Gene and MicroRNA Expression Profile Changes in ISS Crewmembers Blood Samples

In space, living organisms are exposed to multiple stress factors including microgravity and space radiation. For humans, these harmful environmental factors have been known to cause negative health impacts such as immune dysfunction. Understanding the mechanisms by which spaceflight impacts human health at the molecular level is critical not only for accurately assessing the risks associated with spaceflight, but also for developing effective countermeasures. This study is part of the Functional Immune Project, intended to determine alterations in crewmember immunobiology before, during, and after spaceflight. It emphasizes the study of DNA damage in the ISS crewmembers peripheral blood mononuclear cells (PBMCs), expression patterns of damage-response and inflammatory process genes, and changes in latent virus reactivation biomarkers

Rule By Example: Harnessing Logical Rules for Explainable Hate Speech Detection

Classic approaches to content moderation typically apply a rule-based heuristic approach to flag content. While rules are easily customizable and intuitive for humans to interpret, they are inherently fragile and lack the flexibility or robustness needed to moderate the vast amount of undesirable content found online today. Recent advances in deep learning have demonstrated the promise of using highly effective deep neural models to overcome these challenges. However, despite the improved performance, these data-driven models lack transparency and explainability, often leading to mistrust from everyday users and a lack of adoption by many platforms. In this paper, we present Rule By Example (RBE): a novel exemplar-based contrastive learning approach for learning from logical rules for the task of textual content moderation. RBE is capable of providing rule-grounded predictions, allowing for more explainable and customizable predictions compared to typical deep learning-based approaches. We demonstrate that our approach is capable of learning rich rule embedding representations using only a few data examples. Experimental results on 3 popular hate speech classification datasets show that RBE is able to outperform state-of-the-art deep learning classifiers as well as the use of rules in both supervised and unsupervised settings while providing explainable model predictions via rule-grounding.Comment: ACL 2023 Main Conferenc

Association between metabolically healthy obesity and risk of atrial fibrillation:taking physical activity into consideration

The modification of physical activity (PA) on the metabolic status in relation to atrial fibrillation (AF) in obesity remains unknown. We aimed to investigate the independent and joint associations of metabolic status and PA with the risk of AF in obese population. Based on the data from UK Biobank study, we used Cox proportional hazards models for analyses. Metabolic status was categorized into metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO). PA was categorized into four groups according to the level of moderate-to-vigorous PA (MVPA): none, low, medium, and high. A total of 119,424 obese participants were included for analyses. MHO was significantly associated with a 35% reduced AF risk compared with MUO (HR = 0.65, 95% CI: 0.57–0.73). No significant modification of PA on AF risk among individuals with MHO was found. Among the MUO participants, individuals with medium and high PA had significantly lower AF risk compared with no MVPA (HR = 0.84, 95% CI: 0.74–0.95, and HR = 0.87, 95% CI: 0.78–0.96 for medium and high PA, respectively). As the severity of MUO increased, the modification of PA on AF risk was elevated accordingly. To conclude, MHO was significantly associated with a reduced risk of AF when compared with MUO in obese participants. PA could significantly modify the relationship between metabolic status and risk of AF among MUO participants, with particular benefits of PA associated with the reduced AF risk as the MUO severity elevated. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12933-022-01644-z

A Stepwise, Pilot Study of Bovine Colostrum to Supplement the First Enteral Feeding in Preterm Infants (Precolos):Study Protocol and Initial Results

STUDY PROTOCOL: The optimal feeding for preterm infants during the first weeks is still debated, especially when mother’s own milk is lacking or limited. Intact bovine colostrum (BC) contains high amounts of protein, growth factors, and immuno-regulatory components that may benefit protein intake and gut maturation. We designed a pilot study to investigate the feasibility and tolerability of BC as the first nutrition for preterm infants. The study was designed into three phases (A, B, and C) and recruited infants with birth weights of 1,000–1,800 g (China) or gestational ages (GAs) of 27 + 0 to 32 + 6 weeks (Denmark). In phase A, three infants were recruited consecutively to receive BC as a supplement to standard feeding. In phase B, seven infants were recruited in parallel. In phase C (not yet complete), 40 infants will be randomized to BC or standard feeding. Feeding intolerance, growth, time to full enteral feeding, serious infections/NEC, plasma amino acid profile, blood biochemistry, and intestinal functions are assessed. This paper presents the study protocol and results from phases A and B. RESULTS: Seven Danish and five Chinese infants received 22 ± 11 and 22 ± 6 ml·kg(−1)·day(−1) BC for a mean of 7 ± 3 and 7 ± 1 days which provided 1.81 ± 0.89 and 1.83 ± 0.52 g·kg(−1)·day(−1) protein, respectively. Growth rates until 37 weeks or discharge were in the normal range (11.8 ± 0.9 and 12.9 ± 2.7 g·kg(−1)·day(−1) in Denmark and China, respectively). No clinical adverse effects were observed. Five infants showed a transient hypertyrosinemia on day 7 of life. DISCUSSION AND CONCLUSION: The three-phased study design was used to proceed with caution as this is the first trial to investigate intact BC as the first feed for preterm infants. BC supplementation appeared well tolerated and resulted in high enteral protein intake. Based on the safety evaluation of phases A and B, the randomized phase C has been initiated. When complete, the Precolos trial will document whether it is feasible to use BC as a novel, bioactive milk diet for preterm infants. Our trial paves the way for a larger randomized controlled trial on using BC as the first feed for preterm infants with insufficient access to mother’s own milk

Antimicrobial properties of Pseudomonas strains producing the antibiotic mupirocin

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Activation of PI3-Kinase Is Required for AMPA Receptor Insertion during LTP of mEPSCs in Cultured Hippocampal Neurons

AbstractHippocampal CA1 homosynaptic long-term potentiation (LTP) is expressed specifically at activated synapses. Increased insertion of postsynaptic α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptors (AMPARs) appears to be crucial for CA1 LTP. However, the mechanism underlying AMPAR insertion during LTP remains largely unknown. We now report that phosphatidylinositol 3-kinase (PI3K) is complexed with AMPARs at synapses and activated by selective stimulation of synaptic N-methyl-D-aspartate (NMDA) receptors. Activation of the AMPAR-associated PI3K is required for the increased cell surface expression of AMPARs and LTP. Thus, our results strongly suggest that the AMPAR-PI3K complex may constitute a critical molecular signal responsible for AMPAR insertion at activated CA1 synapses during LTP, and consequently, this lipid kinase may serve to determine the polarity of NMDA receptor-dependent synaptic plasticity

Sarcoma and the 100,000 Genomes Project: our experience and changes to practice

The largest whole genome sequencing (WGS) endeavour involving cancer and rare diseases was initiated in the UK in 2015 and ran for 5 years. Despite its rarity, sarcoma ranked third overall among the number of patients' samples sent for sequencing. Herein, we recount the lessons learned by a specialist sarcoma centre that recruited close to 1000 patients to the project, so that we and others may learn from our experience. WGS data was generated from 597 patients, but samples from the remaining approximately 400 patients were not sequenced. This was largely accounted for by unsuitability due to extensive necrosis, secondary to neoadjuvant radiotherapy or chemotherapy, or being placed in formalin. The number of informative genomes produced was reduced further by a PCR amplification step. We showed that this loss of genomic data could be mitigated by sequencing whole genomes from needle core biopsies. Storage of resection specimens at 4 °C for up to 96 h overcame the challenge of freezing tissue out of hours including weekends. Removing access to formalin increased compliance to these storage arrangements. With over 70 different sarcoma subtypes described, WGS was a useful tool for refining diagnoses and identifying novel alterations. Genomes from 350 of the cohort of 597 patients were analysed in this study. Overall, diagnoses were modified for 3% of patients following review of the WGS findings. Continued refinement of the variant-calling bioinformatic pipelines is required as not all alterations were identified when validated against histology and standard of care diagnostic tests. Further research is necessary to evaluate the impact of germline mutations in patients with sarcoma, and sarcomas with evidence of hypermutation. Despite 50% of the WGS exhibiting domain 1 alterations, the number of patients with sarcoma who were eligible for clinical trials remains small, highlighting the need to revaluate clinical trial design

Integrated Transcriptomics, Metabolomics, and Lipidomics Profiling in Rat Lung, Blood, and Serum for Assessment of Laser Printer-Emitted Nanoparticle Inhalation Exposure-Induced Disease Risks

settings Open AccessArticle Integrated Transcriptomics, Metabolomics, and Lipidomics Profiling in Rat Lung, Blood, and Serum for Assessment of Laser Printer-Emitted Nanoparticle Inhalation Exposure-Induced Disease Risks by Nancy Lan Guo 1,*,Tuang Yeow Poh 2,Sandra Pirela 3,Mariana T. Farcas 4,Sanjay H. Chotirmall 2,Wai Kin Tham 5,Sunil S. Adav 5,Qing Ye 1,Yongyue Wei 6,Sipeng Shen 2,David C. Christiani 2,Kee Woei Ng 3,7,8,Treye Thomas 9,Yong Qian 4 andPhilip Demokritou 3 1 West Virginia University Cancer Institute/School of Public Health, West Virginia University, Morgantown, WV 26506, USA 2 Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore 3 Center for Nanotechnology and Nanotoxicology, Department of Environmental Health, T. H. Chan School of Public Health, Harvard University, Boston, MA 02115, USA 4 Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA 5 Singapore Phenome Centre, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 636921, Singapore 6 Key Lab for Modern Toxicology, Department of Epidemiology and Biostatistics and Ministry of Education (MOE), School of Public Health, Nanjing Medical University, Nanjing 210029, China 7 School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798, Singapore 8 Environmental Chemistry and Materials Centre, Nanyang Environment & Water Research Institute, Singapore 637141, Singapore 9 Office of Hazard Identification and Reduction, U.S. Consumer Product Safety Commission, Rockville, MD 20814, USA * Author to whom correspondence should be addressed. Int. J. Mol. Sci. 2019, 20(24), 6348; https://doi.org/10.3390/ijms20246348 Received: 2 December 2019 / Revised: 12 December 2019 / Accepted: 13 December 2019 / Published: 16 December 2019 (This article belongs to the Special Issue Advances in Nanostructured Materials between Pharmaceutics and Biomedicine) Download PDF Browse Figures Review Reports Cite This Paper Abstract Laser printer-emitted nanoparticles (PEPs) generated from toners during printing represent one of the most common types of life cycle released particulate matter from nano-enabled products. Toxicological assessment of PEPs is therefore important for occupational and consumer health protection. Our group recently reported exposure to PEPs induces adverse cardiovascular responses including hypertension and arrythmia via monitoring left ventricular pressure and electrocardiogram in rats. This study employed genome-wide mRNA and miRNA profiling in rat lung and blood integrated with metabolomics and lipidomics profiling in rat serum to identify biomarkers for assessing PEPs-induced disease risks. Whole-body inhalation of PEPs perturbed transcriptional activities associated with cardiovascular dysfunction, metabolic syndrome, and neural disorders at every observed time point in both rat lung and blood during the 21 days of exposure. Furthermore, the systematic analysis revealed PEPs-induced transcriptomic changes linking to other disease risks in rats, including diabetes, congenital defects, auto-recessive disorders, physical deformation, and carcinogenesis. The results were also confirmed with global metabolomics profiling in rat serum. Among the validated metabolites and lipids, linoleic acid, arachidonic acid, docosahexanoic acid, and histidine showed significant variation in PEPs-exposed rat serum. Overall, the identified PEPs-induced dysregulated genes, molecular pathways and functions, and miRNA-mediated transcriptional activities provide important insights into the disease mechanisms. The discovered important mRNAs, miRNAs, lipids and metabolites may serve as candidate biomarkers for future occupational and medical surveillance studies. To the best of our knowledge, this is the first study systematically integrating in vivo, transcriptomics, metabolomics, and lipidomics to assess PEPs inhalation exposure-induced disease risks using a rat model

Formation of European Integration Development Strategy of Ukraine

Podorozhnii, E. Formation of European integration development strategy of Ukraine / Yevhen Podorozhnii, Sandra Boldizhar, Olexandr Sofilkanich // Baltic Journal of Economic Studies. - 2018. - Vol 4., No 1. - Р. 283–292. - DOI: https://doi.org/10.30525/2256-0742/2018-4-1-283-292.Podorozhnii, Y., Boldizhar, S., & Sofilkanich, O. (2018). FORMATION OF EUROPEAN INTEGRATION DEVELOPMENT STRATEGY OF UKRAINE. Baltic Journal of Economic Studies, 4(1), 283-292. https://doi.org/10.30525/2256-0742/2018-4-1-283-292Сьогодні євроінтеграція - це стратегічний курс України, швидкість якого збільшується. Це зобов'язує звернути увагу на наслідки європейської інтеграції. Європейська інтеграція, тобто формування і подальше зміцнення зв'язків з європейськими країнами, носить комплексний характер. Актуальність теми статті визначається об'єктивним характером європейського інтеграційного процесу в українській економіці і комплексністю наслідків цього процесу. Метою статті є аналіз впливу процесу європейської інтеграції на економічний розвиток країни на основі сценарного підходу.Today European integration is a strategic course of Ukraine, its speed increases. It obliges to pay attention to the consequences of European integration. European integration, that is, formation and further strengthening of ties with European countries, has a complex nature (economic, political, social, cultural, etc.) at all levels – transnational, interregional, between separate economic entities. The relevance of the article’s topic is determined by objective nature of European integration process in Ukrainian economy and complex nature of consequences of this process. The purpose of the article is the analysis of the influence of European integration process on the economic development of the country on the basis of scenario approach. The presence of essential regional imbalances in the socio-economic development in Ukraine requires differentiated approaches to the elaboration of development measures aimed at promoting the creation of free trade area, as well as strengthening economic and sectoral cooperation between Ukraine and the EU. Thus, there appears a necessity to monitor and evaluate progress of economic reforms in regions of Ukraine in the context of European integration processes in order to reveal strengths and weaknesses, to substantiate priorities and means of their achievement, as well as possibility of their timely adjustment for improving the region’s ability to follow the vector of European integration. For the purpose implementation, it seems most appropriate to calculate an integral value – European Integration Index (Ір). In the most general terms, the index is a relative magnitude, designed to fulfil the role of a generalized measure of a certain phenomenon, which is formed under the influence of heterogeneous components, which cannot be directly summed up. European integration consequences for the economy of Ukraine are considered and it is shown that these consequences can have not only a positive nature in the form of new opportunities and open markets but also pose a threat. Scenarios for changing the national economy of Ukraine as a result of the influence of European integration processes are determined. A description for each of these scenarios is provided. Assessment of such scenarios is done according to criteria of desirability, probability, and time of realization. A relation between the considered scenarios for changing the national economy of Ukraine over the influence of European integration processes taking into account probabilistic cause-and-effect relationships between individual scenarios is shown. Consequences of these scenarios for the economic development of Ukraine are presented. The research result is the detection and characteristic of scenarios of changes in the economy of Ukraine as a result of the influence of European integration processes, as well as the characteristic of the influence of such scenarios on the country’s economic development. Scientific novelty of research results is defining scenarios of changes in Ukrainian economy under the influence of European integration processes, characteristics of these scenarios and relations among them taking into account the influence of such scenarios on the country’s economic security. The practical value of research results is considered a possibility to provide adaptation of regions of Ukraine to the consequences of European integration processes in the economic and legal field.Сегодня евроинтеграция - это стратегический курс Украины, скорость которого увеличивается. Это обязывает обратить внимание на последствия европейской интеграции. Европейская интеграция, то есть формирование и дальнейшее укрепление связей с европейскими странами, носит комплексный характер. Актуальность темы статьи определяется объективным характером европейского интеграционного процесса в украинской экономике и комплексностью последствий этого процесса. Целью статьи является анализ влияния процесса европейской интеграции на экономическое развитие страны на основе сценарного подхода

Genome-wide Maps of Nuclear Lamina Interactions in Single Human Cells

Mammalian interphase chromosomes interact with the nuclear lamina (NL) through hundreds of large lamina-associated domains (LADs). We report a method to map NL contacts genome-wide in single human cells. Analysis of nearly 400 maps reveals a core architecture consisting of gene-poor LADs that contact the NL with high cell-to-cell consistency, interspersed by LADs with more variable NL interactions. The variable contacts tend to be cell-type specific and are more sensitive to changes in genome ploidy than the consistent contacts. Single-cell maps indicate that NL contacts involve multivalent interactions over hundreds of kilobases. Moreover, we observe extensive intra-chromosomal coordination of NL contacts, even over tens of megabases. Such coordinated loci exhibit preferential interactions as detected by Hi-C. Finally, the consistency of NL contacts is inversely linked to gene activity in single cells and correlates positively with the heterochromatic histone modification H3K9me3. These results highlight fundamental principles of single-cell chromatin organization.National Institutes of Health (U.S.) (Grant R01 GM114190)National Human Genome Research Institute (U.S.) (Grant R01 HG003143