Miracle-dz/UniFAR-FTUs huggingface dataset:
Multiple Myeloma Patients Undergoing Carfilzomib: Development and Validation of a Risk Score for Cardiovascular Adverse Events Prediction

Simple Summary Despite the relationship between Carfilzomib (CFZ) therapy in multiple myeloma (MM) and cardiovascular adverse events (CVAEs), no specific validated protocols on cardiovascular risk assessment are available. In this prospective study, we investigated major predictors of CVAEs prior to starting CFZ, applying the European Myeloma Network management protocol (EMN). Five predictors were identified: office systolic blood pressure, 24-h blood pressure variability, left ventricular hypertrophy, pulse wave velocity value and global longitudinal strain. The resulting ‘CVAEs risk score’ defined a low- and a high-risk group (negative predicting value for the high-risk group of 90%). 62 patients experienced one or more CVAEs: 17 major and 45 hypertension-related events. In conclusion, CVAEs are frequent and a specific management protocol is required. The EMN protocol and ‘CFZ risk score’ proved to be effective in estimating the baseline risk of CVAEs during CFZ therapy in MM patients, targeting the appropriate follow-up. Abstract Cardiovascular adverse events (CVAEs) are linked to Carfilzomib (CFZ) therapy in multiple myeloma (MM); however, no validated protocols on cardiovascular risk assessment are available. In this prospective study, the effectiveness of the European Myeloma Network protocol (EMN) in cardiovascular risk assessment was investigated, identifying major predictors of CVAEs. From January 2015 to March 2020, 116 MM patients who had indication for CFZ therapy underwent a baseline evaluation (including blood pressure measurements, echocardiography and arterial stiffness estimation) and were prospectively followed. The median age was 64.53 ± 8.42 years old, 56% male. Five baseline independent predictors of CVAEs were identified: office systolic blood pressure, 24-h blood pressure variability, left ventricular hypertrophy, pulse wave velocity value and global longitudinal strain. The resulting ‘CVAEs risk score’ distinguished a low- and a high-risk group, obtaining a negative predicting value for the high-risk group of 90%. 52 patients (44.9%) experienced one or more CVAEs: 17 (14.7%) had major and 45 (38.7%) had hypertension-related events. In conclusion, CVAEs are frequent and a specific management protocol is crucial. The EMN protocol and the risk score proved to be useful to estimate the baseline risk for CVAEs during CFZ therapy, allowing the identification of higher-risk patients.
Thrombin Activatable Fibrinolysis Inhibitor (TAFI): An Updated Narrative Review

Thrombin activatable fibrinolysis inhibitor (TAFI), a proenzyme, is converted to a potent attenuator of the fibrinolytic system upon activation by thrombin, plasmin, or the thrombin/thrombomodulin complex. Since TAFI forms a molecular link between coagulation and fibrinolysis and plays a potential role in venous and arterial thrombotic diseases, much interest has been tied to the development of molecules that antagonize its function. This review aims at providing a general overview on the biochemical properties of TAFI, its (patho)physiologic function, and various strategies to stimulate the fibrinolytic system by interfering with (activated) TAFI functionality.
Effect of Botanical Extracts on the Growth and Nutritional Quality of Field-Grown White Head Cabbage (Brassica oleracea var. capitata)

Nutraceuticals and functional foods are gaining more attention amongst consumers interested in nutritious food. The consumption of foodstuffs with a high content of phytochemicals has been proven to provide various health benefits. The application of biostimulants is a potential strategy to fortify cultivated plants with beneficial bioactive compounds. Nevertheless, it has not yet been established whether the proposed higher plants (St. John’s wort, giant goldenrod, common dandelion, red clover, nettle, and valerian) are appropriate for the production of potential bio-products enhancing the nutritional value of white cabbage. Therefore, this research examines the impact of botanical extracts on the growth and nutritional quality of cabbage grown under field conditions. Two extraction methods were used for the production of water-based bio-products, namely: ultrasound-assisted extraction and mechanical homogenisation. Bio-products were applied as foliar sprays to evaluate their impact on total yield, dry weight, photosynthetic pigments, polyphenols, antioxidant activity, vitamin C, nitrates, micro- and macroelements, volatile compounds, fatty acids, sterols, and sugars. Botanical extracts showed different effects on the examined parameters. The best results in terms of physiological and biochemical properties of cabbage were obtained for extracts from common dandelion, valerian, nettle, and giant goldenrod. When enriched with nutrients, vegetables can constitute a valuable component of functional food.
Associations between Housing Factors and Respiratory Symptoms in Two Saskatchewan First Nations Communities

Inadequate housing is commonplace in First Nations in Canada, often leading to environmental impacts on housing such as dampness and mold. First Nations communities suffer from a higher prevalence of respiratory-related health conditions than the general Canadian population. There is limited Canadian literature evaluating the relationship between housing factors and the respiratory health of adults within First Nations communities. This study was undertaken with two Saskatchewan First Nations communities. The study population consisted of 293 individuals within 131 households. The individuals completed questionnaires on their general and respiratory health, and one member of each household completed a household questionnaire. The collection of environmental samples from within the house was undertaken. The respiratory outcomes of interest focused on the individuals with ever wheeze, reported by 77.8% of the individuals, and shortness of breath, reported by 52.6% of the individuals. Body mass index, the nontraditional use of tobacco (i.e., current and ex-smoking), the nontraditional use of tobacco in the house (i.e., smoking in the house), dampness in the house in the last 12 months, and always having a smell of mold in the house were significantly associated with respiratory symptoms. The results reveal that respiratory symptom rates were high in the population and housing factors were significantly associated with respiratory symptoms. Addressing and redressing housing inadequacies in First Nations communities are important in preventing additional burdens to health.
Ex Vivo High Salt Activated Tumor-Primed CD4+T Lymphocytes Exert a Potent Anti-Cancer Response

Simple Summary Cell based immunotherapy is rapidly emerging as a promising cancer treatment. Salt (sodium chloride) treatment to immune cell cultures is known to induce inflammatory activation. In our current study, we analyzed the anti-cancer ability of salt treatment on immune cells outside the host followed by reinfusion into the host. Using a pre-clinical breast cancer model, we demonstrated that external salt treatment on T-cell subset of immune cells produced a viable anti-cancer response, which may have future human clinical application. Abstract Cell based immunotherapy is rapidly emerging as a promising cancer treatment. A modest increase in salt (sodium chloride) concentration in immune cell cultures is known to induce inflammatory phenotypic differentiation. In our current study, we analyzed the ability of salt treatment to induce ex vivo expansion of tumor-primed CD4 (cluster of differentiation 4)+T cells to an effector phenotype. CD4+T cells were isolated using immunomagnetic beads from draining lymph nodes and spleens from tumor bearing C57Bl/6 mice, 28 days post-injection of Py230 syngeneic breast cancer cells. CD4+T cells from non-tumor bearing mice were isolated from splenocytes of 12-week-old C57Bl/6 mice. These CD4+T cells were expanded ex vivo with five stimulation cycles, and each cycle comprised of treatment with high salt (Δ0.035 M NaCl) or equimolar mannitol controls along with anti-CD3/CD28 monoclonal antibodies for the first 3 days, followed by the addition of interleukin (IL)-2/IL-7 cytokines and heat killed Py230 for 4 days. Ex vivo high salt treatment induced a two-fold higher Th1 (T helper type 1) expansion and four-fold higher Th17 expansion compared to equimolar mannitol treatment. Importantly, the high salt expanded CD4+T cells retained tumor-specificity, as demonstrated by higher in vitro cytotoxicity against Py230 breast cancer cells and reduced in vivo syngeneic tumor growth. Metabolic studies revealed that high salt treatment enhanced the glycolytic reserve and basal mitochondrial oxidation of CD4+T cells, suggesting a role of high salt in enhanced pro-growth anabolic metabolism needed for inflammatory differentiation. Mechanistic studies demonstrated that the high salt induced switch to the effector phenotype was mediated by tonicity-dependent transcription factor, TonEBP/NFAT5. Using a transgenic murine model, we demonstrated that CD4 specific TonEBP/NFAT5 knock out (CD4cre/creNFAT5flox/flox) abrogated the induction of the effector phenotype and anti-tumor efficiency of CD4+T cells following high salt treatment. Taken together, our data suggest that high salt-mediated ex vivo expansion of tumor-primed CD4+T cells could induce effective tumor specific anti-cancer responses, which may have a novel cell-based cancer immunotherapeutic application.
The Consumption of Cholesterol-Enriched Diets Conditions the Development of a Subtype of HCC with High Aggressiveness and Poor Prognosis

Simple Summary It is well known that non-alcoholic fatty liver disease is an important risk factor in the development of hepatocellular carcinoma, but the implication of cholesterol in this subject remains unclear, especially in western countries where its consumption is particularly elevated. This work provides evidence of a cholesterol-related transcriptional fingerprint and its implications in the progression and aggressiveness of hepatocellular carcinoma with remarkable interest in clinical practice. Abstract Non-alcoholic fatty liver disease (NAFLD) and progression to non-alcoholic steatohepatitis (NASH) result as a consequence of diverse conditions, mainly unbalanced diets. Particularly, high-fat and cholesterol content, as well as carbohydrates, such as those commonly ingested in Western countries, frequently drive adverse metabolic alterations in the liver and promote NAFLD development. Lipid liver overload is also one of the main risk factors for initiation and progression of hepatocellular carcinoma (HCC), but detailed knowledge on the relevance of high nutritional cholesterol remains elusive. We were aimed to characterize HCC development in mice fed with a Western diet (high in lipids and cholesterol) and to identify molecular alterations that define a subtype of liver cancer induced by lipid overload. Mice under western or high cholesterol diets more frequently developed tumors with a more aggressive phenotype than animals fed with a chow diet. Associated changes involved macrophage infiltration, angiogenesis, and stemness features. RNA-seq revealed a specific gene expression signature (Slc41a; Fabp5; Igdcc4 and Mthfd1l) resembling the adverse phenotypic features and poor clinical outcomes seen in patients with HCC. In conclusion; consumption of lipid enriched diets; particularly cholesterol; could accelerate HCC development with an aggressive phenotype and poor prognosis
Pregnancy and Cancer: Cellular Biology and Mechanisms Affecting the Placenta

Simple Summary The main point of this review was to describe most of the mechanisms of the biology of trophoblast cells and neoplastic cells, which point out some similarities between them and the way in which both complex metabolic states could interfere with each other. We show the need for more studies about cancer during pregnancy. In addition, the magnitude of how tumour factors can interfere with the course of pregnancy and affect the foetus’s nutrition and health is the most important point that should be studied to better understand and improve treatment for this complex condition. In this context, we have highlighted the importance of maternal nutritional supplementation with leucine, a branched-chain amino acid that improves the placenta’s metabolism and protects the mother and foetus against the harmful effects of cancer during pregnancy. Abstract Cancer during pregnancy is rarely studied due to its low incidence (1:1000). However, as a result of different sociocultural and economic changes, women are postponing pregnancy, so the number of pregnant women with cancer has been increasing in recent years. The importance of studying cancer during pregnancy is not only based on maternal and foetal prognosis, but also on the evolutionary mechanisms of the cell biology of trophoblasts and neoplastic cells, which point out similarities between and suggest new fields for the study of cancer. Moreover, the magnitude of how cancer factors can affect trophoblastic cells, and vice versa, in altering the foetus’s nutrition and health is still a subject to be understood. In this context, the objective of this narrative review was to show that some researchers point out the importance of supplementing branched-chain amino acids, especially leucine, in experimental models of pregnancy associated with women with cancer. A leucine-rich diet may be an interesting strategy to preserve physiological placenta metabolism for protecting the mother and foetus from the harmful effects of cancer during pregnancy.
Inhibition of Liver Metastasis in Colorectal Cancer by Targeting IL-13/IL13Rα2 Binding Site with Specific Monoclonal Antibodies

Simple Summary IL13Rα2 has been repeatedly reported as an excellent therapeutic target for multiple types of advanced cancers. However, previous IL13Rα2 targeting attempts have been mostly unsuccessful. Here, we describe a novel strategy based on the blocking of the IL-13 tumorigenic activity using a highly preserved D1 peptide selected from the IL13Rα2 binding site for mouse immunization and the inhibition of the cell invasion capacity for antibody screening. The IL13Rα2 D1 peptide-specific monoclonal antibody 5.5. 4 has demonstrated a large capacity for blocking IL13Rα2 signaling capacity and protecting mice against established and non-established liver metastasis in colorectal cancer. These positive results predict a potential application to other IL13Rα2 positive cancers. Abstract Background: IL13Rα2 is reportedly a promising therapeutic target in different cancers. Still, no specific antagonists have reached the clinics yet. We investigated the use of a IL-13/IL13Rα2 binding motif, called D1, as a new target for the development of therapeutic monoclonal antibodies (mAbs) for colorectal cancer (CRC) metastasis. Methods: IL13Rα2 D1 peptides were prepared and used for immunization and antibody development. Antibodies were tested for inhibition of cellular invasion through Matrigel using CRC cell lines. Effects of the mAbs on cell signaling, receptor internalization and degradation were determined by western blot and flow cytometry. Swiss nude mice were used for survival analysis after treatment with IL13Rα2-specific mAbs and metastasis development. Results: IL13Rα2 D1 peptides were used to generate highly selective mAbs that blocked IL13/IL13Rα2-mediated SRC activation and cell invasion in colorectal cancer cells. Antibodies also provoked a significant reduction in cell adhesion and proliferation of metastatic cancer cells. Treatment with mAbs impaired the FAK, SRC and PI3K/AKT pathway activation. Blocking effectivity was shown to correlate with the cellular IL13Rα2 expression level. Despite mAb 5.5. 4 partially blocked IL-13 mediated receptor internalization from the cancer cell surface it still promotes receptor degradation. Compared with other IL13Rα2-specific antibodies, 5.5. 4 exhibited a superior efficacy to inhibit metastatic growth in vivo, providing a complete mouse survival in different conditions, including established metastasis. Conclusions: Monoclonal antibody 5.5. 4 showed a highly selective blocking capacity for the interaction between IL-13 and IL13Rα2 and caused a complete inhibition of liver metastasis in IL13Rα2-positive colorectal cancer cells. This capacity might be potentially applicable to other IL13Rα2-expressing tumors.
Design of Minimum Nonlinear Distortion Reconfigurable Antennas for Next-Generation Communication Systems

Nonlinear effects in the radio front-end can degrade communication quality and system performance. In this paper we present a new design technique for reconfigurable antennas that minimizes the nonlinear distortion and maximizes power efficiency through the minimization of the coupling between the internal switching ports and the external feeding ports. As a nonlinear design and validation instance, we present the nonlinear characterization up to 50 GHz of a PIN diode commonly used as a switch for reconfigurable devices in the microwave band. Nonlinear models are extracted through X-parameter measurements supported by accurate calibration and de-embedding procedures. Nonlinear switch models are validated by S-parameter measurements in the low power signal regime and by harmonic measurements in the large-signal regime and are further used to predict the measured nonlinearities of a reconfigurable antenna. These models have the desired particularity of being integrated straightforwardly in the internal multi-port method formulation, which is used and extended to account for the power induced on the switching elements. A new figure of merit for the design of reconfigurable antennas is introduced—the power margin, that is, the power difference between the fed port and the switching elements, which combined with the nonlinear load models directly translates into nonlinearities and power-efficiency-related metrics. Therefore, beyond traditional antenna aspects such as port match, gain, and beam orientation, switch power criteria are included in the design methodology. Guidelines for the design of reconfigurable antennas and parasitic layers of minimum nonlinearity are provided as well as the inherent trade-offs. A particular antenna design suitable for 5G communications in the 3.5 GHz band is presented according to these guidelines, in which the specific switching states for a set of target performance metrics are obtained via a balancing of the available figures of merit with multi-objective separation criteria, which enables good control of the various design trade-offs. Average Error Vector Magnitude (EVM) and power efficiency improvement of 12 and 6 dB, respectively, are obtained with the application of this design approach. In summary, this paper introduces a new framework for the nonlinear modeling and design of reconfigurable antennas and provides a set of general-purpose tools applicable in cases beyond those used as examples and validation in this work. Additionally, the use of these models and guidelines is presented, demonstrating one of the most appealing advantages of the reconfigurable parasitic layer approach, their low nonlinearity.
Biochar from Pine Wood, Rice Husks and Iron-Eupatorium Shrubs for Remediation Applications: Surface Characterization and Experimental Tests for Trichloroethylene Removal

Nowadays porous materials from organic waste, i.e., Biochar (BC), are receiving increased attention for environmental applications. This study adds information on three BCs that have undergone a number of studies in recent years. A Biochar from pine wood, one from rice husk and one from Eupatorium shrubs enriched with Iron, labelled as PWBC, RHBC and EuFeBC respectively, are evaluated for Trichloroethylene (TCE) removal from aqueous solution. Physical-chemical description is performed by SEM-EDS and BET analysis. The decrease of TCE over time follows a pseudo-second order kinetics with increased removal by the PWBC. Freundlich and Langmuir models well fit equilibrium test data. The optimized values of the maximum adsorbed amount, qmax (mg g−1), follows this order 109.41 PWBC > 30.35 EuFeBC > 21.00 RHBC. Fixed-bed columns are also carried out. Best performance is again achieved by PWBC, which operates for a higher number of pore volume, followed by EuFeBC and RHBC. Continuous testing confirms batch studies and makes it possible to evaluate the workability of materials in configurations closer to reality. Results are promising for potential environmental application. In particular, the characterization of several classes of contaminants opens the doors to possible uses in mixed contamination cases.
Influence of Salt on the Self-Organization in Solutions of Star-Shaped Poly-2-alkyl-2-oxazoline and Poly-2-alkyl-2-oxazine on Heating

The water–salt solutions of star-shaped six-arm poly-2-alkyl-2-oxazines and poly-2-alkyl-2-oxazolines were studied by light scattering and turbidimetry. The core was hexaaza[26]orthoparacyclophane and the arms were poly-2-ethyl-2-oxazine, poly-2-isopropyl-2-oxazine, poly-2-ethyl-2-oxazoline, and poly-2-isopropyl-2-oxazoline. NaCl and N-methylpyridinium p-toluenesulfonate were used as salts. Their concentration varied from 0–0.154 M. On heating, a phase transition was observed in all studied solutions. It was found that the effect of salt on the thermosensitivity of the investigated stars depends on the structure of the salt and polymer and on the salt content in the solution. The phase separation temperature decreased with an increase in the hydrophobicity of the polymers, which is caused by both a growth of the side radical size and an elongation of the monomer unit. For NaCl solutions, the phase separation temperature monotonically decreased with growth of salt concentration. In solutions with methylpyridinium p-toluenesulfonate, the dependence of the phase separation temperature on the salt concentration was non-monotonic with minimum at salt concentration corresponding to one salt molecule per one arm of a polymer star. Poly-2-alkyl-2-oxazine and poly-2-alkyl-2-oxazoline stars with a hexaaza[26]orthoparacyclophane core are more sensitive to the presence of salt in solution than the similar stars with a calix[n]arene branching center.
The Applicability of the Poincaré Plot in the Analysis of Variability of Reaction Time during Serial Testing

(1) Background: This study aims to put into evince the relationship between the variability of the reaction time (RT) during repeated testing, expressed through indicators extracted by the Poincaré plot method, and the age of the participants, their self-reported health (SRH), and level of perceived anxiety. (2) Methods: The study was performed using computerized RT testing software. An observational cross-sectional study was performed on a group of 120 subjects (mean age 42.33 ± 21.12 years), sex ratio men to women 1.14:1. Data were processed through descriptive and inferential statistics. The Poincaré plot method was applied in the analysis of the RT series of data, by calculating the indicators SD1, SD2, SD1/SD2, and area of the fitting ellipse (AFE) (3) Results: We provided evidence of the excellent reliability of the web-based RT serial testing (Cronbach’s Alpha 0.991) with this sample group. Our results showed that age is an important predictor for mean values of RT, while SD1, SD2, and AFE indicators are for SRH (p < 0.01). (4) Conclusions: the variability of RT, expressed by the Poincaré plot indicators, reflects the health status rather than the aging of the subjects and is barely influenced by their level of anxiety.