Miracle-dz/UniFAR-FTUs huggingface dataset:
Honeycomb-like Structured Film, a Novel Therapeutic Device, Suppresses Tumor Growth in an In Vivo Ovarian Cancer Model

Simple Summary Ovarian cancer cell dissemination can lead to inoperability and death in patients with advanced ovarian cancer. Honeycomb-like structured films (HCFs) are three-dimensional (3D) porous scaffolds fabricated from biodegradable polymers and have been widely used in tissue engineering. We assessed whether HCFs could be a novel strategy to inhibit residual tumor growth after surgery. Here, we show that HCFs can remarkably suppress tumor growth in an in vivo ovarian cancer model. RNA sequencing of paired tumors treated with HCFs and control tumors that were treated without films demonstrated that HCFs induced abnormal focal adhesion and cell morphological change, subsequently inhibiting differentiation, proliferation and motility in ovarian cancer cells. Our data suggest that HCFs could inhibit residual tumor growth after surgery, reduce surgical invasiveness, and improve prognosis for patients with advanced ovarian cancer. Abstract Ovarian cancer cell dissemination can lead to the mortality of patients with advanced ovarian cancer. Complete surgery for no gross residual disease contributes to a more favorable prognosis than that of patients with residual disease. HCFs have highly regular porous structures and their 3D porous structures act as scaffolds for cell adhesion. HCFs are fabricated from biodegradable polymers and have been widely used in tissue engineering. This study aimed to show that HCFs suppress tumor growth in an in vivo ovarian cancer model. The HCF pore sizes had a significant influence on tumor growth inhibition, and HCFs induced morphological changes that rounded out ovarian cancer cells. Furthermore, we identified gene ontology (GO) terms and clusters of genes downregulated by HCFs. qPCR analysis demonstrated that a honeycomb structure downregulated the expression of CXCL2, FOXC1, MMP14, and SNAI2, which are involved in cell proliferation, migration, invasion, angiogenesis, focal adhesion, extracellular matrix (ECM), and epithelial–mesenchymal transition (EMT). Collectively, HCFs induced abnormal focal adhesion and cell morphological changes, subsequently inhibiting the differentiation, proliferation and motility of ovarian cancer cells. Our data suggest that HCFs could be a novel device for inhibiting residual tumor growth after surgery, and could reduce surgical invasiveness and improve the prognosis for patients with advanced ovarian cancer.
Hepatotoxicity of Drugs Used in Multiple Sclerosis, Diagnostic Challenge, and the Role of HLA Genotype Susceptibility

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system and the association with other autoimmune diseases is well-documented. There are many therapeutic options for the treatment of MS. Most of the available drugs cause drug-induced liver injury (DILI) to variable extents with heterogeneous clinical and biological manifestations, including liver injury with or without signs of hypersensitivity and autoimmunity. The diagnosis of DILI may be particularly difficult because MS is frequently associated with idiopathic autoimmune hepatitis. Recent advances suggest that MS and immune-mediated DILI could be promoted by genetic factors, including HLA genotype. In addition, some of these drugs may promote hepatitis B virus reactivation. This review explores the potential hepatotoxicity of drugs used to treat MS and the criteria to distinguish DILI from idiopathic autoimmune hepatitis associated with MS. The role of susceptible genes both promoting MS and causing the hepatotoxicity of the drug used for MS treatment is also discussed.
Transcatheter Arterial Embolization for Alleviating Chronic Musculoskeletal Pain and Improving Physical Function: A Narrative Review

Chronic musculoskeletal pain imposes immense suffering and diminishes the quality of life for millions of patients worldwide; the pain persists despite the use of standard conservative treatments. Increases in our understanding of the pathophysiological mechanisms underlying musculoskeletal disorders indicate the involvement of inappropriate angiogenesis. Accordingly, the resulting neovessels are the target of emerging treatments for chronic musculoskeletal pain, including transarterial embolization. The use of this noninvasive procedure to treat pain refractory to standard therapy in a variety of musculoskeletal conditions is the focus of numerous recent investigations. Here, we describe the pathophysiological indications for the use of transarterial embolization and summarize the findings of studies investigating its use in a variety of histopathological conditions and anatomical sites.
Genomics and Epigenomics in the Molecular Biology of Melanoma—A Prerequisite for Biomarkers Studies

Melanoma is a common and aggressive tumor originating from melanocytes. The increasing incidence of cutaneous melanoma in recent last decades highlights the need for predictive biomarkers studies. Melanoma development is a complex process, involving the interplay of genetic, epigenetic, and environmental factors. Genetic aberrations include BRAF, NRAS, NF1, MAP2K1/MAP2K2, KIT, GNAQ, GNA11, CDKN2A, TERT mutations, and translocations of kinases. Epigenetic alterations involve microRNAs, non-coding RNAs, histones modifications, and abnormal DNA methylations. Genetic aberrations and epigenetic marks are important as biomarkers for the diagnosis, prognosis, and prediction of disease recurrence, and for therapeutic targets. This review summarizes our current knowledge of the genomic and epigenetic changes in melanoma and discusses the latest scientific information.
Perceived smoothness of viewpoint transition in multi-viewpoint stereoscopic displays

Three experiments were conducted to investigate the perceived smoothness of viewpoint transition in multi-view images. Different viewpoints of a stereoscopic scene were generated in real-time. The left-eye and right-eye views of each viewpoint were viewed stereoscopically, from a distance of 120 cm, with shutter glasses synchronized to the display. In Experiment 1, different vantage points of the scene were displayed as the viewer moved his/her head left and right in front of the display. Viewers rated the perceived smoothness of the scene for different viewpoint densities, i.e., number of viewpoints displayed per unit of amplitude of lateral movement, and extent of look-around, i.e., angular separation between the leftmost and rightmost rendered viewpoints. The second and third experiments were similar to the first with the exception that the change in displayed viewpoint was either controlled by the viewer’s hand (Experiment 2) or occurred without any intervention on the part of the viewer (Experiment 3). Perceived smoothness improved with increasing viewpoint density in all three experiments. Perceived smoothness of viewpoint transition was affected by the extent of look-around, but the effect varied across experiments.
Evaluation of the Role of the Activating Application Method in the Cold Sintering Process of ZnO Ceramics Using Ammonium Chloride

The influence of the method of applying the activating additive ammonium chloride and its concentration on the density and microstructure of zinc oxide ceramic obtained by cold sintering at 244 °C was investigated. The activating agent was applied by two methods: impregnation and subsequent autoclave treatment. When the powder was activated by the impregnation method, the crystal sizes remained at the initial level of 0.17–0.19 μm. After the autoclave treatment, the crystal sizes increased to 0.31–0.53 μm. Samples of cold sintering ZnO with relative density up to 0.96 and average grain sizes 0.29–0.86 μm were obtained. ZnO powders and ceramic samples were analyzed using SEM, TGA/DSC, and XRD to reveal the effect of the powder activation method and cold sintering conditions on the material microstructure. The effect of ammonium chloride concentration on grain growth and microstructure of ceramic samples is shown. It was found that the average grain size of ceramic samples with an increase in additive concentration passes through a minimum. In cold sintering of the autoclave activated powder, the effect of reducing the average grain size was observed. The results of this work are discussed on the basis of the idea of the solid-phase mobility of the crystal structure arising when interacting with an aqueous medium.
Juvenile Psoriatic Arthritis: Myth or Reality? An Unending Debate

Juvenile psoriatic arthritis (JPsA) accounts for 1–7% of all cases of juvenile idiopathic arthritis (JIA) and its definition has been a matter of controversy among pediatric rheumatologists for many years. The traditional attribution of JPsA to the spondyloarthropathy group was challenged in the early 1990s, whereas the recent demonstrations of its heterogenous nature have led to questions about its identification as a distinct category in JIA classification. It has been shown that children with the phenotype of JPsA can be divided in two subgroups, one presenting with the features of early-onset ANA-positive JIA, and another that belongs to the spectrum of spondyloarthropathies. The few studies that have compared the clinical characteristics and genetic determinants of JPsA with those of the other JIA categories have obtained contrasting findings. The debate on the categorization of JPsA as a distinct entity within JIA classification is still ongoing and has prompted the revision of its current classification.
Dietary Supplementation with a Blend of Hydrolyzable and Condensed Tannins Ameliorates Diet-Induced Intestinal Inflammation in Zebrafish (Danio rerio)

Simple Summary The huge amount of fish farmed around the world (about 90 million tons in 2020) requires equally large quantities of feed, which is in a great part of animal origin, as it comes from the capture of aquatic species of little commercial value, such as herring, sardines, and krill. Over the years, this crucial natural resource has been decreasing, calling for alternative sources based on plant products that are cheaper and have fewer fluctuations in price and quantity. However, a plant-based diet causes intestinal inflammation, even in fish that are herbivores, such as carp, one of the most cultivated and consumed cyprinids in the world. Zebrafish is a cyprinid that is widely used as a model for biomedical research and more recently for aquaculture. In this study, it was used to develop intestinal inflammation and evaluate the effects of tannins, polyphenols with antioxidant, anti-inflammatory and immunostimulating properties, in counteracting the intestinal proinflammatory effects of a plant-based diet. The results show that tannins can improve the zebrafish intestinal inflammation caused by a terrestrial-plant-based diet. Abstract The current study evaluated the effects of hydrolyzable and condensed tannins from chestnut and quebracho wood, respectively (TSP, Silvafeed®), on zebrafish with intestinal inflammation induced by a plant-based diet (basal diet). Four experimental diets were prepared as follows: the basal diet + 0 TSP, the basal diet + TSP at 0.9 g/kg of feed, the basal diet + TSP at 1.7 g/kg of feed, and the basal diet + TSP at 3.4 g/kg of feed. Eighty-four zebrafish (Danio rerio) were fed for 12 days with the experimental diets. In zebrafish fed the basal diet, intestine integrity appeared to be altered, with damaged intestinal villi, high immunoexpression of tumor necrosis factor-α (TNFα) and cyclooxygenase 2 (COX2), and high expression of the cox2, interleukin 1 (il-1b), interleukin 8 (cxcl8-l1), and tnfα genes. The tannin treatment partially restored intestinal morphology and downregulated the expression of cytokines. The best activity was detected with 1.7 and 3.4 g/kg of feed. In the guts of all groups, Proteobacteria, Fusobacteria, Firmicutes, and Bacteroidetes were the most represented phyla. The most represented genera were Plesiomonas and Sphingomonas, belonging to the Proteobacteria phylum; Cetobacterium, belonging to the Fusobacteria phylum; and Lactobacillus, belonging to the Firmicutes phylum. No significant differences were detected among groups, except for a slight decrease in the Fusobacteria phylum and slight increases in the Shewanella and Bacteroides genera with TSP. In conclusion, these results suggest that tannins can improve the zebrafish intestinal inflammation caused by a terrestrial-plant-based diet in a dose-dependent manner.
Balancing the Risk of Adverse Events against the Efficacy of Immunotherapy in Advanced Thymic Epithelial Tumors

Simple Summary Treatment options for advanced thymic malignancies are limited. Immune checkpoint inhibitors are effective against advanced thymic epithelial tumors, but the treatment is associated with an elevated risk for adverse events. In this article, we aim to highlight new insights regarding predictive markers for treatment efficacy and risk of adverse events that would allow for safe and precise clinical indications for immunotherapy in thymic malignancies. Abstract Thymic epithelial tumors (TETs) are rare thoracic malignancies with a favorable prognosis when complete surgical resection can be achieved. Therapeutic options for advanced, irresectable, or recurrent disease are limited and currently, a therapeutic standard treatment beyond platinum-based chemotherapy is undefined. Immune checkpoint inhibitors are effective against TETs, however their use is associated with a serious risk of immune-mediated toxicity. In this article, we highlight new insights regarding markers of predictive value for both treatment efficacy and risk of adverse effects in immune checkpoint inhibitor treatment for thymic epithelial tumors.
Perception of Parental Attitudes and Self-Efficacy in Refusing Alcohol Drinking and Smoking by Spanish Adolescents: A Cross-Sectional Study

Adolescents are particularly vulnerable to initiation of the use of substances harmful to health, and its increase is cause for concern. The objective of this study was to analyze the relationship between self-efficacy in refusing alcohol and the attitude of adolescents toward drugs and their perception of their parents’ attitude toward refusal. The study was carried out in 2019 in a sample of 1287 students from 11 public high schools in the province of Almería (Spain). Students were aged 14 to 18 in their 3rd and 4th year of compulsory secondary education. The Drinking Refusal Self-Efficacy Questionnaire—Revised Adolescent version (DRSEQ-RA), Attitudes Toward Taking Drugs—Basic BIP Scale and the Parents’ attitudes Toward Drug Use were administered. The results showed that family relationships seem to have a direct impact on adolescent patterns in smoking and drinking alcohol. However, a favorable attitude toward drugs is a risk factor for drinking alcohol and smoking tobacco. The self-efficacy dimension also acts as a protective factor against the probability of using alcohol or tobacco. The conclusions emphasized that communication within the family core can increase or decrease the risk of adolescents using substances harmful to health.
Multiple Roles of PLK1 in Mitosis and Meiosis

Cells are equipped with a diverse network of signaling and regulatory proteins that function as cell cycle regulators and checkpoint proteins to ensure the proper progression of cell division. A key regulator of cell division is polo-like kinase 1 (PLK1), a member of the serine/threonine kinase family that plays an important role in regulating the mitotic and meiotic cell cycle. The phosphorylation of specific substrates mediated by PLK1 controls nuclear envelope breakdown (NEBD), centrosome maturation, proper spindle assembly, chromosome segregation, and cytokinesis. In mammalian oogenesis, PLK1 is essential for resuming meiosis before ovulation and for establishing the meiotic spindle. Among other potential roles, PLK1 regulates the localized translation of spindle-enriched mRNAs by phosphorylating and thereby inhibiting the translational repressor 4E-BP1, a downstream target of the mTOR (mammalian target of rapamycin) pathway. In this review, we summarize the functions of PLK1 in mitosis, meiosis, and cytokinesis and focus on the role of PLK1 in regulating mRNA translation. However, knowledge of the role of PLK1 in the regulation of meiosis remains limited.
Interventional Occlusion of Large Patent Ductus Arteriosus in Adults with Severe Pulmonary Hypertension

(1) Background: the indications for transcatheter closure of large patent ductus arteriosus (PDA) with severe pulmonary hypertension (PH) are still unclear, and scholars have not fully elucidated the factors that affect PH prognosis. (2) Methods: we retrospectively enrolled 134 consecutive patients with a PDA diameter ≥10 mm or a ratio of PDA and aortic >0.5. We collected clinical data to explore the factors affecting follow-up PH. (3) Results: 134 patients (mean age 35.04 ± 10.23 years; 98 women) successfully underwent a transcatheter closure, and all patients had a mean pulmonary artery pressure (mPAP) >50 mmHg. Five procedures were deemed to have failed because their mPAP did not decrease, and the patients experienced uncomfortable symptoms after the trial occlusion. The average occluder (pulmonary end) size was almost twice the PDA diameter (22.33 ± 4.81 mm vs. 11.69 ± 2.18 mm). Left ventricular end-diastolic dimension (LVEDD), mPAP, and left ventricular ejection fraction (LVEF) significantly reduced after the occlusion, and LVEF recovered during the follow-up period. In total, 42 of the 78 patients with total pulmonary resistance >4 Wood Units experienced clinical outcomes, and all of them had PH in the follow-up, while 10 of them had heart failure, and 4 were hospitalized again because of PH. The results of a logistic regression analysis revealed that the postoperative mPAP had an independent risk factor (odds ratio = 1.069, 95% confidence interval: 1.003 to 1.140, p = 0.040) with a receiver operating characteristic curve cut-off value of 35.5 mmHg (p < 0.001). (4) Conclusions: performing a transcatheter closure of large patent ductus arteriosus is feasible, and postoperative mPAP was a risk factor that affected the follow-up PH. Patients with a postoperative mPAP >35.5 mmHg should be considered for targeted medical therapy or should undergo right heart catheterization again after the occlusion.
Drug Repurposing against KRAS Mutant G12C: A Machine Learning, Molecular Docking, and Molecular Dynamics Study

The Kirsten rat sarcoma viral G12C (KRASG12C) protein is one of the most common mutations in non-small-cell lung cancer (NSCLC). KRASG12C inhibitors are promising for NSCLC treatment, but their weaker activity in resistant tumors is their drawback. This study aims to identify new KRASG12C inhibitors from among the FDA-approved covalent drugs by taking advantage of artificial intelligence. The machine learning models were constructed using an extreme gradient boosting (XGBoost) algorithm. The models can predict KRASG12C inhibitors well, with an accuracy score of validation = 0.85 and Q2Ext = 0.76. From 67 FDA-covalent drugs, afatinib, dacomitinib, acalabrutinib, neratinib, zanubrutinib, dutasteride, and finasteride were predicted to be active inhibitors. Afatinib obtained the highest predictive log-inhibitory concentration at 50% (pIC50) value against KRASG12C protein close to the KRASG12C inhibitors. Only afatinib, neratinib, and zanubrutinib covalently bond at the active site like the KRASG12C inhibitors in the KRASG12C protein (PDB ID: 6OIM). Moreover, afatinib, neratinib, and zanubrutinib exhibited a distance deviation between the KRASG2C protein-ligand complex similar to the KRASG12C inhibitors. Therefore, afatinib, neratinib, and zanubrutinib could be used as drug candidates against the KRASG12C protein. This finding unfolds the benefit of artificial intelligence in drug repurposing against KRASG12C protein.
From text to interaction: The digital advance directive method for advance directives

Advance directives allow people to specify individual treatment preferences in case of decision-making incapacity involving decisions of utmost importance. There are many tools that provide information on the topic, digital forms for structured data input, or platforms that support data storage and availability. Yet, there is no tool supporting the innermost process of an advance directive: decision making itself. To address this issue, we developed a visual-interactive, semi-quantitative method for generating digital advance directives (DiADs) that harnesses the potential of digitalization in healthcare. In this article, we describe the DiAD method and its app lined with the exemplary narrative of user Mr S. linking the theory to an exemplary use case. The DiAD method is intended to lower barriers and increase comfort in creating an advance directive by shifting the focus from heavily text-based processes to visual representation and interaction, that is, from text to reflection.
Effects of Chokeberries (Aronia spp.) on Cytoprotective and Cardiometabolic Markers and Semen Quality in 109 Mildly Hypercholesterolemic Danish Men: A Prospective, Double-Blinded, Randomized, Crossover Trial

Background: Chokeberries (Aronia spp.) are known to exhibit both direct and indirect antioxidant properties and have been associated with beneficial effects on human health, including cardiovascular risk factors (inflammation, serum lipids, sugars, blood pressure), oxidative stress, and semen quality. This prospective, double-blinded, randomized, crossover clinical trial was conducted to elucidate the effects of Aronia supplementation on these health targets in mildly hypercholesterolemic men. Methods: The standardized Aronia supplementation comprised three wild Aronia spp. (A. arbutifolia, A prunifolia and A. melanocarpa) and the Aronia hybrid × Sorbaronia mitschurinii (standardized to 150 mg anthocyanins daily). Participants (n = 109) were healthy men with respect to all outcome targets except for the total cholesterol level (5.0–7.0 mM). Participants were randomized to supplementation with either Aronia or placebo for 90 days, followed by a wash-out period and lastly the complementary supplementation. Effects on the health parameters were compared among both the whole group of men and in subgroups according to age, body mass index (BMI), lifestyle, dietary habits, and serum glutathione levels at baseline. The study is registered in ClinicalTrials.gov. : NCT03405753. Results: Glutathione levels were significantly improved after 90 days intake of Aronia supplementation compared to placebo in the subgroup of men with a low level of glutathione at baseline (p = 0.038) and a high coffee intake (p = 0.045). A significant decrease in levels of sperm DNA fragmentation and an increase in the percentage of motile sperm were observed in men aged >40 and in men with BMI > 25. Further, these parameters were significantly improved in the dietary subgroup defined by a high level of coffee intake. Total cholesterol and low-density lipoprotein-cholesterol levels decreased significantly in men <40 years after Aronia supplementation. No statistically significant effects were observed regarding blood pressure, markers of blood sugar regulation, hemoglobin A1c, superoxide dismutase, catalase, isoprostane levels, high sensitivity C reactive protein, or other semen parameters. Conclusions: This study demonstrated a significant increase in glutathione levels and improvement of cytoprotective targets following Aronia supplementation in specific subgroups of men >40 years of age and BMI > 25 but did not demonstrate a significant effect in the overall analysis. The observed concurrent increase in glutathione levels and improvement of cytoprotective targets following Aronia supplementation in subgroups of men, suggests that the endogenous phase II antioxidant glutathione is involved in the modulation of the observed cytoprotective effects. This study is a good foundation for further investigation of these cytoprotective effects in groups with oxidative stress in a dose–response study.