@article {pmid41793180,
year = {2026},
author = {Smith, SE and Miller, TM and Atkinson, A and Pestronk, A and Bucelli, RC},
title = {Integrating Serum Neurofilament Light Chain Into Amyotrophic Lateral Sclerosis Diagnostic Criteria.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70212},
pmid = {41793180},
issn = {1097-4598},
abstract = {INTRODUCTION/AIMS: Serum neurofilament light chain (NfL) is a promising diagnostic biomarker for differentiating amyotrophic lateral sclerosis (ALS) from clinical mimics. This study assessed the utility of integrating serum NfL into current diagnostic criteria to enhance diagnostic certainty in patients with a provisional ALS diagnosis who were confirmed as having ALS at follow-up.

METHODS: We conducted a single-center, retrospective study of consecutive patients with a provisional ALS diagnosis at their initial visit at the WashU Medicine ALS Center. All underwent electrodiagnostic testing and serum NfL measurement via SIMOA using an HD-X analyzer (Quanterix). Elevated serum NfL was defined with a cutoff of 38 pg/mL.

RESULTS: The study included 43 patients with a provisional ALS diagnosis (29 men [67.4%]; median age, 63 years [range, 36-80 years]). At follow-up, 27/43 (62.8%) patients progressed to definite ALS. Serum NfL was elevated in 34/43 (79.1%) of the total cohort and 24/27 (88.9%) of those who progressed to definite ALS. Integrating serum NfL with Gold Coast Criteria (GCC) was associated with a tenfold increase in the odds of identifying patients likely to progress to definite ALS (OR 10 [1.39, 71.87], p = 0.02).

DISCUSSION: Our results suggest that serum NfL is a robust complement to current ALS diagnostic criteria and shows potential to improve early identification and diagnostic certainty of patients likely to progress to definite ALS. Integrating serum NfL with GCC provided the strongest predictive model. These findings warrant larger multicenter, prospective studies to confirm results.},
}

@article {pmid41792996,
year = {2026},
author = {Magen, I and Kaneb, HM and Masnata, M and Pulimood, N and Emde, A and Genge, A and Hornstein, E},
title = {Cell free miRNAs are pharmacodynamic biomarkers for enhanced Dicer activity by Enoxacin in human patients with Amyotrophic lateral sclerosis.},
journal = {Molecular therapy : the journal of the American Society of Gene Therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ymthe.2026.03.002},
pmid = {41792996},
issn = {1525-0024},
abstract = {The activity of the RNase III enzyme DICER is downregulated in both sporadic and genetic forms of Amyotrophic Lateral Sclerosis (ALS). Accordingly, hundreds of microRNAs (miRNAs) are broadly downregulated, leading to de-repression of their mRNA targets. Enoxacin is a fluoroquinolone that enhances DICER activity and miRNA biogenesis. Here, we tested for the first time the molecular effect of Enoxacin on miRNA biogenesis in ALS patients and demonstrated that Enoxacin's engagement with DICER can be pharmacodynamically monitored via miRNA levels in human subjects. In an investigator-initiated, first-in-human study (REALS1), we explored miRNAs as pharmacodynamic biomarkers of DICER activation. Patients with sporadic ALS received oral Enoxacin twice daily for 30 days in a double-blind, randomized clinical trial. The study demonstrated comparable Enoxacin levels in plasma and cerebrospinal fluid (CSF). Furthermore, an increase in cell-free miRNA levels in both plasma and CSF at all time points following Enoxacin treatment (400 mg or 800 mg/day), was measured relative to baseline. Additionally, no serious adverse events were reported. In conclusion, pharmacological enhancement of DICER activity by Enoxacin increases miRNA biogenesis in patients with ALS. These results support further investigation of Enoxacin efficacy in larger clinical trials.},
}

@article {pmid41792976,
year = {2026},
author = {Shah, JS and Oskarsson, B and Zhou, X and Heckman, MG and Sledge, HJ and Virador, G and Parizadeh, D and Middlebrooks, EH},
title = {Expanding the Motor Band Sign in Motor Neuron Disease Using 7T MRI: Visualization of Cortical Layer-Dependent Iron Deposition in the Primary Motor Cortex.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70179},
pmid = {41792976},
issn = {1097-4598},
abstract = {INTRODUCTION/AIMS: There are no established biomarkers of upper motor neuron degeneration to aid in the diagnosis of motor neuron disease (MND). This study examines the diagnostic value of the motor band sign as a marker of upper motor neuron degeneration and its relationship to clinical findings in MND.

METHODS: Records of consecutive patients who underwent 7T magnetic resonance imaging (MRI) between October 2021 and April 2025 for evaluation of MND or other neurologic indications were retrospectively reviewed. Clinical variables and plasma neurofilament light chain (pNfL) levels were recorded. An upper motor neuron score (Mayo UMNS) was derived from reflex scores. Blinded MRI review assessed the degree of susceptibility-weighted imaging (SWI) hypointensity in the hand, foot, and bulbar motor cortex regions.

RESULTS: An MBS was observed in 100 of 117 (85.5%) MND patients and in 16 (15.5%) patients with non-MND diagnoses, corresponding to a sensitivity of 85.5% (78.0%-90.7%) and 84.5% (76.2%-90.2%) specificity. The MBS in 78 MND patients (70.9%) preferentially involved the middle and deep cortical layers, giving a trilaminar appearance, while only one non-MND patient had this finding. Mayo UMNS (β = 0.89, p < 0.001), pNfL (β = 0.63, p = 0.033), and age at evaluation (β = 0.68, p = 0.027) were independently associated with the summed SWI score.

DISCUSSION: The 7T MRI MBS is a sensitive and specific marker for MND that complements established clinical evaluation. Using 7T, a trilaminar appearance of the motor cortex, reflecting known histopathological changes, can be visualized and may be specific to MND.},
}

@article {pmid41792723,
year = {2026},
author = {Huang, NX and Cai, ZW and Zhuang, SP and Lin, HY and Chen, S and Zou, ZY and Wu, Y and Chen, HJ},
title = {Impairment of brain short association fibers across clinical stages in amyotrophic lateral sclerosis: a new biomarker mirroring disease progression.},
journal = {BMC medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12916-026-04770-7},
pmid = {41792723},
issn = {1741-7015},
support = {2024J01625//Natural Science Foundation of Fujian Province/ ; 2024Y9256//Fujian Province Joint Funds for the Innovation of Science and Technology/ ; 2024Y9253//Fujian Province Joint Funds for the Innovation of Science and Technology/ ; 82572160//National Natural Science Foundation of China/ ; 2023CXA009//Fujian Provincial Health Technology Project/ ; },
abstract = {BACKGROUND: A quantitative biomarker for clinical staging is essential for amyotrophic lateral sclerosis (ALS) stratification. This study evaluated microstructural impairment in brain short association fibers (SAFs) across ALS stages via neurite orientation dispersion and density imaging (NODDI) and assessed correlations with disease severity.

METHODS: Diffusion-weighted imaging data were collected from 87 ALS patients (categorized into four groups King's stages) and 37 healthy controls. Whole-brain SAF mapping was performed via a spherical deconvolution-driven probabilistic tractography approach. Diffusion tensor imaging (DTI) and NODDI parameters (neurite density index, NDI; orientation dispersion index, ODI; isotropic volume fraction, ISO) were estimated for each SAF.

RESULTS: Seven SAFs connecting the left postcentral-precentral gyrus, left precentral-precentral gyrus, right postcentral-precentral gyrus, right paracentral-posterior cingulate gyrus, left paracentral-posterior cingulate gyrus, left precentral-superior parietal gyrus, and left precentral-superior frontal gyrus exhibited significant NDI differences across the five groups. Additionally, one fiber connecting the left medial orbitofrontal-rostral anterior cingulate gyrus demonstrated an ISO difference [false discovery rate (FDR)-corrected p < 0.05]. Progressive trends of NDI reduction and ISO increase were observed at higher ALS stages. No intergroup differences were found in the ODI or DTI parameters. The NDI values of these seven SAFs were positively correlated with disease severity scores (FDR-corrected p < 0.05). Combining NDI and ISO revealed moderate classification potential for ALS (area under the curve = 0.780).

CONCLUSIONS: Neurite injury in SAFs involving primary motor and extramotor areas worsened alongside clinical staging and motor disability in ALS. NODDI provides quantitative SAF-related biomarkers for assessing ALS disease severity.},
}

@article {pmid41792545,
year = {2026},
author = {Færge, S and Muldtofte, L and Ustrup, M and Mikkelsen, AKK and Speyer, H},
title = {Recognizing epistemic injustice in healthcare: a case for methodological pluralism.},
journal = {Medicine, health care, and philosophy},
volume = {},
number = {},
pages = {},
pmid = {41792545},
issn = {1572-8633},
abstract = {Nielsen et al. (2025) recently presented a critique of the current scholarship on epistemic injustice in healthcare, emphasizing the absence of robust empirical evidence, the conceptual difficulty of establishing criteria for identification, and the risk of theoretical misapplication of Miranda Fricker's original framework. While the call for nuance and careful theoretical articulation might be worthwhile, the framing of their critique risks reinforcing precisely the patterns of epistemic exclusion that the concept of epistemic injustice is meant to expose. The implication that epistemic injustice must be operationalized and empirically validated in large-scale quantitative studies before it can be acknowledged as clinically and ethically significant may inadvertently replicate a longstanding hierarchy of knowledge in which certain forms of suffering become "real" only once translated into quantifiable data. In this response, we aim to advance the scholarly debate by questioning the argumentative basis of Nielsen et al.'s claim that fundamental scientific, conceptual, and theoretical flaws undermine the field of epistemic injustice in healthcare. We propose instead approaching epistemic injustice with social objectivity and methodological pluralism; the concept should not be dismissed for lacking quantification or standardization, but rather recognized for its complexity and significance in improving equity, care, and clinical encounters.},
}

@article {pmid41791963,
year = {2026},
author = {Mendon, A and Jain, S and Mishra, N and Bagwe Parab, S},
title = {Calprotectin as an immune-dysregulation biomarker in amyotrophic lateral sclerosis: Insights for diagnosis and therapy.},
journal = {Revue neurologique},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neurol.2026.02.148},
pmid = {41791963},
issn = {0035-3787},
abstract = {Motor neuron degeneration is a defining feature of amyotrophic lateral sclerosis (ALS), a progressive and fatal neurodegenerative disorder. Early diagnosis remains challenging due to the absence of reliable and validated biomarkers. Calprotectin, a well-established inflammatory marker in various neuroinflammatory conditions, has paradoxically been found at reduced levels in the blood of ALS patients in a limited number of studies, raising the hypothesis of immune dysregulation rather than classical neuroinflammation. However, these findings are primarily derived from small patient cohorts and have yet to be independently replicated. This review critically assesses the emerging role of calprotectin in ALS by comparing it with other candidate biomarkers, including vascular endothelial growth factor (VEGF), apolipoprotein A1 (ApoA1), interleukin-8 (IL-8), interleukin-7 (IL-7), and interleukin-10 (IL-10). While calprotectin may reflect a distinct immunological profile, its standalone diagnostic value remains unclear. Nonetheless, its integration into a multi-analyte biomarker panel could enhance diagnostic precision and biological insight. The review also explores underlying immunological mechanisms, including receptor interactions (RAGE, TLR4, CD33), cellular mediators (microglia, lymphocytes, monocytes), and therapeutic implications. Future research should prioritize mechanistic investigation of calprotectin modulation in ALS, longitudinal validation in larger cohorts, and integration within multimodal biomarker frameworks. A better understanding of disease-specific immune alterations may contribute to earlier diagnosis, stratified patient monitoring, and targeted therapeutic development.},
}

@article {pmid41791528,
year = {2026},
author = {Tolkachjov, SN},
title = {Response to Li et al.'s "Comment on 'Gene Expression Profiling (GEP) in Dermatology, Part 2: Clinical Applications'-toward safe, patient-centered implementation.".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2026.02.108},
pmid = {41791528},
issn = {1097-6787},
}

@article {pmid41791354,
year = {2026},
author = {Gan, Y and Ju, R and Peng, Y and Xiao, S and Qiu, R and Wang, S and Zhang, Y and Guo, L and Gu, W},
title = {A multi-platform analytical strategy for Atractylodes lancea authentication: Fusion of stable isotope, elemental, chromatographic, and spectroscopic profiles.},
journal = {Talanta},
volume = {305},
number = {},
pages = {129603},
doi = {10.1016/j.talanta.2026.129603},
pmid = {41791354},
issn = {1873-3573},
abstract = {BACKGROUND & AIMS: The quality and market value of the medicinal herb Atractylodes lancea (AL) are critically dependent on its variety, geographical origin, and production mode. To combat adulteration and ensure efficacy, we developed a novel multi-platform analytical strategy integrated with machine learning to establish a robust traceability model for variety discrimination, geographical origin determination, and production mode identification of AL and identify the key chemical indicators responsible for its authentication.

RESULTS: Significant differences were found in trace element concentrations and isotopic ratios among samples. AL's main flavors were spicy, sweet, and fruity, with terpenoids as key aroma contributors. OPLS-DA identified key indicators for tracing AL's variety, including eleven trace elements (e.g., V, Al) and eight volatile compounds (e.g., β-Sesquiphellandrene, 2-Pinen-10-ol). For tracing AL origins, ten trace elements (e.g., Sr, Cr), two stable isotopes (δ[13]C, δ[15]N), five flavor components (e.g., 2-ethyl-3,6-dimethylpyrazine, 2-Pentadecanone), and twenty-six volatile components (e.g., γ-Gurjunene, β-Bisabolene) were identified. Furthermore, three trace elements (Mg, Li and Pb), two isotopes (δ[13]C and δ[15]N), two flavor components (α-Pinene and n-Nonylcyclohexane), and two volatile components (α-Copaene and α-Curcumene) were identified as key indicators for tracing AL's production modes. Finally, among the nine machine learning algorithms evaluated, LightGBM demonstrated superior performance, achieving a traceability accuracy of 95.28 ± 3.01%.

CONCLUSION: The multi-platform data fusion strategy presents a thorough and dependable approach to quality control for Atractylodes lancea. This method establishes a precise, efficient, and adaptable framework, demonstrating substantial potential for application to other high-value botanicals and complex natural products.},
}

@article {pmid41791136,
year = {2026},
author = {Gültekin, M and İlikhan, BA and Baydemir, R and Değirmenci, Y and Başak, AN},
title = {Pathogenic VCP (p.Arg453Trp) variant in three siblings with frontotemporal dementia-amyotrophic lateral sclerosis spectrum: A Turkish family.},
journal = {Clinical neurology and neurosurgery},
volume = {265},
number = {},
pages = {109381},
doi = {10.1016/j.clineuro.2026.109381},
pmid = {41791136},
issn = {1872-6968},
}

@article {pmid41789885,
year = {2026},
author = {Coronas, LE and Timr, S and Sterpone, F and Franzese, G},
title = {Unveiling the entropic role of hydration water in SOD1 partitioning within FUS condensate.},
journal = {The Journal of chemical physics},
volume = {164},
number = {9},
pages = {},
doi = {10.1063/5.0300133},
pmid = {41789885},
issn = {1089-7690},
abstract = {Biological processes such as the sequestration of superoxide dismutase 1 (SOD1) into biomolecular condensates, including fused in sarcoma and stress granules, are vital for understanding disease mechanisms, including amyotrophic lateral sclerosis. Moreover, protein-crowder interactions within these condensates are recognized as fundamental to cellular phase separation and disease-related processes. However, the specific role of the hydration environment in governing SOD1's behavior and transition dynamics within these condensates remains poorly understood, limiting our ability to accurately model these critical biological systems. Therefore, we incorporate explicit water into an implicit solvent model (OPEP) to investigate how water influences SOD1's behavior, residence times, and transition rates among associative states. We employ the advanced CVF (Coronas, Vilanova, Franzese) water model, which accurately captures hydrogen-bond networks at the molecular level. While the OPEP model indicates that bovine serum albumin (BSA) crowders reduce SOD1's partition coefficient (PC) primarily through non-specific interactions, our explicit-water approach points to hydration entropy in BSA as a key contributor to the observed PC reduction. This result offers a new perspective on the system's free-energy landscape, complementing those obtained from OPEP alone. Our research supports the notion that explicitly modeling water can enhance our understanding of protein-crowder interactions and their biological implications, further emphasizing the potential role of water in cellular phase separation and disease-related processes.},
}

@article {pmid41789796,
year = {2026},
author = {Creer, S and Griffiths, AW and Hobson, E and Davies, S and Massey, C and Stokes, L and Waters-Harvey, B and Bamber, R and Hastings, S and Bedford, J and Gould, RL and McDermott, C and Mayberry, E},
title = {"What about me? I'm supposed to be … superhuman?": exploring staff perspectives on how to deliver high quality psychological care for people living with amyotrophic lateral sclerosis.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/17582024.2026.2637420},
pmid = {41789796},
issn = {1758-2032},
abstract = {OBJECTIVES: To explore healthcare professionals' experiences of providing informal psychological care in Amyotrophic Lateral Sclerosis (ALS) services.

METHODS: A qualitative focus group and interview study with 28 UK-based, ALS healthcare professionals. Data was analyzed using reflexive thematic analysis.

RESULTS: Healthcare professionals reported psychological distress in their roles arising from the intrinsic nature of ALS, alongside system factors and their needs as staff members. Participants identified critical needs for themselves to improve psychological care including: psychological skills training, clear role definition, understanding of specialist psychology and structured staff support. Participants identified patient needs as: support for informal carers, access to specialist psychology, clear and inclusive referral pathways, and having person-centered, tiered approaches to care delivery.

CONCLUSIONS: The psychological impact of ALS extends beyond patients and families to healthcare professionals, creating systemic challenges in care delivery. Effective psychological care in ALS requires a comprehensive approach that addresses not only the needs of individual patients but also staff and systemic issues. A distress loop exists where inadequate psychological services affect both staff wellbeing and care quality for patients and their families. Without addressing patient, staff, and service-level issues, people living with ALS and healthcare professionals will continue to experience preventable psychological distress.},
}

@article {pmid41789732,
year = {2026},
author = {Scarpa, E and D'Amora, U and De Cesare, N and Bonadies, I and Dubbioso, R and Nolano, M and Dardano, P and De Stefano, L and Fasolino, A and Zeppetelli, S and Silvestri, A and Zanardi, C and Milella, E and Fasolino, I},
title = {3D Artificial Skin Model As a Novel Strategy for the Detection of Pyroptosis-Cascade Activation in Amyotrophic Lateral Sclerosis.},
journal = {ACS applied materials & interfaces},
volume = {},
number = {},
pages = {},
doi = {10.1021/acsami.5c23366},
pmid = {41789732},
issn = {1944-8252},
abstract = {Amyotrophic lateral sclerosis (ALS) is a severe adult-onset neurodegenerative disease with limited treatment approaches. Evidence has shown that degeneration of cutaneous nerves may reflect neurodegenerative processes occurring within the central nervous system. Although skin biopsy is widely adopted in clinical practice, the procedure is invasive and requires multiple patients' tissue removals. Therefore, we developed a 3D innervated skin model by combining 3D printing of methacrylated hyaluronic acid as an innovative tool for better reproducing the dermis and epidermis and electrospinning of polylactic acid for mimicking skin innervation. Later, 3D artificial skin was colonized with a preneuronal cell line (SH-SY5Y) and fibroblasts isolated from skin biopsy of ALS patients at different disease stages. 3D skin possesses a porosity suitable for cell colonization and a high stability. Importantly, biological results reveal an increase of TAR DNA-binding protein 43 aggregates, NOD-like receptor pyrin domain containing protein 3, interleukin (IL)-18, IL-6, and nitrites in 3D skin of ALS patients, thus indicating pyroptosis activation linked to neurodegeneration. This physiologically relevant 3D skin model reduces the need for repeated biopsies, allows standardized experimental conditions, and supports biomarker research and preclinical drug testing in ALS.},
}

@article {pmid41789116,
year = {2026},
author = {Bublitz, SK and Lorenzl, S and Klima, A and Schmidt, S and Schäffer, B and Gleich, S},
title = {Mapping end-of-life care for patients with neurological conditions in German hospices: a point prevalence survey.},
journal = {BMJ neurology open},
volume = {8},
number = {1},
pages = {e001404},
pmid = {41789116},
issn = {2632-6140},
abstract = {BACKGROUND: Access to palliative care for patients with neurological diseases remains limited. Contributing factors include difficulties in predicting disease trajectories, resource constraints in long-term care and challenges in identifying the end-of-life phase-often compounded by communication and cognitive impairments.

METHODS: We conducted a national point-prevalence survey among German inpatient hospices using an online questionnaire.

RESULTS: The response rate was 44%, with 83% of participating hospices providing complete datasets. Most patients in hospices suffered from oncological diseases (n=785; 77.3%), including primary brain tumours (n=102; 10.0%). At the time of the survey, neurological diagnoses accounted for approximately 5% of hospice admissions. While 51% of hospices reported having access to neurological consultation, this was usually informal or ad hoc. 19% reported no current access to a neurologist but considered such collaboration desirable.

CONCLUSIONS: This survey provides an overview of the current representation of patients with neurological conditions in German inpatient hospices. The findings reveal limited structured collaboration between neurology and palliative care, alongside structural and societal barriers that complicate timely hospice referral and end-of-life planning. Strengthening interdisciplinary cooperation, enhancing neurologists' engagement in palliative care and expanding specialised outpatient support for patients and families are essential to improving equitable and needs-based end-of-life care for individuals with neurological conditions.},
}

@article {pmid41788548,
year = {2026},
author = {Zheng, Y and Zhou, W and Chang, H and Zheng, K},
title = {Brain organoids as precision models for neurodegenerative diseases: from disease modeling to drug discovery.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1764964},
pmid = {41788548},
issn = {1662-4548},
abstract = {Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) have become major global causes of disability and mortality. Their complex pathogenic mechanisms remain incompletely understood, and effective disease-modifying therapies are still lacking. Traditional animal models and two-dimensional (2D) cell culture systems exhibit notable limitations in structural complexity, human relevance, and translational validity, making it difficult to faithfully recapitulate human-specific neuropathology. In recent years, brain organoid technology derived from induced pluripotent stem cells (iPSCs) has advanced rapidly, enabling the self-organization of diverse neuronal and glial cell types within a three-dimensional (3D) architecture that partially mimics human brain development and disease-related pathological events. When integrated with CRISPR-Cas9-based genome editing and multi-omics profiling, organoids support causal mechanism studies, target validation, and individualized drug-response prediction, highlighting their growing value in early-stage drug discovery. Despite current challenges-including insufficient maturation, lack of vascularization and immune components, and batch variability-the continuous progress in bioengineering, microfluidic systems, and artificial intelligence (AI)-driven multimodal data analysis is steadily expanding the translational potential of organoids as human-relevant preclinical models. Overall, brain organoids provide an essential foundation for constructing physiologically relevant and predictive research platforms for neurodegenerative diseases, offering new opportunities for therapeutic development and precision medicine.},
}

@article {pmid41787388,
year = {2026},
author = {Alhathli, E and Cooper-Knock, J and Girach, ZU and Julian, TH and Bauer, C and Timmons, HO and Ward, BD and Walker, H and Azzouz, M and Elrayess, MA and Al-Khelaifi, F and Yousri, NA and Gul, A and Kelsall, A and Moll, T and Harvey, C and Gornall, S and Wong, K and Allen, SP and Strange, A and Shaw, PJ},
title = {Hypothesis-free evaluation of circulating metabolome provides cell-specific insights regarding the role of energy substrate availability in amyotrophic lateral sclerosis.},
journal = {BMC medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12916-026-04727-w},
pmid = {41787388},
issn = {1741-7015},
support = {894-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; 956-799/MNDA_/Motor Neurone Disease Association/United Kingdom ; MR/Z504105/1//UK Research and Innovation/ ; SBF005\1064/AMS_/Academy of Medical Sciences/United Kingdom ; DOD/14/43//My Name'5 Doddie Foundation/ ; NF-SI-0617-10077//National Institute for Health and Care Research/ ; NIHR 203321//NIHR Sheffield Biomedical Research Centre/ ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with limited therapeutic options. The circulating metabolome comprises small molecules present in plasma/serum which are the intermediates and end-products of cellular metabolism, and is linked to ALS pathogenesis.

METHODS: We conducted hypothesis-free two-sample Mendelian randomisation (MR) analysis of the concentration of 575 plasma/serum metabolites, to determine which are causally linked to risk of ALS. Significant metabolites were validated in an independent GWAS of plasma/serum metabolite concentrations and evaluated for sex-specific effects. Correlations between directly measured patient biofluid metabolite concentrations and ALS risk/severity were examined in 94 ALS patients and 40 controls. We experimentally assessed metabolic function in a murine neurons and human astrocytes carrying an ALS-associated G4C2-repeat expansion within C9orf72.

RESULTS: MR causally associated five metabolites with ALS risk after multiple-testing correction. Higher serum concentration of glycoprotein acetyls (P = 9.7e - 9, β = 0.21) and the peptide DSGEGDFXAEGGGVR (P = 8.0e - 6, β = 0.22) was associated with increased ALS risk, whereas higher plasma concentration of phenylalanylserine, isobutyrylcarnitine, and acetylcarnitine was protective (P < 5e - 5, β = - 0.29 to - 0.72). DSGEGDFXAEGGGVR has been linked to glucose metabolism but we have used genetic fine-mapping to link DSGEGDFXAEGGGVR, neuronal glucose uptake through GLUT3, and ALS risk. Direct measurement of metabolite concentrations in patient biofluids revealed elevated acetylcarnitine levels in patients with ALS, which were associated with delayed symptom onset (Cox regression, P = 0.02, HR = 0.4). Similarly, lactate is elevated in ALS patient CSF (ANOVA, P = 1.3e - 3) and in patients with longer survival time (Cox regression, P = 0.03, HR = 0.3). Plasma fructose is elevated in ALS patients with shorter survival time (Cox regression, P = 0.02, HR = 1.1). In vitro, neurons and astrocytes carrying an ALS-associated G4C2-repeat expansion within C9orf72 demonstrated reduced metabolic flexibility.

CONCLUSIONS: We provide evidence that impaired energy substrate availability contributes to ALS risk and severity. CNS cell types differ in their use of energy substrates and therefore we postulate the relative importance of different cell types for different stages of disease. Our findings support further investigation of metabolic interventions to treat or prevent ALS.},
}

@article {pmid41785987,
year = {2026},
author = {Feo, A and Popovic, MM and Faghihi, S and Eshkoly-Lior, T and Tailor, PD and Marin, AI and Santina, A and Choi, WT and Sarraf, D},
title = {Spectrum of Colopathy and Severe Polyposis Associated with Pentosan Polysulfate Sodium Maculopathy: A Retrospective Case Series.},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2026.02.050},
pmid = {41785987},
issn = {1879-1891},
abstract = {OBJECTIVE: To expand the spectrum of gastrointestinal (GI) manifestations associated with pentosan polysulfate sodium (PPS) maculopathy.

DESIGN: Retrospective case series.

SUBJECTS: Eight patients (16 eyes) diagnosed with PPS maculopathy who also underwent GI evaluation between 2019 and 2025.

METHODS: Electronic medical records were reviewed for demographics, PPS dosage and duration, ocular findings, GI history, diagnostic presentation, and histopathology. Multimodal imaging included fundus photography, fundus autofluorescence, fluorescein angiography, optical coherence tomography (OCT), and OCT angiography. Colonoscopy was performed in all patients with histopathologic analysis in selected cases. PPS maculopathy was staged according to Wang et al.'s classification system. Genetic testing was obtained in selected cases to exclude any form of inherited maculopathy or familial adenomatous polyposis.

MAIN OUTCOME MEASURES: Clinical and imaging features of PPS maculopathy and GI pathological diagnosis, including polyposis, dysplasia, and inflammatory bowel disease.

RESULTS: The cohort included 6 women and 2 men (median age: 68.5 years). Median PPS exposure was 25.4 years with a median cumulative dose of 2899 grams. At presentation, 62.5% of eyes were stage 1, 31.3% stage 2, and 6.3% stage 3. At final follow-up, 25% of eyes were stage 1, 50% stage 2, and 25% stage 3. Overall, 37.5% of eyes showed progression of maculopathy stage, and cRORA was present in 75% of eyes at last follow-up. Additional findings included acquired vitelliform lesions, outer retinal tubulations, epiretinal membranes, and type 2 macular neovascularization. Colonoscopy revealed severe adenomatous polyposis in 6 of the 8 patients (75%), with 3 requiring partial or total colectomy and 2 undergoing endoscopic resection. One patient developed ulcerative colitis, and 2 additional patients were diagnosed with Crohn's disease or microscopic colitis. The median latency to GI diagnosis was 10 years after PPS initiation.

CONCLUSIONS: This study expands the recognized systemic toxicity of PPS, demonstrating that PPS maculopathy patients are at risk of concomitant colonic disease, including severe polyposis and dysplasia. The frequent detection of asymptomatic polyposis underscores the importance of colonoscopy screening in exposed patients, even in the absence of GI symptoms. Heightened interdisciplinary awareness and long-term surveillance are warranted to mitigate the vision- and life-threatening consequences of PPS toxicity.},
}

@article {pmid41785403,
year = {2026},
author = {Oh, J and Oh, SI},
title = {Subjective sleep quality in amyotrophic lateral sclerosis: a systematic review and meta-analysis.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/21678421.2026.2614597},
pmid = {41785403},
issn = {2167-9223},
abstract = {OBJECTIVE: Sleep disturbances are common and clinically significant non-motor symptoms in amyotrophic lateral sclerosis (ALS), arising from motor, respiratory, and psychological factors. This study aimed to synthesize available evidence on subjective sleep quality in ALS, estimate the prevalence of poor sleep quality, examine associated factors, and compare patients with healthy controls.

METHODS: : PubMed, EMBASE, Cochrane Central, and CINAHL were searched for studies published between January 2000 and August 2025 that assessed subjective sleep quality in ALS using validated patient-reported outcome measures, such as Pittsburgh Sleep Quality Index (PSQI). Pooled analyses were performed using random-effects models. Meta-regression was applied to explore associations with demographic and clinical variables.

RESULTS: : A total of 23 studies comprising 1899 ALS patients were included, of which 20 were eligible for meta-analysis. All included studies assessed subjective sleep quality using the PSQI, and the pooled mean PSQI score was 6.94, exceeding the clinical cutoff for poor sleep quality. The pooled prevalence of poor sleepers was 56.7%. Nine studies including healthy controls showed significantly higher PSQI scores in ALS patients compared with controls (mean difference 2.69). Several factors, including functional status, depression, anxiety, fatigue, daytime sleepiness, constipation, and cognitive impairment, were associated with poorer sleep, however, meta-regression did not identify significant associations with age, sex, disease duration, or ALSFRS-R.

CONCLUSIONS: : Sleep disturbances are highly prevalent and clinically significant in ALS. These findings highlight the need for systematic screening and proactive management across all stages of the disease. Future research should evaluate a wider range of interventions to improve sleep quality and patient outcomes.},
}

@article {pmid41785396,
year = {2026},
author = {Scirocco, E and Pogemiller Bulat, A and Carey, JR and Giacomelli, E and Boyce, D and Paganoni, S and Berry, JD},
title = {Bridging the gap: understanding participation barriers in ALS clinical trials through on-the-ground insights.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-8},
doi = {10.1080/21678421.2026.2640126},
pmid = {41785396},
issn = {2167-9223},
abstract = {OBJECTIVE: This study explores the experiences and perceptions of people living with amyotrophic lateral sclerosis (pALS), their caregivers, and healthcare providers regarding participation in clinical trials. The study tested the hypothesis, based on existing literature, that geographic distance from multidisciplinary ALS clinics is the primary barrier to awareness and participation in clinical trials.

METHODS: A road trip was conducted to engage individuals, particularly those residing more than 90 miles from specialized clinics. Qualitative and semi-quantitative methods were used to collect data from in-person interviews conducted with pALS, their caregivers, and healthcare providers in urban (high population density), suburban (residential areas on the outskirts of urban centers), and rural (sparsely populated) settings across the East Coast of the US. Thematic analysis was employed to interpret the data.

RESULTS: Based on the interviews, a trusted, supportive, and knowledgeable medical team knowledgeable about ALS research emerged as a critical factor influencing patient participation decisions. Geographic distance alone did not meaningfully impact research interest or awareness. Healthcare providers faced challenges, including time constraints and limited access to updated information about studies, which hindered their ability to promote participation. Healthcare providers cited informal partnerships with advocacy organizations and research centers as crucial for facilitating research participation.

CONCLUSIONS: Tailored communication strategies that leverage established relationships between pALS and their trusted healthcare providers may enhance research participation. As decentralized research models evolve, improving trial education and access and fostering knowledge and trust could significantly boost enrollment in ALS clinical research.},
}

@article {pmid41785390,
year = {2026},
author = {Nomizo, S and Komatsu, J and Shima, A and Muramatsu, D and Matsubara, K and Nozaki, I and Noguchi-Shinohara, M and Nishiyama, A and Suzuki, N and Aoki, M and Ono, K},
title = {Gadolinium enhancement of the cauda equina in a case of familial ALS with p.S135G SOD1 mutation.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-3},
doi = {10.1080/21678421.2026.2638591},
pmid = {41785390},
issn = {2167-9223},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by motor neuron degeneration. Gadolinium enhancement of the cauda equina is typically associated with inflammatory diseases. We report a case of familial ALS with a Cu/Zn superoxide dismutase (SOD1) gene mutation showing marked gadolinium enhancement of the lumbar nerve roots. To date, only a few cases of ALS with gadolinium enhancement of the nerve roots have been reported. To our knowledge, this is the first reported case of ALS with an p.S135G SOD1 mutation exhibiting gadolinium enhancement in the cauda equina.},
}

@article {pmid41785113,
year = {2026},
author = {Rzeszutek, MJ and Regnier, SD and Kaplan, BA and Traxler, HK and Stein, JS and Tomlinson, DC and Koffarnus, MN},
title = {Identification and management of nonsystematic cross-commodity data: Toward best practice.},
journal = {Experimental and clinical psychopharmacology},
volume = {},
number = {},
pages = {},
doi = {10.1037/pha0000836},
pmid = {41785113},
issn = {1936-2293},
support = {//National Institutes of Health; National Institute on Alcohol Abuse and Alcoholism/ ; //National Institutes of Health; National Institute on Drug Abuse/ ; /NH/NIH HHS/United States ; //Food and Drug Administration; Center for Tobacco Products/ ; },
abstract = {Data systematicity has been an important area of consideration for behavioral economic demand. Stein et al. (2015) introduced criteria and an accompanying algorithm to aid researchers in identifying data series that may be considered "nonsystematic"-that is, data that may not follow empirically based assumptions such as an overall decrease in consumption as the cost of a commodity increases and consistency in decreases in consumption. However, those criteria and algorithm are only directly applicable to own-price demand, or demand for a commodity that is increasing in price. Cross-price demand, or demand for a second commodity that changes as a function of some other commodity, does not have a similar set of criteria or algorithm for assessing cross-commodity demand systematicity. Cross-price or cross-commodity demand is useful in understanding how changes in one substance or commodity may change the consumption of another substance or commodity. Thus, we extend Stein et al.'s criteria and algorithm to classify if a cross-commodity can be considered a substitute, complement, or independent, and then assess its systematicity based on its classification. We demonstrate this algorithm on three different cross-commodity demand data sets and describe important considerations regarding data exclusions to prevent biasing results from own-price and cross-price demand. (PsycInfo Database Record (c) 2026 APA, all rights reserved).},
}

@article {pmid41784486,
year = {2026},
author = {Calix Kannaley, K},
title = {Exploring the use of narrative-based approaches in individuals with amyotrophic lateral sclerosis: A narrative review.},
journal = {Palliative & supportive care},
volume = {24},
number = {},
pages = {e81},
doi = {10.1017/S1478951526101965},
pmid = {41784486},
issn = {1478-9523},
abstract = {OBJECTIVES: Narrative-based approaches have been utilized in medicine to better understand the illness experiences of individuals living with chronic conditions. In particular, people with amyotrophic lateral sclerosis (pALS) may benefit from use of narrative-based approaches, given the potential impact of progressive decline on identity of self. This review explores the use of narrative-based approaches in studies involving pALS to provide further insight to the experiences and psychosocial needs of this population.

METHODS: A search was conducted utilizing EMBASE, CINAHL, PsycInfo, and Google Scholar with several terms related to amyotrophic lateral sclerosis (ALS) and narrative-based approaches. Studies were included if they were written in English, incorporated methods that promoted the production of narratives, and reported data that could be clearly isolated to pALS.

RESULTS: The search revealed a total of 154 articles for title and abstract screening. Fifty-two articles were selected for full-text review. Thirty-two articles met the criteria for data extraction. Four descriptive categories emerged upon examination of the narrative-based approaches implemented across the studies: psychosocial intervention, illness experience, intervention targeting specific needs, and secondary analysis of data. Some of the common themes identified across studies included: loss of physical and communicative function, adaptation to life changes, shifts in identity, and tension with the healthcare system.

SIGNIFICANCE OF RESULTS: Despite the communication challenges that often coincide with disease progression, narrative-based approaches can be utilized in pALS. These approaches should be implemented to gain insight on the disease experiences of pALS, providing opportunity for patient-centered interventions to address the psychosocial needs of this population.},
}

@article {pmid41783572,
year = {2026},
author = {Liu, W and Xue, Y and Cao, C and Yang, L and Zhang, L},
title = {Copper Homeostasis and Cuproptosis in Neurological Disorders.},
journal = {Drug design, development and therapy},
volume = {20},
number = {},
pages = {580005},
pmid = {41783572},
issn = {1177-8881},
mesh = {*Copper/metabolism ; Humans ; *Homeostasis ; *Nervous System Diseases/metabolism/drug therapy ; Animals ; },
abstract = {Neurological disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD) pose a serious global public health threat, with complex etiologies involving genetic, environmental, and metabolic factors. Current data indicate that the prevalence of these disorders is rapidly increasing with the aging population, resulting in a growing economic and healthcare burden worldwide. In recent years, the imbalance of copper homeostasis has been increasingly implicated in the pathogenesis of neurological diseases. Copper overload can aggravate neuronal injury by inducing oxidative stress (OS), mitochondrial dysfunction, and protein misfolding, while copper deficiency disrupts the function of copper-dependent enzymes and leads to metabolic abnormalities. The mechanism of cuproptosis, proposed in 2022, describes a novel form of programmed cell death characterized by lipoylated protein aggregation and the loss of Fe-S cluster proteins, offering new insights into copper-related diseases. Multiple studies have demonstrated the crucial role of copper homeostasis and cuproptosis in the onset, progression, and treatment of neurological diseases. This narrative review summarizes the molecular mechanisms involved in copper homeostasis regulation and, on that basis, discusses the role of copper metabolism abnormalities in AD, PD, Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Wilson's disease (WD), Menkes disease (MD), and stroke. Additionally, we highlight the mechanisms of existing copper-regulating drugs and their therapeutic potential in neurological disorders, while pointing out the limitations of current drug development.},
}

*Copper/metabolism
Humans
*Homeostasis
*Nervous System Diseases/metabolism/drug therapy
Animals

@article {pmid41783158,
year = {2025},
author = {Uemura, K and Hiro, S and Attachaipanich, S and Du, R and Yusof, NISM and Kinoshita, M and Hikosaka, M and Ohtsuki, G},
title = {Glioinflammation: disease-associated microglia and astrocytes in psychiatric disorders, neurodegeneration, and senescence.},
journal = {Frontiers in cellular neuroscience},
volume = {19},
number = {},
pages = {1669272},
pmid = {41783158},
issn = {1662-5102},
abstract = {In this review, we synthesize recent conceptual and experimental advances in neuroscience, highlighting selected studies that delineate the roles of reactive microglia and astrocytes in the contexts of developmental inflammatory stress, neurodegenerative diseases, and cellular senescence. Since the characterization of disease-associated glial phenotypes in 2017, building on earlier pioneering discoveries, we focus here on disease-associated microglia (DAM) and disease-associated astrocyte (DAA) to reassess their contributions to glio-inflammation. It is now recognized that the stress-induced glial states are far from uniform; however, the ontogeny, molecular determinants, and functional consequences of this heterogeneity remain incompletely understood, particularly in psychiatric disorders, Alzheimer's disease, and amyotrophic lateral sclerosis. Accordingly, we compare the glial heterogeneity and its underlying mechanisms across translational mouse models and human neuropathology, considering their evolutionary and physiological contexts. While this review does not aim to be exhaustive, we propose an integrative framework that redefines glial stress responses through the combined lenses of inflammation, transcriptomics, mitochondrial dynamics, lipid metabolism, epigenomic regulation, and cellular senescence. Finally, we outline emerging frontiers for AI-enabled multi-omic physiological and pathological approaches, emphasizing their potential to illuminate glial state transitions and accelerate therapeutic discovery in the near future.},
}

@article {pmid41782322,
year = {2026},
author = {Kaya, Y and Kırboğa, KK},
title = {Brain Organoids as Emerging Platforms for Modeling Neurodegenerative Diseases: Progress, Challenges, and Future Directions.},
journal = {Journal of neurochemistry},
volume = {170},
number = {3},
pages = {e70395},
doi = {10.1111/jnc.70395},
pmid = {41782322},
issn = {1471-4159},
abstract = {Neurodegenerative diseases are a group of disorders (such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis) characterized by loss of function and death of neurons in different parts of the nervous system. These pathologies constitute a global burden, especially for aging populations. This circumstance leads to an increasing demand for understanding the fundamental mechanisms and development of therapeutic strategies. Conventional models, including two-dimensional cell culture and animal models, postmortem brain tissue provide an overview about neurodegenerative disorders but do not completely recapitulate cellular and molecular mechanisms of the human brain. Although three-dimensional (3D) brain organoids exhibit similar properties with physiological and pathological conditions of human brain, including interaction of neuronal, glial cells and self-organizing structure, protein aggregation, neuroinflammation, and neuronal degeneration. The integration of reprogrammed human induced pluripotent stem cells (iPSCs) with 3D brain organoid systems provides a clinical platform as a bridge between bench to bedside. Brain organoids have been used to elucidate novel insights into the molecular and genetic mechanisms underlying neurodegenerative diseases. Furthermore, brain organoids serve as a tool for in vitro disease modeling, drug screening and emergence of new treatments. Despite these clinical benefits, there are various limitations such as incomplete tissue maturation, lack of vascularization and incomplete cellular diversity in this 3D culture system. This review describes in detail the advantages and disadvantages of brain organoids usage in modeling neurodegenerative diseases from a contemporary perspective.},
}

@article {pmid41781412,
year = {2026},
author = {Mortimer, AJ and Sander, CF and Parmar, AR and Williams, AJ and Azzouz, M and Hautbergue, GM and Shaw, PJ and Ferraiuolo, L and Mead, RJ},
title = {Comparison of AAV9-driven motor neuron transduction following different CNS-directed delivery methods in mice.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-38039-z},
pmid = {41781412},
issn = {2045-2322},
support = {2023/MNDS/6501/791MEA/MNDA_/Motor Neurone Disease Association/United Kingdom ; 2023/MNDS/6501/791MEA//MND Scotland/ ; },
abstract = {Gene therapies are promising for diseases previously considered incurable. Adeno-associated virus serotype 9 (AAV9) demonstrates remarkable tropism for motor neurons (MNs) and represents an exciting candidate to target genetic causes of motor neuron diseases like amyotrophic lateral sclerosis (ALS). However, systemic delivery risks immunogenicity and off-target effects, therefore localised delivery to the CNS is advantageous. We assessed MN transduction in wild-type post-natal mice using AAV9-controlled, cytomegalovirus-promoter driven, enhanced GFP expression. Intra-cisterna magna (ICM) and intra-cerebroventricular (ICV) methods were compared. Four weeks post-delivery, GFP positivity in MN and astrocytes were quantified via immunohistochemical approaches and viral genome copy number determined by qPCR. All delivery methods achieved high MN transduction in lumbar spinal cord (> 68%). Unilateral ICV delivery provided the highest and most consistent levels (89 ± 3%), and minimal peripheral viral copies. ICV delivery resulted in higher astrocytic transduction, most notably in the cortex. Brainstem MN transduction was high with all methods (> 55%). We failed to find evidence of neuronal transduction in motor cortex. Viral genome copies trended higher in spinal cord and brainstem with ICV approaches, however further work is required to understand how bilateral repeated dose delivery leads to more profound increases. Whilst several routes of administration into cerebrospinal fluid exist, direct comparisons for targeting MNs in vivo remain limited. Overall, all methods of CNS-directed delivery result in high levels of motor neuron transduction in the lumbar spinal cord and brainstem, but not in motor cortex. Unilateral ICV appears to provide the best balance between consistent, high levels of transduction and low off-target effects. However, ICM might be the better option if seeking to avoid astrocytic transduction.},
}

@article {pmid41781384,
year = {2026},
author = {Gunn, AP and Hilton, JBW and Mukherjee, S and Liddell, JR and Mercer, SW and McLean, CA and Masters, CL and Crouch, PJ and Roberts, BR},
title = {Decreased metallothionein-3 expression in the human spinal cord is a common feature of amyotrophic lateral sclerosis and multiple sclerosis.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-025-31283-9},
pmid = {41781384},
issn = {2045-2322},
}

@article {pmid41781371,
year = {2026},
author = {Zhang, L and Huang, Y and Huang, W and Huang, Q and Lin, Y and Gu, J},
title = {TDP-43 phosphorylation: Exploring kinases, phosphatases, and therapeutic potential in neurodegeneration.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261424284},
doi = {10.1177/13872877261424284},
pmid = {41781371},
issn = {1875-8908},
abstract = {TAR DNA-binding protein 43 (TDP-43) is a multifunctional DNA/RNA-binding protein whose abnormal phosphorylation and aggregation are central to the pathogenesis of several neurodegenerative diseases. TDP-43 proteinopathy, characterized by hyperphosphorylation and cytoplasmic accumulation, is a defining pathological feature of amyotrophic lateral sclerosis and frontotemporal lobar degeneration, and is frequently observed in Alzheimer's disease. The phosphorylation state of TDP-43 is dynamically regulated by a network of protein kinases-including CK1, GSK3β, CDC7, and PKA-and counterbalanced by phosphatases such as PP2A and PP1; however, the precise molecular mechanisms governing this equilibrium in disease remain incompletely understood. Notably, phosphorylated TDP-43 acquires prion-like properties, enabling self-templated aggregation and cell-to-cell propagation, which amplifies pathology and drives disease progression. These insights have catalyzed the development of therapeutic strategies aimed at modulating TDP-43 phosphorylation, with kinase inhibitors and phosphatase enhancers emerging as promising candidates for targeting TDP-43 proteinopathies. This review integrates current knowledge on the regulatory networks controlling TDP-43 phosphorylation, examines its role in prion-like spread, and evaluates emerging therapeutic approaches aimed at mitigating TDP-43-mediated neurodegeneration.},
}

@article {pmid41778725,
year = {2026},
author = {Rizvi, FAS and Jimoh, Y and Allouh, MZ and Rahmon, D and Chaudhry, GR},
title = {Mesenchymal stem cell therapies for neurodegenerative diseases: Advancements, challenges, and opportunities.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-01147},
pmid = {41778725},
issn = {1673-5374},
abstract = {Neurodegenerative diseases, including multiple sclerosis, amyotrophic lateral sclerosis, Huntington's disease, retinal degenerative diseases, Alzheimer's disease, and Parkinson's disease, continue to pose a significant clinical challenge due to the progressive loss of neural tissue structure and function. Stem cell-based therapies are gaining attention for the treatment of neurodegenerative diseases. Mesenchymal stem cells, particularly those derived from perinatal tissues, exhibit remarkable plasticity, along with immunomodulatory, neurotrophic, and regenerative capabilities. Mesenchymal stem cells primarily influence their environment through paracrine signaling and can also differentiate into neural lineages, aiding in neuronal repair. Tissue-specific progenitor cells, such as neural stem cells and retinal progenitor cells, offer greater therapeutic precision. This review examines advancements in mesenchymal stem cell-based therapies for neurodegenerative diseases, discusses relevant clinical trials, and highlights the challenges, while proposing that personalized regenerative treatments utilizing lineage-restricted progenitors may improve patient outcomes in these complex disorders.},
}

@article {pmid41778604,
year = {2026},
author = {Ahn, GJ and Cha, KC and Lee, J and Son, YJ and Roh, YI and Jung, WJ and Lee, Y and Im, HY and Hwang, SO},
title = {Comparison of the Hemodynamic Effects of Epinephrine on Blood Pressure Augmentation at 1-, 3-, and 5-Minute Dosing Intervals.},
journal = {Journal of the American Heart Association},
volume = {},
number = {},
pages = {e046743},
doi = {10.1161/JAHA.125.046743},
pmid = {41778604},
issn = {2047-9980},
abstract = {BACKGROUND: Although current cardiopulmonary resuscitation guidelines recommend administering epinephrine at 3- to 5-minute intervals during advanced life support (ALS), scientific evidence for the optimal dosing interval for enhancing hemodynamic parameters remains limited. Therefore, we compared the hemodynamic effects of 1-, 3-, and 5-minute epinephrine dosing intervals on blood pressure augmentation in a porcine ventricular fibrillation cardiac arrest model.

METHODS: Forty-two pigs were randomly assigned to 1-, 3-, and 5-minute epinephrine dosing-interval groups. After ventricular fibrillation induction and a 2-minute downtime, basic life support was initiated with a 30:2 compression-to-ventilation ratio for 8 minutes, followed by 30 minutes of ALS, including asynchronous ventilation at a rate of a single ventilation every 6 seconds, with oxygen delivered at 15 L/min. Epinephrine (0.02 mg/kg) was administered at predetermined intervals of 1, 3, or 5 minutes. We compared the pressure-time integrals for mean blood pressure, coronary perfusion pressure, and diastolic blood pressure among the groups over the 30-minute ALS period.

RESULTS: The mean blood pressure (P<0.001), coronary perfusion pressure (P=0.001), and diastolic blood pressure pressure-time integrals (P=0.005) were significantly higher in the 1-minute group than in the 3- and 5-minute groups. Crucially, mean blood pressure and coronary perfusion pressure pressure-time integrals remained positive in the 1-minute group but became negative in the 3- and 5-minute groups during ALS. The diastolic blood pressure pressure-time integral also remained positive for a longer duration in the 1-minute group.

CONCLUSIONS: A 1-minute epinephrine dosing interval may be significantly more effective in augmenting blood pressure and critical hemodynamic parameters during ALS than are the currently recommended 3- or 5-minute intervals.},
}

@article {pmid41777380,
year = {2026},
author = {, },
title = {Retraction: Enhancing ALS disease management: exploring integrated user value through online communities evidence.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1793079},
doi = {10.3389/fneur.2026.1793079},
pmid = {41777380},
issn = {1664-2295},
abstract = {[This retracts the article DOI: 10.3389/fneur.2024.1393261.].},
}

@article {pmid41777232,
year = {2026},
author = {Yerraguntla, S and Bakshi, B and Chandran, K and Foucher, J and Benatar, M and Wicks, P and Bedlack, R and Shirilla, D and Sun, Y and Maragakis, N and Greenstein, E and Mascias Cadavid, J and Rao, A and Allen, O and Dyckman, K and Wang, O and Beauchamp, M and Chang, V and Brown, A and Carbunar, O and Paganoni, S and Bertorini, T and Pioro, E and Elsharif, B and Jiang, N and Pattee, G and Carter, G and Breevoort, S and Tito, E and Nathaniel, G and Jackson, C and Olby, N and McDermott, C and Ratner, D and Li, X},
title = {ALSUntangled #82: N-acetylcysteine.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-5},
doi = {10.1080/21678421.2026.2638590},
pmid = {41777232},
issn = {2167-9223},
abstract = {N-acetylcysteine is a thiol-containing compound and a precursor of glutathione, with mechanistic plausibility for ALS, including reducing oxidative stress, regulating neuroinflammation, and mitigating mitochondrial dysfunction. Preclinical studies have yielded conflicting results on whether N-acetylcysteine can delay the onset of motor impairment and prolong survival in ALS mouse models. Several case studies of oral or subcutaneous administration of N-acetylcysteine in patients with ALS did not demonstrate convincing benefits. Clinical trials to date have also failed to demonstrate efficacy in slowing ALS progression. While N-acetylcysteine shows theoretical promise, further research is needed to clarify its therapeutic role in ALS. At present, ALSUntangled does not support the use of N-acetylcysteine as a treatment to slow ALS progression.},
}

@article {pmid41776751,
year = {2026},
author = {Roca-Pereira, S and López-Sampere, Y and Mengod-Soler, P and Peña-Fonteboa, M and Marco, C and Caravaca-Puchades, A and Domínguez, R and Vázquez-Costa, JF and Santamaría, E and Fernández-Irigoyen, J and Colomina, MJ and León Moreno, I and Martínez Yélamos, A and Martínez Yélamos, S and Santpere, G and Obis, E and Portero-Otín, M and Piñol-Ripoll, G and Povedano, M and Andrés-Benito, P},
title = {Proteomic profile of CSF obtained at the time of diagnosis determines amyotrophic lateral sclerosis progression and survival: CXCL7 levels in disease prognosis and survival.},
journal = {Brain pathology (Zurich, Switzerland)},
volume = {},
number = {},
pages = {e70089},
doi = {10.1111/bpa.70089},
pmid = {41776751},
issn = {1750-3639},
support = {PI20/000155//Instituto de Salud Carlos III/ ; PI23/00176//Instituto de Salud Carlos III/ ; PI24/01516//Instituto de Salud Carlos III/ ; CD23/00097//Instituto de Salud Carlos III/ ; //Fundació Catalana d'Esclerosi Lateral Amiotròfica (ELA) Miquel Valls/ ; //Elles contra l'Esclerosi Lateral Amiotròfica (ELA)/ ; //Swim for Esclerosi Lateral Amiotròfica (ELA)/ ; //Mà amiga/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease primarily affecting motor neurons. Neurofilament light chain (NfL) is the most established prognostic biomarker; however, its diagnostic resolution is limited, particularly within intermediate concentration ranges, and it does not capture the molecular heterogeneity of ALS. This study aimed to identify complementary cerebrospinal fluid (CSF) biomarkers and pathway-specific signatures through a non-targeted multiomic approach. We performed SWATH-MS-based proteomics and LC-MS/MS lipidomics on CSF from ALS patients stratified by survival (ALS-SS and ALS-LS) and healthy controls. Weighted protein co-expression network analysis (WPCNA) was applied to identify biologically coherent protein modules associated with disease phenotype and progression. Top biomarker candidates were further evaluated using immunoassays in an independent cohort. Post-mortem ALS spinal cord tissues were analyzed to explore the pathophysiological relevance of identified proteins. CSF proteomic profiles robustly distinguished ALS patients from controls and stratified patient subgroups by survival, revealing a molecular signature characterized by inflammation, downregulation of detoxification mechanisms, and synaptic dysregulation in aggressive disease forms. In contrast, lipidomic profiles showed limited discriminatory power. WPCNA identified modular proteomic signatures capturing ALS heterogeneity, and machine learning models based on these profiles yielded optimal biomarker panels for diagnosis and prognosis. CXCL7 emerged as a promising complementary biomarker, and shed light in disease physiopathology. Immunoassay validation supported the diagnostic and prognostic potential of CXCL7 and its association with survival time. Histopathological analysis further confirmed CXCL7 localization in anterior horn motor neurons, despite no detectable changes in whole spinal cord lysates at late disease stages. Comprehensive CSF proteomic profiling, combined with network-based analysis, enhances our understanding of ALS molecular heterogeneity and provides a framework for precision biomarker discovery. CXCL7 complements NfL as a diagnostic and prognostic biomarker, supporting improved patient stratification and advancing the development of personalized therapeutic strategies in ALS.},
}

@article {pmid41776545,
year = {2026},
author = {Krishnamurthy, SS and Buzatto, AZ and Campkin, C and Müller, HP and Wiesner, D and Weishaupt, J and Klose, V and Wiesenfarth, M and Elmas, Z and Herrmann, C and Parlak, Ö and Günther, K and Saad, R and Weiland, U and Dupuis, L and Ludolph, A and Li, L and Kassubek, J and Dorst, J and Roselli, F},
title = {Disruption of the angiopoietin-like system connects lipid homeostasis and hypothalamic dysfunction in ALS.},
journal = {BMC medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12916-026-04749-4},
pmid = {41776545},
issn = {1741-7015},
abstract = {BACKGROUND: Alterations in lipid metabolism are manifestations of amyotrophic lateral sclerosis (ALS) that contribute to the risk and rate of progression. Blood levels of triglycerides and cholesterol are altered in ALS patients and pre-symptomatic gene carriers, but mechanistic insights into these changes are lacking.

METHODS: Serum samples from sporadic ALS patients (n = 118), mutated SOD1 and FUS/TARDBP (n = 20, 40, 17, respectively) with age and gender-matched controls (n = 96) were analysed for alterations in the angiopoietin-like protein (ANGPTL) system using enzyme-linked immunosorbent assays. SOD1[G93A] murine model was studied at pre-symptomatic (P50), early symptomatic (P90), and fully symptomatic (P110) stages, along with their wild-type (WT) littermates for ANGPTLs. Untargeted lipidomics on serum was performed using high-resolution liquid chromatography-mass spectrometry. Further, the involvement of the hypothalamus was studied using hypothalamic volumetry in patients and an antibody array spanning 308 proteins in mice.

RESULTS: We show that mutation-specific patterns of systemic lipid abnormalities appear in ALS and that they correlate with reduced levels of angiopoietin-like proteins 3 and 4. ANGPTL-3/4, in turn, correlates with hypothalamic atrophy but not with corticospinal involvement, as determined by MRI volumetry and diffusion tensor imaging. Lipid phenotype and decreased ANGPTL in humans are recapitulated in two SOD1 murine ALS models, in which ANGPTL-3, -4, and -8 expression patterns are consistent with the repartitioning of lipid utilisation from muscles to the brown adipose tissue; systemic levels of ANGPTL-3 correlate with hypothalamic neuroinflammation and vascular permeability and with hypothalamic levels of agouti-related protein and neuropeptide Y.

CONCLUSIONS: These data provide a molecular mechanism linking peripheral lipid metabolism to the dysfunction of a specific hypothalamic circuit through the mediation of systemic ANGPTL-3 and -4. This finding constitutes a molecularly defined entry point to manipulate lipid metabolism in ALS.},
}

@article {pmid41776544,
year = {2026},
author = {Hirota, R and Lankford, KL and Nakazaki, M and Toyoshima, M and Kocsis, JD},
title = {Intranasal administration of human mesenchymal stromal cell-derived small extracellular vesicles delays disease progression in the SOD1(G93A) mouse model.},
journal = {Molecular brain},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13041-026-01288-0},
pmid = {41776544},
issn = {1756-6606},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron loss, with no established disease-modifying therapy. Mesenchymal stem/stromal cells (MSCs) have been reported to exert neuroprotective effects in models of injury and disease, acting primarily through release of small extracellular vesicles (sEVs). MSC-derived sEVs (MSC-sEVs) have therefore attracted attention as a potential cell-free therapeutic approach for treating neurological conditions such as ALS. Because MSC-sEVs can cross both the nasal epithelial barrier and blood-brain barrier to reach the central nervous system (CNS), intranasal administration represents an attractive approach for repeated delivery of MSC-sEVs for long-term administration. In this study, we administered bone marrow-derived MSC-sEVs or vehicle intranasally to a SOD1(G93A) transgenic mouse model of ALS; the large majority of the sEVs had surface markers for exosomes. Dosing was for three consecutive days per week beginning one day after onset of neurological symptoms and continuing until a moribund state. Neurological score and body weight were recorded daily. Although total survival time and post-onset survival duration were not significantly prolonged by MSC-sEV treatment, MSC-sEV treatment significantly delayed progression from a mild symptom phase (NeuroScore 1) to more severe symptoms (NeuroScore 2) compared with vehicle-treated controls and showed a trend toward slower weight loss. These findings indicate that intranasal administration of MSC-sEVs can delay functional deterioration and prolong the mild impairment stage in an ALS mouse model. If translatable to human patients, such preservation of neurological function could represent a clinically meaningful outcome.},
}

@article {pmid41776147,
year = {2026},
author = {Nowell, WB and McGale, N and Levy, O and Wilding, S and Heinrich, P and Patel, NC and Andrews, JA and Rofail, D},
title = {Exploring the Lived Experiences of Individuals with Amyotrophic Lateral Sclerosis (ALS): A Qualitative Study and Conceptual Model of Signs, Symptoms, and Functional Impacts.},
journal = {Neurology and therapy},
volume = {},
number = {},
pages = {},
pmid = {41776147},
issn = {2193-8253},
abstract = {INTRODUCTION: This study aimed to explore the experience of living with amyotrophic lateral sclerosis (ALS) and to develop a conceptual model for this rare disease.

METHODS: Concept elicitation interviews were conducted (January-September 2024) with people living with ALS (PLwALS; n = 31), caregivers (n = 20), and clinicians (n = 10). Qualitative data were analyzed separately to develop a conceptualization of the experience of living with ALS. Concept saturation was assessed every 5-6 interviews, and a conceptual model was developed.

RESULTS: The mean age of PLwALS was 42.4 years (standard deviation [SD] 11.5), 81% were female, 84% were white, and 23% had SOD1-ALS. The mean time since diagnosis was 4.6 years (SD 4.2); mean normed Rasch Overall ALS Disability Scale score was 76 (SD 17.16). Signs, symptoms, and functions reported during PLwALS interviews included neuromuscular, bulbar, speech, neurocognitive (e.g., memory issues), and a range of physical functioning issues (e.g., motor coordination). PLwALS also reported impacts on a range of activities and psychosocial interactions (e.g., eating, depressed mood, and relationships), alongside management strategies they employed. Interviews with caregivers and clinicians supported findings from the PLwALS interviews. Caregivers also identified signs such as drooling/excess salivation, and impacts related to ALS management (e.g., need for writing aids). Clinicians additionally considered loss of speech and neurocognitive signs (e.g., behavior/personality change) as ALS clinical manifestations. Concept saturation was reached, and a consolidated, comprehensive conceptual model was developed.

CONCLUSION: This research provides a holistic understanding of the experience of living with ALS and is the first conceptual model based on in-depth concept elicitation interviews. The findings highlight the range of signs, symptoms, and impacts that PLwALS experience, emphasizing its serious humanistic impact and high unmet need, and will help to guide patient-centric evaluation of clinical outcome assessments in future ALS studies.},
}

@article {pmid41775600,
year = {2026},
author = {Ding, JY and Li, WX and Wang, J and Huang, CY and Xu, XW and Yang, Q and Liu, XL and Yu, L and Hao, SR and Zhang, HF and Chen, JJ},
title = {Effectiveness of multimodal artificial liver support for acute-on-chronic liver failure: A single-center cohort study.},
journal = {Hepatobiliary & pancreatic diseases international : HBPD INT},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.hbpd.2026.02.001},
pmid = {41775600},
issn = {1499-3872},
abstract = {BACKGROUND: Multimodal artificial liver support (ALS) has been proven to be effective in a porcine model of acute liver failure. This study aimed to evaluate the curative effect in patients with acute-on-chronic liver failure (ACLF).

METHODS: Data from ACLF patients receiving multimodal ALS between January 2014 and August 2019 were collected. Patients were divided into two groups according to the patterns of ALS: a trimodal ALS group (trimodal group) and a bimodal ALS group (bimodal group). A propensity score matching was performed to control for baseline bias between the groups. Survival rates and laboratory parameters were compared after single session and after completion of all the sessions of treatments.

RESULTS: A total of 182 patients undergoing multimodal ALS were screened. Propensity score matching generated 47 pairs. The short-term (28/90 days) survival rates were significantly higher in the trimodal group than those in the bimodal group (28-day survival rate: 91.5% vs. 76.6%, P = 0.049; 90-day survival rate: 91.5% vs. 74.5%, P = 0.027). The model for end-stage liver disease score was improved both after single session and after completion of all the sessions of treatments. Single session of trimodal ALS significantly reduced bilirubin (P < 0.001) and bile acid (P = 0.003) levels compared with bimodal ALS. Compared with baseline, gamma-glutamyltransferase (P = 0.001) and alkaline phosphatase (P = 0.021) levels were significantly decreased after completion of all the sessions of treatments in the trimodal group. However, no significant differences were observed in these two parameters within the bimodal group. Trimodal ALS was associated with increased clearance rates of interleukin-8 (P = 0.009) and macrophage migration inhibitory factor (P = 0.012). Multivariate Cox regression revealed that trimodal ALS was an independent predictor of lower 28- and 90-day mortality (both P < 0.05).

CONCLUSIONS: Trimodal ALS may provide a greater survival benefit for patients with ACLF, likely because of its superior ability to clear toxic substances and suppress inflammation.},
}

@article {pmid41775321,
year = {2026},
author = {Lu, YH and Zhu, XP and Li, S and Zhang, FN and Cai, CB and Tian, M and Zhu, YH and Zeng, LH and Tan, J and Yu, CY and Chen, J},
title = {From scaffold to effector: reframing GFAP in neurodegeneration.},
journal = {Journal of advanced research},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jare.2026.02.051},
pmid = {41775321},
issn = {2090-1224},
abstract = {BACKGROUND: Neurodegenerative disorders impose a growing global burden, yet disease-modifying therapies remain limited. Glial fibrillary acidic protein (GFAP) has shifted from a passive astrocytic marker to an active effector that shapes neurodegenerative pathology.

AIM: of Review: This review synthesizes mechanistic and translational evidence that defines GFAP as a proteoform-governed hub and highlights its value for biomarker-guided precision intervention. Key Scientific Concepts of Review: An extensive literature search across major databases was conducted using predefined keywords and strict inclusion criteria, covering mechanistic, pathological, and clinical studies. Evidence supports a GFAP proteoform code in which alternative splicing generates functionally distinct isoforms, and PTMs encode context-dependent assembly dynamics and signaling outputs. We summarize how GFAP proteoforms integrate cytoskeletal remodeling with inflammatory transcriptional programs (notably STAT3 and NF-κB), proteostasis stress, and mitochondrial dysfunction, thereby coupling astrocyte state transitions to neuronal vulnerability and synaptic impairment. Disease trajectories are context-specific: GFAP dysfunction drives primary toxicity in Alexander disease (AxD); in Alzheimer's disease (AD), isoform-specific mechanisms intersect with amyloidogenic machinery and track early preclinical astrocyte activation; and in frontotemporal dementia (FTD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), GFAP reflects inflammatory-metabolic coupling during progression. Translationally, ultrasensitive plasma assays reveal GFAP elevation years to decades before symptom onset, complementing NfL and amyloid/tau within AT(N)-oriented diagnostic frameworks. Therapeutically, we evaluate precision strategies beyond global suppression, including ASO-based modulation, targeting STAT3/NF-κB-driven reactive programs, and restoring proteostasis via chaperone/autophagy pathways. Future progress hinges on isoform-/PTM-specific probes, conformational sensors, and spatial proteomic atlases validated in prospective longitudinal cohorts. In conclusion, GFAP represents both a mechanistic driver and a scalable biomarker, offering a translationally actionable axis to advance precision medicine in neurodegeneration.},
}

@article {pmid41775065,
year = {2026},
author = {Esmaeili, A and Dashtian, K and Zare-Dorabei, R and Kerman, K and Mahdavi, M},
title = {A tri-responsive sensor based on co-encapsulated organic probes and multifunctional bimetallic V/Ce-MOF nanozyme in a hydrogel for the detection of l-Serine in saliva.},
journal = {Talanta},
volume = {305},
number = {},
pages = {129594},
doi = {10.1016/j.talanta.2026.129594},
pmid = {41775065},
issn = {1873-3573},
abstract = {Rapid and accurate detection of l-Serine, a key potential biomarker of neurological diseases such as Alzheimer, Parkinson and Amyotrophic lateral sclerosis (ALS) disease, is crucial for public health. Herein, we prepared a tri-responsive sensor capable of colorimetric, fluorimetric, and electrochemical detection. This portable sensor integrates co-encapsulated organic probes with a multifunctional bimetallic cerium/vanadium metal-organic framework (UiO-66-NH2(Ce/V)) nanozyme activity, all embedded within a biocompatible agarose-based hydrogel for detection of l-serine in a saliva sample. Physicochemical and electrochemical analyzes confirmed that the UiO-66-NH2(Ce/V) nanozyme, with peroxidase-like activity, facilitated the oxidation of tetramethylbenzidine (TMB) in the colorimetric assay, ortho-phenylenediamine (OPD) in the fluorometric assay and TMB in the electrochemical assay. The oxidation of these probes resulted in the formation of colored compounds in the colorimetric and fluorometric sensors, as well as created sharp anodic peaks in the electrochemical sensors via Vmax of 3.99 M[-1], 5.85 M[-1] and 0.002 M[-1], respectively. The results prove that increasing the concentration of l-serine inhibited the oxidation-reduction reactions, causing a reduction in the intensity of both the colors and the sensor peaks. It demonstrated a wide linear detection range of 5 to 250 μM for the colorimetric sensor, 1-250 μM for the fluorometric sensor, and 0.3-250 μM for the electrochemical sensor with a detection limit of 0.27 μM, 0.26 μM, and 0.076 μM, respectively. These sensors were applied to the detection of l-serine in human saliva samples, achieving recovery rates between 92.20% and 107.50% with RSD of <5%, and excellent reproducibility. The findings suggest that these sensors have significant potential for use in hospitalized healthcare systems to monitor disease biomarkers and represent a promising approach for early diagnosis of disease.},
}

@article {pmid41773017,
year = {2026},
author = {Liang, X and Zhao, T and Dai, X and Sun, Y and Yuan, J and Afzalpurkar, S and Duong, C and Yu, A and Tang, F and He, X and Liu, X and Chen, X and Cao, Z and Wang, Y},
title = {FUS is an N1- and N6-methyladenosine-binding protein.},
journal = {Nucleic acids research},
volume = {54},
number = {5},
pages = {},
pmid = {41773017},
issn = {1362-4962},
support = {R35 ES031707/NH/NIH HHS/United States ; T32 ES018827/NH/NIH HHS/United States ; R35 ES031707/NH/NIH HHS/United States ; },
mesh = {*RNA-Binding Protein FUS/metabolism/genetics ; Humans ; *Adenosine/analogs & derivatives/metabolism ; Methyltransferases/metabolism/genetics/antagonists & inhibitors ; Methylation ; Cell Line, Tumor ; Amyotrophic Lateral Sclerosis/genetics/metabolism ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/metabolism/genetics ; Protein Binding ; },
abstract = {Nucleotide repeat expansions contribute to a number of neurological disorders. Mutations and augmented expression in fused in sarcoma (FUS) can result in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Here we reveal that FUS is an N1- and N6-methyladenosine (m1A- and m6A)-binding protein, where the protein interacts with the methylated adenosines in CAG repeat expansion RNA, thereby leading to the protein's cytoplasmic redistribution in SH-SY5Y cells. We also found that ectopically expressed FUS co-localizes with CAG repeat RNA in the cytosol. This co-localization is diminished upon genetic depletion of m6A and m1A writer proteins (i.e. METTL3 and TRMT61A), pharmacological inhibition of METTL3, and ectopic overexpression of m1A and m6A eraser proteins (i.e. ALKBH3 and FTO). Moreover, binding to methylated CAG repeat RNA renders the ectopically expressed FUS protein less dynamic in cells. Together, our study underscores a critical role for m1A and m6A in enhancing FUS-RNA interaction, which results in aberrant subcellular distribution and attenuated mobility of the protein in cells. These findings unveil a novel mechanism underlying neurodegenerative disorders emanating from elevated expression of FUS and suggest targeting FUS-methylated adenosine interactions as a potential therapeutic strategy for FUS proteinopathy.},
}

*RNA-Binding Protein FUS/metabolism/genetics
Humans
*Adenosine/analogs & derivatives/metabolism
Methyltransferases/metabolism/genetics/antagonists & inhibitors
Methylation
Cell Line, Tumor
Amyotrophic Lateral Sclerosis/genetics/metabolism
Alpha-Ketoglutarate-Dependent Dioxygenase FTO/metabolism/genetics
Protein Binding

@article {pmid41772759,
year = {2026},
author = {Donega, S and Gorospe, M and Harries, LW and Ferrucci, L},
title = {Loss of Splicing Homeostasis as a Hallmark of Aging.},
journal = {Molecular and cellular biology},
volume = {},
number = {},
pages = {1-19},
doi = {10.1080/10985549.2026.2627235},
pmid = {41772759},
issn = {1098-5549},
abstract = {Alternative splicing is a fundamental mechanism that ensures accurate gene expression, supports cellular adaptability, and expands protein diversity beyond the limits of a fixed gene pool. With aging, splicing fidelity weakens, contributing to decline in RNA homeostasis and disrupting essential cellular functions, including mitochondrial oxidative phosphorylation, genome stability, and immune regulation, and in turn accelerating tissue and organ dysfunction. Evidence from senescent cells, aged tissues, and model organisms shows that altered levels of splicing factors and increased RNA polymerase II elongation rates impair co-transcriptional splicing and promote mis-spliced isoforms that reinforce senescence and drive pathology. Dysfunction of RNA-binding proteins further contributes to aberrant splicing, linking splicing defects to age-related diseases such as atherosclerosis, osteoarthritis, sarcopenia, and neurodegenerative disorders like Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Therapeutic strategies to correct splicing defects, such as antisense oligonucleotides, RNA interference, CRISPR-Cas systems, ADAR-mediated editing, and RNA aptamers, can restore a homeostatic balance of mRNA isoforms. However, major challenges remain, including distinguishing adaptive physiological from pathological splicing 'noise' and achieving targeted delivery to tissues. Despite these obstacles, RNA splicing dysregulation represents a promising avenue to extend health span by reestablishing homeostatic RNA programs, and reinforces the idea that "transcriptomic instability" is a hallmark of aging.},
}

@article {pmid41772409,
year = {2026},
author = {Sorenson, E and Heitzman, D and Lee, I and Jang, G and Elman, L and Habib, AA and Wymer, J and Hayat, G and Goutman, SA and Fernandes, JAM and Floeter, MK and Ajroud-Driss, S and Gwathmey, K and Kasarskis, E and Kisanuki, YY and Lomen-Hoerth, C and Walk, D and Johnston, WS and Diaz, F and Maragakis, NJ and Paganoni, S and Shah, J and Oskarsson, B and Zinman, L and Heiman-Patterson, T and Jawdat, O and Fournier, CN and Pulley, MT and Scelsa, SN and Shoesmith, C and Simmons, Z and Sherman, AV and Hoover, BN and Yun, RY and Cheung, K and Mitsumoto, H and , },
title = {Prospective Validation of the New PLS Diagnostic Criteria From PLS Natural History Study: EMG and Neurofilament Analyses.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70192},
pmid = {41772409},
issn = {1097-4598},
support = {//Mr. David Marren and family/ ; //Spastic Paraplegia Foundation/ ; //ALS Association/ ; //Mitsubishi Tanabe Pharma Corporation/ ; //Muscular Dystrophy Association/ ; //Wings over wall street/ ; //Sean M. Healey and AMG center for ALS research/ ; },
abstract = {BACKGROUND: Primary lateral sclerosis (PLS) is an ultrarare upper motor neuron syndrome with a prognosis unique from classical ALS. The study of PLS is complicated by its rarity and the difficulty distinguishing PLS from ALS. We present data from a 1-year prospective follow-up study on PLS and efforts to distinguish it from ALS.

METHODS: Seventy-six PLS participants enrolled in this prospective natural history study. EMG studies, blood neurofilament light chain levels (NfLs), and demographic characteristics were obtained at baseline. At 1-year follow-up, repeat EMG studies were conducted to determine which participants fulfilled criteria for ALS. Baseline characteristics were then compared to determine features that predict reclassification.

RESULTS: Seventy participants completed 1-year follow-up. Five of the 70 were reclassified to ALS (7.1%). Those reclassified had higher trends in baseline blood NfL levels (91.4 vs. 34.0 pg/mL, p = 0.13) and shorter symptom duration (39 vs. 69 months in the PLS group, p = 0.15). Reclassification was noted in both probable and definite PLS participants. All cases with a symptomatic duration of less than 2 years retained the PLS phenotype (5 of 5). NfL levels over 90 pg/mL predicted reclassification with 94% specificity and 60% sensitivity. No other features predicted reclassification to ALS.

CONCLUSIONS: In our population, reclassification of PLS to ALS occurred at a low frequency at 1 year follow-up (7.1%). Baseline NfL was the strongest predictor in differentiating UMN dominant ALS from PLS at 1-year follow-up. Based on our data, we propose EMG and NfL criteria for enrollment in future PLS trials.},
}

@article {pmid41772347,
year = {2026},
author = {Ahuja, V and Sahu, B and Khurana, S and Kumari, K and Ganguly, NK and Gourie-Devi, M and Verma, S and Dastidar, SG and Taneja, V},
title = {Granules Gone Rogue: Nuclear and Cytoplasmic Ribonucleoprotein Structures in Amyotrophic Lateral Sclerosis-Fused in Sarcoma (ALS-FUS) Pathology.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {41772347},
issn = {1559-1182},
support = {211610027970//University Grants Commission/ ; EMDR/IG/9/2024-01739//Indian Council of Medical Research/ ; 3/1/2/151/Neuro/2021-NCD-I//Indian Council of Medical Research/ ; IIRPIG-2023-0001508//Indian Council of Medical Research,India/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/pathology/metabolism/genetics ; Humans ; *RNA-Binding Protein FUS/metabolism/genetics ; *Cytoplasmic Granules/metabolism/pathology ; Animals ; *Ribonucleoproteins/metabolism ; *Cell Nucleus/metabolism ; *Cytoplasm/metabolism ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the selective loss of motor neurons. Among its genetic subtypes, mutations in the fused in sarcoma (FUS) gene represent an aggressive form, often associated with early onset and rapid progression. FUS is a ubiquitously expressed DNA/RNA-binding nuclear protein involved in maintaining DNA damage repair and RNA metabolism. It also plays a crucial role in the formation of ribonucleoprotein (RNP) granules such as cytoplasmic stress granules and nuclear paraspeckles under stress. In ALS, pathogenic FUS mutations frequently disrupt the subcellular distribution of FUS, leading to cytoplasmic mislocalization and aggregation. Mutant FUS further disrupts granular dynamics by its aberrant incorporation into stress granules and altering their biophysical properties. The loss of nuclear FUS function leads to elevated levels of the long non-coding RNA NEAT1 and enhanced paraspeckle assembly with disrupted structural integrity. The impaired nucleocytoplasmic granular dynamics compromise the cellular resilience, thereby increasing motor neuron vulnerability. The interaction of FUS with other ALS-associated proteins causes pathological alterations in the cellular milieu, suggesting a common underlying disease mechanism. This comprehensive review emphasizes the FUS-mediated RNP granule regulation under physiological and pathological conditions. Further, clinically approved and emerging therapeutic strategies aimed at attenuating FUS pathology and RNP granule dynamics have been described.},
}

*Amyotrophic Lateral Sclerosis/pathology/metabolism/genetics
Humans
*RNA-Binding Protein FUS/metabolism/genetics
*Cytoplasmic Granules/metabolism/pathology
Animals
*Ribonucleoproteins/metabolism
*Cell Nucleus/metabolism
*Cytoplasm/metabolism

@article {pmid41772317,
year = {2026},
author = {Weller, B and Lin, CW and Rothballer, S and Calderwood, MA and Falter-Braun, P and Falter, C},
title = {NeuroViOme: a viral orfeome collection for studies of neurodegenerative disease.},
journal = {Journal of neurovirology},
volume = {32},
number = {2},
pages = {},
pmid = {41772317},
issn = {1538-2443},
mesh = {Humans ; *Neurodegenerative Diseases/virology/genetics/pathology ; *Host-Pathogen Interactions/genetics ; *Viral Proteins/genetics/metabolism ; *Open Reading Frames/genetics ; Animals ; Virus Replication/genetics ; },
abstract = {Neurodegenerative diseases such as Alzheimer's and Parkinson's disease, Amyotrophic Lateral Sclerosis (ALS), and Multiple Sclerosis (MS) pose a global health challenge due to their progressive course and lack of curative therapies. These conditions lead to severe neurological decline, significantly impacting patient independence and quality of life, and ultimately result in lethal outcome. Emerging evidence suggests that viral infections contribute to the onset and progression of these neurological diseases, Leblanc and Vorberg (PLoS Pathog 18:e1010670, 2022), either by directly inducing neurological symptoms or by triggering immune responses resulting in neuropathology. Nevertheless, systematic studies of the direct interplay between viral and host proteins in neurodegeneration remain scarce. A key aspect of viral pathogenesis is direct interaction between viral and host proteins (protein-protein interactions, PPIs), which are essential for viral replication and can disrupt or redirect host cell function Kim et al. (Nat Biotechnol, 2022); Zhou et al. (Res Sq, 2022), potentially contributing to the development of diseases traditionally considered non-communicable. Understanding these molecular mechanisms is crucial for advancing diagnostic and therapeutic strategies in neurodegenerative conditions, particularly ALS and MS. To enable systematic studies of these interactions, we introduce NeuroViOme as ORFeome resource encompassing nearly all protein-coding sequences from nine viruses selected based on their prevalence, neurotropism, and mechanistic or epidemiological links to neurodegenerative processes. NeuroViOme includes ORFs from Enteroviruses (EV-A71, EV-D68, CVB3, Echovirus E30), Herpesviruses (HSV-1, EBV, HHV3/Varicella Zoster), the endogenous retrovirus HERV-K, and Polyomavirus JCPyV. To our knowledge, this represents the most comprehensive viral ORF set assembled for neurodegeneration research to date. The collection builds the foundation for interactome mapping and functional genomics analyses and provides a valuable basis for systematic studies of viral perturbations of host pathways.},
}

Humans
*Neurodegenerative Diseases/virology/genetics/pathology
*Host-Pathogen Interactions/genetics
*Viral Proteins/genetics/metabolism
*Open Reading Frames/genetics
Animals
Virus Replication/genetics

@article {pmid41772227,
year = {2026},
author = {Rizzo, GEM and Vanella, G and Fuccio, L and Facciorusso, A and Mazza, S and Catena, F and Fabbri, C and Anderloni, A and Tarantino, I},
title = {Endoscopic ultrasound-guided gastrointestinal anastomoses for the treatment of afferent limb syndrome: a systematic review and meta-analysis.},
journal = {Surgical endoscopy},
volume = {},
number = {},
pages = {},
pmid = {41772227},
issn = {1432-2218},
abstract = {BACKGROUND AND STUDY AIMS: Afferent limb syndrome (ALS) is a rare condition resulting in a mechanical obstruction in the afferent loop after surgical gastrointestinal (GI) reconstruction. Endoscopic ultrasound (EUS)-guided gastrojejunostomy (GJ) or jejunojejunostomy (JJ) is increasing in clinical practice. Therefore, the aim of this systematic review with meta-analysis is to evaluate the efficacy and safety of EUS-GJ or EUS-JJ for ALS.

PATIENTS AND METHODS: The most important medical databases were systematically searched through May 2025. The primary outcome was technical success of EUS-GJ/JJ for ALS. Secondary outcomes were clinical success, safety, and recurrence rate. A random-effects model was used to pool the results. Heterogeneity was expressed as inconsistency index (I[2]) and explored through subgroup analyses.

RESULTS: 9 studies (all retrospective) involving 188 patients were included in the analysis. The weighted mean age was 65.38(± 10.57) years and the etiology of the ALS was mostly malignant. Technical success was 96.3% (CI95% 93.2-99.4%, I[2] = 0%). Clinical success was 95% (CI95% 91.2-98.7%, I[2] = 0%) and adverse events (AEs) rate was 6.9% (CI95% 2.9-11.1%, I[2] = 0%). Recurrence rate was 16.6% (CI95% 7.7-25.4%, I[2] = 43.79%). Subgroup analyses showed differences in the recurrence rate between the use of a fully covered self-expandable metal stent (FCSEMS) (35.9% [CI95% 20.3-51.6%, I[2] = 0%]) and a lumen-apposing metal stent (LAMS)(10.4% [CI95% 4-16.8%, I[2] = 0%], p = 0.003). Follow-up ranged from a median of 96.5 to 185 days.

CONCLUSIONS: EUS-guided GI anastomosis is an effective treatment for ALS, showing high technical and clinical success rates and a low incidence of AEs. The use of LAMS over FCSEMS seems to reduce the recurrence rate, suggesting the routine use of LAMS in the case of EUS-guided GI anastomosis for treating ALS.},
}

@article {pmid41769387,
year = {2026},
author = {Scirocco, E and Scalia, J and Ugolini, B and Casagrande, G and Ho, D and Hagar, JL and Kingsley, K and Hoffman, R and Cooley, C and Cudkowicz, ME and Paganoni, S and Berry, JD},
title = {The Amyotrophic Lateral Sclerosis House Call Program: A Single-Center Experience in the United States.},
journal = {Neurology research international},
volume = {2026},
number = {},
pages = {6629960},
pmid = {41769387},
issn = {2090-1852},
abstract = {BACKGROUND: Accessing multidisciplinary care poses challenges for people living with amyotrophic lateral sclerosis (ALS) due to mobility issues. As ALS care rarely requires hospital-based technology, most care is available through home visits. The Daniella Lipper ALS House Call Program (HCP) at Massachusetts General Hospital (MGH), launched in 2017 in collaboration with Compassionate Care ALS, has pioneered home-based ALS care in Eastern Massachusetts.

METHODS: A retrospective chart review of ALS and primary lateral sclerosis (PLS) patients enrolled in the HCP at MGH was conducted. Data on demographics, visit details, and procedures performed during home visits were collected from electronic health records for patients seen from January 2024 to December 2024.

RESULTS: In 2024, the ALS HCP conducted 959 visits for 142 patients (average age: 68 years, range: 36-93; 47.9% female). Of these patients, 137 (96.5%) were diagnosed with ALS and 5 (3.5%) with PLS. Notably, 61 patients (43%) received care exclusively at home. Key interventions included 44 gastrostomy tube exchanges and 59 respiratory assessments, both of which significantly reduced hospital visits. The average distance traveled by the care team was 30.32 miles per visit.

CONCLUSIONS: The Daniella Lipper ALS HCP at MGH brings ALS expertise into the patient's home, minimizing travel burdens and ensuring continuity of care. The program illustrates the feasibility and impact of home-based ALS care, suggesting potential for broader implementation across the nation. Development will focus on expanding services, such as tracheostomy changes in the homes, and on creating sustainable models for similar initiatives.},
}

@article {pmid41768770,
year = {2026},
author = {Perlatti, B and Vellanki, S and Zhang, Y and Chiang, YM and Hu, Y and Yuan, M and Dunbar, K and Fine, A and Grau, MF and Li, S and O'Donnell, T and Shenoy, R and Li, H and Shi, H and Xu, X and Chen, Z and Arvedson, T and Tang, Y and Cramer, RA and Cee, V and Harvey, CJB},
title = {An Antifungal with a Novel Mechanism of Action Discovered via Resistance Gene-Guided Genome Mining.},
journal = {ACS central science},
volume = {12},
number = {2},
pages = {197-207},
pmid = {41768770},
issn = {2374-7943},
abstract = {Invasive fungal infections claim over two million lives annually, a problem exacerbated by rising resistance to current antifungal treatments and an increasing population of immunocompromised individuals. Despite this, antifungal drug development has stagnated, with few novel agents and fewer novel targets explored in recent decades. Here, we validate acetolactate synthase (ALS), an enzyme critical for branched-chain amino acid biosynthesis and absent in humans, as a promising target for new therapeutics. Using resistance gene-guided genome mining, we discovered a biosynthetic gene cluster in Aspergillus terreus encoding HB-35018 (1), a novel spiro-cis-decalin tetramic acid that potently inhibits ALS. Biochemical and antifungal assays demonstrate that 1 surpasses existing ALS inhibitors in efficacy against Aspergillus fumigatus and other pathogenic fungi. Structural studies via cryo-electron microscopy reveal a unique covalent binding interaction between compound 1 and ALS, distinct from known inhibitors, and finally, we demonstrate that ALS is essential for virulence in a mouse model of invasive aspergillosis. These findings position ALS as a promising target for antifungal development and demonstrate the potential of resistance gene-guided genome mining for antifungal discovery.},
}

@article {pmid41768173,
year = {2026},
author = {Capitani, G and Lozzi, D and Curcio, G and Migliore, S},
title = {Moral decision-making in patients with neurodegenerative diseases: a systematic review.},
journal = {Frontiers in psychology},
volume = {17},
number = {},
pages = {1745923},
pmid = {41768173},
issn = {1664-1078},
abstract = {INTRODUCTION: Moral decision-making, a core component of social cognition, relies on integrating affective and cognitive processes supported by distributed neural networks. Neurodegenerative diseases disrupt these systems to varying degrees, offering unique models to investigate the neural bases of moral cognition. This review aimed to systematically examine moral decision-making deficits across neurodegenerative diseases, delineate disease-specific patterns of moral cognition impairment, and highlight conceptual and methodological gaps to inform future research and clinical assessment.

METHODS: A systematic search of PubMed, Web of Science, and Scopus was conducted for studies published up to January 2025, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines.

RESULTS: Seventeen studies met inclusion criteria. Convergent evidence indicates that behavioral variant frontotemporal dementia (bvFTD) produces a distinctive utilitarian bias characterized by diminished empathy, emotional blunting, and impaired integration of intention and outcome, reflecting degeneration of the ventromedial prefrontal cortex, anterior insula, and amygdala within the salience and default mode networks. In contrast, Alzheimer's disease (AD) patients typically preserve affective aversion to harm, suggesting relative sparing of limbic-ventromedial circuits despite conceptual and executive decline. Moral reasoning in Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS) remains largely intact unless frontotemporal involvement occurs, while dementia with Lewy bodies (DLB) manifests intermediate profiles marked by reduced cognitive theory of mind and aberrant moral affect.

DISCUSSION: These findings delineate disease-specific patterns of moral dysfunction linked to network-level degeneration rather than global cognitive decline. Understanding these mechanisms holds translational relevance for early diagnosis, ethical capacity assessment, and the development of ecologically valid tools to monitor socio-emotional deterioration in neurodegenerative disorders.},
}

@article {pmid41768026,
year = {2026},
author = {Porges, SW},
title = {When A Critique Becomes Untenable: A Scholarly Response To Grossman Et Al.'S Evaluation Of Polyvagal Theory.},
journal = {Clinical neuropsychiatry},
volume = {23},
number = {1},
pages = {113-128},
pmid = {41768026},
issn = {2385-0787},
abstract = {A recent critique advanced by Grossman et al. (2026, this issue) argues that Polyvagal Theory is scientifically untenable, asserting that its core claims regarding autonomic organization, respiratory sinus arrhythmia (RSA), and evolutionary framing are inconsistent with established neurophysiology. The present paper evaluates these assertions not by disputing individual claims in isolation, but by examining whether the critique engages Polyvagal Theory as it is articulated in the peer-reviewed literature and whether it meets the epistemic standards required for scientific refutation. Rather than responding sequentially to individual objections, the analysis clarifies the theory's conceptual foundations, scope, and explicit conditions of falsifiability as a systems-level, pathway-specific framework of autonomic state regulation. It demonstrates that the critique repeatedly evaluates a reconstructed proxy of the theory shaped by persistent category errors, including conflation of neuroanatomy with neurophysiology, reduction of theory to measurement, and substitution of phylogenetic continuity for functional organization. These structural misrepresentations propagate across methodological, neurophysiological, evolutionary, and developmental domains, precluding meaningful empirical adjudication. Across these domains, the paper shows that disagreements concerning RSA metrics, comparative anatomy, or evolutionary framing do not engage the theory's specified mechanisms or demonstrate conditions under which its predictions would fail. Where disagreement exists, it reflects differences in measurement preference, level of analysis, or theoretical framing rather than evidence against the theory's organizing principles. An appendix presents a historical audit showing that several central claims reiterated in the critique were identified in the literature nearly two decades earlier as mischaracterizations of Polyvagal Theory. Their continued repetition without substantive modification reflects a persistent failure of representational uptake rather than unresolved empirical controversy. It is concluded that the charge of scientific untenability does not apply to Polyvagal Theory as formulated, but instead reflects a critique that fails to engage the theory on its own terms. Productive scientific discourse requires representational fidelity, appropriate alignment of levels of analysis, and responsiveness to theoretical and empirical clarification ‒ criteria essential to theory evaluation but not met in the critique under review.},
}

@article {pmid41767843,
year = {2026},
author = {Ben Khalaf, N},
title = {Heat shock proteins (Hsp70 and Hsp90) in neurodegeneration: pathogenic roles and therapeutic potential.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1711422},
pmid = {41767843},
issn = {1663-4365},
abstract = {The maintenance of protein homeostasis is essential for neuronal survival and function; however, it progressively declines with age, predisposing the brain to neurodegenerative diseases. Molecular chaperones Hsp70 and Hsp90 are key guardians of proteostasis, pivotally regulating protein folding, refolding, and degradation under both physiological and stress conditions. This review integrates an overview of the structural features, isoforms, and mechanistic interactions of Hsp70 and Hsp90. It highlights how their dysfunction contributes to the pathogenesis of major neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. We first examine the architecture and ATP-driven chaperone cycles of Hsp70 and Hsp90, their co-chaperone networks, and the feedback regulation by the Heat Shock Factor-1 pathway. We then discuss evidence linking age-related declines in chaperone expression and HSF-1 activity to proteostasis collapse and neuronal vulnerability. The review particularly examines how Hsp70 and Hsp90 differentially influence pathogenic protein aggregation (e.g., tau, α-synuclein, TDP-43, and mutant huntingtin) and how this balance is altered in the aging brain. Regarding therapeutic approaches, we summarize current strategies targeting these chaperones, including small-molecule modulators of Hsp70 and Hsp90, co-chaperone inhibitors, and recombinant chaperone therapy, which has shown to restore proteostasis and cognitive function in experimental models. These emerging interventions underscore the dual nature of Hsp70/Hsp90 systems, acting as both protectors and potential contributors to neurodegeneration, depending on their regulation and interaction context. By linking molecular chaperone biology to aging and translational therapeutics, this review establishes a framework for developing precision approaches that enhance proteostasis capacity, delay age-associated neurodegeneration, and promote healthy brain aging.},
}

@article {pmid41767786,
year = {2026},
author = {Stirn, YJ and Lee, WC},
title = {Estimation of Conditional Standard Errors of Measurement for MLE Scores in MST.},
journal = {Educational and psychological measurement},
volume = {},
number = {},
pages = {00131644261420391},
pmid = {41767786},
issn = {1552-3888},
abstract = {This paper proposes an information-based analytic method for calculating the conditional standard error of measurement (CSEM) in multistage testing (MST) using maximum likelihood estimation. The accuracy of the proposed method was evaluated by comparing CSEMs computed using the analytic method with those obtained from simulation across the same four MST designs. The results show that analytic and simulation-based CSEMs converge as test length increases, indicating that the proposed method provides a reliable approximation for longer tests. However, shorter tests and more complex MST designs require additional items to achieve comparable accuracy. The study also compared the proposed method with Park et al.'s analytic approach. Practical implications of the proposed method are discussed.},
}

@article {pmid41767168,
year = {2026},
author = {Bakare, AB and Lee, Y and Hong, J and Richter, CP and Kuriakose, JP},
title = {Assessing Large Language Models for Early Article Identification in Otolaryngology-Head and Neck Surgery Systematic Reviews.},
journal = {Health care science},
volume = {5},
number = {1},
pages = {19-28},
pmid = {41767168},
issn = {2771-1757},
abstract = {BACKGROUND: Assess ChatGPT and Bard's effectiveness in the initial identification of articles for Otolaryngology-Head and Neck Surgery systematic literature reviews.

METHODS: Three PRISMA-based systematic reviews (Jabbour et al. 2017, Wong et al. 2018, and Wu et al. 2021) were replicated using ChatGPTv3.5 and Bard. Outputs (author, title, publication year, and journal) were compared to the original references and cross-referenced with medical databases for authenticity and recall.

RESULTS: Several themes emerged when comparing Bard and ChatGPT across the three reviews. Bard generated more outputs and had greater recall in Wong et al.'s review, with a broader date range in Jabbour et al.'s review. In Wu et al.'s review, ChatGPT-2 had higher recall and identified more authentic outputs than Bard-2.

CONCLUSION: Large language models (LLMs) failed to fully replicate peer-reviewed methodologies, producing outputs with inaccuracies but identifying relevant, especially recent, articles missed by the references. While human-led PRISMA-based reviews remain the gold standard, refining LLMs for literature reviews shows potential.},
}

@article {pmid41766085,
year = {2026},
author = {Seco, M and Moreira, I and Oliveira, J and Moreira, S},
title = {Amyotrophic Lateral Sclerosis Caused by a Pathogenic Variant in SOD1 Gene: An Atypical Rapidly Progressive Phenotype.},
journal = {Journal of clinical neuromuscular disease},
volume = {27},
number = {3},
pages = {122-123},
doi = {10.1097/CND.0000000000000548},
pmid = {41766085},
issn = {1537-1611},
}

@article {pmid41766077,
year = {2026},
author = {Hass, RM and Reiter-Campeau, S and Laughlin, RS and Liewluck, T},
title = {Respiratory Onset Amyotrophic Lateral Sclerosis in a Patient With C9orf72 Expansion.},
journal = {Journal of clinical neuromuscular disease},
volume = {27},
number = {3},
pages = {96-98},
doi = {10.1097/CND.0000000000000556},
pmid = {41766077},
issn = {1537-1611},
mesh = {Humans ; *C9orf72 Protein/genetics ; *Amyotrophic Lateral Sclerosis/genetics/physiopathology ; *DNA Repeat Expansion/genetics ; Male ; Middle Aged ; Female ; },
abstract = {Respiratory-onset amyotrophic lateral sclerosis (ALS) is uncommon, accounting for less than 5% of all patients with ALS. Familial ALS is also uncommon, with the most common variant being related to a C9orf72 hexanucleotide repeat expansion. Respiratory-onset ALS in familial ALS is rare, with few cases discussed in the literature related to ERBB4, SOD1, and FUS variants. Here we present a case of respiratory-onset ALS related to a C9orf72 repeat expansion, expanding the spectrum of associated phenotypes associated with C9orf72 expansions and highlighting the importance of genetic testing in patients living with ALS.},
}

Humans
*C9orf72 Protein/genetics
*Amyotrophic Lateral Sclerosis/genetics/physiopathology
*DNA Repeat Expansion/genetics
Male
Middle Aged
Female

@article {pmid41766075,
year = {2026},
author = {Kuhn, C and Bromberg, M and Margolis, A and Hayes, H},
title = {Exploring Intimacy in Amyotrophic Lateral Sclerosis: A Pilot Study of Educational Support in a Multidisciplinary Clinic.},
journal = {Journal of clinical neuromuscular disease},
volume = {27},
number = {3},
pages = {82-88},
doi = {10.1097/CND.0000000000000546},
pmid = {41766075},
issn = {1537-1611},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/complications ; Pilot Projects ; Male ; Female ; Middle Aged ; Aged ; *Patient Education as Topic/methods ; Adult ; *Sexual Partners/psychology ; *Interpersonal Relations ; Surveys and Questionnaires ; },
abstract = {OBJECTIVE: This pilot study explored the feasibility and perceived usefulness of an educational intervention on intimacy delivered within a multidisciplinary ALS clinic.

METHODS: Individuals with ALS and their partners (if applicable) received the publicly available "Sexuality, Intimacy & Chronic Illness" fact sheet during routine clinic visits. A follow-up survey was conducted 4-6 weeks later to assess whether the information was informative, sufficient, and helpful. Demographic and clinical data were collected, and open-ended responses were analyzed descriptively.

RESULTS: Forty-two individuals received the fact sheet; 6 individuals and their partners (N = 12) completed follow-up surveys. Most respondents (83%) reported that ALS had impacted their intimate relationships, and 75% had discussed these changes with their partner. Half found the fact sheet informative, and 58% felt the information was sufficient. Open-ended responses revealed diverse needs, including interest in tailored content (eg, erectile dysfunction) and a desire for providers to ask permission before discussing intimacy. Caregivers described shifting roles and emotional strain, indicating that written materials alone may not fully address intimacy-related challenges.

CONCLUSIONS: Integrating discussions of intimacy into ALS care is feasible and appreciated by some patients and partners. Although written educational materials may offer a useful starting point, a more personalized, consent-based approach-potentially modeled on frameworks like Ex-PLISSIT-may better address the relational needs of individuals with ALS and their caregivers. These findings support incorporating intimacy into holistic ALS care and developing guidelines to facilitate such discussions in multidisciplinary settings.},
}

Humans
*Amyotrophic Lateral Sclerosis/psychology/complications
Pilot Projects
Male
Female
Middle Aged
Aged
*Patient Education as Topic/methods
Adult
*Sexual Partners/psychology
*Interpersonal Relations
Surveys and Questionnaires

@article {pmid41765997,
year = {2026},
author = {Wu, J and Xu, Y and Yin, T and Zhang, N and Ge, J and Fan, D and Ye, S},
title = {Voxel-mirrored homotopic connectivity in upper motor neuron-dominant amyotrophic lateral sclerosis is associated with different spread directions.},
journal = {Brain imaging and behavior},
volume = {20},
number = {2},
pages = {},
pmid = {41765997},
issn = {1931-7565},
support = {82071426//National Natural Science Foundation of China/ ; 82001350//National Natural Science Foundation of China/ ; BYSYDL2019002//Clinical Cohort Construction Program of Peking University Third Hospital/ ; YJXJ-JZ-2021-0014//Beijing E-Town Cooperation & Development Foundation/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/physiopathology/diagnostic imaging/pathology ; Male ; Female ; Middle Aged ; *Corpus Callosum/physiopathology/diagnostic imaging ; Magnetic Resonance Imaging/methods ; Aged ; Gray Matter/physiopathology/diagnostic imaging ; Neural Pathways/physiopathology/diagnostic imaging ; *Brain/physiopathology/diagnostic imaging ; Brain Mapping/methods ; Diffusion Tensor Imaging ; Adult ; Motor Neurons ; },
abstract = {By adopting the method of voxel-mirrored homotopic connectivity (VMHC), the correlation of the synchrony of spontaneous neural functional activities between symmetrical regions is determined to be mediated by the corpus callosum (CC). This study investigated differences in homotopic functional connectivity (FC) across distinct symptom spread directions in individuals with upper motor neuron-dominant amyotrophic lateral sclerosis (UMN-D ALS). The UMN-D ALS patients were categorized into two groups on the basis of the direction of symptom spread-horizontal spread (group H) and vertical spread (group V). Indices of interhemispheric functional and structural changes are derived via analyses of VMHC and probabilistic fiber tracking. The VMHC analysis of grey matter revealed that the intergroup differences in the superior frontal gyrus (SFG) were greater in group H than in groups V and HC (voxel P < 0.05, cluster P < 0.05, GRF corrected). According to CC-based VMHC analysis, group H had greater VMHC values than did group V (45 mm[3] vs. 18 mm[3] at a voxel-level threshold of P < 0.05, uncorrected). In UMN-D ALS, the results of VMHC analysis vary with different spread directions. In group H, homotopic FC significantly increased, possibly associated with early bilateral limb involvement and subsequent compensatory increases in the SFG. These results contribute to the understanding of the relationship between brain function and symptom evolution in individuals with ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/physiopathology/diagnostic imaging/pathology
Male
Female
Middle Aged
*Corpus Callosum/physiopathology/diagnostic imaging
Magnetic Resonance Imaging/methods
Aged
Gray Matter/physiopathology/diagnostic imaging
Neural Pathways/physiopathology/diagnostic imaging
*Brain/physiopathology/diagnostic imaging
Brain Mapping/methods
Diffusion Tensor Imaging
Adult
Motor Neurons

@article {pmid41765421,
year = {2026},
author = {Niidome, T and Ishida, T},
title = {[Mechanism of action and clinical trial results of a new drug for amyotrophic lateral sclerosis (ALS), Mecobalamin (Rozebalamin[®]) for intramuscular injection, 25 mg].},
journal = {Nihon yakurigaku zasshi. Folia pharmacologica Japonica},
volume = {161},
number = {2},
pages = {115-122},
doi = {10.1254/fpj.25066},
pmid = {41765421},
issn = {0015-5691},
mesh = {*Amyotrophic Lateral Sclerosis/drug therapy ; Humans ; *Vitamin B 12/administration & dosage/analogs & derivatives/therapeutic use/pharmacology ; Injections, Intramuscular ; Animals ; Clinical Trials as Topic ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive, intractable neurodegenerative disease characterized by generalized muscle atrophy and weakness, dysarthria, dysphagia, and respiratory muscle paralysis. Respiratory dysfunction due to muscle weakness is the primary cause of death; without mechanical ventilation, death typically occurs within 2 to 5 years after onset. Mecobalamin, an active form of vitamin B12, is thought to suppress homocysteine-induced neuronal cell death in ALS by acting as a coenzyme for methionine synthase, which catalyzes the conversion of homocysteine to methionine. Since the 1990s, research on neurodegenerative diseases supported by Japan's Ministry of Health, Labour and Welfare has suggested that high-dose mecobalamin may confer clinical benefits in ALS. This led to the initiation of clinical development. A Phase II/III double-blind, placebo-controlled comparative trial was conducted, but did not meet its primary endpoint. Based on these trial findings, an investigator-initiated Phase III placebo-controlled, double-blind comparative trial was conducted primarily at Tokushima University Hospital, targeting patients who developed ALS within one year before starting the trial. The trial demonstrated the efficacy of high-dose mecobalamin in slowing the decline in the Revised ALS Functional Rating Scale total score, which was the primary endpoint. Safety was also confirmed. Based on these results, mecobalamin received regulatory approval in September 2024 for the indication "slowing the progression of functional impairment in ALS." It is expected to offer a new treatment option for patients with ALS.},
}

*Amyotrophic Lateral Sclerosis/drug therapy
Humans
*Vitamin B 12/administration & dosage/analogs & derivatives/therapeutic use/pharmacology
Injections, Intramuscular
Animals
Clinical Trials as Topic

@article {pmid41765206,
year = {2026},
author = {Kotapati, C and Van Tran, LT and Cardoso, FC},
title = {Voltage-gating and neuronal signalling in neurodegeneration: From neuropathology to therapeutic opportunities in motor neuron disease.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107336},
doi = {10.1016/j.nbd.2026.107336},
pmid = {41765206},
issn = {1095-953X},
abstract = {Voltage-gated ion channels (VGICs) are central to motor neuron excitability, governing the initiation and propagation of action potentials and synaptic transmission. Disruption of their finely tuned gating properties contributes to pathology-associated hyperexcitability, a hallmark of several neurodegenerative conditions, including motor neuron disease (MND). In this review, we examine the physiological roles of voltage-gated sodium, calcium and potassium channels in motor neurons, and evaluate how mutations, altered expression, aberrant biophysics, and maladaptive signalling impair the voltage signalling processes that drive and underlie neuronal dysfunction and degeneration. We synthesise evidence linking ion channel dysfunction to altered excitability, excitotoxicity, impaired neurotransmission, motor system instability and progressive motor neuron loss in MND. We discuss current therapies that offer modest benefit and may act directly or indirectly on neuronal excitability but with limited target specificity. Motivated by the the urgent need for effective treatments for MND, we discuss emerging strategies that leverage highly selective VGIC modulators, particularly gating-modifier peptides inhibitors, to counteract hyperexcitability in MND. We further highlight that understanding how voltage-sensing and channel gating are altered in MND offers new avenues for selective targeted intervention. Together, the evidence supports VGICs as critical yet poorly explored therapeutic targets for halting motor neurodegeneration.},
}

@article {pmid41764146,
year = {2026},
author = {Ciuro, M and Sangiorgio, M and Leanza, G and Gulino, R},
title = {Neuroinflammation and Oxidative Stress in SOD1 Animal Models of ALS: A Meta-analysis Study of Their Effects on Disease Onset and Progression.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {41764146},
issn = {1559-1182},
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/pathology/metabolism ; *Oxidative Stress/physiology ; Disease Models, Animal ; *Disease Progression ; *Superoxide Dismutase-1/metabolism ; *Neuroinflammatory Diseases/pathology ; Humans ; Mice ; *Inflammation/pathology ; Male ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative disorder characterized by progressive motor neuron degeneration. Among the key mechanisms implicated in ALS pathogenesis, neuroinflammation and oxidative stress have emerged as prominent contributors to disease progression. This systematic review with meta-analysis involved 344 preclinical studies conducted on SOD1 animal models of ALS, to quantitatively evaluate the effects of treatments targeting neuroinflammation and oxidative stress on functional outcomes such as disease onset, survival, motor neuron degeneration, and locomotion. Data extraction and validation were performed using a combination of a large language model and human review. Results show that while most interventions led to reduced astrogliosis, M1 microgliosis, and oxidative stress, and increased M2 microgliosis, these effects were more strongly associated with improved survival and motor outcomes than with delayed disease onset. The analysis also revealed that treatment timing significantly influences outcomes, with interventions initiated during the late pre-onset window showing the highest efficacy. Furthermore, sex differences were noted, with male mice displaying better outcomes in progression metrics but worse in the age at onset. Overall, this meta-analysis indicates that inflammation and oxidative stress are important contributors to ALS progression in SOD1 animal models, identifies potentially critical therapeutic windows, and supports the consideration of sex-balanced and stage-specific treatment strategies at the preclinical level.},
}

Animals
*Amyotrophic Lateral Sclerosis/pathology/metabolism
*Oxidative Stress/physiology
Disease Models, Animal
*Disease Progression
*Superoxide Dismutase-1/metabolism
*Neuroinflammatory Diseases/pathology
Humans
Mice
*Inflammation/pathology
Male

@article {pmid41763528,
year = {2026},
author = {Kuznetsov, AV},
title = {Modeling the growth of cytosolic TDP-43 inclusion bodies and accumulated neurotoxicity of misfolded oligomers in neurons.},
journal = {Computer methods in biomechanics and biomedical engineering},
volume = {},
number = {},
pages = {1-28},
doi = {10.1080/10255842.2026.2618583},
pmid = {41763528},
issn = {1476-8259},
abstract = {This paper introduces a mathematical model for the growth of transactive response DNA binding protein of 43 kDa (TDP-43) inclusion bodies in neuron soma. The parameter representing the accumulated neurotoxicity caused by misfolded TDP-43 oligomers is also introduced. The model's equations enable the numerical calculation of the concentrations of TDP-43 monomers, dimers, free oligomers, and oligomers deposited in inclusion bodies. By simulating the deposition of free oligomers into inclusion bodies, the model predicts the size of TDP-43 inclusion bodies. An approximate solution to the model equations is derived for the scenario where protein degradation machinery is dysfunctional, leading to infinite half-lives for TDP-43 dimers, monomers, and both free and deposited oligomers. This solution, valid at large times, predicts that the radius of the inclusion body increases proportionally to the cube root of time, whereas the accumulated neurotoxicity increases linearly with time. To the best of the author's knowledge, this study is the first to model the relationship between the size of TDP-43 inclusion bodies and time, and the first to introduce the concept of accumulated neurotoxicity caused by misfolded TDP-43 oligomers. Sensitivity analysis of the approximate solution indicates that the inclusion body radius and accumulated neurotoxicity become independent of the kinetic constants at large timescales. Unlike the case of infinite half-lives, the numerical solution for physiologically relevant (finite) half-lives demonstrates that the long-term behavior of the inclusion body radius and accumulated neurotoxicity remains dependent on the kinetic constants, converging to distinct curves over time.},
}

@article {pmid41763443,
year = {2026},
author = {Zafarjonovna, AZ and Aysulu, E and Matlyuba, S and Rashid, H and Azamatovich, JB and Ahmadjon, A and Barno, A and Kurbanovna, AM and Ugli, MRM and Shaxodat, I and Rustam, T and Jumaniyazovna, MG and Ishankulov, A},
title = {Small extracellular vesicles as emerging biomarkers and therapeutic targets in neurodegenerative diseases.},
journal = {Clinica chimica acta; international journal of clinical chemistry},
volume = {},
number = {},
pages = {120932},
doi = {10.1016/j.cca.2026.120932},
pmid = {41763443},
issn = {1873-3492},
abstract = {Small extracellular vesicles (sEVs) have rapidly emerged as versatile mediators of intercellular communication with significant potential to transform the diagnosis and treatment of neurodegenerative diseases (NDDs). Increasing evidence shows that sEVs not only participate in the propagation of pathogenic proteins but also serve as accessible, CNS-informative carriers of molecular signatures that reflect neuronal, glial, and systemic disease processes. This dual role positions sEVs at the intersection of biomarker discovery and therapeutic innovation. In the diagnostic domain, advances in immunoaffinity capture, single-vesicle analysis, and multi-omics profiling have enabled increasingly precise characterization of neuron-, astrocyte-, and microglia-derived sEVs, revealing candidate markers for Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and related disorders. However, translation remains limited by methodological heterogeneity, a lack of large-scale validation, and the need for standardized pre-analytical and analytical pipelines aligned with the ISEV/MISEV guidelines. On the therapeutic front, native and engineered sEVs, particularly those derived from mesenchymal and neural stem cells, demonstrate promising neuroprotective effects, including the modulation of neuroinflammation; the enhancement of synaptic resilience; and the delivery of antioxidant, anti-amyloid, or gene-modifying cargo across the blood-brain barrier. Scalable GMP manufacturing, cargo-loading strategies, targeting specificity, and long-term safety remain key challenges for clinical translation. This narrative review synthesizes current advances in sEV-based biomarkers and therapeutics, outlines technological and regulatory barriers, and proposes a translational roadmap spanning mechanistic discovery, platform standardization, and integration into precision-medicine frameworks. Collectively, emerging data position sEVs as powerful tools capable of reshaping the diagnostic and therapeutic landscape of NDDs, provided that coordinated multidisciplinary efforts address the remaining gaps in validation, scalability, and regulatory readiness.},
}

@article {pmid41763422,
year = {2026},
author = {Li, Y and Liu, S and Cao, L and Zhu, M and Lin, S and Wang, X and Qiu, Z and Teng, Y},
title = {Ginsenoside compound K inhibited the gelation of GGGGCC repeats and regulated co-aggregation with arginine-rich poly-dipeptides in C9orf72-related ALS.},
journal = {International journal of biological macromolecules},
volume = {351},
number = {},
pages = {151138},
doi = {10.1016/j.ijbiomac.2026.151138},
pmid = {41763422},
issn = {1879-0003},
abstract = {GGGGCC repeat expansion in C9orf72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). It produces toxic RNA repeats and poly-dipeptides, leading to abnormal phase separation and deposition in nerve cells. In particular, repeat RNAs form gels that induce cellular toxicity. Thus, they are potential therapeutic targets. Ginsenoside compound K (CK) is the major metabolite of Panax ginseng, a traditional Chinese medicine commonly used for the treatment of neurodegenerative diseases. In this study, CK significantly inhibited the gelation of GGGGCC repeats both in vitro and in vivo. Moreover, it reduced the co-aggregation of RNA and arginine-rich poly-dipeptides via electrostatic interactions. Further investigation suggested that CK preferentially interacts with G-quadruplex monomers formed by GGGGCC repeats rather than with complex multimers, thereby inhibiting the formation of toxic RNA foci. These results elucidate the mechanism of action of CK in C9orf72-related ALS/FTD. Thus, this study provides new avenues for the potential application of ginsenoside in the treatment of neurodegeneration.},
}

@article {pmid41763275,
year = {2026},
author = {Shi, B and Liu, M and Wang, Y},
title = {ATCRN: Attention-guided Temporal Convolutional Remix Network for P300 speller.},
journal = {Journal of neuroscience methods},
volume = {430},
number = {},
pages = {110727},
doi = {10.1016/j.jneumeth.2026.110727},
pmid = {41763275},
issn = {1872-678X},
abstract = {BACKGROUND: The P300 speller is a prominent brain-computer interface (BCI) that facilitates communication by detecting P300 event-related potentials. However, its performance is substantially constrained by the low signal-to-noise ratio of EEG signals and the inherent temporal variability of the P300 response.

NEW METHOD: We propose the Attention-guided Temporal Convolutional Remix Network (ATCRN), an end-to-end model that synergistically integrates a novel Temporal Convolutional Remix Network (TCRN) with a dual-attention framework. The TCRN employs multi-level skip connections to enable dynamic, cross-hierarchical fusion of local and global temporal features, addressing the variable latency of P300. Externally, the Convolutional Block Attention Module (CBAM) suppresses noise in spatial and channel dimensions. Internally, Efficient Channel Attention (ECA) modules within TCRN block perform dynamic channel recalibration.

RESULTS: On BCI Competition III Dataset II, ATCRN achieved character recognition rates of 99% and 98% for two subjects at the 15th repetition, and yielded superior information transfer rates. Evaluation across eight ALS patients showed robust P300 detection (average AUC-ROC 0.882).

ATCRN outperforms both established CNN/TCN benchmarks and recent Transformer-based models across two public datasets, achieving state-of-the-art results in P300 detection and character spelling.

CONCLUSION: The proposed ATCRN provides a novel, robust, and effective decoding framework for the P300 speller. The integration of TCRN for temporal feature fusion and the dual-attention mechanism for feature refinement offers a practical solution for advancing BCI applications.},
}

@article {pmid41762823,
year = {2026},
author = {Nissinen, P and Silén-Lipponen, M and Kähkönen, O and Saaranen, T},
title = {Nursing students' learning experiences, outcomes, and methods in distance education: An integrative literature review.},
journal = {Nurse education today},
volume = {162},
number = {},
pages = {107051},
doi = {10.1016/j.nedt.2026.107051},
pmid = {41762823},
issn = {1532-2793},
abstract = {BACKGROUND: The transformation of nursing education has emphasized the role of distance education as a permanent component. Nursing students' learning experiences and outcomes in this format show considerable variation and raise questions about the most effective distance learning methods.

AIMS: The aim of this integrative review was to explore nursing students' experiences with distance learning, identify the learning outcomes it produces, and examine the distance learning methods used in nursing education.

DESIGN: Integrative literature review.

METHODS: A systematic literature search was conducted in the CINAHL (EBSCO, PubMed/Medline, Education database (ProQuest), Scopus and ERIC (EBSCO) databases, including peer-reviewed studies published in English between 2018 and 2024. The review followed the PRISMA 2020 guidelines. Quality appraisal was performed using Hawker et al.'s evaluation tool. Data was analyzed using inductive content analysis.

RESULTS: A total of 43 studies were included in the review. Five main themes were identified describing students' experiences: the accessibility of digital learning platforms, the quality and structure of learning materials, the acquisition of practical and clinical skills, social interaction and peer support, motivation, self-regulation, and emotional well-being. Learning outcomes were categorized into cognitive, psychomotor, and affective domains. The most common learning methods included synchronous, asynchronous, and blended approaches, with blended learning showing particularly positive results.

CONCLUSION: Distance education can support nursing students' learning when it is well-structured and combines pedagogical planning with interactive and practical elements. Not all competencies, particularly clinical skills, can be taught remotely. The learning experience is shaped by individual abilities, guidance, and technical conditions, and distance education may not suit all students equally well. Effective methods, especially blended learning, support engagement and learning when aligned with student needs and pedagogical goals.},
}

@article {pmid41762671,
year = {2026},
author = {Gaur, N and Angerer, C and Gunes, ZI and Ancau, M and Wang, M and Riemenschneider, H and Hurler, CA and Mungwa, S and Lüningschrör, P and Zhiti, A and Steinbach, R and Briese, M and Srivastava, M and Plaas, M and Hermann, A and Sendtner, M and Jäkel, S and Edbauer, D and Herms, J and Liebscher, S and Grosskreutz, J and Brill, MS},
title = {Constitutive neuronal expression and disease-associated upregulation of chitinases in amyotrophic lateral sclerosis.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awag083},
pmid = {41762671},
issn = {1460-2156},
abstract = {Chitinases are hydrolytic enzymes responsible for degrading chitin and have been evolutionarily conserved across various species. Although their signaling pathways are not fully understood, the chitinases are considered active immunomodulators across several cell types. Specific isoforms, including Chitotriosidase-1 (CHIT1), Chitinase-3-like protein 1 (CHI3L1), and human-specific Chitinase-3-like protein 2 (CHI3L2), have emerged as markers of inflammation across the neurodegenerative spectrum, including amyotrophic lateral sclerosis (ALS). ALS is a fatal neuromuscular condition, and therapeutic development has been severely hindered by phenotypic heterogeneity and an incomplete understanding of etiology. Although several overlapping disease mechanisms can contribute to neuronal death, inflammation can exacerbate pathology. Prior studies have reported that CHIT1, CHI3L1, and CHI3L2 levels are elevated in the cerebrospinal fluid (CSF) of ALS patients and associated with disease aggressiveness. Nevertheless, several open questions critical to our understanding of the chitinases' role in ALS disease burden remain: namely, 1) which cell types in the central nervous system (CNS) are chitinase sources under physiological conditions, 2) which of these display chitinase upregulation in ALS, and 3) what is the diagnostic utility of the chitinases relative to established biomarkers. Here, we utilize pre-clinical models and post-mortem human tissue to demonstrate at both the transcriptomic and protein level that neurons are a primary source of chitinases; furthermore, neuronal chitinase expression is conserved across species. Under physiological conditions, CHI3L1 is more abundant and widely expressed across various cell types, whereas CHIT1 is predominantly expressed in neurons. Additionally, utilizing symptomatic mice from three familial ALS models, we demonstrate isoform-specific expression profiles, with astroglial and microglial upregulation of CHI3L1, and neuronal and microglial upregulation of CHIT1. Differing expression dynamics and diagnostic utility were also noted in our clinical cohort: CSF CHIT1 and CHI3L2 levels had more discriminatory power when distinguishing between ALS vs. non-ALS controls, while CHI3L1 was more closely associated with inflammation and aging across the neurodegenerative spectrum. Although the chitinases did not diagnostically outperform the neurofilament proteins as biomarkers, we propose that appreciating their expression patterns can aid in optimizing biomarker-guided trial design. Taken together, we demonstrate that chitinase upregulation in ALS is evident in various CNS cell types and that its neuronal expression may provide new insights into its role in disease activity.},
}

@article {pmid41762620,
year = {2026},
author = {Ing, L and Griffiths, AW and Mayberry, E and Ali, Y and Blackburn, D and McDermott, C},
title = {Patient and caregiver attitudes to cognitive and behavioral testing in Amyotrophic Lateral Sclerosis.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/17582024.2026.2637424},
pmid = {41762620},
issn = {1758-2032},
abstract = {BACKGROUND: Cognitive and behavioral changes affect up to 50% of people with Amyotrophic Lateral Sclerosis (ALS) and are associated with worse outcomes, yet remain under-recognized in clinical care. Understanding patient and caregiver perspectives is important for engagement with cognitive screening.

METHODS: Semi-structured interviews were conducted with 10 patients with ALS and 9 caregivers, analyzed using reflexive thematic analysis. Participants were recruited via a multidisciplinary ALS clinic and the Motor Neurone Disease Association UK.

RESULTS: Engagement with testing was shaped by emotional readiness, personal values, relational dynamics, practical barriers, and perceived value. Views ranged from seeing testing as an opportunity for preparedness and autonomy, to concerns it could undermine identity or add distress. Caregivers often valued testing to support planning but faced challenges balancing advocacy with respect for patient autonomy. Limited awareness of cognitive symptoms in ALS and unclear communication from clinicians reduced perceived relevance. Testing was most meaningful when tailored to personal priorities, introduced sensitively, and linked to actionable outcomes.

CONCLUSION: Cognitive screening in ALS requires a flexible, patient-centered approach that considers emotional readiness, relational contexts, and clear communication. Tailoring discussions and delivery to patient and caregiver needs may enhance acceptance and integration of cognitive assessment into holistic ALS care.},
}

@article {pmid41762049,
year = {2026},
author = {Zhang, Y and Chen, B and Lin, Y and Kang, D and Zhao, T},
title = {Advances and Challenges in the Use of Spinal Cord Organoids in ALS.},
journal = {Journal of integrative neuroscience},
volume = {25},
number = {2},
pages = {44709},
doi = {10.31083/JIN44709},
pmid = {41762049},
issn = {0219-6352},
support = {82301543//National Natural Science Foundation of China/ ; 2021QNA025//Youth Scientific Research Project of Fujian Provincial Health Commission/ ; 2021Y2001//Technology Platform Construction Project of Fujian Province/ ; 2020Y2003//Technology Platform Construction Project of Fujian Province/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/pathology/therapy ; *Organoids/pathology ; Humans ; *Spinal Cord/pathology ; Animals ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease. No effective treatments have yet been found for ALS, primarily because the molecular mechanisms that underlie its pathogenesis are unknown. Although animal models are suitable for ALS research, species differences between these models and human spinal cord organs make it difficult to accurately predict the progression of disease in humans. Therefore, the development of more suitable models is urgently needed. Human stem cells have unlimited development potential and can be used to make three-dimensional organoid structures that mimic the architecture and function of actual organs. Organoid models can be used to overcome some of the species differences and accelerate experimental research, leading to the development of practical applications for the treatment of ALS. This article discusses the pathological mechanisms and cell types involved in ALS, as well as the genes associated with this disease. We also discuss the possible applications of spinal cord organoids (SCOs) in ALS research, such as the modeling of disease characteristics, study of pathological mechanisms, and drug screening. Finally, the prospects for SCOs in ALS treatment are highlighted, while acknowledging the need for further development of relevant technologies.},
}

*Amyotrophic Lateral Sclerosis/pathology/therapy
*Organoids/pathology
Humans
*Spinal Cord/pathology
Animals

@article {pmid41760992,
year = {2026},
author = {Hollin, IL and Ilieva, H and Pasinelli, P and Chisholm, L and Heiman-Patterson, T},
title = {Preferences for Healthcare Delivery in Amyotrophic Lateral Sclerosis (ALS): A Survey of Patients and Caregivers in the United States.},
journal = {The patient},
volume = {},
number = {},
pages = {},
pmid = {41760992},
issn = {1178-1661},
abstract = {BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and fatal neurological disease that leads to death within 2-5 years of diagnosis for more than 80% of people living with ALS (PLWALS). The American Academy of Neurology (AAN) developed practice parameters-general principles to guide clinicians in managing ALS-encouraging multidisciplinary care (MDC) but does not recommend specific healthcare delivery models. Three healthcare delivery models have evolved: a traditional model, a triage model, and a non-triage model. This study aims to describe preferences for and satisfaction with various models, among PLWALS and their caregivers (CALS), along with their perceptions of how their care aligns with AAN guidelines.

METHODS: A cross-sectional observational study utilizing a web-based survey was distributed via email to PLWALS and CALS. Three multi-assessment questionnaires were developed and tailored for PLWALS, CALS, and former CALS. Best-worst scaling (object case) data were analyzed using a best-minus-worst approach and descriptive statistics were calculated from means, t-tests and chi-square.

RESULTS: The combined sample included 378 respondents: 254 PLWALS (67.20%) and 124 CALS (32.80%; composed of 79 current caregivers [20.90%] and 45 former caregivers [11.90%]). The mean respondent age was 61.09 years (SD 11.1). The majority of the sample was white (92.86%), insured by Medicare (61.11%), and married/partnered (79.10%). Respondents preferred a non-triage model the most and a traditional model the least; 88.20% (CI: 84.92-91.49) were extremely likely to choose a non-triage model if given the choice and 83.12% (CI: 79.29-86.92) of respondents ranked non-triage as most preferred. A traditional model was ranked as the least preferred model in 75.28% (CI: 70.78-79.78) of respondents. The most important factors driving respondent preferences were ALS expertise and team-based care. Overall, respondents are satisfied with their care teams. PLWALS utilizing non-triage MDC models reported more adherence to quality care measures compared with those utilizing triage and traditional models.

DISCUSSION: Respondent preference for non-triage models is consistent with the importance they place on the features of non-triage models. However, these findings should be understood in the context of our sample in which a large majority of respondents were receiving care via a non-triage model. To ensure ALS care delivery is patient-centered, practice parameters that aim to guide clinicians in managing ALS should provide more guidance to MDCs to deliver care aligned with patient preferences and values. Efforts should focus on sustainable financial models that can better facilitate non-triage models of care.},
}

@article {pmid41760955,
year = {2026},
author = {D'Amico, A and Cucunato, R and Schirò, G and Salemi, G and Ragonese, P and La Bella, V and Aridon, P and D'Amelio, M},
title = {KIF5A and ALS: a clinical and genetic description of a case series and review of literature.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {3},
pages = {},
pmid = {41760955},
issn = {1590-3478},
abstract = {Approximately 10% of ALS (amyotrophic lateral sclerosis) cases show a family history, and the remaining 90% are sporadic. In 2018, through genome sequencing using two independent approaches, KIF5A was described as a novel ALS-associated gene. To describe clinical and genetic characteristics of a series of patients with motor neuron disease (MND), diagnosed at University Hospital of Palermo, carrying KIF5A variants. During 2019–2023, two hundred twenty-four patients with MND and healthy subjects with familial history of MND, underwent next-generation sequencing (NGS) for molecular analysis, including genetic testing for C9orf72 hexanucleotide-repeat expansion. The most mutated ALS genes, including KIF5A, were included in a NGS panel. Of the entire tested population, eight patients (including a brother and a sister) were found to carry KIF5A variants. Four patients had familial ALS, the other four were sporadic. Six patients were females (75%). Mean age at ALS onset was 59 years (33–75). Patients were evaluated according to the ALSFRS-revisited during follow-up visits. According to disease progression rate, five patients were defined as ∆FS ≤ 0.5 (slow-progressors), the remaining three patients showed a ∆FS > 1 (fast-progressors). Of the seven KIF5A variants, three are not already described in literature (respectively c.170 C > T, p.Thr57Met; c.2920T > G, p.Ser974Ala and c.2732 A > C, p.Lys911Thr). Two patients showed the association of variations in KIF5A with variations or mutations in other ALS genes, one of them carried a pathogenic variant of FUS (P525L). This study demonstrates phenotypic variability related to mutations in different regions of the same gene resulting in a susceptibility for the disease spectrum with different characteristics.},
}

@article {pmid41760732,
year = {2026},
author = {Sinderewicz, E and Dąbkowska, M and Sarnowska, A and Staszkiewicz-Chodor, J and Mystkowska, D and Holak, P and Drozd, I and Chodkowska-Michalowska, M and Rytel, M and Paczkowska, E and Mycko, MP and Machalinski, B and Jezierska-Wozniak, K},
title = {Safety and biodistribution of intrathecal administration of mesenchymal stem cells (MSCs) and neurotrophin-releasing nanoparticles in a porcine CSF-guided delivery model for amyotrophic lateral sclerosis (ALS) drug discovery.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-40196-0},
pmid = {41760732},
issn = {2045-2322},
support = {No: 2020/ABM/01/00014-00//Medical Research Agency, Poland/ ; No: 2020/ABM/01/00014-00//Medical Research Agency, Poland/ ; No: 2020/ABM/01/00014-00//Medical Research Agency, Poland/ ; No: 2020/ABM/01/00014-00//Medical Research Agency, Poland/ ; No: 2020/ABM/01/00014-00//Medical Research Agency, Poland/ ; No: 2020/ABM/01/00014-00//Medical Research Agency, Poland/ ; No: 2020/ABM/01/00014-00//Medical Research Agency, Poland/ ; No: 2020/ABM/01/00014-00//Medical Research Agency, Poland/ ; No: 2020/ABM/01/00014-00//Medical Research Agency, Poland/ ; No: 2020/ABM/01/00014-00//Medical Research Agency, Poland/ ; No: 2020/ABM/01/00014-00//Medical Research Agency, Poland/ ; No: 2020/ABM/01/00014-00//Medical Research Agency, Poland/ ; No: 2020/ABM/01/00014-00//Medical Research Agency, Poland/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative disorder that complicates the identification of effective therapeutic targets. The potential of stem cells and neurotrophins as promising candidates has become increasingly evident, owing to their neuroprotective and anti-inflammatory properties. In this study, a preclinical evaluation of the safety and biodistribution of mesenchymal stromal/stem cells (MSCs) combined with neurotrophin-releasing polyelectrolyte nanoparticles (NTs) was conducted in a porcine intrathecal delivery model relevant to ALS therapy development. Four groups of male pigs were administered saline with NTs, adipose-derived stem cells (ASCs) with NTs, Wharton's jelly-derived MSCs (WJ-MSCs) with NTs, or spinal puncture only. The safety of the treatment was assessed using magnetic resonance imaging (MRI), haematological and biochemical analyses, cerebrospinal fluid profiling, and histology. No adverse effects or significant systemic alterations were observed. It is noteworthy that C-reactive protein levels diminished following NT and NT-MSC administration, suggesting a systemic anti-inflammatory effect. The migration of MSCs was facilitated by cerebrospinal fluid, leading to their accumulation around the spinal cord and brain parenchyma. The present findings demonstrate short-term safety and biodistribution patterns following intrathecal administration of MSCs combined with neurotrophin-releasing nanoparticles in a large-animal model. These preliminary observations provide a pilot framework for future efficacy studies in disease-specific ALS models. This work establishes a translational platform for the development of future ALS therapies, with subsequent studies focused on efficacy testing in disease-specific models that more accurately reflect the slow, heterogeneous, multisystem nature of human ALS.},
}

@article {pmid41759589,
year = {2026},
author = {Cooper, M and Singh, S and Ferrer, E and Turner, S and Timko, CA},
title = {Calculating developmental weight suppression in practice: A commentary demonstrating the use and misuse of Singh and colleagues' new approach.},
journal = {Appetite},
volume = {222},
number = {},
pages = {108513},
doi = {10.1016/j.appet.2026.108513},
pmid = {41759589},
issn = {1095-8304},
abstract = {Eating disorders (ED) typically onset during youth, a critical period of growth and development. Maintenance of appropriate body weight is a criterion in multiple ED diagnoses and informs weight restoration. Data suggest that weight suppression (WS), the difference between an individual's highest historical and current weights, may be linked to ED severity and prognosis. Singh et al. (2021) formulated a developmentally-adjusted measure of WS using BMI z-scores to account for developmental growth during adolescence. Studies since have established both the face and incremental validity of developmental WS with respect to eating concerns, binge eating behavior, and abnormal endocrine and metabolic markers of ED, suggesting its benefit over traditional estimates of WS. Unfortunately, however, many studies have misapplied Singh et al.'s method by using z-scores based on highest premorbid weight, rather than using highest premorbid BMI z-score. This error can lead to underestimation of developmental WS. In this commentary, we present several case examples to demonstrate the importance of using growth chart data to identify the highest BMI z-score for the purpose of developmental WS calculation, as opposed to self-report highest past weight and height. We discuss how this procedure influences target weight calculation, the need for weight restoration in treatment, and diagnostic and clinical care considerations.},
}

@article {pmid41759446,
year = {2026},
author = {Salmon, PM and King, B and Hall, D and McLean, S and Thompson, J and Cooke, N and Salas, E and Loft, S and Read, GJM},
title = {The big five model of teamwork and human autonomy teams: a scoping review.},
journal = {Applied ergonomics},
volume = {135},
number = {},
pages = {104761},
doi = {10.1016/j.apergo.2026.104761},
pmid = {41759446},
issn = {1872-9126},
abstract = {Teams play a critical role in society and represent a key area for Human Factors and Ergonomics. Salas et al.'s Big Five model is widely cited; however, the increasing use of Human-Autonomy Teams (HATs) has fuelled debate over its continued relevance. It is important to reflect on how the Big five model has been applied, in what contexts, and whether applications to contemporary teams are emerging. This article presents the findings from a scoping review undertaken to identify and synthesise the peer reviewed literature describing applications of the Big Five model. Articles were deemed eligible for inclusion if they were published in the peer reviewed literature and described an application of the Big Five model to study teamwork. 38 articles were included in the review and no applications of the Big Five model to study HATs were identified. Over half of the studies were undertaken in healthcare and a range of assessment methods have been used (e.g., questionnaires, surveys, interviews, observer-rating scales, communication transcript analysis). Just under a third of included studies evaluated all model components (i.e., the five processes and three coordinating mechanisms) and few considered the relationships between model components or between model components and team effectiveness. Research is required to explore the validity of the Big Five model for HATs, to gather evidence for the relationship between model components and team effectiveness, and to develop more precise Big five-based measures.},
}

@article {pmid41759417,
year = {2026},
author = {Zhang, M and Zhang, Y and Pu, Y and Bai, X},
title = {Ultra-high-dose methylcobalamin demonstrates safety in advanced ALS, but intramuscular administration poses practical burdens and its selected study cohort limits generalizability.},
journal = {Journal of the neurological sciences},
volume = {483},
number = {},
pages = {125838},
doi = {10.1016/j.jns.2026.125838},
pmid = {41759417},
issn = {1878-5883},
}

@article {pmid41757350,
year = {2026},
author = {Lee, JAK and Moutin, C and Granger, S and Roome, K and Shaw, A and Allen, SP and Ferraiuolo, L and Shaw, PJ and Mortiboys, H},
title = {C9orf72-ALS mutation drives basal mitophagy impairments in iNeurons.},
journal = {Frontiers in cellular neuroscience},
volume = {20},
number = {},
pages = {1731669},
pmid = {41757350},
issn = {1662-5102},
abstract = {INTRODUCTION: ALS is a neurodegenerative disorder characterized by progressive upper and lower motor neuron loss. A GGGGCC hexanucleotide repeat expansion (HRE) in the C9orf72 gene is the most common mutation found in populations of European descent. Mitochondrial dysfunction has been observed in C9orf72-ALS patients and models of the disease, however, reports on mitochondrial clearance via mitophagy in C9orf72-ALS are limited.

RESULTS: iNeurons from C9orf72-ALS patients displayed reduced mitochondrial membrane potential and reduced basal mitophagy, due to reductions in autophagosome production and reduced ULK1 recruitment to mitochondria. No consistent changes to PINK1/Parkin or BNIP3 mitophagy pathways were observed.

CONCLUSION: Our data show that certain aspects of mitochondrial function is impaired in C9orf72-ALS patient iNeurons. An in-depth characterization of mitophagy suggests that a deficit in autophagosome production is responsible and provides further evidence that toxic gain-of-function mechanisms in C9orf72-ALS are responsible for autophagy deficits.},
}

@article {pmid41757182,
year = {2026},
author = {Puerta, R and Garcia-Gonzalez, P and de Rojas, I and Capdevila-Bayo, M and Olive, C and Munoz-Morales, A and Bayon-Bujan, P and Valenzuela, A and Yang, C and Timsina, J and Liu, M and Chakkarai, S and Sotolongo-Grau, O and Calm, B and Miguel, A and Solivar, A and Montrreal, L and Martinez, M and Khan, A and Zhao, F and Tantinya, N and Rosende-Roca, M and Alegret, M and Moreno-Grau, S and Fernandez, MV and Marquie, M and Valero, S and Cavazos, JE and Sanz, P and Montalban, X and Tarraga, L and Smets, B and Boada, M and Seshadri, S and Sargurupremraj, M and Cruchaga, C and Cano, A and Cabrera-Socorro, A and Ruiz, A},
title = {Human CSF proteogenomics links genetic variation to neurodegenerative disease proteins.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.02.12.26345733},
pmid = {41757182},
abstract = {The cerebrospinal fluid (CSF) proteome offers a direct readout of central nervous system (CNS) biology but its genetic architecture remains incompletely defined. We conducted the largest single-site CSF genome-wide association study (GWAS) to date, analysing 7,092 SomaScan proteins in 1,259 individuals. Using a covariate-adjusted model including proteomic PCs and disease status, we identified 1,971 genome-wide significant pQTLs (954 cis, 971 trans), 1,409 of which replicated in an independent CSF dataset. We discovered 264 previously unreported loci, replicated 511 associations, refined 80 known loci, and 265 proxy-based associations. Using a previously published reproducibility framework, we show that robust discovery concentrates in reliable measurements, underscoring the importance of rigorous quality control. Enrichment analyses revealed immune/complement and extracellular matrix biology. Mendelian randomization prioritised causal proteins: PILRA, TREM2, IL34, CR2, SHARPIN and ERBB1 (Alzheimer's disease); BST1 and GPNMB (Parkinson's disease); STX6 (Creutzfeldt Jacobs disease); and ATXN3 and B4GALNT1 (Amyotrophic lateral sclerosis), providing a scalable framework for orthogonal target validation in neurodegeneration.},
}

@article {pmid41756973,
year = {2026},
author = {Plessis-Belair, J and Sher, RB},
title = {Neuronal Cell-Cycle Re-entry Defines Divergent Outcomes Through Replication-Dependent DNA Damage in ALS.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.02.13.705790},
pmid = {41756973},
issn = {2692-8205},
abstract = {Cell-cycle dysregulation has emerged as a shared mechanism of neuronal loss across neurodegenerative diseases (NDDs), including amyotrophic lateral sclerosis (ALS), Alzheimer's disease, and Parkinson's disease. In post-mitotic neurons, aberrant reactivation of cell-cycle signaling precedes degeneration, yet the upstream triggers and functional consequences of this process remain poorly defined. Nucleocytoplasmic transport (NCT) dysfunction, a hallmark of ALS and related disorders, disrupts the spatial distribution of key regulatory proteins and may contribute to maladaptive cell-cycle activation. Our recent evidence suggests that impaired nuclear import may initiate, rather than merely accompany, neuronal cell-cycle re-entry. Here, we show that cell-cycle activation in motor neurons distinguishes molecular subtypes and outcomes in ALS. We analyzed the AnswerALS transcriptomic cohort and identified a patient cluster characterized by robust upregulation of cyclins B and D. Clusters with lower levels of cell-cycle gene expression exhibited accelerated ALSFRS-R decline, whereas the highest cyclin-expressing cluster demonstrated comparatively improved functional trajectories over time. To test whether NCT disruption can mechanistically drive aberrant cell-cycle activation, we pharmacologically inhibited importin-β in human iPSC-derived spinal motor neurons. NCT disruption induced widespread proteomic mislocalization, including TDP-43 pathology, and triggered a transient wave of cell-cycle activity preceding neuronal death. Mechanistically, we identified DNA-replication initiation as a pathological event driving degeneration and demonstrated that selective inhibition of G1/S-associated CDK4/6 activity confers neuroprotection. Together, these findings link impaired nuclear import to maladaptive cell-cycle reactivation in neurons and highlight stage-specific engagement of the cell-cycle machinery as a determinant of neuronal vulnerability in ALS.},
}

@article {pmid41756852,
year = {2026},
author = {Malik, T and Jones, S and Ma, O and Mohan, S and Burger, RM and Babcock, DT},
title = {Autophagy induction mitigates FUS aggregate formation and early synaptic dysfunction at the NMJ in the FUS-ALS model.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.02.19.706635},
pmid = {41756852},
issn = {2692-8205},
abstract = {Mutations in Fused in Sarcoma (FUS), a RNA binding protein, cause Amyotrophic Lateral Sclerosis (ALS). ALS is an aggressive neurodegenerative disease resulting in motor neuron degeneration. Defects in synaptic integrity precede neuronal loss in ALS, but the mechanisms responsible for these early synaptic defects are unclear. To investigate early synaptic defects associated with ALS, we expressed an ALS-linked variant of human FUS in adult motor neurons and assessed synaptic pathology at the neuromuscular junction (NMJ). Here we highlight the accumulation of FUS-positive aggregates at synaptic terminals and subsequent reduction in microtubule stability. We show that inducing autophagy via expression of Rab1 or Fragile-X Mental Retardation Protein 1 (FMR1), or treatment with Rapamycin reduces aggregate formation and restores synaptic structure and function. These findings reveal the utility of inducing autophagy to address early synaptic dysfunction in an ALS model and demonstrate a potential therapeutic target to preventing later stages of disease progression.},
}

@article {pmid41756850,
year = {2026},
author = {Wake, N and Alcalde, J and Jutzi, D and Bajaj, A and Kour, S and Barai, M and Weng, SL and Cummings, S and Zheng, T and Anderson, EN and Wang, SH and Puterbaugh, R and Bosco, DA and Schuster, BS and Mittal, J and Pandey, UB and Ruepp, MD and Fawzi, NL},
title = {Breaking β-sheets in FUS prion-like domain preserves phase separation and function but prevents aggregation and toxicity.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.02.17.706410},
pmid = {41756850},
issn = {2692-8205},
abstract = {UNLABELLED: The RNA-binding protein Fused in Sarcoma (FUS) undergoes phase separation associated with RNA processing. However, the prion-like low complexity (LC) domain of FUS forms solid-like aggregates in neurodegenerative diseases. Whether the formation of β-sheet structure associated with pathology is also physiologically/functionally relevant is debated. Similarly, if mislocalization alone or concomitant aggregation is responsible for FUS gain-of-function toxicity remains to be probed. Here, we introduce β-sheet breaking proline residues into FUS LC with the goal of preventing cross-β-driven aggregation without disrupting essential functions and phase separation. β-sheet-deficient FUS variants maintain native-like global motions, disorder, and phase separation, but no longer show a liquid-to-solid transition (LST). Biochemical partitioning, cellular localization, and auto- and cross-regulatory functions of FUS all remain essentially unchanged. Conversely, FUS-induced neurodegeneration in several Drosophila models is drastically reduced. These findings suggest a strategy for mitigating disease-related toxicity through backbone structure modulation to prevent prion-like domain protein aggregation.

SUMMARY: The RNA-binding protein Fused in Sarcoma (FUS) undergoes phase separation as part of its physiological function but can aberrantly aggregate into solid-like assemblies in amyotrophic lateral sclerosis and frontotemporal dementia. To dissect the role of β-sheets in both function and pathological transition, we engineered β-sheet-preventing FUS variants via targeted proline residue insertions in the prion-like disordered region. These variants retained native structure, motions, and phase behavior yet showed dramatically reduced aggregation, both as an isolated prion-like domain and in full-length FUS. Crucially, these variants maintained a panel of FUS cellular functions that depend on FUS condensation but prevented FUS toxicity in fly models of neurodegeneration. Our findings implicate β-sheets as key drivers of FUS condensate maturation and neuronal toxicity, highlighting β-sheet modulation as a therapeutic strategy against FUS-related neurodegeneration.

HIGHLIGHTS: Targeted proline additions disrupt β-sheet formation in FUS without altering native conformations, dynamics, or phase separation behaviorβ-sheet-deficient FUS variants prevent aggregation and liquid-to-solid transitions while retaining key biological functions In vivo models reveal attenuated toxicity of β-sheet-deficient FUS in Drosophila β-sheets are identified as central drivers of condensate maturation and neuronal death, offering a therapeutic entry point for modulating prion-like domain pathology.},
}

@article {pmid41756461,
year = {2026},
author = {Petriti, B and Subramanian, S and Williams, P and Chau, KY and Licznerski, P and Lascaratos, G and Aguilar-Munoa, S and Kamal, D and Bae, H and Alavian, K and Garway-Heath, D and Jonas, E},
title = {Reversing Mitochondrial Dysfunction in Optineurin E50K Glaucoma: A Metabolic Approach to Neuroprotection.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-8380062/v1},
pmid = {41756461},
issn = {2693-5015},
abstract = {Mutations in optineurin (OPTN) are linked to neurodegenerative diseases such as normal tension glaucoma (NTG) and amyotrophic lateral sclerosis. The E50K-OPTN mutation is the most common genetic cause of NTG, where it disrupts mitophagy and leads to the accumulation of dysfunctional mitochondria. To understand how cellular metabolism is altered in these persistent mitochondria, and whether any pathological state can be reversed, we investigated NTG-patient-derived fibroblasts carrying the E50K-OPTN mutation. We identified a form of mitochondrial leak metabolism driven by elevated levels of the ATP synthase c-subunit leak channel (ACLC). These cells exhibit reversed F1FO ATP synthase activity, increased mitochondrial proton leak, and fragmented mitochondria, resulting in inefficient oxidative phosphorylation and a shift toward aerobic glycolysis and high protein synthesis rate. The ratio of ATP synthase c-subunit to β-subunit was markedly elevated, suggesting open ACLC pores. Treatment with dexpramipexole normalized ATP synthase function and cellular metabolism, promoted ATP synthesis rather than hydrolysis and reduced protein synthesis rates. Dexpramipexole reduced p62 levels in E50K fibroblasts, consistent with a reduced mitophagic burden from decreased accumulation of damaged mitochondrial cargo. These findings identify ACLC-mediated leak as a central driver of metabolic dysfunction in E50K-OPTN glaucoma and suggest ACLC closure as a viable therapeutic strategy.},
}

@article {pmid41754783,
year = {2026},
author = {González-Rivera, ML and Juárez-Vázquez, MDC and Melecio-Hernández, AA and Casique-Aguirre, D and López-González, GJ and Ramírez-Martínez, RM and Ayala-Torres, A and Quesada-Mendiola, Y and Zapata-Morales, JR and Alonso-Castro, AJ},
title = {Antidepressant-Like Effects of n-Butylidenephthalide Using In Vivo and In Silico Approaches.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {19},
number = {2},
pages = {},
pmid = {41754783},
issn = {1424-8247},
support = {CBF2023-2024-1888//Secretariat of Science, Humanities, Technology, and Innovation/ ; },
abstract = {Background: The plant-derived compound n-butylidenephthalide (BP) is an isobenzofuranone that has shown neuropharmacological effects on preclinical models of Parkinson's, Alzheimer's, and amyotrophic lateral sclerosis. Methods: This study evaluated the anti-inflammatory, antinociceptive, anxiolytic-like, hypnotic, anticonvulsant, and antidepressant-like effects of BP (50-200 mg/kg p.o.) using Balb/c mice in acute assays. This study also evaluated the antidepressant-like effects of BP in a mouse model of reserpine-induced depression-like behavior for 20 days. Inhibitors involved in the molecular process of depression and in silico studies were used to evaluate a possible mechanism of action for the antidepressant-like effects of BP. Results: BP induced low anti-inflammatory effects, showed low anticonvulsant effects, and lacked hypnotic effects or motor impairment in acute assays. The antidepressant-like effects of BP (100-200 mg/kg p.o.) were comparable to amitriptyline (25 mg/kg p.o.) in acute assays. The participation of serotonergic and adrenergic systems is involved in the acute antidepressant-like effects of BP. In the reserpine-induced depression model, BP (100 mg/kg p.o.) showed antidepressant-like effects in one of the two antidepressant tests, but with a lower effect than amitriptyline (20 mg/kg p.o.). Conclusions: BP (100 and 200 mg/kg) showed antidepressant-like effects in acute assays and, to a lesser extent, in a reserpine-induced chronic model of depression-like behavior.},
}

@article {pmid41754025,
year = {2026},
author = {Namkung, K and Lee, K},
title = {Acceptability and Implementation Considerations for 40 Hz Auditory Stimulation Using Nature-Based Soundscapes for Cognitive Health Applications: A Qualitative Exploratory Study.},
journal = {Healthcare (Basel, Switzerland)},
volume = {14},
number = {4},
pages = {},
pmid = {41754025},
issn = {2227-9032},
support = {NRF-2025S1A5B5A16006803//the Ministry of Education of the Republic of Korea and the National Research Foundation/ ; },
abstract = {BACKGROUND/OBJECTIVES: 40 Hz sensory stimulation is being explored for cognitive health applications, but sustained use may be constrained by the listenability of simple 40 Hz auditory stimuli. We examined user-perceived acceptability and implementation considerations for 40 Hz auditory stimulation delivered by embedding a pure 40 Hz sine wave within nature-based soundscapes.

METHODS: Eleven adults aged ≥ 40 years in Seoul, Republic of Korea were assigned to waves or forest soundscapes (between-participants) and completed a within-session exposure to two conditions within the assigned set: 40 Hz-OFF (soundscape-only) and 40 Hz-ON (soundscape plus an additively layered 40 Hz sine wave). Each condition comprised seven cycles of 50 s playback and 10 s silence (~7 min) with a 10 min washout. After completing both listening blocks, participants provided brief comparative session-end ratings to aid recall and then completed a semi-structured interview focused on detectability and comparative impressions while blinded to condition identity. Following debriefing about the 40 Hz manipulation, participants completed a session-end 7-point Likert appraisal of the intended intervention stimulus (40 Hz-ON). Interview transcripts were analyzed using thematic analysis and interpreted using the Theoretical Framework of Acceptability and Proctor et al.'s implementation outcomes as sensitizing frameworks.

RESULTS: Session-end appraisals suggested that the 40 Hz-integrated soundscape (40 Hz-ON) was generally listenable, with mid-to-high comfort and immersion (medians = 5) and low unpleasantness (median = 2), while perceived artificiality spanned the full scale (range 1-7) and overall preference was moderate (median = 4). Interviews indicated that acceptability was governed by perceptual integration: natural blending supported "backgroundable" listening, whereas salient low-frequency rumble or a mechanical/artificial timbre contributed to negative reactions. Implementation-relevant themes highlighted context fit (bedtime vs. morning routines), low-friction automation (timers/scheduling), and conservative acoustic safeguards (gentle onset and default levels).

CONCLUSIONS: In a single-session evaluation among adults aged ≥ 40 years, embedding a 40 Hz sine wave within nature-based soundscapes was generally acceptable, with acceptability sensitive to perceptual integration and usage context. This qualitative study does not assess clinical or cognitive efficacy. These findings inform implementation considerations for cognitive health-oriented delivery, including space-oriented playback options, simplified automation, conservative acoustic safeguards, and coherence-supportive user guidance without overclaiming.},
}

@article {pmid41753201,
year = {2026},
author = {Hernández-Voth, A and Sayas-Catalán, J and Corral-Blanco, M and Jiménez-Gómez, M and Carvajal-Cuesta, G and Luján-Torné, M and Lalmolda-Puyol, C and Florez-Solarana, P and Villena-Garrido, V},
title = {Impact of Built-In Software Monitoring on Survival in Amyotrophic Lateral Sclerosis Patients Receiving Home Mechanical Ventilation: A Cohort Study.},
journal = {Journal of clinical medicine},
volume = {15},
number = {4},
pages = {},
pmid = {41753201},
issn = {2077-0383},
abstract = {Background/Objectives: Amyotrophic lateral sclerosis is a progressive neurodegenerative disease in which respiratory failure is the leading cause of death. Mechanical ventilation improves both survival and quality of life; however, the prognostic implications of built-in ventilator software monitoring remain insufficiently characterized. The aim of the study was to determine whether built-in ventilator software-based monitoring is associated with enhanced survival in amyotrophic lateral sclerosis subjects. Methods: Cohort study of amyotrophic lateral sclerosis subjects, stratified into two groups: those monitored through detailed built-in ventilator software and those not monitored. Clinical and ventilatory data were systematically evaluated during a 24-month follow-up. Results: Among 120 ALS subjects (57 detailed built-in ventilator software, 63 non-detailed ventilator software), median survival from diagnosis was significantly longer in the detailed built-in ventilator software group (3.42 vs. 2.12 years; p < 0.001). Survival from mechanical ventilation initiation was also significantly longer in the built-in ventilator software group (2.79 years vs. 0.78 years). Greater daily mechanical ventilation usage was associated with shorter survival (p < 0.003). Paradoxically, subjects with the lowest proportion of spontaneous inspirations exhibited superior survival outcomes (p = 0.04). Neither persistent leaks nor asynchronies were independently predictive of survival. Conclusions: BVS-monitoring was associated with improved survival in amyotrophic lateral sclerosis subjects receiving home mechanical ventilation. Its integration into clinical practice may enable timely, data-driven ventilatory adjustments, ultimately contributing to more individualized and optimized patient management.},
}

@article {pmid41752118,
year = {2026},
author = {Kurdi, MA and Alotaibi, H and Alkhuraymi, AT and Aldahery, LN and Alhawaj, AF and Aldali, HJ},
title = {Amyotrophic Lateral Sclerosis (ALS) Genetics and Microbiota: A Comprehensive Review.},
journal = {International journal of molecular sciences},
volume = {27},
number = {4},
pages = {},
pmid = {41752118},
issn = {1422-0067},
mesh = {*Amyotrophic Lateral Sclerosis/genetics/microbiology/therapy ; Humans ; Genetic Therapy ; *Gastrointestinal Microbiome ; C9orf72 Protein/genetics ; Animals ; Superoxide Dismutase-1/genetics ; Mutation ; RNA-Binding Protein FUS/genetics ; DNA-Binding Proteins/genetics ; },
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a severe, progressive neurodegenerative disorder characterized by the loss of upper and lower motor neurons, affecting 0.5 to 2.6 per 100,000 people, with a median survival of 2 to 5 years. It is increasingly seen as a multisystem disorder, sharing essential clinicopathological features with Frontotemporal Dementia (FTD). This convergence arises from overlapping molecular processes, including severe oxidative stress, glutamate-mediated excitotoxicity, mitochondrial dysfunction, and widespread aggregated TDP-43 proteinopathy in both sporadic and familial cases. Several key genetic factors have been identified, particularly mutations in C9orf72, SOD1, TARDBP, and FUS, which serve as important targets for novel treatments, such as Tofersen, a recently approved SOD1-specific antisense oligonucleotide (ASO) gene therapy. Additionally, there is increasing evidence of the gut-brain connection. Dysbiosis, involving species such as Akkermansia muciniphila, and lower levels of neuroprotective metabolites, such as nicotinamide, may affect the course of the disease. As a result, treatment strategies are shifting toward a personalized approach. This includes using gene therapy, ranging from ASOs and RNA interference (RNAi) to new CRISPR-based genome editing. It also involves exploring microbiome-modulating treatments, such as specific probiotics and Fecal Microbiota Transplantation (FMT). While microbiome and gene therapies remain largely experimental, their potential is promising, as highlighted by the recent approval of Tofersen. These novel approaches could be further enhanced and guided by more robust diagnostic criteria and by investigating early multimodal treatment strategies to slow the progression of this complex disease.},
}

*Amyotrophic Lateral Sclerosis/genetics/microbiology/therapy
Humans
Genetic Therapy
*Gastrointestinal Microbiome
C9orf72 Protein/genetics
Animals
Superoxide Dismutase-1/genetics
Mutation
RNA-Binding Protein FUS/genetics
DNA-Binding Proteins/genetics

@article {pmid41752089,
year = {2026},
author = {Hall, B and Castelli, L and Higginbottom, A and He, J and Zou, LN and Walker, H and Yagüe-Capilla, M and Wong, KE and Burrows, DJ and George, J and Hamer, K and Tanner, JM and Kyrgiou-Balli, E and Ross, R and Garland, H and Tonkiss, E and George, R and Webster, CP and Smith, EF and Timmons, HO and Allsop, J and Stefanidis, N and Ward, BD and Lin, YH and Highley, JR and Azzouz, M and West, RJH and Rudd, SG and Vos, KJ and Shaw, PJ and Hautbergue, GM and Allen, SP},
title = {Antisense Dipeptide Repeat Proteins Drive Widescale Purine Metabolism Aberration in C9orf72 Amyotrophic Lateral Sclerosis via ADA.},
journal = {International journal of molecular sciences},
volume = {27},
number = {4},
pages = {},
pmid = {41752089},
issn = {1422-0067},
support = {SBF005\1064/AMS_/Academy of Medical Sciences/United Kingdom ; Allen 887-791//MND Association/ ; Allen/Jun23/964-793//MND Association/ ; West/Oct22/909-792//MND Association/ ; BRC-203321//NIHR/ ; NF-SI-0617-10077//NIHR/ ; AMBRoSIA PJS 972-797//MND Association/ ; TJ2022-0063//Swedish Childhood Cancer Fund/ ; 19-0056-JIA//Swedish Cancer Society/ ; 23-2782-Pj//Swedish Cancer Society/ ; 260 (AS-PG-15-023)/ALZS_/Alzheimer's Society/United Kingdom ; MR/S025979/1/MRC_/Medical Research Council/United Kingdom ; MR/M013251/1/MRC_/Medical Research Council/United Kingdom ; MR/Z504701/1/MRC_/Medical Research Council/United Kingdom ; DEVOS/APR18/862-79//MND Association/ ; ARUK-PG2018B-005//Alzheimer's Research UK/ ; MR/W00416X/1/MRC_/Medical Research Council/United Kingdom ; },
mesh = {*Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology ; *C9orf72 Protein/genetics/metabolism ; Humans ; *Adenosine Deaminase/metabolism/genetics ; *Purines/metabolism ; Animals ; Mice ; *Dipeptides/genetics/metabolism ; Astrocytes/metabolism ; DNA Repeat Expansion ; Male ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterised by the death of motor neurons leading to paralysis and death, generally 3-5 years post-symptom onset. The most frequent genetic cause of ALS is a hexanucleotide repeat expansion (HRE) in the chromosome 9 open reading frame 72 (C9orf72) gene, that has three major hypothesised pathological mechanisms including the production of dipeptide repeat proteins (DPRs). Our laboratory has previously identified purine metabolism dysfunction in induced neural progenitor cell-derived astrocytes (iAstrocytes) from C9orf72 ALS (C9-ALS) cases (C9-iAstrocytes), driven by loss of the enzyme adenosine deaminase (ADA). Here, we have demonstrated that loss of ADA along with changes to ecto-5'-nucleotidase and hypoxanthine-guanine phosphoribosyl transferase led to disruption in purine metabolite levels including purine dNTP output. These changes were recapitulated in patient CSF, whilst loss of ADA was recapitulated in patient white matter. Immunofluorescence also demonstrated purinosome formation dysfunction in C9-iAstrocytes. These changes are likely driven by DPRs as ADA loss was recapitulated in in vitro and in vivo DPR models. Finally, ADA levels could be recovered by reducing DPR levels either by inhibiting serine/arginine-rich splicing factor 1 or overexpressing RuvB-like 2. Our data demonstrate that DPR production negatively affects purine function in C9-ALS suggesting a potentially pivotal role for purine metabolism dysfunction in C9-ALS pathology.},
}

*Amyotrophic Lateral Sclerosis/metabolism/genetics/pathology
*C9orf72 Protein/genetics/metabolism
Humans
*Adenosine Deaminase/metabolism/genetics
*Purines/metabolism
Animals
Mice
*Dipeptides/genetics/metabolism
Astrocytes/metabolism
DNA Repeat Expansion
Male

@article {pmid41751955,
year = {2026},
author = {Luong, DT and Niu, C and Kim, E and Tanji, N and Duong, I and Galero, B and Zhang, YJ and Bennett, CL and La Spada, AR},
title = {PPAR-Delta Agonist Therapies Did Not Rescue Hallmark Disease Phenotypes in Two Sets of Preclinical Trials in ALS TDP-43 and C9orf72 Model Mice.},
journal = {International journal of molecular sciences},
volume = {27},
number = {4},
pages = {},
pmid = {41751955},
issn = {1422-0067},
support = {W81XWH-20-1-0154//United States Department of Defense/ ; },
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/drug therapy/genetics/metabolism/pathology ; Mice ; *PPAR delta/agonists/metabolism ; Disease Models, Animal ; Mice, Transgenic ; *C9orf72 Protein/genetics/metabolism ; Phenotype ; *DNA-Binding Proteins/genetics/metabolism ; Male ; Neurofilament Proteins/blood ; Humans ; },
abstract = {Peroxisome-proliferator-activated receptor delta (PPARδ) regulates metabolic, mitochondrial, and inflammatory pathways implicated in neurodegeneration, making it an attractive therapeutic target for amyotrophic lateral sclerosis (ALS). In this study, we evaluated two PPARδ agonists, KD3010 and T3D-959, in two established ALS/FTD mouse models: an AAV-mediated C9orf72 G4C2-repeat expansion model (C9-149R) and the TDP-43[Q331K] transgenic model. Drug treatment was initiated prior to the emergence of key disease features and continued for 9-10 months. Comprehensive behavioral, neuropathological, and biomarker analyses revealed marked differences between the two models. C9-149R mice exhibited reduced body weight and subtle behavioral alterations without robust motor deficits, whereas TDP-43[Q331K] mice developed pronounced, progressive motor and cognitive impairments accompanied by a ~7-fold elevation in plasma neurofilament light chain (NfL). Despite effective target engagement-particularly for T3D-959-neither PPARδ agonist improved motor performance, cognitive behavior, neuroanatomical measures, plasma NfL levels, or disease-associated molecular phenotypes in either model. Prolonged KD3010 treatment resulted in loss of target engagement, consistent with drug tolerance, while T3D-959 sustained PPARδ activation without therapeutic benefit. Together, these findings demonstrate that PPARδ agonism is insufficient to modify disease progression in these ALS/FTD mouse models and underscore the importance of publishing well-powered negative preclinical studies to refine therapeutic strategies for ALS.},
}

Animals
*Amyotrophic Lateral Sclerosis/drug therapy/genetics/metabolism/pathology
Mice
*PPAR delta/agonists/metabolism
Disease Models, Animal
Mice, Transgenic
*C9orf72 Protein/genetics/metabolism
Phenotype
*DNA-Binding Proteins/genetics/metabolism
Male
Neurofilament Proteins/blood
Humans

@article {pmid41751793,
year = {2026},
author = {Ptáček, O and Musil, Z and Guarnieri, G and Vrbacká, A and Moudrá, P and Zlámalová, A and Röszlerová, P and Tonhajzer, M and Musil, V and Morelli, A and Zach, P},
title = {Amyotrophic Lateral Sclerosis: The State of the Art on Treatments and the Therapeutic Role of the Intestinal Microbiome in Human Studies.},
journal = {International journal of molecular sciences},
volume = {27},
number = {4},
pages = {},
pmid = {41751793},
issn = {1422-0067},
support = {Cooperatio 39 - Oncology and Haematology//Charles University/ ; Cooperatio 33-Intensive Care Medicine//Charles University/ ; Cooperatio 36-Medical Diagnostics and Basic Medical Sciences//Charles University/ ; #NEXTGENERATIONEU//European Commission/ ; MNESYS (PE0000006) - A Multiscale integrated approach to the study of the nervous system in health and disease (DR. 1553 11.10.2022)//Ministry of University and Research (MUR), National Recovery and Resilience Plan (NRRP)/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy/microbiology ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation/methods ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a common neurodegenerative disorder; to date, there is no long-term effective treatment. Recently, a relationship has been discovered between the human intestinal microbiome and the pathogenesis of ALS, on which basis faecal microbiota transplantation (FMT) has been proposed as a potential treatment for ALS. In this review, we compare three existing case studies examining the effect of FMT on the course of ALS, highlighting differences in methodology and results. In two of the studies, a halt in the progression of ALS symptoms was observed following FMT, accompanied by improvement in patient health. However, in the third and largest study, no significant effect of FMT was observed. The possible explanation for this discrepancy may be the intentional depletion of intestinal microorganisms using antibiotics prior to FMT in the third study. Future studies and/or completion of the ongoing clinical studies will help clarify the therapeutic effectiveness of FMT in ALS patients.},
}

Humans
*Amyotrophic Lateral Sclerosis/therapy/microbiology
*Gastrointestinal Microbiome
*Fecal Microbiota Transplantation/methods

@article {pmid41751374,
year = {2026},
author = {Trabulo, A and Sousa, P and Alvites, R and Maurício, AC},
title = {Mesenchymal Stem Cell-Based Therapies Applied in Neurological Diseases: A Systematic Review.},
journal = {Biomedicines},
volume = {14},
number = {2},
pages = {},
pmid = {41751374},
issn = {2227-9059},
abstract = {Background/Objectives: Neurodegenerative diseases (NDs) have a severe impact on patients' quality of life, and effective treatments remain limited. As the focus is on treating the symptoms, the root cause of the problem is commonly not addressed. Mesenchymal stem cells show an emerging potential due to the ability for self-renewal combined with their capability for differentiation into various cell lines, which makes them a strong candidate for regenerative therapies in general, and for application in neurological issues in particular. This article provides an overview of the safety, efficacy, and challenges associated with the use of mesenchymal stem cells (MSCs) and their derived secretome in clinical and preclinical models of Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS). Methods: A systematic search was conducted on PubMed to identify published studies providing clinical and preclinical evidence on the use of MSCs in neurodegenerative disorders. Results: Overall, the literature consistently indicates that MSCs and their derivatives exert disease-modifying effects across multiple NDs. Across AD, PD, HD and ALS, preclinical studies uniformly report improvements in behavioural outcomes, attenuation of neuroinflammation, and neuroprotective effects, largely mediated by MSCs' paracrine signalling rather than direct cell replacement. Clinical studies to date consistently support the safety and feasibility of MSC-based therapies, while efficacy signals remain modest, heterogeneous and predominantly short-term, highlighting the need for larger, well-controlled trials. Conclusions: Integration of genetic engineering, preconditioning, and EV technology may represent an emerging therapeutic approach that may complement existing neuroregeneration treatments, offering a scalable and minimally invasive frontier to improve long-term clinical outcomes in patients with AD, PD, HD, and ALS.},
}

@article {pmid41751343,
year = {2026},
author = {Iyer, MR and Zhao, B and He, X and Camacho, D and Wei, Z and Deng, J and Mitchell, CS},
title = {An Artificial Intelligence-Driven Multimorbidity Framework Reveals a Shared Metabolic and Immune Core Across Alzheimer's Disease, Amyotrophic Lateral Sclerosis, and Frontotemporal Dementia.},
journal = {Biomedicines},
volume = {14},
number = {2},
pages = {},
pmid = {41751343},
issn = {2227-9059},
support = {1944247//National Science Foundation/ ; R35GM152245/NH/NIH HHS/United States ; U19AG056169/NH/NIH HHS/United States ; 253558//Chan Zuckerberg Initiative/ ; },
abstract = {Background/Objectives: Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD) share molecular features yet differ clinically, suggesting underlying systems-level commonalities. We aimed to characterize shared and disease-specific multimorbidity architectures across AD, ALS, and FTD using an artificial intelligence-driven literature-based semantic network. Methods: We applied SemNet 2.0, constructed from over 35 million PubMed abstracts, to analyze disease and syndrome (DSYN) and pharmacological substance (PHSU) nodes. Nodes were ranked using HeteSim and mapped to a harmonized 13-category mechanistic ontology. We quantified pairwise disease intersections, ontology-level enrichment, rank similarity, and intersection-disease alignment, and constructed an integrated multimorbidity priority landscape integrating disease-specific and intersection-level hierarchies. Results: Across AD, ALS, and FTD, a convergent multimorbidity architecture centered on a shared metabolic and immune core was identified, accompanied by prominent neurobehavioral processes and intermediate systems including gastrointestinal, endocrine, hematological, hepatic, and sensory pathways. Disease-specific signatures shaped distinct vulnerability profiles within this shared structure, including cardiovascular enrichment in AD, neuromuscular and toxin-related pathways in ALS, and coupled neurobehavioral-metabolic features in FTD. PHSU patterns reinforced these findings, with centrally positioned compounds predominantly targeting inflammatory, metabolic, or neuromodulatory processes. Conclusions: These findings position AD, ALS, and FTD within a unified, AI-derived multimorbidity framework. This ontology-guided approach provides a computational, hypothesis-generating foundation for multimorbidity-aware biomarker discovery, risk stratification, and cross-disease therapeutic exploration in neurodegenerative disease.},
}

@article {pmid41750455,
year = {2026},
author = {Bustos, C and Yuste, JR and Aguinaga, A and Parra, A and Carmona-Torre, F and Azanza, JR and Lacasa, C and Del Pozo, JL},
title = {Timing of Antimicrobial Lock Replacement for Gram-Positive Port Infections: Results of a Randomized Trial.},
journal = {Antibiotics (Basel, Switzerland)},
volume = {15},
number = {2},
pages = {},
pmid = {41750455},
issn = {2079-6382},
support = {EC10-329//Instituto de Salud Carlos III/ ; },
abstract = {Background: Conservative management of port-related bacteremia often includes locally administered antimicrobials, known as antimicrobial lock therapy (ALT). Current guidelines recommend daily replacement of antimicrobial lock solutions (ALSs). We aimed to evaluate whether ALSs could remain effective with extended dwell times of up to 10 days. Methods: In this randomized clinical trial, patients with noninfected, recently implanted ports were assigned to one of five ALS dwell-time groups, ranging from 1 to 10 days. Each ALS contained heparin plus an antimicrobial at standard intraluminal concentrations: vancomycin 2 mg/mL, teicoplanin 10 mg/mL, linezolid 1.8 mg/mL, daptomycin 5 mg/mL, or tigecycline 4.5 mg/mL. The primary endpoint was the time at which intraluminal drug concentrations decreased below 1 mg/mL (ClinicalTrials.gov NCT01592032). Results: Vancomycin and linezolid concentrations fell significantly below 1 mg/mL after 3 days of dwell time. Daptomycin and tigecycline concentrations decreased significantly after 7 days but remained above 1 mg/mL. Teicoplanin concentrations did not decline significantly after 7 days. Conclusions: Optimal ALS dwell time depends on the antimicrobial agent. Vancomycin and linezolid locks require daily replacement, whereas daptomycin, tigecycline, and teicoplanin locks maintain therapeutic concentrations for up to 7 days. These findings support individualized ALS replacement strategies, potentially reducing the need for daily interventions.},
}

@article {pmid41750323,
year = {2026},
author = {Dong, L and Li, X and Li, A and Yi, J and Vockery, Y and Chang, Y and Pan, Z and Brotto, M and Zhou, J},
title = {Absence of Neuromuscular Dysfunction in Mice with Gut Epithelium-Restricted Expression of ALS Mutation hSOD1[G93A].},
journal = {Biomolecules},
volume = {16},
number = {2},
pages = {},
pmid = {41750323},
issn = {2218-273X},
support = {R01NS105621//National Institute of Health/ ; R01HL138570//National Institute of Health/ ; AL170061(W81XWH1810684)//United States Department of Defense/ ; 16-IIP-288//Bank of America/ ; },
mesh = {Animals ; *Amyotrophic Lateral Sclerosis/genetics/pathology/physiopathology/metabolism ; Mice ; Mice, Transgenic ; Humans ; *Superoxide Dismutase-1/genetics/metabolism ; Mutation ; Disease Models, Animal ; *Intestinal Mucosa/metabolism/pathology ; Muscle, Skeletal/metabolism ; Motor Neurons/metabolism/pathology ; Neuromuscular Junction ; },
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a devastating neuromuscular disorder characterized by the progressive loss of motor neurons and skeletal muscle, ultimately leading to respiratory failure and death, typically within 3-5 years following diagnosis. While the death of motor neurons is the pathological hallmark, ALS is increasingly recognized as a systemic disorder involving non-motor systems. Gastrointestinal dysfunction has been widely observed in both ALS patients and animal models. However, because gut abnormalities and neuromuscular degeneration are intertwined during ALS disease progression, it remains unclear whether these gut abnormalities are merely a consequence of neuromuscular degeneration or whether they play a crucial role in initiating it. In this study, we investigated whether an ALS-associated mutation expressed exclusively in the gut can directly affect neuromuscular function. We generated a novel transgenic mouse model, Gut-hG93A, which overexpresses the human ALS mutation hSOD1[G93A] specifically in the epithelial cells of the intestine at a level comparable to the endogenous mouse SOD1. We found that the specific overexpression of hSOD1[G93A] in gut epithelial cells did not cause abnormalities in the structure of the tight junctions or in gut permeability. Furthermore, there were no significant differences between Gut-hG93A and control mice regarding lifespan, body weight, or neuromuscular activities, including grip strength, daily travel distance and in vivo muscle contractility. These findings suggest that the ALS-associated hSOD1[G93A] mutation, when expressed solely in the gut epithelium, is not sufficient to initiate neuromuscular degeneration of systemic ALS-like pathology.},
}

Animals
*Amyotrophic Lateral Sclerosis/genetics/pathology/physiopathology/metabolism
Mice
Mice, Transgenic
Humans
*Superoxide Dismutase-1/genetics/metabolism
Mutation
Disease Models, Animal
*Intestinal Mucosa/metabolism/pathology
Muscle, Skeletal/metabolism
Motor Neurons/metabolism/pathology
Neuromuscular Junction

@article {pmid41750236,
year = {2026},
author = {Eisen, A},
title = {Exploring the ALS Multistep Model.},
journal = {Brain sciences},
volume = {16},
number = {2},
pages = {},
pmid = {41750236},
issn = {2076-3425},
abstract = {ALS is a multistep disease, in which (epi)genetic, environmental, and age-related processes, including senescence, converge over decades to reduce resilience resulting in self-sustaining symptomatic disease. The multistep model visualizes five to six impactful events in sporadic ALS, but fewer in those carrying high-penetrance mutations, such as SOD1, FUS, or C9orf72 expansions. The timing, duration, and cumulative effects of specific steps are presumed to have individual variability but, the steps themselves are inferred since they have not been observed and remain agnostic as to biological identity. Nevertheless, the model gives an opportunity to integrate genetics, aging, environmental exposures, and systems-level vulnerability into a single framework. Acting as step modifiers, environmental exposures including trauma lower the threshold for step acquisition, accelerate the accumulation of steps, influence the anatomical site of disease onset, and unmask preclinical disease. Because ALS emerges from the gradual collapse of multiple layers of biological robustness, tackling a single pathway will be insufficient and the multistep model forces a reconsideration of therapeutic timing and strategies. Protection against early-life insults, anti-aging, and anti-senescent therapies may curtail step accumulation preventing ALS from exceeding threshold and disease manifestation.},
}

@article {pmid41750189,
year = {2026},
author = {Ray, SK},
title = {'Molecular and Cellular Neuroscience': Impacts of Eight Highly Cited Articles Published in This Section of Brain Sciences in 2024.},
journal = {Brain sciences},
volume = {16},
number = {2},
pages = {},
pmid = {41750189},
issn = {2076-3425},
abstract = {This year, the selection criteria for highly cited articles in the 'Molecular and Cellular Neuroscience' section of Brain Sciences were focused on publications that achieved a citation count of 10 or more during 2024. Applying this metric, the Editorial Office, in collaboration with myself as Associate Editor of the 'Molecular and Cellular Neuroscience' section of the journal, identified eight articles that not only exemplified the mission of this section but also made significant scientific contributions by advancing our current understanding of the molecular and cellular mechanisms underlying major and rare neurological disorders. These articles encompass miscellaneous topics, including Alzheimer's disease (AD), chronic alcoholism, glioblastoma multiforme (GBM), amyotrophic lateral sclerosis (ALS), cognitive impairment, cerebrovascular disease, and Rett syndrome (RTT). Importantly, several contributions highlight experimental therapeutic strategies aimed at mitigating pathogenic mechanisms, offering promising avenues for translational research and future clinical applications.},
}

@article {pmid41750144,
year = {2026},
author = {Huang, X and Xia, K and Ye, S and Yang, Q and Fan, D},
title = {Enlarged Perivascular Spaces (EPVS) and the Risk of Amyotrophic Lateral Sclerosis (ALS): Evidence for Overlapping Genetic Signals in White Matter Without Causal Links.},
journal = {Brain sciences},
volume = {16},
number = {2},
pages = {},
pmid = {41750144},
issn = {2076-3425},
support = {81873784, 82071426, 82401670//National Natural Science Foundation of China/ ; BYSYDL2019002//Clinical Cohort Construction Program of Peking University Third Hospital/ ; there is no number of this funding.//the special fund of the National Clinical Key Specialty Construction Program, P. R.China(2024)/ ; },
abstract = {Background/Objectives: Emerging evidence suggests that enlarged perivascular spaces (EPVS), which play a significant role in brain fluid exchange and waste removal, may be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). In this study, we aimed to explore the shared genetic link and causal effect between EPVS and ALS. Methods: This study used publicly available summary data from the largest and most recent genome-wide association studies (GWAS) on EPVS (n = 40,095) and ALS (n = 138,086) in European populations. EPVS were assessed in the hippocampus (EPVS-HIP), basal ganglia (EPVS-BG), and white matter (EPVS-WM). We used linkage disequilibrium score regression (LDSC) to investigate the genetic correlation. Multi-trait analysis of GWAS (MTAG), Cross-Phenotype Association (CPASSOC) analysis, and genetic colocalization analysis were performed to identify shared risk loci. Bidirectional Mendelian randomization analysis was used to investigate the causal relationship. Results: A negative genetic correlation was observed between EPVS-WM and ALS after Bonferroni correction (rg = -0.24, p < 0.01). No significant correlations were observed between ALS and EPVS-HIP (rg = -0.03, p = 0.79) or EPVS-BG (rg = 0.01, p = 0.91). Four significant loci including rs113247976 in KIF5A and rs118082508 in SDR9C7 were identified as potential pleiotropic loci of the relationship. None of these loci demonstrated evidence of genetic colocalization. Furthermore, Mendelian randomization analysis revealed no causative effect in either direction. Conclusions: EPVS-WM and ALS may share part of their genetic architecture, but no evidence for a causal relationship was observed. Future research is needed to further refine these relationships.},
}

@article {pmid41749825,
year = {2026},
author = {De Simoni, O and Scarpa, M and Cavallin, F and Kotsafti, A and Marchegiani, F and Stepanyan, A and Tussardi, G and Rosato, A and Spolverato, G and Angriman, I and Urso, EDL and Ruffolo, C and Saadeh, LM and Maretto, I and Bao, QR and Negro, S and Vignotto, C and Facci, L and Rivella, G and D'Angelo, A and Matteazzi, A and Galuppini, F and Guzzardo, V and Salmaso, R and Pellegrini, V and Brignola, S and Ceccon, C and Stecca, T and Pozza, A and Massani, M and Pilati, P and Gruppo, M and Franzato, B and Cataldo, I and Portale, G and Cipollari, C and Zuin, M and Laurino, L and Dal Santo, L and Pirozzolo, G and Recordare, A and Ceccarini, L and Antoniutti, M and Marinelli, L and Brolese, A and Barbareschi, M and Bertalot, G and Ortenzi, M and Guerrieri, M and Zizzo, M and Dell'Atti, L and Guerriero, S and Piccioli, A and Pozza, G and Godina, M and Mondi, I and Verdi, D and Da Lio, C and Noaro, G and Cola, R and Bordignon, G and Merenda, R and Becherucci, G and Gavagna, L and Candioli, S and Tagliente, G and Tedeschi, U and Parini, D and Salmaso, B and Businello, G and Di Cristoforo, L and Bergamo, F and Porzionato, A and Scognamiglio, F and Bardini, R and Pucciarelli, S and Agostini, M and Chiminazzo, V and Gregori, D and Di Camillo, B and Castagliuolo, I and Dei Tos, AP and Fassan, M and Scarpa, M},
title = {IMMUNOREACT 4: Peritumoral Microenvironment Associated with Anastomotic Leaks After Surgery for Rectal Cancer.},
journal = {Cancers},
volume = {18},
number = {4},
pages = {},
pmid = {41749825},
issn = {2072-6694},
support = {23381//AIRC IG 2019/ ; },
abstract = {Background: Anastomotic leaks (ALs) remain a critical complication after rectal cancer surgery. Emerging evidence suggests that local immune dysregulation may play a key role in anastomotic healing. We investigated the immune microenvironment of histologically normal, tumor-adjacent rectal mucosa-a tumor-conditioned field-as a potential substrate for AL predisposition. Methods: IMMUNOREACT 4 is a sub-analysis of the IMMUNOREACT project (clinicaltrials.gov NCT04915326 and NCT04915326), a multicenter translational study evaluating immune features of histologically normal, tumor-adjacent rectal mucosa of patients undergoing colorectal anastomosis. A prospective cohort (n = 121) was analyzed using flow cytometry, in addition to a retrospective cohort (n = 262) using immunohistochemistry. Immune markers of epithelial activation and lymphocyte subsets were compared between patients with and without postoperative ALs. Exploratory predictive models combining immune and clinical variables were developed and evaluated using discrimination, calibration and decision curve analyses. Results: At flow cytometry, the CK[+]HLAabc[+] MFI (AUC 0.66, 95% CI 0.52-0.80), CD8[+]CD38[+] cell rate (AUC 0.65, 95% CI 0.52-0.78) and CD3[+]CTLA4[+] cell rate (AUC 0.65, 95% CI 0.51-0.80) showed moderate predictive potential for ALs. In immunohistochemistry, CD3[+] (AUC 0.57, 95% CI 0.54-0.60), CD8[+] (AUC 0.57, 95% CI 0.52-0.62), CD8β[+] (AUC 0.59, 95% CI 0.53-0.65) and Tbet[+] (AUC 0.60, 95% CI 0.56-0.64) showed some predictive ability for ALs. The model including CD8β[+], the BMI, neutrophile/lymphocyte ratio and tumor location had an AUC of 0.67 (95% CI 0.62-0.72). Conclusions: Immune activation within histologically normal, tumor-adjacent rectal mucosa-characterized by epithelial HLA upregulation and cytotoxic or Th1 T cell infiltration-is associated with postoperative ALs. Although predictive accuracy is limited, these findings support the concept that a tumor-conditioned immune microenvironment may predispose patients to impaired anastomotic healing. Integration of mucosal immune profiling with clinical variables represents a promising exploratory approach that warrants further prospective validation.},
}

@article {pmid41749139,
year = {2026},
author = {Sun, Q and Wang, H and Deng, G and Du, Y and Ma, T and Ding, J and Xia, Z and Jiang, Y and Huang, Y and Huang, X},
title = {Nomogram prediction model for prognosis of patients with amyotrophic lateral sclerosis.},
journal = {BMC neurology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12883-026-04741-8},
pmid = {41749139},
issn = {1471-2377},
support = {320.6750.18456//Wu Jieping Medical Foundation/ ; 320.6750.18456//Wu Jieping Medical Foundation/ ; 320.6750.18456//Wu Jieping Medical Foundation/ ; 320.6750.18456//Wu Jieping Medical Foundation/ ; 320.6750.18456//Wu Jieping Medical Foundation/ ; 320.6750.18456//Wu Jieping Medical Foundation/ ; 320.6750.18456//Wu Jieping Medical Foundation/ ; 320.6750.18456//Wu Jieping Medical Foundation/ ; },
}

@article {pmid41748409,
year = {2026},
author = {Anzilotti, S and Valente, V and Brancaccio, P and Franco, C and Casamassa, A and Lombardi, G and Palazzi, A and Conte, A and Paladino, S and Canzoniero, LMT and Annunziato, L and Pierantoni, GM and Pignataro, G},
title = {Corrigendum to "Chronic exposure to l-BMAA cyanotoxin induces cytoplasmic TDP-43 accumulation and glial activation, reproducing an amyotrophic lateral sclerosis-like phenotype in mice" [Biomed. Pharmacother. 167 (2023) 115503].},
journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie},
volume = {196},
number = {},
pages = {119161},
doi = {10.1016/j.biopha.2026.119161},
pmid = {41748409},
issn = {1950-6007},
}

@article {pmid41747658,
year = {2026},
author = {Fernandes, GL and Orssatto, LBR and Pinto, MD and Henkin, JS and Shandiz, E and McCombe, PA and Henderson, RD and Trajano, GS},
title = {Maximal motor unit firing rates decline with amyotrophic lateral sclerosis progression.},
journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology},
volume = {185},
number = {},
pages = {2111697},
doi = {10.1016/j.clinph.2026.2111697},
pmid = {41747658},
issn = {1872-8952},
abstract = {OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is characterised by progressive degeneration of upper and lower motor neurons and their motor units (MUs). MU loss is compensated by collateral sprouting and reinnervation of muscle fibres. There is limited information about the properties of these surviving MUs as these processes take place. High-density surface electromyography (HD-sEMG) decomposition enables non-invasive analysis of individual MU firing behaviour during maximal voluntary contractions and assess their changes with ALS progression.

METHODS: Thirty-nine individuals with ALS (24 men; mean age 63 ± 16 years) completed up to five visits (interval 20.0 ± 7.9 weeks). Tibialis anterior HD-sEMG recordings during maximal contractions were decomposed into individual MU spike trains, from which maximal firing rates were quantified. Muscle strength was assessed with the Medical Research Council (MRC) scale, and global function with the revised ALS Functional Rating Scale (ALSFRS-R).

RESULTS: Maximal MU firing rates declined significantly over time [-0.32 Hz/month, (95% CI -0.44; -0.19)], regardless of MRC scores. Across participants, maximal firing rates decreased by 2.38 Hz (1.78; 2.98) for each 1-point reduction in MRC and by 0.54 Hz for each ALSFRS-R point (-0.83; -0.26).

CONCLUSION: These findings demonstrate that maximal MU firing rates decline as ALS progresses, suggesting that the surviving motor unit undergo progressive pathophysiological changes as motor neurons degenerate. HD-sEMG MU firing-rates analysis appeared more sensitive than MRC in detecting early deterioration in muscle decline.

SIGNIFICANCE: Maximal firing rates analysis has the potential to serve as a quantitative clinical biomarker of neuromotor system degeneration, complementing global functional scales in clinical monitoring.},
}

@article {pmid41747520,
year = {2026},
author = {Ammari, F and Le Penglau, R and Bouhier, M and Neff, D},
title = {Characterization of long-term atmospheric corrosion of iron in indoor and outdoor conditions using Raman spectroscopy coupled to multivariate curve resolution-alternating least squares.},
journal = {Talanta},
volume = {305},
number = {},
pages = {129569},
doi = {10.1016/j.talanta.2026.129569},
pmid = {41747520},
issn = {1873-3573},
abstract = {This study presents a characterization of long-term atmospheric corrosion layers formed on historical iron samples from two cathedrals exposed to distinct environments: outdoor-exposed low-alloy steel clamps from Metz Cathedral and indoor-exposed iron reinforcements from Amiens Cathedral, both aged over 500 years. To address the complexity and heterogeneity of the corrosion products, Raman micro-spectroscopy was combined with multivariate curve resolution-alternating least squares (MCR-ALS) to extract pure spectral components and their spatial distribution, and estimate their relative contributions within the corrosion matrix. For the Amiens sample, MCR-ALS was first initialized using laboratory-acquired reference spectra of pure phases. The same dataset was then reprocessed using component spectra extracted from non-negative matrix factorization (NMF) as a blind initialization. The comparison of the results demonstrated that reliable and chemically consistent results can be obtained even without experimentally measured reference spectra, offering a robust solution for the analysis of complex mixtures. To further validate this approach in a more complex system, the Metz sample was analyzed using a fully blind NMF-based initialization, confirming the method's robustness across varying environmental contexts and over extended timescales. Finally, the identified corrosion phases and their spatial distributions were compared with previous studies, revealing strong agreement and thereby reinforcing the reliability of the approach.},
}

@article {pmid41747474,
year = {2026},
author = {Kaji, R and Ishida, T and Izumi, Y},
title = {Response to letter to the editor "Comment on: Clinical safety of ultra-high-dose methylcobalamin in patients with amyotrophic lateral sclerosis: Open-label extension of a phase 2/3 randomized controlled study".},
journal = {Journal of the neurological sciences},
volume = {483},
number = {},
pages = {125792},
doi = {10.1016/j.jns.2026.125792},
pmid = {41747474},
issn = {1878-5883},
}

@article {pmid41746412,
year = {2026},
author = {Tarazona-Santabalbina, FJ and Belenguer-Varea, A and Borrás-Blasco, J and García-Tercero, E and Martin, ML and Prior, NP and Mariscal, G and Valcuende-Rosique, A},
title = {Safety profile of tofersen in amyotrophic lateral sclerosis: a systematic review and meta-analysis.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {3},
pages = {},
pmid = {41746412},
issn = {1590-3478},
}

@article {pmid41745965,
year = {2026},
author = {Haroun, M and Tratrat, C and Mathew, RT and Munir, M and Sattar, MN and Shawky, M and Kochkar, H and Aldakhilallah, ON and Ghafoor, A and Turk, KGB and Geronikaki, A and Ghazzawy, HS},
title = {Avian Candidiasis: A Comprehensive Review of Pathogenesis, Diagnosis, and Control.},
journal = {Veterinary sciences},
volume = {13},
number = {2},
pages = {},
pmid = {41745965},
issn = {2306-7381},
support = {Grant number: KFU260519//Deanship of Scientific Research, Vice Presidency for Graduate Studies and Scientific Research, King Faisal University, Saudi Arabia/ ; },
abstract = {This review is a comprehensive investigation of avian candidiasis, mainly caused by Candida albicans, although the prevalence of non-albicans Candida species has increased in domestic and wild birds. Avian candidiasis causes significant economic losses in poultry production through increased mortality, cost of treatments, and reduced growth rates, particularly in young birds and intensive farming operations. The pathogenesis section provides a description of the molecular virulence factors such as adhesin-mediated attachment (ALS, Agglutinin-Like Sequence family; HWP1, Hyphal Wall Protein 1), yeast-to-hypha morphogenesis, tissue damage by Candidalysin, biofilm formation on mucosal and abiotic surfaces, and secreted hydrolytic enzymes including secreted aspartyl proteinases (SAPs) and phospholipases. The identified predisposing factors include immunosuppression, malnutrition, abuse of antibiotics, bad husbandry, and crop stasis. The diagnostic methods discussed encompass cytological analysis and fungal culture on selective media to more sophisticated methods of molecular analysis (PCR, MALDI-TOF MS, and NGS). Antifungal susceptibility investigations indicate that nystatin and amphotericin B are still very effective against most avian isolates and that resistance to the azoles is on the rise, especially with respect to the non-albicans Candida species. Nystatin is still the first-line treatment of localized infections; azoles are still used for resistant or systemic infections despite their hepatotoxicity. Sanitation, proper nutrition, and proper use of antimicrobials are essential to prevent diseases. The knowledge gaps comprise the absence of avian-specific pharmacokinetic information, poor knowledge of species-species virulence phenotypes, and the lack of point-of-care diagnostics. The need to have integrated One Health surveillance systems is emphasized by the zoonotic potential of the avian Candida reservoirs.},
}