Communications medicine最新文献

{"title":"Progress, challenges, and future directions of pancreatic cancer surveillance in high-risk populations.","authors":"Ashleigh R Poh, Adrienne Sexton, Halina Pietrzak, Rebekah De Losa, Raffiela Garcia, Natalie Heriot, Ingrid Winship, Andrew J Metz","doi":"10.1038/s43856-026-01822-0","DOIUrl":"10.1038/s43856-026-01822-0","url":null,"abstract":"<p><p>Pancreatic cancer remains one of the most lethal malignancies because most patients are diagnosed with advanced disease, when curative treatment is rarely possible. Population-wide screening is not currently recommended because pancreatic cancer remains relatively uncommon. Early detection efforts therefore focus on surveillance of individuals at substantially elevated risk, including those with hereditary cancer syndromes, pathogenic germline variants, or a strong family history of pancreatic cancer. Surveillance is primarily performed using magnetic resonance imaging and endoscopic ultrasound to detect early-stage cancer or high-risk precursor lesions. In this Review, we summarise current evidence for pancreatic cancer surveillance in high-risk populations. We discuss approaches to risk identification, surveillance eligibility, imaging strategies, and reported clinical outcomes. We also examine important challenges, including interval cancers, risk stratification, psychological impact, cost-effectiveness, and implementation in clinical practice. Finally, we review emerging approaches, including biomarkers and risk prediction models, that may further improve early detection.</p>","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":"6 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13444134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148680715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic fragility in European total intravenous anesthesia delivery and opportunities for resilient real-time decision support.","authors":"Clara Ionescu, Erhan Yumuk, Michele Schiavo, Antonio Visioli, Massimiliano Paltenghi, Nicola Latronico, Bob Aubouin Pairault, Mirko Fiacchini, Kaouther Moussa, Cristina Muresan, Isabela Birs, Eva Dulf, Teodora Mocan, Lucian Mocan, Robert Szabo, Dana Copot","doi":"10.1038/s43856-026-01833-x","DOIUrl":"10.1038/s43856-026-01833-x","url":null,"abstract":"<p><p>Total intravenous anesthesia (TIVA) is a well-established technique for general anesthesia and is increasingly relevant to Europe's transition toward more digital, sustainable, and patient-centred healthcare. However, its use remains uneven across centres and still depends heavily on population-based drug models, variable monitoring practices, and repeated clinician adjustment. Differences in training, data access, device compatibility, patient response, and institutional resources can limit safe and consistent personalization. In this Review, we examine the main sources of fragility in current TIVA practice and discuss how interoperable perioperative data, digital patient simulators, patient-adaptive models, multimodal monitoring, and closed-loop decision support could improve safety and resilience. We emphasize that these technologies should support, not replace, the anesthesiologist, and should remain transparent, clinically supervised, and easy to override. We conclude by outlining priorities for European collaboration in data infrastructure, training, validation, regulation, and evaluation of AI-enabled tools.</p>","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":"6 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13428739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148655109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Asymmetric plantar temperature downshifts are associated with atrial fibrillation and thromboembolic events: an observational post hoc analysis of the SmartPreventDiabeticFeet study.","authors":"Antao Ming, Fidan Asadzade, Yunxin Zhang, Jaqueline Hötzsch, Gorre Sudha, Peter R Mertens","doi":"10.1038/s43856-026-01811-3","DOIUrl":"10.1038/s43856-026-01811-3","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular and thromboembolic complications remain a major burden in diabetes. We aimed to determine whether peripheral thermometry is suited to detect plantar temperature downshifts (PTDs). Plantar infrared images (PIRIs) and sensor recordings were correlated with atrial fibrillation (AF) and thromboembolic events in patients with diabetes.</p><p><strong>Methods: </strong>A secondary analysis of the SmartPreventDiabeticFeet study including 239 patients monitored by PIRIs and sensor-equipped insoles (median follow-up 67.1 months) was conducted. In a structured telephone survey, histories of AF and thromboembolic events (stroke, pulmonary embolism [PE], peripheral arterial disease [PAD]) were captured from enrollment to post-intervention period. Patients with >30 days of temperature recordings (n = 118) were classified according to pre-specified PTD definitions, unsupervised clustering of bilateral plantar temperature variability, and plantar infrared image symmetry. Associations were tested using χ² or Fisher's exact tests and multivariable logistic/Cox models.</p><p><strong>Results: </strong>Our findings show that PTDs in sensor recordings as well as PIRI asymmetry are associated with a higher incidence of a composite of AF and thromboembolic events. Overall, 45 patients experience AF (n = 26), stroke (n = 6), PE (n = 4) or PAD (n = 11). Event rates are higher in patients with PTDs (25.8% vs 11.5%; p = 0.09; exploratory trend). For the elevated temperature variability cluster, the adjusted OR reaches 13.5 [95% CI 3.8-58.6] (34.0% vs 9.9%; p = 0.003; adjusted HR 13.3 [95% CI 1.5-120.4]). In individuals with plantar infrared image asymmetry, the likelihood is 48.6% compared to 6.2% in the symmetry group (p < 0.0001).</p><p><strong>Conclusions: </strong>In patients with diabetes, plantar temperature downshifts are associated with thromboembolic risk constellation.</p>","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":"6 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148649917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A meta-learning method with reduced data requirements for training and updating deep learning models on wearable devices.","authors":"Alireza Amirshahi, Maedeh H Toosi, Siamak Mohammadi, Stefano Albini, Pasquale Davide Schiavone, Giovanni Ansaloni, Amir Aminifar, David Atienza","doi":"10.1038/s43856-026-01740-1","DOIUrl":"10.1038/s43856-026-01740-1","url":null,"abstract":"<p><strong>Background: </strong>Wearable systems provide continuous health monitoring and can lead to early detection of potential health issues. However, the lifecycle of wearable systems faces several challenges. First, effective model training for new wearable devices requires substantial labeled data from various subjects collected directly by the wearable. Second, subsequent model updates require further extensive labeled data for retraining. Finally, frequent model updating on the wearable device can decrease the battery life in long-term data monitoring.</p><p><strong>Methods: </strong>Addressing these challenges, in this paper, we propose a meta-learning method to reduce the amount of initial data collection required. Moreover, our approach incorporates a prototypical updating mechanism, simplifying the update process by modifying the class prototype rather than retraining the entire model. We explore the performance of our proposed method in two case studies, namely, the detection of epileptic seizures and the detection of atrial fibrillation (AF).</p><p><strong>Results: </strong>We show that by fine-tuning with just a few samples, we achieve 70% and 82% AUC for the detection of epileptic seizures and the detection of AF, respectively. Compared to a conventional approach, our proposed method performs better with up to 45% AUC. Furthermore, updating the model with only 16 minutes of additional labeled data increases the AUC by up to 5.3%. Finally, the proposed method reduces the energy consumption for model updates by 456x and 418x for epileptic seizure and AF detection, respectively.</p><p><strong>Conclusions: </strong>Our findings demonstrate that the proposed method effectively overcomes the critical barriers of data scarcity and energy constraints, offering a practical and efficient solution for the lifecycle management of deep learning models on wearable health devices.</p>","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":"6 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13650112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149139611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FGL-1 plasma levels correlate with markers of inflammation and severe disease during SARS-CoV-2 infection.","authors":"Sophia Cichutek, Leon Cords, Kilian Keetz, Marissa Herrmann, Liz J Lam, Maria Mader, Robin Woost, Stefan Schmiedel, Ansgar W Lohse, Carsten Bokemeyer, Christoph Schultheiß, Marylyn M Addo, Walter Fiedler, Mascha Binder, Julian Schulze Zur Wiesch","doi":"10.1038/s43856-026-01775-4","DOIUrl":"10.1038/s43856-026-01775-4","url":null,"abstract":"<p><strong>Background: </strong>Fibrinogen-like protein 1 (FGL-1), primarily secreted by the liver, modulates immune responses and is upregulated in patients with hepatocellular carcinoma. FGL-1 affects T-cell function by interacting with lymphocyte-activation gene 3 (LAG-3), and blocking this interaction can enhance T-cell activity, making it a potential therapeutic target. In coronavirus disease 2019 (COVID-19), the upregulation of immune checkpoints on T cells, particularly LAG-3, is associated with disease severity. Liver inflammation and damage are well-known features of COVID-19 pathogenesis; however, little is known about FGL-1 expression patterns in COVID-19 and other infectious diseases.</p><p><strong>Methods: </strong>In a cohort of 65 patients with COVID-19 and 33 healthy donors, plasma FGL-1 levels were measured, and their correlations with clinical parameters and the course of the disease were evaluated. Additionally, both bulk and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-specific T-cell immune phenotypes, as well as SARS-CoV-2-specific immune responses were comprehensively characterized and measured using multicolor flow cytometry and pMHC multimer technology.</p><p><strong>Results: </strong>Plasma FGL-1 levels were elevated in patients with COVID-19 and correlated with IL-6 and disease severity. LAG-3 was significantly upregulated on bulk and COVID-19-specific CD8⁺ T cells and was co-expressed with T-cell activation markers (CD38, HLA-DR) and inhibitory receptors (PD-1, TIGIT).</p><p><strong>Conclusion: </strong>These findings suggest a role for FGL-1 in the pathogenesis of COVID-19, potentially through modulation of T-cell activation and function via LAG-3, and may also be relevant in other hyperinflammatory conditions where immune modulation plays a role.</p>","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":"6 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13469107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148725326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prenatal antifungal exposure disrupts fetal steroidogenesis and is associated with persistent effects in children.","authors":"Gylli Mola, Monica Kam Draskau, Anne Jørgensen, Frédéric Chalmel, Cecilie Melau, Bertrand Evrard, Karen Mandrup, Hanne Hegaard, Trine Koch Hueg, Hanne Frederiksen, Christa E Flück, Anna-Maria Andersson, Anders Juul, Kristian Almstrup, Margit Bistrup Fischer, Terje Svingen, Casper P Hagen","doi":"10.1038/s43856-026-01815-z","DOIUrl":"10.1038/s43856-026-01815-z","url":null,"abstract":"<p><strong>Background: </strong>Exposure to endocrine-disrupting chemicals (EDCs) during fetal life is associated with reproductive disorders in humans. While research has largely focused on environmental EDCs and developmental exposure, some pharmaceuticals, including commonly used antifungal agents, also possess endocrine-disrupting properties. We investigate whether prenatal exposure to over-the-counter antifungal drugs is associated with altered fetal and postnatal steroidogenesis and reproductive development.</p><p><strong>Methods: </strong>We combined epidemiological, experimental, and translational approaches using data from a prospective mother-child cohort (n = 589), ex vivo human fetal adrenal cultures, and in vivo rat models. Maternal antifungal use during pregnancy was assessed prospectively, and associations with fetal growth, anogenital distance (AGD), penile measurements, and circulating steroid hormone levels during infancy were evaluated. Experimental studies examined the effects of selected antifungal agents on steroidogenesis in cultured human fetal adrenals and gestationally exposed Sprague-Dawley rats.</p><p><strong>Results: </strong>Early-pregnancy antifungal exposure is associated with reduced circulating steroid hormone levels and indicators of diminished androgen action, including decreased penile width at infancy. In contrast, exposure during mid-to-late pregnancy is associated with elevated steroid hormone levels and longer AGD in both female fetuses and male infants. Consistent with these observations, the antifungal agent clotrimazole reduces progesterone levels in human fetal adrenal cultures and in gestationally exposed rats, whereas miconazole increases AGD in rats.</p><p><strong>Conclusions: </strong>These translational findings suggest that commonly used antifungal agents alter fetal adrenal steroidogenesis and influence reproductive development, with effects persisting into postnatal life. Given their widespread use and over-the-counter availability, the safety of topical azole use during pregnancy may warrant re-evaluation.</p>","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":"6 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13529680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148868193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety, feasibility, and preliminary clinical outcomes of psilocybin-assisted therapy for veterans with severe, treatment-resistant PTSD: an open-label pilot clinical trial.","authors":"Stacey B Armstrong, Adam W Levin, Nathan D Sepeda, Hillary Shaub, Taweh Hunter, Angela Douglas, Rafaelle Lancelotta, Alan K Davis","doi":"10.1038/s43856-026-01767-4","DOIUrl":"10.1038/s43856-026-01767-4","url":null,"abstract":"<p><strong>Background: </strong>Psilocybin-assisted therapy (PAT) shows promise for treating PTSD in adults but hasn't been studied in U.S. military Veterans, who face higher symptom severity and suicide risk.</p><p><strong>Methods: </strong>This open-label pilot trial evaluated the safety and feasibility of PAT in Veterans with severe, treatment-resistant PTSD. The clinical trial was pre-registered at ClinicalTrials.gov (NCT05554094). The eligibility criteria were that participants be U.S. military Veterans aged 21-64 with a DSM 5 diagnosis of PTSD for at least six months, and a Clinician-Administered PTSD Scale for DSM 5 (CAPS-5) total severity score ≥35. PTSD was also required to be treatment-resistant. Clinical outcomes were assessed at the Center for Psychedelic Drug Research and Education in Columbus, OH. Twelve participants received eight hours of therapy followed by two psilocybin dosing sessions at 15 mg and 25 mg, spaced 2-3 weeks apart, of synthetic psilocybin, along with approximately eight hours of post-psilocybin therapy. Follow-up occurred at four weeks post-second dosing. The primary endpoints were safety (i.e., the type, severity, frequency of adverse events) and suicidal ideation/behavior (as measured by the Columbia Suicide Severity Rating Scale (CSSR-S)) from baseline to 1-month post-second psilocybin administration. The secondary endpoints were PTSD symptom severity rated by a clinician and the participant. Exploratory analyses included the impact of psychotherapy and expectancy on PTSD symptom severity.</p><p><strong>Results: </strong>Of the 668 participants who completed the online pre-screener, 13 consented and enrolled, 1 withdrew before the first dosing session, and 12 fulfilled the study requirements. No serious adverse events occurred; non-serious adverse events included headaches, anxiety, and dizziness. There was no increase in suicidal ideation or behavior during the trial, and heart rate and blood pressure remained within safe limits during the psilocybin sessions. There was a large (d = 2.30) and significant (p < 0.001) reduction (mean difference = 27.5, 95% CI: 19.9 to 35.1) in clinician-rated PTSD symptoms from baseline through 1-month follow-up, with 75% having a treatment response and in remission from PTSD. While expectancy did not predict changes in PTSD symptoms, pre-dosing symptom change during the preparation phase of treatment did. Clinician adherence ratings were 98% across all study visits.</p><p><strong>Conclusions: </strong>Findings reveal that PAT is safe, well-tolerated, and shows preliminary clinical improvement for PTSD, suggesting that PAT may offer therapeutic relief for Veterans with severe treatment-resistant PTSD.</p>","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":"6 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13424359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148632996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Federated Learning Authenticity Standard for Healthcare as derived from lessons in self-driving cars.","authors":"Rui Santos, Pearse A Keane","doi":"10.1038/s43856-026-01820-2","DOIUrl":"10.1038/s43856-026-01820-2","url":null,"abstract":"","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":"6 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148649872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of respiratory disease hospitalisation forecasts using synthetic outbreak data.","authors":"Grégoire Béchade, Torbjörn Lundh, Philip Gerlee","doi":"10.1038/s43856-026-01802-4","DOIUrl":"10.1038/s43856-026-01802-4","url":null,"abstract":"<p><strong>Background: </strong>Forecasts of hospitalisations of infectious diseases play an important role for allocating healthcare resources during epidemics and pandemics. Large-scale analysis of model forecasts during the COVID-19 pandemic has shown that the model rank distribution with respect to accuracy is heterogeneous and that ensemble forecasts have the highest average accuracy.</p><p><strong>Methods: </strong>Building on that work we generated a maximally diverse synthetic dataset of 324 different hospitalisation time-series that correspond to different disease characteristics and public health responses. We evaluated forecasts from 14 component models and 6 different ensembles.</p><p><strong>Results: </strong>Our results show that component model accuracy was heterogeneous and varied depending on the current rate of disease transmission. Going from 7 day to 14 day forecasts mechanistic models improved in relative accuracy compared to statistical models. A novel adaptive ensemble method outperforms all other ensembles on synthetic data, and is closely followed by a median ensemble. When evaluated on data from the COVID-19 pandemic, component models performed worse, but the ensemble accuracy was still high, with the median ensemble performing best. We also investigated the relationship between ensemble error and variability of component forecasts and show that the coefficient of variation is predictive of future error.</p><p><strong>Conclusions: </strong>Our findings have the potential to improve epidemic forecasting, in particular the adaptive ensemble and the ability to assign confidence to ensemble forecasts at the time of prediction based on component forecast variability.</p>","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":"6 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13421584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148622739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing the HMG-CoA reductase inhibitor atorvastatin for SRD5A3-congenital disorder of glycosylation.","authors":"Hiba Daghar, Seul Kee Byeon, Claudia Maios, Jennifer Poon, James Doyle, Wasantha Ranatunga, Éric Samarut, Ethan O Perlstein, Eva Morava, Akhilesh Pandey, J Alex Parker, Kristin A Kantautas","doi":"10.1038/s43856-026-01791-4","DOIUrl":"10.1038/s43856-026-01791-4","url":null,"abstract":"<p><strong>Background: </strong>Steroid 5 alpha-reductase 3-related congenital disorder of glycosylation (SRD5A3-CDG) is a rare inherited disease characterized by neurological dysfunction, including ataxia, as well as developmental and visual impairments, with no approved treatments. The disease is caused by defects in dolichol biosynthesis, a pathway essential for protein glycosylation. However, the lack of suitable in vivo models has limited both mechanistic insight and therapeutic development.</p><p><strong>Methods: </strong>We generated a Caenorhabditis elegans model carrying a patient-relevant loss-of-function mutation and performed a motility-based phenotypic drug repurposing screen to identify compounds that improve disease-relevant phenotypes. Lead compounds were evaluated in behavioral, neuronal, and metabolomic assays in worms and in fibroblasts from four individuals with SRD5A3-CDG.</p><p><strong>Results: </strong>Here we show that SRD5A3-deficient worms exhibit developmental delay, neuronal dysfunction, and metabolic alterations consistent with dysregulation of the mevalonate pathway. The screen identifies multiple classes of compounds that improve motility, including the cholesterol-lowering drug atorvastatin. Atorvastatin improves multiple disease-relevant phenotypes in the worm model. In patient-derived fibroblasts, treatment partially restores the balance between polyprenol and dolichol, which is disrupted in SRD5A3-CDG.</p><p><strong>Conclusions: </strong>These findings establish an in vivo model of SRD5A3-CDG and identify modulation of the mevalonate pathway as a potential therapeutic strategy. The results support further investigation of atorvastatin as a repurposed treatment and demonstrate an approach for combining model organism screening with human cell validation to accelerate rare disease drug discovery.</p>","PeriodicalId":72646,"journal":{"name":"Communications medicine","volume":"6 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13642943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149119503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}