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Robert J. Robbins is a biologist, an educator, a science administrator, a publisher, an information technologist, and an IT leader and manager who specializes in advancing biomedical knowledge and supporting education through the application of information technology. More About: RJR | OUR TEAM | OUR SERVICES | THIS WEBSITE
RJR: Recommended Bibliography 11 Dec 2025 at 01:34 Created:
Amyotrophic Lateral Sclerosis
Amyotrophic lateral sclerosis (ALS), also known as motor neurone disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most common form of the motor neuron diseases. Early symptoms of ALS include stiff muscles, muscle twitches, and gradual increasing weakness and muscle wasting. Limb-onset ALS begins with weakness in the arms or legs, while bulbar-onset ALS begins with difficulty speaking or swallowing. Around half of people with ALS develop at least mild difficulties with thinking and behavior, and about 15% develop frontotemporal dementia. Motor neuron loss continues until the ability to eat, speak, move, and finally the ability to breathe is lost. Most cases of ALS (about 90% to 95%) have no known cause, and are known as sporadic ALS. However, both genetic and environmental factors are believed to be involved. The remaining 5% to 10% of cases have a genetic cause, often linked to a history of the disease in the family, and these are known as genetic ALS. About half of these genetic cases are due to disease-causing variants in one of two specific genes. The diagnosis is based on a person's signs and symptoms, with testing conducted to rule out other potential causes.
Created with PubMed® Query: ( ALS*[TIAB] OR "amyotrophic lateral sclerosis"[TIAB] ) NOT pmcbook NOT ispreviousversion
Citations The Papers (from PubMed®)
RevDate: 2025-12-10
Ubiquitin Proteasome System Components, RAD23A and USP13, Modulate TDP-43 Solubility and Neuronal Toxicity.
The Journal of neuroscience : the official journal of the Society for Neuroscience pii:JNEUROSCI.0906-25.2025 [Epub ahead of print].
At autopsy, >95% of ALS cases display a redistribution of the essential RNA binding protein TDP-43 from the nucleus into cytoplasmic aggregates. The mislocalization and aggregation of TDP-43 is believed to be a key pathological driver in ALS. Due to its vital role in basic cellular mechanisms, direct depletion of TDP-43 is unlikely to lead to a promising therapy. Therefore, we have explored the utility of identifying genes that modify its mislocalization or aggregation. We have previously shown that loss of rad-23 improves locomotor deficits in TDP-43 C. elegans models of disease and increases the degradation rate of TDP-43 in cellular models. To understand the mechanism through which these protective effects occur, we generated an inducible mutant TDP-43 HEK293 cell line. We find that knockdown of RAD23A reduces insoluble TDP-43 levels in this model and primary rat cortical neurons expressing human TDP-43[A315T] Utilizing a discovery-based proteomics approach, we then explored how loss of RAD23A remodels the proteome. Through this proteomic screen, we identified USP13, a deubiquitinase, as a new potent modifier of TDP-43 induced aggregation and cytotoxicity. We find that knockdown of USP13 reduces the abundance of sarkosyl insoluble mTDP-43 in both our HEK293 model and primary rat neurons, reduces cell death in primary rat motor neurons, and improves locomotor deficits in C. elegans ALS models.Significance Statement Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease (NDD) with no effective therapies. The mislocalization and aggregation of TAR DNA binding protein 43 (TDP-43) is a key pathological marker of ALS and other NDDs. Due to its vital functions, targeted therapeutic reduction of TDP-43 could be problematic. Here, we have explored the utility of targeting modifier genes. We find that knockdown of two members of the ubiquitin proteasome system, RAD23A and USP13, enhance TDP-43 solubility and decrease TDP-43 induced neurotoxicity.
Additional Links: PMID-41371952
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@article {pmid41371952,
year = {2025},
author = {Dalton, C and Mojsilovic-Petrovic, J and Safren, N and Snoznik, C and Gebis, KK and Wang, YZ and Sutter, AB and Lamitina, T and Savas, JN and Kalb, RG},
title = {Ubiquitin Proteasome System Components, RAD23A and USP13, Modulate TDP-43 Solubility and Neuronal Toxicity.},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1523/JNEUROSCI.0906-25.2025},
pmid = {41371952},
issn = {1529-2401},
abstract = {At autopsy, >95% of ALS cases display a redistribution of the essential RNA binding protein TDP-43 from the nucleus into cytoplasmic aggregates. The mislocalization and aggregation of TDP-43 is believed to be a key pathological driver in ALS. Due to its vital role in basic cellular mechanisms, direct depletion of TDP-43 is unlikely to lead to a promising therapy. Therefore, we have explored the utility of identifying genes that modify its mislocalization or aggregation. We have previously shown that loss of rad-23 improves locomotor deficits in TDP-43 C. elegans models of disease and increases the degradation rate of TDP-43 in cellular models. To understand the mechanism through which these protective effects occur, we generated an inducible mutant TDP-43 HEK293 cell line. We find that knockdown of RAD23A reduces insoluble TDP-43 levels in this model and primary rat cortical neurons expressing human TDP-43[A315T] Utilizing a discovery-based proteomics approach, we then explored how loss of RAD23A remodels the proteome. Through this proteomic screen, we identified USP13, a deubiquitinase, as a new potent modifier of TDP-43 induced aggregation and cytotoxicity. We find that knockdown of USP13 reduces the abundance of sarkosyl insoluble mTDP-43 in both our HEK293 model and primary rat neurons, reduces cell death in primary rat motor neurons, and improves locomotor deficits in C. elegans ALS models.Significance Statement Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease (NDD) with no effective therapies. The mislocalization and aggregation of TAR DNA binding protein 43 (TDP-43) is a key pathological marker of ALS and other NDDs. Due to its vital functions, targeted therapeutic reduction of TDP-43 could be problematic. Here, we have explored the utility of targeting modifier genes. We find that knockdown of two members of the ubiquitin proteasome system, RAD23A and USP13, enhance TDP-43 solubility and decrease TDP-43 induced neurotoxicity.},
}
RevDate: 2025-12-10
Response to Huang et al's ''Real-world efficacy of ritlecitinib in treating alopecia areata across various anatomical sites: Potential rapid response predictors".
Additional Links: PMID-41371413
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@article {pmid41371413,
year = {2025},
author = {Spindler, A and Maas, D and Zappi, I and Senna, MM and Shapiro, J and Lo Sicco, KI},
title = {Response to Huang et al's ''Real-world efficacy of ritlecitinib in treating alopecia areata across various anatomical sites: Potential rapid response predictors".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.10.161},
pmid = {41371413},
issn = {1097-6787},
}
RevDate: 2025-12-10
Nocturnal hypoxemia mediates age-related sleep fragmentation in amyotrophic lateral sclerosis: a polysomnographic case-control study.
Acta neurologica Belgica [Epub ahead of print].
OBJECTIVE: To evaluate sleep architecture disruptions in amyotrophic lateral sclerosis (ALS) using polysomnography (PSG) and identify clinical/demographic correlates for targeted interventions.
METHODS: Forty definite/probable ALS patients (revised El Escorial criteria) without primary sleep disorders and 40 age/sex/BMI-matched controls underwent full polysomnography (PSG). Sleep parameters (total sleep time [TST], sleep efficiency [SE], wake after sleep onset [WASO], N1-N3, rapid eye movement [REM] sleep), respiratory indices (AHI, minimum peripheral oxygen saturation (min SpO₂), SpO₂ range/coefficient of variation [CV]), and clinical metrics (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised [ALSFRS-R], Hospital Anxiety and Depression Scale [HADS]) were compared. Multivariate regression identified independent sleep predictors, and mediation analysis quantified min SpO₂'s role in age-sleep fragmentation relationships.
RESULTS: ALS patients showed significantly reduced TST (371.54 ± 67.62 vs. 495.13 ± 45.69 min, p = 0.004), SE (69.95 ± 13.79 vs. 85.10 ± 7.03%, p = 0.009), N2 sleep (127.33 ± 56.75 vs. 204.28 ± 67.16 min, p = 0.013), N3 sleep (61.70 ± 33.67 vs. 91.90 ± 44.06 min, p = 0.021), and REM sleep (66.09 ± 35.85 vs. 84.66 ± 37.65 min, p = 0.012) alongside elevated WASO (131.70 ± 78.82 vs. 64.26 ± 44.18 min, p = 0.015). Nocturnal oxygenation was impaired (min SpO₂: 89.3 ± 3.1% vs. 93.7 ± 2.4%, p < 0.001; SpO₂ CV: 3.7 ± 1.5% vs. 1.8 ± 0.9%, p < 0.001), though AHI and REM AHI were comparable (AHI: p = 0.087; REM AHI: p = 0.134). Age (β = -0.28, p = 0.02) and min SpO₂ (β = 0.31, p = 0.01) independently predicted TST. Mediation analysis confirmed min SpO₂ partially explains age-related TST reduction (indirect effect: -0.14, 95% CI: -0.28 to - 0.03; accounting for 43.8% of the total effect).
CONCLUSION: Our data confirm profound sleep architecture disruption and nocturnal hypoxemia in ALS independent of primary sleep disorders. Critically, we establish min SpO₂ as a partial mediator of age-related sleep fragmentation, suggesting that early management of hypoxemia may improve sleep quality. Larger prospective studies validating these mechanisms and their impact on disease progression are warranted.
Additional Links: PMID-41370023
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@article {pmid41370023,
year = {2025},
author = {Ding, W and Guo, J and Lu, Y and Li, X},
title = {Nocturnal hypoxemia mediates age-related sleep fragmentation in amyotrophic lateral sclerosis: a polysomnographic case-control study.},
journal = {Acta neurologica Belgica},
volume = {},
number = {},
pages = {},
pmid = {41370023},
issn = {2240-2993},
abstract = {OBJECTIVE: To evaluate sleep architecture disruptions in amyotrophic lateral sclerosis (ALS) using polysomnography (PSG) and identify clinical/demographic correlates for targeted interventions.
METHODS: Forty definite/probable ALS patients (revised El Escorial criteria) without primary sleep disorders and 40 age/sex/BMI-matched controls underwent full polysomnography (PSG). Sleep parameters (total sleep time [TST], sleep efficiency [SE], wake after sleep onset [WASO], N1-N3, rapid eye movement [REM] sleep), respiratory indices (AHI, minimum peripheral oxygen saturation (min SpO₂), SpO₂ range/coefficient of variation [CV]), and clinical metrics (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised [ALSFRS-R], Hospital Anxiety and Depression Scale [HADS]) were compared. Multivariate regression identified independent sleep predictors, and mediation analysis quantified min SpO₂'s role in age-sleep fragmentation relationships.
RESULTS: ALS patients showed significantly reduced TST (371.54 ± 67.62 vs. 495.13 ± 45.69 min, p = 0.004), SE (69.95 ± 13.79 vs. 85.10 ± 7.03%, p = 0.009), N2 sleep (127.33 ± 56.75 vs. 204.28 ± 67.16 min, p = 0.013), N3 sleep (61.70 ± 33.67 vs. 91.90 ± 44.06 min, p = 0.021), and REM sleep (66.09 ± 35.85 vs. 84.66 ± 37.65 min, p = 0.012) alongside elevated WASO (131.70 ± 78.82 vs. 64.26 ± 44.18 min, p = 0.015). Nocturnal oxygenation was impaired (min SpO₂: 89.3 ± 3.1% vs. 93.7 ± 2.4%, p < 0.001; SpO₂ CV: 3.7 ± 1.5% vs. 1.8 ± 0.9%, p < 0.001), though AHI and REM AHI were comparable (AHI: p = 0.087; REM AHI: p = 0.134). Age (β = -0.28, p = 0.02) and min SpO₂ (β = 0.31, p = 0.01) independently predicted TST. Mediation analysis confirmed min SpO₂ partially explains age-related TST reduction (indirect effect: -0.14, 95% CI: -0.28 to - 0.03; accounting for 43.8% of the total effect).
CONCLUSION: Our data confirm profound sleep architecture disruption and nocturnal hypoxemia in ALS independent of primary sleep disorders. Critically, we establish min SpO₂ as a partial mediator of age-related sleep fragmentation, suggesting that early management of hypoxemia may improve sleep quality. Larger prospective studies validating these mechanisms and their impact on disease progression are warranted.},
}
RevDate: 2025-12-10
Amyotrophic lateral sclerosis in Colombia: a population-based study of incidence and socioeconomic determinants.
Amyotrophic lateral sclerosis & frontotemporal degeneration [Epub ahead of print].
Background and Objectives: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder with variable global incidence. In Latin America, limited population-level data hinder accurate burden estimation and public health planning. This study estimated ALS incidence in Colombia from 1984 to 2024, analyzing regional distribution patterns and the demographic and socioeconomic profiles of affected individuals. Methods: This cross-sectional, population-based study analyzed 2185 clinically confirmed ALS cases reported to the Colombian National Institute of Health. Diagnoses were established using El Escorial or Gold Coast criteria. Annual and cumulative incidence rates were estimated using national population data. Demographic, geographic, and socioeconomic variables were classified under international standards, and all statistical analyses were performed using Python (version 3.12). Results: A total of 2185 ALS cases diagnosed between 1984 and 2024 were included. For the most recent decade (2015-2024), the national cumulative incidence was 41.46 per million inhabitants, with a steady increase in annual incidence. Bogotá and Caldas showed the highest cumulative incidence, whereas Chocó and Casanare reported the lowest. The mean age at diagnosis was 59.9 years, with a slight male predominance (male-to-female ratio 1.11:1). Socioeconomic disparities were evident: 18.0% of patients had no formal education, and over 40% were economically inactive at diagnosis. Conclusions: ALS incidence in Colombia is lower than that reported in high-income regions, but shows pronounced geographic and socioeconomic heterogeneity. These findings underscore the need to strengthen diagnostic capacity, improve equitable access to neurology services, and advance research on environmental and genetic determinants of ALS in Latin America.
Additional Links: PMID-41369024
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@article {pmid41369024,
year = {2025},
author = {Correa-Arrieta, C and Castellar-Leones, S and Ruiz-Ospina, E and Diaz-Ruiz, J and Sanchez-Peñarete, D and Rodriguez-Cruz, W and Bravo-Espejo, J and Uriza-Prias, DM and Ortiz-Corredor, F},
title = {Amyotrophic lateral sclerosis in Colombia: a population-based study of incidence and socioeconomic determinants.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/21678421.2025.2597944},
pmid = {41369024},
issn = {2167-9223},
abstract = {Background and Objectives: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder with variable global incidence. In Latin America, limited population-level data hinder accurate burden estimation and public health planning. This study estimated ALS incidence in Colombia from 1984 to 2024, analyzing regional distribution patterns and the demographic and socioeconomic profiles of affected individuals. Methods: This cross-sectional, population-based study analyzed 2185 clinically confirmed ALS cases reported to the Colombian National Institute of Health. Diagnoses were established using El Escorial or Gold Coast criteria. Annual and cumulative incidence rates were estimated using national population data. Demographic, geographic, and socioeconomic variables were classified under international standards, and all statistical analyses were performed using Python (version 3.12). Results: A total of 2185 ALS cases diagnosed between 1984 and 2024 were included. For the most recent decade (2015-2024), the national cumulative incidence was 41.46 per million inhabitants, with a steady increase in annual incidence. Bogotá and Caldas showed the highest cumulative incidence, whereas Chocó and Casanare reported the lowest. The mean age at diagnosis was 59.9 years, with a slight male predominance (male-to-female ratio 1.11:1). Socioeconomic disparities were evident: 18.0% of patients had no formal education, and over 40% were economically inactive at diagnosis. Conclusions: ALS incidence in Colombia is lower than that reported in high-income regions, but shows pronounced geographic and socioeconomic heterogeneity. These findings underscore the need to strengthen diagnostic capacity, improve equitable access to neurology services, and advance research on environmental and genetic determinants of ALS in Latin America.},
}
RevDate: 2025-12-10
CmpDate: 2025-12-10
Correction: CRISPR-Cas9: bridging the gap between aging mechanisms and therapeutic advances in neurodegenerative disorders.
Frontiers in cellular neuroscience, 19:1739705.
[This corrects the article DOI: 10.3389/fncel.2025.1681891.].
Additional Links: PMID-41368443
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@article {pmid41368443,
year = {2025},
author = {Shamsi, A and Alrouji, M and AlOmeir, O and Tasqeruddin, S and Dinislam, K and Zuberi, A},
title = {Correction: CRISPR-Cas9: bridging the gap between aging mechanisms and therapeutic advances in neurodegenerative disorders.},
journal = {Frontiers in cellular neuroscience},
volume = {19},
number = {},
pages = {1739705},
doi = {10.3389/fncel.2025.1739705},
pmid = {41368443},
issn = {1662-5102},
abstract = {[This corrects the article DOI: 10.3389/fncel.2025.1681891.].},
}
RevDate: 2025-12-10
CmpDate: 2025-12-10
Evaluation of ascending aorta and radial artery elasticity in patients with type 2 diabetes mellitus via velocity vector imaging.
Quantitative imaging in medicine and surgery, 15(12):12044-12054.
BACKGROUND: A decrease in arterial elasticity may contribute to accelerated atherosclerosis, the sequelae of which are the most common causes of death in type 2 diabetes mellitus (T2DM) patients. The aim of this study was to assess ascending aorta (AA) and radial artery (RA) elasticity in T2DM patients via velocity vector imaging (VVI).
METHODS: We enrolled 50 patients with T2DM and 52 age- and sex-matched nondiabetic individuals as controls. All the participants underwent echocardiography and RA ultrasound examinations. AA elasticity parameters, i.e., ascending aortic mean longitudinal strain (ALS), ascending aortic global circumferential strain (ACS), ascending aortic fractional area change (FAC), and RA elasticity parameters, i.e., radial arterial mean longitudinal strain (RLS) and radial arterial global circumferential strain (RCS), were evaluated with VVI. The differences in arterial elasticity parameters between diabetic and non-diabetic patients were evaluated by a paired t-test. Spearman correlation coefficients were calculated to demonstrate the relationship between arterial elasticity parameters and clinical risk factors and cardiovascular biometrics in T2DM patients.
RESULTS: We found that the T2DM group presented significantly lower ALS, ACS, FAC, RLS and RCS values than the control group did (all P<0.05). There were significant associations between all arterial elasticity parameters and glycosylated hemoglobin (HbA1c) and diabetes duration (ALS and HbA1c: r=-0.36, ALS and diabetes duration: r=-0.52, ACS and HbA1c: r=-0.32, ACS and diabetes duration: r=-0.38, FAC and HbA1c: r=-0.36, FAC and diabetes duration: r=-0.32, RLS and HbA1c: r=-0.39, RLS and diabetes duration: r=-0.46, RCS and HbA1c: r=-0.31, RCS and diabetes duration: r=-0.39, respectively; P<0.01). Additionally, the ALS was significantly negatively correlated with fasting plasma glucose (FPG) (r=-0.30, P<0.05).
CONCLUSIONS: The elasticity of the AA and RA in T2DM patients was impaired. Decreased arterial elasticity was associated with poor blood glucose control and a longer duration of diabetes. Further studies are needed to assess the clinical value of VVI findings for predicting future cardiac events.
Additional Links: PMID-41367793
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@article {pmid41367793,
year = {2025},
author = {Yu, L and Yang, Z and Ming, Z and Zeng, S},
title = {Evaluation of ascending aorta and radial artery elasticity in patients with type 2 diabetes mellitus via velocity vector imaging.},
journal = {Quantitative imaging in medicine and surgery},
volume = {15},
number = {12},
pages = {12044-12054},
pmid = {41367793},
issn = {2223-4292},
abstract = {BACKGROUND: A decrease in arterial elasticity may contribute to accelerated atherosclerosis, the sequelae of which are the most common causes of death in type 2 diabetes mellitus (T2DM) patients. The aim of this study was to assess ascending aorta (AA) and radial artery (RA) elasticity in T2DM patients via velocity vector imaging (VVI).
METHODS: We enrolled 50 patients with T2DM and 52 age- and sex-matched nondiabetic individuals as controls. All the participants underwent echocardiography and RA ultrasound examinations. AA elasticity parameters, i.e., ascending aortic mean longitudinal strain (ALS), ascending aortic global circumferential strain (ACS), ascending aortic fractional area change (FAC), and RA elasticity parameters, i.e., radial arterial mean longitudinal strain (RLS) and radial arterial global circumferential strain (RCS), were evaluated with VVI. The differences in arterial elasticity parameters between diabetic and non-diabetic patients were evaluated by a paired t-test. Spearman correlation coefficients were calculated to demonstrate the relationship between arterial elasticity parameters and clinical risk factors and cardiovascular biometrics in T2DM patients.
RESULTS: We found that the T2DM group presented significantly lower ALS, ACS, FAC, RLS and RCS values than the control group did (all P<0.05). There were significant associations between all arterial elasticity parameters and glycosylated hemoglobin (HbA1c) and diabetes duration (ALS and HbA1c: r=-0.36, ALS and diabetes duration: r=-0.52, ACS and HbA1c: r=-0.32, ACS and diabetes duration: r=-0.38, FAC and HbA1c: r=-0.36, FAC and diabetes duration: r=-0.32, RLS and HbA1c: r=-0.39, RLS and diabetes duration: r=-0.46, RCS and HbA1c: r=-0.31, RCS and diabetes duration: r=-0.39, respectively; P<0.01). Additionally, the ALS was significantly negatively correlated with fasting plasma glucose (FPG) (r=-0.30, P<0.05).
CONCLUSIONS: The elasticity of the AA and RA in T2DM patients was impaired. Decreased arterial elasticity was associated with poor blood glucose control and a longer duration of diabetes. Further studies are needed to assess the clinical value of VVI findings for predicting future cardiac events.},
}
RevDate: 2025-12-10
CmpDate: 2025-12-10
Personalized prevention of neurodegenerative diseases: scoping review and evidence gap map.
Alzheimer's & dementia : the journal of the Alzheimer's Association, 21(12):e70980.
Neurodegenerative diseases represent a major public health challenge due to their high prevalence and poor prognosis. Identifying biomarkers to stratify individuals by their risk of developing these diseases may help to define new personalized prevention interventions. The objective of this study was to conduct a scoping review of biomarkers for primary and secondary personalized prevention of neurodegenerative diseases. The search targeted biomarkers in adults or high-risk subpopulations in clinical or public health settings for Alzheimer's disease, vascular dementia, Lewy body disease, frontotemporal dementia, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis. Ultimately, 286 papers were included in the review and the interactive gap map. There is a strong focus on Alzheimer's disease, and most papers included -omics-based biomarkers and/or used artificial intelligence. Genetics/genomics are at the forefront of current scientific research, although there is a notable gap in studying gene-environment interactions, and studies in clinical settings are still scarce. HIGHLIGHTS: Research indicates a strong focus on Alzheimer´s disease and limited research in other diseases. Genetics and genomics are at the forefront of current scientific research. We found biomarkers for predicting progression in mild cognitive decline. There is a notable gap in studying gene-environment interactions. Studies investigating biomarkers in a clinical context are still scarce.
Additional Links: PMID-41366852
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@article {pmid41366852,
year = {2025},
author = {Barahona-López, C and Plans-Beriso, E and Diez-Echave, P and Hernández, O and de Larrea, NF and Craciun, O and García-Ovejero, E and Petrova, D and Fernández-Martínez, NF and Arruabarrena-Blanco, E and Babb-de-Villiers, C and Turner, H and Jimenez, RC and Erady, C and Wilson, H and Fernández-Navarro, P and García-Esquinas, EG and Kuhn, I and Sánchez, P and Rodríguez-Artalejo, F and Sánchez, MJ and Moreno, V and Blackburn, L and Pollán, M and Kroese, M and Perez-Gomez, B},
title = {Personalized prevention of neurodegenerative diseases: scoping review and evidence gap map.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21},
number = {12},
pages = {e70980},
doi = {10.1002/alz.70980},
pmid = {41366852},
issn = {1552-5279},
support = {101057721//Horizon Europe / H2020 Health/ ; 10040946//UKRI/ ; },
mesh = {Humans ; *Neurodegenerative Diseases/prevention & control/genetics ; Biomarkers ; *Precision Medicine/methods ; Evidence Gaps ; },
abstract = {Neurodegenerative diseases represent a major public health challenge due to their high prevalence and poor prognosis. Identifying biomarkers to stratify individuals by their risk of developing these diseases may help to define new personalized prevention interventions. The objective of this study was to conduct a scoping review of biomarkers for primary and secondary personalized prevention of neurodegenerative diseases. The search targeted biomarkers in adults or high-risk subpopulations in clinical or public health settings for Alzheimer's disease, vascular dementia, Lewy body disease, frontotemporal dementia, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis. Ultimately, 286 papers were included in the review and the interactive gap map. There is a strong focus on Alzheimer's disease, and most papers included -omics-based biomarkers and/or used artificial intelligence. Genetics/genomics are at the forefront of current scientific research, although there is a notable gap in studying gene-environment interactions, and studies in clinical settings are still scarce. HIGHLIGHTS: Research indicates a strong focus on Alzheimer´s disease and limited research in other diseases. Genetics and genomics are at the forefront of current scientific research. We found biomarkers for predicting progression in mild cognitive decline. There is a notable gap in studying gene-environment interactions. Studies investigating biomarkers in a clinical context are still scarce.},
}
MeSH Terms:
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Humans
*Neurodegenerative Diseases/prevention & control/genetics
Biomarkers
*Precision Medicine/methods
Evidence Gaps
RevDate: 2025-12-10
CmpDate: 2025-12-10
Quantifying multimodal longitudinal brain changes in presymptomatic C9orf72 disease.
Alzheimer's & dementia : the journal of the Alzheimer's Association, 21(12):e70902.
INTRODUCTION: The presymptomatic phase of frontotemporal dementia and amyotrophic lateral sclerosis associated with C9orf72 repeat expansion features widespread structural brain changes. We aimed at fulfilling the unmet need of quantitative magnetic resonance imaging (MRI)-derived measures suitable for disease tracking.
METHODS: We compared the profile of longitudinal gray (GM) and white matter (WM) changes in 66 presymptomatic carriers and 52 controls over 3-year follow-up and appraised their annualized rate of change (ARC).
RESULTS: Both putamen (p < 0.01) and left insula (p = 0.005) volumes declined the most in carriers over 40, with an ARC up to four-fold higher than in controls. Increases in mean diffusivity occurred first in the left uncinate fasciculus, followed by thalamo-cortical bundles (p < 0.05), associated with higher neurofilament levels.
DISCUSSION: Our study highlighted the GM and WM structures showing the greatest longitudinal decline during the preclinical stage, whose ARC may serve as an MRI-derived biomarker for longitudinal surveillance and therapeutic outcome.
CLINICAL TRIAL REGISTRATION: NCT02590276 and NCT05358431.
HIGHLIGHTS: We studied longitudinal multimodal MRI changes in presymptomatic C9orf72 disease. Carriers displayed faster atrophy in putamen, insula and cerebellar regions. Mean diffusivity increased mainly in uncinate and thalamo-cortical tracts. These differences were even more significant in older (> 40) participants. We proposed targeted annualized rate of change as a quantitative biomarker.
Additional Links: PMID-41366786
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@article {pmid41366786,
year = {2025},
author = {Saracino, D and Cipriano, L and Houot, M and Querin, G and Rinaldi, D and Rametti-Lacroux, A and Wallon, D and Gerardin, E and Couratier, P and Boncoeur, MP and Lebouvier, T and , and Colliot, O and Pradat, PF and Migliaccio, R and Le Ber, I},
title = {Quantifying multimodal longitudinal brain changes in presymptomatic C9orf72 disease.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21},
number = {12},
pages = {e70902},
doi = {10.1002/alz.70902},
pmid = {41366786},
issn = {1552-5279},
support = {PRTS2015-2019PREV-DEMALS//ANR/DGOS - Assistance Publique-Hôpitaux de Paris (Dr Le Ber)/ ; ANR-10-IAIHU-06//Agence Nationale de la Recherche (Dr Le Ber)/ ; 2019-JPW2-0005-01STRATALS//JPND/ANR (Dr Pradat and Dr Le Ber)/ ; ANR-23-IACL-0008, PRAIRIE-PSAI//Agence Nationale de la Recherche as part of the "France 2030" program/ ; ANR-19-P3IA-0001, projectPRAIRIE3IAInstitute//Agence Nationale de la Recherche as part of the "Investissements d'avenir" program/ ; 101136607, projectCLARA//European Union's HORIZON EUROPE Framework Programme/ ; },
mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/genetics/diagnostic imaging/pathology ; *Brain/pathology/diagnostic imaging ; *C9orf72 Protein/genetics ; Disease Progression ; *Frontotemporal Dementia/genetics/diagnostic imaging/pathology ; *Gray Matter/pathology/diagnostic imaging ; Longitudinal Studies ; Magnetic Resonance Imaging ; *White Matter/pathology/diagnostic imaging ; },
abstract = {INTRODUCTION: The presymptomatic phase of frontotemporal dementia and amyotrophic lateral sclerosis associated with C9orf72 repeat expansion features widespread structural brain changes. We aimed at fulfilling the unmet need of quantitative magnetic resonance imaging (MRI)-derived measures suitable for disease tracking.
METHODS: We compared the profile of longitudinal gray (GM) and white matter (WM) changes in 66 presymptomatic carriers and 52 controls over 3-year follow-up and appraised their annualized rate of change (ARC).
RESULTS: Both putamen (p < 0.01) and left insula (p = 0.005) volumes declined the most in carriers over 40, with an ARC up to four-fold higher than in controls. Increases in mean diffusivity occurred first in the left uncinate fasciculus, followed by thalamo-cortical bundles (p < 0.05), associated with higher neurofilament levels.
DISCUSSION: Our study highlighted the GM and WM structures showing the greatest longitudinal decline during the preclinical stage, whose ARC may serve as an MRI-derived biomarker for longitudinal surveillance and therapeutic outcome.
CLINICAL TRIAL REGISTRATION: NCT02590276 and NCT05358431.
HIGHLIGHTS: We studied longitudinal multimodal MRI changes in presymptomatic C9orf72 disease. Carriers displayed faster atrophy in putamen, insula and cerebellar regions. Mean diffusivity increased mainly in uncinate and thalamo-cortical tracts. These differences were even more significant in older (> 40) participants. We proposed targeted annualized rate of change as a quantitative biomarker.},
}
MeSH Terms:
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Aged
Female
Humans
Male
Middle Aged
*Amyotrophic Lateral Sclerosis/genetics/diagnostic imaging/pathology
*Brain/pathology/diagnostic imaging
*C9orf72 Protein/genetics
Disease Progression
*Frontotemporal Dementia/genetics/diagnostic imaging/pathology
*Gray Matter/pathology/diagnostic imaging
Longitudinal Studies
Magnetic Resonance Imaging
*White Matter/pathology/diagnostic imaging
RevDate: 2025-12-10
Safety and efficacy of botulinum toxin injection for sialorrhea in amyotrophic lateral sclerosis: a systematic review and meta-analysis.
BMC neurology, 25(1):496.
Additional Links: PMID-41366746
PubMed:
Citation:
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@article {pmid41366746,
year = {2025},
author = {Huang, J and Liu, Y and Li, M and He, R and Tang, Z and Lei, Y and Zha, Y and Wei, J},
title = {Safety and efficacy of botulinum toxin injection for sialorrhea in amyotrophic lateral sclerosis: a systematic review and meta-analysis.},
journal = {BMC neurology},
volume = {25},
number = {1},
pages = {496},
pmid = {41366746},
issn = {1471-2377},
}
RevDate: 2025-12-09
Assessment of tracheal mucosal thicknesses is a preferable method for evaluation of the immunogenicity of Mycoplasma gallisepticum vaccines in poultry.
Vaccine, 72:128063 pii:S0264-410X(25)01361-1 [Epub ahead of print].
Live-attenuated vaccines are commonly used to control chronic respiratory disease (CRD) caused by Mycoplasma gallisepticum in poultry. A previous review found that measures of tracheal lesions are better indicators of the validity of a vaccine efficacy test than air sac lesions. Here we extend those observations by comparing the raw tracheal mucosal thickness (TMT) and gross air sac lesion score (ALS) data from published vaccine efficacy studies to provide insights into standardising methods for evaluation of M. gallisepticum vaccine efficacy by identifying the most discriminative and reproducible parameter to demonstrate the efficacy of vaccines and the validity of immunogenicity tests. Our analyses revealed that a higher proportion of trials detected a ≥ 80 % effectiveness of challenge based on TMT, with a significantly lower number of biological replicates, than ALS. Furthermore, a significantly higher proportion of vaccinated-and-challenged groups had a proportion protected of ≥80 %, a reduction in lesions of ≥30 % and a mitigated fraction of ≥0.80, with a significantly lower number of biological replicates, compared to the positive-control group when analyses were based on TMT rather than ALSs. These findings indicate that TMT is a more discriminative and reproducible parameter to assess the efficacy of a vaccine and the validity of an efficacy test, and hence that this should be the primary outcome variable used to evaluate M. gallisepticum vaccine efficacy studies. Furthermore, the ability of TMT to discriminate these groups with fewer biological replicates enhances animal welfare by reducing the number of animals needed for efficacy studies.
Additional Links: PMID-41365127
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PubMed:
Citation:
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@article {pmid41365127,
year = {2025},
author = {Kulappu Arachchige, SN and Abeykoon, AMH and Stevenson, MA and Kanci Condello, A and Shil, PK and Tulman, ER and Szczepanek, SM and Silbart, LK and Underwood, GJ and Noormohammadi, AH and Geary, SJ and Wawegama, NK and Browning, GF},
title = {Assessment of tracheal mucosal thicknesses is a preferable method for evaluation of the immunogenicity of Mycoplasma gallisepticum vaccines in poultry.},
journal = {Vaccine},
volume = {72},
number = {},
pages = {128063},
doi = {10.1016/j.vaccine.2025.128063},
pmid = {41365127},
issn = {1873-2518},
abstract = {Live-attenuated vaccines are commonly used to control chronic respiratory disease (CRD) caused by Mycoplasma gallisepticum in poultry. A previous review found that measures of tracheal lesions are better indicators of the validity of a vaccine efficacy test than air sac lesions. Here we extend those observations by comparing the raw tracheal mucosal thickness (TMT) and gross air sac lesion score (ALS) data from published vaccine efficacy studies to provide insights into standardising methods for evaluation of M. gallisepticum vaccine efficacy by identifying the most discriminative and reproducible parameter to demonstrate the efficacy of vaccines and the validity of immunogenicity tests. Our analyses revealed that a higher proportion of trials detected a ≥ 80 % effectiveness of challenge based on TMT, with a significantly lower number of biological replicates, than ALS. Furthermore, a significantly higher proportion of vaccinated-and-challenged groups had a proportion protected of ≥80 %, a reduction in lesions of ≥30 % and a mitigated fraction of ≥0.80, with a significantly lower number of biological replicates, compared to the positive-control group when analyses were based on TMT rather than ALSs. These findings indicate that TMT is a more discriminative and reproducible parameter to assess the efficacy of a vaccine and the validity of an efficacy test, and hence that this should be the primary outcome variable used to evaluate M. gallisepticum vaccine efficacy studies. Furthermore, the ability of TMT to discriminate these groups with fewer biological replicates enhances animal welfare by reducing the number of animals needed for efficacy studies.},
}
RevDate: 2025-12-09
Reporting quality standards in gaming disorder treatment evidence: A systematic review.
Acta psychologica, 262:106063 pii:S0001-6918(25)01377-0 [Epub ahead of print].
BACKGROUND: The treatment evidence base for gaming disorder (GD) has grown steadily over the past two decades. A systematic review by King et al. (2017) of 30 studies reported that GD treatment studies tended to favor psychotherapy approaches, but the research was limited by poor reporting standards as assessed by the Consolidated Standards of Reporting Trials (CONSORT) framework. This systematic review aimed to conduct a follow up evaluation of the reporting quality of subsequent GD treatment studies.
METHODS: A literature search of six databases yielded 51,056 records, which resulted in 31 eligible studies after screening. Each study's reporting quality was assessed using the CONSORT statement, and then these assessments were compared to King et al.'s (2017) review.
RESULTS: This review identified several methodological improvements since 2017: 61 % of studies were randomized controlled trials (vs. 40 % in 2017), 90 % included control groups (vs. 63 %), and follow-up duration increased to 6.1 months (vs. 3.5 months; p = .032). Reporting improved for participant flow (87.1 % vs. 43.3 %; p = .001) and group-level statistics (74.2 % vs. 36.7 %; p = .003), but some areas showed no improvement.
DISCUSSION: There have been several improvements in GD treatment study design and reporting, including controls, randomization and follow up, reflecting an increasing number of higher quality trials for the condition. Most of the studies with higher reporting quality (i.e., scoring ≥30/46 on the CONSORT framework) were psychotherapy-based. Future research should employ designs with longer follow-ups, broader assessment of outcomes, and standardized ICD-11-aligned tools. Pharmacological treatments, including novel pharmacotherapies for other addictions (e.g., Naltrexone), are underexplored and lack high quality evidence.
Additional Links: PMID-41365015
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PubMed:
Citation:
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@article {pmid41365015,
year = {2025},
author = {Svendsen, O and Stevens, MWR and Hamamura, T and Harpas, I and Radunz, M and King, DL},
title = {Reporting quality standards in gaming disorder treatment evidence: A systematic review.},
journal = {Acta psychologica},
volume = {262},
number = {},
pages = {106063},
doi = {10.1016/j.actpsy.2025.106063},
pmid = {41365015},
issn = {1873-6297},
abstract = {BACKGROUND: The treatment evidence base for gaming disorder (GD) has grown steadily over the past two decades. A systematic review by King et al. (2017) of 30 studies reported that GD treatment studies tended to favor psychotherapy approaches, but the research was limited by poor reporting standards as assessed by the Consolidated Standards of Reporting Trials (CONSORT) framework. This systematic review aimed to conduct a follow up evaluation of the reporting quality of subsequent GD treatment studies.
METHODS: A literature search of six databases yielded 51,056 records, which resulted in 31 eligible studies after screening. Each study's reporting quality was assessed using the CONSORT statement, and then these assessments were compared to King et al.'s (2017) review.
RESULTS: This review identified several methodological improvements since 2017: 61 % of studies were randomized controlled trials (vs. 40 % in 2017), 90 % included control groups (vs. 63 %), and follow-up duration increased to 6.1 months (vs. 3.5 months; p = .032). Reporting improved for participant flow (87.1 % vs. 43.3 %; p = .001) and group-level statistics (74.2 % vs. 36.7 %; p = .003), but some areas showed no improvement.
DISCUSSION: There have been several improvements in GD treatment study design and reporting, including controls, randomization and follow up, reflecting an increasing number of higher quality trials for the condition. Most of the studies with higher reporting quality (i.e., scoring ≥30/46 on the CONSORT framework) were psychotherapy-based. Future research should employ designs with longer follow-ups, broader assessment of outcomes, and standardized ICD-11-aligned tools. Pharmacological treatments, including novel pharmacotherapies for other addictions (e.g., Naltrexone), are underexplored and lack high quality evidence.},
}
RevDate: 2025-12-09
Evaluating the generalizability of the normative odor rating across cultures: Evidence from a German-speaking sample.
Acta psychologica, 262:106056 pii:S0001-6918(25)01370-8 [Epub ahead of print].
Olfactory perception varies across cultures, yet the cross-cultural generalizability of normative odor ratings remains underexplored. This study investigates the generalizability of normative odor ratings to a German-speaking sample by assessing 24 odors across eight dimensions-familiarity, frequency, pleasantness, irritability, context availability, discriminability, age of acquisition, and verbalizability-in 124 German-speaking participants (Mage = 22.36, SD = 3.24). Building on Moss et al.'s (2016) methodology with English-speaking participants, we examined the consistency of these dimensions, the influence of odor familiarity, and the role of odor-specific properties versus individual differences. Results revealed significant intercorrelations among the dimensions, except for age of acquisition, which negatively correlated with others, confirming the importance of early exposure in olfactory perceptual saliency and linguistic accessibility. For high-familiar odors, strong correlations with Moss et al.'s ratings were found for familiarity (r = 0.805), frequency (r = 0.799), pleasantness (r = 0.792), context availability (r = 0.794), discriminability (r = 0.967), and verbalizability (r = 0.844), and age of acquisition (r = 0.750), but not for irritability (r = 0.495). Low-familiar odors showed only a moderate correlation for verbalizability (r = 0.530), highlighting the role of exposure in cross-cultural consistency. Variance across odors significantly exceeded variance across participants, indicating reliable differentiation by odor properties. These findings suggest that normative odor ratings show strong cross-sample consistency across the two samples, particularly for familiar odors. This study supports the utility of normative ratings in olfactory research while highlighting the role of familiarity and context in cross-cultural perception.
Additional Links: PMID-41365006
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PubMed:
Citation:
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@article {pmid41365006,
year = {2025},
author = {Hamzeloo, M and Bogenschütz, L and Hackländer, RPM and Bermeitinger, C},
title = {Evaluating the generalizability of the normative odor rating across cultures: Evidence from a German-speaking sample.},
journal = {Acta psychologica},
volume = {262},
number = {},
pages = {106056},
doi = {10.1016/j.actpsy.2025.106056},
pmid = {41365006},
issn = {1873-6297},
abstract = {Olfactory perception varies across cultures, yet the cross-cultural generalizability of normative odor ratings remains underexplored. This study investigates the generalizability of normative odor ratings to a German-speaking sample by assessing 24 odors across eight dimensions-familiarity, frequency, pleasantness, irritability, context availability, discriminability, age of acquisition, and verbalizability-in 124 German-speaking participants (Mage = 22.36, SD = 3.24). Building on Moss et al.'s (2016) methodology with English-speaking participants, we examined the consistency of these dimensions, the influence of odor familiarity, and the role of odor-specific properties versus individual differences. Results revealed significant intercorrelations among the dimensions, except for age of acquisition, which negatively correlated with others, confirming the importance of early exposure in olfactory perceptual saliency and linguistic accessibility. For high-familiar odors, strong correlations with Moss et al.'s ratings were found for familiarity (r = 0.805), frequency (r = 0.799), pleasantness (r = 0.792), context availability (r = 0.794), discriminability (r = 0.967), and verbalizability (r = 0.844), and age of acquisition (r = 0.750), but not for irritability (r = 0.495). Low-familiar odors showed only a moderate correlation for verbalizability (r = 0.530), highlighting the role of exposure in cross-cultural consistency. Variance across odors significantly exceeded variance across participants, indicating reliable differentiation by odor properties. These findings suggest that normative odor ratings show strong cross-sample consistency across the two samples, particularly for familiar odors. This study supports the utility of normative ratings in olfactory research while highlighting the role of familiarity and context in cross-cultural perception.},
}
RevDate: 2025-12-09
Correlations of cerebrospinal fluid neurofilament light chain levels with clinical and electromyography findings in amyotrophic lateral sclerosis.
Irish journal of medical science [Epub ahead of print].
BACKGROUND: This study aimed to examine correlations between cerebrospinal fluid neurofilament light chain (CSF NfL) levels, and clinical and electrophysiological findings in amyotrophic lateral sclerosis (ALS). Compare CSF NfL and total protein levels between ALS and other central nervous system (CNS) neurodegenerative disorders.
METHODS: This retrospective study analyzed 46 ALS patients (Gold Coast criteria) and 33 non-ALS neurodegenerative controls. We documented time from symptom onset to diagnosis, revised ALS Functional Rating Scale (ALSFRS-R) scores at CSF sampling, initial involvement regions (bulbar/cervical/lumbosacral), and extent of lower motor neuron (LMN) involvement.
RESULTS: ALS patients had significantly higher CSF NfL levels than non-ALS controls (4221 ± 2585 vs. 3004 ± 2788 pg/mL, p = 0.025). In the ALS group, CSF NfL levels showed significant inverse correlation with ALSFRS-R scores (r = -0.332, p = 0.024), and patients demonstrating involvement in all four-region on needle electromyography exhibited the highest CSF NfL levels. Among the ALS cohort 18 patients (39%) had died by the last follow-up, and patients who died during the study exhibited significantly higher baseline CSF NfL levels (median: 5115 pg/mL) compared to surviving patients (median: 3276 pg/mL; p = 0.007).
CONCLUSIONS: Our study demonstrated that CSF NFL levels were significantly elevated in ALS compared to other neurodegenerative disorders. Higher CSF NFL concentrations correlated with more rapid functional decline, more extensive LMN degeneration, and poorer survival outcomes.
Additional Links: PMID-41364409
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@article {pmid41364409,
year = {2025},
author = {Matur, Z and Deveci, Ş and Erdal, Y},
title = {Correlations of cerebrospinal fluid neurofilament light chain levels with clinical and electromyography findings in amyotrophic lateral sclerosis.},
journal = {Irish journal of medical science},
volume = {},
number = {},
pages = {},
pmid = {41364409},
issn = {1863-4362},
abstract = {BACKGROUND: This study aimed to examine correlations between cerebrospinal fluid neurofilament light chain (CSF NfL) levels, and clinical and electrophysiological findings in amyotrophic lateral sclerosis (ALS). Compare CSF NfL and total protein levels between ALS and other central nervous system (CNS) neurodegenerative disorders.
METHODS: This retrospective study analyzed 46 ALS patients (Gold Coast criteria) and 33 non-ALS neurodegenerative controls. We documented time from symptom onset to diagnosis, revised ALS Functional Rating Scale (ALSFRS-R) scores at CSF sampling, initial involvement regions (bulbar/cervical/lumbosacral), and extent of lower motor neuron (LMN) involvement.
RESULTS: ALS patients had significantly higher CSF NfL levels than non-ALS controls (4221 ± 2585 vs. 3004 ± 2788 pg/mL, p = 0.025). In the ALS group, CSF NfL levels showed significant inverse correlation with ALSFRS-R scores (r = -0.332, p = 0.024), and patients demonstrating involvement in all four-region on needle electromyography exhibited the highest CSF NfL levels. Among the ALS cohort 18 patients (39%) had died by the last follow-up, and patients who died during the study exhibited significantly higher baseline CSF NfL levels (median: 5115 pg/mL) compared to surviving patients (median: 3276 pg/mL; p = 0.007).
CONCLUSIONS: Our study demonstrated that CSF NFL levels were significantly elevated in ALS compared to other neurodegenerative disorders. Higher CSF NFL concentrations correlated with more rapid functional decline, more extensive LMN degeneration, and poorer survival outcomes.},
}
RevDate: 2025-12-09
U.S. health plan coverage of Neuromuscular Disease Therapies: An assessment of policy availability and restrictions.
Journal of neuromuscular diseases [Epub ahead of print].
BACKGROUND: Health plan policies managing neuromuscular disease (NMD) therapies may impose burdensome requirements on patients and providers. While prior research has explored payer restrictions for rare NMD treatments, limited evidence exists on policies specifically governing therapy initiation and reauthorization.
OBJECTIVES: To examine initial and reauthorization coverage policies for therapies targeting five NMDs-Duchenne muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy, generalized myasthenia gravis, and Lambert-Eaton myasthenic syndrome-across all U.S. state Medicaid programs and leading commercial health plans.
METHODS: We constructed a database of coverage decisions issued by 50 states and DC Medicaid programs and 35 major commercial insurers, including both fee-for-service and managed care organizations. We analyzed (1) policy availability and coverage frequency, (2) initial coverage requirements (e.g., subgroup restrictions, step therapy, prescriber type), (3) reauthorization criteria, and (4) approval durations.
RESULTS: Of 1204 potential decisions, 908 (75%) had publicly available policies. Of these, 558 (46%) included reauthorization criteria. Among covered therapies, 96% imposed restrictions beyond FDA label indications. Requirements varied by payer type, NMD, and therapy. Average approval durations were 6 months for initial coverage and 10 months for reauthorization.
CONCLUSIONS: Many plans lacked publicly accessible policies, and most covered therapies were subject to restrictive requirements. These barriers-such as step therapy, narrow prescriber criteria, and short approval periods-may delay treatment and disrupt care continuity. Findings underscore the need for greater transparency and reform in prior authorization and pharmacy benefit design to support timely access to NMD therapies.
Additional Links: PMID-41364388
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@article {pmid41364388,
year = {2025},
author = {Levine, AA and Rucker, JA and Cockerham, A and Cartner, J and Chambers, JD},
title = {U.S. health plan coverage of Neuromuscular Disease Therapies: An assessment of policy availability and restrictions.},
journal = {Journal of neuromuscular diseases},
volume = {},
number = {},
pages = {22143602251405815},
doi = {10.1177/22143602251405815},
pmid = {41364388},
issn = {2214-3602},
abstract = {BACKGROUND: Health plan policies managing neuromuscular disease (NMD) therapies may impose burdensome requirements on patients and providers. While prior research has explored payer restrictions for rare NMD treatments, limited evidence exists on policies specifically governing therapy initiation and reauthorization.
OBJECTIVES: To examine initial and reauthorization coverage policies for therapies targeting five NMDs-Duchenne muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy, generalized myasthenia gravis, and Lambert-Eaton myasthenic syndrome-across all U.S. state Medicaid programs and leading commercial health plans.
METHODS: We constructed a database of coverage decisions issued by 50 states and DC Medicaid programs and 35 major commercial insurers, including both fee-for-service and managed care organizations. We analyzed (1) policy availability and coverage frequency, (2) initial coverage requirements (e.g., subgroup restrictions, step therapy, prescriber type), (3) reauthorization criteria, and (4) approval durations.
RESULTS: Of 1204 potential decisions, 908 (75%) had publicly available policies. Of these, 558 (46%) included reauthorization criteria. Among covered therapies, 96% imposed restrictions beyond FDA label indications. Requirements varied by payer type, NMD, and therapy. Average approval durations were 6 months for initial coverage and 10 months for reauthorization.
CONCLUSIONS: Many plans lacked publicly accessible policies, and most covered therapies were subject to restrictive requirements. These barriers-such as step therapy, narrow prescriber criteria, and short approval periods-may delay treatment and disrupt care continuity. Findings underscore the need for greater transparency and reform in prior authorization and pharmacy benefit design to support timely access to NMD therapies.},
}
RevDate: 2025-12-09
Evaluation of pathogenicity, host resistance, biological properties and chemical control of Xanthomonas fragariae Strain JD1 causing angular leaf spot on strawberry.
Plant disease [Epub ahead of print].
Angular leaf spot (ALS), caused by the quarantine pathogen Xanthomonas fragariae, is a major bacterial disease threatening global strawberry production. In China, its continued spread across multiple regions poses a significant and persistent epidemiological threat to the strawberry industry. Recently, ALS has emerged as a great threat to strawberry industry in the Jiande, Zhejiang province (located at 29°N, 119°E). This study reports the first isolation and characterization of X. fragariae strain JD1 from symptomatic strawberry leaves in Jiande, Zhejiang Province. The identification of strain JD1 was confirmed through species-specific PCR, analysis of colony characteristics, and phylogenetic clustering based on 16S rRNA and HrpB gene sequences. Pathogenicity assays revealed strain JD1 resulted in water-soaked lesions progressing to necrotic patches on leaves, along with systemic colonization of crown tissues showing water-soaked, reddish-brown lesions without cavity formation. Additionally, resistance evaluation across six strawberry cultivars revealed that 'Yue Xiu' was the most susceptible, followed closely by 'Jiande Hong', 'Hong Yu', 'Li Fen', and 'Hong Yan', while 'Fen Yu' exhibited the highest resistance. Biological characterization showed that strain JD1 grows optimally at 25°C and pH 7.0, with significant inhibition observed at 35°C and under acidic (pH 4) or alkaline (pH 9) conditions. In bactericide screening, tetramycin and benziothiazolinone were identified as highly effective against JD, followed by sintracin acetate aqueous with minor efficacy, whereas kasugamycin and quinoline copper showed limited or no efficacy. Collectively, these findings not only emphasize the threat posed by X. fragariae strain JD1 to strawberry production but also provide critical insights that inform integrated management strategies, including the use of resistant cultivars, environmental controls, and targeted bactericides, for controlling ALS.
Additional Links: PMID-41362129
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PubMed:
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@article {pmid41362129,
year = {2025},
author = {Ma, T and Zhu, H and Zhu, J and Zhao, J and Zhao, X},
title = {Evaluation of pathogenicity, host resistance, biological properties and chemical control of Xanthomonas fragariae Strain JD1 causing angular leaf spot on strawberry.},
journal = {Plant disease},
volume = {},
number = {},
pages = {},
doi = {10.1094/PDIS-10-25-2070-RE},
pmid = {41362129},
issn = {0191-2917},
abstract = {Angular leaf spot (ALS), caused by the quarantine pathogen Xanthomonas fragariae, is a major bacterial disease threatening global strawberry production. In China, its continued spread across multiple regions poses a significant and persistent epidemiological threat to the strawberry industry. Recently, ALS has emerged as a great threat to strawberry industry in the Jiande, Zhejiang province (located at 29°N, 119°E). This study reports the first isolation and characterization of X. fragariae strain JD1 from symptomatic strawberry leaves in Jiande, Zhejiang Province. The identification of strain JD1 was confirmed through species-specific PCR, analysis of colony characteristics, and phylogenetic clustering based on 16S rRNA and HrpB gene sequences. Pathogenicity assays revealed strain JD1 resulted in water-soaked lesions progressing to necrotic patches on leaves, along with systemic colonization of crown tissues showing water-soaked, reddish-brown lesions without cavity formation. Additionally, resistance evaluation across six strawberry cultivars revealed that 'Yue Xiu' was the most susceptible, followed closely by 'Jiande Hong', 'Hong Yu', 'Li Fen', and 'Hong Yan', while 'Fen Yu' exhibited the highest resistance. Biological characterization showed that strain JD1 grows optimally at 25°C and pH 7.0, with significant inhibition observed at 35°C and under acidic (pH 4) or alkaline (pH 9) conditions. In bactericide screening, tetramycin and benziothiazolinone were identified as highly effective against JD, followed by sintracin acetate aqueous with minor efficacy, whereas kasugamycin and quinoline copper showed limited or no efficacy. Collectively, these findings not only emphasize the threat posed by X. fragariae strain JD1 to strawberry production but also provide critical insights that inform integrated management strategies, including the use of resistant cultivars, environmental controls, and targeted bactericides, for controlling ALS.},
}
RevDate: 2025-12-09
Utility of patient subgrouping in ALS clinical trials: a World Federation of Neurology white paper.
Amyotrophic lateral sclerosis & frontotemporal degeneration [Epub ahead of print].
The heterogeneity among the amyotrophic lateral sclerosis (ALS)/MND patient population is well recognized but not well understood. Such heterogeneity may represent a significant confound in our current and prior clinical trials as certain subgroups of patients might have a selective response (or resistance) to a novel therapeutic. The basis on which to segregate the patient population is, however, unclear. The ALS/MND Committee of the World Federation of Neurology (WFN) convened a symposium to discuss various strategies that might be considered for separating (stratifying) the population to further study. The results of that conference are presented here as a white paper, reflecting current understanding of several of the various criteria that could be implemented to divide the patient population as presented and discussed at that meeting. Consideration of grouping patients based on phenotype, cognitive involvement, imaging, or electrophysiology is presented here.
Additional Links: PMID-41361897
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PubMed:
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@article {pmid41361897,
year = {2025},
author = {Rosenfeld, J and Abrahams, S and McHutchinson, C and Ajroud-Driss, S and Weber, M and Paganoni, S and Mitsumoto, H and Genge, A and Grosskreutz, J and Van Den Berg, L and Andrews, J and Kiernan, MC},
title = {Utility of patient subgrouping in ALS clinical trials: a World Federation of Neurology white paper.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-8},
doi = {10.1080/21678421.2025.2593308},
pmid = {41361897},
issn = {2167-9223},
abstract = {The heterogeneity among the amyotrophic lateral sclerosis (ALS)/MND patient population is well recognized but not well understood. Such heterogeneity may represent a significant confound in our current and prior clinical trials as certain subgroups of patients might have a selective response (or resistance) to a novel therapeutic. The basis on which to segregate the patient population is, however, unclear. The ALS/MND Committee of the World Federation of Neurology (WFN) convened a symposium to discuss various strategies that might be considered for separating (stratifying) the population to further study. The results of that conference are presented here as a white paper, reflecting current understanding of several of the various criteria that could be implemented to divide the patient population as presented and discussed at that meeting. Consideration of grouping patients based on phenotype, cognitive involvement, imaging, or electrophysiology is presented here.},
}
RevDate: 2025-12-09
Erratum.
Neuro-degenerative diseases, 25(4):227.
In the article "Characteristics of Neuromuscular Ultrasound in Patients with Amyotrophic Lateral Sclerosis" [Neurodegener Dis. 2025;
The original online article has been updated to reflect this.
Additional Links: PMID-41191543
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@article {pmid41191543,
year = {2025},
author = {},
title = {Erratum.},
journal = {Neuro-degenerative diseases},
volume = {25},
number = {4},
pages = {227},
doi = {10.1159/000548749},
pmid = {41191543},
issn = {1660-2862},
abstract = {
In the article "Characteristics of Neuromuscular Ultrasound in Patients with Amyotrophic Lateral Sclerosis" [Neurodegener Dis. 2025;
The original online article has been updated to reflect this.
RevDate: 2025-12-08
CmpDate: 2025-12-08
An open dataset of multidimensional signals based on different speech patterns in pragmatic Mandarin.
Scientific data, 12(1):1934.
Speech is essential for human communication, but millions of people lose the ability to speak due to conditions such as amyotrophic lateral sclerosis (ALS) or stroke. Assistive technologies like brain-computer interfaces (BCIs), can convert brain signals into speech. However, these technologies still face challenges in decoding accuracy. This issue is especially challenging for tonal languages like Mandarin Chinese. Furthermore, most existing speech datasets are based on Indo-European languages, which hinders our understanding of how tonal information is encoded in the brain. To address this, we introduce a comprehensive open dataset, which includes multimodal signals from 30 subjects using Mandarin Chinese across overt, silent, and imagined speech modes, covering electroencephalogram (EEG), surface electromyogram (sEMG), and speech recordings. This dataset lays a valuable groundwork for exploring the neural encoding of tonal languages, investigating tone-related brain dynamics, and improving assistive communication strategies. It supports cross-linguistic speech processing research and contributes to data-driven neural speech decoding technology innovations.
Additional Links: PMID-41361196
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@article {pmid41361196,
year = {2025},
author = {Zhao, R and Bai, Y and Zhang, S and Zhu, J and Liu, H and Ni, G},
title = {An open dataset of multidimensional signals based on different speech patterns in pragmatic Mandarin.},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {1934},
pmid = {41361196},
issn = {2052-4463},
mesh = {Humans ; *Speech ; Electroencephalography ; *Language ; Brain-Computer Interfaces ; Electromyography ; China ; Brain/physiology ; },
abstract = {Speech is essential for human communication, but millions of people lose the ability to speak due to conditions such as amyotrophic lateral sclerosis (ALS) or stroke. Assistive technologies like brain-computer interfaces (BCIs), can convert brain signals into speech. However, these technologies still face challenges in decoding accuracy. This issue is especially challenging for tonal languages like Mandarin Chinese. Furthermore, most existing speech datasets are based on Indo-European languages, which hinders our understanding of how tonal information is encoded in the brain. To address this, we introduce a comprehensive open dataset, which includes multimodal signals from 30 subjects using Mandarin Chinese across overt, silent, and imagined speech modes, covering electroencephalogram (EEG), surface electromyogram (sEMG), and speech recordings. This dataset lays a valuable groundwork for exploring the neural encoding of tonal languages, investigating tone-related brain dynamics, and improving assistive communication strategies. It supports cross-linguistic speech processing research and contributes to data-driven neural speech decoding technology innovations.},
}
MeSH Terms:
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Humans
*Speech
Electroencephalography
*Language
Brain-Computer Interfaces
Electromyography
China
Brain/physiology
RevDate: 2025-12-08
CmpDate: 2025-12-08
Reply to: Methodological Issues in Taquet et al.'s analysis preclude any conclusions regarding AS01 adjuvant's specific role in dementia prevention.
NPJ vaccines, 10(1):256.
Additional Links: PMID-41361184
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@article {pmid41361184,
year = {2025},
author = {Taquet, M and Todd, JA and Harrison, PJ},
title = {Reply to: Methodological Issues in Taquet et al.'s analysis preclude any conclusions regarding AS01 adjuvant's specific role in dementia prevention.},
journal = {NPJ vaccines},
volume = {10},
number = {1},
pages = {256},
pmid = {41361184},
issn = {2059-0105},
}
RevDate: 2025-12-08
Anionic Liposomes as Optimal Membrane Fusion Carriers Enabling in Situ Multiplexed Detection of Extracellular Vesicle MicroRNAs.
Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Epub ahead of print].
Extracellular vesicle (EV) microRNAs (miRNAs) are promising liquid biopsy biomarkers for non-invasive diagnosis, monitoring, and therapeutic evaluation of cancer. However, sensitive EV miRNA detection is hindered by complex pre-analytical processing. Here, the authors present an anionic liposome (AL) assisted membrane fusion strategy enabling one-step multiplexed quantification of EV miRNAs directly from plasma without EV isolation or RNA extraction, termed EValarm (Anionic Liposome Assisted miRNAs Monitoring for Extracellular Vesicles). Liposomes encapsulating probes are prepared using a microfluidic chip, achieving catalytic signal amplification after target recognition of miRNA. Systematic lipid screening identified ALs as optimal carriers, exhibiting minimal background and superior sensitivity compared to cationic and neutral liposomes. The AL-based assay delivered accuracy comparable to quantitative PCR with a streamlined workflow. Applied to 106 clinical samples from lymphoma patients and healthy controls, integration with artificial intelligence achieved high accuracy (AUC > 0.99). In summary, this study demonstrates a platform enabling direct and sensitive plasma EV miRNA detection, offering strong potential for clinical translation in cancer liquid biopsy.
Additional Links: PMID-41360752
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PubMed:
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@article {pmid41360752,
year = {2025},
author = {Ma, JY and Wang, X and Cai, Y and Wang, G and Lu, M and Feng, K and Zhao, Y and Wu, X and Zhang, X and Wu, H and Yu, W and Ma, M and Ge, Z and Zhang, Y},
title = {Anionic Liposomes as Optimal Membrane Fusion Carriers Enabling in Situ Multiplexed Detection of Extracellular Vesicle MicroRNAs.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e19758},
doi = {10.1002/advs.202519758},
pmid = {41360752},
issn = {2198-3844},
support = {2022YFA1205802//National Key Research and Development Program of China/ ; 2022YFC2406504//National Key Research and Development Program of China/ ; 82572399//National Natural Science Foundation of China/ ; 82302370//National Natural Science Foundation of China/ ; BF2024062//Frontier Technologies R&D Program of Jiangsu/ ; BK20230836//Natural Science Foundation of Jiangsu Province/ ; KYCX24_0471//Postgraduate Research & Practice Innovation Program of Jiangsu Province/ ; CXJH_SEU 25140//SEU Innovation Capability Enhancement Plan for Doctoral Students/ ; },
abstract = {Extracellular vesicle (EV) microRNAs (miRNAs) are promising liquid biopsy biomarkers for non-invasive diagnosis, monitoring, and therapeutic evaluation of cancer. However, sensitive EV miRNA detection is hindered by complex pre-analytical processing. Here, the authors present an anionic liposome (AL) assisted membrane fusion strategy enabling one-step multiplexed quantification of EV miRNAs directly from plasma without EV isolation or RNA extraction, termed EValarm (Anionic Liposome Assisted miRNAs Monitoring for Extracellular Vesicles). Liposomes encapsulating probes are prepared using a microfluidic chip, achieving catalytic signal amplification after target recognition of miRNA. Systematic lipid screening identified ALs as optimal carriers, exhibiting minimal background and superior sensitivity compared to cationic and neutral liposomes. The AL-based assay delivered accuracy comparable to quantitative PCR with a streamlined workflow. Applied to 106 clinical samples from lymphoma patients and healthy controls, integration with artificial intelligence achieved high accuracy (AUC > 0.99). In summary, this study demonstrates a platform enabling direct and sensitive plasma EV miRNA detection, offering strong potential for clinical translation in cancer liquid biopsy.},
}
RevDate: 2025-12-08
The unbearable hardness of inferring being: Comment on "preliminaries to artificial consciousness" by Evers et al.
Physics of life reviews, 56:87-90 pii:S1571-0645(25)00180-0 [Epub ahead of print].
This commentary commends Evers et al.'s multidimensional heuristic for structuring artificial consciousness research while arguing it cannot, as stated, adjudicate the nomological possibility of phenomenal consciousness, which is at stake in current debates. Behavioral-cognitive "profiles" lack a justified principle linking function to experience, and the awareness case study illustrates how externally specified goals can just as well underwrite as-if (pseudo-intentional) control rather than original intentionality. Moreover, the proposed heuristic overlooks that substrate similarity is currently indispensable for justifiably inferring the presence of consciousness beyond the validated case of the adult human brain. Given all this, the framework seems to provide a blueprint for building a more sophisticated philosophical zombie; it does not-and cannot-tell us whether anyone is there.
Additional Links: PMID-41360043
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@article {pmid41360043,
year = {2025},
author = {Chis-Ciure, R},
title = {The unbearable hardness of inferring being: Comment on "preliminaries to artificial consciousness" by Evers et al.},
journal = {Physics of life reviews},
volume = {56},
number = {},
pages = {87-90},
doi = {10.1016/j.plrev.2025.12.004},
pmid = {41360043},
issn = {1873-1457},
abstract = {This commentary commends Evers et al.'s multidimensional heuristic for structuring artificial consciousness research while arguing it cannot, as stated, adjudicate the nomological possibility of phenomenal consciousness, which is at stake in current debates. Behavioral-cognitive "profiles" lack a justified principle linking function to experience, and the awareness case study illustrates how externally specified goals can just as well underwrite as-if (pseudo-intentional) control rather than original intentionality. Moreover, the proposed heuristic overlooks that substrate similarity is currently indispensable for justifiably inferring the presence of consciousness beyond the validated case of the adult human brain. Given all this, the framework seems to provide a blueprint for building a more sophisticated philosophical zombie; it does not-and cannot-tell us whether anyone is there.},
}
RevDate: 2025-12-08
In defense of the double empathy problem hypothesis: An urgently needed alternative to fallacies and injustices in mainstream autism research.
Psychological review pii:2027-00755-001 [Epub ahead of print].
In their theoretical note, "The Double Empathy Problem: A Derivation Chain Analysis and Cautionary Note," Livingston et al. (2024) took a critical look at the double empathy problem hypothesis (DEPH). While they acknowledge that the DEPH offers promising insights, and while their critical note seems, at times, to be written with an eye to furthering and expanding DEPH, the main point they ultimately drive home is that DEPH has a "precarious theoretical and evidence base" and that, given this (allegedly) shaky foundation, applying DEPH "into real-world applications may have unintended and potentially harmful consequences for autistic people and those with similar conditions" (Livingston et al., 2024, p. 10). In this theoretical note, we take a critical look at Livingston et al.'s critique of DEPH, arguing that their warning note is problematic both from an ethical and philosophy of science point of view. (PsycInfo Database Record (c) 2025 APA, all rights reserved).
Additional Links: PMID-41359535
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PubMed:
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@article {pmid41359535,
year = {2025},
author = {Bollen, C and van Grunsven, J},
title = {In defense of the double empathy problem hypothesis: An urgently needed alternative to fallacies and injustices in mainstream autism research.},
journal = {Psychological review},
volume = {},
number = {},
pages = {},
doi = {10.1037/rev0000605},
pmid = {41359535},
issn = {1939-1471},
support = {//Netherlands Organisation for Scientific Research/ ; },
abstract = {In their theoretical note, "The Double Empathy Problem: A Derivation Chain Analysis and Cautionary Note," Livingston et al. (2024) took a critical look at the double empathy problem hypothesis (DEPH). While they acknowledge that the DEPH offers promising insights, and while their critical note seems, at times, to be written with an eye to furthering and expanding DEPH, the main point they ultimately drive home is that DEPH has a "precarious theoretical and evidence base" and that, given this (allegedly) shaky foundation, applying DEPH "into real-world applications may have unintended and potentially harmful consequences for autistic people and those with similar conditions" (Livingston et al., 2024, p. 10). In this theoretical note, we take a critical look at Livingston et al.'s critique of DEPH, arguing that their warning note is problematic both from an ethical and philosophy of science point of view. (PsycInfo Database Record (c) 2025 APA, all rights reserved).},
}
RevDate: 2025-12-08
Exploring the duality of voice habit: Testing and extending theory and measurement.
The Journal of applied psychology pii:2026-99582-001 [Epub ahead of print].
Scholars increasingly recognize the existence of voice habit, wherein employees speak up automatically without considering relevant situational factors, being able to control their impulse to voice, and exerting effort in deciding whether to voice. However, a lack of theory testing and an absence of a psychometrically valid measure have called into question its theoretical usefulness as well as its construct validity. Moreover, contrary to Lam et al.'s (2018) theorizing on the interpersonal costs and intrapersonal benefits of voice habit, research on the reticence bias suggests the opposite: Habitual voicers may gain interpersonal benefits by experiencing higher supervisor liking, but they may also suffer intrapersonal costs by experiencing voice regret. Integrating these divergent insights with theorizing on voice habit, we predict that voice habit may elicit supervisor liking when supervisors perceive habitual voicers as having higher prosocial motives or behavioral integrity, even though habitual voicers may experience regret in work units with a weaker voice climate. Results from a multiwave, multisource field study with 435 employees and 135 supervisors using a 12-item validated scale of voice habit support our hypotheses. Our work provides a direct test and extension of the recently proposed theorizing on voice habit and introduces a psychometrically valid measure for future research use. Our findings also empirically support the dual nature of voice habit, highlighting both its potential functional interpersonal outcomes in relation to supervisors and its potential dysfunctional intrapersonal outcomes for habitual voicers. (PsycInfo Database Record (c) 2025 APA, all rights reserved).
Additional Links: PMID-41359530
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PubMed:
Citation:
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@article {pmid41359530,
year = {2025},
author = {Rees, L and Lam, CF and Du, QS and Yu, A and Wong, MN and Xie, H},
title = {Exploring the duality of voice habit: Testing and extending theory and measurement.},
journal = {The Journal of applied psychology},
volume = {},
number = {},
pages = {},
doi = {10.1037/apl0001326},
pmid = {41359530},
issn = {1939-1854},
support = {//National Natural Science Foundation of China/ ; //Hong Kong General Research Fund/ ; },
abstract = {Scholars increasingly recognize the existence of voice habit, wherein employees speak up automatically without considering relevant situational factors, being able to control their impulse to voice, and exerting effort in deciding whether to voice. However, a lack of theory testing and an absence of a psychometrically valid measure have called into question its theoretical usefulness as well as its construct validity. Moreover, contrary to Lam et al.'s (2018) theorizing on the interpersonal costs and intrapersonal benefits of voice habit, research on the reticence bias suggests the opposite: Habitual voicers may gain interpersonal benefits by experiencing higher supervisor liking, but they may also suffer intrapersonal costs by experiencing voice regret. Integrating these divergent insights with theorizing on voice habit, we predict that voice habit may elicit supervisor liking when supervisors perceive habitual voicers as having higher prosocial motives or behavioral integrity, even though habitual voicers may experience regret in work units with a weaker voice climate. Results from a multiwave, multisource field study with 435 employees and 135 supervisors using a 12-item validated scale of voice habit support our hypotheses. Our work provides a direct test and extension of the recently proposed theorizing on voice habit and introduces a psychometrically valid measure for future research use. Our findings also empirically support the dual nature of voice habit, highlighting both its potential functional interpersonal outcomes in relation to supervisors and its potential dysfunctional intrapersonal outcomes for habitual voicers. (PsycInfo Database Record (c) 2025 APA, all rights reserved).},
}
RevDate: 2025-12-08
Novel and rare variants in amyotrophic lateral sclerosis genes identified in Malaysian patients.
Amyotrophic lateral sclerosis & frontotemporal degeneration [Epub ahead of print].
There is limited information on the genetic architecture of amyotrophic lateral sclerosis (ALS) in Southeast Asian populations. To address this knowledge gap, we performed 1) SOD1 (exon 1-4), FUS (exon 13-15), TARDBP (exon 6) and ATXN2 repeat expansion screening in 201 multi-ethnic Malaysian (Malay, Chinese, Indian and others) ALS patients, 2) C9orf72 repeat expansion testing in 179 subset patients, and 3) a panel of 61 ALS-associated genes screening in 112 subset cases using either whole genome (n = 21) or exome (n = 91) sequencing datasets. Among the patients, the observed mutational frequencies in key ALS genes were: SOD1 3.0% (6/201), C9orf72 2.2% (4/179), ATXN2 2.0% (4/201), FUS 1.5% (3/201), and TARDBP 1.5% (3/201). Of the 112 cases that underwent WGS/WES, 6.3% (7/112) comprised of pathogenic and likely pathogenic variants in FIG4 (p.Lys657Serfs*2), FUS (p.Arg485Profs*32), TARDBP (p.Ile383del), NEK1 (p.Ile633Asnfs*28), GRN (c.599-1G > C), CYP27A1 (p.Met1Thr) and SPAST (p.Glu449Gly). Additionally, 42.9% (48/112) had at least one variant of uncertain significance (VUS) in 34 genes. Notably, in the 24 genes classified as 'definitive' by the ClinGen ALS Spectrum Disorders Gene Curation Expert Panel, five patients (4.5%, 5/112) harbored more than one likely pathogenic variant and/or VUS. However, burden analysis revealed no significant differences in clinical characteristics between patients with varying numbers of variants. Our findings highlight the utility of next-generation sequencing in elucidating the genetic basis of ALS in Malaysian and Southeast Asian ethnic groups, including the identification of several novel variants of clinical interest as well as increasing diagnostic yield up to 47.7%.
Additional Links: PMID-41359433
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PubMed:
Citation:
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@article {pmid41359433,
year = {2025},
author = {Zulhairy-Liong, NA and Edgar, S and Ellis, M and Zhu, D and Lai, K and Capelle, DP and Sabirin, S and Pek, EW and Nair, P and Ang, CM and Kennerson, ML and Shahrizaila, N and Ahmad-Annuar, A},
title = {Novel and rare variants in amyotrophic lateral sclerosis genes identified in Malaysian patients.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/21678421.2025.2582832},
pmid = {41359433},
issn = {2167-9223},
abstract = {There is limited information on the genetic architecture of amyotrophic lateral sclerosis (ALS) in Southeast Asian populations. To address this knowledge gap, we performed 1) SOD1 (exon 1-4), FUS (exon 13-15), TARDBP (exon 6) and ATXN2 repeat expansion screening in 201 multi-ethnic Malaysian (Malay, Chinese, Indian and others) ALS patients, 2) C9orf72 repeat expansion testing in 179 subset patients, and 3) a panel of 61 ALS-associated genes screening in 112 subset cases using either whole genome (n = 21) or exome (n = 91) sequencing datasets. Among the patients, the observed mutational frequencies in key ALS genes were: SOD1 3.0% (6/201), C9orf72 2.2% (4/179), ATXN2 2.0% (4/201), FUS 1.5% (3/201), and TARDBP 1.5% (3/201). Of the 112 cases that underwent WGS/WES, 6.3% (7/112) comprised of pathogenic and likely pathogenic variants in FIG4 (p.Lys657Serfs*2), FUS (p.Arg485Profs*32), TARDBP (p.Ile383del), NEK1 (p.Ile633Asnfs*28), GRN (c.599-1G > C), CYP27A1 (p.Met1Thr) and SPAST (p.Glu449Gly). Additionally, 42.9% (48/112) had at least one variant of uncertain significance (VUS) in 34 genes. Notably, in the 24 genes classified as 'definitive' by the ClinGen ALS Spectrum Disorders Gene Curation Expert Panel, five patients (4.5%, 5/112) harbored more than one likely pathogenic variant and/or VUS. However, burden analysis revealed no significant differences in clinical characteristics between patients with varying numbers of variants. Our findings highlight the utility of next-generation sequencing in elucidating the genetic basis of ALS in Malaysian and Southeast Asian ethnic groups, including the identification of several novel variants of clinical interest as well as increasing diagnostic yield up to 47.7%.},
}
RevDate: 2025-12-08
Scaling and sampling dependencies of forest canopy height mapping towards jurisdictional biomass reporting using airborne LiDAR and small-area estimation.
Carbon balance and management pii:10.1186/s13021-025-00370-9 [Epub ahead of print].
Consolidated airborne laser scanning (ALS) programs, satellite imagery and spaceborne structural measurements have enabled major advances in canopy height mapping that translate towards the forest carbon biomass arena. However, we must carefully evaluate the cost of using fine-grained canopy height products to predict biomass under calibration models scoped at the scale of inventory plots. In this study, we estimated biomass using field plots and ALS metrics before predicting biomass over a jurisdiction of ~ 15,500 km[2] in Spain using 10 m, 25 m, 44 m, and 100 m as prediction scales. We altered the scale of ALS-based biomass predictors in 10 sub-jurisdictions intensively surveyed by the Spanish National Forest Inventory (NFI) before estimating mean and total biomass using three options: (i) traditional NFI design-based (DB) estimation, (ii) a model-based (MB) approach using scale-varying canopy height metrics from ALS and NFI plots, and (iii) an small-area estimation (SAE) implemntation designed for sub-jurisdictional domains. Higher uncertainties - relative standard errors (SE) - were found for DB, particularly at sub-jurisdictional and stratum levels. We observed a consistent increase in uncertainty for MB estimation from the finest 10 m scale up to 100 m. In MB estimation, the maximum relative bias reached 11% for 10-m predictions compared to the baseline estimate at the NFI sampling native resolution. The bias associated with the prediction scale ranged from + 5% (25 m) to -8% (100 m). The mean biomass estimates for SAE generally ranged between DB and MB but at lower uncertainty to the former, especially as the NFI sampling becomes scarcer and not enough for solid inference of biomass mean. The SEA statistics helped to disentangle biomass comparisons between ALS-based inference and the traditional NFI estimation that do not incorporate remote sensing data.
Additional Links: PMID-41359202
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PubMed:
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@article {pmid41359202,
year = {2025},
author = {Guerra-Hernández, J and Mauro-Gutiérrez, F and Rodríguez-Puerta, F and Pascual, A},
title = {Scaling and sampling dependencies of forest canopy height mapping towards jurisdictional biomass reporting using airborne LiDAR and small-area estimation.},
journal = {Carbon balance and management},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13021-025-00370-9},
pmid = {41359202},
issn = {1750-0680},
support = {2023.15225.TENURE.008//Fundação para a Ciência e a Tecnologia/ ; PID2022-140104OA-I00//Spanish Ministry of Science and Innovation/ ; },
abstract = {Consolidated airborne laser scanning (ALS) programs, satellite imagery and spaceborne structural measurements have enabled major advances in canopy height mapping that translate towards the forest carbon biomass arena. However, we must carefully evaluate the cost of using fine-grained canopy height products to predict biomass under calibration models scoped at the scale of inventory plots. In this study, we estimated biomass using field plots and ALS metrics before predicting biomass over a jurisdiction of ~ 15,500 km[2] in Spain using 10 m, 25 m, 44 m, and 100 m as prediction scales. We altered the scale of ALS-based biomass predictors in 10 sub-jurisdictions intensively surveyed by the Spanish National Forest Inventory (NFI) before estimating mean and total biomass using three options: (i) traditional NFI design-based (DB) estimation, (ii) a model-based (MB) approach using scale-varying canopy height metrics from ALS and NFI plots, and (iii) an small-area estimation (SAE) implemntation designed for sub-jurisdictional domains. Higher uncertainties - relative standard errors (SE) - were found for DB, particularly at sub-jurisdictional and stratum levels. We observed a consistent increase in uncertainty for MB estimation from the finest 10 m scale up to 100 m. In MB estimation, the maximum relative bias reached 11% for 10-m predictions compared to the baseline estimate at the NFI sampling native resolution. The bias associated with the prediction scale ranged from + 5% (25 m) to -8% (100 m). The mean biomass estimates for SAE generally ranged between DB and MB but at lower uncertainty to the former, especially as the NFI sampling becomes scarcer and not enough for solid inference of biomass mean. The SEA statistics helped to disentangle biomass comparisons between ALS-based inference and the traditional NFI estimation that do not incorporate remote sensing data.},
}
RevDate: 2025-12-08
Four families with slowly progressive ALS due to p.Val120Leu SOD1 variant in Northeast Brazil.
Amyotrophic lateral sclerosis & frontotemporal degeneration [Epub ahead of print].
Objective: SOD1 mutations are the second most prevalent variants in amyotrophic lateral sclerosis (ALS). Epidemiological data about SOD1 mutations are scarce in Brazil. Here, we report the clinical and genetic findings of four Brazilian families with p.Val120Leu SOD1 variant. Methods: This study is part of an epidemiological study of the prevalence of ALS conducted in the State of Ceará, Brazil. We reviewed the medical records of families with p.Val120Leu (c.358G > C, exon 5) SOD1 variant seen at the Walter Cantídio University Hospital, Federal University of Ceará, Brazil. Results: We identified 15 patients from 4 families with p.Val120Leu SOD1 variant among 251 ALS patients. Of these, six were personally examined and had ALS confirmed and five had confirmatory genetic testing (four homozygous and one heterozygous). C9orf72 testing was normal in the heterozygous patient. In two families, three older heterozygous patients (genetically tested) had no signs or symptoms of ALS. The mean age of symptom onset was 46.7 ± 13.4 years. Features of ALS in the four families were very similar, with prolonged disease duration and upper and lower motor neuron involvement, fulfilling the Revised El Escorial, Awaji, and Gold Coast diagnostic criteria. All examined living patients had limb onset and a few bulbar symptoms. Conclusion: p.Val120Leu SOD1 variant leads to slowly progressive ALS with incomplete penetrance. Our findings are similar to a previous report of ALS due to p.Asp90Ala SOD1 variant.
Additional Links: PMID-41359166
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PubMed:
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@article {pmid41359166,
year = {2025},
author = {Gondim, FAA and Fernandes, JMA and Dutra Junior, AM and Thomas, FP},
title = {Four families with slowly progressive ALS due to p.Val120Leu SOD1 variant in Northeast Brazil.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-5},
doi = {10.1080/21678421.2025.2597943},
pmid = {41359166},
issn = {2167-9223},
abstract = {Objective: SOD1 mutations are the second most prevalent variants in amyotrophic lateral sclerosis (ALS). Epidemiological data about SOD1 mutations are scarce in Brazil. Here, we report the clinical and genetic findings of four Brazilian families with p.Val120Leu SOD1 variant. Methods: This study is part of an epidemiological study of the prevalence of ALS conducted in the State of Ceará, Brazil. We reviewed the medical records of families with p.Val120Leu (c.358G > C, exon 5) SOD1 variant seen at the Walter Cantídio University Hospital, Federal University of Ceará, Brazil. Results: We identified 15 patients from 4 families with p.Val120Leu SOD1 variant among 251 ALS patients. Of these, six were personally examined and had ALS confirmed and five had confirmatory genetic testing (four homozygous and one heterozygous). C9orf72 testing was normal in the heterozygous patient. In two families, three older heterozygous patients (genetically tested) had no signs or symptoms of ALS. The mean age of symptom onset was 46.7 ± 13.4 years. Features of ALS in the four families were very similar, with prolonged disease duration and upper and lower motor neuron involvement, fulfilling the Revised El Escorial, Awaji, and Gold Coast diagnostic criteria. All examined living patients had limb onset and a few bulbar symptoms. Conclusion: p.Val120Leu SOD1 variant leads to slowly progressive ALS with incomplete penetrance. Our findings are similar to a previous report of ALS due to p.Asp90Ala SOD1 variant.},
}
RevDate: 2025-12-08
CmpDate: 2025-12-08
Interpreting fractional flow reserve-guided percutaneous coronary intervention vs coronary artery bypass grafting outcomes.
World journal of cardiology, 17(11):113225.
Kataveni et al's meta-analysis offers an important contemporary synthesis of randomized evidence comparing fractional flow reserve-guided percutaneous coronary intervention and coronary artery bypass grafting (CABG) in multivessel coronary artery disease (CAD). The pooled analysis found no significant difference in all-cause mortality or stroke, yet CABG was superior in reducing myocardial infarction, major adverse cardiac events, and repeat revascularization. These results confirm CABG's durability even in the era of physiological lesion assessment and second-generation drug-eluting stents. From a traditional Chinese medicine (TCM) perspective, multivessel CAD corresponds to syndromes such as "heart vessel obstruction" and "Qi and blood stagnation", in which local blockage is compounded by systemic imbalance. While revascularization addresses the structural impediment to blood flow, TCM approaches, including herbal medicine, acupuncture, and lifestyle therapy, aim to improve microcirculation, reduce inflammation, and support recovery, potentially mitigating recurrent ischemic events. This commentary argues that future research should integrate optimal revascularization strategies with rigorously evaluated TCM interventions to address both the anatomical and systemic dimensions of CAD and improve long-term patient outcomes.
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@article {pmid41356587,
year = {2025},
author = {Liu, HR and Weng, JL},
title = {Interpreting fractional flow reserve-guided percutaneous coronary intervention vs coronary artery bypass grafting outcomes.},
journal = {World journal of cardiology},
volume = {17},
number = {11},
pages = {113225},
pmid = {41356587},
issn = {1949-8462},
abstract = {Kataveni et al's meta-analysis offers an important contemporary synthesis of randomized evidence comparing fractional flow reserve-guided percutaneous coronary intervention and coronary artery bypass grafting (CABG) in multivessel coronary artery disease (CAD). The pooled analysis found no significant difference in all-cause mortality or stroke, yet CABG was superior in reducing myocardial infarction, major adverse cardiac events, and repeat revascularization. These results confirm CABG's durability even in the era of physiological lesion assessment and second-generation drug-eluting stents. From a traditional Chinese medicine (TCM) perspective, multivessel CAD corresponds to syndromes such as "heart vessel obstruction" and "Qi and blood stagnation", in which local blockage is compounded by systemic imbalance. While revascularization addresses the structural impediment to blood flow, TCM approaches, including herbal medicine, acupuncture, and lifestyle therapy, aim to improve microcirculation, reduce inflammation, and support recovery, potentially mitigating recurrent ischemic events. This commentary argues that future research should integrate optimal revascularization strategies with rigorously evaluated TCM interventions to address both the anatomical and systemic dimensions of CAD and improve long-term patient outcomes.},
}
RevDate: 2025-12-08
CmpDate: 2025-12-08
Effect of mobile phone applications on medication adherence among patients with coronary artery diseases: A scoping review.
World journal of cardiology, 17(11):114140.
Patients with cardiovascular disease rely on medication to achieve favorable long-term clinical results. Poor adherence has been linked to a relative increase in mortality of 50%-80% as well as higher health care costs. This scoping review thus aimed to explore the evidence of the effects of mobile health care apps on medication adherence in patients with cardiovascular diseases. A comprehensive data search and extraction was done in line with the updated Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews checklist. A total of 10 studies were included for the review. The mean pooled improvement in adherence was found to be 18% and the most effective tool was the digital therapeutics app discussed in Li et al's study. Smartphones and apps enhance coronary artery disease management by promoting medication compliance. Challenges include data security and smartphone usage among the elderly. Tailored apps or voice assistants offer potential solutions.
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@article {pmid41356579,
year = {2025},
author = {Seyam, MK and Shaik, RA and Miraj, M and Alzahrani, NS and Shaik, AR and Ajmera, P and Kalra, S and Miraj, SA and Shawky, GM and Nurani, KM and A, P},
title = {Effect of mobile phone applications on medication adherence among patients with coronary artery diseases: A scoping review.},
journal = {World journal of cardiology},
volume = {17},
number = {11},
pages = {114140},
pmid = {41356579},
issn = {1949-8462},
abstract = {Patients with cardiovascular disease rely on medication to achieve favorable long-term clinical results. Poor adherence has been linked to a relative increase in mortality of 50%-80% as well as higher health care costs. This scoping review thus aimed to explore the evidence of the effects of mobile health care apps on medication adherence in patients with cardiovascular diseases. A comprehensive data search and extraction was done in line with the updated Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews checklist. A total of 10 studies were included for the review. The mean pooled improvement in adherence was found to be 18% and the most effective tool was the digital therapeutics app discussed in Li et al's study. Smartphones and apps enhance coronary artery disease management by promoting medication compliance. Challenges include data security and smartphone usage among the elderly. Tailored apps or voice assistants offer potential solutions.},
}
RevDate: 2025-12-08
CmpDate: 2025-12-08
Antisense oligonucleotides targeting valosin-containing protein ameliorate muscle pathology and molecular defects in cell and mouse models of multisystem proteinopathy.
Clinical and translational medicine, 15(12):e70530.
BACKGROUND: Valosin-containing protein (VCP) related disease, also known as multisystem proteinopathy 1 (MSP1), is an autosomal dominant disease caused by gain-of-function pathogenic variants of the VCP gene. The disease presents with variable combinations of inclusion body myopathy, early-onset Paget's disease of bone, frontotemporal dementia and may also overlap with familial amyotrophic lateral sclerosis. There is currently no treatment for this progressive disease associated with early demise resulting from proximal limb girdle and respiratory muscle weakness. We hypothesise that regulating VCP hyperactivity to normal levels can reduce the disease pathology.
MAIN TOPICS COVERED: In this study, we assessed the effect of antisense oligonucleotides (ASOs) specifically targeting the human VCP gene in the patient (R155H) iPSC-derived skeletal muscle progenitor cells (SMPCs). ASOs were well tolerated up to a concentration of 5 µM and significantly reduced VCP protein expression in the SMPCs by 48% (95% CI [39-56]). We also treated the transgenic mouse model of VCP disease with the overexpressed humanised VCP severe A232E pathogenic gene variant (VCP A232E mice) with weekly subcutaneous ASO injections starting from 6 months of age for 3 months. In the skeletal muscle of transgenic mice, ASOs resulted in 30% (95% CI [27-32]) knockdown of VCP protein compared with control ASO. The ASO-mediated reduction of VCP expression in muscle tissue was associated with improvement in autophagy flux and reduction in TAR DNA binding protein 43 (TDP-43) expression, hallmarks of VCP related MSP1. In addition, ASO-treated VCP A232E mice showed improvements in functional tests of muscle strength, such as rotarod and inverted screen test compared with mice treated with control ASO.
CONCLUSIONS: These results suggest that targeting VCP could be beneficial in preventing the progression of the VCP myopathy and hold promise for the treatment of patients with VCP related MSP1.
KEY POINTS: VCP multisystem proteinopathy 1 is caused by gain-of-function pathogenic variants of the VCP gene. VCP targeting ASOs were well tolerated and significantly reduced VCP, TAR DNA binding protein 43 (TDP 43), and autophagy protein expression in the (R155H) iPSC-derived skeletal muscle progenitor cells (SMPCs). The ASOs reduced VCP, TDP-43, and autophagy flux expression, and improved functional tests of muscle strength in the humanized VCP A232E mice.
Additional Links: PMID-41355735
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@article {pmid41355735,
year = {2025},
author = {Pal, P and Carrer, M and Weiss, L and Jaime, OG and Cheng, C and Shmara, A and Boock, V and Bosch, D and Youssef, M and Fazeli, Y and Afetian, M and Grossman, TR and Hicks, MR and Jafar-Nejad, P and Kimonis, V},
title = {Antisense oligonucleotides targeting valosin-containing protein ameliorate muscle pathology and molecular defects in cell and mouse models of multisystem proteinopathy.},
journal = {Clinical and translational medicine},
volume = {15},
number = {12},
pages = {e70530},
doi = {10.1002/ctm2.70530},
pmid = {41355735},
issn = {2001-1326},
support = {1297770//Muscular Dystrophy Association/ ; //Cure VCP Disease Inc. Ionis Pharmaceuticals, Inc./ ; },
mesh = {Animals ; *Valosin Containing Protein/genetics/metabolism/antagonists & inhibitors ; Mice ; *Oligonucleotides, Antisense/pharmacology/therapeutic use ; Disease Models, Animal ; Humans ; Muscle, Skeletal/pathology ; Muscular Dystrophies, Limb-Girdle/genetics ; Frontotemporal Dementia/genetics ; Myositis, Inclusion Body ; Osteitis Deformans/genetics ; },
abstract = {BACKGROUND: Valosin-containing protein (VCP) related disease, also known as multisystem proteinopathy 1 (MSP1), is an autosomal dominant disease caused by gain-of-function pathogenic variants of the VCP gene. The disease presents with variable combinations of inclusion body myopathy, early-onset Paget's disease of bone, frontotemporal dementia and may also overlap with familial amyotrophic lateral sclerosis. There is currently no treatment for this progressive disease associated with early demise resulting from proximal limb girdle and respiratory muscle weakness. We hypothesise that regulating VCP hyperactivity to normal levels can reduce the disease pathology.
MAIN TOPICS COVERED: In this study, we assessed the effect of antisense oligonucleotides (ASOs) specifically targeting the human VCP gene in the patient (R155H) iPSC-derived skeletal muscle progenitor cells (SMPCs). ASOs were well tolerated up to a concentration of 5 µM and significantly reduced VCP protein expression in the SMPCs by 48% (95% CI [39-56]). We also treated the transgenic mouse model of VCP disease with the overexpressed humanised VCP severe A232E pathogenic gene variant (VCP A232E mice) with weekly subcutaneous ASO injections starting from 6 months of age for 3 months. In the skeletal muscle of transgenic mice, ASOs resulted in 30% (95% CI [27-32]) knockdown of VCP protein compared with control ASO. The ASO-mediated reduction of VCP expression in muscle tissue was associated with improvement in autophagy flux and reduction in TAR DNA binding protein 43 (TDP-43) expression, hallmarks of VCP related MSP1. In addition, ASO-treated VCP A232E mice showed improvements in functional tests of muscle strength, such as rotarod and inverted screen test compared with mice treated with control ASO.
CONCLUSIONS: These results suggest that targeting VCP could be beneficial in preventing the progression of the VCP myopathy and hold promise for the treatment of patients with VCP related MSP1.
KEY POINTS: VCP multisystem proteinopathy 1 is caused by gain-of-function pathogenic variants of the VCP gene. VCP targeting ASOs were well tolerated and significantly reduced VCP, TAR DNA binding protein 43 (TDP 43), and autophagy protein expression in the (R155H) iPSC-derived skeletal muscle progenitor cells (SMPCs). The ASOs reduced VCP, TDP-43, and autophagy flux expression, and improved functional tests of muscle strength in the humanized VCP A232E mice.},
}
MeSH Terms:
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hide MeSH Terms
Animals
*Valosin Containing Protein/genetics/metabolism/antagonists & inhibitors
Mice
*Oligonucleotides, Antisense/pharmacology/therapeutic use
Disease Models, Animal
Humans
Muscle, Skeletal/pathology
Muscular Dystrophies, Limb-Girdle/genetics
Frontotemporal Dementia/genetics
Myositis, Inclusion Body
Osteitis Deformans/genetics
RevDate: 2025-12-08
CmpDate: 2025-12-08
Does Your Love Lift Me Higher? A Direct Replication of the Energising Role of Secure Relationships.
International journal of psychology : Journal international de psychologie, 61(1):e70144.
Previous work has revealed that priming people with significant others increases feelings of security and energy, and in turn, boosts exploration motivations. In this preregistered study, we directly replicated Luke et al.'s (2012) Study 2 (N = 281). We found similar results as the replicated study regarding increased security feelings and exploration motivations on the self-report measures after the priming. However, we did not find any support for the increased energy feelings after the attachment security priming. In addition, contrary to Luke et al.'s (2012) results, energy feelings did not mediate the relationship between security priming and exploration motivations. A discussion of null findings, along with the limitations of self-reports and potential misinterpretation of the mediational analyses, follows. We also discuss possible future implications of the current findings.
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@article {pmid41355171,
year = {2026},
author = {Lağap, AC and Harma, M},
title = {Does Your Love Lift Me Higher? A Direct Replication of the Energising Role of Secure Relationships.},
journal = {International journal of psychology : Journal international de psychologie},
volume = {61},
number = {1},
pages = {e70144},
doi = {10.1002/ijop.70144},
pmid = {41355171},
issn = {1464-066X},
mesh = {Humans ; Female ; Male ; *Motivation ; *Love ; Adult ; *Object Attachment ; Young Adult ; *Interpersonal Relations ; Adolescent ; },
abstract = {Previous work has revealed that priming people with significant others increases feelings of security and energy, and in turn, boosts exploration motivations. In this preregistered study, we directly replicated Luke et al.'s (2012) Study 2 (N = 281). We found similar results as the replicated study regarding increased security feelings and exploration motivations on the self-report measures after the priming. However, we did not find any support for the increased energy feelings after the attachment security priming. In addition, contrary to Luke et al.'s (2012) results, energy feelings did not mediate the relationship between security priming and exploration motivations. A discussion of null findings, along with the limitations of self-reports and potential misinterpretation of the mediational analyses, follows. We also discuss possible future implications of the current findings.},
}
MeSH Terms:
show MeSH Terms
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Humans
Female
Male
*Motivation
*Love
Adult
*Object Attachment
Young Adult
*Interpersonal Relations
Adolescent
RevDate: 2025-12-08
A Systems-Approach to Addressing the US Rural Veterinarian Shortage Through Collaborative Problem-Solving Training and Education.
New directions for student leadership [Epub ahead of print].
The shortage of rural veterinarians in the United States poses significant challenges to food security, public health, and the agricultural economy. This article explores two systems-based training strategies to address this issue through two case studies: the Integrated Beef Cattle Program (IBCP) in the College of Veterinary Medicine (CVM) at Oklahoma State University (OSU) and the development of adaptive leadership and collaborative problem-solving capacity among rural veterinarians at Pat Dye Clinics. Grounded in Heifetz et al.'s (2009) adaptive leadership framework and Kirton's (2011) Adaption-Innovation Theory (A-I theory), these initiatives demonstrate how leadership development and cognitive diversity can enhance recruitment, retention, and resilience in rural veterinary practice. Findings suggest that integrating leadership learning in veterinary education and professional development can serve as a critical leverage point for systemic change.
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@article {pmid41355168,
year = {2025},
author = {Cline, LL and Biggs, R and Butler, JS and Nichols, C},
title = {A Systems-Approach to Addressing the US Rural Veterinarian Shortage Through Collaborative Problem-Solving Training and Education.},
journal = {New directions for student leadership},
volume = {},
number = {},
pages = {},
doi = {10.1002/yd.70028},
pmid = {41355168},
issn = {2373-3357},
abstract = {The shortage of rural veterinarians in the United States poses significant challenges to food security, public health, and the agricultural economy. This article explores two systems-based training strategies to address this issue through two case studies: the Integrated Beef Cattle Program (IBCP) in the College of Veterinary Medicine (CVM) at Oklahoma State University (OSU) and the development of adaptive leadership and collaborative problem-solving capacity among rural veterinarians at Pat Dye Clinics. Grounded in Heifetz et al.'s (2009) adaptive leadership framework and Kirton's (2011) Adaption-Innovation Theory (A-I theory), these initiatives demonstrate how leadership development and cognitive diversity can enhance recruitment, retention, and resilience in rural veterinary practice. Findings suggest that integrating leadership learning in veterinary education and professional development can serve as a critical leverage point for systemic change.},
}
RevDate: 2025-12-07
Putative mitochondrial components of frontotemporal lobar degeneration: topological correlations between mitochondrial density and atrophy in FTLD/FTD phenotypes.
Journal of neurology, 273(1):11.
BACKGROUND: Frontotemporal lobar degeneration encompasses a spectrum of clinically, radiologically, and molecularly heterogeneous conditions. Clinical phenotypes are defined based on predominant neuropsychological manifestations and the selective involvement of specific brain regions determines the core symptoms, disability profiles, and care needs. While the unique anatomical patterns of cortical and subcortical degeneration along the FTLD/FTD spectrum are well recognised, the molecular basis of this selective vulnerability remains unclear.
METHODS: A large prospective neuroimaging study has been undertaken to explore topological associations between phenotype-specific atrophy patterns and physiological mitochondrial density along the FTLD/FTD spectrum. Patients with behavioural variant FTD (bvFTD), nonfluent variant primary progressive aphasia (nfvPPA), semantic variant primary progressive aphasia (svPPA), C9orf72-positive ALS-FTD, C9orf72-negative ALS-FTD, and a cohort of healthy controls (HC) were included. FTD phenotypes were first contrasted to healthy controls and the resulting voxelwise maps were correlated to physiological mitochondrial density maps.
RESULTS: We have identified voxelwise associations between atrophic change and physiological mitochondrial density. The resulting correlation coefficients over the entire GM mask revealed weak topological associations with r = 0.217 in C9NEG ALS-FTD, r = 0.251 in C9POS ALS-FTD, r = 0.213 in bvFTD, r = 0.182 in nfvPPA, and r = 0.292 in svPPA at p FWE < 0.001. Our region-of-interest analyses revealed moderate-to-strong regional associations between mitochondrial density and focal degenerative change with r values above 0.65 in multiple brain regions in all five FTD subgroups. Brain regions exhibiting the most significant associations between volume loss and mitochondrial density in each FTD subgroup are the very regions that define the core clinical manifestations of the given phenotype.
DISCUSSION: Cortical and subcortical brain regions with high physiological mitochondrial density are particularly vulnerable to neurodegenerative change in FTD. While these anatomical associations do not indicate direct causation, mitochondrial metabolism may represent an important component in the cascade of focal degeneration.
Additional Links: PMID-41354869
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Citation:
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@article {pmid41354869,
year = {2025},
author = {Tahedl, M and Kleinerova, J and McKenna, MC and Siah, WF and Hardiman, O and Hengeveld, JC and Doherty, MA and McLaughlin, RL and Tan, EL and Hutchinson, S and Bede, P},
title = {Putative mitochondrial components of frontotemporal lobar degeneration: topological correlations between mitochondrial density and atrophy in FTLD/FTD phenotypes.},
journal = {Journal of neurology},
volume = {273},
number = {1},
pages = {11},
pmid = {41354869},
issn = {1432-1459},
support = {(HRB EIA-2017-019/HRBI_/Health Research Board/Ireland ; JPND-Cofund-2-2019-1/HRBI_/Health Research Board/Ireland ; SFI SP20/SP/8953/SFI_/Science Foundation Ireland/Ireland ; },
abstract = {BACKGROUND: Frontotemporal lobar degeneration encompasses a spectrum of clinically, radiologically, and molecularly heterogeneous conditions. Clinical phenotypes are defined based on predominant neuropsychological manifestations and the selective involvement of specific brain regions determines the core symptoms, disability profiles, and care needs. While the unique anatomical patterns of cortical and subcortical degeneration along the FTLD/FTD spectrum are well recognised, the molecular basis of this selective vulnerability remains unclear.
METHODS: A large prospective neuroimaging study has been undertaken to explore topological associations between phenotype-specific atrophy patterns and physiological mitochondrial density along the FTLD/FTD spectrum. Patients with behavioural variant FTD (bvFTD), nonfluent variant primary progressive aphasia (nfvPPA), semantic variant primary progressive aphasia (svPPA), C9orf72-positive ALS-FTD, C9orf72-negative ALS-FTD, and a cohort of healthy controls (HC) were included. FTD phenotypes were first contrasted to healthy controls and the resulting voxelwise maps were correlated to physiological mitochondrial density maps.
RESULTS: We have identified voxelwise associations between atrophic change and physiological mitochondrial density. The resulting correlation coefficients over the entire GM mask revealed weak topological associations with r = 0.217 in C9NEG ALS-FTD, r = 0.251 in C9POS ALS-FTD, r = 0.213 in bvFTD, r = 0.182 in nfvPPA, and r = 0.292 in svPPA at p FWE < 0.001. Our region-of-interest analyses revealed moderate-to-strong regional associations between mitochondrial density and focal degenerative change with r values above 0.65 in multiple brain regions in all five FTD subgroups. Brain regions exhibiting the most significant associations between volume loss and mitochondrial density in each FTD subgroup are the very regions that define the core clinical manifestations of the given phenotype.
DISCUSSION: Cortical and subcortical brain regions with high physiological mitochondrial density are particularly vulnerable to neurodegenerative change in FTD. While these anatomical associations do not indicate direct causation, mitochondrial metabolism may represent an important component in the cascade of focal degeneration.},
}
RevDate: 2025-12-07
Differential effects of overexpression of mutant huntingtin and TDP-43 in agouti-related protein neurons in the arcuate nucleus of the hypothalamus in mice.
Acta neuropathologica communications pii:10.1186/s40478-025-02201-x [Epub ahead of print].
The spectrum of frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS) and Huntington disease (HD) are fatal neurodegenerative disorders with no major disease-modifying therapies. Recent work has shown that the hallmark pathological proteins TAR DNA binding protein of 43 kDa (TDP-43) in FTD/ALS and mutant huntingtin (mHTT) in HD may be interlinked. Furthermore, these disorders share early features of altered metabolism and psychiatric symptoms that have been suggested to arise from pathology in the hypothalamus, an important brain region involved in the regulation of metabolism and emotions. Agouti-related protein (AgRP)-expressing neurons localised exclusively to the arcuate nucleus (ARC) of the hypothalamus are key modulators of body weight regulation and food seeking behaviour, and they have recently been implicated in anxiety- and anhedonic-like processes. The aim of this study was to investigate the effects of overexpression of TDP-43 or mHTT in AgRP-expressing neurons on metabolic, behavioral and neuropathological features in mice. Flex-switch adeno associated viral vectors expressing human wild-type TDP-43, mHTT or green fluorescent protein to serve as a control, were injected into male and female AgRP-Cre mice to target the ARC using stereotactic surgery. We demonstrate targeted overexpression of transgenes including formation of mHTT inclusions in the ARC of the hypothalamus. Overexpression of mHTT led to a significant reduction in AgRP fibres in the hypothalamus 21 weeks post-injection, as well as higher food consumption in female mice. Overexpression of TDP-43 did not lead to the development of any metabolic or behavioral phenotypes in the mice. Our data suggest that AgRP neurons in the ARC are protected from the toxic effects resulting from overexpression of TDP-43 whereas they display some sensitivity to mHTT overexpression resulting in mHTT inclusion formation, reduction in AgRP fibers and sex-specific effects on food consumption. Taken together, other hypothalamic neuronal populations may be more important for the development of non-motor features resulting from overexpression of TDP-43 and mHTT in the hypothalamus.
Additional Links: PMID-41354852
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@article {pmid41354852,
year = {2025},
author = {Oraha, J and Wagner, R and Bergh, S and Lee, NJ and Kirik, D and Petersén, Å},
title = {Differential effects of overexpression of mutant huntingtin and TDP-43 in agouti-related protein neurons in the arcuate nucleus of the hypothalamus in mice.},
journal = {Acta neuropathologica communications},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40478-025-02201-x},
pmid = {41354852},
issn = {2051-5960},
abstract = {The spectrum of frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS) and Huntington disease (HD) are fatal neurodegenerative disorders with no major disease-modifying therapies. Recent work has shown that the hallmark pathological proteins TAR DNA binding protein of 43 kDa (TDP-43) in FTD/ALS and mutant huntingtin (mHTT) in HD may be interlinked. Furthermore, these disorders share early features of altered metabolism and psychiatric symptoms that have been suggested to arise from pathology in the hypothalamus, an important brain region involved in the regulation of metabolism and emotions. Agouti-related protein (AgRP)-expressing neurons localised exclusively to the arcuate nucleus (ARC) of the hypothalamus are key modulators of body weight regulation and food seeking behaviour, and they have recently been implicated in anxiety- and anhedonic-like processes. The aim of this study was to investigate the effects of overexpression of TDP-43 or mHTT in AgRP-expressing neurons on metabolic, behavioral and neuropathological features in mice. Flex-switch adeno associated viral vectors expressing human wild-type TDP-43, mHTT or green fluorescent protein to serve as a control, were injected into male and female AgRP-Cre mice to target the ARC using stereotactic surgery. We demonstrate targeted overexpression of transgenes including formation of mHTT inclusions in the ARC of the hypothalamus. Overexpression of mHTT led to a significant reduction in AgRP fibres in the hypothalamus 21 weeks post-injection, as well as higher food consumption in female mice. Overexpression of TDP-43 did not lead to the development of any metabolic or behavioral phenotypes in the mice. Our data suggest that AgRP neurons in the ARC are protected from the toxic effects resulting from overexpression of TDP-43 whereas they display some sensitivity to mHTT overexpression resulting in mHTT inclusion formation, reduction in AgRP fibers and sex-specific effects on food consumption. Taken together, other hypothalamic neuronal populations may be more important for the development of non-motor features resulting from overexpression of TDP-43 and mHTT in the hypothalamus.},
}
RevDate: 2025-12-07
Revisiting oligodendrocytes in amyotrophic lateral sclerosis using human multicellular stem cell models.
Trends in cell biology pii:S0962-8924(25)00251-X [Epub ahead of print].
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron degeneration, muscle wasting, and eventual paralysis. The clinical and genetic complexity along with rapid disease progression has hindered efforts to model the disease and develop effective treatments. Rodent models and human tissue studies point to dysfunction in oligodendrocyte lineage cells early in disease, although the underlying mechanisms remain unclear. Advances in stem cell research have introduced novel platforms to investigate cells in the oligodendrocyte lineage and their interactions with neurons and other glial cells in complex human genetic backgrounds. This Review summarizes the literature implicating oligodendrocyte lineage cells in ALS and discusses both the potential and limitations of in vitro-derived cultures to shed light on their vulnerabilities and cellular interactions.
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@article {pmid41354564,
year = {2025},
author = {Mouhi, S and Pio, T and Andersen, J},
title = {Revisiting oligodendrocytes in amyotrophic lateral sclerosis using human multicellular stem cell models.},
journal = {Trends in cell biology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tcb.2025.11.003},
pmid = {41354564},
issn = {1879-3088},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron degeneration, muscle wasting, and eventual paralysis. The clinical and genetic complexity along with rapid disease progression has hindered efforts to model the disease and develop effective treatments. Rodent models and human tissue studies point to dysfunction in oligodendrocyte lineage cells early in disease, although the underlying mechanisms remain unclear. Advances in stem cell research have introduced novel platforms to investigate cells in the oligodendrocyte lineage and their interactions with neurons and other glial cells in complex human genetic backgrounds. This Review summarizes the literature implicating oligodendrocyte lineage cells in ALS and discusses both the potential and limitations of in vitro-derived cultures to shed light on their vulnerabilities and cellular interactions.},
}
RevDate: 2025-12-07
Respiratory Strength Training for Patients with Amyotrophic Lateral Sclerosis: A Meta-analysis of Randomized Controlled Trials.
Respiratory medicine pii:S0954-6111(25)00623-7 [Epub ahead of print].
INTRODUCTION: Respiratory strength training (RST) has been considered as a possible add-on treatment for amyotrophic lateral sclerosis (ALS). However, the benefits of RST are still controversial. We performed a meta-analysis of randomized controlled trials (RCTs) on the efficacy of RST in patients with ALS.
METHODS: PubMed, Embase and Cochrane Central were searched for RCTs comparing the use of RST with sham therapy or minimal device load in patients with ALS. The main outcomes were maximal expiratory pressure (MEP), maximal inspiratory pressure (MIP) and the ALS functioning rating scale (ALSFRS-R) score. Statistical analysis was performed using R software and heterogeneity was assessed with I[2] statistics.
RESULTS: Four RCTs were included with a total of 138 patients. RST was used to treat 69 (50%) patients. The mean age was 60.2 ± 10.4 years, with 82 (62.3%) male patients. Follow-up ranged from 2 to 8 months. Subgroup analysis of expiratory muscle training protocols showed a statistically significant improvement in MEP (MD 20.22 cmH2O; 95% CI 2.66-37.77; p=0.04). In overall analyses, there was no difference between groups regarding MEP (MD 9.40 cmH2O; 95% CI -11.57-30.37; p=0.25), MIP (MD 3.26 cmH2O; 95% CI -9.23-15.75; p=0.38), FVC (MD 4.05 %predicted; 95% CI -0.91-9.01; p=0.08) and ALSFRS-R score (MD 0.01 points; 95% CI -0.29-0.32; p=0.85).
CONCLUSION: In this meta-analysis of RCTs including patients with ALS, expiratory muscle training was associated with increased MEP compared with sham or minimal load. However, no statistically significant associations were found for overall RST in MIP, FVC, MEP, and ALSFRS-R.
Additional Links: PMID-41354105
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@article {pmid41354105,
year = {2025},
author = {Araújo, L and Chianca, T and Persaud, C and Hartung, P and Soares, Y and Almirón, G and João, R},
title = {Respiratory Strength Training for Patients with Amyotrophic Lateral Sclerosis: A Meta-analysis of Randomized Controlled Trials.},
journal = {Respiratory medicine},
volume = {},
number = {},
pages = {108560},
doi = {10.1016/j.rmed.2025.108560},
pmid = {41354105},
issn = {1532-3064},
abstract = {INTRODUCTION: Respiratory strength training (RST) has been considered as a possible add-on treatment for amyotrophic lateral sclerosis (ALS). However, the benefits of RST are still controversial. We performed a meta-analysis of randomized controlled trials (RCTs) on the efficacy of RST in patients with ALS.
METHODS: PubMed, Embase and Cochrane Central were searched for RCTs comparing the use of RST with sham therapy or minimal device load in patients with ALS. The main outcomes were maximal expiratory pressure (MEP), maximal inspiratory pressure (MIP) and the ALS functioning rating scale (ALSFRS-R) score. Statistical analysis was performed using R software and heterogeneity was assessed with I[2] statistics.
RESULTS: Four RCTs were included with a total of 138 patients. RST was used to treat 69 (50%) patients. The mean age was 60.2 ± 10.4 years, with 82 (62.3%) male patients. Follow-up ranged from 2 to 8 months. Subgroup analysis of expiratory muscle training protocols showed a statistically significant improvement in MEP (MD 20.22 cmH2O; 95% CI 2.66-37.77; p=0.04). In overall analyses, there was no difference between groups regarding MEP (MD 9.40 cmH2O; 95% CI -11.57-30.37; p=0.25), MIP (MD 3.26 cmH2O; 95% CI -9.23-15.75; p=0.38), FVC (MD 4.05 %predicted; 95% CI -0.91-9.01; p=0.08) and ALSFRS-R score (MD 0.01 points; 95% CI -0.29-0.32; p=0.85).
CONCLUSION: In this meta-analysis of RCTs including patients with ALS, expiratory muscle training was associated with increased MEP compared with sham or minimal load. However, no statistically significant associations were found for overall RST in MIP, FVC, MEP, and ALSFRS-R.},
}
RevDate: 2025-12-07
Reply to Satapathy et al.'s comment on "Dual cross-sectional and longitudinal perspective on the continuum of HIV care to disentangle natural epidemic evolution from real progress, Belgium 2014-2022".
Additional Links: PMID-41353609
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@article {pmid41353609,
year = {2025},
author = {Van Beckhoven, D and Serrien, B and Demeester, R and Van Praet, J and Messiaen, P and Darcis, G and Henrard, S and De Munter, P and Libois, A and Deblonde, J},
title = {Reply to Satapathy et al.'s comment on "Dual cross-sectional and longitudinal perspective on the continuum of HIV care to disentangle natural epidemic evolution from real progress, Belgium 2014-2022".},
journal = {HIV medicine},
volume = {},
number = {},
pages = {},
doi = {10.1111/hiv.70163},
pmid = {41353609},
issn = {1468-1293},
}
RevDate: 2025-12-06
CmpDate: 2025-12-06
GC-orbitrap-HRMS with ROIMCR and MSident targeted and non-targeted analysis of persistent organic pollutants in fish-based certified reference materials.
Analytica chimica acta, 1383:344892.
The use of fish-based reference materials allows the validation of analytical methods used for the monitoring of persistent organic pollutants (POPs) in environmental samples. Thus, the aim of this work has been to apply and validate the Regions of Interest Multivariate Curve Resolution (ROIMCR) procedure, in a first instance, to quantify POPs using two fish-based certified reference materials (CRM) provided by the Institute of Reference Materials (IRMM); and also to identify, with the MSident program, the presence of more POPs in the same samples. Samples were extracted and analyzed by gas chromatography coupled to an Orbitrap mass spectrometer (GC-HRMS). A targeted analysis was performed to quantify the four certified POPs: hexachlorobenzene (HCBz) and hexachlorobutadiene (HCBu) in ERM®-CE100 and pentachlorobenzene (PeCB) and α, β, γ, and δ-hexachlorocyclohexane (HCH) in ERM®-CE103. Quantitative estimations obtained with ROIMCR method were compared with those obtained using the instrument vendor's Xcalibur software. Two tailed t-tests were performed and good agreement was observed between the two approaches and with the certified values. A non-targeted analysis approach was then performed to characterize other unknown POPs present in the samples. Data processed with the ROIMCR method in the non-targeted acquisition mode was complemented with the MSident chemical identification procedure, which allowed the annotation of several polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides (OCPs), phthalates, and polychlorinated biphenyls (PCBs). The presence of some of these compounds was confirmed with the analysis of validation standard mixture samples containing 43 POPs. The ROIMCR methodology herein proposed allows, in a first instance, the quantitative analysis of multiple unknown contaminants present in the analyzed fish-based certified samples by using GC-HRMS data and also, combined with the MSident program, enables a qualitative analysis which could provide a comprehensive assessment of POP pollution patterns in fish or other environmental samples.
Additional Links: PMID-41352930
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@article {pmid41352930,
year = {2026},
author = {Queral-Beltran, A and Lacorte, S and Tauler, R},
title = {GC-orbitrap-HRMS with ROIMCR and MSident targeted and non-targeted analysis of persistent organic pollutants in fish-based certified reference materials.},
journal = {Analytica chimica acta},
volume = {1383},
number = {},
pages = {344892},
doi = {10.1016/j.aca.2025.344892},
pmid = {41352930},
issn = {1873-4324},
mesh = {Animals ; *Gas Chromatography-Mass Spectrometry/standards/methods ; *Fishes ; *Persistent Organic Pollutants ; Reference Standards ; },
abstract = {The use of fish-based reference materials allows the validation of analytical methods used for the monitoring of persistent organic pollutants (POPs) in environmental samples. Thus, the aim of this work has been to apply and validate the Regions of Interest Multivariate Curve Resolution (ROIMCR) procedure, in a first instance, to quantify POPs using two fish-based certified reference materials (CRM) provided by the Institute of Reference Materials (IRMM); and also to identify, with the MSident program, the presence of more POPs in the same samples. Samples were extracted and analyzed by gas chromatography coupled to an Orbitrap mass spectrometer (GC-HRMS). A targeted analysis was performed to quantify the four certified POPs: hexachlorobenzene (HCBz) and hexachlorobutadiene (HCBu) in ERM®-CE100 and pentachlorobenzene (PeCB) and α, β, γ, and δ-hexachlorocyclohexane (HCH) in ERM®-CE103. Quantitative estimations obtained with ROIMCR method were compared with those obtained using the instrument vendor's Xcalibur software. Two tailed t-tests were performed and good agreement was observed between the two approaches and with the certified values. A non-targeted analysis approach was then performed to characterize other unknown POPs present in the samples. Data processed with the ROIMCR method in the non-targeted acquisition mode was complemented with the MSident chemical identification procedure, which allowed the annotation of several polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides (OCPs), phthalates, and polychlorinated biphenyls (PCBs). The presence of some of these compounds was confirmed with the analysis of validation standard mixture samples containing 43 POPs. The ROIMCR methodology herein proposed allows, in a first instance, the quantitative analysis of multiple unknown contaminants present in the analyzed fish-based certified samples by using GC-HRMS data and also, combined with the MSident program, enables a qualitative analysis which could provide a comprehensive assessment of POP pollution patterns in fish or other environmental samples.},
}
MeSH Terms:
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Animals
*Gas Chromatography-Mass Spectrometry/standards/methods
*Fishes
*Persistent Organic Pollutants
Reference Standards
RevDate: 2025-12-06
Response to Maas et al., "Response to Vaz de Faria et al's "Forehead atrophy in frontal fibrosing alopecia: An ultrasonographic and histopathological study of 10 patients".
Additional Links: PMID-41352717
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@article {pmid41352717,
year = {2025},
author = {Doche, I and Vaz de Faria, JR},
title = {Response to Maas et al., "Response to Vaz de Faria et al's "Forehead atrophy in frontal fibrosing alopecia: An ultrasonographic and histopathological study of 10 patients".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.12.015},
pmid = {41352717},
issn = {1097-6787},
}
RevDate: 2025-12-06
Response to Vaz de Faria et al's ''Forehead atrophy in frontal fibrosing alopecia: An ultrasonographic and histopathological study of 10 patients".
Additional Links: PMID-41352714
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@article {pmid41352714,
year = {2025},
author = {Maas, D and Spindler, A and Zappi, I and Shapiro, J and Lo Sicco, KI},
title = {Response to Vaz de Faria et al's ''Forehead atrophy in frontal fibrosing alopecia: An ultrasonographic and histopathological study of 10 patients".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.10.159},
pmid = {41352714},
issn = {1097-6787},
}
RevDate: 2025-12-06
The TDP-43[I383V] heterozygous mutation results in increased TDP-43 expression and altered neuronal activity in ALS patient-derived iPSC motor neurons.
Neuroscience research pii:S0168-0102(25)00186-5 [Epub ahead of print].
TAR-binding protein 43 (TDP-43) is a pathogenic RNA-binding protein associated with amyotrophic lateral sclerosis (ALS). To elucidate the pathogenesis of ALS, we generated induced pluripotent stem cells (iPSCs) from lymphoblastoid cell line (LCL) cells of an ALS patient with the TDP-43[I383V] heterozygous mutation. Furthermore, we generated isogenic wild-type iPSCs from wild-type LCL cells using scarless genome editing with CRISPR/Cas9. A modified iPSC-derived motor neuron culture method utilizing BrainPhys neuronal medium and rat astrocyte co-culture effectively promoted and maintained neuronal activity. Under these conditions, the TDP-43[I383V] heterozygous mutation resulted in increased TDP-43 protein expression through prolonged stabilization. Moreover, mutant iPSC-derived motor neurons showed increased numbers of pre-synapses and altered neuronal activity. These results suggest that the modified motor neuron culture method can help elucidate abnormalities in TDP-43 expression, synapse formation, and neuronal activity caused by the heterozygous TDP-43[I383V] mutation. The model developed in this study has the potential to facilitate the analysis of the early pathological phenotype of ALS.
Additional Links: PMID-41352688
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@article {pmid41352688,
year = {2025},
author = {Chikuchi, R and Kato, Y and Tomatsu, A and Nishisaki, S and Kawakami, Y and Yoshimura, T and Li, J and Iguchi, Y and Onodera, K and Hashimoto, R and Aiba, I and Nakamura, R and Tohnai, G and Atsuta, N and Sobue, G and Okada, Y and Katsuno, M and Yokoi, S},
title = {The TDP-43[I383V] heterozygous mutation results in increased TDP-43 expression and altered neuronal activity in ALS patient-derived iPSC motor neurons.},
journal = {Neuroscience research},
volume = {},
number = {},
pages = {105003},
doi = {10.1016/j.neures.2025.105003},
pmid = {41352688},
issn = {1872-8111},
abstract = {TAR-binding protein 43 (TDP-43) is a pathogenic RNA-binding protein associated with amyotrophic lateral sclerosis (ALS). To elucidate the pathogenesis of ALS, we generated induced pluripotent stem cells (iPSCs) from lymphoblastoid cell line (LCL) cells of an ALS patient with the TDP-43[I383V] heterozygous mutation. Furthermore, we generated isogenic wild-type iPSCs from wild-type LCL cells using scarless genome editing with CRISPR/Cas9. A modified iPSC-derived motor neuron culture method utilizing BrainPhys neuronal medium and rat astrocyte co-culture effectively promoted and maintained neuronal activity. Under these conditions, the TDP-43[I383V] heterozygous mutation resulted in increased TDP-43 protein expression through prolonged stabilization. Moreover, mutant iPSC-derived motor neurons showed increased numbers of pre-synapses and altered neuronal activity. These results suggest that the modified motor neuron culture method can help elucidate abnormalities in TDP-43 expression, synapse formation, and neuronal activity caused by the heterozygous TDP-43[I383V] mutation. The model developed in this study has the potential to facilitate the analysis of the early pathological phenotype of ALS.},
}
RevDate: 2025-12-06
The roles of human endogenous retrovirus in neurodegenerative diseases: A systematic review.
Brain, behavior, and immunity pii:S0889-1591(25)00443-X [Epub ahead of print].
BACKGROUND: Human endogenous retroviruses (HERVs) constitute ∼8 % of the human genome, far exceeding the 2 % occupied by protein-coding genes. Although most HERV sequences are inactive, some HERV elements can be reactivated under certain conditions and may contribute to neurodegenerative diseases (NDDs). However, the findings vary across different HERV families, disease models, and detection methods. Here, we systematically review and synthesize the available evidence on the role of HERVs in human NDDs and reconcile inconsistencies in the literature.
METHODS: We systematically searched MEDLINE, EMBASE, Cochrane Library, PsycINFO, Scopus, Web of Science, CINAHL, and Emcare to identify relevant studies. Two independent reviewers screened studies, assessed quality, and extracted data. Qualitative synthesis was conducted for all included NDDs, specifically Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Parkinson's disease (PD), and due to data availability, meta-analysis was used to assess the impact of HERVs antibodies on ALS only.
RESULTS: Twenty-six studies (N ranges: 6-485) met the inclusion criteria, with majority focusing on HERV-K and ALS. Across studies, the association between HERV expression and NDDs was inconsistent, particularly for ALS, PD, and FTD, whereas investigations in AD showed a more consistent upregulation of specific HERVs. Studies relying on polymerase chain reaction (PCR) (typically smaller) showed inconsistent associations (21 studies), while RNA sequencing studies reported consistent associations (9 studies). A preliminary meta-analysis revealed a fivefold increase [OR: 5.83; 95 % CI: 4.14, 8.18] in ALS risk among participants with positive HERV antibodies.
CONCLUSIONS: The inconsistencies in HERV involvement across NDDs highlight the need for further studies employing standardized methodologies. RNAseq findings on the association of HERVs expression on NDDs support the need for large-scale RNA sequencing studies (rather than small, PCR studies) and careful tissue selection to clarify HERVs' role in NDDs. The association of HERV-K antibodies with ALS risk and prognosis suggests a significant role in disease, which could help detect biomarkers and used as a target for treatment.
Additional Links: PMID-41352634
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PubMed:
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@article {pmid41352634,
year = {2025},
author = {Geleta, LA and Doyle, C and Garton, FC and Fowler, M and Carr, JM and Akkari, PA and McRae, AF and Rogers, ML and Madakkatel, I and Benyamin, B},
title = {The roles of human endogenous retrovirus in neurodegenerative diseases: A systematic review.},
journal = {Brain, behavior, and immunity},
volume = {},
number = {},
pages = {106201},
doi = {10.1016/j.bbi.2025.106201},
pmid = {41352634},
issn = {1090-2139},
abstract = {BACKGROUND: Human endogenous retroviruses (HERVs) constitute ∼8 % of the human genome, far exceeding the 2 % occupied by protein-coding genes. Although most HERV sequences are inactive, some HERV elements can be reactivated under certain conditions and may contribute to neurodegenerative diseases (NDDs). However, the findings vary across different HERV families, disease models, and detection methods. Here, we systematically review and synthesize the available evidence on the role of HERVs in human NDDs and reconcile inconsistencies in the literature.
METHODS: We systematically searched MEDLINE, EMBASE, Cochrane Library, PsycINFO, Scopus, Web of Science, CINAHL, and Emcare to identify relevant studies. Two independent reviewers screened studies, assessed quality, and extracted data. Qualitative synthesis was conducted for all included NDDs, specifically Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Parkinson's disease (PD), and due to data availability, meta-analysis was used to assess the impact of HERVs antibodies on ALS only.
RESULTS: Twenty-six studies (N ranges: 6-485) met the inclusion criteria, with majority focusing on HERV-K and ALS. Across studies, the association between HERV expression and NDDs was inconsistent, particularly for ALS, PD, and FTD, whereas investigations in AD showed a more consistent upregulation of specific HERVs. Studies relying on polymerase chain reaction (PCR) (typically smaller) showed inconsistent associations (21 studies), while RNA sequencing studies reported consistent associations (9 studies). A preliminary meta-analysis revealed a fivefold increase [OR: 5.83; 95 % CI: 4.14, 8.18] in ALS risk among participants with positive HERV antibodies.
CONCLUSIONS: The inconsistencies in HERV involvement across NDDs highlight the need for further studies employing standardized methodologies. RNAseq findings on the association of HERVs expression on NDDs support the need for large-scale RNA sequencing studies (rather than small, PCR studies) and careful tissue selection to clarify HERVs' role in NDDs. The association of HERV-K antibodies with ALS risk and prognosis suggests a significant role in disease, which could help detect biomarkers and used as a target for treatment.},
}
RevDate: 2025-12-06
CmpDate: 2025-12-06
Navigating the Autophagy Maze: ATG and Their Impact on Neurodegenerative Diseases.
Molecular neurobiology, 63(1):260.
Autophagy, a tightly regulated process essential for maintaining cellular homeostasis, plays a critical role in the pathogenesis and progression of neurodegenerative diseases (NDs). These disorders-marked by diverse mechanisms and clinical heterogeneity-pose significant challenges in developing effective therapies. Central to the autophagic machinery are autophagy-related genes (ATGs), whose functions and variants are increasingly recognized as pivotal in modulating disease-specific pathways. This review explores the intricate roles of ATGs in NDs, emphasizing the need for a comprehensive understanding of molecular signaling networks, protein-protein interactions, and regulatory checkpoints that may serve as therapeutic targets. We highlight recent advancements in disease modeling, autophagy assays, and biomarker identification that facilitate the translation of ATG-related discoveries into clinical practice. Furthermore, we underscore the importance of interdisciplinary collaboration across academia, industry, clinical medicine, and regulatory bodies to harness the therapeutic potential of autophagy. This article aims to serve as a detailed roadmap for understanding the role of ATGs in NDs and to illuminate promising avenues for future research and therapeutic development.
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@article {pmid41351663,
year = {2025},
author = {Amirian, R and Merati, A and Babamohamadi, M and Mirahmadi, Y and Esfahani, ML and Rahmani, S and Izadi, Z and Rezazadeh, D},
title = {Navigating the Autophagy Maze: ATG and Their Impact on Neurodegenerative Diseases.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {260},
pmid = {41351663},
issn = {1559-1182},
mesh = {*Autophagy/genetics/physiology ; Humans ; *Neurodegenerative Diseases/genetics/metabolism/pathology ; Animals ; *Autophagy-Related Proteins/metabolism/genetics ; Signal Transduction ; },
abstract = {Autophagy, a tightly regulated process essential for maintaining cellular homeostasis, plays a critical role in the pathogenesis and progression of neurodegenerative diseases (NDs). These disorders-marked by diverse mechanisms and clinical heterogeneity-pose significant challenges in developing effective therapies. Central to the autophagic machinery are autophagy-related genes (ATGs), whose functions and variants are increasingly recognized as pivotal in modulating disease-specific pathways. This review explores the intricate roles of ATGs in NDs, emphasizing the need for a comprehensive understanding of molecular signaling networks, protein-protein interactions, and regulatory checkpoints that may serve as therapeutic targets. We highlight recent advancements in disease modeling, autophagy assays, and biomarker identification that facilitate the translation of ATG-related discoveries into clinical practice. Furthermore, we underscore the importance of interdisciplinary collaboration across academia, industry, clinical medicine, and regulatory bodies to harness the therapeutic potential of autophagy. This article aims to serve as a detailed roadmap for understanding the role of ATGs in NDs and to illuminate promising avenues for future research and therapeutic development.},
}
MeSH Terms:
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*Autophagy/genetics/physiology
Humans
*Neurodegenerative Diseases/genetics/metabolism/pathology
Animals
*Autophagy-Related Proteins/metabolism/genetics
Signal Transduction
RevDate: 2025-12-05
A genome-wide association study identifies the GPM6A locus associated with age at onset in ALS.
Communications biology, 8(1):1720.
Amyotrophic lateral sclerosis (ALS) exhibits considerable clinical variability, such as differences in age at onset (AAO). Multiple factors, including genetic factors, may underlie this variability; however, the specific determinants remain unclear. To identify genes affecting AAO, we have conducted a genome-wide association study in Japanese patients with ALS (discovery cohort: n = 1808; replication cohort: n = 207). Here, we show that the minor A allele of rs113161727 at the ADAM29-GPM6A locus is associated with a younger AAO in the discovery cohort (effect, -4.27 years; p = 4.60 × 10[-8]); this finding has been confirmed in the replication cohort (p = 0.0068) and meta-analysis (p = 1.08 × 10[-9]). Among 65 ALS patients with a SOD1 mutation, the AAO has been found to be 10.2 years younger in those with the A allele than in those without it (p = 0.002). This variant correlates with GPM6A upregulation in iPSC-derived motor neurons, suggesting GPM6A as a candidate AAO modifier. Overall, our study highlights the impact of genetic modifiers on ALS heterogeneity and provides a potential target for delaying disease onset.
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@article {pmid41350806,
year = {2025},
author = {Nakamura, R and Tohnai, G and Atsuta, N and Matsuda, Y and Morimoto, S and Ito, D and Katsuno, M and Izumi, Y and Morita, M and Iwata, I and Yabe, I and Nakazato, T and Hattori, N and Hirayama, T and Kano, O and Tamura, A and Suzuki, N and Aoki, M and Shibuya, K and Kuwabara, S and Oda, M and Hashimoto, R and Aiba, I and Ishihara, T and Onodera, O and Yamashita, T and Ishiura, H and Bokuda, K and Shimizu, T and Ikeda, Y and Hasegawa, K and Tanaka, F and Yokota, T and Kanai, K and Noto, YI and Kaji, R and Watanabe, H and Konishi, T and Hasegawa, M and Fukaya, H and Niwa, JI and Doyu, M and Okada, Y and Nakamura, S and Ozawa, F and Okano, H and Nakatochi, M and Sobue, G and , },
title = {A genome-wide association study identifies the GPM6A locus associated with age at onset in ALS.},
journal = {Communications biology},
volume = {8},
number = {1},
pages = {1720},
pmid = {41350806},
issn = {2399-3642},
support = {23FC0201//Ministry of Health, Labour and Welfare (Ministry of Health, Labour and Welfare, Japan)/ ; JP23ek0109492, JP23ak0101111, JP23ak0101124, JP24wm0425009//Japan Agency for Medical Research and Development (AMED)/ ; JP24ak0101216, JP24ak0101222, JP25wn0625519, JP25ak0101216, JP25ak0101222, JP25ek0109617//Japan Agency for Medical Research and Development (AMED)/ ; JP23ek0109538//Japan Agency for Medical Research and Development (AMED)/ ; JP23bm1123046, JP23kk0305024, JP23bm1423002//Japan Agency for Medical Research and Development (AMED)/ ; JP24bm1423003//Japan Agency for Medical Research and Development (AMED)/ ; JP23bm1123046, JP23kk0305024, JP23bm1423002//Japan Agency for Medical Research and Development (AMED)/ ; JP19km0405216//Japan Agency for Medical Research and Development (AMED)/ ; 19K07973//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 22K07359//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 22K07509//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 19K06523//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 22K07359//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 19K07973//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 22K07509//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 23K06835//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 22K07359//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 22K07509//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 25K10781//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 21H05278//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 19K06523//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 23K06975//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 22H02988//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 23K06975//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 23K24249//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 21H05278//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 16H06277//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 22H04923//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; 22H03350//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) exhibits considerable clinical variability, such as differences in age at onset (AAO). Multiple factors, including genetic factors, may underlie this variability; however, the specific determinants remain unclear. To identify genes affecting AAO, we have conducted a genome-wide association study in Japanese patients with ALS (discovery cohort: n = 1808; replication cohort: n = 207). Here, we show that the minor A allele of rs113161727 at the ADAM29-GPM6A locus is associated with a younger AAO in the discovery cohort (effect, -4.27 years; p = 4.60 × 10[-8]); this finding has been confirmed in the replication cohort (p = 0.0068) and meta-analysis (p = 1.08 × 10[-9]). Among 65 ALS patients with a SOD1 mutation, the AAO has been found to be 10.2 years younger in those with the A allele than in those without it (p = 0.002). This variant correlates with GPM6A upregulation in iPSC-derived motor neurons, suggesting GPM6A as a candidate AAO modifier. Overall, our study highlights the impact of genetic modifiers on ALS heterogeneity and provides a potential target for delaying disease onset.},
}
RevDate: 2025-12-05
Structural mechanisms and insights on multiple nanobodies binding diverse SOD1 epitopes.
Communications biology pii:10.1038/s42003-025-09293-0 [Epub ahead of print].
Copper/zinc superoxide dismutase (SOD1) is a crucial metalloenzyme that mitigates oxidative stress by scavenging superoxide anion radicals. Mutations and aggregation of SOD1 are closely linked to the pathogenesis of amyotrophic lateral sclerosis (ALS). Targeting pathogenic SOD1 with nanobodies presents a promising therapeutic approach. We report the first high-resolution crystal structures of SOD1 in complex with three distinct nanobodies (Nb1, Nb2, and Nb3) and their multimeric assemblies (1:2 and 1:3 stoichiometries), revealing distinct binding epitopes primarily mediated by their complementarity determining regions (CDRs) through hydrogen bonds, salt bridges, and hydrophobic interactions. Structural and biophysical analyses using isothermal titration calorimetry (ITC) and fluorescence-detection size-exclusion chromatography (FSEC) demonstrated that all three nanobodies bind SOD1 simultaneously with nanomolar affinities (KD values ranging from 23.2 nM to 529 nM). Notably, engineered multimeric tandem nanobodies (Nb1-Nb2-Nb3) achieved higher affinity (KD = 4.39 nM) compared to single nanobodies, as validated by ITC. Characterization via dynamic light scattering (DLS) further revealed colloidal stability of SOD1-nanobody complexes. These results provide the first atomic-resolution insights into multi-nanobody targeting of SOD1 without steric interference, establishing a foundation for developing high-affinity tools to detect and manipulate SOD1 in ALS and related neurodegenerative diseases.
Additional Links: PMID-41350409
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@article {pmid41350409,
year = {2025},
author = {Cheng, S and Zhong, C and Zhu, H and Mu, K and Jiang, H and Zhong, P and Ma, Z and Liu, X and Wang, Z and Liu, R and Ding, Y},
title = {Structural mechanisms and insights on multiple nanobodies binding diverse SOD1 epitopes.},
journal = {Communications biology},
volume = {},
number = {},
pages = {},
doi = {10.1038/s42003-025-09293-0},
pmid = {41350409},
issn = {2399-3642},
abstract = {Copper/zinc superoxide dismutase (SOD1) is a crucial metalloenzyme that mitigates oxidative stress by scavenging superoxide anion radicals. Mutations and aggregation of SOD1 are closely linked to the pathogenesis of amyotrophic lateral sclerosis (ALS). Targeting pathogenic SOD1 with nanobodies presents a promising therapeutic approach. We report the first high-resolution crystal structures of SOD1 in complex with three distinct nanobodies (Nb1, Nb2, and Nb3) and their multimeric assemblies (1:2 and 1:3 stoichiometries), revealing distinct binding epitopes primarily mediated by their complementarity determining regions (CDRs) through hydrogen bonds, salt bridges, and hydrophobic interactions. Structural and biophysical analyses using isothermal titration calorimetry (ITC) and fluorescence-detection size-exclusion chromatography (FSEC) demonstrated that all three nanobodies bind SOD1 simultaneously with nanomolar affinities (KD values ranging from 23.2 nM to 529 nM). Notably, engineered multimeric tandem nanobodies (Nb1-Nb2-Nb3) achieved higher affinity (KD = 4.39 nM) compared to single nanobodies, as validated by ITC. Characterization via dynamic light scattering (DLS) further revealed colloidal stability of SOD1-nanobody complexes. These results provide the first atomic-resolution insights into multi-nanobody targeting of SOD1 without steric interference, establishing a foundation for developing high-affinity tools to detect and manipulate SOD1 in ALS and related neurodegenerative diseases.},
}
RevDate: 2025-12-05
CmpDate: 2025-12-05
Methodological Issues in Taquet et al.'s analysis preclude any conclusions regarding AS01 adjuvant's specific role in dementia prevention.
NPJ vaccines, 10(1):255.
Taquet et al. evaluated the impact of AS01-adjuvanted vaccines on subsequent dementia diagnosis[1]. The authors conclude: "No difference was observed between the two AS01-adjuvanted vaccines, suggesting that the AS01 adjuvant itself plays a direct role in lowering dementia risk". Although the study offers promising evidence, the inference regarding the role of AS01 adjuvant in dementia prevention is not convincingly supported by the presented data or other published literature[2].
Additional Links: PMID-41350294
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@article {pmid41350294,
year = {2025},
author = {Williams, SE and Luisi, K and Liang, C and Cane, A and Begier, E},
title = {Methodological Issues in Taquet et al.'s analysis preclude any conclusions regarding AS01 adjuvant's specific role in dementia prevention.},
journal = {NPJ vaccines},
volume = {10},
number = {1},
pages = {255},
pmid = {41350294},
issn = {2059-0105},
abstract = {Taquet et al. evaluated the impact of AS01-adjuvanted vaccines on subsequent dementia diagnosis[1]. The authors conclude: "No difference was observed between the two AS01-adjuvanted vaccines, suggesting that the AS01 adjuvant itself plays a direct role in lowering dementia risk". Although the study offers promising evidence, the inference regarding the role of AS01 adjuvant in dementia prevention is not convincingly supported by the presented data or other published literature[2].},
}
RevDate: 2025-12-05
Reply to the letter by Marimbun et al. on fasciculation awareness in ALS.
Additional Links: PMID-41350201
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@article {pmid41350201,
year = {2025},
author = {Hokkoku, K and Inoue, M and Yamada, S and Namba, H and Matsukura, K and Mukai, T and Chiba, T and Hatanaka, Y and Kobayashi, S and Sonoo, M},
title = {Reply to the letter by Marimbun et al. on fasciculation awareness in ALS.},
journal = {Journal of the neurological sciences},
volume = {},
number = {},
pages = {125677},
doi = {10.1016/j.jns.2025.125677},
pmid = {41350201},
issn = {1878-5883},
}
RevDate: 2025-12-05
CmpDate: 2025-12-05
Integrating network toxicology and molecular docking to uncover mechanisms of novel herbicide-induced neurodegeneration.
Pesticide biochemistry and physiology, 216(Pt 2):106821.
Rising global reliance on novel herbicides has outpaced understanding of their potential neurotoxicity. This study employs an integrative network-toxicology pipeline to clarify how five widely used compounds, including mesotrione, topramezone, flufenazopyr, glufosinate-ammonium and beflubutamid-M, may contribute to Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis pathogenesis. We first predicted toxic liabilities in eMolTox, SwissADME and ProTox, then harvested 310 human targets via PubChem, ChEMBL, STITCH and Swiss Target Prediction. Intersection with 3668-3429 disease genes (GeneCards/ OMIM) revealed 91-176 shared targets per disorder. PPI networks constructed in STRING and refined with Cytoscape (MCODE, cytoHubba) and novel NodeIdentifyR algorithm converged on eleven high-impact hub genes: EGFR, GSK3B, SRC, AKT1, MAPT, CASP3, MMP9, MTOR, PTK2, BCL2L1 and MAPK8. GO and KEGG enrichment analyses highlighted apoptosis, PI3K-Akt and MAPK signaling dysregulation. Single-cell and bulk transcriptomic atlases confirmed aberrant expression of these hubs in patient brains; Molecular docking demonstrated low-nanomolar affinities of all herbicides for multiple hub proteins, with mesotrione and topramezone displaying the broadest binding spectra and SRC emerging as a common high-affinity site. Molecular dynamics simulations supported stable binding in a representative herbicide-protein complex. Additionally, in vivo and in vitro experiments using Glufosinate-ammonium exposure corroborated the computational findings, underscoring the robustness of our approach. Together, these results establish a systems-level framework linking environmental herbicide exposure to neurodegeneration and nominate tractable targets for surveillance and therapeutic intervention.
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@article {pmid41350075,
year = {2026},
author = {Wu, G and Chen, Y and Yao, Y and Huang, W and Wu, K},
title = {Integrating network toxicology and molecular docking to uncover mechanisms of novel herbicide-induced neurodegeneration.},
journal = {Pesticide biochemistry and physiology},
volume = {216},
number = {Pt 2},
pages = {106821},
doi = {10.1016/j.pestbp.2025.106821},
pmid = {41350075},
issn = {1095-9939},
mesh = {*Herbicides/toxicity/chemistry ; *Molecular Docking Simulation ; Humans ; *Neurodegenerative Diseases/chemically induced/metabolism ; Protein Interaction Maps ; },
abstract = {Rising global reliance on novel herbicides has outpaced understanding of their potential neurotoxicity. This study employs an integrative network-toxicology pipeline to clarify how five widely used compounds, including mesotrione, topramezone, flufenazopyr, glufosinate-ammonium and beflubutamid-M, may contribute to Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis pathogenesis. We first predicted toxic liabilities in eMolTox, SwissADME and ProTox, then harvested 310 human targets via PubChem, ChEMBL, STITCH and Swiss Target Prediction. Intersection with 3668-3429 disease genes (GeneCards/ OMIM) revealed 91-176 shared targets per disorder. PPI networks constructed in STRING and refined with Cytoscape (MCODE, cytoHubba) and novel NodeIdentifyR algorithm converged on eleven high-impact hub genes: EGFR, GSK3B, SRC, AKT1, MAPT, CASP3, MMP9, MTOR, PTK2, BCL2L1 and MAPK8. GO and KEGG enrichment analyses highlighted apoptosis, PI3K-Akt and MAPK signaling dysregulation. Single-cell and bulk transcriptomic atlases confirmed aberrant expression of these hubs in patient brains; Molecular docking demonstrated low-nanomolar affinities of all herbicides for multiple hub proteins, with mesotrione and topramezone displaying the broadest binding spectra and SRC emerging as a common high-affinity site. Molecular dynamics simulations supported stable binding in a representative herbicide-protein complex. Additionally, in vivo and in vitro experiments using Glufosinate-ammonium exposure corroborated the computational findings, underscoring the robustness of our approach. Together, these results establish a systems-level framework linking environmental herbicide exposure to neurodegeneration and nominate tractable targets for surveillance and therapeutic intervention.},
}
MeSH Terms:
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*Herbicides/toxicity/chemistry
*Molecular Docking Simulation
Humans
*Neurodegenerative Diseases/chemically induced/metabolism
Protein Interaction Maps
RevDate: 2025-12-05
CmpDate: 2025-12-05
ALS target-site mutations and overexpression synergistically enhance mesosulfuron resistance in Lolium perenne.
Pesticide biochemistry and physiology, 216(Pt 2):106802.
The invasive weed Lolium perenne (perennial ryegrass) poses a considerable threat to winter wheat crops in China and is hardly controlled by acetolactate synthase (ALS) inhibitors after years of application. In this study, four L. perenne populations from different locations in Henan were collected to evaluate the mechanisms of target site resistance to mesosulfuron-methyl. The resistant index (RI) of these four populations ranged from 122.73 to 149.26 compared to the susceptible population. ALS gene sequencing revealed three specific target site mutations: Pro-197-Thr, Asp-376-Glu, and Trp-574-Leu. Among these, Trp-574-Leu has not been previously reported in L. perenne. Three simultaneous double mutations were found in the same individual: Pro-197-Thr and Asp-376-Glu (Group I); Pro-197-Thr and Trp-574-Leu (Group II); and Asp-376-Glu and Trp-574-Leu (Group III). The gene expression levels of the double mutant groups were significantly higher than those of the susceptible plants. The I50 values obtained from the ALS enzyme assays showed that all three double mutant groups demonstrated a 136.75 to 149-fold increase compared to the enzyme activity of susceptible plants. Molecular docking analysis of mutant ALS proteins with mesosulfuron-methyl indicated that the mutant proteins had a reduced binding affinity to the herbicide. This reduced affinity was due to the disruption of hydrogen bonds and other key interactions, which contributed to increased herbicide resistance. Double target site mutations in a single ALS gene are a crucial mechanism for conferring high levels of mesosulfuron-methyl resistance in L. perenne.
Additional Links: PMID-41350059
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PubMed:
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@article {pmid41350059,
year = {2026},
author = {Sarker, SC and Chen, J and Wang, C and He, S and Yu, H and Li, X and Cui, H},
title = {ALS target-site mutations and overexpression synergistically enhance mesosulfuron resistance in Lolium perenne.},
journal = {Pesticide biochemistry and physiology},
volume = {216},
number = {Pt 2},
pages = {106802},
doi = {10.1016/j.pestbp.2025.106802},
pmid = {41350059},
issn = {1095-9939},
mesh = {*Acetolactate Synthase/genetics/metabolism ; *Lolium/genetics/drug effects/enzymology ; *Herbicide Resistance/genetics ; *Sulfonylurea Compounds/pharmacology ; Mutation ; *Herbicides/pharmacology ; *Plant Proteins/genetics/metabolism ; },
abstract = {The invasive weed Lolium perenne (perennial ryegrass) poses a considerable threat to winter wheat crops in China and is hardly controlled by acetolactate synthase (ALS) inhibitors after years of application. In this study, four L. perenne populations from different locations in Henan were collected to evaluate the mechanisms of target site resistance to mesosulfuron-methyl. The resistant index (RI) of these four populations ranged from 122.73 to 149.26 compared to the susceptible population. ALS gene sequencing revealed three specific target site mutations: Pro-197-Thr, Asp-376-Glu, and Trp-574-Leu. Among these, Trp-574-Leu has not been previously reported in L. perenne. Three simultaneous double mutations were found in the same individual: Pro-197-Thr and Asp-376-Glu (Group I); Pro-197-Thr and Trp-574-Leu (Group II); and Asp-376-Glu and Trp-574-Leu (Group III). The gene expression levels of the double mutant groups were significantly higher than those of the susceptible plants. The I50 values obtained from the ALS enzyme assays showed that all three double mutant groups demonstrated a 136.75 to 149-fold increase compared to the enzyme activity of susceptible plants. Molecular docking analysis of mutant ALS proteins with mesosulfuron-methyl indicated that the mutant proteins had a reduced binding affinity to the herbicide. This reduced affinity was due to the disruption of hydrogen bonds and other key interactions, which contributed to increased herbicide resistance. Double target site mutations in a single ALS gene are a crucial mechanism for conferring high levels of mesosulfuron-methyl resistance in L. perenne.},
}
MeSH Terms:
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*Acetolactate Synthase/genetics/metabolism
*Lolium/genetics/drug effects/enzymology
*Herbicide Resistance/genetics
*Sulfonylurea Compounds/pharmacology
Mutation
*Herbicides/pharmacology
*Plant Proteins/genetics/metabolism
RevDate: 2025-12-05
Divergence of cortical neurophysiology across different neurodegenerative disorders compared to healthy ageing.
Progress in neurobiology pii:S0301-0082(25)00156-X [Epub ahead of print].
Neurodegenerative diseases involve disruption of healthy brain network communication occurring before the emergence of symptoms. Magnetoencephalography (MEG) is sensitive to the magnetic fields generated by cortical neuronal activity, and the most spatio-temporally accurate method of directly assessing neuronal activity non-invasively. We used MEG to directly compare three neurodegenerative disorders against a large healthy cohort to characterise patterns of activity deviating from healthy ageing. Task-free MEG recordings were acquired from patients with Alzheimer's disease (AD, n=29), Parkinson's disease (PD, n=25), amyotrophic lateral sclerosis (ALS, n=33) and healthy controls (HC, n=191). Healthy ageing trajectories for metrics including spectral power (local neuronal recruitment), connectivity (long-range communication), 1/f exponent (which may reflect inhibition), and oscillatory speed were extracted. These metrics were compared pairwise between HC and patient groups, correcting for age and sex. The modelled trajectories of healthy ageing included increasing beta power and oscillatory speed, with reduced power spectrum slope. PD, AD, and ALS groups all showed reductions in beta power and slowing of oscillatory activity compared to matched HC. In AD, older patients showed lower beta power compared to younger patients. Compared to matched HC, the power spectrum slope was uniquely reduced in ALS, in contrast to the increase seen in PD and AD. Gamma connectivity increased in AD and ALS. MEG has unique potential as a source of biomarkers that might be used to detect deviation from healthy ageing if applied at an earlier presymptomatic stage of neurodegeneration than current tools permit. It might also provide outcome measures for prevention trials.
Additional Links: PMID-41349953
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PubMed:
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@article {pmid41349953,
year = {2025},
author = {Trubshaw, M and Kohl, O and Gohil, C and van Es, MWJ and Quinn, AJ and Yoganathan, K and Edmond, E and Proudfoot, M and Zokaei, N and Raymont, V and Pitt, J and Thayanandan, T and Thompson, AG and Talbot, K and Hu, MT and Perquin, MN and Kocagoncu, E and Rowe, JB and Woolrich, MW and Nobre, AC and Turner, MR},
title = {Divergence of cortical neurophysiology across different neurodegenerative disorders compared to healthy ageing.},
journal = {Progress in neurobiology},
volume = {},
number = {},
pages = {102865},
doi = {10.1016/j.pneurobio.2025.102865},
pmid = {41349953},
issn = {1873-5118},
abstract = {Neurodegenerative diseases involve disruption of healthy brain network communication occurring before the emergence of symptoms. Magnetoencephalography (MEG) is sensitive to the magnetic fields generated by cortical neuronal activity, and the most spatio-temporally accurate method of directly assessing neuronal activity non-invasively. We used MEG to directly compare three neurodegenerative disorders against a large healthy cohort to characterise patterns of activity deviating from healthy ageing. Task-free MEG recordings were acquired from patients with Alzheimer's disease (AD, n=29), Parkinson's disease (PD, n=25), amyotrophic lateral sclerosis (ALS, n=33) and healthy controls (HC, n=191). Healthy ageing trajectories for metrics including spectral power (local neuronal recruitment), connectivity (long-range communication), 1/f exponent (which may reflect inhibition), and oscillatory speed were extracted. These metrics were compared pairwise between HC and patient groups, correcting for age and sex. The modelled trajectories of healthy ageing included increasing beta power and oscillatory speed, with reduced power spectrum slope. PD, AD, and ALS groups all showed reductions in beta power and slowing of oscillatory activity compared to matched HC. In AD, older patients showed lower beta power compared to younger patients. Compared to matched HC, the power spectrum slope was uniquely reduced in ALS, in contrast to the increase seen in PD and AD. Gamma connectivity increased in AD and ALS. MEG has unique potential as a source of biomarkers that might be used to detect deviation from healthy ageing if applied at an earlier presymptomatic stage of neurodegeneration than current tools permit. It might also provide outcome measures for prevention trials.},
}
RevDate: 2025-12-05
Efficacy of Hybrid Sleeve-Assisted Surgery for Spinal Dural Arteriovenous Fistula.
World neurosurgery pii:S1878-8750(25)01060-5 [Epub ahead of print].
BACKGROUND: This study aimed to evaluate the efficacy of hybrid surgery combined with the sleeve technique in treating spinal dural arteriovenous fistula (SDAVF).
METHODS: A retrospective analysis was conducted on the clinical data of 16 patients with SDAVF who underwent hybrid surgery between October 2020 and June 2024. Spinal-cord function was quantitatively assessed pre- and post-operatively using the modified Aminoff-Logue Scale (ALS). Postoperative follow-up was 1-36 months. A decrease in the ALS score indicated functional improvement, whereas an increase indicated deterioration.
RESULTS: Intraoperative spinal digital subtraction angiography results confirmed the complete disappearance of the fistulas in all the 16 cases. Thirteen patients (81%) exhibited improved spinal-cord function, whereas three patients showed no changes.
CONCLUSIONS: Hybrid sleeve-assisted surgery integrates the advantages of endovascular interventional therapy and microsurgery, reducing late recurrence and surgical trauma. Consequently, this combined approach represents a valuable, clinically translatable therapeutic modality for the management of SDAVF.
Additional Links: PMID-41349919
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PubMed:
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@article {pmid41349919,
year = {2025},
author = {Liu, H and Liu, J and Wang, J and Gao, P and Liu, H and Li, B and Dai, X and Zhang, B},
title = {Efficacy of Hybrid Sleeve-Assisted Surgery for Spinal Dural Arteriovenous Fistula.},
journal = {World neurosurgery},
volume = {},
number = {},
pages = {124702},
doi = {10.1016/j.wneu.2025.124702},
pmid = {41349919},
issn = {1878-8769},
abstract = {BACKGROUND: This study aimed to evaluate the efficacy of hybrid surgery combined with the sleeve technique in treating spinal dural arteriovenous fistula (SDAVF).
METHODS: A retrospective analysis was conducted on the clinical data of 16 patients with SDAVF who underwent hybrid surgery between October 2020 and June 2024. Spinal-cord function was quantitatively assessed pre- and post-operatively using the modified Aminoff-Logue Scale (ALS). Postoperative follow-up was 1-36 months. A decrease in the ALS score indicated functional improvement, whereas an increase indicated deterioration.
RESULTS: Intraoperative spinal digital subtraction angiography results confirmed the complete disappearance of the fistulas in all the 16 cases. Thirteen patients (81%) exhibited improved spinal-cord function, whereas three patients showed no changes.
CONCLUSIONS: Hybrid sleeve-assisted surgery integrates the advantages of endovascular interventional therapy and microsurgery, reducing late recurrence and surgical trauma. Consequently, this combined approach represents a valuable, clinically translatable therapeutic modality for the management of SDAVF.},
}
RevDate: 2025-12-05
Hypoxic stress is an early pathogenic event in human VCP-mutant ALS astrocytes.
Stem cell reports pii:S2213-6711(25)00327-3 [Epub ahead of print].
Astrocytes are essential regulators of neuronal health, and their dysfunction contributes to neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Using human induced pluripotent stem cell (iPSC)-derived astrocytes carrying ALS-associated VCP mutations, we uncover cell-autonomous activation of the hypoxia response under basal conditions. VCP-mutant astrocytes exhibit increased nuclear hypoxia-inducible factor (HIF)-1ɑ, mitochondrial depolarization, and lipid droplet accumulation. Mimicking hypoxia in control astrocytes by HIF-1ɑ stabilization with dimethyloxalylglycine recapitulates these phenotypes. Transcriptomic and CUT&RUN profiling reveal direct HIF-1ɑ binding to canonical hypoxia-responsive genes in VCP-mutant astrocytes and a transcriptional signature of metabolic reprogramming and mitochondrial dysfunction under normoxia. Furthermore, conditioned medium from hypoxia-exposed astrocytes fails to rescue RNA-binding protein mislocalization in motor neurons, unlike medium from healthy counterparts. Together, these findings demonstrate that aberrant HIF-1ɑ activation drives astrocytic dysfunction and compromises neuronal support, identifying hypoxic stress as an early and functionally consequential event in VCP-mutant ALS, with therapeutic implications for targeting HIF-1ɑ signaling.
Additional Links: PMID-41349534
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PubMed:
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@article {pmid41349534,
year = {2025},
author = {Franklin, HD and Crerar, H and Parnandi, N and Lattke, M and Majewski, S and Clarke, BE and Pallikonda, H and Howell, M and Boulton, SJ and Patani, R},
title = {Hypoxic stress is an early pathogenic event in human VCP-mutant ALS astrocytes.},
journal = {Stem cell reports},
volume = {},
number = {},
pages = {102723},
doi = {10.1016/j.stemcr.2025.102723},
pmid = {41349534},
issn = {2213-6711},
abstract = {Astrocytes are essential regulators of neuronal health, and their dysfunction contributes to neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Using human induced pluripotent stem cell (iPSC)-derived astrocytes carrying ALS-associated VCP mutations, we uncover cell-autonomous activation of the hypoxia response under basal conditions. VCP-mutant astrocytes exhibit increased nuclear hypoxia-inducible factor (HIF)-1ɑ, mitochondrial depolarization, and lipid droplet accumulation. Mimicking hypoxia in control astrocytes by HIF-1ɑ stabilization with dimethyloxalylglycine recapitulates these phenotypes. Transcriptomic and CUT&RUN profiling reveal direct HIF-1ɑ binding to canonical hypoxia-responsive genes in VCP-mutant astrocytes and a transcriptional signature of metabolic reprogramming and mitochondrial dysfunction under normoxia. Furthermore, conditioned medium from hypoxia-exposed astrocytes fails to rescue RNA-binding protein mislocalization in motor neurons, unlike medium from healthy counterparts. Together, these findings demonstrate that aberrant HIF-1ɑ activation drives astrocytic dysfunction and compromises neuronal support, identifying hypoxic stress as an early and functionally consequential event in VCP-mutant ALS, with therapeutic implications for targeting HIF-1ɑ signaling.},
}
RevDate: 2025-12-05
Real-world evidence supporting orphan drugs approvals for rare neuromuscular disorders in the European Union and the United States: Review of public assessment reports (2015-2025).
Current opinion in pharmacology, 86:102586 pii:S1471-4892(25)00082-7 [Epub ahead of print].
Real-world data (RWD) and real-world evidence (RWE) are becoming essential complements to conventional clinical trials for drug assessment, particularly for rare neuromuscular disorders where small patient populations heighten outcome uncertainty. Robust RWE could reduce that uncertainty and inform regulatory decisions on orphan drugs (ODs). To review how the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) have incorporated RWE into OD approvals for neuromuscular diseases from January 2015 to January 2025. We reviewed all publicly available EMA European Public Assessment Reports and FDA review packages for ODs targeting neuromuscular indications. Each document was screened for mention of RWD sources and by the regulatory weight assigned to the resulting RWE. We identified 14 OD approvals by the EMA and 13 by the FDA, with greater use of RWE by the FDA. Indications comprised spinal muscular atrophy (3/3 EMA/FDA), amyotrophic lateral sclerosis (1/3), amyloid neuropathies (2/2), Friedreich ataxia (1/1), Lambert-Eaton syndrome (1/1), myasthenia gravis (2/2), myotonic disorders (1/0), and Duchenne muscular dystrophy (2/1). Among 18 evaluable dossiers, clinical outcome assessments (COA) were reported as follows: patient-reported outcomes - 39.1%, clinician-reported outcomes - 34.7%, observer-reported outcomes - 13.1 %, and performance outcomes - 13.1%. Only tofersen incorporated all COA types. The use of RWE for the evaluation of ODs is increasing for both the FDA and the EMA, more so for the former than for the latter. Harmonized methodological standards and transparent reporting frameworks are urgently needed to generate quality evidence that benefits stakeholders.
Additional Links: PMID-41349278
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@article {pmid41349278,
year = {2025},
author = {García-Parra, B and Guiu, JM and Povedano, M and Modamio, P},
title = {Real-world evidence supporting orphan drugs approvals for rare neuromuscular disorders in the European Union and the United States: Review of public assessment reports (2015-2025).},
journal = {Current opinion in pharmacology},
volume = {86},
number = {},
pages = {102586},
doi = {10.1016/j.coph.2025.102586},
pmid = {41349278},
issn = {1471-4973},
abstract = {Real-world data (RWD) and real-world evidence (RWE) are becoming essential complements to conventional clinical trials for drug assessment, particularly for rare neuromuscular disorders where small patient populations heighten outcome uncertainty. Robust RWE could reduce that uncertainty and inform regulatory decisions on orphan drugs (ODs). To review how the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) have incorporated RWE into OD approvals for neuromuscular diseases from January 2015 to January 2025. We reviewed all publicly available EMA European Public Assessment Reports and FDA review packages for ODs targeting neuromuscular indications. Each document was screened for mention of RWD sources and by the regulatory weight assigned to the resulting RWE. We identified 14 OD approvals by the EMA and 13 by the FDA, with greater use of RWE by the FDA. Indications comprised spinal muscular atrophy (3/3 EMA/FDA), amyotrophic lateral sclerosis (1/3), amyloid neuropathies (2/2), Friedreich ataxia (1/1), Lambert-Eaton syndrome (1/1), myasthenia gravis (2/2), myotonic disorders (1/0), and Duchenne muscular dystrophy (2/1). Among 18 evaluable dossiers, clinical outcome assessments (COA) were reported as follows: patient-reported outcomes - 39.1%, clinician-reported outcomes - 34.7%, observer-reported outcomes - 13.1 %, and performance outcomes - 13.1%. Only tofersen incorporated all COA types. The use of RWE for the evaluation of ODs is increasing for both the FDA and the EMA, more so for the former than for the latter. Harmonized methodological standards and transparent reporting frameworks are urgently needed to generate quality evidence that benefits stakeholders.},
}
RevDate: 2025-12-05
CmpDate: 2025-12-05
Early assessment in bulbar-onset amyotrophic lateral sclerosis detects similar rates of nocturnal desaturation and orthopnoea compared to non-bulbar-onset disease.
Sleep & breathing = Schlaf & Atmung, 30(1):3.
BACKGROUND: Pulmonary function measures are commonly used to determine timing of non-invasive ventilation (NIV) initiation in amyotrophic lateral sclerosis (ALS). However, these tests may be difficult to perform and unreliable in those with bulbar disease. We evaluated the rates of orthopnoea and nocturnal desaturation detected using nocturnal pulse oximetry (NPO), two key criteria for NIV initiation, separately in people with bulbar-onset and non-bulbar-onset ALS.
METHODS: We conducted a retrospective analysis of 93 individuals with ALS undergoing three consecutive nights of NPO screening. Demographics, diurnal respiratory function measures and NPO data were compared. Nocturnal desaturation was defined as > 2% of total sleep time with oxygen saturation < 90%.
RESULTS: Twenty-nine people had bulbar-onset ALS and 64 had non-bulbar-onset ALS. The prevalence of orthopnoea and the proportion with nocturnal desaturation were similar between bulbar-onset and non-bulbar-onset groups (24% vs. 20% and 76% vs. 67%, respectively). People with bulbar-onset ALS were older and underwent initial oximetry earlier in their disease trajectory following ALS-symptom onset than those with non-bulbar-onset ALS (67 ± 10.5 vs. 61 ± 11.9 years old, p = 0.02 and 17.5 (11.00-24.75) vs. 31.0 (18.00-63.50) months, p = 0.005, respectively).
CONCLUSION: People with bulbar-onset ALS were assessed with NPO sooner, but nocturnal desaturation was detected at similar rates to those with non-bulbar-onset ALS. Absence of orthopnoea and preserved lung function were poor indicators of nocturnal desaturation in both groups. Given the difficulties performing respiratory function tests in people with bulbar disease, early and regular NPO assessment in bulbar-onset ALS is warranted, even without symptoms.
Additional Links: PMID-41348294
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@article {pmid41348294,
year = {2025},
author = {Luu, S and McGuiness, OA and Menadue, C and Piper, AJ and Wong, KK and Yee, BJ and Gray, EL},
title = {Early assessment in bulbar-onset amyotrophic lateral sclerosis detects similar rates of nocturnal desaturation and orthopnoea compared to non-bulbar-onset disease.},
journal = {Sleep & breathing = Schlaf & Atmung},
volume = {30},
number = {1},
pages = {3},
pmid = {41348294},
issn = {1522-1709},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/epidemiology/classification/therapy/physiopathology ; Male ; Female ; Middle Aged ; *Oximetry ; Aged ; Retrospective Studies ; Early Diagnosis ; *Oxygen Saturation/physiology ; Polysomnography ; Noninvasive Ventilation ; },
abstract = {BACKGROUND: Pulmonary function measures are commonly used to determine timing of non-invasive ventilation (NIV) initiation in amyotrophic lateral sclerosis (ALS). However, these tests may be difficult to perform and unreliable in those with bulbar disease. We evaluated the rates of orthopnoea and nocturnal desaturation detected using nocturnal pulse oximetry (NPO), two key criteria for NIV initiation, separately in people with bulbar-onset and non-bulbar-onset ALS.
METHODS: We conducted a retrospective analysis of 93 individuals with ALS undergoing three consecutive nights of NPO screening. Demographics, diurnal respiratory function measures and NPO data were compared. Nocturnal desaturation was defined as > 2% of total sleep time with oxygen saturation < 90%.
RESULTS: Twenty-nine people had bulbar-onset ALS and 64 had non-bulbar-onset ALS. The prevalence of orthopnoea and the proportion with nocturnal desaturation were similar between bulbar-onset and non-bulbar-onset groups (24% vs. 20% and 76% vs. 67%, respectively). People with bulbar-onset ALS were older and underwent initial oximetry earlier in their disease trajectory following ALS-symptom onset than those with non-bulbar-onset ALS (67 ± 10.5 vs. 61 ± 11.9 years old, p = 0.02 and 17.5 (11.00-24.75) vs. 31.0 (18.00-63.50) months, p = 0.005, respectively).
CONCLUSION: People with bulbar-onset ALS were assessed with NPO sooner, but nocturnal desaturation was detected at similar rates to those with non-bulbar-onset ALS. Absence of orthopnoea and preserved lung function were poor indicators of nocturnal desaturation in both groups. Given the difficulties performing respiratory function tests in people with bulbar disease, early and regular NPO assessment in bulbar-onset ALS is warranted, even without symptoms.},
}
MeSH Terms:
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Humans
*Amyotrophic Lateral Sclerosis/diagnosis/epidemiology/classification/therapy/physiopathology
Male
Female
Middle Aged
*Oximetry
Aged
Retrospective Studies
Early Diagnosis
*Oxygen Saturation/physiology
Polysomnography
Noninvasive Ventilation
RevDate: 2025-12-05
CmpDate: 2025-12-05
Comment on "Baseline hemoglobin and neutrophil-to-lymphocyte ratio as prognostic biomarkers in patients with metastatic triple-negative breast cancer treated with sacituzumab govitecan in second line and beyond: a real-world analysis".
Breast cancer research and treatment, 215(1):29.
This commentary appraises Pieniążek et al.'s study on hematologic prognostic markers in sacituzumab govitecan-treated mTNBC, emphasizing residual confounding, absent Trop-2 data, limited modeling flexibility, and incomplete handling of missingness. Methodological refinement and integration of biological, longitudinal, and clinical variables are proposed to enhance prognostic accuracy and translational applicability.
Additional Links: PMID-41348236
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@article {pmid41348236,
year = {2025},
author = {Dedeepya, SD and Goel, V and Desai, NN},
title = {Comment on "Baseline hemoglobin and neutrophil-to-lymphocyte ratio as prognostic biomarkers in patients with metastatic triple-negative breast cancer treated with sacituzumab govitecan in second line and beyond: a real-world analysis".},
journal = {Breast cancer research and treatment},
volume = {215},
number = {1},
pages = {29},
pmid = {41348236},
issn = {1573-7217},
mesh = {Humans ; *Antibodies, Monoclonal, Humanized/therapeutic use ; Female ; *Triple Negative Breast Neoplasms/drug therapy/blood/pathology/mortality ; Prognosis ; *Neutrophils ; *Biomarkers, Tumor ; *Camptothecin/analogs & derivatives/therapeutic use ; *Hemoglobins/analysis/metabolism ; *Lymphocytes/pathology ; Immunoconjugates ; },
abstract = {This commentary appraises Pieniążek et al.'s study on hematologic prognostic markers in sacituzumab govitecan-treated mTNBC, emphasizing residual confounding, absent Trop-2 data, limited modeling flexibility, and incomplete handling of missingness. Methodological refinement and integration of biological, longitudinal, and clinical variables are proposed to enhance prognostic accuracy and translational applicability.},
}
MeSH Terms:
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Humans
*Antibodies, Monoclonal, Humanized/therapeutic use
Female
*Triple Negative Breast Neoplasms/drug therapy/blood/pathology/mortality
Prognosis
*Neutrophils
*Biomarkers, Tumor
*Camptothecin/analogs & derivatives/therapeutic use
*Hemoglobins/analysis/metabolism
*Lymphocytes/pathology
Immunoconjugates
RevDate: 2025-12-05
Integrating administrative health data and machine learning to predict ALS onset.
Amyotrophic lateral sclerosis & frontotemporal degeneration [Epub ahead of print].
BACKGROUND: This study aims to develop a Machine Learning (ML) model to predict the initial diagnosis of Amyotrophic Lateral Sclerosis (ALS).
METHODS: To predict ALS, a stacked model combining four ML algorithms-logistic Regression, Decision Tree, Random Forest, and Extreme Gradient Boosting-was implemented. The analysis utilized healthcare administrative data from Catalonia, encompassing 2,924,590 elderly individuals from 2014 to 2021, which were linked to socioeconomic factors and medication records.
RESULTS: The stacked model successfully predicted first-time ALS diagnoses, achieving an AUC of 0.86, with an accuracy of 0.86, specificity of 0.88, and sensitivity of 0.84. The most influential predictors included immunization encounters, South American origin, general medical and special examinations, hypertensive heart disease, and counseling. Other relevant features were sciatica, heart failure, liver metastases, healthcare use patterns, and chronic conditions such as hypertension, kidney disease, and hypercholesterolemia. These features reflect early clinical symptoms and healthcare usage patterns relevant to ALS detection.
CONCLUSIONS: Machine Learning models, particularly stacked approaches, show promising results in predicting ALS diagnoses using administrative health data. Continued research is necessary to improve detection strategies and support their integration into healthcare systems.
Additional Links: PMID-41347776
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@article {pmid41347776,
year = {2025},
author = {Mora, T and Roche, D and Andrés Benito, P and Caravaca Puchades, A and Povedano, M},
title = {Integrating administrative health data and machine learning to predict ALS onset.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-7},
doi = {10.1080/21678421.2025.2596691},
pmid = {41347776},
issn = {2167-9223},
abstract = {BACKGROUND: This study aims to develop a Machine Learning (ML) model to predict the initial diagnosis of Amyotrophic Lateral Sclerosis (ALS).
METHODS: To predict ALS, a stacked model combining four ML algorithms-logistic Regression, Decision Tree, Random Forest, and Extreme Gradient Boosting-was implemented. The analysis utilized healthcare administrative data from Catalonia, encompassing 2,924,590 elderly individuals from 2014 to 2021, which were linked to socioeconomic factors and medication records.
RESULTS: The stacked model successfully predicted first-time ALS diagnoses, achieving an AUC of 0.86, with an accuracy of 0.86, specificity of 0.88, and sensitivity of 0.84. The most influential predictors included immunization encounters, South American origin, general medical and special examinations, hypertensive heart disease, and counseling. Other relevant features were sciatica, heart failure, liver metastases, healthcare use patterns, and chronic conditions such as hypertension, kidney disease, and hypercholesterolemia. These features reflect early clinical symptoms and healthcare usage patterns relevant to ALS detection.
CONCLUSIONS: Machine Learning models, particularly stacked approaches, show promising results in predicting ALS diagnoses using administrative health data. Continued research is necessary to improve detection strategies and support their integration into healthcare systems.},
}
RevDate: 2025-12-05
Effects of a Coach-Guided Online Yogic Breathing Program on Quality of Life in People With Amyotrophic Lateral Sclerosis: A Mixed-Methods Pilot RCT.
The American journal of hospice & palliative care [Epub ahead of print].
ObjectivesThis study aims to evaluate the feasibility and acceptability of an online coach-guided yogic breathing exercise (YBE) program on improving quality of life (QoL) in persons with amyotrophic lateral sclerosis (PwALS).MethodsA waitlist pilot randomized controlled trial with a post-program individual qualitative interview was employed. Thirteen adults with ALS participated in the YBE program, with 7 in the YBE group and 6 in the waitlist group. The program consisted of twelve 30-min online YBE sessions in which each participant received one-on-one coaching from a certified yoga therapist over six consecutive weeks. ALS Specific Quality of Life-Revised (ALSSQOL-R) was the outcome measure.ResultsAll but 2 participants in the YBE training group completed the 12 sessions, with an overall attendance rate of >97%. Compared to the waitlist group using the Mann-Whitney U test, the YBE group showed significant improvement in the change scores of the physical symptoms and intimacy domains of the ALSQOL-R at post-test. No significant differences in the change scores between the YBE and waitlist groups in the total score and other domains of the ALSQOL-R were observed. Thematic analysis of participants' interview about their experiences with the program revealed two themes: sense of control over breathing and emotional regulation through relaxation.ConclusionDespite the small sample size, the high attendance rate and positive feedback indicate that the YBE program is feasible and acceptable to PwALS. The YBE program demonstrated significant QoL benefits for PwALS. Participants reported enhanced control over their breathing and better emotional regulation.
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@article {pmid41347668,
year = {2025},
author = {Yuen, HK and Szynkiewicz, SH and Richardson, K and Benge, M and Lowman, JD and Spraberry, SB and Jiang, N and Kazamel, M},
title = {Effects of a Coach-Guided Online Yogic Breathing Program on Quality of Life in People With Amyotrophic Lateral Sclerosis: A Mixed-Methods Pilot RCT.},
journal = {The American journal of hospice & palliative care},
volume = {},
number = {},
pages = {10499091251403506},
doi = {10.1177/10499091251403506},
pmid = {41347668},
issn = {1938-2715},
abstract = {ObjectivesThis study aims to evaluate the feasibility and acceptability of an online coach-guided yogic breathing exercise (YBE) program on improving quality of life (QoL) in persons with amyotrophic lateral sclerosis (PwALS).MethodsA waitlist pilot randomized controlled trial with a post-program individual qualitative interview was employed. Thirteen adults with ALS participated in the YBE program, with 7 in the YBE group and 6 in the waitlist group. The program consisted of twelve 30-min online YBE sessions in which each participant received one-on-one coaching from a certified yoga therapist over six consecutive weeks. ALS Specific Quality of Life-Revised (ALSSQOL-R) was the outcome measure.ResultsAll but 2 participants in the YBE training group completed the 12 sessions, with an overall attendance rate of >97%. Compared to the waitlist group using the Mann-Whitney U test, the YBE group showed significant improvement in the change scores of the physical symptoms and intimacy domains of the ALSQOL-R at post-test. No significant differences in the change scores between the YBE and waitlist groups in the total score and other domains of the ALSQOL-R were observed. Thematic analysis of participants' interview about their experiences with the program revealed two themes: sense of control over breathing and emotional regulation through relaxation.ConclusionDespite the small sample size, the high attendance rate and positive feedback indicate that the YBE program is feasible and acceptable to PwALS. The YBE program demonstrated significant QoL benefits for PwALS. Participants reported enhanced control over their breathing and better emotional regulation.},
}
RevDate: 2025-12-05
CmpDate: 2025-12-05
Comment on a Multicenter Retrospective Descriptive and Analytical Study of 129 Cases of Trichoteiromania.
International journal of trichology, 17(3):265-267.
We have read Ramos Costa et al.'s publication "Trichoteiromania: A multicentre retrospective descriptive and analytical study of 129 cases" in the Journal of the European Academy of Dermatology, and comment on some critical issues related to the nosology, nomenclature, and methodology. The term trichoteiromania was originally coined for the rubbing of the hair due to an underlying psychiatric disorder without further specifications. Based on case observations of patients with trichoteiromania, it was later reported that in contrast to trichotillomania that represents an obsessive-compulsive disorder, the underlying disorder in trichoteiromania varies among patients. Histopathological features are unspecific, while the traumatic changes to the hair shaft are more conspicuous, and 15 min of rubbing the hair is sufficient for hair breakage. Therefore, a clear distinction must be made between trichotillomania, trichoteiromania, neurotic excoriations, factitious dermatitis, lichen simplex chronicus, and nodular prurigo of the scalp, while the dermoscopic findings provided by Ramos Costa et al. showed the mechanics of hair damage without a deeper insight into its etiology. Trichoscopy has gained disproportionate popularity for the differential diagnosis of the hair and scalp disorders since its introduction into dermatologic practice, and as a self-reliant examination technique, it can even be misleading. As a diagnostic procedure, trichoscopy is to be understood as representing an integral part of a more comprehensive dermatological learning, to include a stringent nosological classification and nomenclature of diseases, based on a pathogenic understanding. Specifically, in trichoteiromania studies with a more detailed assessment of the psychopathological status will be of more value to determine disease management strategies, specifically approaches to psychotherapeutic, behavioral, and pharmacological interventions aimed at reducing or eliminating the hair-rubbing behavior. Regrettably, the majority of recent publications on trichoteiromania have been based on trichoscopy without any disease-relevant insights, and obviously, the editors and reviewers of the respective publishing journals have so far failed to acknowledge this major shortcoming.
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@article {pmid41346550,
year = {2025},
author = {Trüeb, RM and Romanova, Y and Gadzhigoroeva, A and Vavilov, V and Uribe, NC and Bielsa, CG},
title = {Comment on a Multicenter Retrospective Descriptive and Analytical Study of 129 Cases of Trichoteiromania.},
journal = {International journal of trichology},
volume = {17},
number = {3},
pages = {265-267},
pmid = {41346550},
issn = {0974-7753},
abstract = {We have read Ramos Costa et al.'s publication "Trichoteiromania: A multicentre retrospective descriptive and analytical study of 129 cases" in the Journal of the European Academy of Dermatology, and comment on some critical issues related to the nosology, nomenclature, and methodology. The term trichoteiromania was originally coined for the rubbing of the hair due to an underlying psychiatric disorder without further specifications. Based on case observations of patients with trichoteiromania, it was later reported that in contrast to trichotillomania that represents an obsessive-compulsive disorder, the underlying disorder in trichoteiromania varies among patients. Histopathological features are unspecific, while the traumatic changes to the hair shaft are more conspicuous, and 15 min of rubbing the hair is sufficient for hair breakage. Therefore, a clear distinction must be made between trichotillomania, trichoteiromania, neurotic excoriations, factitious dermatitis, lichen simplex chronicus, and nodular prurigo of the scalp, while the dermoscopic findings provided by Ramos Costa et al. showed the mechanics of hair damage without a deeper insight into its etiology. Trichoscopy has gained disproportionate popularity for the differential diagnosis of the hair and scalp disorders since its introduction into dermatologic practice, and as a self-reliant examination technique, it can even be misleading. As a diagnostic procedure, trichoscopy is to be understood as representing an integral part of a more comprehensive dermatological learning, to include a stringent nosological classification and nomenclature of diseases, based on a pathogenic understanding. Specifically, in trichoteiromania studies with a more detailed assessment of the psychopathological status will be of more value to determine disease management strategies, specifically approaches to psychotherapeutic, behavioral, and pharmacological interventions aimed at reducing or eliminating the hair-rubbing behavior. Regrettably, the majority of recent publications on trichoteiromania have been based on trichoscopy without any disease-relevant insights, and obviously, the editors and reviewers of the respective publishing journals have so far failed to acknowledge this major shortcoming.},
}
RevDate: 2025-12-04
Restless legs syndrome as a comorbidity in amyotrophic lateral sclerosis: a systematic review and meta-analysis.
BMC neurology pii:10.1186/s12883-025-04543-4 [Epub ahead of print].
BACKGROUND: Restless Legs Syndrome (RLS), characterized by an urge to move the legs, is linked to neurodegenerative diseases. Emerging evidence suggests a higher RLS prevalence in Amyotrophic Lateral Sclerosis (ALS), impacting quality of life. However, there is lack of comprehensive review addressing its prevalence and associated risk factors. This meta-analysis estimates RLS prevalence in ALS patients compared to healthy controls.
METHODS: We searched PubMed, Embase, Web of Science, and Scopus for studies assessing RLS in ALS patients versus controls, adhering to PRISMA guidelines. Two reviewers independently extracted data and assessed bias using Joanna Briggs Institute (JBI) checklist. Meta-analysis used Comprehensive Meta-Analysis software with a random-effects model due to heterogeneity. The certainty of evidence was appraised using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework.
RESULTS: Out of 291 studies, eight studies (792 ALS, 716 controls) were included. The pooled RLS prevalence in ALS was 17% (95% CI: 14.0%-21.1%; I²: 56.5%; p-value < 0.001). The fixed effect meta-analysis of four studies indicated that the difference of RLS prevalence was statically significant between patients with ALS and healthy controls (OR: 5.65; CI: 2.86-11.13; P-value < 0.001; I²: 28.7.).
CONCLUSION: RLS is significantly more prevalent in ALS patients, potentially worsening sleep and quality of life, mental health, and social well-being. Therefore, it is essential to draw clinicians' attention to RLS in ALS patients due to its potential impact on overall health.
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@article {pmid41345582,
year = {2025},
author = {Ebrahimian, A and Moradi, A and Athari, SZ and Farajdokht, F},
title = {Restless legs syndrome as a comorbidity in amyotrophic lateral sclerosis: a systematic review and meta-analysis.},
journal = {BMC neurology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12883-025-04543-4},
pmid = {41345582},
issn = {1471-2377},
support = {74962//Student Research Committee, Tabriz University of Medical Sciences/ ; },
abstract = {BACKGROUND: Restless Legs Syndrome (RLS), characterized by an urge to move the legs, is linked to neurodegenerative diseases. Emerging evidence suggests a higher RLS prevalence in Amyotrophic Lateral Sclerosis (ALS), impacting quality of life. However, there is lack of comprehensive review addressing its prevalence and associated risk factors. This meta-analysis estimates RLS prevalence in ALS patients compared to healthy controls.
METHODS: We searched PubMed, Embase, Web of Science, and Scopus for studies assessing RLS in ALS patients versus controls, adhering to PRISMA guidelines. Two reviewers independently extracted data and assessed bias using Joanna Briggs Institute (JBI) checklist. Meta-analysis used Comprehensive Meta-Analysis software with a random-effects model due to heterogeneity. The certainty of evidence was appraised using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework.
RESULTS: Out of 291 studies, eight studies (792 ALS, 716 controls) were included. The pooled RLS prevalence in ALS was 17% (95% CI: 14.0%-21.1%; I²: 56.5%; p-value < 0.001). The fixed effect meta-analysis of four studies indicated that the difference of RLS prevalence was statically significant between patients with ALS and healthy controls (OR: 5.65; CI: 2.86-11.13; P-value < 0.001; I²: 28.7.).
CONCLUSION: RLS is significantly more prevalent in ALS patients, potentially worsening sleep and quality of life, mental health, and social well-being. Therefore, it is essential to draw clinicians' attention to RLS in ALS patients due to its potential impact on overall health.},
}
RevDate: 2025-12-04
Correlation analysis of serum neurofilament light chain and glial fibrillary acidic protein levels with amyotrophic lateral sclerosis.
Scientific reports pii:10.1038/s41598-025-30022-4 [Epub ahead of print].
Neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP) are considered to be a promising biomarker for the diagnosis of amyotrophic lateral sclerosis (ALS) and assessment of disease progression. To investigate the correlation between serum neurofilament light chain protein (NFL) and glial fibrillary acidic protein (GFAP) levels and amyotrophic lateral sclerosis (ALS). Serum NFL and GFAP levels were measured in 12 ALS patients and 12 healthy controls (HC) using the Single-molecule array (Simoa) technique. Serum NFL and GFAP levels in ALS patients were 81.49 ± 47.06 pg/mL and 104.42 ± 37.31 pg/mL, respectively, significantly higher than those in healthy controls (9.21 ± 3.05 pg/mL and 57.71 ± 11.64 pg/mL; P < 0.001). Serum NFL and GFAP levels in ALS patients were correlated with the duration of the disease as respectively (r = 0.746, P = 0.005; r = 0.668, P = 0.018). In this study, we investigated the diagnostic value of serum NFL and GFAP levels in the ALS population and their clinical significance using the Simoa technique. The results showed that serum NFL and GFAP levels may be potential biomarkers for ALS diagnosis, and is positively correlated with disease progression. However, its diagnostic specificity awaits further studies that include disease controls.
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@article {pmid41345490,
year = {2025},
author = {Ji, C and Li, P and Ma, S and Li, J and Zhou, J and Zhu, J and Dong, D and Yang, T and Yang, P},
title = {Correlation analysis of serum neurofilament light chain and glial fibrillary acidic protein levels with amyotrophic lateral sclerosis.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-025-30022-4},
pmid = {41345490},
issn = {2045-2322},
support = {2021BEG03032//Key Research and Development Program of Ningxia/ ; },
abstract = {Neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP) are considered to be a promising biomarker for the diagnosis of amyotrophic lateral sclerosis (ALS) and assessment of disease progression. To investigate the correlation between serum neurofilament light chain protein (NFL) and glial fibrillary acidic protein (GFAP) levels and amyotrophic lateral sclerosis (ALS). Serum NFL and GFAP levels were measured in 12 ALS patients and 12 healthy controls (HC) using the Single-molecule array (Simoa) technique. Serum NFL and GFAP levels in ALS patients were 81.49 ± 47.06 pg/mL and 104.42 ± 37.31 pg/mL, respectively, significantly higher than those in healthy controls (9.21 ± 3.05 pg/mL and 57.71 ± 11.64 pg/mL; P < 0.001). Serum NFL and GFAP levels in ALS patients were correlated with the duration of the disease as respectively (r = 0.746, P = 0.005; r = 0.668, P = 0.018). In this study, we investigated the diagnostic value of serum NFL and GFAP levels in the ALS population and their clinical significance using the Simoa technique. The results showed that serum NFL and GFAP levels may be potential biomarkers for ALS diagnosis, and is positively correlated with disease progression. However, its diagnostic specificity awaits further studies that include disease controls.},
}
RevDate: 2025-12-04
CmpDate: 2025-12-04
Does the attentional window shed light on the attentional capture debate?.
Attention, perception & psychophysics, 88(1):31.
Belopolsky et al. (2007) provided evidence that capture occurs only when objects fall within the attentional window. This attentional window hypothesis was subsequently used to explain how salient stimuli can be powerful yet often have little or no observable effect. In the present study, we attempted to replicate their findings. Participants made a go/no-go decision based on the shape of the overall search array (diffuse attention) or based on the central fixation point (focused attention). Whereas Belopolsky et al. found larger capture effects from a color singleton distractor in the diffuse condition than the focused condition (where the color singleton is assumed to fall outside the attentional window), we found no such effect (Experiment 1). When we changed the task from a feature search task in Experiment 1 to a singleton search task in Experiment 2, capture effects increased overall but were once again similar for the diffuse and focused conditions. This pattern persisted even when we closely replicated Belopolsky et al.'s original design (Experiment 3). Our findings call into question the attentional window account and support an alternative account of why capture sometimes occurs: singleton search mode makes color singletons capture attention because participants are looking for singletons.
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@article {pmid41345292,
year = {2025},
author = {Ruthruff, E and Tolomeo, DA and Jain, S and Reitan, KM and Lien, MC},
title = {Does the attentional window shed light on the attentional capture debate?.},
journal = {Attention, perception & psychophysics},
volume = {88},
number = {1},
pages = {31},
pmid = {41345292},
issn = {1943-393X},
mesh = {Humans ; *Attention ; *Color Perception ; *Pattern Recognition, Visual ; Female ; Male ; Young Adult ; Adult ; Reaction Time ; },
abstract = {Belopolsky et al. (2007) provided evidence that capture occurs only when objects fall within the attentional window. This attentional window hypothesis was subsequently used to explain how salient stimuli can be powerful yet often have little or no observable effect. In the present study, we attempted to replicate their findings. Participants made a go/no-go decision based on the shape of the overall search array (diffuse attention) or based on the central fixation point (focused attention). Whereas Belopolsky et al. found larger capture effects from a color singleton distractor in the diffuse condition than the focused condition (where the color singleton is assumed to fall outside the attentional window), we found no such effect (Experiment 1). When we changed the task from a feature search task in Experiment 1 to a singleton search task in Experiment 2, capture effects increased overall but were once again similar for the diffuse and focused conditions. This pattern persisted even when we closely replicated Belopolsky et al.'s original design (Experiment 3). Our findings call into question the attentional window account and support an alternative account of why capture sometimes occurs: singleton search mode makes color singletons capture attention because participants are looking for singletons.},
}
MeSH Terms:
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Humans
*Attention
*Color Perception
*Pattern Recognition, Visual
Female
Male
Young Adult
Adult
Reaction Time
RevDate: 2025-12-04
An efficient dimensionality reduction framework using metaheuristic optimization with deep learning models for amyotrophic lateral sclerosis disease progression prediction.
Scientific reports pii:10.1038/s41598-025-30913-6 [Epub ahead of print].
Amyotrophic lateral sclerosis (ALS) is a disastrous neuro-degenerative infection which affects motor neuron inhabitants of the spinal cord, brainstem, and cerebral cortex, resulting in progressive disorder and demise from respiratory difficulty. ALS is considerably assorted disorder comprising symptoms such as muscle weakness, difficulty in swallowing, speaking, breathing, and changes in mental and emotional health. Hence, this disease requires more beneficial medication and also, successful treatment is affected by heterogeneous disease development, resulting in issues with patient stratification. Recently, many researches have been published by using deep learning (DL) and machine learning (ML) methods and, more commonly, artificial intelligence (AI). This paper presents a Dimensionality Reduction Framework Using Metaheuristic Optimization with Deep Learning Models for the Amyotrophic Lateral Sclerosis Disease Progression Prediction (DRMODL-ALSDP) method. The aim is to provide an effectual model for the progression prediction of ALS disease using advanced techniques. Initially, the data pre-processing stage applies min-mx normalization to transform raw data into a suitable format. Furthermore, SMOTE is employed to address class imbalance by upsampling the minority classes in disease progression stages. Furthermore, the binary swordfish movement optimization algorithm (BSMOA) technique is used for feature selection. Moreover, the hybrid of a temporal convolutional network and long short-term memory with attention mechanism (TCN-LSTM-AM) technique is employed for the classification process. Finally, the marine predator's algorithm (MPA) technique optimally fine-tunes the hyperparameter values and improves classification performance. A widespread simulation is performed to verify the performance of the DRMODL-ALSDP model. The comparison study of the DRMODL-ALSDP model accentuated the superior accuracy output of 98.17% over existing methods.
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@article {pmid41345272,
year = {2025},
author = {Duhayyim, MA},
title = {An efficient dimensionality reduction framework using metaheuristic optimization with deep learning models for amyotrophic lateral sclerosis disease progression prediction.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-025-30913-6},
pmid = {41345272},
issn = {2045-2322},
abstract = {Amyotrophic lateral sclerosis (ALS) is a disastrous neuro-degenerative infection which affects motor neuron inhabitants of the spinal cord, brainstem, and cerebral cortex, resulting in progressive disorder and demise from respiratory difficulty. ALS is considerably assorted disorder comprising symptoms such as muscle weakness, difficulty in swallowing, speaking, breathing, and changes in mental and emotional health. Hence, this disease requires more beneficial medication and also, successful treatment is affected by heterogeneous disease development, resulting in issues with patient stratification. Recently, many researches have been published by using deep learning (DL) and machine learning (ML) methods and, more commonly, artificial intelligence (AI). This paper presents a Dimensionality Reduction Framework Using Metaheuristic Optimization with Deep Learning Models for the Amyotrophic Lateral Sclerosis Disease Progression Prediction (DRMODL-ALSDP) method. The aim is to provide an effectual model for the progression prediction of ALS disease using advanced techniques. Initially, the data pre-processing stage applies min-mx normalization to transform raw data into a suitable format. Furthermore, SMOTE is employed to address class imbalance by upsampling the minority classes in disease progression stages. Furthermore, the binary swordfish movement optimization algorithm (BSMOA) technique is used for feature selection. Moreover, the hybrid of a temporal convolutional network and long short-term memory with attention mechanism (TCN-LSTM-AM) technique is employed for the classification process. Finally, the marine predator's algorithm (MPA) technique optimally fine-tunes the hyperparameter values and improves classification performance. A widespread simulation is performed to verify the performance of the DRMODL-ALSDP model. The comparison study of the DRMODL-ALSDP model accentuated the superior accuracy output of 98.17% over existing methods.},
}
RevDate: 2025-12-04
CmpDate: 2025-12-04
The Vap33 signaling axis precisely coordinates the timing of motoneuron dendritogenesis in neural map development.
Nature communications, 16(1):10893.
In Drosophila motoneurons, spatiotemporal dendritic patterns are established in the ventral nerve cord. While many guidance cues have been identified, the mechanisms of temporal regulation remain unknown. Previously, we identified the actin modulator Cdc42 GTPase as a key factor in this process. In this report, we further identify the upstream factors that activate Cdc42. Using single-cell genetics, FRET-based imaging, and biochemical techniques, we demonstrate that the guanine nucleotide exchange factor Vav is anchored to the plasma membrane via the Eph receptor tyrosine kinase, enabling Cdc42 activation. VAMP-associated protein 33 (Vap33), a potential Eph ligand supplied non-cell-autonomously, may induce Eph autophosphorylation, initiating downstream signaling. Traditionally known as an ER-resident protein, Vap33 is secreted extracellularly at the onset of Cdc42 activation, acting as a temporal cue. In humans, VAPB-the ortholog of Vap33-is similarly secreted in the spinal cord, and its dysregulation leads to amyotrophic lateral sclerosis type 8 (ALS8). Our findings may help inform future studies on how VAPB signaling contributes to motor circuit formation in both physiological and disease contexts.
Additional Links: PMID-41345183
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@article {pmid41345183,
year = {2025},
author = {Kamiyama, D and Kamiyama, R and Nishida, Y and Sego, A and Vining, GB and Bui, KC and Fitch, M and Do, HGT and Avraham, O and Chihara, T},
title = {The Vap33 signaling axis precisely coordinates the timing of motoneuron dendritogenesis in neural map development.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {10893},
pmid = {41345183},
issn = {2041-1723},
support = {NS107558//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; },
mesh = {Animals ; *Motor Neurons/metabolism/cytology ; *Drosophila Proteins/metabolism/genetics ; Signal Transduction ; cdc42 GTP-Binding Protein/metabolism ; Drosophila melanogaster/metabolism ; *Dendrites/metabolism ; *Neurogenesis/physiology ; Humans ; Amyotrophic Lateral Sclerosis/genetics/metabolism ; Cell Membrane/metabolism ; GTP-Binding Proteins ; },
abstract = {In Drosophila motoneurons, spatiotemporal dendritic patterns are established in the ventral nerve cord. While many guidance cues have been identified, the mechanisms of temporal regulation remain unknown. Previously, we identified the actin modulator Cdc42 GTPase as a key factor in this process. In this report, we further identify the upstream factors that activate Cdc42. Using single-cell genetics, FRET-based imaging, and biochemical techniques, we demonstrate that the guanine nucleotide exchange factor Vav is anchored to the plasma membrane via the Eph receptor tyrosine kinase, enabling Cdc42 activation. VAMP-associated protein 33 (Vap33), a potential Eph ligand supplied non-cell-autonomously, may induce Eph autophosphorylation, initiating downstream signaling. Traditionally known as an ER-resident protein, Vap33 is secreted extracellularly at the onset of Cdc42 activation, acting as a temporal cue. In humans, VAPB-the ortholog of Vap33-is similarly secreted in the spinal cord, and its dysregulation leads to amyotrophic lateral sclerosis type 8 (ALS8). Our findings may help inform future studies on how VAPB signaling contributes to motor circuit formation in both physiological and disease contexts.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Animals
*Motor Neurons/metabolism/cytology
*Drosophila Proteins/metabolism/genetics
Signal Transduction
cdc42 GTP-Binding Protein/metabolism
Drosophila melanogaster/metabolism
*Dendrites/metabolism
*Neurogenesis/physiology
Humans
Amyotrophic Lateral Sclerosis/genetics/metabolism
Cell Membrane/metabolism
GTP-Binding Proteins
RevDate: 2025-12-04
Tetramethylpyrazine nitrone: a multifaceted neuroprotective agent in neurodegenerative disorders.
Neurodegenerative disease management [Epub ahead of print].
Neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) share key pathological features, including oxidative stress, mitochondrial dysfunction, and impaired protein homeostasis, yet remain without effective disease-modifying therapies. Tetramethylpyrazine nitrone (TBN), a synthetic derivative of tetramethylpyrazine bearing a free radical-scavenging nitrone moiety, has emerged as a promising multi-target neuroprotective agent. This review synthesizes preclinical and clinical data supporting TBN's therapeutic potential in AD, PD, and ALS. In AD models, TBN reduces amyloid-β accumulation and tau hyperphosphorylation, enhances autophagic clearance, preserves synaptic integrity, and improves cognitive performance. In PD models, TBN confers dopaminergic neuroprotection, restores motor function, and promotes α-synuclein degradation, effects mediated largely through activation of the PGC-1α/Nrf2 pathway and augmentation of the ubiquitin-proteasome system (UPS). In ALS models, TBN mitigates motor neuron loss, improves motor performance, and extends survival, likely via the PGC-1α/Nrf2/HO-1 axis and enhanced autophagic activity. Phase I studies have established TBN's favorable oral and intravenous pharmacokinetics, effective blood - brain barrier penetration, and overall safety and tolerability in healthy volunteers. Owing to its multi-pathway mechanism, principally engaging antioxidant/mitochondrial pathways and proteostasis (autophagy/UPS), TBN represents a compelling candidate for continued clinical development, either as monotherapy or in combination with disease-specific interventions.
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@article {pmid41345047,
year = {2025},
author = {Bahbah, EI},
title = {Tetramethylpyrazine nitrone: a multifaceted neuroprotective agent in neurodegenerative disorders.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-15},
doi = {10.1080/17582024.2025.2598227},
pmid = {41345047},
issn = {1758-2032},
abstract = {Neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) share key pathological features, including oxidative stress, mitochondrial dysfunction, and impaired protein homeostasis, yet remain without effective disease-modifying therapies. Tetramethylpyrazine nitrone (TBN), a synthetic derivative of tetramethylpyrazine bearing a free radical-scavenging nitrone moiety, has emerged as a promising multi-target neuroprotective agent. This review synthesizes preclinical and clinical data supporting TBN's therapeutic potential in AD, PD, and ALS. In AD models, TBN reduces amyloid-β accumulation and tau hyperphosphorylation, enhances autophagic clearance, preserves synaptic integrity, and improves cognitive performance. In PD models, TBN confers dopaminergic neuroprotection, restores motor function, and promotes α-synuclein degradation, effects mediated largely through activation of the PGC-1α/Nrf2 pathway and augmentation of the ubiquitin-proteasome system (UPS). In ALS models, TBN mitigates motor neuron loss, improves motor performance, and extends survival, likely via the PGC-1α/Nrf2/HO-1 axis and enhanced autophagic activity. Phase I studies have established TBN's favorable oral and intravenous pharmacokinetics, effective blood - brain barrier penetration, and overall safety and tolerability in healthy volunteers. Owing to its multi-pathway mechanism, principally engaging antioxidant/mitochondrial pathways and proteostasis (autophagy/UPS), TBN represents a compelling candidate for continued clinical development, either as monotherapy or in combination with disease-specific interventions.},
}
RevDate: 2025-12-04
The invisible twitch: How fasciculations in ALS often go unnoticed by patients.
Additional Links: PMID-41345007
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@article {pmid41345007,
year = {2025},
author = {Marimbun, M and Nengsih, N and Saidah, S},
title = {The invisible twitch: How fasciculations in ALS often go unnoticed by patients.},
journal = {Journal of the neurological sciences},
volume = {},
number = {},
pages = {125676},
doi = {10.1016/j.jns.2025.125676},
pmid = {41345007},
issn = {1878-5883},
}
RevDate: 2025-12-04
CmpDate: 2025-12-04
Comprehensive analysis platform to understand, remedy, and eliminate amyotrophic lateral sclerosis (CAPTURE ALS): Study protocol for a Canadian multicenter, multimodal, longitudinal observational study.
PloS one, 20(12):e0332430 pii:PONE-D-24-55157.
BACKGROUND: The marked heterogeneity of Amyotrophic Lateral Sclerosis (ALS) combined with a lack of biomarkers are key contributing factors to the lack of disease-modifying treatments. The Comprehensive Analysis Platform to Understand Remedy and Eliminate ALS (CAPTURE ALS) is a Canadian platform designed to create the most comprehensive picture of people living with ALS with the objective of facilitating ALS research initiatives worldwide.
OBJECTIVES: The main aims of CAPTURE ALS include: (1) to characterize ALS and healthy controls with biosamples and data in order to provide the most comprehensive picture of individuals living with ALS to date; (2) to create a de-identified database and biosample repository linked to detailed clinical information; and (3) to develop and implement an inclusive and transparent participant engagement strategy to be active throughout all stages of CAPTURE ALS.
METHODS/RESULTS: CAPTURE ALS is a prospective, multicenter, observational, longitudinal study. People living with ALS, or a related disease and healthy controls undergo a harmonized protocol including the collection of detailed clinical information, neurological and cognitive examination, speech recording, advanced magnetic resonance imaging, and biosampling. Data and samples are stored in a biobank operating under an open science governance framework. An inclusive and transparent participant engagement strategy was designed and implemented throughout all stages of CAPTURE ALS. Four sites are operating in the consortium with a fifth being onboarded. The target enrollment is 120 affected participants and 50 controls, with the first participant visit having occurred in March 2022. Recruitment is ongoing.
DISCUSSION: CAPTURE ALS is a scalable clinical research platform that connects scientists and patients to facilitate efficient translational research. The unique and deeply phenotyped data and biosamples are a global resource towards the development of biomarkers and understanding ALS biology. This study is registered at clinicaltrials.gov (NCT: NCT05204017).
Additional Links: PMID-41343582
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@article {pmid41343582,
year = {2025},
author = {Saunders, N and Magnussen, C and Kang, H and Blais, M and Bhinder, H and Pfeffer, G and Genuis, SK and Bouvier, L and Anand, T and Abou-Haidar, R and Abrahao, A and Boivin, MN and Bowser, R and Bubela, T and Chiappini, J and Das, S and Dhanoa, A and Dupré, N and Evans, A and Ferry, N and Frater, Y and Genge, A and Graham, SJ and Greiner, R and Medina, YI and Johnston, WS and Jones, KE and Karamchandani, J and Kriz, J and Luth, W and Matte, G and Rogaeva, E and Robertson, J and Seres, P and Tam, F and Taylor, D and Tremblay-Desbiens, C and Velde, CV and Yunusova, Y and Zinman, L and Kalra, S},
title = {Comprehensive analysis platform to understand, remedy, and eliminate amyotrophic lateral sclerosis (CAPTURE ALS): Study protocol for a Canadian multicenter, multimodal, longitudinal observational study.},
journal = {PloS one},
volume = {20},
number = {12},
pages = {e0332430},
doi = {10.1371/journal.pone.0332430},
pmid = {41343582},
issn = {1932-6203},
mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/epidemiology/pathology ; Humans ; Canada/epidemiology ; Longitudinal Studies ; Prospective Studies ; Biological Specimen Banks ; Female ; Male ; Biomarkers ; },
abstract = {BACKGROUND: The marked heterogeneity of Amyotrophic Lateral Sclerosis (ALS) combined with a lack of biomarkers are key contributing factors to the lack of disease-modifying treatments. The Comprehensive Analysis Platform to Understand Remedy and Eliminate ALS (CAPTURE ALS) is a Canadian platform designed to create the most comprehensive picture of people living with ALS with the objective of facilitating ALS research initiatives worldwide.
OBJECTIVES: The main aims of CAPTURE ALS include: (1) to characterize ALS and healthy controls with biosamples and data in order to provide the most comprehensive picture of individuals living with ALS to date; (2) to create a de-identified database and biosample repository linked to detailed clinical information; and (3) to develop and implement an inclusive and transparent participant engagement strategy to be active throughout all stages of CAPTURE ALS.
METHODS/RESULTS: CAPTURE ALS is a prospective, multicenter, observational, longitudinal study. People living with ALS, or a related disease and healthy controls undergo a harmonized protocol including the collection of detailed clinical information, neurological and cognitive examination, speech recording, advanced magnetic resonance imaging, and biosampling. Data and samples are stored in a biobank operating under an open science governance framework. An inclusive and transparent participant engagement strategy was designed and implemented throughout all stages of CAPTURE ALS. Four sites are operating in the consortium with a fifth being onboarded. The target enrollment is 120 affected participants and 50 controls, with the first participant visit having occurred in March 2022. Recruitment is ongoing.
DISCUSSION: CAPTURE ALS is a scalable clinical research platform that connects scientists and patients to facilitate efficient translational research. The unique and deeply phenotyped data and biosamples are a global resource towards the development of biomarkers and understanding ALS biology. This study is registered at clinicaltrials.gov (NCT: NCT05204017).},
}
MeSH Terms:
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*Amyotrophic Lateral Sclerosis/diagnosis/epidemiology/pathology
Humans
Canada/epidemiology
Longitudinal Studies
Prospective Studies
Biological Specimen Banks
Female
Male
Biomarkers
RevDate: 2025-12-04
TDP-43 promotes efficient HSV-1 replication in human DRG-derived neurons.
Journal of virology [Epub ahead of print].
TAR DNA-binding protein 43 (TDP-43) is a versatile nuclear RNA-binding protein that performs important functions in RNA localization, processing, and stability. In the neurodegenerative disease amyotrophic lateral sclerosis (ALS) TDP-43 forms toxic, insoluble cytoplasmic aggregates that ultimately lead to neuronal loss. Although TDP-43 is expressed in every cell type, its function and subcellular localization are particularly important for neuronal homeostasis. However, it is unknown if TDP-43 has a role during herpesvirus infection. Herpes simplex virus type-1 (HSV-1), a ubiquitous neurotropic pathogen, is considered a contributing factor to neurodegenerative disorders. In this study, we tested the requirement for TDP-43 during HSV-1 infection in neuronal and non-neuronal cells. HSV-1 infection of epithelial cells and primary fibroblasts did not change overall TDP-43 abundance, nor did TDP-43 depletion detectably alter HSV-1 productive replication in a multicycle growth experiment. By contrast, when TDP-43 was depleted in neuronally-derived, differentiated HD10.6 cells, HSV-1 infectious virus production was significantly reduced in both single- and multicycle growth experiments. Notably, TDP-43 depletion restricts viral lytic gene expression at the immediate-early phase. Through nanopore direct RNA-sequencing, we uncovered enhanced intron retention in two essential viral genes-ICP0 and UL15-upon TDP-43 depletion. Thus, while depletion of TDP-43 does not detectably affect HSV-1 reproduction in epithelial cells and fibroblasts, TDP-43 is required for efficient replication in HD10.6 cells through modifying the abundance and splicing of viral mRNAs.IMPORTANCEHerpes simplex virus type-1 is a widespread neurotropic pathogen that can cause life-threatening infections of the brain and is increasingly linked to neurodegenerative disease. However, due to the lack of scalable in vitro human neuronal models or small animal models that recapitulate disease, little is known about virus-host interactions in neurons specifically. Using human epithelial cells, primary fibroblasts and a human neuron-derived cell line, we uncovered a cell type specific TDP-43 requirement for efficient HSV-1 virus replication. TDP-43 is a critical neuronal disease factor gene, and we showed it promotes HSV-1 gene expression and splicing of viral mRNAs in neuron-derived cells. This raises the possibility that targeting of TDP-43 could reveal a new antiviral strategy for severe HSV-1 infections. This work further provides valuable insights into the possible etiology of neurodegenerative disease and highlights the importance of studying virus-host interactions in relevant cell types.
Additional Links: PMID-41342556
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@article {pmid41342556,
year = {2025},
author = {Braspenning, SE and Ohnezeit, D and DeGulis, OA and Wilson, AC and Mohr, IJ},
title = {TDP-43 promotes efficient HSV-1 replication in human DRG-derived neurons.},
journal = {Journal of virology},
volume = {},
number = {},
pages = {e0091525},
doi = {10.1128/jvi.00915-25},
pmid = {41342556},
issn = {1098-5514},
abstract = {TAR DNA-binding protein 43 (TDP-43) is a versatile nuclear RNA-binding protein that performs important functions in RNA localization, processing, and stability. In the neurodegenerative disease amyotrophic lateral sclerosis (ALS) TDP-43 forms toxic, insoluble cytoplasmic aggregates that ultimately lead to neuronal loss. Although TDP-43 is expressed in every cell type, its function and subcellular localization are particularly important for neuronal homeostasis. However, it is unknown if TDP-43 has a role during herpesvirus infection. Herpes simplex virus type-1 (HSV-1), a ubiquitous neurotropic pathogen, is considered a contributing factor to neurodegenerative disorders. In this study, we tested the requirement for TDP-43 during HSV-1 infection in neuronal and non-neuronal cells. HSV-1 infection of epithelial cells and primary fibroblasts did not change overall TDP-43 abundance, nor did TDP-43 depletion detectably alter HSV-1 productive replication in a multicycle growth experiment. By contrast, when TDP-43 was depleted in neuronally-derived, differentiated HD10.6 cells, HSV-1 infectious virus production was significantly reduced in both single- and multicycle growth experiments. Notably, TDP-43 depletion restricts viral lytic gene expression at the immediate-early phase. Through nanopore direct RNA-sequencing, we uncovered enhanced intron retention in two essential viral genes-ICP0 and UL15-upon TDP-43 depletion. Thus, while depletion of TDP-43 does not detectably affect HSV-1 reproduction in epithelial cells and fibroblasts, TDP-43 is required for efficient replication in HD10.6 cells through modifying the abundance and splicing of viral mRNAs.IMPORTANCEHerpes simplex virus type-1 is a widespread neurotropic pathogen that can cause life-threatening infections of the brain and is increasingly linked to neurodegenerative disease. However, due to the lack of scalable in vitro human neuronal models or small animal models that recapitulate disease, little is known about virus-host interactions in neurons specifically. Using human epithelial cells, primary fibroblasts and a human neuron-derived cell line, we uncovered a cell type specific TDP-43 requirement for efficient HSV-1 virus replication. TDP-43 is a critical neuronal disease factor gene, and we showed it promotes HSV-1 gene expression and splicing of viral mRNAs in neuron-derived cells. This raises the possibility that targeting of TDP-43 could reveal a new antiviral strategy for severe HSV-1 infections. This work further provides valuable insights into the possible etiology of neurodegenerative disease and highlights the importance of studying virus-host interactions in relevant cell types.},
}
RevDate: 2025-12-04
Suppression of RBC alloimmunization and regulation of CD4[+]T cell dependence by C3 is not due to genetic confounders in mice.
Transfusion [Epub ahead of print].
BACKGROUND: Activation of complement protein C3 generally enhances antibody responses and C3-null mice have decreased antibody-based immunity. Mener et al. have reported a paradoxical suppressor function for C3 in alloimmunization to transfused RBCs as alloantibodies are increased in C3-null mice. Moreover, C3 regulated the CD4[+] T cell dependence of the immune response. However, the C3-null mice used were on a mixed B6/129 genetic background. We have previously reported that 129 mice have significantly higher alloimmune responses to RBC transfusion and we mapped a genetic locus that contains C3 (amongst other genes). Given the surprising nature of Mener et al.'s findings and the potential confounding from 129 genetic elements, it is a necessary part of scientific rigor to suspect that contaminating 129 elements rather than the deletion of C3 caused the observed biology.
METHODS: We used CRISPR/Cas9 to generate a new C3-null mouse (C3Cr-KO) directly in B6 mice lacking any 129 genetic elements. B6 and C3Cr-KO mice were transfused with KEL-K2med RBCs with or without CD4[+] T cell depletion and serum α-KEL IgM and Igs were quantified by crossmatch.
RESULTS: Identical to the findings of Mener et al., alloimmunization was increased in C3Cr-KO mice compared to wild-type B6 mice and CD4[+]T cell dependence of the alloimmune response was reversed.
CONCLUSIONS: The current findings eliminate a common confounder present in murine knockout systems that has caused erroneous conclusions in other settings. Both the conclusion that the presence of the C3 gene decreases RBC alloimmunization and regulates CD4[+] T cell dependence was confirmed.
Additional Links: PMID-41342465
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PubMed:
Citation:
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@article {pmid41342465,
year = {2025},
author = {Jash, A and Hay, A and Zimring, JC},
title = {Suppression of RBC alloimmunization and regulation of CD4[+]T cell dependence by C3 is not due to genetic confounders in mice.},
journal = {Transfusion},
volume = {},
number = {},
pages = {},
doi = {10.1111/trf.70026},
pmid = {41342465},
issn = {1537-2995},
support = {P01HL169552/NH/NIH HHS/United States ; },
abstract = {BACKGROUND: Activation of complement protein C3 generally enhances antibody responses and C3-null mice have decreased antibody-based immunity. Mener et al. have reported a paradoxical suppressor function for C3 in alloimmunization to transfused RBCs as alloantibodies are increased in C3-null mice. Moreover, C3 regulated the CD4[+] T cell dependence of the immune response. However, the C3-null mice used were on a mixed B6/129 genetic background. We have previously reported that 129 mice have significantly higher alloimmune responses to RBC transfusion and we mapped a genetic locus that contains C3 (amongst other genes). Given the surprising nature of Mener et al.'s findings and the potential confounding from 129 genetic elements, it is a necessary part of scientific rigor to suspect that contaminating 129 elements rather than the deletion of C3 caused the observed biology.
METHODS: We used CRISPR/Cas9 to generate a new C3-null mouse (C3Cr-KO) directly in B6 mice lacking any 129 genetic elements. B6 and C3Cr-KO mice were transfused with KEL-K2med RBCs with or without CD4[+] T cell depletion and serum α-KEL IgM and Igs were quantified by crossmatch.
RESULTS: Identical to the findings of Mener et al., alloimmunization was increased in C3Cr-KO mice compared to wild-type B6 mice and CD4[+]T cell dependence of the alloimmune response was reversed.
CONCLUSIONS: The current findings eliminate a common confounder present in murine knockout systems that has caused erroneous conclusions in other settings. Both the conclusion that the presence of the C3 gene decreases RBC alloimmunization and regulates CD4[+] T cell dependence was confirmed.},
}
RevDate: 2025-12-04
CmpDate: 2025-12-04
Are Insulin and Metformin Really Protective on Amyotrophic Lateral Sclerosis by Blocking the Astrocytic Cx43 Channel?.
Chronic diseases and translational medicine, 11(4):318-319.
Additional Links: PMID-41341745
PubMed:
Citation:
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@article {pmid41341745,
year = {2025},
author = {Finsterer, J},
title = {Are Insulin and Metformin Really Protective on Amyotrophic Lateral Sclerosis by Blocking the Astrocytic Cx43 Channel?.},
journal = {Chronic diseases and translational medicine},
volume = {11},
number = {4},
pages = {318-319},
pmid = {41341745},
issn = {2589-0514},
}
RevDate: 2025-12-04
CmpDate: 2025-12-04
C9orf72-related amyotrophic lateral sclerosis-frontotemporal dementia and links to the DNA damage response: a systematic review.
Frontiers in molecular neuroscience, 18:1671906.
The G4C2 repeat expansion in C9orf72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). While healthy individuals have fewer than 30 repeats, affected patients may carry hundreds to thousands. This expansion accounts for approximately 40% of familial ALS and 25% of familial FTD cases, and between 5 and 10% cases of sporadic ALS and FTD. Three overlapping pathological mechanisms have been proposed for the C9orf72 expansion: loss of function due to protein deficiency, gain of function through RNA foci, and the production of toxic dipeptide repeat proteins (DPRs) via repeat-associated non-ATG (RAN) translation. This systematic review investigates the role of DNA damage in C9orf72-related ALS-FTD. Analysis of twelve peer-reviewed studies showed that C9orf72 repeat expansions and DPRs compromise genome stability across four experimental models: human cell lines, induced pluripotent stem cell-derived neurons, rodent neurons, and postmortem tissue. We identified four mechanisms underlying DNA damage accumulation: disruption of the ATM pathway, impairment of DNA repair efficiency, formation of R-loops, and mitochondrial dysfunction with oxidative stress. In addition, several consequences of DNA damage were identified, including misrepair-mediated repeat expansion and activation of STING pathway. These findings highlight the key role of DNA damage in C9orf72-related pathology. Consistent with this, targeting DNA damage response factors extended lifespan and improved motor function in mouse models. This review highlights the contribution of DNA damage to C9orf72 pathology and suggest new therapeutic avenues, including personalized approaches based on genetic background.
Additional Links: PMID-41341655
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Citation:
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@article {pmid41341655,
year = {2025},
author = {Almalki, S and Salama, M and Taylor, MJ and Ahmed, Z and Tuxworth, RI},
title = {C9orf72-related amyotrophic lateral sclerosis-frontotemporal dementia and links to the DNA damage response: a systematic review.},
journal = {Frontiers in molecular neuroscience},
volume = {18},
number = {},
pages = {1671906},
pmid = {41341655},
issn = {1662-5099},
abstract = {The G4C2 repeat expansion in C9orf72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). While healthy individuals have fewer than 30 repeats, affected patients may carry hundreds to thousands. This expansion accounts for approximately 40% of familial ALS and 25% of familial FTD cases, and between 5 and 10% cases of sporadic ALS and FTD. Three overlapping pathological mechanisms have been proposed for the C9orf72 expansion: loss of function due to protein deficiency, gain of function through RNA foci, and the production of toxic dipeptide repeat proteins (DPRs) via repeat-associated non-ATG (RAN) translation. This systematic review investigates the role of DNA damage in C9orf72-related ALS-FTD. Analysis of twelve peer-reviewed studies showed that C9orf72 repeat expansions and DPRs compromise genome stability across four experimental models: human cell lines, induced pluripotent stem cell-derived neurons, rodent neurons, and postmortem tissue. We identified four mechanisms underlying DNA damage accumulation: disruption of the ATM pathway, impairment of DNA repair efficiency, formation of R-loops, and mitochondrial dysfunction with oxidative stress. In addition, several consequences of DNA damage were identified, including misrepair-mediated repeat expansion and activation of STING pathway. These findings highlight the key role of DNA damage in C9orf72-related pathology. Consistent with this, targeting DNA damage response factors extended lifespan and improved motor function in mouse models. This review highlights the contribution of DNA damage to C9orf72 pathology and suggest new therapeutic avenues, including personalized approaches based on genetic background.},
}
RevDate: 2025-12-04
CmpDate: 2025-12-04
Receptor-mediated mitophagy: a new target of neurodegenerative diseases.
Frontiers in neurology, 16:1665315.
Neurodegenerative diseases are a category of neurological conditions with high prevalence that pose major treatment challenges. Common pathologies involve protein accumulation and mitochondrial damage. Mitophagy maintains cellular homeostasis by removing defective mitochondria, which are associated with the pathogenesis of neurodegenerative diseases. Although the ubiquitin-dependent mitophagy mediated by the PINK1-Parkin pathway has been extensively studied, growing evidence indicates that receptor-mediated mitophagy plays a crucial compensatory role in neurons, particularly when the PINK1-Parkin pathway is impaired. This review focuses on the emerging field of receptor-mediated mitophagy, systematically elaborating its role as a key homeostatic mechanism operating independently of the canonical PINK1/Parkin pathway. It provides a focused analysis of the specific functions and activation mechanisms of key receptors-including BNIP3, NIX, FUNDC1, and AMBRA1-in models of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Furthermore, this review explores the clinical potential of targeting these specific receptors for precise intervention, aiming to provide a new theoretical foundation and direction for developing therapeutic strategies against neurodegenerative diseases.
Additional Links: PMID-41341510
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Citation:
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@article {pmid41341510,
year = {2025},
author = {Yang, J and Yang, F and Chen, G and Liu, M and Yuan, S and Zhang, TE},
title = {Receptor-mediated mitophagy: a new target of neurodegenerative diseases.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1665315},
pmid = {41341510},
issn = {1664-2295},
abstract = {Neurodegenerative diseases are a category of neurological conditions with high prevalence that pose major treatment challenges. Common pathologies involve protein accumulation and mitochondrial damage. Mitophagy maintains cellular homeostasis by removing defective mitochondria, which are associated with the pathogenesis of neurodegenerative diseases. Although the ubiquitin-dependent mitophagy mediated by the PINK1-Parkin pathway has been extensively studied, growing evidence indicates that receptor-mediated mitophagy plays a crucial compensatory role in neurons, particularly when the PINK1-Parkin pathway is impaired. This review focuses on the emerging field of receptor-mediated mitophagy, systematically elaborating its role as a key homeostatic mechanism operating independently of the canonical PINK1/Parkin pathway. It provides a focused analysis of the specific functions and activation mechanisms of key receptors-including BNIP3, NIX, FUNDC1, and AMBRA1-in models of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Furthermore, this review explores the clinical potential of targeting these specific receptors for precise intervention, aiming to provide a new theoretical foundation and direction for developing therapeutic strategies against neurodegenerative diseases.},
}
RevDate: 2025-12-04
CmpDate: 2025-12-04
Exploring Speech Biosignatures for Traumatic Brain Injury and Neurodegeneration: Pilot Machine Learning Study.
JMIR neurotechnology, 4:e64624.
BACKGROUND: Speech features are increasingly linked to neurodegenerative and mental health conditions, offering the potential for early detection and differentiation between disorders. As interest in speech analysis grows, distinguishing between conditions becomes critical for reliable diagnosis and assessment.
OBJECTIVE: This pilot study explores speech biosignatures in two distinct neurodegenerative conditions: (1) mild traumatic brain injuries (eg, concussions) and (2) Parkinson disease (PD) as the neurodegenerative condition.
METHODS: The study included speech samples from 235 participants (97 concussed and 94 age-matched healthy controls, 29 PD and 15 healthy controls) for the PaTaKa test and 239 participants (91 concussed and 104 healthy controls, 29 PD and 15 healthy controls) for the Sustained Vowel (/ah/) test. Age-matched healthy controls were used. Young age-matched controls were used for concussion and respective age-matched controls for neurodegenerative participants (15 healthy samples for both tests). Data augmentation with noise was applied to balance small datasets for neurodegenerative and healthy controls. Machine learning models (support vector machine, decision tree, random forest, and Extreme Gradient Boosting) were employed using 37 temporal and spectral speech features. A 5-fold stratified cross-validation was used to evaluate classification performance.
RESULTS: For the PaTaKa test, classifiers performed well, achieving F 1-scores above 0.9 for concussed versus healthy and concussed versus neurodegenerative classifications across all models. Initial tests using the original dataset for neurodegenerative versus healthy classification yielded very poor results, with F 1-scores below 0.2 and accuracy under 30% (eg, below 12 out of 44 correctly classified samples) across all models. This underscored the need for data augmentation, which significantly improved performance to 60%-70% (eg, 26-31 out of 44 samples) accuracy. In contrast, the Sustained Vowel test showed mixed results; F 1-scores remained high (more than 0.85 across all models) for concussed versus neurodegenerative classifications but were significantly lower for concussed versus healthy (0.59-0.62) and neurodegenerative versus healthy (0.33-0.77), depending on the model.
CONCLUSIONS: This study highlights the potential of speech features as biomarkers for neurodegenerative conditions. The PaTaKa test exhibited strong discriminative ability, especially for concussed versus neurodegenerative and concussed versus healthy tasks, whereas challenges remain for neurodegenerative versus healthy classification. These findings emphasize the need for further exploration of speech-based tools for differential diagnosis and early identification in neurodegenerative health.
Additional Links: PMID-41341425
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Citation:
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@article {pmid41341425,
year = {2025},
author = {Rubaiat, R and Templeton, JM and Schneider, SL and De Silva, U and Madanian, S and Poellabauer, C},
title = {Exploring Speech Biosignatures for Traumatic Brain Injury and Neurodegeneration: Pilot Machine Learning Study.},
journal = {JMIR neurotechnology},
volume = {4},
number = {},
pages = {e64624},
pmid = {41341425},
issn = {2817-092X},
abstract = {BACKGROUND: Speech features are increasingly linked to neurodegenerative and mental health conditions, offering the potential for early detection and differentiation between disorders. As interest in speech analysis grows, distinguishing between conditions becomes critical for reliable diagnosis and assessment.
OBJECTIVE: This pilot study explores speech biosignatures in two distinct neurodegenerative conditions: (1) mild traumatic brain injuries (eg, concussions) and (2) Parkinson disease (PD) as the neurodegenerative condition.
METHODS: The study included speech samples from 235 participants (97 concussed and 94 age-matched healthy controls, 29 PD and 15 healthy controls) for the PaTaKa test and 239 participants (91 concussed and 104 healthy controls, 29 PD and 15 healthy controls) for the Sustained Vowel (/ah/) test. Age-matched healthy controls were used. Young age-matched controls were used for concussion and respective age-matched controls for neurodegenerative participants (15 healthy samples for both tests). Data augmentation with noise was applied to balance small datasets for neurodegenerative and healthy controls. Machine learning models (support vector machine, decision tree, random forest, and Extreme Gradient Boosting) were employed using 37 temporal and spectral speech features. A 5-fold stratified cross-validation was used to evaluate classification performance.
RESULTS: For the PaTaKa test, classifiers performed well, achieving F 1-scores above 0.9 for concussed versus healthy and concussed versus neurodegenerative classifications across all models. Initial tests using the original dataset for neurodegenerative versus healthy classification yielded very poor results, with F 1-scores below 0.2 and accuracy under 30% (eg, below 12 out of 44 correctly classified samples) across all models. This underscored the need for data augmentation, which significantly improved performance to 60%-70% (eg, 26-31 out of 44 samples) accuracy. In contrast, the Sustained Vowel test showed mixed results; F 1-scores remained high (more than 0.85 across all models) for concussed versus neurodegenerative classifications but were significantly lower for concussed versus healthy (0.59-0.62) and neurodegenerative versus healthy (0.33-0.77), depending on the model.
CONCLUSIONS: This study highlights the potential of speech features as biomarkers for neurodegenerative conditions. The PaTaKa test exhibited strong discriminative ability, especially for concussed versus neurodegenerative and concussed versus healthy tasks, whereas challenges remain for neurodegenerative versus healthy classification. These findings emphasize the need for further exploration of speech-based tools for differential diagnosis and early identification in neurodegenerative health.},
}
RevDate: 2025-12-04
CmpDate: 2025-12-04
Twenty-Five Years of AI in Neurology: The Journey of Predictive Medicine and Biological Breakthroughs.
JMIR neurotechnology, 3:e59556.
Neurological disorders are the leading cause of physical and cognitive disability across the globe, currently affecting up to 15% of the world population, with the burden of chronic neurodegenerative diseases having doubled over the last 2 decades. Two decades ago, neurologists relying solely on clinical signs and basic imaging faced challenges in diagnosis and treatment. Today, the integration of artificial intelligence (AI) and bioinformatic methods is changing this landscape. This paper explores this transformative journey, emphasizing the critical role of AI in neurology, aiming to integrate a multitude of methods and thereby enhance the field of neurology. Over the past 25 years, integrating biomedical data science into medicine, particularly neurology, has fundamentally transformed how we understand, diagnose, and treat neurological diseases. Advances in genomics sequencing, the introduction of new imaging methods, the discovery of novel molecular biomarkers for nervous system function, a comprehensive understanding of immunology and neuroimmunology shaping disease subtypes, and the advent of advanced electrophysiological recording methods, alongside the digitalization of medical records and the rise of AI, all led to an unparalleled surge in data within neurology. In addition, telemedicine and web-based interactive health platforms, accelerated by the COVID-19 pandemic, have become integral to neurology practice. The real-world impact of these advancements is evident, with AI-driven analysis of imaging and genetic data leading to earlier and more accurate diagnoses of conditions such as multiple sclerosis, Parkinson disease, amyotrophic lateral sclerosis, Alzheimer disease, and more. Neuroinformatics is the key component connecting all these advances. By harnessing the power of IT and computational methods to efficiently organize, analyze, and interpret vast datasets, we can extract meaningful insights from complex neurological data, contributing to a deeper understanding of the intricate workings of the brain. In this paper, we describe the large-scale datasets that have emerged in neurology over the last 25 years and showcase the major advancements made by integrating these datasets with advanced neuroinformatic approaches for the diagnosis and treatment of neurological disorders. We further discuss challenges in integrating AI into neurology, including ethical considerations in data use, the need for further personalization of treatment, and embracing new emerging technologies like quantum computing. These developments are shaping a future where neurological care is more precise, accessible, and tailored to individual patient needs. We believe further advancements in AI will bridge traditional medical disciplines and cutting-edge technology, navigating the complexities of neurological data and steering medicine toward a future of more precise, accessible, and patient-centric health care.
Additional Links: PMID-41341242
PubMed:
Citation:
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@article {pmid41341242,
year = {2024},
author = {Gutman, B and Shmilovitch, AH and Aran, D and Shelly, S},
title = {Twenty-Five Years of AI in Neurology: The Journey of Predictive Medicine and Biological Breakthroughs.},
journal = {JMIR neurotechnology},
volume = {3},
number = {},
pages = {e59556},
pmid = {41341242},
issn = {2817-092X},
abstract = {Neurological disorders are the leading cause of physical and cognitive disability across the globe, currently affecting up to 15% of the world population, with the burden of chronic neurodegenerative diseases having doubled over the last 2 decades. Two decades ago, neurologists relying solely on clinical signs and basic imaging faced challenges in diagnosis and treatment. Today, the integration of artificial intelligence (AI) and bioinformatic methods is changing this landscape. This paper explores this transformative journey, emphasizing the critical role of AI in neurology, aiming to integrate a multitude of methods and thereby enhance the field of neurology. Over the past 25 years, integrating biomedical data science into medicine, particularly neurology, has fundamentally transformed how we understand, diagnose, and treat neurological diseases. Advances in genomics sequencing, the introduction of new imaging methods, the discovery of novel molecular biomarkers for nervous system function, a comprehensive understanding of immunology and neuroimmunology shaping disease subtypes, and the advent of advanced electrophysiological recording methods, alongside the digitalization of medical records and the rise of AI, all led to an unparalleled surge in data within neurology. In addition, telemedicine and web-based interactive health platforms, accelerated by the COVID-19 pandemic, have become integral to neurology practice. The real-world impact of these advancements is evident, with AI-driven analysis of imaging and genetic data leading to earlier and more accurate diagnoses of conditions such as multiple sclerosis, Parkinson disease, amyotrophic lateral sclerosis, Alzheimer disease, and more. Neuroinformatics is the key component connecting all these advances. By harnessing the power of IT and computational methods to efficiently organize, analyze, and interpret vast datasets, we can extract meaningful insights from complex neurological data, contributing to a deeper understanding of the intricate workings of the brain. In this paper, we describe the large-scale datasets that have emerged in neurology over the last 25 years and showcase the major advancements made by integrating these datasets with advanced neuroinformatic approaches for the diagnosis and treatment of neurological disorders. We further discuss challenges in integrating AI into neurology, including ethical considerations in data use, the need for further personalization of treatment, and embracing new emerging technologies like quantum computing. These developments are shaping a future where neurological care is more precise, accessible, and tailored to individual patient needs. We believe further advancements in AI will bridge traditional medical disciplines and cutting-edge technology, navigating the complexities of neurological data and steering medicine toward a future of more precise, accessible, and patient-centric health care.},
}
RevDate: 2025-12-04
CmpDate: 2025-12-04
A Live-Cell NanoBRET Assay to Monitor RNA-Protein Interactions and Their Inhibition by Small Molecules.
ACS central science, 11(11):2154-2171.
RNA-protein interactions are critical for cellular processes, including translation, pre-mRNA splicing, post-transcriptional modifications, and RNA stability. Their dysregulation is implicated in diseases such as myotonic dystrophy type 1 (DM1) and amyotrophic lateral sclerosis (ALS). To investigate RNA-protein interactions, here is described a live-cell NanoBioluminescence Resonance Energy Transfer (NanoBRET) assay to study the interaction between expanded r-(CUG) repeats [r-(CUG)[exp]] and muscleblind-like 1 (MBNL1), central to DM1 pathogenesis. This r-(CUG)[exp] sequesters MBNL1, a regulator of alternative pre-mRNA splicing, in nuclear foci causing splicing dysregulation. In the NanoBRET assay, r-(CUG)[exp] acts as a scaffold to bring into proximity a BRET pair, MBNL1-NanoLuciferase (NanoLuc) and MBNL1-HaloTag, enabling a quantitative readout of RNA-protein interactions. Following assay optimization, an RNA-focused small molecule library was screened, identifying ten compounds with shared chemotypes that disrupt the r-(CUG)[exp]-MBNL1 complex. Nuclear magnetic resonance (NMR) studies revealed these inhibitors bind to the 1 × 1 UU internal loops formed when r-(CUG)[exp] folds. Five of these molecules rescued two cellular hallmarks of DM1 in patient-derived myotubes, alternative pre-mRNA splicing defects and formation of nuclear r-(CUG)/MBNL1-positive foci. These results demonstrate that the NanoBRET assay is a powerful tool to study RNA-protein interactions in live cells and to identify small molecules that alleviate RNA-mediated cellular pathology.
Additional Links: PMID-41341060
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@article {pmid41341060,
year = {2025},
author = {Shan, J and Taghavi, A and Caine, EA and Sekioka, R and Rajchin, V and Burke, JM and Watkins, JM and Childs-Disney, JL and Disney, MD},
title = {A Live-Cell NanoBRET Assay to Monitor RNA-Protein Interactions and Their Inhibition by Small Molecules.},
journal = {ACS central science},
volume = {11},
number = {11},
pages = {2154-2171},
pmid = {41341060},
issn = {2374-7943},
abstract = {RNA-protein interactions are critical for cellular processes, including translation, pre-mRNA splicing, post-transcriptional modifications, and RNA stability. Their dysregulation is implicated in diseases such as myotonic dystrophy type 1 (DM1) and amyotrophic lateral sclerosis (ALS). To investigate RNA-protein interactions, here is described a live-cell NanoBioluminescence Resonance Energy Transfer (NanoBRET) assay to study the interaction between expanded r-(CUG) repeats [r-(CUG)[exp]] and muscleblind-like 1 (MBNL1), central to DM1 pathogenesis. This r-(CUG)[exp] sequesters MBNL1, a regulator of alternative pre-mRNA splicing, in nuclear foci causing splicing dysregulation. In the NanoBRET assay, r-(CUG)[exp] acts as a scaffold to bring into proximity a BRET pair, MBNL1-NanoLuciferase (NanoLuc) and MBNL1-HaloTag, enabling a quantitative readout of RNA-protein interactions. Following assay optimization, an RNA-focused small molecule library was screened, identifying ten compounds with shared chemotypes that disrupt the r-(CUG)[exp]-MBNL1 complex. Nuclear magnetic resonance (NMR) studies revealed these inhibitors bind to the 1 × 1 UU internal loops formed when r-(CUG)[exp] folds. Five of these molecules rescued two cellular hallmarks of DM1 in patient-derived myotubes, alternative pre-mRNA splicing defects and formation of nuclear r-(CUG)/MBNL1-positive foci. These results demonstrate that the NanoBRET assay is a powerful tool to study RNA-protein interactions in live cells and to identify small molecules that alleviate RNA-mediated cellular pathology.},
}
RevDate: 2025-12-03
Contribution of comorbid pathologies to amyotrophic lateral sclerosis with cognitive or behavioral abnormalities.
BMC neurology pii:10.1186/s12883-025-04556-z [Epub ahead of print].
BACKGROUND: Amyotrophic lateral sclerosis (ALS) often presents with cognitive or behavioral abnormalities. The cortical involvement of TAR DNA-binding protein-43 (TDP-43) pathology is considered a major cause of these abnormalities. However, the contribution of underlying comorbid pathologies remains unclear.
METHODS: We investigated the clinicopathological characteristics of 29 autopsy cases of ALS with cognitive or behavioral abnormalities and evaluated the association between clinical symptoms and comorbid pathologies such as Alzheimer's disease (AD), argyrophilic grain disease (AGD), dementia with Lewy bodies (DLB), and primary age-related tauopathy (PART), as well as the presence of cortical TDP-43 pathology.
RESULTS: Of the 29 patients, 17 exhibited comorbid pathologies (AD, AGD, or PART), which may contribute to cognitive or behavioral abnormalities. None of the cases met the pathological criteria for DLB. The group with comorbid pathologies was significantly older, but clinical symptoms did not differ between the groups. Behavioral abnormalities and memory impairment were frequently observed in both groups. All six subjects without cortical TDP-43 pathology had comorbid pathologies, which had a notable effect on cognitive or behavioral abnormalities. Hippocampal sclerosis and memory impairment were observed in ALS cases without comorbid pathologies.
CONCLUSION: A high frequency of comorbid pathologies is observed in elderly patients with ALS presenting with cognitive or behavioral abnormalities. There are cases of ALS in which comorbid pathologies such as AD, AGD, and PART may contribute to cognitive or behavioral abnormalities, even in the absence of cortical TDP-43 pathology. Hippocampal sclerosis of ALS may contribute to memory impairment independently of comorbid pathologies.
Additional Links: PMID-41339846
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@article {pmid41339846,
year = {2025},
author = {Moriyoshi, H and Akagi, A and Riku, Y and Sone, J and Miyahara, H and Yoshida, M and Katsuno, M and Iwasaki, Y},
title = {Contribution of comorbid pathologies to amyotrophic lateral sclerosis with cognitive or behavioral abnormalities.},
journal = {BMC neurology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12883-025-04556-z},
pmid = {41339846},
issn = {1471-2377},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) often presents with cognitive or behavioral abnormalities. The cortical involvement of TAR DNA-binding protein-43 (TDP-43) pathology is considered a major cause of these abnormalities. However, the contribution of underlying comorbid pathologies remains unclear.
METHODS: We investigated the clinicopathological characteristics of 29 autopsy cases of ALS with cognitive or behavioral abnormalities and evaluated the association between clinical symptoms and comorbid pathologies such as Alzheimer's disease (AD), argyrophilic grain disease (AGD), dementia with Lewy bodies (DLB), and primary age-related tauopathy (PART), as well as the presence of cortical TDP-43 pathology.
RESULTS: Of the 29 patients, 17 exhibited comorbid pathologies (AD, AGD, or PART), which may contribute to cognitive or behavioral abnormalities. None of the cases met the pathological criteria for DLB. The group with comorbid pathologies was significantly older, but clinical symptoms did not differ between the groups. Behavioral abnormalities and memory impairment were frequently observed in both groups. All six subjects without cortical TDP-43 pathology had comorbid pathologies, which had a notable effect on cognitive or behavioral abnormalities. Hippocampal sclerosis and memory impairment were observed in ALS cases without comorbid pathologies.
CONCLUSION: A high frequency of comorbid pathologies is observed in elderly patients with ALS presenting with cognitive or behavioral abnormalities. There are cases of ALS in which comorbid pathologies such as AD, AGD, and PART may contribute to cognitive or behavioral abnormalities, even in the absence of cortical TDP-43 pathology. Hippocampal sclerosis of ALS may contribute to memory impairment independently of comorbid pathologies.},
}
RevDate: 2025-12-03
Insights and considerations on predicting cognitive and behavioral disturbances in MND with pure motor onset.
This commentary discusses the study by Bicaj et al., which examines baseline predictors of cognitive and behavioral disturbances (C/BI) in motor neuron diseases (MNDs) with pure motor onset. The study's longitudinal design and use of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) provide valuable insights into extramotor progression in MNDs. While the study offers important findings, including potential predictors such as age at onset and specific ECAS scores, it is limited by sample size and potential biases. Suggestions for future research include larger multicenter studies, incorporating biomarkers, and addressing confounding factors to refine risk stratification and clinical management of MND.
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@article {pmid41339165,
year = {2025},
author = {Wang, Y and Zhang, Q},
title = {Insights and considerations on predicting cognitive and behavioral disturbances in MND with pure motor onset.},
journal = {Journal of the neurological sciences},
volume = {},
number = {},
pages = {125673},
doi = {10.1016/j.jns.2025.125673},
pmid = {41339165},
issn = {1878-5883},
abstract = {This commentary discusses the study by Bicaj et al., which examines baseline predictors of cognitive and behavioral disturbances (C/BI) in motor neuron diseases (MNDs) with pure motor onset. The study's longitudinal design and use of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) provide valuable insights into extramotor progression in MNDs. While the study offers important findings, including potential predictors such as age at onset and specific ECAS scores, it is limited by sample size and potential biases. Suggestions for future research include larger multicenter studies, incorporating biomarkers, and addressing confounding factors to refine risk stratification and clinical management of MND.},
}
RevDate: 2025-12-03
CmpDate: 2025-12-03
VAPB is a negative regulator of STING-mediated innate immune signaling.
Science advances, 11(49):eaea3996.
Stimulator of IFN genes (STING) is an endoplasmic reticulum (ER) signaling receptor involved in the type I interferon response to pathogen- or self-derived cytosolic double-stranded DNA. Excessive activation of STING is associated with many diseases, but the regulatory mechanism of STING activation remains to be further elucidated. Here, we identify VAPB as a negative regulator of STING-mediated innate immune response. VAPB deficiency increases the expression of type I interferons under resting conditions or upon stimulation. Mechanistically, VAPB associates and translocates with STING, thereby regulating STING translocation, oligomerization, and recruitment of TBK1. In vivo, deficiency of VAPB enhances the expression of type I interferons and prevents lethality following HSV-1 infection. Furthermore, VAPB P56S, a pathogenic mutation causing amyotrophic lateral sclerosis (ALS), can promote STING-mediated innate immune response under resting conditions, which might contribute to further understanding of the relationship between cGAS-STING pathway and ALS. Our study identifies VAPB as a critical regulating factor in cGAS-STING-mediated innate immune responses.
Additional Links: PMID-41337593
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@article {pmid41337593,
year = {2025},
author = {Ji, W and Zhang, Y and Zhang, L and Liu, Q and Niu, S and Feng, Y and Chen, F and Liu, X and Li, X},
title = {VAPB is a negative regulator of STING-mediated innate immune signaling.},
journal = {Science advances},
volume = {11},
number = {49},
pages = {eaea3996},
doi = {10.1126/sciadv.aea3996},
pmid = {41337593},
issn = {2375-2548},
mesh = {*Membrane Proteins/metabolism/genetics ; *Immunity, Innate ; *Signal Transduction ; Animals ; Humans ; Mice ; *Vesicular Transport Proteins/genetics/metabolism ; Herpesvirus 1, Human/immunology ; Amyotrophic Lateral Sclerosis/genetics ; Interferon Type I/metabolism/genetics ; HEK293 Cells ; Herpes Simplex/immunology/virology/genetics ; Protein Serine-Threonine Kinases/metabolism ; },
abstract = {Stimulator of IFN genes (STING) is an endoplasmic reticulum (ER) signaling receptor involved in the type I interferon response to pathogen- or self-derived cytosolic double-stranded DNA. Excessive activation of STING is associated with many diseases, but the regulatory mechanism of STING activation remains to be further elucidated. Here, we identify VAPB as a negative regulator of STING-mediated innate immune response. VAPB deficiency increases the expression of type I interferons under resting conditions or upon stimulation. Mechanistically, VAPB associates and translocates with STING, thereby regulating STING translocation, oligomerization, and recruitment of TBK1. In vivo, deficiency of VAPB enhances the expression of type I interferons and prevents lethality following HSV-1 infection. Furthermore, VAPB P56S, a pathogenic mutation causing amyotrophic lateral sclerosis (ALS), can promote STING-mediated innate immune response under resting conditions, which might contribute to further understanding of the relationship between cGAS-STING pathway and ALS. Our study identifies VAPB as a critical regulating factor in cGAS-STING-mediated innate immune responses.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
*Membrane Proteins/metabolism/genetics
*Immunity, Innate
*Signal Transduction
Animals
Humans
Mice
*Vesicular Transport Proteins/genetics/metabolism
Herpesvirus 1, Human/immunology
Amyotrophic Lateral Sclerosis/genetics
Interferon Type I/metabolism/genetics
HEK293 Cells
Herpes Simplex/immunology/virology/genetics
Protein Serine-Threonine Kinases/metabolism
RevDate: 2025-12-03
CmpDate: 2025-12-03
Detection of Amyotrophic Lateral Sclerosis with Computer Audition: An Impact Analysis of Different Speech Tasks.
Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference, 2025:1-5.
We investigate the performance difference between training generic and task-based systems for the automatic detection of patients with Amyotrophic Lateral Sclerosis (ALS) from speech. We exploit the paralinguistic information embedded in their speech while producing the sustained vowel /a:/, repeating the syllables /da/-/da/ and /da/-/ba/ - separately -, reading a text passage, and describing a picture. While the former system consists of a single model, the latter is composed of five task-dedicated models, each one in charge of processing the speech samples corresponding to each task. We also analyse the performance of each task-dedicated model individually. We conduct our experiments on the novel, German-speaking AIMnd dataset. The obtained results - assessed in terms of the Unweighted Average Recall (UAR) - indicate that the task-based systems outperform the generic ones in two out of the four scenarios explored. The generic system only outperforms the task-based system in one scenario. In terms of the task-dedicated models, the SVClinear-based classifier exploiting the extended Geneva Minimalistic Acoustic Parameter Set (eGeMAPS) extracted from the sustained vowel /a:/ production task yields the best performance on the Test set with a UAR of 92%.
Additional Links: PMID-41337107
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@article {pmid41337107,
year = {2025},
author = {Mallol-Ragolta, A and Gonzalez-Machorro, M and von Heynitz, R and Scherzer, K and Cordts, I and Schuller, B},
title = {Detection of Amyotrophic Lateral Sclerosis with Computer Audition: An Impact Analysis of Different Speech Tasks.},
journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference},
volume = {2025},
number = {},
pages = {1-5},
doi = {10.1109/EMBC58623.2025.11254090},
pmid = {41337107},
issn = {2694-0604},
mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/physiopathology ; Humans ; *Speech ; },
abstract = {We investigate the performance difference between training generic and task-based systems for the automatic detection of patients with Amyotrophic Lateral Sclerosis (ALS) from speech. We exploit the paralinguistic information embedded in their speech while producing the sustained vowel /a:/, repeating the syllables /da/-/da/ and /da/-/ba/ - separately -, reading a text passage, and describing a picture. While the former system consists of a single model, the latter is composed of five task-dedicated models, each one in charge of processing the speech samples corresponding to each task. We also analyse the performance of each task-dedicated model individually. We conduct our experiments on the novel, German-speaking AIMnd dataset. The obtained results - assessed in terms of the Unweighted Average Recall (UAR) - indicate that the task-based systems outperform the generic ones in two out of the four scenarios explored. The generic system only outperforms the task-based system in one scenario. In terms of the task-dedicated models, the SVClinear-based classifier exploiting the extended Geneva Minimalistic Acoustic Parameter Set (eGeMAPS) extracted from the sustained vowel /a:/ production task yields the best performance on the Test set with a UAR of 92%.},
}
MeSH Terms:
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*Amyotrophic Lateral Sclerosis/diagnosis/physiopathology
Humans
*Speech
RevDate: 2025-12-03
CmpDate: 2025-12-03
Predicting Motor Intent from Residual Neck Muscle Activity in Individuals with Neck Weakness from ALS.
Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference, 2025:1-6.
The long-term goal of this work is to restore dexterous and intuitive head-neck motion to patients with Amyotrophic Lateral Sclerosis (ALS). ALS is an idiopathic disease characterized by progressive paralysis. Some patients experience neck weakness such that their heads permanently drop to their chests, causing pain and extreme difficulty eating, navigating, and socializing. We previously developed the Utah Neck Exoskeleton, a powered neck brace that supports the head and uses electric motors to move the head in a large range of motion, counteracting head drop. However, the exoskeleton has been controlled either with a joystick or gaze tracking, both of which are difficult to use for parts of the ALS population. Here, we show that the residual neck muscles of ALS patients with neck weakness can be used to determine intended neck position and motion. Electromyographic (EMG) signals were recorded from the neck muscles of two individuals with ALS, low clinical functional scores, and self-reported neck weakness. EMG was then mapped to either steady-state head position or the direction of head motion using convolutional neural networks. Despite the patients having neck weakness and limited range of motion, EMG signals were sufficient to accurately classify both steady-state head position and the direction of head motion (97.1% and 83.12% median accuracy, respectively). As such, this work demonstrates that EMG may serve as a dexterous and intuitive control modality for real-time head-neck movement, and in conjunction with the Utah Neck Exoskeleton, may ultimately improve quality of life for individuals with head drop.Clinical RelevanceResidual neck muscle activity in ALS patients can be recorded via surface EMG and potentially used to reliably predict intended head position and motion.
Additional Links: PMID-41336973
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@article {pmid41336973,
year = {2025},
author = {Buczak, MK and Brignone, J and Cole, KM and Caden Hamrick, W and Bromberg, MB and Zhang, H and George, JA},
title = {Predicting Motor Intent from Residual Neck Muscle Activity in Individuals with Neck Weakness from ALS.},
journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference},
volume = {2025},
number = {},
pages = {1-6},
doi = {10.1109/EMBC58623.2025.11253699},
pmid = {41336973},
issn = {2694-0604},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology ; *Neck Muscles/physiopathology ; Electromyography ; Male ; Middle Aged ; *Muscle Weakness/physiopathology ; Female ; },
abstract = {The long-term goal of this work is to restore dexterous and intuitive head-neck motion to patients with Amyotrophic Lateral Sclerosis (ALS). ALS is an idiopathic disease characterized by progressive paralysis. Some patients experience neck weakness such that their heads permanently drop to their chests, causing pain and extreme difficulty eating, navigating, and socializing. We previously developed the Utah Neck Exoskeleton, a powered neck brace that supports the head and uses electric motors to move the head in a large range of motion, counteracting head drop. However, the exoskeleton has been controlled either with a joystick or gaze tracking, both of which are difficult to use for parts of the ALS population. Here, we show that the residual neck muscles of ALS patients with neck weakness can be used to determine intended neck position and motion. Electromyographic (EMG) signals were recorded from the neck muscles of two individuals with ALS, low clinical functional scores, and self-reported neck weakness. EMG was then mapped to either steady-state head position or the direction of head motion using convolutional neural networks. Despite the patients having neck weakness and limited range of motion, EMG signals were sufficient to accurately classify both steady-state head position and the direction of head motion (97.1% and 83.12% median accuracy, respectively). As such, this work demonstrates that EMG may serve as a dexterous and intuitive control modality for real-time head-neck movement, and in conjunction with the Utah Neck Exoskeleton, may ultimately improve quality of life for individuals with head drop.Clinical RelevanceResidual neck muscle activity in ALS patients can be recorded via surface EMG and potentially used to reliably predict intended head position and motion.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*Amyotrophic Lateral Sclerosis/physiopathology
*Neck Muscles/physiopathology
Electromyography
Male
Middle Aged
*Muscle Weakness/physiopathology
Female
RevDate: 2025-12-03
CmpDate: 2025-12-03
Mastering Tongue-Computer Interfaces: A Pilot Study on How Users Improve With Practice.
Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference, 2025:1-6.
Tongue-operated input devices allow people with motor disabilities to interact with technology and their environment. Many such devices use barbell piercings to track the position of the tongue. Recent developments in tongue-computer interfacing have led to the proposal of a frame-integrated tracer that is not attached to the user's tongue. This study sought to investigate how an individuals ability to use their tongue to manipulate an integrated tracer evolves through use. Five people without motor disabilities and seven people with motor disabilities used a non-invasive inductive tongue-computer interface over six and three sessions, respectively. Among the individuals with motor disabilities were five people with spinal cord injury (SCI) and two men with amyotrophic lateral sclerosis (ALS). Their performance was evaluated at the start of each session using an intraoral target selection task. The participants with no motor disabilities showed a 26% improvement in median target selection time and a 15% improvement in median success rate. The median success rate for subjects with SCI improved by 40%, but the median target selection time stayed constant. Meanwhile, one participant with ALS increased his speed, while the other saw no substantial improvement. Furthermore, compared to the participants without disabilities, the participants with motor disabilities had a higher tendency to select the wrong target. Our findings provide further evidence that repeated use of a tongue-operated input device increases intraoral target selection speed and accuracy. Participants with motor disabilities may require longer dwell times to avoid unintentionally selecting targets when they move the activation unit.
Additional Links: PMID-41336792
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@article {pmid41336792,
year = {2025},
author = {Santos Cardoso, AS and Kaseler, RL and Ammitzboll, AL and Hagen, EM and Blicher, J and Obal, I and Kirtas, O and Khan, JS and Mohammadi, M and Jochumsen, M and Andreasen Struijk, LNS},
title = {Mastering Tongue-Computer Interfaces: A Pilot Study on How Users Improve With Practice.},
journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference},
volume = {2025},
number = {},
pages = {1-6},
doi = {10.1109/EMBC58623.2025.11251588},
pmid = {41336792},
issn = {2694-0604},
mesh = {Humans ; *Tongue/physiology ; Male ; Pilot Projects ; Adult ; *User-Computer Interface ; Middle Aged ; Amyotrophic Lateral Sclerosis/physiopathology/rehabilitation ; Spinal Cord Injuries/physiopathology/rehabilitation ; Female ; },
abstract = {Tongue-operated input devices allow people with motor disabilities to interact with technology and their environment. Many such devices use barbell piercings to track the position of the tongue. Recent developments in tongue-computer interfacing have led to the proposal of a frame-integrated tracer that is not attached to the user's tongue. This study sought to investigate how an individuals ability to use their tongue to manipulate an integrated tracer evolves through use. Five people without motor disabilities and seven people with motor disabilities used a non-invasive inductive tongue-computer interface over six and three sessions, respectively. Among the individuals with motor disabilities were five people with spinal cord injury (SCI) and two men with amyotrophic lateral sclerosis (ALS). Their performance was evaluated at the start of each session using an intraoral target selection task. The participants with no motor disabilities showed a 26% improvement in median target selection time and a 15% improvement in median success rate. The median success rate for subjects with SCI improved by 40%, but the median target selection time stayed constant. Meanwhile, one participant with ALS increased his speed, while the other saw no substantial improvement. Furthermore, compared to the participants without disabilities, the participants with motor disabilities had a higher tendency to select the wrong target. Our findings provide further evidence that repeated use of a tongue-operated input device increases intraoral target selection speed and accuracy. Participants with motor disabilities may require longer dwell times to avoid unintentionally selecting targets when they move the activation unit.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*Tongue/physiology
Male
Pilot Projects
Adult
*User-Computer Interface
Middle Aged
Amyotrophic Lateral Sclerosis/physiopathology/rehabilitation
Spinal Cord Injuries/physiopathology/rehabilitation
Female
RevDate: 2025-12-03
CmpDate: 2025-12-03
iEMG-Based Diagnosis of ALS and Myopathy using 1D-CNN.
Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference, 2025:1-5.
Amyotrophic Lateral Sclerosis (ALS) and myopathy are debilitating neuromuscular disorders that require accurate and timely diagnosis for effective management. Traditional electromyography (EMG)-based diagnostic methods rely on manual interpretation, which is time-consuming and prone to variability. This study proposes an approach that directly classifies EMG signals using a one-dimensional convolutional neural network (1D-CNN) without feature extraction, addressing the limitations of existing methods that depend on handcrafted features and focus primarily on binary classification. The proposed model is evaluated on a publicly available EMG dataset, achieving an overall accuracy of 99.27%, with macro and weighted precision, recall, and F1-scores exceeding 99% across ALS, myopathy, and healthy subjects. Unlike previous approaches that require extensive preprocessing, our method maintains high classification performance while reducing computational complexity, offering a clinically relevant multiclass classification framework. Although our method achieves high classification performance, it also maintains a strong balance between sensitivity and specificity, ensuring reliable and accurate neuromuscular disorder diagnosis, making it a practical tool for clinical applications. Future research will focus on improving model generalizability, expanding dataset diversity, and integrating real-time deployment for enhanced diagnostic utility.
Additional Links: PMID-41336481
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PubMed:
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@article {pmid41336481,
year = {2025},
author = {Sid'El Moctar, SM and Nasrallah, C and Rida, I and Boudaoud, S},
title = {iEMG-Based Diagnosis of ALS and Myopathy using 1D-CNN.},
journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference},
volume = {2025},
number = {},
pages = {1-5},
doi = {10.1109/EMBC58623.2025.11251693},
pmid = {41336481},
issn = {2694-0604},
mesh = {*Amyotrophic Lateral Sclerosis/diagnosis/physiopathology ; Humans ; *Electromyography/methods ; *Neural Networks, Computer ; *Muscular Diseases/diagnosis/physiopathology ; Algorithms ; Signal Processing, Computer-Assisted ; Sensitivity and Specificity ; *Diagnosis, Computer-Assisted/methods ; },
abstract = {Amyotrophic Lateral Sclerosis (ALS) and myopathy are debilitating neuromuscular disorders that require accurate and timely diagnosis for effective management. Traditional electromyography (EMG)-based diagnostic methods rely on manual interpretation, which is time-consuming and prone to variability. This study proposes an approach that directly classifies EMG signals using a one-dimensional convolutional neural network (1D-CNN) without feature extraction, addressing the limitations of existing methods that depend on handcrafted features and focus primarily on binary classification. The proposed model is evaluated on a publicly available EMG dataset, achieving an overall accuracy of 99.27%, with macro and weighted precision, recall, and F1-scores exceeding 99% across ALS, myopathy, and healthy subjects. Unlike previous approaches that require extensive preprocessing, our method maintains high classification performance while reducing computational complexity, offering a clinically relevant multiclass classification framework. Although our method achieves high classification performance, it also maintains a strong balance between sensitivity and specificity, ensuring reliable and accurate neuromuscular disorder diagnosis, making it a practical tool for clinical applications. Future research will focus on improving model generalizability, expanding dataset diversity, and integrating real-time deployment for enhanced diagnostic utility.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
*Amyotrophic Lateral Sclerosis/diagnosis/physiopathology
Humans
*Electromyography/methods
*Neural Networks, Computer
*Muscular Diseases/diagnosis/physiopathology
Algorithms
Signal Processing, Computer-Assisted
Sensitivity and Specificity
*Diagnosis, Computer-Assisted/methods
RevDate: 2025-12-03
CmpDate: 2025-12-03
Wrist Range of Motion Variability for Adaptive Exoskeleton Design: A Study on users with and without SCI or ALS.
Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference, 2025:1-6.
Wrist exoskeletons hold promise for assisting individuals with motor impairments such as spinal cord injury (SCI) and amyotrophic lateral sclerosis (ALS). However, existing designs often lack adjustability and adaptability to the individual wrist range of motion (ROM), which is crucial for safety and usability. This study presents a literature review of the wrist abduction/adduction ROM measurements in individuals without motor disability and individuals with motor impairments and highlights on the measurement details and findings. This study also investigates wrist abduction/adduction ROM in three user groups: fifteen individuals without any motor disability, two individuals with ALS, and five with SCI. The experimental procedure included the completion of three trials, where ROM was measured and analyzed to determine intergroup variability. Individuals without motor disability exhibited the largest ROM range, while SCI users had reduced adduction. Our findings highlight the need for user-specific ROM considerations in exoskeleton design to optimize functionality and prevent discomfort or injury. This study contributes to the development of adjustable and user-centered wrist exoskeletons, addressing safety and usability gaps in the current state of the art.Clinical Relevance- The observed ROM differences between users with and without disabilities underscore the importance of tailoring exoskeletons to specific user needs, emphasizing the role of variability as a critical factor in rehabilitation.
Additional Links: PMID-41336457
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PubMed:
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@article {pmid41336457,
year = {2025},
author = {Khan, JS and Mohammadi, M and Ammitzboll, AL and Hagen, EM and Blicher, J and Obal, I and Cardoso, ASS and Kirtas, O and Kaseler, RL and Rasmussen, J and Struijk, LNSA},
title = {Wrist Range of Motion Variability for Adaptive Exoskeleton Design: A Study on users with and without SCI or ALS.},
journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference},
volume = {2025},
number = {},
pages = {1-6},
doi = {10.1109/EMBC58623.2025.11251763},
pmid = {41336457},
issn = {2694-0604},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology ; *Exoskeleton Device ; *Range of Motion, Articular ; *Spinal Cord Injuries/physiopathology/rehabilitation ; Male ; Middle Aged ; *Wrist/physiopathology ; Female ; Equipment Design ; Adult ; },
abstract = {Wrist exoskeletons hold promise for assisting individuals with motor impairments such as spinal cord injury (SCI) and amyotrophic lateral sclerosis (ALS). However, existing designs often lack adjustability and adaptability to the individual wrist range of motion (ROM), which is crucial for safety and usability. This study presents a literature review of the wrist abduction/adduction ROM measurements in individuals without motor disability and individuals with motor impairments and highlights on the measurement details and findings. This study also investigates wrist abduction/adduction ROM in three user groups: fifteen individuals without any motor disability, two individuals with ALS, and five with SCI. The experimental procedure included the completion of three trials, where ROM was measured and analyzed to determine intergroup variability. Individuals without motor disability exhibited the largest ROM range, while SCI users had reduced adduction. Our findings highlight the need for user-specific ROM considerations in exoskeleton design to optimize functionality and prevent discomfort or injury. This study contributes to the development of adjustable and user-centered wrist exoskeletons, addressing safety and usability gaps in the current state of the art.Clinical Relevance- The observed ROM differences between users with and without disabilities underscore the importance of tailoring exoskeletons to specific user needs, emphasizing the role of variability as a critical factor in rehabilitation.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*Amyotrophic Lateral Sclerosis/physiopathology
*Exoskeleton Device
*Range of Motion, Articular
*Spinal Cord Injuries/physiopathology/rehabilitation
Male
Middle Aged
*Wrist/physiopathology
Female
Equipment Design
Adult
RevDate: 2025-12-03
CmpDate: 2025-12-03
ChatBCI-4-ALS: A High-Performance, LLM-Driven, Intent-Based BCI Communication System for Individuals with ALS.
Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference, 2025:1-6.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that leads to significant motor and speech impairments, increasing the need for alternative means of communication to support quality of life. P300 speller brain computer interfaces (BCIs) have shown promise in facilitating non-muscular communication by detecting P300 event-related potentials (ERPs) in response to visual stimuli. However, these systems are generally slow and can not fully address the communication needs of ALS patients, specially, when the primary goal is to convey intent with minimal cognitive load. In this paper, we present ChatBCI-4-ALS, the first intent-based BCI communication system designed for individuals with ALS. ChatBCI-4-ALS leverages large language models (LLMs) and employs a dynamic flash algorithm to enhance typing speed, and enable efficient communication of the user's intent beyond exact lexical matches. Additionally, we introduce new semantic-based quantitative performance metrics to evaluate the effectiveness of intent-based communication. Results from online experiments suggest that ChatBCI-4-ALS achieves record-breaking average spelling speed of 23.87 char/min (with the best case scenario of 42.16 char/min), and a best information transfer rate (ITR) of 128.85 bits/min, marking an advancement in P300 BCI-based communication systems.
Additional Links: PMID-41336280
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PubMed:
Citation:
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@article {pmid41336280,
year = {2025},
author = {Hong, J and Rao, P and Wang, W and Chen, S and Najafizadeh, L},
title = {ChatBCI-4-ALS: A High-Performance, LLM-Driven, Intent-Based BCI Communication System for Individuals with ALS.},
journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference},
volume = {2025},
number = {},
pages = {1-6},
doi = {10.1109/EMBC58623.2025.11253329},
pmid = {41336280},
issn = {2694-0604},
mesh = {*Amyotrophic Lateral Sclerosis/physiopathology ; Humans ; *Brain-Computer Interfaces ; Algorithms ; *Communication Devices for People with Disabilities ; Electroencephalography ; Event-Related Potentials, P300 ; Language ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that leads to significant motor and speech impairments, increasing the need for alternative means of communication to support quality of life. P300 speller brain computer interfaces (BCIs) have shown promise in facilitating non-muscular communication by detecting P300 event-related potentials (ERPs) in response to visual stimuli. However, these systems are generally slow and can not fully address the communication needs of ALS patients, specially, when the primary goal is to convey intent with minimal cognitive load. In this paper, we present ChatBCI-4-ALS, the first intent-based BCI communication system designed for individuals with ALS. ChatBCI-4-ALS leverages large language models (LLMs) and employs a dynamic flash algorithm to enhance typing speed, and enable efficient communication of the user's intent beyond exact lexical matches. Additionally, we introduce new semantic-based quantitative performance metrics to evaluate the effectiveness of intent-based communication. Results from online experiments suggest that ChatBCI-4-ALS achieves record-breaking average spelling speed of 23.87 char/min (with the best case scenario of 42.16 char/min), and a best information transfer rate (ITR) of 128.85 bits/min, marking an advancement in P300 BCI-based communication systems.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
*Amyotrophic Lateral Sclerosis/physiopathology
Humans
*Brain-Computer Interfaces
Algorithms
*Communication Devices for People with Disabilities
Electroencephalography
Event-Related Potentials, P300
Language
RevDate: 2025-12-03
CmpDate: 2025-12-03
A Novel Approach to Improve SSVEP-BCI Performance Through Neurofeedback Training.
Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference, 2025:1-6.
Brain-Computer interface (BCI), which translates neural activities into commands for external devices, holds significant promise for clinical rehabilitation and assisted movement for individuals with motor disabilities. Among various BCI paradigms, the steady-state visual evoked potential (SSVEP) based BCI garnered considerable attention due to its relatively stable and high-speed communication capabilities. However, a notable portion of the population, referred to as BCI illiteracy, struggles to effectively control BCI systems due to their inability to generate or modulate the neural patterns required for interaction. To address this issue, we proposed a user-centered approach using neurofeedback training (NFT) to improve individual's performance on SSVEP-BCI. As a result, after a five-day training period, significant improvements in SSVEP-BCI performance were only observed in the training group rather than the control group without training. Notably, some subjects initially determined as BCI-illiterate also gained effective control of the BCI system after training. Further analysis revealed that the improvement of SSVEP-BCI performance had a close link with increased power and inter-trial phase coherence of the SSVEP response, indicating that NFT successfully strengthened the user's task-related neural responses. These findings highlight the potential of NFT as a user-centered intervention to improve BCI control performance, offering a promising pathway to address BCI illiteracy and promote the broader application of BCI systems.Clinical Relevance- This study proposes an effective approach to enhancing the controllability of SSVEP-BCI systems, addressing the critical issue of individual control limitations. The developed method demonstrates significant clinical potential for promoting SSVEP-BCI applications, particularly in facilitating communication and device control for patients with severe motor impairments, such as amyotrophic lateral sclerosis (ALS) and locked-in syndrome (LIS).
Additional Links: PMID-41335863
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PubMed:
Citation:
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@article {pmid41335863,
year = {2025},
author = {Li, M and Yao, Y and Dong, B and Wang, K and Yu, H and Xu, M and Ming, D},
title = {A Novel Approach to Improve SSVEP-BCI Performance Through Neurofeedback Training.},
journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference},
volume = {2025},
number = {},
pages = {1-6},
doi = {10.1109/EMBC58623.2025.11254803},
pmid = {41335863},
issn = {2694-0604},
mesh = {Humans ; *Brain-Computer Interfaces ; *Neurofeedback/methods ; *Evoked Potentials, Visual/physiology ; Male ; Adult ; Electroencephalography ; Female ; },
abstract = {Brain-Computer interface (BCI), which translates neural activities into commands for external devices, holds significant promise for clinical rehabilitation and assisted movement for individuals with motor disabilities. Among various BCI paradigms, the steady-state visual evoked potential (SSVEP) based BCI garnered considerable attention due to its relatively stable and high-speed communication capabilities. However, a notable portion of the population, referred to as BCI illiteracy, struggles to effectively control BCI systems due to their inability to generate or modulate the neural patterns required for interaction. To address this issue, we proposed a user-centered approach using neurofeedback training (NFT) to improve individual's performance on SSVEP-BCI. As a result, after a five-day training period, significant improvements in SSVEP-BCI performance were only observed in the training group rather than the control group without training. Notably, some subjects initially determined as BCI-illiterate also gained effective control of the BCI system after training. Further analysis revealed that the improvement of SSVEP-BCI performance had a close link with increased power and inter-trial phase coherence of the SSVEP response, indicating that NFT successfully strengthened the user's task-related neural responses. These findings highlight the potential of NFT as a user-centered intervention to improve BCI control performance, offering a promising pathway to address BCI illiteracy and promote the broader application of BCI systems.Clinical Relevance- This study proposes an effective approach to enhancing the controllability of SSVEP-BCI systems, addressing the critical issue of individual control limitations. The developed method demonstrates significant clinical potential for promoting SSVEP-BCI applications, particularly in facilitating communication and device control for patients with severe motor impairments, such as amyotrophic lateral sclerosis (ALS) and locked-in syndrome (LIS).},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
Humans
*Brain-Computer Interfaces
*Neurofeedback/methods
*Evoked Potentials, Visual/physiology
Male
Adult
Electroencephalography
Female
RevDate: 2025-12-03
CmpDate: 2025-12-03
Robotic Arm: Assistive Technology for Independent Feeding.
Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference, 2025:1-5.
Disabilities, such as those caused by spinal cord injury, stroke, cerebral palsy, amyotrophic lateral sclerosis and amputations, can impair upper limb function and limit eating autonomy, requiring third-party assistance. Thus, assistive technologies have emerged as viable alternatives for promoting greater independence and social inclusion. This article presents the development of an educational robotic arm with 5 degrees of freedom for use as a meal-assist robot. A 3D printer was used for the utensils and wood for the base. To receive user commands, a voice recognition module was implemented to identify the five programmed commands. To verify the effectiveness of the proposed method, several tests were conducted, including a water transfer test and execution time measurement. The assistive device successfully transported more than 75% of the water and completed each feeding cycle in 21 s, demonstrating its effectiveness in aiding the feeding process.
Additional Links: PMID-41335671
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PubMed:
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@article {pmid41335671,
year = {2025},
author = {Petrikic, D and Dos Santos, RFF and Sipoli, GV and Santos, KMM and Nogueira Neto, GN and Nohama, P},
title = {Robotic Arm: Assistive Technology for Independent Feeding.},
journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference},
volume = {2025},
number = {},
pages = {1-5},
doi = {10.1109/EMBC58623.2025.11253161},
pmid = {41335671},
issn = {2694-0604},
mesh = {*Robotics/instrumentation ; Humans ; *Self-Help Devices ; Equipment Design ; },
abstract = {Disabilities, such as those caused by spinal cord injury, stroke, cerebral palsy, amyotrophic lateral sclerosis and amputations, can impair upper limb function and limit eating autonomy, requiring third-party assistance. Thus, assistive technologies have emerged as viable alternatives for promoting greater independence and social inclusion. This article presents the development of an educational robotic arm with 5 degrees of freedom for use as a meal-assist robot. A 3D printer was used for the utensils and wood for the base. To receive user commands, a voice recognition module was implemented to identify the five programmed commands. To verify the effectiveness of the proposed method, several tests were conducted, including a water transfer test and execution time measurement. The assistive device successfully transported more than 75% of the water and completed each feeding cycle in 21 s, demonstrating its effectiveness in aiding the feeding process.},
}
MeSH Terms:
show MeSH Terms
hide MeSH Terms
*Robotics/instrumentation
Humans
*Self-Help Devices
Equipment Design
RevDate: 2025-12-03
Novel in-frame duplication variant of SOD1 in a Japanese family with familial amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis & frontotemporal degeneration [Epub ahead of print].
OBJECTIVES: To analyze the cases of a family with a novel in-frame duplication variant (NM_000454.5:c.357_357 + 2dup, p.Val120dup) of SOD1 and a structural model of the mutated SOD1 protein.
METHODS: The clinical profiles of three patients in the family were analyzed, including the neuropathological findings of the proband's mother. Genetic analyses were conducted for three patients. cDNA and in silico structural analyses were performed to evaluate the effects of duplication variants on the structure of SOD1.
RESULTS: The clinical features of the patients included predominant involvement of the lower motor neurons, asymmetric onset of motor symptoms in the lower limbs, and a relatively rapid progression of muscular weakness and respiratory insufficiency. Neuropathological findings revealed severe loss of spinal cord motor neurons, and immunohistochemistry using an anti-misfolded SOD1 antibody revealed aggregates in the spinal cord. Genetic analyses revealed a c.357_357 + 2dup at the exon 4-intron 4 boundary of SOD1 in three patients. cDNA analysis of the proband suggested the presence of a valine (p.Val120dup) duplication in the heterozygous state, and the SOD1 transcript level showed no significant differences from those of healthy controls. In silico structural analyses predicted that p.Val120dup could affect the structure of the β-barrels and copper ion binding site of SOD1, suggesting an abnormal conformation of SOD1 that is predicted to interfere with the binding of copper ions.
CONCLUSION: We identified a novel in-frame duplication variant in the C-terminus of β7 of SOD1. This genotype-structure-phenotype study of SOD1 provides valuable insights into disease-causing mechanisms.
Additional Links: PMID-41334676
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PubMed:
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@article {pmid41334676,
year = {2025},
author = {Nakajima, M and Naruse, H and Riku, Y and Ueda, K and Matsukawa, T and Mitsui, J and Nakamura, Y and Ishida, S and Yamada, T and Moro, N and Kotsuki, N and Nagai, K and Tokushige, SI and Uchibori, A and Oishi, C and Yabata, H and Urushitani, M and Iwasaki, Y and Ishiura, H and Toda, T and Tsuji, S and Ichikawa, Y},
title = {Novel in-frame duplication variant of SOD1 in a Japanese family with familial amyotrophic lateral sclerosis.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-11},
doi = {10.1080/21678421.2025.2593302},
pmid = {41334676},
issn = {2167-9223},
abstract = {OBJECTIVES: To analyze the cases of a family with a novel in-frame duplication variant (NM_000454.5:c.357_357 + 2dup, p.Val120dup) of SOD1 and a structural model of the mutated SOD1 protein.
METHODS: The clinical profiles of three patients in the family were analyzed, including the neuropathological findings of the proband's mother. Genetic analyses were conducted for three patients. cDNA and in silico structural analyses were performed to evaluate the effects of duplication variants on the structure of SOD1.
RESULTS: The clinical features of the patients included predominant involvement of the lower motor neurons, asymmetric onset of motor symptoms in the lower limbs, and a relatively rapid progression of muscular weakness and respiratory insufficiency. Neuropathological findings revealed severe loss of spinal cord motor neurons, and immunohistochemistry using an anti-misfolded SOD1 antibody revealed aggregates in the spinal cord. Genetic analyses revealed a c.357_357 + 2dup at the exon 4-intron 4 boundary of SOD1 in three patients. cDNA analysis of the proband suggested the presence of a valine (p.Val120dup) duplication in the heterozygous state, and the SOD1 transcript level showed no significant differences from those of healthy controls. In silico structural analyses predicted that p.Val120dup could affect the structure of the β-barrels and copper ion binding site of SOD1, suggesting an abnormal conformation of SOD1 that is predicted to interfere with the binding of copper ions.
CONCLUSION: We identified a novel in-frame duplication variant in the C-terminus of β7 of SOD1. This genotype-structure-phenotype study of SOD1 provides valuable insights into disease-causing mechanisms.},
}
RevDate: 2025-12-03
SIGMAR1 gene-related neuromuscular disorders - what do we know?.
Neurologia i neurochirurgia polska pii:VM/OJS/J/106304 [Epub ahead of print].
INTRODUCTION: Distal hereditary motor neuropathies (dHMNs) are a clinically and genetically diverse group of rare neuromuscular disorders characterized by progressive distal muscle weakness and atrophy, often with early onset and sparing of sensory function. One subtype, Jerash-type dHMN (dHMNJ), is caused by biallelic mutations in the SIGMAR1 gene and presents with pyramidal signs in addition to distal weakness.
MATERIAL AND METHODS: A literature review was conducted by searches of the MEDLINE and PubMed databases using selected terms. Relevant original articles, case reports, case series, and reviews were selected as data sources.
DISCUSSION: SIGMAR1-related disorders (SIGMAR1-RD) encompass a broad clinical spectrum including dHMN and juvenile amyotrophic lateral sclerosis (ALS) phenotypes. The Sigma-1 receptor plays a key role in cellular stress responses, ER-mitochondria interaction, and neuronal survival. Clinical presentation often includes distal muscle weakness and atrophy with pyramidal signs.
We present a 12-year-old boy with distal muscle weakness, foot drop, and pyramidal signs. Genetic testing identified a homozygous c.247T>C (p.Phe83Leu) SIGMAR1 variant, previously classified as a variant of uncertain significance (VUS).
CONCLUSION: This article supports the pathogenicity of the c.247T>C (p.Phe83Leu) SIGMAR1 variant and underlines the need for broader genetic testing in hereditary motor neuropathies.
Additional Links: PMID-41334667
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PubMed:
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@article {pmid41334667,
year = {2025},
author = {Kalita, M and Jędrzejowska, M and Potulska-Chromik, A and Aragon-Gawińska, K and Franaszczyk, M and Stokłosa, T and Lipowska, M and Kostera-Pruszczyk, A},
title = {SIGMAR1 gene-related neuromuscular disorders - what do we know?.},
journal = {Neurologia i neurochirurgia polska},
volume = {},
number = {},
pages = {},
doi = {10.5603/pjnns.106304},
pmid = {41334667},
issn = {0028-3843},
abstract = {INTRODUCTION: Distal hereditary motor neuropathies (dHMNs) are a clinically and genetically diverse group of rare neuromuscular disorders characterized by progressive distal muscle weakness and atrophy, often with early onset and sparing of sensory function. One subtype, Jerash-type dHMN (dHMNJ), is caused by biallelic mutations in the SIGMAR1 gene and presents with pyramidal signs in addition to distal weakness.
MATERIAL AND METHODS: A literature review was conducted by searches of the MEDLINE and PubMed databases using selected terms. Relevant original articles, case reports, case series, and reviews were selected as data sources.
DISCUSSION: SIGMAR1-related disorders (SIGMAR1-RD) encompass a broad clinical spectrum including dHMN and juvenile amyotrophic lateral sclerosis (ALS) phenotypes. The Sigma-1 receptor plays a key role in cellular stress responses, ER-mitochondria interaction, and neuronal survival. Clinical presentation often includes distal muscle weakness and atrophy with pyramidal signs.
We present a 12-year-old boy with distal muscle weakness, foot drop, and pyramidal signs. Genetic testing identified a homozygous c.247T>C (p.Phe83Leu) SIGMAR1 variant, previously classified as a variant of uncertain significance (VUS).
CONCLUSION: This article supports the pathogenicity of the c.247T>C (p.Phe83Leu) SIGMAR1 variant and underlines the need for broader genetic testing in hereditary motor neuropathies.},
}
RevDate: 2025-12-03
Loss of Nuclear TDP-43 Impairs Lipid Metabolism in Microglia-Like Cells.
Research square pii:rs.3.rs-8036170.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease marked by progressive motor neuron loss, with TDP-43 pathology present in over 90% of cases. While neuroinflammation is a recognized hallmark, the role of microglia in ALS pathogenesis remains incompletely understood. Here, we demonstrate that TDP-43 regulates microglial function via triglyceride metabolism. Using shRNA-mediated TARDBP knockdown in human monocyte-derived microglia-like cells (MDMi), we observed suppressed cholesterol biosynthesis, upregulated fatty acid uptake, lipid droplet accumulation, enhanced phagocytic activity, and increased IL-1β production. Inhibiting diacylglycerol acyltransferase (DGAT) enzymes reduced lipid droplet formation, phagocytosis, and IL-1β, directly linking the triglyceride pathway to microglial activation. Patient-derived MDMi from both sporadic and TARDBP -mutant ALS cases showed overlapping as well as distinct alterations, some of which were reversed by DGAT inhibition. Our findings identify dysregulated triglyceride metabolism as a novel pathway through which TDP-43 mediates microglial dysfunction, highlighting a potential therapeutic target for ALS.
Additional Links: PMID-41333389
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@article {pmid41333389,
year = {2025},
author = {Kabra, K and Dressman, D and Talcoff, R and Yidenk, M and Rifai, OM and Hoover, BN and Shneider, NA and Elyaman, W and Area-Gomez, E and Bradshaw, EM},
title = {Loss of Nuclear TDP-43 Impairs Lipid Metabolism in Microglia-Like Cells.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-8036170/v1},
pmid = {41333389},
issn = {2693-5015},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease marked by progressive motor neuron loss, with TDP-43 pathology present in over 90% of cases. While neuroinflammation is a recognized hallmark, the role of microglia in ALS pathogenesis remains incompletely understood. Here, we demonstrate that TDP-43 regulates microglial function via triglyceride metabolism. Using shRNA-mediated TARDBP knockdown in human monocyte-derived microglia-like cells (MDMi), we observed suppressed cholesterol biosynthesis, upregulated fatty acid uptake, lipid droplet accumulation, enhanced phagocytic activity, and increased IL-1β production. Inhibiting diacylglycerol acyltransferase (DGAT) enzymes reduced lipid droplet formation, phagocytosis, and IL-1β, directly linking the triglyceride pathway to microglial activation. Patient-derived MDMi from both sporadic and TARDBP -mutant ALS cases showed overlapping as well as distinct alterations, some of which were reversed by DGAT inhibition. Our findings identify dysregulated triglyceride metabolism as a novel pathway through which TDP-43 mediates microglial dysfunction, highlighting a potential therapeutic target for ALS.},
}
RevDate: 2025-12-03
Building and sustaining trust across communities: Lessons from a large-scale, community-based cancer needs assessment in New York City.
medRxiv : the preprint server for health sciences pii:2025.11.20.25340674.
BACKGROUND: Trust is central to healthcare engagement yet remains underexamined in the context of large-scale community needs assessments. The Cancer Community Health Resources and Needs Assessment (Cancer CHRNA) was developed and implemented to identify multilevel determinants for cancer prevention and disparities; and examine the structural and system levels factors influencing healthcare access and prevention behaviors across populations represented in New York City. This study examines how trust emerged as a dominant theme and the relational and technical strategies community health workers (CHWs) and community-based organizations (CBOs) used to establish and sustain trust during survey implementation.
METHODS: Cancer CHRNA was implemented in community- and clinic-settings in nine languages: English, Arabic, Bangla, Chinese-Simplified/Traditional, Haitian-Creole, Korean, Spanish, Russian, and Urdu by bicultural and bilingual CHWs, in partnership with a network of CBOs. This qualitative process evaluation draws on data from CHW interviews, field notes, and a research team focus group. Analysis was guided by the Consolidated Framework for Implementation Research (CFIR), with secondary coding informed by Metz et al.'s theoretical model for trusting relationships, which distinguishes relational and technical strategies of trust-building.
RESULTS: Three overarching themes related to trust emerged: 1) CHWs as trusted messengers embodying trustworthiness; 2) the role of CBO partnerships in enhancing trust; and 3) the development of sustained trust with both CBOs and community members. Across these themes, CHWs and CBOs employed relational strategies (authenticity, empathy, bi-directional communication, vulnerability) and technical strategies (cultural and linguistic concordance, demonstration of expertise, frequent interactions, responsiveness). These strategies activated trust, which in turn enabled successful recruitment and sustained engagement.
CONCLUSION: To our knowledge, Cancer CHRNA is the first needs assessment to assess cancer behavioral and social priorities in nine languages, providing a unique exploration of the role of trust within such an assessment. Findings demonstrate that culturally and linguistically concordant CHWs, working in partnership with trusted CBOs, were central to fostering trust across the relational and technical strategies of trust building and facilitating broad community participation. By highlighting trust as the mechanism underpinning recruitment success, this study offers practical insights for designing future multilingual, community-based assessments.
Additional Links: PMID-41332877
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@article {pmid41332877,
year = {2025},
author = {Rakhra, A and Yusuf, Y and Min, D and Foster, V and Sifuentes, S and Kazmi, A and Kwon, SC},
title = {Building and sustaining trust across communities: Lessons from a large-scale, community-based cancer needs assessment in New York City.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.11.20.25340674},
pmid = {41332877},
abstract = {BACKGROUND: Trust is central to healthcare engagement yet remains underexamined in the context of large-scale community needs assessments. The Cancer Community Health Resources and Needs Assessment (Cancer CHRNA) was developed and implemented to identify multilevel determinants for cancer prevention and disparities; and examine the structural and system levels factors influencing healthcare access and prevention behaviors across populations represented in New York City. This study examines how trust emerged as a dominant theme and the relational and technical strategies community health workers (CHWs) and community-based organizations (CBOs) used to establish and sustain trust during survey implementation.
METHODS: Cancer CHRNA was implemented in community- and clinic-settings in nine languages: English, Arabic, Bangla, Chinese-Simplified/Traditional, Haitian-Creole, Korean, Spanish, Russian, and Urdu by bicultural and bilingual CHWs, in partnership with a network of CBOs. This qualitative process evaluation draws on data from CHW interviews, field notes, and a research team focus group. Analysis was guided by the Consolidated Framework for Implementation Research (CFIR), with secondary coding informed by Metz et al.'s theoretical model for trusting relationships, which distinguishes relational and technical strategies of trust-building.
RESULTS: Three overarching themes related to trust emerged: 1) CHWs as trusted messengers embodying trustworthiness; 2) the role of CBO partnerships in enhancing trust; and 3) the development of sustained trust with both CBOs and community members. Across these themes, CHWs and CBOs employed relational strategies (authenticity, empathy, bi-directional communication, vulnerability) and technical strategies (cultural and linguistic concordance, demonstration of expertise, frequent interactions, responsiveness). These strategies activated trust, which in turn enabled successful recruitment and sustained engagement.
CONCLUSION: To our knowledge, Cancer CHRNA is the first needs assessment to assess cancer behavioral and social priorities in nine languages, providing a unique exploration of the role of trust within such an assessment. Findings demonstrate that culturally and linguistically concordant CHWs, working in partnership with trusted CBOs, were central to fostering trust across the relational and technical strategies of trust building and facilitating broad community participation. By highlighting trust as the mechanism underpinning recruitment success, this study offers practical insights for designing future multilingual, community-based assessments.},
}
RevDate: 2025-12-03
Artificial Intelligence Approximates Human Affect Ratings of Cannabis Images.
medRxiv : the preprint server for health sciences pii:2025.11.14.25339699.
Cannabis imagery is proliferating online and can elicit affective responses related to use. Scalable tools are needed to evaluate how this proliferation could influence population health. This pilot study tested whether multimodal generative artificial intelligence (MGAI) can reproduce subjective human affect ratings of cannabis images. Four MGAI agents (model: gpt-4o-2024-11-20) were created to parallel the four human participant subgroups from Macatee et al. 2021, defined by primary method of cannabis administration (bong, bowl, joint/blunt, vaporizer). Using Macatee et al.'s participant instructions and standardized image set, each agent rated images of its primary method of administration on valence, arousal, and urge constructs. For each image-construct pair, n=100 ratings were generated in separate conversational threads using zero-shot prompting. Image-level MGAI mean ratings were compared with human mean ratings using Two One-Sided Tests of equivalence and Spearman correlations. Although formal statistical equivalence was rare (4% valence, 11% arousal, 3% urge), MGAI ratings approximated human ratings closely (Mean difference of mean ratings = - 0.31, SD = 1.23) and correlations between MGAI and human mean ratings were moderate to high: r s (valence) = 0.55, r s (arousal) = 0.34, r s (urge) = 0.56. MGAI also reproduced the parabolic relation between rating means and standard deviations observed in human data. These preliminary results indicate that MGAI can approximate human cannabis cue-reactivity patterns closely enough to justify continued refinement. MGAI could potentially be developed into a Cannabis Regulatory Science tool to aid regulatory oversight of online cannabis marketing.
Additional Links: PMID-41332875
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@article {pmid41332875,
year = {2025},
author = {Borodovsky, JT and Macatee, RJ and Preum, SM and Chung, CL and Malone, P and Gonzalez-Marquez, DP},
title = {Artificial Intelligence Approximates Human Affect Ratings of Cannabis Images.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.11.14.25339699},
pmid = {41332875},
abstract = {Cannabis imagery is proliferating online and can elicit affective responses related to use. Scalable tools are needed to evaluate how this proliferation could influence population health. This pilot study tested whether multimodal generative artificial intelligence (MGAI) can reproduce subjective human affect ratings of cannabis images. Four MGAI agents (model: gpt-4o-2024-11-20) were created to parallel the four human participant subgroups from Macatee et al. 2021, defined by primary method of cannabis administration (bong, bowl, joint/blunt, vaporizer). Using Macatee et al.'s participant instructions and standardized image set, each agent rated images of its primary method of administration on valence, arousal, and urge constructs. For each image-construct pair, n=100 ratings were generated in separate conversational threads using zero-shot prompting. Image-level MGAI mean ratings were compared with human mean ratings using Two One-Sided Tests of equivalence and Spearman correlations. Although formal statistical equivalence was rare (4% valence, 11% arousal, 3% urge), MGAI ratings approximated human ratings closely (Mean difference of mean ratings = - 0.31, SD = 1.23) and correlations between MGAI and human mean ratings were moderate to high: r s (valence) = 0.55, r s (arousal) = 0.34, r s (urge) = 0.56. MGAI also reproduced the parabolic relation between rating means and standard deviations observed in human data. These preliminary results indicate that MGAI can approximate human cannabis cue-reactivity patterns closely enough to justify continued refinement. MGAI could potentially be developed into a Cannabis Regulatory Science tool to aid regulatory oversight of online cannabis marketing.},
}
RevDate: 2025-12-03
Differential regulation of p62-ubiquitin conjugates in neurons versus astrocytes during cellular stress.
bioRxiv : the preprint server for biology pii:2025.11.17.688722.
Sequestosome 1/p62 (hereafter referred to as p62) is a multifunctional protein that orchestrates various cellular stress response pathways including autophagy, proteasome-mediated degradation, antioxidant defense, nutrient sensing, and inflammatory signaling. Mutations in distinct functional domains of p62 are linked with the neurodegenerative disease amyotrophic lateral sclerosis (ALS), underscoring its importance in neural cells. Neurons and astrocytes perform distinct roles in brain physiology and thus encounter a unique landscape of cellular stress. However, how p62 is regulated in these cell types in response to various stress modalities remains largely unexplored. Several functions for p62 depend on engagement with ubiquitinated substrates. Thus, we investigated how the regulation of p62-ubiquitin conjugates differs between neurons and astrocytes exposed to two stress modalities: lysosomal membrane damage and metabolic stress. Lysosomal damage triggered ubiquitin-dependent assembly of p62 puncta in both neurons and astrocytes. In contrast, nutrient deprivation elicited different responses between neurons and astrocytes. Neurons formed p62-ubiquitin structures more prominently and displayed a greater dependence on ubiquitin for p62 clustering. Together, these findings reveal cell-type-specific and stress-specific regulation of p62-ubiquitin conjugates, indicating that neurons and astrocytes can deploy distinct quality control strategies.
Additional Links: PMID-41332782
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@article {pmid41332782,
year = {2025},
author = {Sidibe, DK and Smith, EM and Spivey, ML and Vogel, MC and Maday, S},
title = {Differential regulation of p62-ubiquitin conjugates in neurons versus astrocytes during cellular stress.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.11.17.688722},
pmid = {41332782},
issn = {2692-8205},
abstract = {Sequestosome 1/p62 (hereafter referred to as p62) is a multifunctional protein that orchestrates various cellular stress response pathways including autophagy, proteasome-mediated degradation, antioxidant defense, nutrient sensing, and inflammatory signaling. Mutations in distinct functional domains of p62 are linked with the neurodegenerative disease amyotrophic lateral sclerosis (ALS), underscoring its importance in neural cells. Neurons and astrocytes perform distinct roles in brain physiology and thus encounter a unique landscape of cellular stress. However, how p62 is regulated in these cell types in response to various stress modalities remains largely unexplored. Several functions for p62 depend on engagement with ubiquitinated substrates. Thus, we investigated how the regulation of p62-ubiquitin conjugates differs between neurons and astrocytes exposed to two stress modalities: lysosomal membrane damage and metabolic stress. Lysosomal damage triggered ubiquitin-dependent assembly of p62 puncta in both neurons and astrocytes. In contrast, nutrient deprivation elicited different responses between neurons and astrocytes. Neurons formed p62-ubiquitin structures more prominently and displayed a greater dependence on ubiquitin for p62 clustering. Together, these findings reveal cell-type-specific and stress-specific regulation of p62-ubiquitin conjugates, indicating that neurons and astrocytes can deploy distinct quality control strategies.},
}
RevDate: 2025-12-03
Development of Patient-Derived Neuroprogenitor Cells (hNPCs), Neurons and Astrocytes to Explore the Etiology of Guam Parkinsonism-Dementia Complex (PDC).
bioRxiv : the preprint server for biology pii:2025.10.07.680309.
Parkinsonism-Dementia Complex (PDC) is one phenotype of a disappearing neurodegenerative disease (Guam ALS-PDC) that shows clinical and neuropathological relationships with amyotrophic lateral sclerosis (ALS), atypical parkinsonism and Alzheimer's disease. ALS-PDC has been linked with exposure to environmental factors (notably cycad plant neurotoxins), but evidence from human and animal studies is inconclusive. Patient-derived induced pluripotent stem cells (iPSCs) provide a powerful in vitro system to explore the underlying cause of PDC. iPSC lines were derived from lymphocytes of a PDC-affected Guamanian Chamorro female patient and an age- and gender-matched healthy Chamorro resident of PDC-unaffected Saipan using non-integrating episomal plasmids. iPSCs derived from both patients expressed pluripotency markers (Oct4, SSEA-4, TRA-1-60, Sox2) prior to the generation of neuroprogenitor cells (hNPCs), neurons and astrocytes. An embryoid body protocol was used to derive hNPCs from both iPSC lines while a differentiation media was used to generate neurons from hNPCs. hNPCs derived from both iPSC patients' lines displayed established neuroprogenitor markers (nestin, Sox2), while the differentiated hNPCs exhibited both neuronal (beta-tubulin III, Map2, doublecortin) and synaptic (synaptophysin, PSD-95) markers. Expression of these protein markers in hNPCs and neurons by dot blotting was also observed for both lines. Astrocyte progenitor cells and mature astrocytes with appropriate markers were also developed from the hNPCs of both lines using commercial kits. Development of these patient-derived iPSCs provides a human model for evaluating the role of environmental (e.g., cycad toxins) and genetic factors in ALS-PDC and possibly other related neurodegenerative diseases.
Additional Links: PMID-41332773
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@article {pmid41332773,
year = {2025},
author = {Chlebowski, AC and Yang, Y and Siddique, NA and Siddique, T and Spencer, PS and Steele, JC and Kisby, GE},
title = {Development of Patient-Derived Neuroprogenitor Cells (hNPCs), Neurons and Astrocytes to Explore the Etiology of Guam Parkinsonism-Dementia Complex (PDC).},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.10.07.680309},
pmid = {41332773},
issn = {2692-8205},
abstract = {Parkinsonism-Dementia Complex (PDC) is one phenotype of a disappearing neurodegenerative disease (Guam ALS-PDC) that shows clinical and neuropathological relationships with amyotrophic lateral sclerosis (ALS), atypical parkinsonism and Alzheimer's disease. ALS-PDC has been linked with exposure to environmental factors (notably cycad plant neurotoxins), but evidence from human and animal studies is inconclusive. Patient-derived induced pluripotent stem cells (iPSCs) provide a powerful in vitro system to explore the underlying cause of PDC. iPSC lines were derived from lymphocytes of a PDC-affected Guamanian Chamorro female patient and an age- and gender-matched healthy Chamorro resident of PDC-unaffected Saipan using non-integrating episomal plasmids. iPSCs derived from both patients expressed pluripotency markers (Oct4, SSEA-4, TRA-1-60, Sox2) prior to the generation of neuroprogenitor cells (hNPCs), neurons and astrocytes. An embryoid body protocol was used to derive hNPCs from both iPSC lines while a differentiation media was used to generate neurons from hNPCs. hNPCs derived from both iPSC patients' lines displayed established neuroprogenitor markers (nestin, Sox2), while the differentiated hNPCs exhibited both neuronal (beta-tubulin III, Map2, doublecortin) and synaptic (synaptophysin, PSD-95) markers. Expression of these protein markers in hNPCs and neurons by dot blotting was also observed for both lines. Astrocyte progenitor cells and mature astrocytes with appropriate markers were also developed from the hNPCs of both lines using commercial kits. Development of these patient-derived iPSCs provides a human model for evaluating the role of environmental (e.g., cycad toxins) and genetic factors in ALS-PDC and possibly other related neurodegenerative diseases.},
}
RevDate: 2025-12-03
CmpDate: 2025-12-03
Sensitivity to TDP-43 loss and degradation resistance determine cryptic exon biomarker potential.
bioRxiv : the preprint server for biology pii:2025.11.23.689722.
Cryptic splicing caused by TDP-43 proteinopathy is a hallmark of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, which cryptic splicing events (CEs) are the most sensitive to TDP-43 depletion, where CEs localise within cells, and how specific CEs are in human tissues is poorly defined. Analyses of in vitro TDP-43 knockdowns and postmortem RNA-seq datasets revealed that a small subset out of thousands of CEs are specific markers for TDP-43 proteinopathy in vivo . Nonsense-mediated decay (NMD) masked a portion of CEs, influencing their subcellular localization and detectability in tissue. Dose-dependent TDP-43 depletion identified "early-responsive" CEs, which possess stronger splice sites and denser, more canonical TDP-43 binding motifs. Finally, we developed a composite cryptic burden score that effectively captured TDP-43 pathology across heterogeneous tissues and correlated with regional vulnerability and genetic background. Our work identifies robust biomarkers and offers new insights into TDP-43-mediated splicing dysregulation in neurodegeneration.
Additional Links: PMID-41332610
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@article {pmid41332610,
year = {2025},
author = {Brown, AL and Zanovello, M and Mikheenko, A and Dattilo, D and Pellegrini, F and Bryce-Smith, S and Mattedi, F and Mehta, PR and Vargas, JNS and , and Humphrey, J and Keuss, MJ and Fratta, P},
title = {Sensitivity to TDP-43 loss and degradation resistance determine cryptic exon biomarker potential.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.11.23.689722},
pmid = {41332610},
issn = {2692-8205},
abstract = {Cryptic splicing caused by TDP-43 proteinopathy is a hallmark of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, which cryptic splicing events (CEs) are the most sensitive to TDP-43 depletion, where CEs localise within cells, and how specific CEs are in human tissues is poorly defined. Analyses of in vitro TDP-43 knockdowns and postmortem RNA-seq datasets revealed that a small subset out of thousands of CEs are specific markers for TDP-43 proteinopathy in vivo . Nonsense-mediated decay (NMD) masked a portion of CEs, influencing their subcellular localization and detectability in tissue. Dose-dependent TDP-43 depletion identified "early-responsive" CEs, which possess stronger splice sites and denser, more canonical TDP-43 binding motifs. Finally, we developed a composite cryptic burden score that effectively captured TDP-43 pathology across heterogeneous tissues and correlated with regional vulnerability and genetic background. Our work identifies robust biomarkers and offers new insights into TDP-43-mediated splicing dysregulation in neurodegeneration.},
}
RevDate: 2025-12-03
Spatial Multi-Omics Workflow and Analytical Guidelines for Alzheimer's Neuropathology.
bioRxiv : the preprint server for biology pii:2025.11.16.688710.
Spatial biology technologies enable high-dimensional profiling within intact tissues, revealing how molecular and cellular organization drives function and disease. As these platforms gain broader adoption, standardized analytical frameworks are needed to ensure data quality and reproducibility. Here, we present an end-to-end pipeline for the GeoMx Digital Spatial Profiler that simultaneously generates whole-transcriptome and 637-protein measurements from user-defined regions within the same tissue sections. The workflow integrates morphology-guided region selection, quality control, normalization, and multi-modal data interpretation. Applied to formalin-fixed cortical tissues from Alzheimer's disease, dementia with Lewy bodies, amyotrophic lateral sclerosis, and controls, the framework resolves spatially distinct molecular domains. Transcript and protein signals diverge across amyloid plaque cores and surrounding glial-rich regions, with RNA-protein concordance varying by disease condition, while single-neuron profiling with and without pathogenic tau deposition illustrates protein assay sensitivity. This dataset provides a rigorously validated resource for spatial multi-omic analyses and establishes broadly applicable guidelines for reliable, reproducible profiling of complex tissues.
Additional Links: PMID-41332529
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@article {pmid41332529,
year = {2025},
author = {Sun, X and Hudson, HR and Orr, TC and Koutarapu, S and Rosenbloom, A and Ingalls, M and Braubach, O and Keene, CD and Beechem, JM and Orr, ME},
title = {Spatial Multi-Omics Workflow and Analytical Guidelines for Alzheimer's Neuropathology.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.11.16.688710},
pmid = {41332529},
issn = {2692-8205},
abstract = {Spatial biology technologies enable high-dimensional profiling within intact tissues, revealing how molecular and cellular organization drives function and disease. As these platforms gain broader adoption, standardized analytical frameworks are needed to ensure data quality and reproducibility. Here, we present an end-to-end pipeline for the GeoMx Digital Spatial Profiler that simultaneously generates whole-transcriptome and 637-protein measurements from user-defined regions within the same tissue sections. The workflow integrates morphology-guided region selection, quality control, normalization, and multi-modal data interpretation. Applied to formalin-fixed cortical tissues from Alzheimer's disease, dementia with Lewy bodies, amyotrophic lateral sclerosis, and controls, the framework resolves spatially distinct molecular domains. Transcript and protein signals diverge across amyloid plaque cores and surrounding glial-rich regions, with RNA-protein concordance varying by disease condition, while single-neuron profiling with and without pathogenic tau deposition illustrates protein assay sensitivity. This dataset provides a rigorously validated resource for spatial multi-omic analyses and establishes broadly applicable guidelines for reliable, reproducible profiling of complex tissues.},
}
RevDate: 2025-12-03
Human TDP-43 overexpression in zebrafish motor neurons triggers MND-like phenotypes through gain-of-function mechanism.
Acta neuropathologica communications pii:10.1186/s40478-025-02159-w [Epub ahead of print].
Additional Links: PMID-41331940
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@article {pmid41331940,
year = {2025},
author = {Hogan, AL and Kane, M and Chiu, P and Richter, G and Maurel, C and Wu, S and Scherer, NM and Don, EK and Lee, A and Blair, IP and Chung, RS and Morsch, M},
title = {Human TDP-43 overexpression in zebrafish motor neurons triggers MND-like phenotypes through gain-of-function mechanism.},
journal = {Acta neuropathologica communications},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40478-025-02159-w},
pmid = {41331940},
issn = {2051-5960},
support = {Ideas Grant 2029547//National Health and Medical Research Council/ ; Ideas Grant 2029547//National Health and Medical Research Council/ ; Ideas Grant 2029547//National Health and Medical Research Council/ ; 20200003//The ALS Foundation, Netherlands/ ; DIS-202403-01218//FightMND/ ; },
}
RevDate: 2025-12-02
CmpDate: 2025-12-02
Information technology perception and value cocreation behavior influence patient satisfaction in chronic disease care.
Scientific reports, 15(1):42985.
Patient satisfaction with medical care is one of the key outcome indicators of chronic disease healthcare service quality. However, the factors influencing patient satisfaction, particularly from the perspectives of information technology perception and value cocreation, are underexplored. This study aims to examine the relationships between information technology perception, value cocreation behavior, patient trust, and patient satisfaction in chronic disease patients in China community health centers (CHCs). It also investigates the mediating role of value cocreation behavior and the moderating effect of patient trust. A cross-sectional survey was conducted from September 2019 to December 2019 in Wuhan and Taiyuan, China. Participants were selected using a multistage stratified random sampling method. Data were collected via self-administered questionnaires from 722 chronic disease patients in Wuhan and Taiyuan (with a response rate of 90.36%). Patient satisfaction with medical care was measured using a four-item scale. Information technology perception was assessed using scales for perceived ease of use and perceived reliability, adapted from Deng Chaohua et al.'s measurement of mobile banking system perception. Value co-creation behavior was measured using a 21-item scale adapted from Yi and Gong's measurement of customer value co-creation behavior, and patient trust was measured using a four-item scale. Pearson correlation analysis was used to assess the relationships among perceived ease of use, perceived reliability, value co-creation behavior, patient trust, and patient satisfaction. Structural equation modeling (SEM) was employed to examine the hypothesized relationships among these variables. The proposed model demonstrated good model fit. Perceived ease of use (β = 0.339, 95% CI 0.188 to 0.493) and value cocreation behavior (β = 0.459, 95% CI 0.387 to 0.530) had direct positive effects on patient satisfaction, while perceived reliability (β = 0.049, 95% CI -0.099 to 0.200) did not have a direct effect on patient satisfaction. Perceived ease of use (β=-0.746, 95% CI -0.907 to -0.623) had a direct negative effect on value cocreation behavior, whereas perceived reliability (β = 0.408, 95% CI 0.283 to 0.577) had a direct positive effect on value cocreation behavior. Perceived ease of use (β=-0.342, 95% CI -0.444 to -0.270) and perceived reliability (β = 0.187, 95% CI 0.127 to 0.277) indirectly influenced patient satisfaction through value cocreation behavior. Patient trust had a significant moderating effect on the relationship between value cocreation behavior and patient satisfaction (β = -0.127, 95% CI -0.197 to -0.056). The study reveals that perceived ease of use and value cocreation behavior significantly influence patient satisfaction, with patient trust playing a moderating role in these relationships. These findings suggest that enhancing patients' perception of ease of use and promoting value cocreation behavior can improve patient satisfaction, particularly in contexts with low patient trust. To this end, healthcare providers should optimize the design of information systems to support seamless doctor-patient interactions and encourage active patient participation in care processes. Additionally, policymakers are advised to implement strategies that foster trust and facilitate communication within CHCs, especially for patients with chronic diseases.
Additional Links: PMID-41330986
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@article {pmid41330986,
year = {2025},
author = {Liu, J and Jiang, K and Yang, T and Xu, R and Xuan, Y and Han, Y and Lu, W},
title = {Information technology perception and value cocreation behavior influence patient satisfaction in chronic disease care.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {42985},
pmid = {41330986},
issn = {2045-2322},
support = {72204153//National Natural Science Foundation of China/ ; 72204069//National Natural Science Foundation of China/ ; 821RC578//Project of Hainan Natural Science Foundation/ ; },
mesh = {Humans ; *Patient Satisfaction/statistics & numerical data ; Male ; Female ; Middle Aged ; Chronic Disease/therapy ; Cross-Sectional Studies ; Surveys and Questionnaires ; Adult ; Aged ; China ; Trust ; *Information Technology ; Perception ; },
abstract = {Patient satisfaction with medical care is one of the key outcome indicators of chronic disease healthcare service quality. However, the factors influencing patient satisfaction, particularly from the perspectives of information technology perception and value cocreation, are underexplored. This study aims to examine the relationships between information technology perception, value cocreation behavior, patient trust, and patient satisfaction in chronic disease patients in China community health centers (CHCs). It also investigates the mediating role of value cocreation behavior and the moderating effect of patient trust. A cross-sectional survey was conducted from September 2019 to December 2019 in Wuhan and Taiyuan, China. Participants were selected using a multistage stratified random sampling method. Data were collected via self-administered questionnaires from 722 chronic disease patients in Wuhan and Taiyuan (with a response rate of 90.36%). Patient satisfaction with medical care was measured using a four-item scale. Information technology perception was assessed using scales for perceived ease of use and perceived reliability, adapted from Deng Chaohua et al.'s measurement of mobile banking system perception. Value co-creation behavior was measured using a 21-item scale adapted from Yi and Gong's measurement of customer value co-creation behavior, and patient trust was measured using a four-item scale. Pearson correlation analysis was used to assess the relationships among perceived ease of use, perceived reliability, value co-creation behavior, patient trust, and patient satisfaction. Structural equation modeling (SEM) was employed to examine the hypothesized relationships among these variables. The proposed model demonstrated good model fit. Perceived ease of use (β = 0.339, 95% CI 0.188 to 0.493) and value cocreation behavior (β = 0.459, 95% CI 0.387 to 0.530) had direct positive effects on patient satisfaction, while perceived reliability (β = 0.049, 95% CI -0.099 to 0.200) did not have a direct effect on patient satisfaction. Perceived ease of use (β=-0.746, 95% CI -0.907 to -0.623) had a direct negative effect on value cocreation behavior, whereas perceived reliability (β = 0.408, 95% CI 0.283 to 0.577) had a direct positive effect on value cocreation behavior. Perceived ease of use (β=-0.342, 95% CI -0.444 to -0.270) and perceived reliability (β = 0.187, 95% CI 0.127 to 0.277) indirectly influenced patient satisfaction through value cocreation behavior. Patient trust had a significant moderating effect on the relationship between value cocreation behavior and patient satisfaction (β = -0.127, 95% CI -0.197 to -0.056). The study reveals that perceived ease of use and value cocreation behavior significantly influence patient satisfaction, with patient trust playing a moderating role in these relationships. These findings suggest that enhancing patients' perception of ease of use and promoting value cocreation behavior can improve patient satisfaction, particularly in contexts with low patient trust. To this end, healthcare providers should optimize the design of information systems to support seamless doctor-patient interactions and encourage active patient participation in care processes. Additionally, policymakers are advised to implement strategies that foster trust and facilitate communication within CHCs, especially for patients with chronic diseases.},
}
MeSH Terms:
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Humans
*Patient Satisfaction/statistics & numerical data
Male
Female
Middle Aged
Chronic Disease/therapy
Cross-Sectional Studies
Surveys and Questionnaires
Adult
Aged
China
Trust
*Information Technology
Perception
RevDate: 2025-12-02
Non-cell autonomous autophagy in amyotrophic lateral sclerosis: A new promising target?.
Neurobiology of disease pii:S0969-9961(25)00420-6 [Epub ahead of print].
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative non-cell-autonomous disease with no cure, thus research is intensely focused on identifying pharmacological targets. Several studies aimed to clarify the pathogenic mechanisms and involvement in various cell types. A crucial factor in ALS is autophagy, which plays a key role in degrading intracellular protein aggregates. The connection between ALS and autophagy is reinforced by the fact that several genes mutated in ALS are linked to fundamental aspects of autophagy. The blockage of the autophagic flux was observed in ALS motor neurons, where it occurs earlier than in glia. However, the inconsistent effects of autophagy modulators in preclinical and clinical studies indicate the need for a deeper understanding of the role of autophagy in other cell types, such as astrocytes, microglia, and oligodendrocytes. Astrocytes and microglia are significantly impacted by autophagy dysregulation, contributing to neurodegeneration in both mouse and human-derived models. Autophagy is overactivated early in the disease, even before symptoms appear. This overactivation is influenced by the timing and specific tissue involved. It can alter cells' immunophenotype, favouring proinflammatory responses and affecting the cellular environment and autophagy in the surrounding cells. In contrast, oligodendrocytes show mild autophagic alterations. Additionally, sex hormones may affect proper autophagy function and ALS progression. The lack of information on how sex influences autophagy in glia highlights the need for more nuanced investigation into this mechanism. Future research should focus on these aspects, paving the way for personalised pharmacological approaches that consider the roles of cell types, time of intervention, and sex.
Additional Links: PMID-41330444
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@article {pmid41330444,
year = {2025},
author = {Rosso, F and Magdalena, R and Torazza, C and Bacchetti, F and Milanese, M and Poletti, A and Bonanno, G and Cristofani, R and Bonifacino, T},
title = {Non-cell autonomous autophagy in amyotrophic lateral sclerosis: A new promising target?.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107203},
doi = {10.1016/j.nbd.2025.107203},
pmid = {41330444},
issn = {1095-953X},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative non-cell-autonomous disease with no cure, thus research is intensely focused on identifying pharmacological targets. Several studies aimed to clarify the pathogenic mechanisms and involvement in various cell types. A crucial factor in ALS is autophagy, which plays a key role in degrading intracellular protein aggregates. The connection between ALS and autophagy is reinforced by the fact that several genes mutated in ALS are linked to fundamental aspects of autophagy. The blockage of the autophagic flux was observed in ALS motor neurons, where it occurs earlier than in glia. However, the inconsistent effects of autophagy modulators in preclinical and clinical studies indicate the need for a deeper understanding of the role of autophagy in other cell types, such as astrocytes, microglia, and oligodendrocytes. Astrocytes and microglia are significantly impacted by autophagy dysregulation, contributing to neurodegeneration in both mouse and human-derived models. Autophagy is overactivated early in the disease, even before symptoms appear. This overactivation is influenced by the timing and specific tissue involved. It can alter cells' immunophenotype, favouring proinflammatory responses and affecting the cellular environment and autophagy in the surrounding cells. In contrast, oligodendrocytes show mild autophagic alterations. Additionally, sex hormones may affect proper autophagy function and ALS progression. The lack of information on how sex influences autophagy in glia highlights the need for more nuanced investigation into this mechanism. Future research should focus on these aspects, paving the way for personalised pharmacological approaches that consider the roles of cell types, time of intervention, and sex.},
}
RevDate: 2025-12-02
Trends in Prehospital First-Attempt Use of Supraglottic Airways in Non-Cardiac Arrest Patients: A Descriptive Study.
Prehospital emergency care [Epub ahead of print].
OBJECTIVES: This study aims to characterize the national prehospital trends in primary supraglottic airway use in non-cardiac arrest patients with various methods, including rapid sequence airway (RSA), defined as administration of a sedative and paralytic to facilitate supraglottic airway (SGA) placement. We compared this SGA-first practice to other methods of prehospital airway management.
METHODS: This was a retrospective analysis of a national emergency medical services (EMS) database containing 9-1-1 calls over a five-year period. Only ALS-level calls were included. We compared the incidence of SGA- and tracheal-intubation-first attempts by paramedics. We excluded interfacility transfers, patients in or near cardiac arrest, and surgical airways before intubation.
RESULTS: There were 355,511 encounters with endotracheal tube (ETT) or SGA placement, of which 316,392 patients were excluded, most commonly for cardiac arrest and peri-cardiac arrest, leaving 36,058 (92%) managed with tracheal intubation first and 3,061 (8%) managed with a SGA first. Trauma was the primary reason for encounter for approximately 28% of both groups. SGA-first approaches increased over the five-year period from 3.5% to 8.7% of invasive airway attempts. The type of SGA changed substantially over the study period, with use of the iGel increasing (42% to 82%), and the King LTSD decreasing (50% to 14%). Neuromuscular blocking agents were used in 74% of encounters.
CONCLUSIONS: Among prehospital patients not in cardiac arrest, supraglottic airway devices comprise 8% of initial advanced airway management, with increasing use over time. Placement is usually facilitated by use of a sedative and neuromuscular blocking agent.
Additional Links: PMID-41329328
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@article {pmid41329328,
year = {2025},
author = {Robinson, AE and Knack, SK and Driver, BE and Prekker, ME and Perlmutter, MC and Bunting, AJ and Simpson, NS and Braude, DA and Crowe, RP and Puskarich, MA},
title = {Trends in Prehospital First-Attempt Use of Supraglottic Airways in Non-Cardiac Arrest Patients: A Descriptive Study.},
journal = {Prehospital emergency care},
volume = {},
number = {},
pages = {1-11},
doi = {10.1080/10903127.2025.2593579},
pmid = {41329328},
issn = {1545-0066},
abstract = {OBJECTIVES: This study aims to characterize the national prehospital trends in primary supraglottic airway use in non-cardiac arrest patients with various methods, including rapid sequence airway (RSA), defined as administration of a sedative and paralytic to facilitate supraglottic airway (SGA) placement. We compared this SGA-first practice to other methods of prehospital airway management.
METHODS: This was a retrospective analysis of a national emergency medical services (EMS) database containing 9-1-1 calls over a five-year period. Only ALS-level calls were included. We compared the incidence of SGA- and tracheal-intubation-first attempts by paramedics. We excluded interfacility transfers, patients in or near cardiac arrest, and surgical airways before intubation.
RESULTS: There were 355,511 encounters with endotracheal tube (ETT) or SGA placement, of which 316,392 patients were excluded, most commonly for cardiac arrest and peri-cardiac arrest, leaving 36,058 (92%) managed with tracheal intubation first and 3,061 (8%) managed with a SGA first. Trauma was the primary reason for encounter for approximately 28% of both groups. SGA-first approaches increased over the five-year period from 3.5% to 8.7% of invasive airway attempts. The type of SGA changed substantially over the study period, with use of the iGel increasing (42% to 82%), and the King LTSD decreasing (50% to 14%). Neuromuscular blocking agents were used in 74% of encounters.
CONCLUSIONS: Among prehospital patients not in cardiac arrest, supraglottic airway devices comprise 8% of initial advanced airway management, with increasing use over time. Placement is usually facilitated by use of a sedative and neuromuscular blocking agent.},
}
RevDate: 2025-12-02
Synaptic Vesicle Exocytosis and Endocytosis in Motor Nerve Endings of Transgenic Mice Modeling Amyotrophic Lateral Sclerosis upon Antioxidant Treatment and Gene-Cell Therapy.
Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections [Epub ahead of print].
Exocytosis and endocytosis of synaptic vesicles were studied in experiments with motor nerve endings of diaphragm neuromuscular preparations isolated from transgenic mice with a model of amyotrophic lateral sclerosis (ALS); treatment simulated antioxidant (edaravone) and gene-cell (umbilical cord blood mononuclear cells (UCB-MNCs) producing VEGF, GDNF, and NCAM) therapies. None of the treatments was found to significantly change the FM 1-43 fluorescent dye loading due to synaptic vesicle endocytosis. Gene-cell therapy increased the rate of dye unloading due to synaptic vesicle exocytosis, while antioxidant therapy did not change the FM 1-43 unloading rate. Based on the findings, gene-cell therapy was assumed to facilitate synaptic vesicle transport to release sites upon high-frequency stimulation in motor nerve endings of transgenic mice.
Additional Links: PMID-41329282
PubMed:
Citation:
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@article {pmid41329282,
year = {2025},
author = {Grigoryev, PN and Zefirov, AL and Mukhamedzyanov, RD and Salafutdinov, II and Islamov, RR and Mukhamedyarov, MA},
title = {Synaptic Vesicle Exocytosis and Endocytosis in Motor Nerve Endings of Transgenic Mice Modeling Amyotrophic Lateral Sclerosis upon Antioxidant Treatment and Gene-Cell Therapy.},
journal = {Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections},
volume = {},
number = {},
pages = {},
pmid = {41329282},
issn = {1608-3105},
abstract = {Exocytosis and endocytosis of synaptic vesicles were studied in experiments with motor nerve endings of diaphragm neuromuscular preparations isolated from transgenic mice with a model of amyotrophic lateral sclerosis (ALS); treatment simulated antioxidant (edaravone) and gene-cell (umbilical cord blood mononuclear cells (UCB-MNCs) producing VEGF, GDNF, and NCAM) therapies. None of the treatments was found to significantly change the FM 1-43 fluorescent dye loading due to synaptic vesicle endocytosis. Gene-cell therapy increased the rate of dye unloading due to synaptic vesicle exocytosis, while antioxidant therapy did not change the FM 1-43 unloading rate. Based on the findings, gene-cell therapy was assumed to facilitate synaptic vesicle transport to release sites upon high-frequency stimulation in motor nerve endings of transgenic mice.},
}
RevDate: 2025-12-02
CmpDate: 2025-12-02
Regulatory Functions of TDP-43 and FMRP in Non-Neuronal Diseases: Are Co-Targeted mRNAs the Keys?.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 39(23):e71292.
RNA binding proteins (RBPs) act as the central nodal point in shaping the cellular transcriptome through their involvement in various aspects of RNA metabolism including stability, splicing, polyadenylation, modifications, translation and transport. Dysregulation in the function of various RBPs can be associated with different human pathophysiological conditions. Owing to their ability to regulate various RNA metabolism-associated processes, the same RBPs can functionally be involved in human pathologies with distinct underlying pathophysiological mechanisms. Two such important RBPs, namely TDP-43 and FMRP, have long been implicated respectively, in neurodegenerative diseases like amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) etc. and in neurodevelopmental diseases like fragile-X syndrome (FXS). However, numerous recent reports indicate that these ubiquitously expressed proteins can regulate important cellular functions and signaling cascades, misregulation which results in different disease phenotypes. In this review, the association of TDP-43 and FMRP with different non-neuronal disease mechanisms has been discussed. Furthermore, to anticipate yet-to-be-explored non-neuronal disease mechanisms involving mismanagement in co-regulation of spatial and temporal transport/translation processes of TDP-43 and FMRP targeted RNAs, as observed in neuronal diseases for example, autism, RNA target databases of these two proteins are compared followed by GO and KEGG analysis. The lists of RNAs co-targeted by TDP-43 and FMRP are presumably involved in different non-neuronal diseases and disease-associated mechanistic pathways and will open up new phases of research to establish new disease mechanism(s). Different disease mechanisms and their interconnections expectantly will also lead to the discovery of new drug targets.
Additional Links: PMID-41328916
Publisher:
PubMed:
Citation:
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@article {pmid41328916,
year = {2025},
author = {Ahsan, A and Kar, O and Akter, K and Ta, HDK and Shen, CJ and Datta, K and Chatterjee, B and Huang, CC and Majumder, P},
title = {Regulatory Functions of TDP-43 and FMRP in Non-Neuronal Diseases: Are Co-Targeted mRNAs the Keys?.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {39},
number = {23},
pages = {e71292},
doi = {10.1096/fj.202502281R},
pmid = {41328916},
issn = {1530-6860},
support = {110-2320-B-038-090-MY3//National Science and Technology Council (NSTC)/ ; },
mesh = {Humans ; *Fragile X Mental Retardation Protein/metabolism/genetics ; *DNA-Binding Proteins/metabolism/genetics ; *RNA, Messenger/genetics/metabolism ; Animals ; *Neurodegenerative Diseases/metabolism/genetics ; Amyotrophic Lateral Sclerosis/genetics/metabolism ; Fragile X Syndrome/genetics/metabolism ; },
abstract = {RNA binding proteins (RBPs) act as the central nodal point in shaping the cellular transcriptome through their involvement in various aspects of RNA metabolism including stability, splicing, polyadenylation, modifications, translation and transport. Dysregulation in the function of various RBPs can be associated with different human pathophysiological conditions. Owing to their ability to regulate various RNA metabolism-associated processes, the same RBPs can functionally be involved in human pathologies with distinct underlying pathophysiological mechanisms. Two such important RBPs, namely TDP-43 and FMRP, have long been implicated respectively, in neurodegenerative diseases like amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) etc. and in neurodevelopmental diseases like fragile-X syndrome (FXS). However, numerous recent reports indicate that these ubiquitously expressed proteins can regulate important cellular functions and signaling cascades, misregulation which results in different disease phenotypes. In this review, the association of TDP-43 and FMRP with different non-neuronal disease mechanisms has been discussed. Furthermore, to anticipate yet-to-be-explored non-neuronal disease mechanisms involving mismanagement in co-regulation of spatial and temporal transport/translation processes of TDP-43 and FMRP targeted RNAs, as observed in neuronal diseases for example, autism, RNA target databases of these two proteins are compared followed by GO and KEGG analysis. The lists of RNAs co-targeted by TDP-43 and FMRP are presumably involved in different non-neuronal diseases and disease-associated mechanistic pathways and will open up new phases of research to establish new disease mechanism(s). Different disease mechanisms and their interconnections expectantly will also lead to the discovery of new drug targets.},
}
MeSH Terms:
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Humans
*Fragile X Mental Retardation Protein/metabolism/genetics
*DNA-Binding Proteins/metabolism/genetics
*RNA, Messenger/genetics/metabolism
Animals
*Neurodegenerative Diseases/metabolism/genetics
Amyotrophic Lateral Sclerosis/genetics/metabolism
Fragile X Syndrome/genetics/metabolism
RevDate: 2025-12-02
Agreement Between the Harmonized and the Self-Explanatory Versions of the Revised ALS Functional Rating Scale in a Clinical Setting.
Muscle & nerve [Epub ahead of print].
INTRODUCTION/AIMS: The harmonized version of the ALS Functional Rating Scale - Revised (ALSFRS-R) is typically administered according to standard operating procedures (SOPs) to ensure procedural consistency. In contrast, obtaining the self-explanatory (SE) version of the ALSFRS-R does not include the use of SOPs. The aim of this study was to examine the level of agreement between the harmonized and the SE version of the ALSFRS-R in a cohort of ALS patients.
METHODS: In a prospective study, the harmonized ALSFRS-R was assessed in 107 ALS patients. In parallel, all patients independently completed the ALSFRS-R-SE, either on a printed form (n = 36) or remotely via the ALS App (n = 71). Agreement between methods was investigated using Spearman's correlation, Lin's concordance correlation coefficient (CCC), Deming regression, Bland-Altman plots and item-level statistics including Kendall's tau-b and the Stuart-Maxwell test.
RESULTS: Total scores from ALSFRS-R and ALSFRS-R-SE showed high correlation (ρ = 0.91-0.95) and concordance (CCC > 0.9). Deming regression (intercept≈0; slope≈1) and Bland-Altman analysis (95% of values within limits of agreement [LoA]) revealed no systematic bias. Item-level agreement was high (76.6% on average), with some variability in items such as handwriting, walking, and dyspnea. ALS progression rates were consistent (differences ≤ 0.02). ALSFRS-R-SE remained robust across remote digital and paper-based assessments.
DISCUSSION: The strong agreement between the harmonized and self-explanatory versions of the ALSFRS-R supports their interchangeable use. The SE format may facilitate remote digital assessment and reduce complexity of ALSFRS-R assessment in research and clinical practice. Further studies are warranted to validate the ALSFRS-R-SE across larger cohorts, multiple languages, and diverse rater groups.
Additional Links: PMID-41328555
Publisher:
PubMed:
Citation:
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@article {pmid41328555,
year = {2025},
author = {Maier, A and Koc, Y and Steinfurth, L and Kettemann, D and Norden, J and Riitano, A and Schmitt, P and Kolzarek, F and Subramanian, S and Münch, C and Spittel, S and Meyer, T},
title = {Agreement Between the Harmonized and the Self-Explanatory Versions of the Revised ALS Functional Rating Scale in a Clinical Setting.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70092},
pmid = {41328555},
issn = {1097-4598},
support = {//Boris Canessa ALS Stiftung/ ; H4017703513237604//Martin Herrenknecht Fonds for ALS Research/ ; },
abstract = {INTRODUCTION/AIMS: The harmonized version of the ALS Functional Rating Scale - Revised (ALSFRS-R) is typically administered according to standard operating procedures (SOPs) to ensure procedural consistency. In contrast, obtaining the self-explanatory (SE) version of the ALSFRS-R does not include the use of SOPs. The aim of this study was to examine the level of agreement between the harmonized and the SE version of the ALSFRS-R in a cohort of ALS patients.
METHODS: In a prospective study, the harmonized ALSFRS-R was assessed in 107 ALS patients. In parallel, all patients independently completed the ALSFRS-R-SE, either on a printed form (n = 36) or remotely via the ALS App (n = 71). Agreement between methods was investigated using Spearman's correlation, Lin's concordance correlation coefficient (CCC), Deming regression, Bland-Altman plots and item-level statistics including Kendall's tau-b and the Stuart-Maxwell test.
RESULTS: Total scores from ALSFRS-R and ALSFRS-R-SE showed high correlation (ρ = 0.91-0.95) and concordance (CCC > 0.9). Deming regression (intercept≈0; slope≈1) and Bland-Altman analysis (95% of values within limits of agreement [LoA]) revealed no systematic bias. Item-level agreement was high (76.6% on average), with some variability in items such as handwriting, walking, and dyspnea. ALS progression rates were consistent (differences ≤ 0.02). ALSFRS-R-SE remained robust across remote digital and paper-based assessments.
DISCUSSION: The strong agreement between the harmonized and self-explanatory versions of the ALSFRS-R supports their interchangeable use. The SE format may facilitate remote digital assessment and reduce complexity of ALSFRS-R assessment in research and clinical practice. Further studies are warranted to validate the ALSFRS-R-SE across larger cohorts, multiple languages, and diverse rater groups.},
}
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Robbins holds BS, MS, and PhD degrees in the life sciences. He served as a tenured faculty member in the Zoology and Biological Science departments at Michigan State University. He is currently exploring the intersection between genomics, microbial ecology, and biodiversity — an area that promises to transform our understanding of the biosphere.
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Amyotrophic Lateral Sclerosis, or ALS, is a rare, incurable neuro-degenerative disease, of unknown etiology. With this disease, both upper (brain) and lower (spinal cord) motor neurons progressively degenerate and die, rendering immobile the muscles that they innervated. For anyone with a need or desire to appreciate what is known about ALS, this book provides a good foundation. R. Robbins
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