Confirmatory validation of the Mesothelioma Psychological Distress Tool-Patients: A brief patient-reported outcome measure assessing psychological distress in malignant mesothelioma patients.

OBJECTIVE: Psychological suffering in patients with Malignant Mesothelioma (MM) is different from the one experienced by patients with other cancers due to its occupational or environmental etiology and its peculiar symptomatology and prognosis (i.e., poor prognosis, reduced effectiveness of the therapies, poor quality of residual life, and advanced age at the time of diagnosis). Therefore, the Mesothelioma Psychological Distress Tool-Patients (MPDT-P) has been developed to evaluate the specific profile of psychological suffering in this population. This paper describes the item selection, factor analysis, and psychometric evaluation of the revised MPDT-P. METHODS: The analyses of the current work aimed to confirm the factorial structure found in the first version of the MPDT-P. In the case of nonfit, it aimed to find an alternative structure and causes of nonfit in the model. The search for the fit of the factorial model was conducted using a Bayesian approach. RESULTS: The two-factor model reported in the first version of the instrument did not fit the data. Confirmatory Bayesian analyses showed adequate fit for the three-factor solution. Based on the content of the items, we labeled the factors as dysfunctional emotions, claims for justice, and anxieties about the future. CONCLUSIONS: Integrating the MPDT-P into clinical practice could help clinicians gain insight into the specific suffering related to MM and investigate potential differences related to different occupational and environmental exposure contexts.

Meta-analysis of the Difficulties in Emotion Regulation Scale and its short forms: A two-part study.

The Difficulties in Emotion Regulation Scale (DERS) is the most used self-report questionnaire to assess deficits in emotion regulation (ER), composed of 6 dimensions and 36 items. Many studies have evaluated its factor structure, not always confirming the original results, and proposed different factor models. A possible way to try to identify the dimensionality of the DERS could be through a meta-analysis with structural equation models (MASEM) of its factor structure. The MASEM indicated that a six-factor model with 32 items (DERS-32) was the most suitable to represent the dimensionality of the DERS (χ2 = 2095.96, df = 449, p < .001; root mean square error of approximation [RMSEA] = 0.024, 95% confidence interval [CI]: 0.023-0.025; comparative fit index [CFI] = 0.97; Tucker Lewis index [TLI] = 0.96; standardized root mean squared residual [SRMR] = 0.04). This result was also confirmed by a confirmatory factor analysis (χ2 = 3229.67, df = 449, p < 0.001; RMSEA = 0.075, 95% CI: 0.073-0.078; CFI = 0.94; TLI = 0.93; SRMR = 0.05) on a new sample (1092 participants; mean age: 28.28, SD = 5.82 years) recruited from the Italian population. Analyses and results from this sample are reported in the second study of this work. The DERS-32 showed satisfactory internal consistency (i.e., ordinal α, Molenaar Sijtsma statistic, and latent class reliability coefficient) for all its dimensions and correctly categorized individuals with probable borderline symptomatology. In conclusion, the DERS-32 has demonstrated to be the best model for the DERS among all the others considered in this work, as well as a reliable tool to assess deficits in ER.

Psychometric Properties of the Detachment and Compartmentalization Inventory (DCI) in an Italian Community Sample.

The Detachment and Compartmentalization Inventory (DCI) is a valid and reliable self-report instrument that assesses these two distinct forms of dissociative symptoms. However, there is limited research on the cross-cultural validation of the DCI. Therefore, this study aimed to develop an Italian translation of the DCI and examine its internal structure and psychometric properties (including internal consistency, convergent validity, and test-retest reliability) within an Italian-speaking community sample. The sample consisted of 1276 adults (887 females; mean age: 29.57 ± 10.96 years), who completed the DCI and other self-report measures evaluating dissociative experiences and childhood trauma. Confirmatory factor analyses supported the original two-factor model (χ2169 = 1312.80, RMSEA = 0.073, 95%CI 0.069-0.077; CFI = 0.94; TLI = 0.94; SRMR = 0.04). Additionally, the DCI exhibited good internal consistency, test-retest reliability, and convergent validity with another measure of dissociation. The study also confirmed the association between DCI scores and the severity of childhood trauma. Finally, a Receiver Operating Characteristic (ROC) curve analysis demonstrated that the DCI effectively distinguishes individuals who screened positively for dissociative disorders. Overall, these findings indicate that the Italian translation of the DCI possesses satisfactory psychometric properties, suggesting its utility as a screening tool for assessing detachment and compartmentalization experiences.

Psychometric Properties of the Italian Mentalization Questionnaire: Assessing Structural Invariance and Construct Validity.

Mentalization is an important interpersonal ability, necessary for adaptive interpersonal relationships and emotion regulation. Deficits in mentalization have been associated with poor psychological outcomes and have been observed in patients with Borderline Personality Disorder. The Mentalization Questionnaire (MZQ) has been developed as self-report measure of mentalization deficit. The aim of the study was to investigate the dimensionality of the MZQ in a nonclinical sample composed of Italian adults from the general population and to analyze its performance in categorizing individuals with higher risk of borderline symptoms. A non-clinical sample of 1,015 adults (709 women and 306 men) was administered the Italian versions of the MZQ, the Reflective Functioning Questionnaire (RFQ), and a measure of borderline psychopathology. A revised single-factor solution fitted the data well and demonstrated metric invariance across gender. The internal consistency (Ordinal α = 0.87) and stability (r = 0.84) were satisfactory. The MZQ was moderately associated with the RFQ dimensions. The ROC curve analysis showed that the MZQ was able to discriminate satisfactorily people with higher risk for borderline symptomatology from those with lower risk. The MZQ may, therefore, be considered a reliable and valid measure of mentalization for categorizing people at higher risk for borderline pathology.

Germline Mutations in FAF1 Are Associated With Hereditary Colorectal Cancer.

BACKGROUND & AIMS: A significant proportion of colorectal cancer (CRC) cases have familial aggregation but little is known about the genetic factors that contribute to these cases. We performed an exhaustive functional characterization of genetic variants associated with familial CRC. METHODS: We performed whole-exome sequencing analyses of 75 patients from 40 families with a history of CRC (including early-onset cases) of an unknown germline basis (discovery cohort). We also sequenced specific genes in DNA from an external replication cohort of 473 families, including 488 patients with colorectal tumors that had normal expression of mismatch repair proteins (validation cohort). We disrupted the Fas-associated factor 1 gene (FAF1) in DLD-1 CRC cells using CRISPR/Cas9 gene editing; some cells were transfected with plasmids that express FAF1 missense variants. Cells were analyzed by immunoblots, quantitative real-time polymerase chain reaction, and functional assays monitoring apoptosis, proliferation, and assays for Wnt signaling or nuclear factor (NF)-kappa-B activity. RESULTS: We identified predicted pathogenic variant in the FAF1 gene (c.1111G>A; p.Asp371Asn) in the discovery cohort; it was present in 4 patients of the same family. We identified a second variant in FAF1 in the validation cohort (c.254G>C; p.Arg85Pro). Both variants encoded unstable FAF1 proteins. Expression of these variants in CRC cells caused them to become resistant to apoptosis, accumulate beta-catenin in the cytoplasm, and translocate NF-kappa-B to the nucleus. CONCLUSIONS: In whole-exome sequencing analyses of patients from families with a history of CRC, we identified variants in FAF1 that associate with development of CRC. These variants encode unstable forms of FAF1 that increase resistance of CRC cells to apoptosis and increase activity of beta-catenin and NF-kappa-B.

The association between adult ADHD and food addiction: A mediation analysis.

OBJECTIVES: The aim of this study was to investigate the association between food addiction severity (FA) and ADHD symptomatology. Furthermore, we investigated whether emotional distress, and the mentalization deficits could mediate this relationship. METHODS: Three hundred eighty-five Italian adults (307 women and 78 men) participated in the study and completed the Italian versions of the Modified Yale Food Addiction Scale version 2.0, the Adult ADHD Self-Report Scale, the Depression Anxiety Stress Scales 21 and the Mentalization Questionnaire. RESULTS: ADHD symptoms severity and general distress were significantly and independently associated with FA. Emotional distress partly mediated the relationship between FA and ADHD symptoms severity. In addition, mentalization deficits partly mediated this relationship only when evaluating the influence of FA on ADHD symptoms severity. LIMITATIONS: This is a cross-sectional study and causal interpretations of the relationships among the variables are speculative. CONCLUSIONS: It is important to assess emotional distress and mentalization deficits in individuals at risk of ADHD and FA because these conditions could increase the risk for the presence of disordered eating patterns.

Bioselection Reveals miR-99b and miR-485 as Enhancers of Adenoviral Oncolysis in Pancreatic Cancer.

Oncolytic viruses are designed for cancer treatment. Cell-virus interactions are key determinants for successful viral replication. Therefore, the extensive reprogramming of gene expression that occurs in tumor cells might create a hurdle for viral propagation. We used a replication-based approach of a microRNA (miRNA) adenoviral library encoding up to 243 human miRNAs as a bioselection strategy to identify miRNAs that facilitate adenoviral oncolytic activity in pancreatic ductal adenocarcinoma. We identify two miRNAs, miR-99b and miR-485, that function as enhancers of adenoviral oncolysis by improving the intra- and extracellular yield of mature virions. An increased adenoviral activity is the consequence of enhanced E1A and late viral protein expression, which is probably mediated by the downregulation of the transcriptional repressors ELF4, MDM2, and KLF8, which we identify as miR-99b or miR-485 target genes. Arming the oncolytic adenovirus ICOVIR15 with miR-99b or miR-485 enhances its fitness and its antitumoral activity. Our results demonstrate the potential of this strategy to improve oncolytic adenovirus potency, and they highlight miR-99b and miR-485 as sensitizers of adenoviral replication.

Psychometric properties of the modified Yale Food Addiction Scale Version 2.0 in an Italian non-clinical sample.

PURPOSE: To assess the dimensionality and psychometric properties of the modified Yale Food Addiction Scale 2.0 (mYFAS 2.0) in an Italian non-clinical sample. METHODS: 262 adults (184 women) were administered the Italian versions of the mYFAS 2.0, and questionnaires measuring binge eating severity, anxiety and depression symptoms, and emotional dysregulation. RESULTS: 15 individuals (5.7%) met the criteria for a diagnosis of food addiction according to the mYFAS 2.0. Bayesian confirmatory factor analysis supported a single-factor solution for the mYFAS 2.0. The mYFAS 2.0 had good internal consistency (Ordinal α = 0.91), and convergent validity with binge eating severity (r = 0.67, p < 0.001), both anxiety (r = 0.31, p < 0.001) and depressive (r = 0.35, p < 0.001) symptoms, and difficulties in emotion regulation (r = 0.35, p < 0.001). Finally, both discriminant validity with dietary restraint (Gamma = 0.11; p = 0.52) and incremental validity in predicting binge eating severity over emotion dysregulation and psychopathology (b = 0.52; t = 11.11; p < 0.001) were confirmed. CONCLUSIONS: The Italian mYFAS 2.0 has satisfactory psychometric properties and can be used as a brief instrument for the assessment of addictive eating behaviors when time constraints prevent the use of the original version. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

A mesenchymal-like phenotype and expression of CD44 predict lack of apoptotic response to sorafenib in liver tumor cells.

The multikinase inhibitor sorafenib is the only effective drug in advanced cases of hepatocellular carcinoma (HCC). However, response differs among patients and effectiveness only implies a delay. We have recently described that sorafenib sensitizes HCC cells to apoptosis. In this work, we have explored the response to this drug of six different liver tumor cell lines to define a phenotypic signature that may predict lack of response in HCC patients. Results have indicated that liver tumor cells that show a mesenchymal-like phenotype, resistance to the suppressor effects of transforming growth factor beta (TGF-ß) and high expression of the stem cell marker CD44 were refractory to sorafenib-induced cell death in in vitro studies, which correlated with lack of response to sorafenib in nude mice xenograft models of human HCC. In contrast, epithelial-like cells expressing the stem-related proteins EpCAM or CD133 were sensitive to sorafenib-induced apoptosis both in vitro and in vivo. A cross-talk between the TGF-ß pathway and the acquisition of a mesenchymal-like phenotype with up-regulation of CD44 expression was found in the HCC cell lines. Targeted CD44 knock-down in the mesenchymal-like cells indicated that CD44 plays an active role in protecting HCC cells from sorafenib-induced apoptosis. However, CD44 effect requires a TGF-ß-induced mesenchymal background, since the only overexpression of CD44 in epithelial-like HCC cells is not sufficient to impair sorafenib-induced cell death. In conclusion, a mesenchymal profile and expression of CD44, linked to activation of the TGF-ß pathway, may predict lack of response to sorafenib in HCC patients.

Attention-Deficit/Hyperactivity Disorder and Unhealthy Lifestyle in Adolescence: Unforeseen Role of Allostatic Overload and Psychological Well-Being.

Unhealthy lifestyle behaviors (ULBs) are common in early adolescence and could be worsened by Attention-Deficit/Hyperactivity Disorder (ADHD), as well as by specific psychosocial factors, such as stress and unbalanced (i.e., too high or low scores of) psychological well-being (PWB) dimensions. This multi-center study aimed to evaluate how interactions between ADHD symptoms and psychosocial factors associated with ULBs (i.e., Allostatic Overload and multidimensional Psychological Well-Being), considered as moderators, could affect the adoption of ULBs during adolescence. A total of 440 fourteen-year-old adolescents were recruited from six upper secondary schools in Bologna and Rome (Italy) and completed self-report questionnaires on ULBs, ADHD, and psychosocial factors. Relations between ADHD symptomatology and specific ULBs (i.e., impaired sleep, problematic Internet use) were moderated by variables deemed as "negative" (i.e., Allostatic Overload) or "positive" (i.e., PWB dimensions of Self-Acceptance, Personal Growth, Positive Relations, Purpose in Life, Environmental Mastery): when the "negative" moderator is absent and the levels of the "positive" moderators are higher, ULBs decrease among students with lower ADHD symptomatology but increase among students with more severe ADHD. Based on ADHD severity, interventions should aim at promoting a state of euthymia, which consists in balanced PWB dimensions and reflects the optimal level of well-being to fulfill one's own potential and self-realization.

Behavioral Lifestyle Interventions for Weight Loss in Overweight or Obese Patients with Type 2 Diabetes: A Systematic Review of the Literature.

PURPOSE OF REVIEW: Around 80-90% of patients with type 2 diabetes mellitus (T2DM) are overweight or obese, presenting a greater risk for serious health complications and mortality. Thus, weight loss represents a main goal for T2DM management. Although behavioral lifestyle interventions (BLIs) could help promoting weight loss in T2DM patients with overweight or obesity, their effectiveness is still controversial. This systematic review offers an updated and comprehensive picture of BLIs according to Michie's classification in T2DM patients with overweight or obesity and identifies possible factors (related to both patients and interventions) associated with weight loss. The PRISMA guidelines were followed. The literature search till March 2023 indicated 31 studies involving 42 different BLIs. RECENT FINDINGS: Our findings suggest that structured BLIs, characterized by frequent feedback and support, can lead to a clinically meaningful 5% weight loss, regardless of specific behavioral, diet, and physical activity components. Further research should address methodological issues and heterogeneity of interventions, also considering the effect of pharmacological therapies on weight reduction. Lastly, more attention should be paid to the long-term effectiveness of behavioral lifestyle interventions and to the relationship between weight loss and diabetes.

Development of the acne-specific quality of life questionnaire Quality of Life Relevance-Acne.

Background: Participating members of the European Academy of Dermatology and Venereology Task Forces on quality of life (QoL) and Patient Oriented Outcomes and Acne, Rosacea and Hidradenitis Suppurativa initiated data collection in 9 European countries and formed the list of the most relevant topics for acne patients. Objective: The aim of this study was to develop a new acne-specific health-related QoL instrument based on the list of the most relevant topics for acne patients. Methods: After assessment by acne patients (n = 715) on how clear and relevant the items in the prototype questionnaire were, a group of experts on acne and QoL performed discussions on items inclusion, which resulted in a series of 21 items. Then another group of acne patients (n = 1502) filled in the new version of the instrument. A factor analysis was conducted on the 21-item version. Results: Three-factor model with 19 items indicated a satisfactory fit. The three dimensions were called: Socioemotional; Symptoms; Stigma and Suicidal thoughts. Limitations: Included patients and experts may not fully represent acne patients and health care professionals worldwide. Conclusion: A final 19-item version of the Quality of Life Relevance-Acne was developed.

Item-specific patterns of the Skindex-17 in individuals with different levels of Hidradenitis Suppurativa severity: a network analysis study.

Background: Recent studies are stressing the idea that the level of Hidradenitis Suppurativa (HS) severity does not always correspond to the same illness load. In fact, it was found that there was no significant association between Skindex-17 and clinical severity of HS, and that some items of the Skindex-17 might be more related to HS severity than others. Objective: The aim of the current study was to explore the associations between different levels of clinical severity of HS (mild, moderate, severe) and the Skindex-17 single-item responses in a large sample of adults patients. Methods: A cross-sectional study with a sample include 547 consecutive HS patients, approaching for the first time the specific dermatologic evaluation. Eligible criteria included age ≥ 18 years, HS diagnosis formulated contextually by the same expert clinician, and providing informed consent. All participants completed the Skindex-17 and were evaluated for the disease clinical severity with the International Hidradenitis Suppurativa Severity Score System. A Network Analysis was conducted, which represents a powerful methodological approach in clinical research. It allows to study specific patterns and the structure of complex system in order to better understand how the elements of the system interact with each-other. Three different Network Analyses were conducted for each group of HS clinical severity by including the items of the Skindex-17 as the nodes of each network. Results: Among 547 patients, 40% (219) were female and mean age was of 32.70 (±11.41). Different patterns among items of the Skindex-17 for the three clinical severity groups emerged, meaning that in each group different items are more crucial than others. The psychosocial subscale of the Skindex-17 is the most relevant when assessing the Quality of Life of individuals with different levels of HS severity, however, with the progression of the disease, individuals place attention also on two different aspects of the symptoms subscale of the Skindex-17, irritation and pain, which in turn perfectly reflect the severity of HS, from a clinical perspective. Conclusion: These results provide new insights on the association between levels of HS severity and related Quality of Life, measured with the Skindex-17.

Italian Validation of the Short Version of the Failure to Mentalize Trauma Questionnaire in Adults at Risk Due to Childhood Trauma.

The impact of recurrent traumatic experiences during childhood may impede the integration of mentalization abilities and lead to psychopathology. Recently, the Failure to Mentalize Trauma Questionnaire (FMTQ), a comprehensive 29-item self-report scale aimed at identifying deficits in mentalization arising from childhood trauma, was developed. However, the length of the FMTQ may render it impractical for epidemiological studies involving multiple variables and measures. Furthermore, the initial testing revealed inadequate factor reliabilities for the two first-order factors. Therefore, this study aimed to shorten and create a unidimensional version (FMTQ-s) and investigate its psychometric properties, including internal consistency and convergent and concurrent validity, in a non-clinical Italian adult sample. The factor analysis supported a 13-item unidimensional version of the FMTQ with acceptable internal consistency (ordinal alpha = 0.88) and satisfactory convergent and concurrent validity. The FMTQ-s obtained scalar invariance between individuals with and without self-reported childhood traumas. Overall, the FMTQ-s appears to be a feasible and reliable tool for assessing deficits in mentalization resulting from childhood trauma.

Interface Diffusion and Compatibility of (Ba,La)FeO3-δ Perovskite Electrodes in Contact with Barium Zirconate and Ceria.

Ba1-xLaxFeO3-δ perovskites (BLF) capable of conducting electrons, protons, and oxygen ions are promising oxygen electrodes for efficient solid oxide cells (fuel cells or electrolyzers), an integral part of prospected large-scale power-to-gas energy storage systems. We investigated the compatibility of BLF with lanthanum content between 5 and 50%, in contact with oxide-ion-conducting Ce0.8Gd0.2O2-δ and proton-conducting BaZr0.825Y0.175O3-δ electrolytes, annealing the electrode-electrolyte bilayers at high temperature to simulate thermal stresses of fabrication and prolonged operation. By employing both bulk X-ray diffraction and synchrotron X-ray microspectroscopy, we present a space-resolved picture of the interaction between electrode and electrolyte as what concerns cation interdiffusion, exsolution, and phase stability. We found that the phase stability of BLF in contact with other phases is correlated with the Goldschmidt tolerance factor, in turn determined by the La/Ba ratio, and appropriate doping strategies with oversized cations (Zn2+, Y3+) could improve structural stability. While extensive reactivity and/or interdiffusion was often observed, we put forward that most products of interfacial reactions, including proton-conducting Ba(Ce,Gd)O3-δ and mixed-conducting (Ba,La)(Fe,Zr,Y)O3-δ, may not be very detrimental for practical cell operation.

The EU-funded I3LUNG Project: Integrative Science, Intelligent Data Platform for Individualized LUNG Cancer Care With Immunotherapy.

Although immunotherapy (IO) has changed the paradigm for the treatment of patients with advanced non-small cell lung cancers (aNSCLC), only around 30% to 50% of treated patients experience a long-term benefit from IO. Furthermore, the identification of the 30 to 50% of patients who respond remains a major challenge, as programmed Death-Ligand 1 (PD-L1) is currently the only biomarker used to predict the outcome of IO in NSCLC patients despite its limited efficacy. Considering the dynamic complexity of the immune system-tumor microenvironment (TME) and its interaction with the host's and patient's behavior, it is unlikely that a single biomarker will accurately predict a patient's outcomes. In this scenario, Artificial Intelligence (AI) and Machine Learning (ML) are becoming essential to the development of powerful decision-making tools that are able to deal with this high-complexity and provide individualized predictions to better match treatments to individual patients and thus improve patient outcomes and reduce the economic burden of aNSCLC on healthcare systems. I3LUNG is an international, multicenter, retrospective and prospective, observational study of patients with aNSCLC treated with IO, entirely funded by European Union (EU) under the Horizon 2020 (H2020) program. Using AI-based tools, the aim of this study is to promote individualized treatment in aNSCLC, with the goals of improving survival and quality of life, minimizing or preventing undue toxicity and promoting efficient resource allocation. The final objective of the project is the construction of a novel, integrated, AI-assisted data storage and elaboration platform to guide IO administration in aNSCLC, ensuring easy access and cost-effective use by healthcare providers and patients.

Biomicroscopy versus optical coherence tomography screening of epiretinal membranes in patients undergoing cataract surgery.

PURPOSE: The purpose of the study is the evaluation and comparison of the relative incidence of epiretinal membrane in patients undergoing cataract surgery diagnosed with biomicroscopy versus those diagnosed with optical coherence tomography imaging (Stratus). METHODS: This prospective study evaluated 146 eyes of patients referred for cataract surgery. Considering biomicroscopic fundus appearance assessed by two examiners and OCT, the following findings were considered to indicate positivity for epiretinal membranes: biomicroscopic evidence of cellophane macular reflex, biomicroscopic evidence of macular pucker, and OCT thickening of the vitreoretinal interface with or without loss of the foveal depression. Positivity (metamorphopsia) to original Amsler test was also noted. RESULTS: Patient mean age was 72.8 ± 9.1 years. Optical coherence tomography revealed 17 eyes with macular pucker (11.6%) and 21 with cellophane macular reflex (14.4%) and, hence, a total of 38 eyes with epiretinal membrane (26%; confidence interval, 18.9-33.1%). Biomicroscopy evaluation overlooked 14 affected eyes, or 9.6% of the eyes examined. False negatives, that is, eyes affected by epiretinal membrane (cellophane macular reflex or macular pucker) and not detected biomicroscopically were 36.8% (confidence interval, 21.5-52.2.7%) and false positives were 1.9% (confidence interval, 0-4%). Amsler test was positive in 7 (18.4%) of the 38 affected eyes. CONCLUSION: This study finds that patients undergoing cataract surgery may present with epiretinal membrane that are better detected by optical coherence tomography rather than by biomicroscopy. Optical coherence tomography was more sensitive both for eyes with cellophane macular reflex and for those with macular pucker. The use of this instrument before surgery can therefore be considered.

Testing some psychometric properties of the Italian version of the Skin Cancer Index: A questionnaire for measuring quality of life in patients with non-melanoma skin cancer.

Objectives: Non-melanoma skin cancers (NMSC) include two main types: basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). Generic Health-Related Quality of Life (HRQoL) instruments revealed little to no HRQoL impairment in NMSC patients. Instead, the use of specific skin disease HRQoL tools contradicted those observations. For example, the Skin Cancer Index (SCI) was suggested as a validated instrument for the evaluation of the impact of skin cancers on HRQoL, and has already been validated in several languages, but not in Italian. The aim of this study is to testing some psychometric properties of the Italian version of the SCI questionnaire in a large sample of NMSC patients. Methods: This is a cross-sectional, single-center, observational study. Firstly, different factor models proposed in the literature were compared and the model with the best fit was identified. Secondly, the psychometric properties of the SCI, convergent validity and reliability, were evaluated. Results: The sample was composed of 371 NMSC patients. The factor analysis revealed that a revised version of the original model had the best fit [χ2(df = 85) = 354.53, p < 0.001, RMSEA = 0.09, CFI = 0.98, TLI = 0.97, SRMR = 0.03]. The SCI had satisfactory internal consistency for all subscales (Emotional subscale: ordinal alpha = 0.95; Social subscale: ordinal alpha = 0.94; Appearance subscale: ordinal alpha = 0.94). The convergent validity with Skindex-17 psychosocial subscale was adequate for all the SCI subscales (Emotional Subscale: rho = -0.50; Social Subscale: rho = -0.54; Appearance subscale: rho = -0.44; Total Skin Cancer Index: rho = -0.56; and p < 0.001). Conclusion: The tested psychometric properties of the Italian version of the SCI may suggest that it is an appropriate tool to measure the HRQoL in NMSC patients, however, further studies are needed in order to confirm and tested other psychometric features of this tool.

Inhibition of miR-222 by Oncolytic Adenovirus-Encoded miRNA Sponges Promotes Viral Oncolysis and Elicits Antitumor Effects in Pancreatic Cancer Models.

Oncolytic adenoviruses (OA) are envisioned as a therapeutic option for patients with cancer, designed to preferentially replicate in cancer cells. However, the high number of genetic alterations in tumors can generate a context in which adenoviruses have difficulties replicating. Abnormal miRNAs expression is a trademark of pancreatic cancer, with several oncogenic miRNAs playing essential roles in cancer-associated pathways. The perturbed miRNome induces reprogramming of gene expression in host cells that can impact the complex interplay between cellular processes and viral replication. We have studied the effects of overexpressed miRNAs on oncolytic adenoviral activity and identified miRNAs modulators of adenoviral oncolysis in pancreatic cancer cells. Inhibition of the highly upregulated miR-222 sensitized cancer cells to oncolysis. To provide a therapeutic application to this insight, we engineered the oncolytic adenovirus AdNuPARmE1A with miR-222 binding sites, working as sponges to withdraw the miRNA from the cellular environment. AdNuPAR-E-miR222-S mediated-decrease of miR-222 expression in pancreatic cancer cells strongly improved the viral yield and enhanced the adenoviral cytotoxic effects. Antitumoral studies confirmed a high activity for AdNuPARmE1A-miR222-S in vivo, controlling tumor progression more effectively than the scrambled control virus in xenografts. We demonstrated that the increased antitumor potency of the novel oncolytic virus resulted from the combinatory effects of miR-222 oncomiR inhibition and the restoration of miR-222 target genes activity enhancing viral fitness.