Abstract Machine-learned interatomic potentials enable large systems to be simulated for long time scales at near ab-initio accuracy. This accuracy is achieved by fitting extremely flexible model architectures to high quality reference data. In practice, this flexibility can cause unwanted behavior such as jagged predicted potential energy surfaces and generally poor out-of-distribution behavior. We investigate a general strategy for incorporating prior beliefs on the regularity of the target energy into linear ACE models and explore to what extent this approach improves the quality of the fitted models. Our main focus is an over-regularisation that replicates the Gaussian broadening used in SOAP descriptors within the ACE framework. Numerical tests indicate that the exact form of the prior is non-critical but that including such a prior leads to significant improvement in test errors, consistent repulsion at close-approach, eliminates spurious false minima in the potential energy and enhances stability during molecular dynamics simulations.

Genetic factors may contribute to the heritability and susceptibility of recurrent aphthous ulcers (RAU). This study evaluated the heritability of RAU in the TwinsUK registry. Data from 890 twin pairs (319 monozygotic [MZ] and 571 dizygotic [DZ]) were used to estimate the prevalence of RAU in the previous year and 8 subphenotypes. A classical twin design was used to partition the variance in RAU presentation into components attributable to additive genetic (A), common/shared environmental (C), dominance genetic (D), and unique/nonshared environmental (E) effects. A multilevel ACE/ADE model with random effects at both the individual and twin-pair levels was fitted to the prevalence of RAU and each subphenotype separately. RAU prevalence in the previous year was 9.3%, with MZ and DZ twin correlations of 0.59 (95% confidence interval [CI]: 0.37, 0.82) and 0.30 (0.09, 0.82), respectively. The ACE model estimated the heritability of RAU prevalence in the previous year at 55.69% (34.43% to 76.95%). Using stricter RAU criteria yielded similar heritability estimates (58.82% [36.51, 81.14]), reinforcing the robustness of the findings. Among subphenotypes, frequency of episodes (53.61% [33.09, 74.13]) and time between occurrences (53.08% [30.96, 75.19]) showed the largest genetic contribution, while ulcer size had the lowest genetic contribution (40.55% [14.76, 66.33]). Heritability estimates for the number of RAU (50.32%, 95% CI: 25.99, 74.65), healing time (49.24% [27.46, 71.03]), and location in soft tissues (42.85% [12.91, 72.78]) and hard tissues (40.70% [12.43, 68.97]) fell between those values. The findings indicate a genetic contribution to RAU susceptibility, with heritability estimates differing across various phenotypic presentations of the condition.

Perinatal factors affect gut microbiota and infant health, but the combined impacts of preterm birth and chorionicity on gut microbiota, metabolism, and physical/neurobehavioral development in twins remain unclear. A total of 143 twin families (12-month-old infants) were enrolled and divided into four groups by gestational age and chorionicity (dichorionic-diamniotic full-term/preterm, monochorionic-diamniotic full-term/preterm). Gut microbiota diversity and fecal metabolism were analyzed via 16S rRNA sequencing and untargeted metabolomics. Wilcoxon's rank-sum tests, generalized estimating equations, and twin-based ACE models were used for alpha diversity comparison, differential microbiota identification, and genetic/environmental contribution evaluation, respectively, with confounder adjustment in development association analysis. We identified 10 group-specific gut microbiota genera and 394 differential metabolites. Fifty-two microbiota taxa showed genetic variance, but none overlapped with group-specified taxa. Six genera and 18 metabolites correlated with twins' physical/neurobehavioral development. Pathway analysis highlighted three key metabolites: Morphine (isoquinoline alkaloid biosynthesis, drug metabolism, neuroactive ligand-receptor interaction), Nicotinuric acid (nicotinate/nicotinamide metabolism), and Catechin (flavonoid/phenylpropanoid biosynthesis). Preterm birth is linked to gut microbiota dysbiosis and metabolic perturbations, which may affect twin development. Notably, preterm birth exerts a stronger effect than genetic factors in shaping the gut microbiota of 12-month-old twins.

Introduction: Severe intraventricular hemorrhage (sIVH) remains a significant complication for very preterm infants (VPIs). This study aimed to assess heritable and environmental contributions to sIVH. Methods: A total of 2,074 twin pairs born at gestational age <32 weeks with known sIVH status were identified. Three statistical methods were applied, including the Pearson χ2 test, intra-class correlation (ICC), and ACE modeling. Results: Both Pearson’s χ2 test (p = 0.224) and ICC analysis (p = 0.534) revealed no significant difference after comparing neither, one, or both of the monochorionic and dichorionic twin pairs who developed sIVH. ACE modeling revealed no contribution of heritability to sIVH risk, while the common environmental impacts on sIVH development were 27.9% (95% CI [23.9%, 31.9%]) and 72.1% (95% CI [68.1%, 76.1%]), respectively. Assisted conception (aOR 1.45, 95% CI [1.06, 1.97]), inotropes (<3 days) (aOR 1.71, 95% CI [1.22, 2.39]), invasive mechanical ventilation (<3 days) (aOR 2.38, 95% CI [1.56, 3.64]), and sedations (<7 days) (aOR 2.25, 95% CI [1.55, 2.06]) had contribution to sIVH, while larger gestational age (aOR 0.77 [0.71, 0.85]) and early surfactant administration (≤2 h) (aOR 0.58, 95% CI [0.42, 0.79]) prevented VPIs from sIVH. Conclusions: We recognized that environmental factors instead of heritability may play major contribution to the development of sIVH. Quality improvement studies focusing on the potential environmental factors to decrease the incidence of sIVH are warranted.

Levels of neonatal Acute Phase Proteins (APPs) have been associated with autism and schizophrenia. The relative contributions of genetic and environmental factors to variation in APP levels in the neonatal period are not known. Therefore, we used one of the largest twin samples to date to map the proportions of heritable and non-heritable factors to variations in APPs measured shortly after birth. Moreover, we investigated if any association existed between neonatal APP levels and autism, among monozygotic and dizygotic twins discordant for autism.Twins were identified and enrolled from registers and a clinical twin study of autism in Sweden. The distributions of APPs measured in dried blood spots taken a few days after birth as part of a national screening program were standardized to reduce any analytical artifacts. The additive genetic (A), common (C) and unique (E) environment components were estimated, using the ACE model, on a sample of 92 twin pairs. We included 61 autism discordant twin pairs for estimating the association between the APPs and autism, using both non-fixed (between) and fixed (within) effects regression models.For the ACE models, variations in α-2 macroglobulin, C-reactive protein, ferritin, fibrinogen, haptoglobin, serum amyloid A and serum amyloid P were all largely explained by additive genetic factors (70–90 %). Variation in tissue plasminogen activator and procalcitonin were predominantly explained by common environmental factors (60–70 %) with a negligible contribution by genetic factors. Variations in levels of tissue plasminogen activator and procalcitonin in the neonatal period appear to be mainly explained by pregnancy and birth related factors. Variations in levels of other investigated acute phase proteins were largely explained by additive genetic factors. None of the APPs exhibited any significant association with autism in discordant mono- or dizygotic twin pairs. Our findings highlight the importance of considering potential familial confounding in future studies of association between any APP and autism.

Human creativity is broadly defined as the capacity to generate adaptive and useful ideas.From an evolutionary perspective, creativity has been theorized to function as a mental ornament, a trait shaped by sexual selection to signal genetic quality (e.g., intelligence, behavioral flexibility) in mate choice and competition.Indeed, artistic behavior is strategically displayed in courtship.Thus, if artistic creativity serves as a fitness indicator, we expect (1) significant heritability, reflecting genetic variance for sexual selection to act upon, and (2) predominant non-shared environmental influences, as ornament expression often depends on social context.We tested these predictions in a sample of 84 pairs of Brazilian twins (71 monozygotic and 13 dizygotic).Using ACE modeling, we found that 15.8% of the variance in artistic creativity was attributable to additive genetic effects, <1% to shared environmental influences, and 84.2% to non-shared environmental factors.The results are consistent with the hypothesis that artistic creativity represents a mental ornament shaped by sexual selection and modulated by contextual environmental factors.The dominance of non-shared environmental influences suggests that individual differences in artistic creativity arise largely from idiosyncratic experiences (e.g., individual opportunities, mentors, or peer feedback) rather than shared cultural or familial contexts.This aligns with sexual selection theory if artistic display is tailored to specific social niches (e.g., adapting creative output to attract particular mates or gain status within a group).Future research should include larger samples and diverse creativity measures to test the evidence base of the mental ornament theory.

IntroductionAdverse childhood experiences (ACEs) are linked to poor outcomes in adulthood, but extrafamilial violence (EFV), such as bullying, community and collective violence, remains relatively under-researched. This study aimed to estimate the prevalence of both the commonly measured ACEs and EFV in Northern Ireland (NI), a postconflict region and assess the association with physical and psychological outcomes.MethodsA representative sample of 1200 adults completed a standardised assessment of childhood adversity (WHO Adverse Childhood Experiences International Questionnaire) covering 13 ACEs. Logistic regressions assessed the association between high ACE exposure (4+vs 0) and adult mental and physical health, health behaviours and service use, adjusting for age, gender and deprivation. Adjusted ORs (AORs), population attributable fractions and additional variance explained were reported.ResultsWhen EFVs were included alongside commonly measured ACEs, 60.0% (n=719) of the NI sample reported at least one ACE and 17.6% (n=212) reported four or more. EFVs were independently associated with poor mental health outcomes, including post-traumatic stress disorder (PTSD)/complex PTSD (CPTSD) (AOR=14.8, 95% CI (6.5, 33.8)) and anxiety (AOR=7.5, 95% CI 4.9 to 11.4), contributing up to 18.3% (n=41) of anxiety cases. EFVs were also linked to substance use, chronic pain and frequent health service contact. While the most commonly measured ACEs predicted involvement in the justice system, EFVs significantly improved model fit for most health outcomes.ConclusionsEFV is a common and impactful form of childhood adversity. Including EFVs in ACE models improves predictive accuracy, particularly for mental health. ACE research and policy frameworks should be broadened to reflect the added burden of EFV.

Abstract The phenomenon of internationalization of higher education is widely recognized as a pressing need in a globalized context. Consequently, numerous countries and institutions have dedicated themselves to establishing internationalization policies, given their strategic relevance in promoting knowledge. This study investigated the perspectives of institutional actors in relation to the internationalization process of higher education institutions in Rio Grande do Sul. Using a predominantly quantitative approach, 57 respondents participated in this study, which, in addition to utilizing questionnaires with closed and open questions for data collection, analyzed the content of official strategic documents of the institutions investigated, based on the six axes of the ACE Model of Comprehensive Internationalization. In the Brazilian scenario, the internationalization of higher education still lacks clear guidelines from the public authorities to guide its implementation in institutions. Although institutional actors recognize the importance of internationalization, there is a perception that it is still conducted in isolation by a restricted group of individuals, predominantly associated with postgraduate studies. Several barriers are identified for comprehensive internationalization, including the lack of continuing training programs for teachers, challenges in implementing evaluation processes, the scarcity of internationalized courses in disciplines, and the absence of metrics that allow evaluation of learning outcomes.

Investigate genetic and environmental influences on refractive errors in monozygotic (MZ) and dizygotic (DZ) twin pairs. We assessed foveal and peripheral refractions in 54 MZ and 46 DZ twins, capturing three scans across the retina. The study focused on spherical equivalent (M) at the fovea (MLOS) and changes in midperipheral (δMmid-periphery), and peripheral (δMperiphery) defocus, along with nasal-temporal asymmetry (root mean squared error [RMSEASY]) and image shell contour (RMSEAVG). Genetic and environmental contributions were analyzed using structural equation models. No significant differences were observed between MZ and DZ twins for the examined variables. Intraclass correlations (ICC) indicated an important difference in genetic influence between MLOS, with the MZ twin pairs showing a higher correlation (0.83) than DZ (0.69) pairs, and δMperiphery, because the ICC for the MZ doubled (0.87) that of the DZ (0.42) pairs. Heritability estimates from the ACE model confirmed the large difference on genetic factors' influence on the variance for MLOS (0.13) and δMperiphery (0.77) change in refractive error. RMSEASY and RMSEAVG metrics showed significant genetic impact, particularly pronounced in the peripheral measurements, revealing high genetic control. The study delineates a marked environmental impact on central refractive errors, whereas genetic factors had a more significant influence on peripheral refractive variance and retinal image traits. Findings of the ACE model highlight the intricate genetic and environmental interplay in refractive error development, with a notable genetic dominance in peripheral vision characteristics. This suggests potential genetic targets for interventions in myopia management and emphasizes the need for personalized approaches based on genetic predispositions. Understanding the impact of genetics and environment on peripheral refraction is essential for deepening our fundamental knowledge of myopia and guiding the development of advanced myopia control strategies.

The interplay of genetic and environmental factors on the morphology of the limbic cortex and hippocampal subfields: Insights from an MRI twin study

Voice production can be influenced by interindividual variations related to genetic, physiological, behavioral, and several environmental factors. Here we examined the effect of zygosity on speaking fundamental frequency (F0) statistical descriptors. Our aims were: (1) to determine whether the genetic similarity between monozygotic (MZ) and dizygotic (DZ) twins affects F0 characteristics, and (2) to quantify the contribution of genetic factors to these characteristics. The study involved 79 same-sex twin pairs of Brazilian Portuguese speakers, comprising 65 MZ and 14 DZ twins, aged 18 to 66 years (31.7 ± 11.6 years), with 21 male and 58 female pairs. Participants were recorded while uttering a greeting phrase and the Brazilian Portuguese version of the 'Happy Birthday to You' song. Speech segments were analyzed using Praat free software, and F0 measures were automatically extracted in both Hertz and semitone scales. Statistical descriptors, including centrality, dispersion, and extreme values of F0 were examined, and the ACE model (i.e., total genetic effects, A; shared environmental influences, C; and nonshared environmental influences, E) was employed to estimate the additive effect;ts of monozygosity. As anticipated, we observed a zygosity effect on several F0 parameters, with more similarity between MZ twins compared to DZ twins. We discuss the genetic influences on F0 parameters and the absence of a monozygosity effect in two of them. Additionally, we briefly address potential biases associated with the selected measurement scale for statistical modeling. Finally, we explore the influence of genetic factors on F0 patterns, as well as environmental, life history and linguistic factors, particularly concerning F0 variation in speech.

Transgenerational impact of maternal adverse childhood experiences on children's mental health among families experiencing homelessness

Antimicrobial photodynamic therapy (aPDT) is a promising approach to combat antibiotic resistance in endodontic infections. It eliminates residual bacteria from the root canal space and reduces the need for antibiotics. To enhance its effectiveness, an in silico and in vitro study was performed to investigate the potential of targeted aPDT using natural photosensitizers, Kojic acid and Parietin. This approach aims to inhibit the biofilm formation of Enterococcus faecalis, a frequent cause of endodontic infections, by targeting the Ace and Esp proteins. After determining the physicochemical characteristics of Ace and Esp proteins and model quality assessment, the molecular dynamic simulation was performed to recognize the structural variations. The stability and physical movement of the protein-ligand complexes were evaluated. In silico molecular docking was conducted, followed by ADME/Tox profiling, pharmacokinetics characteristics, and assessment of drug-likeness properties of the natural photosensitizers. The study also investigated the changes in the expression of genes (esp and ace) involved in E. faecalis biofilm formation. The results showed that both Kojic acid and Parietin complied with Lipinski’s rule of five and exhibited drug-like properties. In silico analysis indicated stable complexes between Ace and Esp proteins and the natural photosensitizers. The molecular docking studies demonstrated good binding affinity. Additionally, the expression of the ace and esp genes was significantly downregulated in aPDT using Kojic acid and Parietin with blue light compared to the control group. This investigation concluded that Kojic acid and Parietin with drug-likeness could efficiently interact with Ace and Esp proteins with a strong binding affinity. Hence, natural photosensitizers-mediated aPDT can be considered a promising adjunctive treatment against endodontic infections.

Leveraging protein language model embeddings and logistic regression for efficient and accurate in-silico acidophilic proteins classification

Disease-discordant twins are excellent subjects for matched case-control studies as they allow for the control of confounding factors such as age, gender, genetic background, and intrauterine and early environment factors. Study design: A cross-sectional study. Past medical history documentation and physical examination were conducted for all participants. Fasting venous blood samples were taken to measure fasting blood glucose (FBG) and lipid levels. The ACE model, a structural equation model, was used to assess heritability. This study included 710 twin pairs (210 monozygotic and 500 dizygotic) ranging in age from 2 to 52 years (mean age: 11.67±10.71 years). The study was conducted using participants from the Isfahan Twin Registry (ITR) in 2017. Results showed that in early childhood (2-6 years), height, weight, and body mass index (BMI) were influenced by shared environmental factors (76%, 75%, and 73%, respectively). In late childhood (7-12 years), hip circumference, waist circumference (WC), and low-density lipoprotein (LDL) cholesterol were found to be highly heritable (90%, 76%, and 64%, respectively). In adolescents, height (94%), neck circumference (85%), LDL-cholesterol (81%), WC (70%), triglycerides (69%), weight (68%), and BMI (65%) were all found to be highly or moderately heritable. In adult twins, arm circumference (97%), weight (86%), BMI (82%), and neck circumference (81%) were highly heritable. This study demonstrates that both genetic and environmental factors play a role in influencing individuals at different stages of their lives. Notably, while certain traits such as obesity have a high heritability during childhood, their heritability tends to decrease as individuals transition into adulthood.

Reward-based eating drives are putative mechanisms of uncontrolled eating implicated in obesity and disordered eating (e.g., binge eating). Uncovering the genetic and environmental contributions to reward-related eating, and their genetic correlation with BMI, could shed light on key mechanisms underlying eating and weight-related disorders. We conducted a classical twin study to examine how much variance in uncontrolled eating phenotypes and body mass index (BMI) was explained by genetic factors, and the extent that these phenotypes shared common genetic factors. 353 monozygotic twins and 128 dizygotic twins completed the Reward-based Eating Drive 13 scale, which measures three distinct uncontrolled eating phenotypes (loss of control over eating, preoccupation with thoughts about food, and lack of satiety), and a demographic questionnaire which included height and weight for BMI calculation. We estimated additive genetic (A), common environmental (C), and unique environmental (E) factors for each phenotype, as well as their genetic correlations, with a multivariate ACE model. A common pathway model also estimated whether genetic variance in the uncontrolled eating phenotypes was better explained by a common latent uncontrolled eating factor. There were moderate genetic correlations between uncontrolled eating phenotypes and BMI (.26-.41). Variance from the uncontrolled eating phenotypes was also best explained by a common latent uncontrolled eating factor that was explained by additive genetic factors (52%). These results suggest that uncontrolled eating phenotypes are heritable traits that also share genetic variance with BMI. This has implications for understanding the cognitive mechanisms that underpin obesity and disordered eating. Our study clarifies the degree to which uncontrolled eating phenotypes and BMI are influenced by shared genetics and shows that vulnerability to uncontrolled eating traits is impacted by common genetic factors.

The heritability of ability tilts

The current study explored the impact of genetic relatedness differences (ΔH) and sample size on the performance of nonclassical ACE models, with a focus on same-sex and opposite-sex twin groups. The ACE model is a statistical model that posits that additive genetic factors (A), common environmental factors (C), and specific (or nonshared) environmental factors plus measurement error (E) account for individual differences in a phenotype. By extending Visscher's (2004) least squares paradigm and conducting simulations, we illustrated how genetic relatedness of same-sex twins (HSS) influences the statistical power of additive genetic estimates (A), AIC-based model performance, and the frequency of negative estimates. We found that larger HSS and increased sample sizes were positively associated with increased power to detect additive genetic components and improved model performance, and reduction of negative estimates. We also found that the common solution of fixing the common environment correlation for sex-limited effects to .95 caused slightly worse model performance under most circumstances. Further, negative estimates were shown to be possible and were not always indicative of a failed model, but rather, they sometimes pointed to low power or model misspecification. Researchers using kin pairs with ΔH less than .5 should carefully consider performance implications and conduct comprehensive power analyses. Our findings provide valuable insights and practical guidelines for those working with nontwin kin pairs or situations where zygosity is unavailable, as well as areas for future research.

Astigmatism and myopia are two common ocular refractive errors that can impact daily life, including learning and productivity. Current knowledge suggests that the etiology of these conditions is the result of a complex interplay between genetic and environmental factors. Studies in populations of European ancestry have demonstrated a higher concordance of refractive errors in monozygotic (MZ) twins compared to dizygotic (DZ) twins. However, there is a lack of studies on genetically informative samples of multi-ethnic ancestry. This study aimed to estimate the genetic contribution to astigmatism and myopia in the Mexican population. A sample of 1399 families, including 243 twin pairs and 1156 single twins, completed a medical questionnaire about their own and their co-twin's diagnosis of astigmatism and myopia. Concordance rates for astigmatism and myopia were estimated, and heritability and genetic correlations were determined using a bivariate ACE Cholesky decomposition method, decomposed into A (additive genetic), C (shared environmental) and E (unique environmental) components. The results showed a higher concordance rate for astigmatism and myopia for MZ twins (.74 and .74, respectively) than for DZ twins (.50 and .55). The AE model, instead of the ACE model, best fitted the data. Based on this, heritability estimates were .81 for astigmatism and .81 for myopia, with a cross-trait genetic correlation of rA = .80, nonshared environmental correlation rE = .89, and a phenotypic correlation of rP = .80. These results are consistent with previous findings in other populations, providing evidence for a similar genetic architecture of these conditions in the multi-ethnic Mexican population.

The global pandemic has accelerated the development of the digital environment, face-to-face work is transferred online, so it is important to create tools adapted to the digital environment. The emergency of Covid-19 has raised the demand for online supervision. In supervision sessions, it is important to talk about experiencing emotions in a professional environment. Latvia lacks digital methods for working with emotions in supervision. The aim of the study was to adapt the 3DEC method, to create it as a web application for use in remote supervision and to approbate the web application "3D emotion composition in supervision" in individual online supervisions. The original method 3DEC is intended for the evaluation of emotional experience in the practice of art therapists (Lejstrauta, 2021; Vanadziņa, 2021). The theoretical basis of the 3DEC method is integrative and includes the following principles: visual representation of emotions in a visible symbolic form; play and play space (Winnicot, 2007); distancing as one of the cognitive emotion regulation strategies (Powers &amp; LaBar, 2019). 3DEC is also based on the Adaptive Coping with Emotions Model (ACE Model) (Berking &amp; Whitley, 2014). The adapted method “3D composition of emotions in supervision” (3DECS) is intended for work in online supervision with the aim to promote awareness of emotions, their understanding and self–reflection. Using distancing and view of other perspectives, the method helps the client to reflect and become aware of emotional experiences, as well as provides an educational function about the meaning of emotions. The 3DECS method develops emotional awareness and adaptive emotion regulation skills. Main results: 1) the web application has been tested and is designed to work with emotions in supervision; 2) the data of the approbation stage show that the web application is sufficiently simple and intuitive; 3) the web application is secure because no information about the customer and the customer's actions in the tool is stored; 4) there are no restrictions on the use of the web application in relation to the duration of the cooperation between the supervisor and the supervision client.