A novel and highly pathogenic coronavirus (2019-nCoV)-induced pneumonia spread worldwide in a short time. However, studies on the effects of 2019-nCoV on the male reproductive system are limited. The aim of this study is to describe the clinical characteristics of the male reproductive system of COVID-19 patients and to explore the presence of 2019-nCoV in semen. Retrospective, single-center case series of 112 male patients with confirmed COVID-19 who were admitted to Renmin Hospital of Wuhan University from January 2 to March 7, 2020. Demographic data, symptoms and signs related to the male reproductive system, throat swabs and semen samples were collected and analyzed. 2019-nCoV RNA measured in throat swab and semen samples. The organ distribution of ACE2 mRNA and protein in human tissue on The Human Protein Atlas portal and investigated immunohistochemistry (IHC) images of the testis. The HPA dataset revealed relatively high levels of ACE2 protein and RNA expression in the testis. A total of 3 severe COVID-19 patients (2.7%) presented with orchidoptosis, while no patients experienced other symptoms or signs related to the male reproductive system. The analysis of 2019-nCoV RNA in semen included 17 patients with fertility needs. Among these patients, 9 (52.9%) remained positive for 2019-nCoV according to throat swab analysis, and 8 (47.1%) became negative. In the semen 2019-nCoV analysis, all 17 patients were negative for the N gene and ORF1ab gene. In view of the potential impairment, long-term follow-up for male COVID-19 patients with fertility needs is of great significance.

Objectives: This study aims to identify, report, and analyze registered and published clinical trials and observational studies for the pharmacological treatment of COVID-19 conducted in China. Methods: A strategic search was conducted via the Chinese Clinical Trial Registry to identify and extract clinical trials and observational studies registered and conducted in China for the pharmacological treatment of COVID-2019 between January 1^st, 2020 and March 21^st, 2020. This was further supplemented by searches conducted via the China National Knowledge Infrastructure (CNKI) database, the MEDLINE database, the World Health Organization (WHO) database, and MedRxiv and BioRxiv electronic platforms for preprint articles, published up until April 8^th, 2020. Studies available in Chinese and English were included in the searches and extracted. A primary descriptive analysis was performed for registered clinical trials and observational studies identified in the Chinese Clinical Trial Registry based on the extraction of the following clinical study information: trial ID, planned date of enrollment, recruitment status, study design, population, sample size, intervention/exposure group, control /reference group, dosage, and primary outcomes. A secondary descriptive analysis was performed for published clinical trials and observational studies identified from the supplementary databases based on the extraction of the following published clinical study information: study design, population, intervention/exposure group, control /reference group and main results as appropriate. Results: A total of 221 clinical trials and observational studies were included from all databases searched. From the Chinese Clinical Trial Registry, 195 registered clinical studies including 170 clinical trials and 25 observational studies were identified and included for primary analysis. From the supplementary databases, 26 published clinical studies including 8 clinical trials and 18 observational studies were included for secondary analysis. Of these 26 published clinical studies, 18 studies, including 3 clinical trials and 15 observational studies were identified from CNKI, 2 studies including 1 clinical trial and 1 observational study from MEDLINE, 2 including 1 clinical trials and 1 observational studies from the WHO database, and 4 including 3 clinical trials and 1 observational studies from MedRxiv and BioRxiv platforms. In the primary analysis, among the 170 clinical trials included from the Chinese Clinical Trial Registry, 101 investigated western medicines (WMs), while 15 investigated Traditional Chinese Medicines (TCMs), and 54 investigated a combination of TCMs and WMs. Among the 25 included observational studies from the Chinese Clinical Trial Registry, 2 investigated WMs, 2 investigated TCMs, and 21 investigated a combination of TCMs and WMs. The total number of exposed patients in all 195 clinical studies from the Chinese Clinical Trial Registry amounted to 24,500. In the secondary analysis, treatment with Lopinavir-ritonavir and treatment with Hydroxychloroquine was not associated with a difference from standard of care in the rate of RT-PCR negativity; treatment with a combination of Lopinavir-ritonavir, interferon α, and Lian-Hua-Qing-Wen capsule was found to significantly improve the effective rate of treatment compared with Interferon α combined with Lian-Hua-Qing-Wen capsule. Conclusions: China is generating a massive source of evidence that is critical for defeating the COVID-19 pandemic. Not only the clinical experience, but also the scientific evidence should be shared with the global scientific community.

In the end of December 2019, a new strain of coronavirus was identified in the Wuhan city of Hubei province in China. Within a shorter period of time, an unprecedented outbreak of this strain was witnessed over the entire Wuhan city. This novel coronavirus strain was later officially renamed as COVID-19 (Coronavirus disease 2019) by the World Health Organization. The mode of transmission had been found to be human-to-human contact and hence resulted in a rapid surge across the globe where more than 1,100,000 people have been infected with COVID-19. In the current scenario, finding potent drug candidates for the treatment of COVID-19 has emerged as the most challenging task for clinicians and researchers worldwide. Identification of new drugs and vaccine development may take from a few months to years based on the clinical trial processes. To overcome the several limitations involved in identifying and bringing out potent drug candidates for treating COVID-19, in the present study attempts were made to screen the FDA approved drugs using High Throughput Virtual Screening (HTVS). The COVID-19 main protease (COVID-19 Mpro) was chosen as the drug target for which the FDA approved drugs were initially screened with HTVS. The drug candidates that exhibited favorable docking score, energy and emodel calculations were further taken for performing Induced Fit Docking (IFD) using Schrodinger’s GLIDE. From the flexible docking results, the following four FDA approved drugs Sincalide, Pentagastrin, Ritonavir and Phytonadione were identified. In particular, Sincalide and Pentagastrin can be considered potential key players for the treatment of COVID-19 disease.

With the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that results in coronavirus disease 2019 (COVID-19), corporate entities, federal, state, county and city governments, universities, school districts, places of worship, prisons, health care facilities, assisted living organizations, daycares, homeowners, and other building owners and occupants have an opportunity to reduce the potential for transmission through built environment (BE) mediated pathways. Over the last decade, substantial research into the presence, abundance, diversity, function, and transmission of microbes in the BE has taken place and revealed common pathogen exchange pathways and mechanisms. In this paper, we synthesize this microbiology of the BE research and the known information about SARS-CoV-2 to provide actionable and achievable guidance to BE decision makers, building operators, and all indoor occupants attempting to minimize infectious disease transmission through environmentally mediated pathways. We believe this information is useful to corporate and public administrators and individuals responsible for building operations and environmental services in their decision-making process about the degree and duration of social-distancing measures during viral epidemics and pandemics.

Over the past decade, Knowledge bases (KB) have been increasingly utilized to complete and enrich the representation of queries and documents in order to improve the document retrieval task. Although many approaches have used KB for such purpose, understanding how effectively lev-erage entity-based representation still needs to be resolved. This paper proposes a Purely Enti-ty-based Semantic Search Approach for Information Retrieval (PESS4IR) as a novel solution. The approach includes (i) its own entity linking method, (ii) an inverted indexing method, and for document retrieval and ranking, (iii) an appropriate ranking method is designed to take advantage of all the strengths of the approach. We report the findings on the performance of our approach tested by queries annotated by two known entity linking tools, REL and DBpedia-Spotlight. The experiments are performed on the standard TREC 2004 Robust and MSMARCO collections. By using the REL method, for queries whose all terms are annotated and whose average annotation scores are greater than or equal to 0.75, our approach achieves the maximum nDCG@5 score (1.000). Thus, using our approach with any other document retrieval method would be an added value, unless that method achieves the maximum nDCG@5 score for those highly annotated queries.

Nature-based Solutions (NbS) have rapidly been gaining traction across the research, policy, and practice spheres, touted as transformative actions to jointly address biodiversity loss and climate change. However, there are multiple, alternative ways to imagine NbS in those three spheres. To inform the NbS discourses across these three spheres, we critically reflect on the prevailing framing of NbS and consider the potential of a different framing of NbS to support transformations towards regenerative relationships between humans and nature. Such reflection is urgently needed to ensure that research, policy, and practice delivers on the transformative ambitions of NbS. We propose a novel “core framing” of NbS, charting two pathways for how such a framing can support a human value-based transformation – first through influencing individual beliefs and values, and second through the communication and application of the NbS concept in research, policy, and practice. We argue that for NbS to support transformation, it must support a reframing of human-nature relationships, one where the interdependencies between people and nature are recognized as essential for social and environmental well-being. We elaborate on how such a framing is key to support inclusivity and collaboration between diverse research perspectives, policy objectives across scales, and implementation practices, to deliver successful NbS.

Abstract: The trend of fasting until noon (omission or delayed breakfast) is increasingly prevalent in modern society. This eating pattern triggers discordance between endogenous circadian clock rhythms and the feeding/fasting cycle and is associated with an increased incidence of obesity and T2D. Although the underlying mechanism of this association is not well understood, growing evidence suggests that fasting until noon, also known as an “extended postabsorptive state,” has the potential to cause a deleterious effect on clock gene expression and disrupted regulation of body weight, postprandial and overall glycemia, skeletal muscle protein synthesis, appetite and may also lead to lower energy expenditure. This manuscript overviews the clock gene-controlled glucose metabolism during the active and resting phases. The consequences of postponing until noon the transition from postabsorptive to fed state on glucose metabolism, weight control, and energy expenditure. Finally, we will discuss the metabolic advantage of shifting more energy, carbohydrates (CH), and proteins to the early hours of the day.

The novel coronavirus (COVID-19) was first reported in the U.S. on December 29, 2019 and has spread rapidly throughout the country, affecting individuals with varying severity due to their risk status. According to the Centers for Disease Control and Prevention, it is estimated that 45.4% of US adults are at higher risk for complications from coronavirus disease because of cardiovascular disease, diabetes, respiratory disease, hypertension, or cancer. In this study, we developed a mathematical model to assess the impact of a COVID-19 vaccine among low and high risk groups. Numerical simulations shows vaccinating both low and high risk groups simultaneously, rather than prioritizing the vaccine on high risk group only, further reduces the daily mortality. The result supports the need for an aggressive vaccination program, regardless of whether individuals are within the low or high risk population.

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.

The proposal of novel drugs and approaches for effective treatment of the novel coronavirus is a necessity after the quick outbreak of the disease. Since the commencement of the coronavirus spread, enormous efforts have been made to protect, alleviate and cure the disease, though no specific treatment has been approved. While there have been convincing results in the use of chemical drugs and interferon therapy, such therapeutic approaches have various drawbacks and lack the required performance for the treatment of the new coronavirus. Medicinal plant species can provide a solution as a source of natural antiviral compounds by the accumulation of secondary metabolites and lectins as well as acting as a platform to express the viral immunogenic proteins. This study reviews the advantages and the results of previous research for the treatment of the novel coronavirus disease and previous generations of similar coronaviruses. Several plant-derived anti coronavirus compounds have been nominated that could be targeted for further research due to the similarity of the coronavirus disease in 2003 and the current coronavirus. This review regards plant species such as Scutellaria baicalensis (Baikal skullcap), and Utrica dioica (Stinging nettle) as suitable candidates for the new coronavirus antiviral research. Furthermore, the use of plants such as Nicotiana tabacum (Tobacco) for the expression of the coronavirus viral antigens can be a target for the future vaccinal research of the new coronavirus due to the efficiency of expression and intrinsic antiviral properties.

The outbreak of recently identified 2019 novel coronavirus (2019-nCOV) infection has become a world-wide health threat. Currently, more information is needed for further understanding the transmission, clinical characteristics, and infection control procedures of 2019-nCOV. Recently, the role of the eye in transmitting 2019-nCOV has been intensively discussed. Previous investigations about other high infectious human COVs, that is, severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), may provide helpful information. In this review, we describe the genomics and morphology of human CoVs, the epidemiology, systemic and ophthalmic manifestations, mechanisms of human CoVs infection, and infection control procedures. The role of the eye in the transmission of SARS-CoV and 2019-nCOV is discussed. Although the conjunctiva is directly exposed to extraocular pathogens, and the mucosa of ocular surface and upper respiratory tract is connected by nasolacrimal duct and share same entry receptors for some respiratory viruses. The eye is rarely involved in human CoVs infection, conjunctivitis is quite rare in patients with SARS-CoV and 2019-nCoV infection, and COV RNA positive rate by RT-PCR test in tears and conjunctival secretions from patients with SARS-CoV and 2019-nCoV infection is also very low, which imply that the eye is neither a preferred organ of human COVs infection, nor is a preferred gateway of entry for human COVs to infect respiratory tract. However, pathogens exposed to the ocular surface might be transported to nasal and nasopharyngeal mucosa by constant tear rinsing through lacrimal duct, and then cause respiratory tract infection. Considering close doctor-patient contact is quite common in ophthalmic practice which are apt to transmit human COVs by droplets and fomites, hand hygiene and personal protection are still highly recommended for health care workers to avoid hospital-related viral transmission during ophthalmic practice.

Total-body PET/CT scanners provide increased sensitivity, enabling the adjustment of imaging parameters by reducing injected activity or shortening acquisition time. This study aimed to evaluate the limitations of reduced [18F]FDG activity doses on image quality, lesion detectabil-ity, and quantification of lesion uptake in the Biograph Vision Quadra, as well as to assess the benefits of the recently introduced ultra-high sensitivity mode in a clinical setting. A number of 26 patients who underwent [18F]FDG-PET/CT (3.0 MBq/kg, 5 min. scan time) were included in this analysis. PET raw data was rebinned for shorter frame durations to simulate 5 min. scans with lower activities in high sensitivity (HS) and ultra-high sensitivity (UHS) modes. Image quality, noise, and lesion detectability (n=82) were assessed using a 5-point Likert scale. The co-efficient of variation (CoV), signal-to-noise ratio (SNR), tumor-to-background ratio (TBR), and standardized uptake values (SUV) including SUVmean, SUVmax, and SUVpeak were evaluated. Sub-jective image ratings were generally superior in UHS compared to HS mode. At 0.5 MBq/kg, le-sion detectability decreased to 95% (HS) and 98% (UHS). SNR was comparable at 1.0 MBq/kg in HS (5.7±0.6) and 0.5 MBq/kg in UHS (5.5±0.5). With lower doses, there were negligible reductions in SUVmean and SUVpeak, whereas SUVmax increased steadily. Reducing [18F]FDG activity to 1.0 MBq/kg (HS/UHS) in a total-body PET/CT provides diagnostic image quality without statistical-ly significant changes in uptake parameters. UHS mode improves image quality, noise, and le-sion detectability compared to HS mode.

Background: Chronic neurologic diseases are common sequelae of COVID. They severely impact the quality of life and increase the burden on healthcare systems. The long COVID neurological symptoms are due to the robust replication of SARS-CoV-2 in the nasal neuroepithelial cells, leading to neuroinvasion and inflammation of the central nerve system (CNS). Currently used medications and vaccines do not inhibit the robust SARS-CoV-2 replication in the nasal epithelial cells. EGCG-palmitate (EC16), a multifunctional compound, has the potential to become a novel intranasal-delivered drug for minimizing post-COVID neurologic symptoms. Method: EC16-containing formulations were developed and tested in vitro against human β coronavirus OC43 (CoV-OC43) using a TCID50 assay following three test protocols differing in exposure sequence. Results: EC16 formulations in normal saline, phosphate buffered saline, and cell culture medium were found to effectively inhibit human β-coronavirus infection (>99.99%) after a 30-min contact. A single 10-min application to cells after infection (i.e., without direct contact with the virus) resulted in >99% inhibition of viral replication. Conclusion: With its antiviral, antioxidant, anti-inflammatory, and neuroprotective properties, EC16 in nasal formulations could be further developed for clinical applications to COVID-19 patients for minimizing long COVID neurological symptoms.

During 2019, the number of patients suffering from cough, fever and reduction of WBC’s count increased. At the beginning, this mysterious illness was called “fever with unknown origin”. At the present time, the cause of this pneumonia is known as the 2019 novel coronavirus (2019-nCoV) or the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). The SARS-CoV-2 is one member of great family of coronaviruses. Coronaviruses can cause different kind of illnesses including respiratory, enteric, hepatic, and neurological diseases in animals like cat and bat. Coronaviruses are enveloped positive-stranded RNA viruses. The SARS-CoV-2 has some particular structures for binding to host cells, reproducing itself in cells and damaging human cells. The SARS-CoV-2 can bind angiotensin-converting enzyme 2 (ACE‐2) receptors and cause various difficulties for human. The SARS-CoV-2 can cause either not-serious issues like fever and cough or serious concerns such as multi-organ failure. Source(s) of SARS-CoV-2 is under debate. Malayan pangolin and bat are the most suspicious candidate for being sources of the SARS-CoV-2. The SARS-CoV-2 can be transmitted by various ways such as transmitting from infected human to healthy human and can make severe pneumonia, which can lead to death. The SARS-CoV-2 can infect different kind of people with different ages, races, and social and economic levels. The SARS‐CoV‐2 infection can cause various sorts of clinical manifestations like cough and fever and intensity of signs and symptoms depends on sufferer conditions. Clinicians use all of available documents and tests like laboratory, histopathological and radiological findings for diagnosing new cases and curing patients with high accuracy. At the present time, there is no particular way for treating SARS-CoV-2 infection; neither antiviral drugs nor palliative agents. It seems that the best way for standing against the SARS-CoV-2 infection is preventing from it by social distancing and vaccination. This review tries to prepare an essential brief update about SARS-CoV-2 infection for clinicians.

The global spread of coronavirus disease (COVID -19) worldwide has had a significant effect on social and economic growth. The contamination keeps on advancing quickly and eccentrically, representing a significant test to its recognition and conclusion. Coronaviruses are commonly recognized by seclusion from tests, regardless of whether natural or clinical, utilizing some atomic science procedures, which can take a few days. In this work an analytical review of virus transmission, methods of diagnosing COVID -19 using artificial intelligence techniques to classify images and types of biosensors. At long last, the deformities and points of interest of each kind of sensor are recognized and examined. This exploration gives an explanatory audit of the utilization of crown infection COVID-19 in 2019. Related examinations were led utilizing five dependable databases, for example, Science Direct, IEEE Xplore, Scopus, Web of Science, and PubMed. An acceptable investigation is remembered for this audit, which can be depended upon as a logical database to put resources into another technique for recognizing COIVD-19.

This paper aims to quantify the effect of the deadly novel coronavirus (COVID-19) pandemic outbreak on Chinese stock market performance. Shanghai Stock Exchange Composite Index and its component sector indices are examined in this study. The pandemic is represented by a lockdown dummy, new COVID-19 cases and a dummy for 3 February 2020. First, descriptive analysis is performed on these indices to compare their performances before and during the lockdown period. Next, regression analysis with Exponential Generalized Autoregressive Conditional Heteroscedasticity specification is estimated to quantify the pandemic effect on the Chinese stock market. This paper finds that health care, information technology and telecommunication services sectors were relatively more pandemic-resistant, while other sectors were more severely hurt by the pandemic outbreak. The extent to which each sector was affected by pandemic and sentiments in other financial and commodity markets were reported in details in this paper. The findings of this paper are resourceful for investors to avoid huge loss amid pandemic outburst and the China Securities Regulatory Commission in handling future pandemic occurrence to cool down excessive market sentiments.

The outbreak across the globe due to coronavirus disease 2019 (COVID-19) has spread abruptly by infected humans worldwide. The continuous efforts by scientists is on way to understand how pandemic of COVID-19 resembles and differs from serve acute respiratory syndrome coronavirus (SARS-CoV) at transcriptomic and genomic level. The SARS-CoV and COVID-19 exploits the angiotensin converting enzyme 2 (ACE2) receptor to gain entry inside the cells.We analyzed the entry COVID-19 into host cell due to receptor binding domain (RBD) of spike glycoprotein. The proposed simulation data shows similar ternary structures from two viruses shares approximately 80 percent identity in amino acid sequences. Our molecular modeling investigation signifies that angiotensin converting enzyme 2 (ACE2) has stronger interaction with COVID -19 RBD. The Amino acid phenylaniline F486 LOOP plays vital role due to its penetration into hydrophobic pocket in ACE2.The said investigation of S-Glycoprotein RBD of COVID-19 or SARS-CoV-2 via ACE2 provides post genome analysis of protein-protein interaction for rapid assessing transmission of infected patients by deadly CoVID-19. The scientific data extracted implies early guidance to control and viral prevention of CoVID-19.

The disease of COVID-19 comprises the most serious against human health worldwide with a high rate of virulence and mortality. The disease is caused by the 2019-nCoV virus from the beta coronavirus family. The virus makes use of its surface glycoprotein named S protein or spike to enter the human cells. The virus attached to its receptor named angiotensin-converting enzyme 2 on host cells surface via its receptor-binding domain and its fusion is mediated by cleavage at S2' site that is carried out by surface protease. Vaccines or drugs interfering with S protein binding or cleavage sites could be considered as drugs to get rid of the infection. In the current work and though docking and molecular dynamic experiments we have checked more than 100 drugs with high enough molecular weights for their shielding potency toward S protein binding sites and processing S2' sites. Our results indicate the shielding potency of: fidaxomicin > ivermectin > heparin > azithromycin > clarithromycin > eryhthromycin > niclosamide > ritonavir. Considering affluent reports regarding the complex disturbance in the immune system and multi-organ involvement in the disease there is no single or binary drug regime for cure expectedly and instead, we claim the multi-drug regime should be the choice in this context. Accordingly, we suggest our extracted drugs as an adjuvant for clinical trials.

Recently, the outbreak of coronavirus disease 2019 (COVID-19) is threatening human health globally. There is a dire need to find potential therapeutic agents. Angiotensin converting enzyme 2 (ACE2), as an entry receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is considered as potential therapeutic target in COVID-19 pandemic. Here, our bioinformatics analysis revealed that the biological function of ACE2 was correlated with regulation of blood pressure and mediation of SARS-CoV-2 entry into host cells. Ten ACE2 cooperative proteins were identified by using STRING with a high score. ACE2 expressed highly in the small intestine, testis, and kidney. The level of ACE2 expression in tumor tissues varies in different types of cancers compared with that in normal tissues. It was worth noting that the expression level of ACE2 in the tumor has no effect on patient survival. MiRNA hsa-miR-942-5p, and three transcription factors (TFs) including Signal transducer and activator of transcription 4 (STAT4), Estrogen related receptor α (ESRRA), and Signal transducer and activator of transcription 3 (STAT3) were selected as novel ACE2 regulators. Moreover, nine potential therapeutic drugs were predicted by two online databases. Thus, our research may expand the overall view of ACE2 in COVID-19 treatment.

This review chronicles the indirect transmission method which seems to be overlooked by most people and makes attempts to clearly document the various transmission ways with a hope that such information may strengthen the knowledge base of researchers towards methods of eradicating the pandemic. Current knowledge of transmission and exposure of SARS-CoV-2 has been explained. Various researchers have put forward different ways of exposure and transmission. Literature does not reveal whether the indirect transmission route is the dominant one. However total lockdown could be a veritable means to reduce both direct and indirect transmission routes. In many countries where the indirect transmission has been reduced, the scourge of the virus is less. The work creates awareness on the need to watch out for those routes of transmissions that may not be popular and suggested key knowledge gaps that needs to filled.

The potential for transmission of the SARS-CoV-2 virus during minimally invasive gynaecological procedures, such as hysteroscopy or laparoscopy, on the reproductive tract of patients with COVID-19 is not known. We examined existing data for prevalence of virus in the reproductive tract and other bodily fluids.

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China and has subsequently spread worldwide. In the absence of any antiviral or immunomodulatory therapies, the disease is spreading at an alarming rate. 5 to 10% of recovered patients in Wuhan test positive again; this suggest that for controlling COVID-19, vaccines may be better option than drugs. A clinical trial to evaluate an anti-COVID-19 vaccine has started recently. However, its efficacy and potency have to be evaluated and validated. As an alternative, we are presenting a first-of-its-kind, designed multi-peptide subunit based epitope vaccine against COVID-19. The vaccine construct comprise an adjuvant, CTL, HTL, and B-cell epitopes joined by linkers. The vaccine is non-toxic, non-allergenic, thermostable and immunogenic with the capability to elicit a humoral and cell-mediated immune response. The findings are validated with high-end computation-based methods. This unique vaccine is made up of 33 highly antigenic epitopes from three proteins that have a prominent role in host receptor recognition, viral entry, and pathogenicity. We advocate this vaccine must be synthesized and tested urgently as public health priority.

The COVID-19 pandemic is placing unprecedented stress on healthcare systems around the world. Although Radiation Oncology Departments are not at the frontline of fighting this infectious disease, it is important to implement COVID-19 policies to reduce risk of staff and patient exposure, and to limit the risk of department shutdown or downtime. This brief report describes the policy implemented at George Washington University Radiation Oncology to manage the risks of COVID-19. This includes a General Statement related to the priorities of the Radiation Oncology department, a screening procedure for new and follow-up patients, management policies for critical and non-critical patients with COVID-19 or under quarantine, a policy for the management of patients currently under treatment who are diagnosed or placed in quarantine, a clinical escalation action plan, guidelines for staff meetings and travel, and procedure management. This policy was implemented at George Washington University Radiation Oncology after the first case of COVID-19 was reported in Washington DC on March 7, 2020.

Rosavin, a phenylpropanoid in Rhodiola rosea's rhizome, an adaptogen, is known for enhancing the body's response to environmental stress. It significantly affects cellular metabolism in health and many diseases, particularly influencing bone tissue metabolism. In vitro, rosavin inhibits osteoclastogenesis, disrupts F-actin rings formation, and lowers osteoclastogenesis-related gene expression (cathepsin K, CTR, TRAF6, TRAP, MMP-9). It also impedes NFATc1, c-Fos, NF-κB, and MAPK signaling pathways, and blocks phosphorylation processes crucial for bone resorption. Moreover, rosavin promotes osteogenesis, osteoblast differentiation and increases Runx2 and OCN expression. In vivo studies show its effectiveness in enhancing BMD in PMOP mice, re-straining osteoclast maturation, and increasing active osteoblast percentage in bone tissue. It modulates mRNA expressions (increasing EEF2 and decreasing HDAC1, thereby activating os-teoprotective epigenetic mechanisms) and alters various serum markers, including decrease of CTX-1, TRAcp5b, RANKL, M-CSF, TRAP, and increase of ALP and OCN. Additionally, when combined with zinc and probiotics, it reduces pro-osteoporotic MMP-3, IL-6, TNF-α, and en-hances anti-osteoporotic IL-10 and TIMP3 expressions. This paper aims to systematically review rosavin's impact on bone tissue metabolism, exploring its potential in osteoporosis prevention and treatment, and suggesting future research directions.

This review explores the transformative impact of sensor technologies in early disease detection. It highlights recent advancements in nanotechnology-based sensors, particularly focusing on their applications in identifying disease biomarkers at early stages. The integration of these sensors with artificial intelligence for predictive analytics in healthcare is also discussed. Applications in cancer, infectious diseases, and chronic disease management underscore their diverse utility. Challenges in sensor technology adoption and future directions, including multiplexed sensors and wearable devices, are examined. This review underscores sensors' potential in enhancing disease management and patient outcomes.

Herpesvirus is a prevalent pathogen that primarily infects human epithelial cells and has the ability to reside in neurons. In the field of otolaryngology, herpesvirus infection primarily leads to hearing loss and vestibular neuritis, and is considered the primary hypothesis regarding the pathogenesis of vestibular neuritis. In this review, we provide a summary of the effects of herpes virus on cellular processes in both host cells and immune cells, with a focus on HSV-1 as illus-trative examples.

Energy demand has exponentially increased with the increase in the world population and ur-banization. Renewable energy is clean, renewable, and environmentally friendly. Hydrogen production through Proton Exchange Membrane (PEM) electrolyzer is an efficient way to produce renewable energy. The efficiency and energy consumption of the PEM electrolyzer depends on the feed water quality. In this report, we study the effect of pH, TDS, and conductivity on hydrogen production as well as energy consumption during the process. pH values (3, 7, 9), TDS values (300ppm, 600ppm, 900ppm), and conductivity values (30mS/cm, 70mS/cm, 100mS/cm) were studied to understand and optimize the hydrogen production using PEM electrolyzer. The in-vestigations showed that hydrogen production is significantly affected by pH, total dissolved solids, and conductivity, and the best levels of each variable were identified by extensive testing. The findings show both the scientific significance of proton exchange electrolysis in meeting the growing energy demands of society as well as the importance of knowing the influence that di-verse conditions have on the creation of hydrogen. Our research, in general, contributes to the expanding body of scientific knowledge on the topic of the effective production of hydrogen and offers useful insights for the continuation of investigation in this field.

The article is aimed at a brief comparison and analysis of the results of queries to IEEE Xplore and the leading abstract databases Scopus and Web of Science to identify research trends. Some errors in the Author Keywords in Web of Science have been revealed. Therefore, a more detailed analysis was conducted by comparing different types of key terms for IEEE Xplore and Scopus platforms only. I used IEEE Access journal metadata as indexed on both platforms. The sample match for IEEE Xplore and Scopus was achieved by comparing DOI. The IEEE Xplore metadata contains more types of key terms, which provides an advantage in analyzing research trends. Using NSPEC Controlled Terms from expert-compiled vocabulary provides a more stable data, which gives an advantage when considering the change of terms over time. Apriori, an algorithm for finding association rules, has been used to compare co-occurrence of terms for a more detailed description of sample subjects on both platforms. VOSviewer was used to analyze trends in scientific research based on IEEE Xplore data. The 2011-2021 ten-year period was divided into two sub-intervals for comparing the occurrence of Author Keywords, IEEE Terms, and NSPEC Controlled Terms. Using the IEEE conference proceedings bibliometric data, I illustrated the importance of context in estimating the rate of growth of publishing activity on a topic of interest.

Intravitreal injection is the gold standard therapeutic option for posterior segment pathologies, and long-lasting release is necessary to avoid reinjections. There is no effective intravitreal treatment for glaucoma or other optic neuropathies in daily practice, nor is there a non-invasive method to monitor drug levels in the vitreous. Here we show that a glaucoma treatment combining a hypotensive and neuroprotective intravitreal formulation (IF) of brimonidine-Laponite (BRI/LAP) can be monitored non-invasively using vitreous imaging captured with optical coherence tomography (OCT) over 24 weeks of follow-up. Qualitative and quantitative characterization was achieved by analysing the changes in vitreous (VIT) signal intensity, expressed as a ratio of retinal pigment epithelium (RPE) intensity. Vitreous hyperreflective aggregates mixed in the vitreous and tended to settle on the retinal surface. Relative intensity and aggregate size progressively decreased over 24 weeks in treated rat eyes as the BRI/LAP IF degraded. VIT/RPE relative intensity and total aggregate area correlated with brimonidine levels measured in the eye. The OCT-derived VIT/RPE relative intensity may be a useful and objective marker for non-invasive monitoring of BRI/LAP IF.

Besides the increase in global energy demand, access to clean energy, reduction in greenhouse gas emissions caused by conventional power generation sources, energy security, and availability of electricity in remote villages in emerging nations are some of the factors that foster the use of renewable energy sources (RESs) in generating electricity. One of the aims of initiating microgrids (MGs) is to maximize the benefits of RES and alleviate the associated grid integration issues. Microgrids are made up of RES connected to electrical loads within clearly delineated electrical limits that operate as individual controllable units on the electrical network. It can operate in-dependently as well as in connection with the grid. The paper presents an overview of microgrids and investigates the system's performance when connected to and disconnected from the grid. Furthermore, in both modes of operation, the functioning and behavior of system components such as the bidirectional DC-DC converter and energy storage system (ESS) were evaluated. The architecture of the proposed microgrid consists of a small hydropower plant, a wind farm, and a battery energy storage system (BESS). The microgrid under investigation is modeled and simu-lated using MATLAB and Simulink.

We aimed to determine if infection-associated urine biomarkers can differentiate true urinary tract infection (UTI) from non-UTI controls. Midstream clean-catch urine samples were collected from asymptomatic volunteers and symptomatic subjects > 60 years old diagnosed with presumptive UTI in a specialty setting. Microbial identification and density were assessed using multiplex PCR/pooled antibiotic susceptibility test (M-PCR/P-AST) and standard urine culture (SUC). Three biomarkers (NGAL, IL-8, and IL-1β) were measured in the same urine specimens. Definitive UTI cases were symptomatic and had positive microorganism detection by SUC and M-PCR, while definitive non-UTI cases were asymptomatic volunteers regardless of microbial detection. We observed a strong positive correlation (R2 ≈ 1) between microbial density and the biomarkers NGAL, IL-8, and IL-1β. Biomarker consensus criteria of two or more positive biomarkers had sensitivity 90.2%, specificity 91.2%, positive predictive value (PPV) 91.7%, negative predictive value (NPV) 89.7%, accuracy 90.7%, positive likelihood ratio of 10.28, and negative likelihood ratio of 0.11 in differentiating definitive UTI from non-UTI cases, regardless of microbial density. NGAL, IL-8, and IL-1β showed a significant elevation in symptomatic cases with positive microbe identification compared to asymptomatic cases with or without microbe identification. Biomarker consensus exhibited high accuracy in distinguishing UTI from non-UTI cases.

When working with the novel coronavirus SARS-CoV-2 during a pandemic response, having a rapid, reproducible and reliable assay for infectious virus quantitation and utilization for evaluation of potential therapeutics is critical. Compared to traditional agarose overlay plaques visualized with neutral red, assays performed with Avicel R RC-591 semi-solid overlay provide a simplified format for rapid and easy detection and neutralization testing. The method is easily modified for higher throughput using dispensers or automated processing. Fixation using formalin provides flexibility when dealing with pathogenic agents such as SARS-CoV-2 where tissue culture plates might be removed from biocontainment for staining. Although plaque assays are considered straightforward in principle, having an easily reproducible, consistent plaque assay is an invaluable tool.

The outbreak of Coronavirus disease 2019 (COVID-19) has posed a significant concern in many countries due to the rapid rate of transmission between humans. Taking advantage of the experience of the last epidemics in 2002 Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and 2012 Middle East Respiratory Syndrome Coronavirus (MERS-CoV), some regions of the world were well- prepared for the new outbreak. However, other countries needed to be adapted to the situation promptly. Many management strategies were established, and some restrictions were introduced in some regions. In this review, we aimed to determine countries’ public responses to the epidemic of COVID-19 and how they developed administrative approaches towards the outbreak.

Coronavirus, also known as COVID-19, has been declared a pandemic by the World Health Organization (WHO). At the time of conducting this study, it had recorded over 1.6 million cases while more than 105,000 have died due to it, with these figures rising on a daily basis across the globe. The burden of this highly contagious respiratory disease is that it presents itself in both symptomatic and asymptomatic patterns in those already infected, thereby leading to an exponential rise in the number of contractions of the disease and fatalities. It is therefore crucial to expedite the process of early detection and diagnosis of the disease across the world. The case-based reasoning (CBR) model is an effective paradigm that allows for the utilization of cases’ specific knowledge previously experienced, concrete problem situations or specific patient cases for solving new cases. This study therefore aims to leverage the very rich database of cases of COVID-19 to solve new cases. The approach adopted in this study employs the use of an improved CBR model for state-of-the-art reasoning task in classification of suspected cases of Covid19. The CBR model leverages on a novel feature selection and semantic-based mathematical model proposed in this study for case similarity computation. An initial population of the archive was achieved with 68 cases obtained from the Italian Society of Medical and Interventional Radiology (SIRM) repository. Results obtained revealed that the proposed approach in this study successfully classified suspected cases into their categories at an accuracy of 97.10%. The study found that the proposed model can support physicians to easily diagnose suspected cases of Covid19 base on their medical records without subjecting the specimen to laboratory test. As a result, there will be a global minimization of contagion rate occasioned by slow testing and as well reduce false positive rates of diagnosed cases as observed in some parts of the globe.

Copper-containing materials are attracting attention as self-desinfecting surfaces, suitable for helping healthcare settings in reducing healthcare associated infections. However, the impact of repeated exposure to disinfectants frequently used in biocleaning protocols on their antibacterial activity remains insufficiently characterized. This study aimed at evaluating the antibacterial effi-ciency of copper (positive control), a brass alloy (AB+®) and stainless steel (negative control) after repeated exposure to a quaternary ammonium compound and/or a mix of peracetic acid/hydrogen peroxide routinely used in healthcare settings. A panel of 6 antibiotic-resistant strains (clinical isolates) was selected for this assessment. After a short (5 min) exposure time, the copper and brass materials retained significantly better antibacterial efficiencies than stainless steel, whatever the bacterial strain or disinfectant treatment considered. Moreover, post-treatment with both disinfectant products, copper-containing materials still reached similar levels of antibacterial efficiency as those obtained before treatment. Antibiotic resistance mechanisms such as efflux pump overexpression did not impair the antibacterial efficiency of copper-containing materials, neither did the presence of one or several genes related to copper homeostasis/resistance. In light of those results, surfaces made out of copper and brass remain interesting tools in the fight against dissemination of antibiotic-resistant strains that might cause healthcare associated infections.

The goal of newborn screening is to improve health outcomes by identifying and treating affected newborns. This manuscript provides an overview of a data tool to facilitate the longitudinal collection of health information on newborns diagnosed with a condition through NBS. The Newborn Screening Translational Research Network (NBSTRN) developed the Longitudinal Pediatric Data Resource (LPDR) to capture, store, analyze, visualize, and share genomic and phenotypic data over the lifespan of NBS identified newborns to facilitate understanding of genetic disease, and to assess the impact of early identification and treatment. NBSTRN developed a consensus-based process using clinical care experts to create, maintain, and evolve question and answer sets organized into common data elements (CDEs). The LPDR contains 24,172 core and disease-specific CDEs for 118 rare genetic diseases, and the CDEs are being made available through the NIH CDE Repository. The number of CDEs for each condition average of 2,200 with a range from 69 to 7,944. The LPDR is used by state NBS programs, clinical researchers, and community-based organizations. Case level, de-identified data sets are available for secondary research and data mining. The development of the LPDR for longitudinal data gathering, sharing, and analysis supports research and facilitates the translation of new discoveries into clinical practice.

Our investigations show that electrochemical corrosion of copper is faster than electrochemical corrosion of aluminium at temperatures below 100oC. Literature data analysis shows that the Al atoms diffuse faster than the Cu atoms at temperatures higher than 475oC, Al rich intermetallic compounds (IMCs) are formed faster in the Cu-Al system, and the Kirkendall plane shifts toward Al side. Electrochemical corrosion occurs due to electric current and due to diffusion. An electronic devise working time, for example, depends on initial copper cover thickness on aluminium wire, connected to the electronic devise, temperature, and volume and dislocation pipe diffusion coefficients, so copper, iron, and aluminium electrochemical corrosion rates are investigated experimentally at room temperature and at temperature 100oC. Intrinsic diffusivities ratios of copper and aluminium at different temperatures and diffusion activation energies in the Cu-Al system are calculated by proposed here methods using literature experimental data. Dislocation pipe and volume diffusion activation energies of pure iron are calculated separately by earlier proposed method using literature experimental data. Aluminium dissolved into NaCl solution as the Al3+ ions at room temperature and at temperature 100oC, iron dissolved into NaCl solution as the Fe2+ (not Fe3+) ions at room temperature and at temperature 100oC, copper dissolved into NaCl solution as the Cu+ ions at room temperature and as the Cu+ and the Cu2+ ions at temperature 100oC. It is founded experimentally that copper corrosion is higher than aluminium corrosion, and ratio of electrochemical corrosion rates, kCu/kAl>1, decreases with temperature increasing, although iron electrochemical corrosion rate doesn’t depend on temperature below 100oC. It is obvious, because melting point of iron is more higher then melting point of copper or aluminium. It is calculated that copper electrochemical corrosion rate is approximately equal to aluminium electrochemical corrosion at temperature about 300oC, so copper can dissolve into NaCl solution mostly as the Cu2+ ions at temperature about 300oC. Ratio of intrinsic diffusivities, DCu/DAl <1, increases with temperature increasing, and intrinsic diffusivity of aluminium could be approximately equal to intrinsic diffusivity of copper at temperature about 460oC.

COVID-19 is the first known coronavirus pandemic. Nevertheless, the seasonal circulation of the four milder coronaviruses of humans – OC43, NL63, 229E and HKU1 – raises the possibility that these viruses are the descendants of more ancient coronavirus pandemics. This proposal arises by analogy to the observed descent of seasonal influenza subtypes H2N2 (now extinct), H3N2 and H1H1 from the pandemic strains of 1957, 1968 and 2009, respectively. Recent historical revisionist speculation has focussed on the influenza pandemic of 1889-1892, based on molecular phylogenetic reconstructions that show the emergence of human coronavirus OC43 around that time, probably by zoonosis from cattle. If the “Russian influenza”, as The Times named it in early 1890, was not influenza but caused by a coronavirus, the origins of the other three milder human coronaviruses may also have left a residue of clinical evidence in the 19th century medical literature and popular press. In this paper, we search digitised 19th century British newspapers for evidence of previously unsuspected coronavirus pandemics. We conclude that there is little or no corpus linguistic signal in the UK national press for large-scale outbreaks of unidentified respiratory disease for the period 1785 to 1890.

The main manifestation of new coronavirus disease 2019 (COVID-19) is respiratory disease. The new coronavirus (SARS-CoV-2) attacks the lungs and may result in severe acute respiratory syndrome. In such cases, the infected person has difficulty breathing, which impairs oxygen uptake in the body. If pneumonia or another respiratory illness develops, and the host immune system is unable to combat SARS-CoV-2, the infected person may eventually die. Meanwhile, reports on unexpected symptoms in organs other than the nasal cavity, throat, and lungs are emerging. To elucidate the causes of such symptoms, we analyzed the expression status of angiotensin-converting enzyme 2 (ACE2), the host receptor used by SARS-CoV-2, in various tissues. This study confirmed that alveolar macrophages appear to be involved in pneumonitis and thrombus formation. In this report, we introduce some new symptoms.

A novel approach has been suggested to use isoelectric points of viral and human proteins to quickly identify proteins that are effective in not allowing virus particles to attach to human receptor cells by virtue of their electrical charge. The method has been applied to SARS CoV-2 to suggest potentially important human proteins that can be suitable for making anti-viral drugs.

A novel coronavirus, named 2019-nCoV, is responsible for current epidemic outbreaks in China and also other countries that cause acute pneumonia that was primarily linked to a seafood wholesale market in Wuhan, China. To control and prevent the existing epidemic outbreaks of coronavirus in China, a precise and easy disinfection/sterilization technique is important to disinfect/sterilize the mass-level peoples and their ambient environments (e.g. atmospheric air/aerosols). Among the disinfection techniques, control fire/flame (CF) could be applied. Large-size CF (LSCF) can be generated by using gas burner, gas cylinder that used in restaurant, coals, kerosene (petroleum), dried straws, dried woods) at entry and exit points of big gathering locations (e.g. hospital, airport, rail stations, seaports, apartments, streets/roads, etc. Additionally, small-size CF (SSCF) can be produced by using gas burner of kitchen, electric heater, kindle or waste papers at individual home and ward/room at hospital. Individual person can be soaked/immersed their hands and their belongings nearby CF for a moment, likely followed sterilization during quantification of the number of bacteria in experimental observation, that can rapidly sterilize the person perfectly. Correspondingly, the ambient air/aerosols moved towards CF due to water evaporation by fire that subsequently refresh all ambient air/aerosols by killing all viruses. Such CF could certainly reach the temperature higher than 56 degree C that could effectively disinfect/sterilize/kill the coronavirus. Therefore, CF could be effectively applied to control and prevent the epidemic outbreaks of coronavirus across China and worldwide.

This study aims to investigate the effects of chest mobilization and breathing exercises on respiratory function, trunk stability, and endurance in chronic stroke patients who have contracted coronavirus disease (COVID-19). Thirty inpatients of a tertiary hospital in South Korea, who had a history of COVID-19 and were diagnosed with stroke within the last 6 months were randomly assigned to either the Chest Mobilization Exercise with Breathing Exercise (CMEBE) or Conservative Physical Therapy with Breathing Exercise (CPTBE) groups. The respiratory function, trunk stability, and endurance were measured at baseline and 6 weeks after the interventions. Both CMEBE and CPTBE groups showed improvements in respiratory function, trunk stability, and endurance after the intervention (p<0.05). However, the CMEBE group showed significantly greater improvements in forced expiratory volume in 1 second (p<0.05), trunk stability (p<0.05), and endurance (p<0.05) than the CPTBE group. No significant intergroup difference was observed in forced vital capacity and peak expiratory flow. Conclusion: The combination of chest mobilization and breathing exercises improved respiratory muscle mobility and endurance, stabilized the trunk, and enhanced balance and transfer of weight. The findings suggest that this intervention could be beneficial in improving respiratory function and endurance in stroke patients.

Coronavirus disease 2019 restrictions impacted Canadians' daily living, especially those at higher risk of compromised health conditions. This study aimed to describe the physical, psychological, and social well-being of adults with disabilities, and older adults from May to June 2020. An online survey was used to administer standardized measures of mobility, anxiety and depression, boredom, resilience, technology readiness, social support, social networks, and participation. Seventy-two participants were recruited, with a mean age (SD) of 61.2 (13.8). 69.4% of participants had a disability, and 51.4% were older adults. 27.8% and 16.7% of participants exceeded the anxiety and depression cut-off scores, respectively. Boredom and restriction in participation were experienced by 76.4% and 80.1% of participants, respectively. Participants' mean (SD) resilience and life space scores were 72.4 (14.0) and 51.9 (24.0), respectively. Individuals with disabilities have comparatively higher mean anxiety (5.5 to 3.3), depression (4.8 to 2.9), and boredom (92.2 to 72.3) scores than those without. Individuals with a disability had lower resilience (69.9 to 78.0) and felt more life space restrictions (45.4 to 67.6). Our findings revealed issues with anxiety, boredom, participation, and life space activity. This information may provide supporting evidence when creating policies to mitigate existent health and social inequities.

Coronaviruses are an extensive family of viruses that can cause disease in both animals and humans. The current classification of coronaviruses recognizes 39 species in 27 subgenera that belong to the family Coronaviridae. From those, at least seven coronaviruses are known to cause respiratory infections in humans. Four of these viruses can cause common cold-like symptoms, while others that infect animals can evolve and become infectious to humans. Three recent examples of this viral jumps include SARS CoV, MERS-CoV and SARS CoV-2 virus. They are responsible for causing severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and the most recently discovered coronavirus disease during 2019 (COVID-19).COVID-19, a respiratory disease caused by the SARS-CoV-2 virus, was declared a pandemic by the World Health Organization (WHO) on 11 March 2020. The rapid spread of the disease has taken the scientific and medical community by surprise. Latest figures from 14 April 2020 show more than 2 million people had been infected with the virus, causing more than 120,000 deaths in over 210 countries worldwide. The large amount of information we receive every day concerning this new disease is so abundant and dynamic that medical staff, health authorities, academics and the media are not able to keep up with this new pandemic. In order to offer a clear insight of the extensive literature available, we have conducted a comprehensive literature review of the SARS CoV-2 Virus and the Coronavirus Diseases 2019 (COVID-19).

The 2019-nCoV has been identified as the cause of an outbreak of respiratory illness in Wuhan, Hubei Province, China beginning in December 2019. This epidemic had spread to 19 countries with 11,791 confirmed cases, including 213 deaths, as of January 31, 2020. The World Health Organization declared it as a Public Health Emergency of International Concern. This study analyzed and discussed 70 research articles published until January 31, 2020 for a better understanding of the epidemiology, causes, clinical diagnosis, prevention and control of this virus. Studies thus far have shown origination in connection to a seafood market in Wuhan, but specific animal association has not been confirmed. The reported symptoms include fever, cough, fatigue, pneumonia, headache, diarrhea, hemoptysis, and dyspnea. Preventive measures such as masks, hand hygiene practices, avoidance of public contact, case detection, contact tracing, and quarantines are effective for reducing the transmission. To date, no specific antiviral treatment is proven effective, hence, infected people primarily rely on symptomatic treatment and supportive care. Although these studies had relevance to control a public emergency, more research need to be conducted to provide valid and reliable ways to manage this kind of public health emergency in both short- and long- term.

KLHL genes and the related KBTBD genes encode components of the Cullin-E3 ubiquitin ligase complex and typically target tissue-specific proteins for degradation, thereby affecting differentiation, homeostasis, metabolism, cell signaling, and the oxidative stress response. Despite their importance in normal cell function and in disease (KLHL40, KLHL41, KBTBD13, KEAP1, and ENC1), previous studies that examined epigenetic factors affecting transcription were predominantly limited to promoter DNA methylation. Using diverse tissue and cell culture whole-genome profiles, we examined 17 KLHL or KBTBD genes preferentially expressed in skeletal muscle or brain to identify tissue-specific enhancer and promoter chromatin, open chromatin (DNaseI hypersensitivity), and DNA hypomethylation. Sixteen of the 17 genes displayed muscle- or brain-specific enhancer chromatin in their gene bodies, and most exhibited specific intergenic enhancer chromatin as well. Seven genes were embedded in a super-enhancer. The enhancer chromatin regions typically displayed foci of DNA hypomethylation at peaks of open chromatin. In addition, we found evidence that gene neighbors (HHATL and FBXO32) of KLHL40 and KLHL38 harbor enhancer chromatin that likely upregulates the adjacent KLHL gene. Many KLHL/KBTBD genes had tissue-specific promoter chromatin at their 5’ ends, but surprisingly, two (KBTBD11 and KLHL31) had constitutively unmethylated promoter chromatin in their 3’ exons that overlaps a retrotransposed KLHL gene. Our findings demonstrate the importance of expanding epigenetic analyses beyond the 5’ ends of genes in studies of normal and abnormal gene regulation.

Novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) are constantly threatening global public health. With no end date, the pandemic still persists with the emergence of novel variants that threaten the effectiveness of diagnostic tests and vaccines. Mutations in the Spike surface protein of the virus are regularly observed in the new variants, potentializing the emergence of novel viruses with different tropism from the current ones, which may change the severity and symptoms of the disease. Growing evidence has shown that mutations are being selected in favor of variants that are more capable of evading the action of neutralizing antibodies. In this context, the most important factor guiding the evolution of SARS-CoV-2 is its interaction with the host’s immune system. Thus, as current vaccines cannot block the transmission of the virus, measures complementary to vaccination, such as the use of masks, hand hygiene, and keeping environments ventilated remain essential to delay the emergence of new variants. Importantly, in addition to the involvement of the immune system in the evolution of the virus, we highlight several chemical parameters that influence the molecular interactions between viruses and host cells during invasion and are also critical tools making novel variants more transmissible. In this review, we dissect the impacts of the Spike mutations on biological parameters such as (1) increase of Spike binding affinity to hACE2; (2) bound time for the receptor to be cleaved by the proteases; (3) how mutations associate with increase of RBD up-conformation state in the Spike ectodomain; (4) expansion of uncleaved Spike protein in the virion particles; (5) increment of Spike concentration per virion particles; and (6) evasion of the immune system. These factors play key roles in the fast spreading of SARS-CoV-2 variants of concern, including the Omicron.

The very first infected novel coronavirus case (COVID-19) was found in Hubei, China in Dec. 2019. The COVID-19 pandemic has spread over 215 countries and areas in the world, and has significantly affected every aspect of our daily lives. At the time of writing this article, the numbers of infected cases and deaths still increase significantly and have no sign of a well-controlled situation, e.g., as of 14 April 2020, a cumulative total of 1,853,265 (118,854) infected (dead) COVID-19 cases were reported in the world. Motivated by recent advances and applications of artificial intelligence (AI) and big data in various areas, this paper aims at emphasizing their importance in responding to the COVID-19 outbreak and preventing the severe effects of the COVID-19 pandemic. We firstly present an overview of AI and big data, then identify their applications in fighting against COVID-19, next highlight challenges and issues associated with state-of-the-art solutions, and finally come up with recommendations for the communications to effectively control the COVID-19 situation. It is expected that this paper provides researchers and communities with new insights into the ways AI and big data improve the COVID-19 situation, and drives further studies in stopping the COVID-19 outbreak.

Background and objectives: Unrestricted kinematic alignment total knee arthroplasty (KA-TKA) with a soft tissue respecting technique (STRT) is a soft tissue-dependent tibial resection entailing restoration of the original soft tissue tension using ligamentotaxis after resurfacing the femur, based on the concept of restoring the native or pre-osteoarthritis alignment in each patient. However, there is no consensus on the indications of unrestricted KA-TKA with STRT. We modified the STRT, followed by investigation of the effects of surgery on the postoperative hip-knee-ankle angle (HKAA). Materials and Methods: We retrospectively analyzed the clinical background data, including the preoperative and postoperative HKAA, of 87 patients who underwent unrestricted KA-TKA with the modified STRT. Univariate and multivariate analyses were performed to determine the factors affecting the postoperative HKAA. A receiver operating characteristic (ROC) curve was plot-ted to investigate the change in the cut-off values of preoperative HKAA with respect to the safe zone of the postoperative HKAA. We generated two regression models, the linear regression model and generalized additive model (GAM) using machine learning, to predict the postopera-tive HKAA. Results: Univariate and multivariate analyses revealed the preoperative HKAA as the factor most relevant to the postoperative HKAA. ROC analysis revealed that the preoperative HKAA exhibited high predictive utility, with a cut-off value of -10°, when the safe range of postoperative HKAA was set at ± 5°. The GAM was the superior machine learning model, indicating a non-linear association between the preoperative and postoperative HKAA. Patients with preoperative HKAAs ranging from -18° to 4° were more likely to fall within the ± 5° safe range of the postoperative HKAA. Conclusions: The preoperative HKAA influences the postoperative HKAA in unrestricted KA-TKA with the modified STRT. Machine learning using the GAM may contribute to the selection of patients eligible for the surgical approach.

One of the important research directions in the field of photovoltaics is integration with construction. The integration of solar cell systems with a building can reduce installation costs and help optimize the used space. One of the interesting types of cells is dye-sensitized solar cells. In addition to their interesting properties, they also have aesthetic value. In the classic arrangement, they are constructed using glass with a transparent conductive layer (TCL). This article describes replacing a classic glass counter electrode with an electrode based on a ceramic tile and nickel foil. This solution makes it possible to expand their construction applications. The advantage of this solution is full integration with construction while simultaneously generating electricity. A dye-sensitized solar cell was built layer-by-layer on ceramic tile and nickel foil. An atomization method was used to deposit fluorine-doped tin oxide, and then a screen printing method was used to deposit a platinum layer. The electrical parameters of the manufactured DSSCs with and without a counter electrode tile were characterized by measuring their current-voltage characteristics under standard AM 1.5 radiation. A dye-sensitized solar cell integrated with ceramic tiles and nickel foil was produced and displayed an efficiency of over 4%.

Abstract: The promise of regenerative medicine and tissue engineering is founded on the ability to regenerate diseased or damaged tissues and organs into functional tissues and organs or the creation of new tissues and organs altogether. In theory, all damaged and diseased tissues and organs can be regenerated or created using different configurations and combinations of extracellular matrix, cells and inductive biomolecules. Currently, regenerative medicine and tissue engineering can allow the improvement of patients’ quality of life through availing novel treatment options. Tissues and organs have a specific ECM, with specific proteins and factors released by cells residing within the local microenvironment. The coupling of regenerative medicine and tissue engineering field with 3D printing is revolutionizing the treatment of patients in a huge way. 3D bioprinting allows the proper placement of cells and ECMs, allowing the recapitulation of native microenvironments of tissues and organs. 3D bioprinting utilizes different bioinks made up of different formulations of ECM/biomaterials, biomolecules and even cells. The choice of the bioink used during 3D bioprinting is very important as properties such as printability, compatibility and physical strength influence the final construct printed. The extracellular matrix (ECM) provides both physical and mechanical microenvironment needed by cells to survive and proliferate. Decellularized ECM bioink contains biochemical cues from the original native ECM and also the right proportions of ECM proteins. Different techniques and characterization methods are used to derive bioinks from several tissues and organs and to evaluate their quality. This review discusses the uses of decellularized ECM bioinks and argues that they represent the most biomimetic bioinks available. In addition, we briefly discuss some polymer-based bioinks utilized in 3D bioprinting.

Plants produce specific structures constituting a barrier hindering penetration of pathogens, while they also produce substances inhibiting pathogen growth . These compounds are secondary metabolites, such as phenolics, terpenoids, sesquiterpenoids, resins, tannins and alkaloids. Bioactive compounds are secendary metabolities from trees and shrubs are used in medicine, herbal medicine and cosmetology. To date fruits and flowers of exotic trees and shrubs have been primarily used as sources of bioactive compounds. In turn, search for new sources of bioactive compounds is currently focused on native plant species due to its availability. Application of such raw material needs to be based on knowledge of their chemical composition, particularly health-promoting or therapeutic compounds. Research conducted to date on European trees and shrubs has been scarce. This paper presents results of literature studies conducted to systematise knowledge on bioactive compounds found in trees and shrubs native to central Europe. The aim of this review providing available information on the subject is to indicate gaps in the present knowledge.

Gal-3BP is a multifunctional glycoprotein involved in cell-cell and cell-matrix interactions known to be upregulated in cancer and various viral infections, including HIV-1, HCV and SARS-CoV-2, with a key role in regulating the antiviral immune response. Studies have identified a direct correlation between circulating levels of Gal-3BP and the severity of disease and/or disease progression for some viral infections, including SARS-CoV-2, suggesting a role of Gal-3BP in these processes. Due to Gal-3BP’s complex biology, the molecular mechanisms underlying its role in viral diseases have been only partially clarified. Gal-3BP induces the expression of IFN and pro-inflammatory cytokines, including interleukin-6, mainly interacting with galectin-3, targeting TRAF-6 and TRAF-3 complex, thus having a putative role in the modulation of TGF-β signaling. In addition, an antiviral activity of Gal-3BP has been ascribed to a direct interaction of the protein with virus components. In this review, we explored the role of Gal-3BP in viral infections and the relationship between Gal-3BP upregulation and disease severity and progression, mainly focusing on SARS-CoV-2. Augmented knowledge of Gal-3BP role in virus infections can be useful to evaluate its possible use as a prognostic biomarker and as a putative target to block or attenuate severe disease.

We report the first detection of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus from a dog in Connecticut during February 2021. Complete genome sequencing and phylo-genetic analysis of the hCoV-19/USA/CT-CVMDL-Dog-1/2021 (CT_Dog/2021) virus were con-ducted to identify the origin and lineage of the virus. The CT_Dog/2021 virus belonged to the GH/B1.2. genetic lineage and was genetically close to SARS-CoV-2 identified from humans in the U.S. during the winter of 2020-2021. However, it was not related to other SARS-CoV-2 identified from companion animals in the U.S. It contained both D614G in spike and P323L in nsp12 substitutions which have become the dominant mutations in the United States. The continued sporadic detections of SARS-CoV-2 in companion animals warrant public health concerns about their potential to become a new reservoir species of SARS-CoV-2.

The COVID-19 pandemic is one of the worst catastrophes that we have faced globally in recent years. It has not only taken its toll on the economic sector but also on the education sector. The social distancing norms that are in place as a direct response to the pandemic have turned conventional classroom teaching into a problematic minefield; as such, students all over the world have been forced into unprecedented situations that have served only to worsen the situation. The current pandemic has given rise to one of the worst crises the 21^st Century has ever seen, resulting in a surge of unemployment. Many companies have taken the route of firing employees or making redundancies, as they cannot afford the monthly reimbursement for staff. While this issue primarily concerns full-time workers, it also carries significant consequences for students – a considerable number of students are required to earn their daily living costs, and, without a job, they cannot pay their educational fees, accommodation costs, or living expenses. This comprehensive study briefly discusses the multitude of problems faced by students in the UK regarding higher education, as a direct result of the coronavirus pandemic. It contains six individual sections: a detailed introduction; the methodological procedures employed; educational disruptions, covering issues from hindrances in field research to examinations and student evaluations; personal problems experienced by students, such as accommodation and loss of income; concerns arising from the global pandemic; and finally, a conclusion and summary of the study’s findings.

Coronavirus disease 2019 (COVID-19) is caused by infection with the 2019 novel coronavirus 2 (2019-nCoV, now referred to as SARS-CoV-2). COVID-19 has become a global pandemic since its outbreak at the end of Dec 2019. COVID-19 could lead to severe acute respiratory disease, especially to those who have reduced immunity. Binding of the viral Spike protein (S) to its receptor ACE2 (Angiotensin Converting Enzyme 2) on the surface of target cells has been proven to be key for virus entry and infection. Although ACE2 expression in the respiratory system is necessary for pneumonia infection by SARS-CoV-2, the regulation of ACE2 gene expression remains poorly investigated, especially for patients that are in pre-pathological conditions. Here, by analyzing The Gene Expression Omnibus (GEO) database, we investigated the expression regulation of ACE2 in various kinds of primary epithelial cells from the respiratory system after varies of respiratory viruses infection such as influenza A virus (IFV), respiratory syncytial virus (RSV) and human rhinovirus (hRV). Our analyses reveal that infection of multiple kinds of respiratory viruses or influenza vaccines greatly increased ACE2 expression, suggesting that respiratory viruses infection could represent a high risk factor for developing COVID-19. We also found that the regulatory effect of influenza A virus on ACE2 expression is associated with activation of the interferon beta-induced pathway and viral RNA-activated host response. Together, our data provide a theoretical framework for clinical classification for SARS-CoV-2 infection susceptibility and could be used for future prevention and therapy treatment for COVID-19.

It is not established whether SARS-CoV-2 (COVID-19) patients with movement disorders, are at greater risk for more serious outcomes than the larger COVID-19 population beyond the susceptibility associated with greater age. We reviewed electronic health records and conducted telephone interviews to collect the demographics and clinical outcomes of patients seen at our Movement Disorders Center who tested positive for COVID-19 from 8 March 2020 through 6 June 2020. Thirty-six patients were identified, 23 men and 13 women, median age of 74.5 years. They primarily carried diagnoses of idiopathic Parkinson disease (n=22; 61%) and atypical parkinsonism (n=7; 19%) with the balance having other diagnoses. Twenty-seven patients (75%) exhibited alteration in mental status and fifteen (42%) had abnormalities of movement as common manifestations of COVID-19; in 61% and 31%, these were the presenting symptoms of the disease. 67% of patients in our cohort required hospitalization, and the mortality rate was 39%.. These data demonstrate that in patients with movement disorders, the likelihood of hospitalization and death after contracting COVID-19 was substantially greater than in the general population. Patients with movement disorders frequently presented with altered mental status, generalized weakness, or worsening mobility but not anosmia.

The world is facing new challenges every day; however, with the spread of the pandemic around the world, this new challenge is different. The pandemic is increasing and concentrating various challenges simultaneously. Although different sectors are facing consequences, the most important sectors, that is, health and economy are the most affected. When the pandemic began, it was not known how long it would last, which complicated health and economic planning. Therefore, it is important for decision makers and the public to know the predictions and expectations of the future of these challenges. In this work, the current situation is analyzed. Then, an expectation model is developed based on the statistics of the pandemic using a growth rate model based on an exponential and logarithmic rate of increase. Based on the available open data about the pandemic spread, the model can successfully predict future expectations, including the duration and maximum number of cases of the pandemic. The model uses the equilibrium point as the day the cases decrease. The model can be used for planning and the development of strategies to overcome these challenges.

There is a lot of discussion underway with conflicting opinions examining the airborne nature of the SARS-CoV2 virus. Surprisingly, important phenomena prevalent with respect to aerosols (suspended droplets) have not been considered. In this Technical Note, we propose a methodology for the coupling of aerosol phenomena (such as evaporation, particle transport accounting for drag) to accurately establish the lifetimes of the droplets. A characteristic time analysis illustrates the time scales for evaporation and settling: for example, the characteristic time for evaporation of a 10 µm droplet is 0.036 s at a relative humidity of 25%; compared to a settling time of about 500 s. For any particle smaller than ~ 100 µm, the evaporation of the emitted or exhaled droplet has to be considered. Coupling evaporation of the droplet as it settles, we estimate the horizontal distance traversed. Trajectories of a 10 µm and 100 µm particle emitted with a typical initial velocity of release associated with coughing and sneezing indicates the greater spread in the horizontal direction when evaporation is accounted for. The life time of the 10 µm particle increases from 8.3 min to 12 hours (will be intercepted prior and the actual airborne time will then be shorter); and for a 100 µm particle from 4.9 s to 39.4 s.

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2/2019-nCoV) infection is an emerging pandemic. The virus binds to angiotensin converting enzyme 2 (ACE2) and TMPRSS2 which are abundantly expressed on various human cells including lung epithelial cells and intestinal cells and the virus can infect these cells. Currently no specific treatments or vaccines are available for this disease. A per oral live attenuated vaccine can be beneficial in SARS-Cov-2 infection because the attenuated virus initially infects the gut, stimulates the mucosa associated immune system sparing the respiratory system during the initial immune response. The live virus can also spread in the community boosting herd immunity.

Data on pathologic changes of the 2019 novel coronavirus disease (COVID-19) are scarce. To gain knowledge about the pathology that may contribute to disease progression and fatality, we performed post-mortem needle core biopsies of lung, liver, and heart in four patients who died of COVID-19 pneumonia. The patients’ ages ranged from 59 to 81, including 3 males and 1 female. Each patient had at least one underlying disease, including immunocompromised status (chronic lymphocytic leukemia and renal transplantation) or other conditions (cirrhosis, hypertension, and diabetes). Time from disease onset to death ranged from 15 to 52 days. All patients had elevated white blood cell counts, with significant rise toward the end, and all had lymphocytopenia except for the patient with leukemia. Histologically, the main findings are in the lungs, including injury to the alveolar epithelial cells, hyaline membrane formation, and hyperplasia of type II pneumocytes, all components of diffuse alveolar damage. Consolidation by fibroblastic proliferation with extracellular matrix and fibrin forming clusters in airspaces is evident. In one patient, the consolidation consists of abundant intra-alveolar neutrophilic infiltration, consistent with superimposed bacterial bronchopneumonia. The liver exhibits mild lobular infiltration by small lymphocytes, and centrilobular sinusoidal dilation. Patchy necrosis is also seen. The heart shows only focal mild fibrosis and mild myocardial hypertrophy, changes likely related to the underlying conditions. In conclusion, the post-mortem examinations show advanced diffuse alveolar damage, as well as superimposed bacterial pneumonia in some patients. Changes in the liver and heart are likely secondary or related to the underlying diseases.

An outbreak of novel coronavirus(2019-nCoV) that began in Wuhan, China, is rapidly spreading to all over China, and gradually to multiple countries. Regarding to put the epidemic prevention and spread under the control, early identification and diagnosis play a critical role. Patients with initially no or mild symptoms of Novel Coronavirus Pneumonia (2019-nCoV), namely “stealth” infection, often lack of typical clinical evidence to establish the diagnosis. Based on the clinical analysis of 4 cases in stealth infection, the results of this study highlight that early diagnosis requires a combination of epidemiological history, clinical manifestations, early chest CT examination, and 2019-nCoV RNA test (nucleic acid test), with particular emphasis on definite epidemiological history and early chest CT findings when positive nucleic acid tests lag behind.

Abstract: The aim of this study is to emphasize on the clinical uses of amniotic membrane (AM) in multiple ocular disorders. AM possesses many properties including promotion of epithelialization, anti-fibrotic, anti-apoptotic, anti-angiogenic properties. Epithelial wound healing on the eye surface is promoted due to several epidermal and keratocyte growth factors as well as by its anti-inflammatory and anti-scarring effects due to interleukin-10, interleukin-1 receptor antagonists and inhibition of transforming growth factor- beta (TGF-β) signal transduction by AM in the corneal and conjunctival fibroblasts respectively. It plays a crucial role by functioning as a substitute of basement membrane (BM) and as a temporary graft material. It is not only being used as an eye graft but also its extract can be used as an eye drop for corneal and external eye diseases. So its proper preparation, preservation and clinical application can bring a revolutionary change in the treatment of different ocular disorders.

SARS-CoV-2 infection produces a response of the innate immune system causing oxidative stress and a strong inflammatory reaction termed ‘cytokine storm’ that is one of the leading causes of death. Paraoxonase-1 (PON1) protects against oxidative stress by hydrolyzing lipoperoxides. Alterations in PON1 activity have been associated with pro-inflammatory mediators such as the chemokine (C-C motif) ligand 2 (CCL2) and the glycoprotein galectin-3. We aimed to investigate the alterations in the circulating levels of PON1, CCL2 and galectin-3 in 126 patients with COVID-19 and their interactions with clinical variables and analytical parameters. A machine learning approach was used to identify predictive markers of the disease. For comparisons, we recruited 45 COVID-19 negative patients and 50 healthy individuals. Our approach identified a synergy between oxidative stress, inflammation and fibrogenesis in positive patients that is not observed in negative patients. PON1 activity was the parameter with the greatest power to discriminate between patients who were either positive or negative for COVID-19, while their levels of CCL2 and galectin-3 were similar. We suggest that the measurement of serum PON1 activity may be a useful marker for the diagnosis of COVID-19.

The pandemic history of pathogenic SARS-CoV-2 associated COVID-19 infection began in December 2019, with its emergence in Wuhan, China. Pertaining to its high transmissibility and wide host adaptability, this new and unique human coronavirus spread across the planet affecting almost every country, inflicting 91 million people and causing 1.9 million deaths (as of January 17th, 2021). Limited or negligible pre-existing immunity to multiple SARS-CoV-2 variants has resulted in severe morbidity and mortality worldwide, as well as a record-breaking surge in the use of medical-surgical supplies and personal protective equipments. In response to the global need for effective sterilization techniques, this study evaluated the virucidal efficacy of FATHHOME’s self-contained, ozone-based dry-sanitizing device, by dose and time response assessment. We tested inactivation of human coronavirus, HCoV-OC43, a close genetic model of SARS-CoV-2, on porous (N95 filtering facepiece respirator/FFR) and nonporous (glass) surfaces. We started our assays with 20 ppm of ozone for 10 min exposure, which was able to effectively reduce, 99.8% and 99.9% of virus from glass and N95 FFR surfaces, respectively. Importantly, the virus was completely inactivated, below the detection limit (over 6-log10 reduction) with 25 ppm ozone for 15 mins on both tested surfaces. As expected, a higher ozone concentration (50 ppm) resulted in faster inactivation of HCoV-OC43 with 100% inactivation in 10 mins from both the surfaces, with no residual ozone present after completion of the 5-minute post exposure recapture cycle and no measurable increase in ambient ozone levels. These results confirmed that FATHHOME’s device may provide a safe and viable solution for rapid decontamination of SARS-CoV-2- from worn items, frequently touched items, and PPE including N95 FFRs, face shields and other personal items.

To understand SARS-CoV-2 microevolution, this study explored the genome-wide frequency, gene-wise distribution, and molecular nature of all point-mutations detected across its 71,703 RNA-genomes deposited in the GISAID repository, till 21 August 2020. Globally, nsp1/nsp2/nsp3/ nsp11 and orf7a/orf3a/S were the most mutation-ridden non-structural and structural genes respectively. Phylogeny based on 4,618 spatiotemporally-representative genomes revealed that entities belonging to the early lineages are mostly spread over Asian countries (including India, the biggest hotspot of the pandemic) whereas the recently-derived lineages are more globally distributed. Of the total 16,602 polymorphism-bearing sites in the pan-genome, 11,037 and 4,965 involved transitions and transversions, which in turn were predominated by cytidine-to-uridine and guanosine-to-uridine conversions, respectively. Positive selection of nonsynonymous mutations (dN/dS >1) in most of the structural, but not non-structural, genes indicated that SARS-CoV-2 has already harmonized its replication/transcription machineries with the host’s metabolic system, while it is still redefining virulence/transmissibility strategies at the molecular level.

During its first month, the recently emerged 2019 Wuhan novel coronavirus (SARS-CoV-2) has already infected many thousands of people in mainland China and worldwide and took hundreds of lives. However, the swiftly spreading virus also caused an unprecedentedly rapid response from the research community facing the unknown health challenge of potentially enormous proportions. Unfortunately, the experimental research to understand the molecular mechanisms behind the viral infection and to design a vaccine or antivirals is costly and takes months to develop. To expedite the advancement of our knowledge we leverage the data about the related coronaviruses that is readily available in public databases, and integrate these data into a single computational pipeline. As a result, we provide a comprehensive structural genomics and interactomics road-maps of SARS-CoV-2 and use these information to infer the possible functional differences and similarities with the related SARS coronavirus. All data are made publicly available to the research community at http://korkinlab.org/wuhan .

Abstract Antibacterial activities can be improved using mixed ligands. Mixed ligands involved in this research are sodium sulfadiazine (Na-sfz) and dithiocarbamate (ai-dtc). One-pot synthesis was used to synthesize ligand of aniline dithiocarbamate (ai-dtc) and the corresponding coordination compounds of [VO(sfz)(ai-dtc)] and [Zn(sfz)(ai-dtc)]. Crystals of ai-dtc, which grew from the solution when refrigerated after five days, were diffracted with technique of single crystal x-ray crystallography to reveal the structure. Other characterization techniques involving physicochemical parameters, FT-IR, UV-Vis and NMR (1H NMR and 13C NMR) were carried out on ligands of ai-dtc, sfz and corresponding coordination compounds. Differences in results of FT-IR, UV-Vis and NMR between ligands and their respective metal ions confirmed the coordination. The in vitro antibacterial studies showed that the ligands (not the metal complexes) had modest activity against Gram negative bacteria: Staphylococcus aureus, whereas, the coordination compounds had modest activities against the Gram negative bacteria: Escherichia coli and Pseudomonas aeruginosa.

ABSTRACT: Recurrent glioblastoma (rGBM) is a highly aggressive form of brain cancer that poses a significant challenge for treatment in neurooncology, and the survival status of patients after relapse usually means rapid deterioration, and also the leading cause of death among patients. In recent years, immunotherapy has emerged as a promising strategy for the treatment of recurrent glioblastoma by stimulate the body's immune system to recognize and attack cancer cells , which could be used as a in combination with other treatments such as surgery, radiation, and chemotherapy to improve outcomes for patients with recurrent glioblastoma, This therapy combines several key methods such as the use of monoclonal antibodies, chimeric antigen receptor T cell (CAR-T) therapy, checkpoint inhibitors, oncolytic viral therapy cancer vaccines, and combination strategies. In this review, we mainly document the latest immunotherapies for the treatment of glioblastoma and focus on the rGBM especially.

The present short communication aimed to determine the effects of vegetable cultivation on health. We conducted a qualitative study using responses to an open-ended question that was part of a survey on regional differences on vegetable intake. Participants in this study were residents of Gunma Prefecture, Japan, and were aged between 20–74 years. In the questionnaire, we asked: “Aside from increasing vegetable intake, how does vegetable cultivation affect your health?” We were able to categorize the answers into six subcategories related to physical health, mental health, and social well-being.

A B S T R A C T Genital herpes disease is caused mainly by herpes simplex virus type 2 (HSV-2), which is sexually transmitted with a high prevalence in both developed and developing countries. No vaccine is currently available against genital herpes. In this study, we introduced and expressed two genes encoding HSV-2 glycoprotein D (gD) and VP16 protein and a GFP marker gene (control) in tobacco seedlings. Positive plant infection was assessed through characteristic tobacco mosaic virus disease symptoms on leaves and by monitoring the fluorescence emitted by the expressed GFP protein. Expression of the HSV-gD2 and VP16 antigens was verified by RT-PCR, ELISA and Western blot. As a proof of concept, the immunogenicity and the protection ability of the plant produced gD antigen was tested in a mouse model of genital herpes and compared to gD antigen produced in a mammalian expression system. This showed that the plant-gD preparation, when used in combination with a CpG oligodeoxynucleotide as adjuvant, was highly immunogenic and capable of inducing complete immunity to lethal vaginal HSV-2 challenge in mice. Thus, the data presented here may have implications for the development of a production system for highly immunogenic plant-based HSV-2 vaccine antigens.

Vitamin D plays an important role in maintaining healthy mineralized skeleton. It is also consid-ered an immunomodulatory agent that regulate the innate and adaptive immune systems. Multi-ple observational studies have demonstrated the association between low level of serum 25-hydroxyvitamin D [25(OH)D] and presence and severity of several rheumatic diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), spondyloarthropathies and oste-oarthritis (OA). Nevertheless, the specific benefits of vitamin D supplement for treatment and prevention of rheumatic diseases are less accepted as the results from randomized clinical trials are inconsistent, although some conceivable benefits of vitamin D for improvement of disease ac-tivity of RA, SLE and OA have been demonstrated in meta-analyses. It is also possible that some individuals might benefit from vitamin D differently from others since inter-individual difference in responsiveness to vitamin D supplementation has been observed in genomic studies. Although the optimal level of serum 25(OH)D is still debatable, it is advisable it is advisable that patients with rheumatic diseases should maintain serum 25(OH)D level at least 30 ng/mL (75 nmol/L) to prevent osteomalacia, secondary osteoporosis and fracture, and possibly 40 – 60 ng/mL (100 – 150 nmol/L) to achieve maximal benefit from vitamin D for immune health and overall health.

As variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge, assessment of vaccine immunogenicity remains a critical factor to support continued vaccination. To this end, an in vitro microneutralization (MN50) assay was validated to quantitate SARS-CoV-2 neutralizing antibodies against ancestral and variant strains (Beta, Delta, Omicron BA.1, Omicron BA.5 and XBB.1.5) in human serum. For ancestral strain, the MN50 assay met acceptance criteria for inter-/intra-assay precision, specificity, linearity, and selectivity. The assay was robust against changes to virus/serum incubation time, cell seeding density, virus content per well, cell passage number, and serum interference. Analyte in serum samples was stable up to 5 freeze/thaw cycles and for up to 12 months of storage at –80 ± 10 °C. Similar results were observed for the variant-adapted MN50 assays. The conversion factor to convert assay result units to WHO international standard units (IU/mL) was determined to be 0.62 for the ancestral prototype strain. This MN50 assay will be useful for vaccine immunogenicity analyses in clinical trial samples, enabling assessment of vaccine immunogenicity for ancestral and variant strains as variant-adapted vaccines are developed.

The worldwide spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has ubiquitously impacted many aspects of life. As vaccines continue to be manufactured and administered, limiting the spread of SARS-CoV-2 will rely more heavily on the early identification of contagious individuals occupying reopened and increasingly populated indoor environments. In this study, we investigated the utility of an impaction-based aerosol sampling system with multiple nucleic acid collection media. Heat-inactivated SARS-CoV-2 was utilized to perform bench-scale, short-range aerosol, and room-scale aerosol experiments. Through bench-scale experiments, AerosolSense Capture Media (ACM) and nylon flocked swabs were identified as the highest utility media. In room-scale aerosol experiments, consistent detection of aerosol SARS-CoV-2 was achieved at a concentration equal to or greater than 0.089 genome copies per liter of room air (gc/L) when air was sampled for eight hours or more at less than one air change per hour (ACH). Shorter sampling periods (~75 minutes) yielded consistent detection at ~31.8 gc/L of room air and intermittent detection down to ~0.318 gc/L at (1 and 6+ ACH respectively). These results support further exploration in real-world testing scenarios and suggest the utility of indoor aerosol surveillance as an effective risk mitigation strategy in occupied buildings.

Recent emergence of novel coronavirus (SARS-CoV-2) all over the world has resulted more than 33,106 global deaths. To date well-established therapeutics modules for infected patients are unknown. In this present initiative, molecular interactions between FDA-approved antiviral drugs against the Hepatitis-C virus (HCV) have been investigated theoretically against the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2. HCV and SARS-CoV-2 are both +ssRNA viruses. At 25^o C beclabuvir, a non-nucleoside inhibitor of the RdRp_HCV can efficiently bind to RdRp _SARS-CoV-2 (ΔG_AutoDock = -9.95 kcal mol^-1) with an inhibition constant of 51.03 nM. Both the ΔG_London and ΔG_{GBVI / WSA} values were - 9.06 and - 6.67 kcal mol^-1, respectively for binding of beclabuvir to RdRp_SARS-CoV-2. In addition, beclabuvir has also shown better binding free energy with RdRp_SARS-CoV-2 (ΔG_vina = -8.0 kcal mol^-1) than that observed with the Thumb 1 domain of RdRp_HCV (ΔG_vina = -7.1 kcal mol^-1). InterProScan has suggested the RNA-directed 5'-3' polymerase activity exists within 549^th to 776^th amino acid residues of RdRp_SARS-CoV, where the major amino acid residues interacting being I591, Y621, C624, D625, A690, N693, L760, D762, D763, and E813-N817. Molecular interaction suggests occupancy of beclabuvir inside the active site environment of the RdRp_SARS-CoV-2, the enzyme essential for viral RNA synthesis. In conclusion, results suggest beclabuvir may serve as an anti-SARS-CoV-2 drug.

Currently, there is no specific treatment for COVID-19 proven by clinical trials. WHO and CDC guidelines therefore endorse supportive care only. However, frontline clinicians have been applying several virus-based and host-based therapeutics in order to combat SARS-CoV-2. Medications from COVID-19 case reports, observational studies and the COVID-19 Treatment Guideline issued by the China's National Health Commission (7^th edition published March 3^rd, 2020. Edited translation attached) are evaluated in this review. Key evidence from relevant in vitro researches, animal models and clinical studies in SARS-CoV-2, SARS-CoV and MERS-CoV are examined. Antiviral therapies remdesivir, lopinavir/ritonavir and umifenovir, if considered, could be initiated before the peak of viral replication for optimal outcomes. Ribavirin may be beneficial as an add-on therapy and is ineffective as a monotherapy. Corticosteroids use should be limited without indicating comorbidities. IVIG is not recommended due to lack of data in COVID-19. Xuebijing may benefit patients with complications of bacterial pneumonia or sepsis. The efficacy of interferon is unclear due to conflicting outcomes in SARS and MERS studies. Chloroquine and hydroxychloroquine have shown in vitro inhibition of SARS-CoV-2 and may be beneficial as both prophylactic and treatment therapy. For patients who developed cytokine release syndrome, interleukin-6 inhibitors may be beneficial. Given the rapid disease spread and increasing mortality, active treatment with readily available medications may be considered timely prior to disease progression.

After the appearance of first cases of ‘pneumonia of unknown origin’ in the Wuhan city, China, during late 2019, the disease progressed fast. Its cause was identified as a novel coronavirus, named provisionally 2019-nCoV. Subsequently, an official name was given as SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) by the International Committee on Taxonomy of Viruses (ICTV) study group. The World Health Organization (WHO) named the Coronavirus disease-2019 as COVID-19. The epidemics of COVID-2019 have been recorded over 113 countries/territories/areas apart from China and filched more than 4292 humans, affecting severely around 1,18,326 cases in a short span. The status of COVID-2019 emergency revised by the WHO within 42 days from Public Health International Emergency (January 30, 2020) to a pandemic (March 11, 2020). Nonetheless, the case fatality rate (CFR) of the current epidemic is on the rise (between 2-4%), relatively is lower than the previous SARS-CoV (2002/2003) and MERS-CoV (2012) outbreaks. Even though investigations are on its way, the researchers across the globe have assumptions of animal-origin of current SARS-CoV-2. A recent case report provides evidence of mild COVID-2019 infection in a pet dog that acquired COVID-2019 infection from his owner in Hong Kong. The news on travellers associated spread across the globe have also put many countries on alert with the cancellation of tourist visa to all affected countries and postponement of events where international visits were required. A few diagnostic approaches, including quantitative and differential real-time polymerase chain reaction assays, have been recommended for the screening of the individuals at risk. In the absence of any selective vaccine against SARS-CoV-2, re-purposed drugs are advocated in many studies. This article discourse the current worldwide situation of COVID-2019 with information on virus, epidemiology, host, the role of animals, effective diagnosis, therapeutics, preventive and control approaches making people aware on the disease outcomes.

In May of 2022, millions of U.S. parents faced uncertainty in safely feeding their infants due to the infant formula shortage. Methods: An anonymous, electronic, cross-sectional, retrospective survey was used. Results: U.S. parents (n =187) whose infants were 10.2 weeks old during the short-age completed the survey. Eighty-one percent of parents switched formulas during the shortage, 87% switched because they could not find the formula they typically used, 34% switched 3-5 times, 29% of parents visited ≥ 4 stores/24 hours and 26% of parents traveled >20 miles/24 hours to purchase formula. Use of infant formula increased (p< 0.01); in infants requiring specialty for-mula, use of intact cow’s milk formula increased (p < 0.05) and use of premature infant formulas decreased (p < 0.05). Infants relying on specialty formulas experienced at least one undesirable outcome compared with non-specialty users. Parents used social media, relatives/friends, and healthcare providers for support during the shortage, but their helpfulness scores were suboptimal. Parents reported needs for greater infant formula availability, free prenatal lactation education and postpartum lactation support. Conclusions: Government, regulatory and healthcare policy oversight are needed to protect the infant feeding system, including more commercially available products, access to banked donor milk and lactation support.

Global differences in changes in the numbers of population-adjusted daily test-positive cases (NPDP) and deaths (NPDD) by COVID-19 were analyzed for 49 countries, including developed and developing countries. The changes as a proportion of national population were compared, adjusting by the beginning of test-positive cases increase (BPI) or deaths increase (BDI). Remarkable regional differences of more than 100 fold in NPDP and NPDD were observed. The trajectories of NPDD after BDI increased exponentially within 20 days in most countries. Machine learning analysis suggested that NPDD on 30 days after BDI was the highest in developed Western countries (1180 persons per hundred million), followed by countries in the Middle East (128), Latin America (97), and Asia (7). Furthermore, in Western countries with positive rates of the PCR test of less than 7.0%, the increase in NPDP was slowing-down two weeks after BPI, and subsequent NPDD was only 15% compared with those with higher positive rates, which suggested that the situation of testing might have affected the velocity of COVID-19 spread. The causes behind remarkable differences between regions possibly include genetic factors of inhabitants because distributions of the race and of the observed infection increasing rates were in good agreement globally.

Introduction: COVID-19 is an unprecedented global public health emergency currently impacting India in an unprecedented manner. Aim of this study was to assess knowledge, awareness, perceptions and related factors of Indian dentists on COVID-19. Methodology: A cross-sectional, on-line questionnaire-based study was conducted over one week between 3rd May, 2020 to 10th May, 2020. The sample comprised 403 Indian dentists in solo, group practices and in the academic arena. The self-administered questionnaire assessed 1) knowledge/awareness on factors related to COVID-19 patient identification and symptomatology, 2) knowledge/awareness of COVID-19 transmission and 3) perceptions of COVID-19 history taking procedure. Statistical analyses were conducted using Statistical Package for Social Sciences for Windows, version 21.0 (IBM Corp., Armonk, NY., USA). Frequency distributions and logistic regression analyses were used. Results: Indian dentists demonstrated an overall modest level of knowledge on identification of patients with COVID-19. Moreover, they had a high level of awareness of the COVID-19 transmission means, and the generally accepted procedural perceptions on patient history taking. However, there were some gaps in specific aspects of knowledge and perceptions. Those who were aged ≥ 30-years had a significantly higher level of knowledge of patient identification means than those who were < 30-years (OR=1.78:1.12-2.83); p=0.01. Moreover, specialized dentists were significantly knowledgeable of COVID-19 transmission means than the general dentists (OR=1.89:1.22-2.93; p=0.004). Conclusions: Our findings demonstrate identifiable gaps in knowledge/awareness and perceptions of COVID-19 in Indian dental professionals. These gaps should be fulfilled, at the earliest, due to the rising burden of COVID-19 in India, to ensure safe dental care delivery.

SARS-CoV-2 is a novel and highly pathogenic coronavirus, which was first diagnosed in Wuhan city, China, in 2019, and spread to 185 countries and territories, and as of April 29, 2020, more than 3.11 million cases were recorded, and more than 217,000 people were killed. Despite all worldwide efforts, there is currently no vaccine, any drugs available to protect people against deadly SARS-CoV-2 coronavirus. The world urgently needs a SARS-CoV-2 coronavirus vaccine or effective antiviral drugs to relieve the human suffering associated with the pandemic that kills thousands of people every day. The SARS-CoV-2 genome encode a non-structural proteins named as ORF1a/b, and structural proteins such as spike (S) glycoprotein, nucleocapsid protein (N), small envelop protein (E) and matrix protein (M). A number of studies have been shown that CoV spike (S) glycoprotein and nucleocapsid protein (N) could be promising targets for vaccine, antibodies and therapeutic drug development to combat with deadly, pandemic SARS-CoV-2. Purposes of the present paper is the sequence analysis and amino acid variations of structural proteins deduced from novel coronavirus SARS-CoV-2 strains, isolated in different countries. Multiple sequence alignment of S, N and E proteins from four different coronavirus species, are also described. It is expected that the data from these studies will be very useful for the the designing and development of vaccines, antibodies and therapeutic agents that can be used to combat with the highly pathogenic SARS-CoV-2 coronavirus worldwide.

Abstract: Sustainable use of Native American heritage places is viewed in this analysis as serving to preserve their traditional purposes and sustain the cultural landscapes that give them heritage meaning. The research is about the potential impacts of heritage tourism to selected Native American places at Arches National Park, Canyonlands National Park, and Hovenweep National Monument. The impacts of tourists to a heritage place must be understood as having both potential effects on the place itself and on an integrated cultural landscape. Impacts to one place potentially change other places- functions in a Native American landscape and the integrity of the landscape itself. The analysis is based on 696 interviews with representatives from nine tribes and pueblos, who in addition to defining the cultural meaning of places, officially made 349 heritage management recommendations. The U.S. National Park Service interprets Natives American resources and then brings millions of tourists to these through museums, brochures, outdoor displays, and ranger-guided tours. Native American ethnographic study participants argued that tourist education and regulation can increase the sustainability of Native American places in a park and can help protect related places beyond the park.

Abstract: Letter migrations between words in reading aloud (e.g., reading "cane love" as "lane love" or "lane cove") are known to result from a deficit in the visual-orthographic analysis and characterize attentional dyslexia. In spontaneous speech, individuals with impairment in the phonological output buffer may show migrations of phonemes between words. The purpose of this study was to examine whether migrations between words in reading aloud can also result from a deficit in the phonological output buffer, to explore the characteristics of migrations resulting from orthographic input and from phonological output deficits, and to examine methods to distinguish these two sources. Using tasks of reading aloud of 92-182 word pairs, we identified 18 adults and adolescents with developmental dyslexia who made between-word letter migrations in reading aloud, significantly more than age-matched controls (372 adults and 26 7th-graders). To distinguish between orthographic-input and phonological-output sources for these migrations, we administered a test assessing orthographic-input without spoken-output (written-semantic-decision on 140 migratable word pairs) and a test of repetition of 36 auditorily-presented migratable word pairs, assessing spoken output without orthographic-input (and word span tests). These tests indicated that the migrations of ten of the participants with dyslexia resulted from an orthographic-input deficit, and for the other eight participants, migrations resulted from a phonological-output deficit. We identified several differences between the two types of between-word errors: first, whereas the individuals with attentional dyslexia made omissions of a letter that appeared in the same position in the two words, the phonological output buffer group did not make such omissions. In addition, the groups differed in the origin of migration: orthographic input migrations involve letters that are orthographically adjacent, whereas phonological output migrations involve phonemes that have just been spoken or that are prepared together in the phonological buffer for production. This was manifested in that migrations from the line below and from two lines above occurred only in the orthographic input deficit group, and migrations occurred from a word vertically close to the target in the orthographic input group but from a word that has just been spoken (placed diagonally to the target) in the phonological output group. This study thus indicates that between-word migrations in reading-aloud can result not only from attentional dyslexia, but also from a phonological output buffer deficit, and offers ways to distinguish between the two.

Ocean big data is the scientific practice of using big data technology in the marine field. Data from satellites, manned spacecraft, space stations, airship, unmanned aerial vehicles, shore-based radar and observation stations, exploration platforms, buoys, underwater gliders, submersibles, and submarine observation networks are seamlessly combined into the ocean’s big data. Increasing numbers of scholars have tried to fully analyze the ocean’s big data. To explore the key research technology knowledge graphs related to ocean big data, articles between 1990 and 2020 were collected from the “Web of Science”. By comparing bibliometric software and using the visualization software Cite-Space, the pivotal literature related to ocean big data, as well as countries, institutions, categories, and keywords, were visualized and recognized. Journal co-citation analysis networks can help determine the national distribution of core journals. Co-citation analysis networks for documents show authors who are influential at key technical levels. Key co-occurrence analysis network keywords can determine research hot spots and research frontiers. The three supporting elements of marine big data research are shown in the co-citation network. These elements are author, institution, and country. By examining the co-occurrence of keywords, the key technology research directions for future marine big data were determined.

Background: Tumor microenvironment (TME) plays a crucial role in virtually every aspect of tumorigenesis of glioblastoma multiforme (GBM). The dysfunctional TME promotes drug resistance, disease recurrence and distant metastasis. Recent evidence indicates that exosomes released by stromal cells within TME may promote oncogenic phenotypes via transferring signaling molecules such as cytokines, proteins and microRNAs. Results: In this study, clinical GBM samples were collected and analyzed. We found that GBM-associated macrophages (GAMs) secreted exosomes which were enriched with oncomiR-21. Co-culture of GAMs (and GAM derived exosomes) and GBM cell lines resulted in the increased GBM cells’ resistance against temozolomide (TMZ) by upregulating pro-survival gene, PDCD4 and stemness markers Sox2, STAT3, Nestin and miR-21-5p and increased M2 cytokines, IL-6 and TGF-β1 secreted by GBM cells, promoting the M2 polarization of GAMs. Subsequently, pacritinib treatment suppressed GBM tumorigenesis and stemness; more importantly, pacritinib-treated GBM cells showed markedly reduced ability to secret M2 cytokines and reduced miR-21 enriched exosomes secreted by GAMs. Pacritinib-mediated effects were accompanied by a reduction of oncomiR miR-21-5p, by which tumor suppressor PDCD4 was targeted. We subsequently established a patient-derived xenograft models where mice bore patient GBM and GAMs. The treatment of pacritinib, and the combination of pacritinib/TMZ appeared to significantly reduce tumorigenesis of GBM/GAM PDX mice, overcome TMZ-resistance, and M2 polarization of GAMs. Conclusion: In summation, we showed that potential of pacritinib alone or in combination with TMZ for suppressing GBM tumorigenesis via modulating STAT3/miR-21/PDCD4 signaling. Further investigations are warranted for adopting pacritinib for the treatment of TMZ-resistant GBM in the clinical settings.

We use state-of-the-art computer-aided drug design (CADD) techniques to identify prospective inhibitors of the main protease enzyme, 3CLpro of the SARS-CoV-2 virus causing COVID-19. From our screening of over one million compounds including approved drugs, investigational drugs, natural products, and organic compounds, and a rescreening protocol incorporating enzyme dynamics via ensemble docking, we have been able to identify a range of prospective 3CLpro inhibitors. Importantly, some of the identified compounds had previously been reported to exhibit inhibitory activities against the 3CLpro enzyme of the closely related SARS-CoV virus. The top- ranking compounds are characterized by the presence of multiple bi- and monocyclic rings, many of them being heterocycles and aromatic, which are flexibly linked allowing the ligands to adapt to the geometry of the 3CLpro substrate site and involve a high amount of functional groups enabling hydrogen bond formation with surrounding amino acid residues, including the catalytic dyad residues H41 and C145. Among the top binding compounds we identified several tyrosine kinase inhibitors, which include a bioflavonoid, the group of natural products that binds best to 3CLpro. Another class of compounds that decently binds to the SARS-CoV-2 main protease are steroid hormones, which thus may be endogenous inhibitors and might provide an explanation for the age-dependent severity of COVID-19. Many of the compounds identified by our work show a considerably stronger binding than found for reference compounds with in vitro demonstrated 3CLpro inhibition and anticoronavirus activity. The compounds determined in this work thus represent a good starting point for the design of inhibitors of SARS-CoV-2 replication.

Since the outbreak of the novel coronavirus disease (COVID-19) at the end of 2019, the clinical presentation of the disease showed a great heterogeneity with a diverse impact between different subpopulations. Emerging evidence from different parts of the world showed significantly poor outcome among males compared to female patients. A better understanding of the molecular mechanisms behind this difference might be a fundamental step for a more effective and targeted response to the outbreak. For that reason, here we try to investigate the molecular basis of the gender variations in mortality rates related to COVID-19 infection. To achieve this, we used our in-house pipeline to process publicly available lung transcriptomic data from 141 females compared to 286 males. After excluding Y specific genes, our results showed a shortlist of 73 genes that are differentially expressed between the two groups. Our results showed downregulation of a group of genes that are involved in the regulation of hydrolase activity including (AGTR1, CHM, DDX3X, FGFR3, SFRP2, and NLRP2), which is also believed to be essential for lung immune response and antimicrobial activity in the lung tissues in males compared to females. In contrast, our results showed an upregulation of angiotensin II receptor type 1 (AGTR1), a member of the renin-angiotensin system (RAS) that plays a role in angiotensin-converting enzyme 2 (ACE2) activity modulation. Interestingly, recent reports and experimental animal models highlight an important role of this receptor in SARS-Coronavirus lung damage as well as pulmonary edema, suggesting a possible role of its blockers like losartan and olmesartan as potential therapeutic options for COVID-19 infection. Finally, our results also showed a differential expression of different genes that are involved in the immune response including the NLRP2 and PTGDR2, further supporting the notion of the sex-based immunological differences. Taken together, our results provide an initial evidence of the molecular mechanisms that might be involved in the differential outcomes observed between both genders during the COVID-19 outbreak. This might be essential for the discovery of new targets and more precise therapeutic options to treat COVID-19 patients from different clinical and epidemiological characteristics with the aim of improving their outcome.

Currently, with a large number of fatality rates, coronavirus disease-2019 (COVID-19) has emerged as a potential threat to human health worldwide. It has been well-known that severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is responsible for COVID-19 and World Health Organization (WHO) proclaimed the contagious disease as a global pandemic. Researchers from different parts of the world amalgamate together inquest of remedies for this deadly virus. Recently, it has been demonstrated that the spike glycoprotein (SGP) of SARS-CoV-2 is the mediator behind the entrance into the host cells. Our group has comprehensibly analyzed the SGP of SARS-CoV-2 through multiple sequence analysis along with the phylogenetic analysis. Further, this research work predicted the most immunogenic epitopes for both B-cell and T-cell. Notably, we focused mainly on major histocompatibility complex (MHC) class I potential peptides and predicted two epitopes; WTAGAAAYY and GAAAYYVGY, that bind with the MHC class I alleles which are further validated by molecular docking analysis. Furthermore, this study also proposed that the selected epitopes were shown availability in a greater range of the population. Hence, our study comes up with a strong base for the implementation of designing novel vaccine candidates against SARS-CoV-2, however adequate laboratory works will need to be conducted for the appropriate application.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel evolutionarily divergent RNA virus etiological agent of COVID-19, is responsible for present devastating pandemic respiratory illness. To explore the genomic signatures, we comprehensively analyzed 2,492 complete and/or near-complete genome sequences of SARS-CoV-2 strains reported from across the globe to the GISAID database up to 30 March 2020. Genome-wide annotations revealed 1,407 nucleotide-level mutations at different positions throughout the entire genome of SARS-CoV-2. Moreover, nucleotide deletion analysis found nine deletions throughout the genome, including in polyprotein (n=6), ORF10 (n=1) and 3´-UTR (n=2). Evidence from the systematic gene-level mutational and protein profile analyses revealed a large number of amino acid (aa) substitutions (n=722), making the viral proteins heterogeneous. Notably, residues of receptor-binding domain (RBD) having crucial interactions with angiotensin-converting enzyme 2 (ACE2), and cross-reacting neutralizing antibody were found to be conserved among the analyzed SARS-CoV-2 strains, except for replacement of Lysine with Arginine at 378 position of the cryptic epitope of a Shanghai isolate, hCoV-19/Shanghai/SH0007/2020 (EPI_ISL_416320). Our method of genome annotation is a promising tool for monitoring and tracking the epidemic, the associated genetic variants, and their implications for the development of effective control and prophylaxis strategy.

Background: Coronavirus disease 2019 (COVID-19) pandemic are causing significant damages to many nations. For mitigating its risk, Japan’s Prime Minister called on all elementary, junior high and high schools nationwide to close beginning March 1, 2020. However, its effectiveness in decreasing disease burden has not been investigated. Methods: We used daily data on the report of COVID-19 and coronavirus infection incidence in Japan until March 31, 2020. Time series analysis were conducted using Bayesian method. Local linear trend models with interventional effect were constructed for number of newly reported cases of COVID-19, including asymptomatic infections. We considered that the effects of intervention start to appear 9 days after the school closure; i.e., on March 9. Results: The intervention of school closure did not appear to decrease the incidence of coronavirus infection. If the effectiveness of school closure began on March 9, mean coefficient α for effectiveness of the measure was calculated to be 0.08 (95% credible interval -0.36 to 0.65), and the actual reported cases were more than predicted, yet with rather wide credible interval. Sensitivity analyses using different dates also showed similar results. Conclusions: School closure carried out in Japan did not show the effectiveness to mitigate the transmission of novel coronavirus infection.

The ongoing pandemic of the 2019 novel coronavirus disease (COVID-19) raises a global health crisis, which has resulted in 75,778 confirmed cases with 2130 deaths in China and beyond. Atypical symptom renders it challenging to earlier recognize the 2019-nCoV carrier with the potential ability of equivalent transmission. Therefore, it is needed to gain full spectrum of COVID-19. Here we report clustered COVID-19 cases of person-to-person transmission. The symptoms of typical pneumonia are shared by the two familial members, namely son (Patient 1) and father (Patient 2). Unexpectedly, an influenza-like illness (ILI) is also caused in Patient 3 having close contact with Patient 1 at personal dinner party. Combined with clinical and epidemiological study, chest computed tomography (CT) and molecular diagnosis demonstrate that all the three cases tested positive for COVID-19 with distinct symptoms by human-to-human transmission. To the best of knowledge, it closes in part (if not all), a missing gap of clinical repertoires of COVID-19 outbreaks and underlines the possibility that neglection of cryptic/asymptomatic/mild cold-like syndromes gives biased screen in the earlier stage of COVID-19 cases.

There is currently a lack of pathologic data on the novel coronavirus (SARS-CoV-2) pneumonia, or COVID-19, from autopsy or biopsy. Two patients who recently underwent lung lobectomies for adenocarcinoma were retrospectively found to have had COVID-19 at the time of surgery. These two cases thus provide important first opportunities to study the pathology of COVID-19. Pathologic examinations revealed that, apart from the tumors, the lungs of both patients exhibited edema, proteinaceous exudate, focal reactive hyperplasia of pneumocytes with patchy inflammatory cellular infiltration, and multinucleated giant cells. Hyaline membranes were not prominent. Since both patients did not exhibit symptoms of pneumonia at the time of surgery, these changes likely represent an early phase of the lung pathology of COVID-19 pneumonia.

In this report, we demonstrate that it is possible to design epitope-based peptide vaccine candidates to counteract the novel China coronavirus (2019-nCoV) by using an approach similar to the one used in cancer neoantigen vaccination therapy. We identified multiepitope peptide vaccine candidates against 2019-nCov that can potentially trigger both CD4⁺ and CD8⁺ T cell immune response with increased efficiency due to the presence of CD4⁺ and CD8⁺ T cell epitopes and a cathepsin-sensitive linker. Furthermore, we suggest that the peptide design strategy should incorporate population-specific HLA alleles in order to optimize binding specificity of the peptides. We refer to this as populationalized vaccinomics.

Abstract: Systemic inflammatory response syndrome (SIRS) is a clinical diagnosis based on abnormalities in patients' vital signs and white blood cell count. Neutrophil-lymphocyte ratio (NLR) is used as an easily accessible parameter to assess the patient's inflammatory status and stress. There are some studies showing that NLR affected by the inflammatory response is a criterion to support the diagnosis of SIRS. In this study, it was aimed to compare the interrelation between SIRS (+) and SIRS (-) groups in patients with high positive feline coronavirus (FCoV) in the light of NLR. Based on the anamneses, physical examination findings, laboratory findings, enzyme immunoassay antibody test kit titer were included in the sick groups. These patients were further categorized based on the presence of SIRS symptoms, vital signs and laboratory findings. The NLR as diagnostic marker demonstrated to differ between high antibody titer FCoV positive and healthy cats. However the diagnostic significance of NLR remains questionable between the high antibody titer FCoV positive cats with SIRS (+) and SIRS (-). As a result of our study NLR can be used as a blood parameter like albumin/globulin ratio and elevated total bilirubin in cats with high FCoV antibody titer and high probability of developing FIP.

To better understand the genes with altered expression caused by infection with the novel coronavirus strain SARS-CoV-2 causing COVID-19 infectious disease, a tensor decomposition (TD)-based unsupervised feature extraction (FE) approach was applied to a gene expression profile dataset of the mouse liver and spleen with experimental infection of mouse hepatitis virus, which is regarded as a suitable model of human coronavirus infection. TD-based unsupervised FE selected 134 altered genes, which were enriched in protein-protein interactions with orf1ab, polyprotein, and 3C-like protease that are well known to play critical roles in coronavirus infection, suggesting that these 134 genes can represent the coronavirus infectious process. We then selected compounds targeting the expression of the 134 selected genes based on a public domain database. The identified drug compounds were mainly related to known antiviral drugs, several of which were also included in those previously screened with an in silico method to identify candidate drugs for treating COVID-19.

A new coronavirus (SARS-CoV-2) have determined a pneumonia outbreak in China (Wuhan and Hubei) on December 2019. While pharmaceutical and non-pharmaceutical intervention strategies are strengthened worldwide, the scientific community has been studying the risk factors associated with SARS-Cov-2, to enrich epidemiological information. For a long time, before the industrialized era, air pollution has been a real and big health concern and it is today a very serious environmental risk for many diseases and anticipated deaths in the world. It has long been known that air pollutants increasing the invasiveness of pathogens for humans by acting as a carrier and making people more sensitive to pathogens through a negative influence on the immune system. Based on scientific evidences, the hypothesis that air pollution, resulting from a combination of factors such as meteorological data, level of industrialization as well as regional topography, can acts both as an infection carrier as a harmful factor of the health outcomes of COVID-19 disease has been raised recently. This hypothesis is turning in scientific evidence, thanks to the numerous studies that have been launched all over the world. With this review, we want to provide a first unique view of all the first epidemiological studies relating the association between air pollution and SARS-CoV-2. Major findings are consistent, highlighting the important contribution of air pollution on the COVID-19 spread and with a less extent also PM₁₀.

Covid-19 infections are rapidly spreading worldwide with more than 100000 death and thus understanding the molecular mechanism of tropism of human cells is an urgent need for drug design. We have described here a bioinformatics approach to predict the functional aspects of non-structural nsp16 protein of Corona virus. The covid-19 7098 AA large polyprotein was degraded into sixteen proteins and last nsp16 protein was found an RlmE type rRNA methyltransferase. Nsp16 has no similarity to bacterial RlmABCD but has 25 percent similarity to the bacterial RlmE protein which methylates the U2551 2-hydroxy group of Ribose. The nsp16 proteins of different corona viruses like covid-19, bat-coronavirus, SARS and MERS have strong homology. Mrm2 and Dim1 like yeast and mammalian rRNA methyltransferases have 26-33 percent homologies but not with 2-O-capping MTase as reported previously. Rrp8 MTases also has no similarity to nsp16. We postulated that mitochondrial rRNA methylation of bronchial cells were mediated by the nsp16 protein causing inhibition of protein synthesis due to poor assembly of aminoacyl-tRNA or mRNA and peptidyl transferase at the PTC. This is one of the new molecular mechanism of corona virus cellular tropism and different than ACE-2 mediated blockage of cellular signalling to inhibit aldesterone biosynthesis with abnormal Na⁺ ions in cells. We also designed primers based on nsp16 cDNA sequence (nt 20659-21552, accession no MT121215) specific for Covid-19 diagnosis by RT-PCR.

Bovine coronavirus (BCoV) is one of the most common pathogens affecting cattle of all ages. BCoV possesses multiple tissue tropism in cattle, particularly in the respiratory and enteric tracts of the affected animals. Viral entry is a crucial step in the replication cycle of all viruses, including BCoV. The process of viral entry requires the orchestration between several proteins from the virus and the host side. The coronavirus spike glycoproteins contributed substantially to other viral infections and the molecular pathogenesis of coronaviruses, including BCoV. Meanwhile, among all corona-viruses, the hemagglutinin esterase enzyme is found in only BCoV and the human corona-virus-OC43 (HCoV-OC43). The viral receptors are among the key players in the viral entry and could explain the viral tropism, at least in part. The presence of some host cell proteases also en-hances the virus replication from the entry until the release of the virus from the host cells. Previous studies have shown that the 9- O-acetylated sialic acids could potentially act as receptors for the BCoV. However, little is known about the BCoV receptors and if other co/receptors might be needed to ensure viral entry to the host cells. In addition to that, the roles of other host cell proteases, such as Furin and TMPRSS2, in BCoV infection have not yet been well studied. The main objectives of the current study are to identify some novel receptors for BCoV and some host cell proteases that might enhance virus replication. We used some in silico docking tools to predict some new BCoV receptors out of some known other coronavirus receptors (ACE-2, NRP1, DPP4, APN, and CEACAM1). Our results postulated the potential actions of the host Furin and TMPRRS2 enzymes in the activation of BCoV-S glycoprotein, which potentially enhances BCoV replication. Our modeling confirms the high binding affinities of both the 9- O-acetylated sialic and the NRP1 with the BCoV-S and BCoV-HE compared to the ACE-2, DPP4, and CEACAM-1, suggesting their roles as receptors for BCoV. Our prediction models show the potential bindings of the Furin and TMPRSS2 to the BCoV-S polybasic cleavage site (RRSRR|A). To our knowledge, this is the first study to investigate the bovine coronavirus interaction with some other potential host receptors, particularly ACE-2, NRP1, DPP4, APN and CEACAM1, TMPRSS2, and the bovine Furin protease.

Aims: Angiotensin-converting enzyme 2 (ACE2) plays an important role in the entry of coronaviruses into host cells. This paper described how carnosine, a naturally occurring supplement, can be an effective drug candidate for coronavirus disease (COVID-19) on the basis of molecular docking and modeling to host ACE2 co-crystallized with COVID-19 spike protein. Methods: First, the starting point was ACE2 inhibitors and their structure-activity relationship (SAR). Next, chemical similarity (or diversity) and PubMed searches made it possible to repurpose and assess approved or experimental drugs for COVID-19. In parallel, at all stages, authors performed bioactivity scoring to assess potential repurposed inhibitors at ACE2. Finally, investigators performed molecular docking and modeling of the identified drug candidate to host ACE2 co-crystallized with COVID-19 spike protein. Results: Carnosine emerged as the best known drug candidate to match ACE2 inhibitor structure. Preliminary docking was more optimal to ACE2 than the known typical angiotensin-converting enzyme 1 (ACE1) inhibitor (enalapril) and quite comparable to known or presumed ACE2 inhibitors. Viral spike protein elements binding to ACE2 were retained in the best carnosine pose in SwissDock at 1.75 Angstroms. Out of the three main areas of attachment expected to the co-crystallized protein structure, carnosine bind with higher affinity to two compared to the known ACE2 active site. LibDock score was 92.40 for site 3, 90.88 for site 1, and inside the active site 85.49. Conclusion: Carnosine has promising inhibitory interactions with host ACE2 co-crystallized with COVID-19 spike protein and hence could offer potential mitigating effect against current COVID-19 pandemic.

Background and Objectives: The trends in metabolic dysfunction-associated steatotic liver disease (MASLD) and related metabolic dysfunctions in Japan is unknown. Thus, we aimed to clarify the trends of these before the novel coronavirus disease 2019 pandemic in Japan. Materials and Methods: We included Japanese individuals aged 25-79 years who underwent health examinations at our center. We analyzed anthropometry, lifestyle-related disease, and nutritional intake in relation to MASLD trends from 2010-2019. Results: The prevalence of MASLD increased in all ages and body mass index (BMI) classes, reaching 30.3% in males and 16.1% in females, with MASLD accounting for 75% of steatotic liver cases and more than half of all type 2 diabetes mellitus (T2DM) and high waist circumference (HWC) cases. The increase in the prevalence of MASLD was due to an increase in that of steatotic liver itself, and there was no increase in the prevalence of other factors, such as overweight, T2DM, hypertension, and dyslipidemia. The prevalence of glucose metabolic disorders (GMDs) and hypertension decreased. National nutritional data showed an increase in energy intake, total fat, saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids, which correlated with a decrease in GMDs. Salt intake also decreased, which correlated with hypertension. The MASLD group had a higher prevalence of all related metabolic factors than the non-MASLD group, especially HWC, T2DM, and hyperlipidemia. Conclusion: The prevalence of MASLD increased with that of steatotic liver, regardless of age or BMI. A relationship between increased dietary fat, increased steatotic liver, and decreased GMDs was suggested.