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Introduction The COVID-19 pandemic resulted in quarantine/lockdown measures in most countries. Quarantine may create intense psychological problems including post-traumatic stress disorder (PTSD) especially for the vulnerable critically developing children/adolescents. Few studies evaluated PTSD associated with infectious disasters but no Saudi study investigated PTSD associated with COVID-19 in children/adolescents. This study was undertaken to screen for PTSD in children/adolescent in Saudi Arabia to identify its prevalence/risk factors during COVID-19 pandemic and its quarantine. Methods A cross-sectional survey was conducted after 2 months form start of quarantine for COVID-19 pandemic utilizing the original English version and an Arabic translated version for the University of California at Los Angeles Brief COVID-19 Screen for Child/Adolescent PTSD that can be parent-reported or self-completed by older children/adolescents. Participants (Saudi citizens/non-Saudi residents) were approached online via social media. Results Five hundred and thirty seven participants were enrolled. The participants were 262 boys and 275 girls with a mean age of 12.25±3.77 years. Symptoms of no, minimal, mild and potential PTSD were identified in 15.5%, 44.1%, 27.4% and 13.0% of children/adolescents, respectively. The age, gender, school grade, and residence were not predictive of PTSD symptoms. Univariate analysis of risk factors for PTSD revealed that work of a close relative around people who might be infected was significantly different between groups of PTSD symptoms, but this difference disappeared during multivariate analysis. Children/adolescents of Saudi citizens had significantly lower median total PTSD score than children/adolescents of expatriate families (p = 0.002). Conclusion PTSD associated with the COVID-19 and its resultant quarantine shouldn’t be overlooked in different populations as it is expected in a considerable proportion of children/adolescents with variable prevalence, risk factors and severity. Parents/healthcare providers must be aware of PTSD associated with COVID-19 or similar disasters, so, they can provide children/adolescent with effective coping mechanisms.

Genomics and genome screening are proving central to the study of cancer. However, a good appreciation of the protein structures coded by cancer genes is also invaluable, especially for the understanding of functions, for assessing ligandability of potential targets, and for designing new drugs. To complement the wealth of information on the genetics of cancer in COSMIC, the most comprehensive database for cancer somatic mutations available, structural information obtained experimentally has been brought together recently in COSMIC-3D. Even where structural information is available for a gene in the Cancer Gene Census, a list of genes in COSMIC with substantial evidence supporting their impacts in cancer, this information is quite often for a single domain in a larger protein or for a single protomer in a multiprotein assembly. Here, we show that over 60% of the genes included in the Cancer Gene Census are predicted to possess multiple domains. Many are also multicomponent and membrane-associated molecular assemblies, with mutations recorded in COSMIC affecting such assemblies. However, only 469 of the gene products have a structure represented in the PDB, and of these only 87 structures have 90-100% coverage over the sequence and 69 have less than 10% coverage. As a first step to bridging gaps in our knowledge in the many cases where individual protein structures and domains are lacking, we discuss our attempts of protein structure modelling using our pipeline and investigating the effects of mutations using two of our in-house methods (SDM2 and mCSM) and identifying potential driver mutations. This allows us to begin to understand the effects of mutations not only on protein stability but also on protein-protein, protein-ligand and protein-nucleic acid interactions. In addition, we consider ways to combine the structural information with the wealth of mutation data available in COSMIC. We discuss the impacts of COSMIC missense mutations on protein structure in order to identify and assess the molecular consequences of cancer-driving mutations.

INTRODUCTION:Accelerating progress in reducing child deaths is needed in order to achieve the Sustainable Development Goal child mortality target. This will require a focus on vulnerable children-including young children, those who are undernourished or with acute illnesses requiring hospitalization. Improving adherence to inpatient guidelines may be an important strategy to reduce child mortality, including among the most vulnerable. The aim of our assessment of nine sub-Saharan African and South Asian hospitals was to determine adherence to pediatric inpatient care recommendations, in addition to capacity for and barriers to implementation of guideline-adherent care prior to commencing the Childhood Acute Illness and Nutrition (CHAIN) Cohort study. The CHAIN Cohort study aims to identify modifiable risk factors for poor inpatient and post discharge outcomes above and beyond implementation of guidelines. METHODS:Hospital infrastructure, staffing, durable equipment, and consumable supplies such as medicines and laboratory reagents, were evaluated through observation and key informant interviews. Inpatient medical records of 2-23 month old children were assessed for adherence to national and international guidelines. The records of children with severe acute malnutrition (SAM) were oversampled to reflect the CHAIN study population. Seven core adherence indicators were examined: oximetry and oxygen therapy, fluids, anemia diagnosis and transfusion, antibiotics, malaria testing and antimalarials, nutritional assessment and management, and HIV testing. RESULTS:All sites had facilities and equipment necessary to implement care consistent with World Health Organization and national guidelines. However, stockouts of essential medicines and laboratory reagents were reported to be common at some sites, even though they were mostly present during the assessment visits. Doctor and nurse to patient ratios varied widely. We reviewed the notes of 261 children with admission diagnoses of sepsis (17), malaria (47), pneumonia (70), diarrhea (106), and SAM (119); 115 had multiple diagnoses. Adherence to oxygen therapy, antimalarial, and malnutrition refeeding guidelines was >75%. Appropriate antimicrobials were prescribed for 75% of antibiotic-indicative conditions. However, 20/23 (87%) diarrhea and 20/27 (74%) malaria cases without a documented indication were prescribed antibiotics. Only 23/122 (19%) with hemoglobin levels meeting anemia criteria had recorded anemia diagnoses. HIV test results were infrequently documented even at hospitals with universal screening policies (66/173, 38%). Informants at all sites attributed inconsistent guideline implementation to inadequate staffing. CONCLUSION:Assessed hospitals had the infrastructure and equipment to implement guideline-consistent care. While fluids, appropriate antimalarials and antibiotics, and malnutrition refeeding adherence was comparable to published estimates from low- and high-resource settings, there were inconsistencies in implementation of some other recommendations. Stockouts of essential therapeutics and laboratory reagents were a noted barrier, but facility staff perceived inadequate human resources as the primary constraint to consistent guideline implementation.

Ureaplasma species are the most frequently isolated microorganisms inside the amniotic cavity and have been associated with spontaneous abortion, chorioamnionitis, premature rupture of the membranes (PROM), preterm labour (PL) pneumonia in neonates and bronchopulmonary dysplasia in neonates. The mechanisms by which Ureaplasmas cause such diseases remain unclear, but it is believed that inappropriate induction of inflammatory responses is involved, triggered by the innate immune system. As part of its mechanism of activation, the innate immune system employs germ-lined encoded receptors, called pattern recognition receptors (PRRs) in order to "sense" pathogens. One such family of PRRs are the Toll like receptor family (TLR). In the current study we aimed to elucidate the role of TLRs in Ureaplasma-induced inflammation in human amniotic epithelial cells. Using silencing, as well as human embryonic kidney (HEK) transfected cell lines, we demonstrate that TLR2, TLR6 and TLR9 are involved in the inflammatory responses against Ureaplasma parvum and urealyticum serovars. Ureaplasma lipoproteins, such as Multiple Banded antigen (MBA), trigger responses via TLR2/TLR6, whereas the whole bacterium is required for TLR9 activation. No major differences were observed between the different serovars. Cell activation by Ureaplasma parvum and urealyticum seem to require lipid raft function and formation of heterotypic receptor complexes comprising of TLR2 and TLR6 on the cell surface and TLR9 intracellularly.

[This corrects the article DOI: 10.1371/journal.pone.0061199.].

ObjectiveParkinson's disease (PD) is an age-related neurodegenerative condition characterized mostly by motor symptoms. Although a wide range of non-motor symptoms (NMS) are frequently experienced by PD patients. One of the important and common NMS is cognitive impairment, which is measured using different cognitive scales. Monitoring cognitive impairment and its decline in PD is essential for patient care and management. In this study, our goal is to identify the most effective cognitive scale in predicting cognitive decline over a 5-year timeframe initializing clinical biomarkers and DAT SPECT.MethodsMachine Learning has previously shown superior performance in image and clinical data classification and detection. In this study, we propose to use machine learning with different types of data, such as DAT SPECT and clinical biomarkers, to predict PD-CD based on various cognitive scales. We collected 330 DAT SPECT images and their clinical data in baseline, years 2,3,4, and 5 from Parkinson's Progression Markers Initiative (PPMI). We then designed a 3D Autoencoder to extract deep radiomic features (DF) from DAT SPECT images, and we then concatenated it with 17 clinical features (CF) to predict cognitive decline based on Montreal Cognitive Assessment (MoCA) and The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS-I).ResultsThe utilization of MoCA as a cognitive decline scale yielded better performance in various years compared to MDS-UPDRS-I. In year 4, the application of the deep radiomic feature resulted in the highest achievement, with a cross-validation AUC of 89.28, utilizing the gradient boosting classifier. For the MDS-UPDRS-I scale, the highest achievement was obtained by utilizing the deep radiomic feature, resulting in a cross-validation AUC of 81.34 with the random forest classifier.ConclusionsThe study findings indicate that the MoCA scale may be a more effective predictor of cognitive decline within 5 years compared to MDS-UPDRS-I. Furthermore, deep radiomic features had better performance compared to sole clinical biomarkers or clinical and deep radiomic combined. These results suggest that using the MoCA score and deep radiomic features extracted from DAT SPECT could be a promising approach for identifying individuals at risk for cognitive decline in four years. Future research is needed to validate these findings and explore their utility in clinical practice.

[This corrects the article DOI: 10.1371/journal.pone.0248511.].

BackgroundDegenerative Cervical Myelopathy (DCM) is one of the most common degenerative disorders of cervical spine and sources of cord dysfunction in adults. It usually manifests with neurologic presentations such as loss of dexterity and gait issues. Treatment for moderate and severe cases of DCM is surgical decompression of the region. There are many approaches available for surgical intervention which could be categorized into anterior and posterior based on the side of neck where operation takes place. Additionally, for certain cases the hybridized anterior-posterior combined surgery is indicated. While there are many technical differences between these approaches with each having its own advantages, the complications and safety profiles of them are not fully disclosed. This protocol aims to systematically search for current reports on complications of surgical decompression methods of DCM and pool them for robust evidence generation.MethodSearch will be carried out in PubMed, Scopus, and Cochrane databases for retrospective and prospective surgical series, cohorts, or trials being performed for DCM with at least a sample size of 20 patients. Query strings will be designed to capture reports with details of complications with no year limit. Studies not being original (e.g., review articles, case reports, etc.), not in English, having patients younger than 18-years-old, and not reporting at least one complication will be excluded. Two independent reviewers will review the titles and abstracts for first round of screening. Full text of retrieved studies from previous round will be screened again by the same reviewers. In case of discrepancy, the third senior reviewer will be consulted. Eligible studies will then be examined for data extraction where data will be recorded into standardized form. Cumulative incidence and 95% confidence intervals of complication will be then pooled based on generalized linear mixed models with consideration of approach of surgery as subgroups. Heterogeneity tests will be performed for assessment of risk of bias.DiscussionThis systematic review is aimed at providing practical information for spine surgeons on the rates of complications of different surgical approaches of DCM decompression. Proper decision-making regarding the surgical approach in addition to informing patients could be facilitated through results of this investigation.

Introduction: Accelerating progress in reducing child deaths is needed in order to achieve the Sustainable Development Goal child mortality target. This will require a focus on vulnerable children–including young children, those who are undernourished or with acute illnesses requiring hospitalization. Improving adherence to inpatient guidelines may be an important strategy to reduce child mortality, including among the most vulnerable. The aim of our assessment of nine sub-Saharan African and South Asian hospitals was to determine adherence to pediatric inpatient care recommendations, in addition to capacity for and barriers to implementation of guideline-adherent care prior to commencing the Childhood Acute Illness and Nutrition (CHAIN) Cohort study. The CHAIN Cohort study aims to identify modifiable risk factors for poor inpatient and post discharge outcomes above and beyond implementation of guidelines. Methods: Hospital infrastructure, staffing, durable equipment, and consumable supplies such as medicines and laboratory reagents, were evaluated through observation and key informant interviews. Inpatient medical records of 2–23 month old children were assessed for adherence to national and international guidelines. The records of children with severe acute malnutrition (SAM) were oversampled to reflect the CHAIN study population. Seven core adherence indicators were examined: oximetry and oxygen therapy, fluids, anemia diagnosis and transfusion, antibiotics, malaria testing and antimalarials, nutritional assessment and management, and HIV testing. Results: All sites had facilities and equipment necessary to implement care consistent with World Health Organization and national guidelines. However, stockouts of essential medicines and laboratory reagents were reported to be common at some sites, even though they were mostly present during the assessment visits. Doctor and nurse to patient ratios varied widely. We reviewed the notes of 261 children with admission diagnoses of sepsis (17), malaria (47), pneumonia (70), diarrhea (106), and SAM (119); 115 had multiple diagnoses. Adherence to oxygen therapy, antimalarial, and malnutrition refeeding guidelines was >75%. Appropriate antimicrobials were prescribed for 75% of antibiotic-indicative conditions. However, 20/23 (87%) diarrhea and 20/27 (74%) malaria cases without a documented indication were prescribed antibiotics. Only 23/122 (19%) with hemoglobin levels meeting anemia criteria had recorded anemia diagnoses. HIV test results were infrequently documented even at hospitals with universal screening policies (66/173, 38%). Informants at all sites attributed inconsistent guideline implementation to inadequate staffing. Conclusion: Assessed hospitals had the infrastructure and equipment to implement guideline-consistent care. While fluids, appropriate antimalarials and antibiotics, and malnutrition refeeding adherence was comparable to published estimates from low- and high-resource settings, there were inconsistencies in implementation of some other recommendations. Stockouts of essential therapeutics and laboratory reagents were a noted barrier, but facility staff perceived inadequate human resources as the primary constraint to consistent guideline implementation. [ABSTRACT FROM AUTHOR]

BackgroundPolypharmacy can be a consequence of overprescribing that is prevalent in older adults with multimorbidity. Polypharmacy can cause adverse reactions and result in hospital admission. This study predicted risks of adverse drug reaction (ADR)-related and emergency hospital admissions by medicine classes.MethodsWe used electronic health record data from general practices of Clinical Practice Research Datalink (CPRD GOLD) and Aurum. Older patients who received at least five medicines were included. Medicines were classified using the British National Formulary sections. Hospital admission cases were propensity-matched to controls by age, sex, and propensity for specific diseases. The matched data were used to develop and validate random forest (RF) models to predict the risk of ADR-related and emergency hospital admissions. Shapley Additive eXplanation (SHAP) values were calculated to explain the predictions.ResultsIn total, 89,235 cases with polypharmacy and hospitalised with an ADR-related admission were matched to 443,497 controls. There were over 112,000 different combinations of the 50 medicine classes most implicated in ADR-related hospital admission in the RF models, with the most important medicine classes being loop diuretics, domperidone and/or metoclopramide, medicines for iron-deficiency anaemias and for hypoplastic/haemolytic/renal anaemias, and sulfonamides and/or trimethoprim. The RF models strongly predicted risks of ADR-related and emergency hospital admission. The observed Odds Ratio in the highest RF decile was 7.16 (95% CI 6.65-7.72) in the validation dataset. The C-statistics for ADR-related hospital admissions were 0.58 for age and sex and 0.66 for RF probabilities.ConclusionsPolypharmacy involves a very large number of different combinations of medicines, with substantial differences in risks of ADR-related and emergency hospital admissions. Although the medicines may not be causally related to increased risks, RF model predictions may be useful in prioritising medication reviews. Simple tools based on few medicine classes may not be effective in identifying high risk patients.

In December 2020, UNAIDS released a new set of ambitious targets calling for 95% of all people living with HIV to know their HIV status, 95% of all people with diagnosed HIV infection to receive sustained antiretroviral therapy, and 95% of all people receiving antiretroviral therapy to have viral suppression by 2025. Adopted by United Nations Member states in June 2021 as part of the new Political Declaration on HIV and AIDS, these targets, combined with ambitious primary prevention targets and focused attention to supporting enablers, aim to bridge inequalities in treatment coverage and outcomes and accelerate HIV incidence reductions by focusing on progress in all sub-populations, age groups and geographic settings. Here we summarise the evidence and decisions underpinning the new global targets.

With the rapid progress made in the development of vaccines to fight the SARS-CoV-2 pandemic, almost >90% of vaccine candidates under development and a 100% of the licensed vaccines are delivered intramuscularly (IM). While these vaccines are highly efficacious against COVID-19 disease, their efficacy against SARS-CoV-2 infection of upper respiratory tract and transmission is at best temporary. Development of safe and efficacious vaccines that are able to induce robust mucosal and systemic immune responses are needed to control new variants. In this study, we have used our nanoemulsion adjuvant (NE01) to intranasally (IN) deliver stabilized spike protein (S-2P) to induce immunogenicity in mouse and hamster models. Data presented demonstrate the induction of robust immunity in mice resulting in 100% seroconversion and protection against SARS-CoV-2 in a hamster challenge model. There was a significant induction of mucosal immune responses as demonstrated by IgA- and IgG-producing memory B cells in the lungs of animals that received intranasal immunizations compared to an alum adjuvanted intramuscular vaccine. The efficacy of the S-2P/NE01 vaccine was also demonstrated in an intranasal hamster challenge model with SARS-CoV-2 and conferred significant protection against weight loss, lung pathology, and viral clearance from both upper and lower respiratory tract. Our findings demonstrate that intranasal NE01-adjuvanted vaccine promotes protective immunity against SARS-CoV-2 infection and disease through activation of three arms of immune system: humoral, cellular, and mucosal, suggesting that an intranasal SARS-CoV-2 vaccine may play a role in addressing a unique public health problem and unmet medical need.

BackgroundVery few previous studies have involved school students or their parents in the evaluation of virtual learning environment (VLE). Thus, this survey was performed to evaluate the satisfaction of both school students and their parents with the VLE in the Kingdom of Saudi Arabia during the COVID-19 pandemic.MethodsA cross-sectional questionnaire-based survey was distributed online for VLE evaluation. The questionnaire was based on previous studies and expert opinions from validated instruments for assessing distance education, integrative and literature reviews of VLE environment. A median value >3 indicated participant satisfaction in each of the 5 domains of the questionnaire as well as overall VLE satisfaction. The used questionnaire was checked after its implementation by all possible statistical means and it was found to be of acceptable validity and reliability.ResultsSix hundred and ninety-three participants including 571 Saudi citizens and 122 non-Saudi residents participated in this survey. The number of school students who agreed or strongly agreed were significantly lower than the number of students who disagreed or strongly disagreed with preferring the VLE over traditional education (pConclusionsThis is one of few available adequate population-based studies for exploring the VLE satisfaction of both Saudi citizens and non-Saudi residents school students and their parents. This study showed the participants' unsatisfactory VLE experience. The VLE is accepted as an alternative to traditional classrooms to keep up with learning and to maintain the safety of children and it can be a supplementary learning method but many measures are still needed to develop the VLE.

Background Schizophrenia and especially deficit schizophrenia (DSCZ) are characterized by increased activity of neuroimmunotoxic pathways and a generalized cognitive decline (G-CoDe). There is no data on whether the interleukin (IL)-6/IL-23/T helper 17 (IL-6/IL-23/Th17)-axis is more associated with DSCZ than with non-deficit schizophrenia (NDSCZ) and whether changes in this axis are associated with the G-CoDe and the phenome (a factor extracted from all symptom domains) of schizophrenia. Methods This study included 45 DSCZ and 45 NDSCZ patients and 40 controls and delineated whether the IL-6/IL-23/Th17 axis, trace elements (copper, zinc) and ions (magnesium, calcium) are associated with DSCZ, the G-CoDe and the schizophrenia phenome. Results Increased plasma IL-23 and IL-6 levels were associated with Th17 upregulation, assessed as a latent vector (LV) extracted from IL-17, IL-21, IL-22, and TNF-α. The IL-6/IL-23/Th17-axis score, as assessed by an LV extracted from IL-23, IL-6, and the Th17 LV, was significantly higher in DSCZ than in NDSCZ and controls. We discovered that 70.7% of the variance in the phenome was explained by the IL-6/IL-23/Th17-axis (positively) and the G-CoDe and IL-10 (both inversely); and that 54.6% of the variance in the G-CoDe was explained by the IL-6/IL-23/Th17 scores (inversely) and magnesium, copper, calcium, and zinc (all positively). Conclusion The pathogenic IL-6/IL-23/Th17-axis contributes to the generalized neurocognitive deficit and the phenome of schizophrenia, especially that of DSCZ, due to its key role in peripheral inflammation and neuroinflammation and its consequent immunotoxic effects on neuronal circuits. These clinical impairments are more prominent in subjects with lowered IL-10, magnesium, calcium, and zinc.

Since chlorpyrifos (CPF), a major organophosphorus pesticide, is widely used for agricultural and domestic purposes, thus, humans may be exposed to these toxic compounds through multiple sources. In recent years, significant concerns have been raised regarding the deleterious effects of exposure to CPF on human health, especially growing fetus. Therefore, in this study, we aimed to evaluate the health risks of exposure to CPF among pregnant women living in Isfahan province, Iran, using deterministic and probabilistic approaches. The urinary concentration of 3, 5, 6-trichloro-2-pyridinol (TCP), the most common metabolite of CPF, was measured as the biomarker of current exposure to CPF. For this purpose, spot urine samples were taken from 110 pregnant women and the urinary concentrations of TCP were quantified. The estimated daily intake and hazard quotient (HQ) for CPF exposure were measured according to the reference values set by World Health Organization (WHO) and United States Environmental Protection Agency (US EPA) for acute and chronic exposure to CPF. Based on the results, TCP was detected in more than 70% of samples (3.8 ± 2.72 μg/L). The estimated daily intake for some participants was found to be higher than the suggested reference dose by USEPA for chronic exposure to CPF. Furthermore, the HQ>1 was obtained for 20% of the study population in Monte-Carlo analysis using USEPA chronic reference dose, indicating that chronic toxic effects are expected at least for a part of the target population. Based on the findings, proper measures should be taken to reduce the exposure of Iranian pregnant women to CPF and resultant health risks.

Industrialization plays a vital role in the development of a country’s economy. However, it also adversely affects the environment by discharging various unwanted and harmful substances such as heavy metals into the surface and subsurface aquifers. The current research work investigates the identification, characterization, and evaluation of specific heavy metals in industrial wastewater (IWW) and different composite samples of soil and vegetables (onion, pumpkin, lady finger, and green pepper) collected from selected agricultural fields irrigated with canals fed IWW in Mingora city of Swat (Pakistan). Obtained results were compared with the tube well water irrigated soil and vegetables grown in it. Heavy metals accumulation was tested through wet digestion method and atomic absorption spectrophotometry (AAS). The metal transfer factor (MTF) of heavy metals from soil to vegetables was also determined along with the health index (HI) to assess the potential health risk of the metals towards consumers using Monte Carlo simulation technique. Analysis of water samples showed that the concentration in mg l-1 of heavy metals in IWW follows the trend Fe (6.72) > Cr (0.537) > Pb (0.393) > Co (0.204) > Mn (0.125) > Ni (0.121). Analysis of the soil samples irrigated with IWW followed the order of Fe (47.27) > Pb (2.92) > Cr (2.90) >Ni (1.02) > Mn (0.90) > Co (0.68) and Fe (17.12) > Pb (2.12) > Cr (2.03) >Ni (0.76) > Co (0.49) > Mn (0.23) irrigated with TWW. Heavy metals concentration values found in soil irrigated with IWW were higher than the soil irrigated with TWW. Similar trends were found for agricultural produces grown on soil irrigated with IWW and found higher than the normal allowable WHO limits, indicating higher possibilities of health risks if continuously consumed. MTF values were found higher than 1 for ladyfinger and green pepper for Pb intake and pumpkin for Mn intake. The current study suggests the continuous monitoring of soil, irrigation water and agricultural products to prevent heavy metals concentration beyond allowable limits, in the food chain. Thus, concrete preventive measures must be taken to reduce heavy metal accumulation through wastewater irrigation to protect both human and animal health in the study area of Mingora Swat Pakistan.

PurposeAvailable but insufficient evidence shows that changes may occur in the immune system following coronavirus disease 2019 (COVID-19). The present study aimed at evaluating immunological changes in patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pneumonia compared with the control group.MethodThe present study was performed on 95 patients with COVID-19 (32 severe and 63 moderate cases) and 22 healthy controls. Relationship between immune cells, disease severity and lung involvement was assessed. Binary logistic regression and ROC curve tests were used for statistical analysis.ResultsA significant decrease was observed in CD20+ cell counts of the patients. To differentiate patients from healthy individuals, the cutoff point for the CD4+ cell count was 688 /μL, sensitivity 0.96, and specificity 0.84. An increase in CD4+ cells reduces the odds of severe disease (odds ratio = 0.82, P = 0.047) and death (odds ratio = 0.74, P = 0.029). CD4+ cells play a pivotal role in the severity of lung involvement (P = 0.03). In addition to CD4+ cells, Fc gamma receptor III (FcγRIII) (CD16) also played a significant prognosis (odds ratio = 0.55, P = 0.047). In severe cases, C-reactive protein, Blood urea nitrogen, and Creatine phosphokinase levels, as well as neutrophil counts, were significantly higher than those of moderate ones whereas lymphocyte count in severe cases was lower than that of moderate ones.ConclusionThe number of total T-cells and B-cells in patients with COVID-19 was lower than that of controls; however, their NK cells increased. FcγRIII and CD4+ cells are of great importance due to their association with COVID-19 prognosis.

The restrictive measures implemented in response to the COVID-19 pandemic have triggered sudden massive changes to travel behaviors of people all around the world. This study examines the individual mobility patterns for all transport modes (walk, bicycle, motorcycle, car driven alone, car driven in company, bus, subway, tram, train, airplane) before and during the restrictions adopted in ten countries on six continents: Australia, Brazil, China, Ghana, India, Iran, Italy, Norway, South Africa and the United States. This cross-country study also aims at understanding the predictors of protective behaviors related to the transport sector and COVID-19. Findings hinge upon an online survey conducted in May 2020 (N = 9,394). The empirical results quantify tremendous disruptions for both commuting and non-commuting travels, highlighting substantial reductions in the frequency of all types of trips and use of all modes. In terms of potential virus spread, airplanes and buses are perceived to be the riskiest transport modes, while avoidance of public transport is consistently found across the countries. According to the Protection Motivation Theory, the study sheds new light on the fact that two indicators, namely income inequality, expressed as Gini index, and the reported number of deaths due to COVID-19 per 100,000 inhabitants, aggravate respondents' perceptions. This research indicates that socio-economic inequality and morbidity are not only related to actual health risks, as well documented in the relevant literature, but also to the perceived risks. These findings document the global impact of the COVID-19 crisis as well as provide guidance for transportation practitioners in developing future strategies.

Common spatial pattern (CSP) is shown to be an effective pre-processing algorithm in order to discriminate different classes of motor-based EEG signals by obtaining suitable spatial filters. The performance of these filters can be improved by regularized CSP, in which available prior information is added in terms of regularization terms into the objective function of conventional CSP. Variety of prior information can be used in this way. In this paper, we used time correlation between different classes of EEG signal as the prior information, which is clarified similarity between different classes of signal for regularizing CSP. Furthermore, the proposed objective function can be easily extended to more than two-class problems. We used three different standard datasets to evaluate the performance of the proposed method. Correlation-based CSP (CCSP) outperformed original CSP as well as the existing regularized CSP, Principle Component Cnalysis (PCA) and Fisher Discriminate Analysis (FDA) in both two-class and multi-class scenarios. The simulation results showed that the proposed method outperformed conventional CSP by 6.9% in 2-class and 2.23% in multi-class problem in term of mean classification accuracy.

ObjectivesTo determine clinical, laboratory features and outcomes of Multisystem Inflammatory Syndrome in children (MIS-C) and its comparison with historic Kawasaki Disease (KD) and Viral Myocarditis (VM) cohorts.MethodsAll children (1 month- 18 years) who fulfilled the World Health Organization criteria of MIS-C presenting to two tertiary care centers in Karachi from May 2020 till August 31st were included. KD and VM admitted to one of the study centers in the last five years prior to this pandemic, was compared to MIS-C.ResultsThirty children with median age of 24 (interquartile range (IQR)1-192) months met the criteria for MIS-C. Three phenotypes were identified, 12 patients (40%) with KD, ten (33%) VM and eight (26%) had features of TSS. Echocardiography showed coronary involvement in 10 (33%), and moderate to severe Left Ventricular dysfunction in 10 (33%) patients. Steroids and intravenous immunoglobulins (IVIG) were administered to 24 (80%) and 12 (41%) patients respectively while 7 (23%) received both. Overall, 20% children expired. During the last five years, 30 and 47 children were diagnosed with KD and VM, respectively. Their comparison with MIS-C group showed lymphopenia, thrombocytosis, and higher CRP as well as more frequent atypical presentation in MIS-C KD group with less coronary involvement. The MIS-C VM was more likely to present with fulminant myocarditis.ConclusionsOur MIS-C cohort is younger with higher mortality compared to previous reports. MIS-C is distinct from historic cohorts of KD and VM in both in clinical features and outcomes.

Ureaplasma species are the most frequently isolated microorganisms inside the amniotic cavity and have been associated with spontaneous abortion, chorioamnionitis, premature rupture of the membranes (PROM), preterm labour (PL) pneumonia in neonates and bronchopulmonary dysplasia in neonates. The mechanisms by which Ureaplasmas cause such diseases remain unclear, but it is believed that inappropriate induction of inflammatory responses is involved, triggered by the innate immune system. As part of its mechanism of activation, the innate immune system employs germ-lined encoded receptors, called pattern recognition receptors (PRRs) in order to “sense” pathogens. One such family of PRRs are the Toll like receptor family (TLR). In the current study we aimed to elucidate the role of TLRs in Ureaplasma-induced inflammation in human amniotic epithelial cells. Using silencing, as well as human embryonic kidney (HEK) transfected cell lines, we demonstrate that TLR2, TLR6 and TLR9 are involved in the inflammatory responses against Ureaplasma parvum and urealyticum serovars. Ureaplasma lipoproteins, such as Multiple Banded antigen (MBA), trigger responses via TLR2/TLR6, whereas the whole bacterium is required for TLR9 activation. No major differences were observed between the different serovars. Cell activation by Ureaplasma parvum and urealyticum seem to require lipid raft function and formation of heterotypic receptor complexes comprising of TLR2 and TLR6 on the cell surface and TLR9 intracellularly. [ABSTRACT FROM AUTHOR]

Many sets of human facial photographs produced in Western cultures are available for scientific research. We report here on the development of a face database of Turkish undergraduate student targets. High-resolution standardized photographs were taken and supported by the following materials: (a) basic demographic and appearance-related information, (b) two types of landmark configurations (for Webmorph and geometric morphometrics (GM)), (c) facial width-to-height ratio (fWHR) measurement, (d) information on photography parameters, (e) perceptual norms provided by raters. We also provide various analyses and visualizations of facial variation based on rating norms using GM. Finally, we found that there is sexual dimorphism in fWHR in our sample but that this is accounted for by body mass index. We present the pattern of associations between rating norms, GM and fWHR measurements. The database and supporting materials are freely available for scientific research purposes.

Unpredictable forces which perturb balance are frequently applied to the body through interaction between the upper limb and the environment. Lower limb muscles respond rapidly to these postural disturbances in a highly specific manner. We have shown that the muscle activation patterns of lower limb muscles are organized in a direction specific manner which changes with lower limb stability. Ankle muscles change their activity within 80 ms of the onset of a force perturbation applied to the hand which is earlier than the onset of changes in ground reaction force, ankle angle or head motion. The latency of the response is sensitive to the perturbation direction. However, neither the latency nor the magnitude of the response is affected by stiffening the arm even though this alters the magnitude and timing of motion of the body segments. Based on the short latency, insensitivity of the change in ankle muscle activation to motion of the body segments but sensitivity to perturbation direction we reason that changes in ankle muscle activation are most likely triggered by sensory signals originating from cutaneous receptors in the hand. Furthermore, evidence that the latency of changes in ankle muscle activation depends on the number of perturbation directions suggests that the neural pathway is not confined to the spinal cord.

BACKGROUND:Decreased hepatitis C virus (HCV) clearance, faster cirrhosis progression and higher HCV RNA levels are associated with Human Immunodeficiency virus (HIV) coinfection. The CD4+ T helper cytokines interleukin (IL)-21 and IL-17A are associated with virus control and inflammation, respectively, both important in HCV and HIV disease progression. Here, we examined how antigen-specific production of these cytokines during HCV mono and HIV/HCV coinfection was associated with HCV virus control. METHODS:We measured HCV-specific IL-21 and IL-17A production by transwell cytokine secretion assay in PBMCs from monoinfected and coinfected individuals. Viral control was determined by plasma HCV RNA levels. RESULTS:In acutely infected individuals, those able to establish transient/complete HCV viral control tended to have stronger HCV-specific IL-21-production than non-controllers. HCV-specific IL-21 production also correlated with HCV viral decline in acute infection. Significantly stronger HCV-specific IL-21 production was detected in HAART-treated coinfected individuals. HCV-specific IL-17A production was not associated with lower plasma HCV RNA levels in acute or chronic HCV infection and responses were stronger in HIV coinfection. HCV-specific IL-21/ IL-17A responses did not correlate with microbial translocation or fibrosis. Exogenous IL-21 treatment of HCV-specific CD8+ T cells from monoinfected individuals enhanced their function although CD8+ T cells from coinfected individuals were somewhat refractory to the effects of IL-21. CONCLUSIONS:These data show that HCV-specific IL-21 and IL-17A-producing T cells are induced in HIV/HCV coinfection. In early HIV/HCV coinfection, IL-21 may contribute to viral control, and may represent a novel tool to enhance acute HCV clearance in HIV/HCV coinfected individuals.

Aberrant DNA methylation is a frequent epigenetic alteration in cancer cells that has emerged as a pivotal mechanism for tumorigenesis. Accordingly, novel therapies targeting the epigenome are being explored with the aim to restore normal DNA methylation patterns on oncogenes and tumor suppressor genes. A limited number of studies indicate that dietary compound resveratrol modulates DNA methylation of several cancer-related genes; however a complete view of changes in methylome by resveratrol has not been reported yet. In this study we performed a genome-wide survey of DNA methylation signatures in triple negative breast cancer cells exposed to resveratrol. Our data showed that resveratrol treatment for 24 h and 48 h decreased gene promoter hypermethylation and increased DNA hypomethylation. Of 2476 hypermethylated genes in control cells, 1,459 and 1,547 were differentially hypomethylated after 24 h and 48 h, respectively. Remarkably, resveratrol did not induce widespread non-specific DNA hyper- or hypomethylation as changes in methylation were found in only 12.5% of 27,728 CpG loci. Moreover, resveratrol restores the hypomethylated and hypermethylated status of key tumor suppressor genes and oncogenes, respectively. Importantly, the integrative analysis of methylome and transcriptome profiles in response to resveratrol showed that methylation alterations were concordant with changes in mRNA expression. Our findings reveal for the first time the impact of resveratrol on the methylome of breast cancer cells and identify novel potential targets for epigenetic therapy. We propose that resveratrol may be considered as a dietary epidrug as it may exert its anti-tumor activities by modifying the methylation status of cancer -related genes which deserves further in vivo characterization.

In order to maintain organs and structures at their appropriate sizes, multicellular organisms orchestrate cell proliferation and post-mitotic cell expansion during morphogenesis. Recent studies using Arabidopsis leaves have shown that compensation, which is defined as post-mitotic cell expansion induced by a decrease in the number of cells during lateral organ development, is one example of such orchestration. Some of the basic molecular mechanisms underlying compensation have been revealed by genetic and chimeric analyses. However, to date, compensation had been observed only in mutants, transgenics, and γ-ray-treated plants, and it was unclear whether it occurs in plants under natural conditions. Here, we illustrate that a shift in ambient temperature could induce compensation in Rorippa aquatica (Brassicaceae), a semi-aquatic plant found in North America. The results suggest that compensation is a universal phenomenon among angiosperms and that the mechanism underlying compensation is shared, in part, between Arabidopsis and R. aquatica.

A main challenge of data-driven sciences is how to make maximal use of the progressively expanding databases of experimental datasets in order to keep research cumulative. We introduce the idea of a modeling-based dataset retrieval engine designed for relating a researcher's experimental dataset to earlier work in the field. The search is (i) data-driven to enable new findings, going beyond the state of the art of keyword searches in annotations, (ii) modeling-driven, to include both biological knowledge and insights learned from data, and (iii) scalable, as it is accomplished without building one unified grand model of all data. Assuming each dataset has been modeled beforehand, by the researchers or automatically by database managers, we apply a rapidly computable and optimizable combination model to decompose a new dataset into contributions from earlier relevant models. By using the data-driven decomposition, we identify a network of interrelated datasets from a large annotated human gene expression atlas. While tissue type and disease were major driving forces for determining relevant datasets, the found relationships were richer, and the model-based search was more accurate than the keyword search; moreover, it recovered biologically meaningful relationships that are not straightforwardly visible from annotations-for instance, between cells in different developmental stages such as thymocytes and T-cells. Data-driven links and citations matched to a large extent; the data-driven links even uncovered corrections to the publication data, as two of the most linked datasets were not highly cited and turned out to have wrong publication entries in the database.

The ARF GTPase Activating Protein 1 (ARFGAP1) associates mainly with the cytosolic side of Golgi cisternal membranes where it participates in the formation of both COPI and clathrin-coated vesicles. In this study, we show that ARFGAP1 associates transiently with lipid droplets upon addition of oleate in cultured cells. Also, that addition of cyclic AMP shifts ARFGAP1 from lipid droplets to the Golgi apparatus and that overexpression and knockdown of ARFGAP1 affect lipid droplet formation. Examination of human liver tissue reveals that ARFGAP1 is found associated with lipid droplets at steady state in some but not all hepatocytes.

The use of chemopreventive natural compounds represents a promising strategy in the search for novel therapeutic agents in cancer. Resveratrol (3,4',5-trans-trihydroxystilbilene) is a dietary polyphenol found in fruits, vegetables and medicinal plants that exhibits chemopreventive and antitumor effects. In this study, we searched for modulated proteins with preventive or therapeutic potential in MCF-7 breast cancer cells exposed to resveratrol. Using two-dimensional electrophoresis we found significant changes (FC >2.0; p≤0.05) in the expression of 16 proteins in resveratrol-treated MCF-7 cells. Six down-regulated proteins were identified by tandem mass spectrometry (ESI-MS/MS) as heat shock protein 27 (HSP27), translationally-controlled tumor protein, peroxiredoxin-6, stress-induced-phosphoprotein-1, pyridoxine-5'-phosphate oxidase-1 and hypoxanthine-guanine phosphoribosyl transferase; whereas one up-regulated protein was identified as triosephosphate isomerase. Particularly, HSP27 overexpression has been associated to apoptosis inhibition and resistance of human cancer cells to therapy. Consistently, we demonstrated that resveratrol induces apoptosis in MCF-7 cells. Apoptosis was associated with a significant increase in mitochondrial permeability transition, cytochrome c release in cytoplasm, and caspases -3 and -9 independent cell death. Then, we evaluated the chemosensitization effect of increasing concentrations of resveratrol in combination with doxorubicin anti-neoplastic agent in vitro. We found that resveratrol effectively sensitize MCF-7 cells to cytotoxic therapy. Next, we evaluated the relevance of HSP27 targeted inhibition in therapy effectiveness. Results evidenced that HSP27 inhibition using RNA interference enhances the cytotoxicity of doxorubicin. In conclusion, our data indicate that resveratrol may improve the therapeutic effects of doxorubicin in part by cell death induction. We propose that potential modulation of HSP27 levels using natural alternative agents, as resveratrol, may be an effective adjuvant in breast cancer therapy.

Viral vectors remain the most efficient and popular in deriving induced pluripotent stem cells (iPSCs). For translation, it is important to silence or remove the reprogramming factors after induction of pluripotency. In this study, we design an excisable loxP-flanked lentiviral construct that a) includes all the reprogramming elements in a single lentiviral vector expressed by a strong EF-1α promoter; b) enables easy determination of lentiviral titer; c) enables transgene removal and cell enrichment using LoxP-site-specific Cre-recombinase excision and Herpes Simplex Virus-thymidine kinase/ganciclovir (HSV-tk/gan) negative selection; and d) allows for transgene excision in a colony format. A reprogramming efficiency comparable to that reported in the literature without boosting molecules can be consistently obtained. To further demonstrate the utility of this Cre-loxP/HSV-tk/gan strategy, we incorporate a non-viral therapeutic transgene (human blood coagulation Factor IX) in the iPSCs, whose expression can be controlled by a temporal pulse of Cre recombinase. The robustness of this platform enables the implementation of an efficacious and cost-effective protocol for iPSC generation and their subsequent transgenesis for downstream studies.

Analysis of gene expression to define molecular mechanisms and pathways involved in human embryonic stem cells (hESCs) proliferation and differentiations has allowed for further deciphering of the self-renewal and pluripotency characteristics of hESC. Proteins associated with hESCs were discovered through isobaric tags for relative and absolute quantification (iTRAQ). Undifferentiated hESCs and hESCs in different stages of spontaneous differentiation by embryoid body (EB) formation were analyzed. Using the iTRAQ approach, we identified 156 differentially expressed proteins involved in cell proliferation, apoptosis, transcription, translation, mRNA processing, and protein synthesis. Proteins involved in nucleic acid binding, protein synthesis, and integrin signaling were downregulated during differentiation, whereas cytoskeleton proteins were upregulated. The present findings added insight to our understanding of the mechanisms involved in hESC proliferation and differentiation.

Global gene expression analysis of human embryonic stem cells (hESCs) that differentiate into neural cells would help to further define the molecular mechanisms involved in neurogenesis in humans. We performed a comprehensive transcripteome analysis of hESC differentiation at three different stages: early neural differentiation, neural ectoderm, and differentiated neurons. We identified and validated time-dependent gene expression patterns and showed that the gene expression patterns reflect early ESC differentiation. Sets of genes are induced in primary ectodermal lineages and then in differentiated neurons, constituting consecutive waves of known and novel genes. Pathway analysis revealed dynamic expression patterns of members of several signaling pathways, including NOTCH, mTOR and Toll like receptors (TLR), during neural differentiation. An interaction network analysis revealed that the TGFβ family of genes, including LEFTY1, ID1 and ID2, are possible key players in the proliferation and maintenance of neural ectoderm. Collectively, these results enhance our understanding of the molecular dynamics underlying neural commitment and differentiation.

Overdoses are increasing in the province of Ontario, Canada, where northern communities such as Sudbury have witnessed disproportionately elevated rates, with opioid-related deaths double that of the provincial average. To address this issue, governments have implemented supervised consumption services (SCS) where people who use drugs (PWUD) can use their pre-obtained substances onsite under trained supervision. In September 2022, the city of Sudbury opened its first SCS, 'The Spot', but the site's sustainability is contingent on demonstrating benefit to PWUD and the neighboring community. We undertook a qualitative study exploring experiences among clients who used the consumption service inside The Spot. In December 2022, clients of The Spot were invited to participate in a brief survey which collected socio-demographic information and substance use profiles, followed by an in-person semi-structured qualitative interview. Participant survey and interview data were combined with administrative site utilization data provided by site staff of all clients who accessed the consumption service from September 2022 to August 2023 to examine overall service utilization and uptake. Qualitative data were analyzed using iterative thematic analysis techniques, and results were informed by common responses to research questions. The responses were narratively presented. Administrative site utilization data highlighted a relatively stable increase in uptake and utilization of the site since its inception. A total of 20 clients participated in the survey and semi-structured interviews. Participants described the importance of the site in preventing and responding to overdoses, providing a safe and comfortable environment to consume their drugs, and decreasing public drug use, which they suggested may potentially reduce stigmatization in the community. However, clients also suggested challenges, including issues regarding site operational policies that hindered consumption room utilization. Service suggestions made by clients to improve site utilization include the addition of inhalation services, relocating the site to a location in downtown Sudbury where PWUD commonly congregate, and extending operational hours. Positive impacts and recommendations can be drawn on and considered by other northern or rural communities interested in implementing similar harm reduction services., Competing Interests: The authors have declared that no competing interests exist, (Copyright: © 2023 Ali et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Deployment of solar photovoltaic panels are significantly rising to tackle adverse effects of climate change however, factors affecting output need to be categorized in addition to latitude angle and space. It is important to consider the atmospheric impact which can drastically change output power of solar panels. This study covers dust accumulation of soil, sand and ash at variable weights to foresee its effects on panel power output. Mixtures of these particles at multiple constituents were also analyzed. Experimental results indicated that clean panel gives maximum power output of 21.37W and exergy efficiency of 7.96% whereas ash accumulation showed worst results of 2.88W power output and 1.07% exergy efficiency at 700W/m2 and 50g dust accumulation. Other parameters like energy destruction, exergy losses and sustainability index were also analyzed. Trends have been illustrated in graphs along with the change in solar intensity and dust accumulations., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright: © 2023 Khan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Neuropathic pain has been characterized as chronic pain resulting from pathological damage to the sensorimotor system. Because of its complex nature, it remains refractory to most of the therapeutic interventions, and surgical intervention and physiotherapy alongside steroidal treatments remain the only treatment protocols with limited success, hence solidifying the need to find efficacious therapeutic alternatives. Emodin was used as a post-treatment for its potential to be neuroprotective in the treatment of chronic constriction injury-induced NP. The first day following surgery, Emodin treatment began, and it lasted until the 21st day. On days 3, 7, 14 and 21, all behavioral investigations were conducted. The sciatic nerve and spinal cord were extracted for further molecular examination. Emodin elevated response latency, was able to delay the onset of mechanical hyperalgesia in rats on days 7, 14, and 21 and reduced the CCI-induced paw deformation. Emodin treatment significantly reduced lipid peroxidation and NO levels while restoring the GST, GSH and catalase. It significantly improved the disorientation of the sciatic nerve and spinal cord confirmed by H & E staining and reduced inflammatory markers as observed by the quantification of COX-2, TNF-α, p-NFκb and up-regulated PPAR-γ levels by ELISA and PCR. According to the findings, Emodin has antinociceptive and anti-hyperalgesic properties, which reduced pain perception and inflammation. We also suggested the involvement of PPAR-γ pathway in the therapeutic potential of emodin in chronic nerve injury., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Badshah et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Regular monitoring of the number of various fish species in a variety of habitats is essential for marine conservation efforts and marine biology research. To address the shortcomings of existing manual underwater video fish sampling methods, a plethora of computer-based techniques are proposed. However, there is no perfect approach for the automated identification and categorizing of fish species. This is primarily due to the difficulties inherent in capturing underwater videos, such as ambient changes in luminance, fish camouflage, dynamic environments, watercolor, poor resolution, shape variation of moving fish, and tiny differences between certain fish species. This study has proposed a novel Fish Detection Network (FD_Net) for the detection of nine different types of fish species using a camera-captured image that is based on the improved YOLOv7 algorithm by exchanging Darknet53 for MobileNetv3 and depthwise separable convolution for 3 x 3 filter size in the augmented feature extraction network bottleneck attention module (BNAM). The mean average precision (mAP) is 14.29% higher than it was in the initial version of YOLOv7. The network that is utilized in the method for the extraction of features is an improved version of DenseNet-169, and the loss function is an Arcface Loss. Widening the receptive field and improving the capability of feature extraction are achieved by incorporating dilated convolution into the dense block, removing the max-pooling layer from the trunk, and incorporating the BNAM into the dense block of the DenseNet-169 neural network. The results of several experiments comparisons and ablation experiments demonstrate that our proposed FD_Net has a higher detection mAP than YOLOv3, YOLOv3-TL, YOLOv3-BL, YOLOv4, YOLOv5, Faster-RCNN, and the most recent YOLOv7 model, and is more accurate for target fish species detection tasks in complex environments., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Malik et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Chemical kinetics is a branch of chemistry that is founded on understanding chemical reaction rates. Chemical kinetics relates many aspects of cosmology, geology, and even in some cases of, psychology. There is a need for mathematical modelling of these chemical reactions. Therefore, the present research is based on chemical kinetics-based modelling and dynamics of enzyme processes. This research looks at the two-step substrate-enzyme reversible response. In the two step-reversible reactions, substrate combines with enzymes which is further converted into products with two steps. The model is displayed through the flow chart, which is then transformed into ODEs. The Atangana-Baleanu time-fractional operator and the Mittag-Leffler kernel are used to convert the original set of highly nonlinear coupled integer order ordinary differential equations into a fractional-order model. Additionally, it is shown that the solution to the investigated fractional model is unique, limited, and may be represented by its response velocity. A numerical scheme, also known as the Atangana-Toufik method, based on Newton polynomial interpolation technique via MATLAB software, is adopted to find the graphical results. The dynamics of reaction against different reaction rates are presented through various figures. It is observed that the forward reaction rates increase the reaction speed while backward reaction rates reduce it., Competing Interests: The author has declared that no competing interests exist., (Copyright: © 2023 Khan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Coronavirus Disease (COVID-19) was declared a pandemic by WHO in March 2020. Since then, additional novel coronavirus variants have emerged challenging the current healthcare system worldwide. There is an increased need for hospital care, especially intensive care unit (ICU), for the patients severely affected by the disease. Most of the studies analyzed COVID-19 infected patients in the hospitals and established the positive correlation between clinical parameters such as high levels of D-dimer, C-reactive protein, and ferritin to the severity of infection. However, little is known about the course of the ICU admission. The retrospective study carried out at University Hospital Sharjah, UAE presented here reports an integrated analysis of the biochemical and radiological factors among the newly admitted COVID-19 patients to decide on their ICU admission. The descriptive statistical analysis revealed that patients with clinical presentations such as acute respiratory distress syndrome (ARDS) (p<0.0001) at the time of admission needed intensive care. The ROC plot indicated that radiological factors including high chest CT scores (>CO-RADS 4) in combination with biochemical parameters such as higher levels of blood urea nitrogen (>6.7 mg/dL;66% sensitivity and 75.8% specificity) and ferritin (>290 μg/mL, 71.4% sensitivity and 77.8% specificity) may predict ICU admission with 94.2% accuracy among COVID-19 patients. Collectively, these findings would benefit the hospitals to predict the ICU admission amongst COVID-19 infected patients., Competing Interests: The authors have declared that no competing interests exist.

Background/objective: Despite multiple attempts, no surrogate biomarker of Parkinson disease (PD) has been definitively identified. Alternatively, identifying a non-invasive biomarker is crucial to understanding the natural history, severity, and progression of PD and to guide future therapeutic trials. Recent work highlighted alpha synuclein-containing extracellular vesicles and Poly (ADP-ribose) polymerase (PARP-1) activity as drivers of PD pathogenesis and putative PD biomarkers. This exploratory study evaluated the role of alpha-synuclein-positive extracellular vesicles and PARP-1 activity in the plasma of PD patients as non-invasive markers of the disease's severity and progression., Methods: We collected plasma of 57 PD patients (discovery cohort 20, replication cohort 37) and compared it with 20 unaffected individuals, 20 individuals with clinically diagnosed Alzheimer's disease, and 20 individuals with dementia with Lewy bodies. We analyzed alpha-synuclein-positive extracellular vesicles from platelet-free plasma by nanoscale flow cytometry and blood concentrations of poly ADP-ribose using sandwich ELISA kits., Results: Median concentration of α-synuclein extracellular vesicles was significantly higher in PD patients compared to the other groups (Kruskal-Wallis, p < .0001). In the discovery cohort, patients with higher α-synuclein extracellular vesicles had a higher Unified Parkinson Disease Rating Scale score (UPDRS III median = 22 vs. 5, p = 0.045). Seven out of 20 patients (35%) showed detectable PAR levels, with positive patients showing significantly higher levels of α-synuclein extracellular vesicles. In the replication cohort, we did not observe a significant difference in the PAR-positive cases in relationship with UPDRS III., Conclusions: Non-invasive determination of α-synuclein-positive extracellular vesicles may provide a potential non-invasive marker of PD disease severity, and longitudinal studies are needed to evaluate the role of α-synuclein-positive extracellular vesicles as a marker of disease progression., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Dr. Z. K. Wszolek is partially supported by the Mayo Clinic Center for Regenerative Medicine, Mayo Clinic in Florida Focused Research Team Program, the gifts from The Sol Goldman Charitable Trust, and the Donald G. and Jodi P. Heeringa Family, the Haworth Family Professorship in Neurodegenerative Diseases fund, and The Albertson Parkinson’s Research Foundation. He serves as PI or Co-PI on Biohaven Pharmaceuticals, Inc. (BHV4157-206 and BHV3241-301), and Neuraly, Inc. (NLY01-PD-1) grants. He serves as Co-PI of the Mayo Clinic APDA Center for Advanced Research and as external advisory board member for the Vigil Neuroscience, Inc. Dr. R. Savica receives support from the National Institute on Aging, the National Institute of Neurological Disorders and Stroke, the Parkinson’s Disease Foundation, and Acadia Pharmaceuticals. The other authors declare no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: In the era of COVID-19 where there is emphasis on the importance of wearing a mask, wearing it rightly is equally important. Therefore, the purpose of this study was to assess the knowledge, attitude and practice of wearing a mask in the general population of a developing country at three major tertiary care hospital., Materials and Methods: Participants of this cross-sectional study were patients and attendants at three major tertiary care hospital of Karachi Pakistan. Selected participants, through non-probability convenient sampling technique, were interviewed regarding knowledge, attitude, and practice of wearing mask using an Urdu translated version of a questionnaire used in an earlier study. Three summary scores (0 to 100) were computed to indicate participants' mask wearing practice, technique of putting it on, and technique of taking if off. Collected data were analyzed with the help of IBM SPSS version 19., Results: A total of 370 selected individuals were interviewed, out of which 51.9% were male and mean age was 37.65±11.94 years. For more than 90% of the participants, wearing a face mask was a routine practicing during the pandemic. The mean practice score was 65.69±25.51, score for technique of putting on a face mask was 67.77±23.03, and score of technique of taking off a face mask was 51.01±29.23. Education level of participant tends to have positive relationship with all three scores, while presence of asthma or chronic obstructive pulmonary disease (COPD) as co-morbid had negative impact on mask wearing practice., Conclusion: We have observed suboptimal knowledge, attitude and practice of wearing mask among the selected individuals. There is a continued need to spread awareness and educate general population about the importance of using a face mask, as well as the proper technique of wearing and taking off a face mask., Competing Interests: The authors have declared that no competing interests exist.