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Worldwide trends to delay childbearing have increased parental ages at birth. Older parental age may harm offspring health, but mechanisms remain unclear. Alterations in offspring DNA methylation (DNAm) patterns could play a role as aging has been associated with methylation changes in gametes of older individuals. We meta-analyzed epigenome-wide associations of parental age with offspring blood DNAm of over 9500 newborns and 2000 children (5-10 years old) from the Pregnancy and Childhood Epigenetics consortium. In newborns, we identified 33 CpG sites in 13 loci with DNAm associated with maternal age (PFDR

Maternal educational attainment (MEA) shapes offspring health through multiple potential pathways. Differential DNA methylation may provide a mechanistic understanding of these long-term associations. We aimed to quantify the associations of MEA with offspring DNA methylation levels at birth, in childhood and in adolescence. Using 37 studies from high-income countries, we performed meta-analysis of epigenome-wide association studies (EWAS) to quantify the associations of completed years of MEA at the time of pregnancy with offspring DNA methylation levels at birth (n = 9 881), in childhood (n = 2 017), and adolescence (n = 2 740), adjusting for relevant covariates. MEA was found to be associated with DNA methylation at 473 cytosine-phosphate-guanine sites at birth, one in childhood, and four in adolescence. We observed enrichment for findings from previous EWAS on maternal folate, vitamin-B12 concentrations, maternal smoking, and pre-pregnancy BMI. The associations were directionally consistent with MEA being inversely associated with behaviours including smoking and BMI. Our findings form a bridge between socio-economic factors and biology and highlight potential pathways underlying effects of maternal education. The results broaden our understanding of bio-social associations linked to differential DNA methylation in multiple early stages of life. The data generated also offers an important resource to help a more precise understanding of the social determinants of health.

Higher birth order is associated with altered risk of many disease states. Changes in placentation and exposures to in utero growth factors with successive pregnancies may impact later life disease risk via persistent DNA methylation alterations. We investigated birth order with Illumina DNA methylation array data in each of 16 birth cohorts (8164 newborns) with European, African, and Latino ancestries from the Pregnancy and Childhood Epigenetics Consortium. Meta-analyzed data demonstrated systematic DNA methylation variation in 341 CpGs (FDR adjusted P

Summary: Background: Intrapartum antibiotics are used to prevent group B streptococcus disease in newborn infants. We hypothesised that intrapartum antibiotic exposure is associated with the occurrence of childhood infectious diseases because it influences the development of the gut microbiome. Methods: The cohort for this population-based study comprised vaginally delivered children born in Northern Finland in 2007–2018. We used structured electronic medical records linked to comprehensive national registers. Primary outcome was the number of infectious disease episodes leading to an emergency room visit, outpatient hospital visit, or hospitalisation from birth until five years of age. Findings: Analyses were performed on 9733 children (48.8% girls) exposed to intrapartum antibiotics and on 35,842 unexposed children (49.9% girls). Exposure to intrapartum antibiotics was associated with increased risk of any infectious disease episode at the ages 7−28 days (adjusted incidence rate ratio [aIRR] 1.30, 95% CI 1.10−1.54) and 1−2 years (aIRR 1.10, 95% CI 1.02–1.18). The occurrence of urinary tract infections was associated with the exposure to intrapartum antibiotics whereas the occurrence of severe infections caused by pathogens susceptible to penicillin was reversely associated with the exposure to intrapartum antibiotics. Interpretation: Maternal intrapartum antibiotics were associated with the occurrence of infectious diseases in the offspring. The observed associations appeared to depend on bacterial pathogens and their antimicrobial susceptibility to penicillin. Funding: Pediatric Research Foundation, Alma och K.A. Snellman Foundation, Orion Research Foundation, Päivikki and Sakari Sohlberg Foundation, Finnish Medical Foundation, Academy of Finland, Finland.

Abstract Hypoxia-inducible factors (HIF) 1 and 2 regulate similar but distinct sets of target genes. Although HIFs are best known for their roles in mediating the hypoxia response accumulating evidence suggests that under certain conditions HIFs, particularly HIF2, may function also under normoxic conditions. Here we report that HIF2α functions under normoxic conditions in kidney epithelial cells to regulate formation of adherens junctions. HIF2α expression was required to induce Dock4/Rac1/Pak1-signaling mediating stability and compaction of E-cadherin at nascent adherens junctions. Impaired adherens junction formation in HIF2α- or Dock4-deficient cells led to aberrant cyst morphogenesis in 3D kidney epithelial cell cultures. Taken together, we show that HIF2α functions in normoxia to regulate epithelial morphogenesis.

Abstract Currently, there are no accurate means to predict spontaneous preterm birth (SPTB). Recently, we observed low expression of alpha-1 antitrypsin (AAT) in SPTB placentas. Present aim was to compare the concentrations of maternal serum AAT in pregnancies with preterm and term deliveries. Serum C-reactive protein (CRP) was used as a reference inflammatory marker. Two populations were studied. The first population comprised women who eventually gave birth spontaneously preterm (SPTB group) or term (control group). The second population included pregnant women shortly before delivery and nonpregnant women. We observed that serum AAT levels were higher in the SPTB group than in the controls, and a similar difference was observed when serum CRP was considered in multivariable analysis. However, the overlap in the AAT concentrations was considerable. No statistical significance was observed in serum AAT levels between preterm and term pregnancies at delivery. However, AAT levels were higher at delivery compared to nonpregnant controls. We did not observe a strong correlation between serum AAT and CRP in early pregnancy samples and at labor. We propose that during early pregnancy, complicated by subsequent SPTB, modest elevation of serum AAT associates with SPTB.

Abstract Background The pathogenesis of inflammatory bowel disease (IBD) has not been fully elucidated. The aim of this study was to analyze the pregnancy period, perinatal period, and infancy period risk factors for IBD in a well-characterized birth cohort from Northern Finland. Methods The Northern Finland Birth Cohort 1966 (NFBC1966) population comprises mothers living in the two northernmost provinces of Finland, Oulu, and Lapland, with dates of delivery between Jan 1st and Dec 31st, 1966 (12 055 mothers, 12 058 live-born children, 96.3% of all births during 1966). IBD patients were identified using hospital registries (from 1966 to 2020) and Social Insurance Institution (SII) registry reimbursement data for IBD drugs (from 1978 to 2016). The data were analyzed by Fisher’s exact test and logistic regression. Results In total, 6972 individuals provided informed consent for the use of combined SII and hospital registry data. Of those, 154 (2.1%) had IBD (113 [1.6%] had ulcerative colitis (UC), and 41 (0.6%) had Crohn’s disease (CD)). According to multivariate analysis, maternal smoking > 10 cigarettes/day during pregnancy was associated with a nearly 6-fold increased risk of CD in the offspring (OR 5.78, 95% CI 1.70–17.3). Breastfeeding (OR = 0.18, 95% CI 0.08–0.44) and iron supplementation during the first year of life (OR = 0.43, 95% CI 0.21–0.89) were negatively associated with CD. Conclusions Smoking during pregnancy was associated with the risk of CD while Breastfeeding and oral iron supplementation at infancy were negatively associated with the risk of CD later in life.

Combined internal medicine and dermatology (med-derm) training programs were created to advance complex medical dermatology and inpatient dermatology care. A prior study demonstrated that compared to categorical dermatology residents, med-derm residents had less program satisfaction, yet indicated a stronger desire to pursue careers in academia. No follow-up data on practice patterns after training has been reported. We aimed to characterize differences in residency program satisfaction and practice patterns between physicians trained in categorical dermatology compared to med-derm residency programs. We surveyed physicians who graduated from combined med-derm programs along with their counterparts, from six institutions, that either currently or historically had a combined med-derm training, from 2008-2017. Fifty-five percent of med-derm and forty-one percent of categorical-trained physicians responded. The practice patterns between the two groups were similar. A quarter of med-derm physicians continued to provide general internal medicine services. Categorical trained physicians were significantly more satisfied with their training (P=0.03) and performed more excisions on the head/neck (P=0.02). The combined graduates had significantly greater confidence in multidisciplinary care (P=0.003), prescribed more biologic (P

Abstract Higher birth order is associated with altered risk of many disease states. Changes in placentation and exposures to in utero growth factors with successive pregnancies may impact later life disease risk via persistent DNA methylation alterations. We investigated birth order with Illumina DNA methylation array data in each of 16 birth cohorts (8164 newborns) with European, African, and Latino ancestries from the Pregnancy and Childhood Epigenetics Consortium. Meta-analyzed data demonstrated systematic DNA methylation variation in 341 CpGs (FDR adjusted P

The purpose of this study was to investigate teachers' ethical sensitivity in Finland (N = 255) and Estonia (N = 412). The survey included the quantitative "Ethical Sensitivity Scale Questionnaire" and a qualitative open-ended question about successful teaching. In order to capture its essential characteristics, ethical sensitivity was examined using a four-factor structure. Triangulated data indicated that "Caring by connecting to others" was the most essential dimension of ethical sensitivity among both Finnish and Estonian teachers. By contrast, "Reading ethical issues" was the lowest rated and least mentioned dimension of ethical sensitivity. Approximately 30% of teachers from both countries did not perceive ethical sensitivity to be part of successful teaching. The results indicate the need for moral education to help teachers gain a more holistic understanding of the moral nature of teaching and recognize and visualize solutions for moral dilemmas in school communities.

Abstract Retirement from elite sport represents a major life transition for athletes and requires them to redefine their central life projects, identities, and perhaps even sources of meaning in life. Although an extensive body of literature has identified risk and protective factors in career termination, little is known about the more subjective processes and individual pathways of athletes as they establish their new relationship with work-life and sport. The planned longitudinal mixed methods study follows Swiss elite athletes’ transition with a focus on understanding (1) the relationship between psychological resources, life situations at the end of the sports career, and the retirement process; (2) how athletes’ post-retirement vocational careers interact with their subjective careers and sense of meaningful work; (3) how athletes reconstruct their identities and relationship with sport over time; and (4) how gender shapes athletes’ pathways and reorientation of their life design. Using a person-oriented approach combined with narrative inquiry, we expect to identify specific types and stories which demonstrate individual differences in career and personal development throughout the transitional period, an understanding of which can be targeted towards support programmes for retiring elite athletes. As the study centralises dimensions of positive psychological functioning (meaning and purpose in life/sport/work, resilience, life satisfaction), it complements previous studies focused on psychological distress and provides much needed knowledge that can be used to foster well-being in athletic retirement. Collaborating with the Swiss Olympic Association helps to ensure that the research findings will be disseminated to relevant end-users and used towards developing socially sustainable elite sport for the future generations.

The novel contribution of this research is decentralised IOTA-based concepts of digital trust for securing remote driving in an urban environment. The conceptual solutions are studied and described, and respective experimental solutions are developed relying on digital identities, public key cryptography with a decentralised approach using decentralised identifiers (DIDs) and verifiable credentials (VCs), and an IOTA-based distributed ledger. The provided digital trust solutions were validated by executing them according to the remote driving scenario but with a simulated vehicle and simulated remote driving system. The hybrid simulation mainly focused on the validation of functional, causal temporal correctness, feasibility, and capabilities of the provided solutions. The evaluations indicate that the concepts of digital trust fulfil the purpose and contribute towards making remote driving more trustable. A supervisory stakeholder was used as a verifier, requiring a set of example verifiable credentials from the vehicle and the remote driver, and accepting them to the security control channel. The separation of control and data planes from each other was found to be a good solution because the delays caused by required security control can be limited to the initiation of the remote driving session without causing additional delays in the actual real-time remote driving control data flow. The application of the IOTA Tangle as the verifiable data registry was found to be sufficient for security control purposes. During the evaluations, the need for further studies related to scalability, application of wallets, dynamic trust situations, time-sensitive behaviour, and autonomous operations, as well as smart contract(s) between multiple stakeholders, were detected. As the next step of this research, the provided digital trust solutions will be integrated with a vehicle, remote driving system and traffic infrastructure for evaluation of the performance, reliability, scalability, and flexibility in real-world experiments of remote driving of an electric bus in an urban environment.

Remote operations have been greatly enhanced by advancements in technology, enabling remote control of machinery in hazardous environments. However, it is still a challenge to design remote control interfaces and provide feedback in a way that would enhance situational awareness without negatively affecting cognitive load. This study investigates how different audio feedback designs can support remote boom operation and, additionally, explores the potential impact of gamification elements on operator performance and motivation. Due to COVID-19 restrictions, this study was conducted remotely with 16 participants using a simulated environment featuring a virtual excavator. Participants performed digging tasks using two audio feedback designs: frequency-modulated beeping and realistic spatialized steam sounds. The findings indicate that both audio designs are beneficial for remote boom operations: the beeping sound was perceived as more comfortable and efficient in determining the proximity of a hidden object and helped in avoiding collisions, whereas spatial sounds enhanced the sense of presence. Therefore, we suggest combining both audio designs for optimal performance and emphasize the importance of customizable feedback in remote operations. This study also revealed that gamification elements could both positively and negatively affect performance and motivation, highlighting the need for careful design tailored to specific task requirements.

Abstract Background Aneurysmal subarachnoid hemorrhage (aSAH) is a neurological emergency, affecting a younger population than individuals experiencing an ischemic stroke; aSAH is associated with a high risk of mortality and permanent disability. The noble gas xenon has been shown to possess neuroprotective properties as demonstrated in numerous preclinical animal studies. In addition, a recent study demonstrated that xenon could attenuate a white matter injury after out-of-hospital cardiac arrest. Methods The study is a prospective, multicenter phase II clinical drug trial. The study design is a single-blind, prospective superiority randomized two-armed parallel follow-up study. The primary objective of the study is to explore the potential neuroprotective effects of inhaled xenon, when administered within 6 h after the onset of symptoms of aSAH. The primary endpoint is the extent of the global white matter injury assessed with magnetic resonance diffusion tensor imaging of the brain. Discussion Despite improvements in medical technology and advancements in medical science, aSAH mortality and disability rates have remained nearly unchanged for the past 10 years. Therefore, new neuroprotective strategies to attenuate the early and delayed brain injuries after aSAH are needed to reduce morbidity and mortality. Trial registration ClinicalTrials.gov NCT04696523. Registered on 6 January 2021. EudraCT, EudraCT Number: 2019-001542-17. Registered on 8 July 2020.

Introduction Athletes’ heart-felt stories about their experiences in elite sport almost naturally evoke the notion of meaning. However, although various scholars and practitioners have suggested the concept of meaning to the sport psychology audience in the past two decades (e.g., Beckmann, 2023; Ravizza, 2002; Ronkainen & Nesti, 2020), its study in this discipline is still in the early stages compared to established psychological scholarship on the topic. To promote meaning as a complementary lens for research and applied work in sport psychology, the presentation aims to introduce the concept informed by psychological inquiry, and to synthesize and critically comment on the extant scholarship. For this, the wider meaning in life literature will be drawn on to give an overview of components, sources, pathways, and qualities of meaning and set it apart from the related concept of purpose. Methods A narrative review of 15 studies on meaning (n = 10) and purpose (n = 5) from elite sport contexts was conducted. Results The scholarship on meaning and purpose in elite sport revealed itself diverse in terms of employed study designs (quantitative, qualitative), methodologies and theoretical frameworks (e.g., narrative inquiry, phenomenology), conceptualizations of meaning and purpose (e.g., existential meaning, purpose in coaching), interpretations of meaning (intrapsychic or relational), and topics researched in relation to it (e.g., forced migration, injury experiences). To date the literature base on meaning and purpose in elite sport is characterized by fragmentation and largely imprecise use of the concept. Discussion/Conclusion To assist future empirical research and increase conceptual clarity of meaning in elite sport, sport psychology should integrate knowledge from its parent discipline psychology. Additionally, to make the somewhat abstract notion of meaning tangible for sport practitioners, more applied questions must be addressed. Through this, meaning could offer a truly holistic approach to well-being and mental health research and practice in sport. Importantly, “working” with meaning requires personal positioning, since conceiving of meaning as performance enhancement tool or as existential concern has major implications for how it is investigated and for how or whether it should be increased. References Beckmann, J. (2023). Meaning and meaninglessness in elite sport. In I. Nixdorf, R. Nixdorf, J. Beckmann, S. Martin, & T. Macintyre (Eds.), Routledge Handbook of Mental Health in Elite Sport (pp. 31–44). Routledge. https://doi.org/10.4324/9781003099345-5 Ravizza, K. (2002). A philosophical construct: A framework for performance enhancement. International Journal of Sport Psychology, 33, 4–18. Ronkainen, N. J. & Nesti, M. S. (2019). Meaning and Spirituality in Sport and Exercise: Psychological Perspectives. Routledge. https://doi.org/10.4324/9781315102412

A characterising trait of qualitative research, as opposed to quantitative research, is its assumed focus on meaning. For example, Smith and Sparkes (2016, p. 2) suggested that “To interpret phenomena in terms of the meanings people bring to them, qualitative researchers draw on a variety of empirical materials”. Although there might be an intuitive understanding of what “meaning” means, different traditions of qualitative research have unique ways of conceptualising where meaning is located and how it might best be studied. In this presentation, we will explore three qualitative traditions – phenomenology, narrative inquiry and cultural analysis – to explicate these different assumptions and how they influence the qualitative research process. Firstly, we will focus on phenomenological approaches to qualitative research which often emphasise the lived, pre-verbal experience of meaning before it is crystallised into words. From this perspective, the challenge for the qualitative research is to help the participants to explicate meanings of their experience through careful questioning. Secondly, we explore narrative approaches that consider meaning as created through storytelling and co-constructed with the researcher with particular audiences in mind. From this perspective, meaning is personal, but constructed from the cultural building blocks of example stories that are available to the storyteller. Finally, in cultural analysis, the focus is not on personal meaning, but rather the culturally shared webs of significance that make meaningful actions possible for cultural insiders. We conclude that explicating the types of assumptions that researchers draw on in the study of meaning can enhance the quality of qualitative research, and that the diverse perspectives often lead to complementary, enriching understandings of meaning in the world of sport and physical culture. References Smith, B., & Sparkes, A. C. (Eds.). (2016). Routledge Handbook of Qualitative Research in Sport and Exercise. Routledge.

Introduction The concept of meaning in life has gained significant attention in psychology research in recent years due to its correlational relationship with physical and mental well-being (i.e., objective and subjective health measures, e.g., Steger, 2012). While recent attention has been directed toward this concept in sport psychology using qualitative research methods (e.g., Ronkainen et al., 2015), quantitative investigations into the specific sources of meaning engaged by athletes are notably scarce. This study (1) compares athletes with the general population and (2) employs a person-oriented approach to identify distinct profiles of athletes’ meaning in life and the sources they predominantly tap into. Methods A sample of 589 elite athletes from Switzerland (50.9% women, 49.1% men; Mage = 24.86 years, SD = 5.09) participated in this study. Utilizing the Meaning and Purpose Scales (MAPS; Schnell & Danbolt, 2023), participants also provided contextual information about their life situations. The athletes were compared with the general population using t-tests. To identify profiles within the athlete population, we employed a latent profile analysis. Results Compared to the general population, athletes exhibit heightened meaningfulness and lower crisis of meaning and prioritise different sources of meaning. Athletes were higher in Growth and Community and lower in Faith, Sustainability and Security. The analysis yielded a three-profile solution based on theoretical considerations and statistical criteria: (1) athletes with below-average meaning in life and sources (n = 127), (2) athletes with above-average meaning in life and faith (n = 109), (3) athletes with above-average meaning in life with balanced sources (n = 353). Athletes in profiles 2 and 3 were characterized by elevated levels of meaningfulness and sources of meaning, and demonstrated greater life satisfaction and self-esteem, relative to the profile with below-average meaning in life and sources. Discussion/Conclusion The identified relationships with key mental health constructs align with qualitative findings emphasizing the centrality of meaningfulness in athletes’ lives. On a nomothetic level, elite athletes indicate a high degree of meaningfulness (compared to the population), however, there is a high degree of heterogeneity within the sample, which is why group-specific analysis (i.e., LPA) could help understanding meaning and its sources in elite athletes. In the future this approach could be useful to tailor programs aimed at cultivating meaning in life of elite athletes. References Ronkainen, N. J., Tikkanen, O., Littlewood, M., & Nesti, M. S. (2015). An existential perspective on meaning, spirituality and authenticity in athletic careers. Qualitative Research in Sport, Exercise and Health, 7(2), 253–270. https://doi.org/10.1080/2159676X.2014.926970 Schnell, T., & Danbolt, L. J. (2023). The Meaning and Purpose Scales (MAPS): Development and multi-study validation of short measures of meaningfulness, crisis of meaning, and sources of purpose. BMC Psychology, 11(1), Article 304. https://doi.org/10.1186/s40359-023-01319-8 Steger, M. F. (2012). Experiencing meaning in life—Optimal functioning at the nexus of well-being, psychopathology, and spirituality. In P. T. P. Wong (Ed.), The Human Quest for Meaning: Theories, Research, and Applications (2nd ed., pp. 165–184). Routledge.

[This corrects the article DOI: 10.1371/journal.pone.0279443.].

ABSTRACTFecal microbiota transplantation (FMT) is used routinely to treat recurrent Clostridioides difficile infection (rCDI) and investigated as a treatment for numerous conditions associated with gut microbiota alterations. Metagenomic analyses have indicated that recipient colonization by donor bacteria may be associated with favorable clinical outcomes. Bifidobacteria are abundant gut commensals associated with health. We have previously demonstrated that Bifidobacterium strains transferred in FMT can colonize recipients in long term, at least for a year, and recovered such strains by cultivation. This study addressed in vitro adhesion and pilus gene expression of long-term colonizing Bifidobacterium strains from FMT donors as well as in vivo colonization and capability to ameliorate antibiotic-induced microbiota disturbance. RNA-Seq differential gene expression analysis showed that the strongly adherent B. longum strains DY_pv11 and DX_pv23 expressed tight adherence and sortase-dependent pilus genes, respectively. Two B. longum strains, adherent DX_pv23 and poorly adhering DX_pv18, were selected to address in vivo colonization and efficacy to restore antibiotic-disturbed microbiota in C57BL/6 murine model. DX_pv23 colonized mice transiently with a rate comparable to that of the B. animalis BB-12 used as a reference. Although long-term colonization was not observed with any of the three strains, 16S rRNA gene profiling revealed that oral administration of DX_pv23 enhanced the recovery of antibiotic-disturbed microbiota to the original configuration significantly better than the other strains. The findings suggest that selected strains from FMT donors, such as DX_pv23 in this study, may have therapeutic potential by in vitro expression of colonization factors and boosting endogenous gut microbiota.