@article {pmid42504602,
year = {2026},
author = {Eisen, A and Durham, HD and Pioro, E},
title = {The aging brain that doesn't fail: how neural resilience masks neurodegeneration.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-15},
doi = {10.1080/21678421.2026.2705693},
pmid = {42504602},
issn = {2167-9223},
abstract = {Neurodegenerative diseases such as amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease are usually framed as consequences of aging-related pathogenic processes, including impaired proteostasis with protein aggregation, mitochondrial dysfunction, oxidative stress, and neuroinflammation. Yet, most individuals, even into advanced age, do not develop clinically significant neurodegenerative disease. This discrepancy suggests that the nervous system possesses robust and redundant protective mechanisms that maintain neural integrity despite cumulative molecular and cellular stress. In this perspective, we propose that neurodegenerative diseases arise not simply from the presence of pathogenic processes, but when integrated resilience systems fail to maintain homeostasis or when reserve mechanisms no longer compensate for accumulated pathology. We have synthesized a threshold-based model of disease emergence based on evidence across proteostasis, mitochondrial function, neuroimmune regulation, glial biology, network-level compensation, and barrier integrity, while integrating genetic, environmental, developmental, and stochastic modifiers. We distinguish biological resilience, which actively limits or repairs pathology, from reserve, which permits function despite pathology. We further propose that clinical disease emerges only when age-related cumulative stress exceeds the combined capacity of resilience and reserve. Reframing neurodegeneration as a failure of preservation systems offers new directions for prevention and therapeutic development.},
}

@article {pmid42505224,
year = {2026},
author = {Collaço, N and Kennington, A and Greenberg, N and Imber, T and Warne, D and Sodergren, S},
title = {Mapping Support-Seeking After Cancer Treatment: A Co-Designed Model of Triggers, Timing and Support Pathways in Young People with Lived Experience of Cancer.},
journal = {Current oncology (Toronto, Ont.)},
volume = {33},
number = {7},
pages = {},
pmid = {42505224},
issn = {1718-7729},
mesh = {Humans ; *Neoplasms/psychology/therapy ; *Social Support ; Female ; Male ; Young Adult ; Adolescent ; *Help-Seeking Behavior ; Adult ; },
abstract = {Post cancer treatment, many young people often live with ongoing emotional, social, and physical difficulties, but support is not always accessed when it is needed. This study aimed to co-produce a conceptual model of support-seeking after cancer treatment with young people with lived experience of cancer, to better understand the triggers, timing, and pathways influencing engagement with support. This co-design work, informed by Bird et al.'s generative framework for co-production, built upon a prior study involving interviews and co-design workshops with young people and healthcare/allied health professionals, and informed a preliminary model of support-seeking. The current work involved two further co-production stages through an online survey and workshop to refine this model. Data were analysed using a thematic approach to support conceptual model development. Four interconnected themes shaped support-seeking: (1) readiness to engage: recognition, emotional readiness, and relational safety; (2) access and appraisal of support: visibility, fit, feasibility, and burden; (3) pathways to support: multi-modal, layered, and non-linear engagement; and (4) support trajectory: changing needs and recurrent engagement. Engagement in support-seeking depended on the alignment of readiness, recognition of need, and relational safety. This model offers a framework to improve how post-treatment support is designed and delivered in practice.},
}

Humans
*Neoplasms/psychology/therapy
*Social Support
Female
Male
Young Adult
Adolescent
*Help-Seeking Behavior
Adult

@article {pmid42505342,
year = {2026},
author = {Yang, CS and Ma, Y and Xie, JL and Lou, XY and Lv, YT and Wu, TX and Xu, HF and Zou, SM and Wu, ZY and Li, HF},
title = {Pathogenicity Classification of TARDBP Variants of Uncertain Significance: An Integrative Clinical Characterization and Functional Validation.},
journal = {Cells},
volume = {15},
number = {14},
pages = {},
pmid = {42505342},
issn = {2073-4409},
support = {2025ZD1802600//Innovative Drug Research and Development National Science and Technology Major Project/ ; },
mesh = {Humans ; *DNA-Binding Proteins/genetics/chemistry/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/pathology ; Mutation/genetics ; Female ; Genetic Variation ; },
abstract = {TAR DNA binding protein (TARDBP) is one of the major causative genes of amyotrophic lateral sclerosis (ALS), which drives disease progression through both gain-of-toxicity (GOT) and loss-of-function (LOF) mechanisms. The mutant TDP-43 exhibits aberrant nucleocytoplasmic distribution and forms cytotoxic hyperphosphorylated aggregates, a process that can be robustly recapitulated in vitro. Thus, functional assays in cell lines serve as a reliable metric for the pathogenicity classification of TARDBP variants. In this study, we performed in vitro experiments to classify the pathogenicity of 28 TARDBP variants of uncertain significance (VUS) among the 172 previously reported TARDBP variants. 22 of these VUS were determined to be functionally abnormal, of which 12 could be further classified as likely pathogenic (LP) variants according to American College of Medical Genetics (ACMG) and the ClinGen Sequence Variant Interpretation (SVI) Working Group guidelines. We also summarized the clinical characteristics of 35 ALS patients carrying 12 variants in the TARDBP gene. Pathogenic missense variants were predominantly clustered in the C-terminal domain (CTD) of TARDBP. Variants in TARDBP exon 6 may lead to an earlier age at onset. ALS caused by TARDBP mutations exhibits marked phenotypic heterogeneity, along with incomplete penetrance in carriers. Patient-derived primary skin fibroblasts serve as a feasible cellular model for the functional assessment of variant pathogenicity. Our findings expand the TARDBP mutation spectrum, and provides a preliminary basis for preclinical research on TARDBP-targeted therapies for ALS.},
}

Humans
*DNA-Binding Proteins/genetics/chemistry/metabolism
*Amyotrophic Lateral Sclerosis/genetics/pathology
Mutation/genetics
Female
Genetic Variation

@article {pmid42505348,
year = {2026},
author = {Liu, B and Zhang, L and Lv, B and Xu, C and Han, L and Yan, Q and Wang, X},
title = {Copper Homeostasis and Cuproptosis in Neurodegenerative Diseases.},
journal = {Cells},
volume = {15},
number = {14},
pages = {},
pmid = {42505348},
issn = {2073-4409},
mesh = {Humans ; *Copper/metabolism ; *Cuproptosis ; *Homeostasis ; *Neurodegenerative Diseases/metabolism/pathology ; Animals ; Mitochondria/metabolism ; Proteotoxic Stress ; },
abstract = {Copper is an essential trace element required for numerous enzymatic processes in the brain, including mitochondrial metabolism, antioxidant defense, and gene expression regulation. Recent studies have further implicated copper in a newly defined form of regulated cell death termed cuproptosis, providing a mechanistic framework for copper-dependent cytotoxicity. Increasing evidence indicates that copper dyshomeostasis is a common feature of major neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), where it is associated with protein misfolding, redox imbalance, and neuronal vulnerability. Nevertheless, the mechanistic link between copper dysregulation and neuronal cell death remains incompletely defined. In this review, we systematically summarize the molecular mechanisms governing copper homeostasis and intracellular copper trafficking, while providing a timely, updated, and in-depth overview of the mechanistic basis and emerging biology of cuproptosis. We further comprehensively evaluate the current evidence linking copper dysregulation and cuproptosis-related pathways to neurodegenerative diseases, with particular emphasis on distinguishing mechanistic causation from pathological correlation. Importantly, we discuss current therapeutic strategies and emerging clinical efforts targeting copper metabolism, while highlighting the major challenges in defining the pathological significance and mechanistic contribution of cuproptosis in neurodegenerative diseases. Collectively, this review provides an updated framework for understanding the pathological significance and translational potential of cuproptosis in neurodegenerative diseases.},
}

Humans
*Copper/metabolism
*Cuproptosis
*Homeostasis
*Neurodegenerative Diseases/metabolism/pathology
Animals
Mitochondria/metabolism
Proteotoxic Stress

@article {pmid42506061,
year = {2026},
author = {Zeng, CW},
title = {Protein-First, but Not Protein-Only: Rethinking Neurodegenerative Diseases Through Transgenic Mouse Models.},
journal = {Neurology international},
volume = {18},
number = {7},
pages = {},
doi = {10.3390/neurolint18070139},
pmid = {42506061},
issn = {2035-8385},
abstract = {Neurodegenerative diseases represent a major and growing global health burden. Although these disorders are often clinically defined by symptoms and affected brain regions, many are mechanistically linked to abnormal protein accumulation, misfolding, impaired proteostasis, RNA dysregulation, mitochondrial dysfunction, and neuroinflammation. In this Perspective article, I discuss major neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, amyotrophic lateral sclerosis, frontotemporal dementia, Huntington's disease, prion diseases, spinocerebellar ataxias, and spinal muscular atrophy, through the lens of disease-associated proteins and experimental modeling. I argue that a protein-centered framework provides a useful approach for understanding disease mechanisms and selecting transgenic mouse models, while recognizing that aging, cellular context, neuroinflammation, mitochondrial dysfunction, vascular dysfunction, and other disease modifiers also shape neurodegeneration. Transgenic and genetically engineered mouse models have been essential for dissecting the pathogenic roles of amyloid-β, tau, α-synuclein, TDP-43, SOD1, FUS, C9ORF72-associated dipeptide repeat proteins, mutant huntingtin, prion protein, ataxins, and SMN deficiency. However, these models have important limitations, including artificial overexpression, familial mutation bias, species differences, and incomplete representation of aging-related sporadic diseases. Rather than seeking a single "best" model, a more productive strategy is to adopt model portfolios tailored to specific biological questions and to integrate mouse studies with human cellular models, postmortem tissue, omics approaches, and biomarker-based validation. Such an approach may improve mechanistic insight, strengthen translational relevance, and enhance the predictive value of preclinical neurodegenerative disease research.},
}

@article {pmid42506583,
year = {2026},
author = {Remus, S and Donelle, L and Bauer, M and Nagle, L},
title = {A Nursing Homecare Data Science Investigation Using "Persons with ALS" (PALS) Electronic Health Records (EHRs).},
journal = {The Canadian journal of nursing research = Revue canadienne de recherche en sciences infirmieres},
volume = {},
number = {},
pages = {8445621261469904},
doi = {10.1177/08445621261469904},
pmid = {42506583},
issn = {1705-7051},
abstract = {BackgroundData science, rooted in computer science, statistics, and information science is advancing healthcare research by unlocking "insights" from big data to discover knowledge about patient experiences and answer previously unanswerable questions. The comparatively limited engagement of Canadian nurse researchers in this field, relative to counterparts in other jurisdictions (e.g., United States) served as a key impetus for initiating this data science study.PurposeTo investigate homecare electronic health records (EHRs) of "persons with ALS" (PALS) disease and identify care-related factors that influence their preferences and ability to be safely supported at home.MethodGuided by a nursing informatics' data, information, knowledge, wisdom (DIKW) framework and the knowledge discovery in databases (KDD) methodology, a retrospective, secondary analysis of an integrated dataset (1159 clinical assessments and administrative data) documenting 240 PALS's homecare encounters (April 1, 2009 - July 31, 2019) was conducted. EHR data was analyzed using correlations and logistic regression to model institutionalization risk factors of PALS.ResultsFive significant models were generated that accurately distinguished PALS institutionalization status (at home/not home) while offering comparable predictive performance. The final model featuring six factors offers homecare providers real-time insights into PALS clinical status at the point of care. Four relate to ALS clinical manifestations of disease decline and two assessment outcome measures (MAPLe and CHESS), strongly predicting institutionalization and caregiver burden.ConclusionBig data science offers nurse researchers a transformative way to advance knowledge development that supports high-quality, sustainable healthcare delivery while fulfilling an intended benefit of EHRs.},
}

@article {pmid42507931,
year = {2026},
author = {Ozguney, B and Puterbaugh, RZ and Viswanathan, R and Shenoy, J and Mohanty, P and Mittal, J and Fawzi, NL},
title = {Methionine oxidation alters both helical assembly and disordered contacts in human TDP-43 C-terminal domain phase separation.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {123},
number = {31},
pages = {e2537431123},
doi = {10.1073/pnas.2537431123},
pmid = {42507931},
issn = {1091-6490},
support = {R01NS116176//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; not applicable//Radala Foundation/ ; },
abstract = {TAR DNA binding protein 43 (TDP-43), a key protein linked to ALS pathology, undergoes phase separation and forms functional assemblies via condensation within cells. The conserved region (CR) within its C-terminal domain (CTD) mediates self-assembly through helix-helix interactions, while the flanking intrinsically disordered regions (IDRs) contribute to phase separation through transient interactions involving aromatic and hydrophobic residues. The CTD contains ten methionine residues distributed equally between these regions, making it particularly susceptible to oxidative modifications. While methionine oxidation is known to impair TDP-43 phase separation, neither the precise mechanism nor the specific contribution of methionines in the CR compared to the IDRs has been determined. Here, we combine NMR spectroscopy and molecular dynamics (MD) simulations to reveal if and how methionine oxidation in each region differentially affects CTD structure and phase separation. To assess the change of secondary structure caused by oxidation, we measured NMR random coil chemical shift values for methionine sulfoxide. Oxidation of CR methionines disrupts helical structure and directly impairs intermolecular helical association, while oxidation of IDR methionines disrupts long-range contacts. Hence, oxidation of methionines in both regions contributes to impaired phase separation, albeit through different mechanisms. These findings establish methionines as critical redox-sensitive modulators in TDP-43 phase behavior and provide molecular insights into how oxidative stress may contribute to TDP-43 dysregulation in neurodegenerative diseases.},
}

@article {pmid42508294,
year = {2026},
author = {Liu, X and Fu, W and Cui, X and Feng, Y and Wen, B and Shan, L and Xu, X and Yang, J and Zhang, J and He, L and Zang, Y and Zhao, S and Yao, X and Liu, Y and Ma, M and Du, B and Dang, J and Zou, Z and Feng, H and Lu, Z and Zhang, Y and Wu, Z and Shang, H and Yin, P and Fan, D},
title = {Huoling Shengji granule in amyotrophic lateral sclerosis: A multicenter, randomized, double-blind, riluzole-controlled trial.},
journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics},
volume = {23},
number = {5},
pages = {e00953},
doi = {10.1016/j.neurot.2026.e00953},
pmid = {42508294},
issn = {1878-7479},
abstract = {Currently, no curative therapies exist for Amyotrophic Lateral Sclerosis (ALS). This study aimed to evaluate the efficacy and safety of Huoling Shengji granules (HLSJ), a traditional Chinese medicine (TCM), compared to the standard treatment riluzole. A multicenter, randomized, double-blind, double-dummy, active-controlled Phase II clinical trial was conducted across 11 centers in China. A total of 140 ALS patients were randomly assigned (1:1) to receive either HLSJ or riluzole for 48 weeks. The primary endpoint, analyzed in the full analysis set (FAS), was the change in the ALS Functional Rating Scale-Revised (ALSFRS-R) score from baseline to Week 48. Safety profiles were comparable between groups, with no significant difference in adverse events (80.28% vs. 80.56%, P = 0.9671). Analysis using the pre-specified Last Observation Carried Forward (LOCF) method showed a numerical advantage for HLSJ (1.07 points) but lacked statistical superiority. However, a more scientific analysis using the Mixed Model for Repeated Measures (MMRM), recommended for progressive diseases, indicated that HLSJ was significantly superior to riluzole in slowing ALSFRS-R score decline (Least Squares Mean Difference [LSMD]: 2.29 points; 95% confidence interval [CI]: 0.52 to 4.06; P = 0.0114). While the LOCF model showed no statistical difference, the MMRM analysis confirmed that HLSJ demonstrated significant efficacy superior to riluzole with a favorable safety profile. These findings provide a critical basis for conducting pivotal Phase III confirmatory trials of HLSJ for ALS treatment.},
}

@article {pmid42508356,
year = {2026},
author = {Wu, W and Lalli, GS and Wu, H},
title = {Linking Big Five personality traits to L2 willingness to communicate with GenAI chatbots: A mixed-methods study of the mediating role of regulatory focus.},
journal = {Acta psychologica},
volume = {269},
number = {},
pages = {107516},
doi = {10.1016/j.actpsy.2026.107516},
pmid = {42508356},
issn = {1873-6297},
abstract = {Generative artificial intelligence (GenAI) chatbots are increasingly used for second language (L2) speaking practice, yet learners' willingness to communicate (WTC) with them remains insufficiently understood. Building on MacIntyre et al.'s (1998) Pyramid Model, this study examined how the Big Five personality traits and regulatory focus jointly shape L2 WTC in GenAI-mediated interaction. Survey data from 426 Chinese university learners were analyzed using Partial Least Squares Structural Equation Modeling, complemented by qualitative thematic analysis. Openness emerged as the only trait directly predicting WTC and was positively associated with both promotion and prevention focus. Agreeableness positively predicted prevention focus, whereas Extraversion showed a negative association; Conscientiousness and Neuroticism were unrelated to regulatory focus. Prevention focus, but not promotion focus, significantly predicted WTC. Indirect effects indicated that Openness and Agreeableness enhanced WTC through prevention focus, while Extraversion exerted a negative indirect effect. Qualitative analysis identified four themes, with psychological safety and controllability explaining why prevention-focused learners favored GenAI. Together, the findings suggest that GenAI's de-socialized, low-risk interaction environment reshapes how personality and motivational dispositions translate into L2 WTC, offering implications for both L2 pedagogy and the design of GenAI-supported speaking tools.},
}

@article {pmid42508391,
year = {2026},
author = {Gao, W and Lee, HY and Min, KJ},
title = {Aging-Related Metaflammation and Mitochondrial Dysfunction in Neurodegenerative Diseases.},
journal = {Aging and disease},
volume = {},
number = {},
pages = {},
doi = {10.14336/AD.2026.0366},
pmid = {42508391},
issn = {2152-5250},
abstract = {Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) are increasingly recognized as manifestations of aging-associated systemic dysfunction, rather than isolated brain disorders. Central to this dysfunction is the interplay among metaflammation, mitochondrial breakdown, and chronic neuroinflammation. Metaflammation, driven by peripheral metabolic stress, may prime the brain's immune environment through cytokine signaling and blood-brain barrier compromise. This metabolic-inflammatory crosstalk is thought to impair mitochondrial integrity in neurons and glial cells, promoting oxidative stress and the release of pro-inflammatory mitochondrial components. These mitochondrial signals, in turn, may activate microglial and astrocytic innate immune responses, creating a potentially self-reinforcing cycle of neuroinflammation and energy failure that may contribute to neuronal loss. This review outlines a proposed framework linking metaflammation to neurodegeneration, emphasizing shared mechanisms across AD, PD, and ALS. We further examine preclinical and clinical advances in therapeutic strategies that target this axis including anti-inflammatory agents, caloric restriction, mitophagy enhancers, mitochondrial antioxidants, and senescence-targeted therapies. Together, these interventions reflect a shift from symptom management to systemic metabolic and immune modulation, offering a unified framework for understanding and potentially influencing age-related neurodegeneration.},
}

@article {pmid42508540,
year = {2026},
author = {Sun, R and Duan, X and Wang, X and Liu, J and Li, Z and Wang, Y},
title = {R-loops: Biological Functions, Regulatory Mechanisms, and Therapeutic Implications in Brain Diseases-A Review.},
journal = {Molecular and cellular probes},
volume = {},
number = {},
pages = {102081},
doi = {10.1016/j.mcp.2026.102081},
pmid = {42508540},
issn = {1096-1194},
abstract = {BACKGROUND: R-loops are three-stranded nucleic acid structures formed by a DNA-RNA hybrid and a displaced single-stranded DNA. They regulate transcription, replication, and DNA repair, but their dysregulation causes genomic instability and inflammation, contributing to brain diseases. The nervous system exhibits selective vulnerability to R-loop stress due to ultra-long gene transcription, post-mitotic longevity, and high metabolic demands.

METHODS: This review synthesizes current literature from PubMed, Scopus, Web of Science, and Embase (2010-2026) on R-loop biology, with a focus on brain-specific mechanisms, regulatory factors (SETX, ZPR1, METTL3, TDP-43/FUS), and disease models.

RESULTS: In neurodegeneration, R-loop accumulation drives repeat expansion disorders (Fragile X, Huntington's disease) and loss-of-function SETX mutations (AOA2), whereas gain-of-function SETX (L389S) causes pathological R-loop depletion in ALS4, disrupting TGF-β signaling. TDP-43/FUS and SMN are integral to R-loop resolution, unifying ALS/FTD and SMA. In brain cancers, METTL3-mediated m[6]A modification of TERRA stabilizes telomeric R-loops in ALT-positive neuroblastoma, creating a therapeutic vulnerability to METTL3 inhibitors (STM2457, STC-15). Glioma stem cells rely on m[6]A-modified circPOLR2B to regulate R-loop formation and malignancy. Clinical-stage agents (EP102, TUG1ASO, ATX-559) and R-loop-derived prognostic signatures (RLPI) are emerging, but translation is hindered by a lack of non-invasive biomarkers and the dual physiological/pathological roles of R-loops.

CONCLUSIONS: R-loops are central to brain disease pathogenesis, offering promising therapeutic targets. Future research should prioritize precision R-loop modulators, non-invasive biomarkers, and combinatorial strategies.},
}

@article {pmid42508631,
year = {2026},
author = {Alanazi, SM and Al-Kuraishy, HM and Alexiou, A and Papadakis, M and Faheem, SA and Batiha, GE},
title = {Isoform-selective HSP90 inhibition as a precision therapeutic strategy for neurodegenerative and metabolic diseases.},
journal = {Progress in neuro-psychopharmacology & biological psychiatry},
volume = {149},
number = {},
pages = {111834},
doi = {10.1016/j.pnpbp.2026.111834},
pmid = {42508631},
issn = {1878-4216},
abstract = {Heat shock protein 90 (HSP90) is a central regulator of cellular proteostasis, coordinating the folding, stabilization, and turnover of a wide range of client proteins in the cytosol, endoplasmic reticulum, and mitochondria. Accumulating evidence indicates that the four HSP90 paralogs HSP90α, HSP90β, GRP94, and TRAP1 have distinct pathological roles in neurodegenerative and metabolic diseases. In neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, aberrant HSP90 activity contributes to the persistence of toxic protein conformers, defective autophagy, mitochondrial dysfunction, and chronic neuroinflammation. In metabolic disorders such as obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease, GRP94- and TRAP1-dependent signaling promotes endoplasmic reticulum stress, impaired mitochondrial metabolism, insulin resistance, and inflammatory remodeling. These mechanistic insights have accelerated the development of a new generation of HSP90 inhibitors with improved selectivity, tissue targeting, and brain penetration. Unlike earlier pan-HSP90 inhibitors, these compounds are designed to exploit paralog-specific vulnerabilities and may enable safer long-term modulation of disease-relevant chaperone networks. This review summarizes current advances in the biology and pharmacology of HSP90 paralogs and proposes isoform-selective HSP90 targeting as a promising therapeutic strategy at the intersection of neurodegeneration and metabolic dysfunction.},
}

@article {pmid42508735,
year = {2026},
author = {Piccolo, LL and Panto, C and Yeewa, R and Yubolphan, R and Poound, P and Potikanond, S and Jantrapirom, S},
title = {Context-dependent YEATS-domain inhibition enhances neuronal resilience and improves ALS phenotypes.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107549},
doi = {10.1016/j.nbd.2026.107549},
pmid = {42508735},
issn = {1095-953X},
abstract = {Neuronal loss in neurodegenerative disease is driven in part by maladaptive stress signaling and impaired adaptation to proteotoxic challenges. ENL and AF9 are YEATS-domain acyl-lysine reader proteins best characterized in leukemia, but their functions in neurons remains unclear. Here, we defined the role of the ENL/AF9 YEATS domain using complementary chemical and genetic perturbations. We applied the selective YEATS inhibitor SR-0813 in differentiated human neurons and modulated ENL/AF9 activity in Drosophila using either SR-0813 or ENL/AF9 knockdown. In flies, SR-0813 phenocopied ENL/AF9 knockdown by extending lifespan and enhancing stress tolerance. To test disease-context specificity, we performed a Drosophila genetic modifier screen across neurodegeneration models. ENL/AF9 reduction was beneficial in UBQLN2[P497H] and SOD1[G94A] but showed reduced efficacy or became detrimental in chronic aggregation or mitochondrial stress models such as (GGGGCC)49 and polyQ disease. In human neurons, SR-0813 improved survival across multiple stress conditions, with the strongest protection during endoplasmic reticulum stress. Mechanistically, ENL/AF9 YEATS inhibition dampened PERK-dependent integrated stress response signaling and reduced apoptotic commitment without broadly enhancing proteostasis capacity. Together, these findings identified ENL/AF9 as modulators of neuronal stress-response dynamics and established ENL/AF9 YEATS-domain inhibition as a context-dependent strategy to enhance neuronal resilience with relevance to ALS and related proteotoxic disorders.},
}

@article {pmid42509371,
year = {2026},
author = {Ran, X and Wuu, J and Qin, ZS and McDermott, MP and Cooper-Knock, J and Li, Y and Granit, V and Grignon, AL and Lin, E and Fernandez, MC and Colato, D and Carberry, N and Lill, CM and Piazza, P and Malaspina, A and Benatar, M},
title = {Longitudinal plasma proteomics predict phenoconversion to clinically manifest ALS.},
journal = {Nature medicine},
volume = {},
number = {},
pages = {},
pmid = {42509371},
issn = {1546-170X},
support = {R01 NS105479, U54 NS092091//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01 NS105479, U54 NS092091//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01 NS105479/NS/NINDS NIH HHS/United States ; R01 NS105479/NS/NINDS NIH HHS/United States ; R01 NS105479, U54 NS092091//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; 4365, 172123//Muscular Dystrophy Association (Muscular Dystrophy Association Inc.)/ ; 4365, 172123//Muscular Dystrophy Association (Muscular Dystrophy Association Inc.)/ ; 4365, 172123//Muscular Dystrophy Association (Muscular Dystrophy Association Inc.)/ ; 2015, 16-TACL-242//Amyotrophic Lateral Sclerosis Association (ALS Association)/ ; 2015, 16-TACL-242//Amyotrophic Lateral Sclerosis Association (ALS Association)/ ; 2015, 16-TACL-242//Amyotrophic Lateral Sclerosis Association (ALS Association)/ ; },
abstract = {The study of pre-symptomatic amyotrophic lateral sclerosis (ALS) and the design of disease prevention trials are greatly hampered by our inability to predict which unaffected carriers of ALS-associated pathogenic variants will phenoconvert to clinically manifest disease and when. In this longitudinal Olink Explore, high-throughput, proteomic study, 516 serially collected plasma samples from 33 phenoconverters, 35 patients with ALS, 10 pre-symptomatic pathogenic variant carriers and 59 controls were included. Here we identified 92 proteins with concentrations that changed before phenoconversion; characterized the longitudinal trajectory of these proteins and identified a core panel of 19 proteins which, collectively, predicted phenoconversion over the 0.5-year to 5-year time horizons (crossvalidated areas under the curve 0.80-0.89) and yielded estimates of time to phenoconversion with a mean absolute error of 1.6 years. These findings were partially replicated in UK Biobank data, confirming pre-symptomatic increases in several proteins (for example, NEFL, EDA2R and CA3) and that a multi-protein panel outperformed NEFL alone in estimating time to phenoconversion. This work sheds light on the biology of pre-symptomatic ALS. Moreover, our identification of a panel of new susceptibility/risk biomarkers based on empirical longitudinal data furthers the ultimate goal of ALS prevention.},
}

@article {pmid42509459,
year = {2026},
author = {Sellin, J and Öijerstedt, L and von der Gablentz, J and Chamoun, S and Kläppe, U and Press, R and Samuelsson, K and Grosskreutz, J and Ingre, C},
title = {Plasma cardiac troponin T complements neurofilament light chain by reflecting disease phase and phenotypic variation in amyotrophic lateral sclerosis.},
journal = {Journal of neurology},
volume = {273},
number = {8},
pages = {},
pmid = {42509459},
issn = {1432-1459},
support = {GR 1578/6-1//Deutsche Forschungsgemeinschaft/ ; GR 1578/9-1//Deutsche Forschungsgemeinschaft/ ; EXC 2167/2 - 390884018//Germany`s Excellence Strategy/ ; },
abstract = {BACKGROUND: Neurofilament light chain (NfL) is an established marker of neuronal injury and disease aggressiveness in amyotrophic lateral sclerosis (ALS). In contrast, the clinical and biological significance of cardiac troponin T (cTnT) in ALS is not fully understood. We aimed to evaluate the relationship between plasma cTnT and disease aggressiveness, progression stage, and clinical phenotype in comparison with NfL.

METHODS: Plasma cTnT and cerebrospinal fluid (CSF) NfL were analysed at diagnosis in a population-based cohort of 526 patients with ALS. Disease aggressiveness was modelled using the D50 framework, which quantifies the time taken to lose 50% of functional capacity (ALSFRS-R) and normalises individual disease trajectories. Biomarker associations with disease aggressiveness, phase, and clinical variables were assessed through group comparisons, logistic and linear regression, and receiver operating characteristic analyses.

RESULTS: Neurofilament light chain in CSF was strongly associated with disease aggressiveness, with higher levels in patients with more aggressive disease. In contrast, plasma hs-cTnT did not correlate with D50. Across disease phases, CSF NfL remained relatively stable, whereas plasma hs-cTnT increased with advancing rD50, suggesting accumulation with disease progression. Plasma hs-cTnT levels were higher in patients with spinal compared to bulbar onset. Combined biomarker models improved sensitivity and negative predictive value for identifying less aggressive disease.

CONCLUSION: Plasma hs-cTnT and CSF NfL capture distinct but complementary dimensions of ALS pathology. While NfL reflects disease aggressiveness, hs-cTnT aligns with disease phase and clinical phenotype, supporting its use as a complementary biomarker for ALS characterisation and monitoring.},
}

@article {pmid42510076,
year = {2026},
author = {Uzun, E and İçöz, D and Apaydın, BK and Orhan, K},
title = {Investigation of the Use of Artificial Intelligence in Anterior Loop Detection: A Panoramic Radiography Study.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {16},
number = {14},
pages = {},
pmid = {42510076},
issn = {2075-4418},
support = {2024HZDP003//Pamukkale University/ ; },
abstract = {Background/Objectives: The accurate detection of the anterior loop (AL) of the inferior alveolar nerve is critical to avoid neurosensory complications during surgical procedures in the interforaminal region, and panoramic radiography continues to be widely used in routine dental diagnostics due to its accessibility and cost-effectiveness. This study aimed to evaluate the performance of a deep learning approach in automatic detection of the AL in panoramic radiographs. Methods: A total of 305 anonymised panoramic radiographs containing 413 annotated ALs were used to train a YOLOv8x-based model for automatic AL detection. The dataset was divided into training, validation, and test sets consisting of 245 images (332 AL annotations), 30 images (40 AL annotations), and 30 images (41 AL annotations). Labelling was carried out by using the polygonal annotation method. The model's performance in identifying the AL region was measured using precision, recall, F1 score, and mean average precision (mAP@0.5). Results: The model achieved a precision of 0.75, a recall of 0.6585, and a F1 score of 0.7013. The average precision at an intersection over union (IoU) threshold of 0.5 (mAP@0.5) was 0.739. Conclusions: This study demonstrates the feasibility of using a YOLOv8x-based detection model to detect ALs in panoramic radiographs. Although further improvements are needed to enhance model sensitivity and generalisability, the findings demonstrate the potential to support clinical decision-making.},
}

@article {pmid42510722,
year = {2026},
author = {Avitabile, A and Rusciano, D and Amato, R and Cannizzaro, L and Gagliano, C},
title = {Sex-Dependent Brain Plasticity in Neurological Disease: From Biological Variability to Adaptive, Compensatory, and Maladaptive Trajectories.},
journal = {Biology},
volume = {15},
number = {14},
pages = {},
doi = {10.3390/biology15141176},
pmid = {42510722},
issn = {2079-7737},
abstract = {Brain plasticity is often described as the capacity of the nervous system to change in response to development, experience, injury, disease, or treatment. That definition is useful, but it can obscure two clinically important points: plasticity is biologically constrained, and change is not always beneficial. This narrative review examines sex-dependent brain plasticity as a context-sensitive process rather than as a simple male-female contrast. We distinguish four operational outcomes of plasticity: (i) reparative plasticity, which restores structure or function; (ii) compensatory plasticity, which preserves performance through alternative or more costly strategies; (iii) insufficient plasticity, in which reorganization is too weak or unstable to sustain function; and (iv) maladaptive plasticity, in which plastic change reinforces dysfunction, pain, excitability, rigidity, or decline. We also define adaptive reserve as the integrated capacity of neural, glial, vascular, immune, metabolic, endocrine, and gene-regulatory systems to support useful reorganization under stress. The review evaluates endocrine, synaptic, neuroimmune, mitochondrial, vascular, stress-related, and epigenetic mechanisms, indicating where evidence for sex-dependent effects is relatively strong and where it remains indirect, inconsistent, or context-dependent. Disease examples include autism spectrum disorder, attention-deficit/hyperactivity disorder, epilepsy, intellectual disability, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, traumatic and ischemic injury, multiple sclerosis, chronic pain, aging, and systemic metabolic or inflammatory disorders. Throughout, biological sex is separated from gender-related social, diagnostic, and health-care determinants. We conclude that therapeutic strategies should not aim simply to enhance plasticity, but to guide it by matching intervention, timing, dose, biological readiness, and monitoring to the patient's adaptive state.},
}

@article {pmid42511587,
year = {2026},
author = {Korošec, T and Rogelj, B and Župunski, V},
title = {LINE-1 Retrotransposons and Amyotrophic Lateral Sclerosis.},
journal = {International journal of molecular sciences},
volume = {27},
number = {14},
pages = {},
pmid = {42511587},
issn = {1422-0067},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive degeneration of upper and lower motor neurons. While monogenic causes account for a minority of cases, in most cases, ALS is sporadic and likely arises from multilayer interactions of genetic architecture, aging-associated loss of genome regulation, and inflammatory stress. Long interspersed nuclear element-1 (LINE-1) retrotransposons are endogenous mobile elements that are tightly controlled through various cellular mechanisms under normal conditions. When abnormally active, they are involved in gene inactivation, expression regulation, and genomic instability, leading to cellular processes such as innate immunity and cell death. Here, we present mechanistic links between LINE-1 and ALS. These include evidence that the burden of retrotransposition-competent LINE-1s (RC-L1s) is increased in ALS genomes, positioning RC-L1 load as a candidate contributor to missing heritability in sporadic disease. We also integrate emerging data showing that LINE-1 RNA can be intrinsically toxic independently of new insertions, as it promotes chromatin opening and transcriptional epigenetic noise, particularly when nuclear RNA surveillance pathways fail in TDP-43 pathology. Finally, we review how LINE-1-derived DNA/RNA intermediates can engage innate immune sensors, highlighting the cGAS-STING axis as a plausible route from LINE-1 de-repression to neuroinflammation. Together, these concepts support a model in which genetic RC-L1 load and age-/pathology-driven LINE-1 de-repression converge on nuclear dysfunction and inflammatory amplification, suggesting concrete molecular nodes for therapeutic intervention.},
}

@article {pmid42511680,
year = {2026},
author = {Podshivalova, ES and Kutsev, SI and Shestopalov, AV},
title = {The Kynurenine Pathway: Unraveling Its Role in Neurological Disorders via Mammalian Cellular Models.},
journal = {International journal of molecular sciences},
volume = {27},
number = {14},
pages = {},
pmid = {42511680},
issn = {1422-0067},
abstract = {The kynurenine pathway (KP) constitutes the primary route of tryptophan catabolism, generating a spectrum of neuroactive metabolites that profoundly influence central nervous system function. Dysregulation of the KP is increasingly recognized as a critical pathogenic mechanism underlying diverse neuropathological conditions. This review critically evaluates the most widely cited mammalian cellular models currently utilized to delineate the causal role of KP alterations in neurological disease. Specifically, this article examines primary cell cultures, immortalized and tumor-derived cell lines, stem cell-derived systems, and ex vivo organotypic brain slices and tissues, highlighting their distinct methodological advantages, translational limitations, and specific enzymatic profiles. Across the described cellular systems, a recurring mechanistic theme emerges: quinolinic acid-driven mitochondrial dysfunction, oxidative stress, and NAD+ depletion converge in neurodegenerative conditions such as Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. Conversely, kynurenic acid exhibits disorder-dependent-and at times opposing-roles, attenuating dopaminergic neurotoxicity in Parkinson's disease models while contributing to synaptic pruning deficits in schizophrenia models. Furthermore, cellular models demonstrate that IDO1/TDO induction and downstream metabolite shifts are frequently cell type- and species-dependent, complicating direct extrapolation to human pathology. Because no single experimental system achieves complete physiological fidelity, elucidating the complex dynamics of the KP and identifying novel therapeutic targets requires the integration of data across complementary platforms.},
}

@article {pmid42512084,
year = {2026},
author = {Assialioui, A and Povedano, M and Senau, M and Ferrer, I and Arias, L},
title = {Retinal Thickness and Vascular Density Changes in Amyotrophic Lateral Sclerosis Assessed by Optical Coherence Tomography Angiography.},
journal = {Biomedicines},
volume = {14},
number = {7},
pages = {},
doi = {10.3390/biomedicines14071612},
pmid = {42512084},
issn = {2227-9059},
abstract = {Background: Amyotrophic lateral sclerosis (ALS) is increasingly recognized as a multisystem disorder involving neurovascular dysfunction. The retina allows in vivo assessment of neurovascular changes. This study evaluated retinal structural and microvascular alterations in ALS using optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A). Methods: This cross-sectional study included 46 participants with ALS and 19 healthy controls. Retinal thickness and vascular density in the superficial and deep retinal capillary plexuses and the choriocapillaris were quantified using OCT and OCT-A. Group comparisons and logistic regression analyses were performed to assess associations with ALS. Subgroup analyses were conducted according to clinical phenotype. Results: In total, 124 eyes were analyzed. ALS was associated with increased average retinal thickness (p = 0.023) and reduced vascular density in the superficial retinal capillary plexus (p = 0.005), deep retinal capillary plexus (p < 0.001), and choriocapillaris (p = 0.004). In logistic regression analyses, retinal thickness was positively associated with ALS status (OR = 1.42, p = 0.023), whereas higher vascular density in the superficial plexus, deep plexus, and choriocapillaris was associated with lower odds of ALS. No significant differences were observed between bulbar- and spinal-onset ALS phenotypes. Conclusions: ALS is associated with structural and microvascular retinal alterations detectable by OCT and OCT-A. These findings support the presence of systemic neurovascular dysfunction and highlight retinal imaging as a promising, non-invasive approach for investigating disease mechanisms and developing potential biomarkers.},
}

@article {pmid42493742,
year = {2026},
author = {Criss, S and Abim-Karmon, RS and Teel, J and Rodríguez, V and Bennon, A and Wills, S and Gonzales, S and Nayreau, DD and Bharadwaj, V and Kim, HG and Woollery, J and Fair, ML},
title = {Trust, Participation, and Power: Community Perspectives from the Equity in Public Health Initiative.},
journal = {Journal of community health},
volume = {},
number = {},
pages = {},
pmid = {42493742},
issn = {1573-3610},
abstract = {Health disparities arise from unequal power relations shaping resource allocation, governance, and community agency. Community power is a key mechanism for addressing disparities. This study examines how visible, hidden, and invisible power operate within a U.S. county to inform inclusive governance. We conducted seven focus groups with Black and Hispanic residents (n = 68) and sixteen semi-structured interviews with elected officials, government staff, and advocacy leaders in Greenville County, South Carolina. Data were collected between March and December 2024. Transcripts were collaboratively coded in NVivo and analyzed using thematic analysis guided by Heller et al.'s Three Faces of Power framework. Visible power appeared through inequitable resource distribution, limited transparency, and barriers to civic participation. Hidden power functioned through faith based organizations, schools, nonprofits, and social media, connecting residents with decision makers. Invisible power reflected how socioeconomic status, race and ethnicity, immigration, and language shaped perceptions of agency and trust. Participants called for participatory structures that move beyond consultation toward shared authority and sustained engagement. Strengthening community power through structural reforms, inclusive governance practices, and targeted civic engagement may improve health outcomes and reduce disparities. Future research should examine scalable co-governance models.},
}

@article {pmid42493871,
year = {2026},
author = {Torabi, SJ and Tollefson, TT},
title = {Invited Commentary on: Fincher et al.'s "Biochemical, Mechanical, and Warping Behavior of Fresh Frozen Costal Cartilage Allograft": A Look into Rib Grafts to Be Used for Rhinoplasty from Human Donors.},
journal = {Facial plastic surgery & aesthetic medicine},
volume = {},
number = {},
pages = {26893614261472664},
doi = {10.1177/26893614261472664},
pmid = {42493871},
issn = {2689-3622},
}

@article {pmid42494173,
year = {2026},
author = {Sellin, J and Waldorf, S and von der Gablentz, J and Grehl, T and Nazlican, H and Meyer, T and Grosskreutz, J and Weydt, P and Bernsen, S},
title = {Troponin T and Neurofilament Light Chain Levels as Complementary Biomarkers of Disease Accumulation and Aggressiveness in Amyotrophic Lateral Sclerosis.},
journal = {Annals of clinical and translational neurology},
volume = {},
number = {},
pages = {},
pmid = {42494173},
issn = {2328-9503},
abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a clinically heterogeneous neurodegenerative disease requiring reliable biomarkers to improve patient stratification and trial design. While serum neurofilament light chain (sNfL) reflects neuroaxonal stress and disease aggressiveness, troponin T (TnT) may capture complementary aspects of neuromuscular involvement. We assessed the associations of TnT and sNfL with D50-derived measures of disease aggressiveness (D50) and disease accumulation (rD50) in ALS.

METHODS: In this retrospective observation, TnT and sNfL levels from ALS patients in two independent German cohorts were analyzed using the D50 disease progression model; discovery cohort (Essen, n = 433) and an independent replication cohort (Bonn, n = 185).

RESULTS: TnT levels were strongly associated with rD50-defined disease phases in the discovery cohort (p < 0.001). While not all subgroup-specific associations were replicated, the overall relationship between TnT and disease accumulation was supported in the independent replication cohort. In contrast, sNfL showed no consistent relationship with rD50-derived disease phases. sNfL concentrations demonstrated a significant inverse association with D50, supporting a relationship with disease aggressiveness across both cohorts (p < 0.001). Associations between TnT levels and D50-defined disease aggressiveness were generally weaker and less consistent.

INTERPRETATION: TnT was associated with measures of disease accumulation (rD50), whereas sNfL was more closely associated with disease aggressiveness (D50). Our results suggest that TnT and sNfL capture different dimensions of disease status within the D50 framework. Further longitudinal studies are needed to determine whether combining these biomarkers improves disease stratification or prognostic assessment in clinical practice and therapeutic trials.},
}

@article {pmid42494493,
year = {2026},
author = {Kennedy, J and Al Khleifat, A and King, A and Al-Sarraj, S and Al-Chalabi, A and Mitchell, JC and Troakes, C},
title = {Strenuous physical activity is associated with a younger age of amyotrophic lateral sclerosis onset in two independent cohorts.},
journal = {Brain communications},
volume = {8},
number = {4},
pages = {fcag272},
pmid = {42494493},
issn = {2632-1297},
abstract = {Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease characterized predominantly by degeneration of both upper and lower motor neurons, thought to occur due to an interplay between genetics and environmental factors. Physical activity has been suggested as a potential risk factor for ALS; however, the exact role of exercise in the onset and progression of the disease is still unclear. We assessed lifetime physical activity in two independent ALS cohorts: post-mortem brain donors from the London Neurodegenerative Diseases Brain Bank (n = 139) and patients from the Motor Neurone Disease (MND) Register of England, Wales and Northern Ireland (n = 166 cases, 196 controls). In both cohorts, highly active individuals developed ALS symptoms at a significantly younger age, 54.2 years (mean, standard deviation = 7.5) in the post-mortem cohort and 58.0 years (median, interquartile range = 15) in the MND Register, compared with 63.9 years (mean, standard deviation = 11.5) and 63.0 years (median, interquartile range = 17.5) in inactive individuals, respectively [one-way analysis of variance (ANOVA), F(2, 136) = 6.10, P = 0.003, η 2 = 0.08, 95% confidence interval (CI) 0.02-1.00 and Kruskal-Wallis, H(2) = 7.39, P = 0.02, η 2 = 0.03, 95% CI 0.003-0.12]. Cox regression showed a higher hazard of earlier onset in highly active patients [post-mortem: hazard ratio (HR) 2.84, 95% CI 1.55-5.26, P = 0.0008; MND Register: HR 2.34, 95% CI 1.30-4.23, P = 0.005]. Our findings suggest that strenuous physical activity may be associated with a significantly younger age of ALS onset, replicated in both the post-mortem and MND Register cohorts, but not with an increased risk of developing ALS. Logistic regression analysis confirmed that neither highly active [odds ratio (OR) 1.43, 95% CI 0.69-2.99, P = 0.333] nor being active (OR 1.30, 95% CI 0.72-2.37, P = 0.386) was significantly associated with ALS risk, whereas a history of head injury was (OR 1.72, 95% CI 1.03-2.88, P = 0.038). These results suggest that strenuous exercise may accelerate disease onset in predisposed individuals, while the role of head injury requires further study and the findings may in fact indicate reverse causality.},
}

@article {pmid42495327,
year = {2026},
author = {Zhan, K and Wang, Y and Lin, J and Chen, F and Fan, X and Hu, P and Wen, J and Gong, F and Zhang, N},
title = {From Simplified Pretreatment to Sensitive Analysis: An Immobilization-Free Cathodic Photoelectrochemical Assay for Sulfonylurea Herbicide Residue and Its Accumulation.},
journal = {ACS omega},
volume = {11},
number = {28},
pages = {42504-42514},
pmid = {42495327},
issn = {2470-1343},
abstract = {Sensitive and selective detection of agricultural chemicals in complex matrices necessitates streamlined workflows without performance loss. By combining the inherent high sensitivity of photoelectrochemical (PEC) analysis with the high selectivity of enzymatic recognition, an immobilization-free PEC assay for the sulfonylurea herbicide chlorsulfuron (Chs) was developed, with purification steps omitted and analytical procedure simplified. Specifically, BiOI nanoflakes (NFs)/NiO heterojunction was fabricated as a sensing platform, generating strong and stable cathodic photocurrent in the presence of dissolved O2. The catalytic reaction of acetolactate synthase (ALS) consumed O2, quenching the photocurrent response. Conversely, upon addition of the model target Chs, a representative sulfonylurea herbicide and effective inhibitor of ALS, the signal was recovered. By monitoring the photocurrent change before and after the enzymatic reaction, Chs was quantified over a linear range of 0.25-100 μg/L, with a limit of detection (LOD) of 0.16 μg/L. The assay avoids laborious probe-immobilization steps by directly adding the enzyme into the electrolyte, significantly simplifying the detection protocol. Furthermore, by omitting traditional purification procedures, the overall workflow was further optimized. The method was successfully applied to detect Chs residues in wheat powder and to evaluate its accumulation in wheat seedlings, with accuracy and reliability validated by high-performance liquid chromatography (HPLC). This work achieves highly sensitive and immobilization-free PEC analysis of Chs and offers a feasible approach for sulfonylurea herbicide detection in selected agricultural samples, with streamlined pretreatment process and enhanced analytical efficiency.},
}

@article {pmid42495582,
year = {2026},
author = {Yu, Z and Ross, JP and Rochefort, D and Li, B and Bornais, K and Chum, M and Farhan, SMK and Dion, PA and Rouleau, GA},
title = {Erratum: Consequences of the Novel ALS-Associated KIF5A Variant c.2993-6C>A for Exon 27 Splicing and Axonal Transport of SFPQ.},
journal = {Neurology. Genetics},
volume = {12},
number = {4},
pages = {e200410},
pmid = {42495582},
issn = {2376-7839},
abstract = {[This corrects the article DOI: 10.1212/NXG.0000000000200362.].},
}

@article {pmid42497114,
year = {2026},
author = {Yasuda, K},
title = {Functional constraint, not evolutionary domain expansion, is a stronger correlate of pathogenic variant burden in human RNA-binding proteins.},
journal = {Human molecular genetics},
volume = {35},
number = {15},
pages = {},
doi = {10.1093/hmg/ddag067},
pmid = {42497114},
issn = {1460-2083},
support = {23 K05147//JSPS/ ; },
mesh = {Humans ; Evolution, Molecular ; *RNA-Binding Proteins/genetics/chemistry/metabolism ; Animals ; Protein Domains/genetics ; Genetic Variation ; Amyotrophic Lateral Sclerosis/genetics ; Ribonuclease, Pancreatic/genetics ; },
abstract = {Whether evolutionary innovation predisposes genes to pathogenic variation is a fundamental question in evolutionary medicine. RBP domain family diversity correlates with neural complexity across metazoans via vertebrate-specific domain expansions. Here, we tested whether such expanded RBP domains harbor elevated pathogenic variant burden relative to evolutionarily conserved domains. We classified 2961 human RBP-encoding genes into expanded (n = 25 genes, 8 Pfam domains; vertebrate/invertebrate gene count ratio ≥ 3.0) and non-expanded control (n = 231 genes, 89 Pfam domains) groups, and integrated ClinVar pathogenic variants with gnomAD v4.1 constraint metrics. Contrary to our hypothesis, expanded domains showed lower median pathogenic variant density than non-expanded domains (P = .140, rank-biserial r = 0.180, 95% CI [-0.089, 0.444]), consistent across sensitivity analyses and count-based models. In multivariable analysis, functional constraint (pLI) was a stronger predictor of variant density than evolutionary expansion status. At the family level, no expanded domain showed significantly elevated burden; instead, the most prominent outliers were conserved non-expanded domains associated with established neurodegenerative diseases (SMN, Nop). The RNaseA family, despite 26-fold vertebrate expansion, harbored ClinVar pathogenic variants in only 1 of 15 members-fewer than expected by chance (binomial P = 0.030). The sole exception, ANG (Angiogenin), concentrates all seven ALS9-associated variants at its catalytic triad and nuclear localization signal, reflecting functional specialization rather than expansion per se. These findings indicate that evolutionary domain expansion does not confer generalized disease vulnerability in RBPs, and that pathogenic variant burden is more closely linked to functional constraint and lineage-specific subfunctionalization than to evolutionary novelty.},
}

Humans
Evolution, Molecular
*RNA-Binding Proteins/genetics/chemistry/metabolism
Animals
Protein Domains/genetics
Genetic Variation
Amyotrophic Lateral Sclerosis/genetics
Ribonuclease, Pancreatic/genetics

@article {pmid42497626,
year = {2026},
author = {Lee, JY and Hong, S and Kim, E},
title = {Soft skills education and training across the nursing continuum: A scoping review.},
journal = {Nurse education today},
volume = {166},
number = {},
pages = {107287},
doi = {10.1016/j.nedt.2026.107287},
pmid = {42497626},
issn = {1532-2793},
abstract = {AIMS: Soft skills are essential for safe and effective nursing practice, supporting communication, collaboration, and professional judgment in complex care settings. Despite their importance, new graduate nurses often struggle with core soft skills, highlighting a persistent gap between education and clinical demands. This scoping review maps current evidence on soft skills education and training for nursing students and nurses, focusing on core concepts, teaching approaches, and evaluation methods.

DESIGN: This scoping review was conducted following the PRISMA Scoping Review guidelines.

DATA SOURCES: Five databases-MEDLINE, CINAHL, Embase, Cochrane Library, and PsycINFO-were searched for studies published 2015-2025.

REVIEW METHODS: Eligible studies used experimental designs to deliver soft skill-focused education or training to nursing students or nurses. Data extraction followed the TIDieR checklist, and soft skills were classified using an adapted version of Song et al.'s framework.

RESULTS: Twenty-four studies met the inclusion criteria; most involved nursing students and quasi-experimental designs. Effective Interaction and Professionalism were the most frequently addressed skill domains. Student-focused programs emphasized interpersonal and cognitive skills, whereas nurse programs concentrated on preparedness, work management, and teamwork. Traditional lectures predominated, while participatory and emerging approaches such as virtual reality, escape rooms, and game-based learning were less common. Nurse training was typically single-session, whereas student programs were more longitudinal. Most studies relied on self-report measures and included limited follow-up.

CONCLUSIONS: A distinctive pattern emerged between students and nurses, suggesting that student-focused programs tend to emphasize foundational interpersonal skills while nurse-focused interventions are more likely to address clinically integrated competencies. This gap underscores the need to better align nursing curricula with real-world competency requirements. Educational programs on soft skills should incorporate active, learner-centered teaching strategies, rigorous evaluation methods with long-term follow-up, and validated assessment tools to better prepare nurses for contemporary healthcare demands.},
}

@article {pmid42498430,
year = {2026},
author = {Desai, KM and Thakkar, MD and Somaiya, TS and Thomas, DC},
title = {Neurodegenerative Diseases and Sleep Disorders: The Bidirectional Relationship.},
journal = {The Medical clinics of North America},
volume = {110},
number = {5},
pages = {889-905},
doi = {10.1016/j.mcna.2025.12.001},
pmid = {42498430},
issn = {1557-9859},
mesh = {Humans ; *Sleep Wake Disorders/diagnosis/complications/etiology/therapy/physiopathology ; *Neurodegenerative Diseases/complications/diagnosis/physiopathology ; Parkinson Disease/complications ; },
abstract = {Neurodegeneration is mostly irreversible and progressive. Neurodegenerative diseases (NDDs) represent a large group of disorders that have varied clinical and pathologic representations. These include Alzheimer's disease, Parkinson's disease, vascular dementia, and amyotrophic lateral sclerosis, among others. A common factor in all these NDDs is sleep disorders (SDs). NDDs and SDs are bidirectional. Screening for SDs should be an integral part of a workup of NDDs. Management of one can improve the prognosis of the other.},
}

Humans
*Sleep Wake Disorders/diagnosis/complications/etiology/therapy/physiopathology
*Neurodegenerative Diseases/complications/diagnosis/physiopathology
Parkinson Disease/complications

@article {pmid42498658,
year = {2026},
author = {Palm, A and Ekström, M and Einarsson, J and Ersson, K and Ingre, C and Kläppe, U and Lindberg, E and Ljunggren, M and Nygren, I and Sundh, J and Grote, L},
title = {Home mechanical ventilation for amyotrophic lateral sclerosis-a national study of survival and treatment trends across 27 years.},
journal = {Annals of the American Thoracic Society},
volume = {},
number = {},
pages = {},
doi = {10.1093/annalsats/aaoag219},
pmid = {42498658},
issn = {2325-6621},
abstract = {RATIONALE: Home mechanical ventilation (HMV) improves survival in Amyotrophic lateral sclerosis (ALS) and may be provided non-invasively (NIV) or invasively (IV). While NIV is guideline-recommended, the role of IV remains controversial, and data on long-term outcomes and NIV-to-IV transitions are limited.

OBJECTIVES: To examine survival across HMV strategies in people with ALS (pwALS) in Sweden over 27 years, factors associated with IV initiation, temporal trends in IV use and survival, and regional variation in IV utilisation.

METHODS: A longitudinal cohort study of pwALS in the Swedish National Registry of Ventilatory Failure (Swedevox) 1996-2022, cross-linked with national registries. Factors associated with mortality and treatment patterns were assessed using multivariable regression models.

RESULTS: Among 1,360 pwALS, initial NIV was most common (92%), followed by IV (5%) and NIV-to-IV transitions (3%). Most IV initiations were non-elective (77% vs. 18% NIV, p < 0.001). NIV-to-IV transitions occurred mainly in metropolitan areas (OR 5.11; 95% CI 2.30-11.4). Median survival differed across observed treatment pathways (p < 0.001): 1.7 years with NIV, 4.9 years with IV, and 6.5 years with NIV-to-IV. Mortality was associated with higher age (aHR 1.33 per decade; 95% CI 1.26-1.41), female sex (aHR 1.15; 95% CI 1.02-1.29), and acute initiation (aHR 1.26; 95% CI 1.08-1.47). Longer time from diagnosis to NIV initiation was associated with reduced mortality risk (aHR 0.58 per year; 95% CI 0.55-0.62). Over time, patients initiated HMV at older age with better lung function and lower PaCO2 values among those with available measurements, whereas overall survival remained unchanged.

CONCLUSION: Patients receiving IV had longer observed survival, likely reflecting the benefits of a secured airway as well as patient selection and underlying disease trajectory. Most IV initiations were unplanned. Over three decades, HMV was initiated in older patients at an earlier stage of respiratory decline, but overall survival remained unchanged. IV use increased with marked regional variation.},
}

@article {pmid42499995,
year = {2026},
author = {Nassour, J and Berberich, N and Utpadel-Fischler, D and Wächter, T and Cheng, G},
title = {A dexterous soft hand exoskeleton restores intentional grasping in individuals with severe hand impairment.},
journal = {Nature machine intelligence},
volume = {8},
number = {7},
pages = {1100-1114},
pmid = {42499995},
issn = {2522-5839},
abstract = {Soft hand exoskeletons have emerged as promising assistive devices for individuals with impaired hand function. However, most existing systems provide limited dexterity and primarily target users with moderate hand ability, leaving individuals with severe hand paralysis without effective solutions for reliable grasping of diverse objects. Here we report the translational development of a lightweight, textile-based soft robotic exoskeleton glove with wrist dorsiflexion and an active opposable and abductable thumb, designed to restore hand function in a patient with severe right-hand impairment due to amyotrophic lateral sclerosis. We followed a co-creation approach, enhancing dexterity by increasing hand articulations based on patient needs. Furthermore, to enhance the patient's sense of control, a non-invasive surface electromyography-based grasp predictor (97% sensitivity) was combined with motion data and machine learning-based error correction to compensate for weak, noisy muscle signals, compared with healthy controls (n = 15). The exoskeleton enabled the patient to grasp objects, achieve a Box-and-Blocks Test score of 5 and perform meaningful tasks, including feeding himself. We further validated the exoskeleton in patients with stroke (n = 6). While exoskeleton assistance on average reduced Action Research Arm Test scores of moderately impaired patients by 9, severely impaired patients scored 17 points higher when using the exoskeleton. These results indicate that the dexterous soft hand exoskeleton is particularly effective for individuals with severe to near-complete hand paralysis, while its utility for patients with moderate residual function is limited and task dependent.},
}

@article {pmid42500961,
year = {2026},
author = {Li, Z and Fan, J and Gong, Z and Tang, J and Yang, Y and Ding, F and Ba, L and Liu, M and Zhang, M},
title = {Cardiac autonomic dysfunction is associated with advanced stage, fast progression and poor survival in amyotrophic lateral sclerosis.},
journal = {Journal of neuromuscular diseases},
volume = {},
number = {},
pages = {22143602261472982},
doi = {10.1177/22143602261472982},
pmid = {42500961},
issn = {2214-3602},
abstract = {ObjectiveTo investigate the association of cardiac autonomic dysfunction with clinical staging and disease progression rate upon diagnosis of amyotrophic lateral sclerosis (ALS), and its impact on survival.Methods24-hour Holter was performed in 95 ALS patients at diagnosis and 39 controls. Patients were grouped by King's Clinical Staging and progression rate (ΔFS, median cut-off 0.67). Heart rate variability parameters were compared across groups. A survival-based cut-point optimization approach was used to determine the cut-off value of standard deviation of all normal-to-normal intervals (SDNN). Kaplan-Meier estimator and multivariable Cox regression analysis were used to evaluate of the effect of SDNN on survival during a median follow-up of 21.5 months.ResultsΔFS in ALS patients in King's Stage 4 upon diagnosis was faster (P=0.007) compared to that of those diagnosed in earlier stages, featuring a higher incidence of respiratory (P<0.001) and bulbar symptoms (P<0.001). In addition, ALS patients in King's Stage 4 exhibited elevated HR-min (P=0.007) and decreased RR intervals (RRI) (P=0.032), SDNN (P=0.004), and standard deviation of the averages of NN intervals in all 5-min segments (SDANN) values (P=0.020) compared to controls. Patients in the ΔFS-fast group had a higher HR-min than those in the ΔFS-slow group (P=0.013) and controls (P=0.003) and lower SDNN (P=0.018) than controls. Both Kaplan-Meier estimator (P=0.03) and multivariable Cox regression analysis (P=0.019) showed that lower SDNN (cut-off value: 111 ms) was associated with poor survival in ALS patients.ConclusionUpon diagnosis, ALS patients in King's Stage 4 and with faster disease progression demonstrated significantly diminished cardiac autonomic control. Lower SDNN was associated with poor survival in ALS.},
}

@article {pmid42501325,
year = {2026},
author = {Jia, Y and Cui, B and Liang, Y and Zhang, M and Wang, S and Wang, Y and Chen, H},
title = {Focal epilepsy expands the phenotype of FUS-associated amyotrophic lateral sclerosis.},
journal = {Epilepsia},
volume = {},
number = {},
pages = {},
doi = {10.1002/epi.70409},
pmid = {42501325},
issn = {1528-1167},
support = {82401705//National Natural Science Foundation of China/ ; 82371461//National Natural Science Foundation of China/ ; 2022YFC2503802//National Key Research and Development Program of China/ ; },
abstract = {Epileptic seizures are an exceedingly rare manifestation in classic amyotrophic lateral sclerosis (ALS). Emerging case reports suggest a potential link between ALS associated with FUS gene mutations (FUS-ALS) and seizures, expanding the disease's phenotypic spectrum. A 25-year-old man presented with a 5-month history of rapidly progressive limb weakness, atrophy, and both upper and lower motor neuron signs, consistent with ALS. Notably, he developed two types of epileptic seizures during the disease course, including focal motor seizures and focal seizures evolving to bilateral tonic-clonic seizures. Electroencephalography revealed epileptiform discharges over the right frontotemporal region. Brain [18]F-fluorodeoxyglucose positron emission tomography-computed tomography showed focal hypometabolism in the right frontal cortex. Genetic testing identified a de novo pathogenic FUS variant (c.1574C>T, p.Pro525Leu). The patient was diagnosed with FUS-ALS with comorbid focal epilepsy. Treatment with levetiracetam partially controlled the seizures, but motor function continued to deteriorate. This case highlights focal epilepsy as a comorbid feature in FUS-ALS, broadening the recognized phenotypic spectrum. Genetic testing for FUS mutations should be considered in young-onset ALS patients presenting with seizures.},
}

@article {pmid42502061,
year = {2026},
author = {Mato, S and Fukaura, J and Miyamoto, M and Watanabe, I and Naoi, T and Nakagawa, H and Saito, K},
title = {Evaluation of the Reliability and Validity of the Japanese Version of the Voice Activity and Participation Profile (VAPP-J).},
journal = {Journal of voice : official journal of the Voice Foundation},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jvoice.2026.07.010},
pmid = {42502061},
issn = {1873-4588},
abstract = {OBJECTIVES: The aim of this study was to evaluate the reliability and validity of the Japanese version of the Voice Activity and Participation Profile (VAPP).

METHODS: A total of 100 patients with voice disorders (dysphonic group) and 52 students without voice disorders (non-dysphonic group) were enrolled between October 2024 and February 2026. The psychometric properties of the Japanese VAPP were assessed, including internal consistency, concurrent and discriminant validity, interrelationships among sections, comparisons between the Activity Limitation Score (ALS) and Participation Restriction Score (PRS), and responsiveness to voice therapy. Concurrent validity was evaluated by correlations with the Voice Handicap Index (VHI).

RESULTS: Cronbach's alpha for the total score was 0.98 and remained unchanged after item deletion, indicating excellent internal consistency. VAPP total scores showed a strong positive correlation with VHI scores (r = 0.93, P < 0.001). All VAPP scores (total, section scores, ALS, and PRS) were significantly higher in the dysphonic group than in the non-dysphonic group (P < 0.001). VAPP total scores improved significantly after voice therapy (P < 0.001). Correlations among sections ranged from 0.37 to 0.86 in the dysphonic group and from 0.36 to 0.82 in the non-dysphonic group. ALS scores were significantly higher than PRS scores in the dysphonic group (P < 0.05).

CONCLUSIONS: The Japanese version of the VAPP (VAPP-J) demonstrates high reliability and validity and could be a useful tool for clinical assessment of voice disorders in Japanese populations.},
}

@article {pmid42503607,
year = {2026},
author = {Sanghai, N and Kelley, R and Lao, Y and Madlangsakay, MIR and Paul, P and Llanes-Cuesta, MA and Wang, JF and Zahedi, RP and Kong, J and Tranmer, GK},
title = {Introducing Borsantrazole: A Trifunctional Boron-Based Pyrazole That Extends the Lifespan of Amyotrophic Lateral Sclerosis Mice.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e76432},
doi = {10.1002/advs.76432},
pmid = {42503607},
issn = {2198-3844},
support = {//Research Manitoba 2017 Health Research New Investigator Operating Grant/ ; //Natural Sciences and Engineering Research Council of Canada/ ; /CAPMC/CIHR/Canada ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is considered a highly complex, heterogeneous, fatal disease with a high unmet medical need that affects multiple pathophysiological pathways and has no known singular cause. Oxidative stress, however, is implicated as a central player in the progression of ALS and other neurodegenerative diseases. To date, only two FDA-approved drugs, Edaravone, an antioxidant, and Riluzole, an antiglutamatergic, have been widely used clinically, albeit with modest effects on the clinical course of ALS disease progression. Additionally, preclinical studies of both drugs in ALS mouse models have not shown any significant survival benefit, although some abatement in disease progression is observed and translated from preclinical animal models to clinical human studies.

METHODS: Using a trifunctional boron-based drug design strategy, we have synthesized a pyrazole small molecule called Borsantrazole (BSZ) and evaluated BSZ in cell-based experiments, acute and chronic toxicity models, and the SOD1-G37R ALS mouse model. We have also evaluated untargeted global proteomic and phosphoproteomic changes induced by BSZ.

RESULTS: Borsantrazole (a small molecule that can selectively target oxidative stress) with favorable CNS drug like properties (low ER values of 0.9 and 1.0 at 1 and 10 µm, respectively, suggesting lower Pgp efflux liability and the LogD at pH 7.4 was within the range of 1.2 to 3.1, suggesting BSZ is lipophilic at pH 7.4.) shows no signs of treatment associated toxicity (acute or chronic (120 days)), significantly increases survival (whole animals, 15.1 days (p = 0.0326); males, 16.5 days; females, 13.7 days), rescued weight loss (27.1% control, 18.3% BSZ, p < 0.0001), delays symptom onset (whole animals, 24.9 days (p = 0.0011); males, 23.3 days; females, 26.4 days), delays disease onset (whole animals, 25.5 days (p = 0.0001); males, 21.1 days; females, 29.8 days) and affects global proteomic changes in the SOD1-G37R mouse model of ALS. In total, 51 proteins were found to be significantly differentially expressed (p < 0.05), including Ca3, Gan, Cplx2, Lrp4, Sqstm1, and 29 phosphorylation sites were differentially expressed and considered statistically significant, including T317 and T72 for neurofilaments light and heavy chain, respectively.

CONCLUSIONS: Herein, we report that BSZ has demonstrated a favorable safety profile and compelling proof-of-concept efficacy in a ALS mouse model and has the potential to become a disease-modifying ALS therapeutic following further clinical development. Within a broader perspective of treatments for neurodegenerative diseases, BSZ offers a new paradigm for trifunctional small molecule targeting of oxidative stress that can mitigate neuronal deterioration and serve as a potential treatment.},
}

@article {pmid42493042,
year = {2026},
author = {Shen, J and Gu, Q and Huang, Q and Chu, S and Li, R},
title = {Identification of resistance to multiple herbicides and metabolic resistance to penoxsulam in barnyardgrass (Echinochloa crus-galli).},
journal = {Pesticide biochemistry and physiology},
volume = {222},
number = {},
pages = {107231},
doi = {10.1016/j.pestbp.2026.107231},
pmid = {42493042},
issn = {1095-9939},
mesh = {*Herbicides/pharmacology ; *Herbicide Resistance/genetics ; *Echinochloa/drug effects/genetics/metabolism ; *Sulfonamides/pharmacology ; Cytochrome P-450 Enzyme System/genetics/metabolism ; Plant Proteins/genetics/metabolism ; Uridine/analogs & derivatives ; },
abstract = {Barnyardgrass (Echinochloa crus-galli) is a problematic weed in rice production, and resistance to multiple herbicides threatens sustainable management. The resistant (R) population JZWD lacks ALS target-site mutations for penoxsulam, indicating metabolic resistance. Whole-plant assays revealed that JZWD exhibited moderate resistance to penoxsulam, glufosinate ammonium and haloxyfop-P, and low resistance to quinclorac, glyphosate and halauxifen-methyl, while it was susceptible to quizalofop-p-ethyl. The synergistic effects of malathion confirmed the involvement of P450 in penoxsulam resistance. Transcriptome sequencing (RNA-Seq) of untreated and penoxsulam-treated resistant and susceptible plants revealed 25 candidate genes belonging to major detoxification enzyme families (12 cytochrome P450 monooxygenases, 3 glutathione S-transferases, 3 uridine diphosphate-dependent glycos-yltransferases, 3 ATP-binding cassette transporters and 4 peroxidase). Four core genes (CYP72A616-like, UGT83A1, CYP97B2 and PODSPC4-1) were significantly upregulated in at least two resistance-related comparisons. KEGG enrichment revealed primary metabolism pathways enriched among the upregulated genes. Technical qRT-PCR validation of the same RNA samples confirmed the RNA-Seq results for most genes. Independent biological samples revealed that CYP72A616-like was constitutively overexpressed (35.87-fold) in the R population, whereas UGT83A1, CYP97B2 and PODSPC4-1 were strongly induced by penoxsulam (8.75 to 334.92-fold). Two additional P450s (CYP71C42 and CYP734A1) were also upregulated. Among the three additional resistant populations, four representative P450 genes showed variable upregulation patterns under untreated conditions (14.79 to 160.19-fold), and all three populations were strongly induced by penoxsulam (16.25 to 945.07-fold). These results suggest that metabolic resistance mediated by P450s and other detoxification enzymes underlies multiple herbicide resistance in E. crus-galli, providing targets for resistance monitoring and sustainable weed management.},
}

*Herbicides/pharmacology
*Herbicide Resistance/genetics
*Echinochloa/drug effects/genetics/metabolism
*Sulfonamides/pharmacology
Cytochrome P-450 Enzyme System/genetics/metabolism
Plant Proteins/genetics/metabolism
Uridine/analogs & derivatives

@article {pmid42491041,
year = {2026},
author = {Wei, Z and Bai, L and Liu, X and Zhou, Y and Zheng, L and Zhang, B and Wang, L and Zou, W},
title = {Histone lactylation-mediated glycolysis-ferroptosis axis in neurological diseases.},
journal = {Frontiers in molecular neuroscience},
volume = {19},
number = {},
pages = {1820758},
pmid = {42491041},
issn = {1662-5099},
abstract = {Histone lactylation is an emerging epigenetic modification that covalently links the glycolytic metabolite lactate to histones, thereby establishing a direct link between cellular metabolic status and gene transcription programs. Recent studies have shown that this modification plays a key role in regulating cellular sensitivity to ferroptosis, forming a novel regulatory axis of "glycolysis-lactylation-ferroptosis." This article systematically reviews the biological functions of histone lactylation in the nervous system, with a focus on elucidating how it participates in the pathological processes of various neurological diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), cerebral stroke, and amyotrophic lateral sclerosis (ALS), by regulating the expression of ferroptosis-related genes. The article integrates the latest research on molecular mechanisms, explores the value of this regulatory axis as a potential biomarker for disease diagnosis and a therapeutic target, and provides an outlook on future research directions in this field.},
}

@article {pmid42492205,
year = {2026},
author = {Alizadeh, I and Darvishpour, A},
title = {Medical students' metaphors of English for Medical Purposes (EMP) teachers: Insights into educational philosophies in the Iranian context.},
journal = {Acta psychologica},
volume = {269},
number = {},
pages = {107472},
doi = {10.1016/j.actpsy.2026.107472},
pmid = {42492205},
issn = {1873-6297},
abstract = {Understanding learners' beliefs about teachers is critical for shaping English for Specific Purposes (ESP), particularly English for Medical Purposes (EMP), teaching practices in discipline-specific contexts. This qualitative descriptive study examines Iranian medical students' metaphorical conceptualizations of EMP teachers to explore how the students perceive teaching roles, authority, support, and participation in medical English classrooms. Data were collected from 144 undergraduate medical students at an Iranian medical sciences university through a sentence-completion task, in which the participants generated metaphors describing their EMP teachers. The data were analyzed using Cameron and Low's (1999) metaphor analysis framework and interpreted through Oxford et al.'s (1998) four educational philosophies of social Order, cultural transmission, learner-centered growth, and social reform. Analysis of 152 metaphors revealed that students' beliefs were predominantly aligned with learner-centered growth and cultural transmission philosophies, with the fewer reflecting the social order philosophy. No metaphors corresponded to the social reform philosophy of the teacher as a learning partner or an acceptor. While many metaphors depicted EMP teachers as supportive facilitators, they also reflected hierarchical expectations and limited learner agency. These findings offer insights into how teaching roles are constructed in EMP classrooms and provide practical implications for teachers seeking to balance disciplinary requirements with participatory teaching approaches.},
}

@article {pmid42492371,
year = {2026},
author = {Majumder, M and Borucki, DM and Chowdhury, N and Mallah, K and Tomlinson, S},
title = {Site-targeted proximal complement C3 inhibition, but not C5 blockade, attenuates neurodegeneration in a mouse model of amyotrophic lateral sclerosis: Implications for failed clinical trials.},
journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics},
volume = {23},
number = {5},
pages = {e00969},
doi = {10.1016/j.neurot.2026.e00969},
pmid = {42492371},
issn = {1878-7479},
abstract = {Complement activation contributes to amyotrophic lateral sclerosis (ALS) neuropathology, but whether motor neuron degeneration is driven by proximal or terminal activation products remains unresolved. Failed trials of C5 inhibition - ravulizumab (CHAMPION-ALS) and zilucoplan (ATHLEET/HEALEY ALS Trial), and of systemic C3 inhibition (pegcetacoplan, MERIDIAN) underscore this mechanistic gap. We compared two pharmacologically distinct inhibitors in hSOD1[G93A] mice. CR2Crry blocks complement at C3 and localizes to sites of active deposition. BB5.1, functionally equivalent to ravulizumab, selectively blocks C5a generation and membrane attack complex (MAC) assembly. Treatment began at symptom onset and continued to humane endpoint. Both agents achieved robust target engagement across spinal cord, sciatic nerve, and neuromuscular junction (NMJ). Only CR2Crry extended survival, preserved motor function, and attenuated weight loss. CR2Crry reduced microglial activation and C3 opsonization in the ventral horn, diminished macrophage infiltration, preserved sciatic nerve axonal integrity, and maintained NMJ innervation. BB5.1 failed to modify any functional or neurodegenerative pathology despite confirmed MAC suppression. Proximal C3 activation products, not C5a or MAC, are the dominant drivers of complement-mediated neurodegeneration in the hSOD1[G93A] model of ALS. Site-targeted C3 inhibition may address the mechanistic limitation underlying recent clinical trial failures and represents a translationally justified therapeutic strategy.},
}

@article {pmid42492571,
year = {2026},
author = {Tavares de Sousa, M and Crispi, F and Gomez, O and Hergert, B and Hecher, K},
title = {The carotid-subclavian artery index (CSAI) in the fetal aortic arch with classical branching and brachiobicephalic trunk in a midtrimester low risk population.},
journal = {Ultraschall in der Medizin (Stuttgart, Germany : 1980)},
volume = {},
number = {},
pages = {},
doi = {10.1055/a-2922-1435},
pmid = {42492571},
issn = {1438-8782},
abstract = {Purpose The carotid-subclavian artery index (CSAI) has shown high sensitivity and specificity for diagnosing coarctation of the aorta (CoA) in fetuses and neonates. We investigated whether variations in aortic arch (AA) branching without CoA affect CSAI by comparing fetuses with the classical pattern to those with a brachiobicephalic trunk (BBCT), the most frequent variant. Material and Methods In this prospective cohort study of 335 low-risk singleton pregnancies (19 - 22 weeks of gestation), standardized fetal echocardiography was used to assess AA branching in a sagittal view. Two blinded observers classified branching patterns and calculated CSAI. Results Adequate image quality was obtained in 262/335 (78.2%). 194/262 (74%) fetuses showed a classical pattern and 66 (25.2%) a branching variant. Furthermore, two fetuses (0.8%) due to disagreement on branching pattern. 50/66 (76.8%) fetuses with isolated BBCT were compared with 194 cases with classical AA branching pattern. 16 other variants were excluded. Interobserver agreement showed an intraclass correlation coefficient (ICC) of 0.87 (95%CI: 0.89-0.95). Mean CSAI was significantly lower in BBCT (0.71 ± 0.14) than in classical branching (1.46 ± 0.37; P < 0.001). None required cardiac intervention within two years. Conclusions Targeted fetal echocardiography showed a lower CSAI in cases with BBCT than in classical branching pattern. Future studies are warranted to assess the diagnostic impact of our findings in the setting of suspected CoA. Zielsetzung: Der Carotis-Subclavian-Artery-Index (CSAI) wird in der Diagnostik der Aortenisthmusstenose (CoA) eingesetzt. Wir untersuchten, ob der CSAI bei Feten mit Varianten der Aortenabgänge eine Rolle spielt und verglichen diesen mit Werten bei Aortenbögen mit klassischen Abgängen. Material und Methoden: In dieser prospektiven Kohortenstudie wurden 335 Einlingsschwangerschaften mit niedrigem Risiko zwischen der 19. und 22. Schwangerschaftswoche mittels standardisierter fetaler Echokardiografie untersucht. Der Aortenbogen wurde in sagittaler Ebene dargestellt. Zwei voneinander unabhängige Untersuchende beurteilten verblindet das Abgangsmuster und berechneten den CSAIErgebnisse: Eine ausreichende Bildqualität konnte bei 262 von 335 Fällen (78,2 %) erzielt werden. 194/262 (74 %) Feten zeigten ein klassisches Abgangsmuster, 66 (25,2 %) eine Variante. Bei zwei Feten (0,8 %) bestand Uneinigkeit über das Abgangsmuster. 50/66 (76,8 %) Feten mit isoliertem BBCT wurden mit den 194 Fällen mit klassischem Abgang verglichen; 16 weitere Varianten wurden ausgeschlossen. Die Interobserver-Übereinstimmung zeigte einen Intraklassen-Korrelationskoeffizienten (ICC) von 0,87 (95 %-KI: 0,89-0,95). Der mittlere CSAI war bei BBCT signifikant niedriger (0,71 ± 0,14) als bei klassischem Abgang (1,46 ± 0,37; p < 0,001). Kein Kind benötigte innerhalb von zwei Jahren eine kardiale Intervention. Schlussfolgerung: Die gezielte fetale Echokardiografie zeigte einen signifikant niedrigeren CSAI bei Feten mit BBCT im Vergleich zu Feten mit klassischem Aortenbogenabgang. Weitere Studien sind erforderlich, um die diagnostische Bedeutung dieser Befunde im Kontext eines Verdachts auf Aortenisthmusstenose zu klären.},
}

@article {pmid42484778,
year = {2026},
author = {Lill, CM and Homann, J and Ohlei, O and Smith-Byrne, K and Viallon, V and Huerta, JM and Artaud, F and Zhao, Y and Britten, A and Deecke, L and Dobricic, V and Mokoroa, O and Guevara, M and Petrova, D and Trupp, M and Sabin, J and Gröninger, M and Colorado-Yohar, SM and Alonso-Martin, S and Cabrera-Castro, N and Groppa, S and Robinson, O and Hansen, J and Eriksson, S and Sieri, S and Jimenez, A and Tong, TYN and Kaaks, R and Severi, G and Travis, R and Wareham, N and Benedet, AL and Zetterberg, H and Franke, A and Elbaz, A and Bertram, L and Vermeulen, R and Middleton, L and Masala, G and Sacerdote, C and Peters, S and Katzke, V and Ferrari, P and Gunter, MJ and Riboli, E},
title = {EPIC4ND-European Prospective Investigation into Cancer and Nutrition follow-up for neurodegenerative diseases.},
journal = {European journal of epidemiology},
volume = {},
number = {},
pages = {},
pmid = {42484778},
issn = {1573-7284},
support = {#008994//Michael J Fox Foundation/ ; JPND2021-650-289//EU Joint Programme - Neurodegenerative Disease Research/ ; LI 2654/3-1//Deutsche Forschungsgemeinschaft/ ; LI 2654/4-1 (Heisenberg)//Deutsche Forschungsgemeinschaft/ ; INTRAIBS-2020-06//Instituto de Investigación Biosanitaria ibs.GRANADA/ ; },
abstract = {The 'European Prospective Investigation into Cancer and Nutrition' cohort (EPIC) is a prospective study including ~ 520,000 participants recruited across Europe (1991-2000) with in-depth baseline data on nutritional, lifestyle, medical, and anthropometric variables, and baseline blood samples. Here we introduce EPIC4ND, a case-cohort study within EPIC designed to identify biomarkers predicting a future onset of dementia, Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). EPIC4ND comprises 6415 initially non-diseased participants (aged 35-80 years, mean age at baseline: 54 ± 9, 64% women) including 1899 incident cases with up to 30 years of follow-up and data on at least one omics domain available from pre-disease blood samples. EPIC4ND includes 4604 subcohort members (4441 non-cases and 163 incident cases) and 1811 additional incident cases ascertained from the broader EPIC cohort. Among the incident cases, there are 1190 dementia cases (818 AD), 610 PD cases, and 199 ALS cases. Additionally, 72 prevalent PD cases and 118 incident Parkinsonism cases are available for comparison. Molecular data generated encompass proteomics, genome-wide DNA methylation, and SNP genotyping with 4127 EPIC4ND participants (including 1635 incident cases) having data on all three domains. Smaller studies include data on metals, metabolites, and environmental chemicals, while ongoing efforts focus on ultrasensitive targeted biomarker measurements and small RNA sequencing. Genome-wide association studies and analyses of epidemiological risk factors validate the dataset by confirming many known risk factors. Leveraging these extensive pre-disease multi-layered omics data offers a unique opportunity to identify biomarker signatures predicting neurodegenerative diseases and to explore their interplay with epidemiological risk factors.},
}

@article {pmid42485154,
year = {2026},
author = {Cohn, B and Theoryn, T and Sommerland, O and Murali, P and Yu, JH and Anderson, K and McWalter, K and Johnson, B and Doherty, D and Bamshad, MJ and MacDuffie, KE},
title = {Capturing Perceived Utility from Qualitative Studies of Genomic Sequencing: Translating a Conceptual Model into a Working Codebook.},
journal = {AJOB empirical bioethics},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/23294515.2026.2691711},
pmid = {42485154},
issn = {2329-4523},
abstract = {INTRODUCTION: As genomic sequencing (GS) is integrated into clinical medicine, understanding how patients and families perceive its utility is critical. Conceptual models for perceived utility have been developed, however, direct application of such models to independently-collected qualitative data remains rare. To fill this gap, we translated a comprehensive model of perceived utility (Smith et al. 2022) into a codebook and revised it via application to a qualitative dataset capturing parent-reported utility of GS.

METHODS: Using the domains and subdomains from Smith et al.'s conceptual model, we developed an initial codebook. We tested the derived codebook on data from 40 interviews with parents of children enrolled in SeqFirst, a research study offering GS for critically ill newborns in the neonatal intensive care unit and young children (<3 years) with unexplained developmental differences. Four coders independently applied the codebook. We addressed ambiguities through memoing and refined definitions via study team consensus.

RESULTS: The resulting codebook includes all five of Smith et al.'s (2022) domains: clinical, emotional, behavioral, cognitive, and social utility. We renamed and relocated several subdomains to add additional clarity in coding decisions, and developed definitions for all subdomain codes. The final codebook is included as a resource for future research.

CONCLUSIONS: This study translates a conceptual framework of perceived utility of GS into a practical codebook for qualitative research. Our intent is to facilitate conceptually-grounded, replicable coding across studies and settings, supporting both inductive and deductive analyses. Applying this codebook can enhance comparability of qualitative findings, inform refinement of conceptual models, and guide the further development of patient-centered measures of GS utility.},
}

@article {pmid42485353,
year = {2026},
author = {Vanunu, M and Zecharia, N and Dror, O and Omer, Y and Brukental, H and Harel-Beja, R and Hatib, K and Azoulay-Shemer, T and Holland, D and Shtienberg, D and Bahar, O},
title = {Identification of an Almond Cultivar Resistant to Xylella fastidiosa subsp. fastidiosa and Insights into Host-Specific Bacterial Behavior.},
journal = {Plant disease},
volume = {},
number = {},
pages = {},
doi = {10.1094/PDIS-02-26-0369-RE},
pmid = {42485353},
issn = {0191-2917},
abstract = {Xylella fastidiosa (Xf) is a xylem-limited bacterial pathogen causing disease in a variety of important agricultural crops, including almonds. Almond leaf scorch (ALS) disease was first identified in Israel in 2017 and is associated with the subspecies X. fastidiosa subsp. fastidiosa (Xff) sequence type 1. Currently, there is no effective means to cure infected almond trees, and ALS management relies primarily on uprooting infected trees and reducing vector populations, yet these methods are only moderately effective. Thus, identifying resistant almond genotypes is a critical goal for developing durable ALS management strategies. In this study, we utilized three complementary methods to evaluate resistance among various almond genotypes: 1) grafting onto Xff-infected trees; (2) mechanically inoculating young trees' stems; and (3) mechanically inoculating individual leaves. In a field-based grafting experiment involving seven genotypes, 'Lauranne' exhibited strong resistance to Xff infection compared to the other tested cultivars. In subsequent two experiments, we monitored Xff migration and colonization in 'Lauranne', a susceptible almond cultivar ('Um ElFahem'), and a non-host plant, plum. Although Xff was able to migrate and replicate within 'Lauranne', it did so at significantly lower levels and with slower progression rate. Histological analysis at the leaf level further confirmed that the number of Xff-colonized xylem vessels was substantially reduced in 'Lauranne' relative to the susceptible cultivar. These findings highlight 'Lauranne' as a promising resistant cultivar and underscore the importance of identifying resistance mechanisms in almonds. Incorporating resistant genotypes (such as 'Lauranne') into breeding programs may offer a durable and sustainable solution to manage ALS in the future.},
}

@article {pmid42487057,
year = {2026},
author = {Adams, J},
title = {"Hermeneutic burden" and clinical responsibility: a response to Sparrow et al. on explanation and machine learning.},
journal = {Monash bioethics review},
volume = {},
number = {},
pages = {},
pmid = {42487057},
issn = {1836-6716},
abstract = {This paper critically reviews Sparrow et al.'s notion of the "hermeneutic burden" placed upon clinicians by the demand for explainable artificial intelligence (XAI) in the context of adaptive machine learning (ML) systems. While Sparrow et al. highlight important additional labour that may be required of clinicians, this response argues that framing explanation primarily in terms of such a burden obscures its overall ethical significance. This paper therefore offers a supplementary account of the interpretive work associated with XAI in medicine that places it within existing models of the patient-clinician relationship. In particular, Emanuel and Emanuel's influential typology consisting of four models of the patient-physician relationship is used to extract possible justifications for the responsibility to grasp and explain not only patients' values and conditions but also ML outputs. This allows us to distinguish between 'hermeneutic burden' and 'hermeneutic responsibility' and emphasise that explanation in medicine is not an incidental task but part of a clinician's professional role, particularly on 'interpretive' and 'deliberative' models. The paper thus argues that viewing explanation as a hermeneutic responsibility linked to patient autonomy clarifies the ethical significance of XAI in terms of both the grounds and scope of clinicians' responsibilities. At its core, the ethical challenge raised by XAI in clinical practice concerns not only the burdens it may impose on clinicians but also the evolution of clinicians' traditional interpretive duties in the novel context of ML-mediated care.},
}

@article {pmid42487076,
year = {2026},
author = {Picchiarelli, G and Wienand, A and Megat, S and Hutten, S and Aly, A and Been, M and Weber, I and Bonanno, A and Mishra, N and Sternburg, E and Cauchy, P and Dieterle, S and Catinozzi, M and Lobo-Mancheno, J and Walgrave, H and Demais, V and Hener, P and Kessler, P and Tzeplaeff, L and Huebers, A and Zeuschner, D and Rosenbohm, A and Ludolph, AC and Boutillier, AL and Boeckers, T and Dormann, D and Demestre, M and Sellier, C and Lagier-Tourenne, C and Storkebaum, E and Dupuis, L},
title = {FUS controls muscle differentiation through phase separation-mediated recruitment of the transcription factors MEF2 and ETV5.},
journal = {The EMBO journal},
volume = {},
number = {},
pages = {},
pmid = {42487076},
issn = {1460-2075},
support = {ANR-16-CE92-0031,ANR-19-CE17-0016,ANR-20-CE17-0008,ANR-21-CE17-0039//Agence Nationale de la Recherche (ANR)/ ; ANR-10-IDEX-0002//Agence Nationale de la Recherche (ANR)/ ; ANR-20-SFRI-0012//Agence Nationale de la Recherche (ANR)/ ; ANR-24-INBS-0005 FBI BIOGEN//Agence Nationale de la Recherche (ANR)/ ; #23646 #18280//French Muscular Dystrophy Association (AFM)/ ; Coup d'élan 2019//Fondation Bettencourt Schueller (Bettencourt Schueller Foundation)/ ; DEQ20180339179//Fondation pour la Recherche Médicale (FRM)/ ; rare disease award 2019//AXA Research Fund (FONDS AXA POUR LA RECHERCHE)/ ; 2016,2021//Association pour la Recherche sur la Sclérose Latérale Amyotrophique et autres Maladies du Motoneurone (ARSLA)/ ; 2235//ALS Association (ALSA)/ ; 946876//Muscular Dystrophy Association (MDA)/ ; Open Competition ENW-M//Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO)/ ; 442698351//Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO)/ ; 497669232//Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO)/ ; ERC-2017-COG 770244//EC | European Research Council (ERC)/ ; ClueDol//region grand est/ ; 84012490//EC | ERDF | Interreg/ ; },
abstract = {FUS is an RNA-binding protein mutated in amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by progressive muscle weakness. We show in this work that a heterozygous knock-in mutation in the mouse Fus gene leads to cell-autonomous ultrastructural defects in skeletal muscle, with disruption of sarcomeres and mitochondria. Studies in mouse and Drosophila models demonstrate an evolutionarily conserved cell-autonomous function of FUS in muscle development. Mechanistically, FUS is required for the transcription of MEF2 target genes, binds to the promoter of genes bound by ETS transcription factors, in particular ETV5, and co-activates the transcription of MEF2-dependent genes with ETV5. FUS phase-separates with ETV5 and MEF2A, and stimulation of MEF2-dependent transcription by FUS is dependent upon its phase separation properties. Finally, Etv5 haploinsufficiency exacerbates muscle weakness and atrophy in Fus knock-in mice. Our findings establish a key role for FUS in skeletal muscle differentiation through its phase separation-dependent recruitment of ETV5 and MEF2, defining a novel pathway compromised in FUS-ALS.},
}

@article {pmid42487414,
year = {2026},
author = {Bruce, AJ and Menapace, DC},
title = {Invited Commentary on: Gaebe et al's "Effectiveness and Safety of Extracellular Vesicle-Based Therapies for Non-Surgical Facial Rejuvenation: A Systematic Review": Extracellular Vesicles in Aesthetic Medicine: Promise Requires Proof.},
journal = {Facial plastic surgery & aesthetic medicine},
volume = {},
number = {},
pages = {26893614261466120},
doi = {10.1177/26893614261466120},
pmid = {42487414},
issn = {2689-3622},
}

@article {pmid42489267,
year = {2026},
author = {Xie, Q and Zhu, Y and Jiang, W and Xie, H and Li, Y and Hu, M and Li, K and Yu, H and Pan, Y and Jiang, C and Song, X and Fan, D and Deng, B},
title = {A Blood-Derived Factor Rescues ALS: Platelet Factor 4 Activates OPTN-Dependent Autophagy to Clear SOD1 Aggregates Independently of PINK1.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e76778},
pmid = {42489267},
issn = {2198-3844},
support = {ZCLY24H0903//Natural Science Foundation of Zhejiang Province/ ; 2025L-C7//Hebei Key Laboratory of Neurology/ ; },
abstract = {Peripheral factors that systemically regulate amyotrophic lateral sclerosis (ALS) have remained elusive-until now. Here, by integrating population-scale epidemiology with mechanistic dissection, we identify platelet factor 4 (PF4) as the central driver of a circulating neuroprotective axis that restores proteostasis and rescues ALS. In a prospective cohort of >500 000 UK Biobank participants, platelet indices were strongly associated with ALS risk, and serum PF4 levels were significantly reduced in ALS patients. Systemic administration of recombinant PF4 in hSOD1[G93A] mice produced dramatic therapeutic effects: extended survival, preserved motor function, attenuated neuroinflammation, and reduced neuromuscular junction denervation. Remarkably, this efficacy appears pathology-selective-robust in SOD1-driven models but shows no observable effect in TDP-43 or C9orf72 ALS models. Mechanistically, PF4 achieves what few molecules can: it engages the cell surface receptor LRP1 to activate the TBK1-OPTN signaling axis, restoring impaired autophagic flux through a PINK1/Parkin-independent pathway requiring ATG7, establishing a previously unrecognized peripheral platelet-autophagy-neuron axis that facilitates the co-clearance of pathological SOD1 aggregates and damaged mitochondria. This study unveils PF4 as a first-in-class circulating autophagy regulator with therapeutic potential in ALS. Beyond identifying a candidate biomarker and drug lead, it reveals that systemic factors can directly engage central proteostatic machinery-opening a new frontier for ALS therapy.},
}

@article {pmid42489904,
year = {2026},
author = {Jellinger, KA},
title = {Psychiatric disorders in amyotrophic lateral sclerosis: a short note.},
journal = {Journal of neural transmission (Vienna, Austria : 1996)},
volume = {},
number = {},
pages = {},
pmid = {42489904},
issn = {1435-1463},
abstract = {Traditionally, amyotrophic lateral sclerosis (ALS) has been defined as a rapidly progressive neurodegenerative disorder that affects the large motor neurons of the brain and spinal cord. The assumption that ALS is a pure motor disorder has been increasingly challenged by accumulating evidence about an association between ALS and psychiatric disorders. They often precede the onset of motor symptoms or psychoses; hallucinations and schizophrenia may occur as concomitant changes. These non-motor disorders have a close relationship with disease onset or may be related to a larger framework of neuronal network disruptions in motor neuron disorders. The link between ALS and schizophrenia was supported by substantial genetic correlations associating the C9orf72 gene expansion with psychiatric disorders. The genetic correlation between ALS and schizophrenia was estimated to be 14.3% with frequent polygenic risk scores. Increased psychotic symptoms in C9orf72 carriers correlate with atrophy in a distributed cortical and subcortical network that includes multiple cerebral regions. ALS kindreds often present higher rates of psychiatric illnesses, and early schizophrenia is significantly associated with the development of ALS. Further studies should attempt to delineate the risk of psychiatric disorders in C9orf72 kindreds to aid in clinical decision making and genetic counseling, through collaborations between neurology and psychiatry.},
}

@article {pmid42480869,
year = {2026},
author = {Petro, TM and Pattee, GL and Esmael, A and Agarkova, IV and Dunigan, DD and Chiodo, F and De Castro, C and Van Etten, JL},
title = {Macrophage responses to and elevated antibody levels against Chlorovirus ATCV-1 in ALS patients.},
journal = {Antiviral research},
volume = {253},
number = {},
pages = {106491},
doi = {10.1016/j.antiviral.2026.106491},
pmid = {42480869},
issn = {1872-9096},
abstract = {Acanthocystis turfacea chlorella virus 1 (ATCV-1) is a giant virus that is part of the human oral microvirome. Previously we showed that ATCV-1 infects mouse macrophages, stimulates production of inflammatory cytokines, and accelerates motor neuron disease in the Amyotrophic Lateral Sclerosis (ALS) model SOD1-G93A transgenic mice. This, coupled with significantly elevated levels of serum IgG1 antibody to ATCV-1 in ALS patients compared with healthy controls, suggests involvement of ATCV-1 in ALS. Herein, using serum and CSF from a different ALS cohort we again show elevated antibodies to ATCV-1 in ALS patients compared with healthy controls. To assess ATCV-1 in human macrophages, we challenged immature (IMM), M0, M1, and M2 human THP-1 macrophage cells containing an Interferon Stimulated Response Element (ISRE) promoter-reporter with ATCV-1 or its Major Capsid protein (MCP) glycans. ATCV-1 infected M1 THP-1 to a greater degree than IMM, M0, or M2 THP-1. The initial high ISRE-promoter activity of M1 THP-1 was suppressed by the MCP-Glycans of ATCV-1. M0, but not IMM or M2 THP-1 produced IL-6 in response to ATCV-1 or its MCP-glycan, while high levels of IL-6 from unchallenged M1 THP-1 increased further by ATCV-1 or its MCP glycan. In contrast, ATCV-1 or its MCP-Glycan significantly reduced the high levels of IL-10 produced by M2 THP-1. Thus, antibody to ATCV-1 in ALS patients and the susceptibility of human M1 macrophages to ATCV-1 infection with boosted inflammatory cytokine and diminished anti-inflammatory cytokine production suggest that ATCV-1 may contribute to ALS motor neuron disease.},
}

@article {pmid42481428,
year = {2026},
author = {Fukumoto, T and Osaki, Y and Hanada, K and Fujita, K and Kaji, R and Izumi, Y},
title = {The Anterior Belly of the Digastric Muscle as a Novel Target for Needle Electromyography in Amyotrophic Lateral Sclerosis.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70354},
pmid = {42481428},
issn = {1097-4598},
support = {JPMH23FC1008//Ministry of Health, Labour and Welfare, Japan, through the Research Program on Rare and Intractable Diseases/ ; },
abstract = {INTRODUCTION/AIMS: Needle electromyography (EMG) in the bulbar region aids in the diagnosis of amyotrophic lateral sclerosis (ALS) but remains technically challenging. The genioglossus muscle (GM) is commonly examined; however, pain and poor relaxation may limit its evaluation. The trapezius is an alternative target but is innervated by the spinal accessory nerve. We investigated the utility of the anterior belly of the digastric muscle (ABDM), innervated by the trigeminal nerve, for bulbar EMG evaluation.

METHODS: In this unblinded, prospective observational study, consecutive patients with suspected ALS underwent needle EMG of the ABDM, GM, masseter muscle (MM), and trapezius. Relaxation levels, EMG abnormalities, and pain (100-mm visual analog scale [VAS]) were assessed.

RESULTS: Twenty-seven clinically diagnosed ALS patients were analyzed. Relaxation was better in the ABDM than in the GM (p < 0.001) and comparable to that in the MM and trapezius. Fasciculation potentials were detected more often in the ABDM (52%) than in the GM (0%) and MM (22%; p = 0.039) and were comparable to the trapezius (59%). Chronic denervation occurred at similar frequencies across muscles (33%-59%). The combination of abnormal spontaneous activity and chronic denervation was most frequent in the ABDM (37%). Pain was lower with the ABDM (median VAS score of 21) than with the GM (28; p = 0.0052) and MM (32; p < 0.001) and was similar to the trapezius (23).

DISCUSSION: The ABDM may be a practical additional target for bulbar EMG in ALS, with favorable relaxation, lower pain, and potentially improved electrodiagnostic yield.},
}

@article {pmid42481875,
year = {2026},
author = {Sahin, U and Firat-Karalar, EN},
title = {The centrosome-cilium-centriolar satellite axis in neurodegenerative diseases.},
journal = {EMBO reports},
volume = {},
number = {},
pages = {},
pmid = {42481875},
issn = {1469-3178},
support = {101078097//EC | H2020 | PRIORITY 'Excellent science' | H2020 European Research Council (ERC)/ ; 3336//European Molecular Biology Organization (EMBO)/ ; 3622//European Molecular Biology Organization (EMBO)/ ; YIP//European Molecular Biology Organization (EMBO)/ ; (SU PREG)//Sabanci University President's Research/ ; },
abstract = {Neurodegenerative diseases (NDDs), including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and hereditary ataxias, remain major global health challenges with limited therapeutic options. Although clinically and genetically diverse, these diseases share extensively studied cellular and molecular hallmarks, including protein aggregation, impaired proteostasis, cytoskeletal abnormalities, altered energy metabolism, nucleic acid damage, and chronic inflammation. Emerging evidence indicates that dysfunction of the centrosome-cilium-satellite axis intersects with these established pathways in disease- and cell type-specific contexts. This axis, composed of centrosomes, primary cilia, and centriolar satellites, coordinates cytoskeletal organization, ciliary signaling, trafficking, proteostasis, and stress responses and acquires specialized functions in neurons that support polarity, connectivity, and long-term maintenance. In this review, we outline the structure, function, and neuronal specializations of the centrosome-cilium-satellite axis, then examine how its dysfunction has been reported in neurodegenerative disease models. We also discuss centriolar satellites as regulators of centrosome and cilium biology whose disease-specific roles in classical NDDs remain comparatively underexplored, with insights from Huntington's disease and schizophrenia. Finally, we discuss therapeutic strategies aimed at restoring axis structure and dynamics, modulating ciliary signaling, and correcting disease-linked genetic or transcript-level defects, emphasizing mechanism-based approaches that require validation in disease-relevant models. Together, the centrosome-cilium-satellite axis provides an emerging framework for understanding context-dependent organelle dysfunction in neuronal vulnerability and neurodegeneration.},
}

@article {pmid42482399,
year = {2026},
author = {Merrill, K and Giesel, BP and Barclay, JS},
title = {Assessing Involvement and Training of Academic Palliative Care Programs in the Care of Patients with Sickle Cell Disease: A Nationwide Survey.},
journal = {Journal of palliative medicine},
volume = {},
number = {},
pages = {10966218261472552},
doi = {10.1177/10966218261472552},
pmid = {42482399},
issn = {1557-7740},
abstract = {BACKGROUND: Despite high symptom burden and limited lifespan associated with sickle cell disease (SCD), specialty palliative care (PC) services remain underutilized in this marginalized population.[1,2] The extent of routine involvement, barriers to care, and training in the care of SCD patients at academic PC programs in the United States has not been quantified.

OBJECTIVE: To assess PC involvement and training in SCD care, identify barriers to access, and inform integration strategies.

DESIGN/SETTING: An anonymous Qualtrics survey, developed through literature review and expert panel, was emailed to 180 palliative medicine fellowship program directors or surrogates (June 18-July 25, 2025) in the United States. The survey included demographics, program practices regarding SCD and other chronic conditions (cystic fibrosis, amyotrophic lateral sclerosis, and chronic nonmalignant pain), frequency of routine SCD education, and perceived barriers to providing care to these patients.

RESULTS: Fifty-one responses were received (28.3% response rate). Only 37% of programs routinely care for SCD patients (31.5% inpatient only, 10.5% outpatient, 58% both). Among these, 68% regularly prescribed opioids. Programs not routinely involved reported exceptions for patients with limited prognosis, comorbidities such as active cancer, or imminent end-of-life needs. The most common reported barriers to seeing patients with SCD were lack of outpatient resources (46%) and staffing constraints (44%). Free-text responses cited limited referrals, competing specialty ownership (hematology), institutional restrictions, and scope-of-practice limitations. Only 38% of programs included SCD in their fellowship curriculum, and 20% offered routine training for all PC team members.

CONCLUSIONS: Fewer than half of academic PC programs routinely care for SCD patients, and most programs lack formal SCD training. Institutional and systemic barriers limit access, highlighting the need for resources and education to expand PC integration into SCD care. There is a need for consensus guidelines stratifying PC involvement in SCD patients.},
}

@article {pmid42482414,
year = {2026},
author = {Topsøe-Jensen, SK and Wingren, CJ and Villa, C},
title = {Forensic bruise documentation with alternate light sources: Preliminary observation on deceased individuals in a routine illuminated autopsy setting.},
journal = {Journal of forensic sciences},
volume = {},
number = {},
pages = {},
doi = {10.1111/1556-4029.70404},
pmid = {42482414},
issn = {1556-4029},
abstract = {Alternate light sources (ALS) have been suggested to improve bruise visibility for medicolegal evaluations. Previous studies have recommended darkened conditions; however, this does not reflect real-life autopsy settings, where multiple examinations are conducted simultaneously and turning off the lights is neither practical nor safe. This study evaluated the use of ALS for documenting bruises under normal lighting conditions without altering the autopsy setup. We photographed 161 bruises (99 recent, 62 non-recent) using CrimeLite® AUTO (Foster+Freeman) under common white light (CWL), violet ALS with 415 nm long-pass (VLP), violet ALS with 415 nm band-pass (VBP), and blue ALS with 445 nm long-pass (BLP). Bruises were classified as recent or non-recent based on the presence of yellow coloration. Visibility was scored using a "modified" Bruise Visibility Scale (BVS), and surface area was measured. Observer variability was assessed using Cohen's kappa (κ) and intraclass correlation coefficients (ICC); logistic and Cox regression analyses were performed to evaluate BVS and size across lighting sources. We found that ALS did not enhance bruise visibility compared to CWL. VBP and BLP reduced visibility, while VLP showed occasional improvements but without statistical significance. Surface area measurements indicated that VLP visualizes bruises with larger dimensions than under CWL, whereas BLP and VBP did not. Observer agreement for the four BVS categories yielded κ values ranging from moderate to substantial, while ICCs showed excellent agreement for surface-area measurements for most light sources. Despite its limitations, the study suggests that ALS, particularly VLP, may have potential utility for bruise documentation under normal lighting conditions.},
}

@article {pmid42482658,
year = {2026},
author = {Wang, J and Wang, Y and Yang, T and Yan, X and Luo, J and Wu, S and Tong, J and Zhao, M and Yang, G},
title = {Sex-associated differences in routine inflammatory markers and neuromuscular ultrasound measurements in amyotrophic lateral sclerosis: a retrospective cross-sectional study.},
journal = {Annals of medicine},
volume = {58},
number = {1},
pages = {2703317},
pmid = {42482658},
issn = {1365-2060},
mesh = {Humans ; Female ; Male ; Cross-Sectional Studies ; Retrospective Studies ; *Amyotrophic Lateral Sclerosis/blood/diagnostic imaging/physiopathology ; Middle Aged ; Biomarkers/blood ; Ultrasonography ; Aged ; Sex Factors ; Disease Progression ; Blood Sedimentation ; *Inflammation/blood ; Adult ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder with substantial clinical heterogeneity. Systemic inflammatory markers and neuromuscular ultrasound measurements have both been studied in ALS, but their sex-associated differences within ALS cohorts remain incompletely characterized.

OBJECTIVE: To examine sex-associated differences in routine inflammatory markers and neuromuscular ultrasound measurements in patients with ALS, and to determine whether these differences persisted after adjustment for available clinical and anthropometric variables.

METHODS: In this retrospective cross-sectional study, 135 patients with ALS were included. Routine inflammatory markers, including neutrophils, monocytes, lymphocytes, platelets, and erythrocyte sedimentation rate (ESR), were analyzed alongside quantitative neuromuscular ultrasound measurements. Between-sex comparisons were performed, and false discovery rate correction was applied to account for multiple testing. Multivariable linear regression analyses were performed with adjustment for age, disease duration, body mass index (BMI), ALSFRS-R total score, FVC% predicted, smoking status, hypertension, and diabetes.

RESULTS: Female patients showed lower ALSFRS-R total scores and higher estimated progression rates in unadjusted comparisons, whereas pulmonary function variables did not differ significantly between sexes. After FDR correction, estimated progression rate, neutrophil count, monocyte count, ESR, and masseter muscle thickness remained significantly different between sexes, while the ALSFRS-R difference was borderline significant. In fully adjusted models, female sex was associated with lower neutrophil count, monocyte count, and median nerve cross-sectional area; biceps brachii thickness showed a less stable association after sensitivity analysis. An exploratory secondary analysis showed lower rectus femoris cross-sectional area during thigh-lift in female patients after full adjustment. In the spline sensitivity analysis, this association remained statistically significant but was interpreted cautiously because it was not present in the earlier adjustment models.

CONCLUSIONS: Selected routine inflammatory markers and neuromuscular ultrasound measurements differed between male and female patients within this ALS cohort. These findings support consideration of sex and anthropometric context, including body size, when interpreting inflammatory markers and ultrasound-based structural measurements. In the absence of healthy controls, the observed ultrasound differences cannot be attributed specifically to ALS-related biology. Studies with healthy controls, longitudinal functional outcomes, body-composition assessment, and independent multicenter cohorts are needed to clarify the disease-specific and prognostic relevance of these observations.},
}

Humans
Female
Male
Cross-Sectional Studies
Retrospective Studies
*Amyotrophic Lateral Sclerosis/blood/diagnostic imaging/physiopathology
Middle Aged
Biomarkers/blood
Ultrasonography
Aged
Sex Factors
Disease Progression
Blood Sedimentation
*Inflammation/blood
Adult

@article {pmid42483382,
year = {2026},
author = {Joy, B},
title = {Is the stroke-COVID link solid? A critical analysis of Aghamiri et al.'s research methodology and findings.},
journal = {Journal of family medicine and primary care},
volume = {15},
number = {5},
pages = {2177-2178},
pmid = {42483382},
issn = {2249-4863},
}

@article {pmid42484074,
year = {2026},
author = {Carberry, N and Wuu, J and Benatar, M},
title = {SOD1-lowering therapy for patients with wildtype SOD1-ALS: a case report.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-3},
doi = {10.1080/21678421.2026.2705142},
pmid = {42484074},
issn = {2167-9223},
abstract = {Background and Objectives: To describe clinical and biomarker experience using an SOD1 antisense oligonucleotide (ASO) in a patient with non-SOD1 amyotrophic lateral sclerosis (ALS). Methods: Case report. Results: In a 72-year-old male with non-SOD1 ALS, rapid decline on the ALS functional rating scale revised (ALSFRS-R) and a rise in serum neurofilament light chain (NfL) concentration were observed following 3 loading doses of an SOD1 ASO before the patient succumbed to disease. The time from symptom onset to death was 9 months. Discussion: While treatment was initiated relatively late (∼7 months) after symptom onset and follow-up duration was short, the observed increase (as opposed to a reduction) in serum NfL and accompanying rapid functional decline, suggest the lack of a therapeutic effect in someone with fast progressing non-SOD1 ALS.},
}

@article {pmid42484509,
year = {2026},
author = {Tsujisawa, Y and Takahashi-Iwata, I and Yabe, I and Mukaino, M and Shibamoto, I},
title = {An investigation of factors associated with speech intelligibility in patients with amyotrophic lateral sclerosis: Integrating acoustic and lingual motor measures.},
journal = {Clinical linguistics & phonetics},
volume = {},
number = {},
pages = {1-20},
doi = {10.1080/02699206.2026.2704600},
pmid = {42484509},
issn = {1464-5076},
abstract = {Speech intelligibility in amyotrophic lateral sclerosis (ALS) progressively declines, but contributing clinical factors may vary according to disease presentation and extent of bulbar involvement. This study examined factors associated with intelligibility in three ALS groups: spinal-onset, spinal-onset with bulbar involvement (spinal + bulbar), and bulbar-onset. Speech intelligibility (visual analogue scale), hypernasality, maximum tongue pressure, respiratory function (%VC and FEV1/FVC), and second formant (F2) transition measures (transition duration and excursion) were evaluated. Exploratory two- and three-dimensional visualisations were used to examine interrelationships among variables, and regression analyses were conducted in groups with sufficient sample size. In spinal-onset ALS, only hypernasality was associated with intelligibility. In bulbar-onset ALS, both tongue pressure and hypernasality were significantly associated with intelligibility, while preserved F2 excursion showed an additional trend towards better intelligibility. In the spinal + bulbar group, descriptive findings suggested that reduced tongue pressure and increased hypernasality were associated with lower intelligibility. These findings suggest that speech intelligibility in ALS is influenced by different combinations of bulbar-related impairments depending on clinical presentation and extent of bulbar involvement. In particular, tongue strength, velopharyngeal function, and residual tongue mobility may be relevant to intelligibility outcomes with bulbar involvement. Combined evaluation of these measures may help inform individualised clinical assessment and management.},
}

@article {pmid42484672,
year = {2026},
author = {Shen, Z and Yu, Q},
title = {Protein arginine methyltransferases as regulators of phase separation: implications in cancer and neurodegenerative diseases.},
journal = {European biophysics journal : EBJ},
volume = {},
number = {},
pages = {},
pmid = {42484672},
issn = {1432-1017},
abstract = {Protein arginine methyltransferases (PRMTs) catalyze arginine methylation, a key post-translational modification (PTM) regulating chromatin organization, RNA metabolism, and signaling. Recent studies reveal that PRMT-mediated methylation also modulates liquid-liquid phase separation (LLPS), which organizes membraneless condensates controlling transcription, stress response, and genome stability. Dysregulated PRMT activity disrupts condensate dynamics, contributing to cancer and neurodegenerative diseases. In cancer, PRMT1, PRMT5, and PRMT6 promote tumor progression via methylation-dependent condensates that enhance oncogenic transcription and stress resistance. In the nervous system, PRMT1, PRMT4, PRMT5, PRMT6, and PRMT8 regulate LLPS of proteins, linking aberrant methylation to ALS and Huntington's disease. This review highlights PRMTs as key modulators of phase separation and potential therapeutic targets in both oncology and neurodegeneration.},
}

@article {pmid42473037,
year = {2026},
author = {Ban, Y and Wang, T and Zhang, Z and Yuan, WQ and Zhang, M and Shi, K and Li, C and Feng, Z},
title = {Tribenuron-methyl resistance in catchweed bedstraw (Galium aparine): status and MIRA-based rapid detection of ALS D376E mutation.},
journal = {Pest management science},
volume = {},
number = {},
pages = {},
doi = {10.1002/ps.71132},
pmid = {42473037},
issn = {1526-4998},
support = {2023YFD1400500//National Key Research and Development Program of China/ ; 32372567//National Natural Science Foundation of China/ ; },
abstract = {BACKGROUND: Catchweed bedstraw (Galium aparine) is a highly competitive malignant broadleaf weed that significantly reduces the yield and quality in wheat and rapeseed cropping systems. The prolonged and exclusive use of tribenuron-methyl has led to widespread resistance development, posing a significant threat to the sustainability of weed management practices. To enable timely intervention and support evidence-based decision-making, systematic monitoring of resistance status and the development of a rapid, reliable detection method are urgently required.

RESULTS: We collected 113 populations of G. aparine from major wheat-growing regions across China, among which 83 populations were found to be resistant to tribenuron-methyl. The sequencing of the ALS gene revealed six distinct mutation patterns at sites P197, D376 and W574 within resistant populations, among which D376E was the most frequently observed. To enable rapid field resistance monitoring, the multienzyme isothermal rapid amplification (MIRA) assay was developed for detecting the D376E mutation. This new detection system can assess target-site resistance within 80 min at a constant temperature of 39 °C.

CONCLUSION: This study investigated tribenuron-methyl resistance in 113 G. aparine populations from various provinces of China and generated a comprehensive resistance distribution map. The MIRA-based method for rapidly detecting the ALS D376E substitution in G. aparine was developed. Collectively, our study provides valuable knowledge and a practical tool for the management of G. aparine. © 2026 Society of Chemical Industry.},
}

@article {pmid42473039,
year = {2026},
author = {Koppisetti, RK and Barthélemy, NR and Horie, K and Ly, CV and Roberts, KF and Koutarapu, S and Perrin, RJ and Franklin, EE and Pedicone, C and Orrick, J and Melendez, J and Miller, TM and Sato, C and Ghoshal, N and Goate, AM and Karch, CM and Bateman, RJ and Mukherjee, S},
title = {Distribution of Big Tau Isoforms in the Human Central and Peripheral Nervous System.},
journal = {Annals of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ana.78300},
pmid = {42473039},
issn = {1531-8249},
support = {UL1TR004419/TR/NCATS NIH HHS/United States ; 1U54NS123746-01/NS/NINDS NIH HHS/United States ; R01NS095773/NS/NINDS NIH HHS/United States ; R01NS110890/NS/NINDS NIH HHS/United States ; U54NS123985/NS/NINDS NIH HHS/United States ; P41GM103422/GM/NIGMS NIH HHS/United States ; P01AG026276/AG/NIA NIH HHS/United States ; P01AG03991/AG/NIA NIH HHS/United States ; P30AG066444/AG/NIA NIH HHS/United States ; },
abstract = {OBJECTIVE: Tau is widely studied in neurodegeneration, yet most work has focused on canonical brain tau isoforms. A longer isoform, "big tau," produced by inclusion of exon 4a, is expressed in the peripheral nervous system (PNS) and central nervous system (CNS) regions. We sought to characterize big tau composition, anatomic distribution, and disease relevance.

METHODS: Mass spectrometry (MS) was used to sequence big tau and map its distribution across the human nervous system. Postmortem samples included brain tissue from Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and controls; spinal cord and peripheral nerves. Big and canonical ("small") tau isoforms were also quantified in cerebrospinal fluid (CSF) from controls and participants stratified by amyloid status and cognitive impairment.

RESULTS: Human big tau results from insertion of either 355 or 251 amino acids encoded by exon 4a-long and exon 4a-short, respectively. Alternative splicing of exons 2, 3, and 10 generates multiple big tau isoforms. Total tau levels were approximately 1,000-fold higher in the brain than in the PNS; however, the relative abundance of big tau increased from the CNS to the PNS, comprising 50% of the total tau in the periphery and approximately 1% in the brain, primarily localized to the cerebellum. In CSF, big tau levels were unchanged by amyloid abnormalities or cognitive impairment, whereas canonical tau increased with AD pathology.

INTERPRETATION: Big tau represents a distinct tau population enriched in the PNS and uncoupled from disease-associated changes in brain-derived tau, suggesting that distinguishing big tau from canonical tau may improve interpretation of tau biomarkers and help differentiate CNS neurodegeneration from peripheral nerve pathology. ANN NEUROL 2026.},
}

@article {pmid42473218,
year = {2026},
author = {Keskin, A and Mogulkoc, R and Baltaci, AK},
title = {Relationship Between miRNA and Neurodegenerative Diseases Such as Alzheimer's disease, Parkinson's, Huntington's disease, Amyotrophic Lateral Sclerosis.},
journal = {Mini reviews in medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0113895575484348260702044851},
pmid = {42473218},
issn = {1875-5607},
abstract = {The regulatory roles of miRNAs on CNS homeostasis, neuronal differentiation, and synaptic plasticity make these molecules indispensable for healthy brain functions. miRNA dysregulation, by triggering abnormal neurodevelopment, has a critical impact on the etiology and progression of neurodegenerative diseases. MicroRNAs (miRNAs) are short, single-stranded, non-coding ribonucleic acid (RNA) molecules, 18 to 24 nucleotides long. They play a role in posttranscriptional gene regulation by binding to complementary sequences on messenger RNA (mRNA), thereby promoting mRNA degradation or preventing translation into protein. MiRNAs are essential regulators of the genome because they bind targets and alter gene expression. MiRNA biogenesis and functions are tightly regulated, and their dysregulation is associated with various diseases, including cancer, cardiovascular diseases, and neurodegenerative disorders. In particular, disruption of the Blood-Brain Barrier in neurodegenerative diseases allows molecules to leak into the bloodstream, enabling the detection of miRNAs in other body fluids and making these fluids potential biomarker sources. In this context, miRNAs can be measured in blood, cerebrospinal fluid, and other biological samples. It has significant potential for early diagnosis, disease progression monitoring, and evaluation of treatment efficacy. In this review, the relationship between MiRNAs and neuronal degeneration diseases was evaluated. In this review, prepared in light of the current literature scanned through the PubMed database, we examined data from the last 5 years (2021-2026) on neurodegenerative diseases associated with miRNA dysregulation, including Alzheimer's Disease (AD), Parkinson's Disease (PD), Amyotrophic Lateral Sclerosis (ALS), and Huntington's Disease (HD).},
}

@article {pmid42473814,
year = {2026},
author = {Shao, D and Wen, X and Xu, X and Liu, X and Guo, B and Li, B and Wang, G and Liu, X and Men, S},
title = {Cyprosulfamide mitigates nicosulfuron phytotoxicity in maize through activation of GST-associated phase II detoxification involving ZmGST24.},
journal = {Pest management science},
volume = {},
number = {},
pages = {},
doi = {10.1002/ps.71142},
pmid = {42473814},
issn = {1526-4998},
support = {32370271//National Natural Science Foundation of China/ ; 2026KJCXZX-LYS-14//HAAFS Agriculture Science and Technology Innovation Project/ ; 254Z6303G//Project of Central Guidance for Local Science and Technology Development Funds/ ; 23JCYBJC01180//Natural Science Foundation of Tianjin/ ; 24YFXTHZ00050//Key Research and Development Program of Tianjin/ ; },
abstract = {BACKGROUND: Nicosulfuron is an acetolactate synthase (ALS)-inhibiting herbicide widely used in maize production. However, under unfavorable environmental conditions, its phytotoxicity to maize remains a practical concern. Cyprosulfamide (CSA) is an effective safener for maize, yet the contribution of glutathione S-transferases (GST)-associated phase II detoxification to CSA-conferred protection against nicosulfuron injury remains poorly understood.

RESULTS: CSA markedly alleviated nicosulfuron-induced growth inhibition in maize seedlings and effectively reduced herbicide injury under field conditions. Inhibitor assays showed that both cytochrome P450-mediated phase I metabolism and GST-associated phase II detoxification contribute to maize tolerance to nicosulfuron. Proteomic analysis further revealed that, relative to nicosulfuron treatment alone, co-application of nicosulfuron and CSA significantly enriched the glutathione metabolism pathway in maize leaves. Among the induced GST candidate genes, ZmGST24 showed the strongest transcriptional response. Phylogenetic and conserved motif analyses supported its functional similarity to previously reported GSTs involved in herbicide detoxification. Molecular docking suggested favorable binding of ZmGST24 to nicosulfuron, and heterologous expression in yeast demonstrated that ZmGST24 not only enhanced tolerance to nicosulfuron, but also increased tolerance to several herbicides commonly used in maize fields.

CONCLUSION: These findings indicate that the protective effect of CSA against nicosulfuron phytotoxicity in maize is associated with activation of GST-associated phase II detoxification. The pronounced response of the glutathione metabolism pathway, together with the functional characterization of ZmGST24, identifies this gene as a promising candidate involved in CSA-induced herbicide tolerance and as a potential target for improving herbicide safety in maize. © 2026 Society of Chemical Industry.},
}

@article {pmid42474734,
year = {2026},
author = {Zheng, Y and Bhalala, OG and Chin, KS and Watson, R and Yassi, N},
title = {Use of blood-based neurofilament light chain as an endpoint in clinical trials of neurodegenerative conditions: a scoping review.},
journal = {Journal of neurology},
volume = {273},
number = {8},
pages = {},
pmid = {42474734},
issn = {1432-1459},
mesh = {Humans ; *Neurofilament Proteins/blood ; *Neurodegenerative Diseases/blood/diagnosis ; Biomarkers/blood ; *Clinical Trials as Topic ; },
abstract = {INTRODUCTION: Neurofilament light chain (NfL) is a structural axonal protein measurable in CSF and blood, increasingly investigated as a biomarker of neuroaxonal injury in clinical and research contexts. This review aims to explore the use of blood-based NfL as an endpoint in clinical trials of neurodegenerative conditions.

METHOD: A database search of MEDLINE and EMBASE was conducted to identify interventional clinical trials and/or related post hoc analyses for neurodegenerative diseases, published between 2013 and 2024 that reported the use of serum or plasma NfL as an endpoint. Additional studies from reference lists of included trials were manually considered for inclusion where relevant. Data were charted descriptively by disease type and summarised.

RESULTS: 49 studies were included, 29 in multiple sclerosis (MS), eight in amyotrophic lateral sclerosis (ALS), six in Alzheimer's disease (AD), and six in other diseases. Across studies, reductions in NfL often paralleled improvements in primary efficacy outcomes, supporting its use as a biomarker of disease activity and treatment response. However, several studies demonstrated a lack of concordance between change in NfL and in clinical outcomes, some of which may be related to the non-disease-modifying mechanisms of the interventions studied. This necessitates careful consideration when applying blood-based NfL as a biomarker endpoint for studies involving such interventions.

CONCLUSION: Blood NfL is a promising biomarker with potential utility as a surrogate endpoint in neurological clinical trials, particularly for diseases with active axonal injury. Further validation, particularly around disease- and intervention-specific interpretation, is needed before blood NfL can be incorporated more routinely as a clinical endpoint.},
}

Humans
*Neurofilament Proteins/blood
*Neurodegenerative Diseases/blood/diagnosis
Biomarkers/blood
*Clinical Trials as Topic

@article {pmid42475136,
year = {2026},
author = {Evans, NG},
title = {Mapping the Scientific Mesolevel: Where Are We Aiming?.},
journal = {The Hastings Center report},
volume = {56},
number = {4},
pages = {48-50},
pmid = {42475136},
issn = {1552-146X},
support = {OT2OD032644/NH/NIH HHS/United States ; },
mesh = {Humans ; *Ethics, Research ; *Science/ethics/organization & administration ; },
abstract = {Susan Wolf et al.'s article "Filling the Network Gap in Research Ethics: Analyzing Ethical Issues at Scale in Big Team Science" aims to provide analysis of ethics at the level of scientific teams. But is the emphasis on formal teams the appropriate target? In this commentary, I argue that we ought to take a much broader view, looking at the "interstitial spaces" of scientific research, including the informal networks of power and esteem that shape scientific careers, the formation and function of large teams, receipt of funding, and publication. I claim that these informal networks do as much, if not more than, formal organizing efforts in structuring scientific inquiry and norms. I conclude that an ethics of team science will be richer, more rigorous, and more effective if it treats the culture of science as a central object of study and then asks which kinds of formal organizing principles best promote and protect our ethical commitments.},
}

Humans
*Ethics, Research
*Science/ethics/organization & administration

@article {pmid42475592,
year = {2026},
author = {Haim, G and Hornstein, E},
title = {The dual face of miR-146a in ALS.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {123},
number = {30},
pages = {e2617170123},
doi = {10.1073/pnas.2617170123},
pmid = {42475592},
issn = {1091-6490},
}

@article {pmid42476327,
year = {2026},
author = {Pattnaik, PP and Prusty, SK and Pati, S and Jew, KA and Bora, AK and Sahoo, J and Sahu, PK},
title = {Exploring shared genetic pathways and gene interplay in major neurodegenerative diseases: a comprehensive review.},
journal = {Gene},
volume = {1010},
number = {},
pages = {150318},
doi = {10.1016/j.gene.2026.150318},
pmid = {42476327},
issn = {1879-0038},
abstract = {Neurodegenerative diseases are progressive disorders that involve the loss and dysfunction of neurons. Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, Huntington's disease, Frontotemporal dementia are examples of diseases. While different clinically, these disorders have a common genetic, molecular and cellular basis. This review examines the common genetic pathways, along with the interactions between genes of major neurodegenerative diseases, with a focus on the key genes, such as APOE, SNCA, MAPT, TARDBP, LRRK2 and HTT. The common pathogenic mechanisms considered to play a major role in disease progression include protein misfolding and aggregation, mitochondrial dysfunction, oxidative stress, neuroinflammation, diminished autophagy, and impaired lysosomal function, as well as synaptic degeneration. The review also emphasizes the role of systems biology strategies, such as genome-wide association studies, transcriptomics, proteomics, metabolomics, interactome analysis, and multi-omics integration, to unveiling complex molecular networks in neurodegeneration. Furthermore, the emerging biomarker strategies and therapeutic strategies targeting convergence signaling pathways including NF-κB, PI3K-Akt-mTOR, MAPK and Wnt/β-catenin are summarized. The common genetic basis and the cross-connecting molecular mechanisms of the various neurodegenerative diseases could help in the discovery of new biomarkers and pan-therapeutic targets. Further advances in molecular genetics, computational biology and precision medicine are needed to enhance early detection and the creation of effective disease-modifying treatments.},
}

@article {pmid42476836,
year = {2026},
author = {Mathis, S and Le Masson, G},
title = {When algorithms speak first: The public health risk of consumer AI in ALS diagnosis.},
journal = {Journal of the neurological sciences},
volume = {},
number = {},
pages = {126098},
doi = {10.1016/j.jns.2026.126098},
pmid = {42476836},
issn = {1878-5883},
abstract = {BACKGROUND: Consumer AI platforms are increasingly used by patients to interpret medical reports, including ENMG results for ALS. While AI shows promise in controlled clinical settings (e.g., stroke imaging, melanoma detection), consumer-facing tools often provide overconfident, context-free diagnostic assertions (e.g., 'definitive evidence of ALS'), leading to premature and potentially harmful life-altering decisions.

OBJECTIVE: To highlight the clinical, ethical, and regulatory risks of unregulated AI in ALS diagnosis and propose actionable solutions.

DISCUSSION: We present a case of AI-mediated misdiagnosis, analyze the limitations of consumer-facing AI (lack of clinical context, longitudinal data, and specialist oversight), and discuss the "authority paradox" (patients trusting AI outputs over clinicians' nuanced assessments). We propose a structured 4-step clinical approach for managing AI-mediated self-diagnoses and urge regulators to classify such tools as high-risk under the EU AI Act.

CONCLUSION: The uncritical adoption of consumer AI in ALS diagnosis represents a public health risk. Clinicians, regulators, and developers must collaborate to ensure AI serves patients safely and ethically.},
}

@article {pmid42477767,
year = {2026},
author = {Zhang, H and Li, C and Yu, J and Liang, Y and Wu, Y and Cao, F},
title = {Unraveling the role of lipid metabolism in ALS risk: a Mendelian randomization analysis using GWAS data.},
journal = {Orphanet journal of rare diseases},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13023-026-04503-2},
pmid = {42477767},
issn = {1750-1172},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease. Lipid metabolism is closely related to neuronal function and energy homeostasis, but the genetic association between specific lipid species and ALS risk remains unclear.

OBJECTIVE: This study aimed to investigate the potential causal associations between genetically predicted lipid species and ALS risk using a two-sample Mendelian randomization (MR) approach.

METHODS: Summary-level GWAS data for 179 lipid species were obtained from 7,174 Finnish participants in the GeneRISK cohort. ALS GWAS data included 29,612 ALS cases and 122,656 controls. The inverse variance weighted (IVW) method was used as the primary MR approach, supplemented by MR-Egger, weighted median, weighted mode, and simple mode analyses. False discovery rate (FDR) correction was applied across all lipid traits based on IVW P values. Sensitivity analyses were conducted to assess heterogeneity, horizontal pleiotropy, and robustness.

RESULTS: After FDR correction, genetically predicted higher levels of diacylglycerol (DAG) (18:1_18:1), phosphatidylcholine (PC) (16:1_18:1), PC (18:0_18:1), phosphatidylethanolamine (PE) (O-16:1_18:2), and several triacylglycerol (TAG) species were associated with increased ALS risk. Phosphatidylinositol (PI) (16:0_18:1) showed only a nominal protective association and did not remain significant after FDR correction. Sensitivity analyses did not indicate substantial heterogeneity or horizontal pleiotropy.

CONCLUSION: This MR study provides genetic evidence supporting potential associations between specific lipid species and ALS risk. These findings highlight lipid metabolism as a relevant pathway in ALS susceptibility.},
}

@article {pmid42477825,
year = {2026},
author = {Brenner, D and Ponomarenko, A and Petrut, I and Beyrle, S and Contardo, M and Loss, I and Radke, C and Frank, J and Zimmer, E and Schlesner, M and Achenbach, P and Scheveneels, W and Aly, A and Nazlican, H and Hesebeck-Brinkmann, J and Oeckl, P and Müller, K and Siebert, R and Böckers, T and van Eijk, K and Veldink, J and Kleger, A and Mulaw, M and Andersen, PM and Forsberg, K and Weishaupt, JH and Loghmani, SB and Grehl, T and van Damme, P and Weis, J and Catanese, A},
title = {Correction: A rare missense variant impacting NEK1 kinase function is associated with ALS.},
journal = {Acta neuropathologica communications},
volume = {14},
number = {1},
pages = {},
pmid = {42477825},
issn = {2051-5960},
}

@article {pmid42479532,
year = {2026},
author = {Khan, JS and Mohammadi, M and Ammitzboll, AL and Hagen, EM and Blicher, J and Obai, I and Cardoso, ASS and Kirtas, O and Kaeseler, RL and Rasmussen, J and Struijk, LNSA},
title = {A Tendon-Driven Wrist Abduction-Adduction Joint Improves Performance of a 5 DoF Upper Limb Exoskeleton - Implementation and Experimental Evaluation.},
journal = {IEEE transactions on bio-medical engineering},
volume = {PP},
number = {},
pages = {},
doi = {10.1109/TBME.2026.3715599},
pmid = {42479532},
issn = {1558-2531},
abstract = {OBJECTIVE: Wrist function is essential in performing activities of daily living (ADLs). However, there is limited experimental evidence on the functional impact of wrist Abduction-Adduction (Ab-Ad) joint assistance in upper limb exoskeletons (ULEs) during ADLs. This study provides the first implementation and demonstration of a clock spring-based wrist Ab-Ad joint into a five degree of freedom (DoF) ULE, EXOTIC2 exoskeleton and evaluates its effect, to support individuals with severe motor impairments.

METHODS: A compact, lightweight wrist module with tendon-driven abduction and spring-driven adduction was integrated into the EXOTIC exoskeleton. Eight adults with no motor disabilities completed drinking and scratching tasks under randomized wrist-enabled and wrist-locked conditions along with a preliminary feasibility test in one individual with Amyotrophic lateral sclerosis (ALS). Kinematic and task performance metrics including wrist range of motion, task completion time, spillage and leveling metrics were assessed.

RESULTS: Implementing the wrist Ab-Ad DoF improved task success metrics. Spill incidence during the drinking task decreased from 56% to 3%, and leveling success for scratching task improved from 28% to 75%.

CONCLUSION: Integrating wrist Ab-Ad assistance improved key functional task outcomes without increasing execution time.

SIGNIFICANCE: The study provides the experimental evidence that active wrist Ab-Ad control enhances task-level performance in exoskeleton-assisted ADLs and supports the inclusion of wrist deviation in future assistive exoskeletons.},
}

@article {pmid42479906,
year = {2026},
author = {Tahedl, M and Siah, WF and Lope, J and Hengeveld, JC and Doherty, MA and McLaughlin, RL and Hardiman, O and Tan, EL and Toomey, A and Kleinerova, J and Bede, P},
title = {Neurotransmitter-Defined Degeneration Patterns in Sporadic and C9orf72-Associated Amyotrophic Lateral Sclerosis: Predilection to GABAergic, Serotonergic, Opioid, Glutamatergic, Endocannabinoid, and Microglial Systems-Implications for Therapy Development.},
journal = {Annals of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ana.78316},
pmid = {42479906},
issn = {1531-8249},
abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) has a markedly distinctive clinical and neuroradiological signature, with the preferential involvement of specific brain networks and the apparent sparing of others. The molecular underpinnings of the strikingly selective anatomical vulnerability have not been fully elucidated to date despite the potential therapeutic relevance of characterizing neurotransmitter receptor-defined susceptibility to degeneration.

METHODS: A large neuroimaging study was undertaken with 258 participants to systematically evaluate topological associations between neurodegeneration and neurotransmitter expression distributions. Patients were stratified based on their genetic profile into sporadic and C90rf72 hexanucleotide repeat expansion carriers. Anatomical associations were evaluated between patterns of atrophy and topological neurotransmitter receptor distributions. Cross-sectional and longitudinal trends were comprehensively evaluated over 4 consecutive timepoints.

RESULTS: Our analyses reveal topological associations between neurodegeneration in sporadic ALS and GABA-A receptor α5-selective component (GABAa5), serotonin 1a receptor, and kappa opioid receptor expression maps. In addition to these networks, neuronal loss in patients with GGGGCC hexanucleotide repeat expansions exhibit predilection to glutamatergic, endocannabinoid, and microglial systems. Our multi-timepoint longitudinal analyses reveal dynamic temporal associations between focal volume loss and neurotransmitter expression with increasing spatial associations with noradrenaline transporter and GABAa5, but high attrition rates preclude definite longitudinal inferences.

INTERPRETATION: Our data suggest the preferential vulnerability of GABAergic, serotonergic, kappa opioid mediated networks in sporadic ALS. In C9orf72-assocaited ALS, glutamatergic, endocannabinoid circuits are also susceptible and microglia-mediated neuroinflammation is also implicated. The comprehensive evaluation of neurotransmitter-receptor associations not only offer academic insights regarding pathophysiological processes in ALS, but may inform targeted therapy development strategies. ANN NEUROL 2026.},
}

@article {pmid42471133,
year = {2026},
author = {Rojano-Delgado, A and Sohrabi, S and Gherekhloo, J and Domínguez-Valenzuela, JA and Palma-Bautista, C and Alcántara-de la Cruz, R and De Prado, R},
title = {Evolution of multiple resistance under long-term herbicide exposure reshapes Mediterranean perennial agroecosystems.},
journal = {Environmental pollution (Barking, Essex : 1987)},
volume = {},
number = {},
pages = {128781},
doi = {10.1016/j.envpol.2026.128781},
pmid = {42471133},
issn = {1873-6424},
abstract = {Decades of intensive herbicide use in perennial cropping systems have imposed substantial environmental pressures and accelerated the evolution of herbicide-resistant weed populations. In Andalusia (southern Spain), citrus and olive orchards rely heavily on glyphosate and other herbicide modes of action, resulting in chronic ecosystem exposure, declining herbicide efficacy, and increasing chemical inputs. We surveyed ten dominant weed species across eleven orchards to characterize resistance patterns and investigate underlying physiological mechanisms relevant to environmental persistence and contaminant cycling. Rapid screening assays using six widely applied herbicides (atrazine, 2,4-D, glyphosate, oxyfluorfen, quizalofop-ethyl, and tribenuron-methyl) revealed widespread multiple and cross-resistance in both dicots and monocots. Amaranthus albus, A. viridis, Conyza bonariensis, and Solanum nigrum displayed resistance to atrazine, glyphosate, and tribenuron-methyl, while Lolium rigidum and Sorghum halepense showed broad-spectrum resistance involving target-site alterations and enhanced metabolic detoxification, partially reversed by the cytochrome P450 inhibitor malathion. Complementary biochemical assays targeting PSII, ALS, ACCase, and EPSPS, together with diagnostic tests for PPO- and auxin-related herbicides, indicated diverse non-target-site resistance pathways, suggesting increased herbicide transformation and altered degradation dynamics in soil-plant systems. The emergence of complex resistance mechanisms reflects prolonged selection pressure from intensive herbicide regimes and implies elevated risks of environmental accumulation, off-target effects, and reduced sustainability of chemical-based weed control. These findings highlight the need to reduce herbicide dependence and adopt integrated weed management strategies that minimize pollutant loads in Mediterranean agroecosystems.},
}

@article {pmid42471678,
year = {2026},
author = {Ekowa, JL and Onyekwelu, AI and Fatai, KE},
title = {Physiotherapy and rehabilitation for survivors of female genital mutilation/cutting: a scoping review.},
journal = {BMC women's health},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12905-026-04708-4},
pmid = {42471678},
issn = {1472-6874},
abstract = {BACKGROUND: Female genital mutilation/cutting (FGM/C) affects more than 230 million girls and women worldwide and is associated with chronic pelvic pain, pelvic floor dysfunction, lower urinary tract symptoms, psychosexual dysfunction, and reduced quality of life. Although physiotherapy and rehabilitation may contribute to multidisciplinary care, the available evidence has not been comprehensively synthesised.

OBJECTIVE: To map the existing evidence on physiotherapy and rehabilitation for women living with FGM/C and identify evidence gaps relevant to clinical practice and future research.

METHODS: A scoping review was conducted following the Arksey and O'Malley framework, Levac et al.'s methodological enhancements, and PRISMA-ScR guidelines. Electronic databases and grey literature were searched from inception to January 2026. Eligible studies included adolescent (≥ 15 years) and adult women living with FGM/C, together with rehabilitation-relevant studies involving healthcare professionals. Data were charted and synthesised narratively.

RESULTS: Of 872 records identified, 21 studies met the inclusion criteria. Most evidence was observational or descriptive, with only one randomized controlled trial and one rehabilitation-focused case report directly evaluating rehabilitation interventions. Frequently reported rehabilitation-related impairments included psychosexual dysfunction, chronic pelvic pain, pelvic floor dysfunction, lower urinary tract symptoms, dyspareunia, and reduced quality of life. Reported rehabilitation approaches included pelvic floor rehabilitation, bladder retraining, biofeedback, psychosexual rehabilitation, and multidisciplinary care. Only one study included adolescents, and none specifically evaluated rehabilitation interventions for this population.

CONCLUSION: Women living with FGM/C experience substantial rehabilitation needs affecting physical, psychosexual, urinary, and psychosocial health. Although physiotherapy and rehabilitation are increasingly recognised as important components of multidisciplinary care, direct evidence evaluating rehabilitation interventions remains limited. Future research should prioritise rehabilitation-focused intervention studies, implementation research, and standardised outcome measures to strengthen the evidence base and inform comprehensive, survivor-centred care.},
}

@article {pmid42471754,
year = {2026},
author = {Xia, CA and Salarian, M and Gartshore, CJ and Scaglione, A and Hayes, T and Liu, S and Tsai, HM and Echavarren, J and Cid, JM and Matzeu, A and Szardenings, AK},
title = {Development and characterization of a novel TDP-43 positron emission tomography tracer: [[18]F]JNJ-TDP43-1.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {7},
pages = {e71675},
pmid = {42471754},
issn = {1552-5279},
support = {//Johnson & Johnson/ ; },
mesh = {Animals ; *Positron-Emission Tomography/methods ; *DNA-Binding Proteins/metabolism ; *Brain/diagnostic imaging/metabolism ; Rats ; Mice ; Humans ; Male ; Disease Models, Animal ; TDP-43 Proteinopathies/diagnostic imaging ; *Radiopharmaceuticals/pharmacokinetics ; Fluorine Radioisotopes ; },
abstract = {INTRODUCTION: Neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), limbic-predominant age-related TDP-43 encephalopathy (LATE), and Alzheimer's disease (AD) are associated with TAR DNA-binding protein 43 (TDP-43) pathology. A positron emission tomography (PET) tracer targeting TDP-43 aggregates could improve early diagnosis and guide treatment development for TDP-43-related conditions.

METHODS: Specific binding was evaluated using fluorescent labeling of compound, surface plasmon resonance (SPR), and autoradiography (ARG). Brain PET imaging in rats, nonhuman primate (NHP), and a disease mouse model was performed to characterize tracer pharmacokinetics and in vivo target binding.

RESULTS: JNJ-TDP43-1 exhibited high binding affinity for pathological TDP-43 (Kd = 7.1 nM) and remarkable selectivity over other proteinopathies. PET imaging demonstrated robust brain uptake and rapid washout in rodents and NHP. In vivo target engagement was confirmed in an AAV-hTDP43 disease model.

DISCUSSION: [[18]F]JNJ-TDP43-1 is a promising PET ligand for early diagnosis and evaluating therapies in TDP-43-related diseases.},
}

Animals
*Positron-Emission Tomography/methods
*DNA-Binding Proteins/metabolism
*Brain/diagnostic imaging/metabolism
Rats
Mice
Humans
Male
Disease Models, Animal
TDP-43 Proteinopathies/diagnostic imaging
*Radiopharmaceuticals/pharmacokinetics
Fluorine Radioisotopes

@article {pmid42472717,
year = {2026},
author = {Fowler, C and Kaelber, DC and Bliwise, DL and Greer, MK},
title = {Rapid Eye Movement Sleep Suppressing Antidepressant Prescription is Associated with Improved Survival in Amyotrophic Lateral Sclerosis.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {8},
pages = {},
pmid = {42472717},
issn = {1590-3478},
support = {UM1TR004528//Clinical and Translational Science Collaborative of Cleveland, School of Medicine, Case Western Reserve University/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/mortality/drug therapy ; Female ; Male ; *Antidepressive Agents/therapeutic use/pharmacology ; *Riluzole/therapeutic use ; Middle Aged ; *Sleep, REM/drug effects ; Aged ; },
abstract = {INTRODUCTION: Rapid eye movement (REM) sleep is a period of physiological vulnerability for patients with neuromuscular disease, owing to a generalized loss of muscle tone that spares only the diaphragm. Several antidepressants have been observed to reduce REM sleep fraction on polysomnography. We investigated whether prescription of REM-suppressing antidepressants (RSAs) versus non-REM-suppressing antidepressants (NRSAs) is associated with differential survival in patients with amyotrophic lateral sclerosis (ALS).

METHODS: Using the U.S. Collaborative Network of the TriNetX Analytics platform, we compared 1-year mortality in ALS patients prescribed RSAs or NRSAs within 3 months of diagnosis, identified by ICD-10-CM-coded encounter diagnoses with riluzole prescription between May 2014 and May 2024. We used Cox proportional hazards models, Kaplan-Meier analysis, and risk difference analysis, with and without propensity score matching (PSM).

RESULTS: Among 14,441 patients with ALS and riluzole prescription, 5,057 were prescribed either RSAs (N = 4,177) or NRSAs (N = 880). The NRSA cohort had a higher risk of death (HR 1.28, 95% CI 1.11 - 1.46), with 1-year survival of 60.73% versus 68.61% for RSAs (log-rank p<0.001). After PSM, the difference narrowed and was borderline by log-rank test (60.97% vs 65.92%, p=0.035), while the risk-difference analysis was no longer significant (RR 1.07, 95% CI 0.92 - 1.25), indicating an attenuated and statistically fragile association.

CONCLUSIONS: RSA prescription was associated with modestly better survival, but this association weakened markedly after matching and cannot establish causation; residual confounding, particularly by indication, cannot be excluded. These findings are hypothesis-generating, and prospective studies incorporating polysomnography and ALS-specific prognostic factors are needed.},
}

Humans
*Amyotrophic Lateral Sclerosis/mortality/drug therapy
Female
Male
*Antidepressive Agents/therapeutic use/pharmacology
*Riluzole/therapeutic use
Middle Aged
*Sleep, REM/drug effects
Aged

@article {pmid42468019,
year = {2026},
author = {Gou, CY and Smith, SE},
title = {Interventional Procedures for Musculoskeletal Pain in ALS Patients: A Case Series.},
journal = {American journal of physical medicine & rehabilitation},
volume = {105},
number = {8},
pages = {e117-e120},
doi = {10.1097/PHM.0000000000002964},
pmid = {42468019},
issn = {1537-7385},
mesh = {Humans ; Male ; Middle Aged ; *Amyotrophic Lateral Sclerosis/complications ; Female ; *Musculoskeletal Pain/etiology/therapy/drug therapy ; Retrospective Studies ; *Pain Management/methods ; Aged ; Adult ; },
abstract = {Many patients with amyotrophic lateral sclerosis (ALS) experience musculoskeletal pain, yet data on the safety and efficacy of interventional procedures for pain relief in this population are limited. This study aims to describe the characteristics, outcomes, and procedural considerations of pain interventions performed for musculoskeletal pain in ALS patients. A retrospective chart review was conducted of ALS patients referred for interventional pain management by a neuromuscular physiatrist at a single academic institution's interdisciplinary ALS Center between February 2021 and February 2025. Eleven patients (mean age: 57 y, 64% male) underwent 14 procedures. Shoulder pain was the most common indication (43%), followed by spine (29%) and hip (14%) pain. Procedures mostly consisted of joint and bursal injections peripherally and of epidural injections in the axial spine. Overall, 13 of 14 (93%) procedures provided at least "good" pain relief, and 5 patients elected to repeat their procedures. One patient experienced transient postprocedure hypertension; no major complications occurred. Interventional procedures, particularly corticosteroid injections, appear to be safe and effective for managing focal musculoskeletal pain in patients with ALS. Tailored procedural techniques and multidisciplinary coordination can enhance comfort and optimize outcomes in this complex population.},
}

Humans
Male
Middle Aged
*Amyotrophic Lateral Sclerosis/complications
Female
*Musculoskeletal Pain/etiology/therapy/drug therapy
Retrospective Studies
*Pain Management/methods
Aged
Adult

@article {pmid42468211,
year = {2026},
author = {Seo, Y and Lee, J and Lee, Y and Kim, S and Lee, JS and Ro, H and Cho, SH and Park, JS and Kim, MJ and Park, HC},
title = {FUS-driven zebrafish model of ALS identifies tribenzylamine as a candidate modulator of ALS-associated pathology.},
journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie},
volume = {202},
number = {},
pages = {119761},
doi = {10.1016/j.biopha.2026.119761},
pmid = {42468211},
issn = {1950-6007},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by motor neuron loss and declining motor function; however, effective therapies remain limited. To support unbiased therapeutic discovery, we aimed to develop a high-throughput phenotypic screening platform based on a transgenic zebrafish model expressing the human ALS-associated FUS-R521C mutant (mtFUS). This model was generated using a modified QF-based binary expression system and exhibited early-onset pathological features, including elevated oxidative stress, progressive neuronal degeneration, and impaired locomotor activity, thereby recapitulating the key aspects of FUS-associated ALS. Transcriptomic profiling revealed molecular signatures resembling those reported in patient-derived motor neurons, including dysregulated neuroactive ligand-receptor signaling, immune activation, and stress-response pathway alterations. Using this platform, we identified tribenzylamine (TBA) as a candidate compound that improves locomotor performance and significantly reduces reactive oxygen species levels. Integrated transcriptomic and biochemical analyses suggested that TBA induces coordinated molecular changes, including normalization of neuronal activity-related gene expression, modulation of immune and metabolic pathways, and restoration of hormone-related signaling. TBA reversed FUS-induced reductions in key neuronally active sex steroids, including estrogen and progesterone, and increased estrogen-responsive gene expression, suggesting a partial recovery of neuronally active sex steroid homeostasis. These findings support the mtFUS zebrafish model as a useful platform for ALS drug discovery and identify TBA as a candidate modulator of ALS-associated phenotypes, with effects linked to transcriptomic remodeling and neuronally active sex steroid signaling.},
}

@article {pmid42468901,
year = {2026},
author = {Halabian, N and Park, C and Omoto, L and Bocca, LF and Palacios, G and Wu, K and Hamani, C and Rabin, J and Abrahao, A and Davidson, B and Lipsman, N and Meng, Y},
title = {Focused ultrasound blood brain barrier opening for targeted therapeutics in neurodegenerative diseases.},
journal = {Biological psychiatry},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.biopsych.2026.07.008},
pmid = {42468901},
issn = {1873-2402},
abstract = {Therapeutic focused ultrasound (FUS) leverages the non-invasive ultrasonic waves to modify the biological tissue. When administered alongside intravenous microbubbles, low-intensity FUS enables transient, targeted disruption of the blood-brain barrier (BBB), permitting passage of systemically administered therapeutics into the central nervous system (CNS) with high spatial precision. The ability to selectively modulate BBB permeability at the disease site has the potential to substantially expand the number of therapeutics that can be utilized in treating illnesses afflicting the CNS. Herein, we review the current applications of FUS for treating neurodegenerative disorders and diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic lateral sclerosis (ALS). We discuss the research developments to date and future directions.},
}

@article {pmid42469515,
year = {2026},
author = {Kreß, L and Abuzant, M and Zeller, D and Sommer, C},
title = {Beyond ALS: split-hand syndrome in immune-mediated motor neuropathies.},
journal = {Journal of neurology},
volume = {273},
number = {8},
pages = {},
pmid = {42469515},
issn = {1432-1459},
support = {Z-2/CSP_22//Interdisziplinäres Zentrum für Klinische Forschung, Universitätsklinikum Würzburg/ ; Z-3 BC-18//Interdisziplinäres Zentrum für Klinische Forschung, Universitätsklinikum Würzburg/ ; Z-2/AdvCSP-4//Interdisziplinäres Zentrum für Klinische Forschung, Universitätsklinikum Würzburg/ ; },
mesh = {Humans ; Female ; Male ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnosis ; Middle Aged ; Aged ; *Muscle, Skeletal/physiopathology ; Prospective Studies ; *Hand/physiopathology ; Adult ; Nerve Conduction Studies ; Diagnosis, Differential ; },
abstract = {BACKGROUND AND AIMS: Split-hand syndrome describes selective wasting and weakness of the abductor pollicis brevis (APB) or first dorsal interosseous (FDI) muscles with relative preservation of the abductor digiti minimi (ADM). Beyond clinical definition, two neurophysiological ratios and one index have been proposed to quantify this pattern. It is considered a potential diagnostic criterion for amyotrophic lateral sclerosis (ALS). Its occurrence in immune-mediated neuropathies, as differential diagnoses, remains unclear. We aimed to investigate clinical and electrophysiological manifestations of split-hand syndrome in multifocal motor neuropathy (MMN) and multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) compared to ALS.

METHODS: We prospectively examined 26 MMN, 16 MADSAM, and 22 ALS patients. All underwent neurological examination and neurophysiological measurements of compound muscle action potentials (CMAP) from the APB, FDI, and ADM bilaterally after median (APB) and ulnar nerve (FDI, ADM) stimulation. Split-hand ratios (APB/ADM; FDI/ADM) and split-hand index (SI) were calculated.

RESULTS: Clinical split-hand syndrome was present in 16/26 (62%) MMN, 7/16 (44%) MADSAM, and 12/22 (54%) ALS patients. Electrophysiological criteria (abnormal split-hand ratios or SI; ≥ 1 parameter fulfilled) were similarly frequent across groups (MMN 17/26, 65%, MADSAM 11/16, 69%, and ALS 16/22, 73%). CMAP ratios and SI did not differ between groups in the overall analysis and showed no correlation with disease duration or severity. Diagnostic models showed limited discriminatory power (area under the curve ≤ 0.61).

INTERPRETATION: Split-hand syndrome occurs in MMN, MADSAM, and ALS at comparable frequencies and lacks robust or consistent diagnostic discrimination across disease groups.},
}

Humans
Female
Male
*Amyotrophic Lateral Sclerosis/physiopathology/diagnosis
Middle Aged
Aged
*Muscle, Skeletal/physiopathology
Prospective Studies
*Hand/physiopathology
Adult
Nerve Conduction Studies
Diagnosis, Differential

@article {pmid42469634,
year = {2026},
author = {Li, MA and Song, YZ and Li, T and Wu, J and Tao, Y and Hu, R and Qiao, CM and Cui, C and Zhao, WJ and Shen, YQ},
title = {Secretory leukocyte protease inhibitor (SLPI) attenuates TLR4/NF-κB-mediated neuroinflammation in amyotrophic lateral sclerosis: a candidate molecule associated with neuro-pathology.},
journal = {Molecular medicine (Cambridge, Mass.)},
volume = {},
number = {},
pages = {},
doi = {10.1186/s10020-026-01572-8},
pmid = {42469634},
issn = {1528-3658},
support = {KYCX25_2743//Postgraduate Research & Practice Innovation Program of Jiangsu Province/ ; 82171429//National Natural Science Foundation of China/ ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disorder driven by neuroinflammation involving activated microglia and astrocytes, which accelerates the loss of motor neurons. While Secretory leukocyte protease inhibitor (SLPI) is known for its immunomodulatory properties, its specific role in ALS pathogenesis has not been fully established. This study aimed to characterize the expression patterns and functional significance of SLPI in ALS models.

METHODS: The study utilized SOD1[G93A] mice to analyze the spatiotemporal dynamics of SLPI expression in the gastrocnemius muscle, lumbar spinal cord, and serum across different disease stages. In vitro functional assays were conducted using siRNA-mediated knockdown of SLPI in BV2 (microglia), MA (astrocytes), and NSC-34 (motor neurons) cell lines. Additionally, recombinant SLPI protein was applied to LPS-stimulated BV2 cells to investigate its effect on the TLR4/ NF-κB signaling pathway.

RESULTS: In SOD1[G93A] mice, SLPI was significantly upregulated in the gastrocnemius muscle from the pre-symptomatic stage (60 days) through the late stage (130 days). In the lumbar spinal cord, SLPI showed a transient initial increase but declined sharply by the end-stage; a similar significant reduction was observed in late-stage serum levels. In vitro, SLPI knockdown exacerbated pro-inflammatory cytokine production in all three cell types and impaired the antioxidant capacity of NSC-34 motor neurons. Mechanistically, recombinant SLPI attenuated inflammation in BV2 cells by modulating the TLR4/NF-κB pathway.

CONCLUSIONS: The dynamic changes in SLPI levels suggest its potential relevance as a candidate molecule for disease staging. Meanwhile, its protective effects in regulating inflammation suggest that it could be a promising therapeutic candidate for mitigating ALS-associated neuroinflammation.},
}

@article {pmid42470084,
year = {2026},
author = {Morgado Linares, RY and Rojas-Marcos, Í and Mesa, M and Martínez, E and Cabrera-Serrano, M and Paradas, C},
title = {Impact of Sexuality in Patients With Motor Neuron Disease.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70348},
pmid = {42470084},
issn = {1097-4598},
abstract = {INTRODUCTION: Sexuality is a relevant yet understudied aspect in people living with motor neuron disease (MND). This study aimed to assess whether sexuality in people with MND is influenced by motor, cognitive, behavioral, or mood disturbances, and to explore whether being sexually active impacts caregiver burden.

METHODS: We conducted a cross-sectional observational study involving participants with MND and their primary caregivers from three ALS multidisciplinary units in Seville, Spain. Data were collected between October 2018 and July 2021. Functional, cognitive, behavioral, and mood assessments were conducted. Sexuality was evaluated through sex-specific questionnaires. Caregiver burden was assessed using the Zarit Burden Interview.

RESULTS: Among 66 participants who completed the sexuality assessment, 42.9% reported sexual activity in the previous month. Of these, 70% had no sexual dysfunction, while 26.7% had moderate and 3.3% severe dysfunction. No correlation was found between sexual activity and motor function. Sexual activity was less frequent in participants with apathy (p = 0.026), depression (p = 0.021), and frontotemporal dementia (p = 0.013). Among sexually active patients, those with cognitive impairment-particularly memory dysfunction-had higher rates of orgasm difficulties (p = 0.019). No other clinical parameters were related to sexuality. Sexuality of participants with MND did not influence caregiver burden.

DISCUSSION: Sexuality in MND is more associated with cognitive and mood factors than with motor disability. Addressing sexuality in clinical practice may contribute to improving quality of life and should be integrated into the multidisciplinary care of MND patients.},
}

@article {pmid42471032,
year = {2026},
author = {Barrera-Chamorro, L and Gonzalez-de la Rosa, T and Arzalluz-Luque, J and Torrecillas-Lopez, M and Marquez-Paradas, E and Claro-Cala, CM and Navarro-Hortal, MD and Eichau, S and Garcia-Sanchez, MI and Montserrat-de la Paz, S},
title = {Sustainable next-generation prebiotics for brain health: microbiota-gut-brain axis in neurodegenerative and demyelinating diseases.},
journal = {Critical reviews in food science and nutrition},
volume = {},
number = {},
pages = {1-22},
doi = {10.1080/10408398.2026.2703335},
pmid = {42471032},
issn = {1549-7852},
abstract = {Neurodegenerative and neuroinflammatory diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis, are increasingly associated with disruption of the microbiota-gut-brain axis. Common alterations include reduced beneficial microbial taxa, impaired short-chain fatty acid production, intestinal and blood-brain barrier dysfunction, and sustained inflammatory responses. These findings support the development of microbiota-targeted dietary interventions. This review summarizes current evidence on polyphenols, bioactive peptides, and pectin-derived oligosaccharides (POS) as prebiotic or prebiotic-like compounds with potential activity through the microbiota-gut-brain axis. Particular attention is given to structure-function relationships, host-microbe interactions, and the sustainable recovery of these compounds from food by-products. Preclinical studies suggest that these bioactives may reduce microglial activation, improve mitochondrial function, strengthen intestinal and blood-brain barrier integrity, and enhance cognitive or motor performance. Early clinical studies also indicate possible benefits on mood, selected cognitive outcomes, metabolic regulation, and inflammatory biomarkers, although evidence remains limited. Microbiota-derived metabolites from polyphenols, such as urolithins, together with glycomacropeptide and POS, appear to be key mediators. However, clinical validation in major neurodegenerative diseases remains fragmented. Standardized formulations, mechanistic trials, harmonized endpoints, and precision-nutrition strategies are required to confirm their therapeutic potential.},
}

@article {pmid42466609,
year = {2026},
author = {Li, D and Zhou, Z and Liang, G and Zeng, D and Zhou, Z and Li, X and Qiu, T and Zhang, Y and Lin, J and Chen, Y and Li, Z},
title = {Association Between Allostatic Load, Genetic Susceptibility, and Liver Cancer Incidence: A Large-Scale Prospective Cohort Study.},
journal = {International journal of cancer},
volume = {},
number = {},
pages = {},
doi = {10.1002/ijc.70583},
pmid = {42466609},
issn = {1097-0215},
support = {240421166496919//Shantou Medical Science and Technology Planning Project/ ; A2023481//Medical Scientific Research Foundation of Guangdong Province, China/ ; B2025664//Medical Scientific Research Foundation of Guangdong Province, China/ ; //Shantou University Medical College 2025 Teaching Reform Project/ ; },
abstract = {Allostatic load (AL) reflects the cumulative physiological burden of chronic stress throughout life, potentially influencing cancer onset and prognosis. However, its association with primary liver cancer (PLC) risk and potential interaction with genetic susceptibility remains unclear. To investigate this, we analyzed 374,632 UK Biobank participants. AL was evaluated using a composite score of 13 cardiovascular, metabolic, and immune biomarkers, while a weighted polygenic risk score (PRS) categorized genetic susceptibility. Multivariable Cox proportional hazards models and restricted cubic splines were utilized to estimate hazard ratios (HRs) and evaluate dose-response relationships. Over a median 12.4-year follow-up, a significant dose-response correlation between AL and PLC risk was observed. In the fully adjusted model, a 1-unit increase in AL was associated with a 17% increased risk (HR = 1.17, 95% CI: 1.12-1.23), and participants in the highest AL quartile exhibited a 2.60-times higher risk than those in the lowest (HR = 2.60, 95% CI: 1.72-3.95). Despite no multiplicative interaction, stratified analyses revealed AL's impact was most substantial in individuals with intermediate genetic risk (HR = 2.00, 95% CI: 1.38-2.90), who constitute the population majority. Additionally, the risk was heightened in overweight/obese individuals and more pronounced among non-smokers. Ultimately, cumulative physiological stress, indicated by AL, is strongly associated with PLC, supporting the "wear-and-tear" theory of its development. This research highlights a "malleable zone" in individuals with moderate genetic risk, suggesting that lowering AL may meaningfully aid in preventing PLC.},
}

@article {pmid42467162,
year = {2026},
author = {Barker-Jones, B and Navvuga, P and Baji, P and Marques, E and Hollingworth, W},
title = {Comparing User-Written Codes for Performing Economic Evaluations in Stata.},
journal = {PharmacoEconomics},
volume = {},
number = {},
pages = {},
pmid = {42467162},
issn = {1179-2027},
support = {RP-PG-0610-10048//National Institute for Health and Care Research/ ; PB-PG-0213-30021//National Institute for Health and Care Research/ ; },
abstract = {BACKGROUND: Several user-written Stata codes exist for trial-based economic evaluations, but they lack assessment and guidance. This study aimed to identify and compare publicly available user-written Stata codes for trial-based economic evaluations.

METHODS: A focused literature search of Ovid Medline, SSC Archive, The Stata Journal and Google Scholar was conducted to identify relevant codes to June 2025. Codes were applied to data from two clinical trials, both featuring missing data and covariate adjustment. Codes were compared in terms of their ability to estimate key economic parameters and produce graphical outputs and functionality in handling four common statistical challenges: correlated costs and effects, covariate adjustment, skewed costs and effects, and missing data.

RESULTS: We identified eight codes reported in four publications: codes for assessing health economic agreement (Gallacher et al.), sampling uncertainty for cost-effectiveness analysis (Glick et al.) and codes addressing missing data (Mutubuki et al. and Faria et al.). Gallacher et al.'s codes reported lower incremental quality-adjusted life years (QALYs) and net monetary benefit than Glick's et al.'s codes. Mutubuki et al. and Faria et al.'s codes produced comparable incremental costs and QALYs, though Faria et al. yielded wider confidence intervals in cost estimates.

DISCUSSION: Differences in estimates across statistical approaches show that code choice can influence economic evaluation results. Some codes were better suited for generating basic economic outputs, whereas others provide more comprehensive analyses or address specific statistical challenges including missing data. However, no single code provided all key outputs while addressing the main statistical challenges.},
}

@article {pmid42467293,
year = {2026},
author = {Hassan, MA and Al Amin, M and Sweilam, SH and Abohassan, M and Krishnan, K and Gupta, JK and Jahnavi, P and Vodeti, R and Radha, R and Gupta, PS and Reddy, KTK},
title = {Resveratrol and neuroprotection: modulation of cellular dynamics and signaling networks in neurodegenerative diseases.},
journal = {Inflammopharmacology},
volume = {},
number = {},
pages = {},
pmid = {42467293},
issn = {1568-5608},
abstract = {Progressive loss of neurons, oxidative stress, neuroinflammation, and mitochondrial dysfunction are hallmarks of neurodegenerative diseases (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Resveratrol, a polyphenolic phytoalexin mainly found in grapes and red wine, is a promising treatment candidate due to its diverse biological effects and neuroprotective properties. This review demonstrates the regulatory effects of resveratrol on cellular signaling pathways linked to NDs and its neuroprotective mechanisms. Resveratrol enhances neuronal survival, boosts mitochondrial biogenesis, and mitigates oxidative stress by affecting key molecular pathways, including SIRT1/AMPK, PI3K/Akt, MAPK, and Nrf2/ARE. The PI3K/Akt and ERK1/2 pathways promote neuronal regeneration by modulating pro-apoptotic and anti-apoptotic factors. Resveratrol inhibits NF-κB, reducing cytokine release and microglial activation, thereby exhibiting anti-inflammatory properties. It improves cognitive function, synaptic plasticity, and neuronal survival. Despite an increasing pharmacological profile, its practical applicability is limited by inadequate bioavailability, rapid metabolism, and restricted brain penetration. This review demonstrates resveratrol's effect on interconnected signaling networks related to neurodegeneration. We critically compare evidence from preclinical and clinical studies, demonstrating both therapeutic potential and translational limitations. Emerging nanotechnology-based delivery strategies are demonstrated to overcome bioavailability and blood-brain barrier penetration challenges. These insights provide a translational perspective for the future development of resveratrol-based interventions in NDs.},
}

@article {pmid42467750,
year = {2026},
author = {Deressa, JD and Behaksra, SW and Molla, E and Letebo, A and Shumie, G and Adnew, B and Alemayehu, DH and Kassa, FA and Seyoum, T and Tafa, EB and Woldekidan, K and Ejigu, LA and Huwe, T and Keffale, M and Bayissa, GA and Koepfli, C and Chala, B and Asmamaw, Y and Tadesse, FG and Gadisa, E},
title = {Therapeutic efficacy of artemether-lumefantrine plus single low dose primaquine for the treatment of uncomplicated Plasmodium falciparum malaria in a high transmission setting, Western Ethiopia.},
journal = {PloS one},
volume = {21},
number = {7},
pages = {e0335833},
pmid = {42467750},
issn = {1932-6203},
mesh = {Humans ; *Primaquine/therapeutic use/administration & dosage ; *Artemether, Lumefantrine Drug Combination/therapeutic use/administration & dosage ; *Malaria, Falciparum/drug therapy/transmission/epidemiology/parasitology ; *Antimalarials/therapeutic use/administration & dosage ; Female ; Male ; Ethiopia/epidemiology ; Plasmodium falciparum/drug effects/genetics ; Child, Preschool ; Adolescent ; Treatment Outcome ; Child ; Adult ; Drug Therapy, Combination ; Young Adult ; },
abstract = {BACKGROUND: The development and spread of drug-resistant parasites continue to threaten progress toward malaria elimination. Therapeutic efficacy and molecular resistance marker studies are needed to guide national control programs. In African settings, evidence of partial resistance to artemisinin-based combination therapies (ACTs) associated with Pfkelch13 mutations is accumulating, and World Health Organization (WHO) recommends regular monitoring of first line antimalarial drugs for early detection of resistant parasites. In this study, we evaluated the efficacy of artemether-lumefantrine (AL) combined with a single low dose of primaquine (PQ) for treating uncomplicated Plasmodium falciparum malaria in a co-endemic area where P. falciparum predominates.

METHODS AND FINDINGS: One hundred twenty-three patients with P. falciparum mono-infection were enrolled between November 2020 to March 2021 and treated with artemether-lumefantrine (AL) plus a single low dose of primaquine (PQ) as per the national malaria treatment guideline and followed up for 28 days. Ethical approval was obtained from the AHRI/ALERT ethics committee (Po/23/19), and the study was registered at Pan-African clinical trials registry (PACTR) with unique identification number of PACTR202509595696440. Pfmsp2 capillary electrophoresis (CE) genotyping was used to differentiate recrudescence from new infections. More than half (56.1%) of the participants had high parasitemia (>10,000 parasites/μL) at enrollment. On day 3, 16.9% (20/118) remained parasitemic, and of the 10 individuals with detectable gametocytes at enrollment, only 3.4% remained gametocytemic on day 3, and 100% parasite clearance was observed on day 7, respectively. Multiplicity of infection was 3.8 at enrollment and 1.7 at the time of recurrence. The adequate clinical and parasitological responses at 28-day (ACPR) of per protocol analysis (PPA) was 73.7% for PCR-uncorrected and 91.3% for PCR-corrected, respectively and while, the intention-to-treat analysis (ITA), the Kaplan-Meier estimated treatment success at day 28 was 93.2% (95% CI: 88.5-98.2) after PCR correction, compared with 78.3% (95% CI: 71.0-86.4) in the PCR-uncorrected analysis. In our study assessment, no cases of severe malaria or serious adverse events occurred.

CONCLUSIONS: The efficacy observed in this study, although remaining above the WHO policy change threshold after PCR correction, may indicate a potential decline in AL's effectiveness in this high transmission setting. However, because antimalarial drug concentrations were not measured and evening doses were not fully directly observed, reduced drug exposure or imperfect adherence cannot be excluded as possible contributors to the observed treatment outcomes Therefore, we suggest regular therapeutic efficacy monitoring and further investigation using advanced molecular techniques, such as next-generation sequencing (NGS), to enable early detection of resistance-associated parasite variants that may compromise treatment efficacy.},
}

Humans
*Primaquine/therapeutic use/administration & dosage
*Artemether, Lumefantrine Drug Combination/therapeutic use/administration & dosage
*Malaria, Falciparum/drug therapy/transmission/epidemiology/parasitology
*Antimalarials/therapeutic use/administration & dosage
Female
Male
Ethiopia/epidemiology
Plasmodium falciparum/drug effects/genetics
Child, Preschool
Adolescent
Treatment Outcome
Child
Adult
Drug Therapy, Combination
Young Adult

@article {pmid40364629,
year = {2026},
author = {Sepehrimanesh, M and Xu, W and Ding, B},
title = {Comparative analysis of chemical and lentiviral approaches in the generation of human induced pluripotent stem cell-derived motor neurons.},
journal = {Neural regeneration research},
volume = {21},
number = {7},
pages = {2968-2974},
pmid = {40364629},
issn = {1673-5374},
support = {R56 NS133252/NS/NINDS NIH HHS/United States ; },
abstract = {The generation of human induced pluripotent stem cell–derived motor neurons overcomes limited access to human tissues and offers an unprecedented approach to modeling motor neuron diseases such as dystonia and amyotrophic lateral sclerosis. Motor neurons generated through different strategies may exhibit substantial differences in purity, maturation, characterization, and even neuronal identity, leading to variable outcomes in disease modeling and drug screening. However, very few comparative studies have been conducted to determine the similarities and differences among motor neurons prepared via different protocols. In this study, we prepared human induced pluripotent stem cell–derived motor neurons via lentiviral delivery of transcription factors and chemical induction and performed a systematic comparative analysis. We found that motor neurons generated by both approaches showed typical motor neuron morphology and robustly expressed motor neuron-specific markers, such as nuclear homeobox transcription factor 9 and choline acetyltransferase. The chemical induction protocol utilizes a combination of small molecules to induce motor neuron differentiation, offering a significantly faster maturation time of 35 days compared to 46 days with lentiviral delivery of transcription factors. Additionally, while lentiviral delivery of transcription factors are suitable for downstream biochemical analysis, chemical induction are more applicable for therapeutic approaches as they avoid the use of lentiviruses. Both approaches produce motor neurons with high purity (> 95%) and yield. No significant differences were found between chemical induction and lentiviral delivery of transcription factors in terms of motor neuron markers and maturation markers. These robust methodologies offer researchers powerful tools for investigating motor neuron diseases and potential therapeutic strategies.},
}

@article {pmid42464213,
year = {2026},
author = {Özbilici, Z and Issı, ES},
title = {SYNE1-Related motor neuron disease-like phenotype with mild distal contractures and 24-month clinical stability: a case report.},
journal = {BMC neurology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12883-026-05142-7},
pmid = {42464213},
issn = {1471-2377},
abstract = {BACKGROUND: SYNE1 encodes nesprin-1, a nuclear envelope protein involved in cytoskeletal linkage, nuclear positioning, and neuromuscular integrity. Biallelic SYNE1 variants cause a broad spectrum ranging from cerebellar ataxia to arthrogryposis multiplex congenita and motor neuron disease-like phenotypes. Distinguishing these entities can be difficult when subtle distal contractures coexist with neurogenic electrophysiological findings.

CASE PRESENTATION: A 22-year-old woman born to consanguineous parents presented with bilateral intrinsic hand muscle wasting, impaired fine motor performance, and mild gait difficulty. Examination showed distal hand atrophy, mild weakness of the abductor pollicis brevis and first dorsal interosseous muscles, brisk deep tendon reflexes, preserved sensation, and mild distal finger contractures. Sensory nerve conduction studies were normal. Motor studies showed reduced compound muscle action potential amplitude in the right abductor pollicis brevis and borderline-low amplitude on the left. Needle electromyography showed widespread chronic neurogenic motor unit changes affecting the upper and lower extremities, with active denervation most evident in the bilateral abductor pollicis brevis muscles. Genioglossus examination was normal. SMN1 deletion testing and selected familial amyotrophic lateral sclerosis gene testing were negative. Whole exome sequencing identified a homozygous truncating SYNE1 variant, NM_182961.4:c.21009G > A; p.(Trp7003Ter). Segregation analysis confirmed heterozygous carrier status in both parents and two unaffected siblings. At 24-month follow-up, weakness, atrophy, contractures, reflex pattern, and functional status remained clinically stable, without bulbar, cerebellar, sensory, or clinically evident respiratory involvement.

CONCLUSIONS: This case supports classification as a SYNE1-related motor neuron disease-like phenotype with mild distal contractures rather than an isolated arthrogryposis multiplex congenita type 3 (AMC3) phenotype. The case also supports including SYNE1 in genetic testing panels for young patients with unexplained motor neuron disease-like presentations, particularly when consanguinity, normal sensory conduction, and subtle distal contractures coexist.},
}

@article {pmid42464712,
year = {2026},
author = {Gao, N and Cui, B and Yun, Y and Yu, W and Gao, X and Sun, X and Shao, K and Lin, P and Liu, F and Li, W and Zhao, Y and Yu, D and Yan, C and Liu, S and Lou, J},
title = {Corticospinal Subfiber Neurite Density Index Detects Upper Motor Neuron Degeneration in Prediagnostic Patients With Sporadic Amyotrophic Lateral Sclerosis.},
journal = {European journal of neurology},
volume = {33},
number = {7},
pages = {e70703},
pmid = {42464712},
issn = {1468-1331},
support = {82471429//National Natural Science Foundation of China/ ; ZR2024MH013//Natural Science Foundation of Shandong Province/ ; 2025CXPT133//the Key Research and Development Program of Shandong Province, China/ ; Z-2017-24-2509//the Yantu Neuroscience Specialized Research Fund Project/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology/diagnostic imaging/blood/diagnosis ; Female ; Male ; *Pyramidal Tracts/diagnostic imaging/pathology ; Middle Aged ; *Neurites/pathology ; Retrospective Studies ; Aged ; Neurofilament Proteins/blood ; Diffusion Magnetic Resonance Imaging ; Diffusion Tensor Imaging ; *Motor Neurons/pathology ; *Nerve Degeneration/pathology/diagnostic imaging ; },
abstract = {BACKGROUND: Using multi-shell diffusion MRI, we aimed to identify whether corticospinal tract (CST) subfiber damage can be detected in prediagnostic amyotrophic lateral sclerosis (ALS) patients. We also explored whether the combination of serum neurofilament light chain (NfL) levels and CST subfiber abnormalities may provide better diagnostic performance in differentiating prediagnostic ALS patients from disease controls (DCs) and healthy controls (HCs) than single markers.

METHODS: In this retrospective study, prediagnostic ALS was used as an operational term for patients who presented at baseline with chronic progressive limb weakness or bulbar symptoms, had no clinically evident typical UMN signs, and were subsequently confirmed to have sporadic ALS according to the Awaji criteria during longitudinal follow-up. Patients whose final diagnosis was not ALS after follow-up were classified as disease controls. Probabilistic tractography was performed on baseline MRI data to assess CST subfiber damage in 47 ALS patients, 20 DCs, and 51 HCs.

RESULTS: Compared with Controls, ALS patients had significantly lower neurite density index (NDI) values of CST subfibers, particularly those originating from the primary and supplementary motor cortex. The diagnostic performance of the combined model incorporating serum NfL and CST subfiber NDI values in differentiating prediagnostic ALS patients from HCs and DCs was 0.925 and 0.928, respectively, which was better than that of single markers (0.634-0.886 and 0.699-0.856, respectively).

CONCLUSIONS: Our findings suggest that CST subfibers NDI values are promising neuroimaging markers for detecting in vivo UMN degeneration in prediagnostic ALS. Moreover, combining blood and neuroimaging markers may further improve early diagnostic performance.},
}

Humans
*Amyotrophic Lateral Sclerosis/pathology/diagnostic imaging/blood/diagnosis
Female
Male
*Pyramidal Tracts/diagnostic imaging/pathology
Middle Aged
*Neurites/pathology
Retrospective Studies
Aged
Neurofilament Proteins/blood
Diffusion Magnetic Resonance Imaging
Diffusion Tensor Imaging
*Motor Neurons/pathology
*Nerve Degeneration/pathology/diagnostic imaging

@article {pmid42465739,
year = {2026},
author = {You, Y and Zhu, H and Zhang, Q and Wang, J and Dong, C and Yang, Z and Zhang, J and Zhang, Y and Zhang, M and Lu, M and Du, C},
title = {Development and efficacy of ex vivo expanded autologous regulatory T cells for the treatment of amyotrophic lateral sclerosis.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1854252},
pmid = {42465739},
issn = {1664-3224},
mesh = {*Amyotrophic Lateral Sclerosis/therapy/immunology/genetics ; *T-Lymphocytes, Regulatory/immunology/transplantation/metabolism ; Animals ; Humans ; Mice ; Disease Models, Animal ; Female ; Superoxide Dismutase-1/genetics ; Mice, Transgenic ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with limited therapeutic options, in which neuroinflammation critically drives disease progression. Regulatory T cells (Tregs) exert potent immunosuppressive and neuroprotective effects, offering great potential for ALS treatment. However, clinical application of Treg therapy is hampered by low peripheral cell abundance and unstable expansion quality. Here, we established and optimized a GMP-grade protocol for sorting and expanding peripheral blood-derived Tregs, and validated cryopreserved apheresis products as feasikble starting materials. Although ALS patient-derived Tregs showed reduced expansion capacity compared with healthy donor counterparts, they maintained comparable purity, stable regulatory phenotypes, and robust immunosuppressive function. Transcriptomic analysis confirmed the lineage fidelity and low pro-inflammatory characteristics of expanded Tregs. Therapeutic efficacy was verified in SOD1G93A ALS and GvHD mouse models with delayed disease progression and relieved inflammation. This study provides standardized GMP manufacturing strategies and solid preclinical evidence to support the ongoing clinical trial (NCT06671236) and facilitate Treg immunotherapy translation for ALS.},
}

*Amyotrophic Lateral Sclerosis/therapy/immunology/genetics
*T-Lymphocytes, Regulatory/immunology/transplantation/metabolism
Animals
Humans
Mice
Disease Models, Animal
Female
Superoxide Dismutase-1/genetics
Mice, Transgenic

@article {pmid42466415,
year = {2026},
author = {Mei, A and Jewett, D and Jewett, A and Kaur, K and Malarkannan, S},
title = {Multi-hit genetic lesions and a stress-imprinted immune transcriptome define the inflammatory pathology in ALS patients.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {42466415},
issn = {2693-5015},
abstract = {Amyotrophic lateral sclerosis (ALS) is a genetically heterogeneous neurodegenerative disease whose peripheral immune architecture remains incompletely defined. Here, we integrated whole-genome sequencing and single-cell RNA sequencing to define genomic and immune correlates of ALS. Genome-wide analysis of a monozygotic twin pair discordant for ALS pathology identified shared ALS-associated variants, as well as patient-enriched variants in genes linked to RNA metabolism, neurodegeneration, and immune inflammation, supporting a multilayered genetic architecture. Single-cell profiling of 40,484 peripheral blood mononuclear cells from three ALS patients and two healthy individuals, including 33,667 cells retained after quality control, resolved 13 immune clusters and revealed broad remodeling of the peripheral immune compartment, with relative enrichment of natural killer, mucosal-associated invariant T, and γδ T-cell populations. Across immune subsets, ALS samples exhibited inflammatory and stress-adapted transcriptomic programs, including TNF-α/NF-κB, IFN-γ, hypoxia, and ribosomal stress pathways. These data support a model in which multi-hit genetic susceptibility converges on a stress-induced immune transcriptome, marked uniquely by innate lymphocyte activation in ALS patients.},
}

@article {pmid42459525,
year = {2026},
author = {Majumdar, S and Samaiya, PK and Ahmed, S and Prajapati, SK},
title = {Imaging biomarkers in neurodegenerative diseases: advances and challenges.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1813588},
pmid = {42459525},
issn = {1663-4365},
abstract = {Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS), represent a major global health burden. Imaging biomarkers have emerged as important tools for improving the diagnosis, monitoring, and biological characterization of neurodegenerative diseases. Structural MRI, diffusion tensor imaging (DTI), functional MRI (fMRI), positron emission tomography (PET), hybrid PET/MRI and molecular imaging have transformed our ability to investigate neurodegeneration in vivo non-invasively. This review highlights updated information on how each imaging modality offers a unique window into different disease pathophysiology including regional atrophy, amyloid-β, tau, dopaminergic terminal degeneration, synaptic density (SV2A), and neuroinflammation. We also focused on the translational and evidence supporting biomarkers, appropriate use criteria for amyloid and tau PET imaging, and standardized quantification methods such as the Centiloid scale. The growing role of multimodal fusion, where imaging is increasingly integrated with scalable fluid biomarkers to enable "blood-first" strategies where high-risk patients are selectively referred to advanced imaging, improving feasibility and equity. Despite tremendous progress, there are still issues with their standardization, sensitivity, specificity, and clinical translation. Moreover, the review emphasizes the frontiers of α-synuclein and glial state-specific PET ligands, advanced diffusion models, and dynamic connectivity analysis to support precision medicine and mechanism-based trial design for NDDs.},
}

@article {pmid42459857,
year = {2026},
author = {Hu, M and You, L and Zhang, X and Xuan, Z and Ma, S and Wu, X},
title = {Experimental evidence of electroacupuncture in ALS mouse models: a systematic review and meta-analysis.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1780176},
pmid = {42459857},
issn = {1664-2295},
abstract = {OBJECTIVE: This study aimed to systematically evaluate the therapeutic efficacy of electroacupuncture (EA) in amyotrophic lateral sclerosis (ALS) and to elucidate the underlying neurobiological mechanisms by synthesizing preclinical evidence.

METHODS: According to the PICOS principle, relevant studies were searched in the following databases: PubMed, Web of Science, Embase, Cochrane Library, Scopus, and CNKI. Search terms and strategies were determined based on MeSH terms. The methodological quality of the included studies was assessed using the SYRCLE's Risk of Bias tool and the CAMARADES checklist. Meta-analysis was performed using Stata 15.0 and Rstudio software.

RESULTS: Seventeen studies involving 372 animals were included. The quality scores of the included studies ranged from 5 to 8, with an average score of 7. The meta-analysis of the primary outcome, the rotarod test score, showed a significant improvement in the EA group compared to the control group [SMD = 3.31, 95% CI (2.05, 4.57), Z = 5.151, p < 0.001], indicating that EA can enhance motor function in ALS mice. Regarding secondary outcomes, EA intervention alleviated neuroinflammation, promoted neuronal survival, improved axonal regeneration inhibition, and stabilized RNA metabolism homeostasis. Consequently, it slowed disease progression, improved motor performance, prolonged survival time, and effectively protected motor neurons at the histopathological level (p < 0.05). These findings underscore the potential of EA as a promising multimodal therapeutic strategy for ALS. For the heterogeneity observed in the rotarod test, sensitivity analysis, subgroup analysis, and meta-regression did not identify its source. However, potential publication bias was detected, which might contribute to the heterogeneity. The heterogeneity for other outcome measures might originate from differences in stimulation parameters (e.g., waveform), acupoint selection, or treatment duration.

CONCLUSION: This meta-analysis demonstrates that EA confers significant neuroprotective benefits in preclinical ALS models, primarily through multi-target modulation of key pathological processes such as neuroinflammation, aberrant cell death signaling, and RNA metabolism. These preclinical findings underscore the potential of electroacupuncture as a complementary neuroprotective strategy and warrant further investigation in rigorous clinical trials.

https://www.crd.york.ac.uk/PROSPERO/view/CRD420251229183.},
}

@article {pmid42459893,
year = {2026},
author = {Ogino, M},
title = {Single-subject auditory ERP-BCI performance enhancement in ALS via an AI coding assistant prompt.},
journal = {Frontiers in human neuroscience},
volume = {20},
number = {},
pages = {1869918},
pmid = {42459893},
issn = {1662-5161},
abstract = {INTRODUCTION: Auditory event-related potential (ERP) brain-computer interfaces (BCIs) offer communication support for individuals with amyotrophic lateral sclerosis (ALS) who eventually progress to completely locked-in states. However, individual-specific BCI pipeline optimization is technically demanding and time-consuming, leaving substantial room for performance improvement in practice. A central challenge is increasing selection speed while maintaining reliable classification accuracy, since slower selections reduce the sense of agency and undermine the motivational and feedback dynamics essential for sustained BCI use.

METHODS: We investigated whether an AI coding assistant could address this challenge for individual patients. A three-class auditory ERP-BCI was optimized for a single ALS patient using Claude Code (Anthropic, Inc.), which iteratively generated and evaluated 23 optimization scripts over approximately 24 hours with minimal human-in-the-loop oversight. The resulting AI-Designed ERP classifier (AIDE) was evaluated on 189 EEG trials spanning 3.5 years using five cross-validation strategies.

RESULTS: For the baseline models, halving the stimulus repetitions to shorten selection time degraded classification accuracy; AIDE prevented this degradation, achieving 85.03% mean cross-validation accuracy (selection time 17 s; ITR 2.92 bits/min). This doubled the information transfer rate from 1.43 to 2.92 bits/min. Accuracy exceeded 84% across four of five cross-validation strategies. Feature space visualization revealed that the AI autonomously selected and combined EEG features established in prior studies into an effective discriminative architecture, without domain-specific algorithmic guidance from the human researcher. In addition, online test confirmed 66.7% accuracy for AIDE versus 50.0% for the baseline model.

DISCUSSION: These findings provide proof of concept that single-subject BCI performance can be improved via a single prompt, offering an efficient pathway to individualized optimization in clinical and research settings.},
}

@article {pmid42460499,
year = {2026},
author = {Leichsenring, F and Heim, N and Steinert, C},
title = {Conceptual problems and questionable evidence in defining non-inferiority margins - a reply to Flückiger et al.},
journal = {Psychotherapy research : journal of the Society for Psychotherapy Research},
volume = {},
number = {},
pages = {1-3},
doi = {10.1080/10503307.2026.2701025},
pmid = {42460499},
issn = {1468-4381},
abstract = {From 19 meta-analyses comparing active bona fide treatments, Flückiger et al. (2026) recently calculated a between-group effect size (SMD) of -0.17 for primary outcomes and of -0.16 for secondary outcomes. They suggested using these effect sizes as empirically derived non-inferiority margins. However, Flückiger et al.'s approach is conceptually problematic and lacks empirical support. Without a rationale, empirically found differences between active treatments cannot per se be regarded as non-inferiority margins.},
}

@article {pmid42460524,
year = {2026},
author = {Cai, X and Bai, Y and Ma, F and Xu, R and Xie, Y and Cao, X},
title = {Mechanisms and Therapeutic Targeting of the cGAS-STING Pathway in Central Nervous System Disorders.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X472988260627201746},
pmid = {42460524},
issn = {1875-6190},
abstract = {OBJECTIVE: The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway is a core DNA-sensing axis in innate immunity and has been increasingly implicated in the pathogenesis of multiple Central Nervous System (CNS) disorders. This review summarizes current knowledge of cGAS-STING signaling in CNS disorders and evaluates its therapeutic potential.

METHODS: Relevant studies on cGAS-STING signaling in CNS disorders were collected from PubMed and Web of Science, with emphasis on disease mechanisms, neuroinflammatory regulation, and pathway-targeted therapeutic strategies.

RESULTS: In the CNS, cGAS-STING signaling exhibits marked region-, cell-, and pathology-dependent heterogeneity. Aberrant DNA sensing activates this pathway and amplifies neuroinflammation, cellular stress, and tissue injury in Alzheimer's Disease (AD), Parkinson's Disease (PD), Amyotrophic Lateral Sclerosis (ALS), ataxia-telangiectasia (A-T), and ischemic and hemorrhagic stroke. Pharmacological inhibition of cGAS, cyclic GMP-AMP (cGAMP), or STING, together with emerging delivery strategies, has shown promise in preclinical models.

DISCUSSION: Clinical translation remains limited by incomplete validation of pathway specificity, limited human evidence, restricted brain delivery, and inconsistent efficacy assessment.

CONCLUSION: The cGAS-STING pathway links aberrant DNA sensing to innate immune activation and CNS pathology. Clarifying its disease-, cell-, and stage-specific roles may support future targeted therapeutic strategies for CNS disorders.},
}

@article {pmid42460525,
year = {2026},
author = {Liu, Y and Yang, J and Su, J and Hao, L},
title = {High Levels of Plasma Neurturin Partially Mediate the Protective Effect of Reduced Ruminococcus2 Abundance on Multiple Sclerosis: A Mendelian Randomization Study.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X468669260626223524},
pmid = {42460525},
issn = {1875-6190},
abstract = {BACKGROUND: Genetic evidence implicates the contribution of the gut-brain axis to neurodegenerative diseases (NDDs). Alterations in gut microbiota and inflammation are key pathophysiological contributors. Elucidating the genetic basis and the role of cytokines can provide insights into mechanisms linking gut microbial composition to neurodegeneration.

METHODS: Using aggregated statistics from five large-scale Genome-Wide Association Studies (GWAS) on Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, multiple sclerosis, and amyotrophic lateral sclerosis, bidirectional two-sample Mendelian Randomization (MR) was used to examine the associations. A two-step multivariable Mendelian randomization approach incorporates data from 91 cytokines to explore potential mediators.

RESULTS: The study reveals 18 positive and 17 negative effects between gut microbiota and NDDs, as well as 10 positive and 10 negative effects between cytokines and NDDs. Remarkably, mediation analysis identified a causal pathway, with evidence that plasma neurturin levels partially mediate the association from genus Ruminococcus2 to multiple sclerosis, with a mediation proportion of 19.19% (OR = 1.038, 95% CI = 1.001-1.086, P = 0.044). No pleiotropy or heterogeneity was detected.

DISCUSSION: These MR findings provide compelling evidence for a genetically anchored gutimmune-brain network in NDDs, with cytokines as intermediates. Bidirectional effects highlight disease-specific microbial signatures and inflammatory contexts. The Ruminococcus2-neurturin pathway in multiple sclerosis may offer mechanistic specificity, aligning with neurotrophic and anti-inflammatory signaling pathways.

CONCLUSION: This study emphasizes the importance of gut microbiota alterations in NDDs and explores inflammation's partial intermediary role. The findings suggest potential targets for personalized neurodegeneration prevention strategies.},
}

@article {pmid42460529,
year = {2026},
author = {Chen, H and Yang, Z and Meng, H and Hu, Z and Ke, Z and Ye, Q and Xu, Y and Wu, J and Liu, Z},
title = {White Matter Functional Dysregulation in Amyotrophic Lateral Sclerosis: Machine Learning-Based Biomarkers and Transcriptomic Signatures.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X465668260629073047},
pmid = {42460529},
issn = {1875-6190},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by motor system degeneration, yet its white matter (WM) functional pathophysiology remains underexplored.

METHODS: This study utilized resting-state functional magnetic resonance imaging to decode WM functional abnormalities in 50 ALS patients and 55 healthy controls. Next, machine learning analysis was applied to evaluate the utility of these WM functional patterns in diagnosing ALS and predicting disease progression, and their pathophysiological mechanisms were preliminary explored through neurotransmitter mapping and imaging transcriptomics.

RESULTS: ALS patients exhibited reduced activity in central WM regions (including bilateral corticospinal tracts), accompanied by elevated activity in anterior and posterior WM territories. The aberrant topological properties and disrupted functional connectivity are predominantly localized within bilateral precentral/postcentral WM networks. A support vector machine model incorporating these features achieved 75.24% classification accuracy and predicted the rate of disease progression (r = 0.56, p = 0.001). The spatial pattern of WM dysfunction in ALS was associated with both the spatial distribution of disease-related neurotransmitters and the expression profiles of specific genes.

DISCUSSION: Our findings reveal distinct WM functional dysfunction patterns in ALS and their molecular-genetic underpinnings, providing novel insights into the pathophysiological mechanisms of ALS.

CONCLUSION: ALS involves specific patterns of WM dysfunction, and these WM-centric biomarkers may facilitate the development of therapeutic monitoring frameworks for this devastating disease.},
}

@article {pmid42461162,
year = {2026},
author = {Zhang, R and Zhang, N and Li, B and Liu, Q and Xu, C and Li, B and Zhang, J},
title = {Nursing a Patient With Amyotrophic Lateral Sclerosis Stage 4B With Epilepsy: A Case Study.},
journal = {Nursing in critical care},
volume = {31},
number = {4},
pages = {e70573},
pmid = {42461162},
issn = {1478-5153},
support = {25ZZJJLW-015//Medical Research Council Foundation of the 305 Hospital of the PLA/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/nursing/complications ; *Epilepsy/nursing/complications ; Male ; Intensive Care Units ; *Critical Care Nursing/methods ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a rare motor neuron disease characterised by progressive muscle weakness, which can eventually lead to death. So far there is no effective cure for it. This case report discusses the nursing of a patient with stage 4B amyotrophic lateral sclerosis complicated with epilepsy and sudden disturbance of consciousness during his stay in an intensive care unit (ICU). After 34 days of treatment and care, the patient regained consciousness with stable vital signs before being transferred out of the ICU. This report focusses on nursing interventions adopted in terms of respiratory management, nutritional management, psychological care and exercise during both the epileptic seizure and the awake period of the patient in the hope of providing a reference for the nursing of patients with amyotrophic lateral sclerosis with epilepsy in intensive care units.},
}

Humans
*Amyotrophic Lateral Sclerosis/nursing/complications
*Epilepsy/nursing/complications
Male
Intensive Care Units
*Critical Care Nursing/methods

@article {pmid42461445,
year = {2026},
author = {Mitsumoto, H and Cheung, K and Matsumoto, T and Lanza, I and Oskarsson, B and Johnson, S and Petterson, XT and Jang, GE and Andrews, HF},
title = {Metabolomic analyses of amyotrophic lateral sclerosis, muscle cramps, and TJ-68 treatment.},
journal = {Metabolomics : Official journal of the Metabolomic Society},
volume = {22},
number = {4},
pages = {},
pmid = {42461445},
issn = {1573-3890},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/metabolism/drug therapy/blood ; *Muscle Cramp/drug therapy/metabolism/blood ; *Metabolomics/methods ; Female ; Male ; Middle Aged ; Aged ; Cross-Over Studies ; Medicine, Kampo ; *Drugs, Chinese Herbal/therapeutic use ; },
abstract = {INTRODUCTION: Most patients with amyotrophic lateral sclerosis (ALS), a fatal motor neuron disease, experience painful muscle cramps. Our recent pilot trial of the Japanese Kampo medicine TJ-68 suggested its efficacy in improving muscle cramps in patients with ALS.

OBJECTIVES: This study analyzed plasma metabolomic changes to identify the underlying mechanisms of muscle cramps in ALS and the effects of TJ-68.

METHODS: Plasma was obtained from 11 participants with ALS in the repeated crossover trial at five time points (baseline, two placebo phases, and two TJ-68 phases). Metabolites were analyzed using mass spectrometry. Linear mixed-effects models were applied to identify metabolite changes associated with muscle cramps, determine the effects of TJ-68 on metabolites, and predict which participants would respond to TJ-68.

RESULTS: Higher glutamine/glutamate, arginine, and leucine levels were associated with more severe muscle cramps. TJ-68 treatment increased tryptophan and aconitate levels but reduced serotonin and acetylcarnitine levels. Long-chain acylcarnitine levels were correlated with muscle cramp severity, and their levels tended to decrease with treatment. Uric acid, β-aminoisobutyric acid, α-aminoadipic acid, and acetylcholine emerged as predictors of the efficacy of TJ-68.

CONCLUSION: This study identified the metabolite profile of muscle cramps in ALS and the changes in metabolite levels after TJ-68 treatment. Several baseline metabolites were associated with the prediction of the response to muscle cramps following TJ-68 treatment. Uric acid might be particularly useful because of its easy measurement in standard assays. Our study affirms the value of metabolomic technology for future pharmacotherapy and studies in ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/metabolism/drug therapy/blood
*Muscle Cramp/drug therapy/metabolism/blood
*Metabolomics/methods
Female
Male
Middle Aged
Aged
Cross-Over Studies
Medicine, Kampo
*Drugs, Chinese Herbal/therapeutic use