There is paucity of data on recent trends of population-level deaths with Primary Immunodeficiency Diseases (PIDD). To examine the population-based temporal trends in deaths with PIDD in the United States from 2015 to 2022. We performed a retrospective, serial cross-sectional analysis of national death certificate data from 2015 through 2022. We evaluated the changes in the PIDD age-adjusted mortality rate per 1,000,000 (AAMR), overall, then stratified by age, gender, and race/ethnicity. The overall AAMR increased significantly from 2.5 to 3.5 (P<0.01). The AAMR rose significantly from 2.5 in the pre-COVID-19 era (2015-2019) to 3.2 in the COVID-19 era (2020-2022) [P = 0.03]. A similar trend was seen in several subgroups especially those aged ≥65 years. The overall PIDD AAMR increased during the study period, especially in those aged ≥65 years. This data can enhance PIDD awareness and reduce mortality, especially in older patients.

Examining smartphone usage behaviour in the COVID-19 era: Implications for post-pandemic usage and dependence patterns

Health inequalities and biopolitical state racism in the COVID-19 Era: A Foucauldian perspective on Seine-Saint-Denis, France

To evaluate the value of linked electronic health records (EHRs) for measuring stroke care quality in England before and after the COVID-19 pandemic, focusing on metrics not routinely captured: stroke incidence, dispensing of secondary prevention medications and a proxy of disability-time spent at home after stroke ('home-time'). Prospective cohort study using national linked datasets. England-wide health data linkage including the Sentinel Stroke National Audit Programme (SSNAP), primary and secondary care, dispensed medications and mortality records, accessed via National Health Service (NHS) England's Secure Data Environment. 425 675 adults with a first stroke between 1 January 2020 and 31 December 2023; data were available for 304 210 in primary care, 279 825 in hospital admissions, 220 470 in SSNAP and 59 465 in death records. Annual stroke incidence; first-year medication dispensing rates for antiplatelets, anticoagulants, antihypertensives and lipid-lowering agents (with a 1-month washout period) and home-time at 180 days post stroke. Stroke ascertainment was highest when combining all sources, with 10.8% of non-fatal ischaemic strokes recorded exclusively in primary care and 19.4% of fatal strokes identified solely through death records. Standardised annual stroke incidence rose from 227.6 (95% CI 226.1 to 229.0) to 244.8 (95% CI 243.4 to 246.3) per 100 000 over the study period including the COVID-19 pandemic. During the COVID-19 lockdown, non-fatal stroke recordings decreased while stroke-related deaths rose, indicating that recording quality was sensitive to shifts in healthcare-seeking behaviour during the pandemic. Among people with ischaemic stroke, 89.1% received an antiplatelet or anticoagulant, 44.5% an antihypertensive and 80.5% a lipid-lowering therapy. For haemorrhagic stroke, these proportions were: for anticoagulants 13.5%, antiplatelets 13.2%, antihypertensives 46.6% and lipid lowering 41.1%. Medication dispensing for stroke prevention declined with increasing age and comorbidity, but varied little by ethnicity, region or pandemic period. Mean home-time within 180 days of stroke was 166.6 (95% CI 166.4 to 166) days, decreasing with greater age (141.4 days for 90 years or older (95% CI 140.7 to 142.1)), deprivation (166.4 days (95% CI 166.1 to 166.6) for most deprived quintile) and stroke severity (137.4 days for National Institutes of Health Stroke Scale (NIHSS) score on arrival over 22 (95% CI 135.8 to 139.1)) and increasing with years from the COVID-19 pandemic 2023 (169.3 days (95% CI 169.0 to 169.5) vs 2020 164.4 days (95% CI 164.1 to 164.7)). Standardised stroke incidence increased significantly over the study period, highlighting a growing public health burden that persisted despite disruptions due to the pandemic although variation in case ascertainment and stroke coding practices was observed. While secondary prevention coverage for antiplatelets and lipids was high, lower rates of dispensing of antihypertensives, particularly in older and comorbid populations, potentially signal a target for improvement. Home-time represents a sensitive, person-centred outcome that exposes disparities linked to socioeconomic deprivation and clinical severity that can be used to enhance routine stroke audits. These findings justify the expansion of linked EHR infrastructure and the modernisation of governance frameworks to enable the longitudinal evaluation of care quality beyond the COVID-19 era.

Collaboration between local health authorities and community actors is widely recognised as central to effective emergency preparedness and response, particularly in low- and middle-income countries (LMICs), where health systems face persistent resource and governance constraints. However, empirical evidence on how such collaboration is conceptualised, operationalised, and evaluated remains fragmented. This scoping review mapped and synthesised available evidence on collaboration between local health authorities and community leaders (including community-facing actors) during health emergencies, using the COVID-19 pandemic as an illustrative context to inform further research. A scoping review was conducted following the Arksey and O'Malley framework and reported in accordance with the PRISMA-ScR guidelines. Searches were conducted in PubMed, Scopus, Web of Science, the Cochrane Library, and Google Scholar for studies published between January 2020 and October 2025. Eligible studies were primary empirical research conducted in LMICs that examined collaboration between local health authorities and community-facing actors involved in emergency responses. Data were extracted using a structured charting tool and synthesised using descriptive and narrative approaches. Three qualitative studies from Bangladesh and the Philippines met the inclusion criteria. Collaboration involved partnerships between local health authorities and non-governmental organisations, universities, and community-based actors, often formalised through coordination mechanisms. Reported strategies included joint planning, co-implementation of services, resource and workforce sharing, capacity building, and community outreach. These approaches were associated with enhanced surge capacity, continuity of essential services, strengthened system resilience, and improved access and community engagement. However, community leadership roles were rarely explicitly defined, with leadership functions often embedded within community-facing or intermediary actors. The evidence base on collaboration during health emergencies in LMICs remains limited and conceptually underdeveloped. Available studies suggest that collaboration between local health authorities and community-facing actors may support coordinated and resilient responses. However, important gaps persist in how community leadership is conceptualised, operationalised, and evaluated. Future research should more explicitly define and examine community leadership roles, alongside strengthening institutionalised and sustainable collaborative mechanisms for emergency preparedness and response. Not applicable. This scoping review does not involve a healthcare intervention or human participant enrolment. The review protocol has been published previously and is publicly accessible.

Objective:We evaluated how antibiotic use changed after implementation of a multifaceted intervention that sent providers individualized peer-comparison feedback on their antibiotic use for respiratory conditions that do not warrant antibiotics (never-events).Design:An interrupted time-series analysis was performed with a baseline (January 2018–January 2020) and intervention period (November 2021–December 2023), while controlling for COVID-19 era (February 2020–February 2022).Setting:Walk-in ambulatory clinics.Participants:Providers caring for patients in walk-in clinics.Methods:We conducted a mixed-methods study across 7 walk-in clinics in one health system. We included data from visits from 2018–2023 and conducted 17 semi-structured interviews with 10 providers.Results:After intervention implementation, antibiotic use for all visits decreased 8% (RR 0.92, 95% CI 0.86–0.97), then began to increase by 1% per month (RR 1.01, 95% CI 1.00–1.01). Once the intervention started, the use of never-event diagnostic codes decreased by 24% (RR 0.69–0.83) and continued to decrease by 1% per month (RR 0.99, 95% CI 0.98–0.99). Antibiotic use for never-event visits showed no immediate change after the intervention started (RR 0.80, 95% CI 0.61–1.04), then decreased by 3% per month (RR 0.97, 95% CI 0.96–0.98). Some providers valued receiving feedback on the metric; others admitted to shifting their codes.Conclusions:Delivering feedback to walk-in clinic providers was associated with temporary reductions in antibiotic-prescribing across all visits but also changes in diagnostic coding (ie, “gaming”). Antibiotic stewardship programs should monitor for changes in both when implementing new outpatient metrics.

ABSTRACT Geographies of bordering practices during the Covid-19 pandemic in societies with white majority cultures have focused on unjust harms experienced by displaced, disadvantaged and dispossessed people of colour. This article, however, makes a radical political move to centre the overlooked everyday lives of young, relatively privileged Indian-Australian residents affected by racial hierarchies, forced border crossings and mandatory hotel quarantine during the pandemic in Australian cities. I argue that their non-white and non-Anglocentric embodied gaze on coexistence in spacetimes of collective waiting, opens portals, shatters windows and crafts more breathable and just worlds that are relevant in a (post) Covid era. The article strengthens an ethical agenda of non-extractive learning by bringing Black, Brown, feminist and queer conceptualizations of worlds otherwise into conversation. What emerges are visualizations, encounters, experiments and fleeting solidarities in Australian quarantine hotels that intervene in the transformation of unjust worlds.

Background and Objectives: Sleep is a vital psychological function for health and well-being in all age groups, from children to adolescents, to adults and the elderly, and impacts quality of life. This study evaluated temporal changes in sleep quality and lifestyle behaviors among medical students in North-Western Romania (Transylvania) between the COVID-19 pandemic and the post-pandemic period. Materials and Methods: A cross-sectional design was employed involving 709 medical students assessed during the first pandemic wave (2020) and the 2023–2024 academic year. Online questionnaires collected data on demographics, body mass index (BMI), substance use, and physical activity. Sleep quality was measured using the validated Athens Insomnia Scale (AIS), and multiple linear regression was performed to identify predictors of sleep outcomes. Results: Post-pandemic data revealed a significant decline in sleep quality, with female gender and lower academic performance identified as significant predictors of insomnia symptoms (R2 of 0.258, p &lt; 0.05). While physical activity levels improved significantly in 2024 compared to the confinement period, this was accompanied by increased fast-food consumption and a rise in overweight and obesity rates. Conversely, illicit drug use decreased, and alcohol consumption patterns shifted, characterized by reduced weekly frequency among females but persistent binge drinking episodes. Conclusions: The transition to post-pandemic education yielded mixed health outcomes; while physical activity rebounded, sleep quality and nutritional status deteriorated. These findings highlight the necessity for university-based interventions focusing on sleep hygiene, nutrition, and stress management to support the well-being of medical students.

Understanding parental practices and attitudes towards vaccination is important to promote influenza vaccines among in-school children that can mitigate infection and spread of influenza. This study aimed to investigate influenza vaccination uptake, hesitancy and willingness among parents for their in-school children in the post-pandemic era of COVID-19 in South China. In April 2023, a cross-sectional survey was conducted to obtain a convenience sample of 3127 in-school children's parents in Shenzhen, China. Information about demographic characteristics, parent's psychological health status, child's health conditions, parent-reported influenza vaccination uptake, hesitancy and willingness among in-school children was collected. Binary logistic regression models were applied to detect parent-level and child-level associated factors of influenza vaccination uptake, hesitancy and willingness among parents. According to 3127 parents' report, the rate of influenza vaccination uptake within the recent 12 months for their in-school children was 57.6%, and 49.2% of parents reported vaccine hesitancy. Among 1326 parents of children who have not yet been vaccinated, 74.2% were willing to vaccinate their children in the future. The most reported obstacle for unwillingness was concerns about vaccine safety and side effects. Parent-level factors associated with parent-reported uptake, hesitancy and willingness of influenza vaccination included gender, education level, employment status, health perceptions (awareness of influenza vaccination and the free policy for students, perceived risk and worry about contracting influenza for the child) and perceived stress. Child-level factors included age, gender, history of previous influenza vaccination and history of vaccine allergy. Our study suggests that there is considerable room for Chinese parents to increase the uptake of influenza vaccination and eliminate vaccine hesitancy for in-school children. Multi-aspect efforts are needed to increase parental confidence and trust in influenza vaccination, in particular, based on parent-level and child-level associated factors.

Examining Suicidality in Youth With Disabilities: 2021-2023 National Survey on Drug Use and Health.

ABSTRACT Existing research on noncompliance with public health protocols during the Covid-19 pandemic features relatively low- rather than high-risk violations almost exclusively, with a small, difficult-to-verify set of exceptions. This paper adds an investigation of high-risk noncompliance with a qualitative inquiry into attendance at superspreader events in October 2020. With this possibly unique dataset, I use neutralization theory to analyze 27 college students’ decisions to attend indoor mass gatherings with at least 100 attendees. Using a new 60-neutralization model as a coding scheme, I find that, rather than using neutralizations independently, students knitted neutralizations together into a two-phase argument. Consistent with antisocial motivations for noncompliance documented in the literature, all but one argued they had a desire, right, and opportunity to attend parties. More than two-thirds, however, also explained measures they took to party safely in the hopes of ensuring no one was harmed. This is consistent with “creative non-compliance”: breaking a rule while acting parallel to its principles. This finding contributes to the literature on noncompliance during the Covid era, but also to new questions in neutralization theory regarding the new model’s exhaustiveness, whether neutralizers prefer higher-order neutralizations, and how identity and context influences which neutralizations are available to whom.

QT interval prolongation and its related factors before and after receiving lopinavir-ritonavir in the COVID-19 era: a historical cohort study.

This study aimed to evaluate national, demographic, and geographic trends in mortality associated with hypertension and ischemic heart disease (IHD) among U.S. adults from 1999 to 2023. Mortality data were extracted from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database. Adults aged ≥15 years with hypertension (ICD-10: I10-I15) listed as a contributing cause and IHD (ICD-10: I20-I25) as the underlying cause of death were included. Age-adjusted mortality rates (AAMRs) per 100,000 population and annual percent change (APC) were calculated using Joinpoint regression, stratified by year, sex, race/ethnicity, U.S. Census region, and urban-rural classification. Between 1999 and 2023, 3,575,793 hypertension-associated IHD deaths were recorded. The overall AAMR rose modestly through 2018 (APC = 0.4%; 95% CI, 0.1-0.6), sharply increased from 2018-2021 (APC = 10.3%; 95% CI, 7.7-11.9), and declined thereafter till 2023 (APC = -4.4%; 95% CI, -7.3 to -1.7). Men consistently exhibited nearly twice the mortality rate of women, and Black Americans experienced the highest AAMRs across racial/ethnic groups. Regionally, the South showed the greatest burden, while rural areas had approximately 20% higher mortality than metropolitan regions. Hypertension-associated IHD mortality in the U.S. demonstrates a U-shaped temporal pattern declining until the late 2010s, surging during the COVID-19 era, and only partially improving thereafter. Persistent disparities by sex, race, and geography underscore the urgent need for renewed, equitable prevention strategies targeting hypertension control and cardiovascular risk reduction nationwide.

This study presents a systematic review (SR) of the author’s research on distance learning (DL) during the COVID 19 pandemic, published between 2020 and 2024. As an author bounded corpus, it offers an exceptionally comprehensive, multi dimensional examination of DL during the COVID 19 pandemic, spanning every major dimension of the teaching learning process, thus offering one of the most extensive individual research programs on this topic in Saudi Arabia and beyond. The corpus consists of 30 studies that document the educational crisis, responses, adaptations, and outcomes across Saudi schools and universities during the pandemic period. The studies were organized into nine thematic clusters: digital infrastructure, technology use, and platforms; teaching practices and instructional strategies; student engagement and preferences; children, family role, and home based learning; psychological, social, and cultural dimensions; exams, assessment, and academic performance; curriculum adaptation; teachers’ professional development; and the pandemic job market for graduates. Results revealed an interconnected system of challenges and innovations. Digital inequity was a major issue during the early months of the pandemic, though it was mitigated through community based solutions. Instructors rapidly diversified their pedagogical practices by integrating podcasts, YouTube videos, blogging, mobile audiobooks, online vocabulary tasks, virtual speaking activities, and redesigned practicum practices. Students’ engagement patterns reflected both creativity and strain: while many benefited from interactive and technology mediated tasks, others experienced low self efficacy, anxiety, and a strong preoccupation with exams and grades. Studies on children highlighted the central role of parents in monitoring and supporting home based learning, as well as the benefits and risks of iPad use among young learners. Psychologically, the corpus revealed widespread dissatisfaction, low motivation, and emotional fatigue among students, alongside the potential of positive psychology and intercultural exchanges to enhance resilience. Assessment practices underwent some changes, resulting in flexible exam formats and grade inflation, while curricular structures remained largely unchanged due to institutional constraints. Only one study examined DL after the pandemic, indicating the need for further research on long term shifts in digital learning. Overall, the review demonstrates that DL during COVID 19 was not a uniform experience but a complex ecosystem shaped by infrastructure, pedagogy, learner agency, family dynamics, institutional policy, and socio emotional factors.

Female entrepreneurship continues to play a pivotal role in generating employment in the developing economies, particularly in the informal sector. There is, however, a paucity of empirical research on the impact of women-owned enterprises on gender-disaggregated informal sector work in South-eastern Nigeria. The research was conducted using a survey method, which gathered 500 female entrepreneurs. The effects of entrepreneurial activity, experience, financial assistance and capital on aggregate informal sector employment, male informal sector employment and female informal sector employment were estimated using ordinary least squares (OLS) regression. The results indicate that female entrepreneurship has a significant positive impact on informal sector employment in all three categories. There is also a positive and statistically significant effect of entrepreneurial experience, business capital and financial assistance on employment outcomes. This relationship between entrepreneurship and experience created a cohesive impact on employment among the women. The findings emphasise the significant contribution of female entrepreneurs to spreading employment in informal sectors, particularly in the recovery process after COVID-19. It is a study with policy implications that boosting entrepreneurial capacities among women could increase employment and economic sustainability in the area.

Out-of-pocket health expenditures and financial protection in Türkiye: pre-pandemic (2019) and COVID-19 era (2022) microdata.

Abstract Background Respiratory syncytial virus (RSV) is a leading cause of infant mortality and morbidity, yet national trends in RSV outcomes, particularly during the COVID-19 era, are not well defined. This study evaluated temporal patterns in RSV-related infant mortality and hospitalizations across the United States. Methods We analyzed RSV-associated infant mortality data from 2007–2022 using the CDC WONDER database and hospitalization rates from 2018–2025 using the hospitalization surveillance network (RSV-NET). Infant mortality and hospitalization patterns were assessed by season, race/ethnicity, and birth weight. Results Over 16 years, RSV-related infant mortality remained relatively stable, with no statistically significant year-to-year variation. Mortality rates were disproportionately higher among Black or African American infants and those with low birth weight. Seasonal hospitalization patterns varied substantially: the 2020–2021 RSV season recorded the lowest hospitalization rate, likely reflecting widespread COVID-19 mitigation measures, whereas the 2022–2023 season recorded the highest rate since 2018. Conclusion Although infant RSV mortality has remained stable, persistent disparities exist, and hospitalization rates show substantial seasonal fluctuations. These findings provide critical baseline data for assessing the impact of emerging RSV immunization strategies and highlight the need for targeted strategies to reduce persistent inequities in infant outcomes in the post–COVID-19 era. Impact RSV-related infant mortality in the United States has shown both stability and a sharp post-pandemic surge, with persisting disparities by sex, birthweight and race. This study integrates temporal, demographic, and geographic patterns to provide the national-level evidence of RSV mortality and hospitalization patterns among infants during COVID-19 era. These findings establish essential baseline estimates to evaluate effectiveness of preventive measures, while underscoring the urgency of targeted strategies to reduce disproportionate risks among vulnerable infants.

Background: Rheumatic heart disease (RHD) remains a major cause of preventable cardiovascular morbidity and mortality, particularly in low- and middle-income countries. Despite the World Health Organization’s 2018 resolution calling for the global elimination of RHD, substantial disparities in disease burden persist across regions and levels of socioeconomic development. Although previous studies have reported global trends, a clear comparative assessment of long-term changes in both fatal and nonfatal RHD burden across sociodemographic and geographic regions remains limited. This study aimed to assess long-term changes in the global burden of RHD between 1990 and 2021, with a focus on regional and sociodemographic disparities, using the most recent estimates from the Global Burden of Disease Study 2021. We additionally assessed temporal trends across sociodemographic index (SDI) groups and GBD regions, with a focus on fatal (years of life lost [YLL]) and nonfatal (years lived with disability [YLD]) components of disease burden. Methods: We conducted a secondary analysis of model-based estimates from the Global Burden of Disease Study 2021 to assess the burden of RHD between 1990 and 2021. Metrics included age-standardized and all-age incidence, prevalence, mortality, YLL, YLD, and disability-adjusted life years (DALYs). Data were stratified by 5 SDI levels and 13 global regions. Estimates were produced using DisMod-MR 2.1 and CODEm and are reported as means with 95% uncertainty intervals (UIs). Results: Globally, age-standardized mortality and DALY rates for RHD declined by 56% and 53%, respectively, from 1990 through 2021. YLL decreased by 59%, whereas YLD increased by 11%, indicating a shift toward chronic nonfatal burden. For example, the global age-standardized mortality rate decreased from 9.1 (95% uncertainty interval [UI], 8.4 to 9.8) to 4.0 (95% UI, 3.6 to 4.5) per 100,000. High- and high-middle–SDI regions achieved the greatest reductions across all indicators. In contrast, low- and low-middle–SDI regions experienced persistently high absolute deaths and DALYs, with South Asia accounting for more than 27% of global RHD deaths in 2021. Females consistently had a higher nonfatal burden (YLD) than males. Although the dataset includes the COVID-19 era, the specific impacts of the pandemic on RHD care and outcomes require further investigation. Across all SDI groups and regions, declines in DALYs were largely driven by reductions in YLL, whereas YLD remained relatively stable. Conclusions: Although global RHD mortality declined, substantial regional and socioeconomic disparities persist. The epidemiologic transition toward disability highlights the need for long-term care infrastructure, particularly for women, children, and low-SDI regions. Although based on modeled estimates, this analysis provides the best available insight into global RHD epidemiology and informs data-driven health policy and planning. Despite overall improvement, disparities remain between low- and high-SDI settings, underscoring the need for context-specific prevention and long-term management strategies.

Cardiovascular conditions such as cardiac arrest, arrhythmias, myocarditis, pericarditis, and pulmonary embolism (PE) contribute substantially to mortality. The COVID-19 pandemic introduced both direct (infection-related) and indirect (healthcare disruption) risks, potentially altering these trends. To assess the shifts in U.S. mortality from major cardiovascular causes before and after the COVID-19 pandemic, with emphasis on sex- and race-specific disparities. We analyzed national death certificate data from the Centers for Disease Control and Prevention-Wide Ranging Online Data for Epidemiologic Research Multiple Cause of Death database (2015-2023). Outcomes included cardiac arrest (I46), arrhythmias (I47-I49), myocarditis (I40-I41, I51.4), pericarditis (I30-I32), and PE (I26). Age-standardized mortality rates (ASRs) were calculated using the 2000 U.S. standard population. Rate ratios (RRs) for the post- versus prepandemic periods were estimated using Poisson regression, stratified by sex and race. Mortality increased across all outcomes in the postpandemic period. PE showed the largest relative rise (ASR: +31.4%; RR: 1.31, 95% confidence interval [CI]: 1.30-1.32), followed by myocarditis (+25.1%; RR: 1.25, 95% CI: 1.19-1.30), pericarditis (+21.4%; RR: 1.21, 95% CI: 1.19-1.24), and arrhythmias (+23.0%; RR: 1.23, 95% CI: 1.23-1.23). Cardiac arrest increased more modestly (+9.8%; RR: 1.09, 95% CI: 1.09-1.09). Men had consistently higher absolute rates, while Black and American Indian/Alaska Native populations experienced the steepest relative increases. The COVID-19 era was associated with sustained increases in U.S. cardiovascular mortality, particularly PE and arrhythmias. Disproportionate impacts among racial minorities highlight the urgent need for equitable access to preventive care, acute cardiovascular services, and long-term surveillance.

mRNA-based vaccines have demonstrated tremendous success during the era of COVID-19, but its therapeutic potential for treating cancer, especially poorly immunogenic solid tumors, remains largely underachieved. Herein, we report a class of self-adjuvanting α-helical polypeptides that can dramatically improve the antitumor efficacy of tumor neoantigen-encoding mRNAs. The α-helical polypeptides can facilitate the intracellular delivery of mRNAs into dendritic cells (DCs), simultaneously activate DCs by regulating NF-κB and IRF pathways, and improve the ability of dendritic cells to process and present mRNA-encoded neoantigens. Molecular docking and simulation results also confirm the stable complexation between mRNA and α-helical polypeptides. The conceived polyplex, upon subcutaneous administration, can migrate to the draining lymph nodes and transfect and activate DCs in the lymph nodes, resulting in superior neoantigen-specific cytotoxic T lymphocyte response in vivo. Compared to conventional lipoplexes or SM102 lipid nanoparticle-based mRNA vaccines that yield 0% tumor-free survival, the polyplex yields 83.3% and 33.3% tumor-free survival against E.G7-OVA lymphoma and 4T1 triple negative breast cancer, respectively, among the best antitumor efficacy reported to date for mRNA cancer vaccines. The polyplex also reprograms the immunosuppressive tumor microenvironment, by stimulating and enriching DCs, M1-phenotype CD86+ macrophages, and CD8+ T cells in the tumors. We also observed the upregulated expression of Programmed Death-1 (PD-1) by intratumoral CD8+ T cells and PD-L1 by 4T1 tumor cells after polyplex treatment and further demonstrated the synergistic effect between polyplex vaccine and anti-PD-1 therapy. Our polyplex system provides a facile and generalizable approach to developing robust mRNA-based cancer vaccines.