@article {pmid42135015,
year = {2026},
author = {Bate, J and Fealey, J and Young, C and McArdle, A and Staunton, CA and Close, GL},
title = {Sport-related trauma and motor neurone disease: a scoping review of epidemiology, mechanisms and future directions.},
journal = {British journal of sports medicine},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjsports-2025-111410},
pmid = {42135015},
issn = {1473-0480},
abstract = {OBJECTIVE: To map existing epidemiological evidence assessing the relationship of sport-related trauma and Motor Neurone Disease/Amyotrophic Lateral Sclerosis (MND/ALS), identify potential mechanistic pathways through which athletic exposures may influence disease risk and highlight gaps informing future research priorities.

DESIGN: Scoping Review. Online databases were used to retrieve data from available sources to 25 September 2025.

DATA SOURCES: Published and grey literature in English were identified through searches of ProQuest Central, Web of Science, Scopus, Sport Discus and PubMed. Studies were deemed eligible if they examined MND/ALS in the context of sport-related physical trauma.

METHODS: The scoping review was carried out in accordance with Preferred Reporting Items for Systematic reviews and Meta-analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. A three-step search strategy identified primary studies, secondary literature and grey literature. Following screening, data were extracted using a standardised charting tool to develop a descriptive analysis and thematic synthesis.

RESULTS: The search identified 3307 records, with 45 studies meeting inclusion criteria. General physical activity does not elevate MND/ALS risk; however, professional participation in high-impact sports, particularly those involving repetitive head impacts, has been associated with a 4-15-fold increased risk of MND/ALS. However, current evidence is largely descriptive, correlative and lacks mechanistic insights to verify causation.

CONCLUSION: This scoping review highlights a plausible association between repeated physical trauma in sport and MND/ALS, particularly in professional sports with high exposure to repeated head impacts. Future research should identify biological mechanisms linking trauma exposure with MND/ALS, integrating biomarker, experimental and longitudinal study designs to clarify causal mechanisms and inform risk mitigation in sport.},
}

@article {pmid42135109,
year = {2026},
author = {Yin, X and Zhang, H and Zhang, R and Xue, J and Hou, Y},
title = {Epigenetic noise in the aging brain: tuning neuronal vulnerability to neurodegeneration.},
journal = {Trends in neurosciences},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tins.2026.04.006},
pmid = {42135109},
issn = {1878-108X},
abstract = {Aging is the predominant risk factor for neurodegenerative diseases, yet the mechanisms linking biological aging to selective neuronal degeneration remain incompletely understood. Accumulating evidence indicates that aging progressively disrupts epigenetic regulation, manifested as increased epigenetic noise in DNA methylation, histone modifications, and chromatin accessibility, which undermines transcriptional precision and the stability of neuronal identity. Recent advances in single-cell and spatial epigenomics further suggest that these age-associated epigenetic alterations are not merely correlative but can actively shape neuronal vulnerability across brain regions and cell types. In this review, we synthesize emerging evidence showing how epigenetic noise contributes to selective neurodegeneration across Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease, and discuss emerging strategies aimed at stabilizing the aging neuronal epigenome.},
}

@article {pmid42135512,
year = {2026},
author = {Zhang, Z and van Olst, L and Alessandrini, F and Wright, M and Edwards, AJ and Boles, J and Nalbandian, A and Forsyth, AV and Shepard, N and Watson, T and Kaspi, E and Mittal, A and Kuruvilla, J and Piehl, N and Ramakrishnan, A and Appel, S and Kiskinis, E and Gate, D},
title = {Integrated single-cell and spatial transcriptomic profiling in ALS uncovers peripheral-to-central immune infiltration and reprogramming.},
journal = {Nature neuroscience},
volume = {},
number = {},
pages = {},
pmid = {42135512},
issn = {1546-1726},
support = {R01AG078713//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder marked by progressive motor neuron (MN) degeneration in the brain and spinal cord. Although neuroinflammation is increasingly recognized as a hallmark of ALS, the precise molecular programs linking immune responses to MN pathology remain poorly defined. Using an integrated approach that combines single-cell and bulk RNA sequencing with spatial proteogenomics, we characterized both shared and distinct immune dynamics in peripheral blood and spinal cord tissues from patients with sporadic ALS and those carrying C9orf72 repeat expansions. Our analysis revealed broad immune remodeling in C9orf72 ALS, ALS subtype-specific and progression-associated differences in monocyte activation and antigen-experienced CD8 effector memory T cells with clonal features consistent with antigen-driven responses. Spatial mapping revealed complement activation and lipid-programmed myeloid states converging at sites of MN loss and TDP-43 pathology. Together, these findings connect peripheral and central immune alterations to ALS heterogeneity and highlight stratified immunomodulation as a potential therapeutic strategy.},
}

@article {pmid42135750,
year = {2026},
author = {Tamaki, Y and Kaneko, S and Urushitani, M},
title = {Maintenance and disruption of the physiological dimer structure of TDP-43 in amyotrophic lateral sclerosis and frontotemporal lobar degeneration.},
journal = {BMC medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12916-026-04935-4},
pmid = {42135750},
issn = {1741-7015},
support = {24K18702//Japan Society for the Promotion of Science/ ; 23K24211//Japan Society for the Promotion of Science/ ; 25wm0625522h0001//Japan Agency for Medical Research and Development/ ; },
abstract = {BACKGROUND: Transactive response DNA-binding protein of 43 kDa (TDP-43) is an essential regulator of RNA metabolism, playing a pivotal role in splicing, transport, and stability. While its cytoplasmic aggregation is the pathological hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), recent evidence suggests that the earliest pathogenic event is the disruption of its physiological homodimeric structure. Under healthy conditions, TDP-43 forms dimers via its N-terminal domain, a configuration that is crucial for its nuclear solubility and cooperative RNA binding. In this review, we propose the "Molecular Zipper" hypothesis to describe the maintenance of TDP-43 structural homeostasis. In this framework, the N-terminal domain acts as a stabilizing "NTD-mediated anchor" that keeps the protein in a functional, "zipped" dimeric state, effectively sequestering its aggregation-prone C-terminal regions. Pathogenic triggers-including genetic mutations, aberrant post-translational modifications such as phosphorylation and acetylation, and environmental stressors-can "unzip" this structure, leading to the formation of pathogenic monomers. These pathogenic monomers show increased propensity for cytoplasmic mislocalization and recruit wild-type protein into aggregates through a prion-like seeded aggregation mechanism, culminating in nuclear functional loss and cytoplasmic gain-of-toxicity. We further evaluate the emerging diagnostic landscape, focusing on methods to monitor the dimer-to-monomer ratio.

SHORT CONCLUSION: Integrating prior biochemical data on TDP-43 dimerization with structural modeling enables a more coherent account of the transition from the physiological dimer to pathological conformers. The Molecular Zipper framework offers a conceptual foundation for reconciling existing experimental findings and for guiding future studies on early structural changes in TDP-43 proteinopathy.},
}

@article {pmid42135847,
year = {2026},
author = {Sinha, IR and Atkinson, AL and Irwin, KE and Ling, JP and Wong, PC},
title = {TDP-43: [GU]-ardian of the transcriptome.},
journal = {Molecular neurodegeneration},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13024-026-00944-2},
pmid = {42135847},
issn = {1750-1326},
abstract = {TDP-43 is a ubiquitously expressed, primarily nuclear DNA/RNA-binding protein implicated in neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's disease (AD). In this review, we examine the structure and regulation of TDP-43, how these features influence its localization and functional activity, and how their disruption may contribute to disease. Among TDP-43's diverse functions, splicing repression of nonconserved RNA sequences termed cryptic exons has emerged as especially central to human disease. TDP-43 nuclear depletion and cytoplasmic aggregation are well-established pathological features in affected neurons and glia of neurodegenerative diseases, and accumulating evidence suggests that loss of TDP-43-mediated splicing repression occurs presymptomatically in disease. Advances in RNA-sequencing have enabled systematic identification of cryptic exon inclusion as a sensitive marker of TDP-43 dysfunction. Here, we synthesize current knowledge of TDP-43 biology and curate datasets from human tissues and experimental models, focusing on cryptic splicing to provide a resource for leveraging cryptic exon biology to better understand, detect, and target TDP-43 dysfunction.},
}

@article {pmid42135897,
year = {2026},
author = {Kawazoe, T and Sugaya, K and Hayashi, K and Hino, K and Nakata, Y and Bokuda, K and Shimizu, T and Takahashi, K},
title = {Sex-Stratified Association of Regional Dopamine Transporter Binding With Disease Progression in Amyotrophic Lateral Sclerosis.},
journal = {Annals of clinical and translational neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/acn3.70432},
pmid = {42135897},
issn = {2328-9503},
support = {R051201013//Tokyo Metropolitan Hospital Organization/ ; },
abstract = {OBJECTIVE: To clarify the clinical relevance of dopamine transporter single-photon emission computed tomography (DAT-SPECT) abnormalities in amyotrophic lateral sclerosis (ALS), with a prespecified focus on sex-stratified associations with disease progression and short-term prognosis.

METHODS: Fifty-eight consecutive patients with ALS were prospectively enrolled and underwent [123]I-ioflupane DAT-SPECT, and DAT-SPECT data from 30 patients with essential tremor were analyzed as a reference group. We quantified the specific binding ratio (SBR) and the caudate-to-putamen binding ratio (BR-C/P) as age-adjusted Z-scores. Associations with functional decline (ΔALSFRS-R), respiratory function (forced vital capacity), neuropsychiatric measures, and a 6-month composite endpoint of death or ventilator support were examined using correlation and logistic regression analyses, with prespecified sex-stratified evaluation.

RESULTS: A significant sex difference in BR-C/P Z-scores prompted sex-stratified analyses. SBR Z-scores were not associated with clinical or neuropsychiatric variables in either sex. In women, lower BR-C/P Z-scores correlated with faster functional decline and were independently associated with a higher risk of death or ventilator support within 6 months (odds ratio per 1-unit increase, 0.31; 95% confidence interval, 0.12-0.83). In men, BR-C/P Z-scores correlated with forced vital capacity and respiratory decline. Exploratory voxel-based morphometry suggested limbic and striatal gray matter correlates in women with lower BR-C/P Z-scores.

INTERPRETATION: Regional dopaminergic imbalance captured by BR-C/P, rather than global SBR, demonstrated sex-stratified associations with disease progression in ALS. These findings support sex-specific interpretation of dopaminergic imaging biomarkers and suggest that BR-C/P may complement clinical measures for identifying higher-risk trajectories, particularly in women. Validation in larger, longitudinal cohorts is required.},
}

@article {pmid42135919,
year = {2026},
author = {Baird, LA and McQuown, H and Park, J and Teener, SJ and Webber-Davis, IF and Carter, AD and Jang, DG and Feldman, EL and Goutman, SA and Murdock, BJ},
title = {Peripheral Neutrophil Activation and Extracellular Trap Formation in Amyotrophic Lateral Sclerosis.},
journal = {Annals of clinical and translational neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/acn3.70431},
pmid = {42135919},
issn = {2328-9503},
support = {R01TS000339/ACL/ACL HHS/United States ; U01TS000351/ACL/ACL HHS/United States ; F31NS139629/NH/NIH HHS/United States ; R01ES030049/NH/NIH HHS/United States ; R01NS120926/NH/NIH HHS/United States ; R01NS127188/NH/NIH HHS/United States ; T32AI007413/NH/NIH HHS/United States ; //Richard Stravitz Foundation/ ; //Peter R. Clark Fund for ALS Research/ ; //Coleman Therapeutic Discovery Fund/ ; //Stanford Morris ALS Research Fund/ ; //Michael R. Johns Fund/ ; //Robert A. Epstein and Joan M. Chernoff-Epstein Emerging Scholar Fund/ ; //NeuroNetwork for Emerging Therapies/ ; //Scott Pranger ALS Center, the Dr. Randall Whitcomb Fund for ALS Genetics, the Coleman Therapeutic Discovery Fund, James and Margaret Hiller, Eric and Linda Novak/ ; },
abstract = {OBJECTIVES: Peripheral neutrophil levels in amyotrophic lateral sclerosis (ALS) inversely correlate with survival, suggesting a role for neutrophils in disease progression. Here, we characterize markers of several neutrophil activation pathways and evaluate their associations with survival to identify potential mechanisms of disease.

METHODS: Blood samples were obtained from participants at the University of Michigan ALS Clinic or from healthy controls. Ex vivo neutrophil extracellular trap (NET) formation was quantified via image analysis of primary neutrophils. Neutrophil function markers of general activation (calprotectin), migration (matrix-metalloproteinase 9 [MMP9]), and degranulation (neutrophil gelatinase-associated lipocalin [NGAL]) were then quantified in plasma via ELISA; NET formation (double-stranded DNA [dsDNA]) was assessed via fluorescence assay. These markers were then associated with ALS survival using Cox proportional hazard regression models, and analyses were stratified by sex.

RESULTS: Spontaneous ex vivo NET formation (N = 20 controls, 66 ALS) was increased in ALS (1.0% vs. 9.7%; p = 0.017). In plasma (N = 233 controls, 178 ALS), calprotectin (294 vs. 372 ng/mL; p < 0.001), MMP9 (106 vs. 152 ng/mL; p < 0.001), and NGAL (61 vs. 66 ng/mL; p = 0.01) were elevated in ALS. Calprotectin, MMP9, and NGAL levels were not associated with ALS survival; however, dsDNA was associated with poorer ALS survival but only in females (HR = 1.77 [95% CI, 1.20-2.61]; p = 0.004).

INTERPRETATION: Neutrophil function is altered in ALS, and NET formation is a potential mechanism by which neutrophils contribute to ALS, particularly in females.},
}

@article {pmid42136278,
year = {2026},
author = {Sharma, A and Mittal, V and Sharma, D and Deswal, G and Das, A and Guarve, K and Grewal, AS},
title = {Therapeutic Insights into Natural Products for Modulating Neurodegenerative Disease Pathways.},
journal = {Central nervous system agents in medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715249405308251210104405},
pmid = {42136278},
issn = {1875-6166},
abstract = {INTRODUCTION: Neurodegenerative Disorders (NDs), such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic Lateral Sclerosis (ALS), are chronic and progressive conditions marked by the gradual loss of neuronal structure and function. These disorders lead to cognitive, motor, and sensory decline, significantly reducing quality of life and posing a major global health burden due to rising healthcare costs and the absence of curative therapies. This review aims to comprehensively explore the therapeutic potential of natural products in targeting cellular and molecular mechanisms underlying NDs, highlighting their neuroprotective roles and potential for disease modification.

METHODS: A comprehensive literature review was conducted using databases including PubMed, Scopus, Web of Science, and Google Scholar. Peer-reviewed articles, clinical trials, and experimental studies were analyzed to evaluate the therapeutic potential of natural products and their bioactive compounds in the management of NDs.

RESULTS: ND pathogenesis involves oxidative stress, neuroinflammation, mitochondrial dysfunction, and abnormal protein aggregation, ultimately leading to neuronal death. Current therapies largely provide symptomatic relief without altering disease progression. Natural products from plants, fungi, and marine sources demonstrate strong neuroprotective potential through multitargeted mechanisms. Bioactive compounds such as flavonoids, alkaloids, terpenoids, and polyphenols exhibit antioxidant, anti-inflammatory, anti-apoptotic, and neuroprotective activities. Key molecules, including curcumin, resveratrol, luteolin, quercetin, and catechins, modulate signaling pathways such as NF-κB, MAPK, PI3K/AKT, Nrf2, apoptosis, and autophagy, thereby reducing amyloid-beta aggregation, protecting dopaminergic neurons, improving mitochondrial function, and enhancing cognition in preclinical and clinical studies.

DISCUSSION: Natural products represent promising candidates for disease modification in NDs due to their multi-pathway actions and relatively low toxicity. However, major limitations, such as poor bioavailability, pharmacokinetic variability, and the lack of standardized formulations, hinder clinical translation. Innovative strategies, including advanced drug-delivery systems, structural modifications, and synergistic formulations, are needed to overcome these barriers.

CONCLUSION: Natural products hold significant therapeutic potential in managing neurodegenerative diseases by targeting multiple pathological mechanisms. Their integration into ND treatment could provide safer and more effective alternatives, but further well-designed clinical trials are essential to establish their efficacy and facilitate clinical application.},
}

@article {pmid42136293,
year = {2026},
author = {Ramesh, J and Jayanthi, B and Mohan, VK and Srinivasan, S and Vijayalakshmi, MK and Mohan, M},
title = {Targeted Nanotechnology Approaches to Bypass the Blood-brain Barrier in Neurodegenerative Disorders.},
journal = {CNS & neurological disorders drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715273444679260416064255},
pmid = {42136293},
issn = {1996-3181},
abstract = {Neurodegenerative diseases like Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS), and Huntington's disease (HD) are a growing health burden across the world because of the progressive loss of brain cells and the ineffective nature of the available treatment. One significant challenge in the treatment of these conditions is the Blood- -Brain Barrier (BBB), a highly selective interface that limits the access of most therapeutic molecules to the central nervous system. Nanotechnology has become an attractive approach to addressing this difficulty, as it enables the delivery of drugs with high accuracy and actively engages in the repair of the BBB. This review provides an overall synthesis of focused nanotechnology solutions aimed at both circumventing and restoring BBB function in neurodegenerative illnesses. It discusses various nanoparticle (NP) platforms such as polymeric, lipid-based, micellar, metallic, and carbon-derived systems in the light of their physicochemical aspects, transport across the BBB, and therapeutic efficacy. Particular emphasis is put on the receptor-mediated transcytosis, neurovascular unit modulations, and the regulation of Wnt, Shh, and Tie-2 signalling pathways, which are BBB integrity pathways. The review incorporates mechanisms of BBB repair in combination with neuroprotective nanotherapies, rather than focusing solely on end repair. This review covers the role of targeted nanotechnology in the future of therapeutic approaches for neurodegenerative diseases. By connecting materials science, molecular neuroscience, and clinical innovation, it demonstrates how next-generation brain-targeted therapies can be developed using targeted nanotechnology.},
}

@article {pmid42136304,
year = {2026},
author = {Anjukandan, A and Kaliyaperumal, R},
title = {Challenges in Brain Drug Delivery for Neurodegenerative Disorders and Recent Trends: A Review.},
journal = {CNS & neurological disorders drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715273453002260416115852},
pmid = {42136304},
issn = {1996-3181},
abstract = {INTRODUCTION: Age-related disorders known as neurodegenerative illnesses are defined by uncontrolled neuronal loss that gradually impairs brain function. The majority of age-related neurodegenerative disorders are caused by dementias, in particular. Nowadays, the neurodegenerative disorders are not limited to age and are reported in all age groups. The drug delivery to treat the neurodegenerative disorders is challenging due to the presence of the blood-brain barrier (BBB).

METHOD: A critical literature review has been conducted across databases such as Scopus, Embase, Cochrane, and PubMed. Blood-brain barrier, neurodegenerative disorders, novel drug delivery system, and targeted drug therapy were the search terms.

RESULTS: Neurodegenerative Diseases (NDD) impact the peripheral nervous system, nerve cells, muscles, and the nerve-muscle junction. This term broadly encompasses cognitive disorders, such as Alzheimer's disease, Lewy body dementia, frontotemporal dementia, and vascular dementia. Additionally, other neurodegenerative conditions such as multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, and spinocerebellar ataxias predominantly impair motor system function and nerves in the limbs. The existing therapeutic approaches to treat neurological diseases exhibit limited efficacy due to the BBB. This highly selective semipermeable membrane permits vital nutrients to enter the brain while blocking the potentially harmful toxins. It makes it very challenging to get medications into the brain. There are several effective approaches to deliver drugs to the brain (nanocarrier systems, intranasal administration, and focused ultrasound) to address the limitations of conventional treatments.

CONCLUSION: This review discusses neurodegenerative disorders, brain anatomy/physiology, barriers to drug delivery, and strategies to overcome these limitations.},
}

@article {pmid42136825,
year = {2026},
author = {Pan, J and Zhang, C and Li, J and Ma, L},
title = {Neurocritical progression in amyotrophic lateral sclerosis: pathological relevance and validation.},
journal = {Open life sciences},
volume = {21},
number = {1},
pages = {20251323},
pmid = {42136825},
issn = {2391-5412},
abstract = {Evidence from multiple clinical studies indicates that amyotrophic lateral sclerosis (ALS) frequently evolves into a condition requiring neurocritical care. In advanced stages or during acute complications, ALS can rapidly transition into a neurocritical state characterized by respiratory insufficiency, systemic dysfunction, and accelerated neurological decline. Although current management strategies for advanced-stage ALS are relatively well established, there remains a significant lack of targeted interventions aimed at preventing or attenuating neurocritical deterioration. This review systematically examines the pathophysiological mechanisms underlying neurocritical progression in ALS, including respiratory failure, metabolic imbalance, autonomic dysfunction, and multisystem involvement. We further evaluate emerging and potential therapeutic strategies designed to mitigate disease severity and stabilize critical neurological function. In addition, we analyze clinical and biological factors that increase susceptibility to neurocritical states and discuss evidence-based approaches to delay disease progression. By integrating clinical observations with mechanistic insights, this review aims to improve early recognition, optimize neurocritical management, and ultimately enhance outcomes for patients with ALS.},
}

@article {pmid42137032,
year = {2026},
author = {Miura, K and Nishimura, H and Ito, Y},
title = {Enhanced saccharification yields from rice straw by senescence-induced expression of a cytokinin biosynthesis gene in intragenic rice plants.},
journal = {Plant biotechnology (Tokyo, Japan)},
volume = {43},
number = {1},
pages = {145-149},
pmid = {42137032},
issn = {1342-4580},
abstract = {Controlling the digestibility of cellulosic biomass is important for its efficient use. We generated intragenic rice plants showing enhanced saccharification yield of rice straw. The rice cytokinin biosynthesis gene, LONELY GUY, under the control of the rice senescence-inducible STAY GREEN promoter, was introduced into the rice genome via particle bombardment. The rice-derived herbicide resistance gene ALS(G95A) was used as a selection marker gene. Regenerated intragenic rice plants with no foreign sequences showed enhanced saccharification yields from the leaves at harvest, whereas no significant differences were observed at the heading stage. Because the saccharification yields of rice straw are reduced after senescence, which is suppressed by cytokinin, we propose that the enhanced saccharification yields of intragenic rice plants are caused by the delay in senescence of the rice leaves due to the expression of the introduced cytokinin biosynthesis gene upon senescence.},
}

@article {pmid42137113,
year = {2026},
author = {Rong, P and Heidrick, L},
title = {An interpretable, clinically grounded framework for digital speech biomarker development in neurodegenerative diseases.},
journal = {Frontiers in digital health},
volume = {8},
number = {},
pages = {1794169},
pmid = {42137113},
issn = {2673-253X},
abstract = {INTRODUCTION: Communication ability-a key determinant of quality of life-is frequently affected and progressively declines in neurodegenerative diseases. Effective management of progressive communication disorders requires a personalized approach to deliver timely interventions tailored to the evolving profiles of communicative impairment, thereby supporting functional communication throughout the disease course. To this end, reliable tools capable of detecting and quantifying both disease-specific patterns of communicative impairment and within-disease phenotypic variability are urgently needed. This study leverages Artificial Intelligence and advanced data analytics to develop an acoustic-based framework for automated extraction of interpretable, clinically grounded speech markers to enable objective assessment and phenotyping of progressive communication disorders.

METHODS: Three groups of participants, including 14 individuals with amyotrophic lateral sclerosis (ALS) and 15 individuals with Parkinson's disease (PD), alongside 10 neurologically healthy controls, performed a standardized oral passage reading task, yielding 739 speech samples. Fifty acoustic features were extracted using an automated analytic pipeline and subsequently clustered into six interpretable composite markers. The clinical utility of these markers was evaluated with the recorded speech samples by examining their (1) associations with standardized metrics of cognitive, motor speech, and overall communicative functions, (2) efficacy for detecting and differentiating disease-specific communicative impairment patterns in ALS and PD using supervised machine learning, and (3) utility for within-disease phenotyping and stratification using unsupervised clustering analysis.

RESULTS: The markers effectively (1) detected subtle subclinical changes across multiple domains prior to substantial declines in functional communication outcomes; (2) differentiated disease-specific patterns of communicative impairment (multiclass area under the curve > 0.90); and (3) identified subgroups with distinct speech profiles within each disease.

DISCUSSION: The findings support the potential of the proposed framework as a clinically translatable, objective tool to facilitate early detection, differential diagnosis, and phenotyping of progressive communication disorders, ultimately advancing personalized, measurement-based care in neurodegenerative diseases.},
}

@article {pmid42139128,
year = {2026},
author = {Hong, J and Rao, P and Wang, W and Najafizadeh, L},
title = {EMBC Special Issue: ChatBCI-Assist: An Intent-Based P300 Speller with A Locally-Deployed LLM and Adaptive Stopping Strategy Enabling Record Online Spelling Performance.},
journal = {IEEE transactions on bio-medical engineering},
volume = {PP},
number = {},
pages = {},
doi = {10.1109/TBME.2026.3693965},
pmid = {42139128},
issn = {1558-2531},
abstract = {P300-based speller brain computer interfaces (BCIs) provide promising communication solutions for individuals with severe motor impairments such as those with amyotrophic lateral sclerosis (ALS). However, existing P300 spellers are constrained by slow typing speed and limited efficiency. Here, we present ChatBCI-Assist, an intent-based P300 speller that integrates a locally-deployed large language model (LLM), fine-tuned for the task at hand, with an adaptive stopping strategy for key selection and a graphical user interface (GUI) designed for efficient message composition, to achieve record-level online spelling performance. The LLM, trained on an ALS-specific communication corpus using low-rank adaptation (LoRA), produces context-aware, semantically coherent, and prefix-constrained word and phrase predictions in real time. The proposed GUI supports efficient, user-adaptive message composition, while the adaptive stopping strategy dynamically adjusts stimulus presentation based on each subject's classification performance. Combined with a subject specific stepwise linear discriminant analysis (SWLDA) classifier, ChatBCI-Assist enhances spelling efficiency. Results from online experiments demonstrate that ChatBCI-Assist achieves record performance, with an average information transfer rate (ITR) of 105.2 bits/min, an overall character-level mutual information rate (MIR) of 52.9 bits/min and characters per minute (CPM) of 19.7 in copy-spelling tasks, and 30.7 CPM in semantic spelling tasks. Evaluated using semantic ITR (SITR), a metric proposed to characterize semantic communication efficiency, ChatBCI-Assist achieved SITR of 147.1 bits/min. User experience evaluations further confirm reduced workload and higher usability from LLM-based semantic spelling configurations, compared to traditional copy-spelling paradigms (dictionary or LLM). This work demonstrates that integrating locally-adapted LLMs with intent driven design and subject-specific decoding optimization can substantially improve the speed, efficiency, and user experience of BCI-based communication systems.},
}

@article {pmid41922953,
year = {2026},
author = {Xing, Z and Cheng, Z and Yang, X and Hu, L and Wang, K and Wang, Y and Hu, D and Wang, YH and Du, J and Wang, L and Li, J},
title = {Integrated genomic and transcriptomic analysis reveals candidate genes underlying herbicide resistance in Sorghum.},
journal = {BMC plant biology},
volume = {26},
number = {1},
pages = {},
pmid = {41922953},
issn = {1471-2229},
support = {32372134//The National Natural Science Foundation of China/ ; },
abstract = {BACKGROUND: Herbicide-resistant germplasms provide critical genetic resources for improving weed control and understanding resistance mechanisms in crops.

OBJECTIVE: To screen sorghum accessions for tolerance to ACCase and ALS inhibitor herbicides at the seedling stage, identify the major locus and strong candidate gene associated with feproxydim resistance, and verify the gene expression pattern and genetic variation by quantitative real‑time PCR (qRT‑PCR) and KASP genotyping.

METHOD: A total of 316 sorghum accessions were screened for seedling-stage herbicide tolerance using gradient herbicide treatments. Bulked segregant analysis sequencing (BSA-Seq) was performed on resistant and susceptible gene pools constructed from the F₂ population derived from IS1219 × RTx430. Transcriptome sequencing (RNA-Seq) was conducted on leaf tissues after feproxydim treatment to identify candidate genes within the mapped interval. KASP markers were developed for the functional variation site of the key candidate gene for genotyping validation. Quantitative real‑time PCR (qRT-PCR) was used to measure the relative expression level of the target gene and compare it with the susceptible control line. Protein sequence comparison was used to detect variations in the key candidate gene between resistant and susceptible lines.

RESULT: In the screening with the ACCase inhibitor 10% feproxydim, IS1219 exhibited high-level resistance. Preliminary screening under the ALS inhibitor mesosulfuron-methyl treatment identified only SJ304 with visible tolerance, which was not subjected to further mapping or validation. BSA-Seq identified a major feproxydim resistance QTL on chromosome 1. RNA-Seq revealed five co-expressed candidate genes in the target interval, among which Sobic.001G431500 (encoding carboxylesterase 17, an α/β‑hydrolase) was markedly upregulated in the resistant line IS1219 but not in the susceptible line RTx430. Quantitative real‑time PCR (qRT-PCR) analysis confirmed that Sobic.001G431500 was significantly upregulated in the resistant line IS1219 compared with the susceptible control. KASP genotyping demonstrated that the IS1219 allele cosegregated with feproxydim resistance. Protein sequence comparison showed that the IS1219 allele carried a missense mutation V300A and a deletion P301_P303 at and after position 300.

CONCLUSION: These findings identify a major QTL and a strong candidate gene Sobic.001G431500 associated with feproxydim resistance in the sorghum line IS1219, based on differential expression, genetic variation, and genotype–phenotype cosegregation. This study provides valuable genetic resources and functional markers for marker-assisted selection and breeding of feproxydim-tolerant sorghum varieties.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12870-026-08624-5.},
}

@article {pmid42126073,
year = {2026},
author = {Razlan, AN and Ma, W and Dickie, AC and Polgar, E and McFarlane, AG and Yadav, M and Cooper, AH and Strathdee, D and Watanabe, M and Bell, AM and Todd, AJ and Hachisuka, J},
title = {Characterisation of cold-selective lamina I spinal projection neurons in the mouse.},
journal = {eLife},
volume = {14},
number = {},
pages = {},
pmid = {42126073},
issn = {2050-084X},
support = {10.35802/219433/WT_/Wellcome Trust/United Kingdom ; MR/V033638/1/MRC_/Medical Research Council/United Kingdom ; 10.35802/304005/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Animals ; Mice ; *Cold Temperature ; TRPM Cation Channels/metabolism/genetics ; *Neurons/physiology ; Optogenetics ; Calbindins/metabolism ; Mice, Inbred C57BL ; *Spinal Cord/physiology/cytology ; Male ; },
abstract = {Skin cooling is detected by primary afferents that express the Trpm8 channel, but how this information is conveyed to the brain remains poorly understood. We have previously identified a population of lamina I projection neurons belonging to the anterolateral system (ALS) that receive numerous contacts from Trpm8-expressing primary afferents. Here, using a semi-intact somatosensory preparation, we provide evidence that these cells correspond to the cold-selective ALS neurons identified in previous physiological studies. We also confirm the presence of synapses from Trpm8 afferents onto these cells at the ultrastructural level and with optogenetics. Based on our previous transcriptomic findings, we identify calbindin as a molecular marker, and show that this can be used to target the cold-selective ALS neurons for anterograde tracing studies. We provide evidence that they project to brain regions that have been implicated in thermosensation: the rostralmost part of the lateral parabrachial area, the caudal part of the periaqueductal grey matter, and the posterior triangular and ventral posterolateral nuclei of the thalamus. Our findings provide important insights into the organisation of neuronal circuits that underlie thermoregulation and the perception of cold stimuli applied to the skin.},
}

Animals
Mice
*Cold Temperature
TRPM Cation Channels/metabolism/genetics
*Neurons/physiology
Optogenetics
Calbindins/metabolism
Mice, Inbred C57BL
*Spinal Cord/physiology/cytology
Male

@article {pmid42127155,
year = {2026},
author = {Sunindyo, WD and Anshori, I and Wiguna, KA and Kahari, MMH and Syafalni, I and Dwiyanti, L and , },
title = {Algorithm-assisted interpretation of cyclic and differential pulse voltammetry for cardiac troponin detection.},
journal = {PloS one},
volume = {21},
number = {5},
pages = {e0348348},
doi = {10.1371/journal.pone.0348348},
pmid = {42127155},
issn = {1932-6203},
mesh = {*Algorithms ; Humans ; *Electrochemical Techniques/methods ; Biomarkers/blood ; Electrodes ; Biosensing Techniques/methods ; *Troponin/analysis ; Reproducibility of Results ; },
abstract = {Cardiovascular disease remains a leading cause of mortality worldwide, and rapid identification of cardiac biomarkers is essential for early detection. Electrochemical voltammetry techniques, particularly cyclic voltammetry (CV) and differential pulse voltammetry (DPV), are widely used for detecting cardiac troponin; however, interpretation of raw voltammetric signals is often affected by baseline drift, signal noise, and operator-dependent analysis. This study proposes an algorithm-assisted analytical framework for automated interpretation of voltammetric data obtained from a screen-printed carbon electrode potentiostat. Polynomial fitting was applied for baseline correction in CV signals, while asymmetric least squares (ALS) was employed for DPV data. Peak-to-baseline current response was extracted as a quantitative indicator of biomarker presence. The proposed method successfully identified characteristic voltammetric peaks and distinguished samples with higher and lower cardiac biomarker responses relative to a predefined detection threshold. The analysis showed close agreement with reference electrochemical analysis software, demonstrating reliable peak detection and baseline estimation. By reducing manual interpretation and improving signal clarity, the framework enhances the reproducibility and accessibility of electrochemical biosensor measurements and supports early screening of cardiac biomarkers.},
}

*Algorithms
Humans
*Electrochemical Techniques/methods
Biomarkers/blood
Electrodes
Biosensing Techniques/methods
*Troponin/analysis
Reproducibility of Results

@article {pmid42127907,
year = {2026},
author = {Xu, W and Li, H and Zhang, W and Bai, G and Shen, C and Zhang, K},
title = {S-acylation of TDP43 regulates its condensation in amyotrophic lateral sclerosis.},
journal = {Molecular cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.molcel.2026.04.016},
pmid = {42127907},
issn = {1097-4164},
abstract = {TDP43 inclusion bodies are widely present in the majority of patients with familial and sporadic amyotrophic lateral sclerosis (ALS). The mechanisms regulating TDP43 solubility remain incompletely understood. Here, we report that TDP43 undergoes S-acylation primarily at the Cys244 residue by the S-acyltransferase zDHHC23. This S-acylation maintains the liquid-like properties of TDP43 by reducing the aberrant interaction with poly(ADP-ribose) polymerase 1 (PARP1) and PARylated proteins, thereby countering the pathological condensation of TDP43. S-acylation-deficient TDP43 inclusions sequester the translational machinery and inhibit cytoplasmic protein translation, ultimately resulting in neurotoxicity. Importantly, TDP43 S-acylation is decreased in the familial ALS-associated TDP43 mutants as well as in SOD1-G93A mice and C9orf72-ALS induced pluripotent stem cell (iPSC)-derived neurons, suggesting the widespread involvement of TDP43 S-acylation in ALS pathogenesis. Our findings reveal an undescribed modification of TDP43 and provide deeper insight into the regulation of TDP43 pathological condensation in ALS.},
}

@article {pmid42129145,
year = {2026},
author = {Pulst, SM and Paul, S and Nguyen, H and Dansithong, W and Figueroa, KP and Gandelman, M and Bonini, NM and Scoles, DR},
title = {A human Staufen1 BAC transgenic mouse exhibits abnormal autophagy and neurodegeneration across the central nervous system.},
journal = {Cell death & disease},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41419-026-08830-x},
pmid = {42129145},
issn = {2041-4889},
support = {R21NS127028//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R01NS137233//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R01NS097903//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R21NS128630//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R61/R33NS124965//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R21NS128630//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R35NS097275//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R56NS033123//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R37NS033123//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R35NS127253//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; R61/R33NS124965//U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; },
abstract = {RNA-binding proteins (RBPs) play an essential role in development, normal functioning, and human disease. Staufen1 (STAU1) is an RBP that regulates mRNA degradation and subcellular localization, and is part of the ATXN2 protein complex. Previously, we showed that STAU1 is overabundant in patient fibroblasts and in mouse models of Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and spinocerebellar ataxia type 2 (SCA2), where it is associated with impaired autophagic flux due to STAU1-mediated upregulation of mTOR translation. STAU1 overabundance and impaired autophagy cause accumulation of biomolecular condensates and abnormal unfolded protein response (UPR). We generated a mouse model expressing the entire human STAU1 gene (hSTAU1) in a bacterial artificial chromosome (BAC) construct. hSTAU1 in these mice was expressed in cerebral hemispheres, cerebellum, and spinal cord, as well as cultured cortical neurons and cortical and spinal cord astrocytes, and microglia. Expression of hSTAU1 caused dysregulated gene expression, abnormal autophagy, glial activation, and changes in neuronal marker proteins. All of these were significantly improved by reducing STAU1 abundance by RNAi, but exacerbated in BAC-STAU1 mice crossed with Prp-TDP-43(Q331K) transgenic mice. Similar results were also obtained in eye phenotypes in ALS- and SCA2-relevant fly models upon changing staufen-1 dosage. Despite the molecular changes, we observed no overt behavioral changes in mice up to 55 weeks of age, suggesting that STAU1 may function as an epistatic modifier of neuronal degeneration. The BAC-hSTAU1 mouse will be useful for developing therapies targeting the human STAU1 gene.},
}

@article {pmid42130389,
year = {2026},
author = {Thurn, T and Chiò, A and Galvin, M and Stavroulakis, T and Anneser, J},
title = {Beyond the surface: Exploring differing aspects of wishes to hasten death in patients with amyotrophic lateral sclerosis.},
journal = {Palliative & supportive care},
volume = {24},
number = {},
pages = {e147},
doi = {10.1017/S1478951526102673},
pmid = {42130389},
issn = {1478-9523},
mesh = {Humans ; Female ; Male ; *Amyotrophic Lateral Sclerosis/psychology/complications ; Cross-Sectional Studies ; Middle Aged ; Aged ; Longitudinal Studies ; Europe ; *Attitude to Death ; Quality of Life/psychology ; Surveys and Questionnaires ; Adult ; Aged, 80 and over ; },
abstract = {OBJECTIVES: This study investigates differing aspects of wishes to hasten death (WTHD) distinguished by the extent to which WTHD were linked to patients' agency: desire for hastened death (DHD), defined as general wishes for death to come sooner, and hastening death intentions (HDI), defined as thoughts about ending one's life. In particular, this study aims to examine the differences between DHD and HDI in patients with amyotrophic lateral sclerosis (pALS) and identify predictive factors for both.

METHODS: A cross-sectional nested study was conducted within a multi-center longitudinal study involving pALS from 5 European countries. Data collected included DHD (Schedule of Attitudes toward Hastened Death), HDI ("could you currently imagine ending your life?"), sociodemographic and clinical characteristics, psychological distress, quality of life, and social and spiritual-existential aspects.

RESULTS: In our sample of 121 pALS, 12.4% (15/121) expressed DHD, and 28.1% (34/121) expressed HDI. Of the 38 patients reporting any WTHD, only 11 experienced both DHD and HDI simultaneously. 23 patients reported HDI without DHD, while 4 patients expressed DHD without HDI. Multivariable logistic regression identified loneliness (OR = 1.33, 95% CI 1.03-1.71, p = 0.028) and reduced meaning in life (OR = 0.89, 95% CI 0.84-0.95, p < 0.001) as independent predictors of DHD. For HDI, independent predictors were female gender (OR = 3.31, 95% CI 1.37-7.98, p = 0.008) and lower spirituality (OR = 0.92, 95% CI 0.88-0.95, p < 0.001).

SIGNIFICANCE OF RESULTS: One in 3 pALS expressed WTHD. Our separate analysis of DHD and HDI supports the existence of distinct manifestations of WTHD and varying underlying factors. While DHD and HDI were associated with different predictors, our results point to the crucial role of spiritual-existential factors in the experience of WTHD, identifying these aspects as target points for intervention. This study highlights the importance of a nuanced understanding and communication regarding WTHD.},
}

Humans
Female
Male
*Amyotrophic Lateral Sclerosis/psychology/complications
Cross-Sectional Studies
Middle Aged
Aged
Longitudinal Studies
Europe
*Attitude to Death
Quality of Life/psychology
Surveys and Questionnaires
Adult
Aged, 80 and over

@article {pmid42131110,
year = {2026},
author = {Zhang, M and Su, L and Han, W and Song, F and Fu, Y and Chi, MB and Chen, X and Wu, YH and Gao, SJ},
title = {Single cell Raman spectroscopic profiles predict treatment responses in patients with de novo acute myeloid leukemia.},
journal = {Frontiers in cell and developmental biology},
volume = {14},
number = {},
pages = {1767226},
pmid = {42131110},
issn = {2296-634X},
abstract = {INTRODUCTION: Leukemia is a clonal malignant proliferative disease originating from hematopoietic stem cells. Although its treatment strategy has gradually developed from traditional chemotherapy to a multimodal treatment system including novel targeted therapy and immunotherapy, primary drug resistance in particular remains the core clinical problem leading to poor patient prognosis. This clinical dilemma indicates that the traditional genotyping system based on genomics has not been able to fully resolve the molecular heterogeneity of acute myeloid leukemia (AML), and it is urgent to establish a precise stratified model that can dynamically reflect the functional status of tumor cells in the initial stage of treatment.

METHODS: In this study, Raman spectroscopy (RS) combined with machine learning algorithm was used to construct a metabolic prognosis prediction model for AML chemotherapy response. Bone marrow single cell Raman spectroscopy data of newly diagnosed AML patients were collected, and the molecular fingerprint was analyzed by principal component analysis linear discriminant analysis (PCA-LDA) and multivariate curve resolute alternating least square method (MCR-ALS).

RESULTS: The results showed that the PCALDA model achieved complete remission or non-remission (CR/NR) classification through 24 principal components (cumulative variance contribution of 90.1%), the accuracy of external validation was 94.8% (sensitivity 97.9%, specificity 92.0%), and the AUC reached 96.27%. Protein, lipid, nucleic acid and mixed components were decomposed by MCR-ALS, and lipid and nucleic acid metabolic pathways were enriched in NR group (P < 0.001).

DISCUSSION: Studies have shown that RS single-cell metabolic fingerprint can decode the metabolic reprogramming features associated with chemotherapy resistance in AML, providing a new marker-free and highly sensitive tool for real-time prognostic stratification and targeted intervention.},
}

@article {pmid42131159,
year = {2026},
author = {Dewan, L and Pal, S and Tibrewal, S},
title = {Letter to the Editor: Comment on Takai et al.'s "Age-Associated Differences in Optic Disc Findings of Leber's Hereditary Optic Neuropathy".},
journal = {Neuro-ophthalmology (Aeolus Press)},
volume = {50},
number = {3},
pages = {292-293},
pmid = {42131159},
issn = {0165-8107},
abstract = {This letter comments on the study by Takai et al examining age-related differences in acute phase optic disc morphology in Leber hereditary optic neuropathy. We highlight methodological considerations in subjective fundus photograph assessment, and discuss additional factors such as refractive status and timing of presentation that may influence the presence of optic disc edema. These points may aid in refining phenotypic interpretation in future LHON studies.},
}

@article {pmid42131356,
year = {2026},
author = {Macchietti, L and Carta, M and Delogu, F and Grepioni, F and Emmerling, F and Casali, L},
title = {Scaling up mechanochemical reactions: linking crystalline phase evolution studied via in situ PXRD with kinetics from MCR-ALS.},
journal = {Chemical science},
volume = {},
number = {},
pages = {},
pmid = {42131356},
issn = {2041-6520},
abstract = {This work addresses a key challenge in scaling up mechanochemical synthesis: deriving a kinetic model when unpredictable formation and intricate interaction of multiple crystalline phases occur during solid-state transformations. Reaction kinetics translate our understanding of chemical processes into mathematical rate expressions used for reactor design and evaluation, thus representing a challenge to be addressed for the scale up at the industrial level. Choosing co-crystallization of chloro-3-sulfamoylbenzoic acid (CSBA) and isonicotinamide (INA) as a model system, at first we employ time-resolved in situ powder X-ray diffraction (PXRD) and multivariate curve resolution-Alternating Least Squares (MCR-ALS) analysis to quantify and resolve the evolution of crystalline intermediates under varying methanol-assisted conditions. Our data show that even small changes in the amount of methanol can dramatically alter the kinetic profile, stabilise transient phases (including some that were previously unreported) and alter the overall reaction pathway. We then demonstrate the robust deconvolution of overlapping phases and the extraction of quantitative rate parameters that rationalize the observed behaviour by integrating kinetic modelling as a soft-hard constraint in the MCR-ALS workflow. The validation of the established MCR-ALS workflow is achieved by applying a phenomenological kinetic modelling tailored to rationalize the mechanochemical reaction rates. These results establish a broadly applicable platform for analysing and controlling the complex phase evolution, along with the derivation of a kinetic model instrumental to mechanochemical process development and scaling up, thereby supporting the transition of sustainable solid-state syntheses from the laboratory to industry.},
}

@article {pmid42133017,
year = {2026},
author = {Svihlik, J and Rusz, J},
title = {Screening speech disorders in progressive neurological diseases via long-term average spectrum.},
journal = {Journal of neural transmission (Vienna, Austria : 1996)},
volume = {},
number = {},
pages = {},
pmid = {42133017},
issn = {1435-1463},
abstract = {The long-term averaged spectrum (LTAS) may provide a universal method for capturing distinct patterns of dysarthria. This study aimed to evaluate the sensitivity of LTAS descriptors in a broad range of neurological diseases and various types and severities of dysarthria. Four spectral moments of spectral mean, spectral standard deviation, spectral skewness and spectral kurtosis based on LTAS were computed for reading passage collected from 461 speakers, including 306 healthy controls and 155 neurological patients secondary to Parkinson's disease (PD), progressive supranuclear palsy, multiple system atrophy (MSA), Huntington's disease, essential tremor, cerebellar ataxia (CA), multiple sclerosis (MS), and amyotrophic lateral sclerosis. Compared to controls, the spectral mean was significantly lower in PD and MS while elevated in CA. Significantly changed LTAS features were observed only in hypokinetic dysarthria and in mixed dysarthrias manifesting hypokinetic elements. Although LTAS features differed between controls and patients with varying degrees of dysarthria, there was no progressive increase in dysarthria severity. Our findings suggest that LTAS-based speech analysis may provide valuable cues to aid differential diagnosis among neurological diseases with overlapping clinical features. LTAS appears more informative when applied to specific diseases than to pooled dysarthria types arising from diverse neurological etiologies.},
}

@article {pmid42134656,
year = {2026},
author = {Vassallu, F and López, M and López Ambrosioni, F and Casal, J and Caltana, L and Igaz, LM},
title = {TDP-43 expression in the cytoplasm leads to early synaptic and mitochondrial abnormalities in an inducible mouse model of ALS/FTD.},
journal = {Neurochemistry international},
volume = {},
number = {},
pages = {106180},
doi = {10.1016/j.neuint.2026.106180},
pmid = {42134656},
issn = {1872-9754},
abstract = {TDP-43 proteinopathy is the primary pathology associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), indicating that these neurodegenerative diseases have common underlying mechanisms. We have previously shown that transgenic (Tg) mice conditionally overexpressing a cytoplasmic form of human TDP-43 protein (TDP-43-ΔNLS) in forebrain neurons replicate key features of FTD/ALS, including altered cognitive, motor and social behaviors. These behavioral phenotypes and changes in plasticity-related gene expression can be detected as early as 1 month after Tg induction, before overt neurodegeneration occurs. To assess early ultrastructural features in this model, we performed Transmission Electron Microscopy (TEM) analysis in the cortex (Ctx) and hippocampus (Hp) of Tg animals and their non-Tg controls. TEM evaluation of Ctx and Hp revealed that synaptic density was significantly decreased and synapse length was increased in both regions of Tg animals. Synaptic cleft thickness was increased and post-synaptic density thickness was decreased only in the Ctx of Tg mice, revealing differential regional effects in synaptic morphology. We analyzed mitochondrial density and we found an increase in the Ctx and a decrease in the Hp of Tg animals, with preserved individual mitochondrial area. Lastly, transcriptomic and proteomic analysis from both transgenic TDP-43-ΔNLS mice and human proteinopathy showed widespread decreased expression of synaptic structure and function genes. The alterations in synaptic density and architecture reported here, combined with the mRNA/protein expression data, suggest that TDP-43-ΔNLS mice may exhibit abnormal synaptic transmission and that ultrastructural changes play a role in the early behavioral deficits observed in this model.},
}

@article {pmid42134658,
year = {2026},
author = {Purushotham, SS and Chesworth, R and Keembiyage, N and Münch, G and Gyengesi, E and Buskila, Y},
title = {The impact of long-term feeding with curcuminoids phospholipids enriched diet on disease progression of fALS.},
journal = {Neurochemistry international},
volume = {},
number = {},
pages = {106183},
doi = {10.1016/j.neuint.2026.106183},
pmid = {42134658},
issn = {1872-9754},
abstract = {Amyotrophic lateral sclerosis (ALS) is a debilitating and fatal neurodegenerative disease characterised by the progressive loss of motor functions affecting both upper and lower motor neurons. Although considered multifactorial with an unclear aetiology, it is believed that the interplay between genetic and environmental factors, with neuroinflammation playing a key role in disease progression, contributes to its development. There is currently no effective treatment for ALS. Curcumin has been recently highlighted for its potential therapeutic role in treating neurodegenerative diseases. Curcumin phospholipids, a highly bioavailable form of curcumin that allow the curcumin to be absorbed into the bloodstream more effectively than standard curcumin extracts, is considered as a natural cytokine-suppressive anti-inflammatory compound (CSAID) that is well-known for its therapeutic properties and is considered safe for humans and rodents at low to moderate concentrations. In this study, we investigated whether a long-term feeding regimen incorporating curcuminoids phospholipids-enriched diet early in disease progression could mitigate motor deficits and affect the lifespan of the SOD1 mouse model of familial ALS (fALS). Our results indicate sex-differences regarding the effect of curcumin supplementation on motor deficits and anxiety-like behaviour. While long-term feeding with curcuminoids phospholipids enriched diet had a complex effect on SOD1 female mice expressed as reduced anxiety like behaviour and motor deficits at the walking beam test, it had no effect on SOD1 male mice. Moreover, curcuminoids supplementation had a limited effect on disease onset and progression in SOD1 mice model for fALS.},
}

@article {pmid42134762,
year = {2026},
author = {Song, J and Lee, S and Lee, J and Gil, Y and Kim, T and Kim, SY and Cha, SJ and Kim, HJ and Kim, K},
title = {Carboplatin alleviates astrocytic TDP-43 neurotoxicity by inhibiting NF-κB activation.},
journal = {European journal of pharmacology},
volume = {},
number = {},
pages = {178968},
doi = {10.1016/j.ejphar.2026.178968},
pmid = {42134762},
issn = {1879-0712},
abstract = {Amyotrophic lateral sclerosis (ALS) is a rare and progressive motor neuron disease; however, its exact pathogenic mechanisms remain unclear. Currently, no effective treatments are available for this disease. Therefore, in this study, we investigated the anti-inflammatory effects of the anti-cancer agent, carboplatin, on neuronal cells and its potential therapeutic effects against ALS. Carboplatin inhibited NF-κB phosphorylation in the transactive response DNA-binding protein (TDP)-43-transfected astrocytes, reducing pro-inflammatory cytokine levels, without affecting the TDP-43 protein levels. In neuron-astrocyte co-culture models, carboplatin effectively alleviated TDP-43-induced toxicity by restoring mitochondrial integrity, specifically rescuing basal respiration, ATP production, and maximal respiratory capacity. In vivo, carboplatin rescued the locomotor deficits in glial-specific TDP-43-expressing Drosophila, without altering TDP-43 protein levels and subcellular localization. These findings suggest that TDP-43-induced astrocytic damage compromises mitochondrial functions in adjacent neurons, and that carboplatin-mediated restoration of TDP-43-mediated astrocyte damage is critical for neuronal survival and functions. Therefore, carboplatin, a chemotherapeutic agent, represents as a potential therapeutic candidate for TDP-43-associated proteinopathies.},
}

@article {pmid42134826,
year = {2026},
author = {Fei, X and Qiu, C and Xiao, P and Du, H and Yang, Q},
title = {From Risk Identification to Risk Mitigation: Expanding the Utility of Ohteru Et al.'s Findings in Institutionalized Older Adults.},
journal = {Geriatrics & gerontology international},
volume = {26},
number = {5},
pages = {e70535},
doi = {10.1111/ggi.70535},
pmid = {42134826},
issn = {1447-0594},
}

@article {pmid42117777,
year = {2026},
author = {Dong, J and Yan, M and Farmer, A and Jiang, L and Zhen, J and Tong, Y and Dong, Y and Zhang, G and Wu, L and Guo, Y and Yin, X and Fang, L and Xu, Z},
title = {The Impact of Social Isolation on Treatment Burden Among Community-Dwelling Adults With Disability and Multimorbidity: A Longitudinal Qualitative Study in Urban China.},
journal = {Health expectations : an international journal of public participation in health care and health policy},
volume = {29},
number = {3},
pages = {e70693},
doi = {10.1111/hex.70693},
pmid = {42117777},
issn = {1369-7625},
support = {2024KY1026//Medical Science and Technology Project of Zhejiang Province/ ; //National Institute of Health and Care Research Oxford Biomedical Research Centre/ ; },
mesh = {Humans ; *Social Isolation/psychology ; Female ; Male ; Longitudinal Studies ; Qualitative Research ; China ; *Persons with Disabilities/psychology/statistics & numerical data ; Aged ; *Multimorbidity ; Middle Aged ; *Independent Living/psychology ; Interviews as Topic ; Urban Population ; *Cost of Illness ; Adult ; Chronic Disease ; },
abstract = {BACKGROUND: Social isolation is a critical social determinant of health that amplifies the significant treatment burden faced by community-dwelling adults with disabilities and multimorbidity. While an association between these factors is established, longitudinal evidence capturing their dynamic interplay is scarce, limiting the development of effective, equitable interventions. This study aimed to longitudinally explore how treatment burden evolves among this population and to elucidate the mechanisms through which social isolation appears to operate through these changes.

METHODS: We conducted a longitudinal qualitative study using interpretive description in Hangzhou, China. Participants were adults with physician-diagnosed disabilities and ≥ 2 chronic conditions, recruited via purposive sampling from community health centres. Each participant completed three in-depth, semi-structured interviews over 12 months. We conceptualized treatment burden using Demain et al.'s adaptation of the Cumulative Complexity Model. Data analysis was an iterative process involving constant comparison to identify key themes regarding the interplay of social isolation and treatment burden over time.

RESULTS: A total of 24 participants (13 were women; median age 67.5 years) completed the study. Our analysis revealed that social isolation was described by participants as dynamically contributing to increased treatment burden through four interconnected mechanisms: (1) Eroding autonomy, leading to passive healthcare decision-making; (2) Compromising emotional well-being, which depleted self-management capacity; (3) Straining relational networks, resulting in the loss of crucial informal support; and (4) Creating navigational barriers, which led to difficulties managing complex treatments. A key cross-cutting theme was the apparent role of depressive symptoms, which participants described as being exacerbated by isolation and, in turn, appearing to contribute to more negative illness perceptions and functional decline. This pattern was consistent with a progressive intensification of treatment burden as emotional and physical challenges fed into each other over time.

CONCLUSION: Social isolation appeared to function not merely as a passive correlate but as a factor that longitudinally contributed to greater treatment burden, thereby exacerbating health inequities for adults with disabilities and multimorbidity. This pattern appeared to be further shaped by the intersection with depressive symptoms. To mitigate this, multi-level interventions are essential. Priorities should include addressing structural barriers through policies that foster community integration, strengthening mental health support within primary care, and redesigning services to be more relationally-centred and less burdensome.

Patients, care-givers, people with lived experience or members of the public were not involved in the study design, conduct, data analysis or preparation of the manuscript. However, preliminary findings were shared and discussed with two patient advisors who had lived experience of disability and multimorbidity but were not participants in the interviews. Their feedback helped refine the presentation and contextual relevance of the themes.},
}

Humans
*Social Isolation/psychology
Female
Male
Longitudinal Studies
Qualitative Research
China
*Persons with Disabilities/psychology/statistics & numerical data
Aged
*Multimorbidity
Middle Aged
*Independent Living/psychology
Interviews as Topic
Urban Population
*Cost of Illness
Adult
Chronic Disease

@article {pmid42118126,
year = {2026},
author = {Ghiasi, S and Röder, T and Schunk, S and Parastar, H and Weller, P},
title = {Separation of Ammonia Isotopologues by Benchtop Drift Tube Ion Mobility Spectrometry and Chemometric Modeling.},
journal = {Journal of the American Society for Mass Spectrometry},
volume = {},
number = {},
pages = {},
doi = {10.1021/jasms.5c00434},
pmid = {42118126},
issn = {1879-1123},
abstract = {This research study assesses the applicability of drift tube ion mobility spectrometry (DTIMS) to resolve ammonia (NH3) from its isotopologue, ammonia-d3 (ND3). DTIMS, known for its rapid response at ambient pressure, was employed to conduct real-time analysis of gaseous samples. Two ammonia introduction methods were evaluated, evaporation of a 3 ppm(v) aqueous ammonia solution and dry gas synthesis. The study tested these methods for the mixture analysis of ammonia and examined their impact on resolution. The resolution of isotopologues and the influence of moisture in the carrier gas on separation were assessed. Individual analysis by evaporation method provided drift times of 6.03 ms for NH3 and 6.17 ms for ND3, from which reduced mobility (K0) values of 2.52 cm[2] V[-1] s[-1] and 2.46 cm[2] V[-1] s[-1] were calculated, respectively. The presence of moisture in the carrier gas was found to significantly reduce the resolution of isotopologue separation. To address this limitation and enhance signal clarity, the application of wavelet denoising was conducted, with universal thresholding based on Symlet, Daubechies, and Coiflet wavelet families systematically evaluated. The Daubechies wavelet (db9) at level 9 was identified as the optimal denoising approach. Following this, multivariate curve resolution alternating least-squares (MCR-ALS) was employed for the decomposition of the complex overlapping signals into their pure ion mobility spectra and corresponding concentration profiles over time. The integration of wavelet-based denoising and MCR-ALS offers a practical strategy for the enhancement of DTIMS performance in complex isotopologue separation, particularly for future studies focused on quantitative analysis. Future work will involve the integration of steady-state isotopic transient kinetic analysis (SSITKA) for a comprehensive kinetic framework for kinetic models.},
}

@article {pmid42118400,
year = {2026},
author = {Pi, C and Liu, Y and Jia, Z and Zhang, M and Wang, X and Zhao, H and Dong, Z and Yu, S and Liu, R},
title = {Mechanism of the N87D mutation in SOD1-atypical amyotrophic lateral sclerosis case report and literature review molecular mechanism of N87D mutation in SOD1.},
journal = {Neurogenetics},
volume = {27},
number = {1},
pages = {},
pmid = {42118400},
issn = {1364-6753},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; *Superoxide Dismutase-1/genetics/chemistry ; Molecular Dynamics Simulation ; *Mutation ; Protein Conformation ; Male ; Female ; Middle Aged ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with unclear pathogenesis. This study aimed to investigate the possible molecular mechanisms of ALS by analyzing protein structure and dynamics in a rapidly progressing ALS patient carrying the N87D mutation. A patient with the N87D mutation experienced rapid disease progression and died within one year. We reviewed all known mutations at the 87th position of the superoxide dismutase (SOD1) gene and the clinical characteristics. To investigate the molecular basis of the severe phenotype, we performed protein structure modeling and molecular dynamics (MD) simulations, and compared wild type homodimers, mutant homodimers, and heterodimers in terms of energy, residue fluctuation, number of hydrogen bonds, radius of gyration (Rg), principal component analysis (PCA), free energy landscape (FEL), the contribution of dimer interface residues, solvent-accessible surface area, and metal ion coordination. Our analysis revealed that patients with mutations at the 87th position of the SOD1 gene typically exhibited rapid disease progression. Protein structure modeling and MD simulations demonstrated that the N87D mutation significantly increased the energy and RMSF of SOD1 heterodimers compared to homodimers. Furthermore, Rg, FEL and PCA analyses showed that the heterodimers had a broader and more unstable conformational energy distribution, along with a stronger tendency for aggregation. Additionally, the N87D mutation disrupted metal ion coordination, further destabilizing the heterodimer and promoting protein misfolding. These findings suggest a potential molecular mechanism underlying ALS and support a protein structure based approach for investigating the pathogenic mechanisms of disease causing mutations.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics
*Superoxide Dismutase-1/genetics/chemistry
Molecular Dynamics Simulation
*Mutation
Protein Conformation
Male
Female
Middle Aged

@article {pmid42119241,
year = {2026},
author = {Toubasi, AA and Al-Sayegh, TN},
title = {Head injuries as a risk factor for amyotrophic lateral sclerosis: A systematic review and meta-analysis.},
journal = {Clinical neurology and neurosurgery},
volume = {267},
number = {},
pages = {109466},
doi = {10.1016/j.clineuro.2026.109466},
pmid = {42119241},
issn = {1872-6968},
abstract = {BACKGROUND: Previous studies have suggested that traumatic head injury (THI) is associated with amyotrophic lateral sclerosis (ALS). However, the evidence remains limited and inconsistent, partly due to small sample sizes.

OBJECTIVES: In this meta-analysis, we aimed to investigate the association between THI and the risk of ALS.

METHODS: We conducted a systematic review and meta-analysis of studies assessing the relationship between THI and ALS. The exposure of interest was THI, and the outcome of interest was ALS development. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used as effect measures.

RESULTS: Eighteen studies comprising 578,815 participants were included. THI was associated with an increased risk of ALS (OR = 1.47; 95% CI: 1.23-1.76). The association was consistent across studies conducted in Europe (OR = 1.60; 95% CI: 1.19-2.15) and the Americas (OR = 1.27; 95% CI: 1.12-1.43). Subgroup analysis by sex showed a significant association among males (OR = 2.27; 95% CI: 1.41-3.66) but it was less significant among females (OR = 1.30; 95% CI: 0.78-2.17). Both single (OR = 1.48; 95% CI: 1.18-1.85) and multiple THIs (OR = 1.34; 95% CI: 1.15-1.56) were associated with ALS. Funnel and doi plots demonstrated asymmetry indicating significant publication bias.

CONCLUSIONS: Our analysis demonstrated an association between THI and ALS, however the lack of dose-response relationship suggests it is less likely to be causative.},
}

@article {pmid42121359,
year = {2026},
author = {Goto, S and Singh, S and Zhu, Q and Vyas, SA and Wildsoet, C},
title = {Development of an Optical Defocus-Induced Myopia Model for Guinea Pigs Using Rigid Gas Permeable Contact Lenses.},
journal = {Eye & contact lens},
volume = {},
number = {},
pages = {},
doi = {10.1097/ICL.0000000000001279},
pmid = {42121359},
issn = {1542-233X},
support = {Loris and David Rich Postdoctoral Scholar//International Retina Research Foundation/ ; T32 EY007043/EY/NEI NIH HHS/United States ; R01 EY012392/EY/NEI NIH HHS/United States ; },
abstract = {OBJECTIVES: Guinea pigs are a widely used mammalian model for studies of myopia and early ocular growth regulation more generally. The study reported here covers the development of rigid gas permeable (RGP) contact lenses (CLs) for guinea pigs, as an alternative to spectacle lenses for imposing optical defocus, recognized as an important modulator of eye elongation in young animals.

METHODS: New Zealand pigmented guinea pigs (Cavia porcellus) were used in this study, with the RGP lens design based on developmental corneal shape profiles derived from anterior segment optical coherence tomography data collected across a range of ages, as typically encountered in such studies. The validity of this CL-based approach was examined in a follow-up study, in which the ocular effects of -10, 0, and +5 diopters [D] RGP lenses, applied as continuous monocular optical defocus treatments, were tracked over 2 weeks, with the fellow untreated eyes of experimental animals serving as contralateral controls. Pretreatment baseline spherical equivalent refractive errors (RE) and axial length (AL) of both eyes were measured, along with follow-up weekly measurements over the wearing period.

RESULTS: There were no differences in any of the ocular parameters between the three groups at baseline, while after two weeks of lens wear, there were significant differences between the -10 D group compared with 0 D and +5 D groups in both RE (P<0.001) and AL (P<0.05). Importantly, myopia was observed in all of the guinea pigs fitted with -10 D lenses, and overall, eyes fitted with -10 D lenses showed increased ALs and relative myopia compared with their fellows, while those fitted with +5 D lenses showed reduced ALs and relative hyperopia; the plano lens group fell in between (treated-fellow eyes: -10, 0, and +5 D lenses: -8.25, -1.0, and +0.5 D, and +0.16, +0.08, and -0.02 mm, respectively). Also importantly, no significant CL-related adverse ocular effects were observed.

CONCLUSIONS: This study provides proof of principle that defocusing RGP CLs are a feasible alternative to spectacle lenses for studies of eye growth regulation in young guinea pigs and experimental myopia specifically, with potential application in investigations into novel approaches for controlling myopia progression and underlying mechanisms.},
}

@article {pmid42123994,
year = {2026},
author = {Christodoulou, RC and Lorentzen, L and Eller, D and Vassiliou, E},
title = {Long-Chain Fatty Acids as Drivers of Neuroinflammation in Neurodegeneration: Mechanistic Links to Lipid Peroxidation, Ferroptosis, and Mitochondrial Dysfunction.},
journal = {Nutrients},
volume = {18},
number = {9},
pages = {},
doi = {10.3390/nu18091392},
pmid = {42123994},
issn = {2072-6643},
mesh = {*Ferroptosis ; Humans ; *Mitochondria/metabolism ; *Lipid Peroxidation ; *Neurodegenerative Diseases/metabolism ; *Fatty Acids/metabolism ; Animals ; *Neuroinflammatory Diseases/metabolism ; Reactive Oxygen Species/metabolism ; Oxidative Stress ; Lipid Metabolism ; },
abstract = {Background: Neurodegenerative diseases (NDs) are mainly considered disorders marked by severe immunometabolic imbalance, characterized by ongoing neuroinflammation and glial activation. While mitochondrial dysfunction and oxidative stress are well-known features, the upstream metabolic factors linking these pathological processes remain poorly understood. Methods: In this review, we examined recent preclinical and clinical studies exploring the connections between lipid metabolism, glial immunometabolism, and regulated cell death pathways. Our focus was on how long-chain fatty acids (LCFAs) facilitate communication among mitochondria, reactive oxygen species (ROS), and ferroptosis in Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Results: New evidence shifts LCFAs from merely being passive indicators of cellular damage to active, upstream regulators of the neuroimmune response. Existing research shows that excess LCFA intake can overload astrocytic mitochondrial oxidative phosphorylation, leading to abnormal lipid droplet buildup and reactive astrogliosis. This lipid-driven reactivity promotes microglial polarization toward a persistent pro-inflammatory state. Notably, high levels of specific LCFAs, especially arachidonic acid, increase ROS production and lipid peroxidation. This lipotoxic environment ultimately triggers ferroptosis, an iron-dependent form of cell death shared across multiple NDs. Conclusions: The harmful interaction among mitochondrial dysfunction, lipid peroxidation, and ferroptosis is driven by an imbalance in LCFA levels. Addressing current challenges, such as the complex effects of polyunsaturated fatty acid supplementation, requires advanced techniques like single-cell multi-omics and artificial intelligence. Understanding this intricate lipidomic-transcriptomic crosstalk is crucial for moving toward personalized neuroimmunometabolism and developing new treatments to prevent ferroptosis.},
}

*Ferroptosis
Humans
*Mitochondria/metabolism
*Lipid Peroxidation
*Neurodegenerative Diseases/metabolism
*Fatty Acids/metabolism
Animals
*Neuroinflammatory Diseases/metabolism
Reactive Oxygen Species/metabolism
Oxidative Stress
Lipid Metabolism

@article {pmid42124861,
year = {2026},
author = {Reddy, S},
title = {Foundation for Artificial Intelligence-Driven Democratization of Healthcare Access.},
journal = {Learning health systems},
volume = {10},
number = {},
pages = {e70093},
pmid = {42124861},
issn = {2379-6146},
abstract = {INTRODUCTION: Healthcare systems worldwide face unprecedented challenges, including escalating costs, workforce shortages, and access disparities, which threaten their sustainability. The WHO projects an 18 million healthcare worker deficit by 2030, while financial and geographical barriers prevent millions from receiving necessary care. The integration of Artificial Intelligence (AI) into healthcare delivery systems presents opportunities to transform medical service provision, accessibility, and experiences, potentially democratizing healthcare access.

METHODS: This perspective analysis employs a theoretical framework combining Levesque et al.'s patient-centered healthcare access model with AI democratization frameworks. The analysis synthesizes current evidence on AI healthcare applications and proposes an implementation framework encompassing four dimensions: accessibility, affordability, usability, and ethical regulation. The framework addresses stakeholder roles and governance mechanisms aligned with international standards including the EU's AI Act and WHO's AI ethics guidance.

RESULTS: Evidence demonstrates significant democratization potential through the implementation of AI. AI-powered platforms eliminate geographical barriers, reduce diagnostic timeframes, optimize resources, and enhance preventive care. Implementation challenges include algorithmic bias, data privacy concerns, digital divide risks, and regulatory fragmentation.

CONCLUSION: AI integration holds transformative potential for democratizing healthcare across demographic and socioeconomic boundaries. Successful implementation requires structured, ethically grounded approaches that prioritize accessibility, affordability, usability, and regulation while maintaining a human-centered care approach. The framework offers actionable guidance for healthcare professionals and policymakers on deploying AI technologies to reduce disparities. Continuous research, interdisciplinary collaboration, and robust governance are crucial to ensuring that AI advances healthcare equity while preserving patient autonomy and clinical judgment.

Patient and Public Involvement and Engagement was not appropriate for this theoretical framework and perspective analysis, as it represents a conceptual synthesis of existing literature and policy frameworks rather than primary research involving human participants. This manuscript establishes a theoretical foundation and an implementation framework for AI-driven healthcare democratization, grounded in published evidence and established models of healthcare access. The work focuses on guiding healthcare policymakers and planning professionals rather than collecting new data from patients or the public. However, the framework explicitly emphasizes the critical importance of patient advocacy organizations and community representation in AI development processes, recognizing that meaningful patient involvement will be essential during the actual implementation phases of AI healthcare technologies described in this theoretical foundation.},
}

@article {pmid42125740,
year = {2026},
author = {Tranoulis, I and Stefanakis, A and Giannoudi, M and Ioannidis, K},
title = {Basic life support and use of automated external defibrillator by dentists in Greece: a questionnaire-based cross-sectional study.},
journal = {Resuscitation plus},
volume = {29},
number = {},
pages = {101341},
pmid = {42125740},
issn = {2666-5204},
abstract = {BACKGROUND: Cardiac arrest is a leading cause of death; timely intervention with basic life support (BLS) is crucial for healthcare providers, including dentists. This study aimed to assess awareness, educational level, and knowledge regarding the application of BLS and the use of an automated external defibrillator (AED) among dentists in Greece.

METHODS: A cross-sectional survey using an online questionnaire was conducted to collect demographic data, knowledge of BLS/Advanced Life Support (ALS), and experience in managing medical emergencies in dental practices. The results were statistically analysed, with the level of significance set at P < 0.05.

RESULTS: Overall, the national response rate among Greek dentists was 2.5%. A total of 354 dentists across Greece participated in the study. Attendance at CPR/AED courses was recorded for 67.5% of participants, while 29.4% reported holding active certification. A small proportion of the surveyed dentists had an AED in their dental practices (8.5%), and 47.4% did not possess a self-injectable adrenaline. Syncope was the most common medical emergency during dental procedures (50.3%). Dentists who attended BLS training sessions demonstrated more appropriate practice in managing medical emergencies (P < 0.05).

CONCLUSIONS: Continuous training and ongoing professional development for dentists are essential for effectively handling medical emergencies. This study promotes a more proactive approach to enhancing competency in emergency care and the appropriate management of medical emergencies in dental practices.},
}

@article {pmid42114078,
year = {2026},
author = {Bareamichael, PI and Babu, S and Hoang, T and Socal, MP},
title = {Bridging the Funding Gap in Drug Development for Amyotrophic Lateral Sclerosis.},
journal = {Neurology. Clinical practice},
volume = {16},
number = {3},
pages = {e200623},
pmid = {42114078},
issn = {2163-0933},
mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/economics ; Humans ; *Drug Development/economics ; United States ; Clinical Trials as Topic/economics ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with few effective treatments and high clinical trial failure rates. Since 1995, only 3 drugs riluzole, edaravone, and tofersen have gained approval from the Food and Drug Administration, all offering modest benefits. Challenges in ALS drug development include poor translational preclinical models, underpowered early-phase trials, and the high cost of late-stage development. Despite federal initiatives such as the Accelerating Access to Critical Therapies for ALS Act and the ALL ALS Consortium, critical gaps remain in funding large multisite trials and sustaining research networks. Accelerating progress requires strengthening national registries, expanding adaptive trial platforms, integrating existing networks, and adopting innovative funding models such as milestone-based public-private partnerships and reinvestment of licensing revenues. A coordinated, sustainable research and funding ecosystem could transform ALS therapy development and serve as a model for advancing treatments for other rare neurodegenerative and neurogenetic disorders.},
}

*Amyotrophic Lateral Sclerosis/drug therapy/economics
Humans
*Drug Development/economics
United States
Clinical Trials as Topic/economics

@article {pmid42114311,
year = {2026},
author = {Shubham, and Mathur, A},
title = {Comment on "profiling mitochondrial DNA indices across whole blood, plasma, and CSF in amyotrophic lateral sclerosis".},
journal = {Journal of the neurological sciences},
volume = {487},
number = {},
pages = {125920},
doi = {10.1016/j.jns.2026.125920},
pmid = {42114311},
issn = {1878-5883},
}

@article {pmid42114427,
year = {2026},
author = {Ritu, JR and Uddin, MH and Ferrari, MCO and Chivers, DP},
title = {Ecotoxicological implications of environmental neurotoxin β-N-methylamino-L-alanine (BMAA) in fishes: An emerging concern.},
journal = {Ecotoxicology and environmental safety},
volume = {318},
number = {},
pages = {120252},
doi = {10.1016/j.ecoenv.2026.120252},
pmid = {42114427},
issn = {1090-2414},
abstract = {Harmful algal blooms (HABs), intensified by climate change, eutrophication, and altered hydrological regimes, are expanding globally, releasing cyanotoxins that threaten aquatic ecosystems and human health. β-N-methylamino-L-alanine (BMAA), a non-protein amino acid with neurotoxic potential, has been recognized as a global emerging concern. Following exposure, BMAA is present in both free and protein-bound forms, forming an endogenous toxin reservoir that exacerbates potential neurotoxicity in aquatic organisms and humans. Its presence in aquatic food webs not only elevates ecological risks for wildlife but also raises potential human health concerns, particularly its potential association with neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Alzheimer's disease, and the ALS/Parkinsonism-dementia complex. This review aims to explore current knowledge of the ecotoxicological impacts of BMAA in fishes, focusing on developmental, behavioural and cognitive perturbations, along with their mechanistic underpinnings. BMAA exposure induces developmental abnormalities, including convulsions, spinal axis malformations, pericardial edema, and altered heart rate, as well as neurodevelopmental impairments, such as reduced motor neuron length and altered neuromuscular colocalization in fishes. Additionally, BMAA exposure affects a wide array of behaviours in fishes, including motor coordination, locomotion, feeding, startle responses, anxiety-like behaviours, and cognitive performance, primarily through excitotoxicity, oxidative stress, apoptosis, metabolic disruption, neuroendocrine modulation, and dysregulated neurotransmitter signalling. Future research should focus on more environmentally relevant exposure scenarios, elucidating BMAA toxicokinetics, and investigating cyanotoxin co-exposure toxicity in fishes. Advancing integrative phenotypic endpoints and knowledge of molecular mechanisms of BMAA toxicity in aquatic organisms is essential for effective ecological risk assessments and for developing regulatory standards to safeguard aquatic ecosystems and human health.},
}

@article {pmid42115692,
year = {2026},
author = {Yada, Y and Naoki, H},
title = {Decomposing heterogeneity in disease progression speeds and pathways.},
journal = {NPJ digital medicine},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41746-026-02665-8},
pmid = {42115692},
issn = {2398-6352},
support = {JP23K16994//JSPS Grant-in-Aid for Early-Career Scientists/ ; JP24wm0625416//AMED Brain/MINDS 2.0/ ; JP25wm0625322//AMED Brain/MINDS 2.0/ ; JPMJMS2024//JST Moonshot R D-MILLENNIA Program/ ; JPMJCR25Q2//Japan Science and Technology Agency/ ; },
abstract = {Understanding why patients with the same diagnosis exhibit markedly different disease progression-some rapidly, others slowly, with distinct symptom patterns-remains a major challenge in medicine. Here, we developed a machine learning framework called DiSPAH (Disease-progression Speed and Pathway Analysis based on a Hidden Markov model) to estimate both the pathway and speed of disease progression in individual patients. DiSPAH models disease progression as continuous-time transitions among latent disease states with a patient-specific progression speed. We applied DiSPAH to longitudinal clinical scores from an amyotrophic lateral sclerosis (ALS) cohort and inferred each patient's trajectory of the latent disease states and progression speed. These dynamics were associated with baseline clinical features and enabled prediction of future course from first-visit data. Our results highlight that jointly modeling progression pathway and speed improves prediction of heterogeneous disease courses, offering a powerful tool for personalized care and research in ALS and other chronic conditions.},
}

@article {pmid42115814,
year = {2026},
author = {Fang, SY and Jih, KY and Chao, YC and Sytwu, HP and Shih, YC and Liao, YC and Lee, YC},
title = {Clinical and electrophysiological features for differentiating MMN from hand-onset ALS.},
journal = {Journal of the Chinese Medical Association : JCMA},
volume = {},
number = {},
pages = {},
doi = {10.1097/JCMA.0000000000001387},
pmid = {42115814},
issn = {1728-7731},
abstract = {BACKGROUND: Multifocal motor neuropathy (MMN) and amyotrophic lateral sclerosis (ALS) can be difficult to differentiate, particularly at early disease stages in patients with hand-onset weakness and without upper motor neuron (UMN) signs. This study aimed to identify clinical and electrophysiological features that may facilitate early distinction between MMN and ALS.

METHODS: We retrospectively analyzed the clinical, laboratory, and electrophysiological characteristics of patients diagnosed with MMN and ALS and receiving identical nerve conduction study protocol comprising extended motor stimulation.

RESULTS: One hundred and twenty-five patients (74 men and 51 women) were included, consisting of eight patients with MMN and 117 patients with ALS, including 42 with hand-onset ALS. Patients with MMN had a significantly younger mean age at symptom onset than those with ALS (43.1 vs. 58.7 years, p = 0.004). ALS patients had more severe muscle weakness, more frequent muscle atrophy and fasciculation, UMN signs, and body weight loss. Compared with both the overall ALS and the hand-onset ALS groups, MMN patients showed significantly lower serum creatine kinase (CK) level and higher serum IgM levels. Elevated CK levels were observed in approximately one-third of patients with hand-onset ALS, whereas none of the MMN patients had elevated CK. Conduction block (CB) on nerve conduction studies was more common in MMN (87.5%) than in all ALS cases (19.7%, p < 0.001) or hand-onset ALS (31.0%, p = 0.005). MMN patients more frequently exhibited definite CBs involving multiple nerves (85.7%) compared with all ALS (17.4%, p = 0.002) and hand-onset ALS (7.7%, p = 0.001) patients.

CONCLUSION: Our findings suggest that a combination of clinical features, serum CK and IgM levels, and electrophysiological evidence of CB provides valuable clues for distinguishing MMN from ALS.},
}

@article {pmid42116144,
year = {2026},
author = {Li, M and Jin, H and Meng, L and Altay, O and Yuksel, B and Zhang, C and Uhlen, M and Turkez, H and Mardinoglu, A},
title = {WBT-DC pipeline: a cross-cohort and cross-platform disease classification pipeline based on whole-blood transcriptomics.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-026-08254-3},
pmid = {42116144},
issn = {1479-5876},
abstract = {BACKGROUND: Machine-learning models based on tissue transcriptomic data are powerful tools for disease classification. However, their clinical adoption is limited by the invasive nature of tissue sampling. Furthermore, transcriptomic datasets are often affected by batch effects and gene-level noise, which compromise model generalizability across platforms and clinical cohorts.

METHODS: We developed WBT-DC (Whole Blood Transcriptomics-based Disease Classification), a computational pipeline designed to overcome these challenges. WBT-DC integrates rank-based feature extraction to mitigate batch effects with an ensemble machine-learning framework that incorporates cross-validation and hyperparameter optimization. Its performance was systematically evaluated across five independent cohorts involving 2,164 participants and three disease contexts: Crohn's disease (CD), ulcerative colitis (UC), and amyotrophic lateral sclerosis (ALS). We tested the model's robustness across RNA-sequencing and microarray platforms. Additionally, an internal rheumatoid arthritis (RA) cohort (n = 165) was utilized for real-world prospective validation.

RESULTS: WBT-DC demonstrated high accuracy, achieving ROC-AUC values of 0.90-0.94 in independent datasets when training and testing were conducted on the same platform. In cross-platform evaluations, the pipeline maintained robust performance with ROC-AUC values ranging from 0.71 to 0.84, consistently outperforming conventional gene expression-based models. In the RA validation cohort, WBT-DC achieved an ROC-AUC of 0.81, supporting its applicability in a real-world clinical setting.

CONCLUSIONS: WBT-DC provides a robust, non-invasive, and platform-agnostic framework for disease classification using whole-blood transcriptomics. By effectively addressing batch effects and platform variability, this pipeline offers a scalable solution for translating systems-level transcriptomic insights into applications.},
}

@article {pmid42116550,
year = {2026},
author = {Bae, JH and Kwak, S},
title = {Emergency department visits among patients with neuromuscular diseases receiving home mechanical ventilation: a nationwide population-based study.},
journal = {Journal of Yeungnam medical science},
volume = {43},
number = {},
pages = {32},
doi = {10.12701/jyms.2026.43.32},
pmid = {42116550},
issn = {2799-8010},
abstract = {BACKGROUND: Population-level data on emergency department (ED) utilization in patients with neuromuscular disease (NMDs) receiving home mechanical ventilation (HMV) remain limited. This study investigated the frequency, outcomes, and associated factors of ED visits using a nationwide administrative database.

METHODS: Using the Health Insurance Review and Assessment Service database, we identified patients with NMDs who received HMV between January 2016 and October 2021, based on diagnostic codes and the MM441 procedure code. ED visits and outcomes were analyzed using claims data. Associations between ED visits and tracheostomy or gastrostomy were evaluated using the chi-square test.

RESULTS: A total of 1,569 patients were identified; amyotrophic lateral sclerosis (39.7%) and muscular dystrophy (31.0%) were the most common diagnoses. During the study period, 1,009 patients (64.3%) visited the ED at least once, accounting for 5,159 visits (mean 5.1 visits per patient). Among these visits, 36% resulted in hospitalization and 3% resulted in death in the ED. ED visits were more frequent among patients with tracheostomy than in those without tracheostomy (76.6% vs. 59.0%; relative risk [RR], 1.30; 95% confidence interval [CI], 1.21-1.39; p<0.001). In contrast, patients with gastrostomy had a lower proportion of ED visits than those without gastrostomy (22.6% vs. 55.1%; RR, 0.41; 95% CI, 0.35-0.48; p<0.001).

CONCLUSION: ED utilization is common among patients with NMDs receiving HMV and is frequently associated with hospitalization, highlighting a substantial acute healthcare burden. These findings highlight the need for improved long-term respiratory care and outpatient management.},
}

@article {pmid42116584,
year = {2026},
author = {Bala, VC and Singh, MK and Kumar, A and Tiwari, SK and Gupta, AK and Chawla, R and Kumar, S},
title = {Targeting α-Synuclein: Current Strategies and Emerging Therapies for Synucleinopathies.},
journal = {Protein and peptide letters},
volume = {33},
number = {1},
pages = {258-274},
doi = {10.2174/0109298665429866260217115717},
pmid = {42116584},
issn = {1875-5305},
mesh = {Humans ; *alpha-Synuclein/metabolism/genetics/antagonists & inhibitors ; *Synucleinopathies/metabolism/therapy/drug therapy/pathology ; *Parkinson Disease/metabolism/therapy/drug therapy/pathology ; Autophagy/drug effects ; Animals ; Oxidative Stress ; },
abstract = {Alpha-synuclein (α-syn) is a crucial protein involved in the pathogenesis of Parkinson's Disease (PD) and other synucleinopathies. It is important with respect to neuron health, regulation of α-syn protein synthesis, and its degradation. Numerous cellular pathways implicated in the process of autophagy, chaperone, and proteolysis play a vital role in the maintenance of α-syn protein homeostasis. Autophagy dysfunction defeats α-syn protein accumulation and neuroinflammation, as present in dementia with Lewy bodies and sporadic PD. Oxidative stress is another key factor that intensifies α-syn protein misfolding and aggregation, thereby leading to neurodegeneration. Involvement in the treatment of α-syn related disorders includes passive and active immunization, inhibitors of protein aggregation, gene silencing technology, modulators of synaptic function, and target drug delivery systems. Other α-syn related therapy approaches include the development of a novel herbal formulation focusing on the gut-brain axis and interventions designed to enhance protein quality control. As clinical trials move forward, minimizing challenges related to the target involved, biomarkers, and patient stratification is crucial to decoding these therapies into effective management. These insights not only advance our understanding of α-syn biology but also highlight the urgency of early and multi-targeted therapeutic interventions.},
}

Humans
*alpha-Synuclein/metabolism/genetics/antagonists & inhibitors
*Synucleinopathies/metabolism/therapy/drug therapy/pathology
*Parkinson Disease/metabolism/therapy/drug therapy/pathology
Autophagy/drug effects
Animals
Oxidative Stress

@article {pmid42116599,
year = {2026},
author = {Saha, T and Vats, T and Mehan, S},
title = {Rituximab Beyond Oncology: Targeting B-Cell-Mediated Immunomodulatory Therapy in Neurodegenerative and Neuropsychiatric Disorders.},
journal = {Immunopharmacology and immunotoxicology},
volume = {},
number = {},
pages = {1-77},
doi = {10.1080/08923973.2026.2671714},
pmid = {42116599},
issn = {1532-2513},
abstract = {Neurological and neuropsychiatric disorders, including multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), and autoimmune encephalitis (AE), represent a growing global health burden due to their multifaceted pathophysiology and limited treatment options. These disorders are characterized by neuroinflammation, oxidative stress, protein aggregation, and blood-brain barrier (BBB) disruption, which contribute to neuronal damage and progressive functional decline. Emerging evidence underscores the pivotal role of B cells in driving disease progression through antibody production, antigen presentation, and cytokine release. Rituximab, a chimeric monoclonal antibody targeting CD20 on B cells, has shown promise as a potential immunomodulatory therapy for these conditions. Rituximab mediates its therapeutic effects via mechanisms including complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and induction of apoptosis. In MS, rituximab reduces pro-inflammatory cytokines, demyelination, and immune cell activity, thereby delaying disease progression. Preclinical studies suggest its neuroprotective potential in AD and PD by mitigating B-cell-mediated neuroinflammation and oxidative stress. Furthermore, rituximab demonstrates efficacy in AE, NMOSD, and MOGAD by depleting pathogenic B cells and reducing relapse rates. Despite its proven efficacy, rituximab poses risks such as hypogammaglobulinemia, infection, and infusion-related reactions, necessitating careful patient selection, continued monitoring, and optimization of dosing regimens. This review highlights rituximab's immunomodulatory mechanisms and its expanding role in neurodegenerative and neuropsychiatric disorders. While ongoing clinical trials explore its efficacy in ALS, depression, and schizophrenia, future research should focus on identifying biomarkers of treatment response, improving CNS penetration, and combining rituximab with other therapies to enhance safety and therapeutic outcomes. Rituximab's ability to target B-cell-driven pathology positions it as a promising agent in the evolving landscape of neuroimmunology.},
}

@article {pmid42116669,
year = {2026},
author = {Shimizu, T and Myojin, H and Bokuda, K and Kawazoe, T and Morishima, R and Kimura, H and Takahashi, K and Nakayama, Y},
title = {Offset Conduction Velocity Reveals Prognostic Slowing of Motor Axons in Amyotrophic Lateral Sclerosis.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70273},
pmid = {42116669},
issn = {1097-4598},
support = {25293449//Japan Society for the Promotion of Science/ ; 16H05583//Japan Society for the Promotion of Science/ ; },
abstract = {INTRODUCTION/AIMS: Slowing of motor nerve conduction is not classically regarded as a feature of amyotrophic lateral sclerosis (ALS). We introduce a novel electrophysiological parameter, offset motor conduction velocity (offset-MCV), to assess conduction in relatively slower motor axons and investigate its association with survival in ALS.

METHODS: Motor nerve conduction studies of the median and tibial nerves were performed in 145 patients with ALS and 70 healthy controls. Onset and offset latencies of compound muscle action potentials were measured, and onset- and offset-MCVs were calculated. Patients were followed until death or tracheostomy, and associations between MCV parameters and survival were analyzed.

RESULTS: Both onset- and offset-MCVs were significantly reduced in patients with ALS compared with controls for the median and tibial nerves (all p < 0.0001). Onset-MCVs were not associated with survival. In contrast, reduced offset-MCVs in both nerves were associated with short survival (log-rank test: median nerve, p = 0.009; tibial nerve, p = 0.021). Multivariate Cox regression analysis identified tibial nerve offset-MCV as an independent prognostic factor (p = 0.029).

DISCUSSION: Pathological slowing of motor nerve conduction occurs in ALS and is associated with poor survival. Offset-MCV may reflect disease-related changes in slower α-motor axons and represents a potential prognostic biomarker in ALS.},
}

@article {pmid42117108,
year = {2026},
author = {Jiang, A and Huang, Y and Que, X and Li, C and Lin, Z and Huang, W},
title = {Integrative Transcriptomics Identifies Ubiquitination-Related Genes BIRC2, COPS5, and TBK1 as Novel Biomarkers of T-Cell Dysregulation in Amyotrophic Lateral Sclerosis.},
journal = {Journal of inflammation research},
volume = {19},
number = {},
pages = {585872},
pmid = {42117108},
issn = {1178-7031},
abstract = {PURPOSE: Amyotrophic lateral sclerosis (ALS) is marked by immune dysregulation; however, the role of T cell-ubiquitination-related genes (TURGs) in its pathogenesis remains unclear. This study aimed to investigate the contribution of TURGs to T-cell dysfunction and ubiquitination imbalance in ALS.

PATIENTS AND METHODS: Differentially expressed genes were identified through analysis of bulk transcriptomes (GSE112680). CIBERSORT deconvolution and weighted gene co-expression network analysis were employed to define T-cell-associated modules. Integration with ubiquitination-related gene sets yielded T cell-ubiquitination-related differentially expressed genes (TURDEGs). Functional enrichment analysis and protein-protein interaction network construction, combined with multi-algorithm selection, facilitated the development of a risk-prediction model. Mechanistic insights were derived from Gene Set Enrichment Analysis, immune profiling, co-expression and regulatory network analyses, and drug-target prediction. Single-cell transcriptomic analysis provided insights into cellular-level pathogenic mechanisms in ALS. qPCR was used to validate core TURDEGs expression in peripheral blood samples from patients with ALS.

RESULTS: Thirty-nine TURDEGs were identified and exhibited significant enrichment in pathways related to ubiquitination, immune activation, autophagy, and NOD-like receptor signaling. BIRC2, COPS5, and TBK1 were identified as core genes. The resulting risk-prediction model demonstrated significant potential for clinical application. Immune infiltration analysis revealed positive correlations between core genes and CD4⁺ resting memory T cells, as well as negative correlations between COPS5, TBK1, and regulatory T cells. Adavosertib and MRS2211 were identified as potent modulators of TBK1 and BIRC2, respectively. Single-cell transcriptomics highlighted enhanced T cell-neutrophil interactions, suggesting a remodeling of the immune communication network in ALS. qPCR validation confirmed significantly increased expression of these genes in patients with ALS (p<0.05).

CONCLUSION: TURDEGs-mediated T cell dysfunction and ubiquitination imbalance play critical roles in ALS pathogenesis, unveiling novel biomarkers and potential personalized therapeutic targets.},
}

@article {pmid41985558,
year = {2026},
author = {Navarrete-Dechent, C and Pietkiewicz, P and Voloshynovych, M and Marghoob, AA},
title = {Authors' response to Mart et al's "Response to Navarrete-Dechent et al's 'Ultraviolet-induced fluorescent dermoscopy for the diagnosis of skin tumors: A multicenter study'".},
journal = {Journal of the American Academy of Dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaad.2026.03.104},
pmid = {41985558},
issn = {1097-6787},
}

@article {pmid42051315,
year = {2026},
author = {Nolan, M and Aryal, S and Ndayambaje, IS and Cao, M and Lee, P and Hovde, M and Yun, S and Wlaschin, J and Held, A and Beaussant, H and Wymann, B and Zong-Lee, C and Lim, SM and Jiang, X and Ramesh, N and Agra Almeida Quadros, AR and Boulos, A and Zinter, N and Salem, S and El-Tayar, L and Beccari, M and Presa, M and Jourdan Ferreras Reyes, C and Ruan, YY and Griesman, G and Aguilar, C and Hawrot, J and Wheeler, H and Melamed, Z and Kleinstiver, BP and Albers, M and Cleveland, DW and Tanzi, RE and Lutz, CM and Hubbard, RD and Kobayashi, D and Ward, M and R R Alves, C and Wainger, B and Pichon, CL and Lagier-Tourenne, C},
title = {Statins and genetic inhibition of the mevalonate pathway activate an ATF3-STMN2 regenerative program.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42051315},
issn = {2692-8205},
abstract = {Loss of neuronal regenerative capacity is a common feature of neurodegenerative disease and axonal injury, yet the transcriptional programs governing this state remain poorly defined. Stathmin-2 (STMN2), a tubulin-binding protein essential for axon maintenance and repair, is profoundly depleted following loss of nuclear TDP-43 in neurodegenerative disease. Here, we identify statins as potent inducers of STMN2 expression. Pharmacological and genetic suppression of the mevalonate pathway, and subsequent prevention of protein geranylgeranylation, restored STMN2 levels in TDP-43 deficient cells and promoted neurite growth. STMN2 induction was abrogated when using a statin analogue unable to interact with HMG-CoA reductase, and through co-administration of mevalonate or geranylgeranyl diphosphate substrates. RNA-seq revealed that statins induce a coordinated pro-regenerative transcriptional response, including activation of the AP-1 transcription factor complex gene, ATF3. Loss of ATF3 attenuated STMN2 induction in vitro, and diminished injury-induced Stmn2 upregulation in spinal motor neurons in vivo. These results demonstrate statins as modulators of ATF3 and STMN2 expression and highlight their therapeutic potential in neurodegenerative disease.},
}

@article {pmid42105306,
year = {2026},
author = {Flores, SV and Lillo, P and Briceño-Moya, J and Pedro, AP},
title = {Molecular and genetic landscape of amyotrophic lateral sclerosis in Latin America: a scoping review of pathogenic hypotheses and ancestral heterogeneity.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/21678421.2026.2668070},
pmid = {42105306},
issn = {2167-9223},
abstract = {Background: The genetic architecture of amyotrophic lateral sclerosis (ALS) has been predominantly characterized in populations of European ancestry, while Latin American populations remain underrepresented despite their complex admixture. Objective: To map the molecular hypotheses explored in ALS research conducted in Latin American populations and identify key methodological and structural gaps. Methods: A scoping review was conducted following Joanna Briggs Institute methodology and reported according to PRISMA-ScR guidelines. Searches were performed in Web of Science, Scopus, PubMed/MEDLINE, SciELO, and LILACS. Studies investigating genetic or molecular aspects of ALS or the ALS-FTD spectrum in Latin American populations were included. Data were extracted using a standardized matrix and synthesized descriptively. Results: Nineteen studies met inclusion criteria. Most were small, single-center investigations employing targeted candidate-gene approaches, predominantly focused on C9orf72 expansions and SOD1 mutations. Reported C9orf72 frequencies varied substantially across countries, indicating population-specific genetic heterogeneity. Only one study incorporated explicit ancestry inference, and no genome-wide association studies or large multicenter ALS genomic cohorts were identified. Conclusions: ALS research in Latin America remains limited, fragmented, and largely candidate-gene driven, with minimal integration of ancestry-informed approaches. The absence of large-scale genomic studies, despite existing regional sequencing capacity, highlights the need for coordinated multicenter initiatives to enable equitable implementation of precision medicine.},
}

@article {pmid42105767,
year = {2026},
author = {Sivasubramanian, R and Sterneckert, J},
title = {Restoring miRNA biogenesis in ALS: Enoxacin enhances DICER activity in a first-in-human trial.},
journal = {Molecular therapy : the journal of the American Society of Gene Therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ymthe.2026.04.040},
pmid = {42105767},
issn = {1525-0024},
}

@article {pmid42106156,
year = {2026},
author = {Wang, J and Hu, M and Meng, W and Zhang, M and Yuan, Z and Wang, F and Li, S},
title = {Suppressing isovaleric acid off-flavor in Bacillus subtilis fermentation and its consequential effects on secondary metabolism.},
journal = {Bioresource technology},
volume = {455},
number = {},
pages = {134803},
doi = {10.1016/j.biortech.2026.134803},
pmid = {42106156},
issn = {1873-2976},
abstract = {Bacillus subtilis-fermented soybean foods (BFSFs) are nutritious East Asian staples. However, off-flavors dominated by isovaleric acid (IVA), a branched-chain fatty acid, limit consumer acceptance and industrial adoption. Although leucine- and acetolactate-derived pathways have been proposed, key regulatory nodes for IVA in soymilk remain unclear. This study systematically evaluated the key gene nodes controlling IVA biosynthesis during soymilk fermentation by B. subtilis, including bcd (leucine dehydrogenase, Bcd), bkdAB (branched-chain α-keto acid dehydrogenase complex, Bkd), ptb (phosphotransbutyrylase, Ptb), and alsS (acetolactate synthase, ALS). This study utilized B. subtilis 168 (BS168) and a gene-editing approach to construct BS168 mutants lacking bkdAB and alsS, which were combined with previously generated BS168Δbcd and BS168Δptb. IVA was significantly reduced in all mutants, most markedly in BS168Δbcd (-81.85%) and BS168ΔbkdAB (-70.31%). The volatile profile shifted toward higher levels of fruity esters and alcohols and lower levels of acids and ketones, with improved sensory acceptability, particularly in BS168ΔbkdAB. Enzyme assays confirmed Bcd, Bkd, and Ptb as key pathway nodes, while ALS modulated upstream pyruvate flux toward branched-chain amino acid (BCAAs) biosynthesis. Collectively, this work genetically validates IVA pathway control in a real food matrix and shows that targeted disruption of bcd, bkdAB, and ptb is an effective strategy to suppress IVA off-flavor and improve sensory acceptability in B. subtilis-fermented soymilk, providing mechanistic targets for subsequent development and evaluation in food-grade or industrial strains.},
}

@article {pmid42107892,
year = {2026},
author = {Chen, G and Zhao, C and Wang, C and Chen, G and Shi, J and Chen, H},
title = {Microglia crosstalk with T cells in neurodegenerative diseases: pathogenesis and treatment targets.},
journal = {International immunopharmacology},
volume = {182},
number = {},
pages = {116781},
doi = {10.1016/j.intimp.2026.116781},
pmid = {42107892},
issn = {1878-1705},
abstract = {Immune cells play a central role in driving inflammation and neurodegeneration across various neurological disorders. Central nervous system (CNS)-resident microglia and infiltrating T cells represent the innate and adaptive immune systems, respectively, and have been reported to contribute to the pathogenesis of neurodegenerative diseases individually. Growing evidence suggests that the encounter between activated microglia and infiltrating T cells amplifies their neurotoxic potential. In this review, we discussed alterations in microglial phenotype and function, and the contributions of different T cell subsets in neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Multiple sclerosis (MS), Amyotrophic lateral sclerosis (ALS) and glaucoma. We emphasized the crosstalk between microglia and T cells via antigen presentation, chemotactic signals, and pro-inflammatory mediators. We also explored emerging therapeutic strategies aimed at modulating T cell and microglial responses, as well as their interactions, for the treatment of neurodegenerative diseases.},
}

@article {pmid42108848,
year = {2026},
author = {Jung, YH and Seok, HY and Kang, M and Do, YW and Park, JO and Kim, JH and Park, JS},
title = {Clinical Significance of Plasma Sphingosine-1-Phosphate Decline in Progression of Spinal and Bulbar Muscular Atrophy.},
journal = {Journal of clinical neurology (Seoul, Korea)},
volume = {22},
number = {3},
pages = {327-337},
doi = {10.3988/jcn.2025.0556},
pmid = {42108848},
issn = {1738-6586},
support = {NRF-2022R1C1C1009723/NRF/National Research Foundation of Korea/Korea ; RS-2025-25424215/NRF/National Research Foundation of Korea/Korea ; },
abstract = {BACKGROUND AND PURPOSE: Spinal and bulbar muscular atrophy (SBMA) is a rare X-linked neuromuscular disorder characterized by slowly progressive motor decline. However, there is no specific fluid marker that reflects the severity or progression of the disease. Therefore, identifying measurable markers that reflect disease progression remains a major unmet need in SBMA management.

METHODS: Plasma samples from 21 Korean patients with SBMA were collected at baseline and after 3 years. Untargeted and targeted metabolomics profiling was performed, and plasma sphingosine-1-phosphate (S1P) was the final candidate biomarker. S1P was then quantified using liquid chromatography-mass spectrometry. Associations between longitudinal S1P changes and clinical parameters, including the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), serum creatine kinase (CK), 6-minute walk test (6MWT), and forced vital capacity (FVC), were examined.

RESULTS: Plasma S1P levels significantly declined in the fast progression group over 3 years, while remaining relatively stable in the slow progression group. Longitudinal changes in plasma S1P showed weak-to-moderate positive trends with clinical measurements, including ALSFRS-R, FVC, and 6MWT, and a negative trend with serum CK at follow-up.

CONCLUSIONS: Plasma S1P represents a promising quantitative biomarker for monitoring SBMA progression. Validation in larger cohorts and mechanistic studies of S1P regulation are warranted to establish its role in clinical management.},
}

@article {pmid42111077,
year = {2026},
author = {Zhou, S and Li, X and Jiao, Y and Wu, J},
title = {Efficacy and safety of pharmacological and biological therapies for amyotrophic lateral sclerosis: a network meta-analysis.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1754716},
pmid = {42111077},
issn = {1664-2295},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder for which disease-modifying treatment options remain limited. This study aimed to systematically assess the efficacy and safety of pharmacological and biological therapies for ALS via a network meta-analysis (NMA).

METHODS: PubMed, EMBASE, Cochrane, and Web of Science were searched until February 25, 2025. Randomized controlled trials (RCTs) evaluating any pharmacological or biological intervention in ALS were eligible. Risk of bias was assessed using the Cochrane RoB 2 tool. A Bayesian NMA was performed in R (gemtc package). Effect estimates were expressed as mean differences (MDs) or risk ratios (RRs) with 95% credible intervals (CrIs). Interventions were ranked using the surface under the cumulative ranking curve (SUCRA). Publication bias was explored with funnel plots (Stata 18.0). Subgroup analyses were conducted for drug classes demonstrating significant efficacy and including at least three RCTs.

RESULTS: 109 trials involving 16,353 participants were included. The primary outcome was the ALS Functional Rating Scale-Revised (ALSFRS-R); secondary outcomes included forced vital capacity (FVC), mortality, and serious adverse events (SAEs). Compared with placebo, the combination of cell therapy and neuroprotective agents produced the greatest attenuation of ALSFRS-R decline (MD: 3.65, 95% CrI: 1.27-6.05) and was associated with the lowest SAE risk. Receptor agonists ranked highest for preservation of FVC, whereas alkaloids ranked first for mortality reduction; however, no intervention demonstrated a statistically significant survival benefit versus placebo. Within-class subgroup analyses further identified several specific agents, such as masitinib, talampanel, and EH301, as demonstrating relatively consistent efficacy, although substantial heterogeneity remained among enzyme inhibitors.

CONCLUSION: Cell therapy combined with neuroprotective agents may slow functional decline in ALS. Receptor agonists may help preserve respiratory function. Survival benefits remain inconclusive, underscoring the continued importance of comprehensive supportive care.

https://www.crd.york.ac.uk/PROSPERO/view/CRD420251000672, identifier CRD420251000672.},
}

@article {pmid42111176,
year = {2026},
author = {Li, Y and Yao, Z and Song, Z and Yang, P and Huang, J and Lei, K and Xu, Y},
title = {The intrinsic disorder challenge for AlphaFold: A case study of G3BP1 and pathogenic peptide.},
journal = {iScience},
volume = {29},
number = {5},
pages = {115737},
pmid = {42111176},
issn = {2589-0042},
abstract = {The dipeptide repeat protein GR20 in amyotrophic lateral sclerosis (ALS) exerts neurotoxicity in part by binding to the stress granule protein G3BP1 and disrupting liquid-liquid phase separation (LLPS). However, the structural basis of this interaction remains elusive due to the pervasive intrinsic disorder in both partners. Here, we combine biochemical assays and structure prediction to characterize the G3BP1-GR20 complex. GR20 has high-affinity binding to G3BP1 and modulates LLPS in a concentration-dependent manner. Since the standard AlphaFold (AF) pipeline failed to predict credible models, we employed a constraint-based method AFEX to generate a G3BP1-GR20 complex model with improved confidence and structural plausibility. Our work underscores the necessity of extra efforts for AF predictions on disordered complexes and demonstrates the value of integrative and knowledge-guided approaches for exploring the "invisible proteome" of biomolecular condensates.},
}

@article {pmid42112660,
year = {2026},
author = {Kasper, E and Lehto, A and Jürs, A and Nordmann, N and Peters, O and Hellmann, J and Priller, J and Spruth, EJ and Petzold, GC and Voigt, I and Weydt, P and Bernsen, S and Dinter, E and Falkenburger, B and Günther, R and Düzel, E and Glanz, W and Synofzik, M and Beichert, L and Spottke, A and Wagner, M and Brosseron, F and Schmid, MC and Halle, A and Herms, J and Schneider, A and Teipel, S and Prudlo, J and Neumann, M and Hermann, A},
title = {Alzheimer's Disease Co-Pathology and Cognitive Impairment in Amyotrophic Lateral Sclerosis.},
journal = {Annals of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ana.78227},
pmid = {42112660},
issn = {1531-8249},
abstract = {OBJECTIVES: Amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) share neuropathological features, including tau, amyloid, and TDP-43 pathology. This study investigated whether AD-related pathological changes are associated with cognitive impairment ALS.

METHODS: Cerebrospinal fluid (CSF total-tau, phosphorylated-tau, beta-amyloid) and plasma biomarkers (TDP-43; neurofilament light chain [NfL]) were analyzed in 192 individuals with ALS or ALS with frontotemporal dementia (ALS-FTD) and 100 healthy controls. Cognitive performance was assessed using the Edinburgh Cognitive and Behavioral ALS Screen (ECAS). Group comparisons and regression analyses examined associations between biomarker profiles and cognitive status. Autopsy data were available for a subset of participants.

RESULTS: Compared with healthy controls, patients with ALS - particularly those with cognitive impairment (ALSci) or ALS-FTD - showed elevated AD-related biomarkers. Significant differences in beta-amyloid levels were observed between healthy controls (HCs) and patients with ALSci, but not between controls and cognitively unimpaired patients. CSF p-tau and total-tau levels were strongly associated with domain-specific cognitive performance. In contrast, plasma extracellular vesicle TDP-43 and NfL showed weak or no association with cognition. In vivo biomarkers alone reliably distinguished cognitive impairment only in ALSci and ALS-FTD. Postmortem analyses showed no strong association between ABC scores or overall TDP-43 burden and cognitive state; however, temporal and hippocampal TDP-43 burden was associated with cognitive dysfunction.

INTERPRETATION: Our findings suggest that tau-related CSF biomarkers, particularly p-tau and total-tau, are associated with cognitive deficits in ALS, indicating that AD-related pathology might be associated to cognitive decline in ALS. However, postmortem data showed even stronger relation of TDP43 pathology to cognitive deficits in ALS. ANN NEUROL 2026 ANN NEUROL 2026.},
}

@article {pmid42112934,
year = {2026},
author = {Melechovsky, J and Novotny, M and Tykalova, T and Klempir, J and Herremans, D and Rusz, J},
title = {Development of an Interpretable Deep Learning-Based Segmentation Algorithm for Automated Assessment of Oral Diadochokinesis in Progressive Neurological Diseases.},
journal = {Journal of speech, language, and hearing research : JSLHR},
volume = {},
number = {},
pages = {1-17},
doi = {10.1044/2026_JSLHR-25-00453},
pmid = {42112934},
issn = {1558-9102},
abstract = {PURPOSE: We aimed to develop a universal, fully automated segmentation algorithm that allows robust analysis of oral diadochokinesis across various neurological diseases, dysarthria types, and dysarthria severities.

METHOD: Recordings of sequential motion rates were collected from 231 subjects, including 80 healthy controls and 151 patients with neurological diseases such as amyotrophic lateral sclerosis, essential tremor, Huntington's disease, multiple sclerosis, multiple system atrophy, Parkinson's disease, progressive supranuclear palsy, and cerebellar ataxia. A robust automatic segmentation algorithm utilizing convolutional neural networks and rule-based postprocessing was developed and evaluated across disease type, dysarthria type, and dysarthria severity. The performance of the developed artificial intelligence-based algorithm was compared with a traditional signal processing-based segmentation approach.

RESULTS: Our deep learning-based algorithm was able to correctly identify the position of individual syllables with a very high F1 score of 99.1%, compared to a signal processing-based approach with an F1 score of 97.7%. Using a 10-ms tolerance window, the deep learning-based algorithm achieved an average accuracy of 92.0% for the temporal detection of individual phoneme positions. Performance was strongly influenced by dysarthria severity, with accuracy reaching 94.7% in mild, 91.0% in moderate, and 83.1% in severe dysarthria. Disease and dysarthria type did not appear to have a substantial effect on algorithm performance.

CONCLUSIONS: Our proposed deep learning-based algorithm provides reliable segmentation of syllable and individual phoneme positions during oral diadochokinesis across various disease types, dysarthria types, and dysarthria severities. The deep learning-based segmentation approaches have the potential to outperform the traditional signal processing methods for assessing oral diadochokinesis.},
}

@article {pmid42113315,
year = {2026},
author = {Mishra, R and Upadhyay, A},
title = {Exosomes in Amyloid Propagation-Roles in Neurodegeneration.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42113315},
issn = {1559-1182},
mesh = {*Exosomes/metabolism ; Humans ; Animals ; *Neurodegenerative Diseases/metabolism/pathology ; *Amyloid/metabolism ; },
abstract = {Extracellular vesicle (EVs)-mediated cell-to-cell communication is crucial for cell growth, signaling, and metabolism. Exosomes are a subtype of EVs originating from endosomal cellular machinery and have a relatively smaller size (30-150 nM). They carry nucleic acids, proteins, miRNA, lipids, metabolites, and growth factors, making them an exciting research tool for understanding the pathophysiology of complex human diseases. Different brain cells also communicate with themselves by the release of exosomes which helps in overall brain growth and in cell signaling. Recent studies have highlighted the importance of exosomes in neurodegenerative diseases (NDDs) of Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), prion, and Huntington's disease (HD). Exosomes are involved in the spread of amyloid-like protein aggregates formed in these diseases, but a comprehensive understanding of this spread mechanism is limited. In this article, we have analyzed the roles of exosomes in the spread of amyloid protein aggregates in the NDDs. Furthermore, we have discussed possible measures to address several gaps in our current understanding of cross talks between exosomes and protein aggregates in neurodegenerative disorders (NDDs). We have also discussed the therapeutic opportunities to delay or prevent pathogenic amyloid aggregate spread by exploiting exosomal transport. Overall, the review will contribute to develop a better understanding vesicular transport of amyloids and will help contend their propagation in different NDDs.},
}

*Exosomes/metabolism
Humans
Animals
*Neurodegenerative Diseases/metabolism/pathology
*Amyloid/metabolism

@article {pmid42113599,
year = {2026},
author = {Ravits, J and Ferrey, D and Gundogdu, B and Qayoumi, W and Zale, C},
title = {Amyotrophic Lateral Sclerosis: A Review.},
journal = {JAMA},
volume = {},
number = {},
pages = {},
doi = {10.1001/jama.2026.6385},
pmid = {42113599},
issn = {1538-3598},
abstract = {IMPORTANCE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive weakness due to degeneration of upper motor neurons in the brain and lower motor neurons in the brainstem and spinal cord. It affects approximately 25 000 individuals in the United States.

OBSERVATIONS: Amyotrophic lateral sclerosis is characterized by progressive painless muscle weakness that typically begins in a focal region of the body, such as limb muscle weakness causing hand weakness or foot drop (65%), cranial muscle weakness causing speech or swallowing problems (20%-25%), or axial muscle weakness causing bent posture (5%-10%), and spreads to other body regions over time. The disease usually manifests with dysfunction indicative of both upper motor neurons (causing muscle stiffness and spasticity) and lower motor neurons (causing weakness, fasciculations, atrophy, and flaccidity). After onset, weakness spreads through the musculature and typically causes death due to respiratory muscle weakness. Among people with ALS, approximately 85% have sporadic ALS, which is not associated with known environmental or genetic factors, and 15% have familial ALS. Amyotrophic lateral sclerosis is diagnosed based on clinical features, which can be supported by results of electromyography. More than 60 genes have been associated with ALS, and most are autosomal dominant. Pathogenic variants in chromosome 9 open reading frame 72 (C9orf72) are found in 40% of all familial ALS cases, and pathogenic variants in superoxide dismutase 1 (SOD1) are found in 20% of patients with familial ALS. Patients with ALS survive a mean of 3 to 5 years after diagnosis, and there are currently no curative therapies. Clinical care primarily focuses on symptom management and quality of life. Three US Food and Drug Administration (FDA)-approved disease-modifying therapies are available in the United States. Riluzole and edaravone are oral medications that slow ALS progression by up to 2 to 4 months, and tofersen is an intrathecally administered gene therapy for patients with SOD1 gene variants. Specialized multidisciplinary teams, comprising neurologists, nurses, therapists, dietitians, and social workers, are associated with improved survival (4-7 months) and quality of life.

CONCLUSIONS AND RELEVANCE: Amyotrophic lateral sclerosis is a progressive and fatal neurodegenerative disorder of upper and lower motor neurons. No curative therapies exist. Two oral medications, riluzole and edaravone, are approved by the FDA and modestly decrease disease progression in sporadic ALS. Tofersen, an intrathecally administered gene-based therapy, is also FDA approved and slows disease progression in patients with SOD1 pathogenic gene variants.},
}

@article {pmid42102284,
year = {2026},
author = {Ma, T and Wu, F and Lou, Y and Li, X and Jin, K and Wang, X and Xu, P and Shi, Z and Xu, B},
title = {Enhancing Thermoelectric Performance through Semiconductor-Semimetal Heterostructure via Entropy- and Enthalpy-Driven Phase Regulation in Al/S-Doped BiSbSe3.},
journal = {ACS nano},
volume = {},
number = {},
pages = {},
doi = {10.1021/acsnano.6c00746},
pmid = {42102284},
issn = {1936-086X},
abstract = {This study presents a phase-regulation strategy for enhancing the thermoelectric performance of BiSbSe3-based materials through the controlled formation of a semiconductor-semimetal heterostructure. By incorporating sulfur and aluminum dopants, a hexagonal phase is induced within an orthorhombic BiSbSe3 matrix, thereby establishing a bidirectionally adjustable phase composition through compositional regulation. The hexagonal phase exhibits semimetallic behavior, with a Fermi level positioned higher than that of the semiconductor matrix. This electronic structure difference is consistent with low-barrier interfacial charge transfer and a modulation-doping-like redistribution of electrons across the phase boundaries, contributing to enhanced carrier concentration without severely sacrificing carrier mobility. Moreover, the inherently low thermal conductivity of both phases, combined with enhanced phonon scattering at the interfaces and simultaneous control over grain refinement during phase regulation, effectively suppresses the lattice thermal conductivity. The resulting biphasic structure enables coupled regulation of electronic and thermal transport, synergistically improving thermoelectric performance, achieving a peak thermoelectric figure of merit (zT) of 1.50 at 773 K in Bi0.98Sb0.98Al0.04Se2.8S0.2 under the fixed 2 wt % CuI donor-additive condition. This improvement relative to BiSbSe3 materials demonstrates the effectiveness of phase engineering in decoupling electrical and thermal transport properties. These results highlight interface-engineered semiconductor-semimetal heterostructures as an effective design route for high-performance thermoelectric materials.},
}

@article {pmid42102977,
year = {2026},
author = {Zhang, J and Wang, C and Li, Y and Xiao, Z and Cai, Z and Qian, Y and Shi, L and Zhang, Q},
title = {Lipid Dysregulation as a Central Contributor of Neurodegenerative Diseases: Emerging Therapeutic Targets and Strategies.},
journal = {Ageing research reviews},
volume = {},
number = {},
pages = {103159},
doi = {10.1016/j.arr.2026.103159},
pmid = {42102977},
issn = {1872-9649},
abstract = {Lipid homeostasis is essential for preserving the structural integrity and functional capacity of the brain. A diverse array of lipids, including cholesterol, phospholipids, and sphingolipids, has been identified as playing pivotal roles. Dysregulation of lipid metabolism is increasingly recognized as a central pathological mechanism in neurodegenerative diseases, including Alzheimer's Disease, Parkinson's Disease, Amyotrophic Lateral Sclerosis, Huntington's Disease, and Cerebrotendinous Xanthomatosis, though much of the existing evidence comes from associative studies, and causal relationships still need to be further validated through interventional studies. Here we systematically review the metabolic pathways and regulatory networks of major brain lipids, with a focus on delineating disease-specific alterations and summarizing emerging therapeutic strategies targeting lipid metabolism. These strategies encompass the modulation of cholesterol homeostasis, sphingolipid metabolism, phospholipid signaling, and fatty acid oxidation, alongside approaches that enhance lipid clearance and neural repair. Preclinical advances and ongoing clinical trials underscore the translational potential of lipid-targeted interventions. In conclusion, we emphasize the potential of lipid metabolism as a promising avenue for developing novel treatments, offering insights to guide future research and therapeutic innovation in neurodegeneration.},
}

@article {pmid42103041,
year = {2026},
author = {López-Blanch, R and Oriol-Caballo, M and Estrela, JM and Obrador, E},
title = {Multimodal strategies for diagnosis, stratification, and therapeutic monitoring in ALS.},
journal = {Neuroscience and biobehavioral reviews},
volume = {},
number = {},
pages = {106727},
doi = {10.1016/j.neubiorev.2026.106727},
pmid = {42103041},
issn = {1873-7528},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder of motor neurons (MN) that is currently diagnosed through a prolonged process of exclusion, often delaying intervention. This review provides an overview of fluid, imaging, electrophysiological, and genetic biomarkers, explicitly linking each modality to early detection, patient stratification, disease monitoring, therapeutic development, and clinical trial design. Fluid biomarkers (i.e., neurofilament light chain, phosphorylated neurofilament heavy chain, inflammatory cytokines, microRNAs, and proteins in blood or cerebrospinal fluid) reflect neuronal injury and/or disease activity, enabling early identification of pres-ymptomatic individuals and longitudinal tracking of neurodegeneration. Imaging biomarkers, such as structural and diffusion MRI of the motor cortex, corticospinal tracts, and spinal cord, as well as PET imaging neuroinflammation or metabolism, provide objective measures of MN degeneration and extra-motor involvement. Electrophysiological biomarkers, including high-density electromyography, motor unit number, transcranial magnetic stimulation, and electrical impedance myography, quantitatively assess upper and lower MN loss and functional reserve. Genetic biomarkers, encompassing variants in genes such as C9orf72, SOD1, FUS, and TARDBP, enable presymptomatic screening and molecular stratification. In this context, transposable elements have emerged as an additional layer linking genomic variation and RNA dysregulation. We highlight the importance of multimodal and stage-specific biomarker integration to improve diagnostic accuracy and illuminate distinct disease phases. This approach supports stratification by progression rate or molecular subtype, enrichment of clinical trial cohorts, and the development of surrogate endpoints. We conclude by discussing current challenges, including disease heterogeneity and assay standardization, and outline future directions toward biomarker-driven precision medicine in ALS.},
}

@article {pmid42104039,
year = {2026},
author = {Jantrapirom, S and Sangphukieo, A and U-On, N and Poonsawas, P and Wongkumool, W and Yeewa, R and Panto, C and Poound, P and Zito, E and Marrazza, A and Lo Piccolo, L},
title = {Discovery of a pyrazolopyridine alkaloid that mitigates neuronal ER stress and age-related decline.},
journal = {Communications biology},
volume = {},
number = {},
pages = {},
doi = {10.1038/s42003-026-10226-8},
pmid = {42104039},
issn = {2399-3642},
support = {FF66/061//Chiang Mai University (CMU)/ ; FF67/044//Chiang Mai University (CMU)/ ; FF68/207569//Chiang Mai University (CMU)/ ; 66-124//Health Systems Research Institute (HSRI)/ ; 68-060//Health Systems Research Institute (HSRI)/ ; N42A670768//National Research Council of Thailand (NRCT)/ ; 139/2567//CMU | Faculty of Medicine, Chiang Mai University/ ; },
abstract = {Endoplasmic reticulum (ER) stress contributes to the pathogenesis of neurodegenerative and age-associated diseases, motivating the search for compounds that enhance ER-stress resilience. Modulation of ER-redox pathways, including those associated with the oxidase ERO1A, can attenuate maladaptive unfolded protein response (UPR) signaling and improve cellular stress tolerance. Here we develop an integrative discovery strategy to identify natural compounds that mitigate ER-stress-associated phenotypes across cellular and organismal models. Structure-informed virtual screening guided by ERO1A biology prioritized the pyrazolopyridine alkaloid S88. In human SH-SY5Y-derived neurons, S88 improves survival and reduces tunicamycin-induced ER-stress markers. In Drosophila, S88 ameliorates neuromuscular and locomotor phenotypes in a UBQLN2-associated ALS model and improves aging-related outcomes. Biochemical assays did not detect inhibition of ERO1A or radical scavenging activity by S88, indicating that its molecular target remains to be identified. Together, these findings identify S88 as a natural-product scaffold that enhances ER-stress resilience across neuronal and in vivo models.},
}

@article {pmid42096854,
year = {2026},
author = {De Avila-Arias, M and Fang, L and Hoyos-Hoyos, V and Harris Ricardo, J and Cadena-Cruz, C and Villarreal-Camacho, JL and Fortich Mesa, N},
title = {Candida-bacteria interactions in peri-implantitis: A narrative review of evidence, mechanisms, and clinical implications.},
journal = {Archives of oral biology},
volume = {188},
number = {},
pages = {106603},
doi = {10.1016/j.archoralbio.2026.106603},
pmid = {42096854},
issn = {1879-1506},
abstract = {OBJECTIVE: To critically synthesize clinical, molecular, and mechanistic evidence on the contribution of the oral mycobiome, particularly Candida albicans, to peri-implantitis, and to evaluate how fungal-bacterial interactions influence biofilm pathogenicity, host responses, and potential therapeutic implications.

DESIGN: Narrative review of peer-reviewed studies including clinical and epidemiological investigations, molecular analyses (quantitative polymerase chain reaction [qPCR] and next-generation sequencing [NGS] targeting the internal transcribed spacer [ITS] region for fungal profiling and the 16S ribosomal RNA [16S rRNA] gene for bacterial profiling), in vitro and in vivo interkingdom biofilm models, and immunological mechanistic studies. Evidence was evaluated qualitatively, with emphasis on detection methods, study design, and translational relevance.

RESULTS: Molecular studies detect Candida spp. in a notable fraction of peri-implantitis sites, with higher detection by qPCR/NGS than by culture. Co-occurrence of C. albicans with periodontopathogens (e.g., Porphyromonas gingivalis, Fusobacterium nucleatum) is frequently reported. Mechanistic studies show that C. albicans forms hyphal scaffolds, consumes oxygen to create microanaerobic niches, mediates bacterial adhesion via Als adhesins, and participates in metabolic exchange and cooperative proteolysis. These processes enhance biofilm resilience, promote inflammatory signalling pathways (nuclear factor kappa B [NF-κB] and mitogen-activated protein kinase [MAPK]), activate the NLRP3 inflammasome, and increase antimicrobial tolerance. No randomized controlled trials of antifungal or interkingdom-directed therapies are currently available.

CONCLUSIONS: Evidence supports an interkingdom, polymicrobial model of peri-implantitis in which fungi contribute to biofilm stability and inflammation. However, heterogeneity in definitions, sampling, and detection methods limits causal inference. Longitudinal and interventional studies are required before mycobiome-directed therapies can be recommended.},
}

@article {pmid42096942,
year = {2026},
author = {Mazidi, M and Yong, JL and Grafton, B and MacLeod, C},
title = {Indexing automatic attentional capture by negative information in anxiety using the talking heads attentional bias assessment task.},
journal = {Behaviour research and therapy},
volume = {202},
number = {},
pages = {105066},
doi = {10.1016/j.brat.2026.105066},
pmid = {42096942},
issn = {1873-622X},
abstract = {The Talking Heads Attentional Bias Assessment Task is a recently developed, freely available, methodology for assessing anxiety-linked attentional bias to ecologically relevant emotionally negative information. The task employs video-based stimuli conveying emotionally negative or benign information concerning issues that individuals commonly encounter in daily life. It utilizes a dual-probe methodology with the aim of indexing the degree to which viewers' attention is automatically captured by the more negative videos. When introducing this task, Mazidi et al. (2025) demonstrated that the resulting attentional bias index i. has excellent internal consistency; ii. is significantly correlated with trait anxiety; and iii. mediates the association between trait anxiety and the state anxiety elevation elicited by the emotional videos. However, this prior study did not verify that the anxiety-linked attentional bias indexed by this task is automatic, in the sense that it is independent of volitional viewing preference. The present study was designed to determine the replicability of Mazidi et al.'s original findings, while overcoming this prior limitation. A sample of 170 undergraduate students completed a variant of the Talking Heads Attentional Bias Assessment Task, that now included an additional condition designed to directly measure volitional viewing preference. All of the three effects described above were replicated in full. Moreover, the association between trait anxiety and the resulting index of attentional bias was independent of volitional viewing preference. These findings attest to the capacity of this task to yield a psychometrically appropriate index of trait anxiety-linked bias in automatic attentional capture by emotionally negative information.},
}

@article {pmid42097156,
year = {2026},
author = {Gürcan, BA and Gelisken, F and Wenzel, DA and Wenzel, CJ},
title = {[Bilaterale neurosensorische Abhebung als alleinige Manifestation einer posterioren Skleritis].},
journal = {Klinische Monatsblatter fur Augenheilkunde},
volume = {},
number = {},
pages = {},
doi = {10.1055/a-2871-6976},
pmid = {42097156},
issn = {1439-3999},
}

@article {pmid42097486,
year = {2026},
author = {Deloncle, R},
title = {Conjecture for a free radical epimerization process in Alzheimer, Parkinson, Lewy body, amyotrophic lateral sclerosis, progressive Supranuclear Palsy and Creutzfeldt Jakob diseases.},
journal = {Experimental neurology},
volume = {},
number = {},
pages = {115812},
doi = {10.1016/j.expneurol.2026.115812},
pmid = {42097486},
issn = {1090-2430},
abstract = {Brain protease-resistant misfolded proteins have been described in Alzheimer (AD), Parkinson (PD), Lewy Body (LBD), Amyotrophic Lateral Sclerosis (ALS), Progressive Supranuclear Palsy (PSP) and Creutzfeldt Jakob (CJD) diseases. The role of free radicals in generating these protease resistant structures has been experimentally demonstrated in prion bovine spongiform encephalopathy (BSE), when manganese is substituted for copper (Cu), in bovine brain homogenates in reductive medium, while Cu protective effect against free radicals can be restored by Cu supplementation in oxidative medium. These facts can suggest a free radical-induced epimerization process in neuroprotein misfolding leading to the transformation of physiological L-amino acid brain proteins into abnormal D-structures which will be deposited in the brain as observed in neurodegenerative diseased brains. A blood Cu increase, not ceruloplasmin (CP) bound correlated with a Cu increase in the cerebrospinal fluid (CSF) and a Cu decrease in the brain have been described in AD, PD, ALS, or CJD. This indicates that following neuronal death, Cu might be expelled from brain proteins and subsequent to redistribution between brain, CSF and blood, it will result a brain Cu deficiency and a decrease in Cu brain protection against free radicals. In the aim of repairing this deficiency and slow down the neurodegenerative disease process, a brain Cu complexes vectorization through the blood-brain barrier might restore brain Cu homeostasis.},
}

@article {pmid42099046,
year = {2026},
author = {Yang, X and Taghavi, A and Akahori, Y and Pedrini, M and Ishii, T and Disney, MD},
title = {An RNA-Focused DNA-Encoded Library Platform for Discovering Ligands of Pathogenic r(G4C2)[exp] RNA.},
journal = {ACS chemical biology},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschembio.6c00337},
pmid = {42099046},
issn = {1554-8937},
abstract = {Disease-associated RNAs are increasingly recognized as promising therapeutic targets for small-molecule intervention. While DNA-encoded libraries (DELs) have long been established for protein ligand discovery, recent studies have demonstrated their feasibility for identifying RNA-binding small molecules. To further advance RNA-targeted ligand discovery, a diverse, solid-phase DEL enriched in privileged RNA-binding scaffolds was constructed and applied to identify ligands of r(G4C2)[exp], a toxic RNA repeat expansion implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). DEL selection outcomes were analyzed through large-scale molecular docking integrated with physicochemical and structure-activity relationship (SAR) analyses. Correlations were observed between docking predictions and experimental enrichment trends, supporting lead identification. The lead compound was subsequently optimized based on rational design, resulting in analogues with enhanced binding affinity and bioactivity. These findings demonstrate that RNA ligand identification can be effectively achieved by combining DNA-encoded library technology with computational approaches for rational design and analysis and highlight a broadly adaptable platform for RNA-targeted small-molecule discovery.},
}

@article {pmid42099104,
year = {2026},
author = {Oriquat, G and Jasim, IK and Gajjar, TB and Hanumanthayya, M and Abdulhameed Ahmad, I and Singh, G and Maharana, L and Bainsal, N},
title = {SUMOylation in Neural Health and Disease: From Cellular Homeostasis to Neurodegeneration.},
journal = {DNA and cell biology},
volume = {},
number = {},
pages = {10445498261444640},
doi = {10.1177/10445498261444640},
pmid = {42099104},
issn = {1557-7430},
abstract = {Neurodegenerative diseases (NDDs) represent a growing global health burden, particularly in aging populations. These disorders primarily affect neurons and are characterized by progressive neuronal dysfunction and loss within specific regions of the central nervous system. Major NDDs include Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, multiple sclerosis, and stroke. Although each disorder exhibits distinct genetic backgrounds and pathological protein aggregates, they share common pathogenic mechanisms, including chronic neuroinflammation, impaired autophagy and mitophagy, disrupted proteostasis, telomere instability, and epigenetic alterations. A hallmark feature across NDDs is the accumulation of misfolded proteins, leading to synaptic dysfunction and neuronal degeneration. Small ubiquitin-like modifiers (SUMOs) are a family of ∼100 amino acid proteins, including SUMO1 and the closely related SUMO2/3 isoforms. SUMOylation is a dynamic posttranslational modification that regulates protein function through the covalent attachment or removal of SUMO moieties. This reversible process is mediated by SUMO-specific E1 activating, E2 conjugating, and E3 ligating enzymes and is counterbalanced by SUMO/Sentrin-specific proteases. The SUMOylation status of target proteins depends on the tightly controlled balance between conjugation and deconjugation systems. Acting as a molecular switch, SUMOylation modulates diverse cellular processes such as DNA damage repair, RNA metabolism, transcriptional regulation, and protein quality control, all of which are essential for maintaining cellular homeostasis. Accumulating evidence links dysregulated SUMOylation to the pathogenesis of multiple neurological disorders, including polyglutamine and synucleinopathies. SUMOylation influences neuroinflammation, oxidative stress, protein aggregation, neuroangiogenesis, ischemic injury, and demyelination. This review highlights recent advances in understanding the role of SUMOylation in NDDs and explores its potential as a promising therapeutic target.},
}

@article {pmid42099653,
year = {2026},
author = {Zhang, W and Zhao, Y and Ge, N and Hou, F and Li, X and Zhao, C and Fei, H and Shi, X and Wang, W and Wang, S and Liu, X},
title = {Pediatric diamond-blackfan anemia after hematopoietic stem cell transplantation complicated by bronchiolitis obliterans and air-leak syndrome leading to lung transplantation: a case report with multimodal follow-up.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1782188},
pmid = {42099653},
issn = {1664-3224},
mesh = {Humans ; Female ; Child ; *Anemia, Diamond-Blackfan/therapy ; *Bronchiolitis Obliterans/etiology/surgery ; *Lung Transplantation/methods ; Follow-Up Studies ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Syndrome ; *Lung Diseases/etiology/surgery ; Treatment Outcome ; },
abstract = {INTRODUCTION: Bronchiolitis obliterans syndrome (BOS) is a severe, often fatal pulmonary manifestation of chronic graft-versus-host disease (cGVHD) following allogeneic hematopoietic stem cell transplantation (HSCT). Its progression to air-leak syndrome (ALS) signifies a critical deterioration with exceedingly high mortality. Lung transplantation (LTx) remains a rare salvage option, especially in children, with scarce reports of successful outcomes in those with this complication cascade.

CASE PRESENTATION: We report the case of a 7-year-old girl with Diamond-Blackfan anemia (DBA) who developed BOS complicated by ALS after allo-HSCT. She developed acute GVHD involving the skin and liver on +100d, which improved following immunosuppressive therapy. On +231d, pulmonary function tests showed severe mixed ventilatory dysfunction (FEV1 37% of predicted value, FEV1/FVC 52%), and high-resolution computed tomography (HRCT) revealed mosaic perfusion and bronchial wall thickening, contributing to the diagnosis of BOS. Despite intensive immunosuppressive therapy, she developed ALS on +360d and type II respiratory failure on +475d. Sequential bilateral LTx was performed on October 28, 2025. Postoperatively, the patient recovered following the management of multidrug-resistant bacterial infections and respiratory complications, with no rejection or recurrence of cGVHD during follow-up.

CONCLUSION: This report presents the youngest documented DBA case of successful LTx for BOS complicated by ALS after allo-HSCT globally. It demonstrates that dynamic multimodal monitoring is crucial for early BOS detection. LTx is a viable therapy for end-stage pulmonary cGVHD in children. This case underscores the need for proactive monitoring in high-risk patients and provides a paradigm for managing this complex complication.},
}

Humans
Female
Child
*Anemia, Diamond-Blackfan/therapy
*Bronchiolitis Obliterans/etiology/surgery
*Lung Transplantation/methods
Follow-Up Studies
*Hematopoietic Stem Cell Transplantation/adverse effects
Syndrome
*Lung Diseases/etiology/surgery
Treatment Outcome

@article {pmid42101064,
year = {2026},
author = {Chae, J and Yoo, SH and Lee, SY and Kim, JS and Sung, JJ and Choi, SJ},
title = {Factors Impacting Tracheostomy Decisions in Korean Individuals With Amyotrophic Lateral Sclerosis: A Cross-Sectional Survey.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70270},
pmid = {42101064},
issn = {1097-4598},
support = {RS-2025-02216164//Korea Health Industry Development Institute/Republic of Korea ; RS-2025-02215165//Korea Health Industry Development Institute/Republic of Korea ; RS-2025-00553428//National Research Foundation of Korea/ ; },
abstract = {INTRODUCTION/AIMS: Decisions regarding tracheostomy are often made under emergent circumstances, although they require complex considerations of patient preferences, quality of life, and prognosis. This study investigated decision-making surrounding tracheostomy in Korean people with amyotrophic lateral sclerosis (pwALS) and factors influencing these decisions.

METHODS: Eighty participants were recruited from the Korean ALS Association and categorized into those who underwent tracheostomy-invasive ventilation (TIV) and those who did not. Participants completed the Hospital Anxiety and Depression Scale (HADS), the Decisional Conflict Scale (DCS), and the Control Preference Scale (CPS), as well as 27 modified questions from the Columbia University TIV study assessing demographics, disease characteristics, preferences, and reasons for undergoing or declining tracheostomy.

RESULTS: Forty-two patients underwent TIV. The TIV and non-TIV groups were similar in age and sex, whereas disease duration was longer in the TIV group. Among those in the non-TIV group, King's stage 4a was the most frequent (n = 13). Fourteen patients (33%) who underwent TIV reported that they received information about tracheostomy at the time of the procedure, whereas 22 patients in the non-TIV group (58%) reported no prior discussion. DCS and HADS scores did not differ significantly between groups; however, high decisional conflict (DCS ≥ 25) was associated with higher HADS scores.

DISCUSSION: Tracheostomy decision-making among Korean pwALS is frequently crisis-driven, limiting opportunities for advance discussion. Timely and structured discussions about end-of-life care are essential for supporting informed, preference-aligned decisions and reducing psychological burden. Using simple, validated questionnaires may help identify decisional uncertainty and clarify patients' preferred roles in decision-making.},
}

@article {pmid42101470,
year = {2026},
author = {Panchal, D and Solanki, D and Solanki, R and Yadav, AK and Bhatia, D and Yadav, P},
title = {Biomaterials and Nanoparticle-Based Therapeutics in Neurodegenerative Diseases: Bridging the Gap Between Innovation and Translation.},
journal = {ACS chemical neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschemneuro.6c00245},
pmid = {42101470},
issn = {1948-7193},
abstract = {Neurodegenerative diseases, including Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, and multiple sclerosis, represent a growing global health crisis characterized by irreversible neuronal loss, protein aggregation, chronic neuroinflammation, and mitochondrial dysfunction. Central to their therapeutic intractability is the blood-brain barrier (BBB), a highly selective neurovascular interface that excludes nearly 98% of conventional pharmacological agents from the central nervous system (CNS). Nanoparticle- and biomaterial-based delivery platforms have emerged as promising strategies to overcome these barriers, encompassing liposomes, polymeric nanoparticles, engineered exosomes, inorganic nanoparticles, and hydrogel scaffolds capable of enabling targeted CNS drug delivery. This Review systematically evaluates the landscape of nanomaterial-based neurotherapeutics across disease-specific pathological contexts, critically analyzing translational failure mechanisms including limited parenchymal brain exposure, receptor saturation during transcytosis, protein corona-mediated immune clearance, and nanoscale toxicity in postmitotic neural tissue. Preclinical-to-clinical translational gaps arising from interspecies BBB transporter heterogeneity and pharmacokinetic divergence are examined alongside manufacturing and regulatory barriers impeding Good Manufacturing Practice (GMP)-scale production. Emerging convergence strategies─including AI-integrated design, hybrid physiologically based pharmacokinetic modeling, theranostic nanoplatforms, and wearable bioresponsive delivery systems─are evaluated for their capacity to address these limitations. The review concludes by proposing a framework for developing clinically viable, disease-modifying CNS nanomedicines.},
}

@article {pmid42102048,
year = {2026},
author = {Bombaci, A and Giordano, A and Lavalle, I and Magnino, A and Calvo, A and Chiò, A and Cicolin, A},
title = {"Silent Echoes of the Day: Dream Content Analysis in Amyotrophic Lateral Sclerosis".},
journal = {Brain and behavior},
volume = {16},
number = {5},
pages = {e71387},
doi = {10.1002/brb3.71387},
pmid = {42102048},
issn = {2162-3279},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/psychology/physiopathology ; Female ; Male ; Middle Aged ; *Dreams/psychology/physiology ; Aged ; Adult ; Aggression/psychology ; },
abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the degeneration of upper and lower motor neurons, leading to muscle atrophy, weakness, and respiratory failure. Numerous studies evaluated the impact of diseases on dream content, and the dream content analysis may be considered an interesting tool in the study of the internalization of the consequences of significant life changes. The study of ALS patients' dream content has been mostly neglected in the literature. This study investigated the dream content in a population affected by ALS.

MATERIAL AND METHODS: We evaluated all consecutive outpatients referred to our ALS Centre using a weekly diary of dreams. Dream contents were coded according to the Hall and Van de Castle coding system.

RESULTS: Sixty-eight patients completed the study. We collected 127 dreams (females 39.4%) (males 60.6%). Males showed a reduced presence of friends, anatomical elements, aggression, friendship, and sexuality. Instead, we found an increased presence of family members, situations in which the dreamer initiates aggressive action and familiar settings. In the female sample, we found a decreased presence of friends, aggressive and friendly elements, sex-related content, and misfortune, while an increase in animal content.

CONCLUSIONS: Our results demonstrate that dream content in ALS patients differs from that of healthy subjects, and we noticed some gender differences among ALS patients. The dream content can offer insights into ALS patients' mental state and may improve clinicians' ability to support their patients during their therapeutic course.},
}

Humans
*Amyotrophic Lateral Sclerosis/psychology/physiopathology
Female
Male
Middle Aged
*Dreams/psychology/physiology
Aged
Adult
Aggression/psychology

@article {pmid42102258,
year = {2026},
author = {Di Pede, F and Cabras, S and Manera, U and Vasta, R and Zocco, G and Minerva, E and Matteoni, E and De Mattei, F and Pellegrino, G and Palumbo, F and Pascariu, D and Callegaro, S and Maccabeo, A and Polverari, G and Martino, A and Giuliani, A and Moglia, C and Calvo, A and Chiò, A and Pagani, M and Canosa, A},
title = {King's stages of amyotrophic lateral sclerosis: an 18F-FDG-PET study of brain connectivity.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awag159},
pmid = {42102258},
issn = {1460-2156},
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting upper and lower motor neurons. TDP-43 proteinopathy is the neuropathological signature of the disease, and 18F-FDG-PET serves as a marker of neurodegeneration in vivo. The aim of the present cross-sectional study was to disentangle 18F-FDG-PET correlates of disease severity assessed through the King's staging system, by exploring connectivity changes across motor stages. ALS patients classified as King's stage 1, 2 and 3, who underwent brain 18F-FDG-PET at diagnosis from 2008 to 2022 at the ALS Centre of Turin, were included. A multiple regression analysis to evaluate the relationship between brain metabolism and King's stage was performed. The clusters showing significant results were used as seed regions in an inter-regional correlation analysis (IRCA), performed for each stage. Out of a total of 832 ALS patients, 337 were classified as King's stage 1, 274 as stage 2, and 221 as stage 3. The three groups significantly differed in age at PET, disease duration and total ALSFRS-R score at the time of PET, C9ORF72 status, and the distribution of cognitive categories. We found a decreasing metabolic gradient from King's stage 1 to King's stage 3 in a cluster encompassing motor and cognitive areas. As King's stage increases, we found a decrease of connectivity within the sensorimotor and cognitive areas. The IRCA also showed the connectivity of motor and cognitive regions with temporal and cerebellar regions. The connectivity with temporal regions found in King's stage 1 decreases in King's stage 2 and finally disappears in King's stage 3. The connectivity with the cerebellum occurs in King's stage 2 and decreases in King's stage 3. The changes of connectivity of motor and cognitive areas with temporal and cerebellar regions among different King's stages might reflect the spread of TDP-43 proteinopathy or a compensatory mechanism, respectively. The present study suggests that 18F-FDG-PET imaging of the brain may be integrated with King's staging system to assess the extent of the pathogenic process in the context of clinical trials.},
}

@article {pmid42091241,
year = {2026},
author = {Pronto-Laborinho, AC and Carvalho, M},
title = {Interleukin-6 in ALS: metabolic mediator or marker of ventilatory decline?.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-2},
doi = {10.1080/21678421.2026.2667283},
pmid = {42091241},
issn = {2167-9223},
}

@article {pmid42091714,
year = {2026},
author = {Motta, S and Quaremba, G and Aruta, L and Allosso, S and Senerchia, G and Iuzzolino, VV and Dubbioso, R},
title = {The Dysphagia Outcome and Severity Scale (DOSS) and non-instrumental swallowing measures in amyotrophic lateral sclerosis.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {6},
pages = {},
pmid = {42091714},
issn = {1590-3478},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications/diagnosis/physiopathology ; *Deglutition Disorders/diagnosis/etiology/physiopathology ; Male ; Female ; Middle Aged ; Aged ; *Severity of Illness Index ; Reproducibility of Results ; Deglutition/physiology ; Adult ; ROC Curve ; },
abstract = {PURPOSE: To evaluate reliability of the Dysphagia Outcome and Severity Scale (DOSS) in Amyotrophic Lateral Sclerosis (ALS) patients, and to assess diagnostic accuracy of selected non-instrumental measures in defining swallowing safety in this population.

METHODS: One hundred and thirteen consecutive ALS patients underwent comprehensive dysphagia evaluation with fiberoptic endoscopic evaluation of swallowing (FEES) and were classified according to DOSS. Safe and unsafe swallowing were defined by DOSS levels 7-6 and 5-1, respectively. Patient-reported measures included ALS Functional Rating Scale-Revised swallow item (I-3) and Eating Assessment Tool-10 (EAT-10). Non-instrumental clinical measures were hyolaryngeal excursion, voluntary cough (VC), voice quality and reflexive cough/throat clearing (VRC), and maximum phonation time (MPT). Inter- and intra-rater reliability were assessed using weighted Cohen's kappa and Fleiss' kappa coefficients. Non-instrumental measures diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis.

RESULTS: Twenty-six of 113 patients (23%) exhibited an unsafe swallowing. Inter- and intra-rater agreement for DOSS classification was excellent across raters. EAT-10 and a composite clinical index derived from VC, VRC, and MPT showed the highest diagnostic accuracy with area under the curve values of 0.790 and 0.832, respectively. Other non-instrumental measures demonstrated lower discriminative performance.

CONCLUSIONS: The DOSS showed an excellent reliability when applied to FEES in patients with ALS, supporting its use as a functional classification tool with direct nutritional and management implications. Non-instrumental measures should be interpreted with caution and confined to a triage role rather than diagnostic decision-making, particularly in light of the rapid progression of dysphagia in ALS.},
}

Humans
*Amyotrophic Lateral Sclerosis/complications/diagnosis/physiopathology
*Deglutition Disorders/diagnosis/etiology/physiopathology
Male
Female
Middle Aged
Aged
*Severity of Illness Index
Reproducibility of Results
Deglutition/physiology
Adult
ROC Curve

@article {pmid42091757,
year = {2026},
author = {Puthusseri, SP and Ravivarma, S and Johny, M and Vengellur, A},
title = {Hypoxia-inducible factor-1α: Dual roles in maintaining neuronal homeostasis and neuronal degeneration via regulation of oxidative stress, mitochondrial dynamics, and bioenergetics.},
journal = {Journal of physiology and biochemistry},
volume = {82},
number = {1},
pages = {},
pmid = {42091757},
issn = {1877-8755},
mesh = {*Hypoxia-Inducible Factor 1, alpha Subunit/metabolism/genetics ; Humans ; *Oxidative Stress ; Energy Metabolism ; Animals ; *Neurons/metabolism/pathology ; *Mitochondrial Dynamics ; *Mitochondria/metabolism/pathology ; Homeostasis ; *Nerve Degeneration/metabolism/pathology ; },
abstract = {Hypoxia-inducible factor-1α (HIF-1α) is an oxygen-sensitive transcription factor with an inherently paradoxical biology: under mild-to-moderate hypoxic stress, it functions as a pro-survival regulator, yet under severe or prolonged hypoxia, the same signalling axis promotes apoptotic and autophagic cell death. This duality carries particular significance in neurons, where HIF-1α serves as a critical nexus among neuronal survival, metabolic adaptation, and mitochondrial integrity, and where the consequences of its dysregulation are most profound given their exceptional metabolic demands and limited regenerative capacity. This review examines the molecular determinants governing this protective-to-detrimental switch, integrating key interconnected dimensions: the context-dependent regulation of oxidative stress, the control of mitochondrial bioenergetics, dynamics, mitophagy, and axonal transport; the dual role of HIF-1α in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and cerebral ischemia; and the therapeutic implications of precision-targeted HIF-1α modulation. Across all these contexts, a consistent pattern emerges: early or acute HIF-1α activation is broadly neuroprotective, while chronic or severe hypoxic stress converts the same pathway into a driver of neurodegeneration. Understanding the determinants of this switch, including hypoxia duration, severity, and cell-type specificity, provides a framework for designing temporally precise therapeutic interventions for hypoxia-related neurological disorders.},
}

*Hypoxia-Inducible Factor 1, alpha Subunit/metabolism/genetics
Humans
*Oxidative Stress
Energy Metabolism
Animals
*Neurons/metabolism/pathology
*Mitochondrial Dynamics
*Mitochondria/metabolism/pathology
Homeostasis
*Nerve Degeneration/metabolism/pathology

@article {pmid42092055,
year = {2026},
author = {Azizzadeh, M and Wouters, EFM and Karimi, A and Janssen, DJA and Spaetgens, B and Hartl, S and Breyer-Kohansal, R and Breyer, MK},
title = {Integration of lung function in allostatic load scoring and its impact on mortality prediction.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-48880-x},
pmid = {42092055},
issn = {2045-2322},
abstract = {Allostatic load refers to the physiological "wear and tear" that results from adaptation to stressors over the lifespan. In this study, we integrated lung function (LF) parameters into the calculation of the allostatic load score (ALS) to evaluate changes in its performance for predicting all-cause mortality. Data from 8,775 participants (aged 25-82 years; 52% female) who participated in the first wave of the Austrian LEAD cohort were used. "ALS without LF" was calculated using 12 parameters, including cardiovascular, metabolic, body composition, and bone mineral density measures. Z-scores of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were integrated with the aforementioned parameters for the calculation of "ALS with LF". Participants scored 1 point for each at-risk marker and 1 point for medication use for hypertension, diabetes, and dyslipidaemia. The total points constituted the ALS. Participants were followed-up for death for an average of 7.7 years. The association of ALS, with and without LF, with mortality was investigated using Cox proportional hazards models. ALS increased with age and was higher in males compared to females across all age categories. ALS (as a continuous variable) with LF [hazard ratio (HR): 1.19 (95% confidence interval (CI) 1.14-1.24)] and without LF [HR: 1.16 (95% CI 1.11-1.21)] showed a significant association with mortality in sex- and age-adjusted models. The adjusted models incorporating ALS as a categorical variable showed that individuals with high ALS, with [HR: 2.44 (95% CI 1.41-4.20)] and without [HR: 2.47 (95% CI 1.46-4.80)] LF parameters, had a higher risk of mortality compared to those in the low ALS group. Cox models incorporating "ALS with LF" parameters exhibited higher concordance index and R[2] values, along with a lower Akaike's information criterion indicating superior predictive power compared to models that included "ALS without LF". ALS is strongly associated with mortality, with higher ALS linked to an increased risk of mortality across both continuous and categorical analyses. Models that incorporate ALS with LF parameters demonstrated superior predictive performance and greater robustness, underscoring the added value of including LF in the models.},
}

@article {pmid42092406,
year = {2026},
author = {Chen, Q and Zhou, Y and Peng, Y and Lan, J and Kang, Y and Wu, L and Liu, J and Tang, J and Peng, Y},
title = {TRIM16 attenuates TDP43-mediated oxidative injury by coordinating Nrf2 activation and TFR1 autophagic degradation.},
journal = {Free radical biology & medicine},
volume = {252},
number = {},
pages = {132-149},
doi = {10.1016/j.freeradbiomed.2026.05.014},
pmid = {42092406},
issn = {1873-4596},
abstract = {TAR DNA-binding protein 43 (TDP43) aggregation is a well-established pathological hallmark of amyotrophic lateral sclerosis (ALS) and related neurodegenerative disorders, contributing significantly to oxidative stress and neuronal injury. Here, we report that the M337V mutation in TDP43 exacerbates its proteotoxicity relative to the wild-type protein. Concurrently, multi-omics analysis revealed a pronounced downregulation of TRIM16 in motor neuron-like cells expressing either wild-type or M337V mutant TDP43. Functional studies demonstrated that TRIM16 overexpression effectively mitigated oxidative stress, restored mitochondrial integrity, and suppressed ferroptosis. Mechanistically, TRIM16 promoted the ubiquitination and degradation of Keap1, thereby facilitating the activation of Nrf2-mediated antioxidant genes. Furthermore, we identified the iron import receptor TFR1 as a novel ubiquitination substrate of TRIM16. TRIM16 mediated the ubiquitination of TFR1 and targeted it for p62-dependent autophagic degradation, which in turn reduced iron accumulation and lipid peroxidation. Collectively, our findings establish TRIM16 as a pivotal suppressor of TDP43-induced toxicity by orchestrating dual cytoprotective pathways to enhance cellular resilience, highlighting its promising therapeutic potential for TDP43 proteinopathy.},
}

@article {pmid42092970,
year = {2026},
author = {Liu, H and Hu, C and Liu, H and Gong, Z and Jiang, S and Xie, J and Li, Y and Liu, C and Wang, Y and Zou, C and Yang, G},
title = {Mechanistic insights and therapeutic potential of targeting the cGAS-STING pathway in neurodegenerative diseases.},
journal = {Journal of neuroinflammation},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12974-026-03815-1},
pmid = {42092970},
issn = {1742-2094},
support = {2023JJ40952//the Natural Science Foundation of Hunan Province/ ; 2024JJ6618//the Natural Science Foundation of Hunan Province/ ; 82204733//Foundation for Innovative Research Groups of the National Natural Science Foundation of China/ ; 20254677//Health Research Project of Hunan Provincial Health/ ; 82474009//the National Natural Science Foundation of China/ ; },
abstract = {The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is a central cytosolic DNA-sensing module that links DNA damage and mitochondrial dysfunction to innate immune activation. Here, we focus on canonical cGAS-STING signaling in the central nervous system (CNS) and discuss non-canonical branches only when directly relevant to neurodegeneration. We summarize structural and activation-termination mechanisms and synthesize cell-type-biased outputs across microglia, astrocytes, neurons, and oligodendroglial lineage cells. We then integrate Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease by mapping shared DNA-stress triggers to multicellular amplification loops and by grading causal evidence from genetic perturbation, pharmacological pathway interference, and correlative human datasets. Finally, we classify inhibitor modalities and emerging enabling technologies while emphasizing translational constraints, including blood-brain barrier (BBB) delivery, long-term safety, human STING-allele diversity, and pharmacodynamic biomarkers. Collectively, we propose an evidence-calibrated framework for judging when cGAS-STING is most plausibly positioned as a causal node, a permissive amplifier, or a secondary correlate in neurodegenerative disease, and where therapeutic translation should proceed cautiously.},
}

@article {pmid42093061,
year = {2026},
author = {Abbasi, H and Rasekhi, H and Shafaatdoost, M and Mohajerani, A and Asadollahi, M and Rashidi, M and Malekahmadi, M and Sarraf, P},
title = {Association of dietary inflammatory index with body composition and disease progression in adults with amyotrophic lateral sclerosis: evidence from a cross-sectional study.},
journal = {BMC nutrition},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40795-026-01336-x},
pmid = {42093061},
issn = {2055-0928},
support = {IR. TUMS.NI.REC.1401.059//Tehran University of Medical Sciences and Health Services/ ; },
abstract = {BACKGROUND: For decades, diet's pro-inflammatory properties have been considered a potential risk factor in the onset of amyotrophic lateral sclerosis (ALS). This study aimed to explore the association of dietary inflammatory index (DII) with body composition and disease progression in adult individuals with ALS.

METHODS: Clinically stable adults aged 18 years and older were enrolled for this study from the neuromuscular disorders clinic at Imam Khomeini Hospital. All participants met the EI Escorial criteria for ALS. Participants completed a 153-item dish-based semi-quantitative food frequency questionnaire (FFQ), which was developed and validated for Iranian adults. Multiple linear regression analyses were performed to examine the association between DII and the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R), Medical Research Council (MRC) score, disease progression rate (DPR), and body composition among adult participants with ALS.

RESULTS: This cross-sectional study involved 93 adult participants with ALS, comprising 29 women and 64 men (aged 56.95 ± 12.05 years). Participants in the third DII tertile had significantly reduced consumption of several nutrients, comprising vitamin E (P < 0.001), vitamin A (P < 0.001), vitamin B6 (P < 0.001), folic acid (P = 0.006), vitamin K (P < 0.001), fluoride (P = 0.009), potassium (P < 0.05), and selenium (P = 0.003). DPR displayed a significant negative association with the third tertile of DII (βT3 vs. T1= -1.1, 95CI%:-2.2, -0.04; Ptrend= 0.04), signifying a significant relationship after accounting for confounders, including age, gender, BMI, physical activity, and history of ALS.

CONCLUSION: Our findings suggest that higher inflammatory dietary patterns might be associated with a slower rate of disease progression in adults suffering from ALS. To elucidate these findings, randomized controlled trials are warranted.},
}

@article {pmid42093242,
year = {2026},
author = {Torgeman, S and Pincot, DDA and Bjornson, M and Famula, RA and Skillin, P and Krill-Brown, A and Feldmann, MJ},
title = {Genetic architecture of angular leaf spot resistance in cultivated strawberry shaped by epistasis and genotype-by-environment interactions.},
journal = {The plant genome},
volume = {19},
number = {2},
pages = {e70246},
doi = {10.1002/tpg2.70246},
pmid = {42093242},
issn = {1940-3372},
support = {//California Strawberry Commission/ ; FI- 642-24//United States - Israel Binational Agricultural Research and Development Fund/ ; 2024-67013-42591//Agricultural Research Service/ ; 2022-51181-38328//National Institute of Food and Agriculture/ ; },
mesh = {*Fragaria/genetics/microbiology ; *Epistasis, Genetic ; *Disease Resistance/genetics ; *Plant Diseases/genetics/microbiology ; *Gene-Environment Interaction ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide ; Genotype ; Xanthomonas/physiology ; Phenotype ; Quantitative Trait Loci ; },
abstract = {Angular leaf spot (ALS), caused by Xanthomonas fragariae, is a bacterial disease that limits strawberry (Fragaria × ananassa) productivity worldwide. Although major resistance loci have been identified in wild Fragaria species, their introgression into elite germplasm remains constrained by linkage drag and inconsistent inheritance. To dissect the genetic architecture of ALS resistance, we evaluated a diverse panel of n = 241 greenhouse-tested and n = 468 field-tested strawberry accessions representing elite cultivars, breeding materials, and heirloom varieties of cultivated strawberry (F. × ananassa). Plants were evaluated under controlled inoculations and natural field infection using a standardized phenotypic scale and genotyped with 50K single nucleotide polymorphism array. Broad-sense heritability was moderate (H[2] = 0.45), whereas narrow-sense heritability was low (h[2] = 0.10), reflecting the contribution of nonadditive genetic effects such as epistasis. Genome-wide association studies (GWAS) identified two loci on chromosomes 1D and 2D, explaining 4%-5% of phenotypic variance, respectively. A segregating F1 population validated the 2D locus, confirmed by co-localization with the GWAS signal explaining 11.3% of the phenotypic variance. Two-dimensional genome wide scan in this F1 population revealed a significant epistatic interaction between locus on chromosome 2D and an additional locus on chromosome 6B, collectively explaining 27% of the phenotypic variance. Together, these results demonstrate that nonadditive effects in these populations control ALS resistance. Understanding this complexity provides a foundation for developing elite cultivars with durable resistance, such as UCD Royal Royce. Our findings underscore the need for predictive breeding strategies that capture epistatic and environmental variance to accelerate genetic gain for ALS resistance in strawberry.},
}

*Fragaria/genetics/microbiology
*Epistasis, Genetic
*Disease Resistance/genetics
*Plant Diseases/genetics/microbiology
*Gene-Environment Interaction
Genome-Wide Association Study
Polymorphism, Single Nucleotide
Genotype
Xanthomonas/physiology
Phenotype
Quantitative Trait Loci

@article {pmid42093345,
year = {2026},
author = {Griffiths, AW and White, S and Norman, P and Coates, E and Hartley, H and Williams, IA and Halliday, V and Beever, D and Hackney, G and Stavroulakis, T and , and McDermott, C},
title = {Development of a Complex Intervention to Support High Calorie Diets for People With Amyotrophic Lateral Sclerosis.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.70269},
pmid = {42093345},
issn = {1097-4598},
support = {RP-PG-1016-20006//National Institute for Health and Care Research/ ; },
abstract = {INTRODUCTION: Weight loss in people with amyotrophic lateral sclerosis (pwALS) is a poor prognostic factor. We aimed to develop an intervention to support pwALS to increase calorie intake and explore feasibility and acceptability.

METHODS: Intervention development was underpinned by the Capability, Opportunity and Motivation (COM-B) model and Person Based Approach (PBA). Phase 1: healthcare professional (HCP) focus groups (n = 47), national survey (n = 281), mapping review and National Health Service (NHS) organization Freedom of Information requests (n = 251) charted current nutritional support. Systematic reviews of correlates (65 studies) and interventions supporting nutritional behaviors (14 studies), and interviews/focus groups with pwALS (n = 18), carers (n = 18) and HCPs (n = 51) identified barriers/facilitators. Phase 2: Think Aloud interviews (verbalizing thoughts whilst using the intervention) with pwALS (n = 12), carers (n = 10) and HCPs (n = 10). Phase 3: three pilot cycles, interviews with pwALS (n = 9), carers (n = 6) and HCPs (n = 5).

RESULTS: Limited evidence-based nutritional guidelines, late dietetic referral post-diagnosis, little HCP training, and few effective interventions were identified. Key facilitators/barriers included capabilities (physical ability), opportunities (social support), and motivations (dietary beliefs). The intervention was developed and piloted to refine content, presentation, and functionality. Concerns around high calorie diets and increasing intake were addressed. The final intervention comprises: (1) interventionist training, (2) calorie target setting, (3) food diaries, (4) feedback provision, (5) online resources, and (6) oral nutritional supplements. User feedback indicates high usability, acceptability, and feasibility.

DISCUSSION: The theoretically grounded intervention targets calorie intake through tailored behavior change techniques to support dieticians in practice to deliver personalized care and oral nutritional support for pwALS.},
}

@article {pmid42093834,
year = {2026},
author = {Martinez-Nunez, AE and Guo, J and Dorsey, ER and Ruffing, KW and Wymer, J and Okun, MS},
title = {Head trauma and environment progression of amyotrophic lateral sclerosis: long-term data from the National ALS Registry.},
journal = {BMJ neurology open},
volume = {8},
number = {1},
pages = {e001574},
pmid = {42093834},
issn = {2632-6140},
abstract = {BACKGROUND: Environmental exposures have been linked to increased risk of amyotrophic lateral sclerosis (ALS); however, their impact on disease progression remains unclear. This study examined whether prior environmental and occupational exposures influenced functional decline in patients with an established ALS diagnosis.

METHODS: We conducted a retrospective cohort analysis using the National ALS Registry from 2010 to 2024. Participants with complete exposure histories were included. Disease progression was measured with the ALS Functional Rating Scale-Revised (ALSFRS-R) at baseline and every 3 months. Mixed-effects linear regression models assessed associations between exposures and ALSFRS-R decline, adjusting for age, sex and time since diagnosis.

RESULTS: The cohort included 8618 participants with ALS. The median time from diagnosis to enrolment was 2 years (IQR= 1.1-2.9), with a median of 1 year of follow-up (IQR=1-4). Exposure to herbicides (β=-0.57. IC95%=-0.86 to -0.28, p<0.001), metal dust and fumes (β=-0.28, IC95%=-0.51 to -0.04, p=0.020) and oil paint (β=-0.27, IC95%=-0.48 to -0.06, p=0.011) prior to diagnosis were each associated with accelerated decline. Head injury was associated with an overall lower ALSFRS-R score (β=-1.74, IC95%=-2.21 to -1.27, <0.001), based on our non-linear mixed effects model.

CONCLUSION: Environmental and occupational exposures, particularly herbicides, metal dust/fumes and oil-based paints, were associated with faster ALS progression, and head injury was associated with overall worse function.},
}

@article {pmid42093907,
year = {2026},
author = {Talukder, A and Kelly, M and Gray, D and Sarma, H},
title = {Addressing the double burden of malnutrition in Bangladesh: Evidence from National Policy Documents and gaps in policy integration.},
journal = {Global epidemiology},
volume = {11},
number = {},
pages = {100258},
pmid = {42093907},
issn = {2590-1133},
abstract = {Bangladesh faces a growing double burden of malnutrition (DBM), where persistent undernutrition coexists alongside rapidly rising overweight and obesity. Despite numerous national policies addressing malnutrition, the extent to which these policies explicitly recognize and integrate DBM remains unclear. Objective: This study critically analyzes major national nutrition, food security, health, and agriculture policies in Bangladesh to assess DBM integration and identify gaps requiring urgent policy attention. Methods: We conducted a narrative policy analysis of five purposively selected national policy documents on nutrition implemented between 2015 and 2030. Policies were evaluated using a structured analytical framework informed by Hawkes et al.'s double-duty actions framework, the Essential Nutrition Actions framework of the World Health Organization, and the policy principles of the Global Nutrition Report. The analysis examined three dimensions: (i) recognition and framing of DBM, (ii) intervention design and content, and (iii) implementation systems. Data were extracted using a pre-specified template, verified by a second reviewer, and compared against framework components to identify gaps. Recommendations were then classified into immediate, medium-term, and long-term priorities based on feasibility and urgency. Results: All five policies demonstrated comprehensive undernutrition programming, with measurable targets. However, overnutrition has received minimal attention in all the policies. Only the National Nutrition Policy (2015) explicitly acknowledged DBM, but this fell short of an integrated operational framework. The remaining four policies continued to treat malnutrition as synonymous with undernutrition, leaving overnutrition largely invisible as a policy concern. No policy has provided integrated service delivery models, household-level DBM strategies, life-course surveillance systems, or food environment regulations. Seven critical gap categories were identified: service delivery, monitoring and evaluation, human resources, dietary guidelines, food environment regulation, equity and targeting, and multi-sectoral coordination. Conclusions: Bangladesh's nutrition policies remain structurally misaligned with its evolving DBM burden. Urgent policy actions are needed to explicitly recognize DBM as a distinct policy problem, establish integrated operational frameworks, develop household-level strategies, strengthen food environment regulations, and build multisectoral governance capacity. Phased recommendations spanning immediate, medium-term, and long-term timeframes are proposed to guide systematic DBM policy integration and support progress toward Sustainable Development Goal targets.},
}

@article {pmid42094407,
year = {2026},
author = {Flax, R and Lacigová, A and Howell, S and Li, H and Bashore, FM and Čajánek, L and Axtman, AD},
title = {Development of Potent and Cell Active 5-Azaindole-Based Tau Tubulin Kinase Inhibitors.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.04.27.721186},
pmid = {42094407},
issn = {2692-8205},
abstract = {We have developed and characterized a potent and cell active tau tubulin kinase 1 and 2 (TTBK1 and TTBK2) inhibitor, 13 . Compound 13 demonstrates in-cell, kinome-wide selectivity, and potently inhibits both TTBK1 and TTBK2. As part of our medicinal chemistry campaign, we also identified a structurally similar negative control, compound 5 , which lacks in-cell affinity for TTBK1 and TTBK2. Based on their substrates, which include TDP-43, tau, and tubulin, TTBK1 and TTBK2 inhibition has been pursued as a therapeutic approach for Alzheimer's disease, frontotemporal lobe dementia, and amyotrophic lateral sclerosis. TTBK2 is also an effector of ciliogenesis, acting in concert with CEP164, CP110, and CEP83 to initiate the biogenesis of primary cilia. The development of selective chemical tools for these kinases facilitates investigation into TTBK1/2-mediated pathways and potential disease-altering ramifications linked to their pharmacological perturbation.},
}

@article {pmid42094412,
year = {2026},
author = {Tilahun, K and Parameswaran, J and Dudley, M and Pun, D and Ma, F and Zhang, J and Bold, T and Jiang, J},
title = {TMEM106B C-terminal fragments drive nucleocytoplasmic transport failure and TDP-43 mislocalization in the aging human brain.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.04.23.719939},
pmid = {42094412},
issn = {2692-8205},
abstract = {TMEM106B is a lysosomal membrane protein and major genetic modifier of multiple neurodegenerative diseases, including frontotemporal lobar degeneration, Alzheimer's disease, and amyotrophic lateral sclerosis. Proteolytically generated C-terminal fragments of TMEM106B assemble into amyloid fibrils that accumulate in the brains of individuals with neurodegenerative disease and in cognitively normal aged adults, yet how these fibrils produce neuronal dysfunction has remained unclear. Here, we show that cytosolic and lysosome-directed TMEM106B C-terminal fragments (CTF and gCTF) form detergent-insoluble amyloid aggregates, drive redistribution of endogenous TDP-43 from the nucleus to the cytoplasm, and accelerate neuronal death. Unbiased proximity proteomics identified the inner nuclear membrane LAP1-TorsinA axis as a fragment-specific interactome, and co-immunoprecipitation confirmed a direct physical interaction between gCTF and LAP1 that was not observed with full-length TMEM106B. Fragment expression disrupted Lamin B1 organization, mislocalized the nuclear import machinery KPNB1 and RanGAP1, and impaired importin-dependent nuclear transport in primary cortical neurons. Critically, neurons harboring endogenous TMEM106B fibrillar pathology in aged human frontal cortex exhibited the same phenotypes, namely disrupted Lamin B1 and LAP1 localization and cytoplasmic redistribution of TDP-43, whereas fibril-negative neurons from the same cases and younger control tissue retained intact nuclear envelope organization. These findings define TMEM106B proteinopathy as an upstream driver of nuclear envelope disruption and nucleocytoplasmic transport failure, linking a widespread feature of brain aging to a central mechanism of neurodegeneration.},
}

@article {pmid42095061,
year = {2026},
author = {Hu, Z and Wan, JJ and Yan, QQ and Fan, Y and Liu, J},
title = {Systematic proteomics reveals plasma NEFL as a robust predictor and pathological associate in C9ORF72-related neurodegeneration.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1792887},
pmid = {42095061},
issn = {1663-4365},
abstract = {BACKGROUND: The C9ORF72 repeat expansion is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). While neurofilament light chain (NEFL) is an established biomarker of neuroaxonal damage, its specific dose-response relationship with the C9ORF72 expansion and its potential role beyond a passive bystander require systematic investigation. We performed a proteome-wide screen to identify plasma proteins linked to the C9ORF72 expansion and evaluated their predictive value for motor neuron disease (MND).

METHODS: We utilized whole-genome sequencing and plasma proteomics from the UK Biobank, analyzing 106 individuals with C9ORF72 expansions (defined as >30 repeats) and 212 age- and sex-matched controls. We screened ~3,000 proteins for associations with the continuous repeat count. The top candidate was evaluated using restricted cubic splines (RCS) to assess non-linearity and threshold effects. Its ability to independently predict MND risk was tested using regression models and a machine learning approach.

RESULTS: Our unbiased screen identified NEFL as the sole protein significantly associated with the C9ORF72 repeat count (FDR-adjusted P = 8.39 × 10[-4]). NEFL levels demonstrated a step-wise increase with expansion size, which followed a stable linear trajectory across the repeat spectrum (P non - linear = 0.4435). Elevated NEFL independently predicted MND risk (OR = 2.42; HR = 2.90), even after adjusting for the C9ORF72 repeat count. Our predictive model, combining NEFL and repeat count, achieved an AUC of 0.941 with 100% sensitivity. These findings align with emerging evidence that secreted NEFL may actively modulate neuroinflammation.

CONCLUSIONS: NEFL emerges as a robust and specific plasma biomarker for C9ORF72-related neurodegeneration. Its strong linear association with repeat burden and independent predictive power, contextualized within its potential role in immune activation, suggest that NEFL is deeply integrated into the C9ORF72 pathological landscape. These findings support NEFL-based screening and monitoring strategies for early intervention in C9ORF72 carriers.},
}

@article {pmid42095090,
year = {2026},
author = {Tremblay, E and Arbour, D and Vallée, J and Piovesana, R and Vallières, G and Mechichi, E and Robitaille, R},
title = {Neuromuscular junction innervation and motor function are preserved by restoring muscarinic signaling in perisynaptic glia in ALS.},
journal = {iScience},
volume = {29},
number = {5},
pages = {115565},
pmid = {42095090},
issn = {2589-0042},
abstract = {Neuromuscular junction (NMJ) denervation is an early pathological event in amyotrophic lateral sclerosis (ALS) causing motor dysfunction and paralysis. Glial cells at the NMJ, perisynaptic Schwann cells (PSCs), ensure a balance between maintenance and repair via muscarinic receptor signaling. However, in ALS mouse models, PSCs show an aberrant muscarinic hyperactivation. We posited that this excessive activation impairs the PSC capacity to support NMJ repair in ALS. Beginning at symptoms onset, SOD1 [G37R] mice received daily oral administration of darifenacin, a clinically approved type 3 muscarinic receptor antagonist, to reduce PSC hyperactivation. The treatment improved locomotion and preserved NMJ innervation in male mice, with comparable effects observed in females, and extended survival in males. Functional benefits were supported by signs of glial repair and enhanced survival of lumbar motor neurons. These preclinical data indicate that pathological PSC hyperactivity contributes to NMJ denervation in ALS and support therapeutic strategies targeting NMJs in ALS.},
}

@article {pmid42095783,
year = {2026},
author = {Gupta, S and Russell, B and Kristensen, LG and de Chant, J and Lu, A and Obst-Huebl, L and Rad, B and Tyler, J and Subramanian, S and Kidd, S and Paul, S and Chen, Y and Petzold, CJ and Kahan, DN and Costello, SM and Nakamura, K and Inman, JL and MacDowell, AA and Spucces, A and Ralston, CY},
title = {Design and commissioning of a new synchrotron beamline dedicated to X-ray footprinting mass spectrometry.},
journal = {Journal of synchrotron radiation},
volume = {},
number = {},
pages = {},
doi = {10.1107/S1600577526003711},
pmid = {42095783},
issn = {1600-5775},
support = {R01GM126218//National Institutes of Health, National Institute of General Medical Sciences/ ; P30GM124169//National Institutes of Health, National Institute of General Medical Sciences/ ; },
abstract = {The structural biology method of X-ray footprinting mass spectrometry (XFMS) is available at two national synchrotron beamlines in the USA: one at the Advanced Light Source (ALS) on the West Coast and the other at the National Synchrotron Light Source II on the East Coast. XFMS is a solution-state technique that utilizes oxidative modifications of proteins at micromolar concentrations in aqueous buffer to extract structural information. X-rays are employed to generate hydroxyl radicals in situ, which covalently modify specific protein side chains. These modifications are subsequently quantified using liquid chromatography and mass spectrometry. Ratiometric changes in modification levels between two protein states (e.g. with and without ligand) generate a relative solvent accessibility map of the protein pairs, which serves to reveal structural features. Up until recently, the XFMS capability was available as part of a shared program at the ALS without a dedicated beamline. In this article, we describe the commissioning of ALS beamline 3.3.1, dedicated to XFMS, including the installation of a new focusing mirror, the design and construction of a new endstation with automated sample handling and exposure capabilities, and the use of accurate empirical dose calculations using Gafchromic film. Finally, we showcase the new beamline capabilities using two protein systems.},
}

@article {pmid42096556,
year = {2026},
author = {Copley, KE and Mauna, JC and Danielson, HL and Chen, Q and Ozguney, B and Ngo, M and Xie, L and Smirnov, A and Davis, M and Mayne, L and Linsenmeier, M and Rubien, JD and Bergmann, CA and Portz, B and Lee, BL and Odeh, HM and Lai, L and Chang, YW and Hallegger, M and Ule, J and Pasinelli, P and Poon, Y and Mittal, J and Fawzi, NL and Black, BE and Donnelly, CJ and Jensen, BK and Shorter, J},
title = {Short RNA chaperones promote aggregation-resistant TDP-43 conformers to mitigate neurodegeneration.},
journal = {Science (New York, N.Y.)},
volume = {392},
number = {6798},
pages = {eadv3301},
doi = {10.1126/science.adv3301},
pmid = {42096556},
issn = {1095-9203},
mesh = {Animals ; *DNA-Binding Proteins/chemistry/genetics/metabolism ; Humans ; *Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology ; Mice ; Motor Neurons/metabolism/pathology ; *Protein Aggregation, Pathological/genetics ; *RNA/metabolism/chemistry ; RNA Recognition Motif ; },
abstract = {Aberrant aggregation of the prion-like RNA binding protein TDP-43 drives several fatal neurodegenerative proteinopathies, including amyotrophic lateral sclerosis (ALS). In this work, we define how short, specific RNAs solubilize TDP-43. These short RNAs engage and stabilize the TDP-43 RNA recognition motifs, which allosterically destabilizes a conserved helical region in the prion-like domain, thereby promoting aggregation-resistant conformers. Sequence-space mining identified short RNA chaperones with enhanced activity against TDP-43 and disease-linked variants. Enhanced short RNA chaperones mitigated aberrant TDP-43 phenotypes in optogenetic models and in ALS patient-derived and control motor neurons. In mice with cytoplasmic TDP-43 aggregation and motor neuron loss, an enhanced short RNA chaperone reduced pathological aggregation, restored TDP-43 function, and conferred neuroprotection. These results define a mechanistic and therapeutic framework for RNA-based strategies to counter TDP-43 proteinopathies.},
}

Animals
*DNA-Binding Proteins/chemistry/genetics/metabolism
Humans
*Amyotrophic Lateral Sclerosis/genetics/metabolism/pathology
Mice
Motor Neurons/metabolism/pathology
*Protein Aggregation, Pathological/genetics
*RNA/metabolism/chemistry
RNA Recognition Motif

@article {pmid41855303,
year = {2026},
author = {Drouin, E and Pereon, Y},
title = {Historical and Clinical Analysis of a Case of Progressive Muscular Atrophy (1853-1871).},
journal = {European neurology},
volume = {},
number = {},
pages = {1-8},
doi = {10.1159/000550658},
pmid = {41855303},
issn = {1421-9913},
abstract = {BACKGROUND: Progressive muscular atrophy (PMA) emerged in the mid-19th century as a distinct clinical entity within the evolving field of French neurology, notably through the work of François Amilcar Aran, Duchenne de Boulogne, and later Jean-Martin Charcot. During this period, uncertainties persisted regarding its nosological status, pathophysiology, and relationship to amyotrophic lateral sclerosis (ALS). Longitudinal clinical observations from this era remain rare but are essential for understanding both the natural history of motor neuron diseases and the historical construction of neurological knowledge.

SUMMARY: This article presents a historical and clinical analysis of a unique case of PMA observed for over nearly 2 decades (1853-1871) in Parisian hospitals. The case concerns Auguste-Joseph Bellinghen, whose condition was first documented in an unpublished handwritten manuscript in 1853 and later published with photographic illustrations in 1871. Through a comparative analysis of these two observations, the study traces the slow, asymmetrical, and irreversible progression of muscular atrophy, marked by early fasciculations, the absence of sensory disturbances, and eventual severe motor disability. The case is examined within its institutional, nosological, and therapeutic contexts, highlighting hospital circulation, the role of medical interns, and the empirical treatments of the time, including electrotherapy and thermal baths. Reinterpreted in light of contemporary neurology, this historical observation likely corresponds to a spinal-onset motor neuron disease closely related to ALS. Beyond its clinical significance, the case illustrates the transition from descriptive clinical medicine to anatomoclinical correlation and contributes to the historiography of neurology by illuminating how individual patient trajectories shaped medical knowledge in the 19th century.

KEY MESSAGES: (1) Long-term historical clinical observations provide valuable insights into the natural history of PMA and motor neuron diseases. (2) The Bellinghen case illustrates the evolution of neurological semiology, particularly the early recognition of fasciculations and asymmetrical muscle wasting. (3) This case highlights the transition from Aran's initial clinical description of PMA to Charcot's anatomopathological framework linking PMA to ALS. (4) Historical medical archives offer not only scientific data but also a window into the social consequences of chronic neurological disease in the 19th century. (5) Integrating historical and clinical analysis enriches contemporary understanding of motor neuron disease nosology and medical memory.},
}

@article {pmid42086408,
year = {2026},
author = {Ibrahim, M and Hossain, MS and Ooi, L and Hasan, MM and Ahsan, S and Salem, AK and Piazza, GA and Feng, X and Ahsan, F},
title = {Targeting the NAD[+]-PARP1-XRCC1 axis in ALS.},
journal = {Trends in molecular medicine},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.molmed.2026.04.004},
pmid = {42086408},
issn = {1471-499X},
abstract = {Amyotrophic lateral sclerosis (ALS) remains a fatal neurodegenerative disease with few effective therapies. Emerging evidence indicates that oxidative DNA damage, defective base excision and single-strand break repair, and progressive NAD[+] depletion contribute to motor neuron degeneration. The NAD[+]-PARP1-XRCC1 axis sits at the intersection of genome maintenance and metabolic control, linking DNA damage signaling to cellular bioenergetics. When dysregulated, this pathway may drive persistent PARP1 activation, failed repair, and energetic collapse. In this review, we integrate mechanistic and translational evidence supporting this axis as a therapeutic target in ALS. We propose a staged translational framework that prioritizes repurposable low-trapping PARP1 inhibitors combined with NAD[+] support, followed by central nervous system-directed RNA-lipid nanoparticle delivery of repair factors, with poly(ADP-ribose) and NAD[+] metabolites as pharmacodynamic biomarkers.},
}

@article {pmid42086533,
year = {2026},
author = {Modafferi, S and Silenzi, V and Garbelli, A and Lazoi, G and Scarian, E and D'Uva, S and Santini, T and Riccardi, A and Cozzolino, M and Pansarasa, O and D'Ambrosi, N and Sabbioneda, S and Morlando, M and Francia, S},
title = {Proteasomal-dependent CHK1 degradation leads to DNA damage accumulation in ALS cellular model systems.},
journal = {Cell death & disease},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41419-026-08603-6},
pmid = {42086533},
issn = {2041-4889},
support = {PNRR-CN3 642 "National Center for Gene Therapy and Drugs based on RNA Technology"//Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)/ ; 2017NWEXEP//Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)/ ; 2020CXFL4T//Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)/ ; 2022R7LH5T//Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)/ ; 2022R7LH5T//Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)/ ; DN. 1553 11.10.2022//Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)/ ; 2017KSZZJW//Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)/ ; 2022JA8JY5//Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)/ ; DSB.AD004.294//Regione Lombardia (Region of Lombardy)/ ; DSB.AD004.294//Regione Lombardia (Region of Lombardy)/ ; DSB.AD004.294//Regione Lombardia (Region of Lombardy)/ ; FOE-2021 DBA.AD005.225//Consiglio Nazionale delle Ricerche (National Research Council)/ ; DBA.AD005.225-NUTRAGE-FOE2021//Consiglio Nazionale delle Ricerche (National Research Council)/ ; FOE-2021 DBA.AD005.225//Consiglio Nazionale delle Ricerche (National Research Council)/ ; RIPREI2023_7c8ae10d783c//Istituto Superiore di Sanità (ISS)/ ; IG2022-27833//Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research)/ ; IG-2020-24316//Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research)/ ; Ricerca Corrente 2025 - 2027//Ministero della Salute (Ministry of Health, Italy)/ ; Ricerca Corrente 2025 - 2027//Ministero della Salute (Ministry of Health, Italy)/ ; RG12419107CD28D5//Sapienza Università di Roma (Sapienza University of Rome)/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is characterised by the aggregation of TDP-43 and mutant FUS in the cytoplasm of affected motor neurons. Accumulation of DNA damage is emerging as a novel correlative trait of ALS. We recently showed that formation of TDP-43 and FUS cytoplasmic inclusions (CIs) lead to DNA damage accumulation through dysregulation of the DNA damage response (DDR). However, the multiple molecular mechanisms contributing to DNA damage accumulation in affected motor neurons in ALS have not been fully elucidated. In recent years, chemical inhibition of the serine/threonine kinase CHK1 was shown to lead to accumulation of DNA breaks as well as increased apoptosis, in differentiated cortical neurons. Notably, CHK1 has been involved in DNA double-strand break repair in non-dividing cells, by acting through the histone chaperone ASF1A. In this article, we show that cells bearing FUS and TDP-43 CIs show downregulation of the protein levels of CHK1 and ASF1A. We observe CHK1 protein downregulation in neuronal cell lines, as well as in patient-derived motor neurons progenitors and in the spinal cord of a FUS-ALS mouse model. Restoration of the nuclear levels of CHK1 and ASF1A via transient overexpression, is sufficient to reduce DNA damage signal accumulation and rescues DDR defects. Importantly, we show that the ubiquitin-proteasome pathway is responsible for CHK1 degradation in cells bearing FUS CI, since its inhibition restores CHK1 and ASF1A protein levels. Our study demonstrates that proteasomal-dependent CHK1 and ASF1A downregulation contributes to accumulation of DNA damage in cells affected by ALS-linked protein aggregates.},
}

@article {pmid42087223,
year = {2026},
author = {Brede, JR and Farbu, BH and Gamberini, L and Thorsen, K and Rehn, M and Rognås, L and Tønsager, K and Sunde, GA and Lauritzen, M and Lupi, C and Tartaglione, M and Skjaerseth, EÅ and Aaen, M and Wiseth, R and Krüger, AJ},
title = {Prehospital resuscitative endovascular balloon occlusion of the aorta in non-traumatic out-of-hospital cardiac arrest (REBOARREST): an international, multicentre, open label, pragmatic, randomised, controlled trial.},
journal = {Critical care (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13054-026-06057-y},
pmid = {42087223},
issn = {1466-609X},
abstract = {BACKGROUND: Most patients with out-of-hospital cardiac arrest do not achieve sustained return of spontaneous circulation (ROSC). Resuscitative endovascular balloon occlusion of the aorta (REBOA) may increase blood pressure proximal to the ballon. If this technique is used during advanced life support (ALS), and occlusion is performed in the thoracic aorta, it may augment aortic pressure and coronary perfusion pressure. We investigated whether prehospital REBOA as an adjunct to ALS increased the rate of ROSC.

METHODS: REBOARREST was a pragmatic, parallel-group, multicentre, randomised controlled trial conducted at 12 sites in Norway, Denmark, and Italy. Adult patients (18-80 years) with non-traumatic out-of-hospital cardiac arrest were randomly assigned (1:1) to either a control group that received ALS or to an intervention group that received ALS combined with REBOA as an adjunct. Fulfilment of eligibility criteria was determined by the physician on scene and sealed envelopes were used to allocate patients. The statistician that performed the analyses was blinded for group allocation. The primary outcome was sustained ROSC, defined as lasting ≥ 20 min, assessed in the intention-to-treat population.

RESULTS: From June 7, 2021, to June 28, 2025, 200 patients were randomly assigned to the study groups. Due to lack of consent 21 patients dropped out of the trial, hence data from 179 patients are presented, 88 in the intervention group and 91 in the control group. Most patients were male (76%), with median age of 68 years (IQR 58-74). Median time from arrest to randomisation was 33 min (IQR 23-39) in the intervention group and 29 min (IQR 23-38) in the control group. Twenty-five of 88 patients (28%) in the intervention group and 24 of 91 patients (26%) in the control group achieved sustained ROSC (adjusted risk difference 1.8% [-11, 15, 95% CI], p = 0.78). Adverse events were registered in 19 patients.

CONCLUSIONS: Among patients with non-traumatic out-of-hospital cardiac arrest, a strategy of prehospital deployment of REBOA as an adjunct to ALS was feasible but did not significantly improve rates of sustained ROSC compared to ALS alone. Deployment of prehospital REBOA is safe and manageable in a two-person team with low procedure time.

TRIAL REGISTRATION: Clinicaltrials.gov ID NCT04596514. Registered 22.10.2020.},
}

@article {pmid42087256,
year = {2026},
author = {Harper, NS and Sharpe, JL and Speranza, J and Gulia, R and Chen, JX and Allen, SP and Atwal, MS and Pickering-Brown, S and Livesey, MR and Bennett, CL and Prokop, A and La Spada, AR and West, RJH},
title = {Targeting the integrated stress response or Ataxin-2 alleviates neurodegeneration in PolyGR models of C9orf72 associated frontotemporal dementia and amyotrophic lateral sclerosis.},
journal = {Acta neuropathologica communications},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40478-026-02301-2},
pmid = {42087256},
issn = {2051-5960},
support = {630//Alzheimer's Society and The Heather Corrie Impact Fund/ ; Livesey/Oct20/900-792/MNDA_/Motor Neurone Disease Association/United Kingdom ; Livesey/Oct20/900-792/MNDA_/Motor Neurone Disease Association/United Kingdom ; NIH R35 NS122140//National Institutes of Health (NIH)/ ; NIH R35 NS122140//National Institutes of Health (NIH)/ ; 510/ALZS_/Alzheimer's Society/United Kingdom ; },
abstract = {Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are fatal, early-onset neurodegenerative diseases. The most common genetic cause of FTD and ALS is a G4C2 hexanucleotide repeat expansion in the C9orf72 gene. This mutation leads to the production of toxic dipeptide repeat proteins (DPRs), via repeat-associated non-AUG (RAN) translation. These DPRs disrupt stress granule (SG) dynamics, with SG regulators such as Ataxin-2 (ATXN2) implicated in disease risk. The integrated stress response (ISR), a key driver of SG formation via eIF2α phosphorylation, has been linked to C9orf72 expansions, but the role of individual DPRs in ISR activation remains unclear. Here, using Drosophila models expressing physiologically relevant repeat length DPRs, we identify poly(GR) as a novel activator of the ISR, inducing early and sustained eIF2α phosphorylation and SG accumulation prior to motor decline. Genetic inhibition of the ISR or knockdown of ATX2, the Drosophila orthologue of ATXN2, rescues motor deficits in these models. ATXN2 knockdown also reduces poly(GR) toxicity in mouse primary neurons. These findings position poly(GR) as a key driver of ISR activation and highlight ATXN2 and the ISR as promising therapeutic targets in C9orf72-associated FTD/ALS.},
}

@article {pmid42087754,
year = {2026},
author = {van Selms, MKA and Lobbezoo, F and Verhoeff, MC},
title = {[A personal exploration of oral health in amyotrophic lateral sclerosis].},
journal = {Nederlands tijdschrift voor tandheelkunde},
volume = {133},
number = {5},
pages = {232-238},
doi = {10.5177/ntvt.2026.05.26012},
pmid = {42087754},
issn = {0028-2200},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/complications ; *Oral Health ; *Oral Hygiene ; Quality of Life ; },
abstract = {Amyotrophic lateral sclerosis is a progressive neurodegenerative disease impairing motor functions, including those of the oral muscles. As a result, oral hygiene and oral care become challenging. Nonetheless, oral health in patients with amyotrophic lateral sclerosis often remains under-addressed. On the basis of interviews with Dr M.K.A. van Selms dental researcher and patient oral health in amyotrophic lateral sclerosis was explored, highlighting care, research and education. Dr van Selms identifies the neglect of oral hygiene in the care of patients with amyotrophic lateral sclerosis, and advocates for patient-informed, functionally tailored guidelines, interdisciplinary collaboration, and improved access to dental services. He also calls for ethically sensitive, patient-centred research; he stresses the relevance of inclusive training for all involved; and recommends developing instructional material for carers and patients. Dr van Selms unique perspective reveals the necessity to integrate oral health into the care for this patient group and offers starting points for improving oral health and quality of life in amyotrophic lateral sclerosis and similar diseases.},
}

Humans
*Amyotrophic Lateral Sclerosis/complications
*Oral Health
*Oral Hygiene
Quality of Life

@article {pmid42088060,
year = {2026},
author = {Hou, DL and Ho, J and Guan, T and Dong, XX and Zeng, L and Sanders, LH and Wu, YC and Tan, EK and Zhou, ZD},
title = {E3 ubiquitin ligases in neurodegenerative diseases.},
journal = {Military Medical Research},
volume = {13},
number = {1},
pages = {100032},
pmid = {42088060},
issn = {2054-9369},
mesh = {Humans ; *Ubiquitin-Protein Ligases/therapeutic use ; *Neurodegenerative Diseases/physiopathology ; },
abstract = {Neurodegenerative diseases (NDs) are characterized by progressive neuronal loss and proteostatic failure, driven by impaired clearance of misfolded proteins via the ubiquitin-proteasome system (UPS) and autophagy. In UPS, E3 ubiquitin ligases are crucial for regulating protein ubiquitination and degradation. Mutations in E3 ligases, along with dysfunctions of specific ligases such as Parkin, the C-terminus of HSC70-interacting protein (CHIP), and tripartite motif-containing proteins, have been identified as key factors in the buildup of amyloid-β, α-synuclein, tau, trans-active response DNA-binding protein 43, and mutant huntingtin. These accumulations are associated with NDs like Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. Therapeutic strategies targeting E3 ligases, particularly proteolysis-targeting chimeras (PROTACs), are being developed for ND treatment and are currently in clinical trials. These approaches aim to enhance E3 ligase activity and promote selective protein degradation. Here, we examine how individual E3 ligases influence cell-fate decisions in NDs, showing that their substrate selection determines whether neurons survive or die. Building on this knowledge, we present an innovative therapeutic pipeline that includes ligase activators, PROTAC degraders, and miRNA switches, which are molecules designed to transition from research to clinical application.},
}

Humans
*Ubiquitin-Protein Ligases/therapeutic use
*Neurodegenerative Diseases/physiopathology

@article {pmid42070188,
year = {2026},
author = {Chambers, RL and Lahuerta-Martín, S and Greco, AM and Pattinson, R and Pickles, T and Hassan, J and Mokkink, LB},
title = {Assessing content validity: challenges of conducting systematic reviews of patient-reported outcome measures and recommendations to improve the application of COSMIN guidance.},
journal = {Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation},
volume = {35},
number = {6},
pages = {},
pmid = {42070188},
issn = {1573-2649},
abstract = {PURPOSE: Systematic reviews of Patient-Reported Outcome Measures (PROMs) are essential for selecting appropriate measures for research and clinical practice. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines provide a standardised framework for evaluating measurement properties of PROMs, with content validity considered to be the most important property, yet the most complex and poorly reported. This study aimed to report common challenges researchers face when evaluating content validity in systematic reviews on the quality of PROMs, and to provide clear, experience-informed recommendations to overcome them.

METHOD: A narrative synthesis of challenges in evaluating content validity in systematic reviews of PROMs is presented. Challenges were extracted from Elsman et al.’s umbrella review and from stakeholder consultations with the authors of this manuscript, providing practical recommendations and illustrative examples.

RESULTS: Seven challenges were identified: (1) feasibility of conducting a systematic review on the quality of PROMs, (2) identifying all articles describing PROM development for the target population, (3) managing different versions of PROMs, (4) poor reporting in primary studies (5) ambiguity in classifying studies as PROM development or content validity studies, (6) applying the criteria for content validity, specifically, to the results of development studies, and (7) accurately framing the scope of the PROM and the review. Recommendations include narrowing the scope of the review, conducting supplementary searches, treating PROM versions distinctly, and guidance on how to interpret poorly reported studies.

CONCLUSION: These insights support consistent application of COSMIN guidelines and improve PROM selection and use, complementing existing COSMIN materials.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11136-026-04261-5.},
}