COVID-19 Pandemic management has become the top priority of Government Institutions globally, which is justifiable seeing the high mortality of the disease. In India, Lockdowns by National, State and Local level administrations have greatly reduced the spread of the SARS COV-2 Virus. Some areas with a greater proportion of COVID-19 patients have been declared hotspots with increased restrictions on public activities through law enforcement. But quite often delay in identification of these hotspots leads to community transmission of the Virus thus aggravating the problem. A method to identify the areas which are at risk of becoming the next hotspot for the disease is the need of the hour[1]. In this Research document we will find the probable risk factors and make an appropriate scale to measure the vulnerability of an area, identified by its Postal code. To help with this a Pan India survey by the title of “Survey on General Indian population on the level of preparedness for COVID-19 pandemic” was launched and received around 1250 submissions, with the acquired data we will evaluate the risk factors and make appropriate scale to identify ‘pre-hotspots’.

Designed by a group of ME/CFS researchers and health professionals, the European Network on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (EUROMENE) has received funding from the European Cooperation is Science and Technology (COST) (https://www.cost.eu/cost-actions/what-are-cost-actions/ ) - COST action 15111 - from 2016 to 2020. The main goal of the Cost Action was to assess the existing fragmented knowledge and experience on health care delivery for people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in European countries, and to enhance coordinated research and health care provision in this field. We report on the recommendations for clinical diagnosis, heath services and care for people with ME/CFS in Europe, as prepared by the group of clinicians and researchers from 22 countries and 55 European health professionals and researchers, who have been informed by people with ME/CFS (https://www.cost.eu/actions/CA15111/#tabs|Name:overview).

Introduction: An epidemic of Coronavirus Disease 2019 (COVID-19) begun in December 2019 in China, causing a Public Health Emergency of International Concern. Among raised questions, clinical, laboratory, and imaging features have been partially characterized in some observational studies. No systematic reviews have been published on this matter. Methods: We performed a systematic literature review with meta-analysis, using three databases to assess clinical, laboratory, imaging features, and outcomes of COVID-19 confirmed cases. Observational studies, and also case reports, were included and analyzed separately. We performed a random-effects model meta-analysis to calculate the pooled prevalence and 95% confidence interval (95%CI). Results: 660 articles were retrieved (1/1/2020-2/23/2020). After screening by abstract/title, 27 articles were selected for full-text assessment. Of them, 19 were finally included for qualitative and quantitative analyses. Additionally, 39 case report articles were included and analyzed separately. For 656 patients, fever (88.7%, 95%CI 84.5-92.9%), cough (57.6%, 40.8-74.4%) and dyspnea (45.6%, 10.9-80.4%) were the most prevalent manifestations. Among the patients, 20.3% (95%CI 10.0-30.6%) required intensive care unit (ICU), with 32.8% presenting acute respiratory distress syndrome (ARDS) (95%CI 13.7-51.8), 6.2% (95%CI 3.1-9.3) with shock and 13.9% (95%CI 6.2-21.5%) of hospitalized patients with fatal outcomes (case fatality rate, CFR).Conclusion: COVID-19 brings a huge burden to healthcare facilities, especially in patients with comorbidities. ICU was required for approximately 20% of polymorbid, COVID-19 infected patients and this group was associated with a CFR of over 13%. As this virus spreads globally, countries need to urgently prepare human resources, infrastructure, and facilities to treat severe COVID-19.

COVID-19 is causing major turmoil around the globe, and the clinical trial industry is likely to face unprecedented challenges to health and business sectors. In an effort to find a suitable treatment and prevention options for COVID-19, several COVID-19 clinical trials are being planned and initiated, while a large number of clinical trials for non- COVID-19 indications are suffering delays. With over more than 1000 trials being disrupted and more trials being added to this category daily, there is a direct impact on trial site activation and patient enrolment. This analysis deals with the specific impacts of the COVID-19 pandemic on the clinical trial and pharmaceutical industry. The objective of this study is to provide an updated information of the disrupted clinical trials and its impact on various therapeutic areas and different drugs. Among the severely affected clinical trials, oncology and CNS trials are the hardest hit therapy areas.This article will certainly emphasize the need for advanced and innovative approaches to maintain the health of the clinical trial ecosystem by continuing the existing trials and the start of the new studies. We have to take and follow necessary actions to guarantee that the initiatives will not be locked during the COVID-19 pandemic, both for the treatment of patients and for the researchers to conduct decision-relevant clinical trials.

The prevalence of corona virus and the novel COVID-19 disease in the entire globe has exacerbated different impact on socioeconomic spectrum in the world, including water use pattern. Thus a research was conducted to examine the comparative use of water during pre- and post-COVID-19 lockdown pattern among post-primary schools in Iwo, Osun State, Nigeria. A survey was conducted among fifteen schools which were randomly selected, but with eight public and seven private schools for the investigation. Both descriptive and inferential statistical techniques were used in data analysis. The results revealed that the major source of water to the schools investigated is ground water which is obtained through hand-dug wells and boreholes. It was further discovered that there was increase in water use during post-COVID-19 lockdown era as a result of the directive by the government that clean water should be provided for hand-washing by all schools regardless of the owner to curtail the spread of COVID-19 disease in the country. One sample t-test also revealed that there was a significant difference in water use at (p<0.01) level. It is recommended that the government and other stakeholders in water sector to ensure that all-time and non-seasonal dependent source of water be provided rather than ground water source which is susceptible to variations in water yields from seasonal variations. This will enable continuous clean water supply, for all purposes, including COVID-19 protocols.

World is now experiencing a major health calamity due to the coronavirus disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV- 2). The foremost challenge facing the scientific community is to explore the growth and transmission capability of the virus. Use of artificial intelligence (AI), such as, deep learning, in (i) rapid disease detection from x-ray/computerized tomography (CT)/ high-resolution computed tomography (HRCT) images, (ii) accurate prediction of the epidemic patterns and their saturation throughout the globe, (iii) identification of the epicenter in each country/state and forecasting the disease from social networking data, (iv) prediction of drug-protein interactions for repurposing the drugs, and (v) socio-economic impact and prediction of future relapses, has attracted much attention. In the present manuscript, we describe the role of various AI-based technologies for rapid and efficient detection from CT images complementing quantitative real time polymerase chain reaction (qRT-PCR) and immunodiagnostic assays. AI-based technologies to anticipate the current pandemic pattern, possibility of future relapses and socio-economic impact are also discussed. We inspect how the virus transmits depending on different factors, such as, population density and mobility among others. We depict how AI-based mobile app for contact tracing and surveys can prevent the transmission. A modified deep learning technique can assess affinity of the most probable drugs to treat COVID-19. Here a few effective antiviral drugs, such as, Geneticin, Avermectin B1, and Ancriviroc among others, have been reported with their appropriate validation from previous investigations.

With the growing hope that disease-modifying treatments could target the molecular basis of neurodegenerative diseases even before the onset of symptoms, there is mounting pressure to define disease entities based on pathophysiology rather than on clinical syndromes. The Alzheimer’s disease research community has recently transitioned from diagnostic criteria based on an amnestic syndrome to a purely biomarker-based disease definition, relying on the demonstration of amyloid-beta pathology, tau pathology, and neurodegeneration. In contrast, current diagnostic criteria for Parkinson’s disease still rely on the presence of the well-described clinical syndrome of parkinsonism, with the addition of characteristic motor- and non-motor signs and symptoms. However, there is now unequivocal evidence that Parkinson’s disease starts years before the onset of parkinsonism. Furthermore, neuropathologically defined Lewy body disease is clinically heterogeneous, combining a range of motor, non-motor, dopaminergic and non-dopaminergic features. Finally, clinically defined Parkinson’s disease has diverse underlying etiologies most, but not all, associated with α-synuclein positive Lewy pathology. In light of recent scientific advances, we propose a biologically based definition for the diagnosis of Parkinson's disease, initially to be used for research purposes. The criteria use a three-component ‘G-S-N’ system. The first is documentation of defined gene variants (‘G’), which cause or strongly predispose to PD as the most upstream component. The second is α-synuclein pathology (‘S’), currently defined as pathological α-synuclein deposition in tissue or positive α-synuclein seeding assays. The third is evidence of underlying neurodegeneration (‘N’), currently defined by specific neuroimaging procedures. The associated clinical syndrome (‘C’) is defined by a single high-specificity feature or multiple lower-specificity features. Initiating this transition will enable the field to fuel both basic and clinical research and move closer to the precision medicine required to develop clinically meaningful disease-modifying therapies. We acknowledge current limitations, ethical implications, and the need for prospective validation of this approach.

Artificial intelligence (AI)-based models hold the potential to transform higher education if adopted properly and ethically. A prime example is ChatGPT with earlier studies indicating its widespread adoption in academia and by university students. The current study aimed to identify the factors influencing the attitude towards ChatGPT and its usage among university students in Arab countries. A previous survey instrument termed Technology Acceptance Model Edited to Assess ChatGPT Adoption (TAME-ChatGPT) was administered online using a convenience-based approach among the contacts of the authors. Confirmatory factor analysis (CFA) for the survey constructs was done using root mean square error of approximation (RMSEA), standardized root mean square residual (SRMR), comparative fit index (CFI), and Tucker-Lewis index (TLI). The final study sample comprised a total of 2240 participant divided as follows: Iraq (n=736, 32.9%), Kuwait (n=582, 26.0%), Egypt (n=417, 18.6%), Lebanon (n=263, 11.7%), and Jordan (n=242, 10.8%). A total of 1048 respondents heard of ChatGPT before the study (46.8%), of which 551 used ChatGPT (52.6%). The mean scores of TAME-ChatGPT constructs showed that the ease of ChatGPT use, positive attitude towards technology and social influence, higher perceived usefulness, the influence of behavioral/cognitive factors, low perceived risks and low anxiety were the determinants of positive attitude to ChatGPT and its use. For both the attitude and usage scales of TAME-ChatGPT, CFA collectively yielded satisfactory fit indices as indicated by low RMSEA and SRMR together with high CFI and TLI. Multivariate analysis showed that attitude to ChatGPT use was significantly influenced by country of residence, age, university type, and the latest grade point average of the students. The current study confirmed the validity of TAME-ChatGPT as a survey instrument to assess the possible determinants of ChatGPT use among university students in Arab countries. The study findings highlighted that successful adoption of ChatGPT in higher education could be dependent on perceived ease of use, usefulness, positive attitudes to technology, social influence, behavioral/cognitive factors, lower anxiety, and minimal perceived risks. The utility of ChatGPT in higher education requires policies that should be tailored for various settings, considering the differences observed in attitude towards ChatGPT among participating students in this study.

ChatGPT is gaining widespread acceptance for its ability to generate natural language sentences in response to various inputs and is expected to become a supplementary tool for diagnosing and determining treatment policies in clinical settings. ChatGPT was used to evaluate its ability to perform clinical inference and accuracy in answering questions on the 117th Japanese National Medical Licensing Examination held in February 2023. The exam questions were manually inputted into ChatGPT's window, and the accuracy of ChatGPT's responses was determined based on answers provided by a preparatory school. ChatGPT provided answers for 389 out of 400 questions, and its overall correct answer rate was 55.0%. The correct answer rate for 5-choice-1, 5-choice-2, and 5-choice-3 were 57.8%, 42.9%, and 41.2%, respectively. The highest correct answer rate was for the compulsory exam (67.0%), followed by the specific knowledge exam (54.1%) and the cross category exam (47.9%). The correct answer rate for non-image questions was 56.2% and for image questions, it was 51.5%. The study suggests that ChatGPT has potential to support healthcare professionals in clinical decision-making in Japanese clinical settings, but caution should be exercised in interpreting and using the answers generated by ChatGPT due to room for improvement in performance.

The use of machine learning (ML) approaches to target clinical problems is called to revolutionize clinical decision-making. The success of these tools is subjected to the understanding of the intrinsic processes being used during the classical pathway by which clinicians make decisions. In a parallelism with this pathway, ML can have an impact at four levels: for data acquisition, predominantly by extracting standardized, high-quality information with the smallest possible learning curve; for feature extraction, by discharging healthcare practitioners from performing tedious measurements on raw data; for interpretation, by digesting complex, heterogeneous data in order to augment the understanding of the patient status; and for decision support, by leveraging the previous step to predict clinical outcomes, response to treatment or to recommend a specific intervention. This paper discusses the state-of-the-art, as well as the current clinical status and challenges associated with each of these tasks, together with the challenges related to the learning process, the auditability/traceability, the system infrastructure and the integration within clinical processes.

With the COVID-19 pandemic now ongoing for close to a year, people all over the world are still waiting for a vaccine to become available. The initial focus of accelerated global research and development efforts to bring a vaccine to market as soon as possible was on novel platform technologies that promised speed but had limited history in the clinic. In contrast, recombinant protein vaccines, with numerous examples in the clinic for many years, missed out on the early wave of investments from government and industry. Emerging data are now surfacing suggesting that recombinant protein vaccines indeed might offer an advantage or complement to the nucleic acid or viral vector vaccines that will likely reach the clinic faster. Here, we summarize the current public information on the nature and on the development status of recombinant subunit antigens and adjuvants targeting SARS-CoV-2 infections.

Coronavirus Disease 2019 (COVID-19), caused by a novel coronavirus named Severe Acute Respiratory Syndrome - Coronavirus-2 (SARS-CoV-2), emerged in early December 2019 in China and attained a pandemic situation worldwide by its rapid spread to nearly 167 countries with 287.239 confirmed cases and 11.921 human deaths with a case fatality rate (CFR) of around 4 per cent. Bats were considered as the reservoir host, and the search of a probable intermediate host is still going on. Animals have anticipated culprit of SARS-CoV-2 as of now. The disease is mainly manifested by pneumonia and related respiratory signs and symptoms, but the involvement of the gastrointestinal system and nervous system is also suggested. The severe form of the disease associated with death is mainly reported in older and immune-compromised patients with pre-existing disease history. Death in severe cases is attributed to respiratory failure associated with hyperinflammation. Cytokine storm syndrome associated with rampant inflammation in response to SARS-CoV-2 infection is considered as the leading killer of COVID-19 patients. COVID-19 patients were reported with higher levels of many pro-inflammatory cytokines and chemokines like IFN-g, IL-1b, IP-10, and MCP-1. Furthermore, severe cases of COVID-19 revealed higher levels of TNF-α, G-CSF, and MIP-1A. Blood profile of the COVID-19 patients exhibits lymphopenia, leucopenia, thrombocytopenia and RNAaemia along with increased levels of aspartate aminotransferase. SARS-CoV-2 infection in pregnant women does not lead to fetus mortalities unlike other zoonotic coronaviruses like SARS-CoV and MERS-CoV, with no evidence of intrauterine transmission to neonates. Rapid and confirmatory diagnostics have been developed, and high efforts are being made to develop effective vaccines and therapeutics. In the absence of any virus-specific therapeutic, internationally health care authorities are recommending adoption of effective prevention and control measures to counter and contain this pandemic virus. This paper is an overview of this virus and the disease with a particular focus on SARS-COV-2 / COVID-19 clinical pathology, pathogenesis and immunopathology along with a few recent research developments.

Objective: To examine the burnout syndrome among the healthcare personnel in Puerto Rico during the COVID-19 pandemic. Methods: Descriptive study that pursues to understand burnout syndrome in the clinical personnel in Puerto Rico. The Maslach Burnout Inventory (MBI) was sent via email to healthcare professionals around the island. Furthermore, open questions were asked to the participants. Results: The overall burnout level on the clinical personnel was found to be moderate. Nonetheless, in physicians, 12.1% had severe burnout levels compared to a 13.1% score in nurses. Additionally, 92.4% of physicians and 100% of nurses had moderate to severe burnout. In the three subscales, nurses scored high levels in all of them, and physicians were high in Emotional Exhaustion and moderate level in Depersonalization and Personal Accomplishment at Work. There were high levels of burnout syndrome of the clinical personnel in Puerto Rico. Conclusion: Since the beginning of the COVID-19 pandemic, over 90% of healthcare professionals in Puerto Rico have been working with moderate to severe burnout syndrome, being the nurses the most affected. Key Words: Burnout syndrome, MBI, Clinical personnel, COVID-19, SARS-CoV-2

MicroRNAs (miRNAs) are crucial regulatory RNAs, originated from hairpin precursors. For the past decade, researchers are focusing extensively on miRNA profiles in various plants. However studies on precursor miRNAs (pre-miRNAs) global profiling stay static even in model plants. Here, for the first time in a non-model plant, Abelmoschus esculentus with negligible genome information, we are reporting the global profiling to characterize the miRNAs and their associated pre-miRNAs by applying next generation sequencing approach. Preliminarily we performed sRNA (small RNA) sequencing with five biological replicates of leaf samples to attain 207,285,863 reads and data analysis using miRPlant keyed out 128 known and 845 novel miRNA candidates. With the objective to seize their associated hairpin precursors, we accomplished pre-miRNA sequencing to attain 83,269,844 reads. The paired end reads are merged, adaptor trimmed and the resulting 40-241 nt (nucleotide) sequences were picked out for analysis by using perl scripts from miRGrep tool and in-house built shell script for Minimum Fold Energy Index (MFEI) calculation. Applying stringent criteria of dicer cleavage pattern and perfect stem loop structure revealed precursors for 57 known miRNAs of 15 families and 18 novel miRNAs. Quantitative Real Time (qRT) PCR was performed to determine the expression of selected miRNAs.

The COVID-19 pandemic is a devastating blow to the entire world community and changes the order of human life. All efforts and strategies are being carried out to contain and reduce the spread of the SARS-COV-2 virus, both by tightening the health protocol and using vaccines to the public. Currently, several vaccines are available and have passed phase 3 clinical trials, such as vector vaccines (Gamaleya Sputnik V Russia, University of Oxford/AstraZeneca, CanSino, and Janssen Pharmaceutical Companies), mRNA-based vaccines (Moderna/BioNTech/Fosun Pharma/Pfizer), inactivated vaccines (SinoVac and SinoPharm from China, Covaxin from Bharat Biotech India), and adjuvanted recombinant protein nanoparticles (Novavax from the USA) are expected to be able to suppress the spread of the virus and produce a minimum of 70 percent herd-immunity in a population. Each vaccine's efficacy varies from the lowest, namely the Sinovac vaccine (CoronaVac) 50% to the highest the Novavax vaccine (NVX-Cov2373) 96% effectivity value. Moreover, further rigorous research is still being carried out for the development of an effective and efficient vaccine.

The Coronavirus disease due to SARS-CoV-2 emerged in Wuhan city, China in December 2019 and rapidly spread more than 200 countries as a global health pandemic. There are more 3 million confirmed cases and around 207,000 fatalities. The primary manifestation is respiratory and cardiac but neurological manifestations are being reported in the literature as case reports and case series. The most common reported symptoms to include headache and dizziness followed by encephalopathy and delirium. Among the complications noted are Cerebrovascular accident, Guillian barre syndrome, acute transverse myelitis, and acute encephalitis. The most common peripheral manifestation was hyposmia. It is further noted that sometimes the neurological manifestations can precede the typical features like fever and cough and later on typical manifestations develop in these patients. Hence a high index of suspicion is required for timely diagnosis and isolation of cases to prevent the spread in neurology wards. We present a narrative review of the neurological manifestations and complications of COVID-19. Our aim is to update the neurologists and physicians working with suspected cases of COVID-19 about the possible neurological presentations and the probable neurological complications resulting from this novel virus infection.

This study investigates the effect of perceived discrimination on the mental health of Afghan refugees, and secondly, tests the distress moderating effects of pre-migration traumatic experiences and post-resettlement adjustment factors. In a cross-sectional design, 259 Afghans completed surveys assessing perceived discrimination and a number of other factors using scales developed through inductive techniques. Multivariate analyses consisted of a series of hierarchical regressions testing the effect of perceived discrimination on distress, followed by a sequential analysis of moderator variables. Perceived discrimination was significantly associated with higher distress, and this relationship was stronger among those with a strong intra-ethnic identity, high civic engagement, and high pre-resettlement traumatic experiences. Discrimination is a significant source of stress for Afghan refugees, which may exacerbate stresses associated with other post-migration stressors. Future research is needed to tailor interventions that can help mitigate the stress associated with discrimination among this highly vulnerable group.

Noni juice is a globally popular health beverage that originates from the tropics. Traditional Tahitian healers believe the noni plant to be useful for a wide range of maladies, and noni juice consumers throughout the world have similar perceptions. Nevertheless, human clinical trials are necessary for an understanding of what the health benefits of noni juice truly are. A review of published human intervention studies suggest that noni juice may provide protection against tobacco smoke-induced DNA damage, blood lipid and homocysteine elevation, and systemic inflammation. Human interventions studies also suggest that noni juice may improve joint health, increase physical endurance, increase immune activity, inhibit glycation of proteins, aid weight management, help maintain bone health in women, help maintain normal blood pressure, and improve gum health. Further, these studies point to noni juice possessing notable antioxidant activity, more so than the other fruit juices that served as placebos. It is this antioxidant effect, and its interaction with the immune system and inflammation pathways, that may account for many of the observed health benefits of noni juice. However, the existing evidence does have some limitations in its application to noni juice products in general as all the peer-reviewed human interventions studies to-date have involved only one source of French Polynesian noni juice. Geographical factors and variations in processing methods are known to produce commercial noni juice products with divergent phytochemical and nutrient compositions. Therefore, other sources of noni products may have different toxicological and pharmacological profiles.

Background: One way to demonstrate the existence of nursing is to develop a nursing theory model through nursing research which can ultimately be implemented in nursing practice. RAM is one of the most frequently used models in guiding nursing research. Roy's Adaptation Model (RAM) is one of the most useful conceptual frameworks that guide nursing practice, direct research, and influence education. Theory-guided nursing practice is fundamental in providing the framework for developing superior and quality nursing care.Objectives: This systematic review aims to critically analyze recent studies using RAM as a conceptual framework to identify the effectiveness of this model in guiding nursing research.Methods: A literature search was conducted on five databases, namely SCOPUS, PubMed, ProQuest, ScienceDirect, and SAGEPub. There were no population boundaries and diagnoses involved in the study. The study is a quantitative design focused on publication between 2015-2021. The methodological quality of applying the Cochrane and JBI bias tools. The analysis uses narrative synthesis.Results: 20 studies were found out of 1,315 studies. The research population found is very diverse. The given intervention follows the conceptual framework of RAM. RAM-based interventions effectively overcome the problems experienced by patients and reduce the perceived symptoms and improve the patient's quality of life.Conclusion: The conceptual use of RAM theory in nursing research has been widely reported. RAM-based interventions have a significant impact and have strong evidence-based practice in improving patient health status.

The purpose of current study was to investigate the expression characteristic of circular RNAs (circRNAs) in peripheral blood of type 2 diabetes mellitus (T2DM) patients and their potentials as diagnostic biomarkers for pre-diabetes and T2DM. In present study, the circRNAs in the peripheral blood from 6 healthy individuals and 6 T2DM patients were collected for microarray analysis. The results indicated that there were 489 differentially expressed circRNAs, of which 78 were upregulated and 411 were downregulated in the T2DM group. Then we selected 5 circRNAs as the candidate biomarkers under a stricter screening criteria and further verified them in another cohort (control group, n=20; pre-diabetes group, n =20; T2DM group; n=20). 3 of the 5 circRNAs presented upregulated expression in the experimental groups, including 2 circRNAs of the T2DM group that had higher expression than the pre-diabetes group. Hsa_circ_0054633 was identified to have the largest area value under the carve (AUC). In another independent cohort (control group, n=60; pre-diabetes group, n=63; T2DM group, n=64), the diagnostic capacity of hsa_circ_0054633 was tested. The results showed that the AUC for the diagnosis of pre-diabetes was 0.751(95% confidence interval=[0. 666-0.835], P＜0.001) while it was 0.793 ([0.716-0.871], P＜0.001) for the diagnosis of T2DM. After including the risk factors of T2DM, the AUC increased to 0.841 ([0.773-0.910], P <0.001) and 0.834 ([0.762-0.905], P <0.001), respectively. Hsa_circ_0054633 presented a certain diagnostic capability for pre-diabetes and T2DM.

There is a current worldwide outbreak of a new type of coronavirus (2019-nCoV), which originated from China and has now spread to 17 other countries. Governments are under increase pressure to stop the outbreak spiraling into a global health emergency. At this stage, preparedness, transparency and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak sites, and from laboratories supporting the investigation. This paper aggregates and consolidates the virology, epidemiology, clinical management strategies from both English and Chinese literature, official news channels and other official government documents. In addition, by fitting the number of infections with a single-term exponential model, we report that the infection is spreading at an exponential rate, with a doubling period of 1.8 days.

The SARS-CoV-2 virus that causes the COVID-19 disease has wreaked havoc on the world community in terms of every imaginable parameter. The research output on COVID-19 has been nothing short of phenomenal, especially in the medical and biomedical sciences, where the search for a potential vaccine is being conducted in earnest. Much of the advanced research has been distributed in the leading medical journals, including the Journal of the American Medical Association (JAMA), where the latest research is distributed on a daily basis. The purpose of this paper is to provide some perspectives on 44 interesting and highly topical research papers that have been published in JAMA, at the time of writing, within the past two weeks. The diverse topics include public health, general medicine, internal medicine, oncology, paediatrics, geriatrics, and biostatistics.

Abstract. The COVID-19 has turned in to a global human tragedy and economic devastation. Governments have implemented lockdown measures, blocked international travel, and enforced other public containment measures to mitigate the virus morbidity and mortality. As of today, no drug has the power to fight the infection and bring normalcy to the utter chaos. This leaves us with only one choice namely an effective and safe vaccine that shall be manufactured as soon as possible and available to all countries and populations affected by the pandemic at an affordable price. There has been an unprecedented fast track path taken in R&D by the World community for developing an effective and safe vaccine. Platform technology has been exploited to develop candidate vaccines in a matter of days to weeks and as of now, 108 such vaccines are available. Six of these vaccines have entered clinical trials. As clinical trials are ‘rate-limiting’ and ‘time-consuming’, many innovative methods are in practice for a fast track. These include parallel phase I-II trials and obtaining efficacy data from phase IIb trials. Human ‘challenge experiments’ to confirm efficacy in humans is under serious consideration. The availability of the COVID-19 vaccine has become a race against time in the middle of death and devastation. There is an atmosphere of tremendous hype around the COVID-19 vaccine and developers are using every moment to make claims, which remain unverified. However, concerns are raised about a rush to deploy a COVID-19 vaccine. Applying ‘Quick fix’ and ‘short cuts’ can lead to errors with disastrous consequences.

Electronic health records (EHRs) are becoming a vital source of data for healthcare quality improvement, research, and operations. However, much of the most valuable information contained in EHRs remains buried in unstructured text. The field of clinical text mining has advanced rapidly in recent years, transitioning from rule-based approaches to machine learning and, more recently, deep learning. With new methods come new challenges, however, especially for those new to the field. This review provides an overview of clinical text mining for those who are encountering it for the first time (e.g. physician researchers, operational analytics teams, machine learning scientists from other domains). While not a comprehensive survey, it describes the state of the art, with a particular focus on new tasks and methods developed over the past few years. It also identifies key barriers between these remarkable technical advances and the practical realities of implementation at health systems and in industry.

The treatment of peptides has played an important role in clinical practice since the discovery of insulin therapy in the 1920s. Over 60 peptide drugs are approved in the United States (US and other regional mar-kets, and peptides continue to undergo drug discovery steadily. Peptide research and development has lev-eraged a wider range of structures known from other plant sources, via pharmacology and medicinal molecular biology, beyond its conventional focus on individual endogenous peptides. We build a comprehensive database of peptides that have met scientific studies with more than 150 constantly evolving peptides. Here we provide a simple overview of the peptide-based drug therapy environment, comprising evolutionary points of view, structural properties, operational thresholds, and explanation of the therapeutic area.

The technology-driven world of the 21^st century is currently confronted with a major threat to humankind in the form of the coronavirus disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). As of April 22, 2020, COVID-19 has claimed 169, 006 human lives and had spread to over 200 countries with more than 2,471,136 confirmed cases. The perpetually increasing figures associated with COVID-19 are disrupting the social and economic systems globally. The losses are unmatched and significantly higher compared to those from previously encountered pathogenic infections. Previously, two CoVs (SARS-CoV and Middle East respiratory syndrome-CoV) affected the human population in 2002 and 2012 in China and Saudi Arabia, respectively. Based on genomic similarities, animal-origin CoVs, primarily those infecting bats, civet cats, and pangolins, were presumed to be the source of emerging human CoVs, including the SARS-CoV-2. The cohesive approach amongst virologists, bioinformaticians, big data analysts, epidemiologists, and public health researchers across the globe has delivered high-end viral diagnostics. Similarly, vaccines and therapeutics against COVID-19 are currently in the pipeline for clinical trials. The rapidly evolving and popular technology of artificial intelligence played a major role in confirming and countering the COVID-19 pandemic using digital technologies and mathematical algorithms. In this review, we discuss the noteworthy advancements in the mitigation of the COVID-19 pandemic, focusing on the etiological viral agent, comparative genomic analysis, population susceptibility, disease epidemiology, animal reservoirs, laboratory animal models, disease transmission, diagnosis using artificial intelligence interventions, therapeutics and vaccines, and disease mitigation measures to combat disease dissemination.

Since the beginning of the year 2020, the global healthcare system has been challenged by the threat of the SARS-COV 2 virus. Molecular, antigen, and antibody testing are the mainstay to identify infected patients and fight the virus. Molecular and antigen tests that detect the presence of the virus are relevant in the acute phase only. Serological assays detect antibodies to the Sars-CoV-2 virus in the recovering and recovered phase. Each testing methodology has its advantages and disadvantages. To evaluate the test methods, sensitivity (percent positive agreement - PPA) and specificity (percent negative agreement – PNA) are the most common metrics utilized, followed by the positive and negative predictive value (PPV and NPV), the probability that a positive or negative test result represents a true positive or negative patient. In this paper, we illustrate how patient risk and clinical costs are driven by false-positive and false-negative results. We demonstrate the value of reporting PFP (probability of false positive results), PFN (probability of false negative results), and costs to patients and healthcare. These risk metrics can be calculated from the risk drivers of PPA and PNA combined with estimates of prevalence, cost, and Reff number (people infected by one positive SARS COV-2).

Objectives: Data sharing has become a requirement of many funding bodies and is becoming a scientific standard in many disciplines. In medical research, however, data sharing can conflict with clinicians’ obligation to protect patients’ privacy. General recommendations on data sharing exist also for clinical research, but so far lack practical and Swiss-specific aspects. The objective of this document is to provide practical recommendations for all relevant aspects of data sharing in agreement with legislation in Switzerland. Methods: This document was written by members of the Swiss CTU Network, a network of academic clinical trial units. The process did not follow a formalized Delphi process. After an internal consensus round, this report is now published as pre-print for external review. A second version will incorporate external comments. We plan to publish this document as a text in progress, as we expect relevant changes in related fields such as the development of further dedicated medical repositories or methodological advances in anonymization techniques. Results: We developed principles and practical recommendations with respect to informed consent, data management plan, anonymization, data structure and format, coding of variables, metadata and documentation, version control, selection of repository, requesting and use of data. We also provide a summary of legal aspects relevant for the Swiss context. Conclusions: The intension to share data has an impact not only after a clinical trial or an observational study is completed, but also during the planning period, the conduct and the analysis phase. Clinical researchers need to be aware at the beginning of a study on how to inform patients and at least the amount of work related to preparing data for sharing, metadata, and any further documentation. This report provides details of aspects to be considered, suggests decision criteria, and provides examples and checklists, in order to support data sharing in practice.

Background: Good clinical practice (GCP) training is the industry standard for ensuring the quality conduct of registrational clinical trials. However, concerns have been raised about whether the current structure and delivery of GCP training sufficiently prepares clinical investigators and their delegates to conduct clinical trials. Methods: We conducted qualitative semi-structured interviews with 13 clinical investigators and 10 research sponsors to 1) examine characteristics of the quality conduct of sponsored clinical trials, including critical tasks and concerns perceived as essential for trial quality, 2) identify key knowledge and skills required to perform critical tasks, and 3) identify gaps and redundancies in GCP training and areas of improvement to ensure the quality conduct of clinical trials. We used applied thematic analysis to analyze the data. Results: The top three tasks identified as critical for the quality conduct of clinical trials were obtaining informed consent, ensuring protocol compliance, and protecting participants’ health and safety. Respondents acknowledged that GCP principles address each of these critical tasks; however, they described many challenges and burdens of GCP training, including high training frequency and repetitive content. Respondents suggested moving beyond GCP training as a mere check-box activity by making it more effective, engaging, and interactive. They also emphasized that applying GCP principles in a real-world, skills-based environment would increase the relevance of GCP training to investigators and their delegates. Conclusion: Our findings indicate that although investigators and sponsors recognize that GCP training addresses critical tasks necessary to the quality conduct of clinical trials, they articulated the need for significant improvement in the design, content, and presentation of GCP training.

This economic evaluation aims to support policy-making on the combined use of pre-exposure prophylaxis (PrEP) with HIV vaccines by evaluating the potential cost-effectiveness of implementation that would support the design of clinical trials for assessment of combined product safety and efficacy. The target study population is a cohort of men who have sex with men (MSM) in the United States. Policy strategies considered include standard HIV prevention, daily oral PrEP, HIV vaccine, and their combination. We constructed a Markov model based on clinical trial data and published literature. We used a payer perspective, monthly cycle length, a lifetime horizon, and a 3% discount rate. We assumed a price of $500 per HIV vaccine series in the base case. HIV vaccines dominated standard care and PrEP. At current prices,PrEP was not cost-effective alone or in combination. A combination strategy had the greatest health benefit but was not cost-effective (ICER=$463,448/QALY) as compared to vaccination alone. Sensitivity analyses suggest a combination may be valuable for higher-risk men with good adherence. Vaccine durability and PrEP drug prices were key drivers of cost-effectiveness. Results suggest that boosting potential may be key to HIV vaccine value.

A face serum composed of a combination of biologically active compounds was evaluated for safety and efficacy in vitro, in a repeat insult patch test and in a human clinical efficacy trial. The serum inhibited tyrosinase activity modestly, decreased collagenase activity and exhibited notable free radical scavenging activity in vitro. It is gentle to the skin, as the serum did not irritate the skin or produce symptoms of allergic contact dermatitis in the 55 healthy adults that participated in the repeat insult patch test. In the efficacy trial, daily application of the face serum for 30 days significantly increased skin hydration, with all 35 volunteers experiencing improvement. Substantial improvements in skin elasticity, roughness (fine lines and wrinkles), and brightness also occurred during the trial. Dermatological examination also revealed a trend for reduced comedone count with use of the serum. Self-assessment responses revealed that all volunteers experienced improvements in multiple skin quality parameters and that participant perceptions are consistent with the results of the instrumental analyses. These findings indicated that the measured improvements in skin quality are not only statistically significant but are also clinically relevant as they were great enough for users of the face serum to feel and recognize.

Ionic liquids have been recognised as interesting solvents applicable in the efficient lignocellulosic biomass valorisation, especially in the biomass fractionation into individual polymeric components or direct hydrolysis some of biomass fractions. Considering the chemical character of ionic liquids, two different approaches, paved the way for a fractionation of biomass. The first strategy integrated a pre-treatment, hydrolysis and conversion of biomass through the employment of hydrogen-bond acidic 1-ethyl-3-methyimidazolim hydrogen sulfate ionic liquid. The second one relied on the use of a three-step fractionation process with hydrogen-bond basic 1-ethyl-3-methylimidazolium acetate to produce high purity cellulose, hemicellulose and lignin fractions. The proposed approaches were scrutinised for wheat straw and eucalyptus residues. Those different biomasses allowed understanding that enzymatic hydrolysis yields are dependent on the crystallinity of pre-treated biomass. The use of acetate based ionic liquid allowed to change crystalline cellulose I to cellulose II and consequently enhanced glucan to glucose yield to 93.14.1 mol% and 82.91.2 mol% for wheat straw and eucalyptus, respectively. Whereas for hydrogen sulfate ionic liquid, the same enzymatic hydrolysis yields were 61.6  0.2 mol% for wheat straw and only 7.90.3 mol% for eucalyptus residues. These results demonstrate the importance of either ionic liquid character or biomass type on the efficient biomass processing.

A vivid debate is ongoing in the scientific community about statistical malpractice and the related publication bias. No general consensus exists on the consequences and this is reflected in heterogeneous rules defined by scientific journals on the use and reporting of statistical inference. This paper aims at discussing how the debate is perceived by the agricultural economics community and implications for our roles as researchers, contributors to the scientific publication process, and teachers. We start by summarizing the current state of the p-value debate and the replication crisis, and commonly applied statistical practices in our community. This is followed by motivation, design, results and discussion of a survey on statistical knowledge and practice among the researchers in the agricultural economics community in Austria, Germany and Switzerland. We conclude that beyond short-term measures like changing rules of reporting in publications, a cultural change regarding empirical scientific practices is needed that stretches across all our roles in the scientific process. Acceptance of scientific work should largely be based on the theoretical and methodological rigor and where the perceived relevance arises from the questions asked, the methodology employed, and the data used but not from the results generated. Revised and clear journal guidelines, the creation of resources for teaching and research, and public recognition of good practice are suggested measures to move forward.

Pharmacovigilance databases are showing evidence of injury in the context of the COVID-19 modified mRNA shots. According to recent publications, adverse event reports linked to the mRNA COVID-19 products largely point to the spike protein as an aetiological agent of adverse events, but we propose that the platform itself may be culpable. To assess the safety of current and future mRNA vaccines, further analysis on the risks due to the platform itself, and not specifically the expressed antigen. If harm can be exclusively and conclusively attributed to the spike protein, then it is possible that future mRNA vaccines expressing other antigens will be safe. If harms are attributable to the platform itself, then regardless of the toxicity, or lack thereof, of the chosen payload therein, the platform may be inherently unsafe, pending modification. In this work, we examine previous studies of RNA-based delivery by a lipid nanoparticle and break down the possible etiological elements of harm.

Severe disease and uremia are risk factors for neurological complications of coronavirus disease-2019 (COVID-19). An in-depth analysis of a case series was conducted to describe the neurological manifestations of patients with COVID-19 and gain pathophysiological insights that may guide clinical decision-making – especially with respect to the cytokine release syndrome (CRS). Extensive clinical, laboratory, and imaging phenotyping was performed in five patients. Neurological presentation included confusion, tremor, cerebellar ataxia, behavioral alterations, aphasia, pyramidal syndrome, coma, cranial nerve palsy, dysautonomia, and central hypothyroidism. Neurological disturbances were remarkably accompanied by laboratory evidence of CRS. SARS-CoV-2 was undetectable in the cerebrospinal fluid. Hyperalbuminorachy and increased levels of the astroglial protein S100B were suggestive of blood-brain barrier (BBB) dysfunction. Brain MRI findings comprised evidence of acute leukoencephalitis (n = 3, of whom one with a hemorrhagic form), cytotoxic edema mimicking ischemic stroke (n = 1), or normal results (n = 2). Treatment with corticosteroids and/or intravenous immunoglobulins was attempted – resulting in rapid recovery from neurological disturbances in two cases. Patients with COVID-19 can develop neurological manifestations that share clinical, laboratory, and imaging similarities with those of chimeric antigen receptor-T cell-related encephalopathy. The pathophysiological underpinnings appear to involve CRS, endothelial activation, BBB dysfunction, and immune-mediated mechanisms.

Various tissue resident stem cells are receiving attention from basic scientists and clinicians as they hold certain promise for regenerative medicine. This paper is intended to clarify and facilitate the understanding, development and adoption of regenerative medicine in general and specifically of therapies based on unmodified, autologous adipose-derived regenerative cells (UA-ADRCs). To this end, results of landmark experiments on stem cells and stem cell therapy performed in the labs of the authors are summarized, the most intriguing of which are the following: (i) vascular associated mesenchymal stem cells (MSCs) can be isolated from different organs (adipose tissue, heart, skin, bone marrow and skeletal muscle) and differentiated into ectoderm, mesoderm and endoderm, providing significant support for the hypothesis of the existence of a small, ubiquitously distributed, universal vascular associated stem cell with full pluripotency; (ii) the orientation and differentiation of MSCs are driven by signals of the respective microenvironment; and (iii) these stem cells irrespective of the tissue origin exhibit full pluripotent differentiation potential without any prior genetic modification or the need for culturing. They can be obtained from a small amount of adipose tissue when using the appropriate technology for isolating the cells, and can be harvested from and re-applied to the same patient at the point of care without the need for complicated processing, manipulation, culturing, expensive equipment, or repeat interventions. These findings demonstrate the potential of UA-ADRCs for triggering the development of an entire new generation of medicine for the benefit of patients and of healthcare systems.

Parkinson's Disease (PD) is a neurodegenerative disorder that affects the motor system of the human body. Currently, the available treatments are limited and often have undesirable side effects. In this context, the aim of this study was to develop a novel combinational formulation of Apomorphine and Quetiapine and evaluate its efficacy in a rat model of PD. The formulation was prepared using the solvent evaporation technique and characterized for its physicochemical properties. The in-vitro drug release was evaluated using the Franz diffusion cell method, and the pharmacokinetics of the combination was studied in rats. The behavioural and biochemical parameters were evaluated in the rats using the Rotarod, pole test, and biochemical assays. The results showed that the developed formulation had satisfactory physicochemical properties and exhibited sustained drug release. The pharmacokinetic studies showed that the combination exhibited a longer residence time than the individual drugs. The behavioural and biochemical parameters showed that the combination was effective in improving motor function and reducing oxidative stress. In conclusion, the developed Apomorphine and Quetiapine combination formulation showed promising results in improving motor function and reducing oxidative stress in rat model of PD. Further studies are required to evaluate the safety and efficacy of the developed formulation in humans.

Early reports demonstrated the presence of cells with stem-like properties in bone marrow, with these cells having both hematopoietic and mesenchymal lineages. Over the years, various investigations have purified and characterized mesenchymal stromal/stem cells (MSCs) from different human tissues as cells with multi-lineage differentiation potential under the appropriate conditions. Due to their appealing characteristics and potential, MSCs are leveraged in many applications including medicine, oncology, bioprinting and as recent as treatment of COVID-19. To date, reports indicate mesenchymal stromal/stem cells have varied differentiation capabilities into different cell types and demonstrate immunomodulating and anti-inflammatory properties. Reports indicate that different MSCs microenvironments or niche and the resulting heterogeneity may influence their behavior and differentiation capacity. The potential clinical applications of mesenchymal stromal/stem cells have led to an avalanche of research reports on their properties and hundreds of clinical trials being undertaken. The future looks bright and promising for mesenchymal stem cell research with many clinical trials under way to prove their utility in many applications and in the clinic. This report provides an update on the potential broader use of mesenchymal stromal/stem cells, review early observations of the presence of these cells in the bone marrow and their magnificent differentiation capabilities and immunomodulation.

Several articles have reported that the low number of COVID-19 cases in Japan is attributed to the small number of diagnostic RT-PCR tests performed. The criticism is based on the low number of the tests performed, and they suspected there would be more potential cases in Japan. The use of pre-test probability among tested subjects is proposed in order to evaluate of the sufficiency of test availability instead of the number of the tests. The pre-test probability means the average probability, i.e., ‘suspicion level’, of having coronavirus among the tested subject in a country. The higher pre-test probability is regarded as less sufficient opportunity of the tests, and the test availability could be evaluated by the pre-test probability. Thus, potential problems of underestimation of COVID-19 cases by insufficient amount of the test would be clear by using pre-test probability. The comparison of the pre-test probability could be replaced with that of the positive rate of the test because of the linear relationship between them under the assumption of common sensitivity and specificity. Japan shows the third lowest rate (8.6%), and is considered that the considerably sufficient number of the tests have been performed. In conclusion, the positive rate of the test as a surrogate index of the pre-test probability is useful to evaluate the sufficiency of test amount instead of the number of the tests performed. In present, the potential problem of underestimation by insufficient test availability would be less serious in Japan.

Biosensors are measurement devices that can sense several biomolecules, and are widely used for the detection of relevant clinical pathogens such as bacteria and viruses, showing outstanding results. Because of the latent existing risk of facing another pandemic like the one we are living due to COVID-19, researchers are constantly looking forward to developing new technologies for diagnosis and treatment of infections caused by different bacteria and viruses. Regarding that, nanotechnology has improved biosensors design and performance through the development of materials and nanoparticles that enhance their affinity, selectivity, and efficacy in detecting these pathogens, such as employing nanoparticles, graphene quantum dots, and electrospun nanofibers. Therefore, this work aims to present a comprehensive review that exposes how biosensors work in terms of bacterial and viral detection, and the nanotechnological features that are contributing to achieving a faster yet still efficient COVID-19 diagnosis at the point-of-care.

Objectives: This study aims to identify, report, and analyze registered and published clinical trials and observational studies for the pharmacological treatment of COVID-19 conducted in China. Methods: A strategic search was conducted via the Chinese Clinical Trial Registry to identify and extract clinical trials and observational studies registered and conducted in China for the pharmacological treatment of COVID-2019 between January 1^st, 2020 and March 21^st, 2020. This was further supplemented by searches conducted via the China National Knowledge Infrastructure (CNKI) database, the MEDLINE database, the World Health Organization (WHO) database, and MedRxiv and BioRxiv electronic platforms for preprint articles, published up until April 8^th, 2020. Studies available in Chinese and English were included in the searches and extracted. A primary descriptive analysis was performed for registered clinical trials and observational studies identified in the Chinese Clinical Trial Registry based on the extraction of the following clinical study information: trial ID, planned date of enrollment, recruitment status, study design, population, sample size, intervention/exposure group, control /reference group, dosage, and primary outcomes. A secondary descriptive analysis was performed for published clinical trials and observational studies identified from the supplementary databases based on the extraction of the following published clinical study information: study design, population, intervention/exposure group, control /reference group and main results as appropriate. Results: A total of 221 clinical trials and observational studies were included from all databases searched. From the Chinese Clinical Trial Registry, 195 registered clinical studies including 170 clinical trials and 25 observational studies were identified and included for primary analysis. From the supplementary databases, 26 published clinical studies including 8 clinical trials and 18 observational studies were included for secondary analysis. Of these 26 published clinical studies, 18 studies, including 3 clinical trials and 15 observational studies were identified from CNKI, 2 studies including 1 clinical trial and 1 observational study from MEDLINE, 2 including 1 clinical trials and 1 observational studies from the WHO database, and 4 including 3 clinical trials and 1 observational studies from MedRxiv and BioRxiv platforms. In the primary analysis, among the 170 clinical trials included from the Chinese Clinical Trial Registry, 101 investigated western medicines (WMs), while 15 investigated Traditional Chinese Medicines (TCMs), and 54 investigated a combination of TCMs and WMs. Among the 25 included observational studies from the Chinese Clinical Trial Registry, 2 investigated WMs, 2 investigated TCMs, and 21 investigated a combination of TCMs and WMs. The total number of exposed patients in all 195 clinical studies from the Chinese Clinical Trial Registry amounted to 24,500. In the secondary analysis, treatment with Lopinavir-ritonavir and treatment with Hydroxychloroquine was not associated with a difference from standard of care in the rate of RT-PCR negativity; treatment with a combination of Lopinavir-ritonavir, interferon α, and Lian-Hua-Qing-Wen capsule was found to significantly improve the effective rate of treatment compared with Interferon α combined with Lian-Hua-Qing-Wen capsule. Conclusions: China is generating a massive source of evidence that is critical for defeating the COVID-19 pandemic. Not only the clinical experience, but also the scientific evidence should be shared with the global scientific community.

The transition from the Peptide/RNA world to the Protein/RNA world in the hydrothermal vent environment was a major event in the history of life. The advent of proteins utterly changed the conditions of emerging life, representing a watershed in its development. During subsequent translation various protein enzymes emerged driving protocells into a more complex and interconnected system. With their astonishing versatility, the protein enzymes catalyzed crucial biochemical reactions within protocells into more complex biomolecules in diverse metabolic pathways, whereas structural proteins provided strength and permeability in the cell membrane. Four major events followed after availability of various kinds of protein molecules during prebiotic synthesis. These are: (1) the modification of the phospholipid membrane into the plasma membrane; (2) the origin of primitive cytoplasm; (3) the beginnings of the virus world; and (4) the advent of DNA. The first innovation mediated by proteins was the improvement of the cell membrane. The phospholipid membrane was initially evolved in a vent environment from the gradual modification of a fatty acid membrane via an intermediate phosphatidate acid by non-enzymatic reactions. The phospholipid is then synthesized from phosphatidate acid by a series of enzymes. To make the phospholipid membrane more permeable, various protein molecules interacted with the cell membrane. Proteins not only stabilized the wall membrane, but also acted as pumps, preventing some molecules from the protocells from crossing the membrane barriers, while permitting other selected molecules and ions to enter and leave the protocell. The second modification led by proteins is the gradual conversion of the interior of the protocell from a water-like medium into a gel-like cytoplasm, which became the storehouse of a wide range of biomolecules including amino acids, proteins, nucleic acids, ribosomes, as well as salt and water. The third innovation utilizing the newly synthesized proteins was the emergence of the ancient virus world. In the milieu of different kinds of mRNAs in the prebiotic soup, jelly-roll capsid genes originated de novo within genomes of nonviral mRNAs by overprinting. These fragile capsid genes were possibly coated by proteins on the mineral substrate for stability and durability, transforming them into ancient viral particles. These protein coats were random and were not encoded by encased genes. Some protocells might have engulfed these viral particles, when the capsid genes utilized the ribosomes of the host to translate into the appropriate capsid proteins. These capsid proteins then coated the viral genes to make new copies of primordial viruses inside the protocell. Since then, viruses became capsid-encoding organisms. These primordial mRNA viruses parasitized RNA-based protocells, manipulating them to make new copies of themselves. This was the beginning of a relentless war between viruses and their protocellular hosts. The next stage in viral evolution was the emergence of a primitive retrovirus (pre-retrovirus) with a new kind of replicative strategy in a sense that it could turn its RNA into DNA using its own reverse transcriptase enzyme. This is the beginning of the Retro world that facilitated the transition from RNA to DNA genomes. The infection of RNA protocells with pre-retroviruses progressively transferred the RNA genome to a viral DNA genome by retro-transcription. The advent of DNA by the pre-retrovirus marks the fourth innovation, when a number of enzymes had already developed and were utilized by pre-retroviruses. With continued infection, DNA viruses slowly transferred not only their core replication enzymes, such as helicase, primase, and DNA polymerase, to RNA protocells, but also to their DNAs as well. Thus, began the DNA world, when DNA replaced RNA as the major genome of the protocells. With the advent of DNA, replication of information was entirely dissociated from its expression. Because DNA is much more stable than mRNA with more storage capacity, it is a superb archive for information systems in the form of base sequences. DNA progressively took over the replicative storage function of mRNA, leaving the latter for protein synthesis. The new protocell with the DNA genome will diversify into large populations of DNA protocells that will outcompete populations of RNA protocells. Genetic information began to flow from DNA to mRNA to protein in a two-step process involving transcription and translation. In the biological stage, DNA replication was central to the binary fission of the first cell, orchestrated by the duplication of genomes and then the division of the parent cell into two identical daughter cells. It was carried out by a set of enzymes that formed a Z-ring at the site of replication. With the onset of binary fission, the population of primitive cells grew rapidly in the hydrothermal vent environment, undergoing Darwinian evolution and diversification. These primordial hyperthermophiles, presumably the first life, obtained food and energy directly from the vent environment. However, such a situation was self-limiting, so the early cells evolved their own mechanisms for generating metabolic energy and synthesizing the molecules necessary for their reproduction. The earliest fossil record (≥ 3.5 Ga) of biotic activity is preserved in the Archean hydrothermal and sedimentary rocks of the Nuvvuagittuq Craton of Canada, the Isua Craton of Greenland, the Pilbara Craton of Australia, the Kaapvaal Craton of South Africa, and the Singhbhum Craton of India in the form of the carbonaceous remains of microbial cells, cellular microfossils, and stromatolites. These microscopic fossils provide crucial evidence of the origin and early evolution of prokaryotic cells, beginning with hyperthermophiles. Molecular phylogenetic analysis suggests that both domains of life ¬– Bacteria and Archaea probably split from the last universal common ancestor (LUCA), a hyperthermophilic organism. In the younger sequences of these Archean cratons, two kinds of photosynthetic bacteria, anoxygenic green sulfur bacteria, and oxygenic cyanobacteria, appeared in quick succession from the thermophilic ancestor, indicating a shift of niche from a benthic to a planktonic, with reduced thermotolerance. The development of anoxygenic and oxygenic photosynthesis would have allowed life to escape the hydrothermal setting and invade a newly evolved habitat—broad continental shelves to tap solar energy. Cyanobacteria invaded the global ocean, turned it into blue and green, produced oxygen for the first time, and left their signatures in the carbonates and stromatolites.

Introduction: Exams are a relatively stressful period for all students, especially undergraduate medical students. Exams bring anxiety and stress for the students. Some students experience such high stress that it hinders their academic productivity and reduces their exam performance. The aim of this study is to assess the effects of pre-exam anxiety on the academic performance of medical students. Methods: Two hundred and twenty-five final year medical students completed Westside Test Anxiety (WTA) Scale one month before their exams. Grade Point Average (GPA) of these students was noted when the results were announced. Data was processed and analyzed using SPSS v 22.0Results: The mean anxiety score on WTA scale was 3.46 ± 0.87. All students (100%) who scored ≤ 2.50 GPA were highly-extremely highly anxious. In the 2.51-3.00 GPA group, 46% were highly-extremely highly anxious, 32% were moderately anxious, and 21% had low to normal anxiety. In the 3.01-3.50 GPA group, 30% were highly-extremely highly anxious, 30% were moderately anxious, and 39% had low to normal anxiety. In the 3.51-4.00 GPA group, 29% were highly-extremely highly anxious, 23% were moderately anxious, and 47% had low to normal anxiety. The correlation coefficient between GPA and test anxiety of students was -.314 which shows inverse relationship.Conclusion: Pre-exam anxiety and stress imparts negative effects on the exam performance of final year medical students. Poor academic performance was associated with high to extremely high pre-exam anxiety while high achievers had relatively lower anxiety levels.

Human coronaviruses cause both upper and lower respiratory tract infections in humans. In 2012 a sixth human coronavirus (hCoV) was isolated from a patient presenting with severe respiratory illness. The 60-year-old man died as a result of renal and respiratory failure after admission to a hospital in Jeddah, Saudi Arabia. The aetiological agent was eventually identified as a coronavirus and designated Middle East respiratory syndrome coronavirus (MERS-CoV). MERS-CoV has now been reported in more than 27 countries across the Middle East, Europe, North Africa and Asia. As of July 2017, 2040 MERS-CoV laboratory confirmed cases, resulting in 712 deaths, were reported globally, with a majority of these cases from the Arabian Peninsula. This review summarises the current understanding of MERS-CoV, with special reference to the (i) genome structure, (ii) clinical features, (iii) diagnosis of infection and (iv) treatment and vaccine development.

The widely spread CoronaVirus Disease (COVID)- 19 is one of the worst infectious disease outbreaks in history and has become an emergency of primary international concern. As the pandemic evolves, academic communities have been actively involved in various capacities, including accurate epidemic estimation, fast clinical diagnosis, policy effectiveness evaluation and development of contract tracing technologies. There are more than 23,000 academic papers on the COVID-19 outbreak, and this number is doubling every 20 days while the pandemic is still on-going [1]. The literature, however, at its early stage, lacks a comprehensive survey from a data analytics perspective. In this paper, we review the latest models for analyzing COVID19 related data, conduct post-publication model evaluations and cross-model comparisons, and collect data sources from different projects.

The emergence of new type of viral pneumonia cases in China, on December 31, 2019; identified as the cause of human coronavirus, labeled as "COVID-19," took a heavy toll of death and reported cases of infected people all over the world, with the potential to spread widely and rapidly, achieved worldwide prominence but arose without the procurement guidance. There is an immediate need for active intervention and fast drug discovery against the 2019-nCoV outbreak. Herein, the study provides numerous candidates of drugs (either alone or integrated with another drugs) which could prove to be effective against 2019-nCoV, are under different stages of clinical trials. This review will offer rapid identification of a number of repurposable drugs and potential drug combinations targeting 2019-nCoV and preferentially allow the international research community to evaluate the findings, to validate the efficacy of the proposed drugs in prospective trials and to lead potential clinical practices.

Clinical metagenomics (CMg), referred to as the application of next-generation sequencing (NGS) to clinical samples, is a promising tool for the diagnosis of hospital-acquired pneumonia (HAP). Indeed, CMg allows identifying pathogens and antibiotic resistance genes (ARGs), thereby providing the information required for the optimization of the antibiotic regimen. Hence, provided that CMg would be faster than conventional culture, the probabilistic regimen used in HAP could be tailored faster, which should lead to an expected decrease of mortality and morbidity. While the inference of the antibiotic susceptibility testing from metagenomic or even genomic data is challenging, a limited number of antibiotics are used in the probabilistic regimen of HAP (namely beta-lactams, aminoglycosides, fluoroquinolones, glycopeptides and oxazolidinones). Accordingly in the perspective of applying CMg to the early diagnostic of HAP, we aimed at reviewing the performances of whole genomic sequencing (WGS) of the main HAP-causing bacteria (Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia and Staphylococcus aureus) for the prediction of susceptibility to the antibiotic families advocated in the probabilistic regimen of HAP.

The emergence of acute, severe non hepA–E hepatitis of unknown etiology (ASHUE) has attracted global concern owing to the very young age of the patients and its unknown etiology. Although this condition has been linked to several possible causes, including viral infection, drugs, and/or toxin exposure, the exact cause remains unknown; this makes treatment recommendations very difficult. In this review, we summarize recent updates on the clinical manifestations, complemented with laboratory results, case numbers with the global distribution and other epidemiological characteristics, and the possible etiologies. We also provide the proposed actions that could be undertaken to control and prevent further spread of this hepatitis. Since many etiological and pathological aspects of the acute non hepA–E hepatitis remain unclear, further research is needed to minimize the severe impact of this disease.

During 2019, the number of patients suffering from cough, fever and reduction of WBC’s count increased. At the beginning, this mysterious illness was called “fever with unknown origin”. At the present time, the cause of this pneumonia is known as the 2019 novel coronavirus (2019-nCoV) or the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). The SARS-CoV-2 is one member of great family of coronaviruses. Coronaviruses can cause different kind of illnesses including respiratory, enteric, hepatic, and neurological diseases in animals like cat and bat. Coronaviruses are enveloped positive-stranded RNA viruses. The SARS-CoV-2 has some particular structures for binding to host cells, reproducing itself in cells and damaging human cells. The SARS-CoV-2 can bind angiotensin-converting enzyme 2 (ACE‐2) receptors and cause various difficulties for human. The SARS-CoV-2 can cause either not-serious issues like fever and cough or serious concerns such as multi-organ failure. Source(s) of SARS-CoV-2 is under debate. Malayan pangolin and bat are the most suspicious candidate for being sources of the SARS-CoV-2. The SARS-CoV-2 can be transmitted by various ways such as transmitting from infected human to healthy human and can make severe pneumonia, which can lead to death. The SARS-CoV-2 can infect different kind of people with different ages, races, and social and economic levels. The SARS‐CoV‐2 infection can cause various sorts of clinical manifestations like cough and fever and intensity of signs and symptoms depends on sufferer conditions. Clinicians use all of available documents and tests like laboratory, histopathological and radiological findings for diagnosing new cases and curing patients with high accuracy. At the present time, there is no particular way for treating SARS-CoV-2 infection; neither antiviral drugs nor palliative agents. It seems that the best way for standing against the SARS-CoV-2 infection is preventing from it by social distancing and vaccination. This review tries to prepare an essential brief update about SARS-CoV-2 infection for clinicians.

The effect of low cycle fatigue (LCF) pre-damage on the subsequent very high cycle fatigue (VHCF) behavior is investigated in TC21 titanium alloy. LCF pre-damage is applied under 1.8% strain amplitude up to various fractions of the expected life and subsequent VHCF properties are determined using ultrasonic fatigue tests. Results show that 5% of LCF pre-damage insignificantly affects the VHCF limit due to the absent of pre-crack, but decreases the subsequent fatigue crack initiation life estimated by Pairs’ law. Pre-cracks introduced by 10% and 20% of LCF pre-damage significantly reduce the subsequent VHCF limits. The crack initiation site shifts from subsurface-induced fracture for undamaged and 5% of LCF pre-damage specimens to surface pre-crack for 10% and 20% of LCF pre-damage specimens in very high cycle region. The fracture mechanism analysis indicate that LCF pre-crack will re-start to propagate under subsequently low stress amplitude when stress intensity factor of pre-crack is larger than its threshold. Furthermore, the predicted fatigue limits based on EI Haddad model for the LCF pre-damage specimens well agree with the experimental results.

Health-related data originating from diverse sources are commonly stored in manifold databases and formats, making it difficult to find, access and gather data for research purposes. In addition, so-called secondary use scenarios for health data are usually hindered by local data codes, missing dictionaries and the lack of metadata and context descriptions. Following the FAIR principles (Findable, Accessible, Interoperable and Reusable), we developed a decentralized infrastructure to overcome these hurdles and enable collaborative research by making the meaning of health-related data understandable to both, humans and machines. This infrastructure is currently being implemented in the realm of the Swiss Personalized Health Network (SPHN), a research infrastructure initiative for enabling the use and exchange of health-related data for research in Switzerland. The SPHN ecosystem for FAIR data consists of the SPHN Dataset (semantic definitions), the SPHN RDF Schema (linkage and transport of the semantics in a machine-readable format), a project RDF template, extensive guidelines and conventions on how to generate SPHN RDF schema, a Terminology Service (converter of clinical terminologies in RDF), and a Quality Assurance Framework (automated data validation with SHACLs and SPARQLs). The SPHN ecosystem has been built in a way that it can easily be adapted and extended by any SPHN project to fit individual needs. By providing such a national ecosystem, SPHN supports researchers in generating, processing and sharing FAIR data.

Wild germplasm can be classified as the raw material essential for crop improvement. Introgression of wild germplasm is normally used in breeding to increase crop quality or resilience to evolving biotic and abiotic threats. Here, we explore the potential of introgressing Vaccinium elliottii into commercial blueberry germplasm. Vaccinium elliottii is a wild diploid blueberry species endemic to the southeastern United States that possesses highly desirable and economically important traits for blueberry breeding such as: short bloom to ripe period, adaptation to upland sandy soils, disease resistance, firmness, and pleasant flavor. To examine the potential of hybridization, we evaluated populations of interspecific hybrids across multiples stages of breeding (i.e., F1, F2, and backcrosses) in two crop seasons. We used our extensive pedigree data to generate breeding values for pre-breeding blueberry hybrid populations. Hybrid performance was evaluated considering fitness (i.e., plant vigor and plant height) in addition to evaluating six fruit-quality and marketable-related traits (i.e., size, firmness, acidity, soluble solids, weight, and yield). Overall, F2 and backcrosses rapidly achieved market thresholds, presenting values not significantly different from commercial blueberry germplasm. Our results confirmed the potential of exploiting the high genetic variability contained in V. elliotii for interspecific hybridization. Additionally, we developed germplasm resources that can be further evaluated and utilized in the breeding process, advancing selections for fruit quality and environmental adaptation.

Background: Handover is a critical process for ensuring quality and safety in healthcare. Considerable research suggests that poor handover results in significant morbidity, mortality, dissatisfaction, and excess financial costs. Despite this, little formal attention, education, and evaluation has been given to handover. There is also paucity of data on the opinions of practitioners on the safety of handover.Objectives: The aim of this study was to measure the perceived risk, degree of patient harm and the systems used to support handover, and to understand how this varied by care setting, type of clinical practice, location, or level of experience. Methods: An open, anonymous and confidential online questionnaire covering: (a) respondent characteristics; (b) peer-to-peer handover; (c) internal referrals; (d) discharges and transfers between organisations; and (e) leading and improving handover was conducted with healthcare practitioners and managers from various settings. Results: We gathered a total of 432 completed responses from 26 countries. The average reported performance of handover was rated as 3.9 out of 5.For each type of handover, 12 - 14% reported errors occurring more than weekly. Of those that knew the outcome of such errors, between 29% and 34% reported that they had witnessed moderate or severe harm. 12% and 17% of respondents believed that handover was high or very high risk (See table 4). These respondents were more likely to have witnessed moderate or severe harm, or to be more senior.A wide combination of handover systems was utilised by respondents. 28% - 32% relied exclusively on EPRs (with or without face-to-face contact). 21% used Office documents such as Word and Excel for peer-to-peer handover, and over 30% used hand-written or manual systems. Conclusions: This study suggests the need to do more — and go further — to improve communication and reduce risk during all types of handovers. Clinical leaders should find ways to train and support handover with effective systems, with less experienced staff being the primary focus. More research is needed to demonstrate the interventions that improve the safety of handover.

COVID-19 was identified in Wuhan, China in in December 2019, and rapidly spread worldwide, being declared global pandemic one month later on 30 January 2020. Since its emergence, COVID-19 has raised global concerns associated with drastic measures that were never adopted in any previous outbreak, to contain the situation as early as possible. The 2019 novel corona virus (2019-nCoV) or SARS-CoV-2 is the causative agent of COVID-19. 2019-nCoV genetic sequence was rapidly identified within few days since the first reported cases and RT-PCR kits became available for COVID-19 diagnosis. However, RT-PCR diagnosis carries a risk of false-negative results, therefore additional serologic test are needed. The most important approach in the battle against COVID-19 is rapid diagnosis of suspicious cases, timely therapeutic intervention and isolation to avoid community spread. In this review, we summarize the clinical scenario that raises suspicion of COVID-19 and available laboratory diagnostics.

Recently, there have been revolutions in the development of both gene therapy and genome surgical treatments for inherited diseases. Much of this progress has been centered around hereditary retinal dystrophies, because the eye is an immune-privileged and anatomically ideal target. Gene therapy treatments, already demonstrated to be safe and efficacious in numerous clinical trials, are benefitting from the development of new viral vectors, such as dual and triple AAVs. CRISPR/Ca9, which revolutionized the field of gene editing, is being adapted into more precise “high fidelity” and catalytically dead variants. New CRISPR endonucleases, such as CjCas9 and Cas12a, are generating excitement in the field as well. Stem cell therapy has emerged as a promising alternative, allowing human embryo derived stem cells and induced pluripotent stem cells to be edited precisely in vitro and then reintroduced into the body. This article highlights recent progress made in gene therapy and genome surgery for retinal disorders, and it provides an update on precision medicine FDA treatment trials.

Purpose: Expanded carrier screening (ECS) informs couples of their risk of having offspring affected by certain genetic conditions. Limited data exists assessing the actions and reproductive outcomes of at-risk couples (ARCs). We describe the impact of ECS on planned and actual pregnancy management in the largest sample of ARCs studied to date. Methods: Couples who elected ECS and were found to be at high risk of having a pregnancy affected by at least one of 176 genetic conditions were invited to complete a survey about their actions and pregnancy management. Results: Three hundred ninety-one ARCs completed the survey. Among those screened before becoming pregnant, 77% planned or pursued actions to avoid having affected offspring. Among those screened during pregnancy, 37% elected prenatal diagnostic testing (PNDx) for that pregnancy. In subsequent pregnancies that occurred in both the preconception and prenatal screening groups, PNDx was pursued in 29%. The decision to decline PNDx was most frequently based on the fear of procedure-related miscarriage, as well as the belief that termination would not be pursued in the event of a positive diagnosis. Conclusions: ECS results impacted couples’ reproductive decision-making and led to altered pregnancy management that effectively eliminates the risk of having affected offspring.

Steroid analysis is important in the clinical assessment of endocrine function in health and disease. Although tandem mass spectrometry methods coupled with chromatographic separation are considered the gold standard analytical technique in this setting, enabling profiling of multiple steroids in a single sample, sample processing can be labour-intensive. Here we present a simple, efficient automated 96-well Supported Liquid Extraction method with dichloromethane/isopropanol as organic solvent, carried out on a Extrahera automated sample handler (Biotage), which completes sample preparation of 80 plasma samples (200µL) in 90 minutes. Compounds were separated on a Kinetex C18 column (150x3mm;2.6um) using a mobile phase of methanol and water (0.1% formic acid). The run time was 16 minutes on a Nexera uHPLC system (Shimadzu) with a QTrap 6500+ linear ion trap mass spectrometer (AB Sciex). Precisions ranged 8.1 to 18.1% RSD, bias -10.1-5.8%, and extraction recoveries 73.5-111.9%. LOQs ranged between 0.025–0.500 ng/mL.

This study evaluated the effect of low-level laser irradiation induces by diode laser on the speed of orthodontic tooth movement of canines submitted to initial retraction. Twenty-four mandibular canines were retracted by using NiTi spring (force of 150 g/side). Thirteen of those were irradiated with a diode laser 980-nm diode laser (Wiser Laser Doctor Smile, Lambda) operating at an 810-nm wavelength (1 W of output power, continuous wave of 66.7 J/cm2) that was equipped with a 0.6-mm optical fiber in continuous-wave mode. The canine retraction was accomplished by using prefabricated coil springs. The right of the mandible was chosen to be irradiated with the laser, whereas the left side was considered the control without laser irradiation. The laser was applied with 0-, 3-, 7-, and 14-day intervals. The amount of canine retraction was measured with a digital electronic caliper while the pain level was prompted by a patient questionnaire. The speed of tooth movement was significantly greater in the laser group than in the control group. The pain intensity was also at a lower level in the laser group. Our findings suggest that diode laser therapy can highly accelerate tooth movement during orthodontic treatment and can also effectively reduce pain level.

Clinical agreement between two quantitative measurements on a group of subjects is generally assessed with the help of the Bland-Altman (B-A) limits. The interpretation regarding agreement is based on whether B-A limits are within the pre-specified clinical tolerance. Thus, clinical tolerance limits are necessary for this method. We argue in this communication that such limits of clinical tolerance can be directly used for assessing agreement and plead that this nonparametric approach is simple and robust to the distribution pattern and outliers. Such direct use of clinical tolerance limits has more flexibility, and it is more effective in assessing the extent of agreement.

The “Crisis of Reproducibility” has received considerable attention both within the scientific community and without. While factors associated with scientific culture and practical practice are most often invoked, I propose that the Crisis of Reproducibility is ultimately a failure of generalization with a fundamental scientific basis in the methods used for biomedical research. The Denominator Problem describes how limitations intrinsic to the two primary approaches of biomedical research, clinical studies and pre-clinical experimental biology, lead to an inability to effectively characterize the full extent of biological heterogeneity, which compromises the task of generalizing acquired knowledge. Drawing on the example of the unifying role of theory in the physical sciences, I propose that multi-scale mathematical and dynamic computational models, when mapped to the modular structure of biological systems, can serve a unifying role as formal representations of what is conserved and similar from one biological context to another. This ability to explicitly describe the generation of heterogeneity from similarity addresses the Denominator Problem and provides a scientific response to the Crisis of Reproducibility.

Health information technology has been widely used in healthcare, which has contributed a huge amount of data. Health data has four characteristics: high volume; high velocity; high variety and high value. Thus, they can be leveraged to i) discover associations between genes, diseases and drugs to implement precision medicine; ii) predict diseases and identify their corresponding causal factors to prevent or control the diseases at an earlier time; iii) learn risk factors related to clinical outcomes (e.g., patients’ unplanned readmission), to improve care quality and reduce healthcare expenditure; and iv) discover care coordination patterns representing good practice in the implementation of collaborative patient-centered care. At the same time, there are major challenges existing in data-driven healthcare research, which include: i) inefficient health data exchanges across different sources; ii) learned knowledge is biased to specific institution; iii) inefficient strategies to evaluate plausibility of the learned patterns and v) incorrect interpretation and translation of the learned patterns. In this paper, we review various types of health data, discuss opportunities and challenges existing in the data-driven healthcare research, provide solutions to solve the challenges, and state the important role of the data-driven healthcare research in the establishment of smart healthcare system.

Clinical education is a method that is applied to formal nurse education as a step to provide real and direct learning experiences in the nursing environment correctly and effectively. The success of education in a clinical setting certainly requires the support of teaching nurses (clinical instructors) who have credibility and competence in terms of knowledge, attitudes and skills and are actively involved in professional activities. The diversity of backgrounds of nurses and students, including patients, certainly contributes to a shift in paradigms and perspectives for the nursing environment both in education and in clinical settings in health services. Responding to this cultural diversity, it is important to prepare knowledge and understanding related to transcultural nursing issues, intercultural communication and clinical education which explores the socio-cultural elements in the implementation of staff, students and patients. Purpose: The purpose of this literature review is to identify the extent to which nurse educators play a role by including socio-cultural and transcultural aspects in efforts to develop the quality of education in clinical practice environments in the millennium era. Method: The method of writing this article uses 11 literature review, the publication year period 2019,2020 and 2021 with sources from 4 databases such as science Direct, Scopus, ProQues and Elsevier. The review guidelines used are based on Prisma and the Joanna Briggs Institutute. The level of eligibility is identified through the title, abstract, research methodology as well as the type of scholarly journal and full text. Results: The results of the reviews found are presented in a narrative form. The results of the review study found that there were 11 articles explaining the competence of clinical education based on the socio-cultural approach, which is an educational strategy in the clinical area that integrates transcultural elements of nursing, intercultural communication, collaboration, self-directed with the principles of openness, honesty, and mutual respect in the implementation of team interaction and collaboration. The development of interpersonal relationships is also an important role that educators must have in helping to introduce the nurse orientation process to the organizational environment and other professional teams so that the achievement of satisfaction with clinical education is able to improve the performance of nurses and students perfectly. Conclusion: Clinical education which is supported by the competence of nurse educators (clinical instructors) who have individual and professional competences has a role to play in improving clinical learning outcomes by both students and nurses with a socio-cultural and transcultural strategic approach that will create satisfaction with the achievement of clinical competence and performance effectively.

The basic principles of geological risk calculation through Probability of Success (PoS) are mostly applied for numerical estimation of additional hydrocarbon existence in proven reservoirs or potential hydrocarbon discoveries in selected geological regional subsurface volume. It can be tailored and validated for a comprehensive input dataset collected in the selected petroleum province, adapted by dividing up geological events into several probability categories and classes. The most applied categories are (existence of) reservoir rocks, traps and isolators, source rocks, migration pathways and preservation conditions for hydrocarbons The methodology results in unique probability values as multiplication of independent statistical events, which can also be applied in the assessment of a potential hydrocarbon discovery of desired minimal volume and its value in any virtual currency like risk-neutral dollars. Such methodology has been extensively developed in the last decades in the Croatian subsurface, mostly in the Croatian part of the Pannonian Basin System (CPBS). Through the adaptation of geological categories, it was also applied in hybrid, i.e., stochastical, models developed in the CPBS (Drava Depression). Stochastically estimation of porosity was already applied. As the robustness of this methodology is very high, it was also modified to estimate the influence of water-flooding in increasing oil recovery in some proven Neogene sandstone reservoirs in the CPBS (Sava Depression). This new modification is being presented to be applied to geological risk calculation, intending to assess the safety of geological environment in deep wells, where depleted radioactive fuel would be disposed, a subject of great importance. The case study encompassed the magmatic and metamorphic rocks in the pre-Neogene basement of the CPBS. For disposal purpose, these are regionally lithologies considered as to be the safest ones considering petrophysical values, water saturation, recent weathering and tectonic activity.

Chronic diseases are still known as incurable diseases, and we suspect that the medical research model is unfit for characterizing chronic diseases. In this study, we examined accuracy and reliability required for characterizing chronic diseases, reviewed implied presumptions in clinical trials and assumptions used in statistical analysis, examined sources of variances normally encountered in clinical trials, and conducted numeric simulations by using hypothetical data for several theoretical and hypothetical models. We found that the sources of variances attributable to personal differences in clinical trials can distort hypothesis test outcomes, that clinical trials introduce too many errors and too much inaccuracies that tend to hide weak and slow effects of treatments, and that the means of treatments used in statistical analysis have little or no relevance to specific patients. We further found that a large number of uncontrolled co-causal or interfering factors normally seen in human subjects can greatly enlarge the means and the variances of the experimental errors, and the use of high rejection criteria (e.g., low p values) further raises the chances of failing to find treatment effects. As a whole, we concluded that the research model using clinical trials is wrong on multiple grounds, under any of our realistic theoretical and hypothetical models, and that misuse of statistical analysis is most probably responsible for failure to identify treatment effects for chronic diseases and to detect harmful effects of toxic substances in the environment. We proposed alternative experimental models involving the use of single-person or mini optimization trials for studying low-risk weak treatments.

Over a year into the COVID-19 pandemic, there is growing evidence that SARS-CoV-2 infections among dogs are more common than previously thought. In this study, the prevalence of SARS-CoV-2 antibodies was investigated in two dog population. The first group was comprised of 1069 dogs admitted to the Veterinary Teaching Hospital for any given reason. The second group included dogs that shared households with confirmed COVID-19 cases in humans. This study group numbered 78 dogs. In COVID-19 infected households, 43.9% tested ELISA positive, and neutralisation antibodies were detected in 25.64% of dogs. Those data are comparable with the secondary attack rate in the human population. With 14.69% of dogs in the general population testing ELISA positive, there was a surge of SARS-CoV-2 infections within the dog population amid the second wave of the pandemic. Noticeably seroprevalence of SARS-CoV-2 in the dog and the human population did not differ at the end of the study period. Male sex, breed and age were identified as significant risk factors. This study gives strong evidence that while acute dog infections are mostly asymptomatic, they can pose a significant risk to dog health. Seropositive dogs had a 1.97 times greater risk for developing central nervous symptoms.

Increasing rates of infection by antibiotic resistant bacteria have led to a resurgence of interest in bacteriophage (phage) therapy. Several phage therapy studies in animals and humans have been completed over the last two decades. We conducted a systematic review of safety and toxicity data associated with phage therapy in both animals and humans reported in English-language publications from 2008 – 2021. Overall, 69 publications met our eligibility criteria including 20 animal studies, 35 clinical case reports or case series, and 14 clinical trials. After summarizing safety and toxicity data from these publications, we discuss potential approaches to optimizing safety and toxicity monitoring with the therapeutic use of phage moving forward. In our systematic review of the literature, we found few, but no serious, adverse events associated with phage therapy. Comprehensive and standardized reporting of potential toxicities associated with phage therapy has generally been lacking in the published literature. Structured safety and tolerability endpoints are necessary when phages are administered as anti-infective therapeutics.

Modern medicine adopted four presumptions when it evolved from ancient experienced-based mind-body medicine. To understand its failure in finding cures for chronic diseases, we examined four presumptions, and found that statistical population of health properties does not exist for most research purposes, mathematical models are misused to model intensive properties, synthetic drugs are inherently more dangerous than nature-made medicines under their respective application conditions, and reductionist treatments are inferior and inherently dangerous. We found that clinical trials are valid only for research where treatment effect is much stronger than the total effects of all interfering or co-causal factors or errors introduced by misused mathematical models can be tolerated. In all other situations, clinical trials introduce excessive errors and fail to detect treatment effects, or produce biased, incorrect or wrong results. We further found that chronic diseases are manifestation of small departures in multiple process attributes in distinctive personal biological pathways networks, that modern medicine lacks required accuracy for accurately characterizing chronic diseases, and that reductionist treatments are good at controlling symptoms and safe for short term uses. For all stated reasons, as long as modern medicine continues relying on the flawed presumptions, it can never find predictable cures for chronic diseases. By implication, predictable cures to chronic diseases are adjustments to lifestyle, dietary, emotional, and environmental factors to slowly correct departures in process attributes responsible for chronic diseases.

Global food security for the increasing world population not only requires increased sustainable production of food but a significant reduction in pre- and post-harvest waste. The timing of when a fruit is harvested is critical for reducing waste along the supply chain and increasing fruit quality for consumers. The early in field assessment of fruit ripeness and prediction of the harvest date and yield by non-destructive technologies have the potential to revolutionize farming practices and enable the consumer to eat the tastiest and freshest fruit possible. A variety of non-destructive techniques have been applied to estimate the ripeness or maturity but not all of them are applicable for in situ (field or glasshouse) assessment. This review focuses on the non-destructive methods which are promising, or have already been, applied to the pre-harvest in field measurement including colorimetry, visible imaging, spectroscopy and spectroscopic imaging. Machine learning and regression models used in assessing ripeness are also discussed.

Shells, probably like no other product of nature, have played an important role in the history of mankind. The pre-Hispanic civilizations of Ibero-America also used certain type of shells profusely in their religious ceremonies, in particular, in Ecuador there were two species of main importance, the Spondylus princeps and the Spondylus calcifer broadly employed to manufacture ornaments that possess a strong symbolic, religious and social meaning and that were almost exclusively used by ruling classes. Among these ornaments, the faces carved on the Spondylus shells are little known. In the present study, we chose a total of fifteen (15) pieces from the Pastor Restrepo Lince´s archaeomalacology collection to understand the possible uses of these objects, through the interpretation of the gestures represented on the faces, their dimensions, and their geographical distribution in pre-Hispanic Ecuador. To achieve the proposed objective, we approach the present investigation from the perspective of the formal analysis of concepts, which is a mathematical theory of representation of knowledge, finding that these faces carved in Spondylus, were used daily or in special ceremonial occasions and that its use was common in all the regional cultures of ancient Ecuador, from the oldest such as Valdivia, and for more than 2000 years, indicating a long tradition of the use of Spondylus as an object of great symbolic and economic value until the arrival of the Spanish

Calibrating ecological models or making decisions with them is an optimisation problem with challenging methodological issues. Depending on the optimisation formulation, there may be a large variety of optimisation configurations (e.g. multiple objectives, constraints, stochastic criteria) and finding a single acceptable solution may be difficult. The challenges are exacerbated by the high computational cost and the non linear or elusive mathematical properties that increased with the complexity of numerical models. From the feedbacks of practitioners, the need for a guideline for conducting optimisation of complex models has emerged. In this context, we propose a practical guide for the complex model optimisation process, covering both calibration and decision-making. The guide sets out the workflow with recommendations for each step based on existing tools and methods usually scattered throughout the literature. This guide is accompanied with an ODDO template (Overview, Design, Details of Optimisation) to standardise the published description of model-based optimisation and suggests research directions.

Objective. To describe patient satisfaction with pre-hospital emergency knowledge and determine if patients and professionals share a common vision on the satisfaction predictors. Methods. A qualitative study conducted in two phases. First, a systematic review following the PRISMA protocol was carried out searching publications between January 2000 and July 2016 in Medline, Scopus, and Cochrane. Second, three focus groups involving professionals (advisers and healthcare providers) and a total of 79 semi-structured interviews involving patients were conducted to obtain information about what dimensions of care were a priority for patients. Results. Thirty-three relevant studies were identified. A majority conducted in Europe using questionnaires. They pointed out a very high level of satisfaction of callers and patients. Delay with the assistance and the ability for resolution of the case are the elements that overlap in fostering satisfaction. The published studies neither reviewed the overall care process nor related the measurement of the real time in responding to an emergency with the satisfaction. The patients and professionals concurred in their assessments about the most relevant elements for patient satisfaction, although safety was not a predictive factor for patients. Response capacity and perceived capacity for resolving the situation were crucial factors for satisfaction. This qualitative approach yielded assistance targets to be improved. Conclusions. Published studies have assessed similar dimensions of satisfaction. Furthermore, despite the fact that few explanations may be given due to the no face to face attention, taking into account the patient’s emotional needs or maintaining contact with the patient until the emergency services arrive are high predictors of the satisfaction.

A cross-sectional study was carried out to determine the prevalence of subclinical mastitis (SCM) among medium to large scale household dairy farms in southwestern district, Jhenaidah, Bangladesh during July to December 2019. A total of 78 (n=100) lactating cows from household dairy farms (N=32) having three or more dairy cows were selected randomly as sampled populations. Milk samples were screened for SCM by using Surf Field Mastitis Test (SFMT). The prevalence of SCM varied among farm level [71.9% (95% CI: 53.3-86.3)], individual animal level [67.9% (95% CI: 56.4-86.3)] and quarter level [29.5% (95% CI: 24.5-34.9)]. Descriptive statistics represented the farmers and farm demography, characteristics of the sampled population, and overall management feature. Random Effect Logistic Regression identified, Body Condition Score (BCS) [OR=3.8 and 2.9, at cows level and quarter level respectively (BCS-2 vs. BCS-≥3)], and breed [OR=5.1 and 2.9, at cows level and quarter level respectively (HF× Sahiwal vs. HF × Local)] as potential risk factors. This study shows that SCM is highly prevalent in the study area, which is a major threat to the dairy industry's production performance. Regular screening by SFMT, proper hygiene, improve the management system, and farmer’s awareness is required to control the disease.

Direct and indirect anthropogenic factors play a massive role in driving wildlife species towards extinction. Longitudinal retrospective studies identify key ‘factors’ responsible for the decline in numbers of wildlife, however, lack the reasoning behind the events leading to mortality. The overarching aim of this study was to categorize these ‘factors’ into different stressor categories faced by reptiles to understand its impact on an individual, and to compare how each stressor category influences the survival of an individual. The results from this study indicated that almost half of the number of reptiles being hospitalized were due to exposure to preliminary stressors such as lawn mowing incidents and pet attack. Primary and secondary admissions were fairly equal in number, however the mortality rate for secondary admissions was drastically high (~80%). The discussion integrates species’ ecology and stress physiology which can prove to have multi-faceted benefits across the fields of ecology and animal welfare. Ecologists can use the results from this study to comprehend species’ activity patterns to better plan reptilian conservation programs, whereas, for wildlife clinicians and rehabilitators, assignment of stressor categories could be a beneficial tool for bolstering the welfare monitoring program for small native reptiles in clinical settings.

(1) Background: the NGS based mutational study of hereditary cancer genes is crucial to design tailored prevention strategies in subjects with different hereditary cancer risk. The ease of amplicon-based NGS library construction protocols contrasts with the greater uniformity of enrichment provided by capture-based protocols and so with greater chances for detecting larger genomic rearrangements and copy-number variations. Capture-based protocols, however, are characterized by a higher level of complexity of sample handling, extremely susceptible to human bias. Robotics platforms may definitely help dealing with these limits, reducing hands-on time, limiting random errors and guaranteeing process standardization. (2) Methods: We implemented and validated the complete automation of the SOPHiA GENETICS’ CE-IVD Hereditary Cancer Solution™ (HCS) libraries preparation workflow on the Hamilton’s STARlet platform. (3) Results: We demonstrate that this automated workflow, used for more than 1000 samples achieved the same performances of manual setup in terms of coverages and reads uniformity, with extremely lower variability of reads mapping rate onto the regions of interest. (4) Conclusions: This automated solution offers same reliable and affordable NGS data, but with the essential advantages of a flexible, automated and integrated framework, minimizing possible human errors and depicting a laboratory’s walk-away scenario.

The emergence of proteins in the prebiotic world was a watershed event at the origin of life. With their astonishing versatility, the protein enzymes catalyzed crucial biochemical reactions within protocells into more complex biomolecules in diverse metabolic pathways, whereas structural proteins provided strength and permeability in the cell membrane. Five major biochemical innovations followed in succession after availability of various kinds of protein molecules during decoding and translation of mRNAs. These are: (1) the modification of the phospholipid membrane into the plasma membrane; (2) the origin of primitive cytoplasm; (3) primitive gene regulation; (4) the beginnings of the virus world; and (5) the advent of DNA. The creative role of viruses during prebiotic synthesis led to the origin of the DNA world, when DNA replaced mRNA as the major genome of the protocells. With the advent of DNA, replication of information was entirely dissociated from its expression. Because DNA is much more stable than mRNA with more storage capacity, it is a superb archive for information systems in the form of base sequences. DNA progressively took over the replicative storage function of mRNA, leaving the latter for protein synthesis. Genetic information began to flow from DNA to mRNA to protein in a two-step process involving transcription and translation. In the biological stage, DNA replication was central to the binary fission of the first cell, orchestrated by the duplication of genomes and then the division of the parent cell into two identical daughter cells. With the onset of binary fission, the population of primitive cells grew rapidly in the hydrothermal vent environment, undergoing Darwinian evolution and diversification by mutation. The habitat of the earliest fossil record (≥ 3.5 Ga) from the Archean sedimentary rocks of Canada, Greenland, Australia, South Africa, and India offers a new window on the early radiation of microbial life. The development of anoxygenic and then oxygenic photosynthesis from early hyperthermophiles would have allowed life to escape the hydrothermal setting to the mesophilic global ocean.

Coronavirus disease 2019 (COVID-19) caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has reached a global epidemic across the world after first reported in Wuhan, China’s Hubei province in December 2019. The pandemic is also associated with acute respiratory distress syndrome (ARDS) characterized by excess inflammation, progressive arterial hypoxemia and dyspnea. Mesenchymal stem/ stromal cells (MSCs) have been investigated as treatment for ARDS due to immunomodulatory property. Exosomes derived from MSCs play an important role in paracrine signaling of MSCs, thereby contributed to immunomodulation of the immune microenvironment. Exosomes are emerged as potential alternative to MSC cell therapy with superiority of safety. In this review, we will introduce MSC-derived exosomes and briefly discuss current progress on MSCs and exosomes in ARDS, which may have clinical implications in pathogenesis and treatment of COVID-19.

Genetic testing allows for identification of germline DNA variations which are associated with a significant increase in risk of developing breast and ovarian cancer. Detection of a BRCA1 or BRCA2 pathogenic variant triggers several clinical management actions, which may include increased surveillance and prophylactic surgery for healthy carriers or treatment with PARP inhibitor therapy for carriers diagnosed with cancer. Thus, standardized validated criteria for annotation of BRCA1 and BRCA2 variants according to their pathogenicity are necessary to support clinical decision making and ensure improved outcomes. Upon detection, variants whose pathogenicity can be inferred by the genetic code are typically classified as pathogenic, likely pathogenic, likely benign, or benign. Variants whose impact on function cannot be directly inferred by the genetic code are labeled as Variants of Uncertain Clinical Significance (VUS) and are evaluated by multifactorial likelihood models that use personal and family history of cancer, segregation data, prediction tools, and co-occurrence with a pathogenic BRCA variant. Missense variants, coding alterations that replace a single amino acid residue with another, are a class of variants for which determination of clinical relevance is particularly challenging. Here, we discuss current issues in variant classification by following a typical life cycle of a BRCA1 missense variant through detection, annotation and information dissemination. Advances in massively parallel sequencing have led to a substantial increase in VUS findings. Although comprehensive assessment and classification of missense variants according to their pathogenicity remains the bottle neck, new developments in functional analysis, high throughput assays, data sharing, and statistical models are rapidly changing this scenario.

A case report of the diagnosis of Long Term Sequelae of West Nile Neuroinvasive Disease in a patient with 9 years history. Empirical data of symptoms and test reports has been presented and based on the available data likely pathogenesis of the disease has been discussed. The empirical data has been compared to the published literature to reach a highly confident diagnosis.

Despite great strides being achieved in improving cancer patients’ outcomes through better therapies and combinatorial treatment, several hurdles still remain due to therapy resistance, cancer recurrence and metastasis. Drug resistance, culminating in relapse and metastatic disease continue to be associated with fatal disease. Cancer stem cells (CSCs) are a subpopulation of cancer cells known to be resistant to therapy and cause metastasis. Whilst the debate on whether CSCs are the origins of the primary tumor rages on, CSCs have been further characterised in many cancers with data illustrating that CSCs display great abilities to self-renew, withstand therapies due to enhanced epithelial to mesenchymal (EMT) properties, enhanced expression of ABC membrane transporters, activation of several survival signaling pathways and increased immune evasion DNA repair mechanisms. CSCs also display great heterogeneity with the consequential lack of specific CSC markers presenting a great challenge to their targeting. In this updated review we re-visit CSCs within the tumor microenvironment (TME) and present novel treatment strategies targeting CSCs. These promising strategies include targeting CSCs-specific properties using small molecule inhibitors, immunotherapy, microRNA mediated inhibitors, epigenetic methods as well as targeting CSC niche-microenvironmental factors and differentiation. Lastly, we present recent clinical trials undertaken to try to turn the tide against cancer by targeting CSC-associated drug resistance and metastasis.

Repeated air pollution exposure is one of the major threats to skin health. Air pollution causes skin damage and accelerates skin ageing mainly through oxidative stress mechanisms. Since it is difficult to minimize skin exposure from air pollutants, especially in urban areas, strategies to protect the skin are needed. On the other hand, plant phenolic compounds have been found to be effective in attenuating cellular oxidative stress and inflammation induced by different air pollutants. Therefore, we conducted a 12-week randomized, placebo-controlled, double blind study to assess the efficacy of a polyphenol-enriched dietary supplement (comprised of olive leaf, lemon verbena, rosemary and Sophora japonica extracts) in reducing pollution-induced oxidative stress and in improving different skin parameters related to skin ageing of Caucasian and Asian volunteers living in a polluted urban European area (Milan). One hundred healthy women were recruited and randomized in the placebo or in the test dietary supplement treatment arms. To assess the efficacy of the dietary supplement, the total antioxidant capacity on saliva (FRAP) was determined, as well as the oxidative damage on skin (lipoperoxides content), the skin moisture (corneometry), the trans-epidermal water loss (Tewameter), the skin radiance and the skin colour, (spectrophotometry), the skin elasticity (cutometry), the skin sebum content (sebumeter), and the skin roughness (image analysis). As a result, both inter-group and intra-group analysis proved that the dietary supplement improved all clinical and biochemical monitored parameters, in both Caucasian and Asian individuals. In conclusion, the results of the study indicate a reduced oxidative stress-induced skin damage in both Asian and Caucasian women living in a polluted urban area.

Despite all scientific efforts and many protracted and expensive clinical trials, no new drug has been approved by FDA for treatment of Alzheimer disease (AD) since 2003. Indeed, more than 200 investigational programs have failed or have been abandoned in the last decade. The most probable explanations for failures of disease-modifying treatments (DMTs) for AD may include late initiation of treatments during the course of AD development, inappropriate drug dosages, erroneous selection of treatment targets, and mainly an inadequate understanding of the complex pathophysiology of AD, which may necessitate combination treatments rather than monotherapy. Clinical trials’ methodological issues have also been criticized. Current drug-development research for AD is aimed to overcome these drawbacks. Preclinical and prodromal AD populations, as well as traditionally investigated populations representing all the clinical stages of AD, are included in recent trials. Systematic use of biomarkers in staging preclinical and prodromal AD and of a single primary outcome in trials of prodromal AD are regularly integrated. The application of amyloid, tau, and neurodegeneration biomarkers, including new biomarkers—such as Tau positron emission tomography, neurofilament light chain (blood and CSF biomarker of axonal degeneration) and neurogranin (CSF biomarker of synaptic functioning)—to clinical trials allows more precise staging of AD. Additionally, use of the Bayesian statistics, modifiable clinical trial designs, and clinical trial simulators enrich the trial methodology. Besides, combination therapy regimens are currently assessed in clinical trials. The abovementioned diagnostic and statistical advances, which have been recently integrated in clinical trials, are consequential to the recent failures of studies of disease-modifying treatments. Their experiential rather than theoretical origins may better equip potentially successful drug-development strategies.

Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer deaths worldwide. Surgery or surgery plus radiotherapy and/or chemotherapy for patients with metastatic CRC (mCRC) were accepted as the main therapeutic strategies until the early 2000s, when targeted drugs, like cetuximab and bevacizumab were developed. The use of targeted drugs in clinical practice has significantly increased patients’ overall survival. To date, the emergence of several types of targeted drugs has opened new possibilities and revealed new prospects for mCRC treatment. Therapeutic strategies are continually being updated to select the most suitable targeted drugs based on the results of clinical trials that are currently underway. This review discusses the up-to date molecular evidence of targeted therapy for mCRC and summarizes the Food and Drug Administration-approved targeted drugs including the results of clinical trials. We also explain their mechanisms of action and how these affect the choice of a suitable targeted therapy.

Background: A growing number of clinical practice guidelines (CPGs) with regards to non-pharmacological interventions for breast cancer survivors are available. However, given the limitations in guideline development methodologies and inconsistency of recommendations, it remains uncertain how best to design and implement such non-pharmacological strategies to tailor interventions for breast cancer survivors with varied health conditions, healthcare needs, and preferences. Aim: To critically appraise and summarise available non-pharmacological interventions for symptom management and health promotion that can be self-managed by breast cancer survivors based on the recommendations of the CPGs. Methods: Clinical practice guidelines which were published between January 2016 and September 2021 and described non-pharmacological interventions for breast cancer survivors were systematically searched in six electronic databases, nine relevant guideline databases, and five cancer care society websites. The quality of the included CPGs was assessed by four evaluators using the Appraisal of Guidelines for REsearch and Evaluation, second edition tool. Content analysis was conducted to synthesise the characteristics of the non-pharmacological interventions that were recommended by the included CPGs, such as the intervention’s form, duration and frequency, level of evidence, grade of recommendation, and source of evidence. Results: Fourteen CPGs were identified and analysed. Of the 14 CPGs appraised, only five were rated as high quality. The domain with the highest standardised percentage was “scope and purpose” (84.61%), while the “applicability” domain had the lowest standardised percentage (51.04%). Five guidelines were assessed as “recommended”, seven were rated as “recommended with modifications”, and the remaining two were considered “not recommended”. Regarding the content analysis, physical activity/exercise, meditation, hypnosis, yoga, music therapy, stress management, relaxation, massage, and acupressure were the common self-managed non-pharmacological interventions recommended by the 14 CPGs. Physical activity/exercise was the only self-managed non-pharmacological intervention that was mostly recommended for psychological and physical symptom management by the included CPGs. However, there were significant disparities in terms of level of evidence and grade of recommendation in the included CPGs. Conclusion: The recommendations for the self-managed non-pharmacological interventions were varied and limited among the 14 CPGs, and some were based on medium- and low-quality evidence. More rigorous methods are required to develop high-quality CPGs in order to guide clinicians in offering high-quality and tailored breast cancer survivorship care.

Oats represents a promising alternative to small-grain cereals from Triticeae group (wheat, barley, rye) for persons suffering from any form of gluten intolerance, especially celiac disease (CD), since oat-specific prolamins avenins reveal generally lower gluten content and immunoreactivity. Recent studies on avenin molecular structure revealed large genetic variability in avenin sequences affecting the spectrum of gluten peptides produced by hydrolases in human digestive tract. The aim of the present review is to summarise recent knowledge obtained in laboratory in vitro studies focused on the effect of avenin-derived peptides on reactivity of crucial components of human immune system such as dendritic cells (DC) and T-cells. The other part of the review summarises the results of clinical studies with CD patients including oat products in their diet. Since different clinical studies revealed contradictory results regarding potential safety of oats for CD patients, the focus has to be directed at genetic variability in oat avenins. Identification of avenin isoforms with minimum CD immunoreactivity will open up ways leading to designing novel oat cultivars suitable for CD patients. Knowledge on immunoreactivity of gluten peptides together with breeding new oat cultivars revealing minimum avenin immunoreactivity with respect to CD as well as application of food processing technologies leading to gluten content reduction should result in development of gluten-free oats safe for celiacs.

The Clinical Trials Transformation Initiative (CTTI) Investigator Qualification Project addresses the need for a more efficient and effective means of identifying qualified clinical investigators and delegates. Selection of investigators and delegates who are qualified by training and experience to conduct clinical trials is essential to safeguarding protections for study participants and ensuring data quality and integrity. Sponsors generally document investigator qualification through training on the principles of good clinical practice (GCP), as defined by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), adopted by regulatory authorities in the US, Japan and the European Union. Although these GCP principles provide an important foundation for promoting the conduct of quality clinical trials, the industry standard “one-size-fits-all” GCP training may not fully prepare investigators and delegates for conducting quality clinical trials. Routine GCP training alone may not be sufficient to prepare an inexperienced member of a site team, while repeating such training is unlikely to enhance the qualifications of an experienced researcher. The CTTI project team used findings from qualitative research activities, as well as input from an expert meeting with multiple stakeholders, to identify gaps and redundancies in the current training of investigators and their delegates and recommend practical, action-based solutions. CTTI provides recommendations on how to implement a more efficient and effective means of qualification for investigators and delegates, determine whether a site team is a good fit for a particular protocol, and improve the quality of clinical trial conduct.

Background: Cardiomyopathy is commonly observed disease that may occurs due to mutations in either susceptible genes or modifier gene. People with broad age group are affected either attributable to spontaneous or inherited mutations of these genes. Various gene mutations are reported so far but only few of them were studied in detail. Methods: In the current study, we evaluated epidemiological variables like age, sex, familial status, parental consanguinity. We also described specific clinical symptoms associated with the cardiomyopathy condition in Indian population. Results: Our studies on mutation screening of phospholamban gene revealed two transitions (4880 C/T, 4887 T/G) in 5’ flanking region which might cause inherited dilated cardiomyopathy with refractory congestive heart failure are We further deliberated the gene polymorphism of renin angiotensin system gene angiotensin-1-converting enzyme as an associated marker/ modifier in cardiomyopathy patients and their family members. Conclusions: Information on epidemiological, clinical statistics, phospholamban gene mutation analysis and angiotensin-1-converting enzyme gene polymorphism is essential to guide the successful execution for future therapies and benefits us to identify those patients at risk for faster disease progression, congestive heart failure, and arrhythmia.

Over the course of the pandemic due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), multiple new clinical manifestations, as the consequence of the tropism of the virus, have been recognized. That includes now the neurological manifestations and conditions, such as headache, encephalitis, as well as olfactory and taste disorders. We present a series of ten cases of RT-PCR confirmed SARS-CoV-2 infected patients diagnosed with viral-associated olfactory and taste loss from four different countries.

Clinical training in medical schools in Spain is performed by rotations in university hospitals. During these internships, students are expected to acquire and master basic procedural skills. However, the assessment tools available rarely check whether these skills are completely acquired by the students. We have used an e-portfolio to determine the optimal number of times the students need to repeat a procedure to be able to perform it independently. The results were compared with the actual performance during the internships. An e-portfolio collected qualitative information about the internships. Quantitative information was also requested about the number of times each clinical skill was performed. Later, a survey asked these students and their teachers the optimal number of times each skill should be repeated before it could be considered fully acquired. The questionnaire was answered by 98.6% of the students and 70.3% of their teachers. Out of the 21 clinical skills and procedures selected, both students and their tutors agreed in a similar optimal value in 16 of them; only in five of them, teachers thought that students needed a greater number of times than that selected by the students. When these optimal values were compared with the actual values recorded in the portfolio during the internships, it was found that about half of the clinical skills were carried out less frequently than expected, thus providing an important feedback about the internships. Quantitative information collected in portfolios reveals a moderate mismatch between students and tutors perceptions of their training needs.

Background: Kawasaki disease (KD) is a form of vasculitis that primarily affects children under the age of 5 years old. Patients may be missed diagnosis when initial clinical symptoms do not fulfill the traditional criteria. We aimed to analyze factors that clinicians could use to differentiate febrile children suspected of KD. Method: We retrospectively enrolled a total of 83 febrile children who were initially suspected of KD, but they did not meet the American Heart Association (AHA) criteria for a diagnosis. However, some of these patients were diagnosed with KD during their second visit. We analyzed patients' characteristics, clinical symptoms, and laboratory data. Results: In total, 50 patients were enrolled in the study. Of those, ten patients were diagnosed with KD on their second visit (group 1), while the other 40 patients still did not fit a KD diagnosis (group 2). A patient with a neutrophil to lymphocyte ratio greater than 1.33 combined with a C-reactive protein more than 33 mg/L was more likely to have KD. Conclusion: Among patients suspected of KD that did not initially meet the criteria, clinicians should pay special attention to elevated neutrophil-to-lymphocyte ratios and CRP levels and closely follow up such patients.

The morbidity and mortality caused by invasive fungal infections is increasing across the globe due to developments in transplant surgery, the use of immunosuppressive agents, and the emergence of drug-resistant fungal strains, which has led to a challenge in terms of treatment due to the limitations of three classes of drugs. Hence, it is imperative to establish effective strategies to identify and design new antifungal drugs. Drug repurposing is an effective way of expanding the application of existing drugs. In the last years, various existing drugs have been shown to be useful in the prevention and treatment of the invasive fungi. In this review, we summarize the currently used antifungal agents. In addition, the most up to date information on the effectiveness of existing drugs with antifungal activity is discussed. Moreover, the antifungal mechanisms of existing drugs are highlighted. These data will provide valuable knowledge to stimulate further investigation and clinical application in this field.

The rise in prevalence of obesity in women of reproductive age in both developed and developing countries might propagate intergenerational cycles of detrimental effects on metabolic health, contributing to substantial economic burden on society. Placental lipid metabolism might be disrupted by maternal obesity, which possibly affects the life-long health of the offspring. Here, we investigated placental lipid metabolism and handling from women with pre-gestational obesity as a sole pregnancy complication and compared to placental responses of lean women. Open profile and targeted lipidomics were used to assess placental lipids and oxidized products of docosahexahenoic acid (DHA), neuroprostanes, and arachidonic acid (AA), isoprostanes. Placental fatty acid transporters FABP1, FABP3 and endothelial lipase protein were measured. Despite no signs of overall alterations in lipid content, increased contents of DHA, AA, DHA-derived neuroprostanes and AA-derived isoprostanes and decreased content of FABP1 protein were found in placentas from obese women. Multivariate analyses suggested that these oxidised fatty acids are associated with maternal and placental inflammation and also with birth weight. These results might shed light on the molecular mechanisms associated with altered fatty acid metabolism and lipid handling in maternal pre-gestational obesity, placing these oxidized fatty acids as novel mediators of placental function.

The Visible Infrared Imaging Radiometer Suite (VIIRS) on-board the second Joint Polar Satellite System (JPSS) completed its sensor level testing in February 2018. The JPSS-2 (J2) mission is scheduled to launch in 2022, and will be very similar to its two predecessor missions, the Suomi National Polar-orbiting Partnership (SNPP) mission, launched on 28 October 2011, and JPSS-1 (renamed NOAA-20) launched on 18 November 2017. VIIRS instrument has 22 spectral bands covering the spectrum between 0.4 and 12.6 mircron: 14 reflective solar bands (RSB), 7 thermal emissive bands (TEB), and one day-night band (DNB). It is a cross-track scanning radiometer capable of providing global measurements through observations at two spatial resolutions, 375 m and 750 m at nadir for the imaging bands and moderate bands, respectively. This paper will provide an overview of J2 VIIRS characterization methodologies and calibration performance during the pre-launch testing phases performed by the National Aeronautics and Space Administration (NASA) VIIRS Characterization Support Team (VCST) to evaluate the at-launch baseline radiometric performance and generate the parameters needed to populate the sensor data record (SDR) Look-Up-Tables (LUTs). Key sensor performance metrics include the signal to noise ratio (SNR), radiance dynamic range, reflective and emissive bands calibration performance, polarization sensitivity, spectral performance, response versus scan-angle (RVS), and scattered light response. A set of performance metrics generated during the pre-launch testing program will be compared to both the SNPP and JPSS-1 VIIRS sensors.

Chikungunya is a mosquito-borne viral disease caused by Chikungunya virus (CHIKV. We conducted this study determine the seroprevalence and clinical presentation of Chikungunya infection among outpatients seeking healthcare in Mzuzu City, Malawi. Blood samples were collected from malaria negative and non-septic febrile outpatients with fevers ≥38 °C, for not more than 5 days. The enzyme- linked immunosorbent assay (ELISA) test was used to detect anti-CHIKV IgM antibodies and its results were used to determine seroprevalence of Chikungunya. A total of 119 serum samples were tested, of these, 73 (61.3%) tested positive for anti-CHIKV IgM antibodies by ELISA. Laboratory requisition forms were used to capture demographic information such as age, sex, clinical signs and symptoms presented by the enrolled patients. Age groups of 1-9, 10- 19, 20- 29, 30- 39, 40- 49, and ≥50 years had 17.8% (n= 13), 12.3 %,( n=9), 15.1%) (n=11), 19.2%; (n=14), 17.8% (n=13) and 17.8% (n=13) proportion of seroprevalence respectively. Most of the CHIKV infected individuals presented with fever (52.05%), joint pain (45.21%) and abdominal pain (42.67%). The presence of anti- CHIKV IgM antibodies suggest the presence of recent CHIKV infection and therefore accurate laboratory assays are highly recommended for CHIKV diagnosis and appropriate management of febrile patients.

Background. Specific clinical risk factors that may be associated with ambulatory outcome following thrombolysis therapy in ischemic stroke patients with pre-stroke depression is not fully understood. This was investigated. Methods. Multivariate analyses were performed to identify predictors of functional ambulatory outcomes. Patient demographics and clinical risk factors served as predictive variables, while improvement or no improvement in ambulatory outcome was considered as the primary outcome. Results. A total of 595 of these patients received rtPA of which 310 patients presented with pre-stroke depression, 217 had no improvement in functional outcome, while 93 patients presented with an improvement in functional outcome. Carotid artery stenosis (OR= 11.577, 95% CI, 1.281 – 104.636, P=0.029) and peripheral vascular disease (OR= 18.040, 95% CI, 2.956-110.086, P=0.002) were more likely to be associated with an improvement in ambulation. Antihypertensive medications (OR= 7.810, 95% CI, 1.401 –43.529, P=0.019),previous TIA (OR= 0.444, 95% CI, 0.517 –0.971, P=0.012), and congestive heart failure (OR= 0.217, 95% CI, 0.318 –0.402, P=0.030) were associated with a no improvement in ambulation. Conclusion. After adjustment for covariates, more clinical risk factors were associated with no improvement when compared with improvement in functional outcome following thrombolysis therapy in an acute ischemic stroke population with pre-stroke depression.

The Swiss Personalized Health Network (SPHN) is a Swiss research infrastructure initiative that aims to facilitate the exchange of health-related data in a FAIR manner. The SPHN Dataset and SPHN RDF Schema form an essential part of the SPHN Semantic Interoperability Framework, which currently covers mostly clinical routine data. To facilitate the integration of omics data produced by the SPHN National Data Streams, a genomics extension was developed. This was done in close collaboration with clinicians, researchers, bioinformaticians, and data managers, from Swiss university hospitals, academic research groups and the omics platforms. Here, we present the genomics extension of the SPHN RDF Schema, which can be used to semantically describe genomics experiments and covers both clinical and research domains. The schema centers around the general omics process flow, with concepts that denote the individual steps, such as sample processing, assay, and data processing. Genomics-specific specializations are provided, such as library preparation, sequencing assay, and sequencing analysis. The schema also facilitates in capturing other important omics metadata, such as information about the sequencing instrument, standard operating procedure, and quality control metrics. The extension aligns with existing semantic data models and reuses common biomedical vocabularies, such as EDAM, OBI and FAIR genomes, as value sets, thereby facilitating semantic interoperability. It will be used to FAIRify data that is produced within the Swiss network and to facilitate sharing this data as one knowledge graph for reuse among its participants.

Addressing factors modulating COVID-19 is crucial since abundant clinical evidence shows that outcomes are markedly heterogeneous between patients. This requires identifying the factors and understanding how they mechanistically influence COVID-19. Here, we describe how eleven selected factors influence COVID-19 by applying the Adverse Outcome Pathway (AOP) framework well-established in regulatory toxicology. This framework aims to model the sequence of events starting from an initial interaction of a stressor with the organism and the progress through key biological events leading to an adverse health outcome. Several linear AOPs depicting pathways from the binding of the virus to ACE2 up to clinical outcomes observed in COVID-19 patients have been developed and integrated into a network offering a unique overview of the mechanisms underlying the disease. As SARS-CoV-2 infectibility and ACE2 activity are the major starting points and inflammatory response is central in the development of COVID-19, we evaluated how eleven intrinsic and extrinsic factors modulate those processes impacting clinical outcomes. Applying this AOP-aligned approach enables the identification of current knowledge gaps orientating for further research and allows to propose biomarkers to identify of high-risk patients. This approach also facilitates expertise synergy from different disciplines to address public health issues.

Background: The treatment plan of prosthetic restorations supported by dental implants require comprehensive scientific knowledge to deliver prostheses with good prognosis, even before the implant insertion. This review aims to analyze the main prosthetic determinants of the prognosis of implant-supported prostheses. Methods: A systematic review of the literature was conducted with a PICO question: "For partially or complete edentulous subjects treated with implant-supported prostheses, which prosthetic factors could affect clinical outcomes?". A literature search was performed electronically in PubMed (MEDLINE), Scopus and Cochrane Library with the following equation [PROGNOS* OR RISK] FACTOR IMPLANT DENTAL, and by hand search in relevant journals and throughout the selected papers. Results: This revision was carried out based on 50 papers focused on several prosthodontics-related risk factors that were grouped as follows: implant-connection, loading protocol, transmucosal abutments, prosthetic fit, provisionalization, type of retention, impression technique, fabrication technique, and occlusion. More than a half of the studies were systematic reviews (30%), meta-analysis (16%) or prospective evaluations of prosthesis with various kinds of events (18%). But also narrative reviews of literature (14%) and in vitro/animal studies (16%) were found. Conclusions: The current literature provides insufficient evidence for most of the investigated topics. However, based on the accumulated data, it seems reasonable to defend that the best treatment approach is the use of morse taper implants with transmucosal abutments, recorded by means of rigidly splinted copings through the pick-up technique, and screwed by milled prosthesis occlusally adjusted to minimize functional overloading.

The ability to replicate scientific experiments is a cornerstone of the scientific method. Sharing ideas, workflows, data, and protocols facilitates testing the generalizability of results, increases the speed that science progresses, and enhances quality control of published work. Fields of science such as medicine, the social sciences, and the physical sciences have embraced practices designed to increase replicability. Granting agencies, for example, may require data management plans and journals may require data and code availability statements along with the deposition of data and code in publicly available repositories. While many tools commonly used in replicable workflows such as distributed version control systems (e.g. “git”) or scripted programming languages for data cleaning and analysis may have a steep learning curve, their adoption can increase individual efficiency and facilitate collaborations both within entomology and across disciplines. The open science movement is developing within the discipline of entomology, but practitioners of these concepts or those desiring to work more collaboratively across disciplines may be unsure where or how to embrace these initiatives. This article is meant to introduce some of the tools entomologists can incorporate into their workflows to increase the replicability and openness of their work. We describe these tools and others, recommend additional resources for learning more about these tools, and discuss the benefits to both individuals and the scientific community and potential drawbacks associated with implementing a replicable workflow.

Enhance®Fitness (EF) is an evidence-based exercise program recommended for management of osteoarthritis (OA). However, access to EF is limited in rural areas. Accordingly, we evaluated the feasibility and acceptability of remotely delivered EF in rural, community-dwelling older adults with symptomatic knee OA. A single arm pilot trial of remotely delivered EF classes was conducted. Videoconferencing was used to livestream the instructor-led, 1-hour EF classes 3 days/week for 12 weeks. Outcomes were assessed at baseline and immediately post-intervention. A total of 15 participants were enrolled with a median age of 70 years (interquartile range [IQR]: 67-75) and 14 (93%) were women. Median EF class attendance rate was 91% (IQR: 85-94%). Knee pain, as measured by the Knee injury and Osteoarthritis Outcome Score (KOOS), improved significantly from baseline to 12-week endpoint (mean difference=-11.4 [95% CI:-20.9, -2.0); P=0.02). In addition, participants’ self-reported knee function improved significantly (mean difference in KOOS Function score=-11.8 [95% CI:-18.4, -5.2]; P&lt;0.01) as well as their physical capacity (mean difference in Timed Up and Go test time=1.8 seconds [95% CI: 0.2, 3.4]; P=0.03). All participants (100%) were very satisfied with remotely delivered EF classes and there were no serious adverse events. Findings from this pilot trial indicate that remotely delivered EF is feasible and acceptable in rural older adults with knee OA.

The urgency to develop vaccines against Covid-19 is putting pressure on the long and expensive development timelines which are normally required for development of lifesaving vaccines. There is a unique opportunity to take advantage of new technologies, smart and flexible design of clinical trials, and evolving regulatory science to speed up vaccine development against Covid-19 and transform vaccine development altogether.