University of Barcelona

Brain network architecture is anticipated to influence future grey matter loss in individuals at Clinical High Risk (CHR) for psychosis. However, existing studies on grey matter structural network properties in CHR are scarce and constrained by small sample sizes. Here, we examined network topology differences comparing a) CHR versus healthy controls (HC); b) CHR who transitioned to psychosis (CHR-T) versus those who did not (CHR-NT); and c) different subsyndromes. We included structural scans from 1842 CHR individuals and 1417 HC individuals from 31 sites within the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium. At the global level, CHR individuals exhibited lower structural covariance (q < 0.001; Cohen's d = 0.164) and less optimal structural network configuration than HC (lower global efficiency and clustering coefficient, d = 0.100,0.087, qs <= 0.027). Though no global difference between CHR-T and CHR-NT, network distinctiveness of the frontal and temporal surface area networks was higher in CHR-T than CHR-NT (d = 0.223,0.237) and HC (d = 0.208,0.219) (qs < 0.001). Network distinctiveness of the frontal cortical thickness network was lower in CHR-T (d = 0.218, q < 0.001) than CHR-NT and HC (d = 0.165, q < 0.001). Importantly, higher network distinctiveness was associated with worse positive symptoms in CHR-NT (frontal surface area, q = 0.008, R2 = 0.013) and at trend with worse negative symptoms in CHR-T (frontal thickness, q = 0.063, R2 = 0.049). Further, the brief intermittent psychotic syndrome subgroup showed more severe network alterations. Together, brain structural networks inform symptoms and the risk of transition to psychosis in CHR individuals.

Despite the growing abundance of sequenced animal genomes, we only have detailed knowledge of regulatory organization for a handful of lineages, particularly flies and vertebrates. These two taxa show contrasting trends in the molecular mechanisms of 3D chromatin organization and long-term evolutionary dynamics of cis-regulatory element (CRE) conservation. Here we study the evolution and organization of the regulatory genome of echinoderms, a lineage whose phylogenetic position and relatively slow molecular evolution have proven particularly useful for evolutionary studies. We generated new reference genome assemblies for two species belonging to two different echinoderm classes: the purple sea urchin Strongylocentrotus purpuratus and the bat sea star Patiria miniata using PacBio and HiC data and characterize their 3D chromatin architecture. We show that these echinoderms have TAD-like domains that, such as in flies, do not seem to be associated with CTCF motif orientation. We systematically profiled CREs during sea star and sea urchin development using ATAC-seq, comparing their regulatory logic and dynamics over multiple developmental stages. Finally, our analysis of sea urchin and sea star CRE evolution across multiple evolutionary distances and timescales showed several thousand elements conserved for hundreds of millions of years, revealing a vertebrate-like pattern of CRE evolution that probably constitutes an ancestral property of the regulatory evolution of animals.

Glucose deficiency promotes the secretion of cytokines and inflammatory factors to rewire the immune compartment and restore blood flow. Here we show that cancer cells subjected to glucose deprivation or hypoxia, but not to other metabolic stressors, secrete LIF, an interleukin-6 family cytokine implicated in the development of solid tumours. We find that mannose supplementation prevents LIF release by sustaining multiple metabolic pathways in the absence of glucose. Mechanistically, LIF release is associated with impairment of N-glycosylation and activation of PERK and MEK MAP kinases. In mouse models of non-small-cell lung cancer, reduction of LIF impairs angiogenesis and tumour growth, rewires the immune system toward an antitumour phenotype and inhibits tumour implantation in the lung. In individuals with non-small-cell lung cancer, LIF levels correlate with markers of hypoxia, glucose deprivation and angiogenesis. Overall, these findings identify LIF as a metabolic stress-induced cytokine that could be targeted to disrupt adaptive responses in cancer.

Background/Objectives: The treatment of dual disorders (DDs) must be comprehensive and multidisciplinary. Evidence supports the effectiveness of psychotherapy in treating DDs. The second part of this consensus synthesizes the available evidence on psychological treatment for specific DDs. Methods: Two consensus methods were sequentially implemented: the nominal group technique and the Delphi method. Results: This consensus review encompassed a compilation of recommendations for the psychological treatment of neurodevelopmental, anxiety, post-traumatic stress, somatic symptom, eating, and personality disorders. Finally, recommendations for the future research agenda on the psychological treatment of DD were included. Conclusions: (1) Psychological treatment, particularly integrated treatment, is effective. (2) In the case of dual autism, interventions for substance use disorders should be adapted to this population's characteristics. (3) More research is needed on dual social anxiety, panic, generalized anxiety, somatic symptom, and eating disorders, for which Cognitive Behavioral Therapy (CBT) is the most commonly used treatment. (4) For dual attention deficit hyperactivity disorder, multicomponent treatment is recommended (psychoeducation, CBT, and peer or family support). (5) For dual anxiety disorders, CBT is the first-line treatment. (6) For dual post-traumatic stress disorder, CBT (cognitive processing therapy and prolonged exposure therapy), acceptance and commitment therapy, stress inoculation training, and Eye Movement Desensitization and Reprocessing (EMDR) are effective. (7) For dual personality disorders, evidence is scarce. (8) For borderline personality disorder, dialectical behavior therapy, dynamic deconstructive psychotherapy, and dual-focus schema therapy show promise. (9) For antisocial personality disorder, CBT, contingency management, and counseling on impulsive lifestyles may be useful. (10) Much more evidence is needed from studies that overcome the methodological limitations of existing ones.

Transcatheter aortic valve implantation (TAVI) has revolutionized the management of aortic stenosis and is now an established alternative to surgical aortic valve replacement (SAVR) for all surgical risk categories. However, the extension of TAVI to younger, low-risk patients has raised important questions regarding the long-term outcomes, valve durability, and lifetime management strategies for these patients. This narrative review summarizes the current evidence from pivotal randomized trials and contemporary registries comparing TAVI and SAVR in young, low-risk patients, integrating the latest 2025 ESC/EACTS guidelines. While short-term outcomes and early recovery favor TAVI, SAVR remains associated with proven durability, lower rates of conduction disturbances, and a potential advantage in long-term outcomes as follow-up data extend beyond five years. Anatomical challenges such as bicuspid valves, coronary access, and patient-prosthesis mismatch further complicate the use of TAVI in this population. A "SAVR-first" lifetime management approach appears to provide greater procedural flexibility and a lower reintervention risk. Ultimately, the choice between TAVI and SAVR in young patients should be individualized through a multidisciplinary Heart Team process, balancing early procedural benefits with long-term durability and reintervention considerations. This review highlights the need for dedicated long-term data and patient-tailored strategies in the evolving management of aortic stenosis in young low-risk individuals.

Adolescence is a critical period for brain development, during which dietary patterns may influence neuropsychological functioning. To examine cross-sectional associations and determine if baseline adherence to the Mediterranean diet (MD) and ultra-processed food (UPF) consumption is associated with changes in adolescent neuropsychological outcomes over 6months. This study represents a secondary analysis of the WALNUTs Smart-Snack Trial. We evaluated 653 adolescents (aged 12-16years) from Barcelona at baseline and at 6-month follow-up. All dietary data used for these analyses were collected at the baseline timepoint only. MD adherence was measured with the KIDMED index and UPF consumption was assessed using a food frequency questionnaire and classified using the NOVA system. Cognitive domains were assessed at both time points using standardised computer-based tasks: attention (alerting, orienting, executive control) with the Attention Network Test; working memory (4-back) with the N-back task; fluid intelligence with the Primary Mental Abilities-Revised; decision-making with the Roulettes Task; and emotion recognition with the Emotion Recognition Task. Behavioural outcomes were also evaluated at both time points using the self-reported Strengths and Difficulties Questionnaire and teacher-reported Attention-Deficit/Hyperactivity Disorder-DSM-IV scales. Associations were examined using multivariable generalised linear models. To further validate UPF consumption estimations, polyphenol biomarkers were measured in urine in a subsample of 257 participants. Greater adherence to the MD was cross-sectionally linked to fewer behavioural problems and higher scores of executive functioning, while higher UPF consumption was associated with poorer emotion recognition, reduced alerting attention, less advantageous decision-making, more behavioural problems and internalising symptoms. Longitudinally, higher UPF consumption was associated with more internalising symptoms and less advantageous decision-making, whereas MD adherence showed no associations. Greater MD adherence appears associated with more favourable behavioural and cognitive profiles. In contrast, higher UPF consumption seems to be associated with less favourable profiles across multiple neuropsychological domains in adolescents. However, the limited longitudinal evidence points to complex relationships that warrant further investigation. Overall, these findings highlight the importance of promoting healthier dietary habits during adolescence.

Expanding the genetic alphabet requires a mechanistic understanding of how synthetic bases are faithfully replicated alongside natural DNA. We present a quantum chemical study reproducing the experimentally observed single-nucleotide incorporation selectivity of Hirao's unnatural base pairs (UBPs) by the 3'-5' exonuclease-deficient Klenow fragment of Escherichia coli DNA polymerase I. Our analysis focuses on the highly selective DsPx pair, benchmarking its behavior against canonical Watson-Crick pairs and other UBPs. Strikingly, the observed selectivity emerges without explicitly modeling the polymerase, relying solely on computed stacking energies within the DNA helix. Molecular orbital and energy-decomposition analyses show that both electrostatic and dispersion interactions strengthen DsPx's affinity more, capturing experimental fidelity trends and explaining its superior performance relative to related systems. We further evaluate other selective UBPs, including QPa, DsPa, and DsPn. Together, these results provide a quantitative framework for UBP incorporation selectivity and highlight the crucial role of noncovalent interactions in stabilizing synthetic bases within DNA. By bridging computation and experiment, this work advances design principles for synthetic genetic systems and contributes to unraveling the molecular origins of DNA replication fidelity.

Structural predictions have reached unprecedented accuracy. They leverage sequence‐specific data to capture all potential interactions a sequence has evolved to fulfill. AlphaFold derives information from three sources: learned parameters capturing intrinsic amino acid secondary structure and environment propensity; models of related proteins providing structural templates; and aligned sequences encoding profiles and concerted evolutionary changes of residues involved in contacts. However, function demands dynamic changes; hence not all possible interactions can coexist simultaneously. Comprehensive information entails contradictions, which resolved in favor of the better‐informed structure will silence less stable states and associations. Here, we introduce a method using all three channels to include prior knowledge: site‐specific variants, predefined alignments and templates. Selecting information relevant to a particular state delimits the functional context of a prediction. Our program VAIRO allows us to rescue asymmetric and weaker interactions to complete the view of molecular assemblies in the architecture of a bacterial surface layer, and reveals otherwise inaccessible dynamic states in a pneumococcal multimeric membrane protein complex. VAIRO is distributed via the python package index (PyPI) (https://pypi.org/project/vairo) and the code is also available on Github (https://github.com/arcimboldo-team/vairo).