Journal of Inherited Metabolic Disease最新文献

{"title":"Tailored Amino Acid Treatment for Pediatric Patients With Mitochondrial Aminoacyl-tRNA Synthetase Deficiencies","authors":"I. J. J. Muffels,&nbsp;G. Kok,&nbsp;Z. Tang,&nbsp;L. S. Medeiros,&nbsp;F. O. Poswar,&nbsp;W. P. Vermeij,&nbsp;R. Rodenburg,&nbsp;K. Smit,&nbsp;S. K. Sukumaran,&nbsp;S. B. Wortmann,&nbsp;L. Averdunk,&nbsp;J. Munch,&nbsp;J. Pak-lam Ho,&nbsp;A. M. K. Kwok,&nbsp;E. E. S. Nieuwenhuis,&nbsp;P. M. van Hasselt,&nbsp;I. V. D. Schwartz,&nbsp;C. M. A. Lubout,&nbsp;A. M. Bosch,&nbsp;K. Koop,&nbsp;E. M. M. Hoytema van Konijnenburg,&nbsp;S. A. Fuchs","doi":"10.1002/jimd.70254","DOIUrl":"10.1002/jimd.70254","url":null,"abstract":"<p>Aminoacyl-tRNA synthetases (ARSs) facilitate the loading of transfer RNAs with their cognate amino acids in the cytosol (ARS1), mitochondria (ARS2), or both (dual ARS). ARS deficiencies are clinically heterogeneous and can cause severe, occasionally fatal disease. Supplementation with cognate amino acids to prevent local amino acid depletion has shown promise in ARS1 deficiencies, but its potential in ARS2 deficiencies remains largely unexplored. We investigated the effects of cognate amino acid depletion on mitochondrial function in fibroblasts from seven patients with ARS2 deficiencies using Seahorse respirometry and imaging flow cytometry. During amino acid depletion, patient fibroblasts showed decreased mitochondrial membrane potential and reduced basal and maximal respiratory capacity. We additionally evaluated oral cognate amino acid supplementation in nine patients with SARS2, EARS2, LARS2, WARS2, FARS2, or VARS2 deficiencies. Supplementation was well tolerated, with no adverse effects observed. Several patients showed clinical improvements during treatment, including improved development, increased growth, and/or improved cardiac function. In two patients, treatment discontinuation coincided with severe neurological regression. Together, these findings demonstrate that assessing mitochondrial function during cognate amino acid depletion provides a novel functional assay for ARS2 deficiencies that may aid variant interpretation and supports a biological rationale for cognate amino acid supplementation. Clinical supplementation was well tolerated and showed preliminary beneficial effects. These findings support further investigation of cognate amino acid supplementation as a potential supportive treatment strategy for patients with ARS2 deficiencies.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"49 6","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting Inherited Metabolic Diseases (IMDs) Through the Lens of Selective Autophagy","authors":"Marianna Maddaluno,&nbsp;Laura Cinque,&nbsp;Viviana Cetrangolo,&nbsp;Chiara De Leonibus","doi":"10.1002/jimd.70259","DOIUrl":"10.1002/jimd.70259","url":null,"abstract":"<p>Selective autophagy is increasingly recognized as a fundamental quality-control mechanism that complements bulk autophagy by enabling the targeted degradation of specific intracellular cargos, including mitochondria, endoplasmic reticulum (ER), lipid droplets, glycogen, peroxisomes, ferritin, ribosomes, and protein aggregates. Cargo selectivity is mediated by selective autophagy receptors (SARs), which link damaged or superfluous substrates to the autophagic machinery through LC3/GABARAP interactions, thereby coordinating cargo sequestration. Recent studies have revealed substantial mechanistic differences between bulk and selective autophagy, highlighting the specialized signaling pathways, receptor networks, and transcriptional programs that regulate selective cargo clearance. Dysregulation of these pathways has emerged as a key contributor to the pathogenesis of inherited metabolic diseases (IMDs), a heterogeneous group of genetic disorders characterized by defective metabolism and multisystem involvement. This review summarizes the molecular mechanisms underlying major forms of selective autophagy, including mitophagy, pexophagy, glycophagy, lipophagy, ER-phagy, and ferritinophagy. It also discusses their relevance across IMD classes, such as mitochondrial disorders, lysosomal storage disorders, and peroxisomal diseases, among many others. Furthermore, selective autophagy is highlighted as a potential therapeutic target, with modulation of autophagy receptors and signaling pathways offering promising strategies to restore cellular homeostasis and improve disease manifestations in IMDs.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"49 6","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dichloroacetate Improves Animal Survival, Growth, Neuromuscular Activity, Mitochondrial Stress and Physiology, and Elevated Lactate in C. elegans pdha-1 and dld-1 RNAi Models of Pyruvate Dehydrogenase Complex Deficiency (PDCD)","authors":"Cristina Remes,&nbsp;Neal D. Mathew,&nbsp;Victoria Miranda,&nbsp;Suraiya Haroon,&nbsp;Tyler O'Hara,&nbsp;Vernon E. Anderson,&nbsp;Manuela Lavorato,&nbsp;Kelsey Keith,&nbsp;Rui Xiao,&nbsp;Eiko Nakamaru-Ogiso,&nbsp;Marni J. Falk","doi":"10.1002/jimd.70257","DOIUrl":"10.1002/jimd.70257","url":null,"abstract":"<p>Pyruvate dehydrogenase complex (PDHc) deficiency (PDCD) is a primary mitochondrial disorder characterized by neurodevelopmental disability, altered intermediary metabolism, and early mortality. Dichloroacetate (DCA), a pyruvate analog, activates PDHc and remains under clinical investigation for treatment of PDCD. Here, we studied the in vivo efficacy of a five-point log concentration range of DCA on animal health and metabolism in <i>C. elegans</i> with feeding RNA interference (RNAi) expression knockdown of either <i>PDHA-1</i> or <i>DLD-1</i> homologs at graded degrees to model variable disease severity. These worm models recapitulate phenotypic features of PDCD observed in human patients, including reduced survival, delayed growth, locomotor impairment, and elevated lactate and/or pyruvate tissue levels. DCA treatment appeared well-tolerated, with no gross morphologic toxicity seen at doses up to 25 mM. Significantly improved health, survival, tissue lactate levels, and mitochondrial physiology were observed at 25 mM in <i>pdha-1(RNAi)</i> knockdown animals. DCA treatment in <i>dld-1(RNAi)</i> <i>C. elegans</i> models (undiluted, 1:20 dilution, and 1:100 dilution) significantly improved survival, neuromuscular function, and metabolic phenotypes primarily in the moderate (1:20) and/or mild (1:100) <i>dld-1(RNAi)</i> deficiency strains, but not in full-dose <i>dld-1(RNAi)</i>. Importantly, linear growth, neuromuscular activity, and mitochondrial physiology were significantly improved with DCA treatment even in the most severe <i>dld-1(RNAi)</i> undiluted model. Overall, preclinical modeling provides objective evidence of DCA therapeutic efficacy in <i>C. elegans</i> knockdown strains for two well-conserved homologs of <i>PDHA1</i> and <i>DLD</i> representing distinct genetic etiologies of PDCD, with demonstrated beneficial effects on survival, healthspan, tissue lactate, and mitochondrial physiology. These data further confirm that DCA's therapeutic effect correlates with PDHc disease phenotype severity in <i>dld-1(RNAi)</i> animals.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"49 6","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70257","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obituary for Prof. Marcello Giovanni","authors":"Enrica Riva,&nbsp;Giacomo Biasucci,&nbsp;Elvira Verduci","doi":"10.1002/jimd.70258","DOIUrl":"https://doi.org/10.1002/jimd.70258","url":null,"abstract":"","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"49 6","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70258","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149145971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Consensus Guidelines for Diagnosis and Management of Pyruvate Dehydrogenase Complex Deficiency","authors":"Nandaki Keshavan,&nbsp;Julia Neugebauer,&nbsp;Marcello Bellusci,&nbsp;Enrico Bertini,&nbsp;Garry Brown,&nbsp;Niklas Darin,&nbsp;Suzanne DeBrosse,&nbsp;Lucy Drexler,&nbsp;Stefan Drexler,&nbsp;Gregory M. Enns,&nbsp;Rebecca D. Ganetzky,&nbsp;Kelly Gilbert,&nbsp;Austin Larson,&nbsp;Rebecca Legi,&nbsp;April N. Lehman,&nbsp;Camile Newby,&nbsp;Manuel Schiff,&nbsp;Rachel Skeath,&nbsp;Peter W. Stacpoole,&nbsp;Sarah Thompson,&nbsp;Emma Watt,&nbsp;Saskia B. Wortmann,&nbsp;Jirair K. Bedoyan,&nbsp;Shamima Rahman","doi":"10.1002/jimd.70226","DOIUrl":"10.1002/jimd.70226","url":null,"abstract":"<p>Primary pyruvate dehydrogenase complex deficiency (PDCD) comprises a group of monogenic disorders caused by pathogenic variants in genes encoding subunits of, or regulatory components affecting, the pyruvate dehydrogenase complex. The clinical phenotype spans a broad continuum, ranging from early onset congenital lactic acidosis to infantile or childhood onset global developmental delay with epilepsy, through to more attenuated adult-onset neurological presentations. Reports from patients and advocacy groups indicate substantial variability in clinical management across both emergency and outpatient settings and between centres internationally. This variability underscores the need for systematic evaluation of the evidence base and the development of harmonised, consensus-driven clinical guidelines to standardise care and improve outcomes. An international consortium of experts from Europe and North America, including metabolic physicians, neurologists, dietitians, geneticists and patient representatives, was convened. The group undertook a structured review of the literature and developed guideline statements addressing disease classification, recognition, diagnostic evaluation, dietary and non-dietary management, surveillance for complications, genetic counselling and transition to adult services. Each recommendation was assigned a GRADE rating reflecting strength and quality of evidence. Consensus was achieved using a Delphi methodology. In total, 199 recommendations reached consensus and constitute the core of these guidelines. These recommendations provide a framework for consistent, high-quality, multidisciplinary care. The process also identified key evidence gaps, highlighting priorities for future research and the ongoing need to develop effective disease-modifying therapies.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"49 6","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13631685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149110838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Congenital Disorders of Glycosylation (CDG): State of the Art in 2026","authors":"Patryk Lipiński,&nbsp;Jaak Jaeken","doi":"10.1002/jimd.70256","DOIUrl":"https://doi.org/10.1002/jimd.70256","url":null,"abstract":"<div>\u0000 \u0000 <p>Congenital disorders of glycosylation (CDG) are a rapidly expanding group of inherited metabolic diseases affecting glycoconjugate glycan biosynthesis and attachment. This review provides a structured overview of major advances in human CDG reported from 2023 to 2026, including newly recognized CDG, emerging biochemical and pathophysiological insights, advances in diagnostic strategies and biomarkers, and progress in treatment. Recent developments include the recognition of RPN1-CDG, UGGT1-CDG, and DHRSX-CDG, refinement of phenotypes in established disorders, including PMM2-CDG, ALG13-CDG, ALG8-CDG, GMPPA-CDG, TRAPPC11-CDG, and PGAP3-CDG, and increasing use of glycomics, glycoproteomics, cellular models, and multi-omics approaches. Therapeutic progress remains uneven: no FDA/EMA-approved disease-modifying therapy is currently available for any CDG, and most interventions remain off-label, experimental, or supported by limited observational evidence. Despite substantial progress, most CDG still lack disease-modifying treatment, validated biomarkers, and prospective natural history data.</p>\u0000 </div>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"49 6","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149072662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Essential Oral Single Nutritional Therapy Products for Inherited Metabolic Diseases: Evidence and Consensus Assessment Using a Modified Delphi Method","authors":"Nina N. Stolwijk,&nbsp;Bart M. F. Penninx,&nbsp;Annet M. Bosch,&nbsp;Mirjam Langeveld,&nbsp;Gajja S. Salomons,&nbsp;Carla E. M. Hollak,&nbsp;Essential Nutritional Therapy Products for IMDs Consensus Group","doi":"10.1002/jimd.70252","DOIUrl":"https://doi.org/10.1002/jimd.70252","url":null,"abstract":"<p>Nutritional therapy is critical in managing inherited metabolic diseases (IMDs), and includes specialized diets and single nutritional therapy products (sNTPs) such as vitamins, cofactors, and amino acids. Many sNTPs function as medicines, but are regulated as food (e.g., food supplements), which can limit access, reimbursement, and consistent supply. Essential medicines, as defined by World Health Organization (WHO), meet key healthcare needs and must be available, affordable, and quality-assured. Some sNTPs might meet this threshold, supporting their potential inclusion in the WHO essential medicines list. A modified Delphi process was conducted with a panel of 36 experts from 18 European countries to identify which sNTPs are essential for IMD treatment. Ninety-six sNTPs and their target IMDs were assessed using a literature-informed five-criteria framework, that included evaluation of the level of scientific evidence for usefulness and effectiveness. Overall, 31 sNTPs were deemed essential in the management of 55 IMDs, consisting of vitamins (<i>n</i> = 12), minerals (<i>n</i> = 4), amino acids (<i>n</i> = 6), sugars (<i>n</i> = 2), and other nutrients (<i>n</i> = 7). Evidence supporting their use ranged from levels 3 to 4 of the Oxford Centre for Evidence-Based Medicine (OCEBM), reflecting the limited clinical trial data inherent to rare diseases. Seven of these are already included in the WHO essential medicines list. Recognition of the remaining 24 essential sNTPs could improve their availability and reimbursement, and in some cases, may warrant formal authorization as medicines. Subsequent research should focus on access inequities, cost barriers, and incorporate patient perspectives to optimize the use and impact of sNTPs in IMD management.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"49 6","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70252","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149072663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment of Fatty Acid Oxidation Disorders Today: Emerging Personalized Treatment Strategies","authors":"U. Spiekerkoetter,&nbsp;J. Vockley","doi":"10.1002/jimd.70255","DOIUrl":"10.1002/jimd.70255","url":null,"abstract":"<p>The first international guideline on treatment and management of long-chain fatty acid oxidation disorders has been published and demonstrates little scientific evidence for many of the treatment decisions. However, it is a substantial achievement to harmonize treatment and to define the remaining challenges. We here deliver some thoughts on this guideline and highlight the tremendous effort to reach this international consensus.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"49 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70255","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct Urea Cycle Dysfunction Profiles Differentiate Acute Metabolic Decompensation in TMEM70 and MT-ATP6-Related Mitochondrial ATP Synthase Defects","authors":"Barbara Siri,&nbsp;Diego Martinelli,&nbsp;Rosalba Carrozzo,&nbsp;Sara Boenzi,&nbsp;Sara Cairoli,&nbsp;Cristiano Rizzo,&nbsp;Teresa Giovanniello,&nbsp;Johannes Häberle,&nbsp;Carlo Dionisi-Vici","doi":"10.1002/jimd.70244","DOIUrl":"10.1002/jimd.70244","url":null,"abstract":"<div>\u0000 \u0000 <p>ATP synthase defects, including TMEM70 and MT-ATP6 deficiencies, cause severe mitochondrial encephalo-(cardio)-myopathies complicated by acute metabolic decompensations (AMDs) often associated with hyperammonaemia. However, detailed biochemical characterisation of these events remains limited. The aim of the study was to evaluate the metabolic profiles associated with TMEM70 and MT-ATP6 deficiencies during AMDs in comparison to stable metabolic conditions, assessing frequency and severity of hyperammonaemia, and exploring the mechanisms linking impaired mitochondrial ATP production to the urea cycle by in vivo ureagenesis studies, using [¹⁵N] ammonium chloride as stable isotope and assessed by high-resolution mass-spectrometry coupled with liquid chromatography. We retrospectively analysed clinical and biochemical profiles from two genetically confirmed cohorts. Patients with TMEM70 deficiency experienced more frequent AMDs, often with hyperammonaemia and requiring extracorporeal detoxification, while the MT-ATP6 cohort had more prominent neurological symptoms and a lower incidence of hyperammonaemia. Biochemically, both groups showed elevated lactate, alanine and glutamine, with orotic aciduria and abnormalities in purine/pyrimidine metabolism. Plasma citrulline levels were divergent in the two cohorts, with a consistent reduction in patients with MT-ATP6 deficiency and normal or borderline elevated levels in the TMEM70 cohort. In vivo stable isotope studies pointed to the differential impact of TMEM70 and MT-ATP6 deficiency on ureagenesis and on the enrichment of individual urea cycle-related amino acids. This study reveals that TMEM70 and MT-ATP6 deficiencies share features of mitochondrial dysfunction but present distinct metabolic profiles, highlighting a different impact on the urea cycle and its related metabolites, and providing novel insights on our understanding of mitochondrial pathophysiology.</p>\u0000 </div>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"49 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148930018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome Editing for Glycogen Storage Diseases","authors":"Troy von Beck,&nbsp;Raymond Wang,&nbsp;Dwight Koeberl","doi":"10.1002/jimd.70249","DOIUrl":"10.1002/jimd.70249","url":null,"abstract":"<p>Gene therapy has been developed for several glycogen storage diseases and has advanced into clinical trials. However, the limitations of these gene therapies with regard to stability following treatment early in life have led to the development of genome editing. Early results for genome editing in both glycogen storage disease type Ia and Pompe disease have demonstrated promising efficacy, and proof-of-concept studies as well as a clinical trial are underway. These studies will determine whether genome editing fulfills its promise with regard to stably treating glycogen storage diseases early in life.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"49 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13551056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}