University of Ferrara

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Human Leukocyte Antigen-G (HLA-G) is a key immunomodulatory molecule with multiple isoforms, including recently identified variants lacking the α1 domain (HLA-G Δα1). The absence of the α1 domain may reduce immune inhibition, particularly of Natural Killer (NK) cells, which are often suppressed during viral infections such as SARS-CoV-2. This suggests a novel immune regulatory mechanism that could mitigate COVID-19-related complications, including coagulopathies. This study investigates the influence of full-length and Δα1 HLA-G isoforms in NK-cell activity in vitro during SARS-CoV-2 infection and whether their expression associates with viral persistence and coagulopathy in COVID-19 patients, using vascular specimens retrieved from surgical procedures. RCC7 cell lines engineered to express either the full-length or Δα1 form of HLA-G were infected with Omicron SARS-CoV-2 to assess NK cell-mediated cytotoxicity in a co-culture system. Contrary to full-length, Δα1 HLA-G only partially inhibited NK activation, allowing greater cytotoxicity and higher IFN-I/II expression. To evaluate clinical relevance, vascular tissues from coagulopathic COVID-19 patients were analyzed for in situ SARS-CoV-2 persistence and HLA-G isoform expression. SARS-CoV-2 negative tissues more frequently expressed Δα1 and displayed higher systemic interferon (IFNs) levels. Among infection-positive cases, Δα1 expression was also associated with stronger IFN-β and IFN-γ responses. These in vivo trends mirror in vitro findings, supporting a model in which full-length HLA-G dampens NK-mediated clearance of infected vascular cells, favoring viral persistence and potentially contributing to immunothrombosis, while Δα1 permits enhanced antiviral immunity. Overall, these findings identify distinct immunomodulatory roles for HLA-G isoforms in SARS-CoV-2 infection. The Δα1 variant exhibits reduced inhibitory potency, partially preserving NK-cell antiviral functions and modulating interferon responses, whereas full-length HLA-G may facilitate vascular viral persistence and coagulopathy. HLA-G isoform profiling may thus represent a novel biomarker and therapeutic target in COVID-19 associated vascular pathology.

Abstract This chapter investigates economic discourse and argumentation across a corpus of English and Italian theoretical treatises, textbooks, and handbooks published between 1900 and 1990. We examine how epistemic and attitudinal stance markers are used to construct economic claims. By triangulating data with previous research, the analysis identifies claim-expositive lexis and concurrent markers, comparing claim presentation in theoretical treatises with that found in educational textbooks. Utilising Wmatrix7 software, we also explore key semantic domains. Results reveal consistent patterns in conveying epistemic and attitudinal stance through adverbs and complement clauses in English and Italian. Money and related subjects are identified as common semantic domains across both languages. The overarching aim is to provide a diachronic view of the evolution of argumentation in economics.

Mentalising skills may be conceptualised as composed by both personal and interpersonal competencies, in turn shaped by early adverse experiences and coping strategies. Although cross-sectional observations described a role for mentalising skills in burnout development, large-scale longitudinal studies on the topic remain limited, especially in relation to psychiatry training. The primary aim was to investigate protective and risk factors for higher burnout scores across time. Secondary aims included testing whether psychiatry exhibited different burnout scores across time in comparison to other medical residents. A cohort of 1803 medical residents (1131 psychiatry residents) was assessed for mentalising skills, conceptualised as composed of emotional regulation (Difficulties in Emotion Regulation Scale), interpersonal competencies (Interpersonal Competence Questionnaire), coping strategies (Coping Orientation to Problems Experienced) and burnout dimensions (Maslach Burnout Inventory). One-year follow-up was available for 520 psychiatry residents (73.03% response rate) and 234 other medical residents (35.94% response rate). Longitudinal mixed models and bivariate latent change models were employed. Across all residents, greater levels of burnout were associated with higher scores in insecure attachment, emotional dysregulation and maladaptive coping, as well as lower scores in interpersonal skills. Attending at least one supervision per month was associated with lower burnout scores across time. According to a bivariate latent change model, emotional regulation improvements through years were associated with lower burnout scores across time. In psychiatry residents, lower burnout scores across time were observed as compared to other medical residents. Psychiatry residents benefited from a higher protective effect of interpersonal competencies (group by moderator by time interaction) and coping strategies against burnout. Mentalising skills may mitigate burnout development. Training in psychiatry emerged as a potential mitigating factor against burnout increases. Structured supervisions may foster professional development and emotional resilience.

Atrial fibrillation (AF) is a frequent arrhythmia in sepsis patients and is traditionally regarded as a harmful epiphenomenon requiring immediate correction. Its abrupt onset and association with adverse outcomes have driven clinicians to pursue aggressive rhythm or rate control strategies, which are often extrapolated from cardiology rather than sepsis-specific evidence. However, emerging data challenge this reflexive approach. Studies with ultrashort-acting beta-blockers, such as esmolol and landiolol, have shown that hemodynamic stabilization may occur even in the absence of sinus rhythm restoration. This raises a provocative question: could AF during sepsis represent not a pathological disturbance but rather a transient and potentially tolerable manifestation of sepsis-related cardiovascular stress? We propose the concept of "permissive AF," shifting the focus from rhythm restoration to hemodynamic optimization and organ perfusion. Thus, AF is not framed as a physiological adaptation per se but as a maladaptive manifestation of sepsis-related cardiac injury that may be clinically tolerated, paralleling permissive strategies in critical care, such as permissive hypercapnia or restrictive transfusion thresholds. This does not imply therapeutic inaction; rather, it is a goal-directed approach that tolerates arrhythmia when adequate rate control and perfusion are achieved. This paradigm challenges established clinical instincts and underscores the need for individualized management. Recognizing AF as a potential adaptive rhythm reframes research priorities: identifying biomarkers of atrial inflammation, stratifying patients according to hemodynamic impact, and testing permissive versus corrective strategies in prospective trials. The permissive AF strategy proposed herein is expected to foster patient-centered care and reduce iatrogenic harm in the complex interplay between sepsis and the heart.

Background: Academic rankings may influence student enrolment, faculty recruitment, and funding opportunities, however their methodology is often criticized, primarily because it disregards financial efficiency. Methods: We analyzed the best 100 biomedical universities in three recognized international rankings (Times Higher Education, Quacquarelli-Symonds, and Shanghai), to investigate the association between expenditure and performance. Times, Q-S and SH overall quality scores, specific sub-scores, operating expenditures, and total students’ number were extracted from official websites. A global quality score was computed as weighted mean of the three scores, and a composite efficiency score was calculated dividing the average annual expenditure per student by the global quality score. Results: Despite a general alignment, the three rankings showed several discrepancies, highlighting the potential role of a composite quality score, which showed high internal validity and reliability. Sixteen of the 20 top academies were located in USA (n=12) or UK, but the median expense per student of USA universities (183,100 USD) was more than five times larger than the European, Australian (both 28,100 USD), or Canadian (25,000 USD) centers, which showed the best efficiency scores. Indeed, greater funding was significantly associated with a higher global quality score, as well as Times, SH, Q-S scores, and most sub-scores. Discussion and Conclusions: Considering the steep differences in funding that were detected between top-ranking universities and those just below the top 40, the proposed measure of efficiency may serve as a complementary metric to recognize and reward the academies that are able to maximize resources, still delivering high-quality education.

Data on the occurrence of gestational diabetes mellitus (GDM) and related offspring macrosomia are limited in women with low and delayed fertility, both of which are increasingly common in high-income countries. We evaluated the occurrence of GDM among women who delivered in Abano Terme, Italy, between January 2020 and August 2023. Baseline and clinical characteristics of women with GDM (GDM group) and those with a normal oral glucose tolerance test (control group) were analyzed in relation to neonatal macrosomia (>4000 g). Among 2600 women with low and late fertility included in the analysis, 231 (9.9%) were diagnosed with GDM. Women in the GDM group were older than control subjects (36.0 [31.5-39.0] vs. 33.0 [30.0-37.0] years; P<0.001), whereas parity did not differ between groups (2.00 [1.00-2.00] vs. 1.00 [1.00-2.00, P>0.5]). Pre-pregnancy BMI was significantly higher in the GDM group (63 [56-73] vs. 59 [54-66] kg, P<0.001), while height (164 [160-170] vs. 165 [160-170] cm, P<0.024] and gestational weight gain (GWG) (11 [8.5-14.0] vs. 13 [11.0-16.0] kg; P<0.001), P<0.001) were significantly lower. Neonatal birth weight (3400 [3080-3640] vs. 3360 [3100-3640] g; P>0.09) and the prevalence of macrosomia >4000 g (19 [8.2%] vs. 188 [8.1%]; P>0.9) did not differ between groups (P>0.09). In multivariate logistic regression analysis, the risk of GDM was significantly higher among women with low and late fertility or delayed fertility alone (odds ratios 2.3 and 1.9, respectively; P<0.001). Among maternal variables, only obesity at delivery (BMI ≥30 kg/m2) was independently associated with an increased risk of neonatal macrosomia (odds ratio 1.59; P=0.003). In women with low and late fertility, appropriate GWG may play a key role in mitigating the risk of neonatal macrosomia, even in the presence of GDM.

The immune microenvironment critically influences bone healing, particularly in the oral cavity where inflammation and microbial biofilms can compromise regeneration. Plant-derived extracellular vesicles (PDEVs) offer a biocompatible means to modulate immune responses, and apple-derived extracellular vesicles (ADEVs) have shown antioxidant and anti-inflammatory activity, although their osteoregenerative potential remains unclear. Here, we investigate the indirect effects of ADEVs on bone regeneration by assessing how their immunomodulatory action on macrophages influences the osteogenic commitment of human dental pulp stem cells (DPSCs). ADEVs were isolated, characterized, and applied to THP-1-derived macrophages to evaluate polarization via morphology and immunofluorescence for M1 (iNOS) and M2 (ARG1) markers. Then, the extracellular vesicles (EVs) from untreated and ADEV-treated macrophages were isolated and applied to DPSCs. All EVs were efficiently internalized by both macrophages and DPSCs. Treated macrophages shifted toward an M2-like phenotype, and macrophage-derived EVs (MDEVs) promoted stem cell morphological features consistent with osteogenic activation. These findings suggest that ADEVs promote osteoregeneration indirectly by influencing macrophage polarization and modifying the osteoactive cargo of MDEVs, thereby supporting their potential in cell-free, immunomodulatory approaches for oral bone regeneration.