ARTICLE | doi:10.20944/preprints202209.0289.v1
Subject: Medicine And Pharmacology, Clinical Medicine Keywords: chronic fatigue syndrome; post-COVID syndrome; postural orthostatic tachycardia; microcirculation; immune system
Online: 20 September 2022 (03:37:00 CEST)
A Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic disease of unknown aetiology under growing interest now in view of the increasingly recognized post-COVID syndrome as a new entity with similar clinical presentation. We performed the first cross-sectional study of ME/CFS in community population in Russia and then described and compared some clinical and pathophysiological characteristics of ME/CFS and post-COVID syndrome as neuroimmune disorders. Of the cohort of 76 individuals who suggested themselves suffering from ME/CFS 56 subsequently were confirmed as having CFS/ME according to ≥1 of the 4 most commonly used case definition. Of the cohort of 14 individuals with post-COVID-19 syndrome 14 met diagnostic criteria for ME/CFS. The prevalence of clinically expressed and subclinical anxiety and depression in ME / CFS and post-COVID ME/CFS did not differ significantly from that in healthy individuals. Severity of anxiety / depressive symptoms did not correlate with the severity of fatigue neigther in ME / CFS nor in post-COVID ME/CFS, but the positive correlation was found between the severity of fatigue and 20 other symptoms of ME / CFS related to the domains of “post-exertional exhaustion”, “immune dysfunction”, “sleep disturbances”, "dysfunction of the autonomic nervous system", "neurological sensory / motor disorders" and "pain syndromes". Immunological abnormalities were identified in 12/12 patients with ME / CFS according to the results of laboratory testing. The prevalence of postural orthostatic tachycardia assessed by the active standing test was 37.5% in ME / CFS and 75.0% in post-COVID ME/CFS (the latter was higher than in healthy controls, p = 0.02) There was a more pronounced increase in heart rate starting from the 6th minute of the test in post-COVID ME/CFS compared with the control group. Assessment of the functional characteristics of microcirculation by laser doppler flowmetry revealed obvious and very similar changes in ME/CFS and post-COVID ME/CFS compared to the healthy controls. The identified pattern corresponded to the hyperemic form of microcirculation disorders, usually observed in acute inflammatory processes or in deficiency of systemic vasoconstriction influences.
ARTICLE | doi:10.20944/preprints202205.0216.v2
Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Bioimpedance; COVID-19; E-health; Health Care Personnel; Pathophysiology; Post-COVID syndrome; Rheography
Online: 23 May 2022 (05:26:58 CEST)
At present, there are no hardware or biochemical systems allow to assess the severity of post-COVID syndrome in vivo. The hardware of the proposed biotechnical system is based on routine transthoracic electrical impedance rheography, which makes it possible to register the frequency characteristics of the patient's bioimpedance response to controlled stress stimulation, thereby simultaneously fixing the characteristics of his productive heart, the state of the hemomicrocirculatory bed, the efficiency of the gas transport function of his blood, and also reliably assess personal reactivity and adaptive potential. Subsequent mathematical approximation of the obtained biometric data by an original neural network makes it possible to rank the results obtained and automatically generate a program of medical rehabilitation for a particular patient, depending on the severity of his post-COVID syndrome. The study results proved two reliable physiological signs confirming the presence of latent post-COVID complications: a decrease in the base impedance value for light exercise and an increase in the length of the systolic arc of the rheocardiogram.
ARTICLE | doi:10.20944/preprints202203.0277.v1
Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: Long Covid; post Covid; Post-acute COVID
Online: 21 March 2022 (08:25:20 CET)
Abstract: COVID-19 Long Haulers, an estimated 3% to 12% of people infected globally with coronavirus having latter devasting symptoms 12 weeks after the initial infection is on the rise. We conducted a collaborative study with the long covid patient organization in Greece in order to estimate the prevalence, symptoms and problems that adult long haulers experience and then propose a management plan for these patients. Symptoms were obtained from 208 patients using unstructured qualitative free text entries in an anonymized online questionnaire. The majority of respondents (68.8%) were not hospitalized and had been diagnosed more than six months ago with lingering symptoms (66,8%). Eighteen different symptoms (fatigue, tachycardia, shortness of breath, parosmia etc) were mentioned in both hospitalized and community patients. Interestingly, patients with initial mild symptoms suffer from the same persistent symptoms as those who were hospitalized. Awareness of long covid sequelae seems to be low even among medical doctors. Treatment options incorporating targeted rehabilitation programs are either not available or still excluded from the management plan of long covid patients. Since long COVID is a multi-systemic entity, we propose a holistic interventional approach using a multidisciplinary medical team in order to securely and effectively diagnose and treat these specific patients. Academic and medical community must collaborate with long covid patients’ organizations so as to provide personalized medicine.
ARTICLE | doi:10.20944/preprints202208.0227.v1
Subject: Medicine And Pharmacology, Psychiatry And Mental Health Keywords: COVID-19; depression; anxiety; post-acute COVID-19 syndrome; post-COVID
Online: 12 August 2022 (04:56:33 CEST)
Background: This study aimed to examine the course of Depression and anxiety in COVID-19 survivors with a psychiatric history compared with those without a psychiatric history. Methods: A web-based cross-sectional survey for COVID-19 survivors was conducted from July to September 2021. 6016 COVID-19 survivors, the accuracy of whose responses was determined to be assured, were included in analyses. Exposures included psychiatric history and time since COVID-19 infection, and the main outcomes and measures included severity of depression and anxiety, as assessed using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), respectively. Results: Mean severity of PHQ-9 and GAD-7 were significantly higher in participants with a psychiatric history than in those without a psychiatric history. Two-way analysis of covariance for PHQ-9 showed a significant main effect of the presence of psychiatric history and a significant interaction effect of psychiatric history × time since infection. Two-way analysis of covariance for the GAD-7 score revealed a significant main effect of the presence of psychiatric history and time since COVID-19 infection and the interaction effect of these factors. Conclusions: The course of depression and anxiety was more severe in COVID-19 survivors with a psychiatric history than in those without a psychiatric history.
ARTICLE | doi:10.20944/preprints202305.0836.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: Long covid; Post covid; Sleep disorders
Online: 11 May 2023 (09:42:22 CEST)
Objectives: To examine the long term impact of COVID-19 on sleep patterns and development of sleep disorders. Methods: Using the centralized Massachusetts General Brigham (MGB) Research Patient Data Registry (RPDR), SARS-CoV2 positive patients were surveyed about their sleep patterns before and after the viral infection. Information related to co-morbid conditions and medications were obtained through chart review. Results: Two hundred and forty five completed surverys were analysed. Average age was 53.3 ± 16.3 years, and participants were predominantly Non-Hispanic White (84.1%) and female (74.3%). Average BMI (kg/m2) was 29.9 ± 6.9, and a greater proportion was non-smokers (63.2%). After COVID-19, there was an increase in the percentage of participants reporting difficulty initiating (31 ± 46% vs. 39 ± 49%, P=0.01), and maintaining sleep (43 ± 49% vs. 57 ± 49%, P<0.001), and use of sleep aids (24 ± 43% vs. 30 ± 45% P=0.003) with an incidence rate of 24.3%, 37.4%, and 12.3% respectively. In addition, there was an increase in daytime fatigue and the need for napping (58 ± 49% vs. 36 ± 48%, P <0.0001) with an incidence of 8% and 23% respectively. The sleep symptoms persisted beyond 12 months among 28% of the participants and were predominantly seen among women. Conclusions: Infection with SARS-CoV2 has negative effects on sleep, and a significant proportion of adults experience insomnia and daytime sleepiness beyond 12 months after recovering from the initial infection.
REVIEW | doi:10.20944/preprints202305.1487.v1
Subject: Medicine And Pharmacology, Clinical Medicine Keywords: biomarkers; COVID-19; epidemiology; laboratory; long COVID; pathogenesis; post-acute sequelae of SARS-CoV-19 infection (PASC); post COVID; post-COVID syndrome (PCS)
Online: 22 May 2023 (09:41:11 CEST)
Long COVID (LC) encompasses a constellation of long-term symptoms experienced by at least 10% of people after the initial SARS-CoV-2 infection, and so far has affected about 65 million people. The etiology of LC remains unclear; however, many pathophysiological pathways may be involved, including viral persistence; chronic, low grade inflammatory response; immune dysregulation and defective immune response; reactivation of latent viruses; autoimmunity; persistent endothelial dysfunction and coagulopathy; gut dysbiosis; hormonal dysregulation, mitochondrial dysfunction; and autonomic nervous system dysfunction. There are no specific tests for the diagnosis of LC, and clinical features including laboratory findings and biomarkers may not specifically relate to LC. Therefore, it is of paramount importance to develop and validate biomarkers that can be employed for the prediction, diagnosis and prognosis of LC and its therapeutic response. Promising candidate biomarkers that are found in some patients are markers of systemic inflammation including acute phase proteins, cytokines and chemokines; biomarkers reflecting SARS-CoV-2 persistence, reactivation of herpesviruses and immune dysregulation; biomarkers of endotheliopathy, coagulation and fibrinolysis; microbiota alterations; diverse proteins and metabolites; hormonal and metabolic biomarkers; as well as cerebrospinal fluid biomarkers. At present, there are only two reviews summarizing relevant biomarkers; however, they do not cover the entire umbrella of current biomarkers or their link to etiopathogenetic mechanisms, and the diagnostic work-up in a comprehensive manner. Herein, we aim to appraise and synopsize the available evidence on the typical laboratory manifestations and candidate biomarkers of LC, their classification based on main LC symptomatology in the frame of the epidemiological and pathogenetic aspects of the syndrome, and furthermore assess limitations and challenges as well as potential implications in candidate therapeutic interventions.
REVIEW | doi:10.20944/preprints202103.0490.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Covid-19; Long Covid-19; Long Haulers Covid; Post Covid-19 Syndrome; Post-Acute Covid-19; Corona Virus; SARS-Cov-2; Novel Corona Virus 2019; Post-Acute SARS-CoV-2; PASC, Post-Acute Sequelae of COVID-19; Late Sequelae COVID-19
Online: 18 March 2021 (17:16:52 CET)
Introduction: Despite more than one year passed since the first cases of SARS-CoV-2 were reported, there is still no consensus on the definition and clinical management of post-acute-COVID-19. The condition has heterogeneously been named as Chronic COVID syndrome, Post COVID-19 Syndrome, post-acute sequela of SARS-CoV-2 (PASC), and the more familiar long COVID. Method: In order to capture all relevant published studies, we undertook a multi-step search with no language restriction. The following four-step search strategy was utilized: First, a preliminary (limited) search was conducted on January 20, 2021, in Google Scholar and PubMed to identify the appropriate keywords. Then, on January 30, 2021, we adopted a search strategy of electronic databases from Cochrane Library, PsycINFO, PubMed, Embase, Scopus, and Web of sciences, using those keywords. Then, after duplicate removal, we screened all titles, abstracts, and full texts. This resulted in 66 eligible studies. Subsequently, after a forward and backward search of their references and citations an additional 54 publications were found, resulting in a total of 120 publications that formed the basis of the present analysis. The titles, abstracts, and full-texts of non-English articles were translated using Google Translate for further evaluation. We conducted our scoping review based on the PRISMA-ScR Checklist.Results: We found only one randomized clinical trial in our search. Of the 67 original studies, 22 were cohort and 28 were cross-sectional studies totaling 74.6% of the original studies. Of the total of 120 publications, 59 (49.1%) focused on signs and symptoms, 28 (23.3%) were focused on management, and 13 (10.8%) focused on pathophysiology. Ten (9%) publications focused on imaging studies. Ninety-one percent of the original investigations came from high and upper-middle-income countries, highlighting the scarcity of reports originating from low-income and lower-middle-income countries.Conclusion: The predominant symptoms among those with the so-called “Long COVID” were: fatigue, breathlessness, arthralgia, sleep difficulties, and chest pain. Recent reports also point to the risk of long-term sequela with cutaneous, respiratory, cardiovascular, musculoskeletal, mental health, neurologic, and renal involvement in those who survive the acute phase of the illness. The ambiguity and controversies in its definition have impaired proper recognition and management of those requiring additional support following the resolution of the acute phase of this infection. This has resulted in long-standing distress for the patients and their families. Our findings highlight the need for a multidisciplinary approach, support, and rehabilitation for these patients in terms of long-term mental and physical health.
ARTICLE | doi:10.20944/preprints202205.0408.v2
Subject: Medicine And Pharmacology, Other Keywords: hesitancy; covid-19; post-covid; medical doctors; indonesia
Online: 13 September 2022 (05:13:14 CEST)
This study is a cross-sectional survey involving physicians around Indonesia aimed to explore physician hesitancy to treat COVID-19 patients after experiencing COVID-19 infection coupled with associated occupational risk factors. The questionnaire was distributed via contact information from the Indonesian Physician Association database. Out of 383 participants, 25.6% suffered from moderate symptoms of COVID-19 and 2.9% were admitted for critical care. Hesitancy to treat suspected, probable, or confirmed COVID-19 patients was found in 20.3% of physicians. A higher hesitancy rate was found in older physicians and those with less experience in treating COVID-19 patients. Specialist trainees and those who work in public hospitals were physicians with the lowest hesitancy in treating COVID-19 patients. There is a significant hesitancy in treating COVID-19 patients among physicians who have suffered from COVID-19 which calls for further action by management and policy makers.
ARTICLE | doi:10.20944/preprints202302.0145.v1
Subject: Biology And Life Sciences, Virology Keywords: COVID-19; post COVID; liver; aspartate aminotransferase; risk factors
Online: 8 February 2023 (10:47:25 CET)
The long-term laboratory aspects of the effects of COVID-19 on liver function are still not well understood. Therefore, this study aimed to evaluate the hepatic clinical-laboratory profile of patients with up to 20 months of long-term COVID-19. A total of 243 patients of both sexes aged 18 years or older hospitalised in the acute phase of COVID-19 were included in this study. Liver function analysis was performed. Changes were identified in the mean levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), and ferritin. Inflammatory markers such as ferritin > 300 U/L were observed in the group that presented more changes in liver function markers (ALT, AST, and GGT). Age ≥ 60 years, male sex, AST > 25 U/L, and GGT ≥ 50 or 32 U/L were associated with ALT > 29 U/L. There was a correlation between ALT and AST, LDH, GGT, and ferritin. Our findings suggest that ALT and AST levels may be elevated in patients with long-term COVID, especially in those hospitalised in the acute phase. In addition, ALT > 29 U/L was associated with other markers of liver injury, such as LDH, GGT, and ferritin.
REVIEW | doi:10.20944/preprints202105.0423.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: COVID-19; post-COVID pulmonary fibrosis; lung injury; anti-fibrotic agents
Online: 18 May 2021 (11:32:07 CEST)
Total 219 countries and territories globally suffering from the recent pandemic COVID-19 is now in its second wave with more brutality, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) . It has several symptoms like as persistent fever; respiratory illnesses; cough; fatigue; shortness of breath; loss of appetite; persistent pain or pressure in the chest; dysgeusia; acute respiratory distress syndrome (ARDS) etc., and here the things to worry about is the development of pulmonary fibrosis after COVID-19 in both peoples who had died of due to acute respiratory distress syndrome (ARDS) or those who survived. Due to COVID-19, dysregulated immune response and wound repair mainly in elderly patients causes this secondary pulmonary fibrosis. Thus using anti-fibrotic agents could be meaningful in these circumstances although their efficacy in treating COVID-19 is subject to more detailed laboratory research works. In this review article you will get to know about the lung fibrosis generation due to COVID-19 infection, about anti-fibrotic agents and the currents challenges of this field.
REVIEW | doi:10.20944/preprints202301.0195.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: COVID-19; COVID-19 vaccines; capillary leak syndrome
Online: 11 January 2023 (09:41:36 CET)
Systemic capillary leak syndrome (SCLS) is an uncommon, potentially life-threatening disorder defined as recurrent attacks of pseudo-shock. This syndrome occurs due to the disruption of endothelial cells, which leads to increased vascular permeability, causing intravascular fluid to leak into the extravascular space and albumin to be retained in the interstitial space. SCLS can lead to hypovolemia, peripheral hypoperfusion, and acute renal insufficiency. The syndrome is presented with fever, generalized edema, pleural effusions, dyspnea, hypovolemia, hemoconcentration, prerenal azotemia, shock, and syncope. After ruling out other causes of hypovolemic shock, the diagnosis of SCLS can be considered on the presence of the classical triad of hypotension, hemoconcentration, and hypoalbuminemia. Eliminating the precipitating factors is the cornerstone of SCLS management. It is advisable to be very cautious and weigh the risks and benefits of vaccination of people with a history of this condition. This review will discuss and compare different aspects of SLCS after SARS-CoV-2 infection and COVID-19 vaccination.
REVIEW | doi:10.20944/preprints202007.0426.v1
Subject: Medicine And Pharmacology, Anesthesiology And Pain Medicine Keywords: COVID-19; ARDS; Adenosine; CT-scan; Cytokines Storm
Online: 19 July 2020 (19:31:13 CEST)
Some COVID-19 patients develop interstitial pneumonia that can evolve into Acute Respiratory Distress Syndrome (ARDS). This is accompanied by an inflammatory cytokine storm. SarS-CoV has proteins capable of promoting cytokine storm, especially in patients with comorbidities, including obesity. Since there is currently no resolutive therapy for ARDS and given the scientific literature regarding the use of adenosine, its application has been hypothesized. Adenosine through its receptors is able to inhibit the acute inflammatory process, increase the protection capacity of the epithelial barrier and reduce the damage due to an overactivation of the immune system, such as in cytokine storms. These features are known in ischemia / reperfusion models and could also be exploited in acute lung injury, with hypoxia. In light of these hypotheses, for compassionate use, a COVID-19 patient, with unresponsive respiratory failure, was treated with adenosine. The results showed a rapid and clear improvement in clinical conditions, with the negative effect of detection of SarS-CoV2.
COMMUNICATION | doi:10.20944/preprints202206.0325.v3
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: autonomic failure; lean test; active stand; long covid; Post-COVID-19 condition
Online: 28 July 2022 (03:42:35 CEST)
Autonomic dysfunction is an increasingly recognised complication in chronic neurological conditions such as Parkinson’s disease , and other medical conditions, including diabetes mellitus, chronic fatigue syndrome, postural tachycardia syndrome with and without Ehlers-Danlos syndrome, fibromyalgia and recently Long Covid. Despite laboratory-based tests to evaluate normal and abnormal autonomic function, there are no home-based tests to record neuro-cardiovascular autonomic responses to common stimuli in daily life that are dependent on the normal functioning of the autonomic nervous system. We have developed an adapted blood pressure/heart Autonomic Profile (aAP) that can be used by an individual independently and repeatedly in a domiciliary setting to determine the physiological and symptomatic response to standing, food, and physical and mental (cognitive, emotional) activities. The aAP aids separating autonomic failure (often irreversible) from autonomic dysfunction. This helps the individual and attending healthcare professional understand the relationship between symptoms and common triggers in daily life and informs on self-management in debilitating conditions such as the postural tachycardia syndrome (PoTS) and Long Covid.
ARTICLE | doi:10.20944/preprints202104.0120.v1
Subject: Environmental And Earth Sciences, Environmental Science Keywords: Pre-COVID-19; Post-COVID-19; Secondary Schools; Water Demand; Groundwater; Nigeria
Online: 5 April 2021 (12:22:37 CEST)
The prevalence of corona virus and the novel COVID-19 disease in the entire globe has exacerbated different impact on socioeconomic spectrum in the world, including water use pattern. Thus a research was conducted to examine the comparative use of water during pre- and post-COVID-19 lockdown pattern among post-primary schools in Iwo, Osun State, Nigeria. A survey was conducted among fifteen schools which were randomly selected, but with eight public and seven private schools for the investigation. Both descriptive and inferential statistical techniques were used in data analysis. The results revealed that the major source of water to the schools investigated is ground water which is obtained through hand-dug wells and boreholes. It was further discovered that there was increase in water use during post-COVID-19 lockdown era as a result of the directive by the government that clean water should be provided for hand-washing by all schools regardless of the owner to curtail the spread of COVID-19 disease in the country. One sample t-test also revealed that there was a significant difference in water use at (p<0.01) level. It is recommended that the government and other stakeholders in water sector to ensure that all-time and non-seasonal dependent source of water be provided rather than ground water source which is susceptible to variations in water yields from seasonal variations. This will enable continuous clean water supply, for all purposes, including COVID-19 protocols.
ARTICLE | doi:10.20944/preprints202003.0311.v1
Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: SARS-CoV-2; COVID-19; pathology; post-mortem biopsy
Online: 20 March 2020 (09:24:10 CET)
Data on pathologic changes of the 2019 novel coronavirus disease (COVID-19) are scarce. To gain knowledge about the pathology that may contribute to disease progression and fatality, we performed post-mortem needle core biopsies of lung, liver, and heart in four patients who died of COVID-19 pneumonia. The patients’ ages ranged from 59 to 81, including 3 males and 1 female. Each patient had at least one underlying disease, including immunocompromised status (chronic lymphocytic leukemia and renal transplantation) or other conditions (cirrhosis, hypertension, and diabetes). Time from disease onset to death ranged from 15 to 52 days. All patients had elevated white blood cell counts, with significant rise toward the end, and all had lymphocytopenia except for the patient with leukemia. Histologically, the main findings are in the lungs, including injury to the alveolar epithelial cells, hyaline membrane formation, and hyperplasia of type II pneumocytes, all components of diffuse alveolar damage. Consolidation by fibroblastic proliferation with extracellular matrix and fibrin forming clusters in airspaces is evident. In one patient, the consolidation consists of abundant intra-alveolar neutrophilic infiltration, consistent with superimposed bacterial bronchopneumonia. The liver exhibits mild lobular infiltration by small lymphocytes, and centrilobular sinusoidal dilation. Patchy necrosis is also seen. The heart shows only focal mild fibrosis and mild myocardial hypertrophy, changes likely related to the underlying conditions. In conclusion, the post-mortem examinations show advanced diffuse alveolar damage, as well as superimposed bacterial pneumonia in some patients. Changes in the liver and heart are likely secondary or related to the underlying diseases.
REVIEW | doi:10.20944/preprints202012.0755.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: titin; muscle; diaphragm; atrophy; physical dysfunction, biomarker; urine; post-intensive care syndrome; nutrition; rehabilitation
Online: 30 December 2020 (14:15:47 CET)
Titin is a giant protein that functions as a molecular spring in sarcomeres. Titin interplays the contraction of actin-containing thin filaments and myosin-containing thick filaments. The breakdown product of titin has been measurable in urine as urinary titin N-fragments. Urinary titin N-fragment was originally reported to be a useful biomarker in the diagnosis of muscle dystrophy. Recently, the urinary titin N-fragment has been increasingly gaining attention as a novel biomarker of muscle atrophy and intensive care unit-acquired weakness in critically ill patients, in whom titin loss is a possible pathophysiology. Furthermore, several studies reported that the urinary titin N-fragment also reflected muscle atrophy and weakness in patients with chronic illnesses. It may be used to predict the risk of post-intensive care syndrome or to monitor patients’ condition after hospital discharge for better nutritional and rehabilitation management. We provide several tips on the use of this promising biomarker in post-intensive care syndrome.
ARTICLE | doi:10.20944/preprints202205.0188.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19; HIV; Mortality; cytokine release syndrome
Online: 13 May 2022 (09:47:23 CEST)
Introduction: Established predictors for COVID-19 related mortalities are diverse, with cytokine release syndrome (CRS), a key intermediator to the case fatalities being dominant and multi-faceted. The impact of these several risk factors on coronavirus mortality have been previously reported in several meta‐analyses limited by small sample sizes and premature data, and CRS not fully being accounted for. The objective of this systematic review and meta-analysis was to evaluate the evidence on the risk of COVID-19 related CRS and mortality with HIV serostatus using published data, and a meta-regression to account for possible covariates. Method: Electronic databases including Google Scholar, Cochrane Library, Web of Sciences (WOS), EMBASE, Medline/PubMed, COVID-19 Research Database, and Scopus, were systematically searched till 30th February, 2022. All human studies were included irrespective of publication date or region. Twenty-two studies with a total of 19,783,097 patients detailing COVID-related mortality and eleven with a total of 2,005,274 were included. To pool the estimate, a random-effects model with risk ration as the effect measure was used. Moreover, publication bias and sensitivity analysis were evaluated followed by meta-regression. The trial was registered (CRD42021264761) on the PROSPERO register. Results: The findings were consistent in stating the contribution of HIV infection for COVID-19 related CRS and mortality. The cumulative COVID-19 related mortality and CRS was 110270 (0.6%) and 48863 (2.4%) with total events of 2010 (3.6%), 108260 (0.5%) and 837(4.6%), 48026 (2.4%) among HIV-positive and negative persons respectively. HIV infection showed an increased risk of COVID-19 related CRS and mortality [RR= 1.48, 95% CI (1.16, 1.88) (P=0.002)] and [RR =1.19, 95% CI (1.02 -1.39) (P=0.00001)] respectively, both with substantial heterogeneity (I2 > 80%). The true effects size in 95% of all the comparable populations fell between 0.64 to 2.22 and 0.67 to 3.29 for mortality and CRS respectively. MC studies and COVID-19 mortality with HIV infection showed a significant association [RR = 1.305, 95% CI (1.092 -1.559) (P = 0.003)], similar to studies conducted in America (RR = 1.422, 95% CI 1.233–1.639) and South Africa (RR = 1.123, 95% CI 1.052–1.198). HIV infection showed a risk for ICU admission [(P=0.00001) (I² = 0%)] and mechanical ventilation [(P=0.04) (I² = 0%)] as parameters of CRS. Furthermore, risk of COVID-19 related CRS is influenced by the year a study was conducted (R² = 0.55) and the region (R² = 0.11) same for mortality (R² = 0.60). The variance proportion explained by covariates was significant for CRS (I² = 86.5%, Q = 73.99, df = 10, P = 0.0000) (R² = 0.78) and mortality (I² = 87.5%, Q = 168.02, df = 21, p = 0.0000) (R² = 0.67). Conclusion: Our updated meta-analysis indicated that HIV infection was significantly associated with an increased risk for both COVID-19 – CRS and mortality, which might be modulated by regions, study setting and year. Risk for ICU admission and mechanical ventilation are the key indicators of CRS. We believe the updated data further anchoring CRS will contribute to more substantiation of the findings reported by similar earlier studies (Dong et al., 2021; K. W. Lee et al., 2021; Massarvva, 2021; Mellor et al., 2021; Ssentongo et al., 2021)
HYPOTHESIS | doi:10.20944/preprints202305.0420.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: macrophage-derived chemokine; MDC/CCL22, chemokines; novel coronavirus infection; COVID-19; post-COVID
Online: 6 May 2023 (10:40:04 CEST)
Macrophage-derived chemokine belongs to the CC subfamily. It is produced by dendritic cells (DCs) and macrophages with or without external stimulation. We have previously shown a statistically significant depletion of MDC/CCL22 concentrations in a number of studies concerning COVID-19. These shifts in concentrations demonstrated stability unrelated to the SARS-CoV-2 genetic variant and remained noticeable even in convalescent patients. In this work, we analyze MDC/CCL22 dynamics in various diseases, including those that manifest with inflammation in lung tissue. In addition, we provide our hypothesis on such a decrease in MDC/CCL22 concentrations in COVID-19. If its secretion by producer cells is unperturbed, then it is possible for viral products to bind to this chemokine and to block its functional activity. There is, however, another possible explanation directly linked to depletion in DC subpopulations and the inhibition of their function. We also discuss MDC/CCL22's role in the immunology of novel coronavirus infection, based on both our own data and other studies.
ARTICLE | doi:10.20944/preprints202209.0084.v2
Subject: Medicine And Pharmacology, Pediatrics, Perinatology And Child Health Keywords: long COVID; Post COVID-19 condition; sleep disorders, SARS-CoV-2; Coronavirus; children
Online: 14 October 2022 (10:13:22 CEST)
Acute SARS-CoV-2 infections in children and adolescents are usually mild. However, they can suffer from ongoing symptoms generally referred as long COVID. Sleep disorders are one of the most frequent complaints in long COVID although precise data are missing. We assessed the sleep behavior of children and adolescents who presented at our outpatient clinic between January 2021 and May 2022 with the Children's Sleep Habits Questionnaire (CSHQ-DE). We compared sleep behavior at three different time points: pre-COVID-19, post-COVID-19 at initial presentation and post-COVID-19 at re-presentation. Data from 45 patients were analyzed. Of those, 64% were female and the median age was 10 years (range 0-18 years). Asymptomatic or mild COVID-19 disease was experienced in 89% of patients, whilst 11% experienced moderate disease. Initial presentation occurred at a median of 20.4 weeks (6 weeks - 14 months) after infection. The CSHQ-DE score increased significantly from pre-COVID-19 (45.82+8.7 points) to post-COVID-19 (49.40+8.3 points; p=<0.01). The score then normalized at re-presentation (46.98+7.8; p=0.1). The greatest changes were seen in the CSHQ-DE subscale score "daytime sleepiness". Our data show that children and adolescents with long COVID often suffer from sleep disturbance. For most children and adolescents these sleep disorders decreased over time without further medical intervention, aside from a basic sleep consultation.
Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: SARS; CoV-2; COVID-19; immune system; cytokine
Online: 18 May 2020 (12:46:48 CEST)
Objectives: In December 2019 a novel human-infecting coronavirus, SARS-CoV-2, has emerged. The WHO has stated the epidemic as a “public health emergency of international concern”. A drammatic situation has emerged with thousands of deaths, occurring mainly in the aged and very ill people. Epidemiological studies suggest that immune system function is impaired in elderly individuals and these subjects often present a severe deficiency in nutrients as fatsoluble and hydrosoluble vitamins. Design: In this first part of the review about Cov2 in aged people, we searched for reviews describing the characteristics of autoimmune diseases and the available therapeutic protocols for their treatment. We sed them as a paradigm with the purpose to retrieve pathogenetic mechanisms in common among these pathological conditions and SARS-CoV-2 infection, as well as the alteration induced in immune system function by this virus, or by its homologous SARS-CoV. Results: SARS-CoV-2 infection induces an important immune system dysfunction with the development of an exhuberant proinflammatory response in the host, and with the development of a life-threatening condition defined as Cytokine Release Syndrome (CRS). This leads to the Acute Respiratory Syndrome (ARDS), mainly in the aged people. High mortality and lethality rates have been observed in the elderly subjects with CoV-2-related infection. Conclusion: These diseases may serve as a paradigm for the study of CRS emerging in the course of SARS CoV-2 infection. This review discusses about the possible activity of Vitamin A, D, E and C in restoring normal antiviral Immune System function or the potential therapeutic role of these micronutrients as a part of a multi-treatment strategy against SARS- CoV-2 infection.
ARTICLE | doi:10.20944/preprints202209.0400.v1
Subject: Medicine And Pharmacology, Psychiatry And Mental Health Keywords: COVID 19; health personnel; Burnout, Psychological; COVID 19 stress syndrome
Online: 26 September 2022 (11:42:28 CEST)
Purpose: The healthcare pressure and emotional tension during the first year of the COVID 19 pandemic have been able to affect the health of healthcare personnel. Physical and psychological symptoms attributed to a work situation and or COVID 19 infection are describ ed in health professionals. Objective: to analyze the prevalence of physical and psychological symptoms directly or indirectly related to COVID 19 (occupational causes, illness or persistent COVID 19) after a 12 month pandemic. Methods: #COVID19PS is a cro ss sectional analytical study using an ad hoc questionnaire distributed through social media to record physical and psychological symptoms related to COVID 19 in health professionals. Variables: age, sex, geographical origin, profession, characteristics of the work environment, physical symptoms, Maslach test ( for health professionals. Univariate and bivariate statistical analysis using t distribution, Chi square, ANOVA using IBM SPSS v20®. Results: N=1.159 ( women, 21.8% men; 44.6% <35 years old, 23.9% between 35 45years); 96.5% Spaniards. Professions: 17.1% medicine, 12.7% nursing, 32% physiotherapy, 24.1% occupational therapy, 14.1% others; 47.5% belonged to direct care for COVID 19 patients. 28.2% had passed the disease and 3.7% had it acti ve. 61.6% had physical symptoms ( neurological, 31.7% musculoskeletal, 29.6% general, 20.9% gastrointestinal, 20.3% skin, 19.2% cardiovascular, 16% respiratory (p= 96.9% had a medium high Burnout index (p= 48.3% with high levels of Emot ional Exhaustion, 62.9% with medium high level of Depersonalization and 74% with medium low levels of Personal Accomplishment. Conclusion: all health professions present high rates of physical and burnout consequences of the first year of COVID 19 pandemic.
ARTICLE | doi:10.20944/preprints202303.0474.v1
Subject: Public Health And Healthcare, Public Health And Health Services Keywords: Covid-19; children and adolescents; Rwanda; structural inequalities; post colonialism
Online: 28 March 2023 (05:33:08 CEST)
COVID-19, the fear it engendered, and the policy measures to manage its spread have disproportionately impacted the wellbeing of children and adolescents (CAs). We present an intensive critical realist case study of the impact of COVID-19 on the health and wellbeing of CAs in Rwanda, seeing it as much a social and political crisis as a medical and public health one. To do this, we carried out interviews with a purposive sample of 25 leaders with a working knowledge of children and young people; they were more likely than the CAs themselves to observe changes across the CA population within their remit and more likely to be looking for general explanations rather than individual experiences. The findings show that CAs' responses to the changes wrought on their lives by Covid-19 were conditioned by their age, gender, social class and if they lived in urban or rural areas. However, Covid19 has not just revealed the structural weakness of the Rwandan health system but of education, social protection, child protection, employment, family, and financial systems. The pathway to (adverse) impacts of COVID-19 on CAs is conditioned by these institutions and their interactions together with structural socioeconomic inequalities both within Rwanda and globally.
COMMUNICATION | doi:10.20944/preprints202003.0445.v1
Subject: Social Sciences, Geography, Planning And Development Keywords: international tourism; coronavirus; COVID-19; post-viral tourism; recovery strategies
Online: 31 March 2020 (05:00:08 CEST)
The coronavirus pandemic will deeply affect the tourism and travel sector. It is already clear now that its economic impact would be more severe that in the case of the Severe Acute Respiratory Syndrome (SARS) in 2002-2003. Although not as deadly as SARS, coronavirus infection has a longer incubation period and leaves about 85% of the infected without any (or with just mild) symptoms which makes it more difficult to track and to contain. Moreover, it appears to be much more contagious than its predecessor. The goods news is that most people recover from the disease and develop antibodies that can protect them from getting infected again (natural vaccination). Those cured might become the key element for the post-virus recovery strategies of tourism organisations. People with the acquired immunity to the virus would be capable of travelling freely without spreading the disease. Airlines, hotels and gastronomy should aim at this group offering them discounts and special offers. However, the problem is how to effectively ensure that everyone who claims to be cured from COVID-19 is telling the truth. Health tracking bracelets, apps, and other advanced technological solutions should be put in place. Recent best practices from Hong Kong, mainland China, or India might be applied.
ARTICLE | doi:10.20944/preprints202006.0245.v1
Subject: Biology And Life Sciences, Endocrinology And Metabolism Keywords: COVID-19; Metabolic syndrome; Comorbidity; Enrichment analysis; biological processes and pathways
Online: 21 June 2020 (09:52:10 CEST)
The risk factors associated with COVID-19 related severity, morbidity, and mortality, i.e., obesity (often associated with NAFLD), hyperglycemia, hypertension and dyslipidemia all cluster together as metabolic syndrome (MetS). Instead of studying association of these risk factors with COVID-19, it makes sense studying the association between MetS on one hand and COVID-19 on the other. This study explores a molecular basis underpinning the above association. Severity of COVID-19 patients with MetS could be due to functional alterations of host proteins due to their interactions with viral proteins. We collected data from Enrichr (https://amp.pharm.mssm.edu/Enrichr/), DisGeNET (https://www.disgenet.org/) and others and carried out enrichment analysis using Enrichr. Various biological processes and pathways associated with viral protein interacting partners are known to involve in metabolic diseases. The molecular pathways underlying insulin resistance, insulin signaling and insulin secretion are not only involved in diabetes but also in CVD and obesity (associated with non-alcoholic fatty liver disease; NAFLD). Lipid metabolism/lipogenesis, fatty acid oxidation and inflammation are associated with MetS. Viral interacting host proteins are associated and enriched with terms like hyperglycemia, coronary artery disease, hypertensive disease related to CVD and liver diseases in DisGeNET. Association of viral interacting proteins with disease-relevant biological processes, pathways and disease-related terms suggests that altered host protein function following interaction with viral proteins might contribute to frequent occurrence and/or severity of COVID-19 in subjects with MetS. Such analysis not only provides a molecular basis of comorbidity but also incriminates host proteins in viral replication, growth and identifies possible drug targets for intervention.
ARTICLE | doi:10.20944/preprints202006.0103.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: clinical medecine; physiopathology; COVID-19; neurological manifestations; kidney disease; cytokine; corticosteroids; intravenous immunoglobulins
Online: 7 June 2020 (15:50:37 CEST)
Severe disease and uremia are risk factors for neurological complications of coronavirus disease-2019 (COVID-19). An in-depth analysis of a case series was conducted to describe the neurological manifestations of patients with COVID-19 and gain pathophysiological insights that may guide clinical decision-making – especially with respect to the cytokine release syndrome (CRS). Extensive clinical, laboratory, and imaging phenotyping was performed in five patients. Neurological presentation included confusion, tremor, cerebellar ataxia, behavioral alterations, aphasia, pyramidal syndrome, coma, cranial nerve palsy, dysautonomia, and central hypothyroidism. Neurological disturbances were remarkably accompanied by laboratory evidence of CRS. SARS-CoV-2 was undetectable in the cerebrospinal fluid. Hyperalbuminorachy and increased levels of the astroglial protein S100B were suggestive of blood-brain barrier (BBB) dysfunction. Brain MRI findings comprised evidence of acute leukoencephalitis (n = 3, of whom one with a hemorrhagic form), cytotoxic edema mimicking ischemic stroke (n = 1), or normal results (n = 2). Treatment with corticosteroids and/or intravenous immunoglobulins was attempted – resulting in rapid recovery from neurological disturbances in two cases. Patients with COVID-19 can develop neurological manifestations that share clinical, laboratory, and imaging similarities with those of chimeric antigen receptor-T cell-related encephalopathy. The pathophysiological underpinnings appear to involve CRS, endothelial activation, BBB dysfunction, and immune-mediated mechanisms.
ARTICLE | doi:10.20944/preprints202206.0080.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: COVID-19 reactions; ITP syndromes 2; COVID-vaccine women susceptibility
Online: 6 June 2022 (09:43:09 CEST)
Vaccination is the most promising approach for ending or containing the SARS-CoV2 pandemic. However, serious post-COVID vaccine reactions including immunocytopenia (ITP) syndrome has been increasingly reported. Several factors cause increased risks including multiple doses, age-dependent heterogeneity in immune-responses, platelet cross-reactions with microbial components, and Long-COVID syndrome. Thus, in the absence of a widely available specific therapeutics, vigilance is important while more studies are imperative. Using a structured questionnaire sent to different regions in Saudi Arabia, we conducted a comprehensive investigation on the frequency, rates, disease patterns, and patient demographics of post-COVID-19 side effects on febrile patients after three major vaccines. Results indicated the majority administered Pfizer BioNtech vaccine (81%, n=809); followed by AstraZeneca (16%, n=155); and Moderna (3%, n=34). In overall 998 participants, 74% (n=737) had no serious symptoms; however, 26.2% (n=261) revealed typical syndrome. In a focused group of 722, shortness of breath (20%), bruises or bleeding (18%), inattention (18%), GIT symptoms (17.6%), skin irritation (8.6%), and anosmia and ageusia (8%) were the most prominent. The onset time was mostly in 1-3 days in 49% (n=128), followed by 4-7 days in 21.8% (n=57), 8-14 days in 16.5% (n=43), and more than a month in 12.6% (n=33). The onsets occurred mostly after the first, second, or both doses 9%, 10%, and 7%, respectively. The frequency of symptoms was significantly higher among after Moderna ® vaccine (P-value = 0.00006) and it was significantly lower in participants who received Pfizer (P-value 0.00231). We did not find significant difference in symptoms related to differences in regions. Similarly, the region, age, gender, education, and nationality had no influence in the dose and onset timings. The findings of this study have significant clinical implications in disease management strategies, preventive measures, and vaccine development. Future vertical studies would reveal more insights into the mechanisms of post-COVID vaccine syndrome.
ARTICLE | doi:10.20944/preprints202212.0415.v1
Subject: Social Sciences, Media Studies Keywords: stigma; news frame; monkeypox; COVID-19; The Washington Post; online news
Online: 22 December 2022 (03:42:16 CET)
Abstract: Background: Stigma in health can result in a broad range of vulnerabilities and risk for patients and healthcare providers. The media plays a role in people’s understanding of health and stigma is socially constructed through many communication channels including via media framing. Among health issues that were affected by stigma recently were the Monkeypox and Covid-19. Objectives: This research aims to examine how The Washington Post framed stigma around mon-keypox and COVID-19. Guided by the framing theory and stigma theory, online news coverage for monkeypox and COVID-19 were analyzed to understand the construction of social stigma through the media reporting. Methods: This research employed a qualitative content analysis to compare news framing in The Washington Post online news regarding monkeypox and COVID-19. Results: Based on endemic, reassurance, and sexual transmission frames, the The Washington Post predominantly defined Africa as the source of the disease, blames gay communities, and empha-sizes no need to worry about the spread of the monkeypox virus. For the COVID-19 coverage, The Washington Post described China as the source of the coronavirus and constructs the image of panic towards the spread of the virus. Conclusions: The shifts in stigma discourse essentially manifest racism, xenophobia, and sexism in public health. This research affirms that the media reinforces stigma phenomenon in health through framing and offers constructive suggestions for mitigating this issue.
ARTICLE | doi:10.20944/preprints202011.0422.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Depression; anxiety; stress; university healthcare workers; COVID-19; post–movement lockdown
Online: 16 November 2020 (13:46:33 CET)
This study investigated the prevalence and severity of depression, anxiety, and stress and determined the association between various factors, social support, and depression and anxiety among university healthcare workers in Malaysia after the government lifted the movement control order (MCO) put in place to curb the coronavirus disease 2019 (COVID-19) pandemic. This online, cross-sectional survey recruited 399 participants from two university hospitals, and they were administered a self-reported questionnaire on demographic, personal, and clinical characteristics; COVID-19-related stressors; and coping. In addition, they completed the Multidimensional Scale of Perceived Social Support (MSPSS) to measure perceived social support, as well as the 21-item Depression, Anxiety, and Stress Scale (DASS-21) to assess depression, anxiety, and stress. We found that the prevalence of depression, anxiety, and stress were 21.8%, 31.6%, and 29.1%, respectively. Participants with moderate to extremely severe depression, anxiety, and stress made up 13.3%, 25.8%, and 8.1% of the sample, respectively. Being single or divorced, fear of frequent exposure to COVID-19 patients, those who agreed that their area of living had a high prevalence of COVID-19 cases, and uncertainty regarding the prevalence of COVID-19 cases in the area of living were associated with higher odds of depression and anxiety. Conversely, having more than three children and greater perceived friend support were associated with lower odds of depression and anxiety. The prevalence of depression, anxiety, and stress remained elevated even after the MCO was lifted.
COMMUNICATION | doi:10.20944/preprints202004.0197.v2
Subject: Social Sciences, Psychology Keywords: COVID-19; Post Traumatic Stress Disorder (PTSD); victims; psychological problems; counseling
Online: 30 April 2020 (05:40:55 CEST)
Since January, the disease caused by the Sars Cov-2 virus has spread and following pandemic. In a few months, the virus is seriously affecting the health systems of the various countries of the world and placing people in difficult psychological conditions. Few scientific resources on mental health have been published but still no one has proposed an action plan to cope the future psychological problems.This manuscript provides a plan to easily frame the priorities of mental health area related to COVID-19 to be taken into consideration which should be disseminated and that should be known by all health professionals and also by the major administrators of public health.
Subject: Biology And Life Sciences, Virology Keywords: SARS-CoV-2; Covid-19; Dog; Connecticut; Epidemiology
Online: 18 March 2021 (10:56:35 CET)
We report the first detection of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus from a dog in Connecticut during February 2021. Complete genome sequencing and phylo-genetic analysis of the hCoV-19/USA/CT-CVMDL-Dog-1/2021 (CT_Dog/2021) virus were con-ducted to identify the origin and lineage of the virus. The CT_Dog/2021 virus belonged to the GH/B1.2. genetic lineage and was genetically close to SARS-CoV-2 identified from humans in the U.S. during the winter of 2020-2021. However, it was not related to other SARS-CoV-2 identified from companion animals in the U.S. It contained both D614G in spike and P323L in nsp12 substitutions which have become the dominant mutations in the United States. The continued sporadic detections of SARS-CoV-2 in companion animals warrant public health concerns about their potential to become a new reservoir species of SARS-CoV-2.
ARTICLE | doi:10.20944/preprints201911.0061.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: rett syndrome; intrinsically disordered region; phylogenetic profile analysis; post-transcriptional modification; methyl-cpg-binding protein 2; cyclin-dependent kinase-like 5; forkhead box protein g1
Online: 6 November 2019 (10:58:54 CET)
Rett syndrome (RTT), a neurodevelopmental disorder, is mainly caused by mutations in methyl CpG-binding protein 2 (MECP2), which alter the functions of domains to either bind to methylated DNA or interact with a transcriptional co-repressor complex. It has been established that alterations in cyclin-dependent kinase-like 5 (CDKL5) or forkhead box protein G1 (FOXG1) correspond to distinct neurodevelopmental disorders, given that a series of studies have indicated that RTT is also caused by alterations in either one of these genes. We tried to elucidate RTT through evolution and structure assessment of MeCP2, CDKL5, and FOXG1, by focusing on their binding partners and disordered structures. Here, we provide insight into the similarities of the FOXG1 and MECP2 binding partners evolution and function. On the other hand, we suggest that CDKL5 could be a potential candidate for a classical RTT treatment, particularly based on its disordered structure that spans after the catalytic domain to the C-terminus, which shows abundant linear motifs that can bind to molecules with divergent structures of similar affinity. Additionally, we provide insight into the relationship between disordered structure and disease.
ARTICLE | doi:10.20944/preprints202212.0410.v1
Subject: Medicine And Pharmacology, Clinical Medicine Keywords: Heart rate variability; COVID-19; post-COVID-19 condition; long COVID; autonomic dysfunction; vagal nerve activity; symptomatology; lung function
Online: 22 December 2022 (03:13:53 CET)
Persistence of symptoms beyond three months after COVID-19 infection, often referred to as post-COVID-19 condition (PCC), is commonly experienced. It is hypothesized that PCC results from autonomic dysfunction with decreased vagal nerve activity, which can be indexed by low heart rate variability (HRV). The aim of this study was to assess the association of HRV upon admission with pulmonary function impairment and number of reported symptoms beyond three months after initial hospitalization for COVID-19 between February and December 2020. Follow-up took place three to five months after discharge and included pulmonary function tests and the assessment of persistent symptoms. HRV analysis was performed on one 10s electrocardiogram obtained upon admission. Analyses were performed using multivariable and multinomial logistic regression models. Among 171 patients who received follow-up, and with an electrocardiogram at admission, decreased diffusion capacity of the lung for carbon monoxide (DLCO) (41%) was most frequently found. After a median of 119 days (IQR 101-141), 81% of the participants reported at least one symptom. HRV was not associated with pulmonary function impairment or persistent symptoms three to five months after hospitalization for COVID-19.
REVIEW | doi:10.20944/preprints202006.0045.v1
Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: ARDS; COVID-19; Berlin Criteria; Respiratory Failure
Online: 5 June 2020 (13:54:36 CEST)
Introduction: The exponential growth of the SARS-CoV-2 virus transmission during the first months of 2020 has placed substantial pressure on health systems worldwide. The complications derived from the novel coronavirus disease (COVID-19) vary in due to comorbidities, sex and age, with more than 50% of the patients who require some level of intensive care developing acute respiratory distress syndrome (ARDS). Areas covered: Various complications caused by SARS-CoV-2 infection have been identified, the most lethal being the acute respiratory distress syndrome, caused most likely by the presence of severe immune cell response and the concomitant alveolus inflammation. The authors carried out an extensive and comprehensive literature review on SARS-CoV-2 infection, the clinical, pathological and radiological presentation as well as the current treatment strategies. Expert Opinion Elevation of inflammatory biomarkers is a common trend among seriously ill patients. The information available strongly suggests that in COVID-19 patients, their altered immune response, including a massive cytokine storm, is responsible for the further damage evidenced among ARDS patients. The increasingly high number of scientific articles and evidence available can only suggest that the individualization of each case is the norm, not all patients with acute respiratory failure due to COVID-19 meet the Berlin definition and therefore ARDS should be considered as a heterogeneous disease, with a wide range in the expression of its severity and clinical manifestations.
ARTICLE | doi:10.20944/preprints202204.0296.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: dapsone; disulfiram; chronic Lyme disease; Post-Treatment Lyme Disease Syndrome; babesia; bartonella; persisters; biofilms.
Online: 29 April 2022 (10:12:41 CEST)
Lyme disease and associated co-infections are increasing worldwide and approximately 20% of individuals develop chronic Lyme disease (CLD)/Post-Treatment Lyme Disease Syndrome (PTLDS) despite early antibiotics. A 7–8-week protocol of double dose dapsone combination therapy (DDDCT) for CLD/PTLDS results in symptom remission in approximately 50% of patients for one year or longer, with published culture studies indicating higher doses of dapsone demonstrate efficacy against resistant biofilm forms of Borrelia burgdorferi. The purpose of this study was therefore to evaluate higher doses of dapsone in the treatment of resistant CLD/PTLDS and associated co-infections. Twenty-five patients with a history of Lyme and associated co-infections, most of whom had ongoing symptoms despite several courses of DDDCT, took one or more courses of high dose pulsed dapsone combination therapy (200 mg dapsone X 3-4 days and/or 200 mg BID x 4 days), depending on persistent symptoms. The majority of patients noticed sustained improvement in 8 major Lyme symptoms, including fatigue, pain, headaches, neuropathy, insomnia, cognition, and sweating, where dapsone dosage, not just treatment length, positively affected outcomes. High dose pulsed dapsone combination therapy may represent a novel therapeutic approach for the treatment of resistant CLD/PTLDS, and should be confirmed in randomized, controlled clinical trials.
REVIEW | doi:10.20944/preprints202012.0466.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19; SARS-CoV-2; Opsoclonus; myoclonus; parainfectious
Online: 18 December 2020 (12:19:07 CET)
Opsoclonus-myoclonus-ataxia syndrome is a heterogeneous constellation of symptoms ranging from full combination of these three neurological findings to varying degree of isolated individual sign. Since the emergence of coronavirus disease 2019 (COVID-19), neurological symptoms, syndromes and complications associated with this multi-organ viral infection have been reported and the various aspects of neurological involvement are increasingly uncovered. As a neuro-inflammatory disorder in nature, one would expect to observe opsoclonus-myoclonus syndrome after a prevalent viral infection in a pandemic scale, as it has been the case for many other neuro-inflammatory syndromes. We report seven cases of opsoclonus-myoclonus syndrome presumably para-infectious in nature and discuss their phenomenology, their possible pathophysiological relationship to COVID-19 and diagnostic and treatment strategy in each case. Finally we review the relevant data in the literature regarding the opsoclonus-myoclonus syndrome and possible similar cases associated with COVID-19 and its diagnostic importance for clinicians in various fields of medicine encountering COVID-19 patients and its complications.
REVIEW | doi:10.20944/preprints202105.0264.v1
Subject: Social Sciences, Anthropology Keywords: COVID-19; critical scrutiny; logic; pandemic; response; SARS-CoV-2
Online: 12 May 2021 (10:48:05 CEST)
Part of philosophy is to subject assertions to critical scrutiny, clarifying exactly what the assertion is saying, its implications, and thus its direct plausibility. The goal is to ensure clarity, logical consistency, and rational argumentation in order to arrive at reasoned conclusions. A common problem is that arguments have missing implied premises that, unless explicitly stated, are mistakenly assumed to be true. Here we subject conclusions made regarding the SARS-CoV-2 pandemic to critical scrutiny, revealing their implied premises so that these premises can be explicitly examined and refuted. Specifically, we refute the conclusions that “no one is protected until everyone is protected” and “population lockdowns are required to protect those at high risk of adverse outcomes.” In the end, we argue for the conclusion that “an Emergency Management principles based response to the pandemic, compared to population-wide lockdowns, offers a way to prevent more adverse outcomes from COVID-19, better prevent overwhelmed healthcare, and prevent most of the collateral damage to the wellbeing of the population that has resulted from the lockdowns.”
ARTICLE | doi:10.20944/preprints202103.0609.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: SARS-CoV-2; COVID-19; Aerosols; Environmental Surveillance; Air Sampling
Online: 24 March 2021 (17:29:23 CET)
The worldwide spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has ubiquitously impacted many aspects of life. As vaccines continue to be manufactured and administered, limiting the spread of SARS-CoV-2 will rely more heavily on the early identification of contagious individuals occupying reopened and increasingly populated indoor environments. In this study, we investigated the utility of an impaction-based aerosol sampling system with multiple nucleic acid collection media. Heat-inactivated SARS-CoV-2 was utilized to perform bench-scale, short-range aerosol, and room-scale aerosol experiments. Through bench-scale experiments, AerosolSense Capture Media (ACM) and nylon flocked swabs were identified as the highest utility media. In room-scale aerosol experiments, consistent detection of aerosol SARS-CoV-2 was achieved at a concentration equal to or greater than 0.089 genome copies per liter of room air (gc/L) when air was sampled for eight hours or more at less than one air change per hour (ACH). Shorter sampling periods (~75 minutes) yielded consistent detection at ~31.8 gc/L of room air and intermittent detection down to ~0.318 gc/L at (1 and 6+ ACH respectively). These results support further exploration in real-world testing scenarios and suggest the utility of indoor aerosol surveillance as an effective risk mitigation strategy in occupied buildings.
ARTICLE | doi:10.20944/preprints202005.0271.v1
Subject: Biology And Life Sciences, Virology Keywords: COVID-19; SARS-CoV-2; de novo vaccine; epitope; immunity
Online: 16 May 2020 (17:07:43 CEST)
Currently, with a large number of fatality rates, coronavirus disease-2019 (COVID-19) has emerged as a potential threat to human health worldwide. It has been well-known that severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is responsible for COVID-19 and World Health Organization (WHO) proclaimed the contagious disease as a global pandemic. Researchers from different parts of the world amalgamate together inquest of remedies for this deadly virus. Recently, it has been demonstrated that the spike glycoprotein (SGP) of SARS-CoV-2 is the mediator behind the entrance into the host cells. Our group has comprehensibly analyzed the SGP of SARS-CoV-2 through multiple sequence analysis along with the phylogenetic analysis. Further, this research work predicted the most immunogenic epitopes for both B-cell and T-cell. Notably, we focused mainly on major histocompatibility complex (MHC) class I potential peptides and predicted two epitopes; WTAGAAAYY and GAAAYYVGY, that bind with the MHC class I alleles which are further validated by molecular docking analysis. Furthermore, this study also proposed that the selected epitopes were shown availability in a greater range of the population. Hence, our study comes up with a strong base for the implementation of designing novel vaccine candidates against SARS-CoV-2, however adequate laboratory works will need to be conducted for the appropriate application.
ARTICLE | doi:10.20944/preprints202112.0374.v1
Subject: Medicine And Pharmacology, Psychiatry And Mental Health Keywords: COVID-19 pandemic; children and adolescents; machine learning; post-hoc explainability; model calibration
Online: 22 December 2021 (16:21:19 CET)
The global spread of COVID-19 led the World Health Organization to declare a pandemic on 11 March 2020. To decelerate this spread, countries have taken strict measures that affected the lifestyle and economy. Various studies have been focused on the identification of COVID-19 impact to mental health of children and adolescents via traditional statistical approaches. However, a machine learning methodology must be developed to explain the main factors that contribute to the change of mood state of children and adolescents during the first lockdown. Therefore, to this study an explainable machine learning pipeline is presented focusing on children and adolescents in Greece, where a strict lockdown was imposed. The target group consists of children and adolescents, recruited from children and adolescent mental health services, who present mental health problems diagnosed before the pandemic. The proposed methodology imposes: (i) data collection via questionnaires; (ii) a clustering process to identify the groups of subjects with amelioration, deterioration and stability to their mood state; (iii) a feature selection process to identify the most informative features that contribute to mood state prediction; (iv) a decision-making process based on an experimental evaluation among classifiers; (v) calibration of the best performing model and (v) a post-hoc interpretation of the features’ impact on the best performing model. The results showed that a blend of heterogeneous features from almost all feature categories is necessary to increase our understanding regarding the effect of COVID-19 pandemic on the mood state of children and adolescents.
ARTICLE | doi:10.20944/preprints202107.0473.v1
Subject: Business, Economics And Management, Accounting And Taxation Keywords: mental health; perceived stress; university students; gender differences; COVID-19; post-lockdown; Romania
Online: 21 July 2021 (09:38:11 CEST)
The rapid spread of COVID-19 worldwide was accompanied by intense fears, confusion, worries, anger and stress threatening people’s mental health. Unprecedented measures to slow down and prevent the transmission of COVID-19 have had various impacts on the population’s health behaviour and mental health. The main purpose of the present study is to investigate the lockdown’s effects on university students’ mental health in Romania. Based on a cross-sectional design, the survey data were collected from a sample of 722 participants (247 males; M = 21.1 years; SD ± 1.73). A path analysis was performed to verify the hypothesised direct and indirect effects included in the multiple mediation model. The findings showed a positive association between stress and boredom proneness, missing daily social interactions, spending more time on phone conversations and the increasing interest in following news about the pandemic. The path analysis revealed an excellent fit between the proposed multiple mediation model and the sample data. Boredom proneness and missing daily social interactions both affected stress, directly and indirectly, through more time spent on phone conversations. In addition, it was found that the increased interest in following news about the pan-demic mediated the relationship between boredom proneness and perceived stress. In terms of gender differences, our findings revealed that female students experienced significantly higher stress levels than male students, perceived to a greater extent the lack of daily social interactions and spent more time on phone conversations. Overall, the findings further extend the empirical evidence on university students’ mental health in the context of the COVID-19 pandemic. Therefore, universities need to organise support programmes focused on developing university students’ coping strategies to maintain their mental health even in adverse contexts.
ARTICLE | doi:10.20944/preprints202009.0690.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: COVID-19 Pandemic; Finland; health care personnel; psychological distress; post-traumatic stress disorder
Online: 28 September 2020 (15:37:39 CEST)
On March 2020 strict measures took place in Finland to limit the COVID -19 pandemic. A majority of the Finnish COVID -19 –patients have been located in the southern Finland and consequently cared for in the HUS Helsinki University Hospital. During the ongoing pandemic, HUS personnel’s psychological symptoms are followed via an electronic survey, which also delivers information on psychosocial support services. The baseline survey in June 2020 was sent to 25494 HUS employees out of whom 4804 (19%) answered; altogether 62.4% of the respondents were nursing staff and 8.9% medical doctors. While the follow-up continues for a year and a half, this report shares the sociodemographic characteristics of the respondents and the first results of psychological symptoms from the baseline survey. Out of those who were directly involved in pandemic patients` care, 43.4% reported potentially traumatic COVID-19 pandemic-related experiences vs. 21.8% among the other (p < 0.001). While over a half of the personnel was symptomless, a group of respondents reported pandemic work –related traumatic events and concurrent depressive, insomnia and anxiety symptoms. This highlights the need to ensure appropriate psychosocial support services to all traumatized personnel and PTEs were present especially among nursing staff.
ARTICLE | doi:10.20944/preprints202112.0117.v1
Subject: Computer Science And Mathematics, Artificial Intelligence And Machine Learning Keywords: post-editing; machine translation; Portuguese; English; translationese; post-editese
Online: 8 December 2021 (09:43:11 CET)
In the present study, we investigate the post-editese phenomenon, i.e., the unique features that set machine translated post-edited texts apart from human-translated texts. We use two literary texts, namely, the English children's novel by Lewis Carroll Alice’s Adventures in Wonderland (AW) and Paula Hawkins' popular book The Girl on the Train (TGOTT) translated from English into Brazilian-Portuguese to investigate whether the post-editese features can be found on the surface of the post-edited (PE) texts. In addition, we examine how the features found in the PE texts differ from the features encountered in the human-translated (HT) and machine translation (MT) versions of the same source text. Results revealed evidence for post-editese for TGOTT only with PE versions being more similar to the MT output than to the HT texts.
Subject: Physical Sciences, Astronomy And Astrophysics Keywords: Hypothesis, Fission, Heavy Post-Post-Fe Elements, Solar System
Online: 23 July 2019 (11:17:56 CEST)
Conventional models do not fully explain composition of the solar system – for example, the presence of p-nuclei and post-post-Fe-nuclei remains not yet understood (and is one of the great unresolved puzzles of nuclear astrophysics in general); other puzzles exist. We offer a hypothesis which can explain the appearance of non-native elements in the solar system, and a feasible scenario for its implementation. The hypothesis suggests that a nuclear-fission "event" occurred in the inner part of the solar system at the time currently defined as the birth of the system. Conventional models have never considered fission as a contributing nuclei-production mechanism. Upon examination of the existing models and factual data (presented in volumes of publications but never combined into an aggregate), we identified one plausible scenario by which a fission event (not demolishing the entire solar system) could occur: an encounter with a compact super-dense stellar "fragment" (with specific properties) and its "explosion" in fission-cascades. Such scenario also helps resolve other long-standing puzzles of the solar system. For example, it provides that the fission-produced nuclei subsequently transformed into the material that (eventually) accreted into the "rocky" objects in the system (terrestrial planets, asteroids, etc.) and enriched the pre-existed hydrogen-helium objects (the Sun and the gaseous giants) – this offers an explanation for the planets’ inner position and compositional differences within the predominantly hydrogen-helium rest of the solar system. Other implications also follow.
ARTICLE | doi:10.20944/preprints202210.0158.v2
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: severe acute respiratory syndrome coronavirus 2; SARS-CoV-2; COVID-19; accessory protein; mapping; structure; Open reading frame, Orf.
Online: 3 November 2022 (10:27:01 CET)
The COVID-19 pandemic first observed in December 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has influenced every individual on the planet. The virus has influenced our lifestyle, education, economy and the environment. Though the vaccines against COVID-19 have provided protection against the disease; new strains of the virus have lowered the efficiency of the vaccines. There is still no effective therapy for the treatment of the disease. Understanding the protein structure of the virus may lead to the development of effective therapies for the disease. We recently mapped the structural proteins and non-structural proteins of SARS-CoV-2. The accessory proteins (Open reading frames, Orfs) of SARS-CoV-2 modulate the host environment to favor virus replication. This paper reports mapping the accessory proteins (Orfs) of SARS-CoV-2.
BRIEF REPORT | doi:10.20944/preprints202105.0187.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: SARS-CoV-2; stools; COVID-19; MIS-C; children
Online: 10 May 2021 (13:00:43 CEST)
Multisystem inflammatory syndrome related to SARS-CoV-2 infection (MIS-C) is a rare severe illness affecting pediatric patients. No data are available in literature about the presence of SARS-CoV-2 RNA in faeces in patients with MIS-C. The SARS-CoV-2 positivity was evaluated in fecal samples obtained in a prospective cohort of pediatric patients admitted to our tertiary Hos-pital and diagnosed with MIS-C or COVID-19 between April 15, 2020, and February 29, 2021. The real-time RT-PCR was performed using a validated kit. The assay measures 3 target genes: SARS-CoV-2 gene E, gene N, gene ORF1ab. Overall, 16/63 (25%) fecal samples revealed the pres-ence of SARS -CoV-2 RNA. No differences were detected about time from presumptive viral ex-posure and the time of stool collection (14 vs 8 days, p> 0,05) as well as about the presence of gas-trointestinal symptoms (p>0.05) between patients with positive (+) stools for SARS-CoV-2 RNA and patients tested negative (-). Among children with MIS-C, stools were collected 27.5 days as median (95% CI 14-34) after presumed contact and the positivity rate was 12.5% (4/32). According to our data, we could suggest contact precautions with all patients with MIS-C. Further sample collection is ongoing to verify our preliminary data.
ARTICLE | doi:10.20944/preprints201812.0083.v1
Subject: Biology And Life Sciences, Ecology, Evolution, Behavior And Systematics Keywords: post-mining regeneration; succession; tropical dry forest; post-mining recovery
Online: 6 December 2018 (11:04:06 CET)
Open pit mining is a common activity in the Yucatan peninsula for the extraction of limestone. This mining is known under the generic name of quarries, and regionally as sascaberas (sascab=white soil in Mayan language). These areas are characterized by the total removal of the natural vegetation cover and soil in order to have access to the calcareous material. The present study shows the composition and structure of the vegetation in five quarries after approximately ten years of abandonment, and the conserved vegetation near to each one of the quarries in southeastern Quintana Roo. Using a canonical correspondence analysis (CCA), the distribution of the species was determined in relation to the edaphic variables: soil depth, percentage of organic matter (OM), cationic exchange capacity (CEC), pH and texture. 26 families, 46 genera and 50 species were recorded in the quarries and 25 families, 45 genera and 47 species were recorded in the conserved areas. The dominant species in the quarries belong to the families Poaceae, Fabaceae, Rubiaceae and Anacardiaceae. The quarries with higher values of OM (1.63%), CEC (24.05 Cmol/kg), depth (11 cm) and sand percentage (31.33%) include the following species like Lysiloma latisiliquum, Metopium brownei and Bursera simaruba which are commonly found in secondary forests. On the other hand, quarries with lower values of OM (0.39%), CEC (16.58 Cmol/kg) and depth (5.02), and higher percentage of silt (42.44%) were dominated by herbaceous species belonging to the Poaceae family and by Borreria verticillata, which are typical in disturbed areas of southeastern Mexico. In all cases, the pH was slightly alkaline due to the content of calcium carbonate (CaCO3), characteristic of the soils of the region. The edaphic variables are significantly correlated with the development and distribution of vegetation, and with the structure of the communities.
ARTICLE | doi:10.20944/preprints202305.0510.v1
Subject: Social Sciences, Education Keywords: COVID-19; Post-Pandemic; Higher Education; Online Learning; Global Citizenship; Hiroshima; Japan; Students’ Perception
Online: 8 May 2023 (10:20:14 CEST)
The COVID-19 pandemic has struck educational experience systems around the globe. This paper investigates and evaluates the student participants’ perceptions who joined the international exchange seminar on global citizenship and peace held at a University in Hiroshima, Japan. Approximately seventy students and faculty members from nine to ten different universities from around the globe joined this summer program in August 2021 (online) and 2022 (face-to-face). This study is a mixed-method study. The first part consists of a quantitative analysis of BEVI data obtained from the students in the seminar before COVID-19 and after. The research concludes that there are no changes in the way students learn. The second part consists of qualitative data. This data shows the perceptions of students of online teaching versus hybrid teaching. It compares the differences in participants’ perceptions reported in students’ feedback on the programs during and post-COVID-19. Our results confirm prominent differences exist in the students’ perceptions of their learning experience during the pre-pandemic and post-pandemic periods. The findings of this study suggest that universities need to strive and define a meaning and purpose of international seminars, which enables students to experience a high level of intercultural social interaction face-to-face.
REVIEW | doi:10.20944/preprints202012.0097.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: acute respiratory distress syndrome; mesenchymal stem/stromal cells,; exosome; COVID-19; Clinical trials
Online: 4 December 2020 (10:10:11 CET)
Coronavirus disease 2019 (COVID-19) caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has reached a global epidemic across the world after first reported in Wuhan, China’s Hubei province in December 2019. The pandemic is also associated with acute respiratory distress syndrome (ARDS) characterized by excess inflammation, progressive arterial hypoxemia and dyspnea. Mesenchymal stem/ stromal cells (MSCs) have been investigated as treatment for ARDS due to immunomodulatory property. Exosomes derived from MSCs play an important role in paracrine signaling of MSCs, thereby contributed to immunomodulation of the immune microenvironment. Exosomes are emerged as potential alternative to MSC cell therapy with superiority of safety. In this review, we will introduce MSC-derived exosomes and briefly discuss current progress on MSCs and exosomes in ARDS, which may have clinical implications in pathogenesis and treatment of COVID-19.
ARTICLE | doi:10.20944/preprints201907.0013.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Rett Syndrome; intrinsically disordered region; phylogenetic profile analysis; post-transcriptional modification; methyl-CpG-binding protein 2; cyclin-dependent kinase-like 5; forkhead box protein G1
Online: 1 July 2019 (11:59:56 CEST)
Rett syndrome (RTT) is mainly caused by mutations in methyl CpG-binding protein 2, cyclin-dependent kinase-like 5, or forkhead box protein G1. These RTT-causing proteins harbor an intrinsically disordered region (IDR) whose conformation exhibits spatiotemporal heterogeneity, which not only confer versatility to the protein, but also implicates them in diseases. The IDR generally evolves more rapidly than an ordered structure. In this study, we examined the relationship between pathogenic RTT-associated point mutations in RTT-causing proteins and the evolutionary dynamics of sequence features including structural order–disorder, phosphorylation sites, and evolutionary rates. We also analyzed the molecular properties and evolution of proteins that interact with RTT-causing proteins in terms of phylogenetic profiles, tissue specificity, subcellular localization, expression level, and functions. The results indicate that constrained IDRs may function by forming contacts with other regions in the protein sequence causing pathogenic missense mutations likely to arise in the rapidly evolving IDR and affect molecular networks, leading to disease. The results also provide novel insights into the genetic basis for RTT and the evolution of the neocortex in higher vertebrates.
REVIEW | doi:10.20944/preprints202008.0035.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Experimental radiotherapy; radiobiology; Mesenchymal stem cells; Cell therapy; Exosome; Annexin A1; Acute-respiratory-distress-syndrome; COVID-19
Online: 2 August 2020 (14:54:24 CEST)
Previously we have shown that the combination of radiotherapy with human-umbilical-cord-derived mesenchymal stem-cell therapy significantly reduces the size of the xenotumours in mice, both in the directly irradiated tumour and in the distant non-irradiated tumour or in its metastasis. We have also shown that exosomes secreted from mesenchymal stem-cells pre-irradiated with 2 Gy are quantitatively, functionally and qualitatively different from the exosomes secreted from non-irradiated mesenchymal cells and also that proteins, exosomes and microvesicles secreted by mesenchymal cells suffer a dramatic change when cells are activated or non-activated, with the amount of protein present in the exosomes of the pre-irradiated cells being 1.5-fold times greater compared to those from non-irradiated cells. This finding correlates with a dramatic increase in the anti-tumour activity of the exosomes secreted by pre-irradiated mesenchymal-cells. After the proteomic analysis of the load of the exosomes released from both irradiated and non-irradiated cells, we conclude that annexin A1 is the most important and significant difference between the exosomes released by the cells in either status. Knowing the role of annexin A1 in the control of hypoxia and inflammation which is characteristic of acute-distress-respiratory syndrome, we have designed a hypothetical therapeutic strategy, based on the transplantation of mesenchymal stem cells stimulated with radiation, to alleviate the symptoms of patients who, due to pneumonia caused by COVID-19, require the care of an intensive care unit for patients with life-threatening conditions. With this hypothesis, we would seek to improve the patients’ respiratory capacity and increase the expectations of their cure.
HYPOTHESIS | doi:10.20944/preprints202003.0392.v1
Subject: Biology And Life Sciences, Virology Keywords: COVID-19; diagnosis; comparative genomics
Online: 26 March 2020 (14:58:35 CET)
SARS-CoV 2 also known as COVID-19 is a fast spreading coronavirus related disease that emerged from China in December 2019 and is currently attained the status of a pandemic. There are currently no drugs/ vaccines against the same and moreover limited diagnostic tests to identify the infection. Additionally, these tests are expensive and hence are exclusive for very highly suspected cases of the disease especially in developing countries. This is causing an under-diagnosis which is an alarming state of affairs, as even a single missed SARS-CoV 2 case would spread the disease exponentially and keep it in the community. Through this entirely in silico study, we have developed a cheaper and faster diagnostic method based on simple PCR and restriction enzyme digestion, commonly used in restriction fragment length polymorphism (RFLP) tests. Through comparative genomics, we found the closest neighbours of SARS-CoV 2 then found the highly conserved regions of the genome which were absent in SARS-CoV 1, its closest neighbour. Then we found restriction sites for various enzymes followed by designing of PCR primers flanking those sites. We have found the primer pair to produce a 401 bp amplicon and when digested by SwaI enzyme, it produces two fragments of lengths 216 bp and 185 bp. As an internal control, GAPDH primers are pooled with the SARS-CoV 2 primers as the patient sample will also include human RNA mixed with the viral RNA. This primer pair gives an amplicon of 131 bp and hence a negative sample should show a single band of 131 bp while a positive digested sample will give three bands of 401 bp, 216 bp and 131 bp. The primers are specific to SARS-CoV 2 only and can additionally be used for SYBR green based real time quantification of viral load. The developed tests have not yet been tested in vitro due to stressed out working hours in the only pathogenic virus handling laboratory in our institute. Nonetheless, this study works as a head start for other laboratories to rapidly test the suggested protocols in vitro and make available a cheaper alternative test for SARS-CoV 2 which would especially be beneficial for the lower to middle income countries.
CASE REPORT | doi:10.20944/preprints202009.0009.v1
Subject: Medicine And Pharmacology, Clinical Medicine Keywords: Lyme disease; Post-Treatment Lyme Disease Syndrome (PTLDS); dapsone combination therapy (DDS CT); double dose dapsone combination therapy (DDD CT); babesiosis; persistent infection
Online: 1 September 2020 (11:30:52 CEST)
Three patients with multi-year histories of relapsing and remitting Lyme disease and associated co-infections despite extended antibiotic therapy were each given double dose dapsone combination therapy (DDD CT) for a total of 7-8 weeks. At the completion of therapy, all three patients major Lyme symptoms remained in remission for a period of 25-30 months. In conclusion, Double dose dapsone therapy could represent a novel and effective anti-infective strategy in chronic Lyme disease/PTLDS, especially in those individuals who have failed regular dose dapsone combination therapy (DDS CT) or standard antibiotic protocols. A randomized, blinded, placebo-controlled trial is warranted to evaluate the efficacy of DDD CT in those individuals with chronic Lyme disease/PTLDS.
HYPOTHESIS | doi:10.20944/preprints202208.0398.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: rotavirus; coronavirus; vaccine; SARS-CoV-2; COVID-19; cross immunity; trained immunity; vaccinated breakthrough infections; COVID variants; long-Covid; post-viral syndrome; chronic fatigue; booster
Online: 23 August 2022 (10:50:57 CEST)
This proposal was prepared in the very first weeks of 2020 because of the outbreak of COVID-19.There is good reason to suppose that rotavirus vaccine can be used as protection tool to effectively and safely fight and mitigate SARS-CoV-2 infection and the impact caused by COVID-19 in adult humans, due to the development of cross and trained immunity following rotavirus vaccination. Up-to-date, some rotavirus vaccines are available and approved, two of them have a large experience in results and safety. Little experience has been achieved in the use of rotavirus vaccine in adults. However, it can be expected that it would be safe and effective in adults and in the elderly as well. This proposal explains the background.
ARTICLE | doi:10.20944/preprints202009.0435.v1
Subject: Medicine And Pharmacology, Pediatrics, Perinatology And Child Health Keywords: PIMS; MIS-C; SARS-CoV-2; COVID-19; Kawasaki disease; survey
Online: 18 September 2020 (11:29:49 CEST)
Pediatric inflammatory multisystem syndrome (PIMS) is a new entity in children, likely associated with previous coronavirus disease 19 (COVID-19). Most of reports about PIMS come from countries particularly hit by the COVID-19 pandemic. Our aim was to investigate the nature of inflammatory syndromes in Poland (a country with low COVID-19 prevalence) and to perceive the emergence of PIMS in our country. On May 25th, we have launched a nationwide survey of inflammatory syndromes in children for retrospective (since 4th March 2020) and prospective data collection. Up to 28th July, 39 reported children met inclusion criteria. We stratified them according to age (<5 and ≥ 5 years old) and COVID-19 status. The majority of children had clinical and laboratory features of Kawasaki disease, probably non-associated with COVID-19. However, children ≥5 years of age had PIMS characteristics, and 9 children had COVID-19 confirmation. This is the first to our knowledge report of PIMS register from the country with low COVID-19 prevalence, and it proves that PIMS may emerge in any area involved in the COVID-19 pandemic. In a context of limited COVID-19 testing availability, other risk factors of PIMS, e.g. older age should be considered in the differential diagnosis of inflammatory syndromes in children.
REVIEW | doi:10.20944/preprints202005.0299.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: air pollution; particulate matter; nitrogen dioxide; COVID-19; pandemic
Online: 18 May 2020 (09:36:25 CEST)
A new coronavirus (SARS-CoV-2) have determined a pneumonia outbreak in China (Wuhan and Hubei) on December 2019. While pharmaceutical and non-pharmaceutical intervention strategies are strengthened worldwide, the scientific community has been studying the risk factors associated with SARS-Cov-2, to enrich epidemiological information. For a long time, before the industrialized era, air pollution has been a real and big health concern and it is today a very serious environmental risk for many diseases and anticipated deaths in the world. It has long been known that air pollutants increasing the invasiveness of pathogens for humans by acting as a carrier and making people more sensitive to pathogens through a negative influence on the immune system. Based on scientific evidences, the hypothesis that air pollution, resulting from a combination of factors such as meteorological data, level of industrialization as well as regional topography, can acts both as an infection carrier as a harmful factor of the health outcomes of COVID-19 disease has been raised recently. This hypothesis is turning in scientific evidence, thanks to the numerous studies that have been launched all over the world. With this review, we want to provide a first unique view of all the first epidemiological studies relating the association between air pollution and SARS-CoV-2. Major findings are consistent, highlighting the important contribution of air pollution on the COVID-19 spread and with a less extent also PM10.
ARTICLE | doi:10.20944/preprints202211.0491.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: COVID-19; SARS-CoV-2; exercise; autonomic nervous system; sympathetic nervous system; parasympathetic nervous system; COVID-19 vaccination; post-acute sequelae of COVID-19; communicable diseases
Online: 28 November 2022 (03:39:10 CET)
Coronavirus disease 2019 (COVID-19) has detrimental multi-system consequences. Symptoms may appear during the acute phase of infection, but literature on long-term recovery of young adults after mild-to-moderate infection is lacking. Heart rate variability (HRV) allows observation of autonomic nervous system (ANS) modulation post SARS-CoV-2 infection. Additionally, physical activity (PA) helps improve ANS modulation, where investigation of PA influence on ANS recovery is vital to reduce risk and severity of symptoms. Clinicians may use this research to aid development of non-medication interventions. At baseline, 18 control (CT) and 20 post-COVID-19 (PCOV) participants were observed where general amnamnesis was performed, followed by HRV and PA assessment. 10 CT and 7 PCOV subjects returned for follow-up (FU) evaluation 6 weeks after complete immunization (2 doses) and assessments were repeated. Over the follow-up period, decrease in sympathetic (SNS) activity (mean heart rate: p=0.0024, CI=-24.67- -3.26; SNS index: p=0.0068, CI=-2.50- -0.32) and increase in parasympathetic (PNS) activity (mean RR:p=0.0097, CI=33.72-225.51; PNS index: p=0.0091, CI=-0.20-1.47) were observed. At follow-up, HRV was not different between groups (p>0.05). Additionally, no differences were observed in PA between moments and groups. This study provides evidence of ANS recovery after SARS-CoV-2 insult in young adults over a follow-up period, independent of changes in PA.
ARTICLE | doi:10.20944/preprints202109.0427.v1
Subject: Chemistry And Materials Science, Analytical Chemistry Keywords: Hand sanitizer; COVID-19; alcohol; methanol substitution; gas chromatography; substandard products; falsified products; post-market surveillance
Online: 24 September 2021 (12:25:25 CEST)
The emergence of the COVID-19 pandemic has propelled the use of alcohol-based hand sanitizers to the fore as a SARS-CoV-2 control measure. To be effective these products must comply with relevant quality parameters such as alcohol concentration, methanol limits and purity. The current study was designed to determine the quality of alcohol-based hand sanitizer products in the Nairobi metropolitan area. For this purpose, 74 commercially marketed samples were collected and subjected to analysis by gas chromatography. Only three samples (4.1%) complied with the regulatory specifications for alcohol content, methanol limits and pH. Five samples (6.8%) complied with the specification for alcohol content but did not meet methanol or pH limits. A total of 44 (59.5%) samples had methanol levels that exceeded threshold limits. Eleven samples (14.9%) were found with methanol substitution (i.e., methanol, instead of ethanol or isopropanol, was the main alcohol component). The results show that users of alcohol-based hand sanitizers are being exposed to substandard and falsified products which in addition to being non-efficacious pose harm due to unacceptable levels of toxic impurities. Regular, routine post-market surveillance is needed to prevent such products from reaching the market.
ARTICLE | doi:10.20944/preprints202211.0400.v1
Subject: Medicine And Pharmacology, Orthopedics And Sports Medicine Keywords: Adaptive Force; maximal isometric Adaptive Force; holding capacity; muscle function; Long COVID; post COVID syndrome; muscle weakness; fatigue; neuromuscular control; biomechanical parameter
Online: 22 November 2022 (03:04:41 CET)
Neuromuscular symptoms in long COVID patients are common. Since adequate diagnostics are still missing, investigating muscle function might be beneficial. The holding capacity (maximal isometric Adaptive Force; AFisomax) was previously suggested to be especially vulnerable for impairments. This longitudinal, non-clinical study aimed to investigate the AF in long COVID patients in recovery process. AF parameters of elbow/hip flexors were assessed in 17 patients at three timepoints (pre: long COVID state, post: immediately after first treatment, end: recovery) by an objectified manual muscle test. The tester applied an increasing force on the limb of the patient, who had to resist isometrically for as long as possible. The intensity of 13 common symptoms were queried. At pre, patients started to lengthen their muscles at ~50% of the maximal AF (AFmax), which was then reached during eccentric motion, indicating unstable adaptation. At post and end, AFisomax increased significantly to ~99% and 100% of AFmax, respectively, reflecting stable adaptation. AFmax was statistically similar for all three timepoints. Symptoms intensity decreased significantly from pre to end. In conclusion, maximal holding capacity seems to be impaired in long COVID patients and increases with substantial health improvement. AFisomax might be a suitable sensitive functional parameter to assess long COVID patients and to support therapy process.
ARTICLE | doi:10.20944/preprints202101.0177.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: COVID-19; acute respiratory distress syndrome; methylprednisolone; mechanical ventilation; ventilator-free days; SARS-CoV-2 infection
Online: 11 January 2021 (10:13:42 CET)
Objectives: There are limited data regarding the efficacy of methylprednisolone in patients with acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) requiring invasive mechanical ventilation. We aimed to determine whether methylprednisolone increases the number of ventilator-free days (VFDs) among these patients. Design: Retrospective single-center study Setting: Intensive care unit Patients: All patients with ARDS due to confirmed SARS-CoV-2 infection and requiring invasive mechanical ventilation between 1 March and 29 May 2020 were included Interventions: None Measurements and Main Results: The primary outcome was ventilator-free days (VFDs) during the first 28 days, defined as being alive and free from mechanical ventilation. The primary outcome was analyzed with competing-risks regression based on Fine and Gray’s proportional subhazards model. Death before day 28 was considered to be the competing event. A total of 77 patients met the inclusion criteria. Thirty-two patients (41.6%) received methylprednisolone. The median dose was 1 mg.kg-1 (IQR: 1-1.3 mg.kg-1) and median duration of 5 days (IQR:5-7 days). Patients who received methylprednisolone had a mean 18.8 VFDs (95% CI, 16.6-20.9) during the first 28 days vs. 14.2 VFDs (95% CI, 12.6-16.7) in patients who did not receive methylprednisolone (difference, 4.61; 95% CI, 1.10-8.12; P = 0.001). In the multivariable competing-risks regression analysis and after adjusting for potential confounders (ventilator settings, prone position, organ failure support, severity of the disease, tocilizumab, and inflammatory markers), methylprednisolone was independently associated with a higher number of VFDs (subhazards ratio: 0.10, 95%CI: 0.02-0.45; p=0.003). Hospital mortality did not differ between the two groups (31.2% vs. 28.9%, p=0.82). Hospital length of stay was significantly shorter in the methylprednisolone group (24 days [IQR:15-41 days] vs. 37 days [IQR:23-52 days], p=0.046). The incidence of positive blood cultures was higher in patients who received methylprednisolone (37.5% vs. 17.8%, p=0.052). However, 91% of patients who received methylprednisolone also received tocilizumab. The number of days with hyperglycemia was similar in the two groups. Conclusions: Methylprednisolone was independently associated with increased VFDs and shortened hospital length of stay. The combination of methylprednisolone and tocilizumab was associated with a higher rate of positive blood cultures. Further trials are needed to evaluate the benefits and safety of methylprednisolone in moderate or severe COVID-19 ARDS.
HYPOTHESIS | doi:10.20944/preprints202004.0153.v1
Subject: Biology And Life Sciences, Virology 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/preprints201904.0212.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: stroke; post-stroke dementia; anaemia
Online: 19 April 2019 (09:41:13 CEST)
Background: Whilst lack of concentration is a known symptom of anaemia, its association with post-stroke dementia is unclear. Methods: We used data from a UK regional stroke register. To be eligible, patient must have survived to discharge and had anaemia by WHO criteria. Dementia status and other prevalent co-morbidities were assessed using ICD-10 codes. Patients were followed till May 2015 (mean follow-up 3.7 years, total person years = 27,769). Hazard Ratio for incident dementia was calculated using Cox-proportional hazards model controlling for potential confounders. Fine and Gray model was additionally constructed using mortality as the competing risk. Results: A total of 7,454 stroke patients were included with mean age (SD) of 75.9(12.3) years (50.2% men). Those with anaemia were older, has higher disability and co-morbidity burden prior to stroke. We observed a large amount of variation in the dementia incidence rates over time and that the hazard ratio increased every year. The significant association between anaemia and dementia incidence was lost after controlling for pre-stroke Modified Rankin score (HR1.17(0.97,1.40)). With every 20g/dL increase in Hb was associated with a significant reduction in the risk of dementia after adjustment for age, sex, stroke factors and disability but lost significance after adjustment for vascular risk factors. Competing risk analyses showed similar results. Conclusion: Whilst we found no evidence of anaemia as a risk factor for post-stroke dementia, the findings may be limited by potential under recognition of post stroke dementia.
ARTICLE | doi:10.20944/preprints202206.0206.v1
Subject: Medicine And Pharmacology, Pediatrics, Perinatology And Child Health Keywords: COVID-19; multisystem inflammatory syndrome in children (MIS-C); risk classification; prognosis
Online: 14 June 2022 (11:12:22 CEST)
Background: Two years after the first cases, critical gaps remain in identifying prognostic factors in multisystem inflammatory syndrome in children (MIS-C). Methods: This retrospective study included 99 patients with MIS-C hospitalized between August 2020 and March 2022 in a pediatric tertiary center. The patients were divided into two groups according to clinical severity (low and high-risk). Prognostic values of baseline clinical and laboratory characteristics were evaluated with advanced statistical analysis, including machine learning. Results: Sixty-three patients were male, and the median age was 83 (3–205) months. Fifty-nine patients (%59.6) were low-risk cases. Patients aged six years and over tended to be at higher risk. Involvement of aortic or tricuspid valve or >1 valve was more frequent in the high-risk group. Mortality in previously healthy children was 3.2%. Intensive care unit admission and mortality rate in the high-risk group were 37.5% and 7.5%, respectively. At admission, high-risk patients were more likely to have reduced lymphocyte count and total protein level and increased brain natriuretic peptide (BNP), ferritin, D-dimer, and troponin concentrations. The multiple logistic regression model showed that BNP, total protein, and troponin were associated with higher risk. When the laboratory parameters were used together, BNP, total protein, ferritin, and D-dimer provided the highest contribution to the discrimination of the risk groups (100%, 89.6%, 85.6%, and 55.8%, respectively). Conclusions: Our study widely evaluates and points to some clinical and laboratory parameters that, at admission, may indicate a more severe course. Modeling studies with larger sample groups are strongly needed.
ARTICLE | doi:10.20944/preprints202111.0478.v1
Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome; Long COVID; data acquisition source; post-infectious; longitudinal cohort study; patient-powered
Online: 25 November 2021 (13:51:54 CET)
ME/CFS (Myalgic Encephalomyelitis / Chronic Fatigue Syndrome) is a chronic, complex, heterogeneous disease that affects millions and lacks both diagnostics and treatments. Big data, or the collection of vast quantities of data that can be mined for information, has transformed the understanding of many complex illnesses like cancer (1,2) and multiple sclerosis (3,4), by dissecting heterogeneity, identifying subtypes, and enabling the development of personalized treatments. It is possible that big data can reveal the same for ME/CFS. Solve M.E. developed and launched the You + ME Registry to collect longitudinal health data from people with ME/CFS, people with Long COVID (LC) and control volunteers using rigorous protocols designed to harmonize with other groups collecting data from similar groups of people. The Registry is an invaluable resource because it integrates with a symptom tracking app, as well as a biorepository, to provide a robust and rich dataset that is available to qualified researchers. Accordingly, it facilitates collaboration that may ultimately uncover causes and help accelerate the development of therapies.
ARTICLE | doi:10.20944/preprints202106.0362.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: COVID-19; depression; chronic fatigue syndrome; inflammation; neuro-immune; psychiatry
Online: 14 June 2021 (13:01:31 CEST)
Background: COVID-19 is associated with neuropsychiatric symptoms including increased depressive, anxiety and chronic fatigue-syndrome (CFS)-like physiosomatic (previously known as psychosomatic) symptoms.Aims: To delineate the associations between affective and CFS-like symptoms in COVID-19 and chest CT-scan anomalies (CCTAs), oxygen saturation (SpO2), interleukin (IL)-6, IL-10, C-Reactive Protein (CRP), albumin, calcium, magnesium, soluble angiotensin converting enzyme (ACE2) and soluble advanced glycation products (sRAGEs).Method: The above biomarkers were assessed in 60 COVID-19 patients and 30 heathy controls who had measurements of the Hamilton Depression (HDRS) and Anxiety (HAM-A) and the Fibromyalgia and Chronic Fatigue (FF) Rating Scales. Results: Partial Least Squares-SEM analysis showed that reliable latent vectors could be extracted from a) key depressive and anxiety and physiosomatic symptoms (the physio-affective or PA-core), b) IL-6, IL-10, CRP, albumin, calcium, and sRAGEs (the immune response core); and c) different CCTAs (including ground glass opacities, consolidation, and crazy paving) and lowered SpO2% (lung lesions). PLS showed that 70.0% of the variance in the PA-core was explained by the regression on the immune response and lung lesions latent vectors. Moreover, one common “infection-immune-inflammatory (III) core” underpins pneumonia-associated CCTAs, lowered SpO2 and immune activation, and this III core explains 70% of the variance in the PA core, and a relevant part of the variance in melancholia, insomnia, and neurocognitive symptoms.Discussion: Acute SARS-CoV-2 infection is accompanied by lung lesions and lowered SpO2 which both may cause activated immune-inflammatory pathways, which mediate the effects of the former on the PA-core and other neuropsychiatric symptoms due to SARS-CoV-2 infection.
CASE REPORT | doi:10.20944/preprints202103.0680.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Acute febrile illness; Alphavirus; chikungunya virus; post-chikungunya musculoskeletal disorder; post-chikungunya chronic inflammatory rheumatism
Online: 29 March 2021 (10:56:13 CEST)
Chikungunya virus is a re-emerging mosquito-borne alphavirus. Outbreaks are unpredictable and explosive in nature. Fever, arthralgia, and rash are common symptoms during the acute phase. Diagnostic tests are required to differentiate chikungunya virus from other co-circulating arboviruses, as symptoms can overlap, causing a dilemma for clinicians. Arthritis is observed during the sub-acute and chronic phases, which can flare up, resulting in increased morbidity that adversely affects activities of daily living. During the 2019 chikungunya epidemic in Thailand, cases surged in Bangkok in the last quarter of the year. Here, we demonstrate the chronic sequelae of post-chikungunya arthritis in one of our patients 1 year after the initial infection. An inflammatory process involving edema, erythema, and tenderness to palpation of her fingers' flexor surfaces was observed, with positive chikungunya IgG and negative IgM tests and antigen. The condition produced stiffness in the patient’s fingers and limited their range of motion, adversely affecting daily living activities. Resolution of symptoms was observed with a short course of an anti-inflammatory agent. More research is required to determine whether sanctuaries enable chikungunya virus to evade the host immune response and remain latent, flaring up months later and triggering an inflammatory response that causes post-chikungunya arthritis.
REVIEW | doi:10.20944/preprints202207.0154.v1
Subject: Social Sciences, Behavior Sciences Keywords: post-stroke aphasia; pharmacotherapy; cholinergic treatment
Online: 11 July 2022 (08:58:05 CEST)
Despite the relative scarcity of studies focusing on pharmacotherapy in aphasia, there is evidence in the literature indicating that remediation of language disorders via pharmaceutical agents could be a promising aphasia treatment option. Among the various agents used to treat chronic aphasic deficits, cholinergic drugs have provided interesting results. In the current review, we focused on published reports investigating the impact of acetylcholine on language and further cognitive disturbances. It has been suggested that acetylcholine plays an important role in neuroplasticity and is related to several aspects of cognition, such as memory and attention. Moreover, cholinergic input is diffused to a wide network of cortical areas, which have been associated with language sub-processes. This could be a possible explanation for the positive reported outcomes of cholinergic drugs in aphasia recovery, and specifically in distinct language processes, such as naming and comprehension, as well as overall communication competence. However, evidence with regard to functional alterations in specific brain areas after pharmacotherapy is rather limited. Finally, despite the positive results derived from the relevant studies, cholinergic pharmacotherapy treatment in post-stroke aphasia has not been widely implemented. The present review aims to provide an overview of the existing literature in cholinergic pharmacotherapy interventions in post-stroke aphasia, following an integrated approach by converging evidence from neuroanatomy, neurophysiology, and neuropsychology.
REVIEW | doi:10.20944/preprints202109.0359.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: p53; post-translational modifications; alzheimer's disease
Online: 21 September 2021 (12:01:29 CEST)
Our understanding of Alzheimer’s disease (AD) pathogenesis has developed with several hypotheses over the last 40 years, including the Amyloid and Tau hypotheses, respectively. More recently, the p53 protein, well-known as ‘the guardian of the genome,’ has gained attention for its role in the early evolution of AD. This is due to p53’s central role in the control of oxidative stress and potential involvement in both Amyloid and Tau pathways. p53 is commonly regulated by post-translational modifications (PTMs), which affect its conformation, increasing its capacity to adopt multiple structural and functional states, including those that can influence several processes in AD. The following review will explore the impact of p53 post-translational modifications (PTMs) on its function and consequential involvement in AD pathogenesis.
ARTICLE | doi:10.20944/preprints202104.0694.v1
Subject: Social Sciences, Psychology Keywords: Causes, post traumatic stress disorder,refugees
Online: 26 April 2021 (20:51:27 CEST)
Abstract Objectives To assess the causes and risk factors of posttraumatic stress disorder (PTSD) in adult asylum seekers and refugees. To explore whether the causes and risk factors of PTSD, between male and female adult refugees/ asylum seekers is different. Study design Systematic review of current literature. Data Sources PubMed, Web of Science, Scopus and Google Scholar up until February 2019 Method A structured systematic search was conducted in the relevant databases. Papers were excluded, if they failed to meet the inclusion and exclusion criteria. Afterwards, a qualitative assessment was performed on the selected papers. Results 12 Studies were included for the final analysis. All papers were either case studies/report or cross sectional studies. The number of traumatic events experienced by refugees/asylum seekers, is the most frequently reported pre-migration causes for PTSD development. Whilst acculturative stress, is the most common post migration stressor. There were mixed reports, regarding the causes of PTSD between both genders of refugees/asylum seekers. Conclusion This reviews’ findings, have potential clinical application into helping clinicians, to risk stratify refugees/asylum seekers for PTSD development and thus aid in embarking on earlier intervention measures. However, more rigorous research similar to this one, is needed for it to be implemented into clinical practice.
TECHNICAL NOTE | doi:10.20944/preprints202012.0300.v1
Subject: Computer Science And Mathematics, Computer Science Keywords: Post Quantum Cryptography, Oil and Vinegar
Online: 13 December 2020 (21:31:13 CET)
Public key encryption methods are often used to create a digital signature, and where Bob has a public key and a private key. In order to prove his identity, he will encrypt something related to the message with his private key, and which can then be checked with his public key. The main current methods of public-key encryption include RSA and ECC (Elliptic Curve Cryptography), and which involve computationally difficult operations. But these operations have not been proven to be hard in an era of quantum computers. One well-known hard problem is the solving of quadratic equations with $m$ equations with $n$ variables. This is a known NP-hard problem, even in a world of quantum computers. These can be used as post-quantum signature schemes and which involve multivariate equations. In order to understand these methods, this paper outlines a simple example of implementing the oil and vinegar method, and where we have a number of unknown oil variables and a number of known vinegar variables, and where the vinegar variables help convert the hard problem into an easy one.
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: spontaneous; racemization; apoptosis; post translational modification
Online: 18 November 2020 (11:09:30 CET)
Biochirality is evident in the hierarchical relation of molecular and cellular physiology during organism development and aging. Chirality influences the higher levels of biological processes, such as perception, memory and cognition, through intermolecular interactions between DNA, proteins, and lipids. At the molecular level, an organism's aging is the accumulation of macro-molecules with the aberrant composition, chirality, and folding. Cellular aging is driven by the non-physiological phase transitions (PhTs) withing membrane-bound and membrane-less compartments. Genomic instability and protein aging, as the interconnected root-causes of cell and organism aging, share two essential feature – spontaneous nature and accumulation over a lifetime. Consequently, we will analyze the interaction between the enzymatic (Enz) and spontaneous (Sp) post-translational modifications (PTMsEnz and PTMs Sp). Both forms of PTMs significantly contribute to the balance of L- and D-amino acids (L/D-AAs) in organisms, modulating the functions of nervous and immune systems. The most abundant form of PTM - enzymatic phosphorylation is bio-chemically associated with the spontaneous racemization (RzSp). The crass talk of enzymatic phosphorylation and spontaneous racemization, as an essential determinant of protein aging and aggregation, associated with the aberrant autophagy, apoptosis, and cell signaling, is discussed in this review.
ARTICLE | doi:10.20944/preprints202302.0214.v1
Subject: Business, Economics And Management, Economics Keywords: Post-harvest losses; Avocado; producer’s; Quantity; MLR
Online: 13 February 2023 (10:00:45 CET)
Current study was to estimation the post-harvest loss of avocado at the producer level using cross-sectional data obtained from 385 proportionately sampled respondents from Wolaita and Kembata Tembaro Zones, the SNNPR of Ethiopia. Descriptive and multiple regression analysis were used to the amount and determinant of post harvest loss of avocado fruits. Estimated total post harvest- loss of avocados was 24%; of which 5.7% unacceptable harvesting methods and 4.9% of improper storage practices. The respondent's sex, education, income, training, contact with extension agents, distance from the nearest road, and off-farm income were found to be negative determinants, whereas storage accessibility and avocado harvest techniques were found to be positive determinants of post-harvest loss of avocado fruits. Post-harvest management techniques for avocados need to be better understood and used by avocado growers if they are to minimize losses. Post-harvest losses contribute considerably to food insecurity and create a problem for the source of revenue for people and the economy of the country as well. Therefore, the use of a practical and effective post-harvest loss reduction technique could be a sustainable solution to increase food availability, eliminate hunger and improve farmers' livelihoods.
REVIEW | doi:10.20944/preprints202107.0623.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: spontaneous post-translational modification, racemization, glycation, glycosylation.
Online: 28 July 2021 (10:35:48 CEST)
The universal chirality is the commonly accepted view of nature. Biological chirality is the distinct part of the more general phenomena. Following this view, all living organisms are characterized by the non-equilibrium state of their molecular constituents. From the thermodynamic perspective, the non-equilibrium state of biomolecular ensemble holds inevitable consequences being the substrate of spontaneous reactions directed to equilibrium (not associated with life) state. At the protein level, spontaneous biological reactions represent the natural part of proteins' post-translational modifications (PTMs). The essential contribution to the origin and maintenance of the non-equilibrium state belongs to prevalent bio-molecular chirality. Correspondently, spontaneous PTMs such as racemization and glycation, working against life-supporting prevalent chirality, are known as the significant determinants of protein misfolding, dysfunctions, and aggregation. Accumulation of aberrant protein during life-span allows consideration of time-dependent spontaneous racemization and glycation as protein aging. Spontaneous PTMs of proteins is occurring in the interaction with other forms of enzymatic and non-enzymatic PTMs. In this review, we are considering the contribution of spontaneous racemization and non-enzymatic glycosylation to protein aging.
ARTICLE | doi:10.20944/preprints202001.0150.v1
Subject: Public Health And Healthcare, Public, Environmental And Occupational Health Keywords: maternal smoking; post partum smoking; health education
Online: 15 January 2020 (12:15:54 CET)
Smoking during pregnancy remains one of the most significant risk factors for poor birth outcomes. The Loma Linda University Health Comprehensive Tobacco Treatment Program (CTTP) is the largest maternal tobacco cessation program in San Bernardino County – the largest county in the contiguous US. CTTP is an eight week, incentivized, behavioral intervention for tobacco cessation for pregnant smokers. As part of program evaluation, we used a retrospective cohort design to assess smoking abstinence and to identify predictors of relapse/smoking after enrollment. Among CTTP cohort enrollees (n=233) from 2012-2013 we found: 1) a 28.4% 8 week point prevalence abstinence (PPA), and at a median of 9 months of follow-up after the PPA, 81.6% continued to indicate tobacco cessation, and 2) a high rate of relapse or loss to follow-up (56%). Our modeling of relapse/smoking after enrollment indicated that this was higher in young mothers, non-Hispanic mothers (White, Black), first/third trimester mothers, and rural mothers. The evaluation identified efficacy of the behavioral model at 8 weeks, but that relapse/smoking was occurring in disparity populations. Formative research is needed to expand the programmatic outreach and enrollment of mothers wanting to quit smoking.
ARTICLE | doi:10.20944/preprints201912.0413.v1
Subject: Social Sciences, Psychology Keywords: infant cry; post-partum depression; acoustic analysis
Online: 31 December 2019 (15:55:20 CET)
Postpartum depression (PPD), a condition that affects up to the 15% of mothers in high-income countries, reduces attention toward the needs of the child and it is among the first causes of infanticide. PPD is usually identified using self-report measures and therefore the diagnosis may not always be valid. Previous studies highlighted the presence of significant differences in the acoustical properties of the vocalizations of children of depressed and healthy mothers. In this study, cry episodes of infants of depressed and non-depressed mothers are analyzed to investigate the possibility that a machine learning model can identify PPD in mothers from the acoustical properties of infants' vocalizations. Acoustic features (F0, F1-4, Intensity) are first extracted from recordings of crying infants, then novel cloud-based artificial intelligence models are employed to identify maternal depression versus non depression from estimated features. Trained model shows that commonly adopted acoustical features can be successfully used to individuate Post-Partum Depressed mothers with very high accuracy (89.5%).
ARTICLE | doi:10.20944/preprints201801.0108.v1
Subject: Medicine And Pharmacology, Pharmacy Keywords: paracetamol; breastfeeding; post; childhood; prophylactic; immunization; vaccination
Online: 12 January 2018 (07:09:16 CET)
Background: Paracetamol may be use as antipyretic agent for the treatment of fever, as well as an analgesic in the treatment of mild to moderate pain on post vaccination in infants. The use of Paracetamol during fever may be or may not be recommended since it may alter natural human body immune response although it may reduce pain. Objectives: This study described the relevancy of Paracetamol use post infants vaccination based on data collection systematic review analyses. This study aims to describe the effectiveness of breastfeeding in reducing pain and Paracetamol in reducing fever and pain post infants vaccination. Data Sources and Study Selection: Electronic literature search by hand searching six (6) databases which include Ovid LWW Total Access Collection and Medline, CINAHL (Cumulative Index to Nursing and Alled Health Literature) Plus with Fulltext, Science Direct, Proquest Dissertations and Theses, Proquest Education Journal and Proquest Health and Medical Complete. Additionally, manual reference checks of all articles on Paracetamol and breastfeeding post infants vaccination published in English Language between 1978 and 2017. Two level of screening were used on 9614 citations which include screening of abstracts and titles followed by full text screening. Data Synthesis: Data synthesis were tabulated into study characteristics, quality and effects. Authors of trials were not contacted for further details or provision of original data if the published report contained insufficient information. The study findings, as reported by the authors, were included in this review. The data in this research cannot be pool due to not enough data regarding odd ratio or relative risk as well as confidence interval in each study. Results: Systematic review of breastfeeding included three (3) studies from 9614 of database searching. The reviews of all these three (3) studies found significant benefit from breastfed in pain score and duration of crying as well as behavioral changes. None study stated the unbeneficial of breastfeeding before, during and after immunization. Meanwhile, systematic review of Paracetamol effectiveness included four (4) studies from 1177 of database searching. The reviews of two (2) studies found significant benefit from prophylaxis Paracetamol in fever and only one (1) study found significant benefit from prophylaxis Paracetamol in fussiness. On the other hand, there was one (1) study found not signifiant benefit from prophylaxis Paracetamol in fever. Other than that, there were two (2) studies evaluate the safety of prophylactic Paracetamol which revealed different outcomes, in which study by Prymula et. al. in 2009 found that antibody responses to several antigens were reduced significantly, and the other study by Uhari et. al. in 1988 found that antibody titres to DTP bacteria of placebo and PCM not differ significantly. Thus, Paracetamol seems to be not relevant post infants vaccination and breastfeeding was found to be beneficial post infants vaccination. Conclusions: The relevancy of giving Paracetamol post all types of vaccination may be questionable since the safety issue of this intervention may be arised. Breastfeeding before, during and after immunization are recommended for pain reduction as it was proved effectively. Finally, in deciding Paracetamol to be of rational use following infants immunization, it may need for further research which include in depth quantitative and qualitative studies to identify specific problem and causes regarding this issue.
ARTICLE | doi:10.20944/preprints202305.1535.v1
Subject: Public Health And Healthcare, Public Health And Health Services Keywords: IBD; GERD; Mental-health; POST-SARS-CoV2-symdromes
Online: 23 May 2023 (02:37:42 CEST)
Abstract: Gastroesophageal reflux disease (GERD), the inflammatory bowel disease (IBD), and mental health issues are significant public health concerns in globally. Although rising peaks observed post-COVID-19, there is a sever paucity in high quality data. Using descriptive analysis, we identified the frequency and associations of age- and gender, sport, genetic, and psychiatric consequences in the coexistence of GERD and IBD in 2067 participants 18 to >60 years with mean age of 26.8 ± 12.9 years. Most were 18 -29 years old (66%, n=1364) of which majority were young Saudi females (72.4%, n=1496). Estimated 1099 (53.2%) were students, 428 (20.7%) were unemployed, and 540 (26.1%) were. The majority were Saudis (94.7%, n= 1957). Psychological syndromes anxiety (60.7%), stress (60.7%), and depression (60.6%) were most frequent; whereas, IBD (48.7%) and GERD (36.3%), respectively were the second and third. In 51 % respondents depression, anxiety, and stress occurred first while in 33.9%, and 24.3% IBD and GERD, respectively, were the first signs. In most respondents (59.2%, n=1178), these signs first appeared recently and 33.6% (n=669) reported occurrence during adult life, and only in 7.2% (n=144) the signs noticed during childhood (7.2%, n=144)). Aggravating factors were 32.9% (n=681) genetic and other factors of which 476 (69.9%) inherited IBD while 215(31.6%) and 175 ((25.7), respectively, inherited psychological (depression, anxiety, and stress) and GERD. However, only 18.3% sought treatment (n=378) and only 66 (3.2%) had colectomy or a colostomy bag. Little over half of the studied population (58.1%, n=1201) were active in outdoor. GERD or IBS and psychological factors (anxiety, depression, and stress), were significantly associated with age (P value =.001).; GERD with old age, IBD with mid-age 40-49 years, and psychological disorders among younger ages. Thus, while mental health issues predispose young millennial women to neurogastroenterological disorders, the IBD and GERD initiate psychological problems in old and mid-ages, respectively. Intriguingly, despite the significantly mosaic global genetic population structures, their lifestyles, and nutritional habits, the pattern of these disorders remains similar. Thus, this is potentially consistent with notion that the gut nerve cells are conserved and that the changes in gut dysbiosis of gut microbiome signatures are responsible. These findings have significant clinical implications in the patient treatment strategies and tailored educational and awareness programs in lifestyle medicine. Future microbiome studies would reveal more insight into the mechanisms of disorders.
ARTICLE | doi:10.20944/preprints202305.0515.v1
Subject: Computer Science And Mathematics, Security Systems Keywords: Quantum Computing; Lattice-based cryptosystems; Post-Quantum Cryptography
Online: 8 May 2023 (10:27:49 CEST)
The rapid development of quantum computing devices promises powerful machines with capabilities that solve a wide range of problems that traditional computers cannot. Therefore, quantum computers generate new threats at unprecedented speed and scale and specifically pose an enormous threat to encryption. Lattice-based cryptography is considered to be the rival to a quantum computer attack and the future of post-quantum cryptography. So, cryptographic protocols based on lattices have a variety of benefits, like security, efficiency, lower energy consumption, and speed. In this work, we study the most well-known lattice-based cryptosystems while a systematic evaluation and comparison is presented also, and focuses on their strengths and weaknesses.
ARTICLE | doi:10.20944/preprints202303.0173.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Vibrio; Oysters; Post-harvest; Modelling; Temperature; Ice-treatment
Online: 9 March 2023 (09:40:44 CET)
Temperature is a critical factor that influences the proliferation of pathogens in hosts. The impact of temperature on pathogens is commonly explored in controlled and constant temperatures. Experiments under varying environmental temperature are becoming more frequent, however, testing every temperature scenario à la carte is unachievable. One example of this is the human pathogen Vibrio parahaemolyticus (Vp) in oysters. Here, a predictive model was developed for predicting the growth of Vp in oysters under varying ambient temperature. The model was fitted and evaluated against data from experiments studying growth and inactivation of Vp in oysters at eight constant temperatures. Once evaluated, Vp dynamics in oysters were estimated at different post-harvest varying temperature scenarios affected by water and air temperature, and different ice treatment timing. The model performed adequately under varying temperature, reflecting that (i) increasing temperature, particularly in hot summers, favors a rapid Vp growth in oysters, resulting in a very high risk of gastroenteritis in humans after consumption of a serving of raw oysters, (ii) pathogen inactivation due to day/night oscillations, and more evidently, due to ice treatments, (iii) ice treatment is much more effective limiting risk of illness when applied immediately onboard compared to dockside. The model results to be a promising tool for improving the understanding of the Vp-oyster system and support studies on public health impact of pathogenic Vp associated with raw oyster consumption. Although robust validation of the model predictions is needed, initial results and evaluation show the potential of the model to be easily modified to match similar systems where the temperature is a critical factor shaping the proliferation of pathogens in hosts.
ARTICLE | doi:10.20944/preprints202303.0093.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: septicemia; septic shock; post-sepsis syndrome; cytokines; inflammation
Online: 6 March 2023 (06:43:46 CET)
Sepsis is a life-threatening condition with high hospital mortality. Elevated mortality has also been observed in patients after hospital discharge due to post-sepsis syndrome (PSS). The etiology of PSS is still not entirely known, but it involves inflammation. Plasma extracellular vesicles (EVs) are recognized as a unique mechanism of intercellular communication in inflammatory processes. It has been reported that EV microRNA (miRNA) production during the acute sepsis phase may persist until after disease resolution and is associated with PSS. We employed mass spectrometry and qPCR analysis to determine the protein and miRNA composition of plasma-derived EVs of 36 patients during sepsis-related hospitalization, immediately after ICU discharge (post-sepsis), and three, six, twelve, and up to 36 months post-sepsis. We determined that patients’ immune system cells were the primary EV source. Fifteen differentially expressed EV miRNAs (DEmiRs) were identified in samples from septic patients compared to the control group. Predictive analyses revealed that these DEmiRs could influence inflammation by modulating pathways mediated by NF-κB, STAT3, and TLR4 signaling activation. Thirteen miRNAs (-15b-5p,-16-5p,-20a-5p,-25-3p,-27a-3p,-29a-3p,-30d-5p,-93-5p,-146a-5p,-148a-3p,-191-5p,-195-5p,-223-3p) were downregulated in the death group compared to the survivor group, making them candidate prognostic markers of ICU survival. One year after ICU discharge, the expression of miR-21-5p and miR-195-5p were decreased in the survivor group. The miRNAs identified in the present study represent potential biomarkers for the survival prognosis of post-sepsis patients.
ARTICLE | doi:10.20944/preprints202108.0571.v1
Subject: Biology And Life Sciences, Plant Sciences Keywords: Arabidopsis thaliana; plastid; co-maturation; post-transcriptional; Nanopore
Online: 31 August 2021 (11:48:48 CEST)
Plastid gene expression involves many post-transcriptional maturation steps resulting in a complex transcriptome composed of multiple isoforms. Although short read RNA-seq has considerably improved our understanding of the molecular mechanisms controlling these processes, it is unable to sequence full-length transcripts. This information is however crucial when it comes to understand the interplay between the various steps of plastid gene expression. Here, the study of the Arabidopsis leaf plastid transcriptome using Nanopore sequencing showed that many splicing and editing events were not independent but co-occurring. For a given transcript, maturation events also appeared to be chronologically ordered with splicing happening after most sites are edited.
CASE REPORT | doi:10.20944/preprints202105.0220.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Post-cardiac injury syndrome; pericarditis; percutaneous coronary intervention.
Online: 10 May 2021 (15:48:46 CEST)
Background: Percutaneous coronary intervention (PCI) is known as a very rare possible trigger of pericarditis. Most frequently it develops after a latent period or early in case of periprocedural complications. In this report, we present an atypical early onset of pericarditis after the uncomplicated PCI. Case Summary: A 58-year-old man was admitted to the hospital for the PCI of the chronic total occlusion of left anterior descending (LAD) artery. An initial electrocardiogram (ECG) was unremarkable. PCI attempt was unsuccessful. There were no procedure related complications observed at the end of PCI attempt and patient was symptom free. Six hours after interventional procedure the patient complained of severe chest pain. The ECG demonstrated ST-segment elevation in anterior and lateral leads. Troponin I was mildly elevated but coronary angiogram did not reveal impairment of collateral blood flow to the LAD territory. Because of pericarditic chest pain, typical ECG findings and pericardial effusion with elevated C-reactive protein, the diagnosis of acute pericarditis was established, and a course of nonsteroidal anti-inflammatory drugs (NSAIDs) was initiated. Chest pain was relieved and ST-segment elevation almost completely returned to baseline after three days of treatment. The patient was discharged in stable condition without chest pain on the fourth day after symptom onset. Conclusions: Acute pericarditis is a rare complication of PCI. Despite the lack of specific clinical manifestation, post-traumatic pericarditis should be considered in patients with symptoms and signs of pericarditis and a prior history of iatrogenic injury or thoracic trauma.
REVIEW | doi:10.20944/preprints202007.0107.v1
Subject: Chemistry And Materials Science, Electronic, Optical And Magnetic Materials Keywords: Magnetic microwires; post-processing; hysteresis loops; magnetic anisotropy
Online: 7 July 2020 (02:41:20 CEST)
The influence of post-processing conditions on the magnetic properties of amorphous and nanocrystalline microwires have been thoroughly analyzed, paying attention on the influence of magnetoelastic, induced and magnetocrystalline anisotropies on the hysteresis loops of Fe-, Ni- and Co-rich microwires. We showed that magnetic properties of glass-coated microwires can be tuned by the selection of appropriate chemical composition and geometry in as-prepared state or further considerably modified by appropriate post-processing, which consists of either annealing or glass-coated removal. Furthermore, stress-annealing or Joule heating can further effectively modify the magnetic properties of amorphous magnetic microwires owing to induced magnetic anisotropy. Devitrification of microwires can be useful for either magnetic softening or magnetic hardening of the microwires. Depending on the chemical composition of the metallic nucleus and on structural features (grain size, precipitating phases) nanocrystalline microwires can exhibit either soft magnetic properties or semi-hard magnetic properties. We demonstrated that the microwires with coercivities from 1 A/m to 40 kA/m can be prepared.
ARTICLE | doi:10.20944/preprints201910.0131.v1
Subject: Biology And Life Sciences, Horticulture Keywords: Morus sp.; cellulose; cymbopogon citratus; Post harvest quality
Online: 11 October 2019 (06:10:14 CEST)
Blackberry is a fruit that has high nutritional value, a factor that has expanded its consumption worldwide. However, due to the fragility of the fruits and the high incidence of postharvest diseases, the fruits have a short shelf life. Thus, the objective of this study was to evaluate whether the application of coatings based on microfibrillated cellulose (NC) and lemongrass essential oil (EO) nanoparticles can prolong the shelf life of blackberry fruits after harvest. EO-coated blackberry fruits at nanocellulose concentrations were analyzed as follows: 0; 0.2; 0.4; 0.6 and 0.8%, in addition to the control treatment of which neither essential oil nor nanocellulose was used, for each treatment five repetitions were used. The fruits were analyzed soon after the application of the cover and at three and six days after storage. Fruit quality was assessed by soluble solids (SS), titratable acidity (TA), pH, fresh weight loss (FWL) and colorimetric parameters such as luminosity, hue angle and fruit peel chroma. Coating on EO (1000 ppm) blackberries combined with NC at concentrations of 0.2, 0.4 and 0.6% is promising in preserving blackberry fruits and reducing the process color reversal, up to six days of storage. The 0.4% NC + 1000 ppm EO conjugated coating showed no SS changes in blackberry fruits during the six days of storage.
ARTICLE | doi:10.20944/preprints201904.0132.v1
Subject: Biology And Life Sciences, Agricultural Science And Agronomy Keywords: rachis; traditional; post shooting approach; economic production; demand
Online: 11 April 2019 (05:41:39 CEST)
Background and Objectives: Due to huge demand and availability of Banana, innovative cost effective method is necessary to promote and smoothen the banana production among farmers commercially mitigating the demand. Method and Materials: In this study, we feed cow dung mixture along with Urea, TSP, MoP, water to the distal part of rachis after cutting down male bud as soon as the female flowers matured into fruits (T1). The effect of this method was then compared with two control groups; one with the same strategy except fertilizer applied on root following ring method (C1, Positive control) and another was male flower untouched without applying fertilizer on rachis or root (C2, Negative control). Results and Conclusion: T1 showed more than double increase in length than controls. In the same way, in case of shape (diameter), T1 (0.46 cm) showed twice as better growth in the C1 (0.22 cm) and C2 (0.18 cm). Trend analysis showed the test group T1 curve is much steeper than the control groups suggesting faster growth rate than the other two. Finally, the cost of fertilizers for T1 per plant was estimated 0.091 USD while for positive control C1 it was 2.9 USD. This study shows an approach to be effective and economic comparing to traditional method of fertilizer application, which can be adapted as a new method of banana production.
REVIEW | doi:10.20944/preprints201701.0122.v1
Subject: Chemistry And Materials Science, Organic Chemistry Keywords: multicomponent reaction; MCR; post condensation modification PCM; post condensation cyclisation PCC; MFCR; multifunction catalysis; variability; diversity; complexity; efficiency of synthesis
Online: 26 January 2017 (10:04:55 CET)
Synergistic effects between reactions, reagents and catalysts can lead to minor heats of reaction and occur as an inherent result of multi-component reactions (MCRs) and their extensions. They enable syntheses to be performed at a low energy level and the number of synthesis steps to be drastically reduced in comparison with ‘classical’ two-component reactions. The very high potential for variability, diversity and complexity of MCRs additionally generates an extremely diverse range of products, thus bringing us closer to the aim of being able to produce tailor-made and extremely low-priced materials, drugs and libraries.
ARTICLE | doi:10.20944/preprints202106.0248.v1
Subject: Chemistry And Materials Science, Food Chemistry Keywords: post-harvest; grape; wine; withering; stilbenes; aroma; Amarone; Corvina
Online: 9 June 2021 (09:03:25 CEST)
In the Valpolicella area (Verona - Italy) Vitis vinifera cv. Corvina is the main grape variety used to produce Amarone wine. Before starting the winemaking process, the Corvina grapes are stored in a withering (i.e., dehydrating) warehouse until about 30% of the berry weight is lost (WL). This practice is followed to have the chemical metabolites concentrate in the berry and enrich the Amarone wine in aroma and antioxidant compounds. In compliance with the guidelines and strict Amarone protocol set by the Consorzio of Amarone-Valpolicella, withering must be carried out by setting the grapes in a suitable environment, either under controlled relative air humidity (RH) conditions and wind speed (WS) – no temperature modification is to be applied – or, following the traditional methods, in open-air natural environmental conditions. In general, the two processes have different dehydration kinetics due to the different conditions in terms of temperature, RH, and WS, which affect the accumulation of sugars and organic acids and the biosynthesis of sec-ondary metabolites such as stilbenes and glycoside aroma precursors. For this study, the two grape-withering processes were carried out under controlled (C) and not-controlled (NC) condi-tions and the final compositions of the Corvina dried grapes were compared also to evaluate the effects on the organoleptic characteristics of Amarone wine. The findings highlighted differences between the two processes mainly in terms of the secondary metabolites of the dried grapes, which affect the organoleptic characteristics of Amarone wine.
ARTICLE | doi:10.20944/preprints202105.0153.v1
Subject: Arts And Humanities, Religious Studies Keywords: Shoah, Christology, post-Shoah Christology, religious pluralism, witness, genocide
Online: 10 May 2021 (09:50:57 CEST)
Post-Shoah Christology is embedded in the unique relationship of Jews and Christians, especially Jesus’ Jewishness and the Jewish roots of Christianity, as well as Christian moral failures towards Jews before and during the Shoah. Essential for contemporary Christianity, a vibrant post-Shoah Christology confronts three main challenges, each demanding a different response. The first challenge is the reality that soon there will be no more first-generation witnesses to the Final Solution. Such is an inevitable challenge that has to be faced and prepared for. Religious pluralism is the second challenge, and includes a number of related threads, yet should ultimately be embraced. The third challenge is the (inevitable?) loss of memory, passion, and urgency, a willful forgetfulness by Christians towards the importance of the Jewish-Christian relationship, and especially, Christian failure in the Shoah. This challenge demands robust refutation and ongoing struggle. Before addressing these challenges, I will first further define and highlight the need for a post-Shoah Christology and will conclude this article with three general and three concrete hopes for a viable post-Shoah Christology.
Subject: Chemistry And Materials Science, Analytical Chemistry Keywords: Azolium MOFs; Dye adsorption; Post modification; Cross-coupling reactions
Online: 30 November 2020 (14:14:52 CET)
Two ligands, 1, 3-bis(4-carboxyphenyl)imidazolium chloride and 4, 4՛-bipyridine, were employed to prepare nickel and zinc azolium based MOFs, 1 and 2 by the mixed ligand solvothermal approach. The positively charged azolium moieties in the imidazolium linker resulted in a charged environment in the as-synthesized frameworks. As a result, 1 and 2 demonstrated preferential adsorption of CO2 over methane molecules in the gas phase adsorption due to the higher quadruple moment of CO2, which interacts more with the positively charged frameworks. Besides, in aqueous media, 1 and 2 exhibited incredible adsorption efficiency for anionic dyes. In the following, MOF 1 was metallated at the carbene site of the azolium linker to generate the novel heterogeneous catalyst 1-Pd, which was successfully applied for Sonogashira and Suzuki-Miyaura coupling reactions without losing its activity after three cycles.
ARTICLE | doi:10.20944/preprints202011.0240.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Post-mortem Cardiac magnetic resonance; hypertrophic cardiomyopathy; sudden death
Online: 6 November 2020 (10:44:52 CET)
Post-mortem cardiac magnetic resonance (PMCMR) is an emerging tool supporting forensic medicine for the identification of the causes of cardiac death, as hypertrophic cardiomyopathy (HCM). We proposed a new method of PMCMR to diagnose HCM despite myocardial rigor mortis. Methods: we performed CMR in 49 HCM patients, 30 non-HCM hypertrophy and 32 healthy controls. In cine images, rigor mortis was simulated by the analysis of the cardiac phase corresponding to the 25% of diastole. Left ventricular mass, mean and standard deviation (SD) of WT, maximal WT, minimal WT and their difference, were compared for the identification of HCM. These parameters were validated at PMCMR, evaluating 8 hearts with HCM, 10 with coronary artery disease and 10 with non-cardiac death. Results: The SD of WT with a cut-off of > 2.4 had the highest accuracy to identify HCM (AUC 0.95, 95%CI 0.89-0.98). This was particularly evident in female population of HCM (AUC=0.998), with 100% specificity (95%CI 85-100%) and 96% sensitivity (95%CI 79-99%). Using this parameter, at PMCMR all the 8 patients with HCM were correctly identified with no false positive. Conclusions: PMCMR allows to identify HCM as cause of sudden death using the SD of WT >2.4 as diagnostic parameter.
ARTICLE | doi:10.20944/preprints202008.0252.v1
Subject: Physical Sciences, Mathematical Physics Keywords: post collapse entanglement; commutators pictures; force operator; labeling set
Online: 11 August 2020 (05:37:51 CEST)
n our previous paper, we showed that the so-called quantum entanglement also exists in classical mechanics. The inability to measure this classical entanglement was rationalized with the definition of a classical observer which collapses all entanglement into distinguishable states. It was shown that evidence for this primary coherence is Newton’s third law. However, in reformulating a "classical entanglement theory" we assumed the existence of Newton’s second law as an operator form where a force operator was introduced through a Hilbert space of force states. In this paper, we derive all related physical quantities and laws from basic quantum principles. We not only define a force operator but also derive the classical mechanic's laws and prove the necessity of entanglement to obtain Newton’s third law.
Subject: Environmental And Earth Sciences, Environmental Science Keywords: Post-2020; Global Biodiversity Framework; Zero draft; Aichi Targets; Convention on Biological Diversity; biodiversity; extinction; conservation; IUCN Red List
Online: 5 September 2020 (06:27:39 CEST)
In 2010, Parties to the Convention on Biological Diversity (CBD) adopted the Strategic Plan for Biodiversity 2011–2020 to address the loss and degradation of nature. Subsequently, most biodiversity indicators continued to decline. Nevertheless, conservation actions can make a positive difference for biodiversity. The emerging Post-2020 Global Biodiversity Framework has potential to catalyze efforts to ‘bend the curve’ of biodiversity loss. Thus, the inclusion of a goal on species, articulated as Goal B in the Zero Draft of the Post-2020 Framework, is essential. However, as currently formulated, this goal is inadequate for preventing extinctions, and reversing population declines; both of which are required to achieve the CBD’s 2030 mission. We contend it is unacceptable that Goal B could be met while most threatened species deteriorated in status and many avoidable species extinctions occurred. We examine the limitations of the current wording and propose an articulation with robust scientific basis. A goal for species that strives to end extinctions and recover populations of all species that have experienced population declines, and especially those at risk of extinction, would help to align actors towards the transformative actions and interventions needed for humans to live in harmony with nature.
ARTICLE | doi:10.20944/preprints201907.0210.v1
Subject: Medicine And Pharmacology, Pediatrics, Perinatology And Child Health Keywords: post-marketing surveillance; vaccine safety; pertussis; Tdap; pregnancy; infant
Online: 18 July 2019 (09:26:02 CEST)
We aimed to evaluate the safety of maternal Tdap we assessed health events by examining the difference in birth and hospital-related outcomes of infants with and without fetal exposure to Tdap. This was a retrospective cohort study using linked administrative datasets. The study population were all live-born infants in New Zealand (NZ) weighing at least 400 grams at delivery and born to women who were eligible for the government funded, national-level vaccination program in 2013. Infants were followed from birth up to one year of age. There were a total of 69,389 eligible infants in the cohort. Of these, 8,299 infants were born to 8,178 mothers exposed to Tdap (12%), primarily between 28-38 weeks gestation as per the national schedule. Among the outcomes, we found a reduced risk for moderate to late preterm birth, low birth weight, small for gestational age, large for gestational age, respiratory distress syndrome, transient tachypnea of newborn, tachycardia or bradycardia, haemolytic diseases, other neonatal jaundice, anaemia, syndrome of infant of mother with gestational diabetes, and hypoglycemia in infants born to vaccinated mothers. There was no association between maternal Tdap and stillbirth, infant Apgar score at 5 minutes after birth, microcephaly, asphyxia, sepsis or infection, or hypoxic ischemic encephalopathy. Infant exposure to Tdap during pregnancy was associated with a higher mean birthweight (not clinically significant) and higher odds for ankyloglossia and neonatal erythema toxicum diagnoses. There were insufficient observations to allow examination of the effect of Tdap on extreme preterm and very preterm birth, and infant death. Overall, we found no outcomes of concern associated with the administration of Tdap during pregnancy.
ARTICLE | doi:10.20944/preprints201808.0455.v1
Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: Anaemia; Stroke; Dementia; Risk; Vascular Dementia; Post-stroke dementia
Online: 27 August 2018 (11:11:59 CEST)
Background: Whilst lack of concentration is a known symptom of anaemia, its association with post-stroke dementia is unclear. Methods: We used data from a UK regional stroke register. To be eligible, patient must have survived to discharge and had anaemia by WHO criteria. Dementia status and other prevalent co-morbidities were assessed using ICD-10 codes. Patients were followed till May 2015 (mean follow-up 3.7 years, total person years = 27,769). Hazard Ratio for incident dementia was calculated using Cox-proportional hazards model controlling for potential confounders. Fine and Gray model was additionally constructed using mortality as the competing risk. Results: A total of 7,454 stroke patients were included with mean age (SD) of 75.9(12.3) years (50.2% men). Those with anaemia were older, has higher disability and co-morbidity burden prior to stroke. We observed a large amount of variation in the dementia incidence rates over time and that the hazard ratio increased every year. The significant association between anaemia and dementia incidence was lost after controlling for pre-stroke Modified Rankin score (HR1.17(0.97,1.40)). With every 20g/dL increase in Hb was associated with a significant reduction in the risk of dementia after adjustment for age, sex, stroke factors and disability but lost significance after adjustment for vascular risk factors. Competing risk analyses showed similar results. Conclusion: Whilst we found no evidence of anaemia as a risk factor for post-stroke dementia, the findings may be limited by potential under recognition of post stroke dementia.
REVIEW | doi:10.20944/preprints201807.0173.v1
Subject: Medicine And Pharmacology, Orthopedics And Sports Medicine Keywords: Static; Stretching; Post-Match; Soccer; Recovery; DOMS; Injury; Performance
Online: 10 July 2018 (11:53:41 CEST)
Soccer is the most played sport worldwide, with over 265 million participants. It is an incredibly demanding sport, with many different technical skills and physical loads placed on the body. This makes post-match recovery strategies amongst high level soccer players of great importance. The aim of this review is to summarize the existing literature on stretching for post-match recovery, examining its relation to injury prevention, Delayed Onset Muscle Soreness (DOMS), and performance. Scientific evidence of the highest quality and relevance was extracted and reviewed. Despite its common practice, evidence does not support static stretching as a modality to improve recovery post-match amongst soccer players. Larger trials with important outcome measures are needed to determine if a post-match stretching regimen to facilitate recovery exists.
ARTICLE | doi:10.20944/preprints201805.0231.v1
Subject: Social Sciences, Sociology Keywords: post-disaster community; sustainable development; social network; government management
Online: 16 May 2018 (11:04:53 CEST)
The current urban environment is faced with the potential threat of frequent natural disasters, and the sustainable development of post-disaster community has become a global issue. As an intrinsic motivation influencing the social interaction and capital operation of community, social network is an important mechanism promoting such sustainable development. However, the difference in social network caused by different member structure, spatial arrangement and management mechanism of post-disaster communities in different reconstruction modes has influenced such sustainable development process. Therefore, reasonable selection of reconstruction mode is crucial. This paper applied analytic hierarchy process to comprehensively measure and compare the social network strength in post-disaster communities in the four reconstruction modes adopted by the government of China, i.e. unified planning and unified construction, unified planning and independent construction, in situ reconstruction and relocation resettlement, with communities after the 2008 Sichuan earthquake in Chengdu, China as study objects from the perspective of three social relations (the relations between residents and residents, residents and managers, and residents and servers). The results showed that strong connections are generally presented in the social network of post-disaster communities in unified planning modes, that the strength is significantly higher than that of those in non-unified planning modes, and that the strength of UPIC communities is the highest. Meanwhile, government intervention, residents’ free participation and market operation are positively correlated to government trust, community interaction and community service respectively. The positive impact of government intervention is the most significant, but it has a peak value. No government management and excessive government intervention will exert negative impacts. The coordination of government, society and market is the key contents of post-disaster community reconstruction. The reconstruction modes based on “government leadership, resident participation and market operation” may become a feasible path for such sustainable development.
REVIEW | doi:10.20944/preprints201803.0168.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: connexins; gap junctions; transcription; translation; post-translational modifications; trafficking
Online: 20 March 2018 (05:27:38 CET)
Connexins are tetraspan transmembrane proteins that form gap junctions and facilitate direct intercellular communication, a critical feature for the development, function and homeostasis of tissues and organs. In addition, a growing number of gap junction-independent functions are being ascribed to these proteins. The connexin gene family is under extensive regulation at the transcriptional and post-transcriptional level, and undergoes numerous modifications at the protein level, including phosphorylation, which ultimately affects their trafficking, stability and function. Here, we summarize these key regulatory events, with emphasis on how these affect their multi-functionality in health and disease.
BRIEF REPORT | doi:10.20944/preprints202305.2234.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: SARS-CoV-2; booster vaccine; post-vaccine IgG antibody persistence
Online: 31 May 2023 (11:18:10 CEST)
Our aim was to evaluate the immune response of healthcare workers included in the RIPOVAC study, after receiving a booster dose (third dose), in terms of intensity and persistence of induced antibodies. In the second phase of RIPOVAC study, between December 2021 and January 2022, eight months after the second dose, 389 voluntary, immunocompetent, non-pregnant healthcare workers received a booster dose of SARS-CoV-2 vaccine, and a serum sample was obtained. Two groups of patients were established: with and without previous SARS-CoV-2 infection. In order to quantify anti-S1 IgG (AU/mL) we used CMIA (Abbott). All the health workers were anti-S IgG positive 8 months after receiving the booster dose of the vaccine, with a mean of 17040 AU/mL. In 53 patients without previous infection, antibody levels had increased by a mean of 10762 AU/mL. This figure is 7 times higher than the one produced after the second dose (1506 AU/mL). The booster dose produces a robust elevation of the antibody level, which persists at 8 months with levels up to values significantly higher than those reached after the second dose, that allow to predict a persistence of more than one year. The study demonstrates the efficacy of the booster dose of anti-SARS-CoV-2 vaccines.
REVIEW | doi:10.20944/preprints202207.0024.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: post-translation modifications; CK2; Huntington’s Disease; Kinase Inhibition; HTT phosphorylation
Online: 1 July 2022 (17:47:10 CEST)
Huntington’s Disease (HD) is a devastating neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the HTT gene, for which no disease modifying therapies are currently available. Much of the recent research has focused on developing therapies to directly lower HTT expression, and while promising, these therapies have presented several challenges regarding administration and efficacy. Another promising therapeutic approach is the modulation of HTT post-translational modifications (PTMs) that are dysregulated in disease and have shown to play a key role in HTT toxicity. Among all PTMs, modulation of HTT phosphorylation has been proposed as an attractive therapeutic option due to the possibility of orally administering specific kinase effectors. One of the kinases described to participate in HTT phosphorylation is Protein Kinase CK2. CK2 has recently emerged as a target for the treatment of several neurological and psychiatric disorders, although its role in HD remains controversial. While pharmacological studies in vitro inhibiting CK2 resulted in reduced HTT phosphorylation and increased toxicity, genetic approaches in mouse models of HD have provided beneficial effects. In this review we discuss potential therapeutic approaches related to the manipulation of HTT-PTMs with special emphasis on the role of CK2 as a therapeutic target in HD.
CONCEPT PAPER | doi:10.20944/preprints202111.0333.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Proteomics; Bottom-up; Top-down; Peptidoform; Proteoform; Post-translational modifications
Online: 18 November 2021 (14:41:02 CET)
Protein translational modifications (PTMs) generate an enormous, but as yet undetermined, expansion of the expressed proteoforms. In this Viewpoint, we firstly differentiate the concepts of proteoform and peptidoform by reviewing and discussing previous literature. We show that the current PTM biological investigation and annotation largely follow a PTM site-specific rather than proteoform-specific approach. We further illustrate a potentially useful matching strategy in which a particular “modified peptidoform” is matched to the corresponding “unmodified peptidoform” as a reference for the quantitative analysis between samples and conditions. We suggest this strategy could provide directly relevant information for learning the PTM site-specific biological functions. Accordingly, we advocate for the wider use of the nomenclature “peptidoform” in the future bottom-up proteomic studies.
CONCEPT PAPER | doi:10.20944/preprints202010.0368.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: proteoform; human genome project; proteomics; post-translational modification; human proteome
Online: 19 October 2020 (10:49:39 CEST)
Proteins are the primary effectors of function in biology, and thus complete knowledge of their structure and properties is fundamental to deciphering function in basic and translational research. The chemical diversity of proteins is expressed in their many proteoforms, which result from combinations of genetic polymorphisms, RNA splice variants and post-translational modifications. This knowledge is foundational for the biological complexes and networks that control biology, yet remains largely unknown. We propose here an ambitious initiative to define the human proteome; that is to generate a definitive reference set of the proteoforms produced from the genome. Several examples of the power and importance of proteoform-level knowledge in disease-based research are presented, along with a call for improved technologies in a two-pronged strategy to accomplish the Human Proteoform Project.