Recent publications - Department of Pharmaceutical Biosciences

• Ludvigsen, Lene Ugilt Pagter; Thomsen, Marianne Kragh; Kro, Grete Anette Birkeland; Pedersen, Rune Micha; Gramkow, Ann Maria & Åsberg, Anders [Show all 16 contributors for this article] (2026). Epstein-Barr virus infection monitoring in kidney transplant recipients (EVITA study)—investigating the clinical significance of EBV-DNAemia and the risk of early-onset PTLD. American Journal of Transplantation. ISSN 1600-6135. p. 1–15. doi: 10.1016/j.ajt.2026.07.012. Full text in Research Archive
• Cordero, Christian P.; Brenne, Hanne Britt; Ytteborg, Elisabeth; Hansen, Miroslava; Johansen, Lill-Heidi & Vanrompay, Daisy [Show all 8 contributors for this article] (2026). Immune responses in the olfactory organ and brain of Atlantic cod (Gadus morhua) following nasal vaccination against Francisella noatunensis. Fish and Shellfish Immunology. ISSN 1050-4648. p. 1–40. doi: 10.1016/j.fsi.2026.111767. Full text in Research Archive Show summary

  Bacterial infections caused by the intracellular bacterium Francisella noatunensis pose a major health challenge in Atlantic cod (Gadus morhua), largely due to the lack of effective prophylactic and therapeutic measures. Here we evaluated the immune and physiological responses of cod to two candidate live attenuated vaccines (i.e. clpB and iglC) against F. noatunensis delivered intranasally. These experimental vaccines were constructed by a single knockout mutation of a virulence gene in F. noatunensis. Cod was vaccinated intranasally and reared for 45 days until infection with the wild-type strain Francisella noatunenesis subp. noatunensis and further reared for 47 days until termination. Given the chosen delivery route, our analyses were focused on the olfactory organ and brain of cod. Infected cod presented classic gross pathologies of francisellosis, including multi-organ nodulations, splenomegaly, and hepatomegaly. Among the vaccine candidates, the clpB-vaccinated group demonstrated upregulated expression of immune response genes in both the olfactory organ and brain, exhibited the lowest nodulation score, and showed minimal histological alterations in the olfactory organ. To further explore the physiological consequences of the clpB mutant, shotgun proteomics was performed in selected olfactory organ and brain of vaccinated cod. We identified 404 differentially expressed proteins (DEPs) in the brain and 241 in the olfactory organ with 17 DEPs common to both organs. These DEPs were mostly involved in cellular signalling, transmembrane internalisation, enzymatic processes, and important immune response pathways, such as immune recruitment and activation, the respiratory burst reaction, and apoptosis. These findings suggest that the clpB-attenuated vaccine holds promise as a candidate vaccine against F. noatunensis and provides valuable insights into the mechanisms of immune modulation.

• Avershina, Ekaterina; Birkeland, Einar Elvbakken; Johannessen, Cecilie Bucher - & Rounge, Trine Ballestad (2026). CRISPR-Cas immune repertoires as an ecological record of bacterial interactions with mobile genetic elements in the human gut. Gut microbes. ISSN 1949-0976. 18(1). doi: 10.1080/19490976.2026.2734649. Full text in Research Archive
• Mjønes, Harald Stranger; Havik, Mona; Seferi, Gezime & Morland, Cecilie (2026). High-intensity interval exercise affects neurogenesis and angiogenesis differently in diabetic and non-diabetic mice. Frontiers in Neuroscience. ISSN 1662-4548. 20, p. 1–12. doi: 10.3389/fnins.2026.1927709. Full text in Research Archive
• Corfield, Elizabeth Claire; Shadrin, Alexey; Frei, Oleksandr; Rahman, Mohammad Zillur; Akdeniz, Bayram Cevdet & Filiz, Tahir Tekin [Show all 29 contributors for this article] (2026). Family genetic designs in MoBa provide insights into health and functioning. Nature. ISSN 0028-0836. doi: 10.1038/s41586-026-10926-5. Full text in Research Archive Show summary

  Genome-wide association studies using large, population-based samples of unrelated individuals have discovered thousands of genetic associations with health and disease1. These studies can help explain genetic and environmental risks. However, increasing evidence suggests that population-based estimates, while precise, can also reflect confounding that affects their use and interpretation. This confounding can be overcome using data from genotyped family members, such as nuclear mother–father–child trios2,3. However, samples of genotyped families are rare4,5,6,7,8,9,10,11. Here we illustrate some of the advantages of familial data using the Norwegian Mother, Father and Child Cohort Study (MoBa), a population-based cohort of parents and offspring with extensive genotype data (n ≈ 230,000) (ref. 3), along with broad and longitudinal phenotyping of health and functioning. We provide an overview of MoBa and describe the quality control of genotype data tailored to this extensively related sample. We then use trio data to illustrate how family-based genomic designs can identify distinct direct and indirect sources of genetic influence and structural confounding. As examples, we analyse children’s height, educational achievement, depressive symptoms and sleep duration. These demonstrations highlight MoBa as a broadly valuable resource for advancing understanding of health and functioning across the lifecourse and generations.

• Glenna, Susanne; Birkeland, Einar Elvbakken; Orr, Russell; Gilfillan, Gregor; Dalland, Marianne & Økstad, Ole Andreas Løchen [Show all 8 contributors for this article] (2026). Longitudinal analysis of the hand microbiome in response to chlorine-based antiseptic use during a military field exercise. Microbiology spectrum. 14(8). doi: 10.1128/spectrum.03771-25. Full text in Research Archive
• Averina, Maria; Brun, Atle; Skadberg, Øyvind; Løfblad, Lena; Michaelsen, Anette Kristine & Bergan, Stein [Show all 15 contributors for this article] (2026). Performance of the European Kidney Function Consortium (EKFC) creatinine-based eGFR equation and other eGFR equations in a north European population. A multicentre study in Norway. Clinical Chemistry and Laboratory Medicine. ISSN 1434-6621. doi: 10.1515/cclm-2026-0464. Full text in Research Archive Show summary

  Objectives Accurate estimation of glomerular filtration rate (eGFR) is necessary for early detection and staging of chronic kidney disease (CKD), risk stratification, and guiding therapies that prevent complications and progression to advanced CKD. This study aimed to evaluate the performance of different eGFR equations in a large national cohort. Methods This multicentre study was conducted at six university hospitals in Norway. Retrospective data from patient’s medical records from 2005 to 2024 for 5,552 adults and 2,981 children were used to validate several creatinine-based eGFR equations against measured GFR (mGFR) by Iohexol clearance. Performance was assessed using median bias and P30 accuracy (proportion of eGFR within ±30 % of mGFR). Results The European Kidney Function Consortium (EKFC) creatinine-based eGFR equation outperformed the CKD-EPI 2009 and 2021, the Modification of Diet in Renal Disease (MDRD) in adults, the Schwarts bedside and the CKiD U25 equations in children ≥2 years and was comparable to the Lund-Malmö equation (LM) in adults. Both CKD-EPI equations had the lowest accuracy and were overestimating GFR in young people (<25 years) and elderly patients (≥65 years). Replacing the CKD-EPI equations with the EKFC equation will result in lower eGFR values and a higher prevalence of CKD stages 3–5. Replacing the LM and MDRD with the EKFC equation will result in higher eGFR and a lower prevalence of CKD stages 3–5. Conclusions The EKFC equation was overall the best suited creatinine-based eGFR equation for this Norwegian population from 2 years of age. Clinicians should be informed about clinical implications of shifting from other equations to the EKFC equation.

• Birkeland, Einar Elvbakken; Kværner, Ane Sørlie; Avershina, Ekaterina; Johannessen, Cecilie Bucher -; Bemanian, Vahid & Blix, Hege Salvesen [Show all 14 contributors for this article] (2026). Microbiome signatures for detection of colorectal lesions in population-based FIT screening. Nature Communications. 17. doi: 10.1038/s41467-026-75962-1. Full text in Research Archive Show summary

  The gut microbiome has been linked to colorectal cancer (CRC) development, with microbe-based classifiers distinguishing between CRC patients and healthy controls. However, there is a lack of studies addressing the utility of the microbiome in screening-relevant settings, including both precancers and CRC. In this Norwegian population-based study, we used fecal immunochemical test (FIT) leftovers from 1034 FIT-positive (i.e. positive for occult blood) screening participants for gut metagenome profiling using shotgun sequencing. Using comprehensive clinical, demographic, and lifestyle data, we modeled gut microbiome associations with CRC screening outcomes. Combining microbial profiles with quantitative FIT values improved detection of premalignant lesions beyond optimizing the FIT value alone, even after incorporating established CRC risk factors. Still, the FIT value maintained superior discriminative ability for CRC. We confirmed enrichment of bacteria such as Fusobacterium nucleatum and Peptostreptococcus stomatis in CRC. In contrast, other bacteria previously associated with the presence of CRC, including Hungatella hathewayi and Clostridium symbiosum, as well as pks-negative Escherichia coli, were enriched in those with no neoplastic findings, suggesting that in a FIT-positive population their presence may reflect other conditions causing intestinal bleeding rather than underlying neoplasia. Microbial profiles were predominantly associated with distal rather than proximal lesions. Together, our findings highlight the potential for microbial markers to improve FIT-based CRC screening, especially by differentiating those with premalignant lesions from those who test FIT-positive for other reasons.

• Rødevand, Linn Nilsen; Rahman, Mohammad Zillur; Jaholkowski, Piotr Pawel; Parker, Nadine; Valdimarsdóttir, Unnur Anna & Smeland, Olav Bjerkehagen [Show all 14 contributors for this article] (2026). Evidence for overlapping genetic architecture between lifestyle factors and severe mental disorders with different patterns across diagnoses. EBioMedicine. 128. doi: 10.1016/j.ebiom.2026.106304. Full text in Research Archive
• Krebs, Kristine; Luitva, Laura Birgit; Kõre, Anette Caroline; Kokasaar, Raul; Jõeloo, Maarja & Hudjashov, Georgi [Show all 19 contributors for this article] (2026). Pharmacokinetic recall study of Estonian Biobank participants with novel genetic variants in CYP2C19 and CYP2D6. NPJ GENOMIC MEDICINE. 11(1). doi: 10.1038/s41525-025-00549-6. Full text in Research Archive Show summary

  CYP2C19 and CYP2D6 are involved in the hepatic metabolism of approximately 35–40% of clinically used drugs. We conducted an in vivo phenotyping study encompassing 114 Estonian Biobank participants to evaluate the functional impact of rare or novel single-nucleotide and structural variants in the CYP2C19 and CYP2D6 genes using omeprazole and metoprolol as respective probe drugs. Plasma concentrations of these drugs and their metabolites were measured at 10 time points, and parent drug-to-metabolite ratios were calculated to determine enzymatic activity. Long-read sequencing enabled high-resolution star allele calling. Our results provide the first in vivo confirmation that partial gene and intragenic deletions in CYP2C19 (CYP2C19*37 and CYP2C19*42), enriched in Estonians and Finns, are associated with poor metaboliser phenotypes (P < 1.2 × 10−7). Additionally, we offer in vivo evidence of reduced metabolic activity of the CYP2D6*124 allele and a novel missense variant (c.940C>A) in exon 6 of CYP2D6. Furthermore, we observed that inhibitor exposure was significantly associated with higher metabolic ratios for both CYP2C19 (P = 3.0 × 10−6) and CYP2D6 (P = 0.02). Our findings emphasise the importance of identifying genetic variants in CYP2C19 and CYP2D6 beyond commonly assessed star alleles and that profiling for drug interactions can provide more precise assignments of metabolic phenotypes and improve personalised treatment.

• Bergh, Marianne Skov-Skov; Bogen, Inger Lise; Vevelstad, Merete Synnøve Horn & Øiestad, Åse Marit Leere (2026). Psilocin glucuronide in whole blood: a stable and useful biomarker of psilocybin intake. Journal of Analytical Toxicology. ISSN 0146-4760. 50(4). doi: 10.1093/jat/bkag015. Full text in Research Archive
• Lumor, Josephine Sena; Nyberg, Henriette Eckhardt; Nerem, Elisabeth; Andersen, Jannike Mørch & Bogen, Inger Lise (2026). Long-term effects of adolescent THC exposure on anxiety-like behavior and cognitive function in male rats. Psychopharmacology. ISSN 0033-3158. doi: 10.1007/s00213-026-07067-y. Full text in Research Archive Show summary

  Rationale As cannabis legalization and decriminalization have expanded, it is increasingly perceived as a low-risk substance. Concurrently, the potency of cannabis products and the number of young adults seeking treatment for cannabis use disorder have risen markedly. A growing body of research links early onset, frequent use, and high potency cannabis products to a range of adverse outcomes. Objective This study aimed to examine whether frequent cannabis use during late adolescence affects cognitive functioning and increases the risk of developing anxiety in adulthood. Methods Male Sprague-Dawley rats were administered tetrahydrocannabinol (THC; 5 mg/kg/day) or vehicle from postnatal day (PND) 42 to 62. After a drug-free period, anxiety-like behavior was assessed in the elevated plus maze (EPM) and Light-Dark transition tests, while cognitive function was evaluated in the novel object recognition and Morris water maze (MWM) tests. THC concentrations in blood and brain tissue were quantified using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Results The rats displayed blood THC concentrations comparable to human cannabis users and reduced body weight during the exposure period – an effect that persisted for over two months following the final injection. Adolescent THC exposure impaired novelty preference in young adult animals, whereas effects on spatial memory were less definitive. THC-exposed rats showed anxiety-like behavior in the EPM test, but not in the Light-Dark transition test. Conclusion Our findings suggest that frequent cannabis exposure during adolescence may lead to long-term reductions in body weight, reduced novel object recognition, and increased vulnerability to certain aspects of anxiety-related behavior in adulthood.

• Glatkauskas, Mikas; Syversen, Malin Olsen; Mathiesen, Liv; Scott, Michael; Svensberg, Karin & Denstad, Berit Gallefoss [Show all 7 contributors for this article] (2026). Perspectives on shared decision making related to medications from patients with multiple long-term conditions transitioning from hospital to home: a qualitative study. International Journal of Clinical Pharmacy. ISSN 2210-7703. doi: 10.1007/s11096-026-02143-x. Full text in Research Archive Show summary

  Introduction Shared decision making is particularly important for patients with multiple long-term conditions due to the nature of long-term treatments and frequent changes in medication regimens. However, the complexity of the medication regimens could exclude these vulnerable patients from shared decision making. There is little knowledge about how patients with multiple long-term conditions experience and perceive shared decision making. Aim The aim was to explore the perspectives and experiences of patients with multiple long-term conditions regarding shared decision making related to medications before, during and after a hospital stay. Method Semi-structured interviews with 21 patients and three next of kin were conducted. Patients ≥ 18 years, usually living at home, on at least four medications for at least two separate conditions were included. These patients were purposively sampled from two geriatric wards and one internal medicine ward at a university hospital in Norway and interviewed approximately 14 days post hospital discharge. The inclusion and interviews lasted from December 2022 to February 2024. A semi-structured interview guide was used, and the qualitative data were analyzed using directed content analysis guided by the three-talk model developed by Elwyn et al. from 2017. Results Patients reported not being invited to be part of the shared decision-making process and perceived their limited medical knowledge as a barrier to being invited to participate. They reflected on themselves being primarily focused on single details regarding one medication option they had received. Furthermore, they were not encouraged by the healthcare professionals to discuss and compare different medication options. Both patients and next of kin described an expectation that decisions being made by healthcare professionals would be accepted although the patient did not necessarily understand the treatment plan adequately. Several patients reported that healthcare professional led decisions left little to no room for further discussion and that medication decisions and patient health goals were almost solely in the hands of the healthcare professional. Although most patients trusted the healthcare professional to act in their best interests, this reliance resulted in further disengagement from their own treatment. Conclusion Patients with multiple long-term conditions were in general unfamiliar with and uninvolved in shared decision making related to medications. Additionally, the patients reflected on a lack of invitation to team talk which resulted in limited patient involvement both in option and decision talk.

• Staniszewska, Magdalena; Hübner, Ralph; Locatelli, Camilla; Howard, Douglas; Forni, Matilde & Man, Francis [Show all 13 contributors for this article] (2026). Ensuring enantiomeric consistency in FAPI radiopharmaceuticals: comparative analysis of (S)- and (S/R)-FAPI-46/-74 confirms pharmacological equivalence. EJNMMI Radiopharmacy and Chemistry. 11(1). doi: 10.1186/s41181-026-00432-4. Full text in Research Archive Show summary

  Background Enantiomeric composition may impact binding and potentially performance of a drug product but is not routinely tested and minimum acceptance criteria are not always established. Some batches of the precursors FAPI-46 and FAPI-74 used clinically contain a mixture of (S)- and (R)-enantiomers. This study investigates the in vitro pharmacodynamic characteristics of different enantiomeric compositions of FAP-targeting radioligands FAPI-46 and FAPI-74 and in vivo pharmacokinetics of FAPI-46 in naïve mice. Results (S)-, (R)-, and (S/R)-enantiomers of radiolabeled FAPI-46 and FAPI-74 were evaluated for stability in human serum, binding affinity, internalization, retention, and selectivity using HT1080-hFAP cells and HEK293-hCD26 cells. All enantiomeric compositions showed high stability in human serum with minimal serum protein adhesion. (S)- and (S/R)-enantiomers exhibited comparable binding, internalization, and retention characteristics. High selectivity for FAP over CD26/DPP4 was maintained. (R)-enantiomers showed no specific binding to FAP. Additionally, the same enantiomers of 68Ga-labeled FAPI-46 were evaluated by dynamic positron emission tomography (PET) imaging (0–60 min post-injection) and ex vivo organ biodistribution in naïve BALB/c mice (10, 30, and 60 min, or 4 h post-injection) to compare their pharmacokinetic profiles. PET imaging revealed nearly identical time-activity curves for the enantiomers of [68Ga] Ga-FAPI-46, indicating similar whole-body distribution within 1 h post-injection, with rapid renal clearance and minimal muscle uptake. Ex vivo organ biodistribution confirmed comparable pharmacokinetic profiles between enantiomers, with no significant differences in tissue distribution. Conclusion These findings provide important validation that current clinical (S/R)-mixtures of FAPI-46/-74 exhibit pharmacokinetic and pharmacodynamic behavior comparable to pure (S)-enantiomers, supporting regulatory confidence and cross-trial reproducibility in the global FAPI-46/-74 imaging landscape.

• Boffel, Laura; Baets, Hanna De; Heughebaert, Liesl; Rispens, Theo; Åsberg, Anders & Shipkova, Maria [Show all 11 contributors for this article] (2026). To Convert or Not to Convert? Official International Association of Therapeutic Drug Monitoring and Clinical Toxicology Guideline: Considerations and Recommendations for Converting Capillary Blood Microsampling Concentrations to Plasma Concentrations. Therapeutic Drug Monitoring. ISSN 0163-4356. 48(1), p. 1–26. doi: 10.1097/ftd.0000000000001393. Full text in Research Archive Show summary

  Background: Capillary blood microsampling enables the sampling of small blood volumes, making it suitable for vulnerable populations, remote collection, and repeated sampling. Owing to its minimal invasiveness, blood microsampling has emerged as an alternative to venipuncture in many fields. However, as capillary blood differs from venous blood in composition and analytes vary in their distribution between the blood cell and plasma fractions, plasma and capillary blood concentrations may differ. Because plasma is often the standard matrix for routine analyses, this discrepancy can compromise the clinicians' interpretation of capillary blood results. Hence, to ensure comparability with results obtained through plasma-based assays and reference ranges, accurate conversion to plasma concentrations may be required, which may improve the reliability and validity of microsampling-based outcomes. Despite its relevance, guidance on whether conversion is appropriate or desired and on how to translate and validate the translation of capillary blood microsampling results to plasma concentrations is lacking. Method: To address this gap, members of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT) expert committees have prepared this guideline to discuss the “what, when, and how” of converting capillary to plasma concentrations and provide guidance on the decision of fit-for-purpose conversion. In addition, guidance to assess capillary blood results when the reference matrix is whole blood and to assess liquid capillary plasma results is provided. The included topics, as well as considerations and recommendations presented in this guideline, were based on a previously published dried blood spot-based IATDMCT guideline, literature review and expert opinions of the authors. Results and conclusions: Key points include the importance of conducting a comprehensive clinical validation study to fully understand capillary blood microsampling results. In addition, the performance of the conversion method should be evaluated case by case, as it depends on both the microsampling-based method and analyte of interest. Furthermore, an independent set of paired capillary and venous samples should be used to validate an established conversion formula. Finally, a key point for future studies is to focus on the clinical impact of (converted) capillary blood concentrations in comparison with decisions based on results in the reference matrix to guarantee any microsampling-based outcome.

• Kværner, Ane Sørlie; Birkeland, Einar Elvbakken; Avershina, Ekaterina; Botteri, Edoardo; Bucher-Johannessen, Cecilie & Knudsen, Markus Dines [Show all 14 contributors for this article] (2026). Alcohol consumption and colorectal carcinogenesis: an exploration of the gut microbial pathway as a potential mediator. European Journal of Nutrition. ISSN 1436-6207. 65(4), p. 1–18. doi: 10.1007/s00394-026-03960-6. Full text in Research Archive Show summary

  Background Alcohol consumption is one of the major risk factors of colorectal cancer (CRC), yet the mechanisms underlying this relationship, particularly the role of gut microbes, are not fully understood. Objective To study associations of alcohol intake with the gut microbiome and colorectal lesions among CRC screening participants. Of particular interest was the potential role of gut microbes in mediating the association between alcohol intake and colorectal lesions. Methods Screening participants with a positive faecal immunochemical test at ages 55–77 were eligible for the CRCbiome study. Alcohol intake was assessed using a validated, semi-quantitative food frequency questionnaire and linked with shotgun metagenome based gut microbial profiles to study associations with screen-detected colorectal lesions. The potential role of alcohol-associated gut microbes in mediating the association between alcohol intake and colorectal lesions was examined using causal mediation analysis. Results Of 1468 participants with dietary data, 414 were diagnosed with advanced lesions. Alcohol intake was positively associated with advanced lesions in a dose-dependent manner (ptrend = 0.008), with odds ratio of 1.09 (95% confidence interval, 1.00, 1.19) per 10 g/day increase. Compared to non-consumers, those consuming alcohol were characterized by a distinct microbial profile, manifested as modest, but consistent, shifts in α- and β-diversity, and differentially abundant bacteria. A causal mediation analysis showed that 12% of the association between alcohol intake and advanced lesions was mediated by alcohol-associated gut bacteria. Conclusion Alcohol consumption was associated with a distinct microbial profile, which partly explained the association between alcohol intake and advanced colorectal lesions.

• Knudtzon, Stephanie; Kirsebom, Bjørn-Eivind; Pålhaugen, Lene; Bettella, Francesco; Gisladottir, Berglind & Bahrami, Shahram [Show all 19 contributors for this article] (2026). Genotype–phenotype interaction in Alzheimer's disease immune activation. Alzheimer's & Dementia. ISSN 1552-5260. 22(1). doi: 10.1002/alz.70978. Full text in Research Archive Show summary

  Introduction: Alzheimer's disease (AD) is a neurodegenerative disorder influenced by genetic factors, particularly related to immune activation. This study examines genotype-phenotype interactions affecting immune responses in AD as a reaction to neurodegeneration. Methods: We computed AD polygenic risk scores (PRSs) informed by shared AD-autoimmunity genetics (AD PRSINFL), AD-independent immune activation score from 10 autoimmune diseases (sum PRSIMMUNE), and standard AD PRSs for 294 individuals. Cerebrospinal fluid (CSF) immune markers (sTREM2, clusterin, fractalkine, and chitinase 3 like protein (YKL-40)) were regressed on PRSs, and their interaction with neurodegeneration markers (total tau [t-tau] or neurofilament light chain [NfL]). Results: High AD PRSINFL scores correlated with lower sTREM2 (β = −0.18, p < 0.01), clusterin (β = −0.12, p < 0.05), and fractalkine (β = −0.13, p < 0.05) levels in cases with elevated t-tau. High sum PRSIMMUNE score correlated with lower clusterin in cases with elevated NfL (β = −0.12, p < 0.05). Discussion: Genetic predisposition for immune activation might cause unfavorable immune response in early AD.

• Lair, Benjamin; Cazorla, Clément; Lobeto, Alicia; Labour, Axel; Couloutchy, Lorenzo & Laurens, Claire [Show all 11 contributors for this article] (2026). MyoFuse is a fully AI-based workflow for automated quantification of skeletal muscle cell fusion in vitro. Scientific Reports. 16(1). doi: 10.1038/s41598-026-40047-y. Full text in Research Archive Show summary

  The fusion index (FI) is widely used to assess myoblast differentiation into myotubes, but manual quantification is tedious and biased. Existing automated methods face limitations in nucleus segmentation and classification and often misidentify myoblast nuclei located above or below myotubes, leading to FI overestimation. To address these issues, we developed MyoFuse, an AI-based workflow enabling fully automated and unbiased FI quantification. MyoFuse combines nucleus segmentation using Cellpose with a classification network trained with Svetlana on fluorescence images of mouse C2C12 and human primary myotubes. Performance was evaluated by comparing MyoFuse-derived FI values with expert annotations and by assessing classification accuracy at the single-nucleus level. MyoFuse achieved strong accuracy scores in mouse C2C12 and human primary myotubes (0.954 and 0.911 respectively), and showed strong correlations with expert-derived FI values (r = 0.991 and r = 0.937 respectively; p < 0.0001). Unlike current approaches that overestimate FI, MyoFuse reliably segments nuclei even within dense clusters and distinguishes myotube from myoblast nuclei based solely on cytoplasmic staining. By processing large images, it further reduces selection bias and accounts for heterogeneity in myotube density. MyoFuse thus provides a robust, high-throughput, and accurate method for FI quantification in skeletal muscle cell culture.

• Akdeniz, Bayram Cevdet; Bahrami, Shahram; Hagen, Espen; Fuhrer, Julian; Fominykh, Vera & Shadrin, Alexey [Show all 108 contributors for this article] (2026). Polygenic Hazard Score for Predicting Age-associated Risk of Alzheimer’s Disease in European Populations: Development and Validation. medRxiv. doi: 10.1101/2025.07.28.25332293. Full text in Research Archive Show summary

  Abstract Objectives Polygenic hazard score (PHS) models can be used to predict the age-associated risk for complex diseases, including Alzheimer’s disease (AD). In this study, we present an improved PHS model for AD that incorporates a large number of genetic variants and demonstrates enhanced predictive accuracy for age of onset in European populations compared to alternative models. Methods We used the genotyped European Alzheimer & Dementia Biobank (EADB) sample (n=42,120) to develop and evaluate the performance of the PHS model. We developed a PHS model building on 720 genetic variants, including Apolipoprotein E ( APOE ) ε2 and ε4 alleles. We used Elastic Net-regularized Cox regression approach to develop the PHS model. Results The new PHS model (EADB720) improved prediction accuracy compared to alternative models in European populations, with the Odds Ratio OR80/20 from the highest quintile of risk (80th risk percentile and above) to the lowest quintile of risk (20th risk percentile and below) varying between 5.10 and 13.15 within the range of age of onset from 65 – 85 years. Our model also improved risk stratification across ε3/3 individuals of European ancestry (OR80/20 ranges from 1.95 to 3.52). It was also successfully validated in independent datasets (HUSK, DemGene and ADNI) by achieving OR80/20 up to 10.00 in each independent dataset. Conclusion Our EADB720 model significantly improves the accuracy of age-associated risk of AD across European populations (pval<0.03). Accurately predicting the age of onset of AD is of large clinical importance to implementing new AD medication and early intervention in clinical settings.

• Förster, Pia Marlene; Hogenkamp, Julian; Pottgießer, Moira Fee; Binsch, Christian; Humpert, Awovi Didi & Brügge, Carolin Laura [Show all 14 contributors for this article] (2025). High-resolution analyses of the secretomes from murine C2C12 cells and primary human skeletal muscle cells reveal distinct differences in contraction-regulated myokine secretion. Frontiers in Physiology. 16. doi: 10.3389/fphys.2025.1549316. Full text in Research Archive Show summary

  Myokines released by skeletal muscle in response to contraction may contribute to the health-promoting effects of exercise. Previous studies with cultured rodent and human myotubes have revealed highly complex patterns of myokine secretion. However, the commonalities and differences in the secretory response of the different cell models have not been explored, limiting the interpretation of these results. In the present study, we performed a comprehensive analysis of contraction-regulated secretomes using the most commonly used skeletal muscle cell models, cultured murine C2C12 myotubes and satellite cell-derived primary human myotubes (HSkMC). The cells were subjected to low-frequency electrical pulse stimulation (EPS) for 6 h followed by high-resolution mass spectrometry analysis of secreted proteins in the culture medium. We identified 5,710 and 3,285 proteins in the secretomes of C2C12 myotubes and HSkMC, with 80% of human myokines also detected in the murine secretome. Additionally, we found 518 and 336 secreted proteins that were differentially regulated during contraction in murine and human cells, respectively, along with 1,440 and 385 previously unknown potential myokines secreted by murine and human myotubes. Bioinformatic prediction analyses revealed that the majority of the newly identified myokines were secreted via unconventional protein secretion pathways (UPS) in the murine secretome, whereas most novel proteins in the human secretome were secreted via the classical endoplasmic reticulum (ER)-to-Golgi pathway. Moreover, ontology analysis indicates cell type-specific differences in cellular compartments involved in myokine secretion. Collectively, our results provide a comprehensive overview of the secretomes of two of the most commonly used cell models and may provide guidance for further studies of myokines.

• Slon-Roblero, Maria Fernanda; Stel, Vianda S.; Sanchez-Alvarez, Emilio; Escola, Joaquín Manrique; Dias, Bruno José Fraga & Auñón, Antonio Sarrión [Show all 28 contributors for this article] (2025). Trends in home dialysis over the last decade in Europe: an ERA Registry study. Nephrology, Dialysis and Transplantation. ISSN 0931-0509. 41(3), p. 457–475. doi: 10.1093/ndt/gfaf171. Full text in Research Archive Show summary

  Background Home dialysis therapies could offer benefits to individuals undergoing dialysis. This study examines trends of home dialysis, including home haemodialysis (HHD) and peritoneal dialysis (PD) across European countries from 2012 to 2021, and evaluates transitions between home dialysis and other kidney replacement therapies (KRT). Methods Data from adult patients undergoing KRT in 13 European countries were obtained from the European Renal Association Registry. Trends in home dialysis initiation, the number of patients receiving home dialysis by 31 December of each year, and transitions before and after home dialysis were analysed. Results Between 2012 and 2021, 65 246 adults initiated PD and 7878 HHD. Over the last decade, HHD initiation rates and prevalence increased, while those for PD declined, resulting in a stable overall home dialysis initiation rate and prevalence. Home dialysis accounted for 5.8% of the total KRT prevalence. Most HHD patients transitioned from in-centre HD (ICHD, 76.6%), whereas 86.9% of PD patients had no prior KRT. Two years after initiation, 53.2% of HHD patients remained on HHD, 20.9% received a kidney transplant (KT), 16.6% transitioned to ICHD, 8.1% died while on HHD and 0.6% switched to PD. Among PD patients, 39.6% remained on PD, 22.6% transitioned to ICHD, 18.3% received a KT, 17.4% died while on PD and 0.3% switched to HHD. Conclusions While the use of HHD over the past decade increased in some European countries, the use of PD has declined. The prevalence of both HHD and PD remains low, with limited transitions from other KRT options to home dialysis and between home dialysis modalities. These findings highlight the need for more effective, region-specific strategies to improve access to these modalities for patients who may benefit from it.

• Risnes, Louise Fremgaard; Brottveit, Margit; Robertsen, Ida; Ibsen, Jostein Holen; Aabakken, Lars & Johannesen, Marie Kongshaug [Show all 12 contributors for this article] (2025). Research Communication: Teriflunomide Does Not Affect Gluten-Specific T-Cell Activity in Coeliac Disease—A Randomised, Placebo-Controlled Trial. Alimentary Pharmacology and Therapeutics. ISSN 0269-2813. 62(10), p. 1027–1031. doi: 10.1111/apt.70301. Full text in Research Archive Show summary

  Coeliac disease is an autoimmune disorder driven by gluten and managed through a strict gluten-free diet. We tested teriflunomide, a drug known for its ability to alter T-cell activity, in a phase 2a trial of 15 patients with coeliac disease. Participants received teriflunomide or placebo including a loading dose, followed by a 3-day oral gluten challenge to monitor T-cell responses. The main aim was to observe attenuation of gluten-specific T-cell activation markers after gluten exposure. We found no significant differences in T-cell activity between groups, concluding that teriflunomide is ineffective as a non-dietary treatment for coeliac disease

• Baarset, Anne Marte; Steinsland, Synne; Nerem, Elisabeth; Andersen, Jannike Mørch; Baumann, Michael H. & Bogen, Inger Lise (2025). Pharmacological effects and pharmacokinetics of the novel synthetic cathinone α-pyrrolidinoisohexanophenone (α-PiHP) compared with α-pyrrolidinovalerophenone (α-PVP) in mice. Neurotoxicology. ISSN 0161-813X. 108, p. 412–421. doi: 10.1016/j.neuro.2025.05.005. Full text in Research Archive
• Zhou, Wenjing; Martinez-Garcia, Elena; Sarnow, Katharina; Kanli, Georgia; Nazarov, Petr V & Li, Yaquan [Show all 37 contributors for this article] (2025). Development of a highly differentiated rat brain organoid model for exploring glioblastoma invasion dynamics and therapy. Neuro-Oncology. ISSN 1522-8517. doi: 10.1093/neuonc/noaf271. Full text in Research Archive Show summary

  Background: Human brain organoids (BOs) are important models for studying early brain development and neurological disorders. While techniques for creating BOs are advancing, they remain developmental structures. Therefore, when human BOs are used to studying glioma–host interactions, the tumor behavior may be influenced by the BO-developmental microenvironment. Here, we describe the maturation of rat brain organoids (rBOs) into fully differentiated BOs and demonstrate their value as a model for studying glioblastoma (GB)–host interactions and their use in testing therapeutic interventions. Materials and Methods: rBOs were obtained from fetal cortical brains on the 18th day of gestation. Transcriptomic, proteomic, and metabolomic analyses determined their differentiation into maturity. Their developmental trajectory was compared to human BOs derived from induced pluripotent stem cells as well as to rat brain development. Tumor–rBO interactions, including invasion parameters and therapeutic interactions, were studied using 5 human GB models. Results: The rBOs develop into organized structures with myelinated neurons, oligodendrocytes, synapses, and glial cells, mirroring the rat brain development. GB invasion in rBOs matched those observed in orthotopic xenografts, enabling real-time assessment of invasion metrics: cellular heterogeneity, single-cell invasion speed, and tumor progression. The BOs had a strong impact on GB transcriptional activity and can be used to study therapeutic interventions. The rBO differentiation status influenced GB invasion capacity. Conclusions: The rBOs serve as an effective target brain structure for studying GB invasion parameters and for evaluating therapeutic interventions. Their rapid development into mature brain tissue makes rBOs a valuable brain avatar system for studying tumor–host interactions.

• Schoretsanitis, Georgios; Laaboub, Nermine; Crettol, Séverine; Lenk, Hasan Çağın; Bråten, Line Skute & Ranjbar, Setareh [Show all 17 contributors for this article] (2025). CYP2D6 Genotypes Do Not Affect Clozapine Levels in a Large, Multicenter Cohort: Time Has Come to Revise Food and Drug Administration’s Clozapine Packet Insert. Schizophrenia Bulletin. ISSN 0586-7614. doi: 10.1093/schbul/sbaf160. Full text in Research Archive Show summary

  Abstract Background and Hypothesis The US Food and Drug Administration (FDA) package insert for clozapine states that cytochrome P450 (CYP) 2D6 is important in clozapine metabolism, implying that CYP2D6 genotypes should be considered in clozapine dosing. We investigated differences for clozapine concentration-to-dose (C/D) ratios, as a pharmacokinetic measure, in relation to CYP2D6 phenotype. Study Design Linear mixed-effect regression models were applied to investigate the association between genotype-predicted CYP2D6 metabolizer phenotypes and C/D ratios including the effects of age, sex, smoking, and sampling time in a pooled sample of three cohorts, both without and with adjusting for the interaction between cohort and CYP2D6 phenotype, as well as in separate models stratified by cohort. Study Results We included 897 patients from three cohorts with a total of 10 428 clozapine and norclozapine measurements. We found no association between CYP2D6 phenotypes and clozapine or norclozapine C/D ratios or clozapine-to-norclozapine ratios in the pooled sample with or without adjustment for the interaction between cohort and CYP2D6 phenotype nor when analyzing three cohorts separately (P&gt;.05 in all cases). Older patients and females had higher C/D ratios of clozapine and norclozapine (P&lt;.001, P&lt;.001, P&lt;.001 and P=.02), whereas smokers had lower C/D ratios of clozapine and norclozapine as well as clozapine-to-norclozapine ratios (P&lt;.001 for all three). Conclusions We reported no association between CYP2D6 genotype-predicted phenotypes and clozapine pharmacokinetics. Dose adjustment based on CYP2D6 genotyping is unlikely to be helpful in managing clozapine-treated patients. We propose that the current FDA package insert should be updated to avoid misleading prescribers.

• Teimori, Kaveh; Larsen, Bjarke Strøm; Austli, Mathias Buaas; Nilsson, Carl Niklas; Tho, Ingunn & Nezvalova-Henriksen, Katerina (2025). Strategies for Assessing Physical Compatibility of Calcium Folinate with Bicarbonate During Methotrexate Rescue Therapy in Pediatric Patients with Acute Lymphoblastic Leukemia. Pharmaceutics. 17(9). doi: 10.3390/pharmaceutics17091155. Full text in Research Archive
• Nordby, Karoline L; Faraj, Pari; Molden, Espen & Hole, Kristine (2025). Impact of CYP2D6 genotype on fluoxetine exposure and treatment switch in adults and children/adolescents. European Journal of Clinical Pharmacology. ISSN 0031-6970. 81(11), p. 1623–1632. doi: 10.1007/s00228-025-03893-9. Full text in Research Archive
• Thorén, Linda; Lindh, Jonatan D.; Molden, Espen; Kringen, Marianne Kristiansen; Bergh, Jonas & Eliasson, Erik [Show all 7 contributors for this article] (2025). CYP2D6 genotype and outcome in tamoxifen treated early breast cancer. Acta Oncologica. ISSN 0284-186X. 64, p. 848–856. doi: 10.2340/1651-226X.2025.43208. Full text in Research Archive
• Sagedal, Solbjørg; Hovd, Markus; Åsberg, Anders; Mollnes, Tom Eirik; Klingenberg, Olav Inge & Heldal, Torbjørn Fossum [Show all 10 contributors for this article] (2025). Increased levels of ficolin-1 and of C3dg are independently associated with high risk of infection in patients with chronic kidney disease: a prospective cohort study. Frontiers in Immunology. 16. doi: 10.3389/fimmu.2025.1645347. Full text in Research Archive Show summary

  Background and hypothesis: Infection is a leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). The complement system provides crucial first-line defense against pathogens. Mannose-binding lectin (MBL), ficolins (1, 2 and 3), and collectin-LK 1 (CL-LK) are pattern recognition molecules (PRMs) of the lectin pathway (LP) that recognize microbial surfaces and activate complement. C3dg is a complement cleavage fragment indicating complement activation. The aim of the study was to investigate whether levels of PRMs and C3dg are associated with the risk of significant infections requiring hospitalization in patients with CKD. Methods: This prospective cohort study included 518 patients ≥18 years with CKD (eGFR<60 mL/min/1.73 m2), consecutively recruited between 2008-2022. About half (270/518) were in dialysis at inclusion. None of the patients were previously transplanted with any organ or stem cells. The primary endpoint was non-access-related infections requiring hospitalization. Patients were followed until kidney transplantation or death or until 31.12.2024. Plasma concentrations of the biomarkers were measured at inclusion. Time-to-event analyses using Cox regression were employed to assess associations with infection, adjusting for age, sex, diabetes, dialysis status, and dialysis vintage. Results: During a median (interquartile range [IQR]) time of follow-up of 1.24 (0.49-2.76) years, 182 patients (35%) were hospitalized due to non-access infection. Higher baseline levels of ficolin-1 and C3dg were independently associated with infection risk, HR 3.05, 95% CI 1.25-7.43, p=0.01 and HR 2.97, 95% CI 1.37-6.44, p=0.006, respectively, for each log10 unit increase. In multivariable models including all biomarkers, only C3dg remained independently associated with infection (HR 2.81, 95% CI 1.23-6.43, p=0.01). Conclusions: High levels of complement activation (C3dg) and ficolin-1 were independently associated with increased infection risk in patients with CKD. A dysregulated complement activation rather than PRM deficiency seems to be a key pathogenic mechanism resulting in increased infection risk in advanced CKD.

• Mellingsæter, Trude Cecilie; Molden, Espen & Steihaug, Ole Martin (2025). Serum Concentration of Apixaban in Relation to Renal Function in Older Hospitalized Patients. Drugs & Aging. ISSN 1170-229X. 42(9), p. 879–886. doi: 10.1007/s40266-025-01232-2. Full text in Research Archive
• Kennedy, Lauritz Hagen; Morland, Cecilie; Narum, Martine; Bergersen, Linda Hildegard & Rinholm, Johanne Egge (2025). Lactate Receptor HCAR1 Affects Axonal Development and Contributes to Lactate’s Protection of Axons and Myelin in Experimental Neonatal Hypoglycemia. eNeuro. 12(5). doi: 10.1523/eneuro.0563-24.2025. Full text in Research Archive Show summary

  Lactate plays an important role in brain energy metabolism. It contributes to normal brain development and to neuroprotection in diabetic hypoglycemia, but its role in neonatal hypoglycemia is unclear. Moreover, lactate can work as a signaling substance via the lactate receptor HCAR1 (Hydroxycarboxylic acid receptor 1). Recent studies indicate that HCAR1 is protective in mouse models of neonatal hypoxic ischemia and has a role in metabolic regulation in glial cells during hypoglycemia. Here we have studied potential impacts of HCAR1 on axonal and myelin development in the cerebral cortex and corpus callosum of young (P21) wild-type (WT) mice and HCAR1 KO mice and in cortical organotypic brain slice cultures. The HCAR1 KO mice showed lower axonal area relative to WT in both cortex and corpus callosum. However, the myelin area was unaffected by HCAR1 KO. Using particle and colocalization analysis, we show that HCAR1 KO predominantly reduces axonal size in unmyelinated axons. Using an organotypic brain slice model of neonatal hypoglycemia, we find that lactate protects both axonal and myelin development in hypoglycemia, partially via HCAR1. Lastly, live imaging with a pH-sensitive dye on acute cortical brain slices indicates that cellular lactate uptake is influenced by HCAR1. In conclusion, our findings support a role of HCAR1 in axonal development and in lactate’s protective effects in hypoglycemia.

• Nguyen, Mai Uyen T.; Neely, Michael N.; Åsberg, Anders; Boge, Craig L.K. & Downes, Kevin J. (2025). A Matched Case-Control Study to Evaluate Predicted Drug Exposures and Neutropenia during Valganciclovir Prophylaxis in Pediatric Solid Organ Transplant Recipients. Transplant Infectious Disease. ISSN 1398-2273. doi: 10.1111/tid.70146. Full text in Research Archive
• Lea, Marianne; Trapnes, Elin; Steen, Hanne & Ødegaard, Nina Bjerketveit (2025). Design and evaluation of a comprehensive training program for hospital-based clinical pharmacists - various, active, and work-integrated learning. Exploratory Research in Clinical and Social Pharmacy (ERCSP). 20. doi: 10.1016/j.rcsop.2025.100677. Full text in Research Archive
• Fløde, Mari; Hermann, Monica; Igland, Jannicke; Hernar, Ingvild; Sigurdardottir, Arun K. & Søfteland, Eirik [Show all 9 contributors for this article] (2025). Hypoglycaemia and its associations with diabetes and age-related factors in older home-dwelling people with diabetes. BMC Geriatrics. 25(1). doi: 10.1186/s12877-025-06732-9. Full text in Research Archive Show summary

  Background Studies have shown high rates of hypoglycaemia among home-dwelling older people receiving home care services. Hypoglycaemia can lead to severe consequences and in worst case, death. Therefore, knowledge about the factors associated with the occurrence of hypoglycaemia in this patient group is important. This study aimed to investigate the associations between hypoglycaemia and relevant diabetes and age-related factors among individuals with diabetes aged ≥ 65 years who received home care services. Methods This prospective observational study included data from blinded continuous glucose monitoring to identify hypoglycaemia and glycaemic variability. Further, data from blood tests (HbA1c, serum creatinine), medication lists, and questionnaires on cognitive function, functional status with need of assistance, and nutritional status were collected. Data analysis was performed using Fisher’s exact tests and unadjusted logistic regression analyses. Results In total, 56 individuals participated (52% men, median age 82 years). We identified a statistically significant association between hypoglycaemia and glycaemic variability ( p  < 0.001). All participants with a coefficient of variation (CV) ≥ 36% had undergone at least one hypoglycaemic event during the study period. Also, participants with CV ≥ 27% had higher risk of hypoglycaemia than those with CV < 27% (OR 5.3, 95% CI 1.6, 17.7). Among the 34 participants with HbA1c ≥ 53 mmol/mol, 32% experienced hypoglycaemia. In total, 93% were treated with medications that potentially interfered with the effect of their diabetes medications, and 64% were treated with medications that potentially affected their ability to detect symptoms of hypoglycaemia. The associations between hypoglycaemia and cognitive, functional, or nutritional status is uncertain due to limitations in sample size. Conclusions This study highlights a significant association between glycaemic variability and hypoglycaemia among older home-dwelling adults with diabetes receiving home care services. The prevalence of drug-drug interactions raises concerns about diabetes treatment and emphasise the need for targeted interventions to improve safety and care for this vulnerable group of patients.

• Dalmao-Fernandez, Andrea; Katare, Parmeshwar Bajirao; Bakke, Hege Gilbø; Hamarsland, Håvard; Ellefsen, Stian & Singh, Sachin [Show all 10 contributors for this article] (2025). The use of three-dimensional primary human myospheres to explore skeletal muscle effects of in vivo krill oil supplementation. In vitro models. ISSN 2731-3433. 4(2), p. 145–155. doi: 10.1007/s44164-025-00087-6. Full text in Research Archive Show summary

  Supplementation with krill oil has shown effects on whole-body lipid and glucose metabolism, as well as on skeletal muscle strength and function. We previously showed that krill oil intervention in vivo promoted fatty acid metabolism and protein synthesis in cultured human myotubes in a two-dimensional (2D) model. The aim of this study was to explore the effects of krill oil supplementation in vivo in a 3D myosphere model, and to compare a the human skeletal muscle 3D cell model to a 2D model. Myospheres were formed from myoblasts obtained before and after 7&nbsp;weeks of in vivo krill oil intervention. Glucose and oleic acid metabolism were assessed, and transcriptomic and proteomic analyses were performed. In vivo intervention with krill oil increased glucose metabolism in myospheres, while no effect was observed on fatty acid metabolism. Transcriptomic analyses of myospheres after krill oil intervention showed increased expression of genes involved in pathways like motor proteins and hypertrophy, as well as in calcium signaling, of which motor proteins and hypertrophy pathways have not been described in 2D myotube cultures. Proteomic analyses after krill oil intervention showed increased expression of proteins in glycolysis/gluconeogenesis and fatty acid degradation. Comparison of proteins expressed in the 3D myosphere model and the 2D myotube model at the basal level showed that in myospheres, mitochondrial gene expression and translation dominated, while in 2D cultures, mitochondrial organization and response to oxidative stress were more important. These findings suggest that in vivo krill oil intervention induces different metabolic effects when comparing 3D and 2D cultures. In contrast to the 2D model, data obtained with the 3D model showed gene expression changes that are more compatible with previously observed results in vivo concerning skeletal muscle motoric function. Hence, the 3D cell model might better reflect krill oil-induced modifications in skeletal muscle performance in vivo than the 2D model.

• Slørdahl, Tobias S.; Askeland, Frida Bugge; Hanssen, Margrete Sofie Sætre; Hov, Håkon; Sundt-Hansen, Stine Marie & Lindahl, Sofia [Show all 13 contributors for this article] (2025). Combined Proteasome and Autophagy Inhibition in Relapsed/Refractory Multiple Myeloma—A Phase I Trial of Hydroxychloroquine, Carfilzomib, and Dexamethasone. eJHaem. 6(1). doi: 10.1002/jha2.1091. Full text in Research Archive Show summary

  Multiple myeloma is characterized by malignant cells which produce high amounts of monoclonal immunoglobulin. Myeloma cells are, therefore, dependent on effective protein degradation. Proteasomal protein degradation is targeted by proteasome inhibitors in routine care. Autophagic protein degradation is currently not targeted in myeloma treatment. This Phase I trial showed that the combination of the proteasome inhibitor carfilzomib and the autophagy inhibitor hydroxychloroquine was well tolerated in patients with relapsed/refractory multiple myeloma. Adverse events were mostly Grades 1 and 2. An overall response rate of 44% indicates a meaningful clinical efficacy of this combination. Trial Registration : The study was registered at clinicaltrials.gov # NCT04163107.

• Hovd, Rebekka Rolfsnes; Kaupang, Åsmund; Rongved, Pål; Kildahl-Andersen, Geir; Hylland, Knut Tormodssønn & Hovland, Ragnar [Show all 9 contributors for this article] (2025). APC24-7, a covalent combination of boronic acid and chelator moieties, restores β-lactam efficiency against metallo-β-lactamase-producers. mSphere. 10(12). doi: 10.1128/msphere.00418-25. Full text in Research Archive Show summary

  β-Lactam/β-lactamase inhibitor combinations have significantly improved treatment outcomes for infections caused by serine β-lactamase (SBL)-producing pathogens. However, the continued emergence and spread of metallo-β-lactamases (MBLs), for which no clinically approved inhibitors currently exist, poses a serious threat to the long-term effectiveness of β-lactam-based therapies. To bridge this therapeutic gap, the boronic acid transition state analog, taniborbactam (Venatorx Pharmaceuticals), was developed, targeting SBLs and widespread MBLs such as NDM-1 and VIM-2. However, taniborbactam-escape variants have been detected among various MBL enzymes, including members of the NDM and IMP families. Here, we explored whether covalently combining two complementary inhibitor structures, a boronic acid transition state analog and a dipicolyl ethylenediamine-based metal chelator, can restore β-lactam susceptibility in MBL-producing bacterial strains, including taniborbactam-escape variants. APC24-7 successfully sensitized clinical isolates of SBL- and MBL-producing Klebsiella pneumoniae and Escherichia coli to meropenem. While APC24-7 demonstrated similarities in resensitization behavior to taniborbactam against a wide range of isogenic E. coli expressing single SBLs, APC24-7 reversed NDM-9- or IMP-26-mediated meropenem resistance more efficiently. To investigate the potential role of the chelator motif in the MBL inhibition of APC24-7, susceptibility tests were conducted with an excess of exogenous Zn² + . APC24-7-mediated resensitization remained unaffected in the presence of Zn² + for strains producing NDM-1 and VIM-2. However, its ability to reverse NDM-9- and IMP-26-mediated meropenem resistance was attenuated upon Zn² + supplementation. These findings demonstrate that combining functionally complementary chemical structures, such as chelators and boronic acids, can aid in expanding the resensitization ability of existing β-lactamase inhibitors. IMPORTANCE The ability of bacteria such as Klebsiella pneumoniae and Escherichia coli to circumvent antimicrobial chemotherapy has become a global public health crisis. The high prevalence of β-lactamase enzymes capable of rendering our most prescribed antibiotics, the β-lactams (BLs) inactive, has left us with few available treatment options against infections caused by these bacteria. The use of small molecules that inhibit especially serine β-lactamases has substantially prolonged the lifetime of BL antibiotics. Yet, most clinically available inhibitors either do not possess or have limited ability to reverse resistance conferred by metallo-β-lactamase (MBL) enzymes. Combining chelator and transition state analog technology, our hybrid compound restores the effectiveness of BL antibiotics in cases of resistance conferred by both serine β-lactamases (SBLs) and MBLs. Our approach of covalently combining a chelator with an existing SBL inhibitor scaffold offers a promising solution for managing life-threatening infections and prolonging the use of clinically available BLs.

• Wojewodzic, Marcin Wlodzimierz; L.D., Volders, Ellen; Coby, Meijer,; Grotmol, Tom; J., Touw, Daan & Sjoukje, Lubberts, [Show all 9 contributors for this article] (2025). Changes in methylation associated with development of metabolic syndrome in testicular cancer patients treated with cisplatin chemotherapy. Scientific Reports. 15. doi: 10.1038/s41598-025-22918-y. Full text in Research Archive Show summary

  Patients with metastatic testicular cancer (TC) treated with cisplatin-based chemotherapy (CBCT) are prone to develop metabolic syndrome (MetS). In an epigenome wide association study in patients with TC we have shown that DNA methylation was associated to CBCT. The aim of the study was to investigate whether there was a change in DNA methylation after treatment with CBCT, and if methylation status is related to the presence or development of MetS. In a prospective cohort of 67 TC patients who received CBCT, we assessed whole blood global methylation long interspersed nuclear element-1 (LINE-1) and DNA methylation at selected cytosine-phosphate-guanine dinucleotide (CpG) sites associated with MetS using targeted sequencing. Measured samples were taken before, one month after, and one year after CBCT. Development of MetS was assessed before and up to five years after CBCT. Serum platinum levels were measured to assess platinum exposure (PtAUC) within the first year after the start of CBCT. Data were used for paired comparisons, comparisons between groups, statistical modeling to account for covariates, and machine learning approaches to predict occurrence of MetS five years after diagnosis. Global methylation did not change during the first year after the start of CBCT (median 73.7% (25th -75th percentile 72.0–75.2) vs. 73.9% (72.5–75.1)). Seven out of the 16 other selected CpGs decreased. Patients with MetS before start of CBCT (N = 18) showed a larger decrease than patients without MetS (N = 49) for AC090023 (-11.6% vs. -8.2%, p = 0.008), NCAM2 (-6.5% vs. -1.6%, p = 0.030), and TOM1L2 (-5.8% vs. -2.6%, p = 0.003). The 15 patients who did not have MetS prior to CBCT, but developed MetS within five years after treatment showed an increase in global methylation (1.5% vs. − 0.6%, p = 0.008) after one year, and a decrease in TOM1L2 methylation (-4.0% vs. -1.6%, p = 0.015) when compared to patients who did not have prior to CBCT nor developed MetS (N = 34). There was no difference in PtAUC during the first year after the start of CBCT between the latter groups (70.0 vs. 67.9 days*mg/L, p = 0.206). Changes in global DNA methylation and TOM1L2 one year after the start of CBCT are associated with a higher risk for newly developing MetS within five years. This may indicate potential for tailored advice, based on epigenetic status, to patients treated with chemotherapy for TC to prevent development of MetS.

• Mueller, Michael; Blandino, Alice; Scherer, Dominique; Zulantay, Inés; Apt, Werner & Varela, Nelson M. [Show all 18 contributors for this article] (2025). Small-RNA sequencing identifies serum microRNAs associated with abnormal electrocardiography findings in patients with Chagas disease. Journal of Infection. ISSN 0163-4453. 91(4). doi: 10.1016/j.jinf.2025.106613. Full text in Research Archive
• Folkestad, Oddry H; Sponheim, Jon; Åvitsland, Tone Lise; Mordal, Kjerstin Elisabeth Skrede; Vethe, Nils Tore & Thiis-Evensen, Espen (2025). The relationship between dose, concentration and toxicity of everolimus in the treatment of neuroendocrine tumors: A prospective observational study. Journal of Neuroendocrinology (JNE). ISSN 0953-8194. 38(1). doi: 10.1111/jne.70107. Full text in Research Archive Show summary

  Abstract Everolimus is used in the treatment of patients with advanced neuroendocrine tumors (NET) and is administered at fixed doses despite known interpatient pharmacokinetic variability. This may affect both efficacy and tolerability. We wanted to investigate the relationship between prescribed dose, blood trough concentrations ( C trough ), and toxicity in NET patients receiving everolimus in routine clinical practice. In this prospective observational study NET patients were treated with everolimus, mostly as third‐ or fourth‐line therapy. Dose was adjusted according to adverse effects and tumor response. Concentrations ( C trough ) of everolimus were measured at each routine follow‐up and correlated to dose and cumulative adverse event (cAE) scores. Associations were evaluated using linear and generalized linear mixed models which accounted for repeated measurements within patients and varying dose regimens over time. Thirty‐six patients were included. Everolimus dose was a significant predictor of C trough ( p  < .001), but considerable interindividual variability was observed. Median C trough levels increased with dose: 3.9, 5.1, 7.4, and 16.4 ng/mL for 2.5, 5.0, 7.5, and 10.0 mg per day, respectively. Considerable overlap in blood concentration was observed across dose groups; patients receiving 2.5 mg reached levels as high as 8.6 ng/mL, while those on 5 mg exhibited a wide range from 1.1 to 21.2 ng/mL. C trough ≥ 6.0 ng/mL was associated with increased toxicity ( p  = .03), whereas nominal dose was not a reliable independent predictor of adverse events. Although median blood concentrations increased with higher doses, there was considerable variation between patients, resulting in overlapping concentration ranges across all dose groups. This indicates that fixed‐dose regimens may not reliably predict systemic drug exposure. Everolimus blood concentrations were superior to dose levels in predicting adverse events. Therapeutic drug monitoring and individualized dose adjustment may improve the balance between efficacy and toxicity in NET patients treated with everolimus.

• Pestarino, Luca; Fortner, Shannon Renee Turzanski; Nøst, Therese Haugdahl; Fotopoulos, Ioannis; Urbarova, Ilona H. & Røe, Oluf Dimitri [Show all 8 contributors for this article] (2025). Recommendations for Validating Omics Prediction Models: Insights from a Lung Cancer RNA Biomarker Study. Cancer Epidemiology, Biomarkers and Prevention. ISSN 1055-9965. 34(10), p. 1852–1860. doi: 10.1158/1055-9965.epi-25-0787. Full text in Research Archive Show summary

  Background: External validation of predictive models in medical research is crucial to ensure their generalizability and applicability across diverse populations. However, validation often reveals discrepancies in model performance due to cohort differences, sample collection and storage, overfitting, and inconsistencies in data handling. This study investigates the challenges encountered during external validation of predictive models for early lung cancer detection using small RNA biomarkers, tying these challenges to specific validation outcomes and deriving recommendations. Methods: Predictive models based on the XGBoost algorithm, developed from serum samples in the JanusRNA cohort, were externally validated in two independent Norwegian cohorts: HUNT and Norwegian Women and Cancer Study. These cohorts differed in sample types, RNA abundance, library preparation protocols, and lung cancer histologic classification. Strategies to harmonize data processing and address these discrepancies were used to ensure a robust validation process. Results: Validation revealed significant challenges due to cohort heterogeneity. Median AUC values ranged from 0.50 to 0.66 in validation cohorts, compared with 0.62 to 0.76 in the original models. Models performed worse in the female-only Norwegian Women and Cancer Study cohort, in which plasma was used, highlighting the impact of sample type and cohort characteristics on predictive accuracy. Conclusion: Based on the challenges encountered during validation, we propose seven recommendations to guide robust external validation of omics-based predictive models, including harmonizing data processing across cohorts, reevaluating overfitting, and critically assessing model performance for clinical applications. Impact: By highlighting practical issues in model validation and providing recommendations, this study supports more reliable and clinically applicable biomarker-based prediction models, ultimately aiding cancer screening and prevention efforts.

• Noordzij, Hanna Theodora; Wortel, Meike Tessa; Heintz-Buschart, Anna; Petrikonyte, Patricija; Muinck, Eric de & Trosvik, Pål (2025). Assembly-based analysis of the infant gut microbiome reveals novel ubiquitous plasmids. Plasmid. ISSN 0147-619X. 134, p. 1–15. doi: 10.1016/j.plasmid.2025.102761. Full text in Research Archive Show summary

  Little is known about the role of mobile genetic elements in natural ecosystems such as the infant gut microbiome. Here, we conduct the most comprehensive longitudinal study of the infant plasmidome to date by analyzing monthly fecal samples from 12 infants from birth to one year of age. We employ an assembly-based bioinformatic pipeline for the reconstruction and identification of full-length plasmids, including a novel approach for assigning putative plasmid hosts. We then investigated plasmid content and dynamics in the infant gut microbiome. After assembly and identification, we identified 620 unique circular plasmids in the infant cohort, including a number of novel sequences. Independent assembly of the same plasmids in several samples and infants helped corroborate the authenticity of the plasmids. Among the observed plasmids was the recently described ubiquitous and abundant Bacteroides plasmid pBI143. Overall, the genus Bacteroides had the highest plasmid carriage, while the highest plasmid diversity was observed in Clostridium, including 5 previously unknown widespread plasmids. Lastly, we leveraged the longitudinal nature of our dataset to investigate contemporaneous correlations between temporal variations in plasmid abundances and species dynamics. This enabled us to link co-residing plasmids and tightly linked plasmid-taxon pairs within each infant. These insights into plasmid ecology help us understand determinants driving plasmid distribution in complex microbial communities.

• Vevik, Kristina; Sribasgaran, Biramitha; Cai, Kun; Naemi, Ali-Oddin; Kaspersen, Håkon & Uhlig, Silvio [Show all 8 contributors for this article] (2025). TrkA of Streptococcus mitis CCUG31611 binds cyclic di-adenosine monophosphate and is required for growth in low potassium conditions. Microbiology (Reading). ISSN 1350-0872. 171(8). doi: 10.1099/mic.0.001597. Full text in Research Archive Show summary

  Cyclic di-adenosine monophosphate (c-di-AMP) is a bacterial second messenger regulating many physiological processes in bacteria. In the oral commensal species Streptococcus mitis, c-di-AMP is involved in regulating metabolism, growth, colony morphology, chain length, biofilm formation and DNA stress tolerance. However, no c-di-AMP-regulated effector proteins have yet been characterized in S. mitis. In this study, we first show that a ΔcdaA mutant, unable to produce c-di-AMP, grows slowly under low environmental potassium conditions. Growth of the cdaA mutant was not restored by reintroducing cdaA in the original locus (KBcdaA). Whole-genome sequencing of multiple KBcdaA isolates revealed secondary mutations in a putative potassium transporter. The mutations were predicted to result in the truncation of the protein or the alteration of a conserved glycine residue essential for selective potassium uptake, disrupting protein function. A Δpde2 mutant overproducing c-di-AMP survived poorly under high environmental sodium concentrations. We then characterized the potassium transporter regulator protein TrkA. Biochemical analyses of the purified recombinant TrkA protein revealed that it specifically binds c-di-AMP with high affinity in vitro. Using deletion mutants of trkA, we demonstrate that TrkA is essential for growth under low environmental potassium conditions. Ultra-high-performance liquid chromatography coupled to tandem mass spectrometry revealed lower c-di-AMP concentration in the ΔtrkA mutant compared to the WT. This was not due to transcriptional regulation of the expression of the c-di-AMP turnover proteins CdaA, Pde1 or Pde2. C-di-AMP production is not affected by the extracellular potassium concentrations under the conditions tested. We also demonstrate a potential role of TrkA in UV stress tolerance but do not characterize the mechanism in this study.

• Arabaci, Öyküm Kaplan; Zosen, Denis; Domanska, Diana; Bjørnstad, Sigrid; Santini, Simone & Karaca, Umut [Show all 12 contributors for this article] (2025). The antidepressant venlafaxine induces upregulation of miR-92 and histological alterations in a chicken embryo model. Neurochemistry International. ISSN 0197-0186. 190, p. 1–11. doi: 10.1016/j.neuint.2025.106056. Full text in Research Archive Show summary

  Antidepressants are commonly prescribed for treating anxiety disorders and depression, including pregnant patients. These medications influence the absorption and metabolism of key neurotransmitters such as serotonin, norepinephrine, and dopamine. However, many aspects of antidepressant function remain unclear, especially regarding their impact on neurodevelopment when used during pregnancy. To explore this, we employed a 3R-friendly chicken embryo model to investigate the cellular and molecular implications of antidepressants use. We focused on commonly used antidepressants for the study: escitalopram, which is a selective serotonin reuptake inhibitor; and venlafaxine, a serotonin and noradrenaline reuptake inhibitor, both of which are frequently prescribed during pregnancy. Drug distribution analysis showed that both antidepressant drugs reached clinical concentrations in the brain of developing chicken embryos and persisted for several hours. High-throughput miRNA-sequencing showed that venlafaxine upregulated 13 different miRNAs in the chicken cerebellum. Specifically, miR-92 and its human ortholog, miR-363, were significantly upregulated in chicken cerebellum and neuronally differentiated human SH-SY5Y cells, respectively. Neurite metrics showed a significant reduction in neurite outgrowth with venlafaxine, but not with escitalopram. Furthermore, venlafaxine caused histological alterations, such as increased white matter and reduced thickness of the cortical and molecular layer in the cerebellum. Both drugs reduced the thickness of the external granular layer and the number of mitotic events, impacting this crucial germinal zone of the brain. These findings highlight distinct neurodevelopmental effects of escitalopram and venlafaxine and raise awareness for potential adverse neurological effects in offspring exposed to antidepressants in utero.

• Munkhaugen, John; Kristensen, Anna Meta D.; Halvorsen, Sigrun; Holmager, Therese; Olsen, Michael Hecht & Bakken, Arnhild [Show all 64 contributors for this article] (2025). Beta-Blockers after Myocardial Infarction in Patients without Heart Failure. New England Journal of Medicine. ISSN 0028-4793. 393(19), p. 1901–1911. doi: 10.1056/nejmoa2505985. Full text in Research Archive Show summary

  Background: The evidence supporting beta-blocker therapy after myocardial infarction was established before the introduction of modern coronary reperfusion therapy and secondary prevention strategies. Methods: In an open-label, randomized trial with blinded end-point evaluation, conducted in Denmark and Norway, we assigned patients who had had a myocardial infarction and who had a left ventricular ejection fraction of at least 40%, in a 1:1 ratio, to receive long-term beta-blocker therapy within 14 days after the event or no beta-blocker therapy. The primary end point was a composite of death from any cause or major adverse cardiovascular events (new myocardial infarction, unplanned coronary revascularization, ischemic stroke, heart failure, or malignant ventricular arrhythmias). Results: A total of 5574 patients underwent randomization and were included in the main analyses - 2783 in the beta-blocker group and 2791 in the no-beta-blocker group. After a median follow-up of 3.5 years (interquartile range, 2.2 to 4.6), a primary end-point event had occurred in 394 patients (14.2%) in the beta-blocker group and in 454 patients (16.3%) in the no-beta-blocker group (hazard ratio, 0.85; 95% confidence interval [CI], 0.75 to 0.98; P = 0.03). Death from any cause occurred in 4.2% of the patients in the beta-blocker group and in 4.4% of those in the no-beta-blocker group; myocardial infarction occurred in 5.0% and 6.7%, respectively (hazard ratio, 0.73; 95% CI, 0.59 to 0.92), unplanned coronary revascularization in 3.9% and 3.9%, ischemic stroke in 1.6% and 1.3%, heart failure in 1.5% and 1.9%, and malignant ventricular arrhythmias in 0.5% and 0.6%. No apparent differences in safety outcomes were observed between the groups. Conclusions: Among patients with a myocardial infarction and a left ventricular ejection fraction of at least 40%, beta-blocker therapy led to a lower risk of death or major adverse cardiovascular events than no beta-blocker therapy

• Nundal, Camilla Hatlevoll; Lunde, Siri; Bakke, Hege Gilbø; Bohov, Pavol; Aloysius, Thomas Aquinas & Rustan, Arild Christian [Show all 15 contributors for this article] (2025). Herring oil rich in long-chain monounsaturated fatty acid (C22: 1n-11) lowers plasma lipids and modulates fatty acid composition, oxidation, and inflammation in rats. Frontiers in Nutrition. 12, p. 1–11. doi: 10.3389/fnut.2025.1611166. Full text in Research Archive Show summary

  Introduction: Marine oils and fatty fish rich in long-chain n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (C20:5n-3, EPA) and docosahexaenoic acid (C22:6n-3, DHA), have been reported to enhance fatty acid (FA) oxidation and reduce plasma triacylglycerol and cholesterol levels. In addition to n-3 PUFAs, herring oil contains long-chain monounsaturated fatty acids (MUFAs), including cetoleic acid (C22:1n-11). This study aimed to investigate the effect of consuming CETO3® oil—derived from herring and naturally rich in n-3 PUFAs and cetoleic acid—on plasma lipid levels, FA composition, mitochondrial oxidation, and inflammation in rats. Methods: Rats were fed low-fat diets supplemented with 5% CETO3® oil (experimental) or soy oil (control) for 10 weeks. Plasma lipid profile (triglycerides (TG), total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL)) and FA composition in both liver and plasma were analyzed. In vitro substrate oxidation was assessed using ¹⁴CO₂-trapping in human liver and human myotubes. Safety parameters, including blood hematology, glucose tolerance, and organ weights, were also measured. Results: CETO3® supplementation decreased plasma levels of total fat (−58%), TG (−55%), total cholesterol (−41%), and LDL cholesterol (−45%), while increasing the ratio of HDL to LDL cholesterol (46%). Supplementation also increased hepatic and plasma levels of long-chain n-3, n-9, and n-11 MUFAs, including C22:1n-11, and decreased n-6 FA accumulation. The reduction in saturated long-chain FAs in both the liver and plasma indicated increased hepatic peroxisomal and mitochondrial activity. Furthermore, increased oleic acid oxidation was observed in human myotubes in the presence of C20:1n-11 and C20:1n-9. Discussion: These findings suggest that intake of CETO3® oil lowers plasma lipids, potentially through enhanced peroxisomal and mitochondrial FA oxidation. The shift in FA composition, with reduced n-6 FAs and increased n-3 and n-11 MUFAs, indicates an anti-inflammatory effect. CETO3® oil also appears safe, as hematological parameters, glucose tolerance, and organ weights remained unaffected.

• Kamenova, Stefaniya Kamenova; Albon, Steve D.; Loe, Leif Egil; Irvine, R. Justin; Langvatn, Rolf & Gusarova, Galina [Show all 8 contributors for this article] (2025). Arctic Greening Drives Changes in the Diet and Gut Microbiome of a Large Herbivore With Consequences for Body Mass. Ecology and Evolution. 15(7). doi: 10.1002/ece3.71731. Full text in Research Archive Show summary

  Rapid climate warming is ‘greening’ the tundra, reflecting a higher plant biomass, particularly of deciduous shrubs and grasses. However, the consequences of these changes for herbivore nutrition are unclear. Although, the gut microbiome mediates nutrient metabolism, and hence herbivores' capacity to adapt to dietary change, few studies have investigated the effect of annual changes in the diet-gut microbiome nexus on fitness-related traits. In a model system, the Svalbard reindeer, a species experiencing the greatest rate of climate warming on Earth, we investigate how changes in diet and the gut microbiome impact reindeer body mass. Using high-resolution DNA metabarcoding, we assessed diet and gut microbiome bacterial composition in rumen samples from animals culled in October from 1998 to 2004 in four different valleys. Overall diet diversity and grass relative reads abundance (RRA) were significantly higher following warmer summers, while the RRA of the dwarf shrub Salix polaris increased with the maximum normalised difference vegetation index (NDVI), our measure of annual biomass. Autumn body mass, a strong proxy of fitness in Svalbard reindeer, was significantly, positively correlated with Salix RRA, most pronounced in females that had reproduced, and by that depleted body reserves. Multivariate analyses revealed a highly significant relationship between diet and microbiome composition at the individual level. This included a significant positive correlation between Salix and bacterial diversity. However, a structural equation model revealed that the direct path effect of Salix on reindeer body mass was stronger than the indirect path effect, mediated through the gut microbiome. Our results suggest that climate-driven Arctic greening may have implications for herbivore body mass, operating through a change in diet composition. These findings reveal some of the mechanistic underpinnings of Arctic warming on herbivore populations and highlight the importance of the diet−gut microbiome nexus in facilitating species resilience to rapid climate change.

• Smith, Robert Løvsletten; Andreassen, Ole; Kane, John M.; Schoretsanitis, Georgios & Molden, Espen (2025). Correlation Between Clozapine and CRP Levels in Relation to Smoking Status. Acta Psychiatrica Scandinavica. ISSN 0001-690X. 152(1), p. 69–76. doi: 10.1111/acps.13801. Full text in Research Archive
• Turewicz, Michael; Skagen, Christine; Hartwig, Sonja; Majda, Stephan; Thedinga, Kristina & Herwig, Ralf [Show all 18 contributors for this article] (2025). Temporal phosphoproteomics reveals circuitry of phased propagation in insulin signaling. Nature Communications. 16(1). doi: 10.1038/s41467-025-56335-6. Full text in Research Archive Show summary

  Insulin is a pleiotropic hormone that elicits its metabolic and mitogenic actions through numerous rapid and reversible protein phosphorylations. The temporal regulation of insulin’s intracellular signaling cascade is highly complex and insufficiently understood. We conduct a time-resolved analysis of the global insulin-regulated phosphoproteome of differentiated human primary myotubes derived from satellite cells of healthy donors using high-resolution mass spectrometry. Identification and tracking of ~13,000 phosphopeptides over time reveal a highly complex and coordinated network of transient phosphorylation and dephosphorylation events that can be allocated to time-phased regulation of distinct and non-overlapping subcellular pathways. Advanced network analysis combining protein-protein-interaction (PPI) resources and investigation of donor variability in relative phosphosite occupancy over time identifies novel putative candidates in non-canonical insulin signaling and key regulatory nodes that are likely essential for signal propagation. Lastly, we find that insulin-regulated phosphorylation of the pre-catalytic spliceosome complex is associated with acute alternative splicing events in the transcriptome of human skeletal muscle. Our findings highlight the temporal relevance of protein phosphorylations and suggest that synchronized contributions of multiple signaling pathways form part of the circuitry for propagating information to insulin effector sites.

• Velle, Gaute; Thorstad, Eva Bonsak; Garseth, Åse Helen; Gjøen, Tor; Gulla, Snorre & Lo, Håvard [Show all 8 contributors for this article] (2025). Balancing the restoration of a native fish and the risks of hitchhiking invasive species. Management of Biological Invasions. ISSN 1989-8649. 16(1), p. 247–276. doi: 10.3391/MBI.2025.16.1.15. Full text in Research Archive Show summary

  Reintroducing a species to an area where it is locally extinct may contribute to reestablishing the ecosystem. However, we show that such reintroductions can pose a risk to biodiversity by introducing hitchhiking invasive organisms together with the donor population. This risk was caused by more severe impacts of invasive organisms in the habitat of the donor population than the receiving environment. The freshwater resident Atlantic salmon (Salmo salar) in Sweden’s River Klarälven perform feeding migrations to Lake Vänern. The upper part of the watershed, in Norway, lost its salmon population due to hydropower development that obstructed upstream migration. We conducted a risk assessment of the potential impacts on native ecosystems from invasive organisms associated with reintroducing Atlantic salmon into the Norwegian part of the watershed by importing adult salmon spawners. This assessment is crucial due to differences in the development of invasive organisms in the Swedish and Norwegian parts of the watershed. The risk of impacts was evaluated for invasive species, parasites, bacterial pathogens, and viruses that are present or likely present in the lower part of the watershed, or at risk of being introduced. We found a high risk of negative impacts associated with the parasite Gyrodactylus salaris, viral hemorrhagic septicemia virus (VHSV), Aphanomyces astaci causing crayfish plague, Renibacterium salmoninarum causing bacterial kidney disease, and Tetracapsuloides bryosalmonae causing proliferative kidney disease. In addition, 20 invasive species and pathogens were associated with a medium risk and three with a low risk. The case study contributes to a deeper understanding of how reestablishing locally extinct or diminished species can influence biodiversity conservation efforts and the health of aquatic ecosystems, underlining the importance of comprehensive planning in restoration projects. We highlight the importance of risk assessment of invasive species when considering the reintroduction of native species or dam removal. environmental risk assessment, non-native species, species reintroduction, pathogens, landlocked Atlantic salmon, biological conservation, dam removal

• Drevland, Ole Martin; Skadberg, Eline Supannee Setu; Tran, Lan Anh; Åsberg, Anders; Midtvedt, Karsten & Robertsen, Ida (2025). Development and Clinical Validation of a Volumetric Absorptive Capillary Microsampling Method for Quantification of Mycophenolic Acid and Mycophenolic Acid Glucuronide in Kidney Transplant Recipients. Therapeutic Drug Monitoring. ISSN 0163-4356. 47(6), p. 790–798. doi: 10.1097/FTD.0000000000001330. Full text in Research Archive
• Gopalakrishnan, Vancheswaran; Kumar, Chanchal; Robertsen, Ida; Morehouse, Christopher; Sparklin, Ben & Khader, Shameer [Show all 19 contributors for this article] (2025). A multi-omics microbiome signature is associated with the benefits of gastric bypass surgery and is differentiated from diet induced weight loss through 2 years of follow-up. Mucosal Immunology. ISSN 1933-0219. 18(4), p. 825–835. doi: 10.1016/j.mucimm.2025.04.002. Full text in Research Archive Show summary

  Roux-en-Y gastric bypass (GBP) surgery is an effective treatment for reducing body weight and correcting metabolic dysfunction in individuals with severe obesity. Herein, we characterize the differences between very low energy diet (VLED) and GBP induced weight loss by multi-omic analyses of microbiome and host features in a non-randomized, controlled, single-center study. Eighty-eight participants with severe obesity were recruited into two arms – GBP versus VLED with matching weight loss for 6 weeks and 2-years of follow-up. A dramatic shift in the distribution of gut microbial taxa and their functional capacity was seen in the GBP group at Week 2 after surgery and was sustained through 2 years. Multi-omic analyses were performed after 6 weeks of matching weight loss between the GBP and VLED groups, which pointed to microbiome derived metabolites such as indoxyl sulphate as characterizing the GBP group. We also identified an inverse association between Streptococcus parasanguinis (an oral commensal) and plasma levels of tryptophan and tyrosine. These data have important implications, as they reveal a significant robust restructuring of the microbiome away from a baseline dysbiotic state in the GBP group. Furthermore, multi-omics modelling points to potentially novel mechanistic insights at the intersection of the microbiome and host.

• O'Connell, Kevin Sean; Koromina, Maria; Veen, Tracy van der; Boltz, Toni; David, Friederike S. & Yang, Jessica Mei Kay [Show all 313 contributors for this article] (2025). Genomics yields biological and phenotypic insights into bipolar disorder. Nature. ISSN 0028-0836. 639, p. 968–975. doi: 10.1038/s41586-024-08468-9. Full text in Research Archive Show summary

  Bipolar disorder is a leading contributor to the global burden of disease1. Despite high heritability (60–80%), the majority of the underlying genetic determinants remain unknown2. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.8 million controls), combining clinical, community and self-reported samples. We identified 298 genome-wide significant loci in the multi-ancestry meta-analysis, a fourfold increase over previous findings3, and identified an ancestry-specific association in the East Asian cohort. Integrating results from fine-mapping and other variant-to-gene mapping approaches identified 36 credible genes in the aetiology of bipolar disorder. Genes prioritized through fine-mapping were enriched for ultra-rare damaging missense and protein-truncating variations in cases with bipolar disorder4, highlighting convergence of common and rare variant signals. We report differences in the genetic architecture of bipolar disorder depending on the source of patient ascertainment and on bipolar disorder subtype (type I or type II). Several analyses implicate specific cell types in the pathophysiology of bipolar disorder, including GABAergic interneurons and medium spiny neurons. Together, these analyses provide additional insights into the genetic architecture and biological underpinnings of bipolar disorder.

• Nyberg, Henriette Eckhardt; Bogen, Inger Lise; Duale, Nur & Andersen, Jannike Mørch (2025). Prenatal exposure to methadone or buprenorphine alters transcriptional networks associated with synaptic signaling in newborn rats. Neuropharmacology. ISSN 0028-3908. 270. doi: 10.1016/j.neuropharm.2025.110368. Full text in Research Archive
• Johansson, Inger; Xanthopoulou, Emmanouella M.; Zhou, Yitian; Sanchez-Spitman, Anabel; Lee, Maaike van der & Wollmann, Birgit Malene Tovik [Show all 12 contributors for this article] (2025). Improved Prediction of CYP2D6 Catalyzed Drug Metabolism by Taking Variant Substrate Specificities and Novel Polymorphic Haplotypes into Account. Clinical Pharmacology and Therapeutics. ISSN 0009-9236. 118(1), p. 218–231. doi: 10.1002/cpt.3680. Full text in Research Archive Show summary

  The polymorphic CYP2D6 enzyme plays a pivotal role in the metabolism of approximately 25% of clinically prescribed drugs. However, the impact of specific genetic variants on the interindividual variability in CYP2D6-mediated drug metabolism remains insufficiently quantified. This translational study sought to address this gap by analyzing the genotypes and phenotypes of patients in two large clinical cohorts, focusing on the metabolism of the CYP2D6 substrates risperidone and desmethyltamoxifen. The analysis incorporated novel polymorphic haplotypes and substrate-specific differences among the CYP2D6.1, CYP2D6.2, and CYP2D6.35 enzyme variants. The study revealed that CYP2D6.2 and CYP2D6.35 exhibit reduced metabolic capacity for these substrates, both in vivo and in an in vitro expression model. This was evidenced by decreased catalytic turnover (Kcat), decreased substrate affinity, and altered substrate docking. Furthermore, novel polymorphic haplotypes on the CYP2D6*1, CYP2D6*2, and CYP2D6*35 backgrounds were identified, each associated with a 30–40% increase in CYP2D6 activity. Incorporating these findings into prediction equations significantly improved the genetic prediction accuracy (R2) for CYP2D6-mediated metabolism of desmethyltamoxifen from 59% to 71% and risperidone, also metabolized by CYP3A4, from 42% to 46%. These results highlight the importance of accounting for drug-specific interactions with enzyme variants and integrating distinct polymorphic haplotypes into CYP pharmacogenomic models and guidelines for better translation into clinical practice.

• Katare, Parmeshwar Bajirao; Tingstad, Ragna Husby; Beajani, Siver; Indseth, Jørgen Pasjkurov; Telle-Hansen, Vibeke & Myhrstad, Mari Charlotte Wik [Show all 10 contributors for this article] (2025). Divergent effects of monomethyl branched-chain fatty acids on energy metabolism and insulin signaling in human myotubes. Journal of Lipid Research. ISSN 0022-2275. 66(3), p. 1–12. doi: 10.1016/j.jlr.2025.100764. Full text in Research Archive Show summary

  Branched-chain fatty acids (BCFAs) are predominantly saturated fatty acids with one or more methyl branches on the carbon chain, typically found in dairy products and measured in micromolar concentrations in human plasma. The biological function of BCFAs in humans remains ill-defined, but a relationship between circulating BCFAs and cardiometabolic health has been suggested. The objective of this study was to evaluate the impact of BCFAs on energy metabolism in human myotubes. The results revealed distinct effects of BCFAs. 12-Methyltetradecanoic acid (12-MTD) increased glucose uptake and glycogen synthesis, while 13-methyltetradecanoic acid (13-MTD), 14-methylhexadecanoic acid (14-MHD), and 15-methylhexadecanoic acid (15-MHD) increased oleic acid uptake and 13-MTD and 15-MHD oleic acid oxidation, indicating a more general stimulatory effect on fatty acid than glucose metabolism. Interestingly, the same BCFAs, 13-MTD, 14-MHD, and 15-MHD, appeared to reduce insulin-stimulated glycogen synthesis. Insulin-stimulated phosphorylation of IRS1 was not apparent after exposure to 12-MTD, 13-MTD, and 15-MHD, whereas insulin-stimulated phosphorylation of Akt was unchanged by BCFAs. Incorporation of [14C]leucine into lipids was affected, as 13-MTD increased the total lipid content, and 12-MTD altered the distribution of lipid classes. Metabolic flux analysis indicated that 14-MHD stimulated extracellular acidification. The effects of BCFAs might involve increased mRNA expression of pyruvate dehydrogenase kinase 4. In conclusion, the study demonstrates that different BCFAs have distinct effects on energy metabolism in myotubes, 12-MTD mainly affect glucose metabolism, while 13-MTD, 14-MHD, and 15-MHD modulated oleic acid metabolism. These data suggest that some BCFAs might have therapeutic applications by improving energy metabolism

• Holmlund, Ingrid; Ahmadi, Samira; Ruyter, Bente Synnøve; Østbye, Tone-Kari K; Bou, Marta & Gjøen, Tor (2025). Effect of eicosapentaenoic acid on innate immune responses in Atlantic salmon cells infected with infectious salmon anemia virus. Virology Journal. 22(1), p. 1–15. doi: 10.1186/s12985-024-02619-0. Full text in Research Archive Show summary

  Aquaculture is one of the world's fastest-growing sectors in food production but with multiple challenges related to animal handling and infections. The disease caused by infectious salmon anemia virus (ISAV) leads to outbreaks of local epidemics, reducing animal welfare, and causing significant economic losses. The composition of feed has shifted from marine ingredients such as fish oil and fish meal towards a more plant-based diet causing reduced levels of eicosapentaenoic acid (EPA). The aim of this study was to investigate whether low or high levels of EPA affect the expression of genes related to the innate immune response 48 h after infection with ISAV. The study includes seven experimental groups: ± ISAV and various levels of EPA up to 200 µM. Analysis of RNA sequencing data showed that more than 3000 genes were affected by ISAV alone (without additional EPA). In cells with increasing levels of EPA, more than 2500 additional genes were differentially expressed. This indicates that high levels of EPA concentration have an independent effect on gene expression in virus-infected cells, not observed at lower levels of EPA. Analyses of enriched biological processes and molecular functions (GO and KEGG analysis) revealed that EPA had a limited impact on the innate immune system alone, but that many processes were affected by EPA when cells were virus infected. Several biological pathways were affected, including protein synthesis (ribosomal transcripts), peroxisome proliferator activated receptor (PPAR) signaling, and ferroptosis. Cells exposed to both increasing concentrations of EPA and virus displayed gene expression patterns indicating increased formation of oxygen radicals and that cell death via ferroptosis was activated. This gene expression pattern was not observed during infection at low EPA levels or when Atlantic salmon kidney (ASK) cells were exposed to the highest EPA level (200 μM) without virus infection. Cell death via ferroptosis may therefore be a mechanism for controlled cell death and thus reduction of virus replication when there are enough polyunsaturated fatty acids (PUFAs) in the membrane.

• Heldal, Torbjørn Fossum; Åsberg, Anders; Ueland, Thor; Reisæter, Anna Varberg; Pischke, Soeren & Mollnes, Tom Eirik [Show all 11 contributors for this article] (2025). Systemic inflammation is an important risk factor and predictor of graft loss and mortality one year after kidney transplantation. Frontiers in Immunology. 16. doi: 10.3389/fimmu.2025.1529812. Full text in Research Archive
• Pivoriunas, Jonas; Engebretsen, Ingrid; Vethe, Nils Tore; Kristiansen, Oscar; Dammen, Toril & Husebye, Einar [Show all 9 contributors for this article] (2025). Statin adherence in coronary outpatients: The relationship between a novel blood test and pharmacy registry data. Atherosclerosis. ISSN 0021-9150. 403. doi: 10.1016/j.atherosclerosis.2025.119138. Full text in Research Archive
• Gosset, Clement; Barbosa, Susana; Destere, Alexandre; Cuozzo, Sebastien; Albano, Laetitia & Morelon, Emmanuel [Show all 25 contributors for this article] (2025). Maximum cold ischemia duration for a kidney allograft: a prediction model for allograft failure at the time of organ allocation. EClinicalMedicine. 85. doi: 10.1016/j.eclinm.2025.103322. Full text in Research Archive Show summary

  Background Many determinants of kidney allograft failure are established at the time of allocation by organ distribution agencies. At this point, the main modifiable factor is the duration of cold ischemia (CIT). Currently, no practical tool exists to determine the maximum permissible cold ischemia time for a specific recipient at allocation. Methods We analyzed two prospective cohorts of kidney transplant recipients from European centers: a derivation cohort of 7040 patients from 10 centers (Barcelona; Leuven; Oslo; Paris Necker, Lyon, Nantes, Nancy, Montpellier, Nice, Paris Saint Louis) with data collected between 2005 and 2020, and a validation cohort of 6131 patients from 6 French centers (Paris Necker, Lyon, Nantes, Nancy, Montpellier, Nice) with data collected between 2008 and 2019. The main outcome was allograft failure (return to dialysis or pre-emptive retransplantation). We assessed 26 determinants of allograft failure available at the time of allograft allocation including cold ischemia time as a modifiable factor. Prediction models were developed using a classical survival analysis and a competing risk framework. Findings Allograft failure occurred in 16% (1113) of the derivation cohort and 14% (832) of the validation cohort. Independent determinants of allograft failure were donor age (HR 2.2 [1.9–2.6] for donors above 65 years old), previous allografts (HR 1.5 [1.3–1.6]), dialysis history (HR 1.7 [1.3–2] for Hemodialysis), diabetes (HR 1.4 [1.2–1.6]), vascular disease (HR 1.3 [1.1–1.5]), HLA-DR incompatibility (HR 1.2 [1.1–1.3]), donor serum creatinine (HR 1 [1–1]), and cold ischemia time (HR 1 [1–1]). Donor age was the strongest contributor, while cold ischemia was the only modifiable factor. These factors were combined into two predictive models of kidney allograft failure (Cox regression and Fine Gray) showing accurate calibration, and discrimination with a C-Index of 0.66 (95% CI: 0.63–0.70 at year one) on the validation cohort for the Fine Gray model. The Fine–Gray model, which accounts for the competing risks between allograft failure and patient death, was used to develop a practical tool for predicting allograft failure based on cold ischemia. Interpretation Prediction model at the time of allocation provides a simple and practical tool which may guide organ distribution agencies and medico-surgical teams by customizing cold ischemia time for a kidney allograft transplantation. Funding Centaure Foundation (SIREN 499,947,398–http://www.fondation-centaure.org) none of the funding sources had any role in study.

• Arabaci, Öyküm Kaplan; Dančišinová, Zuzana & Paulsen, Ragnhild Elisabeth Heimtun (2025). The Chicken Embryo: An Alternative Animal Model in Development, Disease and Pharmacological Treatment. Pharmacology Research & Perspectives. 13(2). doi: 10.1002/prp2.70086. Full text in Research Archive
• Ortiz-Severín, Javiera; Tandberg, Julia Isabel; Winther-Larsen, Hanne Cecilie; Allende, Miguel L.; Cambiazo, Verónica & Chávez, Francisco P. (2025). In vivo host-pathogen dynamics and immune responses to Piscirickettsia salmonis using the zebrafish model. Microbial Pathogenesis. ISSN 0882-4010. 200. doi: 10.1016/j.micpath.2025.107349. Full text in Research Archive
• Glenna, Susanne; Birkeland, Einar Elvbakken; Orr, Russell; Gilfillan, Gregor; Dalland, Marianne & Økstad, Ole Andreas [Show all 8 contributors for this article] (2025). Skin bacterial community dynamics of hands and forearms before and after military field exercise. Microbiology spectrum. 13(5). doi: 10.1128/spectrum.02953-24. Full text in Research Archive Show summary

  The human skin microbiome is crucial for health and immunity, especially under the extreme conditions military personnel face. Soldiers often encounter unique stressors and hygienic challenges that can alter their skin’s microbial composition, particularly in field environments. In this study, we aimed to investigate the impact of military field exercises on the diversity and composition of the skin bacterial microbiota using 16S rRNA sequencing. We conducted a longitudinal study of Norwegian soldiers (n = 19) participating in outdoor training operations during the NATO winter exercise Cold Response 2022. Skin swabs were taken from soldiers' hands and forearms before and after the 10-day military exercise, and following a 3-week post-exercise leave. Our results reveal hand- and forearm-specific shifts in bacterial populations associated with the exercise, likely influenced by environmental exposure, reduced hygiene, and heightened social contact. Alpha diversity increased on forearms while remaining stable on hands, which appeared more resilient to perturbations. Both sites exhibited temporal changes in composition, with soil- and water-associated bacteria enriched post-exercise; most being transient on hands but more sustained on forearms. The soldiers’ microbiomes converged during the exercise, then diverged in the post-exercise leave period, and neither skin site returned to baseline composition at follow-up. Our findings highlight the impact of collaborative outdoor activities on microbial communities and suggest that resilience and stability differ between skin sites. IMPORTANCE Optimizing soldier health and resilience is critical for maintaining military readiness and operational effectiveness. The skin, as the body’s first line of defense, is subjected to numerous challenges in military environments. Unique environmental and hygiene challenges can disrupt the skin microbiome and increase susceptibility to skin and soft tissue infections. This longitudinal research provides valuable insights into the effects of military service on the bacterial dynamics of the skin microbiome but can also inform hygiene management and disease prevention in comparable situations.

• Ludvigsen, Lene Ugilt Pagter; Åsberg, Anders; Spetalen, Signe; Sørensen, Mia Dahl; Hamilton-Dutoit, Stephen & Gramkow, Ann-Maria [Show all 19 contributors for this article] (2025). Risk and prognosis of posttransplant lymphoproliferative disease in Epstein-Barr virus–seronegative kidney transplant recipients — an observational cohort study from Norway and western Denmark. American Journal of Transplantation. ISSN 1600-6135. 25(7), p. 1547–1560. doi: 10.1016/j.ajt.2025.01.035. Full text in Research Archive Show summary

  Posttransplant lymphoproliferative disorder (PTLD) poses a serious challenge in kidney transplant recipients. Epstein-Barr virus (EBV)-seronegative recipients have a significantly increased risk of PTLD, but few studies have investigated risk factors for PTLD in EBVseronegative recipients in the current era of immunosuppression. This cohort study from Norway and western Denmark included first-time kidney transplant recipients between 2007 and 2021 and estimated the cumulative incidence, risk, and prognosis of PTLD. In total, 80 of 5084 recipients developed biopsy-proven PTLD (median follow-up of 6.8 years). Two-year cumulative incidence of PTLD was 7.3% in EBV-seronegative adults and 14.1% in EBV-seronegative children. The age-adjusted hazard ratio (HR) for PTLD was 30.7 (95% CI, 13.9-67.9) in EBV-seronegative vs EBV-seropositive adults and 5.4 (95% CI, 1.1-26.9) in children. Recipients receiving induction therapy with antithymocyte globulin had an increased risk of PTLD (HR, 4.4; 95% CI, 1.8-10.6), while rituximab induction was associated with a lower risk of PTLD (HR, 0.20; 95% CI, 0.03-1.49). The age-adjusted mortality rate was higher in EBV-seronegative recipients with vs without PTLD (HR, 3.3; 95% CI, 1.3-8.3). In conclusion, the risk of PTLD in EBV-seronegative kidney transplant recipients is high in the contemporary era of immunosuppression. Induction therapy should be carefully considered in this high-risk population.

• Blandino, Alice; Scherer, Dominique; Boekstegers, Felix; Rounge, Trine B.; Langseth, Hilde & Roessler, Stephanie [Show all 11 contributors for this article] (2025). Small-RNA sequencing reveals potential serum biomarkers for gallbladder cancer: Results from a three-stage collaborative study of large European prospective cohorts. European Journal of Cancer. ISSN 0959-8049. 214, p. 1–10. doi: 10.1016/j.ejca.2024.115138. Full text in Research Archive Show summary

  Gallbladder cancer (GBC) is an aggressive disease with limited treatment options but high prevention potential. GBC tumours take 10–20 years to develop, a timeframe that holds potential for early detection. MicroRNAs (miRNAs) play a central role in abnormal cell processes, and circulating miRNAs may constitute valuable biomarkers of early disease. We used microarray data to pre-select differentially expressed miRNAs in formalin-fixed paraffin-embedded (FFPE) gallbladder tissue samples (GBC n = 40, normal n = 8). We then applied small-RNA sequencing to screen for miRNA expression differences in serum samples from three European prospective cohorts (n = 37 GBC case-control pairs), and validated the most promising candidates in three independent cohorts (n = 36 GBC case- control pairs). Statistical analyses included robust linear regression, pathway and meta-analysis, and examination of expression correlation between miRNAs and target genes. MiR-4533 and miR-671–5p were overexpressed in GBC tissue and serum samples, and meta-analysis confirmed the overexpression of miR-4533 in GBC serum samples from the prospective cohorts (p-value = 4.1×10-4), especially in individuals of female sex, under 63.5 years, or with a BMI below 26.2 kg/m2. Pathway and correlation analyses revealed that miR-4533 targets SIPA1L2 in the Rap1 signalling pathway, and SIPA1L2 was downregulated in GBC serum samples. Our study highlights the advantage of integrating small-RNA sequencing results from different types of samples and independent datasets, and the need for international research collaborations to identify and validate biomarkers for secondary prevention of rare tumours such as GBC. The function of miR-4533 and its interaction with SIPA1L2 in GBC development need to be further investigated.

• Carlsen, Rasmus Kirkeskov; Åsberg, Anders; Svensson, My Hanna Sofia; Birkeland, Kåre Inge; Jørgensen, Hanne Skou & Bressendorff, Iain [Show all 10 contributors for this article] (2025). Hypomagnesemia, insulin secretion and action in patients without diabetes, 1 year after kidney transplantation. Frontiers in Medicine. 12. doi: 10.3389/fmed.2025.1492871. Full text in Research Archive
• Syversen, Malin Olsen; Glatkauskas, Mikas; Mathiesen, Liv; Lea, Marianne; Denstad, Berit Gallefoss & Svensberg, Karin (2025). Facilitators and barriers to medication self-management for patients with multiple long-term conditions transitioning from hospital to home. Exploratory Research in Clinical and Social Pharmacy (ERCSP). 18. doi: 10.1016/j.rcsop.2025.100598. Full text in Research Archive
• Meer, Dennis van der; Hindley, Guy; Shadrin, Alexey; Smeland, Olav Bjerkehagen; Parker, Nadine & Dale, Anders M. [Show all 8 contributors for this article] (2025). Mapping the Genetic Landscape of Psychiatric Disorders With the MiXeR Toolset. Biological Psychiatry. ISSN 0006-3223. 98(6), p. 455–465. doi: 10.1016/j.biopsych.2025.02.886. Full text in Research Archive Show summary

  Psychiatric disorders have complex genetic architectures with substantial genetic overlap across conditions, which may partially explain their high levels of comorbidity. This presents significant challenges to research. Genome-wide association studies (GWASs) have uncovered hundreds of loci associated with single disorders, but the genetic landscape of psychiatric disorders has remained largely obscure. Moving beyond the conventional infinitesimal model, uni-, bi-, and trivariate MiXeR tools, applied to GWAS summary statistics, has enabled us to more comprehensively describe the genetic architecture of complex disorders and traits and their overlap. Furthermore, the GSA-MiXeR tool improves biological interpretation of GWAS findings to better elucidate causal mechanisms. Here, we outline the methodology that underlies the MiXeR tools together with instructions for their optimal use. We review results from studies that have investigated the genetic architecture of psychiatric disorders and their overlap using the MiXeR toolset. These studies have revealed generally high polygenicity and low discoverability among psychiatric disorders, particularly in contrast to somatic disorders. There is also pervasive genetic overlap across psychiatric disorders and behavioral traits, while their overlap with somatic traits is smaller, consistent with differences in polygenicity. Finally, GSA-MiXeR has quantified the contribution of gene sets to the heritability of psychiatric disorders, prioritizing small, biologically coherent gene sets. Together, these findings have implications for our understanding of the complex relationships between psychiatric disorders and related traits. MiXeR tools have provided new insights into the genetic architecture of psychiatric disorders, generating a better understanding of their underlying biological mechanisms and potential for clinical utility.

• Eide, Per Kristian; Hovd, Markus; Pripp, Are Hugo; Gjertsen, Øivind; Løvland, Grethe & Lashkarivand, Aslan [Show all 9 contributors for this article] (2025). Altered brain fluid dynamics in spontaneous intracranial hypotension. Fluids and Barriers of the CNS. 22. doi: 10.1186/s12987-025-00679-0. Full text in Research Archive Show summary

  Background This prospective observational study explored alterations in brain fluid dynamics in patients with spontaneous intracranial hypotension (SIH) and confirmed spinal cerebrospinal fluid (CSF) leakage, specifically addressing CSF clearance to blood, glymphatic influx and measures of CSF flow. Methods A cohort of SIH patients with verified spinal CSF leaks was compared with an age- and sex-matched reference group having no CSF disturbance or neurological disorders. Prior to repair of CSF leakage, CSF clearance was quantified using population pharmacokinetics, glymphatic influx was assessed by intrathecal contrast-enhanced magnetic resonance imaging (MRI), and CSF flow patterns were measured using either phase-contrast MRI or multiphase analysis of CSF tracer transport within the subarachnoid spaces. Results The study included eight SIH cases and nine reference subjects. SIH was accompanied with a greater CSF clearance, severely reduced tracer enrichment in the subarachnoid spaces and impaired glymphatic influx throughout the brain, after the patients had been upright. However, with patients in the supine position during MRI scanning, times to first enrichment of tracer in cisterna magna or perivascular subarachnoid spaces were not affected, with no changes in CSF flow through the Sylvian aqueduct, indicating that ventricular CSF production remained unaffected. Conclusions SIH caused by spinal CSF leakage is accompanied with altered brain fluid dynamics, here illustrated by accelerated CSF clearance to blood and reduced glymphatic influx, likely due to reduced CSF volume load to the intracranial compartment in the upright position.

• Stosic, Milan; Costanzi, Jean-Marc; Ambur, Ole Herman & Rounge, Trine Ballestad (2025). GENOMICON-Seq enables realistic simulation of amplicon and exome sequencing for low-frequency mutation detection. Scientific Reports. 15. doi: 10.1038/s41598-025-05267-8. Full text in Research Archive
• Burton, Joshua; Rounge, Trine Ballestad; Haugen, Trine B. & Wojewodzic, Marcin Wlodzimierz (2025). Networks of pre-diagnostic circulating RNA in testicular germ cell tumour. Scientific Reports. 15, p. 1–13. doi: 10.1038/s41598-024-84484-z. Full text in Research Archive Show summary

  Testicular germ cell tumour (TGCT) is a malignancy with known inherited risk factors, affecting young men. We have previously identified several hundred differentially abundant circulating RNAs in pre-diagnostic serum from TGCT cases compared to healthy controls. In this study, we performed Weighted Gene Co-expression Network Analysis (WGCNA) on mRNA and miRNA data from these samples. Central genes (hub genes) enriched functional pathways, and regulatory feature prediction were identified for all TGCT subtypes together and according to histology. The TGCT susceptibility genes TEX14, NARS2, and G3BP2, were identified as hub genes in both seminoma and non-seminoma networks. We also identified UBCA1, RCC1, FMR1, OAS3, and UBE2W as hub genes associated with TGCT. The genes OAS3 and UBE2W have previously been associated with testicular dysgenesis. Furthermore, network module analysis indicated transcription factors for oestrogen-related receptors to have a potential role during development of TGCT. The overlap between mRNA network hub genes and TGCT susceptibility genes indicates a common role in TGCT development.

• Boenink, Rianne; Bonthuis, Marjolein; Boerstra, Brittany A.; Astley, Megan E.; Sousa, Iris R. Montez de & Helve, Jaakko [Show all 45 contributors for this article] (2025). The ERA Registry Annual Report 2022: Epidemiology of Kidney Replacement Therapy in Europe, with a focus on sex comparisons. Clinical Kidney Journal (CKJ). ISSN 2048-8505. 18(2). doi: 10.1093/ckj/sfae405. Full text in Research Archive
• Skandalou, Eleni; Rivedal, Mariell Lossius; Marti, Hans Peter; Halden, Thea Anine Strøm; Jenssen, Trond & Vikse, Bjørn Egil [Show all 8 contributors for this article] (2025). Proteome of Renal Tubuli and Serum Differentiate Pre-Existing Type 2 Diabetes and Post-Transplant Diabetes in Kidney Transplant Recipients. PROTEOMICS - Clinical Applications. ISSN 1862-8346. 19(3). doi: 10.1002/prca.70000. Full text in Research Archive Show summary

  Purpose: Diabetes mellitus (DM) is a major cause of end-stage kidney disease (ESKD), with kidney transplantation being the preferred treatment. However, post-transplant diabetes mellitus (PTDM) increases mortality and graft loss. While PTDM and Type 2 diabetes mellitus (T2DM) share risk factors, their mechanisms differ, particularly in diabetic nephropathy (DN). This study aimed to investigate the molecular differences in PTDM by mapping the proteomes of proximal tubuli and serum in normoglycemic (NG), pre-transplant T2DM, and PTDM patients one year post-transplantation. Experimental Design Proteomic analysis was performed on microdissected proximal tubular cells and serum samples from kidney transplant recipients categorized as NG, pre-transplant T2DM, or PTDM at one year post-transplantation. Mass spectrometry was used to identify differentially expressed proteins. Data analyses were performed using gene ontology databases and pathway analysis. Results: Proteomic analysis revealed key differences, including significant dysregulation of mitochondrial proteins and lipid metabolism pathways in PTDM patients compared to T2DM and NG groups. Additionally, we observed distinct serum patterns of cholesterol metabolism dysregulation in PTDM, highlighting a complex interplay between fatty acid metabolism, mitochondrial dysfunction and systemic lipid dysregulation that may drive renal injury in PTDM-related DN. Conclusions and Clinical Relevance: This pilot study is the first to perform proteomic analysis on both microdissected tubular cells and serum from post-transplant PTDM, pre-transplant T2DM and NG transplant recipients. The proteomic differences between PTDM and T2DM could help to develop targeted therapies and early diagnostic markers, ultimately improving transplant outcomes and patient management. Further research is needed to validate these findings and explore their therapeutic potential.

• Drevland, Ole Martin; Muinck, Eric de; Trosvik, Pål; Hammerstad, Marta; Kvitne, Kine Eide & Midtvedt, Karsten [Show all 8 contributors for this article] (2025). Microbiome-derived reactivation of mycophenolate explains variations in enterohepatic recirculation in kidney transplant recipients. Microbiome. 13(1). doi: 10.1186/s40168-025-02142-6. Full text in Research Archive Show summary

  Background The pivotal role of microbes in drug metabolism is increasingly recognized, as variation in the gut microbiome composition between individuals has been shown to impact systemic drug exposure, efficacy and toxicity. Mycophenolate mofetil (MMF) is a cornerstone in immunosuppressive therapy following solid organ transplantation. However, dosing and tolerance are challenged by significant pharmacokinetic variability among patients, largely due to variable degrees of enterohepatic recirculation of mycophenolic acid (MPA), the active moiety of MMF. It is hypothesized that the variability in MPA recirculation is driven by gut microbiome-derived β-glucuronidase (β-GUS) mediated cleavage of MPA-glucuronide (MPAG) excreted in the bile. Here, we investigated the bidirectional interaction between MPA and the gut microbiome in kidney transplant recipients, using a combination of in vivo and in vitro data. Results We compared the fecal microbiomes of kidney transplant recipients (n = 21) both pre- and post-transplantation to healthy individuals (n = 15) using shotgun metagenomic sequencing. We also determined the individual microbiome-derived reactivation rate of MPAG to MPA and show a strong positive correlation between this reactivation rate and the degree of MPA enterohepatic recirculation in vivo. Through metagenomic analysis, the reactivation rate of MPA was linked to specific gut microbial species. In particular, specific β-GUS gene variants associated with Faecalibacterium prausnitzii showed a strong impact on the conversion of MPAG to MPA. Furthermore, our study confirmed a significant shift in microbial composition post-transplantation and revealed notable fluctuations in species such as F. prausnitzii and Akkermansia muciniphila across different time points after transplantation. Lastly, we provide evidence that the microbiome-derived reactivation rate of MPA is linked to specific beta-glucuronidase alleles. Conclusions We highlight for the first time that the ex vivo determined reactivation rate of MPA explains the variation of enterohepatic recirculation, emphasizing the important role of F. prausnitzii in this process. More broadly, our findings suggest that the gut microbiome significantly influences the degree of enterohepatic recirculation of MPA, providing valuable insights that could be relevant for optimizing individualized immunosuppressive drug dosing in transplant patients.

• Pivoriunas, Jonas; Vethe, Nils Tore; Kristiansen, Oscar; Bergan, Stein; Husebye, Einar & Munkhaugen, John [Show all 7 contributors for this article] (2025). Low-Density Lipoprotein Cholesterol Increases Significantly During Brief Discontinuation of Atorvastatin and Correlates With Metabolite Half-Lives. Pharmacology Research & Perspectives. 13(2). doi: 10.1002/prp2.70082. Full text in Research Archive Show summary

  Variability in low-densitylipoprotein cholesterol (LDL-C) has emerged as a potential independent cardiovascular risk factor, but the impact of short-term discontinuation of statins on LDL-C remains to be defined. Furthermore, the relationship between individual statin metabolites and changes in LDL-C has not yet been examined. The present study aimed to investigate changes in LDL-C concentrations during a four-day discontinuation of atorvastatin therapy and to examine correlations between the half-lives of atorvastatin metabolites and LDL-C concentrations. This pharmacokinetic intervention study included 60 adults with confirmed adherence to atorvastatin, using doses of 20 mg (N = 20), 40 mg (N = 20), or 80 mg (N = 20) at study start. Atorvastatin was then discontinued, and blood samples were collected from day zero to day four. We assessed daily concentrations of LDL-C and of atorvastatin with its metabolites by liquid chromatography–tandem mass spectrometry. The mean (SD) LDL-C at baseline was 1.84 (0.6) mmol/L. LDL-C increased on average by 0.50 mmol/L (27%) from day zero to day four. The increase in LDL-C was significant already 48 h after the last statin intake and was affected by individual variation in baseline concentrations and the slope of the daily increase. A moderate correlation was found between differences in LDL-C concentrations and the half-lives of hydroxylated atorvastatin metabolites. In conclusion, 4 days without atorvastatin resulted in an almost 30% increase in LDL-C concentrations, and the increase was significant already after the first omitted dose. The half-lives of hydroxylated atorvastatin metabolites showed a moderate correlation with the increase in LDL-C concentrations.

• Zakhartseva, Ekaterina Avershina; Qureshi, Arfa Irej; Winther-Larsen, Hanne Cecilie & Rounge, Trine Ballestad (2025). Challenges in capturing the mycobiome from shotgun metagenome data: lack of software and databases. Microbiome. 13(1). doi: 10.1186/s40168-025-02048-3. Full text in Research Archive Show summary

  Background The mycobiome, representing the fungal component of microbial communities, is increasingly acknowledged as an integral part of the gut microbiome. However, research in this area remains relatively limited. The characterization of mycobiome taxa from metagenomic data is heavily reliant on the quality of the software and databases. In this study, we evaluated the feasibility of mycobiome profiling using existing bioinformatics tools on simulated fungal metagenomic data. Results We identified seven tools claiming to perform taxonomic assignment of fungal shotgun metagenomic sequences. One of these was outdated and required substantial modifications of the code to be functional and was thus excluded. To evaluate the accuracy of identification and relative abundance of the remaining tools (Kraken2, MetaPhlAn4, EukDetect, FunOMIC, MiCoP, and HumanMycobiomeScan), we constructed 18 mock communities of varying species richness and abundance levels. The mock communities comprised up to 165 fungal species belonging to the phyla Ascomycota and Basidiomycota, commonly found in gut microbiomes. Of the tools, FunOMIC and HumanMycobiomeScan needed source code modifications to run. Notably, only one species, Candida orthopsilosis, was consistently identified by all tools across all communities where it was included. Increasing community richness improved precision of Kraken2 and the relative abundance accuracy of all tools on species, genus, and family levels. MetaPhlAn4 accurately identified all genera present in the communities and FunOMIC identified most species. The top three tools for overall accuracy in both identification and relative abundance estimation were EukDetect, MiCoP, and FunOMIC, respectively. Adding 90% and 99% bacterial background did not significantly impact these tools’ performance. Among the whole genome reference tools (Kraken2, HMS, and MiCoP), MiCoP exhibited the highest accuracy when the same reference database was used. Conclusion Our survey of mycobiome-specific software revealed a very limited selection of such tools and their poor robustness due to error-prone software, along with a significant lack of comprehensive databases enabling characterization of the mycobiome. None of the implemented tools fully agreed on the mock community profiles. FunOMIC recognized most of the species, but EukDetect and MiCoP provided predictions that were closest to the correct compositions. The bacterial background did not impact these tools’ performance. Video Abstract

• Skagen, Christine; Stevanovic, Stanislava; Bakke, Hege Gilbø; Nyman, Tuula Anneli; Stensland, Maria & Kase, Eili Tranheim [Show all 9 contributors for this article] (2025). Reduced lipid and glucose oxidation and reduced lipid synthesis in AMPKα2/ myotubes. Archives of Physiology and Biochemistry. ISSN 1381-3455. 131(3), p. 483–492. doi: 10.1080/13813455.2024.2449409. Full text in Research Archive Show summary

  Adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK) plays a crucial role in regulation ofmetabolic homeostasis. To understand the role of the catalytic α2 subunit of AMPK in skeletal muscleenergy metabolism, myotube cultures were established from AMPKα2+/+ and AMPKα2-/- mice. Myotubesfrom AMPKα2-/- mice had lower basal oleic acid and glucose oxidation compared to myotubes fromAMPKα2+/+ mice. However, the relative response to mitochondrial uncoupling was increased for oleicacid oxidation. Incorporation of acetate into lipids was also lower in myotubes from AMPKα2-/- mice.Proteomics analysis revealed that AMPKα2-/- myotubes had upregulated pathways related to mitochondrialfunction and fatty acid oxidation, and decreased pathways related to fatty acid biosynthesis. Inconclusion, ablation of AMPKα2 catalytic subunit in skeletal muscle cells resulted in reduced basaloxidation of glucose and fatty acids, however upregulated pathways related to mitochondrial functionand fatty acid oxidation and reduced lipid formation

• Hole, Kristine & Molden, Espen (2025). Association Between CYP2D6 Genotypes and Serum Concentrations of Mirtazapine and Mianserin. Basic & Clinical Pharmacology & Toxicology. ISSN 1742-7835. 136(4). doi: 10.1111/bcpt.70013. Full text in Research Archive Show summary

  The aim of the present study was to investigate the effect of CYP2D6 genotypes on mirtazapine and mianserin serum concentrations. Patients were included retrospectively from a therapeutic drug monitoring service. Multiple linear regression analysis was used to investigate the effect of CYP2D6 genotype, age and sex on mirtazapine and mianserin concentration-to-dose (C/D) ratio. The study included 2315 mirtazapine patients and 474 mianserin patients who were assigned to the genotype-predicted phenotype groups of CYP2D6 poor metabolizers (PMs), intermediate metabolizers (IMs), normal metabolizers (NMs) and ultrarapid metabolizers (UMs). Multiple linear regression analysis revealed 18% and 14% higher mirtazapine C/D ratio in CYP2D6 PMs and IMs, respectively, compared with NMs (p ≤ 0.004). For mianserin, the C/D ratio was 80% and 45% higher in PMs and IMs, respectively, compared with NMs (p < 0.001). The C/D ratio in UMs did not differ from NMs for either drug (p ≥ 0.3). In conclusion, CYP2D6 genotype was only associated with a minor change in mirtazapine serum concentration. The association between CYP2D6 genotype and mianserin serum concentration was greater, with 80% higher mianserin C/D ratio in CYP2D6 PMs compared with NMs.

• Glatkauskas, Mikas; Syversen, Malin Olsen; Lea, Marianne; Scott, Michael; Svensberg, Karin & Denstad, Berit G. [Show all 8 contributors for this article] (2025). Application of a human factors approach to investigate the hospital to home transition for patients with multiple long-term conditions. Human Factors in Healthcare (HFH). 7. doi: 10.1016/j.hfh.2025.100100. Full text in Research Archive
• Solbakk, Maria; Smith, Robert Løvsletten; Wollmann, Birgit Malene Tovik; Bråten, Line Skute; Johansson, Inger & Ingelman-Sundberg, Magnus [Show all 8 contributors for this article] (2025). Impact of the transcription factor nuclear factor 1 B T>C polymorphism on clozapine metabolism in vivo and expression of intestinal transporters in vitro. Drug Metabolism And Disposition. ISSN 0090-9556. 53(7). doi: 10.1016/j.dmd.2025.100100. Full text in Research Archive
• Tingstad, Ragna Husby; Witczak, Oliwia; Beajani, Siver; Seo, Seaung Hee; Løvsletten, Nils Gunnar & Skagen, Christine [Show all 11 contributors for this article] (2025). Impact of Short-Chain Fatty Acids on Glucose, Fatty Acid and Leucine Metabolism in Primary Human Myotubes. Endocrinology, Diabetes & Metabolism. 8(2). doi: 10.1002/edm2.70042. Full text in Research Archive Show summary

  Introduction Short-chain fatty acids (SCFAs) are small molecule metabolites mainly produced during microbial fermentation of dietary fibre in the gut and have been shown to have a beneficial impact on human health. The aim of this study was to evaluate the effect of SCFAs on human skeletal muscle energy metabolism. Methods Primary human myotubes were analysed for glucose and fatty acid (oleic acid) metabolism, as well as insulin sensitivity and protein synthesis in the presence or absence of SCFAs. Results The most pronounced effects of SCFAs were observed on 14C-oleic acid uptake and oxidation, as well as 14C-leucine uptake and protein synthesis, following butyrate treatment. Butyrate increased 14C-leucine accumulation twofold, potentially due to protein incorporation. On the other hand, the conversion of 14C-leucine into free fatty acids was reduced by more than 50% by butyrate. Both 14C-acetate and 14C-butyrate were shown to be taken up and utilised by primary human myotubes. None of the SCFAs were found to influence glucose metabolism or insulin effects. Conclusion The results from the current study thus suggest that among the SCFAs, butyrate emerges as the most powerful SCFA in regulating primary human myotube metabolism.

• Syversen, Malin Olsen; Glatkauskas, Mikas; Sedeniussen, Sandra Johanne; Hauge, Monica; Benny, Steffi & Horgen, Kristine [Show all 12 contributors for this article] (2025). Discrepancies in medication lists after hospital discharge in patients with multiple long-term conditions. Research in Social and Administrative Pharmacy. ISSN 1551-7411. 21(8), p. 580–588. doi: 10.1016/j.sapharm.2025.03.062. Full text in Research Archive Show summary

  Background Inadequate information flow in the transition from hospital to home poses a challenge to medication safety, especially for patients with multiple long-term conditions (MLTCs). Purpose To investigate the frequency, categories, underlying reasons, and potential clinical relevance of medication discrepancies (MDs) by comparing medication lists in hospital discharge summaries with actual medication use after discharge in patients with MLTCs. Methods Home-dwelling adult patients with MLTCs, using minimum four medications were included near the time of their planned discharge, from one internal medicine and two geriatric wards in Oslo, to this cross-sectional observational study. Medication reconciliation was performed 1–2 weeks post-discharge. Discrepancies between the medication list in the discharge summary and the patient's medication use were classified into six categories. A panel assessed the potential clinical relevance of the MDs in a short-term and long-term perspective. Results 150 patients, median age 75 years (range 22–94), were included. 132 (88 %) had at least one MD, with a median of 3 per patient (range 0–10). The most common MDs involved medications in use although not listed in the discharge summary. Apparent lack of or insufficient medication reconciliation during the hospital stay was the most frequent reason for MDs. Of the MDs, 5.5 % and 28 % were assessed to be of potential clinical relevance in the short-term and long-term perspective, respectively. Conclusion Almost all patients had MDs following hospital discharge. The potential clinical relevance increases over time if MDs are not corrected. Our findings highlight the need for more effective interventions to ensure medication safety in care transitions for this vulnerable population.

• Lambertus, Marvin; Geiseler, Samuel Jakob & Morland, Cecilie (2024). High-intensity interval exercise is more efficient than medium intensity exercise at inducing neurogenesis. Journal of Physiology. ISSN 0022-3751. 602(24), p. 7027–7042. doi: 10.1113/JP287328. Full text in Research Archive

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• Kongerud, Ingrid Charlotte; Midtvedt, Karsten; Solbu, Marit Dahl; Øvrehus, Marius Altern; Eikrem, Øystein Solberg & Eide, Ivar Anders [Show all 10 contributors for this article] (2026). Can sodium-glucose cotransporter 2 (SGLT2) inhibition preserve renal structure and function in de novo kidney transplant recipients? Protocol for a randomised, double-blind, placebo-controlled trial assessing the efficacy of dapagliflozin on kidney structure, function and safety in kidney transplant recipients in Norway—the DEAK study. doi: 10.1136/bmjopen-2026-117263. Full text in Research Archive Show summary

  Introduction Recent studies have shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors slow the progression of chronic kidney disease in people at high cardiovascular risk, with or without type 2 diabetes. To date, all published studies have excluded kidney transplant recipients (KTRs). The Dapagliflozin Early After Kidney Transplantation (DEAK) study aims to prospectively evaluate the effects of the SGLT2 inhibitor dapagliflozin on kidney function, histopathology and metabolic outcomes among de novo KTRs. Methods and analyses This nationwide, investigator-initiated, single-transplant-centre, randomised, placebo-controlled, prospective clinical trial with two parallel groups aims to enrol 330 de novo adult KTRs (aged 18–75 years) with an estimated glomerular filtration rate (eGFR) of at least 25 mL/min/1.73 m². Participants are enrolled 6–8 weeks after transplantation and randomised 1:1 to receive dapagliflozin 10 mg/day or placebo for 3 years. Recipients with conditions that may intermittently affect kidney function, such as recent acute rejection or ongoing infection, are ineligible for inclusion. The primary endpoint of the study is the difference in the chronic eGFR slope between treatment groups over 3 years, estimated using the European Kidney Function Consortium equation. Secondary and safety endpoints include changes in measured GFR (iohexol clearance), urinary albumin/creatinine ratio, blood pressure, infections and safety clinical chemistry. Exploratory endpoints evaluated after 1.5 years include changes in body composition and glucose tolerance; between-group differences in urinary metabolomics; transplant kidney biopsy inflammation and fibrosis scores (n=140) and kidney biopsy messenger RNA and protein expression (n=50). The protocol also includes a 10-year poststudy registry follow-up of eGFR slope, cardiovascular events and graft and patient survival. Ethics and dissemination The study protocol (EudraCT number: 2022-002428-10) has been approved by the Norwegian Medical Products Agency, the Regional Committee for Medical Research Ethics in Southeast Norway (REK Southeast number 426076) and by the data protection offices at the participating hospitals. The main results will be published in international, peer-reviewed scientific journals. Trial registration number NCT05788276.

• Dietrichs, Erik Sveberg; Rogne, Tormod; Solberg, Carl Tollef & Nordengen, Kaja (2026). Norge trenger flere forskere, da må vi rekruttere tidligere. Full text in Research Archive Show summary

  KRONIKK: For første gang på 55 år er det nedgang i antall forskere. Ved norske universiteter og høyskoler var det 770 færre forskere i 2024 sammenlignet med 2023.

• Rounge, Trine Ballestad & Paulsen, Jonas (2025). Highly sensitive method captures rare RNAs in blood to search for disease. Nature. ISSN 0028-0836. 641(8063), p. 599–600. doi: 10.1038/d41586-025-01127-7. Full text in Research Archive
• Åsberg, Anders; Midtvedt, Karsten; Lindahl, Jørn Petter Hanto; Pihlstrøm, Hege K.; Bollerslev, Jens & Godang, Kristin (2025). Impact of Potassium-Binders on the Interpretation of Bone Mineral Density Following Kidney Transplantation. Clinical Transplantation. ISSN 0902-0063. 39(10). doi: 10.1111/ctr.70352. Full text in Research Archive
• Klevmoen, Marianne; Mulder, Janneke W.C.M.; Bogsrud, Martin Prøven; Retterstøl, Kjetil; Vesterbekkmo, Elisabeth Kleivhaug & Pedersen, Eva Ringdal [Show all 16 contributors for this article] (2025). Prospective study on breastfeeding, lipid profile and cardiovascular risk markers in women with familial hypercholesterolaemia: study protocol for the FH-FEMINA study. doi: 10.1136/bmjopen-2024-092208. Full text in Research Archive
• Scherer, Dominique; Ponce, Carol Barahona; Mengoa, Claudio; Montenegro, Paola; Losada, Hector & Garcia, Ana Lineth [Show all 31 contributors for this article] (2025). Data Resource Profile: EULAT Eradicate GBC: the European-Latin American Research Consortium towards Eradication of Preventable Gallbladder Cancer. International Journal of Epidemiology. ISSN 0300-5771. 54(4). doi: 10.1093/ije/dyaf127. Full text in Research Archive
• Fløde, Mari; Hermann, Monica; Igland, Jannicke; Hernar, Ingvild; Sigurdardottir, Arun Kristin & Søfteland, Eirik [Show all 9 contributors for this article] (2025). Hypoglykemi hos eldre med diabetes - samanhengar med diabetes- og aldersrelaterte faktorar. Full text in Research Archive
• Lea, Marianne (2025). Legen kuttet medisiner for eldre: – Noen kunne dra på hytta igjen, gå på svaberg og gå turer. [Journal]. Fagbladet. Full text in Research Archive Show summary

  – Legemidler også omsorg Det trenger ikke være en motsetning mellom omsorg og legemidler, mener postdoktor Marianne Lea.

• Lea, Marianne (2025). (+) – Å fjerne en diagnose kan i mange tilfeller være helsefremmende. [Journal]. Psykologisk.no. Full text in Research Archive Show summary

  Stadig flere får en psykiatrisk diagnose. Postdoktor Marianne Lea mener det er på tide å snakke om det motsatte av diagnostisering – nemlig avdiagnostisering.

• Lea, Marianne & Mathiesen, Liv (2025). Økt pasientsikkerhet gjennom bedre informasjonsflyt om legemidler. Full text in Research Archive Show summary

  Vi ønsker å øke pasientsikkerheten gjennom å bedre informasjonsflyten om legemidler når pasienter overflyttes mellom helsetjenestenivåer. Det siste tiåret har vi gjennomført flere forskningsprosjekter som omhandler overganger i helsevesenet og optimalisering av legemiddelbehandling.

• Frøiland, Hilde & Lea, Marianne (2025). Bokanmeldelse: Snevert og ensidig om avmedisinering - Farmatid. Norsk Farmaceutisk Tidsskrift (NFT). ISSN 0029-1935. Full text in Research Archive Show summary

  Boken Mindre medisiner – mer omsorg. En håndbok i avmedisinering av eldre av sykehjemsoverlege Pernille Bruusgaard, tar opp et viktig og aktuelt tema: Avmedisinering og omsorg for eldre sykehjemspasienter. I boken utfordrer forfatteren etablerte praksiser og stimulerer til refleksjon rundt legemiddelbehandling, særlig på sykehjem. Det er et modig prosjekt – og et prosjekt som fortjener oppmerksomhet. Samtidig er det flere sider ved boken som gjør at den bør leses med et kritisk blikk og helst etterfulgt av diskusjon og samtale med andre fagpersoner.

• Glatkauskas, Mikas; Lea, Marianne & Mathiesen, Liv (2025). How to meet the patients needs? Employing design thinking into pharmaceutical care innovation projects. Full text in Research Archive
• Rimstad, Espen; Brinchmann, Jan Engelsen; Frostegård, Åsa; Sipinen, Ville Erling; Tønnessen, Ragnhild & Blix, Hege Salvesen [Show all 9 contributors for this article] (2025). Environmental risk assessment of the genetically modified vaccine Recombitek®C4. VKM Bulletin. VKM Bulletin(VKM Bulletin 2025: 02), p. 1–22. Full text in Research Archive Show summary

  Det er ikke høyere miljørisiko ved bruk av den genmodifiserte vaksinen Recombitek®C4 enn ved bruk av tilsvarende godkjente vaksiner. Det er hovedbudskapet i en risikovurdering VKM har gjort for Miljødirektoratet. Bakgrunn Miljødirektoratet har mottatt en søknad etter genteknologiloven om bruk av vaksinen Recombitek®C4 i det nasjonale avlsprogrammet for fjellrev (Vulpes lagopus). Fjellreven er klassifisert som en sterkt truet art i Norge. Avlsprogrammet er etablert som del av bevaringsarbeidet og driftes av Norsk institutt for naturforskning (NINA). Ved avlsstasjonen i Oppdal har fire revevalper dødd av smittsom leverbetennelse (hepatitis contagiosa canis (HCC)), og man ønsker å bruke denne vaksinen for å hindre ytterligere smitte. Det finnes godkjente alternative vaksiner til Recombitek®C4, men disse ønsker man ikke å bruke fordi vaksinene inneholder et svekket (for hund), men levende valpesykevirus (CDV), som kan føre til sykdom hos fjellrev. Recombitek®C4 er pr i dag ikke godkjent i Norge eller i EU, men er blitt regelmessig brukt til vaksinasjon av hunder i over 20 år, blant annet i USA og Canada. Miljødirektoratet har bedt VKM utføre en miljørisikovurdering av vaksinen Recombitek®C4 i henhold til genteknologiloven VKMs vurdering Vaksinen Recombitek®C4 inneholder en kanarikoppevirusvektor kalt ALVAC. ALVAC er basert på Kanarikoppeviruset (CNPV), som først og fremst forårsaker sykdom hos spurvefugler, som kanarifugl. Forløpet kjennetegnes ved sykdom i hud og difteriliknende symptomer, med mulig høy dødelighet. ALVAC er en genetisk konstruert, svekket variant av CNPV, designet for bruk i vaksiner. Hverken vektoren eller viruset kan produsere eller spre nye virus mellom pattedyr. Dermed vil den mest sannsynlige veien til miljøet være via overføring til ville fugler. Avlsstasjonen i Oppdal rapporterer om en viss interaksjon mellom fjellrev og fugler, som ørn, ravn og kråke, bl.a. rundt fôrplasseringer. For å minimere mulig kontakt mellom rev og fugl, bruker man fôringsbokser og spesielle «ørnestrukturer» i innhegningene. Dersom ørn eller andre fugler likevel skulle komme i kontakt med ALVAC i perioden revene vaksineres, anses faren for smitte, sykdom og spredning blant fugler som svært usannsynlig. Flere vaksiner som inneholder ALVAC er godkjente til bruk på dyr i Norge, for eksempel i vaksiner til katt og hest. VKM konkluderer at bruk av Recombitek®C4 i det nasjonale avlsprogrammet for den rødlistede arten fjellrev ikke utgjør en økt miljørisiko sammenlignet med tilsvarende vaksiner med ALVAC-vektoren allerede i bruk for andre dyrearter i Norge. Risikovurderingen er godkjent av VKMs faggruppe for genmodifiserte organismer - legemidler.

• Mathiesen, Liv; Wøien, Hilde & Reinås, Karl Henrik Storhaug (2025). Fasilitatorutdanning - et pedagogisk tilbud for å styrke studentenes læringsutbytte for tverrprofesjonell samarbeidslæring i praksis. Full text in Research Archive Show summary

  Innledning: SamPraks, UiOs modell for tverrprofesjonell samarbeidslæring (TPS), oppskaleres kraftig for å møte RETHOS’ føringer. For å sikre kvaliteten på studentenes læringsutbytte må flere kompetente fasilitatorer utdannes. Studentene har i flere år verdsatt fasilitering av praksisen i sine evalueringer. Faglærerne har på sin side etterstrebet å øke egen fasilitatorkompetanse og etablere et pedagogisk grunnlag for fasilitering av SamPraks. Betydningen av en solid og konsistent pedagogikk for TPS er forankret gjennom mange år i en rekke forskningsstudier. I 2023 bestemte vi oss derfor for å etablere et pedagogisk tilbud for å gi nye og eksisterende fasilitatorer i SamPraks en omfattende opplæring til denne funksjonen. Metode: Gjennom samarbeid med pedagoger ved Det utdanningsvitenskapelige fakultet ved UiO utviklet vi et fasilitatorkurs for vitenskapelige ansatte, som gir en uttelling på 15 timers universitetspedagogisk basiskompetanse. Som forberedelse før kursstart må deltakerne gjennomføre SamPraks’ digitale introduksjonskurs, og skrive et refleksjonsnotat. Deretter kommer to samlinger med teori om gruppedynamikk og TPS. Avslutningsvis får deltakerne praktisk opplæring i å fasilitere tverrprofesjonelle grupper; først som observatører av en erfaren fasilitator, og dernest som aktive fasiliatatorer med en erfaren pedagog som støtte. Det er utviklet en manual som bidrar til å gi retning og veiledning i hvordan man kan skape god fasilitering og gi studentene et godt læringsutbytte. Resultater: Vi har nå gjennomført to fasilitatorkurs og utdannet tilsammen 17 nye SamPraksfasilitatorer. Etter gjennomført fasilitatorkurs er deltagerne selvstendige, og de utgjør allerede en avgjørende ressurs for gjennomføringen av SamPraks og kvaliteten på den TPS-en. Oppsummering: Fasilitatorene er avgjørende i å sikre kvaliteten på læringsutbyttet for studentene i TPS. Gjennom aktiv støtte til å fremme læringsprosesser bidrar fasilitatorene til at studentene i større grad kan utnytte læringspotensialet som ligger i å lære av, med og om hverandre i praksis. 'Stiftelsen til fremme for norsk apotekfarmasi' har bidratt til finansiering av kursene.

• Lislerud, Anna; Saragliadis, Athanasios; Nakatani, Hajime; Hori, Katsutoshi & Linke, Dirk (2025). Investigating the role of the YrInv and YrIlm inverse autotransporter invasins in Y. ruckeri pathogenesis. Full text in Research Archive
• Naqvi, Maria (2025). The State of the Ocular Microbiome in Dry Eye Disease: Patterns, Problems and Possibilities. OsloMet - storbyuniversitetet. ISSN 9788283646498. Full text in Research Archive Show summary

  The composition of the ocular microbiome, and the involvement of these microbes in ocular surface health and disease is an area of active research. Tear film hyperosmolarity initiates a cascade of events including inflammatory responses in dry eye disease (DED). We hypothesized that the structure of and disturbances in the ocular microbiome may be important in the progress and symptoms of the disorder and aimed to characterize the ocular microbiome in dry eye patients and controls to see if leads concerning its potential involvement in the condition emerged. We recruited participants with clinically confirmed DED and healthy individuals and analysed, compared and contrasted their ocular microbiomes. Characterization was performed using both culture-dependent and culture-independent methods. Both methods indicated that the ocular surface was mostly colonized by CoNS, Corynebacterium and Cutibacterium regardless of ocular health state. The opportunistic pathogens S. aureus and E. faecalis were also isolated from the ocular surface. Species belonging to the Corynebacterium genus were characterized using WGS and phenotypic tests to examine their pathogenicity potential on the ocular surface. Their interaction with one another and other ocular bacteria was also investigated. Furthermore, all isolates identified as S. aureus and as E. faecalis were investigated using WGS, in silico approaches to reveal pathogenicity and antibiotic susceptibility tests owing to their known associations with ocular infections. Lastly, various supervised machine learning approaches were used to identify potential biomarkers of DED. The work performed in this thesis supports previous finding regarding the ocular surface microbiome. It also extends the reach of previous work and suggests several new avenues of research, particularly with regard to ocular Corynebacterium. The majority of the Corynebacterium species were found to have lipase and mucinase activity on agar, which could be clinically important. Pertinently, some isolates were also found to inhibit other bacteria present on the ocular surface, which could have an impact on the ocular surface microbiome and its stability – and by extension its protective functions. The interactions of Corynebacterium with immune cells and epithelial cell should be further investigated. Although S. aureus and E. faecalis were isolated from patients without ocular infections, the species did show virulence and pathogenicity potential. The supervised ML models were able to distinguish between dry and healthy eyes based on the bacterial community and demonstrated an alternative hypothesis generating approach which can be used in future studies.

• Lauritzen, Trine & Vethe, Nils Tore (2025). New pathophysiological knowledge and diagnostic biomarkers for atorvastatin-dependent muscle side effects in patients with coronary heart disease. Universitetet i Oslo. ISSN 9788234806605. Full text in Research Archive Show summary

  Statins are central to secondary prevention of coronary heart disease, yet statin-associated muscle symptoms (SAMS) often result in discontinuation of treatment. SAMS often have non-statin causes, and no validated objective test distinguishes them from true intolerance. This thesis lies at the intersection of cardiovascular disease prevention and clinical pharmacology and sought to clarify mechanisms behind SAMS and to assess whether a simple blood test can separate atorvastatin intolerance from symptoms of other origin. The results are based on a randomised, double-blind crossover trial in patients with SAMS (MUSE RCT) and a sub-study with paired plasma and muscle biopsies (MUSE BmS). The patients were clinically categorised as statin-tolerant or intolerant. Using LC-MS/MS, we measured mevalonate and atorvastatin acid with its metabolites in plasma and muscle. We also genotyped variants affecting statin metabolism and distribution and examined muscle histology. Plasma- and muscle concentrations were strongly correlated, indicating plasma can proxy muscle exposure. Compared with tolerant patients, statin-intolerant patients had lower levels of active (acid) metabolites and higher lactone/acid ratios, consistent with a shift toward myotoxic metabolites. Some of the genetic variants were associated with higher lactone levels. Mevalonate and LDL-cholesterol fell with statin treatment, but less in the intolerant group, mirroring lower atorvastatin acid exposure. Biopsies were not decisive; occasional necrotic fibres on-statin did not match clinical intolerance. In sum, a blood-based signature—low acid metabolites, elevated lactone/acid ratio, and a lesser fall in mevalonate and LDL-C—might be a tool to rule out many statin-tolerant patients and focus evaluation and follow-up on the intolerant. Validation in larger cohorts is needed; if confirmed, this approach could enable more personalised therapy, reduce unnecessary discontinuation, and improve cardiovascular outcomes.

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