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Owing to the continuous variant of the COVID-19 virus, the present epidemic may persist for a long time, and each breakout displays strongly region/time-dependent characteristics. Predicting each specific burst is the basic task for the corresponding strategies. However, the refinement of prevention and control measures usually means the limitation of the existing records of the evolution of the spread, which leads to a special difficulty in making predictions. Taking into account the interdependence of people' s travel behaviors and the epidemic spreading, we propose a modified logistic model to mimic the COVID-19 epidemic spreading, in order to predict the evolutionary behaviors for a specific bursting in a megacity with limited epidemic related records. It continuously reproduced the COVID-19 infected records in Shanghai, China in the period from March 1 to June 28, 2022. From December 7, 2022 when Mainland China adopted new detailed prevention and control measures, the COVID-19 epidemic broke out nationwide, and the infected people themselves took "ibuprofen” widely to relieve the symptoms of fever. A reasonable assumption is that the total number of searches for the word "ibuprofen” is a good representation of the number of infected people. By using the number of searching for the word "ibuprofen” provided on Baidu, a famous searching platform in Mainland China, we estimate the parameters in the modified logistic model and predict subsequently the epidemic spreading behavior in Shanghai, China starting from December 1, 2022. This situation lasted for 72 days. The number of the infected people increased exponentially in the period from the beginning to the 24th day, reached a summit on the 31st day, and decreased exponentially in the period from the 38th day to the end. Within the two weeks centered at the summit, the increasing and decreasing speeds are both significantly small, but the increased number of infected people each day was significantly large. The characteristic for this prediction matches very well with that for the number of metro passengers in Shanghai. It is suggested that the relevant departments should establish a monitoring system composed of some communities, hospitals, etc. according to the sampling principle in statistics to provide reliable prediction records for researchers. © 2023 Chinese Physical Society.
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Purpose: to analyze the ability of the National Health Insurance mobile service quality to build BPJS brand image and public trust to increase intention to use online services during the Covid period. The background of this research is based on the phenomenon in the form of complaints on the quality of online services and research gaps on the effect of service quality on the intention to use online services. Brand image and trust are offered as a mediation for gaps in previous research results. Design/ methodology/approach: The type of research is quantitative, using a pre-existing measurement scale related to mobile service quality, brand image, trust and intention. Involving a sample of 140 BPJS users during the Covid pandemic. It is difficult to identify the population size, the sample size is determined by the formulation of a constant value of 5 multiplied by 28 indicators. The technique of selecting respondents was carried out by means of non-probability random sampling. PLS SEM model as an analysis tool. Findings: The results of this study indicate that the direct relationship of mobile service quality on brand image, trust and intention shows significant positive results. Furthermore, the influence of brand image on trust shows significant results. The influence of brand image and trust on intention is also found to be significantly positive. Practical/implications: although management policies encourage customers to use mobile services more, the public still considers the trustworthy image of BPJS to develop their intention to use mobile application services. The government must remain consistent in ensuring that the quality of mobile service is not compromised because the implications for BPJS image and public trust are at stake. Through the person in charge at BPJS, the government must continue to consistently evaluate and improve the system and educate the public regarding this BPJS health mobile service system. Originality/value: This research offers new insights, filling gaps in studies on national health insurance mobile services during the Covid-19 Pandemic
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Background: High-titer neutralizing anti-cytokine autoantibodies have been shown to be involved in several acquired diseases, including pulmonary alveolar proteinosis, cryptococcal meningitis, and disseminated/extrapulmonary Nocardia infections (anti-GM-CSF autoantibodies), disseminated mycobacterial disease (anti-IFN-gamma autoantibodies), and some cases of severe COVID-19 infection (anti-type 1 interferons). Currently, patient blood samples are shipped via courier and require temperaturecontrolled conditions for transfer. This method is expensive and requires patients to have access to medical personnel to draw the blood. However, the well-established technique of collecting blood on a paper card as a dried blood spot (DBS) for diagnosis offers a point of care alternative which can be performed with a simple finger prick. This method is less invasive, cheaper, and allows for easy transport of patient samples. Method(s): 30 uL of whole blood from patients was blotted on filter paper and stored at 4C until use. The filter paper was hole punched and each punched spot was eluted with 150 uL of a 0.05% Tween PBS solution at room temperature overnight. The eluate was screened for anti-cytokine autoantibodies using a particle-based approach. Patient plasma was also screened in conjunction for comparison. Result(s): We confirmed the presence of autoantibodies in the DBS eluate from 4 previously diagnosed patients with anti-GM-CSF autoantibodies and 2 patients with anti-IFN-gamma autoantibodies. Functional studies showed the DBS eluate from a patient with anti-GM-CSF autoantibodies was able to block GM-CSF-induced STAT-5 phosphorylation in normal PBMC. As a proof of concept and to increase the number of patients evaluated, we also confirmed the presence of anti-cytokine autoantibodies using dried plasma eluate from 9 patients with known anti-GM-CSF autoantibodies and 9 patients with anti-IFN-gamma autoantibodies. Levels detected in DBS analyses were comparable to the levels found in plasma from the same patients not subjected to blotting and elution. Temperature studies showed that the autoantibodies were detected at similar levels when stored at 4C, 25C, and 40C for a week. Conclusion(s): The diagnosis of pathogenic anti-cytokine autoantibodies should be considered in the context of unusual or adult-onset infections, and screening for this diagnosis can be performed with dried blood spot testing.Copyright © 2023 Elsevier Inc.
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Mangrove tourism is one of the tourist destinations offered by tourism managers that is currently gaining popularity and popularity among tourists. Keeping tourists coming back can be a very effective strategy for developing tourist destinations. This study employs Experiential Marketing as a strategy to increase tourist interest. Because research in the field of experiential marketing in nature tourism destinations such as mangrove tourism is still limited, the topics of this study are experiential marketing and visitor visit intention. The purpose of this study was to determine the impact of strategic experiential modules (SEMs) on visitor revisits intention. The research method used is quantitative with the variable dimensions of SEMs and visitor revisits intention, a sample of 93 tourists with a purposive sampling technique, and multiple linear regression analysis techniques. The results showed that the sense, act, and relate variables had a positive and significant impact on the visitor revisits intention, while the feel variable had a positive but not significant impact, and the think variable had a negative but not significant impact on the visitor revisits intention.
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This study aimed to optimize the line managers performances in the human resources (HR) division in answering the role of the HR management function problem in Medan City Manufacturing Company. The novelty proposed is a concept of HR management called "Human Resources Professional Transformation". Specifically, this concept discussed the ability of HR division line managers to make adaptive changes to the company's business-oriented functional divisions with managerial competence, commitment, innovation capability, and readiness for changes towards work performance. The population of this research was the line manager of the HR division, totaling 185 respondents. The sampling technique used a probability sampling approach with simple random sampling through the slovin formula, totaling 126 respondents. The analytical tool used is structural equation software through the SmartPLS application program. The results showed that managerial competence, commitment, innovation capability had a positive and significant effect through the HR professional transformation on the performance of line managers in the HR division. Meanwhile, readiness for change has a positive and insignificant effect on the HR Professional Transformation. Readiness for change also has a positive and insignificant effect on the Line Managers Performances in the Human Resources Division through HR Professional Transformation. Based on the suitability test of the research model, it proved that the HR Professional Transformation can answer the problem of the role of the management function to improve the line managers performances in the HR division with managerial competence, commitment, innovation capability, and readiness for change of 0.907.
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There was a change in the environment and food security threat during the COVID-19 pandemic. Many countries, including Indonesia, are forced to allocate funds to reduce the risk of this disaster. The Government Republic of Indonesia, through the Ministry of Social Affairs, has launched a Social Cash Assistance Program for 10 million families affected by COVID-19. This study aims to identify how families affected by COVID-19 take advantage of this social cash assistance. The study was conducted on the beneficiaries of social assistance, in cash transfer of IDR 600,000 (USD 40), per month, for three months. This study involved 2290 beneficiaries as respondents spread across 12 provinces. The sampling technique was the Cohen Manion Morrison Table by proportional stratified random sampling. The findings show that (1) 99% of cash assistance is used for basic needs, especially for food, and (2) cash assistance could be used for basic needs for around two to three weeks, thereby strengthening food security. Recommendations are submitted based on the results of this study related to social cash assistance and food security. The first is that this assistance still needs to be continued until the COVID-19 pandemic is over. It is to help families affected by the COVID-19 pandemic meet their daily needs. Second, most respondents do not have a fixed income during the pandemic, so providing capital and business startups are needed to increase family income sustainably to maintain food security.
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Introduction: The covid-19 disease can be prevented, including by knowledge and public compliance, especially with adolescents in efforts to prevent Covid-19 disease. A preliminary survey of 40 adolescents showed that 30% of teenagers are knowledgeable and 60% of teenagers in Bangkalan are non-compliant in covid-19 prevention efforts. This study aimed to determine the level of compliance to prevent Covid-19. Methods: This research was conducted using a quantitative descriptive survey method. The population and sample were taken by simple random sampling, namely, all adolescents aged 14-21 years in Bangkalan as many as 200 respondents. The instrument uses a questionnaire about Covid-19 prevention efforts. Quantitative data analysis by calculating the frequency of values in a variable. Results: The results showed that 66% of adolescents washed their hands, 95.5% stated that they already knew how to wash their hands properly, and 96.5% used clean water and soap to wash their hands. All adolescents still leave the house, 46% avoid crowds and 97% have kept their distance. 96.5% of adolescents used masks when leaving the house. 84.5% of respondents exercised during a pandemic. 64% of respondents consume nutritious food, exercise, and add vitamins to maintain their immunity, and 59% wear masks, wash their hands and keep a suitable distance health protocol as an effort to prevent Covid-19. Conclusion: The level of adolescent adherence is very good in terms of all aspects of the efforts to prevent Covid-19 except for the physical distancing aspect, so there is a need for increased socialization to eliminate the stigma about physical distancing. [ FROM AUTHOR] Copyright of Malaysian Journal of Medicine & Health Sciences is the property of Universiti Putra Malaysia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)
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This paper is to investigate the extent and speed of the spread of the coronavirus disease 2019 (COVID-19) pandemic in the United States (US). For this purpose, the fractional form of the susceptible-exposed-infected-recovered-vaccinated-quarantined-hospitalized-social distancing (SEIR-VQHP) model is initially developed, considering the effects of social distancing, quarantine, hospitalization, and vaccination. Then, a Monte Carlo-based back analysis method is proposed by defining the model parameters, viz. the effects of social distancing rate (α), infection rate (β), vaccination rate (ρ), average latency period (γ), infection-to-quarantine rate (δ), time-dependent recovery rate (λ), time-dependent mortality rate (κ), hospitalization rate (ξ), hospitalization-to-recovery rate (ψ), hospitalization-to-mortality rate (ϕ), and the fractional degree of differential equations as random variables, to obtain the optimal parameters and provide the best combination of fractional order so as to give the best possible fit to the data selected between January 20, 2020 and February 10, 2021. The results demonstrate that the number of infected, recovered, and dead cases by the end of 2021 will reach 1.0, 49.8, and 0.7 million, respectively. Moreover, the histograms of the fractional order acquired from back analysis are provided that can be utilized in similar fractional analyses as an informed initial suggestion. Furthermore, a sensitivity analysis is provided to investigate the effect of vaccination and social distancing on the number of infected cases. The results show that if the social distancing increases by 25% and the vaccination rate doubles, the number of infected cases will drop to 0.13 million by early 2022, indicating relative pandemic control in the US. [ FROM AUTHOR] Copyright of Fractals is the property of World Scientific Publishing Company and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)
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The TG6002.03 trial is a dose-escalation phase 1 clinical trial of TG6002 infusion via the hepatic artery in patients with liver-dominant colorectal cancer metastases. TG6002 is an engineered Copenhagen strain oncolytic Vaccinia virus, deleted of thymidine kinase and ribonucleotide reductase to enhance tumor selective viral replication and expressing FCU1, an enzyme converting the non-cytotoxic prodrug 5-fluorocytosine (5-FC) into the chemotherapeutic compound 5-fluorouracil (5-FU). In this trial, patients with advanced unresectable liver-dominant metastatic colorectal cancer who had failed previous oxaliplatin and irinotecan-based chemotherapy were treated with up to 2 cycles of TG6002 infusion 6 weeks apart via the hepatic artery on day 1 combined with oral 5-FC on days 5 to 14 (where day 1 = TG6002 infusion). TG6002 infusion was performed over 30 minutes via selective catheterization of the hepatic artery proper. 5-FC oral dosing was 50mg/kg x4 daily. Blood was sampled for TG6002 pharmacokinetics and 5-FC and 5-FU measurements. Sampling of liver metastases was performed at screening and on day 4 or day 8 for virus detection and 5-FC and 5-FU quantification. In total, 15 patients (median age 61 years, range 37-78) were treated in 1 UK centre and 2 centres in France and received a dose of TG6002 of 1 x 106 (n=3), 1 x 107 (n=3), 1 x 108 (n=3), or 1 x 109 pfu (n=6). Fourteen of the 15 patients received a single cycle of treatment, including one patient who did not received 5-FC, and one patient received two cycles. TG6002 was transiently detected in plasma following administration, suggesting a strong tissue selectivity for viral replication. In the highest dose cohort, a virus rebound was observed on day 8, concordant with replication time of the virus. In serum samples, 5-FU was present on day 8 in all patients with a high variability ranging from 0.8 to 1072 ng/mL and was measurable over several days after initiation of therapy. Seven of the 9 patients evaluable showed the biodistribution of the virus in liver lesions by PCR testing on day 4 or day 8. Translational blood samples showed evidence for T-cell activation and immune checkpoint receptor-ligand expression. At 1 x 109 pfu, there was evidence for T-cell proliferation and activation against tumour-associated antigens by ELISpot and for immunogenic cell death. In terms of safety, a total of 34 TG6002-related adverse events were reported, of which 32 were grade 1-2 and 2 were grade 3. The maximum tolerated dose was not reached, and a single dose-limiting toxicity was observed consisting of a myocardial infarction in a context of recent Covid-19 infection in a 78-year-old patient. These results indicate that TG6002 infused via the hepatic artery in combination with oral 5-FC was well tolerated, effectively localized and replicated in the tumor tissues, expressed its therapeutic payload and showed anti-tumoral immunological activity.
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The United Nations Secretary-General Mechanism (UNSGM) for investigation of the alleged use of chemical and biological weapons is the only established international mechanism of this type under the UN. The UNGSM may launch an international investigation, relying on a roster of expert consultants, qualified experts, and analytical laboratories nominated by the member states. Under the framework of the UNSGM, we organized an external quality assurance exercise for nominated laboratories, named the Disease X Test, to improve the ability to discover and identify new pathogens that may cause possible epidemics and to determine their animal origin. The "what-if" scenario was to identify the etiological agent responsible for an outbreak that has tested negative for many known pathogens, including viruses and bacteria. Three microbes were added to the samples, Dabie bandavirus, Mammarenavirus, and Gemella spp., of which the last two have not been taxonomically named or published. The animal samples were from Rattus norvegicus, Marmota himalayana, New Zealand white rabbit, and the tick Haemaphysalis longicornis. Of the 11 international laboratories that participated in this activity, six accurately identified pathogen X as a new Mammarenavirus, and five correctly identified the animal origin as R. norvegicus. These results showed that many laboratories under the UNSGM have the capacity and ability to identify a new virus during a possible international investigation of a suspected biological event. The technical details are discussed in this report.Copyright © 2022
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BACKGROUND: According to the results of the ESSE-RF study, the frequency of obesity in the population reached 29.7%. Obesity is one of the main risk factors for the development of cardiovascular diseases. Features of the course of COVID-19 in patients with obesity is a very urgent problem. AIM: The aim of the study was a comparative investigation of clinical and laboratory-instrumental parameters in AH patients with or without obesity who had COVID-19 associated pneumonia, to identify the role of obesity as a potential predictor of post-COVID cardiovascular complications 3 months after discharge from the hospital. MATERIALS AND METHODS: Materials and methods. The study included 174 patients with COVID-19-associated pneumonia. Group 1 included 78 patients with AH without obesity, group 2 - 96 patients with AH and obesity. All patients were tested with a blood sample at the time of admission and 3 months after discharge from the hospital. We assessed parameters of general blood test, biochemistry, hemostasis, inflammation biomarkers - concentration of C-reactive protein (CRP), highly sensitive CRP (hs-CRP), homocysteine, IL-6, etc. All patients initially underwent computed tomography of the chest. In both groups, 24-hour blood pressure monitoring was performed using BPLaB device, according to the standard protocol;echocardiography using an expert class ultrasound diagnostic system Vivid S70. The study is registered with the Clinical Trials.gov database Identifier: NCT04501822. RESULT(S): Results. The biomarker that significantly distinguished the both groups of patients, as well as subgroups according to the degree of obesity was the concentration of maxCRP and hs-CRP, which was significantly higher in group 2. In addition, the registered maximum values of MPO, NT-proBNP, IL-1,6, TNA-alpha and NRL parameters in group 2 of patients with 2-3 degrees of obesity, may indicate the highest probability of developing delayed adverse cardiovascular complications in this group of patients. Mean systolic blood pressure, variability of systolic and diastolic blood pressure, and heart rate at night were significantly higher in AH patients with obesity. Numerous correlations of obesity with laboratory and instrumental parameters have been registered, which may indicate an increased likelihood of delayed unwanted cardiovascular complications in this particular group of patients. Multiple regression showed that obesity is an independent predictor of an increase in LDH, hs-CRP and right atrium. CONCLUSION(S): Dynamic control of the studied parameters in patients with AH and OB registered an increased concentration of CRP at the initial stage and 3 months after treatment, with a general trend towards a decrease in the increased initial structural parameters of ECHO CG. The logistic regression method showed that the presence of OB in patients with AH is an independent factor causing increased levels of immune inflammation (CRP), a marker of tissue destruction (LDH), and load on the right atrium.Copyright © Endocrinology Research Centre, 2022.
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Background & Aim: Adoptive T cell immunotherapy holds great promise for the treatment of viral complications. Our group has been developing and trialling virus-specific T cell therapies for more than 20 years. Recently, we have generated a repository of multi-virus-specific T cells for our clinical trials. Unfortunately, for many patients with viral complications, there is no suitable trial through which to access these therapies. In Australia, the Therapeutic Goods Administration has a Special Access Scheme (SAS) to enable provision of unapproved therapies for compassionate use. Our research group is now a leading Australian provider of "off-the-shelf" and custom-grown allogeneic virus-specific T cells to hospitals for patients with no other treatment options. Methods, Results & Conclusion(s): We have generated a repository of multi-virus-specific T cells from 20 healthy donors, with up to 150 doses of T cells per donor generated from a single blood sample. Each product batch is thoroughly characterised in terms of viral antigen specificity, HLA restriction and alloreactivity. These T cells target a combination of Epstein-Barr virus, cytomegalovirus, BK polyomavirus, John Cunningham virus and adenovirus epitopes. We have also generated a repository of SARS-CoV-2-specific T cells and occasionally grow custom patient-specific batches of T cells from nominated donors, on request. Since 2008, we have provided virus-specific T cells to 15 hospitals across Australia, and the volume of supply requests has significantly increased in recent years, as clinicians have gained interest in adoptive immunotherapy. In 2022, we provided T cells for 26 patients via the SAS. The majority were experiencing post-transplant complications, including cytomegalovirus disease, BK virus-associated haemorrhagic cystitis and post-transplant lymphoproliferative disorder. Through our clinical trials, we have developed rigorous processes for T cell therapy manufacture and characterisation, in addition to a computer-based selection algorithm, which we apply to SAS cases. As these cases are not part of a clinical trial, concomitant therapy varies, and monitoring is not uniform. However, we have received reports of clinical benefit from adoptive T cell therapy. These include cases of reduction in viral load, improvement in symptoms, and complete resolution of infection. We believe that these promising T cell therapies should be available to hospitals through a nationally funded centre for cellular therapies for critically ill patients.Copyright © 2023 International Society for Cell & Gene Therapy
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e-Employee Discipline is the electronic and remote conduction of employee discipline procedure during the COVID-19 pandemic. This study is a quantitative descriptive study that focused on assessing and analyzing the implementation of e-Employee Discipline Procedure. Convenient purposive sampling technique was assigned to 150 employees who were employed during COVID-19 pandemic in Metro Manila as the respondents in this study. Furthermore, a survey was utilized to gather quantitative data. Moreover, a one-on-one interview using the data gathered in the statistical result was utilized to gather qualitative data. The demographic profile, majority are male (60%) who age 22 to 25 years old (34%), who are college graduates (48.7%), having an entry level job position (46.7%) and working in art/media/communication industry (35.3%) during the COVID-19 pandemic. The respondents find that the implementation of the e-Employee Discipline Procedure as fair and effective in terms of proper documentation procedures, handling of confidentiality, safety and security ( = 4.64;σ = 0.68). However, the challenge is that the respondents moderately agree that the procedure of employee discipline that is conducted remotely is somehow a bit far off with what is usually done in the office (face-to-face) ( = 4.38;σ = 1.30). The absence of physical touch and non-verbal cues like tone of voice, body language and hand gesture are something that the respondents are longing for. Pandemic really detached people from the warmth of each other. Conducting employee discipline which oftentimes has dealt with emotions remotely finds the respondents longing for the physical presence of being heard. © 2023 ACM.
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Introduction: The COVID-19 pandemic significantly impacted the global teaching and learning process (TnL). Unfortunately, to date, not many qualitative studies have been published specifically on the impact of COVID-19 on the Family Medicine course, particularly in Malaysia. Hence, this study aimed to explore the impact of COVID-19 pandemic on the teaching and learning experience of undergraduate students undergoing their Family Medicine course at a local university. Methods: A qualitative study using focused group discussion (FGD), was conducted among undergraduate students during the lockdown period. A semi-structured interview guide was used to interview 20 students, in their fifth undergraduate year, undertaking their fourth to fifth week of a total six-week course. They were selected using purposive snowball sampling method. There were four focus group discussions (FGD) with five students in a group. All interviews were audio-taped, transcribed verbatim, and the contents were analysed using the standard content analysis framework. Subsequently, thematic content analysis was conducted, and three major themes were produced. Results: The three major themes were (1) facilitators to learning, (2) barriers to learning, and (3) rooms for improvement. Conclusion: Although COVID-19 pandemic had significant impact on TnL of Family Medicine course among undergraduates, the students remained optimistic and proposed some improvement from their point of view. However, a creative, realistic, effective, and impactful way of TnL, particularly in clinical aspects should be developed and experimented. Technological progress and advancement should permit this idea to be achievable and implemented in near future. [ FROM AUTHOR] Copyright of Malaysian Journal of Medicine & Health Sciences is the property of Universiti Putra Malaysia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)
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Background/Objectives: During COVID-19 pandemic, it is essential to detect patients potentially at risk of life-threatening complications, due to possible specific genetic mutations. The aim of our work is to show a practical application of genetic testing, allowing a diagnosis of alpha 1 antitrypsin deficiency in cases with a severe clinical course during COVID-19 infection. Method(s): During hospitalization for COVID-19, we identified 5 patients (3 female, 2 males from two different families, age range 18-47 years) with a severe course of COVID-19 infection, requiring high pressure ventilation with high volume oxygen supply. Two months after discharge, those patients were reevaluated with respiratory function tests, biochemical tests, genetic counselling and genetic testing. A peripheral blood sampling for SERPINA1 genetic testing has been performed, using Sanger sequencing. Result(s): Two months after discharge, in all 5 patients respiratory function tests were consistent with a dysventilatory obstructive syndrome, in contrast with usual findings related to COVID-19 infection. Blood test still showed increase plasmatic transaminase concentration in 3 out of 5 patients, one having increased serum bilirubin as well. We performed SERPINA1 genetic testing showing homozygosity for SERPINA1 pathogenic mutations (c.193del and c.875C>T, respectively) in all 5 patients. Conclusion(s): These cases showed the importance of genetic testing for patients with unexplained severe COVID-19 infection. Genetic testing allowed the diagnosis of cases affected by alpha 1 antitrypsin deficiency, associated with dysventilatory obstructive syndrome, that may worsen the short and long term prognosis of COVID-19.
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Cancer patients, particularly those receiving B cell-depleting therapy for lymphoid malignancies, are at risk of prolonged SARS-CoV-2 infection, poorer clinical outcomes, and delayed initiation or disruption of cancer-directed therapy (Lee at al., 2022, Clark et al., 2021). We first studied T-cell mediated response to the Wuhan strain of SARS-CoV-2 in a cohort of 69 patients with hematologic and solid cancers, including 18 patients who received prior B-cell depleting therapy. Patients with prolonged COVID-19 clearance, defined by a positive PCR test for longer than 30 days, had a broad but poorly converged CD8+ dominant response and a lacking CD4+ response. To conduct this analysis, we performed bulk T-cell receptor (TCR) sequencing of 121 blood samples and tracked over time TCR repertoire statistics such as clonality, convergence, breadth, and depth of COVID-19-associated TCRs during the active and convalescent periods of COVID-19 infection. These SARS-CoV-2-associated TCRs were identified leveraging immunoSEQ T-MAP database (Snyder et al., 2020), a set of TCR sequences derived from COVID-19 patients and experimentally identified as responsive to MHC Class I and II epitopes from the Wuhan SARS-CoV-2 strain using the multiplex identification of TCR antigen assay (Klinger et al., 2015). To extend our TCR repertoire analysis to other SARS-CoV-2 variants, including Omicron, we developed a deep learning (DL) method to predict TCR specificities for new SARS-CoV-2 epitopes. This DL approach also permits the identification of SARS-CoV2-responsive TCRs private to an individual. Combining this DL approach with our TCR statistics methodology, we studied the dynamics of T-cell response to COVID-19 vaccinations in a cohort of 50 patients with cancer and analyzed TCR repertoire characteristics associated with different degrees of COVID-19 severity in a cohort of 42 cancer patients who contracted the Omicron. Understanding cellular response to novel infections is critical for patient care in the context of cancer, and our novel DL-based approach can leverage existing datasets to analyze and track response to emerging viral strains.
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During the COVID-19 epidemic, blood samples are usually processed at 56 to attenuate the virus before pathogen detection. 71 blood samples of malaria patients reported by Shanghai Center for Disease Control and Prevention in 2017-2019 were collected, including 38 with Plasmodium falciparum infection, 8 P. malariae, 11 P. ovale and 14 P. vivax. The effect of inactivation on the thermal stability of P. falciparum histidine rich protein II (PfHRPII) and Plasmodium lactate dehydrogenase (pLDH) in blood samples was assessed before and after incubation at 56 for 30 min using the rapid diagnostic test (RDT) kit. The results showed that among the 38 P. falciparum T1-positive (PfHRPII) blood samples before heat treatment, 35 samples remained to be T1-positive (92.11%, 35/38, chi2=3.123, P>0.05) after heat treatment;while 54 blood samples (26 P. falciparum, 6 P. vivax, 10 P. ovale and 12 P. vivax) that were T2-positive (pLDH) before heat treatment turned to be T2-negative (positive rate 0, 0/54, chi2=87.755, P<0.01) after heat treatment. It was demonstrated that PfHRPII is stable during incubation at 56 for 30 min, while pLDH is unstable and degraded or inactivated during the heating. Therefore, the detection results of P. falciparum will not be affected by RDT, but diagnosis of the parasites other than P. falciparum in blood samples may be missed.Copyright © 2021, National Institute of Parasitic Diseases. All rights reserved.
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Introduction Patients with hematological malignancies, including multiple myeloma (MM), experience suboptimal responses to SARS-CoV-2 vaccination. Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM) are precursors to MM and exhibit altered immune cell composition and function. The SARS-CoV-2 pandemic and the subsequent population-wide vaccination represent an opportunity to study the real-life immune response to a common antigen. Here, we present updated results from the IMPACT study, a study we launched in November 2020 to characterize the effect of plasma cell premalignancy on response to SARS-CoV2 vaccination (vx). Methods We performed: (i) ELISA for SARS-CoV-2-specific antibodies on 1,887 peripheral blood (PB) samples (237 healthy donors (HD), and 550 MGUS, 947 SMM, and 153 MM patients) drawn preand post-vx;(ii) single-cell RNA, T cell receptor (TCR), and B cell receptor (BCR) sequencing (10x Genomics) on 224 PB samples (26 HD, and 20 MGUS, 48 SMM, and 24 MM patients) drawn preand post-vx;(iii) plasma cytokine profiling (Olink) on 106 PB samples (32 HD, and 38 MGUS and 36 SMM patients) drawn pre- and post-vx;and (iv) bulk TCR sequencing (Adaptive Biotechnologies) on 8 PB samples from 4 patients (2 MGUS, 2 SMM) drawn pre- and post-vx. Results Patients with MGUS and SMM achieved comparable antibody titers to HD two months post-vx. However, patient titers waned significantly faster, and 4 months post-vx we observed significantly lower titers in both MGUS (Wilcoxon rank-sum, p=0.030) and SMM (p=0.010). These results indicate impaired humoral immune response in patients with MGUS and SMM.At baseline, the TCR repertoire was significantly less diverse in patients with SMM compared to HD (Wilcoxon rank-sum, p=0.039), while no significant difference was observed in the BCR repertoire (p=0.095). Interestingly, a significant increase in TCR repertoire diversity was observed post-vx in patients with SMM (paired t-test, p=0.014), indicating rare T cell clone recruitment in response to vaccination. In both HD and patients, recruited clones showed upregulation of genes associated with CD4+ naive and memory T cells, suggesting preservation of the T cell response in SMM, which was confirmed by bulk TCR-sequencing in 4 patients.Lastly, by cytokine profiling, we observed a defect in IL-1beta and IL-18 induction post-vx in patients with SMM compared to HD (Wilcoxon rank-sum, p=0.047 and p=0.015, respectively), two key monocyte-derived mediators of acute inflammation, suggesting an altered innate immune response as well. Conclusion Taken together, our findings highlight that despite the absence of clinical manifestations, plasma cell premalignancy is associated with defects in both innate and adaptive immune responses. Therefore, patients with plasma cell premalignancy may require adjusted vaccination strategies for optimal immunization.
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Medical waste has been excessively generated in various medical facilities due to COVID-19, and its treatment has become an important concern. Previously, an optimized medical waste sterilization and shredding system was developed for hospital scale but due to increased demand, it is necessary to scale such a system for different facilities. Therefore, in this paper, a sensitivity analysis for the design variables of the shredding system has been conducted and a surrogate model is developed for stress estimation. The surrogate model was generated using LHS (Latin hypercube sampling), which can represent the overall information of the design domain with a limited number of samples. The surrogate model was then used to increase the number of samples for sensitivity analysis which helped in reducing the computational time for finite element analysis. The sensitive variables for the shredder system were then estimated using sensitivity analysis. Consequently, an efficient design framework for various capacities of medical waste shredder was suggested using sensitivity analysis and a data-driven surrogate model.
ABSTRACT
Objective: To determine the diagnostic accuracy of elevated C reactive protein (CRP) and ferritin in predicting severe Covid-19 infection using the World Health Organization's (WHO) Covid-19 severity classification as gold standard. Study Design: Descriptive study. Place and Duration of Study: This study was conducted at the Pak Emirates Military Hospital, Rawalpindi, from January 1st 2021 till April 30th 2021. Ethical review committee's (ERC) approval was taken and good clinical practice guidelines were followed. Material(s) and Method(s): Baseline blood samples were sent to the hospital laboratory for the measurement of C reactive protein and ferritin levels. PCR was taken as gold standard for the diagnosis of Corona virus disease. Patients were classified into severe and non-severe categories using WHO classification of severity. Sensitivity, specificity, diagnostic accuracy, negative predictive value and positive predictive value were calculated for elevated CRP and ferritin. Result(s): There were 65 (57.5%) patients who had severe Covid-19 disease and 48 (42.5%) patients who had non-severe Covid-19 disease. Among the patients with severe Covid-19, 57 (87.7%) had elevated CRP levels, and 50 (76.9%) patients had elevated ferritin levels. Testing ferritin levels, against the severity of Covid-19 patients, there was a sensitivity of 76.9%, specificity of 79.2%, positive predictive value (PPV) of 83.3%, negative predictive value (NPV) of 71.7% and diagnostic accuracy of 77.8%. Testing CRP levels, there was a sensitivity of 87.7%, specificity of 85.4%, PPV of 89.1%, NPV of 83.6% and diagnostic accuracy of 86.7%. Conclusion(s): The results from our study show that CRP has a slightly improved diagnostic accuracy as compared to ferritin. However, both these markers have value in the prediction of severity of Covid-19 infection.Copyright © 2023 Lahore Medical And Dental College. All rights reserved.