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PubMed2026

Lineage dynamics of invasive Escherichia coli isolates in the Netherlands from 1975 to 2021: a retrospective longitudinal genomic analysis.

BACKGROUND: Escherichia coli is a common cause of invasive infections such as bloodstream and cerebrospinal fluid infections in neonates. Strains positive for the K1 capsule are considered the most common cause of such neonatal invasive infections. This assumption of K1 dominance, and indeed the population genomics of E coli causing invasive infections in general is largely unstudied. We aimed to provide a comprehensive characterisation of this pathogen population using a longitudinal isolate collection. METHODS: In this analysis we report the findings of the SENTINEL study, a longitudinal genomic analysis of 1790 invasive E coli isolates collected mainly from newborns in the Netherlands between 1975 and 2021 by the Netherlands Reference Laboratory for Bacterial Meningitis, Amsterdam University Medical Centre, Amsterdam, Netherlands. The dataset included all bacterial strains cultured from cerebrospinal fluid or blood in cases of (clinical) bacterial meningitis (1976 to 1980). In 1981 the criteria were expanded to include neonates (aged ≤4 weeks) with E coli sepsis, and from July, 2016 all infants younger than 1 year with E coli sepsis were included. All isolates were sequenced using either the HiSeq 2500 or HiSeq 4000 platforms (Illumina, San Diego, CA, USA). We confirmed species and identified sequence types (STs), detected antimicrobial resistance genes, virulence genes, and the presence of K1 capsule, and characterised the dynamics of these factors over time. FINDINGS: Our data show a highly dynamic bacterial population that is entirely unaffected by antimicrobial resistance determinants. Key pathogen population fluctuations include the complete disappearance of the dominant lineage ST567 and the swapping of dominant ST95 clones from a single serotype O18:H7 clone to two distinct serotype O1:H7 clones, with changes in virulence factors including major fimbrial adhesins. These findings, combined with only 58·8% (1053 of 1790) prevalence in K1-expressing isolates in the entire study population, point to host-pathogen interaction and immune selection pressures as key drivers of bacterial population dynamics in this largely antimicrobial-naive population. INTERPRETATION: Our data show the vital need for ongoing genomic surveillance of microbial pathogen populations to guide appropriate intervention strategies. Additionally, genomic insights of a pathogen population from one specific disease syndrome or patient population cannot always be generalised across other cohorts. FUNDING: Wellcome Antimicrobial and Antimicrobial Resistance Doctoral Training Programme and the National Institute for Health and Care Research Birmingham Biomedical Research Centre.

Netherlands↗

PubMed2025

Triazole-resistant Aspergillus fumigatus in the Netherlands between 1994 and 2022: a genomic and phenotypic study.

BACKGROUND: Aspergillus fumigatus is the main cause of invasive aspergillosis and triazole antifungals are the primary treatment option. The effectiveness of triazole therapy is hampered by the emergence of resistance, mainly caused by mutations in the cyp51A gene and a tandem repeat (TR) of 34 bases (TR34/Leu98His) and 46 bases (TR46/Tyr121Phe/Thr289Ala) in the promoter region, which correspond with signature triazole resistance phenotypes. We aimed to investigate the occurrence of triazole phenotype and genotype variation over a 29-year period in the Netherlands. METHODS: In this genomic and phenotypic study, we screened all clinical A fumigatus isolates from Dutch hospitals collected between Jan 6, 1994, and Dec 31, 2022, for resistance to triazole using agar-based methods, and characterised them by sequencing the cyp51A gene and in vitro susceptibility testing using the European Committee on Antimicrobial Susceptibility Testing reference method. Whole-genome sequencing was performed on selected isolates, including those harboring TR34 variants, high-frequency single-nucleotide polymorphisms, and wild-type strains. Clinical information such as age, underlying disease, diagnosis, therapy, and outcomes was collected for patients who had isolates cultured at the Radboud University Medical Centre, Nijmegen, Netherlands, between Jan 1, 2017, and Dec 31, 2022. FINDINGS: 1979 (15·6%) of the screened 12 679 A fumigatus isolates harboured cyp51A triazole resistance mutations, predominately TR34/Leu98His sensu stricto in 1338 (67·6%) resistant isolates and TR46/Tyr121Phe/Thr289Ala sensu stricto in 332 (16·8%) resistant isolates. Phenotype and genotype variations were observed in 325 (17·2%) triazole resistant isolates harbouring a TR-resistance mechanism, including 12 cyp51A genotype variants. Whole-genome sequencing showed that isolates with combinations of TR34-based and TR46-based polymorphisms seemed to be derived from separate populations, but there was some overlap. 59 cases of proven or probable invasive aspergillosis were identified, including 13 triazole-resistant cases, of which three were caused by genotype variants. Mixed genotype infection was observed in 11 (84·6%) of 13 triazole-resistant patients and the number of antifungal treatment switches was higher compared with triazole-susceptible disease (p<0·0001). INTERPRETATION: Our study showed variation in triazole genotypes and phenotypes in clinical A fumigatus isolates with cyp51A-mediated resistance, some of which were cultured from triazole-resistant invasive aspergillosis cases. Triazole resistance variation and mixed A fumigatus genotypes represent a major challenge in clinical management of Aspergillus diseases because current molecular diagnostic tools will increasingly fail to predict the resistance phenotype, underscoring the need for improved detection methods. FUNDING: National Key Research and Development Program of China, National Natural Science Foundation of China, and Wellcome Trust.

Aspergillus fumigatus↗

PubMed2024

Circulation of avian Chlamydia abortus in the Netherlands and community-acquired pneumonia: an outbreak investigation and retrospective cohort study.

BACKGROUND: In 2021, a novel group of Chlamydia strains in wild birds was classified as avian Chlamydia abortus, with unknown zoonotic potential. We report relevant features of avian C abortus infections from a Dutch family cluster and unrelated historical cases using clinical, epidemiological, and microbiological data. METHODS: An outbreak of avian C abortus started in the Netherlands in December, 2022. Source investigation was done using questionnaires to interview patients and environmental sampling. The outbreak strain of avian C abortus was cultured from three patients from whom sufficient material was available for culture and underwent whole-genome analysis. The outbreak strains and retrospective cohort study strains previously submitted to the National Human Psittacosis surveillance programme in the Netherlands between 2010 and 2022 were typed by partial ompA sequencing. Strains with the same aberrant ompA genotype were further analysed with XerC gene plasmid analysis and compared with closely related Chlamydia sequences available in GenBank. FINDINGS: An avian C abortus strain caused a cluster of respiratory illness in four family members. Three patients were hospitalised with community-acquired pneumonia, one of whom was admitted to the intensive care unit. The faeces of wild birds were considered a probable source for the index infection. For two family members, human-to-human transmission was a plausible route. Ten historical cases could be identified with avian C abortus with the same ompA genotype. All patients had been admitted to hospital, at least five developed pneumonia, and one died. INTERPRETATION: This cluster supports that avian C abortus strains can cause human infections and underlines that human-to-human transmission should be considered when tracing the source of such infections. FUNDING: National Institute for Public Health and the Environment and Dutch Ministry of Agriculture, Fisheries, Food Security and Nature. TRANSLATION: For the Dutch translation of the abstract see Supplementary Materials section.

Humans↗

PubMed2026

Emergence and spread of NA-I223V and NA-S247N double-mutant A(H1N1)pdm09 influenza viruses with reduced oseltamivir susceptibility in the Netherlands and beyond, 2023 to 2026.

In 2023/24, A(H1N1)pdm09 influenza viruses with neuraminidase (NA)-S247N emerged in NA-clade C.5.3.3 carrying NA-I223V, spread internationally, then faded. Such double mutants reappeared sporadically in 2024/25. They expanded again in 2025/26 in NA-clade D.3 viruses carrying NA-S247N after acquiring NA-I223V in Europe - notably Spain, the Netherlands, Finland and France, and beyond. Dutch double mutants from both seasons showed median 12- and 13-fold reduced inhibition by oseltamivir. These findings underscore the need for ongoing genomic and phenotypic monitoring of antiviral susceptibility.

Oseltamivir↗

PubMed2026

Intentions to use different modalities of long-acting HIV PrEP among men who have sex with men and transgender and gender diverse persons in the Netherlands.

Insight into intentions to use long-acting HIV pre-exposure prophylaxis (PrEP) is essential for successful implementation. We assessed intention to use three hypothetical long-acting PrEP modalities (oral, intramuscular and subdermal) among HIV-negative men who have sex with men (MSM) and transgender and gender diverse persons in Amsterdam, recruited through the Amsterdam Cohort Studies (ACS-participants) and social media (survey-participants). Intention was measured per modality using a 7-point Likert scale. We modeled the probability of high intention to use long-acting PrEP using relative risk regression. Of 1258 participants [1231 (97.9%) MSM; 557 ACS and 701 survey; median age 40 years (IQR 32-50)], 76% had ever used oral short-acting PrEP. Intention to use was highest for monthly oral long-acting PrEP [ACS: median 4.5 (IQR 2-6), 38% high intention; survey: median 7 (IQR 6-7), 81% high intention], followed by 2-monthly intramuscular PrEP [ACS: median 3 (IQR 2-5), 19% high intention; survey: median 5 (IQR 3-7), 47% high intention], and implants [ACS: median 2 (IQR 1-4), 9% high intention; survey: median 4 (IQR 2-7), 37% high intention]. PrEP-experienced participants had higher intention to use oral long-acting PrEP and injectables than PrEP-naïve participants. Offering multiple PrEP modalities may improve the acceptability of HIV prevention strategies and increase PrEP uptake and retention in PrEP care.

Humans↗

PubMed2026

289th ENMC international workshop: assessing and managing emerging AAV related toxicities after gene therapy for neuromuscular disorders, 26 - 28 September 2025, Hoofddorp, The Netherlands.

Adeno-associated virus (AAV) mediated gene therapies has emerged as a potentially transformative treatment approaches for neuromuscular disorders, with two FDA-approved products now in widespread clinical use: onasemnogene abeparvovec (Zolgensma) for spinal muscular atrophy and delandistrogene moxeparvovec-rokl (Elevidys) for Duchenne Muscular Dystrophy. However, severe and occasionally fatal adverse events affecting vital organs, including the blood, liver, muscle, and heart, have emerged in both clinical trials and real-world post marketing settings. The 289th European NeuroMuscular Centre (ENMC) workshop convened 38 participants from patient advocacy groups, industry, and preclinical and clinical research groups to collaboratively review these toxicities, their underlying mechanisms, and potential mitigation and monitoring strategies. Discussions addressed the clinical spectrum and biological drivers of these events, the respective roles of innate and adaptive immunity, the contribution of specific vector characteristics as well as of the specific disease and recipient. The application of risk stratification and immunosuppressive regimens for prevention, monitoring, and management were considered. Emerging toxicities, including capillary leak syndrome, endothelial and dorsal root ganglia injuries, were reviewed alongside corresponding preclinical data from non-human primates. Participants agreed on the need to harmonize standard operating procedures, clinical guidelines, and data-sharing practices, and endorsed collaborative initiatives to proactively address critical gaps and unresolved key questions through a patient-centered framework.

Adaptive immune response↗

PubMed2026

Predictive value of Rectal and Throat-nose Screening for the presence of Multidrug-Resistant Organisms in Duodenal Fluid as a Risk of Duodenoscope Contamination: A Multicenter Study.

BACKGROUND: Duodenoscopes have been implicated in patient-to-patient transmission of multidrug-resistant organisms (MDROs). Current gastrointestinal MDRO surveillance relies on rectal screening, yet the duodenum is the primary site of duodenoscope exposure. This study evaluated the predictive value of rectal and throat-nose screening for detecting duodenal MDROs as a marker of duodenoscope contamination risk. METHODS: Adult patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) at tertiary care centers in the Netherlands and India were included. Rectal swabs, throat-nose swabs, and duodenal aspirates were analyzed for MDROs. The detected MDROs were compared using species identification, antibiotic susceptibility patterns, and whole-genome sequencing. RESULTS: Among 512 participants (Netherlands: 339; India: 173), rates of duodenal and rectal MDRO carriage were higher in India (56.6% (98/173); 79.8% (138/173), respectively) than in the Netherlands (5.6% (19/339); 10.3% (35/339)). Given the low prevalence of throat-nose carriage, only the predictive value of rectal screening was assessed. Rectal screening sensitivity for genetically related strains in duodenal fluid was 32.7% in India and 68.4% in the Netherlands . For detecting any duodenal MDRO, sensitivity reached 91.8% in India and 84.2% in the Netherlands, with specificities of 36.0% and 94.1%. Positive predictive value (PPV) was low (India: 65.2%; Netherlands: 45.7%), while negative predictive value was 77.1% and 99%, respectively. CONCLUSIONS: Rectal screening is unreliable for detecting strain-specific duodenal MDROs and overestimates true carriage due to low PPV values. However, it provides excellent rule-out value in low-prevalence settings. Consequently, its utility for guiding infection prevention strategies for duodenoscope contamination is greatest in low-MDRO-prevalence regions.

Bacterial↗

PubMed2026

Treatment of localized rectal cancer in the Nordic countries-comparison of Nordic to Dutch, ESMO, and NCCN guidelines.

BACKGROUND: Rectal cancer treatment in Nordic countries has traditionally differed, especially regarding neoadjuvant treatment. The aim of this review is to give an overview of the current rectal cancer guidelines in the Nordics and compare these to international guidelines. METHODS: Oncologists and colorectal surgeons from the Nordic countries (Denmark, Finland, Norway, and Sweden) and the Netherlands were invited to participate in this narrative review. Two consensus meetings were held to agree on the content. All authors provided recommendations from their national guidelines. In addition, recommendations from the European Society of Medical Oncology (ESMO) and from the US National Comprehensive Cancer Network (NCCN) guidelines were extracted. RESULTS: Several differences between the included guidelines were identified. The radiological "sigmoid take-off" definition for the upper margin of the rectum has been adapted in Denmark and the Netherlands, whereas the other guidelines rely on distance from the anal verge on rigid sigmoidoscopy. Indications for direct surgery vary considerably, where the NCCN guidelines recommend more aggressive neoadjuvant treatment, primarily total neoadjuvant therapy (TNT), the Nordic and European guidelines open for direct surgery more often, and reserve especially TNT for high-risk cases. European countries more often recommend short-course radiotherapy, whereas NCCN maintains chemoradiotherapy as the mainstay. Whereas intentional and opportunistic organ preservation is an established part of the Dutch, NCCN, and ESMO guidelines, its use is mostly restricted to clinical trials in the Nordics. The Nordics and the Netherlands are restrictive in terms of adjuvant treatment, which is frequently recommended in ESMO and NCCN. Whereas neoadjuvant immunotherapy is recommended for mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) rectal cancer in NCCN, this use is off-label in Europe and not routinely recommended. CONCLUSION: Although all guidelines rely on the same evidence, there are considerable differences, especially in the indications and type of oncologic treatment, both in the neoadjuvant and in the adjuvant setting.

Rectal Neoplasms↗

PubMed2026

Microbiological analysis and whole-genome sequencing of Neisseria gonorrhoeae from the microbiological failures in the international, zoliflodacin, phase 3, clinical trial for treatment of uncomplicated urogenital gonorrhoea: a retrospective, genomic, observational study.

BACKGROUND: Zoliflodacin, a first-in-class oral bacterial, DNA gyrase (GyrB) inhibitor, showed non-inferiority to ceftriaxone combined with azithromycin in a recent large international, phase 3, randomised controlled trial for treatment of uncomplicated urogenital gonorrhoea. The aim of this study was to describe the microbiological and whole-genome sequencing (WGS) analyses of paired baseline (pre-treatment) and test-of-cure (TOC) gonococcal isolates from the zoliflodacin phase 3, randomised controlled trial to further characterise and evaluate the protocol-specified microbiological failures with zoliflodacin (n=22) or ceftriaxone and azithromycin (n=1). METHODS: In this retrospective, genomic, observational study, results from antimicrobial susceptibility testing (agar dilution method) of isolates (n=960; 936 baseline isolates from 763 participants and 24 TOC isolates [23 with a paired baseline isolate in the same anatomical site] from 20 participants) collected during the zoliflodacin phase 3, randomised controlled trial done in 16 outpatient clinics in Belgium, the Netherlands, South Africa, Thailand, and the USA (Nov 6, 2019-March 16, 2023) are described. WGS analysis was performed on paired baseline and TOC isolates from participants with microbiological failures (zoliflodacin 44 isolates [19 participants]; ceftriaxone and azithromycin two isolates [one participant]), and the three baseline isolates with highest zoliflodacin minimum inhibitory concentration (MIC 0·5 mg/L). FINDINGS: All isolates were inhibited by the same zoliflodacin concentrations (MICs ≤0·008 to 0·5 mg/L) as wild-type strains cultured internationally in 2013-23. In participants with a microbiological failure after zoliflodacin treatment (n=22, 19 participants), zoliflodacin MIC values for baseline and TOC isolates were similar, and resistance selection was lacking. WGS showed that five (23%) of 22 infections (95% CI 10-43 [in four participants]) of zoliflodacin microbiological failures had different strains at TOC versus baseline. In 17 zoliflodacin microbiological failures (15 participants), isolates at baseline and TOC were indistinguishable. 13 of these 17 microbiological failures, corresponding to 59% (95% CI 39-77; 13 of 22) of all zoliflodacin microbiological failures, were in urogenital or rectal sites in 11 participants and the isolates had zoliflodacin MICs less than or equal to 0·008 to 0·25 mg/L. The single microbiological failure after ceftriaxone and azithromycin treatment had different strains at TOC versus at baseline. No sequenced isolates had mutations associated with elevated zoliflodacin MICs. INTERPRETATION: In the zoliflodacin phase 3, randomised controlled trial, 23% of the zoliflodacin microbiological failures and the single ceftriaxone and azithromycin microbiological failure had different gonococcal strains at TOC versus baseline, which suggests reinfections and not treatment failures. In addition, 59% of the zoliflodacin microbiological failures, all in anogenital sites, had no obvious microbiological explanation based on the low zoliflodacin MICs, previous pharmacodynamic studies, and no evidence of resistance selection after zoliflodacin therapy. A reinfection as the cause for these microbiological failures could not be excluded. We recommend that WGS is implemented in future randomised controlled trials for gonorrhoea treatment to further evaluate possible microbiological failures, exclude reinfections (to avoid underestimating the cure rates), and characterise antimicrobial resistance determinants. FUNDING: GARDP through grants from Germany BMFTR (03KA1831), UK DHSC as part of GAMRIF, Japan MHLW, the Netherlands' Ministry of Health, Welfare and Sport and Directorate-General for International Cooperation, the Federal Office of Public Health of Switzerland, the Canton of Geneva, Switzerland, and Örebro University Hospital, Sweden.

Humans↗

PubMed2026

Effect of Time to Start of Biologic Therapy on Treatment Response in Childhood Arthritis: Results From the UCAN CAN-DU Cohort.

OBJECTIVE: To estimate the effect of time from symptom onset to start of biologic treatment on achieving inactive arthritis within six months in a cohort of patients with juvenile idiopathic arthritis (JIA). METHODS: The international UCAN CAN-DU study prospectively enrolled patients with JIA across Canada and the Netherlands. A nested cohort study was performed and biologic-naive patients with nonsystemic JIA were included at the start of biologic therapy. The primary outcome was inactive arthritis at six months. Demographics, disease-related parameters, and treatment response were compared using (non)parametric tests among early (time symptom onset to biologic start: 0-6 months), intermediate (7-12 months), and late (13-24 months) treatment groups. A logistic regression model analyzed the effect of time to biologic start on the response at six months, adjusting for active joint count and physician global assessment. A graphical representation of the model was created. RESULTS: One hundred and thirty children with JIA were included (early: n = 35; intermediate: n = 46; late: n = 49), 66% were female, and the median age at symptom onset was 11.0 years. The proportion of patients that reach inactive arthritis in the early starters (83%) was significantly higher than in late starters (57%). For each month of delay to the start of biologic treatment, the adjusted odds of having active arthritis after six months of therapy was 1.09 (interquartile range: 1.02-1.17, P = 0.009). CONCLUSION: Early start of biologic therapies in patients with JIA was associated with a higher proportion of patients reaching inactive arthritis within six months, suggesting a window of opportunity to control disease activity.

Humans↗

PubMed2026

Quality over quantity: biopsy-anchored CT radiogenomics models outperform all-lesion training in a multi-tumour cohort despite a smaller sample size.

OBJECTIVE: Radiogenomics aims to non-invasively predict tumour genotypes from imaging, but most studies assume molecular homogeneity by assigning a single biopsy-derived label to all lesions within a patient. This approach risks substantial label noise given well-documented interlesional heterogeneity. We investigated whether anchoring training to biopsy-confirmed lesions improves radiogenomic model performance and generalisability. MATERIALS AND METHODS: We retrospectively analysed 1646 patients (11473 segmented lesions) with contrast-enhanced CT and EGFR mutation status from next-generation sequencing at the Netherlands Cancer Institute, alongside an external NSCLC radiogenomics cohort (n = 158). All visible lesions were segmented, and the exact biopsy site was matched to its segmentation. Radiomic features were extracted, and machine learning models were trained with three lesion selection strategies: all lesions, non-biopsied lesions only, and biopsy-confirmed lesions only. To disentangle label quality from sample size, we created size-matched variants (one lesion per patient) for all-lesion and non-biopsied strategies. RESULTS: All models achieved significant discrimination of EGFR status on internal validation (AUC = 0.62-0.68). However, performance of the all-lesion and non-biopsied models declined on external validation (AUC = 0.55-0.63), while the biopsy-anchored model maintained stable performance (AUC = 0.62), despite having only 1/10th of the training sample size. When training sets were size-matched, the biopsy-anchored approach significantly outperformed a model trained on all available lesions on external validation (p = 0.037). CONCLUSIONS: Radiogenomic models trained on biopsy-confirmed lesions outperform conventional all-lesion strategies in external validation, despite using an order of magnitude fewer samples. Prioritising lesion-level label fidelity can mitigate heterogeneity-driven noise, enhancing robustness and clinical translation of imaging-based genomic prediction. KEY POINTS: Question Does assigning biopsy-derived molecular labels to all lesions introduce heterogeneity-driven label noise that reduces the generalisability of radiogenomic models? Findings Models trained exclusively on biopsy-confirmed lesions demonstrated superior external generalisability compared with all-lesion approaches, despite being trained on substantially fewer samples. Clinical relevance Biopsy-anchored radiogenomics improves the reliability of non-invasive mutation prediction by accounting for tumour heterogeneity, potentially supporting clinical decision-making when tissue sampling is limited or molecular results are discordant across lesions.

Humans↗

PubMed2026

Genetics of major depressive disorder in a homogeneous population with uniform phenotyping.

Harmonized phenotyping and diverse population-specific studies are crucial for advancing gene discovery in psychiatric genetics. We conducted a genome-wide association (GWAS) mega-analysis of DSM-defined lifetime major depressive disorder (MDD) in 64 941 participants (25.7% cases) from the Dutch BIObanks Netherlands Internet Collaboration (BIONIC) consortium. Liability-scale SNP-based heritability was 12.0% (SE = 1.4%) as estimated by LDSC (assuming a lifetime prevalence of 15%) and 26.6% (SE = 1.1%) when estimated by LDAK-REML on individual-level genotype data, indicating substantial common-variant signal in this clinically harmonized sample. The genetic correlation with the latest major depression GWAS from the Psychiatric Genomics Consortium (PGC-MD) was high (rG = 0.89, SE = 0.048). Polygenic scores (PGSs) based on BIONIC predicted depression in UK Biobank, and PGSs derived from PGC-MD predicted MDD in BIONIC, supporting transferability of depression polygenic signal across cohorts and phenotype definitions. Within-family PGS analyses in twins suggested that the observed prediction was not primarily driven by detectable family-level confounding, and twin concordance for MDD increased with polygenic burden. We identified one genome-wide significant locus, indexed by rs3818852 in PALMD, but this finding currently lacks independent replication and should be interpreted cautiously. Finally, genetic correlation and latent causal variable analyses identified multiple traits showing shared or directionally consistent genetic associations with MDD. Together, these findings underscore the value of clinically harmonized phenotyping in regional biobank collaborations for studying the genetic architecture of MDD.

Humans↗

PubMed2026

Online-delivered eye movement desensitization and reprocessing treatment for adults with post-traumatic stress disorder due to multiple traumas: a non-concurrent multiple baseline design.

Background: No controlled studies incorporating randomization have been conducted to investigate the effectiveness of online eye movement desensitization and reprocessing (EMDR) treatment, despite its use in clinical practice.Objective: This study evaluated the effect of online EMDR treatment in adults aged 18-65 years with post-traumatic stress disorder (PTSD) resulting from multiple traumas.Method: A multiple baseline single-case experimental design (n = 21) was employed. Participants were patients with PTSD due to multiple traumas, recruited from a mental healthcare institution in the Netherlands. They were randomly assigned to baseline phases of 2, 3.5, or 5.5 weeks. After this, participants received 10 weekly online EMDR sessions. The primary outcome was the total score on an adapted version of the PTSD Checklist for DSM-5 (PCL-5), which was administered twice a week during baseline and intervention phases, and once 12 weeks after the end of the intervention phase. We performed visual analysis and calculated the improvement rate difference (IRD) for each individual separately to determine whether online EMDR was effective. We also performed a paired t-test and calculated Cohen's d for pretreatment and post-treatment comparisons, and pretreatment versus follow-up to evaluate effects at the group level.Results: Visual analysis and IRD scores showed that the treatment was effective for 15 participants, with effect sizes ranging from small to very large. The mean scores on the PCL-5 at group level decreased significantly over time between pretreatment and post-treatment (Mdiff = 23.6, Cohen's d = 1.34, 95% CI 0.74-1.93), as well as between pretreatment and follow-up (Mdiff = 27.2, Cohen's d = 1.62, 95% CI 0.95-2.27).Conclusion: Most participants showed a reduction in symptoms following the start of the online EMDR. Furthermore, at the group level there was a significant and clinically relevant reduction in symptoms over time. This provides preliminary evidence for the effectiveness of online EMDR treatment.

Humans↗

PubMed2025

Incorporating Epidemiological Data into the Genomic Analysis of Partially Sampled Infectious Disease Outbreaks.

Pathogen genomic data are increasingly being used to investigate transmission dynamics in infectious disease outbreaks. Combining genomic data with epidemiological data should substantially increase our understanding of outbreaks, but this is highly challenging when the outbreak under study is only partially sampled, so that both genomic and epidemiological data are missing for intermediate links in the transmission chains. Here, we present a new dynamic programming algorithm to perform this task efficiently. We implement this methodology into the well-established TransPhylo framework to reconstruct partially sampled outbreaks using a combination of genomic and epidemiological data. We use simulated datasets to show that including epidemiological data can improve the accuracy of the inferred transmission links compared with inference based on genomic data only. This also allows us to estimate parameters specific to the epidemiological data (such as transmission rates between particular groups), which would otherwise not be possible. We then apply these methods to two real-world examples. First, we use genomic data from an outbreak of tuberculosis in Argentina, for which data was also available on the HIV status of sampled individuals, in order to investigate the role of HIV coinfection in the spread of this tuberculosis outbreak. Second, we use genomic and geographical data from the 2003 epidemic of avian influenza H7N7 in the Netherlands to reconstruct its spatial epidemiology. In both cases, we show that incorporating epidemiological data into the genomic analysis allows us to investigate the role of epidemiological properties in the spread of infectious diseases.

Humans↗

PubMed2026

Performance of the IR Biotyper, Nanopore, and Illumina sequencing to discriminate Escherichia coli strains originating from poultry.

UNLABELLED: Escherichia coli is a highly diverse bacterial species that includes avian pathogenic E. coli (APEC), one of the most prevalent causative agents of disease in poultry worldwide. Rapid and accurate discrimination of E. coli strains is essential for outbreak management, antimicrobial resistance surveillance, and vaccine development. In this study, we compared the performance of Fourier Transform Infrared (FTIR) spectroscopy using the IR Biotyper system with Nanopore and Illumina whole-genome sequencing (WGS) for typing 200 E. coli isolates, originating from four poultry rearing farms in the Netherlands. From each farm, we sampled 10 one-day-old meat type rearing chicks, and from every chick, we isolated 5 E. coli strains. FTIR clustering showed strong concordance with WGS-based classifications, particularly serotyping and core-genome similarity determined by PopPUNK analysis (Adjusted Rand Index 0.75-0.92). While Nanopore and Illumina sequencing provided the highest genetic resolution, FTIR offered a faster (max 6 vs 12-28 days for 200 isolates) and more cost-effective alternative for assessing clonality. Across all methods, multiple strains were detected per farm, whereas most birds carried a single dominant E. coli strain. Our findings demonstrate that FTIR provides a reliable and scalable phenotypic method for rapid strain discrimination in E. coli, complementing WGS in diagnostic, surveillance, and epidemiological settings where speed and throughput are critical. IMPORTANCE: Escherichia coli is a major pathogen in poultry and a potential zoonotic risk for humans. Rapid and accurate discrimination of avian pathogenic E. coli (APEC) strains is critical for outbreak management, antimicrobial resistance surveillance, and the design of effective autogenous vaccines. In this study, we compared Fourier Transform Infrared (FTIR) spectroscopy with Nanopore and Illumina whole-genome sequencing for strain typing of E. coli isolates originating from poultry. The results show that FTIR provides comparable clustering accuracy to genomic approaches at a fraction of the time and costs. This work demonstrates that FTIR can serve as a practical, high-throughput alternative for routine monitoring of E. coli in veterinary diagnostics and food safety of poultry meat, enabling faster decision-making and more targeted interventions across the poultry production chain.

Animals↗

PubMed2026

Quantitative trait loci mapping of gene expression and chromatin accessibility in primary fibroblasts reveals shared allelic effects between Latin American and European ancestries.

BACKGROUND: Quantitative Trait Locus (QTL) analysis of molecular data has identified genetic variants associated with traits such as gene expression, and colocalization of these functional QTL with GWAS risk loci has offered insights into the genetic basis of human disease. We employed gene expression (RNA-seq) and chromatin accessibility (ATAC-seq) obtained from human primary fibroblasts to investigate quantitative trait loci (QTLs) in cohorts ascertained for bipolar disorder of European (n = 150) and Latin American (n = 96) ancestries. RESULTS: Leveraging data from three countries of origin (The Netherlands, Colombia, Costa Rica) within our cohort, we characterized differences among individuals at the SNP, gene, and accessible-chromatin levels to compute ancestry-specific expression (e)QTLs and chromatin-accessibility (ca)QTLs. Across ancestries, we observed R2 ≥ 0.93 for eQTL effect sizes and R2 ≥ 0.95 for caQTLs, indicating a high degree of concordance. Integrating chromatin data with expression and genotype information enabled precise fine-mapping of eQTLs, yielding 203 genes with high-confidence (posterior probability > 90%) candidate regulatory pathways. In downstream analyses, transcriptome-wide (TWAS) and chromatin-wide (CWAS) association studies with brain- and skin-related GWAS identified 36 TWAS-significant genes and 77 CWAS-significant open chromatin regions. CONCLUSIONS: These findings underscore the shared genetic regulatory mechanisms across European and Latin American ancestries, while demonstrating that ancestry-specific reference panels enhance the accuracy of TWAS and CWAS in diverse populations. More broadly, this study highlights the value of paired multi-omic datasets from diverse cohorts for interpreting disease-associated genetic variation.

Humans↗

PubMed2026

Transcranial Magnetic Stimulation for Patients with Exposure Therapy Resistant Obsessive-Compulsive Disorder (TETRO): Study Protocol for a Multicenter Randomized Controlled Trial.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a disabling mental disorder, characterized by obsessions, compulsions, and substantial morbidity. Approximately 50% of adults with OCD fail to achieve satisfactory outcomes from first-line treatments, such as exposure therapy with response prevention (ERP), with or without medication. This leads to chronic social, educational, and occupational impairment. While invasive procedures such as deep brain stimulation are available for severe, treatment-refractory cases, a need remains for less invasive alternatives. Repetitive transcranial magnetic stimulation (rTMS), a noninvasive intervention, shows promise in reducing OCD symptoms. Unlike in depression, rTMS is not yet reimbursed for OCD in the Dutch healthcare system. OBJECTIVE: This study examines the efficacy and cost-effectiveness of low-frequency (1Hz) rTMS targeting the presupplementary motor area (pre-SMA) compared to sham rTMS as an adjuvant treatment to ERP in adults with OCD with inadequate response to first-line treatment. METHODS: A total of 250 adults with OCD will be enrolled in this multicenter randomized controlled trial. Participants will be randomly assigned to ERP combined with either active or sham 1Hz rTMS over the pre-SMA. Treatment is administered 4 times weekly for at least 5 weeks (20 rTMS-ERP sessions), with optional extension of 1 to 2 weeks, up to 28 rTMS-ERP sessions. Clinical assessments occur at baseline, weekly during treatment, posttreatment, and at 3, 6, and 12 months follow-up. Participants undergo pre- and posttreatment (functional) (MRI) scans, including a symptom provocation task. Blood sampling takes place pre- and posttreatment and at 3-month follow-up. The primary outcome is OCD severity at posttreatment, as measured by the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Secondary outcomes include functional improvement, quality of life, and societal costs. Pretreatment symptom profiles, genotype, and brain network topology will be analyzed as predictors of response and relapse risk. Pre-to-post treatment change in blood-based and magnetic resonance (MR)-based neuroplasticity markers will help explore differential mechanisms between ERP alone and combined rTMS-ERP. We expect that the verum rTMS protocol will be cost-effective compared to sham-rTMS. RESULTS: Recruitment started in April 2022, and as of February 2026, 201 participants have been enrolled. Posttreatment assessments are projected to be completed in December 2026, with final one-year follow-up evaluations anticipated by the end of 2027. CONCLUSIONS: To our knowledge, this study is the first adequately powered randomized controlled trial examining efficacy, cost-effectiveness, and mechanism of action of rTMS for OCD as adjuvant therapy to ERP. In case of efficacy and/or cost-effectiveness, it will pave the way for rTMS as insured health care for adults with OCD in the Netherlands, and possibly other European countries. Furthermore, this trial will provide insight into the mechanisms of treatment response to intensive ERP, with and without adjunctive rTMS, as well as potential side effects, individual variability, and long-term outcomes in adults with OCD.

Humans↗

PubMed2026

EGFLAM Pathogenic Variants and Congenital Stationary Night Blindness.

IMPORTANCE: Congenital stationary night blindness (CSNB) is a clinically and genetically heterogeneous inherited retinal disorder (IRD), and in many complete CSNB (cCSNB) cases, the underlying genetic cause remains unknown. Uncovering the genetic defects of IRDs helps to refine diagnostic methods and supports the development of specific therapeutic approaches. OBJECTIVE: To describe the phenotype and the underlying gene defect in patients with cCSNB from 2 unrelated families. DESIGN, SETTING AND PARTICIPANTS: This retrospective case series was conducted from January 2023 to July 2025. Data for 3 patients from cohorts of genetically unsolved IRD cases in France (n = 140 for CSNB) and the Netherlands (n = 2730 for IRD) were analyzed clinically and genetically. EXPOSURES: Complete ocular examination, including multimodal retinal imaging and full-field electroretinography (ffERG) incorporating the International Society for Clinical Electrophysiology of Vision standards and multimodal retinal imaging, were performed. Gene defects were identified by genome sequencing (GS) and exome sequencing (ES). MAIN OUTCOMES AND MEASURES: The main outcome was a gene defect, EGFLAM, underlying cCSNB. Measures included phenotyping, GS, ES, Sanger sequencing, and cosegregation analysis. RESULTS: The series included 3 patients from 2 unrelated families of Moroccan ancestry showing high myopia, reduced visual acuity, and night blindness. Retinal imaging depicted myopic changes. ffERG revealed electronegative Schubert-Bornschein configuration in keeping with cCSNB with ON-bipolar cell dysfunction. Patients were lacking pathogenic variants in known genes implicated in IRDs, including CSNB. Two different homozygous pathogenic variants, c.1563_1566del, p.(Val522Glufs*18) and c.1795C>T, p.(Arg599*) in EGFLAM were identified by ES and GS. The corresponding protein is localized in the outer plexiform layer and important for ON-bipolar cell signaling in the retina. CONCLUSION AND RELEVANCE: This case series reports on a gene defect in EGFLAM implicated in human cCSNB. Clinicians should be aware about this association and consider including EGFLAM in diagnostic gene panels for IRDs. This discovery may lead to faster and more accurate diagnosis of cCSNB and genetic counseling, as well as a pathway for developing therapies.

Adolescent↗