Regulation of toxins and bioregulators under the Chemical Weapons Convention and the Biological and Toxin Weapons Convention

In this paper we highlight how the apparent double coverage of toxins and bioregulators by both the Biological and Toxin Weapons Convention(BTWC)and the Chemical Weapons Convention(CWC)in fact masks a regulatory gap that has left such potentially dangerous agents neglected by both the control regimes during a period of rapid advances in relevant chemical,life and associated sciences and technologies.We first review what toxins,bioregulators and other mid-spectrum agents are and why they are of such concern and then examine how they are regulated under the BTWC and CWC.This paper then examines an illustrative range of contemporary chemical and life science research and associated activities of concern drawn from case study research on China,India,Iran,Russia,Syria and the United States,and assesses how the CWC and BTWC States Parties have inadequately addressed these threats.We then examine how both the CWC and BTWC Review Conferences failed to address these long-term challenges,and we end by providing a series of recommendations for how both regimes can be strengthened in this area.

Structure-based discovery of F.religiosa phytochemicals as potential inhibitors against Monkeypox(mpox)viral protein

Outbreaks of Monkeypox(mpox)in over 100 non-endemic countries in 2022 represented a serious global health concern.Once a neglected disease,mpox has become a global public health issue.A42R profilinlike protein from mpox(PDB ID:4QWO)represents a potential new lead for drug development and may interact with various synthetic and natural compounds.In this report,the interaction of A42R profilinlike protein with six phytochemicals found in the medicinal plant Ficus religiosa(abundant in India)was examined.Based on the predicted and compared protein–ligand binding energies,biological properties,IC_(50) values and toxicity,two compounds,kaempferol(C-1)and piperine(C-4),were selected.ADMET characteristics and quantitative structure–activity relationship(QSAR)of these two compounds were determined,and molecular dynamics(MD)simulations were performed.In silico examination of the kaempferol(C-1)and piperine(C-4)interactions with A42R profilin-like protein gave best-pose ligandbinding energies of–6.98 and–5.57 kcal/mol,respectively.The predicted IC_(50) of C-1 was 7.63 lM and 82 lM for C-4.Toxicity data indicated that kaempferol and piperine are non-mutagenic,and the QSAR data revealed that piperlongumine(5.92)and piperine(5.25)had higher log P values than the other compounds examined.MD simulations of A42R profilin-like protein in complex with C-1 and C-4 were performed to examine the stability of the ligand–protein interactions.As/C and C-4 showed the highest affinity and activities,they may be suitable lead candidates for developing mpox therapeutic drugs.This study should facilitate discovering and synthesizing innovative therapeutics to address other infectious diseases.

Computational modeling and inhibition of SARS-COV-2 Papain-like protease enzyme:A potential therapeutic approach for COVID-19

This study aims to investigate the potential impact of inhibitors targeting the papain-like protease(PLpro)of SARS-CoV-2 on viral replication and the host immune response.A mathematical model was developed to simulate the interaction among susceptible cells,infected cells,PLpro,and immune cells,incorporating data on PLpro inhibition.Through numerical simulations using MATLAB,the model parameters were estimated based on available statistical data.The results indicate that strategically positioned inhibitors could impede the virus’s access to host cellular machinery,thereby enhancing the immune response and gradually reducing susceptible and infected cells over time.The dynamics of the viral enzyme PLpro showed reduced activity with the introduction of the inhibitor,leading to a decline in viral replication.Moreover,the immune cell population exhibited functional recovery as the inhibitor suppressed PLpro activity.These findings suggest that inhibitors targeting PLpro may serve as therapeutic interventions against SARS-CoV-2 by inhibiting viral replication and bolstering the immune response.

A mathematical model for a disease outbreak considering waningimmunity class with nonlinear incidence and recovery rates

In the spread of infectious diseases,intervention levels play a crucial role in shaping interactions between healthy and infected individuals,leading to a nonlinear transmission process.Additionally,the availability of medical resources limits the recovery rate of infected patients,adding further nonlinear dynamics to the healing process.Our research introduces novelty by combining nonlinear incidence and recovery rates alongside waning immunity in an epidemic model.We present a modified SIRW-type model,examining the epidemic problem with these factors.Through analysis,we explore conditions for non-endemic and co-existing cases based on the basic reproduction ratio.The local stability of equilibria is verified using the Routh-Hurwitz criteria,while global stability is assessed using Lyapunov functions for each equilibrium.Furthermore,we investigate bifurcations around both non-endemic and co-existing equilibria.Numerically,we give some simulations to support our analytical findings.

Dynamic evolution of an SVEIR model with variants and non-pharmaceutical interventions for controlling COVID-19

The epidemiological characteristics and distributions of two epidemics in Fujian Province of Southeast China were attributed to the complex interactions among variant,host,and non-pharmaceutical interventions(NPIs).All reported cases in the Putian epidemic(September 8–October 2,2021,Delta variant B.1.617.2)and Fuzhou epidemic(October 22–November 18,2022,Omicron variant BA.5.2)were classified by sex,age group,occupation,and location in this study.Using surveillance data from the Fujian Provincial Center for Disease Control and Prevention,we established a virus-oriented SVEIR(Susceptible–Vaccinated–Exposed–Infected–Recovered)model to investigate the dynamic evolution features of these two variants and the effects of NPIs.The optimal simulations were carried out with variants and scenario investigations.The scenario investigations showed that NPIs significantly reduced the transmission risk and infection scales of COVID-19,and that the Omicron variant was more infectious than the Delta variant.Moreover,the dynamic investigations revealed the increasing tendencies from Delta to Omicron,such as the basic reproduction number,infection rate,percentage of high-risk cases,and the growth rate.Decreasing tendencies were also identified,such as the average recovery period,the awareness delay,and the percentage of symptomatic cases.This study highlighted that NPIs played critical roles in successfully containing the two epidemics.Such interventions are strongly recommended to public health policymakers.

Modeling and optimal control of COVID-19 with comorbidity and three-dose vaccination in Indonesia

This paper presents and examines a COVID-19 model that takes comorbidities and up to three vaccine doses into account.We analyze the stability of the equilibria,examine herd immunity,and conduct a sensitivity analysis validated by data on COVID-19 in Indonesia.The disease-free equilibrium is locally and globally asymptotically stable whenever the basic reproduction number is less than one,while an endemic equilibrium exists and is globally asymptotically stable when the number is greater than one.Subsequently,the model incorporates two effective measures,namely public education and enhanced medical care,to determine the most advantageous approach for mitigating the transmission of the disease.The optimal control model is then determined using Pontryagin’s maximum principle.The integrated control strategy is the best method for reliably safeguarding the general population against COVID-19 infection.Cost evaluations and numerical simulations corroborate this conclusion.

Analyzing co-infection dynamics:A mathematical approach using fractional order modeling and Laplace-Adomian decomposition

The co-infection of HIV and COVID-19 is a pressing health concern,carrying substantial potential consequences.This study focuses on the vital task of comprehending the dynamics of HIV-COVID-19 coinfection,a fundamental step in formulating efficacious control strategies and optimizing healthcare approaches.Here,we introduce an innovative mathematical model grounded in Caputo fractional order differential equations,specifically designed to encapsulate the intricate dynamics of co-infection.This model encompasses multiple critical facets:the transmission dynamics of both HIV and COVID-19,the host’s immune responses,and the influence of treatment interventions.Our approach embraces the complexity of these factors to offer an exhaustive portrayal of co-infection dynamics.To tackle the fractional order model,we employ the Laplace-Adomian decomposition method,a potent mathematical tool for approximating solutions in fractional order differential equations.Utilizing this technique,we simulate the intricate interactions between these variables,yielding profound insights into the propagation of co-infection.Notably,we identify pivotal contributors to its advancement.In addition,we conduct a meticulous analysis of the convergence properties inherent in the series solutions acquired through the Laplace-Adomian decomposition method.This examination assures the reliability and accuracy of our mathematical methodology in approximating solutions.Our findings hold significant implications for the formulation of effective control strategies.Policymakers,healthcare professionals,and public health authorities will benefit from this research as they endeavor to curtail the proliferation and impact of HIV-COVID-19 co-infection.

Addressing poxvirus challenges in the Middle East to enhance biosafety and biosecurity measures

The emergence and zoonotic transmission of poxviruses in the Middle East have been recognized as complex public health issues.Poxviruses,a vast family of DNA viruses,can infect many hosts,including animals and humans.The Middle East has had multiple epidemics of poxvirus infections(e.g.,Monkeypox,Smallpox,and Camelpox)that have raised concerns owing to their detrimental effects on livestock,wildlife,and sporadic human cases.This review aims to thoroughly examine the complexity of the epidemiological patterns,intricate genetic diversity,and several contributing factors that support the emergence and zoonotic transmission of poxviruses in the Middle East.Several aspects of poxviruses contribute to the emergence of endemics and zoonotic breakouts,such as the complex nature of human-animal interactions,environmental changes,and their subtle capacity for viral adaptability.This review was compiled in the hopes of contributing to the current understanding of poxvirus biology and its implications for human and animal health in the Middle East.We provide a comprehensive overview of the most common poxviruses in the Middle East,including their classification,structure,replication cycle,pathogenesis,route of transmissions,and of how the Middle East has developed ways to mitigate these biological threats.

Chi-square automatic interaction detection(CHAID)analysis of the use of safety goggles and face masks as personal protective equipment(PPE)to protect against occupational biohazards

Background:This study represents the first Spanish investigation to rigorously evaluate compliance with the use of safety goggles and face masks as essential personal protective equipment(PPE)in companies with workplaces involving exposure to biological agents.Objectives:This study aimed to examine the degree of use of face masks and safety goggles as personal protective equipment(PPE),the factors that influence their use,and the profile of workers exposed to occupational biological agents in Spanish companies in the health sector,farming sector,meat industry,waste treatment plants,food industry,and veterinary centers.Methods:We conducted a cross-sectional descriptive study involving 590 Spanish workers from 51 companies.We developed a 34-item questionnaire to assess workers’perception of risk related to exposure to biological agents in their workplaces.Among the questions,three were designed to measure the degree of use of key protective equipment in sectors with biological agent exposure:protective gloves,safety goggles or face masks.We only analyzed safety goggles and face masks.We performed various statistical analyses,including Cronbach’s alpha,frequency of endorsement,content validity ratio using Lawshe’s method,varimax rotation,the Kaiser-Meyer-Olkin test,and Bartlett’s sphericity test,to assess the internal consistency and reliability of the questionnaire.Additionally,we employed a chi-square automatic interaction detection(CHAID)segmentation analysis,using workers’responses regarding their attitudes toward safety goggles and face mask usage as PPE for protection against biological risks,with demographic variables as independent factors.Results:In the current study,CHAID analysis revealed that workers exposed to group 2 biological agents used more safety goggles and face shields compared with workers exposed to other groups of biological agents.Moreover,workers in laboratories and the food industry used face masks more than workers of other sectors.Conclusion:The CHAID analysis in the current study indicated that workers exposed to biological agents from both group 2 and group 3 demonstrated satisfactory levels of compliance and utilization of protective masks,surpassing their counterparts in terms of usage.Workers in the food and laboratory industries had subpar compliance with preventive measures,and employees from companies with internal health and safety departments exhibited significant adherence to workplace mask usage,safeguarding themselves against biological risks.

Stability analysis of a fractional-order monkeypox epidemic model with quarantine and hospitalization

The monkeypox epidemic has become a global health issue due to its rapid transmission involving nonhuman-to-human transmission in nonendemic areas.Various actions,such as quarantine,vaccination,and hospitalization,have been implemented by worldwide governments.Given the relatively high cost and strict implementation of vaccination,our focus lies on quarantine and hospitalization.In this paper,we study the monkeypox epidemic involving quarantine and hospitalization through fractionalorder mathematical modeling.The proposed model considers six classes of human populations(susceptible,exposed,infected,quarantined,hospitalized,and recovered)and three classes of nonhuman populations(susceptible,exposed,and infected).The basic properties of the model have been investigated,and its equilibrium points have been obtained,namely monkeypox-free,nonhuman-free endemic,and endemic.We have derived the basic reproduction numbers for human-to-human and nonhuman-tononhuman transmissions,denoted as R0h and R0n respectively.The existence and stability(both locally and globally)of each equilibrium point depend on R0h and R0n relative to unity.We performed calibration and forecasting of the model on the weekly monkeypox case data of the human population in the United States of America from June 1 to September 23,2022.Research findings indicate that the fractional-order model shows better calibration and forecasting compared to the corresponding firstorder model based on the root mean square error.Furthermore,the best-fitting model calibration indicates R0=maxfR0h;R0ng>1,suggesting the potential for endemic conditions in humans.However,the best forecasting shows R0<1,possibly due to various policies such as vaccination.Given the relative cost and stringency of vaccination implementation for monkeypox control,we perform numerical simulations and sensitivity analyses on the basic reproduction number,particularly focusing on the impact of quarantine and hospitalization rates.Simulations and sensitivity analysis indicate that simultaneous increases in quarantine and hospitalization rates can reduce the basic reproduction number R0h below unity.Consequently,the monkeypox epidemic can be eradicated.Moreover,fractional-order derivative plays a crucial role in determining the spikes of monkeypox cases and the rapidity at which the disease undergoes either endemicity or extinction.Considerations of memory effects,quarantine,and hospitalization have a significant impact on monkeypox modeling studies,especially in capturing biological phenomena.

The association between mycotic pneumonia and neonatal septicemia

Background:Candida species are the fourth most common etiological agents of late-onset infection in the neonatal intensive care unit(NICU)and are responsible for considerable morbidity and mortality.Objectives:From November 2023 to February 2024,we investigated the association of mycotic pneumonia with septicemia in 60 neonates,and their roles of mycotic pneumonia in the morbidity and mortality of neonates in two NICUs in the Al-Ramadi Teaching Hospital for Maternity and Children.Methods:All infants in this study had been diagnosed with septicemia and treated with empirical antimicrobial therapy.An early morning nasogastric tube(NG-tube)was used to collect swallowed sputum by suction for culture and sensitivity testing.Results:The average white blood count for the neonates was 8547±5884.5 cells/mm^(2).The mean C-reactive protein was 39.3±26 mg/l,the mean serum albumin was 2.9±0.2 g/dl and the positive bacterial blood culture was 28(46.7%).9(15%)neonates died during the study period.The NG-tube culture identified fungal growth in all samples.Of these,49(81.6%)were identified as Candida albicans,6(10%)as Candida tropicalis,and 5(8.3%)as Cryptococcus laurentii.The bacterial culture results from the NG-tube samples identified 13(21.6%)patients with gram-positive bacteria and 47(78.3%)with gram-negative bacteria.Conclusion:We found a prevalence of Candida spp.among neonates in addition to microbial oxygen tube contamination,indicating a biosafety breach in the neonatal unit.Mycotic infection requires global attention as a probable cause of respiratory failure in neonatal septicemia.

Development and assessment of cutting-edge biotechnologies

The emergence of advanced biotechnologies has intensified in recent years.The rapid development of these biotechnologies has had a wide and profound impact globally,with the majority on the frontier of biosecurity technologies.The global biosecurity situation is currently highly challenging,with the characteristics of internationalization,extremely serious harm,and complex development.The misuse and abuse of biotechnologies are common,which thereby endanger biosecurity.The international community and governments have attached great importance to cutting-edge biotechnologies and are implementing laws and regulations to control and prevent biosecurity-related influences.By tracking the frontier progress of the new technologies generated from gene editing,gene drives,synthetic biology,and related cross-disciplines as applied in the biosecurity field,we analyzed the development trends in biotechnologies and their potential influence.On the one hand,this paper proposes that there is an urgent need for global cooperation to formulate management,control strategies,and measures for cutting-edge technologies in biosecurity to jointly promote their sound development.On the other hand,the international community should jointly shoulder the responsibility for safeguarding biosecurity and restrict the biotechnologies to rational applications within legal and ethical frameworks.This paper aims to provide a reference for the prevention of misuse and abuse of biotechnologies and support global cooperation in biosecurity governance.

Emerging bedaquiline resistance:A threat to the global fight against drug-resistant tuberculosis

Bedaquiline resistance is increasingly observed in the treatment of rifampicin-resistant tuberculosis(TB),yet standardized regimens for managing bedaquiline-resistant TB are lacking.Studies indicate a high proportion of bedaquiline-resistant cases have previously been treated for TB,and often involve strains resistant to quinolones.Regular monitoring of the culture status in patients receiving bedaquiline resistance treatment is advised.Methods such as experimental evolution,protein modeling,genome sequencing,and phenotypic analysis have been instrumental in identifying the mechanisms of bedaquiline resistance.Specifically,variants in the Rv0678 transcriptional repressor of the MmpS5-MmpL5 efflux system are linked to this type of resistance.Bayesian probability estimates show promise in determining the genotypic–phenotypic association for bedaquiline resistance,suggesting potential utility in clinical practice.Future research should explore the practical application of Bayesian probabilities in managing bedaquiline resistance.Sequencing-based technologies are anticipated to play a vital role in the early detection and management of drug-resistant TB strains.

Effectiveness of chemical inactivation of infectious liquid biological waste:A randomized sample study of research laboratories in Switzerland

Laboratory wastewater has been suggested as an important escape route for microorganisms from research environments.Likely reasons for the unintentional release of laboratory organisms are shortcomings in the handling of infectious liquid biological waste(LBW)and inadequate inactivation procedures.We developed an analytical approach to investigate the use of chemical inactivation(CI)procedures in Swiss research laboratories by on-site random sampling of presumably inactivated infectious LBW and testing it for the presence of infectious lentiviruses(HIV-1)and adenoviruses(AdV).In addition,standard operating procedures(SOPs)for CI were collected and evaluated,and laboratorystaff knowledge of CI processes was assessed using a questionnaire.Although we found several deficiencies in the technical knowledge and training of laboratory staff on the CI of LBW,as documented by 27 returned questionnaires,no infectious viruses were detected in the eight LBW samples collected.Whilst we acknowledge that the number of LBW samples and SOPs is small,we conclude that CI of LBW containing infectious lentiviruses and adenoviruses does not result in the systematic release of considerable amounts of infectious viruses into the environment from research laboratories in Switzerland.

Exploring the Interplay Between Social Awareness and the Use of Bed Nets in a Malaria Control Program

This research aims to understand the effect of human awareness and the use of bed nets on malaria control programs.A deterministic host-vector mathematical model was utilized and simplified using the Quasi-Steady State Approximation,assuming the mosquito population is at equilibrium due to its fast,dynamic behavior.The model reveals two equilibrium states:the malaria-free equilibrium and the endemic equilibrium.The malaria-free equilibrium is locally asymptotically stable when the basic reproduction number is less than one and unstable if it is larger than one.Conversely,the malaria-endemic equilibrium is unique and stable if the reproduction number exceeds one and does not exist otherwise.Based on incidence data from Papua,parameter estimation and sensitivity analyses indicate that human awareness and the use of bed nets significantly reduce the reproduction number.To address budget constraints for interventions,the model was reformulated as an optimal control problem,characterized using the Pontryagin Maximum Principle,and solved with the forward–backward sweep method.Numerical experiments were conducted to assess the impact of various scenarios on the malaria control program.Cost-effectiveness analyses employing ACER,ICER,and IAR metrics suggest that while the combined implementation of awareness campaigns and bed nets effectively reduces infections,it incurs high costs.In contrast,implementing human awareness campaigns alone emerges as the best strategy based on ACER,ICER,and IAR standards.This study demonstrates that enhancing human awareness and promoting the use of bed nets are effective strategies for controlling malaria.However,due to budget constraints,focusing solely on awareness campaigns proves to be the most cost-effective intervention.This approach not only reduces malaria transmission but also optimizes resource allocation,highlighting the importance of targeted educational programs in public health initiatives for malaria control.

Mosquito-borne diseases:Assessing risk and strategies to control their spread in the Middle East

Mosquito-borne diseases(MBDs),like malaria and mosquito-borne viruses(MBVs),have caused the deaths of millions of people.Their threat resides in the variety of transmission modes that they possess,along with the wide selection of favorable hosts,such as humans,cattle,and rodents.MBDs are increasingly gaining a reputation as one of the most dangerous threats to public health in recent years.Mosquito numbers have been increasing in recent years as a result of multiple factors such as climate change and deforestation.This situation highlights the urgent need for actions to mitigate mosquito and MBD pathogen distributions.In the Middle East,many outbreaks of MBDs have been reported in the region.However,there are no reports of any endemic episodes of MBDs.The Middle East has faced many challenges over the years;however,the Syrian refugee crisis may be strongly related to the spread of infectious diseases.As mass gatherings and high-density populations are common features in the region,it is possible to understand why MBDs can spread easily.This review summarizes the state of MBDs in the Middle East,highlighting the different types of MBDs that have been reported in the region and discussing how to move forward with controlling their spread and limiting the risks they pose.According to the data reported by the electronic State Parties Self-Assessment Annual Reporting Tool(e-SPAR),the capacity to anticipate MBVs varies among Middle East countries.Therefore,the Middle East is on the frontline in the challenge to control a potential public health crisis.Consequently,the countries of the Middle East should be encouraged to improve their health and research capacities to mitigate the threat posed by MBDs.

Biosafety and biosecurity in the Iraqi Kurdistan Region:Challenges and necessities

Dear Dr.Jianguo Xu,The recent COVID-19 pandemic has markedly increased our awareness of the inherent dangers in managing infectious agents like SARS-CoV-2 and highlighted the crucial need to improve laboratory facilities,equipment,and training for technicians to reduce the risks associated with handling these agents.The imperative to evolve laboratory designs and adopt stringent safety guidelines in medical labs and scientific institutions has become pressing.In particular,the advent of SARS-CoV-2 as a global threat has catapulted the need for robust biosecurity measures into the forefront of scientific discourse.The potential for unintentional biological outbreaks and the malicious exploitation of biological agents by terrorist organizations have intensified the research focus on biosafety by underlining the urgent need to strengthen biosafety and biosecurity measures in laboratories.1 This letter aims to explore the biosafety and biosecurity challenges encountered within the Iraqi Kurdistan region.

Kalman filter based on a fractional discrete-time stochastic augmented CoVid-19 model

In this paper,we study the dynamics of the CoVid-19 outbreak in Semarang,Indonesia,using a fractional CoVid-19 model.We first determine the effects of the isolation rateand infection rate b on the reproduction number R0 and infected number V.We find that R0 is directly proportional to b and inversely proportional to.For V,the effect of physical distancing is not as significant as changing.Asincreases,V decreases,the number of susceptible individuals increases,the number of quarantined individuals decreases sharply,and the number of recovered individuals decreases.Moreover,the effect of vaccination is also considered.The combination of physical distancing,isolation,and vaccination has a significant impact on reducing the number of infected individuals.Analysis of dynamical systems allows us to understand the characteristics of our model,such as its boundedness and non-negativity,the existence of equilibrium points,the existence and uniqueness of solutions,and the local and global stability.To validate our fractional CoVid-19 model,we introduce the fractional extended Kalman filter(FracEKF)as a prediction method and compare the results against reported CoVid-19 data.FracEKF is a modified version of the basic extended Kalman filter with a time-fractional memory effect.The prediction results illustrate the accuracy of this model in terms of the root mean square error(RMSE),normalized root mean square error(NRMSE),and mean absolute percentage error(MAPE)for each fractional-order.Varyingreproduces the trends observed in the reported data for the number of infected individuals,i.e.,whenincreases,the infected number decreases.Moreover,a higher fractional-order results in higher model accuracy.Furthermore,higher values of the process noise Qf give smaller errors,whereas higher values of the observation noise Rf produce higher errors.Qf and the fractional-order a are inversely proportional to RMSE;NRMSE,and MAPE,whereas Rf is directly proportional to RMSE;NRMSE,and MAPE.

United Nations side event on the Biological Weapons Convention by Tianjin University and City,University of London

On December 13th,2023,Tianjin University and City,University of London,jointly hosted a United Nations side event titled“Advancing from‘Tianjin Guideline on Behavior of Scientists in Biosafety’to‘International Biological Safety Education Network(IBSEN)”at the Palais des Nations in Geneva,Switzerland.This event marked the completion of the first edition of the international biosafety textbook,titled“Essentials of Biological Security,”initiated by the event organizers.International scientists collaborated on this textbook with the goal of establishing an international education network on biosafety on the basis of the Tianjin Guideline.

Legal framework for the sharing of pathogens:Issues and recommendations

The sharing of pathogens is of great significance for the continuous and comprehensive testing and monitoring of viral samples,vaccine and drug development,and the study of drug resistance and mutability of viral samples.This paper reviews the current legal framework in the field of pathogen sharing,analyzes existing issues,and proposes recommendations to improve the legal framework of pathogen sharing.