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Letter to the editor:Diastolic dysfunction as predictive parameter for the development of post-TIPS cardiac decompensation
No full textRevascularisation strategies for non-acute myocardial ischaemic syndromes
No full textBackground Contemporary guidelines by the European Society for Cardiology and American College of Cardiology/American Heart Association for the treatment of non-acute myocardial ischaemic syndromes dispute the value of revascularisation and differ in their recommendation to perform revascularisation. A Bayesian network meta-analysis was performed, evaluating the strength of evidence for the comparative incremental effectiveness of coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) over medical therapy on long-term outcomes. Methods A hierarchical Bayesian network meta-analysis was designed (PROSPERO CRD42024541215, date 20 May 2024), including randomised controlled trials (RCTs) published between 2005 and 10 June 2025, which consisted of three initial treatment modalities: optimal medical therapy (OMT), PCI+OMT and CABG+OMT. The primary outcome was all-cause mortality at maximum follow-up; secondary outcomes were trates of the rates of myocardial infarction, stroke and re-revascularisation at maximum follow-up, expressed in HRs and 95% credible intervals (CrIs), accompanied by surface under the cumulative ranking curve (SUCRA) scores. Results 10 RCTs, comprising 10 742 patients, were included. For all-cause mortality, the estimated median HR of CABG+OMT versus OMT was 0.84 (95% CrI 0.68–1.07); the HR of PCI+OMT versus OMT was 0.93 (0.79–1.16); and the HR of CABG+OMT versus PCI+OMT was 0.91 (0.71–1.13). The SUCRAs of a CABG+OMT strategy ranking as the optimal revascularisation treatment regarding mortality, myocardial infarction, stroke and re-revascularisation were 88.1%, 99.7%, 17.5% and 99.5%, respectively. Results were consistent across sensitivity analyses, including in the node-splitting models. Conclusions This Bayesian network meta-analysis found that an initial CABG (+OMT) revascularisation strategy was associated with higher probabilities of optimal outcomes, with the exception of stroke, compared with an initial PCI (+OMT) revascularisation strategy, although CrIs overlapped, suggesting that some uncertainty remains.</p
Oncological Outcomes of Locally Recurrent Rectal Cancer Treated With Curative Intent:A Single Center Retrospective Cohort Study
No full textBackground: Treatment paradigms for patients with locally recurrent rectal cancer (LRRC) have shifted from palliative approaches to multimodal curative-intent treatment in selected patients. This retrospective cohort study evaluates survival outcomes following curative-intent treatment in patients with LRRC. Methods: All consecutive patients with LRRC undergoing curative-intent treatment at a tertiary referral center between 2014 and 2024 were retrospectively analyzed (n = 147). Overall survival (OS), local re-recurrence-free survival (LRFS), metastasis-free survival (MFS), and prognostic factors were analyzed using Kaplan–Meier and Cox regression analyses. Results: 147 patients underwent neoadjuvant treatment with curative intent at baseline. After response assessment, 117/147 (80%) patients continued curative therapy, which consisted of 109/117 (93%) patients undergoing surgery and a highly selected group of 8/117 (7%) patients monitored with a watch-and-wait strategy. For the remaining 30/147 patients (20%), treatment intent changed from curative to palliative. Median OS was 54 months with a 5-year OS of 47%. For patients treated with an overall curative intent (n = 117), median OS was 63 months with a 5-year OS of 58%. Clear resection margins, achieved in 76% of surgical cases, was a prognostic factor for OS and LRFS: 5-year OS was 66% for R0-resections and 33% for R1-resections (p < 0.001), and 3-year RFS was 69% for R0-resections and 50% for R1-resections (p < 0.001). Among the watch-and-wait group, 5/8 patients remained alive and disease-free (median follow-up 14 months (IQR 9–16)). Conclusions: This single-center retrospective cohort study demonstrates reasonably good oncological outcomes following curative-intent LRRC treatment. Further investigation of watch-and-wait strategies in highly selected patients is warranted.</p
Learning asymmetry as a predictor of mood and behavior dynamics:A network analysis
No full textWhile studying appetitive and aversive conditioning is common in psychopathology research, studies that measure both types of learning simultaneously are rare. To gain insight into the role of appetitive and aversive learning in the complex interaction of positive mood, negative mood, worry, craving, avoidance and impulsive behavior, this study used a relative measure of the strength of appetitive versus aversive learning – the learning asymmetry – as a predictor of network dynamics of mood states and behavior. 100 healthy volunteers performed an appetitive and aversive conditioning task and completed an ecological momentary assessment study, where they were surveyed six times per day for 21 days. Groups were defined based on higher sensitivity to appetitive learning (positive learning asymmetry) or aversive learning (negative learning asymmetry). The positive asymmetry group was hypothesized to be more sensitive to positive mood changes, and the negative asymmetry group was hypothesized to be more sensitive to negative mood changes. Contrary to our hypothesis, results show that impulsive behavior was more likely to follow negative mood, specifically anger, in the positive but not the negative asymmetry group. These results demonstrate the potential for network analysis to elucidate complex interactions between mood and behavior associated with individual differences in learning
Quantitative systems toxicology:modelling to mechanistically understand and predict drug safety
No full textReliable prediction and prevention of adverse drug reactions (ADRs) remains a key challenge in the development of new medicines. Advanced mathematical and computational modelling approaches, which incorporate cutting-edge mechanistic understanding of ADRs in concert with systematically collected data addressing knowledge gaps, are integral components of model-informed drug discovery and development (MID3). These approaches provide a precise, quantitative framework for predicting and mitigating safety risks in the earliest phases of drug development. Here, we highlight recent developments in the burgeoning field of quantitative systems toxicology (QST), including insights into the current state-of-the-art, as well as outcomes from the Innovative Medicines Initiative (IMI) 2 TransQST project. QST models that describe the disruption of cardiovascular, gastrointestinal, hepatic and renal physiological functions following drug exposure are presented, along with recommendations for their application in drug discovery and development
Linking Transparency and Accountability: Analysing The Connection Between TikTok's Terms of Service and Moderation Decisions
No full textThe European Commission's Digital Services Act (DSA) mandates that Very Large Online Platforms (VLOPs), like TikTok, provide Statements of Reason (SoRs) to justify their content moderation decisions in an attempt to enhance transparency and accountability for these platforms. However, we can often notice a gap between these automated decisions and the platform's written policies. This leaves users unable to understand the specific rule they have violated. This paper addresses this gap by developing and evaluating a pipeline to link TikTok's SoRs from the DSA transparency database to the most relevant clause from TikTok's policy documents. We test multiple methods to perform the linking task and evaluate performance using a wide range of retrieval methods and metrics.We develop and deliver a gold-standard dataset where a team of legal research assistants annotated 100 SoRs based on four criteria: clarity, understanding, presence of unclear terms and level of detail, each rated on a 1--4 scale. In addition, a binary rating is assigned for redress clarity. Moreover, annotators determined the best link to the relevant TikTok policy clauses. Results show that both TikTok's SoRs and policy clauses are often extremely broad, granting TikTok more freedom to decide how to apply the clauses, making it even less transparent for users. We also provide a demo that, for each SoR, provides a ranking of the most relevant clauses from TikTok's written policies, a tool that can be useful for users, regulators and researchers to better understand content moderation decisions, assess compliance with transparency requirements, and support further analysis of platform accountability
Adult ependymoma:results from the Dutch Brain Tumour Registry on primary treatment and survival
No full textPurpose: Ependymomas are rare tumours of the central nervous system (CNS). This study reports real-world data regarding primary treatment and outcome for adult patients diagnosed in the Netherlands between 2014 and 2023. Methods: Diagnostic and treatment data on adult patients with a newly diagnosed ependymoma were obtained from the Dutch Brain Tumour Registry. Factors associated with incomplete resection and adjuvant radiotherapy (RT) were identified using logistic regression analyses, thereby accounting for variation between CNS regional tumour boards through mixed-effect modelling when relevant. In case of variation, case-mix adjusted ratios of tumour boards were evaluated in funnel plots. Prognostic factors for overall survival (OS) at 5 years were assessed with the Kaplan-Meier method and Cox proportional hazards regression models. Analyses were performed on multiple imputed datasets (m = 10) to account for missing data. Results: Among 575 patients, 74 (12.9%) ependymomas were located in the supratentorial region, 129 (22.5%) in the posterior fossa, and 370 (64.6%) in the spine. Incomplete resection occurred more often in posterior fossa, and in larger and metastatic/multifocal ependymomas. Adjuvant RT was administered to 47 of 173 patients with a metastatic/multifocal and/or incompletely removed WHO grade 1–2 tumour (27.2%), and to 26 of 34 patients with a WHO grade 3 ependymoma (76.5%). Adjuvant RT conferred significant survival benefit (hazard ratio 0.17, 95% confidence interval 0.06–0.53, p < 0.01) following adjustment for other factors. Conclusion: This study substantiates the benefit of adjuvant RT for selected adult patients with an ependymoma and emphasizes the need for more coordinated management across tumour boards.</p
Placental gene expression of the AMPK signaling pathway in association with gestational exposure to ambient air pollution
No full textObjective: Prenatal ambient air pollution exposure is able to reach the fetus by crossing the placenta, a highly metabolically active organ. The adenosine monophosphate-activated protein kinase (AMPK) signaling pathway is a crucial regulator of the placental cellular metabolism, necessary for normal placental and fetal development. This study investigates the association between in utero exposure to BC, NO2, and PM2.5, and differences in placental gene expression of the AMPK signaling pathway at birth. Material and methods: Transcription data from 182 placentas of the ENVIRONAGE birth cohort were obtained through microarray analysis. Exposure levels were estimated using a spatio-temporal model for the mothers' residential address during pregnancy. The associations between transcription levels of 76 genes, clustered by the cascades of the AMPK signaling pathway, and the air pollution exposures during different time windows of pregnancy were analyzed using a mixed-effects model adjusting for potential confounders. Results: Higher prenatal levels of BC, NO2, and PM2.5 were associated with downregulated gene expression of the central AMPK gene cluster and multiple upstream and downstream cascades of the AMPK signaling pathway. In a multi-pollutant model, the observed patterns of downregulation remained, supporting the robustness of the associations when considering co-exposure to different air pollutants. Conclusion: This study provides new insights into the possible adverse effects of ambient air pollution exposure on placental development, affecting the placental metabolism at the transcript level. Whether reduced placental AMPK signaling may play a role in air pollution-induced birth outcomes and their long-term consequences needs to be further addressed
