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Artificial intelligence in thoracic surgery consultations: evaluating the concordance between a large language model and expert clinical decisions
(Frontiers Media, 2025-11-17) Déniz Armengol, Carlos; Marcè, Judith; Macía, Ivan; Rivas Doyague, Francisco; Muñoz, Ana; Paradela, Marina; García, Sonia; Moreno, Camilo; Serratosa, Inés; García, Marta; Rodríguez-Martos, Tania; Ojanguren, Amaia
Background: Artificial intelligence (AI) and large language models (LLMs) are increasingly used in clinical workflows, but their real-world application in thoracic surgery decision-making remains underexplored. Methods: This retrospective observational study assessed the concordance between diagnostic and therapeutic recommendations generated by Scholar GPT (based on GPT-4) and decisions made by board-certified thoracic surgeons. All outpatient consultations over one week in a tertiary care hospital were included. Each case was evaluated using a 6-point concordance scale (0–5), developed to quantify agreement in diagnosis and treatment planning. This was a retrospective observational, single-centre analysis; two independent thoracic surgeons assigned the concordance score. We report descriptive statistics and used t-tests/ANOVA for continuous variables and chi-square tests for categorical variables. Given the exploratory design, no a priori sample-size calculation or power analysis was performed. Results: A total of 81 consultations were analysed. The mean concordance score was 3.67 ± 1.17. High concordance (scores 4–5) occurred in 56.8% of cases, particularly in oncological diagnoses such as mediastinal and pleural tumours. Lower concordance was observed in complex or functional conditions like metastatic lung disease and thoracic outlet syndrome. No significant differences were found between consultation modalities or visit types. Conclusion: Scholar GPT demonstrated promising alignment with surgeon decisions in structured oncologic cases but showed variability in complex scenarios. While AI may assist in streamlining outpatient workflows, its use should remain complementary to expert clinical judgment. These findings are exploratory and should be interpreted with caution given the small sample size and single-centre, one-week design.
Managing Enterococcus faecium bloodstream infection: a Delphi document on clinical recommendations and research agenda
(Elsevier, 2026-05-02) Rinaldi, Matteo; Bartoletti, Michele; Cojutti, Piergiorgio; Escolà Vergé, Laura; Fernández Hidalgo, Nuria; Hornuss, Daniel; Gatti, Milo; Gudiol González, Carlota; Gutiérrez-Gutiérrez, Belén; López Cortés, Luis E.; Kern, Winfried V.; Los-Arcos, Ibai; Muñoz, Patricia; Oliva, Alessandra; Papadimitriou-Olivgeris, Matthaios; Pai, Manjunath; Pea, Federico; Pericàs, Juan M.; Rieg, Siegbert; Russo, Alessandro; Soriano Viladomiu, Alex; Thursky, Karin; Udy, Andrew; Venditti, Mario; Yahav, Dafna; Mo, Yin; Viale, Pierluigi; Giannella, Maddalena
Background: Management of E faecium bloodstream infections (BSIs) remains debated, particularly the clinical impact of vancomycin resistance, the role of follow-up cultures, and optimal therapeutic regimens. This study aimed to reach expert consensus on these unresolved clinical domains and identify priorities for future research. Methods: We first conducted a systematic review and meta-analysis in January 20, 204 focusing on four predefined areas: mortality in E faecium BSIs compared with other BSIs, mortality in vancomycin-resistant enterococci (VRE)-BSIs compared with vancomycin-susceptible enterococci-BSIs, management of catheter-related E faecium BSIs, and 4) optimal antibiotic therapy for VRE-BSIs. These results informed a three-round Delphi process involving a panel of experts. An iterative approach was adopted: 16 initial questions developed from the systematic review (6-point Likert scale) were refined across rounds based on expert feedback. Consensus was defined as at least 80% agreement or disagreement. Findings: 13 statements were generated across three broader domains. Regarding clinical outcomes and diagnostics, experts agreed that mortality is heavily influenced by comorbidities; thus, therapeutic assessment should rely on clinical trends and inflammatory markers, with follow-up blood cultures used to confirm eradication. Catheter-related BSI should be managed with device removal and short-course (<7 days) antibiotics in selected uncomplicated cases. For therapeutic management, teicoplanin is preferred for vanB VRE-BSI. For vanA VRE-BSI, both linezolid and high-dose daptomycin (>9 mg/kg per day) are effective, reserving daptomycin-based combinations for challenging cases (deep-seated infections and/or high Minimum Inhibitory Concentrations). Finally, future trials evaluating the impact of antimicrobial therapy should use Desirability-of-Outcome-Ranking analysis; the in-vitro potential of oritavancin justifies targeted randomized trials to define its clinical efficacy in VRE-BSI. Interpretation: This paper delineates current evidence and expert consensus on management of E faecium BSI while identifying crucial knowledge gaps to guide future clinical research.
Genetic risk factors modulate the association between physical activity and colorectal cancer
(BioMed Central, 2026-03-09) Peoples, Anita R.; Obón Santacana, Mireia; Kim, Andre E.; Kawaguchi, Eric S.; Fu, Yubo; Qu, Conghui; Moratalla Navarro, Ferran; Morrison, John; Lin, Yi; Arndt, Volker; Berndt, Sonja I.; Bien, Stephanie A.; Bishop, D. Timothy; Bouras, Emmanouil; Brenner, Hermann; Buchanan, Daniel D; Campbell, Peter T.; Chan, Andrew T.; Chang-Claude, Jenny; Conti, David V.; Corley, Douglas A.; Devall, Matthew A.; Dimou, Niki; Drew, David A.; Gruber, Stephen B.; Gunter, Marc J.; Harlid, Sophia; Harrison, Tabitha A.; Hoffmeister, Michael; Hsu, Li; Huyghe, Jeroen R.; Keku, Temitope O.; Kundaje, Anshul; Lewinger, Juan Pablo; Li, Li; Lynch, Brigid M.; Le Marchand, Loïc; Martín, Vicente; Murphy, Neil; Newton, Christina C.; Ogino, Shuji; Hardikar, Sheetal; Ose, Jennifer; Pai, Rish K.; Palmer, Julie R.; Papadimitriou, Nikos; Pardamean, Bens; Pellatt, Andrew J.; Pinchev, Mila; Platz, Elizabeth A.; Potter, John D.; Rennert, Gad; Ruiz-Narvaez, Edward; Sakoda, Lori C.; Schoen, Robert E.; Shcherbina, Anna; Stern, Marianna C.; Su, Yu-Ru; Thomas, Claire E.; Tian, Yu; Tsilidis, Konstantinos K.; Um, Caroline; van Duijnhoven, Franzel J.B.; Van Guelpen, Bethany; Visvanathan, Kala; Wang, Junzhi; White, Emily; Wolk, Alicja; Woods, Michael O.; Wu, Anna H.; Ulrich, Cornelia M.; Peters, Ulrike; Gauderman, W. James; Moreno Aguado, Víctor
Background: Physical activity is an established protective factor for colorectal cancer (CRC), but it is unclear if genetic variants modify this effect. To investigate this possibility, we conducted a genome-wide gene–physical activity interaction analysis. Methods: Using logistic regression (1-d.f), two-step screening and testing method (EDGE), and joint tests (3-d.f), we analyzed interactions between common genetic variants across the genome and physical activity in relation to CRC risk. Self-reported physical activity levels were categorized as active (≥ 8.75 MET-h/wk) vs. inactive (< 8.75 MET-h/wk; 39,992 participants) and as study- and sex-specific quartiles of activity (42,602 participants). Results: Physical activity was inversely associated with CRC risk overall (OR [active vs. inactive] = 0.85; 95% CI = 0.81–0.90). The two-step EDGE method identified an interaction between rs4779584, an intergenic variant near the GREM1 and SCG5 genes, and physical activity for CRC risk (p-interaction = 2.6 × 10−8). Stratification by genotype at this locus showed a significant reduction in CRC risk by 20% in active vs. inactive participants with the CC genotype (OR = 0.80; 95% CI = 0.75–0.85), but no significant physical activity–CRC associations among CT or TT carriers. When physical activity was modeled as quartiles, the 1-d.f. test identified that rs56906466, an intergenic variant near the KCNG1 gene, modified the association between physical activity and CRC (p-interaction = 3.5 × 10−8). Stratification at this locus showed that an increase in physical activity (highest vs. lowest quartile) was associated with a lower CRC risk solely among TT carriers (OR = 0.77; 95% CI = 0.72–0.82). Conclusions: In summary, we identified two genetic variants that modified the association between physical activity and CRC risk. One of them, related to GREM1 and SCG5, suggests that the bone morphogenetic protein (BMP)-related, inflammatory, and/or insulin signaling pathways may be involved in the protective association between physical activity and colorectal carcinogenesis.
Inequities in Waiting Times for Major Elective Surgery Before and After the COVID-19 Pandemic: Socioeconomic and Sex Differences in the Southern Barcelona Metropolitan Area
(MDPI, 2026-03-01) Pericas Escale, Carles; Vilaplana Carnerero, Carles; Poltorak, Violeta; Redondo, Ana; Masuet Aumatell, Cristina; Tor Roca, Alba; Pagès Fernández, Constança; Grau, María
Background: Waiting times for elective surgery are widely used as indicators of health system performance, particularly following the disruption caused by COVID-19. The objective of this study is to compare the waiting times for major elective surgeries in the Southern Barcelona Metropolitan Area before (2018–2019) and after (2022–2023) the pandemic, examining differences according to sociodemographic characteristics. Methods: A retrospective comparative study was conducted using data from the Southern Barcelona Metropolitan Area between 2018 and 2023. Adults registered on the waiting list for major elective surgical procedures were included. All analyses were stratified by sex. A stratified pre–post pandemic analysis was conducted to examine differences in waiting times by Socioeconomic Index. Waiting times were modelled using generalized linear models with a Gamma distribution and log link, adjusting for age and Socioeconomic Index quartiles. Interaction between period and Socioeconomic Index was tested. Results: The analysis included 73,055 individuals (50.5% women). Median waiting time decreased after the COVID-19 pandemic for both sexes (women: 128 to 121 days; men: 99 to 94 days). This reduction showed an inverse socioeconomic gradient. Adjusted analyses showed longer waits in the lowest versus highest Socioeconomic Index quartile after the pandemic (women: RR = 1.23; men: RR = 1.30). Conclusions: Waiting times for major elective surgery decreased after COVID-19. An exclusive focus on waiting time indicators may conceal structural barriers to access and contribute to inequalities. Equity-sensitive monitoring of elective care is essential to ensure a fair recovery of surgical services.
Inpatient hospital admissions for people with obsessive-compulsive disorder (OCD). A position statement by the international college of obsessive-compulsive spectrum disorders
(Elsevier B.V., 2026-04) Brakoulias, Vlasios; Albert, Umberto; Chamberlain, Samuel R.; Dell'Osso, Bernardo; Ferretti, Casara J.; Girone, Nicolaja; Hollander, Eric, 1957-; Ioannidis, Konstantinos; Lochner, Christine; Menchón Magriñá, José Manuel; Mpavaenda, Davis; Pallanti, Stefano; Pampaloni, Ilenia; Pellegrini, Luca; Stein, Dan J., 1962-; Van Ameringen, Michael; Zohar, Joseph; Fineberg, Naomi A.
Background: The hospitalization of patients with obsessive-compulsive disorder (OCD) is less common in comparison to other mental disorders, and often a significant and distressing event. Objectives: This paper presents a position statement, developed by the International College of Obsessive-Compulsive Spectrum Disorders, on the indications for hospital admission for people with OCD, the treatment that is offered within hospital, the complications that may occur in this setting, and principles for best practice. Methods: Current literature was critically reviewed and narratively synthesized by a group of international experts in the field of OCD. Results; An inpatient hospital admission may be required for people with severe OCD who are unable to accept or tolerate pharmacological or psychological treatment as an outpatient or where there would be significant risks to the individual or those around them. Admissions have been associated with significant reductions in OCD severity. Inpatient treatment often involves psychoeducation of staff, patients and family members, pharmacotherapy, exposure and response prevention psychological work, addressing comorbidity as well as psychosocial issues such as family-relational issues, homelessness, grief or loss. Admissions can be distressing, and intensive inpatient-based therapy programs require the comprehensive assessment of risk. Conclusions: The inpatient treatment of people with OCD is an important management option that needs to be well considered and managed. Admissions often require close monitoring of risks, additional support to staff who may be unfamiliar with OCD, addressing comorbidity, pharmacotherapy and exposure and response prevention therapy.
Iron Matters: Comparative Impact of Beta-Adrenergic Stimulation and Iron Chelation on Cardiac Iron Metabolism and Mitochondrial Function
(MDPI, 2026-04-14) Francesch Manzano, Josep; Comín Colet, Josep; Tajes Orduña, Marta; Ramos Polo, Raúl; Enjuanes, Cristina; Ras Jiménez, Maria del Mar; Cosa, Andreea Eunice; Marinova, Katrin; Enrich Soria, Carla; Moliner, Pedro; Lorenzo Esteller, Laia; Jose Bazán, Núria
Iron deficiency (ID) is frequent in patients with heart failure (HF) and is correlated with adverse outcomes, yet its involvement in HF pathophysiology is not fully understood. Hyperactivity of the sympathetic nervous system (SNS) is the central feature of HF. We aimed to compare the effects of isoproterenol (ISO), a β-adrenergic agonist (SNS stimulation), with those of the iron chelator deferoxamine (DEF), to evaluate how β-adrenergic stimulation influences cardiac iron. In this study, H9c2 cardiac cells were challenged with ISO, DEF or both and several parameters related to iron metabolism were analyzed. In all cases, the cells decreased their intracellular iron levels. ISO induced alterations in key cardiac iron metabolism molecules that were, in most cases, comparable to those elicited by DEF, emphasizing the direct impact of β-adrenergic stimuli on iron metabolism and mitochondrial dysfunction. Nevertheless, unlike DEF, ISO triggered a shift in mitochondrial energy metabolism. These findings suggest that β-adrenergic stimulation, as a major component of neurohormonal activation, may contribute to the development of ID in cardiac cells, highlighting the importance of iron homeostasis and the need to further investigate iron dysregulation in this context.
Indocyanine green fluorescence for intraoperative detection of liver tumours in minimally invasive surgery: protocol for the LIVERGREEN phase IV multicentre clinical trial
(BMJ Publishing Group, 2026-04-16) Huerta, Martín; López Ben, Santiago; Lladó Garriga, Laura; Sánchez Cabús, Santiago; Mils, Kristel; Molina, Víctor; Dopazo, Cristina; Vidal, Laura; Dalmau, Mar; Caralt, Mireia; Rosón, Núria; Merino, Xavier; Armario, David; Salcedo Allende, María Teresa; Pellino, Gianluca; Sapisochin, Gonzalo; Gómez Gavara, Concepción; Pérez, Núria; Roig, Anna; Sanjuan, Anna; Pérez, Santiago; Sánchez Maroto, Olga; Delgado, Esther; Cabau, Claudia; Villasante, Sara; Galiana, Carmen; Herms, Daniel; Valencia, Sebastián; Cañete, Marta; García, Oliver; Barrios, Oriana; Vila, Marina; Leiva Ureña, David; Layreda, Karen
Introduction: Liver tumours are a leading cause of global morbidity and mortality. Current diagnostic tools, including computed tomography (CT), magnetic resonance imaging (MRI) and intraoperative ultrasound (IOUS), have limitations in detecting liver neoplasms. Indocyanine green (ICG) has emerged as a promising tool for improving liver tumour detection. This study aims to assess the impact of preoperative ICG on intraoperative tumour detection in minimally invasive surgery and develop a machine-learning algorithm to enhance tumour detection using ICG fluorescence. Methods and analysis: This prospective, multicentre, phase IV clinical trial adheres to Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines. Patients with liver tumours eligible for minimally invasive surgery and a preoperative imaging test will be included. ICG will be administered intravenously 24 hours before surgery. Intraoperative procedures will include IOUS, ICG mapping and photographic documentation. Patients will be followed for 90 days to assess tumour progression, morbidity and mortality. The photographic analysis will enable the development of an artificial intelligence algorithm using machine learning and neural networks to identify lesions based on ICG fluorescence. The estimated sample size is 173 patients and the trial is predicted to accrue in 3 years. Ethics and dissemination: The trial will be conducted in accordance with the Declaration of Helsinki and the Spanish Agency of Medicines and Medical Devices (AEMPS) guidelines. Approved by the local institutional Ethics Committee and the AEMPS, the results will be shared with the scientific community through publications and conferences.
Enhancing Type 1 Diabetes Polygenic Risk Prediction Through Neural Networks and Entropy-Derived Insights
(MDPI, 2026-03-25) Nadal Martínez, Antonio; Pérez Solero, Guillermo; Ferreiro López, Sandra; Blom Dahl, Jorge; Montanya Mias, Eduard; Alonso Bernáldez, Marta; Shabot, Moises; Binsch, Christian; Szczerbinski, Lukasz; Kretowski, Adam; Nevado, Julián; Lapunzina, Pablo; Wagner, Robert; Tenorio Castano, Jair
Type 1 diabetes (T1D) is an autoimmune disease with a strong genetic component (~70% heritability). Early identification of individuals at risk is crucial for early intervention or risk assessment. Although polygenic risk scores (PRS) have shown promise in risk assessment, most current approaches remain constrained by linear assumptions and limited generalizability. We aimed to develop a neural network-driven classifier using T1D-associated single nucleotide polymorphisms (SNPs). In addition, we explored the inclusion of an entropy-derived feature as a complementary variable, representing the degree of genetic variability within an individual’s genotype profile across the 67 T1D-associated SNPs, to evaluate its potential additive contribution to the model performance. We analyzed genotype data from 11,909 individuals in the UK BioBank (546 T1D cases and 11,363 controls). Sixty-seven well-known SNPs associated with T1D were utilized as inputs to the model, using two distinct allele-encoding strategies. A feed-forward neural network was evaluated under varying case–control ratios through five-fold cross-validation. Performance was assessed using the area under the receiver operating characteristic curve (AUC) on a held-out test set and on an external European cohort as a validation cohort. Across five-fold cross-validation, the best configuration achieved a median AUC of 0.903. On the held-out UK Biobank test set, the model generalized well, with an AUC of 0.8889 (95% CI: 0.8516–0.9262). A probability-based risk framework, constructed using five risk groups (“very low”, “low”, “intermediate”, “high”, and “very high” risk), yielded a negative predictive value (NPV) of 98.9% for the “very low” risk group and a Positive Predicted Value (PPV) of 61.9% with a specificity of 97.3% for the “very high” risk group, assuming a 10% T1D prevalence. External validation in the German Diabetes Study reproduced clear case–control separation; for individuals with recent onset diabetes and glutamic acid decarboxylase antibodies (GADA+) vs. controls, specificity reached 91.9% in the “high” risk group (PPV of 94.3%) and 97.6% in the “very high” risk group (PPV of 95.7%). The proposed neural network reliably predicts T1D genetic risk using a compact SNP panel of 67 SNPs and maintains accuracy in both internal and external European cohorts. Its probabilistic output enables clinically interpretable risk thresholds, while entropy features contributed modestly to performance. These results demonstrate that a neural network-based approach achieves discriminative performance that is comparable to established T1D genetic risk models, while offering flexible probability-based risk stratification and architectural extensibility for future integration of additional features.
Linear Accelerator Mask–Based Radiosurgery for Trigeminal Neuralgia: Prospective Evaluation of 50 Patients
(Elsevier, 2026-04) Rosselló Gómez, Aleix; Modolell Farré, Ignasi; Macià Garau, Miquel; Lucas Calduch, Anna; García Expósito, Nagore; Muñoz Vendrell, Albert; Campoy Diaz, Sergio; Huerta Villanueva, Mariano; Majós Torró, Carlos; Cos Domingo, Mònica; Cifre Serra, Pere Josep; Picón, Cristina; Gabarrós Canals, Andreu; Guedea Edo, Ferran
Background: Trigeminal neuralgia (TN) resistant to pharmacologic treatment can be treated with microvascular decompression, percutaneous procedures, or radiosurgery. Regarding radiosurgery, there is variability in target definition, dose selection, radiation delivery and positioning, and immobilization. Methods: This observational prospective study included patients with TN treated with 90 Gy prescribed to an anterior cisternal isocenter, delivered with a TrueBeam LINAC, under mask immobilization, Novalis couch positioning, and ExacTrac X-ray and infrared positioning and motion monitoring. Treatment response, intensity and frequency of pain, presence of recurrence, and adverse effects were analyzed. Results: A total of 91% of patients responded to treatment, with a median latency of 15 days (interquartile range [IQR], 41). Nine patients (22%) experienced minor recurrence at a median time of 7 months (IQR, 3), and 14 patients (34%) experienced a major recurrence at a median time of 12 months (IQR, 19). After recurrence, both frequency and intensity of episodes remained significantly lower than pretreatment. At last follow-up, response was maintained in 25 patients (60%). No radiosurgery-related severe morbidity or mortality was found. Conclusions: Mask-based immobilization combined with image-guided radiation delivered by rotating gantry-based LINAC system provides a safe and effective radiosurgical treatment for TN, which is indicated for drug-resistant idiopathic or secondary TN patients and for drug-resistant classical TN patients who are not candidates for microvascular decompression.
Pseudo-senescence induced by palbociclib does not sensitise pleural mesothelioma cells to combinations with senolytics
(Nature Publishing Group, 2026-04-10) Sreeram, Iswarya; Plans Marín, Sílvia; Cruz-Rodríguez, Mabel; Aliagas Marín, Elisabeth; Palau Gallinat, Didac; Muñoz Pinedo, Cristina; Nadal, Ernest
Pleural Mesothelioma (PM) is an aggressive neoplasm of the lung pleura with poor survival rates, highlighting the urgent need for novel therapeutic options. The CDK4/6 inhibitors abemaciclib and palbociclib have demonstrated promising results in patient-derived xenograft models of PM. In this study, we observed that palbociclib reduced proliferation, leading to increased cell size, enhanced SA-β-galactosidase activity, and elevated secretion of IL-6 and IL-8 (SASP), all of which are hallmarks of senescence. However, upon drug removal, the cells regrew. To enhance therapeutic efficacy, we attempted to induce cell death in palbociclib-pretreated PM cells with conventional senolytics, such as BH3 mimetics. While some cells showed sensitivity to Bcl-xL inhibitors, neither navitoclax nor the specific Bcl-xL inhibitor A-1331852, nor other BH3 mimetics targeting Bcl-2 (venetoclax) or Mcl-1 (S63845) increased cell death when combined with palbociclib. We explored the activity of signalling pathways after treatment with palbociclib and identified higher Src and STAT3 phosphorylation, as well as activation of the mTORC1 axis. Therefore, we employed inhibitors of these pathways, such as dasatinib, momelotinib or Torin-1, which did not synergise with palbociclib to kill the cells. In contrast, we found that the chemotherapeutic drug cisplatin induces permanent cell cycle arrest and complete senescence in PM cells. While both drugs increased the phosphorylation of γH2AX, the effects of cisplatin were stronger and more consistent across cell lines. The differential effects of palbociclib and cisplatin on permanent growth arrest were verified by sorting PM cells based on size and β-galactosidase activity. Our findings underscore the importance of understanding the nature of therapy-induced senescence when assessing the effectiveness of senolytics in different tumour models.
Evaluated Childhood Obesity Prevention and Management Programs in Europe, 2015–2024: A Structured Narrative Review of Behavioral and Anthropometric Outcomes
(MDPI, 2026-03-30) Wójcik, Małgorzata; Kozioł Kozakowska, Agnieszka; Iwańska, Anna; Cichocka Mroczek, Ewelina; Łuszczki, Edyta; Wyszyńska, Justyna; Baran, Ewa; González Ramos, Laura; Hartgring, Isa; Martínez, Lola; Parnarauskienė, Justė; Fernández Aranda, Fernando; Jankauskiene, Augustina; Drożdż, Dorota; Mazur, Artur; Álvarez Pitti, Julio
Background: This structured narrative review summarizes and critically appraises evaluated childhood obesity prevention programs implemented in European countries and published between 2015 and 2024. Methods: Systematic searches for PubMed, EBSCOhost, and Google Scholar, complemented by research registries, were conducted year-by-year and independently screened by two reviewers. Results: Five multinational/international programs were identified alongside multiple national initiatives delivered in family, school, community, healthcare, and digital settings. Overall, interventions consistently improved intermediate outcomes—such as selected dietary behaviors, physical activity participation, knowledge, and parental self-efficacy—more than anthropometric endpoints. Effects on BMI/BMI z-score or overweight/obesity prevalence were heterogeneous and frequently small or non-significant, especially for short-duration, single-setting educational interventions. More favorable anthropometric outcomes were commonly reported in long-term, population-scaled physical activity or community-based programs as well as in multidisciplinary healthcare-supported approaches; however, these strategies were typically resource-intensive and sometimes showed differential effectiveness across socioeconomic or cultural groups. Conclusions: The evidence indicates that single-setting or short-term interventions may improve selected behavioral outcomes but are generally insufficient to produce sustained effects on anthropometric measures without integration into broader, multi-level strategies. It is needed to integrate families, schools, communities, and health services with explicit attention to sustainability and equity. Technology-supported tools may strengthen reach and continuity when embedded within comprehensive prevention frameworks.
Common practice elements of cognitive behavioral therapy for gaming disorder: A systematic review and expert panel evaluation
(Elsevier Ltd., 2026-06) Radunz, Marcela; Stevens, Matthew W.R.; Behm, Sanni; Hameed, Muddsar; Bowden Jones, Henrietta; Delfabbro, Paul; Demetrovics, Zsolt; Higuchi, Susumu; Potenza, Marc N.; Wölfling, Klaus; Brandhorst, Isabel; Bore, Per; Claesdotter Knutsson, Emma; González Bueso, Ma. Vega; Herpertz, Stephan; Dieris-Hirche, Jan; Hofstedt, Annika; Gordh, Anna Söderpalm; Jimenez Murcia, Susana; Nielsen, Philip; Pallesen, Ståle; Paschke, Kerstin; Ratta-apha, Woraphat; Rigter, Henk; Santamaria, Juan José; Sugara, Gian Sugiana; King, Daniel L.
Gaming disorder (GD) is an addictive disorder with health and social impacts recognized by the World Health Organization. Although the GD treatment evidence base appear to favor cognitive behavioral therapy (CBT), knowledge of its common practice elements is limited. This systematic review critically evaluates CBT interventions for GD, encompassing individual, group, and mixed approaches, to identify and synthesize common practice elements. Employing a systematic review protocol following PRISMA guidelines and guided by an international expert panel, this review identified CBT studies and then critically reviewed their associated treatment manuals, guidelines, handouts, and related resources. A database search yielding 8479 results identified 28 studies from 12 countries reporting on 22 CBT interventions (n = 7 individual; n = 7 group; n = 8 mixed). Study authors were invited to share intervention materials, which were then independently coded and synthesized. Overall, 14 common practice elements were identified. The most frequent element was emotion regulation skills training (n = 21; 95.5%), followed by psychoeducation (n = 20; 90.9%) and cognitive restructuring (n = 19; 86.4%). Exposure techniques, and strength identification and self-compassion were the least frequent (n = 6; 27.3%). All individual CBT interventions used behavioral activation, psychoeducation, and relapse prevention, whereas emotion regulation skills training was the most frequently used element in group CBT. These findings reveal commonly reported CBT practice elements in the GD evidence base and provide expert summaries of established and less utilized therapeutic techniques. Improving the field's shared understanding of CBT is foundational to advancing GD clinical research and a model of best practice.
The endonuclease MCPIP1 protects against liver cancer development in a sex-dependent manner by modulating β-catenin and CREB1
(Elsevier, 2026-05) Kwapisz, Oliwia; Marona, Paulina; Gorka, Judyta; Myrczek, Rafał; González Sánchez, Ester; Bertran Rodríguez, Esther; Kotlinowski, Jerzy; Głuc, Maciej; Alay, Ania; Pydyn, Natalia; Kujdowicz, Monika; Ramos, Emilio; Fabregat Romero, Isabel; Miekus, Katarzyna
Background & Aims: Monocyte chemoattractant protein-induced protein 1 (MCPIP1), encoded by ZC3H12A, is a negative regulator of inflammation and tumorigenesis. While its role has been implicated in various cancers, the function of MCPIP1 in hepatocellular carcinoma (HCC) remains poorly understood. This study explored the contribution of hepatocyte-specific MCPIP1 loss to HCC pathogenesis, highlighting its role in overcoming the inherent tumor resistance observed in female mice. Methods: Liver tissues (n ≥5 per group) and primary hepatocytes (n ≥3 per group) were evaluated using western blotting, immunohistochemistry, immunofluorescence, RNA sequencing and pathway-enrichment analysis. The expression levels of MCPIP1 in HCC were measured by quantitative reverse-transcription PCR. The results are presented as mean ± SD, Student's t or Mann‒Whitney U tests were used for statistical analysis of two groups. For more than two groups, ordinary two-way ANOVA was used. Results: The hepatocyte-specific loss of MCPIP1 markedly promoted fibrosis and tumorigenesis, particularly in female mice, disrupting the normal sex-related protection observed in the diethylnitrosamine model. As determined by next-generation sequencing and bioinformatics analysis, oncogenic and fibrotic programs, including the EMT, Wnt/β-catenin, and JAK/STAT3 pathways, were activated in MCPIP1 knockout livers. These molecular events activated β-catenin, c-Met, and IL-6/STAT3/NF-κB signaling, and they enhanced fibrotic remodeling. In MCPIP1-deficient hepatocytes, active β-catenin and CREB1 accumulated in the nucleus, and the expression of protumorigenic targets, such as Spp1, Tgfb2, and Adam17 increased. Moreover, MCPIP1 expression was significantly downregulated in human HCC tissues and correlated with tumor progression. Conclusions: MCPIP1 plays a protective role against inflammation-driven hepatocarcinogenesis, particularly in females, by restraining fibrotic remodeling and oncogenic signaling. The downregulation of MCPIP1 expression promotes a tumor-promoting microenvironment through the coordinated activation of the β-catenin, STAT3, and CREB1 pathways. Impact and implications: This study identifies MCPIP1 as a tumor suppressor in inflammation-driven hepatocarcinogenesis and reveals its role in maintaining tumor resistance, particularly in females. These findings link MCPIP1 loss to the activation of oncogenic and fibrotic signaling pathways, offering new insight into sex differences in HCC susceptibility and highlighting its potential as a biomarker of disease progression.
Urinary polyphenol signature of the Mediterranean diet is associated with lower cardiovascular disease risk: the PREDIMED trial
(BioMed Central, 2026-12-01) Domínguez López, Inés; Galkina, Polina; Fernández-Duval, Gonzalo; Pozzoli, Carola; Razquin, Cristina; Jáuregui Pallarés, Olga; Salas Salvadó, Jordi; Tojal Sierra, Lucas; Fitó Colomer, Montserrat; Corella Piquer, Dolores; Fiol Sala, Miguel; Lapetra, José; Gómez Gracia, Enrique; Pintó Sala, Xavier; Ruiz-Canela, Miguel; Castañer Niño, Olga; Liang, Liming; Sun, Qi; Serra Majem, Lluís; Ros Rahola, Emilio; Martínez-González, Miguel Ángel, 1957-; Estruch Riba, Ramon; Hu, Frank B.; Lamuela Raventós, Rosa Ma.
The Mediterranean diet (MedDiet) is strongly associated with lower cardiovascular disease (CVD) risk and is particularly rich in polyphenols, bioactive compounds with potential cardioprotective effects. However, the specific phenolic compounds underlying these benefits remain unclear. The objective of this study was to develop a urinary multi-metabolite signature of phenolic compounds reflecting MedDiet adherence and to evaluate its prospective association with CVD risk. Methods. In a case–cohort nested study within the PREDIMED trial, we measured 62 phenolic metabolites in spot urine by liquid chromatography–high‐resolution mass spectrometry at baseline and after 1 year in 1180 individuals: 653 incident CVD cases (stroke, myocardial infarction, CVD death, or heart failure) and a random subcohort of 603 participants (76 overlapping cases). We applied elastic net regression to derive a urinary multi-metabolite signature prospectively associated with MedDiet adherence, measured by the validated 14-item Mediterranean Diet Adherence Screener (MEDAS). Multivariable Cox models were used to estimate hazard ratios (HRs) of CVD by levels of the multi-metabolite signature. Results. The urinary multi-metabolite signature, comprising eight phenolic compounds selected by elastic net regression, was inversely associated with CVD risk in a dose–response pattern (HR per SD = 0.80 (0.68–0.94); HR Q4 vs Q1 = 0.48 (0.30–0.78); <em>p</em>-trend = 0.002). The metabolites included in the signature were derived from foods typical of the MedDiet, particularly virgin olive oil, wine, nuts, fruits, and vegetables. After 1 year, MedDiet interventions significantly increased urolithin A metabolites (derived from walnuts) compared to the control group. Conclusions. We identified a urinary multi-metabolite signature of MedDiet adherence that is prospectively associated with lower CVD incidence. These findings support that polyphenols derived from the MedDiet showed inverse associations with cardiovascular outcomes. Trial registration. The study was registered with the International Standard Randomized Controlled Trial Number (ISRCTN) 35739639.
Antagonistic SMAD2/3 control of TIMP-1, VEGF-A, and hypoxia signaling in myofibroblasts shapes histotype-specific angiogenesis in lung cancer
(Nature Publishing Group, 2026-03-30) Díaz Valdivia, Natalia; Duch, Paula; Ikemori, Rafael; Parker, Amelia L.; Arshakyan, Marselina; Llorente, Alejandro; Bernardo, Alejandro; Rodríguez Rojas, José; Carrasco Jordan, Josep Lluís; Park, Danielle; Sahai, Erik; Fillat i Fonts, Cristina; Juan, Manel; Nadal, Ernest; Reguart, Noemí; Radisky, Derek C; Casanovas, Oriol; Alcaraz,Jordi
Non-small cell lung cancer (NSCLC) exhibits disparate responses to anti-angiogenic therapies between its two major histologic subtypes, lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC), suggesting a histotype-dependent angiogenesis regulation. Tumor-associated fibroblasts (TAFs) exhibit an activated/myofibroblast-like phenotype in NSCLC, and are emerging as major regulators of tumor progression; yet, their role in controlling angiogenesis in NSCLC remains undefined. Here we analyzed angiogenesis/hypoxia markers in NSCLC, and combined transcriptomics (bulk RNA-seq, scRNA-seq), angiogenesis arrays, genetic perturbations and functional in vitro and in vivo assays to dissect the histotype-dependent production of pro-angiogenic factors in TAFs. We observed greater angiogenesis and reduced necrosis/hypoxia in LUAD compared to LUSC across multiple patient cohorts. The LUAD-TAF secretome was primed for angiogenesis through SMAD3-dependent overproduction of key regulators, particularly TIMP-1 and VEGF-A. We also uncovered a novel function for TIMP-1 in promoting endothelial cell hyperbranching over basal VEGF signaling. Conversely, LUSC-TAFs displayed diminished angiogenic effects despite upregulating HIF-1α and a hypoxia-associated transcriptional signature, owing to their lower SMAD3 and compensatory increase in SMAD2. Our study unveils the critical influence of TAFs in shaping the distinct angiogenic landscapes in LUAD and LUSC through the opposing SMAD2/3 regulation of TIMP-1, VEGF-A and hypoxia signaling. These results also highlight the therapeutic potential of targeting stromal SMAD3/TIMP-1 in LUAD or microenvironmental stressors such as hypoxia and acidosis in LUSC. In addition, these findings provide a biological framework for understanding the histotype-dependent patterns of dissemination, immune evasion, and response to anti-angiogenic therapies in NSCLC.
Latin-American Ambulatory Blood Pressure Registry (MAPA-LATAM): An urgent need Registro Latinoamericano de monitorización ambulatoria de la presión arterial (MAPA-LATAM): una necesidad urgente
(Elsevier, 2021-11-01) Camafort Babkowski, Miguel; Alcocer, L.; Coca, Antonio; Lopez-Lopez, J.P.; López-Jaramillo, P.; Ponte-Negretti, C.I.; Sebba-Barroso, W.; Valdéz, O.; Wyss, F.
La hipertensión arterial (HTA) es el principal factor de riesgo de enfermedad cardiovascular. Aunque es un problema global, independiente de la situación económica, región, raza o cultura, los datos disponibles con respecto a Latinoamérica no son muy abundantes. Por otra parte, las guías clínicas enfatizan la importancia de obtener lecturas fiables de la presión arterial. Por ello, se recomienda el uso de la monitorización ambulatoria de la presión arterial (MAPA), que mejora su precisión y reproducibilidad, ayudando a un mejor diagnóstico, en la toma de decisiones terapéuticas, y representa una mejor estimación pronóstica que las medidas en consulta. Lamentablemente, no existe ningún registro prospectivo global de MAPA para toda Latinoamérica que analice la prevalencia de HTA, el grado de su conocimiento, su porcentaje de tratamiento y el grado de control. En consecuencia, los autores de este artículo consideran prioritaria su puesta en marcha.
Problematic usage of the internet: A policy map of the use of internet and its possible mental health consequences in adolescents across United Kingdom, France, Germany, Italy, Australia, Canada, the United States, and New Zealand
(Elsevier B.V., 2026-06) Snegg, Julia; Larrain, Blanca; Mosler, Kristin; Van Kessel, Robin; Achab, Sophia; Corazza, Ornella; Penazzi, Gabriele; Stein, Dan J., 1962-; Ekhtari, Hamed; Bowden Jones, Henrietta; Ioannidis, Konstantinos; Barbati, Vittoria; Demetrovics, Zsolt; Chamberlain, Samuel R.; Carmi, Lior; Zohar, Joseph; Rumpf, Hans‐Jürgen; Hall, Natalie; Menchón Magriñá, José Manuel; Sales, Célia M. D.; Montag, Christian; Lindenberg, Katajun; Susi, Mart; Huizink, Anja; Potenza, Marc N.; Pallanti, Stefano; Morgan, Nick; Moreno, Carmen; Purper-Ouakil, D.; Brand, Matthias; Yücel, Murat; Czakó, Andrea; Walitza, Susanne; Burkauskas, Julius; Felvinczi, Katalin; Smith, Megan; Wellsted, David; Jones, Julia; Dias, Teresa Silva; Foster, Simon; Mohler Kuo, Meichum; Neumann, Ina; Fongaro, Erica; Fally, Sara; Oliveira, Hernani; Abregú Crespo, Renzo; Sepúlveda Palomo, Marta; Fineberg, Naomi A.; Roman-Urrestarazu, Andrés
This work analyses policies related to the Problematic Usage of the Internet (PUI) and its relationships to adolescent mental health across the United Kingdom, France, Germany, Italy, Australia, Canada, the United States, and New Zealand. Using a policy path dependency framework, national legislation was examined to assess relationships with PUI. The study maps policy by reviewing governmental legislation and databases, analysing them on macro (societal), meso (market/intermediary organisations), and micro (citizen rights, duties, and protection) levels. It explores legal instruments related to PUI, including data protection, cybersecurity, content regulation, and harassment, offering both historical and comparative analyses across the eight countries. Findings indicate that while several countries have policies indirectly regulating PUI, significant legislative gaps persist relating to adolescent mental health. Most policies address broader internet concerns without specifically targeting PUI or its effects on mental health. Overall, the analysis highlights the need for more targeted public health policies to address the root causes of PUI, advocating for tailored interventions focused on adolescent well-being.
Immunomodulatory therapy, risk factors and outcomes of hospital-acquired bloodstream infection in patients with severe COVID-19 pneumonia: a Spanish case-control matched multicenter study (BACTCOVID)
(European Society of Clinical Microbiology and Infectious Diseases, 2021-07-07) Abelenda Alonso, Gabriela; Rombauts, Alexander; Gudiol González, Carlota; Oriol, Isabel; Simonetti, Antonella Francesca; Coloma Conde, Ana; Rodríguez-Molinero, Alejandro; Izquierdo, Elisenda; Díaz Brito, Vicens; Sanmartí Vilamala, Montserrat; Padullés Zamora, Ariadna; Grau, Inmaculada; Ras, Mar; Bergas, Alba; Guillem, Lluïsa; Blanco Arévalo, Alejandro; Alvarez-Pouso, Claudia; Pallarès, Natàlia; Videla, Sebastià; Tebé, Cristian; Carratalà, Jordi
Objectives The effect of the use of immunomodulatory drugs on the risk of developing hospital-acquired bloodstream infection (BSI) in patients with COVID-19 has not been specifically assessed. We aim to identify risk factors for, and outcomes of, BSI among hospitalized patients with severe COVID-19 pneumonia. Methods We performed a severity matched case–control study (1:1 ratio) nested in a large multicentre prospective cohort of hospitalized adults with COVID-19. Cases with BSI were identified from the cohort database. Controls were matched for age, sex and acute respiratory distress syndrome. A Cox proportional hazard ratio model was performed. Results Of 2005 patients, 100 (4.98%) presented 142 episodes of BSI, mainly caused by coagulase-negative staphylococci, Enterococcus faecalis and Pseudomonas aeruginosa. Polymicrobial infection accounted for 23 episodes. The median time from admission to the first episode of BSI was 15 days (IQR 9–20), and the most frequent source was catheter-related infection. The characteristics of patients with and without BSI were similar, including the use of tocilizumab, corticosteroids, and combinations. In the multivariate analysis, the use of these immunomodulatory drugs was not associated with an increased risk of BSI. A Cox proportional hazard ratio (HR) model showed that after adjusting for the time factor, BSI was associated with a higher in-hospital mortality risk (HR 2.59; 1.65–4.07; p < 0.001). Discussion Hospital-acquired BSI in patients with severe COVID-19 pneumonia was uncommon and the use of immunomodulatory drugs was not associated with its development. When adjusting for the time factor, BSI was associated with a higher mortality risk.
Mapping policies related to problematic usage of the internet in seven European countries: Netherlands, Spain, Hungary, Lithuania, Portugal, Estonia and Switzerland
(Elsevier B.V., 2026-06) Larrain, Blanca; Van Kessel, Robin; Mosler, Kristin; Penazzi, Gabriele; Corazza, Ornella; Achab, Sophia; Stein, Dan J., 1962-; Ekhtari, Hamed; Bowden Jones, Henrietta; Ioannidis, Konstantinos; Barbati, Vittoria; Demetrovics, Zsolt; Chamberlain, Samuel R.; Carmi, Lior; Zohar, Joseph; Rumpf, Hans‐Jürgen; Hall, Natalie; Menchón Magriñá, José Manuel; Sales, Célia M. D.; Montag, Christian; Lindenberg, Katajun; Susi, Mart; Huizink, Anja; Potenza, Marc N.; Pallanti, Stefano; Morgan, Nick; Moreno, Carmen; Purper-Ouakil, D.; Brand, Matthias; Yücel, Murat; Czakó, Andrea; Walitza, Susanne; Burkauskas, Julius; Felvinczi, Katalin; Smith, Megan; Wellsted, David; Jones, Julia; Dias, Teresa Silva; Foster, Simon; Mohler Kuo, Meichum; Neumann, Ina; Fongaro, Erica; Fally, Sara; Oliveira, Hernani; Abregú Crespo, Renzo; Sepúlveda Palomo, Marta; Fineberg, Naomi A.; Roman-Urrestarazu, Andrés
This work presents a policy analysis regarding Problematic Usage of the Internet (PUI) across seven countries (Netherlands, Spain, Hungary, Lithuania, Portugal, Estonia, and Switzerland) belonging to or associated with the European Union (EU). I It examines legislative instruments addressing PUI and its multifaceted impacts on society, including social, economic, and political dimensions. Despite the growing prevalence of PUI, particularly among adolescents, and its association with various mental health concerns, the study reveals a notable gap in direct policy interventions targeting PUI within these countries. Existing regulations largely focus on broader digital governance issues like data protection, cybersecurity, and market regulation, offering only indirect approaches to mitigating PUI's adverse effects. Our findings highlight a pressing need for innovative policy frameworks that incorporate mental health considerations into digital governance, promoting a balanced approach that fosters market innovation while ensuring robust public health protections. Building on the policy discourse examined in this study, future research should focus on developing targeted, multidimensional strategies to mitigate the risks associated with problematic internet use (PUI), with particular emphasis on safeguarding the well-being of vulnerable populations.
Dupilumab-induced eosinophilia in severe asthma: 2-year follow-up real-life evidence from biologic naïve and previously treated patients
(Elsevier B.V., 2026-06) Bellver Asperilla, Cristina; Muñoz Esquerre, Mariana; Romero-Ortiz, Ana Maria; Cabrerizo-Carreño, Héctor; Orozco Echeverría, Sandra; Gonzalez Compta, Francesc Xavier; Golet Fors, Mireia; Andújar Ruiz, Alexandra; Suárez Cuartín, Guillermo Rafael; Padullés Zamora, Núria; Ardanuy Tisaire, María Carmen; Santos Pérez, Salud
Data from real-life settings regarding dupilumab-associated eosinophilia remains limited, particularly concerning potential risk factors for developing hypereosinophilia after treatment initiation. Methods. We conducted a prospective observational study including an initial cohort of 36 patients with severe asthma treated with dupilumab and followed for up to two years. Blood eosinophil count (BEC), asthma outcomes, and treatment response — including ACT score, lung function, exacerbations, oral corticosteroid use, and the EXACTO scale as a multidimensional response measure — were assessed at baseline and at weeks 24, 52, and 104. Eosinophilia was categorized as mild (>500 cells/μL), moderate (>1500 cells/μL), or severe (>5000 cells/μL), and hypereosinophilia as moderate-severe eosinophilia. Results. Transient eosinophilia occurred in 47.2% of patients and transient hypereosinophilia in 19.4%, with most cases being asymptomatic. Two patients (5.6%) developed a clinical presentation suggestive of eosinophilic granulomatosis with polyangiitis (EGPA). Hypereosinophilia was more frequent among patients who had switched from prior anti–IL-5/IL-5R therapy. Among the cases that developed hypereosinophilia, 42.9% persisted at the 2-year follow-up, whereas mild eosinophilia persisted in 65% of patients. Nevertheless, dupilumab treatment resulted in significant improvements in asthma control and treatment response outcomes, irrespective of eosinophil levels or prior biologic exposure. Conclusion. Eosinophilia is a common finding in patients receiving dupilumab, generally without significant safety implications. The use of dupilumab is safe and highly effective, even in patients previously treated with anti–IL-5/IL-5R biologics. However, rare cases of severe eosinophilic complications may occur, making long-term systematic monitoring advisable.

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