المؤلفون: Barbara Poletti, Edoardo Nicolò Aiello, Sofia Tagini, Federica Solca, Silvia Torre, Eleonora Colombo, Alessio Maranzano, Ruggero Bonetti, Francesco Schevegher, Claudia Morelli, Alberto Doretti, Federico Verde, Sergio Barbieri, Francesca Mameli, Alberto Priori, Roberta Ferrucci, Vincenzo Silani, Paolo Cherubini, Gabriella Pravettoni, Nicola Ticozzi

المصدر: Frontiers in Psychology, Vol 14 (2023)

مصطلحات موضوعية: counterfactual thinking, cognition, amyotrophic lateral sclerosis, frontotemporal degeneration, neuropsychology, dementia, Psychology, BF1-990

الوصف: ObjectivesThis study aimed at exploring (1) the motor and non-motor correlates of counterfactual thinking (CFT) abilities in non-demented amyotrophic lateral sclerosis (ALS) patients and (2) the ability of CFT measures to discriminate these patients from healthy controls (HCs) and patients with and without cognitive impairment.MethodsN = 110 ALS patients and N = 51 HCs were administered two CFT tasks, whose sum, resulting in a CFT Index (CFTI), was addressed as the outcome. Patients further underwent an in-depth cognitive, behavioral, and motor-functional evaluation. Correlational analyses were run to explore the correlates of the CFTI in patients. Logistic regressions were performed to test whether the CFTI could discriminate patients from HCs.ResultsThe CFTI was selectively associated (p ≤ 0.005) with fluency and memory subscales of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS), but not with other variables. CFTI scores discriminated patients from HCs (p < 0.001) with high accuracy (82%), but not patients with a normal vs. defective performance on the ECAS-Total.ConclusionCFT measures in non-demented ALS patients were associated with verbal fluency and memory functions, and they were also able to discriminate them from HCs.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fpsyg.2023.1281976/fullTest; https://doaj.org/toc/1664-1078Test

الوصول الحر: https://doaj.org/article/d1eb459721484e0e8eb0ce824bab77edTest

المؤلفون: Eleonora Colombo, Francesco Gentile, Alessio Maranzano, Alberto Doretti, Federico Verde, Marco Olivero, Delia Gagliardi, Matteo Faré, Megi Meneri, Barbara Poletti, Luca Maderna, Stefania Corti, Massimo Corbo, Claudia Morelli, Vincenzo Silani, Nicola Ticozzi

المصدر: Frontiers in Neurology, Vol 14 (2023)

مصطلحات موضوعية: amyotrophic lateral sclerosis, motor neuron disease, Penn upper motor neuron score, upper motor neuron involvement, transcranial magnetic stimulation, Neurology. Diseases of the nervous system, RC346-429

الوصف: ObjectivesIn amyotrophic lateral sclerosis (ALS) both upper (UMNs) and lower motor neurons (LMNs) are involved in the process of neurodegeneration, accounting for the great disease heterogeneity. We evaluated the associations of the burden of UMN impairment, assessed through the Penn Upper Motor Neuron Score (PUMNS), with demographic and clinical features of ALS patients to define the independent role of UMN involvement in generating disease heterogeneity, predicting disease progression and prognosis.MethodsWe collected the following clinical parameters on a cohort of 875 ALS patients: age and site of onset, survival, MRC scale, lower motor neuron score (LMNS), PUMNS, ALSFRS-R, change in ALSFRS-R over time (DFS), MITOS and King’s staging systems (KSS). Transcranial magnetic stimulation was performed on a subgroup of patients and central motor conduction time (CMCT) and cortical silent period (CSP) were calculated.ResultsWe observed that patients with an earlier age at onset and bulbar onset had higher PUMNS values. Higher values were also associated to lower ALSFRS-R and to higher DFS scores, as well as to higher MITOS and KSS, indicating that a greater UMN burden correlates with disease severity. Conversely, we did not appreciate any association between UMN involvement and survival or markers of LMN impairment. Moreover, PUMNS values showed a positive association with CMCT and a negative one with CSP values.InterpretationOur results suggest that the burden of UMN pathology, assessed through PUMNS, has an important independent role in defining clinical characteristics, functional disability, disease progression and prognosis in ALS patients. We also support the role of TMS in defining severity of UMN involvement.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fneur.2023.1249429/fullTest; https://doaj.org/toc/1664-2295Test

الوصول الحر: https://doaj.org/article/59b23ad3152a44948653a44223dafc5eTest

المؤلفون: Federico Verde, Ilaria Milone, Alessio Maranzano, Eleonora Colombo, Silvia Torre, Federica Solca, Alberto Doretti, Francesco Gentile, Arianna Manini, Ruggero Bonetti, Silvia Peverelli, Stefano Messina, Luca Maderna, Claudia Morelli, Barbara Poletti, Antonia Ratti, Vincenzo Silani, Nicola Ticozzi

المصدر: Annals of Clinical and Translational Neurology, Vol 10, Iss 1, Pp 118-129 (2023)

مصطلحات موضوعية: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429

الوصف: Abstract Objective To compare serum levels of the astrocyte biomarker glial fibrillary acidic protein (GFAP) in patients with amyotrophic lateral sclerosis (ALS) and neurologically healthy controls and to analyze the relations between serum GFAP (sGFAP) and phenotype in ALS. Methods We studied 114 ALS patients and 38 controls. sGFAP was quantified with single molecule array (Simoa) technology. Results In both ALS patients and controls, sGFAP moderately correlated with age. ALS patients had higher sGFAP levels compared to controls, but this yielded a weak discriminative performance (AUC = 0.6198). In ALS, sGFAP was not associated with most of the motor phenotypic features, including site of onset, functional status, disease progression rate, disease stage, and indices of upper (UMN) and lower motor neuron (LMN) impairment. However, sGFAP negatively correlated with cognitive scores regarding ALS‐nonspecific functions, particularly memory (r = −0.2082) and tended to be higher in ALS patients with eye movement abnormalities (p = 0.0628). sGFAP also correlated with polysomnographic indices of oxygen desaturation (ODI; r = 0.2639) and apnea‐hypopnea (AHI; r = 0.2858). In a multivariate analysis, sGFAP was negatively associated with survival (HR = 1.005). Relevantly, we found a negative correlation between sGFAP and estimated glomerular filtration rate (eGFR; r = −0.3500). Interpretation Our work provides neurochemical evidence of astrocyte involvement in ALS pathophysiology and particularly in the development of extra‐motor manifestations (namely, cognitive – memory – impairment) and respiratory dysfunction. The negative correlation between sGFAP and eGFR has practical relevance and should not be disregarded in future investigations.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2328-9503Test

الوصول الحر: https://doaj.org/article/e1afc3f985cc440dbee2028851a2a72dTest

المؤلفون: Edoardo Nicolò Aiello, Federica Solca, Silvia Torre, Valerio Patisso, Alberto De Lorenzo, Mauro Treddenti, Eleonora Colombo, Alessio Maranzano, Claudia Morelli, Alberto Doretti, Federico Verde, Vincenzo Silani, Nicola Ticozzi, Barbara Poletti

المصدر: Frontiers in Aging Neuroscience, Vol 15 (2023)

مصطلحات موضوعية: bulbar, Frontotemporal Degeneration, cognition, neuropsychology, amyotrophic lateral sclerosis, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

الوصف: BackgroundThis study aimed at clarifying the role of bulbar involvement (BI) as a risk factor for cognitive impairment (CI) in non-demented amyotrophic lateral sclerosis (ALS) patients.MethodsData on N = 347 patients were retrospectively collected. Cognition was assessed via the Edinburgh Cognitive and Behavioral ALS Screen (ECAS). On the basis of clinical records and ALS Functional Rating Scale-Revised (ALSFRS-R) scores, BI was characterized as follows: (1) BI at onset—from medical history; (2) BI at testing (an ALSFRS-R-Bulbar score ≤11); (3) dysarthria (a score ≤3 on item 1 of the ALSFRS-R); (4) severity of BI (the total score on the ALSFRS-R-Bulbar); and (5) progression rate of BI (computed as 12-ALSFRS-R-Bulbar/disease duration in months). Logistic regressions were run to predict a below- vs. above-cutoff performance on each ECAS measure based on BI-related features while accounting for sex, disease duration, severity and progression rate of respiratory and spinal involvement and ECAS response modality.ResultsNo predictors yielded significance either on the ECAS-Total and -ALS-non-specific or on ECAS-Language/-Fluency or -Visuospatial subscales. BI at testing predicted a higher probability of an abnormal performance on the ECAS-ALS-specific (p = 0.035) and ECAS-Executive Functioning (p = 0.018). Lower ALSFRS-R-Bulbar scores were associated with a defective performance on the ECAS-Memory (p = 0.025). No other BI-related features affected other ECAS performances.DiscussionIn ALS, the occurrence of BI itself, while neither its specific features nor its presence at onset, might selectively represent a risk factor for executive impairment, whilst its severity might be associated with memory deficits.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fnagi.2023.1217080/fullTest; https://doaj.org/toc/1663-4365Test

الوصول الحر: https://doaj.org/article/aa3ff696ea5443739329587c54b78f1fTest

المؤلفون: Federico Verde, Ilaria Milone, Eleonora Colombo, Alessio Maranzano, Federica Solca, Silvia Torre, Alberto Doretti, Francesco Gentile, Arianna Manini, Ruggero Bonetti, Silvia Peverelli, Stefano Messina, Luca Maderna, Claudia Morelli, Barbara Poletti, Antonia Ratti, Vincenzo Silani, Nicola Ticozzi

المصدر: Frontiers in Aging Neuroscience, Vol 15 (2023)

مصطلحات موضوعية: amyotrophic lateral sclerosis (ALS), motor neuron disease (MND), neurofilament light chain (NFL), axon, biomarker, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

الوصف: ObjectiveTo investigate the relationship between serum levels of the neuroaxonal degeneration biomarker neurofilament light chain (NFL) and phenotype in ALS.Materials and methodsSerum NFL (sNFL) concentration was quantified in 209 ALS patients and 46 neurologically healthy controls (NHCs).ResultssNFL was clearly increased in ALS patients and discriminated them from NHCs with AUC = 0.9694. Among ALS patients, females had higher sNFL levels, especially in case of bulbar onset. sNFL was more increased in phenotypes with both upper (UMN) and lower motor neuron (LMN) signs, and particularly in those with UMN predominance, compared to LMN forms. At the same time, primary lateral sclerosis (PLS) had significantly lower levels compared to UMN-predominant ALS (AUC = 0.7667). sNFL correlated negatively with disease duration at sampling and ALSFRS-R score, positively with disease progression rate, differed among King’s stages, and was negatively associated with survival. It also correlated with clinical/neurophysiological indices of UMN and LMN dysfunction (Penn UMN Score, LMN score, MRC composite score, active spinal denervation score). On the contrary, sNFL was not associated with cognitive deficits nor with respiratory parameters. Notably, we found a negative correlation between sNFL and estimated glomerular filtration rate (eGFR).InterpretationWe confirm that ALS is characterized by increased sNFL levels, whose main determinant is the rate of degeneration of both UMNs and LMNs. sNFL is a biomarker of only motor, not of extra-motor, disease. The negative correlation with kidney function might reflect varying renal clearance of the molecule and deserves further investigation before introducing sNFL measurement as routine test in clinical care of ALS patients.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fnagi.2023.1132808/fullTest; https://doaj.org/toc/1663-4365Test

الوصول الحر: https://doaj.org/article/d1ff32eb10ce42839bc554c47893310cTest

المؤلفون: Arianna Manini, Valeria Casiraghi, Alberto Brusati, Alessio Maranzano, Francesco Gentile, Eleonora Colombo, Ruggero Bonetti, Silvia Peverelli, Sabrina Invernizzi, Davide Gentilini, Stefano Messina, Federico Verde, Barbara Poletti, Isabella Fogh, Claudia Morelli, Vincenzo Silani, Antonia Ratti, Nicola Ticozzi

المصدر: Frontiers in Aging Neuroscience, Vol 15 (2023)

مصطلحات موضوعية: amyotrophic lateral sclerosis, UNC13A, alleles, genotype, motor neurons, behavioral symptoms, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

الوصف: BackgroundThe UNC13A gene is an established susceptibility locus for amyotrophic lateral sclerosis (ALS) and a determinant of shorter survival after disease onset, with up to 33.0 months difference in life expectancy for carriers of the rs12608932 risk genotype. However, its overall effect on other clinical features and ALS phenotypic variability is controversial.MethodsGenotype data of the UNC13A rs12608932 SNP (A–major allele; C–minor allele) was obtained from a cohort of 972 ALS patients. Demographic and clinical variables were collected, including cognitive and behavioral profiles, evaluated through the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) – Italian version and the Frontal Behavioral Inventory (FBI); upper and lower motor neuron involvement, assessed by the Penn Upper Motor Neuron Score (PUMNS) and the Lower Motor Neuron Score (LMNS)/Medical Research Council (MRC) scores, respectively; the ALS Functional Rating Scale Revised (ALSFRS-R) score at evaluation and progression rate; age and site of onset; survival. The comparison between the three rs12608932 genotypes (AA, AC, and CC) was performed using the additive, dominant, and recessive genetic models.ResultsThe rs12608932 minor allele frequency was 0.31 in our ALS cohort, in comparison to 0.33–0.41 reported in other Caucasian ALS populations. Carriers of at least one minor C allele (AC + CC genotypes) had a shorter median survival than patients with the wild-type AA genotype (−11.7 months, p = 0.013), even after adjusting for age and site of onset, C9orf72 mutational status and gender. Patients harboring at least one major A allele (AA + AC genotypes) and particularly those with the wild-type AA genotype showed a significantly higher PUMNS compared to CC carriers (p = 0.015 and padj = 0.037, respectively), thus indicating a more severe upper motor neuron involvement. Our analysis did not detect significant associations with all the other clinical parameters considered.ConclusionOverall, our findings confirm the role of UNC13A as a determinant of survival in ALS patients and show the association of this locus also with upper motor neuron involvement.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fnagi.2023.1067954/fullTest; https://doaj.org/toc/1663-4365Test

الوصول الحر: https://doaj.org/article/ab3bde1bf5394265b98be74e3d334377Test

المؤلفون: Edoardo Nicolò Aiello, Federica Solca, Lucia Catherine Greco, Antonino La Tona, Silvia Torre, Laura Carelli, Claudia Morelli, Alberto Doretti, Eleonora Colombo, Stefano Messina, Debora Pain, Alice Radici, Andrea Lizio, Jacopo Casiraghi, Federica Cerri, Agostino Brugnera, Angelo Compare, Susan Woolley, Jennifer Murphy, Lucio Tremolizzo, Ildebrando Appollonio, Federico Verde, Valeria Ada Sansone, Christian Lunetta, Vincenzo Silani, Nicola Ticozzi, Barbara Poletti

المصدر: Frontiers in Psychology, Vol 13 (2023)

مصطلحات موضوعية: ALS Cognitive Behavioral Screen, amyotrophic lateral sclerosis, behavior, frontotemporal degeneration, dysexecutive, Psychology, BF1-990

الوصف: BackgroundThe present investigation aimed at testing the psychometrics and diagnostics of the Italian version of the Caregiver Behavioral Questionnaire (CBQ) from the ALS Cognitive Behavioral Screen (ALS-CBS™), as well as its case–control discrimination, in a cohort of non-demented patients with ALS.MethodsThe caregivers of N = 265 non-demented patients with ALS and N = 99 healthy controls (HCs) were administered the CBQ and the Edinburgh Cognitive and Behavioural ALS Screen-Carer Interview (ECAS-CI). For N = 98 patients, an in-depth behavioural/psychopathological assessment via the Frontal Behavioural Inventory (FBI), the Dimensional Apathy Scale (DAS), the State and Trait Anxiety Inventory-Form Y (STAI-Y), and the Beck Depression Inventory (BDI) was also available. Factorial and construct validity, internal reliability, and diagnostics against an abnormal ECAS-CI score were tested in patients. Case–control discrimination was explored through logistic regression.ResultsThe CBQ was internally reliable (McDonald’s ω = 0.90) and underpinned by a simple, unidimensional structure; it converged with ECAS-CI, FBI, and DAS scores and diverged from STAI-Y and BDI ones. A cutoff of ≤ 33 accurately detected abnormal ECAS-CI scores (AUC = 0.85), yielding optimal error- and information-based diagnostics. The CBQ was independent of demographic and disease-related variables and discriminated patients from HCs (p < 0.001).DiscussionThe Italian version of the CBQ from the ALS-CBS™ is a valid, reliable, diagnostically sound, and feasible screener for detecting frontotemporal-like behavioural changes in non-demented patients with ALS. Its adoption is thus recommended within clinical practice and research in the view of providing preliminary information on whether the administration of more extensive behavioural instruments is needed.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fpsyg.2022.1107001/fullTest; https://doaj.org/toc/1664-1078Test

الوصول الحر: https://doaj.org/article/9b8f0b2f6bc24894b4e4d0c114756194Test

المؤلفون: Jacopo Pasquini, Francesca Trogu, Claudia Morelli, Barbara Poletti, Floriano Girotti, Silvia Peverelli, Alberto Brusati, Antonia Ratti, Andrea Ciammola, Vincenzo Silani, Nicola Ticozzi

المصدر: Frontiers in Aging Neuroscience, Vol 14 (2022)

مصطلحات موضوعية: motor neuron disease (MND), parkinsonism, amyotrophic lateral sclerosis, primary lateral sclerosis (PLS), progressive supranuclear palsy, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

الوصف: BackgroundParkinsonian syndromes may rarely occur in motor neuron disease (MND). However, previous studies are heterogeneous and mostly case reports or small case series. Therefore, we aimed to identify and characterize patients with concurrent parkinsonian syndromes extracted from a cohort of 1,042 consecutive cases diagnosed with MND at a tertiary Italian Center.MethodsDiagnosis of Parkinson's disease (PD), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) was made according to current criteria. Clinical characterization included: upper and lower motor neuron disease features, typical and atypical parkinsonian features, oculomotor disorders, cognitive testing, MRI features, and, when available molecular neuroimaging. Genetic testing was carried out for major MND and PD-associated genes.ResultsParkinsonian syndromes were diagnosed in 18/1042 (1.7%) of MND patients (7 PD, 6 PSP, 3 CBS, 2 other parkinsonisms). Based on phenotype, patients could be categorized into amyotrophic lateral sclerosis (ALS)-parkinsonism and primary lateral sclerosis (PLS)-parkinsonism clusters. Across the whole database, parkinsonism was significantly more common in PLS than in other MND phenotypes (12.1 vs. 1.1%, p = 5.0 × 10−10). MND patients with parkinsonian features had older age of onset, higher frequency of oculomotor disorders, cognitive impairment, and family history of parkinsonism or dementia. Two patients showed pathogenic mutations in TARDBP and C9orf72 genes.ConclusionSpecific patterns in MND-parkinsonism were observed, with PLS patients often showing atypical parkinsonian syndromes and ALS patients more frequently showing typical PD. Systematic clinical, genetic, and neuropathologic characterization may provide a better understanding of these phenotypes.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fnagi.2022.917706/fullTest; https://doaj.org/toc/1663-4365Test

الوصول الحر: https://doaj.org/article/fa7507a65a6849e0a1c54ec94b5e07c8Test

المؤلفون: Sebastiano Cicco, Marialuisa Sveva Marozzi, Carmen Alessandra Palumbo, Elisabetta Sturdà, Antonio Fusillo, Flavio Scarilli, Federica Albanese, Claudia Morelli, Davide Fiore Bavaro, Lucia Diella, Annalisa Saracino, Fabrizio Pappagallo, Antonio Giovanni Solimando, Gianfranco Lauletta, Roberto Ria, Angelo Vacca

المصدر: Medicina, Vol 59, Iss 2, p 203 (2023)

مصطلحات موضوعية: Bamlanivimab, Etesevimab, COVID-19, lung ultrasound, Medicine (General), R5-920

الوصف: Background and Objectives: COVID-19 induces massive systemic inflammation. Researchers have spent much time and effort finding an excellent and rapid image tool to evaluate COVID-19 patients. Since the pandemic’s beginning, lung ultrasound (LUS) has been identified for this purpose. Monoclonal antibodies (mAb) were used to treat mild patients and prevent respiratory disease worsening. Materials and Methods: We evaluated 15 Caucasian patients with mild COVID-19 who did not require home oxygen, treated with Bamlanivimab and Etesevimab (Group 1). A molecular nose–throat swab test confirmed the diagnosis. All were office patients, and nobody was affected by respiratory failure. They were admitted to receive the single-day infusion of mAb treatment in agreement with the Italian Drug Agency (AIFA) rules for approval. LUS was performed before the drug administration (T0) and after three months (T1). We compared LUS at T1 in other outpatients who came for follow-up and were overlapping at the time of diagnosis for admittance criteria to receive mAb (Group 2). Results: Our COVID-19 outpatients reported no hospitalization in a follow-up visit after recovery. All patients became SARS-CoV-2 negative within one month since T0. LUS score at T0 was 8.23 ± 6.46. At T1 we found a significant decrease in Group 1 LUS score (5.18 ± 4.74; p < 0.05). We also found a significant decrease in the LUS score of Group 1 T1 compared to Group2 T1 (5.18 ± 4.74 vs 7.82 ± 5.21; p < 0.05). Conclusion: Early treatment of the SARS-CoV-2 virus effectively achieves a better recovery from disease and reduces lung involvement after three months as evaluated with LUS. Despite extrapolation to the general population may be done with caution, based on our data this ultrasound method is also effective for evaluating and following lung involvement in COVID-19 patients.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1648-9144/59/2/203Test; https://doaj.org/toc/1010-660XTest; https://doaj.org/toc/1648-9144Test

الوصول الحر: https://doaj.org/article/94101ceff61847b483b2e1cdf508e93fTest

المؤلفون: Arianna Manini, Antonia Ratti, Alberto Brusati, Alessio Maranzano, Isabella Fogh, Silvia Peverelli, Stefano Messina, Davide Gentilini, Federico Verde, Barbara Poletti, Claudia Morelli, Vincenzo Silani, Nicola Ticozzi

المصدر: International Journal of Molecular Sciences, Vol 23, Iss 16, p 9276 (2022)

مصطلحات موضوعية: amyotrophic lateral sclerosis, frontotemporal lobar degeneration, TMEM106B, alleles, cognition, motor neurons, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: The transmembrane protein 106B (TMEM106B) gene is a susceptibility factor and disease modifier of frontotemporal dementia, but few studies have investigated its role in amyotrophic lateral sclerosis. The aim of this work was to assess the impact of the TMEM106B rs1990622 (A–major risk allele; G–minor allele) on phenotypic variability of 865 patients with amyotrophic lateral sclerosis. Demographic and clinical features were compared according to genotypes by additive, dominant, and recessive genetic models. Bulbar onset was overrepresented among carriers of the AA risk genotype, together with enhanced upper motor neuron involvement and poorer functional status in patients harboring at least one major risk allele (A). In a subset of 195 patients, we found that the homozygotes for the minor allele (GG) showed lower scores at the Edinburgh Cognitive and Behavioral Amyotrophic Lateral Sclerosis Screen, indicating a more severe cognitive impairment, mainly involving the amyotrophic lateral sclerosis-specific cognitive functions and memory. Moreover, lower motor neuron burden predominated among patients with at least one minor allele (G). Overall, we found that TMEM106B is a disease modifier of amyotrophic lateral sclerosis, whose phenotypic effects encompass both sites of onset and functional status (major risk allele), motor functions (both major risk and minor alleles), and cognition (minor allele).

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/23/16/9276Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/f58d83db78364e5cac94ce82ed956f03Test