In this article, an innovative approach to microwave imaging, which combines a qualitative imaging technique and deep learning (DL), is presented. The goal is to develop a tool for reliable and ...user-independent retrieval of the shape of unknown targets from the knowledge of the scattered fields. Qualitative imaging methods are powerful inverse scattering tools, as they provide morphological information in real time. However, their outcome is a continuous map, which has to be hard-thresholded to clearly identify the targets. This thresholding unavoidably results in case-dependent, often user-biased, results. To deal with this issue, a DL approach, based on a physics-assisted deep neural network, is proposed to automatically classify image pixels, i.e., to generate binary masks, separating the targets (foreground) from the background. In particular, the proposed network binarizes the output of a qualitative imaging inversion technique known as the orthogonality sampling method. For the sake of comparison, a DL method is also exploited, which generates the binary masks directly from the scattered fields without any qualitative imaging aid. A quantitative assessment of the performances of both methods and a test on experimental data are provided.
Microwave imaging is emerging as an alternative modality to conventional medical diagnostics technologies. However, its adoption is hindered by the intrinsic difficulties faced in the solution of the ...underlying inverse scattering problem, namely non-linearity and ill-posedness. In this paper, an innovative approach for a reliable and automated solution of the inverse scattering problem is presented, which combines a qualitative imaging technique and deep learning in a two-step framework. In the first step, the orthogonality sampling method is employed to process measurements of the scattered field into an image, which explicitly provides an estimate of the targets shapes and implicitly encodes information in their contrast values. In the second step, the images obtained in the previous step are fed into a neural network (U-Net), whose duty is retrieving the exact shape of the target and its contrast value. This task is cast as an image segmentation one, where each pixel is classified into a discrete set of permittivity values within a given range. The use of a reduced number of possible permittivities facilitates the training stage by limiting its scope. The approach was tested with synthetic data and validated with experimental data taken from the Fresnel database to allow a fair comparison with the literature. Finally, its potential for biomedical imaging is demonstrated with a numerical example related to microwave brain stroke diagnosis.
Hospitalized patients show a high rate of malnutrition, which is associated with poor patient outcomes and high healthcare costs. However, relatively few studies have investigated the association ...between clinical and economic outcomes and malnutrition in hospitalized patients, particularly those with cardiac and pulmonary conditions.
This multicenter prospective observational cohort study included 800 patients hospitalized at four Colombian hospitals with a diagnosis of congestive heart failure, acute myocardial infarction, community-acquired pneumonia, or chronic obstructive pulmonary disease. All patients were screened for malnutrition using the Malnutrition Screening Tool (MST). A descriptive analysis of baseline variables was followed by multivariate analysis and inverse probability weighting (IPW) to compare the clinical outcomes, i.e., length of stay (LOS), mortality, and readmission, and hospital costs associated with a positive MST result.
The prevalence of a positive MST result was 24.62% (n = 197) and was more common in patients with older age and greater comorbidities. Multivariate analysis controlling for age, gender, healthcare plan, university degree, hospitalization, entrance disease and Charlson co-morbidity index showed that a positive MST result was associated with increased LOS (1.43 ± 0.61 days) and both in-hospital mortality (odds ratio, 2.39) and global mortality (odds ratio, 2.52). IPW analysis confirmed the association between a positive MST result and increased hospital LOS and 30-day mortality, as well as a relative increase of 30.13% in the average cost associated with hospitalization.
This study of hospital inpatients demonstrated a high burden of malnutrition at the time of hospital admission, which negatively impacted LOS and mortality and increased the costs of hospitalization. These findings underscore the need for improved diagnosis and treatment of hospital malnutrition to improve patient outcomes and reduce healthcare costs.
Background
Cytoreductive surgery (CRS) and administration of hyperthermic intraperitoneal chemotherapy (HIPEC) have shown their efficacy in multiple malignancies and also could offer a prognostic ...benefit for patients with advanced ovarian cancer.
Methods
A prospective, single-center, parallel-group, randomized phase 3 clinical trial analyzed patients with a diagnosis of carcinomatosis from ovarian cancer treated with neoadjuvant systemic chemotherapy (NACT). In this trial, 71 patients were randomized to receive CRS alone (36 patients) or CRS with HIPEC (35 patients) using cisplatin (75 mg/m
2
for 60 min at 42 °C). The primary end point was disease-free survival (DFS). Overall survival (OS), morbidity, and quality of life (QoL) were the secondary end points.
Results
During a median follow-up period of 32 months, the median DFS was 12 months in the control group (CRS) and 18 months in the experimental group (CRS and HIPEC). The findings showed HIPEC to be an independent protective factor against the development of recurrence (hazard ratio HR, 0.12, 95 % confidence interval CI, 0.02–0.89;
p
= 0.038). The median OS was 45 months in the control group and 52 months in the experimental group. The respective morbidity rates for any grade (1 to 5) were respectively 58.3 % and 45.7 % (
p
> 0.05), with a mortality rates of 2.8 % and 2.9 % (
p
> 0.05). In the dimensions evaluated, CRS with or without HIPEC had no impact on QoL.
Conclusions
For patients who had advanced ovarian cancer treated with NACT, CRS and HIPEC was associated with better DFS and OS, but without a difference in postoperative morbidity, mortality, or in the QoL evaluation.
This study takes a step in understanding the physiological implications of the nanosecond pulsed electric field (nsPEF) by integrating molecular dynamics simulations and machine learning techniques. ...nsPEF, a state-of-the-art technology, uses high-voltage electric field pulses with a nanosecond duration to modulate cellular activity. This investigation reveals a relatively new and underexplored phenomenon: protein-mediated electroporation. Our research focused on the voltage-sensing domain (VSD) of the NaV1.5 sodium cardiac channel in response to nsPEF stimulation. We scrutinized the VSD structures that form pores and thereby contribute to the physical chemistry that governs the defibrillation effect of nsPEF. To do so, we conducted a comprehensive analysis involving the clustering of 142 replicas simulated for 50 ns under nsPEF stimuli. We subsequently pinpointed the representative structures of each cluster and computed the free energy between them. We find that the selected VSD of NaV1.5 forms pores under nsPEF stimulation, but in a way that significant differs from the traditional VSD opening. This study not only extends our understanding of nsPEF and its interaction with protein channels but also adds a new effect to further study.
Quantitative systems pharmacology (QSP) models and spatial agent-based models (ABM) are powerful and efficient approaches for the analysis of biological systems and for clinical applications. ...Although QSP models are becoming essential in discovering predictive biomarkers and developing combination therapies through in silico virtual trials, they are inadequate to capture the spatial heterogeneity and randomness that characterize complex biological systems, and specifically the tumor microenvironment. Here, we extend our recently developed spatial QSP (spQSP) model to analyze tumor growth dynamics and its response to immunotherapy at different spatio-temporal scales. In the model, the tumor spatial dynamics is governed by the ABM, coupled to the QSP model, which includes the following compartments: central (blood system), tumor, tumor-draining lymph node, and peripheral (the rest of the organs and tissues). A dynamic recruitment of T cells and myeloid-derived suppressor cells (MDSC) from the QSP central compartment has been implemented as a function of the spatial distribution of cancer cells. The proposed QSP-ABM coupling methodology enables the spQSP model to perform as a coarse-grained model at the whole-tumor scale and as an agent-based model at the regions of interest (ROIs) scale. Thus, we exploit the spQSP model potential to characterize tumor growth, identify T cell hotspots, and perform qualitative and quantitative descriptions of cell density profiles at the invasive front of the tumor. Additionally, we analyze the effects of immunotherapy at both whole-tumor and ROI scales under different tumor growth and immune response conditions. A digital pathology computational analysis of triple-negative breast cancer specimens is used as a guide for modeling the immuno-architecture of the invasive front.
ΔfosB is an alternatively spliced product of the FosB gene that is essential for dopamine‐induced reward pathways and that acts as a master switch for addiction. However, the molecular mechanisms of ...its generation and regulation by dopamine signaling are unknown. Here, we report that dopamine D1 receptor signaling synergizes with the activin/ALK4/Smad3 pathway to potentiate the generation of ΔFosB mRNA in medium spiny neurons (MSNs) of the nucleus accumbens (NAc) via activation of the RNA‐binding protein PCBP1, a regulator of mRNA splicing. Concurrent activation of PCBP1 and Smad3 by D1 and ALK4 signaling induced their interaction, nuclear translocation, and binding to sequences in exon‐4 and intron‐4 of FosB mRNA. Ablation of either ALK4 or PCBP1 in MSNs impaired ΔFosB mRNA induction and nuclear translocation of ΔFosB protein in response to repeated co‐stimulation of D1 and ALK4 receptors. Finally, ALK4 is required in NAc MSNs of adult mice for behavioral sensitization to cocaine. These findings uncover an unexpected mechanism for ΔFosB generation and drug‐induced sensitization through convergent dopamine and ALK4 signaling.
Synopsis
The molecular and regulatory mechanisms underlying the generation of ΔFosB, an alternatively spliced FosB variant and an essential component of reward pathways and addiction are not well‐understood. Here, dopamine receptor signaling and the activin/ALK4/Smad3 pathway are found to synergistically control the generation of ΔFosB through activation of splicing regulator PCBP1.
Concurrent dopamine and activin A signaling induces phosphorylation, nuclear translocation, and cooperative FosB mRNA intron binding of Smad3 and PCBP1.
Activin A receptor ALK4 synergizes with dopamine D1 receptor to potentiate the generation and nuclear translocation of ∆FosB protein in medium spiny neurons (MSNs) of the nucleus accumbens (NAc).
Ablation of either ALK4 or PCBP1 in MSNs impairs ΔFosB mRNA induction and nuclear translocation of ΔFosB protein in response to repeated co‐stimulation of D1 and ALK4 receptors.
Activin A expression is induced in microglial cells of the NAc upon repeated cocaine stimulation.
ALK4 is required in NAc MSNs of adult mice for behavioral sensitization to cocaine.
Generation of alternative spliced ΔfosB is not constitutive but regulated by dopamine receptor and the activin/ALK4/Smad3 pathway, suggesting new therapeutic avenues for counteracting the effects of drugs of abuse.
Background
Little is known about the achievement of low density lipoprotein cholesterol (LDL-C) targets in patients at cardiovascular risk receiving stable lipid-lowering therapy (LLT) in countries ...outside Western Europe.
Methods
This cross-sectional observational study was conducted in 452 centres (August 2015−August 2016) in 18 countries in Eastern Europe, Asia, Africa, the Middle East and Latin America. Patients (n = 9049) treated for ≥3 months with any LLT and in whom an LDL-C measurement on stable LLT was available within the previous 12 months were included.
Results
The mean±SD age was 60.2 ± 11.7 years, 55.0% of patients were men and the mean ± SD LDL-C value on LLT was 2.6 ± 1.3 mmol/L (101.0 ± 49.2 mg/dL). At enrolment, 97.9% of patients were receiving a statin (25.3% on high intensity treatment). Only 32.1% of the very high risk patients versus 51.9% of the high risk and 55.7% of the moderate risk patients achieved their LDL-C goals. On multivariable analysis, factors independently associated with not achieving LDL-C goals were no (versus lower dose) statin therapy, a higher (versus lower) dose of statin, statin intolerance, overweight and obesity, female sex, neurocognitive disorders, level of cardiovascular risk, LDL-C value unknown at diagnosis, high blood pressure and current smoking. Diabetes was associated with a lower risk of not achieving LDL-C goals.
Conclusions
These observational data suggest that the achievement of LDL-C goals is suboptimal in selected countries outside Western Europe. Efforts are needed to improve the management of patients using combination therapy and/or more intensive LLTs.
The emergence of novelties and their rise and fall in popularity is an ubiquitous phenomenon in human activities. The coexistence of popular evergreens with novel and sometimes ephemeral trends ...pervades technological, scientific and artistic production. Though this phenomenon is very intuitively captured by our common sense, a comprehensive explanation of how waves of novelties are not hampered by well established old-comers is still lacking. Here we first quantify this phenomenology by empirically looking at different systems that display innovation at very different levels: the creation of hashtags in Twitter, the evolution of online code repositories, the creation of texts and the listening of songs on online platforms. In all these systems surprisingly similar patterns emerge as the non-trivial outcome of two contrasting forces: the tendency of retracing already explored avenues (exploit) and the inclination to explore new possibilities. These findings are naturally explained in the framework of the expansion of the adjacent possible, a recently introduced theoretical framework that postulates the restructuring of the space of possibilities conditional to the occurrence of innovations. The predictions of our theoretical framework are borne out in all the phenomenologies investigated, paving the way to a better understanding and control of innovation processes.
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