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Background: Longitudinal cohort studies are pivotal to understand how socioeconomic, environmental, biological, and lifestyle factors influence health and disease. The added value of cohort studies increases as they accumulate life course data and expand across generations. Ensuring that participants stay motivated to contribute over decades of follow-up is, however, challenging. Participant engagement and involvement (PEI) aims to secure the long-term commitment of participants and promote researcher-participant interaction. This study explored PEI practices in a selection of pregnancy and birth, twin, and family-based population cohort studies. Methods: Purposive sampling was used to identify cohorts in Europe, Australia and New Zealand. Fourteen semi-structured digital interviews were conducted with cohort study representatives to explore strategies for participant recruitment, informed consent, communication of general and individual information to participants, data collection, and participant involvement. Experiences, resources allocated to PEI, and reflections on future PEI, were discussed. The interview data were analyzed using a content analysis approach and summary results were reviewed and discussed by the representatives. Results: The cohort studies used various strategies to recruit participants including support from health professionals and organizations combined with information on the studies' web sites and social media. New approaches such as intra-cohort recruitment, were being investigated. Most cohorts transitioned from paper-based to digital solutions to collect the participants' consent and data. While digital solutions increased efficiency, they also brought new challenges. The studies experimented with the use of participant advisory panels and focus groups to involve participants in making decisions, although their success varied across age and socio-economic background. Most representatives reported PEI resources to be limited and called for more human, technical, educational and financial resources to maximize the positive effects of PEI. Conclusions: This study of PEI among well-established cohort studies underscores the importance of PEI for project sustainability and highlights key factors to consider in developing PEI. Our analysis shows that knowledge gaps exist regarding which approaches have highest impact on retention rates and are best suited for different participant groups. Research is needed to support the development of best practices for PEI as well as knowledge exchange between cohorts through network building. [ABSTRACT FROM AUTHOR]

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Background: The allo-octoploid Fragaria x ananassa follows disomic inheritance, yet the high sequence similarity among its subgenomes can lead to misalignment of short sequencing reads (150 bp). This misalignment results in an increased number of erroneous variants during variant calling. To accurately associate traits with the appropriate subgenome, it is essential to filter out these erroneous variants. By classifying variants into correct (type 1) and erroneous types (homoeologous variants—type 2, and multi-locus variants—type 3), we can improve the reliability of downstream analyses. Results: Our analysis reveals that while erroneous variant types often display skewed average allele balances (AAB) for heterozygous calls, this measure alone is insufficient. To mitigate the erroneous variants further, we employed a Linkage Disequilibrium (LD) based filtering method that correlates highly (99%) with an approach that utilizes a genetic map from a biparental population. This combined filtering strategy—using both LD-based and average allele balance methods—resulted in the lowest switch error rate (0.037). Notably, our best filtering approach decreased phasing switch error rates by 44% and preserved 72% of the original dataset. Conclusions: The results indicate that identifying erroneous variants due to subgenome similarity can be effectively achieved without extensive genotyping of mapping populations. By implementing the LD-based filtering method, the phasing accuracy improved which improves the tracability of important alleles in the germplasm, paving the way for better understanding of trait associations in F. x ananassa. [ABSTRACT FROM AUTHOR]

Path integration, the process of updating one's position using successive self-motion signals, has previously been studied with visual distance reproduction tasks in which optic flow patterns provide information about traveled distance. These studies have reported that reproduced distances show two types of systematic biases: central tendency and serial dependence. In the present study, we investigated whether these biases are also present in vestibular path integration. Participants were seated on a linear motion platform and performed a distance reproduction task in total darkness. The platform first passively moved the participant a predefined stimulus distance, which they then actively reproduced by steering the platform back the same distance. Stimulus distances were sampled from short- and long-distance probability distributions and presented either in a randomized order or in separate blocks to study the effect of presentation context. Similar to the effects observed in visual path integration, we found that reproduced distances showed an overall positive central tendency effect as well as a positive, attractive serial dependence effect. Furthermore, reproduction behavior was affected by presentation context. These results were mostly consistent with predictions of a Bayesian Kalman filter model, originally proposed for visual path integration. NEW & NOTEWORTHY: Distance reproduction tasks based on visual information about the traveled distance have shown that reproductions are biased by central tendency and serial dependence effects. Here, we show that distance reproductions based on vestibular signals show similar biases and that the reproductions are affected by the presentation order of the stimulus distances. [ABSTRACT FROM AUTHOR]

Objective (s): Circulating angiogenic factors are used for prediction of placenta-related complications, but their associations with first-trimester placental development is unknown. This study investigates associations between maternal angiogenic factors and utero-placental vascular volume (uPVV) and utero-placental vascular skeleton (uPVS) as novel imaging markers of volumetric and morphologic (branching) development of the first-trimester utero-placental vasculature. Methods: In 185 ongoing pregnancies from the VIRTUAL Placenta study, a subcohort of the ongoing prospective Rotterdam Periconception cohort, three-dimensional power Doppler ultrasounds of the placenta were obtained at 7–9–11 weeks gestational age (GA). The uPVV was measured as a parameter of volumetric development and reported the vascular quantity in cm3. The uPVS was generated as a parameter of morphologic (branching) development and reported the number of end-, bifurcation- crossing- or vessel points and total vascular length. At 11 weeks GA, maternal serum biomarkers suggested to reflect placental (vascular) development were assessed: placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng). sFlt-1/PlGF and sEng/PlGF ratios were calculated. Multivariable linear regression with adjustments was used to estimate associations between serum biomarkers and uPVV and uPVS trajectories. Results: Serum PlGF was positively associated with uPVV and uPVS development (uPVV: β = 0.39, 95% CI = 0.15;0.64; bifurcation points: β = 4.64, 95% CI = 0.04;9.25; crossing points: β = 4.01, 95% CI = 0.65;7.37; total vascular length: β = 13.33, 95% CI = 3.09;23.58, all p-values < 0.05). sEng/PlGF ratio was negatively associated with uPVV and uPVS development. We observed no associations between sFlt-1, sEng or sFlt-1/PlGF ratio and uPVV and uPVS development. Conclusion(s): Higher first-trimester maternal serum PlGF concentration is associated with increased first-trimester utero-placental vascular development as reflected by uPVV and uPVS. Clinical trial registration number Dutch Trial Register NTR6854. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Is early embryonic size and growth in the first trimester of pregnancy associated with adverse birth outcomes? SUMMARY ANSWER Larger embryonic crown–rump length (CRL) and embryonic volume (EV) are associated with lower odds of adverse birth outcomes, especially small for gestational age (SGA). WHAT IS ALREADY KNOWN Preterm birth, SGA, and congenital anomalies are the most prevalent adverse birth outcomes with lifelong health consequences as well as high medical and societal costs. In the late first and second trimesters of pregnancy, fetuses at risk for adverse birth outcomes can be identified using 2-dimensional ultrasonography (US). STUDY DESIGN, SIZE, DURATION Between 2009 and 2018, singleton pregnancies were enrolled in this ongoing prospective Rotterdam Periconception Cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS This study included 918 pregnant women from a tertiary hospital in the Netherlands. Pregnancy dating was based on either a regular menstrual cycle (for natural pregnancies) or a conception date (for ART pregnancies). CRL and EV were measured using Virtual Reality software on 3-dimensional (3D) ultrasound scans, repeatedly performed around 7, 9, and 11 weeks of gestation. The main outcome measure was adverse birth outcome, defined as the composite of SGA (birth weight <10th percentile), preterm birth (<37th week of gestation), congenital anomalies (Eurocat criteria), stillbirth (>16th week of pregnancy), or early neonatal mortality (≤7 days of life). Reference curves for CRL and EV were constructed. Cross-sectional (CRL/EV <20th percentile at 7, 9, and 11 weeks of gestation) and longitudinal (CRL/EV growth trajectories between 6th and 13th weeks) regression analyses were performed, with adjustments for the participants' educational level, smoking, parity, age, BMI, geographical background, mode of conception, and fetal sex. MAIN RESULTS AND THE ROLE OF CHANCE Of the 918 pregnant women included, the median age was 32.3 years, and 404 (44%) pregnancies had been conceived via ART. In 199 (22%) pregnancies, there was an adverse birth outcome. Regression analyses showed that at 7 weeks of gestation onwards, embryos with a CRL <20th percentile had an ∼2-fold increased odds of adverse birth outcome (adjusted odds ratio (aOR) 2.03, 95% CI 1.21—3.39, P  = 0.007). Similar associations were found for EV <20th percentile but were not statistically significant. These findings were mainly driven by the strong association between embryonic size and SGA (e.g. 7-week CRL: aOR 2.18 (1.16–4.09), P  = 0.02; 9-week EV: aOR 2.09 (1.10—3.97, P  = 0.02). Longitudinal growth trajectories of CRL, but not of EV, were associated with adverse birth outcomes. Both CRL and EV growth trajectories were associated with SGA. LIMITATIONS, REASONS FOR CAUTION The tertiary hospital population and the availability of sophisticated 3D-ultrasound techniques limit the generalizability of this study to general populations and settings. WIDER IMPLICATIONS OF THE FINDINGS Already very early in the first trimester of pregnancy, embryos with increased risks of an adverse birth outcome can be identified by using 3D-US and Virtual Reality. This expands the window of opportunity to enable the development of future interventions to potentially improve pregnancy outcomes and offspring health during their life-course. STUDY FUNDING/COMPETING INTEREST(S) This work was funded by the Department of Obstetrics and Gynecology, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER NL4115. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Is the degree of maternal vulnerability positively associated with stress biomarkers (stress hormones, C-reactive protein, tryptophan metabolites, and one-carbon metabolites), and does long-term exposure to stress hormones reduce first-trimester growth? SUMMARY ANSWER The maternal vulnerability risk score is positively associated with concentrations of hair cortisol and cortisone and negatively with tryptophan, while higher hair cortisol concentrations are associated with reduced first-trimester growth without mediation of tryptophan. WHAT IS KNOWN ALREADY A high degree of maternal vulnerability during the periconception period is associated with impaired first-trimester growth and pregnancy complications, with consequences for long-term health of the child and future life course. However, due to the challenges of early identification of vulnerable women, the uptake of periconception care is low in this target group. STUDY DESIGN, SIZE, DURATION Between June 2022 and June 2023, this study was conducted in a sub-cohort of 160 pregnant women participating in the Rotterdam Periconceptional Cohort (Predict Study), an ongoing prospective tertiary hospital-based cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS One hundred and thirty-two women with ongoing pregnancies and available stress biomarker data were included in the analysis. Data on periconceptional social, lifestyle, and medical risk factors were collected via self-administered questionnaires, and these factors were used for the development of a composite maternal vulnerability risk score. Stress biomarkers, including stress hormones (hair cortisol and cortisone) and inflammatory and oxidative stress biomarkers (C-reactive protein, total homocysteine, and tryptophan metabolites) were determined in the first trimester of pregnancy. First-trimester growth was assessed by crown–rump length (CRL) and embryonic volume (EV) measurements at 7, 9, and 11 weeks gestation by making use of an artificial intelligence algorithm and virtual reality techniques using 3D ultrasound data sets. The associations between the maternal vulnerability risk score and stress biomarkers were identified using linear regression models, and between stress hormones and CRL- and EV-trajectories using mixed models. A mediation analysis was performed to assess the contribution of tryptophan. All associations were adjusted for potential confounders, which were identified using a data-driven approach. Several sensitivity analyses were performed to check the robustness of the findings. MAIN RESULTS AND THE ROLE OF CHANCE The maternal vulnerability risk score was positively associated with concentrations of hair cortisol and cortisone (pg/mg) (β = 0.366, 95% CI = 0.010–0.722; β = 0.897, 95% CI = 0.102–1.691, respectively), and negatively with tryptophan concentrations (µmol/L) (β = –1.637, 95% CI = –2.693 to –0.582). No associations revealed for C-reactive protein and total homocysteine. Higher hair cortisol concentrations were associated with reduced EV-trajectories (3√EV: β = –0.010, 95% CI = –0.017 to –0.002), while no associations were found with CRL-trajectories. Mediation by tryptophan was not shown. LIMITATIONS, REASONS FOR CAUTION Residual confounding cannot be ruled out, and the external validity may be limited due to the study's single-center observational design in a tertiary hospital. WIDER IMPLICATIONS OF THE FINDINGS There is mounting evidence that a high degree of maternal vulnerability negatively affects maternal and perinatal health, and that of the future life course. The results of our study emphasize the need to identify highly vulnerable women as early as possible, at least before conception. Our findings suggest that the chronic stress response and alterations of the maternal tryptophan metabolism are involved in maternal vulnerability, affecting first-trimester growth, with potential impact on the long-term health of the offspring. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the Departments of Obstetrics and Gynecology and Clinical Chemistry of the Erasmus MC, University Medical Center, Rotterdam, the Netherlands, and the Junior Award granted by the De Snoo—van 't Hoogerhuijs Foundation in March 2022. There are no conflicts of interest. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Recent research on thick terms like "rude" and "friendly" has revealed a polarity effect, according to which the evaluative content of positive thick terms like "friendly" and "courageous" can be more easily canceled than the evaluative content of negative terms like "rude" and "selfish". In this paper, we study the polarity effect in greater detail. We first demonstrate that the polarity effect is insensitive to manipulations of embeddings (Study 1). Second, we show that the effect occurs not only for thick terms but also for thin terms such as "good" or "bad" (Study 2). We conclude that the polarity effect indicates a pervasive asymmetry between positive and negative evaluative terms. [ABSTRACT FROM AUTHOR]

Purpose: Selection for postgraduate medical training is high-stakes and complex. The learning value of assessments for selection has, thus far, been underexplored, limiting their uptake as potentially meaningful learning experiences. The aim of this study was to explore the learning value residency applicants derive from an intelligence, personality, motivation and competency selection assessment and what factors influence the experienced learning value. Methods: In Autumn 2020 and Spring 2021, we conducted individual semi-structured interviews with sixteen applicants for pediatric residency training. Selection outcomes were unknown at the time of the interview. Interviews were transcribed verbatim and thematically analyzed. Results: Participants reported that the assessment was valuable in fostering self-reflection and self-awareness, embracing self-acceptance, pursuing development goals, assessing professional fit, and harnessing motivational drivers in work. The experienced learning value was influenced by applicants' ability to interpret its results, their focus on the high-stakes selection process and concerns regarding the acceptability and credibility of the selection tool. Conclusions: While the selection assessment showed learning potential, its learning value was impeded by a preoccupation with the high-stakes nature of the selection procedure. Intentional integration of the selection assessment in the learning curriculum may play a pivotal role in realizing its learning potential. [ABSTRACT FROM AUTHOR]

SUMMARY: Cyst nematodes establish permanent feeding structures called syncytia inside the host root vasculature, disrupting the flow of water and minerals. In response, plants form WOX11‐mediated adventitious lateral roots at nematode infection sites. WOX11 adventitious lateral rooting modulates tolerance to nematode infections; however, whether this also benefits nematode parasitism remains unknown. Here, we report on bioassays using a 35S::WOX11‐SRDX transcriptional repressor mutant to investigate whether WOX11 adventitious lateral rooting promotes syncytium development and thereby female growth and fecundity. Moreover, we chemically inhibited cellulose biosynthesis to verify if WOX11 directly modulates cell wall plasticity in syncytia. Finally, we performed histochemical analyses to test if WOX11 mediates syncytial cell wall plasticity via reactive oxygen species (ROS). Repression of WOX11‐mediated transcription specifically enhanced the radial expansion of syncytial elements, increasing both syncytium size and female offspring. The enhanced syncytial hypertrophy observed in the 35S::WOX11‐SRDX mutant could be phenocopied by chemical inhibition of cellulose biosynthesis and was associated with elevated levels of ROS at nematode infection sites. We, therefore, conclude that WOX11 restricts radial expansion of nematode‐feeding structures and female growth and fecundity, likely by modulating ROS‐mediated cell wall plasticity mechanisms. Remarkably, this novel role of WOX11 in plant cell size control is distinct from WOX11 adventitious lateral rooting underlying disease tolerance. Significance Statement: In this study, we uncover a novel role for WOX11 in Arabidopsis, which may help plants cope with infections by endoparasitic cyst nematodes in the field. By controlling plant cell size, WOX11 significantly limits the expansion of nematode feeding sites, ultimately reducing nematode offspring size. [ABSTRACT FROM AUTHOR]

Given the rise of digital technology and its assumed impact on psychological well-being, this scoping review systematically examines the literature on Fear of Missing Out (FoMO), which is assumed to play a pivotal role in this dynamic. Although adverse effects of FoMO are commonly assumed, there is still no consensus on the nature of the phenomenon or its relations with psychological well-being and digital technology use, making a scoping review essential. To address this need, we comprehensively assess the conceptualizations of the construct of FoMO and its roles in relation to well-being and digital technology use. We conducted a literature search in PubMed, Ebsco/APA PsycINFO, and Web of Science (period 2013 to July 7, 2023), screening 4121 articles at the title and abstract level and assessing 342 full-text articles for eligibility, ultimately including 106 articles. The review revealed a fragmented FoMO literature, emphasizing the need for conceptual clarity to address critical gaps and inconsistencies in existing research. Consensus exists on FoMO's essence—an unpleasant feeling arising from missed social experiences driven by activity comparison. However, debates include FoMO's associated affective states and conceptual boundaries, as well as the need to disentangle FoMO as a trait or state. The review also underscored FoMO's multifaceted roles in well-being and digital technology use, highlighting the need for causal research, theoretical guidance, and unified terminology to advance understanding in the FoMO literature. [ABSTRACT FROM AUTHOR]

INTRODUCTION Due to a continuing international trend of decentralization of public health policies, local governments are given an increasingly important role in tobacco control. The process of developing local-level tobacco control policies is an underexplored topic. This study uses grant applications as a data source to gain insight into the planning, development and proposed implementation of local tobacco control policies by regional public health departments in the Netherlands. METHODS Grant applications of 24 regional public health departments were analyzed using the second stage of the rational policy cycle, a four-stages policy model about the decisions made by local policy makers during the policy process. We coded the applications with open and axial coding. RESULTS Public health departments formulated four main goals for tobacco control: adding tobacco control policies to existing local policy documents, creating smokefree (child) environments, developing and improving access to smoking cessation care, and participating in media campaigns. Public health departments often specify tobacco control aims and involve partners in reaching these aims. However, the grant applications lacked information about implementing these tobacco control policies. CONCLUSIONS The information on implementation strategies and process evaluation, as well as the (evidence-based) legitimation for the policy choices, needs improvement. Under the current conditions, which include the brief explanation the departments received, an unclear mandate, insufficient funding, and local restricting factors such as time and knowledge, significant contributions to tobacco control policy cannot be expected from local governments. [ABSTRACT FROM AUTHOR]

Degenerative joint disease osteoarthritis (OA) is characterized by the degeneration of cartilage, synovial inflammation and low-grade systemic inflammation in association with microbial dysbiosis and intestinal barrier defects. Butyrate is known for its anti-inflammatory and barrier protective effects and might benefit OA patients. In a double-blind placebo-controlled randomized trial, the effects of four to five weeks of oral treatment with sustained-release (SR) butyrate tablets (600 mg/day) on systemic inflammation and immune function were studied in hand OA patients. Serum markers for systemic inflammation and lipopolysaccharide (LPS) leakage were measured and ex vivo stimulation of whole blood or peripheral blood mononuclear cells (PBMCs) was performed at baseline and after treatment. Butyrate treatment did not affect the serum markers nor the cytokine release of ex vivo LPS-stimulated whole blood or PBMCs nor the phenotype of restimulated monocytes. By contrast, butyrate treatment reduced the percentage of activated T helper (Th) cells and the Th17/Treg ratio in αCD3/CD28-activated PBMCs, though cytokine release upon stimulation remained unaffected. Nevertheless, the percentage of CD4+IL9+ cells was reduced by butyrate as compared to the placebo. In both groups, the frequency of Th1, Treg, Th17, activated Th17, CD4+IFNγ+ and CD4+TNFα+ cells was reduced. This study shows a proof of principle of some immunomodulatory effects using a SR butyrate treatment in hand OA patients. The inflammatory phenotype of Th cells was reduced, as indicated by a reduced percentage of Th9 cells, activated Th cells and improved Th17/Treg balance in ex vivo αCD3/CD28-activated PBMCs. Future studies are warranted to further optimize the butyrate dose regime to ameliorate inflammation in OA patients. [ABSTRACT FROM AUTHOR]

Purpose: To ensure comparable PET/CT image quality between or within centres, clinical inter-system performance comparisons following European Association of Nuclear Medicine Research Ltd. (EARL) guidelines is required. In this work the performance of the long axial field-of-view Biograph Vision Quadra is compared to its predecessor, the short axial field-of-view Biograph Vision. Procedures: To this aim, patients with suspected tumour lesions received a single weight-based (3 MBq/kg) 2-deoxy-2-[18F]fluoro-D-glucose injection and underwent routine clinical (∼ 15 min) scans on the Vision and 3-min scans on the Quadra in listmode in balanced order. Image quality (IQ), image noise (IN), and tumour demarcation (TD) were assessed visually by four nuclear medicine physicians using a 5-point Likert scale and semiquantitative analysis was performed using standardised uptake values (SUVs). Inter-reader agreement was tested using Wilcoxon's signed rank test and the SUVs were statistically compared using a paired t-test. Results: Twenty patients (mean age, 60 years ± 8.8 [standard deviation], 16 male) were enrolled. Inter-reader agreement ranged from good to very good for IQ and IN (0.62 ≤ W ≤ 0.81), and fair for TD (0.29 ≤ W ≤ 0.39). Furthermore, a significant difference was found for TD (p = 0.015) between the systems, showing improved TD for the Quadra. Conclusion: This study demonstrates that the Quadra can be used in routine clinical practice with multiple PET/CT systems or in multicentre studies. This system provides comparable diagnostic image quality and semiquantitative accuracy, improved TD, and has the advantage of shorter scan durations. [ABSTRACT FROM AUTHOR]

Plants have an amazing ability to adapt to their environment, and this extends beyond biochemical responses and includes developmental changes that help them better exploit resources and survive. The plasticity observed in individual plant morphology is associated with robust developmental pathways that are influenced by environmental factors. However, there is still much to learn about the mechanisms behind the formation of the root system. In Arabidopsis thaliana, the root system displays a hierarchical structure with primary and secondary roots. The process of lateral root (LR) organogenesis involves multiple steps, including LR pre-patterning, LR initiation, LR outgrowth, and LR emergence. The study of root developmental plasticity in Arabidopsis has led to significant progress in understanding the mechanisms governing lateral root formation. The importance of root system architecture lies in its ability to shape the distribution of roots in the soil, which affects the plant's ability to acquire nutrients and water. In Arabidopsis, lateral roots originate from pericycle cells adjacent to the xylem poles known as the xylem-pole-pericycle (XPP). The positioning of LRs along the primary root is underpinned by a repetitive pre-patterning mechanism that establishes primed sites for future lateral root formation. In a subset of primed cells, the memory of a transient priming stimulus leads to the formation of stable pre-branch sites and the establishment of founder cell identity. These founder cells undergo a series of highly organized periclinal and anticlinal cell divisions and expansion to form lateral root primordia. Subsequently, LRP emerges through three overlying cell layers of the primary root, giving rise to fully developed LRs. In addition to LRs Arabidopsis can also develop adventitious lateral roots from the primary root in response to specific stress signals such as wounding or environmental cues. Overall, this review creates an overview of the mechanisms governing root lateral root formation which can be a stepping stone to improved crop yields and a better understanding of plant adaptation to changing environments. [ABSTRACT FROM AUTHOR]

Ad creativity, based on the originality, meaningfulness, and craftsmanship of a brand message, is widely studied as an important mechanism of advertising success. These studies are based on practitioners' and consumers' creativity assessments. The purpose of this study is to evaluate the creativity assessments of these two groups against empirical standards in terms of intercoder reliability, stability, criterion validity, and predictive validity. To address this aim, sixty Instagram brand messages from the top-100 most interactive Instagram brand accounts were assessed by practitioners, consumers, and trained advertising researchers (for examining criterion validity). The results showed that practitioners and consumers can produce stable creativity assessments provided that the number of coders is large enough. Moreover, the results showed that assessments of both groups differed in terms of criterion validity. Examining the predictive validity showed that both groups yielded different outcome measures. These results (1) confirm that the creativity assessments of practitioners and consumers differ and (2) show that the quality of these assessments are contingent on the group of assessors (practitioners or consumers), sample size, and the assessed creativity dimensions. These findings have important implications for the design, evaluation, and comparability of creativity studies. [ABSTRACT FROM AUTHOR]

Context Several challenges still exist to adopt the anti-müllerian hormone (AMH) as a marker of polycystic ovary morphology, as included in the recently updated international guideline. Although different evaluations of age- and assay-specific reference ranges have been published in the past few years, these studies have mainly been conducted in normo-ovulatory or infertile women. Objective To develop an age-specific percentile distribution of AMH in patients with polycystic ovary syndrome (PCOS) measured by 3 different assays. Design Retrospective cross-sectional study. Patients A total of 2725 women aged 20 to 40 years with PCOS diagnosis were included. Interventions Serum AMH measurement by the Gen II (Beckman Coulter), the picoAMH (Ansh Labs), and the Elecsys (Roche) assays. Main outcome measures Age-specific percentile curves for all the assays and correlations between AMH, clinical, hormonal, and ultrasound characteristics. Results Age-related nomograms for the 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles of AMH were calculated using the Lambda-Mu-Sigma method for all the assays. AMH levels were significantly different between PCOS phenotypes. AMH levels were positively correlated to LH, LH/FSH ratio, testosterone, androstenedione, free androgen index, mean follicular number, and mean ovarian volume. Conclusion To our knowledge, this is the first study reporting age-specific percentile nomograms of serum AMH levels measured by the Gen II, the picoAMH, and the Elecsys assays in a large population of women with PCOS. These findings may help to interpret AMH levels in patients with PCOS and facilitate the use of AMH as a diagnostic tool across age ranges. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyse the effect of swimming goggles on swimming hydrodynamics by numerical simulations. An elite swimmer volunteered for this research. The swimmer's head was scanned both without goggles, and while wearing 3 different types of goggles (Nikko, Ankor and Swedish). Numerical simulations were conducted at 2 m/s with the Fluent code. The condition without goggles showed the highest viscous drag (1.65 N), followed by the Ankor (1.64 N), Swedish (1.63 N) and Nikko (1.62 N) goggles, respectively. The highest pressure drag was found in the situation without goggles (11.34 N), followed by the Ankor (10.87 N), Nikko (10.78 N) and Swedish (10.20 N) goggles. The condition without goggles presented the highest total drag (12.99 N), followed by the Ankor (12.52 N), Nikko (12.40 N) and Swedish (11.83 N) goggles. Thus, Swedish goggles yields the best hydrodynamics, followed by the Nikko and Ankor goggles and lastly without goggles. Thus, goggles minimise the swimmer's drag comparing to not wearing any. The design of the goggles may impose varying drag forces and therefore it is advised to use goggles at least in competition. [ABSTRACT FROM AUTHOR]

Objective: This study explored how personal therapy (PT) is experienced by psychotherapists, focussing on its positive and negative impact on clinical work as well as personal and professional development (PPD). The current meta‐analysis considered qualitative research studies focussing on therapists' experiences of the impact of their PT on their clinical activities and development. Method: A systematic review of the literature led to the identification of 21 published qualitative research studies. The findings from individual studies were subjected to grounded theory meta‐analysis. Results: Five clusters were identified: (1) PT helps to increase self‐awareness in general and within the therapeutic relations; (2) PT helps therapists to adopt a therapeutic approach by observing and experiencing the impact of therapeutic interventions; (3) PT helps to support patients in the therapeutic process on the basis of one's own experience of going through a therapeutic process; (4) PT helps therapists to become more confident and authentic because it fosters self‐acceptance; and (5) PT hinders clinical work and PPD through exposure to inadequate interventions and by stirring up personal issues. The four helpful clusters can be linked to the processes of personal growth, learning through observation and experience, experiential learning, and professional identity development, respectively. Conclusion: The findings of this study indicate that PT can have a helpful impact on clinical work and PPD through four processes that strengthen effective therapist skills, attitudes and ways of being. However, several studies demonstrate that the influence of PT on clinical work and PPD can also be experienced as complex, ambiguous and even harmful. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Is periconceptional multiple-micronutrient supplement (MMS) use including folic acid (FA) compared to FA use only associated with increased embryonic growth, development, and birth weight in a high-risk population? SUMMARY ANSWER Women with MMS intake show no significant differences in first-trimester morphological embryo development, but increased first-trimester embryonic growth trajectories and fewer neonates born small for gestational age (SGA), less than the 3rd percentile (

Objective: DYNC1H1 variants are involved on a disease spectrum from neuromuscular disorders to neurodevelopmental disorders. DYNC1H1‐related epilepsy has been reported in small cohorts. We dissect the electroclinical features of 34 patients harboring de novo DYNC1H1 pathogenic variants, identify subphenotypes on the DYNC1H1‐related epilepsy spectrum, and compare the genotype–phenotype correlations observed in our cohort with the literature. Methods: Patients harboring de novo DYNC1H1 pathogenic variants were recruited through international collaborations. Clinical data were retrospectively collected. Latent class analysis was performed to identify subphenotypes. Multivariable binary logistic regression analysis was applied to investigate the association with DYNC1H1 protein domains. Results: DYNC1H1‐related epilepsy presented with infantile epileptic spasms syndrome (IESS) in 17 subjects (50%), and in 25% of these individuals the epileptic phenotype evolved into Lennox–Gastaut syndrome (LGS). In 12 patients (35%), focal onset epilepsy was defined. In two patients, the epileptic phenotype consisted of generalized myoclonic epilepsy, with a progressive phenotype in one individual harboring a frameshift variant. In approximately 60% of our cohort, seizures were drug‐resistant. Malformations of cortical development were noticed in 79% of our patients, mostly on the lissencephaly–pachygyria spectrum, particularly with posterior predominance in a half of them. Midline and infratentorial abnormalities were additionally reported in 45% and 27% of subjects. We have identified three main classes of subphenotypes on the DYNC1H1‐related epilepsy spectrum. Significance: We propose a classification in which pathogenic de novo DYNC1H1 variants feature drug‐resistant IESS in half of cases with potential evolution to LGS (Class 1), developmental and epileptic encephalopathy other than IESS and LGS (Class 2), or less severe focal or genetic generalized epilepsy including a progressive phenotype (Class 3). We observed an association between stalk domain variants and Class 1 phenotypes. The variants p.Arg309His and p.Arg1962His were common and associated with Class 1 subphenotype in our cohort. These findings may aid genetic counseling of patients with DYNC1H1‐related epilepsy. [ABSTRACT FROM AUTHOR]

Background: This work aimed to determine the role and action points for the involvement of medical societies in the European Health Technology Assessment (EU HTA) Methods: An online pre-convention survey was developed addressing four areas related to the EU HTA: (i) medical societies' role; (ii) role of clinical guidelines; (iii) interface with the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS); and (iv) approaching 'best-available evidence' (BAE). A descriptive analysis of questionnaire outcomes was conducted to inform the European Access Academy (EAA) Fall Convention 2023. Within the working groups (WGs), action points were identified and prioritised. Results: A total of 57 experts from 15 countries responded to the survey. The WGs were attended by (i) 11, (ii) 10, (iii) 12, and (iv) 12 experts, respectively, representing a variety of national backgrounds and stakeholder profiles. The most relevant action points identified were as follows: (i) incorporation of clinical context into population, intervention, comparator, outcomes (PICO) schemes, (ii) timely provision of up-to-date therapeutic guidelines, (iii) ensuring the inclusion of MCBS insights into the EU HTA process, and (iv) considering randomized controlled trials (RCTs) as the gold standard and leveraging regulatory insights if development programs only include single-arm trials. Conclusions: The involvement of medical societies is a critical success factor for the EU HTA. The identified key action points foster the involvement of patient associations and medical societies. [ABSTRACT FROM AUTHOR]

Simple Summary: Hip dysplasia is prevalent among young dogs, affecting approximately 16% of the overall dog population, causing pain and exercise intolerance, and potentially leading to severe osteoarthritis. Current surgical interventions, such as pelvic osteotomies and total hip replacement, have limitations and a high level of complications. To address this, a personalized 3D-printed titanium implant was developed for dorsal acetabular rim extension (ACE-X), enhancing hip joint coverage and reducing hip laxity. In a previous short-term study spanning 3 months, the ACE-X implant demonstrated promising results: improved femoral head coverage, decreased pain-related activities based on owner questionnaires, and facilitated rapid recovery. This study aimed to offer a thorough analysis of clinical outcomes after a one-year follow-up period. The analysis encompassed radiographic measurements, force plate analysis, owner questionnaires, and an assessment of bone–implant osseointegration, as well as the identification and documentation of any complications encountered during the study period. By evaluating the long-term efficacy and safety of the ACE-X implant, this research contributes valuable insights into the management of hip dysplasia in dogs, potentially offering a novel and effective treatment option for this prevalent orthopedic condition. The acetabular rim extension (ACE-X) implant is a custom-made three-dimensionally printed titanium device designed for the treatment of canine hip dysplasia. In this study, 34 dogs (61 hips) underwent ACE-X implantation, and assessments were conducted using computed tomography, force plate analysis, Ortolani's test, and the Helsinki chronic pain index (HCPI) questionnaires at five intervals: the pre-operative day, the surgery day, and the 1.5-month, 3-month, and 12-month follow-ups. Statistically significant increases in femoral head coverage with a negative Ortolani subluxation test were observed immediately after surgery and persisted throughout the study. Osteoarthritis (OA) scores remained stable, but osteophyte size significantly increased between the surgery day and the 12-month follow-up, especially in hips with a baseline OA score of 2 compared to those with a score of 1. The force plate data showed no significant changes during the study. The HCPI demonstrated a significant decrease in pain score from pre-operative value to six-week follow-up and gradually decreased over time. Major complications were identified in six hips (9.8%) of four dogs. In conclusion, the ACE-X implant effectively increased femoral head coverage, eliminated subluxation, and provided long-term pain relief with minimal complications, benefiting over 90% of the study population. The study supports the ACE-X implant as a valuable alternative treatment for canine hip dysplasia. [ABSTRACT FROM AUTHOR]

Background Research on how tools can support coaching of residents is lacking. We hypothesized that an electronic assessment (EA) tool presently applied in selection for residency training, which measures cognitive capacities, personality, motivational drivers, and competencies, could be a valuable tool to support coaching of residents. Objective This study explored the value and limitations, as perceived by residents and coaches, of using the EA to facilitate a single coaching session. Methods This qualitative study took place in the East-Netherlands Training District from August 2022 to April 2023. Volunteer residents and professionally trained coaches engaged in a single coaching session, using the EA. A purposive sample of 7 residents in different training years from 3 specialties were recruited via the training secretariats. Individual interviews with residents were conducted 1 week and 3 months after the coaching session. Data collection ceased when data sufficiency was considered reached. A focus group interview was held with the 3 participating coaches. Thematic analysis was employed to identify themes. Results Participants considered the EA a supportive tool, but not the core focus in the coaching process. Coaching sessions remained guided by residents' individual needs. The EA was considered supportive in fostering residents' self-reflection and awareness, accelerating the coaching process by enhancing preparedness and fostering familiarity among residents and coaches. The perceived value of the EA for the coaching process was affected by residents' and coaches' attitudes toward the tool. Conclusions The EA played a supportive but nonprominent role in the coaching of residents. [ABSTRACT FROM AUTHOR]

Background: The cost of tobacco is one of the most reported reasons to quit smoking. The Netherlands increased tobacco taxes twice in the span of nine months: a €1 increase per pack in April 2020, and a €0.12 increase per pack in January 2021. This study examines to what extent people report to think about quitting due to the upcoming tax increase(s), as well as how it relates to their age, income or educational level. Additionally, we examined whether thinking about quitting was associated with quit intention and quit behaviour, and whether these associations were different for the two tax increases. Methods: Longitudinal data from the International Tobacco Control (ITC) Netherlands Surveys, Cohort 2 were used (N = 5919 observations; wave 1 (February – March 2020): n = 2051; wave 2 (September – November 2020): n = 1919; wave 3 (June – July 2021): n = 1949). Generalised Estimating Equation (GEE) regressions were fit to test the associations between thinking about quitting due to the tax increase and post-tax increases in quit intention, serious quit attempts, and quitting smoking (≤ 1 cigarette a month), as well as sociodemographic variables. Results: Circa half of the people who smoke reported thinking about quitting smoking due to the upcoming tax increase (Wave 1 = 51.3% (n = 1052); Wave 2 = 47.3% (n = 849)). Individuals who reported thinking about quitting smoking due to upcoming tax increase(s) were more likely to have increased their quit intention (aOR: 2.00, p ≤.001) or have carried out a serious quit attempt (aOR:1.48, p ≤.001) post-tax increase. More people attempted to quit smoking between wave 2 and 3 (post 2021 increase) than between wave 1 and 2 (post 2020 increase). We did not find an interaction effect between wave and thinking about quitting for quit intention, quit attempts, and quitting smoking. Conclusions: Tax increases stimulate people to think about quitting. Thinking about quitting due to an upcoming tax increase was associated with more positive quit intention and serious quit attempts. [ABSTRACT FROM AUTHOR]

Aim: To develop robust multivariable prediction models for non‐response to (1) submandibular botulinum neurotoxin A (BoNT‐A) injections and (2) concurrent submandibular and parotid (four‐gland) injections, to guide treatment decisions for drooling in children with neurodevelopmental disabilities, including cerebral palsy. Method: This was a retrospective cohort study including 262 children (155 males/107 females, median age 7 years 11 months [IQR 5 years 1 month], range 4 years 0 months – 17 years 11 months) receiving submandibular injections and 74 children (52 males/22 females, median age 7 years 7 months [IQR 4 years 3 months], range 4 years 9 months – 18 years 8 months) receiving four‐gland injections. Multivariable logistic regression analyses were used to estimate associations between candidate predictors and non‐response 8 weeks after injection. Results: Ninety‐six children (37%) were non‐responders to submandibular injections, for which developmental age was the strongest predictor (adjusted odds ratio [aOR] 2.13; 95% confidence interval [CI] 1.02–4.45 for developmental age <4 years or 4–6 years with IQ <70). Other characteristics that showed a trend towards an increased risk of non‐response were diagnosis, sex, and head position. Thirty‐four children (46%) were non‐responders to four‐gland injections, for which tongue protrusion (aOR 3.10; 95% CI 1.14–8.43) seemed most predictive, whereas multiple preceding submandibular injections (aOR 0.34; 95% CI 0.10–1.16) showed a trend towards being protective. Predictors were, however, unstable across different definitions of non‐response and both models (i.e. submandibular and four‐gland) had insufficient discriminative ability. Interpretation: Potential predictors of non‐response to BoNT‐A injections were identified. Nevertheless, the developed prediction models seemed inadequate for guidance of treatment decisions. What this paper adds: Developmental age seemed most predictive of non‐response to submandibular botulinum neurotoxin A injections.Non‐response to concurrent submandibular and parotid injections was best predicted by tongue protrusion and number of previous injections.Multivariable prediction models including these clinical characteristics were unable to discriminate well.Predictors differed when non‐response was defined using alternative outcome measures. [ABSTRACT FROM AUTHOR]

Plants are dependent on divisions of stem cells to establish cell lineages required for growth. During embryogenesis, early division products are considered to be stem cells, whereas during post-embryonic development, stem cells are present in meristems at the root and shoot apex. PLETHORA/AINTEGUMENTA-LIKE (PLT/AIL) transcription factors are regulators of post-embryonic meristem function and are required to maintain stem cell pools. Despite the parallels between embryonic and post-embryonic stem cells, the role of PLTs during early embryogenesis has not been thoroughly investigated. Here, we demonstrate that the PLT regulome in the zygote, and apical and basal cells is in strong congruence with that of post-embryonic meristematic cells. We reveal that out of all six PLTs, only PLT2 and PLT4/BABY BOOM(BBM) are expressed in the zygote, and that these two factors are essential for progression of embryogenesis beyond the zygote stage and first divisions. Finally, we show that other PLTs can rescue plt2 bbm defectswhen expressed fromthe PLT2 andBBMpromoters, establishing upstream regulation as a key factor in early embryogenesis. Our data indicate that generic PLT factors facilitate early embryo development in Arabidopsis by induction of meristematic potential. [ABSTRACT FROM AUTHOR]

BACKGROUND: Overweight and obesity impose a considerable individual and social burden, and the urban environments might encompass factors that contribute to obesity. Nevertheless, there is a scarcity of research that takes into account the simultaneous interaction of multiple environmental factors. OBJECTIVES: Our objective was to perform an exposome-wide association study of body mass index (BMI) in a multicohort setting of 15 studies. METHODS: Studies were affiliated with the Dutch Geoscience and Health Cohort Consortium (GECCO), had different population sizes (688–141,825), and covered the entire Netherlands. Ten studies contained general population samples, others focused on specific populations including people with diabetes or impaired hearing. BMI was calculated from self-reported or measured height and weight. Associations with 69 residential neighborhood environmental factors (air pollution, noise, temperature, neighborhood socioeconomic and demographic factors, food environment, drivability, and walkability) were explored. Random forest (RF) regression addressed potential nonlinear and nonadditive associations. In the absence of formal methods for multimodel inference for RF, a rank aggregation-based meta-analytic strategy was used to summarize the results across the studies. RESULTS: Six exposures were associated with BMI: five indicating neighborhood economic or social environments (average home values, percentage of high-income residents, average income, livability score, share of single residents) and one indicating the physical activity environment (walkability in 5-km buffer area). Living in high-income neighborhoods and neighborhoods with higher livability scores was associated with lower BMI. Nonlinear associations were observed with neighborhood home values in all studies. Lower neighborhood home values were associated with higher BMI scores but only for values up to e300,000. The directions of associations were less consistent for walkability and share of single residents. DISCUSSION: Rank aggregation made it possible to flexibly combine the results from various studies, although between-study heterogeneity could not be estimated quantitatively based on RF models. Neighborhood social, economic, and physical environments had the strongest associations with BMI. [ABSTRACT FROM AUTHOR]

Previous studies have shown that mothers of naturally conceived dizygotic (DZ) twins tend to be taller, older, and smoke more than mothers of naturally conceived monozygotic (MZ) twin and mothers of singletons. Here, we investigate whether mothers of naturally conceived DZ twins differ from mothers who conceived their DZ twins after medically assisted reproduction (MAR) in eight maternal traits related to fertility based on observational survey data. We include data from 33,648 mothers from the Netherlands Twin Register (NTR) and 1660 mothers of twins from the Norwegian Mother, Father and Child Cohort Study (MoBA). We contrast mothers of naturally conceived DZ twins with mothers of MAR DZ twins. Next, we further segment the MAR group into mothers who underwent hormonal induction of ovulation but not in vitro fertilization (IVF) and those who IVF twins, comparing them both to each other and against the mothers of naturally conceived DZ twins. Mothers of naturally conceived DZ twins smoke more often, differ in body composition, have a higher maternal age and have more offspring before the twins than mothers of MZ twins. Compared to MAR DZ twin mothers, mothers of naturally conceived DZ twins have fewer miscarriages, lower maternal age and increased height, more offspring and are more often smokers. BMI before the twin pregnancy is similar in both natural and MAR DZ twin mothers. Mothers who received hormonal induction of ovulation (OI) have a lower maternal age, fewer miscarriages, and a higher number of offspring before their twin pregnancy than twin mothers who received IVF and/or intracytoplasmic sperm injection (ICSI) treatments. Our study shows that twin mothers are a heterogenous group and the differences between twin mothers should be taken into account in epidemiological and genetic research that includes twins. [ABSTRACT FROM AUTHOR]

Philosophers and linguists currently lack the means to reliably identify evaluative concepts and measure their evaluative intensity. Using a corpus-based approach, we present a new method to distinguish evaluatively thick and thin adjectives like 'courageous' and 'awful' from descriptive adjectives like 'narrow,' and from value-associated adjectives like 'sunny.' Our study suggests that the modifiers 'truly' and 'really' frequently highlight the evaluative dimension of thick and thin adjectives, allowing for them to be uniquely classified. Based on these results, we believe our operationalization may pave the way for a more quantitative approach to the study of thick and thin concepts. [ABSTRACT FROM AUTHOR]

Personalized news experiences powered by recommender systems permeate our lives and have the potential to influence not only our opinions, but also our decisions. At the same time, the content and viewpoints contained within news recommendations are driven by multiple factors, including both personalization and editorial selection. Explanations could help users gain a better understanding of the factors contributing to the news items selected for them to read. Indeed, recent works show that explanations are essential for users of news recommenders to understand their consumption preferences and set intentions in line with their goals, such as goals for knowledge development and increased diversity of content or viewpoints. We give examples of such works on explanation and interactive interface interventions which have been effective in influencing readers' consumption intentions and behaviors in news recommendations. However, the state‐of‐the‐art in news recommender systems currently fall short in terms of evaluating such interventions in live systems, limiting our ability to measure their true impact on user behavior and opinions. To help understand the true benefit of these interfaces, we therefore call for improving the realism of studies for news. [ABSTRACT FROM AUTHOR]

The central question of our study is which determinants drive smoke alarm ownership and intention to purchase one, and whether we can increase smoke alarm ownership by addressing these determinants in a communication‐based intervention. We first made an inventory of possible determinants for smoke alarm prevention by consulting prominent prevention behavior theories protection motivation theory and Health Belief Model and other relevant literature. We expanded this list of determinants based on interviews (n = 15) and used survey data representative for the Netherlands to decide to focus on smoke alarm ownership (rather than installation or maintenance). We then tested the determinants of smoke alarm ownership and buying intention in a survey (n = 622). Based on these results, we ran an A/B test (n = 310) of two messages to stimulate smoke alarm ownership: one emphasized the determinants we found to be strong predictors in the survey (know‐how, social norm, annoyance) and one emphasized typical determinants that are often addressed in campaigns but were poor predictors in the survey (vulnerability, severity, benefits). Results showed that the message based on the strong determinants resulted in a significant increase in smoke alarm ownership (9.1%) compared to the control group (0.9%; p = 0.027), while the message using the typical determinants did not lead to significant effects. Taken together, our results give a promising direction for interventions to increase smoke alarm ownership, and above all, show that a comprehensive problem analysis for a specific target behavior is a necessary step to induce behavioral change. [ABSTRACT FROM AUTHOR]

Purpose: Today's diet consists of a substantial proportion of ultra-processed foods (UPF), especially in women with overweight and obesity in the reproductive period. High UPF intake results in an inadequate and unbalanced diet leading to derangements of several metabolic pathways detrimental to pregnancy and birth outcomes. Therefore, we aim to investigate whether UPF intake in the periconceptional period affects total homocysteine plasma levels (tHcy). Methods: 1532 participants were included from the prospective Rotterdam Periconceptional Cohort. UPF intake was calculated using Food Frequency Questionnaires including items classified as 4 in the Nova classification, and tHcy was measured by using liquid chromatography-tandem mass spectrometry system, with an interassay coefficient of variation of < 5.5%. Multivariable linear regression modeling was used and adjusted for covariates and significant interaction terms. Results: Women with overweight or obesity showed significantly higher percentage of UPF intake (respectively, 50.3 and 51.3%) and higher tHcy (respectively, 6.6 and 6.3 µmol/L, Kruskal–Wallis test; respectively, p < 0.001 and p = 0.04) compared to women with normal BMI (UPF intake: 46.8%, tHcy: 6.1 µmol/L). A 10% higher intake of UPF was associated with an increase in tHcy (adjusted: β = 1.31, 95% CI = 0.38–2.23). Analysis stratified for BMI classification showed comparable associations in normal weight participants (adjusted: β = 1.07, 95% CI = 0.06–2.07); however, no significant association in participants with overweight (adjusted: β = 0.06, 95% CI = − 0.95–1.07) and obesity (adjusted: β = 1.70, 95% CI = − 0.52–3.92) was shown. Conclusion: This study showed that a higher intake of UPF is associated with increased tHcy. Better knowledge and awareness of the nutritional quality of the diet in the periconceptional period may contribute to 1-CM and subsequently improve pregnancy course and outcome. Trial registration number and date: NTR4356, November 2010. [ABSTRACT FROM AUTHOR]

Precise regulation of gene expression is important for correct neurodevelopment. 9q34.3 deletions affecting the EHMT1 gene result in a syndromic neurodevelopmental disorder named Kleefstra syndrome. In contrast, duplications of the 9q34.3 locus encompassing EHMT1 have been suggested to cause developmental disorders, but only limited information has been available. We have identified 15 individuals from 10 unrelated families, with 9q34.3 duplications <1.5 Mb in size, encompassing EHMT1 entirely. Clinical features included mild developmental delay, mild intellectual disability or learning problems, autism spectrum disorder, and behavior problems. The individuals did not consistently display dysmorphic features, congenital anomalies, or growth abnormalities. DNA methylation analysis revealed a weak DNAm profile for the cases with 9q34.3 duplication encompassing EHMT1, which could segregate the majority of the affected cases from controls. This study shows that individuals with 9q34.3 duplications including EHMT1 gene present with mild non‐syndromic neurodevelopmental disorders and DNA methylation changes different from Kleefstra syndrome. [ABSTRACT FROM AUTHOR]

Recently, OTULIN haploinsufficiency was linked to enhanced susceptibility to Staphylococcus aureus infections accompanied by local necrosis and systemic inflammation. The pathogenesis observed in haploinsufficient patients differs from the hyperinflammation seen in classical OTULIN-related autoinflammatory syndrome (ORAS) patients and is characterized by increased susceptibility of dermal fibroblasts to S. aureus alpha toxin-inflicted cytotoxic damage. Immunological abnormalities were not observed in OTULIN haploinsufficient patients, suggesting a non-hematopoietic basis. In this research report, we investigated an Otulin+/- mouse model after in vivo provocation with lipopolysaccharide (LPS) to explore the potential role of hematopoietic-driven inflammation in OTULIN haploinsufficiency. We observed a hyperinflammatory signature in LPS-provoked Otulin+/- mice, which was driven by CD64+ monocytes and macrophages. Bone marrow-derived macrophages (BMDMs) of Otulin+/- mice demonstrated higher proinflammatory cytokine secretion after in vitro stimulation with LPS or polyinosinic:polycytidylic acid (Poly(I:C)). Our experiments in full and mixed bone marrow chimeric mice suggest that, in contrast to humans, the observed inflammation was mainly driven by the hematopoietic compartment with cell-extrinsic effects likely contributing to inflammatory outcomes. Using an OTULIN haploinsufficient mouse model, we validated the role of OTULIN in the regulation of environmentally directed inflammation. [ABSTRACT FROM AUTHOR]

Background: Sepsis, a life-threatening condition caused by the dysregulated host response to infection, is a major global health concern. Understanding the impact of viral or bacterial pathogens in sepsis is crucial for improving patient outcomes. This study aimed to investigate the human cytomegalovirus (HCMV) seropositivity as a risk factor for development of sepsis in patients with COVID-19. Methods: A multicenter observational study enrolled 95 intensive care patients with COVID-19-induced sepsis and 80 post-surgery individuals as controls. HCMV serostatus was determined using an ELISA test. Comprehensive clinical data, including demographics, comorbidities, and 30-day mortality, were collected. Statistical analyses evaluated the association between HCMV seropositivity and COVID-19 induced sepsis. Results: The prevalence of HCMV seropositivity did not significantly differ between COVID-19-induced sepsis patients (78%) and controls (71%, p = 0.382) in the entire cohort. However, among patients aged ≤60 years, HCMV seropositivity was significantly higher in COVID-19 sepsis patients compared to controls (86% vs 61%, respectively; p = 0.030). Nevertheless, HCMV serostatus did not affect 30-day survival. Discussion: These findings confirm the association between HCMV seropositivity and COVID-19 sepsis in non-geriatric patients. However, the lack of an independent effect on 30-day survival can be explained by the cross-reactivity of HCMV specific CD8+ T-cells towards SARS-CoV-2 peptides, which might confer some protection to HCMV seropositive patients. The inclusion of a postsurgery control group strengthens the generalizability of the findings. Further research is needed to elucidate the underlying mechanisms of this association, explore different patient populations, and identify interventions for optimizing patient management. Conclusion: This study validates the association between HCMV seropositivity and severe COVID-19-induced sepsis in non-geriatric patients, contributing to the growing body of evidence on viral pathogens in sepsis. Although HCMV serostatus did not independently influence 30-day survival, future investigations should focus on unraveling the intricate interplay between HCMV, immune responses, and COVID-19. These insights will aid in risk stratification and the development of targeted interventions for viral sepsis. [ABSTRACT FROM AUTHOR]

The autosomal recessive defect of aromatic L‐amino acid decarboxylase (AADC) leads to a severe neurological disorder with manifestation in infancy due to a pronounced, combined deficiency of dopamine, serotonin and catecholamines. The success of conventional drug treatment is very limited, especially in patients with a severe phenotype. The development of an intracerebral AAV2‐based gene delivery targeting the putamen or substantia nigra started more than 10 years ago. Recently, the putaminally‐delivered construct, Eladocagene exuparvovec has been approved by the European Medicines Agency and by the British Medicines and Healthcare products Regulatory Agency. This now available gene therapy provides for the first time also for AADC deficiency (AADCD) a causal therapy, leading this disorder into a new therapeutic era. By using a standardized Delphi approach members of the International Working Group on Neurotransmitter related Disorders (iNTD) developed structural requirements and recommendations for the preparation, management and follow‐up of AADC deficiency patients who undergo gene therapy. This statement underlines the necessity of a framework for a quality‐assured application of AADCD gene therapy including Eladocagene exuparvovec. Treatment requires prehospital, inpatient and posthospital care by a multidisciplinary team in a specialized and qualified therapy center. Due to lack of data on long‐term outcomes and the comparative efficacy of alternative stereotactic procedures and brain target sites, a structured follow‐up plan and systematic documentation of outcomes in a suitable, industry‐independent registry study are necessary. [ABSTRACT FROM AUTHOR]

Succinic semialdehyde dehydrogenase deficiency (SSADHD) is a rare neurometabolic disorder caused by disruption of the gamma‐aminobutyric acid (GABA) pathway. A more detailed understanding of its pathophysiology, beyond the accumulation of GABA and gamma‐hydroxybutyric acid (GHB), will increase our understanding of the disease and may support novel therapy development. To this end, we compared biochemical body fluid profiles from SSADHD patients with controls using next‐generation metabolic screening (NGMS). Targeted analysis of NGMS data from cerebrospinal fluid (CSF) showed a moderate increase of aspartic acid, glutaric acid, glycolic acid, 4‐guanidinobutanoic acid, and 2‐hydroxyglutaric acid, and prominent elevations of GHB and 4,5‐dihydroxyhexanoic acid (4,5‐DHHA) in SSADHD samples. Remarkably, the intensities of 4,5‐DHHA and GHB showed a significant positive correlation in control CSF, but not in patient CSF. In an established zebrafish epilepsy model, 4,5‐DHHA showed increased mobility that may reflect limited epileptogenesis. Using untargeted metabolomics, we identified 12 features in CSF with high biomarker potential. These had comparable increased fold changes as GHB and 4,5‐DHHA. For 10 of these features, a similar increase was found in plasma, urine and/or mouse brain tissue for SSADHD compared to controls. One of these was identified as the novel biomarker 4,5‐dihydroxyheptanoic acid. The intensities of selected features in plasma and urine of SSADHD patients positively correlated with the clinical severity score of epilepsy and psychiatric symptoms of those patients, and also showed a high mutual correlation. Our findings provide new insights into the (neuro)metabolic disturbances in SSADHD and give leads for further research concerning SSADHD pathophysiology. [ABSTRACT FROM AUTHOR]