Population Coverage Research Articles

NERVE 2.0: boosting the new enhanced reverse vaccinology environment via artificial intelligence and a user-friendly web interface

BackgroundVaccines development in this millennium started by the milestone work on Neisseriameningitidis B, reporting the invention of Reverse Vaccinology (RV), which allows to identify vaccine candidates (VCs) by screening bacterial pathogens genome or proteome through computational analyses. When NERVE (New Enhanced RV Environment), the first RV software integrating tools to perform the selection of VCs, was released, it prompted further development in the field. However, the problem-solving potential of most, if not all, RV programs is still largely unexploited by experimental vaccinologists that impaired by somehow difficult interfaces, requiring bioinformatic skills. ResultsWe report here on the development and release of NERVE 2.0 (available at: https://nerve-bio.org) which keeps the original integrative and modular approach of NERVE, while showing higher predictive performance than its previous version and other web-RV programs (Vaxign and Vaxijen). We renewed some of its modules and added innovative ones, such as Loop-Razor, to recover fragments of promising vaccine candidates or Epitope Prediction for the epitope prediction binding affinities and population coverage. Along with two newly built AI (Artificial Intelligence)-based models: ESPAAN and Virulent. To improve user-friendliness, NERVE was shifted to a tutored, web-based interface, with a noSQL-database to consent the user to submit, obtain and retrieve analysis results at any moment.ConclusionsWith its redesigned and updated environment, NERVE 2.0 allows customisable and refinable bacterial protein vaccine analyses to all different kinds of users.

Beyond prevention: in silico designing a one-two punch novel therapeutic vaccine candidate against major oncoproteins of HPV 16, 18, 31, and 45 and subsequent cervical cancer

ABSTRACT The human papillomavirus (HPV) is the most prevalent viral sexually transmitted disease (STD). HPV 16, 18, 31 and 45 are most associated with the development of cervical cancer. Currently approved HPV vaccines are only preventive and have no therapeutic activity. With immunoinformatics approaches, we tried to design a novel vaccine against E6 and E7 oncoproteins of HPV 16, 18, 31 and 45 for the prevention and treatment of cervical cancer. The tertiary structure of the vaccine was modelled and validated. The vaccine was docked with TLR4 and TLR9 receptors, which have an undeniable anti-tumour immunity against cervical cancer. Molecular dynamic simulation indicates that the vaccine-TLR complexes were structurally stable. Immune stimulation and population coverage analysis results were much better than similar studies. Our new multi-epitope vaccine is the first HPV vaccine to target the E6 and E7 antigens of HPV 16, 18, 31 and 45. Also, this is the first study to target conserved regions of HPV and then merge the T and B cell epitopes as a regional epitope, which increases vaccine efficacy and reliability. We hope that the methodology of this study will even shed light on the design of vaccines against other viral STDs.

Novel affibody molecules targeting the AXL extracellular structural domain for molecular imaging and targeted therapy of gastric cancer.

Gastric cancer (GC) has a poor prognosis and high mortality because it is often diagnosed at an advanced stage. Targeted therapeutics are considered an important class for advanced GC treatment. However, the fewer effective therapeutic targets and the poor coverage of the GC population limit the use of GC targeted therapies. Recent research suggests that the AXL receptor tyrosine kinase (AXL) plays an vital role in the survival and proliferation of GC cells, and blocking AXL pathway may be an effective strategy for targeted therapies. On the other hand, the affibody molecule, with its small size and faster penetration of tissue, has great potential in tumor imaging and targeted therapy. In this study, we report the novel AXL-binding affibody molecules (ZAXL:239) screened by a phage-displayed peptide library. The ZAXL:239 could specifically bind and interact with AXL proteins in vitro and in vivo, as demonstrated by surface plasmon resonance, co-immunoprecipitation, immuno-fluorescence co-localization, and nearinfrared fluorescent imaging. In addition, ZAXL:239 affibody molecules could significantly inhibit the proliferative activity and induce apoptosis of AXL-positive GC cells by decreasing the phosphorylation levels of the PI3K/AKT1 and MEK/ERK pathway, leading to the suppression of the downstream nuclear protein c-myc. Moreover, ZAXL:239 was found to have significant anti-tumor effects in AXL-positive GC transplantation tumor nude mouse models. In brief, we provide strong evidence that the novel ZAXL:239 affibody molecules have great potential as a potent tumor-specific molecular imaging and targeted therapeutic agents for GC.

Design of multi-epitope-based therapeutic vaccine candidates from HBc and HBx proteins of hepatitis B virus using reverse vaccinology and immunoinformatics approaches.

The major problem in cases of chronic hepatitis B (CHB) is the failure of the patient's immune response to eliminate the covalently closed circular DNA (cccDNA) minichromosome of hepatitis B virus (HBV). Epigenetic regulation involving the HBV core protein (HBc) and HBV X protein (HBx) influences the transcription and stability of the cccDNA minichromosome. The HBc and/or HBx-based therapeutic vaccines that have been developed cannot accommodate differences between HBV genotypes. This research aims to design a therapeutic vaccine candidate based on the multi-epitope of HBc and HBx using reverse vaccinology (RV) and immunoinformatics approach. HBc and HBx sequences from 10 HBV genotypes were obtained from the NCBI Entrez Protein database. Epitopes were predicted from consensus sequences, which consisted of 13,610 HBc sequences and 12,333 HBx sequences. The study identified four cytotoxic T lymphocyte epitopes, two helper T lymphocyte epitopes, and five linear B lymphocyte that met the inclusion criteria. The vaccine candidate designed using cholera toxin subunit B and pan HLA DR-binding epitope adjuvants was predicted to be safe, antigenic, stable, and has a global population coverage of 99.43%. Molecular docking and molecular dynamics simulations demonstrated that the vaccine candidate could stably bind to B cell receptor, cytotoxic T cell receptor, and TLR4 for 100 ns. Immune response simulation indicated that it can induce antibody production and the proliferation of B and T cells. It can be concluded that RV and immunoinformatics successfully facilitated the design of a multi-epitope therapeutic vaccine candidate for CHB.

The Assessment of Knowledge About Cervical Cancer, HPV Vaccinations, and Screening Programs Among Women as an Element of Cervical Cancer Prevention in Poland

Introduction: Cervical cancer is the fourth most commonly diagnosed malignant tumor in women and the fourth leading cause of cancer-related deaths among this population. Since it is asymptomatic in its early stages, preventive screening plays a crucial role in rapid diagnosis. Such screenings are conducted in many countries worldwide, although their popularity varies. Given that nearly all cases of cervical cancer are linked to high-risk human papillomavirus (hrHPV) infection, vaccination against this virus could lead to a significant reduction in cancer incidence. It should be noted that the level of vaccination coverage against hrHPV varies significantly between countries, ranging from a few percent to over 90%. Globally, the vaccination coverage of the target population is estimated at only a few percent. Methods: This study was conducted using a proprietary, anonymous online questionnaire comprising 24 questions addressing various aspects of cervical cancer prevention. The newly designed questionnaire comprised 19 primary questions and 5 metric questions. The collected data were subjected to descriptive and statistical analysis. Results: The majority of respondents reported regularly participating in cervical cytology screening and gynecological visits. Non-participation in these screenings was primarily reported by younger respondents, not all of whom had indications for undergoing such examinations. Only 14% of the women surveyed had been vaccinated against hrHPV. However, it should be noted that, as the surveyed women were not covered by the relatively recently introduced vaccination program, they received their vaccinations through local programs conducted by certain cities or through private healthcare services. The respondents’ primary sources of information on cervical cancer are the internet and medical personnel. Conclusions: The level of knowledge among the women surveyed regarding cervical cancer prevention was satisfactory, though improvement is needed in some areas. Despite relatively good awareness of HPV’s role in cervical cancer development, the popularity of HPV vaccination remains unsatisfactory. The results should be interpreted with caution due to the small study group.

From bytes to bites: In-silico creation of a novel multi-epitope vaccine against Murray Valley Encephalitis Virus

Flaviviruses transmitted by arthropods, including the Murray Valley Encephalitis Virus (MVEV), are RNA viruses capable of causing severe encephalitis in various hosts. The spread of these viruses is closely linked to climatic conditions and the habitats of host and vector species, leading to outbreaks in new geographic regions. Notable encephalitis-causing flaviviruses include Japanese encephalitis virus (JEV), West Nile virus (WNV), and Kunjin virus (KUNV). MVEV, primarily spread by the mosquito Culex annulirostris and amplified by water birds such as egrets and Nankeen night herons, has caused significant outbreaks in Australia, including severe epidemics in 1951, 1956, and 1974. Despite its severity, no rapid diagnostic techniques or effective antiviral treatments are available, and current interventions are limited to supportive care and mosquito management. Given the absence of a licensed vaccine, this study aimed to develop a multi-epitope hybrid vaccine targeting MVEV using in silico approaches. The study focused on identifying B-cell and T-cell epitopes from the MVEV Envelope (E) protein, constructing a vaccine candidate, and computationally validating its immunogenic potential. The designed vaccine underwent rigorous analysis of its antigenic properties, allergenicity, and toxicity. Disulfide engineering and assessment of physicochemical properties ensured the structural integrity of the vaccine, supported by Ramachandran plot and ProSA web analyses. Molecular docking studies assessed the vaccine's binding affinities with TLR-3, and MHC-I. Population coverage analysis of MHC-I and MHC-II epitopes evaluated global efficacy. Additionally, molecular dynamics simulations explored the stability of docked complexes, and PDBsum analysis elucidated interaction details. Immunological simulations were conducted to predict immune response outcomes, providing comprehensive validation of the vaccine's antigenicity. The findings highlight the potential of a multi-epitope vaccine as a viable strategy for MVEV prevention.

Multi-objective allocation of COVID-19 testing centers: improving coverage and equity in access

At the time of this article, COVID-19 has been transmitted to more than 42 million people and resulted in more than 673,000 deaths across the United States. Throughout this pandemic, public health authorities have monitored the results of diagnostic testing to identify hotspots of transmission. Such information can help reduce or block transmission paths of COVID-19 and help infected patients receive early treatment. However, most current schemes of test site allocation have been based on experience or convenience, often resulting in low efficiency and non-optimal allocation (as suggested by our case study results). In addition, the historical sociodemographic patterns of populations within cities can result in measurable inequities in access to testing between various racial and income groups. To address these pressing issues, we propose a novel test site allocation scheme to (a) maximize population coverage, (b) minimize prediction uncertainties associated with projections of outbreak trajectories, and (c) reduce inequities in access to testing. We illustrate our approach with case studies comparing our allocation scheme with recorded allocation of testing sites in the state of Georgia, USA revealing increases in both population coverage and improvements in equity of access over current practice.

Analysis of the incidence of influenza and acute upper respiratory tract infections under conditions of routine influenza vaccination

Background. Acute upper respiratory tract infections and influenza, while maintaining high epidemiological, social and economic significance, have a major effect on the public health of countries and individual regions.The aim. To study the impact of influenza vaccination on the manifestations of the epidemic process of influenza and acute upper respiratory tract infections in the Irkutsk region.Materials and methods. Epidemiological analysis of the incidence of acute upper respiratory tract infections and influenza, analysis of influenza mortality and the impact of vaccination on these infections were performed using continuous samples of statistical data from the Directorate of Rospotrebnadzor in the Irkutsk Region for the period of 2003–2022 (forms 2, 5).Results. The intensity of the epidemic process of acute upper respiratory tract infections among the general population, children and adults during the observation period was characterized by an uneven course with a tendency towards increase. The dynamics of the incidence of acute upper respiratory tract infections in children and adults demonstrates multidirectional trends over the compared periods. The incidence of influenza in the general population had a steady downward trend, the decrease rate was –8.4 %. At the same time, there are significant changes in the intensity of the epidemic process in the compared periods. The proportion of adults increased in the structure of cases of acute upper respiratory tract infections, and the proportion of children increased in the structure of cases of influenza. Significant changes in the epidemic seasons of influenza are shown. Since the beginning of routine influenza vaccination in the region, the number of vaccinated people has increased annually – from 23.6 to 61.7 % of the population. Against the background of the influenza vaccination campaign, a statistically significant decrease in the incidence of acute upper respiratory tract infections among the general population and children under 14 years of age was registered (p < 0.01).Conclusion. In the Irkutsk region, the epidemiological disadvantage for the studied infections persists. Increasing the regulated indicators of population coverage with preventive influenza vaccinations (75 % and more) will help reduce the incidence rate.

An evaluation of the impact of a national Minimum Unit Price on alcohol policy on alcohol behaviours.

In 2018, Scotland pioneered national legislation which set a Minimum Unit Price (MUP) of 50 pence (∼US$0.64, €0.59) per unit of UK alcohol sold (8g/10ml). To inform policy development, we examine the policy effect using the Alcohol Use Disorders Identification Test (AUDIT-C), employing longitudinal data for over 17200 individuals. The effect of MUP on AUDIT-C scores is inferred by employing difference-in-difference regression. Pre- and post-intervention alcohol behaviours of individuals from Scotland are compared to a matched 'control' from England. Drinking at hazardous and harmful levels could be identified, as well as the frequency of alcohol consumption, number of drinks and heavy episodic drinking. Estimates adjust for demographic, socioeconomic and health characteristics. Potential inequalities by gender, age and household income are examined. MUP led to an estimated 5.3% reduction in the number of drinks consumed on drinking occasions, though a statistically significant effect on overall reported AUDIT-C scores or drinking at hazardous levels was not detected, with few differential effects for subgroups. Differences in the findings of this research compared to other studies may be explained by differences in population coverage collected in the survey data, compared to more comprehensive, population-wide administrative data, as well as sample attrition.

Healthcare inequity arising from unequal response to need in the older (45+ years) population of India: Analysis of nationally representative data

Given the large and growing number of older (45+ years) people in India, inequitable access to healthcare in this population would slow global progress toward universal health coverage. We used a 2017-18 nationally representative sample of this population (n = 53,687) to estimate healthcare inequality and inequity by economic status. We used an extensive battery of indicators in nine health domains, plus age and sex, to adjust for need. We measured economic status by monthly per capita consumption expenditure and used a concentration index to measure inequalities in probabilities of any doctor visit and any hospitalisation within 12 months. We decomposed inequality with a regression method that allowed for economic and urban/rural heterogeneity in partial associations between healthcare and both need and non-need covariates. We used the associations achieved by the richest fifth of urban dwellers to predict a need-justified distribution of healthcare and compared the actual distribution with that benchmark to identify inequity. We found pro-rich inequalities in doctor visits and hospitalisations, which were driven by use of private healthcare. Adjustment for the greater need of poorer individuals revealed pro-rich inequity that exceeded inequality by about 65% and 39% for doctor visits and hospitalisations, respectively. These adjustments would have been substantially smaller, and inequity underestimated, without allowing for use-need heterogeneity, which accounted for 11% of the inequity in doctor visits and was 373% of inequity in hospitalisations. Targeting service coverage on poorer and rural groups, and increasing their access to private providers, would both reduce inequity and raise average coverage in the older population of India.

Enhancing geographical access to cardiovascular disease healthcare services in Lagos State, Nigeria

Abstract Cardiovascular diseases (CVDs) are the leading cause of global mortality, and three-quarters of the world’s deaths from CVDs occur in low- and middle-income countries. Improving spatial access to care facilities is a way of reducing the disease burden through early detection and treatment. Determining the number of facilities to provide and the locations in order to improve accessibility is central to healthcare facility planning. The maximal covering location problem (MCLP) was used in the identification and determination of where to place additional CVD treatment facilities in Lagos State for better accessibility. The primary objective of this study was to optimize the placement of CVD facilities to maximize coverage for both patients and non-patients alike. The optimization model utilized data on the population of Lagos State, the locations of CVD patients, the location of existing CVD care facilities, and the locations of general hospitals (GHs) within the state. The MCLP implementation was carried out using the maxcovr. The results of the models indicated that the addition of two facilities at the Isolo and Ile-Epo GHs would enhance CVD patient coverage from 70 to 87.4%, reducing the average travel distance from 9,038 to 6,466 m. Similarly, the introduction of two facilities at the Ikorodu and Ajegunle GHs improved population coverage from 40.3 to 70.8%, reducing the average travel distance of 18,788 m by over 5,000 m. These findings are expected to offer valuable insights for public health decision-makers who face the challenge of prioritizing limited budgets.

Treatment-related characteristics of communities in districts characterized by persistent trachoma: an exploratory descriptive study

Abstract Background Despite the implementation of surgery, antibiotics mass administration, facial cleanliness and environmental improvement, commonly known as the SAFE strategy for several years, the persistence and recrudescence of trachoma is a prevailing challenge in Ethiopia. This study explores the treatment-related characteristics of communities within districts characterized by persistent trachoma in southern Ethiopia. Methods Nyangatom and Uba Debretsehay districts are predominantly inhabited by pastoralist and farming communities, respectively. A community-based, exploratory descriptive qualitative study was conducted from June to October 2023. A total of 11 key informant interviews and six focus group discussions were conducted. The interviews and discussions were digitally recorded, transcribed and thematically analysed using Atlas ti. 23. Results Districts characterized by persistent trachoma are characterized by segments of populations that have never been treated or suboptimally treated. This is due to the competing priorities faced by providers, the nature of campaigns and the limited ability of logistics to reach the ‘must reach’ population. Other barriers include limited social support and terrain hindering full geographical and population coverage. Treatment slippage is of particular concern because of treatment fatigue, misinformation and the unavailability of treatments for routine care. Conclusions Communities in districts characterized by persistent and recrudescent trachoma face various socioecological barriers that impact the outcome of SAFE strategy implementation. A mix of both random and systematic omissions of people who need treatment most, such as children and women, was evident.

Exploring Park and Ride: A Spatial Analysis of Transit Catchment in Outer Melbourne

Public transportation is essential for improving urban mobility, enhancing travel quality, reducing reliance on private vehicles, and alleviating traffic congestion. However, inadequate public transportation in outer Melbourne is a significant issue limiting urban development. While existing research primarily focuses on walking distance to define service catchments, commuters in transit-disadvantaged or outlying urban areas often drive to transit, noted as the park-and-ride mode. This research uniquely examines drive-distance catchments for park-and-ride transit accessibility in outer Melbourne, using spatial SQL and GIS techniques to provide a detailed, multi-dimensional analysis of population coverage, parking capacity, and accessibility gaps. This approach fills a gap in the existing literature by offering adaptable insights and approaches to other outer urban areas with transit disadvantages. The findings underscore the necessity for targeted enhancements in public transportation in outer Melbourne: Most of the outer residents concentrate near the train stations, though significant spatial gaps exist; The general accessibility status of residential mesh blocks is found; Parking capacity varies with high tension found at certain stations. This study contributes insights to create more equitable and sustainable transportation systems by providing a detailed spatial analysis of current transit coverage and identifying critical gaps.

Multimodal Biometric Authentication System for Military Weapon Access: Face and ECG Authentication

Unimodal or Single factor biometric systems refer to biometric systems that employ only one form of biometric data to authenticate an individual’s identity. These kinds of biometrics are susceptible to higher error rates and security vulnerabilities because it relays on a single trait for authentication. To overcome this, multimodal biometrics method is proposed. Multi-modal biometric system can authenticate more than once and some advantages include; highaccuracy, low error rate, and large population coverage. These biometrics systems increase integrity and privacy since it will contain several biometric features of every customer. So, here designed a multimodal biometrics project utilizing deep learning to enhance authentication security by combining face and Electrocardiogram(ECG) signals. VGG-16 model, a deep learning architecture used to capture complex patterns in accurate individual identification with both ECG and Facial data. The high-resolution convolutional filters capture the intricate details of the face and ECG waveform, ensuring high accuracy in distinguishing different individuals.

PharmFreq: a comprehensive atlas of ethnogeographic allelic variation in clinically important pharmacogenes.

Genetic polymorphisms in drug metabolizing enzymes, drug transporters as well as in genes encoding the human major histocompatibility complex contribute to inter-individual differences in drug efficacy and safety. The extent, pattern and complexity of such pharmacogenetic variation differ drastically across human populations. Here, we present PharmFreq, a global repository of pharmacogenetic frequency information that aggregates frequency data of 658 allelic variants from over 10 million individuals collected from>1200 studies across 144 countries. Most investigations were conducted in East Asian and European populations, accounting for 29.4 and 26.6% of all studies, respectively. We find that the number of studies per country and aggregated cohort size correlated significantly with population size (R=0.55, P=3*10-9) and country gross domestic product (R=0.43, P=2*10-6) with overall population coverage varying between 5% in Estonia to<0.001% in many countries in Sub-Saharan Africa and Asia. All frequency data are openly accessible via a web-based interactive dashboard at pharmfreq.com that facilitates the exploration, visualization and analysis of country- and population-specific data and their inferred phenotypic consequences. PharmFreq thus presents a comprehensive, freely available resource for pharmacogenetic variant frequencies that can inform about ethnogeographic pharmacogenomic diversity and reveal important inequities that help to focus future research efforts into underrepresented populations.

Abstract 4135352: Neighborhood-level Determinants and Disparities in Incident Type 2 Diabetes in a Population-Based Cohort, 2015–2020

Introduction: Living in an area with high Area Deprivation Index (ADI) is linked to worse cardiovascular disease (CVD) outcomes. However, the association of ADI with type 2 diabetes (T2D), a major CVD risk factor, is incompletely described. This knowledge may guide primary CVD prevention. Method: Rochester Epidemiology Project is a medical record linkage system of persons in southeast Minnesota and southwest Wisconsin. We identified 253,890 persons (aged 4–98 yrs on July 1, 2015) in 9 counties with &gt;90% population coverage. ADI scores, from 2015 home addresses, were grouped into quartiles of low (Q1) to high (Q4) deprivation. We excluded persons with type 1 diabetes (T1D) or history of T2D and identified new T2D cases (2015-2020) using ICD codes, HbA1c and medications. We examined the association between ADI quartile and risk of incident T2D using Cox regression with persons right censored at death, T2D, T1D or last visit. Models were adjusted for age and gender, and reported adjusted hazard ratios (aHR [95% confidence interval]). Results: Age, gender, and race statistically differed across ADI quartiles (Table). Age × ADI interaction was significant ( P &lt;.001). T2D incidence ranged from 6.3 (Q1) to 9.0 (Q4) per 1000 person-years ( P &lt;.001). Women vs. men/non-binary persons (combined due to limited non-binary persons) had 30% lower risk of incident T2D (aHR 0.70 [0.67–0.72]). Risk of incident T2D was higher in persons from higher ADI areas. At median age of 48.6 yrs, the risk was 30% higher in Q2 (aHR 1.3 [1.22–1.38]), 38% higher in Q3 (aHR 1.38 [1.30–1.47]) and 53% higher in Q4 (aHR 1.53 [1.43–1.62]) vs. Q1. Higher ADI was associated with higher incident T2D in younger persons, with risk attenuation with increasing age (Figure). Conclusion: In this population cohort, persons, particularly of younger age, living in more deprived areas had a higher risk of incident T2D. ADI may help identify areas for targeted T2D screening, with implications for CVD screening and prevention.

Incidence and risk factors of congenital heart disease in Qingdao

Objective: To analyze the incidence and risk factors of congenital heart disease (CHD) in Qingdao. Methods: A prospective study was adapted, and study participants were pregnant women who underwent prenatal screening in Qingdao from August 2018 to June 2020 and their offspring (the whole population coverage). CHD in neonates was screened by using the pulse oximetry saturation and heart auscultation, and the final diagnosis was determined by the result of echocardiography. Multivariable logistic regression was performed to analyze the risk factors of CHD. Results: The study included 115 238 live births, among which 709 were diagnosed with CHD, with an incidence of 6.15/1 000. Ventricular septal defect, atrial septal defect, as well as ventricular septal defect and atrial septal defect were the main CHD subtypes, with incidences of 2.97/1 000 (342/115 238), 1.01/1 000 (116/115 238), and 0.39/1 000 (45/115 238), respectively, comprising 48.2% (342/709), 16.4% (116/709), and 6.3% (45/709) of the CHD cases. The results of multivariable logistic regression showed that the offspring of women with a graduate degree (compared to junior high school or below) (OR=1.66, 95%CI: 1.15-2.40), pregnancy history of CHD (OR=9.50, 95%CI: 5.37-16.81), pregestational diabetes mellitus (OR=3.40, 95%CI: 1.58-7.32) had a higher risk of having CHD, whereas the offspring of multiparous women was associated with a lower risk of CHD (OR=0.84, 95%CI: 0.71-0.99). In addition, compared with male newborns, female newborns have a higher risk of having CHD (OR=1.18, 95%CI: 1.01-1.39). Conclusions: The incidence of CHD in Qingdao is 6.15/1 000, with ventricular septal defect, atrial septal defect, as well as ventricular septal defect and atrial septal defect being the main subtypes. Maternal education, parity, pregnancy history of CHD, pregestational diabetes mellitus, and offspring gender are associated with CHD occurrence.

Cancer Risk Among Patients With Multiple Sclerosis: A 10-Year Nationwide Retrospective Cohort Study.

Previous literature has been diverging on cancer risk in people with multiple sclerosis (PwMS). Therefore, this study compared the risk of cancer in PwMS and a matched sample from the French general population. This 10-year nationwide retrospective matched cohort study (2012-2021) used data from the national French administrative health care database (99% coverage of the French population) to determine the time to the first incident cancer. PwMS were identified using their long-term disease (LTD) status, hospitalizations, and multiple sclerosis (MS)-specific drug reimbursements. The control population was matched 4:1 on age, sex, residence, insurance scheme, and cohort entry date. Participants were included if they had no history of cancer in the 3 years before inclusion. Patients with cancer were identified through LTD status, hospitalizations, chemotherapy, radiotherapy, or prostate cancer-specific drug reimbursements. Overall and cancer location-specific hazard ratios (HRs) for the first incident cancer were obtained from Fine and Gray models, and age- and sex-stratified estimates were reported. Participation in cancer screening through the 3 national programs (breast, colorectal, and cervical) were compared between groups. Cancer incidence was 799 per 100,000 person-years (PYs) (n = 8,368) among the 140,649 PwMS and 736 per 100,000 PYs (n = 31,796) among the 562,596 matched controls (70.8% of women; follow-up: 7.6 ± 3.2 years). A small overall risk increase was observed for PwMS (HR 1.06, 95% CI 1.03-1.08), mostly in women (HR 1.08, 95% CI 1.05-1.11). Risk varied by cancer types and was lower for prostate (HR 0.80, 95% CI 0.73-0.88), breast (HR 0.91, 95% CI 0.86-0.95), and colorectal (HR 0.90, 95% CI 0.84-0.97) cancer and higher for bladder (HR 1.71, 95% CI 1.54-1.89), brain (HR 1.68, 95% CI 1.42-1.98), and cervical (HR 1.24, 95% CI 1.12-1.38) cancer in PwMS. Cancer risk was higher in PwMS younger than 55 years (HR 1.20, 95% CI 1.15-1.24) but decreased in PwMS aged 65 years and older (HR 0.89, 95% CI 0.85-0.94). This trend was found in all cancer locations. There were fewer PwMS getting screened than controls (all programs), with a particularly pronounced difference among those aged 65 years and older. Cancer risk was slightly increased in PwMS, particularly for urogenital cancers, possibly due to surveillance bias. Risk fluctuated depending on age, perhaps due to varying generational screening practices (i.e., diagnosis neglect in the older PwMS) and risk factors.

Optimizing spatial distribution of wastewater-based epidemiology to advance health equity

In 2022, the US Centers for Disease Control and Prevention commissioned the National Academies of Sciences, Engineering, and Medicine to assess the role of community-level wastewater-based epidemiology (WBE) beyond COVID-19. WBE is recognized as a promising mechanism for promptly identifying infectious diseases, including COVID-19 and other novel pathogens. An important conclusion from this initiative is the critical importance of maintaining equity and expanding access to fully realize the benefits of wastewater surveillance for marginalized communities. To address this need, we propose an optimization framework that strategically allocates wastewater monitoring resources at the wastewater treatment plant (WWTP) level, ensuring more effective and equitable distribution of surveillance efforts to serve underserved populations.The purpose of the framework is to obtain a balanced spatial distribution, inclusive population coverage, and efficient representation of disadvantaged groups in the allocation of resources for WBE. Furthermore, the framework concentrates on areas with high population density and gives priority to vulnerable regions, as well as identifying signals that display significant variations from other monitored sources. The optimization objective is to maximize a weighted combination of these critical factors. This problem is formulated as an integer optimization problem and solved using simulated annealing. We evaluate various scenarios, considering different weighting factors, to optimize the allocation of WWTPs with monitoring systems. This optimization framework provides an opportunity to enhance WBE by providing customized monitoring strategies created to address specific priorities and situations, thus enhancing the decision-making processes in public health responses.

Developing a chimeric multiepitope vaccine against Nipah virus (NiV) through immunoinformatics, molecular docking and dynamic simulation approaches

Nipah virus (NiV) is a highly lethal zoonotic pathogen that poses a significant threat to human and animal health. Unfortunately, no effective treatments have been developed for this deadly zoonotic disease. Therefore, we designed a chimeric multiepitope vaccine targeting the Nipah virus (NiV) glycoprotein and fusion protein through immunoinformatic approaches. Therefore, the vaccine was developed by combining promising and potential antigenic MHC-I, MHC-II, and B-cell epitopes obtained from the selected proteins. When combined, the MHC-I and MHC-II epitopes offered 100 % global population coverage. The physicochemical characterization also exhibited favorable properties, including solubility and potential functional stability of the vaccine within the body (GRAVY score of −0.308). Structural analyses unveiled a well-stabilized secondary and tertiary structure with a Ramachandran score of 84.4 % and a Z score of −5.02. Findings from docking experiments with TLR-2 (−1089.3 kJ/mol) and TLR-4 (−1016.7 kJ/mol) showed a strong affinity of the vaccine towards the receptor. Molecular dynamics simulations revealed unique conformational dynamics among the “vaccine-apo,” “vaccine-TLR-2,” and “vaccine-TLR-4″ complexes. Consequently, the complexes exhibited significant compactness, flexibility, and exposure to solvents. The results of the codon optimization were remarkable, as the vaccine showed a significant amount of expression in the E. coli vector (GC content of 45.36 % and a CAI score of 1.0). The results of immune simulations, however, showed evidence of both adaptive and innate immune responses induced by the vaccine. Therefore, we highly recommend further research on this chimeric multiepitope vaccine to establish its efficacy and safety against the Nipah virus (NiV).