Since late 2019, Coronavirus Disease 2019 (COVID-19) has spread all over the world. The disease is highly contagious, and it may lead to acute respiratory distress (ARD). Medical imaging can play an important role in classifying, detecting, and measuring the severity of the virus. This study aims to provide a novel auto-detection tool that can detect abnormal changes in conventional X-ray images for confirmed COVID-19 cases. X-ray images from patients diagnosed with COVID-19 were converted into 19 different colored layers. Each layer represented objects with similar contrast that could be defined as a specific color. The objects with similar contrasts were formed in a single layer. All the objects from all the layers were extracted as a single-color image. Based on the differentiation of colors, the prototype model was able to recognize a wide spectrum of abnormal changes in the image texture. This was true even if there was minimal variation of the contrast values of the detected uncleared abnormalities. The results indicate that the proposed novel method can detect and determine the degree of lung infection from COVID-19 with an accuracy of 91%, compared to the opinions of three experienced radiologists. The method can also efficiently determine the sites of infection and the severity of the disease by classifying the X-rays into five levels of severity. Thus, the proposed COVID-19 autodetection method can identify locations and indicate the degree of severity of the disease by comparing affected tissue with healthy tissue, and it can predict where the disease may spread.

OBJECTIVE To investigate the relation between COVID-19 vaccine coverage and COVID-19-related mortality by age groups in Brazil in 2021. METHODS Secondary data on COVID-19 deaths and vaccination coverage were retrieved to investigate COVID-19 mortality rate (MR) evolution as the vaccination against COVID-19 advanced in Brazil in 2021. Poisson regression with adjustment for age and Brazilian states was used to calculate the MR. RESULTS By mid-April 2021, MR increased 2 - 3 times compared with the already high level in January for people aged 60 years or older, reaching the highest epidemic level of 5 - 15 per 100,000 inhabitants in this age group. Despite the following decline trend, by the end of May, the MR level was still about 50% and 80% higher for the age groups of 40 - 79 years and 80 years or older. The coverage concerning the first dose of COVID-19 vaccine reached 80% for people aged 60 - 69 years and exceeded 95% for those aged 70 years or older, but the second dose was only given to 26, 76 and 64% of the age groups of 60 - 69, 70 - 79, and 80 years or older, respectively. The age-standardized average MR over the study period was the highest in northern Brazilian states of Rond?nia, Amazonas, Acre, and Roraima (range 6-8.4 per 100,000 inhabitants). CONCLUSIONS COVID-19 vaccination coverage was below the level necessary to protect Brazilians from rising MR between January and May 2021. Urgent measures are necessary to increase the vaccine supply and the adherence to non-pharmacological protective measures.

BACKGROUND: Guidelines recommend that patients with haemophilia should preferably receive vaccination subcutaneously. COVID-19 and other vaccines, however, are only licenced for intramuscular application. AIMS: To assess the safety of intramuscular COVID-19 vaccination in patients living with haemophilia. METHODS: Part A of this prospective observational study enrolled consecutive patients with haemophilia A (HA) and B (HB) of all ages and severities and assessed injection site bleeding and other complications within 30 days of vaccination. Part B enrolled patients providing informed consent for detailed data collection including medication and prophylaxis around the time of vaccination. Logistic regression was performed to assess potential risk factors for bleeding. RESULTS: Four hundred and sixty-one patients were enrolled into part A. The primary endpoint injection site bleeding occurred in seven patients (1.5%, 95% confidence interval .7-3.1%). Comprehensive analysis of 214 patients (404 vaccinations, part B) revealed that 97% of patients with severe haemophilia had prophylaxis before vaccination, either as part of their routine prophylaxis or using additional doses. 56% and 30% of patients with moderate and mild haemophilia, respectively, received prophylaxis before vaccination. Among the seven bleeds recorded, three occurred when intramuscular vaccination was done without prophylaxis (odds ratio 12). CONCLUSIONS: This is the first prospective study reporting on the safety of intramuscular vaccination in haemophilia. The rate of injection site bleeding was low in mild haemophilia, and in moderate and severe haemophilia if patients received factor prophylaxis.

Aim: In view of the spread of the contagious coronavirus disease (COVID-19) globally, the present review focuses on the details of past pandemic diseases, along with comparisons and lessons learned. A general awareness of COVID-19 infection is addressed, and it is compared with the Spanish flu pandemic. Based on the successes, failures and lessons learned in the past, governmental efforts must be undertaken to empower citizens by providing accurate information and implementing post-COVID-19 precautions that need to be taken now to stop the spread and recurrence of the virus locally, and to restore health and economic normalcy. Methods: A detailed literature survey of past pandemics is undertaken in order to extract the successes, failures and lessons learned from previous breakouts. The comparison of past pandemics will enable us to determine post-COVID-19 precautions that should be followed. Separate tables are prepared to highlight the lessons learned and measures to be taken. Both general precautions and preventive measures for pregnant women are compiled. Results: The literature shows a continuous struggle of humans with disease outbreaks, with the most adverse impact of the Spanish flu killing 20-50 million people. Precautions need to be taken including social distancing, compulsory mask-wearing, avoiding public gatherings and washing hands regularly. The lessons from earlier pandemics show that they were equally devastating, and vaccines were not available at the time of outbreaks. Vaccines developed for polio, H1N1, measles, and other viral diseases have proven to save countless lives. Living with COVID-19 and evolving the work culture of protecting oneself and protecting others also has to be adopted. Conclusions: COVID-19 has become an everyday topic of discussion throughout the world, indicating the increasing number of COVID-19 cases, deaths and recoveries. The lessons learned from past pandemics such as social distancing, wearing masks, avoiding public gatherings and adherence to guidelines, along with personal hygiene, are the key measures that must be taken in order to live with COVID-19. Precautions for the elderly and pregnant women advised by medical authorities are to be strictly adhered to. These will help in reducing COVID-19 cases and in turn will reduce the pressure on hospitals to serve those in need. India has learned lessons from the past and the present pandemic and will move towards growth through its self-reliance.

[Image: see text] Two proteases produced by the SARS-CoV-2 virus, the main protease and papain-like protease, are essential for viral replication and have become the focus of drug development programs for treatment of COVID-19. We screened a highly focused library of compounds containing covalent warheads designed to target cysteine proteases to identify new lead scaffolds for both M(pro) and PL(pro) proteases. These efforts identified a small number of hits for the M(pro) protease and no viable hits for the PL(pro) protease. Of the M(pro) hits identified as inhibitors of the purified recombinant protease, only two compounds inhibited viral infectivity in cellular infection assays. However, we observed a substantial drop in antiviral potency upon expression of TMPRSS2, a transmembrane serine protease that acts in an alternative viral entry pathway to the lysosomal cathepsins. This loss of potency is explained by the fact that our lead M(pro) inhibitors are also potent inhibitors of host cell cysteine cathepsins. To determine if this is a general property of M(pro) inhibitors, we evaluated several recently reported compounds and found that they are also effective inhibitors of purified human cathepsins L and B and showed similar loss in activity in cells expressing TMPRSS2. Our results highlight the challenges of targeting M(pro) and PL(pro) proteases and demonstrate the need to carefully assess selectivity of SARS-CoV-2 protease inhibitors to prevent clinical advancement of compounds that function through inhibition of a redundant viral entry pathway.

The COVID-19 pandemic caused by SARS-CoV-2 has infected millions worldwide, therefore there is an urgent need to increase our diagnostic capacity to identify infected cases. Although RT-qPCR remains the gold standard for SARS-CoV-2 detection, this method requires specialised equipment in a diagnostic laboratory and has a long turn-around time to process the samples. To address this, several groups have recently reported the development of loop-mediated isothermal amplification (LAMP) as a simple, low cost and rapid method for SARS-CoV-2 detection. Herein we present a comparative analysis of three LAMP-based assays that target different regions of the SARS-CoV-2: ORF1ab RdRP, ORF1ab nsp3 and Gene N. We perform a detailed assessment of their sensitivity, kinetics and false positive rates for SARS-CoV-2 diagnostics in LAMP or RT-LAMP reactions, using colorimetric or fluorescent detection. Our results independently validate that all three assays can detect SARS-CoV-2 in 30 min, with robust accuracy at detecting as little as 1000 RNA copies and the results can be visualised simply by color changes. Incorporation of RT-LAMP with fluorescent detection further increases the detection sensitivity to as little as 100 RNA copies. We also note the shortcomings of some LAMP-based assays, including variable results with shorter reaction time or lower load of SARS-CoV-2, and false positive results in some experimental conditions and clinical saliva samples. Overall for RT-LAMP detection, the ORF1ab RdRP and ORF1ab nsp3 assays have faster kinetics for detection but varying degrees of false positives detection, whereas the Gene N assay exhibits no false positives in 30 min reaction time, which highlights the importance of optimal primer design to minimise false-positives in RT-LAMP. This study provides validation of the performance of LAMP-based assays as a rapid, highly sensitive detection method for SARS-CoV-2, which have important implications in development of point-of-care diagnostics for SARS-CoV-2.

Introduction The COVID-19 is a highly contagious disease belonging to the family of coronaviruses which can affect a great deal of people shortly. As a devastating event in the world, many people suffer the PTSD from this severe disease. The aim of study is to explore the prevalence and severity of post-traumatic stress disorder (PTSD) symptoms, and discuss the possible factors among the general public in China after the COVID-19 epidemic outbreak. Methods This is a cross-sectional study. We used the self-designed demographic questionnaire and the Posttraumatic Stress Checklist-Civilian Version (PCL-C) of Chinese version as our screening tools to investigate 4872 subjects living in the communities in China from Nov. 8th, 2020 to Dec. 8th, 2020. Results Finally, we received 3705 effective respondents. The response rates of the questionnaire can reach 76.97 percentage. Peculiarly, the prevalence of PTSD mild and severe symptoms after the COVID-19 epidemic outbreak was 53.2%. Mild PTSD symptoms accounted for 24.9%, and severe PTSD symptoms (scores above 38) accounted for 28.3%. PCL-C mean scores were 41.414.7. The females accounted for 67.7% of the total samples. Participants mean age was 30.511.2 years old. The PCL-C gross scores of females were all higher than males in four subject groups. Meantime, gender and age made differences not only in total PCL-C points but also in the four aspects of PCL-C (P<0.001). The middle-aged group (ages from 45 to 60) got the lowest scores among the four groups. Conclusion COVID-19 brought tremendous psychological pressure on the public in many ways, including peoples work, social contact, study, and daily life. Results of our research discover that symptoms of the PTSD are severe, including the re-experiencing, avoidance/numbing, flashbacks, and hyper-arousal. Actions should be taken at society level to prevent and protect individuals from PTSD suffering. Special attention should be paid to females and young people. Further studies should be conducted to explore the dynamic and other risk and protection factors to prevent PTSD.

Introduction Outcomes related to Covid-19 in systemic sclerosis patients could be influenced by internal organ involvement and/or immunosuppressive treatment, leading to efforts to shield patients from Covid-19 transmission. We examined the impact of Covid-19 on the lived experience of systemic sclerosis with regards to other aspects of daily living including occupation and emotional well-being. Method Individuals with systemic sclerosis or relatives/carers participated in an online survey, disseminated through international patient associations and social media pages, designed to examine the impact of Covid-19 on living with a rare disease. Results Responses from 121 individuals (98% were patients with systemic sclerosis) from 14 countries were evaluable. Covid-19 was considered a probable/definite personal threat (93%) or threat for the individual they care for (100%). Approximately two-thirds of responders reported either cancellation or postponement/delay to appointments, diagnostic tests, medical therapies at home (e.g. infusions), surgery or transplant, psychiatry follow-up or rehabilitation services. Twenty-six percent reported at least one systemic sclerosis medicine/treatment had been unavailable, and 6% had to either stop taking usual medications or use an alternative. Most reported online consultations/telemedicine via phone (88%) and online (96%) as being 'fairly' or 'very' useful. Respondents reported tensions among family members (45%) and difficulty overcoming problems (48%). Restrictions on movement left around two-thirds feeling isolated (61%), unhappy and/or depressed (64%), although the majority (85%) reported a strengthening of the family unit. Conclusion Covid-19 has resulted in significant impact on the clinical-care and emotional well-being of systemic sclerosis patients. Changes to clinical care delivery have been well-received by patients including telemedicine consultations.

In the present article we present an update on the role of chemoprevention and other pharmacological activities reported on kurarinone, a natural flavanone (from 1970 to 2021). To the best of our knowledge this is the first and exhaustive review of kurarinone. The literature was obtained from different search engine platforms including PubMed. Kurarinone possesses anticancer potential against cervical, lung (non-small and small), hepatic, esophageal, breast, gastric, cervical, and prostate cancer cells. In vivo anticancer potential of kurarinone has been extensively studied in lungs (non-small and small) using experimental xenograft models. In in vitro anticancer studies, kurarinone showed IC(50) in the range of 2C62 M while in vivo efficacy was studied in the range of 20C500 mg/kg body weight of the experimental organism. The phytochemical showed higher selectivity toward cancer cells in comparison to respective normal cells. kurarinone inhibits cell cycle progression in G2/M and Sub-G1 phase in a cancer-specific context. It induces apoptosis in cancer cells by modulating molecular players involved in apoptosis/anti-apoptotic processes such as NF-B, caspase 3/8/9/12, Bcl2, Bcl-XL, etc. The phytochemical inhibits metastasis in cancer cells by modulating the protein expression of Vimentin, N-cadherin, E-cadherin, MMP2, MMP3, and MMP9. It produces a cytostatic effect by modulating p21, p27, Cyclin D1, and Cyclin A proteins in cancer cells. Kurarinone possesses stress-mediated anticancer activity and modulates STAT3 and Akt pathways. Besides, the literature showed that kurarinone possesses anti-inflammatory, anti-drug resistance, anti-microbial (fungal, yeast, bacteria, and Coronavirus), channel and transporter modulation, neuroprotection, and estrogenic activities as well as tyrosinase/diacylglycerol acyltransferase/glucosidase/aldose reductase/human carboxylesterases 2 inhibitory potential. Kurarinone also showed therapeutic potential in the clinical study. Further, we also discussed the isolation, bioavailability, metabolism, and toxicity of Kurarinone in experimental models.

Sam Foster, Chief Nurse, Oxford University Hospitals, describes the problems faced by trusts as they attempt to limit the risks faced by employees returning to the workplace as the coronavirus lockdown eases.

Multiloop scattering amplitudes describing the quantum fluctuations at high-energy scattering processes are the main bottleneck in perturbative quantum field theory. The loop-tree duality is a novel method aimed at overcoming this bottleneck by opening the loop amplitudes into trees and combining them at integrand level with the real-emission matrix elements. In this Letter, we generalize the loop-tree duality to all orders in the perturbative expansion by using the complex Lorentz-covariant prescription of the original one-loop formulation. We introduce a series of mutiloop topologies with arbitrary internal configurations and derive very compact and factorizable expressions of their open-to-trees representation in the loop-tree duality formalism. Furthermore, these expressions are entirely independent at integrand level of the initial assignments of momentum flows in the Feynman representation and remarkably free of noncausal singularities. These properties, that we conjecture to hold to other topologies at all orders, provide integrand representations of scattering amplitudes that exhibit manifest causal singular structures and better numerical stability than in other representations.

On February 19th 2020, the Iranian Ministry of Health and Medical Education (MoHME) has announced the first 2 cases of SARS-CoV-2, a novel emerging coronavirus which causes an infection termed as COVID-19, in Qom city. As such, the Iranian government, through the establishment of the "National Headquarters for the management and control of the novel Coronavirus", has started implementing policies and programs for the prevention and control of the virus. These measures include schools and universities closure, reduced working hours, and increased production and delivery of equipment such as masks, gloves and hygienic materials for sterile environments. The government has also made efforts to divulge high-quality information concerning the COVID-19 and to provide laboratories and hospitals with diagnostic kits and adequate resources to treat patients. However, despite such efforts, the number of cases and deaths has progressively increased with rising trends in total confirmed cases and deaths, as well as in new daily cases and deaths associated with the COVID-19. Iran is a developing country and its economic infrastructure has been hit hardly by embargo and sanctions. While developed countries have allocated appropriate funding and are responding adequately to the COVID-19 pandemics, Iran has experienced a serious surge of cases and deaths and should strive to provide additional resources to the health system to make healthcare services more accessible and to increase the fairness of that access. All relevant actors and stakeholders should work together to fight this disease.

The pandemic caused by the novel Coronavirus SARS-CoV2 has been responsible for life threatening health complications, and extreme pressure on healthcare systems. While preventive and definite curative medical interventions are yet to arrive, Non-Pharmaceutical Interventions (NPIs) like physical isolation, quarantine and drastic social measures imposed by governing agencies are effective in arresting the spread of infections in a population. In densely populated countries like India, lockdown interventions are partially effective due to social and administrative complexities. Using detailed demographic data, we present an agent based model to imitate the behavior of the population and its mobility features, even under intervention. We demonstrate the effectiveness of contact tracing policies and how our model efficiently relates to empirical findings on testing efficiency. We also present various lockdown intervention strategies for mitigation - using the bare number of infections, the effective reproduction rate, as well as using reinforcement learning. Our analysis can help assess the socio-economic consequences of such interventions, and provide useful ideas and insights to policy makers for better decision making.

The spike glycoprotein (S-protein) mediates SARS-CoV-2 entry via intermolecular interaction with human angiotensin-converting enzyme 2. The receptor binding domain (RBD) of the S-protein has been considered critical for this interaction and acts as the target of numerous neutralizing antibodies and antiviral peptides. This study used the fragment molecular orbital method to analyze the interactions between the RBD and antibodies/peptides and extracted crucial residues that can be used as epitopes. The interactions evaluated as interfragment interaction energy values between the RBD and 12 antibodies/peptides showed a fairly good correlation with the experimental activity pIC50 (R2 = 0.540). Nine residues (T415, K417, Y421, F456, A475, F486, N487, N501, and Y505) were confirmed as being crucial. Pair interaction energy decomposition analyses showed that hydrogen bonds, electrostatic interactions, and &#960;-orbital interactions are important. Our results provide essential information for understanding SARS-CoV-2-antibody/peptide binding and may play roles in future antibody/antiviral drug design.

Background: Structured reporting (SR) in radiology is becoming necessary and has recently been recognized by major scientific societies. This study aimed to build CT-based structured reports for lung cancer during the staging phase, in order to improve communication between radiologists, members of the multidisciplinary team and patients. Materials and Methods: A panel of expert radiologists, members of the Italian Society of Medical and Interventional Radiology, was established. A modified Delphi exercise was used to build the structural report and to assess the level of agreement for all the report sections. The Cronbachs alpha (C) correlation coefficient was used to assess internal consistency for each section and to perform a quality analysis according to the average inter-item correlation. Results: The final SR version was built by including 16 items in the Patient Clinical Data section, 4 items in the Clinical Evaluation section, 8 items in the Exam Technique section, 22 items in the Report section, and 5 items in the Conclusion section. Overall, 55 items were included in the final version of the SR. The overall mean of the scores of the experts and the sum of scores for the structured report were 4.5 (range 1C5) and 631 (mean value 67.54, STD 7.53), respectively, in the first round. The items of the structured report with higher accordance in the first round were primary lesion features, lymph nodes, metastasis and conclusions. The overall mean of the scores of the experts and the sum of scores for staging in the structured report were 4.7 (range 4C5) and 807 (mean value 70.11, STD 4.81), respectively, in the second round. The Cronbachs alpha (C) correlation coefficient was 0.89 in the first round and 0.92 in the second round for staging in the structured report. Conclusions: The wide implementation of SR is critical for providing referring physicians and patients with the best quality of service, and for providing researchers with the best quality of data in the context of the big data exploitation of the available clinical data. Implementation is complex, requiring mature technology to successfully address pending user-friendliness, organizational and interoperability challenges.

Our research aims to establish an evaluation framework and evaluate the sustainability of scientific research in universities. Based on the concept of Education for Sustainable Development and the function of scientific research activities, an evaluation framework was constructed including three dimensions: the sustainable trend of scientific research activity, research performance related to the topic of sustainable development, and sustainability of scientific research contributions. Descriptive analysis, Data Envelopment Analysis, and a Statistical Index Method were used to calculate the sustainability of scientific research of world-class universities in China. Results show that Chinas world-class universities published more articles related to sustainable development than the best-performing universities in the UK and USA. They make sustainable contributions to society through cultivating Ph.D. graduates, publishing research papers, and transforming science and technology. However, the sustainable trend of the scientific research of universities is still to be improved. The result of resource efficiency is relatively low, and attention should be paid to the waste of human and financial resources. In addition, universities should improve their ability to withstand external risks to minimize the influence of external public emergencies such as COVID-19.

Autoimmune blistering diseases (AIBD) are often treated with immunosuppressive medications, including rituximab, yet the implications of these approaches during the COVID-19 pandemic are not fully understood. COVID-19 outcome studies in AIBD patients are limited by small sample sizes and interpretation complicated by advanced ages and comorbidities common in this population.

About a year into the pandemic, COVID-19 accumulates more than two million deaths worldwide. Despite non-pharmaceutical interventions such as social distance, mask-wearing, and restrictive lockdown, the daily confirmed cases remain growing. Vaccine developments from Pfizer, Moderna, and Gamaleya Institute reach more than 90% efficacy and sustain the vaccination campaigns in multiple countries. However, natural and vaccine-induced immunity responses remain poorly understood. There are great expectations, but the new SARS-CoV-2 variants demand to inquire if the vaccines will be highly protective or induce permanent immunity. Further, in the first quarter of 2021, vaccine supply is scarce. Consequently, some countries that are applying the Pfizer vaccine will delay its second required dose. Likewise, logistic supply, economic and political implications impose a set of grand challenges to develop vaccination policies. Therefore, health decision-makers require tools to evaluate hypothetical scenarios and evaluate admissible responses. Following some of the WHO-SAGE recommendations, we formulate an optimal control problem with mixed constraints to describe vaccination schedules. Our solution identifies vaccination policies that minimize the burden of COVID-19 quantified by the number of disability-adjusted years of life lost. These optimal policies ensure the vaccination coverage of a prescribed population fraction in a given time horizon and preserve hospitalization occupancy below a risk level. We explore "via simulation" plausible scenarios regarding efficacy, coverage, vaccine-induced, and natural immunity. Our simulations suggest that response regarding vaccine-induced immunity and reinfection periods would play a dominant role in mitigating COVID-19.

The ability to deliver therapeutics sitespecifically in vivoremains a major challenge for the treatment of malignant, inflammatory, cardiovascular, and degenerative diseases. The need to target agents safely, efficiently, and selectively has become increasingly evident because of progress in vascular targeting. The vascular endothelium is a central target for intervention, given its multiple roles in the physiology (in health) and pathophysiology (in disease) and its direct accessibility to circulating ligands. In cancer, the expression of specific molecules on the surface of vascular endothelial and perivascular cells might enable direct therapeutic targeting. The use of in vivo phage display has significantly contributed to the identification of such targets, which have been successfully used for directed vascular targeting in preclinical animal models. Several animal studies have been performed by using fused molecules between tumor endothelium-directed molecules and immunomodulatory, procoagulant, or cytotoxic molecules. In addition to delivery of therapeutic agents, vascular targeted gene therapies based on both ligand-directed delivery of gene vectors to tumor endothelium and transcriptional targeting have also emerged. In this review, we discuss ligand-directed vascular targeting strategies with an emphasis on recent developments related to phage-display-based screenings.

OBJECTIVE. The purpose of this study is to evaluate the potential benefit of spectral imaging, notably electron density imaging, in patients with suspected or confirmed coronavirus disease (COVID-19), by retrospectively reviewing the cases of four patients who each underwent two chest CT scans for confirmed COVID-19. CONCLUSION. The use of spectral CT with electron density imaging could improve the assessment of lung lesion extent in patients with early-stage COVID-19.