SpatialWavePredict: a tutorial-based primer and toolbox for forecasting growth trajectories using the ensemble spatial wave sub-epidemic modeling framework.

BACKGROUND: Dynamical mathematical models defined by a system of differential equations are typically not easily accessible to non-experts. However, forecasts based on these types of models can help gain insights into the mechanisms driving the process and may outcompete simpler phenomenological growth models. Here we introduce a friendly toolbox, SpatialWavePredict, to characterize and forecast the spatial wave sub-epidemic model, which captures diverse wave dynamics by aggregating multiple asynchronous growth processes and has outperformed simpler phenomenological growth models in short-term forecasts of various infectious diseases outbreaks including SARS, Ebola, and the early waves of the COVID-19 pandemic in the US. RESULTS: This tutorial-based primer introduces and illustrates a user-friendly MATLAB toolbox for fitting and forecasting time-series trajectories using an ensemble spatial wave sub-epidemic model based on ordinary differential equations. Scientists, policymakers, and students can use the toolbox to conduct real-time short-term forecasts. The five-parameter epidemic wave model in the toolbox aggregates linked overlapping sub-epidemics and captures a rich spectrum of epidemic wave dynamics, including oscillatory wave behavior and plateaus. An ensemble strategy aims to improve forecasting performance by combining the resulting top-ranked models. The toolbox provides a tutorial for forecasting time-series trajectories, including the full uncertainty distribution derived through parametric bootstrapping, which is needed to construct prediction intervals and evaluate their accuracy. Functions are available to assess forecasting performance, estimation methods, error structures in the data, and forecasting horizons. The toolbox also includes functions to quantify forecasting performance using metrics that evaluate point and distributional forecasts, including the weighted interval score. CONCLUSIONS: We have developed the first comprehensive toolbox to characterize and forecast time-series data using an ensemble spatial wave sub-epidemic wave model. As an epidemic situation or contagion occurs, the tools presented in this tutorial can facilitate policymakers to guide the implementation of containment strategies and assess the impact of control interventions. We demonstrate the functionality of the toolbox with examples, including a tutorial video, and is illustrated using daily data on the COVID-19 pandemic in the USA.

An ensemble n-sub-epidemic modeling framework for short-term forecasting epidemic trajectories: Application to the COVID-19 pandemic in the USA.

We analyze an ensemble of n-sub-epidemic modeling for forecasting the trajectory of epidemics and pandemics. These ensemble modeling approaches, and models that integrate sub-epidemics to capture complex temporal dynamics, have demonstrated powerful forecasting capability. This modeling framework can characterize complex epidemic patterns, including plateaus, epidemic resurgences, and epidemic waves characterized by multiple peaks of different sizes. We systematically assess their calibration and short-term forecasting performance in short-term forecasts for the COVID-19 pandemic in the USA from late April 2020 to late February 2022. We compare their performance with two commonly used statistical ARIMA models. The best fit sub-epidemic model and three ensemble models constructed using the top-ranking sub-epidemic models consistently outperformed the ARIMA models in terms of the weighted interval score (WIS) and the coverage of the 95% prediction interval across the 10-, 20-, and 30-day short-term forecasts. In our 30-day forecasts, the average WIS ranged from 377.6 to 421.3 for the sub-epidemic models, whereas it ranged from 439.29 to 767.05 for the ARIMA models. Across 98 short-term forecasts, the ensemble model incorporating the top four ranking sub-epidemic models (Ensemble(4)) outperformed the (log) ARIMA model 66.3% of the time, and the ARIMA model, 69.4% of the time in 30-day ahead forecasts in terms of the WIS. Ensemble(4) consistently yielded the best performance in terms of the metrics that account for the uncertainty of the predictions. This framework can be readily applied to investigate the spread of epidemics and pandemics beyond COVID-19, as well as other dynamic growth processes found in nature and society that would benefit from short-term predictions.

Structural identifiability analysis of epidemic models based on differential equations: a tutorial-based primer.

The successful application of epidemic models hinges on our ability to estimate model parameters from limited observations reliably. An often-overlooked step before estimating model parameters consists of ensuring that the model parameters are structurally identifiable from the observed states of the system. In this tutorial-based primer, intended for a diverse audience, including students training in dynamic systems, we review and provide detailed guidance for conducting structural identifiability analysis of differential equation epidemic models based on a differential algebra approach using differential algebra for identifiability of systems (DAISY) and Mathematica (Wolfram Research). This approach aims to uncover any existing parameter correlations that preclude their estimation from the observed variables. We demonstrate this approach through examples, including tutorial videos of compartmental epidemic models previously employed to study transmission dynamics and control. We show that the lack of structural identifiability may be remedied by incorporating additional observations from different model states, assuming that the system's initial conditions are known, using prior information to fix some parameters involved in parameter correlations, or modifying the model based on existing parameter correlations. We also underscore how the results of structural identifiability analysis can help enrich compartmental diagrams of differential-equation models by indicating the observed state variables and the results of the structural identifiability analysis.

Ameliorative effect of Spatoglossum asperum and its solvent fractions against acetaminophen-induced liver dysfunction in rats.

Acetaminophen (APAP) is a widely consumed drug for pain management and treatment of pyrexia. However, beyond its recommended dose, it becomes harmful for health and may induce acute liver dysfunction. Current work is designed to ameliorate the APAP induced liver toxicity which was induced in rats by giving intra-peritoneal injection of APAP (800mg/kg) dissolved in 40% polyethylene glycol at day 1 and day 14. APAP dosed/intoxicated rats orally administered either with ethanol extract of Spatoglossum asperum (200mg/kg) and its fractions including n-hexane, chloroform and methanol soluble in a dose of 150mg/kg each daily for 14 days in their respective groups. APAP dosed rats showed remarkable elevation in hepatic biomarkers viz., alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenases, total bilirubin, pro-inflammatory cytokines interleukine-6 and apoptotic protein (caspase-3). In addition, hepatic oxidative stress (lipid per oxidation and indirect nitric oxide) and antioxidant biomarkers (glutathione peroxidase, catalase and reduced glutathione) were also altered. Whereas APAP dosed rats treated with ethanol extract of S. asperum and its fractions showed amelioration in concentration of hepatic enzymes, pro-inflammatory cytokines, apoptotic protein and reduction in hepatic oxidative stress by decreasing the lipid peroxidation, indirect nitric oxide and uplifting the activities of antioxidant enzymes and protein.

Evaluation of the High Resolution Melting Approach for Detection of ß-Thalassemia Gene Mutations.

ß-Thalassemia (ß-thal), an autosomal recessive hemoglobinopathy, is one of the most common genetic disorders in Pakistan. Awareness of this disease, genetic counseling, extended family carrier screening and prenatal diagnosis (PND) are helpful in prevention and control. Currently, direct DNA sequencing and multiple amplification refractory mutation system-polymerase chain reaction (MARMS-PCR) are the methods used to detect ß-thal mutations, the latter being the most widely used. This study aimed to evaluate PCR-high resolution melting (PCR-HRM) analysis for the detection of most common ß-thal mutations that are found in Pakistan. This study was designed to identify the ß-thal mutations using PCR-HRM analysis in a total of 90 samples [blood and chorionic villus sampling (CVS)]. These samples were first screened for routine mutations by MARMS-PCR and then evaluated by PCR-HRM analysis. The results of PCR-HRM analyses were further confirmed by direct DNA sequencing and all analyses interpreted the same results in all 90 samples. Eleven cases (36.6%) were detected to carry IVS-I-5 (G>C) (HBB: c0.92 + 5G>C), six cases (20.0%) with frameshift codons (FSC) 41/42 (-TTCT) (HBB: c.126_129delCTTT), five cases (16.0%) were diagnosed with codon 15 (G>A) (HBB: c.47G>A), three cases (10.0%) were found with codon 30 (G>C) (HBB: c.93G>C), one case was diagnosed with FSC 16 (-C) (HBB: c.51delC), one with IVS-I-1 (G>T) (HBB: c0.92 + 1G>T) and one with codon 5 (-CT) (HBB: c.17_18delCT). The PCR-HRM analysis represents a less tedious and more useful method for the detection of ß-globin gene mutations.

Severe Acute Respiratory Syndrome Coronavirus 2 Transmission Potential, Iran, 2020.

To determine the transmission potential of severe acute respiratory syndrome coronavirus 2 in Iran in 2020, we estimated the reproduction number as 4.4 (95% CI 3.9-4.9) by using a generalized growth model and 3.5 (95% CI 1.3-8.1) by using epidemic doubling time. The reproduction number decreased to 1.55 after social distancing interventions were implemented.

Real-time monitoring the transmission potential of COVID-19 in Singapore, March 2020.

BACKGROUND: As of March 31, 2020, the ongoing COVID-19 epidemic that started in China in December 2019 is now generating local transmission around the world. The geographic heterogeneity and associated intervention strategies highlight the need to monitor in real time the transmission potential of COVID-19. Singapore provides a unique case example for monitoring transmission, as there have been multiple disease clusters, yet transmission remains relatively continued. METHODS: Here we estimate the effective reproduction number, Rt, of COVID-19 in Singapore from the publicly available daily case series of imported and autochthonous cases by date of symptoms onset, after adjusting the local cases for reporting delays as of March 17, 2020. We also derive the reproduction number from the distribution of cluster sizes using a branching process analysis that accounts for truncation of case counts. RESULTS: The local incidence curve displays sub-exponential growth dynamics, with the reproduction number following a declining trend and reaching an estimate at 0.7 (95% CI 0.3, 1.0) during the first transmission wave by February 14, 2020, while the overall R based on the cluster size distribution as of March 17, 2020, was estimated at 0.6 (95% CI 0.4, 1.02). The overall mean reporting delay was estimated at 6.4 days (95% CI 5.8, 6.9), but it was shorter among imported cases compared to local cases (mean 4.3 vs. 7.6 days, Wilcoxon test, p < 0.001). CONCLUSION: The trajectory of the reproduction number in Singapore underscores the significant effects of successful containment efforts in Singapore, but it also suggests the need to sustain social distancing and active case finding efforts to stomp out all active chains of transmission.

A novel sub-epidemic modeling framework for short-term forecasting epidemic waves.

BACKGROUND: Simple phenomenological growth models can be useful for estimating transmission parameters and forecasting epidemic trajectories. However, most existing phenomenological growth models only support single-peak outbreak dynamics whereas real epidemics often display more complex transmission trajectories. METHODS: We develop and apply a novel sub-epidemic modeling framework that supports a diversity of epidemic trajectories including stable incidence patterns with sustained or damped oscillations to better understand and forecast epidemic outbreaks. We describe how to forecast an epidemic based on the premise that the observed coarse-scale incidence can be decomposed into overlapping sub-epidemics at finer scales. We evaluate our modeling framework using three outbreak datasets: Severe Acute Respiratory Syndrome (SARS) in Singapore, plague in Madagascar, and the ongoing Ebola outbreak in the Democratic Republic of Congo (DRC) and four performance metrics. RESULTS: The sub-epidemic wave model outperforms simpler growth models in short-term forecasts based on performance metrics that account for the uncertainty of the predictions namely the mean interval score (MIS) and the coverage of the 95% prediction interval. For example, we demonstrate how the sub-epidemic wave model successfully captures the 2-peak pattern of the SARS outbreak in Singapore. Moreover, in short-term sequential forecasts, the sub-epidemic model was able to forecast the second surge in case incidence for this outbreak, which was not possible using the simple growth models. Furthermore, our findings support the view that the national incidence curve of the Ebola epidemic in DRC follows a stable incidence pattern with periodic behavior that can be decomposed into overlapping sub-epidemics. CONCLUSIONS: Our findings highlight how overlapping sub-epidemics can capture complex epidemic dynamics, including oscillatory behavior in the trajectory of the epidemic wave. This observation has significant implications for interpreting apparent noise in incidence data where the oscillations could be dismissed as a result of overdispersion, rather than an intrinsic part of the epidemic dynamics. Unless the oscillations are appropriately modeled, they could also give a false positive, or negative, impression of the impact from public health interventions. These preliminary results using sub-epidemic models can help guide future efforts to better understand the heterogenous spatial and social factors shaping sub-epidemic patterns for other infectious diseases.

Spatial variability in the reproduction number of Ebola virus disease, Democratic Republic of the Congo, January-September 2019.

The ongoing Ebola virus disease epidemic (August 2018─October 2019) in the Democratic Republic of the Congo, has been exacerbated by deliberate attacks on healthcare workers despite vaccination efforts. Using a mathematical/statistical modelling framework, we present the quantified effective reproduction number (Rt) at national and regional levels as at 29 September. The weekly trend in Rt displays fluctuations while our recent national-level Rt falls slightly above 1.0 with substantial uncertainty, which suggests improvements in epidemic control.

Diagnosis and prescribing pattern of antibiotics and painkillers among dentists.

PURPOSE: To examine the pattern of antibiotic and painkiller prescriptions per diagnosis by dentists. MATERIALS AND METHODS: A cross-sectional study was conducted in Karachi, Pakistan. Dentists in the outpatient departments of the Dr. Isharat-ul-Ebad Khan Institute of Oral Health Sciences (DIKIOHS) filled out a form for each patient visiting during a two-week period. The form included: personal history of the patient, i.e. name, age, sex and education, patient's complaint(s), medical history, dental history, full examination of the teeth and oral cavity, treatment need as far as different specialties are concerned, investigations, provisional diagnosis and treatment given. The WHO ATC system for drug classification was used. The number of prescriptions and defined daily doses (DDD) were recorded. RESULTS: A total of 709 patient forms (355 for male patients and 354 for female patients) were collected and included in the analysis. Of these, 123 (17%) included antibiotics and 455 (64%) painkillers. Caries/pulpitis was the most common diagnosis (n = 222; 31% of cases), of which 48 (21%) were prescribed antibiotics. Amoxicillin and metronidazole were the most common antibiotics prescribed for this diagnosis (n = 25); for caries/pulpitis diagnosis, 44 DDD/100 patients were prescribed. This was also the diagnosis for which painkiller prescription was most common (n = 191; 86%), with 102 DDD/100 patients. CONCLUSION: Our study shows the prescription pattern of antibiotics and painkillers by dentists in Pakistan for the first time. There is a clear need to emphasise correct diagnostic methods and develop contextualised prescription guidelines and educational initiatives, so that the optimum effect of antibiotics and painkillers will be achieved without compromising patients' health.

Association of the use of bacterial cell wall synthesis Inhibitor drugs in early childhood with the Developmental Defects of Enamel.

OBJECTIVE: Our objective of the study was to determine the association between frequent use of Penicillins and Cephalosporins with developmental defects of enamel in pediatric age group. METHODS: This is a cross sectional study, conducted at Ziauddin University. A total of 367 children, having the history of either Penicillin or Cephalosporin exposure were included. The parents of children were asked to complete a questionnaire related to disease and drug history. Dental examination was carried out to assess the hypomineralization in tooth enamel based on modified Developmental Defects of Enamel (DDE) index. RESULTS: Out of 367 children, 124 (34%) were males and females were 243(66%). In the study group 22.6% (n= 83) of children were found to be hypomineralized. The maximum type of teeth defects were diffused opacities that was 12.0% (n=44). The statistically significant association (p-value < 0.05) was found between frequency of antibiotic use and hypomineralization for most teeth. Children who were exposed to either Penicillins or Cephalosporin in early childhood showed significant (p-value < 0.002) hypomineralized enamel. CONCLUSION: This study concludes that frequent use of antibiotics such as penicillins and cephalosporins has positive association with enamel hypomineralization in developing tooth structure.

Gemigliptin, a potent selective dipeptidyl peptidase 4 inhibitor, protects endothelial progenitor cells by oxidative stress via caspase-3 dependent pathway.

Endothelial progenitor cells (EPCs) are exclusive players in vasculogenesis and endothelial regeneration. EPCs are of two types and their differentiation is mediated by different growth factors. A decrease in EPC number and function causes cardiovascular abnormalities and reduced angiogenesis. Various studies has documented a role of EPCs in diabetes. EPCs treatment with different drugs improve insulin secretion but causes other abnormalities. In vivo and in vitro studies have reported anti glycation effect of gemigliptin but no data is available on in vitro effect of gemigliptin on EPC number and functional credibility. The current study was aimed to find an in vitro effect of gemigliptin on EPC number and function along with an effective treatment dose of gemigliptin. EPCs were isolated, cultured and phenotypically characterized using Dil- AcLDL and ulex-lectin fluorescence staining. EPCs were then treated with different doses of Zemiglo and their viability analyzed with viability assay using water-soluble tetrazolium salt (WST-1), by Annexin V and Propidium Iodide (PI) staining, senescence-associated beta-galactosidase (SA-ß-gal) staining, western blot and Flow cytometric analysis of apoptotic signals. The results demonstrated that the isolated EPCs has typical endothelial phenotypes. And these EPCs were of two types based on morphology i.e., early and late EPCs. Gemigliptin dose dependently improved the EPCs morphology and increased EPCs viability, the most effective dose being the 20 µM. Gemigliptin at 10 µM, 20 µM and 50 µM significantly increased the BCL-2 levels and at 20 µM significantly decreased the Caspase-3 levels in EPCs. In conclusion, gemigliptin dose dependently effects the EPCs viability and morphology through Caspase-3 signaling. Our results are the first report of gemigliptin effect on EPC viability and morphology.

Empowering Minds and Bodies: The Impact of Exercise on Multiple Sclerosis and Cognitive Health.

Multiple sclerosis (MS) is a global health concern affecting around 2.6 million people. It is characterised by neural inflammation, myelin breakdown and cognitive decline. Cognitive impairment, especially reduced cognitive processing speed (CPS), which affects up to 67% of MS patients and frequently manifests before mobility concerns, is one of the disease's most serious side effects. Effective adaptation and the application of cognitive rehabilitation treatments depend on the early diagnosis of cognitive impairment. Although pharmaceutical therapies have some drawbacks, endurance training has become a promising alternative. Intensity-controlled endurance exercise has the ability to delay the onset of MS symptoms and enhance cognitive function. Exercise has also been shown to have neuroprotective effects in a number of neurological disorders, including MS, Parkinson's disease and stroke. This includes both aerobic and resistance training. A mix of aerobic exercise and weight training has shown promise, especially for people with mild cognitive impairment, but according to recent studies any amount of physical activity is beneficial to cognitive performance. In conclusion, this in-depth analysis highlights the crucial part endurance exercise plays in treating MS-related cognitive impairment. It improves not only neurological health in general but also cognitive performance. Exercise can help control MS in a way that dramatically improves quality of life and well-being.

Exploring the Role of Licorice and Its Derivatives in Cell Signaling Pathway NF-κB and MAPK.

Licorice is a therapeutic herb in traditional Chinese herbal medicine. Licorice is considered as an anti-inflammatory agent due to its suppression and inhibition of inflammatory pathways. Licorice has many bioactive compounds such as glycyrrhetinic acid, glycyrrhizin, liquiritigenin, and isoliquirtigenin which are principally accountable for its therapeutic benefits. These bioactive components reduce inflammation by preventing the activation of important inflammatory pathways including mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB). As a result of this tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß) and interleukin-6 (IL-6) are among the proinflammatory cytokines whose production is inhibited. Components present in licorice inhibit the activation by suppressing the IκBα phosphorylation and degradation. Moreover, licorice compounds also attenuate the MAPK signaling cascades by inhibiting the MAPK kinase phosphorylation and downstream MAPKs such as extracellular signal-regulated kinase (ERK), p38 MAPK, and c-Jun N-terminal kinase (JNK). The present review focuses on the current understanding of licorice effect on the NF-κB and MAPK inflammatory cell signaling pathways at molecular level. Furthermore, emerging evidence suggested that licorice-derived bioactive compounds may attenuate the molecular mechanism which is associated with inflammation, providing the additional insights into the therapeutic potential. Further studies explained the precise molecular mechanism at the cellular level underlying the licorice anti-inflammatory effect and potential application in managing inflammatory disorders. In conclusion, licorice has a complex mode of action and is a valuable natural anti-inflammatory. Its natural origin and effectiveness in clinical applications make it an intriguing topic for additional study. As licorice becomes more widely used in medicine, future research should focus on refining its formulations to optimize therapeutic advantages.

The Comparative Study of Serum Estrogen and Lipid Profile in Pre- and Post-menopausal Women as Atherosclerosis Risk Factors in Pakistan.

BACKGROUND: Menopause signifies the eternal termination of menstruation in women as a consequence of ovarian action loss, typically occurring around the age of 51 years. Cardiovascular disease is the leading cause of death among post-menopausal women, which may be due to lower levels of estrogen and lipid profile. The present study was undertaken to evaluate serum estrogen and lipid profile status to assess the risk of atherosclerosis in both pre- and post-menopausal women. OBJECTIVES: The objective of this study is to explore the relationship between estrogen and lipid levels of women in pre- and post-menopausal stages. METHODOLOGY: A comparative cross-sectional study was conducted at Railway General Hospital Rawalpindi. A total of 100 participants were included of which 50 were pre-menopausal and 50 were post-menopausal women. Laboratory examination and questionnaires from the study population were used for data collection. Through the enzymatic method, serum cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein (HDL) were assessed. Serum very low-density lipoprotein (VLDL) levels were calculated via Friedwald's components VLDL=TG/5.0. An enzyme-linked immunosorbent assay kit was used for estrogen measurement. For statistical analysis, Student's t-test and the Pearson correlation test were used. RESULTS: Women after menopause have significantly high serum cholesterol, low-density lipoproteins, VLDLs, and triglycerides while HDL-c levels were significantly low (P<0.001). Levels of estrogen were low in post-menopausal females (P<0.001) as compared to menstruating women. Estrogen with HDL concentrations showed a positive correlation with an r value of 0.08556 while LDL levels showed a negative correlation with a r value of -0.26219. CONCLUSION: This comparative study explores the relationship between estrogen and lipid levels in pre- and post-menopausal women. Low estrogen with changed lipid variables was observed. Decreased cardiovascular protective HDL-c marks that menopause is a phase that acts as an independent risk factor for atherosclerosis.

GrowthPredict: A toolbox and tutorial-based primer for fitting and forecasting growth trajectories using phenomenological growth models.

Simple dynamic modeling tools can help generate real-time short-term forecasts with quantified uncertainty of the trajectory of diverse growth processes unfolding in nature and society, including disease outbreaks. An easy-to-use and flexible toolbox for this purpose is lacking. This tutorial-based primer introduces and illustrates GrowthPredict, a user-friendly MATLAB toolbox for fitting and forecasting time-series trajectories using phenomenological dynamic growth models based on ordinary differential equations. This toolbox is accessible to a broad audience, including students training in mathematical biology, applied statistics, and infectious disease modeling, as well as researchers and policymakers who need to conduct short-term forecasts in real-time. The models included in the toolbox capture exponential and sub-exponential growth patterns that typically follow a rising pattern followed by a decline phase, a common feature of contagion processes. Models include the 1-parameter exponential growth model and the 2-parameter generalized-growth model, which have proven useful in characterizing and forecasting the ascending phase of epidemic outbreaks. It also includes the 2-parameter Gompertz model, the 3-parameter generalized logistic-growth model, and the 3-parameter Richards model, which have demonstrated competitive performance in forecasting single peak outbreaks. We provide detailed guidance on forecasting time-series trajectories and available software ( https://github.com/gchowell/forecasting_growthmodels ), including the full uncertainty distribution derived through parametric bootstrapping, which is needed to construct prediction intervals and evaluate their accuracy. Functions are available to assess forecasting performance across different models, estimation methods, error structures in the data, and forecasting horizons. The toolbox also includes functions to quantify forecasting performance using metrics that evaluate point and distributional forecasts, including the weighted interval score. This tutorial and toolbox can be broadly applied to characterizing and forecasting time-series data using simple phenomenological growth models. As a contagion process takes off, the tools presented in this tutorial can help create forecasts to guide policy regarding implementing control strategies and assess the impact of interventions. The toolbox functionality is demonstrated through various examples, including a tutorial video, and the examples use publicly available data on the monkeypox (mpox) epidemic in the USA.

SubEpiPredict: A tutorial-based primer and toolbox for fitting and forecasting growth trajectories using the ensemble n-sub-epidemic modeling framework.

An ensemble n-sub-epidemic modeling framework that integrates sub-epidemics to capture complex temporal dynamics has demonstrated powerful forecasting capability in previous works. This modeling framework can characterize complex epidemic patterns, including plateaus, epidemic resurgences, and epidemic waves characterized by multiple peaks of different sizes. In this tutorial paper, we introduce and illustrate SubEpiPredict, a user-friendly MATLAB toolbox for fitting and forecasting time series data using an ensemble n-sub-epidemic modeling framework. The toolbox can be used for model fitting, forecasting, and evaluation of model performance of the calibration and forecasting periods using metrics such as the weighted interval score (WIS). We also provide a detailed description of these methods including the concept of the n-sub-epidemic model, constructing ensemble forecasts from the top-ranking models, etc. For the illustration of the toolbox, we utilize publicly available daily COVID-19 death data at the national level for the United States. The MATLAB toolbox introduced in this paper can be very useful for a wider group of audiences, including policymakers, and can be easily utilized by those without extensive coding and modeling backgrounds.

Endothelial Progenitor Cells: A Brief Update.

An enormous amount of current data has suggested involvement of endothelial progenitor cells (EPCs) in neovasculogenesis in both human and animal models. EPC level is an indicator of possible cardiovascular risk such as Alzheimer disease. EPC therapeutics requires its identification, isolation, differentiation and thus expansion. We approach here the peculiar techniques through current and previous reports available to find the most plausible and fast way of their expansion to be used in therapeutics. We discuss here the techniques for EPCs isolation from different resources like bone marrow and peripheral blood circulation. EPCs have been isolated by methods which used fibronectin plating and addition of various growth factors to culture media. Particularly, the investigations which tried to enhance EPC differentiation while inducing with growth factors and endothelial nitric oxide synthase are shared. We also include the cryopreservation and other storage methods of EPCs for a longer time. Sufficient amount of EPCs are required in transplantation and other therapeutics which signifies their in vitro expansion. We highlight the role of EPCs in transplantation which improved neurogenesis in animal models of ischemic stroke and human with acute cerebral infarct in the brain. Accumulatively, these data suggest the exhilarating route for enhancing EPC number to make their use in the clinic. Finally, we identify the expression of specific biomarkers in EPCs under the influence of growth factors. This review provides a brief overview of factors involved in EPC expansion and transplantation and raises interesting questions at every stage with constructive suggestions.

A MATLAB toolbox to fit and forecast growth trajectories using phenomenological growth models: Application to epidemic outbreaks.

Background: Simple dynamic modeling tools can be useful for generating real-time short-term forecasts with quantified uncertainty of the trajectory of diverse growth processes unfolding in nature and society, including disease outbreaks. An easy-to-use and flexible toolbox for this purpose is lacking. Results: In this tutorial-based primer, we introduce and illustrate a user-friendly MATLAB toolbox for fitting and forecasting time-series trajectories using phenomenological dynamic growth models based on ordinary differential equations. This toolbox is accessible to various audiences, including students training in time-series forecasting, dynamic growth modeling, parameter estimation, parameter uncertainty and identifiability, model comparison, performance metrics, and forecast evaluation, as well as researchers and policymakers who need to conduct short-term forecasts in real-time. The models included in the toolbox capture exponential and sub-exponential growth patterns that typically follow a rising pattern followed by a decline phase, a common feature of contagion processes. Models include the 2-parameter generalized-growth model, which has proved useful to characterize and forecast the ascending phase of epidemic outbreaks, and the Gompertz model as well as the 3-parameter generalized logistic-growth model and the Richards model, which have demonstrated competitive performance in forecasting single peak outbreaks.The toolbox provides a tutorial for forecasting time-series trajectories that include the full uncertainty distribution, derived through parametric bootstrapping, which is needed to construct prediction intervals and evaluate their accuracy. Functions are available to assess forecasting performance across different models, estimation methods, error structures in the data, and forecasting horizons. The toolbox also includes functions to quantify forecasting performance using metrics that evaluate point and distributional forecasts, including the weighted interval score. Conclusions: We have developed the first comprehensive toolbox to characterize and forecast time-series data using simple phenomenological growth models. As a contagion process takes off, the tools presented in this tutorial can facilitate policymaking to guide the implementation of control strategies and assess the impact of interventions. The toolbox functionality is demonstrated through various examples, including a tutorial video, and is illustrated using weekly data on the monkeypox epidemic in the USA.

Factors Associated with Chikungunya Infection among Pregnant Women in Grenada, West Indies.

Neonates are vulnerable to vector-borne diseases given the potential for mother-to-child congenital transmission. To determine factors associated with chikungunya virus (CHIKV) infection among pregnant women in Grenada, West Indies, a retrospective cohort study enrolled women who were pregnant during the 2014 CHIKV epidemic. In all, 520/688 women (75.5%) were CHIKV IgG positive. Low incomes, use of pit latrines, lack of home window screens, and subjective reporting of frequent mosquito bites were associated with increased risk of CHIKV infection in bivariate analyses. In the multivariate modified Poisson regression model, low income (adjusted relative risk [aRR]: 1.05 [95% CI: 1.01-1.10]) and frequent mosquito bites (aRR: 1.05 [95% CI: 1.01-1.10]) were linked to increased infection risk. In Grenada, markers of low socioeconomic status are associated with CHIKV infection among pregnant women. Given that Grenada will continue to face vector-borne outbreaks, interventions dedicated to improving living conditions of the most disadvantaged will help reduce the incidence of arboviral infections.