Miracle-dz/UniFAR-FTUs huggingface dataset:
Platelet-Rich Plasma Promotes the Proliferation of Human Keratinocytes via a Progression of the Cell Cycle. A Role of Prolidase

Although the role of platelet-rich plasma (PRP) in tissue regeneration has been confirmed in many studies, the mechanism of this process is still not fully understood. Human keratinocytes (HaCaT) cells were used as an experimental model for studies on the effects of PRP on cell proliferation, migration, collagen biosynthesis, prolidase activity, and its expression and anabolic signaling. The activation of epidermal growth factor receptor (EGFR), β1-integrin, and insulin-like growth factor-1 receptor (IGF-1R) by PRP were investigated by western blot and immunocytochemistry. It has been found that PRP induced keratinocytes migration and proliferation through activation of cell cycle progression and EGFR downstream signaling. Similar biological effects were achieved by an addition to the culture medium of prolidase (PEPD), a ligand of EGFR (PRP is a rich source of PEPD–2 ng/mL). PRP-dependent stimulation of collagen biosynthesis was accompanied by an increase in the expression of NF-κβ, IGF-1R-downstream signaling proteins, and PEPD activity. The data suggest that PRP activates a complex of growth factors and adhesion receptors that stimulate cell proliferation, migration, and collagen biosynthesis. PRP induces PEPD-dependent human keratinocyte proliferation through activation of the EGFR receptor. Our study provides a novel mechanism of PRP-dependent wound healing.
Construction of Inorganic Bulks through Coalescence of Particle Precursors

Bulk inorganic materials play important roles in human society, and their construction is commonly achieved by the coalescence of inorganic nano- or micro-sized particles. Understanding the coalescence process promotes the elimination of particle interfaces, leading to continuous bulk phases with improved functions. In this review, we mainly focus on the coalescence of ceramic and metal materials for bulk construction. The basic knowledge of coalescent mechanism on inorganic materials is briefly introduced. Then, the properties of the inorganic precursors, which determine the coalescent behaviors of inorganic phases, are discussed from the views of particle interface, size, crystallinity, and orientation. The relationships between fundamental discoveries and industrial applications are emphasized. Based upon the understandings, the applications of inorganic bulk materials produced by the coalescence of their particle precursors are further presented. In conclusion, the challenges of particle coalescence for bulk material construction are presented, and the connection between recent fundamental findings and industrial applications is highlighted, aiming to provide an insightful outlook for the future development of functional inorganic materials.
P2X7 Variants in Oncogenesis

The P2X7 receptor for extracellular ATP is a well-established mediator of tumoral development and progression both in solid cancers and hematological malignancies. The human P2X7 gene is highly polymorphic, and several splice variants of the receptor have been identified in time. P2X7 single-nucleotide polymorphisms (SNPs) have been broadly analyzed by studies relating them to pathologies as different as infectious, inflammatory, nervous, and bone diseases, among which cancer is included. Moreover, in the last years, an increasing number of reports concentrated on P2X7 splice variants’ different roles and their implications in pathological conditions, including oncogenesis. Here, we give an overview of established and recent literature demonstrating a role for human P2X7 gene products in oncological conditions, mainly focusing on current data emerging on P2X7 isoform B and nfP2X7. We explored the role of these and other genetic variants of P2X7 in cancer insurgence, dissemination, and progression, as well as the effect of chemotherapy on isoforms expression. The described literature strongly suggests that P2X7 variants are potential new biomarkers and therapeutical targets in oncological conditions and that their study in carcinogenesis deserves to be further pursued.
Estimating a Stoichiometric Solid’s Gibbs Free Energy Model by Means of a Constrained Evolutionary Strategy

Modeling of thermodynamic properties, like heat capacities for stoichiometric solids, includes the treatment of different sources of data which may be inconsistent and diverse. In this work, an approach based on the covariance matrix adaptation evolution strategy (CMA-ES) is proposed and described as an alternative method for data treatment and fitting with the support of data source dependent weight factors and physical constraints. This is applied to a Gibb’s Free Energy stoichiometric model for different magnesium sulfate hydrates by means of the NASA9 polynomial. Its behavior is proved by: (i) The comparison of the model to other standard methods for different heat capacity data, yielding a more plausible curve at high temperature ranges; (ii) the comparison of the fitted heat capacity values of MgSO4·7H2O against DSC measurements, resulting in a mean relative error of a 0.7% and a normalized root mean square deviation of 1.1%; and (iii) comparing the Van’t Hoff and proposed Stoichiometric model vapor-solid equilibrium curves to different literature data for MgSO4·7H2O, MgSO4·6H2O, and MgSO4·1H2O, resulting in similar equilibrium values, especially for MgSO4·7H2O and MgSO4·6H2O. The results show good agreement with the employed data and confirm this method as a viable alternative for fitting complex physically constrained data sets, while being a potential approach for automatic data fitting of substance data.
Clinical patterns of third nerve palsies in diabetic patients.

BACKGROUND Neuropathy is a frequent complication in diabetic patients with variable clinical presentations and evolutions. AIM The purpose of the study was to specify the clinical features of diabetic third nerve palsy, to assess the risk factors and to observe its evolution. METHODS We report a series of 11 diabetic patients with oculomotor paralysis collected in the department of endocrinology and diabetology of FarhatHached Hospital of Sousse between 1996 and 2005. RESULTS Our study was about 6 men and 5 women with an average age of 63.6 ± 13.7 years. All patients had type 2 diabetes. Eight patients presented with diplopia, three with periocular pain and 6 with headache. The oculomotor palsy was unilateral in all cases. All patients were in glycemic imbalance at the time of the diagnosis of ptosis and they were at high cardiovascular risk. The evolution under optimal equilibrium of diabetes and control of cardiovascular risk factors was marked by regression and disappearance in 4 patients, homo or contralateral recurrence in 4 patients and persistence of the palsy in 1 patient. CONCLUSION Glycemic equilibrium and ischemic phenomena due to cardiovascular risk factors are at the root of these oculomotor paralyses in diabetic patients. The evolution of diabetic mononevritis remains unpredictable despite the control of blood glucose levels and cardiovascular risk factors.
Effects of rs958804 and rs7858836 single‐nucleotide polymorphisms of the ASTN2 gene on pain‐related phenotypes in patients who underwent laparoscopic colectomy and mandibular sagittal split ramus osteotomy

Opioids are widely used as effective analgesics, but opioid sensitivity varies widely among individuals. The underlying genetic and nongenetic factors are not fully understood. Based on the results of our previous genome‐wide association study, we investigated the effects of single nucleotide polymorphisms (SNPs) of the astrotactin 2 (ASTN2) gene on pain‐related phenotypes in surgical patients.
Multi-omics analysis to identify susceptibility genes for colorectal cancer.

Most genetic variants for colorectal cancer (CRC) identified in genome-wide association studies (GWAS) are located in intergenic regions, implying pathogenic dysregulations of gene expression. However, comprehensive assessments of target genes in CRC remain to be explored. We conducted a multi-omics analysis using transcriptome and/or DNA methylation data from the Genotype-Tissue Expression (GTEx), The Cancer Genome Atlas (TCGA), and the Colonomics projects. We identified 116 putative target genes for 45 GWAS-identified variants. Using summary-data-based Mendelian Randomization approach (SMR), we demonstrated that the CRC susceptibility for 29 out of the 45 CRC variants may be mediated by cis-effects on gene regulation. At a cutoff of the Bonferroni-corrected PSMR < 0.05, we determined 66 putative susceptibility genes, including 39 genes that have not been previously reported. We further performed in vitro assays for two selected genes, DIP2B and SFMBT1, and provide functional evidence that they play a vital role in colorectal carcinogenesis via disrupting cell behavior, including migration, invasion and epithelial-mesenchymal transition. Our study reveals a large number of putative novel susceptibility genes and provides additional insight into the underlying mechanisms for CRC genetic risk loci.
Real-Time Fluorescence Image-Guided Oncolytic Virotherapy for Precise Cancer Treatment

Oncolytic virotherapy is one of the most promising, emerging cancer therapeutics. We generated three types of telomerase-specific replication-competent oncolytic adenovirus: OBP-301; a green fluorescent protein (GFP)-expressing adenovirus, OBP-401; and Killer-Red-armed OBP-301. These oncolytic adenoviruses are driven by the human telomerase reverse transcriptase (hTERT) promoter; therefore, they conditionally replicate preferentially in cancer cells. Fluorescence imaging enables visualization of invasion and metastasis in vivo at the subcellular level; including molecular dynamics of cancer cells, resulting in greater precision therapy. In the present review, we focused on fluorescence imaging applications to develop precision targeting for oncolytic virotherapy. Cell-cycle imaging with the fluorescence ubiquitination cell cycle indicator (FUCCI) demonstrated that combination therapy of an oncolytic adenovirus and a cytotoxic agent could precisely target quiescent, chemoresistant cancer stem cells (CSCs) based on decoying the cancer cells to cycle to S-phase by viral treatment, thereby rendering them chemosensitive. Non-invasive fluorescence imaging demonstrated that complete tumor resection with a precise margin, preservation of function, and prevention of distant metastasis, was achieved with fluorescence-guided surgery (FGS) with a GFP-reporter adenovirus. A combination of fluorescence imaging and laser ablation using a KillerRed-protein reporter adenovirus resulted in effective photodynamic cancer therapy (PDT). Thus, imaging technology and the designer oncolytic adenoviruses may have clinical potential for precise cancer targeting by indicating the optimal time for administering therapeutic agents; accurate surgical guidance for complete resection of tumors; and precise targeted cancer-specific photosensitization.
Mechanisms of Dietary Sodium-Induced Impairments in Endothelial Function and Potential Countermeasures

Despite decades of efforts to reduce sodium intake, excess dietary sodium remains commonplace, and contributes to increased cardiovascular morbidity and mortality independent of its effects on blood pressure. An increasing amount of research suggests that high-sodium diets lead to reduced nitric oxide-mediated endothelial function, even in the absence of a change in blood pressure. As endothelial dysfunction is an early step in the progression of cardiovascular diseases, the endothelium presents a target for interventions aimed at reducing the impact of excess dietary sodium. In this review, we briefly define endothelial function and present the literature demonstrating that excess dietary sodium results in impaired endothelial function. We then discuss the mechanisms through which sodium impairs the endothelium, including increased reactive oxygen species, decreased intrinsic antioxidant defenses, endothelial cell stiffening, and damage to the endothelial glycocalyx. Finally, we present selected research findings suggesting that aerobic exercise or increased intake of dietary potassium may counteract the deleterious vascular effects of a high-sodium diet.
Systemic Risk: The Threat to Societal Diversity and Coherence

Insights from complexity science can be applied to the analysis of social processes in heterogeneous societies. Many features that characterize and influence complex structures in nearly every domain of nature, technology, and society can be derived from simple modeling processes in physics and chemistry. If one applies these features to the structure of social risks, a number of insights are gained that can be subject to further empirical analysis. In particular, they add—to the well‐known steering mechanisms of hierarchy, competition, and cooperation—the contribution of self‐organization, the effect of which is underestimated in almost all theories of social science. But in view of the crises facing modern democracy, such as migration and populism, it is precisely this mechanism of dynamic structure generation that is decisive for an effective and fair risk governance. In this article, we analyze the threat to societal diversity and coherence on the basis of complexity science.
Respiratory Syncytial Virus G Protein Sequence Variability among Isolates from St. Petersburg, Russia, during the 2013–2014 Epidemic Season

Human respiratory syncytial virus (RSV) is the most common cause of upper and lower respiratory tract infections in infants and young children. It is actively evolving under environmental and herd immunity influences. This work presents, for the first time, sequence variability analysis of RSV G gene and G protein using St. Petersburg (Russia) isolates. Viruses were isolated in a cell culture from the clinical samples of 61 children hospitalized (January–April 2014) with laboratory-confirmed RSV infection. Real-time RT-PCR data showed that 56 isolates (91.8%) belonged to RSV-A and 5 isolates (8.2%) belonged to RSV-B. The G genes were sequenced for 27 RSV-A isolates and all of them belonged to genotype ON1/GA2. Of these RSV-A, 77.8% belonged to the ON1(1.1) genetic sub-cluster, and 14.8% belonged to the ON1(1.2) sub-cluster. The ON1(1.3) sub-cluster constituted a minor group (3.7%). Many single-amino acid substitutions were identified in the G proteins of St. Petersburg isolates, compared with the Canadian ON1/GA2 reference virus (ON67-1210A). Most of the amino acid replacements were found in immunodominant B- and T-cell antigenic determinants of G protein. These may affect the antigenic characteristics of RSV and influence the host antiviral immune response to currently circulating viruses.
Decreased 18F-Fluorodeoxyglucose Uptake in Lumbar Vertebrae of Stroke Patients

Background and Purpose We investigated 18F-fluorodeoxyglucose (FDG) uptake levels in the lumbar vertebrae, liver, and spleen of stroke patients with carotid atherosclerosis. Methods This study analyzed acute ischemic stroke patients with carotid atherosclerosis who underwent whole-body FDG positron-emission tomography between October 2015 and January 2017. FDG uptake in the lumbar vertebrae, liver, and spleen was measured and compared between stroke patients and control subjects without stroke history. Multivariate linear regression analysis was performed to identify independent factors related to FDG uptake in the proximal internal carotid artery (ICA). Results Twenty stroke patients aged 75.1±9.0 years (mean±standard deviation; 10 females) and 20 control subjects aged 62.9±10.7 years (6 females) were included. In comparison with the control group, the stroke group showed significantly higher FDG uptake in the proximal ICA (1.16±0.26 vs. 0.87±0.19, p<0.01), but significantly lower FDG uptake in the lumbar vertebrae (1.09±0.26 vs. 1.38±0.38, p=0.007) and liver (1.71±0.30 vs. 2.01±0.34, p=0.005). Multivariate linear regression analysis showed that the lumbar FDG uptake was negatively correlated with FDG uptake in the proximal ICA (standardized coefficient=-0.367, p=0.013) after adjusting for age and hypertension. Conclusions Stroke patients showed decreased FDG uptake in the lumbar vertebrae. Further studies are warranted to evaluate the pathophysiological link between cerebral atherosclerosis and bone.
Costs of Point-of-Care Viral Load Testing for Adults and Children Living with HIV in Kenya

Background: The number of people living with HIV (PLHIV) in need of treatment monitoring in low-and-middle-income countries is rapidly expanding, straining existing laboratory capacity. Point-of-care viral load (POC VL) testing can alleviate the burden on centralized laboratories and enable faster delivery of results, improving clinical outcomes. However, implementation costs are uncertain and will depend on clinic testing volume. We sought to estimate the costs of decentralized POC VL testing compared to centralized laboratory testing for adults and children receiving HIV care in Kenya. Methods: We conducted microcosting to estimate the per-patient costs of POC VL testing compared to known costs of centralized laboratory testing. We completed time-and-motion observations and stakeholder interviews to assess personnel structures, staff time, equipment costs, and laboratory processes associated with POC VL administration. Capital costs were estimated using a 5 year lifespan and a 3% annual discount rate. Results: We estimated that POC VL testing cost USD $24.25 per test, assuming a clinic is conducting 100 VL tests per month. Test cartridge and laboratory equipment costs accounted for most of the cost (62% and 28%, respectively). Costs varied by number of VL tests conducted at the clinic, ranging from $54.93 to $18.12 per test assuming 20 to 500 VL tests per month, respectively. A VL test processed at a centralized laboratory was estimated to cost USD $25.65. Conclusion: POC VL testing for HIV treatment monitoring can be feasibly implemented in clinics within Kenya and costs declined with higher testing volumes. Our cost estimates are useful to policymakers in planning resource allocation and can inform cost-effectiveness analyses evaluating POC VL testing.
Combined relationship of physical inactivity and sedentary behaviour with the prevalence of noncommunicable chronic diseases: data from 52,675 Brazilian adults and elderly

ABSTRACT This paper aims to verify the association between the combined relationship of physical inactivity and sedentary behaviour (SB) at leisure-time and the prevalence of noncommunicable chronic diseases (NCDs) in Brazilian adults and elderly. This is a cross-sectional study, derived from the VIGITEL system, with individuals ≥18 years old (n = 52,675). The presence of NCDs (diabetes, hypertension, and obesity) and the independent variables were defined by self-report. Binary logistic regression was used. While adults with the presence of, at least, one risky behaviour had a higher odds to have obesity (OR active + high SB: 1.25; 95%CI: 1.01;1.54; OR inactive + low SB: 1.47; 95%CI: 1.25;1.73; OR inactive + high SB: 1.77; 95%CI: 1.47;2.12), the elderly had an increased risk for this outcome only when classified as inactive (OR inactive + low SB: 1.43; 95%CI: 1.17;1.75; OR inactive + high SB: 1.87; 95%CI: 1.47;2.38). Inactive adults with low SB were more likely to have diabetes (OR inactive + low SB: 1.31; 95%CI: 1.00;1.71) and hypertension (OR inactive + low SB: 1.26; 95%CI: 1.08;1.46), while physical inactivity was again more strongly associated with these outcomes in the elderly, for diabetes (OR inactive + low SB: 1.23; 95%CI: 1.02;1.48; OR inactive + high SB: 1.75; 95%CI: 1.39;2.19), and hypertension (OR inactive + low SB: 1.22; 95%CI: 1.05;1.41; OR inactive + high SB: 1.60; 95%CI: 1.33;1.94) Both leisure-time behaviours carry a high risk of the prevalence of different NCDs, however, physical inactivity, isolated or combined, showed a greater association with the evaluated outcomes. Highlights This cross-national survey included representative sample of people ≥18 years old. Adults with at least one evident risky behavior had a higher chance of obesity. Inactive adults with low sedentary behavior had higher chances for diabetes and hypertension. Physical inactivity was more strongly associated with all diseases in the elderly.
Defining the Cell Wall, Cell Cycle and Chromatin Landmarks in the Responses of Brachypodium distachyon to Salinity

Excess salinity is a major stress that limits crop yields. Here, we used the model grass Brachypodium distachyon (Brachypodium) reference line Bd21 in order to define the key molecular events in the responses to salt during germination. Salt was applied either throughout the germination period (“salt stress”) or only after root emergence (“salt shock”). Germination was affected at ≥100 mM and root elongation at ≥75 mM NaCl. The expression of arabinogalactan proteins (AGPs), FLA1, FLA10, FLA11, AGP20 and AGP26, which regulate cell wall expansion (especially FLA11), were mostly induced by the “salt stress” but to a lesser extent by “salt shock”. Cytological assessment using two AGP epitopes, JIM8 and JIM13 indicated that “salt stress” increases the fluorescence signals in rhizodermal and exodermal cell wall. Cell division was suppressed at >75 mM NaCl. The cell cycle genes (CDKB1, CDKB2, CYCA3, CYCB1, WEE1) were induced by “salt stress” in a concentration-dependent manner but not CDKA, CYCA and CYCLIN-D4-1-RELATED. Under “salt shock”, the cell cycle genes were optimally expressed at 100 mM NaCl. These changes were consistent with the cell cycle arrest, possibly at the G1 phase. The salt-induced genomic damage was linked with the oxidative events via an increased glutathione accumulation. Histone acetylation and methylation and DNA methylation were visualized by immunofluorescence. Histone H4 acetylation at lysine 5 increased strongly whereas DNA methylation decreased with the application of salt. Taken together, we suggest that salt-induced oxidative stress causes genomic damage but that it also has epigenetic effects, which might modulate the cell cycle and AGP expression gene. Based on these landmarks, we aim to encourage functional genomics studies on the responses of Brachypodium to salt.
Metabolomic and Transcriptomic Profiling Provide Novel Insights into Fruit Ripening and Ripening Disorder Caused by 1-MCP Treatments in Papaya

Treatment with 1-methylcyclopropylene (1-MCP) is an effective technique to preserve fruits, but inappropriate treatment with 1-MCP causes a ripening disorder (rubbery texture) in papaya fruit. In this study, a combined metabolomic and transcriptomic analysis was conducted to reveal the possible mechanism of the ripening disorder caused by unsuitable 1-MCP in papaya. A total of 203 differential accumulated metabolites (DAMs) were identified in the metabolome analysis. Only 24 DAMs were identified in the control (CK) vs. the 1-MCP 2 h group, and they were primarily flavonoids. Ninety and 89 DAMs were identified in the CK vs. 1-MCP 16 h and 1-MCP 2 h vs. 1-MCP 16 h groups, respectively, indicating that long-term 1-MCP treatment severely altered the metabolites during fruit ripening. 1-MCP 16 h treatment severely reduced the number of metabolites, which primarily consisted of flavonoids, lipids, phenolic acids, alkaloids, and organic acids. An integrated analysis of RNA-Seq and metabolomics showed that various energy metabolites for the tricarboxylic acid cycle were reduced by long-term treatment with 1-MCP, and the glycolic acid cycle was the most significantly affected, as well as the phenylpropane pathway. These results provide valuable information for fruit quality control and new insight into the ripening disorder caused by unsuitable treatment with 1-MCP in papaya.