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Introduction: Cognitive reserve (CR) refers to the ability of the brain to cope with damage or pathology. In bipolar disorder (BD), it has been seen that the effects of the disease may potentially reduce CR, thus compromising cognitive outcomes. This concept takes on special relevance in late life in BD, due to the increased risk of cognitive decline because of the accumulative effects of the disease and the potential effects of aging. Therefore, we believe that CR may be a protective factor against cognitive decline in older adults with bipolar disorder (OABD). Objectives: The aim of this study was to study the CR in OABD compared with healthy controls (HC) and to analyze its association with psychosocial functioning and cognitive performance. Methods: A sample of euthymic OABD, defined as patients over 50 years old, and HC were included. CR was assessed using the CRASH scale. Differences in demographic, clinical, and cognitive variables between patients and HC were analyzed by t-test or X2 as appropriated. Lineal simple and multiple regressions analyses were used to study the association of CR and several clinical variables with functional and cognitive performance. Results: A total of 83 participants (42 OABD and 41 HC) were included. Compared to HC, OABD exhibited poorer cognitive performance (p<0.001), psychosocial functioning (p<0.001) and lower CR (p<0.001). Within the patient's group, the linear simple regression analysis revealed that CR was associated with psychosocial functioning (β=-2.16; p=0.037), attention (β= 3.03; p=0.005) and working memory (β = 2.98; p=0.005) while no clinical factors were associated. Age and CR were associated with processing speed and verbal memory, but after applying multiple regression model, only the effect of age remained significant (β =-2.26; p= 0.030, and β =-2.23; p= 0.032 respectively). CR, age, and number of episodes were related to visual memory, but the multiple regression showed that only age (β = -2.37; p= 0.023) and CR (β = 3.99; p<0.001) were associated. Regarding executive functions only the number of manic episodes were significant. CR and age at onset were associated with visuospatial ability, but multiple regression only showed association of CR (β =2.23; p=0.032). Other clinical factors such as number of depressive or hypomanic episodes, illness duration, admissions, type of BD, and psychotic symptoms were not associated. Conclusions: To the best of our knowledge, this is the first report that studies the CR in a sample of OABD. We demonstrated that OABD had lower CR than HC. Importantly, we observed that CR was associated with cognitive and psychosocial functioning in OABD, even more than disease-related factors. These results suggest the potential protector effect of CR against cognitive impairment, supporting that improving modifiable factors associated with the enhancement of CR can prevent cognitive decline. Disclosure of Interest: L. Montejo: None Declared, C. Torrent Grant / Research support from: Spanish Ministry of Science and Innovation (PI20/00344) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdireccion General de Evaluacio ́n and the Fondo Europeo de Desarrollo Regional (FEDER), S. Martín: None Declared, A. Ruiz: None Declared, M. Bort: None Declared, G. Fico Grant / Research support from: Fellowship from "La Caixa" Foundation (ID 100010434 - fellowship code LCF/BQ/DR21/11880019), V. Oliva: None Declared, M. De Prisco: None Declared, J. Sanchez-Moreno Grant / Research support from: Spanish Ministry of Science and Innovation (PI20/00060) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdireccion General de Evaluacio ́n and the Fondo Europeo de Desarrollo Regional (FEDER),, E. Jimenez Grant / Research support from: Spanish Ministry of Science and Innovation (PI20/00060)integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdireccion General de Evaluacio ́n and the Fondo Europeo de Desarrollo Regional (FEDER),, A. Martinez-Aran: None Declared, E. Vieta Grant / Research support from: Spanish Ministry of Science and Innovation (PI18/ 00805, PI21/00787) integrated into the Plan Nacional de I+D+I and cofinanced by the ISCIIISubdireccio ́n General de Evaluacio ́n and the Fondo Europeo de Desarrollo Regional (FEDER); the Instituto de Salud Carlos III; the CIBER of Mental Health (CIBERSAM); the Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement (2017 SGR 1365), the CERCA Programme, and the Departament de Salut de la Generalitat de Catalunya for the PERIS grant SLT006/17/00357; the European Union Horizon 2020 research and innovation program (EU.3.1.1. Understanding health, wellbeing and disease: Grant No 754907 and EU.3.1.3. Treating and managing disease: Grant No 945151)., B. Sole: None Declared [ABSTRACT FROM AUTHOR]

Introduction: Predicting acute affective episodes in individuals with Bipolar Disorder (BD) remains a clinical challenge. Specific environmental stressors, including air pollution, noise, and temperature variations might worsen affective symptoms or sleep in the general population, but their role in BD relapses is often overlooked. Indeed, they might exacerbate BD by perturbing circadian rhythms – fundamental aspects of BD. Objectives: We thereby present the protocol of this pilot study and future preliminary data. We aim to longitudinally assess sleep alterations, mood fluctuations, and environmental exposure to several factors (air pollutants, climate, noise, artificial light-at-night, green space access) in patients with BD and to check the association of these variables with BD relapses. Methods: In this pilot study, we will recruit 40 patients with BD in a 6-month prospective study. Patients were assessed during baseline, at 3 and 6 months. Data recollected will consist of a subjective (questionnaires) and objective (through meteorological stations) evaluation of physical environmental factors around the home residence; clinical assessment of mood and circadian rhythms, and continuous tracking of sleep-wake patterns, energy, and movement using actigraphy. Results: Expected results will show that exposure to a worse environment (higher pollution, noise, light exposure, climate) will be associated with worse BD outcomes (i.e., relapse, mood symptoms, sleep alterations). Conclusions: We will be sharing preliminary data from our ongoing study, offering insights into early patterns and findings that shed light on our objectives. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Introduction: In recent years, research has focused on the older adults with bipolar disorder (OABD), aged 50 years and over, a constantly growing population due to the increased of life expectancy. Actually, some authors suggest that these individuals constitute a distinct subtype with a specific and different needs such as seen in epidemiologic, clinical and cognitive features. Further research has revealed significant differences between females and males with BD in clinical and cognitive variables in middle-aged and young patients, but this topic among OABD population remains unclear. Objectives: The aim of this study is to identify the distinctive profile in clinical, functional and neurocognitive variables between females and males in OABD. Methods: A sample of OABD and Healthy Controls (HC) were included. Euthymic patients or in partial remission were included. Neurocognition was measured with a battery of tests that included premorbid intelligence quotient, working memory, verbal and visual memory, processing speed, language and executive functions. Independent t-test and Chi-squared test analysis were performed as appropriated. Results: According to the analysis, statistically significant differences were seen between females and males. A more impaired cognitive profile is observed in women. They performed worse in the subscales of Arithmetic (F= 6.728, p = <0.001), forward digits (F= 0.936, p = 0.019) and Total Digits (F= 1.208, p = 0.019) of the WAIS-III, in the Stroop Color Word Test, color reading (F= 0.130, p = < 0.001), in the Continuous Performance Test, block change measure (F= 2.059, p = 0.037), in the Rey-Osterrieth Complex Figure-copy (F= 0.005, p = 0.029) and in the Boston Naming Test (F= 0.011, p = 0.024). Nor significant differences were found in clinical neither in psychosocial functioning variables. Conclusions: In view of the following results, and since no differences were observed between women and men in terms of clinical and functional outcomes, it could be said that the differences observed in cognition cannot be explained by disease-related factors. Furthermore, these results highlight the need to develop a gender-specific cognitive interventions in OABD population. In this way, we could have an impact on the course of the illness to reach a better quality of life. Disclosure of Interest: S. Martín-Parra: None Declared, C. Torrent Grant / Research support from: Spanish Ministry of Science and Innovation (PI20/00344) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIIISubdireccion General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER), A. Ruiz: None Declared, M. Bort: None Declared, G. Fico Grant / Research support from: Fellowship from "La Caixa" Foundation (ID 100010434 - fellowship code LCF/BQ/DR21/11880019), V. Oliva: None Declared, M. Prisco: None Declared, J. Sanchez-Moreno Grant / Research support from: Spanish Ministry of Science and Innovation (PI20/00060) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdireccion General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER), E. Jimenez Grant / Research support from: Spanish Ministry of Science and Innovation (PI20/00060) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdireccion General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER), A. Martinez-Aran: None Declared, E. Vieta Grant / Research support from: Spanish Ministry of Science and Innovation (PI18/ 00805, PI21/00787) integrated into the Plan Nacional de I+D+I and cofinanced by the ISCIII Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER); the Instituto de Salud Carlos III; the CIBER of Mental Health (CIBERSAM); the Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement (2017 SGR 1365), the CERCA Programme, and the Departament de Salut de la Generalitat de Catalunya for the PERIS grant SLT006/17/00357; the European Union Horizon 2020 research and innovation program (EU.3.1.1. Understanding health, wellbeing and disease: Grant No 754907 and EU.3.1.3. Treating and managing disease: Grant No 945151), B. Sole: None Declared, L. Montejo: None Declared [ABSTRACT FROM AUTHOR]

Introduction: Bipolar disorder (BD) is a multifaceted illness encompassing mood, energy, cognitive and biorhythms alterations. Sleep disturbances are common in prodromic, acute and inter-episodic phases of BD. Suicidality presents a known association with sleep disturbances. However, their interplay in BD remains intricate and not fully elucidated. Objectives: The aim of the present systematic review (SR) and meta-analysis (MA) is to summarise the available evidence and to provide an estimate of the association between sleep disturbances and suicidality, defined as presence of suicide ideation, behaviour and suicide attempts, in patients with BD. Methods: We conducted a comprehensive literature search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines across PubMed, PsycINFO, and SCOPUS databases. We included all studies reporting an association between sleep problems and suicidal behaviour in BD patients. No language restriction was imposed. Effect sizes were calculated as odds ratio (OR) for dichotomic variables, standard mean difference (SMD) for continuous outcomes, and Spearman's coefficient (r) for correlations. Heterogeneity was assessed using the I2 statistic. Global inconsistency was evaluated using the Q statistics with the corresponding p-value. Results: The initial search yielded 911 unique abstracts, of which 62 underwent full-text screening. Fourteen publications were included, comprising twelve cross-sectional and two longitudinal studies. The total sample consisted of 19,601 subjects diagnosed with BD, of which 51.76% were females and 69.52% had a diagnosis of BD type 1. We found that people with BD and sleep disturbances tend to have higher suicidality, both current (SMD=0.79, 95%CI=0.53, 1.05) and lifetime (OR=1.8; 95%CI=1.41, 2.55), when compared with people with BD and no sleep disturbances. Additionally, patients with BD and a history of suicide attempts tend to have more sleep problems (OR=1.37, 95%CI=1.21, 1.55). Moreover, a positive correlation exists between suicidality and poor sleep quality measured by the Pittsburgh Sleep Quality Index (PSQI) (r= 0.24, 95%CI=0.10, 0.36). No heterogeneity was found, except in the subanalysis of correlation (I2=66.67%, Q p-value=0.01). Conclusions: Our SRMA outlines a positive relation between sleep disturbances and suicidality in patients with BD. The small number of included studies and the scarcity of longitudinal studies, preventing the inference of a causal relationship, represent the major limitations of this study. Also, studies with objective measures of sleep alterations are currently lacking. The prompt recognition, objective measurement, and treatment of sleep alterations could be crucial in averting or reducing suicidal attempts in BD. Disclosure of Interest: C. Possidente: None Declared, M. Bort: None Declared, M. De Prisco: None Declared, V. Oliva: None Declared, G. Fico Grant / Research support from: Fellowship from "La Caixa" Foundation (ID 100010434 - fellowship code LCF/BQ/DR21/11880019), L. Bracco: None Declared, C. Sommerhoff: None Declared, L. Montejo: None Declared, A. Murru Grant / Research support from: Spanish Ministry of Science and Innovation (PI19/00672, PI22/00840) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdireccion General de Evaluacio ́n and the Fondo Europeo de Desarrollo Regional (FEDER), E. Vieta Grant / Research support from: Spanish Ministry of Science and Innovation (PI18/ 00805, PI21/00787) integrated into the Plan Nacional de I+D+I and cofinanced by the ISCIII-Subdireccio ́n General de Evaluacio ́n and the Fondo Europeo de Desarrollo Regional (FEDER); the Instituto de Salud Carlos III; the CIBER of Mental Health (CIBERSAM); the Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement (2017 SGR 1365), the CERCA Programme, and the Departament de Salut de la Generalitat de Catalunya for the PERIS grant SLT006/17/00357; the European Union Horizon 2020 research and innovation program (EU.3.1.1. Understanding health, wellbeing and disease: Grant No 754907 and EU.3.1.3. Treating and managing disease: Grant No 945151). [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic had a great impact on mental health both in the general population and in individuals with preexisting mental disorders. Lockdown, social restrictions, changes in daily habits and limited access to health services led to changes in consultations in mental health services. This study aimed to determine changing trends in psychiatric admissions by the inclusion of adult patients admitted to the Emergency Department (ED) of Hospital Clínic of Barcelona between 2019 and 2021. Acute admissions, social issues and psychiatric diagnoses were compared between years, seasons and considering the interaction between both years and seasons. A total of 13,677 individuals were included in the analysis. An overall reduction in consultations to the ED and a higher proportion of acute admissions was observed in 2020 in context of the COVID-19 outbreak. Increased prevalence of sleeping disorders and substance use disorders was found in 2020. Self-harming behavior, suicidal thoughts and suicidal behavior showed an increasing tendency over time, with their highest rates in 2021. Prevention and management strategies should be considered in order to address increasing needs in mental health care., Competing Interests: Declaration of competing interest AGP has received CME-related honoraria, or consulting fees from Angelini, Janssen-Cilag, Casen Recordati, Rovi, LCN and Lundbeck. AF has received educational support from Janssen-Cilag, Lundbeck and Rovi. EV has received grants and served as consultant, advisor or CME speaker for the following entities: AB-Biotics, AbbVie, Adamed, Angelini, Biogen, Boehringer-Ingelheim, Celon Pharma, Compass, Dainippon Sumitomo Pharma, Ethypharm, Ferrer, Gedeon Richter, GH Research, Glaxo-Smith Kline, Janssen, Lundbeck, Medincell, Merck, Novartis, Orion Corporation, Organon, Otsuka, Roche, Rovi, Sage, Sanofi-Aventis, Sunovion, Takeda, and Viatris, outside the submitted work. MGR has received funding unrelated to the present work for research projects and/or honoraria as a consultant or speaker from the following entities: Angelini, Janssen, Lundbeck, Otsuka, ROVI, Sanofi-Aventis and Spanish Ministry of Science and Innovation- Instituto de Salud Carlos III. The rest of authors do not report any conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The prevalence of chronic diseases has shifted the burden of disease from incidental acute inpatient admissions to long-term coordinated care across healthcare institutions and the patient's home. Digital healthcare ecosystems emerge to target increasing healthcare costs and invest in standard Application Programming Interfaces (API), such as HL7 Fast Healthcare Interoperability Resources (HL7 FHIR) for trusted data flows., Objectives: This scoping review assessed the role and impact of HL7 FHIR and associated Implementation Guides (IGs) in digital healthcare ecosystems focusing on chronic disease management., Methods: To study trends and developments relevant to HL7 FHIR, a scoping review of the scientific and gray English literature from 2017 to 2023 was used., Results: The selection of 93 of 524 scientific papers reviewed in English indicates that the popularity of HL7 FHIR as a robust technical interface standard for the health sector has been steadily rising since its inception in 2010, reaching a peak in 2021. Digital Health applications use HL7 FHIR in cancer (45 %), cardiovascular disease (CVD) (more than 15 %), and diabetes (almost 15 %). The scoping review revealed that references to HL7 FHIR IGs are limited to ∼ 20 % of articles reviewed. HL7 FHIR R4 was most frequently referenced when the HL7 FHIR version was mentioned. In HL7 FHIR IGs registries and the internet, we found 35 HL7 FHIR IGs addressing chronic disease management, i.e., cancer (40 %), chronic disease management (25 %), and diabetes (20 %). HL7 FHIR IGs frequently complement the information in the article., Conclusions: HL7 FHIR matures with each revision of the standard as HL7 FHIR IGs are developed with validated data sets, common shared HL7 FHIR resources, and supporting tools. Referencing HL7 FHIR IGs cataloged in official registries and in scientific publications is recommended to advance data quality and facilitate mutual learning in growing digital healthcare ecosystems that nurture interoperability in digital health innovation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background : Bipolar disorder (BD) involves significant mood and energy shifts reflected in speech patterns. Detecting these patterns is crucial for diagnosis and monitoring, currently assessed subjectively. Advances in natural language processing offer opportunities to objectively analyze them. Aims : To (i) correlate speech features with manic-depressive symptom severity in BD, (ii) develop predictive models for diagnostic and treatment outcomes, and (iii) determine the most relevant speech features and tasks for these analyses. Methods : This naturalistic, observational study involved longitudinal audio recordings of BD patients at euthymia, during acute manic/depressive phases, and after-response. Patients participated in clinical evaluations, cognitive tasks, standard text readings, and storytelling. After automatic diarization and transcription, speech features, including acoustics, content, formal aspects, and emotionality, will be extracted. Statistical analyses will (i) correlate speech features with clinical scales, (ii) use lasso logistic regression to develop predictive models, and (iii) identify relevant speech features. Results : Audio recordings from 76 patients (24 manic, 21 depressed, 31 euthymic) were collected. The mean age was 46.0 ± 14.4 years, with 63.2% female. The mean YMRS score for manic patients was 22.9 ± 7.1, reducing to 5.3 ± 5.3 post-response. Depressed patients had a mean HDRS-17 score of 17.1 ± 4.4, decreasing to 3.3 ± 2.8 post-response. Euthymic patients had mean YMRS and HDRS-17 scores of 0.97 ± 1.4 and 3.9 ± 2.9, respectively. Following data pre-processing, including noise reduction and feature extraction, comprehensive statistical analyses will be conducted to explore correlations and develop predictive models. Conclusions : Automated speech analysis in BD could provide objective markers for psychopathological alterations, improving diagnosis, monitoring, and response prediction. This technology could identify subtle alterations, signaling early signs of relapse. Establishing standardized protocols is crucial for creating a global speech cohort, fostering collaboration, and advancing BD understanding.

Background: The ethnobotanical analysis of two bordering areas allows for the in-depth understanding of the dynamics of Local Ecological Knowledge, which mirrors the naturalistic, historical, and sociopolitical features of each area. As part of the Interreg Italy-Switzerland B-ICE&Heritage and GEMME projects, this work is an ethnobotanical comparative study of two neighboring Alpine territories: Valmalenco (Italy) and Valposchiavo (Switzerland)., Methods: A total of 471 informants were interviewed on different fields of use (medicinal, food, veterinary, etc.). All data were organized in Excel™ spreadsheets. Informant Consensus Factor was calculated for the pathologies reported. Jaccard's similarity indices were calculated to compare the Valmalenco and Valposchiavo areas. Subsequently, another comparison between Valmalenco/Valposchiavo and Italian/Swiss Alpine neighboring areas was carried out., Results: The number of taxa for Valmalenco was 227 (77 families) and 226 in Valposchiavo (65). Out of the 10 most cited species, 7 were mentioned in both. Arnica montana L. was the most cited in Valmalenco, and Sambucus nigra L. in Valposchiavo. The 5 most cited families were the same. Regarding the medicinal and food fields, the similarity indices were fairly low (0.31 and 0.34 for the species; 0.22 and 0.31 for the uses). Concerning the comparison with Italian and Swiss Alps, similarity values were slightly higher with Italy (Valmalenco food species: 0.38 with Italy and 0.26 with Switzerland, medicinal: 0.26 IT and 0.14 SW; Valposchiavo food species: 0.36 with IT and 0.26 with SW, medicinal: 0.21 IT and 0.14 SW)., Conclusion: Although Valmalenco and Valposchiavo partly share natural environment, language, history, and culture, they had low similarity indices. They both seemed to have more similarities with Italy than Switzerland, maintaining low values with the surrounding territories too. They showed a common core of Local Ecological Knowledge with several divergent branches possibly due to pivotal historical happenings, as well as more modern external influences., (© 2024. The Author(s).)

Background: Bipolar disorder is highly prevalent and consists of biphasic recurrent mood episodes of mania and depression, which translate into altered mood, sleep and activity alongside their physiological expressions., Aims: The IdenTifying dIgital bioMarkers of illnEss activity and treatment response in BipolAr diSordEr with a novel wearable device (TIMEBASE) project aims to identify digital biomarkers of illness activity and treatment response in bipolar disorder., Method: We designed a longitudinal observational study including 84 individuals. Group A comprises people with acute episode of mania ( n = 12), depression ( n = 12 with bipolar disorder and n = 12 with major depressive disorder (MDD)) and bipolar disorder with mixed features ( n = 12). Physiological data will be recorded during 48 h with a research-grade wearable (Empatica E4) across four consecutive time points (acute, response, remission and episode recovery). Group B comprises 12 people with euthymic bipolar disorder and 12 with MDD, and group C comprises 12 healthy controls who will be recorded cross-sectionally. Psychopathological symptoms, disease severity, functioning and physical activity will be assessed with standardised psychometric scales. Physiological data will include acceleration, temperature, blood volume pulse, heart rate and electrodermal activity. Machine learning models will be developed to link physiological data to illness activity and treatment response. Generalisation performance will be tested in data from unseen patients., Results: Recruitment is ongoing., Conclusions: This project should contribute to understanding the pathophysiology of affective disorders. The potential digital biomarkers of illness activity and treatment response in bipolar disorder could be implemented in a real-world clinical setting for clinical monitoring and identification of prodromal symptoms. This would allow early intervention and prevention of affective relapses, as well as personalisation of treatment.

The impact of air pollution and climate change on mental health has recently raised strong concerns. However, a comprehensive overview analyzing the existing evidence while addressing relevant biases is lacking. This umbrella review systematically searched the PubMed/Medline, Scopus and PsycINFO databases (up to June 26, 2023) for any systematic review with meta-analysis investigating the association of air pollution or climate change with mental health outcomes. We used the R metaumbrella package to calculate and stratify the credibility of the evidence according to criteria (i.e., convincing, highly suggestive, suggestive, or weak) that address several biases, complemented by sensitivity analyses. We included 32 systematic reviews with meta-analysis that examined 284 individual studies and 237 associations of exposures to air pollution or climate change hazards and mental health outcomes. Most associations (n=195, 82.3%) involved air pollution, while the rest (n=42, 17.7%) regarded climate change hazards (mostly focusing on temperature: n=35, 14.8%). Mental health outcomes in most associations (n=185, 78.1%) involved mental disorders, followed by suicidal behavior (n=29, 12.4%), access to mental health care services (n=9, 3.7%), mental disorders-related symptomatology (n=8, 3.3%), and multiple categories together (n=6, 2.5%). Twelve associations (5.0%) achieved convincing (class I) or highly suggestive (class II) evidence. Regarding exposures to air pollution, there was convincing (class I) evidence for the association between long-term exposure to solvents and a higher incidence of dementia or cognitive impairment (odds ratio, OR=1.139), and highly suggestive (class II) evidence for the association between long-term exposure to some pollutants and higher risk for cognitive disorders (higher incidence of dementia with high vs. low levels of carbon monoxide, CO: OR=1.587; higher incidence of vascular dementia per 1 μg/m 3 increase of nitrogen oxides, NO x : hazard ratio, HR=1.004). There was also highly suggestive (class II) evidence for the association between exposure to airborne particulate matter with diameter ≤10 μm (PM 10 ) during the second trimester of pregnancy and the incidence of post-partum depression (OR=1.023 per 1 μg/m 3 increase); and for the association between short-term exposure to sulfur dioxide (SO 2 ) and schizophrenia relapse (risk ratio, RR=1.005 and 1.004 per 1 μg/m 3 increase, respectively 5 and 7 days after exposure). Regarding climate change hazards, there was highly suggestive (class II) evidence for the association between short-term exposure to increased temperature and suicide- or mental disorders-related mortality (RR=1.024), suicidal behavior (RR=1.012), and hospital access (i.e., hospitalization or emergency department visits) due to suicidal behavior or mental disorders (RR=1.011) or mental disorders only (RR=1.009) (RR values per 1°C increase). There was also highly suggestive (class II) evidence for the association between short-term exposure to increased apparent temperature (i.e., the temperature equivalent perceived by humans) and suicidal behavior (RR=1.01 per 1°C increase). Finally, there was highly suggestive (class II) evidence for the association between the temporal proximity of cyclone exposure and severity of symptoms of post-traumatic stress disorder (r=0.275). Although most of the above associations were small in magnitude, they extend to the entire world population, and are therefore likely to have a substantial impact. This umbrella review classifies and quantifies for the first time the global negative impacts that air pollution and climate change can exert on mental health, identifying evidence-based targets that can inform future research and population health actions., (© 2024 World Psychiatric Association.)

Khat leaves, indigenous to eastern Africa, have been chewed for centuries for their stimulant effects, attributed to alkaloids such as cathinone and cathine. Although associated with gastric disorders like gastritis and gastro-oesophageal reflux disease, the underlying molecular mechanisms remain unclear. This study aimed to examine the morpho-anatomy of khat leaves using light microscopy and histochemistry and to assess the effects of leaf extracts and alkaloids on human gastric epithelial cells (GES-1). The study identified specific cells in the palisade-spongy transition zone as storage sites for psychoactive alkaloids. Leaf extracts were prepared by mimicking the chewing process, including a prolonged salivary phase followed by a gastric phase. Cytotoxicity and cell viability were evaluated using LDH and MTT assays, respectively. Additionally, the impact on IL-8 secretion, a key chemokine in gastric inflammation, was analysed under normal and TNF-α-stimulated conditions. The results showed no increase in cytotoxicity up to 250 µg/mL. However, there was a significant decrease in cell metabolism and a reduction in both basal and TNF-α-induced IL-8 secretion, but cathinone and cathine were inactive. These findings suggest that khat may not directly cause the gastric issues reported in the literature, which would rather be attributed to other confounding factors, highlighting the need for further research to clarify its biological impacts.

Over the last six decades, lithium has been considered the gold standard treatment for the long-term management of bipolar disorder due to its efficacy in preventing both manic and depressive episodes as well as suicidal behaviors. Nevertheless, despite numerous observed effects on various cellular pathways and biologic systems, the precise mechanism through which lithium stabilizes mood remains elusive. Furthermore, there is recent support for the therapeutic potential of lithium in other brain diseases. This review offers a comprehensive examination of contemporary understanding and predominant theories concerning the diverse mechanisms underlying lithium's effects. These findings are based on investigations utilizing cellular and animal models of neurodegenerative and psychiatric disorders. Recent studies have provided additional support for the significance of glycogen synthase kinase-3 (GSK3) inhibition as a crucial mechanism. Furthermore, research has shed more light on the interconnections between GSK3-mediated neuroprotective, antioxidant, and neuroplasticity processes. Moreover, recent advancements in animal and human models have provided valuable insights into how lithium-induced modifications at the homeostatic synaptic plasticity level may play a pivotal role in its clinical effectiveness. We focused on findings from translational studies suggesting that lithium may interface with microRNA expression. Finally, we are exploring the repurposing potential of lithium beyond bipolar disorder. These recent findings on the therapeutic mechanisms of lithium have provided important clues toward developing predictive models of response to lithium treatment and identifying new biologic targets. SIGNIFICANCE STATEMENT: Lithium is the drug of choice for the treatment of bipolar disorder, but its mechanism of action in stabilizing mood remains elusive. This review presents the latest evidence on lithium's various mechanisms of action. Recent evidence has strengthened glycogen synthase kinase-3 (GSK3) inhibition, changes at the level of homeostatic synaptic plasticity, and regulation of microRNA expression as key mechanisms, providing an intriguing perspective that may help bridge the mechanistic gap between molecular functions and its clinical efficacy as a mood stabilizer., Competing Interests: E.V. has received grants and served as consultant, advisor, or CME speaker for the following entities: AB-Biotics, AbbVie, Angelini, Biogen, Biohaven, Boehringer-Ingelheim, Celon Pharma, Compass, Dainippon Sumitomo Pharma, Ethypharm, Ferrer, Gedeon Richter, GH Research, Glaxo-Smith Kline, Idorsia, Janssen, Lundbeck, Medincell, Novartis, Orion Corporation, Organon, Otsuka, Rovi, Sage, Sanofi-Aventis, Sunovion, Takeda, and Viatris outside the submitted work. G.F. has received CME-related honoraria or consulting fees from Angelini, Janssen-Cilag, and Lundbeck, Abbot. A.B. has received grants and served as a consultant for miCure Therapeutics. The other authors do not have an actual or perceived conflict of interest with the contents of this article., (U.S. Government work not protected by U.S. copyright.)

Background: Healthy lifestyle interventions have a positive impact on multiple disease trajectories, including cancer-related outcomes. Specifically, appropriate habitual physical activity, adequate sleep, and a regular wholesome diet are of paramount importance for the wellness and supportive care of survivors of cancer. Mobile health (mHealth) apps have the potential to support novel tailored lifestyle interventions., Objective: This observational pilot study aims to assess the feasibility of mHealth multidimensional longitudinal monitoring in survivors of cancer. The primary objective is to test the compliance (user engagement) with the monitoring solution. Secondary objectives include recording clinically relevant subjective and objective measures collected through the digital solution., Methods: This is a monocentric pilot study taking place in Bangor, Wales, United Kingdom. We plan to enroll up to 100 adult survivors of cancer not receiving toxic anticancer treatment, who will provide self-reported behavioral data recorded via a dedicated app and validated questionnaires and objective data automatically collected by a paired smartwatch over 16 weeks. The participants will continue with their normal routine surveillance care for their cancer. The primary end point is feasibility (eg, mHealth monitoring acceptability). Composite secondary end points include clinically relevant patient-reported outcome measures (eg, the Edmonton Symptom Assessment System score) and objective physiological measures (eg, step counts). This trial received a favorable ethical review in May 2023 (Integrated Research Application System 301068)., Results: This study is part of an array of pilots within a European Union funded project, entitled "GATEKEEPER," conducted at different sites across Europe and covering various chronic diseases. Study accrual is anticipated to commence in January 2024 and continue until June 2024. It is hypothesized that mHealth monitoring will be feasible in survivors of cancer; specifically, at least 50% (50/100) of the participants will engage with the app at least once a week in 8 of the 16 study weeks., Conclusions: In a population with potentially complex clinical needs, this pilot study will test the feasibility of multidimensional remote monitoring of patient-reported outcomes and physiological parameters. Satisfactory compliance with the use of the app and smartwatch, whether confirmed or infirmed through this study, will be propaedeutic to the development of innovative mHealth interventions in survivors of cancer., International Registered Report Identifier (irrid): PRR1-10.2196/52957., (©Pasquale F Innominato, Jamie H Macdonald, Wendy Saxton, Laura Longshaw, Rachel Granger, Iman Naja, Carlo Allocca, Ruth Edwards, Solah Rasheed, Frans Folkvord, Jordi de Batlle, Rohit Ail, Enrico Motta, Catherine Bale, Claire Fuller, Anna P Mullard, Christian P Subbe, Dawn Griffiths, Nicholas I Wreglesworth, Leandro Pecchia, Giuseppe Fico, Alessio Antonini. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 30.04.2024.)

This paper examines the ethical and legal challenges encountered during the GATEKEEPER Project and how these challenges informed the development of a comprehensive framework for future Large-Scale Pilot (LSP) projects. GATEKEEPER is a LSP Project with 48 partners conducting 30 implementation studies across Europe with 50,000 target participants grouped into 9 Reference Use Cases. The project underscored the complexity of obtaining ethical approval across various jurisdictions with divergent regulations and procedures. Through a detailed analysis of the issues faced and the strategies employed to navigate these challenges, this study proposes an ethical and legal framework. This framework, derived from a comparative analysis of ethical application forms and regulations, aims to streamline the ethical approval process for future LSP research projects. By addressing the hurdles encountered in GATEKEEPER, the proposed framework offers a roadmap for more efficient and effective project management, ensuring smoother implementation of similar projects in the future., (© 2024. The Author(s).)

Obsessive-compulsive disorder (OCD) frequently co-occurs with various psychiatric conditions and may impact as many as one-fifth of individuals diagnosed with bipolar disorder (BD). Despite the expanding body of literature on the coexistence of OCD and BD, there is a notable lack of comprehensive data pertaining to the distinct features of obsessive-compulsive symptoms that define this comorbidity. To bridge this knowledge gap, we conducted a systematic search of PubMed/MEDLINE, Scopus, EMBASE, and PsycINFO until August 7th, 2023. We performed random-effects meta-analyses to compare individuals with both OCD and BD to those with OCD in terms of OCD symptomatology as well as the specific categories of obsessions and compulsions. Out of the 10,393 records initially screened, 17 studies were ultimately incorporated into the qualitative assessment, with 15 of them being included in the quantitative analysis. Individuals with OCD and BD experienced fewer lifetime contamination obsessions (OR=0.71; 95 %CI=0.53, 0.95; p = 0.021) and more sexual obsessions (OR=1.77; 95 %CI=1.03, 3.04; p = 0.04) compared to individuals with OCD without BD. No significant difference was observed for other types of obsessions or compulsions or for the severity of OCD symptoms, although BD type may play a role according to meta-regression analyses. The detection of the presence of sexual or contamination obsessions through a detailed interview may be the focus of clinical attention when assessing OCD in the context of comorbid BD. Sub-phenotyping complex clinical presentation of comorbid psychiatric disorders can aid in making more informed decisions when choosing an appropriate treatment approach., Competing Interests: Declaration of Competing Interest EV has received grants and served as consultant, advisor, or CME speaker for the following entities: AB-Biotics, AbbVie, Angelini, Biogen, Biohaven, Boehringer-Ingelheim, Celon Pharma, Compass, Dainippon Sumitomo Pharma, Ethypharm, Ferrer, Gedeon Richter, GH Research, Glaxo-Smith Kline, Idorsia, Janssen, Lundbeck, Medincell, Novartis, Orion Corporation, Organon, Otsuka, Rovi, Sage, Sanofi-Aventis, Sunovion, Takeda, and Viatris, outside the submitted work; GF has received CME-related honoraria, or consulting fees from Angelini, Janssen-Cilag and Lundbeck; GF's work is supported by a fellowship from "La Caixa" Foundation (ID 100010434 fellowship code LCF/BQ/DR21/11880019). All other authors have no conflicts to declare., (Copyright © 2023. Published by Elsevier B.V.)

Background: There are no recommendations based on the efficacy of specific drugs for the treatment of psychotic depression. To address this evidence gap, we did a network meta-analysis to assess and compare the efficacy and safety of pharmacological treatments for psychotic depression., Methods: In this systematic review and network meta-analysis, we searched ClinicalTrials.gov, CENTRAL, Embase, PsycINFO, PubMed, Scopus, and Web of Science from inception to Nov 23, 2023 for randomised controlled trials published in any language that assessed pharmacological treatments for individuals of any age with a diagnosis of a major depressive episode with psychotic features, in the context of major depressive disorder or bipolar disorder in any setting. We excluded continuation or maintenance trials. We screened the study titles and abstracts identified, and we extracted data from relevant studies after full-text review. If full data were not available, we requested data from study authors twice. We analysed treatments for individual drugs (or drug combinations) and by grouping them on the basis of mechanisms of action. The primary outcomes were response rate (ie, the proportion of participants who responded to treatment) and acceptability (ie, the proportion who discontinued treatment for any reason). We calculated risk ratios and did separate frequentist network meta-analyses by using random-effects models. The risk of bias of individual studies was assessed with the Cochrane risk-of-bias tool and the confidence in the evidence with the Confidence-In-Network-Meta-Analysis (CINeMA). This study was registered with PROSPERO, CRD42023392926., Findings: Of 6313 reports identified, 16 randomised controlled trials were included in the systematic review, and 14 were included in the network meta-analyses. The 16 trials included 1161 people with psychotic depression (mean age 50·5 years [SD 11·4]). 516 (44·4%) participants were female and 422 (36·3%) were male; sex data were not available for the other 223 (19·2%). 489 (42·1%) participants were White, 47 (4·0%) were African American, and 12 (1·0%) were Asian; race or ethnicity data were not available for the other 613 (52·8%). Only the combination of fluoxetine plus olanzapine was associated with a higher proportion of participants with a treatment response compared with placebo (risk ratio 1·91 [95% CI 1·27-2·85]), with no differences in terms of safety outcomes compared with placebo. When treatments were grouped by mechanism of action, the combination of a selective serotonin reuptake inhibitor with a second-generation antipsychotic was associated with a higher proportion of treatment responses than was placebo (1·89 [1·17-3·04]), with no differences in terms of safety outcomes. In head-to-head comparisons of active treatments, a significantly higher proportion of participants had a response to amitriptyline plus perphenazine (3·61 [1·23-10·56]) and amoxapine (3·14 [1·01-9·80]) than to perphenazine, and to fluoxetine plus olanzapine compared with olanzapine alone (1·60 [1·09-2·34]). Venlafaxine, venlafaxine plus quetiapine (2·25 [1·09-4·63]), and imipramine (1·95 [1·01-3·79]) were also associated with a higher proportion of treatment responses overall. In head-to-head comparisons grouped by mechanism of action, antipsychotic plus antidepressant combinations consistently outperformed monotherapies from either drug class in terms of the proportion of participants with treatment responses. Heterogeneity was low. No high-risk instances were identified in the bias assessment for our primary outcomes., Interpretation: According to the available evidence, the combination of a selective serotonin reuptake inhibitor and a second-generation antipsychotic-and particularly of fluoxetine and olanzapine-could be the optimal treatment choice for psychotic depression. These findings should be taken into account in the development of clinical practice guidelines. However, these conclusions should be interpreted cautiously in view of the low number of included studies and the limitations of these studies., Funding: None., Competing Interests: Declaration of interests GA has received honoraria for continuing medical education (CME) or consulting fees from Angelini, Casen Recordati, Janssen-Cilag, Lundbeck, Otsuka, and Rovi. AM has received grants and served as a paid consultant, adviser or CME speaker for Angelini, Idorsia, Janssen, Lundbeck, and Sanofi-Aventis. AdB has received grants and served as a paid consultant, adviser, or CME speaker for Angelini, Lundbeck, Newron, Otsuka, and Viatris. MS has received honoraria or been a consultant for AbbVie, Angelini, Lundbeck, and Otsuka. EV has received grants and served as a paid consultant, adviser, or CME speaker for AB-Biotics, Abbott, AbbVie, Adamed, Angelini, Biogen, Biohaven, Boehringer Ingelheim, Cambridge University Press, Casen-Recordati, Celon, Compass, Dainippon Sumitomo, Elsevier, Ethypharm, Ferrer, Galenica, Gedeon Richter, GH Research, GlaxoSmithKline, Janssen, Lundbeck, Medincell, Merck, Novartis, Oxford University Press, Orion, Organon, Otsuka, Roche, Rovi, Sage, Sanofi-Aventis, Sunovion, Takeda, and Viatris. AS has received consultation fees from Taliaz. CF has received speaker fees from Janssen. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: : To explore illness-related factors in patients with major depressive disorder (MDD) recipients of adjunctive minocycline (200 mg/day) treatment. The analysis included participants experiencing MDD from a 12-week, double blind, placebo-controlled, randomized clinical trial (RCT)., Methods: : This is a sub-analysis of a RCT of all 71 participants who took part in the trial. The impact of illness chronicity (illness duration and number of depressive episodes), systemic illness (endocrine, cardiovascular and obesity), adverse effects and minocycline were evaluated as change from baseline to endpoint (12-week) using ANCOVA., Results: : There was a consistent but statistically non-significant trend on all outcomes in favour of the use of adjunctive minocycline for participants without systemic illness, less illness chronicity, and fewer adverse effects., Conclusion: : Understanding the relationship between MDD and illness chronicity, comorbid systemic illness, and adverse effects, can potentially better characterise those individuals who are more likely to respond to adjunctive anti-inflammatory medications.

This study delves into the ethnoveterinary medicine (EVM) practiced by pastoralists along the transhumance routes in southwestern Angola. Within the framework of three cooperation projects, we conducted 434 interviews, collecting information on 89 taxa used for treating 16 livestock diseases. The most cited species was Ptaeroxylon obliquum (132 citations), followed by Salvadora persica (59) and Elaeodendron transvaalense (49). Contagious bovine pleuropneumonia (CBPP) was the disease most cited (223 citations; 44 species), followed by wounds (95; 20) and Newcastle (86; 14). We found that 30 species and 48 uses have not been previously reported in the ethnoveterinary literature. Jaccard index (mean value = 0.13) showed a greatly diversified knowledge among the ethnic groups: Kuvale and Nyaneka were the most knowledgeable and should be included in the various strategies for disseminating EVM in the area. Most informants recognized that abundance of some species decreased in the last years as a result of human activities and climatic changes. Finally, we discuss challenges in preserving the EVM in the area. Our findings suggest that preservation of the EVM in southwestern Angola is widely impacted by the access to biomedicine. Future studies should investigate the opportunity to integrate traditional medicine into mainstream development projects, which is crucial for decolonizing the veterinary sector in Angola.

(1) Background: Within the framework of the European Interreg Italy-Switzerland B-ICE & Heritage project (2018-2022), this study originated from a three-year ethnobotanical survey in Valmalenco (Sondrio, Italy). Following a preliminary work published by our group, this research further explored the folk therapeutic use of Achillea erba-rotta subsp. moschata (Wulfen) I.Richardson (Asteraceae) for dyspepsia disorders, specifically its anti-inflammatory potential at a gastrointestinal level. (2) Methods: Semi-structured interviews were performed. The bitter taste was investigated through molecular docking software (PLANTS, GOLD), while the anti-inflammatory activity of the hydroethanolic extract, infusion, and decoction was evaluated based on the release of IL-8 and IL-6 after treatment with TNFα or Helicobacter pylori . The minimum inhibitory concentration and bacterial adhesion on the gastric epithelium were evaluated. (3) Results: In total, 401 respondents were interviewed. Molecular docking highlighted di-caffeoylquinic acids as the main compounds responsible for the interaction with bitter taste receptors. The moderate inhibition of IL-6 and IL-8 release was recorded, while, in the co-culture with H. pylori , stronger anti-inflammatory potential was expressed (29-45 μg/mL). The concentration-dependent inhibition of H. pylori growth was recorded (MIC = 100 μg/mL), with a significant anti-adhesive effect. (4) Conclusions: Confirming the folk tradition, the study emphasizes the species' potentiality for dyspepsia disorders. Future studies are needed to identify the components mostly responsible for the biological effects.

The COVID-19 pandemic, a period of great turmoil, was coupled with the emergence of an "infodemic", a state when the public was bombarded with vast amounts of unverified information from dubious sources that led to a chaotic information landscape. The excessive flow of messages to citizens, combined with the justified fear and uncertainty imposed by the unknown virus, cast a shadow on the credibility of even well-intentioned sources and affected the emotional state of the public. Several studies highlighted the mental toll this environment took on citizens by analyzing their discourse on online social networks (OSNs). In this study, we focus on the activity of prominent pharmaceutical companies on Twitter, currently known as X, as well as the public's response during the COVID-19 pandemic. Communication between companies and users is examined and compared in two discrete channels, the COVID-19 and the non-COVID-19 channel, based on the content of the posts circulated in them in the period between March 2020 and September 2022, while the emotional profile of the content is outlined through a state-of-the-art emotion analysis model. Our findings indicate significantly increased activity in the COVID-19 channel compared to the non-COVID-19 channel while the predominant emotion in both channels is joy. However, the COVID-19 channel exhibited an upward trend in the circulation of fear by the public. The quotes and replies produced by the users, with a stark presence of negative charge and diffusion indicators, reveal the public's preference for promoting tweets conveying an emotional charge, such as fear, surprise, and joy. The findings of this research study can inform the development of communication strategies based on emotion-aware messages in future crises.

A better understanding of patients' adherence to treatment is a prerequisite to maximize the benefit of healthcare provision for patients, reduce treatment costs, and is a key factor in a variety of subsequent health outcomes. We aim to understand the state of the art of scientific evidence about which factors influence patients' adherence to treatment. A systematic literature review was conducted using PRISMA guidelines in five separate electronic databases of scientific publications: PubMed, PsycINFO (ProQuest), Cochrane library (Ovid), Google Scholar, and Web of Science. The search focused on literature reporting the significance of factors in adherence to treatment between 2011 and 2021, including only experimental studies (e.g., randomized controlled trials [RCT], clinical trials, etc.). We included 47 experimental studies. The results of the systematic review (SR) are grouped according to predetermined categories of the World Health Organization (WHO): socioeconomic, treatment, condition, personal, and healthcare-related factors. This review gives an actual overview of evidence-based studies on adherence and analyzed the significance of factors defined by the WHO classification. By showing the strength of certain factors in several independent studies and concomitantly uncovering gaps in research, these insights could serve as a basis for the design of future adherence studies and models., (© 2024 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

Objectives: To understand treatment practices for bipolar disorders (BD), this study leveraged the Global Bipolar Cohort collaborative network to investigate pharmacotherapeutic treatment patterns in multiple cohorts of well-characterized individuals with BD in North America, Europe, and Australia., Methods: Data on pharmacotherapy, demographics, diagnostic subtypes, and comorbidities were provided from each participating cohort. Individual site and regional pooled proportional meta-analyses with generalized linear mixed methods were conducted to identify prescription patterns., Results: This study included 10,351 individuals from North America (n = 3985), Europe (n = 3822), and Australia (n = 2544). Overall, participants were predominantly female (60%) with BD-I (60%; vs. BD-II = 33%). Cross-sectionally, mood-stabilizing anticonvulsants (44%), second-generation antipsychotics (42%), and antidepressants (38%) were the most prescribed medications. Lithium was prescribed in 29% of patients, primarily in the Australian (31%) and European (36%) cohorts. First-generation antipsychotics were prescribed in 24% of the European versus 1% in the North American cohort. Antidepressant prescription rates were higher in BD-II (47%) compared to BD-I (35%). Major limitations were significant differences among cohorts based on inclusion/exclusion criteria, data source, and time/year of enrollment into cohort., Conclusions: Mood-stabilizing anticonvulsants, second-generation antipsychotics, and antidepressants were the most prescribed medications suggesting prescription patterns that are not necessarily guideline concordant. Significant differences exist in the prescription practices across different geographic regions, especially the underutilization of lithium in the North American cohorts and the higher utilization of first-generation antipsychotics in the European cohorts. There is a need to conduct future longitudinal studies to further explore these differences and their impact on outcomes, and to inform and implement evidence-based guidelines to help improve treatment practices in BD., (© 2023 The Authors. Bipolar Disorders published by John Wiley & Sons Ltd.)

The European Project GATEKEEPER aims to develop a platform and marketplace to ensure a healthier independent life for the aging population. In this platform the role of HL7 FHIR is to provide a shared logical data model to collect data in heterogeneous living, which can be used by AI Service and the Gatekeeper HL7 FHIR Implementation Guide was created for this purpose. Independent pilots used this IG and illustrate the impact of the approach, benefit, value, and scalability.

Background: Bipolar disorder (BD) lacks objective measures for illness activity and treatment response. Electrodermal activity (EDA) is a quantitative measure of autonomic function, which is altered in manic and depressive episodes. We aimed to explore differences in EDA (1) inter-individually: between patients with BD on acute mood episodes, euthymic states and healthy controls (HC), and (2) intra-individually: longitudinally within patients during acute mood episodes of BD and after clinical remission., Methods: A longitudinal observational study. EDA was recorded using a research-grade wearable in patients with BD during acute manic and depressive episodes and at clinical remission. Euthymic BD patients and HC were recorded during a single session. We compared EDA parameters derived from the tonic (mean EDA, mEDA) and phasic components (EDA peaks per minute, pmEDA, and EDA peaks mean amplitude, pmaEDA). Inter- and intra-individual comparisons were computed respectively with ANOVA and paired t-tests., Results: 49 patients with BD (15 manic, 9 depressed, and 25 euthymic), and 19 HC were included. Patients with bipolar depression showed significantly reduced mEDA (p = 0.003) and pmEDA (p = 0.001), which increased to levels similar to euthymia or HC after clinical remission (mEDA, p = 0.011; pmEDA, p < 0.001; pmaEDA, p < 0.001). Manic patients showed no differences compared to euthymic patients and HCs, but a significant reduction of tonic and phasic EDA parameters after clinical remission (mEDA, p = 0.035; pmEDA, p = 0.004)., Limitations: Limited sample size, high inter-individual variability of EDA parameters, limited comparability to previous studies and non-adjustment for medication., Conclusion: EDA ecological monitoring might provide several opportunities for early detection of depressive symptoms, and might aid at assessing early response to treatments in mania and bipolar depression., Competing Interests: Declaration of competing interest GA has received CME-related honoraria, or consulting fees from Janssen-Cilag, Lundbeck, Lundbeck/Otsuka, Rovi, Casen Recordati, and Angelini, with no financial or other relationship relevant to the subject of this article. IP has received CME-related honoraria, or consulting fees from ADAMED, Janssen-Cilag, and Lundbeck. IG has received grants and served as consultant, advisor or CME speaker for the following identities: Angelini, Casen Recordati, Ferrer, Janssen Cilag, and Lundbeck, Lundbeck-Otsuka, Luye, SEI Healthcare. IG has received grants and served as consultant, advisor or CME speaker for the following identities: Angelini, Casen Recordati, Ferrer, Janssen Cilag, and Lundbeck, Lundbeck-Otsuka, Luye, SEI Healthcare. AGP has received CME-related honoraria, or consulting fees from Janssen-Cilag, Lundbeck, Casen Recordati, LCN and Angelini. GF has received CME-related honoraria, or consulting fees from Angelini, Janssen-Cilag and Lundbeck; GF's work is supported by a fellowship from “La Caixa” Foundation (ID 100010434 fellowship code LCF/BQ/DR21/11880019). AHY has received honoraria for lectures and advisory boards for all major pharmaceutical companies with drugs used in affective and related disorders. EV has received grants and served as consultant, advisor, or CME speaker for the following entities: AB-Biotics, AbbVie, Angelini, Biogen, Biohaven, Boehringer-Ingelheim, Celon Pharma, Compass, Dainippon Sumitomo Pharma, Ethypharm, Ferrer, Gedeon Richter, GH Research, Glaxo-Smith Kline, Idorsia, Janssen, Lundbeck, Medincell, Novartis, Orion Corporation, Organon, Otsuka, Rovi, Sage, Sanofi-Aventis, Sunovion, Takeda, and Viatris, outside the submitted work; DHM has received CME-related honoraria and served as consultant for Abbott, Angelini, Ethypharm Digital Therapy and Janssen-Cilag. All authors report no financial or other relationship relevant to the subject of this article., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In this work, we studied Tanacetum vulgare , Tanacetum parthenium , and Tanacetum corymbosum (Asteraceae) cultivated at the Ghirardi Botanic Garden (Toscolano Maderno, Brescia, Northern Italy) of the University of Milan. An integrative research approach was adopted: microscopic and histochemical, with special focus on the secretory structures responsible for the productivity of secondary metabolites; phytochemical, with the analysis of the essential oil (EO) profiles from the air-dried, flowered aerial parts collected in June 2021; bio-ecological, with emphasis, based on literature data, on the ecology and biological activity of the main EO components. In all three species, two basic trichome morphotypes (flagellar non-glandular and biseriate glandular) occurred with different distribution patterns. The glandular ones produced terpenes, along with flavonoids. A high level of chemical variability in the EO compositions emerged, specifically for qualitative data. T. vulgare profile was more complex and heterogeneous than those obtained from T. parthenium and T. corymbosum , with camphor as the predominant compound, followed by farnesol and α-santalone, respectively. Finally, the obtained scientific findings were made available to the visitors of the botanic garden through new dissemination labeling that highlights the "invisible", microscopic features of the plants, from an Open Science perspective ("Botanic Garden, factories of molecules…work in progress"-Lombardy Region Project Lr. 25/2016, year 2021).

The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: Head and Neck Cancer (HNC) has a high incidence and prevalence in the worldwide population. The broad terminology associated with these diseases and their multimodality treatments generates large amounts of heterogeneous clinical data, which motivates the construction of a high-quality harmonization model to standardize this multi-source clinical data in terms of format and semantics. The use of ontologies and semantic techniques is a well-known approach to face this challenge., Objective: This work aims to provide a clinically reliable data model for HNC processes during all phases of the disease: prognosis, treatment, and follow-up. Therefore, we built the first ontology specifically focused on the HNC domain, named HeNeCOn (Head and Neck Cancer Ontology)., Methods: First, an annotated dataset was established to provide a formal reference description of HNC. Then, 170 clinical variables were organized into a taxonomy, and later expanded and mapped to formalize and integrate multiple databases into the HeNeCOn ontology. The outcomes of this iterative process were reviewed and validated by clinicians and statisticians., Results: HeNeCOn is an ontology consisting of 502 classes, a taxonomy with a hierarchical structure, semantic definitions of 283 medical terms and detailed relations between them, which can be used as a tool for information extraction and knowledge management., Conclusion: HeNeCOn is a reusable, extendible and standardized ontology which establishes a reference data model for terminology structure and standard definitions in the Head and Neck Cancer domain. This ontology allows handling both current and newly generated knowledge in Head and Neck cancer research, by means of data linking and mapping with other public ontologies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)