Comprehensive profiling of anthocyanins and their derivatives in Marselan (Vitis vinifera L.) wines by UPLC-MS/MS: Influence of vintage and geographical origin.

A new estimate for global and country-level employment in agrifood systems

Disparities in interfacility transfer of patients with acute ischemic stroke have been identified at the regional level, but a national analysis has not been conducted. This study aims to evaluate patient-level trends and disparities in transfer rates based on sex, race, ethnicity, and insurance status using the Get With The Guidelines-Stroke registry. The Get With The Guidelines-Stroke registry was used to identify patients admitted with acute ischemic stroke between January 2016 and December 2021. We examined patient transfer rate by race/ethnicity groups and by patient insurance status. Odds of transferring out among each demographic group were calculated using a multivariable generalized linear mixed-effect model accounting for patient- and hospital-level confounders. Models were stratified by sex to test for any potential interaction between sex and race/ethnicity or insurance status. Among 776 556 patients transferred out of 1333 sites, Hispanic and Black patients had lower odds of being transferred compared with non-Hispanic White patients among both men and women after adjustment for stroke severity and hospital characteristics (odds ratio [OR], 0.79 [95% CI, 0.74-0.84] for Hispanic women; OR, 0.88 [95% CI, 0.83-0.93] for Hispanic men; OR, 0.80 [95% CI, 0.76-0.83] for Black women; and OR, 0.84 [95% CI, 0.81-0.88] for Black men). Differences in transfer frequency were also noted based on insurance status. In the unadjusted model and model adjusted for stroke severity, patients of all non-Medicare payment groups had higher odds of being transferred out compared with Medicare patients. However, after also adjusting for hospital characteristics, patients with Medicaid had a lower frequency of transfer compared with patients with Medicare among men and women (OR, 0.75 [95% CI, 0.71-0.78] for women with Medicaid; OR, 0.78 [95% CI, 0.75-0.82] for men with Medicaid). In this large, nationwide cohort of patients with acute ischemic stroke, Black and Hispanic patients were less likely to be transferred than non-Hispanic White patients, and patients with Medicaid were less likely to be transferred than patients with Medicare. Further work is needed to understand the contributors to this disparity and the impact on access to high-quality stroke care.

Accurate preoperative lymph node (LN) staging is critical for determining optimal surgical strategies in duodenal and pancreatic neuroendocrine neoplasms (DP-NENs). While both gallium-68-labeled somatostatin receptor (SSTR) PET/CT and contrast-enhanced CT (ceCT) offer distinct advantages for LN assessment, their comparative diagnostic accuracy remains undefined. We aimed to systematically evaluate and directly compare the diagnostic performance of 68 Ga-SSTR PET/CT and ceCT against pathologic gold standards in DP-NENs. We retrospectively analyzed 521 LNs from 136 regional stations in 42 DP-NEN patients who underwent preoperative 68 Ga-SSTR PET/CT and ceCT followed by surgical LN dissection at 2 medical centers. Pathologic validation revealed comparable detection rates for 68 Ga-SSTR PET/CT and ceCT at the patient and regional levels. However, at the individual lesion level, 68 Ga-SSTR PET/CT demonstrated significantly higher sensitivity (67.6% vs. 26.4%, P =0.008) and accuracy (96.5% vs. 94.0%). In patients with small DP-NENs (≤2cm), 68 Ga-SSTR PET/CT also exhibited superior lesion-level sensitivity (52.6% vs. 26.3%, P =0.004) and accuracy (94.0% vs. 93.5%). The size of the metastatic deposit within LNs significantly influenced 68 Ga-SSTR PET/CT detection ( P =0.036), whereas the overall LN size was associated with ceCT performance ( P =0.048). 68 Ga-SSTR PET/CT provided superior detection of lymph node metastases (LNM) compared with ceCT. Preoperative integration of 68 Ga-SSTR PET/CT, particularly in conjunction with ceCT, might enhance staging accuracy, guiding less aggressive surgical approaches and avoiding nontargeted lymphadenectomy, especially in patients with small DP-NENs.

Lipid metabolic disruption: A potential mechanistic pathway for 2,4,6-tribromophenol-induced neurotoxicity in zebrafish.

Parkinson's disease (PD) is a neurodegenerative disease characterized by preferential loss of the dopaminergic neurons in the nigrostriatal pathway. The specific molecular mechanisms for the neuronal loss remain unclear, and no cure currently exists. BDNF is a neurotrophic factor that restores the dopaminergic neurons in variant PD models. Emerging evidence suggests that simvastatin could upregulate BDNF in the brain. This study aimed to assess the neuroprotective effect of simvastatin and delineate its action mechanism. We found that simvastatin rescued the SH-SY5Y cells from MPP+ toxicity at 10 nM by upregulating BDNF and activating its downstream signaling pathways, and the protective action was significantly counteracted by BDNF siRNA or TrkB antagonist (K252a). Importantly, simvastatin upregulated BDNF via peroxisome proliferator-activated receptor alpha (PPARα) activation, as silencing the PPARα gene decreased the simvastatin-mediated BDNF upregulation and the cell viability upon exposure to MPP+. Next, we evaluated its neuroprotective effects in the PD animal model mediated by MPTP. Pretreatment with simvastatin for 2 weeks attenuated the MPTP-caused loss of the nigrostriatal dopaminergic neurons as determined by immunohistochemical staining for tyrosine hydroxylase. In parallel with the results, simvastatin ameliorated the decrease in the striatal dopamine level and behavioral impairment elicited by the neurotoxicant. Consistent with the in vitro study, simvastatin upregulated BDNF expression and restored the BDNF level in the MPTP-treated striatonigral regions. These findings suggest that simvastatin's neuroprotection may be linked to the upregulation of BDNF via activation of PPARα, and it could be a possible therapeutic intervention for the treatment of PD.

Maternal triclosan exposure impairs female offspring neurodevelopment via MeCP2 hypomethylation and enhanced MeCP2/HDAC3 interaction.

A roadmap for supporting the development of advanced therapy medicinal products in a European framework.

Policymakers increasingly aim to scale up healthcare interventions to a national scale to maximise reach and impact. However, scaling complex interventions presents challenges, particularly in balancing national standardisation with flexibility in local implementation across contexts. This study investigates how leaders experience and manage the national implementation of Proactive Health Support, a large-scale self-management support intervention in Denmark. The study employed a single-case study design with embedded units to examine the national implementation of the Proactive Health support intervention. Data were collected through 10 semi-structured interviews with leaders from the five Danish regions, over 25 hours of participant observation of leadership meetings and workshops, and a document analysis of 468 pages of leadership meeting minutes and reports. Implementing Proactive Health Support required leaders to balance the tension between fidelity and adaptation within a standardised framework. While the national framework provided stability, leaders leveraged the flexibility of implementation strategies to preserve the core intervention components while enabling local adjustments to fit diverse contexts. Reflexive practices, characterised by real-time adjustments and operating through feedback loops, both reinforcing and self-correcting, were pivotal for balancing standardisation with flexibility. Vertical leadership mediated alignment between national and regional levels, while horizontal collaboration fostered shared learning across regions. This study demonstrates the complexity of scaling healthcare interventions across diverse contexts, underscoring the non-linear and dynamic nature of such processes and the significant ongoing leadership engagement required to navigate complexity and manage uncertainty. The findings highlight collaborative leadership as crucial for enabling real-time responsiveness, fostering alignment across levels, and balancing fidelity and adaptation in national implementations. They further suggest that fidelity and adaptation are not opposing forces but complementary in practice, with adaptation in implementation strategies supporting fidelity by allowing interventions to be applied meaningfully across diverse contexts. Finally, the findings suggest that successful national implementation processes rely less on strict adherence to standardised guidelines and more on a co-adaptive process within a standardised yet flexible framework, where intervention and context are co-constructed through ongoing, leadership-driven negotiation. Part of a research programme including a registered randomised controlled trial (ClinicalTrials.gov, NCT03628469). Not applicable to this study.

Survival rates in elderly colorectal cancer patients: the impact of regional development levels

This study aims to measure the presence of spatial effects on housing sales in Türkiye at a regional level. The analysis specifically investigates the impact of interest rates, housing credit volume, and construction permits on regional housing sales in Türkiye, as well as other factors commonly used in the literature, such as real housing price, inflation, migration rate, unemployment, and GDP per capita. Using data from 2010 to 2023, NUTS-2 regions are analyzed through a spatial panel data method. The results indicate spatial interdependence in housing sales among regions of Türkiye. Furthermore, increases in the real housing price index, housing loan, interest rates, and inflation have been found to reduce housing sales, whereas increases in the total amount of housing loans and net migration rates lead to higher housing sales.

This study examines how exposure to regional inequality can be related to fairness beliefs about the poor. The hypothesis is that greater inequality is associated with a greater awareness of social disparities, resulting in a higher consensus on the necessity of helping society’s left behind. Using data from the European Social Survey across multiple regions in 25 countries, our results show a significant positive relationship between regional inequality and support for social care targeting the most disadvantaged. We find some evidence of the effect being particularly concentrated among higher income and more educated individuals. Our main findings remain robustacross multiple specifications. The research contributes to the literature by highlighting how actual inequality may shape normative beliefs about social fairness, moving beyond traditional redistribution preferences.

Chronic neuroinflammation contributes to neuronal damage through oxidative stress and inflammatory mediators, highlighting the need for novel therapeutic strategies. This study evaluated the cytotoxicity and neuroprotective effects of BD-8, a digoxin-derived cardiosteroid, in vitro and in vivo. BD-8 showed lower cytotoxicity than digoxin, with CC₅₀ values of 7.4 µM in SH-SY5Y cells and 8.5 µM in BV-2 cells, while digoxin presented a CC₅₀ of 33 nM in SH-SY5Y cells. In vivo, BD-8 did not alter cardiac, hepatic, or renal biochemical markers, supporting its systemic safety profile. In the open-field test, BD-8 prevented LPS-induced locomotor impairment, significantly increasing total crossings at 0.56mg/kg (62.07 ± 3.269; P < 0.05) and 1.12mg/kg (66.31 ± 5.282; P < 0.001) compared to the LPS group. BD-8 also reduced lipid peroxidation levels in the cortex at 0.56mg/kg (14.38 ± 0.5568; P < 0.001) and 1.12mg/kg (13.94 ± 0.8372; P < 0.001), and in the hippocampus at 1.12mg/kg (14.04 ± 0.5223; P < 0.001). Additionally, BD-8 modulated antioxidant enzyme activities, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), in both the cortex and hippocampus and reduced IL-6 levels in these brain regions without altering BDNF (Brain Derived Neurotrophic Factor) levels. These findings support BD-8 as a promising candidate for neuroinflammatory disorders.

Environmental noise is a non-specific stressor that can activate stress-response pathways and increase the production of reactive oxygen species, contributing to oxidative stress in the brain. Limbic regions such as the amygdala and hippocampus play key roles in stress processing and are particularly vulnerable to oxidative damage. Acetylsalicylic acid (ASA) has been reported to possess antioxidant and anti-inflammatory properties. Therefore, the present study aimed to determine whether ASA pretreatment provides protective effects against white noise-induced oxidative stress and inflammation, both systemically and in brain tissue. In the study, ALT (Alanine aminotransferase), creatinine, glucose, total protein, HDL (high-density lipoprotein), urea, uric acid, plasma albumin, cholesterol, and cortisol levels were measured from plasma samples. Malondialdehyde (MDA) and ascorbic acid (vitamin C) levels were measured as an antioxidant from brain tissue homogenates of the whole brain, cortex, cerebellum, amygdala, and hippocampus. interleukin 1β (IL-1β), IL-2, IL-6, granulocyte-macrophage colony-stimulating factor (GMCSF), interferon gamma ( IFN-γ), tumor necrosis factor α (TNF-α), IL-4 and IL-10 levels were measured from plasma samples. In the present study, it was found that the MDA level in the amygdala tissue was significantly lower in the animals in ASA + stress group which underwent ASA pretreatment compared to the other groups (p ≤ 0.05). There was no statistically significant difference in MDA levels in the amygdala tissues of the other three groups. A significant decrease was observed in ASA control group. MDA values in cortex tissue compared to stress control group (p ≤ 0.05). There was no significant difference between the groups regarding MDA levels of other brain regions. When whole brain tissue homogenates were examined in the ASA pretreatment groups, a significant decrease was observed in the vitamin C levels of the animals in ASA + stress group compared to the other groups. (p ≤ 0.05).There was no statistically significant change in IL-1β, IL-2, IL-6, GMCSF, IFN-γ, and IL-10 levels. It was observed that TNF-α levels increased in the groups given aspirin, and this increase was significant in ASA control group compared to stress control group (p ≤ 0.05). In the study, there was no significant change in plasma biochemical parameters ALT, creatinine, glucose, total protein, HDL, urea, and uric acid evaluations. However, plasma albumin levels were found to be higher than in control group (p ≤ 0.05). Plasma cholesterol levels were found to be decreased in stress control group compared to control group (p ≤ 0.05). When plasma cortisol levels were examined between the groups, a significant increase was observed in stress control group compared to control group (p ≤ 0.05). These findings suggest that acetylsalicylic acid may influence selected oxidative stress-related parameters in specific brain regions following white noise exposure. However, the observed effects were limited and not consistent across all biochemical and inflammatory markers examined. Further studies are needed to clarify the optimal dose and duration of ASA treatment for controlling stress-related effects.

While previous studies have suggested a declining burden of heart failure (HF) in the general population, recent evidence indicates a concerning rise in prevalence among younger individuals. However, trends in women of childbearing age (WCBA) remain understudied. This study aims to provide a comprehensive analysis of HF burden trends in WCBA at global, regional, and national levels over the past three decades, exploring the effects of age, period, and birth cohort, and projecting future trajectories to 2040. HF prevalence and years lived with disability (YLDs) in WCBA were extracted from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021. The burden was analysed globally, regionally, and nationally, with the average annual percentage change (AAPC) calculated using joinpoint regression analysis to identify significant shifts. Age-period-cohort (APC) modelling was used to assess age, period, and cohort effects, and the Bayesian age-period-cohort (BAPC) framework was applied for projections stratified by socio-demographic index (SDI). Global HF prevalence in WCBA rose from 1.51 million in 1990 to 2.68 million in 2021, with an annual growth rate of 0.49%. The disease burden was highest among women aged 40-49 years, while the fastest growth rate occurred in the 15-19 age group. Low- and low-middle SDI regions had the highest age-standardized prevalence. Significant increases were seen in East Asia (AAPC = 1.50%) and Central Sub-Saharan Africa (AAPC = 0.34%), while North America showed a decline (AAPC = -0.51%). Major causes of HF included cardiomyopathy/myocarditis, rheumatic heart disease (RHD), congenital defects, ischaemic, and hypertensive heart disease, with the latter two rising as leading causes in older age groups (≥35 years), while cardiomyopathy and RHD were more prevalent in younger WCBA. Projections for 2040 suggest a decline in middle- and high-SDI regions, while other regions are expected to see an increase. The global HF burden in WCBA has risen over the past three decades, with worsening period and cohort risks. However, high-SDI regions may see a decline in prevalence, and tailored regional prevention and treatment strategies could help mitigate the increasing burden of HF in WCBA.

Brain aging is characterized by complex alterations in both anatomical structure and neural function. While the interdependence between structural connectivity (SC) and functional connectivity (FC) is well-established, the patterns of structural-functional coupling (SFC) during aging remain largely unexplored, despite being crucial for elucidating the neural mechanisms of age-related changes. Moreover, traditional resting-state fMRI studies have predominantly focused on linear correlations, often overlooking nonlinear causal interactions that may play a pivotal role in the aging brain. To address this, we employed a Nonlinear Granger Causality (NGC) model to investigate SFC at the whole-brain level. The study included 227 healthy participants, stratified into a young group (20-35 years, [Formula: see text]) and an older group (59-77 years, [Formula: see text]), with further subgrouping by sex. We analyzed SFC from both static and dynamic perspectives at regional and subnetwork levels. Our results demonstrated that the young group exhibited significantly stronger NGC-based SFC compared to the sex-matched older group. Additionally, males displayed a higher proportion of strong SFC connections than age-matched females. Notably, a widespread age-related decline in nonlinear causal coupling was observed across both regional and subnetwork scales, particularly within networks governing cognitive control and attention. Furthermore, dynamic analyses across sliding windows confirmed the persistence of these aging patterns throughout the scanning duration, despite increased temporal variability observed in the elderly. This study underscores the importance of incorporating nonlinear causal relationships into brain network research, as this approach offers deeper insights into the potential mechanisms underlying age-related cognitive decline and neurodegenerative processes.

Civil society is crucial for societal transformation, but how its engagement can scale up and become institutionally embedded at the regional level remains widely unclear. We enhance the knowledge in this area by linking civic engagement with transformative social innovation (TSI) research. Our aim is to understand how cognitive, social, institutional, organizational and geographical proximity factors strengthen and hinder civic-led TSI initiatives by applying the proximity approach. The object of this case study was the ‘Mitmach-Region Saale-Holzland-Kreis’, an initiative which aims to establish mutual cooperation at a regional level based on solidarity and ‘commoning’. We found that engagement was based primarily on cognitive proximity, whereas organizational distance was the biggest hurdle, also suppressing positive effects from cognitive proximity. We also, most importantly, discovered that contributing to societal transformation played a role in a participant’s engagement, but was particularly suppressed by missing institutional proximity through disapproval from society or the immediate environment. Altogether, strengthening the proximities to promote engagement in civic-led TSI initiatives holds great potential for contributing to societal transformation.

Objective: This study aims to evaluate the role of the manufacturing sector in the economy of East Java by applying a base sector approach and input–output analysis. The main objective is to assess the extent to which the manufacturing sector acts as a key driver of regional economic growth and generates intersectoral linkages and multiplier effects on output, income, and employment. Design/Methods/Approach: The study adopts a quantitative approach by combining location quotient (LQ) analysis and input–output analysis. The LQ method is used to identify whether manufacturing functions as a base sector in East Java’s economy, while input–output analysis examines the sector’s forward and backward linkages with other sectors. The analytical results are further interpreted in relation to Industry 4.0 and sustainability policy frameworks in East Java. Findings: The findings indicate that the manufacturing sector has an LQ value of 1.40 (&gt;1), confirming its role as a base sector with a substantial contribution to East Java’s gross regional domestic product (GRDP). Input–output analysis reveals strong forward and backward linkages between manufacturing and other sectors. An increase in manufacturing output is shown to stimulate the growth of related sectors and generate significant multiplier effects in terms of output expansion, income generation, and employment creation. Originality/Value: This study contributes to the economic literature by integrating base-sector analysis with input–output analysis while explicitly linking multiplier effects to Industry 4.0 and sustainability policies. This combined approach offers new insights into sectoral interdependencies and illustrates how technological transformation and sustainability initiatives can enhance the competitiveness of the manufacturing sector at the regional level. Practical/Policy implication: The results highlight the importance of policies that prioritize infrastructure development, improved logistics connectivity, and human capital development through vocational education and training aligned with Industry 4.0 technologies. In addition, incentives for green industries, export promotion, and strengthened international cooperation are essential to expand markets and enhance competitiveness. These policy recommendations can be applied to reinforce the manufacturing sector as a strategic pillar for sustainable economic growth in East Java.

Creating antibiograms solely for adults may overestimate resistance of antimicrobials for certain pathogens in children. The Canadian Paediatric Society comments that areas with no cephalosporin-resistant Streptococcus pneumoniae cases should consider ceftriaxone or cefotaxime monotherapy for meningitis, despite most experts recommending adding vancomycin. The present study created age-specific antibiograms using LifeLabs data to report incidences of resistant bacterial meningitis pathogens at the regional level to determine the need for duo-coverage. Data of common bacterial meningitis pathogen susceptibility was collected from 1 January 2023 to 31 December 2024, in the LifeLabs community laboratory on Vancouver Island. Most Streptococcus pneumoniae isolates (78/83) were susceptible to ceftriaxone using the meningitis breakpoint; the remaining five isolates showed intermediate susceptibility to ceftriaxone. There was a significant difference when comparing S. pneumoniae susceptibility using penicillin-meningitis and penicillin-non-meningitis breakpoints (82% vs. 99%, respectively; p < 0.05). There was a significant difference between the three age groups (<18 years, 18-50 years, >50 years) when analyzing ciprofloxacin susceptibility of isolates [82% (n = 462), 77% (n = 2452), 75% (n = 8352), respectively, p < 0.05]. Ceftriaxone should remain the drug of choice for community-acquired bacterial meningitis and might be sufficient as a monotherapy for pneumococcal meningitis on Vancouver Island. The age-specific differences in E. coli susceptibilities to ciprofloxacin showed the importance of age-specific antibiograms.

Language network reorganization in temporal lobe epilepsy: insights from task-based functional MRI.