The polygenic and multifactorial nature of many psychiatric disorders has hampered the personalized medicine approach implementation in clinical practice. However, induced pluripotent stem cell (iPSC) technology has emerged as an innovative tool for patient-specific disease modeling to expand the pathophysiology knowledge and treatment perspectives in the last decade. Current technologies enable adult human somatic cell reprogramming into induced pluripotent stem cells (iPSCs) to generate neural cells and direct neural cell conversion to model organisms that exhibit phenotypes close to human diseases, thereby effectively representing relevant aspects of neuropsychiatric disorders. iPSCs reflect patient pathophysiology and pharmacological responsiveness, particularly when cultured under conditions that recapitulate spatial tissue organization in brain organoids. Recently, the application of iPSCs has been frequently associated with gene editing that targets the disease-causing gene to deepen the illness pathophysiology and conduct drug screening. Moreover, gene editing has provided a unique opportunity to repair the putative causative genetic lesions in patient-derived cells. Here, we review the use of iPSC technology to model and potentially treat neuropsychiatric disorders by illustrating the key studies on a series of mental disorders, including schizophrenia, major depression disorder, bipolar disorder, and autism spectrum disorder. The future perspective will involve the development of organ-on-a-chip platforms that control the microenvironmental conditions to reflect individual pathophysiological by adjusting physiochemical parameters according to personal health data. This strategy could open new ways to build a disease model that considers individual variability and tailors personalized treatments.

Despite many calls to reduce or eliminate the use of mechanical restraint, it is still widely used in many countries. Studies using patient interviews have a very clear message: Patients experience mechanical restraint as the most humiliating intervention. There seems to be a lack of alternatives with violent patients. We developed a method using 30 kg bags, originally designed for fitness purposes, to be attached to a patient's wrist or ankle under 1:1 supervision. The method was tested with 10 experienced nurses and de-escalation trainers. A video was made and presented to six outpatients who had previously experienced mechanical restraint. All participants were interviewed. Transcribed interviews were analysed using qualitative content analysis. All participants approved of the method as a milder and less humiliating alternative to mechanical restraint. Nurses' main concerns were the risk of falls and the use of the bags as a weapon. The latter could be controlled by using an additional bag. Patients were generally positive, especially if there was a history of abuse. The method should be further developed to replace at least part of mechanical restraints. As with all ‘milder means‘, care should be taken to really replace restraint and not to introduce additional coercion.

Mental disorders impact a significant portion of the global population, presenting substantial challenges to healthcare systems due to high hospitalization costs and resource demands. This narrative review explores the economic implications of mental health disorders, focusing on hospitalization costs, the effectiveness of interventions, and the outcomes of recent research. Materials and Methods: A narrative review was conducted, sourcing articles from PubMed and Google Scholar published between 2014 and 2024. The search terms included combinations related to mental illness, costs, hospital care, and mental healthcare interventions. A total of 1,110 articles were initially identified, with 37 studies meeting the inclusion criteria after rigorous screening by two independent researchers. These studies included quantitative and qualitative data covering a range of outcomes such as hospital admission rates, consumer satisfaction, and quality of life. The findings of the present review reveal that mental disorders significantly increase hospitalization costs due to frequent admissions, extended stays, and the need for specialized treatments. Additionally, physical comorbidities in individuals with mental disorders lead to higher healthcare costs and resource use. Integrated care models, early intervention, and preventive strategies show promise in reducing these costs and improving patient outcomes. Conclusions: Our review emphasizes the critical need for integrated healthcare strategies that address both mental and physical health to reduce hospitalization costs and improve outcomes. Effective management of mental health disorders requires comprehensive approaches, including complex outpatient services and preventive care. Future research should focus on standardizing methodologies to provide clearer insights into the economic impact of mental health conditions and guide effective healthcare strategies.

Purpose: Arab Americans are one of the largest ethnic groups in the United States. The mental health of Arab Americans and opinions on mental health, however, remain understudied despite higher rates of mental illness and lower rates of treatment. Unique cultural conceptualizations of mental illness may generate stigma, contributing to disparities in treatment. This study aimed to assess the attitudes and perspectives of Arab Americans regarding mental illness in order to address barriers to treatment. Methods:Using an anonymous bilingual Qualtrics survey, we assessed Arab and non-Arab participants (n = 294; ages 18+) on their conceptualizations of the causes of mental illness and on their stigma towards mental illness and mental health treatments. Comparisons were performed between Arabs and non-Arabs, as well as among Arabs. Results:Compared to non-Arabs, Arabs reported higher average mental illness stigma and were more likely to rate psychiatric medications as addictive and unhelpful. Among Arabs, being Christian, male, and older (>29 years old) were each associated with higher stigma. Arabs were less likely than non-Arabs to believe in a biological explanation for mental illness. Conclusion: Our results demonstrate higher levels of stigma towards mental illness among Arab Americans, especially Christian, male, and older Arabs, potentially related to a weaker belief in a biomedical model for mental illness. These are among the first findings describing mental illness stigma and beliefs about mental health in an Arab American community and may inform future interventions providing culturally competent care to Arab Americans.

Introduction: The aim is to investigate the possibility of altering the delusional perceptions of psychotic patients by exposing them to a cognitively flexible virtual environment. A flexible vir-tual reality (VR) environment could challenge and enhance the ability to adapt to changing situa-tions and generate novel solutions to core psychotic symptoms. Materials and methods: A systematic review was conducted using different combinations of keywords in different databases. This study was conducted using the PRISMA statement. Results: There is a growing literature on the use of VR to manipulate and normalise perceptual distortions in psychosis. Over the last decade, the number of published studies on VR in mental health has increased 14-fold. Conclusions: A cognitive flexibility virtual environment can alter delusional perception by ex-posing the person to different scenarios that require them to question their assumptions, test their hypotheses, and revise their beliefs. Commonly used biosensors measure heart rate, skin con-ductance and body temperature in relation to different emotional states. Recently, there has been a major shift towards the use of neuroimaging techniques to better understand the pathophysiology of mental disorders. This is where the new wave of biosensor-integrated virtual reality (VR) sys-tems comes in.

Arguably the most important parameter in treating cognitive decline associated with Alzheimer’s disease is the length of time in which improvement, if achieved at all, is sustained. However, monotherapies such as donepezil and memantine are associated with a more rapid decline than no treatment in patients over multi-year follow-ups {Kennedy, 2018 #535}. Furthermore, anti-amyloid antibody treatment, which at best simply slows decline, is associated with accelerated cerebral atrophy [2], resulting in earlier dementia-associated brain volumes for those treated at the MCI stage than untreated patients. In contrast, a precision medicine approach, in which the multiple potential drivers of cognitive decline are identified for each patient and then targeted with a personalized protocol (such as ReCODE), has led to documented improvement in patients with cognitive decline [3]; [4]; [5], but long-term follow-up (>5 years) has not been reported previously. Therefore, we report here sustained cognitive improvement, in some cases for over a decade, in patients treated with a precision medicine protocol—something that has not been reported in patients treated with anti-cholinesterase, glutamate receptor inhibitory, anti-amyloid, or other therapeutic methods. These case studies warrant long-term cohort studies to determine how frequently such sustained cognitive improvements occur in patients treated with precision medicine protocols.

Background: The COVID-19 pandemic led to rapid growth in telemental health services and investment in digital mental health technologies. Digital mental health technologies could expand access to mental health care amid increasing provider deficit by providing tools for expedited psychiatric symptom assessment and treatment augmentation. This systematic review explores the recent evidence for the use of scalable digital tools, including virtual reality, neurofeedback training, wearables, mobile apps, digital phenotyping, and machine learning for PTSD symptom assessment, diagnosis, and treatment. Methods: A PubMed search identified studies on digital technologies with current or future potential for scalability (accessible through a small, digital device without the virtual or in-person presence of a mental health care provider)–and PTSD diagnosis, symptom assessment, or symptom treatment as the primary outcome. Thirty-five studies inform this review. Results: Virtual reality exposure therapy is efficacious for combat-related PTSD treatment. Conclusions of studies investigating apps and neurofeedback training are limited by low sample size and methodological heterogeneity. Machine learning models demonstrate capability in detecting PTSD symptoms via passively collected data from smartphones, wearables, and actively collected data from patient speech, writing, and videos, but standardization of data collection and modeling are needed before application to clinical settings. Conclusions: Advancements in scalable digital tools could address barriers in healthcare access and improve patient engagement by providing asynchronous assessment and treatment augmentation. Future research utilizing diverse patient populations in standardized controlled trials is needed to determine evidence-based protocols for implementation.

Astrocytes, the most abundant glial cells in the brain, are an integral part of the synaptic compartment and contribute to synaptic pruning, a key process for refining neural circuits during early postnatal development (PND). Dysregulations in this process are implicated in various neuropsychiatric disorders, including major depressive disorder (MDD). To investigate astrocyte functions in a physiologically relevant context, organotypic brain slice cultures (OBSCs) offer a powerful model, reproducing more closely in vivo conditions than traditional cell cultures and preserving complex brain architecture and interactions. Here, we present OBSCs as an ex vivo culturing method to provide a platform to explore astrocyte-mediated synaptic pruning dynamics in the rat prefrontal cortex (PFC) during PND. Our approach is based on assessing the role of MEGF10, a key protein involved in synaptic pruning, alongside the synaptic markers synaptophysin and PSD95, using Western blotting to analyse the expression levels of these markers in the cortex of developing rat pups. Additionally, we combine immunofluorescence staining with confocal imaging and IMARIS 9.8 software-assisted analysis to investigate the co-localization of the lysosomal marker LAMP1 with synaptic and astrocytic markers to evaluate the precise rate of synaptic engulfment. The methods presented here allow a deeper examination of an astrocyte-mediated synaptic remodelling in healthy and pathophysiological conditions.

Immunofluorescent methods in vitro have been widely used to characterize the distribution and extent of colocalization of molecules located in various intracellular compartments. These are key processes to better understand the role of those molecules in physiological and pathological conditions.In the brain, interactions of astrocytes with neurons are fundamental for the establishment and proper functioning of neuronal circuits. Among these, the phagocytosis of synapses that need to be removed is a process known as synaptic pruning. When this process is dysregulated, it might lead to the development of several brain disorders. Here, we describe the adaptation of a method to characterize the astrocyte-mediated synaptic phagocytosis and evaluate astrocytic (dys)functions in healthy cells and cells derived from an animal model of major depressive disorder (MDD).

Edvard Munch, a founder of Expressionism was pre-occupied with depicting his subjective experience and the most prolific painter of self-portraits since Rembrandt. Based on evidence that faces and self-related images are more salient than other objects it is plausible that self-portraits, in which the subject and object are the same, reflect the artist’s state of mind. Although he suffered from a variety of physical and psychological illness Munch was not diagnosed with any specificity in his lifetime. Posthumous diagnoses include schizophrenia, anxiety, bipolar and other disorders. Recent research has revealed altered visual perception in such patients. The present study empirically analysed three stylistic elements of Munch’s painted self-portraits and portraits: contrast, colour and fractal dimension and his painted productivity, to determine if variations correlate with critical life events and if so whether they indicate states of mind. It found significant increases in contrast and colour brightness and persistent high complexity during critical periods supporting the conclusion that Munch is diagnostically best described as suffering from early onset schizophrenia and comorbid social anxiety disorder.

Many have speculated that events of personal and financial loss in Rembrandt’s life caused depression and that this is revealed by examination of his self-portraits particularly those painted in old age. Some report detecting various physiological diseases associated with aging, including vision impairment, which may have affected his mood and work. Aging and neurodegenerative disease which often accompanies it, are both associated with depression. Recent advances in imaging and computer technology make it possible to empirically examine changes in artistic style which can contribute to understanding artists’ physical and mental health. In the current study changes in contrast, colour and fractal dimension were measured in the entire corpus of Rembrandt’s painted self-portraits and portraits to determine whether changes in style indicate depression or disease. Productivity was also examined as an indirect indicator. Given the high salience attributed to self-images, it also examined whether differences in style could be detected between self-portraits and portraits of related and unrelated others. The results indicate that it is unlikely that Rembrandt suffered from unipolar or bipolar depression, age-related cognitive decline, or neurodegenerative disease. The data are consistent with someone experiencing episodes of low mood consistent with normal grieving and adversity followed by resilient recovery. There is evidence of a gradient in saliency and complexity between self-portraits and related and unrelated portraits, of a less formal style in portraits of related others and of a ‘late’ style identified by leading art historians consistent with macular degeneration. The results are also consistent with an association of aesthetic preference with mid-level fractal values tending towards the Golden Mean long associated with beauty in nature and in art.

Background: We assessed the pertinence of yearly updating the International Working Group on the Diabetic Foot (IWGDF) risk classification in people with diabetes by quantifying the changes in the risk group and its accuracy in identifying those developing an ulcer (DFU) in a primary care setting. Methods: In our retrospective cohort study, we included all people with diabetes with a foot as-sessment registry between January 2016 and December 2018 in the Baixo Alentejo Local Health Unit. Foot-related data was collected at baseline after one and two years. DFU and/or death until December 2019 were registered. The proportion of people changing their risk status each year was calculated. Accuracy measures of the IWGDF classification to predict DFU occurrence at one, two, and three years were calculated. Results: A total of 2097 people were followed for three years, during which 0.1% died, and 12.4% developed a DFU. After two years, 3.6% of the participants had progressed to a higher-risk group. The IWGDF classification presented specificity values superior to 90% and negative predictive values superior to 99%. Conclusion: Foot risk status can be safely updated every two years instead of yearly. The IWGDF classification can accurately identify those not at risk of DFU.

Introduction: Hospitalization in a COVID-19 unit represents a significant source of stress and psychological distress for patients. Our study aims to determine the factors of psychological distress in the therapeutic and psychosocial management of patients hospitalized with a COVID-19 infection. Methods: This cross-sectional study was carried out over 8 months at the COVID-19 zone of the CHU HASSAN II of FES. 99 patients were evaluated within days of diagnosis by psychometric scales of anxiety, depression, and post-traumatic stress. In the course of this follow-up, we found the presence of psychological impacts in these patients, and we tried to find correlating factors between the occurrence of psychiatric disorders and the set of factors related to sociodemographic data, hospitalization course and treatments taken, as well as family support. Results: 35% of patients had scores in favor of post-traumatic stress disorder, 37% of the patients had definite depression and 50% had anxiety. Post-traumatic stress, depression, and anxiety were correlated with sociodemographic factors, hospitalization, treatments received, and length of stay. Conclusion: The prevalence of anxiety-depressive disorders and post-traumatic stress disorder was high in patients with COVID-19, hence the interest in providing psychological and psychosocial care in the emergency department.

Obsessive–compulsive disorder (OCD) is believed to follow a waxing and waning course, often according to environmental stressors. During the COVID-19 pandemic, pre-existing OCD symptoms were reported to increase and to change from checking to washing behaviors, while new-onset symptoms were predominantly of the hoarding type. In the present study, we followed the evolution of OCD symptoms, anxiety, depression, and insight of illness in forty-six OCD patients throughout the pandemic. Clinical measures were collected at four different time points before and during the COVID-19 pandemic in Italy. Within-subject comparisons were used to compare clinical scale scores across time, and correlations were examined between patients' baseline characteristics and changes in clinical scores. We found that all clinical measures increased during the first Italian lockdown, with respect to the pre-pandemic values. Anxiety decreased during the temporary elimination of restriction provisions, whereas severity of OCD symptoms and insight returned to pre-pandemic values during the second mandatory lockdown. These results were observed only in two sub-groups of patients: those taking benzodiazepines and those with shorter illness duration. Our findings suggest the need of additional clinical attention to these specific sub-groups of OCD patients in case of particularly distressing circumstances, while pointing to a possible adaptive role of their OCD symptoms when the environment requires a higher care of hygiene and extraordinary supply of essential resources.

Existing scales assessing family relations are usually quite long. Our aim was to develop and validate the Family Functioning and Cohesion Scale (FFCS), a self-reported short instrument consisting of 14 items. The validation of the FFCS was based on its administration through an online platform to 481 subjects living in 46 different countries around the world. Cronbach's alpha was 0.85 (ranging from 0.83 to 0.86 if any one item was deleted), signifying high internal consistency. The scale can be considered as a sole factor based on its high consistency, while factor analysis produced three factors corresponding to “communication”, “anger/resentment/aggression” and “values and beliefs”. Test-retest reliability correlation coefficient was found to be 0.88 at a 2-week interval. As far as external validity is concerned, the correlation coefficient of the FFCS with the General Functioning subscale of the McMaster Family Assessment Device (FAD) was 0.83. The high measures of consistency, reliability, and validity of the FFCS, combined with its short length, make it an invaluable tool for use in research as well as in any professional dealing with families in the clinical fields of psychiatry, psychology, social work or any other relevant specialty.

In the brain, astrocytes regulate shape and functions of the synaptic and vascular compartments through a variety of released factors and membrane-bound proteins. An imbalanced astrocyte activity can therefore have drastic negative impacts on brain development, leading to the onset of severe pathologies. Clinical and pre-clinical studies show alterations in astrocyte cell number, morphology, molecular makeup and astrocyte-dependent processes in different affected brain regions in neurodevelopmental (ND) and neuropsychiatric (NP) disorders. Astrocytes proliferate, differentiate and mature during the critical period of early postnatal brain development, a time window of elevated glia-dependent regulation of a proper balance between synapse formation/elimination, which is pivotal in refining synaptic connectivity. Therefore, any intrinsic and/or extrinsic factors altering these processes during the critical period may result in an aberrant synaptic remodelling and onset of mental disorders. The peculiar bridging position of astrocytes between synaptic and vascular compartments further allows them to “compute” the brain state and consequently secrete factors in the bloodstream, which may serve as diagnostic biomarkers of distinct healthy or disease conditions.Here, we collect recent advancements regarding astrogenesis and astrocyte-mediated regulation of neuronal network remodelling during early postnatal critical periods of brain development, focusing on synapse elimination. We then propose alternative hypotheses for an involvement of aberrancies in these processes in the onset of ND and NP disorders. In light of the well-known differential prevalence of certain brain disorders between males and females, we also discuss putative sex-dependent influences on these neurodevelopmental events.From a translational perspective, understanding age- and sex-dependent astrocyte-specific molecular and functional changes may help to identify biomarkers of distinct cellular (dys)functions in health and disease, favouring the development of diagnostic tools or the selection of tailored treatment options for male/female patients.

Objective: The influence of gender on the number and pattern of co-morbid psychiatric illness was archivally compared between patients with and without an Alcohol Use Disorder (AUD) among psychiatrically treated individuals drawn from a large Danish birth cohort. Method: By age 45, fifteen percent of the Copenhagen Perinatal Birth Cohort (N=8,109) had been treated in a Danish psychiatric facility. Of those 1,247 patients, 368 were assigned an AUD diagnosis (29.5%). All psychiatric diagnoses assigned to these patients, over all admissions, were classified into one of 14 broad ICD-10 F categories for comparative purposes. Results: More of the patients with an AUD diagnosis were male. Patients with an AUD diagnosis were significantly more likely to receive two or more non-AUD psychiatric diagnoses than patients without an AUD diagnosis. The number of psychiatric diagnoses was greater for female than male AUD patients, a difference not found among male and female patients without an AUD diagnosis. For patients with no AUD diagnosis, the influence of gender on the pattern of psychiatric disorders was similar to that commonly reported. In contrast, the influence of gender on the number and pattern of psychiatric disorders for patients with an AUD diagnosis indicated fewer gender differences. Several diagnostic categories that discriminated male from female patients without an AUD-related diagnosis, no longer discriminated male from female patients with an AUD-related diagnosis. Conclusions: Our findings suggest that gender differences associated with psychiatric comorbidity that have been reported in large heterogenous study, should not be generalized to specific diagnostic groups without further study.

Depression, anxiety, and pain are part of a common phenomenon that requires to be studied together when evaluating patients with chronic pain. The aim of the study was to examine the correlations between depression, anxiety and pain intensity in patients with chronic pain and how they change when a depressive episode was added. A sample of 120 patients with chronic pain (age: 51.90±11.94; 81.7% female; 18.3% male) was studied in two stages with a three-month period between them. Patients with a depressive episode (n=61) were treated with antidepressants and analgesics, while a patient without depression (n=59) was treated only with analgesics. The scales used to achieve the objectives were: HAM-D-17, Spielberger‘s STAI and VAS. Insignificant correlations were found between depression, state and trait anxiety, and pain intensity (p<0,05) in the group without depression, except for a significant one between depression and state anxiety (p<0,01) in the second stage. Significant correlations were identified between all indicators (p<0,01) in the group with depression at the two stages. Those in the second stage were stronger. The interrelations between sensory and affective aspects of pain were stronger when a depressive episode occurs, the severity of which determines their dynamics.

Background/Objectives: Parental internalizing issues, particularly maternal mental health, can significantly influence adolescents' mental health by altering parenting behaviors and roles. This study aims to explore how parental rejection, a dimension of both maternal and paternal behavior, moderates the relationship between parental depression, anxiety, and stress with adolescents' mental health and quality of life. We hypothesized that parental rejection would have a significant moderating effect on these relationships; Methods: This cross-sectional, non-interventional study involved 206 parents (138 mothers) of adolescents aged 12-18 years from the general population. Participants were recruited online via convenience sampling and completed the Depression Anxiety Stress Scale (DASS), the Parental Acceptance-Rejection Questionnaire, the KIDSCREEN-27 to evaluate adolescents' quality of life, and the Strengths and Difficulties Questionnaire to assess adolescents' mental health; Results: Parental rejection was found to moderate the relationship between maternal anxiety and adolescents' quality of life, as well as between maternal anxiety and adolescents' mental health problems. Paternal rejection moderated the relationship between paternal stress and adolescents' mental health. However, parental rejection did not moderate the relationship between parental depression and adolescents' quality of life or mental health; Conclusions: These findings emphasize the significant role of maternal rejection in the association between maternal mental health, particularly anxiety, and adolescents' mental health outcomes. Paternal rejection also showed some moderating effects, though to a lesser extent. These results underscore the importance of considering both maternal and paternal influences in adolescent mental health and quality of life. Further research is necessary to fully understand the gender-specific dynamics of these relationships.

This narrative review provides an in-depth analysis of attachment during adolescence, empha-sizing how early attachment experiences shape emotional, social, and psychological development. Drawing from the foundational work of Bowlby and Ainsworth, it revisits attachment theories and explores how the attachment system evolves as adolescents seek greater autonomy while maintaining bonds with caregivers. The review discusses the prevalence and developmental con-sequences of attachment-related disorders, such as reactive attachment disorder and disinhibited social engagement disorder, particularly in relation to adverse caregiving environments. Key themes include the intergenerational transmission of attachment, where parental reflective func-tioning and early caregiving behaviors influence attachment security across generations. The evolving role of fathers, peer relationships, and romantic bonds in adolescence are explored as significant factors shaping attachment patterns during this developmental period. Methodologi-cal considerations highlight the value of qualitative approaches, including interviews and obser-vational methods, for capturing the complexity of adolescent attachment dynamics. Additionally, the review addresses the processes that contribute to both continuity and change in attachment classifications over time, emphasizing the impact of life events, parental behaviors, and develop-mental transitions. The implications of attachment for developmental psychopathology, particu-larly in relation to emotional regulation and psychosocial functioning, are discussed. Finally, the review calls for further interdisciplinary research to deepen understanding of attachment mecha-nisms, using advanced technologies and culturally sensitive approaches to improve mental health and developmental outcomes across the lifespan.

The editorial explores the realm of emerging translational research in neurology and psychiatry, providing insights into various subjects, including neurodegenerative disorders and innovative therapeutic methods. The main objective is to study neurological and psychiatric disorders, such as Alzheimer's disease, with a particular emphasis on techniques for neural regeneration and repair. The editorial highlights the importance of taking a comprehensive approach to studying and treating complex neurological and psychiatric conditions. This involves thoroughly reviewing research papers on the causes, development, biomarkers, and treatment options for these conditions. The editorial emphasizes the necessity of using multidisciplinary and integrative methods to gain a deeper understanding and improve the treatment of these conditions. The development of an animal model for recurrent primary dysmenorrhea showcases the innovative techniques employed in the investigation of gynecological disorders, illustrating the capacity of translational research to connect fundamental scientific knowledge with practical medical applications. The cooperative endeavors of researchers and clinicians emphasized in this editorial lay the foundation for revolutionary advancements that hold the potential to enhance outcomes for individuals afflicted with neurological and psychiatric disorders globally.

Every year around 800 000 people commit suicide, this represents one death every 40 seconds. In the search for possible biological biomarkers associated with suicide and/or psychiatric disorders, serum cholesterol levels have been extensively explored. Several studies have indicated that cholesterol and associated proteins, especially apolipoproteins (Apos), may play an important role in the diagnosis, prognosis, and susceptibility of suicide. Here, we describe the current knowledge and findings in the relationship between apolipoproteins and suicide.

The art of observing and describing behaviors has driven diagnosis and informed basic science in Psychiatry. In recent times, studies of mental illness are focused on understanding the brain’s neurobiology but there is a paucity of information on the potential contributions from peripheral activity to mental health. In Precision Medicine, this common practice leaves a gap between bodily behaviors and genomics that we here propose to address with a new layer of inquiry that includes genes’ expression on tissues inclusive of brain, heart, muscle-skeletal and organs for vital bodily functions. We interrogate genes’ expression on human tissue as a function of disease-associated genes. By removing genes linked to disease from the typical human set, and recomputing the genes’ expressions on the tissues, we can compare the outcomes across mental illnesses, well-known neurological conditions, and non-neurological ones. We find that major neuropsychiatric conditions that are behaviorally defined today (e.g. Autism, Schizophrenia, Depression) through DSM-observation criteria, have strong convergence with well-known neurological ones (e.g. Ataxias, Parkinson), but less overlap with non-neurological ones. Surprisingly, tissues majorly involved in the central control, coordination, adaptation and learning of movements, emotion and memory are maximally affected in psychiatric diagnoses along with peripheral heart and muscle-skeletal tissues. Our results underscore the importance of considering both the brain-body connection and the contributions of the peripheral nervous systems to mental health.

Post-traumatic stress disorder (PTSD), a mental disorder caused by exposure to traumatic stress, affects 5-10% of the world’s population. PTSD is associated with several medical and neurological comorbidities. It has been suggested that these are due to accelerated aging, and that changes in telomere length (TL) and telomerase enzyme activity may serve as biomarkers of this process. Early research in this field suggested that TL was significantly reduced in PTSD. The current review was conducted to provide a critical analysis of recent clinical and translational research on telomere length and telomerase in PTSD. The results of 26 clinical studies suggest that TL in PTSD is highly variable, and may be influenced by methodological, demographic, trauma-related and psychosocial factors. There is no evidence for altered telomerase activity in PTSD, though this was hypothesized by earlier workers in the field. Translational research suggests that exposure to traumatic stress does lead to TL shortening. Overall, it is likely that TL in PTSD depends on several variables that are specific to individuals and groups. Other markers of cellular aging, such as epigenetic changes, may be more specific indices of accelerated aging in patients with PTSD.

Abstract: Background/Objectives: Schizophrenia (SZ) is a severe psychiatric disorder characterized by a complex interplay of genetic, developmental, and environmental factors that significantly increase the risk of suicidal ideation (SI) and suicide attempts (SAs). This systematic review synthesizes current research on the developmental predictors of SI in individuals with SZ, aiming to delineate the multifactorial etiology of suicide within this population. Methods: A comprehensive search across Medline, PsycINFO, and EMBASE databases identified 23 eligible studies, emphasizing the varied methodological approaches and the global distribution of research efforts. Results: These studies demonstrate a robust association between early life adversities, particularly childhood trauma such as physical neglect, emotional abuse, and sexual abuse, and the increased prevalence of SI and SAs in SZ. This review also highlights the significant genetic factors associated with development of suicidality in SZ, suggesting that polymorphisms in inflammation-related genes and neurodevelopmental abnormalities may influence susceptibility to SI. Notably, family history of psychiatric conditions may exacerbate the risk of SI through both hereditary and environmental mechanisms. Environmental factors, including socioeconomic status and social support, are also implicated, underscoring the role of broader socio-environmental conditions influencing outcomes. Conclusions: This review supports the integration of biopsychosocial models in understanding SI in SZ, advocating for interventions addressing the complex interplay of risk factors and the need for longitudinal studies to elucidate the dynamic interactions between risk factors over time. This comprehensive understanding is crucial for developing targeted preventative strategies and enhancing the clinical management of SZ, aiming to reduce suicidality in this vulnerable population.

Introduction: Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental condition in children in Saudi Arabia based on the results of the national mental health survey. ADHD significantly impacts the child and their family dynamics, particularly causing increased stress and diminished life quality for parents. In Saudi Arabia, there is a research gap regarding the quality of life and coping mechanisms of parents managing children with ADHD. This study assesses levels of depression and anxiety, quality of life, and coping strategies used by parents of children diagnosed with ADHD. Methods: We conducted a cross-sectional online survey with 151 parents of ADHD-diagnosed children, utilizing the WHOQOL-BREF for life quality, the brief-COPE for coping strategies, and the Patient Health Questionnaire (PHQ): depression (PHQ9-9 items) and generalized anxiety (GAD7-7 items) modules. Results: Among the parents surveyed, 36% reported moderate to severe depression, while 39.1% experienced moderate to high anxiety levels. Quality of life positively correlated significantly with higher household monthly income (HHI), employment status, sibling count, and effective coping strategies. Conversely, a parent's age, educational level, and particularly maternal status were inversely related to anxiety levels, with fathers displaying higher maladaptive coping scores. Conclusion: The study sheds light on the considerable anxiety and depression experienced by parents of children with ADHD, significantly affecting their quality of life. Lower parents' quality of life is associated with high levels of depression, anxiety, and ineffective coping strategies. These insights highlight the critical need for interventions to aid parental mental health, thereby improving their overall quality of life amidst ADHD challenges.

Depression is the commonest mental disorder worldwide. Both antidepressants and psychotherapy are effective in treating depression, but response to these treatments is often incomplete. Yoga-based interventions (YBIs) have emerged as a promising adjunctive treatment for depression. Recent research has attempted to identify the biological mechanisms associated with the antidepressant actions of YBIs. In this scoping review, conducted according to the PRISMA-ScR guidelines, the PubMed and Scopus databases were searched to retrieve research on biomarkers of response to YBIs in patients with depression. Eleven studies were included in the review. Based on these studies, YBIs may improve depression through beneficial effects on systemic inflammation, stress axis regulation, cardiac autonomic functioning, and possibly reductions in oxidative stress-related cellular damage. Increases in brain-derived neurotrophic factor (BDNF) may represent a final common pathway upon which these processes converge. Though these results are theoretically plausible, they should be interpreted with caution due to certain methodological limitations in the existing research. Replication of these results and improvements in study methodology, and the evaluation of other biomarkers relevant to the pathophysiology of depression, could further elucidate the mechanism of action of YBIs in this disorder, and identify which patients would benefit most from this treatment approach.

The purposes of this study were to identify clinician’s characteristics associated with higher prescription rates of long-acting injectable (LAI) antipsychotics, as well as the information sources influencing medical decision-making about treatment of schizophrenia. We surveyed 202 psychiatrists during 6 regional French conferences (Bordeaux, Lyon, Marseille, Nice, Paris, Strasbourg). Data on the characteristics of practice, prescription rates of antipsychotic and information sources about their clinical decisions were collected. Most of psychiatrists used second-generation antipsychotic (SGA), and preferentially an oral formulation, in the treatment of schizophrenia. SGA LAI was prescribed to 30.4% of schizophrenic patients. The duration and the type of practice did not influence the class or formulation of antipsychotics used. The clinicians following the higher percentage of schizophrenic patients were associated with the higher use of LAI antipsychotics and the lower use of oral SGA. Personal experience, government regulatory approval and guidelines for the treatment of schizophrenia were the 3 main contributing factors guiding the clinical decision-making of clinicians about treatment of schizophrenia. The more clinicians follow schizophrenic patients, the more they use LAI antipsychotic. The development of specialised programmes with top specialists should lead to better use of LAI in the treatment of schizophrenia.

While the majority of previous studies assessing pain-related variables in psychopaths used electric shocks, little is known about the effectiveness of alternative pain-inducing methods to increase emotional responses such as fear and anxiety. A small sample of healthy undergraduate men (N = 15) was recruited to assess the effectiveness of a heat stimulus to induce pain in an immediate versus delayed punishment paradigm. Although pain catastrophizing, anxiety, and threat of pain did not increase throughout the experiment, participants experienced a significant increase of fear of pain and pain intensity, indicating that the heat stimulus was effective in inducing pain. Furthermore, subjects were slower in initiating the pain stimulus during the first five trials, but no time difference was found during the 15 remaining trials. No correlation was found between psychopathic traits and pain-related variables, with the exception of inconsistent results within the Fearless Dominance factor. Findings are discussed in terms of improvement for a larger scale study involving psychopathic individuals.

Stress is a natural yet potentially harmful aspect of human life, necessitating effective management, particularly during overwhelming experiences. This paper presents a scoping review of personalized stress detection models using wearable technology. Employing the PRISMA-ScR framework for rigorous methodological structuring, we systematically analyzed literature from key databases including Scopus, IEEE Xplore, and PubMed. Our focus was on biosignals, AI methodologies, datasets, wearable devices, and real-world implementation challenges. The review presents an overview of stress and its biological mechanisms, details the methodology for the literature search, and synthesizes the findings. It shows that biosignals, especially EDA and PPG, are frequently utilized for stress detection and demonstrate potential reliability in multimodal settings. Evidence for a trend towards deep learning models was found, although the limited comparison with traditional methods calls for further research. Concerns arise regarding the representativeness of datasets and practical challenges in deploying wearable technologies, which include issues related to data quality and privacy. Future research should aim to develop comprehensive datasets and explore AI techniques that are not only accurate but also computationally efficient and user-centric, thereby closing the gap between theoretical models and practical applications to improve the effectiveness of stress detection systems in real scenarios.

Traditional classroom teaching model can no longer meet the needs of students' ability development. As a new model actively advocated in the modern education concept, personalized teaching focuses on the development needs of students and emphasizes respect for students' individualized growth. In this work, we utilize deep learning method to recommend teaching strategies for different features of students. Specifically, the proposed method includes the construction of a multi-layer neural network model, which can analyze students' multi-dimensional learning data and behavior patterns, so as to recommend the most suitable teaching strategies for individual students. Through data collection and preprocessing, model architecture design, model training and optimization, the model gradually improves the accuracy of prediction and recommendation. Experimental analysis verifies the effectiveness of the model through field teaching experiments, and the results show that the personalized teaching strategy based on deep learning can significantly improve the learning effect and participation of students.

In recent years, the scientific and technological developments led to an explosion of available videos on the web, increasing the necessity of fast and effective video analysis and summarization. Video summarization methods aim to generate a synopsis by selecting the most informative parts of the video content. The user’s personal preferences, often involved in the expected results, should be taken into account in the video summaries. In this paper, we provide the first comprehensive survey on personalized video summarization relevant to the techniques and datasets used. In this context, we classify and review personalized video summary techniques based on the type of personalized summary, on criteria, on the video domain, on the source of information, on the time of summarization, and on the machine learning technique. Depending on the type of methodology used by the personalized video summarization techniques for the summary production process, we classify the techniques into five major categories, which are feature-based video summarization, key frame selection, shot selection-based approach, video summarization using trajectory analysis, and personalized video summarization using clustering. We also compare personalized video summarization methods and present 37 datasets used to evaluate personalized video summarization methods. Finally, we analyze opportunities and challenges in the field and suggest innovative research lines.

Objective biomarkers have been a critical challenge for the field of psychiatry, where diagnostic, prognostic and theranostics assessments are still based on subjective narratives. Psychopathology operates with idiographic knowledge and subjective evaluations incorporated into clinical as-sessment inventories, but is considered to be a medical discipline and, as such, uses medical in-tervention methods (e.g., pharmacological, ECT; rTMS; tDCS), and therefore is supposed to oper-ate with the language and methods of nomothetic networks. The idiographic assessments are pro-visionally “quantified” into “structured clinical scales” to in some way resemble nomothetic measures. Instead of fostering data merging and integration, this approach further encapsulates the clinical psychiatric methods, as all other, biological tests (molecular, neuroimaging) are per-formed separately, only after the clinical assessment has provided diagnosis. Translational cross-validation of clinical assessment instruments and fMRI is an attempt to address the gap. The aim of this approach is to investigate whether there exist common and specific neural circuits, which underpin differential item responses to clinical self-rating scales during fMRI session in pa-tients suffering from the two main spectra of mental disorders: schizophrenia and major depres-sion. The current status of this research program and future implications to promote the devel-opment of psychiatry as a medical discipline are discussed.

Previous studies suggested that trauma-focused cognitive behavior therapy (TF-CBT) is effective in reducing symptoms of post-traumatic stress disorder (PTSD) and depression in children and adolescents. However, the effects of app-assisted TF-CBT-based interventions in psychiatric clinics compared to treatment-as-usual (TAU) are under-explored. The purpose of this study was to reveal the added value of the app-assisted TF-CBT-based intervention as an add-on to TAU. The digitalized measures of the Child and Adolescent Trauma Screen (CATS), The Adolescent Dissociative Experience Scale (A-DES), Short Moods and Feelings Questionnaire (SMFQ), PTSD Checklist (PCL-5), and Children's Post-Traumatic Cognitions Inventory (CPTCI) were applied at baseline and post-treatment. The app-assisted TF-CBT-based group participants started with higher levels of negative alterations in cognition and mood compared to TAU participants but at post-treatment, no significant differences were observed between the app-assisted TF-CBT and TAU groups. Within the app-assisted TF-CBT group, post-treatment scores were significantly lower in post-traumatic stress symptoms, intrusion symptoms, alterations in arousal and reactivity, overall post-traumatic cognitions, and belief in being "a fragile person in a scary world”. Within the TAU group, post-treatment scores were notably lower just in dissociation and intrusion symptoms. The study suggests that app-assisted TF-CBT-based intervention can be effective in addressing specific trauma-related symptoms. The findings imply the necessity for screening for traumatic experiences, incorporating trauma-informed care, implementation of TF-CBT into treatment protocols, utilization of app-assisted interventions, tailoring interventions to individual needs, and comprehensive assessment and monitoring of treatment progress.

Adaptive hyperactivity, characterized by increased activity levels and novelty-seeking traits without mood disorders, is prevalent among older adults in Sardinia's "blue zone," an area with high longevity. This study aims to evaluate the adaptive nature of hyperac-tivity concerning quality of life, social rhythms, and mood symptoms in individuals from this region, particularly among older adults over 80. Methods: This observational cross-sectional study included adults and older adults over 80 years from Sardinia's blue zone, recruited from the dermatology clinic at the University Hospital of Cagliari. Partici-pants underwent psychiatric interviews and completed the Mood Disorder Questionnaire (MDQ), Patient Health Questionnaire (PHQ-9), SF-12, and Brief Social Rhythm Scale (BSRS). Data were compared with national and regional normative data. Results: Older adults in the blue zone demonstrated higher MDQ positivity (22.58%) compared to na-tional averages (0.87%), without corresponding increases in dysregulated rhythms, de-pressive symptoms, or reduced quality of life. Younger elders (65-79 years) showed in-creased rhythm dysregulation (BSRS score: 20.64±7.02) compared to adults (17.40±6.09, p=0.040), but this trend was not observed in older elders (80+ years). No significant differ-ences were found in CH3SH and (CH3)2S levels between groups. Conclusions: Hyperactiv-ity observed in older adults from Sardinia's blue zone appears adaptive, not linked to so-cial rhythm dysregulation, depressive symptoms, or diminished quality of life, suggesting resilience factors that may contribute to longevity. These findings support the potential classification of such hyperactivity as beneficial rather than pathological, warranting fur-ther research into biomarkers and psychoeducational interventions to prevent the onset of bipolar disorders in predisposed individuals.

Recent advances in organoid technology have revolutionized cancer biology and thera-peutic interventions, offering personalized immunotherapy treatment. Organoids, three-dimensional cell cultures derived from patient tumors, accurately replicate the tumor microenvi-ronment, providing unprecedented insights into tumor-immune interactions and therapeutic re-sponses. In this literature-based study, we discuss various culture methods for the diverse appli-cations of organoids in cancer immunotherapy, including drug screening, personalized treatment strategies, and mechanistic studies. Additionally, we address the technological challenges asso-ciated with these methods and propose potential future solutions to accelerate the development of novel immunotherapeutic approaches. This review highlights the transformative potential of or-ganoid models in advancing preclinical cancer immunotherapy modeling, screening, and evalua-tion, paving the way for more effective and personalized cancer treatments.

Despite the clinical significance of partial posttraumatic stress disorder (PTSD), research on its associated cognitive function profiles is notably lacking. This study aimed to identify distinct cognitive function profiles in patients with partial PTSD. Medical records of Vietnamese War Korean Veterans undergoing psychiatric assessments, including the Clinician-Administered PTSD Scale (CAPS) and neurocognitive tests on the same day, were retrospectively reviewed. The participants were divided into partial PTSD (N = 10) and non-PTSD (N = 36) groups based on the CAPS interview. Neurocognitive test score profiles of the partial PTSD and non-PTSD groups were compared. Covariance analysis adjusted for potential confounders in cognitive function. In cognitive profiles, executive function, mental flexibility (measured by Trail Making Test B), and concentration (measured by the Mini-Mental Status Exam) were significantly poorer in the partial PTSD group. When adjusted for age, depressive symptoms, and education level, no significant differences were observed in the cognitive profiles between the partial PTSD and non-PTSD groups. In the current study, executive function and concentration showed deficits in patients with partial PTSD compared with those without PTSD. Partial PTSD cognitive profiles displayed no significant differences from non-PTSD profiles when adjusted for possible confounders such as depressive symptoms.

The genetic causes of the differentiated, highly treatable and mostly non-fatal papillary thyroid cancer (PTC) are not yet fully known. The widely accepted PTC etiology blames altered sequence or/and expression level of certain biomarker genes. However, our previous studies found that the PTC biomarkers played significantly lower roles than the personalized PTC Gene Master Regulators. Our publicly accessible gene expression data from the cancer nodule and the surrounding normal tissue of surgically removed PTC tumor were re-analyzed to determine the transcriptomic effects on the genomic fabrics responsible for the DNA replication, repair and transcription. Tumor results were compared to the gene expression profiles of the papillary (BCPAP) and the anaplastic (8505C) human thyroid cancer cell lines. The analyses were carried out from the Genomic Fabric Paradigm (GFP) perspective that provides the most theoretically possible comprehensive characterization of the transcriptome and its alterations in disease. The study indicated that, in addition to regulating numerous genes, changes in the homeostatic control of transcript abundances and remodeling of the gene networks had major contributions to the PTC occurrence, resilience and proliferation. Therefore, the molecular mechanisms responsible for gene expression control and inter-coordination should also be considered when designing personalized anti-cancer gene therapies.

This paper presents an on-device semi-supervised human activity detection system that can learn and predict human activity patterns in real time. The proposed semi-supervised learning (SSL) framework uses sparsely labelled user activity events acquired from Inertial Measurement Unit (IMU) sensors installed as wearable device. The objective is to learn classification of multiple classes of human activities in real-time. The proposed cluster-based learning model in this approach is trained with data from the same target user, thus preserving data privacy while providing personalized activity detection services. Two different cluster labelling strategies, namely, population-based, and distance-based, are employed to achieve the desired classification performance. A comparative study of these strategies has been presented in terms of classifiability and classification accuracies. The proposed system is shown to be computationally efficient, which is relevant in the context of limited computing resources on typical wearable devices. The trade-off between classification accuracy and computation complexity is analyzed for different algorithmic hyper-parameters and other system parameters. Extensive experimentation and simulation study have been conducted on a multi-user human activity data from the public do-main in order to validate the proposed learning paradigm.

This systematic review provides a comprehensive neuropsychological analysis of psychotic spectrum disorders, including schizophrenia, bipolar disorder, and depression. It explores cognitive impairments in memory, attention, and executive function, and the relation between brain abnormalities and these deficits. The paper emphasizes the use of neuropsychological tests in diagnosis and early psychosis management, while also discussing interventions, the impact of dementia on psychosis, and the neurobiological patterns associated with these conditions. Additionally, it underlines the importance of childhood trauma in the development of psychosis and examines the effects of substance abuse and brain injury. Neuropsychological evaluations and targeted therapies are highlighted as crucial for the understanding, diagnosis, and treatment of psychotic disorders. The research further includes evidence of neurocognitive dysfunction in individuals with a high risk of psychosis and emphasizes the advanced brain aging in schizophrenia and bipolar disorder. The necessity of comprehensive clinical evaluations and targeted therapies for cognitive impairments is underscored throughout the research. The potential effects of dementia on individuals with psychosis, neurobiological patterns, the role of childhood trauma, the impact of psychosis in dementia patients, and proposed treatments are also explored in depth. Overall, the paper underscores the integral role neuropsychological knowledge plays in understanding, diagnosing, managing, and treating psychotic spectrum disorders.

This paper presents an innovative methodology for enhancing museum visitor experiences through personalized content delivery using a combination of explicit and implicit visitor profiling. The approach integrates Bluetooth Low Energy (BLE) smart badges to collect telemetry data, enabling precise visitor localization and dynamic group formation based on real-time proximity and shared interests. Initial profiling begins with OAuth registration and brief surveys, which is then refined through continuous tracking of exhibit interactions and time spent at each exhibit. An AI-driven system delivers content to individual and group profiles, fostering both personalized learning and social interaction. This methodology addresses the limitations of traditional profiling by adapting to visitor behaviors in real-time while maintaining a strong focus on data privacy and ethical considerations. The proposed system not only enhances engagement and satisfaction but also sets the stage for future advancements in personalized cultural experiences.

Anxiety disorders significantly reduce patients' quality of life. Current pharmacological treatments, primarily benzodiazepines and antidepressants, are associated with numerous side effects. Consequently, there is a continual search for alternative methods to traditional therapies that are less burdensome for patients and broaden their therapeutic options. In this review, we examined recent evidence on alternative treatments for anxiety disorders, including physical activity, mindfulness, VR technology, biofeedback, herbal remedies, and transcranial magnetic stimulation (TMS), cryotherapy, hyperbaric therapy, vagus nerve stimulation, MDMA, electroconvulsive therapy (ECT), and eye movement desensitization and reprocessing (EMDR) therapy. Our objective was to determine the role of these selected alternative methods in the treatment of anxiety disorders. Alternative treatments significantly expand the options available to patients and clinicians, with many serving as adjuncts to traditional therapies. Among the methods presented, mindfulness has the most significant therapeutic potential.

In the current era of emerging technologies and cutting-edge inventions, it is equally important to consider the ethical aspects of research and innovations to have an ethical space for the sustainable progress and safety of humanity. The field of nanotechnology research and innovation often faces criticism due to its potential adverse impacts on health, the environment, limited accessibility, high costs, and concerns about data privacy. Therefore, it is crucial to address and resolve these ethical issues systematically. In this regard, we present our findings and methods for exploring the application of the ethics technology assessment method by considering its relevance at different stages of innovation development. Specifically, the present work provides a conceptual framework for ethics technology assessment focused on evaluating a significant innovation in nanotechnology within the domain of food safety with specific reference to mycotoxin remediation. By leveraging the value-sensitive design approach, we described various strategies for analyzing the ethical implications of nanotechnology-based innovations in mycotoxin remediation. Through comprehensive ethics technology assessment, nanotechnology-based innovations can be guided toward becoming more value-oriented, thereby making substantial contributions to social progress.

(1) Background: Triggering receptor expressed on myeloid cells 2 (TREM2) is involved in neu-roinflammation and HIV-associated neurocognitive impairment (NCI). People with HIV (PWH) using cannabis exhibit lower inflammation and neurological disorders. We hypothesized TREM2 dysfunction mediates HIV neuropathogenesis and can be reversed by cannabinoids. (2) Methods: EcoHIV-infected wildtype (WT) and TREM2R47H mutant mice were used to study HIV's impact on TREM2 and behavior. TREM2 and related gene expressions were examined in mono-cyte-derived macrophages (MDMs) from PWH (n=42) and people without HIV (PWoH; n=19) with varying cannabis use via RNA sequencing and qPCR. Differences in membrane-bound and soluble TREM2 (sTREM2) were evaluated using immunocytochemistry (ICC) and ELISA. (3) Results: EcoHIV increased immature and C-terminal fragment forms of TREM2 in WT mice but not in TREM2R47H mice, with increased IBA1 protein in TREM2R47H hippocampi, correlating with worse memory test performance. TREM2 mRNA levels increased with age in PWoH but not PWH. Cannabidiol (CBD) treatment increased TREM2 mRNA alone and with IL1β. RNA-seq showed upregulation of TREM2-related transcripts in cannabis-using PWH compared to naïve controls. IL1β increased sTREM2 and reduced membrane-bound TREM2, effects partially re-versed by CBD. (4) Conclusions: These findings suggest HIV affects TREM2 expression modu-lated by cannabis and CBD, offering insights for therapeutic strategies.

Studies and opinion articles present unequal conclusions concerning empathy and morality, mainly because a somewhat heterogeneous and foggy conceptual approach prevails. This scoping review aims to analyse the relationship between empathy and morality and to present a novel conceptual model of empathy applied to moral decisions.A search in PsycINFO, Scopus and PubMed identified articles addressing the relationship between empathy and morality.Thirty-two articles were included. We find an absence of a consensual definition of empathy. It is commonly defined as a predominant emotional process and a factor of bias and prejudice in moral decisions.According to our conceptual model, empathy is a distinct, complex human neuropsychological capacity that mobilises and is dependent on the proper functioning of several brain areas and balances the scales on which are Emotion and Reason, enabling the most thoughtful moral decisions possible in diverse circumstances and contexts.

Background: Virtual Reality (VR) is an emerging tool in the management of anxiety, one of the most disturbing symptoms of Alcohol Use Disorder (AUD), which often leads to relapse. Still, patients with Alcohol Use Disorder frequently have a history of Acute Symptomatic Seizures, and they are subsequently excluded from studies using VR because of the hypothesized fear of inducing photosensitive seizures. The first part of this narrative review explores the pathophysiological mechanisms of seizures associated with AUD, specifically acute symptomatic seizures. In contrast, the second part explores virtual reality’s safe use in seizure-prone individuals, highlighting that the current state-of-the-art is based on a biased per-ception and old epidemiological data from studies conducted on photosensitive seizures in the late 90s. VR exposure has yet to be reported as triggering seizures within known pharmacovigilance databases. Significance: The implications weigh heavily on VR research currently associated with this significant adverse event. Further studies are necessary to address the risk of seizures triggered by VR in patients predisposed to developing seizures, like alcohol use disorder patients with a history of acute symptomatic seizures. Such research is essential to ensure that the potential benefits of Virtual Reality as a tool for managing anxiety in individuals with alcohol use disorder and acute symptomatic seizures are not unduly restricted. Furthermore, AUD can also serve as an intervention model feasible to de-bias attitudes toward the current lack of evidence base concerning the significant adverse events of VR-induced seizures, therefore facilitating the clinical implementation of this unharnessed digital treatment interface.

Dental agenesis is one of the most common developmental anomaly in humans and it is frequently as-sociated with several other oral abnormalities. The present case describes nonfamilial agenesis of per-manent teeth in a twenty-one-year-old boy, with no apparent systemic abnormalities. The treatment in-cluded a personalized and interdisciplinary approach by the means of endodontics, orthodontics, im-plants supported restorations and prosthetic treatments. The treatment plan was thoroughly elaborated using photographic analysis, study models, orthopantomogram, CBCT and cephalograms. Virtual smile design, diagnostic waxing, and mock-up previsualized the treatment objectives. The edentulous spaces were reconstructed by inserting dental implants, and monolithic Zirconia implant supported restorations. The final results showed a highly aesthetic and functional rehabilitation. Periodic checkups have shown that the stability of the result is well maintained and that the implant supported restorations are an op-timal solution for patients with multiple anodontia.

Lung cancer (LC) continues to be an important public health problem being the most common form of cancer and a major cause of cancer deaths worldwide. Despite the great bulk of research to identify genetic susceptibility genes by genome-wide association studies, only few loci associated to nicotine dependence have been consistently replicated. Our previously published study in few phenotypically discordant sib-pairs identified a combination of germline truncating mutations in known cancer susceptibility genes in never smoker early-onset LC patient does not present in their healthy sib. These results firstly demonstrated the presence of an oligogenic combination of disrupted cancer predisposing genes in non-smokers patients, giving experimental support to a model of a “private genetic epidemiology”. Here, we used a combination of whole-exome and RNA sequencing coupled with a discordant sib’s model in a novel cohort of pairs of never-smokers early-onset LC patients and in their healthy sibs used as controls. We selected rare germline variants predicted as deleterious by CADD and SVM bio-informatics tools and absent in the healthy sib. Overall, we identified an average of 200 variants per patient, about 10 of which in cancer predisposing genes. In most of them, RNA sequencing data reinforced the pathogenic role of the identified variants showing: i) downregulation in LC tissue (indicating “second hit” in tumor suppressor genes); ii) upregulation in cancer tissue (likely oncogene); iii) downregulation in both normal and cancer tissue (indicating transcript instability). The combination of the two techniques demonstrates that each patient has an average of six (with a range from four to eight) private mutations with functional effect in tumor predisposing genes. The presence of a unique combination of disrupting events in the affected subjects may explain the absence of familial clustering of non-small cell lung cancer. In conclusion, these findings indicate that each patient has his/her own “predisposing signature” to cancer development and suggest the use of personalized therapeutic strategies in lung cancer.

Epigenetics, the study of heritable changes in gene expression that do not involve alterations to the DNA sequence, is revolutionizing our understanding of psychiatric disorders. This article provides a comprehensive overview of the role of epigenetics in psychiatry, discussing its implications for genomics, evolution, inheritance patterns, and the development of biomarkers. Epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNAs, are explored in the context of psychiatric conditions such as depression, schizophrenia, and post-traumatic stress disorder (PTSD). The discussion highlights how epigenetic modifications can influence brain dynamics, as measured by electroencephalography (EEG), and how artificial intelligence (AI) can accelerate the development of treatment options. The potential for epigenetic biomarkers to improve diagnosis, prognosis, and treatment is emphasized, along with the role of behavioral interventions in inducing beneficial epigenetic modifications. Future directions in epigenetic research, including the development of epigenetic therapies and the elucidation of molecular mechanisms underlying epigenetic inheritance, are also discussed. This article underscores the transformative potential of epigenetics in advancing our understanding of mental health and disease, paving the way for novel therapeutic interventions.

Defensive behavior is a function of specific survival circuits, the “aversive brain system”, that are thought to be conserved across vertebrates, and involve threat detection and the organization of defensive responses to reduce or eliminate threat. In mammals, these circuits involve amygdalar and hypothalamic subnuclei and midbrain circuits. The increased interest in teleost fishes as model organisms in neuroscience created a demand to understand which brain circuits are involved in defensive behavior. Telencephalic and habenular circuits represent a “forebrain circuit” for threat processing and organization of responses, being important to mounting appropriate coping responses. Specific hypothalamic circuits organize neuroendocrine and neurovegetative outputs, but are the less well-studied in fish. A “midbrain circuit” is represented by projections to interneurons in the optic tectum which mediate fast escape responses via projections to the central gray and/or the brainstem escape network. Threatening stimuli (especially visual stimuli) can bypass the “high road” and directly activate this system, initiating escape responses. Increased attention to these circuits in an evolutionary framework is still needed.

(1) Background The SKT is a short cognitive performance test designed to assess impairments in memory and cognitive abilities such as attention and speed of information processing. In 2019, new regression-based norms for the English version of the SKT were calculated applying data from older cognitively healthy adults living in the US, Ireland and Australia (the norming sample) The study has two aims: to establish valid cut-offs for distinguishing between no cognitive impairment, mild cognitive impairment (MCI) and dementia (1), and to cross-validate the new norms for detecting MCI and dementia (2) in a community sample of older adults with clinical diagnoses; (2)Methods: The validation sample included 142 older adults (mean age=87.7, SD=3.55) from the Sydney Memory and Aging Study (MAS Study). Participants were classified as having normal cognition, MCI, or dementia through a consensus diagnosis as well as by the SKT; (3)Results: The sensitivity of the SKT for the differentiation of cognitive impairment (MCI or dementia) from normal cognition was 80.6%. The convergence between the SKT and the consensus diagnoses was 60.1% for all three diagnostic groups. The correlation between the SKT and the Addenbrooke’s Cognitive Examination III (ACE-III), a well validated measure of cognitive ability in older adults, was r = 0.3;. (4) Conclusions: In sum, it can be stated that the SKT is a valid tool for detecting early stages of cognitive impairment, performing very well in discriminating between no cognitive impairment and cognitive impairment (MCI or dementia).

In China, preschool teachers have a significant influence on the development of young children aged 3-6. It is imperative to understand their mental health and the factors associated with it to inform policies, optimize their mental well-being, and support their job performance. This study aimed to investigate the factors contributing to anxiety symptoms among preschool teachers. A sample of 393 Chinese preschool teachers (279 females, 114 males) aged 21-56 completed online questionnaires collecting their socio-demographic and work-related information and assessing anxiety symptoms, interpersonal difficulties, personality traits, perceived stress, resilience, and inner strength. Pearson correlation and multiple linear regression analyses identified significant predictors of anxiety symptoms. The prevalence of anxiety symptoms among the studied cohort was found to be 12.2%. Statistically significant factors positively correlated with anxiety symptoms included objective work-related stress (B=0.149, p<.001), interpersonal difficulties (B=0.921, p<.001), perceived stress (B=0.108, p=.001), and neuroticism (B=0.071, p=.002). The findings highlight the urgent need for measures to reduce work-related stress and anxiety. However, when negative mental health predictors were included, the effect of positive psychological factors became nullified. Positive mental health might have a moderating role in such a negative mental health outcome as anxiety. Therefore, further research is required to understand the impact of positive mental health factors more clearly.

The field of personalized medicine is undergoing a transformative shift through the integration of multi-omics data, which encompasses genomics, transcriptomics, proteomics, and metabolomics. This synergy allows for a comprehensive understanding of individual health by analyzing genetic, molecular, and biochemical profiles. The generation and integration of multi-omics data enable more precise and tailored therapeutic strategies, improving the efficacy of treatments and reducing adverse effects. However, several challenges hinder the full realization of personalized medicine. Key hurdles include the complexity of data integration across different omics layers, the need for advanced computational tools, and the high cost of comprehensive data generation. Additionally, issues related to data privacy, standardization, and the need for robust validation in diverse populations remain significant obstacles. Looking ahead, the future of personalized medicine promises advancements in technology and methodologies that will address these challenges. Emerging innovations in data analytics, machine learning, and high-throughput sequencing are expected to enhance the integration of multi-omics data, making personalized medicine more accessible and effective. Collaborative efforts among researchers, clinicians, and industry stakeholders are crucial to overcoming these hurdles and fully harnessing the potential of multi-omics for individualized healthcare.

This paper discusses the application of artificial intelligence in imaging omics, especially in cancer research. Imaging omics enables detailed analysis of spatial and temporal heterogeneity of tumours through high-throughput extraction of quantitative features from medical images such as MRI, PET, and CT. This paper focuses on applying PARKS systems to automate the recognition, segmentation, and extraction of image features, significantly enhancing the capabilities of clinical decision support systems (CDSS). The future direction is to establish a robust network infrastructure for radiology Medication-led Health care (RLHC) to facilitate the development and application of personalised treatment protocols, and to improve diagnostic accuracy, prognosis assessment, and treatment recommendations by uploading quantitative image features to a shared database and comparing them with historical images.

The success of deep learning (DL) in offline brain-computer interfaces (BCIs) has not yet translated into efficient online applications. This is due to three primary challenges. First, most DL solutions are designed for offline decoding, making the transition to online decoding complex and unclear. Second, the use of sliding windows in online decoding increases the computational complexity of DL training. Third, DL models typically require large amounts of training data, which are often scarce in BCI applications. To address these issues and enable real-time decoding, even across different subjects without calibration data, we first introduce a novel approach called real-time adaptive pooling (RAP). RAP modifies the pooling layers of existing offline DL models towards the online decoding requirements. Additionally, it significantly reduces the computational demand during training by jointly decoding consecutive windows. To reduce the amount of training data required, our approach leverages different levels of domain adaptation. We show how different settings enable different adaptation solutions. The results demonstrate that our approach is both powerful and can be calibration-free, providing a robust and practical solution for real-time BCI applications. These findings pave the way for the development of co-adaptive and highly efficient DL-based online BCI systems.

The shift towards Personalized Cancer Medicine (PCM) represents a significant transformation in cancer care, emphasizing tailored treatments based on genetic understanding of cancer at the cellular level. This review draws on recent literature to explore key factors influencing PCM implementation, highlighting the role of innovative leadership, interdisciplinary collaboration, and coordinated funding and regulatory strategies. Success in PCM relies on overcoming challenges such as integrating diverse medical disciplines, securing sustainable investment for shared infrastructures, and navigating complex regulatory landscapes. Effective leadership is crucial for fostering a culture of innovation and teamwork, essential for translating complex biological insights into personalized treatment strategies. The transition to PCM necessitates not only organizational adaptation but also the development of new professional roles and training programs, underscoring the need for a multidisciplinary approach and the importance of team science in overcoming the limitations of traditional medical paradigms. The conclusion underscores that PCM's success hinges on creating collaborative environments that support innovation, adaptability, and shared vision among all stakeholders involved in cancer care.

This study aimed to evaluate the safety and tolerability of STP1, a combination of ibudilast and bumetanide, tailored for the treatment of a specific subgroup of patients with Autism Spectrum Disorder (ASD), namely ASD Phenotype 1 (ASD-Phen1). We conducted a randomized, double-blind, placebo-controlled, parallel-group phase 1b study with two 14-day treatment phases (registered at clinicaltrials.gov as NCT04644003). Nine ASD-Phen1 patients were administered STP1, while three received a placebo. We assessed safety and tolerability, along with electrophysiological markers, such as EEG, Auditory Habituation, and Auditory Chirp Synchronization, to better understand STP1's mechanism of action. Additionally, we used several clinical scales to measure treatment outcomes. The results showed that STP1 was safe and well-tolerated, with electrophysiological markers indicating a significant and dose-related reduction of gamma power in the whole brain and in brain areas associated with executive function and memory. Treatment with STP1 also increased alpha 2 power in frontal and occipital regions and improved habituation and neural synchronization to auditory chirps. Although numerical improvements were observed in several clinical scales, they did not reach statistical significance. Overall, this study suggests that STP1 is safe and well-tolerated in ASD-Phen1 patients and shows indirect target engagement in ASD brain regions of interest.

The present study explored whether exposure to complex childhood trauma (CCT) is reflected in the resting-state electroencephalography (EEG) temporal alpha power of complex trauma-exposed adolescents, given the association of temporal alpha with fear circuitry (learning and conditioning) in a sample of 25 adolescents and similar controls, ages 12-17 years. Both trauma and psychopathology were screened or assessed, and resting-state EEG was recorded, following a preregistered protocol for data collection. Temporal alpha power, corresponding to T5 and T6 electrode location (10-20 international system), was extracted from resting-state EEG in both eyes-open and eyes-closed conditions. We found that in the eyes-open condition, right, but not left, temporal alpha was significantly higher in adolescents exposed to CCT, relative to healthy controls, suggesting that childhood trauma exposure may have a measurable impact on alpha oscillatory patterns, specifically in the right temporal region. Our study highlights the importance of considering neural markers, such as temporal alpha power, in understanding the long-term consequences of CCT exposure in developmental samples, with possible important clinical implications in guiding neuroregulation interventions.

The social fear conditioning (SFC) paradigm, which is an animal model of social anxiety disorder, has been extensively used to investigate the cellular and molecular mechanisms underlying the psychopathology of this disorder. Studies using the SFC paradigm have suggested that the lateral septum plays a pivotal role in regulating social fear. While several lines of evidence have indicated the involvement of various neuronal mechanisms within the LS in modulating social fear, the role played by LS astrocytes in the tripartite synapses in regulating social fear expression is not yet fully understood. Over the years, astrocytes have emerged as key players in regulating synaptic transmission and a plethora of animal behaviors. Given their dynamic morphological and molecular response to various stimuli, studying astrocyte morphology remains an excellent tool for understanding their role in brain function and disease. By applying immunofluorescent-immunohistochemical methods, here we describe a protocol to characterize changes in the morphology of astrocytes in response to social fear acquisition using confocal microscopy.

Background: Autism spectrum disorder (ASD) is a persistent neurodevelopment disorder frequently co-occurring with Attention-Deficit/Hyperactivity Disorder (ADHD) and behavior-related disorders. While behavioral therapy is the first-line option to manage ASD core symptoms, pharmacological therapy is sometimes needed to treat acute problems, such as agitation and aggressive behaviors. Recent guidelines recommend neuroleptics to reduce psychomotor agitation in people with ASD. However, since children with ASD are often drug-resistant, alternative treatments are often justified. Reports from literature showed that intra-venous valproate (IV-VPA) can be effective in reducing agitation in psychiatric patients, with lower frequency of adverse events compared to convention-al treatments. However, since findings are occasionally inconsistent, IV-VPA is not an approved option in clinical psychiatry. We aim at improving the knowledge on the IV-VPA treatment option in emergency psychiatry in the pediatric age. Methods: We report the case of a 11-year-old boy suffering from a complex neurodevelopmental condition, who experienced a psychotic episode with severe aggressive and disruptive behaviors, successfully treated with IV-VPA. Besides, we conducted an up-dated literature review on this topic. Conclusion: In our case, first-line therapies proved to be ineffective. On the contrary, IV-VPA led to a safe and prompt clinical success, in line with other reports. Based on our literature review, IV-VPA can be highly effective and can reduce the risk of adverse events that frequently occur with the use of high-dose standard medications in emergency psychiatry.

Background: Assessing the impact of bone health clinical management in breast cancer (BC) patients receiving adjuvant endocrine therapy and designing a personalized clinical pathway to reduce bone loss, in an Italian research hospital. Methods: The primary endpoint was to assess (through the process improvement organizational method) the clinical pathway that post-surgical BC patients prescribed with endocrine therapy undergo to prevent bone loss. The secondary endpoint was to design a personalized clinical pathway for a prompt implementation of guidelines, to assess and possibly prescribe antiresorptive therapy. Results: During the first year of the new diagnostic therapeutic assistance pathway execution, an 60% increase in Dual-Energy X-ray Absorptiometry evaluations within 30 days and a 39.5% increase in antiresorptive therapy prescription within 90 days (since prescription of endocrine therapy) were shown, thus increasing patients’ compliance. Conclusion: Case managers and bone health specialists in this context can improve patients’ adherence to therapies and bone health, helping physicians to expand their collaboration.

Fragile X syndrome (FXS) is caused by the full mutation in the FMR1 gene on the Xq27.3 chromosome region. It is the most common monogenic cause of Autism Spectrum Disorder (ASD) and inherited intellectual disability (ID). Besides ASD, ID and other issues, individuals with FXS may exhibit sleep problems and impairment of circadian rhythm (CR). The Drosophila melanogaster models of FXS, such as dFMR1B55, present excellent model for research in the FXS field. During this study, sleep pattern and CR in dFMR1B55 mutants were analyzed, using a new platform based on continuous high-resolution videography in integration with a highly-customized version of software. This methodology provides more sensitive results, which could be crucial for all further research in this model of fruit flies. The study revealed that dFMR1 B55 male mutants can be considered weak rhythmic flies rather than totally arrhythmic, and present a good alternative animal model of genetic disorder, which includes impairment of CR and sleep behavior. The combination of videography and software used in the current study should be recommended as a gold-standard methodology for such further research.

Rectal cancer presents a significant burden globally, often requiring multimodal therapy for locally advanced cases. Long-course chemoradiotherapy (LCRT) and short-course radiotherapy (SCRT) followed by surgery have been conventional neoadjuvant approaches. Recent trials favor LCRT due to improved local control. However, tumor distant recurrence remains a concern, prompting exploration of Total Neoadjuvant Therapy (TNT) as a comprehensive treatment strat-egy. Immune checkpoint inhibitors (ICIs) show promise, particularly in mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) tumors, potentially revolutionizing neoadjuvant regimens. Non-operative management (NOM) represents a viable alternative post-neoadjuvant therapy for selected patients achieving clinical complete response (cCR). Additionally, monitoring minimal residual disease (MRD) using circulating tumor DNA (ctDNA) emerges as a non-invasive method for treatment response assessment. This review synthesizes current evidence on TNT, ICIs, NOM and ctDNA, elucidating their implications for rectal cancer management and highlighting avenues for future research and clinical application.

It is estimated that pancreatic cancer will be the 2^nd leading cause of cancer-related deaths globally by 2030, highlighting the ongoing lack of effective treatment options in this devastating condition. There is a lack of reliable prognostic or predictive markers in pancreatic cancer to guide management decisions, whether for systemic chemotherapy, molecularly targeted therapies, or immunotherapies. To date, the results for targeted agents and immunotherapies in unselected populations of chemo-refractory pancreatic cancer have not met expectations. The reasons for this lack of efficacy of immunotherapy in pancreatic cancer are incompletely understood. The challenges in pancreatic cancer include the physical barrier created by the dense desmoplastic stroma surrounding the tumor, chemokine-mediated exclusion of T cells, poor antigenicity, paucity of infiltrating T cells within the tumor, ultimately leading to an immunosuppressive microenvironment. A better understanding of the role of inflammation in pancreatic cancer, its tumor microenvironment and individualized patient-related features, be they molecular, clinical or histopathological would enable a more effective tailored approach to the management of pancreatic cancer. In this review, the role of inflammation, the immune tumor microenvironment and potential immune biomarkers in pancreatic cancer are explored.

This study addresses the challenge of treating skin cancer effectively, especially in visible areas like the face, where traditional methods may be undesirable. Current options, including surgery and radiation therapy, have limitations such as complexity, expense, and imprecise dose delivery. The proposed solution involves additively manufacturing personalized patches using diagnostic imaging data, offering a targeted and controlled dose of beta-emitting isotopes like Y-90. The patches, tailored to the tumor's shape and depth, aim to minimize damage to healthy tissues and structures. Through 3D printing technology we demonstrated the feasibility of creating individualized applicators filled with radioisotopes, that have the potential to deliver therapeutic doses while ensuring patient comfort and affordability. This innovative approach, based on radiation delivery simulations, offers a promising future alternative to conventional radiation therapy methods. Clinical trials are required to validate its efficacy and safety, but the potential for reduced radiation exposure and enhanced treatment precision positions this personalized and targeted therapy as a valuable advancement in skin cancer treatment.

Fragile X syndrome (FXS), the most common monogenic cause of inherited intellectual disability and autism spectrum disorder, is caused by a full mutation (&gt;200 CGG repeats) in the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene. Individuals with FXS experience a wide range of challenges related to social interaction (SI). Animal models, such as Drosophila melanogaster model for FXS where the only ortholog of human FMR1 (dFMR1) is mutated, have played a crucial role in understanding of FXS. The aim of this study was to investigate SI in the dFMR1B55 mutants using the novel Drosophila Shallow Chamber and a Python data processing pipeline based on social network analysis (SNA). In comparison with wild-type flies (w1118), SNA analysis in dFMR1B55 mutants revealed hypoactivity, fewer connections in their networks, a lower ability to efficiently transmit information, fewer alternative pathways for information transmission, a higher variability in the number of interactions they achieved, and tended to stay near the boundaries of the testing chamber. These observed alterations indicate the presence of characteristic strain-dependent social networks in dFMR1B55 flies, commonly referred to as the group phenotype. Finally, a combination of novel research tools is a valuable method for SI research in fruit flies.

Psoriasis is a chronic, multisystem, inflammatory disease. The typical clinical cutaneous manifestation of psoriasis is scaly erythema or plaque, limited or widely distributed. However, psoriasis is far beyond the skin involvement and provides many challenges, including associated comorbidities. In this review, we classify psoriasis as cutaneous and systemic psoriasis, according to the clinical diversity and associated comorbid diseases, and recommend classification criteria for psoriasis. The key objective of this novel classification is to raise awareness of the complexity of this multifaceted disease and help to better understand and manage this complex disease comprehensively.

Background: Many clinical conditions are affected by meteorological factors and climate changes. Psychiatric disorders are large contributors to the global disease burden, but the literature on the impact of climate changes on mental health is limited. The aim of this study is to investigate the correlation between rising temperatures and admissions for acute exacerbations of psychiatric disorders. Methods: Data were collected for summer months of years 2013 to 2022. Mean monthly tempera-tures were obtained from the meteorological station of the Department of Physics of the Universi-ty of Turin. Data on patients admitted to the acute psychiatric unit of San Luigi Gonzaga Univer-sity Hospital (Turin, Italy) were extracted from the hospital registry. Linear regression analyses were used to investigate the correlation between temperature and number of admissions. Results: A total of 1600 admissions to our psychiatric ward were recorded. Mean monthly temper-ature and monthly number of admissions were directly correlated (P = 0.0020). The correlation between temperature and admissions was significant for the subgroup of admissions due to Bipo-lar Disorders (BD) (P=0.0011), but not for Schizophrenia (P=0.6070) (SCZ) or Major Depressive Disorder (MDD) (P=0.0588). Conclusions: These results confirm the impact of meteorological factors on mental disorders, and in particular on the course of BD. This provides new insights into etiopathological mechanisms and can contribute to improved follow up and relapse prevention.

Background/Objectives: The global burden of colorectal cancer (CRC) is projected to increase by 2040, highlighting the need for prevention strategies, early detection and adequate follow. The aim of this study was to provide an overview of the progress in personalized medicine of CRC in Serbia, with results and insights from the Institute for Oncology and Radiology of Serbia (IORS), and to propose guidance for tackling observed challenges in the future. Methods: Epidemiological data was derived from official global and national cancer registries and IORS electronic medical records. Germline genetic testing for Lynch syndrome was performed by Next Generation Sequencing. RAS and BRAF mutation analyses were performed using qPCR diagnostic kits. Results: Epidemiology and risk factors, prevention and early detection programs, as well as treatment options and scientific advances have been described in detail. Out of 103 patients who underwent germline testing for Lynch syndrome, 19 (18.4%) had a pathogenic or likely pathogenic mutation in one of the MMR genes, and 8 (7.8%) in other CRC-associated genes (APC, CHEK2, MUTYH). Of 6369 tested patients, 50.43% had a mutation in KRAS or NRAS genes, while 9.54% had the V600 mutation in the BRAF gene. Conclusions: Although significant improvements in CRC management have occurred globally in recent years, the high incidence of young-onset CRC and the growing elderly population due to a rise in life expectancy require a strategic approach leading to population-based systemic solutions, especially important for countries with limited health care resources as Serbia.

This study analysed trends of first-time patients visiting the paediatric psychiatry clinic in a university hospital. The medical records from 2009 to 2016 of first-time patients visiting the Kyung Hee university hospital were reviewed, focusing on children in grades 1–12. We analysed the prevalence rate of psychiatric disorders per 100,000 general populations by gender and grade, and the characteristics of patients who sought outpatient care more than three times. The study included 1,467 participants, of which 931 were males (63.5%). The number of male patients per 100,000 populations significantly decreased from 4.14 in 2009 to 2.03 in 2016. While hyperkinetic disorders had the highest prevalence in males, neurotic disorders were most frequent in females. Prevalence of disruptive behaviour disorders in males and mental retardations in females decreased significantly during the study period. The factors affecting continuity were being female, studying in grades 7–12, and diagnosis of depressive, hyperkinetic, and tic disorders. Physicians should consider the new paediatric patients’ gender, grade, and expected diagnosis from their first visit to improve treatment compliance.

There is currently no effective treatment strategy for the recurrent/metastatic adenoid cystic carcinoma (R/M ACC). Furthermore, recent single-agent and combination immunotherapy trials have failed in unselected ACC cohorts unlike non-ACC salivary gland cancers. Genomic profiling revealed no actionable targets but NOTCH1 and KDM6A frameshift and CTCF splice site mutations (no MYB/L fusion) with a low TMB, MSS and negative PD-L1. We recommended anti-PD-1 plus anti-CTLA-4 combination based on TMB 2-fold greater than median TMB in ACC, tumor harboring multiple immunogenic frameshift or splice site mutations, and PD-L1 negativity. Accordingly, we achieved a complete response in a radiotherapy and chemotherapy-refractory patient with locally recurrent lacrimal gland ACC and lung metastasis following personalized immunotherapy in combination with integrative therapeutics. Therefore, it is crucial to assess not only conventional immune biomarkers but also patient-specific parameters.

Sweat rate and electrolyte losses have a large inter-individual variability, a personalized approach to hydration can overcome this issue to meet an individual’s needs. This study aimed to investigate the effects of personalized hydration strategy (PHS) on fluid balance and intermittent exercise performance. Twelve participants conducted 11 laboratory visits including a VO2max test and two 5-day trial arms under normothermic (NOR) or hyperthermic (HYP) environmental conditions. Each arm began with 3-day of familiarization exercise following by two random exercise trials with a either PHS or control (CON). Then, participants crossed-over to the second arm for: NOR+PHS, NOR+CON, HYP+PHS, and HYP+CON. The PHS was prescribed according to participants’ fluid and sweat sodium losses. CON drank ad-libitum of commercially-available electrolyte solution. Exercise trials consisted of two phases: 1) 45min constant workload; 2) high-intensity intermittent exercise (HIIT) until exhaustion. PHS had a significantly greater fluid intake compared to CON. HYP+CON produced the lowest sweat sodium concentration. HYP+PHS had a lower thirst perception and a longer HIIT compared to HYP+CON. Thus, PHS reinforces fluid intake and successfully optimizes hydration status, regardless of environmental conditions. PHS may be or is an important factor to preventing negative physiological consequences during high-intensity exercise in the heat.

Based on non-invasive neuroimaging techniques and graph theory-based network analyses, many researchers have tried to use small-world network model to elucidate sex differences in the brain. This manuscript aims to compile the related research findings from the past few years and summarize the sex differences in human brain networks from the perspective of small-world properties. We reviewed published reports examining altered small-world properties in both the functional and structural brain networks between males and females. Based on four patterns of altered small-world properties proposed--randomization, regularization, stronger small-worldization and weaker small-worldization, we found that current results point to a significant trend toward more regularization in females and more randomization in males in the functional brain networks. As for particular topological properties, the most consistent findings include a significant shift toward higher global efficiency in males and higher local efficiency in females in the functional network studies. On the other hand, there seems to be no consensus to date on the sex differences in small-world properties of the structural brain networks. Nevertheless, we noticed that the sample sizes in many published studies are limited, and future studies with larger samples are warranted to obtain more reliable results. We anticipate that the conclusions in this manuscript will contribute to a deeper understanding of neurobiological mechanisms underlying the sex differences in the brain.

Although the dopamine hypothesis of schizophrenia explains the effects of all the available antipsychotics in clinical use, there is an increasing need for developing new drugs for the treatment of positive, negative, and cognitive symptoms of chronic psychoses. Xanomeline-trospium (KarXT) is a drug combination that is based on the essential role played by acetylcholine in the regulation of cognitive processes and the interactions between this neurotransmitter and other signaling pathways in the central nervous system, with a potential role in the onset of schizophrenia, Alzheimer’s disease, and substance use disorders. A systematic literature review that included four electronic databases (PubMed, Cochrane, Clarivate/Web of Science, and Google Scholar) and the US National Library of Medicine database for clinical trials detected 21 sources referring to 14 studies focused on KarXT, out of which only four have published results. Based on the results of these trials, the short-term efficacy and tolerability of xanomeline-trospium are good, but more data is needed before this drug combination may be recommended for clinical use. However, on a theoretical level, the exploration of KarXT is useful for increasing the interest of researchers in finding new, non-dopaminergic, antipsychotics that could be used either as monotherapy or as add-on drugs.

The aims of this systematic review and meta-analysis were to evaluate the risk of inmates with mental disorder of being placed into disciplinary confinement (DC) and its effect on mental health. A systematic search of studies was performed in PubMed, PsycINFO, Web of Science, and Google Scholar. The meta-analysis was conducted using random-effects models. Heterogeneity among study point estimates was assessed with Q statistics and quantified with I2 index. Publication bias was assessed with Egger’s test. Quality assessment was based on the GRADE Checklist for observational studies. Guidelines from Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were followed throughout. First, a meta-analysis of 5 articles including 27,455 inmates showed than incarcerated individuals with a mental disorder were 1.23 times (OR=1.23, CI=1.10; 1.38) more likely to be placed in DC than incarcerated individuals without a mental disorder. Particularly, having a severe mental disorder (OR=1.31, p&lt;0.001), a personality disorder (OR=1.66, p&lt;0.001) and having previously received mental health services (OR=1.16, p=0.024) increased the risk of being placed in DC. Secondly, a systematic review of 5 articles including 171,300 inmates showed more psychological distress, psychiatric symptoms (self-harm, thought disorders, obsessive-compulsive symptoms), need for mental health services and hospitalizations in DC than the general correctional population. Considering the increased risk of placement in DC for incarcerated persons with a mental disorder and its deleterious effect on mental state, it is essential that correction officials create new safe interventions to manage these inmates and offer them proper mental health care to limit its use.

ADHD is a neurodevelopmental disorder that children and also adults can develop. A complex interplay of genetic and environmental factors may underlie interindividual variability in ADHD and potentially related aggressive behavior. Using high-resolution molecular biology techniques, we investigated the impact of some MAOA and SLC6A4 variations on ADHD and aggressive behavior in a group of 80 Italian children with ADHD and in 80 healthy controls.We found that homozygous genotypes of MAOA rs6323 and rs1137070 were associated with an increased risk of ADHD (p=0.02 and p=0.03, respectively), instead the heterozygous genotypes (GT of rs6323 and CT of rs1137030) (p=0.0002 and p=0.0006) were strongly linked to a lower risk of developing this disorder. In patients with aggressive behavior, we highligted only a weak negative association of both MAOA polymorphisms (heterozygous genotypes) with aggressiveness then, suggesting that these genotypes maybe protective towards specific changes in behavior (p=0.05). Interestingly, an increase of the GG genotype of rs6323 (p=0.01) and a decrease of GT genotype (p=0.0005) was also found in patients without aggressive behavior compared with controls. Regarding 5HTT gene genotyping, no allele and genotype differences have been detected among patients and controls. Our work shows that defining a genetic profile of ADHD may help to early detect those patients who are more vulnerable to ADHD and/or antisocial and aggressive behavior and to design precision-targeted therapies.

Background: Immunologic and neuro-inflammatory pathways have been found to play a major role in the pathogenesis of many neurological disorders such as epilepsy, proposing the use of novel therapeutic strategies. In the era of personalized medicine and in the face of the exhaustion of anti-seizure therapeutic resources it is worth looking at the current or future possibilities that neuroimmunomodulator or anti-inflammatory therapy can offer us in the management of patients with epilepsy. Methods: We performed a narrative review on the recent advances on the basic epileptogenic mechanisms related to the activation of immunity or neuroinflammation with special attention to current and future opportunities for novel treatments in epilepsy. Results: Neuroinflammation can be considered a universal phenomenon and occurs in structural, infectious, post-traumatic, autoimmune, or even genetically based epilepsies. The emerging research developed in recent years has allowed us to identify the main molecular pathways in-volved in these processes. These molecular pathways could constitute future therapeutic targets for epilepsy. Conclusions: Different drugs current or in development have demonstrated their capacity to inhibit or modulate molecular pathways involved in the immunologic or neuroinflammatory mechanisms described in epilepsy. Some of them should be tested in the future as possible antiepileptic drugs.

Today, LLMs are not good at personalization providing recommendation. They advise physicians and financial advisors to ask professionals in respective fields for help, even having user information available. Answering questions of software professionals, LLM needs to deliver in-depth answers with codes or algorithms, whereas for professionals in other fields would need definitions and main concepts. The intent of this chapter is to make LLM answer tailored to the needs of users, taking into account available information about them. To do that, we need to generalize available information about a person like her health record, maintaining the privacy of this person. We rely on meta-learning techniques to design a LLM prompt to produce a personalization prompt to obtain a suitable relevant information. Such “meta-prompt” is produced by generalization operation applied to available documents for the user. These documents need to be de-identified so that they are sufficient for personalization on one hand and will maintain user privacy on the other hand. The second neuro-symbolic technique to support personalization is abductive reasoning, acting in parallel to LLM fine-tuning. Traditional recommendation and personalization techniques as well as modern, deep learning – based are presented, and the comparison is drawn to the proposed approach. We also share the evaluation and comparative analyses of these approaches. We consider an example for how to build personalization LLM systems coming from Langchain platform. We will explore how to construct chains to form a personalization profile for a user and apply it to user search and recommendation requests.

Background: to assess the benefit of a deep inspiration breath hold (DIBH) over standard irradiation technique, and eventually to identify anatomical and/or treatment preplanning characteristics correlated with LAD dose. Methods: We retrospectively identified patients with left-sided breast cancer who underwent whole breast radiotherapy in DIBH. All patients had both plans in DIBH and free-breathing (FB). Receiving operating characteristics (ROC analysis) were performed to define the cut-off point of parameters to predict LAD maximum dose >10 Gy and LAD mean dose > 4 Gy. Areas under the curve (AUCs) were calculated for all variables. Post-test probability has been calculated to evaluate advantage for parameters combination. Results: One hundred ninety-seven patients were identified. LAD dose was significantly reduced in DIBH plans with maximum and mean dose reduced by 31.7% (mean value 3.5 Gy vs 4.8 Gy, p=<0.001) and 28.1% (mean value 8.2 Gy vs 12.8 Gy, p=<0.001) in DIBH plans compared to FB plans. The strongest predictor of LAD maximum dose > 10 Gy and a LAD mean dose > 4 Gy was the minimum distance of LAD from tangent open fields. Other parameters were lung volume and heart volume for LAD Dmax > 10 Gy and lung volume, heart volume and breast separation for LAD Dmean > 4 Gy. Conclusion: The dosimetric benefit of DIBH is valid for all patients and DIBH should be preferred for all left sided patients.

In today’s Web 2.0 era, online social media has become an integral part of our lives. In the course of the information revolution, the form of information has undergone a radical change, from simple text information to today’s integrated video, image, text and audio, and there has also been a great change in the way of dissemination and access, as people nowadays do not just rely on traditional media to passively receive information, but more actively and selectively obtain information from social media. Therefore, it has become a great challenge for us to effectively utilize these massive and integrated multi-modal media information to form an effective system of retrieval, browsing, analysis and usage. Unlike movies and traditional long-form video content, micro-videos are usually short in length, between a few seconds and tens of seconds, which allows users to quickly browse different contents and make full use of the fragmented time in their lives, while users can also share their micro-videos to their friends or the public, forming a unique social way. Video contains rich multimodal information, and fusing information from multiple modalities in a video recommendation task can improve the accuracy of the video recommendation task.According to the micro-video recommendation task, a new combinatorial network model is proposed to combine the discrete features of each modality into the overall features of various modalities through the network, and then fuse the various modal features to obtain the overall video features, which will be used for recommendation. In order to verify the effectiveness of the algorithm proposed in this paper, experiments are conducted in the public dataset, and it is shown the effectiveness of our model.

Informal dementia home caregiving is viewed negatively and can result in caregiver depression and anxiety from burnout, potentially compromising caregiving. Solutions are unclear, as caregiving relationships are unique—caregiver creation of a graphic memoir may help to mitigate the negative dementia narrative and reduce experienced burnout. This investigation examines the writing of a graphic memoir by one informal dementia home caregiver, created with the help of a cartoon illustrator and a publisher who edited, printed, and made the graphic memoir available at the psychiatric bookstore considered the largest in North America. Mother of the illustrator and the editor and publisher of this graphic memoir, this author provides the perspective taken in this investigation. The analysis, developed by this author, represents psychoanalytic narrative research, serving as the historical method. Aided by email threads between the publisher/caregiver, publisher/printer, and publisher/bookseller, and a published interview with the dementia caregiver are answers to how writing, illustrating, and publishing the graphic memoir affected the caregiver’s narrative reconstruction and burnout. Providing an example for other informal dementia home caregivers similarly to write and illustrate a publishable graphic memoir for their positive narrative reconstruction and to help decrease their depression and anxiety from burnout is the aim.

Gestational diabetes mellitus (GDM) triggers alterations in the maternal gut microbiome. Alongside metabolic shifts, microbial products may impact clinical factors and influence pregnancy outcomes. Here, we performed two separate analyses to integrate the maternal microbiome-metabolomic differences from a subset of the “Choosing Healthy Options in Carbohydrate Energy” (CHOICE) study. Women diagnosed with GDM were randomized to a diet higher in complex carbohydrates (CHOICE, n=18, 60% complex carbohydrate/25% fat/15% protein) or a conventional GDM diet (CONV, n=16, 40% carbohydrate/45% fat/15% protein). All meals were provided, diets were eucaloric, and fiber content was similar. CHOICE diet was associated with increases in TMAO, lysophosphotidylcholines, indoxyl sulfate, and several triglyceride (TG) species, while CONV diet was associated with higher plasma hippuric acid, aspartic acid, betaine, glutamic acid, indole propionic acid, and indoleacetic acid, suggesting that differences in lipid metabolism and tryptophan utilization pathways are linked to specific maternal diets. We also identified two latent metabolic groups not associated with either diet treatment: one metabolome associated with higher fasting glucose, and the other associated with higher fasting TGs after 7 weeks on either diet. Our study underscores the importance of utilizing dietary approaches to optimize maternal-fetal health outcomes in GDM treatment.

Children—Dependents in Social Construction Theory—are assessed within democracies regarding their ability to self-direct their behavior concerning their associated society. In this regard, childhood represents a lack of self-direction, a life period when people require the guidance and protection of adults. The assumed necessity of adults supervising children in democracies requires substantial social resources, reducing the self-direction of those charged with overseeing children. Given that self-direction defines the optimal experience of people within democratic society, finding ways to increase the self-direction of children is an individual and a social benefit. In this regard, smartphones have improved self-direction in children. How children have become empowered to self-direct their lives with smartphone use considering Social Construction Theory—as Advantaged, Contenders, or Deviants—is the focus of a scoping review conducted on “children, empowerment, smartphones” of the following databases: OVID, JSTOR, ProQuest, PubMed, Scopus, and Web of Science. The result is that children permitted to self-direct their activities aided by smartphone technology have comparable social behavior to adults positioned as Advantaged, Contenders, or Deviants and, as such they should be encouraged to utilize smartphone technology to improve their self-direction, as doing so will augment individual and caregiver self-direction, providing increased social benefit.

This study introduces the Data-Driven Personalized Learning Model (DDPLM), a sophisticated framework designed to enhance foreign language acquisition through the integration of big data analytics. Implemented within the educational platforms Edmodo and Duolingo, DDPLM utilizes real-time data processing to tailor learning paths and content dynamically to individual learner needs. Our findings indicate significant improvements in language learning efficiency, engagement, and retention. The model's adaptability across different digital environments showcases its potential scalability and effectiveness in various educational contexts. Additionally, the research addresses the critical role of personalized feedback and adaptive challenges in maintaining learner motivation and promoting deeper linguistic comprehension. The outcomes suggest that DDPLM significantly transforms traditional language education, making it more personalized, efficient, and aligned with individual learning preferences.

Diagnosis and treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in women remain insufficient. Fluctuations of reproductive hormones during the premenstrual period, postpartum period and (peri)menopause are neglected, even though they impact ADHD symptoms and as-sociated mood disorders [1]. Therefore, we created a female-specific treatment group for women with ADHD and premenstrual worsening of ADHD and/or mood symptoms. We describe the group programme and underlying rationale, offering a qualitative analysis of the participants’ evaluation. The 7 two-weekly sessions foreground the menstrual cycle and address several ADHD-specific topics in relation to this cyclical pattern: emotional regulation; impulsivity; setting boundaries, and triggers. Concurrently, women track their menstrual cycle and (fluctuating) ADHD and mood symptoms with an adjusted premenstrual calendar. In total, 18 women (25-47yrs) participated in three consecutive groups. We analysed the evaluation of the last group. Participants experienced the group as a safe and welcoming space. Recognition was valued by all. The topics discussed were deemed valuable and the structure suited them well. Completing the premenstrual calendar augmented awareness and recognition of individual cyclical symptoms. Discussing ADHD throughout the lifespan increased self-understanding. Participants took their menstrual cycle more seriously, prioritising self-acceptance and self-care in the luteal phase of the cycle. Exploring a cyclical approach in a group setting seems to be a positive addition to treatment for female ADHD.

Limited understanding exists regarding the intricate dynamics between the levels of social inhi-bition exhibited by both wives and husbands concerning their perceived family support and de-pressive symptoms, particularly within couples who are parents of children diagnosed with au-tism spectrum disorder (ASD). This study used the actor-partner, interdependence mediation model to analyze data collected from 397 pairs of Chinese parents with children diagnosed with ASD. The findings of the study revealed significant indirect actor effects, indicating that the levels of social inhibition exhibited by both wives and husbands were associated with their own de-pressive symptoms through their respective perceptions of family support. In general, the study did not find significant partner effects, except for some indirect effect (IE) of wives on their hus-bands' depressive symptoms through the wives' perceived social support. This observation sug-gests that cultural norms and role expectations within the family context may influence these dy-namics. These results underscore the potential importance of interventions aimed at addressing social inhibition and enhancing perceived family support to alleviate depressive symptoms in this population. Additionally, interventions targeting fathers should emphasize the importance of their involvement in parenting and collaboration with their partners in caring for children with ASD. Such collaborative efforts may contribute to improved outcomes for both parents and chil-dren within families affected by ASD.

Psychiatric disorders share the same pattern of longitudinal evolution and have courses that tend to be chronic and recurrent. These aspects of chronicity and longitudinal evolution of psychiatric disorders are currently studied under the neuroprogression framework. Interestingly, considering the plasticity of the brain, it is necessary to emphasize the bidirectional nature of neuroprogression. We review evidence highlighting alterations of the brain associated with the longitudinal evolution of psychiatric disorders from the framework of neuroplastic adaptation to pathology. This new framework highlights that substantial plasticity and remodelling may occur beyond the classic neuroprogressive framework, which is characterized only by loss of grey matter volume, decreased brain connectivity, and chronic inflammation. We also integrate the brain economy concept in the neuroplastic adaptation to pathology framework, emphasizing that to preserve its economy, i.e., function, the brain learns how to cope with the disease by adapting its architecture. This approach can disentangle both the specific pathophysiology of psychiatric symptoms and the adaptation to pathology, thus offering a new framework for both diagnosis and treatment.

Cancer cells are adept at reprogramming energy metabolism and the precise manifestation of this metabolic reprogramming exhibits heterogeneity across individuals (and from cell to cell). In this study, we analyzed the metabolic differences between interpersonal heterogeneous cancer phenotypes. We used divergence analysis on gene expression data of 1156 breast normal and tumor samples from The Cancer Genome Atlas (TCGA) and integrated this information with a genome-scale reconstruction of human metabolism to generate personalized, context-specific metabolic networks. Using this approach, we classified the samples into four distinct groups based on their metabolic profiles. Enrichment analysis of the subsystems indicated that amino acid metabolism, fatty acid oxidation, citric acid cycle, androgen and estrogen metabolism and ROS detoxification distinguished these four groups. Additionally, we developed a workflow to identify potential drugs that can selectively target genes associated with the reactions of interest. MG-132 (a proteasome inhibitor) and OSU-03012 (a celecoxib derivative) were the top-ranking drugs identified from our analysis and known to have anti-tumor activity. Our approach has the potential to provide mechanistic insights into cancer-specific metabolic dependencies, ultimately enabling the identification of potential drug targets for each patient independently, contributing to a rational personalized medicine approach.

Personalized medicine is an aspect of the P4 medicine (predictive, preventive, personalized and participatory) based precisely on the customization of all medical characters of each subject. In personalized medicine, the development of medical treatments and drugs is tailored to the individual characteristics and needs of each subject, according to the study of diseases at different scales from genotype to phenotype scale. To make concrete the goal of personalized medicine, it is necessary to employ high-throughput methodologies such as Next Generation Sequencing (NGS), Genome-Wide Association Studies (GWAS), Mass Spectrometry or Microarrays, that are able to investigate a single disease from a broader perspective. For example, by using genotyping microarrays (e.g. collections of Single Nucleotide Polymorphism - SNP) it is possible to uncover the reasons (i.e. mutation in genes) because a treatment works properly in some patients (for example absence of mutated genes), but it does not work (presence of mutated genes) in others. A side effect of high-throughput methodologies is the massive amount of data produced for each single experiment, that poses several challenges (e.g. high execution time and required memory) to bioinformatic software. Thus a main requirement of modern bioinformatic software is the use of good software engineering methods and efficient programming techniques, able to face those challenges, that include the use of parallel programming and efficient and compact data structures. Thus, to exploit all the potential of this massive amount of data in the short possible time (before that data becomes obsolete), the necessity to develop parallel software tools for efficient data collection and analysis arise. Moreover, due to the heterogeneity of the data produced by the different kinds of experimental platforms, it is necessary to automatize in a comprehensive software pipeline, the various steps that compose a bioinformatic analysis, such as: the preprocessing of raw data to remove noise or corrupted data; the annotation of data with external knowledge (e.g. Gene Ontology), and the integration of molecular data with clinical data. It should be noted that such steps are necessary to make statistical or data mining analysis more effective. This paper presents the design and the experimentation of a comprehensive software pipeline, named microPipe, for the preprocessing, annotation and analysis of microarray-based SNP genotyping data. A case study in pharmacogenomics is presented. The main advantages of using microPipe are: the reduction of errors that may happen when trying to make data compatible among different tools; the possibility to analyze in parallel huge datasets; the easy annotation and integration of data.

Colorectal cancer (CRC) is characterized by a pro-inflammatory microenvironment and features high energy supply molecules that assure tumor growth. A still underestimated macromolecule is the Inorganic Polyphosphate (iPolyP), a high-energy linear polymer that is ubiquitous in all forms of life. Made up of hundreds of repeated orthophosphate units, iPolyP is essential for a wide variety of functions in mammalian cells, including the regulation of proliferative signaling pathways. Some evidence has suggested its involvement in carcinogenesis, although more studies need to be pursued. In this study, we tested the role of iPolyP on CRC proliferation, using in-vitro and ex-vivo approaches, in order to evaluate its effect on tumor growth. We found that iPolyP is significantly increased in tumor tissues compared to the corresponding peritumoral counterparts. In addition, iPolyP signaling occurs through the TRPM8 receptor, promoting CRC cell proliferation. Pharmacological inhibition of TRPM8 or RNA interference experiments showed that the involvement of TRPM8 is essential, greater than that of the other two known iPolyP receptors, P2Y1 and RAGE. The presence of iPolyP drives cancer cells towards the mitotic phase of the cell cycle by enhancing the expression of ccnb1, which encodes for the Cyclin B protein. In-vitro 2D and 3D data reflected the ex-vivo results, obtained by the generation of CRC-derived organoids, which increased in size. These results indicate that iPolyP may be considered a novel and unexpected early biomarker supporting colorectal cancer cell proliferation.

Recently, the Portuguese parliament approved the decriminalisation of euthanasia for incurable illnesses. As the experiences of other countries show us, it will be a matter of time before mental disorders are addressed. Studying the phenomenon, particularly in vulnerable groups, in advance is essential for proper law drafting. Therefore, instruments which allow an objective assessment and comparison between groups must be available. This study aims to explore the validation of Faria's Attitude about Euthanasia scale in Portuguese older adult patients with mixed anxiety-depressive disorder. A sample of 114 older adult patients with mixed anxiety-depressive disorder collected by convenience in the Psychiatry Department of Senhora da Oliveira Hospital in Portugal was included. The pre-final version of the scale was tested in a small group with good results. The validity of the internal structure was analysed using exploratory factorial analysis. The internal consistency study verified reliability. For construct validity, we assessed the correlation with other validated scales measuring attitudes toward euthanasia, cognitive performance, personality and empathy. Attitude about euthanasia scale showed good internal consistency. One factor was retained in the principal component analysis. Significant correlations verified construct validity. The results support the scale's usefulness and validity. This study makes available a unique instrument to assess the overall tendency of the attitudes towards euthanasia in European-Portuguese, which can be used, for example, to compare Portuguese with Brazilian older adult psychiatric patients suffering from the same disorder. Furthermore, the adapted scale paves the way for other cross-cultural translations, adaptations, validations, and comparative analyses.

Geriatric decisional capacity assessment is a complex medico-legal activity that evaluates normal subjects involved in specific civil matter like wealth transfer, access to treatment or voluntary hospitalization. Our objective was to evaluate how geriatric extrajudicial capacity exams impacted a general psychiatric unit over a decade. We also assessed the value of a surrogate biomarker (neutrophils to lymphocyte ratio) as a screening factor in the capacity assessment process. 72 cases were assessed in one psychiatric unit over a decade (2009-2018). As population was fast ageing, the total number of capacity exams per year doubled in time. None of the subjects had an active diagnostic of severe cognitive impairment or active psychiatric disease. The percentage of subjects receiving an “absence of capacity” conclusion remained constant over time (approx. 20% of all cases). 81% of the subjects within this subgroup had a clinical diagnostic of mild cognitive impairment compared to 46% in the “presence of capacity” subgroup (p&lt;0.001). The surrogate biomarker neutrophils to lymphocyte ratio was significantly higher in the “absence of capacity” subgroup, mainly related to a cognitive impairment diagnostic. The ratio has to be validated by larger studies before to be included in the capacity assessment process as an early screening tool.

Mass spectrometry (MS) has revolutionized clinical chemistry, offering unparalleled capabilities for biomolecule analysis. This review explores the growing significance of MS, particularly when coupled with liquid chromatography (LC-MS), in identifying disease biomarkers and quantifying biomolecules for diagnostic and prognostic purposes. The unique advantages of MS in accurately identifying and quantifying diverse molecules have positioned it as a cornerstone in personalized medicine advancement. MS-based technologies have transformed precision medicine, enabling comprehensive understanding of disease mechanisms and patient-specific treatment responses. LC-MS has shown exceptional utility in analyzing complex biological matrices, while high-resolution MS has expanded analytical capabilities, allowing detection of low-abundance molecules and elucidation of complex biological pathways. The integration of MS with other techniques, such as ion mobility spectrometry, has opened new avenues for biomarker discovery and validation. As we progress towards precision medicine, MS-based technologies will be crucial in addressing the challenges of individualized patient care, driving innovations in disease diagnosis, prognosis, and treatment strategies.

Tumor cells evolve in a complex and heterogeneous environment composed of different cell types and an extracellular matrix. Current 2D culture methods are very limited in their ability to mimic the cancer cell environment. In recent years, various 3D models of cancer cells have been developed, notably in the form of spheroids/organoids, using scaffold or cancer-on-chip devices. However, these models have the disadvantage of not being able to precisely control the organization of multiple cell types in complex architecture and are sometimes not very reproducible in their production, and this is especially true for spheroids. Three-dimensional bioprinting can produce complex, multi-cellular, and reproducible constructs in which the matrix composition and rigidity can be adapted locally or globally to the tumor model studied. For these reasons, 3D bioprinting seems to be the technique of choice to mimic the tumor microenvironment in vivo as closely as possible. In this review, we discuss different 3D-bioprinting technologies, including bioinks and crosslinkers that can be used for in vitro cancer models, and the techniques used to study cells grown in hydrogels; finally, we provide some applications of bioprinted cancer models.

The value of landscape, as part of collective heritage, can be acquired by GIS due to the multilayer approach of the spatial configuration. Proficiency in geospatial technologies in order to collect, process, analyze, interpret, visualize and communicate geographic information is being increased by undergraduate and graduate students, but in particular by those who are training to become geography teachers at secondary education. This training can be carried out through personalized learning and distance learning methodology. Personalized GIS education aims to integrate students and enhance their understanding of landscape. Some teaching experiences are shown whereby opportunities offered by WebGIS will be described, through quantitative tools and techniques that will allow this modality of learning and improve its effectiveness. Results of this research show that students, through geospatial technologies, learn landscape as a diversity of elements but also the complexity of physical and human factors involved. Several conclusions will be highlighted: i) the contribution of geospatial training to education for sustainable development; ii) spatial analysis as a mean of skills acquisition about measures for landscape conservation; iii) expanding and applying acquired knowledge to other geographic spaces and different landscapes.

Patients with a psychotic disorder frequently report oral health problems, while mental health nurses (MHNs) seem not to be fully aware of these problems and the risk factors. Therefore, this study aims to develop supportive tools for MHNs regarding oral health to increase sensitization among MHNs and to provide MHNs with knowledge to recognize (potential) oral health problems in patients with a psychotic disorder. We used a human-centered design in which the user, MHNs as well as experts by experience, were placed in the centre of the research process. Problems and needs in MHNs working with patients with a psychotic disorder were addressed. To identify key issues of problem as well as the needs in terms of resources, we started with focus groups (n = 9). We analysed the data thematically based on context of patients and MHNs in practice regarding oral health, preferred oral health tools focused on MHN, and intended outcomes of tools. A Multi Criteria Decision Matrix was developed and analysed (n = 9) to identify the most optimal and viable solution based on established criteria and issues that are prevalent in the work of MHNs. Most promising result was the development of a brochure with an awareness screener. The brochure with awareness screener was developed as a low-fidelity prototype for MHNs regarding oral health in patients with a psychotic disorder, based on the latest scientific evidence. After testing it, the feasibility was tested through semi-structured interviews (n=19). MHNs and experts by experience were satisfied with the tool and provided recommendations for adjustments to the content. Significant augmentations to the brochure include a clinical lesson and a toothbrush with toothpaste for patients. We can conclude that a brochure with an awareness screener is feasible for MHNs. Future steps aiming to further refine and optimize care processes for oral health tools in MHNs, should take refining eligibility criteria for psychiatric populations and the language level of the target group of a tool into account.

Regenerative endodontic procedures (REPs) aim at recreating dental pulp tissue using biomaterials such as hydrogels. Their bioactivity is mostly linked to the nature of biomolecules or chemical compounds that will compose the endodontic hydrogel. However, many other parameters, such as hydrogel concentration, type, bioactive molecules solubility, of apex size were reported to influence the hydrogel behavior, leading to the inability to predict the clinical outcome. This lack of knowledge and the various parameters that should be considered, suggest that biological activity of endodontic hydrogel is impossible to anticipate and could hinder the bench to bedside transition. We formulated in this article our opinion that most of these parameters could be identified, described, and studied. A second part of the document lists some challenges and perspectives, including development of future mathematical models able to explain and predict the bioactivity of these endodontic hydrogel in clinic.

Asthma is a prevalent disease that around 300 million worldwide, resulting in substantial morbidity, mortality, and economic burden on a global scale. New clinical and laboratory research has shed light on the immunology causing asthma. Asthma is now recognized as a heterogeneous disease. A personalized medicine is based on the classification of asthma by endotype by linking observable characteristics to immunological mechanisms. Identifying endotype mechanisms is essential for better characterizing patients and personalizing therapeutic approaches with novel biological agents that target specific immune pathways. This article provides a summary of the major immunological mechanisms involved in the pathogenesis and emergence of the disease's phenotypic features, as well as the individualized treatment for severe asthma subtypes

Discrete distribution estimation is a fundamental statistical tool, which is widely used to perform data analysis tasks in various applications involving sensitive personal information. Due to privacy concerns, individuals may not always provide their raw information, which leads to unpredictable biases in the final results of estimated distribution. Local Differential Privacy (LDP) is an advanced technique for privacy protection of discrete distribution estimation. Currently, typical LDP mechanisms provide same protection for all items in the domain, which imposes unnecessary perturbation on less sensitive items and thus degrades the utility of final results. Although, several recent works try to alleviate this problem, the utility can be further improved. In this paper, we propose a novel notion called Item-Oriented Personalized LDP (IPLDP), which independently perturbs different items with different privacy budgets to achieve personalized privacy protection. Furthermore, to satisfy IPLDP, we propose the Item-Oriented Personalized Randomized Response (IPRR) based on the observation that the sensitivity of data shows an inverse relationship with the population size of respective individuals. Theoretical analysis and experimental results demonstrate that our method can provide fine-grained privacy protection and improve data utility simultaneously.

The study was conducted on applying machine learning and data mining methods to personalizing the treatment. This allows investigating individual patient characteristics. Personalization is built on the clustering method and associative rules. It was suggested to determine the average distance between instances for optimal performance metrics finding. The formalization of the medical data pre-processing stage for finding personalized solutions based on current standards and pharmaceutical protocols is proposed. The model of patient data is built. The paper presents the novel approach to clustering built on ensemble of cluster algorithm with better than k-means algorithm Hopkins metrics. The personalized treatment usually is based on decision tree. Such approach requires a lot of computation time and cannot be paralyzed. Therefore, it is proposed to classify persons by conditions, to determine deviations of parameters from the normative parameters of the group, as well as the average parameters. This made it possible to create a personalized approach to treatment for each patient based on long-term monitoring. According to the results of the analysis, it becomes possible to predict the optimal conditions for a particular patient and to find the medicaments treatment according to personal characteristics.