Yanda, China

AI-driven Narrow-band Imaging Score for Disease Assessment and Outcome Prediction in Ulcerative Colitis

This is a multicentre prospective international study. This study aims at developing a new simple endoscopic score using white light endoscopy - high definition (WLE-HD), Texture and colour enhancement imaging (TXI), red dichromatic imaging (RDI) and narrow-band imaging (NBI) modes, focusing on vascular features to distinguish between quiescent versus patchy mild Ulcerative Colitis. It will evaluate the new score's diagnostic performance in defining disease activity/remission compared to existing endoscopic and histological scores and predict long-term clinical outcomes. Finally, it also aims to develop and adapt existing artificial intelligence (AI) algorithms according to WLE-HD, TXI, RDI and NBI to grade and standardize endoscopic and histological disease assessment and predict long-term clinical outcomes. The study will be divided in several phases: - In the first phase, the score will be developed on the first 30 consecutive virtual electronic chromoendoscopy (VCE) videos (using TXI-RDI and NBI) of UC patients, with different grade of disease activity. Experts in inflammatory bowel disease (IBD) endoscopy will review images and videos from recruited patients to define the endoscopic mucosal and vascular features of the new score. These will be used for a stepwise discussion. A round table discussion using modified Delphi method will be conducted by experts worldwide to ensure equal participation and identify the best component descriptors of endoscopic vascular healing. The components that will achieve 100% consensus will be selected, and the most important endoscopy predictive variables will be confirmed by using a machine learning technique. Finally, a new endoscopic score will be generated. This should be reproducible, valid and responsive. - In the second phase, the new endoscopic scoring system will be validated in a large cohort of UC patients, focusing on patients with quiescent disease versus patchy mild colitis. Diagnostic accuracy, interobserver agreement and ability to predict clinical outcome according to the new endoscopic score focused on vascular features assessed with VCE will be evaluated - In the third phase, the reproducibility of the new endoscopic scoring system will be evaluated among gastroenterologists with different levels of experience through a short survey and a computerised training module. - In the fourth phase, new and existing AI algorithms will be developed and adapted to these endoscopic videos and histological images to grade and standardize endoscopic and histological disease assessment and predict long-term clinical outcome in UC.

Educational Motivational Program on Sleep Apnea

The study aims to introduce a specific motivational intervention for patients with Obstructive Sleep Apnea (OSA) starting CPAP adaptation, aimed at improving sleep quality and disease management through good adherence to treatment. Additionally, the study will investigate adherence to the proposed treatment in both groups, using average daily use as an adherence indicator, defined as the total hours of CPAP divided by the total number of observation days. Secondary objectives include investigating the effectiveness of the motivational treatment on subjective sleep quality compared to the control group and assessing whether there are statistically significant differences between the clinical practice group (Control Group - GC) and the Experimental Group (GS) in terms of daytime sleepiness (ESS), sleep quality (PSQI), disease perceptions (B-IPQ), and quality of life related to the disease (SF-12). Inclusion criteria are adult patients with OSA (mild, moderate, severe) who are beginning their adaptation process to CPAP and can understand the Italian language. Exclusion criteria include minors, patients already adapted to CPAP, and those unable to understand the Italian language. During the ME-CA study at the Sleep Center, participants will undergo the following procedures to evaluate adaptation to CPAP therapy and its impacts on sleep quality and quality of life. Participants will have an initial evaluation with a pulmonologist in an outpatient setting at the Sleep Center (according to standard clinical practice). They will complete questionnaires to collect socio-demographic data, disease perception, daytime sleepiness, sleep quality, quality of life, and service usability at three different times: at enrollment (T0), one week after the intervention (T1), and three months after the conclusion of the intervention (T2). The adaptation process will follow the assigned protocol (GS or GC); specifically, the Experimental Group will receive a four-phase psychological-motivational intervention in addition to standard CPAP adaptation. Phase 1 (Pre-adaptation psychoeducation): Within two days prior to the home visit by the provider, which typically occurs within three days of the visit with the pulmonologist, participants will be shown an educational video on OSA (25 minutes) and provided with necessary supplies (device, masks, and tubing). Phase 2 (Motivational Interview): After the first night of titration and CPAP use, participants will be contacted for a brief motivational interview (25 minutes). Phase 3 (Psychological Support Interview): One week after the provider's intervention and the start of CPAP adaptation, participants will be contacted for a support interview (40 minutes), as the first week of adaptation is considered a high-risk period for abandoning device use. Phase 4 (Monitoring Interview): Two weeks after the provider's intervention and the beginning of CPAP adaptation, participants will be contacted for a monitoring interview (30 minutes) to ensure no difficulties or issues have arisen during the adaptation process. The frequency and duration of the CPAP adaptation will span a total of 16 days. During this period, participants in the Experimental Group (GS) will engage in four distinct phases, each involving specific meetings or evaluations totaling 120 minutes of participation. These will include psychoeducational sessions, motivational interviews, psychological support, and monitoring. The Control Group (GC), on the other hand, will follow the standard CPAP adaptation pathway without additional meetings or interventions during the initial 15-day adaptation period. Participants in the control group will follow the standard CPAP adaptation pathway. After the visit with the pulmonologist responsible for the Sleep Center, patients in the control group will be offered adaptation to CPAP therapy. They will then be contacted by the provider to arrange a home visit, usually within three days of the visit with the pulmonologist, during which the necessary supplies (device, masks, and tubing) will be provided. Following this, there will be a 15-day adaptation period during which the patient will use the device without further contact with medical staff or the provider. At the end of this period, if the patient has shown adequate adaptability to CPAP therapy, the physician will proceed with the final prescription of the device.

Multidisciplinary Network OSA Code (Obstructive Apnea Syndrome): Digital Operative Model in Public Health for an Early Diagnosis and Therapy Monitoring

Epithelioid Haemangioendothelioma Observational Study

Epithelioid hemangioendothelioma (EHE) is an ultra-rare (incidence rate < 1/1000.000), translocated, vascular soft tissue sarcoma. It shows a pick of incidence in the 4th decade of life, and it is more commonly diagnosed in females, with reported disease onset during pregnancy. Two specific translocations have been identified in EHE, representing an hallmark in diagnosis today: the fusion of Transcriptional Co-activator with a PDZ-motif (TAZ) with Calmodulin Binding Transcription Activator 1 (CAMTA1) which is present in almost 90 % of cases, and the fusion of Yes-associated Protein (YAP) and Transcription Factor E3 (TFE3) genes (YAP-TFE3), which can be found in around 10% of the patients. YAP and TAZ are well-defined downstream effectors in the Hippo pathway. Forced activation of YAP/TAZ is thought to drive EHE and contribute to key aspects of the cancer phenotype, including metastasis and fibrosis. Most of the times, EHE presents as multifocal or metastatic at diagnosis, with lung, liver and bone being the more commonly involved. The clinical course ranges from cases naturally stable over time to those highly aggressive and rapidly fatal. Pleural effusion, lymph node metastases and pathologic features (nuclear pleomorphism, mitotic figures and presence of necrosis) have been reported to be associated with a worse outcome, but biological and molecular predictors are still lacking. In particular, there is a subgroup of EHE presenting with serosal involvement, typically associated with chronic mild fever, weight loss, asthenia, anorexia, severe disease- related pain, (more responsive to anti-inflammatory pain killers that morphine), and dyspnoea which seems to perform very poorly. The biological basis sustaining this presentation is completely unknown. As of today, there are no reports available in literature providing a comprehensive description of the peculiar EHE radiological features, both for primary and metastatic disease at different sites, and their potential prognostic role has not been explored. In addition, there are no published data to indicate the optimal routine follow-up policy of surgically treated EHE patients with localised disease and the routine follow-up schedules differ across institutions. The appropriate frequency of imaging in cases suffering of distant metastases is also left to be determined. Also, the definition of radiological progression and the assessment of treatment response in EHE remain major challenges. The appearance or worsening of serosal effusion, the changes in serosal involvement and the limited increase in size over a short-time interval in slow-growing variants are not promptly captured by Response Evaluation Criteria for Solid Tumor (RECIST) definition for disease progression. This makes the use of such criteria unsatisfactory in this complex disease and could potentially lead to a delay in progression recognition and treatment start. Similarly, being frequently observed in EHE under treatment, improvement of serosal effusion, reduction in size <30%, and correlation between radiology and symptoms should be taken into account when assessing treatment response. Surgery is the mainstay of care in the local setting. Active surveillance can be a reasonable strategy for patients with naturally stable or asymptomatic, slowly progressive disease, reserving medical treatment to symptomatic or progressive cases. Data on conventional chemotherapy in advanced EHE are limited to case reports and single-institution experiences and suggest a limited role for the drugs commonly used in adult-type soft tissue sarcomas. Signs of activity have been reported with the use of anti-angiogenics, including pazopanib, sorafenib, bevacizumab, alone or in combination with chemotherapy, and apatinib. Due to the peculiar natural history of the disease, the value of antiangiogenics and/or immunomodulatory agents has also been explored, with responses described with sirolimus, thalidomide, interferon, and celecoxib. In absence of any active treatment available, EHE is a neglected disease, and the identification of new potentially active compounds, especially for patients affected by the more aggressive EHE variant. To this end, it looks to be of major importance to identify what is behind disease progression, the "inflammatory-like" disease presentation, and the prevalence of the disease in the female young population. Several lines of evidence have highlighted the significance of inflammation at the local and/or systemic level in human tumor pathobiology. Indeed, inflammation can influence tumor progression, metastasis and therapeutic outcome by establishing a tumor supportive immune microenvironment. These processes are mediated through a variety of cytokines and hormones that exert their biological actions either locally or distantly via systemic circulation. Estrogen signaling is mediated via several receptor proteins. In addition to the classical ERα and ERβ, the membrane-bound G-protein coupled estrogen receptor (GPER) mediates both the genomic and non-genomic effects of estrogen and has been implicated in the development of other tumors such as breast cancer. Interestingly, GPER stimulation activates YAP and TAZ as key effectors of the Hippo pathway. Insulin-like growth factor-1(IGF-1) has also been shown to regulate GPER expression and function, suggesting a crosstalk between growth factors and ERs The availability of translatable preclinical models of human EHE, able to properly recapitulate tumor biology and response to treatment of the clinical tumors, appears instrumental for the development of innovative and effective treatments. Patient-derived xenograft (PDX) models preserve the original histomorphological and molecular characteristics of the originating clinical tumors. We previously demonstrated the consistency between preclinical data obtained on PDXs of different soft-tissue sarcoma histotypes (solitary fibrous tumor, epithelioid sarcoma and dedifferentiated liposarcoma) and clinical results concerning the activity of several cytotoxic and molecularly targeted drugs, providing novel insight into the antitumor effect of different combinations that was instrumental to design novel clinical trials. MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. Their proven deregulation in several types of human cancer, and the possibility to be reliably detected in both tissue and blood specimens, have prompted the assessment of miRNAs as novel cancer biomarkers21. No information is currently available on miRNA expression and function in EHE.

Identification of Risk Factors, Exposomics and Genetic Susceptibility of Melanoma in Children, Adolescents and Young Adults

By retrieving data from several epidemiological and clinical registries across Europe it is aimed to integrate and maximize efforts in order to create a large dataset that serves for a comprehensive analysis of genetic and environmental factors influencing the etiology of melanoma in CAYA. The data will be combined with exposome information about climate and pollution for the development of a weighted risk score. Furthermore, germline high risk mutations and germline low-medium risk variants will be analyzed. Genome and transcriptome sequencing of blood and in selected cases tumour will provide the most comprehensive data to create a polygenic risk score for CAYA melanoma. Transcriptome data will help to identify and characterize the effect of variants of unknown significance in coding, intronic as well as regulatory regions. Tumour sequencing can provide additional information on functional relevance of variants, e.g. secondary hits in tumour tissue or second hits in tumour suppressor genes. Such identification will be highly advantageous to design prevention strategies for melanoma development in CAYA.

Speech and Language Interventions for Italian People With PPA

A total of 30 PPA patients will be recruited, with a clinical and imaging-supported diagnosis of PPA according to the current diagnostic criteria, and MMSE>15. At the study entry (T0), all patients will undergo a clinical interview, a neurological and neuropsychological evaluation, and a speech and language assessment. All these visits will be repeated soon after the intervention (at week 5, W5), at 3 months (M3), and at 6 months (M6) post-intervention. Specifically, measures of patient's and caregivers' satisfaction and patients' functional communication abilities will be collected as primary outcomes. At baseline (T0) and after intervention (W5), all patients recruited at IRCCS San Raffaele and 40% of patients recruited at IRCCS Maugeri Clinical and Scientific Institute will also perform a brain structural and functional MRI. Thirty healthy controls, matched with PPA cases for age and sex, will be also recruited. Only at baseline (T0), all controls will undergo the same visits as the PPA patients, as well as the brain MRI scan. IRCCS Maugeri Clinical and Scientific Institute will be specifically in charge of the development of the SLT protocols, for the online administration of tailored speech and language interventions and for data analysis. IRCCS Ospedale San Raffaele Milano will be specifically in charge of brain structural and functional MRI acquisition, the definition of task-based functional MRI paradigms, and MRI analysis. This unit will also recruit and collect data on the entire sample of healthy controls. Brain structural and functional changes associated with SLT interventions using the most advanced MRI techniques will be investigated. The sociodemographic, clinical, language, speech, and MRI features obtained in patients will be processed through machine learning to develop a computation paradigm that better defines their prediction value for the intervention's efficacy.

Cognitive Control During Sleep: the Strange Case of Self-Awakening

Sleep is often mistakenly conceived as a passive state; however, it actually plays a fundamental role in regulating daytime cognitive functions such as memory and emotion (Klinzing et al., 2019). Additionally, other phenomena suggest that complex cognitive processing may be active during sleep. For example, lucid dreaming, the ability to be aware of dreaming while in the dream, involves a form of volitional control during sleep (Baird et al., 2019). Another scarcely studied experience related to regained cognitive activity during sleep is self-awakening. People habitually use alarms to wake up at a specific time in the morning. Interestingly, some individuals report the ability to wake up without the aid of any timekeeper; we refer to this phenomenon as self-awakening. Although the experience is commonly reported, certain specifics are needed to identify and understand the phenomenon. Firstly, awakening from sleep can be induced by external stimuli but may also occur spontaneously. Secondly, spontaneous awakening can be divided into natural awakening, caused by a "natural" cessation of sleep due to the dissipation of physiological sleep pressure, or self-awakening, driven by the intent to wake up. Thirdly, self-awakening itself requires clarification: it may be habitual (i.e., a person wakes up at the same time every day), in which case circadian rhythms are the driving factor, or it can be induced by will. This latter phenomenon is the primary focus of interest here. Studying self-awakening is not only fascinating but could also provide insights into the presence of specific cognitive processes even at minimal or absent levels of consciousness. There are at least three cognitive operations that a sleeping person must successfully perform to awaken at the intended time. First, they must encode and remember the target time, which should be easily accessible; second, elapsed time during sleep should be constantly estimated and compared to the target time; third, one must regain voluntary control during sleep to awaken. All these operations must be carried out while the sleeping subject is in a state typically characterized by minimal levels of consciousness (Tononi & Massimini, 2008). The experimental model of self-awakening highlights several important issues, particularly the lack of a reliable model for estimating the time interval, from minutes to hours, that passes between falling asleep at night and the moment of self-awakening. This may be explained by limited knowledge of ultradian brain oscillators (i.e., biorhythms with periods shorter than 24 hours) related to the perception of time during nighttime sleep, although the processes involved in the internal timing of circadian rhythms have been extensively studied. These are biologically regulated by a relatively small group of around 10,000 neurons in the suprachiasmatic nucleus of the hypothalamus, oscillating with a 24-hour rhythm. Little is known about ultradian timekeepers of sleep, especially related to the REM (Rapid Eye Movement) sleep cycle, but they likely play a crucial role in self-awakening. So far, self-awakening has been studied using various subjective and objective methodologies, including questionnaires, sleep diaries, actigraphy, and polysomnography. However, no study has integrated all these different approaches Objective The primary aim of this project will be to investigate the psychophysiological and neuropsychophysiological characteristics underlying the phenomenon of self-awakening, introducing an innovative multimodal approach by combining three main methodologies (ecological assessment, neuropsychological approach, and polysomnographic recording). Specifically, the first part of the study will aim to confirm, through an actigraphic survey, that subjects who report this ability at a subjective level (evaluated via the SAQ questionnaire) are indeed capable of performing it. Secondly, the polysomnographic study will aim to evaluate the EEG characteristics of 'self-awakeners' in the 30 minutes preceding self-awakening, compared to those preceding forced awakening caused by an external stimulus. Finally, the neuropsychological assessment will aim to evaluate differences in the cognitive control domains and temporal estimation abilities in 'self-awakeners' compared to subjects unable to self-awaken. The hypothesis is that subjects capable of self-awakening will exhibit distinctive neurophysiological and neuropsychological characteristics. In particular, these subjects are expected to show a reduction in the density and power of slow waves starting 30 minutes before self-awakening, thus indicating the ability to inhibit deep sleep in preparation for wakefulness. Additionally, it is hypothesized that these subjects may exhibit better performance in neuropsychological variables related to cognitive control and temporal estimation.

TeleNEURO-Rehabilitation Systems for Neurodegenerative Conditions: the FIT4TeleNEURO Pragmatic Trial