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Despite global commitments to universal health coverage, persons with disabilities (PwD) continue to face significant barriers in accessing appropriate healthcare, including diagnostics, treatments and preventive healthcare, with lower participation in cancer screening and vaccination programs. These disparities are driven by diverse, intersecting obstacles (structural, financial, communicative, and social) that vary by disability type and context. Inclusive approaches, co-designed with PwD and supported by standardized assessment tools, are urgently needed to address persistent inequities in healthcare access and outcomes.

Long pentraxin 3 (PTX3) is an essential component of humoral innate immunity, involved in resistance to selected pathogens and in the regulation of inflammation 1 – 3 . The present study was designed to assess the presence and significance of PTX3 in Coronavirus Disease 2019 (COVID-19) 4 – 7 . RNA-sequencing analysis of peripheral blood mononuclear cells, single-cell bioinformatics analysis and immunohistochemistry of lung autopsy samples revealed that myelomonocytic cells and endothelial cells express high levels of PTX3 in patients with COVID-19. Increased plasma concentrations of PTX3 were detected in 96 patients with COVID-19. PTX3 emerged as a strong independent predictor of 28-d mortality in multivariable analysis, better than conventional markers of inflammation, in hospitalized patients with COVID-19. The prognostic significance of PTX3 abundance for mortality was confirmed in a second independent cohort (54 patients). Thus, circulating and lung myelomonocytic cells and endothelial cells are a major source of PTX3, and PTX3 plasma concentration can serve as an independent strong prognostic indicator of short-term mortality in COVID-19. Mantovani and colleagues report elevated circulating concentrations of the long pentraxin PTX3 in patients with severe COVID-19. Within this cohort, early detection of high PTX3 concentrations emerged as a strong predictor of decreased survival.

The presence of NaCl in soil or water is one of the most critical environmental stresses limiting crop productivity worldwide. Seaweed extract (SWE) represents an important category of plant biostimulants able to improve crop tolerance to abiotic stresses, such as salinity. The current research aimed at elucidating the physiological and anatomical effects as well as the changes in mineral composition of greenhouse zucchini squash ( Cucurbita pepo L.) treated with Ecklonia maxima SWE. Plants were sprayed every 2 weeks with a solution containing 3 mL L −1 of SWE. Zucchini squash plants were supplied with four nutrient solutions: 1 (non-salt control), 20, 40, or 60 mM NaCl. Increased salinity in the nutrient solution triggered a decrease in marketable yield, shoot biomass, Soil Plant Analysis Development (SPAD) index, net CO 2 assimilation rate ( A CO2 ), transpiration rate ( E ), and leaf macronutrient concentration (P, K, Ca, and Mg), whereas it augmented Na and Cl concentrations in leaf tissue without altering PSII photochemistry. Anatomical changes in leaves, including an increase in lamina, palisade, spongy parenchyma thickness, and intercellular spaces, were recorded under saline conditions. Foliar application of SWE increased yield and shoot biomass by 12.0 and 17.4 %, respectively, as well as fruit dry matter and total soluble solid contents in comparison to untreated plants. This was associated with an improvement in A CO2 (+14 %), chlorophyll content (+8 %), and nutritional status (high K and low Na accumulation) in SWE-treated plants. The size of stomata was influenced by foliar application of SWE, since the smallest cell guard length and width were recorded in the leaves of SWE-treated plants. Finally, the phenolic compounds in both palisade and spongy parenchyma were higher in untreated than in SWE-treated plants.

Enteric glial cells (EGCs), the major components of the enteric nervous system (ENS), are implicated in the maintenance of gut homeostasis, thereby leading to severe pathological conditions when impaired. However, due to technical difficulties associated with EGCs isolation and cell culture maintenance that results in a lack of valuable in vitro models, their roles in physiological and pathological contexts have been poorly investigated so far. To this aim, we developed for the first time, a human immortalized EGC line (referred as ClK clone) through a validated lentiviral transgene protocol. As a result, ClK phenotypic glial features were confirmed by morphological and molecular evaluations, also providing the consensus karyotype and finely mapping the chromosomal rearrangements as well as HLA-related genotypes. Lastly, we investigated the ATP- and acetylcholine, serotonin and glutamate neurotransmitters mediated intracellular Ca 2+ signaling activation and the response of EGCs markers ( GFAP , SOX10 , S100β , PLP1 , and CCL2 ) upon inflammatory stimuli, further confirming the glial nature of the analyzed cells. Overall, this contribution provided a novel potential in vitro tool to finely characterize the EGCs behavior under physiological and pathological conditions in humans.

Purpose: Build predictive radiomic models for early relapse and BRCA mutation based on a multicentric database of high-grade serous ovarian cancer (HGSOC) and validate them in a test set coming from different institutions. Methods: Preoperative CTs of patients with HGSOC treated at four referral centers were retrospectively acquired and manually segmented. Hand-crafted features and deep radiomics features were extracted respectively by dedicated software (MODDICOM) and a dedicated convolutional neural network (CNN). Features were selected with and without prior harmonization (ComBat harmonization), and models were built using different machine learning algorithms, including clinical variables. Results: We included 218 patients. Radiomic models showed low performance in predicting both BRCA mutation (AUC in test set between 0.46 and 0.59) and 1-year relapse (AUC in test set between 0.46 and 0.56); deep learning models demonstrated similar results (AUC in the test of 0.48 for BRCA and 0.50 for relapse). The inclusion of clinical variables improved the performance of the radiomic models to predict BRCA mutation (AUC in the test set of 0.74). Conclusions: In our multicentric dataset, representative of a real-life clinical scenario, we could not find a good radiomic predicting model for PFS and BRCA mutational status, with both traditional radiomics and deep learning, but the combination of clinical and radiomic models improved model performance for the prediction of BRCA mutation. These findings highlight the need for standardization through the whole radiomic pipelines and robust multicentric external validations of results.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with elevated prevalence of comorbidities, especially metabolic and cardiovascular diseases. We used a tool called Heart Rate Variability (HRV) in order to assess the correlation between HS and alterations of the sympathetic-vagal equilibrium in the autonomic cardiovascular regulation system. We found increased sympathetic activity, associated with a higher risk of cardiovascular disease. HS, according to our results, is an independent cardiovascular risk factor.

Infections by carbapenem-resistant Klebsiella pneumoniae (CRKp) represent a challenging problem after SCT. A retrospective survey (January 2010 to July 2013) involving 52 Italian centers was performed to assess the epidemiology and the prognostic factors of CRKp infections in auto- and allo-SCT. Cases of CRKp infection were reported in 53.4% of centers. CRKp infections were documented in 25 auto-SCTs and 87 allo-SCTs, with an incidence of 0.4% (from 0.1% in 2010 to 0.7% in 2013) and 2% (from 0.4% in 2010 to 2.9% in 2013), respectively. A CRKp colonization documented before or after transplant was followed by an infection in 25.8% of auto-SCT and 39.2% of allo-SCT patients. The infection-related mortality rates were 16% and 64.4%, respectively. A pre-transplant CRKp infection (hazard ratio (HR) 0.33, 95% confidence intervals (CIs) 0.15–0.74; P =0.007) and a not CRKp-targeted first-line treatment (HR 2.67, 95% CI 1.43–4.99; P =0.002) were independent factors associated with an increased mortality in allo-SCT patients who developed a CRKp infection. Our study shows challenging findings of CRKp infections in SCT patients in Italy particularly after allo-SCT. The detection of carriers and the definition of early therapeutic strategies represent critical aspects of the management of CRKp infections after SCT.

The fibroblast growth factors (FGFs) are key regulators of embryonic development, tissue homeostasis and tumour angiogenesis. Binding of FGFs to their receptor(s) results in activation of several intracellular signalling cascades including phosphoinositide 3-kinase (PI3K) and phospholipase C (PLC)gamma1. Here we investigated the basic FGF (FGF-2)-mediated activation of these enzymes in human umbilical vein endothelial cells (HUVECs) and defined their role in FGF-2-dependent cellular functions. We show that FGF-2 activates PLCgamma1 in HUVECs measured by analysis of total inositol phosphates production upon metabolic labelling of cells and intracellular calcium increase. We further demonstrate that FGF-2 activates PI3K, assessed by analysing accumulation of its lipid product phosphatidylinositol-3,4,5-P(3) using TLC and confocal microscopy analysis. PI3K activity is required for FGF-2-induced PLCgamma1 activation and the PI3K/PLCgamma1 pathway is involved in FGF-2-dependent cell migration, determined using Transwell assay, and in FGF-2-induced capillary tube formation (tubulogenesis assays in vitro). Finally we show that PI3K-dependent PLCgamma1 activation regulates FGF-2-mediated phosphorylation of Akt at its residue Ser473, determined by Western blotting analysis. This occurs through protein kinase C (PKC)alpha activation since dowregulation of PKCalpha expression using specific siRNA or blockade of its activity using chemical inhibition affects the FGF-2-dependent Ser473 Akt phosphorylation. Furthermore inhibition of PKCalpha blocks FGF-2-dependent cell migration. These data elucidate the role of PLCgamma1 in FGF-2 signalling in HUVECs demonstrating its key role in FGF-2-dependent tubulogenesis. Furthermore these data unveil a novel role for PLCgamma1 as a mediator of PI3K-dependent Akt activation and as a novel key regulator of different Akt-dependent processes.

Background: The melanocortin-1-receptor ( MC1R ) gene regulates human pigmentation and is highly polymorphic in populations of European origins. The aims of this study were to evaluate the association between MC1R variants and the risk of non-melanoma skin cancer (NMSC), and to investigate whether risk estimates differed by phenotypic characteristics. Methods: Data on 3527 NMSC cases and 9391 controls were gathered through the M-SKIP Project, an international pooled-analysis on MC1R , skin cancer and phenotypic characteristics. We calculated summary odds ratios (SOR) with random-effect models, and performed stratified analyses. Results: Subjects carrying at least one MC1R variant had an increased risk of NMSC overall, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC): SOR (95%CI) were 1.48 (1.24–1.76), 1.39 (1.15–1.69) and 1.61 (1.35–1.91), respectively. All of the investigated variants showed positive associations with NMSC, with consistent significant results obtained for V60L, D84E, V92M, R151C, R160W, R163Q and D294H: SOR (95%CI) ranged from 1.42 (1.19–1.70) for V60L to 2.66 (1.06–6.65) for D84E variant. In stratified analysis, there was no consistent pattern of association between MC1R and NMSC by skin type, but we consistently observed higher SORs for subjects without red hair. Conclusions: Our pooled-analysis highlighted a role of MC1R variants in NMSC development and suggested an effect modification by red hair colour phenotype.

Abstract Background In 2018, Lombardy's Fight Against Sepsis in Obstetrics group developed a regional sepsis management bundle for obstetric patients. This study aimed to evaluate the impact of this bundle on maternal and neonatal clinical outcomes and on process measures. Methods This multicenter, observational, retrospective study included data from pregnant and puerperal adult patients diagnosed with sepsis according to the Surviving Sepsis Campaign guidelines in 2 periods: May 2015 to May 2018 (prebundle) and July 2018 to January 2023 (postbundle). Results Eighty women were included: 24 (30.0%) in the prebundle period and 56 (70.0%) in the postbundle period. The primary source of infection was urinary (40.0%), with Escherichia coli being the most common pathogen isolated from blood cultures. Regarding clinical outcomes, no deaths occurred in pre- and postbundle periods. For mothers, there was no significant difference in median length of stay between the groups, while neonatal intensive care unit admissions of neonates significantly decreased from 85.7% to 31.3% (P = .013). Regarding process measures, the only significant increase occurred in infectious disease specialist consultations in the postbundle period (75.0%) as compared with the prebundle period (50.0%, P = .029). Conclusions The implementation of a regional maternal sepsis management bundle did not significantly alter maternal outcomes but was associated with a reduction in neonatal intensive care unit admissions, although what role bundle implementation had in this change remains uncertain. More infectious disease consultations postbundle highlight the potential role of the bundle increasing sepsis awareness among physicians dealing with these patients. Sepsis is a significant cause of maternal deaths, but early identification and management remain challenging due to the unique physiologic changes in pregnancy. A sepsis management bundle specific to obstetrics was implemented in Lombardy, Italy, aiming to improve sepsis outcomes in pregnant and postpartum women. The study assessed the bundle's impact across 7 hospitals, finding no reduction in maternal intensive care unit admissions or length of hospital stay. The bundle did lead to a significant decrease in neonatal intensive care unit admissions and miscarriage rates, indicating improved clinician awareness of sepsis in this patient population. Despite the mixed results, the study suggests that improved guidelines and education could enhance sepsis management in this population.