Miracle-dz/UniFAR-FTUs huggingface dataset:
Chronic Sildenafil Treatment Improves Vasomotor Function in a Mouse Model of Accelerated Aging

Aging leads to a loss of vasomotor control. Both vasodilation and vasoconstriction are affected. Decreased nitric oxide–cGMP-mediated relaxation is a hallmark of aging. It contributes to vascular disease, notably hypertension, infarction, and dementia. Decreased vasodilation can be caused by aging independently from cardiovascular risk factors. This process that can be mimicked in mice in an accelerated way by activation of the DNA damage response. Genetic deletion of the DNA repair enzyme ERCC1 endonuclease in mice, as in the case of Ercc1Δ/- mice, can be used as a tool to accelerate aging. Ercc1Δ/- mice develop age-dependent vasomotor dysfunction from two months after birth. In the present study we tested if chronic treatment with sildenafil, a phosphodiesterase 5 inhibitor that augments NO–cGMP signaling, can reduce the development of vasomotor dysfunction in Ercc1Δ/- mice. Ercc1Δ/- mice and wild-type littermates were treated with 10 mg/kg/d of sildenafil from the age of 6 to the age of 14 weeks. Blood pressure and in vivo and ex vivo vasomotor responses were measured at the end of the treatment period. Ercc1Δ/- mice developed decreased reactive hyperemia, and diminished NO–cGMP-dependent acetylcholine responses. The diminished acetylcholine response involved both endothelial and vascular smooth muscle cell signaling. Chronic sildenafil exclusively improved NO–cGMP signaling in VSMC, and had no effect on endothelium-derived hyperpolarization. Sildenafil also improved KCl hypocontractility in Ercc1Δ/- mice. All effects were blood pressure-independent. The findings might be of clinical importance for prevention of morbidities related to vascular aging as well as for progeria patients with a high risk of cardiovascular disease.
Wnt/β-Catenin Signaling in Oral Carcinogenesis

Oral carcinogenesis is a complex and multifactorial process that involves cumulative genetic and molecular alterations, leading to uncontrolled cell proliferation, impaired DNA repair and defective cell death. At the early stages, the onset of potentially malignant lesions in the oral mucosa, or oral dysplasia, is associated with higher rates of malignant progression towards carcinoma in situ and invasive carcinoma. Efforts have been made to get insights about signaling pathways that are deregulated in oral dysplasia, as these could be translated into novel markers and might represent promising therapeutic targets. In this context, recent evidence underscored the relevance of the Wnt/β-catenin signaling pathway in oral dysplasia, as this pathway is progressively “switched on” through the different grades of dysplasia (mild, moderate and severe dysplasia), with the consequent nuclear translocation of β-catenin and expression of target genes associated with the maintenance of representative traits of oral dysplasia, namely cell proliferation and viability. Intriguingly, recent studies provide an unanticipated connection between active β-catenin signaling and deregulated endosome trafficking in oral dysplasia, highlighting the relevance of endocytic components in oral carcinogenesis. This review summarizes evidence about the role of the Wnt/β-catenin signaling pathway and the underlying mechanisms that account for its aberrant activation in oral carcinogenesis.
A novel Turkish instrument for assessing quality of life in chronic otitis media –translation and validation of Zurich chronic middle ear inventory

Background/aim The Zurich Chronic Middle Ear Questionnaire (ZCMEI-21) is a newly-developed German-language questionnaire. The purpose of this study was to analyze the quality of life (QoL) of chronic otitis media (COM) patients and translate, transculturally adapt, and validate the ZCMEI-21 into Turkish. Materials and methods Based on internationally accepted guidelines, the ZCMEI-21 was translated into Turkish. To assess its validity, the total score of the ZCMEI-21-Tur was compared to the scores taken from the original validation study and a question that was directly related to the health-related QoL (HRQoL), as well as the general criterion EQ-5D-5L. Questionnaires were completed by healthy volunteers and the results were evaluated statistically. Results A total of 80 COM patients and 40 healthy volunteers were prospectively enrolled in this study. Regarding internal consistency, the questionnaire showed a Cronbach α of 0.94, which indicated high internal consistency. Moreover, internal consistency was also determined to be excellent for the Cronbach α of the individual subscales, as follows: ear sign symptoms, 0.79; hearing, 0.83; psychosocial impact, 0.91, and medical resources, 0.84. Conclusions The ZCMEI-21 was translated into Turkish and validated. Therefore, the ZCMEI-21-Tur was suitable for use in assessing HRQoL in adult patients with COM.
Characterizing #Backwoods on Instagram: “The Number One Selling All Natural Cigar”

We sought to assess the proportion of Backwoods (Imperial Tobacco Group Brands LLC) cigar-related posts to Instagram that may contain misleading claims, nature-evoking imagery, and appealing flavors. Inclusion criteria for this study included an Instagram post with the hashtag “#backwoods” from 30 August to 12 September 2018. Rules were established to content analyze (n = 1206) posts. Categories included misleading packaging (i.e., the post contained an image of a Backwoods product with the descriptor “natural” on the packaging), misleading promo (i.e., the corresponding caption to the post contained hashtag(s) like “#natural”, “#authentic”, “#alwaystrue”), nature-evoking imagery (i.e., the post contained images of grass, water, and pastural views along with a Backwoods product), flavors (i.e., the post contained a Backwoods product with brand-specific flavors on the packaging), flavor promo (i.e., the corresponding caption to the post contained hashtag(s) of Backwoods’ brand-specific flavors), marijuana-related (i.e., the post contained an image of marijuana next to a Backwoods pack, rolled cigars visibly contained marijuana, or hollowed-out cigars next to marijuana), smoking (the post contained an image of smoke or a lit cigar), brand-specific promo (i.e., the post contained an image of a Backwoods t-shirt, sweatshirt, hat, etc.), and perceived gender. Among the posts analyzed, 645 (53.5%) were marijuana-related, 564 (46.8%) were flavors, 463 (38.4%) were misleading packaging, 335 (27.8%) were flavor promo, 309 (25.6%) were misleading promo, 188 (15.6%) were nature-evoking imagery, 165 (13.7%) were smoking, 157 (13.0%) were brand-specific promo, and 239 (19.8%) were perceived male gender. Backwoods cigar-related posts to Instagram often contained misleading images and promotions of a “natural” tobacco product, images of marijuana use (in the form of blunt-making), brand-specific flavors, smoking, and promotional merchandise. Misleading images and the depictions of marijuana use in addition to the variety of flavor options may increase product appeal to consumers. These results underscore the need for comprehensive regulation of cigar products similar to cigarettes.
Horticultural Crop Production in High Tunnels in the United States: A Snapshot

High tunnels are becoming an increasingly important production tool for vegetable, small fruit, and cut flower growers in many parts of the United States. They provide a protected environment relative to the open field, allowing for earlier or later production of many crops, and they typically improve yield and quality as well as disease and pest management. Producers, ranging from small-scale market gardens to larger scale farms, are using high tunnels of various forms to produce for early markets, schedule production through extended seasons, grow specialty crops that require some environmental modification, and capture premium prices. The rapid ongoing adoption of high tunnels has resulted in numerous grower innovations and increased university research and extension programming to serve grower needs. An informal survey of extension specialists was conducted in 2007 to estimate numbers (area) of high tunnels and crops being grown in them by state, and to identify current research and extension efforts. Results of this survey provide an indication of the increasing importance of these structures for horticultural crop production across the country.
Silencing of long non-coding RNA Sox2ot inhibits oxidative stress and inflammation of vascular smooth muscle cells in abdominal aortic aneurysm via microRNA-145-mediated Egr1 inhibition

Long non-coding RNAs (lncRNAs) have been largely reported to contribute to the development and progression of abdominal aortic aneurysm (AAA), a common vascular degenerative disease. The present study was set out with the aim to investigate the possible role of lncRNA Sox2ot in the development of AAA. In this study, we found that lncRNA Sox2ot and early growth response factor-1 (Egr1) were highly expressed, while microRNA (miR)-145 was poorly expressed in Ang II-induced AAA mice and oxidative stress-provoked vascular smooth muscle cell (VSMC) model. Egr1 was a potential target gene of miR-145, and lncRNA Sox2ot could competitively bind to miR-145 to upregulate Egr1 expression. Overexpression of miR-145-5p was found to attenuate oxidative stress and inflammation by inhibiting Egr1 both in vivo and in vitro, which was counteracted by lncRNA Sox2ot. Taken together, the present study provides evidence that downregulation of lncRNA Sox2ot suppressed the expression of Egr1 through regulating miR-145, thus inhibiting the development of AAA, highlighting a theoretical basis for AAA treatment.
Unexpected Enhancement of HDACs Inhibition by MeS Substitution at C-2 Position of Fluoro Largazole

Given our previous finding that fluorination at the C18 position of largazole showed reasonably good tolerance towards inhibitory activity and selectivity of histone deacetylases (HDACs), further modification on the valine residue in the fluoro-largazole’s macrocyclic moiety with S-Me l-Cysteine or Glycine residue was performed. While the Glycine-modified fluoro analog showed poor activity, the S-Me l-Cysteine-modified analog emerged to be a very potent HDAC inhibitor. Unlike all previously reported C2-modified compounds in the largazole family (including our recent fluoro-largazole analogs) where replacement of the Val residue has failed to provide any potency improvement, the S-Me l-Cysteine-modified analog displayed significantly enhanced (five–nine-fold) inhibition of all the tested HDACs while maintaining the selectivity of HDAC1 over HDAC6, as compared to largazole thiol. A molecular modeling study provided rational explanation and structural evidence for the enhanced inhibitory activity. This new finding will aid the design of novel potent HDAC inhibitors.
Synergetic Effect of 2-Methacryloyloxyethyl Phosphorylcholine and Mesoporous Bioactive Glass Nanoparticles on Antibacterial and Anti-Demineralisation Properties in Orthodontic Bonding Agents

2-methacryloyloxyethyl phosphorylcholine (MPC) is known to have antibacterial and protein-repellent effects, whereas mesoporous bioactive glass nanoparticles (MBN) are known to have remineralisation effects. We evaluated the antibacterial and remineralisation effects of mixing MPC and MBN at various ratios with orthodontic bonding agents. MPC and MBN were mixed in the following weight percentages in CharmFil-Flow (CF): CF, 3% MPC, 5% MPC, 3% MPC + 3% MBN, and 3% MPC + 5% MBN. As the content of MPC and MBN increased, the mechanical properties of the resin decreased. At 5% MPC, the mechanical properties decreased significantly with respect to CF (shear bond strength), gelation of MPC occurred, and no significant difference was observed in terms of protein adsorption compared to the control group. Composition 3% MPC + 5% MBN exhibited the lowest protein adsorption because the proportion of hydrophobic resin composite decreased; CF (91.8 ± 4.8 μg/mL), 3% MPC (73.9 ± 2.6 μg/mL), 3% MPC + 3% MBN (69.4 ± 3.6 μg/mL), and 3% MPC + 5% MBN (55.9 ± 1.6 μg/mL). In experiments against S. mutans and E. coli, addition of MPC and MBN resulted in significant antibacterial effects. In another experiment, the anti-demineralisation effect was improved when MPC was added, and when MBN was additionally added, it resulted in a synergetic effect. When MPC and MBN were added at an appropriate ratio to the orthodontic bonding agents, the protein-repellent, antibacterial, and anti-demineralisation effects were improved. This combination could thus be an alternative way of treating white spot lesions.
Activation of Peroxisome Proliferator Nuclear Receptors Regulates Lipid Metabolism in the Placenta

Objective: Peroxisome proliferator activated receptors (PPARs), known regulators of lipid homeostasis in different tissues, are crucial during placental development. In this work, we aim to determine whether PPARs activation modulates lipid metabolism in the placenta from control and diabetic experimental models at midgestation. Materials and Methods: Placental explants obtained from control and neonatal-streptozotocin-induced- diabetic rats on day 13.5 of gestation were cultured in the presence or absence of ligands of the three PPARs isoforms (clofibrate, 15-deoxyδ 12,14 prostaglandin J2 and carbaprostacyclin; which are PPARα, PPARγ and PPARδ agonists respectively) for further analysis of lipid metabolism. Lipid levels (triglycerides, cholesterol, cholesteryl esters and phospholipids) were analysed by thin layer chromatography, de novo lipid synthesis was assessed by incorporation of 14C-acetate as a tracer, and lipid catabolism was studied through the evaluation of glycerol release. Results: Placental tissues from diabetic rats showed increased triglycerides and cholesteryl ester levels, decreased de novo lipid synthesis and enhanced lipid catabolism when compared to controls. PPAR α activation reduced lipid levels and synthesis, and increased lipid catabolism in the placenta. PPARγ activation did not modify placental lipid mass and catabolism, but significantly reduced de novo lipid synthesis. PPARδ ligands reduced phospholipid levels and de novo lipid synthesis, and increased placental lipid catabolism. Discussion: These results provide evidence of novel PPARs functions as regulators of placental lipid metabolism, a first step in the understanding of pathways that may allow the regulation of placental lipid metabolism and the prevention of the lipid overload transferred to the developing fetus in maternal diabetes.
Insecticidal effects of essential oils of eleven plant species from Lamiaceae on Sitophilus granarius (L.) (Coleoptera: Curculionidae)

Four different concentrations of the essential oils obtained from eleven plant species (Origanum onites L., Origanum rotundifolium Boiss., Rosmarinus officinalis L., Salvia hydrangea Dc., Salvia numerosa L., Salvia multicaulis Vahl., Salvia sclarea L., Satureja hortensis L., Satureja spicigera (C. Koch) Boiss. , Thymus fallax Fisch. & Mey. and Thymus sipyleus Boiss. (Lamiaceae) were tested against adults of Sitophilus granarius (L.) on Petri dishes. After exposure, mortality of the adults was determined at 24, 48 and 96 h. The results show that essential oils of O. onites, O. rotundifolium, R. officinalis, S. hydrangea, S. hortensis, S. spicigera, T. fallax and T. sipyleus have an insecticidal effect on adults of S. granarius in comparison with controls. The insecticidal effect was influenced by the doses of the essential oils and the exposure time. Higher doses and longer exposure time resulted in maximum toxicity on S. granarius. Treatment with essentials oils of O. onites, O. rotundifolium, R. officinalis, S. hydrangea, S. hortensis, S. spicigera, T. fallax and T. sipyleus leads to a higher and S. multicaulis to less mortality of adults of S. granarius but essential oils of S. numerosa and S. sclarea had no effect. The mortality rates after 96 h of treatment with the maximum dose (20 µl) of essential oils of S. hortensis, O. rotundifolium, O. onites, S. spicigera, R. officinalis, T. fallax T. sipyleus, S. hydrangea, S. multicaulis, S. sclarea and S. numerosa was determined as 100, 96.97, 95.27, 94.27, 93.93, 88.88, 82.82, 67.33, 55.21, 41.76 and 39.73 % for S. granarius, respectively. Separately, the mortality rates after 96 h of treatment with the 1 µl in dose of essential oils of S. hortensis was established to the highest mortality rate in S. granarius with 97.97 %, and 5, 10 and 20 µl in dose of S. hortensis with 100 %.
IMPACT OF LONG-TERM TILLAGE AND CROP ROTATION ON CONCENTRATION OF SOIL PARTICULATE ORGANIC MATTER ASSOCIATED CARBON AND NITROGEN

The soil management practices may pose intense effects on the nature and properties of soils. A field experiment was conducted during 2002 to 2007 on a Vanmeter farm of the Ohio State University South Centers at Piketon Ohio, USA to assess the long term influence of tillage practices and crop rotation on soil particulate organic matter allied with carbon and nitrogen. Tillage treatments including conventional (CT) and No-till (NT) were factored into continuous corn (CC), cornsoybean (CS) and corn – soybean-wheat-cowpea (CSW) rotations by following randomized complete block design with 6 replications. The results of long-term study showed that 12 percent of significant increase was observed in the particulate organic matter (POM) in NT by the passage of time. The particulate organic carbon (POC) concentration under NT increased (15 %) significantly when CT converted in to NT over five year. Furthermore, particulate organic nitrogen (PON) increased (12%) significantly under NT than under CT. Crop rotation had significant effects on POM and the effects were more prominent in the CSW rotation. The POM, POC concentration increased with time in CC (11%) and CSW (15%) rotations. As soil depth increases, significant decrease was observed in POM, POC and PON concentrations regardless of tillage and crop rotation treatments. Tillage and crop rotation had no significant influence on the physical parameters; however, with time as a factor in the interaction significantly influenced the physical properties. Changes in the physical properties of the soil by tillage practices and crop rotation are mainly due to soil disturbance, placement, amount and type of added biomass crop in the soil ecosystem. Physical properties of soil facilitate microbial activities, support chemical functions, improve protection C and improve the quality of soil.
Aspect qualitatif de l'activité protéolytique des lactobacilles thermophiles utilisés en fabrication de fromages à pâte pressée cuite

Qualitative aspect of proteolytic activity of thermophilic lactobacilli using in Swiss cheeses. The average peptidic pattern was established from 253 French Emmental cheeses sampled in 50 factories. It contained 53 peptidic peaks, 4 of which were the most important in quantity. Two Lactobacillus helveticus strains and five Lactobacillus delbrueckii ssp. lactis strains were tested in Emmental experimental cheesemaking in association with three different propionic strains (21 cheeses). The Propionibacterium freudenreichii strains did not affect the peptidic pattern of ripened Emmental cheese. On the other hand, 13 peptidic peaks were significantly influenced by the thermophilic lactobacilli strain. The two species of thermophilic lactobacilli were discriminated by three peptidic peaks. Seven peptidic peaks were correlated with the ammonia amount in ripened Emmental cheese. No significant correlation was found between peptidic peaks and SN/TN and NPN/TN. At the same time, the peptidic pattern produced by the seven lactobacilli strains were stud- ied in laboratory. The most specific peptidic peak of the French Emmental cheese were not found by using the Hammarsten casein as substrate. Another substrate, similar to hard cooked cheeses, lyophilized and sterilized by ionisation was tested. This substrate was obtained with microfiltered milk and Streptococcus thermophilusstrains only. This substrate digested by thermophilic lactobacilli allowed to find the specific peptidic peaks of the French Emmental cheese. For example, the 14th peak obtained in laboratory was significantly different according to lactobacilli species, as it was observed in the Emmental cheese experiments. This peak distinguished the strains inside the Lb. delbrueckii ssp. lactis too. peptidic pattern / proteolysis / thermophilic lactobacilli / Emmental
Fully Phased Sequence of a Diploid Human Genome Determined de Novo from the DNA of a Single Individual

In recent years, improved sequencing technology and computational tools have made de novo genome assembly more accessible. Many approaches, however, generate either an unphased or only partially resolved representation of a diploid genome, in which polymorphisms are detected but not assigned to one or the other of the homologous chromosomes. Yet chromosomal phase information is invaluable for the understanding of phenotypic trait inheritance in the cases of compound heterozygosity, allele-specific expression or cis-acting variants. Here we use a combination of tools and sequencing technologies to generate a de novo diploid assembly of the human primary cell line WI-38. First, data from PacBio single molecule sequencing and Bionano Genomics optical mapping were combined to generate an unphased assembly. Next, 10x Genomics linked reads were combined with the hybrid assembly to generate a partially phased assembly. Lastly, we developed and optimized methods to use short-read (Illumina) sequencing of flow cytometry-sorted metaphase chromosomes to provide phase information. The final genome assembly was almost fully (94%) phased with the addition of approximately 2.5-fold coverage of Illumina data from the sequenced metaphase chromosomes. The diploid nature of the final de novo genome assembly improved the resolution of structural variants between the WI-38 genome and the human reference genome. The phased WI-38 sequence data are available for browsing and download at wi38.research. calicolabs.com. Our work shows that assembling a completely phased diploid genome de novo from the DNA of a single individual is now readily achievable.
Twice-daily vs higher-dose once-daily thoracic radiotherapy for limited-disease small-cell lung cancer

Abstract Introduction: The optimal dose and fractionation of thoracic radiotherapy (RT) for limited-disease small-cell lung cancer (LD-SCLC) remain controversial. This meta-analysis was performed to compare the efficacy and RT toxicity between twice-daily thoracic RT (45 Gy with 1.5 Gy twice daily) and higher-dose once-daily RT (60–72 Gy with 1.8 Gy/2 Gy once daily) administered with chemotherapy in LD-SCLC patients. Methods: PubMed, EMBASE, Web of Science, and the Cochrane Library were searched up to March 19, 2020 for studies that compared twice-daily thoracic RT (45 Gy with 1.5 Gy twice daily over 3 weeks) with higher-dose once-daily RT (60–72 Gy with 1.8 Gy/2 Gy once daily over 6–8 weeks) in LD-SCLC patients. Results: Five studies involving 13,726 patients were included in this analysis. Compared with the once-daily thoracic RT group, the 1-year overall survival (OS) rate (P < .001), the 2-year OS rate (P < .001), the 5-year OS rate (P < .001), the mOS (P < .001), and the 1-year LRFS rate (P = .048) were significantly improved in the twice-daily RT group. The toxic effects of RT (esophagitis: P = .293; pneumonitis: P = .103) were similar in both groups. Conclusion: Compared with the higher-dose once-daily regimen, the twice-daily thoracic radiotherapy regimen improved efficacy but did not increase RT toxicity in LD-SCLC patients.