Activation of Wnt/ß-catenin signaling is critical for the tumorigenesis of choroid plexus.

BACKGROUND: Choroid plexus (ChP) is the secretory epithelial structure located in brain ventricles. Choroid plexus tumors (CPTs) are rare neoplasms predominantly occurring in young patients with intensified malignancy in children. CPT treatment is hindered by insufficient knowledge of the tumor pathology and limited availability of valid models. METHODS: Genomic and transcriptomic data from CPT patients were analyzed to identify the putative pathological pathway. Cellular and molecular techniques were employed to validate bioinformatic results in CPT patient samples. Pharmacologic inhibition of Wnt/ß-catenin signaling was assessed in CPT cells. Cell-based assays of ChP cell lines were performed following CRISPR-Cas9-derived knockout and over-expression of Wnt/ß-catenin pathway genes. 3D CPT model was generated through CRISPR-Cas9-derived knockout of APC. RESULTS: We discovered that Wnt/ß-catenin signaling is activated in human CPTs, likely as a consequence of large-scale chromosomal instability events of the CPT genomes. We demonstrated that CPT-derived cells depend on autocrine Wnt/ß-catenin signaling for survival. Constitutive Wnt/ß-catenin pathway activation, either through knock-out of the negative regulator APC or overexpression of the ligand WNT3A, induced tumorigenic properties in ChP 2D in vitro models. Increased activation of Wnt/ß-catenin pathway in ChP organoids, through treatment with a potent GSK3ß inhibitor, reduced the differentiation of mature ChP epithelia cells. Remarkably, the depletion of APC was sufficient to induce the oncogenic transformation of ChP organoids. CONCLUSIONS: Our research identifies Wnt/ß-catenin signaling as a critical driver of CPT tumorigenesis and provides the first 3D in vitro model for future pathological and therapeutic studies of CPT.

Study protocol for a single-blind, parallel-group, randomized, controlled superiority trial of intensive versus weekly delivered prolonged exposure for adults with post-traumatic stress disorder.

BACKGROUND: Prolonged exposure (PE) therapy is widely recognized as an effective treatment for post-traumatic stress disorder (PTSD) and is often considered one of the primary options for addressing this condition. Nevertheless, a significant proportion of patients (30-51%) fail to demonstrate clinically significant symptom changes. One of the reasons is that a high proportion of patients drop out from treatment, which often lasts for a minimum of 3-4 months. Hence, there is an urgent need for PTSD treatments that can be delivered to decrease dropout rates. A more intensive PE treatment approach has been suggested to decrease dropout rates and in addition achieve faster recovery rates and has shown promising effects on reducing PTSD symptoms but needs to be tested against firsthand treatment. METHODS: This single-blind, randomized controlled trial (N = 140) will compare an intensive delivery format of prolonged exposure (iPE) against standard weekly delivered sessions of PE. The primary outcome is change on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). Secondary outcomes include self-rated measures of symptoms of PTSD and complex PTSD, depression and quality of life, speed of recovery, cost effectiveness, dropout rates, and adverse events. DISCUSSION: This study will be the first to compare iPE with first-line treatment in a psychiatric outpatient setting. One of the key strengths of this study lies in its implementation within a clinical setting and the broad eligibility criteria. Additionally, the utilization of gold-standard assessment measures ensures the accuracy and reliability of the outcomes. However, several potential challenges may arise during the study's execution. These challenges may include difficulties in participant recruitment, ensuring adequate participant retention, adherence to the treatment protocol, and maintaining therapist retention mostly due to recruitment taking place at one single clinic. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT05934175. Registered on June 6, 2023. Open Science Framework (OSF) https://osf.io/7qsb3 . Registered on September 2, 2023.

Characterisation of circulating tumor-associated and immune cells in patients with advanced-stage non-small cell lung cancer.

Objectives: Globally, non-small cell lung cancer (NSCLC) is the most prevalent form of lung cancer and the leading cause of cancer-related deaths. Tumor-associated circulating cells in NSCLC can have a wide variety of morphological and phenotypic characteristics, including epithelial, immunological or hybrid subtypes. The distinctive characteristics and potential clinical significance of these cells in patients with NSCLC are explored in this study. Methods: We utilised a spiral microfluidic device to enrich large cells and cell aggregates from the peripheral blood samples of NSCLC patients. These cells were characterised through high-resolution immunofluorescent imaging and statistical analysis, correlating findings with clinical information from our patient cohort. Results: We have identified varied populations of heterotypic circulating tumor cell clusters with differing immune cell composition that included a distinct class of atypical tumor-associated macrophages that exhibits unique morphology and cell size. This subtype's prevalence is positively correlated with the tumor stage, progression and metastasis. Conclusions: Our study reveals a heterogeneous landscape of circulating tumor cells and their clusters, underscoring the complexity of NSCLC pathobiology. The identification of a unique subtype of atypical tumor-associatedmacrophages that simultaneously express both tumor and immune markers and whose presence correlates with late disease stages, poor clinical outcomes and metastatic risk infers  the potential of these cells as biomarkers for NSCLC staging and prognosis. Future studies should focus on the role of these cells in the tumor microenvironment and their potential as therapeutic targets. Additionally, longitudinal studies tracking these cell types through disease progression could provide further insights into their roles in NSCLC evolution and response to treatment.

Investigating the added effects of guidance in digital psychological self-care for alcohol problems (ALVA)-protocol for a randomized factorial optimization trial.

BACKGROUND: The continual development and implementation of effective digital interventions is one important strategy that may serve to bridge the well-known treatment gap related to problematic alcohol use. Research suggests that clinician guidance, provided in different ways during the digital intervention (i.e., written weekly messages, phone calls etc.), can boost intervention engagement and effects. Digital psychological self-care (DPSC) is a new delivery format wherein an unguided digital intervention is provided within the framework of a structured care process that includes initial clinical assessment and follow-up interviews. In a recent feasibility study, a DPSC intervention for problematic alcohol use, ALVA, provided without any extra guidance, was found safe and credible and to have promising within-group effects on alcohol consumption. The aim of the current study is to gather information on the effects and efficiency of different forms of guidance added to ALVA, in order to optimize the intervention. METHODS: This protocol describes a randomized factorial trial where the effects of two different ways of providing guidance (mid-treatment interview, weekly written messages, respectively) in DPSC for problematic alcohol use are investigated. Optimization criteria will be applied to the results regarding how effective the intervention is at reducing alcohol consumption measured by the number of standard drinks per week together with the clinician time spent on guidance. DISCUSSION: This study will investigate the added benefit of different forms of guidance to DPSC for problematic alcohol use. These added effects will be compared to the added cost of guidance, according to pre-defined optimization criteria. TRIAL REGISTRATION: Clinicaltrials.gov: NCT05649982. Registered on 06 December 2022. Prospectively registered.

A virtual reality platform to evaluate the effects of supernumerary limbs' appearance.

Supernumerary robot limbs (SL) can expand the ability of users by increasing the number of degrees of freedom that they control. While several SLs have been designed and tested on human participants, the effect of the limb's appearance on the user's acceptance, embodiment and device usage is not yet understood. We developed a virtual reality platform with a three-arm avatar that enabled us to systematically investigate the effect of the supernumerary limb's appearance on their perception and motion control performance. A pilot study with 14 participants exhibited similar performance, workload and preference in human-like or robot-like appearance with a trend of preference for the robotic appearance.

Dissociating haptic feedback from physical assistance does not improve motor performance.

In robots for motor rehabilitation and sports training, haptic assistance typically provides both mechanical guidance and task-relevant information. With the natural human tendency to minimise metabolic cost, mechanical guidance may however prevent efficient short term learning and retention. In this work, we explore the effect of providing haptic feedback to the not active hand during a tracking task. We test four types of haptic feedback: task- or error-related information, no information and irrelevant information. The results show that feedback provided to the hand not carrying out the tracking task did not improve task performance. However, irrelevant information to the task worsened performance, and negatively influenced the participants' perception of helpfulness, assistance, likability and predictability.

Study protocol for a single-blind, parallel-group, randomised, controlled non-inferiority trial of 4-day intensive versus standard cognitive behavioural therapy for adults with obsessive-compulsive disorder.

INTRODUCTION: Individual cognitive behavioural therapy (CBT) with exposure and response prevention is an effective treatment for obsessive-compulsive disorder (OCD). However, individual CBT is costly and time-consuming, requiring weekly therapy sessions for 3-4 months. A 4-day intensive version of CBT for OCD delivered in group format has been recently developed in Norway (Bergen 4-day treatment, B4DT). B4DT has shown promising results in several uncontrolled and one small, randomised trial, but its non-inferiority to the gold standard treatment has not been established. METHODS AND ANALYSIS: This single-blind, randomised controlled trial including 120 patients (60 per arm) will compare B4DT to individual CBT. The primary outcome is the blind assessor-rated Yale-Brown Obsessive Compulsive Scale (Y-BOCS). We hypothesise that B4DT will be non-inferior to gold standard CBT 15 weeks after treatment start. The non-inferiority margin is set at four points on the Y-BOCS. Secondary outcomes include time to treatment response, cost-effectiveness, response and remission rates, drop-out rates and adverse events. ETHICS AND DISSEMINATION: This study has been approved by the Swedish Ethical Review Authority. Hypotheses were specified and analysis code published before data collection started. Results from all analyses will be reported in accordance with the Consolidated Standards of Reporting Trials statement for non-pharmacological trials and Consolidated Health Economic Evaluation Reporting Standards irrespective of outcome. TRIAL REGISTRATION NUMBER: NCT05608278.

Increasing the Motivation to Train Through Haptic Social Interaction - Pilot study.

Motivation is crucial in stroke rehabilitation, as it enhances patient engagement, adherence, and recovery. Robots can be employed to improve motivation through multiplayer rehabilitation games, which allow patients to collaborate and interact in a virtual environment through multimodal sensory cues. This social interaction can provide social support and increase motivation, resulting in better therapy engagement. A hand rehabilitation robot (PLUTO) was used to investigate the potential of social interaction to implement haptic multiplayer games. Twelve unimpaired participants (6 dyads) played in solo, collaborative, and competitive game modes. Surprisingly, no difference was found in self-reported engagement, tension, or competence between solo and multiplayer games. However, the IMI scale indicated that engagement for multiplayer games was rated higher than for solo games. The collaborative game was preferred by 10 out of 12 participants, highlighting its potential for promoting behavioural involvement and engagement. This study indicates that using PLUTO with multiplayer game modes can enhance therapy engagement. This can potentially improve rehabilitation outcomes if translated to the patient population.

Translating and adapting the Alcohol Use Disorders Identification Test (AUDIT) for use in the Russian Federation: A multicentre pilot study to inform validation procedures.

Aims: The Alcohol Use Disorders Identification Test (AUDIT) is one of the most widely used screening instruments worldwide. Although it was translated into many languages, not many country-specific adaptations exist, and a formal validation procedure of the Russian version has been carried out only recently. The present contribution documents the different steps taken to formally translate and adapt a Russian-specific version of the AUDIT (RUS-AUDIT). Methods: The AUDIT was translated into Russian following an established protocol, revised and adapted to the country context using an expert panel, and field-tested in an iterative approach, in line with WHO rules on instrument translation and adaptation A total of three pilot phases were carried out on 134 patients from primary healthcare (PHC) and 33 patients from specialised alcohol treatment facilities (narcology), guided by a specially established advisory board. Changes in each version were informed by the findings of the previous pilot phase and a thorough panel discussion. Results: Based on the findings of three different pilot phases, the RUS-AUDIT was developed as a paper-and-pencil interview for PHC professionals. Since various issues with representation and counting of standard drinks for the second test item arose, a special show card was developed to support the assessment. Preliminary AUDIT-C scores indicated that more than one-third of the screened women (34.2%) and about half of the screened men (50.9%) from PHC facilities have exceeded risk thresholds. Conclusions: The RUS-AUDIT was constructed as a feasible assessment tool for interviewers and patients. The large number of PHC patients who exceed the risk threshold has corroborated the need for formal validation and Russia-specific cut-off scores, considering the specific drinking patterns.

Swedish multimodal cohort of patients with anxiety or depression treated with internet-delivered psychotherapy (MULTI-PSYCH).

PURPOSE: Depression and anxiety afflict millions worldwide causing considerable disability. MULTI-PSYCH is a longitudinal cohort of genotyped and phenotyped individuals with depression or anxiety disorders who have undergone highly structured internet-based cognitive-behaviour therapy (ICBT). The overarching purpose of MULTI-PSYCH is to improve risk stratification, outcome prediction and secondary preventive interventions. MULTI-PSYCH is a precision medicine initiative that combines clinical, genetic and nationwide register data. PARTICIPANTS: MULTI-PSYCH includes 2668 clinically well-characterised adults with major depressive disorder (MDD) (n=1300), social anxiety disorder (n=640) or panic disorder (n=728) assessed before, during and after 12 weeks of ICBT at the internet psychiatry clinic in Stockholm, Sweden. All patients have been blood sampled and genotyped. Clinical and genetic data have been linked to several Swedish registers containing a wide range of variables from patient birth up to 10 years after the end of ICBT. These variable types include perinatal complications, school grades, psychiatric and somatic comorbidity, dispensed medications, medical interventions and diagnoses, healthcare and social benefits, demographics, income and more. Long-term follow-up data will be collected through 2029. FINDINGS TO DATE: Initial uses of MULTI-PSYCH include the discovery of an association between PRS for autism spectrum disorder and response to ICBT, the development of a machine learning model for baseline prediction of remission status after ICBT in MDD and data contributions to genome wide association studies for ICBT outcome. Other projects have been launched or are in the planning phase. FUTURE PLANS: The MULTI-PSYCH cohort provides a unique infrastructure to study not only predictors or short-term treatment outcomes, but also longer term medical and socioeconomic outcomes in patients treated with ICBT for depression or anxiety. MULTI-PSYCH is well positioned for research collaboration.

Comparative studies of X chromosomes in Cervidae family.

The family Cervidae is the second most diverse in the infraorder Pecora and is characterized by variability in the diploid chromosome numbers among species. X chromosomes in Cervidae evolved through complex chromosomal rearrangements of conserved segments within the chromosome, changes in centromere position, heterochromatic variation, and X-autosomal translocations. The family Cervidae consists of two subfamilies: Cervinae and Capreolinae. Here we build a detailed X chromosome map with 29 cattle bacterial artificial chromosomes of representatives of both subfamilies: reindeer (Rangifer tarandus), gray brocket deer (Mazama gouazoubira), Chinese water deer (Hydropotes inermis) (Capreolinae); black muntjac (Muntiacus crinifrons), tufted deer (Elaphodus cephalophus), sika deer (Cervus nippon) and red deer (Cervus elaphus) (Cervinae). To track chromosomal rearrangements during Cervidae evolution, we summarized new data, and compared them with available X chromosomal maps and chromosome level assemblies of other species. We demonstrate the types of rearrangements that may have underlined the variability of Cervidae X chromosomes. We detected two types of cervine X chromosome-acrocentric and submetacentric. The acrocentric type is found in three independent deer lineages (subfamily Cervinae and in two Capreolinae tribes-Odocoileini and Capreolini). We show that chromosomal rearrangements on the X-chromosome in Cervidae occur at a higher frequency than in the entire Ruminantia lineage: the rate of rearrangements is 2 per 10 million years.

Digital psychological self-care for problematic alcohol use: feasibility of a new clinical concept.

BACKGROUND: Digital interventions based on cognitive-behavioural therapy and relapse prevention can increase treatment access for people with problematic alcohol use, but for these interventions to be cost-effective, clinician workload needs to remain low while ensuring patient adherence and effects. Digital psychological self-care is the provision of a self-guided digital intervention within a structured care process. AIMS: To investigate the feasibility and preliminary effects of digital psychological self-care for reducing alcohol consumption. METHOD: Thirty-six adults with problematic alcohol use received digital psychological self-care during 8 weeks, including telephone assessments as well as filling out self-rated questionnaires, before, directly after and 3 months after the intervention. Intervention adherence, usefulness, credibility and use of clinician time were assessed, along with preliminary effects on alcohol consumption. The study was prospectively registered as a clinical trial (NCT05037630). RESULTS: Most participants used the intervention daily or several times a week. The digital intervention was regarded as credible and useful, and there were no reported adverse effects. Around 1 h of clinician time per participant was spent on telephone assessments. At the 3-month follow-up, preliminary within-group effects on alcohol consumption were moderate (standardised drinks per week, Hedge's g = 0.70, 95% CI = 0.19-1.21; heavy drinking days, Hedge's g = 0.60, 95% CI = 0.09-1.11), reflecting a decrease from 23 to 13 drinks per week on average. CONCLUSIONS: Digital psychological self-care for reducing alcohol consumption appears both feasible and preliminarily effective and should be further optimised and studied in larger trials.

Effectiveness of Internet-based cognitive-behavioural therapy for obsessive-compulsive disorder (OCD-NET) and body dysmorphic disorder (BDD-NET) in the Swedish public health system using the RE-AIM implementation framework.

Objectives: Therapist-guided internet-delivered cognitive behaviour therapy (ICBT) is an efficacious treatment for obsessive-compulsive disorder (OCD) and body dysmorphic disorder (BDD), but it is unclear if the results obtained in controlled trials can be reproduced in clinical settings. We evaluated the implementation of ICBT for OCD (OCD-NET) and BDD (BDD-NET) in the Swedish public health system. Methods: Consecutive referrals to an outpatient psychiatric clinic providing ICBT, with a primary diagnosis of OCD or BDD, were included in the study. Four hundred and thirty-four participants started OCD-NET and 163 started BDD-NET. The primary outcome measures were the Yale Brown Obsessive Compulsive Scale (Y-BOCS) and the Y-BOCS for BDD (BDD-YBOCS), respectively. Participants were assessed before treatment, weekly during treatment, and after treatment. The study used the RE-AIM implementation framework, and the elements of reach, effectiveness, adoption, and implementation for the evaluation. Results: Intention to treat analysis of the OCD-NET sample (n = 434) showed a significant decrease in OCD symptoms from pre-treatment to post-treatment (mean reduction = -8.77 [95 % CI -9.48 to -8.05] p < .001, d = 1.94 [95 % CI 1.75 to 2.13]). Forty-nine percent (95 % CI 43 % to 56 %) of the participants in OCD-NET were classified as treatment responders and 21 % (95 % CI 16 % to 27 %) were in remission. Participants in BDD-NET (n = 163) also showed a significant decrease in BDD symptoms from pre-post treatment (mean reduction = -11.37 [95 % CI -12.9 to -9.87] p < .001, d = 2.07 [95 % CI 1.74 to 2.40]) and 69 % (95 % CI 58 % to 79 %) of the participants were classified as treatment responders and 48 % (95 % CI 38 % to 58 %) were in full or partial remission. Eighty-seven percent of the participants in OCD-NET and 78 % in BDD-NET were treatment completers and participants in both treatment groups reported a high treatment satisfaction at post treatment (OCD-NET = 87 %, BDD-NET = 79 %). The most reported negative effects attributed to the treatments were transient experiences of unpleasant feelings (52 %) and anxiety (50 %). The implementation also influenced treatment delivery and dramatically decreased the mean number of patients waiting to receive face-to-face treatment at the clinic. Conclusions: Our results indicate that OCD-NET and BDD-NET are suitable treatments for implementation in a Swedish public health service.

Characterization of exhaustion disorder and identification of outcomes that matter to patients: Qualitative content analysis of a Swedish national online survey.

Fatigue is a common presenting problem in healthcare settings, often attributed to chronic psychosocial stress. Understanding of fatigue and development of evidence-based treatments is hampered by a lack of consensus regarding diagnostic definitions and outcomes to be measured in clinical trials. This study aimed to map outcome domains of importance to the Swedish diagnosis stress-induced exhaustion disorder (ED; ICD-10, code F43.8 A). An online survey was distributed nationwide in Sweden to individuals who reported to have been diagnosed with ED and to healthcare professionals working with ED patients. To identify outcome domains, participants replied anonymously to four open-ended questions about symptoms and expectations for ED-treatment. Qualitative content analysis was conducted of a randomized subsample of respondents, using a mathematical model to determine data saturation. Six hundred seventy participants (573 with reported ED, 97 healthcare professionals) completed the survey. Qualitative content analysis of answers supplied by 105 randomized participants identified 87 outcomes of importance to ED encompassing physical, cognitive, and emotional symptoms as well as functional disability. Self-rating scales indicated that many ED participants, beyond reporting fatigue, also reported symptoms of moderate to severe depression, anxiety, insomnia, poor self-rated health, and sickness behavior. This study presents a map of outcome domains of importance for ED. Results shed light on the panorama of issues that individuals with ED deal with and can be used as a step to further understand the condition and to reach consensus regarding outcome domains to measure in clinical trials of chronic stress and fatigue. Preregistration: Open Science Framework (osf.io) with DOI https://doi.org/10.17605/OSF.IO/4VUAG.

Small-bowel capsule endoscopy in patients with Meckel's diverticulum: clinical features, diagnostic workup, and findings. A European multicenter I-CARE study.

BACKGROUND AND AIMS: Meckel's diverticulum (MD) may remain silent or be associated with adverse events such as GI bleeding. The main aim of this study was to evaluate indicative small-bowel capsule endoscopy (SBCE) findings, and the secondary aim was to describe clinical presentation in patients with MD. METHODS: This retrospective European multicenter study included patients with MD undergoing SBCE from 2001 until July 2021. RESULTS: Sixty-nine patients with a confirmed MD were included. Median age was 32 years with a male-to-female ratio of approximately 3:1. GI bleeding or iron-deficiency anemia was present in nearly all patients. Mean hemoglobin was 7.63 ± 1.8 g/dL with a transfusion requirement of 52.2%. Typical capsule endoscopy (CE) findings were double lumen (n = 49 [71%]), visible entrance into the MD (n = 49 [71%]), mucosal webs (n = 30 [43.5%]), and bulges (n = 19 [27.5%]). Two or more of these findings were seen in 48 patients (69.6%). Ulcers were detected in 52.2% of patients (n = 36). In 63.8% of patients (n = 44), a combination of double lumen and visible entrance into the MD was evident, additionally revealing ulcers in 39.1% (n = 27). Mean percent SB (small bowel) transit time for the first indicative image of MD was 57% of the total SB transit time. CONCLUSIONS: Diagnosis of MD is rare and sometimes challenging, and a preoperative criterion standard does not exist. In SBCE, the most frequent findings were double-lumen sign and visible diverticular entrance, sometimes together with ulcers.

How virtual and mechanical coupling impact bimanual tracking.

Bilateral training systems look to promote the paretic hand's use in individuals with hemiplegia. Although this is normally achieved using mechanical coupling (i.e., a physical connection between the hands), a virtual reality system relying on virtual coupling (i.e., through a shared virtual object) would be simpler to use and prevent slacking. However, it is not clear whether different coupling modes differently impact task performance and effort distribution between the hands. We explored how 18 healthy right-handed participants changed their motor behaviors in response to the uninstructed addition of mechanical coupling, and virtual coupling using a shared cursor mapped to the average hands' position. In a second experiment, we then studied the impact of connection stiffness on performance, perception, and effort imbalance. The results indicated that both coupling types can induce the hands to actively contribute to the task. However, the task asymmetry introduced by using a cursor mapped to either the left or right hand only modulated the hands' contribution when not mechanically coupled. The tracking performance was similar for all coupling types, independent of the connection stiffness, although the mechanical coupling was preferred and induced the hands to move with greater correlation. These findings suggest that virtual coupling can induce the hands to actively contribute to a task in healthy participants without hindering their performance. Further investigation on the coupling types' impact on the performance and hands' effort distribution in patients with hemiplegia could allow for the design of simpler training systems that promote the affected hand's use.NEW & NOTEWORTHY We showed that the uninstructed addition of a virtual and/or a mechanical coupling can induce both hands to actively contribute in a continuous redundant bimanual tracking task without impacting performance. In addition, we showed that the task asymmetry can only alter the effort distribution when the hands are not connected, independent of the connection stiffness. Our findings suggest that virtual coupling could be used in the development of simpler VR-based training devices.

Can Training Make Three Arms Better Than Two Heads for Trimanual Coordination?

Supernumerary effectors have been proposed to enable users to perform tasks alone that normally require assistance from a partner. While various supernumerary robotic limbs have been developed in the last decade, the capability of users to operate them effectively has not yet been proven. Here we tested whether users (i) can complete a task that requires simultaneous and fine control of three effectors, and (ii) can be trained to do so with similar or superior performance as through collaboration with a human partner. As in previous studies, initial augmented capability was less than that of working with a partner. However, one hour of dedicated solo trimanual training across three days significantly increased task performance, so that participants became able to perform trimanual control alone as well as or better than they could with a new partner. This shows the viability of augmentation systems for applications such as in robotic surgery or industrial assembly, which can be further validated on real tasks with physical systems.

Comparative Studies of Karyotypes in the Cervidae Family.

The family Cervidae is the second most diverse family in the infraorder Pecora and is characterized by a striking variability in the diploid chromosome numbers among species, ranging from 6 to 70. Chromosomal rearrangements in Cervidae have been studied in detail by chromosome painting. There are many comparative cytogenetic data for both subfamilies (Cervinae and Capreolinae) based on homologies with chromosomes of cattle and Chinese muntjac. Previously it was found that interchromosomal rearrangements are the major type of rearrangements occurring in the Cervidae family. Here, we build a detailed chromosome map of a female reindeer (Rangifer tarandus, 2n = 70, Capreolinae) and a female black muntjac (Muntiacus crinifrons, 2n = 8, Cervinae) with dromedary homologies to find out what other types of rearrangements may have underlined the variability of Cervidae karyotypes. To track chromosomal rearrangements and the distribution of nucleolus organizer regions not only during Cervidae but also Pecora evolution, we summarized new data and compared them with chromosomal maps of other already studied species. We discuss changes in the pecoran ancestral karyotype in the light of new painting data. We show that intrachromosomal rearrangements in autosomes of Cervidae are more frequent than previously thought: at least 13 inversions in evolutionary breakpoint regions were detected.

Exhaustion disorder: scoping review of research on a recently introduced stress-related diagnosis.

BACKGROUND: Symptoms related to chronic stress are prevalent and entail high societal costs, yet there is a lack of international consensus regarding diagnostics and treatment. A new stress-related diagnosis, exhaustion disorder, was introduced into the Swedish version of ICD-10 in 2005. Since then, use of the diagnosis has increased rapidly. AIMS: To create the first comprehensive synthesis of research on exhaustion disorder to report on the current state of knowledge. Preregistration: Open Science Framework (http://www.w3.org/1999/xlink">osf.io), doi 10.17605/OSF.IO/VFDKW. METHOD: A PRISMA-guided scoping review of all empirical studies of exhaustion disorder was conducted. Searches were run in the MEDLINE, PsycInfo and Web of Science databases. Data were systematically charted and thematically categorised based on primary area of investigation. RESULTS: Eighty-nine included studies were sorted into six themes relating to lived experience of exhaustion disorder (n = 9), symptom presentation and course (n = 13), cognitive functioning (n = 10), biological measures (n = 24), symptom measurement scales (n = 4) and treatment (n = 29). Several studies indicated that individuals with exhaustion disorder experience a range of psychiatric and somatic symptoms beyond fatigue, but robust findings within most thematic categories were scarce. The limited number of studies, lack of replication of findings and methodological limitations (e.g. small samples and scarcity of specified primary outcomes) preclude firm conclusions about the diagnostic construct. CONCLUSIONS: More research is needed to build a solid knowledge base for exhaustion disorder. International collaboration regarding the conceptualisation of chronic stress and fatigue is warranted to accelerate the growth of evidence.

Operational Definitions of Treatment Response and Remission in Obsessive-Compulsive Disorder Capture Meaningful Improvements in Everyday Life.

INTRODUCTION: The operational definitions of treatment response, partial response, and remission in obsessive-compulsive disorder (OCD) are widely used in clinical trials and regular practice. However, the clinimetric sensitivity of these definitions, that is, whether they identify patients that experience meaningful changes in their everyday life, remains unexplored. OBJECTIVE: The objective was to examine the clinimetric sensitivity of the operational definitions of treatment response, partial response, and remission in children and adults with OCD. METHODS: Pre- and post-treatment data from five clinical trials and three cohort studies of children and adults with OCD (n = 1,528; 55.3% children, 61.1% female) were pooled. We compared (1) responders, partial responders, and non-responders and (2) remitters and non-remitters on self-reported OCD symptoms, clinician-rated general functioning, and self-reported quality of life. Remission was also evaluated against post-treatment diagnostic interviews. RESULTS: Responders and remitters experienced large improvements across validators. Responders had greater improvements than partial responders and non-responders on self-reported OCD symptoms (Cohen's d 0.65-1.13), clinician-rated functioning (Cohen's d 0.53-1.03), and self-reported quality of life (Cohen's d 0.63-0.73). Few meaningful differences emerged between partial responders and non-responders. Remitters had better outcomes across most validators than non-remitters. Remission criteria corresponded well with absence of post-treatment diagnosis (sensitivity/specificity: 93%/83%). Using both the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the Clinical Global Impression Scale yielded more conservative results and more robust changes across validators, compared to only using the Y-BOCS. CONCLUSIONS: The current definitions of treatment response and remission capture meaningful improvements in the everyday life of individuals with OCD, whereas the concept of partial response has dubious clinimetric sensitivity.