@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.},
}

@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.},
}

@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.},
}

Humans
*Attention
*Color Perception
*Pattern Recognition, Visual
Female
Male
Young Adult
Adult
Reaction Time

@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.},
}

@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.},
}

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

@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.},
}

@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},
}

@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).},
}

*Amyotrophic Lateral Sclerosis/diagnosis/epidemiology/pathology
Humans
Canada/epidemiology
Longitudinal Studies
Prospective Studies
Biological Specimen Banks
Female
Male
Biomarkers

@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.},
}

@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.},
}

@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},
}

@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.},
}

@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.},
}

@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.},
}

@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.},
}

@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.},
}

@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.},
}

@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.},
}

@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.},
}

*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

@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%.},
}

*Amyotrophic Lateral Sclerosis/diagnosis/physiopathology
Humans
*Speech

@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.},
}

Humans
*Amyotrophic Lateral Sclerosis/physiopathology
*Neck Muscles/physiopathology
Electromyography
Male
Middle Aged
*Muscle Weakness/physiopathology
Female

@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.},
}

Humans
*Tongue/physiology
Male
Pilot Projects
Adult
*User-Computer Interface
Middle Aged
Amyotrophic Lateral Sclerosis/physiopathology/rehabilitation
Spinal Cord Injuries/physiopathology/rehabilitation
Female

@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.},
}

*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

@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.},
}

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

@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.},
}

*Amyotrophic Lateral Sclerosis/physiopathology
Humans
*Brain-Computer Interfaces
Algorithms
*Communication Devices for People with Disabilities
Electroencephalography
Event-Related Potentials, P300
Language

@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).},
}

Humans
*Brain-Computer Interfaces
*Neurofeedback/methods
*Evoked Potentials, Visual/physiology
Male
Adult
Electroencephalography
Female

@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.},
}

*Robotics/instrumentation
Humans
*Self-Help Devices
Equipment Design

@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.},
}

@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.},
}

@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.},
}

@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.},
}

@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.},
}

@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.},
}

@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.},
}

@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.},
}

@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.},
}

@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/ ; },
}

@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.},
}

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

@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.},
}

@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.},
}

@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.},
}

@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.},
}

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

@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.},
}

@article {pmid41328354,
year = {2026},
author = {Huang, Q and Wang, S and Liu, Z and Rao, L and Cheng, K and Mao, X},
title = {Engineering exosomes for targeted neurodegenerative therapy: innovations in biogenesis, drug loading, and clinical translation.},
journal = {Theranostics},
volume = {16},
number = {1},
pages = {545-579},
pmid = {41328354},
issn = {1838-7640},
mesh = {Humans ; *Exosomes/metabolism ; *Neurodegenerative Diseases/drug therapy/therapy ; Animals ; *Drug Delivery Systems/methods ; Blood-Brain Barrier/metabolism ; Bioengineering/methods ; Translational Research, Biomedical ; },
abstract = {Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD) and multiple sclerosis (MS), are characterized by progressive neuronal dysfunction and limited therapeutic options, largely due to the restrictive nature of the blood-brain barrier (BBB). Exosomes, naturally occurring extracellular vesicles (EVs), have gained attention as innovative drug delivery vehicles owing to their intrinsic ability to cross the BBB, minimal immunogenicity, high biocompatibility, and capability to carry diverse therapeutic cargos such as proteins, nucleic acids, and small molecules. Furthermore, exosomes can be bioengineered to enhance drug-loading efficiency and targeting specificity, positioning them as a versatile and effective platform for treating NDDs. In this review, we summarize recent advances in exosome biogenesis, secretion, and engineering, with an emphasis on innovative strategies for exosome isolation, drug loading, and surface modification. We further explore their roles in modulating neuroinflammation, promoting neural regeneration, and enabling precise therapeutic delivery. Critical challenges associated with large-scale production, quality control, and regulatory compliance under Good Manufacturing Practices (GMP) are also discussed. Collectively, these developments underscore the transformative potential of engineered exosomes in advancing precision therapies for neurodegenerative disorders and offer strategic insights into their clinical translation.},
}

Humans
*Exosomes/metabolism
*Neurodegenerative Diseases/drug therapy/therapy
Animals
*Drug Delivery Systems/methods
Blood-Brain Barrier/metabolism
Bioengineering/methods
Translational Research, Biomedical

@article {pmid41327964,
year = {2025},
author = {He, QF and Lin, YH and Zheng, ZL and Zeng, MH and Lin, X and Liu, XY and Kang-Yang, and Zhang, QI and Lin, MT and Wang, N and Wang, ZQ and Lin, F},
title = {Comprehensive Profiling of Annexins in Neuromuscular Disorders Reveals a Unique Signature in Dysferlinopathy.},
journal = {European journal of neurology},
volume = {32},
number = {12},
pages = {e70442},
doi = {10.1111/ene.70442},
pmid = {41327964},
issn = {1468-1331},
support = {2023J01620//Natural Science Fundation of Fujian Province/ ; 2024Y9196//Joint Funds for the Innovation of Science and Technology, Fujian Province/ ; },
mesh = {Humans ; *Muscular Dystrophies, Limb-Girdle/metabolism/pathology ; Male ; *Annexins/metabolism ; Female ; Adult ; Middle Aged ; Muscle, Skeletal/pathology/metabolism ; *Neuromuscular Diseases/metabolism/pathology ; Aged ; Young Adult ; Dysferlin ; },
abstract = {BACKGROUND: Annexins are a family of calcium-dependent membrane-binding proteins implicated in membrane repair and inflammation, yet their immunoreactivity patterns in neuromuscular disorders remain poorly characterized. This study systematically examined the immunoreactivity profiles of annexins A1, A2, A4, A5, A6, A7, and A11 across various muscular dystrophies, including muscular dystrophies, inflammatory myopathies, lipid storage myopathy (LSM), and amyotrophic lateral sclerosis (ALS).

METHODS: Muscle biopsies from patients with dysferlinopathy, Duchenne/Becker muscular dystrophy (DMD/BMD), myotonic dystrophy type 1 (DM1), oculopharyngeal muscular dystrophy (OPMD), facioscapulohumeral muscular dystrophy (FSHD), LSM, inflammatory myopathies, and ALS, along with controls, were analyzed. Immunofluorescence and immunoblot assays were used to assess annexin localization and abundance, and quantitative immunoreactivity levels were statistically compared with controls.

RESULTS: Dysferlinopathy showed a distinct upregulation of multiple annexins (A1, A2, A4, A5, A6, and A7). These annexins were primarily localized to the extracellular matrix, with additional cytoplasmic accumulation in atrophied fibers. Annexin A6 was strongly associated with the sarcolemma, while annexin A7 was diffusely distributed. In contrast, other myopathies such as OPMD and FSHD exhibited reduced or unchanged annexin immunoreactivity. Inflammatory myopathies partially mirrored the dysferlinopathy pattern, though annexin A2 levels were lower. ALS samples displayed minimal immunoreactivity, restricted to focal cytoplasmic annexin A1 and sparse sarcolemmal annexin A6.

CONCLUSIONS: These findings reveal a unique annexin signature in dysferlinopathy, suggesting a potential involvement in membrane repair and inflammatory modulation. The differential expression across disorders highlights the diverse roles of annexins in muscle pathophysiology and supports their utility as diagnostic biomarkers and therapeutic targets.},
}

Humans
*Muscular Dystrophies, Limb-Girdle/metabolism/pathology
Male
*Annexins/metabolism
Female
Adult
Middle Aged
Muscle, Skeletal/pathology/metabolism
*Neuromuscular Diseases/metabolism/pathology
Aged
Young Adult
Dysferlin

@article {pmid41327675,
year = {2025},
author = {Kiristioglu, MO and Akova, B and Sogutlu Sari, E and Baykara, M},
title = {Anterior segment optical coherence tomography in corneal diseases: A bibliometric analysis and visualization research of global research trends (1994-2024).},
journal = {Medicine},
volume = {104},
number = {48},
pages = {e45679},
doi = {10.1097/MD.0000000000045679},
pmid = {41327675},
issn = {1536-5964},
mesh = {*Tomography, Optical Coherence/methods/trends ; *Bibliometrics ; Humans ; *Corneal Diseases/diagnostic imaging ; *Biomedical Research/trends ; *Anterior Eye Segment/diagnostic imaging ; },
abstract = {PURPOSE: This study provides a bibliometric analysis of global research on anterior segment optical coherence tomography (AS-OCT) in corneal diseases, mapping key research trajectories, collaborations, and emerging trends.

METHODS: A systematic search in the Web of Science Core Collection on January 1, 2025, retrieved 3634 records (1994-2024). After excluding non-English publications, non-ophthalmology studies, and non-corneal research, 2079 publications were analyzed using VOSviewer and CiteSpace for citation networks, coauthorship trends, and keyword co-occurrence.

RESULTS: AS-OCT research has grown significantly (Mann-Kendall τ = 0.929, P < .001). The United States led in publications (639 papers, 19,594 citations), followed by China (333 papers, 4502 citations). The University of California was the most productive institution. The first AS-OCT study, published in the Archives of Ophthalmology (1994) by Izatt JA et al, marked the field's inception. The most cited article was Huang et al's 1991 Science paper on optical coherence tomography. Recent trends highlight the integration of artificial intelligence, deep learning, and optical coherence elastography in AS-OCT applications. The top 3 contributing journals were Cornea, Journal of Refractive Surgery, and Journal of Cataract and Refractive Surgery. Coauthorship analysis identified Jodhbir S. Mehta and David Huang as central figures in AS-OCT research collaborations.

CONCLUSION: AS-OCT research has expanded significantly, enhancing diagnostics, surgical planning, and disease monitoring. Artificial intelligence-driven analytics and optical coherence elastography are promising future directions. This bibliometric analysis guides advancing AS-OCT research and clinical applications.},
}

*Tomography, Optical Coherence/methods/trends
*Bibliometrics
Humans
*Corneal Diseases/diagnostic imaging
*Biomedical Research/trends
*Anterior Eye Segment/diagnostic imaging

@article {pmid41327179,
year = {2025},
author = {Eshak, D and Arumugam, M},
title = {Nanomaterials: an overview of current trends and future prospects in neurological disorder treatment.},
journal = {Journal of translational medicine},
volume = {23},
number = {1},
pages = {1366},
pmid = {41327179},
issn = {1479-5876},
mesh = {Humans ; *Nervous System Diseases/therapy/drug therapy ; *Nanostructures/therapeutic use/chemistry ; Animals ; Blood-Brain Barrier ; },
abstract = {The World Health Organization (WHO) has identified neurological disorders (NDs) as one of the major health concerns worldwide, resulting in high mortality rates. NDs are conditions affecting the central and peripheral nervous systems, including the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, neuromuscular junctions, and muscles. These neurological diseases include Alzheimer's disease, Parkinson's disease, glioma/brain cancer, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, neuroinfections, ischemic stroke, trauma, hypoxia/anoxia, and depression. Unfortunately, these disorders remain difficult to treat due to the limited ability of conventional drugs to cross the blood-brain barrier (BBB) and achieve significant pharmacological effects in the brain. There is an urgent need to develop methods that can enhance drug efficacy and bypass the BBB. The application of various nanomaterials represents a promising approach to address these neurological disorders. Drugs incorporated with nanomaterials help improve therapeutic outcomes, reduce toxicity, provide better stability, enable targeted delivery, and enhance drug loading capacity. Numerous types and morphologies of inorganic and organic nanomaterials are increasingly employed for treating NDs, including quantum dots, dendrimers, metal nanoparticles, polymeric nanoparticles, liposomes, carbon nanotubes, metal oxide nanoparticles, and micelles. Their exceptional properties such as sensitivity, selectivity, and potential to bypass the BBB make them suitable for both diagnosis and treatment of NDs. In this review article, we briefly summarize the etiology and pathophysiology of various NDs along with current literature highlighting the use of nanomaterials for treating neurological disorders.},
}

Humans
*Nervous System Diseases/therapy/drug therapy
*Nanostructures/therapeutic use/chemistry
Animals
Blood-Brain Barrier

@article {pmid41326746,
year = {2025},
author = {Stærmose, TS and Blicher, JU and Dalal, SS},
title = {Movement Related Beta-Band Modulation with OPM-MEG: A Pilot Study.},
journal = {Brain topography},
volume = {39},
number = {1},
pages = {3},
pmid = {41326746},
issn = {1573-6792},
mesh = {Humans ; *Magnetoencephalography/methods/instrumentation ; Pilot Projects ; *Amyotrophic Lateral Sclerosis/physiopathology ; Male ; *Beta Rhythm/physiology ; Movement/physiology ; Middle Aged ; Female ; Adult ; Aged ; *Brain/physiopathology/physiology ; },
abstract = {Optically pumped magnetometers (OPMs) represent a significant advancement in magnetoencephalography (MEG), offering high sensitivity without cryogenic cooling and enabling flexible sensor placement. In this pilot study, we evaluated whether a small, zero-contact 16-channel OPM array can capture movement-related beta-band modulation (event-related desynchronization/synchronization; ERD/ERS) in healthy participants and explored feasibility in a single patient with amyotrophic lateral sclerosis (ALS). MEG responses to visually cued active and passive finger movements were recorded in a magnetically shielded room with the OPM array and separately with 306-channel superconducting quantum interference device (SQUID). Time-frequency analyses focused on beta-band activity across baseline, ERD, and ERS periods. In healthy participants, both OPM and SQUID successfully captured movement-related beta oscillations, with no significant differences between active and passive conditions or between measurement systems, based on non-parametric tests. In the ALS patient, movement-related responses were attenuated and more affected by artifacts in the OPM data compared with SQUID, limiting interpretability. Although movement artifacts were noted, the OPM system provided group-level results in healthy controls comparable to SQUID-based MEG, demonstrating its viability and potential for rapid, flexible deployment. These findings indicate that a compact zero-contact OPM array can reliably measure movement-related cortical beta activity and may offer a cost-effective alternative to cryogenic MEG systems. In ALS, however, the present results should be interpreted strictly as a feasibility demonstration, and larger patient cohorts will be required to establish reliability and clinical utility.},
}

Humans
*Magnetoencephalography/methods/instrumentation
Pilot Projects
*Amyotrophic Lateral Sclerosis/physiopathology
Male
*Beta Rhythm/physiology
Movement/physiology
Middle Aged
Female
Adult
Aged
*Brain/physiopathology/physiology

@article {pmid41326138,
year = {2026},
author = {Beggan, A and McGannon, KR},
title = {Reflections on non-WEIRD behavior change and the next generation of physical activity research: A commentary on Simpson et al. (2025).},
journal = {Psychology of sport and exercise},
volume = {82},
number = {},
pages = {102993},
doi = {10.1016/j.psychsport.2025.102993},
pmid = {41326138},
issn = {1878-5476},
mesh = {Humans ; *Exercise/psychology ; *Health Behavior ; *Health Promotion ; },
abstract = {This commentary responds to Simpson et al.'s (2025) call to broaden health behavior change (BC) research in physical activity (PA) beyond WEIRD (Western, Educated, Industrialised, Rich, Democratic) paradigms. Drawing from narrative, discursive, and postqualitative traditions, we reflect on the conceptual and historical meanings of "WEIRD" and explore its limitations. We propose three transgressive directions for future BC and PA research: humility, reflexivity, and attention to wyrd ways of life. These reflections invite researchers to move beyond the 'same old' assumptions and consider culturally situated, relational, and decolonizing approaches that rethink both our conceptions of BC and PA and what our research of them can mean, do, and become.},
}

Humans
*Exercise/psychology
*Health Behavior
*Health Promotion

@article {pmid41323938,
year = {2025},
author = {Kincaid, TK and Christensen, W and Adams, JE and Lockspeiser, T and Kiger, M},
title = {Psychometric Analysis of an Adapted Patient Care Ownership Scale for Medical Students.},
journal = {Perspectives on medical education},
volume = {14},
number = {1},
pages = {860-870},
pmid = {41323938},
issn = {2212-277X},
mesh = {Humans ; *Students, Medical/psychology/statistics & numerical data ; *Psychometrics/methods/instrumentation/standards ; Factor Analysis, Statistical ; *Patient Care/standards/methods/psychology ; Surveys and Questionnaires ; Male ; Female ; *Ownership/statistics & numerical data/standards ; Reproducibility of Results ; Education, Medical, Undergraduate/methods/standards ; Adult ; Colorado ; },
abstract = {PURPOSE: Patient care ownership (PCO) is a commitment to patient care with important implications for both patients and providers, and understanding PCO among trainees is an emerging area of study. Recently, Djulbegovic et al adapted a psychological ownership scale for graduate medical education (GME). Tailoring this scale for undergraduate medical education (UME) would strengthen the ability to measure and promote PCO among students, while directly linking this growth to the transition to GME.

METHOD: Djulbegovic et al.'s PCO scale was adjusted through content expert input and cognitive interviews. This scale was administered to post-clerkship students at the University of Colorado School of Medicine after academic years 2020-21 and 2021-22. Exploratory factor analysis (EFA) was used to examine the underlying themes of the adapted scale in the 2020-21 sample. Confirmatory factor analysis (CFA) was performed in the 2021-22 sample to evaluate factors elucidated in EFA. Messick's validity framework was used to guide collection of content, response process, and internal structure validity evidence.

RESULTS: The final scale included 16, 7-point Likert-style items. EFA modeling in the first sample suggested either a four-factor structure or a two-factor structure that was a simplification of the four-factor structure. CFA modeling in the second sample supported a four-factor model of PCO in medical students, named Advocacy, Decision-making, Opportunity, and Responsibility.

CONCLUSIONS: This PCO scale demonstrated strong internal structure validity evidence and identified four factors contributing to PCO in medical students. Comparing these to Djulbegovic's work elucidates differences between UME and GME learners' experiences of PCO, chiefly in the opportunity of care ownership.},
}

Humans
*Students, Medical/psychology/statistics & numerical data
*Psychometrics/methods/instrumentation/standards
Factor Analysis, Statistical
*Patient Care/standards/methods/psychology
Surveys and Questionnaires
Male
Female
*Ownership/statistics & numerical data/standards
Reproducibility of Results
Education, Medical, Undergraduate/methods/standards
Adult
Colorado

@article {pmid41323796,
year = {2025},
author = {Kang, M and Lin, WH and Li, Y and Xu, F and Zhou, X and Si, C and Dai, J and He, J and Schacht, I and Gan, Z and Huang, V and Li, LC},
title = {SCAD: A modular platform for efficient delivery of duplex RNA to the CNS and beyond.},
journal = {Molecular therapy. Nucleic acids},
volume = {36},
number = {4},
pages = {102757},
pmid = {41323796},
issn = {2162-2531},
abstract = {Oligonucleotide therapeutics-including antisense oligonucleotides and duplex RNAs such as small interfering RNAs, small activating RNAs, and microRNAs-hold immense potential for treating both genetic and acquired diseases by modulating gene expression in a target-specific manner. However, effective delivery to extrahepatic tissues, particularly the central nervous system, remains a significant challenge. While N-Acetylgalactosamine conjugation has enabled liver-specific delivery of oligonucleotides leading to several approved siRNA drugs for hepatic indications, there remains a significant unmet need for effective treatment options in the CNS space. We have developed the smart chemistry-aided delivery platform that enables duplex RNA delivery by conjugating to an accessory oligonucleotide, which facilitates protein binding and promotes cellular uptake. Through extensive screening, we identified an optimal SCAD architecture that demonstrates enhanced cell-free protein binding and in vitro activity. In rodent models, local administration of SCAD-siRNA conjugates resulted in broad biodistribution throughout the CNS and sustained mRNA knockdown for over 5 months, with a favorable safety profile. The SCAD platform also exhibited efficient delivery to other extrahepatic tissues, including the eye, lung, and joint. The modular design of SCAD can be easily adapted to any duplex RNA, making it a powerful tool for advancing oligonucleotide therapeutics.},
}

@article {pmid41323626,
year = {2025},
author = {Pérez-Fuentes, MDC and Molero Jurado, MDM and Romanos-Rodríguez, A and Barragán Martín, AB and Gómez-Gómez, FJ and Aguado-Campos, J},
title = {Simulation-based training in emotional intelligence and self-esteem: enhancing effectiveness and wellbeing in healthcare.},
journal = {Frontiers in public health},
volume = {13},
number = {},
pages = {1667192},
pmid = {41323626},
issn = {2296-2565},
mesh = {Humans ; *Emotional Intelligence ; *Self Concept ; Female ; Male ; Spain ; Adult ; *Simulation Training/methods ; Middle Aged ; *Health Personnel/education/psychology ; Primary Health Care ; Physicians/psychology ; },
abstract = {INTRODUCTION: The study focuses on the training of health professionals, traditionally based on technical skills and specialized knowledge. However, the importance of integrating emotional intelligence and self-esteem has gained recognition for its impact on the quality of patient care and professional wellbeing. This study examines how targeted interventions in these areas can improve wellbeing and professional effectiveness in primary care settings.

METHOD: A multicenter study was conducted with a pre-experimental design, assessing participants before and after the intervention, with no control group. Participants were 106 physicians and nurses in primary care centers in Andalusia, Spain. The intervention consisted of an Advanced Life Support (ALS) training program implemented in a blended learning format that combined online theoretical instruction with in-person practical sessions. The course integrated theoretical modules, hands-on workshops, and simulation-based exercises aligned with international resuscitation guidelines. The Brief Inventory of Emotional Intelligence and the Rosenberg Self-Esteem Scale were used. Data analysis was performed using nonparametric tests and the Wilcoxon test to assess pre- and post-intervention variations.

RESULTS: Correlations between self-esteem and several dimensions of emotional intelligence showed significant post-intervention increases. The intrapersonal and interpersonal factors of emotional intelligence showed significant improvements in their mean scores. However, no significant changes in stress management, mood, or self-esteem were observed in the total sample.

CONCLUSION: The study highlights the efficacy of incorporating emotional intelligence and self-esteem training in the training of health professionals, demonstrating improvements in stress management and adaptability. The variations in the effects of the intervention suggest the need to adapt future interventions to the specific characteristics of each profession. Integrating these programs into health education could significantly enhance the quality of patient care and the wellbeing of health professionals.},
}

Humans
*Emotional Intelligence
*Self Concept
Female
Male
Spain
Adult
*Simulation Training/methods
Middle Aged
*Health Personnel/education/psychology
Primary Health Care
Physicians/psychology

@article {pmid41323448,
year = {2025},
author = {Tang, H and Jiang, P and Chen, J},
title = {Research Landscapes and Gaps in Neuropsychiatric Assessment for Neurodegenerative Diseases: A Bibliometric Study on Huntington's Disease, Amyotrophic Lateral Sclerosis, and Multiple System Atrophy.},
journal = {Dementia and geriatric cognitive disorders extra},
volume = {15},
number = {1},
pages = {174-191},
pmid = {41323448},
issn = {1664-5464},
abstract = {INTRODUCTION: The aim of the study was to provide a comprehensive overview of the current application of tools used for assessing neuropsychiatric symptoms (NPSs) in patients with Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and multiple system atrophy (MSA) through bibliometric analysis.

METHODS: Publications published between 2014 and 2023 were searched using the Web of Science Core Collection database (WoSCC). Only articles and reviews published in the English language were included. CiteSpace was used to analyze the countries, keyword patterns, and reference co-citations. A detailed full-text analysis was further conducted across all studies to assess the usage of NPS assessment tools.

RESULTS: Our analysis included 530 publications demonstrating consistent annual growth, reflecting rising global interest in NPSs within neurodegenerative and neuroinflammatory diseases. However, these studies reveal research deficiency in current assessment methodologies that demands more attention. Research output remains predominantly concentrated in developed nations with aging populations, particularly the USA, which leads in both publication volume and quality. The primary focus of current research involves evaluating the validity of existing assessment tools, while emerging investigations explore next-generation assessment tools designed to enhance diagnostic precision and enable personalized treatment strategies. Despite these advances, widespread clinical adoption remains limited, and further validation studies are required to establish their reliability across diverse populations and disease stages.

CONCLUSION: This study highlights the growing importance of NPSs in neurodegenerative diseases, particularly in HD, ALS, and MSA. We identify hotspots and deficiencies in the research field of validating NPS assessment tools, integrating NPSs into the diagnostic framework and elucidating neurobiological mechanisms. These findings will contribute to enhanced diagnostic and therapeutic approaches for neurodegenerative diseases.},
}

@article {pmid41322641,
year = {2025},
author = {Carvalho, JHS and Faria, BS and Freitas, RC and Brazaca, LC and Janegitz, BC},
title = {Paper-Based Electrochemical Device Modified with Palladium: Sensor for the Detection of Serotonin and an Immunosensor for the Detection of SOD1.},
journal = {ACS omega},
volume = {10},
number = {46},
pages = {55887-55897},
pmid = {41322641},
issn = {2470-1343},
abstract = {The early and accurate detection of superoxide dismutase 1 (SOD1) and other biomarkers is crucial for the diagnosis and monitoring of neurodegenerative diseases such as amyotrophic lateral sclerosis. This study reports the development of a low-cost paper-based electrochemical sensor for the detection of serotonin (5-HT) and an immunosensor for the detection of SOD1, the potential biomarkers associated with these diseases. The sensor was fabricated using a conductive ink composed of carbon nanotubes and glass varnish onto an office paper substrate, with a palladium electrochemically deposited on the working electrode. To improve the device's stability and water resistance, the paper surface was treated with beeswax, enhancing its hydrophobicity. Cyclic voltammetry was used to observe the electrochemical behavior, with differential pulse voltammetry applied to 5-HT. An analytical calibration curve was generated, with a limit of detection of 0.35 μmol/L for 5-HT, demonstrating a linear range of 7.00-100 μmol/L in PBS. The Pd-modified electrode enabled efficient immobilization of antibodies, facilitating the selective detection of SOD1 via antigen-antibody interactions. Electrochemical impedance spectroscopy was employed for label-free SOD1 quantification, yielding a linear response in the range of 1.0-100 nmol·L[-1] and a limit of detection of 0.72 nmol·L[-1]. The proposed electrochemical immunosensor demonstrates high sensitivity, selectivity, and affordability, making it a promising tool for early stage screening of neurodegenerative disease biomarkers in real-world clinical samples.},
}

@article {pmid41322382,
year = {2026},
author = {Happé, F},
title = {Commentary on Ziermans, Hajdúk, Pinkham, et al.'s "Call to Action on Social Cognition Measures in Clinical Research".},
journal = {Schizophrenia research. Cognition},
volume = {43},
number = {},
pages = {100405},
pmid = {41322382},
issn = {2215-0013},
}

@article {pmid41322353,
year = {2025},
author = {Sanghai, N and Barzegar Behrooz, A and Latifi-Navid, H and Fahanik Babaei, J and Tranmer, GK},
title = {Phosphoproteomics-guided tau biomarker discovery in amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD).},
journal = {Frontiers in neuroscience},
volume = {19},
number = {},
pages = {1714196},
pmid = {41322353},
issn = {1662-4548},
}

@article {pmid41322345,
year = {2025},
author = {Senghor, HVF and Rubio, RD and Marco, C and Salazar-Villacorta, A and Padró-Miquel, A and Beltran, S and Matalonga, L and Márquez, F and Sy, HA and Sy, M and Povedano, M and Diop, AG and Ndiaye, M and Rodríguez Cruz, PM},
title = {SYNE1 Deficiency Manifesting Primarily With Motor Neuron Disease.},
journal = {Neurology. Genetics},
volume = {11},
number = {6},
pages = {e200306},
pmid = {41322345},
issn = {2376-7839},
abstract = {BACKGROUND AND OBJECTIVES: SYNE1 deficiency is an autosomal recessive disorder with a broad phenotypic spectrum, most commonly presenting as adult-onset cerebellar ataxia with or without motor neuron dysfunction. We aimed to expand this spectrum by describing the clinical and genetic findings in 2 unrelated families with early-onset motor neuron disease and virtually no cerebellar signs over time.

METHODS: We performed detailed clinical, neurophysiologic, and genetic studies of 2 unrelated families with juvenile amyotrophic lateral sclerosis (ALS) and biallelic variants in SYNE1.

RESULTS: The phenotypes of both families showed onset of symptoms in childhood or adolescence, with signs of upper and lower motor neuron dysfunction in multiple territories suggestive of juvenile ALS. Patients developed progressive muscle weakness, eventually leading to respiratory distress and bulbar signs. Whole-exome sequencing identified SYNE1 biallelic truncating variants in both families: a homozygous nonsense variant, c.23131C>T (p.Gln7711*), in Family 1, and a novel homozygous splice-site variant, c.17851-1G>A, in Family 2. Notably, mild or no cerebellar manifestations were observed during the follow-up.

DISCUSSION: This report highlights a novel phenotype of SYNE1 deficiency characterized by early-onset motor neuron disease and virtually no cerebellar manifestations, broadening the phenotypic spectrum of this complex neurodegenerative disease. These findings support investigating SYNE1 variants in juvenile ALS and including SYNE1 in motor neuron disease gene panels.},
}

@article {pmid41320876,
year = {2025},
author = {Tang, YB and Zhang, J and Liu, Q},
title = {tRNA-derived small noncoding RNAs: Roles in brain aging and neurodegenerative disorders.},
journal = {Zoological research},
volume = {46},
number = {6},
pages = {1575-1587},
doi = {10.24272/j.issn.2095-8137.2025.349},
pmid = {41320876},
issn = {2095-8137},
mesh = {*Aging/physiology ; *Neurodegenerative Diseases/genetics/metabolism ; Animals ; *Brain/physiology/metabolism ; *RNA, Transfer/metabolism/genetics ; *RNA, Small Untranslated/metabolism/genetics ; Humans ; },
abstract = {Transfer ribonucleic acid-derived small ribonucleic acids (tsRNAs) are an emerging class of regulatory noncoding RNAs produced through the precise cleavage of mature or precursor tRNAs (pre-tRNAs). Once considered degradation byproducts, tsRNAs are now recognized as key modulators of gene expression, epigenetic regulation, and cellular stress responses. In recent years, growing evidence has implicated tsRNAs in the aging process of the brain and in the pathogenesis of age-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). These small RNAs are involved in modulating synaptic function, neuronal survival, and neuroinflammation, and their expression profiles are dynamically altered in response to aging and disease-associated stressors. This review summarizes the biogenesis, classification, and molecular and cellular mechanisms of tsRNAs, with an emphasis on their subcellular locations and associated biological functions. We further explore their roles in brain aging and age-related neurodegenerative diseases and the emerging potential of tsRNAs as biomarkers and therapeutic targets for age-related neurological disorders while highlighting current challenges and future directions in this rapidly advancing field.},
}

*Aging/physiology
*Neurodegenerative Diseases/genetics/metabolism
Animals
*Brain/physiology/metabolism
*RNA, Transfer/metabolism/genetics
*RNA, Small Untranslated/metabolism/genetics
Humans

@article {pmid41319477,
year = {2025},
author = {Benussi, A and Vucic, S},
title = {Emergent technologies and applications of TMS and TMS-EEG in clinical neurophysiology for early and differential diagnosis: IFCN handbook chapter.},
journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology},
volume = {182},
number = {},
pages = {2111459},
doi = {10.1016/j.clinph.2025.2111459},
pmid = {41319477},
issn = {1872-8952},
abstract = {This chapter examines how emerging neurophysiological technologies are transforming the early and differential diagnosis of neurological disorders. While imaging and fluid biomarkers have greatly advanced the field, they remain limited by cost, invasiveness, and their inability to directly capture dynamic brain activity. Neurophysiological techniques, particularly transcranial magnetic stimulation (TMS) and TMS combined with EEG, offer a unique, non-invasive means of probing cortical excitability, connectivity, and plasticity with millisecond precision. Recent technological and analytical breakthroughs are moving these approaches from research laboratories into clinical practice. By detecting subtle network dysfunctions that precede structural degeneration, they open the possibility of identifying disease in its prodromal or even presymptomatic stages, when interventions may be most effective. This chapter outlines the principles of advanced TMS paradigms and TMS-EEG and explores their application across a range of conditions, including amyotrophic lateral sclerosis, dementias, and movement disorders. It also highlights how integrating neurophysiological measures with blood-based biomarkers and computational tools, such as machine learning, can enhance diagnostic accuracy and guide individualized treatment strategies. Together, these innovations establish neurophysiology as a cornerstone of precision neurology, linking mechanistic insights to clinical decision-making and enabling earlier diagnosis, improved patient stratification, and more targeted therapeutic interventions.},
}

@article {pmid41319328,
year = {2025},
author = {Michelutti, M and Huppertz, HJ and Anderl-Straub, S and Volkmann, H and Urso, D and Tafuri, B and Nigro, S and Manganotti, P and Rosenbohm, A and Ludolph, AC and Otto, M and Logroscino, G and Müller, HP and Kassubek, J},
title = {MRI-DTI Biomarkers Along the Continuum of Behavioral Variant Frontotemporal Dementia.},
journal = {European journal of neurology},
volume = {32},
number = {12},
pages = {e70438},
pmid = {41319328},
issn = {1468-1331},
mesh = {Humans ; *Frontotemporal Dementia/pathology/diagnostic imaging ; *Diffusion Tensor Imaging/methods ; Male ; Female ; Middle Aged ; Aged ; *White Matter/pathology/diagnostic imaging ; *Amyotrophic Lateral Sclerosis/pathology/diagnostic imaging ; *Gray Matter/pathology/diagnostic imaging ; Magnetic Resonance Imaging/methods ; *Brain/pathology/diagnostic imaging ; Atrophy/pathology ; Biomarkers ; Longitudinal Studies ; },
abstract = {BACKGROUND: We investigated whether diffusion tensor imaging (DTI) and atlas-based volumetry (ABV) could track specific patterns of brain white matter (WM) microstructure and gray matter (GM) volumes in behavioral variant frontotemporal dementia (bvFTD) and amyotrophic lateral sclerosis with frontotemporal dementia (ALS-FTD).

METHODS: MRI datasets from 65 bvFTD (including 19 with longitudinal MRI), 18ALS-FTD, and 39 controls were analyzed. White matter fractional anisotropy (FA) differences were assessed using unbiased Whole Brain-based Spatial Statistics (WBSS) and a hypothesis-driven complementary approach consisting of Tract-Wise FA Statistics (TFAS) in Tracts of Interest (TOIs) and ABV in Structures of Interest (SOIs). FA maps were correlated with disease severity (FTLD-CDR sum of boxes). A random forest algorithm classified participants employing TOI and SOI data.

RESULTS: At baseline, both bvFTD and ALS-FTD exhibited WM changes in several tracts including the uncinate fasciculi, tracts originating in the corpus callosum, and the inferior and superior longitudinal fasciculi. Atrophy was most pronounced in the frontal lobes and caudate nuclei. Longitudinally, bvFTD demonstrated an antero-posterior spread of WM degeneration, particularly along the corpus callosum and inferior longitudinal fasciculus, with relatively modest cortical atrophy progression. Random forest analysis identified the most discriminative TOIs and SOIs including the uncinate fasciculus and the amygdala.

CONCLUSIONS: Our findings demonstrate a similar pattern of structural and microstructural changes in bvFTD and ALS-FTD, with a specific involvement of the corticospinal tract for ALS-FTD, and support the utility of combined DTI and ABV in tracking disease progression across the FTLD spectrum.},
}

Humans
*Frontotemporal Dementia/pathology/diagnostic imaging
*Diffusion Tensor Imaging/methods
Male
Female
Middle Aged
Aged
*White Matter/pathology/diagnostic imaging
*Amyotrophic Lateral Sclerosis/pathology/diagnostic imaging
*Gray Matter/pathology/diagnostic imaging
Magnetic Resonance Imaging/methods
*Brain/pathology/diagnostic imaging
Atrophy/pathology
Biomarkers
Longitudinal Studies

@article {pmid41316902,
year = {2025},
author = {Jang, GE and Lee, I and Andrews, JA and Cheung, YKK and Redzepagic, M and Mitsumoto, H},
title = {Startle Reflex in Primary Lateral Sclerosis (PLS): A Comparison With Amyotrophic Lateral Sclerosis (ALS).},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70071},
pmid = {41316902},
issn = {1097-4598},
support = {//Spastic Paraplegia Foundation/ ; //ALS Association/ ; //Mitsubishi Tanabe Pharma Corporation/ ; //MDA Wings Over Wall Street/ ; //David Marren and the Family/ ; },
abstract = {INTRODUCTION/AIMS: There is a lack of information about startle reflex (SR) in primary lateral sclerosis (PLS). This study examined the presence and prevalence of SR in PLS and compared findings with amyotrophic lateral sclerosis (ALS).

METHODS: 46 PLS and 54 ALS participants were assessed through structured interviews in this cross-sectional study. Fisher's exact test was used to compare reported SR prevalence. Multivariable linear regression was utilized to study associations between disease group and SR frequency in response to sudden stimuli.

RESULTS: SR differed markedly between the two groups, with a higher prevalence in PLS (93.5%) than ALS (20.4%; p < 0.001). Among ALS patients, SR was present in all upper motor neuron (UMN)-predominant cases, which accounted for 54.5% of the SR-positive ALS group, but only 10.4% of probable/definite ALS cases. In SR-positive patients, response frequency to sudden stimuli exceeded 60% in both ALS and PLS, most often triggered by auditory stimuli. Younger age, shorter disease duration, and PLS diagnosis were associated with more frequent SR.

DISCUSSION: SR is significantly more common in PLS than in ALS. Notably, UMN-predominant ALS, although limited in number, showed a higher prevalence of SR (6 out of 6, 100%), indicating that predominant UMN involvement may be a key determinant of SR across both conditions. These hypothesis-generating findings suggest that SR may serve as a novel clinical marker in PLS and UMN-predominant ALS, warranting further validation through prospective studies.},
}

@article {pmid41316805,
year = {2025},
author = {Taha, M and Huang, S and Wang, X and Subasi, A and Morren, JA},
title = {Electromyography Signal Classification With Artificial Intelligence for Detection of Neuromuscular Disorders Using a Large Clinically-Acquired Database.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70087},
pmid = {41316805},
issn = {1097-4598},
support = {//Cleveland Clinic Foundation/ ; //Lerner Research Institute-Artificial Intelligence in Medicine (AIM) Internal Funding Program/ ; },
abstract = {INTRODUCTION/AIMS: Artificial intelligence (AI) has shown potential in analyzing electromyography (EMG) signals, but clinical applicability remains limited by studies based on small, curated datasets, and variable accuracy. This study evaluated AI performance in classifying needle electromyography (EMG) signals as muscle activity versus background/noise/artifact, and then in distinguishing three clinical categories: amyotrophic lateral sclerosis (ALS), myopathy, and non-disease controls.

METHODS: Data from the Cleveland Clinic Foundation EMG Database (CCFDB), a large clinically acquired EMG dataset was utilized for this study. A two-step classification approach was used: a convolutional neural network (CNN) to separate muscle activity from background/noise/artifact, followed by a random forest algorithm and CNNs for clinical category classification. Feature extraction techniques included Short-Time Fourier Transform (STFT), Discrete Wavelet Transform (DWT), Continuous Wavelet Transform (CWT), and Wavelet Packet Decomposition (WPD).

RESULTS: EMG data from 608 participants (266 ALS, 89 myopathy, 253 non-disease controls), totaling 11,456 muscle recordings, and 15,613 segments of muscle activity were included. The muscle activity detection model achieved 85.4% accuracy. For clinical category classification, CWT with a two-layer CNN performed best on the CCFDB (62% accuracy). Deeper CNN architectures did not consistently improve performance. On the publicly available curated EMGlab dataset, the best accuracy using the same AI models was higher (91%).

DISCUSSION: AI can assist in EMG analysis, but the performance gap between curated and clinically-acquired datasets underscores the need for robust models capable of handling signal variability and complexity in authentic clinical contexts. Future efforts should focus on clinically-oriented AI development to improve translational applicability.},
}

@article {pmid41316718,
year = {2025},
author = {Vasta, R and Matteoni, E and Pellegrino, G and Canosa, A and Manera, U and Palumbo, F and Grassano, M and Cabras, S and Maccabeo, A and D'Ovidio, F and Mora, G and Gallone, S and D'Angelo, E and Mazzini, L and De Marchi, F and Moglia, C and Chiò, A and Calvo, A},
title = {The Epidemiology of Primary Lateral Sclerosis: Results from a Population-Based Cohort.},
journal = {Annals of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ana.78105},
pmid = {41316718},
issn = {1531-8249},
abstract = {OBJECTIVE: In this population-based study, we described the epidemiology of primary lateral sclerosis (PLS) in northern Italy and compared the clinical characteristics of patients with PLS to those with predominant upper motor neuron (PUMN) involvement and classic amyotrophic lateral sclerosis (ALS).

METHODS: Patients from the PARALS registry diagnosed with probable or definite PLS between 2007 and 2021 were included. Crude annual incidence rates were calculated, along with age- and sex-specific rates. A survival analysis was performed to identify prognostic factors at diagnosis. Covariates included sex, age at onset, site of onset, diagnostic delay, forced vital capacity (FVC), change in ALS Functional Rating Scale (ΔFRS), and change in body mass index (ΔBMI).

RESULTS: A total of 57 PLS patients (2.7%) were included, with a crude incidence rate of 0.084 per 100,000 person-years. Compared to PUMN and classic ALS, PLS patients were younger (median onset age 63.5 years, interquartile range [IQR] 54.9-70.4) and predominantly female (male-to-female ratio 0.58). Bulbar onset occurred in 11 cases (19.3%), all of whom later developed spinal symptoms. At censoring, 38 patients (66.7%) were still alive (median survival 8.3 years, IQR 5.7-12.3), corresponding to a point prevalence of 0.89 per 100,000. Survival was significantly associated with age at onset (hazard ratio [HR] 1.17, 95% confidence interval [CI]: 1.05-1.33, p = 0.001), male sex (HR 4.41, 95% CI: 1.24-15.6, p = 0.02), and FVC at diagnosis (HR 0.95, 95% CI: 0.93-0.98, p = 0.006).

INTERPRETATION: PLS was confirmed to be rarer than other ALS phenotypes. Patients had a higher age at onset than previously reported and a female predominance. Sex, age at onset, and respiratory function were key prognostic factors. ANN NEUROL 2025.},
}

@article {pmid41315851,
year = {2025},
author = {Xu, H and Li, B and Chen, Y and Lin, Y and Zhang, A and Wu, L},
title = {N-palmitoyl glycine differentially modulates TRPM4 and TRPC5 and is causally linked to Brugada syndrome.},
journal = {Communications biology},
volume = {},
number = {},
pages = {},
doi = {10.1038/s42003-025-09296-x},
pmid = {41315851},
issn = {2399-3642},
support = {81930105//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82370312//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
abstract = {Brugada syndrome (BrS) is an inherited cardiac arrhythmic disorder associated with an increased risk of malignant ventricular arrhythmia and sudden death. Mendelian randomisation implicated N-palmitoyl glycine (PalGly) in BrS risk and identified BrS-associated proteins (DCC, CR1, CTSB, NAAA, DEFB1, EPHA1, IGF1/IGFBP3/ALS, and LTA), for which molecular docking further predicted moderate binding affinities with PalGly. PalGly enhanced calcium sparks in ventricular cardiomyocytes without affecting Nav1.5 or Kv4.3/KChiP2 but activated TRPC5 (EC50 104 nM), as confirmed by patch-clamp. TRPM4, a channel mediating sodium influx at negative potentials and reported to link to BrS when mutated, was directly inhibited by PalGly (IC50 = 7 nM). Functionally, PalGly shortened APD in cardiomyocytes and QT in male rabbit hearts, whereas ML204 (TRPC5 inhibitor) further shortened APD in isolated cardiomyocytes. Transcriptomic and lipidomic analyses further indicated immune pathway suppression. Our study underscores the involvement of PalGly, TRPC5, and inflammation-related proteins in the pathophysiology of BrS.},
}

@article {pmid41315422,
year = {2025},
author = {Wang, S and Yao, T},
title = {Multi-omics framework integrating genetics microbiome and immunity for understanding motor neuron degeneration pathogenesis.},
journal = {NPJ biofilms and microbiomes},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41522-025-00874-9},
pmid = {41315422},
issn = {2055-5008},
support = {2020B22//Doctoral Fund of The First Affiliated Hospital of Harbin Medical University/ ; 2022-KYYWF-0301//Innovative Scientific Research Funding Project of Harbin Medical University/ ; PL2024H140//Natural Science Foundation of Heilongjiang Province/ ; ZL2024H001//The Key Project of the Joint Fund of the Natural Science Foundation of Heilongjiang Province/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) remains a devastating neurodegenerative disorder with poorly understood pathogenesis. We conducted Mendelian randomization (MR) analyses integrating cardiovascular factors, gut microbiota (GM) composition, and immune cell phenotypes with transcriptomic profiling to establish causal relationships with ALS susceptibility. MR revealed causal associations between elevated low-density lipoprotein cholesterol, apolipoprotein B, systolic blood pressure, and increased ALS risk. GM analysis identified protective Alistipes species effects and detrimental Bacteroides associations. Multiple immune cell subsets demonstrated significant disease associations, particularly CD3 + T cell populations and CD62L+ monocytes. Colocalization studies identified 53 genes with shared genetic architecture, enabling differential expression analysis across datasets. Predictive modeling developed a five-gene biomarker panel achieving 96% training accuracy and 93% external validation. Quantitative PCR confirmed differential expression patterns for biomarkers in patient cohorts. This multi-omics investigation establishes ALS as a complex disorder with actionable cardiovascular and microbiome therapeutic targets, providing applications for risk stratification and prevention.},
}

@article {pmid41315129,
year = {2025},
author = {Vandermorris, A and Metzger, DL and Vyver, E and Harrison, M and Wong, S and , },
title = {Response to Kulatunga Mourzi et al.'s (2025) "The Cass Review and Gender-Related Care for Young People in Canada: A Commentary on the Canadian Paediatric Society Position Statement on Transgender and Gender-Diverse Youth".},
journal = {Archives of sexual behavior},
volume = {},
number = {},
pages = {},
pmid = {41315129},
issn = {1573-2800},
}

@article {pmid41314748,
year = {2025},
author = {Quadri, SN and Tiwari, S and Siddiqi, B and Fatima, S and Khan, MA and Abdin, MZ},
title = {Advanced neuroimaging in precision neurology: Tools, trends, and translational impact.},
journal = {Progress in brain research},
volume = {297},
number = {},
pages = {221-246},
doi = {10.1016/bs.pbr.2025.08.005},
pmid = {41314748},
issn = {1875-7855},
mesh = {Humans ; *Neuroimaging/methods/trends ; *Neurodegenerative Diseases/diagnostic imaging ; *Precision Medicine/methods/trends ; Translational Research, Biomedical ; *Neurology/methods/trends ; Artificial Intelligence ; Machine Learning ; },
abstract = {Advances in neuroimaging are revolutionizing the landscape of precision neurology by enabling high-resolution, multimodal visualization of brain structure, function, and pathology. As traditional, symptom-based frameworks fall short in capturing the biological complexity of neurodegenerative diseases, imaging modalities such as structural MRI, diffusion tensor imaging, functional MRI, PET, and hybrid PET/MRI have emerged as essential tools for early diagnosis, patient stratification, and therapeutic monitoring. These technologies not only reveal hallmark features like hippocampal atrophy and disrupted neural networks but also uncover molecular signatures such as amyloid and tau deposition, synaptic density, and neuroinflammation. Integration with artificial intelligence (AI) and machine learning (ML) further enhances diagnostic precision by decoding subtle imaging patterns, facilitating subtype classification, and predicting disease progression. Despite transformative progress, disparities in access and implementation remain a critical challenge, particularly in low- and middle-income countries. This chapter provides a comprehensive overview of neuroimaging modalities, their diagnostic and prognostic relevance across major neurodegenerative conditions including Alzheimer's disease, Parkinson's disease, ALS, and frontotemporal dementia and the evolving role of hybrid platforms and AI integration in shaping the future of individualized neurological care.},
}

Humans
*Neuroimaging/methods/trends
*Neurodegenerative Diseases/diagnostic imaging
*Precision Medicine/methods/trends
Translational Research, Biomedical
*Neurology/methods/trends
Artificial Intelligence
Machine Learning

@article {pmid41314746,
year = {2025},
author = {Ceballos, MWG and Sy, FFA and Akbar, A and Taofiq, A},
title = {Multi-omics integration in disease research.},
journal = {Progress in brain research},
volume = {297},
number = {},
pages = {155-189},
doi = {10.1016/bs.pbr.2025.08.012},
pmid = {41314746},
issn = {1875-7855},
mesh = {Humans ; *Neurodegenerative Diseases/genetics/metabolism ; *Proteomics/methods ; *Genomics/methods ; *Metabolomics/methods ; Animals ; Multiomics ; },
abstract = {Neurodegenerative diseases, marked by complex molecular mechanisms and diverse clinical features, challenge conventional research approaches. This chapter emphasizes the value of multi-omics integration in understanding the biology of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS). Genomic studies reveal risk variants such as APOE ε4 in Alzheimer's and rare mutations in familial forms. Transcriptomics highlights gene expression changes, including synaptic dysfunction in early Parkinson's and alternative splicing errors in TARDBP-related ALS. Proteomics identifies key protein aggregates like amyloid beta and alpha-synuclein, along with modifications such as hyperphosphorylated tau that correlate with cognitive decline. Metabolomics uncovers metabolic alterations, including mitochondrial dysfunction in Parkinson's and lipid peroxidation in ALS, which contribute to disease progression. By combining these layers with high-throughput tools like single-cell sequencing, spatial transcriptomics, and mass spectrometry, researchers can reconstruct molecular networks linking genetic risk, gene regulation, protein dysfunction, and metabolic imbalance. This approach enables patient stratification into molecular subtypes, such as neuroinflammatory clusters defined by microglial gene signatures and cytokine expression. Biomarkers from blood and cerebrospinal fluid allow for minimally invasive disease monitoring. Despite challenges such as data heterogeneity and limited standardization, multi-omics approaches support biomarker discovery and therapeutic development. Integrating these datasets with neuroimaging and digital tools enhances diagnostic precision and guides targeted interventions, such as antisense therapies for SOD1-linked ALS. Multi-omics integration is thus a critical foundation for advancing personalized strategies in neurodegenerative disease research.},
}

Humans
*Neurodegenerative Diseases/genetics/metabolism
*Proteomics/methods
*Genomics/methods
*Metabolomics/methods
Animals
Multiomics

@article {pmid41314745,
year = {2025},
author = {Fatima, S and Tiwari, S and Siddiqi, B and Quadri, SN and Abdin, MZ},
title = {Biomarkers: From early detection to treatment personalization.},
journal = {Progress in brain research},
volume = {297},
number = {},
pages = {131-153},
doi = {10.1016/bs.pbr.2025.08.008},
pmid = {41314745},
issn = {1875-7855},
mesh = {Humans ; *Biomarkers/metabolism ; *Neurodegenerative Diseases/diagnosis/therapy/metabolism ; *Precision Medicine/methods ; Early Diagnosis ; },
abstract = {Neurodegenerative disorders (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), present increasing issues associated with the unavoidable aging of the world's population. These challenges are further highlighted by the socioeconomic consequences of these diseases. The identification and use of biomarkers for prompt diagnosis, careful observation, and efficient treatment approaches is essential to overcoming these obstacles. The primary methods for diagnosing neurodegenerative illnesses are invasive procedures like lumbar punctures to measure CSF fluid or functional brain imaging methods. Biomarkers for underlying proteinopathy in blood serum and cerebral fluid have been the focus of recent biological research, particularly in vivo. With their ability to provide novel pathways for early detection, illness progression tracking, and individualized treatment plans, biomarkers have become essential instruments in precision medicine. The classification of biomarkers including fluid, digital imaging, and molecular biomarkers is examined in this chapter, with an emphasis on their function in neurodegenerative diseases. In neurodegenerative illnesses and the aging brain, tau, amyloid-β, α-synuclein, and TDP-43 are commonly seen to be deposited together rather than separately. These may be disregarded, and it might be challenging to determine their clinicopathological significance. An overview of illness pathophysiology, diagnostic implications, and the most recent molecular and ultrastructural categories for neurodegenerative disorders are given in this chapter. Addressing these issues through interdisciplinary research and technological advancements will be crucial for the future of biomarker-driven precision medicine. This chapter provides an in-depth overview of the evolving landscape of biomarkers and their transformative impact on the early detection and personalized treatment of neurodegenerative diseases.},
}

Humans
*Biomarkers/metabolism
*Neurodegenerative Diseases/diagnosis/therapy/metabolism
*Precision Medicine/methods
Early Diagnosis

@article {pmid41314744,
year = {2025},
author = {Gunasekaran, B and Arifin, AH and Yu, WH and Hanafi, S and Rao, KDK and Salvamani, S},
title = {Precision medicine in neurodegenerative diseases: From research to clinical practice.},
journal = {Progress in brain research},
volume = {297},
number = {},
pages = {1-52},
doi = {10.1016/bs.pbr.2025.08.006},
pmid = {41314744},
issn = {1875-7855},
mesh = {Humans ; *Precision Medicine/methods ; *Neurodegenerative Diseases/therapy/genetics/diagnosis ; Biomarkers ; },
abstract = {The chapter outlines how precision medicine is reshaping the way neurodegenerative diseases (NDs) which includes Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD) are understood, diagnosed, and treated. It discusses the limitations of current therapies, which mainly address symptoms without altering disease progression. Genetic and molecular factors that influence disease development are described, including distinctions between familial and sporadic forms. The chapter also covers the roles of epigenetic changes, gene expression, protein dysfunction, mitochondrial DNA, and non-coding RNAs in NDs. Biomarkers in blood and cerebrospinal fluid, along with imaging techniques and digital tools, are presented as key elements in early diagnosis and disease monitoring. Patient stratification based on clinical features, molecular profiles, and biomarkers helps guide treatment decisions and improve outcomes. The chapter reviews ongoing developments in genotype-based drug design, gene therapy, pharmacogenomics, and personalized lifestyle strategies. Clinical case studies show how these approaches are being used in practice. The chapter also discusses challenges in applying precision medicine, such as trial design, data integration, unequal access, and regulatory hurdles. Finally, it highlights the future tools like single-cell transcriptomics, digital twins, and global research collaborations that aim to bring precision approaches into everyday care.},
}

Humans
*Precision Medicine/methods
*Neurodegenerative Diseases/therapy/genetics/diagnosis
Biomarkers

@article {pmid41314255,
year = {2025},
author = {Odonchimed, S and Imamura, K and Inoue, H},
title = {Neurodegenerative Disease and Autophagy in iPSC models.},
journal = {Neuroscience research},
volume = {},
number = {},
pages = {104991},
doi = {10.1016/j.neures.2025.104991},
pmid = {41314255},
issn = {1872-8111},
abstract = {Neurodegenerative diseases are characterized by the gradual deterioration of specific neuronal populations, ultimately resulting in motor, cognitive, or behavioral impairments. Despite the worldwide increase in disease incidence, effective therapies remain unavailable. A common pathological hallmark of neurodegenerative diseases is the accumulation of misfolded protein aggregates, which impair normal cellular function. Accordingly, numerous studies and therapeutic strategies have focused on targeting these toxic aggregates and protein quality control via autophagy, a vital cellular recycling mechanism. Autophagy dysregulation has been implicated in the pathogenesis of several neurodegenerative diseases. Induced pluripotent stem cell (iPSC) technology has emerged as a powerful platform for modeling neurodegenerative diseases, and iPSC-derived models provide human-relevant systems for studying autophagic dysfunction in vitro. In this review, we discuss the key findings of recent studies investigating autophagy in iPSC-based models of neurodegenerative diseases, including Alzheimer's disease, amyotrophic lateral sclerosis, frontotemporal dementia, and other diseases.},
}

@article {pmid41314187,
year = {2025},
author = {Taher, Y and Ibrahim, S and Ahmed, D},
title = {BENIGN FASCICULATION SYNDROME AMONG HEALTH CARE WORKERS, A SINGLE CENTER STUDY.},
journal = {Georgian medical news},
volume = {},
number = {366},
pages = {64-68},
pmid = {41314187},
issn = {1512-0112},
mesh = {Humans ; Male ; *Health Personnel/psychology ; Female ; Cross-Sectional Studies ; Middle Aged ; Adult ; *Fasciculation/epidemiology/physiopathology/diagnosis/psychology ; *Anxiety/epidemiology/physiopathology ; *Depression/epidemiology/physiopathology ; Amyotrophic Lateral Sclerosis/physiopathology/epidemiology ; Prevalence ; Syndrome ; Electromyography ; Surveys and Questionnaires ; },
abstract = {BACKGROUND: Benign fasciculation syndrome (BFS) is a neurological disease manifested as persistent muscle twitching with the absence of a serious underlying pathology. Unlike the fasciculations that characterizes the most serious condition like amyotrophic lateral sclerosis (ALS), the BFS is not associated with weakness or muscle atrophy. Although the exact underlying mechanism of BFS is not well understood, it seems that anxiety, depression and the fear from having ALS play an important role especially among health care workers.

AIM: To detect the frequency and characteristics of BFS among a group of health care workers and to verify its possible correlation with the anxiety, depression and fear of having MND.

PATIENTS AND METHOD: In this comparative cross-sectional study, BFS was diagnosed in health care workers as well as the comparative group reflecting general population based on the clinical characteristics of fasciculation and by having normal neurological examination and normal nerve conduction study (NCS) and electromyograph (EMG). Anxiety and depression will be assessed according to generalized anxiety disorder 7 score (GAD-7) and patients health questionnaire 9 (PHQ-9).

RESULT: Our study revealed a significantly higher prevalence of Benign Fasciculation Syndrome (BFS) among healthcare workers (13.9%) compared to the general population (3.0%). This difference was statistically significant (p=0.002), indicating that healthcare workers face over five times the odds of developing BFS. Among affected healthcare workers, the most frequently reported clinical features accompanying fasciculations were perceived motor weakness (33.3%), sensory symptoms (26.7%), and tremor (26.7%). The average duration of symptoms was just over three years. A striking finding was the strong association between BFS and psychological comorbidities. Within the BFS group, 60% of individuals suffered from anxiety, with over half of these cases classified as severe. Similarly, 33.3% of BFS patients were diagnosed with depression. Statistical analysis confirmed that healthcare workers with anxiety or depression had a five-fold increased risk of having BFS compared to their non-affected colleagues (p=0.003 and p=0.016, respectively).

CONCLUSIONS: In conclusion, this study identifies healthcare workers as a population at significantly increased risk for Benign Fasciculation Syndrome (BFS). The condition is strongly associated with and likely precipitated by high rates of severe anxiety and depression within this cohort. These findings underscore the critical importance of integrating psychological screening and mental health support into the diagnostic and therapeutic management of BFS for healthcare professionals.},
}

Humans
Male
*Health Personnel/psychology
Female
Cross-Sectional Studies
Middle Aged
Adult
*Fasciculation/epidemiology/physiopathology/diagnosis/psychology
*Anxiety/epidemiology/physiopathology
*Depression/epidemiology/physiopathology
Amyotrophic Lateral Sclerosis/physiopathology/epidemiology
Prevalence
Syndrome
Electromyography
Surveys and Questionnaires

@article {pmid41313609,
year = {2025},
author = {Maciel, ACMG and da Silva, AAM and Medeiros da Fonseca, JD and Vieira, RGDS and da Silva, LS and Lima, TBWE and Pondofe, KM and Otto-Yáñez, M and Torres-Castro, R and Vera-Uribe, R and Vilaró, J and Dourado Junior, MET and Resqueti, VR and Fregonezi, GAF},
title = {Effects of Body Position on Respiratory Pressure and Muscle Activity in Amyotrophic Lateral Sclerosis and Healthy Subjects.},
journal = {Respiratory care},
volume = {},
number = {},
pages = {},
doi = {10.1177/19433654251389828},
pmid = {41313609},
issn = {1943-3654},
abstract = {Background: Amyotrophic lateral sclerosis (ALS) is a fatal heterogeneous neurodegenerative disease characterized by the degeneration of both upper and lower motor neurons and spinal cord. Measurement of respiratory muscle strength has been shown to be an important assessment in the decision-making process and can be assessed by maximum inspiratory (PImax) and expiratory pressures (PEmax), sniff nasal inspiratory (SNIP) and expiratory (SNEP) pressures. Body position appears to have a significant effect on respiratory muscle strength. The aim of this study was to observe the difference in peak values of SNIP and SNEP of the respiratory muscles measured in 2 different positions (seated and supine with 45° elevation) in subjects with ALS and a group of matched healthy subjects. Methods: This is a case-control study of subjects with ALS and healthy subjects. Spirometry and surface electromyography (EMG) of the sternocleidomastoid, scalene, rectus abdominis, and external oblique muscles were assessed during PImax and PEmax maneuvers in the seated position, and SNIP and SNEP in the seated and supine positions at 45° elevation (randomized). Results: SNEP values in the 45° elevation were lower than in the sitting position in ALS (70.3 ± 26.7 vs 57.3 ± 22.8 cm H2O, P = .041). SNIP and SNEP were lower in ALS in the 45° elevation compared with healthy subjects (69.1 ± 27.2 vs 95.5 ± 23.5 cm H2O; 57.3 ± 22.5 vs 92.7 ± 26.4 cm H2O, P = .041). In subjects with ALS, baseline electromyographic activity of the sternocleidomastoid muscle at rest was higher than in healthy subjects in both positions (P = .041). No significant differences in electrical activity were found for other variables and measurements. Conclusions: In ALS, nasal pressure may be affected by reduced diaphragm and abdominal muscle effectiveness in the supine position. The sternocleidomastoid muscle showed increased electrical activity in the supine position with 45° elevation compared with controls, which may indicate muscle weakness.},
}

@article {pmid41313410,
year = {2025},
author = {Goel, F and Singh, P and Rai, SN and Yadav, DK},
title = {Nrf2/Keap1 Signaling Axis in the Brain: Master Regulator of Oxidative Stress in Neurodegenerative and Psychiatric Disorders.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {197},
pmid = {41313410},
issn = {1559-1182},
mesh = {Humans ; *Kelch-Like ECH-Associated Protein 1/metabolism ; *NF-E2-Related Factor 2/metabolism ; *Signal Transduction/physiology ; *Oxidative Stress/physiology ; *Mental Disorders/metabolism/pathology ; Animals ; *Neurodegenerative Diseases/metabolism/pathology ; *Brain/metabolism/pathology ; },
abstract = {Oxidative stress is a crucial factor in the development of CNS disorders, including neurodegenerative and psychiatric conditions. The Nrf2/Keap1 signaling axis plays a central role in defending against oxidative damage by regulating antioxidant and cytoprotective gene expression. Beyond its antioxidant function, Nrf2 influences neurogenesis, synaptic plasticity, mitochondrial bioenergetics, and glial neuronal interactions, all of which are vital for maintaining neural integrity and cognitive performance. Dysregulation of this pathway through altered dimerization, post-translational modifications, or impaired regulation contributes to the pathophysiology of Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, leading to protein aggregation, mitochondrial dysfunction, and neuroinflammation. Emerging evidence also implicates aberrant Nrf2 activity in psychiatric disorders such as depression, schizophrenia, and bipolar disorder, where redox imbalance and neuroimmune activation disrupt neural function. This review summarizes the molecular structure and regulation of the Nrf2/Keap1 pathway, including basal and stress-induced activation, post-translational modifications, and cross-talk with PI3K/Akt, MAPK, and NF-κB signaling. We highlight cell-type-specific roles of Nrf2 in neurons, astrocytes, and microglia, and the gene expression networks that drive CNS antioxidant and detoxification responses. Recent therapeutic strategies include natural and synthetic Nrf2 activators, gene therapy approaches, and nanotechnology-based delivery systems. While the translational potential of Nrf2-targeted interventions is considerable, challenges remain, including risks of overactivation and oncogenicity, lack of reliable biomarkers, and barriers related to blood-brain barrier permeability, dose, timing, and bioavailability. By integrating advances in neuroscience, pharmacology, and molecular medicine, this review emphasizes the promise of Nrf2 as a unifying therapeutic target across diverse CNS pathologies. Future directions include precision modulation through epigenetic regulation and circRNAs, as well as personalized pharmacotherapy. The Nrf2/Keap1 axis represents a multidisciplinary platform for developing multimodal interventions to preserve brain health in neurodegenerative and psychiatric disorders.},
}

Humans
*Kelch-Like ECH-Associated Protein 1/metabolism
*NF-E2-Related Factor 2/metabolism
*Signal Transduction/physiology
*Oxidative Stress/physiology
*Mental Disorders/metabolism/pathology
Animals
*Neurodegenerative Diseases/metabolism/pathology
*Brain/metabolism/pathology

@article {pmid41312566,
year = {2025},
author = {Kwinta, R and Morawiec, N and Bączyk, J and Kubicka-Bączyk, K and Adamczyk-Sowa, M},
title = {Aging immunity - the role of T and B cells in neurological disorders among older adults.},
journal = {Neurologia i neurochirurgia polska},
volume = {},
number = {},
pages = {},
doi = {10.5603/pjnns.106498},
pmid = {41312566},
issn = {0028-3843},
abstract = {INTRODUCTION: Immunosenescence is a natural process of immune system aging, which leads to significant changes in the functioning of both innate and adaptive immunity. Alterations in T and B lymphocytes can significantly impact the progression of neurological diseases including multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS).

STATE OF THE ART: Immunosenescence affects T and B cell subsets, reducing their proliferative capacity and altering cytokine profiles. In MS, these changes promote disease progression and diminish responses to immunomodulatory therapies. In AD and PD, dysfunctional T and B cells contribute to sustained neuroinflammation, exacerbating neurodegeneration. ALS is similarly associated with altered adaptive immunity.

CLINICAL IMPLICATIONS: Recognizing how immunosenescent T and B cells contribute to disease in older adults is crucial for refining treatment strategies. These age-related immune changes may explain varied responses to therapies and highlight the need for novel approaches targeting the aged immune system in neurodegenerative diseases.

FUTURE DIRECTIONS: Future research should focus on identifying the mechanisms by which immunosenescent lymphocytes modulate neuroinflammation and neurodegeneration in aging populations. Novel biomarkers and immunomodulatory therapies tailored to older adults could significantly improve outcomes in patients with neurological diseases.},
}

@article {pmid41311968,
year = {2025},
author = {Ogura, T and Matsuura, U and Machida, M and Nagai, K and Kajimoto, S and Tahara, S and Nakabayashi, T},
title = {RNA-Mediated Inhibition Mechanism of Liquid-Liquid Phase Separation and Subsequent Aggregation Revealed by Raman Microscopy.},
journal = {JACS Au},
volume = {5},
number = {11},
pages = {5749-5757},
pmid = {41311968},
issn = {2691-3704},
abstract = {Liquid-liquid phase separation (LLPS) is a phenomenon where homogeneous solutions of biomacromolecules separate into two liquid phases and generate liquid droplets enriched in specific biomolecules. LLPS of neurodegeneration-related proteins, including fused in sarcoma (FUS), promotes their aggregation, causing fatal diseases such as amyotrophic lateral sclerosis (ALS). Recent studies showed that RNAs regulate LLPS of these proteins and inhibit their aggregation, which may play an important role in preventing the disease onset; however, the underlying molecular mechanisms remain elusive. It is also unknown whether endogenous RNAs regulate LLPS and subsequent aggregation in cells. In this study, we investigated features of RNAs that enable their entrance into FUS droplets and inhibition of FUS aggregation via droplets and clarified the underlying mechanisms using Raman microscopy. We found that RNA length is one of the primary factors governing both the aggregation-inhibition effect and the localization of RNAs in the droplets in buffer solutions. Short (<50-nt) RNAs were concentrated inside the droplets and inhibited the aggregation. Our quantification method using Raman microscopy revealed that the short RNAs are enriched in FUS droplets by binding to FUS proteins through electrostatic interactions. On the other hand, long (>1000-nt) RNAs were not concentrated and dissolved the droplets. Raman imaging of living cells revealed that intracellular FUS droplets are enriched with endogenous RNAs at levels comparable to in vitro droplets and exhibit high fluidity, confirming that endogenous RNAs play a crucial role in suppressing droplet-to-aggregate transition of FUS in cells. These findings indicate that short RNAs stabilize FUS droplets through heterotypic RNA-FUS interactions that compete with homotypic FUS-FUS direct contacts responsible for aggregation, whereas binding of long RNAs enhances FUS solubility and promotes droplet dissolution. Our study highlights the protective role of RNAs against pathogenic aggregation of neurodegeneration-related proteins via droplets.},
}

@article {pmid41311831,
year = {2025},
author = {Guan, S and Wang, S and Shi, Y and Leng, Y and Ming, Y and Hou, Z and Yu, Y and Wang, Z and Liu, J},
title = {Comparative safety analysis of Riluzole, Edaravone and Tofersen in ALS management: insights from FAERS database.},
journal = {Frontiers in pharmacology},
volume = {16},
number = {},
pages = {1687698},
pmid = {41311831},
issn = {1663-9812},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder. Riluzole, Edaravone, and Tofersen, three promising treatments, have distinct profiles that merit comparative analysis to guide clinical decision-making.

METHODS: This study utilizes a pharmacovigilance analysis of adverse events reported in the FDA Adverse Event Reporting System database from Q1 2004 to Q2 2024. Employing disproportionality, we assessed and compared the AE signals associated with Riluzole, Edaravone, and Tofersen to elucidate their safety profiles in ALS treatment. Finally, applying the Random Walk with Restart (RWR) algorithm to the protein-protein interaction (PPI) network for selecting drug target genes that have a strong correlation genes associated with severe adverse reactions. Finally, their interactions with the target were assessed through molecular docking and transcriptome analysis.

RESULTS: The analysis included 2106 AE reports for Riluzole, 2466 AE reports for Edaravone, and 136 for Tofersen. Highlights the higher incidence of adverse reactions associated with Riluzole, including abdominal discomfort, hypoaesthesia oral, and hepatic enzyme increased, as well as a significant correlation between Edaravone and falls, gait disturbance, and aphasia. Tofersen exhibits different adverse reactions compared to Riluzole and Edaravone, such as headaches, csf red blood cell count positive. Comparative analysis revealed that the three drugs shared a serious adverse reaction, which is thrombosis. RWR analysis identified seven targets related to thrombosis caused by the three drugs, including F10 and MMP9. Subsequently, molecular docking and transcriptome analysis indicate a favorable binding interaction between the drug candidate and the F10 molecule.

CONCLUSION: This comprehensive evaluation underscores the importance of understanding the distinct AE profiles of Riluzole, Edaravone, and Tofersen in clinical practice, providing valuable insights for personalized ALS management. Future research with rigorous prospective designs is recommended to validate these findings and explore the mechanisms underlying the reported adverse events.},
}

@article {pmid41311585,
year = {2025},
author = {Norton, MJ and Byrne, JP and Bedenik, T and Ryan, M and Brogan, C and Dwyer, D and Walsh, K and Ní Shé, É},
title = {Understanding the Mechanisms that Operate within CHIME: A Realist Review Protocol.},
journal = {HRB open research},
volume = {8},
number = {},
pages = {94},
pmid = {41311585},
issn = {2515-4826},
abstract = {BACKGROUND: Recovery originated from the civil rights movement of the 1960s/70s. However, no universally accepted definition of recovery had been constructed until 1993 when William A. Anthony suggested that recovery involved living one's best life even with mental health difficulties. In 2011, Leamy et al. created CHIME [ Connectiveness, Hope, Identity, Meaning and purpose and Empowerment]. A concept that represents the key characteristics of recovery. It derived from a literature review into recovery from psychosis. Since 2011, the literature has examined these concepts individually and collectively to understand what they are in reality. However, few studies have investigated the internal mechanisms that causes a person to move from unwellness to recovery via CHIME. As such this proposed realist review will explore how and why the mechanisms within CHIME operate in individuals recovering from mental health challenges.

METHODS: This review forms work package one of a PhD study into CHIME and mental health recovery in Ireland. It complies with relevant guidelines relating to realist reviews including Pawson et al's. updated methodology, which consists of six phases: 1) setting up the review advisory panel and constructing initial programme theories; 2) searching for evidence; 3) selecting and appraising evidence; 4) extracting data; 5) analysing and synthesising data; and 6) ethics and dissemination.

This proposed review will address a gap in the literature on the mechanism involved in recovery from mental health challenges. Unlike other review types, a realist review is theory orientated, allowing one to answer this review question by exploring how, why, and through what circumstances individuals reach recovery through CHIME. This review will inform future work packages of this PhD study. The proposed review will be written up and submitted to a peer-reviewed journal. Dissemination outside academia will be considered.

REGISTRATION ID: CRD420251038961.},
}

@article {pmid41309196,
year = {2025},
author = {Jamwal, RS and Sharma, B and Minerva, and Gupta, A and Misri, S and Shankaryan, R and Shah, R and Kumar, R},
title = {Protein misfolding and its dual role in neurodegeneration and cancer progression.},
journal = {Advances in protein chemistry and structural biology},
volume = {148},
number = {},
pages = {355-377},
doi = {10.1016/bs.apcsb.2025.10.001},
pmid = {41309196},
issn = {1876-1631},
mesh = {Humans ; *Neoplasms/metabolism/pathology ; *Protein Folding ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; Disease Progression ; Unfolded Protein Response ; },
abstract = {Protein misfolding is a fundamental biological process with profound implications for human health and disease. Typically, proteins assume precise three-dimensional structures to perform their functions, a process safeguarded by the proteostasis network, which comprises molecular chaperones, the ubiquitin-proteasome system (UPS), and autophagy. However, genetic mutations, oxidative stress, and environmental insults can disrupt folding, leading to the accumulation of non-functional or toxic conformations. In neurodegenerative diseases such as Huntington's disease (HD), Parkinson's disease (PD), Alzheimer's disease (AD), Amyotrophic lateral Sclerosis (ALS), chronic misfolding results in toxic protein aggregates like amyloid-β, tau, and α-synuclein. These disrupt synaptic function, induce oxidative and nitrosative stress, and trigger apoptosis, ultimately leading to progressive neuronal loss. Dysregulation of the unfolded protein response (UPR) and weakened proteostasis with aging exacerbate disease pathology. In contrast, cancer cells utilize protein misfolding to enhance their survival and progression. Misfolded oncoproteins, such as mutant p53, not only evade degradation but also acquire oncogenic properties. Tumor cells hijack the UPR and chaperone networks, upregulate heat shock proteins, and manipulate oxidative stress responses to withstand hypoxia, nutrient deprivation, and rapid proliferation. Cancer stem cells (CSCs) further adapt to proteotoxic stress, contributing to tumor heterogeneity, therapy resistance, and immune evasion. The dual role of protein misfolding, driving degeneration in neurons while supporting proliferation in tumors, underscores its centrality in disease biology. Future research should focus on identifying early biomarkers of proteostasis imbalance and exploiting shared molecular pathways for the development of novel therapeutic interventions.},
}

Humans
*Neoplasms/metabolism/pathology
*Protein Folding
*Neurodegenerative Diseases/metabolism/pathology
Animals
Disease Progression
Unfolded Protein Response

@article {pmid41308261,
year = {2025},
author = {Shimano, K and Hattori, T and Yasuda, E and Hase, T and Kina, S and Miyake, T and Yokota, T},
title = {Explainable machine learning algorithm for classifying resting-state functional MRI in amyotrophic lateral sclerosis.},
journal = {Neural networks : the official journal of the International Neural Network Society},
volume = {196},
number = {},
pages = {108359},
doi = {10.1016/j.neunet.2025.108359},
pmid = {41308261},
issn = {1879-2782},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects multiple brain systems. Altered brain function can be observed through resting-state functional magnetic resonance imaging (rs-fMRI). While machine learning offers significant advantages in capturing complex signal patterns across numerous voxels, its decision-making process often lacks transparency. This study aimed to develop an explainable machine learning pipeline to classify patients with ALS and healthy control (HC) using rs-fMRI data.

METHODS: Thirty patients with ALS and 30 HCs were enrolled. The pipeline consisted of three key components: (1) preprocessing of rs-fMRI data using independent component analysis, followed by dual regression to reduce dimensionality and generate individual network maps; (2) training of a three-dimensional convolutional neural network (3D-CNN) to classify each individual image as either ALS or HC; and (3) application of saliency map and Grad-CAM++ to visualize the reasoning behind the model's classification.

RESULTS: The 3D-CNN achieved high classification accuracy using the sensorimotor network (SMN) map (78.3%) and the visual network (VN) map (83.3%). Simultaneously, saliency map and Grad-CAM++ highlighted brain regions that contributed to the classification, and some of which were consistent with regions showing intergroup differences in the dual regression analysis.

DISCUSSION: This study developed a novel explainable machine learning model capable of extracting features and classifying rs-fMRI data. Our results showed altered functional integrity in the SMN and VN in ALS. Our pipeline holds the potential to extract features of rs-fMRI data, enabling classification of neurological diseases with explainability.},
}

@article {pmid41307881,
year = {2025},
author = {Bazo Perez, M and de Carvalho, PHB and Frazier, LD},
title = {Examining the factor structure and measurement invariance of the online-administered Eating Disorder Examination-Questionnaire and the Eating Attitudes Test-26 in young and middle-aged women.},
journal = {Eating and weight disorders : EWD},
volume = {},
number = {},
pages = {},
doi = {10.1007/s40519-025-01802-8},
pmid = {41307881},
issn = {1590-1262},
support = {SEED Funds Award//FIU Psychology Department/ ; Dissertation Fellowship//FIU University Graduate School/ ; General Grant//Mental Research Institute/ ; },
abstract = {PURPOSE: Widely used eating disorder (ED) measures, such as the Eating Disorder Examination-Questionnaire (EDE-Q) or the Eating Attitudes Test-26 (EAT-26), were originally developed and standardized in young White women, leading to poor performance, unclear factor structures, and inconsistent measurement invariance across diverse groups. As ED prevalence rises among middle-aged women, the need for age-appropriate and psychometrically sound assessment tools has become increasingly important. This study evaluated the factor structure, measurement invariance, and internal consistency of the EDE-Q and EAT-26 when administered online across two developmentally relevant age groups: emerging adults and middle-aged women.

METHOD: A sample of 829 women from across the U.S. (emerging adults: 419; middle-aged: 410) completed the EDE-Q and EAT-26 through an online survey platform. We tested the original factor structures and two alternative models for each measure through confirmatory factor analysis. Measurement invariance analyses were conducted on good-fitting models.

RESULTS: The original EDE-Q model failed to converge, while the original EAT-26 model demonstrated poor fit. The alternative factor models-Grilo et al.'s (2013) EDE-Q model, and Bazo Perez et al.'s (2023) EAT-26 model-demonstrated best fit and measurement invariance across both age groups. The EDE-Q subscales exhibited good internal consistency, while the EAT-26 showed acceptable to good internal consistency.

CONCLUSION: These findings emphasize the need for developmentally sensitive tools to improve diagnostic accuracy, early detection, and treatment of EDs across the lifespan. Because the factor structure and measurement invariance results reflect online administration, they should be interpreted within this context and motivate continued evaluation of these instruments across administration formats. Addressing a critical gap in ED research and clinical practice, this work underscores the need to refine ED assessment methods, to ensure equitable, accurate, and developmentally appropriate identification of ED risk in women beyond early adulthood.

LEVEL OF EVIDENCE: V, descriptive (cross-sectional) study.},
}

@article {pmid41307665,
year = {2025},
author = {Montalesi, E and Caissutti, D and Moliterni, C and Ferrante, A and Pepponi, R and Garofalo, T and Sorice, M and Misasi, R and Candelise, N},
title = {Proteostasis network response to environmental chronic stress: linking survival to protein aggregation in a human neuroblastoma cellular model.},
journal = {Cellular and molecular life sciences : CMLS},
volume = {82},
number = {1},
pages = {430},
pmid = {41307665},
issn = {1420-9071},
support = {I83C22002190005//Istituto Superiore di Sanità/ ; AR224190750776B1//Sapienza Università di Roma/ ; B89J22001910007//Fondazione Cassa di Risparmio di Pistoia e Pescia/ ; 2022APEBMY//Ministero dell'Università e della Ricerca/ ; 2022XL4TE9_003//Ministero dell'Università e della Ricerca/ ; P2022LZP9T//Ministero dell'Università e della Ricerca/ ; 20223RXEEC//Ministero dell'Università e della Ricerca/ ; },
mesh = {Humans ; *Neuroblastoma/metabolism/pathology ; *Proteostasis ; Cell Line, Tumor ; *Stress, Physiological ; DNA-Binding Proteins/metabolism ; *Protein Aggregates ; Autophagy ; Cell Survival ; Proteasome Endopeptidase Complex/metabolism ; Phosphorylation ; *Protein Aggregation, Pathological/metabolism ; },
abstract = {Proteins tend to misfold upon stressful events that alter their homeostasis, potentially leading to protein aggregation. A tight regulation of synthesis, folding and degradation, defined as proteostasis network (PN), is required to ensure the functionality of the cell. PN is of utmost importance in post-mitotic cells such as neurons, where protein quality must be preserved for their entire lifetime. Most neurodegenerative disorders are associated with dysregulation of this network. Here, we describe the alteration in key components of the PN during chronic stress and link them with the increase in the amyloid burden and with the aggregation of the protein TDP-43, a major player in Amyotrophic Lateral Sclerosis and other neurodegenerative diseases. Neuroblastoma SH-SY5Y cells were treated with a panel of environmental stressors and analyzed after 24 h and 72 h. Treatments resulted in altered PN functionality, including proteasome impairment, halted protein synthesis, engulfed bulk and selective autophagy, in the absence of overt cell death. Thioflavin staining showed increased amyloid burden throughout treatments, associated with phosphorylated TDP-43 (pTDP-43). Biochemical analyses further revealed the cleavage and increased insolubility of pTDP-43. Our results suggest that TDP-43 is a central player during the integrated stress response to chr onic insults and that increased amyloid burden may reflect the global wellfare of a cellular system, pointing toward the alteration of the PN as the main drive for the onset of sporadic neurodegenerative disorders.},
}

Humans
*Neuroblastoma/metabolism/pathology
*Proteostasis
Cell Line, Tumor
*Stress, Physiological
DNA-Binding Proteins/metabolism
*Protein Aggregates
Autophagy
Cell Survival
Proteasome Endopeptidase Complex/metabolism
Phosphorylation
*Protein Aggregation, Pathological/metabolism

@article {pmid41307543,
year = {2025},
author = {Macpherson, CE and Wani, DK and Li, H and Rana, V and Blacutt, M and Bello-Haas, VD and Quinn, L},
title = {Physical Therapist Interventions for People with Amyotrophic Lateral Sclerosis Across Disease Stages: A Systematic Review of Efficacy.},
journal = {Physical therapy},
volume = {},
number = {},
pages = {},
doi = {10.1093/ptj/pzaf142},
pmid = {41307543},
issn = {1538-6724},
abstract = {IMPORTANCE: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease causing declines in muscular strength that affect respiratory function and functional independence. Although physical therapist interventions have been studied in ALS, their efficacy and evidence quality have not been systematically assessed across disease stages.

OBJECTIVE: The objective of this study was to examine the efficacy of physical therapist interventions on clinical outcomes across ALS disease stages.

DESIGN: This study was a systematic review using Joanna Briggs Institute methodology.

SETTING: Multiple settings were used.

PARTICIPANTS: The participants were adults (>18 years old) with ALS or motor neuron disease.

INTERVENTIONS: Physical therapist interventions within the professional scope of practice included therapeutic exercise, pulmonary training, manual therapy, and multimodal approaches.

OUTCOME MEASURES: Outcome measures included effect sizes (ESs) and 95% CIs calculated for forced vital capacity (FVC) and the Amyotrophic Lateral Sclerosis Rating Scale (ALSFRS) or the ALSFRS revised (ALSFRS-R).

RESULTS: Six databases were searched from inception to January 2025. Thirty-nine studies were included (25 experimental, 14 observational). Outcomes were heterogeneous, with 94 measures across studies: 23 included the ALSFRS or ALSFRS-R, and 16 included FVC. Most interventions targeted early-stage ALS (n = 27), limiting comparisons across stages. Multimodal training had moderate-quality evidence, with moderate effects on the ALSFRS-R (ES = 0.56 [95% CI = 0.09 to 1.03]), and low-quality evidence, with negligible effects on FVC (ES = -0.03 [95% CI = -1.47 to 1.41]). Pulmonary interventions had moderate-quality evidence, with small effects on FVC (ES = 0.40 [95% CI = -0.18 to 0.98]), and low-quality evidence, with negligible effects on the ALSFRS-R (ES = 0.04 [95% CI = -0.25 to 0.33]).

CONCLUSIONS: A range of physical therapist interventions for ALS were assessed, although most were early phase or low quality. Multimodal and pulmonary interventions showed modest benefits in the ALSFRS-R and FVC, respectively. However, variability in outcome measures and limited research beyond early-stage disease highlight the need for stage-specific trials using consistent functional outcomes.

RELEVANCE: This review highlights the breadth of studies of physical therapy in ALS and underscores the need for more rigorous, targeted research.},
}

@article {pmid41307139,
year = {2025},
author = {Al Assaad, H and Messabih, K and Bendjaballah-Lalaoui, N and Boucheffa, Y and Thibault-Starzyk, F and Travert, A},
title = {High-temperature CO2 capture by Li4SiO4: IR spectroscopic evidence for the double shell model.},
journal = {Physical chemistry chemical physics : PCCP},
volume = {},
number = {},
pages = {},
doi = {10.1039/d5cp02957k},
pmid = {41307139},
issn = {1463-9084},
abstract = {This study investigates the mechanisms of CO2 capture by Li4SiO4 employing in situ Fourier transform infrared spectroscopy (FT-IR) combined with multivariate data analysis, with particular attention being paid to the influence of structural modifications derived from natural diatomite on the CO2 sorption performance of Li4SiO4. Three samples were examined: a reference Li4SiO4 material synthesized from pure SiO2 (SiO2-LS), a stoichiometric mixture using calcined diatomite (ND-LS) and an over-stoichiometric sample containing 10% calcined diatomite (10% ND-LS). FTIR analysis confirmed the formation of carbonate species during CO2 uptake. Chemometric analysis using principal component analysis (PCA) and multivariate curve resolution-alternating least squares (MCR-ALS) allowed identification of the successive formation of two distinct carbonate species (species 1 and species 2), supporting the double-shell carbonation model. In ND-derived samples, a distinct band at 1140 cm[-1], attributed to the symmetric stretching vibration (ν1) of a carbonate species associated with magnesium carbonates, was identified. The presence of surface MgCO3 associated with species 1 in ND-derived samples was found to enhance CO2 capture kinetics by facilitating carbonate layer formation through interfacial diffusion pathways. This study provides valuable insights into the carbonation mechanisms of Li4SiO4, demonstrating that calcined diatomite improves CO2 uptake efficiency and opening new perspectives for the optimization of lithium silicate-based CO2 sorbents through targeted compositional modifications.},
}

@article {pmid41306922,
year = {2025},
author = {Bhuiyan, TR and Khanam, F and Basher, SR and Dash, P and Chowdhury, MI and Haque, S and Harun, NB and Akter, A and Karmakar, PC and Hakim, A and Amin, S and Kamruzzaman, M and Parvin, N and Ahmed, T and Butts, J and Pasetti, MF and Wahid, R and Sztein, MB and Maier, N and White, JA and Tomashek, KM and Bourgeois, AL and Baqar, S and Kotloff, KL and Qadri, F and Chen, WH},
title = {Safety and immunogenicity of a recombinant double-mutant heat-labile toxin derived from enterotoxigenic Escherichia coli in healthy Bangladeshi adults delivered by three different routes.},
journal = {Frontiers in bacteriology},
volume = {4},
number = {},
pages = {},
pmid = {41306922},
issn = {2813-6144},
support = {HHSN272200800013C/AI/NIAID NIH HHS/United States ; HHSN272200800057C/AI/NIAID NIH HHS/United States ; INV-008763/GATES/Gates Foundation/United States ; },
abstract = {INTRODUCTION: Enterotoxigenic Escherichia coli (ETEC) is a common cause of acute watery diarrhea in areas lacking access to clean water, sanitation, and hygiene. This Phase 1 trial measured the safety and immunogenicity of double-mutant heat-labile enterotoxin (dmLT) of ETEC in healthy adults in Bangladesh, where ETEC is endemic.

METHODS: Five cohorts of 15 participants each were enrolled and randomized 4:1 to receive vaccine dmLT or placebo (12 vaccine and 3 placebo recipients per cohort). The 3 oral or sublingual doses of 5 μg or 25 μg dmLT were administered 2 weeks apart; the 2 intradermal doses of 0.3 μg dmLT were administered 3 weeks apart. Safety was assessed by collecting solicited and unsolicited adverse events. The immune responses measured included dmLT-specific serum IgA and IgG, serum toxin neutralizing antibody, dmLT-specific IgA and IgG antibody secreting cells (ASC), and IgA and IgG antibodies in lymphocyte supernatant (ALS).

RESULTS: All doses of dmLT delivered by different routes were well tolerated; adverse events were few, mild, and transient. Serum, ALS, and ASC IgA and IgG responses, as well as LT neutralizing antibody responses, were greatest among recipients of 25 μg oral and 0.3 μg intradermal doses. In contrast, sublingual dosing induced modest responses; there was virtually no serum antibody response to 5 μg sublingual dose and only sporadic ALS and ASC responses with 5 μg and 25 μg doses.

DISCUSSION: In conclusion, dmLT was well tolerated, and immune responses were dependent on dmLT dose and route of administration. The encouraging tolerability and immunogenicity results further highlight dmLT's potential not only as a vaccine but also as an adjuvant as reported by others or as a candidate vaccine antigen.

CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov, identifier NCT03548064.},
}

@article {pmid41306819,
year = {2025},
author = {Hsueh, SJ and Hsueh, HW and Chen, YF and Chen, TF and Tsai, LK and Chiang, MC and Hsieh, ST and Wu, WC and Chao, CC},
title = {Implications of perivascular spaces in amyotrophic lateral sclerosis: clinical significance and structural correlation.},
journal = {Brain communications},
volume = {7},
number = {6},
pages = {fcaf448},
pmid = {41306819},
issn = {2632-1297},
abstract = {Perivascular space (PVS) dysfunction may potentially contribute to the development and progression of amyotrophic lateral sclerosis (ALS). This study investigated the clinical relevance of PVS dysfunction in ALS. Two PVS parameters were quantified in patients with ALS: (i) the enlarged perivascular space (ePVS) score and (ii) the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index. These parameters were analysed in relation to the clinical, structural and prognostic features of ALS. The study included 55 patients with ALS (33 men; mean age, 61.38 ± 10.95 years). The DTI-ALPS index was markedly reduced in the patients compared to age- and gender-matched controls, and there were no differences in ePVS scores between the two groups. The ePVS total score was positively correlated with the ALS progression, as measured by the monthly change in the revised ALS functional rating scale. The ePVS basal ganglia regional score was inversely correlated with muscle strength. Additionally, both the ePVS score and the DTI-ALPS index were associated with regional grey matter volumes of the superior frontal gyrus and middle frontal gyrus, and the DTI-ALPS index was associated with diffusion parameters of the corticostriatal and corticothalamic tracts. This study underscores the importance of PVS dysfunction in ALS according to the ePVS and a reduced DTI-ALPS index, which were respectively associated with disease progression, neurological deficits, including reduced muscle strength, and cortical and subcortical structural changes.},
}

@article {pmid41306156,
year = {2025},
author = {Pereira de Oliveira, M and Lima Monteiro, F},
title = {When the Body Falls Silent: A Case Report of Amyotrophic Lateral Sclerosis.},
journal = {Cureus},
volume = {17},
number = {10},
pages = {e95427},
pmid = {41306156},
issn = {2168-8184},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting both upper and lower motor neurons, resulting in muscle weakness, atrophy, and, ultimately, respiratory failure. We present the case of a 49-year-old man who sustained a right wrist injury in January 2023, for which he sought evaluation by his general practitioner (GP). Due to an unfavorable recovery, he was referred to the emergency department (ED) in September of the same year, where the diagnostic workup was initiated. Following a series of complementary diagnostic tests, a diagnosis of ALS was established at the end of September. Electromyography demonstrated widespread denervation with both acute and chronic neurogenic changes, while complementary diagnostic studies excluded alternative etiologies. The patient subsequently began follow-up with a multidisciplinary team encompassing the various domains of ALS management over the following 17 months. Riluzole therapy was initiated. He ultimately passed away in February 2025, having demonstrated remarkable resilience throughout the course of his illness. This case highlights the devastating impact of early-onset ALS and underscores the importance of maintaining clinical suspicion when evaluating adults presenting with progressive neuromuscular symptoms. The rapid disease progression and associated psychosocial burden emphasize the critical role of multidisciplinary management, early palliative integration, and strong primary care involvement in optimizing patient and family support.},
}

@article {pmid41303511,
year = {2025},
author = {Gbadamosi, M and Romano, G and Simbula, M and Canarutto, G and Ottoboni, L and Corti, S and Feiguin, F},
title = {TDP-43 Regulates Rab4 Levels to Support Synaptic Vesicle Recycling and Neuromuscular Connectivity in Drosophila and Human ALS Models.},
journal = {International journal of molecular sciences},
volume = {26},
number = {22},
pages = {},
pmid = {41303511},
issn = {1422-0067},
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; *Synaptic Vesicles/metabolism ; Humans ; *Neuromuscular Junction/metabolism ; Motor Neurons/metabolism ; *Drosophila Proteins/metabolism/genetics ; *DNA-Binding Proteins/metabolism/genetics ; Disease Models, Animal ; *rab4 GTP-Binding Proteins/metabolism/genetics ; Microtubule-Associated Proteins/metabolism/genetics ; Drosophila melanogaster/metabolism ; Induced Pluripotent Stem Cells/metabolism ; Drosophila ; },
abstract = {The pathological loss of nuclear TDP-43 is a hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), leading to extensive alterations in RNA metabolism and a broad number of neuronal transcripts. However, the key effectors linking TDP-43 dysfunction to synaptic defects remain unclear. In this study, using Drosophila and human iPSC-derived motoneurons, we identify Rab4 as a direct and conserved target of TDP-43, whose expression is necessary and sufficient to recover synaptic vesicle recycling, neuromuscular junction growth, and locomotor function in TDP-43-deficient motoneurons. Moreover, Rab4 activity promotes the presynaptic recruitment of futsch/MAP1B, a microtubule-associated protein also regulated by TDP-43, which autonomously supports synaptic growth and vesicle turnover. Together, these findings define a TDP-43/Rab4/futsch/MAP1B regulatory axis that couples endosomal dynamics to cytoskeletal assembly. Furthermore, this functionally coherent module provides a mechanistic basis for understanding how synaptic vulnerability is amplified in disease and offers a framework to identify key compensatory targets capable of sustaining neuronal function in the absence of TDP-43.},
}

Animals
*Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology
*Synaptic Vesicles/metabolism
Humans
*Neuromuscular Junction/metabolism
Motor Neurons/metabolism
*Drosophila Proteins/metabolism/genetics
*DNA-Binding Proteins/metabolism/genetics
Disease Models, Animal
*rab4 GTP-Binding Proteins/metabolism/genetics
Microtubule-Associated Proteins/metabolism/genetics
Drosophila melanogaster/metabolism
Induced Pluripotent Stem Cells/metabolism
Drosophila

@article {pmid41303502,
year = {2025},
author = {Hassan, M and Shahzadi, S and Moustafa, AA and Kloczkowski, A},
title = {Neurodegeneration Through the Lens of Bioinformatics Approaches: Computational Mechanisms of Protein Misfolding.},
journal = {International journal of molecular sciences},
volume = {26},
number = {22},
pages = {},
pmid = {41303502},
issn = {1422-0067},
support = {1R01HG012117-04/NH/NIH HHS/United States ; },
mesh = {Humans ; *Computational Biology/methods ; *Neurodegenerative Diseases/metabolism ; *Protein Folding ; Animals ; Protein Aggregates ; Protein Aggregation, Pathological/metabolism ; },
abstract = {Protein and peptide aggregation has become a prominent focus in biomedical research due to its critical role in the development of neurodegenerative diseases (NDs) and its relevance to industrial applications. Neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS) are closely associated with abnormal aggregation processes, highlighting the need for a deeper understanding of their molecular mechanisms. In recent years, a wide range of computational methods, bioinformatics tools, and curated databases have been developed to predict and analyze sequences and structures that are prone to aggregation. These in silico approaches offer valuable insights into the underlying principles of aggregation and contribute to the identification of potential therapeutic targets. This review provides a concise overview of the current bioinformatics resources and computational techniques available for studying protein and peptide aggregation, intending to guide future research efforts in the field of neurodegenerative disease modeling and drug discovery.},
}

Humans
*Computational Biology/methods
*Neurodegenerative Diseases/metabolism
*Protein Folding
Animals
Protein Aggregates
Protein Aggregation, Pathological/metabolism

@article {pmid41303337,
year = {2025},
author = {Genin, EC and Lespinasse, F and Mauri-Crouzet, A and Dupuis, L and Paquis-Flucklinger, V},
title = {SLP2/PHB Aggregates in ALS Mouse Models and Patients: Implications Beyond CHCHD10-Associated Motor Neuron Disease.},
journal = {International journal of molecular sciences},
volume = {26},
number = {22},
pages = {},
pmid = {41303337},
issn = {1422-0067},
support = {FRM: MND202004011475//Fondation pour la Recherche Médicale/ ; },
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics ; Humans ; Mice ; Disease Models, Animal ; Motor Neurons/metabolism/pathology ; Prohibitins ; Male ; Female ; Spinal Cord/metabolism/pathology ; Protein Aggregates ; Mice, Transgenic ; Hippocampus/metabolism/pathology ; Aged ; Middle Aged ; *Membrane Proteins/metabolism/genetics ; Frontotemporal Dementia/metabolism/genetics/pathology ; *Repressor Proteins/metabolism/genetics ; RNA-Binding Protein FUS/genetics/metabolism ; Superoxide Dismutase-1/genetics/metabolism ; Mutation ; C9orf72 Protein/genetics ; *Protein Aggregation, Pathological/metabolism ; Mitochondrial Proteins ; },
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder characterized by motor neuron (MN) degeneration, frequently overlapping with frontotemporal dementia (FTD). Protein aggregation is a hallmark of these disorders, yet the role of aggregates in ALS pathogenesis remains unclear. Previously, stomatin-like protein 2 (SLP2) and prohibitin (PHB) aggregates were identified in a model of CHCHD10-related ALS (Chchd10[S59L/+] mice). This study raises the question of the presence and possible involvement of these aggregates in ALS beyond CHCHD10-associated motor neuron disease (MND). Using immunohistofluorescence, we analyzed SLP2/PHB expression in the spinal MNs and hippocampus of two ALS mouse models: Fus[ΔNLS] and Sod1[G86R]. Additionally, post-mortem spinal cord tissues from 27 ALS and ALS-FTD patients were analyzed. SLP2/PHB aggregates were identified in spinal MNs and the hippocampus of Fus[ΔNLS] mice but not in Sod1[G86R] mice. In ALS patients, SLP2/PHB aggregation was observed in four cases, including two with C9ORF72 mutations. Interestingly, aggregates were absent in SOD1-associated ALS patients. These findings suggest that SLP2/PHB aggregation is not specific to CHCHD10 variants but may contribute to the pathogenesis of ALS from different origins. The age-related accumulation of these aggregates highlights their potential role in disease progression and as therapeutic targets. Future studies should investigate their mechanistic contributions across different ALS subtypes.},
}

Animals
*Amyotrophic Lateral Sclerosis/metabolism/pathology/genetics
Humans
Mice
Disease Models, Animal
Motor Neurons/metabolism/pathology
Prohibitins
Male
Female
Spinal Cord/metabolism/pathology
Protein Aggregates
Mice, Transgenic
Hippocampus/metabolism/pathology
Aged
Middle Aged
*Membrane Proteins/metabolism/genetics
Frontotemporal Dementia/metabolism/genetics/pathology
*Repressor Proteins/metabolism/genetics
RNA-Binding Protein FUS/genetics/metabolism
Superoxide Dismutase-1/genetics/metabolism
Mutation
C9orf72 Protein/genetics
*Protein Aggregation, Pathological/metabolism
Mitochondrial Proteins

@article {pmid41302657,
year = {2025},
author = {Singh, A and Zeig-Owens, R and Cannon, MF and Moline, T and Schwartz, T and Prezant, DJ},
title = {Amyotrophic Lateral Sclerosis (ALS)-Related Mortality Among World Trade Center-Exposed and Non-World Trade Center-Exposed Rescue and Recovery Workers.},
journal = {International journal of environmental research and public health},
volume = {22},
number = {11},
pages = {},
pmid = {41302657},
issn = {1660-4601},
support = {U01 OH011309/OH/NIOSH CDC HHS/United States ; U01 OH011934/OH/NIOSH CDC HHS/United States ; 200-2011-39383/OH/NIOSH CDC HHS/United States ; 200-2011-39378/OH/NIOSH CDC HHS/United States ; 200-2017-93426/OH/NIOSH CDC HHS/United States ; 200-2017-93326/OH/NIOSH CDC HHS/United States ; 75D301-22-P-15204/OH/NIOSH CDC HHS/United States ; 75D301-22-R-72142/OH/NIOSH CDC HHS/United States ; 75D301-22-R-72244/OH/NIOSH CDC HHS/United States ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/mortality ; Middle Aged ; Adult ; *September 11 Terrorist Attacks ; Male ; *Occupational Exposure/adverse effects ; Female ; Aged ; Young Adult ; Adolescent ; *Rescue Work/statistics & numerical data ; New York City/epidemiology ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a rare but fatal neurodegenerative disease. Some occupational exposures are associated with ALS. This study evaluated ALS mortality rates in World Trade Center (WTC)-exposed and non-WTC-exposed rescue/recovery workers. Fire department workers who were 18-70 years old on 11 September 2001 (9/11) were included in the study (N = 33,122). Follow-up began on the later of 9/11 or on their hire date, and ended at the earliest death date or 31 December 2023. Cause of death data were obtained from the National Death Index; ALS (specifically motor neuron disease)-related mortality was the primary outcome. Demographic data were obtained from the fire departments' databases. We estimated standardized mortality ratios (SMRs) and 95% CIs for ALS-related mortality in WTC-exposed and non-WTC-exposed workers using US population rates as a reference. Multivariable-adjusted Poisson regression models estimated relative rates (RRs) and 95% CIs for ALS-related mortality in the WTC-exposed vs. non-WTC-exposed groups. Between 9/11 and 31 December 2023, five WTC-exposed and sixteen non-WTC-exposed participants died of ALS. ALS mortality rates were lower in WTC-exposed than in non-WTC-exposed rescue/recovery workers (RR = 0.54, 95% CI = 0.49-0.60). ALS-related mortality was not elevated in WTC-exposed (SMR = 0.44, 95% CI = 0.14-1.03) or non-WTC-exposed rescue/recovery workers (SMR = 1.06, 95% CI = 0.60-1.72) compared with the US general population. This initial evaluation of ALS in WTC-exposed workers indicates that the risk of ALS death is not increased in this population.},
}

Humans
*Amyotrophic Lateral Sclerosis/mortality
Middle Aged
Adult
*September 11 Terrorist Attacks
Male
*Occupational Exposure/adverse effects
Female
Aged
Young Adult
Adolescent
*Rescue Work/statistics & numerical data
New York City/epidemiology

@article {pmid41302575,
year = {2025},
author = {Batterman, S and Islam, MK and Goutman, S},
title = {Development of Life Course Exposure Estimates Using Geospatial Data and Residence History.},
journal = {International journal of environmental research and public health},
volume = {22},
number = {11},
pages = {},
pmid = {41302575},
issn = {1660-4601},
support = {1K23ES027221-02/NH/NIH HHS/United States ; 1R01ES030049-03/NH/NIH HHS/United States ; 1R01NS127188-03/NH/NIH HHS/United States ; 1P30TW017885-03/NH/NIH HHS/United States ; },
mesh = {Humans ; *Environmental Exposure/analysis ; Middle Aged ; Male ; *Amyotrophic Lateral Sclerosis/epidemiology ; Adult ; Female ; Particulate Matter/analysis ; *Air Pollutants/analysis ; Aged ; Cohort Studies ; Soot/analysis ; Spatial Analysis ; Vehicle Emissions/analysis ; Geographic Information Systems ; },
abstract = {Life course exposure estimates developed using geospatial datasets must address issues of individual mobility, missing and incorrect data, and incompatible scaling of the datasets. We propose methods to assess and resolve these issues by developing individual exposure histories for an adult cohort of patients with amyotrophic lateral sclerosis (ALS) and matched controls using residence history and PM2.5, black carbon, NO2, and traffic intensity estimates. The completeness of the residence histories was substantially improved by adding both date and age questions to the survey and by accounting for the preceding and following residence. Information for the past five residences fully captured a 20-year exposure window for 95% of the cohort. A novel spatial multiple imputation approach dealt with missing or incomplete address data and avoided biases associated with centroid approaches. These steps boosted the time history completion to 99% and the geocoding success to 92%. PM2.5 and NO2, but not black carbon, had moderately high agreement with observed data; however, the 1 km resolution of the pollution datasets did not capture fine scale spatial heterogeneity and compressed the range of exposures. This appears to be the first study to examine the mobility of an older cohort for long exposure windows and to utilize spatial imputation methods to estimate exposure. The recommended methods are broadly applicable and can improve the completeness, reliability, and accuracy of life course exposure estimates.},
}

Humans
*Environmental Exposure/analysis
Middle Aged
Male
*Amyotrophic Lateral Sclerosis/epidemiology
Adult
Female
Particulate Matter/analysis
*Air Pollutants/analysis
Aged
Cohort Studies
Soot/analysis
Spatial Analysis
Vehicle Emissions/analysis
Geographic Information Systems

@article {pmid41302089,
year = {2025},
author = {Anjum, F and Hulbah, MJ and Shamsi, A and Mohammad, T},
title = {Exploring TANK-Binding Kinase 1 in Amyotrophic Lateral Sclerosis: From Structural Mechanisms to Machine Learning-Guided Therapeutics.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {11},
pages = {},
pmid = {41302089},
issn = {2075-1729},
support = {KSRG-2024-446//King Salman Center for Disability Research/ ; },
abstract = {TANK-binding kinase 1 (TBK1) has emerged as one of the most compelling genetic contributors to amyotrophic lateral sclerosis (ALS), with heterozygous loss-of-function and pathogenic missense variants identified in patients across the ALS-frontotemporal dementia (FTD) spectrum. TBK1 participates in various core cellular processes associated with motor neuron vulnerability, including autophagy, mitophagy, and innate immune regulation, indicating that TBK1 is likely a key determinant of ALS pathogenesis. Structurally, TBK1 exhibits a trimodular organization comprising a kinase domain, a ubiquitin-like domain, and a scaffold/dimerization domain. Multiple experimentally resolved conformations and inhibitor-bound complexes provide a foundation for structure-guided therapeutic design. Here, we synthesize current genetic and mechanistic evidence linking TBK1 dysfunction to ALS, emphasizing its dual roles in autophagy and neuroinflammation. We also summarize advances in structure-based and AI-assisted drug discovery approaches targeting TBK1. Finally, we outline key translational challenges, including isoform selectivity, biomarker validation, and central nervous system (CNS) delivery, highlighting TBK1 as a promising yet complex therapeutic target in ALS. By integrating computational modeling, machine learning frameworks, and experimental pharmacology, future research may accelerate the translation of TBK1 modulators into clinically effective therapies.},
}

@article {pmid41300833,
year = {2025},
author = {Bai, R and Cheng, Z and Diao, Y},
title = {SLC30A3 as a Zinc Transporter-Related Biomarker and Potential Therapeutic Target in Alzheimer's Disease.},
journal = {Genes},
volume = {16},
number = {11},
pages = {},
pmid = {41300833},
issn = {2073-4425},
support = {2020NZ010008//the major and Special Projects of Fujian Province/ ; 2022C006R//High level Talent Innovation and Entrepreneurship Project of Quanzhou/ ; },
mesh = {Humans ; *Alzheimer Disease/genetics/metabolism/drug therapy ; *Cation Transport Proteins/genetics/metabolism ; Biomarkers/metabolism ; *Zinc/metabolism ; Transcriptome ; Gene Regulatory Networks ; Gene Expression Profiling ; },
abstract = {BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder with unclear pathogenic mechanisms. Dysregulated zinc metabolism contributes to AD pathology. This study aimed to identify zinc metabolism-related hub genes to provide potential biomarkers and therapeutic targets for AD.

METHODS: We performed an integrative analysis of multiple transcriptomic datasets from AD patients and normal controls. Differentially expressed genes and weighted gene co-expression network analysis (WGCNA) were combined to identify hub genes. We then conducted Gene Set Enrichment Analysis (GSEA), immune cell infiltration analysis (CIBERSORT), and receiver operating characteristic (ROC) curve analysis to assess the hub gene's biological function, immune context, and diagnostic performance. Drug-gene interactions were predicted using the DrugBank database.

RESULTS: We identified a single key zinc transporter-related hub gene, SLC30A3, which was significantly downregulated in AD and demonstrated potential diagnostic value (AUC 0.70-0.80). Lower SLC30A3 expression was strongly associated with impaired synaptic plasticity (long-term potentiation, long-term depression, calcium signaling pathway, and axon guidance), mitochondrial dysfunction (the citrate cycle and oxidative phosphorylation), and pathways common to major neurodegenerative diseases (Parkinson's disease, AD, Huntington's disease, and amyotrophic lateral sclerosis). Furthermore, SLC30A3 expression correlated with specific immune infiltrates, particularly the microglia-related chemokine CX3CL1. Zinc chloride and zinc sulfate were identified as potential pharmacological modulators.

CONCLUSIONS: Our study systematically identifies SLC30A3 as a novel biomarker in AD, linking zinc dyshomeostasis to synaptic failure, metabolic impairment, and neuroimmune dysregulation. These findings offer a new basis for developing targeted diagnostic and therapeutic strategies for AD.},
}

Humans
*Alzheimer Disease/genetics/metabolism/drug therapy
*Cation Transport Proteins/genetics/metabolism
Biomarkers/metabolism
*Zinc/metabolism
Transcriptome
Gene Regulatory Networks
Gene Expression Profiling

@article {pmid41300346,
year = {2025},
author = {Yeasmin, A and Torrente, MP},
title = {Histone Post-Translational Modifications and DNA Double-Strand Break Repair in Neurodegenerative Diseases: An Epigenetic Perspective.},
journal = {Biology},
volume = {14},
number = {11},
pages = {},
pmid = {41300346},
issn = {2079-7737},
support = {1R15NS125394-01/NH/NIH HHS/United States ; },
abstract = {DNA damage is a hallmark of the fatal process of neurodegeneration in the central nervous system (CNS). As neurons are terminally differentiated, they accumulate metabolic and oxidative burdens over their whole life span. Unrepaired DNA develops into DNA double-strand breaks (DSBs), which are repaired through homologous recombination (HR) or non-homologous end joining (NHEJ). Being post-mitotic and unable to normally undergo HR, damage and defective repair is especially burdensome to CNS neurons. Current research has not produced treatment to prevent and halt progression of neurodegeneration. Hence, novel targeting strategies are desperately needed. Recent investigations in histone post-translational modifications (PTMs) reveal new mechanistic insight and highlight unexplored targets to ameliorate neurodegeneration. As various histone PTMs dictate and facilitate DSB repair, they represent an underexploited area in investigating DNA damage and incorrect repair aiding neurodegeneration. Here, we review the histone PTM alterations in several neurodegenerative diseases: Amyotrophic Lateral Sclerosis/Frontotemporal Dementia, Parkinson's Disease, Alzheimer's Diseases, Multiple Sclerosis, and Huntington's Disease. These findings emphasize that histone PTM alterations can enable an aberrant DNA damage response (DDR) leading to neurodegeneration. Further research into the connections between histone PTMs and DNA damage in decaying neurons will illuminate novel targets to dampen the aberrant DDR and promote neuronal survival.},
}

@article {pmid41299417,
year = {2025},
author = {Wang, J and Zhu, M and Smith, RD},
title = {Prevalence, incidence and risk factors of syphilis among men who have sex with men in China from 2013 to 2025: a systematic review and meta-analysis.},
journal = {BMC infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12879-025-12176-8},
pmid = {41299417},
issn = {1471-2334},
abstract = {BACKGROUND: Syphilis has re-emerged in China in recent decades, particularly among men who have sex with men (MSM). We aimed to assess the prevalence, incidence, and associated factors of syphilis among MSM in China.

METHODS: We systematically searched major English (MEDLINE via PubMed, Web of Science, Embase, Scopus, Cochrane Library) and Chinese (CNKI, Wanfang, CBM, VIP, Airiti Library) databases for studies on syphilis prevalence or incidence among MSM in China published from January 1, 2013 to March 1, 2025. Study qualities were evaluated using the Hoy et al.'s risk-of-bias tool and the Newcastle-Ottawa Scale. Random-effects meta-analysis models were used to estimate pooled syphilis prevalence (%) and incidence (per 100 person-years, PYs) with 95% confidence intervals (CIs). Meta-regression analyses were performed to assess differences across subgroups.

RESULTS: A total of 441 studies (429 prevalence and 33 incidence) were included. The pooled syphilis prevalence among general MSM was 8.8% (95% CI: 8.3-9.4). Study location (R²=0.13) and study year (R²=0.11) each contributed significantly to the high heterogeneity observed (I² = 98.5%) among the general MSM prevalence studies. MSM with high-risk sexual behaviors or related risk factors exhibited higher prevalence. The pooled incidence among all MSM was 7.8 per 100 PYs (95% CI: 6.0-9.8), with similarly high heterogeneity (I² = 96.4%). Both syphilis prevalence and incidence declined over time.

CONCLUSION: Syphilis prevalence and incidence remain high among high-risk MSM subgroups in China. More rigorous studies and targeted interventions are needed to obtain more accurate estimates and to further reduce syphilis infection rates.},
}

@article {pmid41298695,
year = {2025},
author = {Almaguer-Mederos, LE and Key, J and Sen, NE and Canet-Pons, J and Döring, C and Meierhofer, D and Gispert-Sánchez, S and Cuello-Almarales, D and Almaguer-Gotay, D and Osorio-González, LM and Aguilera-Rodríguez, R and Medrano-Montero, J and Auburger, G},
title = {Multiomics approach identifies SERPINB1 as candidate biomarker for spinocerebellar ataxia type 2.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {42559},
pmid = {41298695},
issn = {2045-2322},
mesh = {Animals ; Humans ; Biomarkers/blood/metabolism ; Mice ; *Spinocerebellar Ataxias/metabolism/genetics/blood ; Proteomics/methods ; Male ; Ataxin-2/genetics/metabolism ; Female ; *Serpins/blood/genetics/metabolism ; Cerebellum/metabolism ; Spinal Cord/metabolism ; Disease Models, Animal ; Middle Aged ; Multiomics ; },
abstract = {Spinocerebellar ataxia type 2 (SCA2) is a polyglutamine disorder, and variants in its disease protein Ataxin-2 act as modifiers in the progression of Amyotrophic Lateral Sclerosis. There are no reliable molecular biomarkers for SCA2. The aim of this study was to define novel molecular biomarker candidates for SCA2. Using cerebellar and cervicothoracic spinal cord RNA/protein from Atxn2-CAG100-KnockIn (KIN) and wildtype mice, a multi-omics study was conducted based on the integration of global transcriptomic, proteomic, and phosphoproteomic data, followed by validation in mice and humans. Venn diagram comparisons across all OMICS datasets indicated that only Serpinb1a-transcript, SERPINB1A-protein and -phosphopeptides were consistently downregulated at terminal stage in 14-month-old KIN mice. Expression studies in cerebellum and spinal cord from 10 weeks (pre-manifest), 6-month-old (early ataxic), and 14-month-old (late ataxic stage) mice confirmed this progressive decrease at mRNA and protein level. SERPINB1 plasma levels were significantly lower in early-stage SCA2 patients, and displayed a significant association with the CAG repeat length at expanded ATXN2 alleles, the age at onset and INAS count. However, these human data from this SCA2 founder population were not robust, so reappraisal in large international studies and at later disease stages of SCA2 is needed. SERPINB1 was identified as novel candidate progression biomarker for SCA2 pathomechanisms.},
}

Animals
Humans
Biomarkers/blood/metabolism
Mice
*Spinocerebellar Ataxias/metabolism/genetics/blood
Proteomics/methods
Male
Ataxin-2/genetics/metabolism
Female
*Serpins/blood/genetics/metabolism
Cerebellum/metabolism
Spinal Cord/metabolism
Disease Models, Animal
Middle Aged
Multiomics

@article {pmid41298366,
year = {2025},
author = {Rizuan, A and Shenoy, J and Mohanty, P and Dos Passos, PM and Mercado Ortiz, JF and Bai, L and Viswanathan, R and Zaborowksy, J and Wang, SH and Johnson, V and Mamede, LD and Titus, AR and Ayala, YM and Ghirlando, R and Mittal, J and Fawzi, NL},
title = {Structural details of helix-mediated multimerization of the conserved region of TDP-43 C-terminal domain.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {10528},
pmid = {41298366},
issn = {2041-1723},
support = {R01 NS114289/NS/NINDS NIH HHS/United States ; R01 NS116176/NS/NINDS NIH HHS/United States ; R01NS114289//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R01NS116176//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; },
mesh = {*DNA-Binding Proteins/chemistry/metabolism/genetics ; Humans ; Molecular Dynamics Simulation ; Amyotrophic Lateral Sclerosis/genetics/metabolism ; Protein Domains ; *Protein Multimerization ; Magnetic Resonance Spectroscopy ; Mutation ; Conserved Sequence ; Protein Conformation, alpha-Helical ; },
abstract = {Pathological inclusions of the C-terminal domain (CTD) of TAR DNA binding protein-43 (TDP-43) are neurodegenerative hallmarks in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, yet CTD's aggregation propensity complicates structural characterization of native TDP-43. Here we propose structural models for the physiological multimerization of TDP-43 CTD's conserved region (CR) essential for TDP-43 RNA processing. Using NMR spectroscopy, we establish that the native state of TDP-43 CR at physiological conditions is α-helical. Hydrophobic residues drive CR helix-helix assembly, phase separation, and TDP-43 nuclear retention, while polar residues down regulate these processes. An integrative approach combining analytical ultracentrifugation, NMR-derived contacts, AlphaFold2-Multimer modeling, and all-atom molecular dynamics simulations together suggest that TDP-43 CR forms dynamic, multimeric helical assemblies stabilized by a methionine-rich core with specific contributions from a tryptophan/leucine pair. These structures show how ALS-associated mutations disrupt TDP-43 function and provide pharmacologically targetable structures to prevent its conversion into pathogenic β-sheet aggregates.},
}

*DNA-Binding Proteins/chemistry/metabolism/genetics
Humans
Molecular Dynamics Simulation
Amyotrophic Lateral Sclerosis/genetics/metabolism
Protein Domains
*Protein Multimerization
Magnetic Resonance Spectroscopy
Mutation
Conserved Sequence
Protein Conformation, alpha-Helical

@article {pmid41298223,
year = {2025},
author = {Lin, CY and Lee, BC and Zhang, PH and Lu, SC and Chang, WZ and Wang, CC and Tsai, HJ},
title = {A 16-amino acid peptide delays the progression of motor neuron degeneration and pathogenic symptoms in ALS models.},
journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics},
volume = {},
number = {},
pages = {e00806},
doi = {10.1016/j.neurot.2025.e00806},
pmid = {41298223},
issn = {1878-7479},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive motor neurons (MNs) degenerative disease. Despite advancements in understanding ALS pathogenesis, drug development lags far behind. The reduced secretion of phosphoglycerate kinase 1 (Pgk1) by NogoA-overexpressing muscle cells inhibits neurite outgrowth of MNs (NOMNs). However, administration of extracellular Pgk1 (ePgk1) reduces phospho-Cofilin (p-Cofilin), a growth cone collapse marker, and mitigates MN degeneration. This improves NOMNs in NSC34 neural cells and locomotion in SOD1-G93A ALS-mice by suppressing the p-P38-T180/p-MK2-T334/p-Limk1-S323/p-Cofilin-S3 signaling pathway. Here, we identified two Pgk1-based 16-amino acid (aa) short peptides, FD-1 and FD-2, with neuroprotective effects equivalent to those of full-length ePgk1. Administration of FD-1 or FD-2 (FD-1/-2) reduced p-Cofilin and promoted NOMNs in NSC34 cells cultured in conditioned medium obtained from NogoA-overexpressing muscle cells. Furthermore, we found that exogenous addition of FD-1/-2 to the culture medium attenuated the accumulation of phospho-Tau-S396 and the cytoplasmic mislocalization of transactive response DNA binding protein of 43 kDa (TDP-43) in oxidative-stressed ALS-like SOD1-G93A NSC34 cells. In FD-1/-2-injected zebrafish embryos, we observed increased caudal primary MNs branching. In C9orf72-knockdown and hTDP-43-G348C mRNA overexpressing zebrafish embryos injected with FD-1/-2, axonal growth and motor function were rescued. Moreover, intravenous injection of FD-1/-2 in SOD1-G93A ALS-mice delayed denervation of neuromuscular junction, preserved cell bodies of MNs in the ventral horn of spinal cord, increased grip strength, improved locomotion and prolonged survival. Therefore, both 16-aa short FD peptides are functionally equivalent to full-length 417-aa ePgk1 and thus promising therapeutic short peptides for the treatment of ALS.},
}

@article {pmid41297670,
year = {2025},
author = {Matsumoto, C and Kabuta, T and Sano, T and Murayama, S and Saito, Y and Takahashi, Y},
title = {ERBB4 colocalizes with phosphorylated tau aggregates in multiple tauopathies.},
journal = {Neurochemistry international},
volume = {192},
number = {},
pages = {106093},
doi = {10.1016/j.neuint.2025.106093},
pmid = {41297670},
issn = {1872-9754},
abstract = {The neuregulin-ERBB4 pathway is essential for maintaining cellular function. Upon stimulation by its ligand, neuregulin, ERBB4-a receptor tyrosine kinase-triggers multiple cellular responses, including proliferation, apoptosis, differentiation, and neuromuscular junction formation. Previous research has implicated dysregulated ERBB4 signaling in the pathophysiology of several neurodegenerative disorders, such as Alzheimer's disease, progressive supranuclear palsy, amyotrophic lateral sclerosis, and Parkinson's disease. In this study, we examined ERBB4 expression in diseases characterized by phosphorylated tau (MAPT) pathology. We found that ERBB4 colocalized with neuronal and glial phosphorylated tau-positive inclusions in multiple tauopathies, including Pick's disease, Alzheimer's disease, corticobasal degeneration, progressive supranuclear palsy, argyrophilic grain disease, and frontotemporal lobar degeneration with MAPT mutation. Conversely, ERBB4 did not colocalize with α-synuclein aggregates in α-synucleinopathies (Parkinson's disease and multiple system atrophy) or with neuronal intranuclear inclusions in triplet repeat disorders (Huntington's disease and dentatorubral-pallidoluysian atrophy). A co-immunoprecipitation assay indicated that ERBB4 can interact with tau intracellularly. Notably, in corticobasal degeneration, we observed ectopic ERBB4 expression in astrocytes lacking apparent phosphorylated tau aggregates. These findings suggest a potential role for ERBB4 in the pathophysiology of tau-related neurodegenerative diseases.},
}