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Serena Oliveri,1 Lucilla Lanzoni,1 Serena Petrocchi,1 Rosanne Janssens,2 Elise Schoefs,2 Isabelle Huys,2 Meredith Y Smith,3,4 Ian P Smith,5 Jorien Veldwijk,5,6 G Ardine de Wit,5 Gabriella Pravettoni1 1Applied Research Division for Cognitive and Psychological Science, IEO, European Institute of Oncology IRCCS, Milan, Italy; 2Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium; 3Alexion Pharmaceuticals, Inc., Boston, MA, USA; 4University of Southern California School of Pharmacy, Los Angeles, CA, USA; 5Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands; 6School of Health Policy & Management, Erasmus University Rotterdam, Rotterdam, NetherlandsCorrespondence: Lucilla LanzoniEuropean Institute of Oncology IRCCS, Applied Research Division for Cognitive and Psychological Science, Via Giuseppe Ripamonti, 435, Milano, 20141, ItalyTel +39 294 372054Email lucilla.lanzoni@ieo.itAbstract: The application of web-based and remotely administered surveys is becoming increasingly popular due to the fact that it offers numerous advantages over traditional paper-based or computer-based surveys completed in the presence of the researcher. However, it is unclear whether complex preference elicitation tasks administered online in highly vulnerable patient populations are also feasible. This commentary discusses opportunities and challenges of conducting quantitative patient preference studies in lung cancer patients using web-based modes of data collection. We refer to our recent experience in the context of the Patient Preference in Benefit-Risk Assessments during the Drug Life Cycle (PREFER) project. Among the main advantages were the possibility of reaching a wider and geographically distant population in a shorter timeframe while reducing the financial costs of testing, the greater flexibility offered and the reduced burden on the patients. Some limitations were also identified and should be the object of further research, including the potential lack of inclusiveness of the research, the lack of control over who is completing the survey, a poor comprehension of the study material, and ultimately a lower level of engagement with the study. Despite these limitations, experience from the PREFER project suggests that online quantitative methods for data collection may provide a valuable method to explore preferences in vulnerable patient populations beyond the COVID-19 pandemic.Keywords: discrete choice experiment, swing weighting, web-based survey, educational tool, online data collection, lung cancer

The present study aimed to test a model of relations to ascertain the determinants of distress caused by lockdown for COVID-19. It was hypothesized that the exposure to the COVID-19 increased distress directly and through the mediation of worry, health-related information seeking, and perception of the utility of the lockdown. It was also expected that higher levels of ambiguity intolerance corresponded to higher distress directly and through the mediation of worry, health information seeking behaviors, and perceived utility of the lockdown. Finally, it was expected that risk aversion positively influenced distress directly and through the increasing of worry, health-related information seeking behavior, and more positive perception of the utility of the lockdown The study was conducted in Italy during the mandatory lockdown for COVID-19 pandemic on 240 individuals (age range 18-76). Data recruitment was conducted via snowball sampling. COVID-19 exposure was positively associated with worry and health-related information seeking. Risk-aversion was positively associated with health-related information seeking and perceived utility of the lockdown to contain the spread of the virus. Worry and health-related information seeking were positively associated with distress, whereas the perceived utility of the lockdown was negatively associated with distress. Intolerance for the ambiguity was directly linked to distress with a positive sign. Findings suggest that risk aversion represents both a risk factor and a protective factor, based on what kind of variable mediates the relationship with distress, and that the intolerance to the ambiguity is a risk factor that busters distress., Author(s): S. Petrocchi [sup.1], P. Iannello [sup.2], G. Ongaro [sup.1] [sup.3], A. Antonietti [sup.2], G. Pravettoni [sup.1] [sup.3] Author Affiliations: (1) grid.15667.33, 0000 0004 1757 0843, Applied Research Division for [...]

Abstract Complex chromosome rearrangements are constitutional structural rearrangements involving three or more chromosomes or having more than two breakpoints. These are rarely seen in the general population but their frequency should be much higher due to balanced states with no phenotypic presentation. These abnormalities preferentially occur de novo during spermatogenesis and are transmitted in families through oogenesis. Here, we report a de novo complex chromosome rearrangement that interests eight chromosomes in eighteen-year-old boy with an abnormal phenotype consisting in moderate developmental delay, cleft palate, and facial dysmorphisms. Standard G-banding revealed four apparently balanced traslocations involving the chromosomes 1;13, 3;19, 9;15 and 14;18 that appeared to be reciprocal. Array-based comparative genomic hybridization analysis showed no imbalances at all the breakpoints observed except for an interstitial microdeletion on chromosome 15. This deletion is 1.6 Mb in size and is located at chromosome band 15q14, distal to the Prader-Willi/Angelman region. Comparing the features of our patient with published reports of patients with 15q14 deletion this finding corresponds to the smallest genomic region of overlap. The deleted segment at 15q14 was investigated for gene content.

Highly purified human menopausal gonadotropin (HP-hMG [Menopur ® , Ferring Pharmaceuticals, Saint-Prex, Switzerland]) contains a 1:1 ratio of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). This analysis aimed to assess gonadotropin (FSH, LH and hCG) abundance in HP-hMG and clarify the source of hCG by assessing the presence of sulfated glycans, which are diagnostic for pituitary hCG forms due to their distinct glycosylation patterns. Additionally, the purity of each sample, their specific components, and their oxidation levels were assessed. HP-hMG samples (three of Menopur ® and two of Menogon ® Ferring Pharmaceuticals, Saint-Prex, Switzerland) were included in the current analyses. Brevactid ® (urinary hCG; Ferring Pharmaceuticals, Saint-Prex, Switzerland) and Ovidrel ® (recombinant hCG; Merck KGaA, Darmstadt, Germany) were used as control samples. Glycopeptide mapping and analysis of impurities were carried out by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Oxidation was assessed through reducing peptide mapping using LC-MS/MS. The FSH and LH in the HP-hMG samples showed sulfated glycans, while no signals of sulfated glycopeptides were detected on any site of the beta subunit of hCG. HP-hMG test samples presented the same hCG glycan distribution as the control sample (placental hCG, Brevactid ® ) extracted from the urine of pregnant women, suggesting a non-pituitary source of hCG. Protein impurities were estimated to constitute approximately 20-30% of the entire HP-hMG protein content in the test samples. More than 200 non-gonadotropin proteins were identified in the HP-hMG test samples, of which several were involved in embryonic development or pregnancy. The alpha subunit of the tested samples was strongly oxidized, with a relative abundance of 20% of the total gonadotropin content. Without taking into account all the protein impurities, the beta subunit of LH was detected only in traces (0.9-1.2%) in all tested HP-HMG samples, confirming the data obtained by intact molecule analysis, while high levels of beta hCG (18-47%) were observed. Advanced molecular analysis of HP-hMG indicates a primarily placental origin of hCG, as evidenced by the absence of hCG sulfated glycans and the predominance of placental non-sulfated hCG in LH activity. The analysis revealed 20-30% of protein impurities and a significant presence of oxidized forms in the HP-hMG samples. These findings are critical for understanding the quality, safety, and clinical profile of HP-hMG.

Background: The study examined whether there were linear and curvilinear relationships between the trust beliefs in physicians by the children, those by their mothers and the children's medical health. The study examined whether there were changes in those relationships across time., Methods: The data gathered in a previous study were subjected to further analyses. One hundred and forty-three children with asthma (116 males, M age  = 12 years and 7 months) and their mothers were administered standardized scales twice across 1 year. The scales assessed the children's trust beliefs in physicians, the mothers' trust beliefs in physicians, the children's quality of life and the children's adherence to prescribed medical regimes., Results: Quadratic relationships were found between the children's quality of life and both their and their mothers' trust beliefs in physicians. The quadratic relationship increased over time. Linear relationships were found between trust beliefs in physicians and children's adherence to prescribed medical regimes., Conclusion: Children with asthma are prone to a lower quality of life when they and their mothers hold very high, as well as hold very low, trust beliefs in physicians. Children's trust beliefs in physicians increase the probability of adherence to prescribed medical regimes., (© 2024 The Author(s). Child: Care, Health and Development published by John Wiley & Sons Ltd.)

Increasing evidence has been pointing towards the existence of a bi-directional interplay between mental health condition and immunity. Data collected during the COVID-19 outbreak suggest that depressive symptoms may impact the production of antibodies against SARS-CoV-2, while a previous infection could affect the immune response and cause neuropsychological disturbances. A prospective observational study was designed to investigate the association between mental health conditions and immune response over time. We analyzed the mental health at baseline and the antibodies before and after immunization with the COVID-19 mRNA vaccine in a cohort of healthcare professionals in southern Switzerland. One-hundred and six subjects were enrolled. Anxiety, distress and depression correlated to each other. There were no correlations between the mentioned variables and the vaccine induced IgG antibodies against the receptor binding domain (RBD) of the spike protein. For those who had a previous COVID-19 infection, the antibodies increased according to the grade of depression. For those who did not, the anti-RBD IgG levels remained similar when comparing presence or absence of depression symptoms. Our results show that previous SARS-CoV-2 natural infection in subjects with mental health conditions enhances the immune response to COVID-19 mRNA vaccination. The correlation between immune response to COVID-19 vaccination, a previous exposure to the virus, and symptoms of mood disorders, makes it necessary to explore the direction of the causality between immune response and depressive symptoms., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: There are only two countries in the world (the United States and New Zealand) that allow the pharmaceutical branch to advertise prescription medication directly to consumers. There is pressure on governments to allow direct-to-consumer advertising (DTCA) for prescription drugs elsewhere too. One argument the industry uses frequently is the claim that exposure to DCTA, through various methods and occasions, is supposed to improve customers' knowledge of a disease and treatment. This argument has been part of the health care community's wider discussion of whether DTCA of prescription drugs benefits the population's general interest or is only an attempt to increase the sales of the pharmaceutical branch. Belief in true learning by DTCA is rooted in concepts of empowered consumers and their autonomous and empowered decision-making., Objective: In this study, we tested the hypotheses that contact with DTCA increases recipients' literacy/knowledge, especially regarding the side effects of treatment (hypothesis 1), and empowerment (hypothesis 2). We further hypothesized that DTCA exposure would not increase depression knowledge (ie, about treatments, symptoms, and prevalence) (hypothesis 3)., Methods: A snowball sample of 180 participants was randomly split into three experimental groups receiving (1) a traditional information sheet, (2) a DTCA video clip for an antidepressant prescription drug, or (3) both. The video was original material from the United States translated into Italian for the experiment. Dependent variables were measures of depression knowledge (regarding treatments, symptoms and prevalence, and antidepressant side effects), depression literacy, and empowerment., Results: None of the experimental groups differed significantly from the others in the empowerment measure (hypothesis 2 not confirmed). Partial confirmation of hypothesis 1 was obtained. Lower values on the depression literacy scale were obtained when participants had been given the video compared to the sheet condition. However, the general depression knowledge and its subscale on side effects reached higher scores when participants were exposed to the DTCA, alone or in combination with the information sheet. Finally, participants showed lower scores on knowledge about treatment and symptoms or prevalence after watching the video compared to the sheet condition (hypothesis 3 confirmed). Symptoms and prevalence knowledge increased only when the video was presented in combination with the sheet., Conclusions: There is no evidence for an increase in empowerment following DTCA exposure. An increase in knowledge of the side effects of the medication was observed in the group exposed to the DTCA video. This was the only result that confirmed the hypothesis of the beneficial effect of DTCA videos on knowledge. Written information proved to be the most suitable way to convey knowledge on treatments and symptoms prevalence. Our findings support the necessity of studying health literacy and patient empowerment together and the consequences of such an increase in knowledge in terms of help-seeking behavior., (©Peter Johannes Schulz, Francesca Crosignani, Serena Petrocchi. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 17.07.2023.)

Background: In the treatment of Non-Small Cell Lung Cancer (NSCLC) the combination of Immuno- Oncotherapy (IO) and chemotherapy (CT) has been found to be superior to IO or CT alone for patients' survival. Patients and clinicians are confronted with a preference sensitive choice between a more aggressive treatment with a greater negative effect on quality of life versus alternatives that are less effective but have fewer side effects., Objectives: The aims of this study were to: (a) quantify patients' preferences for relevant attributes related to Immuno-Oncotherapy treatment alternatives, and (b) evaluate the maximum acceptable risk (MAR)/Minimum acceptable benefit (MAB) that patients would accept for treatment alternatives., Methods: An online preference survey using discrete-choice experiment (DCE) was completed by NSCLC patients from two hospitals in Italy and Belgium. The survey asked patients' preferences for five patient- relevant treatment attributes. The DCE was developed using a Bayesian D-efficient design. DCE analyses were performed using mixed logit models. Information regarding patient demographics, health literacy, locus of control, and quality of life was also collected., Results: 307 patients (158 Italian, 149 Belgian), stage I to IV, completed the survey. Patients preferred treatments with a higher 5-year survival chance as the most important attribute over all the other attributes. Preference heterogeneity for the attribute weights depended on health literacy, patients' age and locus of control. Patients were willing to accept a substantially increased risks of developing side effects in exchange for the slightest increase (1%) in the chance of surviving at least 5 years from the diagnosis of cancer. Similarly, patients were willing to accept a switch in the mode of administration or complete loss of hair to obtain an increase in survival., Conclusion: In this study, the proportion of respondents who systematically preferred survival over all other treatment attributes was particularly high. Age, objective health literacy and locus of control accounted for heterogeneity in patients' preferences. Evidence on how NSCLC patients trade between survival and other NSCLC attributes can support regulators and other stakeholders on assessing clinical trial evidence and protocols, based on patients' conditions and socio-demographic parameters., Competing Interests: Author MYS was employed by company Alexion Pharmaceuticals, Inc., Boston, MA, United States. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Oliveri, Lanzoni, Veldwijk, de Wit, Petrocchi, Janssens, Schoefs, Smith, Smith, Nackaerts, Vandevelde, Louis, Decaluwé, De Leyn, Declerck, Petrella, Casiraghi, Galli, Garassino, Girvalaki, Huys and Pravettoni.)

Introduction . The COVID-19 pandemic was recognized as a collective trauma and as a major threat to mental health. Recent literature focused on the stress symptomatology or post-traumatic stress disorder associated to the COVID-19 exposure. The concept that people have a natural inclination toward growth, even under stressful and threatening events, gathered less attention. Previous research has analyzed antecedents of post-traumatic growth (PTG) with non-conclusive results. Methods . The present research aimed at including findings on PTG from personality traits, i.e., sense of control and self-mastery, and distal condition of nurturance and support received by others, i.e., cognitive and affective well-being. Analyses were based on 4934 interviews with adults (M age = 57.81 years, 55.5% women) from the Swiss Household Panel study. Results . Relationships over time emerged between sense of control and self-mastery on PTG and worries, measured after two years, via the mediation of cognitive and affective well-being. Conclusion . Results come from a large study in a design seldom employed in this type of research and can inform both research and interventions., Competing Interests: Competing interestsThe authors have declared that no competing interests exist., (© The Author(s) 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: The COVID-19 outbreak caused severe changes in school activities over the past two years. Teachers underwent a re-planning of their teaching approaches, shifting from face-to-face teaching formats to remote ones. These challenges resulted in high levels of burnout. The identification of risk/protective factors contributing to burnout is crucial in order to inform intervention programs. Thus, we hypothesized a mediation role of teachers' mentalizing ability (processing of emotions, a component of mentalized affectivity) on the relationship between depression, anxiety, and depersonalization (burnout dimension). Two reverse models were computed. Job satisfaction, teachers' age and gender, school grade, and length of teaching experience served as covariates., Methods: 466 (M(sd) = 46.2 (10.4) years) online questionnaires were completed by Italian teachers of primary (n = 204) and middle (n = 242) schools. Measures of burnout, depression, anxiety, and mentalization were administered., Results: The findings corroborated our hypotheses: in all models, processing emotions served as a mediator on the relationship between depression, anxiety, and depersonalization, and on the reciprocal one. Job satisfaction positively impacted processing emotion, and negatively impacted depression and depersonalization; women teachers reported high levels of the anxious trait., Conclusions: Overall, it can be concluded that the ability to mentalize has a beneficial impact on teachers' well-being. Policymaking, clinical, and research implications were discussed.

Cornelia de Lange Syndrome (CdLS) is a rare genetic disorder that affects many organs. The diagnosis of this condition is primarily clinical and it can be confirmed by molecular analysis of the genes known to cause this disease, although about 30% of CdLS patients are without a genetic diagnosis. Here we report clinical and genetic findings of a patient with CdLS type 4, a syndrome of which the clinical features of only 30 patients have been previously described in the literature. The index patient presented with clinical characteristics previously associated with CdLS type 4 (short nose, thick eyebrow, global development delay, synophrys, microcephaly, weight < 2DS, small hands, height < 2DS). She also presented cardiac anomalies, cleft palate and laryngomalacia, which was never described before. The index patient was diagnosed with a novel de novo&nbsp;RAD21 variant (c.1722&#95;1723delTG, p.Gly575SerfsTer2): segregation analysis, bioinformatic analysis, population data and in silico structural modelling indicate the pathogenicity of the novel variant. This report summarizes previously reported clinical manifestations of CdLS type 4 but also highlights new clinical symptoms, which will aid correct counselling of future CdLS type 4 cases.

In the current pandemic situation, psychological science is increasingly considered by public health policy. Empathy is mainly recognized as a crucial drive for prosocial behavior. However, this rich body of evidence still lacks visibility and implementation. Effective social programs are needed, and little is known about how to elicit empathetic drives. The paper gives first a clear foundation to the role of empathy during stressful events. It provides then a comprehensive overview of innovative interventions triggering empathic response in the public such as fiction, film, and theater. Moreover, it integrates interactive ways of sharing personal views that could elicit empathetic feelings in different people. Advances deriving from this perspective could be of significant public interest in the current and future health crises and help authorities develop innovative social programs, which should be the focus of further scientific inquiry., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Grignoli, Filipponi and Petrocchi.)

Disruption in routine may be related to experiencing negative emotional states and to aggressive behaviors in individuals with Autism Spectrum Disorder (ASD). The lockdown because of COVID-19 contributed to the disruption of individuals’ routines, including the sleep−wake cycle. The current study tested a relationship between the adherence to the sleep−wake routine and aggressive behaviors via the mediation role of negative emotional states (i.e., anxiety and anger). Forty-three parents of adults with ASD completed a web-based questionnaire about their life condition during the first lockdown (April−May 2020). Preliminary analyses showed a worsening in the adults’ aggressive behaviors during the lockdown in comparison to before it (Z = −3.130; p = 0.002). In the mediation models, the relationship between the adherence to the sleep−wake routines and aggressive behaviors was significant. The models showed the hypothesized mediated relationships among the adherence to the sleep−wake routines, negative emotional states, and aggressive behaviors (Model 1: F (1, 41) = 10.478, p < 0.001; Model 2: F(1, 41) = 9.826, p = 0.003). The findings confirmed the potential protective role of the adherence to the sleep−wake routines for the emotional and behavioral adjustment of adults with autism. Theoretical and practical contributions of the study were discussed; indeed, our results may inform parent-coaching as well as intervention programs for individuals with ASD given that adequate sleep hygiene may contribute to improvements in internalizing/externalizing behaviors.

Background: This is a registered study protocol on a randomized controlled trial (RCT) testing an intervention aimed to improve men's adherence to evidence-based guidelines on BRCA1/2 germline genetic testing. BRCA1- and BRCA2-associated Hereditary Breast and Ovarian Cancer Syndrome (HBOC) increases the relative and absolute risk of developing breast and ovarian cancer and, to a lesser extent, prostate and pancreatic cancer. Men face BRCA-related cancer risks as women do, although with a different magnitude, and they may also transmit the mutations to their children. Notwithstanding, men are under-tested compared to women and the communication is not tailored on their needs. The present RCT applies principles of the Health Action Process Approach (HAPA) in testing the psychological determinants of the men's adherence to evidence based guidelines on BRCA1/2 germline genetic and testing the efficacy of two messages., Methods: A total of 264 participants will be involved, among the men's relatives of women with verified germline mutations. The study entails a pre- post- evaluation with randomization of the participants in two conditions corresponding to the two messages., Discussion: The expected results provide answers related to the impact of action self-efficacy, outcome expectancy (personal or familiar), risk perception, health risk aversion, intolerance of uncertainty, perceived barriers, and coping self-efficacy on informed decision-making. Data gathered from this study may inform health care providers, policy makers, and public health managers about the communication strategy for men and about the psychological variables influencing decision-making., Trail Registration: Name of the Registry: Clinical Trials. Trial registration number: NCT04683068. Date of registration: 16/12/2020. URL of trial registry record: https://www.clinicaltrials.gov/., Competing Interests: The authors have declared that no competing interests exist.

Instant messaging (IM) is a highly diffused form of communication among younger populations, yet little is known about the emotional experience during IM. The present study aimed to investigate the emotional experience during IM by drawing on the Circumplex Model of Affect and measuring heart rate and electrodermal activity as indicators of arousal in addition to self-reported perceived emotional valence. Using an experimental design, we manipulated message latency (i.e., response after 1 min versus 7 min) and message valence (positive versus negative response). Based on data collected from 65 young adults (50% male; M age = 23.28, SD = 3.75), we observed arousal as participants' electrodermal activity levels increased from the time a fictitious peer started typing a response to the receipt of that response, especially in the delayed condition. Electrodermal activity levels also increased in both the positive and the negative message conditions. No changes were observed for heart rate. Participants' self-report perceived emotional valence revealed that positive messages were evaluated as more pleasant and the peer as more available, while no difference in the self-report was found for message latency. These findings shed light on the emotional experience during IM by adding valuable insights on the physiological processes underlying the anticipation of social reward, but only during delayed IM exchange that can be observed in Human-Computer-Interaction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Camerini, Marciano, Annoni, Ort and Petrocchi.)

BRCA1/2 germline mutations predispose carriers to an increased risk of breast, ovarian, prostate, pancreatic, and skin cancer. Men and women are equally likely to pass on or inherit the pathogenic variant. However, there is evidence that male relatives are less involved in cascade screening than female ones. At the same time, little attention has been given to the research on psychological determinants of men's adherence to cascade screening in BRCA1/2 -positive families. Applying some principles of the Health Action Process Approach model, the present research tested a model of relationships on the adherence to BRCA1/2 cascade testing guidelines. The sample comprised 115 men's first-degree relatives of women with verified germline mutations (Mage = 41.93; SD = 17.27). A pre-post test design was applied. Significant associations emerged between the intention to uptake BRCA1/2 genetic testing and age, parental status, breast cancer risk perception, self-referred outcome expectancies, perceived benefit, coping self-efficacy, and planning. Higher perceived benefit predicted increases in intention, and higher intention and coping self-efficacy predicted increases in planning. Intention was a positive total mediator of the relationship between benefit and planning. On a theoretical level, our findings partially supported the Health Action Process Approach as a valuable model based on which interventions could be developed in the context of cascade screening for BRCA1/2 genetic testing. Those results supported the importance of integrated genetic counselling sessions with a strict collaboration between geneticists and psychologists together with interventions planned to increase men's self-monitoring ability to support their self-efficacy.

Haploinsufficiency of A20 (HA20) is an inflammatory disease caused by mutations in the TNFAIP3 gene classically presenting with Behcet's-like disease. A20 acts as an inhibitor of inflammation through its effect on NF-kB pathway. Here we describe four consanguineous patients (three sisters and their mother) with a predominantly autoimmune phenotype, including thyroiditis, type I diabetes, hemolytic anemia and chronic polyarthritis. All patients had recurrent oral ulcers, with only 1 patient presenting also recurrent fever episodes, as a classical autoinflammatory feature. Next generation sequencing identified a novel heterozygous frameshift mutation (p.His577Alafs*95) that causes a premature stop codon in the zinc finger domain of A20, leading to a putative haploinsufficiency of the protein. Functional analyses confirmed the pathogenicity of the mutation. The variant was associated with decreased levels of A20 in blood cells. Accordingly, ex-vivo lipopolysaccharide (LPS)-stimulated patients' peripheral blood mononuclear cells (PBMCs) showed higher levels of p65 NF-kB phosphorylation, as well as increased production of the proinflammatory cytokines IL-1β, IL-6 and TNF-α. Moreover, in agreement with recent observations, demonstrating a role for A20 in inhibiting STAT1 and IFNγ pathways, markedly higher circulating levels of the two IFNγ-inducible chemokines CXCL9 and CXCL10 were detected in all patients. Supporting the findings of a hyperactivation of IFNγ signaling pathway in HA20 patients, patients' monocytes showed higher levels of STAT1 without stimulation, as well as higher phosphorylated (active) STAT1 levels following IFNγ stimulation. In conclusion, our study show that in the clinical spectrum of HA20 autoimmune features may predominate over autoinflammatory features and demonstrate, from a molecular point of view, the involvement of A20 in modulating not only the NF-kB, but also the IFNγ pathway., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rossi, Federici, Uva, Passarelli, Celani, Caiello, Matteo, Petrocchi, Mortari, De Benedetti, Prencipe and Insalaco.)

In order to explore the psychological impact of the COVID-19 outbreak on the caregiver-child relationship, we investigated the interplay among COVID-19 exposure and children's internalizing/externalizing problems during the Italian lockdown, hypothesizing a mediation effect played by maternal distress. Additionally, we included maternal reflective functioning (i.e., hypermentalization) as a moderator factor among this interplay. A total of 305 Italian mothers of children aged 6-13 years ( M = 10.3; SD = 2.4) filled in an online survey. Findings revealed an indirect effect of maternal COVID-19 exposure on children's anxious/depressed ( k 2 = 0.32) via maternal distress. Hypermentalization moderated the impact of maternal COVID-19 exposure on children's anxious/depressed problems (β = -1.08, k = 0.04). Hypermentalization moderated both the relation between maternal distress and children's aggressive behaviors (β = 12.226; 2 < 0.001) and between maternal distress and children's attention problems (β = 5.617, p < 0.001). We found pivotal significant effects of maternal hypermentalization on children's anxious/depressed and attention problems, indicating that the higher the mother's hypermentalization was, the higher the children's problems were. Our results broaden what we knew on the role of maternal reflective and emotional functioning on children's emotional/behavioral adjustment during stressful situations.p < 0.001) and between maternal distress and children's attention problems (β = 5.617, p < 0.001). We found pivotal significant effects of maternal hypermentalization on children's anxious/depressed and attention problems, indicating that the higher the mother's hypermentalization was, the higher the children's problems were. Our results broaden what we knew on the role of maternal reflective and emotional functioning on children's emotional/behavioral adjustment during stressful situations.

Background: The lung cancer (LC) treatment landscape has drastically expanded with the arrival of immunotherapy and targeted therapy. This new variety of treatment options, each with its own characteristics, raises uncertainty regarding the key aspects affecting patients' health-related quality of life (HRQL). The present qualitative study aimed to investigate how LC patients perceive their HRQL and the factors that they consider to be most influential in determining their HRQL. Methods: This qualitative research incorporates four focus group discussions, with six LC patients in each group. In total, 24 stage III and IV LC patients were included in the discussions, with Italian ( n = 12) and Belgian ( n = 12) patients, age range: 42-78, median age = 62 (IQR = 9.3 years), SD = 8.5; 62% men. Using thematic analysis, transcripts and notes from the FGDs were analyzed using NVivo software (edition 12). Results: Three main themes capturing determinants of HRQL were identified. First, patients agreed on the importance of physical aspects (symptoms and side-effects) in determining their HRQL. In particular, skin conditions, nausea, fatigue, risk of infections, sensory abnormalities, pain, and changes in physical appearance were highlighted. Second, patients worried about psychological aspects, negatively impacting their wellbeing such as uncertainties regarding their future health state, and a lower degree of autonomy and independence. Third, patients underlined the importance of social aspects, such as communication with healthcare providers and social interaction with friends, family and peers. Conclusion: This study demonstrates that physical, psychological, and social aspects are key factors driving LC patients' HRQL. Gaining a better understanding of how LC patients perceive their HRQL and how it is affected by their illness and therapy will aid patient-centric decision-making across the drug life cycle, by providing stakeholders (drug developers, regulators, reimbursement bodies, and clinicians) insights about the treatment and disease aspects of importance to LC patients as well as the unmet needs LC patients may have regarding available treatment modalities. Finally, this study underscores a need for individual treatment decision-making that is considerate of uncertainties among LC patients about their future health state, and ways for improving communication between healthcare providers and patients to do so., Competing Interests: MS was employed by Alexion Pharmaceuticals, Inc at the time of the study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Janssens, Arnou, Schoefs, Petrocchi, Cincidda, Ongaro, Oliveri, Smith, Louis, Vandevelde, Nackaerts, Pravettoni and Huys.)