Miracle-dz/UniFAR-FTUs huggingface dataset:
Liquid Biopsy as a Diagnostic and Prognostic Tool for Women and Female Dogs with Breast Cancer

Simple Summary Breast cancer (BC) has common characteristics in women and female dogs, such as high recurrence, metastasis, and mortality rate. In both species, BC prognosis is limited due to its heterogeneous molecular aspects. Although conventional biopsy remains the gold standard for BC diagnosis, liquid biopsy is a very promising tool, especially for patient follow-up. We investigated the effectiveness of liquid biopsy in the diagnosis and follow-up of women and female dogs with BC, using both core biopsy and plasma samples processed by next generation sequencing (NGS) assay. We noted that NGS is a sophisticated technique generating multiple and complex results, which must be validated. Notably, the number of genetic variants increased as the disease progressed. We conclude that liquid biopsy can be considered more effective when performed from the onset of the disease and continues to be applied for monitoring the follow up of BC patients, helping to drive the clinician’s decision for medical intervention. Abstract Introduction: Breast cancer (BC) is the malignant neoplasm with the highest mortality rate in women and female dogs are good models to study BC. Objective: We investigated the efficacy of liquid biopsy to detect gene mutations in the diagnosis and follow-up of women and female dogs with BC. Materials and Methods: In this study, 57 and 37 BC samples were collected from women and female dogs, respectively. After core biopsy and plasma samples were collected, the DNA and ctDNA of the tumor fragments and plasma were processed for next generation sequencing (NGS) assay. After preprocessing of the data, they were submitted to the Genome Analysis ToolKit (GATK). Results: In women, 1788 variants were identified in tumor fragments and 221 variants in plasma; 66 variants were simultaneously detected in tumors and plasma. Conversely, in female dogs, 1430 variants were found in plasma and 695 variants in tumor fragments; 59 variants were simultaneously identified in tumors and plasma. The most frequently mutated genes in the tumor fragments of women were USH2A, ATM, and IGF2R; in female dogs, they were USH2A, BRCA2, and RRM2. Plasma of women showed the most frequent genetic variations in the MAP3K1, BRCA1, and GRB7 genes, whereas plasma from female dogs had variations in the NF1, ERBB2, and KRT17 genes. Mutations in the AKT1, PIK3CA, and BRIP genes were associated with tumor recurrence, with a highly pathogenic variant in PIK3CA being particularly prominent. We also detected a gain-of-function mutation in the GRB7, MAP3K1, and MLH1 genes. Conclusion: Liquid biopsy is useful to identify specific genetic variations at the beginning of BC manifestation and may be accompanied over the entire follow-up period, thereby supporting the clinicians in refining interventions.
Systematic Knowledge Management of Construction Safety Standards Based on Knowledge Graphs: A Case Study in China

Construction safety standards (CSS) have knowledge characteristics, but few studies have introduced knowledge graphs (KG) as a tool into CSS management. In order to improve CSS knowledge management, this paper first analyzed the knowledge structure of 218 standards and obtained three knowledge levels of CSS. Second, a concept layer was designed which consisted of five levels of concepts and eight types of relationships. Third, an entity layer containing 147 entities was constructed via entity identification, attribute extraction and entity extraction. Finally, 177 nodes and 11 types of attributes were collected and the construction of a knowledge graph of construction safety standard (KGCSS) was completed using knowledge storage. Furthermore, we implemented knowledge inference and obtained CSS planning, i.e., the list of standard work plans used to guide the development and revision of CSS. In addition, we conducted CSS knowledge retrieval; a process which supports interrogative input. The construction of KGCSS thus facilitates the analysis, querying, and sharing of safety standards knowledge.
Inhibition of FABP6 Reduces Tumor Cell Invasion and Angiogenesis through the Decrease in MMP-2 and VEGF in Human Glioblastoma Cells

Malignant glioma is one of the most lethal cancers with rapid progression, high recurrence, and poor prognosis in the central nervous system. Fatty acid-binding protein 6 (FABP6) is a bile acid carrier protein that is overexpressed in colorectal cancer. This study aimed to assess the involvement of FABP6 expression in the progression of malignant glioma. Immunohistochemical analysis revealed that FABP6 expression was higher in glioma than in normal brain tissue. After the knockdown of FABP6, a decrease in the migration and invasion abilities of glioma cells was observed. The phosphorylation of the myosin light chain was inhibited, which may be associated with migration ability. Moreover, expression levels of invasion-related proteins, matrix metalloproteinase-2 (MMP-2) and cathepsin B, were reduced. Furthermore, tube formation was inhibited in the human umbilical vein endothelial cells with a decreased concentration of vascular endothelial growth factor (VEGF) in the conditioned medium after the knockdown of FABP6. The phosphorylation of the extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p65 were also decreased after FABP6 reduction. Finally, the bioluminescent images and immunostaining of MMP-2, cluster of differentiation 31 (CD31), and the VEGF receptor 1 (VEGFR1) revealed attenuated tumor progression in the combination of the FABP6-knocked-down and temozolomide (TMZ)-treated group in an orthotopic xenograft mouse tumor model. This is the first study that revealed the impact of FABP6 on the invasion, angiogenesis, and progression of glioma. The results of this study show that FABP6 may be a potential therapeutic target combined with TMZ for malignant gliomas.
Insights into Bone Morphogenetic Protein—(BMP-) Signaling in Ocular Lens Biology and Pathology

Bone morphogenetic proteins (BMPs) are a diverse class of growth factors that belong to the transforming growth factor-beta (TGFβ) superfamily. Although originally discovered to possess osteogenic properties, BMPs have since been identified as critical regulators of many biological processes, including cell-fate determination, cell proliferation, differentiation and morphogenesis, throughout the body. In the ocular lens, BMPs are important in orchestrating fundamental developmental processes such as induction of lens morphogenesis, and specialized differentiation of its fiber cells. Moreover, BMPs have been reported to facilitate regeneration of the lens, as well as abrogate pathological processes such as TGFβ-induced epithelial-mesenchymal transition (EMT) and apoptosis. In this review, we summarize recent insights in this topic and discuss the complexities of BMP-signaling including the role of individual BMP ligands, receptors, extracellular antagonists and cross-talk between canonical and non-canonical BMP-signaling cascades in the lens. By understanding the molecular mechanisms underlying BMP activity, we can advance their potential therapeutic role in cataract prevention and lens regeneration.
The Role of Insulin-like Growth Factor-1 (IGF-1) in the Control of Neuroendocrine Regulation of Growth

In mammals, the neuroendocrine system, which includes the communication between the hypothalamus and the pituitary, plays a major role in controlling body growth and cellular metabolism. GH produced from the pituitary somatotroph is considered the master regulator of somatic development and involved, directly and indirectly, in carbohydrate and lipid metabolism via complex, yet well-defined, signaling pathways. GH production from the pituitary gland is primarily regulated by the counter-regulatory effects of the hypothalamic GHRH and SST hormones. The role of IGF-1 feedback regulation in GH production has been demonstrated by pharmacologic interventions and in genetically modified mouse models. In the present review, we discuss the role of IGF-1 in the regulation of the GH-axis as it controls somatic growth and metabolic homeostasis. We present genetically modified mouse models that maintain the integrity of the GH/GHRH-axis with the single exception of IGF-1 receptor (IGF-1R) deficiency in the hypothalamic GHRH neurons and somatotroph that reveals a novel mechanism controlling adipose tissues physiology and energy expenditure.
Hyperhomocysteinemia: Metabolic Role and Animal Studies with a Focus on Cognitive Performance and Decline—A Review

Disturbances in the one-carbon metabolism are often indicated by altered levels of the endogenous amino acid homocysteine (HCys), which is additionally discussed to causally contribute to diverse pathologies. In the first part of the present review, we profoundly and critically discuss the metabolic role and pathomechanisms of HCys, as well as its potential impact on different human disorders. The use of adequate animal models can aid in unravelling the complex pathological processes underlying the role of hyperhomocysteinemia (HHCys). Therefore, in the second part, we systematically searched PubMed/Medline for animal studies regarding HHCys and focused on the potential impact on cognitive performance and decline. The majority of reviewed studies reported a significant effect of HHCys on the investigated behavioral outcomes. Despite of persistent controversial discussions about equivocal findings, especially in clinical studies, the present evaluation of preclinical evidence indicates a causal link between HHCys and cognition-related- especially dementia-like disorders, and points out the further urge for large-scale, well-designed clinical studies in order to elucidate the normalization of HCys levels as a potential preventative or therapeutic approach in human pathologies.
Inflammatory and Non-Inflammatory Mechanisms Controlling Cirrhosis Development

Simple Summary The liver is continuously exposed to several harmful factors, subsequently activating sophisticated mechanisms set-up in order to repair and regenerate the damaged liver and hence to prevent its failure. When the injury becomes chronic, the regenerative response becomes perpetual and goes awry, leading to cirrhosis with a fatal liver dysfunction. Cirrhosis is a well-known risk factor for hepatocellular carcinoma (HCC), the most common, usually lethal, human primary liver neoplasm with very limited therapeutic options. Considering the pivotal role of immune factors in the development of cirrhosis, here we review and discuss the inflammatory pathways and components implicated in the development of cirrhosis. A better understanding of these circuits would help the design of novel strategies to prevent and treat cirrhosis and HCC, two lethal diseases. Abstract Because the liver is considered to be one of the most important metabolic organs in the body, it is continuously exposed to damaging environmental agents. Upon damage, several complex cellular and molecular mechanisms in charge of liver recovery and regeneration are activated to prevent the failure of the organ. When liver injury becomes chronic, the regenerative response goes awry and impairs the liver function, consequently leading to cirrhosis, a liver disorder that can cause patient death. Cirrhosis has a disrupted liver architecture and zonation, along with the presence of fibrosis and parenchymal nodules, known as regenerative nodules (RNs). Inflammatory cues contribute to the cirrhotic process in response to chronic damaging agents. Cirrhosis can progress to HCC, the most common and one of the most lethal liver cancers with unmet medical needs. Considering the essential role of inflammatory pathways in the development of cirrhosis, further understanding of the relationship between immune cells and the activation of RNs and fibrosis would guide the design of innovative therapeutic strategies to ameliorate the survival of cirrhotic and HCC patients. In this review, we will summarize the inflammatory mechanisms implicated in the development of cirrhosis.
Regulation of Structure and Quality of Dried Noodles by Liquid Pre-Fermentation

Liquid pre-fermentation technology was innovatively applied to the development of dried fermented noodles. The effects of fermentation time (1, 3 and 6 h) and yeast addition (0.2, 0.5 and 1.0 g/100 g of flour) on the quality, microstructure and flavor of dried noodles were also investigated in this study. Conspicuous porous structures and greater thickness of dried noodles were found when the fermentation time was ≤ 3 h and the yeast addition was ≥ 0.5 g/100 g of flour, which contributed to the increase in the breaking strength, cooking time and water absorption. However, when the fermentation time increased to 6 h, finer microporous structures, little change related to thickness and richer flavor levels were detected. Additionally, the total titratable acidity of dried fermented noodles was increased to 3.38–4.43 mL compared with the unfermented noodles (2.15 mL). Weaker gluten network structures caused by long-time fermentation and acidic environment led to lower hardness, chewiness, tensile force and tensile distance of cooked fermented noodles.
Discriminable Multi-Label Attribute Selection for Pre-Course Student Performance Prediction

The university curriculum is a systematic and organic study complex with some immediate associated steps; the initial learning of each semester’s course is crucial, and significantly impacts the learning process of subsequent courses and further studies. However, the low teacher–student ratio makes it difficult for teachers to consistently follow up on the detail-oriented learning situation of individual students. The extant learning early warning system is committed to automatically detecting whether students have potential difficulties—or even the risk of failing, or non-pass reports—before starting the course. Previous related research has the following three problems: first of all, it mainly focused on e-learning platforms and relied on online activity data, which was not suitable for traditional teaching scenarios; secondly, most current methods can only proffer predictions when the course is in progress, or even approaching the end; thirdly, few studies have focused on the feature redundancy in these learning data. Aiming at the traditional classroom teaching scenario, this paper transforms the pre-class student performance prediction problem into a multi-label learning model, and uses the attribute reduction method to scientifically streamline the characteristic information of the courses taken and explore the important relationship between the characteristics of the previously learned courses and the attributes of the courses to be taken, in order to detect high-risk students in each course before the course begins. Extensive experiments were conducted on 10 real-world datasets, and the results proved that the proposed approach achieves better performance than most other advanced methods in multi-label classification evaluation metrics.
Stress Relief Techniques: p38 MAPK Determines the Balance of Cell Cycle and Apoptosis Pathways

Protein signaling networks are formed from diverse and inter-connected cell signaling pathways converging into webs of function and regulation. These signaling pathways both receive and conduct molecular messages, often by a series of post-translation modifications such as phosphorylation or through protein–protein interactions via intrinsic motifs. The mitogen activated protein kinases (MAPKs) are components of kinase cascades that transmit signals through phosphorylation. There are several MAPK subfamilies, and one subfamily is the stress-activated protein kinases, which in mammals is the p38 family. The p38 enzymes mediate a variety of cellular outcomes including DNA repair, cell survival/cell fate decisions, and cell cycle arrest. The cell cycle is itself a signaling system that precisely controls DNA replication, chromosome segregation, and cellular division. Another indispensable cell function influenced by the p38 stress response is programmed cell death (apoptosis). As the regulators of cell survival, the BCL2 family of proteins and their dynamics are exquisitely sensitive to cell stress. The BCL2 family forms a protein–protein interaction network divided into anti-apoptotic and pro-apoptotic members, and the balance of binding between these two sides determines cell survival. Here, we discuss the intersections among the p38 MAPK, cell cycle, and apoptosis signaling pathways.
Modulation of Functional Connectivity in Response to Mirror Visual Feedback in Stroke Survivors: An MEG Study

Background. Several brain regions are activated in response to mirror visual feedback (MVF). However, less is known about how these brain areas and their connectivity are modulated in stroke patients. This study aimed to explore the effects of MVF on brain functional connectivity in stroke patients. Materials and Methods. We enrolled 15 stroke patients who executed Bilateral-No mirror, Bilateral-Mirror, and Unilateral-Mirror conditions. The coherence values among five brain regions of interest in four different frequency bands were calculated from magnetoencephalographic signals. We examined the differences in functional connectivity of each two brain areas between the Bilateral-No mirror and Bilateral-Mirror conditions and between the Bilateral-Mirror and Unilateral-Mirror conditions. Results. The functional connectivity analyses revealed significantly stronger connectivity between the posterior cingulate cortex and primary motor cortex in the beta band (adjusted p = 0.04) and possibly stronger connectivity between the precuneus and primary visual cortex in the theta band (adjusted p = 0.08) in the Bilateral-Mirror condition than those in the Bilateral-No mirror condition. However, the comparisons between the Bilateral-Mirror and Unilateral-Mirror conditions revealed no significant differences in cortical coherence in all frequency bands. Conclusions. Providing MVF to stroke patients may modulate the lesioned primary motor cortex through visuospatial and attentional cortical networks.
Silver Nanoparticles Biosynthesized with Spruce Bark Extract—A Molecular Aggregate with Antifungal Activity against Candida Species

Due to their high content of biomolecules, combined with silver’s well known antimicrobial potential, silver nanoparticles biosynthesized using spruce bark (AgNP SBEs) demonstrate antibacterial and antioxidant activity, making them a versatile option for developing new antimicrobial agents that might be used for medical treatment or as adjuvants for the classical agents. This study aims to analyze if silver nanoparticles (AgNPs) mediated by spruce bark extract (SBE) and silver salts (AgNP SBE Acetate, AgNP SBE Nitrate) presents antifungal activity against five different Candida spp. , synergistic activity with fluconazole, and if they interact with some virulence factors of C. albicans. AgNP SBEs presented MICs (minimum inhibitory concentrations) for all the five tested Candida spp. AgNP SBEs inhibited the growth of C. parapsilosis, C. krusei, and C. guilliermondii, exerted synergistic activity with fluconazole for C. parapsilosis and C. guilliermondii, and inhibited biofilm production for C. albicans, C. auris, and C. guilliermondii. MICs of AgNP SBE Acetate significantly inhibited the production of germ tubes of C. albicans. The expression of C. albicans SAP2 gene was down-regulated by the short-time treatment with MICs of AgNP SBE Acetate, while ALS3 and HSP70 genes were up-regulated by the AgNPs MICs. These results emphasize the potential of using the AgNP SBEs as treatments/adjuvants options, not only against the redundant C. albicans but also for the non-albicans Candida species (which are not as frequently involved in human pathologies, but, sometimes, can be more aggressive).
Roles of Crosstalk between Astrocytes and Microglia in Triggering Neuroinflammation and Brain Edema Formation in 1,2-Dichloroethane-Intoxicated Mice

We have previously reported that the activation of astrocytes and microglia may lead to the overproduction of proinflammatory mediators, which could induce neuroinflammation and cause brain edema in 1,2-dichloroethane (1,2-DCE)-intoxicated mice. In this research, we further hypothesized that astrocyte–microglia crosstalk might trigger neuroinflammation and contribute to brain edema in 1,2-DCE-intoxicated mice. The present research revealed, for the first time, that subacute intoxication with 1,2-DCE might provoke the proinflammatory polarization of microglia, and pretreatment with minocycline, a specific inhibitor of microglial activation, may attenuate the enhanced protein levels of ionized calcium-binding adapter molecule1 (Iba-1), cluster of differentiation 11b (CD11b), glial fibrillary acidic protein (GFAP), soluble calcium-binding protein 100B (S100B), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), inducible nitric oxide synthase (iNOS), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), matrix metalloproteinase-9 (MMP-9), Toll-like receptor 4 (TLR4), MyD88, and p-p65, and ameliorate the suppressed protein expression levels of occludin and claudin 5; we also observed changes in water content and made pathological observations on edema in the brains of 1,2-DCE-intoxicated mice. Moreover, pretreatment with fluorocitrate, an inhibitor of reactive astrocytes, could also reverse the alteration in protein expression levels of GFAP, S100B, Iba-1, CD11b, TNF-α, IL-6, iNOS, VCAM-1, ICAM-1, MMP-9, occludin, and claudin 5 in the brain of 1,2-DCE intoxicated mice. Furthermore, pretreatment with melatonin, a well-known anti-inflammatory drug, could also attenuate the above-mentioned changes in the brains of 1,2-DCE-intoxicated mice. Altogether, the findings from this research indicated that microglial activation might play an important role in triggering neuroinflammation, and hence may contribute to brain edema formation; additionally, the findings suggested that molecular crosstalk between reactive astrocytes and activated microglia may amplify the neuroinflammatory reaction, which could induce secondary brain injury in 1,2-DCE-intoxicated mice.