Pompeu Fabra University

Background: Acceptance and Commitment Therapy (ACT) has been found to be beneficial for individuals dealing with chronic pain. The theoretical mechanisms of change proposed by ACT are based on the Hexaflex model. To comprehensively reflect this model, the Multidimensional Psychological Flexibility Inventory (MPFI) and Psy-Flex have been developed. The study aimed to adapt the MPFI-24 and the Psy-Flex for Spanish-speaking populations with chronic pain and to examine their dimensionality, internal consistency, convergent validity and incremental validity. Methods: This cross-sectional study involved 309 Spanish-speaking adults with chronic pain who completed an online survey. The majority of the participants were women (88.3%). The ages ranged from 18 to 79 years. Results: Factor analysis showed that the Spanish version of the MPFI-24 has 12 factors, consisting of six flexibility and six inflexibility factors, similar to the original version, but lacking second-order general factors. The Psy-Flex demonstrated a single-factor structure, maintaining the general factor of psychological flexibility seen in the original version. The MPFI-24 showed good internal consistency and adequate convergent validity, with the exception of the Acceptance and Experiential Avoidance subscales. The Psy-Flex showed good internal consistency and convergent validity. Notably, both the MPFI-24 and Psy-Flex scores significantly explained additional variance in psychological distress beyond other ACT-related measures of Hexaflex processes; however, only the Psy-Flex explained pain interference. Conclusions: The Spanish adaptations of the MPFI-24 and Psy-Flex are valid and reliable instruments for assessing the Hexaflex model processes in Spanish-speaking adults with chronic pain. Significance Statement: Practitioners and researchers in chronic pain will find the Spanish versions of the MPFI-24 and the Psy-Flex here, along with ecommendations for their use and scoring based on a robust psychometric rationale. It should be noted that these measures surpass the Chronic Pain Acceptance Questionnaire (CPAQ) and the Psychological Inflexibility in Pain Scale (PIPS), which are considered gold standards in chronic pain assessment.

Although the age of the genome gave us much insight about how our organs fail with disease, it also suggested that diseases do not arise from mutations alone; rather, they develop as we age. In this Review, we examine how wound healing might act to ignite disease. Wound healing works well when we are younger, repairing damage from accidents, environmental assaults, and battles with pathogens. Yet, with age and accumulation of mutations and tissue damage, the repair process can devolve, leading to inflammation, fibrosis, and neoplastic signaling. We discuss healthy wound responses and how our bodies might misappropriate these pathways in disease. Although we focus predominantly on epithelial-based (lung and skin) diseases, similar pathways might operate in cardiac, muscle, and neuronal diseases.

Across all taxa of life, individuals within a species exhibit variable lifespans. Differences in genotype or environment are not sufficient to explain this variance, as even isogenic Caenorhabditis elegans nematodes reared under uniform conditions show significant variability in lifespan. To investigate this phenomenon, we used lifespan‐predictive biomarkers to isolate, at mid‐adulthood, prospectively long‐ and short‐lived individuals from an otherwise identical population. We selected two biomarkers which correlated positively with lifespan, lin‐4p::GFP and mir‐243p::GFP, and two which correlated negatively, mir‐240/786p::GFP and autofluorescence. The gene‐expression signature of long versus short future lifespan was strikingly similar across all four biomarkers tested. Since these biomarkers are expressed in different tissues, these results suggest a shared connection to a global health state correlated with future lifespan. To further investigate this underlying state, we compared the transcriptional signature of long versus short future lifespan to that of chronologically young versus old individuals. By comparison to a high‐resolution time series of the average aging transcriptome, we determined that subpopulations predicted to be long‐ or short‐lived by biomarker expression had significantly different transcriptional ages despite their shared chronological age. We found that this difference in apparent transcriptional age accounted for the majority of differentially expressed genes associated with future lifespan. Interestingly, we also identified several genes whose expression consistently separated samples by biomarker expression independent of apparent transcriptional age. These results suggest that the commonalities in the long‐lived versus short‐lived state reported across different biomarkers of aging extends beyond simply transcriptionally young versus transcriptionally old.

Introduction Adverse perinatal outcomes (APO) pose a significant global challenge, particularly in low- and middle-income countries (LMICs). This study aims to analyse two cohorts of high-risk pregnant women for APO to comprehend risk factors and improve prediction accuracy. Methods We considered an LMIC and a high-income country (HIC) population to derive XGBoost classifiers to predict low birth weight (LBW) from a comprehensive set of maternal and fetal characteristics including socio-demographic, past and current pregnancy information, fetal biometry and fetoplacental Doppler measurements. Data were sourced from the FeDoC (Fetal Doppler Collaborative) study (Pakistan, LMIC) and theIMPACT (Improving Mothers for a Better PrenAtal Care Trial) study (Spain, HIC), and included 520 and 746 pregnancies assessed from 28 weeks gestation, respectively. The models were trained on varying subsets of the mentioned characteristics to evaluate their contribution in predicting LBW cases. For external validation, and to highlight potential differential risk factors for LBW, we investigated the generalisation of these models across cohorts. Models’ performance was evaluated through the area under the curve (AUC), and their interpretability was assessed using SHapley Additive exPlanations. Results In FeDoC, Doppler variables demonstrated the highest value at predicting LBW compared with biometry and maternal clinical data (AUCDoppler, 0.67; AUCClinical, 0.65; AUCBiometry, 0.63), and its combination with maternal clinical data yielded the best prediction (AUCClinical+Doppler, 0.71). In IMPACT, fetal biometry emerged as the most predictive set (AUCBiometry, 0.75; AUCDoppler, 0.70; AUCClinical, 0.69) and its combination with Doppler and maternal clinical data achieved the highest accuracy (AUCClinical+Biometry+Doppler, 0.81). External validation consistently indicated that biometry combined with Doppler data yielded the best prediction. Conclusions Our findings provide new insights into the predictive role of different clinical and ultrasound descriptors in two populations at high risk for APO, highlighting that different approaches are required for different populations. However, Doppler data improves prediction capabilities in both settings, underscoring the value of standardising ultrasound data acquisition, as practiced in HIC, to enhance LBW prediction in LMIC. This alignment contributes to bridging the health equity gap.

Quiescent cells require a continuous supply of proteins to maintain protein homeostasis. In fission yeast, entry into quiescence is triggered by nitrogen stress, leading to the inactivation of TORC1 and the activation of TORC2. In this study, we demonstrate that the Greatwall-Endosulfine-PPA/B55 pathway connects the downregulation of TORC1 with the upregulation of TORC2, resulting in the activation of Elongator-dependent tRNA modifications crucial for sustaining the translation programme during entry into quiescence. This mechanism promotes U34 and A37 tRNA modifications at the anticodon stem loop, enhancing translation efficiency and fidelity of mRNAs enriched for AAA versus AAG lysine codons. Notably, several of these mRNAs encode TORC1 inhibitors, TORC2 activators, tRNA modifiers, and proteins necessary for telomeric and subtelomeric functions. Therefore, we propose a mechanism by which cells respond to nitrogen stress at the level of translation, involving a coordinated interplay between tRNA epitranscriptome and biased codon usage.

The making of international law through multilateral conventions and adjudication often leads to periods of legal uncertainty, times in which there are alternative rules and divergent views on how they ought to be applied to particular cases. I argue that legal uncertainty gives states opportunities and incentives to formulate excessive unilateral claims, thus making disputes more likely to arise. I illustrate my argument with a comprehensive analysis of maritime boundary disputes in the aftermath of the Second World War. In this period, the law regulating maritime boundary-making has been marked by varying degrees of uncertainty due to different rules and interpretations proffered by various multilateral and judicial lawmaking attempts. I find strong evidence that high legal uncertainty is associated with an increased probability of dispute onset. The analysis calls for an important rethinking of the impact of legalization on international affairs, both in maritime boundary-making and in other issues areas.

This article summarizes selected poster presentations from the 2024 Fall Clinical Dermatology Conference (FCDC), with a focus on updated data for tralokinumab in atopic dermatitis (AD) and delgocitinib cream in chronic hand eczema (CHE), and how these treatments could tackle unmet needs. Presentations on the IL-13 receptor inhibitor tralokinumab included final data from the long-term, open-label extension study ECZTEND, of patients with moderate-to-severe AD exposed to tralokinumab for up to 6 years, as well as evaluations of the treatment’s long-term safety and efficacy in patients aged ≥65 years. An indirect comparison of tralokinumab and lebrikizumab indicated their efficacy was similarly maintained over 1 year. Real-world data for tralokinumab in AD were presented from several studies, including three interim analyses of the TRACE study, which assessed tralokinumab efficacy in AD on specific regions of the body. Delgocitinib cream is a topical pan-JAK inhibitor recently approved in the EU for moderate-to-severe CHE in adults for whom topical corticosteroids (TCS) are inadequate or inappropriate. Several posters presented data from a pooled post hoc analysis of Phase III trials DELTA 1 and DELTA 2, demonstrating that delgocitinib led to meaningful improvements in clinical signs and patient-reported outcomes, and was well-tolerated over 16 weeks of treatment. One poster showed that twice-daily application of delgocitinib cream 20 mg/g for 16 weeks resulted in minimal systemic exposure, and two reported favorable efficacy and safety of delgocitinib compared with systemic therapies, including data from the DELTA FORCE trial. Overall, presented data supported the benefits of delgocitinib as an efficacious and well-tolerated topical treatment in a patient population that faces a high disease burden and has unmet treatment needs.

White matter (WM) tracts shape the brain's dynamical activity and their damage (e.g., white matter hyperintensities, WMH) yields relevant functional alterations, ultimately leading to cognitive symptoms. The mechanisms linking the structural damage caused by WMH to the arising alterations of brain dynamics is currently unknown. To estimate the impact of WMH on brain dynamics, we combine neural‐mass whole‐brain modeling with a virtual‐lesioning (disconnectome) approach informed by empirical data. We account for the heterogeneous effects of WMH either on inter‐regional communication (i.e., edges) or on dynamics (i.e., nodes) and create models of their local versus global, and edge versus nodal effects using a large fMRI dataset comprising 188 non‐demented individuals (120 cognitively normal, 68 with mild cognitive impairment) with varying degrees of WMH. We show that, although WMH mainly determine local damage to specific WM tracts, these lesions yield relevant global dynamical effects by reducing the overall synchronization of the brain through a reduction of global coupling. Alterations of local nodal dynamics through disconnections are less relevant and present only at later stages of WMH damage. Exploratory analyses suggest that education might play a beneficial role in counteracting the reduction in global coupling associated with WMH. This study provides generative models linking the structural damage caused by WMH to alterations in brain dynamics. These models might be used to evaluate the detrimental effects of WMH on brain dynamics in a subject‐specific manner. Furthermore, it validates the use of whole‐brain modeling for hypothesis‐testing of structure–function relationships in diseased states characterized by empirical disconnections.

We present MoCHI, a tool to fit interpretable models using deep mutational scanning data. MoCHI infers free energy changes, as well as interaction terms (energetic couplings) for specified biophysical models, including from multimodal phenotypic data. When a user-specified model is unavailable, global nonlinearities (epistasis) can be estimated from the data. MoCHI also leverages ensemble, background-averaged epistasis to learn sparse models that can incorporate higher-order epistatic terms. MoCHI is freely available as a Python package (https://github.com/lehner-lab/MoCHI) relying on the PyTorch machine learning framework and allows biophysical measurements at scale, including the construction of allosteric maps of proteins.

We show that for a wide range of channels and code ensembles with pairwise-independent codewords, with probability tending to 1 with the code length, expurgating an arbitrarily small fraction of codewords from a randomly selected code results in a code attaining the expurgated exponent.

Background Loneliness, a major public health concern, could be alleviated through social interventions with nature contact as a primary component. “Friends in Nature” is a complex nature-based social intervention designed to be implemented as part of “Reimagining Environments for Connection and Engagement: Testing Actions for Social Prescribing in Natural Spaces" (RECETAS). This project aims to alleviate loneliness and promote health-related quality of life in six different geographic areas worldwide. Feasibility studies are crucial to assess the viability of complex interventions and study procedures before conducting definitive studies. This paper aims to describe the design, implementation, and evaluation of the six-related feasibility studies on the “Friends in Nature” intervention. These studies specifically evaluate feasibility of recruitment and study procedures, intervention implementation, and data collection and distribution. Methods We defined a comprehensive set of indicators to assess the feasibility of “Friends in Nature.” For the first domain, recruitment procedures were assessed to determine their adequacy, while attrition rates were examined to assess participant retention. For the second domain, the implementation of interventions was evaluated, along with the study design’s ability to adapt to unexpected situations and participant adherence to the intervention. Finally, for the third domain, completion rates and the acceptability of the study activities were also analyzed. The feasibility of using specific scales to assess loneliness and well-being was also explored. Results The feasibility indicators defined for this study were useful to assess the feasibility of “Friends in Nature.” Recruitment procedures were generally found to be adequate, and the number of dropouts was low. Interventions were implemented with minor adjustments, and facilitators played a vital role in the well-functioning of the interventions. Although some unexpected situations occurred during the study, adaptations were made, and participants were generally satisfied with the activities proposed. Scales used to assess loneliness and quality of life showed potential for measuring the effects of nature-based social prescribing in the full trial. Conclusion This paper offers valuable insights into the design and execution of feasibility studies for complex interventions like “Friends in Nature.” Findings from these assessments explore the feasibility of “Friends in Nature” and will inform the main RECETAS studies, which are designed to strengthen the evidence base to support the use of nature-based social prescribing to reduce loneliness and promote quality of life. Trial registration Barcelona trial: NCT05488496, Prague trial: NCT05522140, and Helsinki trial: NCT05507684.

Against the background of increased labor market flexibilization, health issues amongst employees have become a pressing social concern in Korea. Yet, little is known about the diversity in employment experiences and the associated health implications amongst employees. To accurately gauge labor market segmentation, whilst simultaneously accounting for health-risk factors, we employ the multidimensional Employment Quality (EQ) concept in a typological manner. This method differentiates various employment segments, with the Standard Employment Relationship (SER) serving as a benchmark. Using the 2017 Korean Working Conditions Survey (KWCS), we employ Latent Class Cluster Analysis on a sample of the salaried workforce (N = 25.376) to construct a typology of EQ. Via logistic regression, we link the EQ typology to poor mental well-being and poor self-rated general health. As a result, we find six distinct types of EQ arrangements in Korea: SER-like, Instrumental, SER Intensive, Instrumental Intensive, Precarious Intensive, and Precarious Unsustainable. We find that deviations from the SER-like segment are associated with poorer health and well-being outcomes, even when accounting for confounding factors, with precarious EQ segments showing the most pronounced adverse health and well-being associations. This study furthers our understandings of health disparities within the salaried workforce. Our findings underscore the need for targeted reforms of workplace- and employment-related health policies to foster a healthier working population in Korea.

The biological relevance and dynamics of mRNA modifications have been extensively studied; however, whether rRNA modifications are dynamically regulated, and under which conditions, remains unclear. Here, we systematically characterize bacterial rRNA modifications upon exposure to diverse antibiotics using native RNA nanopore sequencing. To identify significant rRNA modification changes, we develop NanoConsensus, a novel pipeline that is robust across RNA modification types, stoichiometries and coverage, with very low false positive rates, outperforming all individual algorithms tested. We then apply NanoConsensus to characterize the rRNA modification landscape upon antibiotic exposure, finding that rRNA modification profiles are altered in the vicinity of A and P-sites of the ribosome, in an antibiotic-specific manner, possibly contributing to antibiotic resistance. Our work demonstrates that rRNA modification profiles can be rapidly altered in response to environmental exposures, and provides a robust workflow to study rRNA modification dynamics in any species, in a scalable and reproducible manner.

Background: The ability to age healthily is highly dependent on individual characteristics that include gender, social class, a range of biological and contextual factors, and migrant background. Indeed, immigration has changed the demographic composition and social structure of many European countries, generating an increasing interest in how societies, and immigrants in particular, are aging. Research Design: This paper compares the age-related trajectories of health decline in three health measures (activity limitation indicator, self-perceived health, and chronic conditions) among 7,429 immigrants and 81,424 native-born populations aged 50 years old and over using longitudinal data from seven waves of the Survey of Health, Ageing and Retirement in Europe (SHARE) (2004–2020). Analysis: We use descriptive and multivariate models (random-effects regression models) to analyze the association between migration status and each health outcome. We are particularly interested in determining the age-related trajectory of this association across three levels of education, exploring at the same time the effect of the interaction between immigration status and age on health. Results: Our results highlight potential gaps in health between immigrants and native-born people that are particularly large for the low-educated group. In other words, the health decline is more marked for low-educated immigrants compared to native-born populations in particular for activity limitation indicator and self-perceived health, while it is less pronounced with the accumulation of chronic conditions. Conclusions: Our findings should serve to enhance the design of the provision of social services and support and the promotion of equal opportunities.

Purpose The phenomenon of avoidable care transitions has received increasing attention over the last decades due to its frequency and associated burden for the patients and the healthcare system. A number of assessment tools to identify avoidable transitions have been designed and implemented. The selection of the most appropriate tool appears to be challenging and time-consuming. This systematic review aimed to identify and comprehensively describe the assessment tools that can support stakeholders´ care transition decisions on older adults. Methods This study was conducted as part of the TRANS-SENIOR research network. A systematic search was conducted in MEDLINE via PubMed, CINAHL, and CENTRAL. No restrictions regarding publication date and language were applied. Results The search in three electronic databases revealed 1266 references and screening for eligibility resulted in 58 articles for inclusion. A total of 48 assessment tools were identified covering different concepts, judgement processes, and transition destinations. We found variation in the comprehensiveness of the tools with regard to dimensions used in the judgement process. Conclusion All tools are not comprehensive with respect to the dimensions covered, as they address only one or a few perspectives. Although assessment tools can be useful in clinical practice, it is worth it to bear in mind that they are meant to support decision-making and supplement the care professional´s judgement, instead of replacing it. Our review might guide clinicians and researchers in choosing the right tool for identification of avoidable care transitions, and thus support informed decision-making.

Freshwater planarians constitute an important component in aquatic ecosystems as predators. They are, nonetheless, delicate animals used as indicators of water quality. This group has been little studied in The Antilles, where only seven species of Girardia Ball, 1974 have been reported. Those records date from the last two centuries and were identified based on morphology, leaving several specimens unidentified. Furthermore, the anatomical similarities among species and the lack of the copulatory apparatus in fissiparous populations make it necessary to use molecular data to perform accurate species delimitations and phylogenetic studies. The Cuban archipelago is the reservoir of the highest species diversity in the Caribbean. However, only one species of freshwater triclad has been described, Girardia cubana (Codreanu & Balcesco, 1973), which is endemic to Cuba. Recent samplings in the western part of the island molecularly identified Girardia sinensis Chen & Wang, 2015. At present, we are performing broad samplings all around Cuba. As a first result, we here present a phylogeny-based identification of freshwater planarians, collected in four localities of eastern Cuba, inferred using nuclear and mitochondrial markers. The presence of G. sinensis in the eastern part of the island is reported and two other lineages of the genus are identified, at least one could be a new species. Moreover, we found a lineage belonging to Cavernicola, of which there are no previous records in The Antilles. These findings support that the planarian richness of Cuba has been underestimated and new species could be described, providing relevant biogeographic information about the group in the Caribbean. KEY WORDS: Antilles; Caribbean; Cavernicola; Dugesiidae; Girardia; Rhodax

Recent advancements in protein structure determination are revolutionizing our understanding of proteins. Still, a significant gap remains in the availability of comprehensive datasets that focus on the dynamics of proteins, which are crucial for understanding protein function, folding, and interactions. To address this critical gap, we introduce mdCATH, a dataset generated through an extensive set of all-atom molecular dynamics simulations of a diverse and representative collection of protein domains. This dataset comprises all-atom systems for 5,398 domains, modeled with a state-of-the-art classical force field, and simulated in five replicates each at five temperatures from 320 K to 450 K. The mdCATH dataset records coordinates and forces every 1 ns, for over 62 ms of accumulated simulation time, effectively capturing the dynamics of the various classes of domains and providing a unique resource for proteome-wide statistical analyses of protein unfolding thermodynamics and kinetics. We outline the dataset structure and showcase its potential through four easily reproducible case studies, highlighting its capabilities in advancing protein science.