To explore the intramolecular interactions of protein, and its folding and unfolding mechanisms, we performed a simulation-based comparative study on albumin at different ionic strengths and pH. In this study, we performed molecular dynamics (MD) simulation for bovine serum albumin (BSA) at five different concentrations of NaCl (10, 20, 30, 40 and 50 mM), and five different pH values (2.0, 3.5, 4.3, 7.4, and 9.0). Herein, our aim was to unravel the effects of both pH and ionic strength on the conformations of the serum albumin structure. Our results indicate the effects of physicochemical factors in promoting conformational changes in the albumin structure, unlocking the hydrophobic sequences for hydrophobic drug binding. The BSA structure showed similarity to its native state in the pH range of 4.5 to 7.4 and at various ionic concentrations of NaCl. In the pH range of 3.5 to 4.5, the BSA structure showed denaturation in a controlled manner, which caused significant conformational changes in the molecular position of its hydrophobic amino acid residues. The resultant 3D structure gives insight into the amino acid trajectories. High denaturation and unstable behavior in the structural and conformational changes of the protein structure were observed at pH 2.0 and pH 9.0. We believe that these results and conditions will be helpful in the development of protein-based universal nanocarriers for the encapsulation of both hydrophilic and hydrophobic drugs.

The influence of human-care service robots in humanCrobot interaction is becoming of great importance, because of the roles that the robots are taking in todays and future society. Thus, we need to identify how humans can interact, collaborate, and learn from social robots more efficiently. Additionally, it is important to determine the robots modalities that can increase the humans perceived likeness and knowledge acquisition and enhance humanCrobot collaboration. The present study aims to identify the optimal social service robots modalities that enhance the human learning process and level of enjoyment from the interaction and even attract the humans attention to choosing a robot to collaborate with it. Our target group was college students, pre-service teachers. For this purpose, we designed two experiments, each one split in two parts. Both the experiments were between groups, and human participants had the chance to watch the Nao robot performing a storytelling exercise about the history of robots in a museum-educational activity via video annotations. The robots modalities were manipulated on its body movements (expressive arm and head gestures) while performing the storytelling, friendly attitude expressions and storytelling, and personality traits. After the robots storytelling, participants filled out a knowledge acquisition questionnaire and a self-reported enjoyment level questionnaire. In the second part, we introduce the idea of participants witnessing a conversation between the robots with the different modalities, and they were asked to choose the robot with which they want to collaborate in a similar activity. Results indicated that participants prefer to collaborate with robots with a cheerful personality and expressive body movements. Especially when they were asked to choose between two robots that were cheerful and had expressive body movements, they preferred the one which originally told them the story. Moreover, participants did not prefer to collaborate with a robot with an extremely friendly attitude and storytelling style.

AIM: Restarting elective services presents a challenge to restore and improve many of the planned patient care pathways which have been suspended during the response to the COVID-19 pandemic. A significant backlog of planned elective work has built up representing a considerable volume of patient need. We aimed to investigate the health status, quality of life, and the impact of delay for patients whose referrals and treatment for symptomatic joint arthritis had been delayed as a result of the response to COVID-19. METHODS: We interviewed 111 patients referred to our elective outpatient service and whose first appointments had been cancelled as a result of the response to the COVID-19 pandemic. RESULTS: Patients reported significant impacts on their health status and quality of life. Overall, 79 (71.2%) patients reported a further deterioration in their condition while waiting, with seven (6.3%) evaluating their health status as worse than death. CONCLUSIONS: Waiting lists are clearly not benign and how to prioritize patients, their level of need, and access to assessment and treatment must be more sophisticated than simply relying on the length of time a patient has been waiting. This paper supports the contention that patients awaiting elective joint arthroplasty report significant impacts on their quality of life and health status. This should be given appropriate weight when patients are prioritized for surgery as part of the recovery of services following the COVID-19 pandemic. Elective surgery should not be seen as optional surgerypatients do not see it in this way.

Objectives It is a concern that public health measures to prevent older people contracting COVID-19 could lead to a rise in mental health problems such as depression. The aim of this study therefore is to examinetrends of depressive symptomsbefore and during the COVID-19 pandemic in a large cohort of older people. Design Observational study with 6-year follow-up. Setting& Participants Over 3,000 community-dwelling adults aged 60 yearsparticipating in The Irish Longitudinal Study on Ageing (TILDA). Methods Mixed-effects multilevel models were used to describe trends in depressive symptoms across 3 waves of TILDA; Waves 4 (2016), 5 (2018) and a final wave conductedJuly-November 2020. Depressive symptoms were measured using 8-item CES-D, a score 9 indicating clinically significant symptoms. Results The prevalence of clinically significant depressive symptoms at Waves 4 and 5 was 7.2% (6.5C7.9) and 7.2% (6.5C8.0) respectively. This more than doubled to 19.8% (18.5C21.2) during the COVID-19 pandemic. There was no change in CES-D scores between Waves 4 and 5 (=0.09 (-0.04 C 0.23) but a large increase in symptoms was observed during the pandemic (=2.20 (2.07C2.33)). Age 70 years was independently associated with depressive symptoms (=0.45 (0.18C0.72)) during the pandemic but notfrom Wave 4 to 5 (=0.09 (-0.18C0.36)). Living with others was associated with lower burden of symptoms during the pandemic (=-0.40 (-0.71 - -0.09)) but not between Waves 4 and 5 (=-0.40 (-0.71 - -0.09)). Conclusions& Implications This study demonstrates significant increases in the burden of depressive symptoms amongst older people during the COVID-19 pandemic, particularly those aged 70 years and/or living alone. Even a small increase in the incidence of late life depression can have major implications for healthcare systems and societies in general. Improving access to age-attuned mental health care should therefore be a priority.

This short report describes the development of a COVID-19 module for Round 10 of the European Social Survey (ESS). The module is formed of 20 items, including 10 agreed with ESS National Coordinators and 10 developed by two academic teams following an external call for content. The majority of ESS participating countries will field the module for Round 10 fieldwork in 2020C2021. This report provides the rationale for the module, presents challenges of developing such a module for ESS, and gives an overview of the question development and testing process. The two external sub-modulesGovernment authority and legitimacy in the age of a pandemic and COVID-19 conspiracy beliefs and government rule complianceare also introduced. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s42409-021-00029-4.

Coronavirus Disease-2019 (COVID-19) is an infectious disease caused by the SARS-CoV-2 virus. It was first identified in Wuhan, China, and has since spread causing a global pandemic. Various studies have been performed to understand the molecular mechanisms of viral infection for predicting drug repurposing candidates. However, such information is spread across many publications and it is very time-consuming to access, integrate, explore, and exploit. We developed CoVex, the first interactive online platform for SARS-CoV-2 and SARS-CoV-1 host interactome exploration and drug (target) identification. CoVex integrates 1) experimentally validated virus-human protein interactions, 2) human protein-protein interactions and 3) drug-target interactions. The web interface allows user-friendly visual exploration of the virus-host interactome and implements systems medicine algorithms for network-based prediction of drugs. Thus, CoVex is an important resource, not only to understand the molecular mechanisms involved in SARS-CoV-2 and SARS-CoV-1 pathogenicity, but also in clinical research for the identification and prioritization of candidate therapeutics. We apply CoVex to investigate recent hypotheses on a systems biology level and to systematically explore the molecular mechanisms driving the virus life cycle. Furthermore, we extract and discuss drug repurposing candidates involved in these mechanisms. CoVex renders COVID-19 drug research systems-medicine-ready by giving the scientific community direct access to network medicine algorithms integrating virus-host-drug interactions. It is available at https://exbio.wzw.tum.de/covex/.

OBJECTIVES: Essential workers in the United States need access to health care services for preventive care and for diagnosis and treatment of illnesses (coronavirus disease 2019 [COVID-19] or other infectious or chronic diseases) to remain healthy and continue working during a pandemic. This study evaluated access to health care services among selected essential workers. METHODS: We used the most recent data from the Behavioral Risk Factor Surveillance System, 2017-2018, to estimate the prevalence of 4 measures of health care access (having health insurance, being able to afford to see a doctor when needed, having a personal health care provider, and having a routine checkup in the past year) by broad and detailed occupation group among 189 208 adults aged 18-64. RESULTS: Of all occupations studied, workers in farming, fishing, and forestry occupations were most likely to have no health insurance (46.4%). Personal care aides were most likely to have been unable to see a doctor when needed because of cost (29.3%). Construction laborers were most likely to lack a personal health care provider (51.1%) and to have not had a routine physical checkup in the past year (50.6%). Compared with workers in general, workers in 3 broad occupation groups-food preparation and serving; building and grounds cleaning and maintenance; and construction trades-had significantly lower levels of health care access for all 4 measures. CONCLUSION: Lack of health insurance and underinsurance were common among subsets of essential workers. Limited access to health care might decrease essential workers' access to medical testing and needed care and hinder their ability to address underlying conditions, thereby increasing their risk of severe outcomes from some infectious diseases, such as COVID-19. Improving access to health care for all workers, including essential workers, is critical to ensure workers' health and workforce stability.

Acute bleeding from portal hypertensive gastropathy (PHG) is an extremely rare event in the natural history of cirrhosis The treatment recommendations include portal pressure reduction strategies including pharmacotherapy with vasoactive agents and beta-blockers and interventional strategies such as transjugular intrahepatic portosystemic shunt placement In this report, we present the case of a patient with cirrhosis in whom acute PHG-related bleed was managed with endoscopic band ligation, a therapeutic modality which has not been described in current literature Our decision to re-purpose a technique for variceal bleeding stems from the fact that during the ongoing COVID-19 pandemic, the technical assistance, resource availability, and sourcing of materials that were required for us to follow recommended management guidelines for acute PHG-related bleed was severely affected due to imposed lockdown between districts and states

Introduction: This study estimated the extent of psychological distress among people losing work during the coronavirus disease of 2019 (COVID-19) pandemic in Australia, and examined associations between distress, nature of work loss and degree of social interaction. Methods: Data were from a baseline online survey of an inception cohort recruited in the weeks following the introduction of physical distancing and movement restrictions to contain the spread of COVID-19 in Australia. These restrictions resulted in widespread unemployment and working hour reduction. Psychological distress was measured using the Kessler-6 scale. Data on nature of work loss, social interactions, demographic, job and occupational characteristics were also collected. Regression modelling was conducted to determine the relationship between work loss, social interactions and psychological distress, accounting for confounders. Results: Among the 551 study participants 31% reported severe psychological distress, 35% in those with job loss and 28% in those still employed but working less. Those who had significantly greater odds of high psychological distress were younger, female, had lost their job and had lower social interactions. The relationship between job loss and distress became non-significant when financial stress, and occupation were included in the regression model, but the protective effect of higher social interactions remained significant. Discussion: There was a high prevalence of psychological distress in people losing work during the COVID-19 pandemic. Age, gender, job loss and social interactions were strongly associated with distress. Interventions that promote social interaction may help to reduce distress during among people losing work during the COVID-19 pandemic.

To describe the importance of critical care clinical research that is not pandemic-focused during pandemic times; outline principles to assist in the prioritization of nonpandemic research during pandemic times; and propose a guiding framework for decisions about whether, when and how to continue nonpandemic research while still honoring the moral and scientific imperative to launch research that is pandemic-focused. DESIGN/DATA SOURCES: Using in-person, email, and videoconference exchanges, we convened an interprofessional clinical research group, conducted a literature review of empirical studies, ethics documents and expert commentaries (2010 to present), and viewed traditional and social media posts (March 2020 to May 2020). Stakeholder consultation involved scientific, ethics, clinical, and administrative leaders. SETTING: Clinical research in the ICU. PATIENTS: Patients with and without coronavirus disease 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: While clinical research should be prioritized to advantage patients with coronavirus disease 2019 in order to care for affected patients, it ideally would not unduly disadvantage patients without coronavirus disease 2019. Thus, timely, rigorous, relevant, and ethical clinical research is needed to improve the care and optimize outcomes for both patients with and without coronavirus disease 2019, acknowledging how many studies that are not exclusively focused on coronavirus disease 2019 remain relevant to patients with coronavirus disease 2019. Considerations to continue nonpandemic-focused research include the status of the pandemic, local jurisdictional guidance, capacity and safety of bedside and research personnel, disposition of patients already enrolled in nonpandemic studies, analyzing characteristics of each nonpandemic-focused study, research oversight, and final reporting requirements. CONCLUSIONS: Deliberation about continuing nonpandemic research should use objective, transparent criteria considering several aspects of the research process such as bedside and research staff safety, infection control, the informed consent model, protocol complexity, data collection, and implementation integrity. Decisions to pause or pursue nonpandemic research should be proportionate, transparent, and revisited as the pandemic abates.

BackgroundMutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may reduce the efficacy of neutralizing monoclonal antibody therapy against coronavirus disease 2019 (COVID-19). We here evaluated the efficacy of casirivimab-imdevimab in patients with mild-to-moderate COVID-19 during the Delta variant surge in Fukushima Prefecture, Japan. MethodsWe enrolled 949 patients with mild-to-moderate COVID-19 who were admitted to hospital between July 24, 2021 and September 30, 2021. Clinical deterioration after admission was compared between casirivimab-imdevimab users (n = 314) and non-users (n = 635). ResultsThe casirivimab-imdevimab users were older (P < 0.0001), had higher body temperature ([] 38{degrees}C) (P < 0.0001) and greater rates of history of cigarette smoking (P = 0.0068), hypertension (P = 0.0004), obesity (P < 0.0001), and dyslipidemia (P < 0.0001) than the non-users. Multivariate logistic regression analysis demonstrated that receiving casirivimab-imdevimab was an independent factor for preventing deterioration (odds ratio 0.448; 95% confidence interval 0.263-0.763; P = 0.0023). Furthermore, in 222 patients who were selected from each group after matching on the propensity score, deterioration was significantly lower among those receiving casirivimab-imdevimab compared to those not receiving casirivimab-imdevimab (7.66% vs 14.0%; p = 0.021). ConclusionThis real-world study demonstrates that casirivimab-imdevimab contributes to the prevention of deterioration in COVID-19 patients after hospitalization during a Delta variant surge. SummaryThis real-world retrospective study demonstrates the contribution of treatment with casirivimab-imdevimab to the prevention of deterioration in patients with mild-to-moderate coronavirus disease 2019 (COVID-19) even during the Delta variant pandemic.

Right lobe living donor liver transplantation (LDLT) is a major development in adult LDLT that has significantly increased the donor pool by providing larger graft size and by decreasing risk of small-for-size graft syndrome. However, right lobe anatomy is complex, not only from the inflow but also from the outflow perspective. Outflow reconstruction is one of the key requirements of a successful LDLT and venous drainage of the liver graft is just as important as hepatic inflow for the integrity of graft function. Outflow complications may cause acute graft failure which is not always easy to diagnose. The right lobe graft consists of two sections and three hepatic venous routes for drainage that require reconstruction. In order to obtain a congestion free graft, several types of vascular conduits and postoperative interventions are needed to assure an adequate venous allograft drainage. This review described the anatomy, functional basis and the evolution of outflow reconstruction in right lobe LDLT.

The novel coronavirus 2019 (COVID-19) pandemic has placed an unprecedented strain on healthcare systems and frontline workers worldwide. The large influx of these high acuity patients has placed pressure on services to modify their operations to meet this increased need. We describe how the Vascular Access Service (VAS) at a New York City academic hospital adopted a team-based approach to efficiently meet increased demand for vascular access devices, while ensuring safety and conserving personal protective equipment.

The aim of this research is to examine the new landscape that is taking shape in the tourism economy, due to the adoption of technological innovations. The technologies and systems used to make the most of the resulting interdisciplinary and multilingual big data, the methods by which heterogeneous elements from different sources are incorporated to bring new knowledge, and the modern services that are ultimately implemented and provided to the public, as well as the people involved in this process, and those who benefit from the new services are among the issues analyzed. The work is not limited to a simple mapping of space but concludes with an evaluation of the systems already implemented and the various methods of analysis and exploitation of large-scale data for this industry, which is based on detailed research of the current literature to identify the potential gaps for future research. This is a literature review. The authors have identified the content of this research on well-known online databases which include scholar, google and Scopus. They used the appropriate keywords such as big data & tourism innovation to reach the publications used in this research, also given attention on using recent papers which are derived from reliable journals. The research has concluded that the use of big data in the tourism sector is a rising trend. Big data creates expectations for a better understanding of tourism demand and the adjustment of supply by tourism companies to meet the demands of tourists and the profitable activity of tourism businesses. There is a need to examine how can big data help the hotels to deal with Covid-19 pandemic, which can be a topic for future research. Big data is one of the most recent trends on innovation, Information Communication Technologies (ICT) and knowledge management. Hence, there is a need to gather and analyze the existing publications which concern the tourist industry. The originality of this research stems from making an analysis of the current situation as well as it is a bridge to the future by making suggestions on how future research can be shaped. The key limitation of this research resides on that it focuses on the existing literature and used secondary data. However, it gives directions for the future research which can take place with primary data collection. ? 2021 Belias et al.

Receptor tyrosine kinases (RTKs) are single-pass membrane proteins that regulate cell growth, differentiation, motility, and metabolism. Here, we review recent advancements in RTK structure determination and in the understanding of RTK activation. We argue that further progress in the field will necessitate new ways of thinking, and we introduce the concept that RTK dimers explore ensembles of microstates, each characterized by different kinase domain dimer conformations, but the same extracellular domain dimer structure. Many microstates are phosphorylation-competent and ensure the phosphorylation of one specific tyrosine. The prevalence of each microstate correlates with its stability. A switch in ligand will lead to a switch in the extracellular domain configuration and to a subsequent switch in the ensemble of microstates. This model can explain how different ligands produce specific phosphorylation patterns, how receptor overexpression leads to enhanced signaling even in the absence of activating ligands, and why RTK kinase domain structures have remained unresolved in cryogenic electron microscopy studies.

PurposeThe study aims to examine factors that influence customers' intention to use online food delivery applications using a smartphone. The factors examined in this study are based on the existing theory of Unified Theory of Acceptance and Use of Technology (UTAUT) namely performance expectancy, effort expectancy, social influence, information quality, price-saving orientation and time-saving orientation towards intention to use the applications. Moreover, this research model also has been expanded with an additional dimension, attitude towards online food delivery services which lead to the intention to use online food delivery services through a smartphone. Furthermore, the present study also tested the role of age as moderator constructs between attitude towards online food delivery services and intention to use online food delivery services through a smartphone.Design/methodology/approachThe study employed a quantitative method and 256 respondents participated in this study. The questionnaires are distributed using a convenience sampling technique and the data is analysed using partial least square approach.FindingsThe result shows that four (4) constructs, i.e. social influence, information quality, price-saving orientation and time-saving orientation have a positive relationship and significant effect on attitude towards online food delivery service where it enhances the intention to use the application. Attitude towards online food delivery services also has a significant effect on the intention to use. Furthermore, age was not found significant to moderate the relationship between attitude and intention to use.Practical implicationsThe output of this study has several practical contributions such as enhances the existing knowledge and skillset of the shared-economy industry, online food delivery service providers as well as restaurant owners in improving the quality of life of the customers. It also provides contextual knowledge and a deeper understanding of online food delivery applications for customers in Malaysia.Originality/valueThe findings provide a guiding principle for improving the present determinant factors, attitude towards online food delivery service and intention to use online food delivery applications.

Currently, the COVID-19 pneumonia epidemic is spreading worldwide. Pulmonary imaging plays an important role. The pulmonary imaging (chest computed tomography and Digital radiography) are indispensable for definitive diagnosis and reexamination. It should be noted that nosocomial infection is not uncommon. Many cases including health workers are infected. This is the experience of our radiology department's protocols during the outbreak, we used this protocol to cope with the COVID-19 in Sichuan Province besidesthere is zero infection for health workers during the whole epidemic. So, we would like to share our experience to other radiologists to avoid the nosocomial infection as low as possible. We have six key points for updating the protocol in the epidemic period of COVID-19: 1. Triage system: three-level triage, 2. Maximum Protection Principle, 3. Technical operation principle: careful, fast and stable, 4. Radiologist's Responsibility and Notice, 5. Disinfection measures of machine room, 6. Hospital information construction, network office, accelerate the sharing of imaging, and carry out MDT consultation.

OBJECTIVES: We describe newly established guidance for guideline developers at the World Health Organization (WHO) on the process and procedures for developing a rapid advice guideline in the context of a public health emergency (e.g., the 2014 Ebola epidemic). STUDY DESIGN AND SETTING: We based our approach on established rapid review methods, which were incorporated into existing WHO guideline development processes. Guidance was further informed by in-depth discussions of issues related to rapid guideline development with WHO staff (n = 6), who oversee the Organization's response to emergencies. RESULTS: We discuss criteria for considering if a rapid advice guideline is appropriate and feasible and outline the roles of various contributors across the phases of development. Further, we describe the methods and steps involved in performing rapid reviews, which are more fluid and iterative than for a standard guideline process. In general, rapid advice guidelines involve a shorter timeline, narrower scope, and the use of abbreviated methods for the evidence review. CONCLUSION: Important differences exist between developing a standard guideline and a rapid advice guideline. However, the core principles for WHO guidelines apply to rapid advice guidelines including minimizing bias, applying transparent processes and the use of explicit methods.

BACKGROUND Hundreds of variants associated with atopic dermatitis (AD) and psoriasis, two common inflammatory skin disorders, have previously been discovered through genome-wide association studies (GWAS). The majority of these variants are in non-coding regions and their target genes remain largely unclear. OBJECTIVE We sought to understand the effects of these non-coding variants on the development of AD and psoriasis by linking them to the genes they regulate. METHODS We constructed genomic 3D maps of human keratinocytes during differentiation using capture Hi-C targeting more >20, 000 promoters and 214 GWAS variants and combined this with transcriptome and epigenomic datasets. We validated our results with reporter assays, CRISPR activation and examination of patient gene expression from previous studies. RESULTS We identified 118 target genes of 82 AD and psoriasis GWAS-variants. Differential expression of 49% (58) of the 118 target genes occurred in either AD or psoriatic lesions, many of which were not previously linked to any skin disease. We highlight AFG1L, CLINT1, ADO, LINC00302, and RP1-140J1.1 genes and provide further evidence for their potential roles in AD and psoriasis. CONCLUSIONS Our work focuses on skin barrier pathology through investigation of the interaction profile of GWAS-variants during keratinocyte differentiation. We provide a catalogue of candidate genes that could modulate the risk of AD and psoriasis. Given that only 35% of the target genes are the nearest gene to the known GWAS variants, we expect that our work will contribute to the discovery of novel pathways involved in AD and psoriasis.

BACKGROUND: Systemic rheumatic diseases are characterized by diverse symptoms that are exacerbated by stressors. QUESTIONS/PURPOSES: Our goal was to identify COVID-19-related stressors that patients associated with worsening rheumatic disease symptoms. METHODS: With approval of their rheumatologists, patients at an academic medical center were interviewed with open-ended questions about the impact of COVID-19 on daily life. Responses were analyzed with qualitative methods using grounded theory and a comparative analytic approach to generate categories of stressors. RESULTS: Of 112 patients enrolled (mean age 50 years, 86% women, 34% non-white or Latino, 30% with lupus, 26% with rheumatoid arthritis), 2 patients had SARS-CoV-2 infection. Patients reported that coping with challenges due to the pandemic both directly and indirectly worsened their rheumatic disease symptoms. Categories associated with direct effects were increased fatigue (i.e., from multitasking, physical work, and taking precautions to avoid infection) and worsening musculoskeletal and cognitive function. Categories associated with indirect effects were psychological worry (i.e., about contracting SARS-COV-2, altering medications, impact on family, and impact on job and finances) and psychological stress (i.e., at work, at home, from non-routine family responsibilities, about uncertainty related to SARS-CoV-2, and from the media). Patients often reported several effects coalesced in causing more rheumatic disease symptoms. CONCLUSION: Coping with the COVID-19 pandemic was associated with rheumatic diseaseCrelated physical and psychological effects, even among patients not infected with SARS-CoV-2. According to patients, these effects adversely impacted their rheumatic diseases. Clinicians will need to ascertain the long-term sequelae of these effects and determine what therapeutic and psychological interventions are indicated. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11420-020-09798-w) contains supplementary material, which is available to authorized users.