ARTICLE | doi:10.20944/preprints201905.0363.v3
Online: 24 September 2019 (11:06:33 CEST)
The 24 September 2001 College Park, Maryland, tornado was a long-track and strong tornado that passed within a close range of two Doppler radars. It was the third in a series of three tornadoes associated with a supercell storm that developed in Stafford County, Virginia, and initiated 3 - 4 km southwest of College Park and dissipated near Columbia, Howard County. The supercell tracked approximately 120 km and lasted for about 126 minutes. This study presents a synoptic and mesoscale overview of favorable conditions and forcing mechanisms that resulted in the severe convective outbreak associated with the College Park tornado. Results show many critical elements of the tornadic event, including a negative-tilted upper-level trough over the Ohio Valley, a jet stream with moderate vertical shear, a low-level warm, moist tongue of the air associated with strong southerly flow over south-central Maryland and Virginia, and significantly increased convective available potential energy (CAPE) during the late afternoon hours. A possible role of the urban heat island effects from Washington, DC in increasing CAPE for the development of the supercell is discussed. Satellite imagery reveals banded convective morphology with high cloud tops associated with the supercell that produced the College Park tornado. Operational WSR-88D data exhibits a high reflectivity “debris ball” or tornadic debris signature (TDS) within the hook echo, the evolution of the parent storm from a supercell structure to a bow echo, and a tornado cyclone signature (TCS). Many of the mesoscale features could be captured by contemporary numerical model analyses. This study concludes with a discussion of the effectiveness of the coordinated use of satellite and radar observations in the operational environment of nowcasting severe convection.
ARTICLE | doi:10.20944/preprints202206.0045.v2
Subject: Earth Sciences, Atmospheric Science Keywords: Satellite meteorology; severe thunderstorms; downbursts; derechos
Online: 15 July 2022 (09:55:51 CEST)
Severe windstorms resulting from mesoscale convective systems (MCS) cause significant disruption to society, including widespread power outages, tree and structural damage, and transportation accidents that affect multi-state regions and metropolitan areas along their track. A derecho, defined as a long-lived, widespread severe convective windstorm, is composed of numerous downbursts (intense localized storm downdrafts) organized into clusters or families of clusters. Derechos can produce winds above hurricane force along a track that may exceed several hundred kilometers. Convective windstorm potential has been expressed as a grouping of stability parameters that are relevant for downburst generation. These include lower-to-mid-tropospheric and equivalent potential temperature (θe) lapse rates, vertical relative humidity differences, and the amount of convective available potential energy (CAPE) in the troposphere. One major environmental factor addressed in the generation of widespread severe convective winds is an elevated mixed layer and its associated instability that promotes powerful storm updrafts and downdrafts. Another critical factor is developing a rear-inflow jet into an MCS that channels unsaturated mid-tropospheric air into the leading convective storm line. Establishing an elevated, ascending front-to-rear flow originating from deep, moist convection, overlying a strong and deep outflow-induced cold pool has been found to generate and sustain a robust rear inflow jet. The North American Derecho of 29-30 June 2012 exhibits many classic progressive and serial derecho features. It remains as one of the highest-impact derecho-producing convective systems (DCS) over CONUS since 2000. This research effort enhances the understanding of the science of operational forecasting of severe windstorms through examples of employing new satellite and ground-based microwave and vertical wind profile data. During the track of the derecho from the upper Midwestern U.S. through the mid-Atlantic region on 29 June 2012, clear signatures associated with a severe MCS were apparent in polar satellite imagery, especially from the EPS METOP-A Microwave Humidity Sounder (MHS), Defense Meteorological Satellite Program (DMSP) Special Sensor Microwave Imager Sounder (SSMIS) and NASA TERRA Moderate Resolution Imaging Spectroradiometer (MODIS). In addition, morning (descending node) and the evening (ascending node) METOP-A Infrared Atmospheric Sounding Interferometer (IASI) soundings are compared to soundings from surface-based Radiometrics Corporation MP-3000 series microwave radiometer profilers (MWRPs) along the track of the derecho system. The co-located IASI and MWRP soundings revealed a pre-convective environment that indicated a favorable volatile tropospheric profile for severe downburst wind generation. An important outcome of this study will be to formulate a functional relationship between satellite-derived parameters and signatures, and severe convective wind occurrence. In summary, a comprehensive approach to observational data analysis involves both surface- and satellite-based instrumentation. Because this approach utilizes operational products available to weather service forecasters, it can feasibly be used for monitoring and forecasting local-scale downburst occurrence within derecho systems, as well as larger-scale convective wind intensity associated with the entire DCS.
ARTICLE | doi:10.20944/preprints202203.0072.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: antibiotic resistance; Acinetobacter baumannii; severe pneumonia
Online: 4 March 2022 (03:15:35 CET)
Background: Patients hospitalized in the intensive care unit (ICU) have a higher susceptibility to infections. Respiratory infections are the most common nosocomial infections. Rising antibiotic resistance due to indiscriminate use of antibiotics and poor adherence to standard precaution in healthcare facilities compounds the problem. The main aim of this study is to assess microbial patterns and antibiotic resistance from bronchoalveolar lavage specimens in severe pneumonia patients. Methods: This retrospective study was conducted in an Indonesian tertiary care hospital from January 2016-December 2020. Written and verbal informed consent was obtained prior to bronchoscopy procedures. Patients were enrolled if they had severe community-acquired pneumonia (CAP) according to American Thoracic Society (ATS)/Infectious Disease Society of America (IDSA) criteria, had high-risk hospital-acquired pneumonia (HAP), late-onset ventilator-associated pneumonia (VAP), or pneumonia caused by Coronavirus disease (COVID-19). Respiratory specimens via bronchoscopy were inoculated on general semi-sloid thioglycolate media. Testing for antibiotic susceptibility was done using the disk diffusion method. Results: Two hundred and one patients’ data were analyzed. The majority of patients were males (65,17%) and above 60 years of age. The most common type of pneumonia was CAP (39,3%). Neurologic/cerebrovascular disease was the most common comorbidity (35,32%). Acinetobacter baumannii was the most frequently isolated microorganism. Ampicillin/sulbactam and amikacin were found to yield lower microbial resistance. Conclusion: Combination of ampicillin/sulbactam and amikacin appeared effective as initial empirical therapy in severe pneumonia patients. Further studies are needed to evaluate the feasibility and effectiveness of this combined therapy.
ARTICLE | doi:10.20944/preprints201611.0005.v2
Online: 3 November 2016 (08:39:30 CET)
Severe early childhood caries remains the most common chronic disease affecting children. Its multifactorial etiology has established a controversy about which risk factors were more significant to its development. Therefore our study aimed through meticulous statistical analysis to arrange the “well agreed upon” common risk factors in order of significance, to aid the clinician in tailoring an adequate preventive program for this affected age group. The study reshuffled the risk factors contributing to severe early childhood caries and placed them in the order of their significance as follows: snacking of sugary food several times a day, increased number of siblings to 3 or more, night feeding, child self-employed brushing, mother caries experience, 2 siblings, on demand feeding, once/day sugary food, sharing utensils, 1 Sibling, male gender, father’s education, late first child dental visit, brushing time, mother’s education, no dental visit, decreased brushing frequency & no night brushing.
ARTICLE | doi:10.20944/preprints201610.0130.v1
Subject: Materials Science, Nanotechnology Keywords: stainless steel; severe plastic deformation; strength
Online: 31 October 2016 (01:55:15 CET)
Enhancement in the strength of austenitic steels with a small content of carbon can be achieved by a limited number of methods, among which is the ultrafine-grained (UFG) structure formation, especially efficient with the use of severe plastic deformation (SPD) processing that enables increasing significantly the contribution of grain-boundary strengthening, and also involves a combination of other strengthening factors (work hardening, twins, etc.). In this paper, we demonstrate that the use of SPD processing combined with conventional methods of deformation treatment of metals, such as rolling, may lead to an additional strengthening of UFG steel. Analysis of the results of the study on the change of the microstructure and mechanical properties of the Cr-Ni stainless austenitic steel after a combined deformation reveals a substantial increase in the strength properties of this steel, resulting from a consecutive application of SPD processing via equal-channel angular pressing and rolling at a temperature of 400 С, yielding a strength more than 1.5 times higher that that produced by any of these two methods used separately.
Subject: Life Sciences, Genetics Keywords: COVID-19; severe symptoms; inactivation; genetic diversity
Online: 16 April 2020 (09:15:49 CEST)
The rapid spread of the coronavirus disease 2019 (COVID-19) is a serious threat to public health systems globally and is subsequently, a cause of anxiety and panic within human society. Understanding the mechanisms and reducing the chances of having severe symptoms from COVID-19 will play an essential role in treating the disease, and become an urgent task to calm the panic. However, the COVID-19 test developed to identify virus carriers is unable to predict symptom development in individuals upon infection. Experiences from other plagues in human history and COVID-19 statistics suggest that genetic factors may determine the compliance with the virus, i.e., severe, mild, and asymptomatic. Here, a hypothesis is put forward based on the epidemiological characteristics and traits of COVID-19, and our gene expression analysis. It proposes that COVID-19 inactivation in the blood by blocking virus entry into other internal organs for reproduction through the blood circulation after lung cell invasion prevents severe symptoms. Additionally, we investigated a genetic connection between candidate genes and severe COVID-19 symptoms through the utilization of strategies combining hypothesis and data-driven approaches. A list of genes and important SNPs that require further investigation to aid the screening of individuals who may suffer severe illness if exposed to the virus is present. Those individuals should be intensively safeguarded and prioritised for treatment. Concurrently to further research on the COVID-19 pathogenesis, our results also offer a new research strategy for pandemic prevention and health maintenance.
ARTICLE | doi:10.20944/preprints202005.0449.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: retrospective cohort; predictors; recovery; severe acute malnutrition; Jimma
Online: 27 May 2020 (08:59:02 CEST)
Background: Treatment at stabilization center is an important intervention to avert the huge burden of mortality for children with complicated severe acute malnutrition (SAM). Recent reviews indicated a wide range in recovery rate (34-88%) due to several context-specific factors. This study aimed to estimate time to recovery and to determine predictors of time to recovery among children aged 6-59 month with severe acute malnutrition. Method: Retrospective cohort study was used among 375 children aged 6-59 months admitted in Jimma university medical center, from September 2015 to September 2017. Kaplan Meir estimate and survival curve was used to compare the time to recovery using log-rank test among different characteristics. Cox Proportional Hazard Model was used to identify significant predictors of time to recovery. Results: Median time of recovery for cohort of SAM children’s was 19 days (95%CI: 17.95-20.05). Independent predictors of time to recovery were: Play stimulation, vaccination status, Tuberculosis, malaria, use of amoxicillin, deworming and shock. Conclusion: The findings of this study showed that the average length of stay on treatment and median time for recovery are within the sphere standard. Psychosocial stimulation, appropriate provision of routine medication and management of medical co-morbidity are needed to promote fast recovery.
ARTICLE | doi:10.20944/preprints202005.0185.v1
Subject: Materials Science, General Materials Science Keywords: severe plastic deformation; iron hardness; micro/nano-structure
Online: 11 May 2020 (03:33:40 CEST)
The evolution of metals micro/nano-structure upon severe plastic deformation (SPD) is still far to be theoretically explained, while experimental datasets are persistently growing for several decades. Major problem associated with understanding of SPD is related to a fact that the latter is a synergetic product of several competing physical effects which alter the material micro/nano-structure. In attempt to find deformational boundaries, where predominantly one mechanism determines the micro/nano-structure, in this paper we propose a continuous piecewise model for the analysis of experiments on material hardness vs strain of SPD processed materials. The novelty of this approach lies in its ability to find, as free-fitting parameters, the strain breakpoints which separate different micro/nano-structure modes generated upon SPD process. The model is applied to analyse experimental data for polycrystalline samples of pure iron and two distinctive strain breakpoints are revealed with good accuracies. This finding is in a good agreement with our earlier results on TEM microscopy studies on pure iron polycrystals after SPD treatment.
ARTICLE | doi:10.20944/preprints202110.0160.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: allergic severe asthma; anti-IgE; Omalizumab; observational study; children
Online: 11 October 2021 (13:54:56 CEST)
Background: Asthma is the most common chronic disease affecting children and altering their quality of life. The severity of asthma is often modulated by immunoglobulin E (IgE)-mediated allergen sensitization and is associated with comorbid allergic dis-eases. Omalizumab is a humanized monoclonal antibody anti-IgE, the first biological therapy approved to treat patients aged ≥6 years with severe allergic asthma. The primary objective of our study was to investigate the efficacy and safety of Omali-zumab in Romanian paediatric patients with severe allergic asthma. Methods: In this observational real-life study, 12 children aged 6 to 18 years, (mean age 12.4 years ) with severe allergic asthma received Omalizumab as an add-on treatment. The levels of asthma control, exacerbations, lung function and adverse events were evaluated at baseline and after the first year of treatment. Results: We noticed general improvements in total asthma symptom scores and the rate of exacerbation of severe asthma. Omalizumab increased the initial variables of lung function, and no serious adverse reactions were reported. FEV1 improved statistically significant after one year of treatment with Omalizumab, [ΔFEV1 (% pred.) =18.3, and similarly, ΔMEF50 (%) = 25.8]. The mean severe exacerbation rates due to asthma decreased from 4.1 (2.8 SD) to 1.15 (0.78 SD) during the treatment year (p<0.0001) with Omalizumab. Conclusions: Treatment with Omalizumab can be an effective and safe therapeutic option for Romanian children with severe allergic asthma, providing clinically relevant in-formation on asthma control and exacerbation rate in children and adolescents. The results highlighted the effect of Omalizumab in young patients, starting from the first year of treatment.
REVIEW | doi:10.20944/preprints202103.0597.v2
Subject: Medicine & Pharmacology, Allergology Keywords: viral respiratory infections; severe asthma; immune response; biologicals; omalizumab
Online: 26 March 2021 (10:55:06 CET)
Viral respiratory infections are recognized risk factors for the loss of control of allergic asthma and the induction of exacerbations, both in adults and children. Severe asthma is more susceptible to virus-induced asthma exacerbations, especially in the presence of high IgE levels. In the course of immune responses to viruses, an initial activation of innate immunity typically occurs and the production of type I and III interferons is essential in the control of viral spread. However, the Th2 inflammatory environment still appears to be protective against viral infections in general and in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections as well. As for now, literature data, although very limited and preliminary, show that severe asthma patients treated with biologics don’t have an increased risk of SARS-CoV-2 infection or progression to severe forms compared to the non-asthmatic population. Omalizumab, an anti-IgE monoclonal antibody, exerts a profound cellular effect, which is able to stabilize the effector cells becoming much more efficient from the point of view of innate immunity in contrasting respiratory viral infections. In addition to the antiviral effect, clinical efficacy and safety of this biological allows a great improvement in the management of asthma.
ARTICLE | doi:10.20944/preprints201912.0205.v2
Subject: Medicine & Pharmacology, Pediatrics Keywords: diarrhoea; severity; severe dehydration; children; risk factors; Ujjain; India
Online: 16 January 2020 (03:21:03 CET)
Diarrhoea contributes significantly in the under-five childhood morality and mortality worldwide. This cross-sectional study was carried out in a tertiary care hospital in Ujjain, India from July 2015 to June 2016. Consecutive children aged 1 month to 12 years having “some dehydration” and “dehydration” according to World Health Organization classification were eligible to be included in the study. Other signs and symptoms used to assess severe dehydration were capillary refill time, urine output, and abnormal respiratory pattern. A questionnaire was administered to identify risk factors for severe dehydration, which was the primary outcome. Multivariate logistic regression modeling was used to detect independent risk factors for severe dehydration. The study included 332 children, with mean ± standard deviation age of 25.62 ± 31.85 months; out of which, 70%(95% confidence interval [CI] 65 to 75) were diagnosed to have severe dehydration. The independent risk factors for severe dehydration were: child not exclusive breast fed in the first six months of life (AOR 5.67, 95%CI 2.51 to 12.78; p<0.001), history of not receiving oral rehydration solution before hospitalization (AOR 1.34, 95%CI 1.01 to 1.78; p=0.038), history of not receiving oral zinc before hospitalization (AOR 2.66, 95%CI 1.68 to 4.21; p<0.001) and living in overcrowded conditions (AOR 5.52, 95%CI 2.19 to 13.93; p<0.001). The study identified many risk factors associated with severe childhood dehydration; many of them are modifiable though known and effective public health interventions.
ARTICLE | doi:10.20944/preprints202104.0737.v1
Subject: Medicine & Pharmacology, Allergology Keywords: congenital diaphragmatic hernia, severe pulmonary hypertension, bedside surgery, NICU infrastructure
Online: 28 April 2021 (10:06:10 CEST)
Background: This study presents the experience gained in the Newborn Intensive Care Unit (NICU) at “M. S. Curie” Emergency Clinical Hospital for Children in Bucharest after performing a series of bedside surgery interventions on newborns with congenital diaphragmatic hernia (CDH). We evaluate the advantages, complications, immediate and long-term outcome as well as the morbidity. Methods: We conducted a retrospective analysis of the data for all patients operated on-site be-tween 2011 and 2020, in terms of pre- and post-operative stability, procedures performed, com-plications and outcomes. Results: Our study is based on data from ten cases of newborns, term or small for gestation age with birthweights ranging from 2300 to 3300 grams, operated, on average, on the fifth day of life. The main reasons for operating on-site were the hemodynamical instability and the need to ad-minister inhaled Nitic Oxide (iNO) and HFOV ventilation. There were no unforeseen events dur-ing surgery, no immediate postoperative complications and no surgery related mortality. One noticed drawback was the unfamiliarity of the surgery team with the new operating environment. Conclusions: Our experience indicates that bedside surgery improves the likelihood of survival for critically ill neonates suffering from CDH. No immediate complications could be associated with this practice. Keywords: congenital diaphragmatic hernia, severe pulmonary hypertension, bedside surgery, NICU infrastructure
ARTICLE | doi:10.20944/preprints201812.0037.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: neuroplasticity; neuroprogression; psychiatric disorders; brain economy; severe mental illness; biomarkers
Online: 3 December 2018 (16:18:31 CET)
Psychiatric disorders share the same pattern of longitudinal evolution and have courses that tend to be chronic and recurrent. These aspects of chronicity and longitudinal evolution of psychiatric disorders are currently studied under the neuroprogression framework. Interestingly, considering the plasticity of the brain, it is necessary to emphasize the bidirectional nature of neuroprogression. We review evidence highlighting alterations of the brain associated with the longitudinal evolution of psychiatric disorders from the framework of neuroplastic adaptation to pathology. This new framework highlights that substantial plasticity and remodelling may occur beyond the classic neuroprogressive framework, which is characterized only by loss of grey matter volume, decreased brain connectivity, and chronic inflammation. We also integrate the brain economy concept in the neuroplastic adaptation to pathology framework, emphasizing that to preserve its economy, i.e., function, the brain learns how to cope with the disease by adapting its architecture. This approach can disentangle both the specific pathophysiology of psychiatric symptoms and the adaptation to pathology, thus offering a new framework for both diagnosis and treatment.
Subject: Medicine & Pharmacology, General Medical Research Keywords: COVID-19; SARS-CoV-2; coronavirus; severe acute respiratory syndrome coronavirus
Online: 5 July 2020 (10:16:43 CEST)
Background: The information on the difference in clinical characteristics between severe and non-severe cases is limited in some countries including Iran. The objective of this case series is to compare the clinical characteristics, radiologic features, and laboratory findings between COVID-19 severe cases who received the intensive care unit (ICU) care with non-severe cases who did not receive ICU care. Methods: In this retrospective cohort study, 186 laboratory-confirmed patients with COVID-19 diagnosed from 1 March 2020 to 30 March 2020 were investigated. Results: This study population included 186 hospitalized patients with confirmed COVID-19. The median age was 47 years, and 88 (47.31%) were female. Of these patients, 48 were admitted and transferred to ICU. Of 186 patients, 44.62% had medical comorbidities including hypertension and diabetes. The most common clinical manifestation were shortness of breath 86.56%, myalgia 74.19%, and headache. Higher neutrophil counts, CRP, and LDH as well as the lower levels of lymphocytes were the most important laboratory finding among COVID-19 patients. As of April 15, 2020, 33 were still hospitalized. A total of 116 patients (62.70 %) had been discharged, and 36 patients (19.94 %) had died. Of the 48 patients admitted to the ICU, 33.33% have died. Conclusion: In the present study, shortness of breath was the most common clinical symptom, and the mortality rate in patients admitted to the ICU was about 33%, indicating that about one-third of patients with severe illness who admitted to the ICU section died.
ARTICLE | doi:10.20944/preprints202101.0207.v1
Subject: Life Sciences, Biochemistry Keywords: severe fever with thrombocytopenia syndrome; cat; companion animals; viral hemorrhagic fever; pathology
Online: 11 January 2021 (17:48:51 CET)
ABSTRACT: A woman in her 50s showed symptoms of fever, loss of appetite, vomiting, and general fatigue 2 days after she was bitten by a sick cat, which had later died, in Yamaguchi prefecture, western Japan, in June 2016. She subsequently died of multiorgan failure, and an autopsy was performed to determine the cause of death. However, the etiological pathogens were not quickly identified. The pathological features of the patient were retrospectively re-examined, and the pathology of the regional lymph node at the site of the cat bite was found to show necrotizing lymphadenitis with hemophagocytosis. The pathological features were noticed to be similar to those of patients reported to have severe fever with thrombocytopenia syndrome (SFTS). Therefore, the lymph node section was retrospectively tested immunohistochemically for SFTSV antigen, which revealed the presence of SFTSV antigen. The sick cat also showed similar symptoms and laboratory findings similar to those shown in human SFTS cases. It is highly possible that the patient was infected with SFTSV through the sick cat’s bite. If a patient gets sick in an SFTS-endemic region after a cat bite, SFTS should be considered in the differential diagnosis.
REVIEW | doi:10.20944/preprints202003.0353.v1
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: COVID-19; SARS-CoV-2; Severe Acute Respiratory Syndrome Coronavirus-2; Curcumin
Online: 24 March 2020 (03:16:22 CET)
COVID-19 (coronavirus disease 2019) is a public health emergency of international concern caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). As of this time, there is no known effective pharmaceutical, phytopharmaceutical or traditional medicine for cure or prevention of COVID-19, although it is urgently needed. In this review, based on the current understanding of the disease molecular mechanisms of novel Coronavirus SARS-CoV-2 and its closest relative SARS-CoV and other human Coronaviruses, I have identified some naturally occurring plant based substances and Ayurvedic medicinal herbs that could feasibly be tested as a matter of urgency for prevention as well as therapeutic option for COVID-19 in India and other parts of the world. I conclude that dried rhizome of Curcuma longa L. i.e. turmeric, and its active ingredient curcumin may be effective in preventing as well as cure the COVID-19 pandemic due to its proven antiviral activities, this however need to be tested by appropriate clinical trials as research priority.
ARTICLE | doi:10.20944/preprints201904.0041.v1
Subject: Engineering, Civil Engineering Keywords: Terrain‐induced severe wind event; Stratified flows; Computational Fluid Dynamics (CFD); LES
Online: 3 April 2019 (10:39:54 CEST)
In this research, the computational fluid dynamic (CFD) approach that has been used in wind power generation field was applied for the solution of the problems of local strong wind areas in railway fields, and the mechanism of wind generation was discussed. At the same time, the affectivity of the application of computational fluid dynamic approach to railway field was discussed. The problem of local wind that occurs on the railway line in winter was taken up in this research. A computational simulation for the prediction of wind conditions by LES was implemented and it was clarified that the local strong wind area is mainly caused by separated flows originating from the small‐scale terrain positioned at its upstream (at approximately 180.0 m above sea level). Meanwhile, the effects of the size of calculation area and spatial grid resolution on the result of calculation and the effect of atmospheric stability were also discussed. It was clarified that when the air flow characteristic of the separated flow originating from the small‐scale terrain (at altitude of approximately 180.0 m) targeted in this research is reproduced at high accuracy by computational simulation of wind conditions, approximately 10.0 m of spatial resolution of computational grid in horizontal direction is required. As a result of the computational simulation of wind conditions of stably stratified flow (Fr = 1.0), lee waves were excited at the downstream of the terrain over time. As a result, the reverse‐flow region lying behind the terrain that had been observed at a neutral time was inhibited. Consequently, local strong wind area was generated at the downstream of the terrain and the strong wind area passing through the observation mast was observed. By investigating the speed increasing rate of local strong wind area induced at the time of stable stratification, it was found that the wind was approximately 1.2 times stronger than what was generated at a neutral time.
ARTICLE | doi:10.20944/preprints201706.0049.v1
Subject: Engineering, Mechanical Engineering Keywords: ECAP; Tubular channel angular pressing (TCAP); finite element; severe plastic deformation; strains
Online: 12 June 2017 (06:10:57 CEST)
The purpose of this work is to optimize angular extrusion for sever plastic deformation of tubular specimens. A finite element model (FEM) was built in Deform-3D® for three extrusion dies and analyzed. The dies were ECAP (135°), TCAP with external groove of 90° (denoted as TCAP-e) and TCAP with internal groove of 90° (denoted as TCAP-i). The analysis for process parameters (such as coefficient of friction-μ, die angles-ѱ and φ, temperature - T, and radius ratio-R) showed that TCAP-i was the optimal die in processing Al6063 tubes based on strain and load distribution of the model. The TCAP-i die model was further optimized for different parameters namely die angles, coefficient of friction, deformation ratio and temperature. The results showed that at constant process temperature of 25 °C, the optimal TCAP-i has the following parameters: φ2=800, Ѱ1=300, Ѱ2=800, Ѱ3=300, μ =0.4 and R =1.5.
CASE REPORT | doi:10.20944/preprints202201.0298.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: Checkpoint inhibitors; Immune related adverse events; Cholestasis; Severe ductopenia; Vanishing bile duct syndrome
Online: 20 January 2022 (11:07:21 CET)
Tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI) significantly improve the outcomes of patients with advanced clear cell renal cell carcinoma (ccRCC), but high-grade toxicities can occur, particularly during combination therapy. Herein, we report a patient with advanced metastatic ccRCC, who developed grade 4 cholestasis during combined therapy with nivolumab and cabozantinib. After the exclusion of common disorders associated with choles-tasis and a failure of corticosteroids (CS), a liver biopsy was performed that demonstrated severe ductopenia. Consequently, a diagnosis of vanishing bile duct syndrome related to TKI and ICI administration was made, resulting in CS discontinuation and ursodeoxycholic acid administra-tion. After a 7-months follow-up, liver tests had returned to normal values. Immunological studies revealed that our patient had developed robust T-cells and macrophages infiltrates in his lung metastasis, as well as in skin and liver tissues at the onset of toxicities. At the same time, peripheral blood immunophenotyping revealed significant changes in T-cell subsets suggesting their potential role in the pathophysiology of the disease.
REVIEW | doi:10.20944/preprints202006.0216.v2
Subject: Life Sciences, Virology Keywords: SARS-coronavirus; Severe Acute Respiratory Syndrome; COVID-19; Stool; Urine; Wastewater; Wastewater-based epidemiology
Online: 18 June 2020 (09:29:00 CEST)
The COVID-19 pandemic has revealed many knowledge gaps with implications toward the speed and nature of our response to contain, assess and mitigate risk. The routine discharge of treated and untreated wastewater into rivers and coastal waters has placed SARS-CoV-2 viability in wastewater at the centre of an emerging hazard and potential risk to water industry workers and the public who come into contact with sewage-impacted water. Here we provide a review of the Severe Acute Respiratory Syndrome coronavirus primary literature that presents the evidence base pertaining to the key questions of whether the SARS-CoV-1 and SARS-CoV-2 is shed in stool and urine, is recoverable, and infectious in wastewater. We discuss the challenges posed by the current literature base and the extent to which the current evidence is fit for the purpose of informing robust human and environmental risk assessments.
Subject: Keywords: COVID-19; SARS-CoV-2; coronavirus; severe acute respiratory syndrome coronavirus; meta-analysis
Online: 16 March 2020 (01:06:04 CET)
Introduction: The 2019 novel coronavirus (COVID-19) is very contagious, and can be transmitted to other people by droplet, aerosol, sneezing, infected surface, and cough. There is no vaccine or effective treatment at this time. Therefore, the prevention of COVID-19 and the rapid diagnosis of infected patients is crucial. Method: We searched all relevant literature published up to February 28, 2020, from Embase, Scopus, PubMed, Web of Science, and the Cochrane library to collect the studies that reported clinical and laboratory characteristics of COVID-19 infected patients. The study quality was assessed with the Critical Appraisal Checklist. Depending on the heterogeneity test, we used either random or fixed-effect models to analyze the appropriateness of the pooled results. Result: Twenty studies were included in the meta-analysis, including a total of 52,251 patients with confirmed COVID-19 infection. 69.5% (95% CI 54.5-81, p < 0.001) of patients had a history of recent travel to Wuhan, contact with people from Wuhan, or lived in Wuhan. The most common symptoms among COVID-19 infected patients were fever 85.6 % (95% CI 73 -93, p < 0.001), and cough 63 % (95% CI 55.5-70, p < 0.001), respectively. The laboratory analysis showed that thrombocytosis was present in 91% (95% CI 81-98, p < 0.001) CRP was elevated in 81% (95% CI 65-91, p < 0.001), and lymphopenia in 62.5% of cases (95% CI 42-79, p < 0.001). The most common radiographic signs were bilateral involvement in 76.8% (95% CI 62.5-87, p < 0.001) and consolidation in 75.5% (95% CI 50.5-91, p < 0.001) of patients. Most patients (85.4%) were hospitalized, 20.6% of patients were admitted to the ICU in critical condition, and the mortality rate was 5.6%. Conclusions: Fever and cough are the most common symptoms of COVID-19 infection in the literature published to date. Thombocytosis, lymphopenia, and increased CRP were common lab findings although most patients included in the overall analysis did not have laboratory values reported. The most common radiographic sign was bilateral involvement in and consolidation. Among Chinese patients with COVID-19, rates of hospitalization, critical condition, and hospitalization were high in this study, but these findings may be biased by reporting only confirmed cases.
ARTICLE | doi:10.20944/preprints201812.0338.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: severe aortic stenosis; longitudinal axis strain; late gadolinium enhancement; cardiac magnetic resonance imaging
Online: 28 December 2018 (07:12:57 CET)
To analyze the predictive ability and incremental value of left ventricular longitudinal axis strain (LAS) and late gadolinium enhancement (LGE) using standard cardiovascular magnetic resonance (CMR) imaging for the diagnosis and prognosis of severe aortic stenosis (AS) in patients with an indication for aortic valve replacement. We conducted a prospective study on 128 patients with severe AS and 52 volunteers. The evaluation protocol included standard biochemistry tests, novel biomarkers of myocardial fibrosis, 12-lead electrocardiograms and 24-hour Holter, the 6-minute walk test and extensive echocardiographic and CMR imaging studies. Outcomes were defined as the composite of major cardiovascular events (MACEs). Among AS patients, most (n = 17, 77.2%) of those who exhibited LGE at CMR imaging had MACEs during follow-up. Kaplan-Meier curves for event-free survival showed a significantly higher rate of MACEs in patients with LGE (p < 0.01) and decreased LAS (p < 0.001). In Cox regression analysis, only reduced LAS [hazard ratio 1.33, 95%CI (1.01 to 1.74), p < 0.01] and the presence of LGE [hazard ratio 11.3, 95%CI (1.82 to 70.0), p < 0.01] were independent predictors for MACEs. The predictive value increased if both LGE and reduced LAS were added to LVEF. None of the biomarkers of increased collagen turnover exhibited any predictive value for MACEs. LAS by CMR is an independent predictor of outcomes in patients with AS and provides incremental value beyond the assessment of LVEF and the presence of LGE.
ARTICLE | doi:10.20944/preprints201712.0009.v1
Subject: Materials Science, Metallurgy Keywords: Cu-Cr-Zr alloy; grain refinement; severe plastic deformation; triple junctions; grain refinement kinetics
Online: 1 December 2017 (16:05:29 CET)
The microstructure evolution and grain refinement kinetics of a solution treated Cu – 0.1Cr – 0.06Zr alloy during equal channel angular pressing (ECAP) at a temperature of 673 K via route BC were investigated. The microstructure change during plastic deformation was accompanied by the microband formation and an increase in the misorienations of strain-induced subboundaries. The refinement of initial coarse grains was considered as a result of continuous dynamic recrystallization. The dynamic recrystallization kinetics was discussed in terms of grain/subgrain boundary triple junction evolution. The strain dependence of the triple junctions of high-angle boundaries can be expressed by a modified Johnson-Mehl-Avrami-Kolmogorov relationship with a strain exponent of about 1.49. Severe plastic deformation by ECAP led to substantial strengthening of the Cu-0.1Cr-0.06Zr alloy. The yield strength increased from 60 MPa in the initial state to 445 MPa after the total strain of 12.
ARTICLE | doi:10.20944/preprints202202.0333.v1
Subject: Medicine & Pharmacology, Allergology Keywords: antibody; BNT162b2; coronavirus disease 2019; severe acute respiratory syndrome coronavirus 2; vaccine hesitancy; vaccine booster
Online: 25 February 2022 (10:01:23 CET)
This was a retrospective cohort study, which aimed to investigate the factors associated with hesitancy to receive the third dose of coronavirus disease 2019 (COVID-19) vaccine. A paper-based questionnaire survey was administered to all participants. Accordingly, the study included participants who provided answer in the questionnaire whether they have an intent to receive the third dose of vaccine. Data on sex, age, area of residence, adverse reactions after the second vaccination, whether the third vaccination was desired, and reasons to accept or hesitate booster vaccination were retrieved. Among the 2439 participants with mean (±SD) age of 52.6±18.9 years, and median IgG-S antibody titer of 324.9 (AU/mL), 97.9% of participants indicated their intent to accept a third vaccination dose. The logistic regression revealed that younger age (OR=0.98; 95% CI: 0.96-1.00) and higher antibody level (OR=2.52; 95% CI: 1.27-4.99) are positively associated with the third vaccine hesitancy. The efficacy of the COVID-19 vaccine and concerns about adverse reactions had significant impact on the third vaccination behavior. A rapid increase in the booster dose rate is needed to control the pandemic, and specific approaches should be taken in these groups that are likely to hesitate the third vaccine, subsequently increasing booster contact rate.
REVIEW | doi:10.20944/preprints202105.0311.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Angiotensin converting enzyme 2; breast feeding; drug therapy; pregnancy; severe acute respiratory syndrome coronavirus 2
Online: 13 May 2021 (15:26:34 CEST)
The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become the chief concern of the international community in almost no time. As of May 9th, 2021, more than 150 million cases and 3.2 million deaths have been recorded. Considering the early struggle in treating COVID-19 patients, the researchers and clinicians have decided to try the previously available drugs according to their mechanisms of action. Hence, many antivirals, antibiotics, antiparasitics, and antipyretics have been proposed. Pregnant women, fetuses, and infants are known high-risk populations that are threatened during disease outbreaks. Therefore, this article reviews the safety of potential drugs for COVID-19 patients during pregnancy and breastfeeding.
REVIEW | doi:10.20944/preprints201807.0050.v1
Subject: Materials Science, General Materials Science Keywords: severe plastic deformation (SPD); mode deformation; simple shear and pure shear; structure modification; SPD techniques
Online: 3 July 2018 (13:10:23 CEST)
In this review, severe plastic deformation (SPD) is considered as a materials processing technology. The deformation mode is the principal characteristic differentiating SPD from common forming operations. For large plastic strains, deformation mode depends on the distribution of strain rates between continuum slip lines and can be varied from pure shear to simple shear. A scalar, invariant and dimensionless coefficient of deformation mode is introduced as a normalized speed of rigid rotation. On this basis, simple shear provides the optimum mode for structure modification and grain refinement whereas pure shear is "ideal" for forming operations. Special experiments and SPD practice confirm this conclusion. Various techniques of SPD are classified and described in accordance with simple shear realization or approximation. It is shown that correct analyses of the processing mechanics and technological parameters are essential for comparison of SPD techniques and the development of effective industrial technologies.
ARTICLE | doi:10.20944/preprints202010.0380.v1
Subject: Earth Sciences, Other Keywords: APR1400; COM3D; Containment Integrity; Hydrogen Flame Acceleration; Multi-Dimensional Hydrogen Analysis System; Overpressure; PAR; Severe Accident
Online: 19 October 2020 (13:20:32 CEST)
Korea Atomic Energy Research Institute (KAERI) established a multi-dimensional hydrogen analysis system to evaluate a hydrogen release, distribution, and combustion in the containment of a nuclear power plant using MAAP, GASFLOW, and COM3D. KAERI developed the COM3D analysis methodology on the basis of the COM3D validation results against the experiments of ENACCEF and THAI. The proposed analysis methodology accurately predicts the peak overpressure with an error range of approximately ±10% using the Kawanabe turbulent flame speed model. KAERI performed a hydrogen flame acceleration analysis using the multi-dimensional hydrogen analysis system for a severe accident initiated by a station blackout (SBO) under the assumption of 100% metal-water reaction in the reactor pressure vessel for evaluating an overpressure buildup in the Advanced Power Reactor 1400 MWe (APR1400). The COM3D calculation results using the established analysis methodology showed that the calculated peak pressure in the containment was much lower than the fracture pressure of the APR1400 containment. This calculation result may have resulted from a large air volume of the containment, a reduced hydrogen concentration owing to passive auto-catalytic recombiners installed in the containment, and a lot of stem presence during the hydrogen flame acceleration in the containment. Therefore, we can know that the current design of the APR1400 containment maintains its integrity when the flame acceleration occurs during the severe accident initiated by the SBO accident.
ARTICLE | doi:10.20944/preprints201809.0540.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: Modified FOLFIRINOX; Severe neutropenia; Overall survival; Overall response rate; Time to treatment failure; Advanced pancreatic cancer
Online: 27 September 2018 (10:12:08 CEST)
Modified FOLFIRINOX is effective for advanced pancreatic cancer but frequently causes severe neutropenia. The present study was designed to investigate the influence of severe neutropenia on clinical outcomes in advanced pancreatic cancer patients receiving modified FOLFIRINOX. Fifty-one advanced pancreatic cancer patients who received modified FOLFIRINOX during January 2014 and May 2018 were subjects of the present study. Adverse events, including neutropenia, were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. Median overall survival (OS) was determined as the primary endpoint, while median time to treatment failure (TTF), overall response rate (ORR), and the incidence of other adverse events were measured as secondary endpoints. Severe neutropenia (grade≥3) occurred in 39 patients (76.4%), in which high level of total bilirubin (>0.6mg/dL) was a significant risk as assessed by a multivariate logistic regression analysis. Median duration of OS was significantly longer in patients with severe neutropenia than in those without it (15.2 months versus 7.2 months, P=0.032). Moreover, there was a significant correlation between OS and the grade of neutropenia (R=0.306, P=0.029). ORR tended to be higher, though not significantly, in patients with severe neutropenia. In contrast, the incidence rates of other adverse events were not different between the two groups. Severe neutropenia is an independent predictor of prognosis in advanced pancreatic cancer patients received modified FOLFIRNOX therapy.
HYPOTHESIS | doi:10.20944/preprints202004.0317.v2
Subject: Keywords: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2); COVID19; Middle East Respiratory Syndrome Coronavirus; bioaerosol; aerosol
Online: 30 April 2020 (05:30:30 CEST)
A short review of the important studies was conducted to evaluate the potential of aerosol transmission of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The minimum size of droplets potentially carrying the SARS-CoV-2 was newly estimated and discussed in this review.
REVIEW | doi:10.20944/preprints202004.0469.v1
Subject: Biology, Other Keywords: severe acute respiratory syndrome coronavirus-2; COVID-2019; epidemiology; pathobiology; clinical profile; phyloanalysis; artificial intelligence; diagnosis; vaccines; therapeutics
Online: 26 April 2020 (08:15:23 CEST)
The technology-driven world of the 21st century is currently confronted with a major threat to humankind in the form of the coronavirus disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). As of April 22, 2020, COVID-19 has claimed 169, 006 human lives and had spread to over 200 countries with more than 2,471,136 confirmed cases. The perpetually increasing figures associated with COVID-19 are disrupting the social and economic systems globally. The losses are unmatched and significantly higher compared to those from previously encountered pathogenic infections. Previously, two CoVs (SARS-CoV and Middle East respiratory syndrome-CoV) affected the human population in 2002 and 2012 in China and Saudi Arabia, respectively. Based on genomic similarities, animal-origin CoVs, primarily those infecting bats, civet cats, and pangolins, were presumed to be the source of emerging human CoVs, including the SARS-CoV-2. The cohesive approach amongst virologists, bioinformaticians, big data analysts, epidemiologists, and public health researchers across the globe has delivered high-end viral diagnostics. Similarly, vaccines and therapeutics against COVID-19 are currently in the pipeline for clinical trials. The rapidly evolving and popular technology of artificial intelligence played a major role in confirming and countering the COVID-19 pandemic using digital technologies and mathematical algorithms. In this review, we discuss the noteworthy advancements in the mitigation of the COVID-19 pandemic, focusing on the etiological viral agent, comparative genomic analysis, population susceptibility, disease epidemiology, animal reservoirs, laboratory animal models, disease transmission, diagnosis using artificial intelligence interventions, therapeutics and vaccines, and disease mitigation measures to combat disease dissemination.
ARTICLE | doi:10.20944/preprints202208.0392.v1
Subject: Life Sciences, Virology Keywords: Severe Acute Respiratory Syndrome-CoV-2 (SARS-CoV2), COVID-19, molecular diagnostics, real-time polymerase chain reaction (RT-qPCR)
Online: 23 August 2022 (03:55:44 CEST)
Background: Coronavirus disease (COVID-19) is an infectious disease caused by the SARS-CoV-2. In Colombia, many commercial methods are now available to perform the RT-qPCR assays, and the laboratories must evaluate its diagnostic accuracy to ensure reliable results to suspected COVID-19 patients. The purpose of the study was to compare four commercial RT-qPCR assays for detection of SARS-CoV2 virus, from nasopharyngeal swab samples referred to Laboratorio Carvajal IPS, SAS of Tunja, Boyacá - Colombia. Methods: This prospective study was conducted on 152 samples of respiratory tract samples (Nasopharyngeal Swab) from patients with suspected SARS-CoV-2 infection. Diagnostic accuracy of GeneFinderTM COVID-19 Plus RealAmp (In Vitro diagnostic), One-Step Real-Time RT-PCR (Vitro Master diagnostica), Berlin modified protocol and gold standard Berlin protocol (Berlin Charite Probe One-Step RT-qPCR Kit, New England Biolabs) as reference was assessed. Operational characteristics were estimated in terms of sensitivity, specificity, agreement, and predictive values. Results: Using Berlin Charite Probe One-Step RT-qPCR Kit as reference, the sensitivity/specificity for the diagnostic tests were found to be GeneFinderTM COVID-19 Plus RealAmp Kit 100%/92.7%, One-Step Real-Time RT-PCR, One-Step Real-Time RT-PCR 92.75%/67.47%, and Berlin modified protocol 100%/96.39%. The results of four commercially available methods were found to be consistent with those obtained from Berlin Modified protocol analysis for % of the samples and showed good agreement (κ= 0.96). Concordant SARS-CoV2 negative and positive RT-qPCR results were reported for xxx and xxx samples, respectively. Summarize something about the Ct. Conclusion: Our data demonstrate that all commercially available methods are rapid and reliable for the identification of SARS-CoV-2 virus associated with COVID-19. One-Step RT-qPCR Kit and GeneFinderTM COVID-19 Plus RealAmp assay show optimal sensitivity compared with Belin modified protocol. In addition, there is no significant correlation between xxxxx
Subject: Keywords: Pangolin; Intrinsic; Disorder; Protein; Nucleocapsid; Virulence; Shell; Covid; Coronavirus; Vaccine; Immune; Antibody; Shell; Nucleoprotein; Matrix; Attenuate; Severe Acute Respiratory
Online: 4 May 2021 (16:24:51 CEST)
SARS-CoV-2 was empirically and computationally found to be of a specific but peculiar evolution. Shell disorder models found that the outer shell (M protein) of SARS-CoV-2 to be among the hardest in its CoV family. The hard outer shell (low M percentage of disorder (PID)) is likely to be related to the SARS-CoV-2 resistance to the antimicrobial enzymes in saliva and mucus, and be responsible for the high-level of viral shedding which has been observed clinically. Experimental studies have also shown that SARS-CoV-2 is more resilient in the environment than many other CoVs, including SARS-CoV-1. Another aspect of the shell disorder models predicts that SARS-CoV-1 is more virulent than SARS-CoV-2 because of higher inner shell disorder (N PID) that helps SARS-CoV-1 replicate faster in vital organs despite being of lesser viral loads in the saliva and mucus, unlike SARS-CoV-2. This has been reaffirmed experimentally, where higher levels (50 folds) of infectious particles were detected in the SARS-CoV-1 samples in comparison with those of SARS-CoV-2. The hard outer shell of SARS-CoV-2 has been found to be associated with burrowing animals, particularly pangolins, which are often in contact with buried feces. For these reasons, the M protein is highly conserved among close relatives of SARS-CoV-2. The phylogenetic tree using M, unlike the genome-wide one, shows that pangolin-CoVs are more closely related to SARS-CoV-2 than bat-RaTG13. Previous phylogenetic studies may have been confused by recombinations that are usually poorly handled. According to the shell disorder models based on the N PID, an attenuated COVID-19 strain is likely to have entered humans via pangolins in 2017 or before, which provides the virus enough time to adapt to humans. This could explain why the SARS-CoV-2 S protein is highly adapted to the human ACE-2. The specific but peculiar evolution has a wide range of clinical, immunological, and epidemiological implications.
REVIEW | doi:10.20944/preprints202009.0076.v1
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: severe acute respiratory syndrome coronavirus 2; SARS-CoV-2; coronavirus disease 2019; COVID-19; viral infection; virus-host interaction
Online: 4 September 2020 (03:19:43 CEST)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing pandemic of coronavirus disease 2019 (COVID-19). The worldwide transmission of COVID-19 from human to human is spreading like wildfire, affecting almost every country in the world. In the past 100 years, the globe did not face microbial pandemic similar in scale to COVID-19. Taken together, both previous outbreaks of other members of the coronavirus family (SARS-CoV and MERS-CoV) did not produce even 1% of the global harm already inflicted by COVID-19. There are also four other CoVs capable of infecting humans (HCoVs), which circulate continuously in the human population, but their phenotypes are generally mild, and these HCoVs received relatively little attention. These dramatic differences between infection with HCoVs, SARS-CoV, MERS-CoV, and SARS-CoV-2 raise many questions, such as: Why is COVID-19 transmitted so quickly? Is it due to the some specific features of the viral structure? Are there some specific human (host) factors? Are there some environmental factors? The aim of this review is to collect and concisely summaries the possible and logic answers to these questions.
ARTICLE | doi:10.20944/preprints202004.0171.v2
Subject: Life Sciences, Virology Keywords: protein functional domains; short linear motifs; coronaviruses; COVID-19; severe acute respiratory syndrome-related coronavirus; 2019-nCoV; virus outbreak
Online: 16 May 2020 (18:54:17 CEST)
Although phylogenetic analysis shows coronaviruses (CoV) share similar genome sequences, CoVs encode different number of proteins (5 to 14), which has implication on viral pathogenicity and infection. Here, we aimed to identify (in-silico) the similarities between different members of coronavirus family. The analysis included 50 coronavirus proteomes, including SARS-CoV-2 (COVID-19), to find the variation of the number of protein functional motifs and domain in each coronavirus. For this role, we used the experimentally validated domain (motif) that known to be crucial for viral infection. Although human CoVs are classified within one genus, we found variations among them. SARS-CoV-1, SARS-CoV-2 and MERS-CoV encode different type of domains, which has implications on the molecular interactions triggered by each virus within human cells. Secondly, we used functional motifs to reconstruct the potential molecular pathways or interactions triggered by SARS-CoV-2 proteins within human cell.
Subject: Life Sciences, Virology Keywords: SARS-CoV-2; COVID-19; novel severe acute respiratory syndrome coronavirus 2; ancestral reconstruction; clonality; source of entry; dispersal routes
Online: 28 June 2020 (09:21:49 CEST)
The coronavirus disease 2019 (COVID-19) was officially declared a pandemic on the 11th March 2020. It is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), impacting the lower respiratory tract. International travel to Australia during the early stages of the pandemic prior to border closure provided avenues for this virus to spread into Australia. There is little understanding of the clonality of SARS-CoV-2 isolates in Australia, and where they originated. This study aimed to investigate the clonality and ancestral sources of SARS-CoV-2 isolates in Australia using in silico methods. We retrieved 1,346 complete genomes from Australia along with 153 genomes from other countries from the NCBI nucleotide database and Global Initiative On Sharing All Influenza Data (GISAID). We then constructed a representative population of 270 sequences for downstream phylogenetic analysis and ancestral area reconstruction. Overall, two major clusters, one stemming from Europe and another from Asia, especially East Asia, were observed, implying at least two major transmission events with subsequent clades confirming the multiclonality of Australian isolates. We also identified three potential dissemination routes of SARS-CoV-2 into Australia. This study supports the hypothesis of multiple clonality and dispersals of SARS-CoV-2 isolates into Australia.
Subject: Biology, Anatomy & Morphology Keywords: COVID-19; Severe acute respiratory syndrome (SARS); SAR-CoV-2; flow cytometry; flow virometry; viral particles; herpes simplex virus; HSV; nanoparticles
Online: 12 May 2020 (07:45:53 CEST)
The coronavirus disease caused by SARS-CoV-2 (known as COVID 19) is highly contagious and has spread rapidly over 200 countries over last three months. WHO suggested urgent escalation in testing, isolation and contact tracing, as the "backbone" of managing the pandemic. Globally, the detection of SARS-CoV-2 in patients are done by RT-PCR and blood antibody-based testing. In addition to the existing processes, flow-cytometry could be used as a high-throughput and efficient diagnostic method for detection of COVID 19. The suspected COVID 19 samples can be analyzed using ‘Indirect flow cytometry’, with the specific primary antibody and fluorescent tagged secondary antibodies. The fluorescence signal can distinguish the infected v/s non-infected samples. In the present article, we have summarized the applications of Flow virometry to study various viruses and have proposed possible application in the detection of COVID 19.
ARTICLE | doi:10.20944/preprints202102.0059.v1
Subject: Medicine & Pharmacology, Allergology Keywords: COVID-19; Critical Illness; Hospital Mortality; Intensive Care Units; Outcome Assessment, Health Care; Prognosis; Risk Adjustment; Severe acute respiratory syndrome coronavirus 2
Online: 1 February 2021 (15:51:34 CET)
Objectives To develop and validate a prediction model for 28-day in-hospital mortality among adult patients critically ill with COVID-19 in the UK. Design Observational cohort study. Setting 287 adult critical care units in England, Wales and Northern Ireland, of which 260 admitted at least one eligible patient. Participants 10,933 patients with confirmed COVID-19 of whom 10,401 were eligible (excluding 532 patients with a duration of critical care less than 24 hours and 1 patient with unknown 28-day outcome): 8,666 development (March-April 2020) and 1,735 temporal validation (May-August 2020). Main outcome measures 28-day in-hospital mortality from start of critical care. Results Two models were developed using 14 patient level predictors selected from 30 candidate predictors, with and without adjustment for calendar time. In the temporal validation data, the model discrimination was maintained (c index 0.78) but calibration was poor, particularly for the model not adjusted for calendar time (ratio of observed to predicted mortality 0.74 versus 0.88 for the model adjusted for calendar time). Conclusions We developed and validated a prediction model for 28-day in-hospital mortality for patients critically ill with COVID-19. Although absolute predictions were inaccurate due to changing outcomes, the models will support risk-adjustment in analyses and monitoring changes in risk-adjusted outcome over time.
BRIEF REPORT | doi:10.20944/preprints202003.0338.v3
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: Severe Acute Respiratory Syndrome Coronavirus-2; (soluble) ACE2; eosinophil; asthma; IL-10; Lung fibrosis; hypercapnic acidosis; hypoxia; infarction; hypertension; cardiac dysfunction; respiratory distress; coagulopathy; Angiotensin; renin; Ang (1-7); Ang (1-9); Mas receptor; AT2 receptor
Online: 6 May 2020 (04:40:25 CEST)
The article describes the rational for inhibition of the angiotensin-converting enzyme 2 (ACE2) pathways as specific targets in patients infected by SARS-CoV-2 in order to prevent the establishment of positive feedback loops triggered by COVID-19 in some predisposed subjects. Making use of a large quantity of published reports in which human/rodent ACE2 pathway inhibitors were administered in vivo, it is hypothesized a possible therapeutic pharmacological intervention through an inhibition strategy of the zinc metalloprotease ACE2 and its downstream pathway for SARS-CoV-2 patients. Of even more interest, metal (zinc) chelators and renin inhibitors (both FDA approved drugs) may also work alone or in combination in inhibiting the positive feedback loops, initially triggered by COVID-19 and subsequently sustained by hypoxia independently on viral trigger, when both arms of renin-angiotensin system (ACE2 and ACE) are upregulated, leading to critical, advanced and untreatable stages of the disease.
ARTICLE | doi:10.20944/preprints201804.0278.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: monocyte chemoattractant protein-1; MCP-1; C-C motif chemokine ligand 2; CCL2; childhood asthma; bronchial asthma; severe asthma; cystic fibrosis; chronic obstructive pulmonary disease
Online: 23 April 2018 (09:00:00 CEST)
C-C motif chemokine ligand 2 (CCL2), also called monocyte chemoattractant protein-1 (MCP-1) is a key β-chemokine involved in the migration of monocytes and macrophages, playing a significant role in the inflammatory responses in the airways. We aimed to assess the serum levels of MCP-1/CCL2 in a pilot cross-sectional study of Bulgarian children with bronchial asthma (BA) and cystic fibrosis (CF). Forty-two children were recruited to the study as follows: twenty with BA, twelve with CF and ten healthy children. Serum MCP-1/CCL2 levels were measured using ELISA. We found higher serum level of MCP-1/CCL2 in children with BA (191.09±64.96 pg/ml) and CF (258.51±76.45 pg/ml) compared to healthy children (70.30±64.30 pg/ml, p=0.022, and p=0.068, respectively). Younger patients with BA had higher levels of MCP-1/CCL2, as well as children with CF, with levels decreasing gradually with age. We observed also higher levels of MCP-1/CCL2 in children with moderate to severe BA compared to mild BA. We documented the significantly higher level of MCP-1/CCL2 in children with these chronic pulmonary diseases than in healthy controls, which suggesting that investigation of serum MCP-1/CCL2 levels could turn out to be beneficial for the severity of the disease.
HYPOTHESIS | doi:10.20944/preprints202004.0153.v1
Subject: Life Sciences, Other Keywords: Severe acute respiratory syndrome coronavirus 2; 2019-nCoV; COVID-19; angiotensin converting enzyme 2; Receptor; Live Attenuated Oral Vaccine; Intestine; proximal and distal enterocytes; herd immunity
Online: 9 April 2020 (13:10:50 CEST)
Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2/2019-nCoV) infection is an emerging pandemic. The virus binds to angiotensin converting enzyme 2 (ACE2) and TMPRSS2 which are abundantly expressed on various human cells including lung epithelial cells and intestinal cells and the virus can infect these cells. Currently no specific treatments or vaccines are available for this disease. A per oral live attenuated vaccine can be beneficial in SARS-Cov-2 infection because the attenuated virus initially infects the gut, stimulates the mucosa associated immune system sparing the respiratory system during the initial immune response. The live virus can also spread in the community boosting herd immunity.
ARTICLE | doi:10.20944/preprints202209.0291.v1
Subject: Life Sciences, Virology Keywords: COVID-19; Multidimensional Analysis; HCA; Hierarchical cluster analysis; regression analysis; mild; moderate; severe; Age; Score index of the chest X-ray; percentage and quantity of neutrophils; Albumin; C reactive protein; ratio of Lymphocytes
Online: 20 September 2022 (04:50:36 CEST)
INTRODUCTION: The purpose of the study was to determine (a) the overall preclinical character; (b) the cumulative cutoff values and the risk ratio, and (c) the factors associated with severity by a unidimensional and multidimensional analysis on 2173 Sars-Cov2 patients. METHODS: The machine learning study population consisted of 2173 patients (1587 mild and non symptoms patients, 377 moderate patients, 209 severe patients). The status of the patients was recorded from September 2021 to March 2022. RESULTS: The Covid19 Severity directly links with a significant correlation to Age, Score index of the chest X-ray, percentage and quantity of neutrophils, Albumin, C reactive protein, and ratio of Lymphocytes. Their important cut off values (from regression analysis) respectively are: 77.56 years old (the mild-moderate group), 5.53 (the mild-moderate group) and 10.51 (the moderate-severe group), 84.80% (the mild-moderate group) and 87.74%(the moderate-severe group), 11.77G/L (the moderate-severe group), 29.73g/L (the moderate-severe group), 7.46mg/dL (the mild-moderate group), 6.32% (the moderate-severe group). Their significant (p<0.0001) R score correlation with the severity of Covid19, are: 0.44, 0.52 and 0.52, 0.33 and 0.44, 0.42, -0.43, 0.40, -0.41. Their significant risk ratio (p<0.00001) from the meta-analysis, respectively are: 4.19 [3.58-4.95], 3.29 [2.76-3.92] and 3.03 [2.4023;3.8314], 3.18 [2.73-3.70] and 3.32 [2.6480;4.1529], 3.15 [2.6153;3.8025], 3.4[2.91-3.97], 0.46 [0.3650;0.5752] (p<0.00001), 0.34 [0.2743;0.4210]. The pair ALT – Leucocytes and Transferrin – Anion Chloride get the most important correlation shift. ALT – Leucocytes show the important negative link (R=-1, p<0.00001) in the mild group to the significant positive correlation in the moderate group (R=1, p<0.00001). Transferrin–anion Chloride has an important positive association (R=1, p<0.00001) in the mild group with a significant negative correlation in the moderate group (R=-0.59, p<0.00001). The network map and HCA show that in the mild-moderate group, the closest neighbors with the Covid19 severity are ferritins, Age. Then there is C-reactive protein, SI of X-ray, Albumin, and Lactate dehydrogenase, which are the next close neighbors of these three factors. In the moderate-severe group, the closest neighbors with the Covid19 severity are Ferritin, Fibrinogen, Albumin, the quantity of Lymphocytes, SI of X-ray, white blood cells count, Lactate dehydrogenase, and quantity of neutrophils. CONCLUSIONS: Complete multidimensional study in 2173 Covid19 patients in Vietnam shows the whole picture of all the preclinical factors, which may become the clinical reference marker for surveillance and diagnostic management
ARTICLE | doi:10.20944/preprints202209.0102.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: acute malnutrition; combined protocol; community-based management of acute malnutrition; ef-fectiveness; Mali; mid-upper-arm circumference; moderate acute malnutrition; ready-to-use ther-apeutic food; treatment; severe acute malnutrition; simplified protocol; wasting
Online: 7 September 2022 (05:21:16 CEST)
The simplified, combined protocol admits children with a mid-upper-arm circumference (MUAC) of <125 mm or edema to malnutrition treatment with ready-to-use therapeutic food (RUTF) prescribing 2 daily RUTF sachets to children with MUAC <115 mm or edema and 1 daily sachet to those with MUAC ≥115 mm but <125 mm. This treatment has previously been shown to result in non-inferior programmatic outcomes compared to standard treatment. We aimed at observing its effectiveness in a routine setting at scale, including via delivery by community health workers (CHW). A total of 27 601 children were admitted to the simplified, combined treatment. Treatment resulted in 96% overall recovery with a mean LOS of 40 days and a mean RUTF consumption of 63 sachets per child treated. Among children admitted with MUAC <115 mm or edema 94% recovered with a mean LOS of 55 days and consuming an average of 97 RUTF sachets. Recovery in all sub-groups studied exceeded 90%.Treatment by CHWs resulted in similar (96%) recovery as treatment by formal health care workers (96%). The simplified, combined protocol results in high recovery and low RUTF consumption per child treated, and can safely be adopted by CHWs to provide treatment in the community-level.
REVIEW | doi:10.20944/preprints202106.0377.v2
Subject: Life Sciences, Biochemistry Keywords: aa = amino acids; ACE-2 = receptor angiotensin-converting enzyme 2; cDNA = complementary DNA; mRNA = messenger RNA; orf = open reading frame; RBD = receptor binding protein; S-protein = Spike protein; SARS-CoV-2 = severe respiratory syndrome coronavirus 2; Vaccines.
Online: 22 June 2021 (11:53:34 CEST)
The SARS (severe acute respiratory syndrome)-CoV (Coronavirus)-2 S(spike)-protein mRNA/cDNA currently being used as vaccines are antigenic but not antigens against SARS-CoV-2, that causes COVID (Coronavirus Disease) -19. Furthermore, the mRNA and cDNA antigenic vaccines also have potentials for homologous as well as heterologous recombination, primarily into the somatic cell DNA of the vaccine recipients. On the contrary, a SARS-CoV-2 RBD-protein antigen, a part of the S-protein, will directly stimulate antibody production against SARS-CoV-2. Hence, a vaccine composed of SARS-CoV-2 RBD-protein as a safer, fast acting, and effective vaccine against SARS-CoV-2 and thus against COVID-19. This is also useful for some immune compromised individuals.