Calcium/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) regulates bone remodeling through its effects on osteoblasts and osteoclasts. However, its role in osteocytes, the most abundant bone cell type, and the master regulator of bone remodeling, remains unknown. Here we report that the conditional deletion of CaMKK2 from osteocytes using Dentine matrix protein 1 (Dmp1)-8kb-Cre mice led to enhanced bone mass only in female mice owing to a suppression of osteoclasts. Conditioned media isolated from female CaMKK2-deficient osteocytes inhibited osteoclast formation and function in in vitro assays, indicating a role for osteocyte-secreted factors. Proteomics analysis revealed significantly higher levels of extracellular calpastatin, a specific inhibitor of calcium-dependent cysteine proteases calpains, in female CaMKK2 null osteocyte conditioned media, compared to media from female control osteocytes. Further, exogenously added non-cell permeable recombinant calpastatin domain I elicited a marked, dose-dependent inhibition of female wild-type osteoclasts and depletion of calpastatin from female CaMKK2-deficient osteocyte conditioned media reversed the inhibition of matrix resorption by osteoclasts. Our findings reveal a novel role for extracellular calpastatin in regulating female osteoclast function and unravel a novel CaMKK2-mediated paracrine mechanism of osteoclast regulation by female osteocytes.

Recent lines of evidence suggest the intriguing hypothesis that consuming common culinary herbs of the mint family might help prevent or treat Covid. Individual citizens could easily explore the hypothesis using ordinary kitchen materials. I offer a philosophical framework to account for the puzzling lack of public health messaging about this interesting idea.

Nasal cavity is a primary checkpoint for the invasion of several respiratory pathogens. Numerous pathogens including SARS-CoV-2, S. pneumonia, S. aureus, etc., adhere to the nasal epithelium or mucus to invade and trigger an infection. IgA serves as the first line of defense against foreign antigens and pathogens. They exhibit cross-reactivity against a diverse variety of antigens through immune exclusion, which intercepts the invasion of pathogens through the mucosal lining. Advances in intranasal immunization technology underscore the elevated neutralizing IgA levels at local and distal mucosa in contrast to the parenteral vaccines. This review highlights the adjuvants that induce IgA class switching and the challenges of maintaining nominal IgA levels at the mucosal surface. Finally, the review features the paradigm-shifting of conventional immunization techniques to IgA-inducing vaccines to enhance protection against homologous and heterologous pathogens.

A 2-year prospective study carried out on ventilator-associated pneumonia (VAP) patients in the intensive care unit at King Khalid hospital, Hail, Kingdom of Saudi Arabia (KSA), revealed a high prevalence of extremely drug-resistant (XDR) Acinetobacter baumannii. About a 9% increase in the incidence rate of A. baumannii has occurred in the VAP patients between 2019 and 2020 (21.4% to 30.7%). In 2019 the isolates were positive for IMP-1 and VIM-2 (31.1% and 25.7%, respectively) as detected by PCR. In comparison, a higher proportion of isolates produced NDM-1 in 2020. Here, we observed a high resistant proportion of ICU isolates towards the most common antibiotics in use. Colistin sensitivity dropped to 91.4% in the year 2020 as compared to 2019 (100%). Thus, the finding of this study has a highly significant clinical implementation in the clinical management strategies for VAP patients. Furthermore, strict implementation of antibiotic stewardship policies, regular surveillance programs for antimicrobial resistance monitoring, and screening for genes encoding drug resistance phenotypes have become imperative.

Dengue is a viral mosquito-borne disease that rapidly spreads in tropical and subtropical countries, including the Philippines. One of its most distinguishing characteristics is the ability of the Dengue Virus (DENV) to easily surpass the innate responses of the body, thus activating B cells of the adaptive immunity to produce virus-specific antibodies. Moreover, Dengvaxia® is the only licensed vaccine for DENV, but recent studies showed that seronegative individuals become prone to increased disease severity and hospitalization. Owing to this limitation of the dengue vaccine, this study determined and compared consensus and unique B cell epitopes among each DENV (1-4) Philippine isolate to identify potential areas of interest for future vaccine studies and therapeutic developments. An in silico-based epitope prediction of forty (40) DENV 1-4 strains, each serotype represented by ten (10) sequences from The National Center for Biotechnology Information (NCBI), was conducted using Kolaskar and Tongaonkar antigenicity, Emini surface accessibility, and Parker hydrophilicity prediction in Immune Epitope Database (IEDB). Results showed that five (5) epitopes were consensus for DENV-1 with no detected unique epitope, one (1) consensus epitope for DENV-2 with two (2) unique epitopes, one (1) consensus epitope for DENV-3 plus two (2) unique epitopes, and two (2) consensus epitopes and one (1) unique epitope for DENV-4. The findings of this study would contribute to determining potential vaccine and diagnostic marker candidates for further research studies and immunological applications against DENV (1-4) Philippine isolates.

Adipose tissue (AT) is a remarkably plastic and active organ with functional pleiot-ropism and high remodeling capacity. Although the expansion of fat mass, by defini-tion, represents the hallmark of obesity, the dysregulation of the adipose organ emerges as the forefront of the link between adiposity and its associated metabolic and cardio-vascular complications. The dysfunctional fat displays distinct biological signatures, which include enlarged fat cells (i.e., adipocyte hypertrophy), low-grade inflammation, impaired redox homeostasis, and cellular senescence. While these events are orches-trated in a cell-type, context-dependent and temporal manner, the failure of the adipose precursor cells to form new mature adipocytes appears the main instigator of the adi-pose dysregulation, which, ultimately, poses a deleterious milieu either by promoting ectopic lipid overspill in non-adipose targets (i.e., lipotoxicity) or by inducing an al-tered secretion of different adipose-derived hormones (i.e., adipokines and lipokines). This novel paradigm (“expandability hypothesis”) challenges and extends previous “adipocentric view”, which implies a reduced plasticity of the adipose organ at the nexus between “unhealthy” fat expansion and the development of obesity-associated comorbidities. In this review, we will briefly summarize the potential mechanisms by which adaptive changes to variations of energy balance may impair adipose plasticity and promote fat organ dysfunction. We will also highlight the conundrum with the perturbation of the adipose microenvironment and the development of cardio-metabolic complications by focusing on adipose lipoxidation and cellular senescence. Finally, we discuss the sci-entific rationale for proposing adipose organ plasticity as a target to curb/prevent adi-posity-linked cardio-metabolic complications.

The emergence of the COVID-19 pandemics prompted a fast development of novel diagnostic methods of the etiologic virus SARS-CoV-2. Methods based on CRISPR-Cas systems have been particularly promising because they can achieve a similar sensitivity and specificity to the golden standard RT-qPCR, especially when coupled to an isothermal pre-amplification step. Furthermore, they have also solved inherent limitations of RT-qPCR that impede its decentralized use and deployment in the field, such as the need for expensive equipment, high cost per reaction, and delivery of results in hours, among others. In this review, we evaluate publicly available methods to detect SARS-CoV-2 that are based on CRISPR-Cas and isothermal amplification. We critically analyze the steps required to obtain a successful result from clinical samples and pinpoint key experimental conditions and parameters that could be optimized or modified to improve clinical and analytical outputs. The COVID outbreak has propelled intensive research in a short time, which is paving the way to develop effective and very promising CRISPR-Cas systems for the precise detection of SARS-CoV-2. This review could also serve as an introductory guide to new labs delving into this technology.

Background/methods: For mechanistic studies, in vitro human B cell differentiation and generation of plasma cells are invaluable techniques. However, the heterogeneity of both T cell-dependent (TD) and T cell-independent (TI) stimuli and the disparity of culture conditions used in existing protocols makes interpretation of results challenging. The aim of the present study was to achieve the most optimal B cell differentiation conditions using isolated CD19⁺ B cells and PBMC cultures. We addressed multiple seeding densities, different durations of culturing and various combinations of TD stimuli and TI stimuli including B cell receptor (BCR) triggering. B cell expansion, proliferation and differentiation was analyzed after 6 and 9 days by measuring B cell proliferation and expansion, plasmablast and plasma cell formation and immunoglobulin (Ig) secretion. In addition, these conditions were extrapolated using cryopreserved cells and differentiation potential was compared. Results: This study demonstrates improved differentiation efficiency after 9 days of culturing for both B cell and PBMC cultures using CD40L and IL-21 as TD stimuli and 6 days for CpG and IL-2 as TI stimuli. We arrived at optimized protocols requiring 2500 and 25.000 B cells per culture well for TD and TI assays, respectively. The results of the PBMC cultures were highly comparable to the B cell cultures, which allows dismissal of additional B cell isolation steps prior to culturing. In these optimized TD conditions, the addition of anti-BCR showed little effect on phenotypic B cell differentiation, however it interferes with Ig secretion measurements. Addition of IL-4 to the TD stimuli showed significantly lower Ig secretion. The addition of BAFF to optimized TI conditions showed enhanced B cell differentiation and Ig secretion in B cell but not in PBMC cultures. With this approach, efficient B cell differentiation and Ig secretion was accomplished when starting from fresh or cryopreserved samples. Conclusion: Our methodology demonstrates optimized TD and TI stimulation protocols for more indepth analysis of B cell differentiation in primary human B cell and PBMC cultures while requiring low amounts of B cells, making them ideally suited for future clinical and research studies on B cell differentiation of patient samples from different cohorts of B cell-mediated diseases.

The open-bundle structure of cytochrome c’ as an unfolding intermediate was determined by small-angle neutron scattering experiment (SANS). The four-α-helix bundle structure of Cyt c’ at neutral pH was transited to an open-bundle structure (at pD ~13), which is a joint-clubs consisting of four clubs (α-helices) connected by short loops. The compactly folded structure of Cyt c’ (radius of gyration, Rg = 18 Å for the Cyt c’ dimer) at neutral or mildly alkaline pD transitioned to a remarkably larger “open-bundle” structure at pD ~13 (Rg = 25 Å for the Cyt c’ monomer). Cyt c’ adopts an unstructured random coil structure at pD = 1.7 (Rg = 25 Å for the Cyt c’ monomer). Numerical partial scattering function analysis (joint-clubs) and ab initio modelling gave structures similar to the “open-bundle”, which retains the α-helices but loses the bundle structure.

The anisotropy in the CMBR detected by the COBE satellite has sprouted the research and theories of the void that got created, after being washed away by a parallel universe after its collision. This details of the roadmap to the parallel universe, that are previously been entangled, but now, separated, with the concept of 2-time dimensions as a time curve of containing the closed curves embedded on the surface area, thereby time running backward in orientation in the parallel universe, along with the perspective of eternal inflation and divided subspaces giving birth to twin universes are provided here. This time curve being responsible for creating an exponentiality of time frames, growing in layers, giving us the perception of the confabulations being an indication of the previously connected worlds.

Rare earths are classified as most important and critical material for US economy and defense by Congress and a mandate has been set to increase their in-house production, domestic resource utilization and decrease reliance on foreign resources and reserves. They are widely available in earth crust as ore (bastnaesite (La, Ce)FCO₃, monazite, (Ce, La, Y, Th)PO₄, and xenotime, YPO₄), but their so-called economic reserves are sparsely located geographically. They may be produced by various means such as beneficiation (physical, chemical, mechanical, or electrical), reduction (direct or indirect), electrolysis (of aqueous or molten / fused single or mixed salt systems) at high temperature or hydrometallurgy. Out of these, direct reduction also known as metallothermic reduction (La and Ca reduction) is mostly utilized. Its variant, high temperature electrowinning of fused salts is also practiced widely. These processes are material and application specific. In this study, author will employ thermodynamics (Ellingham diagrams, free energy of formation, reduction potential, Nernst equation, Pourbaix (E_h-pH) diagrams, E-pO^-2 diagrams), kinetics and energetic of a chemical reaction (chemical metallurgy) to reduce rare earth oxide / salt to rare earth metals (REO/RES – REM). It is shown that materials and energy requirement vary greatly depending on type of mineral ore, production facility, and beneficiation / mineral processing method selected. Aim is to reduce dependence on coal deposits. It is anticipated this route will be able to produce rare earths with > 35% yield and > 98% purity which be described in subsequent studies and patents.

Identifying the SARS-CoV-2 virus has been a unique challenge for the scientific community. In this paper, we discuss a practical solution to help guide clinicians with interpretation of the probability that a positive, or negative, COVID-19 test result indicates an infected person, based on their clinical estimate of pre-test probability of infection.The authors conducted a small survey on LinkedIn to confirm that hypothesis that that the clinical pre-test probability of COVID-19 increases relative to local prevalence of disease plus patient age, known contact, and severity of symptoms. We examined results of PPA (Positive Percent Agreement, sensitivity) and NPA (Negative Percent Agreement, specificity) from 73 individual laboratory experiments for molecular tests for SARS-CoV-2 as reported to the FIND database ¹, and for selected methods in FDA EUA submissions^2,3. Authors calculated likelihood ratios to convert pre-test to post-test probability of disease and designed an online calculator to create graphics and text to report results. Despite best efforts, false positive and false negative Covid-19 test results are unavoidable^4,5. A positive or negative test result from one laboratory has a different probability for the presence of disease than the same result from another laboratory. Likelihood ratios and confidence intervals can convert the physician or other healthcare professional’s clinical estimate of pre-test probability to post-test probability of disease. Ranges of probabilities differ depending on proven method PPA and NPA in each laboratory. We recommend that laboratories verify PPA and NPA and utilize a the “Clinician’s Probability Calculator” to verify acceptable test performance and create reports to help guide clinicians with estimation of post-test probability of COVID-19.

This research analyzed the impact of quality of service as perceived by Hapkido students on their exercise continuation and recommendation intentions. It also identified the measures to reduce the rate of student dropout, strengthen competitiveness, and create more efficient marketing strategies for consumer patterns that are rapidly diversifying Hapkido. A questionnaire survey method was conducted with 300 middle and high school students aged 14–19 years having Hapkido training of three months to two years in Incheon and Bucheon during March–April 2019. Frequency, factor, reliability, correlation, and standard multiple regression analyses were conducted on the surveyed data. The conclusions are as follows. First, considering the impact of service quality on exercise continuation intention, service quality positively affects reliability, personification, and perceptual openness; in terms of possibility, it positively affects typicality, personification, and perceptual openness; and in terms of reinforcement, it positively affects reliability and perceptual openness. Second, examining the impact of service quality on recommendation intention positively affects reliability, personification, and perceptual openness. Third, exercise continuation intention positively affects recommendation intention.

Utility of vaccine campaigns to control coronavirus disease 2019 (COVID-19) is not merely dependent on vaccine efficacy and safety. Vaccine acceptance among the general public and the healthcare workers, appears to have a decisive role for successful control of the pandemic. The aim of this review was to provide an up-to-date assessment of COVID-19 vaccination acceptance rates worldwide. A systematic search of the peer-reviewed English survey literature indexed in PubMed was done on December 25, 2020. Results from 30 studies, met the inclusion criteria and formed the basis for final COVID-19 vaccine acceptance estimates. Results of an additional recent survey from Jordan and Kuwait was considered in this review as well. Survey studies on COVID-19 vaccine acceptance rates were found from 33 different countries. Among adults representing the general public, the highest COVID-19 vaccine acceptance rates were found in Ecuador (97.0%), Malaysia (94.3%), Indonesia (93.3%) and China (91.3%). On the other hand, the lowest COVID-19 vaccine acceptance rates were found in Kuwait (23.6%), Jordan (28.4%), Italy (53.7), Russia (54.9%), Poland (56.3%), US (56.9%), and France (58.9%). Only eight surveys among healthcare workers (doctors, nurses) were found, with vaccine acceptance rates ranging from 27.7% in the Democratic Republic of the Congo to 78.1% in Israel. In a majority of survey studies among the general public (62%), the acceptance of COVID-19 vaccination showed a level of ≥ 70%. Low rates of COVID-19 vaccine acceptance were reported in the Middle East, Russia, Africa and several European countries. This could represent a major problem in the global efforts that aim to control the current COVID-19 pandemic. More studies are recommended to address the scope of COVID-19 vaccine hesitancy. Such studies are particularly needed in the Middle East Africa, Eastern Europe, Central Asia, Middle and Latin America.

There are limited proven therapies for the treatment of COVID-19. Vitamin C’s antioxidant, anti-inflammatory and immunomodulating effects, make it a potential therapeutic candidate, both for the prevention and amelioration of COVID-19 infection, and as an adjunctive therapy in the critical care of COVID-19, supporting anti-inflammatory treatment. This literature review focuses on vitamin C deficiency in respiratory infections including COVID-19; the mechanism of action in infectious disease and adrenal function supporting the anti-inflammatory actions of glucocorticosteroids: its role in preventing and treating colds and pneumonia and its role in treating sepsis and COVID-19. The evidence to date indicates that oral vitamin C (2-8g/d) may reduce incidence and duration of respiratory infections and intravenous vitamin C (2-24g/d) has been shown to reduce mortality, Intensive Care Unit and hospital stays, time on mechanical ventilation in severe respiratory infections. Further trials are urgently warranted. Given the favourable safety profile and low cost of vitamin C, and frequency of vitamin C deficiency in respiratory infections it may be worthwhile testing patients’ vitamin C status and treating accordingly with intravenous use within ICUs and orally with doses between 2 and 8g/day in hospitalised and infected persons.

Rising child obesity rate creates a need for tools quantifying metabolic changes in obese children and adolescents for purposes of comorbidities early detection or prevention. A candidate for such role seem to be miRNAs – in vivo serving as the suppressing factors of the gene expression. The aim of this study was to review the recent discoveries in this field and to conclude directions of research or application of studied molecules. Repeated browsing of databases, followed by screening for eligibility of results, led to final approval of 9 articles. Filtered studies examined the differences in miRNA (miR) expression levels of obese subjects and children suffering from obesity comorbidities. Studies concerning the endothelial dysfunction (ED) identified miR-630 as a possible treatment option. Search for the alternative markers in diagnosis of non-alcoholic fatty liver disease (NAFLD) suggested value of miR-199a-5p and miR-122. MiR-486, miR-146b and miR-15b may serve as a panel of markers grading the development of type 2 diabetes mellitus (T2DM) in children, although further research raised doubts in that matter. Another panel of miRNA molecules was indicated as useful in early detection of alterations leading to metabolic syndrome (MetS). No valid link between studied miRNAs and atherosclerosis (AS) was found. MiRNAs seem to be promising prognostic markers for the diagnosis of NAFLD, T2DM and MetS in children. Further studies are required to support these findings.

In this paper, we present an extended version of the Hadi-Vencheh model for multiple criteria ABC inventory classification. The proposed model is a nonlinear weighted product model (WPM) which determines a common set of weights for all the items. Our proposed nonlinear WPM incorporates multiple criteria with different measure units, without converting the performance of each inventory item in terms of each criterion into a normalized attribute value, thereby providing an improvement over the model proposed by Hadi-Vencheh. Our study mainly includes various criteria for ABC classification, and demonstrates an efficient algorithm for solving nonlinear programming problems in which the feasible solution set does not have to be convex. The algorithm presented in this study improves the solution efficiency of the Canonical Coordinates Method (CCM) algorithm substantially when applied to large scale, nonlinear programming problems. The modified algorithm was tested to compare our proposed model results to the results derived using the Hadi-Vencheh model and demonstrate the algorithm's efficacy. The practical implications of the study are to develop an efficient nonlinear optimization solver by optimizing the quality of existing solutions, thus improving time and space efficiency.

Purpose: During the COVID-19 pandemic, the health care workers (HCWs) at the frontline have been largely exposed to infected patients, running an high risk of being infected by the SARS-CoV-2 virus. This study investigates the epidemiological, clinical and lifestyles characteristics that might play roles in the susceptibility of HCWs to COVID-19 in a hit Italian hospital. Methods:Demographic, lifestyle, work-related and comorbidities data of 1447 HCWs which underwent a nasopharyngeal swab for SARS-CoV-2 were retrospectively collected. For the 164 HCWs positive for SARS-CoV-2, data about safety in the workplace, symptoms and clinical course of COVID-19 were also collected. Cumulative incidence of SARS-CoV-2 infection was estimated. Risk factors for SARS-CoV-2 infection were assessed using a multivariable Poisson regression. Results: The cumulative incidence of SARS-CoV-2 infection among the screened HCWs was 11.33 (9.72-13.21). Working in a COVID-19 ward, being a former smoker (vs being a person who never smoked) and BMI were positively associated with SARS-CoV-2 infection, whereas being a current smoker was negatively associated with this variable. Conclusions: Assuming an equal accessibility and proper use of PPE of all the HCWs of our Hospital, the great and more prolonged contact with COVID-19 patients remains the crucial risk factor for SARS-CoV-2. Therefore, increased and particular care needs to be focused specifically on the most exposed HCWs groups, which should be safeguarded. Furthermore, in order to limit the risk of asymptomatic spread of SARS-CoV-2 infection, the HCWs mild symptoms of COVID-19 should be considered when evaluating the potential benefits of universal staff testing

Evidence was brought forward in England and the USA that Black, Asian, Latino and Minority Ethnic people exhibit higher mortality risk from COVID-19 than White people. While socioeconomic factors were suggested to contribute to this trend, they arguably do not explain the range of the differences observed, allowing for possible genetic implications. Almost concurrently, the analysis of a cohort in Chinese COVID-19 patients proposed an association between the severity of the disease and the presence of the minor allele of rs12252 of the Interferon-induced transmembrane protein 3 (IFITM3) gene. This SNP, together with rs34481144, are the two most studied polymorphisms of IFITM3 and have been associated in the past with increased severity in Influenza, Dengue, Ebola, and HIV viruses. IFITM3 is an immune effector protein that is pivotal for the restriction of viral replication, but also for the regulation of cytokine production. Following up to these two developments in the ongoing SARS-CoV-2 pandemic, the present study investigates a possible association between the differences in mortality of ethnic groups in England and the combined haplotypes of rs12252 and rs34481144. The respective allele frequencies were collected for 26 populations from 1000 Genomes Project and subgroups were pooled wherever possible to create correspondences with ethnic groups in England. A significant correlation (r=0.9687, p= 0.0003) was observed between the reported Standardized Mortality Ratios and the frequency of the combined haplotype of both reference alleles, suggesting that the combination of reference alleles of the specific SNPs may be implicated in more severe outcomes of COVID-19. This study calls for further focus on the role of IFITM3 variants in the mechanism of cellular invasion of SARS-CoV-2, their impact in COVID-19 severity and their possible implications in vaccination efficacy.

Abstract The COVID-19 pandemic is thought to began in Wuhan, China in December 2019. Mobility analysis identified East-Asia and Oceania countries to be highly-exposed to COVID-19 spread, consistent with the earliest spread occurring in these regions. However, here we show that while a strong positive correlation between case-numbers and exposure level could be seen early-on as expected, at later times the infection-level is found to be negatively correlated with exposure-level. Moreover, the infection level is positively correlated with the population size, which is puzzling since it has not reached the level necessary for population-size to affect infection-level through herd immunity. These issues are resolved if a low-virulence Corona-strain (LVS) began spreading earlier in China outside of Wuhan, and later globally, providing immunity from the later appearing high-virulence strain (HVS). Following its spread into Wuhan, cumulative mutations gave rise to the emergence of an HVS, known as SARS-CoV-2, starting the COVID-19 pandemic. We model the co-infection by an LVS and an HVS, and show that it can explain the evolution of the COVID-19 pandemic and the non-trivial dependence on the exposure level to China and the population-size in each country. We find that the LVS began its spread a few months before the onset of the HVS, and that its spread doubling-time is $\sim 1.59\pm 0.17$ times slower than the HVS. Although more slowly spreading, its earlier onset allowed the LVS to spread globally before the emergence of the HVS. In particular, in countries exposed earlier to the LVS and/or having smaller population-size, the LVS could achieve herd-immunity earlier, and quench the later-spread HVS at earlier stages. We find our two-parameter (the spread-rate and the initial onset time of the LVS) can accurately explain the current infection levels (R^2$\mathrm{=0.74}$; correlation p-value (p) of 5x10^-13$$). Furthermore, countries exposed early should have already achieved herd-immunity. We predict that in those countries cumulative infection levels could rise by no more than 2-3 times the current level through local-outbreaks, even in the absence of any containment measures. We suggest several tests and predictions to further verify the double-strain co-infection model and discuss the implications of identifying the LVS.

A 47-year-old physician suddenly noticed a persistent difficulty maintaining attention. He was awake, alert, and oriented. After two hours he developed fever, ageusia, and anosmia. He denied any previous history of psychiatric illness and was hydrated at the time of the subjective attention impairment. On admission, the patient remained oriented. He reported the persistence of attention problems, anosmia, and mild fatigue. The oxygen saturation 99% while he was breathing ambient air. Laboratory tests were unremarkable. A high-resolution computed tomography of the chest was normal. Nasopharyngeal and throat swabs specimens on reverse transcription-polymerase chain reaction analysis tested positive for SARS-CoV2. On illness day 3, the examination was unchanged, but he continued to complain of difficulties to stay focused. Then, he performed an objective attention test. The test demonstrated a moderate attentional impairment. On day 6, the patient reported a subjective worse in his concentration and performed a second test. Although his physical examination remained normal, the attention performance was worse as compared to day 3. Eight hours after worsening of attention impairment, the patient’s oxygen saturation dropped to 94%. From illness days 9 to 14, the patient evolved with clinical improvement. On day 10, a third objective attention test indicated a mild deficit. On day 16, he did not report any other symptom and the attention test was completely normal. Then, the patient returned to work. Neurological symptoms had been previously described in COVID- 19 patients. However, no previous research had investigated early cognitive deficits preceding the traditional symptoms.

Background: It is unclear why certain countries have been more severely affected by COVID-19 than other countries. Methods: In this ecological study we compared COVID-19 mortality and incidence/100,000 as well as 4 putative explanatory factors by WHO world region. Linear regression was then used to assess the country-level predictors of COVID-19 mortality/100,000 and incidence/100,000 in 204 countries with available data. Results: COVID-19 incidence and mortality/capita were greater in Europe than other regions. This was despite a higher testing rate in Europe than other regions. Europe had an older population than all other regions and a higher prevalence of obesity than Africa, South East Asia and the Eastern Mediterranean. Country level multiple linear regression revealed positive associations between mortality/capita and testing rate, percent of the population 65 years or older, and Europe compared to Western Pacific and South East Asia (all P<0.005). Results for the analyses with cases/100,000 as outcome variable were similar. Conclusion: Our results suggest that older populations as well as other undefined regional and national factors, possibly related to efficacy of control efforts, are responsible for differences in national severity COVID-19 epidemics.

In December 2019, pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection emerged in Wuhan City, Hubei Province, China. Early in 2020, the World Health Organization (WHO) announced a new name for the 2019-nCoV-caused epidemic disease: coronavirus disease 2019 (COVID-19) and declared COVID-19 to be the sixth international public health emergency. Cellular co-infection is a critical determinant of both viral fitness and infection outcome and plays a crucial role in shaping the host immune response to infections. In this study, sixty-eight public next-generation sequencing libraries from SARS-CoV-2 infected patients were retrieved from the NCBI Sequence Read Archive database using SRA-Toolkit. Using an alignment-free method based on K-mer mapping and extension, SARS-CoV-2 was identified in all except three patients. Influenza A H7N9 (3/68), Human immunodeficiency virus 1 (1/68), rhabdovirus isolate (3/68), Human metapneumovirus (1/68), coronaviruses NL63 (1/68), Parvovirus (1/68), Simian virus 40 (1/68), and hepatitis virus (1/68) genome sequences were detected in SARS-CoV-2 infected patients.

Early detection, isolation, and management of COVID-19 patients are crucial to contain the current pandemic. The CDC in USA recently included "sudden loss of taste (dysgeusia/ageusia) and smell (anosmia/hyposmia)” as symptoms of COVID-19. If these symptoms are reliable forerunner symptoms of COVID-19, then it may facilitate early detection and containment of the disease. Hence, we systematically evaluated the contemporary evidence on dysgeusia and anosmia as trigger symptoms in COVID-19. Ovid MEDLINE, EBSCO host, and Web of Science databases were searched between December 25, 2019-May 30, 2020.Of the 13 identified records, eight (totaling 11,054 COVID-19 patients), were included, as per the selection criteria. The studies emanated mostly from the European community, as well as China, the USA, and Iran. In total, anosmia and dysgeusia symptoms were present in 74.9 % and 81.3% ambulatory as well as hospitalized, mild-to-severe cases of COVID-19 patients, respectively. The European, US, and Iran data indicate that olfactory, and gustatory symptoms appear prior to general COVID-19 symptoms in a majority of the patients. To our knowledge, this is the first systematic review analyzing the prevalence of chemosensory dysfunction in COVID-19. Further, studies are essential to evaluate their utility as harbingers of COVID-19 onset, and to establish clinical practice guidelines.

A compartmental epidemiological model with seven groups is introduced herein, to account for the dissemination of diseases similar to the Coronavirus disease 2019 (COVID-19). In its simplified version, the model contains ten parameters, four of which relate to characteristics of the virus, whereas another four are transition probabilities between the groups; the last two parameters enable the empirical modelling of the effective transmissibility, associated in this study with the cumulative number of fatalities due to the disease within each country. The application of the model to the fatality data (the main input herein) of five countries (to be specific, of those which had suffered most fatalities by April 30, 2020) enabled the extraction of an estimate for the basic reproduction number $R_0$ for the COVID-19 disease: $R_0=4.91(33)$.

Recent reports suggest that the clinical course of coronavirus disease 2019 (COVID-19) in previously healthy children is usually milder as compared to adults. However, children with comorbid conditions such as diabetes are at increased risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as morbidity and mortality due to COVID-19. Experience in adults with diabetes shows that they are prone to faster metabolic decompensation, develop diabetes-related complications, and have a poor prognosis when hospitalized with COVID-19. Data on children are limited. The aim of this mini-review is to discuss the possible risks to children and adolescents with diabetes during the current pandemic and the special considerations in management in those affected with COVID-19. The challenges for children who develop new-onset type 1 diabetes during the COVID-19 lockdown, especially in accessing healthcare, are also discussed.

Introduction: Due to the spread of SARS CoV-2 virus responsible for COVID-19 disease, there is an urgent need to analyse COVID-19 epidemic perception in Poland. This study aims to investigate social perception of coronavirus in the Internet media during the epidemic. It is a signal report highlighting the main issues in public perception and medical commutation in real time. Methods: We study the perception of COVID-19 epidemic in Polish society using quantitative analysis of its digital footprints on the Internet on platforms: Google, Twitter, YouTube, Wikipedia and electronic media represented by Event Registry, from January 2020 to 29.04.2020 (before and after official introduction to Poland on 04.03.20). We present trend analysis with a support of natural language processing techniques. Results: We identified seven temporal major clusters of interest on the topic COVID-19: 1) Chinese, 2) Italian, 3) Waiting, 4) Mitigations, 5) Social distancing and Lockdown, 6) Anti-crisis shield, 7) Restrictions releasing. There was an exponential increase of interest when the Polish government “declared war against disease” around 11/12.03.20 with a massive mitigation program. Later on, there was a decay in interest with additional phases related to social distancing and an anti-crisis legislation act with local peaks. We have found that declarations of mitigation strategies by the Polish prime minister or the minister of health gathered the highest attention of Internet users. So enacted or in force events do not affect interest to such extent. Traditional news agencies were ahead of social media (mainly Twitter) in dissemination of information. We have observed very weak or even negative correlations between a colloquial searching term 'antiviral mask' in Google, encyclopaedic definition in Wikipedia “SARS-CoV-2” as well official incidence series, implying different mechanisms governing the search for knowledge, panic related behaviour and actual risk of acquiring infection. Conclusions: Traditional and social media do not only reflect reality, but also create it. Risk perception in Poland is unrelated to actual physical risk of acquiring COVID-19. As traditional media are ahead of social media in time, we advise to choose traditional news media for a quick dissemination of information, however for a greater impact, social media should be used. Otherwise public information campaigns might have less impact on society than expected.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an etiologic agent of the respiratory disease in humans that is known as coronavirus disease 2019 (COVID19). The first outbreak of the disease was initially documented in Wuhan, Hubei Province, China in late December 2019 where people had experienced SARS pneumonia-like symptoms with unknown etiology. Since then it has been observed that COVID-19 positive patients have been showing mild to severe upper respiratory illness symptoms. The type of virus is known to make its transfer from animals to humans and for the concerned virus; researchers have claimed its origin from bat coronavirus at whole-genome level with a 96 % sequence identity. The COVID-19 virus is very contagious and communicable in nature and has been spread throughout the globe since its first outbreak in China. On March 9, 2020, WHO declared it as a Pandemic, and within a month it was already reported to have shown its presence in 213 countries and territories or areas. As of April 29, 2020, this novel virus infected 3,218,183 people and caused 228,029 mortalities worldwide with a variable mortality rate from 3-13 % across the planet and also varied by age and gender. Diagnosis of the disease is a key component in understanding and controlling the spread of the virus and several techniques have been devised including RT-PCR, ELISA, and sequencing-based approaches. To cure COVID-19 patients as of now we do not have proven to be a safe and effective treatment. Therapeutic options currently under investigation in various parts of the world. However, there are various effective therapeutic targets to repurpose the present antiviral therapy for developing potential interventions against SARS-CoV-2. Boosting the immune system can also help to prevent and spread of COVID-19 using various medication and exercises. In this review, our goal to summarize and discussed the present scientific advancements to fight against this novel pandemic.

Covid-19 has given a halt to all the activities in the world. Europe was most affected, followed by the United States of America. It has taken more than 350000 lives until now. In this study, we have assessed the severity of Covid-19 by analyzing the mortality rate of Covid-19 and other chronic diseases. The Covid-19 data and “death rate” data caused by other diseases were downloaded from the world health organization (WHO) website. A normalized method was used to see the mortality rate of Covid-19 in comparison to other diseases. The deaths caused by Covid-19 in April 2020 have overtaken the average number of deaths caused by Cancer, Cardiovascular diseases, and other diseases in Belgium, the United Kingdom (UK), Spain, France, and Ireland. Covid-19 was found to be strongly correlated with non-communicable respiratory diseases and Cancer with correlation coefficients 0.73 and 0.67 respectively. The severity of Covid-19 in the United States of America (USA) was moderate. The severity of Covid-19 in Asian countries was found to be low. Europe showed the highest diversity in the mortality rate of Covid-19. On average, except for a few European countries, Cardiovascular diseases, cancer, and non-communicable respiratory diseases were still more lethal and caused more deaths than Covid-19.

Reliable estimates of poplar plantations area are not available at the French national scale due to the unsuitability and low update rate of existing forest databases for this short-rotation species. While supervised classification methods have been shown to be highly accurate in mapping forest cover from remotely sensed images, their performance depends to a great extent on the labelled samples used to build the models. In addition to their high acquisition cost, such samples are often scarce and not fully representative of the variability in class distributions. Consequently, when classification models are applied to large areas with high intra-class variance, they generally yield poor accuracies. In this paper, we propose the use of active learning (AL) to efficiently adapt a classifier trained on a source image to spatially distinct target images with minimal labelling effort and without sacrificing classification performance. The adaptation consists in actively adding to the initial local model, new relevant training samples from other areas, in a cascade that iteratively improves the generalisation capabilities of the classifier, leading to a global model tailored to different areas. This active selection relies on uncertainty sampling to directly focus on the most informative pixels for which the algorithm is the least certain of their class labels. Experiments conducted on Sentinel-2 time series showed that when the same number of training samples was used, active learning outperformed passive learning (random sampling) by up to 5% of overall accuracy and up to 12% of class F-score. In addition, and depending on the class considered, the random sampling required up to 50% more samples to achieve the same performance of an active learning-based model. Moreover, the results demonstrate the suitability of the derived global model to accurately map poplar plantations among other tree species with overall accuracy values up to 14% higher than those obtained with local models. The proposed approach paves the way for national-scale mapping in an operational context.

Outbreaks of coronavirus disease 2019 (COVID-19) have been recorded in different countries across the globe. The virus is highly contagious, hence early detection, isolation, and quarantine of infected patients will play an important role in containing the viral spread. Diagnosis in a mobile lab can aid to find infected patients in time. Here, we develop a field-deployable diagnostic workflow that can reliably detect COVID-19. Instruments used in this workflow could easily fit in a mobile cabin hospital and also be installed in the community. Different steps from sample inactivation to detection were optimized to find the fastest steps and portable instruments in detection of COVID-19. Each step was compared to that of the normal laboratory diagnosis set-up. From the results, our proposed workflow (80 min) was two times faster compared to that of the normal laboratory workflow (183 min) and a maximum of 32 samples could be detected at each run. Additionally, we showed that using 1% Rewocid WK-30 could inactivate the novel coronavirus directly without affecting the overall detection results. Comparison of our workflow using an in-house assay to that of a commercially acquired assay produced highly reliable results. From the 250 hospital samples tested, there was a high concordance 247/250 (98.8%) between the two assays. The in-house assay sensitivity and specificity were 116/116 (100%) and 131/134 (97.8%) compared to that of the commercial assay. Based on these results, we believe that our workflow is fast, reliable, adaptable and most importantly, field deployable.

In the past decades, several new diseases have emerged in new geographical areas, with pathogens including Ebola, Zika, Nipah, and coronaviruses (CoVs). Recently, a new type of viral infection has emerged in Wuhan City, China, and initial genomic sequencing data of this virus does not match with previously sequenced CoVs, suggesting a novel CoV strain (2019-nCoV), which has now been termed as severe acute respiratory syndrome CoV-2 (SARS-CoV-2). Although Coronavirus disease 2019 (COVID-19) is suspected to originate from an animal host (zoonotic origin) followed by human-to-human transmission, the possibility of other routes such as food-borne transmission should not be ruled out. Compared to diseases caused by previously known human CoVs, COVID-19 shows less severe pathogenesis but higher transmission competence, as is evident from the continuously increasing number of confirmed cases globally. Compared to other emerging viruses such as Ebola virus, avian H7N9, SARS-CoV, or MERS-CoV, SARS-CoV-2 has shown relatively low pathogenicity and moderate transmissibility. Codon usage studies suggest that this novel virus may have been transferred from an animal source such as bats. Early diagnosis by real-time PCR and next-generation sequencing has facilitated the identification of the pathogen at an early stage. Since, no antiviral drug or vaccine exists to treat or prevent SARS-CoV-2, potential therapeutic strategies that are currently being evaluated predominantly stem from previous experience with treating SARS-CoV, MERS-CoV, and other emerging viral diseases. In this review, we address epidemiological, diagnostic, clinical, and therapeutic aspects, including perspectives of vaccines and preventive measures that have already been globally recommended.

Based on recent computational and experimental studies, hesperidin, a bioactive flavonoid abundant in citrus peel, stands out for its high binding affinity to the main cellular receptors of SARS-CoV-2, outperforming drugs already recommended for clinical trials. Thus, it is very promising for prophylaxis and treatment of COVID-19, along with other coexistent flavonoids such as naringin, which could help restraining the pro-inflammatory overreaction of the immune system. Controlled hydrodynamic cavitation processes showed the highest speed, effectiveness and efficiency in the integral and green aqueous extraction of flavonoids, essential oils and pectin from citrus peel waste. After freeze-drying, the extracted pectin showed high quality and excellent antioxidant and antibacterial activities, attributed to flavonoids and essential oils adsorbed and concentrated on its surface. This study reviews the recent evidence about hesperidin as a promising molecule, and proposes a feasible and affordable process based on hydrodynamic cavitation for the integral aqueous extraction of citrus peel waste resulting in hesperidin-rich products, either aqueous extracts or pectin tablets. The uptake of this process on a relevant scale is urged, in order to achieve large-scale production and distribution of hesperidin-rich products. Meanwhile, experimental and clinical studies could determine the effective doses either for therapeutic and preventive purposes.

More than 179,000 individuals have fallen ill of the Coronavirus disease (COVID-19) caused by the SARS-CoV-2 virus, which first emerged in China less than four months ago in December 2019. As of today, there exist no approved treatments against COVID-19. Vaccines are being developed, but they will take time, at least one year, to reach the population. Drug repositioning represents a fast track because already approved medicines have been broadly tested through multiple trials. We developed a repositioning strategy that mostly leads to candidates that are commonly used. The advantages are that they will facilitate proof of concept in humans through a “real-world evidence” approach and should be rapidly available to the population. We focus on the established research results that the unfolded protein response (UPR) and autophagy pathways of the host cells are essential to the life cycle of previously known coronaviruses. We performed the relevant bioinformatics analysis to understand and confirm if SARS-CoV-2 may interact with these druggable pathways. Based on these considerations, we prioritized two additional druggable pathways, which are important to the viral life cycle and tightly connected to UPR/autophagy signaling: the mitochondrial permeability transition pores (MPTP) and NLRP-3 inflammasome pathways. These four important pathways are perturbed in most major common diseases and have therefore been targeted by numerous broadly prescribed drugs. We have identified 97 approved drugs that are known to modulate these four identified pathways, and which represent, therefore, interesting repositioning candidates. Although it is indisputable that these drugs should never be used for immediate self-medication against COVID-19, we notice that some of them could also be prescribed to individuals who have COVID-19 comorbidities (e.g., hypertension). It is debated if these comorbidities are linked to the pathology itself (e.g., hypertension) or the drugs used to treat the pathology (e.g., sartans). Therefore, relevant preclinical tests and massive electronic health records (i.e., real-world evidence) must be used to pre-screen them and check the COVID-19 prognosis of individuals taking these drugs.

The spike protein of SARS coronavirus (SARS-CoV) attaches the virus to its cellular receptor, angiotensin-converting enzyme 2 (ACE2), which is mediated by the receptor binding domain (RBD) of the spike protein. Recently, an analysis based on decade-long structural studies of SARS was reported to illustrate with atomic-level details receptor recognition by the novel coronavirus from Wuhan, i.e., 2019-nCoV. Here, this article reports a comprehensive set of structural electrostatic analysis of all SARS-CoV spike protein RBD-related structures as of February 13, 2020, aiming at identifying the electrostatic hot spots for SARS-CoV spike protein to be complexed with ACE2 and its neutralizing antibodies. First, this article identified a structural action mechanism of the F26G19 antibody (of SARS-CoV spike protein), where its Asp56 residue binds to the Arg426 of the SARS-CoV spike protein RBD against the formation of the interfacial Arg426-Glu329 salt bridges between ACE2 and the SARS-CoV spike protein RBD. Second, a hypothesis is reported that a pair of electrostatic clips exist at the interface between ACE2 and the SARS-CoV spike protein RBD, including both Arg426-Glu329 and His445-Glu23-Lys447 salt bridges. Last, this article reports a structurally identified interfacial Glu35-Arg479 salt bridge which helps stabilize the complex structure of ACE2 and the SARS-CoV spike protein RBD. Overall, the structurally identified electrostatic hot spots reported here may be useful for the design of SARS-CoV-neutralizing antibodies in future.

Easy to use satellite-based water quality visualizations are needed for monitoring and understanding coastal and inland waters, but to date, no publicly accessible real-time global visualization system was in place. Here we introduce the Ulyssys Water Quality Viewer (UWQV), a Sentinel Hub EO Browser Custom script designed for qualitative views of aquatic chlorophyll and suspended sediment concentrations. The viewer avoids unmixing of the chlorophyll and suspended sediment spectral signal by visualizing these parameters together, with high concentrations of suspended sediment obscuring chlorophyll if present. Cloud masking uses the Hollstein and Braaten algorithms (existing EO Browser custom script code), additionally water surfaces are masked using the Normalized Differential Water Index. Chlorophyll is estimated using reflectance line height-based indicators such as fluorescence line height and maximum chlorophyll index. Suspended sediment is visualized based on single-band reflectances at 620 or 700 nm. Data sources are Sentinel-2 and Sentinel-3 images, allowing either 20 m spatial resolution or up to daily imaging. This visualization system is easy to operate and interpret, and combined with the data service capacity of the Sentinel Hub, it is expected that UWQV will contribute to monitoring of remote water bodies and to our overall understanding of physical limnology and aquatic ecology.

The epithelial cell tight junction structure is the site of the transepithelial movement of solutes and water between epithelial cells (paracellular permeability). Paracellular permeability can be divided into two distinct pathways, the Pore Pathway mediating the movement of small ions and solutes and the Leak Pathway mediating the movement of large solutes. Claudin proteins form the basic paracellular permeability barrier and mediate the movement of small ions and solutes via the Pore Pathway. The Leak Pathway remains less understood. Several proteins have been implicated in mediating the Leak Pathway, including occludin, ZO proteins, tricellulin, and actin filaments, but the proteins comprising the Leak Pathway remain unresolved. The properties of the Leak Pathway, such as its molecular mechanism, its regulation, and whether or not it has a size limit, remain controversial. This review will trace the evolution of the Leak Pathway concept from its origins, will discuss the current information about the properties of the Leak Pathway, and will discuss recent research suggesting a possible molecular basis for the Leak Pathway. Based on these findings, we propose a model for the molecular mechanism underlying the Leak Pathway and its regulation.

Common genetic variants of the fat mass and obesity associated (FTO) gene are strongly associated with obesity and type 2 diabetes. FTO is ubiquitously expressed, but appears to have tissue-specific roles. Earlier studies have focused on the role of hypothlamic FTO in the regulation of metabolism. However, it appears that FTO plays a role in the regulation of metabolism in a tissue-specific manner. Recent studies suggest that expression of hepatic FTO is regulated by metabolic signals such as nutrients and hormones and altered FTO levels in liver affects glucose and lipid metabolism. This review outlines recent findings on hepatic FTO in the regulation of metabolism, with particular focus on hepatic glucose and lipid metabolism. It is proposed that abnormal activity of hepatic signaling pathways involving FTO links metabolic impairments such as obesity, type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). Therefore, a better understanding of these pathways may lead to therapeutic approaches to treat these metabolic diseases by targeting hepatic FTO. The overall goal of this review is to place FTO within the context of hepatic regulation of metabolism.

Ischemic neuron loss contributes to brain dysfunction in patients with cardiac arrest (CA). Histidine–tryptophan–ketoglutarate (HTK) solution is a preservative used during organ transplantation. Can HTK also protect neurons from severe hypoxia (SH) following CA? We isolated rat primary cortical neurons and induced SH with or without HTK. Changes in caspase-3, hypoxia-inducible factor 1-alpha (HIF-1α), and NADPH oxidase-4 (NOX4) expression were evaluated at different time points till 72 h. Using a rat asphyxia model, we induced CA-mediated brain damage and then completed resuscitation. HTK or sterile saline was administered into the left carotid artery. Neurological deficit scoring and mortality were evaluated for 3 days. Then the rats were sacrificed for evaluating NOX4 and H2O2 level in blood and brain. In the in vitro study, HTK attenuated SH- and H2O2-mediated cytotoxicity in a volume- and time-dependent manner, associated with persisted HIF-1α expression, reductions in procaspase-3 activation and NOX4 expression. The inhibition of HIF-1α abrogated HTK’s effect on NOX4. In the in vivo study, neurological scores were significantly improved by HTK. H2O2 level, NOX4 activity and NOX4 gene expression were all decreased in the brain specimen of HTK-treated rats. Our results suggest that HTK acts as an effective neuroprotective solution.

Hypothesis: Anti-diabetic drugs modulate p-21 activated kinase (PAK) signaling Introduction: Type 2 diabetes mellitus (T2DM) is a chronic inflammatory disease associated with increased cancer risk. PAK signaling is implicated in cellular homeostasis when regulated, and cancer when unrestrained. Recent reports provided a role for PAK signaling in glucose homeostasis, but the role of PAKs in the pathogenesis of T2DM is unknown. Here we performed a mini-meta analysis to explore if anti-diabetic drugs modify PAK signaling pathways, and provide insight regarding modulation of these pathways to potentially reduce diabetes-associated cancer risk. Methods: PAK interacting partners in T2DM were identified using online STRING database. Correlation studies were performed via systematic literature review to understand the effect of anti-diabetic drugs on PAK signaling. Mini meta analysis correlated multiple clinical studies and revealed the overall clinical response rate and percentage of adverse events in piogliazone (n=53) and metformin (n=91) treated patients with PAK-associated diseases. Results: A total of 30 PAK interacting partners were identified (10: reduced beta-cell mass; 10: beta-cell dysfunction; 10: obesity-insulin resistance) which were highly associated with Wnt, and G-protein signaling. Anti-diabetic drug metformin activated signaling pathways upstream; whereas pioglitazone inhibited pathways downstream of PAK. Overall clinical response upon pioglitazone treatment was 53%. 79% of pioglitazone and 75% of metformin treated patients had adverse events. Pioglitazone reduced molecular-PAK biomarkers of proliferation (Ki67 and CyclinD1), and metformin had the opposite effect. Conclusions: PAK signaling in T2DM likely involves Wnt and G-protein signaling which may be altered by anti-diabetic drugs metformin and pioglitazone. Apart from the therapeutic limitations of adverse events, pioglitazone may be promising in chemoprevention, however long-term multi-centered studies, which initiate pioglitazone treatment early will be required to fully assess the full potential of these drugs.

Hypothesis: Anti-diabetic drugs modulate p-21 activated kinase (PAK) signaling Introduction: Type 2 diabetes mellitus (T2DM) is a chronic inflammatory disease associated with increased cancer risk. PAK signaling is implicated in cellular homeostasis when regulated, and cancer when unrestrained. Recent reports provided a role for PAK signaling in glucose homeostasis, but the role of PAKs in the pathogenesis of T2DM is unknown. Here we explored whether PAK signaling should be targeted via chemoprevention to reduce diabetes-associated cancer risk. Methods: PAK interacting partners in T2DM were identified using online STRING database. Systematic literature review provided the effect of anti-diabetic drugs on PAK signaling. Review of clinical studies revealed the overall clinical response rate and percentage of adverse events in piogliazone (n=53) and metformin (n=91) treated patients with PAK-dependent diseases. Results: A total of 30 PAK interacting partners were identified (10: reduced beta-cell mass; 10: beta-cell dysfunction; 10: obesity-insulin resistance) which were highly associated with Wnt, and G-protein signaling. Anti-diabetic drug metformin activated signaling pathways upstream; whereas pioglitazone inhibited pathways downstream of PAK. Overall clinical response upon pioglitazone treatment was 53%. 79% of pioglitazone and 75% of metformin treated patients had adverse events. Pioglitazone reduced molecular-PAK biomarkers of proliferation (Ki67 and CyclinD1), and metformin had the opposite effect. Conclusions: PAK signaling in T2DM involves Wnt and G-protein signaling which is altered by anti-diabetic drugs metformin and pioglitazone. Apart from the therapeutic limitations of adverse events, pioglitazone is promising in chemoprevention, however long-term multi-centered studies, which initiate pioglitazone treatment early will be required to fully assess the full potential of these drugs.

The aim of this study was to examine oxidative stress and low level of alpha-1-antitrypsin (A1AT) in primary Sjögren's syndrome (pSS), and evaluate the associated autoreactivity against unmodified and their 4-hydroxy-2-nonenal (HNE)-modified peptides with pSS. Two differentially expressed proteins, alpha-1-acid glycoprotein 1 (A1AG1) and A1AT, exhibited 2-fold differences, and their HNE modifications were identified by depleted-albumin and immunoglobulin G (IgG) serum protein, in-solution digestion, in-gel digestion, and nano-LC-MS/MS from pSS patients and age-matched healthy controls (HCs). Furthermore, levels of proteins, confirmation of HNE modifications, HNE-protein adducts and autoreactivity against unmodified and their HNE-modified peptides were further validated. Levels of the HNE-protein adduct and A1AG1 were significantly higher in pSS patients than HCs, but levels of A1AT were significantly lower in pSS patients compared to HCs. Only the HNE modification of A1AT was confirmed. Further, concentrations of anti-A1AT^50-63 IgG and anti-A1AT^50-63 HNE IgA were significantly lower in pSS patients than HCs. Our study suggests that elevated HNE-protein adduct, oxidative stress, level [odds ratio (OR) 4.877, p = 0.003], lowered A1AT level (OR 3.910, p = 0.010) and a decreased level of anti-A1AT^50-63 IgG (OR 3.360, p = 0.010) showed an increased risk in pSS patients compared to HCs, respectively.

Splines and quasi-interpolation operators are important both in approximation theory and applications. In this paper, we construct a family of quasi-interpolation operators for the bivariate quintic spline spaces S₅³ (∆_mn⁽²⁾). Moreover, the properties of the proposed quasi-interpolation operators are studied, as well as its applications for solving two-dimensional Burgers’ equation and image reconstruction. Some numerical examples show that these methods, which are easy to implement, provide accurate results.

Background/Objectives: Dengue is an arbovirus caused by a virus. It is an endemic infectious and occurs in warmer climates. It is not uncommon for the disease to be asymptomatic. However, the severe form can also be triggered and require intensive care. In this sense, patients present a wide variety of symptoms, which can trigger comorbidities such as arthritis, hematologic diseases, liver diseases, kidney diseases, autoimmune diseases, and, mainly, diabetes and hypertension. Among the symptoms, the presence of fever, myalgia, headache, nausea, vomiting, leukopenia, petechiae, retroorbital pain, arthralgia, rashes, skin eruptions, cardiovascular symptoms, respiratory symptoms and, depending on the severity, the presence of hemorrhages may occur. Methods: 235 patients' anonymized records from a secondary hospital were analyzed. Ethics approval was obtained and no patients’ consent was needed. Statistical analysis used frequency distributions and Chi-square tests, with SPSS software. Results: Similar to other studies, our results show that dengue can lead to complications. Furthermore, there was no significant difference in the distribution of the proportion of symptoms between patients with positive and negative serology. However, there was a significant association between age group and symptoms of fever and myalgia, with the occurrence of fever decreasing with increasing age and myalgia being more frequent in adults and less frequent in those &lt;10 years old. Conclusions: Dengue can lead to complications, with fever becoming less common and muscle pain increasing as people age. Climate change could spread dengue to new areas. To address this, we need better vaccines and more effective mosquito control.

Developing short-term forecasting model for global atmospheric temperature and wind in the near space is crucial for understanding atmospheric dynamics and supporting human activities in this region. While numerical models have been extensively developed, deep learning techniques have recently shown promise in improving atmospheric forecasting accuracy. In this study, convolutional long short-term memory (ConvLSTM) and convolutional gated recurrent unit (ConvGRU) neural networks were applied to build for short-term global-scale forecasting model of atmospheric temperature and wind in the `near space based on the MERRA-2 reanalysis dataset from 2010-2022. The model results showed that the ConvGRU model outperforms the ConvLSTM model in the short-term forecast results. The ConvGRU model achieved a root mean square error in the first three hours of approximately 1.8 K for temperature predictions, and errors of 4.2 m/s and 3.8 m/s for eastward and northward wind predictions, respectively.

The COVID-19 pandemic has revealed significant disparities in disease severity and mortality across various population groups and regions. These disparities cannot be attributed solely to healthcare systems, socioeconomic factors, living conditions, or individual immune landscapes; environmental factors also play a crucial role. This work explores how variations in nasal morphology related to age, gender, and race can affect the respiratory system's ability to filter, warm, and humidify inhaled air. These variations may contribute to differences in how cold, dry, polluted, and infected air impact the respiratory system, thus influencing the observed patterns of disparities in COVID-19 outcomes. The analysis suggests that individuals with genetically determined wider nasal cavities, often found in populations originating from warmer climates, have decreased filtration and air conditioning efficiency, leading to increased susceptibility to respiratory infections and disproportionately high mortality rates from COVID-19. Moreover, age-related changes in nasal morphology, such as increased nasal volume and involution atrophy of the mucosa, contribute to impaired air conditioning and filtration, thereby increasing the risk of severe outcomes in the elderly. Gender differences in nasal morphology, with men typically having larger nasal passages compared to women, are linked to poorer air conditioning and filtration, potentially contributing to the higher risk of severe COVID-19 in men. Preliminary statistical analyses of the U.S. population suggest that men with favorable nasal structures may have a longer life expectancy than those with less optimal nasal anatomy; however, this should be regarded as a hypothesis. The findings underscore significant gaps in our understanding and highlight the urgent need for further research to unravel the complex interplay between nasal morphology, respiratory system dynamics, and environmental factors in shaping disease susceptibility and outcomes.

We present first-principles DFT+U investigation of the bulk properties including structural, energetic and mechanical properties for uranium-americium mixed oxides (U, Am)O₂. The various Am aggregation contents have been investigated to better understand the impact of Am in the nuclear fuel UO₂. The supercell defect models at different scales were used to describe the solid solution (U, Am)O₂. The obtained results show that different contents of Am has a significant impact on the volume and energy of the mixed oxides systems. The results on the electronic structure calculations exhibit a narrow band gap owing to the mixing of UO₂ and AmO₂. The mixing enthalpy of the Am aggregation systems are used to describe the phase stability for the solid solution. In particular, mixing enthalpy of the (U, Am)O₂ significantly reduced as the Am content increases. The elastic properties of the (U, Am)O₂ mixed oxides have also been compared as a function of Am content. Moreover, the impacts of the whole Pu aggregation content range on the bulk properties for the (U, Pu)O₂ mixed oxides is also discussed.

The emergence of mRNA vaccines for SARS-CoV-2 has opened a new page in vaccine development; nevertheless, concerns of the experts have been expressed about unintentional side effects on the gut microbiota (GM). Previous studies showed that this virus acts as a bacteriophage, which infects and destroys specific bacterial strains in the GM. The present manuscript hypothesizes that the synthetic spike protein could create changes in the composition and the functioning of the GM by entering the intestinal cells after vaccination and impairing the symbiotic relationship between intestinal cells and the GM. An experimental protocol to test the hypothesis is suggested.

The conservation of the main protease in viral genomes, combined with the absence of a homologous protease in humans, makes this enzyme family an ideal target for developing broad-spectrum antiviral drugs with minimal host toxicity. GC-376, a peptidomimetic 3CL protease inhibitor, has shown significant efficacy against coronaviruses. Recently, a GC-376-based PROTAC was developed to target and induce the proteosome-mediated degradation of the dimeric SARS-CoV-2 3CLPro protein. Extending this approach, the current study investigates the application of the GC-376 PROTAC to the 3CPro protease of Enteroviruses, specifically characterizing its interaction with CVB3 3CPro through X-ray crystallography, NMR and biophysical techniques. The present structural data show that there are some changes between the binding of CVB3 3CPro and SARS-CoV-2 3CLPro, but the overall similarity is strong. The most notable variation is the orientation of the phenylmethyl ester of GC-376 with the S4 subsite of the proteases. This is linked to the flexibility of the protein structure around the region of the catalytic triad shown by our NMR data. Other structural variations include distinct ligand interactions in subsites S1 and S2, influenced by the presence of Glu71 in CVB3 3CPro. Despite these differences, the GC-376 PROTAC fits well within the binding sites of both proteases, demonstrating its potential as a broad-spectrum antiviral agent.

Alginate-silver nanocomposites in the form of spherical beads and films were prepared using a green approach by using the aqueous extract of Ajwa dates seeds. The nanocomposites were fabricated by in situ reduction and gelation method by ionotropic crosslinking using calcium ions in solution. The rich phytochemicals of the dates seeds extract played a dual role as reducing and stabilizing agent in the synthesis of silver nanoparticles. The formation of silver nanoparticles was studied using UV-Vis absorption spectroscopy and a distinct surface plasmon resonance (SPR) peak at 421 nm characteristic of silver nanoparticles confirmed the green synthesis of silver nanoparticles. The morphology of the nanocomposite beads and film was compact with even distribution of silver nanoclusters. The catalytic property of the nanocomposite beads was evaluated for the degradation of 2-nitrophenol in the presence of sodium borohydride. The degradation followed pseudo-first order kinetics with a rate constant of 1.40 ´ 10^-3 s^-1 at 23 °C with an activation energy of 18.45 kJ mol^-1. The thermodynamic parameters such as changes in enthalpy and entropy were evaluated to be 15.22 kJ mol^-1 and -197.50 J mol^-1 K^-1, respectively. The nanocomposite exhibited properties against three clinically important pathogens (Gram-positive and Gram-negative bacteria)

In the global carbon cycle, atmospheric carbon emissions, both ‘natural’ and anthropogenic, are balanced by carbon uptake (i.e. sequestration) that mostly occurs via photosynthesis, plus a much smaller proportion via geological processes. Since the formation of the Earth about 4.54 billion years ago the ratio between emitted and sequestered carbon has varied considerably with atmospheric CO₂ levels ranging from 100,000 ppm to a mere 100 ppm. Over this time, a huge amount of carbon has been sequestered due to photosynthesis and essentially removed from the cycle, being buried as fossil deposits of coal, oil and gas. Relatively low atmospheric CO₂ levels were the norm for the past 10 million years, and during the past million years they averaged about 220 ppm. More recently, the Holocene epoch, starting ~11,700 years ago, has been a period of unusual climatic stability with relatively warm, moist conditions and low atmospheric CO₂ levels of between 260 and 280 ppm. During the Holocene, stable conditions facilitated a social revolution with domestication of crops and livestock leading to urbanisation and development of complex technologies. As part of the latter process, immense quantities of sequestered fossil carbon have recently been used as energy sources, resulting in a particularly rapid increase in CO₂ emissions after 1950 CE to the current value of 424 ppm, with further rises to >800 ppm predicted by 2100. This is already perturbing the previously stable Holocene climate and threatening future food production and social stability. Today, the global carbon cycle has been shifted such that carbon sequestration is no longer keeping up with recent anthropogenic emissions. In order to address this imbalance it is important to understand the roles of high-capacity carbon sequestration systems, such as natural forests and tropical croplands, and to devise strategies to facilitate net CO₂ uptake.

This study aimed to develop a laboratory-scale direct air capture unit for evaluating and comparing amine-based adsorbents under temperature vacuum swing adsorption conditions. The experimental campaign conducted with the direct air capture unit allowed for the determination of equilibrium loading, CO2 uptake capacity, and other main performance parameters of the investigated adsorbent Lewatit VP OC 1065®. The investigations also helped to understand the co-adsorption of both CO2 and H2O on the tested material, which is crucial for improving temperature vacuum swing adsorption processes. This was achieved by obtaining pure component isotherms for CO2 and H2O as well as three different co-adsorption isotherm models from literature. It was found that the weighted average dual-site Toth model emerged as the most accurate and reliable model for simulating this co-adsorption behavior. Its predictions closely align with experimental data, particularly in capturing the adsorption equilibrium at various temperatures. It was also observed that this lab-scale unit offers advantages over thermogravimetric analysis when conducting adsorption experiments on the chosen amine. The final aim of this study is to provide a pathway to develop devices for testing and developing efficient and cost-effective adsorbents for direct air capture.

The increased prevalence of obesity worldwide has been implicated for the alarming rise of the incidence of gestational diabetes and preeclampsia as well, both considered as threatening conditions for both mother and fetus. We studied gene polymorphisms of the proinflammatory cytokine Interleukin 6 (IL-6) and the gene expression levels of VEGF and VEGF-receptor all known to be involved in pregnancy complications aiming to identify possible predisposing risk factors in pregnancies with obesity. G allele of IL-6 was found to correspond with an increased risk for gestational diabetes and preeclampsia occurrence. Furthermore, in obese pregnant mothers with either gestational diabetes or pre-existing type 2 diabetes and to those developed preeclampsia it was confirmed that gene expression levels of VEGF were reduced while they were increased for VEGF receptor. We conclude that the genetic profile of the obese pregnant woman shares a common background with that of a pre-existing type 2 diabetes mellitus and therefore predisposes to complications in pregnancy.

Semenov-Tian-Shansky has introduced the modified classical Yang-Baxter equation, which is called the modified $r$-matrix. Relevant studies have been extensive in recent times. This paper is devoted to study cohomology theory of modified Rota-Baxter pre-Lie algebras and its applications. First we introduce the concept and representations of modified Rota-Baxter pre-Lie algebras. We then develop the cohomology of modified Rota-Baxter pre-Lie algebras with coefficients in a suitable representation. As applications, we consider the infinitesimal deformations, abelian extensions and skeletal modified Rota-Baxter pre-Lie 2-algebra in terms of lower degree cohomology groups.

The quality of healthcare services is a very important indicator of social welfare in developed and emerging countries. Good quality levels are critical to ensuring patient safety, improving health outcomes, increasing patient satisfaction, optimizing resource utilization, and meeting regulatory requirements. The stable and sustainable operation of medical institutions urgently requires the establishment of a reliable and effective medical quality performance evaluation platform. However, the complexity of the evaluation process, involving numerous evaluators and the consideration of different subjective and objective criteria, poses significant challenges and essentially constitutes a group multi-criteria decision-making problem. This article uses the overall medical environment of the institution, medical service attitude, medical security, administrative service measures, etc. as measurement standards to deal with this challenge. It proposes a medical service quality measurement model suitable for both qualitative and quantitative analysis. In view of the heterogeneity of information, the two-tuple fuzzy language calculation method is introduced to enable evaluators to skillfully manage diverse information and effectively avoid potential information omission problems in the subjective evaluation integration process. The effectiveness and feasibility of the model were demonstrated by applying it to the operational framework of a medical institution in central Taiwan.

The sheer number of gene variants and the extent of the observed clinical and molecular heterogeneity recorded in neuropsychiatric disorders (NPDs), could be due to the magnified downstream effects initiated by a smaller group of genomic higher order alterations in response to endogenous or environmental stress. Chromosomal common fragile sites (CFS) are functionally linked with microRNA’s, gene copy number variants (CNVs), sub-microscopic deletions and duplications of DNA, rare single-nucleotide variants (SNVs/SNPs) and small insertions/deletions (indels), as well as chromosomal translocations, gene duplications, altered methylation, microRNA and L1 transposon activity and 3-D chromosomal topology characteristics. These genomic structural features have been linked with various NPDs in mostly isolated reports, and have usually only been viewed as areas harboring potential candidate genes of interest. The suggestion to use a higher level entry point, (the ‘fragilome’ and associated features), activated by a central mechanism (‘stress’) for studying NPD genetics, has the potential to unify the existing vast number of different observations in this field. This approach may explain the continuum of gene findings distributed between affected and unaffected individuals, the clustering of NPD phenotypes and overlapping comorbidities, the extensive clinical and molecular heterogeneity and the association with certain other medical disorders.

This study aimed to elucidate the similarities and differences between amyloid-forming corpora amylacea (CA) in the prostate and lung, examine the nature of CAs in cystic tumors of the atrioventricular node (CTAVN), and clarify the distinctions between amyloid-forming CA and spheroid-type amyloid deposition. We conducted proteomics analyses using liquid chromatography–tandem mass spectrometry with laser microdissection and immunohistochemistry to validate the characteristics of CAs in the lung and prostate. Our findings revealed that CAs in these organs primarily consist of common proteins (β2-microglobulin and lysozyme) and locally produced proteins. Moreover, we observed a discrepancy between the histopathological and proteomic analysis results in CTAVN-associated CAs. In addition, while the histopathological appearance of amyloid-forming CAs and spheroid-type amyloid deposits were nearly identical, the latter deposition lacked β2-microglobulin and lysozyme, and exhibited evident destruction of surrounding tissue. A literature review further supported these findings. These results suggest that amyloid-forming CAs in the lung and prostate are formed through a shared mechanism, serving as waste containers (wasteosomes) and/or storage for excess proteins (functional amyloids). In contrast, we hypothesize that while amyloid-forming CA and spheroid-type amyloid deposits are formed, in part, through common mechanisms, the latter are pathological.

Alzheimer’s Disease (AD), a progressive and debilitating condition, is reported to be the most common type of dementia, with at least 55 million people believed to be currently affected. Many causation hypotheses of AD exist, yet the intriguing link between viral infection and its possible contribution to the known etiology of AD has become an attractive focal point of research for the field and a challenging study task. In this review, we will explore the historical perspective and milestones that led the field to investigate the viral connection to AD. Specifically, several viruses such as Herpes Simplex Virus 1 (HSV-1), Zika virus (ZIKV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), along with several others mentioned, include the various viruses presently considered within the field. We delve into the strong evidence implicating these viruses in the development of AD. We will also extend beyond these mere associations by carefully analyzing the potential mechanisms by which viruses may contribute to AD pathology. This includes but is not limited to direct neuronal infections, dysregulation of immune responses, and the impact on protein processing. Controversies and challenges of the viral-AD relationship emerge as we tease out these potential mechanisms considered. Looking forward, we emphasize the future directions the field should take to tackle the remaining unanswered questions and the glaring research gaps that persist. Overall, this review aims to provide a comprehensive survey of the past, present, and future of the potential link between viral infections and their association with AD development.

Wastewater-Based Epidemiology (WBE) is currently used to monitor not only the spread of the pandemic virus SARS-CoV-2 but also for other viruses in endemic conditions, particularly in the absence of syndromic surveillance. Continuous monitoring of sewage requires high costs and significant time investment, highlighting the need for standardized methods and structured monitoring strategies. In this context, we conducted weekly wastewater monitoring in northwestern Italy, targeting Human Adenovirus (HAdV), Norovirus Genogroup II (NoVggII), Enterovirus (EV), and SARS-CoV-2. Samples collected at the entrance of treatment plants were concentrated using PEG/NaCl precipitation and viral nucleic acids were extracted and detected by real-time (RT-)qPCR. NoVggII resulted the most identified target (84.4%), followed by HAdV, SARS-CoV-2, and EV. Only HAdV and EV exhibited seasonal peaks in spring and summer. SARS-CoV-2 results compared with data previously collected in the same study area (February 2021 to September 2021) revealed a shift from an epidemic to a pandemic status, likely due to the evolution of variants. In conclusion, WBE, using standardized methods and an efficient monitoring strategy, proves valuable for virus surveillance in pandemic and epidemic scenarios, enabling the identification of temporal-local distribution patterns that are useful for making informed public health decision.

This study investigates the influence of economic growth on CO2 emissions levels in three developed countries—Argentina, Equatorial Guinea, and South Korea—based on their status as high-income countries. We test the environmental Kuznets curve (EKC) hypothesis using the time series approaches to check the relationship and direction of causality among the variables over a sample spanning 1974–2020. The results show an inverted U-shaped short-run relationship in all three countries. In the long run, only South Korea supports the EKC hypothesis. Further, Granger causality results indicate the existence of causality. These long-run causal relationships between economic growth and emissions recommend one policy implication that wealthy governments must expand investments in renewable clean energy projects and R&D, with regulatory measures to suppress harmful environmental procedures and support environmentally friendly development.

This article systematically reviews the research achievements on the MnOx/TiO2 catalyst doped with transition metals or rare earth metals for the catalytic selective catalytic reduction of NH3 (SCR-NH3) reaction. The Methodi Ordinatio systematic literature analysis method was employed to rank relevant articles based on journal impact factors, publication years, and citation counts. The ranking data shows that the undoped MnOx/TiO2 catalysts exhibit a catalytic efficiency of up to approximately 90% for NOx reduction, while the doped MnOx/TiO2 catalysts with transition metals or rare earth metals can achieve a maximum reduction efficiency of 100%. Among all the doped metals, the catalyst doped with nickel demonstrates the best NOx reduction performance. The comprehensive literature research concludes that MnOx/TiO2-based SCR catalysts, especially those doped with transition metals or rare earth metals, have significant catalytic efficiency and development potential in reducing NOx emissions in SCR reactions.

The symmetries of a Riemann surface $\Sigma \setminus \{a_i\}$ with $n$ punctures $a_i$ are encoded in its fundamental group $\pi_1(\Sigma)$. Further structure may be described through representations (homomorphisms) of $\pi_1$ over a Lie group $G$ as globalized by the character variety $\mathcal{C}=\mbox{Hom} (\pi_1,G)/G$. Guided by our previous work in the context of topological quantum computing (TQC) and genetics, we specialize on the $4$-punctured Riemann sphere $\Sigma=S_2^{(4)}$ and the \lq space-time-spin' group $G=SL_2(\mathbb{C})$. In such a situation, $\mathcal{C}$ possesses remarkable properties (i) a representation is described by a $3$-dimensional cubic surface $V_{a,b,c,d}(x,y,z)$ with $3$ variables and $4$ parameters, (ii) the automorphisms of the surface satisfy the dynamical (non linear and transcendental) Painlev\'e VI equation (or $P_{VI}$), (iii) there exists a finite set of $1$ (\mbox{Cayley-Picard})+$3$ (\mbox{continuous platonic})+$45$ (\mbox{icosahedral}) solutions of $P_{VI}$. In this paper we feature on the parametric representation of some solutions of $P_{VI}$, (a) solutions corresponding to algebraic surfaces such as the Klein quartic and (b) icosahedral solutions. Applications to the character variety of finitely generated groups $f_p$ encountered in TQC or DNA/RNA sequences are proposed.

As yin and yang, cancer and diabetes are metabolic disorders characterized by deregulated, yet opposing, metabolic alterations. These metabolic shifts reflect a complex network of defective underlying signaling pathways, which ultimately orchestrate both disease pathogenesis and progression. The Warburg effect portrays the chief metabolic phenotype in cancer and is reflected by the dominance of aerobic glycolysis over minimal-to-no viable oxidative phosphorylation in cancer. Conversely, during the pathogenesis of type 2 diabetes (T2D), oxidative phosphorylation is constantly heightened. In advanced insulin resistance and T2D, the metabolic landscape becomes more complex, with exacerbating metabolic alterations affecting oxidative phosphorylation in a tissue-specific manner. Promising nutritional adjuvants, such as alpha-lipoic acid and flavonoids, can reprogram metabolism and exert antitumor and antidiabetic effects. Other pharmacological agents, such as metformin, have therapeutic effects on cancer and T2D. Herein, we discuss the molecular mechanisms and signaling pathways involved in the metabolic shifts in cancer and T2D, and explore the therapeutic strategies under investigation that aim to reverse the metabolic shift in both disease scenarios.

The removal of H2S from natural gas and other gases such as biogas, refinery gases, and coal gas is required because H2S is toxic and corrosive, even in traces. Zeolites are widely used in the removal of H2S from the above-mentioned gases. In this work, we prepared an Ag-exchanged 13X molecular sieve by using different concentrations of AgNO3 to increase its adsorption properties. XRD, SEM, and BET techniques were used to characterize samples. When compared to unmodified 13X, the adsorption capacity of AgII-13X increased by about 50 times. The results of this study suggest that the silver-modified 13X molecular sieve is highly effective at extracting H2S from natural gas.

Cadmium (Cd) is a pervasive toxic metal, present in most food types, cigarette smoke, and contaminated air. It has no nutritional or physiological value, but most cells in the body will assimilate Cd, as its charge and ionic radius are similar to the essential metals, iron, zinc, and calcium (Fe, Zn, Ca), which are required for cellular metabolism and functional integrity. The kidney is regarded as the principal site of Cd toxicity as it preferentially accumulates in the proximal tubular epithelium here. As these cells die due to toxic accumulation, Cd complexed with metallothionein are released into tubular lumen and excreted. Excretion of Cd, signifying current renal cell toxicity, is used as a measure of long-term Cd exposure. Approximately 10% of the global population are now living with diabetes and over 80% of these are overweight or obese. This association has fueled an intense search for any exogenous chemicals and life-style factors that could induce excessive weight gain. Whilst epidemiological studies have clearly linked diabetes to Cd exposure, this appears to be independent of obesity. Indeed, obesity may enhance diabetogenic effects of Cd. This review highlights Cd exposure sources and levels associated with diabetes type 2 along with the pathophysiologic mechanisms by which Cd disrupt glucose metabolism. Special emphasis is on roles of the liver and kidney in glucose homeostasis, heme-glucose cross-talk, and the involvement of heme oxygenase-1 and -2 (HO-1 and HO-2). From heme degradation, both HO-1 and HO-2 release Fe, carbon monoxide and a precursor substrate for producing a cytoprotective biochemical, bilirubin, whilst HO-2 appears to have also anti-diabetic and anti-obese actions.

SARS-CoV-2 infection can lead to life-threatening clinical manifestations. Patients with cardiovascular disease (CVD) are at higher risk for severe courses of COVID-19. However, strategies to predict the course of SARS-CoV-2 infection in CVD patients at the time of hospital admission are still missing. Here, we investigated whether this prediction is achievable by prospectively analysing the blood immunophenotype of 94 participants, including 20 uninfected and 37 acutely SARS-CoV-2-infected CVD patients and 37 healthy donors, using a 36-colour spectral flow cytometry panel. Unsupervised data analysis revealed little differences between healthy donors and CVD patients, whereas the distribution of the cell populations changed dramatically in SARS-CoV-2-infected CVD patients. The latter had more mature NK cells, activated monocyte subsets, central memory CD4+ T cells, and plasmablasts but fewer dendritic cells, CD16+ monocytes, innate lymphoid cells, and CD8+ T cell subsets. Moreover, we identified an immune signature characterised by mucosal-associated invariant T (MAIT) cells, intermediate effector CD8+ T cells, and natural killer T (NKT) cells that is predictive for CVD patients with a severe course of COVID-19. Thus, intensified immunophenotype analyses can help identify patients at risk of severe COVID-19 at hospital admission, improving clinical outcomes through specific treatment.

Coronavirus disease-2019 (COVID-19) was seen as a respiratory disease, however, an increasing number of reports indicated that the spike protein could also be the cause of the long-term post-infectious conditions known as Long-COVID characterized by a group of unresponsive idiopathic severe neuro, cardio-vascular disorders, including strokes, cardiopathies, neuralgias, fibromyalgia, and Parkinson's like-disease. Different lines of pieces of evidence confirmed that the spike protein that can be found on the surface of the SARS-CoV-2 virus latches onto angiotensin-converting enzyme 2 (ACE2) receptors located on target cells. The RNA genome of coronaviruses, which, has a median length of 29 kb and is the longest among all RNA viruses, is comprised of six to ten open reading frames (ORFs) that are responsible for encoding both the replicase and structural proteins for the virus. Each of the components of the viral genome is packaged into a helical nucleocapsid that is surrounded by a lipid bilayer. The viral envelope of coronaviruses is typically made up of three proteins that include the membrane protein (M), the envelope protein (E), and the spike protein (S). The spike protein not only facilitates the virus entry into healthy cells, which is the first step in infection but also promote profound damage to different organs and tissues leading to severe impairments and long-term disabilities. Here, we discussed the pervasive mechanism that spikes mRNA adopted to alter multipotent and pluripotent stem cell (SCs) genomes and the acquired disability of generating an infinite number of affected clonal cells. This stance is based on the molecular and evolutionary aspects obtained from retrotransposons-retrotransposition in mammalians and humans that documented the frequent integration of mRNA molecules into genomes and thus into DNA. Retrotransposition is the molecular process in which transcribed and spliced mRNAs are accidentally reverse-transcribed and inserted into new genomic positions to form a retrogene. Sequence-specific traits of mRNA clearly showed long interspersed element-1 (LINE-1 or L1) to confirm the retrotransposition, considered the most abundant autonomously active retrotransposons in the human genome. In mammals, L1 retrotransposons drive retrotransposition and are composed of long terminal repeats (LTRs) and non-LTR retrotransposons (mainly long interspersed nuclear elements or LINEs); specifically, the LTR-mediated retrocopies are immediately cotranscribed with their flanking LTR retrotransposons. In response to retrotransposons transposition, stem cells (SCs) employ a number of silencing mechanisms, such as DNA methylation and histone modification. This manuscript theorizes the expression patterns, functions, and regulation of mRNA Spike protein imprinted by SCs retrotransposons which generate unlimited lines of affected cell progenies and tissues as the main condition of untreatable Spike-related inflammatory conditions.

Gene or genome editing (GE) revises, removes, or replaces a mutated gene at the DNA level; it is a tool. Gene therapy (GT) offsets mutations by introducing a "normal" version of the gene into the body while the diseased gene remains in the genome; it is a medicine. So far, no in vivo GE product has been approved, as opposed to 22 GT products approved by the FDA. However, several are under development, and the FDA anticipates their fast entry, as evidenced by the FDA's actions of issuing GE-specific guidelines. The potential of GE in treating diseases far supersedes any other modality due to the recognized role of genes in most human diseases. While GT products add missing genes, GE tools can overcome many aberrations. However, GE presents many safety challenges, including off-target impact, delivery consistency, and long-term effects of gene-fixing. However, most of these concerns will be resolved once the FDA begins approving them, leading to hundreds of products capable of treating untreatable diseases.

Cancer patients may experience significant distress. The “Emotion Thermometers” (ETs) are a short visual analogue scale used to screen patients for psychosocial risk. This study aimed to assess emotional distress in a large sample of cancer patients attending psychological services at an NGO, and to explore factors that may contribute to it. The ETs were answered by 899 cancer patients. They were, on average, 59.9 years old, the majority were female, had breast cancer, were under treatment or were disease-free survivors, and reported high levels of emotional distress, above the cut-off (≥5). A Generalized Linear Model was used to measure the association between the level of Distress and 33 items of the problem list. Four items - sadness, depression, sleep and breathing - were found to be significantly related to a higher level of Distress. Additionally, women and those who were in the palliative phase also had significantly higher levels of Distress. Conclusions: The results confirm the need for early emotional screening in cancer patients, as well as the relevance of attending to the characteristics of each patient. Additionally, they highlight the utility of the ETs for the clinical practice, allowing to optimize the referral to specialized psy-chosocial services.

Steroid-responsive meningitis-arteritis (SRMA) is a predominantly Th-2 immune-mediated dis-ease, but exact pathomechanism remains still unclear. Interleukin-31 (IL-31) is predominantly produced by T cells with a Th-2 phenotype during proinflammatory conditions. We hypothesize, IL-31 might be involved in the pathogenesis of SRMA. IL-31 was measured in archived samples (49 serum and 52 CSF samples) of dogs with SRMA, Meningoencephalitis of unknown origin (MUO), infectious meningoencephalitis, atopic dermatitis and of healthy control dogs using a competitive canine IL-31 ELISA. Mean serum IL-31 level in dogs with SRMA (n=18) was mildly higher compared to dogs with atopic dermatitis (n=3) and MUO (n=15) and markedly higher than in healthy controls (n=10) and dogs with infectious meningoencephalitis (n=3). Dogs with SRMA in the acute stage of the disease and without any pre-treatment had the highest IL-31 levels. The mean CSF IL-31 value of dogs with SRMA (n=23) was quite similar to healthy controls (n=8) and did not differ significantly from dogs with MUO (n=19) and infectious meningoencephalitis (n=2). Based on this study, an involvement of IL-31 in the pathogenesis of the systemic Th-2 im-mune-mediated immune response in SRMA can be assumed as a further component leading to an aberrant immune reaction.

Metabolic-associated fatty liver disease (MAFLD) and its potential impact on the severity of COVID-19 have gained significant attention during the pandemic. This review aimed to explore the genetic determinants associated with MAFLD, previously recognized as non-alcoholic fatty liver disease (NAFLD), and their potential influence on COVID-19 outcomes. Various genetic polymorphisms, including PNPLA3 (rs738409), GCKR (rs780094), TM6SF2 (rs58542926), and LYPLAL1 (rs12137855), have been investigated in relation to MAFLD susceptibility and progression. Genome-wide association studies and meta-analyses have revealed associations between these genetic variants and MAFLD risk, as well as their effects on lipid metabolism, glucose regulation, and liver function. Furthermore, emerging evidence suggests a possible connection between these MAFLD-associated polymorphisms and the severity of COVID-19. Studies exploring the association between indicated genetic variants and COVID-19 outcomes have shown conflicting results. Some studies observed a potential protective effect of certain variants against severe COVID-19, while others reported no significant associations. This review highlights the importance of understanding the genetic determinants of MAFLD and its potential implications for COVID-19 outcomes. Further research is needed to elucidate the precise mechanisms linking these genetic variants to disease severity and to develop gene profiling tools for early prediction of COVID-19 outcomes. If confirmed as determinants of disease severity, these genetic polymorphisms could aid in identifying high-risk individuals and improving the management of COVID-19.

The objective of the present study is to analyze COVID-19 transmission in specific dampest regions with excess rainfall and recurring fogs. The working hypothesis is that widespread transmission of SARS CoV 2 (leading to COVID-19) and similar viral agents can be explained by specific climate factors having high air humidity. The main case study of the Turkish Black Sea region is investigated. Results reveal that the provinces in region under study have some climate factors and geographical features that foster the accelerated transmission of viral agents, such as SARS-CoV-2, and consequential negative impact on society. In particular, Spearman's Correlation Coefficient shows a statistically significant positive association between the average atmospheric pressure and the spread of the COVID-19 confirmed cases in Samsun province (Spearman’s correlation coefficient rs =0.86, p-value 0.05). A statistically significant positive association between the average precipitation and the spread of COVID-19 confirmed cases in Sinop province (Spearman’s correlation coefficient rs =0.79, p-value 0.05), and finally, a statistically significant negative association between the average sun hour and the spread of the COVID-19 confirmed cases in Samsun province (Spearman’s correlation coefficient rs = 0.89, p-value 0.01). These findings suggest that regions' geographical characteristics, demographic structure, climate and environmental parameters must be considered in the national scale epidemic management plans to design effective anti-pandemic health policies to cope with future waves of the COVID-19 and new airborne diseases and to reduce negative effects on health, social and economic systems.

As the name implies, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-stranded RNA virus and a member of the corona virus family, primarily affecting the upper respiratory system and the lungs. Like many other respiratory viruses, SARS-CoV-2 can spread to other organ systems. Apart from causing diarrhea, another most common but debilitating complication caused by the SARS-CoV-2 is neurological symptoms and cognitive difficulties, which occur in up to two thirds of hospitalized covid patients and ranging from shortness of concentration, overall declined cognitive speed to executive or memory function impairment. Neuro-cognitive dysfunction and “brain fog” are frequently present in COVID-19 cases, which can last several months after the infection, leading to disruption of daily life. Cumulative evidence suggests that SARS-CoV-2 affects vasculature in the extra pulmonary systems directly or indirectly, leading to impairment of endothelial function and even multi-organ damage. The post COVID-19 long-lasting neurocognitive impairments have not been studied fully; and the underlying mechanism remains elusive. In this review, we summarize the current understanding of the effects of COVID-19 on vascular dysfunction and how vascular dysfunction leads to cognitive impairment in patients.

Synthetic antivirals and corticosteroids have been used to treat both influenza and the SARS-CoV-2 disease named COVID-19. However, these medications are not always effective, produce several adverse effects, and are associated with high costs. Medicinal plants and their constituents act in several different targets and signaling pathways involved in the pathophysiology of Influenza and COVID-19. This study aimed to perform a review to evaluate the effects of medicinal plants on Influenza and COVID-19 and to investigate the potential delivery systems for new antiviral therapies. EMBASE, PubMed, GOOGLE SCHOLAR, and COCHRANE databases were searched. The studies included in this review showed that medicinal plants, in different formulations, can help decrease viral spread and time of full recovery. Plants reduced the incidence of acute respiratory syndromes and the symptom scores of the illnesses. Moreover, plants are related to few adverse effects and have low costs. In addition to their significance as natural antiviral agents, medicinal plants and their bioactive compounds may exhibit low bioavailability. This highlights the need for alternative delivery systems, such as metal nanoparticles, that can effectively transport these compounds to infected tissues.

In this review, we aimed to understand the relationship between SARS-CoV-2 infection and preeclampsia severity in infected pregnant women. Pregnant women with SARS- CoV-2 infection have been shown to have a significantly increased risk of maternal death, ICU admission, preterm delivery, and stillbirth compared with those without infection. The risk of preeclampsia also increases in pregnant women infected with SARS-CoV-2, particularly in those with severe symptoms. We emphasize the im-portance of specialized clinical management to prevent poor pregnancy outcomes in this situation. The association between COVID-19 and preeclampsia (PE) is likely due to multiple mechanisms, including the direct effects of the virus on trophoblast function and the arterial wall, acute atherosis, local inflammation leading to pla-cental ischemia, exaggerated inflammatory responses in pregnant women, SARS-CoV-2-related myocardial injury, cytokine storm, and thrombotic microan-giopathy. Emphasis has been placed on the potential impact of COVID-19 on pregnant women, specifically in relation to thrombotic complications, placental dysfunction, and cardiovascular dysfunction. Undoubtedly, one of the diagnostic tools to differentiate between COVID-19-induced preeclampsia-like syndrome and true preeclampsia is the use of biomarkers, such as the sFlt-1/PlGF ratio. We wish to highlight the potential for COVID-19-induced myocardial injury in pregnant women and the associated in-crease in maternal mortality rate. Vaccination against COVID-19 in the general population and in pregnant women in particular, drastically reduced the severity of the disease. There is an urgent need to continue the follow-up of these women and their children to detect the appearance of sequelae of the disease or peristent COVID 19

Aim: Aging is companied by deteriorations of insulin resistance (IR) and insulin secretion. However, little is known about the roles of aging on different phases of insulin secretion (ISEC); i.e., the first- and second-phase of insulin secretion (FPIS, SPIS) and glucose effectiveness (GE). Methods: Totally 169 individuals (43 men and 126 women) with the similar fasting plasma glucose (FPG: 90 mg/dL) and BMI (men: 23 kg/m2, women 22 kg/m2) were enrolled. IR, FPIS, SPIS, and GE were estimated using our previously developed equations shown below. Pearson correlation analysis was conducted to assess the correlations between age and four diabetes factors (DFs: IR, FPIS, SPIS and GE). The equations that are used to calculate the DF in the present study were built and published by our group. Results: The age of the participants ranged from 18- to 78-year-old. Men had higher FPIS but lower HDL-C levels than women (2.067±0.159, 1.950±0.186 μU/min and 1.130±0.306, 1.348±0.357 mmol/dl, accordingly). The results of Pearson correlation revealed that age was negatively related to IR and GE in both genders (IR: r = -0.39, p < 0.001 for men, r = -0.24, p < 0.003 for women; GE: r = 0.66, p < 0.001 for men, r = 0.78, p < 0.001 for women). In the meanwhile, FPIS was also only found to be negatively correlated with age in female (r = -0.238, p = 0.003). But there was no different with SPIS and age in both of genders. Conclusions: We have found that in Chinese with normal FPG level (90 mg/dl) and body mass index (men: 23 kg/m2, women: 22: kg/m2), age is negatively related to IR and GE in both genders. At the same time, only FPIS was found to be negatively related to age in women. The tightness of their relationships, from the highest to the lowest are, GE, FPIS and IR accordingly. The importance of GE should be re-evaluated. These results should be interpreted with caution because of the small sample size.

This paper presents the symmetries of differential equations associated with one-variable and Bivariate Hermite polynomials by proposing a representation of Lie algebra for these differential operators. Applying the Baker-Campbell-Hausdorff formula to these algebras, results in new relations and generating functions in one-variable and Bivariate Hermite polynomials. A general form of representation for other orthogonal polynomials such as Laguerre polynomials is introduced.

Background Hydroxychloroquine (HCQ) combined with azithromycin (AZM) has been widely administered to patients with COVID-19 despite scientific controversies. In particular the potential to prolong cardiac repolarisation by using this combination has been discussed. Materials and methods We report a pragmatic and simple safety approach which we implemented in the first patients treated for COVID-19 in our center early 2020. Treatment contraindications were the presence of severe structural or electrical heart disease, baseline corrected QT interval (QTc) >500 ms, hypokalaemia, or other drugs prolonging QTc that could not be interrupted. Electrocardiogram and QTc was evaluated at admission and re-evaluated after 48 hours of the initial prescription. Results Among 424 consecutive adults (mean age 46.3 ± 16.1 years; 216 women). Patients were followed in conventional wards (21.5%) or in a day-care unit (78.5%). A total of 11 patients (2.6%) had contraindications to HCQ-AZ combination. In the remaining 413 treated patients, there were no arrhythmic events in any patient during the 10-day treatment regimen. QTc was slightly but statistically significantly prolonged by 3.75 ± 25.4 ms after two days (p=0.003). Ten patients (2.4%) developed QTc prolongation >60 ms, and none had QTc >500 ms. Conclusions This report do not aim to contribute to knowledge of the efficacy of treating COVID-19 with HCQ-AZ. However, a simple initial assessment of patient medical history, ECG and kalaemia identifies contraindicated patients and enables the safe treatment by HCQ-AZ of COVID-19 patients. QT-prolonging anti-infective drugs can be used safely in acute life-threatening infections, provided that a strict protocol and close collaboration between infectious disease specialists and rhythmologists are followed.

Due to the fact that to date, the question of the origin of SARS-CoV-2 has not been resolved yet, the author analyzed the main advances in the development of genetic engineering of viruses that took place before the onset of the COVID-19 pandemic. The first artificial genetically modified viruses could appear in nature in the mid-1950s. The technique of nucleic acid hybridization was developed by the end-1960s. In the late 1970s, a method called the "reverse genetics" emerged to synthesize RNA and DNA molecules. In the early 1980-s, it became possible to combine the genes of different viruses and insert the genes of one virus into the genome of another virus. Since that time, the production of vector vaccines began. Currently, by modern technologies one can assemble any virus based on the nucleotide sequence available in the virus database or designed by a computer as a virtual model.Scientists around the world are invited to answer the call of Neil Harrison and Jeffrey Sachs of Columbia University, for a thorough and independent investigation into the origin of SARS-CoV-2. Only a full understanding of the origin of the new virus can minimize the likelihood of a similar pandemic in the future.

The article is devoted to the problem of autoimmune diseases provocation by coronavirus infection and the role of molecular mimicry in this phenomenon. SARS-CoV-2 can disguise its proteins as human ones in order to avoid immune attack. A bioinformatics analysis of the probable pentapeptide sharing between human autoantigens of endocrinocytes and SARS-CoV-2 spike protein, membrane protein and nucleocapsid protein was performed. Antigen mimicry between S-proteins of all other known human Coronaviruses and typical target autoantigens of endocrinocytes was also explored. Six human-identical regions were found in the SARS-CoV-2 membrane and nucleocapsid proteins, all of them in their immunodominant epitopes. All shared epitopes belong to antigens of endocrine cells commonly targeted during autoimmune endocrinopathies. Moreover, samples of the pituitary, adrenal and thyroid from patients who died from coronovirus infection (COVID-19) were studied morphologically using histochemical methods. A high frequency of SARS-CoV-2 caused inflammation of the studied endocrine organs was found in patients who died from severe COVID-19. At the same time, the abundant expression of virus antigens by the cells of the adenohypophysis was combined with the complete absence of its expression by the cells of the neurohypophysis. SARS-CoV-2 infected cells apparently perished by non-apoptotic pathway. The foci of lesions in endocrine organs contained abundant lymphocytic infiltrates which may witness for the impact of autoimmune processes. The facts revealed emphasize the need of endocrinological diagnostic alertness of a physician while observing patients with post-vaccination and post-COVID-19 health disorders. [3 figures, 6 tables, bibliography: 45 references].

Abstract: The SARS-CoV-2 pandemic has reemphasized the urgent need for broad-spectrum antiviral therapies. We developed a computational workflow using scRNA-Seq data to assess cellular metabolism during viral infection. With this workflow we predicted the capacity of cells to sustain SARS-CoV-2 virion production in patients and found a tissue-wide induction of metabolic pathways that support viral replication. Expanding our analysis to influenza A and dengue viruses, we identified metabolic targets and inhibitors for potential broad-45 spectrum antiviral treatment. These targets were highly enriched for known interaction partners of all analyzed viruses. Indeed, phenformin, an NADH:ubiquinone oxidoreductase inhibitor, suppressed SARS-CoV-2 and dengue virus replication. Atpenin A5, blocking succinate dehydrogenase, inhibited SARS-CoV-2, dengue virus, respiratory syncytial virus, and influenza A with high selectivity indices. In vivo, phenformin showed antiviral activity against SARS-CoV-2 in a Syrian hamster model. Our work establishes host metabolism as druggable for broad-spectrum antiviral strategies, providing invaluable tools for pandemic preparedness.

High circulating concentrations of the gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) are significantly associated with the risk of obesity and type 2 diabetes (T2D). We aimed at evaluating the impact of glycemic control and bariatric surgery on circulating concentrations of TMAO and its microbiota-dependent intermediate, γ-butyrobetaine (γBB), in newly diagnosed T2D patients and morbidly obese subjects. An additional experiment was carried out in eight male C57BL/6J mice fed a Western-type diet for twelve weeks. The strategy for glycemic control in the T2D patients significantly improved the HbA1c concentrations without producing changes in the estimated glomerular filtration rate. However, the plasma TMAO and γBB concentrations were significantly increased following the glycemic control in T2D patients. Bariatric surgery was very effective in reducing weight in obese subjects. Nevertheless, the surgery reduced plasma γBB concentrations without affecting TMAO concentrations and the estimated glomerular filtration rate. Neither diet-induced obesity nor insulin resistance were associated with circulating TMAO and γBB concentrations in mice. Our findings do not support that glycemic control or bariatric surgery improve the circulating concentrations of TMAO in newly diagnosed T2D and morbidly obese patients. The contribution of antidiabetic drugs to gut microbiota composition could explain TMAO elevations in treated T2D subjects.

Interferometry Synthetic Aperture Radar (InSAR) is an advanced remote sensing technique for studying the earth's surface topography and deformations. It is used to generate high-quality Digital Elevation Models (DEMs). DEMs are a crucial and primary input to various topographical quantification and modelling applications. The quality of input DEMs can be further improved using fusion methods, which combine multi-sensor or multi-temporal datasets intelligently to retrieve the best information amongst the input data. This research study is based on developing a Neural Network based fusion approach for improving InSAR based DEMs in plain and hilly terrains. The study areas comprise of relatively plain terrain from Ghaziabad and hilly terrain of Dehradun and their surrounding regions. The training dataset consists of DEM elevations and derived topographic attributes like slope, aspect, topographic position index (TPI), terrain ruggedness index (TRI), and vector roughness measure (VRM) in different land use land cover classes of the study areas. The spaceborne altimetry ICESat-2 ATL08 photon data is used as a reference elevation. A Feed Forward Neural Network with backpropagation algorithm is trained based on the prepared training samples. The trained model produces fused DEMs by learning the relationship between the input and target samples. This is used to predict elevations in the test areas. The accuracy of results from the models are assessed with TanDEM-X 90 m DEM. The fused DEMs show significant improvement in terms of RMSE over the input DEMs with improvement factor of 94.65 % in plain area and 82.62 % in hilly area. The study concludes that the ANN with its universal approximation property is able to significantly improve the fused DEM.

This was a retrospective cohort study, which aimed to investigate the factors associated with hesitancy to receive the third dose of coronavirus disease 2019 (COVID-19) vaccine. A paper-based questionnaire survey was administered to all participants. Accordingly, the study included participants who provided answer in the questionnaire whether they have an intent to receive the third dose of vaccine. Data on sex, age, area of residence, adverse reactions after the second vaccination, whether the third vaccination was desired, and reasons to accept or hesitate booster vaccination were retrieved. Among the 2439 participants with mean (±SD) age of 52.6±18.9 years, and median IgG-S antibody titer of 324.9 (AU/mL), 97.9% of participants indicated their intent to accept a third vaccination dose. The logistic regression revealed that younger age (OR=0.98; 95% CI: 0.96-1.00) and higher antibody level (OR=2.52; 95% CI: 1.27-4.99) are positively associated with the third vaccine hesitancy. The efficacy of the COVID-19 vaccine and concerns about adverse reactions had significant impact on the third vaccination behavior. A rapid increase in the booster dose rate is needed to control the pandemic, and specific approaches should be taken in these groups that are likely to hesitate the third vaccine, subsequently increasing booster contact rate.

The 2019 Coronavirus Disease (COVID-19) is a major cause of morbidity and mortality worldwide. Since late November 2021, Omicron variant has emerged as the primary cause of COVID-19 and caused a huge increase in the reported incidence around the world. To date, 32-34 spike mutations have been reported, 15 of which were located in the receptor-binding domain that interacts with the cell surface of the host cells, while the rest were located in the N-terminal domain and around the Furin cleavage site. At present, both the genomic and clinical profiles of this novel variant are being investigated. Here, we aim to discuss the recent reports on the transmissibility and severity of Omicron variant from both the genetic and clinical perspectives. Afterward, we also take the chance to deliver our personal view on the topic.

Individuals from rural areas are increasingly using social media as a means of communication, receiving information, or actively complaining of inequalities and injustices. This study captured 57 days’ worth of Twitter data from June to August 2021 related to rural health using English language keywords. The study utilised social network analysis and natural language processing to analyse the data. It was found that Twitter served as a fruitful platform to raise awareness of problems faced by those living in rural areas. Overall, Twitter was utilised in rural areas to express complaints, to debate, and share information. Twitter could be leveraged as a powerful social listening tool for individuals and organisations who want to gain insight into popular narratives around rural health.

A national green planning strategy has recently been introduced in the Italian urban planning sector, aimed at making all local initiatives undertaken nationwide consistent with each other. At a regional level, Friuli Venezia-Giulia has recently implemented a Landscaping Plan, which is of an urban planning and ecological nature at an intermediate level between national and local. This article describes the local green plan of Latisana, which has been entitled Ecopolitana, given that it is represents the experimental phase, at a regional level, of the possibilities offered by landscape planning and design. Specifically, it outlines the multi-disciplinary approach used, demonstrating how landscape planning can be compared to the sustainable development of cities, with specific regard to the agricultural sector. Regarding the agricultural sector, a low-intensity cropping model is also suggested, based on the principles of agroecology and landscape ecology, which has already been implemented in the historical rural landscape of Plasencis (UD) and developed through GIS analysis and remote sensing processes. Its aim is to be the starting point for the achievement of the goals set in the 2030 Agenda, and especially Goals 13 (Climate action) and 15 (Life on land), given the current scarcity of agroecological infrastructures in the area of Latisana (UD) and the high percentage of soil used for intensive cropping.

The characteristic lesion of primary tuberculosis is the granuloma as is widely studied in human tissues and animal models. Post-primary tuberculosis is different. It develops only in human lungs and begins as a prolonged subclinical obstructive lobular pneumonia that slowly accumulates mycobacterial antigens and host lipids in alveolar macrophages with nearby highly sensitized T cells. After several months, the lesions undergo necrosis to produce a mass of caseous pneumonia large enough to fragment and be coughed out to produce a cavity or be retained as the focus of a post-primary granuloma. Here we extend these findings with the demonstration of mycobacterial antigen, but not AFB, of M. tuberculosis in the cytoplasm of ciliated bronchiolar epithelium and alveolar pneumocytes in association with elements of the programmed death ligand 1 (PD-L1), cyclo-oxygenase (COX)-2, and fatty acid synthase (FAS) pathways in the early lesion. This suggests that M. tuberculosis uses its secreted antigens to coordinate prolonged subclinical development of the early le-sions in preparation for a necrotizing reaction sufficient to produce a cavity, post-primary granulomas and fibrocaseous disease.

The characteristic lesion of primary tuberculosis is the granuloma as is widely studied in human tissues and animal models. Post-primary tuberculosis is different. It develops only in human lungs and begins as a prolonged subclinical obstructive lobular pneumonia that slowly accumulates mycobacterial antigens and host lipids in alveolar macrophages with nearby highly sensitized T cells. After several months, the lesions under necrosis to produce a mass of caseous pneumonia large enough to fragment and be coughed out to produce a cavity or be retained as the focus of a post-primary granuloma. Here we extend these findings with the demonstration of mycobacterial antigen, but not AFB, of M. tuberculosis in the cytoplasm of ciliated bronchiolar epithelium and alveolar pneumocytes in association with elements of the programmed death ligand 1 (PD-L1), cyclo-oxygenase (COX)-2, and fatty acid synthase (FAS) pathways in the early lesion. This suggests that M. tuberculosis use its secreted antigens to coordinate prolonged subclinical development of the early lesions in preparation for a necrotizing reaction sufficient to produce a cavity, post-primary granulomas and fibrocaseous disease

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic systemic inflammation causing progressive joint damage that can lead to lifelong disability. The pathogenesis of RA involves a complex network of various cytokines and cells that trigger synovial cell proliferation and cause damage to both cartilage and bone. Involvement of the cytokines TNF- and IL-6 is central to the pathogenesis of RA, but recent research has revealed that other cytokines such as IL-17, IL-23, GM-CSF, IL-33, and IL-2 also play a role. Clarification of RA pathology has led to the development of therapeutic agents such as biological disease-modifying anti-rheumatic drugs (DMARDs) and Janus kinase (JAK) inhibitors, and further details of the immunological background to RA are emerging. This review covers existing knowledge regarding the roles of cytokines, related immune cells and the immune system in RA, manipulation of which may offer the potential for even safer and more effective treatments in the future.

Various products of the Integrated Multisatellite Retrievals for GPM (IMERG) and passive mi-crowave (PMW) sensors are assessed with respect to near-surface wet-bulb temperature (Tw), precipitation intensity, and surface type (i.e., with and without snow and ice on the surface) over the CONUS and using Stage-IV product as reference precipitation. IMERG products include precipitation estimates from infrared (IR), combined PMW, and their combination. PMW products generally have higher skills than IR over snow- and ice-free surfaces. Over snow- and ice-covered surfaces (1) PMW products (except AMSR-2) show a higher correlation coefficient than IR, (2) IR and PMW precipitation products tend to overestimate precipitation, but at colder temperatures (e.g., Tw<-10oC) PMW products tend to underestimate and IR product continues to show large overestimations, and (3) PMW sensors show higher overall skill in detecting precipitation oc-currence, but not necessarily at very cold Tw. The results suggest that the current approach of IMERG (i.e., replacing PMW with IR precipitation estimates over snow- and ice-surfaces) may need to be revised.

The COVID-19 pandemic has had devastating consequences for health, social, and economic domains, but what has received far less focus is the effect on people’s relationship to vital ecological supports, including access to greenspace. We assessed patterns of greenspace use in relation to individual and environmental factors and their relationship with experiencing psychological symptoms under the pandemic. We conducted an online survey recruiting participants from social media for adults in Korea for September–December 2020. The survey collected data on demographics, patterns of using greenspace during the pandemic, and major depression (MD) and generalized anxiety disorder (GAD) symptoms. The Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder 2-item (GAD-2) were applied to identify probable cases of MD and GAD. A logistic regression model assessed the association decreased visits to greenspace after the outbreak compared to 2019 and probable MD and GAD. Among the 322 survey participants, prevalence of probable MD and GAD were 19.3% and 14.9%, respectively. High rates of probable MD (23.3%) and GAD (19.4%) were found among persons currently having job-related and financial issues. Of the total participants, 64.9% reported decreased visits to greenspace after the COVID-19 outbreak. Persons with decreased visits to greenspace had 2.06 higher odds (95% CI: 0.91, 4.67) of probable MD at the time of the survey than persons whose visits to greenspace increased or did not change. Findings suggest that barriers to greenspace use could deprive people of mental health benefits and affect mental health during pandemic; an alternative explanation is that those experiencing poor mental health may be less likely to visit greenspaces during pandemic. This implies the need of adequate interventions on greenspace uses under an outbreak especially focusing on how low-income populations may be more adversely affected by a pandemic and its policy responses.

To reduce the risk of infection of SARS-CoV-2 during the commute to the clinic or due to the contact with medical staff, The American College of Obstetricians and Gynecologists recommended ar-ranging part of the appointments in the form of “telehealth”. The aim of the study was to assess the access to medical care in pregnancy during the Sars-Cov-2 pandemic and the role of telehealth in implementation of prenatal care standards. This is a cross-sectional study. The study group in-cluded 618 women that were pregnant and or gave birth during the COVID-19 pandemic in Poland. The majority of participants experienced difficulties in access to medical care because of the pandemic. Correlation between this experience and the use of hybrid healthcare model was es-tablished. However, affiliation to public or private healthcare group was irrelevant. There was no relationship between healthcare (private/public or in-person/hybrid) and implementation of the prenatal care standards. To ensure safe access to prenatal care for pregnant women, recommen-dations for a hybrid pregnancy management model should be created with detailed information for which appointments patients must be present and which can be done remotely. To reduce movement risk and interpersonal contact, all visits during which tests and screenings take place should be done in-person. Other appointments can be arranged in the form of telehealth

The musculoskeletal system consisting of bones and muscles have been recognized as endocrine organs secreting hormones that are involved in regulating metabolic and inflammatory pathways. Obesity and type 2 diabetes (T2D) are associated with several musculoskeletal system complications. We hypothesized that an interaction exists between adipomyokines namely, irisin and METRNL, and various bone markers in individuals with obesity and T2D. A total of 228 individuals were enrolled in this study, including 124 non-diabetic and 104 T2D. A Multiplex assay was used to assess the level of various bone markers namely Osteoactivin, Syndecan, osteoprotegerin (OPG) and osteonectin/SPARC. Our data shows elevated levels of Osteoactivin, Syndecan, OPG and SPARC in T2D as compared to non-T2D individuals (p ≤ 0.05). Using Spearman’s correlation, irisin was positively correlated only with Osteoactivin and OPG (p &lt; 0.05). Similarly, a positive association was observed between METRNL and Osteoactivin (p &lt; 0.05). The strong positive association shown in our study between irisin, METRNL and various bone markers emphasises the strong interaction between these organs. This suggests that a dysregulation in the functional interaction between these molecules could play a possible role in the development of bone and muscle related complications that are associated with obesity and T2D.

We live in the time of profound transformations commonly labelled with the word “globalization”. The rise of one ecological-technological-social system encompassing our whole planet is an important element of these processes. Solving big global problems demands knowledge of two complementary sorts: on the one hand – going “in depth”, on the other – going “in breadth”. The present paper assumes the second (in a sense: philosophical) perspective. It tries to analyze some relations between the development of technology (IT) and the development of democracy. The notion of democracy, its various forms and axiological reasons for it are considered first. In the subsequent chapter different consequences (both positive and negative) the IT development has for contemporary democracy are discussed. In the next chapter the evolutionary nature of the technological development is debated as well as the question of (democratic) control of this process. The development of Artificial General Intelligence is presented as a challenge for democracy

Inhibition of the binding of enveloped viruses surface glycoproteins to host cell receptor(s) is a major target of vaccines and constitutes an efficient strategy to block viral entry and infection of various host cells and tissues. Cellular entry usually requires fusion of the viral envelope with host plasma membranes. Such entry mechanism is often preceded by “priming” and/or “activation” steps requiring limited proteolysis of the viral surface glycoprotein to expose a fusiogenic domain for efficient membrane juxtapositions. The 9-membered family of Proprotein Convertases related to Subtilisin/Kexin (PCSK) serine proteases (PC1, PC2, Furin, PC4, PC5, PACE4, PC7, SKI-1/S1P and PCSK9) participate in post-translational cleavages and/or regulation of multiple secretory proteins. The type-I membrane-bound Furin and SKI-1/S1P are the major convertases responsible for the processing of surface glycoproteins of enveloped viruses. Stefan Kunz has considerably contributed to define the role of SKI-1/S1P in the activation of arenaviruses causing hemorrhagic fever. Furin was recently implicated in the activation of the spike S-protein of SARS-CoV-2 and Furin-inhibitors are being tested as antivirals in COVID-19. Other members of the PCSK-family are also implicated in some viral infections such as PCSK9 in Dengue. Herein, we summarize the various functions of the PCSKs and present arguments whereby their inhibition could represent a powerful arsenal to limit viral infections causing the present and future pandemics.

The COVID-19 pandemic has become a public health emergency of international concern, which may affect lifestyle habits and mental health. Based on national health profile assessments, this study investigates perceived changes of lifestyle habits in response to the COVID-19 pandemic and associations between perceived lifestyle changes and mental health in Swedish working adults. Among 5,599 individuals (50% women, 46.3 years), the majority reported no change (sitting 77%, daily physical activity 71%, exercise 69%, diet 87%, alcohol 90%, and smoking 97%) due to the pandemic. Changes were more pronounced during the first wave (April-June) compared to the second (October-December). Women, individuals <60 years, having a university degree, being white-collar workers and having unhealthy lifestyle habits at baseline had higher odds of changing lifestyle habits compared to their counterparts. Negative changes in lifestyle habits as well as more time in mentally passive sitting at home was associated with higher odds of mental ill-health (including health anxiety regarding one’s own and relatives’ health, generalized anxiety and depression symptoms, and concerns regarding employment and economy). The results em-phasize the need to support healthy lifestyle habits to strengthen the resilience in vulnerable groups of individuals to future viral pandemics, and prevent health inequalities in society.

COVID-19 breakout calls for immediate research explorations. The objective of this study is to perform a bibliometric analysis of all COVID-19-related publications in Science Citation Index Expanded (SCI-EXPANDED) in the early stage of the outbreak. Analysis parameters include performances of authors, institutes, and countries as well as distributions of Web of Science categories, journals, languages, and types of publications. Results show that 32% of total papers were published as editorial materials and an overwhelming production from Chinese research institutes. An association of research indexes with the number of cases was also found.

With the COVID-19 pandemic now ongoing for close to a year, people all over the world are still waiting for a vaccine to become available. The initial focus of accelerated global research and development efforts to bring a vaccine to market as soon as possible was on novel platform technologies that promised speed but had limited history in the clinic. In contrast, recombinant protein vaccines, with numerous examples in the clinic for many years, missed out on the early wave of investments from government and industry. Emerging data are now surfacing suggesting that recombinant protein vaccines indeed might offer an advantage or complement to the nucleic acid or viral vector vaccines that will likely reach the clinic faster. Here, we summarize the current public information on the nature and on the development status of recombinant subunit antigens and adjuvants targeting SARS-CoV-2 infections.

The ongoing global pandemic caused by coronavirus disease 2019 (COVID-19) has once again demonstrated the significance of the Coronaviridae family in causing human disease outbreaks. As SARS-CoV-2 was first detected in December 2019, information on its tropism, host range, and clinical presentation in animals is limited. Given the limited information, data from other coronaviruses may be useful to inform scientific inquiry, risk assessment and decision-making. We review the endemic and emerging alpha- and betacoronavirus infections of wildlife, livestock, and companion animals, and provide information on the receptor usage, known hosts, and clinical signs associated with each host for 15 coronaviruses discovered in people and animals. This information can be used to guide implementation of a One Health approach that involves human health, animal health, environmental, and other relevant partners in developing strategies for preparedness, response, and control to current and future coronavirus disease threats.