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Background and Objectives: Psychosocial stress is a potentially modifiable risk factor of early-onset ischemic stroke, with limited evidence suggesting a stronger association between stress and cryptogenic ischemic stroke (CIS) compared with strokes of known etiology. We aimed to explore the association between self-perceived stress and CIS, with subgroup analyses stratified by sex and age., Methods: Young patients aged 18-49 years with a first-ever CIS and sex-matched and age-matched stroke-free controls from 19 European centers were included. Self-perceived stress was assessed using a modified version of the Perceived Stress Scale (PSS). Scores were categorized into low (0-13), moderate (14-26), and high (27-40) perceived stress. Conditional logistic regression-adjusted for age, level of education, traditional risk factors (hypertension, cardiovascular diseases, diabetes mellitus, heavy alcohol consumption, current smoking, obesity, diet, depression, and physical inactivity), and migraine with aura (MA)-was used to assess independent association between self-perceived stress and CIS., Results: Altogether, 426 patients (median age 41 years; 47.7% women) and 426 controls were included. Patients were more often at least moderately stressed compared with controls (46.2% vs 33.3%, p < 0.001). In the entire study population, higher self-perceived stress as a discrete measure was independently associated with CIS: adjusted odds ratio (OR) 1.04 per point increase; 95% CI 1.01-1.07. Categorical PSS score analysis showed an independent association between moderate stress and CIS (OR 1.47; 95% CI 1.00-2.14), but not with high stress (2.62; 0.81-8.45). In sex-specific analysis, higher stress as a discrete measure was associated with CIS in women (1.06; 1.02-1.11), but not in men (1.02; 0.97-1.07). Moderate stress was associated with CIS in women (1.78; 1.07-2.96), but not in men (1.06; 0.58-1.96). When stratified by age, higher stress as a discrete measure was significantly associated with CIS only in patients aged 18-39 years (1.06; 1.00-1.11)., Discussion: Self-perceived stress was strongly correlated with an increased risk of early-onset CIS, even after robust adjustment for cardiovascular risk factors and MA. These findings highlight the need for further investigation into the mechanisms by which stress may contribute to the risk of CIS. Possibility of recall bias should be considered when interpreting the results., Trial Registration Information: Clinical trial registration number: NCT01934725.

Context: Amyotrophic Lateral Sclerosis (ALS) is a progressive and fatal neurodegenerative disorder which poses multidimensional burden to patients and caregivers., Objectives: This study aimed to investigate spiritual needs in people with Amyotrophic Lateral Sclerosis (pALS) and their closest caregivers, and to identify factors which may contribute to these needs., Methods: Spiritual needs were assessed based on the Spiritual Needs Questionnaire (SpNQ) as part of a longitudinal cohort study in pALS and their closest caregivers who were included in a multiprofessional pilot project for ALS in Southern Germany with a focus on neuropalliative care., Results: About 61 pALS and 52 caregivers were assessed for their spiritual needs. We show that both pALS and their caregivers maintain stable and distinct spiritual needs over time, irrespective of age, gender, care setting, or perceived level of loneliness. While pALS emphasize generativity and inner peace needs, caregivers primarily focus on finding inner peace, which they value even more than pALS., Conclusions: Both pALS and their caregivers have strong unmet spiritual, and particularly nonreligious needs, which should be regularly assessed by the interprofessional team. Documenting these needs is the initial step in the spiritual care process, which requires a collaborative response from the interprofessional team. All healthcare professionals involved in ALS care should be attuned to the potential for unmet spiritual needs in patients and their caregivers. Early identification of these needs can facilitate the initiation of appropriate support processes., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

The exogenous siRNA (exo-siRNA) pathway is a critical RNA interference response involved in controlling arbovirus replication in mosquito cells. It is initiated by the detection of viral long double-stranded RNA (dsRNA) by the RNase III enzyme Dicer 2 (Dcr2), which is processed into predominantly 21 nucleotide (nt) virus-derived small interfering RNAs, or vsiRNAs that are taken up by the Argonaute 2 (Ago2) protein to target viral single-stranded RNAs. The detailed understanding of Dicer structure, function and domains owes much to studies outside the context of viral infection and studies in model organisms, and as such how Dcr2 domains contribute to detecting viral dsRNA to mount antiviral responses in infected mosquito cells remains less well understood. Here, we used a Dcr2 reconstitution system in Aedes aegypti derived Dcr2 KO cells to assess the contribution of the PAZ domain to induction of the exo-siRNA pathway following infection with Semliki Forest virus (SFV; Togaviridae, Alphavirus). Amino acids critical for PAZ activity were identified, and loss of PAZ function affected the production of 21 nt vsiRNAs -with enrichment of 22 nt SFV-derived small RNAs observed- and silencing activity. This study establishes PAZ domain's functional contribution to Dcr2 processing of viral dsRNA to 21 nt vsiRNAs., (Published by Cold Spring Harbor Laboratory Press for the RNA Society.)

Objective: Lower platelet monoamine oxidase (MAO) activity has consistently been associated with excessive risk-taking and general psychiatric vulnerability. How this peripheral measure can represent presumably centrally regulated complex behaviours is not clear but platelet MAO activity has been suggested to reflect the capacity of serotonin release in the brain. Secretion of prolactin is in part under serotonergic control and indicates serotonin release capacity., Methods: We have assessed release of prolactin and other exercise-induced hormones in response to strenuous physical exercise in twenty male subjects and examined its association with platelet MAO activity as measured radioenzymatically., Results: Increase in prolactin levels was positively correlated with platelet MAO activity. Levels of cortisol, growth hormone and aldosterone were also raised by exercise, but these increases were not associated with platelet MAO activity. Unexpectedly, aldosterone levels before exercise were also in a positive correlation with platelet MAO activity., Conclusion: The finding that exercise-induced prolactin release is associated with MAO activity in platelets indirectly supports the notion that platelet MAO activity is a marker of central serotonin release capacity., 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 © 2025 Elsevier B.V. All rights reserved.)

There is substantial evidence for an association between the Five-Factor Model personality domains and cognition across adulthood. Examining the items that compose each of the five domains, known as nuances, can provide novel insight into the aspects of the traits most connected to cognitive outcomes. This study tested the association between personality nuances and cognition (memory performance, subjective memory, informant-rated cognition) in five community-based cohorts. Participants (N > 28,000, age range: 32-104 years) were administered the Midlife Development Inventory (MIDI) to assess personality nuances, immediate and recall tasks to assess memory performance, and a subjective memory measure. Ratings of cognitive functioning from a knowledgeable informant were available in two samples. There was a strong pattern of replicability between personality items and cognitive outcomes across samples and cognitive measures. Meta-analyses indicated that higher neuroticism nuances (particularly the nervous and worry items) were related to lower memory performance, worse subjective memory, and worse informant-rated cognition. Higher conscientiousness (particularly the organized and responsible items), extraversion (particularly the active item), and openness (particularly the intelligent item) nuances were consistently associated with better memory performance, better subjective memory, and better informant-rated cognition across samples. To a lesser extent, higher agreeableness nuances (helpful, warm, sympathetic) were associated with better memory and subjective memory. This research adds to the existing literature by providing novel evidence of replicable associations between personality nuances and cognition., Competing Interests: Declaration of competing interest None., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Understanding the intricate interplay between plant and soil microbiomes and their effects on plant growth and productivity is vital in a rapidly changing climate. This review explores the interconnected impacts of climate change on plant-soil microbiomes and their profound effects on agricultural productivity. The ongoing rise in global temperatures, shifting precipitation patterns and extreme weather events significantly affect the composition and function of microbial communities in the rhizosphere. Changes in microbial diversity and activity due to rising temperatures impact nutrient cycling, microbial enzyme synthesis, soil health and pest and disease management. These changes also influence the dynamics of soil microbe communities and their capability to promote plant health. As the climate changes, plants' adaptive capacity and microbial partners become increasingly crucial for sustaining agriculture. Mitigating the adverse effects of climate change on plant growth and agricultural productivity requires a comprehensive understanding of the interconnected mechanisms driving these processes. It highlights various strategies for mitigating and adapting to environmental challenges, including soil management, stress-tolerant crops, cover cropping, sustainable land and water management, crop rotation, organic amendments and the development of climate-resilient crop varieties. It emphasises the need for further exploration of plant-soil microbiomes within the broader context of climate change. Promising mitigation strategies, including precision agriculture and targeted microbiome modifications, offer valuable pathways for future research and practical implementation of global food security and climate change., (© 2025 John Wiley & Sons Ltd.)

Rewards are rewarding owing to their hedonic or metabolic value. Individual differences in sensitivity to rewards are predictive of mental health problems but may reflect variation in metabolic types. We have assessed the association of two distinguishable aspects of reward sensitivity, openness to rewards (the striving towards multiple rewards) and insatiability by reward (the strong pursuit and fixation to a particular reward), with measures of metabolism and activity in a longitudinal study of representative birth cohort samples. We used data of the Estonian Children Personality Behaviour and Health Study (original n = 1238) collected at age 15, 18 and 25. Reward sensitivity and physical activity were self-reported during a laboratory visit, when also blood sampling, measurement of blood pressure, height and weight, aerobic exercise testing and the diet interview, after the participants had kept food diary, took place. In the younger cohort, physical activity was also assessed by accelerometry at age 18 and 25. Across adolescence and young adulthood, openness to rewards was positively associated with physical activity and negatively with blood pressure and serum levels of glucose, insulin and cholesterol levels. In contrast, insatiability by reward was positively associated with serum triglyceride levels and negatively with energy intake and cardiorespiratory fitness. In conclusion, the two facets of reward sensitivity have a fairly different association with a variety of metabolic and health-related measures. This may explain the variable findings in literature, and suggests that individual differences in reward sensitivity are part of a complex physiological variability, including energy expenditure profiles.

Tropical peatlands are significant sources of methane (CH₄), but their contribution to the global CH₄ budget remains poorly quantified due to the lack of long-term, continuous and high-frequency flux measurements. To address this gap, we measured net ecosystem CH 4 exchange (NEE-CH 4 ) using eddy covariance technique throughout the conversion of a tropical peat swamp forest to an oil palm plantation. This encompassed the periods before, during and after conversion periods from 2014 to 2020, during which substantial environmental shifts were observed. Draining the peatland substantially lowered mean monthly groundwater levels from -20.0 ± 14.2 cm before conversion to -102.3 ± 31.6 cm during conversion and increased slightly to -96.5 ± 19.3 cm after conversion. Forest removal increased mean monthly soil temperature by 2.3 to 3.1 °C, reducing net radiation (R n ) and raising vapor pressure deficit (VPD). Following the tree removal, controlled burning temporarily warmed air temperature by 8 °C, increased VPD and significantly attenuated R n , resulting in negative values owing to radiation interception by smoke and increased surface warming. Contrary to expectations that drainage would lower CH 4 emissions, the site remained a consistent net source, with even higher emissions observed during and after conversion. The mean monthly NEE-CH 4 during conversion (23.3 ± 8.6 mg C m -2 d -1 ) was about 2-times higher than before conversion (12.1 ± 5.3 mg C m -2 d -1 ) and about 1.5-times higher than after conversion (16.3 ± 4.1 mg C m -2 d -1 ). The heightened CH 4 release is likely attributable to emissions from drainage ditches, underscoring their significant role in post-conversion CH 4 dynamics. Despite its short duration, controlled burning substantially elevated NEE-CH 4 , ranging from 0.04 to 0.91 mg C m -2  s -1 . Our findings highlight the substantial impact of land conversion on peatland CH 4 dynamics, emphasizing the need for accurate flux measurements across various conversion stages to refine global CH 4 budgets., 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 © 2025 Elsevier B.V. All rights reserved.)

Purpose: The primary aim of this study was to investigate how speech-language pathologists (SLPs) from Estonia, Finland, and Lithuania rate the significance of different features for diagnosing childhood apraxia of speech (CAS) in their languages., Method: An online survey was conducted among 197 Estonian, Finnish, and Lithuanian SLPs who have worked with children with CAS. The SLPs were asked to rate the significance of 63 features for CAS diagnosis in their respective language. Cross-linguistic patterns in diagnostic features were examined with simple correspondence analysis (SCA) and via descriptive statistics., Results: The ratings revealed six to seven diagnostic features that were considered very significant for CAS diagnosis by the majority of respondents in each country. The SCA highlighted differences between Lithuanian SLPs and Estonian and Finnish SLPs. Some possible language-specific associations were noted, such as palatalization errors for Lithuanian and Estonian and diphthong distortions for Estonian. The respondents from all countries rated highly those features that can easily be applied to most languages (e.g., groping) and gave lower ratings to features that may be influenced by the linguistic structure of different languages (e.g., word stress errors)., Conclusions: Overall, SLPs provided high ratings to CAS features that occur universally across languages, whereas features specific to languages, such as prosody-related errors, were not as highly rated. Several language-specific features were highlighted, providing direction for future research and emphasizing the importance of language-specific considerations in CAS research and diagnosis.

We present a novel framework for understanding the diverse spectrum of mental breakthrough events, ranging from problem-solving insights to profound personal transformations. We propose that these events, while varied in expression and impact, share common underlying mechanisms of representational change. We also hypothesise that the differences in phenomenological intensity can be conceptualized along a continuum. Central to our model are three core components - tension, altered salience, and enhanced flexibility - which we identify as essential prerequisites for significant cognitive restructuring. These components interact within an iterative cycle, influencing both the emergence and nature of insight experiences. Drawing on examples from different fields, we explore how a conflict between existing models can trigger this cycle, wherein mechanisms of attention allocation and relaxation of constraints work in tandem to facilitate the emergence of insights. Furthermore, we propose that the intensity of the "aha-moment" and the breadth of its impact are contingent on how central the conflict is within one's conceptual landscape and the extent to which existing mental models are challenged. Thus, the model accounts for both the subtle, momentary insights in problem-solving and the transformative realizations that reshape core beliefs and self-perception. By synthesising insights from various domains, including psychotherapy, contemplative science, and psychedelic research, we present a theoretical account with broad scope, aiming to shed light on the complex processes that can lead to a wide array of mental breakthroughs, thereby contributing to the understanding of insight phenomena across disciplines., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Pharmacogenomics is central to precision medicine, informing medication safety and efficacy. Pharmacogenomic diplotyping of complex genes requires full-length DNA sequences and detection of structural rearrangements. We introduce StarPhase, a tool that leverages PacBio HiFi sequence data to diplotype 21 CPIC Level A pharmacogenes and provides detailed haplotypes and supporting visualizations for HLA-A , HLA-B , and CYP2D6 . StarPhase diplotypes have high concordance with benchmarks where 99.5% are either exact matches or minor discrepancies. Manual inspection of the 0.5% mismatches indicates they were correctly called by StarPhase. With StarPhase, we update or correct 26.2% of GeT-RM pharmacogenomic diplotypes. Population distributions from StarPhase mostly reflect those of the All of Us cohort, while also highlighting gaps in existing pharmacogenomic databases that long-read sequencing can fill. With a single HiFi whole genome sequencing assay, StarPhase enables robust PGx diplotyping even as additional pharmacogenes and haplotypes are discovered.

Aims: Both erectile dysfunction (ED) and diabetes (DM) are common health problems that share risk factors. The aim of this study was to investigate whether ED can predict glucose metabolism dysfunctions in men at the primary care level., Methods: An 11-year population-based cohort study was conducted in men born between 1933 and 1956. The baseline survey was conducted in 2007-2008, with a follow-up examination 11 years later. The International Index of Erectile Function (IIEF-5) questionnaire was used to assess erectile function. Dysglycemia was evaluated using and a 2-hour oral glucose tolerance test (2hOGTT), in combination with health registry data., Results: At baseline, men with ED but without a history of known DM exhibited a significantly higher prevalence of undetected DM, odds ratio (OR) 4.7 (95 % CI 1.6, 14.4), and preDM, OR 1.9 (1.1, 3.2), compared with men without ED. Over an 11-year follow-up period, a significantly increased cumulative incidence of DM was observed in men who reported symptoms of ED at the start of the study., Conclusions: The symptoms of ED appear to be an early warning sign of existing DM and preDM and predict an increased risk of developing abnormal glucose metabolism in the future., (Copyright © 2024 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Background: Acute mesenteric venous thrombosis (MVT) is rarely suspected as primary diagnosis in emergency departments and still carries an in-hospital mortality rate of above 20%., Objectives: The aim of this study was to find differences in clinical and laboratory markers between patients with acute MVT and a control group of suspected but confirmed as not having any type of acute mesenteric ischaemia (AMI)., Design: Data was retrieved from the AMESI (Acute MESenteric Ischaemia) study. This international, multicenter prospective case-control study from 32 sites collected data on patients with suspected AMI during a 10-month period., Methods: Independent factors associated with acute MVT were evaluated in a multivariable logistic regression analysis and expressed as odds ratios (OR) with 95% confidence intervals (CI)., Results: D-dimer was not significantly higher in MVT (n = 73) compared to non-AMI (n = 287) patients (median 7.0 mg/L vs 4.5 mg/L, P  = .092). After entering BMI, atherosclerotic disease, history of venous thromboembolism, CRP, and D-dimer as covariates in a multi-variable logistic regression analysis, absence of atherosclerotic disease (OR 0.096, 95% CI 0.011-0.84; P  = .034) and elevated D-dimer (OR 2.59/one SD increment, 95% CI 1.07-6.28; P  = .034) were associated with MVT. The discriminative ability of D-dimer for MVT as assessed by area under the curve in the receiver operating characteristics analysis was 0.63 (95% CI 0.49-0.78)., Conclusion: Elevated D-dimer was associated with MVT, but the discriminative ability of D-dimer was poor. There is an urgent need to find a more accurate plasma biomarker for this condition., Trial Registration: NCT05218863 (registered 19.01.2022)., (© The Author(s) 2024.)

Background: Our aim was to assess the relationships of cardiovascular health metrics, cardiorespiratory fitness, lean mass, and fat percentage with arterial structure and function from childhood to adolescence., Methods and Results: Five hundred four children aged 6 to 9 years were examined in the PANIC (Physical Activity and Nutrition in Children) study at baseline, 2 and 8 years later. The associations of adjusted American Heart Association cardiovascular health metrics (smoking status, body mass index-SD score, moderate-to-vigorous physical activity, diet quality, plasma total cholesterol, systolic blood pressure, plasma glucose categorized into poor, intermediate, and ideal), the American Heart Association cardiovascular health score, cardiorespiratory fitness measured by maximal oxygen uptake in a bicycle exercise test, lean mass and fat percentage with carotid intima-media thickness (cIMT) and pulse wave velocity (PWV) were analyzed cross-sectionally and longitudinally in 277 participants at age 15 to 17 years. Higher American Heart Association cardiovascular health score at baseline was associated with lower PWV at 8-year follow-up (ß, -0.19 [95% CI, -0.32 to -0.05]). Higher body mass index-SD score and systolic blood pressure were associated with higher cIMT (ß, 0.18 [95% CI, 0.05-0.31]); and (ß, 0.13 [95% CI, 0.00-0.25]; respectively) and PWV (ß, 0.20 [95% CI, 0.07-0.34]) and (ß, 0.13 [95% CI, 0.00-0.26]; respectively) at 8-year follow-up. Higher moderate-to-vigorous physical activity was associated with higher cIMT (ß, 0.25 [95% CI, 0.07-0.43]); yet lower PWV (ß, -0.25 [95% CI, -0.44 to -0.06]) at 8-year follow-up. Better cardiorespiratory fitness (ß, 0.29 [95% CI, 0.08-0.51]) and higher lean mass (ß, 0.51 [95% CI, 0.03-0.98]) were associated with higher cIMT after accounting for American Heart Association cardiovascular health score at 8-year follow-up., Conclusions: While our results suggest that higher cardiometabolic risk factors in childhood may exert unfavorable effects on arterial health during adolescence, we demonstrated the complexity of relationships between cardiovascular health metrics and arterial health indicators in childhood and adolescence. We found different associations of cardiovascular health metrics with cIMT and PWV in childhood and adolescence, calling for caution when interpreting the results of various cardiovascular risk factors with measures of arterial health, particularly in youth., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01803776.

Drainage intensity and forest management in peatlands affect carbon dioxide (CO 2 ) emissions to the atmosphere and export of dissolved organic carbon (DOC) to water courses. The peatland carbon (C) balance results from a complex network of ecosystem processes from where lateral C fluxes have typically been ignored. Here, we present a new version of the SUSI Peatland simulator, the first advanced process-based ecosystem model that compiles a full C balance in drained forested peatland including DOC formation, transport and biodegradation. SUSI considers site, stand and terrain characteristics as well as the interactions and feedbacks between ecosystem processes and offers novel ways to evaluate and mitigate adverse environmental impacts with thorough management planning. Here, we extended SUSI by designing and parameterizing a mass-balance based decomposition module (ESOM) based on literature findings and tested the ESOM performance against an independent dataset measured in the laboratory using peat columns collected from Finland, Estonia, Sweden and Ireland. ESOM predicted the CO 2 emissions and changes in DOC concentrations with a reasonable accuracy for the peat columns. We applied the new SUSI for drained peatland sites and found that reducing the depth to which ditches are cleaned by 0.3 m decreased the annual DOC export by 34 (17 %), 29 (19 %) and 7 (5 %) kg ha -1 in Finland, Estonia and Sweden, respectively, using typical ditch spacing for these countries. Correspondingly, site annual C sink increased by 305, 409 and 32 kg ha -1 in Finland, Estonia and Sweden, respectively. Our results also indicated that terrain slope can markedly alter the water residence time and consequently DOC biodegradation and export to ditches. We conclude that DOC export can be decreased and site C sink increased by reducing the depth to which ditches are cleaned or by increasing the ditch spacing., 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.)

In the present work, we addressed the relationship between parental leave policies and social norms. Using a pre-registered, cross-national approach, we examined the relationship between parental leave policies and the perception of social norms for the gender division of childcare. In this study, 19,259 students (11,924 women) from 48 countries indicated the degree to which they believe childcare is (descriptive norm) and should be (prescriptive norm) equally divided among mothers and fathers. Policies were primarily operationalized as the existence of parental leave options in the respective country. The descriptive and prescriptive norms of equal division of childcare were stronger when parental leave was available in a country - also when controlling for potential confounding variables. Moreover, analyses of time since policy change suggested that policy change may initially affect prescriptive norms and then descriptive norms at a later point. However, due to the cross-sectional nature of the data, drawing causal inferences is difficult., (© 2024 British Psychological Society.)

Phylogenomic approaches have recently helped elucidate various insect relationships, but large-scale comprehensive analyses on relationships within sawflies and woodwasps are still lacking. Here, we infer the relationships and long-term biogeographic history of these hymenopteran groups using a large dataset of 354 UCE loci collected from 385 species that represent all major lineages. Early Hymenoptera started diversifying during the Early Triassic ∼249 Ma and spread all over the ancient supercontinent Pangaea. We recovered Xyeloidea as a monophyletic sister group to other Hymenoptera and Pamphilioidea as sister to Unicalcarida. Within the diverse family Tenthredinidae, our taxonomically and geographically expanded taxon sampling highlights the non-monophyly of several traditionally defined subfamilies. In addition, the recent removal of Athalia and related genera from the Tenthredinidae into the separate family Athaliidae is supported. The deep historical biogeography of the group is characterised by independent dispersals and re-colonisations between the northern (Laurasia) and southern (Gondwana) palaeocontinents. The breakup of these landmasses led to ancient vicariance in several Gondwanan lineages, while interchange across the Northern Hemisphere has continued until the Recent. The little-studied African sawfly fauna is likewise a diverse mixture of groups with varying routes of colonization. Our results reveal interesting parallels in the evolution and biogeography of early hymenopterans and other ancient insect groups., 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 Author(s). Published by Elsevier Inc. All rights reserved.)

Background: While gastrointestinal (GI) dysfunction is commonly encountered among critically ill patients, a uniform prospectively validated scoring system is lacking. The present study aims to validate the recently developed Gastrointestinal Dysfunction Score (GIDS) in a multicenter, prospective cohort of consecutive adult patients admitted to intensive care units (ICU)., Methods: GUTPHOS is a prospective, multicenter, non-interventional cohort study in which at least 1400 consecutive adult patients (age ≥18 years) admitted to the ICU will be monitored daily for abdominal signs and symptoms of GI dysfunction. The previously developed GIDS constructed from these signs and symptoms will be tested in relation to mortality and duration of ICU dependency and parenteral nutrition (PN) dependency. Between January and June 2024, each participating clinical site will include 50-120 consecutive patients over an eight-week period. Study data will be collected in three phases: baseline data upon ICU admission, daily observations throughout a maximum of 7 days in ICU or until discharge, and a follow-up period of 90 days. The primary outcomes are 28- and 90-day all-cause mortality. Secondary outcomes include ICU and hospital mortality, ICU and hospital length of stay, days alive and free of ICU by day 28 and day 90, days alive and free of hospital by day 28 and day 90, and days alive and free of organ support and PN dependency by day 28., Discussion: The GUTPHOS study will be the first worldwide, multicenter, prospective, observational cohort study to validate the GIDS in adult patients admitted to ICUs against 28- and 90-day mortality. The availability of a validated tool will allow its use in interventional studies that are currently hindered by the lack of a validated measurement tool for GI dysfunction., Clinical Trial Registry: NCT05909722., Competing Interests: Declaration of competing interest IWKK received a Veni Fellowship (2024–2028) through the Dutch Research Council (NWO Talent Program). SJS received grants and non-financial support from Reactive Robotics GmbH (Munich, Germany), ASP GmbH (Attendorn, Germany), STIMIT AG (Biel, Switzerland), ESICM (Geneva, Switzerland), grants, personal fees, and non-financial support from Fresenius Kabi Deutschland GmbH (Bad Homburg, Germany), grants from the Innovationsfond of The Federal Joint Committee (G-BA), personal fees from Springer Verlag GmbH (Vienna, Austria) for educational purposes and Advanz Pharma GmbH (Bielefeld, Germany), non-financial support from national and international societies (and their congress organizers) in the field of anesthesiology and intensive care medicine, outside the submitted work. SJS holds stocks in small amounts from Alphabet Inc., Bayer AG, and Siemens AG; these holdings have not affected any decisions regarding his research or this study. ARHvZ reported receiving honoraria for advisory board meetings, lectures, research, and travel expenses from Abbott, AOP Pharma, Baxter, Cardinal Health, Danone-Nutricia, Fresenius Kabi, GE Healthcare, Medcaptain, Nestlé, PAION, and Rousselot. ARB received speaker or consulting fees from Nutricia and VIPUN Medical. JG is granted a senior clinical investigator fellowship by Research Foundation – Flanders (1842724N) and has obtained research funding through grants from KU Leuven (STG/23/032) and the European Society of Intensive Care Medicine (Fundamental Research Award 2022). MPC has obtained research funding by grants from Research Foundation Flanders, KU Leuven and Department for Innovation of the Flanders Government, and reported receiving consulting fees from Baxter and VIPUN. MLNGM reported receiving honoraria for advisory board meetings, lectures, research, and travel expenses from Getinge, Serenno Medical, Potrero Medical, Sentinel Medical, Baxter, BBraun, Becton Dickinson, ConvaTec, Spiegelberg, Medtronic, MedCaptain, and Holtech Medical, and PeerVoice. He holds stock options for Sentinel, Serenno and Potrero. The other authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Aberrations in blood phosphate (Pi) levels, whether presenting as hypo- or hyperphosphatemia, appear to be associated with clinical complications and adverse outcomes in patients admitted to an intensive care unit (ICU). However, the prevalence of Pi disorders and the association with subsequent factors and organ failures leading to death in ICU patients are poorly described. Despite endeavors to understand the etiology and treatment of low Pi levels from systematic reviews and meta-analyses, the literature lacks comprehensive guidance for managing hypophosphatemia. Hyperphosphatemia, on the other hand, appears to be associated with higher mortality among critically ill patients, yet its prevalence among ICU patients, particularly following phosphate repletion, remains unknown. The present study aims to investigate the prevalence of Pi abnormalities upon ICU admission and their incidence during the first week of ICU stay, the factors associated with Pi alterations, and the effect of phosphate repletion on the normalization of Pi levels, and its associations with clinical outcomes., Methods: This multicentre, prospective, non-interventional cohort study will include at least 1000 consecutive adult ICU patients (≥18 years) as part B of the GUTPHOS study. Sites are eligible if an anticipated minimal inclusion of 50 eligible patients during eight weeks from January 2024 until June 2024 and daily phosphate measurements during the first seven days of ICU stay are expected. All consecutive adult patients admitted to a participating ICU during the recruitment period, lasting up to eight weeks, or up to 120 patients if enrollment reaches that limit earlier, will be included. Study parameters include study site characteristics, patient demographics, daily assessment of Pi levels, Pi-related treatment, feeding details, renal replacement therapy details, the incidence of refeeding-associated hypophosphatemia and administered medication (during the first seven calendar days of ICU stay). There will be a follow-up period of a maximum of 90 days to document 28- and 90-day all-cause mortality as the primary outcome. Multiple logistic regression will be used to assess independent associations with mortality in addition to Receiver Operating Characteristics curves to identify cut-off Pi values associated with mortality and overcorrection. Linear mixed models will be conducted to assess Pi treatment effects. Subgroup analyses will be performed based on Pi abnormalities observed during ICU admission, categorized as normo-, hypo-, hyper-, or mixed, along with its severity (mild, moderate, or severe)., Discussion: The GUTPHOS study will be the first multicentre, prospective observational cohort study to investigate the prevalence, management practices, and consequent outcomes associated with Pi abnormalities during the first week of ICU admission. Its results may bridge the current evidence gap in repletion protocols while establishing the groundwork for a subsequent randomized controlled trial., Clinical Trial Registry: NCT05909722., Competing Interests: Declaration of competing interest IWKK received a Veni Fellowship (2024–2028) through the Dutch Research Council (NWO Talent Program). SJS received grants and non-financial support from Reactive Robotics GmbH (Munich, Germany), ASP GmbH (Attendorn, Germany), STIMIT AG (Biel, Switzerland), ESICM (Geneva, Switzerland), grants, personal fees, and non-financial support from Fresenius Kabi Deutschland GmbH (Bad Homburg, Germany), grants from the Innovationsfond of The Federal Joint Committee (G-BA), personal fees from Springer Verlag GmbH (Vienna, Austria) for educational purposes and Advanz Pharma GmbH (Bielefeld, Germany), non-financial support from national and international societies (and their congress organizers) in the field of anesthesiology and intensive care medicine, outside the submitted work. SJS holds stocks in small amounts from Alphabet Inc., Bayer AG, and Siemens AG; these holdings have not affected any decisions regarding his research or this study. ARHvZ reported receiving honoraria for advisory board meetings, lectures, research, and travel expenses from Abbott, AOP Pharma, Baxter, Cardinal Health, Danone-Nutricia, Fresenius Kabi, GE Healthcare, Medcaptain, Nestlé, PAION, and Rousselot. ARB received speaker or consulting fees from Nutricia and VIPUN Medical and is holding a grant from Estonian Research Council (PRG1255). MPC has obtained research funding by grants from Research Foundation Flanders, KU Leuven and Department for Innovation of the Flanders Government, and reported receiving consulting fees from Baxter and VIPUN. MLNGM reported receiving honoraria for advisory board meetings, lectures, research, and travel expenses from Getinge, Serenno Medical, Potrero Medical, Sentinel Medical, Baxter, BBraun, Becton Dickinson, ConvaTec, Spiegelberg, Medtronic, MedCaptain, and Holtech Medical, and PeerVoice. He holds stock options for Sentinel, Serenno and Potrero. JG is granted a senior clinical investigator fellowship by Research Foundation – Flanders (1842724N), and has obtained research funding by grants from KU Leuven (STG/23/032) and the European Society of Intensive Care Medicine (Fundamental Research Award 2022). The other authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: E-i-C of Consciousness and Cognition (an Elsevier journal). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Variable expressivity of disease-associated variants implies a role for secondary variants that modify clinical features. We assessed the effects of modifier variants towards clinical outcomes of 2,252 individuals with primary variants. Among 132 families with the 16p12.1 deletion, distinct rare and common variant classes conferred risk for specific developmental features, including short tandem repeats for neurological defects and SNVs for microcephaly, while additional disease-associated variants conferred multiple genetic diagnoses. Within disease and population cohorts of 773 individuals with the 16p12.1 deletion, we found opposing effects of secondary variants towards clinical features across ascertainments. Additional analysis of 1,479 probands with other primary variants, such as 16p11.2 deletion and CHD8 variants, and 1,084 without primary variants, showed that phenotypic associations differed by primary variant context and were influenced by synergistic interactions between primary and secondary variants. Our study provides a paradigm to dissect the genomic architecture of complex disorders towards personalized treatment., Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests.

Objective: Our study investigates the impact of copy number variations (CNVs) on Parkinson's disease (PD) pathogenesis using genome-wide data, aiming to uncover novel genetic mechanisms and improve the understanding of the role of CNVs in sporadic PD., Methods: We applied a sliding window approach to perform CNV-GWAS and conducted genome-wide burden analyses on CNV data from 11,035 PD patients (including 2,731 early-onset PD (EOPD)) and 8,901 controls from the COURAGE-PD consortium., Results: We identified 14 genome-wide significant CNV loci associated with PD, including one deletion and 13 duplications. Among these, duplications in 7q22.1, 11q12.3 and 7q33 displayed the highest effect. Two significant duplications overlapped with PD-related genes SNCA and VPS13C , but none overlapped with recent significant SNP-based GWAS findings. Five duplications included genes associated with neurological disease, and four overlapping genes were dosage-sensitive and intolerant to loss-of-function variants. Enriched pathways included neurodegeneration, steroid hormone biosynthesis, and lipid metabolism. In early-onset cases, four loci were significantly associated with EOPD, including three known duplications and one novel deletion in PRKN . CNV burden analysis showed a higher prevalence of CNVs in PD-related genes in patients compared to controls (OR=1.56 [1.18-2.09], p=0.0013), with PRKN showing the highest burden (OR=1.47 [1.10-1.98], p=0.026). Patients with CNVs in PRKN had an earlier disease onset. Burden analysis with controls and EOPD patients showed similar results., Interpretation: This is the largest CNV-based GWAS in PD identifying novel CNV regions and confirming the significant CNV burden in EOPD, primarily driven by the PRKN gene, warranting further investigation.

Problematic use of social networking sites (SNS) has a negative impact on mental health. It has been found that people who score high on neuroticism are especially vulnerable towards engaging with SNS in a problematic way but it is not clear which psychological mechanisms explain this relationship. We addressed this issue by examining the mediating role of fear of missing out and self-control in the relationship between neuroticism and problematic SNS use. For this purpose, we conducted a cross-sectional study ( n = 151, 69.5% female, M age = 26.23, SD = 7.52) and tested for parallel mediation using structural equation modelling. Neuroticism was found to be predictive of increased levels of problematic SNS use. Moreover, neuroticism was associated with both increased levels of fear of missing out and decreased levels of self-control. However, only fear of missing out was found to robustly mediate the relationship between neuroticism and problematic use of SNS. These findings suggest that fear of missing out could be an intervention target to prevent people scoring high on neuroticism from engaging in problematic SNS use., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Collaborative and innovative educational approaches are essential to building nurses' competencies in responding to healthcare challenges and to enhance high-quality nursing practice. Nurses are increasingly learning in various contexts, and thus, the understanding and organising of collaborative learning needs further exploration., Aim: To describe collaborative learning in nursing practice and education from the point of view of nurses, involved as students and teachers in master's education in nursing., Design and Methods: Qualitative study using semi-structured focus groups involving 33 nurses as master's students and teachers from Estonia and Norway. The data were analysed using inductive content analysis., Findings: The essence of collaborative learning in the context of nursing practice and education was identified as the aggregation of diverse learners' skills and reflections while working towards shared aims. This fostered the development of workplace competencies, professional attitudes, and personal growth. Organising collaborative learning requires careful planning and synchronisation between clinical and educational organisations., Conclusions: Collaborative learning is an inclusive method, aiding nurses at different phases of their career to gain knowledge and enhance their soft skills, and potentially reducing professional hierarchies. Further research is needed to develop methods for evaluating the outcomes of collaborative learning., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Nurses should have appropriate education and required competencies to provide high-quality palliative care. The aim of this international multisite study was to list and evaluate core palliative care competencies that European nurses need to achieve in their education to provide palliative care. Methods: The Nominal Group Technique (NGT) was used as a data collection method. NGT meetings were organized in four European countries. Targeted groups of palliative care professionals with diverse contextual and professional backgrounds participated in the NGTs. The research question was: "What are the core competencies in palliative care that need to be achieved during undergraduate nursing education?" Data analysis was done in two stages: grouping the top 10 answers based on similarities and thematic synthesis based on all the ideas produced during the NGTs. Results: Palliative care core competencies based on the research were (1) competence in the characteristics of palliative care; (2) competence in decision-making and enabling palliative care; (3) symptom management competence in palliative care; (4) competence in holistic support in palliative care; (5) active person- and family-centered communication competence in palliative care; (6) competence in empathy in palliative care; (7) spiritual competence in palliative care; (8) competence in ethical and legal issues in palliative care; (9) teamwork competence in palliative care; and (10) self-awareness and self-reflection competence in palliative care. Conclusions: It was possible to find differences and similarities in the top 10 palliative care core competencies from different countries. Thematic synthesis of all the data showed that there were various competencies needed for nursing students to provide quality palliative care., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Personality traits are broad constructs composed of nuances, operationalized by personality items, that can provide a more granular understanding of personality associations with health outcomes. This study examined the associations between personality nuances and incident dementia and evaluated whether nuances associations replicate across two samples. Health and Retirement Study (HRS, N = 11,400) participants were assessed in 2006/2008, and the English Longitudinal Study of Ageing (ELSA, N = 7453) participants were assessed in 2010/2011 on personality and covariates. Dementia incidence was tracked for 14 years in the HRS and 8 years in ELSA. In both HRS and ELSA, higher neuroticism domain and nuances (particularly nervous and worry) were related to a higher risk of incident dementia, whereas higher conscientiousness domain and nuances (particularly responsibility and organization) were associated with a lower risk of dementia. To a lesser extent, higher extraversion (active), openness (broad-minded, curious, and imaginative), and agreeableness (helpful, warm, caring, and sympathetic) nuances were associated with a lower risk of dementia, with replicable effects across the two samples. A poly-nuance score, aggregating the effects of personality items, was associated with an increased risk of incident dementia in the HRS and ELSA, with effect sizes slightly stronger than those of the personality domains. Clinical, behavioral, psychological, and genetic covariates partially accounted for these associations. The present study provides novel and replicable evidence for specific personality characteristics associated with the risk of incident dementia., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Most Five-Factor Model (FFM) questionnaire items contain unique variance that is partly heritable, stable, and consensually observable, demonstrates consistent associations with age and sex, and predicts life outcomes beyond higher order factors. Extending these findings to the HEXACO model, we meta-analyzed single-item cross-rater agreement, heritability, and 2-year stability using samples from six countries. We analyzed raw item scores and their residual variance and adjusted the estimates for measurement unreliability. The median cross-rater agreement, heritability, and stability estimates were, respectively, .30, .30, and .57, for raw items and .10, .16, and .39, for item residuals. Adjusted for reliability, the respective medians were .46 and .25 for cross-rater agreement, .46 and .39 for heritability, and .87 and .94 for stability. These results are strikingly consistent with FFM-based findings, providing nondismissible evidence that single items index a partly unique level of the trait hierarchy-personality nuances -with trait properties comparable to those of higher-order traits., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: While our understanding of the single-cell gene expression patterns underlying the transformation of vascular cell types during the progression of atherosclerosis is rapidly improving, the clinical and pathophysiological relevance of these changes remains poorly understood., Methods: Single-cell RNA sequencing data generated with SmartSeq2 (≈8000 genes/cell) in 16 588 single cells isolated during atherosclerosis progression in Ldlr mice with human-like plasma lipoproteins and from humans with asymptomatic and symptomatic carotid plaques was clustered into multiple subtypes. For clinical and pathophysiological context, the advanced-stage and symptomatic subtype clusters were integrated with 135 tissue-specific (atherosclerotic aortic wall, mammary artery, liver, skeletal muscle, and visceral and subcutaneous, fat) gene-regulatory networks (GRNs) inferred from 600 coronary artery disease patients in the STARNET (Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task) study. -/- Apob 100/100 mice with human-like plasma lipoproteins and from humans with asymptomatic and symptomatic carotid plaques was clustered into multiple subtypes. For clinical and pathophysiological context, the advanced-stage and symptomatic subtype clusters were integrated with 135 tissue-specific (atherosclerotic aortic wall, mammary artery, liver, skeletal muscle, and visceral and subcutaneous, fat) gene-regulatory networks (GRNs) inferred from 600 coronary artery disease patients in the STARNET (Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task) study., Results: Advanced stages of atherosclerosis progression and symptomatic carotid plaques were largely characterized by 3 smooth muscle cells (SMCs), and 3 macrophage subtype clusters with extracellular matrix organization/osteogenic (SMC), and M1-type proinflammatory/Trem2-high lipid-associated (macrophage) phenotypes. Integrative analysis of these 6 clusters with STARNET revealed significant enrichments of 3 arterial wall GRNs: GRN33 (macrophage), GRN39 (SMC), and GRN122 (macrophage) with major contributions to coronary artery disease heritability and strong associations with clinical scores of coronary atherosclerosis severity. The presence and pathophysiological relevance of GRN39 were verified in 5 independent RNAseq data sets obtained from the human coronary and aortic artery, and primary SMCs and by targeting its top-key drivers, FRZB and ALCAM in cultured human coronary artery SMCs., Conclusions: By identifying and integrating the most gene-rich single-cell subclusters of atherosclerosis to date with a coronary artery disease framework of GRNs, GRN39 was identified and independently validated as being critical for the transformation of contractile SMCs into an osteogenic phenotype promoting advanced, symptomatic atherosclerosis., Competing Interests: Disclosures J.L.M. Björkegren and A. Ruusalepp are shareholders of Clinical Gene Networks AB (CGN) that has an invested interest in STARNET.

Study Design: This was a sub-group analysis of a multicentre, randomised, placebo-controlled, double-blind trial (ECLISP trial) OBJECTIVES: To assess the efficacy of a probiotic containing at least 6.5 × 10 9 live Lactobacillus casei Shirota (LcS) in preventing antibiotic associated diarrhoea (AAD) in patients with spinal cord injury (SCI) who consumed proton pump inhibitor (PPI) regularly. LcS or placebo was given once daily for the duration of an antibiotic course and continued for 7 days thereafter. The trial was registered with ISRCTN:13119162., Setting: Three SCI centres (National Spinal Injuries Centre, Midland Centre for Spinal Injuries and Princess Royal Spinal Cord Injuries Centre) in the United Kingdom METHODS: Between November 2014, and November 2019, 95 eligible consenting SCI patients (median age: 57; IQ range: 43-69) were randomly allocated to receive LcS (n = 50) or placebo (n = 45). The primary outcome is the occurrence of AAD up to 30 days after finishing LcS/placebo., Results: The LcS group had a significantly lower incidence of AAD at 30 days after finishing the antibiotic course (28.0 v 53.3%, RR: 95% CI: 0.53, 0.31-0.89; z = 2.5, p = 0.01). Multivariate logistic regression analysis identified that LcS can reduce the risk of AAD at 30 days (OR: 0.36, 95% CI 0.13, 0.99, p < 0.05). No intervention-related adverse events were reported during the study., Conclusions: LcS has the potential to prevent AAD in what could be considered a defined vulnerable group of SCI patients on regular PPI. A confirmatory, randomised, placebo-controlled study is needed to confirm this apparent therapeutic success to translate it into appropriate clinical outcomes., Sponsorship: Yakult Honsha Co., Ltd., (© 2024. Crown.)

Workers of social hymenopterans (ants, bees and wasps) display specific tasks depending on whether they are younger or older. The relative importance of behavior and age in modulating immune function has seldom been addressed. We compared the strength of encapsulation-melanization immune response (hereafter melanotic encapsulation) in paper wasps displaying age polyethism or experimentally prevented from behavioral specialization. Foragers of Polybia paulista had higher melanotic encapsulation than guards, regardless of their age. Nevertheless, melanotic encapsulation decreased with age when wasps were prevented from behavioral specialization. Thus, in this species, worker melanotic encapsulation seems more sensitive to task than age. Foraging is considered one of the riskier behaviors in terms of pathogen exposure, so upregulating melanotic encapsulation in foragers can possibly improve both individual and colony-level resistance against infections., 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 Elsevier Ltd. All rights reserved.)

The process of drying agricultural products for food preservation is a difficult task that requires a significant amount of energy. The increasing cost and depletion of fossil fuels have led to the development of a food dryer that utilizes renewable energy sources. This research paper proposes the design and performance evaluation of an indirectly forced convection desiccant integrated solar dryer (IFCDISD) at the Solar Energy Research Lab at USPCAS-E, NUST Pakistan. Tomatoes were chosen as the test product due to their importance and widespread consumption. The drying process involves slicing the tomatoes and placing them on the IFCDISD rack, where a desiccant called calcium chloride (CaCl 2 ) is integrated into the dryer. The experiments were conducted during both sunshine (SS) hours and Off-sunshine (OSS) hours. The IFCDISD operates using sunlight during SS hours and utilizes the absorbed heat of CaCl 2 in OSS hours via a forced DC brushless fan powered by battery charged thro solar panel. The tomatoes were weighed before and after each drying mode, and the moisture removal was calculated. The results show that the dryer efficiency was 50.14 % on day 1, 66 % on day 2, and an overall efficiency of 58.07 %. The moisture content removal was 42.858 % on day 1, 22.9979 % on day 2, and an overall moisture content removal of 58.07 %. Moreover, the payback period is 5.1396 and the carbon mitigation was recorded as 2.0335, and the earned carbon credit was recorded as 11559.6., Competing Interests: 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., (© 2024 The Authors.)

Objective: Deep brain stimulation (DBS) is an effective treatment for medically refractory movement disorders and other neurological conditions. To comprehensively characterize the prevalence, locations, timing of detection, clinical effects, and risk factors of DBS-related intracranial hemorrhage (ICH), the authors performed a systematic review of the published literature., Methods: PubMed, EMBASE, and Web of Science were searched using 2 concepts: cerebral hemorrhage and brain stimulation, with filters for English, human studies, and publication dates 1980-2023. The inclusion criteria were the use of DBS intervention for any human neurological condition, with documentation of hemorrhagic complications by location and clinical effect. Studies with non-DBS interventions, no documentation of hemorrhage outcome, patient cohorts of ≤ 10, and pediatric patients were excluded. The risk of bias was assessed using Centre for Evidence-Based Medicine Levels of Evidence. The authors performed proportional meta-analysis for ICH prevalence., Results: A total of 63 studies, with 13,056 patients, met the inclusion criteria. The prevalence of ICH was 2.9% (fixed-effects model, 95% CI 2.62%-3.2%) per patient and 1.6% (random-effects model, 95% CI 1.34%-1.87%) per DBS lead, with 49.6% being symptomatic. The ICH rates did not change with time. ICH most commonly occurred around the DBS lead, with 16% at the entry point, 31% along the track, and 7% at the target. Microelectrode recording (MER) during DBS was associated with increased ICH rate compared to DBS without MER (3.5 ± 2.2 vs 2.1 ± 1.4; p[T ≤ t] 1-tail = 0.038). Other reported ICH risk factors include intraoperative systolic blood pressure > 140 mm Hg, sulcal DBS trajectories, and multiple microelectrode insertions. Sixty percent of ICH was detected at 24 hours postoperatively and 27% intraoperatively. The all-cause mortality rate of DBS was 0.4%, with ICH accounting for 22% of deaths. Single-surgeon DBS experience showed a weak inverse correlation (r = -0.27, p = 0.2189) between the rate of ICH per lead and the number of leads implanted per year., Conclusions: This study provides level III evidence that MER during DBS is a risk factor for ICH. Other risk factors include intraoperative systolic blood pressure > 140 mm Hg, sulcal trajectories, and multiple microelectrode insertions. Avoidance of these risk factors may decrease the rate of ICH.

Introduction: Variation in access to parenteral nutrition (PN) in patients with intestinal failure secondary to malignant bowel obstruction (MBO) exists due to differing practice, beliefs and resource access. We aimed to examine differences in nutritional care pathways and outcomes, by referral to nutrition team for PN in patients with MBO., Methods: This is a retrospective cohort study of MBO adults admitted to eight UK hospitals within a year and 1 year follow-up. Demographic, nutritional and medical data were analysed by comparing patients referred (R) or not referred (NR) for PN. Differences between groups were tested by Kruskal-Wallis, Chi-Squared tests and multi-level regression and survival using Cox regression., Results: 232 patients with 347 MBO admissions [median 66yr, (IQR: 55-74yrs), 67 % female], 79/232 patients were referred for PN (R group). Underlying primary malignancies of gynaecological and gastrointestinal origin predominated (71 %) and 78 % with metastases. Those in the NR group were found to be older, weigh more on admission, and more likely to be treated conservatively compared to those in the R group. For 123 (35 %) admissions, patients were referred to a nutrition team, and for 204 (59 %) admissions, patients were reviewed by a dietician. Multi-disciplinary team discussion and dietetic contact were more likely to occur in the R group-123/347 admissions (R vs NR group: 27 % vs. 7 %, P = 0.001; 95 % vs 39 %, P < 0.0001). Median admission weight loss was 8 % (IQR: 0 to 14). 43/123 R group admissions received inpatient PN only, with 32 patients discharged or already established on home parenteral nutrition. Overall survival was 150 days (126-232) with no difference between R/NR groups., Conclusion: In this multi-centre study evaluating nutritional care management of patients with malignant bowel obstruction, only 1 in 3 admissions resulted in a referral to the nutrition team for PN, and just over half were reviewed by a dietician. Further prospective research is required to evaluate possible consequences of these differential care pathways on clinical outcomes and quality of life., Competing Interests: Declaration of competing interest Pinal Patel's Research Post was funded by Calea, Fresenius Kabi, UK., (Copyright © 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background: Cervical cancer is a preventable disease, despite being one of the most common types of female cancers worldwide. Integrating existing programs for cervical cancer screening with personalized risk prediction algorithms can improve population-level cancer prevention by enabling more targeted screening and contrive preventive healthcare innovations. While algorithms developed for cervical cancer risk prediction have shown promising performance in internal validation on more homogeneous populations, their ability to generalize to external populations remains to be assessed., Methods: To address this gap, we perform a cross-population comparative study of personalized prediction algorithms for more personalized cervical cancer screening. Using data from the Norwegian and Estonian populations, the algorithms are validated on internal and external datasets to study their potential biases and limitations when applied to different populations. We evaluate the algorithms in predicting progression from low-grade precancerous cervical lesions, simulating a clinically relevant application of more personalized risk stratification., Results: As expected, our numerical experiments show that algorithm performance varies depending on the population. However, some algorithms show strong generalization capacity across different data sources. Using Kaplan-Meier estimates, we demonstrate the strengths and limitations of the algorithms in detecting cancer progression over time by comparing to the trends observed from data. We assess their overall discrimination performance in personalized risk predictions by analyzing the accuracy and confidence in individual risk estimates., Discussion and Conclusion: This study examines the effectiveness of personalized prediction algorithms across different populations. Our results demonstrate the potential for generalizing risk prediction algorithms to external populations. These findings highlight the importance of considering population diversity when developing risk prediction algorithms., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Thiopurine S-methyltransferase (TPMT) is an important enzyme involved in the deactivation of thiopurines and represents a major determinant of thiopurine-related toxicities. Despite its well-known importance in thiopurine metabolism, the understanding of its endogenous role is lacking. In the present study, we aimed to gain insight into the molecular processes involving TPMT by applying a data fusion approach to analyze whole-genome expression data. The RNA profiling was done on whole blood samples from 1017 adult male and female donors to the Estonian biobank using Illumina HTv3 arrays. Our results suggest that TPMT is closely related to genes involved in oxidoreductive processes. The in vitro experiments on different cell models confirmed that TPMT influences redox capacity of the cell by altering S-adenosylmethionine (SAM) consumption and consequently glutathione (GSH) synthesis. Furthermore, by comparing gene networks of subgroups of individuals, we identified genes, which could have a role in regulating TPMT activity. The biological relevance of identified genes and pathways will have to be further evaluated in molecular studies., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest that are directly relevant to the content of this article., (Copyright © 2023. Published by Elsevier B.V.)

This study discusses findings from comparative case studies of the governance of health services purchasing agencies in 10 eastern European and central Asian countries established over the past 30 years, and the relationship between governance attributes, institutional development, and the progress made in strategic purchasing. The feasibility and effectiveness of implementing international recommendations from the health sector and wider public sector governance literature and practice are also discussed. The study finds that only those countries that have transitioned from middle to high-income status during the study period have been successful in comprehensively and consistently implementing internationally recommended practices. Moreover, these countries have made varying progress in developing capable purchasers with technical and operational independence, as well as advancing strategic purchasing. However, the current middle-income countries (MICs) in the study have implemented only certain elements of recommended governance practices, often superficially. Notably, the study reveals that some international recommendations, particularly those related to higher degrees of purchaser autonomy and the associated governance structures observed in western European social health insurance funds, have proven challenging to implement effectively or sustain in the MICs. None of the MICs succeeded in strategic purchasing beyond a limited agenda or scale, and even then, only implementing and sustaining them during favorable conditions. Difficulties in maintaining these achievements can be attributed, in part, to governance deficiencies. However, setbacks are commonly linked to periods of political and economic instability, which in turn lead to fluctuations in policy priorities, institutional instability, and inadequacies in health budgets. The study findings point to some actions related to civil society and stakeholder engagement, accountability frameworks, and digitalization in MICs that can facilitate continuity in health reforms and the functioning of purchasing institutions despite these challenges. The findings of the study provide important lessons for countries designing or newly implementing health purchasing agencies and for countries reviewing the performance and governance of their health purchasing agencies with a view to developing or strengthening strategic purchasing., Competing Interests: 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., (© 2023 Published by Elsevier B.V.)

Background: Although the persistence of physical symptoms after SARS-CoV-2 infection is a major public health concern, evidence from large observational studies beyond one year post diagnosis remain scarce. We aimed to assess the prevalence of physical symptoms in relation to acute illness severity up to more than 2-years after diagnosis of COVID-19., Methods: This multinational study included 64,880 adult participants from Iceland, Sweden, Denmark, and Norway with self-reported data on COVID-19 and physical symptoms from April 2020 to August 2022. We compared the prevalence of 15 physical symptoms, measured by the Patient Health Questionnaire (PHQ-15), among individuals with or without a confirmed COVID-19 diagnosis, by acute illness severity, and by time since diagnosis. We additionally assessed the change in symptoms in a subset of Swedish adults with repeated measures, before and after COVID-19 diagnosis., Findings: During up to 27 months of follow-up, 34.5% participants (22,382/64,880) were diagnosed with COVID-19. Individuals who were diagnosed with COVID-19, compared to those not diagnosed, had an overall 37% higher prevalence of severe physical symptom burden (PHQ-15 score ≥15, adjusted prevalence ratio [PR] 1.37 [95% confidence interval [CI] 1.23-1.52]). The prevalence was associated with acute COVID-19 severity: individuals bedridden for seven days or longer presented with the highest prevalence (PR 2.25 [1.85-2.74]), while individuals never bedridden presented with similar prevalence as individuals not diagnosed with COVID-19 (PR 0.92 [0.68-1.24]). The prevalence was statistically significantly elevated among individuals diagnosed with COVID-19 for eight of the fifteen measured symptoms: shortness of breath, chest pain, dizziness, heart racing, headaches, low energy/fatigue, trouble sleeping, and back pain. The analysis of repeated measurements rendered similar results as the main analysis., Interpretation: These data suggest an elevated prevalence of some, but not all, physical symptoms during up to more than 2 years after diagnosis of COVID-19, particularly among individuals suffering a severe acute illness, highlighting the importance of continued monitoring and alleviation of these targeted core symptoms., Funding: This work was mainly supported by grants from NordForsk (COVIDMENT, grant number 105668 and 138929) and Horizon 2020 (CoMorMent, 847776). See Acknowledgements for further details on funding., Competing Interests: OAA receives support from the NordForsk (grant number 105668 COVIDMENT) and the European Union’s Horizon 2020 Research and Innovation Programme (Grant 847776; CoMorMent). OAA declares receiving grants or contracts from NIH NIMN Award (R01MH123724-01, 1R01MH124839, 1R01MH129742, 1R01MH129858-01A1), Research Council of Norway (RCN grants 223273, 296030, 300309, 324252), the South-East Norway Health Authority (grant 2017-112, 2022-073), European Union’s Horizon 2020 Research and Innovation Programme (Grant 964874 REALMENT), EEA-RO-NO-2018-0535, and KG Jebsen Stiftelsen (grants SKGJ-MED-008 and SKGJ-MED-021). OAA receives consulting fees from Biogen, Cortechs.ai and Milken. OAA gets Speaker’s honorarium from Janssen, Lundbeck and Sunovion, and has a patent on Intranasal Administration (US20160310683 A1). OAA participated in advisory board as National PI for JANSSEN trial depression, MAPS trial PTSD and BI trial schizophrenia. OAA declares having stock at Cortechs.ai. RP receives grant of Excellence, Icelandic Research Fund. RP declares to be the vice president at UEMS Section of Internal Medicine, a board member of the Icelandic Society of Internal Medicine, and is the president of the Icelandic Transplantation Society. EF received a payment for keynote lecture from Astra Zeneca. SUJ is a leader in Metacognitive Therapy Institute Norwegian Branch. FF receives support from the NordForsk (grant number 105668 and 138929 COVIDMENT) and the Horizon 2020 (Grant 847776; CoMorMent). UAV receives support from the NordForsk (grant number 105668 and 138929 COVIDMENT) and the Horizon 2020 (Grant 847776; CoMorMent). AL declares to receive Fredrik and Ingrid Thuring Foundation. OBVP receives Independent Research Fund Denmark (0214-00127B). QS declares receiving support from the Outstanding Clinical Discipline Project of Shanghai Pudong (Grant No.: PWYgy2021-02) and the Fundamental Research Funds for the Central Universities. PFS declares receiving funding from the Swedish Research Council (Vetenskapsrådet, award D0886501). PFS also receives consulting fees, participating on a data safety monitoring board or advisory board, and holds stock or stock options, from Neumora Therapeutics. All other authors declare no competing interests., (© 2023 The Author(s).)

Background and Aims: The response of subarctic grassland's below-ground to soil warming is key to understanding this ecosystem's adaptation to future climate. Functionally different below-ground plant organs can respond differently to changes in soil temperature (Ts). We aimed to understand the below-ground adaptation mechanisms by analysing the dynamics and chemistry of fine roots and rhizomes in relation to plant community composition and soil chemistry, along with the duration and magnitude of soil warming., Methods: We investigated the effects of the duration [medium-term warming (MTW; 11 years) and long-term warming (LTW; > 60 years)] and magnitude (0-8.4 °C) of soil warming on below-ground plant biomass (BPB), fine root biomass (FRB) and rhizome biomass (RHB) in geothermally warmed subarctic grasslands. We evaluated the changes in BPB, FRB and RHB and the corresponding carbon (C) and nitrogen (N) pools in the context of ambient, Ts < +2 °C and Ts > +2 °C scenarios., Key Results: BPB decreased exponentially in response to an increase in Ts under MTW, whereas FRB declined under both MTW and LTW. The proportion of rhizomes increased and the C-N ratio in rhizomes decreased under LTW. The C and N pools in BPB in highly warmed plots under MTW were 50 % less than in the ambient plots, whereas under LTW, C and N pools in warmed plots were similar to those in non-warmed plots. Approximately 78 % of the variation in FRB, RHB, and C and N concentration and pools in fine roots and rhizomes was explained by the duration and magnitude of soil warming, soil chemistry, plant community functional composition, and above-ground biomass. Plant's below-ground biomass, chemistry and pools were related to a shift in the grassland's plant community composition - the abundance of ferns increased and BPB decreased towards higher Ts under MTW, while the recovery of below-ground C and N pools under LTW was related to a higher plant diversity., Conclusion: Our results indicate that plant community-level adaptation of below ground to soil warming occurs over long periods. We provide insight into the potential adaptation phases of subarctic grasslands., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: MicroRNAs (miRNAs) are key regulators of gene expression that have been implicated in gynecological and breast cancers. Understanding the cancer stage-wise expression patterns of miRNAs and their interactions with other RNA molecules in cancer is crucial to improve cancer diagnosis and treatment planning. Comprehensive web tools that integrate data on the transcriptome, circulating miRNAs, and their validated targets to derive beneficial conclusions in cancer research are lacking., Methods: Using the Shiny R package, we developed a web tool called ExplORRNet that integrates transcriptomic profiles from The Cancer Genome Atlas and miRNA expression data derived from various sources, including tissues, cell lines, exosomes, serum, and plasma, available in the Gene Expression Omnibus database. Differential expression analyses between normal and tumor tissue samples as well as different stages of cancer, accompanied by gene enrichment and survival analyses, can be performed using specialized R packages. Additionally, a miRNA-messenger RNA (mRNA)-long non-coding RNA (lncRNA) networks are constructed to identify regulatory modules., Results: Our tool identifies cancer stage-wise differentially regulated miRNAs, mRNAs, and lncRNAs in gynecological and breast cancers. Survival analysis identifies miRNAs associated with patient survival, and functional enrichment analysis provides insights into dysregulated miRNA-related biological processes and pathways. The miRNA-mRNA-lncRNA networks highlight interconnected regulatory molecular modules driving cancer progression. Case studies demonstrate the utility of the ExplORRNet for studying gynecological and breast cancers., Conclusion: ExplORRNet is an intuitive and user-friendly web tool that provides a deeper understanding of dysregulated miRNAs and their functional implications in gynecological and breast cancers. We hope our ExplORRNet tool has potential utility among the clinical and basic researchers and will be beneficial to the entire cancer genomics community to encourage and facilitate mining the rapidly growing public databases to progress the field of precision oncology. The ExplORRNet is available at https://mirna.cs.ut.ee., Competing Interests: 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., (© 2023 The Authors.)

This study is about how lay persons perceive and represent artificial intelligence in general as well as its use in weaponised autonomous ground vehicles in the military context. We analysed the discourse of six focus groups in Estonia, using an automatic text analysis tool and complemented the results by a qualitative thematic content analysis. The findings show that representations of artificial intelligence-driven machines are anchored in the image of man. A cluster analysis revealed five dominant themes: artificial intelligence as programmed machines, artificial intelligence and the problem of control, artificial intelligence and its relation to human life, artificial intelligence used in wars and ethical problems in developing autonomous weaponised machines. The findings are discussed with regard to people's tendency to anthropomorphise robots despite their lack of emotions, which can be seen as a last resort when confronting an autonomous machine where the usual interpersonal understanding of intentions does not apply., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

The aim of this study was to evaluate how schizophrenia spectrum disorders (SSD) and applied long-term (5.1 years) antipsychotic (AP) treatment affect the serum levels of tryptophan (Trp) metabolites. A total of 112 adults (54 first-episode psychosis [FEP] patients and 58 control subjects [CSs]) participated in the study. The investigated changes in the metabolite levels appeared against a background of persistent increase in BMI and waist circumference among the patients. Regarding the kynurenine (KYN) pathway, the strongest changes were seen in AP-naïve FEP patients. Trp, KYN, kynurenic acid (KYNA), and anthranilic acid (ANT) levels were significantly reduced in blood samples from patients in the early stage of the disease. Furthermore, 3-OH-kynurenine (3-HK) and quinolinic acid (QUIN) levels were somewhat lower in these patients. Most of these changes in the KYN pathway became weaker with AP treatment. The levels of serotonin and its metabolite 5-HIAA tended to be higher at 5.1 years in patients showing the relation of elevated serotonin turnover to increased BMI and waist circumference. The similar trend was evident for the ratio between xanthurenic acid (XA) and KYNA with strong link to the elevated BMI. Altogether, the present study supports the role of Trp-metabolites in the development of obesity and metabolic syndrome in SSD patients., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

PHARMACOM-EPI is a novel framework to predict plasma concentrations of drugs at the time of occurrence of clinical outcomes. In early 2021, the U.S. Food and Drug Administration (FDA) issued a warning on the antiseizure drug lamotrigine claiming that it has the potential to increase the risk of arrhythmias and related sudden cardiac death due to a pharmacological sodium channel-blocking effect. We hypothesized that the risk of arrhythmias and related death is due to toxicity. We used the PHARMACOM-EPI framework to investigate the relationship between lamotrigine's plasma concentrations and the risk of death in older patients using real-world data. Danish nationwide administrative and healthcare registers were used as data sources and individuals aged 65 years or older during the period 1996 - 2018 were included in the study. According to the PHARMACOM-EPI framework, plasma concentrations of lamotrigine were predicted at the time of death and patients were categorized into non-toxic and toxic groups based on the therapeutic range of lamotrigine (3-15 mg/L). Over 1 year of treatment, the incidence rate ratio (IRR) of all-cause mortality was calculated between the propensities score matched toxic and non-toxic groups. In total, 7286 individuals were diagnosed with epilepsy and were exposed to lamotrigine, 432 of which had at least one plasma concentration measurement The pharmacometric model by Chavez et al. was used to predict lamotrigine's plasma concentrations considering the lowest absolute percentage error among identified models (14.25 %, 95 % CI: 11.68-16.23). The majority of lamotrigine associated deaths were cardiovascular-related and occurred among individuals with plasma concentrations in the toxic range. The IRR of mortality between the toxic group and non-toxic group was 3.37 [95 % CI: 1.44-8.32] and the cumulative incidence of all-cause mortality exponentially increased in the toxic range. Application of our novel framework PHARMACOM-EPI provided strong evidence to support our hypothesis that the increased risk of all-cause and cardiovascular death was associated with a toxic plasma concentration level of lamotrigine among older lamotrigine users., Competing Interests: Declaration of Competing Interest All authors declare that there is no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Conspiracy theories have accompanied vaccination since its mass introduction, circulating, among other forms, in humour - such as cartoons, and now, memes. Importantly, humour has targeted both vaccination and anti-vaccination stances. In this study, we discuss the peculiarities of humorous content within the vaccination debate and uncover the most popular thematic categories, forms and logical mechanisms of humour. We show that humorous and serious discussions on vaccination go hand-in-hand, but playfulness and ambiguity of humour complicate public understanding of the vaccination debate. Our analysis shows that vaccination humour often simplifies the complex issue of vaccination and makes it more understandable and more tangible for a broad audience.

The coronavirus disease 2019 (COVID-19) pandemic has generated high interest in factors modulating risk of infection, disease severity and recovery. Vitamin D has garnered interest since it is known to modulate immune function and vitamin D deficiency is associated with increased risk of respiratory infections and adverse health outcomes in severely ill patients. There are no population representative data on the direct relationship between vitamin D status and severe acute respiratory syndrome coronavirus 2 infection risk and severity of COVID-19. Data from intervention studies are limited to four studies. Here we summarise findings regarding vitamin D status and metabolism and their alterations during severe illness, relevant to COVID-19 patients. Further, we summarise vitamin D intervention studies with respiratory disease outcomes and in critically ill patients and provide an overview of relevant patient and population guidelines. Vitamin D deficiency is highly prevalent in hospitalised patients, particularly when critically ill, including those with COVID-19. Acute and critical illness leads to pronounced changes in vitamin D metabolism and status, suggestive of increased requirements. This needs to be considered in the interpretation of potential links between vitamin D status and disease risk and severity and for patient management. There is some evidence that vitamin D supplementation decreases the risk of respiratory tract infections, while supplementation of intensive care unit patients has shown little effect on disease severity or length of treatment. Considering the high prevalence of deficiency and low risks associated with supplementation, pro-actively applying current population and patient management guidelines to prevent, monitor and correct vitamin D deficiency is appropriate.

Recent evidence indicates that a word's paradigmatic neighbors affect production. However, these findings have mostly been obtained in careful laboratory settings using words in isolation, and thus ignoring potential effects that may arise from the syntagmatic context, which is typically present in spontaneous speech. The current corpus analysis investigates paradigmatic and syntagmatic effects in Estonian spontaneous speech. Following work on English, we focus on the duration of inflected and uninflected word-final /-s/ in content words, while simultaneously investigating whole words. Our analyses reveal three points. First, we find an effect of realized inflectional paradigm size, such that smaller paradigms actively used by the speakers lead to longer durations. Second, higher conditional probability is associated with shorter word forms and shorter segments. Finally, we do not directly replicate previous work on effects of inflectional status as in English word-final /-s/. Instead, we find that inflectional status interacts with conditional probability. We discuss the results in light of models of speech production and how they account for morphologically complex words and their paradigmatic neighbors.

In order to achieve visionary concepts such as Society 5.0 and Industry 5.0, there is a growing need for people who are able to create innovative robotic technologies. Training students to become such skilled professionals requires transitioning from often toy-like educational platforms with significant hardware limitations to costly research robots with full ROS (Robot Operating System) support. To aid in this transition, we propose Robotont - an open-source omnidirectional mobile robot platform with both physical hardware and a digital twin. Robotont enables robotics education with professional tools as well as provides researchers with a capable mobility platform for validating and demonstrating scientific results. Robotont has successfully been used for university teaching, professional education, and online courses about ROS and robotics., Competing Interests: 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., (© 2023 The Author(s).)

Neural network language models, such as BERT, can be used for information extraction from medical texts with unstructured free text. These models can be pre-trained on a large corpus to learn the language and characteristics of the relevant domain and then fine-tuned with labeled data for a specific task. We propose a pipeline using human-in-the-loop labeling to create annotated data for Estonian healthcare information extraction. This method is particularly useful for low-resource languages and is more accessible to those in the medical field than rule-based methods like regular expressions.

Electronically stored medical records offer a rich source of data for investigating treatment trajectories and identifying best practices in healthcare. These trajectories, which consist of medical interventions, give us a foundation to evaluate the economics of treatment patterns and model the treatment paths. The aim of this work is to introduce a technical solution for the aforementioned tasks. The developed tools use the open source Observational Health Data Sciences and Informatics Observational Medical Outcomes Partnership Common Data Model to construct treatment trajectories and implement these to compose Markov models for composing financial analysis between standard of care and alternatives.

Occasionally, a solution or idea arrives as a sudden understanding - an insight. Insight has been considered an "extra" ingredient of creative thinking and problem-solving. Here we propose that insight is central in seemingly distinct areas of research. Drawing on literature from a variety of fields, we show that besides being commonly studied in problem-solving literature, insight is also a core component in psychotherapy and meditation, a key process underlying the emergence of delusions in schizophrenia, and a factor in the therapeutic effects of psychedelics. In each case, we discuss the event of insight and its prerequisites and consequences. We review evidence for the commonalities and differences between the fields and discuss their relevance for capturing the essence of the insight phenomenon. The goal of this integrative review is to bridge the gap between the different views and inspire interdisciplinary research efforts for understanding this central process of human cognition., 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 Elsevier Inc. All rights reserved.)