Search Results (81)

Background: Increasing evidence suggests that schizophrenia may be associated with peripheral immune–inflammatory alterations, although the distributional characteristics and heterogeneity of routinely available complete blood count (CBC)-derived inflammatory indices in real-world psychiatric inpatient settings remain insufficiently characterized. The present study aimed to descriptively evaluate the distributional properties of CBC-derived inflammatory markers in hospitalized patients with schizophrenia using an exploratory panel-based analytical framework. Methods: We conducted a retrospective cross-sectional analysis using anonymized CBC laboratory panels obtained from hospitalized patients with schizophrenia at a tertiary psychiatric center. Following panel reconstruction and quality control procedures, 858 structurally valid CBC panels were included in the analyses. Primary inflammatory indices included neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune–inflammation index (SII). Descriptive distributional analyses, threshold-based prevalence estimation, Spearman correlation analyses, and exploratory unsupervised clustering procedures were performed to evaluate inflammatory variability and internal distributional patterns within the dataset. Results: Median NLR was 2.51 (IQR: 1.95–3.55), median MLR was 0.25 (IQR: 0.19–0.31), median PLR was 124.10 (IQR: 100.40–163.94), and median SII was 686.96 (IQR: 484.81–1045.85). Threshold-based analyses demonstrated substantial variability in inflammatory burden distributions, with 35.9% of panels showing NLR > 3 and 27.0% demonstrating SII > 1000. Correlation analyses revealed strong positive associations among NLR, PLR, and SII, whereas RDW-CV and MPV demonstrated weaker and more heterogeneous relationships with the principal inflammatory indices. Exploratory clustering analyses generated two distributional clusters, including a smaller cluster exhibiting relatively higher NLR, MLR, PLR, SII, WBC, and platelet values than the remaining panels. Female panels demonstrated significantly higher PLR and SII distributions following false discovery rate (FDR) correction. Conclusions: The present findings suggest that CBC-derived inflammatory indices demonstrate substantial distributional variability within this panel-based schizophrenia dataset. Although the exploratory design, absence of patient-level linkage, and lack of clinical confounder adjustment substantially limit biological interpretation, routinely available hematological inflammatory markers may still provide a pragmatic framework for descriptive characterization of inflammatory variability patterns in real-world psychiatric populations. Future patient-level longitudinal studies integrating clinical, pharmacological, and molecular variables will be necessary to determine the potential clinical relevance of inflammatory heterogeneity in schizophrenia. Full article

Backgrounds: Carotid atherosclerotic plaques (CAPs) are a reliable marker of systemic atherosclerosis and a predictor of cardiovascular events. Despite advances in prevention, the prevalence of CAPs in high-income regions remains uncertain due to heterogeneity in imaging definitions, study designs, and populations. We strived to provide an updated meta-analysis of population-based studies conducted in Europe and North America between 2015 and 2025, estimating the prevalence of CAPs in general populations. Methods: Following the PRISMA 2020 guidelines, PubMed and Web of Science were searched for original studies. Eligible studies reported CAPs prevalence in adult general populations using ultrasonography, computed tomography angiography, and magnetic resonance imaging. Pooled prevalence was calculated using a random-effects meta-analysis of proportions, and heterogeneity was assessed using I² and τ² statistics. Subgroup and meta-regression analyses explored associations with age and comorbidities. Results: A total of 80 studies comprising 177,196 participants were included. The pooled prevalence of CAPs was 39.8% (95% CI 32.6–47.5%) under a random-effects model with substantial heterogeneity (I² = 99.6%). The prevalence of CAPs increased with age, exceeding 59% among individuals aged over 70 years. High-risk populations, particularly those with T2DM, exhibited a prevalence exceeding 50%. Conclusions: CAPs are present in approximately 40% of adults in Europe and North America, with prevalence strongly driven by age and comorbidities. Despite therapeutic advances, the prevalence of CAPs has not declined, reflecting the growing impact of population aging and comorbidities. Standardized imaging definitions, longitudinal outcome linkage, and pragmatic prevention strategies are needed to translate CAPs detection into reduced cardiovascular events. Full article

Acute respiratory failure (ARF) often leads to ICU admission, ventilatory support, illness, and death. The usual classification into hypoxemic and hypercapnic types does not capture its full complexity. Precision medicine uses the concept of “treatable traits” to guide care based on traits that are clinically relevant, identifiable, measurable, and possibly changeable. Arterial carbon dioxide pressure (PaCO₂) reflects factors like alveolar ventilation, dead space, respiratory mechanics, and how patients respond to ventilatory support. This makes it clinically relevant in selected situations. We carried out a scoping review using PRISMA-ScR and JBI guidelines to summarize evidence on hypocapnia and hypercapnia as prognostic, stratification, or clinically relevant variables during respiratory support. We searched PubMed/MEDLINE, ScienceDirect, and Web of Science (1994–2025), and checked references by hand. Thirty-four studies met our criteria and were grouped into four areas: pre-intubation or early acute presentation, non-invasive support (NIV/HFNC), invasive mechanical ventilation (IMV), and weaning or post-extubation. In summary, hypocapnia was linked to worse outcomes or failure of support in hypoxemic or cardiogenic cases. Hypercapnia helped identify patients who benefited from NIV, such as those with chronic obstructive pulmonary disease or obesity hypoventilation. For IMV, the effects depended on the presence and severity of acidosis and on its duration. Overall, PaCO₂ showed context-dependent clinical relevance, acting mainly as a prognostic or stratification marker and, in narrower settings, as a variable that may inform monitoring or support decisions. This review provides a pragmatic framework for interpreting PaCO₂ across respiratory support contexts and highlights the need for safe and clinically meaningful targets. Full article

This paper aims to offer a state-of-the-art overview of the ways in which research on Modern Greek has informed—and been informed by—theorizing in the field of pragmatics. In charting this (rather uncharted) territory, our aim is to demonstrate that Modern Greek pragmatics does not only reflect the evolution of pragmatic enquiry from a narrow conceptualization to a much broader one that encompasses interactional, social and cultural specifications, but has also contributed new insights into pragmatic theory that surpass the purview of Modern Greek linguistics. While acknowledging that delimiting the remit of pragmatics is far from evident or even unanimously agreed, our overview envisages to provide the reader with a roadmap of past and ongoing research with a view to highlighting how general pragmatic principles interact with the language- and culture-specific parameters that are available to speakers of Modern Greek. Full article

This study examines the historical and functional divergence between two Spanish general extenders, y todo eso and y todo, in order to determine whether the loss of syntactic analyzability can serve as a criterion for distinguishing stages of grammaticalization and identifying pragmatic shifts. Drawing on extensive diachronic and synchronic corpus data, the analysis compares the formal evolution, semantic properties and pragmatic functions of both constructions. The results show that y todo eso follows a prototypical grammaticalization path marked by a progressive reduction in its internal structure, the weakening of referential meaning, and increasing freedom from syntactic constraints, while preserving analyzability through alternation with the simpler form y eso. In contrast, y todo displays an earlier and more advanced process of grammaticalization, dating back to medieval Spanish, in which the construction undergoes semantic bleaching, loss of additive value, and reanalysis as a scalar focus marker. These findings support the view that y todo no longer functions as a general extender in contemporary Spanish, whereas y todo eso retains this status, illustrating how syntactic analyzability correlates with shifts between pragmatic categories. Full article

Background: The gut microbiome contributes to immune–metabolic homeostasis through microbial-derived metabolites such as short-chain fatty acids (SCFAs). However, whether early disruption of the gut microbiome–SCFA axis identifies impaired clinical recovery in pediatric intensive care unit (PICU) patients remains unclear. Biological markers reflecting the recovery trajectory beyond conventional severity scores remain poorly characterized in pediatric critical illness. We therefore investigated whether early microbiome disruption and fecal SCFA profiles are associated with recovery trajectory in critically ill children. Methods: In this prospective observational study (N = 26), fecal samples were collected within 5 days of PICU admission. Microbial diversity was assessed using 16S rRNA gene sequencing (Shannon index), and fecal SCFAs were quantified using targeted metabolomics. Disease severity was assessed using the Pediatric Index of Mortality 3 (PIM3). The primary outcome was PICU length of stay (LOS) as a pragmatic indicator of metabolic and functional recovery trajectory in critically ill children. Results: Younger age and higher disease severity showed a trend toward reduced microbial diversity (β = 0.066, p = 0.089, and β = −0.054, p = 0.089). Early loss of gut microbial diversity was associated with reduced fecal butyric acid concentrations (r = 0.440, p = 0.024). Importantly, lower microbial diversity in the early sampling window showed a significant inverse correlation with PICU LOS (ρ = −0.428, p = 0.029), whereas fecal butyric acid alone was not directly associated with LOS (p = 0.321). In multivariable regression models adjusting for age, disease severity, and clinical exposures, microbial diversity showed a consistent inverse association with PICU LOS, although statistical significance was not reached. Conclusions: Early disruption of the gut microbiome–SCFA axis, characterized by reduced microbial diversity and lower fecal butyrate, showed trend-level associations with delayed clinical recovery in this pilot cohort. Gut microbial ecosystem integrity may serve as a biologically relevant marker of recovery trajectory beyond conventional severity scoring. Full article

Background: An individual’s health status is determined by the interaction of genetic, environmental, social, and lifestyle variables. Nutrition plays a fundamental role in disease prevention, a notion widespread among the informed public, which is keen on participating in initiatives for personalized recommendations informed by advanced biological data. Objectives: To evaluate whether a personalized nutrition service can produce measurable changes in nutritional behavior and biological outcomes, we established the GENIE digital platform. This platform delivers personalized online food shopping and recipe recommendation informed by integrated data from (i) biochemical blood markers, (ii) nutrigenetic profiles, (iii) gut microbiota composition, and (iv) consumer preferences. Methods: We conducted a single-arm study in a Spanish cohort that used a specific online retailer for food shopping, totaling 1177 participants. Group 1 (n = 620) had recommendations based only on the biochemical blood test; Group 2 (n = 357) included the nutrigenetic test; and Group 3 had the gut microbiome test (first batch, n = 200; second batch, n = 97). After one month of informed, tailored dietary advice, a quantitative evaluation of the experience was conducted. Results: The GENIE platform led to strong engagement (mean session time 7.07 min; +154% e-commerce use), with 71% of participants following at least part of the recommendations. This was associated with an increase in microbiome diversity in about 70% of participants, after just one month of guided recommendations. Conclusions: The GENIE platform represents a pragmatic model for translating nutrigenetic and microbiome data into actionable dietary recommendations, bridging the gap between scientific evidence and consumer behavior. Full article

Elderly psoriasis patients (≥65 years) demonstrate mainly preserved but substantially delayed therapeutic responses to IL-17 and IL-23 inhibitors, achieving lower PASI90 rates at early time-points with eventual “catch-up” by week 52, alongside increased adverse-event-driven discontinuation. This review synthesizes clinical efficacy data from real-world studies with emerging mechanistic evidence on immunosenescence and cellular senescence to propose the “Inflammatory Noise Floor” hypothesis. We postulate that senescent keratinocytes and fibroblasts constitutively secrete SASP cytokines (IL-6, IL-8, TNF-α) through pathways partially independent of IL-23/IL-17, potentially establishing a persistent baseline inflammation that IL-23/IL-17 blockade might not suppress. Concurrently, immunosenescence, characterized by CD8⁺CD28⁻ T-cell accumulation, exhaustion marker upregulation, and Treg dysfunction, is hypothesized to impair adaptive immune re-equilibration. This dual mechanism represents one plausible, albeit theoretical, explanatory framework for the temporal lag, PASI plateau effects, and infection risk observed in elderly patients. Optimizing outcomes in the elderly may require a pragmatic approach: accepting stable PASI 75-90 as a successful endpoint and prospectively validating extended assessment timelines. While a direct correlation remains to be proven, this framework identifies cellular and immunosenescence as potential targets for future senotherapeutic interventions. Full article

Background: Pembrolizumab combined with pemetrexed–platinum chemotherapy is the standard first-line treatment for patients with metastatic non-squamous non-small-cell lung cancer (NSCLC) and a PD-L1 tumor proportion score (TPS) of 1–49%. Real-world data on treatment outcomes and the prognostic relevance of immune-related adverse events (irAEs) in this population remain limited, particularly in Eastern Europe. Methods: We conducted a retrospective, single-center real-world study including patients with metastatic non-squamous NSCLC and PD-L1 TPS of 1–49% treated with first-line pembrolizumab plus pemetrexed–platinum chemotherapy between June 2024 and May 2025. Progression-free survival (PFS) was estimated using the Kaplan–Meier method. Cox proportional hazards models were used to evaluate factors associated with PFS, including baseline clinical characteristics and organ-specific irAEs graded according to CTCAE v5.0. Results: A total of 107 patients were included. Median PFS for the entire cohort was 7.03 months (95% CI, 4.81–9.26). Immune-related adverse events occurred in 52 patients (48.6%), with thyroid (21.5%) and skin (13.1%) irAEs being the most frequent. The majority of irAEs were grade 1–2, while grade 3–4 events were rare (4.7%) and limited to hepatic toxicity and pneumonitis, all leading to treatment discontinuation. In multivariate analysis, ECOG performance status 2 was independently associated with inferior PFS (HR 3.09, 95% CI 1.74–5.48; p < 0.001). Conversely, the occurrence of thyroid irAEs (HR 0.36, 95% CI 0.17–0.78; p = 0.009) and skin irAEs (HR 0.28, 95% CI 0.10–0.79; p = 0.016) was independently associated with prolonged PFS, whereas pulmonary, hepatic, and gastrointestinal irAEs were not. Conclusions: In this real-world cohort of patients with metastatic non-squamous NSCLC treated with first-line pembrolizumab–chemotherapy, clinical outcomes were consistent with prior real-world experience. These findings suggest that low-grade, manageable immune toxicities may serve as pragmatic on-treatment markers of benefit. However, given the retrospective design, limited sample size, and the absence of time-dependent analyses, these associations should be interpreted with caution and considered hypothesis-generating rather than causal. Full article

Background and Objectives: Ascites is associated with substantial symptom burden and increased healthcare utilization, and it is observed in patients with advanced disease across multiple etiologies. However, because ascites is a clinical sign rather than a diagnosis category, it can be challenging to study using routine health reporting. In routinely collected hospital administrative data, ascites is commonly captured using International Classification of Diseases, Tenth Revision (ICD-10) code R18, an etiologically non-specific classification whose outcome implications are less documented. We aimed to evaluate the incremental association of R18-coded ascites with length of stay (LOS), readmission burden, and in-hospital mortality in the Gastroenterology and Internal Medicine inpatient department, beyond comorbidity burden and other coded decompensation proxies. Materials and Methods: We conducted a single-center retrospective study using routinely collected administrative discharge data from adult inpatient admissions (2015–2023) in the Gastroenterology and Internal Medicine department of a Romanian tertiary-care hospital. Admissions were classified by the presence of ICD-10 R18-coded ascites. Outcomes were LOS, readmission burden (count of subsequent admissions), and in-hospital mortality. Multivariable models adjusted for age, sex, and comorbidity burden (Charlson Comorbidity Index), with additional models incorporating ICD-10-derived decompensation proxies to assess overlap in administrative severity signal. LOS was further examined within Charlson strata to evaluate incremental stratification. Results: Coded ascites was associated with higher hospital burden, including longer LOS and greater readmission burden, and with higher in-hospital mortality in partially adjusted models. Within each CCI stratum, LOS remained higher among admissions with R18-coded ascites, supporting incremental stratification beyond comorbidity alone. Furthermore, mobility impairment was an important predictor of LOS. Age-stratified analyses suggested a high-burden phenotype among younger patients and infrequent R18 coding among the very elderly in this cohort. Conclusions: These findings support the potential utility of R18-coded ascites as a pragmatic administrative marker for risk adjustment and service planning. Full article

Background/Objectives: In Puerto Rico (PR), lung cancer mortality remains high because diagnoses frequently occur at advanced stages. Although low-dose computed tomography (LDCT) lowers lung cancer–specific mortality, this screening is difficult to operationalize locally due to high false-positive rates, radiology capacity constraints, payer limitations, and geographic barriers affecting rural populations. Methods: We performed a narrative review on the literature from 2001–2026 of established and emerging detection strategies—LDCT; serum biomarkers (CEA, CYFRA-21-1, NSE, ProGRP, SCC-Ag, HE4, Hp, TAAb); breath analysis (FeNO and VOCs); and liquid biopsy (ctDNAs/CTCs/miRNAs). We assessed technical performance, feasibility, and health-system fit in PR and then synthesized these findings into an implementable biomarker-first triage workflow for are. Results: Multiplex serum panels analyzed with machine learning outperform single markers and TAAb provide high specificity with biological lead time, supporting their use as a triage gateway before LDCT. Breathomics is also feasible at the point of care. Liquid biopsy has modest sensitivity in very-early disease yet provides molecular adjudication for indeterminate nodules. A stepwise pathway—expanded risk assessment, integrated multi-panel testing in primary care, LDCT reserved for biomarker-positive individuals, and liquid biopsy when imaging is inconclusive—can enrich pre-test probability, reduce unnecessary scans, align with capitation, and protect limited radiology capacity. Conclusions: An integrated, non-invasive, biomarker-first triage model offers a pragmatic, equitable route to earlier lung cancer detection in PR and resource stewardship, while reducing disparities. Full article

Background/Objectives: In real-world gastric cancer cohorts, incomplete TNM staging and heterogeneous biomarker testing may result from structural characteristics of diagnostic pathways rather than random data loss. This study aimed to evaluate staging completeness and tumour marker availability as pathway-linked phenomena and to examine their associations with metastatic presentation and treatment allocation at diagnosis. Methods: This retrospective observational study included consecutive patients with histologically confirmed gastric carcinoma or adenocarcinoma diagnosed between 2018 and 2021 at a tertiary referral centre. Incomplete staging was defined a priori as the presence of Tx and/or Nx and/or Mx. The primary analytic endpoint was incomplete staging within the subset of patients with defined M status. Secondary analyses evaluated the availability of both CEA and CA19-9. Univariable associations were assessed using Pearson’s χ², and multivariable logistic regression models estimated adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Predefined pathway-oriented endpoints were analysed using multivariable logistic regression models adjusted for key clinical and diagnostic variables. Results: Among 375 patients, incomplete staging occurred frequently and was strongly associated with metastatic disease (M1) and non-surgical management. In multivariable analysis, metastatic presentation remained independently associated with incomplete staging, whereas surgical management and explicit documentation of disease extension were inversely associated. Concurrent availability of CEA and CA19-9 was concentrated within non-surgical and metastatic pathways and was independently associated with documented disease extension. These findings suggest that both staging completeness and tumour marker testing are determined by pathway-specific structures rather than random processes. Conclusions: In real-world gastric cancer care, incomplete TNM staging and tumour marker availability function as measurable features of diagnostic architecture rather than random data limitations. By modelling documentation completeness and testing availability as pathway-dependent phenomena, this study provides a pragmatic framework for improving transparency and interpretability in observational oncology research. Full article

Background and Objectives: Bone fragility in people living with HIV (PLWH) reflects both reduced bone mineral density (BMD) and impaired microarchitecture, while functional decline may further amplify fracture vulnerability. This study evaluated whether adding a pragmatic sarcopenia screen improves bone fragility characterization beyond DXA-BMD, trabecular bone score (TBS), calcaneal quantitative ultrasound (QUS), and biomarkers, and explored the relationship between tenofovir disoproxil fumarate (TDF) exposure and microarchitectural impairment. Materials and Methods: In this single-center cross-sectional study at Victor Babeș University of Medicine and Pharmacy Timișoara, 98 adults on stable ART underwent DXA (T-scores), lumbar TBS (reported as TBS × 100), calcaneal QUS (SOS/BUA), and bone turnover markers (CTX, P1NP, 25(OH)D). Sarcopenia screening used handgrip strength and 4 m gait speed. Associations were tested using group comparisons, correlations, and multivariable modeling for degraded TBS (TBS × 100 < 124.0). Results: Sarcopenia screen-positive participants (n = 28) had lower TBS (123.8 vs. 127.7, p = 0.02), lower lumbar T-score (−1.7 vs. −1.2, p = 0.014), lower SOS (1523.3 vs. 1548.8 m/s, p = 0.002), and higher CTX (0.6 vs. 0.4 ng/mL, p < 0.001), with less frequent viral suppression (60.7% vs. 85.7%, p = 0.006). With >5 years TDF exposure (n = 28), degraded TBS prevalence was 82.1% vs. 40.0% in never-exposed (p = 0.001), alongside lower TBS (123.1 vs. 129.8, p < 0.001) and higher CTX (0.6 vs. 0.4 ng/mL, p < 0.001). Viral suppression independently reduced odds of degraded TBS (aOR 0.3, 95% CI 0.1–0.9; p = 0.034). Conclusions: In PLWH, prolonged TDF exposure and functional impairment co-occur with worse densitometric and microarchitectural profiles; viral suppression shows an independent protective association with microarchitecture. Full article

The Carpathian Basin is a coherent biogeographic unit whose wildlife populations and pathogen dynamics are increasingly reshaped by administratively fragmented governance, land-use change and linear infrastructure. This review synthesizes evidence that the permeability patterns governing host movement also structure the transboundary exchange of genes and infections, creating a connectivity substrate for conservation genetics and One Health risk. Focusing on wild boar (Sus scrofa), red deer (Cervus elaphus), roe deer (Capreolus capreolus), fallow deer (Dama dama) and the expanding golden jackal (Canis aureus), we integrate population genetic inferences with wildlife epidemiology to examine how highways, border fences and asymmetric management (e.g., supplemental, feeding practices, hunting pressure and surveillance regimes) can generate biological asymmetries across boundaries. We highlight African swine fever as an emblematic disturbance in wild boar populations, discuss cervid risks including tick-borne pathogens and chronic wasting disease (CWD) preparedness and evaluate zoonotic threats associated with carnivore expansion (e.g., Echinococcus spp.). We propose a Carpathian Basin-level monitoring and data-sharing architecture, coupling harmonized passive surveillance, strategic active surveillance for priority pathogens, and standardized genetic marker panels supported by interoperable metadata. A Basin-scale One Health approach is a pragmatic prerequisite for the coordinated prevention, early detection and resilient management of cross-border epizootics and zoonotic threats. Full article

In (colloquial) Italian, the fixed expression mi sa functions as an evidential/epistemic marker, requiring the dative 1SG clitic experiencer and the 3SG default form of the verb sapere. Mi sa diachronically develops from the verb for taste/smell, sapere, which is still productive in contemporary Italian, and the structure that it projects. This comprises an obligatory PP introduced by di encoding the type/quality of taste/smell (often metaphorically extended); a subject expressing the perceived entity; and an optional dative experiencer. We systematically analyzed data from the KIParla corpus, comparing the distribution of mi sa to the distribution of one of the most frequent Italian epistemic verb forms, namely, credo ‘I believe’. This study aimed to establish how the original perceptual meaning of mi sa influences its epistemic meaning. The results suggest that the persistence of the original object-oriented perception verb makes mi sa more likely to appear in particular contexts, i.e., events/situations that are known by the speaker through an inferential-like process. Furthermore, mi sa can only rarely be uttered out of the blue and seems to need a situative context (a stage), often containing an explicit QUD. Full article