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A collection of Open Access and Embargoed publications from Utrecht University Repository. For an explanation on how and where to find an Open Access version of a publication see the information on this page.

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    Proteomics signature of moderate-to-vigorous physical activity and risk of multimorbidity of cancer and cardiometabolic diseases
    (Springer Nature, 2026-03-23) Stein, Michael J.; Baurecht, Hansjörg; Bohmann, Patricia; Cordova, Reynalda; Ferrari, Pietro; Fervers, Béatrice; Friedenreich, Christine M.; Gunter, Marc J.; Peruchet-Noray, Laia; Wu, Diana; Onland-Moret, Charlotte; Sánchez, Maria José; Chirlaque, María Dolores; Leitzmann, Michael F.; Viallon, Vivian; Freisling, Heinz; Data gedreven innovatie; Circulatory Health; JC onderzoeksprogramma Cardiovascular Health
    Background: Moderate-to-vigorous physical activity (MVPA) is inversely associated with risks of cancer, cardiovascular diseases (CVD), type 2 diabetes (T2D), and their co-occurrence, defined as multimorbidity; however, the underlying biological pathways remain unclear. Methods: In 33,806 UK Biobank participants with 2911 measured blood proteins, a proteomic signature of MVPA was derived with linear and LASSO regressions. Multivariable Cox models, adjusted for MVPA, estimated prospective associations with cancer, CVD, T2D, and multimorbidity. Results: We show that after multiple testing corrections, 220 proteins are retained in the MVPA signature. Proteins related to food intake, metabolism, and cell growth (e.g., LEP, MSTN) are inversely associated, while those involved in immune cell migration and musculoskeletal integrity (e.g., integrins, COMP) are positively associated with MVPA. Several proteins positively associated with MVPA are inversely associated with disease risk (e.g., integrins, CLEC4A for cancer; LPL, LEP for T2D), while proteins negatively associated with MVPA are positively associated with disease risk (e.g., CD38, TGFA for CVD). The proteomic signature score is inversely associated with cancer risk (hazard ratio per interquartile range: 0.87; 95% confidence interval: 0.78, 0.96) and T2D (0.66; 0.60, 0.72). For multimorbidity, proteins inversely related to MVPA align with expected risk patterns (e.g., GGT1, HR: 1.32; 95% CI: 1.12, 1.57), but the proteomic signature score is not associated. Conclusions: This study identifies several proteins associated with MVPA that are also associated with cancer, CVD, T2D, and the multimorbidity of these conditions. Further studies investigating the causal nature of these associations are welcome.
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    Anatomy and Cell Biology of Autism Spectrum Disorder: Lessons from Human Genetics
    (Springer, 2017) Kleijer, Kristel T E; Huguet, Guillaume; Tastet, Julie; Bourgeron, Thomas; Burbach, J P H; Translational Neuroscience; Brain; TN Onderwijs; Regenerative Medicine and Stem Cells
    Until recently autism spectrum disorder (ASD) was regarded as a neurodevelopmental condition with unknown causes and pathogenesis. In the footsteps of the revolution of genome technologies and genetics, and with its high degree of heritability, ASD became the first neuropsychiatric disorder for which clues towards molecular and cellular pathogenesis were uncovered by genetic identification of susceptibility genes. Currently several hundreds of risk genes have been assigned, with a recurrence below 1% in the ASD population. The multitude and diversity of known ASD genes has extended the clinical notion that ASD comprises very heterogeneous conditions ranging from severe intellectual disabilities to mild high-functioning forms. The results of genetics have allowed to pinpoint a limited number of cellular and molecular processes likely involved in ASD including protein synthesis, signal transduction, transcription/chromatin remodelling and synaptic function all playing an essential role in the regulation of synaptic homeostasis during brain development. In this context, we highlight the role of protein synthesis as a key process in ASD pathogenesis as it might be central in synaptic deregulation and a potential target for intervention. These current insights should lead to a rational design of interventions in molecular and cellular pathways of ASD pathogenesis that may be applied to affected individuals in the future.
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    Molluscivorous red knots rapidly adjust to a plant diet
    (Company of Biologists Ltd, 2026-04) De Wilde, Marie; Maarsingh, Berber; de Monte, Luc G G; Dekinga, Anne; Bijleveld, Allert I; Kressin, Hidde; Zomer, Aldert L; Piersma, Theunis; Infectious Diseases and Immunology - KLIF; Klinische infectiologie en microb. lab.
    Dietary flexibility is key to adjusting to environmental change. In Mauritania, the seemingly obligatory molluscivorous red knots Calidris canutus were observed to eat seagrass rhizomes. To study the ability of knots to live on plant material, we performed a diet-change experiment on captive individuals. Two groups of five were fed protein-rich pellets for 13 weeks, then plant-based pellets for 6 weeks, then reversed back to protein-rich pellets for 4.5 weeks. During the first days following the shift to the plant diet, body mass declined by 14% before increasing and stabilizing to lower levels. Faecal colour changed from green (i.e. gall, suggesting starvation) to brown and was produced in larger quantities when the birds ate plant pellets. These experimental data prove that knots can indeed live on a plant-based diet, with the observed changes suggesting that adjustments of the digestive system, i.e. gut morphology and microbiome, take only a few days.
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    The definition of response and inadequate response to topical corticosteroid treatment in atopic dermatitis and related skin inflammatory diseases: A GA2LEN ADCARE statement paper
    (Elsevier, 2026-05) Zuberbier et al., Torsten; de Bruin-Weller, Marjolein; MS Dermatologie/Allergologie; Infection & Immunity
    Background Topical corticosteroids (TCS) remain the first-line treatment for atopic dermatitis (AD) and related inflammatory skin diseases, yet no standardized definition of response exists. This gap contributes to heterogeneity in clinical practice and complicates trial design. We therefore aimed to develop consensus-based definitions of response and inadequate response to TCS therapy through a structured international eDelphi process. Methods A PubMed search (1974–July 2025) identified 403 relevant publications. Candidate statements were drafted from the evidence and refined by the ADCARE Steering Committee, categorized into 3 domains (status quo, unmet need, proposals), and evaluated in a three-round eDelphi survey among certified ADCARE members. Eighty-four dermatologists and allergists from 32 countries participated (Round 1 response rate 98%; Round 2, 80%; Round 3, 76%). Statements were rated on a 5-point Likert scale; consensus was defined as ≥75% agreement (scores 4 or 5). Results In total, 66 of 83 statements reached consensus. In the status quo domain, agreement centred on baseline severity, body surface area, and anatomical site as guiding factors for TCS choice, with potency and licensed duration considered central to safe prescribing. In the unmet-need domain, experts highlighted the absence of standardized definitions, variability in monitoring and escalation strategies, and gaps in long-term evidence and integration of patient-reported outcomes. In the proposal domain, consensus supported relative improvement thresholds (≥50% in EASI, SCORAD, itch NRS, IGA, PGA, POEM) and 14 days as a meaningful evaluation point. Absolute cut-offs, very short (7 days) or long (3 months) timeframes, and rigid escalation rules did not achieve consensus. These parameters were synthesized into concise and extended definitions of TCS response and inadequate response. Conclusions This GA2LEN ADCARE initiative represents the first international consensus on defining TCS response and inadequate response, offering a framework to harmonize clinical practice, enhance trial comparability, and support guideline development.
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    Moving Through The Day: The 24-hour physical activities throughout the life course of people with cerebral palsy
    (Utrecht University, 2026-05-19) van Rijssen, Ilse; Revalidatiegeneeskunde Onderzoek; Gorter, Jan Willem; Visser-Meilij, Anne; Verschuren, Olaf
    This thesis provides a comprehensive life course perspective on the 24-hour physical activities – sleep, physical activity, and sedentary behaviour – of individuals with cerebral palsy (CP). By integrating objective measurements with lived experiences, it advances our understanding of daily activity patterns in both children and adults with CP. We highlight implications for care, research, and clinical practice. Overall, the findings demonstrate that challenges in the 24-hour physical activities are present across the lifespan. Adults with CP report poorer sleep quality compared with reference populations, and experience difficulties in balancing rest and activity, independent of age or physical function. Sleep, physical activity, and fatigue are interrelated and influenced by a complex interplay of physical, mental, and environmental factors. In children with CP, associations between sleep, physical activity, and sensory processing were limited or absent, suggesting that relationships between these activities and domains are complex and not easily captured when studied in isolation. A central message of this thesis is that adopting a life course perspective is essential. CP is not a childhood condition, but a lifelong neurological disorder with changing manifestations and needs. With age, individuals with CP often face new or increased challenges, including fatigue, reduced participation, pain and changes in sleep and physical activity. These neurological and systemic challenges are increasingly recognized in adults with CP. Despite this, research and healthcare remain largely focused on childhood. The findings support viewing sleep, physical activity, and rest as an integrated 24-hour continuum rather than separate behaviours. Rest and sedentary time are not inherently negative but can play a restorative role in maintaining energy balance and participation. Supporting individuals with CP therefore requires attention to the interplay between activity and rest, tailored to personal context and life circumstances. Finally, this thesis demonstrates the value of device-based assessments for capturing detailed and fluctuating patterns in 24-hour physical activities that are often missed by questionnaires. Such methods provide important opportunities for monitoring daily behaviours and supporting self-management in individuals with CP. However, challenges remain in translating these tools into clinical practice. Data interpretation can be time-consuming, and further improvements in usability and clinical integration are needed. In conclusion, improving outcomes for individuals with CP requires a shift towards a holistic, lifespan-oriented approach that integrates sleep, activity, and rest; leverages emerging measurement techniques; and acknowledges the evolving needs of individuals with CP across their lives.