Miracle-dz/UniFAR-FTUs huggingface dataset:
Predicting Mechanical Properties of High-Performance Fiber-Reinforced Cementitious Composites by Integrating Micromechanics and Machine Learning

Current development of high-performance fiber-reinforced cementitious composites (HPFRCC) mainly relies on intensive experiments. The main purpose of this study is to develop a machine learning method for effective and efficient discovery and development of HPFRCC. Specifically, this research develops machine learning models to predict the mechanical properties of HPFRCC through innovative incorporation of micromechanics, aiming to increase the prediction accuracy and generalization performance by enriching and improving the datasets through data cleaning, principal component analysis (PCA), and K-fold cross-validation. This study considers a total of 14 different mix design variables and predicts the ductility of HPFRCC for the first time, in addition to the compressive and tensile strengths. Different types of machine learning methods are investigated and compared, including artificial neural network (ANN), support vector regression (SVR), classification and regression tree (CART), and extreme gradient boosting tree (XGBoost). The results show that the developed machine learning models can reasonably predict the concerned mechanical properties and can be applied to perform parametric studies for the effects of different mix design variables on the mechanical properties. This study is expected to greatly promote efficient discovery and development of HPFRCC.
Human Granulosa Cells—Stemness Properties, Molecular Cross-Talk and Follicular Angiogenesis

The ovarian follicle is the basic functional unit of the ovary, comprising theca cells and granulosa cells (GCs). Two different types of GCs, mural GCs and cumulus cells (CCs), serve different functions during folliculogenesis. Mural GCs produce oestrogen during the follicular phase and progesterone after ovulation, while CCs surround the oocyte tightly and form the cumulus oophurus and corona radiata inner cell layer. CCs are also engaged in bi-directional metabolite exchange with the oocyte, as they form gap-junctions, which are crucial for both the oocyte’s proper maturation and GC proliferation. However, the function of both GCs and CCs is dependent on proper follicular angiogenesis. Aside from participating in complex molecular interplay with the oocyte, the ovarian follicular cells exhibit stem-like properties, characteristic of mesenchymal stem cells (MSCs). Both GCs and CCs remain under the influence of various miRNAs, and some of them may contribute to polycystic ovary syndrome (PCOS) or premature ovarian insufficiency (POI) occurrence. Considering increasing female fertility problems worldwide, it is of interest to develop new strategies enhancing assisted reproductive techniques. Therefore, it is important to carefully consider GCs as ovarian stem cells in terms of the cellular features and molecular pathways involved in their development and interactions as well as outline their possible application in translational medicine.
Severe COVID-19 in Hospitalized Carriers of Single CFTR Pathogenic Variants

The clinical presentation of COVID-19 is extremely heterogeneous, ranging from asymptomatic to severely ill patients. Thus, host genetic factors may be involved in determining disease presentation and progression. Given that carriers of single cystic fibrosis (CF)-causing variants of the CFTR gene—CF-carriers—are more susceptible to respiratory tract infections, our aim was to determine their likelihood of undergoing severe COVID-19. We implemented a cohort study of 874 individuals diagnosed with COVID-19, during the first pandemic wave in Italy. Whole exome sequencing was performed and validated CF-causing variants were identified. Forty subjects (16 females and 24 males) were found to be CF-carriers. Among mechanically ventilated patients, CF-carriers were more represented (8.7%) and they were significantly (p < 0.05) younger (mean age 51 years) compared to noncarriers (mean age 61.42 years). Furthermore, in the whole cohort, the age of male CF-carriers was lower, compared to noncarriers (p < 0.05). CF-carriers had a relative risk of presenting an abnormal inflammatory response (CRP ≥ 20 mg/dL) of 1.69 (p < 0.05) and their hazard ratio of death at day 14 was 3.10 (p < 0.05) in a multivariate regression model, adjusted for age, sex and comorbidities. In conclusion, CF-carriers are more susceptible to the severe form of COVID-19, showing also higher risk of 14-day death.
Examining the Correlates of Adolescent Food and Nutrition Knowledge

Food literacy is a set of skills and knowledge that are integral to diet. It is common among teenagers to not have basic food literacy skills needed to consume a healthy diet. This study examined: (1) the current state of food and nutrition knowledge among adolescents 13–19 years of age in the census metropolitan area of London, ON, Canada; and (2) correlates of food knowledge and nutrition knowledge among adolescents. Data for this study were drawn from baseline youth and parent survey data collected from a larger population health intervention study. Statistical analysis of the survey data indicates that higher parental education and higher median neighbourhood family income, the use of mobile health applications, liking to cook, as well as confidence in reading and understanding food labels were all consistently associated with increased food and nutrition knowledge. Findings may help guide future research towards optimal methods for delivering food literacy interventions to effectively educate teenagers. Results of this study may help guide policy makers, researchers, and public health professionals in developing appropriate food and nutrition programs and curriculums to combat the decline in food literacy skills.
Efficacy and Selectivity of FGF2-Saporin Cytosolically Delivered by PCI in Cells Overexpressing FGFR1

Fibroblast growth factor receptors (FGFRs) have become an attractive target in cancer research and therapy due to their implication in several cancers. Limitations of current treatment options require a need for additional, more specific and potent strategies to overcome cancers driven by FGFRs. Photochemical internalization (PCI) is a light-controlled method for cytosolic delivery of drugs that are entrapped in endosomes and lysosomes. We here evaluated the efficacy and selectivity of PCI of FGF2-saporin (FGF-SAP) in cells overexpressing FGFR1. FGF-SAP is a conjugate of FGF2 and the highly cytotoxic ribosome-inactivating protein (RIP) saporin, which is used as payload to eliminate cancer cells. Evaluation of the targeting effect of PCI of FGF-SAP was done by comparing the cytotoxic response in osteosarcoma cells with very low levels of FGFR1 (U2OS) to cells overexpressing FGFR1 (U2OS-R1). We demonstrate that PCI greatly enhances cytotoxicity of the drug showing efficient cell killing at pM concentrations of the drug in U2OS-R1 cells. However, U2OS cells were also sensitive to the toxin after PCI. Binding experiments using confocal microscopy and Western blotting techniques indicate that FGF-SAP is taken up by cells through heparan sulfate proteoglycans (HSPGs) in U2OS cells. We further show that the cytotoxicity of FGF-SAP in U2OS cells was reduced when cells were co-treated with heparin to compete out binding to HSPG, demonstrating that the cytotoxic effect was due to internalization by HSPGs. We conclude that to prevent off-target effects of FGF-based toxins, it will be necessary to circumvent binding to HSPGs, for example by mutating the binding site of FGF2 to HSPGs.
Role of Perivascular Adipose Tissue-Derived Adiponectin in Vascular Homeostasis

Studies of adipose tissue biology have demonstrated that adipose tissue should be considered as both passive, energy-storing tissue and an endocrine organ because of the secretion of adipose-specific factors, called adipokines. Adiponectin is a well-described homeostatic adipokine with metabolic properties. It regulates whole-body energy status through the induction of fatty acid oxidation and glucose uptake. Adiponectin also has anti-inflammatory and antidiabetic properties, making it an interesting subject of biomedical studies. Perivascular adipose tissue (PVAT) is a fat depot that is conterminous to the vascular wall and acts on it in a paracrine manner through adipokine secretion. PVAT-derived adiponectin can act on the vascular wall through endothelial cells and vascular smooth muscle cells. The present review describes adiponectin’s structure, receptors, and main signaling pathways. We further discuss recent studies of the extent and nature of crosstalk between PVAT-derived adiponectin and endothelial cells, vascular smooth muscle cells, and atherosclerotic plaques. Furthermore, we argue whether adiponectin and its receptors may be considered putative therapeutic targets.
Target Therapies for NASH/NAFLD: From the Molecular Aspect to the Pharmacological and Surgical Alternatives

Non-alcoholic fatty liver disease represents an increasing cause of chronic hepatic disease in recent years. This condition usually arises in patients with multiple comorbidities, the so-called metabolic syndrome. The therapeutic options are multiple, ranging from lifestyle modifications, pharmacological options, to liver transplantation in selected cases. The choice of the most beneficial one and their interactions can be challenging. It is mandatory to stratify the patients according to the severity of their disease to tailor the available treatments. In our contribution, we review the most recent pharmacological target therapies, the role of bariatric surgery, and the impact of liver transplantation on the NAFLD outcome.
Modulation of Organogenesis and Somatic Embryogenesis by Ethylene: An Overview

Ethylene is a plant hormone controlling physiological and developmental processes such as fruit maturation, hairy root formation, and leaf abscission. Its effect on regeneration systems, such as organogenesis and somatic embryogenesis (SE), has been studied, and progress in molecular biology techniques have contributed to unveiling the mechanisms behind its effects. The influence of ethylene on regeneration should not be overlooked. This compound affects regeneration differently, depending on the species, genotype, and explant. In some species, ethylene seems to revert recalcitrance in genotypes with low regeneration capacity. However, its effect is not additive, since in genotypes with high regeneration capacity this ability decreases in the presence of ethylene precursors, suggesting that regeneration is modulated by ethylene. Several lines of evidence have shown that the role of ethylene in regeneration is markedly connected to biotic and abiotic stresses as well as to hormonal-crosstalk, in particular with key regeneration hormones and growth regulators of the auxin and cytokinin families. Transcriptional factors of the ethylene response factor (ERF) family are regulated by ethylene and strongly connected to SE induction. Thus, an evident connection between ethylene, stress responses, and regeneration capacity is markedly established. In this review the effect of ethylene and the way it interacts with other players during organogenesis and somatic embryogenesis is discussed. Further studies on the regulation of ERF gene expression induced by ethylene during regeneration can contribute to new insights on the exact role of ethylene in these processes. A possible role in epigenetic modifications should be considered, since some ethylene signaling components are directly related to histone acetylation.
Molecular Cloning and Functional Characterization of Three 5-HT Receptor Genes (HTR1B, HTR1E, and HTR1F) in Chickens

The serotonin (5-hydroxytryptamine, 5-HT) signaling system is involved in a variety of physiological functions, including the control of cognition, reward, learning, memory, and vasoconstriction in vertebrates. Contrary to the extensive studies in the mammalian system, little is known about the molecular characteristics of the avian serotonin signaling network. In this study, we cloned and characterized the full-length cDNA of three serotonin receptor genes (HTR1B, HTR1E and HTR1F) in chicken pituitaries. Synteny analyses indicated that HTR1B, HTR1E and HTR1F were highly conserved across vertebrates. Cell-based luciferase reporter assays showed that the three chicken HTRs were functional, capable of binding their natural ligands (5-HT) or selective agonists (CP94253, BRL54443, and LY344864) and inhibiting intracellular cAMP production in a dose-dependent manner. Moreover, activation of these receptors could stimulate the MAPK/ERK signaling cascade. Quantitative real-time PCR analyses revealed that HTR1B, HTR1E and HTR1F were primarily expressed in various brain regions and the pituitary. In cultured chicken pituitary cells, we found that LY344864 could significantly inhibit the secretion of PRL stimulated by vasoactive intestinal peptide (VIP) or forskolin, revealing that HTR1F might be involved in the release of prolactin in chicken. Our findings provide insights into the molecular mechanism and facilitate a better understanding of the serotonergic modulation via HTR1B, HTR1E and HTR1F in avian species.
Refractory Dry Eye Syndrome after Transconjunctival Excision of the Palpebral Lobe of the Lacrimal Gland

The aim of the present study was to report two cases of refractory dry eye syndrome (DES) after transconjunctival excision of the palpebral lobe of the lacrimal gland. A 25-year-old female patient with a chief complaint of a palpable mass in both upper eyelids visited our medical center. Preoperative orbital computer tomography showed high-attenuation lesions in both lacrimal glands. Incisional biopsy of the lacrimal gland palpebral lobe via transconjunctival incision was performed in January 2019. At 1 month after the biopsy, a lack of tears and persistent corneal erosions were found in both eyes. Artificial tears, punctal occlusion, autologous serum eye drops, and therapeutic contact lenses were applied in an attempt to control the dry eye symptoms. The patient continues to suffer from intractable DES at 2.5 years after the procedure. The second case involved a 52-year-old female patient who visited our medical center with a chief complaint of a palpable mass in both upper eyelids. Bilateral orbital tumors were diagnosed with preoperative magnetic resonance imaging. An incisional biopsy of the lacrimal gland was performed. Immunoglobulin G4-related dacryoadenitis was confirmed through lacrimal palpebral lobe incisional biopsy. Intractable DES and corneal erosion of her left eye persisted thereafter. A transconjunctival incision is an effective approach for minimizing postoperative scars and is suitable for the biopsy of tumors that are visible through the conjunctiva. After a biopsy of the palpebral lobe of the main lacrimal glands, the secretion of reflex tears decreases due to damage to the secreting ducts of the main lacrimal glands. However, total tear secretion can be maintained by basal tear secretion from the accessory lacrimal glands. In this report, we describe two cases of refractory DES due to decreased total tear secretion, although only the palpebral lobes of the main lacrimal glands were biopsied.
Beneficial Effects of Mineralocorticoid Receptor Pathway Blockade against Endothelial Inflammation Induced by SARS-CoV-2 Spike Protein

Background: Vascular endothelial cells activation and dysfunction mediate inflammation and abnormal coagulation in COVID-19 patients. Mineralocorticoid receptor (MR) signaling and its downstream target Galectin-3 (Gal-3) are known to mediate cardiovascular inflammation and might be involved in the pathogenesis of COVID-19 complications. Accordingly, we aimed to investigate the potential beneficial effects of MR antagonism and Gal-3 inhibition on the inflammatory response induced by SARS-CoV-2 Spike protein in human aortic endothelial cells (HAECs). Methods: HAECs were treated with recombinant SARS-COV2 Spike (S) protein. MR antagonists (namely spironolactone and eplerenone) or the Gal-3 inhibitor G3P-01 were supplemented before and after S protein challenge. HAECs supernatants were assessed by ELISA or Western blotting. Results: HAECs treated with recombinant S protein resulted in enhanced secretion of inflammatory molecules (interleukin-6, monocyte chemoattractant protein-1, interleukin-18, interleukin-27, and interferon-γ) as well as in the thrombosis marker plasminogen activator inhibitor (PAI)-1. This was prevented and reversed by both MR antagonists and G3P-01. Conclusions: These findings indicate that MR/Gal-3 pathway blockade could be a promising option to reduce endothelial inflammation in SARS-CoV-2 infection.
A Novel Signature of CCNF-Associated E3 Ligases Collaborate and Counter Each Other in Breast Cancer

Simple Summary The dysregulation of UPS exacerbates the tumor microenvironment and drives malignant transformation. As the largest family of E3 ligases, the SCFF-boxes promotes BRCA progression. FBXL8 was recently identified to be a novel SCF E3 ligase that potently promotes BRCA. Here, we profiled the transcriptome of BRCA patient tissues by global NGS RNA-Seq and TCGA database analyses. A signature of four SCFF-box E3 ligases (FBXL8, FBXO43, FBXO15, CCNF) was found to be pivotal for BRCA advancement. Knockdown of FBXL8 and FBXO43 reduced cancer cell viability and proliferation, suggesting their pro-tumorigenic roles. However, the overexpression of CCNF inhibited cancer cell progression, indicating its anti-tumorigenic role. FBXL8 and FZR1 pulled down CCNF, and double knockdown of FBXL8 and FZR1 caused CCNF accumulation. Additionally, CCNF partnered with a pro-tumorigenic factor, RRM2, and overexpression of CCNF reduced RRM2. Our findings suggest a potential for drugging CCNF in co-modulatory partnership with FBXL8 and FZR1, for anti-BRCA therapy. Abstract Breast cancer (BRCA) malignancy causes major fatalities amongst women worldwide. SCF (Skp1-cullin-F-box proteins) E3 ubiquitin ligases are the most well-known members of the ubiquitination–proteasome system (UPS), which promotes cancer initiation and progression. Recently, we demonstrated that FBXL8, a novel F-box protein (SCFF-boxes) of SCF E3 ligase, accelerates BRCA advancement and metastasis. Since SCFF-boxes is a key component of E3 ligases, we hypothesized that other SCFF-boxes besides FBXL8 probably collaborate in regulating breast carcinogenesis. In this study, we retrospectively profiled the transcriptome of BRCA tissues and found a notable upregulation of four SCFF-box E3 ligases (FBXL8, FBXO43, FBXO15, and CCNF) in the carcinoma tissues. Similar to FBXL8, the knockdown of FBXO43 reduced cancer cell viability and proliferation, suggesting its pro-tumorigenic role. The overexpression of CCNF inhibited cancer cell progression, indicating its anti-tumorigenic role. Unexpectedly, CCNF protein was markedly downregulated in BRCA tissues, although its mRNA level was high. We showed that both E3 ligases, FBXL8 and FZR1, pulled down CCNF. Double knockdown of FBXL8 and FZR1 caused CCNF accumulation. On the other hand, CCNF itself pulled down a tumorigenic factor, RRM2, and CCNF overexpression reduced RRM2. Altogether, we propose a signature network of E3 ligases that collaboratively modulates CCNF anti-cancer activity. There is potential to target BRCA through modulation of the partnership axes of (i) CCNF-FBXL8, (ii) CCNF-FZR1, and (iii) CCNF-RRM2, particularly, via CCNF overexpression and activation and FBXL8/FZR1 suppression.
Relationship between Psychological Distress and Prolonged Sedentary Bouts in the Elderly: Four Period Analysis

Background: Too much sitting is associated with low mental health in elderly individuals. We clarified the relationship between psychological distress and the rate of prolonged sedentary bouts (PSBs) among the elderly over four periods. Methods: In a secondary analysis, a sample population of 68 adults aged 65 years or older in Japan was used. The following proxy variables were used: PSB (mental health) and the Kessler 6 scale; K6 scores (psychological distress). Results: Using the cross-lagged effects models, from “2016 K6” to “2017 PSB” (p = 0.004), from “2017 K6” to “2018 PSB” (p < 0.001), and from “2018 K6” to “2019 PSB” (p = 0.021) were all significant; however, the reverse were not all significant in one period. In four periods, from “2016 PSB” to “2019 K6” (p = 0.025) was significant; however, the reverse was not significant. Fit indices were obtained: χ2 = 7.641 (p = 0.182), goodness of fit index (GFI) = 0.891, comparative fit index (CFI) = 0.901, and root mean square error of approximation (RMSEA) = 0.121 in structural equation modelling. Conclusions: Psychological distress may affect the rate of PSB after one year, and the rate of PSB may affect the rate of psychological distress after three years in elderly individuals.
Appropriate Antibiotic Use and Associated Factors in Vietnamese Outpatients

Background: Inappropriate antibiotic use among outpatients is recognized as the primary driver of antibiotic resistance. A proper understanding of appropriate antibiotic usage and associated factors helps to determine and limit inappropriateness. We aimed to identify the rate of appropriate use of antibiotics and identify factors associated with the inappropriate prescriptions. Methods: We conducted a cross-sectional descriptive study in outpatient antibiotic use at a hospital in Can Tho City, Vietnam, from August 1, 2019, to January 31, 2020. Data were extracted from all outpatient prescriptions at the Medical Examination Department and analyzed by SPSS 18 and Chi-squared tests, with 95% confidence intervals. The rationale for antibiotic use was evaluated through antibiotic selection, dose, dosing frequency, dosing time, interactions between antibiotics and other drugs, and general appropriate usage. Results: A total of 420 prescriptions were 51.7% for females, 61.7% with health insurance, and 44.0% for patients with one comorbid condition. The general appropriate antibiotic usage rate was 86.7%. Prescriptions showed that 11.0% and 9.5% had a higher dosing frequency and dose than recommended, respectively; 10.2% had an inappropriate dosing time; 3.1% had drug interactions; and only 1.7% had been prescribed inappropriate antibiotics. The risk of inappropriate antibiotic use increased in patients with comorbidities and antibiotic treatment lasting >7 days (p < 0.05). Conclusions: The study indicated a need for more consideration when prescribing antibiotics to patients with comorbidities or using more than 7 days of treatment.