Association between iron metabolism and SARS-COV-2 infection, determined by ferritin, hephaestin and hypoxia-induced factor-1 alpha levels in COVID-19 patients.

BACKGROUND: Due to the growing evidence of the importance of iron status in immune responses, the biomarkers of iron metabolism are of interest in novel Coronavirus Disease 2019 (COVID-19). The present prospective study was carried out to compare iron status indicated by levels of ferritin with the levels of two novel biomarkers related to iron homeostasis, hephaestin and hypoxia-inducible factors-1 (HIF-1α) in the serum of patients with COVID-19 in comparison with a control group. METHODS AND RESULTS: Blood samples from 34 COVID-19 patients and from 43 healthy volunteers were collected and the levels of HEPH and HIF-1α were measured by ELISA and compared with levels of serum ferritin. COVID-19 patients had higher serum levels of ferritin than those levels in control group (P < 0.0001). Conversely levels of HIF-1α and HEPH in the COVID-19 group were significantly lower than those of control group (P < 0.0001 for both). An inverse correlation between hephaestin and ferritin as well as between HIF-1α and ferritin was found among all subjects (P < 0.0001), and among COVID-19 patients, but not to statistical significance. CONCLUSION: Levels of hephaestin and HIF-1α were found to be inversely related levels of ferritin across all participants in the study, and to our knowledge this is the first report of hephaestin and HIF-1α as potential markers of iron status. Further studies are needed to corroborate the findings, utilizing a broader range of markers to monitor inflammatory as well as iron status.

Glutamine-Driven Metabolic Adaptation to COVID-19 Infection.

Background: COVID-19 is known to be transmitted by direct contact, droplets or feces/orally. There are many factors which determines the clinical progression of the disease. Aminoacid disturbance in viral disease is shown in many studies. In this study we aimed to evaluate the change of aminoacid metabolism especially the aspartate, glutamine and glycine levels which have been associated with an immune defence effect in viral disease. Methods: Blood samples from 35 volunteer patients with COVID-19, concretized diagnosis was made by oropharyngeal from nazofaringeal swab specimens and reverse transcriptase-polymerase chain reaction, and 35 control group were analyzed. The amino acid levels were measured with liquid chromatography-mass spectrometry technology. Two groups were compared by Kolmogorov-Smirnov analysis, Kruskal-Wallis and the Mann-Whitney U. The square test was used to evaluate the tests obtained by counting, and the error level was taken as 0.05. Results: The average age of the patient and control group were 48.5 ± 14.9 and 48.8 ± 14.6 years respectively. The decrease in aspartate (p = 5.5 × 10-9) and glutamine levels (p = 9.0 × 10-17) were significiantly in COVID group, whereas Glycine (p = 0.243) increase was not significiant. Conclusions: Metabolic pathways, are affected in rapidly dividing cells in viral diseases which are important for immun defence. We determined that aspartate, glutamine and glycine levels in Covid 19 patients were affected by the warburg effect, malate aspartate shuttle, glutaminolysis and pentose phosphate pathway. Enteral or parenteral administration of these plasma amino acid levels will correct the duration and pathophysiology of the patients' stay in hospital and intensive care.

Association of the IL-6R gene polymorphic variant rs2228145(C>A) with IL-6 gene polymorphisms in a healthy cohort of Turkish population.

The main aim of this study was to investigate the relationship of the carriership of rs2228145 allelic variations of IL-6R with two other allelic variations in IL-6 gene at rs1800795 and rs1800796 loci and with the laboratory data of a healthy cohort of the Turkish population. The data of 121 healthy Turkish subjects (aged 12-84 years) including the past diseases, comorbidities were collected. The laboratory parameters were compared by the frequency of alleles of rs2228145 (C>A). The possible association of polymorphism at rs2228145 locus with the age, gender, and body mass index (BMI) and the frequencies of alleles of rs1800795 and rs1800796 polymorphisms were evaluated. The majority of the subjects had allele A at rs2228145 locus and allele G at rs1800796 locus. The number of white blood cells, platelets, neutrophils and monocytes were significantly higher in the subjects with allele C than those with allele A at rs2228145 locus (P < 0.05). The concentrations of total and direct bilirubin, iron, Sex Hormone Binding Globulin (SHBG) and folic acid of the subjects with allele C were significantly lower than those with allele A (P < 0.05). The uric acid and fasting insulin levels were higher in the subjects with allele C compared with those allele A (P = 0.04). The diversities of the hematological parameters, laboratory findings of liver function tests and renal panel and hormone levels may be explained by the variants of rs2228145 locus at IL-6R gene among healthy Turkish individuals.

Vitamin-D Binding Protein Gene Polymorphisms and Serum 25-Hydroxyvitamin-D in a Turkish Population.

The rs7041 and rs4588 polymorphisms found in the GC gene, encoding vitamin D-binding protein (DBP), have distinct biochemical phenotypes. The aim of this study was to investigate vitamin D parameters with these polymorphisms, in individuals with possible vitamin D deficiency. The most common (49% of the cohort) genotype in rs7041 was GT, especially among individuals with high levels of free 25(OH)D calculated but with low levels of bioavailable 25(OH)D, and in rs4588 it was AC in particular among the individuals with low levels of bioavailable 25(OH)D. The most common phenotypes were Gc1s/2 (35.3%) and Gc1s/1s (31.4%), and Gc1f/1f was rare (5.9%). The variations in free and bioavailable 25(OH)D levels among healthy Turkish individuals may be attributed to the variations in total 25(OH)D as well as GC gene polymorphisms. The Turkish population shares a similarity for allele frequencies of rs7041 with the European population and similarity for allele frequencies of rs4588 with Gujarati Indians, and this may also be important in relation to certain ethnic populations showing associations between vitamin D and COVID-19.

Thanatechnology and the Living Dead: New Concepts in Digital Transformation and Human-Computer Interaction.

In a digital society, shall we be the authors of our own experience, not only during our lifetime but also after we die? We ask this question because dying and bereavement have become even harder, and much less private, in the digital age. New big data-driven digital industries and technologies are on the rise, with promises of interactive 3D avatars and storage of digital memories of the deceased, so they can continue to exist online as the "living dead" in a digital afterlife. Famous rock and roll icons like Roy Orbison, Frank Zappa, Ronnie James Dio, and Amy Winehouse have famously been turned into holograms that can once again give "live" performances on the touring circuit, often pulling in large audiences. Death studies, dying, and grief have become virtual in the 21st century. We live in truly unprecedented times for human-computer interactions. Thanatology is the scientific study of death, dying, loss, and grief. In contrast to the biological study of biological aging (cellular senescence) and programmed cell death (apoptosis), thanatology employs multiple professional lenses, medical, psychological, physical, spiritual, ethical, descriptive, and normative. In 1997, Carla Sofka introduced the term thanatechnology as "technological mechanisms such as interactive videodiscs and computer programs that are used to access information or aid in learning about thanatology topics." Onward to 2021, the advent of social media, the Internet of Things, and sensors that digitize and archive nearly every human movement and experience are taking thanatechnology, and by extension, digital transformation, to new heights. For example, what happens to digital remains of persons once they cease to exist physically? This article offers a critical study and snapshot of this nascent field, and the "un-disciplinary" sociotechnical issues digital thanatechnologies raise in relation to big data. We also discuss how best to critically govern this new frontier in systems science and the digital society. We suggest that new policy narratives such as (1) the right to nonparticipation in relation to information and communication technologies and (2) the planetary public goods deserve further attention to democratize thanatechnology and big data. To the extent that systems science often depends on data from online platforms, for example, in times of pandemics and ecological crises, "critical thanatechnology studies," introduced in this article, is a timely and essential field of scholarship with broad importance for systems science and planetary health.

Correlation between interleukin gene polymorphisms and current prevalence and mortality rates due to novel coronavirus disease 2019 (COVID-2019) in 23 countries.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) infection may rely on a potential genetic background for the variations in the inflammatory response. We aimed to investigate the possible correlation between polymorphisms in the IL-6 gene at rs1800796/rs1800795, in IL-6R at rs2228145, in IL-10 at rs1800896 and rs1800871, in IL-17 at rs2275913 and rs763780 loci, and COVID-19 prevalence and mortality rates among populations of 23 countries. METHODS: We searched the literature for polymorphisms in China, Japan, India, Spain, Mexico, Sweden, Turkey, Brazil, Russia, Poland, Italy, South Africa, Netherlands, Greece, Germany, UK, Iran, Finland, Czechia, Tunisia, Norway, Egypt, Croatia. We recorded the prevalence and mortality rates (per million) caused by the Coronavirus infection recorded on 7th September 2020 and 6th December 2020. RESULTS: There was a significant positive correlation between the frequency of AG genotype of rs1800896 and prevalence recorded on 6th December 2020 (r: 0.53, r2 : 0.28, p < .05). There was a significant negative correlation between the mortality rates recorded on 7th September, and the AG genotype of rs2275913 (r: -0.51, r2 : 0.26, p < .05). There was a significant positive correlation between the prevalence recorded on 6th December, and TT genotype at rs763780 (r: 0.65, r2 :0.42, p < .05) while a negative correlation between prevalence and TC genotype at rs763780 (r: -0.66, r2 : 0.43, p < .05). Also, a significant negative correlation was found between mortality rates recorded on 6th December 2020 and CC genotype at rs763780 (r: -0.56, r2 : 0.31, p < .05). CONCLUSION: The variations in prevalence of COVID-19 and its mortality rates among countries may be explained by the polymorphisms at rs1800896 in IL-10, rs2275913 in IL-17A, and rs763780 loci in the IL-17F gene.

The role of DBP gene polymorphisms in the prevalence of new coronavirus disease 2019 infection and mortality rate.

Since December 2019, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, has given rise to emerging respiratory infections with pandemic diffusion. The vitamin D binding protein (DBP) with emphasis on its regulation of total and free vitamin D metabolite levels participate in various clinical conditions. The main goal of this study was to evaluate if there was any association between the DBP gene polymorphism at rs7041 and rs4588 loci and the prevalence of COVID-19 and its mortality rates caused among populations of 10 countries including Turkey. Positive significant correlations were found between the prevalence (per million) and mortality rates (per million), and GT genotype (P < .05) while there was a negative significant correlation between prevalence (per million) and mortality rates (per million), and TT genotype at rs7041 locus among all populations (P < .05). However, no significant correlation was found at rs4588 locus. GT genotype was found to confer this susceptibility to the populations of Germany, Mexico, Italy, Czech, and Turkey. The variations in the prevalence of COVID-19 and its mortality rates among countries may be explained by Vitamin D metabolism differed by the DBP polymorphisms of rs7041 and rs4588.

Glutamine depletion in patients with Crimean-Congo hemorrhagic fever.

Crimean-Congo hemorrhagic fever (CCHF) is a viral disease. There is not enough knowledge about plasma amino acid levels in CCHF. Therefore, we investigated plasma amino acid levels in patients with CCHF and the association between the levels of these amino acids and disease severity. The plasma amino acid levels (including glutamate [Glu], aspartate [Asp], glutamine [Gln], asparagine [Asn] and gamma-aminobutyric acid [GABA]) in CCHF patients and controls were measured by using liquid chromatography-mass spectrometry. Plasma levels of Gln were lower while Asp, Glu, and GABA levels were higher in patients. In fatal CCHF patients, we found the plasma level of Asn was increased whereas the plasma level of GABA was decreased. This study is the first in the literature to evaluate the plasma Gln, Glu, Asn, Asp, and GABA levels in CCHF patients. We found that the plasma Gln levels were significantly lower in CCHF patients while Asp, Glu, and GABA levels were elevated. Considering that these amino acids are important for immune cells, the plasma amino acid levels of CCHF patients may contribute to the understanding of the pathophysiology of disease and it can be important for supportive treatment of CCHF.

Digging Deeper into Precision/Personalized Medicine: Cracking the Sugar Code, the Third Alphabet of Life, and Sociomateriality of the Cell.

Precision/personalized medicine is a hot topic in health care. Often presented with the motto "the right drug, for the right patient, at the right dose, and the right time," precision medicine is a theory for rational therapeutics as well as practice to individualize health interventions (e.g., drugs, food, vaccines, medical devices, and exercise programs) using biomarkers. Yet, an alien visitor to planet Earth reading the contemporary textbooks on diagnostics might think precision medicine requires only two biomolecules omnipresent in the literature: nucleic acids (e.g., DNA) and proteins, known as the first and second alphabet of biology, respectively. However, the precision/personalized medicine community has tended to underappreciate the third alphabet of life, the "sugar code" (i.e., the information stored in glycans, glycoproteins, and glycolipids). This article brings together experts in precision/personalized medicine science, pharmacoglycomics, emerging technology governance, cultural studies, contemporary art, and responsible innovation to critically comment on the sociomateriality of the three alphabets of life together. First, the current transformation of targeted therapies with personalized glycomedicine and glycan biomarkers is examined. Next, we discuss the reasons as to why unraveling of the sugar code might have lagged behind the DNA and protein codes. While social scientists have historically noted the importance of constructivism (e.g., how people interpret technology and build their values, hopes, and expectations into emerging technologies), life scientists relied on the material properties of technologies in explaining why some innovations emerge rapidly and are more popular than others. The concept of sociomateriality integrates these two explanations by highlighting the inherent entanglement of the social and the material contributions to knowledge and what is presented to us as reality from everyday laboratory life. Hence, we present a hypothesis based on a sociomaterial conceptual lens: because materiality and synthesis of glycans are not directly driven by a template, and thus more complex and open ended than sequencing of a finite length genome, social construction of expectations from unraveling of the sugar code versus the DNA code might have evolved differently, as being future-uncertain versus future-proof, respectively, thus potentially explaining the "sugar lag" in precision/personalized medicine diagnostics over the past decades. We conclude by introducing systems scientists, physicians, and biotechnology industry to the concept, practice, and value of responsible innovation, while glycomedicine and other emerging biomarker technologies (e.g., metagenomics and pharmacomicrobiomics) transition to applications in health care, ecology, pharmaceutical/diagnostic industries, agriculture, food, and bioengineering, among others.

Birth of Industry 5.0: Making Sense of Big Data with Artificial Intelligence, "The Internet of Things" and Next-Generation Technology Policy.

Driverless cars with artificial intelligence (AI) and automated supermarkets run by collaborative robots (cobots) working without human supervision have sparked off new debates: what will be the impacts of extreme automation, turbocharged by the Internet of Things (IoT), AI, and the Industry 4.0, on Big Data and omics implementation science? The IoT builds on (1) broadband wireless internet connectivity, (2) miniaturized sensors embedded in animate and inanimate objects ranging from the house cat to the milk carton in your smart fridge, and (3) AI and cobots making sense of Big Data collected by sensors. Industry 4.0 is a high-tech strategy for manufacturing automation that employs the IoT, thus creating the Smart Factory. Extreme automation until "everything is connected to everything else" poses, however, vulnerabilities that have been little considered to date. First, highly integrated systems are vulnerable to systemic risks such as total network collapse in the event of failure of one of its parts, for example, by hacking or Internet viruses that can fully invade integrated systems. Second, extreme connectivity creates new social and political power structures. If left unchecked, they might lead to authoritarian governance by one person in total control of network power, directly or through her/his connected surrogates. We propose Industry 5.0 that can democratize knowledge coproduction from Big Data, building on the new concept of symmetrical innovation. Industry 5.0 utilizes IoT, but differs from predecessor automation systems by having three-dimensional (3D) symmetry in innovation ecosystem design: (1) a built-in safe exit strategy in case of demise of hyperconnected entrenched digital knowledge networks. Importantly, such safe exists are orthogonal-in that they allow "digital detox" by employing pathways unrelated/unaffected by automated networks, for example, electronic patient records versus material/article trails on vital medical information; (2) equal emphasis on both acceleration and deceleration of innovation if diminishing returns become apparent; and (3) next generation social science and humanities (SSH) research for global governance of emerging technologies: "Post-ELSI Technology Evaluation Research" (PETER). Importantly, PETER considers the technology opportunity costs, ethics, ethics-of-ethics, framings (epistemology), independence, and reflexivity of SSH research in technology policymaking. Industry 5.0 is poised to harness extreme automation and Big Data with safety, innovative technology policy, and responsible implementation science, enabled by 3D symmetry in innovation ecosystem design.

Stop the Spam! Conference Ethics and Decoding the Subtext in Post-Truth Science. What Would Denis Diderot Say?

Science and its practice always had a subtext, subject to influence by scientists', funders', and other innovation actors' values and assumptions. The recent emergence of post-truth, authoritarian and populist penchants, in both developed and developing countries, has further blurred the already fluid boundaries between material scientific facts and their social construction/shaping by scientific subtext, human values, powers, and hegemony. While there are certain checks, balances, and oversight mechanisms for publication ethics, other pillars of science communication, most notably, scientific conferences and their governance, are ill prepared for post-truth science. Worrisomely, the proliferation of spam conferences is a major cause for concern for integrative biology and postgenomic science. The current gaps in conference ethics are important beyond science communication because conferences help build legitimacy of emerging technologies and frontiers of science and, thus, bestows upon the organizers, funders, enlisted scientific advisors, speakers, among others, power, which in turn needs to be checked. Denis Diderot (1713-1784), a prominent intellectual during the Enlightenment period, has aptly observed that the very act of organizing brings about power, influence, and control. If the subtext of conference practices is left unchecked, it can pave the way for hegemony, and yet more volatile and violent authoritarian governance systems in science and society. This begs for innovative solutions to increase accountability, resilience, and capacity of technology experts and scientists to discern and decode the subtext in science and its communication in the current post-truth world. We propose that the existing undergraduate and graduate programs in life and physical sciences and medicine could be redesigned to include a rotation for exposure to and training in political science. Such innovative PhD+ programs straddling technical and political science scholarship would best equip future students and citizens to grasp and respond to subtext and embedded opaque value and power systems in scientific practices in an increasingly post-truth world. Political science scholarship unpacks the inner workings, subtext, and power dynamics in science and society. Thus, knowledge of political science competency is akin to molecular biology in life sciences. Both make the invisible (e.g., cell biology versus subtext of knowledge) visible. The ability to read subtext in science and claims of post-truth knowledge is a new and essential form of societal literacy in 21st century science and integrative biology.

G-quadruplex prediction in E. coli genome reveals a conserved putative G-quadruplex-Hairpin-Duplex switch.

Many studies show that short non-coding sequences are widely conserved among regulatory elements. More and more conserved sequences are being discovered since the development of next generation sequencing technology. A common approach to identify conserved sequences with regulatory roles relies on topological changes such as hairpin formation at the DNA or RNA level. G-quadruplexes, non-canonical nucleic acid topologies with little established biological roles, are increasingly considered for conserved regulatory element discovery. Since the tertiary structure of G-quadruplexes is strongly dependent on the loop sequence which is disregarded by the generally accepted algorithm, we hypothesized that G-quadruplexes with similar topology and, indirectly, similar interaction patterns, can be determined using phylogenetic clustering based on differences in the loop sequences. Phylogenetic analysis of 52 G-quadruplex forming sequences in the Escherichia coli genome revealed two conserved G-quadruplex motifs with a potential regulatory role. Further analysis revealed that both motifs tend to form hairpins and G quadruplexes, as supported by circular dichroism studies. The phylogenetic analysis as described in this work can greatly improve the discovery of functional G-quadruplex structures and may explain unknown regulatory patterns.

An Appeal to the Global Health Community for a Tripartite Innovation: An "Essential Diagnostics List," "Health in All Policies," and "See-Through 21(st) Century Science and Ethics".

Diagnostics spanning a wide range of new biotechnologies, including proteomics, metabolomics, and nanotechnology, are emerging as companion tests to innovative medicines. In this Opinion, we present the rationale for promulgating an "Essential Diagnostics List." Additionally, we explain the ways in which adopting a vision for "Health in All Policies" could link essential diagnostics with robust and timely societal outcomes such as sustainable development, human rights, gender parity, and alleviation of poverty. We do so in three ways. First, we propose the need for a new, "see through" taxonomy for knowledge-based innovation as we transition from the material industries (e.g., textiles, plastic, cement, glass) dominant in the 20(th) century to the anticipated knowledge industry of the 21st century. If knowledge is the currency of the present century, then it is sensible to adopt an approach that thoroughly examines scientific knowledge, starting with the production aims, methods, quality, distribution, access, and the ends it purports to serve. Second, we explain that this knowledge trajectory focus on innovation is crucial and applicable across all sectors, including public, private, or public-private partnerships, as it underscores the fact that scientific knowledge is a co-product of technology, human values, and social systems. By making the value systems embedded in scientific design and knowledge co-production transparent, we all stand to benefit from sustainable and transparent science. Third, we appeal to the global health community to consider the necessary qualities of good governance for 21st century organizations that will embark on developing essential diagnostics. These have importance not only for science and knowledge-based innovation, but also for the ways in which we can build open, healthy, and peaceful civil societies today and for future generations.