Lineage-Specific Genome Architecture Links Enhancers and Non-coding Disease Variants to Target Gene Promoters.

Long-range interactions between regulatory elements and gene promoters play key roles in transcriptional regulation. The vast majority of interactions are uncharted, constituting a major missing link in understanding genome control. Here, we use promoter capture Hi-C to identify interacting regions of 31,253 promoters in 17 human primary hematopoietic cell types. We show that promoter interactions are highly cell type specific and enriched for links between active promoters and epigenetically marked enhancers. Promoter interactomes reflect lineage relationships of the hematopoietic tree, consistent with dynamic remodeling of nuclear architecture during differentiation. Interacting regions are enriched in genetic variants linked with altered expression of genes they contact, highlighting their functional role. We exploit this rich resource to connect non-coding disease variants to putative target promoters, prioritizing thousands of disease-candidate genes and implicating disease pathways. Our results demonstrate the power of primary cell promoter interactomes to reveal insights into genomic regulatory mechanisms underlying common diseases.

The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

Many common variants have been associated with hematological traits, but identification of causal genes and pathways has proven challenging. We performed a genome-wide association analysis in the UK Biobank and INTERVAL studies, testing 29.5 million genetic variants for association with 36 red cell, white cell, and platelet properties in 173,480 European-ancestry participants. This effort yielded hundreds of low frequency (<5%) and rare (<1%) variants with a strong impact on blood cell phenotypes. Our data highlight general properties of the allelic architecture of complex traits, including the proportion of the heritable component of each blood trait explained by the polygenic signal across different genome regulatory domains. Finally, through Mendelian randomization, we provide evidence of shared genetic pathways linking blood cell indices with complex pathologies, including autoimmune diseases, schizophrenia, and coronary heart disease and evidence suggesting previously reported population associations between blood cell indices and cardiovascular disease may be non-causal.

Core-curriculum in psycho-oncology: Towards the certification of the psycho-oncologist profession.

BACKGROUND: Issues relating to certification of the Psycho-oncology profession require clarification in order to provide high quality comprehensive psychosocial care within oncology. We conducted a survey identifying existing training, professional registration requirements and accreditation programs, at national levels, for the specialty of psycho-oncology as well as the mandatory presence of this specialist in cancer teams. METHODS: This survey was conducted within the International Psycho-Oncology Society Federation of psycho-oncology societies and included representatives of each national federated society and some countries not belonging to the Federation. Survey questions were emailed requesting specific details, from the registered contact person, for each country, about psycho-oncology training, professional registration and accreditation. RESULTS: Of 43 countries contacted (34 Federated and 9 non-federated members), 39 replied and answered the questionnaire (90, 7%). Disparities were reported between countries, with details indicating differences from having no national program, to quite detailed and legally accredited requirements. The majority of countries had no formally recognized profession of "Psycho-oncologist," while some countries reported that it is mandatory (or recommended to have) a specialist in psycho-oncology in cancer centers and, thus, that an accredited, nationally recognized and certified training in this specialty exists. CONCLUSIONS: The study underlines the need to create a curriculum for the specialty (certification and accreditation) for the profession of psycho-oncology. Given the lack of internationally recognized core standards, ideas and proposals for minimum standards of good care and the training required to deliver this, are explored to clarify who may use the designation "Clinical Psycho-oncologist."

Dignity in Medicine: Definition, Assessment and Therapy.

PURPOSE OF REVIEW: Over the last 20 years, dignity and dignity-conserving care have become the center of investigation, in many areas of medicine, including palliative care, oncology, neurology, geriatrics, and psychiatry. We summarized peer-reviewed literature and examined the definition, conceptualization of dignity, potential problems, and suggested interventions. RECENT FINDINGS: We performed a review utilizing several databases, including the most relevant studies in full journal articles, investigating the problems of dignity in medicine. It emerged that dignity is a multifactorial construct and that dignity-preserving care should be at the center of the health organization. Dignity should be also regularly assessed through the tools currently available in clinical practice. Among dignity intervention, besides dignity models of care, dignity intervention, such as dignity therapy (DT), life review and reminiscence therapy, have a role in maintaining both the extrinsic (preserved when health care professionals treat the patient with respect, meeting physical and emotional needs, honors the patient's wishes, and makes attempts to maintain privacy and confidentiality) and intrinsic dignity (preserved when the patient has appropriate self-esteem, is able to exercise autonomy and has a sense of hope and meaning). Unified trends across diverse medical contexts highlight the need for a holistic, patient-centered approach in healthcare settings. Challenges compromising dignity are pervasive, underscoring the importance of interventions and systematic efforts to address these issues. Future research and interventions should prioritize the multifaceted nature of dignity, striving to create healthcare environments that foster compassion, respect, and dignity across all medical settings.

The pleural gradient does not reflect the superimposed pressure in patients with class III obesity.

BACKGROUND: The superimposed pressure is the primary determinant of the pleural pressure gradient. Obesity is associated with elevated end-expiratory esophageal pressure, regardless of lung disease severity, and the superimposed pressure might not be the only determinant of the pleural pressure gradient. The study aims to measure partitioned respiratory mechanics and superimposed pressure in a cohort of patients admitted to the ICU with and without class III obesity (BMI ≥ 40 kg/m2), and to quantify the amount of thoracic adipose tissue and muscle through advanced imaging techniques. METHODS: This is a single-center observational study including ICU-admitted patients with acute respiratory failure who underwent a chest computed tomography scan within three days before/after esophageal manometry. The superimposed pressure was calculated from lung density and height of the largest axial lung slice. Automated deep-learning pipelines segmented lung parenchyma and quantified thoracic adipose tissue and skeletal muscle. RESULTS: N = 18 participants (50% female, age 60 [30-66] years), with 9 having BMI < 30 and 9  ≥ 40 kg/m2. Groups showed no significant differences in age, sex, clinical severity scores, or mortality. Patients with BMI ≥ 40 exhibited higher esophageal pressure (15.8 ± 2.6 vs. 8.3 ± 4.9 cmH2O, p = 0.001), higher pleural pressure gradient (11.1 ± 4.5 vs. 6.3 ± 4.9 cmH2O, p = 0.04), while superimposed pressure did not differ (6.8 ± 1.1 vs. 6.5 ± 1.5 cmH2O, p = 0.59). Subcutaneous and intrathoracic adipose tissue were significantly higher in subjects with BMI ≥ 40 and correlated positively with esophageal pressure and pleural pressure gradient (p < 0.05). Muscle areas did not differ between groups. CONCLUSIONS: In patients with class III obesity, the superimposed pressure does not approximate the pleural pressure gradient, which is higher than in patients with lower BMI. The quantity and distribution of subcutaneous and intrathoracic adiposity also contribute to increased pleural pressure gradients in individuals with BMI ≥ 40. This study introduces a novel physiological concept that provides a solid rationale for tailoring mechanical ventilation in patients with high BMI, where specific guidelines recommendations are lacking.

Sex differences in schizophrenia-spectrum diagnoses: results from a 30-year health record registry.

This study investigated sociodemographic and clinical differences between the sexes in individuals affected by schizophrenia-spectrum disorders (SSD) who accessed outpatient mental health services. Within a retrospective cohort of 45,361 outpatients receiving care in Ferrara (Italy) from 1991 to 2021, those with a SSD diagnosis were compared between the sexes for sociodemographic and clinical characteristics before and after the index date (when the ICD-9: 295.*diagnosis was first recorded) to assess early trajectory, age and type of diagnosis, and severity of illness indicated by medication use, hospitalization, and duration of psychiatric care. Predictors of discharge were also investigated. Among 2439 patients, 1191 were women (48.8%). Compared to men, women were significantly older at first visit (43.7 vs. 36.8 years) and at index date (47.8 vs. 40.6) with peak frequency at age 48 (vs. 30). The most frequent last diagnosis recorded before the index date was delusional disorder (27.7%) or personality disorder (24.3%) in men and depression (24%) and delusional disorder (30.1%) in women. After the index date, long-acting antipsychotics and clozapine were more frequently prescribed to men (46.5% vs. 36.3%; 13.2% vs. 9.4%, p < 0.05) and mood stabilizers and antidepressants to women (24.3% vs. 21.1%; 50.1% vs. 35.5%; p < 0.05). Women had fewer involuntary admissions (10.1% vs. 13.6%) and were more likely to be discharged as the time under care increased (p = 0.009). After adjusting for covariates, sex was not a significant predictor of discharge. Our study confirmed that sex differences exist in clinical and sociodemographic characteristics of outpatients with SSD and that gender considerations might influence the rapidity of diagnosis and medications prescribed. These findings highlight the need to implement a women-tailored approach in specialist care programs for psychoses.

GEOexplorer: a webserver for gene expression analysis and visualisation.

Gene Expression Omnibus (GEO) is a database repository hosting a substantial proportion of publicly available high throughput gene expression data. Gene expression analysis is a powerful tool to gain insight into the mechanisms and processes underlying the biological and phenotypic differences between sample groups. Despite the wide availability of gene expression datasets, their access, analysis, and integration are not trivial and require specific expertise and programming proficiency. We developed the GEOexplorer webserver to allow scientists to access, integrate and analyse gene expression datasets without requiring programming proficiency. Via its user-friendly graphic interface, users can easily apply GEOexplorer to perform interactive and reproducible gene expression analysis of microarray and RNA-seq datasets, while producing a wealth of interactive visualisations to facilitate data exploration and interpretation, and generating a range of publication ready figures. The webserver allows users to search and retrieve datasets from GEO as well as to upload user-generated data and combine and harmonise two datasets to perform joint analyses. GEOexplorer, available at https://geoexplorer.rosalind.kcl.ac.uk, provides a solution for performing interactive and reproducible analyses of microarray and RNA-seq gene expression data, empowering life scientists to perform exploratory data analysis and differential gene expression analysis on-the-fly without informatics proficiency.

A tale of two constructs: combined assessment of demoralization and subjective incompetence.

Demoralization comprises multiple dimensions. Among them, Subjective Incompetence (SI) is the perception of being incapable of appropriate action in demanding circumstances. SI may be an early sign of demoralization preceding hopelessness, thus we aimed at integrating items related to Subjective Incompetence into the clinical assessment of demoralization. We assessed 414 subjects from the general population with the Demoralization Scale, 24 items (DS24) and the Subjective Incompetence Scale, 12 items (SIS12). We used multiple approaches to detect the optimal number of factors and their item structure, then conducted Bayesian Item Response Theory analyses to study item psychometric properties. Item Response Theory models were used to extrapolate latent severity ratings of clinical dimensions. We modelled the DS24 with five factors (Disheartenment, Sense of Failure, Helplessness, Irritability, Loss of Purpose) and the SIS12 with three (Subjective Incompetence, Inability to plan, Inability to Deal). The more complex IRT model had the best predictive value and helped to identify the items with better discrimination properties across the different dimensions. Twenty items were retained and used to develop the combined Demoralization and Subjective Incompetence Scale (DSIS20), which maintained high correlation with raw and latent trait scores of the longer versions. We combined selected items of the DS24 and the SIS12 to develop the DSIS20, a shorter assessment instrument that includes Subjective Incompetence as well as other clinical dimensions of demoralization. Further study may clarify if DSIS20 may be helpful for the early detection of demoralization.

Effects of electroconvulsive therapy on cortical thickness in depression: a systematic review.

OBJECTIVE: Electroconvulsive therapy (ECT) is one of the most studied and validated available treatments for severe or treatment-resistant depression. However, little is known about the neural mechanisms underlying ECT. This systematic review aims to critically review all structural magnetic resonance imaging studies investigating longitudinal cortical thickness (CT) changes after ECT in patients with unipolar or bipolar depression. METHODS: We performed a search on PubMed, Medline, and Embase to identify all available studies published before April 20, 2023. A total of 10 studies were included. RESULTS: The investigations showed widespread increases in CT after ECT in depressed patients, involving mainly the temporal, insular, and frontal regions. In five studies, CT increases in a non-overlapping set of brain areas correlated with the clinical efficacy of ECT. The small sample size, heterogeneity in terms of populations, comorbidities, and ECT protocols, and the lack of a control group in some investigations limit the generalisability of the results. CONCLUSIONS: Our findings support the idea that ECT can increase CT in patients with unipolar and bipolar depression. It remains unclear whether these changes are related to the clinical response. Future larger studies with longer follow-up are warranted to thoroughly address the potential role of CT as a biomarker of clinical response after ECT.

Depressive symptom complexes of community-dwelling older adults: a latent network model.

Late-life depression has multiple, heterogeneous clinical presentations. The aim of the study was to identify higher-order homogeneous clinical features (symptom complexes), while accounting for their potential causal interactions within the network approach to psychopathology. We analyzed cross-sectional data from community-dwelling adults aged 65-85 years recruited by the European MentDis_ICF65+ study (n = 2623, mean age 74, 49% females). The severity of 33 depressive symptoms was derived from the age-adapted Composite International Diagnostic Interview. Symptom complexes were identified using multiple detection algorithms for symptom networks, and their fit to data was assessed with latent network models (LNMs) in exploratory and confirmatory analyses. Sensitivity analyses included the Partial Correlation Likelihood Test (PCLT) to investigate the data-generating structure. Depressive symptoms were organized by the Walktrap algorithm into eight symptom complexes, namely sadness/hopelessness, anhedonia/lack of energy, anxiety/irritability, self-reproach, disturbed sleep, agitation/increased appetite, concentration/decision making, and thoughts of death. An LNM adequately fit the distribution of individual symptoms' data in the population. The model suggested the presence of reciprocal interactions between the symptom complexes of sadness and anxiety, concentration and self-reproach and between self-reproach and thoughts of death. Results of the PCLT confirmed that symptom complex data were more likely generated by a network, rather than a latent-variable structure. In conclusion, late-life depressive symptoms are organized into eight interacting symptom complexes. Identification of the symptom complexes of late-life depression may streamline clinical assessment, provide targets for personalization of treatment, and aid the search for biomarkers and for predictors of outcomes of late-life depression.

Poor sleep quality may contribute to dysfunctional illness perception, physical and emotional distress in hospitalised patients: results of a national survey of the Italian Society of Consultation-Liaison Psychiatry.

Distress associated with physical illness is a well-known risk factor for adverse illness course in general hospitals. Understanding the factors contributing to it should be a priority and among them dysfunctional illness perception and poor sleep quality may contribute to it. As poor sleep quality is recognised as a major risk factor for health problems, we aimed to study its association with illness perception and levels of distress during hospitalisation. This cross-sectional study included a consecutive series of 409 individuals who were hospitalised in medical and surgical units of different hospitals located throughout the Italian national territory and required an assessment for psychopathological conditions. Sleep quality was assessed with the Pittsburgh (Sleep Quality Index), emotional and physical distress with the Edmonton Symptom Assessment System (ESAS), and illness perception with the Brief Illness Perception Questionnaire (BIPQ). Differences between groups, correlations and mediations analyses were computed. Patients with poor sleep quality were more frequently females, with psychiatric comorbidity, with higher scores in the ESAS and BIPQ. Poor sleep quality was related to dysfunctional illness perception, and to both emotional and physical distress. In particular, by affecting cognitive components of illness perception, poor sleep quality may, directly and indirectly, predict high levels of distress during hospitalisation. Poor sleep quality may affect >70% of hospitalised patients and may favour dysfunctional illness perception and emotional/physical distress.Assessing and treating sleep problems in hospitalised patients should be included in the routine of hospitalised patients.

Cancer mortality in Common Mental Disorders: A 10-year retrospective cohort study.

PURPOSE: Individuals with Common Mental Disorders (CMDs) may have a higher cancer mortality. The purpose of this study was to examine cancer-related mortality among patients with CMDs and verify which cancer types are predominantly involved. METHODS: We used the Regional Mental Health Registry of the Emilia-Romagna region, in Northern Italy to identify patients aged ≥ 18 years who received an ICD 9-CM diagnosis of CMDs (i.e., depressive and neurotic disorders) over a 10 year period (2008-2017). Information on cause of death was retrieved from the Regional Cause of Death Registry. Comparisons were made with data from the regional population without CMDs. RESULTS: Among 101,487 patients suffering from CMDs (55.7% depression; 44.3% neurotic disorders), 3,087 (37.8%) died from neoplasms. The total standardized mortality ratio (SMR) was 1.82 (95% CI 1.78-1.86) while the SMR for all neoplasms was 2.08 (95% CI 2.01-2.16). Individuals of both genders, with both depressive and neurotic disorders had a higher risk of death from almost all cancers compared with the regional population. CONCLUSION: Patients with CMDs have considerably higher cancer mortality risk than the general population. Higher mortality was observed for a broad range of cancers associated with different aetiologies. It is imperative to promote cancer awareness, prevention and treatment for people with CMDs.

The Risk and The Course of Cancer Among People with Severe Mental Illness.

The paucity of data regarding patients with Serious Mental Illness (SMI) and cancer is alarming given the fact that people with SMI, especially schizophrenia, bipolar disorders and severe depressive disorders, have in general poorer access to physical health care and higher morbidity and mortality because of physical illnesses. The aims of this review were to examine the current evidence from existing literature on the risk of developing cancer and its course among people with SMI. Equivocal results emerge regarding the risk of developing some kind of cancer among people with SMI, with contrasting data on a possible higher, similar or lower risk in comparison with the general population. In contrast, a series of studies have pointed out that patients with SMI who develop cancer are less likely to receive standard levels of cancer care, both in terms of screening, diagnosis and treatment. Also, the mortality for cancer has been confirmed to be higher than the general population. A global sensitization about these problems is mandatory in an era in which community psychiatry has been developed in all countries and that policies of prevention, treatment, follow up, and palliative care should regard all the segments of the population, including people with SMI, through an interdisciplinary approach.

DetectIS: a pipeline to rapidly detect exogenous DNA integration sites using DNA or RNA paired-end sequencing data.

MOTIVATION: Recombinant DNA technology is widely used for different applications in biology, medicine and bio-technology. Viral transduction and plasmid transfection are among the most frequently used techniques to generate recombinant cell lines. Many of these methods result in the random integration of the plasmid into the host genome. Rapid identification of the integration sites is highly desirable in order to characterize these engineered cell lines. RESULTS: We developed detectIS: a pipeline specifically designed to identify genomic integration sites of exogenous DNA, either a plasmid containing one or more transgenes or a virus. The pipeline is based on a Nextflow workflow combined with a Singularity image containing all the necessary software, ensuring high reproducibility and scalability of the analysis. We tested it on simulated datasets and RNA-seq data from a human sample infected with Hepatitis B virus. Comparisons with other state of the art tools show that our method can identify the integration site in different recombinant cell lines, with accurate results, lower computational demand and shorter execution times. AVAILABILITY AND IMPLEMENTATION: The Nextflow workflow, the Singularity image and a test dataset are available at https://github.com/AstraZeneca/detectIS. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Novel manifestations of immune dysregulation and granule defects in gray platelet syndrome.

Gray platelet syndrome (GPS) is a rare recessive disorder caused by biallelic variants in NBEAL2 and characterized by bleeding symptoms, the absence of platelet α-granules, splenomegaly, and bone marrow (BM) fibrosis. Due to the rarity of GPS, it has been difficult to fully understand the pathogenic processes that lead to these clinical sequelae. To discern the spectrum of pathologic features, we performed a detailed clinical genotypic and phenotypic study of 47 patients with GPS and identified 32 new etiologic variants in NBEAL2. The GPS patient cohort exhibited known phenotypes, including macrothrombocytopenia, BM fibrosis, megakaryocyte emperipolesis of neutrophils, splenomegaly, and elevated serum vitamin B12 levels. Novel clinical phenotypes were also observed, including reduced leukocyte counts and increased presence of autoimmune disease and positive autoantibodies. There were widespread differences in the transcriptome and proteome of GPS platelets, neutrophils, monocytes, and CD4 lymphocytes. Proteins less abundant in these cells were enriched for constituents of granules, supporting a role for Nbeal2 in the function of these organelles across a wide range of blood cells. Proteomic analysis of GPS plasma showed increased levels of proteins associated with inflammation and immune response. One-quarter of plasma proteins increased in GPS are known to be synthesized outside of hematopoietic cells, predominantly in the liver. In summary, our data show that, in addition to the well-described platelet defects in GPS, there are immune defects. The abnormal immune cells may be the drivers of systemic abnormalities such as autoimmune disease.

Insomnia and circadian sleep disorders in ovarian cancer: Evaluation and management of underestimated modifiable factors potentially contributing to morbidity.

Ovarian cancer is the leading cause of gynaecological cancer deaths and the seventh most commonly diagnosed cancer among women worldwide, so that, as it is related to substantial and increasing disease burden, the management of ovarian cancer survivors should be a priority. Such issues involve prevention and management of emotional distress, anxiety/depressive symptoms, and maintenance of quality of life from initial diagnosis to post-treatment. Within this framework, sleep disturbances, in particular insomnia, are emerging as modifiable determinants of mental health, also contributing to substantial morbidity among cancer, including ovarian cancer. To this aim we conducted a systematic review according to PRISMA guidelines on prevalence and management of insomnia and circadian sleep disorders in ovarian cancer, while selecting 22 papers. Insomnia was evaluated in ovarian cancer and, while circadian sleep disturbances were poorly assessed in ovarian cancer, insomnia increased from 14% to 60% of patients. Insomnia was associated with cancer-related comorbid conditions such as emotional distress, anxiety/depressive symptoms and low quality of life. Despite this evidence, no studies have been conducted about insomnia treatment in ovarian cancer. The burden of insomnia and circadian sleep disorders in patients with ovarian cancer still needs to be addressed, and requires a call to action for the evaluation and management of these potential modifiable factors that might contribute to ovarian cancer morbidity.

A comparison of Dignity Therapy narratives among people with severe mental illness and people with cancer.

OBJECTIVE: To examine Dignity Therapy (DT) narratives in patients with severe mental illness (SMI) and a control group of cancer patients. METHODS: 12 patients with SMI (schizophrenia, bipolar disorders, sever personality disorders) and 12 patients with non-advanced cancer individually participated to DT interviews. DT was tape-recorded, transcribed verbatim and shaped into a narrative through a preliminary editing process. A session was dedicated to the final editing process along with the participant, with a final written legacy (generativity document) provided to the participant. Interpretative Phenomenological Analysis was used to qualitatively analyze the generativity documents. RESULTS: Patients with SMI and patients with cancer presented similar main narrative categories relative to dignity, such as "Meaning making", "Resources", "Legacy", "Dignity"; in addition, inpatients with SMI "Stigma" and inpatients with cancer "Injustice" emerged as separate categories. Patients in both groups strongly appreciated DT as an opportunity to reflect on their life story and legacy. CONCLUSIONS: The study showed that DT is a valuable intervention for people with SMI, grounded in a practical, person-centered approach. All patients found DT as an opportunity to describe their past and present, highlighting changes in the way they relate to themselves and others. These results can guide implementation of DT in mental health settings for people with SMI, as it is for people with cancer.

Violence Against Physicians in the Workplace: Trends, Causes, Consequences, and Strategies for Intervention.

PURPOSE: Violence against healthcare professionals has become an emergency in many countries. Literature in this area has mainly focused on nurses while there are less studies on physicians, whose alterations in mental health and burnout have been linked to higher rates of medical errors and poorer quality of care. We summarized peer-reviewed literature and examined the epidemiology, main causes, consequences, and areas of intervention associated with workplace violence perpetrated against physicians. RECENT FINDINGS: We performed a review utilizing several databases, by including the most relevant studies in full journal articles investigating the problem. Workplace violence against doctors is a widespread phenomenon, present all over the world and related to a number of variables, including individual, socio-cultural, and contextual variables. During the COVID-19 pandemic, incidence of violence has increased. Data also show the possible consequences in physicians' deterioration of quality of life, burnout, and traumatic stress which are linked to physical and mental health problems, which, in a domino effect, fall on patients' quality of care. Violence against doctors is an urgent global problem with consequences on an individual and societal level. This review highlights the need to undertake initiatives aimed at enhancing understanding, prevention, and management of workplace violence in healthcare settings.

Machine Learning and Non-Affective Psychosis: Identification, Differential Diagnosis, and Treatment.

PURPOSE OF REVIEW: This review will cover the most relevant findings on the use of machine learning (ML) techniques in the field of non-affective psychosis, by summarizing the studies published in the last three years focusing on illness detection and treatment. RECENT FINDINGS: Multiple ML tools that include mostly supervised approaches such as support vector machine, gradient boosting, and random forest showed promising results by applying these algorithms to various sources of data: socio-demographic information, EEG, language, digital content, blood biomarkers, neuroimaging, and electronic health records. However, the overall performance, in the binary classification case, varied from 0.49, which is to be considered very low (i.e., noise), to over 0.90. These results are fully justified by different factors, some of which may be attributable to the preprocessing of the data, the wide variety of the data, and the a-priori setting of hyperparameters. One of the main limitations of the field is the lack of stratification of results based on biological sex, given that psychosis presents differently in men and women; hence, the necessity to tailor identification tools and data analytic strategies. Timely identification and appropriate treatment are key factors in reducing the consequences of psychotic disorders. In recent years, the emergence of new analytical tools based on artificial intelligence such as supervised ML approaches showed promises as a potential breakthrough in this field. However, ML applications in everyday practice are still in its infancy.

Debating Euthanasia and Physician-Assisted Death in People with Psychiatric Disorders.

PURPOSE OF REVIEW: Over the last 30 years, medical assistance in dying (MAiD) including euthanasia (EU) and physician-assisted death (or suicide, PAS) has become the center of a large debate, particularly when these practices have involved people with psychiatric illness, including resistant depression, schizophrenia, personality, or other severe psychiatric disorders. We performed a review utilizing several databases, and by including the most relevant studies in full journal articles investigating the problem of MAiD in patients with psychiatric disorders but not in physical terminal conditions (non-terminal, MAiD-NT). RECENT FINDINGS: Literature has shown that a small percentage of people with psychiatric disorders died by MAiD-NT in comparison with patients with somatic diseases in terminal clinical conditions (e.g., cancer, AIDS). However, the problem in the field is complex and not solved yet as confirmed by the fact that only a few countries (e.g., the Netherlands, Belgium, Luxemburg) have legalized MAiD-NT for patients with psychiatric disorders, while most have maintained the practices accessible only to people with somatic disease in a terminal phase. Also, how to make objective the criterion of irremediability of a mental disorder; how to balance suicide prevention with assisted suicide; how to avoid the risk of progressively including in requests for MAiD-NT vulnerable segments of the population, such as minors, elderly, or people with dementia, in a productive-oriented society, are some of the critical points to be discussed. The application of MAiD-NT in people with psychiatric disorders should be further explored to prevent end-of-life rights from contradicting the principles of recovery-oriented care.