Miracle-dz/UniFAR-FTUs huggingface dataset:
A Combination of Cabozantinib and Radiation Does Not Lead to an Improved Growth Control of Tumors in a Preclinical 4T1 Breast Cancer Model

The tyrosine kinase inhibitor Cabozantinib has been applied in clinical studies in combination with radiotherapy. We investigated the effect of such combination on triple-negative 4T1 cells as a metastatic breast cancer model in vitro and in vivo upon inoculation in BALB/c mice. In vitro assays indicated a potential for improved effects using the combination. Both Cabozantinib (2.5 µM) and 10 Gy of 250 kV x-rays were able to cease the growth of 4T1 cells as revealed by growth curves. In a clonogenic survival assay, the effect of Cabozantinib added on the effects of irradiation and the effectiveness of inhibiting the clonogenic survival was found to be 2 (RBE10). Additionally, cell death measurements of apoptosis plus necrosis revealed a synergistic effect when combining irradiation with Cabozantinib. Surprisingly, however, in vivo tumor growth kinetics showed no additional effect in growth control when irradiation was used together with Cabozantinib. Since both ionizing radiation and Cabozantinib are acknowledged to feature immunogenic effects, we additionally investigated the effect of the treatments on lung metastases. No difference to the control groups was found here, neither for irradiation nor Cabozantinib alone nor in combination. Yet, upon analysis of the mice’ livers, CD11b-positive cells, indicating immune suppressive myeloid derived suppressor cells were found diminished following treatment with Cabozantinib. In conclusion, despite promising in vitro controls of the combination of Cabozantinib and irradiation, tumor growth control was not increased by the combination, which was true also for the occurrence of lung metastases.
Combination of Early Allograft Dysfunction and Protein Expression Patterns Predicts Outcome of Liver Transplantation From Donation After Cardiac Death

Early allograft dysfunction (EAD) after liver transplantation (LT) accompanies poor prognosis. This study aims to explore the relationship between pretransplant intrahepatic proteins and the incidence of EAD, and the value of combined EAD and protein profiles for predicting recipient and graft survival prognosis. Liver biopsy specimens of 105 pretransplant grafts used for LT were collected and used for immunohistochemistry analysis of 5 proteins. And matched clinical data of donor, recipient, transplantation, and prognosis were analyzed. The incidence of EAD was 41.9% (44/105) in this cohort. Macrovesicular steatosis (P = 0.016), donor body mass index (P = 0.013), recipients' pretransplant serum creatinine (P = 0.036), and intrahepatic expression of heme oxygenase 1 (HO1) (P = 0.015) and tumor necrosis factor α (TNF-α) (P = 0.039) were independent predictors of EAD. Inferior graft and recipient prognosis were observed in patients who experienced EAD (P = 0.028 and 0.031) or received grafts with higher expression of sirtuin 1 (P = 0.005 and 0.013). The graft and recipient survival were worst in patients with both EAD and high expression of sirtuin 1 (P = 0.001 and 0.004). In conclusion, pretransplant intrahepatic expression of HO1 and TNF-α are associated with the incidence of EAD. The combination of EAD and EAD-unrelated proteins showed superiority in distinguishing recipients with worse prognosis.
Angioedema Without Wheals: Challenges in Laboratorial Diagnosis

Angioedema is a prevailing symptom in different diseases, frequently occurring in the presence of urticaria. Recurrent angioedema without urticaria (AE) can be hereditary (HAE) and acquired (AAE), and several subtypes can be distinguished, although clinical presentation is quite similar in some of them. They present with subcutaneous and mucosal swellings, affecting extremities, face, genitals, bowels, and upper airways. AE is commonly misdiagnosed due to restricted access and availability of appropriate laboratorial tests. HAE with C1 inhibitor defect is associated with quantitative and/or functional deficiency. Although bradykinin-mediated disease results mainly from disturbance in the kallikrein–kinin system, traditionally complement evaluation has been used for diagnosis. Diagnosis is established by nephelometry, turbidimetry, or radial immunodiffusion for quantitative measurement of C1 inhibitor, and chromogenic assay or ELISA has been used for functional C1-INH analysis. Wrong handling of the samples can lead to misdiagnosis and, consequently, mistaken inappropriate approaches. Dried blood spot (DBS) tests have been used for decades in newborn screening for certain metabolic diseases, and there has been growing interest in their use for other congenital conditions. Recently, DBS is now proposed as an efficient tool to diagnose HAE with C1 inhibitor deficiency, and its use would improve the access to outbound areas and family members. Regarding HAE with normal C1 inhibitor, complement assays’ results are normal and the genetic sequencing of target genes, such as exon 9 of F12 and PLG, is the only available method. New methods to measure cleaved high-molecular-weight kininogen and activated plasma kallikrein have emerged as potential biochemical tests to identify bradykinin-mediated angioedema. Validated biomarkers of kallikrein–kinin system activation could be helpful in differentiating mechanisms of angioedema. Our aim is to focus on the capability to differentiate histaminergic AE from bradykinin-mediated AE. In addition, we will describe the challenges developing specific tests like direct bradykinin measurements. The need for quality tests to improve the diagnosis is well represented by the variability of results in functional assays.
A Multi-Faceted Approach to Understand How Resource Diversity Can Mediate the Coexistence of Cryptic Marine Nematode Species

Based on the principle of competitive exclusion, species occupying the same ecological niche cannot stably coexist due to strong interspecific competition for resources. Niche diversification, for instance through resource partitioning, may alleviate competition. Here, we investigate the effects of resource diversity on foraging behavior, fitness and interspecific interactions of four cryptic bacterivorous nematode species (Pm I–IV) of the Litoditis marina species complex with sympatric field distributions. Three resource (bacteria) diversity levels (low, medium, high) were used as food treatments and compared to a treatment with only Escherichia coli as food. Differences in taxis to food existed between the cryptic species and between bacterial mixtures of different diversity: all the cryptic species except Pm I showed higher attraction toward medium-diversity food. Furthermore, the cryptic species of L. marina generally exhibited higher fitness on a more diverse food resource. Resource diversity also impacted the interspecific interactions between the cryptic species. Our results show that resource diversity can alter the interspecific interactions among the cryptic species of L. marina, indicating that competitive equilibria between species are very context-dependent. Although a considerable body of evidence supports the hypotheses (e.g., “variance-in-edibility” hypothesis and the “dilution hypothesis” or “resource concentration hypothesis”) which predict a negative impact on consumers when resource diversity is increased, the benefits of a diverse resource can outweigh these disadvantages by offering a more complete and/or complementary range of nutritional resources as suggested by the “balanced diet” hypothesis.
Turbulent flow within a random array of rigid, emergent stems : Laboratory characterization of the drag coefficient

Within the bioengineering framework, designing a non-erodible channel is a complex fluid dynamics problem as it involves knowing the drag exerted on the boundary, the drag exerted on the plant stems and the overall friction slope. Most of the existing design criteria employ resistance formulas such as Manning’s, calibrated ad hoc. Moving toward physically based design criteria, progresses have been made in the characterization of 3D flows over irregular boundaries, mainly due to the application of Double-Averaging methods (D-AM), which are a particular form of upscaling. Such methods are especially pertinent for the characterization of the flow within and in the near vicinity of plant canopies.This work is aimed at the determination of the drag coefficient associated to rigid emergent stems in turbulent flows. Specific objectives are i) the detailed characterization and quantification of the flow within vegetated areas susceptible to be simulated by dense arrays of vertical emergent stems and ii) the independent quantification of the forces, per unit bed area, acting on the stems and on the bed boundary. Both objectives concur for a better knowledge of the flow resistance in wetlands and vegetated areas in general. To meet the proposed objectives, conditions similar to those found in nature were reproduced in laboratory facilities, using Particle Image Velocimetry (PIV). Since actual wetlands exhibit patchiness and spatial variability in stem density, the experiments featured a periodic distribution of stem densities with minimum and maximum values of 400 and 1600 stems/m2, respectively. The treatment of the data was done with the Double-Averaging methodology (D-AM), to account for the great spatial variability of the flow. The results reveal that the contribution of form-induced stresses, namely longitudinal and shear stresses is of the order of magnitude of the contribution of Reynolds stresses. Hence, in general, this stresses cannot be neglected. The analysis of form-induced stresses helps to explain the increase of the drag coefficient when the stem density increases.
Effect of Tempo on Temporal Expectation Driven by Rhythms in Dual-Task Performance

Temporal expectation is the ability to focus attention at a particular moment in time to optimize performance, which has been shown to be driven by regular rhythms. However, whether the rhythm-based temporal expectations rely upon automatic processing or require the involvement of controlled processing has not been clearly established. Furthermore, whether the mechanism is affected by tempo remains unknown. To investigate this research question, the present study used a dual-task procedure. In a single task, the participants were instructed to respond to a visual target preceded by a regular or an irregular visual rhythm under a fast (500 ms) or slow (3,500 ms) tempo. The dual-task simultaneously combined a working memory (WM) task. The results showed temporal expectation effects in which the participants responded faster to the regular than to the irregular conditions in a single task. Moreover, this effect persisted under dual-task interference in the fast tempo condition but was impaired in the slow tempo condition. These results revealed that rhythmic temporal expectation induced by fast tempo was dependent on automatic processing. However, compared with the faster tempo, temporal expectation driven by a slower tempo might involve more controlled processing.
Hypoxia Contributes to Poor Prognosis in Primary IDH-wt GBM by Inducing Tumor Cells MES-Like Transformation Trend and Inhibiting Immune Cells Activity

Aims To reveal the influence of hypoxia on tumor cells and immune cells in primary IDH-wt glioblastoma patients. Methods Single-cell RNA-seq data and bulk RNA-seq data were acquired from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, respectively. Hypoxia status and subtypes of tumor cells were identified based on single-sample Gene Set Enrichment Analysis (ssGSEA). Regulon network analysis of different subtypes under different conditions was conducted by SCENIC. Within tumor microenvironment, biological process activity analysis and cell–cell communication network were conducted to uncover the inner links between each cell subtype under different hypoxia status. Results Different types of tumor cell in GBM possessed different hypoxia status, and MES-like subtype was under a more severe hypoxia condition than other subtypes. Hypoxia also induced MES-like signature gene expression within each tumor cell, which could stimulate tumor cell proliferation and invasion by regulating cell–cell communication. Additionally, hypoxia inhibited immune cell activity in the tumor microenvironment by inducing macrophage phenotype polarization and upregulating immune-inhibited cell–cell interaction within immune cells. Interactions between tumor cells and immune cells under hypoxia status also promoted tumor progression. Conclusions Hypoxia was a poor prognostic marker for primary IDH-wt GBM patients. Meanwhile, it could induce tumor cells’ MES-like transformation trend and inhibit antitumor function of immune cells.
Hierarchical Spatio-Temporal Modeling of Naturalistic Functional Magnetic Resonance Imaging Signals via Two-Stage Deep Belief Network With Neural Architecture Search

Naturalistic functional magnetic resonance imaging (NfMRI) has become an effective tool to study brain functional activities in real-life context, which reduces the anxiety or boredom due to difficult or repetitive tasks and avoids the problem of unreliable collection of brain activity caused by the subjects’ microsleeps during resting state. Recent studies have made efforts on characterizing the brain’s hierarchical organizations from fMRI data by various deep learning models. However, most of those models have ignored the properties of group-wise consistency and inter-subject difference in brain function under naturalistic paradigm. Another critical issue is how to determine the optimal neural architecture of deep learning models, as manual design of neural architecture is time-consuming and less reliable. To tackle these problems, we proposed a two-stage deep belief network (DBN) with neural architecture search (NAS) combined framework (two-stage NAS-DBN) to model both the group-consistent and individual-specific naturalistic functional brain networks (FBNs), which reflected the hierarchical organization of brain function and the nature of brain functional activities under naturalistic paradigm. Moreover, the test-retest reliability and spatial overlap rate of the FBNs identified by our model reveal better performance than that of widely used traditional methods. In general, our model provides a promising method for characterizing hierarchical spatiotemporal features under the natural paradigm.
Nutritional and Functional Properties of Wild Leafy Vegetables for Improving Food Security in Southern Angola

In Southern Angola, numerous non-woody forest products are sold at local markets, namely in Lubango (Huíla Province). Such is the case of herbaceous wild plants, locally known as lombi, which are sold fresh throughout the year and cooked as a vegetable. Although these wild leafy vegetables are commercialized and widely used in local food, there is still a lack of scientific knowledge about their properties. Thus, this study aimed to identify and characterize the species sold, and to determine their nutritional and functional properties. Our results revealed that three species—Amaranthus hybridus, Bidens pilosa, and Galinsoga parviflora—are usually sold at Lubango markets and consumed by local populations. These are annual exotic plants, native to Southern America, and usually occur spontaneously in croplands or disturbed areas, but can also be cultivated, particularly A. hybridus. Physico-chemical analyses of lombi species and mixtures sold at the markets included measurements of moisture, protein, lipid, and mineral content, as well as total phenolic content, antioxidant activity, and levels of heavy metal contaminants. The results revealed that lombi contain a significant amount of protein (20–28 g/100 g, dry basis), high values of macronutrients and micronutrients, as well as of phenolic compounds (10–40 mg GAE/g) and a good antioxidant capacity. Given the availability of lombi throughout the year, our study demonstrated the importance of wild edible plants in Angola, both as a valuable natural resources and as a complementary food sources, as well as additional sources of income for many families.
Metabolomic Profile of Skeletal Muscle and Its Change Under a Mixed-Mode Exercise Intervention in Progressively Dysglycemic Subjects

Skeletal muscles play an essential role in whole-body glucose homeostasis. They are a key organ system engaged in the development of insulin resistance, and also a crucial tissue mediating the beneficial metabolic effects of physical activity. However, molecular mechanisms underlying both these processes in skeletal muscle remain unclear. The aim of our study was to compare metabolomic profiles in skeletal muscle of patients at different stages of dysglycemia, from normoglycemia through prediabetes to T2D, and its changes under a mixed-mode (strength and endurance) exercise intervention. We performed targeted metabolomics comprising several major metabolite classes, including amino acids, biogenic amines and lipid subgroups in skeletal muscles of male patients. Dysglycemic groups differed significantly at baseline in lysophosphatidylcholines, phosphatidylcholines, sphingomyelins, glutamine, ornithine, and carnosine. Following the exercise intervention, we detected significant changes in lipids and metabolites related to lipid metabolism, including in ceramides and acylcarnitines. With their larger and more significant change over the intervention and among dysglycemic groups, these findings suggest that lipid species may play a predominant role in both the pathogenesis of type 2 diabetes and its protection by exercise. Simultaneously, we demonstrated that amino acid metabolism, especially glutamate dysregulation, is correlated to the development of insulin resistance and parallels disturbances in lipid metabolites.
Regulation of Mating-Induced Increase in Female Germline Stem Cells in the Fruit Fly Drosophila melanogaster

In many insect species, mating stimuli can lead to changes in various behavioral and physiological responses, including feeding, mating refusal, egg-laying behavior, energy demand, and organ remodeling, which are collectively known as the post-mating response. Recently, an increase in germline stem cells (GSCs) has been identified as a new post-mating response in both males and females of the fruit fly, Drosophila melanogaster. We have extensively studied mating-induced increase in female GSCs of D. melanogaster at the molecular, cellular, and systemic levels. After mating, the male seminal fluid peptide [e.g. sex peptide (SP)] is transferred to the female uterus. This is followed by binding to the sex peptide receptor (SPR), which evokes post-mating responses, including increase in number of female GSCs. Downstream of SP-SPR signaling, the following three hormones and neurotransmitters have been found to act on female GSC niche cells to regulate mating-induced increase in female GSCs: (1) neuropeptide F, a peptide hormone produced in enteroendocrine cells; (2) octopamine, a monoaminergic neurotransmitter synthesized in ovary-projecting neurons; and (3) ecdysone, a steroid hormone produced in ovarian follicular cells. These humoral factors are secreted from each organ and are received by ovarian somatic cells and regulate the strength of niche signaling in female GSCs. This review provides an overview of the latest findings on the inter-organ relationship to regulate mating-induced female GSC increase in D. melanogaster as a model. We also discuss the remaining issues that should be addressed in the future.
The Na+/Ca2+ Exchanger 3 Is Functionally Coupled With the NaV1.6 Voltage-Gated Channel and Promotes an Endoplasmic Reticulum Ca2+ Refilling in a Transgenic Model of Alzheimer’s Disease

The remodelling of neuronal ionic homeostasis by altered channels and transporters is a critical feature of the Alzheimer’s disease (AD) pathogenesis. Different reports converge on the concept that the Na+/Ca2+ exchanger (NCX), as one of the main regulators of Na+ and Ca2+ concentrations and signalling, could exert a neuroprotective role in AD. The activity of NCX has been found to be increased in AD brains, where it seemed to correlate with an increased neuronal survival. Moreover, the enhancement of the NCX3 currents (INCX) in primary neurons treated with the neurotoxic amyloid β 1–42 (Aβ1–42) oligomers prevented the endoplasmic reticulum (ER) stress and neuronal death. The present study has been designed to investigate any possible modulation of the INCX, the functional interaction between NCX and the NaV1.6 channel, and their impact on the Ca2+ homeostasis in a transgenic in vitro model of AD, the primary hippocampal neurons from the Tg2576 mouse, which overproduce the Aβ1–42 peptide. Electrophysiological studies, carried in the presence of siRNA and the isoform-selective NCX inhibitor KB-R7943, showed that the activity of a specific NCX isoform, NCX3, was upregulated in its reverse, Ca2+ influx mode of operation in the Tg2576 neurons. The enhanced NCX activity contributed, in turn, to increase the ER Ca2+ content, without affecting the cytosolic Ca2+ concentrations of the Tg2576 neurons. Interestingly, our experiments have also uncovered a functional coupling between NCX3 and the voltage-gated NaV1.6 channels. In particular, the increased NaV1.6 currents appeared to be responsible for the upregulation of the reverse mode of NCX3, since both TTX and the Streptomyces griseolus antibiotic anisomycin, by reducing the NaV1.6 currents, counteracted the increase of the INCX in the Tg2576 neurons. In agreement, our immunofluorescence analyses revealed that the NCX3/NaV1.6 co-expression was increased in the Tg2576 hippocampal neurons in comparison with the WT neurons. Collectively, these findings indicate that NCX3 might intervene in the Ca2+ remodelling occurring in the Tg2576 primary neurons thus emerging as a molecular target with a neuroprotective potential, and provide a new outcome of the NaV1.6 upregulation related to the modulation of the intracellular Ca2+ concentrations in AD neurons.
Ruminal Phages – A Review

The rumen ecosystem is a complex and dynamic environment, which hosts microorganisms including archaea, bacteria, protozoa, fungi, and viruses. These microorganisms interact with each other, altering the ruminal environment and substrates that will be available for the host digestion and metabolism. Viruses can infect the host and other microorganisms, which can drive changes in microorganisms’ lysis rate, substrate availability, nutrient recycling, and population structure. The lysis of ruminal microorganisms’ cells by viruses can release enzymes that enhance feedstuff fermentation, which may increase dietary nutrient utilization and feed efficiency. However, negative effects associated to viruses in the gastrointestinal tract have also been reported, in some cases, disrupting the dynamic stability of the ruminal microbiome, which can result in gastrointestinal dysfunctions. Therefore, the objective of this review is to summarize the current knowledge on ruminal virome, their interaction with other components of the microbiome and the effects on animal nutrition. Graphical Abstract Ruminal viruses can interact with all groups of microorganisms in the ruminal environment, which include bacteria, archaea, fungi, and protozoa. Physical-chemical parameters of the ruminal environment, such as pH, concentration of volatile fatty acids (VFA), ammonia, and other chemical components, can be modulated by the animal’s diet. We hypothesized that such changes in the physical-chemical parameters of the ruminal environment can modify the infectivity of viral particles and change the lysis rate of microbial cells, consequently, changes on VFA production and microbial biomass could affect animals’ performance.