Search results for: differentially expressed genes

Authors: R. Di Lorenzo, S. Laneri, A. Sacchi

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Hair surface properties affect hair texture and shine, whereas the healthy state of the hair cortex sways hair ends. Even if cosmetic treatments are intrinsically safe, there is potentially damaging action on the hair fibers. Loss of luster, frizz, split ends, and other hair problems are particularly prevalent among people who repeatedly alter the natural style of their hair or among people with intrinsically weak hair. Technological and scientific innovations in hair care thus become invaluable allies to preserve their natural well-being and shine. The study evaluated restoring keratin-like ingredients that improve hair fibers' structural integrity, increase tensile strength, improve hair manageability and moisturizing. The hair shaft is composed of 65 - 95% of keratin. It gives the hair resistance, elasticity, and plastic properties and also contributes to their waterproofing. Providing exogenous keratin is, therefore, a practical approach to protect and nourish the hair. By analyzing the amino acid composition of keratin, we find a high frequency of hydrophobic amino acids. It confirms the critical role interactions, mainly hydrophobic, between cosmetic products and hair. The active ingredient analyzed comes from vegetable proteins through an enzymatic cut process that selected only oligo- and polypeptides (> 3500 KDa) rich in amino acids with hydrocarbon side chains apolar or sulfur. These chemical components are the most expressed amino acids at the level of the capillary keratin structure, and it determines the most significant possible compatibility with the target substrate. Given the biological variability of the sources, it isn't easy to define a constant and reproducible molecular formula of the product. Still, it consists of hydroxypropiltrimonium vegetable peptides with keratin-like performances. 20 natural hair tresses (30 cm in length and 0.50 g weight) were treated with the investigated products (5 % v/v aqueous solution) following a specific protocol and compared with non-treated (Control) and benchmark-keratin-treated strands (Benchmark). Their brightness, moisture content, cortical and surface integrity, and tensile strength were evaluated and statistically compared. Keratin-like treated hair tresses showed better results than the other two groups (Control and Benchmark). The product improves the surface with significant regularization of the cuticle closure, improves the cortex and the peri-medullar area filling, gives a highly organized and tidy structure, delivers a significant amount of sulfur on the hair, and is more efficient moisturization and imbibition power, increases hair brightness. The hydroxypropyltrimonium quaternized group added to the C-terminal end interacts with the negative charges that form on the hair after washing when disheveled and tangled. The interactions anchor the product to the hair surface, keeping the cuticles adhered to the shaft. The small size allows the peptides to penetrate and give body to the hair, together with a conditioning effect that gives an image of healthy hair. Results suggest that the product is a valid ally in numerous restructuring/conditioning, shaft protection, straightener/dryer-damage prevention hair care product.

Keywords: conditioning, hair damage, hair, keratin, polarized light microscopy, scanning electron microscope, thermogravimetric analysis

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Authors: E. Locatelli, I. Monaco, R. C. Martin, Y. Li, R. Pini, M. Chiariello, M. Comes Franchini

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Despite the many advantages of application of nanomaterials in the field of nanomedicine, increasing concerns have been expressed on their potential adverse effects on human health. There is urgency for novel green strategies toward novel materials with enhanced biocompatibility using safe reagents. Photothermal ablation therapy, which exploits localized heat increase of a few degrees to kill cancer cells, has appeared recently as a non-invasive and highly efficient therapy against various cancer types; anyway new agents able to generate hyperthermia when irradiated are needed and must have precise biocompatibility in order to avoid damage to healthy tissues and prevent toxicity. Recently, there has been increasing interest in magnesium as a biomaterial: it is the fourth most abundant cation in the human body, and it is essential for human metabolism. However magnesium nanoparticles (Mg NPs) have had limited diffusion due to the high reduction potential of magnesium cations, which makes NPs synthesis challenging. Herein, we report the synthesis of Mg NPs and their surface functionalization for the obtainment of a stable and biocompatible nanomaterial suitable for photothermal ablation therapy against cancer. We synthesized the Mg crystals by reducing MgCl2 with metallic lithium and exploiting naphthalene as an electron carrier: the lithium–naphthalene complex acts as the real reducing agent. Firstly, the nanocrystal particles were coated with the ligand 12-ethoxy ester dodecanehydroxamic acid, and then entrapped into water-dispersible polymeric micelles (PMs) made of the FDA-approved PLGA-b-PEG-COOH copolymer using the oil-in-water emulsion technique. Lately, we developed a more straightforward methodology by introducing chitosan, a highly biocompatible natural product, at the beginning of the process, simultaneously using lithium–naphthalene complex, thus having a one-pot procedure for the formation and surface modification of MgNPs. The obtained MgNPs were purified and fully characterized, showing diameters in the range of 50-300 nm. Notably, when coated with chitosan the particles remained stable as dry powder for more than 10 months. We proved the possibility of generating a temperature rise of a few to several degrees once MgNPs were illuminated using a 810 nm diode laser operating in continuous wave mode: the temperature rise resulted significant (0-15 °C) and concentration dependent. We then investigated potential cytotoxicity of the MgNPs: we used HN13 epithelial cells, derived from a head and neck squamous cell carcinoma and the hepa1-6 cell line, derived from hepatocellular carcinoma and very low toxicity was observed for both nanosystems. Finally, in vivo photothermal therapy was performed on xenograft hepa1-6 tumor bearing mice: the animals were treated with MgNPs coated with chitosan and showed no sign of suffering after the injection. After 12 hours the tumor was exposed to near-infrared laser light. The results clearly showed an extensive damage to tumor tissue after only 2 minutes of laser irradiation at 3Wcm-1, while no damage was reported when the tumor was treated with the laser and saline alone in control group. Despite the lower photothermal efficiency of Mg with respect to Au NPs, we consider MgNPs a promising, safe and green candidate for future clinical translations.

Keywords: chitosan, magnesium nanoparticles, nanomedicine, photothermal therapy

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Authors: Mario Tauzene Afonso Matangue, Ivan Andres Sanchez Ortiz

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The Metropolitan area of Maputo (Mozambique Capital City) is located in semi-arid zone (800 mm annual rainfall) with 1101170 million inhabitants. On the west side, there are the flatlands of Infulene where the Mulauze River flows towards to the Indian Ocean, receiving at this site, the storm water contaminated with sanitary sewage from Maputo, transported through a concrete open channel. In Infulene, local communities grow salads crops such as tomato, onion, garlic, lettuce, and cabbage, which are then commercialized and consumed in several markets in Maputo City. Lettuce is the most daily consumed salad crop in different meals, generally in fast-foods, breakfasts, lunches, and dinners. However, the risk of infection by several pathogens due to the consumption of lettuce, using the Quantitative Microbial Risk Assessment (QMRA) tools, is still unknown since there are few studies or publications concerning to this matter in Mozambique. This work is aimed at determining the annual risk arising from the consumption of lettuce grown in Infulene valley, in Maputo, using QMRA tools. The exposure model was constructed upon the volume of contaminated water remaining in the lettuce leaves, the empirical relations between the number of pathogens and the indicator of microorganisms (E. coli), the consumption of lettuce (g) and reduction of pathogens (days). The reference pathogens were Vibrio cholerae, Cryptosporidium, norovirus, and Ascaris. The water quality samples (E. coli) were collected in the storm water channel from January 2016 to December 2018, comprising 65 samples, and the urban lettuce consumption data were collected through inquiry in Maputo Metropolis covering 350 persons. A non-parametric bootstrap was performed involving 10,000 iterations over the collected dataset, namely, water quality (E. coli) and lettuce consumption. The dose-response models were: Exponential for Cryptosporidium, Kummer Confluent hypergeomtric function (1F1) for Vibrio and Ascaris Gaussian hypergeometric function (2F1-(a,b;c;z) for norovirus. The annual infection risk estimates were performed using R 3.6.0 (CoreTeam) software by Monte Carlo (Latin hypercubes), a sampling technique involving 10,000 iterations. The annual infection risks values expressed by Median and the 95th percentile, per person per year (pppy) arising from the consumption of lettuce are as follows: Vibrio cholerae (1.00, 1.00), Cryptosporidium (3.91x10⁻³, 9.72x 10⁻³), nororvirus (5.22x10⁻¹, 9.99x10⁻¹) and Ascaris (2.59x10⁻¹, 9.65x10⁻¹). Thus, the consumption of the lettuce would result in greater risks than the tolerable levels ( < 10⁻³ pppy or 10⁻⁶ DALY) for all pathogens, and the Vibrio cholerae is the most virulent pathogens, according to the hit-single models followed by the Ascaris lumbricoides and norovirus. The sensitivity analysis carried out in this work pointed out that in the whole QMRA, the most important input variable was the reduction of pathogens (Spearman rank value was 0.69) between harvest and consumption followed by water quality (Spearman rank value was 0.69). The decision-makers (Mozambique Government) must strengthen the prevention measures related to pathogens reduction in lettuce (i.e., washing) and engage in wastewater treatment engineering.

Keywords: annual infections risk, lettuce, non-parametric bootstrapping, quantitative microbial risk assessment tools

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Authors: Thanthrige Thiunuwan Priyathilaka, Don Anushka Sandaruwan Elvitigala, Bong-Soo Lim, Hyung-Bok Jeong, Jehee Lee

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Toll like receptors (TLRs) are a phylogeneticaly conserved family of pattern recognition receptors, which participates in the host immune responses against various pathogens and pathogen derived mitogen. TLR21, a non-mammalian type, is almost restricted to the fish species even though those can be identified rarely in avians and amphibians. Herein, this study was carried out to identify and characterize TLR21 from rock bream (Oplegnathus fasciatus) designated as RbTLR21, at transcriptional and genomic level. In this study, the full length cDNA and genomic sequence of RbTLR21 was identified using previously constructed cDNA sequence database and BAC library, respectively. Identified RbTLR21 sequence was characterized using several bioinformatics tools. The quantitative real time PCR (qPCR) experiment was conducted to determine tissue specific expressional distribution of RbTLR21. Further, transcriptional modulation of RbTLR21 upon the stimulation with Streptococcus iniae (S. iniae), rock bream iridovirus (RBIV) and Edwardsiella tarda (E. tarda) was analyzed in spleen tissues. The complete coding sequence of RbTLR21 was 2919 bp in length which can encode a protein consisting of 973 amino acid residues with molecular mass of 112 kDa and theoretical isoelectric point of 8.6. The anticipated protein sequence resembled a typical TLR domain architecture including C-terminal ectodomain with 16 leucine rich repeats, a transmembrane domain, cytoplasmic TIR domain and signal peptide with 23 amino acid residues. Moreover, protein folding pattern prediction of RbTLR21 exhibited well-structured and folded ectodomain, transmembrane domain and cytoplasmc TIR domain. According to the pair wise sequence analysis data, RbTLR21 showed closest homology with orange-spotted grouper (Epinephelus coioides) TLR21with 76.9% amino acid identity. Furthermore, our phylogenetic analysis revealed that RbTLR21 shows a close evolutionary relationship with its ortholog from Danio rerio. Genomic structure of RbTLR21 consisted of single exon similar to its ortholog of zebra fish. Sevaral putative transcription factor binding sites were also identified in 5ʹ flanking region of RbTLR21. The RBTLR 21 was ubiquitously expressed in all the tissues we tested. Relatively, high expression levels were found in spleen, liver and blood tissues. Upon induction with rock bream iridovirus, RbTLR21 expression was upregulated at the early phase of post induction period even though RbTLR21 expression level was fluctuated at the latter phase of post induction period. Post Edwardsiella tarda injection, RbTLR transcripts were upregulated throughout the experiment. Similarly, Streptococcus iniae induction exhibited significant upregulations of RbTLR21 mRNA expression in the spleen tissues. Collectively, our findings suggest that RbTLR21 is indeed a homolog of TLR21 family members and RbTLR21 may be involved in host immune responses against bacterial and DNA viral infections.

Keywords: rock bream, toll like receptor 21 (TLR21), pattern recognition receptor, genomic characterization

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Authors: D. Muyama, M. Luyiga, P. Buyungo, D. Chemonges, M. Namukwaya, L. Ssekabembe, B. Lukwago, D. Kyamagwa

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Context: The study focuses on the sustainability of health interventions in Uganda, particularly in the private sector, beyond donor-funded project periods. The Population Services International (PSI) implemented the Women Health Project (WHP) to ensure continued access to quality family planning, cervical cancer screening, and post-abortion care services through private clinics. Research Aim: The aim of the study is to assess the continued access to quality family planning, cervical cancer screening, and post-abortion care services through the private sector after the closure or reduction in funding of the WHP. Methodology: PSI trained and mentored 83 clinics to establish functional systems in self-regulatory quality improvement, supply chain, referral, and demand creation. The clinics were also connected to the national reporting system and utilized Ministry of Health reporting tools. An assessment tool with six criteria was designed and used to evaluate the progress of the clinics. Clinics scoring 75% and above were considered independent and graduated from the program. Findings: Out of the 83 private clinics, 56 successfully met the graduation criteria and graduated from the program, while 25 lost interest and were gradually dropped. Two clinics failed to achieve the criteria due to leadership challenges. The 59 graduating clinics continued to provide high-quality family planning services, including IUD, implant, Depo-Provera, oral contraceptives, and post-abortion care. All graduating clinics were reassessed and found to still be capable of offering services, attributing their success to government stock availability and acquired skills through mentorships. The clinics expressed appreciation to PSI for the sustainable plan that allowed them to operate beyond the project period. Theoretical Importance: This study contributes to the understanding of sustainability planning and the importance of clinic owners' attitudes and buy-in for continued service provision. It emphasizes the implementation of sustainability plans through existing structures to leverage available resources and ensure continuity of care. Data Collection and Analysis Procedures: The study collected data through the assessment tool that evaluated the progress of clinics based on the established criteria. The tool was scored out of 100%, and clinics scoring above 75% were deemed independent. The findings were analyzed quantitatively to determine the success rate of clinics in meeting the graduation criteria. Questions Addressed: The study addresses the question of whether private clinics in Uganda can sustain the provision of family planning, cervical cancer screening, and post-abortion care services after the closure or reduction in funding of the WHP. Conclusion: The study concludes that the attitude and buy-in of clinic owners are essential for sustainability planning. Implementing sustainability plans through existing structures and leveraging available resources are crucial for the continuity of care after the end of a project or reduced funding. The findings highlight the importance of establishing sustainable plans to ensure continued access to essential health services beyond the project period. Contributions: This study contributes to the existing knowledge for programmers implementing or intending to implement donor-funded projects. It provides insights into designing sustainable plans that enable the independent operation of clinics even after the end of a project.

Keywords: graduation, family planning, systems strengthening, sustainability

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Authors: Chung-Ming Lo, Chung-Chien Lee

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In many countries, the lifetime prevalence of shoulder pain is up to 70%. In America, the health care system spends 7 billion per year about the healthy issues of shoulder pain. With respect to the origin, up to 70% of shoulder pain is attributed to rotator cuff lesions This study proposed a computer-aided diagnosis (CAD) system to assist radiologists classifying rotator cuff lesions with less operator dependence. Quantitative features were extracted from the shoulder ultrasound images acquired using an ALOKA alpha-6 US scanner (Hitachi-Aloka Medical, Tokyo, Japan) with linear array probe (scan width: 36mm) ranging from 5 to 13 MHz. During examination, the postures of the examined patients are standard sitting position and are followed by the regular routine. After acquisition, the shoulder US images were drawn out from the scanner and stored as 8-bit images with pixel value ranging from 0 to 255. Upon the sonographic appearance, the boundary of each lesion was delineated by a physician to indicate the specific pattern for analysis. The three lesion categories for classification were composed of 20 cases of tendon inflammation, 18 cases of calcific tendonitis, and 18 cases of supraspinatus tear. For each lesion, second-order statistics were quantified in the feature extraction. The second-order statistics were the texture features describing the correlations between adjacent pixels in a lesion. Because echogenicity patterns were expressed via grey-scale. The grey-scale co-occurrence matrixes with four angles of adjacent pixels were used. The texture metrics included the mean and standard deviation of energy, entropy, correlation, inverse different moment, inertia, cluster shade, cluster prominence, and Haralick correlation. Then, the quantitative features were combined in a multinomial logistic regression classifier to generate a prediction model of rotator cuff lesions. Multinomial logistic regression classifier is widely used in the classification of more than two categories such as the three lesion types used in this study. In the classifier, backward elimination was used to select a feature subset which is the most relevant. They were selected from the trained classifier with the lowest error rate. Leave-one-out cross-validation was used to evaluate the performance of the classifier. Each case was left out of the total cases and used to test the trained result by the remaining cases. According to the physician’s assessment, the performance of the proposed CAD system was shown by the accuracy. As a result, the proposed system achieved an accuracy of 86%. A CAD system based on the statistical texture features to interpret echogenicity values in shoulder musculoskeletal ultrasound was established to generate a prediction model for rotator cuff lesions. Clinically, it is difficult to distinguish some kinds of rotator cuff lesions, especially partial-thickness tear of rotator cuff. The shoulder orthopaedic surgeon and musculoskeletal radiologist reported greater diagnostic test accuracy than general radiologist or ultrasonographers based on the available literature. Consequently, the proposed CAD system which was developed according to the experiment of the shoulder orthopaedic surgeon can provide reliable suggestions to general radiologists or ultrasonographers. More quantitative features related to the specific patterns of different lesion types would be investigated in the further study to improve the prediction.

Keywords: shoulder ultrasound, rotator cuff lesions, texture, computer-aided diagnosis

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Authors: Dadash Huseynov, Elmira Aliyeva, Robert Hoogendoorn, Salomon Kroonenberg

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The study of organic material in bottom sediments together with lithologic and biostratigraphic data improves our understanding of the evolution of fluvial and deltaic systems. The modern Kura River delta is located in the Southwest Caspian Sea and is fluvial-dominated. The river distributes its sediment load through three channels oriented North-East, South-East, and South-West. The offshore modern delta consists of thinly bedded or laminated silty clays and dark grey clays. Locally sand and shell-rich horizons occur. Onshore delta is composed of channel-levee sands and floodplain silts and clays. Overall sedimentation rates in the delta determined by the 210Pb method range between 1.5-3.0 cm/yr. We investigated the distribution of organic material in the deltaic sediments in 300 samples selected from 3m deep piston cores. The studies of transparent sections demonstrate that deltaic sediments are enriched in terrestrial debris. It is non-transparent and has an irregular, isometric, or elongated shape, angular edges, black or dark-brown colour, and a clearly expressed fabric. Partially it is dissolved at the edges and is replaced by iron sulphides. Fragments of marine algae have more smooth edges, brown colour. They are transparent; the fabric is rarely preserved. The evidences of dissolution and gelification are well observed. Iron sulphides are common. The recorded third type of organic material has a round, drop-like, or oval shape and belongs to planktonic organisms. Their initial organic material is strongly transformed or replaced by dark organic compounds, probably, neoplasms. The particles are red-brown and transparent. The iron sulphides are not observed. The amount of Corg in the uppermost portion of sediments accumulated in the offshore Kura River delta varies from 0.2 to 1.22%, with median values of 0.6-0.8%. In poorly sorted sediments Corg content changes from 0.24 to 0.97% (average 0.69%), silty-sandy clay - 0.45 to 1.22% (average 0.77%), sandy-silty clay - 0.5 to 0.97% (average 0.67%), silty clay - 0.52 to 0.95% (average 0.70%). The data demonstrate that in sediments deposited during Caspian Sea high stand in 1929, the minimum of Corg content is localised near the mouth of the main south-eastern distributary channel and coincides with the minimum of the clay fraction. At the same time, the maximum of organic matter content locates near the mouth of the eastern channel, which was inactive at that time. In sediments accumulated during the last Caspian Sea low stand in 1977, the area of Corg minimum is attached to the north-eastern distributary’s mouth. It indicates the high activity of this distributary during the Caspian Sea fall. The area of Corg minimum is also recorded around the mouth of the main channel and eastern part of the delta. Maximums of Corg and clay fraction shift towards the basin. During the Caspian high stand in 1995, the minimum of Corg content is again observed in the mouth of the main south-eastern channel. The distribution of organic matter in the modern sediments of the Kura river delta displays the strong time dependence and reflects progradational-retrogradational cycles of evolution of this fluvial-deltaic system.

Keywords: high and low stands, Kura River delta, South Caspian Sea, organic matter

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Authors: Ekta Yadav, Sukanta Bhattacharya, Brijesh Yadav, Ariel Hus, Jagjit Yadav

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Background and Significance: Respiratory exposure to toxicants (chemicals or particulates) causes disruption of lung homeostasis leading to lung toxicity/injury manifested as pulmonary inflammation, edema, and/or other effects depending on the type and extent of exposure. This emphasizes the need for investigating toxicant type-specific mechanisms to understand therapeutic targets. Aquaporins, aka water channels, are known to play a role in lung homeostasis. Particularly, the two major lung aquaporins AQP5 and AQP1 expressed in alveolar epithelial and vasculature endothelia respectively allow for movement of the fluid between the alveolar air space and the associated vasculature. In view of this, the current study is focused on understanding the regulation of lung aquaporins and other targets during inhalation exposure to toxic chemicals (Cigarette smoke chemicals) versus toxic particles (Carbon nanoparticles) or co-exposures to understand their relevance as markers of injury and intervention. Methodologies: C57BL/6 mice (5-7 weeks old) were used in this study following an approved protocol by the University of Cincinnati Institutional Animal Care and Use Committee (IACUC). The mice were exposed via oropharyngeal aspiration to multiwall carbon nanotube (MWCNT) particles suspension once (33 ugs/mouse) followed by housing for four weeks or to Cigarette smoke Extract (CSE) using a daily dose of 30µl/mouse for four weeks, or to co-exposure using the combined regime. Control groups received vehicles following the same dosing schedule. Lung toxicity/injury was assessed in terms of homeostasis changes in the lung tissue and lumen. Exposed lungs were analyzed for transcriptional expression of specific targets (AQPs, surfactant protein A, Mucin 5b) in relation to tissue homeostasis. Total RNA from lungs extracted using TRIreagent kit was analyzed using qRT-PCR based on gene-specific primers. Total protein in bronchoalveolar lavage (BAL) fluid was determined by the DC protein estimation kit (BioRad). GraphPad Prism 5.0 (La Jolla, CA, USA) was used for all analyses. Major findings: CNT exposure alone or as co-exposure with CSE increased the total protein content in the BAL fluid (lung lumen rinse), implying compromised membrane integrity and cellular infiltration in the lung alveoli. In contrast, CSE showed no significant effect. AQP1, required for water transport across membranes of endothelial cells in lungs, was significantly upregulated in CNT exposure but downregulated in CSE exposure and showed an intermediate level of expression for the co-exposure group. Both CNT and CSE exposures had significant downregulating effects on Muc5b, and SP-A expression and the co-exposure showed either no significant effect (Muc5b) or significant downregulating effect (SP-A), suggesting an increased propensity for infection in the exposed lungs. Conclusions: The current study based on the lung toxicity mouse model showed that both toxicant types, particles (CNT) versus chemicals (CSE), cause similar downregulation of lung innate defense targets (SP-A, Muc5b) and mostly a summative effect when presented as co-exposure. However, the two toxicant types show differential induction of aquaporin-1 coinciding with the corresponding differential damage to alveolar integrity (vascular permeability). Interestingly, this implies the potential of AQP1 as a differential marker of toxicant type-specific lung injury.

Keywords: aquaporin, gene expression, lung injury, toxicant exposure

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Authors: Amberly Brigden, Ali Heawood, Emma C. Anderson, Richard Morris, Esther Crawley

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Background: Paediatric chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) is characterised by persistent, disabling fatigue. Health services see patients below the age of 12. This age group experience high levels of disability, with low levels of school attendance, high levels of fatigue, anxiety, functional disability and pain. CFS/ME interventions have been developed for adolescents, but the developmental needs of younger children suggest treatment should be tailored to this age group. Little is known about how intervention should be delivered to this age group, and further work is needed to explore this. Qualitative research aids patient-centered design of health intervention. Methods: Five to 11-year-olds and their parents were recruited from a specialist CFS/ME service. Semi-structured interviews explored the families’ experience of the condition and perspectives on treatment. Interactive and arts-based methods were used. Interviews were audio-recorded, transcribed and analysed thematically. Qualitative Results: 14 parents and 7 children were interviewed. Early analysis of the interviews revealed the importance of the social-ecological setting of the child, which led to themes being developed in the context of Systems Theory. Theme one relates to the level of the child, theme two the family system, theme three the organisational and societal systems, and theme four cuts-across all levels. Theme1: The child’s capacity to describe, understand and manage their condition. Younger children struggled to describe their internal experiences, such as physical symptoms. Parents felt younger children did not understand some concepts of CFS/ME and did not have the capabilities to monitor and self-regulate their behaviour, as required by treatment. A spectrum of abilities was described; older children (10-11-year-olds) were more involved in clinical sessions and had more responsibility for self-management. Theme2: Parents’ responsibility for managing their child’s condition. Parents took responsibility for regulating their child’s behaviour in accordance with the treatment programme. They structured their child’s environment, gave direct instructions to their child, and communicated the needs of their child to others involved in care. Parents wanted their child to experience a 'normal' childhood and took steps to shield their child from medicalization, including diagnostic labels and clinical discussions. Theme3: Parental isolation and the role of organisational and societal systems. Parents felt unsupported in their role of managing the condition and felt negative responses from primary care health services and schools were underpinned by a lack of awareness and knowledge about CFS/ME in younger children. This sometimes led to a protracted time to diagnosis. Parents felt that schools have the potential important role in managing the child’s condition. Theme4: Complexity and uncertainty. Many parents valued specialist treatment (which included activity management, physiotherapy, sleep management, dietary advice, medical management and psychological support), but felt it needed to account for the complexity of the condition in younger children. Some parents expressed uncertainty about the diagnosis and the treatment programme. Conclusions: Interventions for younger children need to consider the 'systems' (family, organisational and societal) involved in the child’s care. Future research will include interviews with clinicians and schools supporting younger children with CFS/ME.

Keywords: chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME), pediatric, qualitative, treatment

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Authors: Rajeswari Raguraman, Sowmya Parameswaran, Krishnakumar Subramanian, Jagat Kanwar, Rupinder Kanwar

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Background: Tumor microenvironment has been implicated in several cancers to regulate cell growth, invasion and metastasis culminating in outcome of therapy. Tumor stroma consists of multiple cell types that are in constant cross-talk with the tumor cells to favour a pro-tumorigenic environment. Not much is known about the existence of tumor microenvironment in the pediatric intraocular malignancy, Retinoblastoma (RB). In the present study, we aim to understand the multiple stromal cellular subtypes and tumor stromal interactions expressed in RB tumors. Materials and Methods: Immunohistochemistry for stromal cell markers CD31, CD68, alpha-smooth muscle (α-SMA), vimentin and glial fibrillary acidic protein (GFAP) was performed on formalin fixed paraffin embedded tissues sections of RB (n=12). The differential expression of stromal target molecules; fibroblast activation protein (FAP), tenascin-C (TNC), osteopontin (SPP1), bone marrow stromal antigen 2 (BST2), stromal derived factor 2 and 4 (SDF2 and SDF4) in primary RB tumors (n=20) and normal retina (n=5) was studied by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blotting. The differential expression was correlated with the histopathological features of RB. The interaction between RB cell lines (Weri-Rb-1, NCC-RbC-51) and Bone marrow stromal cells (BMSC) was also studied using direct co-culture and indirect co-culture methods. The functional effect of the co-culture methods on the RB cells was evaluated by invasion and proliferation assays. Global gene expression was studied by using Affymetrix 3’ IVT microarray. Pathway prediction was performed using KEGG and the key molecules were validated using qRT-PCR. Results: The immunohistochemistry revealed the presence of several stromal cell types such as endothelial cells (CD31+;Vim+/-); macrophages (CD68+;Vim+/-); Fibroblasts (Vim+; CD31-;CD68- );myofibroblasts (α-SMA+/ Vim+) and invading retinal astrocytes/ differentiated retinal glia (GFAP+; Vim+). A characteristic distribution of these stromal cell types was observed in the tumor microenvironment, with endothelial cells predominantly seen in blood vessels and macrophages near actively proliferating tumor or necrotic areas. Retinal astrocytes and glia were predominant near the optic nerve regions in invasive tumors with sparse distribution in tumor foci. Fibroblasts were widely distributed with rare evidence of myofibroblasts in the tumor. Both gene and protein expression revealed statistically significant (P<0.05) up-regulation of FAP, TNC and BST2 in primary RB tumors compared to the normal retina. Co-culture of BMSC with RB cells promoted invasion and proliferation of RB cells in direct and indirect contact methods respectively. Direct co-culture of RB cell lines with BMSC resulted in gene expression changes in ECM-receptor interaction, focal adhesion, IL-8 and TGF-β signaling pathways associated with cancer. In contrast, various metabolic pathways such a glucose, fructose and amino acid metabolism were significantly altered under the indirect co-culture condition. Conclusion: The study suggests that the close interaction between RB cells and the stroma might be involved in RB tumor invasion and progression which is likely to be mediated by ECM-receptor interactions and secretory factors. Targeting the tumor stroma would be an attractive option for redesigning treatment strategies for RB.

Keywords: gene expression profiles, retinoblastoma, stromal cells, tumor microenvironment

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Authors: Kristina Karapetyan, Flora Tkhruni, Tsovinar Balabekyan, Arevik Israyelyan, Tatyana Khachatryan

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The ability of the lactic acid bacteria (LAB) to prevent and cure a variety of diseases, their protective role against infections and colonization of pathogenic microorganisms in the digestive tract, has lead to the coining of the term probiotics or pro-life. LAB inhibiting the growth of pathogenic and food spoilage microorganisms, maintaining the nutritive quality and improving the shelf life of foods. They have also been used as flavor and texture producers. Enterococcus strains have been used for treatment of diseases such as diarrhea or antibiotic associated diarrhea, inflammatory pathologies that affect colon such as irritable bowel syndrome, or immune regulation, diarrhea caused by antibiotic treatments. The obtaining and investigation of biological properties of proteinoceous antibiotics, on the basis of probiotic LAB shown, that bacteriocins, metabiotics, and peptides of LAB represent bactericides have a broad range of activity and are excellent candidates for development of new prophylactic and therapeutic substances to complement or replace conventional antibiotics. The genotyping by 16S rRNA sequencing for LAB were used. Cell free culture broth (CFC) broth was purified by the Gel filtration method on the Sephadex Superfine G 25 resin. Antimicrobial activity was determined by spot-on-lawn method and expressed in arbitrary units (AU/ml). The diversity of multidrug-resistance (MDR) of pathogenic strains to antibiotics, most widely used for treatment of human diseases in the Republics of Armenia and Nagorno Karabakh were examined. It was shown, that difference of resistance of pathogens to antibiotics depends on their isolation sources. The influences of partially purified antimicrobial preparations (AMP), obtained from the different strains of Enterococcus genus on the growth of MDR pathogenic bacteria were investigated. It was shown, that bacteriocin containing partially purified preparations, obtained from different strains of Enterococcus faecium and durans species, possess bactericidal or bacteriostatic activity against antibiotic resistant intestinal, spoilage and food-borne pathogens such as Listeria monocytogenes, Staphylococcus aureus, E. coli, and Salmonella. Endemic strains of LAB, isolated from Matsoni made from donkey, buffalo and goat milk, shown broad spectrum of activity against food spoiling microorganisms, moulds and fungi, such as Salmonella sp., Esherichia coli, Aspergillus and Penicillium species. Highest activity against MDR pathogens shown bacteria, isolated from goat milk products. High stability of the investigated strains of the genus Enerococcus, isolated from samples of matsun from different regions of Nagorno-Karabakh (NKR) to the antibiotics was shown. The obtained data show high stability of the investigated different strains of the genus Enerococcus. The high genetic diversity in Enterococcus group suggests adaptations for specific mutations in different environments. Thus, endemic strains of LAB are able to produce bacteriocins with high and different inhibitory activity against broad spectrum of microorganisms isolated from different sources and belong to different taxonomic group. Prospect of the use of certain antimicrobial preparations against pathogenic strains is obvious. These AMP can be applied for long term use against different etiology antibiotic resistant pathogens for prevention or treatment of infectional diseases as an alternative to antibiotics.

Keywords: antimicrobial biopreparation, endemic lactic acid bacteria, intra-species diversity, multidrug resistance of pathogens

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Authors: K. Karapetyan, F. Tkhruni, A. Aghajanyan, T. S. Balabekyan, L. Arstamyan

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Introduction: Globalization of the food supply has created the conditions favorable for the emergence and spread of food-borne and especially dangerous pathogens (EDP) in developing countries. The fresh-cut fruit and vegetable industry is searching for alternatives to replace chemical treatments with biopreservative approaches that ensure the safety of the processed foods product. Antimicrobial compounds of lactic acid bacteria (LAB) possess bactericidal or bacteriostatic activity against intestinal pathogens, spoilage organisms and food-borne pathogens such as Listeria monocytogenes, Staphylococcus aureus and Salmonella. Endemic strains of LAB were isolated. The strains, showing broad spectrum of antimicrobial activity against food spoiling microorganisms, were selected. The genotyping by 16S rRNA sequencing, GS-PCR, RAPD PCR methods showed that they were presented by Lactobacillus rhamnosus109, L.plantarum 65, L.plantarum 66 and Enterococcus faecium 64 species. LAB are deposited in "Microbial Depository Center" (MDC) SPC "Armbiotechnology". Methods: LAB strains were isolated from different dairy products from rural households from the highland regions of Armenia. Serially diluted samples were spread on MRS (Merck, Germany) and hydrolyzed milk agar (1,2 % w/v). Single colonies from each LAB were individually inoculated in liquid MRS medium and incubated at 37oC for 24 hours. Culture broth with biomass was centrifuged at 10,000 g during 20 min for obtaining of cell free culture broth (CFC). The antimicrobial substances from CFC broth were purified by the combination of adsorption-desorption and ion-exchange chromatography methods. Separation of bacteriocins was performed using a HPLC method on "Avex ODS" C18 column. Mass analysis of peptides recorded on the device API 4000 in the electron ionization mode. The spot-on-lawn method on the test culture plated in the solid medium was applied. The antimicrobial activity is expressed in arbitrary units (AU/ml). Results. Purification of CFC broth of LAB allowed to obtain partially purified antimicrobial preparations which contains bacteriocins with broad spectrum of antimicrobial activity. Investigation of their main biochemical properties shown, that inhibitory activity of preparations is partially reduced after treatment with proteinase K, trypsin, pepsin, suggesting a proteinaceous nature of bacteriocin-like substances containing in CFC broth. Preparations preserved their activity after heat treatment (50-121 oC, 20 min) and were stable in the pH range 3–8. The results of SDS PAAG electrophoresis show that L.plantarum 66 and Ent.faecium 64 strains have one bacteriocin (BCN) with maximal antimicrobial activity with approximate molecular weight 2.0-3.0 kDa. From L.rhamnosus 109 two BCNs were obtained. Mass spectral analysis indicates that these bacteriocins have peptide bonds and molecular weight of BCN 1 and BCN 2 are approximately 1.5 kDa and 700 Da. Discussion: Thus, our experimental data shown, that isolated endemic strains of LAB are able to produce bacteriocins with high and different inhibitory activity against broad spectrum of microorganisms of different taxonomic group, such as Salmonella sp., Esherichia coli, Bacillus sp., L.monocytogenes, Proteus mirabilis, Staph. aureus, Ps. aeruginosa. Obtained results proved the perspectives for use of endemic strains in the preservation of foodstuffs. Acknowledgments: This work was realized with financial support of the Project Global Initiatives for Preliferation Prevention (GIPP) T2- 298, ISTC A-1866.

Keywords: antimicrobial activity, bacteriocins, endemic strains, food safety

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Authors: William Michael Short

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Semantic Web’ technologies such as the Unified Medical Language System Metathesaurus, SNOMED-CT, and MeSH have been touted as transformational for the way users access online medical and health information, enabling both the automated analysis of natural-language data and the integration of heterogeneous healthrelated resources distributed across the Internet through the use of standardized terminologies that capture concepts and relationships between concepts that are expressed differently across datasets. However, the approaches that have so far characterized ‘semantic bioinformatics’ have not yet fulfilled the promise of the Semantic Web for medical and health information retrieval applications. This paper argues within the perspective of cognitive linguistics and cognitive anthropology that four features of human meaning-making must be taken into account before the potential of semantic technologies can be realized for this domain. First, many semantic technologies operate exclusively at the level of the word. However, texts convey meanings in ways beyond lexical semantics. For example, transitivity patterns (distributions of active or passive voice) and modality patterns (configurations of modal constituents like may, might, could, would, should) convey experiential and epistemic meanings that are not captured by single words. Language users also naturally associate stretches of text with discrete meanings, so that whole sentences can be ascribed senses similar to the senses of words (so-called ‘discourse topics’). Second, natural language processing systems tend to operate according to the principle of ‘one token, one tag’. For instance, occurrences of the word sound must be disambiguated for part of speech: in context, is sound a noun or a verb or an adjective? In syntactic analysis, deterministic annotation methods may be acceptable. But because natural language utterances are typically characterized by polyvalency and ambiguities of all kinds (including intentional ambiguities), such methods leave the meanings of texts highly impoverished. Third, ontologies tend to be disconnected from everyday language use and so struggle in cases where single concepts are captured through complex lexicalizations that involve profile shifts or other embodied representations. More problematically, concept graphs tend to capture ‘expert’ technical models rather than ‘folk’ models of knowledge and so may not match users’ common-sense intuitions about the organization of concepts in prototypical structures rather than Aristotelian categories. Fourth, and finally, most ontologies do not recognize the pervasively figurative character of human language. However, since the time of Galen the widespread use of metaphor in the linguistic usage of both medical professionals and lay persons has been recognized. In particular, metaphor is a well-documented linguistic tool for communicating experiences of pain. Because semantic medical knowledge-bases are designed to help capture variations within technical vocabularies – rather than the kinds of conventionalized figurative semantics that practitioners as well as patients actually utilize in clinical description and diagnosis – they fail to capture this dimension of linguistic usage. The failure of semantic technologies in these respects degrades the efficiency and efficacy not only of medical research, where information retrieval inefficiencies can lead to direct financial costs to organizations, but also of care provision, especially in contexts of patients’ self-management of complex medical conditions.

Keywords: ambiguity, bioinformatics, language, meaning, metaphor, ontology, semantic web, semantics

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Authors: Tom S. Owens, Tom A. Calverley, Benjamin S. Stacey, Christopher J. Marley, George Rose, Lewis Fall, Gareth L. Jones, Priscilla Williams, John P. R. Williams, Martin Steggall, Damian M. Bailey

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Introduction and aims: Sports-related concussion (SRC) represents a significant and growing public health concern in rugby union, yet remains one of the least understood injuries facing the health community today. Alongside increasing SRC incidence rates, there is concern that prior recurrent concussion may contribute to long-term neurologic sequelae in later-life. This may be due to an accelerated decline in cerebral perfusion, a major risk factor for neurocognitive decline and neurodegeneration, though the underlying mechanisms remain to be established. The present study hypothesised that recurrent concussion in current professional rugby union players would result in elevated systemic oxidative-nitrosative stress, reflected by a free radical-mediated reduction in nitric oxide (NO) bioavailability and impaired cerebrovascular and cognitive function. Methodology: A longitudinal study design was adopted across the 2017-2018 rugby union season. Ethical approval was obtained from the University of South Wales Ethics Committee. Data collection is ongoing, and therefore the current report documents result from the pre-season and first half of the in-season data collection. Participants were initially divided into two subgroups; 23 professional rugby union players (aged 26 ± 5 years) and 22 non-concussed controls (27 ± 8 years). Pre-season measurements were performed for cerebrovascular function (Doppler ultrasound of middle cerebral artery velocity (MCAv) in response to hypocapnia/normocapnia/hypercapnia), cephalic venous concentrations of the ascorbate radical (A•-, electron paramagnetic resonance spectroscopy), NO (ozone-based chemiluminescence) and cognition (neuropsychometric tests). Notational analysis was performed to assess contact in the rugby group throughout each competitive game. Results: 1001 tackles and 62 injuries, including three concussions were observed across the first half of the season. However, no associations were apparent between number of tackles and any injury type (P > 0.05). The rugby group expressed greater oxidative stress as indicated by increased A•- (P < 0.05 vs. control) and a subsequent decrease in NO bioavailability (P < 0.05 vs. control). The rugby group performed worse in the Ray Auditory Verbal Learning Test B (RAVLT-B, learning, and memory) and the Grooved Pegboard test using both the dominant and non-dominant hands (visuomotor coordination, P < 0.05 vs. control). There were no between-group differences in cerebral perfusion at baseline (MCAv: 54 ± 13 vs. 59 ± 12, P > 0.05). Likewise, no between-group differences in CVRCO2Hypo (2.58 ± 1.01 vs. 2.58 ± 0.75, P > 0.05) or CVRCO2Hyper (2.69 ± 1.07 vs. 3.35 ± 1.28, P > 0.05) were observed. Conclusion: The present study identified that the rugby union players are characterized by impaired cognitive function subsequent to elevated systemic-oxidative-nitrosative stress. However, this appears to be independent of any functional impairment in cerebrovascular function. Given the potential long-term trajectory towards accelerated cognitive decline in populations exposed to SRC, prophylaxis to increase NO bioavailability warrants consideration.

Keywords: cognition, concussion, mild traumatic brain injury, rugby

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Authors: Irmak Karaduman, Tugba Corlu, Sezin Galioglu, Burcu Akata, M. Ali Yildirim, Aytunç Ateş, Selim Acar

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Breath analysis represents a promising non-invasive, fast and cost-effective alternative to well-established diagnostic and monitoring techniques such as blood analysis, endoscopy, ultrasonic and tomographic monitoring. Portable, non-invasive, and low-cost breath analysis devices are becoming increasingly desirable for monitoring different diseases, especially asthma. Beacuse of this, NO gas sensing at low concentrations has attracted progressive attention for clinical analysis in asthma. Recently, nanomaterials based sensors are considered to be a promising clinical and laboratory diagnostic tool, because its large surface–to–volume ratio, controllable structure, easily tailored chemical and physical properties, which bring high sensitivity, fast dynamic processand even the increasing specificity. Among various nanomaterials, semiconducting metal oxides are extensively studied gas-sensing materials and are potential sensing elements for breathanalyzer due to their high sensitivity, simple design, low cost and good stability.The sensitivities of metal oxide semiconductor gas sensors can be enhanced by adding noble metals. Doping contents, distribution, and size of metallic or metal oxide catalysts are key parameters for enhancing gas selectivity as well as sensitivity. By manufacturing doping MOS structures, it is possible to develop more efficient sensor sensing layers. Zeolites are perhaps the most widely employed group of silicon-based nanoporous solids. Their well-defined pores of sub nanometric size have earned them the name of molecular sieves, meaning that operation in the size exclusion regime is possible by selecting, among over 170 structures available, the zeolite whose pores allow the pass of the desired molecule, while keeping larger molecules outside.In fact it is selective adsorption, rather than molecular sieving, the mechanism that explains most of the successful gas separations achieved with zeolite membranes. In view of their molecular sieving and selective adsorption properties, it is not surprising that zeolites have found use in a number of works dealing with gas sensing devices. In this study, the Cu doped ZnO nanostructure film was produced by SILAR method and investigated the NO gas sensing properties. To obtain the selectivity of the sample, the gases including CO,NH3,H2 and CH4 were detected to compare with NO. The maximum response is obtained at 85 C for 20 ppb NO gas. The sensor shows high response to NO gas. However, acceptable responses are calculated for CO and NH3 gases. Therefore, there are no responses obtain for H2 and CH4 gases. Enhanced to selectivity, Cu doped ZnO nanostructure film was coated with zeolite A thin film. It is found that the sample possess an acceptable response towards NO hardly respond to CO, NH3, H2 and CH4 at room temperature. This difference in the response can be expressed in terms of differences in the molecular structure, the dipole moment, strength of the electrostatic interaction and the dielectric constant. The as-synthesized thin film is considered to be one of the extremely promising candidate materials in electronic nose applications. This work is supported by The Scientific and Technological Research Council of Turkey (TUBİTAK) under Project No, 115M658 and Gazi University Scientific Research Fund under project no 05/2016-21.

Keywords: Cu doped ZnO, electrical characterization, gas sensing, zeolite

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Authors: Jonas Volungevicius, Kristina Amaleviciute, Rimantas Vaisvalavicius, Alvyra Slepetiene, Darijus Veteikis

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Lithuanian territory is characterized by landscape with prevailing morain hills and clayey lowlands. The largest part of it has endured agrogenization of various degrees which was the cause of changes both in the structure of landscape and soil cover, transformations of soil profile and degradation of natural background soils. These changes influence negatively geoecological potential of landscape and soil and contribute to the weakening of the sustainability of agroecosystems. Research objective: to reveal the landscape agrogenization induced alterations of catenae and their appendant soil profiles in Lithuanian morain hills and clayey lowlands. Methods: Soil cover analysis and catenae charting was conducted using landscape profiling; soil morphology detected and soil type identified following WRB 2014. Granulometric composition of soil profiles was obtained by laser diffraction method (lazer diffractometer Mastersizer 2000). pH was measured in H2O extraction using potentiometric titration; SOC was determined by the Tyurin method modified by Nikitin, measuring with spectrometer Cary 50 (VARIAN) in 590 nm wavelength using glucose standards. Results: analysis showed that the decrease of forest vegetation and the other natural landscape components following the agrogenization of the research area influenced differently but significantly the structural alterations in soil cover and vertical soil profile. The research detected that due to landscape agrogenization, the suppression of zone-specific processes and the intensification of inter-zone processes determined by agrogenic factors take place in Lithuanian agroecosystems. In forested hills historically prevailing Retisols and Histosols territorial complex is transforming into the territorial complex of Regosols, Deluvial soils and drained Histosols. Processes taking place are simplification of vertical profile structure, intensive rejuvenation of profile, disappearance of the features of zone-specific soil-forming processes (podzolization, lessivage, gley formation). Erosion and deluvial processes manifest more intensively and weakly accumulating organic material more intensively spread in a vertical soil profile. The territorial soil complex of Gleyic Luvisols and Gleysols dominating in forested clayey lowlands subjected to agrogenization is transformed into the catena of drained Luvisols and pseudo Cambisols. The best expressed are their changes in moisture regime (morphological features of gley and stagnic properties are on decline) together with alterations of pH and distribution and intensity of accumulation of organic matter in profile. A specific horizon, antraquic, uncharacteristic to natural soil formation is appearing. Important to note that due to deep ploughing and other agrotechnical measures, the natural vertical differentiation of clay particles in a soil profile is destroyed which leads not only to alterations of physical qualities of soil, but also encumbers the identification of Luvisols by creating presumptions to misidentify them as Cambisols. The latter have never developed in these ecosystems under the present climatic conditions. Acknowledgements: This work was supported by the National Science Program: The effect of long-term, different-intensity management of resources on the soils of different genesis and on other components of the agro-ecosystems [grant number SIT-9/2015] funded by the Research Council of Lithuania.

Keywords: agroecosystems, landscape agrogenization, luvisols, retisols, transformation of soil profile

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Authors: E. K. Tripsanas, D. Spanos, I. Oikonomopoulos, K. Stathopoulou, A. S. Abdelsamad, A. Pagoulatos

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Patraikos Gulf is located offshore western Greece, and it is limited to the west by the Zante, Cephalonia, and Lefkas islands. The Plio/Pleistocene sequence is characterized by two depocenters, the east and west Patraikos basins separated from each other by a prominent sill. This study is based on the Plio/Pleistocene seismic stratigraphy analysis of a newly acquired 3D PSDM (Pre-Stack depth migration) seismic survey in the west Patraikos Basin and few 2D seismic profiles throughout the entire Patraikos Gulf. The eastern Patraikos Basin, although completely buried today with water depths less than 100 m, it was a deep basin during Pliocene ( > 2 km of Pliocene-Pleistocene sediments) and appears to have gathered most of Achelous River discharges. The west Patraikos Gulf was shallower ( < 1300 m of Pliocene-Pleistocene sediments) and characterized by a hummocky relief due to thrust-belt tectonics and Miocene to Pleistocene halokinetic processes. The transition from Pliocene to Miocene is expressed by a widespread erosional unconformity with evidence of fluvial drainage patterns. This indicates that west Patraikos Basin was aerially exposed during the Messinian Salinity Crisis. Continuous to semi-continuous, parallel reflections in the lower, early- to mid-Pliocene seismic packet provides evidence that the re-connection of the Mediterranean Sea with the Atlantic Ocean during Zanclean resulted in the flooding of the west Patraikos basin and the domination of hemipelagic sedimentation interrupted by occasional gravity flows. This is evident in amplitude and semblance horizon slices, which clearly show the presence of long-running, meandering submarine channels sourced from the southeast (northwest Peloponnese) and north. The long-running nature of the submarine channels suggests mobile efficient turbidity currents, probably due to the participation of a sufficient amount of clay minerals in their suspended load. The upper seismic section in the study area mainly consists of several successions of clinoforms, interpreted as progradational delta complexes of Achelous River. This sudden change from marine to shallow marine sedimentary processes is attributed to climatic changes and eustatic perturbations since late Pliocene onwards (~ 2.6 Ma) and/or a switch of Achelous River from the east Patraikos Basin to the west Patraikos Basin. The deltaic seismic unit consists of four delta complexes. The first two complexes result in the infill of topographic depressions and smoothing of an initial hummocky bathymetry. The distribution of the upper two delta complexes is controlled by compensational stacking. Amplitude and semblance horizon slices depict the development of several almost straight and short (a few km long) distributary submarine channels at the delta slopes and proximal prodeltaic plains with lobate sand-sheet deposits at their mouths. Such channels are interpreted to result from low-efficiency turbidity currents with low content in clay minerals. Such a differentiation in the nature of the gravity flows is attributed to the switch of the sediment supply from clay-rich sediments derived from the draining of flysch formations of the Ionian and Gavrovo zones, to the draining of poor in clay minerals carbonate formations of Gavrovo zone through the Achelous River.

Keywords: sequence stratigraphy, basin analysis, river deltas, submarine channels

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Authors: Wellemans Isabelle, Remmelink Myriam, Foucart Annick, Rusu Stefan, Compère Christophe

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Primary pulmonary meningioma (PPM) is a very rare tumor, and its occurrence has been reported only sporadically. Multiple PPMs are even more exceptional, and herein, we report, to the best of our knowledge, the fourth case, focusing on the clinicopathological features of the tumor. Moreover, the possible relationship between the use of progesterone–only contraceptives and the development of these neoplasms will be discussed. Case Report: We report a case of a 51-year-old female presenting three solid pulmonary nodules, with the following localizations: right upper lobe, middle lobe, and left lower lobe, described as incidental findings on computed tomography (CT) during a pre-bariatric surgery check-up. The patient revealed no drinking or smoking history. The physical exam was unremarkable except for the obesity. The lesions ranged in size between 6 and 24 mm and presented as solid nodules with lobulated contours. The largest lesion situated in the middle lobe had mild fluorodeoxyglucose (FDG) uptake on F-18 FDG positron emission tomography (PET)/CT, highly suggestive of primary lung neoplasm. For pathological assessment, video-assisted thoracoscopic middle lobectomy and wedge resection of the right upper nodule was performed. Histological examination revealed relatively well-circumscribed solid proliferation of bland meningothelial cells growing in whorls and lobular nests, presenting intranuclear pseudo-inclusions and psammoma bodies. No signs of anaplasia were observed. The meningothelial cells expressed diffusely Vimentin, focally Progesterone receptors and were negative for epithelial (cytokeratin (CK) AE1/AE3, CK7, CK20, Epithelial Membrane Antigen (EMA)), neuroendocrine markers (Synaptophysin, Chromogranin, CD56) and Estrogenic receptors. The proliferation labelling index Ki-67 was low (<5%). Metastatic meningioma was ruled out by brain and spine magnetic resonance imaging (MRI) scans. The third lesion localized in the left lower lobe was followed-up and resected three years later because of its slow but significant growth (14 mm to 16 mm), alongside two new infra centimetric lesions. Those three lesions showed a morphological and immunohistochemical profile similar to previously resected lesions. The patient was disease-free one year post-last surgery. Discussion: Although PPMs are mostly benign and slow-growing tumors with an excellent prognosis, they do not present specific radiological characteristics, and it is difficult to differentiate it from other lung tumors, histopathologic examination being essential. Aggressive behavior is associated with atypical or anaplastic features (WHO grades II–III) The etiology is still uncertain and different mechanisms have been proposed. A causal connection between sexual hormones and meningothelial proliferation has long been suspected and few studies examining progesterone only contraception and meningioma risk have all suggested an association. In line with this, our patient was treated with Levonorgestrel, a progesterone agonist, intra-uterine device (IUD). Conclusions: PPM, defined by the typical histological and immunohistochemical features of meningioma in the lungs and the absence of central nervous system lesions, is an extremely rare neoplasm, mainly solitary and associating, and indolent growth. Because of the unspecific radiologic findings, it should always be considered in the differential diagnosis of lung neoplasms. Regarding multiple PPM, only three cases are reported in the literature, and this is the first described in a woman treated by a progesterone-only IUD to the best of our knowledge.

Keywords: pulmonary meningioma, multiple meningioma, meningioma, pulmonary nodules

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Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas

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Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.

Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib

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Authors: Xue Bai, Ranran He, Chang Liu

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Care planning before the onset of intensive care needs can benefit older adults’ psychological well-being and increases families’ ability to manage caregiving crises and cope with care transitions. Effective care planning requires collaborative ‘team-work’ in families. However, future care planning has not been substantially examined in intergenerational or family contexts, let alone among immigrant families who have to face particular challenges in parental caregiving. From a family systems perspective, this study intends to explore the extent, processes, and contents of intergenerational care planning of Mainland immigrant ageing families in Hong Kong and to examine the intergenerational congruence and discrepancies in the care planning process. Adopting a qualitative research design, semi-structured in-depth interviews were conducted with 17 adult child-older parent pairs and another 33 adult children. In total, 50 adult children who migrated to Hong Kong after the age of 18 with more than three years’ work experience in Hong Kong had at least one parent aged over 55 years old who was not a Hong Kong resident and considered his/herself as the primary caregiver of the parent were recruited. Seventeen ageing parents of the recruited adult children were invited for dyadic interviews. Scarcity of caregiving resources in the context of cross-border migration, intergenerational discrepancies in care planning stages, both generations’ struggle and ambivalence toward filial care, intergenerational transmission of care values, and facilitating role of accumulated family capital in care preparation were primary themes concluded from participants’ narratives. Compared with ageing parents, immigrant adult children generally displayed lower levels of care planning. Although with a strong awareness of parents’ future care needs, few adult children were found engaged in concrete planning activities. This is largely due to their uncertainties toward future life and career, huge work and living pressure, the relatively good health status of their parents, and restrictions of public welfare policies in the receiving society. By contrast, children’s cross-border migration encouraged ageing parents to have early and clear preparation for future care. Ageing parents mostly expressed low filial care expectations when realizing the scarcity of family caregiving resources in the cross-border context. Even though they prefer in-person support from children, most of them prepare themselves for independent ageing to prioritize the next generation’s needs or choose to utilize paid services, welfare systems, friend networks, or extended family networks in their sending society. Adult children were frequently found caught in the dilemma of desiring to provide high quality and in-person support for their parents but lacking sufficient resources. Notably, a salient pattern of intergenerational transmission in terms of family and care values and ideal care arrangement emerged from intergenerational care preparation. Moreover, the positive role of accumulated family capital generated by a reunion in care preparation and joint decision-making were also identified. The findings of the current study will enhance professionals’ and service providers’ awareness of intergenerational care planning in cross-border migration contexts, inform services to alleviate unpreparedness for elderly care and intergenerational discrepancies concerning care arrangements and broaden family services to encompass intergenerational care planning interventions. Acknowledgment: This study is supported by a General Research Grant from the Research Grants Council of the HKSAR, China (Project Number: 15603818).

Keywords: intergenerational care planning, mainland immigrants in Hong Kong, migrant family, older adults

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Authors: Farid Risheq, M. Zaid Alrisheq, Shuaa Al-Sadoon, Karim Al-Faqih, Mays Abdulazeez

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Breast cancer is the most frequently diagnosed cancer worldwide, and a common cause of death among women. Various conventional anatomical imaging tools are utilized for diagnosis, histological assessment and TNM (Tumor, Node, Metastases) staging of breast cancer. Biopsy of sentinel lymph node is becoming an alternative to the axillary lymph node dissection. Advances in 18-Fluoro-Deoxi-Glucose Positron Emission Tomography/Computed Tomography (18FDG-PET/CT) imaging have facilitated breast cancer diagnosis utilizing biological trapping of 18FDG inside lesion cells, expressed as Standardized Uptake Value (SUVmax). Objective: To present the utility of 18FDG uptake PET/CT scans in detecting active extra lymph nodes and distant occult metastases for breast cancer staging. Subjects and Methods: Four female patients were presented with initially classified TNM stages of breast cancer based on conventional anatomical diagnostic techniques. 18FDG-PET/CT scans were performed one hour post 18FDG intra-venous injection of (300-370) MBq, and (7-8) bed/130sec. Transverse, sagittal, and coronal views; fused PET/CT and MIP modality were reconstructed for each patient. Results: A total of twenty four lesions in breast, extended lesions to lung, liver, bone and active extra lymph nodes were detected among patients. The initial TNM stage was significantly changed post 18FDG-PET/CT scan for each patient, as follows: Patient-1: Initial TNM-stage: T1N1M0-(stage I). Finding: Two lesions in right breast (3.2cm2, SUVmax=10.2), (1.8cm2, SUVmax=6.7), associated with metastases to two right axillary lymph nodes. Final TNM-stage: T1N2M0-(stage II). Patient-2: Initial TNM-stage: T2N2M0-(stage III). Finding: Right breast lesion (6.1cm2, SUVmax=15.2), associated with metastases to right internal mammary lymph node, two right axillary lymph nodes, and sclerotic lesions in right scapula. Final TNM-stage: T2N3M1-(stage IV). Patient-3: Initial TNM-stage: T2N0M1-(stage III). Finding: Left breast lesion (11.1cm2, SUVmax=18.8), associated with metastases to two lymph nodes in left hilum, and three lesions in both lungs. Final TNM-stage: T2N2M1-(stage IV). Patient-4: Initial TNM-stage: T4N1M1-(stage III). Finding: Four lesions in upper outer quadrant area of right breast (largest: 12.7cm2, SUVmax=18.6), in addition to one lesion in left breast (4.8cm2, SUVmax=7.1), associated with metastases to multiple lesions in liver (largest: 11.4cm2, SUV=8.0), and two bony-lytic lesions in left scapula and cervicle-1. No evidence of regional or distant lymph node involvement. Final TNM-stage: T4N0M2-(stage IV). Conclusions: Our results demonstrated that 18FDG-PET/CT scans had significantly changed the TNM stages of breast cancer patients. While the T factor was unchanged, N and M factors showed significant variations. A single session of PET/CT scan was effective in detecting active extra lymph nodes and distant occult metastases, which were not identified by conventional diagnostic techniques, and might advantageously replace bone scan, and contrast enhanced CT of chest, abdomen and pelvis. Applying 18FDG-PET/CT scan early in the investigation, might shorten diagnosis time, helps deciding adequate treatment protocol, and could improve patients’ quality of life and survival. Trapping of 18FDG in malignant lesion cells, after a PET/CT scan, increases the retention index (RI%) for a considerable time, which might help localize sentinel lymph node for biopsy using a hand held gamma probe detector. Future work is required to demonstrate its utility.

Keywords: axillary lymph nodes, breast cancer staging, fluorodeoxyglucose positron emission tomography/computed tomography, lymph nodes

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Authors: Leila Noori, Rosario Barone, Francesca Rappa, Antonella Marino Gammazza, Alessandra Maria Vitale, Giuseppe Donato Mangano, Giusy Sentiero, Filippo Macaluso, Kathryn H. Myburgh, Francesco Cappello, Federica Scalia

Abstract:

The neuromuscular system controls, directs, and allows movement of the body through the action of neural circuits, which include motor neurons, sensory neurons, and skeletal muscle fibers. Protein homeostasis of the involved cytotypes appears crucial to maintain the correct and prolonged functions of the neuromuscular system, and both neuronal cells and skeletal muscle fibers express significant quantities of protein chaperones, the molecular machinery responsible to maintain the protein turnover. Genetic mutations or defective post-translational modifications of molecular chaperones (i.e., genetic or acquired chaperonopathies) may lead to neuromuscular disorders called as neurochaperonopathies. The limited knowledge of the effects of the defective chaperones on skeletal muscle fibers and neurons impedes the progression of therapeutic approaches. A distinct genetic variation of CCT5 gene encoding for the subunit 5 of the chaperonin CCT (Chaperonin Containing TCP1; also known as TRiC, TCP1 Ring Complex) was recently described associated with severe distal motor neuropathy by our team. In this study, we investigated the histopathological abnormalities of the skeletal muscle biopsy of the pediatric patient affected by the mutation Leu224Val in the CCT5 subunit. We provide molecular and structural features of the diseased skeletal muscle tissue that we believe may be useful to identify undiagnosed cases of this rare genetic disorder. We investigated the histological abnormalities of the affected tissue via hematoxylin and eosin staining. Then we used immunofluorescence and qPCR techniques to explore the expression and distribution of CCT5 in diseased and healthy skeletal muscle tissue. Immunofluorescence and immunohistochemistry assays were performed to study the sarcomeric and structural proteins of skeletal muscle, including actin, myosin, tubulin, troponin-T, telethonin, and titin. We performed Western blot to examine the protein expression of CCT5 and some heat shock proteins, Hsp90, Hsp60, Hsp27, and α-B crystallin, along with the main client proteins of the CCT5, actin, and tubulin. Our findings revealed muscular atrophy, abnormal morphology, and different sizes of muscle fibers in affected tissue. The swollen nuclei and wide interfiber spaces were seen. Expression of CCT5 had been decreased and showed a different distribution pattern in the affected tissue. Altered expression, distribution, and bandage pattern were detected by confocal microscopy for the interested muscular proteins in tissue from the patient compared to the healthy control. Protein levels of the studied Hsps normally located at the Z-disk were reduced. Western blot results showed increased levels of the actin and tubulin proteins in the diseased skeletal muscle biopsy compared to healthy tissue. Chaperones must be expressed at high levels in skeletal muscle to counteract various stressors such as mechanical, oxidative, and thermal crises; therefore, it seems relevant that defects of molecular chaperones may result in damaged skeletal muscle fibers. So far, several chaperones or cochaperones involved in neuromuscular disorders have been defined. Our study shows that alteration of the CCT5 subunit is associated with the damaged structure of skeletal muscle fibers and alterations of chaperone system components and paves the way to explore possible alternative substrates of chaperonin CCT. However, further studies are underway to investigate the CCT mechanisms of action to design applicable therapeutic strategies.

Keywords: molecular chaperones, neurochaperonopathy, neuromuscular system, protein homeostasis

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Authors: Gertraud Koch, Teresa Stumpf, Alejandra Tijerina García

Abstract:

Discourse analysis research approaches belong to the central research strategies applied throughout the humanities; they focus on the countless forms and ways digital texts and images shape present-day notions of the world. Despite the constantly growing number of relevant digital, multimodal discourse resources, digital humanities (DH) methods are thus far not systematically developed and accessible for discourse analysis approaches. Specifically, the significance of multimodality and meaning plurality modelling are yet to be sufficiently addressed. In order to address this research gap, the D-WISE project aims to develop a prototypical working environment as digital support for the sociology of knowledge approach to discourse analysis and new IT-analysis approaches for the use of context-oriented embedding representations. Playing an essential role throughout our research endeavor is the constant optimization of hermeneutical methodology in the use of (semi)automated processes and their corresponding epistemological reflection. Among the discourse analyses, the sociology of knowledge approach to discourse analysis is characterised by the reconstructive and accompanying research into the formation of knowledge systems in social negotiation processes. The approach analyses how dominant understandings of a phenomenon develop, i.e., the way they are expressed and consolidated by various actors in specific arenas of discourse until a specific understanding of the phenomenon and its socially accepted structure are established. This article presents insights and initial findings from D-WISE, a joint research project running since 2021 between the Institute of Anthropological Studies in Culture and History and the Language Technology Group of the Department of Informatics at the University of Hamburg. As an interdisciplinary team, we develop central innovations with regard to the availability of relevant DH applications by building up a uniform working environment, which supports the procedure of the sociology of knowledge approach to discourse analysis within open corpora and heterogeneous, multimodal data sources for researchers in the humanities. We are hereby expanding the existing range of DH methods by developing contextualized embeddings for improved modelling of the plurality of meaning and the integrated processing of multimodal data. The alignment of this methodological and technical innovation is based on the epistemological working methods according to grounded theory as a hermeneutic methodology. In order to systematically relate, compare, and reflect the approaches of structural-IT and hermeneutic-interpretative analysis, the discourse analysis is carried out both manually and digitally. Using the example of current discourses on digitization in the healthcare sector and the associated issues regarding data protection, we have manually built an initial data corpus of which the relevant actors and discourse positions are analysed in conventional qualitative discourse analysis. At the same time, we are building an extensive digital corpus on the same topic based on the use and further development of entity-centered research tools such as topic crawlers and automated newsreaders. In addition to the text material, this consists of multimodal sources such as images, video sequences, and apps. In a blended reading process, the data material is filtered, annotated, and finally coded with the help of NLP tools such as dependency parsing, named entity recognition, co-reference resolution, entity linking, sentiment analysis, and other project-specific tools that are being adapted and developed. The coding process is carried out (semi-)automated by programs that propose coding paradigms based on the calculated entities and their relationships. Simultaneously, these can be specifically trained by manual coding in a closed reading process and specified according to the content issues. Overall, this approach enables purely qualitative, fully automated, and semi-automated analyses to be compared and reflected upon.

Keywords: entanglement of structural IT and hermeneutic-interpretative analysis, multimodality, plurality of meaning, sociology of knowledge approach to discourse analysis

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