Assembly reactions of SARS-CoV-2 nucleocapsid protein with nucleic acid (preprint)

The viral genome of SARS-CoV-2 is packaged by the nucleocapsid (N-) protein into ribonucleoprotein particles (RNPs), 38{+/-}10 of which are contained in each virion. Their architecture has remained unclear due to the pleomorphism of RNPs, the high flexibility of N-protein intrinsically disordered regions, and highly multivalent interactions between viral RNA and N-protein binding sites in both N-terminal (NTD) and C-terminal domain (CTD). Here we explore critical interaction motifs of RNPs by applying a combination of biophysical techniques to mutant proteins binding different nucleic acids in an in vitro assay for RNP formation, and by examining mutant proteins in a viral assembly assay. We find that nucleic acid-bound N-protein dimers oligomerize via a recently described protein-protein interface presented by a transient helix in its long disordered linker region between NTD and CTD. The resulting hexameric complexes are stabilized by multi-valent protein-nucleic acid interactions that establish crosslinks between dimeric subunits. Assemblies are stabilized by the dimeric CTD of N-protein offering more than one binding site for stem-loop RNA. Our study suggests a model for RNP assembly where N- protein scaffolding at high density on viral RNA is followed by cooperative multimerization through protein-protein interactions in the disordered linker.

Assembly of SARS-CoV-2 ribonucleosomes by truncated N* variant of the nucleocapsid protein (preprint)

The Nucleocapsid (N) protein of SARS-CoV-2 compacts the RNA genome into viral ribonucleoprotein (vRNP) complexes within virions. Assembly of vRNPs is inhibited by phosphorylation of the N protein SR region. Several SARS-CoV-2 variants of concern carry N protein mutations that reduce phosphorylation and enhance the efficiency of viral packaging. Variants of the dominant B.1.1 viral lineage also encode a truncated N protein, termed N* or {Delta}(1-209), that mediates genome packaging despite lacking the N-terminal RNA-binding domain and SR region. Here, we show that {Delta}(1-209) and viral RNA assemble into vRNPs that are remarkably similar in size and shape to those formed with full-length N protein. We show that assembly of {Delta}(1-209) vRNPs requires the leucine-rich helix (LH) of the central disordered region, and that the LH promotes N protein oligomerization. We also find that fusion of a phosphomimetic SR region to {Delta}(1-209) inhibits RNA binding and vRNP assembly. Our results provide new insights into the mechanisms by which RNA binding promotes N protein self-association and vRNP assembly, and how this process is modulated by SR phosphorylation.

Stigma and posttraumatic growth among COVID-19 survivors during the first wave of the COVID-19 pandemic in Malaysia: a multicenter cross-sectional study.

Background: Contracting COVID-19 can cause negative and distressing psychological sequelae, but traumatic stressors may also facilitate the development of positive psychological change beyond an individual's previous level of adaptation, known as posttraumatic growth (PTG). As a result, studies have investigated the negative effects of COVID-19 on mental health, but data on PTG among patients who have recovered from COVID-19 remains limited. This study aims to evaluate the level of PTG and its associations with stigma, psychological complications, and sociodemographic factors among COVID-19 patients 6 months post-hospitalization. Method: A cross-sectional online survey of 152 COVID-19 patients was conducted after 6 months of being discharged from Hospital Canselor Tuanku Muhriz, MAEPS Quarantine Center, or Hospital Sungai Buloh, Malaysia. Patients completed a set of questionnaires on sociodemographic and clinical data. The Posttraumatic Growth Inventory (PTGI-SF) was used to assess the level of PTG, the Kessler Psychological Distress (K6) was used to measure the degree of psychological distress, the General Anxiety Disorder-7 (GAD-7) was used to evaluate the severity of anxiety symptoms, the Patient Health Questionnaire (PHQ-9) was used to assess the severity of depression symptoms, and the Explanatory Model Interview Catalog Stigma Scale (EMIC-SS) was used to record the degree of perceived stigma toward COVID-19. Results: The median PTGI SF score of the respondents was 40.0 (Interquartile range 16.0). Multivariable general linear model with bootstrapping (2,000 replications) revealed factors that significantly predicted PTG, which were at the higher level of the perceived stigma score, at 37 (B = 0.367, 95% CI = 0.041 to 0.691, p = 0.026), among the Malay ethnicity (B = 12.767, 95% CI 38 = 7.541 to 17.993, p < 0.001), retirees (B = -12.060, 95% CI = -21.310 to -2.811, p = 0.011), and those with a history of medical illness (B = 4.971, 95% CI = 0.096 to 9.845, p = 0.046). Conclusion: Experiencing stigma contributed to patients' PTG in addition to psychosocial factors such as ethnicity, history of medical illness, and retirement.

COVID-19 and Airline Performance in the Asia Pacific region

Health risks associated with coronavirus disease 2019 (COVID-19) have severely affected the financial stability of airline companies globally. Recapturing financial stability following this crisis depends heavily on these companies' ability to attain efficient and productive operations. This study uses several empirical approaches to examine key factors contributing to carriers sustaining high productivity prior to, during and after a major recession. Findings suggest, regardless of economic conditions, that social distancing which requires airline companies in the Asia Pacific region to fly with a significant percentage of unfilled seats weakens the performance of those companies. Furthermore, efficient operations do not guarantee the avoidance of productivity declines, especially during a recession.

Stigma, Sociodemographic Factors, and Clinical Factors Associated with Psychological Distress among COVID-19 Survivors during the Convalescence Period: A Multi-Centre Study in Malaysia

High rates of psychological distress among COVID-19 survivors and stigmatisation have been reported in both early and late convalescence. This study aimed to compare the severity of psychological distress and to determine the associations among sociodemographic and clinical characteristics, stigma, and psychological distress among COVID-19 survivors across two different cohorts at two different time points. Data were collected cross-sectionally in two groups at one month and six months post-hospitalisation among COVID-19 patient from three hospitals in Malaysia. This study assessed psychological distress and the level of stigma using the Kessler Screening Scale for Psychological Distress (K6) and the Explanatory Model Interview Catalogue (EMIC) stigma scale, respectively. At one month after discharge, significantly lower psychological distress was found among retirees (B = −2.207, 95% confidence interval [95% CI] = −4.139 to −0.068, p = 0.034), those who received up to primary education (B = −2.474, 95% CI = −4.500 to −0.521, p = 0.014), and those who had an income of more than RM 10,000 per month (B = −1.576, 95% CI = −2.714 to −0.505, p = 0.006). Moreover, those with a history of psychiatric illness [one month: (B = 6.363, 95% CI = 2.599 to 9.676, p = 0.002), six months: (B = 2.887, CI = 0.469–6.437, p = 0.038)] and sought counselling services [one month: (B = 1.737, 95% CI = 0.385 to 3.117, p = 0.016), six months: (B = 1.480, CI = 0.173–2.618, p = 0.032)] had a significantly higher severity of psychological distress at one month and six months after discharge from the hospital. The perceived stigma of being infected with COVID-19 contributed to greater severity of psychological distress. (B = 0.197, CI = 0.089–0.300, p = 0.002). Different factors may affect psychological distress at different periods of convalescence after a COVID-19 infection. A persistent stigma contributed to psychological distress later in the convalescence period.

When fear about health hurts performance: COVID-19 and its impact on employee's work

This study utilized terror management and conservation of resources theory to fulfill its aim of investigating the effects of fear of contamination of COVID-19 on performance of employees in the banking sector of Pakistan. A survey was conducted to collect data in two waves from 206 bank employees in Punjab region. SPSS was used for data analysis. The results demonstrated that such fear leads to emotional exhaustion which in turn negatively affects employee's work performance. However, the perceptions of better precautionary measures taken by the organization against the spread of the disease moderated the said relationship and weakened the strength of fear on performance through emotional exhaustion. Amid the widespread fear, panic and detrimental effects of COVID-19 on organizations and economies of the worlds, this research has implications for policy makers by showing the importance of organizational measures taken and displayed to employees in decreasing the negative effects of extensive fear and uncertainty prevailing due to the pandemic.

The moderating role of industry clockspeed on the relation between supply chain integration practices and new product flexibility.

This study assessed the firm's new product flexibility in the recovery phase of COVID-19. Using the theoretical lens of organizational information processing theory, it established the relationship between supply chain integration practices (supply chain planning, internal integration, and supplier involvement) and new product flexibility. It also explained the moderating effect of industry clockspeed on supply chain integration practices and new product flexibility with the help of contingency theory. This study used an online survey method to collect data from plant managers, and we received 256 useable responses. We conducted a confirmatory factor analysis to test the validity and reliability of the scales, and we tested hypotheses using moderated multiple regression technique. The results showed significant positive relationships between supply chain integration practices and new product flexibility. The moderating effects hypotheses showed that industry clockspeed significantly and positively moderated on supply chain planning-new product flexibility and internal integration-new product flexibility links. But it negatively moderated on supplier involvement and new product flexibility. Our study departs from earlier studies in the field that were conducted under normal circumstances. We conducted our study in the recovery phase of COVID-19 in Pakistan, when firms, after fourteen days of complete lockdown, resumed their operations and experienced a new business landscape.

Post-COVID-19 health-care utilization: one year after the 2020 first wave in Brunei Darussalam.

Objective: Patients who recover from coronavirus disease (COVID-19) infection are at risk of long-term health disorders and may require prolonged health care. This retrospective observational study assesses the number of health-care visits before and after COVID-19 infection in Brunei Darussalam. Methods: COVID-19 cases from the first wave with 12 months of follow-up were included. Health-care utilization was defined as health-care visits for consultations or investigations. Post-COVID condition was defined using the World Health Organization definition. Results: There were 132 cases; 59.1% were male and the mean age was 37.1 years. The mean number of health-care visits 12 months after recovery from COVID-19 (123 cases, 93.2%; mean 5.0 ± 5.2) was significantly higher than the prior 12 months (87 cases, 65.9%, P < 0.001; mean 3.2 ± 5.7, P < 0.001). There was no significant difference when scheduled COVID-19 visits were excluded (3.6 ± 4.9, P = 0.149). All 22 cases with moderate to critical disease recovered without additional health-care visits apart from planned post-COVID-19 visits. Six patients had symptoms of post-COVID condition, but none met the criteria for diagnosis or had alternative diagnoses. Discussion: There were significantly more health-care visits following recovery from COVID-19. However, this was due to scheduled post-COVID-19 visits as per the national management protocol. This protocol was amended before the second wave to omit post-COVID-19 follow-up, except for complicated cases or cases with no documented radiological resolution of COVID-19 pneumonia. This will reduce unnecessary health-care visits and conserve precious resources that were stretched to the limit during the pandemic.

Stigma, Sociodemographic Factors, and Clinical Factors Associated with Psychological Distress among COVID-19 Survivors during the Convalescence Period: A Multi-Centre Study in Malaysia.

High rates of psychological distress among COVID-19 survivors and stigmatisation have been reported in both early and late convalescence. This study aimed to compare the severity of psychological distress and to determine the associations among sociodemographic and clinical characteristics, stigma, and psychological distress among COVID-19 survivors across two different cohorts at two different time points. Data were collected cross-sectionally in two groups at one month and six months post-hospitalisation among COVID-19 patient from three hospitals in Malaysia. This study assessed psychological distress and the level of stigma using the Kessler Screening Scale for Psychological Distress (K6) and the Explanatory Model Interview Catalogue (EMIC) stigma scale, respectively. At one month after discharge, significantly lower psychological distress was found among retirees (B = -2.207, 95% confidence interval [95% CI] = -4.139 to -0.068, p = 0.034), those who received up to primary education (B = -2.474, 95% CI = -4.500 to -0.521, p = 0.014), and those who had an income of more than RM 10,000 per month (B = -1.576, 95% CI = -2.714 to -0.505, p = 0.006). Moreover, those with a history of psychiatric illness [one month: (B = 6.363, 95% CI = 2.599 to 9.676, p = 0.002), six months: (B = 2.887, CI = 0.469-6.437, p = 0.038)] and sought counselling services [one month: (B = 1.737, 95% CI = 0.385 to 3.117, p = 0.016), six months: (B = 1.480, CI = 0.173-2.618, p = 0.032)] had a significantly higher severity of psychological distress at one month and six months after discharge from the hospital. The perceived stigma of being infected with COVID-19 contributed to greater severity of psychological distress. (B = 0.197, CI = 0.089-0.300, p = 0.002). Different factors may affect psychological distress at different periods of convalescence after a COVID-19 infection. A persistent stigma contributed to psychological distress later in the convalescence period.

Nearpod Use as a Learning Platform to Improve Student Learning Motivation in an Elementary School

Education sector is heavily affected by COVID-19 pandemic, leading to reduced learning motivation among students. Factors including dismal learning environment, stress, and anxiety are believed to be the reasons of students' lower motivation among students. This study investigated the use of Nearpod in an elementary school to improve student learning motivation during online learning. In this qualitative experimental research with thematic analysis, three classes with a total of 51 students and three teachers were participating for one week. The results of the study showed that gamification and interactivity of Nearpod help build up and develop students' learning interests, leading to greater attention, engagement, and improvement of student attendance rates. Some suggestions on how to effectively integrate gamification in learning are postulated.

GRADUATE UNEMPLOYMENT DURING THE COVID-19 PANDEMIC IN MALAYSIA

The COVID-19 epidemic has had a negative impact on many sectors, particularly the Malaysian economy. To prevent the spread of this illness, the government has taken extraordinary steps, issuing Movement Control Orders (MCO) throughout the nation. The consequence of this MCO prevents the firm from working regularly and creates losses to the point where the company must lay off some of its workers to fund the company's operating expenses. This has resulted in a rise in unemployment, as well as making it harder for graduates to join the labour market today. As a result, a research was done to identify the reasons that made it difficult for potential graduates to access the labour market during the COVID-19 epidemic, as well as solutions to this issue. Due to the Movement Control Order, a total of 200 respondents completed a questionnaire created using the Google Form platform and disseminated online (MCO). According to the conclusions of this research, the primary element that makes it difficult for graduates is due to factors of the economic slowdown, particularly during current pandemic, which generates heightened rivalry between graduates and retrenched workers to access the labour market. The study's findings are likely to make prospective graduates more aware of the problems that await them after graduation.

Melamine-derived N-rich C-entrapped Au nanoparticles for sensitive and selective monitoring of dopamine in blood samples† † Electronic supplementary information (ESI) available. See https://doi.org/10.1039/d2ra02754b

Several neurological disorders, including Parkinson's disease, schizophrenia, human immunodeficiency virus infection, and restless leg syndrome, majorly result from disruption in the dopamine (DA) level. Thus, useful information about the treatment and prevention of various genetic majorly mental health problems can be obtained through precise and real-time monitoring of DA. Herein, we report the fabrication of novel N-rich carbon-coated Au nanoparticles (NC@Au-NPs) by deriving from melamine-crosslinked citrate-stabilized Au NPs. NC@Au-NPs offer fast electro-oxidation efficacy towards DA, because of strong electrostatic attraction between negatively charged NC@Au-NPs and positively charged DA. The catalytic efficacy and shelf life of the designed system were further boosted by applying a mixture of polydopamine (PDA) and benzimidazolium-1-acetate ionic liquid (IL) as a sandwich between the working electrode surface (graphitic pencil electrode: GPE) and the designed nanohybrid NC@Au-NPs as a redox mediator. The results indicate that the designed novel NC@Au/PDA–IL/GPE exhibits excellent sensitivity, selectivity, and reproducibility over a wide linear range (50–1000 nm) and a low detection limit of 0.002 μM ± 0.001 as well. The developed sensor was successfully applied to monitor DA in the blood of COVID-19 quarantined patients and pharmaceutical samples with high accuracy, thus suggesting a powerful tool for the diagnosis of mental problems. Several neurological disorders, including Parkinson's disease, schizophrenia, human immunodeficiency virus infection, and restless leg syndrome, majorly result from disruption in the dopamine (DA) level.

Melamine-derived N-rich C-entrapped Au nanoparticles for sensitive and selective monitoring of dopamine in blood samples.

Several neurological disorders, including Parkinson's disease, schizophrenia, human immunodeficiency virus infection, and restless leg syndrome, majorly result from disruption in the dopamine (DA) level. Thus, useful information about the treatment and prevention of various genetic majorly mental health problems can be obtained through precise and real-time monitoring of DA. Herein, we report the fabrication of novel N-rich carbon-coated Au nanoparticles (NC@Au-NPs) by deriving from melamine-crosslinked citrate-stabilized Au NPs. NC@Au-NPs offer fast electro-oxidation efficacy towards DA, because of strong electrostatic attraction between negatively charged NC@Au-NPs and positively charged DA. The catalytic efficacy and shelf life of the designed system were further boosted by applying a mixture of polydopamine (PDA) and benzimidazolium-1-acetate ionic liquid (IL) as a sandwich between the working electrode surface (graphitic pencil electrode: GPE) and the designed nanohybrid NC@Au-NPs as a redox mediator. The results indicate that the designed novel NC@Au/PDA-IL/GPE exhibits excellent sensitivity, selectivity, and reproducibility over a wide linear range (50-1000 nm) and a low detection limit of 0.002 µM ± 0.001 as well. The developed sensor was successfully applied to monitor DA in the blood of COVID-19 quarantined patients and pharmaceutical samples with high accuracy, thus suggesting a powerful tool for the diagnosis of mental problems.

Clinical and demographic characteristics of COVID-19 cases in Brunei Darussalam: comparison between the first and second waves, 2020 and 2021.

Objective: Differences in clinical manifestations between strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported. This retrospective descriptive study compares the clinical and demographic characteristics of all confirmed coronavirus disease (COVID-19) cases admitted to the National Isolation Centre (NIC) in the first wave and at the beginning of the second wave of the pandemic in Brunei Darussalam. Methods: All COVID-19 cases admitted to the NIC between 9 March and 6 May 2020 (first wave) and 7-17 August 2021 (second wave) were included. Data were obtained from NIC databases and case characteristics compared using Student's t-tests and χ2 tests, as appropriate. Results: Cases from the first wave were significantly older than those from the second wave (mean 37.2 vs 29.7 years, P < 0.001), and a higher proportion reported comorbidities (30.5% vs 20.3%, P = 0.019). Cases from the second wave were more likely to be symptomatic at admission (77.7% vs 63.1%, P < 0.001), with a higher proportion reporting cough, anosmia, sore throat and ageusia/dysgeusia; however, myalgia and nausea/vomiting were more common among symptomatic first wave cases (all P < 0.05). There was no difference in the mean number of reported symptoms (2.6 vs 2.4, P = 0.890). Discussion: Our study showed clear differences in the profile of COVID-19 cases in Brunei Darussalam between the first and second waves, reflecting a shift in the predominating SARS-CoV-2 strain. Awareness of changes in COVID-19 disease manifestation can help guide adjustments to management policies such as duration of isolation, testing strategies, and criteria for admission and treatment.

Service innovation in small neighborhood family firms: An advanced approach to enhance employee's performance through social and psychological rewards.

This research study focuses on the employee's job performance of private small firms during the post COVID-19 situation. After the COVID these small family firms try to regain their business, but their efforts are not that much successful. This situation creates a financial crisis in these firms, and they are unable to provide sufficient monetary rewards to their employees. This situation creates unrest among the employees of these small firms. To manage this issue, social rewards and psychological rewards played their role. The study uses a causal research design with a correlational study design in a non-contrived environment. Minimal researcher interference has been assured. AMOS 24 has dealt with the mediation in study design with bootstrap methodology. The study was conducted on 250 employees of different private small family firms across Punjab province using a proportionate stratified sampling technique. A study's finding suggests that top management enhances employee performance in their organizations by introducing the organization's psychological rewards. In contrast, introducing social rewards does not significantly impact employee performance while considering satisfaction and motivation as a mediating variable.

Challenges during the second wave of COVID-19 in Brunei Darussalam: National Isolation Centre to National COVID-19 Hospital.

Problem: Soon after the start of the second wave of coronavirus disease 2019 (COVID-19) in Brunei Darussalam, which was confirmed to be due to the more infectious Delta strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it became apparent that the National Isolation Centre (NIC) was not coping. Context: The NIC was the only isolation and treatment centre for COVID-19 in Brunei Darussalam. During the first wave and the first 11 days of the second wave, all confirmed cases were admitted to the NIC for isolation and treatment in line with the management strategy to isolate all confirmed cases to control the outbreak. Action: The Ministry of Health opened five community isolation centres and two quarantine centres to divert asymptomatic and mild cases from the NIC. The community isolation centres also functioned as triage centres for the NIC, and the quarantine centres accommodated recovered patients who did not have their own quarantine facilities. Outcome: The community isolation and quarantine centres diverted cases from the NIC and enabled recovered cases to be transferred to these step-down facilities. This reduced the NIC's occupancy to a safe level and enabled the reorganization of the NIC to function as a treatment centre and a national COVID-19 hospital. Discussion: During any disease outbreak, health facilities must be prepared to adapt to changing situations. Strong leadership, stakeholder commitments, teamwork and constant communication are important in this process.

Postal Item Delivery Route Optimization Based On Close-Open Mix Vehicle Routing Problem

Postal delivery is the world's longest-running service business process. Every city on the planet has this service, which is supported by a network of various depots serving as collection and delivery points. In distributing postal item delivery, Pos Indonesia through the Postal Processing Centre (PPC) is a distribution streamline that connects cities and regions with delivery centres closer to the final customer. Pos Indonesia has previously established a distribution pattern based on a zone-based system comprising a primary distribution centre and various delivery centres, delivery schedules, internal fleets, and predetermined routes.However, with reduced production capacity, as demonstrated by reducing traditional mail and less than truckload operations and anticipating customer needs for timely delivery, delivery patterns with fixed schedules and the internal fleet are unable to address this issue. Close-Open Mixed Vehicle Routing Problem (COMVRP) is proposed to optimize delivery by involving external fleets, and this is to reduce transportation costs where external fleets do not have fixed costs and do not need to return to PPC after delivery. The Genetic Algorithm is used to find heuristic solutions for each delivery history after Nearest Neighbor (NN)implementationto validate vehicle routes. Combined COMVRP-NN-GA produces a set of solutions, which will be used in the Monte Carlo Simulation (MCS). The results demonstrate that COMVRP outperforms existing scenarios, from optimizing six-vehicle routes to estimating five routes using a single external vehicle route, significantly reducing total mileage. The simulation findings based on the historical delivery dataset may be used to develop future delivery patterns based on the number of vehicles and total route distance and reduce transportation costs.

The effects of the COVID-19 pandemic on healthcare workers' psychological and mental health: The moderating role of felt obligation.

BACKGROUND: The ravages of COVID-19 have created a worldwide emergency in healthcare units. Under these circumstances, the perception of an infection threat is primarily affecting the employees' performance in reducing contagion effects. OBJECTIVE: The purpose of this study is to develop substantial measures of support for healthcare employees to maintain adequacy in job performance. METHODS: Data were collected from state-owned hospitals in Pakistan to test the current study's proposed model. We applied structural equation modeling through a partial least square regression in addition to the blindfolding approach in Smart-PLS. Confirmatory factor analysis was also employed to measure the study's validity. RESULTS: The current study's findings show that the perception of a threat from COVID-19 and the inadequate protective measures have influenced frontline healthcare workers' performance levels. The mediating path of depression symptoms indicated the threat of COVID-19 and the absence of protective measures as potential determinants of poor performance. However, an employee's ability to feel obligated toward their job duties reduces the effect of depression on employee performance. CONCLUSION: The current model highlights an individual's feelings of obligation to maintain their performance level by minimizing the effect of depression and professional anxiety. The present study extensively described the psychological constraints healthcare workers are facing during the current pandemic. Current research addressing healthcare employees' mental health is vital for better prevention and control during pandemic circumstances. The current study's findings extend the emerging understanding of employee psychology in such circumstances.

COVID-19 patients with negative results on initial screening: Experience of Brunei Darussalam.

In any infectious disease outbreak, early diagnosis, isolation of cases and quarantine of contacts are central to disease containment. In Brunei Darussalam, suspected cases of coronavirus disease 2019 (COVID-19) were quarantined either at home or at designated centres and were tested immediately for severe acute respiratory syndrome coronavirus 2. We report on 10 cases of COVID-19 that initially tested negative for COVID-19 and were positive on re-testing after becoming symptomatic. These cases comprised 3.8% of the 266 total confirmed COVID-19 cases in Brunei Darussalam as of 9 July 2021, when this study was conducted. All the cases were in quarantine at home and were tested early during their quarantine period. Since then, home quarantine has been replaced by quarantine at designated centres only, with testing on the 12th day of quarantine.