Search Results (241)

Background/Objectives: 23-valent pneumococcal polysaccharide vaccine (PPV23) effectiveness against community-acquired pneumonia (CAP) remains controversial, with critical gaps in low-coverage settings and beyond 5 years post-vaccination. We estimated real-world PPV23 effectiveness against CAP hospitalization and characterized its duration among elderly adults in a low-coverage region. Methods: A multicenter matched case–control study was conducted across 14 hospitals in Eastern China (2018–2022). Cases were patients aged ≥60 years hospitalized with clinically diagnosed CAP. Up to three controls per case were matched on sex, age (±3 years), admission date (±5 days), hospital, and residential community. Conditional logistic regression estimated vaccine effectiveness (VE), adjusting for chronic comorbidities and healthcare utilization. Results: Among 6645 cases and 15,806 controls, 5-year PPV23 coverage was 2.14% (cases) and 2.76% (controls). PPV23 was associated with a 22.5% reduction in CAP hospitalization (adjusted VE = 22.5%, 95% CI: 4.1% to 37.3%). Protection was concentrated in non-severe CAP (adjusted VE = 25.7%, 95% CI: 7.0% to 40.7%), with no significant effect in severe CAP (adjusted VE = −11.7%, 95% CI: −115.1% to 42.0%). Extending the exposure window to 6 years yielded no significant VE (adjusted VE = 17.3%, 95% CI: −1.8% to 32.8%). Conclusions: PPV23 provides meaningful protection against CAP hospitalization in elderly adults in low-coverage settings, only for non-severe disease. Waning efficacy beyond 5 years supports revaccination at that interval. Full article

Six years after the emergence of SARS-CoV-2, COVID-19 remains a dynamic public health challenge shaped by viral evolution, heterogeneous population immunity, changing vaccine strategies, and the long-term consequences of acute infection. Although the transition from pandemic emergency to endemic circulation has reduced the global burden of severe disease, COVID-19 continues to affect vulnerable populations, particularly older adults, frail patients, immunocompromised individuals, and subjects with multiple comorbidities. Vaccination has substantially modified the clinical course of infection, reducing hospitalization, intensive care admission, and mortality, while also reshaping surveillance priorities toward variant monitoring, vaccine effectiveness, waning immunity, breakthrough infections, and long COVID. At the same time, the pandemic has highlighted the need for integrated clinical risk stratification, including age, sex, frailty, inflammatory biomarkers, respiratory support requirements, and thromboembolic risk. Venous and arterial thrombotic complications have represented a key feature of severe COVID-19 and remain relevant for both acute management and post-discharge follow-up. This narrative review summarizes the main lessons learned from six years of COVID-19, focusing on epidemiology, vaccination campaigns, clinical risk assessment, thromboembolic complications, and surveillance strategies. Particular attention is given to the need for multidisciplinary and data-driven approaches capable of integrating virological, epidemiological, clinical, geriatric, and vascular medicine perspectives. Future COVID-19 surveillance should move beyond case counting and incorporate vaccine impact, population vulnerability, thrombotic and bleeding complications, long-term outcomes, and preparedness for emerging variants. Full article

Mumps remains a public health challenge worldwide despite being a vaccine-preventable disease. This review outlines the historical development and contrasting mumps vaccination policies in the United States and Japan and their epidemiological consequences. In the United States, where the two-dose measles, mumps, and rubella (MMR) vaccine is routinely administered, the incidence of mumps has markedly decreased. Recently, however, sporadic outbreaks have emerged, driven by breakthrough infections among vaccinated individuals. These resurgences are driven largely by waning immunity, coupled with antigenic divergence between the vaccine strain and circulating wild-type viruses. In contrast, Japan vaccination the MMR vaccine was licensed in 2026 after being suspended in 1993 owing to concerns over aseptic meningitis as an adverse event following immunization but mumps vaccination remains voluntary. This has resulted in low vaccination coverage, a lack of herd immunity, and recurrent epidemics. This review also highlights the disease-modifying effect of mumps vaccination, including a reduced risk of complications such as meningitis and orchitis, even in cases of breakthrough infection. In Japan, irreversible sensorineural hearing loss (mumps deafness), continues to occur even following subclinical infection. To prevent these complications, continuous molecular surveillance, improved vaccine safety, and reintroduction of routine two-dose mumps vaccination in Japan are essential. Full article

Botulinum toxin type A (BoNT-A) is an established treatment for cervical dystonia (CD), but objective neurophysiological markers across the injection cycle and between preparations are not well defined. We assessed afferent conduction (captured by CSP parameters), efferent conduction (captured by F-wave parameters) and clinical severity (TWSTRS) in 28 patients with caput-type cervical dystonia during waning (>14 weeks post-injection) and peak (4–6 weeks) phases, comparing onabotulinumtoxinA (ONA) and abobotulinumtoxinA (ABO). F-wave measures changed only modestly: F–M latency increased with ONA, while F-wave persistence decreased with ABO. In contrast, CSP measures consistently increased at peak in both groups (CSP end latency and CSP duration; both p ≤ 0.001). Overall, BoNT-A treatment phase is better reflected by CSP-derived inhibitory measures than by F-wave indices. TWSTRS improved at peak for both toxins, with no difference between ONA and ABO in clinical change (ΔTWSTRS p = 0.5514). Full article

Traumatic injury is one of the most common causes of disorders of consciousness (DoC) worldwide, but the management and prognosis of DoC remain enigmatic. The uncertainty surrounding the natural course of DoC, the tendency of consciousness to wax and wane, and a lack of effective treatments outside of avoiding additional insults renders trauma-associated DoC complex for both providers and patient surrogates to navigate. This review explores the acute clinical course of DoC after traumatic injury chronologically and aims to compile recommendations based on the current best practices for diagnosis, management, and prognostication when caring for these patients during their acute hospitalization. Updates from trauma and Traumatic Brain Injury (TBI) resources, such as the American College of Surgeons, as well as new recommendations in the field of DoC are summarized. Serial clinical assessment with a standardized neurobehavioral battery such as the CRSR-FAST remains the mainstay of clinical care and research for DoC. Accurate diagnosis, multifaceted management, and humility surrounding prognostic discussions are all critical to caring for patients with DoC after trauma. Most of the care for trauma patients with a DoC remains supportive and aimed at avoiding secondary insults while allowing time for the patient’s recovery. In the same way that clinical care focuses on a cycle of diagnosis, treatment, and prognosis with each providing insight for the next, ongoing and future DoC research will compound on itself and hopefully lead to more advances in the future. Full article

Aims: Murine studies show a promising effect of high-fiber β-glucan on glycemic control and serum lipids. In addition, β-glucan has recently been found to have strong antioxidant and immunomodulatory effects. Oat flakes are a natural source of β-glucan. However, the effects of oat flakes on glycemic variability, dyslipidemia, and pancreatic duodenum homeobox-1 (PDX-1) levels in type 1 diabetes (T1D) remain unclear. Hence, this study assessed the effect of oat flakes on glycemic variability, dyslipidemia, and PDX-1 among adolescents with T1D. Materials and Methods: Sixty adolescents with T1D were divided into 2 equally matched groups. Group A received oat flakes β-glucan 6 g per day for 3 months in addition to an ordinary diet and insulin regimen. Group B received an ordinary diet and insulin regimen. This was followed by crossing over both arms for another 3 months after a two-week washout period. All participants underwent auxological assessment, continuous glucose monitoring (CGM), hemoglobin A1c (HbA1c), fasting lipids, and PDX-1 measurements at baseline, 3 months, and 6 months. Results: Oat flakes consumption resulted in a significant decrease in the coefficient of variation, HbA1c, serum cholesterol, triglycerides, and LDL-C levels (p < 0.001), with a significant increase in TIR, HDL-C, and PDX-1 levels (p < 0.001). However, all these effects waned after the stoppage of the oat flakes, except for HDL-C. Conclusions: Oat flakes have a favorable outcome on glycemic metrics, lipid profile, and PDX-1 in adolescents with T1D. Full article

Background: Invasive meningococcal disease (IMD) remains a rare but severe condition associated with high mortality and a significant risk of long-term sequelae. Despite global vaccination efforts, the epidemiology of Neisseria meningitidis continues to evolve, with serogroup B (MenB) representing the predominant cause of IMD in many high-income countries. Methods: This consensus document reviews current evidence on MenB epidemiology and the role of the multicomponent meningococcal serogroup B vaccine (4CMenB), with a focus on immunogenicity, strain coverage, real-world effectiveness, and remaining challenges. Results: Protein-based MenB vaccines have overcome the limitations of polysaccharide approaches, demonstrating robust immunogenicity across age groups. Real-world data confirm substantial vaccine effectiveness, particularly in infant immunization programs and outbreak settings, with significant reductions in disease incidence. For example, in England in the 3 years after vaccine introduction, MenB IMD incidence declined by 75% in immunized infants compared to unvaccinated controls. Adjusted vaccine efficacy was 52.7% after the two-dose primary series and 59.1% following the booster dose, highlighting the contribution of the booster. However, protection is influenced by antigenic variability among circulating strains, resulting in incomplete and geographically variable coverage. In addition, antibody waning over time and the limited impact on nasopharyngeal carriage reduce the potential for long-term and indirect protection. These factors highlight the need to optimize vaccination strategies, including the timing of booster doses, particularly in adolescents, and the role of vaccination in different epidemiological contexts. In this regard, it is not precisely defined whether infants who were immunized in the first year of life need a booster dose in the preschool period, especially in countries with a high incidence of MenB disease. Moreover, it is not established whether and when adolescents who were vaccinated both in infancy and during the preschool period need a booster dose. Economic considerations and variability in national immunization policies further contribute to heterogeneity in vaccine implementation. Emerging evidence suggests possible cross-protection against other meningococcal serogroups and Neisseria gonorrhoeae, although findings remain inconsistent across different risk groups and do not allow us to recommend 4CMenB vaccine beyond MenB IBD prevention. Conclusions: 4CMenB is an effective tool for preventing MenB IMD, although further studies are needed. Future strategies should prioritize age-targeted boosting and enhanced genomic surveillance to maximize impact. Full article

Enterovirus D68 (EV-D68) is a non-polio enterovirus that can cause a polio-like paralysis condition, acute flaccid myelitis (AFM). EV-D68-associated AFM cases waned in the US after 2018, and the reasons for this are unknown. It has recently been demonstrated that EV-D68 containing point mutations in viral structural proteins VP1 and VP3 resulted in decreased paralysis in different neonatal mouse models. However, phenotypes of these mutations in a human multicellular central nervous system (CNS) model are unknown. We hypothesize that mutations in VP1 and VP3 will similarly direct neurotropism in human spinal cord organoids (hSCOs). To investigate this, we recreated viruses with mutations in VP3 (I88V) or VP1 (L1I/N2D/T98A/E283K or L1P/V148A/K282R) and infected hSCOs. We found that VP3 I88V and VP1 L1I/N2D/T98A/E283K resulted in decreased titer and viral protein staining, consistent with attenuated neurovirulence in previously published murine models. We also found through immunofluorescence that VP1 L1P/V148/K282R mutations altered cellular tropism, primarily infecting glial cells rather than neuronal cells. When these mutations were combined, their effects on neurotropism were not additive. Sequence analysis of recently circulating EV-D68 strains reveals that VP3 I88 and VP1 E283 have remained the dominant amino acid residues since 2014, whereas VP1 sites 1, 2, and 98 have higher population diversity, indicating that these residues may be contributing to newly reduced neurovirulence after 2018. Full article

Background: Since China incorporated the hepatitis B vaccine into its Expanded Program on Immunization (EPI) in 2002, the first cohort of infants to receive the full vaccination series has now reached college age. As vaccine-induced antibodies gradually wane, this cohort faces a higher risk of infection. Therefore, we assessed their current seroprotection status and evaluated the immunogenicity and short-term antibody kinetics of a single 60 μg booster dose in susceptible individuals, while also constructing a model of expected duration of protection. Methods: In a multicenter study across three Anhui universities, 2988 students were screened for HBV markers. Among them, 160 who tested negative for all five markers received a single 60 μg booster. Antibody titers were monitored for 1–5 months. Results: Serological screening showed 0.33% HBsAg positivity, 36.28% anti-HBs positivity, and 63.02% negativity for all markers, indicating high susceptibility. After the booster, seroprotection rate (SPR) remained >85% throughout follow-up, and anti-HBs geometric mean concentration (GMC) peaked at 1–2 months. Stratified analysis based on immune response status revealed that the proportion of high responders (≥100 mIU/mL) peaked early and then gradually declined, whereas the proportion of low responders (10–99.99 mIU/mL) increased over the follow-up period. A linear mixed-effects model predicted that protective levels (anti-HBs ≥10 mIU/mL) would persist for an average of 32.8 months. Conclusions: A substantial proportion of university students lack protective immunity against hepatitis B. A single 60 μg booster rapidly and effectively induced protection, demonstrating strong immunogenicity. These findings support implementing efficient booster strategies in university settings. Full article

Background: Measles remains a global public health threat despite the availability of an effective vaccine and substantial progress toward elimination in many countries. Outbreaks in highly vaccinated settings suggest that waning vaccine-induced immunity, particularly among adults, may create silent susceptibility gaps capable of sustaining viral transmission. Aim: To evaluate age- and cohort-specific patterns of measles-specific antibody levels in Mexican adults and to examine evidence suggesting lower vaccine-induced antibody levels in younger vaccinated cohorts. Methods: A cross-sectional seroepidemiological study was conducted among 302 voluntary blood donors aged 18–70 years. Demographic, clinical, and vaccination data were collected through structured interviews. Serum anti-measles-virus (MV) IgG levels were quantified using a commercial ELISA. Antibody concentrations were analyzed according to age, sex, vaccination history, self-reported measles infection, and historical vaccination strategies. Multivariate linear models were applied to identify factors associated with IgG levels. Results: Anti-MV IgG seropositivity (>200 mIU/mL) was 67.2%, with a geometric mean concentration (GMC) of 270.43 mIU/mL. A positive correlation was observed between age and antibody levels (r_s = 0.161, p = 0.005). Individuals born before the introduction of the measles vaccine (pre-1970) had significantly higher GMCs (1096.63 mIU/mL) than younger cohorts. A history of natural infection tended to be associated with higher antibody levels (GMC: 428.38 vs. 257.24 mIU/mL; p = 0.051). In multivariate analysis, historical vaccination strategy emerged as the primary factor associated with antibody levels, whereas age alone was not significant. Conclusions: Cohort-specific differences in measles IgG levels suggest generational patterns of immunity and are consistent with diminished vaccine-induced antibody levels in younger adults in the absence of natural boosting. These findings highlight the importance of ongoing serological surveillance in post-elimination settings and underscore the need for targeted public health interventions. Full article

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection in infants and young children worldwide and continues to impose a substantial disease burden despite recent advances in preventive strategies. Natural infection does not confer durable protective immunity, resulting in repeated reinfections, with the most severe disease occurring during early infancy. This review examines antibody-mediated prevention of RSV infection, with particular emphasis on vaccine development and maternal immunization. We reviewed current evidence on RSV pathogenesis, immune evasion, and antigenic characteristics relevant to vaccine design, focusing on viral surface glycoproteins targeted by preventive strategies. Recent data on licensed vaccines, long-acting monoclonal antibodies, and maternal immunization approaches were also evaluated. The RSV fusion (F) glycoprotein is the principal target of neutralizing antibodies and underpins currently licensed vaccines and monoclonal antibody products. Although circulating RSV strains show gradual antigenic evolution, primarily in the attachment protein, the F protein remains relatively conserved, resulting in only modest reductions in neutralization by human polyclonal sera over time. Constrained evolution of the F protein likely contributes to the sustained effectiveness of F-based interventions. However, waning F-specific neutralizing antibody titers contribute to susceptibility to reinfection, underscoring the importance of passive immunization strategies during early life. Maternal vaccination and long-acting monoclonal antibodies represent key advances in protecting young infants against RSV, but challenges remain in achieving equitable global implementation. Continued evaluation of antigenic evolution, the durability of protection, and optimization of maternal and infant immunization strategies will be critical for long-term disease control. Full article

China’s dual pursuit of a “Digital China” and its carbon-neutral goals has driven a coordinated strategy of digitalization and green transformation. Yet the extent to which firms have realized this synergy—and its effect on total factor productivity (TFP)—remains underexplored. Using panel data from 2011 to 2025 on all A-share listed companies, we construct a composite index of digital–green coordination and estimate firm-level TFP via the Levinsohn–Petrin method. Employing fixed-effects panel regressions and mediation analyses, we find the following: (1) the digital–green synergy significantly enhances TFP growth, with robustness confirmed across alternative measures, propensity score matching, city fixed effects, and instrumental variable approaches; (2) this effect is stronger for non-SOEs and firms with higher baseline TFP and exhibited an “inverted-U” pattern over China’s 13th and 14th Five-Year Plans; (3) corporate social responsibility (CSR), cost stickiness reduction, and green technological innovation each mediate this relationship—CSR and cost stickiness play larger roles in SOEs, while green innovation mediates across all firm types and TFP levels, also showing an “inverted-U” temporal trend; and (4) over time, CSR’s mediating effect wanes in the 14th Five-Year period, cost stickiness mediation gradually declines, and green innovation mediation is continually strengthened. These findings provide evidence of the association between digital–green alignment and firm productivity in China, using an index that summarizes the joint orientation toward digitalization and greening. Full article

Introduction: Cholera remains a major public health threat in endemic settings, and oral cholera vaccine (Shanchol™) campaigns are increasingly used amid constrained global supply. However, practical decisions on revaccination require clearer, setting-specific estimates of how rapidly vaccine-induced vibriocidal antibodies peak and wane. Methods: We conducted a prospective cohort kinetics analysis in Lukanga Swamps (Central Province, Zambia), enrolling adults (18–65 years) stratified by prior Shanchol™ exposure (0, 1, or 2 previous doses). All participants received two Shanchol™ doses 14 days apart, with serum collected at baseline and days 14, 28, 60, and 90 (end of follow-up). Ogawa and Inaba vibriocidal titres were measured using a complement-based assay and analysed on the log10 scale. Serotype-specific mixed-effects models with natural cubic splines for time (knots: 14, 28, 60 days) assessed trajectories by prior-dose strata, adjusting for age, sex, and HIV status. Peak timing and post-peak half-life were derived from model-based predictions with participant-level bootstrap CIs (1000 replications). Results: The analysis included 225 participants: 68 (30.2%) with zero prior doses, 89 (39.6%) with one, and 68 (30.2%) with two; median age was 33 years (IQR 25–49), 56.4% were female, and 19.2% were HIV-positive. Modelled titres for both serotypes rose steeply after vaccination, peaking around day 36–37 across prior-dose strata. Ogawa titres reached half of peak by about day 73–78, corresponding to post-peak half-lives of 37–41 days; Inaba declined more slowly with half-lives of 42–46 days. Confidence intervals overlapped across prior-dose strata, indicating minimal differences by vaccination history. Conclusions: In this cholera-endemic adult population, Shanchol™ induced vibriocidal responses that peaked at ~5 weeks and waned over the following 5–7 weeks, with broadly similar kinetics regardless of prior vaccination and slightly slower decay for Inaba than Ogawa. These parameters can inform booster timing in hotspot settings. Full article

Foreign direct investment (FDI) has often been cast as a straightforward engine of growth, yet its record across Central and Eastern Europe tells a more tangled story where outcomes hinge on the interplay of education, governance, and the timing of external shocks. This study embeds fixed effects panel econometrics within a systems framework, treating FDI as a subsystem of socio-economic dynamics. Using a long-run panel of eleven economies from 2000 to 2023, the analysis models path dependence and regime shifts through interaction terms and period-specific dummies set against a systems-thinking backdrop. The analysis shows that for the average CEE economy, FDI’s contribution has waxed and waned: it dragged on growth during the early transition years (2000–2007), settled into a neutral role after the global financial crisis, and proved unpredictable in the pandemic era. Romania stands out, however, with a marked “FDI premium” quantified as approximately 0.7 pp of growth per pp of FDI that seems to stem from reinforcing loops between rising tertiary enrolment and productivity spillovers. Mapping these feedbacks brings to light virtuous circles where human capital and resilience make or break the benefits of foreign capital. The policy message is plain: nurture the positive loops through investment in skills and firm linkages, keep institutions nimble enough to adapt, and watch for early warning signs of systemic strain. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative condition with a multifactorial etiology, characterized by dopaminergic neurons being selectively absent in the midbrain. Clinically, PD manifests primarily with core motor symptoms of resting tremor, bradykinesia, and muscle rigidity, and is often accompanied by non-motor symptoms including depression, cognitive impairment, and gastrointestinal dysfunction. Among the extensive relevant research, few have explored the precise pathogenic mechanisms underlying PD, and no curative treatment is available. Current pharmacological therapies mainly provide symptomatic relief by enhancing central dopaminergic function or modulating cholinergic activity; however, their long-term efficacy is frequently constrained by waning therapeutic response, drug tolerance, and adverse reactions. Accumulating evidence suggests that several naturally derived neuroactive compounds—such as gastrodin, uncarin, and paeoniflorin—demonstrate significant potential in combating PD. In this systematic review, we examined original research articles published from 2010 to 2025, retrieved from PubMed, Web of Science, and CNKI databases, using predefined keywords of Parkinson’s disease, neuroprotective herbal compounds, traditional medicine, multi-target mechanisms, natural product, autophagy, neuroinflammation, and oxidative stress. Studies were included if they specifically investigated the mechanistic actions of natural compounds in PD models. Conference abstracts, review articles, publications not in English or Chinese, and studies lacking clearly defined mechanisms were excluded. Analysis of the available literature reveals that natural neuroactive compounds may exert anti-PD effects through multiple mechanisms, e.g., inhibiting pathological α-synuclein aggregation, attenuating neuronal apoptosis, suppressing neuroinflammation, mitigating oxidative stress, and restoring mitochondrial dysfunction. This review provides insights that may inform the clinical application of natural bioactive compounds and guide their further development as potential therapeutic candidates against PD. Full article