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Long-read DNA and RNA sequencing reveal an intronic retrotransposon insertion in TCOF1 causing Treacher Collins syndrome
No full textTreacher Collins syndrome (TCS) is a craniofacial genetic disorder caused by loss-of-function variants in TCOF1 , POLR1B , POLR1C , or POLR1D . Here, we describe two previously undiagnosed paternal half-siblings affected with clinical TCS, and their apparently unaffected father. Diagnostic short-read RNA sequencing) identified aberrant expression of TCOF1 and optical genome mapping detected a large genomic insertion therein. Long-read genome sequencing (lrGS) resolved a deep intronic 3.5 kb SINE-VNTR-Alu (SVA) retrotransposon insertion in intron 17 of TCOF1 . Long-read RNA sequencing (lrRNA-seq) demonstrated that the insertion was partially exonized inducing isoform switch to the shorter non-canonical TCOF1 isoform c. SVA insertion was confirmed in both half-siblings, and we detected mosaicism in the father. This work demonstrates the potential of lrRNA-seq and lrGS, to identify pathogenic variants in unexplained genetic disorders.</p
Revisiting health state preferences after 20 years:A new EQ-5D-3L value set for the Netherlands
No full textIntroduction: Value sets for the EQ-5D-3L have been developed since the 1990’s, using methods that are now considered outdated. The Dutch EQ-5D-3L value set was developed using data collected in 2003, and population’s preferences may have shifted over time. Consequently, the existing value set may no longer accurately represent the preferences of the Dutch general population. This study aims to develop a new EQ-5D-3L value set using state-of-the-art methods and compare it with the existing value set. Methods: A nationally representative sample of 417 Dutch adults, stratified by age and sex, completed 12 composite time trade-off (cTTO) tasks via online EuroQol Valuation Technology interviews. The data were modelled using a Tobit model that accounts for heteroskedasticity and the censored nature of cTTO data. Agreement between the new and existing value set was assessed using Bland-Altman and scatter plots. Results: Pain/discomfort and mobility were the most important dimensions in the new value set, whereas pain/discomfort and anxiety/depression were most important in the existing value set. The lowest health state value was − 0.723, considerably lower than the − 0.329 of the existing value set. The Bland-Altman and scatter plots indicated limited agreement between the two value sets. Conclusion: The new Dutch EQ-5D-3L value set differs substantially from the existing value set. We recommend its adoption and replacement of the previous value set. Our findings suggest that other countries with older value sets should consider similar updates to ensure accurate representation of contemporary societal preferences.</p
Editorial:TIPS in the Era of Aging and Metabolic Comorbidity—Rethinking Risks and Rewards. Authors Reply
No full textReply:From the authors of the ERS/ATS statement on the international multidisciplinary classification of the interstitial pneumonias
No full textImpact of Different Primary Treatment Strategies on Recurrence:Focused Treatment of Pancreatic Ductal Adenocarcinoma
No full textBackground: Increased application of neoadjuvant therapy (NAT) and adjuvant therapy (AT) could limit treatment options for pancreatic ductal adenocarcinoma (PDAC) recurrence. This study aimed to identify patterns of recurrence-focused treatment and survival following different primary treatment strategies. Methods: All patients who underwent PDAC resection in the Netherlands (2014–2019) were included. Patients were divided into five groups according to their primary treatment strategy: (1) resection only, (2) gemcitabine-based NAT + resection, (3) FOLFIRINOX-based NAT + resection, (4) resection + gemcitabine-based AT, and (5) resection + FOLFIRINOX-based AT. Differences in recurrence-focused treatment and post-recurrence survival (PRS) were assessed using multivariable logistic and Cox-proportional hazards analyses and were presented as odds ratios (ORs) and hazard ratios (HRs) with corresponding 95% confidence intervals (95% CIs), respectively. Results: In total, 1739 patients (median follow-up of 51 [interquartile range 34–64] months) were included, of whom 1272 (73%) had disease recurrence. In these patients, recurrence-focused treatment was administered in 64/124 (52%) after FOLFIRINOX-based NAT compared with 74/410 (18%) with resection only (OR 4.13 [95% CI 3.34–5.12]; P<0.001), 29/70 (41%) with gemcitabine-based NAT (OR 1.61 [95% CI 1.21–2.15]; P<0.001), 239/604 (39%) with gemcitabine-based AT (OR 1.73 [95% CI 1.43–2.09]; P<0.001), and 24/64 (38%) with FOLFIRINOX-based AT (OR 1.44 [95% CI 1.06–1.95]; P=0.02). Recurrence-focused treatment was associated with a median PRS of 11 (95% CI 10–13) months compared with 3 (95% CI 2–3) months in patients with best supportive care (HR 0.31 [95% CI 0.26–0.37]; P<0.001). Conclusions: Recurrence-focused treatment differs between patients with PDAC who received different primary treatment strategies and is associated with improved PRS.</p
APOBEC3B protein expression associates with poor prognosis for breast cancer patients with ER-positive disease
No full textAPOBEC enzymes, including APOBEC3B (A3B), have been linked to recurrent mutational patterns in breast cancers (BC). Currently, there is considerable level of evidence that A3B mRNA expression is associated with poor prognosis in ER-positive BC. Since the clinical relevance of A3B at the protein level has not been well studied, we evaluated A3B protein expression by immunohistochemistry on tumor tissue microarrays. Samples from 646 invasive, non-metastatic primary ER-positive BC patients who did not receive any systemic endocrine therapy as standard of care treatment, allowed us to study the pure prognostic impact of A3B protein expression on disease-free survival (DFS), metastatic disease-free survival (MFS), breast cancer specific-survival (BCSS), and overall survival (OS). Furthermore, 220 tumor specimens from BC patients who relapsed and did receive tamoxifen as first-line palliative treatment were included to study the association of A3B protein expression and progression free survival (PFS). Cox regression models were used to determine the impact of A3B protein expression on prognosis and PFS. We found that A3B expression associates with larger and higher grade tumors. Furthermore, univariable analyses showed that high A3B expression was associates with a shorter DFS (HR = 1.68; 95%CI = 1.31–2.14), MFS (HR = 1.93; 95%CI = 1.45–2.56), BCSS (HR = 2.72; 95%CI = 1.89–3.90), and OS (HR = 1.89; 95%CI = 1.40–2.56). Also, a shorter PFS (HR = 1.41; 95%CI = 1.03–1.92) was found. After adjustment for confounders, the observed associations remained significant. To conclude, in ER-positive BC, A3B protein expression is a marker for poor disease outcome and for rapid progression during endocrine treatment.</p
Response to ‘Towards an individualized strategy in perioperative chemotherapy for pancreatic cancer’
No full textIncidence and management of first metatarsophalangeal joint osteoarthritis in Dutch general practice estimates from the Rijnmond Primary Care Database
No full textOBJECTIVE: Osteoarthritis (OA) of the first metatarsophalangeal (MTP) joint is accompanied by pain and stiffness and associated with reduced health-related quality of life. Although prevalence of radiographic 1st MTP joint OA is high, the incidence of clinical 1st MTP joint OA is unknown. Therefore, we aimed to determine the incidence and management of general practice (GP) consultations for symptomatic 1st MTP joint OA. METHODS: A retrospective cohort study was conducted using electronic health records of GPs. An algorithm was defined to identify 1st MTP joint OA patients based on free text and codified data between 2013 and 2022. First MTP joint OA incidence rate, comorbidities and management strategies were assessed. RESULTS: The overall 1st MTP joint OA incidence was 0.74/1000 person-years in patients ≥35 years. The most initiated management by GPs was explanation/reassurance (360/672 (53.6 %)), followed by referral to podiatry (171/672 (25.4 %)) and orthopedic surgeon consultation (162/672 (24.1 %)). Of the 823 patients consulting their GP with foot/toe problems in the year before diagnosis, 491 (47.1 %) were referred to radiology, and 271 (26 %) for orthopedic surgeon consultation. CONCLUSION: The incidence of 1st MTP joint OA has been estimated for the first time in general practice. Most patients are diagnosed after referral to radiology or orthopedic surgeon consultation. From diagnosis, half of 1st MTP joint OA patients are referred, mostly for orthopedic surgeon consultation and podiatry. As evidence for these diagnostic and management strategies is lacking, research into their effectiveness for 1st MTP joint OA in general practice is needed.</p
Ultrashort echo time MRI radiomics as a predictor of clinical outcomes in patellar tendinopathy:Insights from a large prospective clinical trial
No full textPurpose:To evaluate the predictive utility of radiomic features extracted from ultrashort echo time (UTE) MRI in comparison to conventional proton density (PD) sequences for short-term (24-week) and long-term (5-year) clinical outcomes in patients with patellar tendinopathy (PT) receiving exercise therapy. Materials and methods:This prospective study of 76 PT patients undergoing 24-week exercise therapy underwent baseline 3D UTE and PD MRI at 3.0 T. The patellar tendon segmentation used nnU-Net, evaluated with Dice coefficient. Six predictive models consisting of clinical covariates and radiomic features from UTE and PD were developed using Elastic Net with 10-fold cross-validation. Model performance in predicting responsiveness of the patient-reported Victorian Institute of Sports Assessment (VISA-P) score was evaluated using the area under the receiver operating characteristic curve (ROC AUC) and the precision-recall curve (PR AUC), with 95% confidence intervals.Results:The mean Dice similarity coefficient for the automatic segmentation of the patellar tendon from 3D-PD was 0.92 (SD: 0.02) and from 3D-UTE-Cones 0.89 (SD: 0.03). The UTE-based radiomics model demonstrated the highest predictive performance at 24 weeks (ROC AUC: 0.714 [95% CI: 0.701–0.727]; PR AUC: 0.848 [0.837–0.858]), while the PD-based model showed the lowest (ROC AUC: 0.569 [0.553–0.584]; PR AUC: 0.710 [0.692–0.727]). At the 5-year follow-up, UTE radiomics maintained robust performance (ROC AUC: 0.692 [0.677–0.706]; PR AUC: 0.822 [0.810–0.834]), whereas PD radiomics remained limited (ROC AUC: 0.578 [0.561–0.594]; PR AUC: 0.694 [0.676–0.713]).Conclusions:Radiomics features extracted from UTE MRI demonstrate the highest predictive performance for clinical outcomes.</p
Reworking the Visual Legacies of Colonial Photographic Archives With and Through the Self:A Conversation With Dzifa Peters and Nurul Huda Rashid
No full textEsta entrevista dá seguimento ao simpósio “Visual Legacies: Colonial Photographic Archives and the Self”, realizado na Universidade Erasmus de Roterdão em novembro de 2025. O simpósio explorou o potencial das práticas artísticas para reimaginar a imagética colonial e o seu impacto na formação das identidades, apresentando os trabalhos das artistas‑investigadoras Dzifa Peters e Nurul Huda Rashid. Ambas apresentaram as suas investigações, que se dedicam a uma análise crítica dos legados fotográficos coloniais.Dzifa Peters, artista e investigadora germano‑ganesa, parte da sua experiência bicultural para refletir sobre contextos coloniais e diaspóricos. O seu trabalho recorre à fotografia, à fotomontagem e à instalação para expor tensões entre arquivos privados e públicos, enquadramentos institucionais e narrativas pessoais. Trabalha tanto com arquivos vernaculares como institucionais, reelaborando‑os através de narrativas históricas e de reinterpretações imaginativas.Nurul Huda Rashid centra‑se na circulação algorítmica de imagens de mulheres muçulmanas. Através da anotação e de oficinas com mulheres muçulmanas, investiga métodos para perturbar a classificação e a reprodução de imagética dominante, defendendo, assim, modos alternativos de opacidade e visibilidade.Na entrevista, Peters e Rashid discutem a influência das imagens herdadas na autoperceção e nas formas sociais de ver. Exploram o papel da prática artística na contestação dos legados visuais e apresentam estratégias para mitigar o olhar colonial e reelaborar fotografias existentes, promovendo novos sentidos, cuidado e resistência