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Abstract Background Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. Methods In this study, 382 infants born at 24+0–27+6 weeks’ gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks’ postmenstrual age. The secondary outcomes are BPD at 36 weeks’ postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). Discussion This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0–27+6 weeks’ gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks’ postmenstrual age of life. Trial registration ClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

Self-regulatory self-efficacy belief (i.e., SRSE) represents a fundamental factor for adjustment in adolescence, as a vehicle to promote positive behaviors and protect youths from transgressions and maladjustment. Research attested that, during adolescence, boys are more vulnerable to externalizing behaviors than girls, especially when they perceive themselves as scarcely capable of managing and orienting their behaviors and when they possess impairments in impulsivity. Previous studies firmly supported the crucial role of SRSE, especially in the offline context in adolescence. Still, very few studies investigated its impact in the online context, although nowadays, the Internet represents one of the most significant environments for youths’ daily lives. Thus, we aimed to examine the protective moderating role of SRSE in online and offline aggressive behaviors beyond youths’ temperamental vulnerabilities, such as high impulsivity. A sample of 318 Italian adolescents (Mage = 15.21; SD = 0.51; 57% boys; 40% girls; 3% third gender) were asked to complete the Impulsivity Scale at Wave 1, online and offline aggressive behaviors scales at Wave 2, and SRSE at Wave 2. The multiple-group-by-gender moderation model evidenced that, for what concerns online aggression, beyond the direct effects of impulsivity in boys and girls, SRSE directly affected online aggression and mediated the effect of impulsivity in girls. In contrast, impulsivity significantly affected offline aggressive behaviors only indirectly through the impact of SRSE, and SRSE directly influenced these behaviors in both genders. These results hold for the effects of youth’s age, sexual orientation, socioeconomic status, and years of education completed. This work preliminary evidenced that, contrary to previous studies which focused mainly on the vulnerability of boys to aggressive conduct, impulsivity had direct effects on online aggressive behaviors in girls, and SRSE can protect adolescents of both genders in the online context by predicting low online aggression and represents a protective factor from the indirect effects that impulsivity impairments can also have in the offline context.

IntroductionLimited research focused on the association between parenting practices and children’s prosocial and externalizing behaviors comparing same- and different-gender parent families. The present study considered 76 Italian families (73% same-gender and 27% different-gender parent families) with 8-year-old (SD = 2.17; 49% assigned female at birth) children born through assisted reproductive techniques, to explore parenting practices and children’s prosocial and externalizing behaviors.MethodWe ran a Multiple-group-by-couple Structural Equation Model in which we estimated the predictive role of parenting on children’s behaviors, controlling for age, gender, and family socioeconomic status using the Maximum Likelihood estimation.ResultsResults showed that both same- and different-gender parent families reported high levels of parental warmth and very low levels of hostility and rejection; regarding children’s behaviors, both same- and different-gender parent families reported high levels of prosociality and low levels of externalizing behaviors. In addition, same-gender parents reported significantly higher levels of children’s prosociality and parental warmth than different-gender parents. Regarding associations between parenting practices and behaviors, we found a positive association between positive parenting practices and increasing children’s prosocial behaviors and decreasing children’s externalizing behaviors, in both same- and different-gender families, controlling for family background characteristics.ConclusionThe present study encourages future research to investigate how specific parenting practices can influence behavioral adjustment in children, focusing on same-gender parent families.

Bullying and cyberbullying represent pervasive issues in adolescence because they are very common situations with significant implications for concurrent and later adjustment. It is crucial to investigate the extent to which youths’ personality characteristics may represent a vulnerability to becoming (cyber)bullies or (cyber)victims. However, research mostly has focused on associations with single personality dimensions rather than overall functioning patterns, studies on personality profiles in relation to bullying are limited and under-examined, and no evidence for cyberbullying is available. Within Latent Profile Analysis (i.e., LPA), the present study aimed to identify personality profiles in a sample of 426 Italian early adolescents (Mage = 12; 51 % female), according to the Big Five Model (i.e., Extraversion-E, Agreeableness-A, Conscientiousness-C, Emotional Stability-ES, Openness-O), in connection with traditional bullying and cyberbullying roles (i.e., uninvolved, victims, bullies, bullies/victims). Three profiles emerged with specific associations with (cyber)bullying roles: (1) Resilient (with high scores in all traits) which tended to be uninvolved; (2) Undercontrolled (with low C, average-to-high E, and average-to-low ES, and O), which was more likely to be both bullies and victims, both offline and online; and (3) Overcontrolled (with very low E, average C, and average-to-low ES and O), which was more likely to be associated with traditional (but not online) victimization. The results fill a research gap, demonstrating that specific youths’ personality configurations may be associated with different roles in traditional and online bullying.

IntroductionThis longitudinal study examined unique and joint effects of parenting and negative emotionality in predicting the growth curves of adolescents’ self-efficacy beliefs about regulating two discrete negative emotions (anger and sadness) and the association of these growth curves with later maladjustment (i.e., internalizing and externalizing problems).MethodsParticipants were 285 children (T1: Mage = 10.57, SD = 0.68; 53.3% girls) and their parents (mothers N = 286; fathers N = 276) from Colombia and Italy. Parental warmth, harsh parenting, and internalizing and externalizing problems were measured in late childhood at T1, whereas early adolescents’ anger and sadness were measured at T2 (T2: Mage = 12.10, SD = 1.09). Adolescent self-efficacy beliefs about anger and sadness regulation were measured at five time-points from T2 to T6 (T6: Mage = 18.45, SD = 0.71), and internalizing and externalizing problems were measured again at T6.ResultsMulti-group latent growth curve models (with country as the grouping variable) demonstrated that in both countries there was on average a linear increase in self-efficacy about anger regulation and no change or variation in self-efficacy about sadness regulation. In both countries, for self-efficacy about anger regulation (a) T1 harsh parenting and T1 externalizing problems were negatively associated with the intercept, (b) T2 anger was negatively associated with the slope, and (c) the intercept and the slope were associated with lower T6 internalizing and externalizing problems, controlling for T1 problems. For self-efficacy about sadness regulation, (a) T1 internalizing problems were negatively associated with the intercept only in Italy, (b) T2 sadness was negatively associated with the intercept only in Colombia, and (c) the intercept negatively predicted T6 internalizing problems.DiscussionThis study advances knowledge of the normative development of self-efficacy beliefs about anger and sadness regulation during adolescence across two countries, highlighting the predictive value of pre-existing family and individual characteristics on this development and prediction by the development of self-efficacy beliefs on later adjustment.

Self-regulatory self-efficacy belief (i.e., SRSE) represents a fundamental factor for adjustment in adolescence, as a vehicle to promote positive behaviors and protect youths from transgressions and maladjustment. Research attested that, during adolescence, boys are more vulnerable to externalizing behaviors than girls, especially when they perceive themselves as scarcely capable of managing and orienting their behaviors and when they possess impairments in impulsivity. Previous studies firmly supported the crucial role of SRSE, especially in the offline context in adolescence. Still, very few studies investigated its impact in the online context, although nowadays, the Internet represents one of the most significant environments for youths' daily lives. Thus, we aimed to examine the protective moderating role of SRSE in online and offline aggressive behaviors beyond youths' temperamental vulnerabilities, such as high impulsivity. A sample of 318 Italian adolescents (Mage = 15.21; SD = 0.51; 57% boys; 40% girls; 3% third gender) were asked to complete the Impulsivity Scale at Wave 1, online and offline aggressive behaviors scales at Wave 2, and SRSE at Wave 2. The multiple-group-by-gender moderation model evidenced that, for what concerns online aggression, beyond the direct effects of impulsivity in boys and girls, SRSE directly affected online aggression and mediated the effect of impulsivity in girls. In contrast, impulsivity significantly affected offline aggressive behaviors only indirectly through the impact of SRSE, and SRSE directly influenced these behaviors in both genders. These results hold for the effects of youth's age, sexual orientation, socioeconomic status, and years of education completed. This work preliminary evidenced that, contrary to previous studies which focused mainly on the vulnerability of boys to aggressive conduct, impulsivity had direct effects on online aggressive behaviors in girls, and SRSE can protect adolescents of both genders in the online context by predicting low online aggression and represents a protective factor from the indirect effects that impulsivity impairments can also have in the offline context. [ABSTRACT FROM AUTHOR]

In a Hilbert space X, we consider the abstract problem [Please download the PDF to view the mathematical expression] where L is a closed linear operator in X and M [member of] [??](X) is not necessarily invertible, z [member of] X. Given the additional information [PHI][My(t)] = g(t) with [PHI] [membr of] [X.sup.*], g [member of] [C.sup.1] ([0, [tau]]; [??]), we are concerned with the determination of the conditions under which we can identify f [member of] C([0,[tau]];C) such that y be a strict solution to the abstract problem, i.e., My [member of] [C.sup.1] ([0,[tau]]; X), Ly [member of] C([0,[tau]];X). A similar problem is considered for general second-order equations in time. Various examples of these general problems are given., CONTENTS 1. Introduction and Basic Notations 583 2. Equations of the First Order. The Multivalued Operators Approach 584 3. The General Case 588 4. Equations of the Second Order in [...]

The present study examines parents' self-efficacy about anger regulation and irritability as predictors of harsh parenting and adolescent children's irritability (i.e., mediators), which in turn were examined as predictors of adolescents' externalizing and internalizing problems. Mothers, fathers, and adolescents (N = 1,298 families) from 12 cultural groups in 9 countries (China, Colombia, Italy, Jordan, Kenya, Philippines, Sweden, Thailand, and United States) were interviewed when children were about 13 years old and again 1 and 2 years later. Models were examined separately for mothers and fathers. Overall, cross-cultural similarities emerged in the associations of both mothers' and fathers' irritability, as well as of mothers' self-efficacy about anger regulation, with subsequent maternal harsh parenting and adolescent irritability, and in the associations of the latter variables with adolescents' internalizing and externalizing problems. The findings suggest that processes linking mothers' and fathers' emotion socialization and emotionality in diverse cultures to adolescent problem behaviors are somewhat similar.

Parental self-efficacy (PSE) captures parents' beliefs in their ability to perform the parenting role successfully and to handle pivotal issues of specific developmental periods. Although previous studies have shown that, across the transition to adolescence, parents show decreasing levels of PSE while adolescents exhibit increasing engagement in rule-breaking (RB) behaviors, there is a paucity of studies investigating whether and how changes in PSE are related to late adolescents' RB behaviors across development. The present study examined the developmental trends of PSE among Italian mothers and fathers over seven waves (representing children's transition from late childhood to late adolescence; approximately from 9 to 18 years old) as well as the longitudinal associations between PSE and RB behaviors during late adolescence. Data were drawn from seven waves of the Parenting Across Cultures (PAC) project, a large-scale longitudinal, cross-cultural study, and included 200 Italian children (MAgeAtTime1 = 9.80, SD = 0.65; 50.5% girls) and their parents (200 mothers; 190 fathers). PSE was measured across all seven time-points (from T1 to T7), while adolescents' RB behaviors were measured at the first and last assessment (T1 and T7). Results of univariate latent growth models showed a cubic trend of mothers' PSE, which revealed a decreasing pattern characterized initially by a slight decline, followed by a rebound before continuously decreasing. By contrast, fathers' PSE followed a linear decrease over time. Finally, our findings evidenced that only the slope of mothers' PSE negatively predicted adolescents' RB behaviors at T7, implying that mothers who maintained higher levels of PSE over time had children who later engaged in lower RB behaviors. The study implications are discussed.

Abstract Background Synovial sarcoma (SS) is an aggressive soft tissue tumor with limited therapeutic options in advanced stage. SS18-SSX fusion oncogenes, which are the hallmarks of SS, cause epigenetic rewiring involving histone deacetylases (HDACs). Promising preclinical studies supporting HDAC targeting for SS treatment were not reflected in clinical trials with HDAC inhibitor (HDACi) monotherapies. We investigated pathways implicated in SS cell response to HDACi to identify vulnerabilities exploitable in combination treatments and improve the therapeutic efficacy of HDACi-based regimens. Methods Antiproliferative and proapoptotic effects of the HDACi SAHA and FK228 were examined in SS cell lines in parallel with biochemical and molecular analyses to bring out cytoprotective pathways. Treatments combining HDACi with drugs targeting HDACi-activated prosurvival pathways were tested in functional assays in vitro and in a SS orthotopic xenograft model. Molecular mechanisms underlying synergisms were investigated in SS cells through pharmacological and gene silencing approaches and validated by qRT-PCR and Western blotting. Results SS cell response to HDACi was consistently characterized by activation of a cytoprotective and auto-sustaining axis involving ERKs, EGR1, and the β-endoglycosidase heparanase, a well recognized pleiotropic player in tumorigenesis and disease progression. HDAC inhibition was shown to upregulate heparanase by inducing expression of the positive regulator EGR1 and by hampering negative regulation by p53 through its acetylation. Interception of HDACi-induced ERK-EGR1-heparanase pathway by cell co-treatment with a MEK inhibitor (trametinib) or a heparanase inhibitor (SST0001/roneparstat) enhanced antiproliferative and pro-apoptotic effects. HDAC and heparanase inhibitors had opposite effects on histone acetylation and nuclear heparanase levels. The combination of SAHA with SST0001 prevented the upregulation of ERK-EGR1-heparanase induced by the HDACi and promoted caspase-dependent cell death. In vivo, the combined treatment with SAHA and SST0001 potentiated the antitumor efficacy against the CME-1 orthotopic SS model as compared to single agent administration. Conclusions The present study provides preclinical rationale and mechanistic insights into drug combinatory strategies based on the use of ERK pathway and heparanase inhibitors to improve the efficacy of HDACi-based antitumor therapies in SS. The involvement of classes of agents already clinically available, or under clinical evaluation, indicates the transferability potential of the proposed approaches.

Background: Neurodevelopmental disorders comprise a clinically and genetically heterogeneous group of conditions that affect 2%–5% of children and represents a public health challenge due to complexity of the etiology. Only few patients with unexplained syndromic and non-syndromic NDDs receive a diagnosis through first-tier genetic tests as array-CGH and the search for FMR1 CGG expansion. The aim of this study was to evaluate the clinical performance of a targeted next-generation sequencing (NGS) gene panel as a second-tier test in a group of undiagnosed patients with NDDs.Method: A 221-gene next-generation sequencing custom panel was designed and used to analyze a cohort of 338 patients with a broad spectrum of NDDs (202 males and 136 females) including Intellectual Disability (ID), Autism Spectrum Disorders (ASD), Epilepsy, language and motor disorders.Results: A molecular diagnosis was established in 71 patients (21%) and a de novo origin was present in 38 (64.4%) of the available trios. The diagnostic yield was significantly higher in females than in males (29.4% vs. 15.3%; p = 0.0019) in particular in ASD (36.8% vs. 7.6%; p = 0.0026) and Epilepsy (38.9% vs. 14.4% p = 0.001). The most involved genes were SLC2A1, SCN1A, ANKRD11, ATP1A2, CACNA1A, FOXP1, and GNAS altered in more than two patients and accounting for the 19.7% of the diagnosis.Conclusion: Our findings showed that this NGS panel represents a powerful and affordable clinical tool, significantly increasing the diagnostic yield in patients with different form of NDDs in a cost- and time-effective manner without the need of large investments in data storage and bioinformatic analysis.

We describe an extension of previous results on degenerate abstract equations described by Favini and Yagi in their monograph cited in the references.This allows us to study degenerate differential equations with fractional derivative in time. Both direct and relative inverse problems are studied. Finally, various applications to degenerate partial differential equations are described.

The negative impact of the COVID-19 pandemic on individuals’ psychosocial functioning was widely attested during the last year. However, the extent to which individual differences are associated with adaptive and maladaptive outcomes during quarantine in Italy remains largely unexplored. Using a person-oriented approach, the present study explored the association of personality profiles, based on three broad individual dispositions (i.e., positivity, irritability, and hostile rumination) and two self-efficacy beliefs in the emotional area (i.e., expressing positive emotions and regulating anger emotion), with adaptive and maladaptive outcomes during the first Italian lockdown (March–June 2020). In doing so, we focused also on how different age groups (i.e., young adults and adults) differently faced the pandemic. The study was conducted through an online survey from May to June 2020 and included 1341 participants living in Italy, divided into two groups: 737 young adults aged 18–35 and 604 adults aged 36–60 years old. Latent Profile Analysis identified three personality profiles: resilient, vulnerable, and moderate. A subsequent path analysis model showed that the resilient profile was positively associated with prosocial behavior as an indicator of adaptive outcome, and negatively associated with three maladaptive outcomes: interpersonal aggression, depressive symptoms, and anxiety problems. Contrarily, the vulnerable profile resulted negatively associated with prosocial behavior and positively associated with the three maladaptive outcomes. Finally, regarding age group differences, young adults belonging to the vulnerable profile showed a greater association especially with interpersonal aggression, depression, and anxiety problems, as compared to adults belonging to the same profile. Overall, the results of the present study highlighted the importance to analyze individual functioning during an isolation period by using a person-oriented approach. Findings evidenced the existence of three different profiles (i.e., Resilient, Vulnerable, and Moderate) and subsequent path analysis revealed, especially for the vulnerable profile and young adults, a greater maladaptive consequence of the quarantine. The practical implications will be discussed.

A total of 63 myeloproliferative neoplasms [MPN; 9 polycythemia vera (PV), 32 essential thrombocythemia (ET), and 22 myelofibrosis (MF)] underwent spleen stiffness (SS) measurement by vibration-controlled transient elastography equipped with a novel spleen-dedicated module. Higher SS values significantly correlated with grade 2-3 bone marrow (BM) fibrosis (p=0.035), with hemoglobin level

BIRC3 is a recurrently mutated gene in chronic lymphocytic leukemia (CLL) but the functional implications of BIRC3 mutations are largely unexplored. Furthermore, little is known about the prognostic impact of BIRC3 mutations in CLL cohorts homogeneously treated with first-line fludarabine, cyclophosphamide, and rituximab (FCR). By immunoblotting analysis, we showed that the non-canonical nuclear factor-κB pathway is active in BIRC3-mutated cell lines and in primary CLL samples, as documented by the stabilization of MAP3K14 and by the nuclear localization of p52. In addition, BIRC3-mutated primary CLL cells are less sensitive to flu-darabine. In order to confirm in patients that BIRC3 mutations confer resistance to fludarabine-based chemoimmunotherapy, a retrospective multicenter cohort of 287 untreated patients receiving first-line FCR was analyzed by targeted next-generation sequencing of 24 recurrently mutated genes in CLL. By univariate analysis adjusted for multiple comparisons BIRC3 mutations identify a poor prognostic subgroup of patients in whom FCR treatment fails (median progression-free survival: 2.2 years, P

Background: Youths' online problematic behaviors, such as smartphone or social network sites (SNS) addiction, gained increasing attention nowadays, due to their impact on concurrent and later adjustment, such as emotional and/or behavioral problems, academic impairments, or relational issues. Aims: This study aims to evaluate the effectiveness of a pilot school‐based intervention to contrast online addictive behaviors while fostering adolescents' self‐regulative abilities. Materials & Methods: The intervention started in January 2022 in an Italian junior high school located in Rome, and consisted of four meetings with students. A total sample of 462 15‐year‐old adolescents (Mage = 15.2; SD = 0.50; 41% females; Ncontrol = 214; Nintervention = 248) was considered. Within the latent difference score framework, we examined short‐term changes from the pre‐to‐the‐postintervention levels of SNS and smartphone addiction, and self‐regulatory self‐efficacy (SRSE) beliefs as a possible booster of the intervention's effectiveness. Results: Results showed a significant decrease in both online addictions (SNS and smartphone addiction), controlling for age, gender, sexual orientation, and socioeconomic status, because of the short‐term efficacy of the project. The buffering effect of SRSE beliefs was further supported. Conclusion: These findings emphasized the usefulness of promoting youths' self‐regulative beliefs to contrast problematic tendencies, according to a Positive Youth Development perspective which focused on resources rather than only on the prevention of negative outcomes for youths' adjustment. [ABSTRACT FROM AUTHOR]