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Abstract Introduction A dynamic molecular biomarker that can identify early efficacy of immune checkpoint inhibitor (ICI) therapy remains an unmet clinical need. Here we evaluate if a novel circulating tumor DNA (ctDNA) assay, xM, used for treatment response monitoring (TRM), that quantifies changes in ctDNA tumor fraction (TF), can predict outcome benefits in patients treated with ICI alone or in combination with chemotherapy in a real-world (RW) cohort. Methods This retrospective study consisted of patients with advanced cancer from the Tempus de-identified clinical genomic database who received longitudinal liquid-based next-generation sequencing. Eligible patients had a blood sample ≤ 40 days prior to the start of ICI initiation and an on-treatment blood sample 15–180 days post ICI initiation. TF was calculated via an ensemble algorithm that utilizes TF estimates derived from variants and copy number information. Patients with molecular response (MR) were defined as patients with a ≥ 50% decrease in TF between tests. In the subset of patients with rw-imaging data between 2 and 18 weeks of ICI initiation, the predictive value of MR in addition to rw-imaging was compared to a model of rw-imaging alone. Results The evaluable cohort (N = 86) was composed of 14 solid cancer types. Patients received either ICI monotherapy (38.4%, N = 33) or ICI in combination with chemotherapy (61.6%, N = 53). Patients with MR had significantly longer rw-overall survival (rwOS) (hazard ratio (HR) 0.4, P = 0.004) and rw-progression free survival (rwPFS) (HR 0.4, P = 0.005) than patients with molecular non-response (nMR). Similar results were seen in the ICI monotherapy subcohort; HR 0.2, P = 0.02 for rwOS and HR 0.2, P = 0.01 for rwPFS. In the subset of patients with matched rw-imaging data (N = 51), a model incorporating both MR and rw-imaging was superior in predicting rwOS than rw-imaging alone (P = 0.02). Conclusions xM used for TRM is a novel serial quantitative TF algorithm that can be used clinically to evaluate ICI therapy efficacy.

Abstract Automated online cognitive assessments are set to revolutionise clinical research and healthcare. However, their applicability for Parkinson’s Disease (PD) and REM Sleep Behavioural Disorder (RBD), a strong PD precursor, is underexplored. Here, we developed an online battery to measure early cognitive changes in PD and RBD. Evaluating 19 candidate tasks showed significant global accuracy deficits in PD (0.65 SD, p = 0.003) and RBD (0.45 SD, p = 0.027), driven by memory, language, attention and executive underperformance, and global reaction time deficits in PD (0.61 SD, p = 0.001). We identified a brief 20-min battery that had sensitivity to deficits across these cognitive domains while being robust to the device used. This battery was more sensitive to early-stage and prodromal deficits than the supervised neuropsychological scales. It also diverged from those scales, capturing additional cognitive factors sensitive to PD and RBD. This technology offers an economical and scalable method for assessing these populations that can complement standard supervised practices.

Abstract Liquid biopsy is a valuable precision oncology tool that is increasingly used as a non-invasive approach to identify biomarkers, detect resistance mutations, monitor disease burden, and identify early recurrence. The Tempus xF liquid biopsy assay is a 105-gene, hybrid-capture, next-generation sequencing (NGS) assay that detects single-nucleotide variants, insertions/deletions, copy number variants, and chromosomal rearrangements. Here, we present extensive validation studies of the xF assay using reference standards, cell lines, and patient samples that establish high sensitivity, specificity, and accuracy in variant detection. The Tempus xF assay is highly concordant with orthogonal methods, including ddPCR, tumor tissue-based NGS assays, and another commercial plasma-based NGS assay. Using matched samples, we developed a dynamic filtering method to account for germline mutations and clonal hematopoiesis, while significantly decreasing the number of false-positive variants reported. Additionally, we calculated accurate circulating tumor fraction estimates (ctFEs) using the Off-Target Tumor Estimation Routine (OTTER) algorithm for targeted-panel sequencing. In a cohort of 1,000 randomly selected cancer patients who underwent xF testing, we found that ctFEs correlated with disease burden and clinical outcomes. These results highlight the potential of serial testing to monitor treatment efficacy and disease course, providing strong support for incorporating liquid biopsy in the management of patients with advanced disease.

Speech impairment in Parkinson’s Disease (PD) has been extensively studied. Our understanding of speech in people who are at an increased risk of developing PD is, however, rather limited. It is known that isolated Rapid Eye Movement (REM) sleep Behavior Disorder (RBD) is associated with a high risk of developing PD. The aim of this study is to investigate smartphone speech testing to: (1) distinguish participants with RBD from controls and PD, and (2) predict a range of self- or researcher-administered clinical scores that quantify participants’ motor symptoms, cognition, daytime sleepiness, depression, and the overall state of health. The rationale of our analyses is to test an initial hypothesis that speech can be used to detect and quantify the symptoms associated with RBD and PD. We analyzed 4242 smartphone voice recordings collected in clinic and at home from 92 Controls, 112 RBD and 335 PD participants. We used acoustic signal analysis and machine learning, employing 337 features that quantify different properties of speech impairment. Using a leave-one-subject-out cross-validation scheme, we were able to distinguish RBD from controls (sensitivity 60.7%, specificity 69.6%) and RBD from PD participants (sensitivity 74.9%, specificity 73.2%), and predict clinical assessments with clinically useful accuracy. These promising findings warrant further investigation in using speech as a digital biomarker for PD and RBD to facilitate intervention in the early and prodromal stages of PD.

Abstract Objectives Rapid eye movement sleep behavior disorder (RBD) patients have a high risk of developing a Parkinsonian disorder, offering an opportunity for neuroprotective intervention. Predicting near‐term conversion, however, remains a challenge. Dopamine transporter imaging, while informative, is expensive and not widely available. Here, we investigate the utility of susceptibility‐weighted MRI (SWI) to detect abnormalities of the substantia nigra in RBD, and explore their association with striatal dopaminergic deficits. Methods SWI of the substantia nigra was performed in 46 RBD patients, 27 Parkinson’s patients, and 32 control subjects. Dorsal nigral hyperintensity (DNH) was scored by two blinded raters, and separately quantified using a semiautomated process. Forty‐two RBD patients were also imaged with 123I‐ioflupane single‐photon emission computed tomography (DaT SPECT/CT). Results Consensus visual DNH classification was possible in 87% of participants. 27.5% of RBD patients had lost DNH, compared with 7.7% of control subjects and 96% of Parkinson’s patients. RBD patients lacking DNH had significantly lower putamen dopaminergic SPECT/CT activity compared to RBD patients with DNH present (specific uptake ratios 1.89 vs. 2.33, P = 0.002). The mean quantified DNH signal intensity declined in a stepwise pattern, with RBD patients having lower intensity than controls (0.837 vs. 0.877, P = 0.01) but higher than PD patients (0.837 vs. 0.765, P

Abstract Objective We recently demonstrated that 998 features derived from a simple 7‐minute smartphone test could distinguish between controls, people with Parkinson's and people with idiopathic Rapid Eye Movement sleep behavior disorder, with mean sensitivity/specificity values of 84.6‐91.9%. Here, we investigate whether the same smartphone features can be used to predict future clinically relevant outcomes in early Parkinson's. Methods A total of 237 participants with Parkinson's (mean (SD) disease duration 3.5 (2.2) years) in the Oxford Discovery cohort performed smartphone tests in clinic and at home. Each test assessed voice, balance, gait, reaction time, dexterity, rest, and postural tremor. In addition, standard motor, cognitive and functional assessments and questionnaires were administered in clinic. Machine learning algorithms were trained to predict the onset of clinical outcomes provided at the next 18‐month follow‐up visit using baseline smartphone recordings alone. The accuracy of model predictions was assessed using 10‐fold and subject‐wise cross validation schemes. Results Baseline smartphone tests predicted the new onset of falls, freezing, postural instability, cognitive impairment, and functional impairment at 18 months. For all outcome predictions AUC values were greater than 0.90 for 10‐fold cross validation using all smartphone features. Using only the 30 most salient features, AUC values greater than 0.75 were obtained. Interpretation We demonstrate the ability to predict key future clinical outcomes using a simple smartphone test. This work has the potential to introduce individualized predictions to routine care, helping to target interventions to those most likely to benefit, with the aim of improving their outcome.

Introduction Parkinson’s disease (PD) is a common neurodegenerative disorder with substantial morbidity. No disease-modifying treatments currently exist. The glucagon like peptide-1 receptor agonist exenatide has been associated in single-centre studies with reduced motor deterioration over 1 year. The aim of this multicentre UK trial is to confirm whether these previous positive results are maintained in a larger number of participants over 2 years and if effects accumulate with prolonged drug exposure.Methods and analysis This is a phase 3, multicentre, double-blind, randomised, placebo-controlled trial of exenatide at a dose of 2 mg weekly in 200 participants with mild to moderate PD. Treatment duration is 96 weeks. Randomisation is 1:1, drug to placebo. Assessments are performed at baseline, week 12, 24, 36, 48, 60, 72, 84 and 96 weeks.The primary outcome is the comparison of Movement Disorders Society Unified Parkinson’s Disease Rating Scale part 3 motor subscore in the practically defined OFF medication state at 96 weeks between participants according to treatment allocation. Secondary outcomes will compare the change between groups among other motor, non-motor and cognitive scores. The primary outcome will be reported using descriptive statistics and comparisons between treatment groups using a mixed model, adjusting for baseline scores. Secondary outcomes will be summarised between treatment groups using summary statistics and appropriate statistical tests to assess for significant differences.Ethics and dissemination This trial has been approved by the South Central-Berkshire Research Ethics Committee and the Health Research Authority. Results will be disseminated in peer-reviewed journals, presented at scientific meetings and to patients in lay-summary format.Trial registration numbers NCT04232969, ISRCTN14552789.

Complications involving the central nervous system (CNS) occur in 9–14% of patients following allogeneic hematopoietic stem cell transplantation (HSCT), including stroke-like episodes, demyelination, encephalitis, and nonspecific neurological symptoms. Here we report a case of multiple sclerosis (MS) like relapsing remitting encephalomyelitis following allogeneic HSCT, which did not respond to disease modifying therapies (DMTs) and “domino” autologous HSCT. A 53-year-old male was treated with allogeneic HSCT for lymphoid blast transformation of chronic myeloid leukemia. Ten months later he presented with confusion, slurred speech, left sided facial weakness and ataxia. A magnetic resonance imaging brain scan showed multiple enhancing tumefactive lesions. Neuromyelitis optica (NMO) and myelin oligodendrocyte glycoprotein (MOG) antibodies were negative. After extensive investigations for infections, autoimmune disorders and recurrence of malignancy, he underwent brain biopsy, which showed a macrophage rich lesion with severe myelin loss but axonal preservation indicating a demyelinating pathology. Although his symptoms improved with corticosteroids, he relapsed five months later. In the absence of any systemic features suggesting graft versus host disease (GvHD), his presentation was thought to be compatible with MS. The illness followed an aggressive course that did not respond to glatiramer acetate and natalizumab. He was therefore treated with “domino” autologous HSCT, which also failed to induce long-term remission. Despite further treatment with ocrelizumab, he died of progressive disease. An autopsy limited to the examination of brain revealed multifocal destructive leukoencephalopathy with severe myelin and axonal loss. Immunohistochemistry showed macrophage located in the perivascular area, with no T or B lymphocytes. The appearance was unusual and not typical for chronic MS plaques. Reported cases of CNS demyelination following allogeneic HSCT are very limited in the literature, especially in relation to histopathological examination. Although the clinical disease course of our patient following allogeneic HSCT resembled an “MS-like” relapsing remitting encephalomyelitis, the autopsy examination did not show any evidence of active inflammation. The impact of DMTs and HSCT on the histological appearance of “MS-like” CNS pathologies is unknown. Therefore, reporting this and similar cases will improve our awareness and understanding of underlying disease mechanisms.

Abstract Background For (123I)FP-CIT imaging, a number of algorithms have shown high performance in distinguishing normal patient images from those with disease, but none have yet been tested as part of reporting workflows. This study aims to evaluate the impact on reporters’ performance of a computer-aided diagnosis (CADx) tool developed from established machine learning technology. Three experienced (123I)FP-CIT reporters (two radiologists and one clinical scientist) were asked to visually score 155 reconstructed clinical and research images on a 5-point diagnostic confidence scale (read 1). Once completed, the process was then repeated (read 2). Immediately after submitting each image score for a second time, the CADx system output was displayed to reporters alongside the image data. With this information available, the reporters submitted a score for the third time (read 3). Comparisons between reads 1 and 2 provided evidence of intra-operator reliability, and differences between reads 2 and 3 showed the impact of the CADx. Results The performance of all reporters demonstrated a degree of variability when analysing images through visual analysis alone. However, inclusion of CADx improved consistency between reporters, for both clinical and research data. The introduction of CADx increased the accuracy of the radiologists when reporting (unfamiliar) research images but had less impact on the clinical scientist and caused no significant change in accuracy for the clinical data. Conclusions The outcomes for this study indicate the value of CADx as a diagnostic aid in the clinic and encourage future development for more refined incorporation into clinical practice.

Abstract Introduction The relationship between posture and temporomandibular disease (TMD) is unclear. The aim of our study was to determine the influence of manual therapy (MT) on posture in TMD patients compared with healthy subjects. Material/method After consideration of inclusion and exclusion criteria, 30 subjects were included. These were divided into two groups: group A comprised 15 healthy subjects and group B 15 patients with present proven TMD disease. Rasterstereographic images were taken at different times. Group A subjects were scanned twice within half a year and group B before initiation as well as after the first MT and after completion of the prescribed MT. The different posture variables were calculated using DIERS Formetric software. Results To illustrate the differences between the two groups, 10 different postural variables were examined. Significant differences between the two groups were observed in pelvic tilt, surface rotation, and kyphotic apex. Pelvic tilt: mean = 7.581, p-value = 0.029; surface rotation: mean = 3.098, p = 0.049; and mean kyphotic apex = 11.538 and 11.946, respectively, with p-values of 0.037 and 0.029, respectively. Conclusion MT leads to a change in posture in TMD patients. This could influence the course of TMD treatment.

Abstract Background Coronary artery disease (CAD) confers increased risks of premature mortality, non-fatal morbidity, and significant impairment in functional status and health-related quality of life. Routine administration of electronic patient-reported outcome measures (PROMs) and its real time delivery to care providers is known to have the potential to inform routine cardiac care and to improve quality of care and patient outcomes. This study describes a user-centered development and evaluation of the Alberta Provincial Project for Outcomes Assessment (APPROACH) electronic Patient Reported Outcomes Measurement (e-PROM) system. This e-PROM system is an electronic system for the administration of PROMs to patients with CAD and the delivery of the summarized information to their care providers to facilitate patient-physician communication and shared decision-making. This electronic platform was designed to be accessible via web-based and hand-held devices. Heuristic and user acceptance evaluation were conducted with patients and attending care providers. Results The APPROACH e-PROM system was co-developed with patients and care providers, research investigators, informaticians and information technology experts. Five PROMs were selected for inclusion in the online platform after consultations with patient partners, care providers, and PROMs experts: the Seattle Angina Questionnaire, Patient Health Questionnaire, EuroQOL, and Medical Outcomes Study Social Support Survey, and Self-Care of Coronary Heart Disease Inventory. The heuristic evaluation was completed by four design experts who examined the usability of the prototype interfaces. User acceptance testing was completed with 13 patients and 10 cardiologists who evaluated prototype user interfaces of the e-PROM system. Conclusion Both patients and physicians found the APPROACH e-PROM system to be easy to use, understandable, and acceptable. The APPROACH e-PROM system provides a user-informed electronic platform designed to incorporate PROMs into the delivery of individualized cardiac care for persons with CAD.

Abstract Background People with a rare disease commonly experience long delays from the onset of symptoms to diagnosis. Rare diseases are challenging to diagnose because they are clinically heterogeneous, and many present with non-specific symptoms common to many diseases. We aimed to explore the experiences of people with myositis, primary immunodeficiency (PID), and sarcoidosis from symptom onset to diagnosis to identify factors that might impact receipt of a timely diagnosis. Methods This was a qualitative study using semi-structured interviews. Our approach was informed by Interpretive Phenomenological Analysis (IPA). We applied the lens of uncertainty management theory to tease out how patients experience, assess, manage and cope with puzzling and complex health-related issues while seeking a diagnosis in the cases of rare diseases. Results We conducted interviews with 26 people with a rare disease. Ten participants had been diagnosed with a form of myositis, 8 with a primary immunodeficiency, and 8 with sarcoidosis. Time to diagnosis ranged from 6 months to 12 years (myositis), immediate to over 20 years (PID), and 6 months to 15 years (sarcoidosis). We identified four themes that described the experiences of participants with a rare disease as they sought a diagnosis for their condition: (1) normalising and/or misattributing symptoms; (2) particularising by clinicians; (3) asserting patients’ self-knowledge; and (4) working together through the diagnosable moment. Conclusions Managing medical uncertainty in the time before diagnosis of a rare disease can be complicated by patients discounting their own symptoms and/or clinicians discounting the scale and impact of those symptoms. Persistence on the part of both clinician and patient is necessary to reach a diagnosis of a rare disease. Strategies such as recognising pattern failure and accommodating self-labelling are key to diagnosis.

Abstract The progression of Parkinson’s disease (PD) is associated with microstructural alterations in neural pathways, contributing to both motor and cognitive decline. However, conflicting findings have emerged due to the use of heterogeneous methods in small studies. Here we performed a large diffusion MRI study in PD, integrating data from 17 cohorts worldwide, to identify stage-specific profiles of white matter differences. Diffusion-weighted MRI data from 1654 participants diagnosed with PD (age: 20–89 years; 33% female) and 885 controls (age: 19–84 years; 47% female) were analyzed using the ENIGMA-DTI protocol to evaluate white matter microstructure. Skeletonized maps of fractional anisotropy (FA) and mean diffusivity (MD) were compared across Hoehn and Yahr (HY) disease groups and controls to reveal the profile of white matter alterations at different stages. We found an enhanced, more widespread pattern of microstructural alterations with each stage of PD, with eventually lower FA and higher MD in almost all regions of interest: Cohen’s d effect sizes reached d = −1.01 for FA differences in the fornix at PD HY Stage 4/5. The early PD signature in HY stage 1 included higher FA and lower MD across the entire white matter skeleton, in a direction opposite to that typical of other neurodegenerative diseases. FA and MD were associated with motor and non-motor clinical dysfunction. While overridden by degenerative changes in the later stages of PD, early PD is associated with paradoxically higher FA and lower MD in PD, consistent with early compensatory changes associated with the disorder.

Contexte : Les activités d’apprentissage par le service dans la communauté (ASC) sont intégrées au sein des facultés de médecine depuis plusieurs années. Toutefois, peu de données existent permettant de comprendre les retombées de ce type d’activités sur les personnes étudiantes et les milieux communautaires. Cette recherche visait à explorer les perceptions des retombées d’une activité de formation ASC offerte aux personnes étudiantes en médecine. Méthodes : Une étude qualitative descriptive interprétative a été menée. Elle incluait des entrevues semi-dirigées pré et post stage, menée auprès des personnes étudiantes ayant participé aux activités d’ASC (pré n=21, post n=7), de même que des groupes de discussion focalisée auprès d’intervenants ou responsables d’organismes communautaires (n=17). Résultats : Les expériences vécues au sein de milieux socioéconomiques et culturels pluriels ont contribué à améliorer la compréhension par les personnes étudiantes du concept de vulnérabilité sociale et du vécu des personnes vivant en contexte de vulnérabilité. L’ASC a également généré une meilleure perception de la compréhension de l’importance des organismes communautaires dans l’aide à ces personnes en situation de vulnérabilité. Conclusion : Dans le cadre de l’ASC, une meilleure compréhension des facteurs contribuant au développement de compétences touchant la pratique en contexte de vulnérabilité s’avère nécessaire pour permettre une expérience significative et souvent transformative chez les futurs médecins.

Abstract Objectives Caring for children in low- and middle-income countries (LMIC) can be challenging. This review article aims to explore role of telemedicine in supporting pediatric care in LMIC. Methodology A narrative review of existing English and Spanish literature was conducted to assess role of telemedicine to support pediatric care in LMIC. Results Beside medical education and direct pediatric care, telemedicine can provide sub-specialties consultations without extra burden on families. Additionally, telemedicine can help in lowering under-5 mortality by supporting neonatal care, infectious illnesses, and non-communicable diseases (NCDs). Telemedicine can be a gate for universal coverage for all children at a lower cost. For over a decade, it has been implemented successfully and sustained in a few LMIC. However, challenges in implementing telemedicine are enormous. Still, opportunities arise by using simpler technology, low-width band internet, smartphones, instant messaging applications and solar energy. COVID-19 pandemic facilitated acceptance and applicability of telemedicine worldwide including LMIC. Nevertheless, governments must regulate telemedicine by issuing policies and ensuring employment of local experts when possible to meet local resources and cultural competency. Conclusion Telemedicine has proven successful in improving pediatrics care. Many LMIC should take advantage of this innovation to promote equity and access to high quality pediatric care.

Introduction/Objectives: Exposure to adverse social determinants of health (SDoH) in childhood is associated with poorer long-term health outcomes. Within structurally marginalized populations, there are disproportionately high rates of developmentally vulnerable children. The RICHER (Responsive, Intersectoral, Child and Community Health, Education and Research) social pediatric model was designed to increase access to care in marginalized neighborhoods. The purpose of this study was to describe the children and youth engaged with the RICHER model of service and characterize the needs of the population. Methods: A retrospective chart review was conducted on children and youth who accessed primary care services through the program between January 1, 2018 and April 30, 2021. Basic descriptive data analysis was done using Stata v15.1. Results: A total of 210 charts were reviewed. The mean age in years at initial assessment was 6.32. Patients most commonly identified their race/ethnicity as Indigenous (33%) and 15% were recent newcomers to Canada. Evidence of at least 1 adverse SDoH was noted in 41% of charts; the most common included material poverty (34%), food insecurity (11%), and child welfare involvement (20%). The median number of diagnoses per patient was 4. The most frequently documented diagnoses were neurodevelopmental disorders (50%) including developmental delay (39%), ADHD (32%), and learning disability (26%). The program referred 72% of patients to general pediatricians and/or other subspecialists; 34% were referred for tertiary neuropsychological assessments and 35% for mental health services. Conclusions: Our data suggests that this low-barrier, place-based primary care RICHER model was able to reach a medically, developmentally, and socially complex population living in disenfranchised urban neighborhoods. Half of the patients identified in our review had neurodevelopmental concerns and a third had mental health concerns, in contrast to an estimated 17% prevalence for mental health, behavioral, or developmental disorders in North American general pediatric aged populations. This highlights the impact adverse SDoH can have on child health and the importance of working with community partners to identify developmentally vulnerable children and support place-based programs in connecting with children who may be missed, overlooked, or disadvantaged through traditional models of care.

IntroductionThe global health burden of chronic kidney disease (CKD) results from both the disease itself and the numerous health problems associated with it. The aim of this study was to estimate the prevalence of previously undetected CKD in middle-aged patients with risk factors for CKD. Identified patients were included in the Styrian nephrology awareness program “kidney.care 2.0” and data on their demographics, risk factors and kidney function were described.MethodsCross-sectional analysis of baseline data derived from the “kidney.care 2.0” study of 40–65 year old patients with at least one risk factor for CKD (hypertension, diabetes, cardiovascular disease, obesity or family history of end-stage kidney disease). Participants were considered to have previously undetected CKD if their estimated glomular filtration rate (eGFR) was less than 60 ml/min/1.73 m2 and/or albumin creatinine ratio (ACR) ≥ 30 mg/g. We calculated the prevalence of previously undetected CKD and performed multivariate analyses.ResultsA total of 749 participants were included in this analysis. The prevalence of previously undetected CKD in an at-risk population was estimated at 20.1% (95%CI: 17.1–23.6). Multivariable analysis showed age (OR 1.06, 95%CI: 1.02–1.09), diabetes mellitus (OR 1.65, 95%CI: 1.12–2.30) and obesity (OR: 1.55, 95%CI: 1.04–2.30) to be independent predictors of CKD. The majority of patients with previously undetected CKD had category A2-A3 albuminuria (121 out of 150). Most patients with previously undetected eGFR < 60 ml/min/1.73 m2 were in stage G3 (36 out of 39 patients).DiscussionPragmatic, targeted, risk-based screening for CKD in primary care successfully identified a significant number of middle-aged patients with previously undetected CKD and addressed the problem of these patients being overlooked for future optimized care. The intervention may slow progression to kidney failure and prevent related cardiovascular events.

Background: There are several established structured diagnostic interviews that cover common mental disorders seen in general psychiatry clinics. The administration of more focused diagnostic interviews may be useful in specialty clinics, such as OCD clinics. A semi-structured clinician-administered interview for obsessive-compulsive spectrum disorders (SCID-OCSD) was developed and adapted for DSM-5/ICD-11 obsessive-compulsive and related disorders as well as other putative obsessive-compulsive spectrum conditions. Objective: To introduce a semi-structured diagnostic interview for in-depth assessment of obsessive-compulsive spectrum disorders (OCSDs), and to report on its implementation in adults with primary OCD attending an OCD-specialized unit. Methods: Patients with primary OCD were interviewed using the SCID-OCSD. The SCID-OCSD assesses disorders drawn from several diagnostic categories that share some core features of obsessive-compulsive phenomenology and that are often comorbid in OCD (e.g., obsessive-compulsive related disorders, impulse-control disorders, and a spectrum of compulsive-impulsive conditions such as tics, eating disorders, non-suicidal self-injury, and behavioral addictions. Participants had to be at least moderately symptomatic on the Yale-Brown Obsessive-Compulsive Severity scale (YBOCS, i.e., a total score ≥ 14) to be included in the current study. Results: One hundred and one adult patients with current OCD (n = 101, 37 men and 64 women), took part in the study. Forty-two participants (n = 42) had OCD and one or more current or past comorbid OCSDs, with excoriation (skin-picking) disorder (n = 16) and body dysmorphic disorder (n = 14) being the most common. Nine (n = 9) participants reported a history of non-suicidal self-injury, and 6 participants reported a history of comorbid tics. Conclusions: In OCD clinics, the SCID-OCSD may help diagnose the full range of putative OCSDs, and so facilitate treatment planning and research on these conditions.

ABSTRACT Microorganisms interact with plant roots through colonization of the root surface, i.e., the rhizoplane or the surrounding soil, i.e., the rhizosphere. Beneficial rhizosphere bacteria such as Pseudomonas spp. can promote plant growth and protect against pathogens by producing a range of bioactive compounds, including specialized metabolites like cyclic lipopeptides (CLPs) known for their biosurfactant and antimicrobial activities. However, the role of CLPs in natural soil systems during bacteria-plant interactions is underexplored. Here, Pseudomonas fluorescens SBW25, producing the CLP viscosin, was used to study the impact of viscosin on bacterial root colonization and microbiome assembly in two cultivars of winter wheat (Heerup and Sheriff). We inoculated germinated wheat seeds with SBW25 wild type or a viscosin-deficient mutant and grew the plants in agricultural soil. After 2 weeks, enhanced root colonization of SBW25 wild type compared to the viscosin-deficient mutant was observed, while no differences were observed between wheat cultivars. In contrast, the impact on root-associated microbial community structure was plant-genotype-specific, and SBW25 wild type specifically reduced the relative abundance of an unclassified oomycete and Phytophthora in Sheriff and Heerup, respectively. This study provides new insights into the natural role of viscosin and specifically highlights the importance of viscosin in wheat root colonization under natural soil conditions and in shaping the root microbial communities associated with different wheat cultivars. Furthermore, it pinpoints the significance of microbial microdiversity, plant genotype, and microbe-microbe interactions when studying colonization of plant roots.IMPORTANCEUnderstanding parameters governing microbiome assembly on plant roots is critical for successfully exploiting beneficial plant-microbe interactions for improved plant growth under low-input conditions. While it is well-known from in vitro studies that specialized metabolites are important for plant-microbe interactions, e.g., root colonization, studies on the ecological role under natural soil conditions are limited. This might explain the often-low translational power from laboratory testing to field performance of microbial inoculants. Here, we showed that viscosin synthesis potential results in a differential impact on the microbiome assembly dependent on wheat cultivar, unlinked to colonization potential. Overall, our study provides novel insights into factors governing microbial assembly on plant roots, and how this has a derived but differential effect on the bacterial and protist communities.