ARTICLE | doi:10.20944/preprints202203.0277.v1
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/preprints202112.0413.v1
Online: 24 December 2021 (23:40:18 CET)
Background Recently, a surge of COVID 19 was observed globally, regionally and nationally. With increasing numbers of cases, the frequency of long COVID is on the rise. Management and control of long COVID depend on changes in respect of human behaviors and requires an understanding of knowledge, attitudes, and practices (KAP) regarding health threats. MethodsA descriptive cross sectional study using online survey to gather data on the socio-economic background, knowledge, attitudes and practices on long-term complications of COVID. Results: Out of 201 respondents, 89.2% participants have heard about long-term complications of COVID 19. Only 35.9% have demonstrated adequate knowledge in the questions relating to co-morbidities and risk factors of COVID-19. A total of 92.2% believe that they should adhere to preventive measures following vaccination. Less than 60 % were following the advice on avoiding unnecessary travel and crowded places. Further, less than 50% were following COVID preventive measures. ConclusionAlthough the majority of participants have heard about long-term complications and common symptoms, the knowledge regarding co-morbidities that can lead to severe disease and long COVID was not satisfactory. The attitudes of the participants indicated increasing concern about long COVID. Practices indicate lack of adherence to key measures such as avoiding crowded places. These findings highlight the need for further increasing of awareness.
REVIEW | doi:10.20944/preprints202206.0004.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: Long-COVID; cognitive disorders; rehabilitation
Online: 1 June 2022 (05:50:58 CEST)
There is mounting evidence that patients with severe COVID-19 disease may have symptoms that continue beyond the acute phase, extending into the early chronic phase. Often referred to as 'Long COVID'. Simultaneously, case investigations have shown that COVID-19 individuals might have a variety of neurological problems. The accurate and accessible assessment of cognitive function in patients post COVID-19 infection is thus of increasingly high importance for both public and individual health. Little is known about the influence of COVID-19 on the general cognitive levels but more importantly, at sub functions level. Therefore, we first aim to summarize current level of evidence supporting a negative impact of COVID-19 infection on cognitive functions. 27 studies have been included in the systematic review representing a total of 94,103 participants (90,317 COVID-19 patients and 3,786 healthy controls). We then performed a meta-analysis summarizing the results of 5 studies (959 participants, 513 patients) to quantify the impact of COVID-19 on cognitive functions. The overall effect, expressed in Standardized Mean Differences, is -0.56 [95%CI -0.79 ; -0.34]. To prevent disability, we finally discuss the different approaches available in rehabilitation to help these patients and to avoid long-term complication.
ARTICLE | doi:10.20944/preprints202106.0011.v1
Subject: Life Sciences, Biochemistry Keywords: long covid; symptom cluster; persistent symptoms; long-term; Mexico; survey
Online: 1 June 2021 (09:44:47 CEST)
Recently, several reports have emerged describing the long-term consequences of COVID-19 that may affect multiple systems, suggesting its chronicity. As further research is needed, we conducted a longitudinal observational study to report the prevalence and associated risk factors of long-term health consequences of COVID-19 by symptom clusters in patients discharged from the Temporary COVID-19 Hospital (TCH) in Mexico City. Self-reported clinical symptom data were collected via telephone calls over 90 days post-discharge. Among 4670 patients discharged from the TCH, we identified 45 symptoms across eight symptom clusters (neurological; mood disorders; systemic; respiratory; musculoskeletal; ear, nose, and throat; dermatological; and gastrointestinal). We observed that the neurological, dermatological, and mood disorder symptom clusters persisted in >30% of patients at 90 days post-discharge. Although most symptoms decreased in frequency between day 30 and 90, alopecia and the dermatological symptom cluster significantly increased (p<0·00001). Women were more prone than men to develop long-term symptoms and invasive mechanical ventilation also increased the frequency of symptoms at 30-days post-discharge. Overall, we observed that symptoms often persisted regardless of disease severity. We hope these findings will help promote public health strategies that ensure equity in the access to solutions focused on the long-term consequences of COVID-19.
ARTICLE | doi:10.20944/preprints202103.0271.v1
Online: 9 March 2021 (12:37:24 CET)
Background The World Health Organization has recently recognized Long COVID, calling the international medical community to strengthen research and comprehensive care of patients with this condition. However, if Long COVID pertains to children as well is not yet clear. Methods An anonymous, online survey was developed by an organization of parents of children suffering from persisting symptoms since initial infection. Parents were asked to report signs and symptoms, physical activity and mental health issues. Only children with symptoms persisting for more than four weeks were included. Results 510 children were included (56.3% females) infected between January 2020 and January 2021. At their initial COVID-19 infection, 22 (4.3%) children were hospitalized. Overall, children had persisting COVID-19 for a mean of 8.2 months (SD 3.9). Most frequent symptoms were: Tiredness and weakness (444 patients, 87.1% of sample), Fatigue (410, 80.4%), Headache (401, 78.6%), Abdominal pain (387, 75.9%), Muscle and joint pain (309, 60.6%), Post-exertional malaise (274, 53.7%), rash (267, 52.4%). 484 (94.9%) children had had at least four symptoms. 129 (25.3%) children have suffered constant COVID-19 infection symptoms, 252 (49.4%) have had periods of apparent recovery and then symptoms returning, and 97 (19.0%) had a prolonged period of wellness followed by symptoms. Only 51 (10.0%) children have returned to previous levels of physical activity. Parents reported a significant prevalence of Neuropsychiatric symptoms. Conclusions Our study provides further evidence on Long COVID in children. Symptoms like fatigue, headache, muscle and joint pain, rashes and heart palpitations, and mental health issues like lack of concentration and short memory problems, were particularly frequent and confirm previous observations, suggesting that they may characterize this condition. A better comprehension of Long COVID is urgently needed..
REVIEW | doi:10.20944/preprints202209.0200.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: sequelae; COVID-19; SARS-COV-2; long-COVID; systematic review
Online: 14 September 2022 (08:50:08 CEST)
Background: COVID-19 made its debut as a pandemic in 2020; since then, more than 607 million cases and at least 6.5 million deaths have been reported worldwide. While the burden of disease has been described, the long-term effects or chronic sequelae are still being described. Objective: To describe the findings of a current systematic review of the long-term effects related to post-COVID-19 sequelae. Design: A systematic review was carried out in which cohort studies, case series, clinical case reports were included, and the PubMed, Scielo, SCOPUS and Web of Science databases were ex-tracted. Information published 2020 to June 1, 2022, was sought. Results: We reviewed 300 manuscripts during the first step of the literature review process. Then 260 abstracts were analyzed. In the end, we included 32 manuscripts: 9 for pulmonary, 6 for cardiac, 2 for renal, 9 for neurological and psychiatric, and 8 for cutaneous sequelae. Conclusion: Studies show that the most common sequelae are those linked to the lungs, followed by skin, cutaneous and psychiatric alterations. Women report a higher incidence of the sequelae, as well as those with comorbidities and severer COVID-19 history. The COVID-19 pandemic has not only caused death and disease since its apparition but has also sickened millions of people around the globe who potentially suffer from serious illnesses that will continue to add to the list of health problems and further burden healthcare systems around the world.
REVIEW | doi:10.20944/preprints202105.0055.v1
Subject: Life Sciences, Biochemistry Keywords: Coronaviruses; SARS-CoV-2; COVID-19; Viral Persistence; Reinfection; Long COVID
Online: 5 May 2021 (12:44:52 CEST)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) continues to wreak havoc threatening the public health services and imposing economic collapse worldwide. Tailoring public health responses to the SARS-CoV-2 pandemic depends on understanding the mechanism of viral replication, disease pathogenesis, and accurately identifying acute infections and mapping the spreading risk of hotspots across the globe. However, effective identification and isolation of persons with asymptomatic and mild SARS-CoV-2 infections remain the major obstacles to efforts in controlling the SARS-CoV-2 spread and hence the pandemic. Understanding the mechanism of persistent viral shedding, reinfection, and the post-acute sequalae of SARS-CoV-2 infection (PASC) is crucial in our efforts to combat the pandemic and provide better care and rehabilitation to survivors. Here we present a living literature review on SARS-CoV-2 viral persistence, reinfection and PASC. We also highlight potential areas of research to uncover putative links between viral persistence, intra-host evolution, host immune status, and protective immunity to guide and direct future basic science and clinical research priorities.
ARTICLE | doi:10.20944/preprints202111.0368.v1
Subject: Medicine & Pharmacology, Sport Sciences & Therapy Keywords: Long Covid; rehabilitation; virtual methods; multi-disciplinary team
Online: 19 November 2021 (15:00:47 CET)
Background: The COVID-19 pandemic has disproportionately affected people from more deprived communities. The experience of Long Covid is similarly distributed but very few investigations have concentrated on the needs of this population. The aim of this project was to co-produce an acceptable intervention for people with Long Covid, living in communities recognised as more deprived. Methods: The intervention was based on a multi-disciplinary team using approaches from sport and exercise medicine and functional rehabilitation. The co-production process was undertaken with a stakeholder advisory group and patient public involvement representation. This study identified participants by postcode and the indices of multiple deprivation (IMD); recruitment and engagement were supported by an existing health and wellbeing service. A virtual ‘clinic’ was offered with a team of professional practitioners who met participants three times each; to directly consider their needs and offer structured advice. The acceptability of the intervention was based on the individual’s participation and their completion of the intervention. Results: Ten participants were recruited with eight completing the intervention. The partnership with an existing community health and wellbeing service was deemed to be an important way of reaching participants. Two men and six women ages ranging from 38 to 73 were involved and their needs were commonly associated with fatigue, anxiety and depression with overall de-conditioning. None reported serious hardship associated with the pandemic although most were in self-employment/part-time employment or were not working due to retirement or ill-health. Two older participants lived alone, and others were single parents and had considerable challenges associated with managing a household alongside their Long Covid difficulties. Conclusions: This paper presents the needs and perspectives of eight individuals involved in the process and discusses the needs and preferences of the group in relation to their support for self- managed recovery from Long Covid.
COMMUNICATION | doi:10.20944/preprints202206.0325.v3
Subject: Medicine & Pharmacology, Cardiology 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/preprints202209.0084.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: long COVID; Post COVID-19 condition; sleep disorders, SARS-CoV-2; Coronavirus; children
Online: 6 September 2022 (10:01:25 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.
ARTICLE | doi:10.20944/preprints202208.0376.v1
Subject: Medicine & Pharmacology, Other Keywords: COVID-19; SARS-CoV-2; long-COVID; sequalae; symptoms; Latin America; high altitude
Online: 22 August 2022 (06:04:53 CEST)
Background: Some patients who have recovered from COVID-19 have experienced a range of persistent symptoms or the appearance of new ones after a SARS-CoV-2 infection. These symptoms can last from weeks to months, impacting everyday functioning to a significant number of patients. Methods: A cross-sectional analysis based on an online, self-reporting questionnaire was conducted in Ecuador from April to July 2022. Participants were invited by social media, radio, and TV to voluntarily participate in our study. A total of 2103 surveys were included in this study. We compared socio-demographic variables and long-term persisting symptoms at low (< 2,500 m) and high altitude (>2,500 m).Results: Overall, 1100 (52.3%) responders claimed to have long-term symptoms after SARS-CoV-2 infection. Most of these symptoms were reported by women (64.0%), the most affected group was young adults (68.5%), and the majority of long-haulers were mestizos (91.6%). We found that high altitude residents were more likely to report persisting symptoms (71.7%) versus those living at lower altitudes (29.3%). The most common symptoms were fatigue or tiredness (8.4%), hair loss (5.1%) and difficulty concentrating (5.0%). The highest proportion of persisting symptoms was observed among those who received an incomplete vaccine scheme.Conclusions: This is the first study describing post-COVID symptoms' persistence in low and high-altitude residents. Our findings demonstrate that women, especially those aging between 20-40, are more likely to describe sequalae associated with post-COVID. We also found that living at a high altitude was associated with earlier onset and longer symptom duration. Finally, we found a greater risk to report long lasting symptoms among women, those with previous comorbidities and those who had a severer acute SARS-CoV-2 infection.
REVIEW | doi:10.20944/preprints202103.0490.v1
Subject: Medicine & Pharmacology, Allergology 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.
Subject: Medicine & Pharmacology, Allergology Keywords: ME/CFS; education; medical school; teaching; long Covid; patient safety, NICE Guidelines, Health Act 1983, General Medical Council, GMC, Medical Schools Council, MSC, Long Covid.
Online: 16 March 2021 (12:16:27 CET)
Background and objectives: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome ME/CFS is a common complex multi-system disease with a significant impact on the quality of life of patients and their families, yet the majority of ME/CFS patients go unrecognised or undiagnosed. For two decades the medical education establishment in the UK has been challenged to remedy these failings, but little has changed. This study was designed to ascertain the current UK medical school education on ME/CFS and to identify challenges and opportunities to inform the future of medical education. Materials and methods: A questionnaire, developed under the guidance of the Medical Schools Council, was sent to all 34 UK Medical Schools to collect data for the academic year 2018-2019. Results: Responses were provided by 22 out of a total of 34 medical schools (65%). 59% of respondents taught ME/CFS, led by specialists drawn from 6 medical disciplines. Teaching delivery was usually by lecture; however, discussion case studies and e-learning were used. 7 schools included questions on ME/CFS in their examinations and 3 schools reported likely clinical exposure to ME/CFS patients. 64% of respondents were interested in receiving further teaching aids in ME/CFS. None of the schools shared details of their teaching syllabus so it was not possible to ascertain what students were being taught. Conclusions: UK medical school teaching in ME/CFS is shown to be inadequate. Several medical disciplines, with known differences about the disease, need to set these aside to give greater clarity in teaching undergraduates so they can more easily recognise and diagnose ME/CFS. Improvements are proposed in ME/CFS medical education consistent with the international paradigm shift in biomedical understanding of this disease. Many medical schools (64% of respondents) acknowledge this need by expressing a strong appetite for the development of further teaching aids and materials. The GMC and MSC are called upon to use their considerable influence to bring about the appropriate changes to medical school curricula so future doctors can recognise, diagnose and treat ME/CFS. The GMC should also consider creating a registered speciality encompassing ME/CFS, post viral fatigue and Long Covid.
REVIEW | doi:10.20944/preprints202208.0239.v1
Subject: Medicine & Pharmacology, Nursing & Health Studies Keywords: long-term care; healthcare workers; mental health; moral distress; resilience; COVID-19
Online: 12 August 2022 (12:43:46 CEST)
Healthcare workers (HCWs) in long-term care (LTC) faced and continue to experience significant emotional and psychological distress throughout the pandemic. Despite this, little is known about the unique experiences of LTC workers. This scoping review synthesizes existing research on the experiences of HCWs in LTC during the COVID-19 pandemic. Following Arksey and O’Malley’s framework, data were extracted from six databases from inception of the pandemic to June 2022. Among 3,808 articles screened, 40 articles were included in the final analysis. Analyses revealed three interrelated themes: carrying the load (moral distress); building pressure and burning out (emotional exhaustion); and working through it (a sense of duty to care). Given the impacts of the pandemic on both HCW wellbeing and patient care, every effort must be made to address the LTC workforce crisis and evaluate best practices for supporting HCWs experiencing mental health concerns during and post-COVID-19.
REVIEW | doi:10.20944/preprints202012.0242.v1
Subject: Medicine & Pharmacology, Allergology Keywords: COVID-19; SARS-CoV-2; long-haul; inflammation; tissue damage; drug repurposing
Online: 10 December 2020 (09:42:20 CET)
Long-haul COVID-19 illness first gained widespread recognition among social support groups and later in scientific and medical communities. This illness is mysterious as it affects COVID-19 survivors at all levels of disease severity, even younger adults and children. While the precise definition may be lacking, the defining symptoms are fatigue, dyspnea, and headache that last for months after hospital discharge. The less typical symptoms may include cognitive impairments, chest and joint pains, myalgia, smell and taste dysfunctions, cough, mood changes, and gastrointestinal and cardiac issues. Presently, there is limited literature discussing the possible pathophysiology, risk factors, and treatments in long-haul COVID-19, which the current review aims to address. In brief, long-haul COVID-19 may be driven by long-term lung and brain damage and unresolved inflammation from multiple sources. The associated risk factors may include female sex, more than five early symptoms, early dyspnea, and specific biomarkers like D-dimer. While only rehabilitation training has been useful for long-haul COVID-19, therapeutics repurposed from mast cell activation syndrome, myalgic encephalomyelitis/chronic fatigue syndrome, and pulmonary fibrosis also hold potential. In sum, this review hopes to provide the current understanding of what is known about long-haul COVID-19.
BRIEF REPORT | doi:10.20944/preprints202203.0370.v1
Subject: Medicine & Pharmacology, Nursing & Health Studies Keywords: COVID-19; visitation restrictions; psychological distress; cognitive disfunction; long-term care; rehabilitation ward
Online: 28 March 2022 (15:13:31 CEST)
This report is a narrative of a certified nurse working on a long-term rehabilitation ward for patients with dementia in Japan during the early phase of the COVID-19 pandemic. During this time visitation restrictions had been implemented to prevent the spread of COVID-19 causing psychological distress for patients and their families which nurses had to cope with . The nurse was interviewed twice September–October 2020. The recordings were transcribed verbatim and analysed thematically. Three themes were identified relating to changes in care in response to the pandemic which nurses had to adapt to: the risk of collapse of family members’ roles, anxiety caused by patients forgetting family members and family memories and increased disorientation. During the pandemic, nursing care needs to adapt, ensuring that family attachments and ties continue and minimizing the disruption caused by the pandemic, while ensuring that everyone remains Covid-safe.
ARTICLE | doi:10.20944/preprints202207.0380.v1
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: SARS-CoV-2; COVID-19; autoantibodies; autoimmune endocrinopathies; long-COVID syndrome; molecular mimicry; thyroid gland; adrenals; pituitary; Langerhans’ islets
Online: 26 July 2022 (03:42:01 CEST)
Molecular mimicry between human and microbial/viral/parasite peptides is common and for a long time is associated with the etiology of autoimmune disorders provoked by exogenous pathogens. Increasing evidence accumulated from the past years suggests a strong correlation between the SARS-CoV-2 infection and autoimmunity. The article analyzes the immunogenic potential of the peptides shared between SARS-CoV-2 spike glycoprotein (S-protein and antigens of human endocrinocytes involved in most common autoimmune endocrinopathies. Totally the study revealed 14 pentapeptides shared by S-protein of SARS-CoV-2 and autoantigens of thyroid, pituitary, adrenal cortex and Langerhans’ islets beta-cells, 12 of them belong to immunoreactive epitopes of SARS-CoV-2. The discussion of the data links the results with clinical correlates of COVID-associated autoimmune endocrinopathies. Most common of them is an autoimmune thyroid disease, so the majority of shared pentapeptides belong to marker autoantigens of this disease. Most important in pathogenesis of severe COVID-19, according authors’ opinion, can be autoimmunity against adrenals, because their adequate response prevents from excessive systemic action of inflammatory mediators which cause cytokine storm and hemodynamic shock. The criticism of antigen mimicry concept is given with a statement that peptide sharing is not a guarantee, but just a prerequisite of autoimmunity excess provocation. The last event occurs in carriers of certain HLA haplotypes and in case when shared peptide is used in antigen processing only [1 figure, 5 tables, bibliography 38 references].
ARTICLE | doi:10.20944/preprints202206.0010.v1
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: COVID-19; ARDS; Cytokine Storm; Spike S1 protein; SARS-CoV-2, Long COVID; ACE2; A549 cells; Caco-2 cells
Online: 1 June 2022 (09:49:27 CEST)
The Coronavirus disease 2019 (COVID-19) pandemic began in Jan. 2020 in Wuhan, China with a new coronavirus designated SARS-CoV-2. The principle cause of death from COVID-19 disease quickly emerged as Acute Respiratory Distress Syndrome (ARDS). A key ARDS pathogenic mechanism is the “Cytokine Storm”. This is a dramatic increase in the blood of inflammatory cytokines. In the last 2 years of the pandemic new pathology has emerged in COVID-19 survivors in which a variety of long-term symptoms emerge. This condition is called “Long COVID”. The spike protein on the surface of the virus (target for the new mRNA/DNA vaccines) is composed of joined S1-S2 subunits. Upon S1 bind-ing to the human ACE2 receptor on cells, the S1 subunit is cleaved and the S2 subunit me-diates entry of the virus. The S1 protein is then released into the blood, which might be one of the pivotal triggers for initiation and/or perpetuation of the cytokine storm. In this study, we tested the hypothesis that the spike S1 protein may activate inflammatory sig-naling and cytokine production independent of the virus. Our data support a potential role for spike S1 activation of inflammatory signaling and cytokine production in human lung and intestinal epithelial cells in culture. These data support a potential role for the SARS-CoV-2 spike S1 protein in COVID-19 pathogenesis.
HYPOTHESIS | doi:10.20944/preprints202208.0398.v1
Subject: Life Sciences, Immunology 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/preprints202111.0478.v1
Subject: Medicine & Pharmacology, General Medical Research 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/preprints201811.0634.v1
Subject: Physical Sciences, Particle & Field Physics Keywords: Neutrino oscillations; neutrino mixing; long baseline
Online: 30 November 2018 (11:07:53 CET)
We study the possibility of determining the octant of the neutrino mixing angle 23, that is, whether 23 > 45 or 23 < 45, in long baseline neutrino experiments. Here we numerically derived the sensitivity limits within which these experiments can determine, by measuring the probability of the ! e transitions, the octant of 23 with a 5 certainty. The interference of the CP violation angle with these limits, as well as the effects of the baseline length and the run-time ratio of neutrino and antineutrino modes of the beam have been analyzed.
ARTICLE | doi:10.20944/preprints202207.0426.v1
Subject: Mathematics & Computer Science, Applied Mathematics Keywords: SARS-CoV-2 infection; innate immune response; antigen-specific immune response; kinetic coordination; mathematical model; pathogenesis, long COVID-19
Online: 27 July 2022 (15:11:44 CEST)
A calibrated mathematical model of antiviral immune response to SARS-CoV-2 infection is developed. The model considers the innate and antigen-specific responses to SARS-CoV-2 infection. Recently published data sets from human challenge studies with SARS-CoV-2 were used for parameter estimation. Understanding the regulation of multiple intertwined reaction components of the immune system is necessary for linking the clinical phenotypes of COVID-19 with the kinetics of immune responses. Consideration of multiple immune reaction components in a single calibrated mathematical model allowed us to address some fundamental issues related to pathogenesis of COVID-19, i.e. sensitivity of the peak viral load to parameters characterizing the specific response components, the kinetic coordination of the individual responses, and the factors favoring a prolonged viral persistence. The model provides a tool for predicting the infectivity of patients, i.e. the amount of virus which is transmitted via droplets from the person infected with SARS-CoV-2, depending on the time of infection. The thresholds in the relative unbalance between innate and adaptive response parameters which lead to a prolonged persistence of SARS-CoV-2 due to the loss of a kinetic response synchrony/coordination were identified.
ARTICLE | doi:10.20944/preprints202210.0054.v1
Subject: Geography, Social Sciences Keywords: Cameroon; rainfall; long-term variability; trend tests
Online: 6 October 2022 (08:17:50 CEST)
The rainfall study in the long term is essential for climatic change understanding and socioeconomic development. The main goal of this study is to explore the spatial and temporal variations of precipitation in different time scales (seasonal and annual) in Cameroon. The Mann–Kendall and Pettitt tests were applied to analyze the precipitation variability. On temporal plan, the different regions of Cameroon have recorded significant drops in annual rainfall that Pet-titt's test generally situates around the 1970s. The decreases observed for the northern part of Cameroon regions are between –5.4% (Adamawa) and –7.4% (Far North). Those of west-ern part regions oscillate between –7.5% (South-West) and –12.5% (West). The southern part of Cameroon regions recorded decreases varying between –4.3% (East) and –5.9% (Center). On spatial plan, the divisions of the northern, western and southern parts of Cameroon respectively recorded after the 1970s (a pivotal period in the evolution of precipitation on temporal plan), a precipitation decrease towards the South, the South-West and the West. This study's findings could be helpful for planning and managing water resources in Cameroon.
ARTICLE | doi:10.20944/preprints202201.0270.v1
Subject: Mathematics & Computer Science, Other Keywords: Road accidents; Brazil; fractional integration; long memory
Online: 19 January 2022 (11:45:26 CET)
This paper deals with the analysis of trends in road accidents on major highways in Brazil. Using updated time series techniques, our results indicate that a low degree of long memory was detected in the series with shocks having transitory effects over time. We further find that the number of accidents taking place in Brazil has been reducing over time, though in the presence of negative shocks, the recovery is not going to be immediate due to the long memory nature of the data. Despite the absence of relevant investment relating to infrastructure expansion, it is worth mentioning the consolidation of a nationwide tolled road system in Brazil involving concessions to private administrators, alongside more severe traffic laws that can impose limitations on driving licences.
ARTICLE | doi:10.20944/preprints201906.0117.v1
Online: 13 June 2019 (09:26:20 CEST)
The whole genome sequencing (WGS) has become a crucial tool to understand genome structure and genetic variation. The MinION sequencing of Oxford Nanopore Technologies (ONT) is an excellent approach for performing WGS and has advantages in comparison with other Next-Generation Sequencing (NGS): It is relatively inexpensive, portable, has simple library preparation, can be monitored in real-time, and has no theoretical limits on read length. Sorghum bicolor (L.) Moench is diploid (2n = 2x = 20) with a genome size of about 730 Mb, and its genome sequence information is released in the Phytozome database. Therefore, sorghum can be be used as a good reference. However, plant species have complex and large genomes compared to animals or microorganisms. As a result, complete genome sequencing is difficult for plant species. MinION sequencing that produces long-reads can be an excellent tool to overcome the weak assembly of short-reads generated from NGS by minimizing the generation of gaps or covering the repetitive sequence that appears on the plant genome. Here, we conducted the genome sequencing for S. bicolor cv. BTx623 using the MinION platform and obtained 895,678 reads and 17.9 gigabytes(Gb) (ca. 25X coverage of reference) from long-read sequence data. Through a de novo assembly using two different tools and mapped assembled contigs against the sorghum reference genome, a total of 6,124 contigs (covering 45.9%) were generated from Canu, and a total of 2,661 contigs (covering 50%) were generated from Minimap and Miniasm with a Racon pipeline. Our results provide a pipeline of long-read sequencing analysis for plant species using the MinION platform and a clue to determine the total sequencing scale for optimal coverage based on various genome sizes.
ARTICLE | doi:10.20944/preprints201902.0241.v1
Online: 26 February 2019 (12:45:04 CET)
Here, we have discovered a X-ray excited long afterglow phosphor β-NaYF4: Tb3+. After the irradiation of X-ray, the green emission can persist for more than 240 h. After 36 h, the afterglow intensity arrived at 0.69 mcd•m-2, which can clearly be observed by naked eyes. Even after 84 h, the afterglow emission brightness still reached 0.087 mcd•m-2. Also, combined with the results of thermoluminescence and photoluminescence, the super long afterglow emission of β-NaYF4: Tb3+ can be ascribed to the tunneling model associated with F centers. More importantly, the super long green afterglow emission of β-NaYF4: Tb3+ has been successfully used as in vivo light source to activate g-C3N4 for photodynamic therapy（PDT）and bacteria destruction. Furthermore, super long persistent luminescence of β-NaYF4: Tb3+ could be repeatedly charged by X-ray for many circulations, which indicates that the phosphors have high photo stability under repeated cycles of alternating X-ray irradiation.
CASE REPORT | doi:10.20944/preprints201809.0410.v1
Subject: Behavioral Sciences, Social Psychology Keywords: long-term care, technology, therapy, virtual reality
Online: 20 September 2018 (13:34:02 CEST)
In this study, 6 residents of a long-term care facility were asked to try on Virtual Reality glasses and report their first experiences with Virtual Reality. The results show that Virtual Reality is of great interest to elderly residents of in-patient long-term care facilities. The wearing period was longer than expected and no symptoms of cyber sickness occurred. For the residents it was exciting to explore the virtual environments. Austrian destinations, nature scenes in the mountains and forests but also trips to the zoo, the museum, in churches or even densely populated areas like shopping streets or train stations would be places for the residents, they would like to explore virtually. Far-off destinations such as Rio de Janeiro or the Caribbean are more of an exception. Biographically relevant places such as the parental home or the location of their wedding were not named. Concerning the usability, an adjustment of the VR glasses is necessary for a longer-term use in any case.
Subject: Life Sciences, Biochemistry Keywords: CA3-CA1 synapses; NMDA; AMPA; systems biology; multiscale modeling; synaptic plasticity; long term potentiation; long term depression; hippocampus
Online: 8 January 2021 (13:17:31 CET)
Inside hippocampal circuits, neuroplasticity events that individual cells may undergo during synaptic transmissions occur in the form of Long Term Potentiation (LTP) and Long Term Depression (LTD). The high density of NMDA receptors expressed on the surface of the dendritic CA1 spines confers to hippocampal CA3-CA1 synapses, the ability to easily undergo NMDA-mediated LTP and LTD, that is essential for some forms of explicit learning in mammals. Providing a comprehensive kinetic model that can be used for running computer simulations of the synaptic transmission process is currently a major challenge. Here, we propose a compartmentalized kinetic model for CA3-CA1 synaptic transmission. Our major goal was to tune our model in order to predict the functional impact caused by disease associated variants of NMDA receptors related to severe cognitive impairment. Indeed, for variants Glu413Gly and Cys461Phe, our model predicts negative shifts in the glutamate affinity and changes in the kinetic behavior, consistent with experimental data. These results pinpoint to the predictive power of this multiscale viewpoint, which aims to integrate the quantitative kinetic description of large interaction networks typical of system biology approaches with a focus on the quality of few, key, molecular interactions typical of structural biology ones.
HYPOTHESIS | doi:10.20944/preprints202104.0060.v1
Subject: Behavioral Sciences, Applied Psychology Keywords: Human Memory; Long-term Memory; Episodic; Implicit; Explicit
Online: 2 April 2021 (12:02:21 CEST)
Memory is probably one of the most complex cognitive functions of the human, and in many years, thousands of studies have helped us to better recognize this brain function. One of the reference textbooks in neuroscience, which has also elaborated on the memory function, is written by Prof. Kandel and his colleagues. In this book, I encountered a number of ambiguities when it was explaining the memory system. Here, I am sharing those points, either to find an answer for them, or to let them be a suggestion for our future works. Prof. Kandel has spent most of his meritorious lifetime on studying the memory system; however, the brain is extremely complex, and as a result, we still have many years to comprehensively understand the neural mechanisms of brain functions.
ARTICLE | doi:10.20944/preprints202102.0185.v1
Subject: Earth Sciences, Atmospheric Science Keywords: atmosphere; aerosol; background; particle size; long term; Mediterranean
Online: 8 February 2021 (10:56:35 CET)
The Eastern Mediterranean is a highly populated area with air quality problems as well where climate change already is noticed by higher temperatures and changing precipitation pattern. The anthropogenic aerosol affects health and changing concentra-tions and properties of the atmospheric aerosol affect radiation balance and clouds. Continuous long-term observations are essential in assessing the influence of anthro-pogenic aerosols on climate and health. We present 6 years of observations from Navarino Environmental Observatory (NEO), a new station located at the south west tip of Pelo-ponnese, Greece. The two sites at NEO, were evaluated to show the influence of the local meteorology but also to assess the general background aerosol possible. It was found that the background aerosol was originated from aged European aerosols and was strongly influenced by biomass burning, fossil fuel combustion, and industry. When subsiding into the boundary layer, local sources contributed in the air masses moving south. Mesoscale meteorology determined the diurnal variation of aerosol properties such as mass and number by means of typical sea breeze circulation, giving rise to pronounced morning and evening peaks in pollutant levels. While synoptic scale meteorology, mainly large-scale air mass transport and precipitation, strongly influenced the season-ality of the aerosol properties.
ARTICLE | doi:10.20944/preprints202008.0095.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: long noncoding RNA; PVT1; MYC; bromodomain; multiple myeloma
Online: 4 August 2020 (11:31:37 CEST)
Abstract: Long noncoding RNAs (lncRNAs) are deregulated in human cancers and are associated with disease progression. Plasmacytoma Variant Translocation 1 (PVT1), an lncRNA, is located adjacent to MYC, linked to multiple myeloma (MM). PVT1 is expressed in MM and is associated with carcinogenesis, however, its role and regulation machinery remain uncertain. We examined PVT1/MYC expression through real time PCR in plasma cells purified from 59 MGUS and 140 MM patients. MM cell lines KMS11, KMS12PE, OPM2, and RPMI8226 were treated with JQ1, a MYC superenhancer inhibitor, or MYC inhibitor 10058-F4. The expression levels of PVT1 and MYC were significantly higher in MM than in MGUS (p < 0.0001), and showed positive correlation with disease progression (r = 0.394, p < 0.0001). JQ1 inhibited cell proliferation and decreased the expression levels of MYC and PVT1. However, 10054-F4 did not alter the expression level of PVT1. The positive correlation between MYC and PVT1 in patients, synchronous downregulation of MYC and PVT1 by JQ1, and no effect of MYC inhibitor on PVT1 expression suggest that the expression of these two genes is coregulated by a superenhancer. Cooperative effects between these two genes may contribute to MM pathogenesis and progression.
ARTICLE | doi:10.20944/preprints202007.0640.v1
Subject: Engineering, Energy & Fuel Technology Keywords: long-term energy storage; fossil fuels; energy transition
Online: 26 July 2020 (16:38:35 CEST)
Great Britain’s stocks of coal, natural gas, and petroleum have seen major changes to the levels of stored energy over the years 2005 to 2019, a reduction of 200 TWh (35%) from 570 TWh to 370 TWh. The transformation of its electrical system over this timeframe saw a reduction in coal generation, leading to a corresponding reduction of the levels of stockpiled coal of 85 TWh (68%), partially offset by an increase in the stocks of biomass for electrical generation. The reduction in natural gas storage of 24 TWh (44%) was primarily due to the closure of Britain’s only long-term seasonal natural gas storage facility in January 2018. This was partially offset by the construction of medium-term natural gas storage facilities and the use of LNG storage in the years preceding its closure. For stocks of crude oil and oil products the reduction was 35 TWh (21%), linked to the overall reduction in demand.
ARTICLE | doi:10.20944/preprints201910.0180.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: long term survival; Glioblastoma; IDH; EGFR; Ki67; p53
Online: 16 October 2019 (08:30:25 CEST)
Background: Glioblastomas (GBM) is generally burdened, to date, by a dismal prognosis, although Long Term Survivors have a relatively significant incidence. Our specific aim was to determine the exact impact of many surgery-, patient- and tumor-related variable on Survival parameters. Methods: The surgical, radiological and clinical outcomes of patients have been retrospectively reviewed for the present study. All the patients have been operated on in our Institution and classified according their Overall Survival in LTS (Long Term Survivors) and STS (Short Term Survivors). A thorough Review of our surgical series was conducted to compare the oncologic results of the patients in regards to 1. Surgical , 2. Molecular, and 3.Treatment related features. Results: A total of 177 patients were included in the final cohort. Extensive statistical analysis by means of univariate, multivariate and survival analyses disclosed a survival advantage for patients presenting a younger age, a smaller lesion and a better functional status at presentation. From the Histochemical point of view, Ki67(%) was the strongest predictor of better oncologic outcomes. A stepwise analysis of variance outlines the existence of 8 prognostic subgroups according to the molecular patterns of Ki67 overexpression and EGFR, p53 and IDH mutations. Conclusions: On the ground of our statistical analyses we can affirm that the following factors were significant predictors of survival advantage: KPS, Age, Volume of the lesion, Motor disorder at presentation, a Ki67 overexpression. A fine molecular profiling is feasible to precisely stratify the prognosis of GBM patients.
ARTICLE | doi:10.20944/preprints201903.0157.v1
Subject: Life Sciences, Molecular Biology Keywords: long non-coding RNA; hESC; cardiomyocyte; RNA-seq
Online: 15 March 2019 (02:11:52 CET)
Long non-coding RNAs (lncRNAs) have been found to be involved in many biological processes, including the regulation of cell differentiation, but a complete characterization of lncRNA is still lacking. Additionally, there is evidence that lncRNAs interact with ribosomes, raising questions about their functions in cells. Here, we used a developmentally staged protocol to induce cardiogenic commitment of hESCs and then investigated the differential association of lncRNAs with polysomes. Our results identified lncRNAs in both the ribosome-free and polysome-bound fractions during cardiogenesis and showed a very well-defined temporal lncRNA association with polysomes. Clustering of lncRNAs was performed according to the gene expression patterns during the five timepoints analyzed. In addition, differential lncRNA recruitment to polysomes was observed when comparing the differentially expressed lncRNAs in the ribosome-free and polysome-bound fractions or when calculating the polysome-bound vs ribosome-free ratio. The association of lncRNAs with polysomes could represent an additional cytoplasmic role of lncRNAs, e.g., in translational regulation of mRNA expression.
REVIEW | doi:10.20944/preprints201705.0194.v1
Subject: Mathematics & Computer Science, General Mathematics Keywords: long-range dependence; Hurst effect; fractionallydifferenced models; Mandelbrot
Online: 26 May 2017 (18:36:50 CEST)
Long memory plays an important role in many fields by determining the behaviour and predictability of systems; for instance, climate, hydrology, finance, networks and DNA sequencing. In particular, it is important to test if a process is exhibiting long memory since that impacts the accuracy and confidence with which one may predict future events on the basis of a small amount of historical data. A major force in the development and study of long memory was the late Benoit B. Mandelbrot. Here we discuss the original motivation of the development of long memory and Mandelbrot's influence on this fascinating field. We will also elucidate the sometimes contrasting approaches to long memory in different scientific communities
ARTICLE | doi:10.20944/preprints201611.0056.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: long-acting injectable; antipsychotic; decision-making; guidelines; schizophrenia
Online: 10 November 2016 (07:00:52 CET)
The purposes of this study were to identify clinician’s characteristics associated with higher prescription rates of long-acting injectable (LAI) antipsychotics, as well as the information sources influencing medical decision-making about treatment of schizophrenia. We surveyed 202 psychiatrists during 6 regional French conferences (Bordeaux, Lyon, Marseille, Nice, Paris, Strasbourg). Data on the characteristics of practice, prescription rates of antipsychotic and information sources about their clinical decisions were collected. Most of psychiatrists used second-generation antipsychotic (SGA), and preferentially an oral formulation, in the treatment of schizophrenia. SGA LAI was prescribed to 30.4% of schizophrenic patients. The duration and the type of practice did not influence the class or formulation of antipsychotics used. The clinicians following the higher percentage of schizophrenic patients were associated with the higher use of LAI antipsychotics and the lower use of oral SGA. Personal experience, government regulatory approval and guidelines for the treatment of schizophrenia were the 3 main contributing factors guiding the clinical decision-making of clinicians about treatment of schizophrenia. The more clinicians follow schizophrenic patients, the more they use LAI antipsychotic. The development of specialised programmes with top specialists should lead to better use of LAI in the treatment of schizophrenia.
ARTICLE | doi:10.20944/preprints202206.0207.v1
Subject: Biology, Animal Sciences & Zoology Keywords: Germinal Center; Herpesvirus; Recombinant protein; rgD5; Vaccine; Long-Lasting
Online: 14 June 2022 (16:21:47 CEST)
Bovine herpesvirus (BoHV)-5 is a worldwide distributed pathogen usually associated with a lethal neurological disease (meningoencephalitis) in dairy and beef cattle resulting in important economic losses due to the cattle industry. Using recombinant glycoprotein D of BoHV-5 (rgD5), we evaluated the long-duration humoral immunity of the recombinant vaccines in a cattle model. Here we report that two doses of intramuscular immunization, particularly with the rgD5ISA vaccine, are superior to iBoHV-5ISA immunization in the induction of long-lasting antibody responses. Recombinant gD5 antigen elicited tightly mRNA transcription of the Bcl6 and the chemokine receptor CXCR5 which mediate memory B cells and long-lived plasma cells in germinal centers (GCs). In addition, using an in-house Enzyme-Linked Immunosorbent Assay (ELISA) we observed higher and earlier responses of rgD5-specific IgG antibody and the upregulation of mRNA transcription of IL2, IL4, IL10, IL15 and IFN-γ cytokines in rgD5 vaccinated cattle, indicating a mixed immune response. We further show that rgD5 immunization provides protection against both BoHV -1 and -5. Our findings indicate that the rgD5-based vaccine represents an effective vaccine strategy to induce an efficient control of alpha-herpesviruses.
ARTICLE | doi:10.20944/preprints202107.0122.v1
Subject: Medicine & Pharmacology, Allergology Keywords: peri-implantitis; electrolytic cleaning; air abrasive; augmentation; long term
Online: 6 July 2021 (08:06:56 CEST)
Background: this RCT assesses the 18 months clinical outcomes after regenerative therapy of periimplantitis lesions using either an electrolytic method (EC) to remove biofilms or a combination of powder spray and electrolytic method (PEC). Materials and Methods: Twenty-four patients (24 implants) suffering from periimplantitis were randomly treated by EC or PEC followed by augmentation and submerged healing. Probing pocket depth (PPD), Bleeding on Probing (BoP), suppuration and standardized radiographs were assessed before surgery (T0), 6 months after augmentation (T1), 6 (T2) and 12 (T3) months after replacement of the restoration. Results: Mean of PPD changed from 5.8 ± 1.6 mm (T0) to 3.1 ± 1.4 mm (T3). While BoP and suppuration at T0 was 100 % BoP decreased at T2 to 36.8 % and at T3 to 35.3 %. Suppuration could be found 10.6% at T2 and 11.8% at T3. Radiologic bone level measured from the implant shoulder to the first visible bone to implant contact was 4.9 ± 1.9 mm at me-sial and 4.4 ± 2.2 mm at distal sites (T0) and 1.7 ± 1.7 mm and 1.5 ± 17 mm at T3. Conclusions: Significant radiographic bone fill and improvement of clinical parameters were demonstrated 18 months after therapy.
ARTICLE | doi:10.20944/preprints202101.0134.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Cardiac arrest; normothermia; EEG; SSEP; GWR; long term predictors
Online: 8 January 2021 (10:26:27 CET)
Introduction Early prediction of long term outcomes in patients resuscitated after cardiac arrest (CA) is still challenging. Guidelines suggested a multimodal approach combining multiple predictors. We evaluated whether the combination of the electroencephalography (EEG) reactivity, somatosensory evoked potentials (SSEPs) cortical complex and Gray to White matter ratio (GWR) on brain computed tomography (CT) at different temperatures could predict survival and good outcome at hospital discharge and after six months. Methods We performed a retrospective cohort study including consecutive adult, non-traumatic patients resuscitated from out-of-hospital CA who remained comatose on admission to our intensive care unit from 2013 to 2017. We acquired SSEPs and EEGs during the treatment at 36°C and after rewarming at 37°C, Gray to white matter ratio (GWR) was calculated on the brain computed tomography scan performed within six hours of the hospital admission. We primarily hypothesized that SSEP was associated with favorable functional outcome at distance and secondarily that SSEP provides independent information from EEG and CT. Outcomes were evaluated using the Cerebral Performance Category (CPC) scale at six months from discharge. Results Of 171 resuscitated patients, 75 were excluded due to missing of data or uninterpretable neurophysiological findings. EEG reactivity at 37 °C has been shown the best single predictor of good outcome (AUC 0.803) while N20P25 was the best single predictor for survival at each time point. (AUC 0.775 at discharge and AUC 0.747 at six months follow up) Predictive value of a model including EEG reactivity, average GWR, and SSEP N20P25 amplitude was superior (AUC 0.841 for survival and 0.920 for good outcome) to any combination of two tests or any single test. Conclusion Our study, in which life-sustaining treatments were never suspended, suggests SSEP cortical complex N20P25, after normothermia ad off sedation, is a reliable predictor for survival at any time. When SSEP cortical complex N20P25 is added into a model with GWR average and EEG reactivity, the predictivity for good outcome and survival at distance is superior than each single test alone.
REVIEW | doi:10.20944/preprints202012.0779.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Social isolation; risk factors; older adults; long-term care
Online: 31 December 2020 (09:24:17 CET)
Objectives: A wealth of literature has established risk factors for social isolation among older people, however much of this research has focused on community-dwelling populations. Relatively little is known about how risk of social isolation is experienced among those living in long-term care (LTC) homes. We conducted a scoping review to identify possible risk factors for social isolation among older adults living in LTC homes. Methods: A systematic search of five online databases retrieved 1535 unique articles. Eight studies met the inclusion criteria. Results: Thematic analyses revealed that possible risk factors exist at three levels: individual (e.g., communication barriers), systems (e.g., location of LTC facility), and structural factors (e.g., discrimination). Discussion: Our review identified several risk factors for social isolation that have been previously documented in literature, in addition to several risks that may be unique to those living in LTC homes. Results highlight several scholarly and practical implications.
REVIEW | doi:10.20944/preprints202012.0184.v1
Subject: Life Sciences, Biochemistry Keywords: C2H2 proteins; CTCF; LDB1; chromatin insulator; long-distance interactions
Online: 8 December 2020 (08:29:36 CET)
In higher eukaryotes, enhancers determine the activation of developmental gene transcription in specific cell types and stages of embryogenesis. Enhancers transform the signals produced by various transcription factors within a given cell, activating the transcription of the targeted genes. Often, developmental genes can be associated with dozens of enhancers, some of which are located at large distances from the promoters that they regulate. Currently, the mechanisms that underly the specific distance interactions between enhancers and promoters remain unknown. This review describes the properties and activities of enhancers and discusses the mechanisms of distance interactions and potential proteins involved in this process.
ARTICLE | doi:10.20944/preprints202007.0509.v1
Subject: Medicine & Pharmacology, Ophthalmology Keywords: laser excimer; myopia surgery; long term; Femto-LASIK; PRK
Online: 22 July 2020 (09:53:46 CEST)
Refractive surgery is an increasingly popular procedure to decrease spectacle or contact lens dependency. The two most commonly used surgical techniques to correct myopia is Photorefractive keratectomy (PRK) and Femtosecond- Lasik (FS-LASIK)There are few publications that gathers such a long term follow up of both surgical techniques (2) Methods It has been performed a retrospective non-randomized study 509 PRK eyes and 310 FS-LASIK surgeries were followed for 10 years for the treatment of myopia and compound myopic astigmatism. Patients were followed up three months, one year, 2 years, 5 and 10 years. The safety index of both procedures was defined as a quotient between the postoperative BCVA (Best Corrected Visual Acuity) and the preoperative BCVA. The predictability is calculated as difference between the expected spherical equivalent and the achieved spherical equivalent. The efficacy index was calculated as a quotient between postoperative UCVA divided by the preoperative BCVA (3) Results. The results were: a safety index higher than 100% (109%) and an efficacy index of 82.4% after 10 years of PRK surgery in both groups. FS-LASIK was the safest surgery after 10 years and the most efficacy technique although in this case there were no statistically significant differences (4) Conclusions. All these data demonstrated better indexes for FS-LASIK
ARTICLE | doi:10.20944/preprints202007.0248.v1
Subject: Social Sciences, Econometrics & Statistics Keywords: long memory; persistence; structural change; pandemics; growth; and unemployment
Online: 12 July 2020 (08:26:52 CEST)
This paper studies long economic series to assess the long-lasting effects of pandemics. We analyze if periods of time that cover pandemics have a change in trend and persistence in growth, and in level and persistence in unemployment. We find that there is an upward trend in the persistence level of growth across the centuries. In particular, shocks originated by pandemics in recent times seem to have permanent effect in growth. Moreover, our results show that the unemployment rate increases and it becomes more persistent after a pandemic. In this regard, our findings support the design and implementation of counter-cyclical policies to soften the shock of the pandemic.
REVIEW | doi:10.20944/preprints202004.0294.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: signaling pathway; microRNA; long-noncoding RNA; chemoresistence; cervical cancer
Online: 17 April 2020 (08:12:52 CEST)
Cervical cancer is known as one of the most important cancers in women worldwide. Chemotherapy is a standard treatment for advanced/recurrent cervical cancer in which the prognosis of the disease is really poor and the 1-year survival chance in these patients is maximally 20%. However, resistance to anticancer drugs is a major problem in treating cancer. Cervical cancer stem cells are considered as a fundamental cause of chemo and radio-resistance and also relapse after primary successful treatment. Signaling pathways include a wide range of molecular mechanisms contribute to drug resistance. Recently, microRNAs (miRNAs) are announced as a group of molecular biomarkers involving in response to chemotherapy in cancer patients. As the miRNAs, there are some long non-coding RNAs (LncRNAs) which their aberrant expression is considered as a biomarker for monitoring chemoresistance. In this review, we summarized current reports about the involvement of signaling pathways during chemoresistance in cervical cancer. Then, genes that have been demonstrated their involvement during drug resistance in cervical cancer were tabulated. Further, miRNAs that have been reported as biomarkers during treatment are listed. By bioinformatic analysis, we predictedmiR-335-5p and miR-16-5p as the most potential biomarkers for monitoring resistance to chemotherapy. Finally, long non-coding RNAs that have been introduced in recent studies as novel biomarkers during the response to chemotherapy were mentioned.
ARTICLE | doi:10.20944/preprints201910.0183.v1
Subject: Mathematics & Computer Science, Probability And Statistics Keywords: ARDL; Inflation; Interest; Long-run; RGDPPC; Short-run; Unemployment
Online: 16 October 2019 (09:40:00 CEST)
Research background: Relationship between inflation rate, unemployment rate, interest rate and real gross domestic product per capita in Nigeria. However, there seems to be a short-run or long-run relationship among the macroeconomic variables.Purpose: This study investigated the impact of the inflation rate, unemployment rate and interest rate on real gross domestic product per capita (RGDPPC) (proxy for economic growth) and proffered recommendations towards enhancing economic growth and to reduce the distasteful effects of inflation rate, unemployment rate and interest rate in Nigeria in this present time economic challenges.Research methodology: This study applied a linear dynamic model Autoregressive Distributed Lag (ARDL) modeling technique to analyze the short-run dynamics and long-run relationship of the economic growth in Nigeria over the sample period between 1984 and 2017 using annual secondary data extracted from World Bank Development Indicators Report (last updated January 2019).Results: The empirical results showed that there was long-run relationship between inflation rate, unemployment rate and interest rate on real gross domestic product per capita (proxy for economic growth) in Nigeria. The result further revealed that only unemployment rate had a significant positive impact on real gross domestic product per capita in the long-run and inflation rate had a significant negative impact on real gross domestic product per capita in the short-run.Novelty: Therefore, the study concluded that unemployment rate and inflation rate proved to have significant impacts on economic growth in the long-run and short-run respectively. Formulation of policies to reduce unemployment through the adoption of labour concentrated technique of production, entrepreneurship development and policy to keep the inflation rate at single digit.
ARTICLE | doi:10.20944/preprints201806.0166.v1
Subject: Engineering, Civil Engineering Keywords: deformation monitoring; distributed monitoring; single-cell box girder; long-gage strain; long-gage Fiber Bragg Grating; strain distribution; shear lag effect; shear action
Online: 12 June 2018 (05:47:08 CEST)
Distributed deformation based on Fiber Bragg Grating sensors or other kinds of strain sensors can be used to evaluate safety in operating periods of bridges. However, most of the published researches about distributed deformation monitoring are focused on solid rectangular beam rather than box girder—a kind of typical hollow beam widely employed in actual bridges. Considering that the entire deformation of a single-cell box girder contains not only bending deflection but also two additional deformations respectively caused by shear lag and shearing action, this paper again revises the improved conjugated beam method (ICBM) based on the LFBG sensors to satisfy the requirements for monitoring two mentioned additional deformations. The best choice for the LFBG sensor placement in box gilder is also proposed in this paper due to strain fluctuation on flange caused by shear lag effect. Results from numerical simulations show that most of the theoretical monitoring errors of the revised ICBM are 0.3%~1.5%, and the maximum error is 2.4%. A loading experiment for a single-cell box gilder monitored by LFBG sensors show that most of the practical monitoring errors are 6%~8%, and the maximum error is 11%.
ARTICLE | doi:10.20944/preprints202205.0191.v1
Subject: Biology, Physiology Keywords: repolarization variability; beat-to-beat; entropy; delayed repolarization; long QT
Online: 13 May 2022 (10:44:15 CEST)
Previous studies have quantified repolarization variability using time-domain, frequency-domain and non-linear analysis in mouse hearts. Here, we investigated the relationship between these parameters and ventricular arrhythmogenicity in a hypokalaemia model of acquired long QT syndrome. Methods: Left ventricular monophasic action potentials (MAPs) were recorded during right ventricular regular 8 Hz pacing during normokalaemia (5.2 mM [K+]), hypokalaemia modelling LQTS (3 mM [K+]) or hypokalaemia with 0.1 mM heptanol in Langendorff-perfused mouse hearts. Results: During normokalaemia, mean APD was 33.5±3.7 ms. Standard deviation (SD) of APDs was 0.63±0.33 ms, coefficient of variation was 1.9±1.0% and the root mean square (RMS) of successive differences in APDs was 0.3±0.1 ms. Low- and high-frequency peaks were 0.6±0.5 and 2.3±0.7 Hz, respectively, with percentage powers of 38±22 and 61±23%. Poincaré plots of APDn+1 against APDn revealed ellipsoid morphologies with SD along the line-of-identity (SD2) to SD perpendicular to the line-of-identity (SD1) ratio of 4.6±1.1. Approximate and sample entropy were 0.49±0.12 and 0.64±0.29, respectively. Detrended fluctuation analysis revealed short- and long-term fluctuation slopes of 1.62±0.27 and 0.60±0.18, respectively. Hypokalaemia provoked ventricular tachycardia in six of seven hearts, prolonged APDs (51.2±7.9 ms), decreased SD2/SD1 ratio (3.1±1.0), increased approximate and sample entropy (0.68±0.08 and 1.02±0.33) and decreased short-term fluctuation slope (1.23 ± 0.20) (ANOVA, P<0.05). Heptanol prevented VT in all hearts studied without further altering the above repolarization parameters observed during hypokalaemia. Conclusion: Reduced SD2/SD1, increased entropy and decreased short-term fluctuation slope are associated with ventricular arrhythmogenesis in hypokalaemia. Heptanol exerts anti-arrhythmic effects without affecting repolarization variability.
ARTICLE | doi:10.20944/preprints202202.0051.v1
Subject: Life Sciences, Other Keywords: Glioblastoma; survival prediction; Machine Learning; biomarkers; HumanPSDTM; Long-term survivor
Online: 3 February 2022 (12:00:23 CET)
Glioblastoma (GBM) is a very aggressive malignant brain tumor with the vast majority of patients surviving less than 12 months (Short-term survivors [STS]). Only around 2% of patients survive more than 36 months (Long-term survivors [LTS]). Studying these extreme survival groups might help in better understanding GBM biology. This work aims at exploring application of machine learning methods in predicting survival groups(STS, LTS). We used age and gene expression profiles belonging to 249 samples from publicly available datasets. 10 Machine learning methods have been implemented and compared for their performances. Hyperparameter tuned random forest model performed best with accuracy of 80% (AUC of 74% and F1_score of 85%). The performance of this model is validated on external test data of 16 samples. The model predicted the true survival group for 15 samples achieving an accuracy of 93.75%. This classification model is deployed as a web tool GlioSurvML. The top 1500 features which retained classification efficiency (Accuracy of 80%, AUC of 74%) were studied for enriched pathways and disease-causal biomarker associations using the HumanPSDTM database. We identified 199 genes as possible biomarkers of GBM and/or similar diseases (like Glioma, astrocytoma, and others). 57 of these genes are shown to be differentially expressed across survival groups and/or have impact on survival. This work demonstrates the application of machine learning methods in predicting survival groups of GBM.
ARTICLE | doi:10.20944/preprints202112.0052.v1
Subject: Engineering, Civil Engineering Keywords: acoustic emission; long-range correlations; natural time analysis; heterogeneous materials
Online: 3 December 2021 (11:37:56 CET)
This work focuses on analyzing acoustic emission (AE) signals as a means to predict failure in structures. Two main approaches are considered: (i) long-range correlation analysis using both the Hurst (H) and the Detrended Fluctuation Analysis (DFA) exponents, and (ii) natural time domain (NT) analysis. These methodologies are applied to the data collected from two application examples: a glass fiber reinforced polymeric plate and a spaghetti bridge model, where both structures were subjected to increasing loads until collapse. A traditional (AE) signal analysis is also performed to reference the study of the other methods. Results indicate that the proposed methods yield a reliable indication of failure in the studied structures.
ARTICLE | doi:10.20944/preprints202108.0195.v1
Subject: Life Sciences, Virology Keywords: vesicular stomatitis virus; IVV, transcriptome; nanopore sequencing; long-read sequencing
Online: 9 August 2021 (12:44:21 CEST)
Indiana Vesiculovirus (IVV; formerly as Vesicular stomatitis virus and Vesicular stomatitis Indiana virus) causes a disease in livestock that is very similar to the foot and mouth disease thereby an outbreak may lead to significant economic loss. Long-read sequencing (LRS) -based approaches revealed a hidden complexity of the transcriptomes in several viruses already. This technique was utilized already for the sequencing of the IVV genome, but our study is the first for the application of this technique for the profiling of IVV transcriptome. Since LRS is able to sequence full-length RNA molecules, and thereby providing more accurate annotation of the transcriptomes than the traditional short-read sequencing methods. The objectives of this study were to assemble the complete transcriptome of using nanopore sequencing, to ascertain cell-type specificity and dynamics of viral gene expression and to evaluate host gene expression changes induced by the viral infection. We carried out a time-course analysis of IVV gene expression in human glioblastoma and primate fibroblast cell lines using a nanopore-based LRS approach and applied both amplified and direct cDNA sequencing, as well as cap-selection for a fraction of samples. Our investigations revealed that, although the IVV genome is simple, it generates a relative complex transcriptomic architecture. In this study, we also demonstrated that IVV transcripts vary in structure and exhibit differential gene expression patterns in the two examined cell types.
ARTICLE | doi:10.20944/preprints202107.0252.v1
Online: 12 July 2021 (12:03:06 CEST)
Deep neural networks (DNNs) have made a huge impact in the field of machine learning by providing unbeatable humanlike performance to solve real-world problems such as image processing and natural language processing (NLP). Convolutional neural network (CNN) and recurrent neural network (RNN) are two typical architectures that are widely used to solve such problems. Time sequence-dependent problems are generally very challenging, and RNN architectures have made an enormous improvement in a wide range of machine learning problems with sequential input involved. In this paper, different types of RNN architectures are compared. Special focus is put on two well-known gated-RNN’s Long Term Short Memory (LSTM) and Gated Recurrent Unit (GRU). We evaluated these models on the task of force estimation system in pouring. In this study, four different models including multi-layers LSTM, multi-layers GRU, single-layer LSTM and single-layer GRU) were created and trained. The result suggests that multi-layer GRU outperformed other three models.
ARTICLE | doi:10.20944/preprints202002.0177.v3
Subject: Mathematics & Computer Science, Algebra & Number Theory Keywords: bias; simulation; long-term monitoring; Delta Smelt; San Francisco Estuary
Online: 23 June 2021 (11:50:11 CEST)
In fisheries monitoring, catch is assumed to be a product of fishing intensity, catchability, and availability, where availability is defined as the number or biomass of fish present and catchability refers to the relationship between catch rate and the true population. Ecological monitoring programs use catch per unit of effort (CPUE) to standardize catch and monitor changes in fish populations; however, CPUE is proportional to the portion of the population that is vulnerable to the type of gear that is used in sampling, which is not necessarily the entire population. Programs often deal with this problem by assuming that catchability is constant, but if catchability is not constant, it is not possible to separate the effects of catchability and population size using monitoring data alone. This study uses individual-based simulation to separate the effects of changing environmental conditions on catchability and availability in environmental monitoring data. The simulation combines a module for sampling conditions with a module for individual fish behavior to estimate the proportion of available fish that would escape from the sample. The method is applied to the case study of the well-monitored fish species Delta Smelt (Hypomesus transpacificus) in the San Francisco Estuary, where it has been hypothesized that changing water clarity may affect catchability for long-term monitoring studies. Results of this study indicate that given constraints on Delta Smelt swimming ability, it is unlikely that the apparent declines in Delta Smelt abundance are due to an effect of changing water clarity on catchability.
ARTICLE | doi:10.20944/preprints202105.0722.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Dementia; multicomponent training; long-term care home; social ethical approach
Online: 31 May 2021 (09:45:37 CEST)
Multicomponent training is recommended for people with dementia living in long-term care homes. Nevertheless, evidence is limited and people with severe dementia are often excluded from trials. Hence, the aim of this study was to investigate (1) the feasibility and (2) the requirements regarding a multicomponent training for people with moderate to severe dementia. The study was conducted as an uncontrolled single arm pilot study with a mixed methods approach. 15 nursing home residents with a mean age of 82 years (range: 75-90 years; female: 64%) with moderate to severe dementia received 16 weeks of multicomponent training. Feasibility and requirements of the training were assessed by a standardized observation protocol. Eleven participants regularly attended the intervention. The highest active participation was observed during gait exercises (64%), the lowest during strength exercises (33%). It was supportive if exercises were task-specific or related to everyday life. This study confirms that a multicomponent training for the target group is (1) feasible and well accepted. To enhance active participation (2) individual instructions and the implementation of exercises related to everyday life is required. The effectiveness of the adapted training should be tested in future randomized controlled trials.
ARTICLE | doi:10.20944/preprints202104.0765.v1
Subject: Life Sciences, Biochemistry Keywords: ribosome biogenesis; rRNA processing; RNase MRP; long/short 5.8S rRNA
Online: 29 April 2021 (07:54:07 CEST)
Processing of the RNA polymerase I pre-rRNA transcript into the mature 18S, 5.8S, and 25S rRNAs requires removing the “spacer” sequences. The canonical pathway for the removal of the ITS1 spacer, located between 18S and 5.8S rRNAs in the primary transcript, involves cleavages at the 3’ end of 18S rRNA and at two sites inside ITS1. The process generates a long and a short 5.8S rRNA that differ in the number of ITS1 nucleotides retained at the 5.8S 5’ end. Here we document a novel pathway that generates the long 5.8S for ITS1 while bypassing cleavage within ITS1. It entails a single endonuclease cut at the 3’-end of 18S rRNA followed by exonuclease Xrn1 degradation of ITS1. Mutations in RNase MRP increase the accumulation of long relative to short 5.8S rRNA; traditionally this is attributed to a decreased rate of RNase MRP cleavage at its target in ITS1, called A3. In contrast, we report here that the MRP induced switch between long and short 5.8S rRNA formation occurs even when the A3 site is deleted. Based on this and our published data, we propose that the switch may depend on RNase MRP processing RNA molecules other than pre-rRNA.
ARTICLE | doi:10.20944/preprints202102.0325.v1
Subject: Biology, Anatomy & Morphology Keywords: Hazel Grouse; Bohemian Forest; Long-Term Monitoring; Population Trend; TRIM.
Online: 16 February 2021 (13:33:25 CET)
The population dynamics of Hazel Grouse was studied by presence/ absence recording at stationary sites along fixed routes (110 km) during 1972-2019 in the central part of the Bohemian Forest (Šumava, Czech Republic). The 100-km² study area covered altitudes between 600 m (Rejstejn) and 1,253 m a.s.l., (mount Sokol). Our data base contained indices of Hazel Grouse occupancy: positive sites/ controlled sites for a yearly increasing number of Hazel Grouse occurrence sites (N = 134) for 48 years. We used a loglinear Poisson-regression method to analyze the long-term population trend for Hazel Grouse in the study area. In the period 1972 to 2006 we found a stable Hazel Grouse population (p = 0.83). From 2006-2007 to 2019, the population index dropped (-3.8% per year, p < 0.05) for the last 13 years. This decline is assumed to be influenced by habitat loss due to succession resulting in older, more open forest stands, by strongly increasing forestry and windstorm “Kyrill” followed by clear cutting, bark-beetle damage, and removal of pioneer trees in spruce plantations, which diminished buds and catkins, the dominant winter food. The influence of disturbance by increasing touristic activities and/or predation is discussed. Our results could help to optimize conservation efforts for Hazel Grouse in the Bohemian Forest.
ARTICLE | doi:10.20944/preprints202012.0561.v2
Subject: Materials Science, Biomaterials Keywords: polyethylene; blend; long-chain branch; thermorheological complexity; activation energy spectrum
Online: 22 January 2021 (13:06:37 CET)
Long-chain branched metallocene-catalyzed high-density polyethylenes (LCB-mHDPE) were solution blended to obtain blends with varying degrees of branching. A high molecular LCB-mHDPE was mixed with low molecular LCB-mHDPE are varying concentrations, whose rheological behavior is similar but whose molar mass and molar mass distribution is significantly different. Those blends were characterized rheologically to study the effects of concentration, molar mass distribution, and long-chain branching level of the low molecular LCB-mHDPE. Owing to the ultra-long relaxation times of the high molecular LCB-mHDPE, the blends started behaving clearly more long-chain branched than the base materials. The thermorheological complexity showed an apparent increase in the activation energies Ea determined from G’, G”, and especially δ. Ea(δ), which for LCB-mHDPE is a peak function, turned out to produce even more pronounced peaks than observed for regular LCB-mPE and also LCB-mPE with broader molar mass distribution. Thus, it is possible to estimate the molar mass distribution from the details of the thermorheological complexity.
ARTICLE | doi:10.20944/preprints202012.0310.v1
Subject: Life Sciences, Biochemistry Keywords: Variola major; phylogeographical analysis; long-term calibrations; short- term calibrations
Online: 14 December 2020 (09:21:34 CET)
In order to reconstruct the origin and pathways of variola virus (VARV) dispersion, we analyzed 47 VARV isolates available in public databases and their SNPs. The mean substitution rate of the whole genomes was 9.41x10-6 (95%HPD:8.5-11.3x10-6) substitutions/site/year. The time of the tree root was estimated to be a mean 68 years (95%HPD:60.5–75.9). The phylogeographical analysis showed that the Far East and India were the most probable locations of the tree root and of the inner nodes, respectively, whereas for the outer nodes it corresponded to the sampling locations. The Bayesian Skyline plot showed that the effective number of infections started to grow exponentially in 1915-1920, peaked in the 1940s, and then decreased to zero. Our results suggests that the VARV major strains circulating between 1940s-1970s probably shared a common ancestor originated in the Far East; subsequently moved to India, which became the center of its dispersion to eastern and southern Africa, and then to central Africa and the Middle East, probably following the movements of people between south-eastern Asia and the other places with a common colonial history. These findings may help to explain the controversial reconstructions of the history of VARV obtained using long- and short- term calibrations.
CASE REPORT | doi:10.20944/preprints201908.0278.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: FOLFIRINOX; pancreatic ductal adenocarcinoma; surgery; liver metastases; long term survival
Online: 27 August 2019 (05:16:03 CEST)
Metastatic pancreatic ductal adenocarcinoma pancreatic (PDAC) is characterized by poor prognosis and short survival. Today, the use of new polytherapeutic regimens increases clinical outcome of these patients opening new clinical scenario. A crucial issue related to the actual improvement achieved with these new regimens is represented by the occasional possibility to observe a radiological complete response of metastatic lesions in patients with synchronous primary tumor. What could be the best therapeutic management of these patients? Could surgery represent an indication? Herein we reported a case of a patient with a PDAC of the head with multiple liver metastasis, who underwent first line chemotherapy with mFOLFIRINOX. After 10 cycles, he achieved a complete radiological response of liver metastases and a partial response of pancreatic lesion. A, duodenocephalopancreasectomy was performed. Due to liver a lung metastases after 8 months from surgery, a second line therapy was started with a disease free survival and overall survival of 8 months and 45 months, respectively. Improvement in the molecular characterization of PDAC could help in the selection of patients suitable for multimodal treatments.
ARTICLE | doi:10.20944/preprints201905.0034.v1
Subject: Biology, Entomology Keywords: long-term; sex ratio; action threshold; pest management; insecticide use
Online: 6 May 2019 (08:19:10 CEST)
A long-term investigation of D. suzukii dynamics in wild blueberry fields from 2012 - 2018 demonstrates relative abundance is still increasing seven years after initial invasion. Relative abundance is determined by physiological date of first detection and air temperatures the previous winter. Date of first detection of flies does not determine date of fruit infestation. The level of fruit infestation is determined by year, fly pressure, and insecticide application frequency. Frequency of insecticide application is determined by production system. Non-crop wild fruit and predation influences fly pressure; increased wild fruit abundance results in increased fly pressure. Increased predation rate reduces fly pressure, but only at high abundance of flies, or when high levels of wild fruit are present along field edges. Male sex ratio might be declining over the seven years. Action thresholds were developed from samples of 92 fields from 2012 - 2017 that related cumulative adult male trap capture to the following week likelihood of fruit infestation. A two-parameter gamma density function describing this probability was used to develop a risk-based gradient action threshold system. The action thresholds were validated from 2016-2018 in 35 fields and were shown to work well in two of three years (2016 and 2017).
Subject: Life Sciences, Genetics Keywords: mucosal melanoma; dogs; transcriptome sequencing; long non-coding RNAs (lncRNAs)
Online: 3 May 2019 (13:59:22 CEST)
Mucosal melanomas (MM) are rare aggressive cancers in humans and one of the most common forms of oral cancers in dogs. Similar biological and histological features are shared between MM in both species making dogs a powerful model for comparative oncology studies of melanomas. Although exome sequencing recently identified recurrent coding mutations in canine MM, little is known about changes in non-coding gene expression and more particularly in canine long non-coding RNAs (lncRNAs), which are commonly dysregulated in human cancers. Here, we sampled a large cohort (n= 52) of canine normal/tumor oral MM from three predisposed breeds (poodles, Labrador retrievers and golden retrievers) and used deep transcriptome sequencing to identify more than 400 differentially expressed (DE) lncRNAs. We further prioritized candidate lncRNAs by comparative genomic analysis to pinpoint 26 dog-human conserved DE lncRNAs, including SOX21-AS, ZEB2-AS and CASC15 lncRNAs. Using unsupervised co-expression networks analysis with coding genes, we inferred potential functions of DE lncRNAs suggesting associations with cancer-related genes, cell cycle and carbohydrate metabolism GO terms. Finally, we exploited our multi-breed design to identify DE lncRNAs per breed. This study provides a unique transcriptomic resource for studying oral melanoma in dogs and highlights lncRNAs that may potentially be diagnostic or therapeutic targets for human and veterinary medicine.
ARTICLE | doi:10.20944/preprints201808.0105.v1
Subject: Life Sciences, Other Keywords: depression; total protein; elder people; physical function; long-term care
Online: 6 August 2018 (09:41:35 CEST)
Due to its devastating consequences, late life depression is an important public health problem. The aim of the study was the analysis of variables which may potentially influence risk of depression (GDS-SF). Furthermore, the aim was to study possible mediating effect of given variables on the relationship between the total protein concentration and risk of depression in older-adults with chronic diseases, and physical function impairment. The research sample included a total of 132 older adults with chronic conditions and physical function impairments, remaining under a long-term care in residential environment. Negative linear correlation was observed between patients’ physical functionality, total protein concentration, concentration of HDL cholesterol, arm circumference, and the risk of depression. Considerably stronger relationship was observed between total protein concentration, and GDS-SF, in elderly suffering from sensory dysfunction (b = −6.42, 95% CI = −11.27; −1.58). The effect of the mediation between depression risk is correlated to total protein concentration in blood serum, and the mediators are probably low function impairment and low levels of 25 (OH)D vitamin. Cohort control research is suggested to confirm the hypothesis.
ARTICLE | doi:10.20944/preprints201806.0295.v1
Subject: Behavioral Sciences, Other Keywords: long-term care, elderly people, behavior assessment, factor analysis, independence
Online: 19 June 2018 (10:59:03 CEST)
The rapid growth rate of the elderly population is a serious current issue in most countries, affecting them economically through needed medical treatment and healthcare planning. The priority concern is how to reduce the number of elderly people requiring long-term healthcare and raise the number who are able to live independently. This study executed a behavior assessment of elderly person’s self-reported use of electric scooters and analyzed their degree of acceptance of these assisted living tools, partly through a related factor analysis of our survey instrument. We used this questionnaire survey as our research method, applying SPSS22 software for factor analysis that revealed five survey facets.
ARTICLE | doi:10.20944/preprints201607.0004.v1
Subject: Social Sciences, Econometrics & Statistics Keywords: Bayesian modeling, long memory/anti-persistence; continuous time modeling; MCMC
Online: 4 July 2016 (09:57:31 CEST)
Using recent developments in econometrics and computational statistics we consider the estimation of the instantaneous rate of asset return process when the underlying Data Generating Mechanism (DGM) is an Ornstein-Uhlenbeck process, driven by fractional noise, and sampled at fixed intervals of length h. To address the problem we adopt throughout the paper an exact discretization approach. This enable us to exploit the fact that a flow sampling scheme arises naturally when observing the DGM. For, while the instantaneous rate of return process is unobservable at points in time, its time integral over successive observations is observable since it equals the increment of log-prices. Exact discretization delivers an ARIMA(1,1,1) model for log-prices with a fractional driving noise. Building on the resulting exact discretization formulae and covariance function, a new Markov Chain Monte Carlo (MCMC) scheme is proposed and we examine the properties of both the time and frequency domain likelihoods / posteriors through Monte Carlo. For the exact discrete model we adopt a general sampling interval of length h. This allow us to determine the optimal choice of h independent of the sample size. An empirical application using high frequency stock price data is presented showing the relevance of aggregation over time issues in modelling asset prices.
ARTICLE | doi:10.20944/preprints202106.0104.v1
Subject: Earth Sciences, Atmospheric Science Keywords: hydrological research basin; precipitation; temperature; long-term trends; climate change; evapotranspiration
Online: 3 June 2021 (11:35:58 CEST)
While the ongoing climate change is well documented, the impacts exhibit a substantial variability, both in direction and magnitude, visible even at regional and local scales. However, the knowledge of regional impacts is crucial for the design of mitigation and adaptation measures, particularly when changes in the hydrological cycle are concerned. In this paper we present hydro-meteorological trends based on observations from a hydrological research basin in Eastern Austria between 1979-2019. The analysed state variables include the air temperature, the precipitation, and the catchment runoff. Additionally, trends for the catchment evapotranspiration were derived. The analysis shows that while the mean annual temperature was decreasing and annual temperature minima remained constant, the annual maxima were rising. The long-term trends indicate a shift of precipitation to the summer with minor variations observed for the remaining seasons and at an annual scale. Observed precipitation intensities mainly increased in spring and summer between 1979-2019. The catchment evapotranspiration, computed based on catchment precipitation and outflow, showed an increasing trend for the observed time period.
ARTICLE | doi:10.20944/preprints202105.0322.v1
Subject: Biology, Anatomy & Morphology Keywords: Virus; plant virus; long noncoding RNA; replication; positive sense RNA virus
Online: 14 May 2021 (11:01:56 CEST)
Long noncoding RNAs (lncRNAs) of virus origin accumulate in cells infected by many positive strand (+) RNA viruses to bolster viral infectivity. Their biogenesis mostly utilizes exoribonucleases of host cells that degrade viral genomic or subgenomic RNAs in the 5’-to-3’ direction until being stalled by well-defined RNA structures. Here we report a viral lncRNA that is produced by a novel replication-dependent mechanism. This lncRNA corresponds to the last 283 nucleotides of the turnip crinkle virus (TCV) genome, hence is designated tiny TCV subgenomic RNA (ttsgR). ttsgR accumulated to high levels in TCV-infected Nicotiana benthamiana cells when the TCV-encoded RNA-dependent RNA polymerase (RdRp), also known as p88, was overexpressed. Both (+) and (-) strand forms of ttsgR were produced in these cells in a manner dependent on the RdRp functionality. Strikingly, templates as short as ttsgR itself were sufficient to program ttsgR amplification, as long as the TCV-encoded replication proteins, p28 and p88, were provided in trans. Consistent with its replicational origin, ttsgR accumulation required a 5’ terminal G3(A/U)4 motif shown by others to be crucial for the replication of a TCV satellite RNA. More importantly, introducing a new G3(A/U)4 motif elsewhere in the TCV genome was alone sufficient to cause the emergence of another lncRNA. Collectively our results unveil a replication-dependent mechanism for the biogenesis of viral lncRNAs, thus suggesting that multiple mechanisms, individually or in combination, may be responsible for viral lncRNA production.
ARTICLE | doi:10.20944/preprints202102.0401.v1
Subject: Engineering, Automotive Engineering Keywords: Machine learning; Ultrasonic measurements; Long Short-Term Memory; Industrial Digital technologies
Online: 18 February 2021 (09:31:43 CET)
Beer fermentation is typically monitored by periodic sampling and off-line analysis. In-line sensors would remove the need for time-consuming manual operation and provide real-time evaluation of the fermenting media. This work uses a low-cost ultrasonic sensor combined with machine learning to predict the alcohol concentration during beer fermentation. The highest accuracy model (R2=0.952, MAE=0.265, MSE=0.136) used a transmission-based ultrasonic sensing technique along with the measured temperature. However, the second most accurate model (R2=0.948, MAE=0.283, MSE=0.146) used a reflection-based technique without the temperature. Both the reflection-based technique and the omission of the temperature data are novel to this research and demonstrate the potential for a non-invasive sensor to monitor beer fermentation.
ARTICLE | doi:10.20944/preprints202101.0512.v1
Subject: Biology, Anatomy & Morphology Keywords: fish; functional data analysis; long-term monitoring; habitat; occupancy; modeling; California
Online: 25 January 2021 (15:11:52 CET)
Abundance of estuarine fish species has declined globally. In the San Francisco Estuary (SFE), long-term monitoring documented declines of many species including the anadromous species Longfin Smelt (Spirinchus thaleichthys). To improve management and recovery planning, we identified patterns in the timing, seasonal occupancy, and distribution of Longfin Smelt in a monitoring study (San Francisco Bay Study) for five regions of the SFE using a generalized additive model. We then investigated the year-to-year variability in the shape of the seasonal relationships using functional data analysis (FDA). FDA separated the variability due to population size from variability due to differences in occupancy timing. We found that Longfin Smelt have a consistent seasonal distribution pattern, that two trawl types were needed to accurately describe the pattern, and that the pattern is largely consistent with the hypothesized conceptual model. After accounting for variability in occupancy due to year-class strength, the timing of occupancy has shifted in three regions. The most variable period for the upstream regions Suisun Bay and Confluence was age-0 summer and for the downstream region Central Bay, was age-0 late fall. This manifested as a recent delay in the typical fall re-occupation of upstream regions, reducing Longfin Smelt abundance as calculated by another monitoring study (Fall Midwater Trawl); thus, a portion of recent reductions in Fall Midwater Trawl abundance of Longfin Smelt result from changes in behavior rather than a decline in abundance. The presence of multiple monitoring surveys allowed analysis of distribution from one data set to interpret patterns in abundance of another. Future investigations will examine environmental conditions as covariates during these periods and could improve our understanding of what conditions contribute to the shifting occupancy timing of Longfin Smelt, and possibly provide insight into the long-term quality of the San Francisco Estuary as habitat.
ARTICLE | doi:10.20944/preprints202012.0616.v1
Subject: Life Sciences, Virology Keywords: pseudorabies virus; herpesvirus; transcriptome; Pacific Biosciences; nanopore sequencing; long-read sequencing
Online: 24 December 2020 (11:30:22 CET)
In the last couple of years, the implementation of long-read sequencing (LRS) technologies for transcriptome profiling has uncovered an extreme complexity of viral gene expression. In this study, we carried out a systematic analysis on the pseudorabies virus transcriptome by combining our current data obtained by using Pacific Biosciences Sequel and Oxford Nanopore Technologies MinION sequencings with our earlier data generated by other LRS and short-read sequencing techniques. As a result, we identified a number of novel genes, transcripts, and transcript isoforms, including splice and length variants, and also confirmed earlier annotated RNA molecules. One of the major findings of this study is the discovery of a large number of 5’-truncated putative mRNAs embedded into larger host mRNAs. A large fraction of these RNA molecules contain in-frame ORFs, which may encode N-terminally truncated polypeptides. These study demonstrates that the PRV transcriptome is much more complex than previously appreciated.
ARTICLE | doi:10.20944/preprints202010.0157.v1
Subject: Earth Sciences, Atmospheric Science Keywords: PM2.5; biomass burning; long-range transport of PM2.5; Source of PM2.5
Online: 7 October 2020 (11:23:14 CEST)
This paper aims to investigate the airflow that can transport emission sources of PM2.5 from neighboring countries to contribute to air pollution in northern Thailand. We applied the coupled atmospheric and air pollution model which is based on the Weather Research and Forecasting Model (WRF) and a Hybrid Single-Particle Lagrangian Integrated Trajectory Model (HYSPLIT). The model output was compared to the ground-based measurement from the Pollution Control Department (PCD) to examine model performance. As a result of model evaluation, the meteorological variables fairly agreed well compared to observation with Index of Agreement (IOA) in ranges of 0.57 to 0.79 for temperature and 0.32 to 0.54 for wind speed, while the fractional bias of temperature and wind speed were 1.3 to 2.5 °C and 1.2 to 2.1 m/s. Burma was a country that contributed much of hotpot locations by 37% of the entire hotspot locations of Southeast Asia in March. The influence of the Asian Monsoon can bring pollutants from neighboring countries such as Burma and Laos toward northern Thailand in March that likely contribute to high concentrations of PM2.5 in northern Thailand.
ARTICLE | doi:10.20944/preprints202008.0629.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: Community Health Survey; CHS; PM10 long-term effect; young adults; BMI
Online: 28 August 2020 (09:26:19 CEST)
Background: The associations between long-term exposure to particulate matters (PM) in residential ambiance and obesity are comparatively less elucidated among young adults. Methods: Using 2017 Community Health Survey data with aged 19−29 participants in 25 communities, Seoul, the relationship between obesity and long−term PM10 levels of living district was examined. We defined obesity as overweight (25≤BMI<30) or obese (30≤BMI) using Body Mass Index (BMI) from self-reported anthropometric information. Analysis was conducted sampling weighted logistic regression models by fitting municipal PM10 levels according to individual residence periods with 10 years and more residing in a current municipality. Socio-demographic factors were adjusted over all models and age−specific effect was explored among aged 19–24 and 25–29. Results: Total study population are 3,655 [men 1,680 (46.0%) and aged 19–24 1,933 (52.9%)] individuals. Among the communities with greater level of PM10; 2001–2005, associations with obesity were increased for overall with residence period; 10 years ≤ [Odds ratio, OR 1.071, 95% Confidence interval (CI) 0.969–1.185], 15 years ≤ [OR 1.118, 95% CI 1.004–1.245], and 20 years ≤ [OR 1.156, 95% CI 1.032–1.294]. However, decreased associations were detected for PM10; 2006–2010, and age–specific effects were modified according to the residence period. Conclusions: Although currently PM10 levels are decreasing, higher levels of PM10 exposure at the residential area during the earlier life-time may contribute in increasing obesity among young adults.
ARTICLE | doi:10.20944/preprints202007.0719.v1
Subject: Biology, Other Keywords: SARS-CoV-2; long-term; neutralization antibody; lymphocyte functionality; viral pathogenicity.
Online: 30 July 2020 (12:16:21 CEST)
COVID-19 patients can recover with a median SARS-CoV-2 clearance of 20 days post initial symptoms (PIS). However, we observed some COVID-19 patients with existing SARS-CoV-2 for more than 50 days PIS. This study aimed to investigate the cause of viral clearance delay and the infectivity in these patients. Demographic data and clinical characteristics of 22 long-term COVID-19 patients were collected. SARS-CoV-2 nucleic acid, peripheral lymphocyte count, and functionality were assessed. SARS-CoV-2-specific and neutralization antibodies were detected, followed by virus isolation and genome sequencing. The median age of the studied cohort was 59.83±12.94 years. All patients were clinically cured after long-term SARS-CoV-2 infection ranging from 53 to 112 days PIS. Peripheral lymphocytes counts were normal. Interferon gamma (IFN-ƴ)-generated CD4+ and CD8+ cells were normal as 24.68±9.60% and 66.41±14.87%. However, the number of IFN-ƴ-generated NK cells diminished (58.03±11.78%). All patients presented detectable IgG, which positively correlated with mild neutralizing activity (ID50=157.2, P=0.05). SARS-CoV-2 was not isolated, and a cytopathic effect was lacking. Only three synonymous variants were identified in spike protein coding regions. In conclusion, decreased IFN-γ production by NK cells and low neutralizing antibodies might favor SARS-CoV-2 long-term existence. Further, low viral load and weak viral pathogenicity was observed in COVID-19 patients with long-term SARS-CoV-2 infection.
BRIEF REPORT | doi:10.20944/preprints201912.0009.v1
Subject: Social Sciences, Economics Keywords: Great Recession; health care expenditures; long-term; convergence analysis; Phillips-Sul
Online: 2 December 2019 (10:15:40 CET)
This paper examines whether the Great Recession has altered the disparities of the US regional health care expenditures. We test the null hypothesis of convergence for the US real per capita health expenditure for the period 1980-2014. Our results indicate that the null hypothesis of convergence is clearly rejected for the total sample as well as for the pre-Great Recession period. Thus, no changes are found in this regard. However, we find that the Great Recession has modified the composition of the estimated convergence clubs, offering a much more concentrated picture in 2014 than in 2008, with most of the states included in a big club, and only 5 (Nevada, Utah, Arizona, Colorado and Georgia) exhibiting a different pattern of behavior. These two estimated clubs diverge and, consequently, the disparities in the regional health sector have increased.
ARTICLE | doi:10.20944/preprints201908.0155.v2
Subject: Engineering, Control & Systems Engineering Keywords: Long short-term memory; Brain dynamics; Data-driven modeling; Complex systems
Online: 18 September 2019 (13:05:22 CEST)
Modeling brain dynamics to better understand and control complex behaviors underlying various cognitive brain functions are of interests to engineers, mathematicians, and physicists from the last several decades. With a motivation of developing computationally efficient models of brain dynamics to use in designing control-theoretic neurostimulation strategies, we have developed a novel data-driven approach in a long short-term memory (LSTM) neural network architecture to predict the temporal dynamics of complex systems over an extended long time-horizon in future. In contrast to recent LSTM-based dynamical modeling approaches that make use of multi-layer perceptrons or linear combination layers as output layers, our architecture uses a single fully connected output layer and reversed-order sequence-to-sequence mapping to improve short time-horizon prediction accuracy and to make multi-timestep predictions of dynamical behaviors. We demonstrate the efficacy of our approach in reconstructing the regular spiking to bursting dynamics exhibited by an experimentally-validated 9-dimensional Hodgkin-Huxley model of hippocampal CA1 pyramidal neurons. Through simulations, we show that our LSTM neural network can predict the multi-time scale temporal dynamics underlying various spiking patterns with reasonable accuracy. Moreover, our results show that the predictions improve with increasing predictive time-horizon in the multi-timestep deep LSTM neural network.
Subject: Materials Science, Other Keywords: nickel-based super-alloys; M6C; u phase; long time exposure; M12C
Online: 16 September 2019 (01:22:39 CEST)
The Ni-Co-Cr-W-Mo system is critical for the design of nickel-based super-alloys. This system stabilizes different topologically close packed (TCP) phases in many of the commercially super-alloys with high W and Mo contents. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and thermodynamic calculations are applied to investigate the thermodynamics of the precipitates in two different W content Ni-Co-Cr-W-Mo super-alloys. Computational thermodynamics verified experimental observation of the f u phase formation as a function of temperature and alloy chemistry, but the kinetics for the precipitation of M6C phase do not agree with the experimental findings. The major precipitates of alloy 1 at temperatures 700 and 750 °C during long time exposure are M23C6, γ′ phase, and MC, and alloy 2 are M23C6, γ′ phase, MC, M6C and u phase. The W addition is found to promote the precipitation of M6C and u phase during exposure. The M6C has higher W and lower Ni content than that of u phase, meanwhile, M6C is an unstable phase would transform into M12C after 5000 h exposure at 750 °C. A great quantity of needle-like u phases precipitated after exposure at 750 °C for 5000h, which have no effect on the impact property of alloy 2.
ARTICLE | doi:10.20944/preprints201810.0542.v1
Subject: Earth Sciences, Geophysics Keywords: Climate sensitivity; scale invariance; long-range persistence; climate variability; emergent constrains
Online: 23 October 2018 (15:59:17 CEST)
Earth's global surface temperature shows variability on an extended range of temporal scales and satisfies an emergent scaling symmetry. Recent studies indicate that scale invariance is not only a feature of the observed temperature fluctuations, but an inherent property of the temperature response to radiative forcing, and a principle that links the fast and slow climate responses. It provides a bridge between the decadal- and centennial-scale fluctuations in the instrumental temperature record, and the millennial-scale equilibration following perturbations in the radiative balance. In particular, the emergent scale invariance makes it possible to infer equilibrium climate sensitivity (ECS) from the observed relation between radiative forcing and global temperature in the instrumental era. This is verified in ensembles of Earth system models (ESMs), where the inferred values of ECS correlate strongly to estimates from idealized model runs. For the range of forcing data explored in this paper, the method gives best estimates of ECS between 2.3 and 3.4 K.
ARTICLE | doi:10.20944/preprints201809.0096.v1
Subject: Biology, Plant Sciences Keywords: Montiaceae; phylogeny; phylogeography; long-distance dispersal; idiosyncrasy; Principal of Evolutionary Idiosyncraticity
Online: 5 September 2018 (12:02:42 CEST)
Montiaceae comprise a clade of at least 270 species plus about 20 accepted subspecific taxa, primarily of western America and Australia. The present paper is the first of a two-part work that seeks to evaluate evolutionary theory via metadata analysis of Montiaceae. In particular, it uses metadata analysis to evaluate the theory in theory-laden methods that have been applied in evolutionary analyses of Montiaceae. This part focuses on phylogeny and phylogeography. The second part focuses on phenotypic and ecological diversification. An emergent theme in this paper is the degree to which historical idiosyncrasy during Montiaceae evolution misleads quantitative methods of evolutionary reconstruction and phylogeographic interpretation. This suggests that idiosyncraticity itself is a fundamental property of evolution. The second part of this work elaborates this notion as the Principle of Evolutionary Idiosyncraticity. The present part describes idiosyncraticity in molecular phylogenetic and phylogeographic data and uses this notion to refine ideas on Montiaceae evolution. Phylogenetic metadata conflicts and conflicting phylogeographic interpretations are discussed. I conclude that, owing to PEI, quantitative methods of evolutionary analysis cannot be globally accurate, though they are useful heuristically. In contrast, classical narrative analysis is robust in the face of PEI.
REVIEW | doi:10.20944/preprints201809.0004.v1
Subject: Life Sciences, Virology Keywords: gammaherpesviruses, long non-coding RNAs, RNA structure and function, viral pathogenesis
Online: 1 September 2018 (17:36:48 CEST)
Advances in next-generation sequencing have facilitated the discovery of a multitude of long non-coding RNAs (lncRNAs) with pleiotropic functions in cellular processes, disease and viral pathogenesis. It came as no surprise when viruses were also revealed to transcribe their own lncRNAs. Among them, gammaherpesviruses, one of the three subfamilies of the Herpesviridae, code their largest number. These structurally and functionally intricate non-coding (nc) transcripts modulate cellular and viral gene expression to maintain viral latency or prompt lytic reactivation. The lncRNAs allow the virus to escape cytosolic surveillance, sequester and re-localize essential cellular factors and modulate the cell cycle and proliferation. Some viral lncRNAs act as “messenger molecules”, transferring information about viral infection to neighboring cells. This broad range of lncRNA functions is achieved through lncRNA structure-mediated interactions with effector molecules of viral and host origin, including other RNAs, proteins and DNAs. In this review, we discuss examples of gammaherpesvirus-encoded lncRNAs, emphasize their unique structural attributes, and link them to viral life cycle, pathogenesis and disease progression. We will address their potential as novel targets for drug discovery and propose future directions to explore lncRNA structure and function relationship.
ARTICLE | doi:10.20944/preprints201711.0159.v1
Subject: Earth Sciences, Atmospheric Science Keywords: atmospheric mercury; Baltic Sea; mapping of TGM levels; long range transport
Online: 24 November 2017 (09:00:15 CET)
Mercury is a toxic pollutant emitted from both natural sources and through human activities. A global interest in atmospheric mercury has risen ever since the discovery of the Minamata disease in 1956. Properties of gaseous elemental mercury enable long range transport which can cause pollution even in pristine environments. Total gaseous mercury (TGM) was measured from winter 2016 to spring 2017 over the Baltic Sea. A Tekran 2357A mercury analyser was installed aboard the research and icebreaking vessel Oden for the purpose of continuous measurements of gaseous mercury in ambient air. Measurements were performed during a campaign along the Swedish east coast and in the Bothnian Bay near Lulea during the icebreaking season. Data was evaluated from Gothenburg using a plotting software and back trajectories for air masses were calculated. The TGM average of 1.365 ± 0.054 ng/m3 during winter and 1.288 ± 0.140 ng/m3 during spring was calculated as well as a total average of 1.362 ± 0.158 ng/m3. Back trajectories showed a possible correlation of anthropogenic sources elevating the mercury background level in some areas. There were also indications of depleted air, i.e., air with lower concentrations than average, being transported from the Arctic to northern Sweden resulting in a drop in TGM levels.
ARTICLE | doi:10.20944/preprints201709.0091.v1
Subject: Physical Sciences, Condensed Matter Physics Keywords: Hamiltonian systems; classical statistical mechanics; ensemble equivalence; long-range interacting systems
Online: 20 September 2017 (04:08:44 CEST)
We investigate the stationary and dynamic properties of the celebrated Nosé-Hoover dynamics of many-body interacting Hamiltonian systems, with an emphasis on the effect of inter-particle interactions. To this end, we consider a model system with both short- and long-range interactions. The Nosé-Hoover dynamics aims to generate the canonical equilibrium distribution of a system at a desired temperature by employing a set of time-reversible, deterministic equations of motion. A signature of canonical equilibrium is a single-particle momentum distribution that is Gaussian. We find that the equilibrium properties of the system within the Nosé-Hoover dynamics coincides with that within the canonical ensemble. Moreover, starting from out-of-equilibrium initial conditions, the average kinetic energy of the system relaxes to its target value over a size-independent timescale. However, quite surprisingly, our results indicate that under the same conditions and with only long-range interactions present in the system, the momentum distribution relaxes to its Gaussian form in equilibrium over a scale that diverges with the system size. On adding short-range interactions, the relaxation is found to occur over a timescale that has a much weaker dependence on system size. This system-size dependence of the timescale vanishes when only short-range interactions are present in the system. An implication of such an ultra-slow relaxation when only long-range interactions are present in the system is that macroscopic observables other than the average kinetic energy when estimated in the Nosé-Hoover dynamics may take an unusually long time to relax to its canonical equilibrium value. Our work underlines the crucial role that interactions play in deciding the equivalence between Nosé-Hoover and canonical equilibrium.
ARTICLE | doi:10.20944/preprints201607.0088.v2
Subject: Social Sciences, Organizational Economics & Management Keywords: joint patent application; the structure of collaboration; open innovation; long tail
Online: 29 July 2016 (06:48:53 CEST)
The way people innovate and create new ideas and bring them to the market is undergoing a fundamental change from closed innovation to open innovation. Why and how do firms perform open innovation? Firms’ open innovation is measured through the levels of firms’ joint patent applications. Next, we analyze network structures and characters of firms’ joint patent applications such as betweenness and degree centrality, structure hole, and closure. From this research, we drew conclusions as follows. First, the structure of collaboration networks has both direct and indirect effects on firms’ innovative performance. Second, in the process of joint patent applications, there is a long tail phenomenon in networks of joint patent applications. Third, the number of patents and International Patent Classification (IPC) subclasses together constitute a meaningful measure of the innovation performance of firms.
ARTICLE | doi:10.20944/preprints202210.0043.v1
Subject: Information Technology & Data Management, Mathematics & Computer Science Keywords: Commodities; Long Short-Term Memory; Machine Learning; Neural Networks; Prediction; Technical analysis
Online: 5 October 2022 (13:39:16 CEST)
This paper presents the development and implementation of a machine learning model to estimate the future price of commodities in the Brazilian market from technical analysis indicators. For this, two databases were obtained regarding the commodities sugar, cotton, corn, soybean and wheat, which were submitted to the steps of data cleaning, pre-processing and subdivision. From the pre-processed data, recurrent neural networks of the long short-term memory type were used to perform the prediction of data in the interval of 1 and 3 days ahead. These models were evaluated using mean squared error, obtaining an accuracy between 0.00010 and 0.00037 on the test data for 1 day ahead and 0.00015 to 0.00041 for 3 days ahead. However, based on the results obtained, it can be stated that the developed model obtained a good prediction performance for all commodities evaluated.
ARTICLE | doi:10.20944/preprints202107.0308.v1
Subject: Social Sciences, Accounting Keywords: Relational benefits; calculative and affective commitment; long-term orientation; multi-channel agency
Online: 13 July 2021 (12:21:34 CEST)
Our study provides guidelines on how to build long-term customer relationship in the non-contract mechanism context. More specifically, the findings show that special, social, and core benefits influence calculative commitment, and operational and special benefits influence affective commitment. This study also supports that calculative and affective commitment play a crucial role in understanding multi-channel agencies’ loyalty. In sum, this study revealed that calculative and affective commitment can be considered as partial or full mediators in the relationship between RBs (relational benefits) and loyalty. This study not only contributed to the existing SET (social exchange theory) and RBs paradigm but also provided practical implications for food distribution management.
ARTICLE | doi:10.20944/preprints202012.0809.v1
Subject: Life Sciences, Biochemistry Keywords: Long-term care; care homes; nursing homes; dementia; quality improvement; palliative care
Online: 31 December 2020 (13:16:03 CET)
Important policy developments in dementia and palliative care in nursing homes between 2010 and 2015 in Flanders, Belgium might have influenced which people die in nursing homes and how they die. We aimed to examine differences between 2010 and 2015 in the prevalence and characteristics of residents with dementia in nursing homes in Flanders, and their palliative care service use and comfort in the last week of life. We used two retrospective epidemiological studies, including 198 residents in 2010 and 183 in 2015, who died with dementia in representative samples of nursing homes in Flanders. We found a 23%-point increase in dementia prevalence (P-value<0.001), with a total of 11%-point decrease in severe to very severe cognitive impairment (P=0.04). Controlling for this difference in resident characteristics, in the last week of life, there were increases in the use of pain assessment (+20%-point; P<0.001) and assistance with eating and drinking (+10%-point; P=0.02) but no change in total comfort. The higher prevalence of dementia in nursing homes with no improvement in residents’ total comfort while dying emphasize an urgent need to better support nursing homes in improving their capacities to provide timely and high-quality palliative care services to more residents dying with dementia.
ARTICLE | doi:10.20944/preprints202012.0694.v1
Subject: Engineering, Automotive Engineering Keywords: Salt Marsh; Coastal Protection; Long Island Sound; Connecticut; Green Structures; Ecosystem based
Online: 28 December 2020 (12:08:11 CET)
Connecticut marshes, like other marshes in the world, are vulnerable to anthropogenic and climate change effects. However, assessment of current sea level rise and average marsh accretion rates in Connecticut demonstrate sea level rise is not the main vulnerable factor for salt marshes loss. The study on the feasibility of developing an ecosystem-based on two coastlines in Connecticut, Guilford and Stratford, shows that both coastlines, like other coastlines in Connecticut, have limited wave energy, which is a positive factor for marsh growth. The available data assessment represents that sediment supply is the most important parameter to guarantee the resilience and sustainability of a newly developed salt marsh system in Connecticut. In Stratford, conditions for establishing a new ecosystem seem to be better, as the fetch length is pretty small, and there is some sediment supply for the ecosystem. In Guilford, wave energy is limited, but it is more than in Stratford case. Besides, sediment availability is low and the coastline experienced considerable erosion during hurricane Sandy and has not recovered yet.
REVIEW | doi:10.20944/preprints202010.0597.v1
Subject: Keywords: monarch butterflies; Danaus plexippus; population status; conservation; long-term studies; milkweed limitation
Online: 28 October 2020 (15:32:14 CET)
There are a large number of wildlife and insect species that are in trouble on this planet, and most believe that monarch butterflies in eastern North America are too, because of the well-publicized declines of their winter colonies in central Mexico in the last 25 years. A small number of studies over the last decade have cast doubt on this claim by showing declines are not evident at other stages of the annual cycle. To determine how extensive this pattern is, I conducted an exhaustive review of peer-reviewed and grey literature on (eastern) monarch population censuses and studies, conducted across all seasons, and extracted data from these sources to evaluate how monarch abundance has or has not changed over time. I identified 20 collections of data that included butterfly club reports, compilations of citizen-science observations, migration roost censuses, long-term studies of isotopic signatures, and even museum records. These datasets range in duration from 15 years to over 100 years, and I endeavored to also update each with information from the most current years. I also re-examined the winter colony data after incorporating historical records of colony measurements dating back to 1976. This represents the most complete and up-to-date synthesis of information regarding this population. When I examined the long-term trajectory within each dataset a distinct pattern emerged. Modest declines are evident within the winter colonies (over the full 45 year dataset), and, within three censuses conducted during the spring recolonization. Meanwhile, 16 completely separate monitoring studies conducted during the summer and fall (and from varying locations) revealed either no trend at all or in fact an increase in abundance. While each of these long-term studies has inherent limitations, the fact that all 16 sources of data show the same pattern is undeniable. Moreover, this evidence is consistent with recently-conducted genetic work that shows a lack of decline. Collectively, these results indicate that despite diminishing winter colonies and spring migrations, monarchs in eastern North America are capable of rebounding fully each year, implying that milkweed is not limiting within their collective range. Moreover, there is no indication from these data that the summer population was ever truly diminished by changing agricultural practices in the Midwest that reduced milkweed in crop fields within that region. It is possible that the larger population is not as dependent on Midwestern agricultural milkweed as once thought, and/or that monarchs are adapting to increasingly human-altered landscapes. These results are timely and should bear on the upcoming USFWS decision on whether the monarch requires federal protection in the United States. Importantly, they argue that despite losses of many insects globally, the eastern North American monarch population is not in the same situation.
CONCEPT PAPER | doi:10.20944/preprints202007.0454.v1
Subject: Life Sciences, Genetics Keywords: gene evolution; gene formation; long non-coding RNA genes; pseudogenes; USP18; GGT5
Online: 20 July 2020 (04:39:41 CEST)
A small phylogenetically conserved sequence of 11,231 bp termed FAM247 is repeated in human chromosome 22 by segmental duplications. This sequence forms part of diverse genes that span evolutionary time, the protein genes being the earliest as they are present in zebrafish and/or mice genomes, the long non-coding RNA genes and pseudogenes the most recent as they appear to be present only in the human genome. We propose that the conserved sequence provides a nucleation site for new gene development at evolutionary conserved chromosomal loci where the FAM247 sequences reside. The FAM247 sequence also carries information in its open reading frames that provides protein exon amino acid sequences; one exon plays an integral role in immune system regulation, specifically, the function of ubiquitin specific protease (USP18) in the regulation of interferon. An analysis of this multifaceted sequence and the genesis of genes that contain it are presented.
ARTICLE | doi:10.20944/preprints202002.0038.v1
Subject: Life Sciences, Molecular Biology Keywords: allele specific expression; 6-BA; DNA methylation; long noncoding RNA; siRNA; poplar
Online: 4 February 2020 (05:22:28 CET)
The cytokinins play important roles in plant growth and development by regulating gene expression at genome wide level. DNA methylation is responsive to the external environment, but whether DNA methylation changes in response to cytokinin treatment to regulate gene expression is still unclear. Here, we used bisulfite sequencing and RNA sequencing to examine genome-wide DNA methylation and gene expression patterns in poplar (Populus tomentosa) after treatment with the synthetic cytokinin 6-benzylaminopurine (6-BA). We identified 566 significantly differentially methylated regions (DMRs) in response to 6-BA treatment. Transcriptome analysis showed that 501 protein-coding genes, 262 long non-coding RNAs, and 15,793 24-nt small interfering RNAs were differentially expressed under 6-BA treatment. Among these, 79% were differentially expressed between alleles in P. tomentosa. Combined DNA methylation and gene expression analysis demonstrated that DNA methylation plays an important role in regulating allele-specific gene expression. To further investigate the relationship between these 6-BA-responsive genes and phenotypic variation, we performed SNP analysis of 507 6-BA-responsive DMRs via re-sequencing using a natural population of P. tomentosa and identified 206 SNPs that were significantly associated with growth and wood properties. Association analysis indicated that 53% of loci with allele-specific expression had primarily dominant effects on poplar traits. Our comprehensive analyses of P. tomentosa DNA methylation and the regulation of allele-specific gene expression suggest that DNA methylation is an important regulator of imbalanced expression between allelic loci.
Subject: Earth Sciences, Geoinformatics Keywords: precipitation downscaling; convolutional neural networks; long short term memory networks; hydrological simulation
Online: 2 April 2019 (12:37:11 CEST)
Precipitation downscaling is widely employed for enhancing the resolution and accuracy of precipitation products from general circulation models (GCMs). In this study, we propose a novel statistical downscaling method to foster GCMs’ precipitation prediction resolution and accuracy for monsoon region. We develop a deep neural network composed of convolution and Long Short Term Memory (LSTM) recurrent module to estimate precipitation based on well-resolved atmospheric dynamical fields. The proposed model is compared against GCM precipitation product and classical downscaling methods in the Xiangjiang River Basin in South China. Results show considerable improvement compared to the ECMWF-Interim reanalysis precipitation. Also, the model outperforms benchmark downscaling approaches, including 1) quantile mapping, 2) support vector machine, and 3) convolutional neural network. To test the robustness of the model and its applicability in practical forecast, we apply the trained network for precipitation prediction forced by retrospective forecasts from ECMWF model. Compared to ECMWF precipitation forecast, our model makes better use of the resolved dynamical field for more accurate precipitation prediction at lead time from 1 day up to 2 weeks. This superiority decreases along forecast lead time, as GCM’s skill in predicting atmospheric dynamics being diminished by the chaotic effect. At last, we build a distributed hydrological model and force it with different sources of precipitation inputs. Hydrological simulation forced with the neural network precipitation estimation shows significant advantage over simulation forced with the original ERA-Interim precipitation (with NSE value increases from 0.06 to 0.64), and the performance is just slightly worse than the observed precipitation forced simulation (NSE=0.82). This further proves the value of the proposed downscaling method, and suggests its potential for hydrological forecasts.
ARTICLE | doi:10.20944/preprints201812.0049.v1
Subject: Physical Sciences, Particle & Field Physics Keywords: NA61/SHINE, upgrade, open charm, silicon detector, TPC, CERN long shutdown 2
Online: 4 December 2018 (09:24:42 CET)
The NA61/SHINE experiment studies hadron production in hadron-hadron, hadron-nucleus and nucleus-nucleus collisions. The physics programme includes the study of the onset of deconfinement and search for the critical point as well as reference measurements for neutrino and cosmic ray experiments. For strong interactions, future plans are to extend the programme of study of the onset of deconfinement by measurements of open-charm and possibly other short-lived, exotic particle production in nucleus-nucleus collisions. This new programme is planned to start after 2020 and requires upgrades to the present NA61/SHINE detector setup. Besides the construction of a large acceptance silicon detector, a 10-fold increase of the event recording rate is foreseen, which will necessitate a general upgrade of most detectors.
ARTICLE | doi:10.20944/preprints201811.0126.v1
Subject: Engineering, Electrical & Electronic Engineering Keywords: Speech/Music Classification; Enhanced Voice Service, Long Short-Term Memory, Big Data
Online: 5 November 2018 (17:02:36 CET)
Speech/music classification that facilitates optimized signal processing from classification results has been extensively adapted as an essential part of various electronics applications, such as multi-rate audio codecs, automatic speech recognition, and multimedia document indexing. In this paper, a new technique to improve the robustness of speech/music classifier for 3GPP enhanced voice service (EVS) using long short-term memory (LSTM) is proposed. For effective speech/music classification, feature vectors implemented with the LSTM are chosen from the features of the EVS. Experiments show that LSTM-based speech/music classification produces better results than conventional EVS under a variety of conditions and types of speech/music data.
ARTICLE | doi:10.20944/preprints201809.0169.v1
Subject: Biology, Animal Sciences & Zoology Keywords: European sardine; draft genome; teleosts; comparative genomics; long chain polyunsaturated fatty acids
Online: 10 September 2018 (12:37:23 CEST)
Clupeiformes, such as sardines and herrings, represent an important share of worldwide fisheries. Among those, the European sardine (Sardina pilchardus, Walbaum 1792) exhibits significant commercial relevance. While the last decade showed a steady and sharp decline in capture levels, recent advances in culture husbandry represent promising research avenues. Yet, the complete absence of genomic resources from sardine imposes a severe bottleneck to understand its physiological and ecological requirements. We generated 69 Gbp of paired-end reads using Illumina HiSeq X Ten and assembled a draft genome assembly with an N50 scaffold length of 25579 bp and BUSCO completeness of 82.1% (Actinopterygii). The estimated size of the genome ranges between 655 and 850 Mb. Additionally, we generated a relatively high-level liver transcriptome. To deliver a proof of principle of the value of this dataset, we established the presence and function of enzymes (elovl2, elovl5 and fads2) that have pivotal roles in the biosynthesis of long chain polyunsaturated fatty acids, essential nutrients particularly abundant in oily fish such as sardines. Our study provides the first omics dataset from a valuable economic marine teleost species, the European sardine, an essential resource for their effective conservation, management and sustainable exploitation.
ARTICLE | doi:10.20944/preprints201808.0075.v2
Subject: Biology, Physiology Keywords: Long Term Evolution, LTE; 4G; mobile phone; nociception; pain; thermal pain threshold
Online: 20 August 2018 (15:01:09 CEST)
Although the majority of mobile phone (MP) users do not attribute adverse effects on health or well-being to MP-emitted radiofrequency (RF) electromagnetic fields (EMFs), the exponential increase in the number of RF devices necessitates continuing research aimed at the objective investigation of such concerns. In this work, we investigate the effects of acute exposure from Long Term Evolution (LTE) MP EMFs on thermal pain threshold in healthy young adults. We use a protocol that was validated in a previous study in a capsaicin-induced hyperalgesia model, and was also successfully used to show that exposure from an RF source mimicking a Universal Mobile Telecommunications System (UMTS) MP led to mildly stronger desensitization to repeated noxious thermal stimulation relative to the sham condition. Using the same experimental design, we did not find any effects of LTE exposure on thermal pain threshold. The present results are in accordance with previous evidence suggesting that effects are likely to be placebo/nocebo effects and are unrelated to the brief acute LTE EMF exposure itself. The fact that this is dissimilar to our previous results on UMTS exposure implies that RF modulations might differentially affect pain perception, and points to the necessity of further research in the topic.
ARTICLE | doi:10.20944/preprints201804.0248.v1
Subject: Medicine & Pharmacology, Ophthalmology Keywords: Ab interno trabeculectomy; Trabectome surgery; long-term outcomes; microinvasive glaucoma surgeries; MIGS
Online: 19 April 2018 (09:41:02 CEST)
Purpose: To analyze the five-year results of Trabectome ab interno trabeculectomy of a single glaucoma center. Method: In this retrospective interventional single-center case series, data of 93 patients undergoing ab interno trabeculotomy between September 2010, and December 2012 were included. Kaplan-Meier analysis was performed using success criteria defined as postoperative intraocular pressure (IOP) ≤21 mm Hg, or >20% reduction from preoperative IOP, and no need for further glaucoma surgery. Risk factors for failure were identified using Cox proportional hazards ratio (HR). Results: The retention rate for five years follow-up was 66%. The cumulative probability of success at 1, 2, 3, 4 and 5 years was 82.6%, 76.7%, 73.9%, 72.3%, and 67.5%. Risk factors for failure were lower baseline IOP (HR=0.27, P=0.001), younger age (HR=0.25, P=0.02), and higher central corneal thickness (HR=0.18, P= 0.01). Pseudoexfoliation was associated with a higher success rate (HR= 0.39, P=0.02). IOP was decreased significantly from 20.0±5.6 mmHg at baseline to 15.6±4.6 mmHg at 5-year follow-up (P=0.001). The baseline number of glaucoma medications was 1.8±1.2, which decreased to 1.0±1.2 medications at 5 years. Conclusion: Trabectome surgery was associated with a good long-term efficacy and safety profile in this single-center case series with a high retention rate. A higher baseline IOP, older age, thinner cornea, and pseudoexfoliation glaucoma were associated with a higher success rate.
ARTICLE | doi:10.20944/preprints202203.0140.v1
Subject: Mathematics & Computer Science, Artificial Intelligence & Robotics Keywords: Left ventricular ejection fraction; Left ventricle segmentation; Convolutional long short-term memory; Echocardiography
Online: 10 March 2022 (04:19:30 CET)
Cardiovascular disease is the leading cause of death worldwide. A key factor in assessing the risk of cardiovascular disease is left ventricular functional evaluation. Left ventricular (LV) systolic function is evaluated by measuring the left ventricular ejection fraction (LVEF) using echocardiography data. Therefore, quick and accurate left ventricle segmentation is important for estimating the LVEF. However, it is difficult to accurately segment the left ventricle due to changes in the shape and area of the left ventricle during cardiac cycles. In this study, we proposed a framework that considers changes in the shape and area of the left ventricle during the cardiac cycle by applying the convolutional long short-term memory (CLSTM) approach. In addition, we evaluated the left ventricular segmentation and multidimensional quantification of the proposed system in comparison to manual and automated segmentation methods. In addition, to assess the validity of CLSTM, the values of multi-dimensional quantification metrics were compared and analyzed using graphs and Bland–Altman plots on a frame-by-frame basis. We demonstrated that the CLSTM method effectively segments the left ventricle by considering the LV activity. In conclusion, we demonstrated that LV segmentation based on our framework may be utilized to accurately estimate LVEF values.
ARTICLE | doi:10.20944/preprints202203.0099.v1
Subject: Medicine & Pharmacology, Psychiatry & Mental Health Studies Keywords: long-acting injectable; antipsychotic; depot; schizophrenia spectrum disorder; schizophrenia; schizoaffective; inpatient; prescribing pattern
Online: 7 March 2022 (12:33:39 CET)
Long-acting injectable antipsychotics (LAIs) offer many benefits to patients with schizophrenia spectrum disorder (SSD). They are used with very different frequencies due to questions of eligibility or patients’ and prescribers’ attitudes towards LAI use. We assessed the prescribing rates of LAIs in a large academic psychiatric hospital with public service mandate in Switzerland and compared them with other countries and health care systems. To our knowledge this study is the first to investigate the inpatient LAI-use in Europe. Medical records of all patients diagnosed with SSD discharged from the Clinic of Adult Psychiatry of the University Hospital of Psychiatry Zurich over a 12-month period from January to December 2019 were evaluated regarding the prescribed antipsychotics at the time of discharge. The rates of use of LAIs among all patients and among patients receiving LAI eligible antipsychotic substances were assessed retrospectively. We assessed records of 885 patients with SSD. Among all cases 13.9% received an LAI. Among patients who received antipsychotic medication that was eligible for LAI use 28.3% (n=434) received an agent as LAI. These included paliperidone palmitate (69.9%), aripiprazole monohydrate (14.6%), risperidone (4.9%) and first-generation LAIs (9.8%). Compared to international frequencies of LAI administration, the prescription rate of LAIs in SSD patients was low. Further studies will evaluate patient- and prescriber-related reasons for this low rate.
ARTICLE | doi:10.20944/preprints202110.0182.v1
Subject: Engineering, Energy & Fuel Technology Keywords: Electricity peak load; Taoussa’s energy sources; Long-term electricity demand planning; Scenarios simulation
Online: 12 October 2021 (12:53:37 CEST)
A long-term forecast study on the electricity demand of Taoussa of Mali is conducted in this paper, with various scenarios of socioeconomic and technological conditions. The analysis tool, which is applied in scenarios simulation, is the Model for Analysis of Energy Demand from the International Atomic Energy Agency. The analysis results are annual electricity demand and peak load forecast for the electrification from the period 2020 to 2035. During the planning period, the analysis results show that the electricity demand will increase to 49.40 MW (332.57 GWh) for the low scenario (LS), 66.46 MW (472.61 GWh) for the reference scenario (RS), and 89.47 MW (635 GWh) for the high scenario (HS). In addition, the total electricity demand increased at an average rate of 8.13% in the LS, 10.31% in the RS and 12.56% in the HS in all sectors. The electricity peak demand is expected to grow at 7.92%, 10.53% and 12.91% corresponding to the three scenarios; in this case, the system peak demand in 2035 will increase to 64.88 MW for the LS, 92.2 MW for the RS and 126.22 MW, the days of peak load are between 17th -23rd in May. The Industry sector will be the biggest electricity consumer of Taoussa area.
ARTICLE | doi:10.20944/preprints202110.0102.v1
Subject: Engineering, Automotive Engineering Keywords: long-haul truck; crash scenarios; GIDAS; CARE; crash causation; European national crash data
Online: 6 October 2021 (10:35:39 CEST)
This paper addresses crashes involving heavy goods vehicles (HGV) in Europe focusing on long-haul trucks weighing 16 tons or more (16t+). The identification of the most critical scenarios and their characteristics is based on a three-level analysis: general crash statistics from CARE addressing all HGVs, results about 16t+ trucks from national crash databases and a detailed study of in-depth crash data from GIDAS, including a crash causation analysis. Most European HGV crashes occur in clear weather, during daylight, on dry roads, outside city limits, and on non-highway roads. Three main scenarios for 16t+ trucks are characterized in-depth: (1) rear-end crashes in which the truck is the striking partner, (2) conflicts during right turn maneuvers of the truck and a cyclist riding alongside and (3) pedestrians crossing the road in front of the truck. Among truck-related crash causes, information admission failures (e.g. distraction) were the main causing factors in 72% of cases in scenario (1) while information access problems (e.g. blind spots) were present for 72% of cases in scenario (2) and 75% of cases in scenario (3). The results provide both a global overview and sufficient depth of analysis in the most relevant cases and thereby aid safety system development.
ARTICLE | doi:10.20944/preprints202109.0316.v1
Subject: Biology, Physiology Keywords: temporal lobe epilepsy; hippocampus; 4-aminopyridine; epilepsy model; long-term potentiation; AMPA receptor.
Online: 17 September 2021 (12:45:31 CEST)
Even brief epileptic seizures can lead to activity-dependent structural remodeling of neural circuitry. Animal models show that the functional plasticity of synapses and changes in the intrinsic excitability of neurons can be crucial for epileptogenesis. However, the exact mechanisms underlying epileptogenesis remain unclear. We induced epileptiform activity in rat hippocampal slices for 15 min using a 4-aminopyridine (4-AP) in vitro model and observed hippocampal hyperexcitability for at least 1 hour. We tested several possible mechanisms of this hyperexcitability, including changes in intrinsic membrane properties of neurons, presynaptic and postsynaptic alterations. Neither input resistance nor other essential biophysical properties of hippocampal CA1 pyramidal neurons were affected by epileptiform activity. The glutamate release probability also remained unchanged, as the frequency of miniature EPSCs and the paired amplitude ratio of evoked responses did not change after epileptiform activity. However, we found an increase in the AMPA/NMDA ratio, suggesting alterations in the properties of postsynaptic glutamatergic receptors. Thus, the increase in excitability of hippocampal neural networks is realized through postsynaptic mechanisms. In contrast, the intrinsic membrane properties of neurons and the probability of glutamate release from presynaptic terminals are not affected in a 4-AP model.
ARTICLE | doi:10.20944/preprints202106.0624.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: Esophageal squamous cell carcinoma; Metformin; Long noncoding RNAs; CCAT1; SPRY4-IT1; c-Myc
Online: 25 June 2021 (12:41:51 CEST)
Evidence indicates that the long noncoding RNAs are involved in the metformin-mediated anti-cancer processes. However, the potential effects of the long noncoding RNAs in metformin-mediated anti-tumor processes in esophageal squamous cell carcinomas (ESCC) are still elusive. This study uncovered that metformin decreases the level of long noncoding RNAs CCAT1 and SPRY4-IT1 thereby contributing to the down-regulation of c-Myc and vimentin. Also, the RNA level test of human ESCC tissue confirmed the positive correlation between CCAT1 and c-Myc. These findings demonstrated that metformin facilitated anti-cancer effects by targeting the 2 long noncoding RNAs (CCAT1 and SPRY4-IT1) and their consequential targets c-Myc and vimentin. Therefore, the CCAT1 and SPRY4-IT1 might act as novel molecular targets that mediate the anti-tumor effects in esophageal squamous cell carcinoma. This helps in predicting the treatment response of metformin in patients diagnosed with esophageal squamous cell carcinoma.
ARTICLE | doi:10.20944/preprints202104.0269.v1
Subject: Keywords: Travel Time Prediction; Deep Learning; Long Short Term Memory Networks; transit; temporal correlation
Online: 9 April 2021 (15:04:06 CEST)
This study introduces a comparative analysis of two deep learning (multilayer perceptron neural networks (MLP-NN) and the long short term memory networks (LSTMN)) models for transit travel time prediction. The two models were trained and tested using one-year worth of data for a bus route in Blacksburg, Virginia. In this study, the travel time was predicted between each two successive stations to all the model to be extended to include bus dwell times. Additionally, two additional models were developed for each category (MLP of LSTM): one for only segments including controlled intersections (controlled segments) and another for segments with no control devices along them (uncontrolled segments). The results show that the LSTM models outperform the MLP models with a RMSE of 17.69 sec compared to 18.81 sec. When splitting the data into controlled and uncontrolled segments, the RMSE values reduced to 17.33 sec for the controlled segments and 4.28 sec for the uncontrolled segments when applying the LSTM model. Whereas, the RMSE values were 19.39 sec for the controlled segments and 4.67 sec for the uncontrolled segments when applying the MLP model. These results demonstrate that the uncertainty in traffic conditions introduced by traffic control devices has a significant impact on travel time predictions. Nonetheless, the results demonstrate that the LSTMN is a promising tool that can has the ability to account for the temporal correlation within the data. The developed models are also promising tools for reasonable travel time predictions in transit applications.