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Mast cells differentiated in synovial fluid and resident in osteophytes exalt the inflammatory pathology of osteoarthritis
Get PDFIntroduction: Osteophytes are a prominent feature of osteoarthritis (OA) joints and one of the clinical hallmarks of the disease progression. Research on osteophytes is fragmentary and modes of its contribution to OA pathology are obscure. Aim: To elucidate the role of osteophytes in OA pathology from a perspective of molecular and cellular events. Methods: RNA-seq of fully grown osteophytes, collected from tibial plateau of six OA patients revealed patterns corresponding to active extracellular matrix re-modulation and prominent participation of mast cells. Presence of mast cells was further confirmed by immunohistochemistry, performed on the sections of the osteophytes using anti-tryptase alpha/beta-1 and anti-FC epsilon RI antibodies and the related key up-regulated genes were validated by qRT-PCR. To test the role of OA synovial fluid (SF) in mast cell maturation as proposed by the authors, hematopoietic stem cells (HSCs) and ThP1 cells were cultured in a media supplemented with 10% SF samples, obtained from various grades of OA patients and were monitored using specific cell surface markers by flow cytometry. Proteomics analysis of SF samples was performed to detect additional markers specific to mast cells and inflammation that drive the cell differentiation and maturation. Results: Transcriptomics of osteophytes revealed a significant upregulation of mast cells specific genes such as chymase 1 (CMA1; 5-fold) carboxypeptidase A3 (CPA3; 4-fold), MS4A2/FCERI (FCERI; 4.2-fold) and interleukin 1 receptor-like 1 (IL1RL1; 2.5-fold) indicating their prominent involvement. (In IHC, anti-tryptase alpha/beta-1 and anti- FC epsilon RI-stained active mast cells were seen populated in cartilage, subchondral bone, and trabecular bone.) Based on these outcomes and previous learnings, the authors claim a possibility of mast cells invasion into osteophytes is mediated by SF and present in vitro cell differentiation assay results, wherein ThP1 and HSCs showed differentiation into HLA-DR+/CD206+ and FCERI+ phenotype, respectively, after exposing them to medium containing 10% SF for 9 days. Proteomics analysis of these SF samples showed an accumulation of mast cell-specific inflammatory proteins. Conclusions: RNA-seq analysis followed by IHC study on osteophyte samples showed a population of mast cells resident in them and may further accentuate inflammatory pathology of OA. Besides subchondral bone, the authors propose an alternative passage of mast cells invasion in osteophytes, wherein OA SF was found to be necessary and sufficient for maturation of mast cell precursor into effector cells
MEDAS: an open-source platform as a service to help break the walls between medicine and informatics
No full textIn the past decade, deep learning (DL) has achieved unprecedented success in numerous fields, such as computer vision and healthcare. Particularly, DL is experiencing an increasing development in advanced medical image analysis applications in terms of segmentation, classification, detection, and other tasks. On the one hand, tremendous needs that leverage DL’s power for medical image analysis arise from the research community of a medical, clinical, and informatics background to share their knowledge, skills, and experience jointly. On the other hand, barriers between disciplines are on the road for them, often hampering a full and efficient collaboration. To this end, we propose our novel open-source platform, i.e., MEDAS–the MEDical open-source platform As Service. To the best of our knowledge, MEDAS is the first open-source platform providing collaborative and interactive services for researchers from a medical background using DL-related toolkits easily and for scientists or engineers from informatics modeling faster. Based on tools and utilities from the idea of RINV (Rapid Implementation aNd Verification), our proposed platform implements tools in pre-processing, post-processing, augmentation, visualization, and other phases needed in medical image analysis. Five tasks, concerning lung, liver, brain, chest, and pathology, are validated and demonstrated to be efficiently realizable by using MEDAS
Impacts of COVID-19 on Sustainable Development Goals and effective approaches to maneuver them in the post-pandemic environment
No full textIn the pursuit of constructing a sustainable world for all through the instrumental seventeen Sustainable Development Goals, the COVID-19 pandemic emerged and affected the efforts concentrated on these goals. Therefore, there is a pressing need to analyze the extent of the impact that unfolded from the pandemic on each Sustainable Development Goal and further to direct the post-pandemic situation to accelerate the progress in every goal. Besides, there exists a knowledge gap in understanding the Sustainable Development Goals and its interaction with each goal through synergic and trade-off effects. To address the aforementioned imperative problems, this study is formulated to perform an impact assessment as well as to provide direction in the post-pandemic environment to effectively progress towards the Sustainable Development Goals by using a hybrid qualitative and quantitative framework. A detailed investigation is carried out to examine the pandemic impacts in every goal, and a quantified impact analysis is performed in terms of the targets of the Sustainable Development Goals with the aid of ranking methodology. The results indicate that SDG 1 and SDG 8 are the most impacted goal. To provide deeper perspectives into the Sustainable Development Goals, a critical analysis of the targets and indicators is performed to characterize the goals from their elemental point of view, such as nature of goals, depending factors, locus of the goal, and Sustainable Development Goal interactions. Further, a novel parameter, the degree of randomness, is proposed whose application in environmental research is immense. The impact on each goal and impact interaction between all the SDGs are also mapped, through which the dynamics of Sustainable Development Goal interactions is elaborated. In context with the post-pandemic scenario, the strategies to achieve the Sustainable Development Goals with environmental focus are presented with prioritization factor that supports quick recovery. The introduced prioritization factor is formulated by employing a multi-criteria analysis methodology. In addition, the fundamental elements of SDGs are built upon one another to frame an optimized and effective approach to achieving the SDGs in the post-pandemic environment. Despite the strategies, a conceptual framework to align the business practices with the SDGs is propounded. This study deep down would provide a unique perspective to the research community and would impart deeper knowledge in connection with sustainability, while the solutions framed would steer the policy and decision-makers
Bone diagenesis in the marine environment‐I: Characterization and distribution of trace elements in terrestrial mammalian bones recovered from historic shipwrecks
No full textUnlike the chemical composition and diagenetic modification of buried bones, subaqueous archaeological bone diagenesis has not been studied in detail. This observational work presents a macroscopic and microscopic characterization of 11 variably preserved archaeological terrestrial mammalian bones submerged in seawater and/or surrounded by marine sediment for 169–347 years. In situ trace element analysis was undertaken to identify geochemical fingerprints of diagenesis. The analyzed bones belong to a collection of underwater archaeological faunal materials excavated from four shipwreck sites. With one exception, all archaeological bones were fragmented, some were also heavily stained, and in two samples, the damage to the cortical layer was extensive. Bioerosion was assessed by scanning electron microscopy (SEM), and bone trace element chemistry (by laser ablation inductively coupled mass spectrometry—LA-ICP-MS) was compared with that of an unsubmerged modern sheep bone control. In the control, several trace elements were low in concentration (weighted mean concentration <1 ppm; Cr, Co, Ni, Cu, Y, rare earth elements, Th, U). In the submerged archaeological bones, the weighted mean concentration of Li, Cr, Cu, and U was enriched relative to the modern sheep bone, whereas Rb and Ba were depleted. The best-preserved bone, recovered from Batavia, showed less variation in trace element patterns compared with the more poorly preserved bones. The only archaeological bone with preserved macroscopic structure and cortex showed a gradual decrease in trace element concentration from the outer surface towards the medullary cavity, whereas in samples where more cortical damage was noted, the distribution of these elements is more irregular. With the exception of Cu and Cr, the elements focused on in this work (Li, U, Rb, and Ba) are nonessential to life, supported by their low concentration in the modern sheep bone (with the exception of Ba). The results suggest that early macroscopic and microscopic diagenetic alteration influences the concentration and distribution of chemical elements in submerged bones and that in situ trace element analysis provides clues for the reconstruction of taphonomic trajectories
The Video Classification of Intubation (VCI) score: A new description tool for tracheal intubation using videolaryngoscopy - A pilot study
No full textClostridioides (Clostridium) difficile isolated from paediatric patients in Western Australia 2019–2020
No full textLess is understood about the epidemiology of Clostridioides difficile infection (CDI) in children compared to adults, and its impact is complicated by variations in the natural development of infection in paediatric patients. The interplay of rising CDI incidence in hospitalised paediatric patients, emergence of hypervirulent strains and community associated CDI (CA-CDI) in the past decade is a potential threat in both hospital and community settings. Research in Australia regarding paediatric CDI is limited. Here, we report the molecular characterisation of C. difficile isolated from paediatric patients at a tertiary hospital in Perth, Western Australia. A total of 427 stool samples was collected from patients aged from <1 to 17 years being investigated for diarrhoea from July 2019 to June 2020. Stool specimens were cultured and isolates of C. difficile characterised by ribotyping and toxin gene profiling. Clostridioides difficile was recovered from 84/427 (19.7%) samples tested. The most prevalent PCR ribotypes (RTs) were RT 002 (12.4%), a toxigenic strain, and RT 009 (15.7%), a non-toxigenic strain. Interestingly, C. difficile RT 078 and RT 017, strains that are not endemic in Australia, were isolated from a 1- and 4-year-old child, respectively. Clostridioides difficile RT 106, a strain of emerging importance in Australia, was recovered from two cases (5.3%). Resistance to metronidazole, fidaxomicin, amoxicillin, rifaximin and meropenem was not detected, however, 45 isolates (50.6%) showed resistance to at least one agent, and multidrug resistance was observed in 13.3% of the resistant isolates (6/45). This study provides a baseline for future surveillance of paediatric CDI in Australia. Given that young children can be asymptomatically colonised with toxigenic C. difficile strains, they represent a potential reservoir of strains causing CDI in adults
Drug-Induced Hypersensitivity Syndrome (DIHS)/ Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS): Clinical Features and Pathogenesis
No full textDrug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DIHS/DRESS) is one example of a severe delayed T-cell mediated adverse drug reaction. DIHS/DRESS presents with fever, widespread rash and facial edema, organ involvement, and hematological abnormalities, including eosinophilia and atypical lymphocytosis. DIHS/DRESS is associated with relapse 2-4 weeks following acute symptoms, often coinciding with reactivation of prevalent chronic persistent human Herpesviruses (HHV) such as HHV-6, Epstein-Barr Virus, and cytomegalovirus (CMV). The mortality of DIHS/DRESS is up to 10% and often related to unrecognized myocarditis and CMV complications, with longer-term consequences that contribute to morbidity including autoimmune diseases such as thyroiditis. It is essential that all potential drug causes, including all new drugs introduced within the 8 weeks preceding onset of DIHS/DRESS symptoms, are identified. All potential drug culprits, as well as drugs that are closely related structurally to the culprit drug, should be avoided in the future. Systemic corticosteroids have remained the mainstay for the treatment of DIHS/DRESS with internal organ involvement. Steroid sparing agents, such as cyclosporine, mycophenolate mofetil, and monthly intravenous immune globulin, have been successfully used for treatment, and careful follow-up for CMV reactivation is recommended. Strong associations between HLA class I alleles and DIHS/DRESS predisposition include HLA-B*13:01 and dapsone, HLA-B*58:01 and allopurinol, and HLA-B*32:01 and vancomycin. These have opened a pathway for prevention, risk stratification, and earlier diagnosis. Single-cell sequencing and other studies of immunopathogenesis promise to identify targeted treatment approaches
Blockchain-based random auditor committee for integrity verification
No full textWith the popularity of cloud storage, integrity verification for outsourced data has attracted more and more attention. The majority of existing research works rely on a unique third-party auditor (TPA) or fixed TPAs to audit the integrity of outsourced data, and thus they are vulnerable to DoS and collusion attacks as the TPA is not completely trusted. To conquer this problem, a blockchain-based random auditor committee is proposed to replace the fixed TPAs for the integrity verification (call BRAC scheme for short). The proposed blockchain consensus algorithm utilizes a verifiable random function (VRF) to select the third-party auditor committee (TPAC) which performs contract verification. The leader of TPAs (LTPA) packs the verification proof into a blockchain called verification chain. The main idea is employing the output of a VRF for leader election to make it probabilistic, such that specific nodes cannot be targeted in advance and a certain fraction of the nodes being malicious can be tolerated. We present rigorous security analysis to demonstrate the security of the proposed scheme. Meanwhile, the comprehensive performance evaluation shows that the proposed scheme improves the performance of data integrity verification effectively
Genetic dissection of the mixing properties of wheat flour (Triticum aestivum L.) using unconditional and conditional QTL mapping
Get PDFWheat (Triticum aestivum L.) flour mixing properties are essential quality parameters in the dough development process. Limited research on superior alleles for mixing properties has restricted their molecular improvement, and other factors related to the complex traits have been ignored. A molecular map of 9576 polymorphic markers in the RIL population (F8:9) (Shannong01-35/Gaocheng9411) was constructed to evaluate mixing property effects in three environments. The parents were selected with markedly distinct high-molecular-weight glutenin subunits (HMW-GS). This study not only evaluated mixing properties using conventional unconditional QTL mapping but also evaluated the relationships between protein-related traits using conditional QTL mapping. The analyses identified most additive QTLs for major mixing properties on chromosomes 1A, 1B, and 1D. Two major loci (1A.1-15 and 1D-1) associated with mixing properties have confirmed the important contributions of Glu-A1 and Glu-D1 to wheat quality at the QTL level, which were mainly affected by the gluten index. Another important locus, 1B.1-24 (associated with midline peak value and midline peak width, with high phenotypic variations explained), might represent a new variation distinct from Glu-B1. The favored alleles came from Gaocheng9411. Several mixing properties shared the same QTLs (1B.1-6 and 1A.1-15), indicating tight linkage or pleiotropism. Genotype-by-environment (G×E) interactions were also investigated in the present study. The QTL results in our study may improve our understanding of the genetic interrelationships between mixing properties and protein-related traits
Response of aphid parasitoids to volatile organic compounds from undamaged and infested Brassica oleracea with Myzus persicae
Get PDFHeadspace solid microextraction (HS-SPME) and GC-MS were used to investigate volatile organic compounds (VOCs) from cabbage plants infested and uninfested with green peach aphid Myzus persicae. The HS-SPME combined with GC-MS analysis of the volatiles described the differences between the infested and uninfested cabbage. Overall, 28 compounds were detected in infested and uninfested cabbage. Some VOCs released from infested cabbage were greater than uninfested plants and increased the quantity of the composition from infested plants. According to the peak area from the GC-MS analysis, the VOCs from infested cabbage consisted of propane, 2-methoxy, alpha- and beta pinene, myrcene, 1-hexanone, 5-methyl-1-phenyl-, limonene, decane, gamma-terpinen and heptane, 2,4,4-trimethyl. All these volatiles were higher in the infested cabbage compared with their peak area in the uninfested cabbage. The results of the study using a Y-shape olfactometer revealed that the VOCs produced by infested cabbage attracted Myzus persicae substantially more than uninfested plants or clean air. The percentage of aphid choice was 80% in favor of infested cabbage; 7% were attracted to the clean air choice and uninfested plants. A total of aphids 7% were attracted to clean air. Comparing between infested and uninfested cabbage plants, the aphid was attracted to 63% of the infested cabbage, versus 57% of the uninfested cabbage. The preferences of Aphidus colemani and Aphelinus abdominalis to the infested or uninfested plants with M. persicae and compared with clean air indicated that parasitoids could discriminate the infested cabbage. Both parasitoids significantly responded to the plant odor and were attracted to 86.6% of the infested cabbage plants