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The vaccine, a distinctive product with specific characteristics, plays a crucial role in enhancing human immunity against diseases for their eradication. Given the severe impact of the COVID-19 pandemic on humanity, numerous challenges lie ahead, underscoring the necessity to develop and enhance medical, economic, and managerial components of vaccine development, as well as to integrate digital technologies and coordinate all stakeholders to respond effectively to the epidemic. All of these considerations refer to the need for a vaccine lifecycle management approach. Despite existing literature, many studies focus on isolated stages, neglecting the essential holistic view required to understand interconnections and the overall impact of proposed solutions on the whole lifecycle. This study addresses this research gap, by systematically tackling major challenges throughout the vaccine lifecycle. Our research contributes to the literature by (a) providing a systematic examination of the literature surrounding Vaccine Lifecycle Management, offering insights into the existing challenges and issues faced in the various stages of vaccine development, production, distribution, and administration, and (b) proposing recommendations or directions for improvement in managing the entire lifecycle of vaccines. Our results could be valuable perspectives for decision-makers involved in the process. [ABSTRACT FROM AUTHOR]

BACKGROUND: Artemisinin resistance in Plasmodium falciparum threatens global malaria elimination efforts. To contain and then eliminate artemisinin resistance in Eastern Myanmar a network of community-based malaria posts was instituted and targeted mass drug administration (MDA) with dihydroartemisinin-piperaquine (three rounds at monthly intervals) was conducted. The prevalence of artemisinin resistance during the elimination campaign (2013-2019) was characterized. METHODS: Throughout the six-year campaign Plasmodium falciparum positive blood samples from symptomatic patients and from cross-sectional surveys were genotyped for mutations in kelch-13-a molecular marker of artemisinin resistance. RESULT: The program resulted in near elimination of falciparum malaria. Of 5162 P. falciparum positive blood samples genotyped, 3281 (63.6%) had K13 mutations. The prevalence of K13 mutations was 73.9% in 2013 and 64.4% in 2019. Overall, there was a small but significant decline in the proportion of K13 mutants (p

BACKGROUND: In Madagascar, the districts of Antsirabe II, Faratsiho and Antsiranana I have relatively low malaria incidence rates and have been selected by the National Malaria Control Programme for pilot elimination strategies. The districts have residual transmission despite increasing coverage and quality of malaria services. This study sought to identify priority subpopulations at highest risk for malaria and collect information on intervention preferences and methods that will inform subnational tailoring of malaria service delivery. METHODS: This mixed methods study employed (i) a quantitative malaria risk factor assessment in Antsirabe II and Faratsiho comprising a test-negative frequency matched case-control study and a qualitative risk factor assessment in Antsiranana I; and (ii) a qualitative formative assessment in all three districts. For the case-control study, a mixed effects logistic regression was used with age, sex and district included as fixed effects and health facility included as a random effect. The qualitative risk factor assessment used semi-structured interview guides and key informant interviews. For the qualitative formative assessment in the three districts, a summary report was generated following semi-structured interviews and focus group discussions with high-risk populations (HRPs) and stakeholders. RESULTS: In Antsirabe II and Faratsiho districts, rice agriculture workers, outdoor/manual workers, particularly miners, and those with jobs that required travel or overnight stays, especially itinerant vendors, had higher odds of malaria infection compared to other (non-rice) agricultural workers. In Antsiranana I, respondents identified non-rice farmers, mobile vendors, and students as HRPs. Risk factors among these groups included overnight stays and travel patterns combined with a lack of malaria prevention tools. HRPs reported treatment cost and distance to the health facility as barriers to care and expressed interest in presumptive treatment and involvement of gatekeepers or people who have influence over intervention access or participation. CONCLUSIONS: The study results illustrate the value of in-depth assessments of risk behaviours, access to services and prevention tools, surveillance and prevention strategies, and the involvement of gatekeepers in shaping subnational tailoring to reach previously unreached populations and address residual transmission in elimination settings.

Assessing the feasibility of 2030 as a target date for global elimination of trachoma, and identification of districts that may require enhanced treatment to meet World Health Organization (WHO) elimination criteria by this date are key challenges in operational planning for trachoma programmes. Here we address these challenges by prospectively evaluating forecasting models of trachomatous inflammation-follicular (TF) prevalence, leveraging ensemble-based approaches. Seven candidate probabilistic models were developed to forecast district-wise TF prevalence in 11 760 districts, trained using district-level data on the population prevalence of TF in children aged 1-9 years from 2004 to 2022. Geographical location, history of mass drug administration treatment, and previously measured prevalence data were included in these models as key predictors. The best-performing models were included in an ensemble, using weights derived from their relative likelihood scores. To incorporate the inherent stochasticity of disease transmission and challenges of population-level surveillance, we forecasted probability distributions for the TF prevalence in each geographic district, rather than predicting a single value. Based on our probabilistic forecasts, 1.46% (95% confidence interval [CI]: 1.43-1.48%) of all districts in trachoma-endemic countries, equivalent to 172 districts, will exceed the 5% TF control threshold in 2030 with the current interventions. Global elimination of trachoma as a public health problem by 2030 may require enhanced intervention and/or surveillance of high-risk districts.

A mathematical model is designed to investigate Tuberculosis (TB) disease under the vaccination, treatment, and environmental impact with real cases. First, we introduce the model formulation in non-integer order derivative and then, extend the model into fractional order derivative. The fractional system's existence, uniqueness, and other relevant properties are shown. Then, we study the stability analysis of the equilibrium points. The disease-free equilibrium (DFE) 0 is locally asymptotically stable (LAS) when ℛ v < 1. Further, we show the global asymptotical stability (GAS) of the endemic equilibrium (EE) ∗ for ℛ v > 1 and 0 for ℛ v ≤ 1. The existence of bifurcation analysis in the model is investigated, and it is shown the system possesses the forward bifurcation phenomenon. Sensitivity analysis has been performed to determine the sensitive parameters that impact ℛ v. We consider the real TB statistics from Khyber Pakhtunkhwa in Pakistan and parameterized the model. The computed basic reproduction number obtained using the real cases is ℛ 0 ≈ 3.6615. Various numerical results regarding disease elimination of the sensitive parameters are shown graphically. [ABSTRACT FROM AUTHOR]

Background: Soil-transmitted helminth (STH) infections can cause a significant disease burden. It is estimated that 1.5 billion people worldwide are infected with STHs, primarily in tropical and subtropical regions. This study aimed to assess the distribution of the global burden and trend of STH infections from 1990 to 2021. Methods: We retrieved data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 on the age-standardized rates (ASRs) of prevalence and disability-adjusted life-years (DALYs) of STH infections for all age groups in 204 countries and territories from 1990 to 2021. The ASRs of prevalence and DALYs by age, gender, and socio-demographic index (SDI) were calculated to quantify the spatial distribution and temporal trend. Spearman correlation analysis was used to examine the relationship between ASR and SDI. Results: In 2021, there were an estimated 642.72 million cases and 1.38 million DALYs caused by STH infections worldwide. The age-standardized prevalence rate (ASPR) of STH infections was 8429.89 [95% uncertainty interval (UI): 7697.23, 9362.18 ] per 100,000 population globally. The ASPR of STH infections varied across 21 geographic regions in 2021, being mainly prevalent in most African and Latin American locations. The prevalence was higher in the groups of 5–19 years, especially the group of 5–9 years with the ASPR of 16,263 (95% UI: 14,877.06, 18,003.49) and ASR of DALYs of 40.69 (95% UI: 25.98, 60.91) per 100,000. The ASPR of STH infections showed an obvious decreasing trend worldwide (estimated annual percent change = − 4.03, 95% confidence interval: − 4.13, − 3.93) with variations in different species infections during the study years. At the regional level, the ASR of STH infections prevalence (r = − 0.8807, P < 0.0001) and DALYs (r = − 0.9069, P < 0.0001) were negatively correlated with SDI. Conclusions: STH infections remain a public health problem in 2021, particularly in regions such as the middle parts of Africa and Americas, and in the 5–19 age populations. The reduction in the rate of prevalence and the loss of DALYs are negatively correlated with the increase in SDI. Enhancing political commitment, providing accurate preventive chemotherapy, and advancing techniques for surveillance and mapping systems are essential to achieve the target of ending STH infections as a public health problem by 2030. [ABSTRACT FROM AUTHOR]

Background A barrier to hepatitis C virus (HCV) cure is conventional testing. The aim of this study was to evaluate the effect of HCV antibody and RNA point-of-care testing (POCT) on testing rates, linkage to care, treatment, and acceptability of testing in 3 priority settings in Australia. Methods Participants were enrolled in an interventional cohort study at a reception prison, inpatient mental health service, and inpatient alcohol and other drug unit, between October 2020 and December 2021. HCV POCT was performed using SD Bioline HCV antibody fingerstick test and a reflexive Xpert HCV Viral Load Fingerstick test using capillary blood samples. A retrospective audit of HCV testing and treatment data was performed at each site for the preceding 12-month period to generate a historical control. Results A total of 1549 participants received a HCV antibody test with 17% (264 of 1549) receiving a positive result, of whom 21% (55 of 264) tested HCV RNA positive. Across all settings the rate of testing per year significantly increased between the historical controls and the study intervention period by 2.57 fold (rate ratio, 2.57 [95% confidence interval, 2.32–2.85]) for HCV antibody testing and 1.62 (rate ratio, 1.62 [95% confidence interval, 1.31–2.01]) for RNA testing. Treatment uptake was higher during the POCT intervention (86% [47 of 55]; P =.01) compared to the historical controls (61% [27 of 44]). Conclusions This study demonstrated across 3 settings that the use of HCV antibody and RNA POCT increased testing rates, treatment uptake, and linkage to care. The testing model was highly acceptable for most participants. Clinical Trials Registration ACTRN-12621001578897 [ABSTRACT FROM AUTHOR]

In an ecosystem, harvesting infected prey can assist in managing and containing the spread of the illness within the prey species. On the other hand, the harvesting of predators can be beneficial as it regulates their numbers, preventing them from over-consuming prey and subsequently preserving existence of the prey population. This study introduces a predator–prey model that encompasses prey infection, predator–prey interactions influenced by fear, switching and harvesting. We derive an analytic expression for the basic reproduction number, a critical determinant of disease spread. We investigate the global stability of disease-free and endemic equilibria contingent on the basic reproduction number’s value, highlighting the potential for disease eradication by maintaining it below unity. In-depth analysis of the deterministic model is undertaken, with a focus on Hopf bifurcations that delineate thresholds for disease-free and endemic states. Furthermore, the deterministic model is extended to incorporate environmental stochasticity. We obtain the conditions under which population extinction occurs. Our findings elucidate how the intensity of environmental noise influences population dynamics, providing valuable insights into extinction risks under varying noise levels. [ABSTRACT FROM AUTHOR]

This research conducts a comprehensive analytical investigation into a stochastic SIR epidemic model that integrates nonlinear power functions and logistic growth dynamics. We examine the intricacies of model behavior, demonstrating its capability to produce a positive global solution. Utilizing precisely defined Lyapunov functions, we demonstrate the essential prerequisites for establishing the ergodicity of this particular model. Furthermore, the research deduces adequate criteria for predicting the eventual eradication of infectious diseases within this theoretical framework. Ultimately, we supplement the study with numerical simulations to elucidate and substantiate the analytical findings. This work contributes to comprehending epidemic systems with nuanced growth patterns and intricate disease transmission mechanisms, offering insights into real-world epidemic potential behaviors and outcomes. [ABSTRACT FROM AUTHOR]

This study explores an epidemic model elucidating the dynamics of COVID-19 transmission amidst vaccination and saturated treatment interventions. The investigation encompasses both deterministic and stochastic frameworks, considering constant and fluctuating environments, utilizing COVID-19 data from India for empirical validation. Through rigorous mathematical and numerical analyses, we ascertain pivotal insights. Our deterministic model unveils a critical phenomenon: the occurrence of backward bifurcation at ℛ0 = 1, underscoring that merely reducing the basic reproduction number below unity does not ensure disease eradication. Sensitivity analyses underscore the acceleration of epidemic spread with higher transmission rates, yet mitigation measures such as vaccination and comprehensive treatment can effectively reduce the basic reproduction number below unity. Within the stochastic framework, we establish the existence of a unique global positive solution. We delineate conditions for disease extinction or persistence and identify criteria for the emergence of stationary distribution, reflecting the sustained presence of infection within the community. Our findings elucidate that while smaller noise intensities sustain disease prevalence, heightened noise levels lead to complete eradication of the infection. [ABSTRACT FROM AUTHOR]

Background The global incidence target for the elimination of hepatitis C among people who inject drugs (PWID) is <2/100. In Norway, the hepatitis C epidemic is concentrated in PWID. Immigrants are the second most important risk group for chronic infection. We modelled the incidence of hepatitis C among active PWID, and the prevalence of chronic infection among active PWID, ex-PWID, and immigrants in Norway to 2022. Methods We built a stochastic compartmental model, which was informed using data from national data sources, literature, and expert opinion. We report median values with 95% credible intervals (CrI). Results The model estimated 30 (95% Crl, 13–52) new infections among active PWID in 2022, or 0.37/100 (95% Crl, 0.17–0.65), down from a peak of 726 (95% Crl, 506–1067) in 2000. Across all groups, the model estimated 3202 (95% Crl, 1273–6601) chronically infected persons in 2022. Results were robust in sensitivity analyses. Conclusions Norway provides an example of the feasibility of hepatitis C elimination in a setting with a concentrated epidemic, high coverage of harm reduction services, and no treatment restrictions. Continued momentum is needed to further reduce the transmission and burden of hepatitis C in Norway. [ABSTRACT FROM AUTHOR]

The morbidity of children under five years due to diarrhea is very prevalent in Nairobi County. Mathematical models can be used to study the dynamics of infections and suggest possible control strategies in the process. In this study, a deterministic model has been developed to investigate the impact of hygiene and treatment as control strategies, on the dynamics of diarrhea in children under five years of age in Nairobi County. In the analysis of the model, it was shown that the disease‐free equilibrium of the model was locally and globally asymptotically stable if the effective reproduction number was less than unity, while the endemic equilibrium point was locally and globally asymptotically stable if the effective reproduction number was greater than unity. From the sensitivity analysis of the effective reproduction number, it was observed that the sensitivity indices of the effective contact rate, the fraction of children joining the infected classes and modification parameters, are positive, while the indices of the rate of being born five years ago, hygiene compliance, natural death rate, rate of gaining symptoms, death rates due to diarrhea, treatment rates for infected children, recovery rates for treated children, and discharge rate are negative. From scenario simulations of the model, it was observed that when hygiene compliance strategy is increased, the disease is decreased and when it is equal to one, that is, when it is fully embraced, the disease is completely eradicated. It was observed that by increasing the treatment rate for mildly infected and treatment rate for severely infected children, the disease is controlled. It was lastly found that by increasing both the treatment rate for mildly infected children and hygiene compliance, the disease dies out and by increasing both the treatment rate for severely infected children and hygiene compliance, the disease is also eradicated completely. From the results, it was noted that by increasing hygiene compliance, the disease is completely wiped out as compared to treatment. It was also noted that for the two strategies combined, the disease is wiped out after 20 days if increased, while for the hygiene compliance strategy alone, the disease is wiped out after 40 days if fully embraced. Thus, it was concluded that both hygiene compliance and treatment are the best control strategies if fully embraced for the complete eradication of the disease within a shorter period of time. [ABSTRACT FROM AUTHOR]

Background: In the eradication of Helicobacter pylori, the efficacy of bismuth remains inconclusive. We aimed to compare the efficacy of bismuth on various H. pylori eradication regimens. Methods: Randomized controlled trials were collected to compare the efficacy of bismuth to nonbismuth regimens in H. pylori eradication. We pooled information to study eradication, adverse events, and drug compliance. In addition, subgroup analyses for eradication efficacy were performed according to high or low clarithromycin‐resistance area, bismuth drug form, and amount of bismuth element. Results: Records for a total of 2506 patients in 15 trials from 13 randomized controlled studies were included. The eradication of H. pylori was superior when bismuth compared to nonbismuth regimen (odds ratio [OR] = 1.63, 95% confidence interval [CI], 1.33–2.00 in intention‐to‐treat [ITT]; OR = 2.05, 95% CI, 1.58–2.68 in per‐protocol [PP] analyses), without significant difference in drug compliance or adverse events. Bismuth regimens in the high clarithromycin resistance area tend to enhance the eradication rate (OR = 1.66, 95% CI, 1.34–2.05 in ITT; OR = 2.22, 95% CI, 1.67–2.95 in PP analyses). Bismuth potassium citrate and bismuth subcitrate were more effective drug forms in regard to eradication rate. Bismuth at a dosage of < 500 mg/day was significantly higher for the eradication rate. Conclusions: Bismuth to the H. pylori eradication regimens achieve a higher eradication rate, especially in the high clarithromycin resistance area. It could be an eradication option achieving sufficient resistance rates without increasing antibiotic resistance, side effects, or poor compliance. [ABSTRACT FROM AUTHOR]

Simple Summary: Cryoablation therapy is an emerging modality in the treatment of Barrett's esophagus. Our systematic review collected data on this technique to provide evidence of its efficacy and safety and to compare it with the established RFA. The results from twenty-three studies revealed that the complete eradication of dysplasia and intestinal metaplasia was comparable between RFA and cryoablation. More specifically, cryoablation achieved a complete eradication of dysplasia and intestinal metaplasia at rates of 84.2% (95%CI: 79.1–89.3) and 64.1% (95%CI: 49.2–79.0), respectively, whereas 8.3% (95%CI: 4.7–11.9) of cases presented with recurrence. Studies on cryoballoons seem to be more homogenous in terms of dysplasia treatment, complications, and, especially, strictures. Background: The mainstay approach in endoscopic eradication therapy (EET) for dysplastic Barrett's esophagus (BE) includes the endoscopic resection of visible lesions, accompanied by ablation of the residual metaplastic epithelium. Cryoablation therapy is one such emerging ablation technique in this field. This systematic review with a meta-analysis aims to accumulate pooled data on cryoablation performance in the treatment of patients with BE and to compare this technique to the standard of care radiofrequency ablation (RFA). Methods: The MEDLINE, Cochrane, and Scopus databases were searched until June 2024 for studies evaluating BE management using cryoablation for cumulative results. The primary outcome was the complete eradication of dysplasia (CED) and intestinal metaplasia (CEIM) in BE compared to RFA, while secondary outcomes included the respective pooled rates using cryoablation, recurrence, and adverse events, with a separate analysis for strictures. The meta-analyses were based on a random-effects model, and the results were reported as odds ratios (ORs) with 95% confidence intervals (CIs). Subgroup analyses by type of cryoablation were also performed. Results: Twenty-three studies (1604 patients) were finally included, four of which were comparative. CED and CEIM did not differ significantly between cryoablation and RFA [OR= 0.95 (95%CI: 0.50–1.81) and OR = 0.57 (95%CI: 0.20–1.63), respectively)]. The pooled rates of CED, CEIM, and recurrence after cryoablation were 84.2% (95%CI: 79.1–89.3), 64.1% (95%CI: 49.2–79.0), and 8.3% (95%CI: 4.7–11.9), accompanied by high rates of heterogeneity. Adverse events were noted in 14.5% (95%CI: 9.9–19.2) of cases, and 6.5% (95%CI: 4.1–9.0) developed strictures. In the subgroup analysis, the cryoballoon achieved a reduction in heterogeneity in CED, adverse events, and stricture formation, whereas spray catheters provided homogenous results in terms of recurrence. Conclusions: Cryoablation provides equal outcomes compared to RFA in the treatment of patients with BE, with the cryoballoon achieving relatively homogenous rates of CED and adverse events. [ABSTRACT FROM AUTHOR]

Introduction: The ongoing visceral leishmaniasis (VL) elimination programme in India is targeting the elimination of the disease VL but not the pathogen. The persistence of hidden parasite pool may initiate a resurgence in suitable conditions. This study dealt with a novel approach to unearth such pathogen pool and their proper management to prevent the resurgence of VL. Materials and Methods: We deployed a new approach for detection of pathogen pool by following up the VL and post kala-azar dermal leishmaniasis patients treated during the last 10 years along with mass sero-surveillance within a radius of 500 m of recently treated individuals. Results: We followed up 72.6% (3026/4168) previously treated VL and post kala-azar dermal leishmaniasis patients and diagnosed 42 (1.4%) new and 38 (1.3%) recurrent post kala-azar dermal leishmaniasis. We detected 93 asymptomatic leishmanial infection, 8 VL and 1 post kala-azar dermal leishmaniasis by mass sero-surveillance. Conclusion: Our three-step process including mapping and follow-up of previously treated cases, mass surveillance within 500 m of radius of known cases, and 6 monthly follow-on clinical and serological screening of asymptomatic cases, enabled detection of previously undetected cases of post kala-azar dermal leishmaniasis and VL. Recurrent post kala-azar dermal leishmaniasis deserves special attention regarding their treatment guideline. Early diagnosis and effective treatment of all leishmaniasis cases will hasten pathogen elimination and prevent resurgence of VL. This may help the policymakers to develop appropriate strategy for elimination of pathogen to prevent resurgence of VL. [ABSTRACT FROM AUTHOR]

A reflection on public policies to combat Tuberculosis. A global panorama Tuberculosis is an infectious bacterial disease caused by Mycobacterium tuberculosis, mainly affecting the lungs and transmitted from person to person through respiratory droplets. Although the infection does not always cause symptoms in healthy people, when active, it can cause coughing, chest pain, weakness, weight loss and fever. Tuberculosis is currently a global health concern, with millions of deaths and new infections each year, due to factors such as drug resistance, HIV, international travel and homelessness. With a third of the world's population infected, it is essential that healthcare professionals understand the disease and its diagnostic procedures. New research should focus on the social factors that determine TB. In this way, it is believed, Brazil will once again be able to celebrate reaching the WHO targets for the elimination of TB by 2035. [ABSTRACT FROM AUTHOR]

Foot-and-mouth disease (FMD) is globally recognized as a highly economically devastating and prioritized viral disease affecting livestock. Vaccination remains a crucial preventive measure against FMD. The improvement of current vaccine platforms could help control outbreaks, leading to the potential eradication of the disease. In this review, we describe the variances in virulence and immune responses among FMD-susceptible host species, specifically bovines and pigs, highlighting the details of host–pathogen interactions and their impact on the severity of the disease. This knowledge serves as an important foundation for translating our insights into the rational design of vaccines and countermeasure strategies, including the use of interferon as a biotherapeutic agent. Ultimately, in this review, we aim to bridge the gap between our understanding of FMDV biology and the practical approaches to control and potentially eradicate FMD. [ABSTRACT FROM AUTHOR]

In this paper, we develop discrete models of Tuberculosis (TB). This includes SEI endogenous and exogenous models without treatment. These models are then extended to a SEIT model with treatment. We develop two types of net reproduction numbers, one is the traditional R0 which is based on the disease-free equilibrium, and a new net reproduction number R0 (E*) based on the endemic equilibrium. It is shown that the disease-free equilibrium is globally asymptotically stable if R0 ≤ 1 and unstable if R0 > 1. Moreover, the endemic equilibrium is locally asymptotically stable if R0(E*) < 1 < R0. [ABSTRACT FROM AUTHOR]

Symptomatic and asymptomatic individuals play a significant role in the transmission dynamics of novel Coronaviruses. By considering the dynamical behaviour of symptomatic and asymptomatic individuals, this study examines the temporal dynamics and optimal control of Coronavirus disease propagation using an epidemiological model. Biologically and mathematically, the well-posed epidemic problem is examined, as well as the threshold quantity with parameter sensitivity. Model parameters are quantified and their relative impact on the disease is evaluated. Additionally, the steady states are investigated to determine the model's stability and bifurcation. Using the dynamics and parameters sensitivity, we then introduce optimal control strategies for the elimination of the disease. Using real disease data, numerical simulations and model validation are performed to support theoretical findings and show the effects of control strategies. [ABSTRACT FROM AUTHOR]

This article proposes a dispersal strategy for infected individuals in a spatial susceptible-infected-susceptible (SIS) epidemic model. The presence of spatial heterogeneity and the movement of individuals play crucial roles in determining the persistence and eradication of infectious diseases. To capture these dynamics, we introduce a moving strategy called risk-induced dispersal (RID) for infected individuals in a continuous-time patch model of the SIS epidemic. First, we establish a continuous-time n-patch model and verify that the RID strategy is an effective approach for attaining a disease-free state. This is substantiated through simulations conducted on 7-patch models and analytical results derived from 2-patch models. Second, we extend our analysis by adapting the patch model into a diffusive epidemic model. This extension allows us to explore further the impact of the RID movement strategy on disease transmission and control. We validate our results through simulations, which provide the effects of the RID dispersal strategy. [ABSTRACT FROM AUTHOR]

Objective To investigate the efficacy, safety, compliance, and economic benefits of low-dose or standard-dose vonoprazan quadruple therapy for the eradication of Helicobacter pylori (Hp). Methods A total of 531 patients who were diagnosed with Hp infection in our hospital from March to August 2023 were enrolled and divided into esomeprazole (Ebid) group (oral administration of esomeprazole 20 mg twice a day), standard vonoprazan (Vbid) group (oral administration of vonoprazan 20 mg twice a day), and low-dose vonoprazan (Vqd) group (oral administration of vonoprazan 20 mg once a day), and the remaining three drugs of Hp quadruple therapy were the same for the three groups (oral administration of amoxicillin 1 000 mg, cla-rithromycin 500 mg, and bismuth potassium citrate 600 mg, twice a day), with a course of treatment of 14 days. All patients were examined for Hp eradication rate (based on the intention-to-treat [ITT] analysis and the per-protocol [PP] analysis), symptom improvement, adverse events, and patient compliance after 4 weeks of drug withdrawal, and a cost-effectiveness analysis was pe-rformed for the regimens in each group (including the ITT and PP analyses). Results There was a significant difference in Hp eradication rate between the three groups in the ITT and PP analyses (χ2ITT=6.351,PITT0.05). All three groups had mild adverse events, and the Vqd group had a significantly lower incidence rate of adverse events than the Ebid group (χ2=6.058,P0.05), with a compliance rate of >95% in all three groups. The Vqd group had a lower cost-effectiveness ratio than the Vbid and Ebid groups in both ITT and PP analyses. Conclusion The low-dose vonoprazan quadruple regimen has comparable efficacy to the standard-dose regimen, and both regimens have better efficacy than esomeprazole quadruple regimen. The low-dose vonoprazan quadruple regimen has better safety and cost-effectiveness and thus holds promise for clinical application in Hp eradication therapy.

Introduction: There is limited guidance on strategies for delivering complex global health programs. We synthesized available evidence on implementation strategies and outcomes utilized in the global polio eradication initiative (GPEI) across low and middle-income country (LMIC) settings. Methods: We nested our scoping review into a literature review conducted as part of a parent study, STRIPE. This review systematically searched PubMed for articles between 1 January 1988 and 25 April 2018 using polio search terms. Strategies from included studies were organized according to the Expert Recommendations for Implementing Change (ERIC) framework, specified using Proctor's framework, and linked to various outcomes (implementation, services delivery, impact). Results: 152 unique articles fulfilled our inclusion criteria (from 1,885 articles included in the parent study). Only 43 out of the 152 articles described a suitable quantitative study design for evaluating outcomes. We extracted 66 outcomes from the 43 unique studies. Study publication dates ranged from 1989 to 2018 and represented diverse country settings. The most common implementation strategies were developing mechanisms for feedback, monitoring, and evaluation (n = 69); increasing awareness among the population (n = 58); involving stakeholders, workers, and consumers in the implementation efforts (n = 46); conducting workshops (n = 33); using mass media (n = 31); and building robust record systems to capture outcomes (n = 31). Coverage (n = 13) and morbidity (n = 12) were the most frequently identified outcomes, followed by effectiveness (n = 9) and fidelity (n = 6). Feasibility and sustainability were rarely evaluated. Conclusions: This review provides a catalogue of implementation strategies and outcomes relevant for advancing global health services delivery in LMICs drawing from the GPEI. Implementation strategies reviewed were poorly described and not adequately linked to outcomes. It calls for additional implementation research to unravel the mechanisms of implementation strategies and their effectiveness, and adaptation of the ERIC framework in LMICs. [ABSTRACT FROM AUTHOR]

Background: The 2021 World Health Organization (WHO) guidelines on cervical cancer screening and treatment provide countries with evidence-based recommendations to accelerate disease elimination. However, evidence shows that health providers' adherence to screening guidelines is low. We conducted a study in Argentina to analyze health providers' knowledge and perceptions regarding the 2021 WHO Guidelines. Methods: A qualitative study was conducted based on individual, semi-structured interviews with health providers specializing in gynecology (n = 15). The themes explored were selected and analyzed using domains and constructs of the Consolidated Framework for Implementation Research. Results: Although health providers perceive WHO as a reliable institution, they do not know the 2021 guidelines, its supporting evidence, and its elaboration process. Their clinical practice is mainly guided by local recommendations developed by national professional medical associations (PMAs). For interviewees, WHO guidelines should be disseminated through health authorities and national PMAs, mainly through in-service training. Health providers had a positive assessment regarding WHO Recommendation 1 (screen, triage, and treatment for women aged 30 + with HPV-testing every 5 to 10 years) and perceived a favorable climate for its implementation. HPV-testing followed by triage was considered a low-complexity practice, enabling a better detection of HPV, a better selection of the patients who will need diagnosis and treatment, and a more efficient use of health system resources. However, they suggested adapting this recommendation by removing screening interval beyond 5 years. WHO Recommendation 2 (screen-and-treat approach with HPV-testing for women aged 30 + every 5 to 10 years) was predominantly rejected by interviewees, was considered an algorithm that did not respond to women's needs, and was not adequate for the Argentinean context. Regarding the HPV-test modality, clinician-collected tests were the preferred mode. Health providers considered that HPV self-collection should be used primarily among socially vulnerable women to increase screening coverage. Conclusion: WHO guidelines should be widely disseminated among health providers, especially in settings that could benefit from a screen-and-treat approach. Identifying areas of partnership and collaboration with PMAs in implementing WHO guidelines is essential. [ABSTRACT FROM AUTHOR]

In this paper, we develop and analyze a mathematical model for spreading malaria, including treatment with transmission‐blocking drugs (TBDs). The paper's main aim is to demonstrate the impact the chosen model for demographic growth has on the disease's transmission and the effect of its treatment with TBDs. We calculate the model's control reproduction number and equilibria and perform a global stability analysis of the disease‐free equilibrium point. The mathematical analysis reveals that, depending on the model's demography, the model can exhibit forward, backward, and even some unconventional types of bifurcation, where disease elimination can occur for both small and large values of the reproduction number. We also conduct a numerical analysis to explore the short‐time behavior of the model. A key finding is that for one type of demographic growth, the population experienced a significantly higher disease burden than the others, and when exposed to high levels of treatment with TBDs, only this population succeeded in effectively eliminating the disease within a reasonable timeframe. [ABSTRACT FROM AUTHOR]

This paper presents an in‐depth analysis of a hybrid mathematical model, the fractional SECIR model, designed to explore the impact of infectious diseases, with particular emphasis on their effect on individuals with chronic conditions. The study delves into the existence and uniqueness of solutions for the proposed model, yielding several stability results based on parameters that adhere to specific conditions to mitigate pandemic occurrences. The model parameters are estimated using data reported by the Algerian health authorities in recent years, facilitating the application of the model to the Algerian context. The findings derived from the application of this mathematical compartmental model indicate that the basic reproduction number for certain infectious diseases in Algeria (Tuberculosis and COVID‐19) is less than one. This observation suggests the potential for disease eradication or effective management through a combination of targeted interventions including vaccination, high‐quality treatment, and precise isolation measures. [ABSTRACT FROM AUTHOR]

PURPOSE: H. pylori eradication therapy (HPE) can lead to tumor regression in H. pylori –positive (HPP) gastric mucosa-associated lymphoid tissue (MALT) lymphoma. However, some patients do not have detectable H. pylori (HP) infection (H. pylori –negative [HPN]) and the guidelines differ in their initial approach to HPN patients. The National Comprehensive Cancer Network (NCCN) recommends proceeding to radiation therapy, whereas European Society for Medical Oncology suggests HPE for every patient, even those who are HPN. To address this issue, we evaluated the effectiveness of HPE in limited-stage gastric MALT lymphoma. MATERIALS AND METHODS: We retrospectively reviewed patients newly diagnosed with stage IE gastric MALT lymphoma between January 2002 and December 2022. The primary outcome was the complete remission (CR) rate defined as no macroscopic findings of lymphoma and negative gastric biopsy at the follow-up gastric endoscopy. RESULTS: Fifty-two patients were reviewed, and HP infection was detected in 19 (36.5%) patients—14 by immunostaining, three by serology, and one each by stool antigen and urea breath test. All 19 HPP and eight of the 33 HPN patients received HPE treatment. The CR rate was 63% (12/19) in HPP patients and 13% (1/8) in HPN patients (P =.033). After a median follow-up of 89.7 months, only two of the 12 HPP patients achieving CR have relapsed; the one HPN patient who received HPE remains in CR at 12+ months. CONCLUSION: For limited-stage HPP gastric MALT lymphoma, HPE is an effective and durable first-line treatment and should be used. For HPN patients, the CR rate with HPE is very low in our experience and is thus in support of the NCCN guideline. Patients with H. pylori-negative stage 1 gastric MALT can proceed to radiotherapy without a trial of antibiotics. [ABSTRACT FROM AUTHOR]

Efforts to control and eliminate measles and rubella are aided by high-quality surveillance data—supported by laboratory confirmation—to guide decision-making on routine immunization strategies and locations for conducting preventive supplementary immunization activities (SIAs) and outbreak response. Important developments in rapid diagnostic tests (RDTs) for measles and rubella present new opportunities for the global measles and rubella surveillance program to greatly improve the ability to rapidly detect and respond to outbreaks. Here, we review the status of RDTs for measles and rubella Immunoglobulin M (IgM) testing, as well as ongoing questions and challenges regarding the operational use and deployment of RDTs as part of global measles and rubella surveillance. Efforts to develop IgM RDTs that can be produced at scale are underway. Once validated RDTs are available, clear information on the benefits, challenges, and costs of their implementation will be critical for shaping deployment guidance and informing country plans for sustainably deploying such tests. The wide availability of RDTs could provide new programmatic options for measles and rubella elimination efforts, potentially enabling improvements and flexibility for testing, surveillance, and vaccination. [ABSTRACT FROM AUTHOR]

Helicobacter pylori infection has significant epidemiological relevance due to the carcinogenic nature of this bacterium, which is potentially associated with cancer. When detected, it should ideally be eradicated using a treatment that currently involves a combination of gastric acid suppressors and multiple antibiotics. However, this treatment raises questions regarding efficacy and safety profiles in patients with specific comorbidities, including inflammatory bowel diseases (IBD). Eradication therapy for H. pylori includes components associated with adverse gastrointestinal events, such as Clostridioides difficile colitis. This necessitates quantifying this risk through dedicated studies to determine whether this antimicrobial treatment could be significantly associated with IBD relapse or exacerbation of pre-existing IBD, as well as whether it could potentially lead to the de novo onset of IBD. Although the available evidence is reassuring about the safety of eradication therapy in patients with IBD, it is limited, and there are no specific recommendations for this particular situation in the leading international IBD and H. pylori guidelines. Therefore, studies need to evaluate the efficacy and safety profiles of the available antimicrobial regimens for H. pylori eradication in patients with IBD, both in clinical trial settings and in real-life studies. [ABSTRACT FROM AUTHOR]

Egypt has long been overwhelmed by the hepatitis C virus (HCV) infection, and it used to be the country with the world's highest prevalence rates. The disease had been a significant public health problem, affecting millions of Egyptians and posing severe economic and social challenges. By the early 2000s, it was estimated that around 10% of the Egyptian population was infected with HCV. However, in recent years, with the availability of direct-acting antiviral therapies, the country has made enormous steps in combating this public health threat. The combination of innovative health strategies and political will enabled Egypt to establish a successful model of care for HCV management and to be the first country to eliminate hepatitis C, setting a model for the rest of the world. In 2023, Egypt became the first country to fulfill the World Health Organization's set programmatic criteria of reduction of hepatitis C incidence and mortalities to levels close to elimination of disease or achieve the "gold tier" status on the path to disease elimination. [ABSTRACT FROM AUTHOR]

Demodex blepharitis, a chronic lid margin disease, is caused by an infestation of Demodex mites, the most common ectoparasites in human skin and eyelids. Lotilaner ophthalmic solution, 0.25% (Xdemvy, Tarsus Pharmaceuticals), is the first therapy approved to treat Demodex blepharitis. This narrative review characterizes lotilaner ophthalmic solution, 0.25%, and describes its efficacy, safety, and tolerability. The safety and efficacy of lotilaner ophthalmic solution, 0.25%, for treating Demodex blepharitis was evaluated in four phase 2 and two phase 3 trials. The data of 980 patients included in these phase 2 and 3 clinical trials revealed that the proportion of eyes with a clinically meaningful reduction to 10 or fewer collarettes (the cylindrical, waxy debris found at the base of the eyelashes) ranged from 81 to 93%. The mite eradication rate confirmed by a microscopy of epilated lashes ranged from 52 to 78%. No serious treatment-related adverse events were reported in any of these clinical studies. As high as 92% of the patients receiving lotilaner eyedrops in the phase 3 trials found it to be neutral to very comfortable. Given the positive safety and efficacy outcomes, the drug is likely to become the standard of care in the treatment of Demodex blepharitis. [ABSTRACT FROM AUTHOR]

Tumor related angiogenesis is an attractive target in cancer therapeutic research due to its crucial role in tumor growth, invasion, and metastasis. Different agents were developed aiming to inhibit this process; however they had limited success. Cancer vaccines could be a promising tool in anti-cancer/anti-angiogenic therapy. Cancer vaccines aim to initiate an immune response against cancer cells upon presentation of tumor antigens which hopefully will result in the eradication of disease and prevention of its recurrence by inducing an efficient and long-lasting immune response. Different vaccine constructs have been developed to achieve this and they could include either protein-based or nucleic acid-based vaccines. Nucleic acid vaccines are simple and relatively easy to produce, with high efficiency and safety, thus prompting a high interest in the field. Different DNA vaccines have been developed to target crucial regulators of tumor angiogenesis. Most of them were successful in pre-clinical studies, mostly when used in combination with other therapeutics, but had limited success in the clinic. Apparently, different tumor evasion mechanisms and reduced immunogenicity still limit the potential of these vaccines and there is plenty of room for improvement. Nowadays, mRNA cancer vaccines are making remarkable progress due to improvements in the manufacturing technology and represent a powerful potential alternative. Apart from their efficiency, mRNA vaccines are simple and cheap to produce, can encompass multiple targets simultaneously, and can be quickly transferred from bench to bedside. mRNA vaccines have already accomplished amazing results in cancer clinical trials, thus ensuring a bright future in the field, although no anti-angiogenic mRNA vaccines have been described yet. This review aims to describe recent advances in anti-angiogenic DNA vaccine therapy and to provide perspectives for use of revolutionary approaches such are mRNA vaccines for anti-angiogenic treatments. [ABSTRACT FROM AUTHOR]

Cholera remains a significant public health concern in Ethiopia. More than 15.9 million Ethiopians, constituting 15% of the total population, live in areas with a history of recurrent cholera outbreaks. The last 9 years of national cholera surveillance data show the country has been experiencing cholera outbreaks every year. The current cholera outbreak, starting in August 2022, has affected the entire country, with 841 reported cases and a 3.13% case fatality rate (CFR) in 2022, and >30 000 cases with nearly a 1.4% CFR in 2023. In line with "Ending Cholera—A Global Roadmap to 2030," the government of Ethiopia is committed to eliminate cholera in the country and has prepared its "National Cholera Elimination Plan (NCP): 2022–2028" with aims to achieve zero local transmission in cholera hotspot areas by 2028 and 90% fatality reduction from the recent (2020–2022) average of 1.8% CFR. The plan is multisectoral, has a clear coordination platform, contains all interventions with in-depth situational analysis, is concordant with existing plans and strategies, and is cascaded at the regional level and implemented with existing government and public structures. Nationwide, total 118 cholera hotspot woredas (districts) were identified, and a comprehensive situation analysis of the existing cholera outbreak response capacity was assessed. This multisectoral and multiyear NCP has forecasted around US$404 million budget estimates with >90% allocated to improving the country's water, sanitation, and hygiene (US$222 million; 55% of total NCP budget) and case management (US$149 million; 37%). The cholera vaccination strategy included in the NCP exhibited a 5-year oral cholera vaccine (OCV) introduction plan with 2 doses (30 604 889 doses) and single dose (3 031 266 doses) in selected cholera hotspot areas. However, its implementation is challenged due to a lack of financial support, inability to get the requested vaccine for targeted hotspot woredas (due to the current shortage of doses in the OCV global stockpile), recurrent cholera outbreaks, and high humanitarian needs in the country. It is recommended to have a sustainable financial mechanism to support implementation, follow the requested vaccine doses, and reorganize the planned coordination platform to foster the implementation. [ABSTRACT FROM AUTHOR]

Background: Despite curative treatment options since 2014, only 12% of individuals in Washington State diagnosed with Hepatitis C (HCV) received treatment in 2018. Washington State agencies launched an elimination plan in 2019 to promote access to and delivery of HCV screening and treatment. The purpose of this study is to evaluate provider and health system barriers to successful implementation of HCV screening and treatment across Washington State. Methods: This is a cross-sectional online survey of 547 physicians, nurse practitioners, physician assistants, and clinical pharmacists who provide care to adult patients in Washington State conducted in 2022. Providers were eligible if they worked in a primary care, infectious disease, gastroenterology, or community health settings. Questions assessed HCV screening and treating practices, implementation barriers, provider knowledge, observed stigma, and willingness to co-manage HCV and substance use disorder. Chi-squared or fishers exact tests compared characteristics of those who did and did not screen or treat. Results: Provider adoption of screening for HCV was high across the state (96%), with minimal barriers identified. Fewer providers reported treating HCV themselves (28%); most (71%) referred their patients to another provider. Barriers identified by those not treating HCV included knowledge deficit (64%) and lack of organizational support (24%). The barrier most identified in those treating HCV was a lack of treating clinicians (18%). There were few (< 10%) reports of observed stigma in settings of HCV treatment. Most clinicians (95%) were willing to prescribe medication for substance use disorders to those that were using drugs including alcohol. Conclusion: Despite widespread screening efforts, there remain barriers to implementing HCV treatment in Washington State. Lack of treating clinicians and clinician knowledge deficit were the most frequently identified barriers to treating HCV. To achieve elimination of HCV by 2030, there is a need to grow and educate the clinician workforce treating HCV. [ABSTRACT FROM AUTHOR]

An improved understanding of the Plasmodium vivax populations in the Great Mekong Subregion (GMS) is needed to monitor the progress of malaria elimination. This study aimed to use a P. vivax single nucleotide polymorphism (SNP) barcode to evaluate the population dynamics and explore the gene flow among P. vivax parasite populations in the western GMS (China, Myanmar and Thailand). A total of 315 P. vivax patient samples collected in 2011 and 2018 from four regions of the western GMS were genotyped for 42 SNPs using the high-throughput MassARRAY SNP genotyping technology. Population genetic analysis was conducted to estimate the genetic diversity, effective population size, and population structure among the P. vivax populations. Overall, 291 samples were successfully genotyped at 39 SNPs. A significant difference was observed in the proportion of polyclonal infections among the five P. vivax populations (P = 0.0012, Pearson Chi-square test, χ2 = 18.1), with western Myanmar having the highest proportion (96.2%, 50/52) in 2018. Likewise, the average complexity of infection was also highest in western Myanmar (1.31) and lowest in northeast Myanmar (1.01) in 2018. The older samples from western China in 2011 had the highest pairwise nucleotide diversity (π, 0.388 ± 0.046), expected heterozygosity (He, 0.363 ± 0.02), and the largest effective population size. In comparison, in the neighboring northeast Myanmar, the more recent samples in 2018 showed the lowest values (π, 0.224 ± 0.036; He, 0.220 ± 0.026). Furthermore, the 2018 northeast Myanmar parasites showed high and moderate genetic differentiation from other populations with FST values of 0.162–0.252, whereas genetic differentiation among other populations was relatively low (FST ≤ 0.059). Principal component analysis, phylogeny, and STRUCTURE analysis showed that the P. vivax population in northeast Myanmar in 2018 substantially diverged from other populations. Although the 42 SNP barcode is a valuable tool for tracking parasite origins of worldwide parasite populations, a more extended barcode with additional SNPs is needed to distinguish the more related parasite populations in the western GMS. Author summary: In the Great Mekong Subregion (GMS), particularly in Myanmar, vivax malaria remains a significant challenge to malaria elimination. To effectively evaluate the impact of ongoing malaria control measures, it is essential to understand the genetic diversity, relatedness, and population dynamics of the malaria parasite. A comprehensive analysis of P. vivax populations in the western GMS using a global 42-SNP barcode revealed notable changes over time. Compared to the more homogeneous parasite populations a decade ago, there has been a decrease in genetic diversity and an increase in differentiation among parasite populations in recent years, particularly along the China-Myanmar border. In comparison, the 2018 parasites from western Myanmar showed a relatively stable genetic structure, underscoring the persistent challenge of vivax malaria in this region. While the 42-SNP barcode has been valuable in understanding the genetic landscape of global P. vivax populations, it has limitations in accurately differentiating parasite populations across the GMS, necessitating a barcode tailored to the local parasite populations. [ABSTRACT FROM AUTHOR]

Indirect disease transmission is modeled via a fractional-order discretetime Susceptible-Infected-Contaminant (SIC) model vaccination as a control strategy. Two control actions are considered, giving rise to two different models: the vaccine efficacy model and the vaccination impact model. In the first model, the effectiveness of the vaccine is analyzed by introducing a new parameter, while in the second model, the impact of the vaccine is studied incorporating a new variable into the model. Both models are studied giving population thresholds to ensure the eradication of the disease. In addition, a sensitivity analysis of the Basic Reproduction Number has been carried out with respect to the effectiveness of the vaccine, the fractional order, the vaccinated population rate and the exposure rate. This analysis has been undertaken to study its effect on the dynamics of the models. Finally, the obtained results are illustrated and discussed with a simulation example related to the evolution of the disease in a pig farm. [ABSTRACT FROM AUTHOR]

Radiation therapy may induce off-target antitumor "abscopal" immunostimulatory and immunosuppressive effects. Several preclinical and early clinical studies revealed promising results when combining radiation therapy with immunostimulatory agents. Most radioimmunotherapy randomized trials showed disappointing results in patients with advanced tumors. In contrast, outcomes were encouraging when immunotherapy was delivered on top of gross disease elimination with curative-intent radiation therapy. In this review, we highlight available results from randomized trials and discuss the potential impact of overall tumor burden on the observed efficacy of radioimmunotherapy. [ABSTRACT FROM AUTHOR]

Sheep pox and goat pox are infectious viral diseases that affect ovine and caprine animals and are caused by two viruses of the family Poxviridae, genus Capripoxvirus. Sheep pox has been traditionally endemic in Africa, the Middle East, and several Southeast Asian countries, but it is considered a transboundary disease capable of affecting previously free countries epidemically. It is a disease of compulsory immediate notification to the World Organization for Animal Health (WOAH) and the European Union (EU). On 19 September 2022, the disease reemerged in Spain, which had been free of it since 1968, causing a total of 30 outbreaks until 17 May 2023, when the last outbreak of the disease was reported. The control and eradication measures implemented were those laid down in EU legislation, based on the total stamping out of positive herds, zoning and restriction of movement, and strengthening of biosecurity and passive surveillance. This manuscript describes the outbreak, as well as assesses the challenges and lessons learned in relation to its management, with the aim of helping in the effective management of future outbreaks of this disease. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with pediatric liver cancers hepatoblastoma and hepatocellular carcinoma very often develop lung metastases. These cancers can present with lung metastases and are at higher risk of relapse. Although cisplatin is very effective at clearing lung metastases, they can still relapse. Therefore, there is an urgent need to develop therapeutic approaches to prevent the development of lung metastases in patients with pediatric liver cancers. In this paper, we show that the metastatic microenvironment of HBL and HCC patients contains a heterogeneous cell population that formed tumor clusters. We found that both fresh primary tumors and generated primary cell cultures had increased the expression of HDAC1, a histone deacetylase, and the transcription factor Sp5. Sp5 and HDAC1 work in tandem by transporting HDAC1 to the promoters of genes and changing their expression. We analyzed the effects of the HDAC inhibitor, SAHA, on the metastasis-initiating cells in combination with cisplatin. We found that HDAC inhibition increases the efficacy of cisplatin to eliminate these metastasis-initiating cells. The pediatric liver cancers, hepatoblastoma and hepatocellular carcinoma, are dangerous cancers which often spread to the lungs. Although treatments with cisplatin significantly improve outcomes, cisplatin may not eliminate metastasis-initiating cells. Our group has recently shown that the metastatic microenvironments of hepatoblastoma contain Cancer Associated Fibroblasts (CAFs) and neuron-like cells, which initiate cancer spread from liver to lungs. In this study, we found that these cells express high levels of HDAC1; therefore, we examined if histone deacetylase inhibition improves cisplatin anti-proliferative effects and reduces the formation of tumor clusters in pediatric liver cancer metastatic microenvironments. Methods: New cell lines were generated from primary hepatoblastoma liver tumors (hbl) and lung metastases (LM) of HBL patients. In addition, cell lines were generated from hepatocellular neoplasm, not otherwise specified (HCN-NOS) tumor samples, and hcc cell lines. Hbl, LM and hcc cells were treated with cisplatin, SAHA or in combination. The effect of these drugs on the number of cells, formation of tumor clusters and HDAC1-Sp5-p21 axis were examined. Results: Both HBL and HCC tissue specimens have increased HDAC1-Sp5 pathway activation, recapitulated in cell lines generated from the tumors. HDAC inhibition with vorinostat (SAHA) increases cisplatin efficacy to eliminate CAFs in hbl and in hcc cell lines. Although the neuron-like cells survive the combined treatments, proliferation was inhibited. Notably, combining SAHA with cisplatin overcame cisplatin resistance in an LM cell line from an aggressive case with multiple metastases. Underlying mechanisms of this enhanced inhibition include suppression of the HDAC1-Sp5 pathway and elevation of an inhibitor of proliferation p21. Similar findings were found with gemcitabine treatments suggesting that elimination of proliferative CAFs cells is a key event in the inhibition of mitotic microenvironment. Conclusions: Our studies demonstrate the synergistic benefits of HDAC inhibition and cisplatin to eliminate metastasis-initiating cells in pediatric liver cancers. [ABSTRACT FROM AUTHOR]

Optimum genetic delivery for modulating target genes to diseased tissue is a major obstacle for profitable gene therapy. Lipid nanoparticles (LNPs), considered a prospective vehicle for nucleic acid delivery, have demonstrated efficacy in human use during the COVID-19 pandemic. This study introduces a novel biomaterial-based platform, M1-polarized macrophage-derived cellular nanovesicle-coated LNPs (M1-C-LNPs), specifically engineered for a combined gene-immunotherapy approach against solid tumor. The dual-function system of M1-C-LNPs encapsulates Bcl2 -targeting siRNA within LNPs and immune-modulating cytokines within M1 macrophage-derived cellular nanovesicles (M1-NVs), effectively facilitating apoptosis in cancer cells without impacting T and NK cells, which activate the intratumoral immune response to promote granule-mediating killing for solid tumor eradication. Enhanced retention within tumor was observed upon intratumoral administration of M1-C-LNPs, owing to the presence of adhesion molecules on M1-NVs, thereby contributing to superior tumor growth inhibition. These findings represent a promising strategy for the development of targeted and effective nanoparticle-based cancer genetic-immunotherapy, with significant implications for advancing biomaterial use in cancer therapeutics. M1-polarized macrophage-derived cellular nanovesicle-coated lipid nanoparticles (M1-C-LNPs) were designed for combined gene and immunotherapy against solid tumors, with superior tumor inhibition efficacy and safety from targeted delivery and immune activation. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: In Japan, the standard management of Barrett's esophageal adenocarcinoma after endoscopic submucosal dissection involves follow-up; however, multifocal synchronous/metachronous lesions are sometimes observed after endoscopic submucosal dissection. Risk stratification of multifocal cancer facilitates appropriate treatment, including eradication of Barrett's esophagus in high-risk cases; however, no effective risk stratification methods have been established. Thus, we identified the risk factors for multifocal cancer and explored risk-stratified treatment strategies for residual Barrett's esophagus. Methods: We retrospectively reviewed the data of 97 consecutive patients with superficial Barrett's esophageal adenocarcinomas who underwent curative resection with endoscopic submucosal dissection. Multifocal cancer was defined by the presence of synchronous/metachronous lesions during follow-up. We used Cox regression analysis to identify the risk factors for multifocal cancer and subsequently analyzed differences in cumulative incidences. Results: The cumulative incidences of multifocal cancer at 1, 3, and 5 years were 4.4%, 8.6%, and 10.7%, respectively. Significant risk factors for multifocal cancer were increased circumferential and maximal lengths of Barrett's esophagus. The cumulative incidences of multifocal cancer at 3 years were lower for patients with circumferential length < 4 cm and maximal length < 5 cm (2.9% and 1.2%, respectively) than for patients with circumferential length ≥ 4 cm and maximal length ≥ 5 cm (51.5% and 49.1%, respectively). Conclusions: Risk stratification of multifocal cancer using length of Barrett's esophagus was effective. Further multicenter prospective studies are needed to substantiate our findings. [ABSTRACT FROM AUTHOR]

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Vaccination Week in the Americas (VWA) is a yearly regional initiative that promotes the benefits of vaccination to all persons in the region. In its 22-year history, more than 1.15 billion people have been reached under the framework of VWA across more than 40 countries and territories. This review examines multiple PAHO and WHO data points, documents and reports related to measles/rubella vaccination coverage and VWA since its inception. Its goal is to document the impact that the VWA has had in maintaining and accelerating measles and rubella disease elimination, in the context of PAHO's Disease Elimination Initiative. The results suggest that VWA's contributions to measles and rubella elimination have been substantial. Every year, VWA promotes (a) renewed political commitment to the immunization program from the highest political authorities of Member States; (b) vaccination operations to close immunity gaps, recover under-vaccinated persons, and reach chronically underserved populations; and (c) the dissemination of messages on the benefits of vaccination through regional and national communications campaigns. VWA will continue to be an important contributor to disease elimination efforts in the Americas, even as new targets are set in response to the evolving epidemiological landscape. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) infection is a global public health issue. We offer a comprehensive analysis of the dynamics of HBV, which can be successfully controlled with vaccine and treatment. Hepatitis B virus (HBV) causes a significantly more severe and protracted disease compared to hepatitis A. While it initially presents as an acute disease, in approximately 5 to 10% of cases, it can develop into a chronic disease that causes permanent damage to the liver. The hepatitis B virus can remain active outside the body for at least seven days. If the virus penetrates an individual's body without immunization, it may still result in infection. Upon exposure to HBV, the symptoms often last for a duration ranging from 10 days to 6 months. In this study, we developed a new model for Hepatitis B Virus (HBV) that includes asymptomatic carriers, vaccination, and treatment classes to gain a comprehensive knowledge of HBV dynamics. The basic reproduction number R0 is calculated to identify future recurrence. The local and global stabilities of the proposed model are evaluated for values of R0 that are both below and above 1. The Lyapunov function is employed to ensure the global stability of the HBV model. Further, the existence and uniqueness of the proposed model are demonstrated. To look at the solution of the proposed model graphically, we used a useful numerical strategy, such as the non-standard finite difference method, to obtain more thorough numerical findings for the parameters that have a significant impact on disease elimination. In addition, the study of treatment class in the population, we may assess the effectiveness of alternative medicines to treat infected populations can be determined. Numerical simulations and graphical representations are employed to illustrate the implications of our theoretical conclusions. [ABSTRACT FROM AUTHOR]

We construct a model to investigate HIV/AIDS dynamics in real cases and study its mathematical analysis. The study examines the qualitative outcomes and confirms the local and global asymptotic stability of both the endemic equilibrium and the disease-free equilibrium. The model's criteria for exhibiting both local and global asymptotically stable behavior are examined. We compute the endemic equilibria and obtain the existence of a unique positive endemic equilibrium. The data is fitted to the model using the idea of nonlinear least-squares fitting. Accurate parameter values are achieved by fitting the data to the model using a 95% confidence interval. The basic reproduction number is computed using parameters that have been fitted or estimated. Sensitivity analysis is performed to discover the influential parameters that impact the reproduction number and the eradication of the disease. The results show that implementing preventive measures can reduce HIV/AIDS cases. [ABSTRACT FROM AUTHOR]