Search Results (1,494)

Vitamin D has been linked to beneficial effects across more than 100 health outcomes, generating substantial interest in its extraskeletal functions. However, because nutrients differ fundamentally from pharmaceuticals in biology and mechanisms of action, conventional pharmaceutical-style randomized controlled trials (RCTs) are often inappropriate for evaluating nutrient efficacy. Instead, well-designed observational studies that have assessed serum 25-hydroxyvitamin D [25(OH)D] concentrations and correlated them with biologically relevant clinical outcomes provide evidence of effectiveness and establish causality. Since vitamin D primarily acts as a preventive agent for chronic diseases, the strongest evidence is derived from large, long-term, ecological and prospective cohort studies. In contrast, many RCTs have failed to demonstrate significant benefits because of methodological limitations, including enrollment of vitamin D-sufficient participants, inadequate dosing regimens, vitamin D supplementation in control groups, short intervention periods, and analyses based on assigned dose rather than serum 25(OH)D concentrations achieved, which determine biological responses. Early ecological studies demonstrated inverse associations between solar ultraviolet B doses and the risks of cancer, cardiovascular disease (CVD), and infectious diseases. These findings have been consistently supported by numerous prospective larger cohort studies linking higher serum 25(OH)D concentrations with improved health outcomes. Observational studies also offer important advantages, including being large and covering diverse populations, wide variations in vitamin D status, longer follow-up, and adjustment for multiple confounding factors. When interpreted within a biological framework using Bradford Hill’s criteria for causality—including consistency, strength and temporality of associations, dose–response relationships, biological plausibility, mechanistic evidence, coherence, and experimental support—the accumulated evidence strongly supports causal relationships that vitamin D sufficiency reduces risks of several diseases. This narrative review critically evaluates the evidence for cancer, CVD, blood pressure, COVID-19, type 1 and type 2 diabetes, periodontal disease, multiple sclerosis, and dementia. For these diseases, the authors concluded that the evidence satisfies Hill’s criteria for causality and aligns with current understanding of vitamin D biology and nutrient–health relationships. Full article

Background: In the wake of the COVID-19 pandemic, nursing students and educators are navigating an increasingly complex academic environment. The rigorous demands of nursing education, combined with diminished academic preparedness and growing mental health concerns, have heightened the need for effective wellness interventions. The SKY Happiness Retreat©, an evidence-based program incorporating breathwork, meditation, and mindfulness practices, offers a potential strategy to enhance student resilience and reduce stress. Purpose: This pilot study examined the impact of integrating the SKY Happiness Retreat© into a Bachelor of Science in Nursing (BSN) program. This study evaluated whether participation reduced perceived stress and improved students’ ability to manage stressful situations. Methods: A quasi-experimental pretest–post-test design was used with junior-level BSN students recruited through convenience sampling at a rural university. Participants completed a structured three-day retreat focused on breathwork, meditation, and mindfulness. Outcomes were measured using the Mood and Anxiety Symptom Questionnaire (Mini-MASQ), the Perceived Stress Scale (PSS), and the Brief Resilience Scale (BRS). Results: Perceived stress significantly decreased following the intervention (PSS: pre M = 18.50, SD = 4.583; post M = 17.30, SD = 5.841; t(43) = 2.072, p = 0.022). General distress also significantly improved (Mini-MASQ: pre M = 15.51, SD = 6.535; post M = 12.82, SD = 5.118; t(44) = 3.941, p < 0.001). No significant changes were observed in anxious arousal or anhedonic depression. BRS scores demonstrated a modest increase in resilience. Conclusions: The SKY Happiness Retreat© shows promise as an experiential learning strategy within undergraduate nursing education. Findings suggest participation was associated with reductions in perceived stress and general distress while promoting resilience. Integrating evidence-based wellness programs into prelicensure nursing curricula may better prepare students to manage academic and professional stress. Larger, longitudinal studies are needed to evaluate long-term effectiveness. Full article

Influenza A(H1N1)pdm09 remains one of the predominant seasonal influenza viruses worldwide and continues to evolve under the combined effects of host immunity, vaccination, and changing epidemiological conditions. However, the long-term impact of the COVID-19 pandemic on its evolutionary dynamics remains poorly understood. We investigated the genetic variability and phylodynamic evolution of the hemagglutinin (HA) and neuraminidase (NA) genes of Italian A(H1N1)pdm09 viruses collected between 2009 and 2026. Time-calibrated phylodynamic analyses, Bayesian Skyline Plots (BSPs), Lineages Through Time (LTT) graphs, principal component analysis (PCA), and codon-based selection analyses were used to characterize long-term evolutionary patterns. Both HA and NA followed continuous evolutionary trajectories, with a marked post-2020 genetic shift associated with the emergence of 6B.1A.5a.2-related clades. HA showed greater evolutionary variability than NA, whereas selection analyses identified only one positively selected site in HA and none in NA, consistent with reduced adaptive diversification in recent strains. Phylodynamic analyses revealed a marked decline in effective population size and lineage accumulation during the COVID-19 pandemic, followed by renewed expansion after 2022. Overall, Italian A(H1N1)pdm09 viruses exhibited reduced genetic diversity, limited evidence of positive selection, and coordinated genomic restructuring following the pandemic. These findings provide new insights into the long-term evolutionary dynamics of A(H1N1)pdm09 in Italy and reinforce the importance of sustained genomic surveillance for anticipating evolutionary changes and informing evidence-based public health strategies. Full article

Agricultural technological innovation is essential for sustainable agricultural modernization and rural development. However, agricultural technology enterprises often face persistent financing constraints because research and development (R&D) activities involve long investment cycles, high uncertainty, and delayed returns. Using a firm-level panel dataset of Chinese agricultural technology enterprises, this paper examines the effect of relational patient capital (RPC) on agricultural technological innovation by employing a two-way fixed-effects model. The results show that RPC significantly promotes agricultural innovation output. Mechanism analysis indicates that RPC enhances innovation through two channels. First, it facilitates firms’ digital transformation, thereby reducing R&D uncertainty and organizational costs. Second, it alleviates financing constraints by stabilizing cash flows to support R&D investment. The results remain robust after clustering standard errors, excluding the years affected by the COVID-19 pandemic, and employing lagged specifications. Heterogeneity analyses further reveal that the positive effect is more pronounced among small-scale enterprises and firms located in central and eastern China, where financing frictions and resource constraints are relatively more severe. By linking RPC to firm-level agricultural innovation, this study extends the literature on agricultural finance and innovation financing, highlighting the role of long-term, relationship-based capital in addressing market failures in agricultural R&D. The findings suggest that rural financial policies should encourage stable, long-term investment, strengthen financing support for small agricultural technology enterprises, and integrate patient capital with digital transformation initiatives to promote sustainable agricultural and rural development. Full article

This study examines the long-run relationship between terms of trade (TOT) and real fishing-sector GDP in a small open economy, focusing on the Peruvian case. Despite the strategic importance of fisheries for exports, employment and foreign exchange generation, the extent to which external price conditions are associated with fishing-sector performance remains insufficiently explored in sector-level research. Building on the notion that TOT summarise opportunities and constraints arising from the international environment, the paper evaluates whether persistent external conditions are linked to the long-run trajectory of the fishing sector. The analysis employs the Johansen cointegration approach and a bivariate Vector Error Correction Model (VECM) using quarterly data for the period 2001–2025. Seasonal effects are incorporated through quarterly dummy variables, while robustness is assessed by controlling for extreme El Niño–Southern Oscillation (ENSO) episodes and the COVID-19 pandemic. The results reveal the existence of a unique long-run equilibrium relationship between TOT and fishing-sector GDP. The error-correction mechanism indicates that deviations from equilibrium are actively corrected over time, whereas the adjustment coefficient for TOT is statistically insignificant. Robustness tests further show that El Niño episodes are negatively and significantly associated with short-run sectoral performance, while no statistically significant association is detected for La Niña. The COVID-19 control does not materially alter the long-run relationship identified by the model. The findings contribute sector-level evidence for a resource-dependent economy and suggest that long-run equilibrium and sectoral adjustment dynamics are important elements for understanding the long-run behaviour of the fishing sector. Full article

In May 2025, a new and welcome Pandemic Treaty was signed. The success of this treaty for the management of future pandemics depends on a re-evaluation of the importance of previous well-established treaty-based international human rights norms in controlling health crises. During the COVID-19 pandemic, public health responses globally were characterised by poor preparation, uncertainty, and hasty and sometimes perverse decisions. International human rights norms, especially health rights, and other treaty obligations were honoured more in their breach than their observance. The lessons learned from public health strategies that had integrated international human rights norms into the control and management of the HIV/AIDS pandemic were either ignored or forgotten. Early public health attempts to control the HIV/AIDs pandemic were hobbled by data breaches, travel restrictions, compulsory reporting, stigma, and misinformation about how the virus spread. This was replaced by a more successful human rights-based approach (HRBA) that used health rights indicators to identify groups susceptible to the disease but difficult to reach with conventional public health policies. The efficacy of health rights indicators and HRB methodology to remove barriers to treatment and suppress pandemics should have been seriously considered in strategies to control COVID-19. The article claims that failure to do this meant that more lives were lost than necessary and more people were left with serious long-term health effects. This article explores the practical significance of the international human rights legal framework, especially health rights, as trialled during the HIV/AIDS pandemic, for the management of COVID-19 and other pandemics. Full article

The housing sector is an important pillar of the economy. Understanding the trend and factors influencing it is essential for effective policy formulation and purchasing decisions. The objectives of this study are to assess the performance trajectory of the Australian housing market and to identify key macroeconomic factors influencing it over the past two decades. The presence of structural shifts in the housing market due to changing economic conditions highlights the importance of examining both short-run adjustments and long-run equilibrium relationships; however, limited recent studies have investigated these evolving dynamics, which this study addresses by employing the cointegration and Vector Error Correction Model (VECM). Empirical findings indicated the dynamics of previous period RPPI, interest rates, population growth, COVID-19 dummy, and adjustment components (ECT) are affecting housing market dynamics but with effects varying across different lag periods. On the other hand, the long-run estimates reported variables including population growth, the COVID-19 pandemic, household income, and unemployment rate have a significant impact on RPPI at the 5% significance level. The finding of the error correction model suggests a gradual adjustment of short-term deviation with ECTt-1 = −0.078 towards the long-term equilibrium quarterly. To further validate the robustness of the results, an Impulse Response Function (IRF) analysis was performed. The empirical findings are valuable as they provide insights that assist policymakers in formulating housing policies and support investors and purchasers in making informed decisions. Full article

The SARS-CoV-2 virus has infected approximately 778 million people worldwide since the pandemic. Patients who have survived coronavirus disease (COVID-19) may experience long-term symptoms related to cognitive deficits, mood changes, and depressive disorders. The mechanisms underlying the long-term effects of COVID-19 on the brain are being actively investigated. SARS-CoV-2 infection triggers various mechanisms, such as hyperstimulation of the immune response, which may lead to changes in the central nervous system. In this article, we review the evidence linking COVID-19 to neurodegenerative disorders and cognitive impairment. Current research indicates that patients with pre-existing cognitive and neuropsychiatric deficits have a poorer prognosis after SARS-CoV-2 infection, and patients who have survived COVID-19 may be at increased risk of developing dementia and mood disorders. We analyse the available evidence regarding SARS-CoV-2 brain infection, induction of inflammation, coagulopathy, and blood–brain barrier (BBB) dysfunction as possible mechanisms underlying the disorders in the acute phase of COVID-19 disease and contributing to the development of neurodegenerative disorders in long COVID. Viral infection can trigger inflammation of the central nervous system (CNS), leading to damage and contributing to the development of cognitive dysfunction. Full article

The transition to a circular economy (CE) presents significant financial challenges and opportunities for public waste management and fiscal governance in Slovakia. This study examines the financial implications of the circular economy transition for public expenditure related to municipal waste management in Slovakia using national-level aggregated data. Unlike previous studies that primarily focus on environmental performance, this research develops an integrated empirical framework combining environmental, financial, and governance indicators to evaluate the fiscal implications of the CE transition. A multivariate regression model was estimated using national environmental statistics, national financial data, and waste management indicators. The model demonstrated good explanatory performance (adjusted R² = 0.842; F = 15.87, p < 0.001). The results indicate that resource recovery, environmental investment, and CE policy implementation are significantly associated with municipal waste management expenditure, while the COVID-19 period was associated with higher expenditure. The findings suggest that although the CE transition requires substantial initial investment, effective resource recovery and appropriate public financial governance may contribute to the long-term fiscal sustainability of municipal waste management systems. The study provides evidence that may support policymakers and public authorities in developing evidence-based budgeting, more effective investment planning, and financially sustainable implementation of circular economy policies in Slovakia. Full article

Caused by the SARS-CoV-2 virus, the COVID-19 pandemic is still considered a complex challenge, with manifestations not only of respiratory issues, but also conditions related to chronic cerebrovascular damage. Endothelial biomarkers, neuropathological and neuroimaging findings indicate endothelial dysfunction, microthrombosis, and disruption of the blood–brain barrier (BBB) are central mechanisms for acute and chronic ischemic and hemorrhagic cerebral events. Understanding these mechanisms is vital to reducing their impact on population health, whether through treatment or prevention of adverse outcomes. The objective of this study is to perform a review of the scientific literature on the post-infection effects of SARS-CoV-2 affecting the cerebral endothelium and the BBB, correlating them with potential clinical outcomes. Material and Methods: Analysis of studies extracted from the PubMed database using the following terms: Long-COVID “AND” SARS-CoV-2 “AND” blood–brain barrier. Inclusion criteria: keywords, publications related to the topic, and primary studies published after peer review. Exclusion criteria: preprint studies, publication outside of the timeframe 2020–2025, study design not compatible with this research, and full text not available. Results: An initial 121 studies were identified, of which 105 were excluded due to not meeting all inclusion criteria and 6 studies were inaccessible due to not being in the English language and full-text access limitations. Fifteen articles were included in the analysis, for topics as expression of viral receptors in the endothelium, markers of their activation, cerebral microvascular injury and coagulopathies. To clarify the pathogenic cascade, the evidence was stratified by biological model where in vitro evidence demonstrates that the Spike protein induces direct endothelial toxicity and platelet aggregation, establishing the primary molecular insult. Animal models confirm the translation of this insult into structural degradation of the BBB and pericyte loss. Clinically, infection-phase findings, characterized by multifocal microthrombosis and permeability spikes, act as the determining event that predisposes to the persistent neuroinflammatory environment. Biomarkers of BBB disruption and neuronal damage were consistently reported, with persistence of BBB dysfunction modifying risk stratification and rehabilitation efforts. Reported cases of Long-COVID demonstrated normalization of BBB markers without correlation with long-term symptoms, suggesting that other mechanisms are involved in Long-COVID. Conclusion: Cerebral endotheliopathies and BBB dysfunction in patients with COVID-19 continue to impact the health of the population. The scientific literature indicates that SARS-CoV-2 induces cerebral endothelial injury, BBB disruption, and an increased risk of vascular events related to endotheliopathy, inflammation, and hypercoagulability. Understanding the impact of COVID-19 pathology on the population and developing prospective studies is essential to quantify the prevalence and mechanisms of brain injury. The identification of molecular targets and infection pathways are promising toward defining both preventive and therapeutic strategies to improve outcomes in the Long-COVID population. Full article

SARS-CoV-2 infection leads to extrapulmonary complications in multiple organs, including the brain, both in the short-term and long-term. The neurological manifestation of SARS-CoV-2 infection ranges from benign signs like loss of smell and loss of taste to severe complications like encephalitis, stroke, and exacerbation of Alzheimer’s disease (AD) progression. Pericytes are mural cells of the brain vasculature that help maintain the blood–brain barrier (BBB), regulate cerebral blood flow (CBF), modulate neuroinflammation, and clear toxic materials, including amyloid beta. Pericytes express ACE2, the receptor for SARS-CoV-2, and therefore may be targeted by either direct virus infection or virus-induced inflammatory cytokines induced by the virus in the brain. To further study the effects of SARS-CoV-2 on pericytes and BBB integrity, the long-term effects of SARS-CoV-2 infection on brain pericytes, inflammation, and other neuropathological complications were analyzed in mice. K18 (human ACE2 transgenic) mice were infected with 10³ PFU of SARS-CoV-2 (delta strain), and the brains were analyzed at 6, 14, and 30 days post-infection (dpi). A significant reduction in the weight of infected mice was observed by 6 dpi. Viral nucleocapsid protein and infectious SARS-CoV-2 were observed in the brains of all mice by 6 dpi, and in some mice by 14 dpi, but not at 30 dpi. This observation suggests viral neurotropism with subsequent clearance at later timepoints. Despite virus clearance, the levels of inflammatory mediators, including TNF-α and IFN-γ were significantly elevated up to 30 dpi. We also observed a significant reduction in the level of brain pericytes by 14 dpi up to 30 dpi. Importantly, an increase was observed in the level of Friend Leukemia Integration 1 (FLI-1), a transcription factor known to promote pericyte cell death, from 14 dpi up to 30 dpi. The level of amyloid beta 1–42 was elevated in the brain of infected mice at 6 dpi, and this was maintained up to 30 dpi, and there was a decrease in neuronal density from 14 to 30 dpi. Furthermore, we observed an increased expression of Alzheimer’s disease (AD)-associated genes like PSEN1, BACE1, and APP. Furthermore, there was increased activation of several neurodegenerative pathways, including “G alpha (z) signaling pathway”, “Apelin muscle signaling pathway”, and “G beta-gamma (Gβγ) signaling”, in the brains of infected mice compared to control mice. Collectively, the observed neuropathology and unique molecular markers of neurodegenerative disease progression provide a novel mechanism by which COVID-19 may promote dementia/AD by contributing to pericyte loss and BBB dysfunction during infection. Full article

Background/Objectives: Federated electronic health record networks are increasingly used for real-world evidence generation, but publication-use patterns for TriNetX remain incompletely characterized. This study mapped Web of Science-indexed articles that explicitly mentioned TriNetX and examined their distribution across clinical domains and study purposes. Methods: We searched the Web of Science Core Collection for articles published during 2018–2025 with “TriNetX” in the title, abstract, or author keywords. Bibliometric indicators, journal sources, citation impact, author-keyword co-occurrence, and trend topics were analyzed using R, bibliometrix, Biblioshiny, and VOSviewer. A reproducible rule-based dictionary classified clinical domains and study purposes, and a supplementary Scopus analysis assessed pattern-level reproducibility. Results: The corpus included 1573 articles. Annual output increased from 1 article in 2018 to 871 in 2025. Corresponding-author output was concentrated in the United States and Taiwan. Highly cited studies were dominated by COVID-19 research. Keyword analyses suggested a shift from pandemic-related topics toward mortality, cardiometabolic disease, and medication-related outcomes. Domain–purpose mapping showed that risk/prognosis studies were most common, whereas effectiveness, health services, and method/validation studies were less frequent. Scopus validation reproduced the main annual, source-level, and domain–purpose patterns. Conclusions: TriNetX-based publications expanded rapidly and diversified across clinical fields. Domain–purpose mapping shows where research has concentrated and where it remains sparse; lower frequency, however, should not be read as a definitive clinical evidence gap, since some areas may be less suited to the platform. Where the network is well suited, future work could give greater attention to comparative effectiveness, long-term safety, care pathways, and phenotype validation. Full article

Introduction: The COVID-19 pandemic profoundly disrupted healthcare, prompting adaptations in oncological practices. This systematic review evaluates the pandemic’s impact on the management of non-melanoma skin cancer (NMSC) of the head and neck (H&N) region. Methods: The review was reported according to PRISMA guidelines. Eligible studies compared pre-pandemic and pandemic periods in adult patients treated for head and neck NMSC reporting outcomes related to histological distribution, time to treatment initiation, reconstructive method, and surgical margin status. Risk of bias was assessed using the Newcastle–Ottawa Scale. Random-effects meta-analyses were performed for outcomes with sufficient extractable data. Results: The review comprised five studies involving 1318 cases. The relative distribution of basal cell carcinoma and squamous cell carcinoma did not differ significantly between pre-pandemic and pandemic periods. Time to treatment initiation showed no significant overall change, although heterogeneity was high, indicating substantial variability among healthcare settings. Reconstruction shifted significantly toward primary closure compared with flap reconstruction during the pandemic period (OR 1.90; 95% CI: 1.46–2.47; p < 0.0001). Negative surgical margins were reported in 1119 of 1266 excisions/cases with available data (88.4%), with no significant difference between pre-pandemic and pandemic periods (OR 0.77; 95% CI: 0.46–1.32; p = 0.34). Conclusions: The pandemic was associated with a shift toward simpler reconstructive strategies, particularly increased use of primary closure, likely reflecting attempts to reduce operative complexity and resource use. While short-term oncologic outcomes appeared broadly preserved, long-term functional, aesthetic, and patient-reported outcomes remain insufficiently characterized. Future studies should evaluate these outcomes to better inform crisis-adapted oncologic and reconstructive care pathways. 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

Objectives: Coronavirus disease 2019 (COVID-19) poses a significant threat to kidney transplant recipients (KTRs) due to chronic immunosuppression. While Azvudine has demonstrated antiviral efficacy, its long-term impact on allograft function in KTRs remains unknown. This single-arm retrospective study provides a comprehensive evaluation of the outcomes. Methods: This single-center, retrospective study consecutively enrolled 20 KTRs diagnosed with COVID-19 during the Omicron surge (December 2022–January 2023), all treated with an Azvudine-centered regimen. Clinical data, treatment responses, and serial renal function parameters were analyzed. Long-term follow-up extended to a median of 39 months. Results: The median time to COVID-19 nucleic acid negativity was 13.22 days. Renal function improved significantly during treatment: estimated glomerular filtration rate increased by a mean of 27.29 mL/min/1.73 m², and serum creatinine decreased by 57.72 µmol/L (both p < 0.01). Common complications included electrolyte imbalances and co-infections (50% of patients). Crucially, at a median follow-up of 39 months, 75% (15/20) of patients maintained normal allograft function. No Azvudine-related adverse events or drug interactions with immunosuppressants were observed. Conclusions: While acknowledging the inherent limitations of a non-comparative design, this study provides preliminary evidence suggesting that an Azvudine-centered regimen may be associated with promising efficacy, a favorable safety profile without interference with immunosuppressive therapy, and—most importantly—durable renal allograft survival in KTRs with COVID-19. Our data suggest that this regimen could contribute to mitigating the long-term risk of allograft dysfunction, potentially bringing outcomes closer to the expected baseline for stable recipients. Coupled with its low risk of drug–drug interactions, potential immunomodulatory benefits, and superior cost-effectiveness, Azvudine could be considered a valuable therapeutic option for this high-risk population in the post-pandemic era, although these findings warrant cautious interpretation. Controlled trials are ultimately needed to confirm these observations. Full article