Miracle-dz/UniFAR-FTUs huggingface dataset:
MIR29A Impedes Metastatic Behaviors in Hepatocellular Carcinoma via Targeting LOX, LOXL2, and VEGFA

Primary liver cancer accounts for the third most deadly type of malignant tumor globally, and approximately 80% of the cases are hepatocellular carcinoma (HCC), which highly relies on the activity of hypoxia responsive pathways to bolster its metastatic behaviors. MicroRNA-29a (MIR29A) has been shown to exert a hepatoprotective effect on hepatocellular damage and liver fibrosis induced by cholestasis and diet stress, while its clinical and biological role on the activity hypoxia responsive genes including LOX, LOXL2, and VEGFA remains unclear. TCGA datasets were retrieved to confirm the differential expression and prognostic significance of all genes in the HCC and normal tissue. The Gene Expression Omnibus (GEO) dataset was used to corroborate the differential expression and diagnostic value of MIR29A. The bioinformatic identification were conducted to examine the interaction of MIR29A with LOX, LOXL2, and VEGFA. The suppressive activity of MIR29A on LOX, LOXL2, and VEGF was verified by qPCR, immunoblotting, and luciferase. The effect of overexpression of MIR29A-3p mimics in vitro on apoptosis markers (caspase-9, -3, and poly (ADP-ribose) polymerase (PARP)); cell viability and wound healing performance were examined using immunoblot and a WST-1 assay and a wound healing assay, respectively. The HCC tissue presented low expression of MIR29A, yet high expression of LOX, LOXL2, and VEGFA as compared to normal control. Serum MIR29A of HCC patients showed decreased levels as compared to that of normal control, with an area under curve (AUC) of 0.751 of a receiver operating characteristic (ROC) curve. Low expression of MIR29A and high expression of LOX, LOXL2, and VEGFA indicated poor overall survival (OS). MIR29A-3p was shown to target the 3′UTR of LOX, LOXL2, and VEGFA. Overexpression of MIR29A-3p mimic in HepG2 cells led to downregulated gene and protein expression levels of LOX, LOXL2, and VEGFA, wherein luciferase reporter assay confirmed that MIR29A-3p exerts the inhibitory activity via directly binding to the 3′UTR of LOX and VEGFA. Furthermore, overexpression of MIR29A-3p mimic induced the activity of caspase-9 and -3 and PARP, while it inhibited the cell viability and wound healing performance. Collectively, this study provides novel insight into a clinical-applicable panel consisting of MIR29, LOX, LOXL2, and VEGFA and demonstrates an anti-HCC effect of MIR29A via comprehensively suppressing the expression of LOX, LOXL2, and VEGFA, paving the way to a prospective theragnostic approach for HCC.
All-Cause Mortality Risk in National Prostate Cancer Cohort: An Impact of Population-Based Prostate Cancer Screening

The aim of this study is to evaluate all-cause mortality risk differences before and during prostate cancer screening, with a profound focus on the differences between screened and not-screened patient groups. Prostate cancer cases diagnosed between 1998 and 2016 were identified from the population-based Lithuanian Cancer Registry and linked with screening status in the National Health Insurance Fund database. The analysis was stratified by a period of diagnosis and screening status. Standardized mortality ratios (SMRs) were used to assess all-cause and cause-specific mortality risk. The SMRs were calculated by dividing the observed number of deaths among prostate cancer patients by the expected number of deaths from the general population. All-cause SMR (1.45 (95% CI 1.42–1.48)) in the pre-screening period was higher compared to the screening period (SMR = 1.17 (95% CI 1.15–1.19)). An increased all-cause mortality risk among prostate cancer patients was observed in the not-screened patient population (SMR = 1.76 (95% CI 1.71–1.82)), while all-cause mortality risk in the screened patient population was similar to the general population (SMR = 1.00 (95% CI 0.97–1.02)). Screened patients with localized stage of disease had lower all-cause mortality risk than the general population (SMR = 0.72 (95% CI 0.70–0.75)). In conclusion, men with prostate cancer in Lithuania had excess all-cause mortality risk compared to the general population. The all-cause mortality risk among screened patients was not higher than expected.
Characteristics and Clinical Value of 18F-FDG PET/CT in the Management of Adult-Onset Still’s Disease: 35 Cases

While the diagnosis of adult-onset Still’s disease (AOSD) involves the exclusion of differential diagnoses, the characteristics and value of 18F-Fluorodeoxyglucose (18F-FDG) Positron Emission Tomography coupled with CT (PET/CT) in the management of AOSD remain poorly known. Our retrospective study included patients from four centers, fulfilling Yamaguchi or Fautrel criteria, who underwent a PET/CT during an active AOSD. Thirty-five patients were included. At the time of PET/CT, the Yamaguchi criteria were met in 23 of 29 evaluable cases. PET/CT showed bone marrow (74.3%), lymph node (74.3%), and splenic (48.6%) FDG uptake. Despite arthralgia or arthritis in most patients, joints were rarely the sites of 18F-FDG accumulation. The spatial distribution of 18F-FDG uptake was nonspecific, and its intensity could be similar to malignant disease. Lymph node or bone marrow biopsy was performed after PET/CT in 20 patients (57.1%). The intensity of bone marrow; splenic and lymph node hypermetabolism appeared to be correlated with disease activity. Abnormal PET/CT in the cervical lymph nodes and age ≥ 60 years seemed to be predictive factors for monocyclic evolution. The clinical value of PET/CT is not in direct diagnosis; but as an aid in excluding differential diagnoses by searching for their scintigraphic features and guiding biopsy.
Flexible antibacterial Zr-Cu-N thin films resistant to cracking

This study investigates how the Cu concentration in Zr-Cu-N films affects the films' antibacterial capacity and mechanical properties. Zr-Cu-N films were prepared by reactive magnetron sputtering from composed Zr/Cu targets using a dual magnetron in an Ar + N2 mixture. The antibacterial capacity of Zr-Cu-N films was tested on Escherichia coli (E. coli) bacteria. The mechanical properties of Zr-Cu-N films were determined from the load vs. displacement curves measured using a Fisherscope H 100 microhardness tester. The antibacterial capacity was modulated by the amount of Cu added to the Zr-Cu-N film. The mechanical properties were varied based on the energy Ei delivered to the growing film by bombarding ions. It was found that it is possible to form Zr-Cu-N films with Cu concentrations ≥10 at. % that simultaneously exhibit (1) 100% killing efficiency Ek for E. coli bacteria on their surfaces, and (2) (1) high hardness H of about 25 GPa, (2) high ratio H/E* ≥ 0.1, (3) high elastic recovery We ≥ 60% and (4) .
Large Stabilization Effects by Intramolecular Beryllium Bonds in Ortho-Benzene Derivatives

Intramolecular interactions are shown to be key for favoring a given structure in systems with a variety of conformers. In ortho-substituted benzene derivatives including a beryllium moiety, beryllium bonds provide very large stabilizations with respect to non-bound conformers and enthalpy differences above one hundred kJ·mol−1 are found in the most favorable cases, especially if the newly formed rings are five or six-membered heterocycles. These values are in general significantly larger than hydrogen bonds in 1,2-dihidroxybenzene. Conformers stabilized by a beryllium bond exhibit the typical features of this non-covalent interaction, such as the presence of a bond critical point according to the topology of the electron density, positive Laplacian values, significant geometrical distortions and strong interaction energies between the donor and acceptor quantified by using the Natural Bond Orbital approach. An isodesmic reaction scheme is used as a tool to measure the strength of the beryllium bond in these systems in terms of isodesmic energies (analogous to binding energies), interaction energies and deformation energies. This approach shows that a huge amount of energy is spent on deforming the donor–acceptor pairs to form the new rings.
Associations between Natural Resource Extraction and Incidence of Acute and Chronic Health Conditions: Evidence from Tanzania

Natural resource extraction projects are often accompanied by complex environmental and social-ecological changes. In this paper, we evaluated the association between commodity extraction and the incidence of diseases. We retrieved council (district)-level outpatient data from all public and private health facilities from the District Health Information System (DHIS2). We combined this information with population data from the 2012 national population census and a geocoded list of resource extraction projects from the Geological Survey of Tanzania (GST). We used Poisson regression with random effects and cluster-robust standard errors to estimate the district-level associations between the presence of three types of commodity extraction (metals, gemstone, and construction materials) and the total number of patients in each disease category in each year. Metal extraction was associated with reduced incidence of several diseases, including chronic diseases (IRR = 0.61, CI: 0.47–0.80), mental health disorders (IRR = 0.66, CI: 0.47–0.92), and undernutrition (IRR = 0.69, CI: 0.55–0.88). Extraction of construction materials was associated with an increased incidence of chronic diseases (IRR = 1.47, CI: 1.15–1.87). This study found that the presence of natural resources commodity extraction is significantly associated with changes in disease-specific patient volumes reported in Tanzania’s DHIS2. These associations differed substantially between commodities, with the most protective effects shown from metal extraction.
Exercise Inhibits Doxorubicin-Induced Damage to Cardiac Vessels and Activation of Hippo/YAP-Mediated Apoptosis

Simple Summary We developed a juvenile mouse cardiotoxicity model and demonstrated that doxorubicin treatment led to cardiac vascular damage involving a decrease in vascular endothelial cells and pericytes. By contrast, cardiac vessels in mice treated with exercise (Ex) during Dox treatment had no change in vascular endothelial cells or pericyte coverage. Here we show that exercise during Dox induced the migration of bone marrow (BM) stem cells into the heart with their differentiation into vascular endothelial cells and pericytes. These data define a new mechanism of Dox-induced cardiotoxicity and suggest that Ex inhibits vascular damage by promoting bone marrow (BM) stem cell-mediated cardiac vessel repair. We also show that Ex inhibits Hippo-YAP signaling-mediated apoptosis in cardiomyocytes. Ex may be an effective intervention strategy. Targeting Hippo-YAP signaling may also offer another novel therapeutic option to protect the heart. Abstract Dose-related cardiomyopathy is a major side effect following doxorubicin (Dox). To investigate whether exercise (Ex)-induced vasculogenesis plays a role in reducing Dox-induced cardiotoxicity, GFP+ bone marrow (BM) cells from GFP transgenic mice were transplanted into wild-type mice. Transplanted mice were treated with Dox, Ex, Dox+Ex, or control. We found Dox therapy resulted in decreased systolic and diastolic blood flow, decreased ejection fraction and fractional shortening, and decreased vascular endothelial cells and pericytes. These abnormalities were not seen in Dox+Ex hearts. Heart tissues from control-, Ex-, or Dox-treated mice showed a small number of GFP+ cells. By contrast, the Dox+Ex-treated hearts had a significant increase in GFP+ cells. Further analyses demonstrated these GFP+ BM cells had differentiated into vascular endothelial cells (GFP+CD31+) and pericytes (GFP+NG2+). Decreased cardiomyocytes were also seen in Dox-treated but not Dox+Ex-treated hearts. Ex induced an increase in GFP+c-Kit+ cells. However, these c-Kit+ BM stem cells had not differentiated into cardiomyocytes. Dox therapy induced phosphorylation of MST1/2, LATS1, and YAP; a decrease in total YAP; and cleavage of caspase-3 and PARP in the heart tissues. Dox+Ex prevented these effects. Our data demonstrated Dox-induced cardiotoxicity is mediated by vascular damage resulting in decreased cardiac blood flow and through activation of Hippo-YAP signaling resulting in cardiomyocyte apoptosis. Furthermore, Ex inhibited these effects by promoting migration of BM stem cells into the heart to repair the cardiac vessels damaged by Dox and through inhibiting Dox-induced Hippo-YAP signaling-mediated apoptosis. These data support the concept of using exercise as an intervention to decrease Dox-induced cardiotoxicity.
A Meta-Analysis of the Influence of Antipsychotics on Cytokines Levels in First Episode Psychosis

Background: Cytokines have a major impact on the neurotransmitter networks that are involved in schizophrenia pathophysiology. First Episode Psychosis (FEP) patients exhibit abnormalities in cytokines levels prior to the start of treatment. Previous studies showed that antipsychotic treatment modulates cytokines levels. The aim of this meta-analysis is to further investigate this relationship. Methods: Several online databases were searched. For meta-analysis of selected studies, we analysed variables containing the number of cases, mean and standard deviation of IL-1β, IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α, IFN-γ levels before, and after, antipsychotic treatment. Results: 12 studies were included in the meta-analysis. Our main results demonstrate that, in FEP patients, antipsychotic treatment is related to decreased concentrations of pro-inflammatory IL-1β, IL-6, IFN-γ, TNF-α and anti-inflammatory IL-4, IL-10 cytokines. On the other hand, levels of pro-inflammatory IL-2 and IL-17 remain unaffected. Conclusions: When compared with other meta-analyses of studies involving FEP individuals, results we obtained are consistent regarding decrease in IL-1β, IL-6. Comparing outcomes of our study with meta-analyses of schizophrenic subjects, in general, our results are consistent in IL-1β, IL-6, TNF-α, IFN-γ, IL-2. Our meta-analysis is the only one which indicates a decrease in anti-inflammatory IL-10 in FEP patients after antipsychotic treatment.
Prognostic and Therapeutic Role of Angiogenic Microenvironment in Thyroid Cancer

Simple Summary Angiogenesis is an essential event for the progression of solid tumors and is promoted by angiogenic cytokines released in the tumor microenvironment by neoplastic and stromal cells. Over the last 20 years, the role of the microenvironment and the implication of several angiogenic factors in tumorigenesis of solid and hematological neoplasms have been widely studied. The tumor microenvironment has also been well-defined for thyroid cancer, clarifying the importance of angiogenesis in cancer progression, spread, and metastasis. Furthermore, recent studies have evaluated the association of circulating angiogenic factors with the clinical outcomes of differentiated thyroid cancer, potentially providing noninvasive, low-cost, and safe tests that can be used in screening, diagnosis, and follow-up. In this review, we highlight the mechanisms of action of these proangiogenic factors and their different molecular pathways, as well as their applications in the treatment and prognosis of thyroid cancer. Abstract Thyroid cancer is the most common endocrine malignancy, with a typically favorable prognosis following standard treatments, such as surgical resection and radioiodine therapy. A subset of thyroid cancers progress to refractory/metastatic disease. Understanding how the tumor microenvironment is transformed into an angiogenic microenvironment has a role of primary importance in the aggressive behavior of these neoplasms. During tumor growth and progression, angiogenesis represents a deregulated biological process, and the angiogenic switch, characterized by the formation of new vessels, induces tumor cell proliferation, local invasion, and hematogenous metastases. This evidence has propelled the scientific community’s effort to study a number of molecular pathways (proliferation, cell cycle control, and angiogenic processes), identifying mediators that may represent viable targets for new anticancer treatments. Herein, we sought to review angiogenesis in thyroid cancer and the potential role of proangiogenic cytokines for risk stratification of patients. We also present the current status of treatment of advanced differentiated, medullary, and poorly differentiated thyroid cancers with multiple tyrosine kinase inhibitors, based on the rationale of angiogenesis as a potential therapeutic target.
Radar Sensing for Activity Classification in Elderly People Exploiting Micro-Doppler Signatures Using Machine Learning

The health status of an elderly person can be identified by examining the additive effects of aging along with disease linked to it and can lead to ‘unstable incapacity’. This health status is determined by the apparent decline of independence in activities of daily living (ADLs). Detecting ADLs provides possibilities of improving the home life of elderly people as it can be applied to fall detection systems. This paper presents fall detection in elderly people based on radar image classification by examining their daily routine activities, using radar data that were previously collected for 99 volunteers. Machine learning techniques are used classify six human activities, namely walking, sitting, standing, picking up objects, drinking water and fall events. Different machine learning algorithms, such as random forest, K-nearest neighbours, support vector machine, long short-term memory, bi-directional long short-term memory and convolutional neural networks, were used for data classification. To obtain optimum results, we applied data processing techniques, such as principal component analysis and data augmentation, to the available radar images. The aim of this paper is to improve upon the results achieved using a publicly available dataset to further improve upon research of fall detection systems. It was found out that the best results were obtained using the CNN algorithm with principal component analysis and data augmentation together to obtain a result of 95.30% accuracy. The results also demonstrated that principal component analysis was most beneficial when the training data were expanded by augmentation of the available data. The results of our proposed approach, in comparison to the state of the art, have shown the highest accuracy.
Venom-Derived Neurotoxins Targeting Nicotinic Acetylcholine Receptors

Acetylcholine was the first neurotransmitter described. The receptors targeted by acetylcholine are found within organisms spanning different phyla and position themselves as very attractive targets for predation, as well as for defense. Venoms of snakes within the Elapidae family, as well as those of marine snails within the Conus genus, are particularly rich in proteins and peptides that target nicotinic acetylcholine receptors (nAChRs). Such compounds are invaluable tools for research seeking to understand the structure and function of the cholinergic system. Proteins and peptides of venomous origin targeting nAChR demonstrate high affinity and good selectivity. This review aims at providing an overview of the toxins targeting nAChRs found within venoms of different animals, as well as their activities and the structural determinants important for receptor binding.
Environment Actors Confronting a Post Climate-Related Disaster Scenario: A Feasibility Study of an Action-Based Intervention Aiming to Promote Climate Action

(1) A climate change awareness-action gap still prevails in our society, with individuals showing significant social inertia regarding environmental issues. The communication on climate change is pointed out as one of the causes of the social inertia; (2) Following an action-oriented transformation research, the main goal of this study was to ascertain the feasibility of an action-based communication intervention, based on the participants’ exposure to a post climate-related disaster scenario. The feasibility of the action-based communication intervention was assessed in a focus group meeting, whose content was qualitatively analysed; (3) The results of this study demonstrate that action-based communication interventions are feasible to trigger an attitude transformation, catalysed by the experiential processing of climate change and by the affect arousal; (4) This study comes to contribute to a transformation of the climate change communication praxis, by highlighting the urgency to shift the for a new paradigm of communicating climate change, in which the affect and the experiential processing should account for conveying environment-related information in order to promote society’s climate action.
Off-Target-Based Design of Selective HIV-1 PROTEASE Inhibitors

The approval of the first HIV-1 protease inhibitors (HIV-1 PRIs) marked a fundamental step in the control of AIDS, and this class of agents still represents the mainstay therapy for this illness. Despite the undisputed benefits, the necessary lifelong treatment led to numerous severe side-effects (metabolic syndrome, hepatotoxicity, diabetes, etc.). The HIV-1 PRIs are capable of interacting with “secondary” targets (off-targets) characterized by different biological activities from that of HIV-1 protease. In this scenario, the in-silico techniques undoubtedly contributed to the design of new small molecules with well-fitting selectivity against the main target, analyzing possible undesirable interactions that are already in the early stages of the research process. The present work is focused on a new mixed-hierarchical, ligand-structure-based protocol, which is centered on an on/off-target approach, to identify the new selective inhibitors of HIV-1 PR. The use of the well-established, ligand-based tools available in the DRUDIT web platform, in combination with a conventional, structure-based molecular docking process, permitted to fast screen a large database of active molecules and to select a set of structure with optimal on/off-target profiles. Therefore, the method exposed herein, could represent a reliable help in the research of new selective targeted small molecules, permitting to design new agents without undesirable interactions.
Effects of Padel Competition on Brain Health-Related Myokines

Padel is becoming one of the most widespread racket sports that may have potential health benefits. Considering that several myokines mediate the cross-talk between skeletal muscles and the brain, exerting positive effects on brain health status, this study was designed to evaluate the responses of brain-derived neurotrophic factor (BDNF), leukemia inhibitory factor (LIF), and irisin (IR) to padel competition in trained players and to determine whether these responses were sex-dependent. Twenty-four trained padel players (14 women and 10 men with a mean age of 27.8 ± 6.3 years) participated voluntarily in this study. Circulating levels of BDNF, LIF, and IR were assessed before and after simulated padel competition (real playing time, 27.8 ± 8.49 min; relative intensity, 75.2 ± 7.9% maximum heart rate). Except for BDNF responses observed in female players (increasing from 1531.12 ± 269.09 to 1768.56 ± 410.75 ng/mL), no significant changes in LIF and IR concentrations were reported after padel competition. In addition, no sex-related differences were found. Moreover, significant associations between IR and BDNF were established at both pre- and post-competition. Our results suggest that while competitive padel practice stimulates BDNF response in female players, padel competition failed to boost the release of LIF and IR. Future studies are needed to further explore the role of these exercise-induced myokines in the regulation of brain functions and to identify the field sports that can contribute to myokine-mediated muscle–brain crosstalk.