Quantifying neurologic disease using biosensor measurements in-clinic and in free-living settings in multiple sclerosis

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Technological advances in passive digital phenotyping present the opportunity to quantify neurological diseases using new approaches that may complement clinical assessments. Here, we studied multiple sclerosis (MS) as a model neurological disease for investigating physiometric and environmental signals. The objective of this study was to assess the feasibility and correlation of wearable biosensors with traditional clinical measures of disability both in clinic and in free-living in MS patients. This is a single site observational cohort study conducted at an academic neurological center specializing in MS. A cohort of 25 MS patients with varying disability scores were recruited. Patients were monitored in clinic while wearing biosensors at nine body locations at three separate visits. Biosensor-derived features including aspects of gait (stance time, turn angle, mean turn velocity) and balance were collected, along with standardized disability scores assessed by a neurologist. Participants also wore up to three sensors on the wrist, ankle, and sternum for 8 weeks as they went about their daily lives. The primary outcomes were feasibility, adherence, as well as correlation of biosensor-derived metrics with traditional neurologist-assessed clinical measures of disability. We used machine-learning algorithms to extract multiple features of motion and dexterity and correlated these measures with more traditional measures of neurological disability, including the expanded disability status scale (EDSS) and the MS functional composite-4 (MSFC-4). In free-living, sleep measures were additionally collected. Twenty-three subjects completed the first two of three in-clinic study visits and the 8-week free-living biosensor period. Several biosensor-derived features significantly correlated with EDSS and MSFC-4 scores derived at visit two, including mobility stance time with MSFC-4 z-score (Spearman correlation −0.546; p = 0.0070), several aspects of turning including turn angle (0.437; p = 0.0372), and maximum angular velocity (0.653; p = 0.0007). Similar correlations were observed at subsequent clinic visits, and in the free-living setting. We also found other passively collected signals, including measures of sleep, that correlated with disease severity. These findings demonstrate the feasibility of applying passive biosensor measurement techniques to monitor disability in MS patients both in clinic and in the free-living setting.

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  • Research Article
  • Cite Count Icon 78
  • 10.1097/wno.0000000000000057
Retinal Nerve Fiber Layer Thickness, Brain Atrophy, and Disability in Multiple Sclerosis Patients
  • Mar 1, 2014
  • Journal of Neuro-Ophthalmology
  • Jose Manuel Abalo-Lojo + 6 more

To study the relationship between retinal nerve fiber layer (RNFL) thickness and brain atrophy using magnetic resonance imaging (MRI) with bicaudate ratio (BCR) in patients with multiple sclerosis (MS) with different levels of disease severity. We also assessed whether RNFL thickness correlated with Expanded Disability Status Scale (EDSS) score. The participants consisted of 88 patients with MS and 59 age- and sex-matched healthy control subjects. Eleven patients had clinically isolated syndrome (CIS), 68 patients had relapsing-remitting MS (RR-MS), and 9 patients had secondary progressive MS. Patients and controls were evaluated using optical coherence tomography (OCT, Cirrus) and scanning laser polarimetry with variable corneal compensation (GDx VCC). Patients underwent the same brain MRI scanning protocol. Disability was evaluated according to the EDSS. The BCR was calculated by dividing the minimum intercaudate distance by brain width along the same level. The BCR was higher in patients with MS (0.12 ± 0.03) than in controls (0.08 ± 0.009) (P < 0.001). OCT average RNFL thickness in patients with MS was significantly lower (84.51 ± 14.27 μm) than in control subjects (98.44 ± 6.83 μm). BCR was correlated with OCT average RNFL thickness (r = -0.48, P = 0.002) in patients with MS without optic neuritis. Significant correlations were found between average RNFL thickness and EDSS (r = -0.43, P = 0.003). Additionally, there were correlations between BCR with GDx parameters in patients with MS without optic neuritis. This study shows that RNFL thickness correlates with BCR and with MS subtypes. Additionally, our study indicates that OCT is better suited for MS assessment than GDx. We conclude that the damage of retinal axons appears related to brain damage in patients with MS.

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  • 10.3760/cma.j.issn.1671-8925.2014.06.015
Quantitative study of corpus callosum segmentation MRI topology and brain white matter tractography in patients with multiple sclerosis
  • Jun 15, 2014
  • Chinese Journal of Neuromedicine
  • Bing Hu + 5 more

Objective To observe the quantitative corpus callosum (CC) segmentation MRI topology and brain white matter tractography variations in patients with multiple sclerosis (MS),and to assess the correlation between quantitative indicators and scores of expanded disability status scale (EDSS).Methods Conventional MRI and diffusion tensor imaging (DTI) were applied in 32 MS patients and 32 healthy volunteers,admitted to our hospital from June 2011 to June 2013.The areas,average diffusion coefficent (ADC) values,fractional anisotropy (FA) values and tracked lines of each CC segment (1-5) and total CC were measured.T tests were used to compare the above quantitative indices in MS patients with those in controls.Linear regression model was used to determine the relationship between quantitative indices and scores of EDSS in MS patients.Results Various degrees of damage of white matter tracts in CC of MS patients could be visually identified by tractography.The areas,FA values and tracked lines of each CC segment in MS patients were smaller than those in controls (P<0.05),and the ADC values of segment 1-3 in MS patients were larger than those in controls (P<0.05).Moreover,the areas ([549.13±64.07] mm2),FA values (0.55±0.05) and tracked lines (519.78±79.03) of total CC in MS patients were smaller than those in controls ([614.56±39.67] mm2,[0.67±0.02] and [612.34±39.51],P<0.05),and the ADC values ([0.93±0.09]×10-3 mm2/s) of total CC in MS patients were larger than those in controls ([0.86±0.03]×10-3 mm2/s,P<0.05).Both areas and tracked lines of each CC segment in MS patients had negative correlations with EDSS scores (P<0.05).Moreover,both areas and tracked lines of total CC in MS patients were found having negative correlations with EDSS scores (r=-0.686,P=0.000;r=-0.676,P=0.000).Conclusion Both areas and tracked lines of each CC segment and total CC reflect the degrees of clinical disability in MS patients,which can be used for disease and efficacy evaluation of MS patients. Key words: Multiple sclerosis; Corpus callosum; MRI; Diffusion tensor imaging; brain white matter tractography

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  • Cite Count Icon 1
  • 10.5937/scriptamed51-27558
Prognostic significance of intrathecal oligoclonal immunoglobulin G in multiple sclerosis
  • Jan 1, 2020
  • Scripta Medica
  • Sanja Grgić + 6 more

Introduction/Aim: Detection of intrathecal oligoclonal bands of immunoglobulin G (OB IgG), in addition to diagnostic, has a predictive significance in multiple sclerosis (MS). The aim of the study was to determine the prognostic significance of OB IgG and to correlate the presence of OB IgG with the progression of disability in MS patients. Methods: A retrospective-prospective cohort study included 177 MS patients examined at the Centre for MS, Clinic of Neurology, University Clinical Centre of the Republic of Srpska. In all patients, demographic data, clinical parameters, Expanded Disability Status Scale (EDSS) score, isoelectric focusing (IEF) of cerebrospinal fluid (CSF), cyto-biochemical analysis of CSF, evoked potentials (EP) and magnetic resonance (MR) of the head were analysed. MS patients were divided in two groups: with and without intrathecal synthesis of oligoclonal IgG. According to the EDSS determined in both groups, the relation between the degree of functional disability and the presence of OB in the CSF and also with characteristics of the cyto-biochemical profile were analysed. Methods of descriptive and analytical statistics, analysis of variance, chi-square test, Bonferroni's post hoc test, correlation and regression analysis were used in the analysis of the results. Results: In the examined cohort of MS patients, the sensitivity of IEF was 96.6 %. There was a statistically significant association between the detectability of intrathecally synthesised IgG and EDSS score (p = 0.004) so that individuals who do not have intrathecally synthesised IgG had lower EDSS scores. MS patients with a CSF protein concentration &gt; 0.40 g/L were 2.45 times more likely to enter secondary progression and 2.51 times more likely to achieve EDSS 4.0. Conclusion: IEF is a very sensitive diagnostic and prognostic method for MS patients, which indicates a more benign course of MS in patients without oligoclonal bands in the CSF.

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  • Cite Count Icon 10
  • 10.1186/s12974-019-1574-5
Long-term use of interferon-\u03b2 in multiple sclerosis increases V\u03b41\u2212V\u03b42\u2212V\u03b39\u2212 \u03b3\u03b4 T cells that are associated with a better outcome
  • Sep 13, 2019
  • Journal of Neuroinflammation
  • Guzailiayi Maimaitijiang + 8 more

BackgroundWe previously reported that Vδ2+Vγ9+ γδ T cells were significantly decreased in multiple sclerosis (MS) patients without disease-modifying therapies (untreated MS) and were negatively correlated with Expanded Disability Status Scale (EDSS) scores, suggesting protective roles of Vδ2+Vγ9+ γδ T cells. Interferon-β (IFN-β) is one of the first-line disease-modifying drugs for MS. However, no previous studies have reported changes in γδ T cell subsets under IFN-β treatment. Therefore, we aimed to clarify the effects of the long-term usage of IFN-β on γδ T cell subsets in MS patients.MethodsComprehensive flow cytometric immunophenotyping was performed in 35 untreated MS and 21 MS patients on IFN-β for more than 2 years (IFN-β-treated MS) including eight super-responders fulfilling no evidence of disease activity criteria, and 44 healthy controls (HCs).ResultsThe percentages of Vδ2+Vγ9+ cells in γδ T cells were significantly lower in untreated and IFN-β-treated MS patients than in HCs. By contrast, the percentages of Vδ1−Vδ2−Vγ9− cells in γδ T cells were markedly higher in IFN-β-treated MS patients than in HCs and untreated MS patients (both p < 0.001). A significant negative correlation between the percentages of Vδ2+Vγ9+ cells in γδ T cells and EDSS scores was confirmed in untreated MS but not evident in IFN-β-treated MS. Moreover, class-switched memory B cells were decreased in IFN-β-treated MS compared with HCs (p < 0.001) and untreated MS patients (p = 0.006). Interestingly, the percentages of Vδ1−Vδ2−Vγ9− cells in γδ T cells were negatively correlated with class-switched memory B cell percentages in all MS patients (r = − 0.369, p = 0.005), and the percentages of Vδ1−Vδ2−Vγ9− cells in Vδ1−Vδ2− γδ T cells were negatively correlated with EDSS scores only in IFN-β super-responders (r = − 0.976, p < 0.001).ConclusionsThe present study suggests that long-term usage of IFN-β increases Vδ1−Vδ2−Vγ9− γδ T cells, which are associated with a better outcome, especially in IFN-β super-responders. Thus, increased Vδ1−Vδ2−Vγ9− cells together with decreased class-switched memory B cells may contribute to the suppression of disease activity in MS patients under IFN-β treatment.

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  • Cite Count Icon 7
  • 10.1080/1028415x.2021.1956253
The nutritional status of relapsing-remitting multiple sclerosis (RRMS) patients compared to that of healthy people: a Turkish hospital-based study
  • Jul 23, 2021
  • Nutritional Neuroscience
  • Tutku Atuk Kahraman + 3 more

Objective This study compares the nutritional status and physical activity levels of relapsing-remitting multiple sclerosis (RRMS) patients and healthy people. Method The study included 120 participants: 60 multiple sclerosis (MS) patients and 60 controls. RRMS diagnoses were made based on the 2017 McDonald criteria. The food intake frequency questionnaire was administered to the participants, their threeday food intake records were collected, their activity levels were determined, and anthropometric measurements were made. The differences between the groups were analyzed using the Mann–Whitney U test and Pearson's exact chi-squared test. Results The participants with MS (46.7%) had a significantly lower rate of shopping for their own food compared to the control group (68.3%) (p = 0.002). The MS group (3.3%) had a lower rate of intake of green leafy vegetables 5 times weekly or more frequently than the control group (20.0%) (p < 0.05); and the control group (35.0%) had a higher consumption rate of pastry more than 1 to 2 times monthly than the MS group (13.3%) (p < 0.05). The participants with MS had a higher intake of fiber, insoluble fiber, and omega 3 fatty acid than the control group (p < 0.05). Expanded Disability Status Scale (EDSS) scores indicates that a positive correlation was found between daily intake of fiber and insoluble fiber (p < 0.05). The patients with MS in the inactive group had a higher EDSS median [2.00(0.00 –5.00)] than the minimal active group [1.25(0.00 –4.00)] (p = 0.034). Conclusion With the increase in disability in MS patients, their physical activity levels decrease and it becomes difficult for them to shop on their own. In addition, the consumption frequency of green leafy vegetables, which take time to prepare and a source of fiber, is also decreasing. It has been shown that fiber intake decreases when the disability increase. Therefore, preventing the progression of disability in MS patients is very important in ensuring diversity in food consumption.

  • Abstract
  • 10.1182/blood-2023-181433
Autologous HSCT for Multiple Sclerosis Should be Done Early in the Course of the Disease
  • Nov 28, 2023
  • Blood
  • María De Lourdes Pastelín-Martínez + 12 more

Autologous HSCT for Multiple Sclerosis Should be Done Early in the Course of the Disease

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  • Cite Count Icon 12
  • 10.1016/j.msard.2020.102336
Metabolic syndrome components and disease disability in egyptian multiple sclerosis patients
  • Jul 3, 2020
  • Multiple Sclerosis and Related Disorders
  • Rasha M Fahmi + 3 more

Metabolic syndrome components and disease disability in egyptian multiple sclerosis patients

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  • Cite Count Icon 2
  • 10.7224/1537-2073-10.2.33
Expanded Disability Status Scale Calculator for Handheld Personal Digital Assistant: Reliability Study
  • Jan 1, 2008
  • International Journal of MS Care
  • Clyde E Markowitz + 5 more

Through a standard neurological examination, the Expanded Disability Status Scale (EDSS) score is traditionally determined by a pen-and-paper method. The objectives of this study were to compare the interrater/method reliability of EDSS scores obtained through the pen-and-paper method with those obtained with the EDSS Calculator, evaluate test-retest reliability of the EDSS Calculator, and examine the validity of EDSS Calculator scores through correlation with the Ambulation Index (AI). During a single office visit, 62 subjects with multiple sclerosis (MS) from six study centers had disability levels evaluated by separate raters using the EDSS calculator and pen-and-paper methods in random order. Seven days later, subjects returned for reevaluation with the EDSS Calculator; AI was also evaluated. Mean EDSS scores for the sample were 3.5 ± 2.2 with the calculator and 3.4 ± 2.0 (range 0–8) with the traditional method. Interrater reliability between scores with the two methods was high (κ = 0.84; confidence interval [CI], 0.74–0.94). Test-retest reliability with the calculator was also high (κ = 0.93; CI, 0.86–0.996). Correlation between disability scores from the EDSS Calculator and AI was 0.73 (P &amp;lt;.001). Relative to the pen-and paper method, the EDSS Calculator was found to be highly reliable and provide valid results when measuring disability in MS patients.

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  • Cite Count Icon 1
  • 10.4103/1110-1083.192658
Effects of vitamin D deficiency on the relapse, severity, and disability of multiple sclerosis
  • Jan 1, 2016
  • The Egyptian Journal of Neurology, Psychiatry and Neurosurgery
  • Ahmed Esmaela + 2 more

Background Multiple sclerosis (MS) is a long-standing inflammatory disease of the white matter and affects more than two million people worldwide. Upcoming evidence proposed that 25-hydroxy-vitamin D 3 (25HVD 3 ) deficiency could be one of the most crucial environmental elements for the pathogenesis of MS. Objective The aim of this study was to compare 25HVD 3 levels in MS patients and controls and to detect the association with relapse, severity, and disability in MS patients. Patients and methods Mansoura Neurology Department data sheet was collected and all patients were assessed using the Expanded Disability Status Scale (EDSS) at the onset. 25HVD 3 levels in the blood were evaluated for all patients and controls using the chemiluminescent immunoassay test. Results A total of 50 MS patients were included in this work and matched with 25 controls. There was a statistically significantly lower mean serum 25HVD 3 level in MS patients in comparison with the controls (20.5 ± 16.8 and 42.9 ± 17.9 ng/ml, respectively; P = 0.002). In addition, there was a statistically significantly lower level of 25HVD 3 (18.4 ± 17.7) in severe cases of MS (EDSS ≥ 6; P P P 3 deficiency ( Conclusion Our results showed that there is an inverse correlation between 25HVD 3 level and EDSS score. In addition, lower 25HVD 3 levels are associated with increased relapse risk in MS.

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  • Cite Count Icon 7
  • 10.17712/nsj.2020.3.20190093
Corpus callosum index correlates with brain volumetry and disability in multiple sclerosis patients.
  • Jul 1, 2020
  • Neurosciences
  • Stefanus E Sugijono + 4 more

Objectives:To analyze the correlation between corpus callosum index (CCI), brain volumetry, and disability in multiple sclerosis (MS) patients. The brain volumetry consists of the corpus callosum, cortical gray matter, subcortical gray matter, and white matter volumes.Methods:This was a retrospective cross-sectional study from October 2018 to February 2019 of 30 patients with MS aged 20 to 61 years old. Brain volumetry was performed using FreeSurfer© software. The CCI were measured manually using conventional best mid-sagittal T1W brain MRI. The anterior, posterior, and medium segments were measured and divided to its greatest anteroposterior diameter. Higher CCI values indicated greater corpus callosum volumes. Clinical evaluation was comprised of MS subtype, age of onset, relapse frequency and Expanded Disability Status Scale (EDSS).Results:Thirty MS patients with median of age 22 years were included. Relapsing-remitting (RRMS) subtype were 73.3%. Very significant correlations were shown between the CCI and corpus callosum volume (CCV) (r=0.79; p<0.0001) and cerebral white matter volume (r=0.81; p<0.0001). Significant correlations were shown between the CCI and cortical gray matter volume (r=0.64; p<0.0001) and subcortical gray matter volume (r=0.69; p<0.0001). The CCI was positively correlated with age of onset and inversely with EDSS. The CCV and CCI were smaller in secondary progressive MS (SPMS).Conclusion:The CCI is easy and fast to obtain in conventional MRI and significantly correlated with brain volumetry, age of onset and disability in MS patients.

  • Research Article
  • Cite Count Icon 15
  • 10.3109/00207454.2011.630543
Clinical Characteristics of Multiple Sclerosis in Kuwait: Data From the New MS Registry of Amiri Hospital
  • Nov 15, 2011
  • International Journal of Neuroscience
  • R Alroughani + 2 more

ABSTRACTObjectives: To study clinical characteristics of multiple sclerosis (MS) patients in Kuwait and to collect data on annual relapse rates and disability measures. Method: An MS Registry was created in Amiri Hospital. Demographic, clinical characteristics, and disability measures using Expanded Disability Status Scale (EDSS) score at last visit were collected. Results: Data from 218 patients formed the basis of the study cohort. Female to male ratio was 1.95. Mean age of onset of MS was 26.8 years. Seventy-eight percent had a relapsing–remitting course, 9.2% had secondary progressive course, and 2.8% had primary progressive course. The clinically isolated syndrome (CIS) group constituted 10.1%. The mean disease duration was 8 ± 7.2 years. Forty-five percent of patients had ≤5 years of disease duration, followed by 24.3% and 25.2% in the 5–10 and 10–20 years durations. Only 5.5% had MS for >20 years; 77.1% of patients had <1 relapse per year, while 22% had 1–2 relapses per year; 67.89% of patients had EDSS score <4, whereas 17.89% were found to have EDSS of ≥6. Summary: MS in Kuwait predominantly affects female. The mean age of onset and frequency of MS types are comparable to worldwide figures. The annual relapse rates and the EDSS scores were relatively low in our cohort.

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  • Cite Count Icon 6
  • 10.7759/cureus.25851
Clinical Profile and the Extent of Disability in Multiple Sclerosis Patients in Madinah, Saudi Arabia
  • Jun 11, 2022
  • Cureus
  • Esraa Q Alsaedi + 2 more

Objectives: The objective is to study the demographics and clinical characteristics of Saudi multiple sclerosis (MS) patients in Madinah, Saudi Arabia, and assess their extent of disability using the Expanded Disability Status Scale (EDSS).Methods: This hospital-based study intended to address the population of all MS-diagnosed patients registered between 2018 and 2021 in the Neurology Department of King Fahad Hospital in the Madinah region. Data were gathered from medical records and by interviewing participants in the Neurology Clinic. The chi-square test and linear and logistic regression were applied to draw inferences.Results: A total of 195 MS-diagnosed patients were included in the analysis. Of these, 72.3% were female. The mean age of the total sample was 34.9±9.2 years, and 7.7% reported a positive family history. Of all patients, 17.9% (n=35) had comorbidities. The mean age at diagnosis was 29.3±8.2 years. The majority (85.6%) were diagnosed with relapsing-remitting multiple sclerosis (RRMS); 77.9% had an EDSS score between 0.0 and 1.5, showing little or no disability. A statistical significance existed between EDSS and the current age of the patients (p=0.004), age at onset (p=0.007), type of MS (p=0.000), presence of muscle weakness (p=0.044), bladder or bowel difficulties at onset (p=0.043), and the duration of MS (p=0.000). Of the patients, 23.6% were not using disease-modifying therapy (DMT). The most commonly used drug was interferon beta 1-b.Conclusion: A lower EDSS was associated with younger age, diagnosis at a younger age, RRMS, duration less than five years, and lower body mass index (BMI). To increase the generalizability of findings, a national MS registry system and further prospective analytical epidemiological research studies are recommended.

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  • Cite Count Icon 63
  • 10.1007/s00415-011-6033-x
Prognostic value of multimodal evoked potentials in multiple sclerosis: the EP score
  • Apr 9, 2011
  • Journal of Neurology
  • Paolo Invernizzi + 5 more

Evoked potentials (EPs) have long been used as diagnostic tools in multiple sclerosis (MS), although their importance decreased as magnetic resonance imaging (MRI) became available. However, the prognostic value of EPs in MS has not been completely established. The aim of the study was to analyze the prognostic significance of EPs in a cohort of MS cases. From the Verona University Hospital MS Clinic database we retrospectively identified 80 MS patients who underwent a complete neurophysiological evaluation, including visual, brain stem, somatosensory and motor EPs and who were followed for at least 5 years after the study. EPs abnormalities were quantified through an index of global EPs alteration (EP score). The relationship between EP score and disability in terms of Expanded Disability Status Scale (EDSS) was analyzed by the Kaplan-Meier survival method and Spearman ρ correlation coefficient. ROC curves were used to determine the best EP score cut off to predict different EDSS endpoints. For each endpoint, sensitivity, specificity, positive and negative predictive value of EP score were calculated. We found a significant correlation (p < 0.001) between EP score and EDSS score at the time of neurophysiological study and at 1, 3 and 5 years of follow-up, particularly for motor and somatosensory EPs. Kaplan-Meier curves confirmed an increased risk of disability in those patients with EP score higher than the median value. EP score of 8 or 9 showed the highest sensitivity and specificity in predicting EDSS 4.0 and 6.0. EPs are reliable procedures to predict disability in MS patients. The correlation between EPs abnormalities and EDSS is higher than between conventional MRI and EDSS.

  • Abstract
  • 10.1016/j.jns.2013.07.1331
Disability improvement in the first case treated by Natalizumab in Libya
  • Sep 19, 2013
  • Journal of the Neurological Sciences
  • E.I Darmun + 1 more

Disability improvement in the first case treated by Natalizumab in Libya

  • Abstract
  • 10.1016/j.jns.2013.07.1332
Retrograde diagnosis of tumifactive multiple sclerosis
  • Sep 19, 2013
  • Journal of the Neurological Sciences
  • E Darmun + 1 more

Retrograde diagnosis of tumifactive multiple sclerosis

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