Herein, we molecularly characterize the novel human term trophoblast cell line TB/SVTERT350 and show that it meets the criteria for trophoblast identity and subtype specification. TB/SVTERT350, cultured under stemness conditions in 2D or 3D, express trophoblast progenitor markers such as E-cadherin, TEAD4 and YAP1 and develop into CGβ-producing syncytiotrophoblast and HLA-G-expressing extravillous trophoblasts in the respective differentiation media. Expanding TB/SVTERT350 organoids share structural similarities with primary trophoblast organoids and express NOTCH1 suggesting that the cell line exhibits phenotypic traits of proximal cell column trophoblasts. In summary, TB/SVTERT350 could represent a reliable model for studying mechanisms of placental growth and differentiation.

BACKGROUND:Non-communicable diseases (NCDs) remain a major public health burden, despite widely established preventive interventions. Digital Health solutions focusing on prevention are often fragmented and weakly linked to evidence-based guidelines. OBJECTIVES:This work aimed to develop a systematic approach for translating guideline-based health indicators into the PreNUDGE ecosystem, a digital prevention platform. METHODS:Clinical guidelines for four NCDs were screened to identify prevention-relevant indicators suitable for self-reporting, which were structured using a standardized schema, aligned with HL7 FHIR principles and prepared for integration into qualified apps within the PreNUDGE platform. RESULTS:A core set of disease-specific health indicators was derived and is ready to be translated into apps and ready to be implemented in the PreNUDGE ecosystem. CONCLUSION:The approach demonstrates the feasibility of operationalizing guideline-based health indicators within a digital prevention platform to support personalized prevention and public health analyses.

Rift Valley fever virus (RVFV) is a mosquito-borne Phlebovirus and zoonotic pathogen affecting maternal-fetal health. Vertical transmission is linked to miscarriage and severe fetal outcomes, but mechanisms of placental pathogenesis remain unclear. We used first-trimester human trophoblast stem cells (hTSCs) to model infection at the maternal-fetal interface. Immunofluorescence, qRT-PCR, western blotting, and single-cell transcriptomics showed that hTSCs are highly susceptible to RVFV. Strand-specific viral transcriptomics confirmed the ambisense S segment and revealed preferential transcription of the M and S segments over L. RVFV induced G1 arrest, impairing trophoblast proliferation and differentiation, and drove widespread transcriptional reprogramming, including strong interferon lambda 1 (IFNL1) but modest type I interferon responses, and dysregulation of inflammatory and preeclampsia-associated genes such as RUNX1 and TGFBRAP1. Recombinant IFN-λ pretreatment reduced RVFV protein expression, highlighting hTSCs as a robust model and IFN-λ as a promising antiviral strategy.

Introduction Non-communicable diseases (NCDs) currently contribute to over 50% of the global disease burden. Digital tools bear the potential to mitigate the risk of NCDs by facilitating personalised, preventive healthcare. It is therefore pertinent to examine the specific components that contribute to the success or constrain the impact of digital health interventions (DHIs), with particular attention to the sustainability of their long-term effects. Additionally, it is important to provide an up-to-date perspective on emerging interventions and technologies that have not yet been comprehensively addressed in the literature. This protocol defines the methodology for an umbrella review to synthesise the available high-quality evidence from systematic reviews and meta-analyses regarding effectiveness of DHIs in influencing the primary prevention of NCDs.Methods and analysis Using a rigorous search strategy, the subsequent databases will be searched in December 2025: MEDLINE, Web of Science, CINAHL, Embase, Scopus and Epistemonikos. Following the Joanna Briggs Institute (JBI) methodology, the selected literature will be screened based on predefined inclusion criteria. This includes systematic reviews and meta-analyses published within the last 5 years, without restrictions on country or language, that evaluate the effectiveness of any DHI aimed at the primary prevention of NCDs. Suitable full-text articles will be extracted by four researchers and independently assessed for methodological quality by two researchers using the AMSTAR-2 (A Measurement Tool to Assess Systematic Reviews) tool. The results will be presented in a summary table aligned with the review question and subquestions, accompanied by a narrative synthesis that explores the findings and their relevance to the research aims.Ethics and dissemination Ethical approval is not required as no primary data will be collected. The findings of this umbrella review will be published in a peer-reviewed journal and presented at academic conferences.PROSPERO registration number CRD420251139744.

Background and Objectives: Functional decline and sarcopenia are major aging-related concerns. While protein intake is known to influence muscle health, its longitudinal impact on strength and physical function across age and gender remains underexplored. We assessed whether low protein intake correlate with future onset of low handgrip strength (HGS) and physical impairments in older adults using SHARE data. Methods: We analyzed 38,073 adults aged ≥50 years from 27 European countries using SHARE Waves 8 (2019/20) and 9 (2021/22). A protein intake index was derived from the frequency of consuming dairy, legumes/eggs, and meat/fish/poultry. Low intake was defined as the lowest decile. Logistic regression models, adjusted for age, gender, country, and baseline health, examined associations with low HGS and ten physical difficulties, stratified by age (50-65 vs. ≥66 years) and gender. Results: Low protein intake is associated with higher odds of low HGS in men (OR = 1.39 for 50-65; OR = 1.35 for ≥66) and older women (OR = 1.21). It was also associated with higher odds of mobility-related limitations, including walking 100 m (ORs = 1.25-1.53), stooping/kneeling (ORs = 1.20-1.19 in women), and reaching overhead (ORs = 1.19-1.33). Strength-related tasks, such as pushing/pulling large objects were more affected in men (ORs = 1.44 and 1.21). Notably, women aged 50-65 had over twice the odds of toileting difficulty (OR = 2.27) and significantly higher odds of difficulty shopping (OR = 1.65). These patterns highlight gender- and age-specific vulnerabilities. Conclusions: Low protein intake is associated with modest but consistent increases in the risk of reduced muscle strength and functional difficulties in older adults. Tailored nutritional strategies may mitigate age- and gender-specific risks to physical independence.

Introduction Approximately one in five workers in Europe is engaged in shift work. Studies reveal that night shift work leads to an increased risk of overweight, obesity and related diseases. Yet, the biological and behavioural mechanisms underlying these associations are not fully understood. The cross-sectional and mechanistic studies within the European SHIFT2HEALTH project aim to investigate biological, behavioural and psychosocial key risk factors responsible for the association between night work and obesity across five European countries. Methods A multi-centric cross-sectional study is designed to unravel obesogenic risk factors, eating habits and sleep patterns in night shift workers and day workers from the health- and various industrial sectors. Recruitment takes place in Austria, Denmark, Germany, Poland, and the Netherlands, aiming at 500 night shift workers and 500 day workers. Anthropometric measurements, sensory perception and food preference tests are performed, alongside extensive questionnaires. In addition, biological samples (blood, hair, urine, faeces) are collected for biomarker measurements of inflammation, oxidative stress, glycaemic and lipaemic parameters, for microbiome and metabolomics analyses and chronotype assessment. In a nested mechanistic study, night shift workers (N=200) recruited in Austria and in the Netherlands, additionally collect urine samples from all voids over 24 hours during a day shift and a night shift, as well as dried blood spots and tongue swabs at four time points and undergo continuous sleep, activity and light exposure monitoring through actigraphy. The association between night shift work and its metrics with levels of pre-obesity biomarkers will be evaluated in crude and multivariable-adjusted regression models, adjusting for potential confounders. Stratified analyses by age, gender, sector and chronotype will be conducted. Conclusion In the cross-sectional and mechanistic studies of the SHIFT2HEALTH project, biological, behavioural and psychosocial factors of night shift workers will be compared with those of day workers across sectors. The outcomes of these studies will serve as a basis for future intervention studies and, together, will contribute to the development of strategies to prevent and reduce overweight and obesity with the aim to improve the health and wellbeing of night shift workers. Trial registration: clinicaltrials.gov, ID: NCT06288568

Abstract Background Night shift workers are more likely to exhibit unfavorable dietary behaviors than day workers. However, these differences remain insufficiently explored within the European workforce. This study aims to examine differences in dietary behaviors (food intake frequency, eating frequency) by night shift exposure (history, frequency, duration) to investigate eating frequency, meal timing, and food choice determinants during night shifts, and to explore gender differences across Europe. Methods Data were collected via an online survey (May 2024-January 2025) in eight countries (Austria, Germany, Denmark, Greece, Italy, the Netherlands, Poland, Spain). Participants self-reported sociodemographics, occupational sector, current work schedules, shift work history, lifestyle characteristics, and dietary behaviors. A shortened Food Frequency Questionnaire (FFQ) assessed dietary intake, alongside questions on eating rate and frequency on work and non-work-days. Current night shift workers additionally reported eating frequency, timing, and food choice determinants during night shifts. Analyses compared dietary behaviors by night shift exposure (current, former, vs. day worker). Among current night shift workers, associations with night shift frequency (nights/month) and duration (years) were examined. Secondary analyses were stratified by gender. Results A total of 6,260 individuals were included (mean age 40.7, SD 10.7; 50.5% female). Overall, 60.4% were current night shift workers, 19.6% former night shift workers, and 20% day workers. Compared to day workers, current night shift workers reported significantly faster eating rates (OR = 1.21, 95% CI: 1.06–1.37), more frequent intake of sugar-sweetened (OR = 1.30, 95% CI: 1.14–1.48) and caffeinated beverages (OR = 1.14, 95% CI: 1.01–1.30), and lower fruit intake (OR = 0.87, 95% CI: 0.77–0.98). Higher monthly night shift load and longer duration of night work were associated with less favorable dietary patterns. Most current night shift workers reported one to two eating occasions per night, typically at the beginning or middle of their shift. Food choices were primarily driven by appetite, time, and food availability. Gender differences were observed only in food choice determinants. Conclusions Night shift and day workers in Europe showed differences in dietary behaviors, particularly in sugar-sweetened beverage intake and eating rate. These findings highlight the need for targeted interventions to promote healthy eating among shift working populations.

During the first stages of embryonic development, the placenta develops under very low oxygen tension (∼1%-2% O2), so we sought to determine the regulatory role of oxygen in human trophoblast stem cells (hTSCs). We find that low oxygen promotes hTSC self-renewal but inhibits differentiation to syncytiotrophoblast (STB) and extravillous trophoblast (EVT). The transcription factor GCM1 (glial cell missing transcription factor 1) is downregulated in low oxygen, and concordantly, there is substantial reduction of GCM1-regulated genes in hypoxic conditions. Knockout of GCM1 in hTSC likewise impaired EVT and STB formation. Treatment with a phosphatidylinositol 3-kinase (PI3K) inhibitor reported to reduce GCM1 protein levels likewise counteracts spontaneous or directed differentiation. Additionally, chromatin immunoprecipitation of GCM1 showed binding near key genes upregulated upon differentiation including the contact inhibition factor CDKN1C. Loss of GCM1 resulted in downregulation of CDKN1C and corresponding loss of contact inhibition, implicating GCM1 in regulation of this critical process.

Smoking in pregnancy is the leading avoidable cause of gestational morbidity and mortality, causally linked to fetal growth restriction (FGR). The placenta, functional interface between mother and fetus is essential for healthy fetal development. For the first time, we studied cell type-resolved smoking effects on placental development at high molecular resolution using single-nucleus RNA sequencing and deep visual proteomics of matched tissues. We validated our findings through an independent cohort and in-vitro cigarette smoke exposure to primary human trophoblast cells. Our results show placental macrophages (Hofbauer cells; HBC) and the syncytiotrophoblast (STB) barrier are most affected by smoking, with dysregulation of cell-cell adhesion, extracellular matrix organization, and stress phenotype. STBs show moderate compositional increases in smokers and in-silico trophoblast differentiation modelling indicates a preferential shift towards the STB lineage in this group. The trophoblast displays a large upregulation of pro-angiogenic effectors, increases in xenobiotic detoxification, reduced mitochondrial function, and vastly altered transmembrane transport. These molecular changes affect placental development with important consequences for fetal growth. We provide insight into placental dysfunction contributing to FGR early in pregnancy, before clinical symptoms appear. We anticipate this data to advance diagnostics and therapies to improve FGR outcomes. ### Competing Interest Statement The authors have declared no competing interest. Deutsche Forschungsgemeinschaft, HE6249/5-1, HE6249/7-1, HE6249/7-2, HE 6249/5-3 Volkswagen Stiftung, 9D289 German Centre for Cardiovascular Research, BER 1.1 VD Austrian Science Fund (FWF), 10.55776/P35118, 10.55776/I6907, 10.55776/PAT4258724 Federal Ministry of Education and Research (BMBF), 161L0222 European Union’s Horizon 2020, 101115681

AIMS:This cross-sectional study examined associations between self-reported taste perception changes and appetite-related outcomes in individuals with obesity treated with glucagon-like peptide-1 receptor agonist (GLP-1 RAS) or dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RAS in real-world conditions. MATERIALS AND METHODS:Four hundred and eleven adults on Wegovy® (n = 217), Ozempic® (n = 148) and Mounjaro® (n = 46) completed an online survey assessing sociodemographic, anthropometric and sensory changes and appetite-related outcomes. Multivariable logistic regression was used to assess associations between taste changes and satiety, appetite and craving. RESULTS:Participants (69.6% female; median age 39 [interquartile range, IQR 33-47]) had baseline body mass index (BMI) of 35.6 (Wegovy®), 34.7 (Ozempic®) and 36.2 kg/m2 (Mounjaro®). Adjusted models for baseline BMI, treatment duration, dose, age and sex showed significant reductions in BMI of 17.6% (95% CI: 15.7-19.5) for Wegovy®, 17.4% (15.0-19.8) for Ozempic® and 15.5% (8.8-22.2) for Mounjaro®. Reduced appetite was reported by 58.4% of participants (Wegovy®: 54.4%, Ozempic®: 62.1%, Mounjaro®: 56.5%) and increased satiety by 63.5% (Wegovy®: 66.8%, Ozempic®: 58.8%, Mounjaro®: 63.1%). Additionally, 21.3% reported increased sweet taste perception and 22.6% reported increased salty taste perception. Independent of the type of therapy, increased sweet taste perception was significantly associated with increased satiety (adjusted odds ratios [AOR] = 2.02; 95% CI: 1.15-4.57), decreased appetite (AOR = 1.67; 95% CI: 1.04-3.25) and decreased craving (AOR = 1.85; 95% CI: 1.05-3.29). Increased salty taste perception was associated with increased satiety (AOR = 2.17; 95% CI: 1.16-5.17; all p < 0.05). CONCLUSIONS:Self-reported changes in taste perception during GLP-1 or dual GIP/GLP-1 RAS therapy were associated with favourable appetite-related outcomes, suggesting a potential mechanism contributing to treatment response.

Introduction This review aimed to investigate the effects of chronic exercise on depression severity and various depressive symptoms in Randomized Controlled Trials (RCTs) including older adults with an average age of at least 60 years and a minimum level of mild depression. Thereby, the moderating effects of various intervention and individual characteristics were considered. Methods We searched Web of Science, Academic Search Complete, MEDLINE, CINAHL, APA Psycinfo, SPORTDiscuss, and Cochrane from inception until July 2023. Primary outcomes targeted changes in overall depression severity assessed with validated depression scales; secondary outcomes included changes in specific symptoms that are related to depression such as sleep quality, fatigue, anxiety, mood, apathy, weight changes, processing speed, and executive functions. These were measured from baseline until the end of the intervention. Meta-analysis was undertaken to synthesize the effects of chronic exercise on primary and secondary outcomes. The moderating effects of intervention and individual characteristics were investigated by subgroup-analyses and meta-regression. Publication bias was addressed through sensitivity analyses. The quality and certainty of the evidence were assessed using GRADE and RoB 2. Results The comprehensive search yielded 20,700 records, of which 145 peer-reviewed articles including 187 effect sizes met the inclusion criteria. We found that chronic exercise significantly improved overall depression severity (g = -0.68, p < .001, k = 187) as well as depressive symptoms related to anxiety (g = -0.56, p < .001, k = 24), BMI (g = -0.26, p = .005, k = 13), executive functions (g = -0.33, p = .004, k = 18), sleep (g = -0.47, p < .001, k = 14), and processing speed (g = -0.35, p = .015, k = 11). Regarding exercise characteristics, effects were particularly strong for interventions that included exergames, had a long duration, and involved high cognitive demand. Additionally, effects increased with advancing age and higher baseline depression severity. Egger’s test and an asymmetrical funnel plot suggest the presence of publication bias. Discussion/Conclusion This study is up to date the most extensive review on chronic exercise effects on depression in older adults. The results highlight the importance of individualizing exercise regimens to achieve optimal outcomes. The conclusions drawn may provide a foundation for developing evidence-based recommendations for exercise programs aimed at alleviating depression in older adults.

Insights into the molecular processes that drive early development of the human placenta is crucial for our understanding of pregnancy complications such as preeclampsia and fetal growth restriction, since defects in maturation of its epithelial cell, the trophoblast, have been detected in the severe forms of these diseases. However, key regulators specifying the differentiated trophoblast subtypes of the placenta are only slowly emerging. By using diverse trophoblast cell models, we herein show that the transcriptional coactivator of HIPPO signaling, TAZ, plays a pivotal role in the development of invasive extravillous trophoblasts (EVTs), cells that are essential for decidual vessel remodeling and adaption of maternal blood flow to the placenta. Ribonucleic acid sequencing (RNA-seq) or protein analyses upon TAZ gene silencing or CRISPR-Cas9-mediated knockout in differentiating trophoblast stem cells, organoids, primary EVTs, choriocarcinoma cells, or villous explant cultures unraveled that the coactivator promoted expression of genes associated with EVT identity, motility, and survival. Accordingly, depletion or chemical inhibition of TAZ, interacting with TEA domain family member 1 (TEAD1), impaired EVT differentiation, invasion, and migration and triggered apoptosis in the different trophoblast models. Notably, the coactivator also suppressed cell cycle genes and regulators of trophoblast self-renewal and prevented EVTs from cell fusion in organoids and primary cultures. Moreover, TAZ promoted human leukocyte antigen G (HLA-G) surface expression and increased NUAK1 kinase in EVTs thereby maintaining its own expression. In summary, the transcriptional coactivator TAZ plays a multifaceted role in the development of the EVT cell lineage by controlling different biological processes that initiate and preserve differentiation.

Developmental transitions are characterized by coordinated changes in lineage-specific gene expression programs and chromatin states. Yet how these shifts in cell fate occur during placental development remains largely unknown. Here, we have used human trophoblast stem cells (hTSCs), genetic depletion and small-molecule inhibition of the SWI/SNF remodelling complex activity to address its role during syncytiotrophoblast (ST) differentiation. We found that SWI/SNF inhibition has a massive impact on gene expression, chromatin accessibility and histone modifications, particularly H3K27ac, resulting in ST differentiation failure. We also observed cell cycle defects, indicating that SWI/SNF is required for hTSCs to exit the cell cycle, which is a prerequisite for ST commitment. In addition, based on motif analysis of SWI/SNF target regions, we genetically tested several early ST candidate transcription factors. While GCM1, CEBPB and TBX3 are vital for ST differentiation, only GCM1 is sufficient to induce ST fate. Together, our results demonstrate that SWI/SNF activity is essential for lineage specification during placental development.

During gestation, the human placenta ensures nutrition, gas exchange, and protection against pathogens for the growing fetus. As key component in placentation, extravillous trophoblasts (EVTs) arise from trophoblast (TB) progenitors through extensive proliferation at placental tip structures. A stepwise and tightly orchestrated differentiation process enables post-proliferative EVTs to invade maternal uterine layers, remodel the uterine vasculature, and modulate the maternal immune system to sustain pregnancy. Various signaling pathways are crucial in TB biology, including the MAPK, WNT, NOTCH, HIPPO, EGFR, and TGFβ cascades, which have been the subject of numerous comprehensive reviews. Recently developed TB model systems such as TB stem cells and TB organoids have significantly advanced placental research by enabling precise manipulation of signaling pathways and control over TB lineage determination and differentiation. Building on these advancements, this review specifically examines the activity and role of NOTCH, WNT, and TGFβ signaling in the sequential steps of EVT differentiation, integrating key insights gained from TB stem cell- and TB organoid-based studies.