and continuously deliver quality services to the community.
Tourism is one of the most prominent and rapidly expanding sectors that contribute significantly to the growth of a country’s economy. However, the tourism industry has been most adversely affected ...during the coronavirus pandemic. Thus, a reliable and accurate time series prediction of tourist arrivals is necessary in making decisions and strategies to develop the competitiveness and economic growth of the tourism industry. In this sense, this research aims to examine the predictive capability of artificial neural networks model, a popular machine learning technique, using the actual tourism statistics of the Philippines from 2008-2022. The model was trained using three distinct data compositions and was evaluated utilizing different time series evaluation metrics, to identify the factors affecting the model performance and determine its accuracy in predicting arrivals. The findings revealed that the ANN model is reliable in predicting tourist arrivals, with an R-squared value and MAPE of 0.926 and 13.9%, respectively. Furthermore, it was determined that adding training sets that contain the unexpected phenomenon, like COVID-19 pandemic, increased the prediction model's accuracy and learning process. As the technique proves it prediction accuracy, it would be a useful tool for the government, tourism stakeholders, and investors among others, to enhance strategic and investment decisions.
Water quality monitoring demands the use of spatial interpolation techniques due to on-ground challenges. The implementation of various spatial interpolation methods results in significant variations ...from the true spatial distribution of water quality in a specific location. The aim of this research is to improve mapping prediction capabilities of spatial interpolation algorithms by using a neural network with the particle swarm optimization (NN-PSO) technique. Hybrid interpolation approaches were evaluated and compared by cross-validation using mean absolute error (MAE) and Pearson’s correlation coefficient (R). The governing interpolation techniques for the physicochemical parameters of groundwater (GW) and heavy metal concentrations were the geostatistical approaches combined with NN-PSO. The best methods for physicochemical characteristics and heavy metal concentrations were observed to have the least MAE and R values, ranging from 1.7 to 4.3 times and 1.2 to 5.6 times higher than the interpolation technique without the NN-PSO for the dry and wet season, respectively. The hybrid interpolation methods exhibit an improved performance as compared to the non-hybrid methods. The application of NN-PSO technique to spatial interpolation methods was found to be a promising approach for improving the accuracy of spatial maps for GW quality.
Using Raman spectroscopy, the study of a polymorphic phase transition in the KNNLiTaLa
0.01
compound is presented. An analysis of the behavior with temperature, wavenumber and half width at full ...maximum of the individual bands, corresponding to the vibration modes of the (Nb/Ta)O
6
octahedra of the KNNLiTaLa
0.01
compound's structure, is performed. This analysis determined that the polymorphic phase transition of the KNNLiTaLa
0.01
compound occurs in the 90 to 105°C temperature interval. Using the Hard Mode Spectroscopy method, the value of the critical exponent of the order parameter was determined to be β ≈ ½, indicative of a second order transition.
We determined depth profiles of total mercury (T-Hg) in six 210Pb-dated sediment cores from Todos os Santos Bay to reconstruct the history of anthropogenic Hg accumulation. We also assessed ...superficial sediments samples from five estuaries. T-Hg concentrations (5–3500 μg kg−1) presented a large spatial and temporal variability. T-Hg concentrations in Ribeira Bay increased up to 200-fold along time, whereas the fluxes of T-Hg are substantially higher (up to 10,000 fold) than present-day wet deposition for industrialized areas. Sedimentary records indicate that a chlor-alkali plant has been the main source of Hg pollution until the present, although the T-Hg records suggest that harbor, shrimp farming, and oil refinery activities, besides Hg atmospheric depositions, are important across the bay. Sediments in the Ribeira Bay act as an important Hg sink. If sediments are eroded or disturbed, they may release Hg, thus posing a serious risk to wildlife and ecosystem health.
Sedimentary cores provide data on preindustrial levels and also anthropogenic fluxes of Hg for the appraisal of the magnitude, processes and potential risks of the contamination.
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•Sediment cores provide a reliable archive of Hg contamination during the last century.•Hg levels increased up to 200-fold following the onset of a chlor-alkali plant.•Ribeira Bay acts as important sink for the legacy Hg.•Decline of the concentrations and fluxes of Hg during the last decades•Disturbance of bottom sediments may cause remobilization and reintroduction of Hg.
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