@article {pmid41674784,
year = {2025},
author = {Yashooa, RK and Nabi, AQ and Smail, SW and Azeez, SS and Nooh, WA and Mustafa, SA and Al-Farha, AA and Capitanio, N and Shekha, MS},
title = {CRISPR-Cas technologies in neurodegenerative disorders: mechanistic insights, therapeutic potential, and translational challenges.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1737468},
pmid = {41674784},
issn = {1664-2295},
abstract = {CRISPR-Cas genome-editing technologies have emerged as powerful tools for precise DNA and RNA modulation, offering promising therapeutic strategies for neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). This review critically evaluates current CRISPR/Cas applications in neurodegeneration, with emphasis on mechanistic insights, therapeutic outcomes, and translational feasibility. Preclinical and early translational studies demonstrate that CRISPR-Cas platforms can correct pathogenic mutations, suppress toxic gene expression, and restore neuronal function. Advanced modalities, including base and prime editing, CRISPRi/a, and RNA-targeting Cas systems, improve precision and reduce genomic damage, which is particularly advantageous in post-mitotic neurons. Emerging CRISPR-based diagnostics (e.g., SHERLOCK and DETECTR), AI-assisted sgRNA design, and machine-learning approaches for predicting off-target effects further enhance the safety, stratification, and monitoring of CRISPR therapeutics. In parallel, patient-derived brain organoids and assembloids provide scalable human-relevant platforms for mechanistic studies and preclinical validation. Despite this progress, major challenges remain, including efficient delivery across the blood-brain barrier, immune responses, long-term safety, and ethical and regulatory considerations. Overall, CRISPR-Cas technologies hold strong potential as disease-modifying interventions for neurodegenerative disorders, provided that advances in delivery systems, artificial intelligence integration, and regulatory oversight continue to evolve toward clinical translation.},
}

@article {pmid41674718,
year = {2025},
author = {Qin, X and Liao, L},
title = {Graph transformer with disease subgraph positional encoding for improved comorbidity prediction.},
journal = {Quantitative biology (Beijing, China)},
volume = {13},
number = {4},
pages = {e70008},
pmid = {41674718},
issn = {2095-4697},
abstract = {Comorbidity, the co-occurrence of multiple medical conditions in a single patient, profoundly impacts disease management and outcomes. Understanding these complex interconnections is crucial, especially in contexts where comorbidities exacerbate outcomes. Leveraging insights from the human interactome and advancements in graph-based methodologies, this study introduces transformer with subgraph positional encoding (TSPE) for disease comorbidity prediction. Inspired by biologically supervised embedding, TSPE employs transformer's attention mechanisms and subgraph positional encoding (SPE) to capture interactions between nodes and disease associations. Our proposed SPE proves more effective than Laplacian positional encoding, as used in Dwivedi et al.'s graph transformer, underscoring the importance of integrating clustering and disease-specific information for improved predictive accuracy. Evaluated on real clinical benchmark datasets (RR0 and RR1), TSPE demonstrates substantial performance enhancements over the state-of-the-art method, achieving up to 28.24% higher ROC AUC (receiver operating characteristic-area under the curve) and 4.93% higher accuracy. This method shows promise for adaptation to other complex graph-based tasks and applications. The source code is available at GitHub website (xihan-qin/TSPE-GraphTransformer).},
}

@article {pmid41674618,
year = {2026},
author = {Xu, H and Petrozziello, T and Boudi, A and Shibata, S and Huntress, SS and Shahryari, A and Zhao, X and Kesavan, M and Granucci, EJ and Castillo Torres, AL and Monsanto, RZB and Lemanski, J and Jana, B and De Esch, CEF and Cudkowicz, ME and Berry, JD and , and Brand, H and Talkowski, ME and Mouro Pinto, R and Gao, D and Sadri-Vakili, G},
title = {Transcriptomic profiling uncovers mis-splicing and gene fusions in amyotrophic lateral sclerosis.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.02.05.26345503},
pmid = {41674618},
abstract = {Advances in transcriptomics have transformed our understanding of amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease, revealing disrupted gene expression profiles and highlighting the multi-system biology of ALS. Despite major advances, transcriptomic studies have only begun to capture the complexity and the molecular hierarchy of transcriptomic alterations in ALS. To resolve and characterize the transcriptome in ALS, we performed a comprehensive reanalysis of bulk RNA sequencing from the New York Genome Center ALS Consortium cohort across five post-mortem tissues including motor and frontal cortex, cervical and lumbar spinal cord, and cerebellum. By deploying dual analytical pipelines - one reference-based to model canonical events and one de novo to detect transcript structural novelties - we disentangled the quantitative and qualitative architectures of ALS. Our reference-based analysis revealed that ALS transcriptome is defined primarily by splicing failure rather than changes in gene expression. Aberrant splicing events, particularly intron retention, outnumbered differentially expressed genes by an order of magnitude. This widespread loss of fidelity disproportionately affected RNA-binding proteins, suggesting a collapse in their autoregulatory feedback loops. Deconvolution of these signals identified distinct cellular vulnerabilities: transcriptional disruptions were enriched in glial cells in sporadic cases but in neuronal cells in C9ORF72-positive cases. Furthermore, we observed sex-specific dysregulation, with male patients exhibiting greater disruption in guanosine triphosphatase signaling and ciliary organization pathways. In parallel, our de novo analysis uncovered a significant burden of disease-specific gene fusions that were absent in controls. Whole-genome sequencing of the same individuals, together with a larger reference population confirmed that disease-specific fusions do not arise from genomic structural variants, indicating a transcriptional rather than genomic origin. Investigation into the mechanism of these RNA-based fusions revealed a critical deviation in splice site definition: while canonical splice junctions exhibit a high density of binding motifs for polyA-binding or 3'-cleaveage proteins approximately 50 base pairs upstream of the splice donor site (left junction), ALS-specific fusion junctions displayed a dramatic depletion of these motifs in the same region. Functionally, the presence of these sparse disease-specific fusions was strongly correlated with severe splicing outliers in genes governing guanosine triphosphatase activity, converging with the tissue- and male-specific defects identified in our reference-based analysis. Altogether, our results delineated a transcriptome characterized by aberrant splicing with tissue-and sex-specific changes and identified structural-variant-independent RNA fusions as candidate disease modifiers that may amplify pathology. This integrated view provides a mechanistic scaffold for splicing-centered and RNA-structural therapeutic strategies for ALS.},
}

@article {pmid41674118,
year = {2026},
author = {Sun, S and Xin, J and Zhang, Y and Yang, B and Su, D and Ni, R and Ma, Q and Li, N and Ma, G and Peng, Q and Chen, S and Prehn, JHM and Tam, KY and Wang, H and Ying, Z},
title = {p62/SQSTM1 Condensation Modulates Mitochondrial Clustering to Participate in Mitochondrial Quality Control.},
journal = {Aging cell},
volume = {25},
number = {2},
pages = {e70402},
doi = {10.1111/acel.70402},
pmid = {41674118},
issn = {1474-9726},
support = {32471048//National Natural Science Foundation of China/ ; 32371018//National Natural Science Foundation of China/ ; 82022022//National Natural Science Foundation of China/ ; 82071274//National Natural Science Foundation of China/ ; BM2013003//Jiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases/ ; 23KJA310005//Natural Science Foundation of Jiangsu Provincial Higher Education Institutions/ ; YXY2301006//Interdisciplinary Basic Frontier Innovation Program of Suzhou Medical College of Soochow University/ ; //Suzhou International Joint Laboratory for Diagnosis and Treatment of Brain Diseases/ ; //Priority Academic Program Development of the Jiangsu Higher Education Institutes (PAPD)/ ; 0062/2021/A//Science and Technology Development Fund/ ; MYRG2022-00171-FHS//the University of Macau/ ; },
mesh = {*Sequestosome-1 Protein/metabolism/genetics ; *Mitochondria/metabolism ; Humans ; Mitophagy ; Ubiquitin-Protein Ligases/metabolism ; },
abstract = {Mitochondrial quality control is tightly associated with aging-related neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD). Previous studies reported that ALS/FTD-associated protein p62 drives "mitochondrial clustering" (perinuclear clustering of fragmented and swollen mitochondria) during PINK1/Parkin-mediated mitophagy, but the underlying molecular mechanism, especially the precise role of p62 in mitochondrial clustering during mitophagy and the potential relationship between the mitochondrial quality control mediated by p62 and disease pathogenesis of ALS/FTD, remains unclear. Here, using cell biology in combination with an optogenetic tool, we show that the phase separation (condensation) of p62 mediates the clustering of damaged mitochondria to form "grape-like" clusters during PINK1/Parkin-mediated mitophagy, which is tightly associated with aging-related neurodegenerative diseases. In addition, our data suggest this mitochondrial clustering process is an arrest mechanism driven by p62 condensation (beyond the function of other autophagy receptors in mitophagy), which acts as a "brake" to reduce the surface area of dysfunctional mitochondria within cytoplasm for minimizing mitochondrial turnover in cells. Moreover, ALS/FTD-related pathological mutations perturb p62 condensation, thereby inhibiting mitochondrial clustering and destroying the "brake" machinery of mitochondrial quality control. Together, our data highlight how p62 condensation modulates organelle quality control in cell biology, and the important role of p62 condensation in both physiology and pathology.},
}

*Sequestosome-1 Protein/metabolism/genetics
*Mitochondria/metabolism
Humans
Mitophagy
Ubiquitin-Protein Ligases/metabolism

@article {pmid41673790,
year = {2026},
author = {Zheng, W and Xu, L and Cai, J and Hou, J and Chen, L and Zhang, N and Zhan, S and Fan, D and He, J},
title = {Comprehensive clinical and genetic architecture of familial amyotrophic lateral sclerosis in China: A 15-year cohort study with 302 families.},
journal = {Neural regeneration research},
volume = {21},
number = {6},
pages = {2573-2579},
doi = {10.4103/NRR.NRR-D-24-00701},
pmid = {41673790},
issn = {1673-5374},
abstract = {JOURNAL/nrgr/04.03/01300535-202606000-00072/figure1/v/2026-02-11T151048Z/r/image-tiff The growing recognition of the role of genetics in the development of amyotrophic lateral sclerosis is evident. However, there has yet to be a comprehensive analysis of the clinical characteristics and genetics of familial amyotrophic lateral sclerosis in an Asian population. This study aimed to provide an in-depth analysis of the clinical features and genetic spectrum of familial amyotrophic lateral sclerosis over 15 years in a clinic-based cohort of patients from the Chinese mainland. Enrollment of 302 amyotrophic lateral sclerosis families from 28 provinces was undertaken from January 2008 to September 2023. A group-based trajectory model for disease progression based on amyotrophic lateral sclerosis Functional Rating Scale-Revised (ALSFRS-R) scores was validated using bootstrap internal validation in patients with familial amyotrophic lateral sclerosis, as well as patients with sporadic amyotrophic lateral sclerosis (matched at a 1:4 ratio, with replacement). DNA samples from 244 index patients were screened for variants in the pathogenic genes SOD1, FUS, TDP43, and C9ORF72, of which 146 were also subjected to genome-wide next-generation sequencing. Gene-level burden analysis was used to evaluate the distribution of rare variants in the cohort. We found that rapid dynamic disease progression was associated with an older age at onset, shorter diagnostic delay, lower body mass index, bulbar onset, and ≥ 1 affected first-degree relative. Certain attributes, such as age at onset and time from onset to diagnosis, had comparable impacts on the clinical progression trajectories of both familial amyotrophic lateral sclerosis and sporadic amyotrophic lateral sclerosis. Harboring pathogenic/likely pathogenic variants in amyotrophic lateral sclerosis-causative genes reduced the age of onset of familial amyotrophic lateral sclerosis. Among the patients with familial amyotrophic lateral sclerosis, 17.8% possessed ≥ 2 pathogenic/likely pathogenic variants. Sequencing kernel association test analysis showed that the SOD1 rare variant burden (P = 1.3e-15) was associated with a significant risk of familial amyotrophic lateral sclerosis. Our findings conclusively confirmed the clinical features and genetic spectrum of familial amyotrophic lateral sclerosis over 15 years in a clinical cohort from China, contributing to a deeper understanding of genotype-phenotype relationships in familial amyotrophic lateral sclerosis. This comprehensive evaluation of specific clinical characteristics, clinical prognosis, and genetic variants of amyotrophic lateral sclerosis based on detailed clinical and genetic information may lead to the development of genotype-specific treatment approaches.},
}

@article {pmid41673769,
year = {2026},
author = {Sharma, S and Vandenakker, A and Cortés-Pérez, C and Milne, S and Douville, RN},
title = {Implications of virus-induced stress granules in tauopathies.},
journal = {Translational neurodegeneration},
volume = {15},
number = {1},
pages = {4},
pmid = {41673769},
issn = {2047-9158},
support = {#2401-3152//St. Boniface Hospital Foundation/ ; RGPIN-2016-05761//Natural Sciences and Engineering Research Council of Canada/ ; },
mesh = {Humans ; *Tauopathies/metabolism/virology/pathology ; *Stress Granules/metabolism/virology ; Animals ; *tau Proteins/metabolism ; *Virus Diseases/metabolism/complications ; },
abstract = {Tauopathies are characterized by aberrant tau structure and function, which is associated with neurodegenerative dementias, such as Alzheimer's disease, Pick's disease, and frontotemporal dementia, as well as the motor neuron disease amyotrophic lateral sclerosis. Consistent association of these neurodegenerative conditions with viruses suggests an interplay between viral activity and the development of tauopathy. In this review, we explore how tau dysregulation may facilitate viral activity, and conversely, how viruses may drive tauopathy. We further discuss how stress granules (SGs) are a likely hub for the interactions between tau and viral components, leading to tau deregulation. Within the network of SG proteins analyzed, 15 proteins were identified to be both tau interactors and implicated in viral processes, having dual functionality. These SG proteins are further discussed in terms of their relationship with tauopathy, viral replication, and neurodegeneration. Concrete examples of synergistic and competing effects between tau and viruses are highlighted, revealing both pathological and protective mechanisms. This dichotomy underscores a complexity that is both disease- and virus-specific, within the context of SG biology and tau pathology. While the viral involvement in tauopathies could be considered detrimental, it may provide insights into antiviral therapeutics to target the accumulation and misfolding of tau in these neurodegenerative diseases.},
}

Humans
*Tauopathies/metabolism/virology/pathology
*Stress Granules/metabolism/virology
Animals
*tau Proteins/metabolism
*Virus Diseases/metabolism/complications

@article {pmid41673022,
year = {2026},
author = {Ali, M and Biswas, A and Iglseder, A and Kumar, V and Kumar, S and Gupta, S and Hollaus, M and Pfeifer, N and Lohani, B},
title = {Terrestrial and Airborne Laser Scanning Dataset of Trees in the Shivalik Range, India with Field Measurements and Leaf-Wood Classifications.},
journal = {Scientific data},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41597-026-06674-w},
pmid = {41673022},
issn = {2052-4463},
support = {DST/CE/2024140//Department of Science and Technology, Ministry of Science and Technology (DST)/ ; DST/CE/2024140//Department of Science and Technology, Ministry of Science and Technology (DST)/ ; DST/CE/2024140//Department of Science and Technology, Ministry of Science and Technology (DST)/ ; },
abstract = {Annotated datasets are essential for training and evaluating machine learning models in forest ecology. This dataset provides high-resolution, annotated LiDAR point clouds of 674 individual trees from 12 forest plots in the Shivalik Range of northern Haryana, India, representing 24 species. Data were acquired using Terrestrial Laser Scanning (TLS) and Airborne Laser Scanning (ALS), include field-measured attributes such as species identity and Diameter at Breast Height (DBH), and terrestrial and aerial RGB imagery. TLS point clouds were georeferenced and co-registered with centimetre-level accuracy, enabling precise integration with ALS data. The dataset includes segmented individual trees and wood-leaf classifications, suitable for applications such as tree morphology analysis, biomass estimation, and species classification. To support benchmarking, outputs from established classification algorithms (LeWoS, TLSeparation, CANUPO, and Random Forest) are included. As one of the first open-access LiDAR datasets from Indian tropical forests, it provides critical reference data for developing and validating forest structure models. It can also aid biomass mapping efforts in support of large-scale missions such as NASA-ISRO's NISAR and ESA's BIOMASS.},
}

@article {pmid41672542,
year = {2026},
author = {Takubo, M and Matsumoto, Y and Sasaki, C and Ikeda, K and Sugeno, N and Warita, H and Aoki, M},
title = {Response to the Letter by Dr. Zarrouk et al.},
journal = {Internal medicine (Tokyo, Japan)},
volume = {},
number = {},
pages = {},
doi = {10.2169/internalmedicine.6957-25},
pmid = {41672542},
issn = {1349-7235},
}

@article {pmid41672538,
year = {2026},
author = {Zarrouk, S and Finsterer, J},
title = {SCA3 Can Manifest Phenotypically with ALS-like Characteristics.},
journal = {Internal medicine (Tokyo, Japan)},
volume = {},
number = {},
pages = {},
doi = {10.2169/internalmedicine.6851-25},
pmid = {41672538},
issn = {1349-7235},
}

@article {pmid41672134,
year = {2026},
author = {Maneu, V and García, AG},
title = {P2X7 receptors as targets for neuroprotection.},
journal = {Neuropharmacology},
volume = {289},
number = {},
pages = {110877},
doi = {10.1016/j.neuropharm.2026.110877},
pmid = {41672134},
issn = {1873-7064},
abstract = {In this review we explore the potential of P2X7 receptor blockers to elicit neuroprotection. This conjecture is based on a reasonably well-established role of this receptor in activating glial cells to maintain a chronic low-level neuroinflammatory state in the brain of patients suffering some neurodegenerative diseases (NDDs). In this context we briefly discuss evidence supporting the role of P2X7 receptors (P2X7) in the pathogenesis of Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, multiple sclerosis, and retinal degeneration. From a pathogenic point of view these diseases have specific features but all share a low level neuroinflammatory state with microglia activation and enhanced P2X7 expression. Next, we comment on available P2X7 blockers with central nervous system (CNS) target engagement. Then, we deal with the proof-of-concept concerning the potential of some blockers to mitigate the neuroinflammatory state in preclinical models of the target diseases above mentioned. We follow with a discussion of the scarce number of clinical trials done with some P2X7 blockers in inflammatory diseases. Finally, we discuss the current discrepancy between promising preclinical data and the limited number of clinical trials exploring P2X7 antagonists in NDDs. We provide some clues that may boost clinical trials with single P2X7 blockers but particularly, with their association with other medicines currently being used or that are intended to be prescribed in the treatment of NDDs.},
}

@article {pmid41672113,
year = {2026},
author = {Prova, NS and Elsayyid, MW and Tanis, JE},
title = {Superoxide dismutase impacts extracellular vesicle shedding and uptake.},
journal = {Free radical biology & medicine},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.freeradbiomed.2026.02.008},
pmid = {41672113},
issn = {1873-4596},
abstract = {Extracellular vesicles (EVs), which transfer bioactive macromolecules between cells, play a critical role in the pathogenesis of multiple neurodegenerative diseases. Focus has centered on how altered EV contents propagate disease and on the potential for EVs as diagnostic biomarkers, while the effects of pathogenic factors on EV release are poorly understood. Using a functional endogenous reporter, we showed that the key antioxidant enzyme superoxide dismutase 1 (SOD-1) is expressed in C. elegans EV-releasing neurons, localizes to the cytoplasm, and reduces levels of reactive oxygen species (ROS). We then defined how sod-1 mutations affect EV shedding from sensory neuron primary cilia into the environment, ciliary enrichment of proteins packaged into EVs, and glial uptake of EVs in vivo, by imaging C. elegans expressing fluorescent protein-tagged EV cargoes. Deletion of SOD-1, as well as the SOD-1(G85R) amyotrophic lateral sclerosis (ALS) pathogenic variant, increased EV shedding from the cilium distal tip, and this was associated with greater abundance of EV cargo in this ciliary compartment. In contrast, loss of SOD-1 reduced the glial uptake of a different EV subpopulation that is shed from the ciliary base, without affecting release into the environment. These results demonstrate that SOD-1 has a subtype-specific effect on the release of EVs with distinct signaling potentials. Intriguingly, we discovered that exposure to paraquat, which increases mitochondrial ROS, reduced the shedding of both distal tip and ciliary base-derived EVs. These opposing effects of the sod-1 mutations and paraquat treatment on EV release suggest that subcellular ROS compartmentalization may serve as a mechanism to regulate ciliary EV shedding.},
}

@article {pmid41671402,
year = {2026},
author = {Shi, M and Ge, W and Li, C and Liu, B and Deng, X and Liu, C and Zheng, M and Zhang, P and Li, L and Guo, Y and Han, Y and Yang, Y and Yu, YV and Jin, YN},
title = {Versatile CRISPR-Cas Tools for Gene Regulation in Zebrafish via an Enhanced Q Binary System.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e11485},
doi = {10.1002/advs.202511485},
pmid = {41671402},
issn = {2198-3844},
support = {32070832//National Natural Science Foundation of China/ ; 32150610476//National Natural Science Foundation of China/ ; 2042022dx0003//Fundamental Research Funds for the Central Universities/ ; },
abstract = {CRISPR-Cas systems revolutionize gene regulation across diverse organisms, including zebrafish. However, most zebrafish studies still rely on transient delivery of CRISPR components, with limited use of transgenic models, primarily restricted to Cas9-mediated knockouts. This limitation arises from challenges in achieving sustained, tissue-specific, and efficient expression of transgenic CRISPR effectors. To address these challenges, we introduce CRISPR-Q, a transgenic system that combines the QFvpr/QUAS binary expression platform with CRISPR-Cas technologies. CRISPR-Q overcomes the drawbacks of transient mRNA or protein delivery and circumvents the toxicity and transgene silencing issues associated with other binary systems, such as Gal4/UAS. The system enables robust and spatiotemporal expression of CasRx or dCas9vpr, allowing precise transcript knockdown (CRISPR-QKD) or gene activation (CRISPR-Qa). Using CRISPR-QKD, we achieve effective knockdown of smn1 and simultaneous knockdown of tardbp and tardbpl, modeling spinal muscular atrophy and amyotrophic lateral sclerosis, respectively. CRISPR-Qa activates endogenous lin28a and sox9b, demonstrating its functional versatility. We further validate CRISPR-Q's tissue-specific applicability in heart-specific transgenic zebrafish. Together, CRISPR-Q represents a robust and versatile platform for studying gene function and modeling human diseases in zebrafish, with broad potential for adaptation in other model organisms.},
}

@article {pmid41670738,
year = {2026},
author = {Thorarinsson, BL and Sveinsson, OA and Hilmarsson, A and Sigurthorsdottir, TB and Andersen, PM},
title = {Treating SOD1-ALS with tofersen results in nonprogressive chronic ALS-a case series from Iceland.},
journal = {Journal of neurology},
volume = {273},
number = {2},
pages = {140},
pmid = {41670738},
issn = {1432-1459},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/drug therapy/cerebrospinal fluid ; Male ; Iceland ; *Superoxide Dismutase-1/genetics ; Middle Aged ; Female ; Aged ; Adult ; *Oligonucleotides/therapeutic use/administration & dosage ; Mutation/genetics ; Neurofilament Proteins/cerebrospinal fluid ; *Oligonucleotides, Antisense/therapeutic use ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder. We describe four patients with hereditary ALS caused by the p.Gly94Ser SOD1 mutation who were treated monthly with the intrathecal antisense oligonucleotide tofersen in a clinical setting at Landspitali University Hospital of Iceland. After initiating treatment 15-26 months ago, no significant clinical deterioration was observed, and three patients showed signs of clinical improvement, with some recovery of motor function. All four patients currently present with chronic nonprogressive ALS, a phenotype not previously observed or documented. Concomitantly, the concentration of neurofilament light chain (Nf-L) in the cerebrospinal fluid decreased to the normal range. This clinical benefit and decrease in Nf-L levels were detected regardless of the patient's initial ALSFRS-R score. No serious adverse events were observed. Notably, we observed a clinically meaningful effect in two patients who had been ill for several years before treatment was instituted, raising questions about who should receive treatment and the biology of paresis and motor neuron cell loss in patients with ALS. Although only a minority of ALS patients carry a SOD1 mutation, the advent of this new precision medicine has profound implications for ALS management.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/drug therapy/cerebrospinal fluid
Male
Iceland
*Superoxide Dismutase-1/genetics
Middle Aged
Female
Aged
Adult
*Oligonucleotides/therapeutic use/administration & dosage
Mutation/genetics
Neurofilament Proteins/cerebrospinal fluid
*Oligonucleotides, Antisense/therapeutic use

@article {pmid41669804,
year = {2026},
author = {Nadeem, H},
title = {Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Have Distinct Prediagnostic Blood Biochemical Profiles.},
journal = {Annals of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ana.78173},
pmid = {41669804},
issn = {1531-8249},
}

@article {pmid41669799,
year = {2026},
author = {Masataka, Y and Matsumoto, T},
title = {In Response to "Concerns Regarding Masataka et al.'s 'Revisiting the Gateway Drug Hypothesis for Cannabis'".},
journal = {Neuropsychopharmacology reports},
volume = {46},
number = {1},
pages = {e70093},
pmid = {41669799},
issn = {2574-173X},
mesh = {Humans ; *Cannabis/adverse effects ; *Marijuana Smoking ; *Marijuana Use ; *Marijuana Abuse ; Japan ; },
abstract = {We clarify Dr. Narita's concerns by replacing subjective wording with data-based statements, emphasizing the descriptive-not causal-nature of our analysis, and noting that logistic regression was exploratory. Our findings show both progression and non-progression pathways, indicating no single dominant gateway pattern among Japanese cannabis users.},
}

Humans
*Cannabis/adverse effects
*Marijuana Smoking
*Marijuana Use
*Marijuana Abuse
Japan

@article {pmid41668546,
year = {2026},
author = {Lillard, AS},
title = {Why Does Fantasy in Screen Media Deplete Children's Executive Function?.},
journal = {Developmental science},
volume = {29},
number = {2},
pages = {e70143},
pmid = {41668546},
issn = {1467-7687},
support = {23-10339//Arnold Ventures/ ; },
mesh = {Humans ; *Executive Function/physiology ; *Fantasy ; Child ; Cognition/physiology ; *Television ; },
abstract = {In response to Hinten et al.'s (2025) meta-analysis of the impact of fantasy and fast pacing in screen media on young children, I present an information processing model in effort to explain the fantasy effect. Drawing on important work by Lang, I discuss how media might be processed, and why fantasy events could be particularly problematic. In essence, they may overload the cognitive system, which is trying to make sense of impossible events without the benefit of existing schemas that would reduce cognitive load. SUMMARY: We need better theory to guide research on why fantasy impairs executive function. Some ideas are provided here.},
}

Humans
*Executive Function/physiology
*Fantasy
Child
Cognition/physiology
*Television

@article {pmid41668214,
year = {2026},
author = {Cao, MC and Swanson, MEV and Basak, I and McDonald, K and Arnold, FJ and Stockford, CM and Guo, G and Curtis, MA and Faull, RLM and Hughes, SM and Spada, AR and Dragunow, M and Scotter, EL},
title = {Lost in translation: absence of KIAA1324/ELAPOR1 protein in pathological TDP-43-affected neurons in ALS/FTD.},
journal = {Acta neuropathologica communications},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40478-026-02237-7},
pmid = {41668214},
issn = {2051-5960},
support = {T32 AG000096/NH/NIH HHS/United States ; R35 NS122140/NH/NIH HHS/United States ; 865871//Muscular Dystrophy Association/ ; 23-CSDA-618//American Academy of Neurology/ ; PG12747//Robert Packard Center for ALS Research, Johns Hopkins University/ ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a movement disorder lacking effective diagnostics and therapeutics, largely due to its clinical and etiological heterogeneity. The unifying hallmark of TDP-43 pathology is found in approximately 97% of ALS patients, and 50% of frontotemporal dementia (FTD) patients. Indeed, TDP-43 has a central role in ALS/FTD disease mechanisms. An mRNA target of TDP-43 loss of function, KIAA1324/ELAPOR1, is consistently upregulated in various RNA-sequencing datasets from systems with TDP-43 depletion.

METHODS: This study sought to investigate the TDP-43 target gene, KIAA1324, in the context of human brain tissue. We performed immunohistochemistry and image analysis on 10 ALS and 10 control brains to quantify the protein levels of KIAA1324 in TDP-43 pathology-affected cells. We then used immunocytochemistry of iPSC-derived neurons and mass spectroscopy of SH-SY5Y cells to investigate the relationship between KIAA1324 mRNA and the function of its cognate protein KIAA1324.

RESULTS: KIAA1324 expression was enriched in neurons in the human brain. While KIAA1324 mRNA increased in iPSC-derived neurons with TDP-43 depleted from the nucleus in vitro, in human post-mortem brain neurons, KIAA1324 protein was significantly decreased (p < 0.05) in cells with pathological TDP-43 (nuclear-cleared TDP-43 and cytoplasmic, phosphorylated TDP-43). This may be due to the alternative polyadenylation of KIAA1324 detected with TDP-43 depletion from iPSC-derived neurons, hypothesised to affect translation efficiency. Mass spectrometry of SH-SY5Y cells revealed that overexpression of KIAA1324 protein affects a network of mitochondrial proteins.

CONCLUSIONS: The clear inverse relationship between KIAA1324 mRNA levels and TDP-43 function, and the near complete absence of KIAA1324 protein from neurons with pathological TDP-43 in post-mortem brain tissue, suggests KIAA3142 function is impaired in TDP-43 proteinopathies. Therefore, in addition to there being various disease mechanisms implicated in ALS, and TDP-43 being a challenging disease target to restore, KIAA1324 emerges as another of the many targets downstream of TDP-43 that may need to be addressed to demonstrate a therapeutic effect in ALS/FTD.},
}

@article {pmid41545942,
year = {2026},
author = {Sun, W and Luan, H and Li, S and Wang, P and Gong, J and Xu, C and Han, X and Wen, B and Lv, S and Wei, C},
title = {Circulating adipokines level and the risk of neurodegenerative diseases: a two‑sample mendelian randomization study and proteomic analysis.},
journal = {BMC neurology},
volume = {26},
number = {1},
pages = {90},
pmid = {41545942},
issn = {1471-2377},
support = {2017YFC1310103//the National Key Research and Development Program of China/ ; 2021ZD0201802//the STI2030-Major Projects/ ; },
abstract = {BACKGROUND: Observational studies have suggested associations between circulating adipokines and neurodegenerative diseases, but the causal nature of these relationships remains unclear. This study evaluated the causal effects of adipokines on neurodegenerative diseases using Mendelian randomization (MR) and validated key findings through proteomic analysis.

METHODS: Two-sample MR was performed using genome-wide association study (GWAS) summary statistics for adiponectin (N = 39,883), leptin (N = 57,232), resistin (N = 21,758), and monocyte chemoattractant protein-1 (MCP-1; N = 21,758). Outcomes included Alzheimer’s disease (AD; N = 63,926), Parkinson’s disease (PD; N = 482,730), and amyotrophic lateral sclerosis (ALS; N = 36,052). The inverse-variance weighted (IVW) method was applied for primary causal estimates, with sensitivity analyses assessing pleiotropy and heterogeneity. Significant MR findings were further examined in a proteomic cohort.

RESULTS: Higher genetically predicted adiponectin levels were significantly associated with a reduced risk of AD (odds ratio [OR] = 0.79, 95% confidence interval [CI] = 0.65–0.96, p = 0.019). This association remained robust across multiple sensitivity analyses, with no evidence of horizontal pleiotropy or heterogeneity. By contrast, no causal relationships were identified for leptin, resistin, or MCP-1 with the risk of AD, PD, or ALS. Complementing the genetic findings, proteomic analysis further revealed that plasma adiponectin levels were downregulated in mild cognitive impairment patients who experienced cognitive deterioration compared with those showing cognitive improvement.

CONCLUSION: The findings provide genetic evidence supporting a potential protective role of adiponectin in AD, with the proteomic results offering complementary, directionally consistent support. Adiponectin may represent a potential biomarker and therapeutic target for AD.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12883-026-04636-8.},
}

@article {pmid41668129,
year = {2026},
author = {Garnier, M and Gouju, J and Rousseau, A and Zidane-Marinnes, M and Scherer, C and Cassereau, J and Letournel, F and Codron, P},
title = {Exploratory assessment of phosphorylated TDP-43 immunoreactivity in minor salivary glands of patients with ALS.},
journal = {Acta neuropathologica communications},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40478-026-02251-9},
pmid = {41668129},
issn = {2051-5960},
}

@article {pmid41667820,
year = {2026},
author = {Vicencio, E and Gomez, L and Beltran, S and Hernandez, F and Rodriguez, L and Bravo, C and Jofré, T and Gálvez, F and Labrador, L and Rojas-Rivera, D and Cortés, BI and Cortez, C and Manque, P and Woehlbier, U},
title = {FAM120A - a protein inserted in the ALS disease network.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-39329-2},
pmid = {41667820},
issn = {2045-2322},
support = {11240328//Agencia Nacional de Investigación y Desarrollo/ ; 1230823//Agencia Nacional de Investigación y Desarrollo/ ; 1150743//Agencia Nacional de Investigación y Desarrollo/ ; },
}

@article {pmid41666800,
year = {2026},
author = {Maidi, AZM and Suram, RP and Deniz, Y and An, SL and Hong, Y},
title = {Heart rate variability as a non-invasive biomarker of autonomic dysfunction in amyotrophic lateral sclerosis: A systematic review and meta-analysis.},
journal = {Autonomic neuroscience : basic & clinical},
volume = {264},
number = {},
pages = {103393},
doi = {10.1016/j.autneu.2026.103393},
pmid = {41666800},
issn = {1872-7484},
abstract = {OBJECTIVE: This study assessed heart rate variability (HRV) alterations in amyotrophic lateral sclerosis (ALS) patients compared to healthy control groups using both frequency-domain and time-domain HRV parameters.

METHODS: A systematic review and meta-analysis were conducted using studies retrieved from PubMed, Embase, Web of Science, and Cochrane Library databases up to November 13, 2024. Fourteen studies were included in the qualitative synthesis and eight in the quantitative analysis.

RESULTS: ALS patients exhibited significantly reduced Low Frequency (LF) and High Frequency (HF) HRV parameters compared to healthy controls (p < 0.001 and p = 0.02, respectively). Time-domain parameters also showed significant reductions: RMSSD (p < 0.001), SDNN (p < 0.001), and pNN50% (p = 0.01). Despite an overall decrease in HRV, the LF/HF ratio did not show a statistically significant difference (p = 0.12).

CONCLUSION: Patients with ALS demonstrate autonomic dysfunction, evidenced by significant reductions in key time-domain (RMSSD, SDNN, pNN50%) and frequency-domain (LF, HF) parameters, suggesting impaired parasympathetic modulation. HRV may serve as a valuable, non-invasive biomarker for the early detection and management of cardiorespiratory complications in ALS.},
}

@article {pmid41666062,
year = {2026},
author = {Jin, J and Wang, H and Daly, I and Zhao, X and Li, S and Cichocki, A},
title = {A Fully Unsupervised Online Classification Algorithm for Event-Related Potential based Brain-Computer Interfaces.},
journal = {IEEE transactions on bio-medical engineering},
volume = {PP},
number = {},
pages = {},
doi = {10.1109/TBME.2026.3663323},
pmid = {41666062},
issn = {1558-2531},
abstract = {OBJECTIVE: Brain-computer interfaces (BCIs) based on event-related potentials (ERPs) are among the most accurate and reliable BCIs. However, current mainstream classification algorithms struggle to eliminate the need for calibration and rely on expensive labeled data, limiting the practical usability of ERP based BCIs. The development of fully unsupervised algorithms is essential for the advancement of practical applications of BCI systems.

METHODS: In this study, we propose a novel unsupervised classification method called sliding-window distribution distance maximization (sDDM). This algorithm utilizes sliding windows to highlight important temporal features and transforms the metric of inter-class differences from absolute distances to relative distribution distances in Mahalanobis space, while incorporating information on target event similarity from the BCI paradigm. Additionally, our proposed spatial dimensionality reduction strategy ensures smaller spatial dimensions and more prominent spatial features.

RESULTS: We compare our proposed method to other state of-the-art unsupervised classification methods and evaluate it offline on our self-collected dataset, a public dataset recorded during the use of a P300 Speller by patients with ALS, and the BCI Competition III Dataset II. Our results demonstrate that our proposed method achieves the best spelling accuracy across all datasets, surpassing other unsupervised algorithms. We further explore its improvement effectiveness through ablation experiments.

CONCLUSION: Our proposed method enhances the performance of unsupervised classification in ERP-based BCIs.},
}

@article {pmid41665722,
year = {2026},
author = {Peter, AS and Kandasamy, I and Ranjith, S and Jeyarajan, S and Chidambaram, P and Kumarasamy, A},
title = {Recombinant AMPs (Epinecidin-1 and its Variants): A New Hope against Invasive Fungal Infections against Candida spp. and Aspergillus flavus.},
journal = {Current microbiology},
volume = {83},
number = {4},
pages = {168},
pmid = {41665722},
issn = {1432-0991},
support = {311/RUSA(2.0)/2018//RUSA 2.0 Biological Sciences/ ; 01706/P6/2021//Tamil Nadu State Council for Higher Education/ ; IIRPSG-2024-01-01898, dt.11.02.2025//ICMR/ ; },
mesh = {*Antifungal Agents/pharmacology/chemistry ; *Aspergillus flavus/drug effects/physiology ; *Candida/drug effects/physiology/growth & development ; Microbial Sensitivity Tests ; Biofilms/drug effects/growth & development ; *Antimicrobial Peptides/pharmacology/genetics/chemistry ; Humans ; Recombinant Proteins/pharmacology/genetics ; Molecular Docking Simulation ; Hyphae/drug effects/growth & development ; *Antimicrobial Cationic Peptides/pharmacology/genetics ; },
abstract = {To enhance stability and antimicrobial efficacy of antimicrobial peptide (AMP) epinecidin-1, we previously engineered three variants - GK-epi-1, Variant-1 and Variant-2-by substituting alanine and histidine residues with lysine. Our current study focuses on the antifungal capabilities of Epinecidin-1 and its variants against the clinical isolates of Candida spp. (Candida albicans, C. tropicalis, C. krusei & C. glabrata) and Aspergillus flavus. Computational docking studies are evidenced, the peptides had strong affinity against all fungal receptor examined which indicates their efficacy to interact with the Candida cell membrane receptors (Exo-B-(1,3)-Glucanase, Secreted aspartic proteinase (SAP) 1 & N-terminal domain adhesin: Als 9 - 2). Minimum Inhibitory Concentration (MIC), Minimum Fungicidal Concentration (MFC) and antibiofilm assays revealed its potent antifungal activity, particularly in disrupting biofilm formation. Effects of peptides on hyphal growth inhibition activity and Scanning Electron Microscopy (SEM) confirmed that the mechanism of action involves pore formation, hyphal disruption and induction of reactive oxygen species in Candida cell membrane. The antifungal spectrum was extended to A. flavus, a known ocular pathogen, where combination therapy using sub-inhibitory concentrations of Epinecidin-1 and its variant peptides with Amphotericin B and Miconazole showed enhanced synergistic effects, reducing required dosages for effective pathogen control.},
}

*Antifungal Agents/pharmacology/chemistry
*Aspergillus flavus/drug effects/physiology
*Candida/drug effects/physiology/growth & development
Microbial Sensitivity Tests
Biofilms/drug effects/growth & development
*Antimicrobial Peptides/pharmacology/genetics/chemistry
Humans
Recombinant Proteins/pharmacology/genetics
Molecular Docking Simulation
Hyphae/drug effects/growth & development
*Antimicrobial Cationic Peptides/pharmacology/genetics

@article {pmid41665706,
year = {2026},
author = {Giacomini, PS and Voss, P and Devonshire, V and Schneider, R and Macaron, G and Hussein, S and Blanchette, F and de Villers-Sidani, É},
title = {Eye tracking as a digital biomarker in neurodegenerative diseases.},
journal = {Journal of neurology},
volume = {273},
number = {2},
pages = {133},
pmid = {41665706},
issn = {1432-1459},
mesh = {Humans ; *Neurodegenerative Diseases/diagnosis/physiopathology/complications ; Biomarkers ; *Eye-Tracking Technology ; *Eye Movements/physiology ; },
abstract = {Oculomotor abnormalities are a common finding in neurodegenerative diseases due to degeneration of neural pathways and brain regions involved in controlling eye movements. Pathological changes to the dorsolateral prefrontal cortex, basal ganglia, superior colliculus and cerebellum produce subtle changes in eye-movement metrics that may not be detected by clinical examination. The present review addresses the potential use of eye-movement biomarkers in neurodegenerative conditions such as multiple sclerosis, Parkinson's disease, Alzheimer's disease and other dementias, and amyotrophic lateral sclerosis. Eye-movement metrics such as saccades, anti-saccades, fixation and smooth pursuit are prognostic of disease progression, can differentiate pathologic subtypes as an aid to diagnosis, and enable clinicians to evaluate early worsening of motor and cognitive function. The cost of medical technologies limits their optimal use and accessibility in clinical practice. The shortage of subspecialist neurologists further limits access to care. New eye-tracking technologies incorporated into widely-accessible digital devices such as smart phones and tablets now permit detailed assessments with minimal equipment requirements, providing an important non-invasive and potentially cost-effective method for patient evaluation in routine clinical practice and as an aid to treatment decision-making. Digital biomarkers can be readily employed by healthcare professionals such as family physicians, nurses and pharmacists to bridge the care gaps, potentially providing them with powerful tools that can be broadly adopted to improve the delivery of care to patients with neurodegenerative conditions.},
}

Humans
*Neurodegenerative Diseases/diagnosis/physiopathology/complications
Biomarkers
*Eye-Tracking Technology
*Eye Movements/physiology

@article {pmid41665181,
year = {2026},
author = {Chiò, A and Calvo, A},
title = {Before Symptoms Begin: Immune Activation in Preclinical ALS.},
journal = {Annals of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ana.78174},
pmid = {41665181},
issn = {1531-8249},
}

@article {pmid41665049,
year = {2026},
author = {Grassano, M and Palumbo, F and Mora, G and Gallone, S and De Marco, G and Merulla, I and Paolantonio, C and Maccabeo, A and Canosa, A and Manera, U and Vasta, R and Iazzolino, B and Testa, M and Fuda, G and Salamone, P and Marchese, G and Casale, F and Moglia, C and Calvo, A and Borghero, G and Chiò, A},
title = {Sex-Specific Genetic Architecture of ALS: Evidence of a Female Protective Effect?.},
journal = {Annals of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ana.78172},
pmid = {41665049},
issn = {1531-8249},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) shows sex differences in incidence and age of onset, yet the underlying biological mechanisms remain poorly understood.

METHODS: We investigated sex-specific genetic architecture in an Italian ALS cohort with whole-genome sequencing (1,333 ALS cases, 755 controls). We performed a sex-stratified burden analysis of rare variants in ALS-associated genes and compared the proportions of male and female ALS patients carrying pathogenic or rare damaging variants. Key findings were replicated in the AnswerALS cohort (n = 723). Gene-specific sex ratios and familial history for C9ORF72, SOD1, and TARDBP were examined in an expanded dataset of 2,301 Italian ALS patients.

RESULTS: Sex-stratified burden testing revealed that rare variants in ALS genes were enriched in female cases versus controls (odds ratio [OR] 5.47, 95% confidence interval [CI] 1.60-34.29) but not in male cases. Female ALS patients more frequently carried rare damaging variants compared to males (23.2% vs 18.3%; OR 1.38, 95% CI 1.05-1.81), a finding that was replicated in the AnswerALS cohort (18.9% vs 12.4%; OR 1.58, 95% CI 1.10-2.26). Gene-level analyses of TARDBP carriers revealed a male predominance (2.1:1), yet a higher rate of familial history among females (40.4% vs 24.5%; OR 2.13, 95% CI 1.03-4.39).

INTERPRETATION: Females with ALS exhibited a higher overall burden of rare damaging variants, suggesting sex-related differences in genetic liability. Gene-level analyses indicate that the influence of sex varies across ALS genes, particularly TARDBP. These findings help explain epidemiological patterns and have implications for the identification of sex-linked protective mechanisms. ANN NEUROL 2026.},
}

@article {pmid41665027,
year = {2026},
author = {Huang, S and Bei, Y and Zhang, Q and Nan, H and Li, J},
title = {Behavioral Variant Frontotemporal Dementia With C9orf72 Intermediate Repeat Expansion: A case report.},
journal = {Alzheimer disease and associated disorders},
volume = {},
number = {},
pages = {},
doi = {10.1097/WAD.0000000000000718},
pmid = {41665027},
issn = {1546-4156},
abstract = {Hexanucleotide repeat expansion in the chromosome 9 open reading frame 72 (C9orf72) gene has been identified as the most common genetic cause of both frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). While large pathogenic expansions can reach hundreds to thousands of repeats, the lower limit for the number of pathogenic repeats remains controversial. Pathogenic threshold ranges from 30 to >60 repeats. Here, we report a rare case of behavioral variant frontotemporal dementia (bvFTD) associated with a C9orf72 repeat expansion of 49 units, a size that falls within the intermediate-length range. The patient presented with progressive neuropsychiatric decline, which progressed to include emotional blunting and memory impairment. Neuroimaging demonstrated bilateral temporal and hippocampal atrophy, with a reduction in glucose metabolism observed in the left fronto-parieto-temporal cortex and thalamus. This study may provide crucial clinical evidence for the ongoing debate on the pathogenicity of intermediate-length alleles in C9orf72.},
}

@article {pmid41664997,
year = {2026},
author = {Leykam, L and Forsberg, KME and Andersen, PM and Brännström, T and Weiner, S and Rönnholm, J and Blennow, K and Zetterberg, H and Marklund, SL and Gobom, J and Zetterström, P},
title = {N-Truncated Superoxide Dismutase-1 in Cerebrospinal Fluid Is Folded and Active.},
journal = {Journal of neurochemistry},
volume = {170},
number = {2},
pages = {e70382},
pmid = {41664997},
issn = {1471-4159},
support = {101053962//European Union's Horizon Europe research and innovation programme/ ; //Fort Knox Charity Foundation/ ; //Olsson och Olsson Foundation/ ; 2012-3167//Vetenskapsrådet/ ; 2017-00915//Vetenskapsrådet/ ; 2017-03100//Vetenskapsrådet/ ; 2019-02397//Vetenskapsrådet/ ; 2022-00732//Vetenskapsrådet/ ; 2022-01018//Vetenskapsrådet/ ; 2023-00356//Vetenskapsrådet/ ; 2012.0091//Knut och Alice Wallenbergs Stiftelse/ ; 2014.0305//Knut och Alice Wallenbergs Stiftelse/ ; 2020.0232//Knut och Alice Wallenbergs Stiftelse/ ; 2012-0262//Swedish Brain Foundation/ ; 2012-0305//Swedish Brain Foundation/ ; 2013-0279//Swedish Brain Foundation/ ; 2016-0303//Swedish Brain Foundation/ ; 2020-0353//Swedish Brain Foundation/ ; 2022-0270//Swedish Brain Foundation/ ; 2024-0048//Swedish Brain Foundation/ ; ALZ2022-0006//Swedish Brain Foundation/ ; //Västerbotten Läns Landsting/ ; //King Gustaf V:s and Queen Victoria's Freemason's Foundation/ ; //Ulla-Carin Lindquists stiftelse för ALS-forskning/ ; 2.1.12-1605-14//Neuroförbundet Association/ ; 2.1.6-452-20//Neuroförbundet Association/ ; 223-1881-13//Neuroförbundet Association/ ; 223-2808-12//Neuroförbundet Association/ ; //European Partnership on Metrology/ ; //Cure Alzheimer's Fund/ ; //Stiftelsen för Gamla Tjänarinnor/ ; //National Institute for Health and Care Research/ ; //University College London/ ; //UK Dementia Research Institute/ ; },
mesh = {*Superoxide Dismutase-1/cerebrospinal fluid/genetics/chemistry ; Humans ; Animals ; *Protein Folding ; Mice ; Amyotrophic Lateral Sclerosis/cerebrospinal fluid/genetics ; Male ; Female ; Mice, Transgenic ; *Superoxide Dismutase/cerebrospinal fluid/genetics ; },
abstract = {Mutations in the antioxidant enzyme superoxide dismutase-1 (SOD1) are a well-established cause of amyotrophic lateral sclerosis (ALS). The mutations promote SOD1 misfolding, resulting in protein aggregation and motor neuron degeneration. SOD1 is normally a structurally stable enzyme, and the mechanisms underlying SOD1 misfolding remain poorly understood. Approximately one third of SOD1 in cerebrospinal fluid (CSF) exhibits an N-terminal truncation, the biological significance of which remains unclear. This is remarkable given the dramatic effects ALS-linked C-terminal truncations have on the enzyme. In this study, we identified the truncation site and investigated its impact on SOD1 stability and enzymatic activity. Edman degradation revealed the cleavage site between Asn-26 and Gly-27, generating a 26-residue peptide that was confirmed by mass spectrometry. We analyzed postmortem tissues from different parts of the central nervous system (CNS), including the choroid plexus, and found only trace amounts of N-terminally truncated SOD1. Biochemical characterization of the SOD1 in CSF was done by size exclusion chromatography, ion exchange chromatography, and mass spectrometry. Our findings demonstrate that SOD1 in CSF retains full enzymatic activity, that the N-terminally truncated variant is mainly present in heterodimers with native SOD1 subunits, and that the dimer remains folded and active, with both fragments of the truncated SOD1 fixed after proteolysis. Truncated SOD1 was absent in human plasma. In mice, only transgenically expressed human SOD1 underwent truncation in CSF, whereas endogenous murine SOD1 remained intact. Lastly, the N-terminal truncation does not induce misfolding, unlike the destabilizing effects observed with C-terminal truncations. The location where the truncation takes place and the underlying mechanism could not be identified. Whether the N-truncated SOD1 variant contributes to ALS pathogenesis remains to be determined.},
}

*Superoxide Dismutase-1/cerebrospinal fluid/genetics/chemistry
Humans
Animals
*Protein Folding
Mice
Amyotrophic Lateral Sclerosis/cerebrospinal fluid/genetics
Male
Female
Mice, Transgenic
*Superoxide Dismutase/cerebrospinal fluid/genetics

@article {pmid41663779,
year = {2026},
author = {Roy, KK and Kumari, R and Upadhyay, AK and Mohanty, S},
title = {Tailoring treatments: pharmacogenomics in the management of neurodegenerative diseases.},
journal = {Acta neurologica Belgica},
volume = {},
number = {},
pages = {},
pmid = {41663779},
issn = {2240-2993},
abstract = {Neurodegenerative diseases like Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis are growing more common worldwide, yet treatment is still poor. Conventional therapies can have unforeseen side effects, produce poor medication reactions, and take longer to work. This persistent treatment gap highlights the need for novel approaches to these disorders' complex distinctions. Pharmacogenomics, which examines how genetic differences affect drug response, is a promising new subject and an urgent solution. Pharmacogenomics tailors medicine selection and administration to each patient's genetic profile, addressing the main causes of poor treatment response and preventable side effects. This research has enabled precision medicine that can improve neurodegenerative disease therapy and reduce harm. In this in-depth research, we examine neurodegenerative disease management issues, pharmacogenomics breakthroughs, and how incorporating genetics to clinical practice can improve outcomes. We examine the latest evidence that genetics affect drug breakdown, efficacy, and toxicity. We also discuss the challenges and opportunities of applying this knowledge. Pharmacogenomic approaches must be widely applied to make medicines for these awful disorders safer, more effective, and really suited to patient needs, according to our compilation.},
}

@article {pmid41663097,
year = {2026},
author = {Ritgen, J and Recker, F and Kolsch, M and Weichert, J and Degenhardt, J},
title = {The 'Falx Flash' sign as an indicator of accurate midsagittal plane alignment for fetal CNS and NT assessment in first trimester ultrasound.},
journal = {Ultraschall in der Medizin (Stuttgart, Germany : 1980)},
volume = {},
number = {},
pages = {},
doi = {10.1055/a-2808-0761},
pmid = {41663097},
issn = {1438-8782},
abstract = {PURPOSE: Obtaining a true mid-sagittal plane (MSP) and further Fetal Medicine Foundation (FMF) criteria is essential for accurate first-trimester ultrasound screening. The "Falx Flash" sign, a homogenous echo extending from the thalamus to the cranium, has been proposed as a useful appliance. This study investigates the association between the Falx Flash sign and additional key central nervous system structures.

MATERIAL AND METHODS: 
 We conducted a retrospective analysis of 185 first-trimester ultrasound examinations performed between 11+0 and 13+6 weeks' gestation. Images were reviewed for the presence of the Falx Flash sign and fulfillment of FMF criteria, including visualization of the nasal bone, brainstem, fourth ventricle, cisterna magna, thalamus delineation, and absence of zygomatic bone. Statistical comparisons between Falx Flash sign positive and negative groups were made using chi-square or Fisher's exact tests.

RESULTS: 
 The Falx Flash sign was present in 70% of cases. Its presence was strongly associated with improved visualization of midline structures: nasal bone (100% vs. 80%, p<0.0001), brainstem (97.7% vs. 76.4%, p<0.0001), fourth ventricle (96.2% vs. 72.7%, p<0.0001), cisterna magna (93.8% vs. 76.4%, p=0.0006), and thalamus delineation (98.5% vs. 49.1%, p<0.0001). Absence of the zygomatic bone was significantly more frequent with Falx Flash sign positive (76.2% vs. 16.4%, p<0.0001). There was no significant difference in fetal position, magnification, or caliper placement.

CONCLUSION: 
The Falx Flash sign is a reliable real-time marker of achieving a true MSP critical for correct NT measurement. Incorporating Falx Flash sign assessment into routine scanning protocols could improve anatomical visualization, enhance early anomaly detection, and reduce false-positive findings in first-trimester screening. Ziel: Bei dem Ersttrimesterscreening gemäß der Fetal Medicine Foundation ist die Gewinnung einer medianen Schnittebene essenziell. Das Falx Flash Zeichen entspricht dem Echo der Falx cerebri in der Medianebene und wurde als Marker für eine optimale Ebeneneinstellung vorgeschlagen. Die Studie untersucht den Zusammenhang zwischen dem Falx Flash Zeichen und weiterer wichtiger anatomischer ZNS Strukturen.

MATERIAL UND METHODEN: Es wurde eine retrospektive Analyse von 185 Ultraschalluntersuchungen (11+0 bis 13+6 SSW) durchgeführt. Die Bilder wurden hinsichtlich des Vorhandenseins des Falx Flash Zeichens und der Einhaltung der FMF-Kriterien bewertet: Die Darstellung von Nasenbein, Hirnstamm, viertem Ventrikel, Cisterna magna, Abgrenzung des Thalamus sowie das Fehlen des Jochbeins. Statistische Vergleiche zwischen Falx Flash Zeichen positiven und negativen Gruppen erfolgten mittels Chi-Quadrat- oder Fisher-Exakt-Test. Ergebnisse: Das Falx Flash Zeichen war in 70 % der Fälle nachweisbar. Dies war mit einer besseren Darstellung der Mittellinienstrukturen assoziiert: Nasenbein (100 % vs. 80 %), Hirnstamm (97,7 % vs. 76,4 %), vierter Ventrikel (96,2 % vs. 72,7 %), Cisterna magna (93,8 % vs. 76,4 %), Abgrenzung des Thalamus (98,5 % vs. 49,1 %) und Fehlen des Jochbeins (76,2 % vs. 16,4 %) war in der Falx-Flash-Gruppe signifikant häufiger. Es bestanden keine signifikanten Unterschiede hinsichtlich fetaler Position, Vergrößerung oder Platzierung der Messpunkte. Schlussfolgerungen: Das Falx Flash Zeichen ist ein Bestandteil der Medianebene und kann eine korrekte NT-Messung erleichtern. Die routinemäßige Beurteilung des Falx Flash Zeichen kann die anatomische Darstellung verbessern, die Früherkennung von Fehlbildungen fördern und die Rate falsch-positiver Befunde im Ersttrimesterscreening senken.},
}

@article {pmid41661214,
year = {2026},
author = {Miller, TM and Cudkowicz, ME and Shaw, PJ and Genge, A and Sobue, G and Bucelli, RC and Chiò, A and Van Damme, P and Ludolph, AC and Glass, JD and Andrews, JA and Babu, S and Benatar, M and McDermott, CJ and Salachas, F and Bruneteau, G and Al-Chalabi, A and Amorin, M and Nestorov, I and Graham, D and Lin, L and Sun, P and McNeill, M and Malek, S and Inra, J and Garafalo, S and Fradette, S and , },
title = {Long-Term Tofersen in SOD1 Amyotrophic Lateral Sclerosis.},
journal = {JAMA neurology},
volume = {83},
number = {2},
pages = {115-125},
pmid = {41661214},
issn = {2168-6157},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics ; Male ; Middle Aged ; Female ; Double-Blind Method ; *Superoxide Dismutase-1/genetics ; Aged ; Adult ; *Oligonucleotides/therapeutic use/administration & dosage ; *Oligonucleotides, Antisense/therapeutic use ; Treatment Outcome ; },
abstract = {IMPORTANCE: Approximately 2% of amyotrophic lateral sclerosis (ALS) cases are attributable to a pathogenic variant in the superoxide dismutase 1 (SOD1) gene. Tofersen, an intrathecal antisense oligonucleotide designed to reduce SOD1 protein synthesis, is the first and only approved therapy for the treatment of ALS in adults who have a variant in the SOD1 gene.

OBJECTIVE: To evaluate the long-term effects of tofersen in adults with SOD1-ALS.

The phase 3, randomized, double-blind, placebo-controlled VALOR trial (A Study to Evaluate Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Tofersen in SOD1-ALS; conducted from March 2019 to July 2021) evaluated tofersen use over 28 weeks in adults (18 years and older) with weaknesses attributable to ALS and a confirmed SOD1 pathogenic variant at 32 sites in 10 countries; participants could then enroll in an open-label extension (OLE; completed August 2024).

INTERVENTION AND EXPOSURE: Adults with SOD1-ALS were randomly assigned 2:1 to receive tofersen (100 mg) or placebo over a 24-week period in the VALOR study. All participants in the OLE were treated with tofersen.

MAIN OUTCOMES AND MEASURES: Integrated analysis of VALOR and the OLE study aimed to compare early start vs placebo/delayed start (approximately 6 months later) treatment with tofersen. Key efficacy end points included measures of axonal injury and neurodegeneration (neurofilament), function and strength, quality of life, and survival.

RESULTS: VALOR enrolled 108 participants with 42 unique SOD1 pathogenic variants (mean [SD] age: placebo/delayed-start group 51.2 [11.6] [n = 36]; early-start group: 48.1 [12.6] [n = 72]) with 19 (53%) and 43 (60%) of participants being male in the placebo/delayed- and early-start groups, respectively. Overall, 95/108 participants (88%) enrolled in the OLE, and 46 participants completed the OLE (early-start group, 34 [47%]; placebo/delayed-start group, 12 [33%]). At OLE completion, participants could have accumulated 3.5 years or more (range, 192-276 weeks) of follow-up from the start of VALOR. Over 148 weeks, earlier initiation of tofersen (compared to later initiation) was associated with numerically less decline in measures of clinical function (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised score, -9.9 vs -13.5 points), respiratory function (slow vital capacity, -13.8% vs -18.1%), muscle strength (handheld dynamometry megascore, -0.38 vs -0.43 points), and quality of life (Amyotrophic Lateral Sclerosis Assessment Questionnaire 5 score, 17.0 vs 22.5 points; EuroQol 5 Dimension, 5 Level Questionnaire score, -0.1 vs -0.2 points). Tofersen prolonged survival relative to the expected natural history of SOD1-ALS. Most adverse events were consistent with ALS progression or known procedural adverse effects. All serious neurological adverse events were reversible; few led to tofersen discontinuation.

CONCLUSIONS AND RELEVANCE: Final data from VALOR and the OLE demonstrated the benefit of tofersen in SOD1-ALS and provide clear rationale for its use in this population.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: VALOR NCT02623699; OLE NCT03070119.},
}

Humans
*Amyotrophic Lateral Sclerosis/drug therapy/genetics
Male
Middle Aged
Female
Double-Blind Method
*Superoxide Dismutase-1/genetics
Aged
Adult
*Oligonucleotides/therapeutic use/administration & dosage
*Oligonucleotides, Antisense/therapeutic use
Treatment Outcome

@article {pmid41661136,
year = {2026},
author = {Liu, X and Wang, J and Zhan, J and Wang, Q and Lin, X and Li, H and Li, H},
title = {Dual-Field Amplification via Nanotip-Engineered Catalysts for Efficient Spin-State and Ion Regulation in Aluminum-Sulfur Batteries.},
journal = {ACS nano},
volume = {},
number = {},
pages = {},
doi = {10.1021/acsnano.5c16319},
pmid = {41661136},
issn = {1936-086X},
abstract = {Modulating the electronic structure of catalysts through external magnetic fields is a promising strategy for enhancing electrocatalytic activity, which has been successfully demonstrated in the oxygen evolution reaction (OER), zinc-air batteries and lithium-sulfur batteries. However, conventional magnetic regulation approaches typically focus solely on spin-state modulation, neglecting the ion transport limitations in practical systems. Additionally, existing permanent magnets and ferromagnetic additives generate magnetic fields with limited intensity and nonuniform directionality, restricting their effectiveness. Herein, we propose a tip-enhanced magnetic-electric dual-field strategy by rationally designing ferromagnetic NiCo2O4 catalysts with nanotip architectures to address long-standing kinetic bottlenecks in aluminum-sulfur (Al-S) batteries. Finite element analysis demonstrates that the high-curvature tips significantly amplify local electric and magnetic fields by approximately 4.2- and 2.6-fold, respectively, under an external field. Moreover, the induced spin-state transition of Ni[3+] to high-spin (HS) states enhances d-p orbital hybridization with polysulfide intermediates, effectively lowering reaction barriers. This dual enhancement synergistically promotes ion transport via magnetohydrodynamic (MHD) effects, leading to substantially reduced voltage hysteresis and markedly improved electrochemical performance, delivering a high reversible capacity of 513 mAh g[-1] after 700 cycles in Al-S batteries. By integrating geometric field amplification with spin-state modulation, this work presents a highly efficient and scalable strategy for approach to designing high-performance catalysts for advanced Al-S batteries.},
}

@article {pmid41661021,
year = {2026},
author = {Pervushina, EV and Kutlubaev, MA and Kuznetsova, DR and Karimova, GI and Kachemaeva, OV and Mkhitaryan, EA},
title = {[Combination of amyotrophic lateral sclerosis with Alzheimer's disease].},
journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova},
volume = {126},
number = {1},
pages = {132-136},
doi = {10.17116/jnevro2026126011132},
pmid = {41661021},
issn = {1997-7298},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/diagnosis ; *Alzheimer Disease/complications/diagnosis ; Male ; Aged ; Female ; Middle Aged ; },
abstract = {The combination of amyotrophic lateral sclerosis (ALS) with Alzheimer's disease is rare. Currently, it is unclear whether such comorbidity is an accidental coincidence or a manifestation of a specific pathological process. A case of simultaneous occurrence of classic symptoms of the bulbar form of ALS and Alzheimer's disease is presented. The possible mechanisms of the combination of two diseases are analyzed.},
}

Humans
*Amyotrophic Lateral Sclerosis/complications/diagnosis
*Alzheimer Disease/complications/diagnosis
Male
Aged
Female
Middle Aged

@article {pmid41660682,
year = {2026},
author = {Li, J and Zhu, D and Yang, W and Guan, T and Yang, L and Gong, W and Liu, X and You, J and Feng, J and Chen, X},
title = {Lifestyle-Associated Metabolic Signature Predicts the Risk of Amyotrophic Lateral Sclerosis.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70166},
pmid = {41660682},
issn = {1097-4598},
support = {24Y12800900//Shanghai Science and Technology Commission 2024 Science and Technology Innovation Action Plan Medical Innovation research field project/ ; 82371431//National Natural Science Foundation project/ ; },
abstract = {INTRODUCTION/AIMS: Although the association between certain lifestyle factors and the risk of amyotrophic lateral sclerosis (ALS) has been recognized, the potential mechanism underlying it remains unexplored. This study aimed to identify the metabolic signature indicative of lifestyle factors related to ALS, to examine its association with ALS risk, and to evaluate the mediating effects of muscle strength underlying these associations.

METHODS: This study used UK Biobank data, including ALS diagnoses, potential ALS-related factors, metabolomics, and hand grip strength. A total protective factor score was calculated from lifestyle data. Multivariable Cox regression analyzed associations between the score, its components, and ALS risk. ALS-related metabolic signatures were identified via elastic net regression. ALS risk across signature levels was compared by log-rank tests. Mediation analysis assessed the role of baseline hand grip strength.

RESULTS: 248,222 participants were included in this study. Among lifestyle factors, the total protective factor score, no military service, and higher body mass index were significantly associated with reduced ALS risk. The metabolic signature derived from 163 metabolites indicative of potential ALS-associated protective factors was identified and found to be associated with lower ALS risk. Baseline hand grip strength of both hands was also associated with reduced ALS risk. Mediation analysis revealed that right-hand grip strength significantly mediated the associations between the total protective factor score, the metabolic signature, and ALS risk.

DISCUSSION: Our study highlights the potential of the metabolic signature as a biomarker for early disease identification and underscores the importance of lifestyle-based prevention strategies.},
}

@article {pmid41659894,
year = {2026},
author = {Boucher Grenon, J and Doyon, C and Laliberté, T and Campeau-Lecours, A},
title = {Design of a low-cost mechanical 3D-Printed hand orthosis for grasping assistance in activities of daily living.},
journal = {Journal of rehabilitation and assistive technologies engineering},
volume = {13},
number = {},
pages = {20556683261422642},
pmid = {41659894},
issn = {2055-6683},
abstract = {The ability to grasp objects has a significant impact on the independence of individuals following a stroke, a spinal cord injury, or for those who are living with amyotrophic lateral sclerosis. In most cases, physical rehabilitation is not sufficient to regain the hand function necessary for day-to-day life. Hand orthoses capable of providing grasping assistance in activities of daily living are therefore crucial to a more independent lifestyle. However, most available options struggle to offer an acceptable balance between cost, size, weight and functionality, resulting in limited use in practice. This article presents a low-cost, 3D-printed hand orthosis that relies solely on mechanical elements to aid in finger flexion. An underactuated, flexible design for the fingers with nylon strips as spring blades was used to achieve a design that costs only 27% of the price of comparable commercially available options, as well as being very lightweight and easily customizable. It was also demonstrated that rigid thumb supports allowed the orthosis to be used in the majority of daily grasping tasks. Finally, the use of the proposed mechanism was shown to be able to provide up to 4 N of flexion assistance to the finger when using a medium wrap grip.},
}

@article {pmid41658940,
year = {2026},
author = {Farinazzo, G and Giagnorio, E and Marcuzzo, M and Cattaneo, M and Malacarne, C and Cavalcante, P and Bonanno, S and Maderna, E and Pensato, V and Gellera, C and Marucci, G and Mazzetti, S and Salvi, E and Lauria, G and Marcuzzo, S},
title = {MicroRNA profiling in post-mortem spinal cord of C9ORF72-related ALS patients reveals molecular pathways involved in motor neuron degeneration.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1741065},
pmid = {41658940},
issn = {1662-4548},
abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder causing progressive motor neuron death in cortex, brainstem and spinal cord. The most common genetic cause is the G4C2 hexanucleotide repeat expansion in the non-coding region of exon 1 of C9ORF72, accounting for ~40% of familial and ~7% of sporadic ALS. RNA dysregulation is increasingly recognized as a key contributor to ALS pathogenesis. This study aimed to identify specific microRNAs (miRNAs) involved in motor neuron degeneration in C9ORF72-ALS.

METHODS: We profiled 754 miRNAs in human post-mortem spinal cord tissue from C9ORF72-ALS patients and healthy donors. Laser capture microdissection isolated ventral horn regions, and in silico target prediction identified potential genes and pathways regulated by differentially expressed miRNAs. Target genes were validated by Real time PCR.

RESULTS: Two subsets of miRNAs were exclusively expressed in ventral horn regions: miR-200b-3p and miR-346 in C9ORF72-ALS patients, and miR-30d-5p, miR-106b-5p and miR-135a-5p in healthy donors. Target prediction and molecular analysis identified putative genes and pathways linked to cell death, inflammation, protein metabolism, DNA modification, excitotoxicity, autophagy and vesicles trafficking.

DISCUSSION: This study identifies specific miRNAs and their target genes as key molecules in motor neuron degeneration in C9ORF72-ALS. Restoring their expression could represent a therapeutic approach for ALS.},
}

@article {pmid41658391,
year = {2026},
author = {Kanj, G and Malaeb, D and Sakr, F and Dabbous, M and Obeid, S and Hallit, S and Fekih-Romdhane, F},
title = {Psychometric properties of an Arabic translation of the short form of the affective lability scale in a sample of Lebanese adults.},
journal = {Frontiers in psychology},
volume = {17},
number = {},
pages = {1642617},
pmid = {41658391},
issn = {1664-1078},
abstract = {BACKGROUND: The present study aimed to investigate the psychometric properties of an Arabic version of the Affective Lability Scale in its short form (ALS-18) within an Arabic-speaking sample. Particularly, the concurrent validity, sex invariance and factorial structure were examined.

METHODS: The total sample of this cross-sectional study consisted of 748 adults, with a mean age of 34.48 ± 13.25 years, 66.5% females. After completing the forward-backward translation for cultural and linguistic adaptation, concurrent validity was assessed through correlations with related constructs, Confirmatory Factor Analysis was conducted to examine the factorial structure, and internal reliability as well as measurement invariance across sex were tested, the latter being through multigroup analyses.

RESULTS: The fit of the scale's original three-factor model was suggested through confirmatory factor analyses. Full measurement invariance at the configural, metric, and scalar levels was attained. The scale also yielded concurrent validity, with results indicating associations with increased levels of depression, anxiety and stress, and lower levels of self-esteem. The study's findings further denoted good internal consistency of the Arabic ALS-18 with values of McDonald's ω and Cronbach's α greater than 0.70.

CONCLUSION: Results revealed that the Arabic ALS-18 is a reliable and valid self-report measure that could be utilized among an Arabic-speaking population to assess affective lability. The availability of the Arabic version of the ALS-18 is deemed to increase its use for research and provide a foundation for future clinical validation studies, globally benefiting Arabic-speaking individuals.},
}

@article {pmid41657419,
year = {2026},
author = {Wang, Z and Huang, J and Yun, D},
title = {Current and emerging therapeutic strategies for amyotrophic lateral sclerosis: from pharmacological approaches to gene and stem cell therapies.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1729302},
pmid = {41657419},
issn = {1664-2295},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that involves upper and lower motor neurons, severely impairing patients' quality of life. The complex interaction of genetic and environmental factors in ALS pathophysiology complicates therapeutic development. Currently available disease-modifying pharmacological therapies for ALS offer limited efficacy, only slowing disease progression to a modest degree. The recent market withdrawal of a previously approved therapy (AMX0035) further underscores the challenges in this field. Biological targets for ALS and related neurodegenerative diseases offer a unique avenue for therapeutic intervention. With the advancement of genetic engineering technology, innovative therapies such as Stem cell therapy and gene therapy are also discussed, offering a promising horizon for ALS treatment. In addition, the management of ALS symptoms plays a key role in improving the daily lives of people with the disease. In this review, we summarize various strategies for treating ALS, providing an overview of the disease.},
}

@article {pmid41656808,
year = {2025},
author = {Yu, C and Zeng, W and Meekrathok, P and Bu, Y and Wang, J and Qiu, J},
title = {[Heterogeneity in the regulation of cellular stress responses by FUS gene mutations associated with amyotrophic lateral sclerosis].},
journal = {Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences},
volume = {50},
number = {10},
pages = {1755-1770},
doi = {10.11817/j.issn.1672-7347.2025.250211},
pmid = {41656808},
issn = {1672-7347},
support = {2019RS1010//the Project of Department of Science and Technology of Hunan Province/ ; },
mesh = {*RNA-Binding Protein FUS/genetics/chemistry ; Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Mutation ; Nuclear Localization Signals/genetics ; Reactive Oxygen Species/metabolism ; *Stress, Physiological/genetics ; },
abstract = {OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the selective death of motor neurons, exhibiting marked clinical heterogeneity and lacking effective treatment. The etiology and pathogenic mechanisms remain incompletely understood. The FUS (fused in sarcoma) gene is one of the key causative genes in ALS. Pathogenic mutations in the encoded protein are predominantly clustered in the C-terminal nuclear localization signal (NLS) region, and distinct NLS mutation sites show considerable differences in pathogenic potency, clinical phenotypes, and molecular mechanisms. This study focuses on 2 representative pathogenic NLS mutations of FUS (FUS[R514S] and FUS[P525L]) to investigate their differential regulation of cellular stress responses and explore the underlying mechanisms.

METHODS: Multiple sequence alignment of FUS protein homologs from 12 species was performed using an online tool from the National Center for Biotechnology Information (NCBI) to determine the evolutionary conservation of residues R514 and P525. The three-dimensional (3D) structure of the nuclear transport receptor-FUS complex [Protein Data Bank (PDB) ID: 5YVG] was analyzed and visualized using PyMOL. Structure of FUS mutants were generated using the mutation wizard tool in PyMOL by selecting the target conformational isomer and executing the mutation workflow. Tet-on inducible expression cell models for FUS wild-type (WT) and mutant FUS (FUS[R514SS] and FUS[P525L]) were established in human embryonic kidney 293T (HEK293T) cells. Protein expression levels and subcellular localization of FUS were assessed by Western blotting and immunofluorescence assay, respectively. FUS aggregation states were compared between WT and mutant FUS using a digitonin-based permeabilization and extraction assay, followed by sodium dodecylsulfate-polyacrylamide gel electrophoresis-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting analysis. Blue native PAGE (BN-PAGE) was used to evaluate the stability of FUS-containing complexes. Mitochondrial membrane potential and reactive oxygen species (ROS) levels were measured by flow cytometry. Stress granule (SG) formation was induced using sodium arsenite, and the effects of WT and mutant FUS on SG dynamics were analyzed by immunofluorescence assay. Protein expression changes of mitochondrial function-related proteins [translocase of outer membrane 20 kD subunit (Tom20) and voltage-dependent anion channel 1 (VDAC1)] and key molecules of the integrated stress response (ISR) pathway [phosphorylated-eukaryotic initiation factor 2 alpha (p-eIF2α) and activating transcription factor 4 (ATF4)] were examined by Western blotting.

RESULTS: Sequence alignment revealed that R514 and P525 are highly conserved across FUS homologs from 12 species. Structural analysis indicated that the FUS[R514S] and FUS[P525L] mutations disrupt hydrogen bonding or hydrophobic interactions between FUS and importin-β2, weakening the stability of these interactions. Western blotting confirmed the successful establishment of inducible WT and mutant FUS expression cell models, and exogenous FUS expression slightly suppressed endogenous FUS protein levels. Immunofluorescence assay demonstrated that WT FUS is predominantly localized in the nucleus, whereas both FUS[R514S] and FUS[P525L] mutants mislocalize to the cytoplasm with a punctate, granular distribution. Compared with WT FUS, neither mutant significantly affected mitochondrial membrane potential, ROS levels, or the homeostasis of mitochondrial function-related proteins (all P>0.05). Upon sodium arsenite exposure, mutant FUS formed SGs more rapidly, generated SGs with larger diameters, and displayed distinct intracellular distribution and aggregation patterns relative to WT (P>0.05). After drug withdrawal, WT and mutant FUS showed no significant difference in their effects on SG disassembly (P<0.05). Under basal conditions, FUS[R514S] exhibited significantly higher eIF2α phosphorylation levels than WT, and ATF4 protein levels also showed an increasing trend (P<0.05). No statistically significant difference was observed between FUS[P525L] and WT FUS in these measures (P>0.05). Sodium arsenite treatment increased eIF2α phosphorylation across all groups, eliminating inter-mutant differences.

CONCLUSIONS: Distinct pathogenic NLS mutations of FUS differentially regulate cellular stress responses through different mechanisms, contributing to ALS initiation and progression. Among these, FUS[P525L] promotes the formation of larger stress granules, whereas FUS[R514S] more readily activates the cellular ISR.},
}

*RNA-Binding Protein FUS/genetics/chemistry
Humans
*Amyotrophic Lateral Sclerosis/genetics
*Mutation
Nuclear Localization Signals/genetics
Reactive Oxygen Species/metabolism
*Stress, Physiological/genetics

@article {pmid41655843,
year = {2026},
author = {Mulla, Z and Coupe, N},
title = {Halal and Healthy: A Qualitative Study of British Muslim Perspectives on Meat Consumption and Plant-based Diets.},
journal = {Appetite},
volume = {},
number = {},
pages = {108496},
doi = {10.1016/j.appet.2026.108496},
pmid = {41655843},
issn = {1095-8304},
abstract = {Reducing meat consumption has the potential to improve both population and planetary health, however approaches to this have not been fully explored, particularly in the British Muslim community. British Muslims consume more meat than the average British person and face disproportionate diet related health risks. Although reducing meat consumption and eating more plant-based is known to reduce such health risks, there is limited understanding of British Muslim perceptions of this dietary transition. This study explored the barriers and facilitators towards British Muslims reducing meat consumption by increasing consumption of plant-based foods. The qualitative study involved semi-structured interviews with 15 British Muslims from Greater Manchester. Interviews were inductively analysed using reflexive thematic analysis and then deductively mapped to Michie et al.'s (2014) COM-B model. Two themes were identified. "Islamic Teachings and Food Choices" highlighted how Islamic teachings and practices gave religious significance to meat and taught foundational ethics that could encourage plant-based diets identified as reflective motivation influences. "The Value of Meat" explored perceptions of the elevated status of meat, influenced by beliefs about health, socio-economic status, and sociocultural norms. Social opportunity and reflective motivation were key influences identified in this theme. This study emphasised the importance of culturally relevant dietary interventions considering religious beliefs and community norms.},
}

@article {pmid41655130,
year = {2026},
author = {Xiang, Q and Liu, Y and Wang, J},
title = {Golgi fragmentation driven by the USP11-ITCH axis triggers autolysosomal failure in neurodegeneration.},
journal = {Autophagy},
volume = {},
number = {},
pages = {},
doi = {10.1080/15548627.2026.2629295},
pmid = {41655130},
issn = {1554-8635},
abstract = {Golgi fragmentation is a prominent early hallmark of neurodegenerative diseases such as Alzheimer disease (AD) and amyotrophic lateral sclerosis (ALS), yet the shared molecular mechanisms underlying this phenomenon remain poorly understood. Here we identify the E3 ubiquitin ligase ITCH as a central regulator of Golgi integrity and proteostasis. Elevated ITCH disrupts both cis- and trans-Golgi networks, dislocates lysosomal hydrolase sorting factors, and impairs maturation of hydrolases. The ensuing lysosomal dysfunction leads to autophagosome accumulation and defective clearance of accumulated cytoplasmic toxic proteins like TARDBP/TDP-43. Genetic and pharmacological inhibition of ITCH restores autolysosomal degradation and protects neurons in both mammalian and Drosophila models. Aberrant buildup of the deubiquitinase USP11 drives ITCH accumulation, intensifying neuronal proteotoxic stress in individuals with AD and ALS. These findings reveal a mechanistic pathway connecting Golgi disorganization, autolysosomal impairment, and proteotoxic stress in neurodegeneration.},
}

@article {pmid41654110,
year = {2026},
author = {Shen, Y and Shen, S and Luo, ZG},
title = {Gene-targeted versus broad-spectrum therapies in ALS: comparative lessons and strategic outlook.},
journal = {Journal of genetics and genomics = Yi chuan xue bao},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jgg.2026.01.012},
pmid = {41654110},
issn = {1673-8527},
abstract = {Amyotrophic lateral sclerosis (ALS) is a relentless and fatal neurodegenerative disorder characterized by the progressive loss of motor neurons, leading to muscle weakness, paralysis, and ultimately, respiratory failure. Despite a growing understanding of its complex pathophysiology, therapeutic options remain limited. This review critically analyzes recent clinical advances by comparing two divergent strategies, including precision gene-targeted therapies for monogenic ALS subtypes and broad-spectrum agents for the wider sporadic population. While gene therapies like tofersen demonstrate clear molecular target engagement, their translation to robust clinical benefit remains a challenge. In contrast, broad-spectrum agents have faced consistent late-stage failures, often due to the disease's underlying diversity, which undermines a one-size-fits-all approach. We argue that this heterogeneity, coupled with a lack of predictive biomarkers and the difficulty of late-stage intervention, represents the core barrier to progress. The future of ALS therapeutics therefore depends on a strategic pivot toward personalized medicine. This requires prospectively stratifying patients, developing rational combination therapies, and intervening earlier in the disease course, ultimately treating ALS as a syndrome of distinct molecular diseases rather than a single entity.},
}

@article {pmid41654003,
year = {2026},
author = {Sia, T and Sheehy, TP and Morgan, P and Wools, CA and Zhao, Y and Gibbs, R and Mathieson, S and Smith, AA},
title = {Trajectory of Mobility Fuction Decline for People with Motor Neuron Disease.},
journal = {Archives of physical medicine and rehabilitation},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.apmr.2026.01.028},
pmid = {41654003},
issn = {1532-821X},
abstract = {OBJECTIVE: The primary aim of this study was to explore factors that may influence the rate of mobility function decline. A secondary aim was to identify the impact of neck weakness on mobility decline in people living with motor neuron disease (MND).

DESIGN: Retrospective, longitudinal observational study design.

SETTING: This study was undertaken at a State-wide Progressive Neurological Disease Service (SPNDS) in the inpatients, outpatients and community-based services. The SPNDS clinic treats adults with MND from both metropolitan and rural settings.

PARTICIPANTS: Adults with motor neuron disease attending the Statewide Progressive Neurological Disease Service were recruited to participate in the study.

INTERVENTIONS: Not applicable.

MAIN OUTCOME MEASURES: categorical data relating to mobility function (walking endurance, gait aid used and level of assistance required) was recorded. Neck weakness was measured as present or absent based on participant subjective report and/or objective observation of head position when upright.

RESULTS: Results from the 358 participants recruited showed that the median time to loss of independent gait was 30.5 months (range 4-239; IQR 26), full time wheelchair use was 34 months (IQR 35; range 5-238) and median time to becoming housebound was 28 months from MND symptom onset (IQR 24.5; range 5-219 months). 141 (39.4%) participants had neck weakness. The presence of neck weakness resulted in earlier loss of independent gait and quicker to become housebound. There was no significant difference in time to full time wheelchair use between participants with or without neck weakness.

CONCLUSION: There was an effect of both phenotype and neck weakness on the trajectory of mobility function decline in people with MND. Overall, people with amyotrophic lateral sclerosis (ALS) phenotype (bulbar, cervical or lumbar onset) experienced a more rapid rate of decline in mobility function than those with flail limb and primary lateral sclerosis (PLS) phenotypes. Additionally, those demonstrating neck weakness were quicker to decline in mobility than those without neck weakness.},
}

@article {pmid41653702,
year = {2026},
author = {Sebastianelli, L and Versace, V and Ferrazzoli, D and Ortelli, P and Trinka, E and Sellner, J and Nardone, R},
title = {Neurophysiology in the mirror: A tri-layer model of mirror movements informed by TMS evidence.},
journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology},
volume = {184},
number = {},
pages = {2111692},
doi = {10.1016/j.clinph.2026.2111692},
pmid = {41653702},
issn = {1872-8952},
abstract = {OBJECTIVE: Mirror movements are involuntary, task-coupled contractions in contralateral homologous muscles during unilateral movement. While often described as a developmental remnant or rare clinical sign, mirror movements offer insight into the physiological mechanisms that underlie motor lateralization and interhemispheric balance. This review aimed to synthesize the available neurophysiological evidence-primarily from transcranial magnetic stimulation (TMS)-and propose a structured, mechanism-based framework for interpreting mirror movements across neurological conditions.

METHODS: A structured narrative review was conducted of studies published between 1966 and November 2025 using TMS in individuals with congenital, developmental, or acquired mirror movements. Studies using neuroimaging or peripheral electrophysiology were included selectively to support anatomical or functional interpretation of TMS findings. Data were organized into three mechanistic layers based on prevailing neurophysiological signatures rather than etiology alone.

RESULTS: Three non-mutually exclusive mechanisms were identified: (I) persistent fast-conducting ipsilateral corticospinal projections, primarily in congenital mirror movement syndromes and early brain injury; (II) deficient transcallosal inhibition, observed in conditions affecting interhemispheric balance such as amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, and callosal agenesis; and (III) bilateral overactivation of premotor and supplementary motor areas, especially under conditions of impaired motor program selection or increased task demands.

CONCLUSIONS: Mirror movements can be interpreted within a tri-layer model reflecting distinct disruptions in corticospinal connectivity, interhemispheric inhibition, and supraspinal motor control.

SIGNIFICANCE: This framework provides an integrative model for interpreting neurophysiological findings in mirror movements, offering insight into hierarchical motor control without implying specific diagnostic or therapeutic applications.},
}

@article {pmid41653524,
year = {2026},
author = {Kim, SH and Roh, YS},
title = {Effects of a theory-based advanced life support booster training program on competency retention in nursing students: A randomized controlled trial.},
journal = {Nurse education in practice},
volume = {92},
number = {},
pages = {104754},
doi = {10.1016/j.nepr.2026.104754},
pmid = {41653524},
issn = {1873-5223},
abstract = {AIM: This study evaluated the effectiveness of a theory-based advanced life support (ALS) booster training program on six-month retention of knowledge, skills performance and teamwork.

BACKGROUND: Retention of ALS competencies is vital for nursing students, yet skills and knowledge often decline within months of initial training.

DESIGN: A randomized controlled trial was conducted.

METHODS: A convenience sample of 65 fourth-year nursing students were randomly assigned to an experimental group (n = 33) receiving a two-hour booster session based on mastery learning and deliberate practice theories or to a control group (n = 32). ALS knowledge, skills and teamwork were measured at baseline and six months post-training. Data were analyzed using non-parametric tests and generalized estimating equation.

RESULTS: Both groups experienced declines over time. However, the experimental group showed significantly better retention in skills performance (p < .001) and teamwork (p = .025). Knowledge retention was higher but not statistically significant (p = .116).

CONCLUSIONS: A brief, theory-based booster session effectively improved long-term retention of ALS skills and teamwork, supporting its integration into nursing education.},
}

@article {pmid41653014,
year = {2026},
author = {Abrahao, A and Ciepielewska, M and Zinman, L},
title = {Value of Clinical Evidence and Health Economics and Outcomes Research (HEOR) Studies.},
journal = {Muscle & nerve},
volume = {73 Suppl 1},
number = {Suppl 1},
pages = {S7-S12},
pmid = {41653014},
issn = {1097-4598},
support = {//Mitsubishi Tanabe Pharma America, Inc./ ; },
mesh = {Humans ; *Outcome Assessment, Health Care/economics ; *Economics, Medical ; Randomized Controlled Trials as Topic ; Amyotrophic Lateral Sclerosis/therapy/economics ; *Evidence-Based Medicine/economics ; Cost-Benefit Analysis ; },
abstract = {Randomized controlled trials (RCTs) remain the gold standard for establishing the efficacy and safety of new treatments. However, clinical evidence derived from the systematic analysis of real-world data generated through routine clinical practice can complement RCT data by offering insights into treatment performance in broader, more heterogeneous patient populations and clinical care settings. The integration of high-quality clinical evidence into health economics and outcomes research (HEOR) is increasingly important, as it supports healthcare decision-making across multiple stakeholders, including regulatory agencies, payers, clinicians, and patients. Multiple study designs, such as pragmatic trials, hybrid RCTs, external control arms, and observational studies, can provide valuable clinical evidence beyond the controlled trial setting. These data can enhance understanding of comparative effectiveness, patient-reported outcomes, treatment safety, and healthcare utilization and costs. The field of amyotrophic lateral sclerosis offers a compelling example of how clinical evidence derived from global registries and clinical studies has advanced understanding of disease epidemiology, treatment patterns, and the effectiveness of therapies, including riluzole and edaravone. Consequently, this review and the associated supplementary articles are meant to serve as a primer to inform clinicians of the potential contribution of clinical evidence to HEOR studies.},
}

Humans
*Outcome Assessment, Health Care/economics
*Economics, Medical
Randomized Controlled Trials as Topic
Amyotrophic Lateral Sclerosis/therapy/economics
*Evidence-Based Medicine/economics
Cost-Benefit Analysis

@article {pmid41653010,
year = {2026},
author = {Abrahao, A and Zinman, L and Apple, S},
title = {Current and Ongoing Clinical Studies.},
journal = {Muscle & nerve},
volume = {73 Suppl 1},
number = {Suppl 1},
pages = {S26-S28},
pmid = {41653010},
issn = {1097-4598},
support = {//Mitsubishi Tanabe Pharma America, Inc./ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Edaravone/therapeutic use ; *Clinical Trials as Topic ; *Free Radical Scavengers/therapeutic use/administration & dosage ; },
abstract = {This article provides a comprehensive overview of current and ongoing studies evaluating intravenous (IV) edaravone and edaravone oral suspension in the treatment of amyotrophic lateral sclerosis (ALS). In addition to data from clinical practice and post hoc analyses, multiple observational and interventional studies are underway to better understand the efficacy, safety, and biological impact of edaravone in clinical settings. Key studies include SUNRISE Japan, a long-term postmarketing surveillance study of IV edaravone in Japanese patients with ALS; the ALS/Motor Neuron Disease Natural History Study, a longitudinal registry designed to inform clinical trial design and track ALS progression; and the REFINE-ALS study, which is actively collecting biomarker data to elucidate the pathophysiologic mechanisms influenced by edaravone. For edaravone oral suspension, United States Food and Drug Administration approval was supported by Study MT-1186-A01, a phase 3 trial assessing safety and tolerability over 48 weeks, with extension Study MT-1186-A03. Study MT-1186-A02, conducted as an FDA postmarketing commitment, and its extension, Study MT-1186-A04, evaluated whether investigational once daily dosing showed superior efficacy vs. the approved on/off dosing regimen. Collectively, these studies contribute to a growing body of evidence supporting the use of edaravone as a therapeutic option for ALS. They also underscore the importance of continued data collection from both clinical trials and clinical settings to inform optimal treatment strategies and combination therapy approaches as more agents become available in an evolving ALS treatment landscape.},
}

Humans
*Amyotrophic Lateral Sclerosis/drug therapy
*Edaravone/therapeutic use
*Clinical Trials as Topic
*Free Radical Scavengers/therapeutic use/administration & dosage

@article {pmid41653008,
year = {2026},
author = {Brooks, BR and Ennist, DL and Beaulieu, D and Apple, S},
title = {Generalizability of Edaravone Efficacy.},
journal = {Muscle & nerve},
volume = {73 Suppl 1},
number = {Suppl 1},
pages = {S16-S18},
pmid = {41653008},
issn = {1097-4598},
support = {//Mitsubishi Tanabe Pharma America, Inc./ ; },
mesh = {Humans ; *Edaravone/therapeutic use ; *Amyotrophic Lateral Sclerosis/drug therapy/physiopathology ; Male ; Female ; Middle Aged ; *Free Radical Scavengers/therapeutic use ; Treatment Outcome ; Aged ; Disease Progression ; Retrospective Studies ; Vital Capacity/drug effects ; Machine Learning ; },
abstract = {The pivotal phase 3 trial MCI186-19 (Study 19) demonstrated the efficacy of intravenous edaravone in slowing functional decline in patients with amyotrophic lateral sclerosis (ALS), leading to United States Food and Drug Administration approval. Study 19 utilized a targeted enrollment enrichment strategy based on post hoc analyses from earlier trials, selecting patients with higher baseline function, more rapid disease progression, and better respiratory status. To evaluate the generalizability of Study 19 results, subsequent post hoc analyses assessed the efficacy of edaravone in broader ALS populations. One machine learning-based analysis retrospectively applied a validated model to Study 16 data, stratifying patients by predicted risk of respiratory decline. This detectable effect cluster analysis suggested that up to 70% of Study 16 participants may have benefited from edaravone. A second analysis investigated edaravone efficacy in patients from Study 19 with forced vital capacity (FVC) < 80% predicted (%p) at the start of treatment, since FVC ≥ 80%p was one of the Study 19 inclusion criteria. Both high- and low-FVC subgroups demonstrated reduced ALS functional rating scale-revised decline at 48 weeks when treated continuously with edaravone. These findings support the potential benefit of edaravone in a wider range of patients with ALS than those enrolled in Study 19, providing important insights into how clinical trial enrichment strategies may influence perceived efficacy, and underscoring the need for future prospective studies in more diverse ALS populations.},
}

Humans
*Edaravone/therapeutic use
*Amyotrophic Lateral Sclerosis/drug therapy/physiopathology
Male
Female
Middle Aged
*Free Radical Scavengers/therapeutic use
Treatment Outcome
Aged
Disease Progression
Retrospective Studies
Vital Capacity/drug effects
Machine Learning

@article {pmid41653006,
year = {2026},
author = {Gwathmey, KG and Apple, S},
title = {Introduction to the Supplement.},
journal = {Muscle & nerve},
volume = {73 Suppl 1},
number = {Suppl 1},
pages = {S3-S6},
pmid = {41653006},
issn = {1097-4598},
support = {//Mitsubishi Tanabe Pharma America, Inc./ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Edaravone/therapeutic use ; *Neuroprotective Agents/therapeutic use ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neuromuscular disease with marked phenotypic and clinical heterogeneity. Three active pharmaceutical agents are currently approved by the United States Food and Drug Administration (FDA) for ALS: riluzole, edaravone (including intravenous [IV] and oral suspension formulations), and tofersen. Study MCI186-19 (Study 19) was a pivotal, phase 3 randomized controlled trial that demonstrated a significant reduction in physical functional decline vs. placebo in Japanese patients with ALS and contributed to FDA approval of IV edaravone in 2017. Edaravone oral suspension was FDA-approved in May 2022 following the results of Study MT-1186-A01, which showed it was well tolerated with a safety profile consistent with IV edaravone. Following Study 19, the clinical benefit of edaravone has remained an active area of investigation. This supplement presents data from clinical trials, post hoc analyses, and clinical studies that expand understanding of the use of edaravone in broader ALS populations. Topics include safety in clinical practice, generalizability of efficacy, clinical treatment outcomes, and health economics and outcomes research studies. Together, these findings aim to inform clinicians, researchers, and stakeholders regarding the evolving evidence base for edaravone in the management of ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/drug therapy
*Edaravone/therapeutic use
*Neuroprotective Agents/therapeutic use

@article {pmid41653005,
year = {2026},
author = {Genge, A and Apple, S},
title = {Safety of Intravenous Edaravone in Clinical Practice.},
journal = {Muscle & nerve},
volume = {73 Suppl 1},
number = {Suppl 1},
pages = {S13-S15},
pmid = {41653005},
issn = {1097-4598},
support = {//Mitsubishi Tanabe Pharma America, Inc./ ; },
mesh = {Humans ; Edaravone/adverse effects/administration & dosage ; *Amyotrophic Lateral Sclerosis/drug therapy ; Male ; Female ; *Free Radical Scavengers/adverse effects/administration & dosage ; Middle Aged ; Administration, Intravenous ; Pharmacovigilance ; Aged ; *Antipyrine/analogs & derivatives/adverse effects/administration & dosage ; Adult ; Product Surveillance, Postmarketing ; },
abstract = {This article summarizes the post-marketing pharmacovigilance safety data of intravenous (IV) edaravone during the 1- and 3-year periods following its launch for amyotrophic lateral sclerosis (ALS) in the United States. The most frequently reported adverse events (AEs) and serious AEs (SAEs) included those consistent with ALS disease progression, such as fatigue and muscular weakness, and were not qualitatively different from those reported in previous ALS trials. There were AEs and SAEs associated with IV administration, such as administration site reactions, and five non-fatal anaphylaxis SAEs were reported. No new safety signals were identified, and IV edaravone continues to demonstrate a favorable safety profile. These insights are especially useful as treatment transitions to edaravone oral suspension, which avoids IV-related complications. These findings underscore the importance of ongoing clinical safety assessments in informing ALS treatment decisions.},
}

Humans
Edaravone/adverse effects/administration & dosage
*Amyotrophic Lateral Sclerosis/drug therapy
Male
Female
*Free Radical Scavengers/adverse effects/administration & dosage
Middle Aged
Administration, Intravenous
Pharmacovigilance
Aged
*Antipyrine/analogs & derivatives/adverse effects/administration & dosage
Adult
Product Surveillance, Postmarketing

@article {pmid41653004,
year = {2026},
author = {Brooks, BR and Berry, JD and Ciepielewska, M},
title = {Survival of Intravenous Edaravone-Treated Patients With ALS: Evidence From Administrative Claims Analyses.},
journal = {Muscle & nerve},
volume = {73 Suppl 1},
number = {Suppl 1},
pages = {S23-S25},
pmid = {41653004},
issn = {1097-4598},
support = {//Mitsubishi Tanabe Pharma America, Inc./ ; },
mesh = {Humans ; *Edaravone/administration & dosage/therapeutic use ; *Amyotrophic Lateral Sclerosis/drug therapy/mortality ; Female ; Male ; Middle Aged ; Retrospective Studies ; Aged ; *Free Radical Scavengers/administration & dosage/therapeutic use ; Administration, Intravenous ; Adult ; Neuroprotective Agents ; Databases, Factual ; United States ; Treatment Outcome ; },
abstract = {Randomized controlled trials remain the cornerstone of evidence generation in amyotrophic lateral sclerosis (ALS), yet their inherent challenges, including disease rarity, heterogeneity, and limited validated biomarkers, highlight the need for complementary clinical evidence. This exploratory, retrospective study assessed overall survival in patients with ALS treated with intravenous (IV) edaravone using data from a large United States administrative claims database of patients enrolled from August 2017 to March 2020. Patients receiving IV edaravone (n = 318) were propensity score matched 1:1 with controls not treated with IV edaravone (n = 318), adjusting for 11 covariates. Median overall survival was 29.5 versus 23.5 months for the edaravone-treated group compared to controls, with a 27% reduced risk of death observed in the treated cohort (p = 0.005). These findings, together with existing data from the pivotal phase 3 Study MCI186-19 of IV edaravone, contribute to the growing body of literature suggesting a dual benefit of edaravone on both function and survival in ALS, offering critical insights for clinicians, patients, and payers navigating ALS treatment decisions.},
}

Humans
*Edaravone/administration & dosage/therapeutic use
*Amyotrophic Lateral Sclerosis/drug therapy/mortality
Female
Male
Middle Aged
Retrospective Studies
Aged
*Free Radical Scavengers/administration & dosage/therapeutic use
Administration, Intravenous
Adult
Neuroprotective Agents
Databases, Factual
United States
Treatment Outcome

@article {pmid41653003,
year = {2026},
author = {Brooks, BR and Shefner, J and Apple, S},
title = {Study 19 (MCI186-19) Post Hoc Analyses.},
journal = {Muscle & nerve},
volume = {73 Suppl 1},
number = {},
pages = {S19-S22},
doi = {10.1002/mus.70039},
pmid = {41653003},
issn = {1097-4598},
support = {//Mitsubishi Tanabe Pharma America, Inc./ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Edaravone/therapeutic use ; Treatment Outcome ; Disease Progression ; Male ; Female ; *Free Radical Scavengers/therapeutic use ; Randomized Controlled Trials as Topic ; Middle Aged ; *Neuroprotective Agents/therapeutic use ; },
abstract = {While randomized controlled trials (RCTs) are the gold standard for evaluating the efficacy of therapies in amyotrophic lateral sclerosis (ALS), post hoc analyses can provide critical insights into clinical effectiveness, treatment durability, and subpopulation responses. Several post hoc analyses of Study MCI186-19 (Study 19), the pivotal phase 3 RCT that supported the United States Food and Drug Administration approval of intravenous edaravone, have been performed to explore the broader clinical impact of this therapy. These analyses assessed the long-term treatment efficacy, changes in individual ALS Functional Rating Scale-Revised item scores, survival and additional milestone events, and the impact of edaravone in patient subgroups defined by disease progression trajectories using latent class analysis. Collectively, these findings reinforce the long-term clinical benefit of edaravone and demonstrate that edaravone may offer benefits across a spectrum of ALS disease trajectories, beyond those defined in the original study criteria. These studies help address questions not captured in the original RCT and may inform future trial design and treatment decisions.},
}

Humans
*Amyotrophic Lateral Sclerosis/drug therapy
*Edaravone/therapeutic use
Treatment Outcome
Disease Progression
Male
Female
*Free Radical Scavengers/therapeutic use
Randomized Controlled Trials as Topic
Middle Aged
*Neuroprotective Agents/therapeutic use

@article {pmid41652471,
year = {2026},
author = {Scekic-Zahirovic, J and Antonucci, S and Wiesner, D and Ebner, C and El Hajj, H and Aousji, O and Halablab, K and Fan, Y and Zelaya, A and Yartas, G and Baskar, K and Çakmak, EA and Bayer, D and Sung, HK and Dupuis, L and Park, J and Roselli, F},
title = {Large-scale mapping of the MCH network in ALS mice reveals the vulnerability of dopaminergic and GABAergic neurons in zona incerta.},
journal = {Acta neuropathologica communications},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40478-026-02231-z},
pmid = {41652471},
issn = {2051-5960},
}

@article {pmid41652348,
year = {2026},
author = {Johansen, H and Nakken, O and Holmøy, T and Fredheim, OMS},
title = {Disease trajectories and end of life care in a Norwegian ALS cohort.},
journal = {BMC neurology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12883-026-04698-8},
pmid = {41652348},
issn = {1471-2377},
abstract = {OBJECTIVE: This retrospective cohort study aims to provide comprehensive data on the disease trajectory and end-of-life care in patients dying from ALS.

METHODS: The study presents detailed information on a cohort dying from ALS in the area served by Akershus University Hospital from 2011 to 2022. Data was obtained from the patient medical records.

RESULTS: 118 patients were included. 65 patients (55%) were referred to the Department of Palliative medicine for specialist palliative care, with a median duration from referral to death of two months and one third of patients not being able to communicate verbally at the time of referral. The most common life-sustaining treatment was non-invasive ventilation and percutaneous endoscopic gastrostomy, whereas most prevalent limitation of life-sustaining treatment was withholding of tracheostomy with invasive ventilation. Hospital was the most common place of death with 54 (46%) of all deaths. For in-hospital-deaths, the most common place of death was the palliative care ward, with 21 patients (39%), but a substantial proportion (17%) died at intensive or intermediate care units. Overall, 37% of in-hospital deaths had been admitted to either intensive or intermediate care units during their last week of life, which may suggest these patients deteriorated rapidly without having documented advanced care planning and therefore received resource demanding and futile treatment during the last week of life.

CONCLUSION: Many patients lived in their own homes until admitted to their last hospital stay in life. However, these last hospital stays were frequently characterized by insufficient advanced care planning, leading to futile overtreatment.

TRIAL REGISTRATION: Retrospectively registered.},
}

@article {pmid41651385,
year = {2026},
author = {Raina, GS and Mehan, S and Das Gupta, G},
title = {Neuroprotection via IGF-1 Neuronal Signaling Activation by Melatonin and Edaravone Synergy in Methylmercury-Induced ALS-like Neurotoxicity: Comprehensive Analysis of Brain Regions, Spinal Cord, CSF, and Blood Plasma.},
journal = {Neurotoxicology},
volume = {},
number = {},
pages = {103398},
doi = {10.1016/j.neuro.2026.103398},
pmid = {41651385},
issn = {1872-9711},
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease characterized by motor neuron degeneration, oxidative stress, neuroinflammation, and neurotransmitter imbalances. This study explored the neuroprotective potential of melatonin (MLT), alone and in combination with edaravone (EDR), in a methylmercury (MEME)-induced ALS rat model. MEME exposure effectively replicated ALS pathology, causing behavioral deficits, oxidative stress, neuroinflammation, apoptosis, and widespread structural damage in critical brain regions and the spinal cord. MLT administration at 5mg/kg (MLT5) and 10mg/kg (MLT10) significantly mitigated MEME-induced neurotoxicity in a dose-dependent manner. MLT improved motor function, reduced depressive-like behavior, and restored body weight. Biochemically, MLT enhanced antioxidant defenses, including superoxide dismutase (SOD) and catalase (CAT), reduced pro-inflammatory cytokines, interleukin-1 beta (IL-1β), increased anti-inflammatory cytokines, interleukin-10 (IL-10), and restored neurotransmitter balance like dopamine and Gamma-Aminobutyric Acid (GABA). Mechanistically, MLT activated the IGF-1 signaling pathway, promoting neuronal survival and reducing apoptosis (Caspase-3 expression). Histopathological analyses confirmed that MLT preserved neuronal and glial integrity, reduced demyelination, and restored myelin basic protein (MBP) levels in brain and cerebrospinal fluid. The combination of MLT and EDR exhibited synergistic neuroprotective effects, surpassing the efficacy of individual treatments in reducing oxidative stress, inflammation, and neuronal damage. Behavioral and biochemical improvements were paralleled by systemic recovery, as evidenced by normalized hematological parameters and reduced methylmercury accumulation in brain tissues. These findings underscore MLT, particularly in combination with EDR, as a potent therapeutic agent for ALS, offering multi-targeted neuroprotection. Future studies should explore its translational potential in clinical settings for the treatment of neurodegenerative diseases.},
}

@article {pmid41651252,
year = {2026},
author = {Hnath, B and Ekambaram, S and Dokholyan, NV},
title = {Novel extracellular vesicle release pathway facilitated by toxic superoxide dismutase 1 oligomers.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107309},
doi = {10.1016/j.nbd.2026.107309},
pmid = {41651252},
issn = {1095-953X},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that results in paralysis and death within three to five years. Mutations in over forty different proteins have been linked to ALS, raising debate over whether ALS is a single disease or multiple disorders with similar symptoms. Mutations in Cu,Zn superoxide dismutase 1 (SOD1) are found in only 2-3% of ALS cases, yet misfolded SOD1 appears in both sporadic (sALS) and familial (fALS) patients. Furthermore, mutations in TDP-43 or FUS increase levels of misfolded SOD1 on extracellular vesicles (EVs). Small EVs isolated from ALS patient samples have been shown to cause death of wild-type motor neurons and myotubes, supporting the theory that EVs play a role in spreading disease. We hypothesize that the previously identified toxic trimeric SOD1 spreads via EVs in ALS and influences the distribution of other ALS-related proteins, suggesting a common mechanism. To test this, we isolate EVs from motor neuron-like cells expressing mutations that stabilize trimers. We then perform a sandwich enzyme-linked immunosorbent assay (ELISA) using a CD9 capture antibody to measure whether misfolded SOD1 and 17 other ALS-related proteins increase or decrease on EVs with trimer stabilization. We identify which EV release pathway is affected by trimeric SOD1 using endocytosis and exocytosis inhibitors and analyze altered protein interaction pathways through co-immunoprecipitation and mass spectrometry proteomics. Our results show that VAPB, VCP, and Stathmin-2 increase on EVs when trimers are stabilized. The common pathway linking these ALS-associated proteins and SOD1 appears to involve multiple mechanisms, including the Caveolae endocytosis pathway, pointing to a novel hybrid EV release pathway in ALS. Overall, our findings show that trimeric SOD1 influences EV cargo and spread in ALS.},
}

@article {pmid41649950,
year = {2026},
author = {Komori, S and Ito, D and Hashizume, A and Yamada, S and Kishimoto, Y and Kawase, T and Kondo, A and Suzuki, M and Hatanaka, M and Oba, C and Katsuno, M},
title = {Characteristics of muscle cramps as a prodromal symptom of sporadic amyotrophic lateral sclerosis.},
journal = {Journal of neuromuscular diseases},
volume = {},
number = {},
pages = {22143602261422971},
doi = {10.1177/22143602261422971},
pmid = {41649950},
issn = {2214-3602},
abstract = {BACKGROUND: Prodromal symptoms of sporadic amyotrophic lateral sclerosis (SALS) including muscle cramps were reported; however, their detailed characteristics have not been sufficiently studied.

OBJECTIVES: To clarify the detailed profiles of prodromal symptoms in SALS.

METHODS: Patients with SALS (n = 47) and healthy controls (n = 25) were enrolled. A questionnaire-based survey was conducted to investigate symptoms before and after disease onset, including sensory, autonomic, sleep, cognitive disturbances, and frequent muscle cramps. Frequent muscle cramps were defined as those occurring at least twice per month in the lower limbs, or at least once per month in the upper limbs or trunk. We evaluated the relationship between surveyed symptoms and clinical characteristics.

RESULTS: Prodromal frequent muscle cramps were observed in 29.8% of SALS patients, most frequently in the lower limbs. With disease progression, the sites with cramps increased, and the frequency of cramps during awakening also increased. The SALS patients with prodromal cramps had greater lean mass than those without (p = 0.023). Multivariate analysis showed that the presence of cramps after disease onset was associated with a slower longitudinal decline in the ALSFRS-R score (p = 0.048). Upper limb-onset SALS patients experienced cramps more frequently before onset than bulbar-onset patients did (p = 0.033).

CONCLUSIONS: Frequent muscle cramps often precede muscle weakness during the prodromal phase of limb-onset SALS. The frequency of cramps increased with disease progression. Prodromal cramps were associated with lean mass, whereas cramps after disease onset were associated with a slower rate of disease progression.},
}

@article {pmid41649614,
year = {2026},
author = {Mukherjee, R and Mehan, S and Choudhary, D and Rana, R and Das Gupta, G and Samant, R and Tongra, M},
title = {Sulforaphane-Mediated Multitarget Therapeutic Effects in Methylmercury-Induced ALS-Like Pathology: Comparative Analysis and Multifaceted Approach to Neuroprotection and Systemic Recovery.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {422},
pmid = {41649614},
issn = {1559-1182},
mesh = {Animals ; *Isothiocyanates/pharmacology/therapeutic use ; Sulfoxides ; *Neuroprotective Agents/pharmacology/therapeutic use ; *Methylmercury Compounds/toxicity ; *Amyotrophic Lateral Sclerosis/drug therapy/pathology/chemically induced/physiopathology ; Female ; Rats ; Rats, Sprague-Dawley ; *Recovery of Function/drug effects ; *Neuroprotection/drug effects ; Male ; Oxidative Stress/drug effects ; Apoptosis/drug effects ; Antioxidants/metabolism ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder marked by motor neuron loss driven by oxidative stress, neuroinflammation, and dysregulated survival signaling. The objective of this study was to evaluate the neuroprotective efficacy and safety of sulforaphane (SUFP) in a methylmercury (MMHg[+])-induced preclinical rat model of ALS, with comparison to omaveloxolone (OVX) and dimethyl fumarate (DIMT). SUFP treatment, particularly at 4 mg/kg, significantly restored antioxidant defense mechanisms through upregulation of Nrf2, HO-1, and SIRT1 while suppressing pro-inflammatory cytokines (IL-1β, TNF-α), apoptotic markers (Bax, caspase-3), and stress-related signaling pathways including p75NTR, PI3K/Akt, and MAPKs. These molecular effects translated into meaningful functional recovery, as evidenced by improvements in grip strength, locomotor performance, spatial memory, and depressive-like behavior. Histopathological evaluation demonstrated attenuation of demyelination and preservation of neuronal architecture in cortical, hippocampal, and cerebellar regions. Beyond central neuroprotection, SUFP exerted systemic benefits by normalizing hepatic enzymes, improving skeletal muscle integrity, restoring redox balance, stabilizing neurofilament and myelin-associated proteins, and correcting hematological alterations. Comparative analysis revealed that SUFP conferred superior neuroprotection with a favorable safety profile relative to OVX and, although slightly less efficacious than DIMT, exhibited reduced systemic toxicity. Molecular docking further supported SUFP's interaction with Nrf2-Keap1 targets, reinforcing its antioxidant and anti-inflammatory mechanisms. Collectively, these findings identify SUFP as a multifaceted and well-tolerated therapeutic candidate for ALS, supporting its further translational and clinical evaluation.},
}

Animals
*Isothiocyanates/pharmacology/therapeutic use
Sulfoxides
*Neuroprotective Agents/pharmacology/therapeutic use
*Methylmercury Compounds/toxicity
*Amyotrophic Lateral Sclerosis/drug therapy/pathology/chemically induced/physiopathology
Female
Rats
Rats, Sprague-Dawley
*Recovery of Function/drug effects
*Neuroprotection/drug effects
Male
Oxidative Stress/drug effects
Apoptosis/drug effects
Antioxidants/metabolism

@article {pmid41647790,
year = {2025},
author = {Raymond, J and Larson, T and Nair, T and Kaufman, J and Horton, DK and Weisskopf, M and Mohidul, S and Mehta, P},
title = {Age-period-cohort effect on motor neuron disease mortality in the United States, 2001-2020.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1751690},
pmid = {41647790},
issn = {1664-2295},
abstract = {INTRODUCTION: Motor neuron diseases (MND) are progressively fatal diseases causing loss of motor neurons throughout the body. Recent studies have suggested an increase in prevalence and mortality of amyotrophic lateral sclerosis (ALS), the most common adult-onset MND. It is unclear whether the increase is because of earlier diagnosis or potentially new exposures. Age-period-cohort (APC) analysis can help identify contributors to temporal disease trends by differentiating impacts of biological aging, historical time period, and birth cohort. The aim of this study is to evaluate APC effects on MND mortality in the United States from 2001 to 2020.

METHODS: We analyzed deaths by MND for the period 2001-2020 in subjects aged 40-84 years. We used APC modeling to compute net drift, local drift, longitudinal age curve, rate ratios (RR), and confidence intervals (CI) for each period and cohort. Analysis used the APC Web Tool provided by the United States' National Cancer Institute.

RESULTS: Over the 20-year period, there were 119,890 MND deaths. Men consistently had higher mortality compared to women. Analysis yielded noteworthy birth cohort effects for men. For men, the cohort RR decreased from 1919 to 1953 and peaked again between 1959 and 1963. Men born after 1973 had a reduced RR = 0.77 (95% CI = 0.63-0.94). Women born after 1973 had a cohort RR = 1.00 (95% CI = 0.75-1.34).

CONCLUSION: APC analysis revealed potentially impactful age, period, and cohort effects in U.S. MND mortality between 2001 and 2020, with higher mortality among men and evidence of sex-specific cohort patterns. Cohort effects suggest potential generational differences in risk. Further investigation is needed to disentangle ascertainment effects from true etiologic influences.},
}

@article {pmid41647265,
year = {2026},
author = {Kim, H},
title = {Task-invariant networks interfere with and task-specific networks support memory formation: An fMRI meta-analysis.},
journal = {Imaging neuroscience (Cambridge, Mass.)},
volume = {4},
number = {},
pages = {},
pmid = {41647265},
issn = {2837-6056},
abstract = {Why do some moments imprint themselves in memory while others vanish without a trace? This meta-analysis identifies a dissociation in large-scale brain networks during encoding: networks associated with impairing encoding are task-invariant, whereas those supporting it are task-specific. Drawing on 56 functional magnetic resonance imaging (fMRI) studies employing the subsequent memory paradigm, the analysis contrasted neural activity for later-remembered versus later-forgotten trials across verbal and pictorial tasks. Using Yeo et al.'s 17-network parcellation, the results show that encoding-impairing effects consistently recruit specific subsystems within the default mode, frontoparietal, and ventral attention networks-a pattern consistent with distraction or mind-wandering. Conversely, encoding-supporting effects diverge by task: verbal encoding engages language-related networks, whereas pictorial encoding activates visuo-perceptual systems. This asymmetry suggests that encoding failure may arise from similar attentional lapses across contexts, whereas successful encoding requires precise, context-sensitive neural engagement. Taken together, these findings provide a network-level perspective on how the brain shifts between states conducive to remembering and states conducive to forgetting.},
}

@article {pmid41646446,
year = {2026},
author = {Donkin, A and Rodseth, R and Giddy, J},
title = {FDNHSA's response to KL Dunkle et al.'s 'Upholding clinical integrity and South African relevance: A defence of the SASOP position statement on the care of transgender and non-binary youth'.},
journal = {The South African journal of psychiatry : SAJP : the journal of the Society of Psychiatrists of South Africa},
volume = {32},
number = {},
pages = {2602},
pmid = {41646446},
issn = {1608-9685},
}

@article {pmid41646374,
year = {2026},
author = {Cropper, H and Mir, F and Liu, J and Srivastava, V and Ramizuddin, M and Kopecky, K and Mocanu, E and Dachet, F and Jiang, QL and Soni, M and Valyi-Nagy, T and Mnatsakanova, D and Abrams, C and Song, F and Loeb, J},
title = {Axonal dying back of upper motor neurons in human ALS.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-8545414/v1},
pmid = {41646374},
issn = {2693-5015},
abstract = {Patients with amyotrophic lateral sclerosis (ALS) present with arm, leg, or bulbar weakness with or without spasticity. While genetics plays a clear role in a subset of cases, it cannot explain why symptoms start focally or how upper (UMN) and lower motor neuron (LMN) systems are linked. Here, we examined the clinicopathological relationships between UMN and LMN disease in ten ALS patients. Detailed clinical assessments were obtained and tissues from the motor cortex, brainstem, and spinal cord were collected via a rapid autopsy protocol. Tissues were stained for UMN/LMN, myelin, axons, microglia, and pTDP43. Total RNA-sequencing was performed in the medulla, cervical, and lumbar spinal cords from each patient to identify pathways enriched at sites of disease onset. None of the patients had symptoms of frontotemporal dementia (FTD), but all had focal sites of clinical onset and spasticity, indicating both UMN and LMN involvement. Postmortem examination showed LMN degeneration and microglial activation were highest at sites of disease onset. In contrast, UMN degeneration of the corticospinal tract (CST) was present equally at all levels of the spinal cord up through the medulla, regardless of the site of disease onset. Surprisingly, there was no evidence of UMN degeneration of cortical motor neurons or their projecting axons above the brainstem. Similarly, while extensive pTDP43 aggregates were seen in degenerating LMNs, no pTDP43 aggregates were seen in UMN cell bodies or their axons. Mechanistically, RNA-sequencing implicated inflammatory pathways, especially at sites of disease onset. Our findings suggest that many ALS patients without FTD have a dying back of UMN axons, independent of the site of disease onset, which stops in the brainstem with preservation of cortical motor neurons and their proximal axons. Our findings suggest that UMN axonal degeneration can be directly triggered by LMN degeneration and inflammation.},
}

@article {pmid41646275,
year = {2025},
author = {Naddaf, R and Shmilovich, H and Carasso, S and Keshet-David, R and Herren, R and Gefen, T and Goshen-Lago, T and Zwang, Y and Livyatan, I and Shental, N and Haberfeld, O and Straussman, R and Markar, SR and Nilsson, M and Kashtan, H and Ben-Aharon, I and Geva-Zatorsky, N},
title = {Esophageal microbiome correlates with post-esophagectomy anastomotic leak in cancer patients.},
journal = {ESMO gastrointestinal oncology},
volume = {8},
number = {},
pages = {100172},
pmid = {41646275},
issn = {2949-8198},
abstract = {BACKGROUND: Despite continuous improvement in long-term survival after esophagectomy, potential serious post-operative complications, such as anastomotic leaks (ALs), still occur. Several risk factors for ALs have been proposed, including environmental factors. Our main objective was to examine the correlation of esophageal tumor microbiome composition and functional profile with ALs. Additionally, we analyzed the microbiome of esophageal tumors and their potential correlation with clinical features of the patients.

MATERIALS AND METHODS: Surgical specimens of esophageal tumors and adjacent normal tissues were collected from consecutive patients who underwent an esophagectomy. Formalin-fixed paraffin-embedded (FFPE) tissue samples were processed using 16S ribosomal DNA multiple fragments amplicon sequencing to characterize bacterial microbiome composition. The tumor and normal tissue microbiome and bacterial functional profile were analyzed based on the clinical outcome of ALs.

RESULTS: Out of 60 patients who met the inclusion criteria, 52 (86.7%) patients had both normal adjacent tissue (NAT) and tumor (T) FFPE samples included with sufficient bacterial DNA extracted for analysis. A total of 28% of participants had esophageal ALs. Proportion tests [P < 0.05, false discovery rate (FDR) < 0.25] revealed operational taxonomic units (OTUs) significantly present in T samples as opposed to NAT samples, as well as significantly present OTUs in patients with AL as opposed to patients without AL complication.

CONCLUSIONS: In this study, we provide a profile of the understudied esophageal microbiome and its connection to ALs. Our results can provide potential clues on how to avoid ALs by considering a patient's personal microbiome when providing perioperative care.},
}

@article {pmid41646005,
year = {2026},
author = {Peng, J and Fan, T and Wang, J and Deng, Y and Xu, R},
title = {Current potential biomarkers for Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis: review of literature.},
journal = {Dialogues in clinical neuroscience},
volume = {28},
number = {1},
pages = {17-39},
doi = {10.1080/19585969.2026.2622722},
pmid = {41646005},
issn = {1958-5969},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/diagnosis/blood/metabolism ; *Biomarkers/cerebrospinal fluid/blood ; *Alzheimer Disease/diagnosis/blood/metabolism/cerebrospinal fluid ; *Parkinson Disease/diagnosis/blood/metabolism/cerebrospinal fluid ; },
abstract = {INTRODUCTION: Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS) are several common neurodegenerative diseases (NDs). At present, is the lack of effective diagnosis, progression, prognosis and therapeutic biomarkers. it is a urgent demand to search the relevant confident biomarkers.

AREA COVERED: This review systematically analysed the potential biomarkers of blood, cerebrospinal fluid, neuroimaing and emerging non-invasive indicators, and synthesises current evidences on the biomarkers of AD, PD and ALS about diagnosis, progression, prognosis and therapeutic, especially diagnosis biomarkers.

EXPERT COMMENTARY: In this review, we focus on discussing relevant diagnosis, progression, prognosis and therapeutic biomarkers for AD, PD and ALS in recent years, and prospecting the possible future directions of relevant biomarkers.},
}

Humans
*Amyotrophic Lateral Sclerosis/diagnosis/blood/metabolism
*Biomarkers/cerebrospinal fluid/blood
*Alzheimer Disease/diagnosis/blood/metabolism/cerebrospinal fluid
*Parkinson Disease/diagnosis/blood/metabolism/cerebrospinal fluid

@article {pmid41645941,
year = {2026},
author = {Iammeechai, W and Srikulmontri, T and White, BAA},
title = {Emotional intelligence development in medical education: A scoping review of educational interventions.},
journal = {Medical teacher},
volume = {},
number = {},
pages = {1-14},
doi = {10.1080/0142159X.2026.2621214},
pmid = {41645941},
issn = {1466-187X},
abstract = {Background and aims: Emotional intelligence (EI) is an essential competency for physicians. Medical educators seek educational interventions to cultivate EI in their learners. This scoping review aimed to conceptualize current knowledge about educational interventions for developing EI in medical education. Methods: This study adopted the first five stages of Levac et al.'s scoping review framework, which builds on Arksey and O'Malley's scoping review methodology. The authors accessed three databases-PubMed, CINAHL, and PsycINFO-to review the literature from 2014 to February 2025. Two authors (WI and TS) independently screened the literature for eligibility. A third author (BAAW) resolved any discrepancies. Two authors (WI and BAAW) charted the eligible articles. Results: Of the 638 studies, 64 were eligible. Approximately one-third of eligible studies focused on interventions for medical students. Stress management, leadership, communication, and professionalism were key topics integrated into EI development interventions. Various methods were employed, such as small-group discussions, case-based discussions, and simulations. Most studies used self-rating questionnaires as assessment tools. Half of the studies (56.25%) reported positive impacts from their interventions. Conclusions: The findings could serve as a guide for educators and researchers seeking to implement or study such interventions.},
}

@article {pmid41645155,
year = {2026},
author = {McDonald, DW and Chugh, N and Sava, R and Duennwald, ML},
title = {FUS and TDP-43 aggregation are uncoupled from toxicity in ageing yeast models.},
journal = {BMC biology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12915-026-02537-3},
pmid = {41645155},
issn = {1741-7007},
support = {RGPIN-2024-05867//Natural Sciences and Engineering Research Council of Canada/ ; },
abstract = {BACKGROUND: Protein aggregation is indicative of the loss of proteostasis associated with neurodegenerative diseases, including Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD). Proteins like Fused in sarcoma (FUS) and Tar DNA-binding protein 43 (TDP-43) accumulate and aggregate in the cytosol of neurons in ALS/FTD. Yet, it remains unclear how ageing affects FUS and TDP-43 aggregation, and how these aggregates in turn influence neurodegeneration in ALS/FTD. In addition, mistranslation can reduce longevity, challenge proteostasis, and modulate protein aggregation. To investigate how ageing and mistranslation modulate FUS and TDP-43 aggregation and toxicity, we enlist tractable and reliable yeast models.

RESULTS: Using optimized low-expression FUS and TDP-43 yeast models, we demonstrate that chronological ageing antagonizes proteostasis, the steady state levels and solubility of molecular chaperones, and aggregation of FUS and TDP-43. In addition, mistranslation caused by tRNA variants further antagonize FUS and TDP-43 aggregation and synergize to exacerbate FUS and TDP-43 cytotoxicity.

CONCLUSIONS: Our work provides new insights into factors that uncouple FUS and TDP-43 aggregation from toxicity and support a rather protective role for FUS and TDP-43 aggregates in promoting longevity.},
}

@article {pmid41643661,
year = {2026},
author = {Liu, H and Liu, M and Liu, Y and Gui, G and Paul, T and Lu, YN and Huang, Z and Wang, H and Xiao, Y and Zheng, Z and Periz, G and Shi, Y and Ichida, JK and Myong, S and Ji, H and Wang, J},
title = {C9orf72 hexanucleotide repeat RNA drives transcriptional dysregulation through genome-wide DNA:RNA hybrid G-quadruplexes.},
journal = {Neuron},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuron.2025.12.005},
pmid = {41643661},
issn = {1097-4199},
abstract = {A hexanucleotide repeat expansion in C9orf72 is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. While repeat RNAs are implicated in disease pathogenesis, their mechanisms of action remain incompletely understood. Here, we show that GGGGCC repeat RNA engages chromatin genome-wide preferentially at promoter regions in patient cells. This interaction obstructs RNA polymerase II and transcription factors with GC-rich motifs, leading to broad transcriptional repression. Biochemical assays, single-molecule imaging, and native bisulfite sequencing analyses demonstrate that GGGGCC repeat RNA intrinsically forms DNA:RNA hybrid G-quadruplexes (HQs) with cognate DNA, providing a structural basis for transcriptional interference. Stabilization of these G-quadruplex structures exacerbates neuronal vulnerability to metabolic stress in patient-derived motor neurons and cortical organoids, whereas restoring key gene dysregulation improves resistance. These findings uncover a previously unrecognized trans-acting mechanism whereby repetitive RNAs form hybrid structures with genomic DNA, disrupt gene regulation, and contribute to neurodegeneration.},
}

@article {pmid41643607,
year = {2026},
author = {Cásedas, G and Rojas-Márquez, H and Ventura, L and Moliner, C and Maggi, F and Rubio-Castellanos, A and López, V},
title = {Involvement of Keap1/Nrf2 and the antioxidant defence in cytoprotective effects induced by cannabis polyphenols in SH-SY5Y neuronal cells.},
journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie},
volume = {196},
number = {},
pages = {119048},
doi = {10.1016/j.biopha.2026.119048},
pmid = {41643607},
issn = {1950-6007},
abstract = {Oxidative stress (OS) is widely recognized as a central promoter to the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS). Cannabis sativa L. synthesizes a complex array of bioactive compounds that extends well beyond the well-known cannabinoids to include a diverse suite of polyphenols, terpenes, fatty acids, tocopherols, and proteins. The non-cannabinoid polyphenolic fraction is composed primarily of flavonoids, stilbenoids, lignans, and lignanamides, which contribute substantially to the plant's antioxidant, anti-inflammatory, and neuroprotective properties. This study investigates the redox-modulating and cytoprotective properties of a polyphenolic fraction derived from Cannabis sativa L. in SH-SY5Y neuroblastoma cells. Neurons were treated with various concentrations of the aqueous polyphenolic cannabis extract and exposed to oxidative stress using hydrogen peroxide (100 µM). Protein and gene expression related to redox signalling were analyzed via Western blot and qPCR, and molecular docking studies were performed in silico. Furthermore, antioxidant enzymes activity was measured by spectrophotometry. Results revealed that the phenolic fraction significantly activated the Keap1/Nrf2 pathway, increased expression of PRDX1 and PRDX3, and enhanced endogenous antioxidant defences. Simultaneously, it reduced endoplasmic reticulum stress-induced apoptosis (via Bax/Bcl-2 modulation) and attenuated inflammatory markers, including NO, NF-κB2, IL-6, and IL-8. In silico docking studies identified Leu583 as a key residue in Nrf2-ligand interactions. These findings suggest that Cannabis sativa L. polyphenols are key bioactive compounds modulating redox homeostasis and inflammation, and offering neuroprotective benefits with potential relevance in diseases involving mitochondrial dysfunction and oxidative damage.},
}

@article {pmid41643564,
year = {2026},
author = {Ma, Z and Zheng, J and Wang, H and Chen, C and Yue, J and Duan, X and Jiang, H},
title = {A Novel Classification of Esophageal Anastomotic Leaks and Its Impact on Healing Time After Esophagogastrostomy.},
journal = {Cancer research and treatment},
volume = {},
number = {},
pages = {},
doi = {10.4143/crt.2025.1029},
pmid = {41643564},
issn = {2005-9256},
abstract = {PURPOSE: Anastomotic leakage (AL) is a severe complication after esophagogastrostomy, yet the classifications of AL and their associated healing times are poorly understood.

MATERIALS AND METHODS: This study retrospectively analyzed 117 cases of AL among 2,728 patients who underwent esophagectomy with circular stapled esophagogastric anastomosis at Tianjin Medical University Cancer Institute and Hospital from January 1, 2019, to March 31, 2024. AL cases were categorized into four types based on the direction of leakage (anterior, right, posterior, and left). The differences in healing times among these four types were analyzed using the log-rank test. A multivariable Cox model was used to identify factors associated with healing time.

RESULTS: The incidence of AL was 4.3% (117/2728), with a median occurrence time of 9 days (Interquartile Range[IQR]: 5) and a median healing time of 56 days (IQR:64). Single cervical ALs accounted for 17.5%, with significantly shorter healing times compared to intrathoracic leaks (33 days vs. 61 days, p=0.018). Right-sided leaks were the most common (49.6%), while left-sided leaks healed faster than right- and posterior-sided leaks (42 days vs. 63 days vs. 70 days, p<0.05). Body Mass Index (BMI), diabetes, and neoadjuvant therapy did not influence healing time. In 117 AL patients, the occurrence of tracheoesophageal fistula (p=0.004) and the placement of trans-fistula reverse drainage tubes (p=0.002) were associated with healing time.

CONCLUSION: These findings provide valuable insights for clinicians to better understand the mechanisms of AL development and predict the healing times.},
}

@article {pmid41643078,
year = {2026},
author = {Fernandez, R and Sívori, M},
title = {[Clinical scale of ventilatory failure risk in patients with amyotrophic lateral sclerosis].},
journal = {Medicina},
volume = {86},
number = {1},
pages = {60-72},
pmid = {41643078},
issn = {1669-9106},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/mortality/physiopathology ; Male ; Retrospective Studies ; Female ; Middle Aged ; *Hypercapnia/etiology ; *Respiratory Insufficiency/etiology/mortality ; Aged ; Risk Factors ; Risk Assessment/methods ; Prognosis ; Respiration, Artificial ; Dyspnea/etiology ; },
abstract = {INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that causes atrophy and paralysis of skeletal muscles, including respiratory muscles. The development of ventilatory failure determines the prognosis. The primary outcome was to determine which common clinical variables can be predictors of daytime hypercapnia and develop a risk model of ventilatory failure. Secondary outcome was to determinate the survival rate of high-risk patients with and without hypercapnia.

MATERIALS AND METHODS: Retrospective study. Patients with ALS without mechanical ventilation were selected and followed from June 2015 to May 2024. They underwent arterial blood carbon dioxide measurement and classified into two groups: hypercapnic (pCO2 ≥45 mmHg) and normocapnic (pCO2 <45 mmHg). Different predictive models for hypercapnia were constructed.

RESULTS: An association between orthopnea (p=0.0001), dyspnea (p=0.02) and FVC <50% (p=0.04) was found. The predictive model constructed with the following variables: orthopnea, dyspnea and ALSFRS-R score ≤21, presented a good performance on the detection hypercapnia risk. A score > 23 points had a sensitivity of 80.6% and a specificity of 72.8% for detecting patients at high risk of hypercapnia. Normocapnic patients at high risk who start mechanical ventilation before developing hypercapnia improve their survival rate by 6 months (p=0.17).

DISCUSSION: The risk score includes easily obtained clinical variables and is effective in detecting patients at risk for hypercapnia. Initiating mechanical ventilation in at-risk patients who have not yet developed hypercapnia has a clinically significant impact on survival.},
}

Humans
*Amyotrophic Lateral Sclerosis/complications/mortality/physiopathology
Male
Retrospective Studies
Female
Middle Aged
*Hypercapnia/etiology
*Respiratory Insufficiency/etiology/mortality
Aged
Risk Factors
Risk Assessment/methods
Prognosis
Respiration, Artificial
Dyspnea/etiology

@article {pmid41643021,
year = {2026},
author = {Jiang, X and Schaeffer, L and Patni, D and Russo, T and Lee, CZ and Aguilar, C and Marques, C and Jansen-West, K and Hruska-Plochan, M and Ray-Soni, A and Lim, SM and Held, A and Yue, M and Castellanos Otero, P and Aryal, S and Beaussant, HDAM and Basu, H and Takakuwa, H and Daughrity, LM and Ramesh, N and Da Costa, P and A A Quadros, AR and Nolan, M and Reyes, CJF and Wheeler, H and Moran, LC and Griesman, G and Wymann, B and Trombetta, BA and Lopez-De-Silanes, ES and Canori, M and Krishnan, G and Vieira Souza Da Silva, Y and Eriani, G and Albers, MW and Arnold, SE and Song, Y and Jain, A and Chiu, IM and Zhang, YJ and Gao, FB and Wainger, BJ and Polymenidou, M and Petrucelli, L and Martin, F and Lagier-Tourenne, C},
title = {Blocking RAN translation without altering repeat RNAs rescues C9ORF72-related ALS and FTD phenotypes.},
journal = {Science (New York, N.Y.)},
volume = {391},
number = {6785},
pages = {eadv2600},
doi = {10.1126/science.adv2600},
pmid = {41643021},
issn = {1095-9203},
mesh = {*Amyotrophic Lateral Sclerosis/genetics/pathology/therapy ; *Frontotemporal Dementia/genetics/pathology/therapy ; *C9orf72 Protein/genetics ; Animals ; Mice ; Humans ; *Protein Biosynthesis ; DNA Repeat Expansion ; Phenotype ; Induced Pluripotent Stem Cells ; Motor Neurons/pathology ; DNA-Binding Proteins/metabolism ; *RNA/genetics/metabolism ; Disease Models, Animal ; *ran GTP-Binding Protein/genetics ; Dipeptides/genetics ; Codon ; Mutation ; },
abstract = {GGGGCC (G4C2) repeat expansion in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Toxicity is thought to result from the accumulation of either repeat RNAs and/or dipeptide repeat proteins (DPRs) translated from repeat-containing transcripts through repeat-associated non-AUG (RAN) translation. To disentangle RNA from DPR toxicity, we mutated a CUG codon predominantly used to initiate DPR translation from all three reading frames. This mutation disrupted DPR synthesis while preserving the expression of repeat-containing RNAs. Despite the accumulation of RNA foci, behavioral deficits and pathological abnormalities, including p-TDP-43 inclusions, STING activation, motor neuron loss, neuroinflammation, and increased plasma neurofilament concentration, were alleviated in C9ORF72 mice. Base editing of the CUG codon also improved molecular phenotypes and survival in patient induced pluripotent stem cell-derived neurons, which highlights the potential of therapeutically targeting DPR production rather than repeat RNAs.},
}

*Amyotrophic Lateral Sclerosis/genetics/pathology/therapy
*Frontotemporal Dementia/genetics/pathology/therapy
*C9orf72 Protein/genetics
Animals
Mice
Humans
*Protein Biosynthesis
DNA Repeat Expansion
Phenotype
Induced Pluripotent Stem Cells
Motor Neurons/pathology
DNA-Binding Proteins/metabolism
*RNA/genetics/metabolism
Disease Models, Animal
*ran GTP-Binding Protein/genetics
Dipeptides/genetics
Codon
Mutation

@article {pmid41642988,
year = {2026},
author = {Wells, TL and Galani, M and Popoli, R and Zagoraiou, L and Akay, T},
title = {Compensatory scaling of modulatory neural populations in response to motor challenges.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {123},
number = {6},
pages = {e2519741123},
doi = {10.1073/pnas.2519741123},
pmid = {41642988},
issn = {1091-6490},
mesh = {Animals ; Mice ; *Motor Neurons/physiology/metabolism ; *Interneurons/physiology/metabolism ; Spinal Cord/physiology/metabolism ; Serotonin/metabolism ; Brain Stem/physiology/metabolism ; Muscle, Skeletal/physiology ; Locomotion/physiology ; Cholinergic Neurons/physiology/metabolism ; Male ; Electromyography ; },
abstract = {Precise and adaptable movements are achieved by well-regulated muscle contractions, which are mainly governed by the excitability of motor neurons. Several neuromodulatory systems originating in the motor cortex, brainstem, and spinal cord regulate motor neuron excitability via the release of neurotransmitters such as acetylcholine and serotonin. However, these systems can have seemingly similar effects on motor neuron output, raising questions about interaction during movement. To address this, we investigated two modulatory systems in mice: the cholinergic V0c interneurons in the spinal cord and the serotonergic system in the brainstem. Electromyographic and behavioral recordings revealed that, when compared to control mice, mice whose V0c interneuron cholinergic output was genetically inactivated failed to display speed-dependent modulation of the gastrocnemius muscle, and exhibited lower amplitude bursting in the gastrocnemius muscle during swimming. c-Fos expression in this population during locomotion also indicated that they are active in a speed-dependent manner. Relative to control mice, those mice whose V0c interneurons had their cholinergic output inactivated showed upregulated activity in motor-related serotonergic populations while trotting at higher speeds but not while walking at lower speeds, indicating that serotonin plays a compensatory role in the absence of functional V0c interneurons. Last, we observed a progressive recruitment of these two populations in mice with amyotrophic lateral sclerosis, and the recruitment of serotonergic neurons is hastened in those mice whose V0c interneurons had their cholinergic output inactivated. These findings highlight that modulatory systems scale their activity to match motor demand across various circumstances.},
}

Animals
Mice
*Motor Neurons/physiology/metabolism
*Interneurons/physiology/metabolism
Spinal Cord/physiology/metabolism
Serotonin/metabolism
Brain Stem/physiology/metabolism
Muscle, Skeletal/physiology
Locomotion/physiology
Cholinergic Neurons/physiology/metabolism
Male
Electromyography

@article {pmid41642483,
year = {2026},
author = {Alhajeri, MM and Abukhaled, Y and Alkhanjari, RR and Bassiouni, W and Al-Ali, H and Baig, A and Sembaij, SH and Al Muhairi, FA and Dimassi, Z and Hamdan, H and Abd-Elrahman, KS},
title = {Neuroglial Function and Hormonal Modulation in Neurodegenerative Diseases: The Influence of Sex Hormones.},
journal = {Cellular and molecular neurobiology},
volume = {},
number = {},
pages = {},
doi = {10.1007/s10571-026-01674-1},
pmid = {41642483},
issn = {1573-6830},
abstract = {Astrocytes, microglia, and oligodendrocytes, key neuroglial cell types, are essential for central nervous system (CNS) homeostasis, immune regulation, and neuronal support. In neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), glial dysfunction contributes to pathogenesis via chronic inflammation, synaptic disruption, oxidative stress, and impaired myelination. Growing evidence highlights the regulatory influence of sex hormones on glial function. These hormones modulate inflammatory tone, synaptic remodeling, and remyelination, potentially contributing to sex-based differences in disease incidence, progression, and treatment response. This review synthesizes current understanding of glial involvement in neurodegeneration and examines how gonadal hormones interact with astrocytes, microglia, and oligodendrocytes. By integrating glial biology with neuroendocrinology, we propose that hormone-glia interactions represent promising, personalized targets for sex-informed therapies in CNS disorders.},
}

@article {pmid41642424,
year = {2026},
author = {Sun, Y and Huang, C and Pan, Y and Zhang, H and He, X},
title = {Correction: Muscle Fibrosis in Amyotrophic Lateral Sclerosis: Molecular Mechanisms, Diagnostic Advances, and Therapeutic Strategies.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {418},
doi = {10.1007/s12035-026-05721-2},
pmid = {41642424},
issn = {1559-1182},
}

@article {pmid41641857,
year = {2026},
author = {Marcinkowska, K and Wrzesińska-Krupa, B and Obrępalska-Stęplowska, A},
title = {Insights Into Sequences of Viral and Bacterial Origin in the Metatranscriptome of Centaurea cyanus L. Susceptible and Resistant to Acetolactate Synthase (ALS)-Inhibiting Herbicides.},
journal = {Environmental microbiology reports},
volume = {18},
number = {1},
pages = {e70287},
doi = {10.1111/1758-2229.70287},
pmid = {41641857},
issn = {1758-2229},
support = {2020/04/X/NZ9/01767//National Science Centre/ ; },
mesh = {*Herbicides/pharmacology ; *Acetolactate Synthase/antagonists & inhibitors ; *Bacteria/genetics/classification/isolation & purification/drug effects ; *Herbicide Resistance ; *Centaurea/microbiology/virology ; Arylsulfonates/pharmacology ; Transcriptome ; Poland ; Plant Weeds/virology/microbiology ; *Plant Viruses/genetics/classification/isolation & purification ; Phylogeny ; },
abstract = {Cornflower (Centaurea cyanus L.) is a widespread weed in cereal crops and is commonly controlled with sulfonylurea herbicides. In Poland, populations of cornflower resistant to acetolactate synthase inhibiting herbicides, such as tribenuron-methyl, have been increasingly reported. Both target-site and non-target-site resistance mechanisms may contribute to this phenomenon. Plant-associated microorganisms are known to play essential roles in alleviating abiotic stress. Moreover, weeds are considered reservoirs of plant pathogenic viruses. Since bacteria and viruses associated with cornflower have not been analysed to date, data mining was undertaken to identify viral and bacterial sequences in metatranscriptome datasets obtained from plant biotypes that are both susceptible and highly resistant to tribenuron-methyl. Using MEGAN6 and Kraken2, taxonomic classification revealed the presence of sequences of two double-stranded RNA viruses belonging to the family Partitiviridae, which have not been described before. For bacterial sequences, 19 genera were identified, including Bacillus, Mesorhizobium and Acinetobacter, some of which are associated with plant growth promotion or xenobiotic degradation. Although the presence of partitiviruses was unrelated to herbicide resistance status, some bacterial genera (e.g., Rothia) were more abundant in resistant than in susceptible plants. These results suggest that those bacterial genera present in weeds may be involved in counteracting ALS-inhibiting herbicides.},
}

*Herbicides/pharmacology
*Acetolactate Synthase/antagonists & inhibitors
*Bacteria/genetics/classification/isolation & purification/drug effects
*Herbicide Resistance
*Centaurea/microbiology/virology
Arylsulfonates/pharmacology
Transcriptome
Poland
Plant Weeds/virology/microbiology
*Plant Viruses/genetics/classification/isolation & purification
Phylogeny

@article {pmid41641779,
year = {2026},
author = {Varderidou-Minasian, S and Jakobs, CE and Pasteuning-Vuhman, S and Gal, L and Timmers, A and Altelaar, M and Lorenowicz, MJ and Pasterkamp, RJ},
title = {Mesenchymal stem cell-derived extracellular vesicle treatment of induced pluripotent stem cell-derived motor neurons with different amyotrophic lateral sclerosis genetic backgrounds.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-01790},
pmid = {41641779},
issn = {1673-5374},
abstract = {Motor neurons derived from induced human pluripotent stem cells offer a powerful model to study motor neuron diseases, such as amyotrophic lateral sclerosis. While widely used, our knowledge of the proteomic changes in these models is rather rudimentary. In this study, we conducted a comparative proteomic analysis of induced pluripotent stem cell-derived motor neurons carrying amyotrophic lateral sclerosis-associated mutations in C9ORF72, TARDBP, or FUS. This revealed both mutation-specific and shared proteomic signatures, unveiling common and divergent disease mechanisms. Using these new insights, we then evaluated the therapeutic potential of mesenchymal stem cell-derived extracellular vesicles. These experiments showed a functional effect of mesenchymal stem cell-derived extracellular vesicles in amyotrophic lateral sclerosis-FUS motor neurons in vitro and their ability to reverse proteomic changes more generally in motor neurons with different amyotrophic lateral sclerosis genetic backgrounds. These findings highlight key molecular pathways involved in amyotrophic lateral sclerosis at the protein level and support the potential of mesenchymal stem cell-derived extracellular vesicles as a versatile therapeutic approach.},
}

@article {pmid41641215,
year = {2026},
author = {Zhang, Y and Wang, JJ and Xing, HY and Yan, J},
title = {Neurofeedback for autism spectrum disorder: Current evidence, challenges, and future directions.},
journal = {World journal of psychiatry},
volume = {16},
number = {2},
pages = {114358},
pmid = {41641215},
issn = {2220-3206},
abstract = {Neurofeedback therapy (NFT) has emerged as a promising noninvasive intervention for autism spectrum disorder (ASD), targeting core symptoms such as social communication deficits and emotional dysregulation. This editorial synthesizes findings from recent studies, including Wang et al's retrospective analysis (2025), which reported improvements in Social Responsiveness Scale and Aberrant Behavior Checklist scores following NFT combined with conventional therapy. Mechanistically, NFT may modulate prefrontal gamma-band activity, enhances neuroplasticity in social brain networks (e.g., default mode network, a brain network involved in social cognition), and optimizes cognitive processing via event-related potential changes (e.g., shortened P300 latency). Emerging trends include hybrid approaches (e.g., NFT with repetitive transcranial magnetic stimulation and artificial intelligence-driven protocols). However, challenges persist in protocol standardization, long-term efficacy validation, and biomarker identification. Future research must prioritize large-scale randomized trials, neuromarker discovery, and individualized protocols to establish NFT as a viable component of precision psychiatry for ASD.},
}

@article {pmid41640951,
year = {2026},
author = {Cui, X and Yin, BQ and Chen, L},
title = {Remote telerehabilitation for frailty management in liver transplant candidates: A feasible yet underutilized strategy.},
journal = {World journal of hepatology},
volume = {18},
number = {1},
pages = {114880},
pmid = {41640951},
issn = {1948-5182},
abstract = {This letter reviews Loschi et al's study evaluating structured telerehabilitation for frail cirrhotic liver transplant candidates, which fills a critical pre-transplant care gap. The video-based program, using low-cost tools and asynchronous sessions, improved liver frailty index reduction and function in adherent patients (29.8%) although a high attrition rate (70%) highlighted engagement challenges. Limitations include a small, non-randomized sample, mixed frailty subgroups, and unexplored long-term effects. Future directions emphasize hybrid models, patient-centered barrier analysis, and policy-driven frailty screening. This work advances digital health for cirrhosis; however, larger trials are needed to optimize outcomes.},
}

@article {pmid41640615,
year = {2026},
author = {Wang, G and Pan, SJ},
title = {Integrative acupoint stimulation within enhanced recovery after endoscopic procedures: Harnessing the neuroimmune axis for enhanced gastrointestinal recovery.},
journal = {World journal of gastroenterology},
volume = {32},
number = {3},
pages = {114048},
pmid = {41640615},
issn = {2219-2840},
mesh = {Humans ; *Acupuncture Points ; Recovery of Function ; *Enhanced Recovery After Surgery ; *Gastrointestinal Tract/innervation/surgery/immunology ; Neuroimmunomodulation ; Randomized Controlled Trials as Topic ; *Perioperative Care/methods ; Hypothalamo-Hypophyseal System/immunology ; *Transcutaneous Electric Nerve Stimulation/methods ; Pituitary-Adrenal System ; *Endoscopy, Gastrointestinal/adverse effects ; Treatment Outcome ; },
abstract = {Enhanced recovery after surgery (ERAS) programs have transformed perioperative care, yet delayed gastrointestinal function and excessive neuroendocrine stress remain major obstacles to optimal recovery. Hong et al's randomized controlled trial embedded acupoint-based neuromodulation - meridian-timed acupoint application combined with transcutaneous electrical acupoint stimulation - within an ERAS framework and demonstrated accelerated gastrointestinal recovery accompanied by endocrine attenuation. This article offers a structured critical appraisal of the trial, emphasizing methodological rigor, mechanistic plausibility, and alignment with ERAS core principles of stress mitigation, functional restoration, and patient experience. The observed reductions in norepinephrine, cortisol, and aldosterone suggest modulation of the hypothalamic-pituitary-adrenal axis as a key mediator of benefit. Future research priorities include multicenter, sham-controlled validation; integration of autonomic and inflammatory biomarkers (heart rate variability, interleukin-6, tumor necrosis factor-α, C-reactive protein); and pragmatic evaluation of cost-effectiveness and acceptability. Positioning acupoint stimulation within precision-integrative perioperative care could advance ERAS from a recovery protocol to a system of host-response modulation. Integrative acupoint neuromodulation thus represents a biologically coherent, low-risk, and scalable strategy for enhancing resilience, accelerating gastrointestinal recovery, and improving surgical outcomes worldwide.},
}

Humans
*Acupuncture Points
Recovery of Function
*Enhanced Recovery After Surgery
*Gastrointestinal Tract/innervation/surgery/immunology
Neuroimmunomodulation
Randomized Controlled Trials as Topic
*Perioperative Care/methods
Hypothalamo-Hypophyseal System/immunology
*Transcutaneous Electric Nerve Stimulation/methods
Pituitary-Adrenal System
*Endoscopy, Gastrointestinal/adverse effects
Treatment Outcome

@article {pmid41640493,
year = {2025},
author = {Li, SC},
title = {Evolving target: A 16-year progressive framework for shifting the rubric of scientific publishing toward transparency, artificial intelligence, and the Economic Impact Factor for impact that matters.},
journal = {World journal of stem cells},
volume = {17},
number = {12},
pages = {111748},
pmid = {41640493},
issn = {1948-0210},
abstract = {Reflecting on 16 years of continuous evolution at the World Journal of Stem Cells, this editorial offers a forward-looking vision for redefining the framework of scientific publishing. With the emergence of artificial intelligence, open science, and the growing need for translational value, we propose shifting from traditional citation-based assessments toward an impact and progress framework, anchored by the Economic Impact Factor. The World Journal of Stem Cells experience, grounded in metrics and milestones, supports this evolution: Among the more than 1200 published articles since inception, our top 10 cited works have collectively accrued over 2475 citations, led by Kyurkchiev et al (398 citations) and Casteilla et al (392 citations). Emerging scholars such as Ann De Becker and Nipha Chaicharoenaudomrung have shaped the next generation of research, as seen in our top 10 junior authors table. Clinically, World Journal of Stem Cells has supported critical translational work, such as Tsang et al's mesenchymal stem cell stroke trial (27 citations), illustrating real-world impact. Thematic breadth remains a cornerstone, with 22 focus areas including artificial intelligence-integrated programming, spatial single-cell biology, CRISPR-based gene editing, and bench-to-bedside translation. As Nature and other leading publishers move toward transparent peer review, World Journal of Stem Cells embraces editorial co-creation, recognizing peer reviewers and editors as contributors with "10000-foot eagle views" by publishing peer-review reports side-by-side with the related manuscripts since its inception. Together, these shifts signify a call to recalibrate what we value in science - not just what is cited, but what truly counts.},
}

@article {pmid41640104,
year = {2026},
author = {Karros, M and DiFulco, M and Nogid, A},
title = {Tofersen: A Novel Option for the Treatment of Amyotrophic Lateral Sclerosis.},
journal = {The Annals of pharmacotherapy},
volume = {},
number = {},
pages = {10600280251408862},
doi = {10.1177/10600280251408862},
pmid = {41640104},
issn = {1542-6270},
abstract = {OBJECTIVE: This review summarizes current evidence on the efficacy and safety of tofersen (Qalsody) in treating amyotrophic lateral sclerosis (ALS).

DATA SOURCES: PubMed, MEDLINE, Google Scholar, and ClinicalTrials.gov were searched using the keywords: Qalsody, BIIB067, antisense oligonucleotides, SOD1, and amyotrophic lateral sclerosis. Articles published from inception to November 2025 were included.

English-language studies assessing the pharmacokinetics, pharmacology, efficacy, and safety of tofersen were included. Prescribing information and real-world evidence were also reviewed.

DATA SYNTHESIS: Tofersen is an intrathecally administered antisense oligonucleotide targeting superoxide dismutase 1 (SOD1) mRNA. Early trials demonstrate dose-dependent reductions in cerebrospinal fluid (CSF) SOD1 protein levels of -33% and slower ALS Functional Rating Scale (ALSFRS-R) decline compared to placebo (-1.19 vs -5.63 points). In Phase 3 trials, tofersen reduced CSF SOD1 by 29% and plasma neurofilament light chain (NfL) by 60%, while biomarkers increased in the placebo group. There was no significant difference in ALSFRS-R decline between tofersen and placebo (-6.98 vs -8.14; P = 0.97). Real-world data show favorable patient-related outcomes and improvement in ALSFRS-R. Adverse effects are primarily lumbar puncture related with serious neurologic events documented in 7% of tofersen recipients.Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs:As the first Food and Drug Administration (FDA)-approved gene-directed therapy for SOD1 ALS, tofersen directly targets the underlying genetic cause. Barriers include the need for genetic confirmation and intrathecal administration.

CONCLUSION: Tofersen provides a promising targeted treatment option for pathogenic SOD1 ALS. Ongoing studies will clarify its long-term clinical impact.},
}

@article {pmid41640102,
year = {2026},
author = {Ross, D and Lewis, O and McLean, O and Bhanot, S and Donahue, S and Baker, R and Dias, R and Eagerton, D and Mohanty, V and Mohanty, BK},
title = {Thermally activated history-dependent homogenization of G-quadruplexes in an ALS/FTD-associated gene.},
journal = {Biophysical journal},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.bpj.2026.01.054},
pmid = {41640102},
issn = {1542-0086},
abstract = {A significant proportion of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) cases exhibit a substantial copy number expansion of the hexanucleotide GGGGCC/GGCCCC sequence in the C9ORF72 gene. The GGGGCC sequence forms a non-canonical DNA structure called a G-quadruplex (G4) which has been associated with the disease states and with nucleic acid condensate formation. G4s can fold into various topologies, which can differentially impact fidelity of DNA synthesis. However, how G4 conformational heterogeneity and its regulation impact hexanucleotide repeat expansion is unclear, and important clues may lie in the thermodynamic properties of different G4 topologies. Here, we use temperature-swept CD spectroscopy to observe configurational homogenization of an initially heterogeneous population of G4s over a small range of temperatures, demonstrating thermally activated behavior. The G4s adopt the parallel configuration after the temperature sweep, and subsequent temperature sweeps show little to no reversal back to non-parallel topologies, suggesting the homogenization is history-dependent. Finally, we provide an analytical theory based on a two-state thermodynamic model which is compatible with experimental evidence, and we discuss alternate mechanisms for the homogenization transition. These findings suggest that kinetic regulation of non-canonical DNA structures may play a role in cellular homeostasis or disease pathogenesis.},
}

@article {pmid41639687,
year = {2026},
author = {Zhang, N and Su, WM and Chen, T and Zhang, Q and Cao, B and Wang, Y and Chen, YP},
title = {From pathogenesis to therapy: the emerging role of regulatory T cells in amyotrophic lateral sclerosis.},
journal = {Journal of neuroinflammation},
volume = {23},
number = {1},
pages = {50},
pmid = {41639687},
issn = {1742-2094},
support = {82371422//National Natural Science Fund of China/ ; 2022YFC2703101//National Key Research and Development Program of China/ ; 2023HXFH032//1·3·5 project for disciplines of excellence Clinical Research Fund, West China Hospital, Sichuan University/ ; },
}

@article {pmid41639347,
year = {2026},
author = {Tosi, M and Favero, F and Zuccalà, M and Visha, E and Caushi, F and Barizzone, N and Pomella, N and Follia, L and Corrado, L and Corà, D and Martignetti, L and Leone, M and D'Alfonso, S},
title = {A multi-omics study on monozygotic twins discordant for amyotrophic lateral sclerosis and literature review underline a potential role for innate immunity and epigenetic dysregulation in disease mechanisms.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {3},
pages = {230},
pmid = {41639347},
issn = {1590-3478},
support = {DIG-ALS//AriSLA/ ; PRIN project GENIALS//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by motor neuron degeneration. Although genetic contributions to both familial and sporadic ALS (sALS) cases are well established, a substantial portion of ALS heritability remains unexplained, suggesting the involvement of other genetic and epigenetic factors.

METHODS: To address this gap, we have devised a comprehensive multi-omics approach in a pair of Italian monozygotic twins discordant for ALS, performing DNA methylation, transcriptomic, and whole exome sequencing (WES). We then conducted a structured literature research on ALS-discordant monozygotic twins (n = 45) and on case-control sALS (~ 7000 patients and ~ 3000 controls), investigated for at least one of the omics approaches.

RESULTS: Our exploratory analysis reveals distinct transcriptomic and epigenetic profiles underlying the discordant disease phenotypes in genetically identical individuals, particularly implicating immune system functions and brain development pathways. Notably, a comprehensive comparison of our results with existing literature underlined the involvement of pathways related to NK cell activation, chemokine production, and signal transduction, suggesting potential shared disease associated mechanisms across ALS cases.

CONCLUSIONS: This hypothesis-generating study, although limited by the sample size, demonstrates the utility of multi-omics approaches in uncovering broader pathological insights into ALS, speculating on the possible contribution of innate immunity and epigenetic dysregulation in disease processes. This work provides a foundation for future research aimed at identifying disease-associated processes and biomarkers.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10072-026-08813-y.},
}

@article {pmid41639245,
year = {2026},
author = {Fernandes, AR and Owen, AP and Faroqi, AH and Lee, J and Sachdeva, GS and Morderer, D and Hoffmann, C and Madden, B and Zhang, S and Ren, Y and Boschen, SL and Pandey, A and Rossoll, W and McLean, PJ},
title = {A split biotin ligase approach reveals proteins associated with oligomeric alpha-synuclein during aggregation.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-37551-6},
pmid = {41639245},
issn = {2045-2322},
support = {U01CA271410/BC/NCI NIH HHS/United States ; RF1AG076122/GF/NIH HHS/United States ; A2021615S//BrightFocus Foundation/ ; 23A04//Florida Department of Health Ed and Ethel Moore Alzheimer's Disease Research Grant/ ; 024079//Michael J. Fox Foundation for Parkinson's Research/ ; 24A10//Florida Department of Health Ed and Ethel Moore AD Research Program/ ; U54 NS110435/NS/NINDS NIH HHS/United States ; APDA#11-08//Mayo Clinic American Parkinson's Disease Association Center for Advanced Research/ ; },
abstract = {Lewy pathology can form over decades in patients with Lewy body diseases, but the causal cellular mechanisms associated with this process remain unclear. This project aims to discover proteins that associate with monomeric and/or oligomeric alpha-synuclein during early stages of the aggregation process. To mimic aggregation processes, cells expressing a synuclein-biotin ligase fusion protein were treated with human recombinant pre-formed fibrils and subjected to BioSITe and mass spectrometry. Using a novel split biotin ligase fused to alpha-synuclein facilitated the identification of proteins specifically associated with multimeric alpha-synuclein. A total of 581 proteins were differentiated into potential interactors of monomeric versus multimeric alpha-synuclein in physiological versus aggregated conditions. The data reveal potentially relevant phosphorylation mechanisms, connections to insulin processing, and a potential interaction with ALS/FTD-associated FUS. Interestingly, we propose that loss of specific interactions may contribute to pathology in patients with sporadic onset of Lewy body diseases. Future studies will validate both true interaction of highlighted proteins with alpha-synuclein, and the impact of such proteins on alpha-synuclein aggregation.},
}

@article {pmid41639167,
year = {2026},
author = {Jansén-Storbacka, LR and Honasoge, KS and Molnárová, E and Soboleva, A and Agema, BC and Paats, MS and Moes, DJAR and Veerman, GDM and Barbaro, ABT and Dobbe, R and Grossmann, I and Azimi, S and Mathijssen, RHJ and Dingemans, AC and Staňková, K},
title = {Can evolutionary therapy be applied in non-small cell lung cancer?.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-36712-x},
pmid = {41639167},
issn = {2045-2322},
support = {VI.Vidi.213.139//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 955708//European Commission/ ; },
abstract = {Evolutionary therapy (ET) applies principles of evolutionary biology to steer tumour dynamics and forestall or delay treatment resistance, typically guided by data-driven mathematical models. Our aim is to assess whether ET protocols, and specifically Zhang et al.'s protocol proposed for metastatic castrate-resistant prostate cancer, can be theoretically effective for fast-growing metastatic cancers such as stage IV non-small-cell lung cancer (NSCLC). Using longitudinal tumour-burden data from NSCLC patients treated with erlotinib, we systematically evaluate 26 two-population differential-equation models based on classical tumour-growth dynamics, with varying assumptions about density- and frequency-dependent interactions, pharmacokinetics, and treatment-induced death. Previous work by Yin et al. on the same dataset employed an exponential model that omitted density- and frequency-dependent interactions; although it provided a good fit to tumour-burden data, its structure would theoretically lead to poorer outcomes under ET protocols. In contrast, our analysis identifies the minimal model structure required to reproduce the resistance-driven regrowth observed in NSCLC, with the Gompertzian model featuring log-kill dynamics and both density- and frequency-dependent interactions providing the best fit. In this model, Zhang et al.'s protocol prolonged median time-to-progression to 42.3 months compared with 24.8 months under maximum tolerated dose. These results indicate that ET is theoretically a viable treatment strategy for NSCLC. This study offers a practical framework for assessing ET feasibility using clinical data and supports future clinical translation of ET in NSCLC.},
}

@article {pmid41638908,
year = {2026},
author = {Villarroel-Campos, D and Vargas, JNS and Wallace, M and Sun, K and Sleigh, JN and Fratta, P and Schiavo, G},
title = {TBK1 activity regulates the directionality of axonal transport of signalling endosomes.},
journal = {Life science alliance},
volume = {9},
number = {4},
pages = {},
pmid = {41638908},
issn = {2575-1077},
mesh = {*Protein Serine-Threonine Kinases/metabolism/genetics ; *Endosomes/metabolism ; *Axonal Transport/physiology ; Humans ; Signal Transduction ; Phosphorylation ; Animals ; rab GTP-Binding Proteins/metabolism/genetics ; rab7 GTP-Binding Proteins ; Amyotrophic Lateral Sclerosis/metabolism ; Mice ; Axons/metabolism ; Motor Neurons/metabolism ; Lysosomes/metabolism ; Protein Transport ; Neurons/metabolism ; },
abstract = {The polarised and complex morphology of neurons poses massive challenges for efficient cargo delivery between the axon and soma, a process termed axonal transport. We have previously shown that the retrograde axonal transport of pro-survival, neurotrophic signalling endosomes relies on Rab7 in motor neurons, and that their trafficking is impaired in the early stages of amyotrophic lateral sclerosis (ALS) pathogenesis. Here, we report the effect of Rab7 phosphorylation on the transport of these signalling endosomes. We show that the ALS-linked kinase TBK1 phosphorylates Rab7 at S72 in neurons, altering its binding to cytoplasmic dynein adaptors. Accordingly, both TBK1 knockdown and the expression of a loss-of-function Rab7 mutant (S72E) induce aberrant bidirectional movement of signalling endosomes without modifying neuronal polarity or endosomal sorting. This alteration is specific for signalling endosomes, as axonal transport of lysosomes and mitochondria remains unaffected. We have therefore discovered a new TBK1 function that ensures the unidirectional transport of signalling endosomes, suggesting that reduced TBK1 activity determines retrograde transport dysfunctions and long-range signalling impairments.},
}

*Protein Serine-Threonine Kinases/metabolism/genetics
*Endosomes/metabolism
*Axonal Transport/physiology
Humans
Signal Transduction
Phosphorylation
Animals
rab GTP-Binding Proteins/metabolism/genetics
rab7 GTP-Binding Proteins
Amyotrophic Lateral Sclerosis/metabolism
Mice
Axons/metabolism
Motor Neurons/metabolism
Lysosomes/metabolism
Protein Transport
Neurons/metabolism

@article {pmid41638429,
year = {2026},
author = {Madsen, M and Rønne, ME and Petersen, AB and Tandrup, T and Pilgaard, B and Holck, J and Aachmann, FL and Wilkens, C and Klau, LJ and Svensson, B},
title = {Dissecting a two-domain alginate lyase of family PL6 reveals a mechanistic basis for substrate specificity and enzyme activity.},
journal = {The Journal of biological chemistry},
volume = {},
number = {},
pages = {111227},
doi = {10.1016/j.jbc.2026.111227},
pmid = {41638429},
issn = {1083-351X},
abstract = {Alginate lyases (ALs) cleave 4-O-glycosidic linkages in alginate, composed of mannuronate (M) and guluronate (G) residues via β-elimination with preference for either one or several M-M, M-G, G-M, G-G linkages. ALs in polysaccharide lyase family 6 (PL6), present different specificities and modes of action, contain either one or two parallel β-helix domains. About half of almost 600 PL6 sequences are of the two-domain type, all located in the phyla Pseudomonadota and Bacteroidota. Here, functional roles are described for the N- and C-terminal domains (NTD and CTD) using BoPL6, a two-domain AL from the human gut bacterium Bacteroides ovatus CP926, which is specific for G in subsite +1. The NTD contains the catalytic site, but BoPL6-NTD markedly preferred the model substrate polyMG and cleaved M-G bonds in endo-mode, whereas the NTD + CTD mixture, similarly to BoPL6, acted with highest activity on model substrate polyG in exo-mode, verified by time-resolved [1]H-NMR. CTD was not catalytically active but bound polyguluronate and, when mixed with BoPL6-NTD, promoted activity on polyG, yielding products of DP 1‒3, similarly to BoPL6. This defines a crucial role of CTD in shaping the active site in BoPL6, as validated by substrate docking. The BoPL6 E634A mutant in the conserved CTD DEST loop, interacting with the active site in two-domain PL6 enzymes, was inactive, while the corresponding CTD mutant mixed with the NTD did not form the WT structure and had highly reduced activity on polyG, but acted on polyMG in endo-mode with improved rate and conversion.},
}

@article {pmid41638255,
year = {2026},
author = {Yeh, CH and Chen, SC},
title = {Comments on Huang et al.'s "Proteomic profiling reveals distinct inflammatory and neurogenic endotypes in rosacea".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2025.12.114},
pmid = {41638255},
issn = {1097-6787},
}

@article {pmid41637622,
year = {2026},
author = {Du, C and Li, Y and Wu, R and Shen, Y and Yang, J and Xiao, X and Zhou, Y},
title = {Aberrant Splicing Signatures Underpin Oligodendrocyte Damage in ALS and Neuron Loss in FTD.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e14886},
doi = {10.1002/advs.202514886},
pmid = {41637622},
issn = {2198-3844},
support = {2023YFC2307802//National Key R&D Program of China/ ; 2042022dx0003//Fundamental Research Funds for the Central Universities/ ; 2025AFA051//Hubei Provincial Natural Science Foundation of China/ ; 2023AFB182//Hubei Provincial Natural Science Foundation of China/ ; 2023KFZZ007//Open Project of Hubei Key Laboratory/ ; 32525018//National Natural Science Foundation of China/ ; 82341023//National Natural Science Foundation of China/ ; 324B2009//National Natural Science Foundation of China/ ; 82401650//National Natural Science Foundation of China/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two severe diseases sharing similar genetic, pathological, and clinical features, including TDP-43 pathology. However, differences in molecular changes between ALS and FTD remain elusive. Here, integrating large sets of bulk and single-nucleus RNA-seq from ALS/FTD patients revealed expression and splicing changes indicating more severe oligodendrocyte damage in ALS than FTD, and more significant neuron loss in FTD. Specifically, we identified 31 oligodendrocyte-specific and 507 neuron-specific aberrant splicing junctions as potential biomarkers with robust classification performance, and experimentally validated a novel target in patient tissues. Moreover, we found that abnormally spliced transcripts produced de novo peptides in patients' cerebrospinal fluids. Importantly, we further identified the targets of TDP-43 in glial cells and decoded the differential RNA-binding protein (RBP) contexts of TDP-43-regulated aberrant splicing. These findings uncover that ALS and FTD patients have distinct dysfunctional cell populations harboring specific aberrant splicing signatures, suggesting varying cellular impacts and providing potential biomarkers and insights into molecular mechanisms underlying ALS/FTD.},
}

@article {pmid41635876,
year = {2025},
author = {Elsawah, HK and Elmarawany, MN},
title = {Letter regarding Pereira et al.'s SAH-VP score: Methodological and statistical considerations.},
journal = {Brain & spine},
volume = {5},
number = {},
pages = {104294},
pmid = {41635876},
issn = {2772-5294},
}

@article {pmid41635251,
year = {2026},
author = {Li, X and Ding, W and Lu, Y and Sun, M and Xu, E},
title = {Nocturnal Hypoxia and Sleep-Disordered Breathing as Potential Early Biomarkers of Respiratory Progression in Mild ALS.},
journal = {The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques},
volume = {},
number = {},
pages = {1-20},
doi = {10.1017/cjn.2026.10557},
pmid = {41635251},
issn = {0317-1671},
}

@article {pmid41635249,
year = {2026},
author = {Ponikiewska, K and Strus, W and Cieciuch, J},
title = {The Temperament Metadimensions Model: A Complex Framework for Formal Characteristics of Behavior as Composed of Energetic, Temporal, and Autoregulatory Facets of Reactivity and Activity.},
journal = {Journal of personality},
volume = {},
number = {},
pages = {},
doi = {10.1111/jopy.70054},
pmid = {41635249},
issn = {1467-6494},
abstract = {OBJECTIVE: The paper presents the Temperament Metadimensions Model (TMM), which extends the integrative model of temperament structure proposed by Strus et al. (2022). This extension adds four autoregulatory trait-facets to the originally proposed four energetic and four temporal ones, enhancing the theoretical comprehensiveness of the model in terms of regulatory function of temperament and coverage of crucial constructs postulated in other well-established temperament theories. The autoregulatory trait-facets were conceptually introduced and subsequently empirically tested within the whole expanded 12 trait-facet model of bipolar and orthogonal Reactivity and Activity metadimensions, verifying its synthesizing and predictive potential.

METHOD: The empirical verification of the TMM model was performed throughout three subsequent studies, with a joint sample of 1756 participants (52.0% females; Mage = 34.68). We examined the TMM's: (1) internal structure, (2) relationships with constructs from other established theories of temperament, and (3) predictive capabilities in relation to mental health-related variables.

RESULTS AND CONCLUSIONS: The obtained results confirmed the validity of the 12-facet TMM as an integrative and comprehensive framework for formal characteristics of behavior, possessing evident functional significance and indicating its superiority over the eight-facet Strus et al.'s (2022) model. Theoretical implications of the TMM were discussed.},
}

@article {pmid41635116,
year = {2026},
author = {Wang, Y and Lipton, SA},
title = {Aberrant Protein S-Nitrosylation Mimics the Effect of Rare Genetic Mutations in Neurodegenerative Diseases.},
journal = {Journal of neurochemistry},
volume = {170},
number = {2},
pages = {e70365},
doi = {10.1111/jnc.70365},
pmid = {41635116},
issn = {1471-4159},
support = {DP1 DA041722/DA/NIDA NIH HHS/United States ; R01 DA048882/DA/NIDA NIH HHS/United States ; ReMIND-L DISC4 16292//California Institute for Regenerative Medicine/ ; R01 AG056259/AG/NIA NIH HHS/United States ; R01 AG078756/AG/NIA NIH HHS/United States ; R35 AG071734/AG/NIA NIH HHS/United States ; R56 AG065372/AG/NIA NIH HHS/United States ; RF1 AG057409/AG/NIA NIH HHS/United States ; U01 AG088679/AG/NIA NIH HHS/United States ; /NH/NIH HHS/United States ; /NH/NIH HHS/United States ; },
mesh = {Humans ; *Neurodegenerative Diseases/genetics/metabolism ; Animals ; *Mutation/genetics ; *Protein Processing, Post-Translational/genetics ; },
abstract = {Neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease/Lewy body dementia (PD/LBD), and amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) are driven by complex interactions of genetic and environmental factors. While genome wide association studies (GWAS) have uncovered a number of risk gene variants (e.g., APOE, SNCA [encoding α-synuclein], and protein disulfide isomerase [PDI]), these genetic factors alone cannot fully explain disease onset or progression. Emerging evidence suggests that post-translational modifications of proteins, particularly S-nitrosylation (SNO), act as a critical link between environmental stress and neurodegenerative pathology. Here, we review data showing that while physiological protein SNO regulates diverse neuronal processes, aberrant SNO, occurring very commonly in the diseased brain, can disrupt protein function in ways that mimic the deleterious effects of rare genetic mutations. We advance the concept of "mutational mimicry," whereby aberrant SNO of key neuronal or glial proteins reproduces the functional consequences of known specific genetic mutations, ultimately converging on common pathways of synaptic dysfunction emanating from mitochondrial and metabolic impairment, proteostasis, neuroinflammation, and so on. Supporting this framework, proteomic analyses show significant overlap between abnormally S-nitrosylated proteins in diseased brains and known genetic risk factors in AD and PD/LBD as well as in ALS. By linking redox biology to human genetics, this review highlights how environmental factors can phenocopy or enhance genetic susceptibilities. Understanding this convergence not only provides novel insight into disease mechanisms but also suggests new therapeutic targets to intervene in these convergent pathways with the goal of halting neurodegenerative processes.},
}

Humans
*Neurodegenerative Diseases/genetics/metabolism
Animals
*Mutation/genetics
*Protein Processing, Post-Translational/genetics

@article {pmid41634873,
year = {2026},
author = {Garrigos, D and Martinez-Morga, M and Pombero, A and García-Lopez, R and Pastor, D and Riquelme, D and Blanquer, M and Iniesta, F and Valdor, R and Geijo-Barrientos, E and Hargus, G and Moraleda, JM and Martínez, S},
title = {Chaperone mediated autophagy is deficient in spinal motoneurons of ALS patients with TDP-43 proteinopathy.},
journal = {Acta neuropathologica communications},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40478-026-02238-6},
pmid = {41634873},
issn = {2051-5960},
support = {Grant Numbers SEV-2017-0723//Spanish State Research Agency, through the "Severo Ochoa" Programme for Centres of Excellence in R&D/ ; Grant Numbers SEV-2017-0723//Spanish State Research Agency, through the "Severo Ochoa" Programme for Centres of Excellence in R&D/ ; Grant Numbers SEV-2017-0723//Spanish State Research Agency, through the "Severo Ochoa" Programme for Centres of Excellence in R&D/ ; Grant Numbers SEV-2017-0723//Spanish State Research Agency, through the "Severo Ochoa" Programme for Centres of Excellence in R&D/ ; Grant Numbers SEV-2017-0723//Spanish State Research Agency, through the "Severo Ochoa" Programme for Centres of Excellence in R&D/ ; Grant Numbers SEV-2017-0723//Spanish State Research Agency, through the "Severo Ochoa" Programme for Centres of Excellence in R&D/ ; Grant Numbers SEV-2017-0723//Spanish State Research Agency, through the "Severo Ochoa" Programme for Centres of Excellence in R&D/ ; SAF2017-83702-R and PID2020-11817RB-I00//Spanish Ministerio de Ciencia e Innovación/ ; SAF2017-83702-R and PID2020-11817RB-I00//Spanish Ministerio de Ciencia e Innovación/ ; SAF2017-83702-R and PID2020-11817RB-I00//Spanish Ministerio de Ciencia e Innovación/ ; SAF2017-83702-R and PID2020-11817RB-I00//Spanish Ministerio de Ciencia e Innovación/ ; SAF2017-83702-R and PID2020-11817RB-I00//Spanish Ministerio de Ciencia e Innovación/ ; SAF2017-83702-R and PID2020-11817RB-I00//Spanish Ministerio de Ciencia e Innovación/ ; SAF2017-83702-R and PID2020-11817RB-I00//Spanish Ministerio de Ciencia e Innovación/ ; SAF2017-83702-R and PID2020-11817RB-I00//Spanish Ministerio de Ciencia e Innovación/ ; Grant Number 2018/041//Generalitat Valenciana (program Prometeo II)/ ; Grant Number 2018/041//Generalitat Valenciana (program Prometeo II)/ ; Grant Number 2018/041//Generalitat Valenciana (program Prometeo II)/ ; Grant Number 2018/041//Generalitat Valenciana (program Prometeo II)/ ; Grant Number 2018/041//Generalitat Valenciana (program Prometeo II)/ ; Grant Number 2018/041//Generalitat Valenciana (program Prometeo II)/ ; Grant Number 2018/041//Generalitat Valenciana (program Prometeo II)/ ; RD21/0017/0017; RD21/0017/0001//Instituto de Salud Carlos III (ISCIII) through the RICORS Project TERAV/ ; RD21/0017/0017; RD21/0017/0001//Instituto de Salud Carlos III (ISCIII) through the RICORS Project TERAV/ ; RD21/0017/0017; RD21/0017/0001//Instituto de Salud Carlos III (ISCIII) through the RICORS Project TERAV/ ; RD21/0017/0017; RD21/0017/0001//Instituto de Salud Carlos III (ISCIII) through the RICORS Project TERAV/ ; RD21/0017/0017; RD21/0017/0001//Instituto de Salud Carlos III (ISCIII) through the RICORS Project TERAV/ ; Ramon y Cajal (RYC) 2019-027520-I//Ministerio de Ciencia e Innovación/ ; },
}

@article {pmid41633676,
year = {2025},
author = {Šoša, I and Sergi, CM},
title = {Genomics for Sudden Cardiac Death: A Review of the Topic and Call for Increased Professionalism in Clinico-Molecular Autopsy and Forensic Laboratory Sciences.},
journal = {Annals of clinical and laboratory science},
volume = {55},
number = {6},
pages = {859-868},
pmid = {41633676},
issn = {1550-8080},
mesh = {Humans ; *Death, Sudden, Cardiac/pathology ; *Genomics/methods ; Autopsy ; *Professionalism ; Gene Frequency ; *Forensic Genetics ; Genome, Human/genetics ; },
abstract = {In 2001, the first draft sequence of the human genome was released, the culmination of a decade-long, multibillion-dollar effort. Since then, an OMICs platform has been proposed to further evaluate and edit the human genome for diagnostic and therapeutic purposes. The Human Genome Project opened a Pandora's box, expanding the forensic laboratory physicians' toolbox. Kinship analysis has been used extensively for parentage testing and identifying cases of human remains and missing persons. The Combined DNA Index System has played a significant role in forensic DNA databases. Nanopore sequencing and improved genomic tools aid enormously in identifying amplicons from degraded samples. The application of genomics in determining the potential channelopathies of sudden cardiac death (SCD) has been an enormous step forward in recent years in forensic histopathology. We reviewed the literature. Kong et al.'s meta-analysis of the mean allele frequencies of SCN5A, NOS1AP, KCNH2, KCNE1, and KCNQ1 genes across Black, Caucasian, Asian, and Hispanic ethnicities has been pivotal to forensic science in the last decade. The authors used sequenced genomic data from the Exome Aggregation Consortium to compare allele frequencies between different ethnicities. They found that Asians had the highest overall mean allele frequencies for NOS1AP and SCN5A, Caucasians had the highest KCNH2 frequency, and Hispanics had the highest KCNQ1 frequency. In 2026, the call for increased professionalism in clinico-molecular autopsy and forensic laboratory sciences is driven by rapid technological advancements (e.g., forensic molecular genomic autopsies), critical workforce shortages in some geographical areas, and the increasing complexity of death investigations. This professionalization focuses on standardizing molecular protocols, enhancing ethical frameworks, and addressing the need for specialized interdisciplinary expertise.},
}

Humans
*Death, Sudden, Cardiac/pathology
*Genomics/methods
Autopsy
*Professionalism
Gene Frequency
*Forensic Genetics
Genome, Human/genetics

@article {pmid41633603,
year = {2026},
author = {Tian, X and Song, Z and Huang, Y and Yao, W},
title = {[Analysis of early complications and risk factors in patients with amyotrophic lateral sclerosis after percutaneous endoscopic gastrostomy].},
journal = {Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences},
volume = {58},
number = {1},
pages = {190-195},
pmid = {41633603},
issn = {1671-167X},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/surgery ; *Gastrostomy/adverse effects/methods ; Male ; Middle Aged ; Risk Factors ; Female ; Retrospective Studies ; *Postoperative Complications/etiology/epidemiology ; Aged ; Adult ; Enteral Nutrition/adverse effects/methods ; *Gastroscopy/adverse effects ; },
abstract = {OBJECTIVE: To explore risk factors of early complications (≤14 days) and the clinical characteristics in patients with amyotrophic lateral sclerosis (ALS) after percutaneous endoscopic gastrostomy (PEG).

METHODS: Patients diagnosed with ALS who underwent first PEG insertion between January 2011 and December 2020 were eligible. Medical records were retrospectively reviewed to determine clinical characteristics and outcomes (≤14 days) of patients who underwent the pull type PEG. Grouping was performed based on the presence and severity of complications, and SPSS 27.0 statistical software was used for data analysis. Finally, Logistic regression model was applied for multivariate factor analysis of risk factors related to complications.

RESULTS: In the study, 192 cases of PEG were all successfully completed, with 97 (51%) males, mean age of ALS onset disease (55±11) years and 93 (48%) bulbar onset symptoms included. Complications occurred in 40 (21%) cases after PEG within 14 days, all of which had fever, including 16 cases without clear infection focus, 18 cases of respiratory tract infections, and 6 cases of fistula site infections. In the study, 13 (7%) cases had major complications, including 11 cases of respiratory tract infection and 2 cases of stoma infection. Two cases of respiratory tract infection died due to respiratory failure, and the remaining 11 cases recovered after upgraded antibiotic. No complications, such as tube dislodgement, benign pneumoperitoneum, hemorrhage or buried bumper syndrome occurred. The operation time and postoperative hospital stay were longer in the complication group than in the non-complication group [(16±5) min vs. (13±5) min, P < 0.001; 6 (5, 9) d vs. 5 (3, 7) d, P=0.009]. Compared with the mild complication group, the creatinine and triglyceride in the major complication group were significantly lower [(46.5±16.2) μmol/L vs.(66.8±16.4) μmol/L, P＜0.001; (1.1±0.5) mmol/L vs.(1.6±0.7) mmol/L, P=0.038], and the operation time was significantly longer [(20±5) min vs. (15±5) min, P=0.002]. Further, Logistic regression model analysis revealed that the operation time was also independent associated with complications (OR=1.132, 95%CI: 1.051-1.220, P=0.001).

CONCLUSION: PEG was a reliable method for ALS patients to put nutrition tube. Postoperative fever was the most common complications. Long surgical duration was an independent risk factor for the occurrence of complications (≤14 d).},
}

Humans
*Amyotrophic Lateral Sclerosis/surgery
*Gastrostomy/adverse effects/methods
Male
Middle Aged
Risk Factors
Female
Retrospective Studies
*Postoperative Complications/etiology/epidemiology
Aged
Adult
Enteral Nutrition/adverse effects/methods
*Gastroscopy/adverse effects

@article {pmid41633359,
year = {2026},
author = {Xie, X and Liu, J and Liang, W and Zhang, Y and Gong, X and Yuan, S and Qi, C and Huang, M and Shi, L and Hou, M and Zhang, M and Liu, W and Sun, W and Wu, Y and Li, C and Cao, Z and Jing, H and Qian, L and Liu, J and Yuan, S and Wang, Q and Shen, Y and Liu, Z and Li, Y and Pan, H and Zhu, B and Shan, B and He, K and Wang, W and Zou, C and Li, Y and Chou, JJ and Yuan, J},
title = {Repression of RIPK1 kinase by INPP5D inhibits expression of diverse proinflammatory mediators and late-onset Alzheimer's disease risk factors.},
journal = {Immunity},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.immuni.2026.01.014},
pmid = {41633359},
issn = {1097-4180},
abstract = {Genome-wide association studies strongly implicate neuroinflammation in late-onset Alzheimer's disease (LOAD). Genetic risk loci for LOAD are enriched for genes expressed in microglia, but the relationship among microglial LOAD risk genes has been unclear. We found that the N-terminal SH2 domain of INPP5D, an important LOAD risk gene, directly interacted with the cell death regulator RIPK1 at p-Y383 to suppress RIPK1 kinase activation. Microglial INPP5D deficiency cell-autonomously promoted RIPK1-mediated transcriptional induction of diverse LOAD risk genes, proinflammatory cytokines, complements, and ROS mediators, as well as proinflammatory signaling mediators such as Toll-like receptors (TLRs), MyD88, Nlrp3, gasdermin D, and Zbp1. RIPK1-regulated microglial transcriptomic signatures were found in microglial subtypes implicated in human Alzheimer's disease (AD) pathogenesis. Furthermore, microglial INPP5D deficiency promoted aging-dependent RIPK1-mediated development of neuronal TDP-43 pathology, neuronal loss, and motor dysfunction in a non-cell-autonomous manner. Our data suggest that INPP5D functions as an intracellular rheostat in regulating RIPK1-mediated neuroinflammation for promoting aging-related neurodegenerative diseases, including LOAD and AD-amyotrophic lateral sclerosis comorbidity.},
}

@article {pmid41633321,
year = {2026},
author = {Di Gennaro, G and Grammaldo, LG and Tomasini, A},
title = {Toward a multidimensional understanding of internalized epilepsy stigma.},
journal = {Epilepsy & behavior : E&B},
volume = {177},
number = {},
pages = {110899},
doi = {10.1016/j.yebeh.2026.110899},
pmid = {41633321},
issn = {1525-5069},
abstract = {This letter responds to Prieto et al.'s discussion of our article Rethinking epilepsy stigma: the uncanny, the emotional, and the structural. We clarify that our original framework was primarily theoretical, aiming to illuminate the multifaceted mechanisms sustaining internalized epilepsy stigma, including the "uncanny" experience of seizures, ambivalent emotional responses, and structural inequities. We highlight how third-generation psychotherapeutic approaches, emphasizing psychological flexibility, mindfulness, and emotional acceptance, complement cognitive-behavioral strategies by enhancing individuals' capacity to relate adaptively to stigma-related distress. We propose that integrating behavioural, emotional, and structural perspectives offers a multidimensional framework to better understand and address internalized epilepsy stigma, guiding interventions that promote psychological well-being, social inclusion, and empowerment for people living with epilepsy.},
}

@article {pmid41631638,
year = {2026},
author = {Allen, S and Howard, J and McDermott, CJ and Boardman, F and McNeill, A},
title = {Limited data capture on reproductive medicine use in amyotrophic lateral sclerosis: implications for monitoring access.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-3},
doi = {10.1080/21678421.2026.2618124},
pmid = {41631638},
issn = {2167-9223},
abstract = {There is very limited evidence around the use of reproductive genetic testing in individuals with amyotrophic lateral sclerosis (ALS)-linked gene variants. This study aimed to identify the use of reproductive genetic testing in these individuals to understand patterns of (under)utilization and to identify barriers to equitable access. Freedom of information requests were sent in January 2025 to the 22 regional clinical genetics centers across the UK around reproductive services for individuals with, or at risk for, ALS and Huntington's disease. Limited data were available with only six trusts answering in full. The data that our study yielded raises significant concerns and inconsistencies regarding clinical recording and reporting of reproductive genetic counseling and testing. The absence of standardized retrievable data limits the ability to assess utilization and may point toward a systemic issue in data capture of reproductive genetic services for individuals at risk of ALS, and by extension, those affected by other genetic conditions.},
}