Miracle-dz/UniFAR-FTUs huggingface dataset:
Dexamethasone Inhibits Heparan Sulfate Biosynthetic System and Decreases Heparan Sulfate Content in Orthotopic Glioblastoma Tumors in Mice

Glioblastoma (GB) is an aggressive cancer with a high probability of recurrence, despite active chemoradiotherapy with temozolomide (TMZ) and dexamethasone (DXM). These systemic drugs affect the glycosylated components of brain tissue involved in GB development; however, their effects on heparan sulfate (HS) remain unknown. Here, we used an animal model of GB relapse in which SCID mice first received TMZ and/or DXM (simulating postoperative treatment) with a subsequent inoculation of U87 human GB cells. Control, peritumor and U87 xenograft tissues were investigated for HS content, HS biosynthetic system and glucocorticoid receptor (GR, Nr3c1). In normal and peritumor brain tissues, TMZ/DXM administration decreased HS content (5–6-fold) but did not affect HS biosynthetic system or GR expression. However, the xenograft GB tumors grown in the pre-treated animals demonstrated a number of molecular changes, despite the fact that they were not directly exposed to TMZ/DXM. The tumors from DXM pre-treated animals possessed decreased HS content (1.5–2-fold), the inhibition of HS biosynthetic system mainly due to the -3–3.5-fold down-regulation of N-deacetylase/N-sulfotransferases (Ndst1 and Ndst2) and sulfatase 2 (Sulf2) expression and a tendency toward a decreased expression of the GRalpha but not the GRbeta isoform. The GRalpha expression levels in tumors from DXM or TMZ pre-treated mice were positively correlated with the expression of a number of HS biosynthesis-involved genes (Ext1/2, Ndst1/2, Glce, Hs2st1, Hs6st1/2), unlike tumors that have grown in intact SCID mice. The obtained data show that DXM affects HS content in mouse brain tissues, and GB xenografts grown in DXM pre-treated animals demonstrate attenuated HS biosynthesis and decreased HS content.
Data on New Intermediate and Accidental Hosts Naturally Infected with Angiostrongylus cantonensis in La Gomera and Gran Canaria (Canary Islands, Spain)

Simple Summary The rat lungworm, Angiostrongylus cantonensis, is the world’s leading cause of eosinophilic meningitis in humans. It is an emerging zoonotic parasite endemic to Asia and the Pacific Islands that has spread to all continents except Antarctica. In the Canary Islands, its presence was first detected in 2010 on the island of Tenerife. Numerous studies demonstrated the high capacity of A. cantonensis to colonize new areas, especially its ability to parasitize a wide range of animals. Due to the similarity of the ecosystems that we can find between the islands that make up the Canary Archipelago and the great diversity of species of both vertebrates and terrestrial gastropods, the objective of this study was to analyze several species as possible hosts of A. cantonensis on other islands in the Canary Islands, with the use of molecular tools. The present study confirmed the presence of A. cantonensis in two mammalian species, Mus musculus and Felis catus, and in four terrestrial gastropod species, Limacus flavus, Milax gagates, Insulivitrina emmersoni, and Insulivitrina oromii. The presence of A. cantonensis implies a possible risk to humans and other animals, which justifies the need for control measures to control the possible risk of infection and, thus, prevent public health and veterinary problems. Abstract Angiostrongylus cantonensis is a metastrongyloid nematode and the etiologic agent of angiostrongyliasis, a disease characterized by eosinophilic meningitis. This emerging zoonotic parasite has undergone great expansion, including in some regions of Europe and America. In the Canary Islands, the parasite was first discovered parasitizing Rattus rattus on the island of Tenerife in 2010. To date, the distribution of this parasite in the Canary Islands has been restricted to the northern zone and the main cities of Tenerife. Using molecular tools for the sentinel species present in the Canary Islands, this study confirmed the presence of the nematode on two other islands in the Canary Archipelago: La Gomera and Gran Canaria. Furthermore, this emerging parasite was detected, besides in the common definitive host R. rattus, in wild Mus musculus and Felis catus and in four terrestrial gastropod species, Limacus flavus, Milax gagates, Insulivitrina emmersoni, and Insulivitrina oromii, two of them endemic to La Gomera, for the first time, increasing the number of non-definitive host species. This study reinforces the expansion character of A. cantonensis and highlights the importance of knowledge about sentinel species for identifying new transmission locations that help prevent and control the transmission of the parasite and, thus, prevent public health problems.
Deep Learning- and Expert Knowledge-Based Feature Extraction and Performance Evaluation in Breast Histopathology Images

Simple Summary Breast cancer is one of the leading causes of cancer death among women. Developing machine learning-based diagnosis models receives great attention from researchers and scientists using histopathology images. Deep learning (DL) algorithms automatically extract features from raw data through convolutional operations. The generalization of the DL models’ results relies on large datasets, although they eliminate the expert knowledge in the feature extraction stage. This work aimed to compare the performance of the features extracted via deep learning and a knowledge-based approach in breast cancer detection from histopathology images. Abstract Cancer develops when a single or a group of cells grows and spreads uncontrollably. Histopathology images are used in cancer diagnosis since they show tissue and cell structures under a microscope. Knowledge-based and deep learning-based computer-aided detection is an ongoing research field in cancer diagnosis using histopathology images. Feature extraction is vital in both approaches since the feature set is fed to a classifier and determines the performance. This paper evaluates three feature extraction methods and their performance in breast cancer diagnosis. Features are extracted by (1) a Convolutional Neural Network, (2) a transfer learning architecture VGG16, and (3) a knowledge-based system. The feature sets are tested by seven classifiers, including Neural Network (64 units), Random Forest, Multilayer Perceptron, Decision Tree, Support Vector Machines, K-Nearest Neighbors, and Narrow Neural Network (10 units) on the BreakHis 400× image dataset. The CNN achieved up to 85% for the Neural Network and Random Forest, the VGG16 method achieved up to 86% for the Neural Network, and the knowledge-based features achieved up to 98% for Neural Network, Random Forest, Multilayer Perceptron classifiers.
Could Oxidative Stress Play a Role in the Development and Clinical Management of Differentiated Thyroid Cancer?

Simple Summary Increased oxidative stress (OS) has been implicated as a relevant risk factor for cancer development and progression. The incidence of differentiated thyroid cancer (DTC) has risen in several populations globally over the last few decades, accounting for approximately 1% of all cancer cases. Patients with DTC diagnosis have been characterized by an increased OS status, which is associated with a poorer prognosis. Therefore, assessing OS status could potentially be considered a useful tool in DTC clinical management. This measurement could be particularly valuable in personalizing treatment protocols and determining new potential medical targets. The purpose of this article is to evaluate research that examines the influence of OS on the progression of DTC and investigate the feasibility of utilizing OS measurements in DTC risk assessment. Gaining a comprehensive understanding of the correlation between carcinogenesis and OS, specifically in the DTC cases, can facilitate the development of novel therapeutic strategies. Abstract Increased oxidative stress (OS) has been implicated as a relevant risk factor for cancer progression. Furthermore, patients diagnosed with differentiated thyroid cancer (DTC) have been characterized by an increased OS status. Therefore, assessing OS status could potentially be considered a useful tool in DTC clinical management. This measurement could be particularly valuable in personalizing treatment protocols and determining new potential medical targets to improve commonly used therapies. A literature review was conducted to gather new information on DTC clinical management, with a particular focus on evaluating the clinical utility of OS. These meta-analyses concentrate on novel approaches that employ the measurement of oxidative-antioxidant status, which could represent the most promising area for implementing clinical management.
Drought Eliminates the Difference in Root Trait Plasticity and Mycorrhizal Responsiveness of Two Semiarid Grassland Species with Contrasting Root System

Root traits and arbuscular mycorrhizal (AM) fungi are important in determining the access of plants to soil resources. However, whether plants with different root systems (i.e., taproot vs. fibrous-root) exhibit different root trait plasticity and mycorrhizal responsiveness under drought remains largely unexplored. Tap-rooted Lespedeza davurica and fibrous-rooted Stipa bungeana were grown in monocultures in sterilized and live soils, followed by a drought treatment. Biomass, root traits, root colonization by AM fungi, and nutrient availability were evaluated. Drought decreased biomass and root diameter but increased the root:shoot ratio (RSR), specific root length (SRL), soil NO3−-N, and available P for the two species. Under control and drought conditions, soil sterilization significantly increased the RSR, SRL, and soil NO3−-N for L. davurica, but this only occurs under drought condition for S. bungeana. Soil sterilization significantly reduced AM fungal root colonization of both species, but drought significantly increased it in live soil. In water-abundant conditions, tap-rooted L. davurica may depend more on AM fungi than fibrous-rooted S. bungeana; however, under drought conditions, AM fungi are of equal importance in favoring both plant species to forage soil resources. These findings provide new insights for understanding the resource utilization strategies under climate change.
P2X7 Receptor and Extracellular Vesicle Release

Extensive evidence indicates that the activation of the P2X7 receptor (P2X7R), an ATP-gated ion channel highly expressed in immune and brain cells, is strictly associated with the release of extracellular vesicles. Through this process, P2X7R-expressing cells regulate non-classical protein secretion and transfer bioactive components to other cells, including misfolded proteins, participating in inflammatory and neurodegenerative diseases. In this review, we summarize and discuss the studies addressing the impact of P2X7R activation on extracellular vesicle release and their activities.
Adolescent Cyberbullies’ Attributions: Longitudinal Linkages to Cyberbullying Perpetration

The aim of the present study was to examine cyberbullies’ attributions pertaining to their perpetration of cyberbullying, and how such attributions relate to their cyberbullying behaviors six months later. Participants were 216 adolescents (M = 13.46, SD = 0.62 years; 55% female) from the suburbs of a large Midwestern city in the United States. They were interviewed face-to-face in the fall of 2018 concerning why they acted in negative ways toward peers online or through text messages. They also answered questionnaires regarding how often they perpetrated face-to-face bullying and cyberbullying during the fall of 2018 and spring of 2019. The attributions of revenge, convenience, anger, and anonymity each predicted cyberbullying at the second time point while controlling for face-to-face bullying perpetration. Results from this study provide important information to the literature regarding cyberbullies’ attributions for perpetrating cyberbullying, and how such attributions predict future cyberbullying perpetration. These findings are important for the development of antibullying programs that might aim to change adolescents’ attributions for cyberbullying perpetration to reduce continued engagement in these behaviors.
Estradiol Protects Female ApoE KO Mice against Western-Diet-Induced Non-Alcoholic Steatohepatitis

The prevalence of non-alcoholic fatty liver disease (NAFLD) and its severe form, non-alcoholic steatohepatitis (NASH), is higher in men than in women of reproductive age, and postmenopausal women are especially susceptible to developing the disease. Aim: we evaluated if female apolipoprotein E (ApoE) KO mice were protected against Western-diet (WD)-induced NASH. Methods: Female ovariectomized (OVX) ApoE KO mice or sham-operated (SHAM) mice were fed either a WD or a regular chow (RC) for 7 weeks. Additionally, OVX mice fed a WD were treated with either estradiol (OVX + E2) or vehicle (OVX). Results: Whole-body fat, plasma glucose, and plasma insulin were increased and associated with increased glucose intolerance in OVX mice fed a WD (OVX + WD). Plasma and hepatic triglycerides, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) hepatic enzymes were also increased in the plasma of OVX + WD group, which was associated with hepatic fibrosis and inflammation. Estradiol replacement in OVX mice reduced body weight, body fat, glycemia, and plasma insulin associated with reduced glucose intolerance. Treatment also reduced hepatic triglycerides, ALT, AST, hepatic fibrosis, and inflammation in OVX mice. Conclusions: These data support the hypothesis that estradiol protects OVX ApoE KO mice from NASH and glucose intolerance.
The Multi-Faceted Nature of Renalase for Mitochondrial Dysfunction Improvement in Cardiac Disease

The cellular mechanisms and signaling network that guide the cardiac disease pathophysiology are inextricably intertwined, which explains the current scarcity of effective therapy and to date remains the greatest challenge in state-of-the-art cardiovascular medicine. Accordingly, a novel concept has emerged in which cardiomyocytes are the centerpiece of therapeutic targeting, with dysregulated mitochondria as a critical point of intervention. Mitochondrial dysfunction pluralism seeks a multi-faceted molecule, such as renalase, to simultaneously combat the pathophysiologic heterogeneity of mitochondria-induced cardiomyocyte injury. This review provides some original perspectives and, for the first time, discusses the functionality spectrum of renalase for mitochondrial dysfunction improvement within cardiac disease, including its ability to preserve mitochondrial integrity and dynamics by suppressing mitochondrial ΔΨm collapse; overall ATP content amelioration; a rise of mtDNA copy numbers; upregulation of mitochondrial genes involved in oxidative phosphorylation and cellular vitality promotion; mitochondrial fission inhibition; NAD+ supplementation; sirtuin upregulation; and anti-oxidant, anti-apoptotic, and anti-inflammatory traits. If verified that renalase, due to its multi-faceted nature, behaves like the “guardian of mitochondria” by thwarting pernicious mitochondrial dysfunction effects and exerting therapeutic potential to target mitochondrial abnormalities in failing hearts, it may provide large-scale benefits for cardiac disease patients, regardless of the underlying causes.
Kinematic Distances of SNRs W44 and 3C 391

Abstract We extracted the neutral hydrogen absorption spectra of supernova remnants W44 (G34.7-0.4) and 3C 391 (G31.9+0.0) from the VLA Galactic Plane Survey data. The revised distance of W41 is about 3.3 kpc replacing the previous 3.0 kpc. Further, we confined the distance of G31.9+0.0 to about 7.2 kpc due to its interaction with its surrounding molecular clouds.
Mycobacterium avium subsp. paratuberculosis Candidate Vaccine Strains Are Pro-apoptotic in RAW 264.7 Murine Macrophages

Mycobacterium avium subsp. paratuberculosis (MAP) is the etiological agent of Johne’s disease, a severe gastroenteritis of ruminants. This study developed a model cell culture system to rapidly screen MAP mutants with vaccine potential for apoptosis. Two wild-type strains, a transposon mutant, and two deletion mutant MAP strains (MOI of 10 with 1.2 × 106 CFU) were tested in murine RAW 264.7 macrophages to determine if they induce apoptosis and/or necrosis. Both deletion mutants were previously shown to be attenuated and immunogenic in primary bovine macrophages. All strains had similar growth rates, but cell morphology indicated that both deletion mutants were elongated with cell wall bulging. Cell death kinetics were followed by a real-time cellular assay to measure luminescence (apoptosis) and fluorescence (necrosis). A 6 h infection period was the appropriate time to assess apoptosis that was followed by secondary necrosis. Apoptosis was also quantified via DAPI-stained nuclear morphology and validated via flow cytometry. The combined analysis confirmed the hypothesis that candidate vaccine deletion mutants are pro-apoptotic in RAW 264.7 cells. In conclusion, the increased apoptosis seen in the deletion mutants correlates with the attenuated phenotype and immunogenicity observed in bovine macrophages, a property associated with good vaccine candidates.
Solving Linear Operator Equations

Let be a complex Banach space and the algebra of bounded operators on . M. Rosenblum's theorem [13; 12] (also discovered by M. G. Kreĭn, cf. [9]) states that (if A, B are fixed bounded operators) the spectrum of the operator on defined by = AX – XB is contained in σ (A) – σ(B) = {α – β : α ∊ σ(A), β ∊ σ(B)}. In particular, the condition σ(A) ∩ σ(B) = Ø implies that for each Y ∊ there is a unique X ∊ such that AX – XB = Y. This does not completely settle the question of solvability of the equation AX – XB = Y: for example, if A is the backward unilateral shift and B = 0, then the equation has a solution (for any Y) even though σ(B) ⊆ σ(A).
Relationship between CDX2 rs11568820 and EcoRV rs4516035 polymorphisms on the vitamin D receptor gene with susceptibility to different SARS‐CoV‐2 variants

Several studies have revealed that vitamin D deficiency is linked to an increased risk of developing coronavirus disease 19 (COVID‐19). In individuals with the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infections, vitamin D receptor activation is required to decrease acute respiratory distress syndrome. The purpose of this study was to examine the genotypic distribution and allelic frequencies of CDX2 rs11568820 and EcoRV rs4516035 polymorphisms in COVID‐19 patients with various SARS‐CoV‐2 variants. For genotyping of CDX2 rs11568820 and EcoRV rs4516035 polymorphisms, we used the polymerase chain reaction‐restriction fragment length polymorphism technique in 1734 and 1450 recovered and deceased patients, respectively. The results indicated the rate of COVID‐19 mortality was associated with CDX2 rs11568820 AA and GA genotypes in the Delta variant and with CDX2 rs11568820 AA in the Omicron BA.5 variant, while no association was shown in the Alpha variant. Therefore, the rate of COVID‐19 mortality was associated with EcoRV rs4516035 TC and CC genotypes in the Delta variant, while no association was shown in the Alpha and Omicron BA.5 variants. According to our analysis, the T‐G haplotype was more common in all SARS‐CoV‐2 variants. The C‐A haplotype was associated with COVID‐19 mortality in the Delta and Omicron BA.5 variants, and the T‐A haplotype was related to the Alpha variant. In conclusion, the genotype frequencies of the CDX2 rs11568820 and EcoRV rs4516035 polymorphisms between SARS‐CoV‐2 variants were significantly different between the deceased patients and recovered patients. However, more studies should be done to confirm the results.
Linalool-Incorporated Synergistically Engineered Modified Liposomal Nanocarriers for Enhanced Transungual Delivery of Terbinafine against Onychomycosis

This work investigates the synthesis of linalool-containing invasomes for terbinafine (TBF-IN) in order to increase the solubility, bioavailability, and nail permeability of terbinafine (TBF) for transungual administration. TBF-IN was created utilising the thin-film hydration technique, and with the Box–Behnken design (BBD), optimisation was carried out. TBF-INopt were investigated for vesicle size, zeta potential, PDI (Polydispersity index), entrapment efficiency (EE) and in vitro TBF release. In addition, nail permeation analysis, TEM (transmission electron microscopy), and CLSM (confocal scanning laser microscopy) were performed for further evaluation. The TBF-INopt exhibited spherical as well as sealed vesicles with a considerably small size of 146.3 nm, an EE of 74.23 per cent, a PDI of 0.1612, and an in vitro release of 85.32 per cent. The CLSM investigation revealed that the new formulation had better TBF nail penetration than the TBF suspension gel. The antifungal investigation demonstrated that the TBF-IN gel has superior antifungal activity against Trichophyton rubrum and Candida albicans compared to the commercially available terbinafine gel. In addition, an investigation of skin irritation using Wistar albino rats indicates that the TBF-IN formulation is safe for topical treatment. This study confirmed that the invasomal vesicle formulation is an effective vehicle for the transungual delivery of TBF for the treatment of onychomycosis.
Association of ADH1B rs1229984, ADH1C rs698, and ALDH2 rs671 with Alcohol abuse and Alcoholic Cirrhosis in People Living in Northeast Vietnam

Objective: Alcohol abuse can cause developing cirrhosis, even liver cancer. Several single nucleotide polymorphisms (SNPs) of ADH1B, ADH1C, and ALDH2 genes have been reported to be associated with alcohol abuse and alcoholic cirrhosis (ALC). This study investigated the association between three SNPs of ADH1B rs1229984, ADH1C rs698, and ALDH2 rs671 with alcohol abuse and ALC in people living in the Northeast region of Vietnam. Methods: 306 male participants were recruited including 206 alcoholics (106 ALC, 100 without ALC) and 100 healthy non-alcoholics. Clinical characteristics were collected by clinicians. Genotypes were identified by Sanger sequencing. Chi-Square (χ2) and Fisher-exact tests were used to assess the differences in age and clinical characteristics, Child-Pugh score, frequencies of alleles and genotypes. Result: Our data showed that the frequency of ALDH2*1 was significantly higher in alcoholics (88.59%) and ALC groups (93.40%) than that of healthy non-alcoholics (78.50%) with p=0.0009 and non-ALC group (83.50%) with p=0.002, respectively. We detected opposite results when examined ALDH2*2. Frequency of combined genotypes with high acetaldehyde accumulation were significantly lower in alcoholics and ALC group than those of control groups with p=0.005 and p=0.008, respectively. Meanwhile, the proportion of combined genotypes with non-acetaldehyde accumulation were significantly two times higher in the ALC group (19.98%) than those of the non-ALC group (8%) with p=0.035. These combined genotypes showed a decreasing trend in the Child-Pugh score from likely phenotype causing risk for non-acetaldehyde accumulation to high acetaldehyde accumulation. Conclusion: The ALDH2*1 allele was found as a risk factor for alcohol abuse and ALC, and combined genotypes of ADH1B rs1229984, ADH1C rs698, and ALDH2 rs671 with non-acetaldehyde accumulation increase ALC risk. In contrast, ALDH2*2 and the genotype combinations related to high acetaldehyde accumulation were protective factors against alcohol abuse and ALC.