Sonia Podvin, Brin Rosenthal, Charles Mosier, Enlin Wei, Kathleen M Fisch, Vivian Hook
{"title":"Dysregulation of huntingtin interacting protein networks in human juvenile Huntington's disease brain.","authors":"Sonia Podvin, Brin Rosenthal, Charles Mosier, Enlin Wei, Kathleen M Fisch, Vivian Hook","doi":"10.1177/18796397251358348","DOIUrl":"https://doi.org/10.1177/18796397251358348","url":null,"abstract":"<p><p>BackgroundHuman Huntington's disease (HD) is a genetic neurodegenerative disorder caused by the mutant <i>HTT</i> gene containing CAG repeat expansions, resulting in motor dysfunction and behavioral deficits. CAG repeats of 40-53 occur in adult HD and 60-120 repeats occur in early onset juvenile HD, differing from the normal range of 5-35 repeats.ObjectiveThe <i>HTT</i> gene is translated to the huntingtin (HTT) protein that interacts with proteins in the development of HD. There have been few studies of HTT protein interactors in human HD brain. Therefore, this study evaluated the hypothesis that dysregulation of HTT protein interactors occurs in human juvenile HD brains.MethodsThe strategy of this study was to analyze proteomic data of human juvenile HD brain putamen and cortex regions for dysregulation of HTT interacting proteins, using a database that we compiled of HTT interactors identified in HD model systems from yeast to HD mice.ResultsResults showed significant dysregulation of HTT protein interactors of mitochondria, signal transduction, RNA splicing, chromatin organization, translation, membrane trafficking, endocytosis, vesicle, protein modification, granule membrane, and macroautophagy pathways. The majority of downregulated and upregulated HTT interactors occurred in the putamen region compared to cortex. Dysregulation displayed downregulation of mitochondria and signal transduction interactors, combined with upregulation of RNA splicing, chromatin organization, and translational interactors. Network analysis revealed interactions among clusters of HTT interactors.ConclusionsThese findings demonstrate prevalent dysregulation of HTT protein interactors in human juvenile HD brain, especially in the putamen region that controls movement deficits in HD.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"18796397251358348"},"PeriodicalIF":2.1,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jennifer Petrillo, Ruta Sawant, Rebecca Rogers, Sophie Cleanthous, Stefan Cano, Rajeev Kumar, Jennifer Klapper, Luis A Sierra, Jee Bang, Karen Elta Anderson, Deborah A Hall, Susan Perlman, Henry Moore, Danny Bega, Jason Johannesen, Emma Elliott
{"title":"Reliability and validity of the Huntington's Disease Everyday Functioning (Hi-DEF): A patient-reported measure of cognitive capacity on daily functioning in Huntington's disease.","authors":"Jennifer Petrillo, Ruta Sawant, Rebecca Rogers, Sophie Cleanthous, Stefan Cano, Rajeev Kumar, Jennifer Klapper, Luis A Sierra, Jee Bang, Karen Elta Anderson, Deborah A Hall, Susan Perlman, Henry Moore, Danny Bega, Jason Johannesen, Emma Elliott","doi":"10.1177/18796397251358375","DOIUrl":"https://doi.org/10.1177/18796397251358375","url":null,"abstract":"<p><p>BackgroundThe Huntington's Disease (HD) Everyday Functioning (Hi-DEF) is a novel patient-reported outcome (PRO) scale developed to assess the impact of cognitive impairment on daily functioning in early HD patients.ObjectiveTo examine the psychometric properties, including reliability and validity, of the Hi-DEF. Findings from psychometric analyses using classical test theory (CTT) approach are presented here.MethodsA non-interventional validation study was conducted across nine HD Centers of Excellence across the US.ResultsPatients with HD (n = 151) were recruited: 59% were female, mean (SD) age was 47 (12) years, and mean (range) Total Functional Capacity (TFC) score was 11.4 (8-13). Excellent internal consistency reliability was observed for the Hi-DEF scale total score (Cronbach's alpha: 0.98) and across subscales (alpha range 0.87-0.96). Most targeting and scaling assumptions were met, although there were ceiling effects for three subscales. Construct validity was demonstrated by moderate to high Spearman's rank-order correlations with TFC scores (range r = -0.38 to -0.62) and known and validated measures such as the HD-PRO-TRIAD<sup>TM</sup> (range r = 0.75-0.90), and ability to discriminate between levels of functional impairment (TFC 13, 12-11, and 10-8; <i>p</i> < 0.001). Correlations with Cambridge Neuropsychological Test Automated Battery (CANTAB) cognitive performance measures were low to moderate and ranged from 0.06 to 0.38.ConclusionsThe Hi-DEF is a reliable and valid PRO scale measuring the impact of cognitive impairment on daily functioning, assessing facets of cognitive functioning in context of activities of daily living impacted in early stages of HD.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"18796397251358375"},"PeriodicalIF":2.1,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Epidemiology and clinical features of Huntington's disease in MENASA region: A systematic review and meta-analysis.","authors":"Mehri Salari, Kamran Rezaei, Fatemeh Hojjati Pour, Mercedeh Sepehrnia, Masoud Etemadifar","doi":"10.1177/18796397251356620","DOIUrl":"https://doi.org/10.1177/18796397251356620","url":null,"abstract":"<p><p>BackgroundGiven the scarcity of comprehensive data on Huntington's disease in many Asian and African countries, it is more effective to focus on specific regions where there is a significant concentration of available data.ObjectiveThis study decided to evaluate the epidemiology and features of Huntington's disease in countries of the Middle East, North Africa, and South Asia (MENASA) regions.MethodsIn this meta-analysis, the limited maximum likelihood (REML) approach was applied to the estimated point prevalence mentioned in original studies of each MENASA country. Additionally, research on Huntington's disease characteristics in each nation was utilized to give a general picture of the disease's status in those nations.ResultsThe pooled point prevalence estimation of the prevalence studies was 8.64 per 100,000 (95% CI, -0.04-17.33; I<sup>2</sup> = 100%). Among 14 cohort and cross-sectional studies on individuals with Huntington's disease in the MENASA region, 5.61% of the patients had juvenile-onset Huntington's disease, and 2.3% had late-onset Huntington's disease. In addition, 68.58%, 17.82%, and 45.17% of the individuals were reported with motor symptoms at the onset, abnormal cognitive assessment scores, and degrees of psychological disturbance, respectively. The mean age at onset was 44.85 years, and the mean number of pathologic CAG repeats was 45.46.ConclusionsNotable differences in the frequency of symptoms of onset and pooled prevalence of HD in the MENASA region probably address a serious lack of sufficient information. The results would help clinicians and governments develop public health strategies, and further research could be conducted on these results.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"18796397251356620"},"PeriodicalIF":2.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Huntington disease and Beta-blocker drug use.","authors":"Peter A LeWitt, Bisena Bulica","doi":"10.1177/18796397251352042","DOIUrl":"https://doi.org/10.1177/18796397251352042","url":null,"abstract":"","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"18796397251352042"},"PeriodicalIF":2.1,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dysregulated astrocyte cholesterol synthesis in Huntington's disease: A potential intersection with other cellular dysfunctions.","authors":"Marta Valenza","doi":"10.1177/18796397251336192","DOIUrl":"https://doi.org/10.1177/18796397251336192","url":null,"abstract":"<p><p>Astrocytes are key elements for synapse development and function. Several astrocytic dysfunctions contribute to the pathophysiology of various neurodegenerative disorders, including Huntington's disease (HD), an autosomal-dominant neurodegenerative disorder that is characterized by motor and cognitive defects with behavioral/psychiatric disturbances. One dysfunction in HD related to astrocytes is reduced cholesterol synthesis, leading to a decreased availability of local cholesterol for synaptic activity. This review describes the specific role of astrocytes in the brain local cholesterol synthesis and presents evidence supporting a defective astrocyte-neuron cholesterol crosstalk in HD, by focusing on SREBP-2, the transcription factor that regulates the majority of genes involved in the cholesterol biosynthetic pathway. The emerging coordination of SREBP-2 with other physiological processes, such as energy metabolism, autophagy, and Sonic Hedgehog signaling, is also discussed. Finally, this review intends to stimulate future research directions to explore whether the impairment of astrocytic SREBP-2-mediated cholesterol synthesis in HD associates with other cellular dysfunctions in the disease.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"18796397251336192"},"PeriodicalIF":2.1,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kasper Frederik van der Zwaan, Raymund Ac Roos, Susanne T de Bot
{"title":"Anosognosia and avoidant coping do not impact work in early Huntington's disease.","authors":"Kasper Frederik van der Zwaan, Raymund Ac Roos, Susanne T de Bot","doi":"10.1177/18796397251349114","DOIUrl":"10.1177/18796397251349114","url":null,"abstract":"<p><p>BackgroundWork plays a crucial role in life, contributing to financial stability and well-being. Huntington's disease (HD), a genetic neurodegenerative disorder, can significantly affect work capacity. Anosognosia (lack of awareness of impairments) and avoidant coping are common in HD but remain unexplored in relation to work outcomes.ObjectiveThis study investigated the relationships between anosognosia, coping styles, and work capacity in individuals with pre-motor manifest and motor manifest HD.MethodsUtilizing the HD-Work dataset, we analyzed motor and cognitive functioning, coping styles, work capacity, and anosognosia in participants with pre-motor manifest and motor manifest HD (n = 117). Anosognosia was operationalized through expert rating, participant - proxy, and cognitive - performance discrepancies. Work capacity was measured using the occupation item of the Total Functional Capacity scale, and coping styles were assessed with the <i>Utrechtse Coping Lijst</i>.ResultsAnosognosia was strongly associated with cognitive decline, while avoidant coping was less prevalent. Both anosognosia and avoidance coping were correlated with frontal behaviors but not with work capacity. A positive association between avoidant coping and anosognosia was found. The most common coping style used was passive coping. Participants did not often seek social comfort.ConclusionsThe best predictor of anosognosia was cognitive decline. The positive association between avoidant coping and anosognosia suggested a potential misattribution of avoidant coping to anosognosia. This study emphasized the importance of recognizing avoidant and passive coping strategies in early-stage HD, as well as anosognosia in relation to cognitive decline, even though these factors do not directly impact work capacity.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"179-190"},"PeriodicalIF":2.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12231776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266423","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}
Eardi Lila, David Hunt, Daniel D Child, Caitlin Latimer, Bianca Le, Marie Davis, Suman Jayadev, Thomas D Bird, Ali Shojaie, Christine L Mac Donald
{"title":"Asymmetric brain atrophy in Huntington's disease: A postmortem MRI study.","authors":"Eardi Lila, David Hunt, Daniel D Child, Caitlin Latimer, Bianca Le, Marie Davis, Suman Jayadev, Thomas D Bird, Ali Shojaie, Christine L Mac Donald","doi":"10.1177/18796397251333334","DOIUrl":"10.1177/18796397251333334","url":null,"abstract":"<p><p>BackgroundHuntington's disease is a progressive, autosomal dominant, neurodegenerative disease caused by a CAG repeat expansion in the HTT gene. Medium spiny neurons of the striatum are especially vulnerable to the disease, and atrophy of the caudate and putamen can be documented by neuroimaging years before the onset of symptoms.ObjectiveIn this study, we aimed to characterize region-specific gray and white matter differences between Huntington's disease patients and controls.MethodsWe conducted a postmortem MRI study of the brains of 15 adults diagnosed with symptomatic Huntington's disease and 26 control subjects, aiming to compare the differences in regional grey and white matter volumes between the two groups.ResultsThe study revealed decreased volumes in both grey and white matter in patients with Huntington's disease, with the largest effect sizes observed in caudate and putamen. Notably, the atrophy predominantly affected the left hemisphere, particularly impacting grey and white matter regions adjacent to the pars opercularis, precentral, supramarginal, and pars orbitalis gyri, and the lateral orbitofrontal cortex. In the control group, asymmetry stems from larger left hemisphere regions compared to right, whereas an opposite pattern is observed in the Huntington's disease group.ConclusionsThese results suggest progressive, diffuse, and asymmetric grey and white matter atrophy occurs in Huntington's disease. The reasons for this asymmetry remain unknown; however, our study provides a more detailed characterization of previously reported grey and white matter changes in Huntington's disease, as observed through postmortem histopathological and MRI studies.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"132-139"},"PeriodicalIF":2.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rebecca Lm Fuller, Pua Feigenbaum, Nancy LaPelle, Swati Sathe, Prachi Dalal, Jatin G Vaidya, Neha Sinha, Matthew Roché, Cheryl J Fitzer-Attas, Cristina Sampaio, Glenn T Stebbins
{"title":"Functional Rating Scale 2.0 (FuRST 2.0): A patient-reported outcome measure of function for Huntington's disease.","authors":"Rebecca Lm Fuller, Pua Feigenbaum, Nancy LaPelle, Swati Sathe, Prachi Dalal, Jatin G Vaidya, Neha Sinha, Matthew Roché, Cheryl J Fitzer-Attas, Cristina Sampaio, Glenn T Stebbins","doi":"10.1177/18796397251323549","DOIUrl":"10.1177/18796397251323549","url":null,"abstract":"<p><p>BackgroundCurrent functional rating scales are not sensitive to the earliest functional changes in Huntington's disease (HD).ObjectiveThe Functional Rating Scale 2.0 (FuRST 2.0) is a patient-reported outcome (PRO) measure designed to be sensitive to the initial functional changes in HD, specifically stage 2 and mild stage 3, as defined by the Huntington's Disease Integrated Staging System (HD-ISS).MethodsWe followed standard assessment development methodology to create a PRO. Study 1 consisted of a Delphi panel which analyzed data from focus groups comprised of people with HD and companions from 6 countries. This was followed by four rounds of cognitive interviews through which we evaluated respondents' comprehension of the instructions, understanding of question and response options, and comfort with the material. Informal advice from a regulatory agency was garnered throughout the process.ResultsConcerns from the target population and regulators regarding instructions, questions, response options, and comfort with the material were addressed through modifications to the scale's wording and format.ConclusionsWe developed the FuRST 2.0 official working document (OWD), the penultimate version of the scale, using focus groups, a Delphi panel, iterative rounds of cognitive interviewing, and informal regulatory advice. Its psychometric properties are being evaluated in the FOCUS-HD validation studies from which the final version of the scale will be derived. The FuRST 2.0 OWD is available for use.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"171-178"},"PeriodicalIF":2.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12231842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144022283","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}
Kayla Dodson, Sabrina Livezey, Brittany Denson, Leena Choi, Josh DeClercq, Autumn D Zuckerman, Kayla Johnson
{"title":"Deutetrabenazine treatment outcomes with doses above U.S. Food and Drug Administration maximum approved doses in Huntington's disease chorea: A dual-site analysis.","authors":"Kayla Dodson, Sabrina Livezey, Brittany Denson, Leena Choi, Josh DeClercq, Autumn D Zuckerman, Kayla Johnson","doi":"10.1177/18796397251323293","DOIUrl":"10.1177/18796397251323293","url":null,"abstract":"<p><p>BackgroundDeutetrabenazine, a vesicular monoamine transporter 2 inhibitor, is one of few treatment options available for Huntington's disease (HD) chorea. There is limited data describing clinical experience with deutetrabenazine doses >48 mg daily.ObjectiveDescribe treatment outcomes for deutetrabenazine >48 mg daily.MethodsA dual site retrospective cohort study of patients on deutetrabenazine titrated to doses >48 mg/day for HD chorea from April 2017 through December 2021 was conducted. Patients using concomitant strong CYP2D6 inhibitors at time of deutetrabenazine initiation, those who became deceased or lost to follow-up within six months of dose increase above 48 mg/day, or previously enrolled in a study on >48 mg daily and moving to commercial product were excluded. Outcomes were reported descriptively including therapeutic response, adverse effects (AEs), adherence (measured by proportion of days covered [PDC]), and discontinuation.ResultsThirty patients were included: 47% female, 93% White, median age 56 years. Most patients required dose escalations for inadequate response. The rate of AEs reported before and after transitioning to doses >48 mg/day was the same. Psychiatric changes were less commonly reported at doses >48 mg/day, but extrapyramidal symptoms were more common. The median total maximum chorea score in the Unified HD Rating Scale was 13 (IQR 9-19) and 13 (IQR 7-18) at baseline and follow-up, respectively. Median PDC was 0.99 (IQR 0.94-1.00); two patients discontinued therapy due to AEs.ConclusionsDeutetrabenazine >48 mg daily appears safe and well tolerated in patients with uncontrolled HD chorea, though no significant change in total maximal chorea score was found.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"140-148"},"PeriodicalIF":2.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tayela M Prichard, Cali M Roiboit, Meg E Rankin, Yifat Glikmann-Johnston, Mark F Gordon, Julie C Stout
{"title":"A systematic review of performance-based functional capacity measures for use in Huntington's disease and evaluation of their suitability for clinical trials.","authors":"Tayela M Prichard, Cali M Roiboit, Meg E Rankin, Yifat Glikmann-Johnston, Mark F Gordon, Julie C Stout","doi":"10.1177/18796397251330846","DOIUrl":"10.1177/18796397251330846","url":null,"abstract":"<p><p>BackgroundHuntington's disease (HD) leads to a decline in functional capacity, affecting daily life tasks. Assessing functional capacity in clinical trials is crucial to evaluate treatment effectiveness and substantiate the clinical meaningfulness of more sensitive and reliable measures. Clinician rating scales are commonly used, but performance-based measures of functional capacity may offer advantages, however, there is no consensus on the suitability of existing performance-based measures for use in HD.ObjectiveWe applied a Consensus-based Standards for the selection of health Measurement INstruments (COSMIN) approach to evaluate the potential suitability of performance-based functional capacity measures for HD clinical trials. We also used criteria developed with expert input to assess these measures.MethodsWe conducted a systematic search of relevant databases and screened 1924 articles for inclusion criteria.ResultsWe included a total of 89 articles on 33 performance-based functional capacity measures. Measures were rated from Very Low to Moderate suitability for use in HD clinical trials. DriveSafe DriveAware and EcoKitchen were the only measures tested in HD participants and were rated as having Moderate and Very Low suitability respectively, highlighting the need for further evaluation. Additionally, the Brief University of California San Diego Performance-based Skills Assessment (UCSD UPSA-B) and the Virtual Reality Functional Capacity Assessment Tool (VRFCAT), were identified as potentially useful, also rated Moderate.ConclusionsMultiple performance-based functional capacity measures show potential for use in patients with HD, pending further investigation.</p>","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"113-131"},"PeriodicalIF":2.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12231780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780266","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}