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The transcription factor Snail is a master regulator of cellular identity and epithelial-to-mesenchymal transition (EMT) directly repressing a broad repertoire of epithelial genes. How chromatin modifiers instrumental to its activity are recruited to Snail-specific binding sites is unclear. Here we report that the long non-coding RNA (lncRNA) HOTAIR (for HOX Transcript Antisense Intergenic RNA) mediates a physical interaction between Snail and enhancer of zeste homolog 2 (EZH2), an enzymatic subunit of the polycomb-repressive complex 2 and the main writer of chromatin-repressive marks. The Snail-repressive activity, here monitored on genes with a pivotal function in epithelial and hepatic morphogenesis, differentiation and cell-type identity, depends on the formation of a tripartite Snail/HOTAIR/EZH2 complex. These results demonstrate an lncRNA-mediated mechanism by which a transcriptional factor conveys a general chromatin modifier to specific genes, thereby allowing the execution of hepatocyte transdifferentiation; moreover, they highlight HOTAIR as a crucial player in the Snail-mediated EMT.

IntroductionRecent theories hypothesized that chonobiological dis-rhythmicity might contribute to Bipolar disorders (BD) by dysregulating most of the systems involved in mood, stress and emotion regulation. In particular, the key role of sleep in regulating stress system and emotions has been hypothesized. Among other important factors contributing to BD the stress vulnerability/resilience dimension may play a key role. In particular low resilience has been associated with a dysregulation in emotions and stress response possibly involved in psychopathological process of BDsObjectivesThe study aimed to investigate the possible impact of resilience and emotion dysregulation on the clinical manifestations of bipolar disorders (BDs) focusing on the possible role of circadian rhythm alterations.MethodsA sample of 197 inpatients suffering from BD of type I (BDI) or II (BDII) were assessed during a major depressive episode using the Structural Clinical Interview for DSM-5 (SCID-5), the Beck Depression Inventory-II (BDI-II), the Young Mania Rating Scale (YMRS), Resilience Scale for Adults (RSA), Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN), Difficulties in Emotion Regulation Scale (DERS) and the Scale for Suicide Ideation (SSI). Participants with or without circadian rhythm disturbances as measured with Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN), were compared; regression and mediation analyses were computed.ResultsParticipants with circadian rhythms disturbances showed a greater severity of depressive symptoms, of suicidal risk, lower resilience and more disturbances in emotion regulation including impulsivity and regulatory strategies. The logistic regression revealed that circadian rhythm disturbances was related to depressive symptoms (O.R. 4.0), suicidal risk (OR 2.51), emotion dysregulation (OR 2.28) and low resilience (OR 2.72). At the mediation analyses, circadian rhythm alterations showed an indirect effect on depressive symptoms by impairing resilience (Z= 3.17, p=0.0014)/ emotional regulation (Z= 4.36, p<0.001) and on suicidal risk by affecting resilience (Z= 2.00, p=0.045) and favoring impulsivity (Z= 2.14, p=0.032).ConclusionsThe present findings may show that circadian rhythm alterations might play a key role in BD manifestations, as being correlated with more severe clinical presentations of depressive symptoms, suicidal risk, impaired resilience and emotional dysregulation. Addressing circadian rhythm alterations might potentially promote resilience and emotion regulation hence improving mood symptoms and suicidal risk in BDs.Disclosure of InterestNone Declared

IntroductionBpolar disorder (BD) is a severe and chronic psychiatric disorder it is the sixth leading cause of disability among all illnesses worldwide. With regard to causes of premature mortality, patients with BD are at very high risk of suicide. Whereas risk factors for suicidal behaviors are multiple and complex, hopelessness appears to be a major independent risk factor for suicidality in BD. Compelling evidence has also demonstrated that BD is frequently associated with circadian rhythms alteration, contributing to its vulnerability, pathogenesis, and manifestations. in particular in the desynchronization of sleep and social life, has been associated with the severity of BD. Indeed hopelessness has never been studid in relation to circadian rhythms in BDObjectivesTo examine the role of chronobiological rhythm alterations in suicidal ideation and behaviors and its relation with hopelessness.MethodsOne hundred twenty-seven patients (77 females, mean age of 47.4 ± 12.5 years) with a major depressive episode and bipolar disorder (BD) type I or II (according to Structured Clinical Interview for DSM-5 assessment) were recruited in 2019 and assessed for depressive and manic symptoms (Beck Depression Inventory-II, Young Mania Rating Scale) and with the Biological Rhythms Interview of Assessment in Neuropsychiatry, Beck Hopelessness Scale, and Scale for Suicide Ideation. Univariate regression and mediation analyses were performed.ResultsForty-one patients (32.3%) showed clinically significant suicidal ideation and were more frequently affected by BD type I (P = .029) with mixed features (P = .022). Compared to nonsuicidal individuals, they had significantly more depressive symptoms (P = .019), higher emotional component of hopelessness (P = .037), and higher dysrhythmicity of sleep (P = .009), activities (P = .048), and social life (P = .019). Passive and active suicidal ideation and suicidal plans were best predicted by dysrhythmicity of sleep and social life. Dysrhythmicity of sleep and social life mediated the direct effect of depressive symptoms on passive and active suicidal ideation and also of active ideation on suicidal plans. The emotional component of hopelessness was related to dysrhythmicity of social life and mediated its effect on suicidal plans (P = .010).ConclusionsChronobiological alterations directly contributed to passive and active suicidal ideation and to suicidal preparation, with a key role of circadian rhythm alteration of sleep, activities, and social life. Chronobiological alterations also impacted the emotional component of hopelessness, hence indirectly contributing to suicidal ideations and plans. These findings call for the systematic screening of these dysrhythmicity dimensions when considering suicidal risk in individuals with BD.Disclosure of InterestNone Declared

Although a significant subset of prostate tumors remain indolent during the entire life, the advanced forms are still one of the leading cause of cancer-related death. There are not reliable markers distinguishing indolent from aggressive forms. Here we highlighted a new molecular circuitry involving microRNA and coding genes promoting cancer progression and castration resistance. Our preclinical and clinical data demonstrated that c-Met activation increases miR-130b levels, inhibits androgen receptor expression, promotes cancer spreading and resistance to hormone ablation therapy. The relevance of these findings was confirmed on patients’ samples and by in silico analysis on an independent patient cohort from Taylor’s platform. Data suggest c-Met/miR-130b axis as a new prognostic marker for patients’ risk assessment and as an indicator of therapy resistance. Our results propose new biomarkers for therapy decision-making in all phases of the pathology. Data may help identify high-risk patients to be treated with adjuvant therapy together with alternative cure for castration-resistant forms while facilitating the identification of possible patients candidates for anti-Met therapy. In addition, we demonstrated that it is possible to evaluate Met/miR-130b axis expression in exosomes isolated from peripheral blood of surgery candidates and advanced patients offering a new non-invasive tool for active surveillance and therapy monitoring.

Subject-specific finite element models have been used to predict stress-state and fracture risk in individual patients. While many studies analysed quasi-axial loading configurations, only few works simulated sideways load configurations, such as those arising in a fall. The majority among these latter directly predicted bone strength, without assessing elastic strain prediction accuracy. The aim of the present work was to evaluate if a subject-specific finite element modelling technique from CT data that accurately predicted strains in quasi-axial loading configurations is suitable to accurately predict strains also when applying low magnitude loads in sideways configurations. To this aim, a combined numerical–experimental study was performed to compare finite element predicted strains with strain-gauge measurements from three cadaver proximal femurs instrumented with sixteen strain rosettes and tested non-destructively under twelve loading configurations, spanning a wide cone (0–30° for both adduction and internal rotation angles) of sideways fall scenarios. The results of the present study evidenced a satisfactory agreement between experimentally measured and predicted strains (R2 greater than 0.9, RMSE% lower than 10%) and displacements. The achieved strain prediction accuracy is comparable to those obtained in state of the art studies in quasi-axial loading configurations. Still, the presence of the highest strain prediction errors (around 30%) in the lateral neck aspect would deserve attention in future studies targeting bone failure.

The way death is (not) dealt with is one of the main determinants of the current crisis of cancer care. The tendency to avoid discussions about terminal prognoses and to create unrealistic expectations of fighting death is seriously harming patients, families and healthcare professionals, and the delivery of high-quality and equitable care. Drawing on different literature sources, we explore key dimensions of the taboo of death: medical, policy, cultural. We suggest that the oncologist, from a certain moment, could take on the role of amicus mortis , a classical figure in the past times, and thus accompanying patients towards the end of their life through palliation and linking them to psychosocial and ethical/existential resources. This presupposes the implementation of Supportive Care in Cancer and the ethical idea of relational autonomy based on understanding patients’ needs considering their sociocultural contexts. It is also key to encourage public conversations beyond the area of medicine to re-integrate death into life.

Background Aim of the study was to enrol a group of individuals with schizophrenia in a long-term moderate-intensity physical activity program and to evaluate its effects on their cognitive functions and cardiovascular risk factors. An additional aim of the study was the comparison of the adherence to the physical activity program before and during the COVID-19 pandemic. Methods Forty sedentary patients diagnosed with schizophrenia (mean age 46.4 ± 9.6) followed by the Public Mental Health Department of Ferrara were included in the study. 28 of them followed a 1-year walking program consisting of two guided walking sessions/week, while 12 maintained their sedentary lifestyle and followed the usual Cognitive Rehabilitation program. To the participants following the walking program VO 2 peak and walking speed were assessed at baseline and at the end of the program. All participants were evaluated on blood pressure and anthropometric variable. Cognitive functions were assessed with the Screen for Cognitive Impairment in Psychiatry (SCIP) and with the Frontal Assessment Battery (FAB) questionnaires. Results The 20 participants completing the walking program displayed significant improvements in cognitive functions (d ppc2 0.35 for SCIP and 0.26 for FAB), with a positive correlation between SCIP score and the number of sessions attended (R = 0.86, p  < 0.001), evident in the patients attending to at least 75 of the 100 walking sessions. Walking speed and VO 2 peak increased significantly and a decrease of body weight, BMI, systolic and diastolic blood pressure was also observed. The adherence to the walking program registered during Covid-19 period did not differ from that observed before the pandemic. The 12 CG (Control Group) patients maintaining the sedentary lifestyle did not display improvements of cognitive functions. Conclusions The main finding of this study is the improvement of cognitive functions which is significantly related to the number of walking sessions attended by participants with schizophrenia. The walking program, guided by exercise specialists, proved to be an enjoyable activity for people with mental disorder feasible even during the COVID-19 pandemic. Trial registration Retrospectively registered on ISRCTN as non-randomized trial (n. ISRCTN14763786).

Trabecular bone is viscoelastic under dynamic loading. However, it is unclear how tissue viscoelasticity controls viscoelasticity at the apparent-level. In this study, viscoelasticity of cylindrical human trabecular bone samples (n=11, male, age 18–78 years) from 11 proximal femurs were characterized using dynamic and stress-relaxation testing at the apparent-level and with creep nanoindentation at the tissue-level. In addition, bone tissue elasticity was determined using scanning acoustic microscope (SAM). Tissue composition and collagen crosslinks were assessed using Raman micro-spectroscopy and high performance liquid chromatography (HPLC), respectively. Values of material parameters were obtained from finite element (FE) models by optimizing tissue-level creep and apparent-level stress-relaxation to experimental nanoindentation and unconfined compression testing values, respectively, utilizing the second order Prony series to depict viscoelasticity. FE simulations showed that tissue-level equilibrium elastic modulus (Eeq) increased with increasing crystallinity (r=0.730, p=.011) while at the apparent-level it increased with increasing hydroxylysyl pyridinoline content (r=0.718, p=.019). In addition, the normalized shear modulus g1 (r=−0.780, p=.005) decreased with increasing collagen ratio (amide III/CH2) at the tissue-level, but increased (r=0.696, p=.025) with increasing collagen ratio at the apparent-level. No significant relations were found between the measured or simulated viscoelastic parameters at the tissue- and apparent-levels nor were the parameters related to tissue elasticity determined with SAM. However, only Eeq, g2 and relaxation time τ1 from simulated viscoelastic values were statistically different between tissue- and apparent-levels (p<.01). These findings indicate that bone tissue viscoelasticity is affected by tissue composition but may not fully predict the macroscale viscoelasticity in human trabecular bone.

The chamois Rupicapra spp. is the most abundant mountain ungulate of Europe and the Near East, where it occurs as two species, the northern chamois R. rupicapra and the southern chamois R. pyrenaica. Here, we provide a state‐of‐the‐art overview of research trends and the most challenging issues in chamois research and conservation, focusing on taxonomy and systematics, genetics, life history, ecology and behavior, physiology and disease, management and conservation. Research on Rupicapra has a longstanding history and has contributed substantially to the biological and ecological knowledge of mountain ungulates. Although the number of publications on this genus has markedly increased over the past two decades, major differences persist with respect to knowledge of species and subspecies, with research mostly focusing on the Alpine chamois R. r. rupicapra and, to a lesser extent, the Pyrenean chamois R. p. pyrenaica. In addition, a scarcity of replicate studies of populations of different subspecies and/or geographic areas limits the advancement of chamois science. Since environmental heterogeneity impacts behavioral, physiological and life history traits, understanding the underlying processes would be of great value from both an evolutionary and conservation/management standpoint, especially in the light of ongoing climatic change. Substantial contributions to this challenge may derive from a quantitative assessment of reproductive success, investigation of fine‐scale foraging patterns, and a mechanistic understanding of disease outbreak and resilience. For improving conservation status, resolving taxonomic disputes, identifying subspecies hybridization, assessing the impact of hunting and establishing reliable methods of abundance estimation are of primary concern. Despite being one of the most well‐known mountain ungulates, substantial field efforts to collect paleontological, behavioral, ecological, morphological, physiological and genetic data on different populations and subspecies are still needed to ensure a successful future for chamois research and conservation.

. In a fusion-evaporation reaction, nuclei are produced by evaporating light-charged particles and neutrons from the compound nucleus. Typically, a nucleus of interest is produced as a result of a part of the total cross-section and, in order to guarantee a good channel discrimination, a particle detector, like the EUCLIDES 4 π Si-ball array, is necessary. EUCLIDES has been quoted in more than a hundred publications resulting from many experiments performed in combination with the EUROBALL and GASP γ -ray spectrometers. The present paper reports on the upgraded version of EUCLIDES, that is presently coupled to the new GALILEO γ -ray spectrometer, installed at the Laboratori Nazionali di Legnaro, INFN. The design, characteristics and performance of the EUCLIDES array are presented and discussed.