Miracle-dz/UniFAR-FTUs huggingface dataset:
Potential Therapies Targeting the Metabolic Reprogramming of Diabetes-Associated Breast Cancer

In recent years, diabetes-associated breast cancer has become a significant clinical challenge. Diabetes is not only a risk factor for breast cancer but also worsens its prognosis. Patients with diabetes usually show hyperglycemia and hyperinsulinemia, which are accompanied by different glucose, protein, and lipid metabolism disorders. Metabolic abnormalities observed in diabetes can induce the occurrence and development of breast cancer. The changes in substrate availability and hormone environment not only create a favorable metabolic environment for tumorigenesis but also induce metabolic reprogramming events required for breast cancer cell transformation. Metabolic reprogramming is the basis for the development, swift proliferation, and survival of cancer cells. Metabolism must also be reprogrammed to support the energy requirements of the biosynthetic processes in cancer cells. In addition, metabolic reprogramming is essential to enable cancer cells to overcome apoptosis signals and promote invasion and metastasis. This review aims to describe the major metabolic changes in diabetes and outline how cancer cells can use cellular metabolic changes to drive abnormal growth and proliferation. We will specifically examine the mechanism of metabolic reprogramming by which diabetes may promote the development of breast cancer, focusing on the role of glucose metabolism, amino acid metabolism, and lipid metabolism in this process and potential therapeutic targets. Although diabetes-associated breast cancer has always been a common health problem, research focused on finding treatments suitable for the specific needs of patients with concurrent conditions is still limited. Most studies are still currently in the pre-clinical stage and mainly focus on reprogramming the glucose metabolism. More research targeting the amino acid and lipid metabolism is needed.
Thermo-Mechanical Fatigue Behavior and Resultant Microstructure Evolution in Al-Si 319 and 356 Cast Alloys

The out-of-phase thermo-mechanical fatigue (TMF) behavior of the two Al-Si cast alloys most widely used for engine applications (319 and 356) were investigated under temperature cycling (60–300 °C) and various strain amplitudes (0.1–0.6%). The relationship between the microstructural evolution and TMF behavior was closely studied. Both alloys exhibited asymmetric hysteresis loops with a higher portion in the tensile mode during TMF cycling. The two alloys showed cyclic softening behavior with regard to the maximum stress, but an earlier inflection of cyclic stress was found in the 356 alloy. The TMF lifetime of the 319 alloy was generally longer than that of the 356 alloy, especially at higher strain amplitudes. All the precipitates (β′-MgSi in 356 and θ′-Al2Cu in 319) coarsened during the TMF tests; however, the coarsening rate per cycle in the 356 alloy was significantly higher than that in the 319 alloy. An energy-based model was applied to predict the fatigue lifetime, which corresponded well with the experimental data. However, the parameters in the model varied with the alloys, and the 356 alloy exhibited a lower fatigue damage capacity and a higher fatigue damage exponent.
Hope-Based Program for Portuguese Outpatients with Advanced Chronic Illness in a Community Setting: A Randomized Control Trial

Background: Hope is widely considered a subjective phenomenon able to bring beneficial consequences to human health and existence. Maintaining hope amid a life-threatening disease and during palliative care is critical. The study aims to examine the effectiveness of a psychosocial supportive Hope Promotion Program (HPP) in enhancing hope, comfort, and quality of life in Portuguese adult outpatients with advanced and progressive chronic illness. Method: Using a parallel Randomized Control Trial (RCT) with pre-post design, 56 cancer outpatients from two day hospitals. Participants were randomly assigned to either a control group (n = 28) or an intervention group (n = 28). The primary outcome measure was hope. Secondary measures included comfort and quality of life. Participants were assessed at baseline, day 15, and day 30 of follow-up. Results: Baseline characteristics were similar between the two groups. In the intervention group, there was a significant increase in the total hope scores after the HPP (day 15). Significant differences were still present after one month (p < 0.05). There was also a significant increase in comfort and quality of life scores in the intervention group one month after HPP (p = 0.018). Conclusions: The HPP may be an effective intervention to increase hope and improve comfort and quality of life among palliative patients. Future studies should increase sample size, diversify settings, and include longer and more detailed follow-ups.
Lp Centroidal Voronoi Tessellation and its applications

This paper introduces Lp-Centroidal Voronoi Tessellation (Lp-CVT), a generalization of CVT that minimizes a higher-order moment of the coordinates on the Voronoi cells. This generalization allows for aligning the axes of the Voronoi cells with a predefined background tensor field (anisotropy). Lp-CVT is computed by a quasi-Newton optimization framework, based on closed-form derivations of the objective function and its gradient. The derivations are given for both surface meshing (Ω is a triangulated mesh with per-facet anisotropy) and volume meshing (Ω is the interior of a closed triangulated mesh with a 3D anisotropy field). Applications to anisotropic, quad-dominant surface remeshing and to hexdominant volume meshing are presented. Unlike previous work, Lp-CVT captures sharp features and intersections without requiring any pre-tagging.
Evaluation of Antioxidant and Anticancer Activity of Mono- and Polyfloral Moroccan Bee Pollen by Characterizing Phenolic and Volatile Compounds

Bee pollen is frequently characterized as a natural source of bioactive components, such as phenolic compounds, which are responsible for its pharmaceutical potential and nutritional properties. In this study, we evaluated the bioactive compound contents of mono- and polyfloral bee pollen samples using spectroscopic and chromatographic methods and established links with their antioxidant and antitumor activity. The findings demonstrated that the botanical origin of bee pollen has a remarkable impact on its phenolic (3–17 mg GAE/g) and flavonoid (0.5–3.2 mg QE/g) contents. Liquid chromatography–mass spectrometry analysis revealed the presence of 35 phenolic and 13 phenylamide compounds in bee pollen, while gas chromatography–mass spectrometry showed its richness in volatiles, such as hydrocarbons, fatty acids, alcohols, ketones, etc. The concentration of bioactive compounds in each sample resulted in a substantial distinction in their antioxidant activity, DPPH (EC50: 0.3–0.7 mg/mL), ABTS (0.8–1.3 mM Trolox/mg), and reducing power (0.03–0.05 mg GAE/g), with the most bioactive pollens being the monofloral samples from Olea europaea and Ononis spinosa. Complementarily, some samples revealed a moderate effect on cervical carcinoma (GI50: 495 μg/mL) and breast adenocarcinoma (GI50: 734 μg/mL) cell lines. This may be associated with compounds such as quercetin-O-diglucoside and kaempferol-3-O-rhamnoside, which are present in pollens from Olea europaea and Coriandrum, respectively. Overall, the results highlighted the potentiality of bee pollen to serve health-promoting formulations in the future.
Monodisperse Micro-Droplet Generation in Microfluidic Channel with Asymmetric Cross-Sectional Shape

Micro-droplets are widely used in the fields of chemical and biological research, such as drug delivery, material synthesis, point-of-care diagnostics, and digital PCR. Droplet-based microfluidics has many advantages, such as small reagent consumption, fast reaction time, and independent control of each droplet. Therefore, various micro-droplet generation methods have been proposed, including T-junction breakup, capillary flow-focusing, planar flow-focusing, step emulsification, and high aspect (height-to-width) ratio confinement. In this study, we propose a microfluidic device for generating monodisperse micro-droplets, the microfluidic channel of which has an asymmetric cross-sectional shape and high hypotenuse-to-width ratio (HTWR). It was fabricated using basic MEMS processes, such as photolithography, anisotropic wet etching of Si, and polydimethylsiloxane (PDMS) molding. Due to the geometric similarity of a Si channel and a PDMS mold, both of which were created through the anisotropic etching process of a single crystal Si, the microfluidic channel with the asymmetric cross-sectional shape and high HTWR was easily realized. The effects of HTWR of channels on the size and uniformity of generated micro-droplets were investigated. The monodisperse micro-droplets were generated as the HTWR of the asymmetric channel was over 3.5. In addition, it was found that the flow direction of the oil solution (continuous phase) affected the size of micro-droplets due to the asymmetric channel structures. Two kinds of monodisperse droplets with different sizes were successfully generated for a wider range of flow rates using the asymmetric channel structure in the developed microfluidic device.
Synthesis and Antimicrobial Activity of the Pathogenic E. coli Strains of p-Quinols: Additive Effects of Copper-Catalyzed Addition of Aryl Boronic Acid to Benzoquinones

A mild and efficient protocol for the synthesis of p-quinols under aqueous conditions was developed. The pivotal role of additives in the copper-catalyzed addition of aryl boronic and heteroaryl boronic acids to benzoquinones was observed. It was found that polyvinylpyrrolidone (PVP) was the most efficient additive used for the studied reaction. The noteworthy advantages of this procedure include its broad substrate scope, high yields up to 91%, atom economy, and usage of readily available starting materials. Another benefit of this method is the reusability of the catalytic system up to four times. Further, the obtained p-quinols were characterized on the basis of their antimicrobial activities against E. coli. Antimicrobial activity was further compared with the corresponding 4-benzoquinones and 4-hydroquinones. Among tested compounds, seven derivatives showed an antimicrobial activity profile similar to that observed for commonly used antibiotics such as ciprofloxacin, bleomycin, and cloxacillin. In addition, the obtained p-quinols constitute a suitable platform for further modifications, allowing for a convenient change in their biological activity profile.
Multi-Step Extracellular Matrix Remodelling and Stiffening in the Development of Idiopathic Pulmonary Fibrosis

The extracellular matrix (ECM) of the lung is a filamentous network composed mainly of collagens, elastin, and proteoglycans that provides structural and physical support to its populating cells. Proliferation, migration and overall behaviour of those cells is greatly determined by micromechanical queues provided by the ECM. Lung fibrosis displays an aberrant increased deposition of ECM which likely changes filament organization and stiffens the ECM, thus upregulating the profibrotic profile of pulmonary cells. We have previously used AFM to assess changes in the Young’s Modulus (E) of the ECM in the lung. Here, we perform further ECM topographical, mechanical and viscoelastic analysis at the micro- and nano-scale throughout fibrosis development. Furthermore, we provide nanoscale correlations between topographical and elastic properties of the ECM fibres. Firstly, we identify a softening of the ECM after rats are instilled with media associated with recovery of mechanical homeostasis, which is hindered in bleomycin-instilled lungs. Moreover, we find opposite correlations between fibre stiffness and roughness in PBS- vs bleomycin-treated lung. Our findings suggest that changes in ECM nanoscale organization take place at different stages of fibrosis, with the potential to help identify pharmacological targets to hinder its progression.
siRNA-Mediated Timp1 Silencing Inhibited the Inflammatory Phenotype during Acute Lung Injury

Acute lung injury is a complex cascade process that develops in response to various damaging factors, which can lead to acute respiratory distress syndrome. Within this study, based on bioinformatics reanalysis of available full-transcriptome data of acute lung injury induced in mice and humans by various factors, we selected a set of genes that could serve as good targets for suppressing inflammation in the lung tissue, evaluated their expression in the cells of different origins during LPS-induced inflammation, and chose the tissue inhibitor of metalloproteinase Timp1 as a promising target for suppressing inflammation. We designed an effective chemically modified anti-TIMP1 siRNA and showed that Timp1 silencing correlates with a decrease in the pro-inflammatory cytokine IL6 secretion in cultured macrophage cells and reduces the severity of LPS-induced acute lung injury in a mouse model.
Quantum fluctuations in chains of Josephson junctions

We study the effect of quantum fluctuations of the phase on the low-temperature behavior of two models of Josephson junction chains with Coulomb interactions taken into account. The first model, which represents a chain of junctions close to a ground plane, is the Hamiltonian version of the two-dimensional XY model in one space and one time dimension. We demonstrate explicitly how the Nelson-Kosterlitz jump manifests itself in the conduction properties of this system at a critical value of the superconducting grain capacitance. In the second model, the charging energy for a single junction in the chain is just the parallel-plate capacitor energy Q/sup 2//8C, where Q is the charge difference across the junction and C is its capacitance. We show that for any nonzero charging energy (i.e., C
Biglycan Involvement in Heart Fibrosis: Modulation of Adenosine 2A Receptor Improves Damage in Immortalized Cardiac Fibroblasts

Cardiac fibrosis is a common pathological feature of different cardiovascular diseases, characterized by the aberrant deposition of extracellular matrix (ECM) proteins in the cardiac interstitium, myofibroblast differentiation and increased fibrillar collagen deposition stimulated by transforming growth factor (TGF)-β activation. Biglycan (BGN), a small leucine-rich proteoglycan (SLRPG) integrated within the ECM, plays a key role in matrix assembly and the phenotypic control of cardiac fibroblasts. Moreover, BGN is critically involved in pathological cardiac remodeling through TGF-β binding, thus causing myofibroblast differentiation and proliferation. Adenosine receptors (ARs), and in particular A2AR, may play a key role in stimulating fibrotic damage through collagen production/deposition, as a consequence of cyclic AMP (cAMP) and AKT activation. For this reason, A2AR modulation could be a useful tool to manage cardiac fibrosis in order to reduce fibrotic scar deposition in heart tissue. Therefore, the aim of the present study was to investigate the possible crosstalk between A2AR and BGN modulation in an in vitro model of TGF-β-induced fibrosis. Immortalized human cardiac fibroblasts (IM-HCF) were stimulated with TGF-β at the concentration of 10 ng/mL for 24 h to induce a fibrotic phenotype. After applying the TGF-β stimulus, cells were treated with two different A2AR antagonists, Istradefylline and ZM241385, for an additional 24 h, at the concentration of 10 µM and 1 µM, respectively. Both A2AR antagonists were able to regulate the oxidative stress induced by TGF-β through intracellular reactive oxygen species (ROS) reduction in IM-HCFs. Moreover, collagen1a1, MMPs 3/9, BGN, caspase-1 and IL-1β gene expression was markedly decreased following A2AR antagonist treatment in TGF-β-challenged human fibroblasts. The results obtained for collagen1a1, SMAD3, α-SMA and BGN were also confirmed when protein expression was evaluated; phospho-Akt protein levels were also reduced following Istradefylline and ZM241385 use, thus suggesting that collagen production involves AKT recruited by the A2AR. These results suggest that A2AR modulation might be an effective therapeutic option to reduce the fibrotic processes involved in heart pathological remodeling.
DDR1 and Its Ligand, Collagen IV, Are Involved in In Vitro Oligodendrocyte Maturation

Discoidin domain receptor 1 (DDR1) is a tyrosine kinase receptor expressed in epithelial cells from different tissues in which collagen binding activates pleiotropic functions. In the brain, DDR1 is mainly expressed in oligodendrocytes (OLs), the function of which is unclear. Whether collagen can activate DDR1 in OLs has not been studied. Here, we assessed the expression of DDR1 during in vitro OL differentiation, including collagen IV incubation, and the capability of collagen IV to induce DDR1 phosphorylation. Experiments were performed using two in vitro models of OL differentiation: OLs derived from adult rat neural stem cells (NSCs) and the HOG16 human oligodendroglial cell line. Immunocytofluorescence, western blotting, and ELISA were performed to analyze these questions. The differentiation of OLs from NSCs was addressed using oligodendrocyte transcription factor 2 (Olig2) and myelin basic protein (MBP). In HOG16 OLs, collagen IV induced DDR1 phosphorylation through slow and sustained kinetics. In NSC-derived OLs, DDR1 was found in a high proportion of differentiating cells (MBP+/Olig2+), but its protein expression was decreased in later stages. The addition of collagen IV did not change the number of DDR1+/MBP+ cells but did accelerate OL branching. Here, we provide the first demonstration that collagen IV mediates the phosphorylation of DDR1 in HOG16 cells and that the in vitro co-expression of DDR1 and MBP is associated with accelerated branching during the differentiation of primary OLs.
Relationship between Objective and Subjective Fatigue Monitoring Tests in Professional Soccer

Studying fatigue is challenging because it is influenced by physiological, psychological, and sociological states. Fatigue can be assessed objectively or subjectively, but the literature has difficulty understanding how an analytical test relates to a response via a questionnaire. Thus, the purpose of this study was to evaluate the relationships between objective fatigue variables (Squat Jump (SJ) and Countermovement Jump (CMJ)) measured on day-2 to the game and subjective fatigue (Rating Perceived Exertion (RPE) measured on day-3 to the game and Hooper Index (HI) measured on day-2). The sample comprised 32 professional football players from the First Portuguese League aged 25.86 ± 3.15 years. The Spearman correlations and regression analyses were used to study the relationships between the variables. The results showed statistically significant (p < 0.05) but small correlations (0.113–0.172) between several objective metrics and the subjective metrics evaluated. In addition, we found two weak models with statistical significance (p < 0.05) between the dependent objective variables (contact time, height, and elasticity index) and the HI (R2 = 3.7%) and RPE (R2 = 1.6%). Also, nine statistically significant (p < 0.05) but weak models were observed between the subjective dependent variables (HI and RPE) and contact time (R2 = 1.8–2.7%), flight time (R2 = 1.1–1.9%), height (R2 = 1.2–2.3%), power (R2 = 1.4%), pace (R2 = 1.2–2.1%), and elasticity index (R2 = 1.6%). In conclusion, objective and subjective fatigue-monitoring tests in professional soccer do not measure identical but rather complementary aspects of fatigue, and therefore, both need to be considered to gain a holistic perspective.
Sacubitril/Valsartan in Heart Failure with Reduced Ejection Fraction: Real-World Experience from Italy (the REAL.IT Study)

Sacubitril/valsartan reduces heart failure (HF)-related hospitalizations and cardiovascular mortality in PARADIGM-HF and has become a foundational treatment for HF with reduced ejection fraction (HFrEF). However, data of its routine real-world use are limited, and evidence from Italian settings is lacking. The REAL.IT study aimed to characterize the demographics, pharmacotherapy, clinical characteristics and outcomes of sacubitril/valsartan-treated Italian patients with HFrEF. Electronic medical records of patients initiating sacubitril/valsartan from October 2016 to June 2019 at nine specialized hospital outpatient HF centers across Italy were reviewed. Overall, 924 adults (mean age 64.5 years, 84.6% male) were included. At baseline, 38.7% had an ischemic HF etiology, 45.9% hypertension, 23.2% atrial fibrillation, 25.4% diabetes mellitus, 26.1% an implantable cardioverter-defibrillator and 31.9% coronary artery bypass grafting. There were no clear patterns of patient selection over time. During follow-up, NYHA class improved in 37.5% of patients after a mean of 5.3 ± 3.8 months; 36.1% and 16.7% of patients were in NYHA class III during characterization and after one year of follow-up, respectively. Left ventricular ejection fraction (LVEF) improved ≥5% in 56.3% of patients at one year; 39.7% had ≥30% reduction of N-terminal pro-B-type natriuretic peptide; 2.2% had hyperkalemia during characterization and 2.6% during follow-up; and 3.8% had hypotension during characterization and 12% during follow-up. A total of 50 (5.8%) of patients had device implantation (ICD/CRT) during follow-up. HF-related hospitalization was recorded in 19.6% of patients during follow-up; 3.8% of patients died, approximately 1.3% from cardiovascular causes. Our real-world data confirm the favorable effectiveness and tolerability of sacubitril/valsartan observed in pivotal randomized controlled trials.
A Clinical, Pathological, Epidemiological and Molecular Investigation of Recent Outbreaks of Peste des Petits Ruminants Virus in Domestic and Wild Small Ruminants in the Abu Dhabi Emirate, United Arab Emirates

Simple Summary Peste des petits ruminants (PPR) is a contagious disease in domestic small ruminants. The virus can also infect wildlife, with unknown roles in PPR epidemiology. In the United Arab Emirates (UAE), the previously published reports were from wildlife only. This is a first report from the UAE describing PPRV in domestic small ruminants. From four outbreak notifications, the disease is investigated by clinical, pathological, and molecular studies. We found that the clinical and pathological forms of the disease were almost identical in all examined animals and compliant to the classical forms of the disease. Phylogenetic analysis based on the N gene and F gene classified the virus within Asian lineage IV. Abstract (1) Background: Peste des petits ruminants (PPR) is a highly contagious animal disease affecting small ruminants, leading to significant economic losses. There has been little published data on PPR virus (PPRV) infection in the United Arab Emirates (UAE); (2) Methods: four outbreaks reported in goats and Dama gazelle in 2021 were investigated using pathological and molecular testing; (3) Results: The infected animals showed symptoms of dyspnea, oculo-nasal secretions, cough, and diarrhea. Necropsy findings were almost similar in all examined animals and compliant to the classical forms of the disease. Phylogenetic analysis based on N gene and F gene partial sequences revealed a circulation of PPRV Asian lineage IV in the UAE, and these sequences clustered close to the sequences of PPRV from United Arab Emirates, Pakistan, Tajikistan and Iran; (4) Conclusions: PPRV Asian lineage IV is currently circulating in the UAE. To the best of our knowledge, this is a first study describing PPRV in domestic small ruminant in the UAE.