Miracle-dz/UniFAR-FTUs huggingface dataset:
Intrinsic Subtypes and Androgen Receptor Gene Expression in Primary Breast Cancer. A Meta-Analysis

Simple Summary Breast cancer (BC) is the second largest cause of death for cancer in women worldwide. Different studies have shown that the androgen receptor (AR), a cytoplasmic ligand-dependent transcription factor, may play a role as a marker of BC biology. We aimed to assess the clinical significance of AR gene expression in BC by meta-analysis of large-scale microarray transcriptomic datasets. Our findings suggest that high mRNA levels of AR have the potential to be a promising non-invasive prognostic biomarker for the identification of the less aggressive BC subtypes. Abstract The androgen receptor (AR) is frequently expressed in breast cancer (BC), but its association with clinical and biological parameters of BC patients remains unclear. Here, we investigated the association of AR gene expression according to intrinsic BC subtypes by meta-analysis of large-scale microarray transcriptomic datasets. Sixty-two datasets including 10315 BC patients were used in the meta-analyses. Interestingly, AR mRNA level is significantly increased in patients categorized with less aggressive intrinsic molecular subtypes including, Luminal A compared to Basal-like (standardized mean difference, SMD: 2.12; 95% confidence interval, CI: 1.88 to 2.35; p < 0.001) or when comparing Luminal B to Basal-like (SMD: 1.53; CI: 1.33 to 1.72; p < 0.001). The same trend was observed when analyses were performed using immunohistochemistry-based surrogate subtypes. Consistently, the AR mRNA expression was higher in patients with low histological grade (p < 0.001). Furthermore, our data revealed higher levels of AR mRNA in BC patients expressing either estrogen or progesterone receptors (p < 0.001). Together, our findings indicate that high mRNA levels of AR are associated with BC subgroups with the less aggressive clinical features.
Modeling and Characterization of Complex Concentrated Alloys with Reduced Content of Critical Raw Materials

The continuous development of society has increased the demand for critical raw materials (CRMs) by using them in different industrial applications. Since 2010, the European Commission has compiled a list of CRMs and potential consumption scenarios with significant economic and environmental impacts. Various efforts were made to reduce or replace the CRM content used in the obtaining process of high-performance materials. Complex concentrated alloys (CCAs) are an innovative solution due to their multitude of attractive characteristics, which make them suitable to be used in a wide range of industrial applications. In order to demonstrate their efficiency in use, materials should have improved recyclability, good mechanical or biocompatible properties, and/or oxidation resistance, according to their destination. In order to predict the formation of solid solutions in CCAs and provide the optimal compositions, thermodynamic and kinetic simulations were performed. The selected compositions were formed in an induction furnace and then structurally characterized with different techniques. The empirical results indicate that the obtained CCAs are suitable to be used in advanced applications, providing original contributions, both in terms of scientific and technological fields, which can open new perspectives for the selection, design, and development of new materials with reduced CRM contents.
Protein Kinase A Detection in Human Urine Samples

Actively involved in tumor maintenance, cAMP-dependent protein kinase A (PKA) has been proposed as a putative biomarker in cancer. Recently, an active PKA form has been identified in human sera and PKA autoantibodies have been detected in cancer patients. However, their serum functions, as well as diagnostic significance, remain largely unknown. Although several PKA detection assays have been developed, none refer to a laboratory diagnostic procedure. Among these, ELISA and Western blotting (WB) assays have been employed in PKA detection. Since, to the best of our knowledge, there are no data showing its presence in human urine samples, herein, we explore the possibility of PKA’s existence in this biological specimen. Interestingly, among the 30 screened urines by quantitative sandwich ELISA, we recognized detectable PKA levels in 5 different samples, and of those two exhibited a considerable high concentration. To corroborate these results, we also evaluated PKA’s presence in both positive and negative ELISA urines by WB. Remarkably, immunoblotting analysis confirmed PKA’s existence in certain, but not in all, human urine specimens. Despite being quite preliminary, these findings firstly identify PKA in urine samples and provide evidence for its potential clinic usage as a diagnostic analyte in laboratory medicine.
In Vitro and In Vivo Evaluation of Oral Controlled Release Formulation of BCS Class I Drug Using Polymer Matrix System

Diltiazem hydrochloride is a calcium channel blocker, which belongs to the family of benzothiazepines. It is commonly used to treat hypertension and atrial fibrillation. Even though the drug has high solubility, its high permeability and rapid metabolism in the liver can limit the bioavailability and increase the dose frequencies for up to four times per day. This study focused on a polymer matrix system not only to control the drug release but also to prolong the duration of bioavailability. The polymer matrices were prepared using different ratios of poloxamer-188, hydroxypropyl methylcellulose, and stearyl alcohol. In vitro and in vivo assessments took place using 24 rabbits and the results were compared to commercially available product Tildiem® (60 mg tablet) as reference. Overall, the rate of drug release was sustained with the gradual increase of poloxamer-188 incorporated with hydroxypropyl methylcellulose and stearyl alcohol in the matrix system, achieving a maximum release period of 10 h. The oral bioavailability and pharmacokinetic parameters of diltiazem hydrochloride incorporated in polymer matrix system were similar to commercial reference Tildiem®. In conclusion, the combination of polymers can have a substantial effect on controlling and prolonging the drug release pattern. The outcomes showed that poloxamer-188 combined with hydroxypropyl methylcellulose and stearyl alcohol is a powerful matrix system for controlling release of diltiazem hydrochloride.
Ab Initio Quantum-Mechanical Predictions of Semiconducting Photocathode Materials

Ab initio Quantum-Mechanical methods are well-established tools for material characterization and discovery in many technological areas. Recently, state-of-the-art approaches based on density-functional theory and many-body perturbation theory were successfully applied to semiconducting alkali antimonides and tellurides, which are currently employed as photocathodes in particle accelerator facilities. The results of these studies have unveiled the potential of ab initio methods to complement experimental and technical efforts for the development of new, more efficient materials for vacuum electron sources. Concomitantly, these findings have revealed the need for theory to go beyond the status quo in order to face the challenges of modeling such complex systems and their properties in operando conditions. In this review, we summarize recent progress in the application of ab initio many-body methods to investigate photocathode materials, analyzing the merits and the limitations of the standard approaches with respect to the confronted scientific questions. In particular, we emphasize the necessary trade-off between computational accuracy and feasibility that is intrinsic to these studies, and propose possible routes to optimize it. We finally discuss novel schemes for computationally-aided material discovery that are suitable for the development of ultra-bright electron sources toward the incoming era of artificial intelligence.
Surface-Functionalized Separator for Stable and Reliable Lithium Metal Batteries: A Review

Metallic Li has caught the attention of researchers studying future anodes for next-generation batteries, owing to its attractive properties: high theoretical capacity, highly negative standard potential, and very low density. However, inevitable issues, such as inhomogeneous Li deposition/dissolution and poor Coulombic efficiency, hinder the pragmatic use of Li anodes for commercial rechargeable batteries. As one of viable strategies, the surface functionalization of polymer separators has recently drawn significant attention from industries and academics to tackle the inherent issues of metallic Li anodes. In this article, separator-coating materials are classified into five or six categories to give a general guideline for fabricating functional separators compatible with post-lithium-ion batteries. The overall research trends and outlook for surface-functionalized separators are reviewed.
Diagnostic Strategies for Thyroid Nodules Based on Ultrasonographic Findings in Japan

Simple Summary In recent years, the incidence of thyroid cancer has been increasing worldwide, mainly due to the widespread use of imaging examination methods, such as ultrasonography. In Japan, the risk of overdiagnosis due to the use of diagnostic imaging has been discussed since the 1990s, and measures have been taken to reduce the risk of overdiagnosis and overtreatment by establishing criteria for the implementation of fine needle aspiration cytology and non-surgical follow-up. This article outlines the diagnostic criteria and management guidelines in Japan in comparison with those published in other countries. Abstract In recent years, the incidence of thyroid cancer has been increasing worldwide, which is believed to be mainly due to the widespread use of imaging examinations, such as ultrasonography. In this context, ultrasonography has become increasingly important because it can evaluate not only the presence or absence of nodules, but also the detailed characteristics of the nodule, making it possible to diagnose benign or malignant nodules before cytology is performed. In Japan, the third edition of the sonographic diagnostic criteria for thyroid nodules is currently widely used, and its content is similar to that of recent meta-analyses and guidelines from medical societies in other countries. In addition, since overdiagnosis of very-low-risk thyroid cancer has recently become an issue, criteria for the implementation of fine needle aspiration cytology (FNAC) have been published by various countries. The Japan Society of Breast and Thyroid Sonology provides guidelines for FNAC implementation for solid and cystic nodules. In the United States, the ATA, NCCA, and ACR have published guidelines, whereas in Europe, the ESMO and ETA have done the same. All of these guidelines used to classify risk are based on nodule size and sonographic findings. This article outlines the diagnostic criteria and management guidelines in Japan in comparison with those published in other countries. Case studies using actual images were also performed to examine the differences in the FNAC guidelines.
Vitamin D Incorporation in Foods: Formulation Strategies, Stability, and Bioaccessibility as Affected by the Food Matrix

Inadequate intake of vitamin D is a global health issue related to severe diseases, mainly involving subjects with dark skin pigmentation, patients affected by malnutrition, malabsorption syndromes, or obesity, and elderly people. Some foods fortified with vitamin D have been tested in vivo, but fortification strategies with a global outreach are still lacking. This review is focused on food fortification with vitamin D, with the aim to collect information on (a) formulation strategies; (b) stability during processing and storage; and (c) in vitro bioaccessibility. Approaches to add vitamin D to various foods were analyzed, including the use of free vitamin D, vitamin D loaded in simple and double nanoemulsions, liposomes, casein micelles, and protein nanocapsules. Numerous studies were reviewed to elucidate the impact of food technologies on vitamin D’s stability, and mechanisms that lead to degradation were identified—namely, acid-catalyzed isomerization, radical-induced oxidation, and photo-oxidation. There is, however, a lack of kinetic data that allow for the prediction of vitamin D’s stability under industrial processing conditions. The roles that lipids, proteins, fibers, and antioxidants play in vitamin bioaccessibility have been clarified in various studies, while future needs include the design of specific food matrices that simultaneously achieve a balance between the long-term stability, bioaccessibility and, ultimately, in vivo functionality of vitamin D.
Anti-Oxidative and Immune Regulatory Responses of THP-1 and PBMC to Pulsed EMF Are Field-Strength Dependent

Innate immune cells react to electromagnetic fields (EMF) by generating reactive oxygen species (ROS), crucial intracellular messengers. Discrepancies in applied parameters of EMF studies, e.g., flux densities, complicate direct comparison of downstream anti-oxidative responses and immune regulatory signaling. We therefore compared the impact of different EMF flux densities in human leukemic THP1 cells and peripheral blood mononuclear cells (PBMC) of healthy donors to additionally consider a potential disparate receptivity based on medical origin. ROS levels increased in THP1 cells stimulated with lipopolysaccharide (LPS) after one hour of EMF exposure. Moreover, weak EMF mitigated the depletion of the reducing agent NAD(P)H in THP1. Neither of these effects occurred in PBMC. Landscaping transcriptional responses to varied EMF revealed elevation of the anti-oxidative enzymes PRDX6 (2-fold) and DHCR24 (6-fold) in THP1, implying involvement in lipid metabolism. Furthermore, our study confirmed anti-inflammatory effects of EMF by 6-fold increased expression of IL10. Strikingly, THP1 responded to weak EMF, while PBMC were primarily affected by strong EMF, yet with severe cellular stress and enhanced rates of apoptosis, indicated by HSP70 and caspase 3 (CASP3). Taken together, our results emphasize an altered susceptibility of immune cells of different origin and associate EMF-related effects with anti-inflammatory signaling and lipid metabolism.
Vesicular Stomatitis Virus: From Agricultural Pathogen to Vaccine Vector

Vesicular stomatitis virus (VSV), which belongs to the Vesiculovirus genus of the family Rhabdoviridae, is a well studied livestock pathogen and prototypic non-segmented, negative-sense RNA virus. Although VSV is responsible for causing economically significant outbreaks of vesicular stomatitis in cattle, horses, and swine, the virus also represents a valuable research tool for molecular biologists and virologists. Indeed, the establishment of a reverse genetics system for the recovery of infectious VSV from cDNA transformed the utility of this virus and paved the way for its use as a vaccine vector. A highly effective VSV-based vaccine against Ebola virus recently received clinical approval, and many other VSV-based vaccines have been developed, particularly for high-consequence viruses. This review seeks to provide a holistic but concise overview of VSV, covering the virus’s ascension from perennial agricultural scourge to promising medical countermeasure, with a particular focus on vaccines.
Effect of Spirulina Supplementation on Systolic and Diastolic Blood Pressure: Systematic Review and Meta-Analysis of Randomized Controlled Trials

Spirulina is a microalga that presents various important pro-health properties, for instance lowering blood pressure in the research. The study aims to appraise the efficacy of Spirulina administration on systolic (SBP) and diastolic blood pressure (DBP). Randomized controlled trials (RCTs) were retrieved by a systematic search of PubMed, Web of Science, and the Cochrane Library databases from inception to June 2021 according to a standardized protocol. The effect size of each study was counted from mean and standard deviation before and after the intervention and shown as Un-standardized mean difference and 95% confidence interval. Sensitivity analyses were performed. Meta-analysis on 5 RCTs with 230 subjects was eligible. The amount of Spirulina ranged from 1 to 8 g per day, and intervention durations ranged from 2 to 12 weeks. Data analysis indicated that Spirulina supplementation led to a significant lowering of SBP (Mean Difference (MD): −4.59 mmHg, 95% Confidence Interval (CI): −8.20 to −0.99, I square statistic (I2) = 65%) and significant lowering of DBP (MD: −7.02 mmHg, CI: −8.86 to −5.18, I2 = 11%), particularly in a subgroup of hypertensive patients. Spirulina administration might have a supportive effect on the prevention and treatment of hypertension. More exact randomized controlled trials are needed to clarify the effect of Spirulina supplementation on blood pressure.
The Influence of Oxidative Stress on Thyroid Diseases

Thyroid diseases, including neoplasms, autoimmune diseases and thyroid dysfunctions, are becoming a serious social problem with rapidly increasing prevalence. The latter is increasingly linked to oxidative stress. There are many methods for determining the biomarkers of oxidative stress, making it possible to evaluate the oxidative profile in patients with thyroid diseases compared to the healthy population. This opens up a new perspective for investigating the role of elevated parameters of oxidative stress and damage in people with thyroid diseases, especially of neoplastic nature. An imbalance between oxidants and antioxidants is observed at different stages and in different types of thyroid diseases. The organ, which is part of the endocrine system, uses free radicals (reactive oxygen species, ROS) to produce hormones. Thyroid cells release enzymes that catalyse ROS generation; therefore, a key role is played by the internal defence system and non-enzymatic antioxidants that counteract excess ROS not utilised to produce thyroid hormones, acting as a buffer to neutralise free radicals and ensure whole-body homeostasis. An excess of free radicals causes structural cell damage, undermining genomic stability. Looking at the negative effects of ROS accumulation, oxidative stress appears to be implicated in both the initiation and progression of carcinogenesis. The aim of this review is to investigate the oxidation background of thyroid diseases and to summarise the links between redox imbalance and thyroid dysfunction and disease.
Genome-Wide Identification, Characterization and Expression Analysis of the JAZ Gene Family in Resistance to Gray Leaf Spots in Tomato

The plant disease resistance system involves a very complex regulatory network in which jasmonates play a key role in response to external biotic or abiotic stresses. As inhibitors of the jasmonic acid (JA) signaling pathway, JASMONATE ZIM domain (JAZ) proteins have been identified in many plant species, and their functions are gradually being clarified. In this study, 26 JAZ genes were identified in tomato. The physical and chemical properties, predicted subcellular localization, gene structure, cis-acting elements, and interspecies collinearity of 26 SlJAZ genes were subsequently analyzed. RNA-seq data combined with qRT-PCR analysis data showed that the expression of most SlJAZ genes were induced in response to Stemphylium lycopersici, methyl jasmonate (MeJA) and salicylic acid (SA). Tobacco rattle virus RNA2-based VIGS vector (TRV2)-SlJAZ25 plants were more resistant to tomato gray leaf spots than TRV2-00 plants. Therefore, we speculated that SlJAZ25 played a negative regulatory role in tomato resistance to gray leaf spots. Based on combining the results of previous studies and those of our experiments, we speculated that SlJAZ25 might be closely related to JA and SA hormone regulation. SlJAZ25 interacted with SlJAR1, SlCOI1, SlMYC2, and other resistance-related genes to form a regulatory network, and these genes played an important role in the regulation of tomato gray leaf spots. The subcellular localization results showed that the SlJAZ25 gene was located in the nucleus. Overall, this study is the first to identify and analyze JAZ family genes in tomato via bioinformatics approaches, clarifying the regulatory role of SlJAZ25 genes in tomato resistance to gray leaf spots and providing new ideas for improving plant disease resistance.
Usability and Clinical Performance Characteristics of the Asante HIV1/2 Test by Trained Users in Two African Sites

HIV self-testing (HIVST) devices are acknowledged as having the potential to enable the acceleration of HIV diagnosis and linkage to care. How efficiently professional and trained users engaged with the Asante HIV-1/2 Oral Self-Test (Asante) (Sedia Biosciences, Portland, OR, USA), and the accuracy of the device in comparison to other HIV rapid diagnostic tests (RDT), was assessed to be able to guide the development and adoption of the device in Senegal and South Africa. Using convenience sampling, potential participants were recruited from catchment areas where HIV was prevalent. Trained users performed an HIV test on participants using an Oral HIVST. The professional user’s interpretation of results was then measured against the results of various other RDTs. The South African study had 1652 participants and the Senegalese, 500. Most of the participants in each study were 18–35 years old. Senegal had a higher number of females (346/500, 69.2%) compared to South Africa (699/1662, 42.1%). Asante displayed very high sensitivity and specificity when tested against other devices. In the final enzyme-linked immunosorbent assay (ELISA) comparison, in South Africa, the sensitivity: specificity was 99.1:99.9% and in Senegal, 98.4:100.0%. Senegal further identified 53/63 (84.1%) with HIV-1, 8/63 (12.7) with HIV-2 and 2/63 (3.2%) with HIV-1/2 co-infections. Professional or trained users’ interpretations of Asante results correlated strongly to results when using various RDTs, the ELISA assay and Western blot tests, making it a dependable HIV testing instrument.
Transcriptomics-Based Repositioning of Natural Compound, Eudesmin, as a PRC2 Modulator

Extensive epigenetic remodeling occurs during the cell fate determination of stem cells. Previously, we discovered that eudesmin regulates lineage commitment of mesenchymal stem cells through the inhibition of signaling molecules. However, the epigenetic modulations upon eudesmin treatment in genomewide level have not been analyzed. Here, we present a transcriptome profiling data showing the enrichment in PRC2 target genes by eudesmin treatment. Furthermore, gene ontology analysis showed that PRC2 target genes downregulated by eudesmin are closely related to Wnt signaling and pluripotency. We selected DKK1 as an eudesmin-dependent potential top hub gene in the Wnt signaling and pluripotency. Through the ChIP-qPCR and RT-qPCR, we found that eudesmin treatment increased the occupancy of PRC2 components, EZH2 and SUZ12, and H3K27me3 level on the promoter region of DKK1, downregulating its transcription level. According to the analysis of GEO profiles, DEGs by depletion of Oct4 showed an opposite pattern to DEGs by eudesmin treatment. Indeed, the expression of pluripotency markers, Oct4, Sox2, and Nanog, was upregulated upon eudesmin treatment. This finding demonstrates that pharmacological modulation of PRC2 dynamics by eudesmin might control Wnt signaling and maintain pluripotency of stem cells.