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Abstract High altitude acclimatization and disease have been the centerpiece of investigations concerning human health at high altitude. Almost all investigations have focused on either understanding and ameliorating high altitude disease or finding better methods of acclimatization/training at high altitude. The aspect of altitude de-induction/de-acclimatization has remained clouded despite the fact that it was documented since the first decade of twentieth century. A few recent studies, particularly in China, have stated unanimously that high altitude de-acclimatization involved multiple observable clinical symptoms ranging from headache to abdominal distention. These symptoms have been collectively referred to as “high altitude de-acclimatization syndrome” (HADAS). However, computational omics and network biology centric investigations concerning HADAS are nascent. In this study, we focus on the quantitative proteo-informatics, especially network biology, of human plasma proteome in individuals who successfully descended from high altitude areas after a stay of 120 days. In brief, the protein list was uploaded into STRING and IPA to compute z-score based cut-offs which were used to analyze the directionality and significance of various identified protein networks as well as the proteins within them. Relevant upstream regulators extracted using computational strategies were also validated. Time-points till the 180th day of de-induction have been investigated to comparatively assess the changes in the plasma proteome and protein pathways of such individuals since the 7th day of arrival at altitude. Our investigation revealed extensive effects of de-induction on lipid metabolism, inflammation and innate immune system as well as coagulation system. This novel study provides a conceptual framework for formulating therapeutic strategies to ease the symptoms of HADAS during de-acclimatization. Such strategies should focus on normalization of lipid metabolism, inflammatory signaling and coagulation systems.

Abstract Millions of people worldwide visit, live or work in the hypoxic environment encountered at high altitudes and it is important to understand the biomolecular responses to this stress. This would help design mitigation strategies for high altitude illnesses. In spite of a number of studies spanning over 100 years, still the complex mechanisms controlling acclimatization to hypoxia remain largely unknown. To identify potential diagnostic, therapeutic and predictive markers for HA stress, it is important to comprehensively compare and analyse these studies. Towards this goal, HighAltitudeOmicsDB is a unique resource that provides a comprehensive, curated, user-friendly and detailed compilation of various genes/proteins which have been experimentally validated to be associated with various HA conditions, their protein–protein interactions (PPIs) and gene ontology (GO) semantic similarities. For each database entry, HighAltitudeOmicsDB additionally stores the level of regulation (up/down-regulation), fold change, study control group, duration and altitude of exposure, tissue of expression, source organism, level of hypoxia, method of experimental validation, place/country of study, ethnicity, geographical location etc. The database also collates information on disease and drug association, tissue-specific expression level, GO and KEGG pathway associations. The web resource is a unique server platform that offers interactive PPI networks and GO semantic similarity matrices among the interactors.These unique features help to offer mechanistic insights into the disease pathology. Hence, HighAltitudeOmicsDBis a unique platform for researchers working in this area to explore, fetch, compare and analyse HA-associated genes/proteins, their PPI networks, and GO semantic similarities. The database is available at http://www.altitudeomicsdb.in .

Human Acclimatization and therapeutic approaches are the core components for conquering the physiological variations at high altitude (≥2500 m) exposure. The declined atmospheric pressure and reduced partial pressure of oxygen at high altitudes tend to decrease the temperature by several folds. Hypobaric hypoxia is a major threat to humanity at high altitudes, and its potential effects include altitude mountain sickness. On severity, it may lead to the development of conditions like high-altitude cerebral edema (HACE) or high-altitude pulmonary edema (HAPE) and cause unexpected physiological changes in the healthy population of travelers, athletes, soldiers, and low landers while sojourning at high altitude. Previous investigations have been done on long-drawn-out acclimatization strategies such as the staging method to prevent the damage caused by high-altitude hypobaric Hypoxia. Inherent Limitations of this strategy hamper the daily lifestyle and time consuming for people. It is not suitable for the rapid mobilization of people at high altitudes. There is a need to recalibrate acclimatization strategies for improving health protection and adapting to the environmental variations at high altitudes. This narrative review details the geographical changes and physiological changes at high altitudes and presents a framework of acclimatization, pre-acclimatization, and pharmacological aspects of high-altitude survival to enhance the government efficacy and capacity for the strategic planning of acclimatization, use of therapeutics, and safe de-induction from high altitude for minimizing the life loss. It's simply too ambitious for the importance of the present review to reduce life loss, and it can be proved as the most essential aspect of the preparatory phase of high-altitude acclimatization in plateau regions without hampering the daily lifestyle. The application of pre-acclimatization techniques can be a boon for people serving at high altitudes, and it can be a short bridge for the rapid translocation of people at high altitudes by minimizing the acclimatization time.

High-altitude illnesses (HAIs) result from acute exposure to high altitude/hypoxia. Numerous molecular mechanisms affect appropriate acclimatization to hypobaric and/or normobaric hypoxia and curtail the development of HAIs. The understanding of these mechanisms is essential to optimize hypoxic acclimatization for efficient prophylaxis and treatment of HAIs. This review aims to link outcomes of molecular mechanisms to either adverse effects of acute high-altitude/hypoxia exposure or the developing tolerance with acclimatization. After summarizing systemic physiological responses to acute high-altitude exposure, the associated acclimatization, and the epidemiology and pathophysiology of various HAIs, the article focuses on molecular adjustments and maladjustments during acute exposure and acclimatization to high altitude/hypoxia. Pivotal modifying mechanisms include molecular responses orchestrated by transcription factors, most notably hypoxia inducible factors, and reciprocal effects on mitochondrial functions and REDOX homeostasis. In addition, discussed are genetic factors and the resultant proteomic profiles determining these hypoxia-modifying mechanisms culminating in successful high-altitude acclimatization. Lastly, the article discusses practical considerations related to the molecular aspects of acclimatization and altitude training strategies.

Cryptocurrencies are digital currencies void of any support from regulatory body that is currently in vogue as a medium of exchange and an investment security. This paper examines the accounting treatment for cryptocurrency from the perspective of IFRS and AAOIFI accounting standards and propose actions to standard setters on the best way to treat the Crypto transactions in accounting reports. A proper accounting treatment will allow for a fair reporting of crypto related transactions and facilitate users of financial statements to make objective assessment of this new invention. A content analysis was conducted to review all major accounting standards issued by accounting standards setting bodies for possible accounting treatment for cryptocurrencies. To better understand the issue in practice, an analysis of accounting treatment of cryptocurrencies by 2 companies also was conducted. This study found that there is no suitable accounting standard that could objectively be applied for cryptocurrencies. For example, from the perspective of the current accounting standards, cryptocurrencies match the definition of inventory if it is used as a commodity for broker-trader and intangible asset for others respectively. It is suggested that there an urgent need for the International Accounting Standards Board (IASB) to comprehensively develop accounting standard for cryptocurrency, specifically to develop a specific category for this type of assets to allow a standard treatment for cryptocurrency and fill the gap in the IFRS. [ABSTRACT FROM AUTHOR]

Aquaporins, also known as water channels, are a large family of transmembrane channel proteins present throughout all life domains and are implicated in human disorders. The psychrophilic aquaporin comes to attention because of its specialty in adaptive ability to keep on functioning to maintain water homeostasis under low temperatures, which have an optimal temperature for growth at about 15°C or lower. However, studies regarding aquaporin isolated from psychrophilic Pseudomonas sp. are still scattered. Recently, the genome sequence of an Antarctic Pseudomonas sp. strain AMS3 revealed a gene sequence encoding for a putative aquaporin designated as PAqpZ2_AMS3. In this study, structure analysis and molecular dynamics (MD) simulation of a predicted model of a fully hydrated aquaporin monomer was embedded in a lipid bilayer and was performed at different temperatures for structural flexibility and stability analysis. The MD simulation results revealed that the predicted structure could remain stable and flexible at low to medium temperatures. In addition, the important position of water gating amino acids, Phe36 and Asn180 residues were rearranged in -5°C MD simulation, leading to changes in the aquaporin water column size. The information obtained from this psychrophilic aquaporin, PAqpZ2_AMS3, provides new insights into the structural adaptation of this protein at low temperatures and could be a useful tool for low-temperature industrial applications and molecular engineering purposes in the future. [ABSTRACT FROM AUTHOR]

Abstract Background In this study we compare results obtained when applying the monozygotic twin difference cross‐lagged panel model (MZD‐CLPM) and a random intercept cross‐lagged panel model (RI‐CLPM) to the same data. Each of these models is designed to strengthen researchers' ability to draw causal inference from cross‐lagged associations. We explore differences and similarities in how each model does this, and in the results each model produces. Specifically, we examine associations between maladaptive parenting and child emotional and behavioural problems in identical twins aged 9, 12 and 16. Method Child reports of 5698 identical twins from the Twins Early Development Study (TEDS) were analysed. We ran a regular CLPM to anchor our findings within the current literature, then applied the MZD‐CLPM and the RI‐CLPM. Results The RI‐CLPM and MZD‐CLPM each enable researchers to evaluate the direction of effects between correlated variables, after accounting for unmeasured sources of potential confounding. Our interpretation of these models therefore focusses primarily on the magnitude and significance of cross‐lagged associations. In both the MZD‐CLPM and the RI‐CLPM behavioural problems at age 9 resulted in higher levels of maladaptive parenting at age 12. Other effects were not consistently significant across the two models, although the majority of estimates pointed in the same direction. Conclusion In light of the triangulated methods, differences in the results obtained using the MZD‐CLPM and the RI‐CLPM underline the importance of careful consideration of what sources of unmeasured confounding different models control for and that nuance is required when interpreting findings using such models. We provide an overview of what the CLPM, RI‐CLPM and MZD‐CLPM can and cannot control for in this respect and the conclusions that can be drawn from each model.

Abstract The Twins Early Development Study (TEDS) is a longitudinal study following a cohort of twins born 1994–1996 in England and Wales. Of the 13,759 families who originally consented to take part, over 10,000 families remain enrolled in the study. The current focus of TEDS is on mental health in the mid‐twenties. Making use of over 25 years of genetically sensitive data, TEDS is uniquely placed to explore the longitudinal genetic and environmental influences on common mental health disorders in early adulthood. This paper outlines recent data collection efforts supporting this work, including a cohort‐wide mental health assessment at age 26 and a multi‐phase Covid‐19 study. It will also provide an update on data linkage efforts and the Children of TEDS (CoTEDS) project.

This research examines the transition from Scratch to Java programming, highlighting high achievement among participants. The study includes 70 students and utilizes mixed methods, combining quantitative analysis and qualitative narratives. Findings demonstrate the effectiveness of Scratch Visual Teaching Aids (VTA) in developing educational games, understanding algorithm concepts, and improving programming projects. Students' attitudes towards Scratch VTA show increased interest, concentration, and enjoyment in learning. Quantitative analysis indicates positive tool capabilities (mean scores ranging from 3.25 to 3.46). Qualitative narratives reveal varying perceptions of the transition, with prior programming knowledge influencing the shift. Challenges include adapting to the learning session and mastering Java's syntax and concepts. This study enhances programming education practices, providing recommendations for educators during the Scratch-to-Java transition.